statistical report of the ar-calux validation study

Statistical report of the

AR-CALUX® validation study

EUR 30044 EN

This publication is a Validated Methods, Reference Methods and Measurements report by the Joint Research Centre (JRC), the European Commission’s science and knowledge service. It aims to provide evidence-based scientific support to the European policymaking process. The scientific output expressed does not imply a policy position of the European Commission. Neither the European Commission nor any person acting on behalf of the Commission is responsible for the use that might be made of this publication. For information on the methodology and quality underlying the data used in this publication for which the source is neither Eurostat nor other Commission services, users should contact the referenced source. The designations employed and the presentation of material on the maps do not imply the expression of any opinion whatsoever on the part of the European Union concerning the legal status of any country, territory, city or area or of its authorities, or concerning the delimitation of its frontiers or boundaries.

This statistical report was produced in context of the validation study of the AR-CALUX® in vitro method carried out by the JRC's EU Reference Laboratory for alternatives to animal testing (EURL ECVAM). The statistical analyses were carried out by Roman Liska on behalf of EURL ECVAM.

The AR-CALUX® test method is included in OECD Test Guideline 458 on Androgen Receptor TransActivation assays.

Contact information European Commission, Joint Research Centre (JRC), Chemical Safety and Alternative Methods Unit (F3) via E. Fermi 2749, I-21027 Ispra (VA), Italy [email protected]

EU Science Hub https://ec.europa.eu/jrc

JRC116993

EUR 30044 EN

PDF ISBN 978-92-76-15034-3 ISSN 1831-9424 doi:10.2760/587965

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© European Union, 2020

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How to cite this report:Liška, R., Statistical report of the AR-CALUX® validation study, EUR 30044 EN, Publications Office of the European Union, Luxembourg, 2020, ISBN 978-92-76-15034-3, doi:10.2760/587965, JRC116993.

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Contents

1 Introduction ................................................................................................... 1

2 Methods......................................................................................................... 2

2.1 Study design.............................................................................................. 2

2.2 Data management...................................................................................... 3

2.3 Acceptance criteria ..................................................................................... 4

2.3.1 Agonist testing...................................................................................... 4

2.3.2 Antagonist testing ................................................................................. 4

2.4 Statistical data analysis ............................................................................... 5

2.4.1 Classification for agonist properties.......................................................... 5

2.4.2 Classification for antagonist properties ..................................................... 6

2.4.3 Reproducibility ...................................................................................... 6

2.4.4 Predictive capacity................................................................................. 7

3 Results and discussion ..................................................................................... 8

3.1 Acceptance criteria ..................................................................................... 8

3.2 Test item responses .................................................................................... 12

3.3 Classifications ............................................................................................ 14

3.4 Classifications for Agonist testing: discussion ................................................. 16

3.5 Classifications for Antagonist testing: discussion............................................. 18

3.6 Reproducibility ........................................................................................... 27

3.7 Other........................................................................................................ 29

3.7.1 Potency statistics................................................................................... 29

3.7.2 Variability measures .............................................................................. 39

A Overview of accepted runs................................................................................ 41

A.1 Agonist testing........................................................................................... 41

A.2 Antagonist testing ...................................................................................... 47

B Acceptance criteria .......................................................................................... 55

B.1 Agonist testing........................................................................................... 55

B.2 Antagonist testing ...................................................................................... 65

C Responses - Agonist ........................................................................................ 75

C.1 Test item 1 ............................................................................................... 76

C.2 Test item 2 ............................................................................................... 79

C.3 Test item 3 ............................................................................................... 82

C.4 Test item 4 ............................................................................................... 85

C.5 Test item 5 ............................................................................................... 88

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C.6 Test item 6 ............................................................................................... 91

C.7 Test item 7 ............................................................................................... 94

C.8 Test item 8 ............................................................................................... 97

C.9 Test item 9 ...............................................................................................100

C.10 Test item 10 .............................................................................................103

C.11 Test item 11 .............................................................................................106

C.12 Test item 12 .............................................................................................109

C.13 Test item 13 .............................................................................................112

C.14 Test item 14 .............................................................................................115

C.15 Test item 15 .............................................................................................118

C.16 Test item 16 .............................................................................................121

C.17 Test item 17 .............................................................................................124

C.18 Test item 18 .............................................................................................127

C.19 Test item 19 .............................................................................................130

C.20 Test item 20 .............................................................................................133

C.21 Test item 21 .............................................................................................136

C.22 Test item 22 .............................................................................................137

C.23 Test item 23 .............................................................................................138

C.24 Test item 24 .............................................................................................139

C.25 Test item 25 .............................................................................................140

C.26 Test item 26 .............................................................................................141

C.27 Test item 27 .............................................................................................142

C.28 Test item 28 .............................................................................................143

C.29 Test item 29 .............................................................................................144

C.30 Test item 30 .............................................................................................145

C.31 Test item 31 .............................................................................................146

C.32 Test item 32 .............................................................................................147

C.33 Test item 33 .............................................................................................148

C.34 Test item 34 .............................................................................................149

C.35 Test item 35 .............................................................................................150

C.36 Test item 36 .............................................................................................151

C.37 Test item 37 .............................................................................................152

C.38 Test item 38 .............................................................................................153

C.39 Test item 39 .............................................................................................154

C.40 Test item 40 .............................................................................................155

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C.41 Test item 41 .............................................................................................156

C.42 Test item 42 .............................................................................................157

C.43 Test item 43 .............................................................................................158

C.44 Test item 44 .............................................................................................159

C.45 Test item 45 .............................................................................................160

C.46 Test item 46 .............................................................................................161

C.47 Test item 3 (2) ..........................................................................................162

D Responses - antagonist ....................................................................................163

D.1 Test item 1 ...............................................................................................164

D.2 Test item 2 ...............................................................................................170

D.3 Test item 3 ...............................................................................................174

D.4 Test item 4 ...............................................................................................180

D.5 Test item 5 ...............................................................................................186

D.6 Test item 6 ...............................................................................................192

D.7 Test item 7 ...............................................................................................198

D.8 Test item 8 ...............................................................................................202

D.9 Test item 9 ...............................................................................................206

D.10 Test item 10 .............................................................................................212

D.11 Test item 11 .............................................................................................218

D.12 Test item 12 .............................................................................................222

D.13 Test item 13 .............................................................................................226

D.14 Test item 14 .............................................................................................230

D.15 Test item 15 .............................................................................................236

D.16 Test item 16 .............................................................................................242

D.17 Test item 17 .............................................................................................246

D.18 Test item 18 .............................................................................................252

D.19 Test item 19 .............................................................................................258

D.20 Test item 20 .............................................................................................264

D.21 Test item 21 .............................................................................................270

D.22 Test item 22 .............................................................................................271

D.23 Test item 23 .............................................................................................273

D.24 Test item 24 .............................................................................................275

D.25 Test item 25 .............................................................................................277

D.26 Test item 26 .............................................................................................278

D.27 Test item 27 .............................................................................................280

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D.28 Test item 28 .............................................................................................281

D.29 Test item 29 .............................................................................................282

D.30 Test item 30 .............................................................................................283

D.31 Test item 31 .............................................................................................285

D.32 Test item 32 .............................................................................................287

D.33 Test item 33 .............................................................................................288

D.34 Test item 34 .............................................................................................289

D.35 Test item 35 .............................................................................................291

D.36 Test item 36 .............................................................................................292

D.37 Test item 37 .............................................................................................294

D.38 Test item 38 .............................................................................................296

D.39 Test item 39 .............................................................................................297

D.40 Test item 40 .............................................................................................299

D.41 Test item 41 .............................................................................................301

D.42 Test item 42 .............................................................................................303

D.43 Test item 43 .............................................................................................305

D.44 Test item 44 .............................................................................................307

D.45 Test item 45 .............................................................................................309

D.46 Test item 46 .............................................................................................310

D.47 Test item 3 (2) ..........................................................................................312

References .........................................................................................................314

List of abbreviations and definitions .......................................................................314

List of figures......................................................................................................315

List of tables.......................................................................................................321

iv

1 Introduction

The AR-CALUX® in-vitro method was developed by BioDetection Systems B.V. (BDS) com- pany to determine agonistic or antagonistic properties of chemicals. The method measures their ability to stimulate/inhibit the transcription of a luciferase reporter gene by binding to the androgen receptor.

More precisely, the AR-CALUX® is a human cell line(human osteosarcoma cell line U2-OS) based in-vitro assay, that provides information on the ability of chemicals to activate the human androgen receptor, leading to transcription. The cell line constitutively expresses the human androgen receptor (hAR). The activated hAR translocate to the nucleus, bind to the responsive elements after which the cell produces luciferase as a response. The amount of luciferase can be determined by adding the substrate luciferin and measuring the amount of light produced. The amount of light is directly proportional to the amount of hAR binding and activation. This cell line has been reported to stably express the human androgen receptor and to be highly selective in its response to low levels of different an- drogens.

This report presents the overall statistical evaluation of the AR-CALUX® validation study organised by EURL ECVAM and serves as a supplementary source of information that cannot be captured by study reports provided by participating laboratories during the validation trial. The main focus is namely on the evaluation of the reproducibility.

Note that the classification rule was introduced during the validation trial and was ex- pected to be revised based on the data generated. This report evaluates only the classification rule as stated in the SOP. The follow-up discussions within the VMG are summarised in the main AR-CALUX® validation report.

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2 Methods

2.1 Study designFour laboratories took part in the AR-CALUX® validation trial, i.e. RISE, Citoxlab, ENVIGO and BDS. In total 46 blinded test items were used, see Table 1. The trial was structured in three sequential Studies:

Study 1 the AR-CALUX® method was transferred to the participating laboratories. Six test items were used for the successful transfer evaluation. Two main question were asked:

— Have laboratories managed to produce three valid experiments for every testitem?

— Are responses of six known test items comparable within and across laboratories?

The evaluation of the transfer is not part of this report.

Study 2 involved all four laboratories. In total 20 coded test items were under investiga-tion (Test items ID 1-20, see Table 1). Two laboratories, RISE and ENVIGO, performeda two part study: in part 1, 10 test items were tested using version 5 (V05) of theCALUX SOP, while in part 2 an additional 10 test items were tested using SOP V06.Citoxlab and BDS tested all 20 test items using SOP V06. The classification rule wasonly available in SOP V06. The classification of the 10 test items (SOP V05) tested inpart 1 at RISE and ENIGO were assigned ex post by EURL ECVAM.

Study 3 was performed only by RISE. 27 coded test items (Test items IDs 3 and 21-46, seeTable 1) were tested using SOP V06. The main purpose of this study was to generatemore data for a reliable predictive capacity evaluation.

The within laboratory reproducibility (WLR) and the predictive capacity evaluation is based on Study 2 and Study 3 whereas the between laboratory reproducibility (BLR) is calculated using the results of Study 2 only. The predictive capacity evaluation is not part of this report and can be found in the main AR-CALUX® validation study report.

The experimental steps of both versions of the AR-CALUX® SOP used in the validation trial is the same. For both agonist and antagonist testing, the first step is the determination of the highest soluble concentration followed by concentration range finding experiment (called pre-screen). When a significant signal is observed in the pre-screen, the comprehensive experiment is performed. The objective of the validation study was to produce three accepted independent biological experiments for each test item. Therefore three pre-screen (when no significant signal was observed) or three comprehensive experiments were then used for the AR-CALUX® method performance evaluation.

2

Test Item laboratory Test Item LaboratoryID Citoxlab Envigo RISE BDS ID RISE1 CIT-2-CB ENV-2-VP SPT-2-WT BDS-2-SQ 21 SPT-3-RY2 CIT-2-XF ENV-2-XN SPT-2-NM BDS-2-GG 22 SPT-3-TH3 CIT-2-AE ENV-2-HD SPT-2-HX BDS-2-CG 23 SPT-3-YC

SPT-3-AR 24 SPT-3-SB4 CIT-2-NX ENV-2-ET SPT-2-KX BDS-2-LN 25 SPT-3-VK5 CIT-2-RD ENV-2-YA SPT-2-MZ BDS-2-CW 26 SPT-3-GZ6 CIT-2-YY ENV-2-DF SPT-2-WS BDS-2-QX 27 SPT-3-RX7 CIT-2-RK ENV-2-VZ SPT-2-YP BDS-2-MU 28 SPT-3-DC8 CIT-2-XK ENV-2-QF SPT-2-NS BDS-2-WW 29 SPT-3-VE9 CIT-2-LK ENV-2-ZR SPT-2-SH BDS-2-YN 30 SPT-3-FK10 CIT-2-GQ ENV-2-GK SPT-2-LR BDS-2-SD 31 SPT-3-JA11 CIT-2-ZT ENV-3-AT SPT-3-AM BDS-2-XH 32 SPT-3-TM12 CIT-2-DQ ENV-3-FJ SPT-3-SJ BDS-2-BU 33 SPT-3-BR13 CIT-2-TJ ENV-3-UJ SPT-3-NY BDS-2-VF 34 SPT-3-XY14 CIT-2-NN ENV-3-GU SPT-3-RU BDS-2-AJ 35 SPT-3-QM15 CIT-2-JB ENV-3-BH SPT-3-ZZ BDS-2-AN 36 SPT-3-JQ16 CIT-2-YW ENV-3-DX SPT-3-FA BDS-2-BG 37 SPT-3-NQ17 CIT-2-ML ENV-3-PU SPT-3-BL BDS-2-UE 38 SPT-3-RV18 CIT-2-PY ENV-3-KU SPT-3-QT BDS-2-CM 39 SPT-3-UA19 CIT-2-HZ ENV-3-CK SPT-3-WZ BDS-2-NZ 40 SPT-3-WJ20 CIT-2-TF ENV-3-EH SPT-3-ZV BDS-2-MK 41 SPT-3-MG

42 SPT-3-FX43 SPT-3-XR44 SPT-3-DS45 SPT-3-VR46 SPT-3-LU

Table 1: Test item codes as assigned by EURL ECVAM.

2.2 Data managementUser friendly data processing templates were developed and provided to all four partici-pating laboratories. The results for each experiment (pre-screen and/or comprehensive)were recorded into the templates together with all necessary information describing allexperimental setting.User friendly templates were developed and provided to all four participating laborato-

ries. The results for each experiment(pre-screen or comprehensive) were recorded into thetemplates together with all necessary information describing the all experimental setting.The list of all templates used in this report can be found in Appendix A.1 and A.2.

3

2.3 Acceptance criteriaThe acceptance of every experiment is based on the evaluation of acceptance criteria andexpert judgment of the study director and study personnel.

2.3.1 Agonist testing

The acceptance criteria are:

1. Reference item DHT

(a) the response shall have a sigmoidal shape;

(b) the EC50 estimate shall fall within the limits 1×10−10 - 1×10−9 M;

(c) the |CV| of the estimated log(EC50) shall be less than 1.5%;

2. Relative induction of positive control (17α-Methyltestosterone) shall be greater than30%;

3. Relative induction of negative control (Corticosterone) shall be less than 10%;

4. The Induction factor for every plate shall be greater than 20;

5. Z factor for DHT shall be greater than 0.5 for every plate.

Test item data are valid when

— The acceptance criteria for validity of the experiment and plate, as described aboveare fulfilled.

— The dose response curve is composed of minimum six concentrations from three repli-cate wells after excluding samples on basis of insolubility, cytotoxicity, operator errorsor other information.

It is further required by SOP V06 to monitor the relative induction of the test item at thelowest tested concentration. If its value is above 10%, the cause shall be identified and itsimpact on data interpretation evaluated.

2.3.2 Antagonist testing

The acceptance criteria are:

1. Reference item Flutamide

(a) the response shall have a sigmoidal shape;

(b) the IC50 estimate shall fall within the limits 1×10−7 - 1×10−6 M;

(c) the |CV| of the estimated log(IC50) shall be less than 3%;

2. Relative induction of positive control (Linuron) shall be less than 60%;

3. Relative induction of negative control (Levonorgestrel) shall be greater than 85%;

4. The Inhibition factor for every plate shall be greater than 10;

5. Z factor for Flutamide shall be greater than 0.5 for every plate.

Test item data are then valid when

— The acceptance criteria for validity of the experiment and plate, as described aboveare fulfilled.

4

— The dose response curve is composed of minimum six concentrations from three repli-cate wells after excluding samples on basis of insolubility, cytotoxicity, operator errorsor other information.

It is further required by SOP V06 to monitor the relative induction of the test item at thelowest tested concentration. If its value is above 120% or below 80%, the cause (e.g.higher SC response) shall be identified together with its impact on the data interpretationevaluated.

2.4 Statistical data analysisThe main statistic for the performance evaluation of the AR-CALUX® method is the assigned classification in three accepted experiments for both agonist and antagonist part of the method. When the responses were generated under the SOP V05 the classification was assigned ex-post by the EURL ECVAM statistician, these are test items with ID 1 to 10 for laboratory ENVIGO and RISE. For other cases, the classification was determined by the relevant laboratory.

Besides the assigned classification, the other statistics are reported here too. For agonist testing,

PC10: when the response Yc exceeds 10% then PC10 is the concentration at which theinterpolated Yc response is equal to 10%.

EC50: when the response Yc exceeds 10% and Hill curve can be fit to the response thenEC50 represents the estimated half maximal effective concentration.

For antagonist testing,

PC80: when the response Yc falls below 80% then PC80 is the concentration at which theinterpolated Yc response is equal to 80%.

IC50: when the response Yc falls 80% and Hill curve can be fit to the response then IC50

represents estimated half maximal inhibitory concentration.

The classification rule as defined in SOP V06 is stated in the following two subsections.

2.4.1 Classification for agonist properties

The response to each Test item is measured in Relative Light Units (RLU) at 8 differentconcentrations (c1, . . . , c8) in triplicate. The raw response data for test and reference itemsare first transformed into the (averaged) Relative Induction as follows:

Yc = 100× YR,c − SR

DHTR,c8 − SR, c = c1, . . . , c8 (1)

where YR,c is the response of Test item in RLU units averaged over triplicate at concentration c, DHTR,c8 is the response of DHT in RLU units averaged over replicates at concentration c8 and SR is solvent control averaged over replicates in RLU units.

For each run, a test item is considered

A. Positive when the relative induction (Yc) of the test item is equal or exceeds 10% fortwo or more consecutive concentrations.

5

B. Negative when the relative induction (Yc) of the test item does not exceed 10% for anyconcentration.

C. Inconclusive in all other cases.

2.4.2 Classification for antagonist properties

Similarly as in Section 2.4.1, the raw response data is measured in Relative Light Units(RLU) at 8 different concentrations (c1, . . . , c8) in triplicate. The raw response data for testand reference items are first transformed into the (averaged) Relative Induction as follows:

Yc = 100×YR,c − FR,c8

SR − FR,c8

, c = c1, . . . , c8 (2)

where YR,c is the response of Test item in RLU units averaged over triplicate at concentrationc, FR,c8 is the response of Flutamide in RLU units averaged over replicates at concentrationc8 and SR is solvent control averaged over replicates in RLU units.The formula (2) is applied in the same way to Specificity controls of Test item re-

sponses, in this case, the notation will be Sc.

For each run, a test item is considered

A. Positive when the following two conditions are met:

— the relative induction (Yc) of the test item is less or equal to 80% for two or moreconsecutive concentrations and

— the square of the sample correlation coefficient (R2) between relative inductionof the test item’s specificity control (Sc) and the relative induction (Yc) is less orequal to 0.9.

B. Negative when Either

— when the relative induction (Yc) of the test item is greater than 80% at all con-centrations; or

— when the relative induction (Yc) of the test item is less or equal to 80% for at least2 consecutive concentrations and the R2 is greater than 0.9.

C. Inconclusive in all other cases.

2.4.3 Reproducibility

The WLR was evaluated on the data generated in Study 2 and 3, i.e. for Citoxlab, EN-VIGO and BDS, the concordance of 20 test item’s classifications is examined, whereas WLRfor RISE laboratory is based on the extended set by 26 additional test items, i.e. 46 in total.

Three classifications are concordant when either three positive or three negative classifications are obtained. The percentage of Test items with concordant classifications is used as a measure of WLR.Note that the classification rule specified in Section 2.4.1 and 2.4.2 can lead also to

Inconclusive classification. In this case, the "worst case scenario" is applied, i.e. whenInconclusive classification occurs among three classifications, it is assumed to lead to dis-cordant classifications.In addition to the concordance of classifications, the visualization of underlying re-

sponses is made. This can provide to be useful namely when the classification acrossthree accepted experiments do not coincide.

6

2.4.4 Predictive capacity

Predictive capacity is evaluated with respect to to the reference classification identified by EURL ECVAM. The reference classification is based on reported classification in other in-vitro methods. Given that, the constructed measure of predictive capacity shall not be seen as a comparision wrt the true classification. The evaluation is not part of this report and can be found in the main AR-CALUX® validation report.

7

3 Results and discussion

An overview of accepted runs per laboratory together with the associated run ID, the exper-imental date, the corresponding passage number is reported in Appendix A.1 for Agonisttesting and in Appendix A.2 for Antagonist testing, see Tables 29-34 (pages 41-42) andTables 47-52 (pages 47-49) respectively.

Agonist testing Antagonist testingaccepted rejected total accepted rejected total

Citoxlab Study 2 15 2 17 15 9 24Envigo Study 2A 4 4 7 7

Study 2B 9 9 9 3 12Study 2 13 13 16 3 19

RISE Study 2A 5 1 6 7 7Study 3 16 16 17 3 20

BDS Study 2 10 10 17 17

Table 2: Number of accepted/rejected experiments

The Appendices also contain the overview of three accepted runs and their type (comprehensive or prescreen), the overview of the highest tested concentrations in three prescreen or prescreen and three comprehensive runs can be found there too.

3.1 Acceptance criteriaThe acceptance criteria defined in Section 2.3 are reported based on the data providedby laboratories, for Agonist testing see Tables 65-76 (pages 60-64) in Appendix B.1. ForAntagonist testing see Tables 77-88 (pages 70-74) in Appendix B.2.Descriptive statistics for Acceptance control variables are shown in Table 3 and Table 4,

the boxplots for all Acceptance control variables is plotted in Figure 1 and Figure 2.

8

Citoxlab Envigo Envigo RISE RISE BDS Envigo RISEStudy2 Study2A Study2B Study2 Study3 Study2 overall overall

DHT EC50 mean 3.47e-010 2.81e-010 3.12e-010 2.2e-010 2.86e-010 3.5e-010 3.23e-010 2.73e-010std - - - - - - - -min 2.44e-010 2.02e-010 1.05e-010 1.58e-010 2.11e-010 2.58e-010 1.05e-010 1.58e-010max 5.41e-010 4.2e-010 4.79e-010 2.62e-010 3.83e-010 4.8e-010 4.79e-010 3.83e-010

CV(logEC50) mean 0.41 0.53 0.6 0.37 0.29 0.42 0.58 0.31std 0.34 0.27 0.15 0.12 0.07 0.21 0.19 0.09min 0.16 0.24 0.43 0.27 0.18 0.18 0.24 0.18max 1.29 0.89 0.84 0.57 0.48 0.86 0.89 0.57

IF mean 129.6 66.9 71.5 56.1 76.9 84 69.3 71.6std 37.5 19.8 13.1 19.8 16.3 14.6 16.5 19.4min 54.4 38.1 52.6 22.4 45.3 54.2 38.1 22.4max 207.2 98.1 100.5 96.5 118.4 115 100.5 118.4

ZF mean 0.86 0.8 0.77 0.86 0.84 0.86 0.79 0.85std 0.1 0.11 0.13 0.06 0.06 0.08 0.12 0.06min 0.28 0.41 0.45 0.72 0.6 0.59 0.41 0.6max 0.96 0.96 0.96 0.96 0.95 0.97 0.96 0.96

PC mean 78.2 75.1 77.7 79.6 78.7 77.1 76.9 78.9std 4 10.9 5.9 4.7 3.3 6 7.5 3.5min 72.9 66.2 69.6 74.7 74.1 67.1 66.2 74.1max 85.1 88.5 88.2 85.1 84.9 83.8 88.5 85.1

NC mean 6.2 0.1 1.3 0.1 0.1 0.2 0.9 0.1std 12.1 0.7 3.1 1.1 0.6 0.2 2.5 0.7min 0.1 -0.8 0 -1.6 -0.8 -0.1 -0.8 -1.6max 40.2 1 8.9 1.5 2 0.6 8.9 2

logEC50 mean -9.46 -9.55 -9.51 -9.66 -9.54 -9.46 -9.52 -9.57std 0.1 0.14 0.21 0.09 0.07 0.09 0.21 0.07min -9.61 -9.69 -9.98 -9.8 -9.68 -9.59 -9.98 -9.8max -9.27 -9.38 -9.32 -9.58 -9.42 -9.32 -9.32 -9.42

Table 3: Agonist testing. Acceptance criteria statistics across all runs.

9

Citoxlab Envigo Envigo RISE RISE BDS Envigo RISEStudy2 Study2A Study2B Study2 Study3 Study2 overall overall

FLU IC50 mean 4.92e-007 5.06e-007 6.37e-007 5.09e-007 4.36e-007 4.85e-007 6.01e-007 4.56e-007std - - - - - - - -min 3.08e-007 2.68e-007 4.39e-007 4.2e-007 2.54e-007 3.62e-007 2.68e-007 2.54e-007max 9.86e-007 8.29e-007 8.23e-007 5.9e-007 5.74e-007 6.3e-007 8.29e-007 5.9e-007

CV(logIC50) mean 0.61 1.16 0.91 0.56 0.72 0.57 1.02 0.68std 0.34 0.66 0.44 0.1 0.46 0.14 0.55 0.42min 0.11 0.62 0.55 0.45 0.34 0.32 0.55 0.34max 1.88 2.52 1.97 0.73 2.32 0.88 2.52 2.32

IF mean 51.5 27.7 34.7 32.8 33.9 29.6 31.2 33.7std 15.2 6.1 8.9 3.9 6.1 4.9 8.4 5.8min 7.5 13.6 11.9 25 11.7 1 11.9 11.7max 89.5 37.3 54.7 40 46.1 38.7 54.7 46.1

ZF mean 0.8 0.67 0.73 0.82 0.78 0.81 0.7 0.78std 0.11 0.13 0.16 0.08 0.12 0.09 0.15 0.11min 0.32 0.35 0.09 0.55 0.25 0.57 0.09 0.25max 0.98 0.9 0.96 0.94 0.95 0.95 0.96 0.95

PC mean 11.9 9.1 16.2 13 13.5 12.4 13.1 13.4std 3.8 3.1 6.6 1.9 3.6 1.4 6.3 3.3min 0.2 3.6 8.4 10.5 8.6 9 3.6 8.6max 20.3 11.8 27.8 15.8 23.8 14.3 27.8 23.8

NC mean 177.3 112.7 132 130.8 147.4 139 123.6 144std 112.2 15.1 20.6 9.9 21.8 13.5 20.4 21min 112.7 89.6 99.1 120.3 125 119.6 89.6 120.3max 613.7 135.9 161 149.7 205 164.4 161 205

logIC50 mean -6.31 -6.3 -6.2 -6.29 -6.36 -6.31 -6.24 -6.35std 0.12 0.17 0.09 0.05 0.07 0.07 0.09 0.07min -6.51 -6.57 -6.36 -6.38 -6.6 -6.44 -6.57 -6.6max -6.01 -6.08 -6.08 -6.23 -6.24 -6.2 -6.08 -6.23

VC mean 5.7 10.9 1.6 1.2 0.1 5.5 5.7 0.3std 17.5 28.3 3.2 2.4 0.4 2.5 18.7 1.1min -10.1 -0.9 -0.2 -0.1 -0.5 -0.2 -0.9 -0.5max 73.6 75 10.2 6.5 1.3 8.5 75 6.5

Table 4: Antagonist testing. Acceptance criteria statistics across all runs.

10

Cit Env2AEnv2B Ris2 Ris3 BDS Env Ris

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Figure 1: Agonist testing. Boxplots for acceptance control variables.

11


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Figure 2: Antagonist testing. Boxplots for acceptance control variables.

3.2 Test item responsesThe following information is reported for 46 Test items tested under Agonist protocol inAppendix C, see page 75:

— Figure with single Induction replicates plotted vs concentration tested for each run and

12

laboratory,

— Figure with averaged Induction Yc for three accepted runs to evaluate within-laboratoryreproducibility for each laboratory.

— Figure with averaged Induction Yc for three accepted runs and four laboratories toevaluate between-laboratory reproducibility.1

— Table with average averaged Induction Yc for three accepted runs together with stan-dard deviations of underlying three replicates, the Inductions above threshold 10%are highlighted. Cytotoxic concentrations are also reported.

— Where applicable, the PC10 and EC50 is reported too, see Tables 15-21.

— An overview of the highest tested concentrations in three prescreens or prescreen andthree comprehensive tests is reported, see Tables 41-46. Cytotoxic concentrations arealso reported.

The information reported for 46 Test items tested under Antagonist protocol in Appendix C,see page 163:

— Figure with single Induction replicates plotted vs concentration tested for each run andlaboratory,

— Figure with averaged Induction Yc and Specificity control2 Sc for three accepted runsto evaluate within-laboratory reproducibility for each laboratory.

— Figure with averaged Induction Yc (and Sc) for three accepted runs and four laborato-ries to evaluate between-laboratory reproducibility.3

— Table with average averaged Induction Yc (and Sc) for three accepted runs togetherwith standard deviations of underlying three replicates, the Inductions below threshold80% are highlighted. Cytotoxic concentrations are also reported.

— Where applicable, the PC80, IC50 and R2 is reported too, see Tables 22-??.

— An overview of the highest tested concentrations in three prescreens or prescreen andthree comprehensive tests is reported, see Tables 59-64. Cytotoxic concentrations arealso reported.

Please note that the earlier version of this report visualized responses in mg/ml units as Test item molarities were not disclosed. This version of the statistical report shows concentrations in Molar units as requested by the VMG. However, Tables provide also concentrations in mg/ml to allow comparison of reported statistics(e.g. EC50, IC50, etc.) by laboratories to those in this report.When the relative Induction Yc is ≥ 10 in agonist testing (≤ 80 antagonist testing) at the

highest noncytotoxic concentration tested, it was further requested by VMG to visualizethe interpolated response Yc at that concentration diluted by factor 2. If all concentrationsare noncytotoxic, it corresponds to c8/2 concentration. The interpolated response is alsoreported in the corresponding Table for relevant Test Item.1Only for Test items 1 to 20.2Where applicable, i.e. for comprehensive runs only.3Only for Test items 1 to 20.

13

3.3 ClassificationsThe assigned classifications for 46 coded test items are shown in Table 5 and 6. The classi-fications for Test item 1 to 10 for laboratories Envigo and RISE were assigned by applyingrules stated in Section 2.4 to the reported data. In all other cases, the classificationscorrespond to those reported in the related Study report provided by each laboratory, theclassifications rule is identical to Section 2.4.The classifications provided by laboratories were re-checked and four corrections had to

be applied, see Notes below Tables 5 and 6.

Test item Agonist testing Antagonist testingID Citoxlab Envigo RISE BDS Citoxlab Envigo RISE BDS1 P P P P P P P P P P P P N N N I I I N N N I3 N N2 P P P P P P P P P P P P N N N N N N N N N N N N3 N N N N I N N N N N N N P P P P P P P P P P P P

N N N P P P4 P P P P P P P P P P P P N N N I N N N P P N N N5 N N N N N N N N N N N N P P P P P P P P P P P P6 N N N N N N N N N N N N P P P P P P P P P P P P7 N N N N N N N N N N N N N N N N N N N N N N N N8 N N N x4 N N N N N N N N N N N I N N N N N N I3 N9 N N N N N N N N N N N N N N I N N N I N N N N N10 N N N N N N N N N N N N P P P P P P P P P P P P11 N N N N N N N N N N N N N N N N N N N N N N N N12 N N N N N N N N N N N N N N N N N N N N N N N N13 P P P P P P P P P P P P N N N N N N N N N N N N14 N N N N N N N N N N N N P P P P P P P P P P P P15 N N N N N N N N N N N N P P P P P P P FP P P P P16 P P P P P P P P P P P P N N N N N N N N N N N N17 P P P P P P P P I P P P P P P P P P P P P P P P18 N N N N N N N N N N N N P P P P P P P P I P P P19 N N N N N N N N N N N N I N I I1 N I2 I I N I3 P I3

20 N N N N I N N N N N N N P P P P P P P P P P P P

1 Note that Envigo reported as Negative but shall be Inconclusive.2 Note that Envigo reported as Negative but shall be Inconclusive.3 Note that BDS reported as Negative but shall be Inconclusive.4 Disqualified.

Table 5: Assigned classification. Test items 1 to 20 tested at 4 laboratories: Citoxlab, Envigo, RISEand BDS.

Test item RISE Test item RISEID Agonist testing Antagonist testing ID Agonist testing Antagonist testing21 P P P N N N 34 P P P I P I22 N N N P P P 35 N N N N N N23 N N N P P P 36 N N N P P P24 N N N P P P 37 N N N P P P25 P P P N N N 38 P P P N N N26 N N N P P P 39 N N N FP1 P P27 N N N N N N 40 N N N P P P28 N N N N N N 41 N N N FP FP FP29 P P P N N N 42 N N N P P P30 N N N I I I 43 N N N FP I P31 N N N P P P 44 N N N FP FP FP32 N N N N N N 45 P P P N N N33 N N N N N N 46 N N N P P P

1 Note that RISE reported as Positive but shall be False Positive (Negative).

Table 6: Assigned classification. Test items 21 to 46 from RISE laboratory.

14

The two subsections that follows discuss the cases where three identical classificationsPPP or NNN were not obtained, i.e.

for agonist testing: Test items 3, 8, 17 and 20

for antagonist testing: Test items 1, 4, 8, 9, 15, 18, 19, 30, 34, 39 and 43.

15

3.4 Classifications for Agonist testing: discussionTest item 3 Envigo data led to two Negative and one Inconclusive classifications. The

responses from the three runs are shown in Figure 3. The responses are very similaracross three runs. The assigned Inconclusive classification is due to one concentrationwhere the averaged Induction is slightly above the threshold value 10%, i.e. it equalsto 10.3%. For details see Table 91 on page 84.

It can be concluded that Test item 3 responses tested by Envigo are reproducible,however as the highest response is close to the 10% threshold, one of the three runsresulted in an Inconclusive classification.

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Rela

tive Induction [%

]TI−ENV2HD, Envigo

run 1

run 2

run 5

DHT

Figure 3: Test item 3. Relative induction responses for accepted experiments. Envigo. Legend:relative Induction Yc (solid line).

Test item 8 Envigo data led to two Negative and one Inconclusive classifications. Theresponses from the three runs are shown in Figure 4. The Figure on the left showsthe averaged responses from three runs, while the response for run 1 is shown on theright. As can be seen, the variability of Test item 8 triplicates, at three concentrations,is quite high, leading to rejection of the run which should be repeated. For details seeTable 96 on page 99.

It can be concluded that the Test item 8 responses are reproducible at laboratoryEnvigo for two runs, i.e. run 2 and 4. The third run, i.e. run 1, shall be invalidated.

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tive Induction [%

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run 1

run 2

run 4

DHT

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16

Test item 17 RISE data led to two Positive and one Inconclusive classifications. The re-sponses from the three runs are shown in Figure 5. The responses are very similaracross three runs. The positive classifications are due to two consecutive concen-trations with response above threshold 10%. The response in run 1 is classified asInconclusive as there is only one concentration with response above the threshold, i.e.the second highest tested concentration. The highest tested concentration is reportedas cytotoxic. For details see Table 105 on page 126.

It can be concluded that the Test item 17 responses are reproducible at laboratoryRISE in all tree runs. Due to cytotoxicity in highest tested concentration in run 1, theclassification is Inconclusive.

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tive Induction [%

]TI−32BL, RISE

run 15

run 19

run 22

DHT

Figure 5: Test item 17. Relative induction responses for accepted experiments. RISE. Legend:relative Induction Yc (solid line).

Test item 20 Envigo data led to two Negative and one Inconclusive classifications. Theresponses from the three runs are shown in Figure 6. The responses are very similaracross three runs, the assigned Inconclusive classification is due to one concentrationwhere is the averaged Induction slightly above the threshold value 10%, i.e. it equalsto 11.7% in run 9. For details see Table 108 on page 135.

It can be concluded that the Test item 20 responses are reproducible at laboratoryEnvigo but due to the highest response to be close to the threshold 10%, in one ofthe three runs the classification is Inconclusive.

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run 7

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DHT


17

3.5 Classifications for Antagonist testing: discussionTest item 1 .

Envigo Envigo data led to three Inconclusive classifications from comprehensive runs.The responses of Yc and Sc from the three runs are shown in Figure 7. The re-sponses are very similar across three runs, the assigned Inconclusive classifi-cations is due to one concentration where is the averaged Induction below thethreshold value 80%, i.e. it is in the range 7-17.8%. For details see Table 136 onpage 167.It can be concluded that the Test item 1 responses are reproducible at laboratoryEnvigo. Due to only one concentration where is the response below the threshold,the classifications are Inconclusive. It shall be noted that R2 is above 0.9, theclassifications then seems to be Negative (False Positive).

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TI−ENV2VP, Envigo

run 5

run 6

run 7

Flutamide

Figure 7: Test item 1. Relative induction responses for accepted experiments. Envigo. Legend:relative Induction Yc (solid line), Specificity control Sc (dashed line).

BDS BDS data led to two Negative and one Inconclusive classifications from three pre-screen runs. The responses of Yc from the three runs are shown in Figure 8. Theresponses are similar across three runs, the assigned Inconclusive classificationis due to one concentration where is the averaged Induction below the thresholdvalue 80%, i.e. it is 28.7% in run 1. The same concentration is reported to becytotoxic in remaining two runs, i.e. run 3 and 4. For details see Table 136 onpage 167. It can be concluded that the Test item 1 responses are reproducible atlaboratory BDS. The (same) highest tested concentration is reported in two out ofthree runs cytotoxic. If the concentration is treated as cytotoxic in all three runs,three Negative classifications are obtained.

Test item 4 .

Envigo Envigo data led to to two Negative and one Inconclusive classifications fromthree prescreen runs. The responses of Yc from the three runs are shown inFigure 9. The responses are similar across three runs, the assigned Inconclusiveclassification is due to one concentration, the 3rd highest tested concentration,where is the averaged Induction below the threshold value 80%, i.e. 77.5%. Fordetails see Table 141 on page 183.It can be concluded that the Test item 4 responses are reproducible at laboratoryEnvigo. Response from run 1 was classified as Inconclusive, however given the

18

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run 1

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Flutamide

Figure 8: Test item 1. Relative induction responses for accepted experiments. BDS. Legend: relativeInduction Yc (solid line).

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run 1

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Flutamide


19

variability across concentrations tested and the pattern observed, the classifica-tion shall be changed from Inconclusive to Negative.

RISE RISE data led to two Positive and one Negative classifications based on threecomprehensive runs. The responses of Yc and Sc from the three runs are shownin Figure 10. The responses are similar across three runs. The two positiveclassifications are obtained in run 8 and run 11. Run 8 has 4 highest testedconcentrations with averaged Induction below 80%, i.e. values are within range70.2-77.3%. The response starts at 81.5% and is followed by a slight decrease.

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tive Induction [%

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TI−01KX, RISE

run 6

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run 11

Flutamide

Figure 10: Test item 4. Relative induction responses for accepted experiments. RISE. Legend:relative Induction Yc (solid line), Specificity control Sc (dashed line).

Run 11 has 2 consecutive concentrations with averaged Induction below 80%, i.e. with values 79.2 and 79.8%. The R2 values for these runs are 0.03 and 0.33, i.e. below 0.9. The responses in run 8 and 11 do not show decrease of the signal as concentration increases. These data shall be used for the revision of the classification rule as the responses itself shall led to Negative classification instead.The negative classification comes from run 6. For details see Table 141 on page 183.

Test item 8 Both Envigo and BDS data led to two Negative and one Inconclusive classifi-cations. The responses from the three runs are shown in Figure 11. The responses arevery similar across the three runs, the assigned Inconclusive classification is due toone concentration where the averaged Induction is slightly below the threshold value80%, i.e. 77.2% for Envigo in run 1 and 76.7% for BDS in run 3. For details see Table148 on page 204.

It can be concluded that the Test item 8 responses are reproducible at the laboratoryEnvigo and BDS but due to the lowest response to be close to the threshold 80%, inone of the three runs the classification is Inconclusive.

Test item 9 Both Citoxlab and RISE data led to two Negative and one Inconclusive clas-sifications. Citoxlab classifications are based on three pre-screen runs where as RISEclassifications are based on three comprehensive runs. The responses from the threeruns are shown in Figure 12. The responses are very similar across three runs, theassigned Inconclusive classification is due to one concentration where the averagedInduction is slightly below the threshold value 80%, i.e. 77.9% for Citoxlab in run 15and 77.6% for RISE in run 3. For details see Table 149 on page 209.

20

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Flutamide

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tive Induction [%

]

TI−BDS2WW, BDS

run 2

run 3

run 4

Flutamide

Figure 11: Test item 8. Relative induction responses for accepted experiments. Envigo and BDS.Legend: relative Induction Yc (solid line).

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TI−CIT2LK, Citoxlab

run 5

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Flutamide

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TI−02SH, RISE

run 3

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Flutamide

Figure 12: Test item 9. Relative induction responses for accepted experiments. Citoxlab and RISE.Legend: relative Induction Yc (solid line), Specificity control Sc (dashed line).

21

It can be concluded that the Test item 9 responses are reproducible within the labo-ratory Citoxlab and RISE but due to the lowest response to be close to the threshold80% at highest tested concentration, in one of the three runs the classification isInconclusive.

The responses by RISE might be further considered all Negative.

Test item 15 RISE data led to two Positive and one Negative classifications based on threecomprehensive runs. The responses of Yc and Sc from the three runs are shown inFigure 13. The responses Yc are almost identical across three runs. The two positiveclassifications are obtained in run 12 and run 30 with R2 equal to 0.62 and 0.8, thenegative (false positive) in run 24 with R2 = 0.91.

For details see Table 158 on page 239.

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TI−28ZZ, RISE

run 13

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run 31

Flutamide


Test item 18 RISE data led to two Positive and one Inconclusive classifications based oncomprehensive runs. The responses of Yc and Sc from the three runs are shown inFigure 14. The responses are very similar across three runs. As can be seen from the

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TI−30QT, RISE

run 13

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run 25

Flutamide


figure below, the response of the second highest concentration is close to the threshold80%. Where as in two runs (12 and 15) the Induction is 78.2 and 78.6 in run 24 is83%. For details see Table 163 on page 255.

22

It can be concluded that the Test item 18 responses are reproducible at laboratoryRISE. It shall be noted that R2 is well below 0.9 in all three runs.

Test item 19 Citoxlab, Envigo and RISE data led to two Inconclusive and one Negativeclassification. BDS data led to two Inconclusive and one Positive classification. All lab-oratories but Envigo based the classifications on comprehensive runs. The responsesof Yc and Sc from the three runs are shown in Figure 15. The responses are very

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TI−CIT2HZ, Citoxlab

run 9

run 16

run 20

Flutamide

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ela

tive Induction [%

]

TI−ENV3CK, Envigo

run 1

run 2

run 3

Flutamide

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TI−20WZ, RISE

run 20

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Flutamide

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TI−BDS2NZ, BDS

run 5

run 7

run 9

Flutamide

Figure 15: Test item19. Relative induction responses for accepted experiments in three participatinglabs. Aggregated by laboratory. Legend: relative Induction Yc (solid line), Specificity control Sc

(dashed line).

similar across three runs and 4 laboratories, the Induction decreases, slightly below 80%, for highest concentration tested, see Figure 16. For details see Table 149 on page 209. It can be concluded that the Test item 19 responses Yc are reproducible within and across all 4 laboratories. Due to the lowest response close to the threshold 80% for highest tested concentration, the classification is Inconclusive for one of the three runs in 3 laboratories. At BDS two concentrations have Induction below 80% in one of the three runs with R2 = 0.43, classification is therefore Positive.

Test item 30 RISE data led to to two Inconclusive classifications from three comprehen-sive runs. The responses of Yc and Sc from the three runs are shown in Figure 17. Theresponses are similar across three runs. In all three runs there is one concentration,the highest tested concentration, where the Induction is below the threshold 80%. Itseems that the specificity control Sc has the same pattern across concentrations testedas Induction Yc, the R2 are all above 0.9. For details see Table 182 on page 284.

23

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tive Induction [%

]

Test item 19, all labs

Citoxlab

Envigo

RISE

BDS

Flutamide

Figure 16: Test item 19. Relative induction responses for accepted experiments in three participart-ing labs. Aggregated by laboratory and biological replicate. Legend: relative Induction Yc (solid line),Specificity control Sc (dashed line).

It can be concluded that the Test item 30 responses are reproducible at laboratoryRISE. The Assigned classification is Inconclusive but it seems that Test item 30 isNegative, i.e. False positive.

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TI−07FK, RISE

run 20

run 27

run 30

Flutamide


Test item 34 RISE data led to two Inconclusive and one Positive classification from three comprehensive runs. The responses of Yc and Sc from the three runs are shown in Figure 18. The responses are similar across three runs. In all three runs Inductionis below 80%, for the highest tested concentration, the second highest concentration response is distributed around 80% and in 1 out of 3 runs is below. The specificity control Sc seems to decrease earlier then Induction Yc. The R2 values are below 0.9.

24

For details see Table 188 on page 290.

These data shall be used for the revision of the classification rule as the responses itself shall led to Negative (False Positive) classification instead.

It can be concluded that the Test item 34 responses are reproducible at laboratoryRISE. The classification rule does not take into account earlier decrease of the Sc thanYc, shall not be applicable therefore.

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]

TI−36XY, RISE

run 16

run 20

run 31

Flutamide


Test item 39 RISE data led to two Positive and one False Positive classification from threecomprehensive runs. The responses of Yc and Sc from the three runs are shown inFigure 19. The responses are similar across three runs. The Induction Yc is in all threeruns below 80% for 5-6 highest consecutive concentrations. The specificity control Sc

seems to be decreasing very slowly and does not show a clear change point. In tworuns are the R2 values are below 0.9, i.e. 0.34 and 0.81, whereas in one run is equalto 0.95. For details see Table 196 on page 298.

These data shall be used for the revision of the classification rule as the pattern of responses itself shall led to Positive classification in all three runs. The classification rule does not perform well when the specificity control Induction does not have a clear change point downwards.

It can be concluded that the Test item 39 responses are reproducible at laboratoryRISE. The classification rule does not perform well here, shall not be applicable there-fore.

Test item 43 RISE data led to one Positive, one False Positive and one Inconclusive classi-fications, all based on three comprehensive runs. The responses of Yc and Sc from thethree runs are shown in Figure 20. The responses are similar across three runs. Inall three runs the highest tested concentration has Induction Yc below 80%, the sec-ond highest concentration response is distributed around 80%, i.e. values are 75.1%,75.6% in run 2 and 34, whereas in run 7 is 111.5% which seems to be an outlier(based on comparison to responses from other two runs). The R2 is 0.97 for run 2,0.89 for run 34 and 0.76 for run 7. For details see Table 204 on page 306.

It can be concluded that the Test item 43 responses are reproducible at laboratoryRISE. The differences in classifications comes from (1) possible outlier in run 7 and(2) from likely the borderline value for R2.

25

−8 −7 −6 −50

20

40

60

80

100

120

140

160

180

200

220

240

260

280

300

320

340

log10(M)

Rela

tive Induction [%

]

TI−16UA, RISE

run 20

run 27

run 34

Flutamide


−9 −8 −7 −6 −50

20

40

60

80

100

120

140

160

180

200

220

240

260

log10(M)

Rela

tive Induction [%

]

TI−26XR, RISE

run 2

run 4

run 8

Flutamide


26

3.6 ReproducibilityThe measures of reproducibility are reported here, i.e. the within-laboratory reproducibility(WLR) and between-laboratory reproducibility (BLR). The classifications reported in TableTable 5 and 6 are used.

WLR

The WLR is evaluated as stated in Section 2.4.3 and reported in Table 7. In order toevaluate WLR based on concordant classifications, a conservative approach was used herefor Inconclusive (I) outcomes, i.e. when I classifications is present in the triplicate, it isconsidered to lead to discordant triplicate ("the worst case scenario"). The WLR valuesrange from 89% to 100% for agonist and from 75% to 90% for antagonist testing.The detailed discussion in Section 3.4 revealed that most of the cases where Inconclusive

or different classifications (P or N) were obtained is linked to the classification rule but notto the reproducibility of underlying Relative Induction responses Yc.

Agonist testing Antagonist testingCitoxlab Envigo RISE BDS Citoxlab Envigo RISE BDS

Number of Test items 20 191 20(20+26) 20 20 20 20(20+26) 20Number of concordant Test items 20 17 19(19+26) 20 18 16 15(15+22) 17

WLR 100% 89% 95%(97.8%) 100% 90% 80% 75%(80.4%) 85%1 Note that one run for Test item 8 was disqualified for Envigo.

Table 7: WLR

BLR

The BLR is typically evaluated on single classifications coming from three laboratories only.Given that 4 laboratories were involved in the validation trial, BLR is evaluated for 4 pos-sible combinations of three laboratories (123 124 134 234). In addition, an overall BLRis calculated as an averaged of 4 underlying BLRs. The single classification per laboratorywas identified via the majority rule, i.e. first, an overall classification per lab is determinedas the one corresponding to classification present at most, i.e. twice. Then the proportionof concordant overall classifications for three labs represents the BLR, see Table 9 for ma-jority rule derived classifications. BLR values are shown in Table 8. Similarly a "worst casescenario" is applied when Inconclusive classification is present.

For agonist testing is BLR 100% in all possible (triplicate) combinations of 4 laboratories.For antagonist testing, the majority rule leads to BLR equal to 85% for [Citoxlab, Envigo,RISE] and [Envigo, RISE, BDS]. Triplicates [Citoxlab, Envigo, BDS] and [Citoxlab, RISE,BDS] have both BLR equal to 90%. An overall BLR for antagonist testing is 87.5%.

Agonist testing Antagonist testing4 possible triplicates 4 possible triplicates

lab 1 Citoxlab Citoxlab Envigo Citoxlab Citoxlab Citoxlab Envigo Citoxlablab 2 Envigo Envigo RISE RISE Envigo Envigo RISE RISElab 3 RISE BDS BDS BDS RISE BDS BDS BDS2of3

Number of Test items 20 20 20 20 20 20 20 20Number of concordant Test items 20 20 20 20 17 18 17 18

BLR 100% 100% 100% 100% 85% 90% 85% 90%Overall BLR 100% 87.5%

Table 8: BLR

27

Test item Agonist testing Antagonist testingID Citoxlab Envigo RISE BDS Citoxlab Envigo RISE BDS1 P P P P N N N2 P P P P N N N N3 N N N N P P P P

N P4 P P P P N N P N5 N N N N P P P P6 N N N N P P P P7 N N N N N N N N8 N N N N N N N N9 N N N N N N N N10 N N N N P P P P11 N N N N N N N N12 N N N N N N N N13 P P P P N N N N14 N N N N P P P P15 N N N N P P P P16 P P P P N N N N17 P P P P P P P P18 N N N N P P P P19 N N N N20 N N N N P P P P

Table 9: Assigned classification per lab based on the majority rule. i.e. 2 out of 3 rule.

Test item RISE Test item RISEID Agonist Antagonist ID Agonist AntagonistID testing testing ID testing testing21 P N 34 P22 N P 35 N N23 N P 36 N P24 N P 37 N P25 P N 38 P N26 N P 39 N P27 N N 40 N P28 N N 41 N N29 P N 42 N P30 N 43 N31 N P 44 N N32 N N 45 P N33 N N 46 N P

Table 10: Assigned classification per lab based on the majority rule. i.e. 2 out of 3 rule. RISE, Testitems 21-46.

28

3.7 Other3.7.1 Potency statistics

PC10 log(PC10)Test item ID Citoxlab Envigo RISE BDS geo mean Test item ID Citoxlab Envigo RISE BDS mean stdev cv

1 2.01E-08 1.02E-08 1.32E-08 1.34E-08 1.38E-08 1 -7.70 -7.99 -7.88 -7.87 -7.86 0.12 1.6%2 1.88E-07 9.54E-08 1.44E-07 1.37E-07 1.37E-07 2 -6.72 -7.02 -6.84 -6.86 -6.86 0.12 1.8%3 7.64E-04 7.64E-04 3 -3.12 -3.124 1.68E-06 2.26E-07 7.01E-07 8.08E-07 6.81E-07 4 -5.78 -6.64 -6.16 -6.09 -6.17 0.36 5.8%5 56 67 78 89 910 1011 1112 1213 2.61E-08 2.45E-08 2.12E-08 1.97E-08 2.27E-08 13 -7.59 -7.61 -7.68 -7.71 -7.64 0.06 0.7%14 1415 1516 1.40E-06 7.95E-07 1.09E-06 8.07E-07 9.93E-07 16 -5.86 -6.10 -5.96 -6.09 -6.00 0.12 1.9%17 3.31E-04 1.52E-04 2.24E-04 1.04E-04 1.85E-04 17 -3.48 -3.82 -3.65 -3.98 -3.73 0.21 5.7%18 1819 1920 20

Table 11: Agonist testing. Overview of averaged PC10 values.[mg/ml]

EC50 log(EC50)Test item ID Citoxlab Envigo RISE BDS geo mean Test item ID Citoxlab Envigo RISE BDS mean stdev cv

1 8.70E-08 5.93E-08 5.45E-08 6.62E-08 6.57E-08 1 -7.06 -7.23 -7.26 -7.18 -7.18 0.09 1.2%2 7.06E-07 4.95E-07 5.47E-07 5.42E-07 5.68E-07 2 -6.15 -6.31 -6.26 -6.27 -6.25 0.07 1.1%3 6.91E-06 6.91E-06 3 -5.16 -5.164 5.97E-06 9.83E-07 3.00E-06 2.99E-06 2.69E-06 4 -5.22 -6.01 -5.52 -5.53 -5.57 0.32 5.8%5 56 67 78 89 910 1011 1112 1213 1.10E-07 9.42E-08 1.06E-07 1.00E-07 1.02E-07 13 -6.96 -7.03 -6.98 -7.00 -6.99 0.03 0.4%14 1415 1516 1.22E-05 3.39E-06 5.17E-06 3.19E-06 5.11E-06 16 -4.91 -5.47 -5.28 -5.50 -5.29 0.27 5.1%17 4.03E-04 4.03E-04 17 -3.39 -3.3918 1819 1920 20

Table 12: Agonist testing. Overview of averaged EC50 values. [mg/ml]

29

PC80 log(PC80)Test item ID Citoxlab Envigo RISE BDS geo mean Test item ID Citoxlab Envigo RISE BDS geo mean stdev cv

1 2.27E-02 3.02E-02 2.62E-02 1 -1.64 -1.52 -1.58 0.09 5.5 %2 23 3.59E-06 3.39E-06 3.26E-06 6.39E-06 3.99E-06 3 -5.45 -5.47 -5.49 -5.20 -5.40 0.14 2.5 %4 45 6.14E-05 1.10E-04 7.15E-05 1.27E-04 8.85E-05 5 -4.21 -3.96 -4.15 -3.89 -4.05 0.15 3.7 %6 1.30E-05 2.33E-05 1.14E-05 4.58E-06 1.12E-05 6 -4.88 -4.63 -4.94 -5.34 -4.95 0.29 5.9 %7 78 89 910 1.99E-06 3.21E-06 2.34E-06 3.50E-06 2.69E-06 10 -5.70 -5.49 -5.63 -5.46 -5.57 0.11 2.0 %11 1112 1213 1314 5.73E-06 2.04E-05 6.65E-06 4.91E-06 7.86E-06 14 -5.24 -4.69 -5.18 -5.31 -5.10 0.28 5.5 %15 2.05E-04 2.65E-04 2.71E-04 1.69E-04 2.23E-04 15 -3.69 -3.58 -3.57 -3.77 -3.65 0.10 2.6 %16 1617 5.34E-07 1.14E-06 4.79E-07 7.15E-07 6.76E-07 17 -6.27 -5.94 -6.32 -6.14 -6.17 0.17 2.7 %18 3.87E-04 5.53E-04 4.60E-04 7.44E-04 5.20E-04 18 -3.41 -3.26 -3.34 -3.13 -3.29 0.12 3.7 %19 1920 1.09E-06 2.07E-06 1.19E-06 9.63E-07 1.27E-06 20 -5.96 -5.68 -5.92 -6.02 -5.90 0.15 2.5 %

Table 13: Antagonist testing. Overview of averaged PC80 values. [mg/ml]

IC50 log(IC50)Test item ID Citoxlab Envigo RISE BDS geo mean Test item ID Citoxlab Envigo RISE BDS geo mean stdev cv

1 1.42E-02 9.20E-03 1.14E-02 1 -1.85 -2.04 -1.95 0.13 6.9%2 23 1.52E-05 1.56E-05 1.44E-05 1.51E-05 1.51E-05 3 -4.82 -4.81 -4.84 -4.82 -4.82 0.02 0.3%4 45 3.09E-04 3.27E-04 3.00E-04 3.22E-04 3.14E-04 5 -3.51 -3.48 -3.52 -3.49 -3.50 0.02 0.5%6 5.09E-05 6.13E-05 5.30E-05 3.18E-05 4.79E-05 6 -4.29 -4.21 -4.27 -4.50 -4.32 0.12 2.9%7 78 89 910 1.17E-05 1.14E-05 1.12E-05 1.15E-05 1.14E-05 10 -4.93 -4.94 -4.95 -4.94 -4.94 0.01 0.1%11 1112 1213 1314 2.71E-05 8.78E-05 3.01E-05 1.85E-05 3.39E-05 14 -4.57 -4.06 -4.52 -4.73 -4.47 0.29 6.5%15 8.69E-04 7.48E-04 8.31E-04 8.51E-04 8.23E-04 15 -3.06 -3.13 -3.08 -3.07 -3.08 0.03 1.0%16 1617 1.50E-06 3.94E-06 2.33E-06 2.44E-06 2.41E-06 17 -5.82 -5.40 -5.63 -5.61 -5.62 0.17 3.1%18 1.78E-03 2.05E-03 5.56E-04 1.68E-03 1.36E-03 18 -2.75 -2.69 -3.26 -2.77 -2.87 0.26 9.1%19 1920 6.26E-06 7.45E-06 5.26E-06 5.16E-06 5.97E-06 20 -5.20 -5.13 -5.28 -5.29 -5.23 0.08 1.5%

Table 14: Antagonist testing. Overview of averaged IC50 values. [mg/ml]

30

Test item ID Citoxlab Envigo RISE BDS1 9.7e-008 9.6e-008 7.1e-008 6.6e-008 5.2e-008 6.1e-008 6.2e-008 5.1e-008 5.1e-008 7.1e-008 6.7e-008 6.1e-0082 8.0e-007 5.4e-007 8.2e-007 3.5e-007 5.4e-007 6.4e-007 5.8e-007 5.0e-007 5.7e-007 6.6e-007 4.8e-007 5.0e-00734 5.6e-006 5.6e-006 6.7e-006 1.9e-006 2.3e-007 2.2e-006 3.1e-006 3.7e-006 2.4e-006 3.7e-006 2.9e-006 2.5e-0065678910111213 8.9e-008 1.2e-007 1.2e-007 1.1e-007 9.3e-008 8.6e-008 1.1e-007 1.1e-007 9.5e-008 1.0e-007 1.1e-007 9.4e-008141516 1.5e-005 9.3e-006 1.3e-005 2.6e-006 3.1e-006 4.9e-006 4.4e-006 5.4e-006 5.7e-006 3.7e-006 3.4e-006 2.6e-00617 na na na na 4.0e-004 na na na na na na na181920

Table 15: Agonist testing. Overview of EC50.

Test item ID Citoxlab Envigo RISE BDS1 2.4e-008 1.9e-008 1.7e-008 1.0e-008 6.4e-009 1.6e-008 1.6e-008 1.2e-008 1.2e-008 1.4e-008 1.4e-008 1.2e-0082 1.8e-007 1.9e-007 2.0e-007 7.5e-008 9.7e-008 1.2e-007 1.6e-007 1.2e-007 1.5e-007 1.7e-007 1.2e-007 1.2e-0073 7.6e-0044 1.5e-006 1.8e-006 3.4e-007 4.7e-008 7.2e-007 8.8e-007 6.8e-007 5.8e-007 9.0e-007 8.8e-007 6.7e-0075678 na910111213 2.1e-008 2.8e-008 3.0e-008 2.9e-008 2.3e-008 2.2e-008 2.0e-008 2.4e-008 2.0e-008 2.1e-008 2.2e-008 1.7e-008141516 1.8e-006 9.5e-007 1.6e-006 7.1e-007 7.3e-007 9.7e-007 1.1e-006 1.1e-006 1.1e-006 1.0e-006 8.0e-007 6.4e-00717 2.9e-004 3.8e-004 3.3e-004 1.1e-004 1.5e-004 2.2e-004 1.7e-004 2.7e-004 2.5e-004 5.3e-005 1.7e-004 1.3e-004181920 3.2e-002

Table 16: Agonist testing. Overview of PC10.

31

Test item ID PC10 EC5021 1.2e-007 1.7e-007 1.4e-007 3.9e-007 7.7e-007 4.2e-00722232425 2.5e-008 2.3e-008 2.4e-008 1.2e-007 1.3e-007 1.3e-00726272829 2.7e-008 2.7e-008 2.7e-008 1.2e-007 1.1e-007 1.2e-0073031323334 1.2e-006 1.3e-006 1.6e-006 2.6e-006 2.8e-006 3.0e-00635363738 5.6e-008 6.1e-008 8.1e-008 2.3e-007 2.8e-007 3.4e-00739404142434445 7.0e-007 8.1e-007 6.9e-007 2.3e-006 2.7e-006 2.1e-0064647

Table 17: Agonist testing. RISE. Test items 21-46. Overview of EC50 and PC10.

32

Test item ID Citoxlab Envigo RISE BDS1 -7.01 -7.02 -7.15 -7.18 -7.29 -7.21 -7.21 -7.29 -7.29 -7.15 -7.18 -7.212 -6.1 -6.27 -6.09 -6.46 -6.27 -6.19 -6.24 -6.3 -6.25 -6.18 -6.32 -6.334 -5.25 -5.25 -5.17 -5.71 -6.64 -5.67 -5.51 -5.43 -5.63 -5.44 -5.54 -5.65678910111213 -7.05 -6.91 -6.91 -6.98 -7.03 -7.07 -6.96 -6.95 -7.02 -7 -6.97 -7.03141516 -4.82 -5.03 -4.89 -5.59 -5.51 -5.31 -5.35 -5.26 -5.24 -5.43 -5.47 -5.5917 na na na na -3.39 na na na na na na na181920

Table 18: Agonist testing. Overview of log(EC50).

Test item ID Citoxlab Envigo RISE BDS1 1.19 0.33 0.35 0.67 0.79 0.53 0.3 0.35 0.46 0.39 0.24 0.72 0.38 0.31 0.43 0.65 0.77 0.5 0.39 0.27 0.5 0.59 0.37 0.4934 1.23 1.91 1.46 1.72 1.36 1.15 0.82 0.89 0.79 1.06 1.11 1.065678910111213 0.27 0.36 0.32 0.72 0.68 0.9 0.42 0.46 0.39 0.44 0.34 0.67141516 5.13 2.39 1.75 0.96 0.88 1.05 0.92 0.88 0.9 0.25 0.29 0.617 na na na na 10.25 na na na na na na na181920

Table 19: Agonist testing. Overview of CV(log(EC50)) [%] .

33

Test item ID Citoxlab Envigo RISE BDS1 -7.61 -7.71 -7.77 -8 -8.19 -7.79 -7.81 -7.93 -7.9 -7.86 -7.85 -7.912 -6.74 -6.73 -6.7 -7.13 -7.01 -6.92 -6.8 -6.91 -6.82 -6.77 -6.9 -6.923 -3.124 -5.81 -5.74 -6.46 -7.33 -6.14 -6.06 -6.17 -6.24 -6.05 -6.06 -6.175678 na910111213 -7.69 -7.55 -7.52 -7.54 -7.63 -7.65 -7.71 -7.62 -7.7 -7.68 -7.66 -7.78141516 -5.75 -6.02 -5.8 -6.15 -6.13 -6.01 -5.96 -5.96 -5.97 -5.99 -6.1 -6.1917 -3.54 -3.42 -3.48 -3.97 -3.82 -3.66 -3.78 -3.57 -3.6 -4.27 -3.77 -3.89181920 -1.5

Table 20: Agonist testing. Overview of log(PC10).

Test item ID log(PC10) log(EC50) CV(log(EC50)) [%]21 -6.92 -6.77 -6.85 -6.41 -6.11 -6.38 0.42 0.65 0.5322232425 -7.61 -7.65 -7.61 -6.93 -6.89 -6.87 0.37 0.39 0.6826272829 -7.57 -7.57 -7.56 -6.94 -6.97 -6.91 0.46 0.36 0.453031323334 -5.92 -5.87 -5.81 -5.59 -5.56 -5.53 0.36 0.75 0.4935363738 -7.25 -7.22 -7.09 -6.63 -6.55 -6.47 0.24 0.24 0.3739404142434445 -6.15 -6.09 -6.16 -5.63 -5.57 -5.67 0.98 1.04 0.84647

Table 21: Agonist testing. RISE. Test items 21-46. Overview of log(EC50), CV(log(EC50)) andlog(PC10).

34

Test item ID Citoxlab Envigo RISE BDS1 na 1.4e-002 na23 1.6e-005 1.4e-005 1.5e-005 1.3e-005 1.8e-005 1.6e-005 1.4e-005 1.4e-005 1.5e-005 na 1.6e-005 1.4e-0054 na 2.3e-0075 3.3e-004 2.7e-004 3.3e-004 3.5e-004 2.9e-004 3.5e-004 2.9e-004 3.0e-004 3.0e-004 3.4e-004 3.2e-004 3.1e-0046 6.2e-005 5.6e-005 3.8e-005 6.5e-005 5.9e-005 6.1e-005 4.1e-005 4.1e-005 8.8e-005 2.5e-005 3.4e-005 3.8e-00578910 9.6e-006 1.1e-005 1.5e-005 7.9e-006 1.1e-005 1.6e-005 1.0e-005 1.3e-005 1.0e-005 8.4e-006 1.2e-005 1.5e-00511121314 2.6e-005 2.6e-005 2.9e-005 5.1e-005 3.4e-005 3.8e-004 3.2e-005 3.1e-005 2.8e-005 2.2e-005 3.2e-005 9.0e-00615 7.4e-004 9.7e-004 9.1e-004 6.2e-004 9.0e-004 7.6e-004 7.2e-004 9.2e-004 8.6e-004 8.7e-004 7.8e-004 9.1e-0041617 2.4e-006 1.3e-006 1.1e-006 2.9e-006 3.4e-006 6.3e-006 2.5e-006 2.7e-006 1.9e-006 2.1e-006 2.4e-006 3.0e-00618 1.6e-003 1.5e-003 2.3e-003 2.3e-003 1.6e-003 2.4e-003 na 6.4e-004 4.8e-004 1.3e-003 2.0e-003 1.8e-00319 1.7e-002 1.5e-002 na na na na 6.4e-002 1.1e-001 na20 7.3e-006 5.4e-006 6.2e-006 7.2e-006 8.4e-006 6.9e-006 5.8e-006 4.9e-006 5.2e-006 4.6e-006 4.9e-006 6.1e-006

Table 22: Antagonist testing. Overview of IC50.

Test item ID Citoxlab Envigo RISE BDS1 3.6e-002 1.6e-002 2.1e-002 3.0e-00223 4.9e-006 2.6e-006 3.7e-006 4.6e-006 3.5e-006 2.4e-006 2.5e-006 2.8e-006 4.8e-006 8.2e-006 5.0e-0064 6.5e-006 8.2e-007 1.1e-0065 7.9e-005 7.3e-005 4.0e-005 1.5e-004 5.1e-005 1.7e-004 5.1e-005 1.1e-004 6.3e-005 8.3e-005 1.5e-004 1.6e-0046 1.2e-005 1.8e-005 1.0e-005 2.8e-005 2.4e-005 1.9e-005 1.3e-005 8.8e-006 1.3e-005 2.9e-006 5.7e-006 5.9e-00678 1.3e-003 1.3e-0039 2.2e-003 1.3e-00210 1.1e-006 2.9e-006 2.4e-006 2.1e-006 2.9e-006 5.3e-006 2.3e-006 2.5e-006 2.2e-006 3.6e-006 3.4e-00611121314 7.9e-006 6.7e-006 3.5e-006 3.8e-006 7.8e-006 2.9e-004 6.2e-006 8.6e-006 5.5e-006 5.1e-006 5.0e-006 4.6e-00615 2.8e-004 2.0e-004 1.6e-004 2.4e-004 3.5e-004 2.2e-004 2.7e-004 2.6e-004 2.8e-004 1.8e-004 1.9e-004 1.4e-0041617 1.0e-006 4.7e-007 3.3e-007 8.1e-007 9.6e-007 1.9e-006 5.6e-007 5.0e-007 3.9e-007 6.1e-007 2.4e-007 2.5e-00618 4.0e-004 6.4e-004 2.3e-004 2.8e-004 5.7e-004 1.0e-003 na 4.2e-004 5.1e-004 4.5e-004 1.1e-003 8.4e-00419 3.3e-002 3.2e-002 2.2e-002 3.8e-002 4.8e-002 3.9e-002 1.2e-001 2.5e-002 5.2e-00220 1.6e-006 8.9e-007 8.9e-007 2.4e-006 2.8e-006 1.3e-006 1.4e-006 8.9e-007 1.3e-006 6.8e-007 1.2e-006 1.1e-006

Table 23: Antagonist testing. Overview of PC80.

35

Test item ID PC80 IC502122 1.5e-006 7.6e-007 7.7e-007 3.3e-006 3.5e-006 3.8e-00623 4.1e-004 4.3e-004 4.2e-004 5.5e-004 6.5e-004 6.0e-00424 3.6e-005 4.0e-005 3.2e-005 2.6e-004 2.1e-004 1.8e-0042526 5.1e-005 3.6e-005 1.7e-005 2.1e-004 1.5e-004 1.7e-00427282930 3.4e-006 1.7e-006 1.9e-006 4.8e-006 1.7e-006 1.7e-00631 6.3e-005 8.6e-005 1.1e-004 3.7e-004 5.2e-004 4.0e-004323334 2.0e-003 na 3.0e-003 na na na3536 8.4e-007 5.3e-007 5.2e-007 2.9e-006 2.7e-006 2.7e-00637 1.0e-004 1.0e-004 5.7e-005 4.3e-004 5.0e-004 3.5e-0043839 3.8e-005 4.9e-005 3.1e-005 3.6e-004 2.3e-004 9.2e-00540 5.9e-005 5.3e-005 4.9e-005 1.5e-004 1.6e-004 1.6e-00441 1.3e-003 1.4e-003 5.9e-004 4.0e-003 4.2e-003 3.7e-00342 1.5e-004 1.2e-004 8.8e-005 5.7e-004 4.6e-004 5.5e-00443 3.5e-004 3.5e-004 1.1e-003 na 1.2e-003 na44 1.8e-004 8.5e-005 1.3e-004 2.7e-004 1.5e-004 1.7e-0044546 4.8e-006 5.0e-006 3.9e-006 1.6e-005 1.0e-005 1.0e-00547 5.9e-006 5.1e-006 1.8e-006 1.5e-005 1.8e-005 1.1e-005

Table 24: Antagonist testing. RISE. Test items 21-46. Overview of IC50 and PC80. [mg/ml]

Test item ID Citoxlab Envigo RISE BDS123 -4.79 -4.84 -4.82 -4.87 -4.76 -4.79 -4.84 -4.87 -4.82 na -4.8 -4.844 na na -6.655 -3.48 -3.58 -3.48 -3.46 -3.54 -3.45 -3.53 -3.52 -3.52 -3.47 -3.49 -3.516 -4.21 -4.25 -4.42 -4.19 -4.23 -4.22 -4.39 -4.38 -4.05 -4.6 -4.47 -4.4278910 -5.02 -4.97 -4.81 -5.1 -4.94 -4.79 -4.98 -4.87 -5 -5.08 -4.91 -4.8311121314 -4.58 -4.58 -4.54 -4.29 -4.46 -3.42 -4.5 -4.51 -4.56 -4.66 -4.49 -5.0515 -3.13 -3.01 -3.04 -3.21 -3.05 -3.12 -3.14 -3.04 -3.06 -3.06 -3.11 -3.041617 -5.62 -5.89 -5.96 -5.54 -5.47 -5.2 -5.61 -5.57 -5.72 -5.69 -5.62 -5.5318 -2.8 -2.82 -2.63 -2.65 -2.8 -2.62 na -3.19 -3.32 -2.88 -2.7 -2.7419 -1.78 -1.82 na na na na -1.2 -0.98 na20 -5.13 -5.27 -5.21 -5.14 -5.08 -5.16 -5.24 -5.31 -5.29 -5.34 -5.31 -5.22

Table 25: Antagonist testing. Overview of log(IC50).

36

Test item ID Citoxlab Envigo RISE BDS123 2.64 1.49 0.89 1.98 2.22 6.65 1.38 0.84 1.34 na 1.61 1.884 na na 4.055 0.93 0.87 1.2 1.81 1.4 2.23 0.82 1 0.75 0.85 0.59 1.066 1.3 0.83 0.97 1.34 1.66 3.55 0.95 1.08 3.06 0.78 0.93 0.9978910 1.81 0.95 2.66 2.06 2.3 1.7 1.29 1.26 0.92 3.76 1.16 0.9711121314 0.78 0.72 0.58 2.33 1.66 4.97 0.8 0.84 0.51 0.55 0.84 1.6715 1.44 3.93 1.97 2 1.76 3.04 3.53 2.25 1.63 1.26 1.44 1.341617 2.6 2.57 2.9 4.47 1.29 1.68 0.93 1.02 1.64 1.35 1.17 1.1218 1.31 0.95 3.59 3.82 2.07 2 na 7.35 na 0.91 1.48 0.7119 na na na na na na na20 0.59 1.34 0.56 3.24 0.96 1.04 0.87 0.37 0.62 0.55 0.66 0.51

Table 26: Antagonist testing. Overview of CV(log(IC50)) [%].

Test item ID Citoxlab Envigo RISE BDS1 -1.44 -1.81 -1.68 -1.5223 -5.31 -5.59 -5.44 -5.33 -5.45 -5.62 -5.6 -5.55 -5.32 -5.09 -5.34 -5.18 -6.09 -5.965 -4.1 -4.13 -4.4 -3.82 -4.29 -3.76 -4.29 -3.95 -4.2 -4.08 -3.82 -3.786 -4.92 -4.74 -4.99 -4.55 -4.63 -4.72 -4.89 -5.06 -4.87 -5.54 -5.24 -5.2378 -2.88 -2.99 -2.65 -1.910 -5.94 -5.53 -5.62 -5.67 -5.54 -5.27 -5.63 -5.6 -5.66 -5.44 -5.4711121314 -5.1 -5.17 -5.45 -5.42 -5.11 -3.54 -5.21 -5.06 -5.26 -5.29 -5.3 -5.3415 -3.55 -3.7 -3.81 -3.62 -3.45 -3.66 -3.57 -3.58 -3.56 -3.75 -3.71 -3.851617 -6 -6.33 -6.49 -6.09 -6.02 -5.72 -6.25 -6.3 -6.41 -6.21 -6.61 -5.6118 -3.4 -3.2 -3.64 -3.55 -3.24 -2.98 na -3.38 -3.3 -3.34 -2.97 -3.0819 -1.48 -1.49 -1.65 -1.42 -1.32 -1.41 -0.91 -1.61 -1.2820 -5.79 -6.05 -6.05 -5.62 -5.55 -5.88 -5.84 -6.05 -5.88 -6.17 -5.92 -5.96

Table 27: Antagonist testing. Overview of log(PC80).

37

Test item ID log(PC80) log(IC50) CV(log(IC50))2122 -5.81 -6.12 -6.12 -5.48 -5.45 -5.42 1.62 0.77 1.0923 -3.38 -3.36 -3.37 -3.26 -3.19 -3.22 2.12 2.43 1.924 -4.44 -4.4 -4.49 -3.58 -3.68 -3.75 1.27 1.03 1.382526 -4.29 -4.45 -4.78 -3.69 -3.81 -3.76 2.37 1.23 1.48272829 -1.61 -2.07 1404921.330 -5.47 -5.78 -5.72 -5.32 -5.78 -5.76 677424775899717.5 23536.14 10412.0531 -4.2 -4.07 -3.97 -3.43 -3.29 -3.4 2.92 4.69 3.2932 -2 -2.16 32928.923334 -2.7 na -2.53 na na na3536 -6.08 -6.28 -6.29 -5.53 -5.57 -5.57 0.68 0.9 0.8837 -3.98 -3.98 -4.24 -3.37 -3.3 -3.45 1.23 0.95 0.543839 -4.42 -4.31 -4.51 -3.44 -3.64 -4.04 1.12 1.29 4.3440 -4.23 -4.28 -4.31 -3.81 -3.8 -3.79 0.9 0.76 0.7541 -2.88 -2.85 -3.23 -2.4 -2.37 -2.43 2.05 5.98 3.0242 -3.82 -3.91 -4.06 -3.24 -3.33 -3.26 1.47 2.05 1.4443 -3.46 -3.45 -2.96 na -2.93 na 16.1744 -3.73 -4.07 -3.88 -3.57 -3.83 -3.77 3.91 818.89 1.345 -5.07 na46 -5.32 -5.3 -5.4 -4.79 -4.98 -4.99 2.09 2.45 0.5947 -5.23 -5.29 -5.75 -4.82 -4.75 -4.95 0.79 1.06 0.9

Table 28: Antagonist testing. RISE. Test items 21-46. Overview of log(IC50) and log(PC80) [mg/ml]

38

3.7.2 Variability measures

The evaluation of variability is performed at different levels:

— all test items: coefficient of variation for all triplicates where Yc > 1%, see Figure 21;

— DHT only

• coefficient of variation of all triplicates where Yc > 1%, see WRV in Figure 22;

• coefficient of variation for Yc’s across three runs(Yc > 1%), see WLV in Figure 22;

• coefficient of variation for Yc’s across three labs(Yc > 1%), see WLV in Figure 22;

— Flutamide only

• coefficient of variation of all triplicates where Yc > 1%, see WRV in Figure 23;

• coefficient of variation for Yc’s across three runs(Yc > 1%), see WLV in Figure 23;

• coefficient of variation for Yc’s across three labs(Yc > 1%), see WLV in Figure 23.

0.1 0.32 1 3.16 10 31.62 100

0.2

0.4

0.6

0.8

1

1.2

1.4

1.6

1.8

CV [%] − log scale

Agonist testing − estimated density of CVs

Citoxlab

Envigo

RISE

BDS

0.32 1 3.16 10 31.62 100

0.2

0.4

0.6

0.8

1

1.2

1.4


Antagonist testing − estimated density of CVs

Citoxlab

Envigo

RISE

BDS

Figure 21: Variability of triplicates. Coefficient of variation estimated density distribution. Only datawhere Yc > 1% are used.

0.32 1 3.16 10 31.62 1000

0.2

0.4

0.6

0.8

1

1.2


WRV − DHT only

Citoxlab

Envigo

RISE

BDS

0.1 0.32 1 3.16 10 31.62 100 316.230

0.1

0.2

0.3

0.4

0.5

0.6

0.7

0.8


WLV − DHT only

Citoxlab

Envigo

RISE

BDS

0.01 0.03 0.1 0.32 1 3.16 10 31.62 100 316.230

0.1

0.2

0.3

0.4

0.5

0.6

0.7

0.8


BLV − DHT only

CER

CEB

CRB

ERB

Figure 22: DHT data only. Within-Run-Variability (WRV), Within-Lab-Variability (WLV), Between-Lab-Variability (BLV) expressed as the estimated density distribution for coefficient of variation(CV).

39

0.32 1 3.16 10 31.62 1000

0.2

0.4

0.6

0.8

1


WRV − FLU only

Citoxlab

Envigo

RISE

BDS

0.01 0.03 0.1 0.32 1 3.16 10 31.62 100 316.230

0.2

0.4

0.6

0.8

1


WLV − FLU only

Citoxlab

Envigo

RISE

BDS

0.03 0.1 0.32 1 3.16 10 31.62 100 316.230

0.2

0.4

0.6

0.8

1


BLV − FLU only

CER

CEB

CRB

ERB

Figure 23: ]Flutamide data only. Within-Run-Variability (WRV), Within-Lab-Variability (WLV),Between-Lab-Variability (BLV) expressed as the estimated density distribution for

coefficient of variation(CV).

40

Appendix A Overview of accepted runs

A.1 Agonist testing

run ID Date passage file namerun 1 04/07/2018 9 Citoxlab-45631 RD-AG02-PRE-20180703-first serie.xlsmrun 2 04/07/2018 9 Citoxlab-45631 RD-AG02-PRE-20180703-second serie.xlsmrun 3 05/09/2018 11 DAT02-ASY06-v05-AG05 20180904 first serie.xlsmrun 4 05/09/2018 11 DAT02-ASY06-v05-AG05 20180904 second serie.xlsmrun 5 06/09/2018 11 DAT02-ASY06-v05-AG06-20180905-first serie-comprehensive test.xlsmrun 6 06/09/2018 11 DAT02-ASY06-v05-AG06-20180905-first serie-prescreen test.xlsmrun 7 06/09/2018 11 DAT02-ASY06-v05-AG06-20180905-second serie-prescreen test.xlsmrun 8 19/09/2018 15 DAT02-ASY06-v05-45631 RD-AG09-first serie-COMP.xlsmrun 9 19/09/2018 15 DAT02-ASY06-v05-45631 RD-AG09-second serie comprehensive test.xlsmrun 10 19/09/2018 15 DAT02-ASY06-v05-45631 RD-AG09-second serie prescreen test.xlsmrun 11 20/09/2018 15 DAT02-ASY06-v05-45631 RD-AG10-first serie.xlsmrun 12 20/09/2018 15 DAT02-ASY06-v05-45631 RD-AG10-second serie.xlsmrun 13 03/10/2018 19 DAT02-ASY06-v05-AG13-first serie-comp.xlsmrun 14 03/10/2018 19 DAT02-ASY06-v05-AG13-first serie-pre.xlsmrun 15 03/10/2018 19 DAT02-ASY06-v05-AG13-second serie-pre.xlsmrun 16 18/10/2018 23 Citoxlab-DAT02-ASY06-v06-45631 RD-20181016-AG19-Dilution factor 5.xlsmrun 17 25/10/2018 25 Citoxlab-DAT02-ASY06-v06-45631 RD-20181024-AG22-Dilution factor 5-COMP.xlsmrun 18 25/10/2018 25 Citoxlab-DAT02-ASY06-v06-45631 RD-20181024-AG22-PRE.xlsmrun 19 31/10/2018 27 Citoxlab-DAT02-ASY06-v06-45631 RD-20181030-AG24-Dilution factor 5-COMP.xlsm

Table 29: Citoxlab. Study2. Overview of accepted runs.

run ID Date passage file namerun 1 19/01/2017 9 ENV-pAG01-received 2017 02 09 mail.xlsmrun 2 25/01/2017 11 ENV-pAG02-received 2017 03 21.xlsmrun 3 25/01/2017 11 ENV-cAG01-received 2017 03 21.xlsmrun 4 09/02/2017 15 ENV-pAG03-received 2017 03 21.xlsmrun 5 09/02/2017 15 ENV-cAG02-received 2017 03 21.xlsmrun 6 15/02/2017 17 ENV-pAG04-received 2017 03 21.xlsmrun 7 15/02/2017 17 ENV-cAG03-received 2017 03 21.xlsm

Table 30: Envigo. Study2A. Overview of accepted runs.

run ID Date passage file namerun 1 07/06/2017 13 ENV2B-pAG01-AG.xlsmrun 2 14/06/2017 15 ENV2B-pAG01-ENV-3-CK-AT-DX-UJ.xlsmrun 3 28/06/2017 19 ENV2B-cAG02.xlsmrun 4 19/07/2017 25 ENV2B-pAG04.xlsmrun 5 26/07/2017 27 ENV2B-cAG03.xlsmrun 6 02/08/2017 29 ENV2B-cAG04.xlsmrun 7 18/10/2017 20 ENV2B-pAG05.xlsmrun 8 18/10/2017 20 ENV2B-cAG05.xlsmrun 9 08/11/2017 26 ENV2B-pAG06.xlsmrun 10 06/12/2017 7 ENV2B-pAG07.xlsm

Table 31: Envigo. Study2B. Overview of accepted runs.

run ID Date passage file namerun 1 02/11/2016 7 SPT-161031-1ep-2ep-3ep-4ep-5ep-6ep-AGPRE.xlsmrun 2 09/11/2016 9 SPT-161107-1jj-2jj-3jj-4jj-AGPRE.xlsmrun 3 09/11/2016 9 SPT-161107-1jj-5jj-6jj-AGCOM.xlsmrun 4 30/11/2016 15 SPT-161128-1ep-5ep-AGPRE.xlsmrun 5 30/11/2016 15 SPT-161128-1ep-2ep-3ep-4ep-AGCOM.xlsmrun 6 07/12/2016 17 SPT-161205-1kf-4kf-6kf-AGPRE.xlsmrun 7 07/12/2016 17 SPT-161205-1kf-2kf-3kf-5kf-6kf-AGCOM.xlsmrun 8 14/12/2016 19 SPT-161212-1ep-2ep-3ep-AGCOM.xlsm

Table 32: RISE. Study2. Overview of accepted runs.

41

run ID Date passage file namerun 1 24/05/2017 3 SPT-170524-1ep-2ep-3ep-4ep-5ep-6ep-AGPRE.xlsmrun 2 21/06/2017 11 SPT-170619-1ep-2ep-3ep-4ep-AGPRE.xlsmrun 3 28/06/2017 13 SPT-170626-1ep-2ep-3ep-4ep-5ep-AGPRE.xlsmrun 4 12/07/2017 17 SPT-170710-1lb-2lb-AGCOM.xlsmrun 5 12/07/2017 17 SPT-170710-1lb-3lb-4lb-AGPRE.xlsmrun 6 13/09/2017 3 SPT-170911-1lb-2lb–3lb-AGPRE.xlsmrun 7 13/09/2017 3 SPT-170911-1lb-4lb-AGCOM.xlsmrun 8 20/09/2017 5 SPT-170918-1jj-2jj-3jj-4jj-AGPRE.xlsmrun 9 20/09/2017 5 SPT-170918-1jj-5jj-6jj-AGCOM.xlsmrun 10 04/10/2017 9 SPT-171002-1lb-2lb-3lb-4lb-AGPRE.xlsmrun 11 04/10/2017 9 SPT-171002-1lb-5lb-6lb-AGCOM.xlsmrun 12 18/10/2017 13 SPT-171016-1ep-2ep-3ep-AGPRE.xlsmrun 13 08/11/2017 19 SPT-171106-1ta-2ta-AGCOM.xlsmrun 14 08/11/2017 19 SPT-171106-1ta-3ta-4ta-5ta-6ta-AGPRE.xlsmrun 15 22/11/2017 23 SPT-171120-18jj-2jj-3jj-4jj-AGCOM.xlsmrun 16 22/11/2017 23 SPT-171120-18jj-4jj-5jj-6jj-AGPRE.xlsmrun 17 29/11/2017 25 SPT-171127-1ta-2ta-AGCOM.xlsmrun 18 29/11/2017 25 SPT-171127-1ta-3ta-4ta-5ta-6ta-AGPRE.xlsmrun 19 24/01/2018 3 SPT-180122-1ep-2ep-3ep-4ep-5ep-AGCOM.xlsmrun 20 24/01/2018 3 SPT-180122-1ep-6ep-AGPRE.xlsmrun 21 31/01/2018 5 SPT-180129-1lb-2lb-3lb-4lb-5lb-AGPRE.xlsmrun 22 31/01/2018 5 SPT-180129-1lb-5lb-6lb-AGCOM.xlsmrun 23 07/02/2018 7 SPT-180205-1ta-2ta-3ta-4taAGPRE.xlsmrun 24 07/02/2018 7 SPT-180205-1ta-AGCOM.xlsmrun 25 14/02/2018 9 SPT-180212-1ep-2ep-3ep-AGPRE.xlsmrun 26 14/02/2018 9 SPT-180212-1ep-AGCOM.xlsmrun 27 21/02/2018 11 SPT-180219-1ta-AGPRE.xlsm

Table 33: RISE. Study3. Overview of accepted runs.

run ID Date passage file namerun 1 03/08/2018 29 agonism - DAT02-ASY06-prescreen-plate1-6.xlsmrun 2 03/08/2018 29 agonism - DAT02-ASY06-prescreen-plate7-11.xlsmrun 3 10/08/2018 30 agonism - DAT02-ASY06-prescreen2-plate 1 tm 6.xlsmrun 4 10/08/2018 30 agonism - DAT02-ASY06-prescreen2-plate7+8.xlsmrun 5 15/08/2018 31 agonism - DAT02-ASY06-prescreen3-plate 1 tm 6.xlsxrun 6 15/08/2018 31 agonism - DAT02-ASY06-prescreen3-plate 7+8.xlsmrun 7 23/08/2018 29 agonism - DAT02-ASY06-agonist-compr1-plate 1-4.xlsmrun 8 23/08/2018 29 agonism - DAT02-ASY06-agonist-compr2-plate 1-4.xlsmrun 9 17/10/2018 16 agonism - DAT02-ASY06-agonist-compr3-plate 1.xlsmrun 10 23/11/2018 27 agonism - DAT02-ASY06-agonist-compr3-plate 2-4.xlsm

Table 34: BDS. Study2. Overview of accepted runs.

42

Test item Code run IDs type1 CIT2CB run 5 run 8 run 13 COM COM COM2 CIT2XF run 5 run 8 run 13 COM COM COM3 CIT2AE run 2 run 7 run 11 PRE PRE PRE4 CIT2NX run 5 run 13 run 16 COM COM COM5 CIT2RD run 1 run 7 run 11 PRE PRE PRE6 CIT2YY run 1 run 7 run 11 PRE PRE PRE7 CIT2RK run 2 run 7 run 12 PRE PRE PRE8 CIT2XK run 2 run 6 run 10 PRE PRE PRE9 CIT2LK run 2 run 6 run 10 PRE PRE PRE10 CIT2GQ run 1 run 7 run 12 PRE PRE PRE11 CIT2ZT run 4 run 10 run 15 PRE PRE PRE12 CIT2DQ run 3 run 12 run 15 PRE PRE PRE13 CIT2TJ run 8 run 13 run 16 COM COM COM14 CIT2NN run 3 run 11 run 15 PRE PRE PRE15 CIT2JB run 3 run 14 run 18 PRE PRE PRE16 CIT2YW run 16 run 17 run 19 COM COM COM17 CIT2ML run 8 run 13 run 17 COM COM COM18 CIT2PY run 4 run 11 run 15 PRE PRE PRE19 CIT2HZ run 3 run 12 run 15 PRE PRE PRE20 CIT2TF run 3 run 12 run 15 PRE PRE PRE

Table 35: Citoxlab. Study2. Overview of three accepted runs per Test item.

Test item Code run IDs type1 ENV2VP run 3 run 5 run 7 COM COM COM2 ENV2XN run 3 run 5 run 7 COM COM COM3 ENV2HD run 1 run 2 run 5 PRE PRE COM4 ENV2ET run 3 run 5 run 7 COM COM COM5 ENV2YA run 2 run 4 run 6 PRE PRE PRE6 ENV2DF run 1 run 2 run 5 PRE PRE COM7 ENV2VZ run 1 run 2 run 4 PRE PRE PRE8 ENV2QF run 1 run 2 run 4 PRE PRE PRE9 ENV2ZR run 1 run 2 run 4 PRE PRE PRE10 ENV2GK run 1 run 2 run 4 PRE PRE PRE

Table 36: Envigo. Study2A. Overview of three accepted runs per Test item.

Test item Code run IDs type11 ENV3AT run 2 run 4 run 9 Pre PRE pre12 ENV3FJ run 1 run 4 run 9 PRE PRE pre13 ENV3UJ run 3 run 5 run 6 COM COM COM14 ENV3GU run 1 run 4 run 9 PRE PRE pre15 ENV3BH run 1 run 4 run 9 PRE PRE pre16 ENV3DX run 3 run 5 run 8 COM COM COM17 ENV3PU run 3 run 5 run 8 COM COM COM18 ENV3KU run 1 run 4 run 9 PRE PRE pre19 ENV3CK run 4 run 7 run 9 PRE PRE pre20 ENV3EH run 7 run 9 run 10 PRE pre PRE

Table 37: Envigo. Study2B. Overview of three accepted runs per Test item.

Test item Code run IDs type1 8WT run 3 run 5 run 7 COM COM COM2 10NM run 3 run 5 run 7 COM COM COM3 3HX run 3 run 5 run 7 COM COM COM4 1KX run 5 run 7 run 8 COM COM COM5 5MZ run 1 run 2 run 6 PRE PRE PRE6 7WS run 5 run 7 run 8 COM COM COM7 9YP run 1 run 4 run 6 PRE PRE PRE8 6NS run 1 run 4 run 6 PRE PRE PRE9 2SH run 1 run 2 run 6 PRE PRE PRE10 4LR run 5 run 7 run 8 COM COM COM

Table 38: RISE. Study2. Overview of three accepted runs per Test item.

43

Test item Code run IDs type11 11AM run 1 run 16 run 25 PRE PRE PRE12 18SJ run 2 run 5 run 25 PRE PRE PRE13 9NY run 13 run 17 run 19 COM COM COM14 22RU run 3 run 14 run 21 PRE PRE PRE15 28ZZ run 5 run 14 run 23 PRE PRE PRE16 3FA run 4 run 7 run 13 COM COM COM17 32BL run 15 run 19 run 22 COM COM COM18 30QT run 5 run 16 run 23 PRE PRE PRE19 20WZ run 3 run 14 run 18 PRE PRE PRE20 12ZV run 6 run 12 run 21 PRE PRE PRE21 24RY run 9 run 17 run 19 COM COM COM22 33TH run 8 run 10 run 23 PRE PRE PRE23 27YC run 5 run 14 run 23 PRE PRE PRE24 15SB run 3 run 12 run 21 PRE PRE PRE25 37VK run 11 run 15 run 19 COM COM COM26 13GZ run 2 run 12 run 21 PRE PRE PRE27 31RX run 6 run 8 run 20 PRE PRE PRE28 29DC run 10 run 16 run 25 PRE PRE PRE29 34VE run 11 run 15 run 19 COM COM COM30 7FK run 14 run 23 run 27 PRE PRE PRE31 1JA run 1 run 10 run 18 PRE PRE PRE32 19TM run 3 run 14 run 18 PRE PRE PRE33 5BR run 1 run 16 run 23 PRE PRE PRE34 36XY run 11 run 15 run 19 COM COM COM35 23QM run 6 run 8 run 18 PRE PRE PRE36 10JQ run 1 run 12 run 21 PRE PRE PRE37 4NQ run 1 run 10 run 21 PRE PRE PRE38 25RV run 9 run 24 run 26 COM COM COM39 16UA run 2 run 14 run 18 PRE PRE PRE40 8WJ run 1 run 10 run 18 PRE PRE PRE41 6MG run 1 run 10 run 18 PRE PRE PRE42 14FX run 2 run 12 run 21 PRE PRE PRE43 26XR run 1 run 2 run 3 PRE PRE PRE44 21DS run 3 run 14 run 21 PRE PRE PRE45 35VR run 15 run 19 run 22 COM COM COM46 2LU run 1 run 10 run 18 PRE PRE PRE47 17AR run 1 run 2 run 3 PRE PRE PRE

Table 39: RISE. Study3. Overview of three accepted runs per Test item.

Test item Code run IDs type1 BDS2SQ run 7 run 8 run 10 COM COM COM2 BDS2GG run 7 run 8 run 9 COM COM COM3 BDS2CG run 2 run 4 run 6 PRE PRE PRE4 BDS2LN run 7 run 8 run 10 COM COM COM5 BDS2CW run 2 run 3 run 5 PRE PRE PRE6 BDS2QX run 1 run 3 run 5 PRE PRE PRE7 BDS2MU run 1 run 3 run 5 PRE PRE PRE8 BDS2WW run 2 run 4 run 6 PRE PRE PRE9 BDS2YN run 2 run 3 run 5 PRE PRE PRE10 BDS2SD run 1 run 3 run 5 PRE PRE PRE11 BDS2XH run 1 run 3 run 5 PRE PRE PRE12 BDS2BU run 2 run 3 run 5 PRE PRE PRE13 BDS2VF run 7 run 8 run 10 COM COM COM14 BDS2AJ run 1 run 3 run 5 PRE PRE PRE15 BDS2AN run 2 run 4 run 6 PRE PRE PRE16 BDS2BG run 7 run 8 run 10 COM COM COM17 BDS2UE run 7 run 8 run 10 COM COM COM18 BDS2CM run 2 run 3 run 5 PRE PRE PRE19 BDS2NZ run 1 run 3 run 5 PRE PRE PRE20 BDS2MK run 1 run 3 run 5 PRE PRE PRE

Table 40: BDS. Study2. Overview of three accepted runs per Test item.

44

Test item Code stock conc (mgml)1 CIT2CB run 1: 5 run 5: 0.015 run 8: 0.015 run 13: 0.0152 CIT2XF run 2: 5 run 5: 0.15 run 8: 0.15 run 13: 0.153 CIT2AE run 2: 50 run 7: 50 cyt run 11: 154 CIT2NX run 1: 5 run 5: 5 run 13: 1.5 run 16: 55 CIT2RD run 1: 50 cyt run 7: 15 run 11: 156 CIT2YY run 1: 50 run 7: 50 run 11: 507 CIT2RK run 2: 15 cyt run 7: 4.5 cyt run 12: 1.358 CIT2XK run 2: 5 cyt run 6: 1.5 run 10: 1.59 CIT2LK run 2: 5 run 6: 5 run 10: 510 CIT2GQ run 1: 15 cyt run 7: 4.5 cyt run 12: 1.3511 CIT2ZT run 4: 5 run 10: 5 run 15: 512 CIT2DQ run 3: 50 run 12: 50 run 15: 5013 CIT2TJ run 4: 5 run 8: 0.015 run 13: 0.015 run 16: 0.01514 CIT2NN run 3: 15 run 11: 15 cyt run 15: 4.515 CIT2JB run 15: 50 cyt run 3: 50 cyt run 14: 15 cyt run 18: 4.516 CIT2YW run 4: 15 run 16: 15 run 17: 15 run 19: 1517 CIT2ML run 19: 5 cyt run 8: 1.5 run 13: 1.5 run 17: 1.518 CIT2PY run 4: 15 run 11: 15 run 15: 1519 CIT2HZ run 3: 50 run 12: 50 run 15: 5020 CIT2TF run 3: 50 run 12: 50 run 15: 50

Table 41: Citoxlab. Study2. Agonist testing. Overview of the highest tested concentrations in threeaccepted runs together with prescreen (where applicable). Last three colums reffer to three acceptedruns (either all prescreen or comprehensive). The first column refferes to the prescreen when 3accepted runs are comprehensive. Label "cyt" denotes cytotoxic concentrations.

Test item Code stock conc (mgml)1 ENV2VP run 1: 50 run 3: 0.015 run 5: 0.015 run 7: 0.0152 ENV2XN run 1: 5 run 3: 0.015 run 5: 0.015 run 7: 0.0153 ENV2HD run 1: 50 run 2: 50 run 5: 54 ENV2ET run 1: 5 run 3: 0.15 run 5: 0.15 run 7: 0.155 ENV2YA run 2: 50 run 4: 50 run 6: 506 ENV2DF run 1: 50 run 2: 50 run 5: 507 ENV2VZ run 1: 15 run 2: 1.5 run 4: 1.58 ENV2QF run 1: 15 run 2: 1.5 run 4: 1.59 ENV2ZR run 1: 15 run 2: 15 run 4: 1510 ENV2GK run 1: 15 run 2: 15 run 4: 15

Table 42: Envigo. Study2A. Agonist testing. Overview of the highest tested concentrations in threeaccepted runs together with prescreen (where applicable). Last three colums reffer to three acceptedruns (either all prescreen or comprehensive). The first column refferes to the prescreen when 3accepted runs are comprehensive. Label "cyt" denotes cytotoxic concentrations.

Test item Code stock conc (mgml)11 ENV3AT run 2: 15 run 4: 15 run 9: 1512 ENV3FJ run 1: 15 run 4: 15 run 9: 1513 ENV3UJ run 2: 5 run 3: 0.015 run 5: 0.015 run 6: 0.01514 ENV3GU run 1: 15 run 4: 15 run 9: 1515 ENV3BH run 1: 50 cyt run 4: 5 run 9: 516 ENV3DX run 2: 5 run 3: 0.15 run 5: 0.15 run 8: 1.517 ENV3PU run 1: 15 run 3: 4.5 run 5: 4.5 run 8: 1.518 ENV3KU run 1: 50 run 4: 50 run 9: 5019 ENV3CK run 4: 50 run 7: 50 run 9: 5020 ENV3EH run 7: 50 run 9: 50 run 10: 50

Table 43: Envigo. Study2B. Agonist testing. Overview of the highest tested concentrations in threeaccepted runs together with prescreen (where applicable). Last three colums reffer to three acceptedruns (either all prescreen or comprehensive). The first column refferes to the prescreen when 3accepted runs are comprehensive. Label "cyt" denotes cytotoxic concentrations.

45

Test item Code stock conc (mgml)1 8WT run 1: 15 run 3: 0.0045 run 5: 0.0045 run 7: 0.00452 10NM run 1: 5 run 3: 0.15 run 5: 0.045 run 7: 0.0453 3HX run 1: 15 run 3: 4.5 run 5: 4.5 run 7: 4.54 1KX run 1: 1.5 run 5: 1.5 run 7: 1.55 5MZ run 1: 15 run 2: 15 run 6: 156 7WS run 1: 50 run 5: 50 run 7: 50 run 8: 507 9YP run 1: 5 cyt run 4: 0.5 run 6: 0.58 6NS run 1: 5-5 cyt run 4: 0.5 run 6: 0.59 2SH run 1: 15 run 2: 15 run 6: 1510 4LR run 6: 15 cyt run 5: 1.5 run 7: 1.5 run 8: 1.5

Table 44: RISE. Study2. Agonist testing. Overview of the highest tested concentrations in threeaccepted runs together with prescreen (where applicable). Last three colums reffer to three acceptedruns (either all prescreen or comprehensive). The first column refferes to the prescreen when 3accepted runs are comprehensive. Label "cyt" denotes cytotoxic concentrations.

Test item Code stock conc (mgml)11 11AM run 1: 15 run 16: 15 run 25: 1512 18SJ run 2: 15 run 5: 15 run 25: 1513 9NY run 2: 5 run 13: 0.015 run 17: 0.015 run 19: 0.01514 22RU run 3: 5 run 14: 5 run 21: 515 28ZZ run 5: 50 cyt run 14: 5 run 23: 516 3FA run 1: 5 run 7: 5 run 13: 5 run 4: 517 32BL run 13: 5 cyt run 15: 1.5 run 19: 1.5 cyt run 22: 1.518 30QT run 5: 1.5 run 16: 1.5 run 23: 1.519 20WZ run 3: 50 run 14: 50 run 18: 5020 12ZV run 6: 1.5 run 12: 1.5 run 21: 1.521 24RY run 3: 1.5 run 9: 0.045 run 17: 0.045 run 19: 0.04522 33TH run 8: 15 cyt run 10: 1.5 run 23: 1.523 27YC run 5: 5 run 14: 5 run 23: 524 15SB run 3: 5 run 12: 5 run 21: 525 37VK run 21: 50 cyt run 11: 0.015 run 15: 0.015 run 19: 0.01526 13GZ run 2: 1.5 run 12: 1.5 run 21: 1.527 31RX run 6: 15 run 8: 15 run 20: 1528 29DC run 10: 0.15 run 16: 0.15 run 25: 0.1529 34VE run 25: 50 cyt run 11: 0.015 run 15: 0.015 run 19: 0.01530 7FK run 14: 0.005 run 23: 0.005 run 27: 0.00531 1JA run 1: 15 cyt run 10: 1.5 run 18: 1.532 19TM run 3: 50 run 14: 50 cyt run 18: 533 5BR run 1: 5 run 16: 5 run 23: 534 36XY run 8: 5 run 11: 0.05 run 15: 0.15 run 19: 0.1535 23QM run 6: 5 cyt run 8: 0.5 run 18: 0.536 10JQ run 1: 15 cyt run 12: 1.5 run 21: 1.537 4NQ run 1: 15 run 10: 15 run 21: 1538 25RV run 21: 15 cyt run 9: 0.045 run 24: 0.045 run 26: 0.04539 16UA run 2: 15 run 14: 15 run 18: 1540 8WJ run 1: 50 run 10: 50 run 18: 5041 6MG run 1: 15 run 10: 15 run 18: 1542 14FX run 2: 50 cyt run 12: 5 run 21: 543 26XR run 1: 1.5 run 2: 1.5 run 3: 1.544 21DS run 3: 50 cyt run 14: 5 run 21: 5 cyt45 35VR run 8: 5 run 22: 5 run 15: 5 run 19: 1.546 2LU run 1: 5 run 10: 5 run 18: 547 17AR run 1: 15 run 2: 15 run 3: 15

Table 45: RISE. Study3. Agonist testing. Overview of the highest tested concentrations in threeaccepted runs together with prescreen (where applicable). Last three colums reffer to three acceptedruns (either all prescreen or comprehensive). The first column refferes to the prescreen when 3accepted runs are comprehensive. Label "cyt" denotes cytotoxic concentrations.

46

Test item Code stock conc (mgml)1 BDS2SQ run 1: 50 run 7: 0.015 run 8: 0.015 run 10: 0.0152 BDS2GG run 1: 5 run 7: 0.015 run 8: 0.015 run 9: 0.0153 BDS2CG run 4: 50 run 6: 50 run 2: 504 BDS2LN run 1: 15 run 7: 0.45 run 8: 0.45 run 10: 0.455 BDS2CW run 3: 50 run 5: 50 run 2: 506 BDS2QX run 3: 50 run 5: 50 run 1: 507 BDS2MU run 3: 15 run 5: 15 run 1: 158 BDS2WW run 4: 15 run 6: 15 run 2: 159 BDS2YN run 3: 15 run 5: 15 run 2: 1510 BDS2SD run 3: 15 run 5: 15 run 1: 1511 BDS2XH run 3: 15 run 5: 15 run 1: 1512 BDS2BU run 3: 50 run 5: 50 run 2: 5013 BDS2VF run 2: 5 run 7: 0.015 run 8: 0.015 run 10: 0.01514 BDS2AJ run 3: 15 run 5: 15 run 1: 1515 BDS2AN run 4: 50 run 6: 50 run 2: 5016 BDS2BG run 1: 5 run 7: 0.15 run 8: 0.15 run 10: 0.1517 BDS2UE run 2: 15 run 7: 4.5 run 8: 4.5 run 10: 4.518 BDS2CM run 3: 15 run 5: 15 run 2: 1519 BDS2NZ run 3: 50 run 5: 50 run 1: 5020 BDS2MK run 3: 50 run 5: 50 run 1: 50

Table 46: BDS. Study2. Agonist testing. Overview of the highest tested concentrations in threeaccepted runs together with prescreen (where applicable). Last three colums reffer to three acceptedruns (either all prescreen or comprehensive). The first column refferes to the prescreen when 3accepted runs are comprehensive. Label "cyt" denotes cytotoxic concentrations.

A.2 Antagonist testing

run ID Date passage file namerun 1 29/08/2018 9 Citoxlab-45631 RD-ANT03-20180828-PRE-second serie-DAT04-ASY06.xlsmrun 2 30/08/2018 9 Citoxlab-45631 RD-ANT04-20180829-PRE-first serie-DAT04-ASY06.xlsmrun 3 30/08/2018 9 Citoxlab-45631 RD-ANT04-20180829-PRE-second serie-DAT04-ASY06.xlsmrun 4 12/09/2018 13 Citoxlab-DAT04-ASY06-v04-ANT07-20180911-PRE-first serie.xlsmrun 5 12/09/2018 13 Citoxlab-DAT04-ASY06-v04-ANT07–20180911-PRE-second serie.xlsmrun 6 26/09/2018 17 Citoxlab-DAT05-ASY06-v04-45631 RD-20180925-COM-ANT11-first serie.xlsmrun 7 26/09/2018 17 Citoxlab-DAT05-ASY06-v04-45631 RD-20180925-COM-ANT11-second serie-retreated.xlsmrun 8 26/09/2018 17 Citoxlab-DAT05-ASY06-v04-45631 RD-20180925-COM-ANT11-third serie.xlsmrun 9 04/10/2018 19 Citoxlab-DAT05-ASY06-v04-20181003-COM-45631RD-ANT14-first serie.xlsmrun 10 04/10/2018 19 Citoxlab-DAT05-ASY06-v04-20181003-COM-45631RD-ANT14-second serie.xlsmrun 11 04/10/2018 19 Citoxlab-DAT05-ASY06-v04-20181003-COM-45631RD-ANT14-third serie.xlsmrun 12 10/10/2018 21 Citoxlab-DAT04-ASY06-v04-45631 RD-20181009-PRE-ANT15-second serie.xlsmrun 13 18/10/2018 23 Citoxlab-DAT04-ASY06-v05-45631RD-20181016-PRE-ANT18-first serie.xlsmrun 14 18/10/2018 23 Citoxlab-DAT04-ASY06-v05-45631RD-20181016-PRE-ANT18-second serie.xlsmrun 15 25/10/2018 25 Citoxlab-DAT04-ASY06-v05-45631 RD-20181024-PRE-ANT23.xlsmrun 16 31/10/2018 27 Citoxlab-DAT05-ASY06-v05-45631 RD-20181030-COM-ANT25-first serie.xlsmrun 17 31/10/2018 27 Citoxlab-DAT05-ASY06-v05-45631 RD-20181030-COM-ANT25-fourth serie.xlsmrun 18 31/10/2018 27 Citoxlab-DAT05-ASY06-v05-45631 RD-20181030-COM-ANT25-second serie.xlsmrun 19 31/10/2018 27 Citoxlab-DAT05-ASY06-v05-45631 RD-20181030-COM-ANT25-third serie.xlsmrun 20 07/11/2018 29 Citoxlab-DAT05-ASY06-v05-45631 RD-20181106-COM-ANT26-first serie.xlsmrun 21 07/11/2018 29 Citoxlab-DAT05-ASY06-v05-45631 RD-20181106-COM-ANT26-second serie.xlsmrun 22 07/11/2018 29 Citoxlab-DAT05-ASY06-v05-45631 RD-20181106-COM-ANT26-third serie.xlsm

Table 47: Citoxlab. Study2. Antagonist testing. Overview of accepted runs.

run ID Date passage file namerun 1 22/02/2017 19 ENV-pAN01-received 2017 03 21.xlsmrun 2 01/03/2017 21 ENV-pAN02-received 2017 03 21.xlsmrun 3 15/03/2017 25 ENV-pAN03 Invalid.xlsmrun 4 29/03/2017 29 ENV-pAN04.xlsmrun 5 05/04/2017 311 ENV-cAN01.xlsmrun 6 12/04/2017 251 ENV-cAN02.xlsmrun 7 27/04/2017 31 ENV-cAN03.xlsm

Table 48: Envigo. Study2A. Antagonist testing. Overview of accepted runs.

47

run ID Date passage file namerun 1 23/08/2017 5 ENV2B-pAN01.xlsmrun 2 27/09/2017 14 ENV2B-pAN03.xlsmrun 3 04/10/2017 16 ENV2B-pAN04.xlsmrun 4 16/11/2017 28 ENV2B-pAN06.xlsmrun 5 16/11/2017 28 ENV2B-cAN01.xlsmrun 6 23/11/2017 3 ENV2B-cAN02.xlsmrun 7 30/11/2017 5 ENV2B-cAN03.xlsmrun 8 13/12/2017 9 ENV2B-pAN07.xlsmrun 9 13/12/2017 9 ENV2B-cAN04.xlsmrun 10 15/02/2018 27 ENV2B-cAN06.xlsmrun 11 22/02/2018 29 ENV2B-cAN07.xlsm

Table 49: Envigo. Study2B. Antagonist testing. Overview of accepted runs.

run ID Date passage file namerun 1 02/11/2016 7 SPT-161031-1ep-2ep-3ep-4ep-5ep-6ep-ANPRE.xlsmrun 2 09/11/2016 9 SPT-161107-7jj-8jj-ANPRE.xlsmrun 3 09/11/2016 9 SPT-161109-7jj-9jj-10jj-11jj-12jj-ANCOM.xlsmrun 4 16/11/2016 11 SPT-161114-8lb-11lb-12lb-ANPRE.xlsmrun 5 16/11/2016 11 SPT-161114-8lb-9lb-10lb-ANCOM.xlsmrun 6 30/11/2016 15 SPT-161128-6ep-7ep-8ep-ANCOM.xlsmrun 7 07/12/2016 17 SPT-161205-7kf-12kf-ANPRE.xlsmrun 8 07/12/2016 17 SPT-161205-7kf-8kf-9kf-10kf-11kf-ANCOM.xlsmrun 9 14/12/2016 19 SPT-161212-10ep-12ep-ANPRE.xlsmrun 10 14/12/2016 19 SPT-161212-10ep-11ep-ANCOM.xlsmrun 11 14/12/2016 19 SPT-161212-4ep-5ep-6ep-7ep-8ep-9ep-ANCOM.xlsm

Table 50: RISE. Study2. Antagonist testing. Overview of accepted runs.

run ID Date passage file namerun 1 24/05/2017 3 SPT-170524-7ep-8ep-9ep-10ep-11ep-12ep-ANPRE.xlsmrun 2 21/06/2017 11 SPT-170619-5ep-6ep-7ep-ANTCOM.xlsmrun 3 21/06/2017 11 SPT-170619-5ep-8ep-9ep-ANTPRE.xlsmrun 4 28/06/2017 13 SPT-170626-6ep-7ep-8ep-ANTCOM.xlsmrun 5 28/06/2017 13 SPT-170626-6ep-9ep-10ep-11ep-ANTPRE.xlsmrun 6 12/07/2017 17 SPT-170710-5lb-6lb-7lb-ANCOM.xlsmrun 7 12/07/2017 17 SPT-170710-5lb-8lb-9lb-10lb-ANPRE.xlsmrun 8 13/09/2017 3 SPT-170911-5lb-6lb-7lb-ANTCOM.xlsmrun 9 13/09/2017 3 SPT-170911-5lb-8lb-9lb-10lb-ANTPRE.xlsmrun 10 04/10/2017 9 SPT-171002-12lb-13lb-14lb-15lb-16lb-17lb-ANTCOM.xlsmrun 11 04/10/2017 9 SPT-171002-7lb-8lb-9lb-10lb-ANTPRE.xlsmrun 12 18/10/2017 13 SPT-171016-4ep-5ep-6ep-7ep-8ep-9ep-ANTCOM.xlsmrun 13 08/11/2017 19 SPT-171106-13ta-14ta-15ta-16ta-17ta-18ta-ANTCOM.xlsmrun 14 08/11/2017 19 SPT-171106-7ta-8ta-9ta-10ta-11ta-ANTCOM-invalid.xlsmrun 15 22/11/2017 23 SPT-171120-13jj-14jj-15jj-16jj-17jj-ANTPRE.xlsmrun 16 22/11/2017 23 SPT-171120-7jj-8jj-9jj-10jj-11jj-12jj-ANTCOM.xlsmrun 17 29/11/2017 25 SPT-171127-13ta-14ta-15ta-16ta-17ta-18ta-ANTCOM-invalid.xlsmrun 18 29/11/2017 25 SPT-171127-7ta-10ta-11ta-12ta-ANTPRE-invalid.xlsmrun 19 29/11/2017 25 SPT-171127-7ta-8ta-9ta-ANTCOM-invalid.xlsmrun 20 24/01/2018 3 SPT-180122-13ep-14ep-15ep-16ep-17ep-18ep-ANTCOM.xlsmrun 21 24/01/2018 3 SPT-180122-7ep-8ep-9ep-10ep-11ep-12ep-ANTPRE.xlsmrun 22 31/01/2018 5 SPT-180129-13lb-14lb-15lb-16lb-17lb-ANTCOM.xlsmrun 23 31/01/2018 5 SPT-180129-13lb-18lb-ANTPRE.xlsmrun 24 31/01/2018 5 SPT-180129-7lb-8lb-9lb-10lb-12lb-ANTCOM.xlsmrun 25 07/02/2018 7 SPT-180205-19ta-14ta-15ta-16ta-17ta-18ta-ANCOM-.xlsmrun 26 07/02/2018 7 SPT-180205-5ta-6ta-ANPRE.xlsmrun 27 07/02/2018 7 SPT-180205-7ta-8ta-9ta-10ta-11ta-12ta-ANCOM-.xlsmrun 28 14/02/2018 9 SPT-180212-13ep-14ep-15ep-16ep-17ep-18ep-ANCOM.xlsmrun 29 14/02/2018 9 SPT-180212-4ep-5ep-6ep-ANPRE.xlsmrun 30 14/02/2018 9 SPT-180212-7ep-8ep-9ep-10ep-11ep-12ep-ANCOM.xlsmrun 31 21/02/2018 11 SPT-180219-12ta-13ta-14ta-15ta-16ta-17ta-ANCOM.xlsmrun 32 21/02/2018 11 SPT-180219-2ta-3ta-4ta-ANPRE.xlsmrun 33 21/02/2018 11 SPT-180219-2ta-5ta-ANCOM.xlsmrun 34 21/02/2018 11 SPT-180219-6ta-7ta-8ta-9ta-10ta-11ta-ANCOM.xlsm

Table 51: RISE. Study3. Antagonist testing. Overview of accepted runs.

48

run ID Date passage file namerun 1 16/08/2018 33 antagonism - DAT04-ASY06-prescreen1-anta-plate1-6.xlsmrun 2 16/08/2018 33 antagonism - DAT04-ASY06-prescreen1-anta-plate7-11.xlsmrun 3 17/10/2018 16 antagonism - DAT04-ASY06-prescreen2-anta-plate1-6.xlsmrun 4 17/10/2018 16 antagonism - DAT04-ASY06-prescreen3-anta-plate1-6.xlsmrun 5 19/10/2018 17 antagonism - DAT05-ASY06-anta-comp1-plate1-6.xlsmrun 6 19/10/2018 17 antagonism - DAT05-ASY06-anta-comp1-plate7-12.xlsmrun 7 24/10/2018 18 antagonism - DAT05-ASY06-anta-comp2-plate1-6.xlsmrun 8 24/10/2018 18 antagonism - DAT05-ASY06-anta-comp2-plate7-12.xlsmrun 9 24/10/2018 18 antagonism - DAT05-ASY06-anta-comp3-plate1-6.xlsmrun 10 24/10/2018 18 antagonism - DAT05-ASY06-anta-comp3-plate7-12.xlsmrun 11 28/11/2018 28 antagonism - DAT05-ASY06-anta-comp1-remeasure-cm-cw-cg-sd.xlsmrun 12 28/11/2018 28 antagonism - DAT05-ASY06-anta-comp2-remeasure-sd-aj-cm-ue-cg.xlsmrun 13 28/11/2018 28 antagonism - DAT05-ASY06-anta-comp3-her-CW.xlsmrun 14 03/12/2018 28 antagonism - DAT05-ASY06-anta-comp1-remeasure2-cg-sd.xlsmrun 15 03/12/2018 28 antagonism - DAT05-ASY06-anta-comp2-remeasure-aj-cg.xlsmrun 16 03/12/2018 28 antagonism - DAT05-ASY06-anta-comp3-her-CG-SD.xlsmrun 17 03/12/2018 28 antagonism - DAT05-ASY06-anta-comp3-her-SD.xlsm

Table 52: BDS. Study2. Antagonist testing. Overview of accepted runs.

49

Test item Code run IDs type1 CIT2CB run 1 run 5 run 13 PRE PRE PRE2 CIT2XF run 4 run 13 run 15 PRE PRE PRE3 CIT2AE run 10 run 17 run 20 COM COM COM4 CIT2NX run 1 run 5 run 13 PRE PRE PRE5 CIT2RD run 7 run 9 run 16 COM COM COM6 CIT2YY run 7 run 11 run 16 COM COM COM7 CIT2RK run 5 run 14 run 15 PRE PRE PRE8 CIT2XK run 5 run 12 run 15 PRE PRE PRE9 CIT2LK run 5 run 13 run 15 PRE PRE PRE10 CIT2GQ run 8 run 18 run 20 COM COM COM11 CIT2ZT run 3 run 12 run 14 PRE PRE PRE12 CIT2DQ run 2 run 12 run 14 PRE PRE PRE13 CIT2TJ run 3 run 12 run 13 PRE PRE PRE14 CIT2NN run 9 run 19 run 21 COM COM COM15 CIT2JB run 10 run 18 run 22 COM COM COM16 CIT2YW run 3 run 12 run 14 PRE PRE PRE17 CIT2ML run 11 run 18 run 21 COM COM COM18 CIT2PY run 10 run 19 run 22 COM COM COM19 CIT2HZ run 9 run 16 run 20 COM COM COM20 CIT2TF run 11 run 17 run 21 COM COM COM

Table 53: Citoxlab. Study2. Antagonist testing. Overview of three accepted runs per Test item.

Test item Code run IDs type1 ENV2VP run 5 run 6 run 7 COM COM COM2 ENV2XN run 1 run 2 run 4 PRE PRE PRE3 ENV2HD run 5 run 6 run 7 COM COM COM4 ENV2ET run 1 run 2 run 4 PRE PRE PRE5 ENV2YA run 5 run 6 run 7 COM COM COM6 ENV2DF run 5 run 6 run 7 COM COM COM7 ENV2VZ run 1 run 2 run 4 PRE PRE PRE8 ENV2QF run 1 run 2 run 4 PRE PRE PRE9 ENV2ZR run 1 run 2 run 4 PRE PRE PRE10 ENV2GK run 5 run 6 run 7 COM COM COM

Table 54: Envigo. Study2A. Antagonist testing. Overview of three accepted runs per Test item.

Test item Code run IDs type11 ENV3AT run 1 run 2 run 3 PRE PRE PRE12 ENV3FJ run 1 run 2 run 3 PRE PRE PRE13 ENV3UJ run 2 run 3 run 8 PRE PRE PRE14 ENV3GU run 5 run 6 run 7 COM COM COM15 ENV3BH run 5 run 6 run 7 COM COM COM16 ENV3DX run 2 run 3 run 8 PRE PRE PRE17 ENV3PU run 9 run 10 run 11 COM COM COM18 ENV3KU run 5 run 6 run 7 COM COM COM19 ENV3CK run 1 run 2 run 3 PRE PRE PRE20 ENV3EH run 6 run 9 run 10 COM COM COM

Table 55: Envigo. Study2B. Antagonist testing. Overview of three accepted runs per Test item.

Test item Code run IDs type1 08WT run 1 run 4 run 9 PRE PRE PRE2 10NM run 1 run 7 run 9 PRE PRE PRE3 03HX run 3 run 6 run 11 COM COM COM4 01KX run 6 run 8 run 11 COM COM COM5 05MZ run 3 run 5 run 11 COM COM COM6 07WS run 5 run 8 run 10 COM COM COM7 09YP run 1 run 4 run 7 PRE PRE PRE8 06NS run 1 run 2 run 4 PRE PRE PRE9 02SH run 3 run 8 run 11 COM COM COM10 04LR run 3 run 8 run 11 COM COM COM

Table 56: RISE. Study2. Antagonist testing. Overview of three accepted runs per Test item.

50

Test item Code run IDs type11 11AM run 1 run 15 run 29 PRE PRE PRE12 18SJ run 7 run 15 run 29 PRE PRE PRE13 09NY run 15 run 21 run 26 PRE PRE PRE14 22RU run 13 run 22 run 34 COM COM COM15 28ZZ run 13 run 25 run 31 COM COM COM16 03FA run 1 run 7 run 9 PRE PRE PRE17 32BL run 20 run 22 run 31 COM COM COM18 30QT run 13 run 16 run 25 COM COM COM19 20WZ run 20 run 25 run 34 COM COM COM20 12ZV run 12 run 24 run 28 COM COM COM21 24RY run 5 run 21 run 29 PRE PRE PRE22 33TH run 16 run 25 run 31 COM COM COM23 27YC run 13 run 25 run 31 COM COM COM24 15SB run 12 run 22 run 34 COM COM COM25 37VK run 11 run 21 run 32 PRE PRE PRE26 13GZ run 12 run 24 run 28 COM COM COM27 31RX run 9 run 21 run 32 PRE PRE PRE28 29DC run 11 run 15 run 29 PRE PRE PRE29 34VE run 11 run 15 run 21 PRE PRE PRE30 07FK run 20 run 27 run 30 COM COM COM31 01JA run 10 run 30 run 33 COM COM COM32 19TM run 5 run 21 run 32 PRE PRE PRE33 05BR run 1 run 15 run 26 PRE PRE PRE34 36XY run 16 run 20 run 31 COM COM COM35 23QM run 9 run 21 run 29 PRE PRE PRE36 10JQ run 12 run 24 run 28 COM COM COM37 04NQ run 10 run 24 run 30 COM COM COM38 25RV run 7 run 21 run 26 PRE PRE PRE39 16UA run 20 run 27 run 34 COM COM COM40 08WJ run 10 run 27 run 28 COM COM COM41 06MG run 10 run 16 run 30 COM COM COM42 14FX run 12 run 24 run 28 COM COM COM43 26XR run 2 run 4 run 8 COM COM COM44 21DS run 13 run 22 run 34 COM COM COM45 35VR run 11 run 21 run 23 PRE PRE PRE46 02LU run 10 run 27 run 30 COM COM COM47 17AR run 2 run 4 run 6 COM COM COM

Table 57: RISE. Study3. Antagonist testing. Overview of three accepted runs per Test item.

Test item Code run IDs type1 BDS2SQ run 1 run 3 run 4 PRE PRE PRE2 BDS2GG run 1 run 3 run 4 PRE PRE PRE3 BDS2CG run 10 run 14 run 16 COM COM COM4 BDS2LN run 1 run 3 run 4 PRE PRE PRE5 BDS2CW run 8 run 11 run 13 COM COM COM6 BDS2QX run 5 run 7 run 9 COM COM COM7 BDS2MU run 1 run 3 run 4 PRE PRE PRE8 BDS2WW run 2 run 3 run 4 PRE PRE PRE9 BDS2YN run 2 run 3 run 4 PRE PRE PRE10 BDS2SD run 11 run 14 run 17 COM COM COM11 BDS2XH run 1 run 3 run 4 PRE PRE PRE12 BDS2BU run 2 run 3 run 4 PRE PRE PRE13 BDS2VF run 2 run 3 run 4 PRE PRE PRE14 BDS2AJ run 5 run 9 run 15 COM COM COM15 BDS2AN run 6 run 8 run 10 COM COM COM16 BDS2BG run 1 run 3 run 4 PRE PRE PRE17 BDS2UE run 6 run 10 run 12 COM COM COM18 BDS2CM run 10 run 11 run 12 COM COM COM19 BDS2NZ run 5 run 7 run 9 COM COM COM20 BDS2MK run 5 run 7 run 9 COM COM COM

Table 58: BDS. Study2. Antagonist testing. Overview of three accepted runs per Test item.

51

Test item Code stock conc (mgml)1 CIT2CB run 1: 5 run 5: 5 run 13: 52 CIT2XF run 4: 5 run 13: 5 run 15: 53 CIT2AE run 15: 50 cyt run 10: 15 run 17: 15 run 20: 154 CIT2NX run 1: 5 run 5: 5 run 13: 55 CIT2RD run 13: 50 cyt run 7: 15 run 9: 15 run 16: 156 CIT2YY run 1: 50 run 7: 1.5 run 11: 1.5 run 16: 1.57 CIT2RK run 5: 15 cyt run 14: 4.5 cyt run 15: 1.358 CIT2XK run 5: 5 cyt run 12: 1.5 run 15: 1.59 CIT2LK run 5: 5 run 13: 5 run 15: 510 CIT2GQ run 15: 15 cyt run 8: 0.45 run 18: 0.45 run 20: 0.4511 CIT2ZT run 3: 5 run 12: 5 run 14: 512 CIT2DQ run 2: 50 run 12: 50 run 14: 5013 CIT2TJ run 3: 5 run 12: 5 run 13: 514 CIT2NN run 2: 15 run 9: 4.5 run 19: 4.5 run 21: 4.515 CIT2JB run 21: 50 cyt run 10: 15 run 18: 15 cyt run 22: 516 CIT2YW run 3: 15 run 12: 15 run 14: 1517 CIT2ML run 14: 5 cyt run 11: 1.5 run 18: 1.5 run 21: 1.518 CIT2PY run 2: 15 run 10: 15 run 19: 15 run 22: 1519 CIT2HZ run 3: 50 run 9: 50 run 16: 50 run 20: 5020 CIT2TF run 3: 50 run 11: 1.5 run 17: 1.5 run 21: 1.5

Table 59: Citoxlab. Study2. Antagonist testing. Overview of the highest tested concentrations inthree accepted runs together with prescreen (where applicable). Last three colums reffer to threeaccepted runs (either all prescreen or comprehensive). The first column refferes to the prescreenwhen 3 accepted runs are comprehensive. Label "cyt" denotes cytotoxic concentrations.

Test item Code stock conc (mgml)1 ENV2VP run 1: 50 run 5: 50 run 6: 50 run 7: 502 ENV2XN run 1: 5 run 2: 5 run 4: 53 ENV2HD run 4: 50 cyt run 5: 1.5 run 6: 0.45 run 7: 0.454 ENV2ET run 1: 5 run 2: 5 run 4: 55 ENV2YA run 1: 50 run 5: 15 run 6: 15 run 7: 156 ENV2DF run 1: 50 run 5: 1.5 run 6: 1.5 run 7: 1.57 ENV2VZ run 1: 15 cyt run 2: 1.5 run 4: 1.58 ENV2QF run 1: 15 cyt run 2: 1.5 run 4: 1.59 ENV2ZR run 1: 15 run 2: 15 run 4: 1510 ENV2GK run 1: 15 run 5: 0.45 run 6: 0.45 run 7: 0.45

Table 60: Envigo. Study2A. Antagonist testing. Overview of the highest tested concentrations inthree accepted runs together with prescreen (where applicable). Last three colums reffer to threeaccepted runs (either all prescreen or comprehensive). The first column refferes to the prescreenwhen 3 accepted runs are comprehensive. Label "cyt" denotes cytotoxic concentrations.

Test item Code stock conc (mgml)11 ENV3AT run 1: 15 run 2: 15 run 3: 1512 ENV3FJ run 1: 15 run 2: 15 run 3: 1513 ENV3UJ run 2: 5 run 3: 5 run 8: 514 ENV3GU run 1: 15 run 5: 4.5 run 6: 4.5 run 7: 4.515 ENV3BH run 1: 5 run 5: 5 run 6: 5 run 7: 516 ENV3DX run 2: 5 run 3: 5 run 8: 517 ENV3PU run 1: 3 run 9: 0.09 run 10: 0.09 run 11: 0.0918 ENV3KU run 11: 50 cyt run 5: 50 run 6: 50 run 7: 5019 ENV3CK run 1: 50 run 2: 50 run 3: 5020 ENV3EH run 4: 5 run 6: 0.15 run 9: 0.15 run 10: 0.15

Table 61: Envigo. Study2B. Antagonist testing. Overview of the highest tested concentrations inthree accepted runs together with prescreen (where applicable). Last three colums reffer to threeaccepted runs (either all prescreen or comprehensive). The first column refferes to the prescreenwhen 3 accepted runs are comprehensive. Label "cyt" denotes cytotoxic concentrations.

52

Test item Code stock conc (mgml)1 08WT run 1: 15 cyt run 4: 1.5 run 9: 1.52 10NM run 1: 5 run 7: 5 run 9: 53 03HX run 9: 15 cyt run 3: 0.45 run 6: 0.45 run 11: 0.454 01KX run 1: 1.5 run 6: 0.045 run 8: 0.045 run 11: 0.0455 05MZ run 1: 15 run 3: 15 run 5: 15 run 11: 156 07WS run 1: 50 run 5: 1.5 run 8: 1.5 run 10: 1.57 09YP run 1: 5 cyt run 4: 0.5 run 7: 0.58 06NS run 1: 5 cyt run 2: 0.5 run 4: 0.59 02SH run 1: 15 run 3: 15 run 8: 15 run 11: 1510 04LR run 11: 15 cyt run 3: 0.45 run 8: 0.45 run 11: 0.45

Table 62: RISE. Study2. Antagonist testing. Overview of the highest tested concentrations in threeaccepted runs together with prescreen (where applicable). Last three colums reffer to three acceptedruns (either all prescreen or comprehensive). The first column refferes to the prescreen when 3accepted runs are comprehensive. Label "cyt" denotes cytotoxic concentrations.

Test item Code stock conc (mgml)11 11AM run 1: 15 run 15: 15 run 29: 1512 18SJ run 7: 15 run 15: 15 run 29: 1513 09NY run 15: 5 run 21: 5 run 26: 514 22RU run 5: 5 run 13: 5 run 22: 1.5 run 34: 1.515 28ZZ run 7: 50 cyt run 13: 15 cyt run 25: 5 run 31: 516 03FA run 1: 5 run 7: 5 run 9: 517 32BL run 9: 5 cyt run 20: 0.15 run 22: 0.15 run 31: 0.1518 30QT run 7: 1.5 run 13: 1.5 run 16: 1.5 run 25: 1.519 20WZ run 5: 50 run 20: 50 run 25: 50 run 34: 5020 12ZV run 9: 1.5 run 12: 0.45 run 24: 0.45 run 28: 0.4521 24RY run 5: 1.5 run 21: 1.5 run 29: 1.522 33TH run 11: 15 run 16: 0.15 run 25: 0.15 run 31: 0.1523 27YC run 7: 5 run 13: 5 run 25: 5 run 31: 524 15SB run 5: 5 run 12: 5 run 22: 5 run 34: 525 37VK run 11: 50 run 21: 50 cyt run 32: 526 13GZ run 3: 1.5 run 12: 1.5 run 24: 1.5 run 28: 1.527 31RX run 9: 15 run 21: 15 run 32: 1528 29DC run 11: 0.15 run 15: 0.1529 34VE run 11: 50 run 15: 50 cyt run 21: 530 07FK run 9: 0.05-5 cyt run 20: 0.015 cyt run 27: 0.005 run 30: 0.00531 01JA run 30: 15 cyt run 10: 4.5 cyt run 30: 1.5 run 33: 1.532 19TM run 5: 50 run 21: 50 cyt run 32: 533 05BR run 1: 5 run 15: 5 run 26: 5 cyt34 36XY run 11: 5 run 16: 5 run 20: 5 run 31: 535 23QM run 9: 5 cyt run 21: 0.5 run 29: 0.536 10JQ run 29: 15 cyt run 12: 0.45 run 24: 0.15 run 28: 0.1537 04NQ run 1: 15 run 10: 15 run 24: 15 run 30: 1538 25RV run 7: 15 cyt run 21: 1.5 run 26: 1.539 16UA run 3: 15 run 20: 15 run 27: 15 run 34: 1540 08WJ run 1: 50 run 10: 15 run 27: 15 run 28: 1541 06MG run 1: 15 run 10: 15 run 16: 15 run 30: 1542 14FX run 30: 50 cyt run 12: 15 run 24: 15 run 28: 1543 26XR run 1: 1.5 run 2: 1.5 run 4: 1.5 run 8: 1.544 21DS run 8: 50 cyt run 13: 5 cyt run 22: 1.5 run 34: 1.545 35VR run 11: 5 run 21: 5 run 23: 546 02LU run 1: 5 run 10: 5 run 27: 5 run 30: 1.547 17AR run 1: 15 run 2: 1.5 run 4: 1.5 run 6: 1.5

Table 63: RISE. Study3. Antagonist testing. Overview of the highest tested concentrations in threeaccepted runs together with prescreen (where applicable). Last three colums reffer to three acceptedruns (either all prescreen or comprehensive). The first column refferes to the prescreen when 3accepted runs are comprehensive. Label "cyt" denotes cytotoxic concentrations.

53

Test item Code stock conc (mgml)1 BDS2SQ run 1: 50 run 3: 50 cyt run 4: 50 cyt2 BDS2GG run 1: 5 run 3: 5 run 4: 53 BDS2CG run 2: 50 run 14: 1.5 run 16: 15 run 10: 1.54 BDS2LN run 1: 15 run 3: 15 run 4: 155 BDS2CW run 4: 50 cyt run 11: 15 run 8: 15 run 13: 156 BDS2QX run 1: 50 run 5: 1.5 run 7: 1.5 run 9: 1.57 BDS2MU run 1: 15 cyt run 3: 15 cyt run 4: 15 cyt8 BDS2WW run 2: 15 cyt run 3: 15 cyt run 4: 15 cyt9 BDS2YN run 2: 15 run 3: 15 run 4: 1510 BDS2SD run 1: 15 run 14: 0.5 run 17: 15 run 11: 0.511 BDS2XH run 1: 15 run 3: 15 run 4: 1512 BDS2BU run 2: 50 run 3: 50 run 4: 5013 BDS2VF run 2: 5 run 3: 5 run 4: 514 BDS2AJ run 1: 15 run 5: 4.5 run 15: 4.5 run 9: 4.515 BDS2AN run 15: 50 cyt run 6: 15 run 8: 15 run 10: 1516 BDS2BG run 1: 5 run 3: 5 run 4: 517 BDS2UE run 2: 15 run 6: 0.45 run 12: 0.45 run 10: 0.4518 BDS2CM run 2: 15 run 12: 45 run 10: 4519 BDS2NZ run 1: 50 run 5: 150 run 7: 150 run 9: 15020 BDS2MK run 1: 50 run 5: 1.5 run 7: 1.5 run 9: 1.5

Table 64: BDS. Study2. Antagonist testing. Overview of the highest tested concentrations in threeaccepted runs together with prescreen (where applicable). Last three colums reffer to three acceptedruns (either all prescreen or comprehensive). The first column refferes to the prescreen when 3accepted runs are comprehensive. Label "cyt" denotes cytotoxic concentrations.

54

Appendix B Acceptance criteria

B.1 Agonist testing

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DHT, run ID: 7

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DHT, run ID: 9 10

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DHT, run ID: 11

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DHT, run ID: 12

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DHT, run ID: 13 14

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DHT, run ID: 15

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DHT, run ID: 16

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DHT, run ID: 17 18

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Figure 24: Citoxlab,Study2 DHT responses.

55

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DHT, run ID: 1

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DHT, run ID: 7 4

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DHT, run ID: 3 6

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DHT, run ID: 8

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DHT, run ID: 9

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Figure 25: Envigo,Study2A DHT responses.

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Figure 26: Envigo,Study2B DHT responses.

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Figure 27: RISE,Study2 DHT responses.

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Figure 28: RISE,Study3 DHT responses.

58

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Figure 29: BDS,Study2 DHT responses.

59

Induction factor Z factorrun ID plate 1 plate 2 plate 3 plate 4 plate 1 plate 2 plate 3 plate 4run 1 160.4 169.5 169.6 0.77 0.92 0.91run 2 149.8 155 136.9 0.91 0.81 0.87run 3 156.1 144.2 166.8 0.9 0.88 0.88run 4 140.9 144.8 135.8 0.77 0.76 0.89run 5 151.7 178.6 0.9 0.91run 6 151.7 179.5 0.9 0.86run 7 155.3 151.4 145.3 0.9 0.88 0.9run 8 98.9 82.9 91.9 0.9 0.93 0.92run 9 92.3 0.89run 10 92.3 63.5 67.1 0.89 0.88 0.91run 11 137 129.7 119.3 0.96 0.88 0.86run 12 128.1 116.5 117.1 0.95 0.86 0.87run 13 64.9 55.8 59.3 54.4 0.88 0.88 0.82 0.89run 14 64.9 54.4 0.88 0.89run 15 156.9 145.7 140.9 131.9 0.82 0.89 0.86 0.87run 16 207.2 154.1 0.28 0.84run 17 110.4 102.9 0.76 0.86run 18 110.4 0.76run 19 150.8 0.8

Table 65: Citoxlab. Study2. Acceptance criteria: Induction factor, Z-factor.

Induction factor Z factorrun ID plate 1 plate 2 plate 3 plate 4 plate 5 plate 1 plate 2 plate 3 plate 4 plate 5run 1 86.1 96.7 88.6 98.1 98.1 0.96 0.8 0.9 0.77 0.78run 2 38.9 40.4 44.2 38.1 0.41 0.8 0.79 0.83run 3 38.9 41.3 64.2 0.41 0.82 0.8run 4 72.8 66.7 61.4 0.71 0.79 0.81run 5 72.8 76.6 56.9 65.7 0.71 0.88 0.83 0.89run 6 70.6 0.78run 7 70.6 63.9 67.9 0.78 0.76 0.91

Table 66: Envigo. Study2A. Acceptance criteria: Induction factor, Z-factor.

Induction factor Z factorrun ID plate 1 plate 2 plate 3 plate 4 plate 5 plate 1 plate 2 plate 3 plate 4 plate 5run 1 86.7 66.7 65.7 0.96 0.85 0.86run 2 76.5 63.7 70.6 0.87 0.54 0.79run 3 61.4 52.6 55.2 0.82 0.8 0.74run 4 61.4 55.9 55 52.6 0.82 0.71 0.82 0.8run 5 68 67.7 0.69 0.65run 6 91.2 82.5 0.61 0.45run 7 74.6 57.9 69.1 0.9 0.75 0.77run 8 74.6 57.9 0.9 0.75run 9 82.5 82.6 90.2 67.1 0.89 0.91 0.76 0.72run 10 100.5 0.93

Table 67: Envigo. Study2B. Acceptance criteria: Induction factor, Z-factor.

Induction factor Z factorrun ID plate 1 plate 2 plate 3 plate 4 plate 5 plate 6 plate 1 plate 2 plate 3 plate 4 plate 5 plate 6run 1 32.3 22.4 24.5 22.8 25.4 27 0.9 0.92 0.84 0.9 0.87 0.8run 2 66.6 69.3 71.6 96.5 0.89 0.93 0.88 0.82run 3 66.6 72.4 69.9 0.89 0.96 0.85run 4 72.5 72.2 0.9 0.82run 5 72.5 75.4 78.8 64.3 0.9 0.92 0.85 0.85run 6 59.4 48.7 57.4 0.88 0.9 0.82run 7 59.4 53.1 56.3 52.7 57.4 0.88 0.82 0.72 0.77 0.82run 8 53.8 54.3 59.5 0.75 0.92 0.89

Table 68: RISE. Study2. Acceptance criteria: Induction factor, Z-factor.

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Induction factor Z factorrun ID plate 1 plate 2 plate 3 plate 4 plate 5 plate 6 plate 1 plate 2 plate 3 plate 4 plate 5 plate 6run 1 103.8 108 118.4 107.8 109.9 100.4 0.85 0.8 0.89 0.87 0.84 0.78run 2 86 93 90.7 92.2 0.81 0.92 0.77 0.9run 3 60.7 63.5 62.8 64.2 67.3 0.95 0.79 0.87 0.87 0.88run 4 63.2 63.6 0.87 0.6run 5 63.2 65 66.1 0.87 0.68 0.87run 6 94.4 97.5 90.4 0.94 0.85 0.87run 7 94.4 98.7 0.94 0.86run 8 71.8 81.8 65.2 74.4 0.91 0.8 0.79 0.79run 9 71.8 80.6 73.9 0.91 0.7 0.85run 10 85.1 83.5 75.8 82.1 0.86 0.8 0.8 0.78run 11 85.1 76.1 80.1 0.86 0.9 0.89run 12 87 90 95.8 0.82 0.92 0.82run 13 68.2 61.3 0.74 0.85run 14 68.2 62.7 63.9 61.9 65.4 0.74 0.81 0.82 0.88 0.82run 15 47.6 49 46.2 46.1 0.86 0.88 0.84 0.8run 16 47.6 46.1 45.3 61.4 0.86 0.8 0.78 0.82run 17 65.7 68.1 0.82 0.87run 18 65.7 69.8 75.6 66.9 75.2 0.82 0.87 0.77 0.78 0.8run 19 92 86.8 88.2 90.7 88.6 0.88 0.88 0.82 0.86 0.88run 20 92 96.7 0.88 0.87run 21 99.8 83.3 71.4 80.3 70.6 0.85 0.89 0.93 0.91 0.89run 22 99.8 70.6 83 0.85 0.89 0.89run 23 81.9 65.5 67.2 66.2 0.95 0.86 0.83 0.82run 24 81.9 0.95run 25 68.1 59.8 56.7 0.93 0.78 0.8run 26 68.1 0.93run 27 76.4 0.92

Table 69: RISE. Study3. Acceptance criteria: Induction factor, Z-factor.

Induction factor Z factorrun ID plate 1 plate 2 plate 3 plate 4 plate 5 plate 6 plate 1 plate 2 plate 3 plate 4 plate 5 plate 6run 1 85.6 73.3 76 74 82.1 78.6 0.59 0.81 0.89 0.88 0.92 0.79run 2 88.5 77.9 82.5 84.8 86.5 0.85 0.83 0.93 0.92 0.87run 3 83.9 87.5 77.7 83.7 76 73.1 0.62 0.79 0.82 0.89 0.87 0.84run 4 78.9 84.9 0.9 0.91run 5 114.1 103.2 102.8 105.6 111.5 115 0.92 0.89 0.9 0.88 0.9 0.88run 6 76.6 104.5 0.97 0.9run 7 71 57.4 56.9 54.2 0.95 0.85 0.88 0.89run 8 82.6 77.3 76 80.8 0.77 0.81 0.87 0.93run 9 68.7 0.92run 10 91.2 98 94.9 0.69 0.83 0.88

Table 70: BDS. Study2. Acceptance criteria: Induction factor, Z-factor.

61

run ID EC50 log10(EC50) CV(EC50) [%] PC NCrun 1 3.37e-010 -9.47 0.34 79.1 0.2run 2 3.38e-010 -9.47 0.16 77.7 0.3run 3 3.74e-010 -9.43 0.27 79.1 40.2run 4 3.29e-010 -9.48 0.35 72.9 0.2run 5 2.86e-010 -9.54 0.22 84.8 0.4run 6 2.86e-010 -9.54 0.22 84.8 0.4run 7 3.52e-010 -9.45 0.18 85.1 12.1run 8 2.44e-010 -9.61 0.24 78.8 0.1run 9 3.76e-010 -9.42 0.36 78.2 28.6run 10 3.76e-010 -9.42 0.36 78.2 28.6run 11 4.54e-010 -9.34 0.24 78.3 0.7run 12 3.31e-010 -9.48 0.24 73.4 0.2run 13 2.97e-010 -9.53 0.27 77.6 6.7run 14 2.97e-010 -9.53 0.27 77.6 6.7run 15 2.87e-010 -9.54 0.3 77 2.5run 16 5.41e-010 -9.27 1.29 84.1 0.3run 17 2.83e-010 -9.55 0.68 73.2 0.1run 18 2.83e-010 -9.55 0.68 73.2 0.1run 19 4.99e-010 -9.3 1.07 74 0.5- - - - - -

average 3.38e-010 -9.46 0.41 78.3 6.8CV [%] 0.96 5.14min 2.44e-010 -9.61 0.16 72.9 0.1max 5.41e-010 -9.27 1.29 85.1 40.2

Table 71: Citoxlab. Study2. Acceptance criteria: EC50 [M], log10(EC50), CV(EC50) [%], PC, NC.

run ID EC50 log10(EC50) CV(EC50) [%] PC NCrun 1 2.02e-010 -9.69 0.24 88.5 0.2run 2 2.29e-010 -9.64 0.89 66.2 -0.8run 3 2.29e-010 -9.64 0.89 66.2 -0.8run 4 3.23e-010 -9.49 0.56 79.2 1run 5 3.23e-010 -9.49 0.56 79.2 1run 6 4.2e-010 -9.38 0.45 66.3 0.2run 7 4.2e-010 -9.38 0.45 66.3 0.2- - - - - -

average 2.95e-010 -9.51 0.57 73.2 0.1CV [%] 1.37 12.49min 2.02e-010 -9.69 0.24 66.2 -0.8max 4.2e-010 -9.38 0.89 88.5 1

Table 72: Envigo. Study2A. Acceptance criteria: EC50 [M], log10(EC50), CV(EC50) [%], PC, NC.

run ID EC50 log10(EC50) CV(EC50) [%] PC NCrun 1 3.23e-010 -9.49 0.58 81.9 8.9run 2 3.46e-010 -9.46 0.45 88.2 0.3run 3 3.53e-010 -9.45 0.64 75.5 0run 4 3.53e-010 -9.45 0.64 75.5 0run 5 4.79e-010 -9.32 0.55 73.7 0.4run 6 2.46e-010 -9.61 0.84 81 0.5run 7 1.05e-010 -9.98 0.79 69.6 0.2run 8 1.05e-010 -9.98 0.79 69.6 0.2run 9 4.17e-010 -9.38 0.43 73.6 0.2run 10 4.38e-010 -9.36 0.53 78.4 0.2- - - - - -

average 2.83e-010 -9.5 0.62 76.7 1.1CV [%] 2.54 7.55min 1.05e-010 -9.98 0.43 69.6 0max 4.79e-010 -9.32 0.84 88.2 8.9

Table 73: Envigo. Study2B. Acceptance criteria: EC50 [M], log10(EC50), CV(EC50) [%], PC, NC.

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run ID EC50 log10(EC50) CV(EC50) [%] PC NCrun 1 2.48e-010 -9.61 0.27 75.8 -1.6run 2 2.62e-010 -9.58 0.29 78.4 -0.1run 3 2.62e-010 -9.58 0.29 78.4 -0.1run 4 2.25e-010 -9.65 0.32 85.1 0.2run 5 2.25e-010 -9.65 0.32 85.1 0.2run 6 2.24e-010 -9.65 0.57 74.7 0.3run 7 2.24e-010 -9.65 0.57 74.7 0.3run 8 1.58e-010 -9.8 0.41 83.9 1.5- - - - - -

average 2.26e-010 -9.64 0.38 79.5 0.1CV [%] 0.72 5.69min 1.58e-010 -9.8 0.27 74.7 -1.6max 2.62e-010 -9.58 0.57 85.1 1.5

Table 74: RISE. Study2. Acceptance criteria: EC50 [M], log10(EC50), CV(EC50) [%], PC, NC.

run ID EC50 log10(EC50) CV(EC50) [%] PC NCrun 1 2.71e-010 -9.57 0.28 84.9 0.2run 2 2.47e-010 -9.61 0.3 82.9 0.1run 3 2.63e-010 -9.58 0.29 83.3 0.1run 4 2.48e-010 -9.61 0.31 77.8 0.1run 5 2.48e-010 -9.61 0.31 77.8 0.1run 6 2.64e-010 -9.58 0.29 75.5 0.2run 7 2.64e-010 -9.58 0.29 75.5 0.2run 8 2.11e-010 -9.68 0.2 81.3 0.1run 9 2.11e-010 -9.68 0.2 81.3 0.1run 10 2.83e-010 -9.55 0.24 76.8 0.2run 11 2.83e-010 -9.55 0.24 76.8 0.2run 12 2.81e-010 -9.55 0.25 80 0.2run 13 2.86e-010 -9.54 0.41 76.8 -0.1run 14 2.86e-010 -9.54 0.41 76.8 -0.1run 15 2.89e-010 -9.54 0.31 74.1 -0.8run 16 2.89e-010 -9.54 0.31 74.1 -0.8run 17 3.83e-010 -9.42 0.29 81.1 0run 18 3.83e-010 -9.42 0.29 81.1 0run 19 3.36e-010 -9.47 0.48 76.7 2run 20 3.36e-010 -9.47 0.48 76.7 2run 21 3.43e-010 -9.47 0.28 75.5 0.4run 22 3.43e-010 -9.47 0.28 75.5 0.4run 23 2.54e-010 -9.59 0.28 75.4 0run 24 2.54e-010 -9.59 0.28 75.4 0run 25 3.31e-010 -9.48 0.18 77 -0.3run 26 3.31e-010 -9.48 0.18 77 -0.3run 27 3.38e-010 -9.47 0.29 79.7 0- - - - - -

average 2.87e-010 -9.54 0.3 78 0.2CV [%] 0.72 3.79min 2.11e-010 -9.68 0.18 74.1 -0.8max 3.83e-010 -9.42 0.48 84.9 2

Table 75: RISE. Study3. Acceptance criteria: EC50 [M], log10(EC50), CV(EC50) [%], PC, NC.

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run ID EC50 log10(EC50) CV(EC50) [%] PC NCrun 1 3.09e-010 -9.51 0.86 67.1 0.2run 2 3.2e-010 -9.5 0.45 68.2 0.1run 3 4.18e-010 -9.38 0.5 79.8 -0.1run 4 3.47e-010 -9.46 0.18 80.8 -0.1run 5 3.94e-010 -9.4 0.26 80.3 0.2run 6 4.36e-010 -9.36 0.26 83.1 -0.1run 7 3.43e-010 -9.47 0.26 76 0.4run 8 2.63e-010 -9.58 0.38 83.8 0.5run 9 4.8e-010 -9.32 0.47 80.2 0.6run 10 2.58e-010 -9.59 0.63 72.2 0.2- - - - - -

average 3.5e-010 -9.45 0.42 77.1 0.2CV [%] 0.96 7.81min 2.58e-010 -9.59 0.18 67.1 -0.1max 4.8e-010 -9.32 0.86 83.8 0.6

Table 76: BDS. Study2. Acceptance criteria: EC50 [M], log10(EC50), CV(EC50) [%], PC, NC.

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B.2 Antagonist testing

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Figure 30: Citoxlab,Study2 Flutamide responses.

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Figure 31: Envigo,Study2A Flutamide responses.

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Rela

tive Induction [%

]

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Rela

tive Induction [%

]

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log10(M)

Rela

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]

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Rela

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Rela

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]

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Rela

tive Induction [%

]

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log10(M)

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tive Induction [%

]

Figure 32: Envigo,Study2B Flutamide responses.

66

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log10(M)

Rela

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]

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tive Induction [%

]

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Rela

tive Induction [%

]

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Rela

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]

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log10(M)

Rela

tive Induction [%

]

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log10(M)

Rela

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Figure 33: RISE,Study2 Flutamide responses.

67

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Rela

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Rela

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Rela

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Rela

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Figure 34: RISE,Study3 Flutamide responses.68

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Figure 35: BDS,Study2 Flutamide responses.

69

Inhibition factor Z factorrun ID plate 1 plate 2 plate 3 plate 4 plate 1 plate 2 plate 3 plate 4run 1 7.5 22.9 42.8 0.58 0.66 0.74run 2 14.6 35.3 48.3 0.56 0.86 0.79run 3 32.8 55.6 48.3 0.92 0.79 0.9run 4 66.2 43.5 40 52.7 0.89 0.79 0.83 0.83run 5 66.1 41.9 53.8 61.6 0.85 0.81 0.83 0.78run 6 89.5 45.1 52.4 50 0.86 0.87 0.87 0.73run 7 76.9 57.1 50.1 0.8 0.69 0.79run 8 58.3 52.3 0.86 0.78run 9 43.9 44.1 37.9 42.2 0.98 0.86 0.82 0.92run 10 50.6 44.3 50.8 46.9 0.69 0.85 0.83 0.93run 11 51.4 35.2 43.3 49.1 0.85 0.86 0.87 0.76run 12 59.8 65 58.1 0.82 0.79 0.93run 13 72.7 54.6 45 0.93 0.69 0.32run 14 62.5 61.2 63.1 0.51 0.73 0.82run 15 13.7 11.9 14.1 0.64 0.77 0.85run 16 73.3 60.1 52.3 39.6 0.94 0.8 0.79 0.82run 17 49.4 58.6 52.8 0.95 0.75 0.86run 18 63.2 58.6 64.4 52.8 0.81 0.76 0.8 0.68run 19 72.3 52.6 54.3 0.69 0.79 0.92run 20 69.4 61.2 60.5 56 0.81 0.72 0.89 0.81run 21 66.2 60 61.1 65 0.93 0.86 0.85 0.89run 22 63 56.2 50.3 0.83 0.73 0.81

Table 77: Citoxlab. Study2. Antagonist testing. Acceptance criteria: Inhibition factor, Z-factor.

Inhibition factor Z factorrun ID plate 1 plate 2 plate 3 plate 4 plate 5 plate 6 plate 1 plate 2 plate 3 plate 4 plate 5 plate 6run 1 28.9 24.7 30.3 37.1 30.5 31 0.7 0.6 0.7 0.74 0.71 0.8run 2 36.8 29.1 37.3 28.1 0.81 0.77 0.87 0.71run 3 14.1 15.2 13.6 16 0.76 0.35 0.43 0.66run 4 32.1 31.9 34 32.3 0.9 0.75 0.67 0.74run 5 23.3 28.9 28 31 31.1 24.8 0.65 0.68 0.68 0.75 0.56 -0.09run 6 29.1 28.7 34.8 28.9 32.4 23.8 0.88 0.72 0.81 0.73 0.59 0.65run 7 21.5 22.7 24.5 23.7 29.4 26.7 0.52 0.57 0.71 0.44 0.45 0.48

Table 78: Envigo. Study2A. Antagonist testing. Acceptance criteria: Inhibition factor, Z-factor.

Inhibition factor Z factorrun ID plate 1 plate 2 plate 3 plate 4 plate 5 plate 6 plate 1 plate 2 plate 3 plate 4 plate 5 plate 6run 1 31.4 30.6 33.2 41.6 32.2 0.78 0.8 0.75 0.81 0.09run 2 30.7 33.3 34.3 0.79 0.76 0.76run 3 31.5 39 35.4 0.59 0.75 0.74run 4 28.1 22.1 0.75 0.81run 5 28.1 25 31.3 27.4 0.75 0.78 0.71 0.77run 6 34.8 44.7 48.9 40.9 31 38.6 0.85 0.86 0.82 0.65 0.3 0.69run 7 41.2 40.3 38.9 39.8 34.7 37.8 0.71 0.64 0.58 0.84 0.46 0.58run 8 47 54.7 0.96 0.84run 9 47 41.4 48.2 0.96 0.84 0.7run 10 11.9 17.7 18.9 0.8 0.9 0.82run 11 31.7 34.5 0.82 0.77

Table 79: Envigo. Study2B. Antagonist testing. Acceptance criteria: Inhibition factor, Z-factor.

70

Inhibition factor Z factorrun ID plate 1 plate 2 plate 3 plate 4 plate 5 plate 6 plate 1 plate 2 plate 3 plate 4 plate 5 plate 6run 1 37 34.7 37.6 35.5 33.9 29.9 0.94 0.87 0.84 0.74 0.79 0.75run 2 40 34 0.83 0.77run 3 40 35.1 33.8 37.7 36.9 0.83 0.84 0.88 0.89 0.7run 4 30.6 33.2 31.8 0.91 0.82 0.9run 5 30.6 27.3 33.3 0.91 0.86 0.91run 6 39.8 35.1 38.5 0.85 0.94 0.77run 7 30.1 32.1 0.69 0.64run 8 30.1 33.7 30.6 34.1 31.7 0.69 0.55 0.85 0.85 0.73run 9 32.9 29.4 0.85 0.84run 10 32.9 27.1 0.85 0.82run 11 25 32.7 28.1 27.5 29.4 26.6 0.89 0.8 0.8 0.85 0.8 0.85

Table 80: RISE. Study2. Antagonist testing. Acceptance criteria: Inhibition factor, Z-factor.

Inhibition factor Z factorrun ID plate 1 plate 2 plate 3 plate 4 plate 5 plate 6 plate 1 plate 2 plate 3 plate 4 plate 5 plate 6run 1 43.8 35.5 38.6 38.6 35.4 35.1 0.91 0.85 0.85 0.79 0.81 0.91run 2 40.6 45 43.8 0.86 0.9 0.83run 3 40.6 43 39.8 0.86 0.8 0.76run 4 27.4 31 34.5 0.9 0.89 0.78run 5 27.4 33.2 36.9 33.1 0.9 0.87 0.78 0.79run 6 34.8 33.3 34.1 0.92 0.92 0.6run 7 34.8 34.9 34.5 37.7 0.92 0.76 0.76 0.78run 8 44.3 40.8 39.9 0.85 0.89 0.83run 9 44.3 37.4 46.1 42.3 0.85 0.84 0.85 0.79run 10 35.5 32.3 28.6 31.1 30.3 36.6 0.76 0.69 0.76 0.84 0.7 0.84run 11 41 35.8 39.5 33.6 0.7 0.78 0.8 0.71run 12 42.4 41 44 33.3 42.6 37.1 0.41 0.86 0.82 0.86 0.84 0.88run 13 33.5 33.2 31.3 29.8 27.4 33.4 0.57 0.61 0.77 0.73 0.55 0.79run 14 30.7 24.4 25 26.4 28.5 0.34 0.53 0.75 0.75 0.58run 15 30 26.6 32 30.6 11.7 0.84 0.8 0.83 0.64 0.25run 16 40.6 28.7 30.8 35.4 25.3 28.6 0.71 0.73 0.72 0.87 0.66 0.8run 17 32.9 26 30.9 30.9 31.9 27.7 0.41 0.46 0.57 0.56 0.59 0.65run 18 22.5 24.6 27 23.5 0.41 0.74 0.7 0.74run 19 22.5 25.9 24.6 0.41 0.69 0.7run 20 42 38.5 42.8 42.3 41 38.4 0.78 0.81 0.89 0.89 0.88 0.84run 21 39 44.5 44 40.4 39.6 38.2 0.91 0.81 0.86 0.8 0.8 0.76run 22 30.9 29.3 34.5 29.1 27.8 0.83 0.85 0.86 0.88 0.79run 23 30.9 34.6 0.83 0.89run 24 41.7 32.6 38.7 32.7 32.2 33.7 0.83 0.87 0.83 0.87 0.72 0.89run 25 38.7 37.3 32.9 38.3 39 27.3 0.85 0.77 0.86 0.89 0.86 0.74run 26 33.7 40 0.95 0.84run 27 36.9 32.8 41.3 39.2 44.3 41 0.75 -0.58 0.76 0.85 0.82 0.8run 28 37 33.1 31.2 35.4 35 38.4 0.79 0.85 0.91 0.89 0.87 0.83run 29 39.5 28.5 35.6 0.92 0.72 0.82run 30 33.5 33.2 34.6 37.7 35.6 34.2 0.81 0.84 0.79 0.86 0.83 0.86run 31 28 21.3 21.4 28.2 26.7 26.6 0.77 0.8 0.7 0.84 0.81 0.83run 32 32 29.7 28.7 0.78 0.74 0.78run 33 32 29 0.78 0.71run 34 26.8 24.6 23.7 27.1 27 31.5 0.88 0.68 0.68 0.83 0.69 0.85

Table 81: RISE. Study3. Antagonist testing. Acceptance criteria: Inhibition factor, Z-factor.

71

Inhibition factor Z factorrun ID plate 1 plate 2 plate 3 plate 4 plate 5 plate 6 plate 1 plate 2 plate 3 plate 4 plate 5 plate 6run 1 30.8 34.8 30.9 31.1 34.3 30.7 0.83 0.7 0.8 0.74 0.76 0.67run 2 33.8 33.1 32.5 32.3 31.1 0.84 0.77 0.87 0.92 0.84run 3 35 38.7 32.8 33.9 33.8 35.3 0.77 0.87 0.84 0.84 0.89 0.85run 4 28.6 26.3 24.9 24.1 25.6 26.2 0.9 0.79 0.94 0.77 0.82 0.85run 5 33.2 26.6 32.6 37.5 35.6 32.1 0.57 0.66 0.87 0.88 0.92 0.86run 6 31.7 28.4 29 1 29.8 27.9 0.88 0.77 0.82 -71.23 0.88 0.86run 7 29.3 28.8 25.7 28.5 26.8 25.1 0.9 0.85 0.9 0.82 0.69 0.78run 8 23 28.2 25.1 25.9 24.7 23.1 0.65 0.68 0.68 0.58 0.92 0.71run 9 28.6 27.4 27.1 27.9 28.3 27.5 0.92 0.88 0.83 0.92 0.85 0.94run 10 28.8 26.6 27.4 26.6 27.9 29.1 0.87 0.89 0.94 0.88 0.86 0.81run 11 32.1 35 33.9 34.2 31.9 0.9 0.81 0.94 0.89 0.87run 12 29.4 35.2 33.2 30.3 32.7 34.3 0.82 0.91 0.67 0.83 0.79 0.9run 13 31 33 0.95 0.72run 14 26.3 28.4 21.9 0.84 0.78 0.7run 15 26.3 23.6 27.5 0.84 0.69 0.62run 16 28 30.1 30.1 0.73 0.81 0.59run 17 33.6 37.6 0.7 0.82

Table 82: BDS. Study2. Antagonist testing. Acceptance criteria: Inhibition factor, Z-factor.

run ID IC50 log10(IC50) CV(IC50) [%] PC NC VC R2

run 1 3.23e-007 -6.49 0.64 0.2 353.1 -10.1run 2 4.43e-007 -6.35 0.57 7.3 171.8 -0.4run 3 3.9e-007 -6.41 0.55 11 275.5 -0.4run 4 3.92e-007 -6.41 0.66 10.3 169 0.3run 5 5.09e-007 -6.29 0.41 13.4 166 0.8run 6 5.19e-007 -6.28 0.37 10.6 123.4 0.2 0.35run 7 6.12e-007 -6.21 0.59 15.4 144.6 1.2 0.49run 8 6.74e-007 -6.17 0.44 14.8 160.3 0.1 0.49run 9 5.4e-007 -6.27 0.52 12.2 150.4 0.7 0.48run 10 4.61e-007 -6.34 0.61 10.1 147.9 0.6 0.46run 11 3.08e-007 -6.51 0.2 12.5 151.6 0.5 0.43run 12 5.87e-007 -6.23 0.55 20.3 155.4 1.1run 13 5.5e-007 -6.26 0.76 9.2 119.4 0.1run 14 3.11e-007 -6.51 1.88 13.9 112.7 37.9run 15 3.41e-007 -6.47 0.91 13.9 613.7 3.5run 16 5.97e-007 -6.22 0.46 11.3 133.4 0.5 0.45run 17 6.49e-007 -6.19 0.69 15.5 129.3 -0.1 0.59run 18 9.86e-007 -6.01 0.11 13 128.2 73.6 0.32run 19 5.45e-007 -6.26 0.81 12.1 115.4 0.4 0.38run 20 4.91e-007 -6.31 0.6 11.5 122.9 12.6 0.4run 21 4.52e-007 -6.34 0.56 8.9 118.8 0.3 0.46run 22 5.73e-007 -6.24 0.59 14.3 137.8 1.1 0.56- - - - - - - -

average 4.92e-007 -6.29 0.61 11.89 177.31 5.65 0.45CV [%] 1.97 31.94 63.26min 3.08e-007 -6.51 0.11 0.2 112.7 -10.1 0.32max 9.86e-007 -6.01 1.88 20.3 613.7 73.6 0.59

Table 83: Citoxlab. Study2. Antagonist testing. Acceptance criteria: IC50 [M], log10(IC50),CV(IC50) [%], PC, NC, VC, R2

72


run 1 6.31e-007 -6.2 0.62 11.7 119 2run 2 4.78e-007 -6.32 0.63 9.7 115.6 -0.2run 3 2.68e-007 -6.57 2.52 3.6 89.6 75run 4 8.29e-007 -6.08 0.93 5.8 135.9 -0.3run 5 5.36e-007 -6.27 1.29 10.9 115.4 -0.5 0.2run 6 3.49e-007 -6.46 0.81 10.2 116.2 1 0.63run 7 6.74e-007 -6.17 1.3 11.8 97.4 -0.9 0.45- - - - - - - -

average 5.06e-007 -6.27 1.16 9.09 112.73 10.89 0.43CV [%] 2.72 34.59 13.42min 2.68e-007 -6.57 0.62 3.6 89.6 -0.9 0.2max 8.29e-007 -6.08 2.52 11.8 135.9 75 0.63

Table 84: Envigo. Study2A. Antagonist testing. Acceptance criteria: IC50 [M], log10(IC50),CV(IC50) [%], PC, NC, VC, R2


run 1 5.22e-007 -6.28 0.71 8.4 143.7 1run 2 6.25e-007 -6.2 0.73 12.9 132.7 0.1run 3 6.5e-007 -6.19 0.8 10.9 134.8 -0.2run 4 5.65e-007 -6.25 1.97 11.5 148.6 0.8run 5 5.65e-007 -6.25 1.97 11.5 148.6 0.8run 6 4.39e-007 -6.36 0.6 27.8 99.1 0.6 0.43run 7 8.08e-007 -6.09 0.55 12.4 125.6 10.2 0.42run 8 8.01e-007 -6.1 1.06 23.8 161 0.2 NaNrun 9 8.01e-007 -6.1 1.06 23.8 161 0.2 0.36run 10 6.17e-007 -6.21 0.64 19 141.2 1.4 0.33run 11 8.23e-007 -6.08 1.08 18.7 101.3 0.5 0.5- - - - - - - -

average 6.43e-007 -6.18 1.02 16.44 136.14 1.42 0.41CV [%] 1.47 39.55 15.3min 4.39e-007 -6.36 0.55 8.4 99.1 -0.2 0.33max 8.23e-007 -6.08 1.97 27.8 161 10.2 0.5

Table 85: Envigo. Study2B. Antagonist testing. Acceptance criteria: IC50 [M], log10(IC50),CV(IC50) [%], PC, NC, VC, R2


run 1 4.2e-007 -6.38 0.45 10.5 121.3 6.5run 2 5.02e-007 -6.3 0.53 11.5 134.2 0.3run 3 5.02e-007 -6.3 0.53 11.5 134.2 0.3 0.51run 4 5.9e-007 -6.23 0.63 11.5 132.9 0run 5 5.9e-007 -6.23 0.63 11.5 132.9 0 0.5run 6 5.42e-007 -6.27 0.45 13.4 120.3 -0.1 0.5run 7 5.03e-007 -6.3 0.73 14.7 127 1.1run 8 5.03e-007 -6.3 0.73 14.7 127 1.1 0.5run 9 4.82e-007 -6.32 0.53 13.8 130.1 0.4run 10 4.82e-007 -6.32 0.53 13.8 130.1 0.4 0.45run 11 5.39e-007 -6.27 0.58 15.8 149.7 0 0.51- - - - - - - -

average 5.12e-007 -6.29 0.57 12.98 130.89 0.89 0.49CV [%] 0.67 13.26 6.03min 4.2e-007 -6.38 0.45 10.5 120.3 -0.1 0.45max 5.9e-007 -6.23 0.73 15.8 149.7 6.5 0.51

Table 86: RISE. Study2. Antagonist testing. Acceptance criteria: IC50 [M], log10(IC50), CV(IC50)[%], PC, NC, VC, R2

73


run 1 4.39e-007 -6.36 0.43 14 132.3 0.1run 2 4.02e-007 -6.4 0.41 14.8 133.5 -0.2 0.51run 3 4.02e-007 -6.4 0.41 14.8 133.5 -0.2run 4 4.18e-007 -6.38 0.55 13.5 152.9 -0.5 0.27run 5 4.18e-007 -6.38 0.55 13.5 152.9 -0.5run 6 4.94e-007 -6.31 0.56 8.6 125 0.1 0.58run 7 4.94e-007 -6.31 0.56 8.6 125 0.1run 8 5.74e-007 -6.24 0.36 14.2 143.6 -0.2 NaNrun 9 5.74e-007 -6.24 0.36 14.2 143.6 -0.2run 10 4.63e-007 -6.33 1.22 14.2 153.2 0.1 NaNrun 11 3.72e-007 -6.43 0.87 10.9 132 0.3run 12 3.83e-007 -6.42 0.94 10.2 125.1 0.1 0.45run 13 4.14e-007 -6.38 0.91 12.1 129.3 -0.1 0.46run 14 4.67e-007 -6.33 1.02 11 132.3 0.1 0.38run 15 3.94e-007 -6.4 0.82 10.4 142.7 0.5run 16 4.1e-007 -6.39 0.9 11.1 166.6 1.3 0.42run 17 3.62e-007 -6.44 1.82 14.9 150 -0.1 NaNrun 18 2.54e-007 -6.6 2.32 11.1 136 -0.2run 19 2.54e-007 -6.6 2.32 11.1 136 -0.2 0.37run 20 4.8e-007 -6.32 0.44 14.2 131.4 0 0.49run 21 5.51e-007 -6.26 0.39 12.8 128.4 -0.2run 22 4.17e-007 -6.38 0.34 9.4 126.7 -0.2 0.45run 23 4.17e-007 -6.38 0.34 9.4 126.7 -0.2run 24 4.67e-007 -6.33 0.37 11.9 134.2 0.2 0.41run 25 5.49e-007 -6.26 0.38 17.4 132.9 0.3 0.46run 26 4.89e-007 -6.31 0.39 16.2 153.5 -0.2run 27 4.49e-007 -6.35 0.61 18.7 143.9 -0.1 0.43run 28 3.88e-007 -6.41 0.69 23.8 165.8 0.8 0.47run 29 4.18e-007 -6.38 0.55 15.4 153.4 -0.1run 30 4.24e-007 -6.37 0.71 21.7 165.1 0.2 0.51run 31 4.36e-007 -6.36 0.43 11.4 199.2 -0.1 0.51run 32 4.39e-007 -6.36 0.56 10 184.7 0.4run 33 4.39e-007 -6.36 0.56 10 184.7 0.4 0.49run 34 5.7e-007 -6.24 0.41 11.2 205 0.4 0.42- - - - - - - -

average 4.32e-007 -6.36 0.72 13.15 146.51 0.05 0.45CV [%] 1.26 26.53 14.57min 2.54e-007 -6.6 0.34 8.6 125 -0.5 0.27max 5.74e-007 -6.24 2.32 23.8 205 1.3 0.58

Table 87: RISE. Study3. Antagonist testing. Acceptance criteria: IC50 [M], log10(IC50), CV(IC50)[%], PC, NC, VC, R2


run 1 4.77e-007 -6.32 0.61 10.5 138.4 -0.2run 2 4.12e-007 -6.38 0.48 11.8 127.2 -0.1run 3 4.83e-007 -6.32 0.61 12 132.8 6.8run 4 5.02e-007 -6.3 0.37 12.6 163 6run 5 3.62e-007 -6.44 0.6 12 164.4 7.5 0.5run 6 3.95e-007 -6.4 0.61 11.8 158.3 NaN 0.56run 7 4.71e-007 -6.33 0.57 13.2 129.1 6.4 0.38run 8 4.49e-007 -6.35 0.71 14.3 130.5 8.5 0.47run 9 4.35e-007 -6.36 0.54 13.7 134.3 5.6 0.44run 10 4.16e-007 -6.38 0.32 13.7 144.4 6.3 0.45run 11 5.71e-007 -6.24 0.43 11.6 119.6 5.7 0.45run 12 5.49e-007 -6.26 0.44 13.9 133.5 7.3 0.38run 13 6.3e-007 -6.2 0.58 13.5 133.6 6.4 0.45run 14 5.32e-007 -6.27 0.88 9 151.9 4.9 0.55run 15 5.32e-007 -6.27 0.88 9 151.9 4.9 0.55run 16 5.57e-007 -6.25 0.7 12.8 135.3 4.7 0.54run 17 6.14e-007 -6.21 0.71 0 127.6 6.2 0.45- - - - - - - -

average 4.88e-007 -6.31 0.59 11.49 139.76 5.44 0.47CV [%] 1.09 29.15 9.63min 3.62e-007 -6.44 0.32 0 119.6 -0.2 0.38max 6.3e-007 -6.2 0.88 14.3 164.4 8.5 0.56

Table 88: BDS. Study2. Antagonist testing. Acceptance criteria: IC50 [M], log10(IC50), CV(IC50)[%], PC, NC, VC, R2

74

Appendix C Responses - Agonist

75

C.1 Test item 1

−11 −10 −9 −8 −7

10

20

30

40

50

60

70

80

90

100

log10(M)

Re

lative

In

du

ctio

n [

%]

TI−CIT2CB, run 5, Citoxlab

−11 −10 −9 −8 −7

10

20

30

40

50

60

70

80

90

100

log10(M)

Re

lative

In

du

ctio

n [

%]


−11 −10 −9 −8 −70

10

20

30

40

50

60

70

80

90

100

log10(M)

Re

lative

In

du

ctio

n [

%]


−11 −10 −9 −8 −7

10

20

30

40

50

60

70

80

90

100

110

log10(M)

Re

lative

In

du

ctio

n [

%]

TI−ENV2VP, run 3, Envigo

−11 −10 −9 −8 −7

10

20

30

40

50

60

70

80

90

100

log10(M)

Re

lative

In

du

ctio

n [

%]


−11 −10 −9 −8 −70

10

20

30

40

50

60

70

80

90

100

log10(M)

Re

lative

In

du

ctio

n [

%]


−11 −10 −9 −8 −7

10

20

30

40

50

60

70

80

90

100

log10(M)

Re

lative

In

du

ctio

n [

%]

TI−8WT, run 3, RISE

−11 −10 −9 −8 −70

10

20

30

40

50

60

70

80

90

100

log10(M)

Re

lative

In

du

ctio

n [

%]


−11 −10 −9 −8 −70

10

20

30

40

50

60

70

80

90

100

log10(M)

Re

lative

In

du

ctio

n [

%]


−11 −10 −9 −8 −7

10

20

30

40

50

60

70

80

90

100

110

log10(M)

Re

lative

In

du

ctio

n [

%]

TI−BDS2SQ, run 7, BDS

−11 −10 −9 −8 −7

10

20

30

40

50

60

70

80

90

100

log10(M)

Re

lative

In

du

ctio

n [

%]


−11 −10 −9 −8 −7

1020

3040

5060

7080

90100

110

log10(M)

Re

lative

In

du

ctio

n [

%]


Figure 36: Test item 1. Relative induction responses for accepted experiments in four participartinglabs. Legend: relative Induction Yc ( ), single replicate for Yc ( ), DHT ( ).

76

−11 −10 −9 −8 −70

10

20

30

40

50

60

70

80

90

100

log10(M)

Rela

tive Induction [%

]

TI−CIT2CB, Citoxlab

run 5

run 8

run 13

DHT

−11 −10 −9 −8 −70

10

20

30

40

50

60

70

80

90

100

110

log10(M)

Rela

tive Induction [%

]

TI−ENV2VP, Envigo

run 3

run 5

run 7

DHT

−11 −10 −9 −8 −7

10

20

30

40

50

60

70

80

90

100

log10(M)

Rela

tive Induction [%

]

TI−8WT, RISE

run 3

run 5

run 7

DHT

−11 −10 −9 −8 −7

10

20

30

40

50

60

70

80

90

100

log10(M)

Rela

tive Induction [%

]

TI−BDS2SQ, BDS

run 7

run 8

run 10

DHT

Figure 37: Test item 1. Relative induction responses for accepted experiments. Aggregated bylaboratory.

−11 −10 −9 −8 −70

10

20

30

40

50

60

70

80

90

100

110

log10(M)

Rela

tive

In

du

ctio

n [

%]


Citoxlab

Envigo

RISE

BDS

DHT

Figure 38: Test item 1. Relative induction responses for accepted experiments. Aggregated bylaboratory and biological replicates.

77

Citoxlab

Envigo

RISE

BDS

run5

run8

run13

run3

run5

run7

run3

run5

run7

run7

run8

run10

[µM]

[mg/ml]

COM

COM

COM

COM

COM

COM

COM

COM

COM

COM

COM

COM

4.99e-6

1.35e-9

0.2(0.2)

0.3(0.3)

0(0.2)

1.66e-5

4.5e-9

24.5(0.9)

0.8(0.1)

0.1(0.1)

3.1(0.7)

1.4(0.4)

1.3(0.2)

1.4(0.2)

8(0.4)

1.5(0.3)

2.1(0.2)

2(0)

1.9(0.2)

4.99e-5

1.35e-8

7.4(1.7)

12(0.7)

11.3(1.7)

5.55e-5

1.5e-8

4.8(0.2)

5.9(1)

8(0.5)

15(1.6)

22(0.6)

8.3(1.1)

11.4(0.4)

11.1(0.4)

13(0.8)

1.66e-4

4.5e-8

22.8(1)

27.8(2)

30.4(1.9)

37.5(1.3)

38.1(2.4)

37.9(1.6)

37.7(1.6)

44.9(1.7)

42.4(1.7)

39.8(3.3)

41.4(0.3)

39.5(2.9)

4.99e-4

1.35e-7

66.6(5.8)

67.4(4.1)

72.6(1.9)

5.55e-4

1.5e-7

55.2(1.8)

57.5(1.8)

63.1(0.9)

74.5(7.6)

74.6(4.3)

68.4(3.2)

76.3(6.2)

74.8(3.3)

79(3.7)

1.66e-3

4.5e-7

74.7(1.5)

79.8(2.4)

75.2(2.4)

91.9(16.3)

98.1(8.5)

79.6(4.9)

85.9(0.4)

87.2(0.6)

82.1(8.5)

94.3(6.7)

93.7(1.5)

91(8.7)

4.99e-3

1.35e-6

89.6(4.1)

89.6(2.3)

87.9(2.6)

5.55e-3

1.5e-6

80(0.9)

85.6(1.7)

83.3(2)

97.8(8.8)

88.7(8.3)

92.4(10.6)

105.2(3)

102.7(2.8)

96.1(13.1)

1.66e-2

4.5e-6

86(1)

90(2.2)

81.1(2.9)

100.2(8)

92.9(15.2)

88.4(3.8)

91.7(3.4)

90.7(4.1)

95.2(7.1)

107(5.6)

104.1(2.5)

102.3(14.9)

5.55e-2

1.5e-5

85.4(2.1)

93.6(5.5)

89.5(2)

99.9(3.9)

92(5.3)

88.9(6.2)

104.8(5.3)

101.4(3.2)

102.4(7.8)

log 1

0(PC10)[mg/ml]

-7.61

-7.71

-7.77

-8-8.19

-7.79

-7.81

-7.93

-7.9

-7.86

-7.85

-7.91

log 1

0(EC50)[mg/ml]

-7.01

-7.02

-7.15

-7.18

-7.29

-7.21

-7.21

-7.29

-7.29

-7.15

-7.18

-7.21

Table 89: Test item 1. Relative induction Yc with sample std in brackets(N=3). Estimatedlog10(EC50) and log10(PC10) values. Highlighted in green values where Yc ≥ 10.

78

C.2 Test item 2

−11 −10 −9 −8 −7

10

20

30

40

50

60

70

80

90

100

log10(M)

Re

lative

In

du

ctio

n [

%]

TI−CIT2XF, run 5, Citoxlab

−11 −10 −9 −8 −7

10

20

30

40

50

60

70

80

90

100

log10(M)

Re

lative

In

du

ctio

n [

%]


−11 −10 −9 −8 −70

10

20

30

40

50

60

70

80

90

100

log10(M)

Re

lative

In

du

ctio

n [

%]


−11 −10 −9 −8 −7

10

20

30

40

50

60

70

80

90

100

110

log10(M)

Re

lative

In

du

ctio

n [

%]

TI−ENV2XN, run 3, Envigo

−11 −10 −9 −8 −7

10

20

30

40

50

60

70

80

90

100

log10(M)

Re

lative

In

du

ctio

n [

%]


−11 −10 −9 −8 −70

10

20

30

40

50

60

70

80

90

100

log10(M)

Re

lative

In

du

ctio

n [

%]


−11 −10 −9 −8 −7

10

20

30

40

50

60

70

80

90

100

log10(M)

Re

lative

In

du

ctio

n [

%]

TI−10NM, run 3, RISE

−11 −10 −9 −8 −7

10

20

30

40

50

60

70

80

90

100

log10(M)

Re

lative

In

du

ctio

n [

%]


−11 −10 −9 −8 −7

10

20

30

40

50

60

70

80

90

100

log10(M)

Re

lative

In

du

ctio

n [

%]


−11 −10 −9 −8 −7

10

20

30

40

50

60

70

80

90

100

log10(M)

Re

lative

In

du

ctio

n [

%]

TI−BDS2GG, run 7, BDS

−11 −10 −9 −8 −7

10

20

30

40

50

60

70

80

90

100

log10(M)

Re

lative

In

du

ctio

n [

%]


−11 −10 −9 −8 −70

10

20

30

40

50

60

70

80

90

100

log10(M)

Re

lative

In

du

ctio

n [

%]



79

−11 −10 −9 −8 −70

10

20

30

40

50

60

70

80

90

100

log10(M)

Rela

tive Induction [%

]

TI−CIT2XF, Citoxlab

run 5

run 8

run 13

DHT

−11 −10 −9 −8 −70

10

20

30

40

50

60

70

80

90

100

110

log10(M)

Rela

tive Induction [%

]

TI−ENV2XN, Envigo

run 3

run 5

run 7

DHT

−11 −10 −9 −8 −7

10

20

30

40

50

60

70

80

90

100

log10(M)

Rela

tive Induction [%

]

TI−10NM, RISE

run 3

run 5

run 7

DHT

−11 −10 −9 −8 −70

10

20

30

40

50

60

70

80

90

100

log10(M)

Rela

tive Induction [%

]

TI−BDS2GG, BDS

run 7

run 8

run 9

DHT


−11 −10 −9 −8 −70

10

20

30

40

50

60

70

80

90

100

110

log10(M)

Rela

tive

In

du

ctio

n [

%]


Citoxlab

Envigo

RISE

BDS

DHT


80

Citoxlab

Envigo

RISE

BDS

run5

run8

run13

run3

run5

run7

run3

run5

run7

run7

run8

run9

[µM]

[mg/ml]

COM

COM

COM

COM

COM

COM

COM

COM

COM

COM

COM

COM

1.37e-5

4.5e-9

0.6(0.2)

0.3(0.1)

0.3(0)

0.1(0.1)

0.2(0.1)

0(0.1)

4.11e-5

1.35e-8

0.4(0.1)

0.6(0.1)

4.57e-5

1.5e-8

2.6(0.5)

0.7(0.1)

0.6(0.2)

0.3(0.1)

0.6(0)

0.4(0)

1.37e-4

4.5e-8

1.7(0)

0.8(0.1)

0.5(0.1)

7(0.6)

3.2(0.6)

1.9(0.2)

1.4(0.2)

2.6(0.3)

2.4(0.2)

1.8(0.1)

2.5(0.1)

2.4(0.2)

4.11e-4

1.35e-7

11.3(1.1)

7.9(0.3)

4.57e-4

1.5e-7

8(0.1)

7.7(0.3)

6.1(0.3)

20.6(2)

14.3(2.8)

13(1.3)

9.1(0.5)

8.4(0.3)

12.8(0.4)

12.7(0.9)

1.37e-3

4.5e-7

25.4(1.4)

27.3(0.6)

24.9(1.5)

55.6(7.7)

31.3(6.1)

35.2(0.9)

33(3.2)

37.8(1.6)

35.4(1.3)

27.8(1.7)

37.1(0.8)

31.1(2.9)

4.11e-3

1.35e-6

57.7(1.5)

54.1(2.8)

4.57e-3

1.5e-6

54.3(2.1)

62.2(2.4)

50.3(1.6)

80.8(8.7)

79.2(8)

63.7(2.7)

57.1(3.6)

52.6(6.2)

61(2.9)

52.3(3.7)

1.37e-2

4.5e-6

66.8(2.4)

64.3(3)

66(0.1)

90(9.7)

83.5(12.1)

78.9(6.3)

67.2(1.3)

74.6(1.1)

67.8(3.6)

66.1(3.5)

73.3(1.2)

60.9(3.7)

4.11e-2

1.35e-5

75.5(1.8)

72.8(1)

4.57e-2

1.5e-5

76.3(4.4)

69(1.2)

69(3.6)

92.8(7.3)

83.2(9.5)

86(5.7)

73.5(3.2)

70.3(6.6)

74.5(6.2)

66(4.1)

1.37e-1

4.5e-5

75.2(2.2)

69.5(2)

71.8(1.3)

75.3(3.9)

76.9(1.4)

76.4(6)

4.57e-1

1.5e-4

78.6(3.2)

70.9(2.2)

77.6(3.4)

74.1(1.2)

log 1

0(PC10)[mg/ml]

-6.74

-6.73

-6.7

-7.13

-7.01

-6.92

-6.8

-6.91

-6.82

-6.77

-6.9

-6.92

log 1

0(EC50)[mg/ml]

-6.1

-6.27

-6.09

-6.46

-6.27

-6.19

-6.24

-6.3

-6.25

-6.18

-6.32

-6.3


81

C.3 Test item 3

−11 −10 −9 −8 −7 −6 −5 −40

10

20

30

40

50

60

70

80

90

100

log10(M)

Re

lative

In

du

ctio

n [

%]

TI−CIT2AE, run 2, Citoxlab

−11 −10 −9 −8 −7 −6 −5 −40

10

20

30

40

50

60

70

80

90

100

log10(M)

Re

lative

In

du

ctio

n [

%]


−11 −10 −9 −8 −7 −6 −50

10

20

30

40

50

60

70

80

90

100

log10(M)

Re

lative

In

du

ctio

n [

%]


−11 −10 −9 −8 −7 −6 −5 −40

10

20

30

40

50

60

70

80

90

100

log10(M)

Re

lative

In

du

ctio

n [

%]

TI−ENV2HD, run 1, Envigo

−11 −10 −9 −8 −7 −6 −5 −40

10

20

30

40

50

60

70

80

90

100

110

log10(M)

Re

lative

In

du

ctio

n [

%]


−11 −10 −9 −8 −7 −6 −5

10

20

30

40

50

60

70

80

90

100

log10(M)

Rela

tive Induction [%

]


−11 −10 −9 −8 −7 −6 −50

10

20

30

40

50

60

70

80

90

100

log10(M)

Re

lative

In

du

ctio

n [

%]

TI−3HX, run 3, RISE

−11 −10 −9 −8 −7 −6 −50

10

20

30

40

50

60

70

80

90

100

log10(M)

Re

lative

In

du

ctio

n [

%]


−11 −10 −9 −8 −7 −6 −5

10

20

30

40

50

60

70

80

90

100

log10(M)

Re

lative

In

du

ctio

n [

%]


−11 −10 −9 −8 −7 −6 −5 −40

10

20

30

40

50

60

70

80

90

100

log10(M)

Re

lative

In

du

ctio

n [

%]

TI−BDS2CG, run 2, BDS

−11 −10 −9 −8 −7 −6 −5 −40

10

20

30

40

50

60

70

80

90

100

log10(M)

Re

lative

In

du

ctio

n [

%]


−11 −10 −9 −8 −7 −6 −5 −40

10

20

30

40

50

60

70

80

90

100

log10(M)

Re

lative

In

du

ctio

n [

%]



82

−11 −10 −9 −8 −7 −6 −5 −40

10

20

30

40

50

60

70

80

90

100

log10(M)

Rela

tive Induction [%

]

TI−CIT2AE, Citoxlab

run 2

run 7

run 11

DHT

−11 −10 −9 −8 −7 −6 −5 −40

10

20

30

40

50

60

70

80

90

100

110

log10(M)

Rela

tive I

nduction [%

]

TI−ENV2HD, Envigo

run 1

run 2

run 5

DHT

−11 −10 −9 −8 −7 −6 −5

10

20

30

40

50

60

70

80

90

100

log10(M)

Re

lative

In

du

ctio

n [

%]

TI−3HX, RISE

run 3

run 5

run 7

DHT

−11 −10 −9 −8 −7 −6 −5 −40

10

20

30

40

50

60

70

80

90

100

log10(M)

Rela

tive Induction [%

]

TI−BDS2CG, BDS

run 2

run 4

run 6

DHT


−11 −10 −9 −8 −7 −6 −5 −40

10

20

30

40

50

60

70

80

90

100

110

log10(M)

Re

lative

In

ductio

n [

%]


Citoxlab

Envigo

RISE

BDS

DHT


83

Citoxlab

Envigo

RISE

BDS

run2

run7

run11

run1

run2

run5

run3

run5

run7

run2

run4

run6

[µM]

[mg/ml]

PRE

PRE

PRE

PRE

PRE

COM

COM

COM

COM

PRE

PRE

PRE

3.6e-6

1.5e-9

0(0)

1.2e-5

5e-9

0(0)

0(0.1)

-0.1(0.1)

0.5(0.6)

0(0.1)-0.3(0)

-0.4(0)

3.6e-5

1.5e-8

0(0)

1.2e-4

5e-8

0(0.1)

0(0.1)

0(0)

0.2(0.4)

-0.1(0.1)-0.3(0)

-0.4(0)

3.6e-4

1.5e-7

0(0)

1.2e-3

5e-7

0(0)

0(0.1)

0(0.1)

0.4(0.4)

-0.1(0.1)-0.3(0.1)-0.4(0)

3.24e-3

1.35e-6

0(0.2)

0(0.3)0.5(0.2)

3.6e-3

1.5e-6

0.1(0.1)

0.3(0.1)

1.08e-2

4.5e-6

0.6(0.1)

0.9(0)

8(7)

1.2e-2

5e-6

1(0.1)0.6(0.1)

0.5(0.2)

2.4(1.2)1.2(0.1)

0.8(0.2)0.5(0.1)0.2(0.1)

3.24e-2

1.35e-5

2.4(0.3)

2.5(0.1)

3.4(0.9)

3.6e-2

1.5e-5

1.3(0.1)

3.1(0.1)

1.08e-1

4.5e-5

5(0.3)5.4(0.4)

5.6(1.2)

1.2e-1

5e-5

5.8(1.1)

4.2(0.6)

4.2(1)

6.7(2.1)

6(0.9)

5.3(0.7)3.7(0.2)3.2(0.3)

3.24e-1

1.35e-4

6.2(0.3)

6.6(0.1)

7(1.6)

3.6e-1

1.5e-4

5(0.4)

8(0.8)

1.08

4.5e-4

7.4(0.3)

8(0.2)7.6(0.5)

1.2

5e-4

7.2(0.4)

7.2(1.1)

6.6(1.3)

9.6(3)

8.4(0.4)

8(0.1)5.6(0.2)5.2(0.1)

3.24

1.35e-3

8.2(0.8)

8.6(0.3)

8.9(0.6)

3.6

1.5e-3

6.4(0.4)

9.1(1)

10.8

4.5e-3

8.1(0.2)

8.7(0.6)

9.1(0.3)

125e-3

8(0.5)8.3(0.6)

7.7(0.7)

10.3(2.8)9.1(0.4)

8.2(0.8)6.1(0.4)5.7(0.2)

36.01

1.5e-2

6.7(0.4)

120.02

5e-2

3.3(0.2)

cyt/excl

0.7(0.4)

0.5(0.6)

1.2(0.1)1.3(0.2)1.2(0.1)

log 1

0(PC10)[mg/ml]

-3.12

log 1

0(EC50)[mg/ml]

-5.16


84

C.4 Test item 4

−11 −10 −9 −8 −7 −6 −5

10

20

30

40

50

60

70

80

90

100

log10(M)

Re

lative

In

du

ctio

n [

%]

TI−CIT2NX, run 5, Citoxlab

−11 −10 −9 −8 −7 −60

10

20

30

40

50

60

70

80

90

100

log10(M)

Re

lative

In

du

ctio

n [

%]


−11 −10 −9 −8 −7 −6 −5

10

20

30

40

50

60

70

80

90

100

110

log10(M)

Re

lative

In

du

ctio

n [

%]


−11 −10 −9 −8 −7

10

20

30

40

50

60

70

80

90

100

110

log10(M)

Re

lative

In

du

ctio

n [

%]

TI−ENV2ET, run 3, Envigo

−11 −10 −9 −8 −7

10

20

30

40

50

60

70

80

90

100

log10(M)

Re

lative

In

du

ctio

n [

%]


−11 −10 −9 −8 −70

10

20

30

40

50

60

70

80

90

100

log10(M)

Re

lative

In

du

ctio

n [

%]


−11 −10 −9 −8 −7 −60

10

20

30

40

50

60

70

80

90

100

log10(M)

Re

lative

In

du

ctio

n [

%]

TI−1KX, run 5, RISE

−11 −10 −9 −8 −7 −60

10

20

30

40

50

60

70

80

90

100

log10(M)

Re

lative

In

du

ctio

n [

%]


−11 −10 −9 −8 −7 −60

10

20

30

40

50

60

70

80

90

100

log10(M)

Re

lative

In

du

ctio

n [

%]


−11 −10 −9 −8 −7 −6

10

20

30

40

50

60

70

80

90

100

log10(M)

Rela

tive Induction [%

]

TI−BDS2LN, run 7, BDS

−11 −10 −9 −8 −7 −6

10

20

30

40

50

60

70

80

90

100

log10(M)

Rela

tive Induction [%

]


−11 −10 −9 −8 −7 −6

10

20

30

40

50

60

70

80

90

100

log10(M)

Rela

tive Induction [%

]



85

−11 −10 −9 −8 −7 −6 −50

10

20

30

40

50

60

70

80

90

100

110

log10(M)

Rela

tive Induction [%

]

TI−CIT2NX, Citoxlab

run 5

run 13

run 16

DHT

−11 −10 −9 −8 −70

10

20

30

40

50

60

70

80

90

100

110

log10(M)

Rela

tive Induction [%

]

TI−ENV2ET, Envigo

run 3

run 5

run 7

DHT

−11 −10 −9 −8 −7 −6

10

20

30

40

50

60

70

80

90

100

log10(M)

Rela

tive Induction [%

]

TI−1KX, RISE

run 5

run 7

run 8

DHT

−11 −10 −9 −8 −7 −6

10

20

30

40

50

60

70

80

90

100

log10(M)

Rela

tive I

nduction [%

]

TI−BDS2LN, BDS

run 7

run 8

run 10

DHT


−11 −10 −9 −8 −7 −6 −50

10

20

30

40

50

60

70

80

90

100

110

log10(M)

Rela

tive

In

du

ctio

n [

%]


Citoxlab

Envigo

RISE

BDS

DHT


86

Citoxlab

Envigo

RISE

BDS

run5

run13

run16

run3

run5

run7

run5

run7

run8

run7

run8

run10

[µM]

[mg/ml]

COM

COM

COM

COM

COM

COM

COM

COM

COM

COM

COM

COM

1.16e-4

4.5e-8

0.6(0.4)

9.6(0.7)

0.4(0.4)

0.1(0.2)

0.1(0.1)

0.7(0)

1.66e-4

6.4e-8

0.1(0)

3.49e-4

1.35e-7

0.8(0.3)

0.9(0.1)

1.4(0.2)

3.88e-4

1.5e-7

1.7(0.7)

25.6(0.6)

1.5(0.3)

1.1(0.1)

0.9(0.3)

1.5(0.2)

8.28e-4

3.2e-7

1.1(0.2)

1.16e-3

4.5e-7

1.8(0.2)

13.1(2.3)

40.7(4.4)

5.5(0.7)

5(0.7)

6.3(0.8)

7.5(2.5)

3.8(0.6)

4.8(0.2)

5.9(0.5)

3.49e-3

1.35e-6

14.4(1.1)

14.4(0.4)

18.1(2)

3.88e-3

1.5e-6

10.1(0.3)

9.7(0.4)

25.5(2.4)

47.6(3)

19.4(2.2)

15.7(1.4)

18.1(1.5)

21.2(1)

4.14e-3

1.6e-6

8.9(0.6)

1.16e-2

4.5e-6

21.1(4.3)

35.6(4.5)

48.3(4.1)

33(1.9)

29(1.3)

28.1(2)

cyt/excl

26.8(2.7)

28.3(1.7)

30(0.5)

1.29e-2

5e-6

19.3(1.5)

2.07e-2

8e-6

22.9(2.4)

3.49e-2

1.35e-5

34.9(1.4)

33.6(1.7)

36.2(2)

3.88e-2

1.5e-5

27.2(0.7)

28.6(0.8)

44.6(9.7)

64.6(8.5)

41(2.6)

34.9(1.3)

38.1(2.5)

40.4(2.8)

1.03e-1

4e-5

30.4(0.9)

1.16e-1

4.5e-5

31.2(1.5)

48.4(7.3)

55.6(6.8)

47.7(11.1)

38.3(2.1)

42(3)

43.9(3.2)

41.2(4.1)

37.1(2.3)

40.8(3.2)

1.29e-1

5e-5

31.9(2.1)

3.49e-1

1.35e-4

43.4(1.9)

40.7(3.1)

41.9(2.2)

3.88e-1

1.5e-4

32.3(0.7)

34.4(4.4)

54.8(4)

60.3(2.4)

45.9(2.6)

41.3(2.2)

46.4(2.4)

46.6(2.2)

5.17e-1

2e-4

32.2(1.4)

1.16

4.5e-4

36.4(1.3)

45.2(0.8)

51.7(6.8)

50.6(5)

48.6(4.7)

46.2(3.9)

49.3(2.8)

1.29

5e-4

38.1(2.5)

2.59

1e-3

41(2.6)

3.88

1.5e-3

41.7(1)

44.6(2.8)

51.6(1.5)

52.8(3.4)

53.1(2.3)

12.94

5e-3

36.8(0.3)

39.2(1.7)

log 1

0(PC10)[mg/ml]

-5.81

-5.74

-6.46

-7.33

-6.14

-6.06

-6.17

-6.24

-6.05

-6.06

-6.17

log 1

0(EC50)[mg/ml]

-5.25

-5.25

-5.17

-5.71

-6.64

-5.67

-5.51

-5.43

-5.63

-5.44

-5.54

-5.6


87

C.5 Test item 5

−11 −10 −9 −8 −7 −6 −5 −40

10

20

30

40

50

60

70

80

90

100

log10(M)

Rela

tive Induction [%

]TI−CIT2RD, run 1, Citoxlab

−11 −10 −9 −8 −7 −6 −50

10

20

30

40

50

60

70

80

90

100

log10(M)

Re

lative

In

du

ctio

n [

%]

TI−CIT2RD, run 7, Citoxlab

−11 −10 −9 −8 −7 −6 −50

10

20

30

40

50

60

70

80

90

100

log10(M)

Re

lative

In

du

ctio

n [

%]


−11 −10 −9 −8 −7 −6 −5 −40

10

20

30

40

50

60

70

80

90

100

110

log10(M)

Re

lative

In

du

ctio

n [

%]

TI−ENV2YA, run 2, Envigo

−11 −10 −9 −8 −7 −6 −5 −40

10

20

30

40

50

60

70

80

90

100

log10(M)

Re

lative

In

du

ctio

n [

%]


−11 −10 −9 −8 −7 −6 −5 −40

10

20

30

40

50

60

70

80

90

100

log10(M)

Re

lative

In

du

ctio

n [

%]


−11 −10 −9 −8 −7 −6 −50

10

20

30

40

50

60

70

80

90

100

log10(M)

Re

lative

In

du

ctio

n [

%]

TI−5MZ, run 1, RISE

−11 −10 −9 −8 −7 −6 −50

10

20

30

40

50

60

70

80

90

100

log10(M)

Re

lative

In

du

ctio

n [

%]


−11 −10 −9 −8 −7 −6 −50

10

20

30

40

50

60

70

80

90

100

log10(M)

Re

lative

In

du

ctio

n [

%]


−11 −10 −9 −8 −7 −6 −5 −40

10

20

30

40

50

60

70

80

90

100

log10(M)

Re

lative

In

du

ctio

n [

%]

TI−BDS2CW, run 2, BDS

−11 −10 −9 −8 −7 −6 −5 −40

10

20

30

40

50

60

70

80

90

100

log10(M)

Re

lative

In

du

ctio

n [

%]


−11 −10 −9 −8 −7 −6 −5 −40

10

20

30

40

50

60

70

80

90

100

log10(M)

Re

lative

In

du

ctio

n [

%]



88

−11 −10 −9 −8 −7 −6 −5 −40

10

20

30

40

50

60

70

80

90

100

log10(M)

Rela

tive Induction [%

]

TI−CIT2RD, Citoxlab

run 1

run 7

run 11

DHT

−11 −10 −9 −8 −7 −6 −5 −40

10

20

30

40

50

60

70

80

90

100

110

log10(M)

Rela

tive Induction [%

]

TI−ENV2YA, Envigo

run 2

run 4

run 6

DHT

−11 −10 −9 −8 −7 −6 −50

10

20

30

40

50

60

70

80

90

100

log10(M)

Rela

tive Induction [%

]

TI−5MZ, RISE

run 1

run 2

run 6

DHT

−11 −10 −9 −8 −7 −6 −5 −40

10

20

30

40

50

60

70

80

90

100

log10(M)

Rela

tive Induction [%

]

TI−BDS2CW, BDS

run 2

run 3

run 5

DHT


−11 −10 −9 −8 −7 −6 −5 −4

0

10

20

30

40

50

60

70

80

90

100

110

log10(M)

Rela

tive

In

du

ctio

n [

%]


Citoxlab

Envigo

RISE

BDS

DHT


89

Citoxlab

Envigo

RISE

BDS

run1

run7

run11

run2

run4

run6

run1

run2

run6

run2

run3

run5

[µM]

[mg/ml]

PRE

PRE

PRE

PRE

PRE

PRE

PRE

PRE

PRE

PRE

PRE

PRE

6.57e-6

1.5e-9

0(0)

0(0)

-2.9(0.2)-0.2(0.1)

0(0.2)

2.19e-5

5e-9

0(0)

-0.1(0.2)0.2(0.2)

0(0)

0(0)

-0.2(0.1)0.1(0)

6.57e-5

1.5e-8

0(0)

0(0)

-2.9(0.2)-0.1(0.1)-0.1(0.1)

2.19e-4

5e-8

0.1(0)

0.6(0.9)0.7(0.1)

15.8(27.5)

0(0.1)-0.2(0.1)0.1(0.1)

6.57e-4

1.5e-7

0(0)

0(0)

-2.9(0)

-0.2(0.1)

0(0.3)

2.19e-3

5e-7

0.1(0)

0.3(0.5)0.1(0.1)-0.4(0.2)

0(0)

-0.3(0)

0.1(0)

6.57e-3

1.5e-6

0(0)

0.2(0.1)

-3(0)

-0.2(0.2)-0.1(0.1)

2.19e-2

5e-6

0.1(0.1)

0(0.4)

0(0.2)-0.2

(0)

0(0)

-0.3(0.1)0.1(0.1)

6.57e-2

1.5e-5

0(0)

0(0)

-2.9(0.2)-0.1(0.2)-0.3(0.3)

2.19e-1

5e-5

0(0)

-0.1(0.5)-0.4(0.3)

0.1(0.2)

0(0)

-0.3(0)

0(0)

6.57e-1

1.5e-4

0(0.1)

0(0)

-3(0.2)-0.1(0.2)-0.3(0.1)

2.19

5e-4

0(0)

-0.5(0.3)0.2(0.1)

0(0.1)

0(0)

-0.3(0)

0.1(0.1)

6.57

1.5e-3

0(0.1)

0.1(0)

-2.9(0.1)

0(0.1)-0.5(0.1)

21.9

5e-3

0.1(0)

-0.8(0.2)0.3(0)

0.2(0.5)

0.1(0)

-0.1(0.1)0.3(0)

65.7

1.5e-2

0(0.1)

-0.1(0)

-2.7(0.1)-0.1(0.1)-0.3(0.2)

219.01

5e-2

cyt/excl

-1.8(0.1)-0.6(0)

-0.3(0.2)

-0.5(0)

-0.3(0.1)-0.1(0.1)

log 1

0(PC10)[mg/ml]

-8.07

log 1

0(EC50)[mg/ml]

na


90

C.6 Test item 6

−11 −10 −9 −8 −7 −6 −5 −40

10

20

30

40

50

60

70

80

90

100

log10(M)

Re

lative

In

du

ctio

n [

%]

TI−CIT2YY, run 1, Citoxlab

−11 −10 −9 −8 −7 −6 −5 −40

10

20

30

40

50

60

70

80

90

100

log10(M)

Re

lative

In

du

ctio

n [

%]


−11 −10 −9 −8 −7 −6 −5 −40

10

20

30

40

50

60

70

80

90

100

log10(M)

Re

lative

In

du

ctio

n [

%]


−11 −10 −9 −8 −7 −6 −5 −40

10

20

30

40

50

60

70

80

90

100

log10(M)

Re

lative

In

du

ctio

n [

%]

TI−ENV2DF, run 1, Envigo

−11 −10 −9 −8 −7 −6 −5 −40

10

20

30

40

50

60

70

80

90

100

110

log10(M)

Re

lative

In

du

ctio

n [

%]


−11 −10 −9 −8 −7 −6 −5 −4

10

20

30

40

50

60

70

80

90

100

log10(M)

Re

lative

In

du

ctio

n [

%]


−11 −10 −9 −8 −7 −6 −5 −40

10

20

30

40

50

60

70

80

90

100

log10(M)

Re

lative

In

du

ctio

n [

%]

TI−7WS, run 5, RISE

−11 −10 −9 −8 −7 −6 −5 −40

10

20

30

40

50

60

70

80

90

100

log10(M)

Re

lative

In

du

ctio

n [

%]


−11 −10 −9 −8 −7 −6 −5 −40

10

20

30

40

50

60

70

80

90

100

log10(M)

Re

lative

In

du

ctio

n [

%]


−11 −10 −9 −8 −7 −6 −5 −40

10

20

30

40

50

60

70

80

90

100

log10(M)

Re

lative

In

du

ctio

n [

%]

TI−BDS2QX, run 1, BDS

−11 −10 −9 −8 −7 −6 −5 −40

10

20

30

40

50

60

70

80

90

100

log10(M)

Re

lative

In

du

ctio

n [

%]


−11 −10 −9 −8 −7 −6 −5 −40

10

20

30

40

50

60

70

80

90

100

log10(M)

Re

lative

In

du

ctio

n [

%]



91

−11 −10 −9 −8 −7 −6 −5 −40

10

20

30

40

50

60

70

80

90

100

log10(M)

Rela

tive Induction [%

]

TI−CIT2YY, Citoxlab

run 1

run 7

run 11

DHT

−11 −10 −9 −8 −7 −6 −5 −40

10

20

30

40

50

60

70

80

90

100

110

log10(M)

Rela

tive Induction [%

]

TI−ENV2DF, Envigo

run 1

run 2

run 5

DHT

−11 −10 −9 −8 −7 −6 −5 −40

10

20

30

40

50

60

70

80

90

100

log10(M)

Rela

tive Induction [%

]

TI−7WS, RISE

run 5

run 7

run 8

DHT

−11 −10 −9 −8 −7 −6 −5 −40

10

20

30

40

50

60

70

80

90

100

log10(M)

Rela

tive Induction [%

]

TI−BDS2QX, BDS

run 1

run 3

run 5

DHT


−11 −10 −9 −8 −7 −6 −5 −40

10

20

30

40

50

60

70

80

90

100

110

log10(M)

Re

lative

In

du

ctio

n [

%]


Citoxlab

Envigo

RISE

BDS

DHT


92

Citoxlab

Envigo

RISE

BDS

run1

run7

run11

run1

run2

run5

run5

run7

run8

run1

run3

run5

[µM]

[mg/ml]

PRE

PRE

PRE

PRE

PRE

COM

COM

COM

COM

PRE

PRE

PRE

1.16e-5

5e-9

0(0)

0(0)

0(0)

0.1(0.1)

0.3(0.3)

0(0.2)-0.2(0.1)

0(0)

1.16e-4

5e-8

0(0)

0(0)

0(0)

0.2(0.2)

0.2(0.4)

-0.1(0.1)-0.3(0)

0(0.1)

1.16e-3

5e-7

0(0)

0(0)

0(0.1)0.2(0.3)

0.3(0.2)

-0.1(0.1)-0.3(0)

0(0)

1.16e-2

5e-6

0.1(0)

0(0)

1.1(0.2)

0.4(0.5)

0.3(0.3)

0(0.2)-0.3(0)

0(0)

3.49e-2

1.5e-5

0.1(0)

-0.1(0.1)0.2(0.2)0.4(0.5)

1.16e-1

5e-5

0.2(0)

0.1(0)

0(0)

0.3(0.2)

0.2(0.2)0.3(0.2)

0(0.1)0.2(0.2)0.3(0.3)

0.1(0.1)-0.2(0)

0.1(0)

3.49e-1

1.5e-4

0.4(0.1)

0.2(0.1)-0.1(0.1)0.2(0.2)

1.16

5e-4

0.3(0)

0.2(0)

0.1(0.1)

0.3(0.1)

-0.2(0.2)0.5(0.1)

0.1(0.1)-0.1(0.1)0.2(0.3)

0.2(0.2)-0.1(0)

0.2(0.1)

3.49

1.5e-3

0.7(0.3)

0.3(0.1)0.3(0.2)0.3(0.3)

11.62

5e-3

0.9(0)

0.7(0.1)

0.6(0.1)

1(0.2)0.9(0.4)1.5(0.2)

0.7(0.1)

1(0.2)0.9(0.3)

1.1(0.2)0.3(0.1)0.7(0.1)

34.85

1.5e-2

3.1(0.1)

2.1(0.3)2.2(0.3)2.1(0.4)

116.17

5e-2

0.5(0)

0.7(0.2)

0.6(0.1)

1.1(0.1)

1.7(0.4)1.4(0.1)

0.4(0.1)0.4(0.2)0.9(0.4)

0.8(0.2)

1(0.1)1.6(0)

log 1

0(PC10)[mg/ml]

log 1

0(EC50)[mg/ml]


93

C.7 Test item 7

−11 −10 −9 −8 −7 −6 −50

10

20

30

40

50

60

70

80

90

100

log10(M)

Rela

tive Induction [%

]TI−CIT2RK, run 2, Citoxlab

−11 −10 −9 −8 −7 −6 −50

10

20

30

40

50

60

70

80

90

100

log10(M)

Rela

tive Induction [%

]

TI−CIT2RK, run 7, Citoxlab

−12 −11 −10 −9 −8 −7 −60

10

20

30

40

50

60

70

80

90

100

log10(M)

Re

lative

In

du

ctio

n [

%]


−11 −10 −9 −8 −7 −6 −50

10

20

30

40

50

60

70

80

90

100

log10(M)

Re

lative

In

du

ctio

n [

%]

TI−ENV2VZ, run 1, Envigo

−12 −11 −10 −9 −8 −7 −60

10

20

30

40

50

60

70

80

90

100

110

log10(M)

Re

lative

In

du

ctio

n [

%]


−12 −11 −10 −9 −8 −7 −60

10

20

30

40

50

60

70

80

90

100

log10(M)

Re

lative

In

du

ctio

n [

%]


−11 −10 −9 −8 −7 −6 −50

10

20

30

40

50

60

70

80

90

100

log10(M)

Rela

tive Induction [%

]

TI−9YP, run 1, RISE

−12 −11 −10 −9 −8 −7 −60

10

20

30

40

50

60

70

80

90

100

log10(M)

Re

lative

In

du

ctio

n [

%]


−12 −11 −10 −9 −8 −7 −60

10

20

30

40

50

60

70

80

90

100

log10(M)

Re

lative

In

du

ctio

n [

%]


−11 −10 −9 −8 −7 −6 −50

10

20

30

40

50

60

70

80

90

100

log10(M)

Re

lative

In

du

ctio

n [

%]

TI−BDS2MU, run 1, BDS

−11 −10 −9 −8 −7 −6 −50

10

20

30

40

50

60

70

80

90

100

log10(M)

Re

lative

In

du

ctio

n [

%]


−11 −10 −9 −8 −7 −6 −50

10

20

30

40

50

60

70

80

90

100

log10(M)

Re

lative

In

du

ctio

n [

%]



94

−12 −11 −10 −9 −8 −7 −6 −50

10

20

30

40

50

60

70

80

90

100

log10(M)

Rela

tive Induction [%

]

TI−CIT2RK, Citoxlab

run 2

run 7

run 12

DHT

−12 −11 −10 −9 −8 −7 −6 −50

10

20

30

40

50

60

70

80

90

100

110

log10(M)

Rela

tive Induction [%

]

TI−ENV2VZ, Envigo

run 1

run 2

run 4

DHT

−12 −11 −10 −9 −8 −7 −6 −50

10

20

30

40

50

60

70

80

90

100

log10(M)

Rela

tive Induction [%

]

TI−9YP, RISE

run 1

run 4

run 6

DHT

−11 −10 −9 −8 −7 −6 −50

10

20

30

40

50

60

70

80

90

100

log10(M)

Rela

tive Induction [%

]

TI−BDS2MU, BDS

run 1

run 3

run 5

DHT


−12 −11 −10 −9 −8 −7 −6 −5

0

10

20

30

40

50

60

70

80

90

100

110

log10(M)

Re

lative

In

ductio

n [

%]


Citoxlab

Envigo

RISE

BDS

DHT


95

Citoxlab

Envigo

RISE

BDS

run2

run7

run12

run1

run2

run4

run1

run4

run6

run1

run3

run5

[µM]

[mg/ml]

PRE

PRE

PRE

PRE

PRE

PRE

PRE

PRE

PRE

PRE

PRE

PRE

1.69e-7

5e-11

0(0.1)0.2(0.1)

4.55e-7

1.35e-10

0(0)

5.06e-7

1.5e-10

0.4(0.1)

0(0.2)

1.52e-6

4.5e-10

0(0)

1.69e-6

5e-10

-2.9(0.1)

0(0.2)

0(0.3)

4.55e-6

1.35e-9

0(0)

5.06e-6

1.5e-9

0(0)

-0.1(0.1)3.6(1.1)0.1(0.1)

0(0)

-0.2(0.1)

0(0)

1.52e-5

4.5e-9

0(0)

1.69e-5

5e-9

-2.6(0.2)-0.3(0.2)-0.1(0.1)

4.55e-5

1.35e-8

0(0.1)

5.06e-5

1.5e-8

0(0)

0(0.1)0.4(0.2)0.1(0.2)

0(0.1)-0.3(0.1)

0(0.1)

1.52e-4

4.5e-8

0(0)

1.69e-4

5e-8

-2.8(0.2)-0.1(0.1)-0.2(0.3)

4.55e-4

1.35e-7

0(0.1)

5.06e-4

1.5e-7

0(0)

-0.1(0.1)0.3(0.3)-0.1(0.1)

0(0.1)-0.3(0.1)

0(0)

1.52e-3

4.5e-7

0(0.1)

1.69e-3

5e-7

-2.8(0.1)0.1(0.1)-0.1(0.1)

4.55e-3

1.35e-6

0(0)

5.06e-3

1.5e-6

0(0)

8.1(1.2)0.6(0.2)

0(0.1)

0(0)

-0.3(0)

0(0)

1.52e-2

4.5e-6

0(0)

1.69e-2

5e-6

-2.8(0.1)-0.1(0.2)-0.2(0.3)

4.55e-2

1.35e-5

0(0.1)

5.06e-2

1.5e-5

0(0)

-0.1(0.1)0.4(0.2)0.1(0.2)

0(0.1)-0.2(0.1)

0(0)

1.52e-1

4.5e-5

0(0)

1.69e-1

5e-5

-2.5(0.6)

0(0.1)-0.2(0.3)

4.55e-1

1.35e-4

0(0.1)

5.06e-1

1.5e-4

0(0)

-0.1(0.1)1.7(1.3)0.2(0.2)

0(0.1)-0.3(0)

0(0.1)

1.52

4.5e-4

0(0)

1.69

5e-4

-2.7(0.1)-0.2(0.3)-0.2(0)

4.55

1.35e-3

-0.1(0)

5.06

1.5e-3

-0.2(0)

-0.1(0.1)-0.7(0.3)2.7(0.3)

0(0)

-0.3(0)

0(0)

15.18

4.5e-3

cyt/excl

16.86

5e-3

cyt/excl

50.59

1.5e-2

cyt/excl

-1.1(0)

-0.9(0)

-0.7(0)

-0.8(0)

log 1

0(PC10)[mg/ml]

log 1

0(EC50)[mg/ml]


96

C.8 Test item 8

−11 −10 −9 −8 −7 −6 −50

10

20

30

40

50

60

70

80

90

100

log10(M)

Rela

tive Induction [%

]TI−CIT2XK, run 2, Citoxlab

−12 −11 −10 −9 −8 −7 −60

10

20

30

40

50

60

70

80

90

100

log10(M)

Re

lative

In

du

ctio

n [

%]

TI−CIT2XK, run 6, Citoxlab

−12 −11 −10 −9 −8 −7 −60

10

20

30

40

50

60

70

80

90

100

log10(M)

Re

lative

In

du

ctio

n [

%]


−11 −10 −9 −8 −7 −6 −50

10

20

30

40

50

60

70

80

90

100

log10(M)

Re

lative

In

du

ctio

n [

%]


−12 −11 −10 −9 −8 −7 −60

10

20

30

40

50

60

70

80

90

100

110

log10(M)

Re

lative

In

du

ctio

n [

%]


−12 −11 −10 −9 −8 −7 −60

10

20

30

40

50

60

70

80

90

100

log10(M)

Re

lative

In

du

ctio

n [

%]


−11 −10 −9 −8 −7 −6 −5

0

10

20

30

40

50

60

70

80

90

100

log10(M)

Rela

tive Induction [%

]

TI−6NS, run 1, RISE

−12 −11 −10 −9 −8 −7 −60

10

20

30

40

50

60

70

80

90

100

log10(M)

Re

lative

In

du

ctio

n [

%]


−12 −11 −10 −9 −8 −7 −60

10

20

30

40

50

60

70

80

90

100

log10(M)

Re

lative

In

du

ctio

n [

%]


−11 −10 −9 −8 −7 −6 −50

10

20

30

40

50

60

70

80

90

100

log10(M)

Re

lative

In

du

ctio

n [

%]

TI−BDS2WW, run 2, BDS

−11 −10 −9 −8 −7 −6 −50

10

20

30

40

50

60

70

80

90

100

log10(M)

Re

lative

In

du

ctio

n [

%]


−11 −10 −9 −8 −7 −6 −50

10

20

30

40

50

60

70

80

90

100

log10(M)

Re

lative

In

du

ctio

n [

%]



97

−12 −11 −10 −9 −8 −7 −6 −50

10

20

30

40

50

60

70

80

90

100

log10(M)

Rela

tive Induction [%

]

TI−CIT2XK, Citoxlab

run 2

run 6

run 10

DHT

−12 −11 −10 −9 −8 −7 −6 −50

10

20

30

40

50

60

70

80

90

100

110

log10(M)

Rela

tive Induction [%

]

TI−ENV2QF, Envigo

run 1

run 2

run 4

DHT

−12 −11 −10 −9 −8 −7 −6 −5

0

10

20

30

40

50

60

70

80

90

100

log10(M)

Rela

tive Induction [%

]

TI−6NS, RISE

run 1

run 4

run 6

DHT

−11 −10 −9 −8 −7 −6 −50

10

20

30

40

50

60

70

80

90

100

log10(M)

Rela

tive Induction [%

]

TI−BDS2WW, BDS

run 2

run 4

run 6

DHT


−12 −11 −10 −9 −8 −7 −6 −5

0

10

20

30

40

50

60

70

80

90

100

110

log10(M)

Re

lative

In

ductio

n [

%]


Citoxlab

Envigo

RISE

BDS

DHT


98

Citoxlab

Envigo

RISE

BDS

run2

run6

run10

run1

run2

run4

run1

run4

run6

run2

run4

run6

[µM]

[mg/ml]

PRE

PRE

PRE

PRE

PRE

PRE

PRE

PRE

PRE

PRE

PRE

PRE

1.35e-7

5e-11

0(0.1)

0(0.1)

4.04e-7

1.5e-10

0(0)-0.9(0)

0.3(0.5)

0.8(0)

1.35e-6

5e-10

0(0)

cyt/excl

0(0.1)

0(0.4)

4.04e-6

1.5e-9

0(0)-0.8(0)-0.1(0.1)0.3(0.4)

0.1(0.2)

0.1(0.1)-0.2(0.1)

0(0)

1.35e-5

5e-9

2.1(0.2)

-3(0.2)-0.2(0.1)-0.4(0.3)

4.04e-5

1.5e-8

0(0)-0.8(0)-0.1

(0)

0.4(0)

0.1(0.1)

0.1(0.1)-0.3(0)

0(0)

1.35e-4

5e-8

0(0)

-3.2(0.1)-0.1(0.1)-0.3(0.5)

4.04e-4

1.5e-7

0(0)-0.9(0)-0.2

(0)

0.2(0.2)

0.1(0.1)

0.1(0.1)-0.2(0)

0(0)

1.35e-3

5e-7

0.1(0)

-3.3(0.1)-0.1(0)

-0.2(0.3)

4.04e-3

1.5e-6

0.1(0)

-0.6(0)

19.2(24)

0.4(0.5)

0.1(0.1)

0.1(0)

-0.2(0)

0(0)

1.35e-2

5e-6

0.1(0)

-3.2(0.1)-0.1(0.1)-0.5(0.2)

4.04e-2

1.5e-5

0.1(0)

-0.9(0)

25.4(38.3)

1(0.6)0.2(0.1)

0.1(0)

-0.2(0.1)

0(0)

1.35e-1

5e-5

0(0)

-3.1(0.3)-0.2(0.2)-0.3(0.1)

4.04e-1

1.5e-4

0(0)-0.8(0)

8.2(11.6)

3.7(3)

0.1(0.1)

0(0.1)-0.2(0)

0(0.1)

1.35

5e-4

0(0)

-3.5(0.1)-0.2(0.1)-0.4(0.4)

4.04

1.5e-3

0(0)

-1(0)

29.2(10.6)

1.9(1.9)

-0.1(0.1)

-0.1(0)

-0.2(0)

-0.2(0)

13.46

5e-3

cyt/excl

cyt/excl

40.38

1.5e-2

-1.1

(0)

-0.9(0)

-0.8(0.1)-0.8(0)

log 1

0(PC10)[mg/ml]

nalog 1

0(EC50)[mg/ml]

na


99

C.9 Test item 9

−11 −10 −9 −8 −7 −6 −50

10

20

30

40

50

60

70

80

90

100

log10(M)

Re

lative

In

du

ctio

n [

%]

TI−CIT2LK, run 2, Citoxlab

−11 −10 −9 −8 −7 −6 −50

10

20

30

40

50

60

70

80

90

100

log10(M)

Re

lative

In

du

ctio

n [

%]


−11 −10 −9 −8 −7 −6 −50

10

20

30

40

50

60

70

80

90

100

log10(M)

Re

lative

In

du

ctio

n [

%]


−11 −10 −9 −8 −7 −6 −50

10

20

30

40

50

60

70

80

90

100

log10(M)

Re

lative

In

du

ctio

n [

%]

TI−ENV2ZR, run 1, Envigo

−11 −10 −9 −8 −7 −6 −50

10

20

30

40

50

60

70

80

90

100

110

log10(M)

Re

lative

In

du

ctio

n [

%]


−11 −10 −9 −8 −7 −6 −50

10

20

30

40

50

60

70

80

90

100

log10(M)

Re

lative

In

du

ctio

n [

%]


−11 −10 −9 −8 −7 −6 −5

0

10

20

30

40

50

60

70

80

90

100

log10(M)

Re

lative

In

du

ctio

n [

%]

TI−2SH, run 1, RISE

−11 −10 −9 −8 −7 −6 −50

10

20

30

40

50

60

70

80

90

100

log10(M)

Re

lative

In

du

ctio

n [

%]


−11 −10 −9 −8 −7 −6 −50

10

20

30

40

50

60

70

80

90

100

log10(M)

Re

lative

In

du

ctio

n [

%]


−11 −10 −9 −8 −7 −6 −50

10

20

30

40

50

60

70

80

90

100

log10(M)

Re

lative

In

du

ctio

n [

%]

TI−BDS2YN, run 2, BDS

−11 −10 −9 −8 −7 −6 −50

10

20

30

40

50

60

70

80

90

100

log10(M)

Re

lative

In

du

ctio

n [

%]


−11 −10 −9 −8 −7 −6 −50

10

20

30

40

50

60

70

80

90

100

log10(M)

Re

lative

In

du

ctio

n [

%]



100

−11 −10 −9 −8 −7 −6 −50

10

20

30

40

50

60

70

80

90

100

log10(M)

Rela

tive Induction [%

]


run 2

run 6

run 10

DHT

−11 −10 −9 −8 −7 −6 −50

10

20

30

40

50

60

70

80

90

100

110

log10(M)

Rela

tive Induction [%

]

TI−ENV2ZR, Envigo

run 1

run 2

run 4

DHT

−11 −10 −9 −8 −7 −6 −5

0

10

20

30

40

50

60

70

80

90

100

log10(M)

Rela

tive Induction [%

]

TI−2SH, RISE

run 1

run 2

run 6

DHT

−11 −10 −9 −8 −7 −6 −50

10

20

30

40

50

60

70

80

90

100

log10(M)

Rela

tive Induction [%

]

TI−BDS2YN, BDS

run 2

run 3

run 5

DHT


−11 −10 −9 −8 −7 −6 −5

0

10

20

30

40

50

60

70

80

90

100

110

log10(M)

Rela

tive

In

du

ctio

n [

%]


Citoxlab

Envigo

RISE

BDS

DHT


101

Citoxlab

Envigo

RISE

BDS

run2

run6

run10

run1

run2

run4

run1

run2

run6

run2

run3

run5

[µM]

[mg/ml]

PRE

PRE

PRE

PRE

PRE

PRE

PRE

PRE

PRE

PRE

PRE

PRE

2.32e-6

5e-10

0(0)

0(0)

-1(0)

6.95e-6

1.5e-9

-0.1(0.2)0.5(0.4)

0(0.2)

-3(0.3)-0.1(0.1)-0.3(0.2)0.1(0.1)-0.4(0.1)0.1(0.1)

2.32e-5

5e-9

0(0.1)

0(0)

-1(0)

6.95e-5

1.5e-8

0.1(0.1)0.2(0.3)0.1(0.3)-3.2(0.1)-0.1(0.1)

0(0.2)

0(0)

-0.4(0)

0.1(0)

2.32e-4

5e-8

-0.1(0)

0(0)

-1.1(0)

6.95e-4

1.5e-7

0.1(0.1)0.3(0.3)0.1(0)

-3.2(0.2)-0.2(0.1)-0.1(0.2)

0(0)

-0.4(0)

0.1(0)

2.32e-3

5e-7

0(0)

0(0)

-0.7(0)

6.95e-3

1.5e-6

0.1(0.1)0.3(0.3)

0(0.1)-3.3(0.2)-0.3(0.2)-0.1(0.2)

0(0.1)-0.4(0.1)

0(0)

2.32e-2

5e-6

0(0)

0(0)

-1(0)

6.95e-2

1.5e-5

0.1(0.1)0.3(0.3)-0.1(0.1)-3.5(0)

-0.3(0)

-0.3(0)

-0.1(0)

-0.4(0)

0(0)

2.32e-1

5e-5

0(0.1)0.1(0)

-1(0)

6.95e-1

1.5e-4

0(0.2)0.5(0.7)-0.1(0)

-3.4(0.1)-0.4(0.2)

0(0.1)-0.1(0)

-0.4(0.1)0.1(0.2)

2.32

5e-4

0(0)

0(0)

-1(0)

6.95

1.5e-3

0(0.2)

0(0.3)

0(0.1)-3.3(0.2)-0.4(0.3)-0.1(0.1)

0(0.1)-0.4(0)

0(0.1)

23.18

5e-3

0(0.1)2.5(0.3)

-0.9(0)

69.54

1.5e-2

0(0.2)-0.7(0.3)

0(0.2)-3.3(0.1)-0.2(0.2)-0.4(0.1)-0.1(0.1)-0.3(0)

0.1(0.1)

log 1

0(PC10)[mg/ml]

log 1

0(EC50)[mg/ml]


102

C.10 Test item 10

−11 −10 −9 −8 −7 −6 −50

10

20

30

40

50

60

70

80

90

100

log10(M)

Rela

tive Induction [%

]TI−CIT2GQ, run 1, Citoxlab

−11 −10 −9 −8 −7 −6 −50

10

20

30

40

50

60

70

80

90

100

log10(M)

Rela

tive Induction [%

]

TI−CIT2GQ, run 7, Citoxlab

−12 −11 −10 −9 −8 −7 −60

10

20

30

40

50

60

70

80

90

100

log10(M)

Re

lative

In

du

ctio

n [

%]


−11 −10 −9 −8 −7 −6 −50

10

20

30

40

50

60

70

80

90

100

log10(M)

Re

lative

In

du

ctio

n [

%]

TI−ENV2GK, run 1, Envigo

−11 −10 −9 −8 −7 −6 −50

10

20

30

40

50

60

70

80

90

100

110

log10(M)

Re

lative

In

du

ctio

n [

%]


−11 −10 −9 −8 −7 −6 −50

10

20

30

40

50

60

70

80

90

100

log10(M)

Re

lative

In

du

ctio

n [

%]


−11 −10 −9 −8 −7 −60

10

20

30

40

50

60

70

80

90

100

log10(M)

Re

lative

In

du

ctio

n [

%]

TI−4LR, run 5, RISE

−11 −10 −9 −8 −7 −60

10

20

30

40

50

60

70

80

90

100

log10(M)

Re

lative

In

du

ctio

n [

%]


−11 −10 −9 −8 −7 −60

10

20

30

40

50

60

70

80

90

100

log10(M)

Re

lative

In

du

ctio

n [

%]


−11 −10 −9 −8 −7 −6 −5

10

20

30

40

50

60

70

80

90

100

log10(M)

Re

lative

In

du

ctio

n [

%]

TI−BDS2SD, run 1, BDS

−11 −10 −9 −8 −7 −6 −50

10

20

30

40

50

60

70

80

90

100

log10(M)

Re

lative

In

du

ctio

n [

%]


−11 −10 −9 −8 −7 −6 −50

10

20

30

40

50

60

70

80

90

100

log10(M)

Re

lative

In

du

ctio

n [

%]



103

−12 −11 −10 −9 −8 −7 −6 −50

10

20

30

40

50

60

70

80

90

100

log10(M)

Rela

tive Induction [%

]

TI−CIT2GQ, Citoxlab

run 1

run 7

run 12

DHT

−11 −10 −9 −8 −7 −6 −50

10

20

30

40

50

60

70

80

90

100

110

log10(M)

Rela

tive Induction [%

]

TI−ENV2GK, Envigo

run 1

run 2

run 4

DHT

−11 −10 −9 −8 −7 −60

10

20

30

40

50

60

70

80

90

100

log10(M)

Rela

tive Induction [%

]

TI−4LR, RISE

run 5

run 7

run 8

DHT

−11 −10 −9 −8 −7 −6 −50

10

20

30

40

50

60

70

80

90

100

log10(M)

Rela

tive Induction [%

]

TI−BDS2SD, BDS

run 1

run 3

run 5

DHT


−12 −11 −10 −9 −8 −7 −6 −50

10

20

30

40

50

60

70

80

90

100

110

log10(M)

Rela

tive

In

du

ctio

n [

%]


Citoxlab

Envigo

RISE

BDS

DHT


104

Citoxlab

Envigo

RISE

BDS

run1

run7

run12

run1

run2

run4

run5

run7

run8

run1

run3

run5

[µM]

[mg/ml]

PRE

PRE

PRE

PRE

PRE

PRE

COM

COM

COM

PRE

PRE

PRE

4.55e-7

1.35e-10

-0.1(0)

1.52e-6

4.5e-10

0.1(0)

4.55e-6

1.35e-9

-0.1(0.1)

5.06e-6

1.5e-9

0(0.1)

28.3(48.9)

0.2(0.5)0.1(0.1)

0.1(0)

-0.2(0)

0(0)

1.52e-5

4.5e-9

0(0)

4.55e-5

1.35e-8

0(0.1)

5.06e-5

1.5e-8

0(0)

0.1(0.2)

0.3(0.4)

0(0.1)

0.1(0.1)

-0.2(0)

0(0)

1.52e-4

4.5e-8

0(0)

4.55e-4

1.35e-7

0(0.1)

5.06e-4

1.5e-7

0.1(0.1)

0.2(0.2)

0.4(0.3)-0.1(0.1)

0.1(0)

-0.3(0)

-0.1(0.1)

1.52e-3

4.5e-7

0(0)

0(0.1)-0.1(0.1)0.1(0.1)

4.55e-3

1.35e-6

0(0)

5.06e-3

1.5e-6

0.1(0)

0.3(0.4)

0.4(0.4)0.2(0.2)

0(0.3)

0(0.1)0.1(0.1)

0.1(0.1)

-0.3(0)

0(0)

1.52e-2

4.5e-6

0.1(0.1)

0.1(0.1)

0(0.2)0.6(1.1)

4.55e-2

1.35e-5

0.1(0.1)

5.06e-2

1.5e-5

0.2(0)

1.2(1.3)

0.3(0.2)

0(0.2)0.1(0.1)

0.6(0.3)0.4(0.1)

0.4(0.2)

-0.1(0)

0.1(0)

1.52e-1

4.5e-5

0.3(0)

0.4(0.1)

0.2(0.3)0.4(0.4)

4.55e-1

1.35e-4

0.3(0.1)

5.06e-1

1.5e-4

0.4(0.1)

29.4(49.8)

0.2(0.3)0.6(0.2)0.4(0.2)

0.5(0.3)0.2(0.2)

0.8(0.2)

0(0)

0.3(0)

1.52

4.5e-4

0.6(0)

0.6(0.2)

0.7(0.2)0.5(0.2)

4.55

1.35e-3

1.2(0.1)

5.06

1.5e-3

1.8(0.1)

1.8(0.3)

2.4(0.5)1.9(0.6)1.7(0.2)

2.3(0.1)1.9(0.2)

2.1(0.4)

1(0)

1.4(0.1)

15.18

4.5e-3

cyt/excl

50.61

1.5e-2

cyt/excl

0.9(0.7)-0.5(0.4)1.1(0.8)

1.3(0.1)

1(0.3)1.4(0.5)

log 1

0(PC10)[mg/ml]

-4.53

log 1

0(EC50)[mg/ml]

na


105

C.11 Test item 11

−11 −10 −9 −8 −7 −6 −50

10

20

30

40

50

60

70

80

90

100

log10(M)

Re

lative

In

du

ctio

n [

%]

TI−CIT2ZT, run 4, Citoxlab

−11 −10 −9 −8 −7 −6 −50

10

20

30

40

50

60

70

80

90

100

log10(M)

Re

lative

In

du

ctio

n [

%]


−11 −10 −9 −8 −7 −6 −50

10

20

30

40

50

60

70

80

90

100

log10(M)

Re

lative

In

du

ctio

n [

%]


−11 −10 −9 −8 −7 −6 −5 −40

10

20

30

40

50

60

70

80

90

100

110

log10(M)

Re

lative

In

du

ctio

n [

%]

TI−ENV3AT, run 2, Envigo

−11 −10 −9 −8 −7 −6 −5 −40

10

20

30

40

50

60

70

80

90

100

110

log10(M)

Re

lative

In

du

ctio

n [

%]


−11 −10 −9 −8 −7 −6 −5 −40

10

20

30

40

50

60

70

80

90

log10(M)

Re

lative

In

du

ctio

n [

%]


−11 −10 −9 −8 −7 −6 −5 −40

10

20

30

40

50

60

70

80

90

100

log10(M)

Re

lative

In

du

ctio

n [

%]

TI−11AM, run 1, RISE

−11 −10 −9 −8 −7 −6 −5 −40

10

20

30

40

50

60

70

80

90

100

log10(M)

Re

lative

In

du

ctio

n [

%]


−11 −10 −9 −8 −7 −6 −5 −40

10

20

30

40

50

60

70

80

90

100

log10(M)

Re

lative

In

du

ctio

n [

%]


−11 −10 −9 −8 −7 −6 −5 −40

10

20

30

40

50

60

70

80

90

100

log10(M)

Re

lative

In

du

ctio

n [

%]

TI−BDS2XH, run 1, BDS

−11 −10 −9 −8 −7 −6 −5 −40

10

20

30

40

50

60

70

80

90

100

log10(M)

Re

lative

In

du

ctio

n [

%]


−11 −10 −9 −8 −7 −6 −5 −40

10

20

30

40

50

60

70

80

90

100

log10(M)

Re

lative

In

du

ctio

n [

%]



106

−11 −10 −9 −8 −7 −6 −50

10

20

30

40

50

60

70

80

90

100

log10(M)

Rela

tive Induction [%

]

TI−CIT2ZT, Citoxlab

run 4

run 10

run 15

DHT

−11 −10 −9 −8 −7 −6 −5 −40

10

20

30

40

50

60

70

80

90

100

110

log10(M)

Rela

tive Induction [%

]

TI−ENV3AT, Envigo

run 2

run 4

run 9

DHT

−11 −10 −9 −8 −7 −6 −5 −40

10

20

30

40

50

60

70

80

90

100

log10(M)

Rela

tive Induction [%

]

TI−11AM, RISE

run 1

run 16

run 25

DHT

−11 −10 −9 −8 −7 −6 −5 −40

10

20

30

40

50

60

70

80

90

100

log10(M)

Rela

tive Induction [%

]

TI−BDS2XH, BDS

run 1

run 3

run 5

DHT


−11 −10 −9 −8 −7 −6 −5 −40

10

20

30

40

50

60

70

80

90

100

110

log10(M)

Rela

tive

In

du

ctio

n [

%]


Citoxlab

Envigo

RISE

BDS

DHT


107

Citoxlab

Envigo

RISE

BDS

run4

run10

run15

run2

run4

run9

run1

run16

run25

run1

run3

run5

[µM]

[mg/ml]

PRE

PRE

PRE

Pre

PRE

pre

PRE

PRE

PRE

PRE

PRE

PRE

7.69e-6

5e-10

0(0)

-1(0.1)0.1(0.1)

2.31e-5

1.5e-9

-0.1(0)

0.1(0.2)0.3(0.1)-0.1(0)

-0.9(0.2)-0.3(0.7)

0(0)

-0.3(0.1)0(0)

7.69e-5

5e-9

-0.1(0.1)

-1(0)

0(0)

2.31e-4

1.5e-8

0(0.1)-0.1(0.1)

0(0)

0.2(0.2)

-1(0.2)-0.1(1.3)

0(0)

-0.3(0)

0(0)

7.69e-4

5e-8

0(0.1)

-1(0)

0.1(0.1)

2.31e-3

1.5e-7

3.4(6)

0(0)

0.1(0.2)

1(1.5)

-1(0.1)-0.5(0.3)

0(0)

-0.3(0)

0(0)

7.69e-3

5e-7

0(0.1)

-1(0.1)0.1(0)

2.31e-2

1.5e-6

-0.1(0.2)

0(0.3)

0(0.2)0.5(0.2)-0.9(0.2)-0.6(0.1)-0.1(0.1)-0.3(0)

0(0)

7.69e-2

5e-6

-0.1(0)

-1(0)

0.1(0)

2.31e-1

1.5e-5

-0.2(0.2)0.1(0.1)-0.1(0.1)1.2(1.6)-1.1(0.2)-0.8(0.2)

0(0.1)-0.3(0)

0(0)

7.69e-1

5e-5

-0.1(0.1)

-1(0)

0.1(0)

2.31

1.5e-4

0(0.1)-0.1(0.4)0.1(0.1)3.8(0.1)

-1(0.3)-0.8(0)

-0.1(0.1)-0.3(0.1)0(0.1)

7.69

5e-4

0(0)

-0.9(0)

0.1(0.2)

23.08

1.5e-3

-0.2(0.1)-0.1(0.2)

0(0)

0.2(0.2)-1.2(0.1)-0.8(0.1)-0.1(0.1)-0.3(0)

0(0.1)

76.92

5e-3

-0.1(0)

-1(0)

0(0)

230.77

1.5e-2

2.2(0.6)-0.2(0.1)5.9(9.7)

0(0.1)

-1(0.2)-0.7(0.1)-0.1(0.1)-0.2(0)

0(0)

log 1

0(PC10)[mg/ml]

log 1

0(EC50)[mg/ml]


108

C.12 Test item 12

−11 −10 −9 −8 −7 −6 −5 −40

10

20

30

40

50

60

70

80

90

100

log10(M)

Rela

tive Induction [%

]TI−CIT2DQ, run 3, Citoxlab

−11 −10 −9 −8 −7 −6 −5 −40

10

20

30

40

50

60

70

80

90

100

log10(M)

Rela

tive Induction [%

]

TI−CIT2DQ, run 12, Citoxlab

−11 −10 −9 −8 −7 −6 −5 −40

10

20

30

40

50

60

70

80

90

100

log10(M)

Rela

tive Induction [%

]


−11 −10 −9 −8 −7 −6 −50

10

20

30

40

50

60

70

80

90

100

110

log10(M)

Re

lative

In

du

ctio

n [

%]

TI−ENV3FJ, run 1, Envigo

−11 −10 −9 −8 −7 −6 −50

10

20

30

40

50

60

70

80

90

100

110

log10(M)

Re

lative

In

du

ctio

n [

%]


−11 −10 −9 −8 −7 −6 −50

10

20

30

40

50

60

70

80

90

log10(M)

Re

lative

In

du

ctio

n [

%]


−11 −10 −9 −8 −7 −6 −50

10

20

30

40

50

60

70

80

90

100

log10(M)

Re

lative

In

du

ctio

n [

%]

TI−18SJ, run 2, RISE

−11 −10 −9 −8 −7 −6 −50

10

20

30

40

50

60

70

80

90

100

log10(M)

Re

lative

In

du

ctio

n [

%]


−11 −10 −9 −8 −7 −6 −50

10

20

30

40

50

60

70

80

90

100

log10(M)

Re

lative

In

du

ctio

n [

%]


−11 −10 −9 −8 −7 −6 −5 −40

10

20

30

40

50

60

70

80

90

100

log10(M)

Rela

tive Induction [%

]

TI−BDS2BU, run 2, BDS

−11 −10 −9 −8 −7 −6 −5 −40

10

20

30

40

50

60

70

80

90

100

log10(M)

Rela

tive Induction [%

]


−11 −10 −9 −8 −7 −6 −5 −4

10

20

30

40

50

60

70

80

90

100

log10(M)

Rela

tive Induction [%

]



109

−11 −10 −9 −8 −7 −6 −5 −40

10

20

30

40

50

60

70

80

90

100

log10(M)

Rela

tive Induction [%

]

TI−CIT2DQ, Citoxlab

run 3

run 12

run 15

DHT

−11 −10 −9 −8 −7 −6 −50

10

20

30

40

50

60

70

80

90

100

110

log10(M)

Rela

tive Induction [%

]

TI−ENV3FJ, Envigo

run 1

run 4

run 9

DHT

−11 −10 −9 −8 −7 −6 −50

10

20

30

40

50

60

70

80

90

100

log10(M)

Rela

tive Induction [%

]

TI−18SJ, RISE

run 2

run 5

run 25

DHT

−11 −10 −9 −8 −7 −6 −5 −40

10

20

30

40

50

60

70

80

90

100

log10(M)

Rela

tive Induction [%

]

TI−BDS2BU, BDS

run 2

run 3

run 5

DHT


−11 −10 −9 −8 −7 −6 −5 −40

10

20

30

40

50

60

70

80

90

100

110

log10(M)

Rela

tive

In

du

ctio

n [

%]


Citoxlab

Envigo

RISE

BDS

DHT


110

Citoxlab

Envigo

RISE

BDS

run3

run12

run15

run1

run4

run9

run2

run5

run25

run2

run3

run5

[µM]

[mg/ml]

PRE

PRE

PRE

PRE

PRE

pre

PRE

PRE

PRE

PRE

PRE

PRE

3.84e-6

1.5e-9

0.2(0.1)

0(0.3)

0(0.2)

0(0.3)

0(0.1)0.8(2.4)

1.28e-5

5e-9

0(0)

0(0.1)0(0)

0(0)

-0.2(0.1)0.1(0)

3.84e-5

1.5e-8

0(0.1)0.1(0.3)0.6(0.8)

0(0.1)-0.1(0.1)0.3(1.5)

1.28e-4

5e-8

2.5(0.2)

0(0)

0(0)

0(0.1)-0.2(0.1)0.1(0)

3.84e-4

1.5e-7

0.2(0.1)

0.1(0.7)0.2(0.1)

-0.1(0)

-0.3(0.1)0.6(2.2)

1.28e-3

5e-7

0.2(0)

0(0.1)0(0.1)

0(0.1)-0.3(0)

0.1(0)

3.84e-3

1.5e-6

0(0.3)0.1(0.2)

0(0.3)-0.1(0.1)-0.2(0.1)0.3(1.8)

1.28e-2

5e-6

0.1(0)

0(0)

0(0)

-0.1(0.1)-0.3(0)

0.1(0)

3.84e-2

1.5e-5

0(0.1)

0(0.2)

0(0.1)-0.1(0.1)-0.4(0.1)0.2(1.2)

1.28e-1

5e-5

0(0)

0.1(0)

0(0)

0(0.1)-0.3(0)

0.1(0)

3.84e-1

1.5e-4

0.1(0.1)

-0.1(0.2)0.1(0.3)

0(0)

-0.1(0.1)0.1(1.2)

1.28

5e-4

0(0)

0(0)

0(0.1)

0(0.1)-0.2(0)

0.1(0.1)

3.84

1.5e-3

0.2(0.2)

-0.1(0.2)

0(0.1)-0.1(0.1)-0.3(0.2)-0.2(1.1)

12.8

5e-3

0(0)

0(0)

0(0.1)

-0.1(0.1)-0.3(0)

0.1(0.1)

38.4

1.5e-2

0.1(0.1)

0.2(0.4)0.2(0.1)

-0.1(0.1)-0.4(0.2)-0.3(0.5)

128.01

5e-2

0(0.1)-0.1(0)

0(0.1)

-0.2(0.1)-0.3(0)

0(0)

log 1

0(PC10)[mg/ml]

log 1

0(EC50)[mg/ml]


111

C.13 Test item 13

−11 −10 −9 −8 −7

10

20

30

40

50

60

70

80

90

100

log10(M)

Re

lative

In

du

ctio

n [

%]

TI−CIT2TJ, run 8, Citoxlab

−11 −10 −9 −8 −70

10

20

30

40

50

60

70

80

90

100

log10(M)

Re

lative

In

du

ctio

n [

%]


−11 −10 −9 −8 −7

10

20

30

40

50

60

70

80

90

100

110

log10(M)

Re

lative

In

du

ctio

n [

%]


−11 −10 −9 −8 −7

10

20

30

40

50

60

70

80

90

100

110

log10(M)

Re

lative

In

du

ctio

n [

%]

TI−ENV3UJ, run 3, Envigo

−11 −10 −9 −8 −7

10

20

30

40

50

60

70

80

90

100

110

log10(M)

Re

lative

In

du

ctio

n [

%]


−11 −10 −9 −8 −7

10

20

30

40

50

60

70

80

90

100

log10(M)

Re

lative

In

du

ctio

n [

%]


−11 −10 −9 −8 −7

10

20

30

40

50

60

70

80

90

100

log10(M)

Re

lative

In

du

ctio

n [

%]

TI−9NY, run 13, RISE

−11 −10 −9 −8 −7

10

20

30

40

50

60

70

80

90

100

log10(M)

Re

lative

In

du

ctio

n [

%]


−11 −10 −9 −8 −7

10

20

30

40

50

60

70

80

90

100

log10(M)

Re

lative

In

du

ctio

n [

%]


−11 −10 −9 −8 −7

10

20

30

40

50

60

70

80

90

100

log10(M)

Re

lative

In

du

ctio

n [

%]

TI−BDS2VF, run 7, BDS

−11 −10 −9 −8 −7

10

20

30

40

50

60

70

80

90

100

log10(M)

Re

lative

In

du

ctio

n [

%]


−11 −10 −9 −8 −7

10

20

30

40

50

60

70

80

90

100

110

log10(M)

Re

lative

In

du

ctio

n [

%]



112

−11 −10 −9 −8 −70

10

20

30

40

50

60

70

80

90

100

110

log10(M)

Rela

tive Induction [%

]

TI−CIT2TJ, Citoxlab

run 8

run 13

run 16

DHT

−11 −10 −9 −8 −7

10

20

30

40

50

60

70

80

90

100

110

log10(M)

Rela

tive Induction [%

]

TI−ENV3UJ, Envigo

run 3

run 5

run 6

DHT

−11 −10 −9 −8 −7

10

20

30

40

50

60

70

80

90

100

log10(M)

Rela

tive Induction [%

]

TI−9NY, RISE

run 13

run 17

run 19

DHT

−11 −10 −9 −8 −7

10

20

30

40

50

60

70

80

90

100

log10(M)

Rela

tive Induction [%

]

TI−BDS2VF, BDS

run 7

run 8

run 10

DHT


−11 −10 −9 −8 −70

10

20

30

40

50

60

70

80

90

100

110

log10(M)

Rela

tive

In

du

ctio

n [

%]


Citoxlab

Envigo

RISE

BDS

DHT


113

Citoxlab

Envigo

RISE

BDS

run8

run13

run16

run3

run5

run6

run13

run17

run19

run7

run8

run10

[µM]

[mg/ml]

COM

COM

COM

COM

COM

COM

COM

COM

COM

COM

COM

COM

1.48e-5

4.5e-9

0.3(0.1)-0.5(0.1)

0.8(0.5)

0.3(0.2)

0.6(0.4)

0.8(0.1)

0.7(0.4)

0.3(0.1)

1.2(0)

1(0.1)

0.9(0.1)

1.1(0.1)

4.93e-5

1.5e-8

4.1(0.6)

2.5(0.2)

3.4(0.2)

3.1(0.3)

4.3(0.6)

5.3(1)

5.1(1)

5.3(1.6)

5.5(0.5)

5.5(0.2)

4.9(0.3)

8.6

(1)

1.48e-4

4.5e-8

28.1(0.7)

18.7(1.5)

17.2(1)

21(0.5)

25.6(3.2)

25.1(4.7)

27.4(3.1)

20.4(2.1)

28.3(1.5)

26.1(1.9)

24.5(1.1)

30.9(2.7)

4.93e-4

1.5e-7

57.6(0.8)

50.4(0.8)

52.3(4.1)

65.8(5.6)

67.3(9.7)

60.4(12.1)

51.5(2.1)

52.3(2.4)

63(5.2)

61.5(3.2)

59.8(3.7)

65.8(7.4)

1.48e-3

4.5e-7

82.5(2.2)

72.9(3.3)

75.2(4.2)

79.9(12)

85.5(3.9)

67.8(1.9)

77.4(2.2)

74.7(1)

84.9(8.1)

81.5(7)

85.4(1.9)

89(11.6)

4.93e-3

1.5e-6

87(2.5)

85.8(5.5)

85.7(4.2)

98.9(10.3)

97(11.5)

87.4(10.8)

82.5(3.6)

84.2(8.1)

96.6(5.7)

96.5(8.9)

91.8(5.5)

96.6(8.5)

1.48e-2

4.5e-6

89.6(1.9)

84.5(4.5)

87.7(2.2)

97.8(8.6)

98.1(13.7)

81.5(9.6)

91.6(2.8)

86.6(3.5)

96.9(3.2)

94.8(4)

97.8(4.2)

106.5(10.3)

4.93e-2

1.5e-5

88.7(2.8)

88.7(4.2)

91.1(4.4)

99.3(11.2)

99.1(9.4)

85.2(9.8)

91.1(2)

88.8(8.4)

96.7(1.5)

95.9(0.9)

99.6(5.3)

101.1(6)

log 1

0(PC10)[mg/ml]

-7.69

-7.55

-7.52

-7.54

-7.63

-7.65

-7.71

-7.62

-7.7

-7.68

-7.66

-7.78

log 1

0(EC50)[mg/ml]

-7.05

-6.91

-6.91

-6.98

-7.03

-7.07

-6.96

-6.95

-7.02

-7-6.97

-7.03


114

C.14 Test item 14

−11 −10 −9 −8 −7 −6 −50

10

20

30

40

50

60

70

80

90

100

log10(M)

Re

lative

In

du

ctio

n [

%]

TI−CIT2NN, run 3, Citoxlab

−11 −10 −9 −8 −7 −6 −50

10

20

30

40

50

60

70

80

90

100

log10(M)

Rela

tive Induction [%

]


−11 −10 −9 −8 −7 −6 −50

10

20

30

40

50

60

70

80

90

100

log10(M)

Re

lative

In

du

ctio

n [

%]


−11 −10 −9 −8 −7 −6 −50

10

20

30

40

50

60

70

80

90

100

110

log10(M)

Re

lative

In

du

ctio

n [

%]

TI−ENV3GU, run 1, Envigo

−11 −10 −9 −8 −7 −6 −50

10

20

30

40

50

60

70

80

90

100

110

log10(M)

Re

lative

In

du

ctio

n [

%]


−11 −10 −9 −8 −7 −6 −50

10

20

30

40

50

60

70

80

90

log10(M)

Re

lative

In

du

ctio

n [

%]


−11 −10 −9 −8 −7 −6 −50

10

20

30

40

50

60

70

80

90

100

log10(M)

Re

lative

In

du

ctio

n [

%]

TI−22RU, run 3, RISE

−11 −10 −9 −8 −7 −6 −50

10

20

30

40

50

60

70

80

90

100

log10(M)

Re

lative

In

du

ctio

n [

%]


−11 −10 −9 −8 −7 −6 −50

10

20

30

40

50

60

70

80

90

100

log10(M)

Re

lative

In

du

ctio

n [

%]


−11 −10 −9 −8 −7 −6 −50

10

20

30

40

50

60

70

80

90

100

log10(M)

Re

lative

In

du

ctio

n [

%]

TI−BDS2AJ, run 1, BDS

−11 −10 −9 −8 −7 −6 −50

10

20

30

40

50

60

70

80

90

100

log10(M)

Re

lative

In

du

ctio

n [

%]


−11 −10 −9 −8 −7 −6 −50

10

20

30

40

50

60

70

80

90

100

log10(M)

Re

lative

In

du

ctio

n [

%]



115

−11 −10 −9 −8 −7 −6 −50

10

20

30

40

50

60

70

80

90

100

log10(M)

Rela

tive Induction [%

]

TI−CIT2NN, Citoxlab

run 3

run 11

run 15

DHT

−11 −10 −9 −8 −7 −6 −50

10

20

30

40

50

60

70

80

90

100

110

log10(M)

Rela

tive Induction [%

]

TI−ENV3GU, Envigo

run 1

run 4

run 9

DHT

−11 −10 −9 −8 −7 −6 −50

10

20

30

40

50

60

70

80

90

100

log10(M)

Rela

tive Induction [%

]

TI−22RU, RISE

run 3

run 14

run 21

DHT

−11 −10 −9 −8 −7 −6 −50

10

20

30

40

50

60

70

80

90

100

log10(M)

Rela

tive Induction [%

]

TI−BDS2AJ, BDS

run 1

run 3

run 5

DHT


−11 −10 −9 −8 −7 −6 −50

10

20

30

40

50

60

70

80

90

100

110

log10(M)

Rela

tive

In

du

ctio

n [

%]


Citoxlab

Envigo

RISE

BDS

DHT


116

Citoxlab

Envigo

RISE

BDS

run3

run11

run15

run1

run4

run9

run3

run14

run21

run1

run3

run5

[µM]

[mg/ml]

PRE

PRE

PRE

PRE

PRE

pre

PRE

PRE

PRE

PRE

PRE

PRE

1.57e-6

4.5e-10

0(0)

1.75e-6

5e-10

0(0.1)-0.2(0.1)-0.3(0)

5.24e-6

1.5e-9

0(0)

0(0)

0(0.2)-0.4(0.3)-0.1(0.1)

0.1(0.1)-0.2(0.1)-0.1(0)

1.57e-5

4.5e-9

0(0)

1.75e-5

5e-9

-0.1(0.1)-0.3(0.2)0.5(0.1)

5.24e-5

1.5e-8

0(0)

13.2(1)

-0.1(0.1)

0(0.2)

0(0.1)

0(0)

-0.2(0.1)

0(0.1)

1.57e-4

4.5e-8

0(0)

1.75e-4

5e-8

0.1(0.2)-0.3(0.1)-0.2(0.2)

5.24e-4

1.5e-7

0(0)

0(0.1)

0.1(0.1)

0(0.1)0.1(0.1)

0(0)

-0.3(0)

0(0.1)

1.57e-3

4.5e-7

0(0)

1.75e-3

5e-7

-0.2(0.2)-0.1(0.3)0.1(0)

5.24e-3

1.5e-6

0.1(0)

0(0.1)

-0.1(0)

-0.2(0.3)0.1(0.2)

-0.1(0)

-0.3(0)

0(0)

1.57e-2

4.5e-6

0(0)

1.75e-2

5e-6

-0.1(0.2)-0.5(0.1)-0.3(0.1)

5.24e-2

1.5e-5

0(0)

1.8(0.1)

-0.1(0.1)0.2(0.2)-0.1(0.2)

0(0.1)-0.3(0)

0.1(0)

1.57e-1

4.5e-5

0(0)

1.75e-1

5e-5

-0.2(0.1)-0.1(0.1)-0.4(0.1)

5.24e-1

1.5e-4

0(0.1)

0(0)

0(0.1)0.2(0.1)

0(0.1)

0(0)

-0.2(0)

0(0)

1.57

4.5e-4

0(0)

1.75

5e-4

-0.2(0.1)-0.5(0)

-0.3(0)

5.24

1.5e-3

0.1(0)

0.1(0.1)

0.3(0.1)

0(0.2)-0.1(0.1)

0.1(0.1)-0.1(0.1)0.1(0)

15.73

4.5e-3

0.2(0)

17.48

5e-3

0.3(0.2)-0.3(0.1)

0(0.1)

52.43

1.5e-2

0.6(0)

cyt/excl

1(0.1)0.6(0.1)0.7(0.4)

0.8(0.1)0.3(0.1)0.5(0.1)

log 1

0(PC10)[mg/ml]

-8.52

log 1

0(EC50)[mg/ml]

na


117

C.15 Test item 15

−11 −10 −9 −8 −7 −6 −5 −40

10

20

30

40

50

60

70

80

90

100

log10(M)

Rela

tive Induction [%

]TI−CIT2JB, run 3, Citoxlab

−11 −10 −9 −8 −7 −6 −50

10

20

30

40

50

60

70

80

90

100

log10(M)

Rela

tive Induction [%

]

TI−CIT2JB, run 14, Citoxlab

−11 −10 −9 −8 −7 −6 −50

10

20

30

40

50

60

70

80

90

log10(M)

Re

lative

In

du

ctio

n [

%]


−11 −10 −9 −8 −7 −6 −5 −40

10

20

30

40

50

60

70

80

90

100

110

log10(M)

Rela

tive Induction [%

]

TI−ENV3BH, run 1, Envigo

−11 −10 −9 −8 −7 −6 −50

10

20

30

40

50

60

70

80

90

100

110

log10(M)

Re

lative

In

du

ctio

n [

%]


−11 −10 −9 −8 −7 −6 −50

10

20

30

40

50

60

70

80

90

log10(M)

Re

lative

In

du

ctio

n [

%]


−11 −10 −9 −8 −7 −6 −5 −40

10

20

30

40

50

60

70

80

90

100

log10(M)

Rela

tive Induction [%

]

TI−28ZZ, run 5, RISE

−11 −10 −9 −8 −7 −6 −50

10

20

30

40

50

60

70

80

90

100

log10(M)

Re

lative

In

du

ctio

n [

%]


−11 −10 −9 −8 −7 −6 −50

10

20

30

40

50

60

70

80

90

100

log10(M)

Re

lative

In

du

ctio

n [

%]


−11 −10 −9 −8 −7 −6 −5 −40

10

20

30

40

50

60

70

80

90

100

log10(M)

Re

lative

In

du

ctio

n [

%]

TI−BDS2AN, run 2, BDS

−11 −10 −9 −8 −7 −6 −5 −40

10

20

30

40

50

60

70

80

90

100

log10(M)

Re

lative

In

du

ctio

n [

%]


−11 −10 −9 −8 −7 −6 −5 −40

10

20

30

40

50

60

70

80

90

100

log10(M)

Re

lative

In

du

ctio

n [

%]



118

−11 −10 −9 −8 −7 −6 −5 −40

10

20

30

40

50

60

70

80

90

100

log10(M)

Rela

tive Induction [%

]

TI−CIT2JB, Citoxlab

run 3

run 14

run 18

DHT

−11 −10 −9 −8 −7 −6 −5 −40

10

20

30

40

50

60

70

80

90

100

110

log10(M)

Rela

tive Induction [%

]

TI−ENV3BH, Envigo

run 1

run 4

run 9

DHT

−11 −10 −9 −8 −7 −6 −5 −40

10

20

30

40

50

60

70

80

90

100

log10(M)

Rela

tive Induction [%

]

TI−28ZZ, RISE

run 5

run 14

run 23

DHT

−11 −10 −9 −8 −7 −6 −5 −40

10

20

30

40

50

60

70

80

90

100

log10(M)

Rela

tive Induction [%

]

TI−BDS2AN, BDS

run 2

run 4

run 6

DHT


−11 −10 −9 −8 −7 −6 −5 −40

10

20

30

40

50

60

70

80

90

100

110

log10(M)

Re

lative

In

ductio

n [

%]


Citoxlab

Envigo

RISE

BDS

DHT


119

Citoxlab

Envigo

RISE

BDS

run3

run14

run18

run1

run4

run9

run5

run14

run23

run2

run4

run6

[µM]

[mg/ml]

PRE

PRE

PRE

PRE

PRE

pre

PRE

PRE

PRE

PRE

PRE

PRE

1.19e-6

4.5e-10

0(0.1)

1.33e-6

5e-10

0.1(0.3)

0(0.1)

-0.4(0.1)0.4(0.7)

3.98e-6

1.5e-9

-1.2(0)

1.19e-5

4.5e-9

0(0)

1.33e-5

5e-9

0(0)

0.1(0.2)0.3(0.1)0.1(0.2)-0.1(0.1)-0.1(0)

0.3(1)

0(0)

-0.2(0.1)

0(0.1)

3.98e-5

1.5e-8

-1.2(0)

1.19e-4

4.5e-8

0.1(0.1)

1.33e-4

5e-8

0(0)

0.1(0.1)-0.1(0.1)0.2(0.1)-0.1(0.1)-0.2(0.1)0.3(0.8)

0(0.1)-0.3(0)

0(0)

3.98e-4

1.5e-7

-1.2(0)

1.19e-3

4.5e-7

0(0.2)

1.33e-3

5e-7

0(0)

-0.1(0.2)

0(0.1)0.1(0.2)-0.1(0.1)-0.3(0.2)0.3(0.8)

0(0)

-0.2(0.1)

0(0)

3.98e-3

1.5e-6

-1.1(0)

1.19e-2

4.5e-6

0(0.1)

1.33e-2

5e-6

42.9(4.7)

0(0.3)

0(0.1)0.1(0.2)-0.3(0.1)-0.4(0.1)0.3(0.9)

0(0)

-0.2(0.1)

0(0.1)

3.98e-2

1.5e-5

-1.1(0)

1.19e-1

4.5e-5

0(0.1)

1.33e-1

5e-5

0.2(0.1)

0.1(0.2)

0(0.1)

0(0.1)-0.2(0.1)-0.5(0.2)0.2(0.9)

0(0)

-0.2(0)

0(0)

3.98e-1

1.5e-4

-1.2(0)

1.19

4.5e-4

0(0.2)

1.33

5e-4

0.1(0.1)

1.3(0.2)

0(0.1)-0.1(0.2)-0.3(0.2)-0.4(0.2)

0(0.9)

0(0.1)-0.2(0)

0(0)

3.98

1.5e-3

-1.3(0)

11.95

4.5e-3

-0.3(0.1)

13.27

5e-3

-0.2(0)

-0.4(0.1)-0.2(0.2)-0.2(0.2)-0.6(0.2)-0.5(0)

-0.3(0.6)-0.2(0)

-0.3(0.1)-0.1(0)

39.82

1.5e-2

cyt/excl

132.73

5e-2

cyt/excl

cyt/excl

cyt/excl

-0.8(0.1)-0.8(0)

-0.8(0)

log 1

0(PC10)[mg/ml]

-6.09

log 1

0(EC50)[mg/ml]

na


120

C.16 Test item 16

−11 −10 −9 −8 −7 −6 −5

10

20

30

40

50

60

70

80

90

100

110

log10(M)

Re

lative

In

du

ctio

n [

%]

TI−CIT2YW, run 16, Citoxlab

−11 −10 −9 −8 −7 −6 −5

10

20

30

40

50

60

70

80

90

log10(M)

Re

lative

In

du

ctio

n [

%]


−11 −10 −9 −8 −7 −6 −5

10

20

30

40

50

60

70

80

90

100

log10(M)

Re

lative

In

du

ctio

n [

%]


−11 −10 −9 −8 −7

10

20

30

40

50

60

70

80

90

100

110

log10(M)

Re

lative

In

du

ctio

n [

%]

TI−ENV3DX, run 3, Envigo

−11 −10 −9 −8 −70

10

20

30

40

50

60

70

80

90

100

log10(M)

Re

lative

In

du

ctio

n [

%]


−11 −10 −9 −8 −7 −6

10

20

30

40

50

60

70

80

90

100

log10(M)

Re

lative

In

du

ctio

n [

%]


−11 −10 −9 −8 −7 −6 −5

10

20

30

40

50

60

70

80

90

100

log10(M)

Re

lative

In

du

ctio

n [

%]

TI−3FA, run 4, RISE

−11 −10 −9 −8 −7 −6 −5

10

20

30

40

50

60

70

80

90

100

log10(M)

Re

lative

In

du

ctio

n [

%]


−11 −10 −9 −8 −7 −6 −5

10

20

30

40

50

60

70

80

90

100

log10(M)

Re

lative

In

du

ctio

n [

%]


−11 −10 −9 −8 −7

10

20

30

40

50

60

70

80

90

100

log10(M)

Re

lative

In

du

ctio

n [

%]

TI−BDS2BG, run 7, BDS

−11 −10 −9 −8 −7

10

20

30

40

50

60

70

80

90

100

log10(M)

Re

lative

In

du

ctio

n [

%]


−11 −10 −9 −8 −7

10

20

30

40

50

60

70

80

90

100

log10(M)

Re

lative

In

du

ctio

n [

%]



121

−11 −10 −9 −8 −7 −6 −5

10

20

30

40

50

60

70

80

90

100

110

log10(M)

Rela

tive Induction [%

]

TI−CIT2YW, Citoxlab

run 16

run 17

run 19

DHT

−11 −10 −9 −8 −7 −60

10

20

30

40

50

60

70

80

90

100

110

log10(M)

Rela

tive Induction [%

]

TI−ENV3DX, Envigo

run 3

run 5

run 8

DHT

−11 −10 −9 −8 −7 −6 −5

10

20

30

40

50

60

70

80

90

100

log10(M)

Rela

tive Induction [%

]

TI−3FA, RISE

run 4

run 7

run 13

DHT

−11 −10 −9 −8 −7

10

20

30

40

50

60

70

80

90

100

log10(M)

Rela

tive Induction [%

]

TI−BDS2BG, BDS

run 7

run 8

run 10

DHT


−11 −10 −9 −8 −7 −6 −50

10

20

30

40

50

60

70

80

90

100

110

log10(M)

Rela

tive

In

du

ctio

n [

%]


Citoxlab

Envigo

RISE

BDS

DHT


122

Citoxlab

Envigo

RISE

BDS

run16

run17

run19

run3

run5

run8

run4

run7

run13

run7

run8

run10

[µM]

[mg/ml]

COM

COM

COM

COM

COM

COM

COM

COM

COM

COM

COM

COM

1.34e-4

4.5e-8

0.5(0.1)

0(0.3)

0.5(0.4)

0.2(0.1)

0.2(0.1)

0.2(0.1)

4.46e-4

1.5e-7

1(0.5)

0.8(0.1)

0.6(0.2)

0.7(0.1)

0.4(0.2)

0.8(0.1)

0.9(0.1)

1.3(0.1)

5.71e-4

1.92e-7

0.8(0.3)

11.5(0.5)

0.4(0)

1.34e-3

4.5e-7

4.6(0.9)

4.3(0.5)

4.8(0.7)

4(0)

4.1(0.2)

5.2(0.5)

6.2(0.9)

1.49e-3

5e-7

3.9(0.2)

3.1(0.3)

2.85e-3

9.6e-7

5.1(2.4)

10.1(3)

4.8(0.6)

4.46e-3

1.5e-6

23.4(3)

20.9(3.5)

16.7(1.6)

17.5(2.2)

13.5(0.5)

13.9(1.9)

15(0.7)

18.1(0.5)

23.1(2)

1.34e-2

4.5e-6

44.8(6.5)

36.5(1.2)

37(0.9)

35.6(0.6)

36.2(0.1)

38.2(2.1)

43.3(3.2)

1.43e-2

4.8e-6

22.1(13.3)

31.2(1)

23.8(1.6)

1.49e-2

5e-6

31.2(1)

31.2(1.2)

30.4(1)

4.46e-2

1.5e-5

56.9(8.7)

51.2(4.3)

52.3(0.6)

45.3(2.3)

43.9(1.5)

42.8(2.9)

52.9(2)

54.8(0.4)

60.3(1.5)

7.13e-2

2.4e-5

47(21.1)

47.8(1)

41.9(2.3)

1.34e-1

4.5e-5

65.7(5.3)

58.3(2.2)

59.1(4.2)

52.6(2.3)

60.9(2.2)

60.5(1.5)

66.3(5.9)

1.49e-1

5e-5

49.3(0.9)

49.1(1.9)

49.7(3.4)

3.57e-1

1.2e-4

53(18)

55.6(1.5)

50.4(1.1)

4.46e-1

1.5e-4

66(7.6)

61(8.1)

65.9(1.4)

55.6(4.2)

52.7(1.2)

53.8(3)

62.9(0.4)

64.9(1.9)

64.5(5.5)

1.34

4.5e-4

67.7(8.6)

1.49

5e-4

56.6(2)

55.9(1.3)

54.8(2.3)

1.78

6e-4

58.8(16.6)

57.2(3.1)

53.1(1.7)

4.46

1.5e-3

74.9(3.9)

59.2(2.4)

61.4(2.3)

61.9(2.7)

8.92

3e-3

70.2(8.2)

64.5(2.8)

62.8(2.7)

14.86

5e-3

70.1(2.8)

69.2(2.7)

69(1.1)

44.59

1.5e-2

74.9(21.7)

74.7(0.7)

68.4(3.2)

log 1

0(PC10)[mg/ml]

-5.75

-6.02

-5.8

-6.15

-6.13

-6.01

-5.96

-5.96

-5.97

-5.99

-6.1

-6.19

log 1

0(EC50)[mg/ml]

-4.82

-5.03

-4.89

-5.59

-5.51

-5.31

-5.35

-5.26

-5.24

-5.43

-5.47

-5.59


123

C.17 Test item 17

−11 −10 −9 −8 −7 −60

10

20

30

40

50

60

70

80

90

100

log10(M)

Re

lative

In

du

ctio

n [

%]

TI−CIT2ML, run 8, Citoxlab

−11 −10 −9 −8 −7 −60

10

20

30

40

50

60

70

80

90

100

log10(M)

Re

lative

In

du

ctio

n [

%]


−11 −10 −9 −8 −7 −60

10

20

30

40

50

60

70

80

90

log10(M)

Re

lative

In

du

ctio

n [

%]


−11 −10 −9 −8 −7 −6 −5

10

20

30

40

50

60

70

80

90

100

110

log10(M)

Re

lative

In

du

ctio

n [

%]

TI−ENV3PU, run 3, Envigo

−11 −10 −9 −8 −7 −6 −5

10

20

30

40

50

60

70

80

90

100

log10(M)

Re

lative

In

du

ctio

n [

%]


−11 −10 −9 −8 −7 −60

10

20

30

40

50

60

70

80

90

100

log10(M)

Re

lative

In

du

ctio

n [

%]


−11 −10 −9 −8 −7 −60

10

20

30

40

50

60

70

80

90

100

log10(M)

Re

lative

In

du

ctio

n [

%]

TI−32BL, run 15, RISE

−11 −10 −9 −8 −7 −60

10

20

30

40

50

60

70

80

90

100

log10(M)

Rela

tive Induction [%

]


−11 −10 −9 −8 −7 −6

10

20

30

40

50

60

70

80

90

100

log10(M)

Re

lative

In

du

ctio

n [

%]


−11 −10 −9 −8 −7 −6 −5

10

20

30

40

50

60

70

80

90

100

log10(M)

Re

lative

In

du

ctio

n [

%]

TI−BDS2UE, run 7, BDS

−11 −10 −9 −8 −7 −6 −5

10

20

30

40

50

60

70

80

90

100

log10(M)

Re

lative

In

du

ctio

n [

%]


−11 −10 −9 −8 −7 −6 −5

10

20

30

40

50

60

70

80

90

100

log10(M)

Re

lative

In

du

ctio

n [

%]



124

−11 −10 −9 −8 −7 −60

10

20

30

40

50

60

70

80

90

100

log10(M)

Rela

tive Induction [%

]

TI−CIT2ML, Citoxlab

run 8

run 13

run 17

DHT

−11 −10 −9 −8 −7 −6 −5

10

20

30

40

50

60

70

80

90

100

110

log10(M)

Rela

tive Induction [%

]

TI−ENV3PU, Envigo

run 3

run 5

run 8

DHT

−11 −10 −9 −8 −7 −60

10

20

30

40

50

60

70

80

90

100

log10(M)

Rela

tive Induction [%

]

TI−32BL, RISE

run 15

run 19

run 22

DHT

−11 −10 −9 −8 −7 −6 −5

10

20

30

40

50

60

70

80

90

100

log10(M)

Rela

tive Induction [%

]

TI−BDS2UE, BDS

run 7

run 8

run 10

DHT


−11 −10 −9 −8 −7 −6 −50

10

20

30

40

50

60

70

80

90

100

110

log10(M)

Rela

tive

In

du

ctio

n [

%]


Citoxlab

Envigo

RISE

BDS

DHT


125

Citoxlab

Envigo

RISE

BDS

run8

run13

run17

run3

run5

run8

run15

run19

run22

run7

run8

run10

[µM]

[mg/ml]

COM

COM

COM

COM

COM

COM

COM

COM

COM

COM

COM

COM

1.65e-3

4.5e-7

-0.2(0)

-0.8(0.1)

0.8(0.1)

0.3(0.4)-0.6(0.2)

0.5(0.1)

0.5(0.6)

4.96e-3

1.35e-6

1.7(0.2)

1.4(0.5)

2.1(0.1)

1.8(0)

2(0.1)

5.51e-3

1.5e-6

2.6(0.4)

0(0.2)

1.2(0)

1(0.3)

0.9(0.1)

1.8(0.3)

1.9(0.6)

1.65e-2

4.5e-6

2.5(0.2)

1.5(0.1)

2.7(0.1)

4.9(0.8)

4.1(0.2)

2.5(0.3)

2.8(0.3)

3.5(0.5)

3.8(0.4)

5.2(0.9)

4.1(0.3)

4.4(0.4)

4.96e-2

1.35e-5

7.2(1.7)

5.7(0.7)

7.9(0.7)

6.2(0.3)

7.5(0.5)

5.51e-2

1.5e-5

4(0.2)

3.2(0.1)

4.6(0.5)

4.1(0.3)

4.2(0.5)

4.2(0.7)

5.5(0.7)

1.65e-1

4.5e-5

5.5(0.3)

4.7(0.3)

5.5(0.2)

8.8(1.7)

6.9(0.8)

5.7(1)

6(0.8)

5.7(0.6)

6.4(0.8)

9.8(1.3)

7.3(0.7)

7.7(0.3)

4.96e-1

1.35e-4

10.5(3)

9.5(0.5)

11.7(0.4)

9.3(0.2)

10.2(1.1)

5.51e-1

1.5e-4

7.3(0.3)

6.9(1)

5.2(4.6)

8.6(0.3)

9.7(0.3)

7.9(0.2)

8.4(0.5)

1.65

4.5e-4

12.7(0.9)

10.8(0.5)

12.5(0.8)

17.5(1.6)

17.1(1.8)

13.7(0.1)

13.8(1.2)

12.8(1.3)

12.7(1.2)

18.6(0.8)

14.9(1.1)

17(1.6)

4.96

1.35e-3

31.5(3.8)

26.7(5.4)

30.6(3.2)

23.8(0.7)

28.4(1.2)

5.51

1.5e-3

23(2.3)

17.4(1.5)

19.4(0.7)

25.9(0.5)

26(3.9)

cyt/excl

22.6(1)

16.52

4.5e-3

30.8(1.2)

25.7(3.4)

37(1.2)

31(0.4)

38.1(1.9)

interpvalue(x)

9.7(0.2)

log 1

0(PC10)[mg/ml]

-3.54

-3.42

-3.48

-3.97

-3.82

-3.66

-3.78

-3.57

-3.6

-4.27

-3.77

-3.89

log 1

0(EC50)[mg/ml]

nana

nana

-3.39

nana

nana

nana

na


126

C.18 Test item 18

−11 −10 −9 −8 −7 −6 −50

10

20

30

40

50

60

70

80

90

100

log10(M)

Re

lative

In

du

ctio

n [

%]

TI−CIT2PY, run 4, Citoxlab

−11 −10 −9 −8 −7 −6 −50

10

20

30

40

50

60

70

80

90

100

log10(M)

Re

lative

In

du

ctio

n [

%]


−11 −10 −9 −8 −7 −6 −50

10

20

30

40

50

60

70

80

90

100

log10(M)

Re

lative

In

du

ctio

n [

%]


−11 −10 −9 −8 −7 −6 −5 −40

10

20

30

40

50

60

70

80

90

100

110

log10(M)

Re

lative

In

du

ctio

n [

%]

TI−ENV3KU, run 1, Envigo

−11 −10 −9 −8 −7 −6 −5 −40

10

20

30

40

50

60

70

80

90

100

110

log10(M)

Re

lative

In

du

ctio

n [

%]


−11 −10 −9 −8 −7 −6 −5 −40

10

20

30

40

50

60

70

80

90

log10(M)

Re

lative

In

du

ctio

n [

%]


−12 −11 −10 −9 −8 −7 −60

10

20

30

40

50

60

70

80

90

100

log10(M)

Re

lative

In

du

ctio

n [

%]

TI−30QT, run 5, RISE

−12 −11 −10 −9 −8 −7 −60

10

20

30

40

50

60

70

80

90

100

log10(M)

Re

lative

In

du

ctio

n [

%]


−12 −11 −10 −9 −8 −7 −60

10

20

30

40

50

60

70

80

90

100

log10(M)

Re

lative

In

du

ctio

n [

%]


−11 −10 −9 −8 −7 −6 −50

10

20

30

40

50

60

70

80

90

100

log10(M)

Re

lative

In

du

ctio

n [

%]

TI−BDS2CM, run 2, BDS

−11 −10 −9 −8 −7 −6 −50

10

20

30

40

50

60

70

80

90

100

log10(M)

Re

lative

In

du

ctio

n [

%]


−11 −10 −9 −8 −7 −6 −50

10

20

30

40

50

60

70

80

90

100

log10(M)

Re

lative

In

du

ctio

n [

%]



127

−11 −10 −9 −8 −7 −6 −50

10

20

30

40

50

60

70

80

90

100

log10(M)

Rela

tive Induction [%

]

TI−CIT2PY, Citoxlab

run 4

run 11

run 15

DHT

−11 −10 −9 −8 −7 −6 −5 −40

10

20

30

40

50

60

70

80

90

100

110

log10(M)

Rela

tive Induction [%

]

TI−ENV3KU, Envigo

run 1

run 4

run 9

DHT

−12 −11 −10 −9 −8 −7 −60

10

20

30

40

50

60

70

80

90

100

log10(M)

Rela

tive Induction [%

]

TI−30QT, RISE

run 5

run 16

run 23

DHT

−11 −10 −9 −8 −7 −6 −50

10

20

30

40

50

60

70

80

90

100

log10(M)

Rela

tive Induction [%

]

TI−BDS2CM, BDS

run 2

run 3

run 5

DHT


−12 −11 −10 −9 −8 −7 −6 −5 −40

10

20

30

40

50

60

70

80

90

100

110

log10(M)

Rela

tive

In

du

ctio

n [

%]


Citoxlab

Envigo

RISE

BDS

DHT


128

Citoxlab

Envigo

RISE

BDS

run4

run11

run15

run1

run4

run9

run5

run16

run23

run2

run3

run5

[µM]

[mg/ml]

PRE

PRE

PRE

PRE

PRE

pre

PRE

PRE

PRE

PRE

PRE

PRE

4.8e-7

1.5e-10

-0.1(0.2)-0.4(0.1)-0.5(0.2)

4.8e-6

1.5e-9

0(0)

0(0)

0.1(0)

-0.1(0.2)-0.5(0.1)-0.5(0.2)

0(0.1)-0.4(0)

0(0)

1.6e-5

5e-9

0(0.3)-0.2(0.1)

0(0)

4.8e-5

1.5e-8

0(0)

0(0)

0.1(0.1)

-0.1(0.1)-0.4(0.2)-0.3(0.4)

0(0)

-0.4(0)

-0.1(0)

1.6e-4

5e-8

-0.1(0.1)0.1(0.1)0.1(0)

4.8e-4

1.5e-7

0(0)0.1(0)

0.1(0.1)

-0.4(0.1)-0.4(0.2)-0.5(0.2)

0(0.1)-0.3(0)

0(0)

1.6e-3

5e-7

0(0.1)

0(0.1)-0.2(0.1)

4.8e-3

1.5e-6

0(0)

0(0)

0(0.1)

-0.1(0.2)-0.3(0.2)-0.4(0.2)

0(0)

-0.4(0)

0(0)

1.6e-2

5e-6

0(0.1)-0.2(0.2)-0.1(0.3)

4.8e-2

1.5e-5

0(0)2.1(0.1)0.1(0)

-0.2(0.1)-0.5(0.2)-0.8(0.1)

0(0)

-0.4(0.1)0.1(0)

1.6e-1

5e-5

0.1(0.2)0.1(0.1)-0.2(0)

4.8e-1

1.5e-4

0(0)

0(0)

0(0)

-0.2(0.1)-0.4(0.2)-0.6(0.2)0.1(0.1)

-0.3(0.1)0.1(0)

1.6

5e-4

0.2(0.1)

0(0.3)

0(0.1)

4.8

1.5e-3

0(0)

0(0)

0(0)

-0.4(0.3)-0.4(0)

-0.6(0.1)0.1(0)

-0.2(0.1)0.1(0)

16.01

5e-3

0.3(0.1)-0.2(0.3)

0(0)

48.02

1.5e-2

-0.1(0)-0.2(0)

-0.2(0)

0(0)

-0.1(0)

0.2(0)

160.05

5e-2

0.1(0.1)-0.3(0)

0(0.1)

log 1

0(PC10)[mg/ml]

log 1

0(EC50)[mg/ml]


129

C.19 Test item 19

−11 −10 −9 −8 −7 −6 −5 −40

10

20

30

40

50

60

70

80

90

100

log10(M)

Re

lative

In

du

ctio

n [

%]

TI−CIT2HZ, run 3, Citoxlab

−11 −10 −9 −8 −7 −6 −5 −40

10

20

30

40

50

60

70

80

90

100

log10(M)

Re

lative

In

du

ctio

n [

%]


−11 −10 −9 −8 −7 −6 −5 −40

10

20

30

40

50

60

70

80

90

100

log10(M)

Re

lative

In

du

ctio

n [

%]


−11 −10 −9 −8 −7 −6 −5 −40

10

20

30

40

50

60

70

80

90

100

110

log10(M)

Re

lative

In

du

ctio

n [

%]

TI−ENV3CK, run 4, Envigo

−11 −10 −9 −8 −7 −6 −5 −40

10

20

30

40

50

60

70

80

90

100

log10(M)

Re

lative

In

du

ctio

n [

%]


−11 −10 −9 −8 −7 −6 −5 −40

10

20

30

40

50

60

70

80

90

log10(M)

Re

lative

In

du

ctio

n [

%]


−11 −10 −9 −8 −7 −6 −5 −40

10

20

30

40

50

60

70

80

90

100

log10(M)

Re

lative

In

du

ctio

n [

%]

TI−20WZ, run 3, RISE

−11 −10 −9 −8 −7 −6 −5 −40

10

20

30

40

50

60

70

80

90

100

log10(M)

Re

lative

In

du

ctio

n [

%]


−11 −10 −9 −8 −7 −6 −5 −40

10

20

30

40

50

60

70

80

90

100

log10(M)

Re

lative

In

du

ctio

n [

%]


−11 −10 −9 −8 −7 −6 −5 −40

10

20

30

40

50

60

70

80

90

100

log10(M)

Re

lative

In

du

ctio

n [

%]

TI−BDS2NZ, run 1, BDS

−11 −10 −9 −8 −7 −6 −5 −40

10

20

30

40

50

60

70

80

90

100

log10(M)

Re

lative

In

du

ctio

n [

%]


−11 −10 −9 −8 −7 −6 −5 −40

10

20

30

40

50

60

70

80

90

100

log10(M)

Re

lative

In

du

ctio

n [

%]



130

−11 −10 −9 −8 −7 −6 −5 −40

10

20

30

40

50

60

70

80

90

100

log10(M)

Rela

tive Induction [%

]


run 3

run 12

run 15

DHT

−11 −10 −9 −8 −7 −6 −5 −40

10

20

30

40

50

60

70

80

90

100

110

log10(M)

Rela

tive Induction [%

]

TI−ENV3CK, Envigo

run 4

run 7

run 9

DHT

−11 −10 −9 −8 −7 −6 −5 −40

10

20

30

40

50

60

70

80

90

100

log10(M)

Rela

tive Induction [%

]

TI−20WZ, RISE

run 3

run 14

run 18

DHT

−11 −10 −9 −8 −7 −6 −5 −40

10

20

30

40

50

60

70

80

90

100

log10(M)

Rela

tive Induction [%

]

TI−BDS2NZ, BDS

run 1

run 3

run 5

DHT


−11 −10 −9 −8 −7 −6 −5 −40

10

20

30

40

50

60

70

80

90

100

110

log10(M)

Rela

tive

In

du

ctio

n [

%]


Citoxlab

Envigo

RISE

BDS

DHT


131

Citoxlab

Envigo

RISE

BDS

run3

run12

run15

run4

run7

run9

run3

run14

run18

run1

run3

run5

[µM]

[mg/ml]

PRE

PRE

PRE

PRE

PRE

pre

PRE

PRE

PRE

PRE

PRE

PRE

2.94e-5

5e-9

0(0)-0.1(0)

0(0)

0.1(0.4)0.2(0.1)

-0.1(0.1)-0.1(0.1)

0(0.2)0.1(0.3)0.1(0.1)

-0.3(0.1)

0(0)

2.94e-4

5e-8

0.3(0)

-0.1(0)

0(0.1)-0.1(0.2)0.2(0.1)

0(0.1)

0(0.3)

0(0.1)0.1(0.3)0.1(0)

-0.3(0)

0(0.1)

2.94e-3

5e-7

0.2(0)

-0.1(0.1)0.1(0.1)

-0.1(0.5)0.1(0.3)

0(0.1)

0(0.2)-0.3(0.2)

0(0.5)0.1(0.1)

-0.3(0)

0.1(0)

2.94e-2

5e-6

0.1(0)

1(0.1)0.1(0.1)

-0.1(0)

0(0.2)-0.2(0.2)-0.1(0.2)-0.3(0.1)

0(0.2)

0(0.1)-0.3(0)

0(0.1)

2.94e-1

5e-5

0.1(0)

0.9(0.1)0.1(0.1)

-0.2(0.1)

0(0.2)-0.1(0.2)-0.3(0.2)-0.2(0.4)-0.3(0.2)0.1(0.1)

-0.3(0.1)

0(0)

2.94

5e-4

0(0)-0.1(0)

0(0.1)

0(0.2)

0(0)

-0.1(0.1)-0.3(0.1)-0.3(0.4)-0.1(0.1)

0(0.1)-0.3(0)

0(0)

29.38

5e-3

0.1(0)

-0.1(0)

0(0)

0(0.3)0.2(0.1)

0.2(0.2)-0.3(0.2)-0.3(0.1)-0.1(0.1)

0(0.1)-0.3(0.1)0.1(0)

293.77

5e-2

0.2(0)

-0.1(0)

0(0.1)1.6(2.5)1.3(0.3)

0.1(0.4)-0.2(0.1)-0.3(0.1)-0.1(0.2)0.2(0.1)

-0.3(0)

0.4(0.1)

log 1

0(PC10)[mg/ml]

log 1

0(EC50)[mg/ml]


132

C.20 Test item 20

−11 −10 −9 −8 −7 −6 −5 −40

10

20

30

40

50

60

70

80

90

100

log10(M)

Re

lative

In

du

ctio

n [

%]

TI−CIT2TF, run 3, Citoxlab

−11 −10 −9 −8 −7 −6 −5 −40

10

20

30

40

50

60

70

80

90

100

log10(M)

Re

lative

In

du

ctio

n [

%]


−11 −10 −9 −8 −7 −6 −5 −4

10

20

30

40

50

60

70

80

90

100

log10(M)

Re

lative

In

du

ctio

n [

%]


−11 −10 −9 −8 −7 −6 −5 −40

10

20

30

40

50

60

70

80

90

100

log10(M)

Re

lative

In

du

ctio

n [

%]

TI−ENV3EH, run 7, Envigo

−11 −10 −9 −8 −7 −6 −5 −40

10

20

30

40

50

60

70

80

90

log10(M)

Re

lative

In

du

ctio

n [

%]


−11 −10 −9 −8 −7 −6 −5 −40

10

20

30

40

50

60

70

80

90

100

log10(M)

Re

lative

In

du

ctio

n [

%]


−12 −11 −10 −9 −8 −7 −60

10

20

30

40

50

60

70

80

90

100

log10(M)

Re

lative

In

du

ctio

n [

%]

TI−12ZV, run 6, RISE

−12 −11 −10 −9 −8 −7 −60

10

20

30

40

50

60

70

80

90

100

log10(M)

Re

lative

In

du

ctio

n [

%]


−12 −11 −10 −9 −8 −7 −60

10

20

30

40

50

60

70

80

90

100

log10(M)

Re

lative

In

du

ctio

n [

%]


−11 −10 −9 −8 −7 −6 −5 −40

10

20

30

40

50

60

70

80

90

100

log10(M)

Re

lative

In

du

ctio

n [

%]

TI−BDS2MK, run 1, BDS

−11 −10 −9 −8 −7 −6 −5 −40

10

20

30

40

50

60

70

80

90

100

log10(M)

Re

lative

In

du

ctio

n [

%]


−11 −10 −9 −8 −7 −6 −5 −40

10

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100

log10(M)

Re

lative

In

du

ctio

n [

%]



133

−11 −10 −9 −8 −7 −6 −5 −40

10

20

30

40

50

60

70

80

90

100

log10(M)

Rela

tive Induction [%

]

TI−CIT2TF, Citoxlab

run 3

run 12

run 15

DHT

−11 −10 −9 −8 −7 −6 −5 −40

10

20

30

40

50

60

70

80

90

100

log10(M)

Rela

tive Induction [%

]

TI−ENV3EH, Envigo

run 7

run 9

run 10

DHT

−12 −11 −10 −9 −8 −7 −60

10

20

30

40

50

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70

80

90

100

log10(M)

Rela

tive Induction [%

]

TI−12ZV, RISE

run 6

run 12

run 21

DHT

−11 −10 −9 −8 −7 −6 −5 −40

10

20

30

40

50

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70

80

90

100

log10(M)

Rela

tive Induction [%

]

TI−BDS2MK, BDS

run 1

run 3

run 5

DHT


−12 −11 −10 −9 −8 −7 −6 −5 −40

10

20

30

40

50

60

70

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90

100

log10(M)

Rela

tive

In

du

ctio

n [

%]


Citoxlab

Envigo

RISE

BDS

DHT


134

Citoxlab

Envigo

RISE

BDS

run3

run12

run15

run7

run9

run10

run6

run12

run21

run1

run3

run5

[µM]

[mg/ml]

PRE

PRE

PRE

PRE

pre

PRE

PRE

PRE

PRE

PRE

PRE

PRE

5.13e-7

1.5e-10

0.1(0.1)0.1(0.1)0.2(0.4)

5.13e-6

1.5e-9

0.1(0.2)

0(0.1)0.7(0.5)

1.71e-5

5e-9

0(0)

0(0.1)

0(0)

0.1(0.3)

0(0.2)-0.1(0)

0(0.1)-0.2(0)

0(0)

5.13e-5

1.5e-8

0(0.1)

0(0.3)0.1(0.5)

1.71e-4

5e-8

0(0)

-0.1(0)

48.6(1.6)0.2(0.2)

-0.1(0.1)-0.1(0.1)

0(0)

-0.2(0)

0(0)

5.13e-4

1.5e-7

-0.1(0.1)

0(0.1)3.8(0.5)

1.71e-3

5e-7

0(0)

-0.1(0.1)

0.2(0)

0.1(0.1)

0.1(0.1)-0.1(0)

-0.1(0)

-0.2(0)

0(0)

5.13e-3

1.5e-6

-0.1(0.1)-0.2(0.1)0.4(0.3)

1.71e-2

5e-6

0(0)

0(0)

0.1(0)

0.1(0.1)

-0.2(0.1)-0.1(0)

0(0.1)-0.2(0)

0.1(0.1)

5.13e-2

1.5e-5

-0.1(0)

-0.2(0.2)0.1(0.3)

1.71e-1

5e-5

0.1(0)

0(0)

0.1(0)

0.3(0.2)

0.3(0.2)

0(0)

0(0)

-0.2(0)

0.1(0)

5.13e-1

1.5e-4

-0.1(0)

-0.1(0.1)

0(0.2)

1.71

5e-4

0.2(0.1)

0.2(0)

0.2(0)

0.4(0.2)

0.4(0.1)0.1(0)

0.2(0.1)

0(0.1)0.3(0)

5.13

1.5e-3

0.7(0.1)0.6(0.3)0.9(0.1)

17.11

5e-3

2.3(0.3)

2.9(0.2)

2.9(0.2)4.2(0.3)

4.2(0.6)1.9(0.2)

3.6(0.4)1.7(0.1)2.4(0.3)

171.12

5e-2

6(0.2)4.4(0.4)

7(0.5)

9(1.8)

11.7(1.5)7.6(0.5)

8.2(0.7)7.2(0.5)7.7(0.6)

interpvalue(x)

9.5(25)

log 1

0(PC10)[mg/ml]

-8.24

-1.5

log 1

0(EC50)[mg/ml]

nana


135

C.21 Test item 21

−11 −10 −9 −8 −7

10

20

30

40

50

60

70

80

90

100

log10(M)

Re

lative

In

du

ctio

n [

%]

TI−24RY, run 9, RISE

−11 −10 −9 −8 −7

10

20

30

40

50

60

70

80

90

100

log10(M)

Re

lative

In

du

ctio

n [

%]


−11 −10 −9 −8 −7

10

20

30

40

50

60

70

80

90

100

log10(M)

Re

lative

In

du

ctio

n [

%]


Figure 96: Test item 21. Relative induction responses for accepted experiments in three participart-ing labs. Legend: relative Induction Yc ( ), single replicate for Yc ( ), DHT ( ).

−11 −10 −9 −8 −7

10

20

30

40

50

60

70

80

90

100

log10(M)

Rela

tive Induction [%

]

TI−24RY, RISE

run 9

run 17

run 19

DHT


RISErun 9 run 17 run 19

[µM] [mg/ml] COM COM COM4.32e-5 1.35e-8 1.9 (2.1) 0.2 (0) 0.4 (0.1)1.44e-4 4.5e-8 2.4 (0.1) 1.3 (0.6) 2.1 (0)4.32e-4 1.35e-7 11.5(0.8) 7.9 (1.7) 9.5 (1.6)1.44e-3 4.5e-7 28 (0.7) 21.6(4.2) 26.5(3.4)4.32e-3 1.35e-6 39.1(1.4) 38.2(1.5) 42 (0.4)1.44e-2 4.5e-6 46.9(2.5) 48.7(1.7) 48.2(2.6)4.32e-2 1.35e-5 47.6(1.4) 58 (3.6) 49.4(4.4)1.44e-1 4.5e-5 51 (1.4) 57.2(3.7) 51.3(4.6)log10(PC10) [mg/ml] -6.92 -6.77 -6.85log10(EC50) [mg/ml] -6.41 -6.11 -6.38


136

C.22 Test item 22

−11 −10 −9 −8 −7 −6 −50

10

20

30

40

50

60

70

80

90

100

log10(M)

Rela

tive Induction [%

]TI−33TH, run 8, RISE

−12 −11 −10 −9 −8 −7 −60

10

20

30

40

50

60

70

80

90

100

log10(M)

Re

lative

In

du

ctio

n [

%]

TI−33TH, run 10, RISE

−12 −11 −10 −9 −8 −7 −60

10

20

30

40

50

60

70

80

90

100

log10(M)

Re

lative

In

du

ctio

n [

%]


Figure 98: Test item 22. Relative induction responses for accepted experiments in three participart-ing labs. Legend: relative Induction Yc ( ), single replicate for Yc ( ), DHT ( ).

−12 −11 −10 −9 −8 −7 −6 −50

10

20

30

40

50

60

70

80

90

100

log10(M)

Rela

tive Induction [%

]

TI−33TH, RISE

run 8

run 10

run 23

DHT



[µM] [mg/ml] PRE PRE PRE3.6e-7 1.5e-10 -0.1(0.2) 0.5(1.1)3.6e-6 1.5e-9 0.1(0.1) 0.1 (0.2) 0.3(0.9)3.6e-5 1.5e-8 0.1(0.1) -0.1(0.1) 0.3(1.2)3.6e-4 1.5e-7 0 (0.1) -0.1(0.1) 0.2(1.1)3.6e-3 1.5e-6 0.7(0.3) 0.4 (0.1) 0.7(1.2)3.6e-2 1.5e-5 2.2(0.3) 1.8 (0.5) 1.6(0.8)3.6e-1 1.5e-4 3.4(0.2) 2.6 (0.1) 2.2(0.8)3.6 1.5e-3 6.1(0.1) 6.3 (2.2) 4 (0.7)35.98 1.5e-2 cyt/excllog10(PC10) [mg/ml]log10(EC50) [mg/ml]


137

C.23 Test item 23

−11 −10 −9 −8 −7 −6 −50

10

20

30

40

50

60

70

80

90

100

log10(M)

Re

lative

In

du

ctio

n [

%]

TI−27YC, run 5, RISE

−11 −10 −9 −8 −7 −6 −50

10

20

30

40

50

60

70

80

90

100

log10(M)

Re

lative

In

du

ctio

n [

%]


−11 −10 −9 −8 −7 −6 −50

10

20

30

40

50

60

70

80

90

100

log10(M)

Re

lative

In

du

ctio

n [

%]


Figure 100: Test item 23. Relative induction responses for accepted experiments in three partici-parting labs. Legend: relative Induction Yc ( ), single replicate for Yc ( ), DHT ( ).

−11 −10 −9 −8 −7 −6 −50

10

20

30

40

50

60

70

80

90

100

log10(M)

Rela

tive Induction [%

]

TI−27YC, RISE

run 5

run 14

run 23

DHT



[µM] [mg/ml] PRE PRE PRE1.89e-6 5e-10 -0.2(0.2) -0.2(0.1) -0.5(0.1)1.89e-5 5e-9 -0.1(0.1) -0.1(0.2) -0.2(0.6)1.89e-4 5e-8 -0.4(0.1) -0.1(0.2) -0.2(0.6)1.89e-3 5e-7 -0.2(0.1) -0.4(0.1) -0.5(0.1)1.89e-2 5e-6 0.1 (0.1) -0.2(0.1) -0.2(0.1)1.89e-1 5e-5 0.6 (0.2) 0.5 (0.1) 0.1 (0)1.89 5e-4 0.6 (0.2) 0.4 (0.4) 0 (0.1)18.92 5e-3 -0.5(0.1) -0.4(0.2) -0.8(0.1)log10(PC10) [mg/ml]log10(EC50) [mg/ml]


138

C.24 Test item 24

−11 −10 −9 −8 −7 −6 −50

10

20

30

40

50

60

70

80

90

100

log10(M)

Re

lative

In

du

ctio

n [

%]

TI−15SB, run 3, RISE

−11 −10 −9 −8 −7 −6 −50

10

20

30

40

50

60

70

80

90

100

log10(M)

Re

lative

In

du

ctio

n [

%]


−11 −10 −9 −8 −7 −6 −50

10

20

30

40

50

60

70

80

90

100

log10(M)

Re

lative

In

du

ctio

n [

%]



−11 −10 −9 −8 −7 −6 −50

10

20

30

40

50

60

70

80

90

100

log10(M)

Rela

tive Induction [%

]

TI−15SB, RISE

run 3

run 12

run 21

DHT



[µM] [mg/ml] PRE PRE PRE1.53e-6 5e-10 0.1 (0.3) 0 (0.1) -0.2(0.1)1.53e-5 5e-9 -0.1(0.2) 0 (0.1) 0 (0.1)1.53e-4 5e-8 -0.1(0.1) -0.1(0.1) 2 (0.5)1.53e-3 5e-7 0.1 (0.7) -0.1(0.2) -0.2(0.3)1.53e-2 5e-6 -0.2 (0) 0 (0.2) -0.1(0.1)1.53e-1 5e-5 -0.2(0.1) -0.2(0.3) -0.2(0.2)1.53 5e-4 -0.3(0.3) -0.1(0.1) -0.1 (0)15.32 5e-3 -0.6 (0) -0.2(0.1) -0.3(0.2)log10(PC10) [mg/ml]log10(EC50) [mg/ml]


139

C.25 Test item 25

−11 −10 −9 −8 −7

10

20

30

40

50

60

70

80

90

100

log10(M)

Re

lative

In

du

ctio

n [

%]

TI−37VK, run 11, RISE

−11 −10 −9 −8 −70

10

20

30

40

50

60

70

80

90

100

log10(M)

Re

lative

In

du

ctio

n [

%]


−11 −10 −9 −8 −7

10

20

30

40

50

60

70

80

90

100

log10(M)

Re

lative

In

du

ctio

n [

%]



−11 −10 −9 −8 −70

10

20

30

40

50

60

70

80

90

100

log10(M)

Rela

tive Induction [%

]

TI−37VK, RISE

run 11

run 15

run 19

DHT



[µM] [mg/ml] COM COM COM1.64e-5 4.5e-9 0.7 (0.2) 0.2 (0.3) 0.7 (0.1)5.47e-5 1.5e-8 5.3 (0.2) 4.3 (0.2) 4.6 (0.3)1.64e-4 4.5e-8 21 (1.3) 23.8 (4.4) 20.3 (0.5)5.47e-4 1.5e-7 56.8(1.5) 56.2 (4.2) 51.3 (2.8)1.64e-3 4.5e-7 76.4(0.3) 83.2 (4.5) 79.7 (7.1)5.47e-3 1.5e-6 85.4(1.9) 100.1(3.1) 83.2 (6)1.64e-2 4.5e-6 92.4(1.3) 104.8(3.8) 95.9 (6.8)5.47e-2 1.5e-5 98 (3.7) 98 (2) 98.2(10.9)log10(PC10) [mg/ml] -7.61 -7.65 -7.61log10(EC50) [mg/ml] -6.93 -6.89 -6.87


140

C.26 Test item 26

−12 −11 −10 −9 −8 −7 −60

10

20

30

40

50

60

70

80

90

100

log10(M)

Re

lative

In

du

ctio

n [

%]

TI−13GZ, run 2, RISE

−12 −11 −10 −9 −8 −7 −60

10

20

30

40

50

60

70

80

90

100

log10(M)

Re

lative

In

du

ctio

n [

%]


−12 −11 −10 −9 −8 −7 −60

10

20

30

40

50

60

70

80

90

100

log10(M)

Re

lative

In

du

ctio

n [

%]



−12 −11 −10 −9 −8 −7 −60

10

20

30

40

50

60

70

80

90

100

log10(M)

Rela

tive Induction [%

]

TI−13GZ, RISE

run 2

run 12

run 21

DHT



[µM] [mg/ml] PRE PRE PRE4.23e-7 1.5e-10 -0.1(0.1) 0.1 (0.3) -0.3(0.1)4.23e-6 1.5e-9 0 (0.1) -0.1 (0) -0.4(0.1)4.23e-5 1.5e-8 -0.1(0.1) 0 (0.1) -0.1(0.3)4.23e-4 1.5e-7 -0.1(0.1) -0.2(0.2) 1.8 (0.3)4.23e-3 1.5e-6 -0.2 (0) -0.1 (0) 1.3 (0.2)4.23e-2 1.5e-5 -0.2(0.1) -0.2(0.1) -0.4 (0)4.23e-1 1.5e-4 -0.3 (0) -0.1(0.1) -0.4(0.1)4.23 1.5e-3 -0.2(0.1) -0.2(0.2) -0.4(0.1)log10(PC10) [mg/ml]log10(EC50) [mg/ml]


141

C.27 Test item 27

−11 −10 −9 −8 −7 −6 −50

10

20

30

40

50

60

70

80

90

100

log10(M)

Re

lative

In

du

ctio

n [

%]

TI−31RX, run 6, RISE

−11 −10 −9 −8 −7 −6 −50

10

20

30

40

50

60

70

80

90

100

log10(M)

Re

lative

In

du

ctio

n [

%]


−11 −10 −9 −8 −7 −6 −50

10

20

30

40

50

60

70

80

90

100

log10(M)

Re

lative

In

du

ctio

n [

%]



−11 −10 −9 −8 −7 −6 −50

10

20

30

40

50

60

70

80

90

100

log10(M)

Rela

tive Induction [%

]

TI−31RX, RISE

run 6

run 8

run 20

DHT



[µM] [mg/ml] PRE PRE PRE4.68e-6 1.5e-9 0 (0) 0.1 (0) 0 (0.1)4.68e-5 1.5e-8 -0.2(0.1) 0.2 (0.3) 0.2 (0.1)4.68e-4 1.5e-7 0 (0.1) 0.2 (0.1) 0 (0.2)4.68e-3 1.5e-6 -0.2(0.1) 0 (0.2) 0.1 (0.2)4.68e-2 1.5e-5 -0.2(0.1) 0 (0.1) 0.4 (0.1)4.68e-1 1.5e-4 -0.2 (0) 0 (0) -0.1(0.1)4.68 1.5e-3 -0.1(0.1) -0.1 (0) 0.1 (0.2)46.83 1.5e-2 -0.2(0.1) 0.4 (0.2) 0 (0.2)log10(PC10) [mg/ml]log10(EC50) [mg/ml]


142

C.28 Test item 28

−13 −12 −11 −10 −9 −8 −70

10

20

30

40

50

60

70

80

90

100

log10(M)

Re

lative

In

du

ctio

n [

%]

TI−29DC, run 10, RISE

−13 −12 −11 −10 −9 −8 −70

10

20

30

40

50

60

70

80

90

100

log10(M)

Re

lative

In

du

ctio

n [

%]


−13 −12 −11 −10 −9 −8 −70

10

20

30

40

50

60

70

80

90

100

log10(M)

Re

lative

In

du

ctio

n [

%]



−13 −12 −11 −10 −9 −8 −70

10

20

30

40

50

60

70

80

90

100

log10(M)

Rela

tive Induction [%

]

TI−29DC, RISE

run 10

run 16

run 25

DHT



[µM] [mg/ml] PRE PRE PRE5.87e-8 1.5e-11 0 (0.2) -0.3(0.2) 0 (1.4)5.87e-7 1.5e-10 -0.2(0.1) -0.3(0.2) -0.1(1.2)5.87e-6 1.5e-9 0 (0.1) -0.4(0.2) -0.5(0.4)5.87e-5 1.5e-8 -0.1(0.1) -0.3(0.2) -0.7(0.4)5.87e-4 1.5e-7 -0.1(0.1) -0.4(0.2) -0.8(0.2)5.87e-3 1.5e-6 -0.1(0.2) -0.4(0.1) -0.8(0.1)5.87e-2 1.5e-5 -0.2(0.1) -0.5(0.1) -1 (0.2)5.87e-1 1.5e-4 -0.2(0.1) -0.5(0.1) -0.6(0.1)log10(PC10) [mg/ml]log10(EC50) [mg/ml]


143

C.29 Test item 29

−11 −10 −9 −8 −7

10

20

30

40

50

60

70

80

90

100

log10(M)

Re

lative

In

du

ctio

n [

%]

TI−34VE, run 11, RISE

−11 −10 −9 −8 −70

10

20

30

40

50

60

70

80

90

100

log10(M)

Re

lative

In

du

ctio

n [

%]


−11 −10 −9 −8 −7

10

20

30

40

50

60

70

80

90

100

log10(M)

Re

lative

In

du

ctio

n [

%]



−11 −10 −9 −8 −70

10

20

30

40

50

60

70

80

90

100

log10(M)

Rela

tive Induction [%

]

TI−34VE, RISE

run 11

run 15

run 19

DHT



[µM] [mg/ml] COM COM COM1.58e-5 4.5e-9 0.4 (0.3) 0 (0.3) 0.6 (0.1)5.27e-5 1.5e-8 4.4 (0.3) 3.7 (0.3) 3.9 (0.6)1.58e-4 4.5e-8 18.1(1.1) 19.4(1.9) 18.1(0.5)5.27e-4 1.5e-7 46.5(6.7) 50.2(2.8) 45.6(5.3)1.58e-3 4.5e-7 67.2(2.6) 64.8(1.1) 63.6(3.2)5.27e-3 1.5e-6 73.7(4.8) 76.5(4.3) 73.7(3.2)1.58e-2 4.5e-6 78.8(4.3) 80.6(2.6) 77.9(6.1)5.27e-2 1.5e-5 80.2(5.2) 78.6(2.4) 80.1(2.5)log10(PC10) [mg/ml] -7.57 -7.57 -7.56log10(EC50) [mg/ml] -6.94 -6.97 -6.91


144

C.30 Test item 30

−15 −14 −13 −12 −11 −10 −9 −8 −70

10

20

30

40

50

60

70

80

90

100

log10(M)

Re

lative

In

du

ctio

n [

%]

TI−7FK, run 14, RISE

−15 −14 −13 −12 −11 −10 −9 −8 −70

10

20

30

40

50

60

70

80

90

100

log10(M)

Re

lative

In

du

ctio

n [

%]


−15 −14 −13 −12 −11 −10 −9 −8 −70

10

20

30

40

50

60

70

80

90

100

log10(M)

Re

lative

In

du

ctio

n [

%]



−15 −14 −13 −12 −11 −10 −9 −8 −70

10

20

30

40

50

60

70

80

90

100

log10(M)

Rela

tive Induction [%

]

TI−7FK, RISE

run 14

run 23

run 27

DHT



[µM] [mg/ml] PRE PRE PRE3.98e-10 5e-13 0 (0.2) 0.4 (1.3) 0.3 (0.4)3.98e-9 5e-12 -0.1(0.2) 0.3 (1.3) 0 (0.4)3.98e-8 5e-11 -0.2(0.2) 0.4 (1.1) -0.1(0.3)3.98e-7 5e-10 -0.2(0.3) 0.1 (1.3) -0.1(0.1)3.98e-6 5e-9 -0.3(0.1) 0.3 (1.1) -0.1(0.3)3.98e-5 5e-8 -0.1(0.3) 0.1 (0.8) -0.3(0.1)3.98e-4 5e-7 -0.2(0.1) -0.2(0.6) -0.2(0.2)3.98e-3 5e-6 -0.7(0.3) -0.7(0.3) -0.5(0.1)log10(PC10) [mg/ml]log10(EC50) [mg/ml]


145

C.31 Test item 31

−11 −10 −9 −8 −7 −6 −50

10

20

30

40

50

60

70

80

90

100

log10(M)

Rela

tive Induction [%

]TI−1JA, run 1, RISE

−12 −11 −10 −9 −8 −7 −60

10

20

30

40

50

60

70

80

90

100

log10(M)

Re

lative

In

du

ctio

n [

%]

TI−1JA, run 10, RISE

−12 −11 −10 −9 −8 −7 −60

10

20

30

40

50

60

70

80

90

100

log10(M)

Re

lative

In

du

ctio

n [

%]



−12 −11 −10 −9 −8 −7 −6 −50

10

20

30

40

50

60

70

80

90

100

log10(M)

Rela

tive Induction [%

]

TI−1JA, RISE

run 1

run 10

run 18

DHT



[µM] [mg/ml] PRE PRE PRE5.59e-7 1.5e-10 -0.1(0.2) -0.1(0.2)5.59e-6 1.5e-9 1.4 (0.2) -0.2(0.1) 0 (0.4)5.59e-5 1.5e-8 1.6 (0.3) 0 (0.1) -0.1 (0)5.59e-4 1.5e-7 0 (0.1) -0.1(0.2) -0.2(0.3)5.59e-3 1.5e-6 -0.1(0.1) -0.1 (0) -0.1(0.1)5.59e-2 1.5e-5 1 (0.9) -0.1(0.2) -0.4(0.3)5.59e-1 1.5e-4 0.4 (0.1) -0.2(0.1) -0.2(0.1)5.59 1.5e-3 0.2 (0) -0.2(0.2) -0.1 (0)55.89 1.5e-2 cyt/excllog10(PC10) [mg/ml]log10(EC50) [mg/ml]


146

C.32 Test item 32

−11 −10 −9 −8 −7 −6 −50

10

20

30

40

50

60

70

80

90

100

log10(M)

Re

lative

In

du

ctio

n [

%]

TI−19TM, run 3, RISE

−11 −10 −9 −8 −7 −6 −50

10

20

30

40

50

60

70

80

90

100

log10(M)

Rela

tive Induction [%

]


−12 −11 −10 −9 −8 −7 −60

10

20

30

40

50

60

70

80

90

100

log10(M)

Re

lative

In

du

ctio

n [

%]



−12 −11 −10 −9 −8 −7 −6 −50

10

20

30

40

50

60

70

80

90

100

log10(M)

Rela

tive Induction [%

]

TI−19TM, RISE

run 3

run 14

run 18

DHT



[µM] [mg/ml] PRE PRE PRE6.44e-7 5e-10 -0.1(0.2)6.44e-6 5e-9 0 (0.2) 0.4 (0.4) -0.2(0.1)6.44e-5 5e-8 0 (0.2) -0.1(0.2) -0.3(0.5)6.44e-4 5e-7 0 (0.1) -0.1(0.2) 0 (0.1)6.44e-3 5e-6 -0.1(0.2) -0.4(0.1) -0.1(0.1)6.44e-2 5e-5 -0.1(0.1) -0.4(0.1) -0.3(0.1)6.44e-1 5e-4 -0.2(0.2) -0.3(0.1) -0.1(0.2)6.44 5e-3 -0.2(0.1) -0.3(0.2) -0.2(0.2)64.36 5e-2 -0.7(0.2) cyt/excllog10(PC10) [mg/ml]log10(EC50) [mg/ml]


147

C.33 Test item 33

−11 −10 −9 −8 −7 −6 −50

10

20

30

40

50

60

70

80

90

100

log10(M)

Re

lative

In

du

ctio

n [

%]

TI−5BR, run 1, RISE

−11 −10 −9 −8 −7 −6 −50

10

20

30

40

50

60

70

80

90

100

log10(M)

Re

lative

In

du

ctio

n [

%]


−11 −10 −9 −8 −7 −6 −50

10

20

30

40

50

60

70

80

90

100

log10(M)

Re

lative

In

du

ctio

n [

%]



−11 −10 −9 −8 −7 −6 −50

10

20

30

40

50

60

70

80

90

100

log10(M)

Rela

tive Induction [%

]

TI−5BR, RISE

run 1

run 16

run 23

DHT



[µM] [mg/ml] PRE PRE PRE1.33e-6 5e-10 -0.1 (0) -0.7(0.2) -0.5(0.1)1.33e-5 5e-9 1.4 (0.2) -0.8(0.2) -0.6(0.1)1.33e-4 5e-8 0.3 (0.3) 0.9 (0.4) -0.4(0.1)1.33e-3 5e-7 2 (0.1) -1.1(0.1) -0.5(0.1)1.33e-2 5e-6 0.3 (0.1) -1.1(0.1) -0.5(0.1)1.33e-1 5e-5 0 (0.2) -0.9(0.1) -0.6(0.1)1.33 5e-4 -0.1(0.2) -0.8 (0) -0.5 (0)13.3 5e-3 0 (0) -0.8(0.2) -0.5(0.1)log10(PC10) [mg/ml]log10(EC50) [mg/ml]


148

C.34 Test item 34

−11 −10 −9 −8 −70

10

20

30

40

50

60

70

80

90

100

log10(M)

Re

lative

In

du

ctio

n [

%]

TI−36XY, run 11, RISE

−11 −10 −9 −8 −70

10

20

30

40

50

60

70

80

90

100

log10(M)

Re

lative

In

du

ctio

n [

%]


−11 −10 −9 −8 −70

10

20

30

40

50

60

70

80

90

100

log10(M)

Re

lative

In

du

ctio

n [

%]



−11 −10 −9 −8 −70

10

20

30

40

50

60

70

80

90

100

log10(M)

Rela

tive Induction [%

]

TI−36XY, RISE

run 11

run 15

run 19

DHT



[µM] [mg/ml] COM COM COM4.41e-5 1.5e-8 0.1 (0.1)1.32e-4 4.5e-8 -0.7 (0) 0 (0.1)1.47e-4 5e-8 0.1 (0.1)4.41e-4 1.5e-7 0.4 (0) -0.5 (0.2) 0.6 (0.4)1.32e-3 4.5e-7 2 (0.2) 2.3 (0.5)1.47e-3 5e-7 3.6 (0.2)4.41e-3 1.5e-6 12 (0.9) 11.2(1.3) 9.6 (0.4)1.32e-2 4.5e-6 23.9(3.5) 21.2(0.3)1.47e-2 5e-6 23.1(0.8)4.41e-2 1.5e-5 30.1(1.4) 30.8(3.5) 30.7(3.8)1.32e-1 4.5e-5 35.6(1.8) 32.3(0.7)1.47e-1 5e-5 33.1 (1)4.41e-1 1.5e-4 35.7(2.8) 33.8 (1)log10(PC10) [mg/ml] -5.92 -5.87 -5.81log10(EC50) [mg/ml] -5.59 -5.56 -5.53


149

C.35 Test item 35

−11 −10 −9 −8 −7 −6 −50

10

20

30

40

50

60

70

80

90

100

log10(M)

Re

lative

In

du

ctio

n [

%]

TI−23QM, run 6, RISE

−12 −11 −10 −9 −8 −7 −60

10

20

30

40

50

60

70

80

90

100

log10(M)

Re

lative

In

du

ctio

n [

%]


−12 −11 −10 −9 −8 −7 −60

10

20

30

40

50

60

70

80

90

100

log10(M)

Re

lative

In

du

ctio

n [

%]



−12 −11 −10 −9 −8 −7 −6 −50

10

20

30

40

50

60

70

80

90

100

log10(M)

Rela

tive Induction [%

]

TI−23QM, RISE

run 6

run 8

run 18

DHT



[µM] [mg/ml] PRE PRE PRE1.08e-7 5e-11 0 (0) 0 (0.2)1.08e-6 5e-10 -0.1(0.1) -0.1(0.1) 0.1 (0.2)1.08e-5 5e-9 -0.1(0.1) 0 (0) -0.1(0.3)1.08e-4 5e-8 0 (0.1) -0.1(0.1) -0.1(0.1)1.08e-3 5e-7 -0.1(0.1) -0.1 (0) -0.3(0.2)1.08e-2 5e-6 -0.1 (0) 0 (0.3) -0.1(0.2)1.08e-1 5e-5 -0.1(0.1) -0.3(0.1) -0.2(0.2)1.08 5e-4 -0.1(0.1) -0.2(0.2) -0.4(0.2)10.83 5e-3 cyt/excllog10(PC10) [mg/ml]log10(EC50) [mg/ml]


150

C.36 Test item 36

−11 −10 −9 −8 −7 −6 −50

10

20

30

40

50

60

70

80

90

100

log10(M)

Rela

tive Induction [%

]TI−10JQ, run 1, RISE

−12 −11 −10 −9 −8 −7 −60

10

20

30

40

50

60

70

80

90

100

log10(M)

Re

lative

In

du

ctio

n [

%]

TI−10JQ, run 12, RISE

−12 −11 −10 −9 −8 −7 −60

10

20

30

40

50

60

70

80

90

100

log10(M)

Re

lative

In

du

ctio

n [

%]



−12 −11 −10 −9 −8 −7 −6 −50

10

20

30

40

50

60

70

80

90

100

log10(M)

Rela

tive Induction [%

]

TI−10JQ, RISE

run 1

run 12

run 21

DHT



[µM] [mg/ml] PRE PRE PRE4.77e-7 1.5e-10 0 (0.2) -0.1(0.1)4.77e-6 1.5e-9 0 (0.1) 0 (0.2) -0.2(0.1)4.77e-5 1.5e-8 0 (0.1) 0.1(0.1) -0.1(0.2)4.77e-4 1.5e-7 0 (0.1) 0 (0) -0.2(0.1)4.77e-3 1.5e-6 0.2 (0) 0.2(0.3) 0.1 (0.2)4.77e-2 1.5e-5 1.1(0.2) 1 (0.4) 0.8 (0.3)4.77e-1 1.5e-4 2.2(0.3) 1.5(0.5) 1.8 (0.1)4.77 1.5e-3 8.9(0.7) 9.8(1.2) 8.3 (0.3)47.69 1.5e-2 cyt/excllog10(PC10) [mg/ml]log10(EC50) [mg/ml]


151

C.37 Test item 37

−11 −10 −9 −8 −7 −6 −50

10

20

30

40

50

60

70

80

90

100

log10(M)

Re

lative

In

du

ctio

n [

%]

TI−4NQ, run 1, RISE

−11 −10 −9 −8 −7 −6 −50

10

20

30

40

50

60

70

80

90

100

log10(M)

Re

lative

In

du

ctio

n [

%]


−11 −10 −9 −8 −7 −6 −50

10

20

30

40

50

60

70

80

90

100

log10(M)

Re

lative

In

du

ctio

n [

%]



−11 −10 −9 −8 −7 −6 −50

10

20

30

40

50

60

70

80

90

100

log10(M)

Rela

tive Induction [%

]

TI−4NQ, RISE

run 1

run 10

run 21

DHT



[µM] [mg/ml] PRE PRE PRE6.02e-6 1.5e-9 -0.1(0.1) -0.1(0.2) 0 (0.2)6.02e-5 1.5e-8 0.8 (0.1) 0.1 (0.1) 0.2 (0.3)6.02e-4 1.5e-7 -0.1 (0) -0.1(0.1) 0 (0)6.02e-3 1.5e-6 0.5 (0.1) 0 (0.1) 0 (0.1)6.02e-2 1.5e-5 -0.1 (0) -0.1(0.2) -0.1(0.1)6.02e-1 1.5e-4 0.1 (0) -0.2 (0) 0 (0.2)6.02 1.5e-3 0.3 (0) 0.2 (0.2) 0.2 (0.2)60.22 1.5e-2 0.3 (0.1) 0.1 (0.1) 0.4 (0.1)log10(PC10) [mg/ml]log10(EC50) [mg/ml]


152

C.38 Test item 38

−11 −10 −9 −8 −7

10

20

30

40

50

60

70

80

90

100

log10(M)

Re

lative

In

du

ctio

n [

%]

TI−25RV, run 9, RISE

−11 −10 −9 −8 −7

10

20

30

40

50

60

70

80

90

100

log10(M)

Re

lative

In

du

ctio

n [

%]


−11 −10 −9 −8 −7

10

20

30

40

50

60

70

80

90

100

log10(M)

Re

lative

In

du

ctio

n [

%]



−11 −10 −9 −8 −7

10

20

30

40

50

60

70

80

90

100

log10(M)

Rela

tive Induction [%

]

TI−25RV, RISE

run 9

run 24

run 26

DHT



[µM] [mg/ml] COM COM COM4.46e-5 1.35e-8 1.2 (0.1) 1 (0.5) 1.1 (1.7)1.49e-4 4.5e-8 7.5 (0.2) 6.1 (0.5) 4.6 (1.9)4.46e-4 1.35e-7 24.2(1.2) 24 (1.8) 18.3(1.8)1.49e-3 4.5e-7 49.4(2.2) 51.4 (1) 47.6(2.5)4.46e-3 1.35e-6 65.2(2.7) 71.9(2.2) 64.2(4.6)1.49e-2 4.5e-6 68.8(0.2) 77.7(3.1) 78.4 (1)4.46e-2 1.35e-5 70.2(1.5) 81.5(1.9) 77.8(0.9)1.49e-1 4.5e-5 72.3(2.3) 79.9(1.3) 77.6(2.7)log10(PC10) [mg/ml] -7.25 -7.22 -7.09log10(EC50) [mg/ml] -6.63 -6.55 -6.47


153

C.39 Test item 39

−11 −10 −9 −8 −7 −6 −50

10

20

30

40

50

60

70

80

90

100

log10(M)

Re

lative

In

du

ctio

n [

%]

TI−16UA, run 2, RISE

−11 −10 −9 −8 −7 −6 −50

10

20

30

40

50

60

70

80

90

100

log10(M)

Re

lative

In

du

ctio

n [

%]


−11 −10 −9 −8 −7 −6 −50

10

20

30

40

50

60

70

80

90

100

log10(M)

Re

lative

In

du

ctio

n [

%]



−11 −10 −9 −8 −7 −6 −50

10

20

30

40

50

60

70

80

90

100

log10(M)

Rela

tive Induction [%

]

TI−16UA, RISE

run 2

run 14

run 18

DHT



[µM] [mg/ml] PRE PRE PRE9.99e-6 1.5e-9 0 (0.2) -0.2(0.1) 0 (0.3)9.99e-5 1.5e-8 -0.1(0.2) -0.3(0.3) -0.1(0.1)9.99e-4 1.5e-7 -0.1(0.1) -0.2(0.3) 0 (0.1)9.99e-3 1.5e-6 -0.1 (0) -0.3(0.2) -0.2(0.2)9.99e-2 1.5e-5 -0.1(0.2) -0.4(0.2) -0.2(0.1)9.99e-1 1.5e-4 -0.2(0.1) -0.2(0.2) -0.2 (0)9.99 1.5e-3 -0.3(0.1) -0.4(0.1) -0.2(0.1)99.87 1.5e-2 -0.2(0.1) -0.5 (0) -0.3(0.1)log10(PC10) [mg/ml]log10(EC50) [mg/ml]


154

C.40 Test item 40

−11 −10 −9 −8 −7 −6 −5 −40

10

20

30

40

50

60

70

80

90

100

log10(M)

Re

lative

In

du

ctio

n [

%]

TI−8WJ, run 1, RISE

−11 −10 −9 −8 −7 −6 −5 −40

10

20

30

40

50

60

70

80

90

100

log10(M)

Re

lative

In

du

ctio

n [

%]


−11 −10 −9 −8 −7 −6 −5 −40

10

20

30

40

50

60

70

80

90

100

log10(M)

Re

lative

In

du

ctio

n [

%]



−11 −10 −9 −8 −7 −6 −5 −40

10

20

30

40

50

60

70

80

90

100

log10(M)

Rela

tive Induction [%

]

TI−8WJ, RISE

run 1

run 10

run 18

DHT



[µM] [mg/ml] PRE PRE PRE1.44e-5 5e-9 -0.1(0.1) -0.1(0.1) 0 (0.1)1.44e-4 5e-8 -0.1(0.1) -0.1(0.1) -0.2(0.1)1.44e-3 5e-7 0 (0.1) -0.2(0.1) -0.2(0.2)1.44e-2 5e-6 0 (0.1) -0.3(0.1) -0.1(0.2)1.44e-1 5e-5 0 (0.1) 0 (0.2) 0 (0.1)1.44 5e-4 0.2 (0.1) 0 (0.1) 0 (0.2)14.43 5e-3 0.7 (0.2) 0.6 (0.1) 0.5 (0.2)144.3 5e-2 4.6 (0.5) 5.3 (0.4) 5.4 (1)log10(PC10) [mg/ml]log10(EC50) [mg/ml]


155

C.41 Test item 41

−11 −10 −9 −8 −7 −6 −50

10

20

30

40

50

60

70

80

90

100

log10(M)

Re

lative

In

du

ctio

n [

%]

TI−6MG, run 1, RISE

−11 −10 −9 −8 −7 −6 −50

10

20

30

40

50

60

70

80

90

100

log10(M)

Re

lative

In

du

ctio

n [

%]


−11 −10 −9 −8 −7 −6 −50

10

20

30

40

50

60

70

80

90

100

log10(M)

Re

lative

In

du

ctio

n [

%]



−11 −10 −9 −8 −7 −6 −50

10

20

30

40

50

60

70

80

90

100

log10(M)

Rela

tive Induction [%

]

TI−6MG, RISE

run 1

run 10

run 18

DHT



[µM] [mg/ml] PRE PRE PRE2.82e-6 1.5e-9 0 (0.2) 0 (0.2) 0 (0.2)2.82e-5 1.5e-8 0 (0) -0.1(0.2) 0.3 (0.1)2.82e-4 1.5e-7 -0.1 (0) -0.1(0.1) -0.1(0.1)2.82e-3 1.5e-6 0.3 (0.2) -0.1(0.2) 0 (0.1)2.82e-2 1.5e-5 -0.1(0.1) -0.2 (0) -0.1(0.4)2.82e-1 1.5e-4 0 (0.2) -0.3(0.1) -0.3(0.2)2.82 1.5e-3 -0.2(0.2) -0.3 (0) -0.4(0.1)28.23 1.5e-2 -0.3(0.1) -0.6 (0) -0.3(0.3)log10(PC10) [mg/ml]log10(EC50) [mg/ml]


156

C.42 Test item 42

−11 −10 −9 −8 −7 −6 −5 −40

10

20

30

40

50

60

70

80

90

100

log10(M)

Rela

tive Induction [%

]TI−14FX, run 2, RISE

−11 −10 −9 −8 −7 −6 −50

10

20

30

40

50

60

70

80

90

100

log10(M)

Re

lative

In

du

ctio

n [

%]

TI−14FX, run 12, RISE

−11 −10 −9 −8 −7 −6 −50

10

20

30

40

50

60

70

80

90

100

log10(M)

Re

lative

In

du

ctio

n [

%]



−11 −10 −9 −8 −7 −6 −5 −40

10

20

30

40

50

60

70

80

90

100

log10(M)

Rela

tive Induction [%

]

TI−14FX, RISE

run 2

run 12

run 21

DHT



[µM] [mg/ml] PRE PRE PRE1.34e-6 5e-10 0 (0.2) 0.1 (0.7)1.34e-5 5e-9 -0.1 (0) 0.1 (0.3) 0 (0.7)1.34e-4 5e-8 0 (0.1) -0.1(0.1) -0.1(0.5)1.34e-3 5e-7 -0.2(0.1) -0.1(0.3) -0.1(0.6)1.34e-2 5e-6 -0.1(0.1) -0.2(0.1) -0.2(0.3)1.34e-1 5e-5 -0.1(0.1) -0.2(0.1) -0.1(0.7)1.34 5e-4 -0.3(0.1) -0.1(0.1) -0.2(0.3)13.42 5e-3 -0.3(0.1) -0.4(0.1) -0.4(0.1)134.23 5e-2 cyt/excllog10(PC10) [mg/ml]log10(EC50) [mg/ml]


157

C.43 Test item 43

−12 −11 −10 −9 −8 −7 −60

10

20

30

40

50

60

70

80

90

100

log10(M)

Re

lative

In

du

ctio

n [

%]

TI−26XR, run 1, RISE

−12 −11 −10 −9 −8 −7 −60

10

20

30

40

50

60

70

80

90

100

log10(M)

Re

lative

In

du

ctio

n [

%]


−12 −11 −10 −9 −8 −7 −60

10

20

30

40

50

60

70

80

90

100

log10(M)

Re

lative

In

du

ctio

n [

%]



−12 −11 −10 −9 −8 −7 −60

10

20

30

40

50

60

70

80

90

100

log10(M)

Rela

tive Induction [%

]

TI−26XR, RISE

run 1

run 2

run 3

DHT



[µM] [mg/ml] PRE PRE PRE2.47e-7 1.5e-10 -0.1(0.1) 0 (0.1) -0.1(0.1)2.47e-6 1.5e-9 -0.1(0.1) 0 (0.1) -0.2(0.2)2.47e-5 1.5e-8 -0.1(0.1) 0 (0.1) -0.1(0.1)2.47e-4 1.5e-7 -0.2(0.1) 0 (0.2) -0.3(0.2)2.47e-3 1.5e-6 0 (0.2) -0.1(0.2) -0.1(0.1)2.47e-2 1.5e-5 0.3 (0.3) -0.2(0.1) -0.2(0.1)2.47e-1 1.5e-4 0 (0.1) -0.2(0.1) -0.3(0.1)2.47 1.5e-3 -0.3(0.1) -0.2(0.1) -0.5(0.2)log10(PC10) [mg/ml]log10(EC50) [mg/ml]


158

C.44 Test item 44

−11 −10 −9 −8 −7 −6 −5 −40

10

20

30

40

50

60

70

80

90

100

log10(M)

Rela

tive Induction [%

]TI−21DS, run 3, RISE

−11 −10 −9 −8 −7 −6 −50

10

20

30

40

50

60

70

80

90

100

log10(M)

Re

lative

In

du

ctio

n [

%]

TI−21DS, run 14, RISE

−11 −10 −9 −8 −7 −6 −50

10

20

30

40

50

60

70

80

90

100

log10(M)

Rela

tive Induction [%

]



−11 −10 −9 −8 −7 −6 −5 −40

10

20

30

40

50

60

70

80

90

100

log10(M)

Rela

tive Induction [%

]

TI−21DS, RISE

run 3

run 14

run 21

DHT



[µM] [mg/ml] PRE PRE PRE1.78e-6 5e-10 -0.1(0.4) 0.1 (0.5)1.78e-5 5e-9 -0.2(0.1) -0.1(0.1) 0.2 (0.3)1.78e-4 5e-8 -0.2(0.1) 0 (0.3) 0 (0.4)1.78e-3 5e-7 -0.1(0.2) -0.3(0.3) 0 (0.5)1.78e-2 5e-6 -0.2(0.1) -0.2(0.3) 0.2 (0.5)1.78e-1 5e-5 0.6 (0.1) 0.4 (0.3) 0.6 (0.4)1.78 5e-4 -0.4(0.1) 0.3 (0.1) -0.2(0.2)17.77 5e-3 -0.8(0.1) -0.5(0.1) cyt/excl177.68 5e-2 cyt/excllog10(PC10) [mg/ml]log10(EC50) [mg/ml]


159

C.45 Test item 45

−11 −10 −9 −8 −7 −60

10

20

30

40

50

60

70

80

90

100

log10(M)

Re

lative

In

du

ctio

n [

%]

TI−35VR, run 15, RISE

−11 −10 −9 −8 −7 −6 −5

10

20

30

40

50

60

70

80

90

100

log10(M)

Re

lative

In

du

ctio

n [

%]


−11 −10 −9 −8 −7 −6 −5

10

20

30

40

50

60

70

80

90

100

log10(M)

Re

lative

In

du

ctio

n [

%]



−11 −10 −9 −8 −7 −6 −50

10

20

30

40

50

60

70

80

90

100

log10(M)

Rela

tive Induction [%

]

TI−35VR, RISE

run 15

run 19

run 22

DHT



[µM] [mg/ml] COM COM COM1.51e-4 4.5e-8 -0.6 (0.1) 0.2 (0.1) 0.3 (0.5)5.03e-4 1.5e-7 0.7 (0.2) 1.2 (0.2) 1.5 (0.8)1.51e-3 4.5e-7 5.1 (0.3) 5.1 (0.3) 5.5 (0.5)5.03e-3 1.5e-6 19.5(0.9) 18.4 (1) 17.4(0.7)1.51e-2 4.5e-6 28.5(1.5) 29.2(2.8) 28 (1.7)1.68e-2 5e-6 28 (1) 30.9(0.8)5.03e-2 1.5e-5 35.6(1.7) 34.1(2.8) 34.2(1.8)1.51e-1 4.5e-5 37.3(2.7) 37.4(3.2) 33.8(1.1)1.68e-1 5e-5 33.9(1.4) 33 (0.7)5.03e-1 1.5e-4 39 (2.8) 40 (2.1) 37.8 (1)1.51 4.5e-4 44.3(1.4)1.68 5e-4 41.6(1.8) 43.3(0.9)5.03 1.5e-3 50.9(3.1) 49.4(2.8) 44.7(1.4)16.76 5e-3 45.5(1.9) 43.3(1.3)log10(PC10) [mg/ml] -6.15 -6.09 -6.16log10(EC50) [mg/ml] -5.63 -5.57 -5.67


160

C.46 Test item 46

−11 −10 −9 −8 −7 −6 −50

10

20

30

40

50

60

70

80

90

100

log10(M)

Re

lative

In

du

ctio

n [

%]

TI−2LU, run 1, RISE

−11 −10 −9 −8 −7 −6 −50

10

20

30

40

50

60

70

80

90

100

log10(M)

Re

lative

In

du

ctio

n [

%]


−11 −10 −9 −8 −7 −6 −50

10

20

30

40

50

60

70

80

90

100

log10(M)

Re

lative

In

du

ctio

n [

%]



−11 −10 −9 −8 −7 −6 −50

10

20

30

40

50

60

70

80

90

100

log10(M)

Rela

tive Induction [%

]

TI−2LU, RISE

run 1

run 10

run 18

DHT



[µM] [mg/ml] PRE PRE PRE1.16e-6 5e-10 13.1(1.2) 0 (0.1) -0.2(0.1)1.16e-5 5e-9 0 (0.1) -0.1(0.1) -0.3(0.2)1.16e-4 5e-8 0.1 (0) -0.1(0.1) -0.2(0.2)1.16e-3 5e-7 0 (0.1) 0.2 (0.1) -0.1(0.1)1.16e-2 5e-6 1.6 (0.1) 1.9 (0.2) 0.7 (0.5)1.16e-1 5e-5 5.4 (0.3) 6.1 (0.7) 4.4 (0.8)1.16 5e-4 6.7 (0) 7 (0.6) 5.7 (0.1)11.64 5e-3 3.7 (0.6) 2.9 (0.5) 2.8 (0.3)log10(PC10) [mg/ml]log10(EC50) [mg/ml] na


161

C.47 Test item 3 (2)

−11 −10 −9 −8 −7 −6 −50

10

20

30

40

50

60

70

80

90

100

log10(M)

Re

lative

In

du

ctio

n [

%]

TI−17AR, run 1, RISE

−11 −10 −9 −8 −7 −6 −50

10

20

30

40

50

60

70

80

90

100

log10(M)

Re

lative

In

du

ctio

n [

%]


−11 −10 −9 −8 −7 −6 −50

10

20

30

40

50

60

70

80

90

100

log10(M)

Re

lative

In

du

ctio

n [

%]



−11 −10 −9 −8 −7 −6 −50

10

20

30

40

50

60

70

80

90

100

log10(M)

Rela

tive Induction [%

]

TI−17AR, RISE

run 1

run 2

run 3

DHT



[µM] [mg/ml] PRE PRE PRE3.6e-6 1.5e-9 -0.1(0.2) 0 (0.1) 0 (0.2)3.6e-5 1.5e-8 0 (0) -0.1(0.1) 0.1 (0.1)3.6e-4 1.5e-7 -0.2(0.1) -0.1(0.1) -0.3(0.1)3.6e-3 1.5e-6 -0.1 (0) 0 (0.1) -0.1(0.1)3.6e-2 1.5e-5 2 (0.1) 1.9 (0.5) 2.4 (0.5)3.6e-1 1.5e-4 4.8 (0.4) 6 (0.2) 5.5 (0.4)3.6 1.5e-3 7.1 (0.6) 6.9 (0.7) 6.5 (0.6)36.01 1.5e-2 5.8 (0.2) 8 (0.2) 6.1 (0.7)log10(PC10) [mg/ml]log10(EC50) [mg/ml]


162

Appendix D Responses - antagonist

163

D.1 Test item 1

−11 −10 −9 −8 −7 −6 −5

020406080

100120140160180200220240260280300320340360380400420440460480500520

log10(M)

Re

lative

In

du

ctio

n [

%]


−11 −10 −9 −8 −7 −6 −5

20

40

60

80

100

120

140

160

180

200

220

240

260

280

300

320

log10(M)

Re

lative

In

du

ctio

n [

%]


−11 −10 −9 −8 −7 −6 −5

20

40

60

80

100

120

140

160

180

200

220

240

260

280

log10(M)

Re

lative

In

du

ctio

n [

%]


−8 −7 −6 −5 −40

20

40

60

80

100

120

140

160

180

200

220

240

260

log10(M)

Re

lative

In

du

ctio

n [

%]


−8 −7 −6 −5 −40

20

40

60

80

100

120

140

160

180

200

220

240

log10(M)

Re

lative

In

du

ctio

n [

%]


−8 −7 −6 −5 −40

20

40

60

80

100

120

140

160

180

log10(M)

Re

lative

In

du

ctio

n [

%]


−11 −10 −9 −8 −7 −6 −50

20

40

60

80

100

120

140

160

180

200

220

log10(M)

Rela

tive Induction [%

]


−12 −11 −10 −9 −8 −7 −6 −50

20

40

60

80

100

120

140

160

log10(M)

Rela

tive Induction [%

]


−12 −11 −10 −9 −8 −7 −6 −50

20

40

60

80

100

120

140

160

180

200

log10(M)

Rela

tive Induction [%

]


−10 −9 −8 −7 −6 −5 −4

20

40

60

80

100

120

140

160

180

200

220

240

260

280

log10(M)

Re

lative

In

du

ctio

n [

%]


−10 −9 −8 −7 −6 −5 −40

20

40

60

80

100

120

140

160

180

200

log10(M)

Rela

tive Induction [%

]


−10 −9 −8 −7 −6 −5 −40

20

40

60

80

100

120

140

160

180

200

220

240

260

log10(M)

Rela

tive Induction [%

]


Figure 150: Test item 1. Relative induction responses for accepted experiments in three participart-ing labs. Legend: relative Induction Yc ( ), Specificity control Sc ( ), single replicate for Yc ( ),single replicate for Y S

c (x), Flutamide ( ).

164

−11 −10 −9 −8 −7 −6 −5

020406080

100120140160180200220240260280300320340360380400420440460480500520

log10(M)

Re

lative

In

du

ctio

n*

[%]


−11 −10 −9 −8 −7 −6 −5

20

40

60

80

100

120

140

160

180

200

220

240

260

280

300

320

log10(M)R

ela

tive

In

du

ctio

n*

[%]


−11 −10 −9 −8 −7 −6 −5

20

40

60

80

100

120

140

160

180

200

220

240

260

280

log10(M)

Re

lative

In

du

ctio

n*

[%]


−8 −7 −6 −5 −40

20

40

60

80

100

120

140

160

180

200

220

240

260

log10(M)

Rela

tive I

nduction*

[%]

TI−ENV2VP, run 5, Envigo, int=97.62

−8 −7 −6 −5 −40

20

40

60

80

100

120

140

160

180

200

log10(M)

Rela

tive I

nduction*

[%]


−8 −7 −6 −5 −40

20

40

60

80

100

120

140

160

180

log10(M)

Re

lative

In

du

ctio

n*

[%]


−11 −10 −9 −8 −7 −6 −50

20

40

60

80

100

120

140

160

180

200

220

log10(M)

Rela

tive Induction*

[%]


−12 −11 −10 −9 −8 −7 −6 −50

20

40

60

80

100

120

140

160

log10(M)

Rela

tive Induction*

[%]


−12 −11 −10 −9 −8 −7 −6 −50

20

40

60

80

100

120

140

160

180

200

log10(M)

Rela

tive Induction*

[%]


−10 −9 −8 −7 −6 −5 −4

20

40

60

80

100

120

140

160

180

200

220

240

260

280

log10(M)

Re

lative

In

du

ctio

n*

[%]

TI−BDS2SQ, run 1, BDS, int=78.71

−10 −9 −8 −7 −6 −5 −40

20

40

60

80

100

120

140

160

180

200

log10(M)

Rela

tive Induction*

[%]


−10 −9 −8 −7 −6 −5 −40

20

40

60

80

100

120

140

160

180

200

220

240

260

log10(M)

Rela

tive Induction*

[%]


Figure 151: Test item 1. Normalized Relative induction responses for accepted experiments in threeparticiparting labs. Legend: relative Induction Yc ( ), normalized Specificity control Sn

c (= Sc/Sc1)( ), single replicate for Yc ( ), single replicate for Y S

c (x), Flutamide ( ), interpolated value ( ).

165

−11 −10 −9 −8 −7 −6 −5

020406080

100120140160180200220240260280300320340360380400420440460480

log10(M)

Rela

tive Induction [%

]

TI−CIT2CB, Citoxlab

run 1

run 5

run 13

Flutamide

−8 −7 −6 −5 −40

20

40

60

80

100

120

140

160

180

200

220

240

log10(M)

Rela

tive Induction [%

]

TI−ENV2VP, Envigo

run 5

run 6

run 7

Flutamide

−12 −11 −10 −9 −8 −7 −6 −50

20

40

60

80

100

120

140

160

180

200

log10(M)

Rela

tive Induction [%

]

TI−08WT, RISE

run 1

run 4

run 9

Flutamide

−10 −9 −8 −7 −6 −5 −40

20

40

60

80

100

120

140

160

180

200

220

240

260

log10(M)

Rela

tive Induction [%

]

TI−BDS2SQ, BDS

run 1

run 3

run 4

Flutamide

Figure 152: Test item 1. Relative induction responses for accepted experiments in three participart-ing labs. Aggregated by laboratory.

166

Citoxlab

Envigo

RISE

BDS

run1

run5

run13

run5

run6

run7

run1

run4

run9

run1

run3

run4

[µM]

[mg/ml]

PRE

PRE

PRE

COM

COM

COM

PRE

PRE

PRE

PRE

PRE

PRE

5.55e-7

1.5e-10

101.8(1.2)

116.6(3.7)

1.85e-6

5e-10

463.8(12.6)

96(5.9)

112(4.4)

5.55e-6

1.5e-9

103(7.8)

96(8.7)158.8(9.9)

1.85e-5

5e-9

124.9(2.9)103.1(6.9)126.6(7)

109.9(13.5)

103.9(11)

111.4(2.4)

5.55e-5

1.5e-8

120.9(5.4)

97.7(4.5)143.8(8.6)

1.85e-4

5e-8

276.8(4.6)155.2(5.3)173.3(8.1)

149.7(15.1)

136.2(6.1)158.2(6)

5.55e-4

1.5e-7

170.3(4.3)

94.1(5.4)162.5(10.7)

1.85e-3

5e-7

456.5(18.5)280.7(20.8)

243(18.2)

214.2(13.9)

185.7(17.1)231.2(6.2)

5.55e-3

1.5e-6

197.8(26.8)99.7(5)

178.4(10.7)

1.85e-2

5e-6

485.1(35.5)315.6(2.5)279.2(11.5)

241.7(29.1)

186.9(15.7)

266(5.9)

5.55e-2

1.5e-5

234.8(24.9)

189.1(10.7)

155.3(18.4)

211.2(11.6)100.6(4.1)

176.4(7.3)

1.85e-1

5e-5

496.7(10.6)313.7(3)

268.8(6.5)

240.6(11.2)

172.8(6.7)

163.5(29.9)

245.6(34.4)

192(24.6)

257(7.5)

5.55e-1

1.5e-4

244.8(23.1)

183.1(16.2)

168.4(20.7)

206(2.4)129.6(3.7)

182.4(8.5)

1.85

5e-4

499.8(19.4)308.9(25.1)260.2(14.4)245.4(32.3)

195.6(9.5)

158.7(11)

239.8(20.2)

156.7(13)

253.7(16.5)

5.55

1.5e-3

228.8(26.7)

173.2(21.6)

151.7(22.6)

203.8(9.1)167.4(8.7)

193.6(9.8)

18.49

5e-3

380.9(20.1)268.6(18.7)

216(5.6)

172.4(150.5)156.1(8.7)

143.9(22.2)

194.8(16.8)

183(15.7)

225.3(4.5)

55.47

1.5e-2

156.3(21.7)

82.9

(3.5)

100.4(8.5)

cyt/excl

184.91

5e-2

17.9(4.2)

12.7

(1.6)

7(1.6)

28.7

(2.6)

cyt/excl

cyt/excl

interpvalue(x,y)

(2.5e-2,97.6)

(2.5e-2,53.1)

(2.5e-2,60.8)

(2.5e-2,78.7)

R2

0.92

0.94

0.99

log 1

0(PC80)[mg/ml]

-1.44

-1.81

-1.68

-1.52

log 1

0(IC50)[mg/ml]

na-1.85

na-2.04

Table 136: Test item 1. Relative induction Yc with sample std in brackets(N=3) in three acceptedruns, R2 statistics, estimated log10(IC50) and log10(PC80) values and interpolated values for re-sponse at the concentration c8/2 (where appropriate). Highlighted in green values where Yc ≤ 80.

167

Citoxlab

Envigo

RISE

BDS

[mg/ml]run1

run5

run13

run5

run6

run7

run1

run4

run9

run1

run3

run4

1.5e-10

5e-10

1.5e-9

5e-9

1.5e-8

5e-8

1.5e-7

5e-7

1.5e-6

5e-6

1.5e-5

223(25.2)

215.5(4.5)165.8(29.3)

5e-5

198.1(15)

201.5(37.8)

161.5(23.6)

1.5e-4

232.3(23.8)180.1(32.2)

158.6(24.4)

5e-4

231.5(28.9)194.3(21.3)

157(13.6)

1.5e-3

230(38.9)

187.9(8.8)160.8(25.1)

5e-3

207.6(23.5)

142.1(4.5)147.2(29.3)

1.5e-2

141(12.2)

105.5(8.5)

99.8(13.1)

5e-2

18.7(2.1)

14.2(1.9)

12.6(1.1)

Table 137: Test item 1. Specificity control Sc. Relative induction with sample std in brackets(N=3).Highlighted in green values where Sn

c ≤ 80 where Snc = Sc/Sc1.

168

−12 −11 −10 −9 −8 −7 −6 −5 −4

0

20

40

60

80

100

120

140

160

180

200

220

240

260

280

300

320

340

360

380

400

420

440

460

480

log10(M)

Rela

tive Induction [%

]


Citoxlab

Envigo

RISE

BDS

Flutamide

Figure 153: Test item 1. Relative induction responses for accepted experiments in three participart-ing labs. Aggregated by laboratory and biological replicate.

169

D.2 Test item 2

−11 −10 −9 −8 −7 −6 −5

20

40

60

80

100

120

140

160

180

200

220

240

260

log10(M)

Re

lative

In

du

ctio

n [

%]


−11 −10 −9 −8 −7 −6 −5

20

40

60

80

100

120

140

160

180

200

220

log10(M)

Re

lative

In

du

ctio

n [

%]


−11 −10 −9 −8 −7 −6 −50

20406080

100120140160180200220240260280300320340360380400420440460480500520540560580600620640660680700720740760780800

log10(M)

Re

lative

In

du

ctio

n [

%]


−11 −10 −9 −8 −7 −6 −50

20

40

60

80

100

120

140

160

180

200

220

240

log10(M)

Re

lative

In

du

ctio

n [

%]


−11 −10 −9 −8 −7 −6 −50

20

40

60

80

100

120

140

160

180

200

220

log10(M)

Re

lative

In

du

ctio

n [

%]


−11 −10 −9 −8 −7 −6 −50

20

40

60

80

100

120

140

160

180

200

log10(M)

Re

lative

In

du

ctio

n [

%]


−11 −10 −9 −8 −7 −6 −5

20

40

60

80

100

120

140

160

180

log10(M)

Re

lative

In

du

ctio

n [

%]


−11 −10 −9 −8 −7 −6 −5

20

40

60

80

100

120

140

160

log10(M)

Re

lative

In

du

ctio

n [

%]


−11 −10 −9 −8 −7 −6 −50

20

40

60

80

100

120

140

160

180

log10(M)

Re

lative

In

du

ctio

n [

%]


−11 −10 −9 −8 −7 −6 −5

20

40

60

80

100

120

140

160

180

200

220

log10(M)

Re

lative

In

du

ctio

n [

%]


−11 −10 −9 −8 −7 −6 −50

20

40

60

80

100

120

140

160

180

200

log10(M)

Re

lative

In

du

ctio

n [

%]


−11 −10 −9 −8 −7 −6 −5

20

40

60

80

100

120

140

160

180

200

220

240

log10(M)

Re

lative

In

du

ctio

n [

%]




170

−11 −10 −9 −8 −7 −6 −50

20406080

100120140160180200220240260280300320340360380400420440460480500520540560580600620640660680700720740760780800

log10(M)

Re

lative

In

du

ctio

n [

%]

TI−CIT2XF, Citoxlab

run 4

run 13

run 15

Flutamide

−11 −10 −9 −8 −7 −6 −50

20

40

60

80

100

120

140

160

180

200

220

240

log10(M)

Re

lative

In

du

ctio

n [

%]

TI−ENV2XN, Envigo

run 1

run 2

run 4

Flutamide

−11 −10 −9 −8 −7 −6 −50

20

40

60

80

100

120

140

160

180

log10(M)

Re

lative

In

du

ctio

n [

%]

TI−10NM, RISE

run 1

run 7

run 9

Flutamide

−11 −10 −9 −8 −7 −6 −50

20

40

60

80

100

120

140

160

180

200

220

log10(M)

Re

lative

In

du

ctio

n [

%]

TI−BDS2GG, BDS

run 1

run 3

run 4

Flutamide


171

Citoxlab

Envigo

RISE

BDS

run4

run13

run15

run1

run2

run4

run1

run7

run9

run1

run3

run4

[µM]

[mg/ml]

PRE

PRE

PRE

PRE

PRE

PRE

PRE

PRE

PRE

PRE

PRE

PRE

1.52e-6

5e-10

96.7(1.6)105.4(12.2)90.6(14.4)

104.4(10.9)113.4(3)

108.8(2.5)

98.2(10.6)

95.7(2.9)102.3(6)

102.8(14.6)98.3(10.7)

94.9(0.8)

1.52e-5

5e-9

101.4(1.9)105.5(14.5)102.6(9.3)

112(16.2)

115.3(6.5)105.1(4.3)

108.2(10.5)96.3(9.4)

103(12)

101(14)

97.7(6.8)

93(3.1)

1.52e-4

5e-8

103.8(4.2)105.3(5.7)142.8(5.3)

118(9.9)117.2(7.6)120.2(5)

102.8(5.6)

93.4(7.1)106.6(2.8)

107(15.7)

101(14.5)

99.5(1.8)

1.52e-3

5e-7

165.6(5)

114.7(30.3)408.3(13)

148.8(16.4)122.6(11.5)136.8(6.6)

131.7(5.1)113.7(5.7)

139.1(19.2)138.4(16.7)128.3(8.1)126.6(3)

1.52e-2

5e-6

237.5(21.5)190.8(10.7)

775(74.1)

196.2(20.4)173.4(7.3)163.8(6.6)

172.5(7.9)138.4(7.3)

149(1.4)

179.1(20.1)151.5(12.6)185.5(9.8)

1.52e-1

5e-5

249.8(13.6)195.3(18.6)822.8(56.7)211.7(23.2)165.6(15)

181.6(12.3)173.9(10)

150.6(1.6)

153.1(1.1)

192.7(13)

161.8(15.5)186.7(5.5)

1.52

5e-4

265(13.9)

201.8(27.6)800.7(13.6)224.8(35.8)180.6(17.9)180.7(12)

186.6(1.9)172.4(5.1)

169.2(15.6)210.9(22.3)172.1(18.7)201.1(8.1)

15.22

5e-3

257.7(11)

213.6(8.4)712.7(30.2)241.5(18.9)211.5(14.5)194.5(12)

194.3(3.4)145.9(6.4)

177.6(5.7)

215.1(20.8)190.8(9.2)233.5(12.2)

R2

log 1

0(PC80)[mg/ml]

log 1

0(IC50)[mg/ml]


172

−11 −10 −9 −8 −7 −6 −50

20

40

60

80

100

120

140

160

180

200

220

240

260

280

300

320

340

360

380

400

420

440

460

480

500

520

540

560

580

600

620

640

660

680

700

720

740

760

780

800

log10(M)

Rela

tive Induction [%

]


Citoxlab

Envigo

RISE

BDS

Flutamide


173

D.3 Test item 3

−8 −7 −6 −5

20

40

60

80

100

120

140

160

180

200

220

240

260

280

300

320

log10(M)

Re

lative

In

du

ctio

n [

%]


−9 −8 −7 −6 −5

20

40

60

80

100

120

140

160

180

200

220

240

260

log10(M)

Re

lative

In

du

ctio

n [

%]


−9 −8 −7 −6 −50

20

40

60

80

100

120

140

160

180

200

220

240

260

log10(M)

Re

lative

In

du

ctio

n [

%]


−8 −7 −6 −5

20

40

60

80

100

120

140

160

180

200

log10(M)

Rela

tive Induction [%

]


−9 −8 −7 −6 −50

20

40

60

80

100

120

140

160

180

200

log10(M)

Rela

tive Induction [%

]


−9 −8 −7 −6 −50

20

40

60

80

100

120

140

160

180

200

220

log10(M)

Rela

tive Induction [%

]


−9 −8 −7 −6 −50

20

40

60

80

100

120

140

160

180

200

220

240

log10(M)

Rela

tive Induction [%

]


−9 −8 −7 −6 −50

20

40

60

80

100

120

140

160

180

200

log10(M)

Rela

tive Induction [%

]


−9 −8 −7 −6 −5

20

40

60

80

100

120

140

160

180

200

220

240

log10(M)

Rela

tive Induction [%

]


−8 −7 −6 −50

20

40

60

80

100

120

140

160

180

200

220

240

log10(M)

Re

lative

In

du

ctio

n [

%]


−8 −7 −6 −50

20

40

60

80

100

120

140

160

180

200

220

240

260

280

log10(M)

Rela

tive Induction [%

]


−8 −7 −6 −50

20

40

60

80

100

120

140

160

180

200

220

240

log10(M)

Rela

tive Induction [%

]




174

−8 −7 −6 −5

20

40

60

80

100

log10(M)

Re

lative

In

du

ctio

n*

[%]


−9 −8 −7 −6 −5

20

40

60

80

100

log10(M)R

ela

tive

In

du

ctio

n*

[%]


−9 −8 −7 −6 −50

20

40

60

80

100

log10(M)

Re

lative

In

du

ctio

n*

[%]


−8 −7 −6 −5

20

40

60

80

100

120

log10(M)

Rela

tive Induction*

[%]


−9 −8 −7 −6 −50

20

40

60

80

100

log10(M)

Rela

tive Induction*

[%]


−9 −8 −7 −6 −50

20

40

60

80

100

log10(M)

Rela

tive Induction*

[%]


−9 −8 −7 −6 −50

20

40

60

80

100

log10(M)

Rela

tive Induction*

[%]


−9 −8 −7 −6 −50

20

40

60

80

100

log10(M)

Rela

tive Induction*

[%]


−9 −8 −7 −6 −5

20

40

60

80

100

log10(M)

Rela

tive Induction*

[%]


−8 −7 −6 −50

20

40

60

80

100

log10(M)

Re

lative

In

du

ctio

n*

[%]


−8 −7 −6 −50

20

40

60

80

100

log10(M)

Rela

tive Induction*

[%]


−8 −7 −6 −50

20

40

60

80

100

log10(M)

Rela

tive Induction*

[%]





175

−9 −8 −7 −6 −50

20

40

60

80

100

120

140

160

180

200

220

240

260

280

300

320

log10(M)

Rela

tive Induction [%

]

TI−CIT2AE, Citoxlab

run 10

run 17

run 20

Flutamide

−9 −8 −7 −6 −50

20

40

60

80

100

120

140

160

180

200

log10(M)

Rela

tive Induction [%

]

TI−ENV2HD, Envigo

run 5

run 6

run 7

Flutamide

−9 −8 −7 −6 −50

20

40

60

80

100

120

140

160

180

200

220

240

log10(M)

Rela

tive Induction [%

]

TI−03HX, RISE

run 3

run 6

run 11

Flutamide

−8 −7 −6 −50

20

40

60

80

100

120

140

160

180

200

220

240

260

log10(M)

Rela

tive Induction [%

]

TI−BDS2CG, BDS

run 10

run 14

run 16

Flutamide


176

Citoxlab

Envigo

RISE

BDS

run10

run17

run20

run5

run6

run7

run3

run6

run11

run10

run14

run16

[µM]

[mg/ml]

COM

COM

COM

COM

COM

COM

COM

COM

COM

COM

COM

COM

3.24e-4

1.35e-7

98.6(5.7)105.5(13.8)94.8(1.9)

94(2.1)98.6(7.6)

4.61e-4

1.92e-7

94.2(9.2)96.9(5.8)

1.08e-3

4.5e-7

104.6(6.9)

91(9.2)

94(18.3)

89.7(7.4)94.3(1.8)95.9(3.6)

107.9(10.7)99.9(5.6)

2.3e-3

9.6e-7

92.6(7.4)95.2(1.6)

3.24e-3

1.35e-6

90.6(3.8)91.6(15.7)

85.2(7.7)90.7(3.4)89.4(8.3)

3.6e-3

1.5e-6

95.6(7.8)

94.8(7.8)

90.8(18.1)

1.08e-2

4.5e-6

81.1(9.4)

80.4(11.2)

76.6(9.8)

68(11.6)

73.4(4.5)

72.8(4.3)80.8(8.3)

74.1(3.7)89.8(11.9)

81.6(6.1)

1.15e-2

4.8e-6

71.3(1.4)

76(6.2)

3.24e-2

1.35e-5

60.8(2.6)

64.2(6.4)

56.1(0.1)

58.1(3.2)

61.3(3.3)

3.6e-2

1.5e-5

60.4(1.3)

61.2(7.8)

54.1(0.6)

66.1(3.8)

57.4(1.2)

5.76e-2

2.4e-5

48.3(5.4)

49(0.1)

1.08e-1

4.5e-5

40.7(2.3)

41.7(6.7)

40.2(7)

36.1(8.6)

34.9(2.3)

33.6(1)

35.1(1.9)

33.2(2.9)

41(4.1)

38.9(1.8)

2.88e-1

1.2e-4

20.7(2.9)

23.3(0.4)

3.24e-1

1.35e-4

26.1(3.5)

23.5(3.9)

23.3(2.4)

22(0.9)

23.4(1.7)

3.6e-1

1.5e-4

28.4(1.5)

21.2(2.2)

20.6(1.7)

26.4(3.2)

20.6(3.1)

1.08

4.5e-4

22.9(1.5)

20.4(2.1)

19.3(0.3)

14.6(2.4)

17.8(0.5)

18.4(1.3)

20.4(2.6)

18.4(1.3)

22.8(2)

19.6(2.8)

1.44

6e-4

16.2(2.1)

15.1(0.6)

3.6

1.5e-3

22.2(0.6)

18.3(1.1)

18.6(1.7)

23.9(1.1)

18.5(2.3)

7.2

3e-3

14.5(1.1)

15.9(1.2)

10.8

4.5e-3

22.2(0.3)

17.8(0.6)

36.01

1.5e-2

21.1(1)

13.3(1.6)

14.4(1)

16.8(0.6)

R2

0.38

0.5

0.43

0.48

0.46

0.38

0.53

0.55

0.38

0.4

0.39

0.5

log 1

0(PC80)[mg/ml]

-5.31

-5.59

-5.44

-5.33

-5.45

-5.62

-5.6

-5.55

-5.32

-5.09

-5.3

log 1

0(IC50)[mg/ml]

-4.79

-4.84

-4.82

-4.87

-4.76

-4.79

-4.84

-4.87

-4.82

na-4.8

-4.84


177

Citoxlab

Envigo

RISE

BDS

[mg/ml]

run10

run17

run20

run5

run6

run7

run3

run6

run11

run10

run14

run16

1.35e-7

194.8(9.1)189.9(21.8)233.8(10.6)

200(14)

231(14.7)

1.92e-7

249.7(5.5)

240.2(8.2)

4.5e-7

201.9(8.8)192.7(16.5)194.6(25.6)233.6(4.1)199.6(1.6)230.2(10.4)

250(29)

216.5(1.8)

9.6e-7

257.7(12.2)

252.8(7.9)

1.35e-6

186(15.3)

182.6(13.8)230.2(9)

197.4(1.7)240.5(6.8)

1.5e-6

193.1(19)

255.9(17.4)

213(6.8)

4.5e-6

307.2(4.7)

183.5(11.1)

181.7(19)

168.5(14)

232.1(14)

186.5(7.1)243.2(9)

237.4(9.1)

266.2(12.5)

231.8(16)

4.8e-6

237.1(22.6)

250.4(13.1)

1.35e-5

189.6(10.9)191.6(21.8)235.9(6.6)205.8(11.5)239.9(7.3)

1.5e-5

329.5(7.3)

195.4(16.9)

240.6(8.1)

256.3(26.3)

198.9(21.5)

2.4e-5

234.2(12.8)

261.1(5.3)

4.5e-5

320.4(9.6)

184.4(17.5)

196.2(7.1)188.1(18.9)235.4(7.3)191.1(9.6)

235(9.1)

226.4(11.7)

265.8(10.3)

204(19.1)

1.2e-4

231.1(6.8)

236.2(2.3)

1.35e-4

172.4(15.4)176.1(11.8)

205(6.1)179.7(9.4)221.6(4.4)

1.5e-4

297.7(11.1)

161.7(12.5)

212.4(23.8)

233.6(21.4)

196.1(4.2)

4.5e-4

272.8(14.5)

160.7(14.4)

150(7.3)160.4(7.5)

196.5(18.4)

172(6.5)185.2(3.3)

190.5(7.6)

210.3(10.2)

172.4(25.4)

6e-4

181.5(9.6)

191.8(6.9)

1.5e-3

150.2(4.1)

78.7(9.8)

121.3(4)

158.9(8.8)

111.3(11.1)

3e-3

53.1(4.6)

65.1(3.1)

4.5e-3

52.7(1.8)

45.7(1.3)

1.5e-2

28.4(1.3)

17.8

(2)

19(1.2)

22.7(1.2)



178

−9 −8 −7 −6 −50

20

40

60

80

100

120

140

160

180

200

220

240

260

280

300

320

log10(M)

Rela

tive Induction [%

]


Citoxlab

Envigo

RISE

BDS

Flutamide


179

D.4 Test item 4

−11 −10 −9 −8 −7 −6 −5

0

20

40

60

80

100

120

140

160

180

200

log10(M)

Rela

tive Induction [%

]TI−CIT2NX, run 1, Citoxlab

−11 −10 −9 −8 −7 −6 −5

20

40

60

80

100

120

log10(M)

Rela

tive Induction [%

]


−11 −10 −9 −8 −7 −6 −5

20

40

60

80

100

120

140

log10(M)

Rela

tive Induction [%

]


−11 −10 −9 −8 −7 −6 −50

20

40

60

80

100

log10(M)

Rela

tive Induction [%

]


−11 −10 −9 −8 −7 −6 −50

20

40

60

80

100

120

log10(M)

Rela

tive Induction [%

]


−11 −10 −9 −8 −7 −6 −50

20

40

60

80

100

120

log10(M)

Rela

tive Induction [%

]


−10 −9 −8 −7 −6 −50

20

40

60

80

100

120

140

160

180

200

220

log10(M)

Rela

tive Induction [%

]


−10 −9 −8 −7 −6 −5

20

40

60

80

100

120

140

160

180

200

log10(M)

Rela

tive Induction [%

]


−10 −9 −8 −7 −6 −5

20

40

60

80

100

120

140

160

180

200

220

240

log10(M)

Rela

tive Induction [%

]


−11 −10 −9 −8 −7 −6 −5

20

40

60

80

100

120

log10(M)

Re

lative

In

du

ctio

n [

%]


−11 −10 −9 −8 −7 −6 −50

20

40

60

80

100

log10(M)

Re

lative

In

du

ctio

n [

%]


−11 −10 −9 −8 −7 −6 −5

20

40

60

80

100

120

140

log10(M)

Re

lative

In

du

ctio

n [

%]




180

−11 −10 −9 −8 −7 −6 −5

0

20

40

60

80

100

120

140

160

180

200

log10(M)

Rela

tive Induction*

[%]


−11 −10 −9 −8 −7 −6 −5

20

40

60

80

100

120

log10(M)R

ela

tive Induction*

[%]


−11 −10 −9 −8 −7 −6 −5

20

40

60

80

100

120

140

log10(M)

Rela

tive Induction*

[%]


−11 −10 −9 −8 −7 −6 −50

20

40

60

80

100

log10(M)

Rela

tive Induction*

[%]


−11 −10 −9 −8 −7 −6 −50

20

40

60

80

100

120

log10(M)

Rela

tive Induction*

[%]


−11 −10 −9 −8 −7 −6 −50

20

40

60

80

100

120

log10(M)

Rela

tive Induction*

[%]


−10 −9 −8 −7 −6 −50

20

40

60

80

100

120

log10(M)

Rela

tive Induction*

[%]


−10 −9 −8 −7 −6 −5

20

40

60

80

100

log10(M)

Rela

tive Induction*

[%]


−10 −9 −8 −7 −6 −5

20

40

60

80

100

120

log10(M)

Rela

tive Induction*

[%]TI−01KX, run 11, RISE

−11 −10 −9 −8 −7 −6 −5

20

40

60

80

100

120

log10(M)

Re

lative

In

du

ctio

n*

[%]


−11 −10 −9 −8 −7 −6 −50

20

40

60

80

100

log10(M)

Re

lative

In

du

ctio

n*

[%]


−11 −10 −9 −8 −7 −6 −5

20

40

60

80

100

120

140

log10(M)

Re

lative

In

du

ctio

n*

[%]





181

−11 −10 −9 −8 −7 −6 −5

0

20

40

60

80

100

120

140

160

180

log10(M)

Rela

tive Induction [%

]

TI−CIT2NX, Citoxlab

run 1

run 5

run 13

Flutamide

−11 −10 −9 −8 −7 −6 −50

20

40

60

80

100

120

log10(M)

Rela

tive Induction [%

]

TI−ENV2ET, Envigo

run 1

run 2

run 4

Flutamide

−10 −9 −8 −7 −6 −50

20

40

60

80

100

120

140

160

180

200

220

240

log10(M)

Rela

tive Induction [%

]

TI−01KX, RISE

run 6

run 8

run 11

Flutamide

−11 −10 −9 −8 −7 −6 −50

20

40

60

80

100

120

log10(M)

Rela

tive Induction [%

]

TI−BDS2LN, BDS

run 1

run 3

run 4

Flutamide


182

Citoxlab

Envigo

RISE

BDS

run1

run5

run13

run1

run2

run4

run6

run8

run11

run1

run3

run4

[µM]

[mg/ml]

PRE

PRE

PRE

PRE

PRE

PRE

COM

COM

COM

PRE

PRE

PRE

1.29e-6

5e-10

140.1(12.8)116.6(6.4)

120.5(3.9)

96.9(6.2)103.6(2)

94.6(8.4)

3.88e-6

1.5e-9

102.2(11.7)98.8(3.3)111.9(4.1)

1.29e-5

5e-9

139(11.5)

86.4(1.7)128.5(5.4)

88.2(10.4)

102.1(16.2)102.5(1.4)

3.49e-5

1.35e-8

102.8(3.6)

81.5(3.6)

97.1(2)

3.88e-5

1.5e-8

101.3(8.4)

97.8(1.2)103.5(4.1)

1.16e-4

4.5e-8

97.6(3.1)

82.6(11.9)

93.2(1.8)

1.29e-4

5e-8

137.7(11.9)85.4(6.2)122.7(7.3)

89.3(4.8)124.5(12.9)94.3

(4)

3.49e-4

1.35e-7

118.2(5.4)

80.5(10)

92.5(2.5)

3.88e-4

1.5e-7

96.7(9.6)

96.3(3.8)97.9(0.6)

1.16e-3

4.5e-7

93.2(13.1)

82.7(5.6)

85.5(7.3)

1.29e-3

5e-7

136.2(4.8)

85.9(2.6)

120(7.5)92.1(8.5)

88.5(5.8)

94.8(6.4)

3.49e-3

1.35e-6

98.5(2.4)

76.7(5.1)

79.2(2.8)

3.88e-3

1.5e-6

96.2(10.7)

88.4(2.2)100.1(3.7)

1.16e-2

4.5e-6

86.3(2.7)

73.4(8.9)

79.8(0.8)

1.29e-2

5e-6

162.2(13.8)103.9(5.7)

122.1(9.3)

81.3(13.8)

91.9(3.6)

94.2(5.4)

3.49e-2

1.35e-5

88.1(3.9)

77.3(2.6)

86.6(11)

3.88e-2

1.5e-5

91(6.5)

81.8(4.6)100.1(6)

1.16e-1

4.5e-5

88(2.2)

70.2(2.1)

85.1(8.2)

1.29e-1

5e-5

177(9)

112.3(3.9)

122.2(4.9)

77.5(15.7)

87.9(6.7)

96.7(10.9)

3.88e-1

1.5e-4

95.2(5.1)

82.6(4.5)103.8(7)

1.29

5e-4

193.7(20.6)

127(9.9)130.2(1.5)

89.5(5.5)

90.5(4.2)109.6(9.6)

3.88

1.5e-3

111.3(6.2)102.7(1.9)

134.1(4.1)

12.94

5e-3

175.2(10.8)120.2(7.8)

137.4(3.8)

88.7(18.8)

102.2(7.6)128.6(10.2)

38.81

1.5e-2

116.6(7.6)

98(5.6)

140(5.3)

R2

0.38

0.03

0.33

log 1

0(PC80)[mg/ml]

-5.18

-6.09

-5.96

log 1

0(IC50)[mg/ml]

nana

-6.65


183

Citoxlab

Envigo

RISE

BDS

[mg/ml]run1

run5

run13

run1

run2

run4

run6

run8

run11

run1

run3

run4

5e-10

1.5e-9

5e-9

1.35e-8

209.3(10)

188.2(7.3)211.9(7.5)

1.5e-8

4.5e-8

217.7(9.2)201.2(13.7)220.6(11.5)

5e-8

1.35e-7

210.9(10)

182.9(12.5)220.9(5.9)

1.5e-7

4.5e-7

227.7(11)

189.4(2.8)225.2(16.7)

5e-7

1.35e-6

208.7(7.6)192.9(7.5)229.1(14.7)

1.5e-6

4.5e-6

226.5(10.2)189.4(12.8)243.7(12.8)

5e-6

1.35e-5

226(8.3)206.8(4.8)224.7(10.6)

1.5e-5

4.5e-5

212.8(13.3)196.4(1.5)204.4(13.6)

5e-5

1.5e-4

5e-4

1.5e-3

5e-3

1.5e-2



184

−11 −10 −9 −8 −7 −6 −5

0

20

40

60

80

100

120

140

160

180

200

220

240

log10(M)

Rela

tive Induction [%

]


Citoxlab

Envigo

RISE

BDS

Flutamide


185

D.5 Test item 5

−8 −7 −6 −50

20

40

60

80

100

120

140

160

180

200

220

240

260

280

log10(M)

Re

lative

In

du

ctio

n [

%]


−8 −7 −6 −50

20

40

60

80

100

120

140

160

180

200

220

240

260

280

300

320

340

log10(M)

Re

lative

In

du

ctio

n [

%]


−8 −7 −6 −50

20

40

60

80

100

120

140

160

180

200

220

240

260

log10(M)

Re

lative

In

du

ctio

n [

%]


−8 −7 −6 −5

20

40

60

80

100

120

140

160

180

200

220

240

log10(M)

Re

lative

In

du

ctio

n [

%]


−8 −7 −6 −50

20

40

60

80

100

120

140

160

180

200

220

log10(M)

Re

lative

In

du

ctio

n [

%]


−8 −7 −6 −50

20

40

60

80

100

120

140

160

180

log10(M)

Re

lative

In

du

ctio

n [

%]


−8 −7 −6 −50

20

40

60

80

100

120

140

160

180

200

220

240

log10(M)

Re

lative

In

du

ctio

n [

%]


−8 −7 −6 −50

20

40

60

80

100

120

140

160

180

200

220

log10(M)

Re

lative

In

du

ctio

n [

%]


−8 −7 −6 −50

20

40

60

80

100

120

140

160

180

200

220

log10(M)

Re

lative

In

du

ctio

n [

%]


−8 −7 −6 −5

20

40

60

80

100

120

140

160

180

200

220

240

260

log10(M)

Re

lative

In

du

ctio

n [

%]


−8 −7 −6 −50

20

40

60

80

100

120

140

160

180

200

220

240

260

log10(M)

Re

lative

In

du

ctio

n [

%]


−8 −7 −6 −50

20

40

60

80

100

120

140

160

180

200

220

240

260

280

300

log10(M)

Re

lative

In

du

ctio

n [

%]




186

−8 −7 −6 −50

20

40

60

80

100

log10(M)

Re

lative

In

du

ctio

n*

[%]


−8 −7 −6 −50

20

40

60

80

100

log10(M)R

ela

tive

In

du

ctio

n*

[%]


−8 −7 −6 −50

20

40

60

80

100

log10(M)

Re

lative

In

du

ctio

n*

[%]


−8 −7 −6 −5

20

40

60

80

100

120

log10(M)

Re

lative

In

du

ctio

n*

[%]


−8 −7 −6 −50

20

40

60

80

100

log10(M)

Re

lative

In

du

ctio

n*

[%]


−8 −7 −6 −50

20

40

60

80

100

120

log10(M)

Re

lative

In

du

ctio

n*

[%]


−8 −7 −6 −50

20

40

60

80

100

log10(M)

Re

lative

In

du

ctio

n*

[%]


−8 −7 −6 −50

20

40

60

80

100

log10(M)

Re

lative

In

du

ctio

n*

[%]


−8 −7 −6 −50

20

40

60

80

100

log10(M)

Re

lative

In

du

ctio

n*

[%]


−8 −7 −6 −5

20

40

60

80

100

log10(M)

Re

lative

In

du

ctio

n*

[%]


−8 −7 −6 −50

20

40

60

80

100

log10(M)

Re

lative

In

du

ctio

n*

[%]


−8 −7 −6 −50

20

40

60

80

100

120

log10(M)

Re

lative

In

du

ctio

n*

[%]





187

−8 −7 −6 −50

20

40

60

80

100

120

140

160

180

200

220

240

260

280

300

320

log10(M)

Rela

tive Induction [%

]

TI−CIT2RD, Citoxlab

run 7

run 9

run 16

Flutamide

−8 −7 −6 −50

20

40

60

80

100

120

140

160

180

200

220

log10(M)

Rela

tive Induction [%

]

TI−ENV2YA, Envigo

run 5

run 6

run 7

Flutamide

−8 −7 −6 −50

20

40

60

80

100

120

140

160

180

200

220

log10(M)

Rela

tive Induction [%

]

TI−05MZ, RISE

run 3

run 5

run 11

Flutamide

−8 −7 −6 −50

20

40

60

80

100

120

140

160

180

200

220

240

260

280

log10(M)

Rela

tive Induction [%

]

TI−BDS2CW, BDS

run 8

run 11

run 13

Flutamide


188

Citoxlab

Envigo

RISE

BDS

run7

run9

run16

run5

run6

run7

run3

run5

run11

run8

run11

run13

[µM]

[mg/ml]

COM

COM

COM

COM

COM

COM

COM

COM

COM

COM

COM

COM

1.97e-2

4.5e-6

98.4(4.5)

98(2.9)

98(3.7)102.6(5.8)

102(3.3)92.6(20.6)

94.7(2.8)102.8(3.1)

93.1(1.5)91.5(2.3)112.2(2.6)

119.1(7.7)

6.57e-2

1.5e-5

90.5(2.4)90.7(5)

88.7(2.2)108.1(13.5)98.2(7.7)96.3(17.9)

88.5(5)

102.2(1.7)

88.8(6.1)96.8(1.9)

115(2.9)116.2(9.8)

1.97e-1

4.5e-5

88.1(6.3)86.3(7.8)

79.4(3.5)

94.4(14.4)

81.5(3.6)95.1(13.7)

81.5(3.5)89.8(6)

83.9(4.3)85.6(6.5)104.3(3)

106(6.5)

6.57e-1

1.5e-4

66.5(1.8)

64.5(1.4)

70.1(4.1)

80.2(12.5)

68(3.8)84.2(20)

62.5(2.3)

74.3(8.6)

64(2.8)

71(3.2)

80(2.9)82.6(2.5)

1.97

4.5e-4

40.8(1.4)

32.3(0.7)

36.7(3.2)

43.2(4.9)

40.4(3.7)

40.3(6.6)

36.9(2)

37.9(3.7)

35.4(1.8)

38.9(3.2)

48.4(1.1)

48.4(2.7)

6.57

1.5e-3

12.1(0.3)

10.6(0.5)

11.7(1)

12.9(1)

11.2(1.1)

10.4(1.5)

11.8(1)

12.3(0.8)

10.6(1.6)

12.8(1.4)

15.4(1.2)

15.8(0.4)

19.71

4.5e-3

2(0.2)

2(0.3)

1.9(0.1)

3.6(0.4)

2.7(0.3)

20.3(2.3)

3.7(0.6)

3.1(0.7)

1.9(0.4)

3.9(0.6)

5(0.5)

4.4(0)

65.7

1.5e-2

0(0.1)

0(0.1)

-0.2(0.1)

0.9(0.3)

0.8(0.6)

-0.1(1.2)

0.7(0.2)

0.1(0.4)

0.3(0.6)

2.3(0.1)

2.1(0.3)

2.4(0.3)

R2

0.21

0.37

0.35

0.28

0.28

0.32

0.41

0.3

0.3

0.32

0.25

0.36

log 1

0(PC80)[mg/ml]

-4.1

-4.13

-4.4

-3.82

-4.29

-3.76

-4.29

-3.95

-4.2

-4.08

-3.82

-3.78

log 1

0(IC50)[mg/ml]

-3.48

-3.58

-3.48

-3.46

-3.54

-3.45

-3.53

-3.52

-3.52

-3.47

-3.49

-3.51


189

Citoxlab

Envigo

RISE

BDS

[mg/ml]

run7

run9

run16

run5

run6

run7

run3

run5

run11

run8

run11

run13

4.5e-6

263.6(3.6)335.9(8.6)240.5(8.6)

201.1(2.6)201.9(4.2)

157(17.7)

221.3(11.3)

228(2.8)216.9(1.3)

221.4(17.9)

247.4(4.7)

275.2(6.7)

1.5e-5

269.1(7.2)322.8(12.7)239.5(11.6)216.4(20.8)192.6(30.5)171.6(24.1)239.2(9.4)217.7(5.2)

213.7(8.9)

229(9.9)

253.6(6.2)

283.9(7.1)

4.5e-5

272.4(24.8)

335(17.1)

256.6(6)

223.8(15.6)194.5(29.4)162.2(19)

223.1(8.8)221.5(4.4)

220.7(4.9)

212(15.6)

255.4(9.9)

269.6(21)

1.5e-4

285.8(14.5)

319.7(13.5)

246(10.6)

214.6(11)

198.8(7.7)163.3(25.1)231.8(6.3)221.6(4.5)

228.8(10)

232.1(26.2)

249.9(10.1)

295.2(8)

4.5e-4

279.7(20)

318.8(10.1)241.9(21.4)221.1(33.5)201.1(16.7)145.4(6.9)

220.4(4.1)228.1(6.6)

227.2(3.9)

229.3(28.8)

273.4(4.2)

277(4.6)

1.5e-3

289.9(6.8)317.8(9.9)241.3(5.6)

209.5(22.9)193.8(9.1)172.4(17)

217(9.5)223.4(9)

216.6(5.4)

216.6(9.2)

255.4(8.8)

273(12.7)

4.5e-3

254(10.7)

272.4(7.2)209.2(2.7)

199.1(30.8)183.5(10)

150.8(7.7)

191.9(3.9)195.9(4.2)

194.6(2.4)

205.6(7.8)

234.3(7.5)

246.7(10.6)

1.5e-2

106.8(7.6)

85.9(3.9)

80.6(5.4)

80.4(4.8)

68.6(5.9)

59.1(4.2)

81.8(2.9)

72.4(1.2)

95.9(3.7)

122.2(6.5)

143.8(1.2)

150.4(10.4)



190

−8 −7 −6 −50

20

40

60

80

100

120

140

160

180

200

220

240

260

280

300

320

log10(M)

Rela

tive Induction [%

]


Citoxlab

Envigo

RISE

BDS

Flutamide


191

D.6 Test item 6

−8 −7 −6 −5

20

40

60

80

100

120

140

160

180

200

220

240

260

280

300

log10(M)

Rela

tive Induction [%

]TI−CIT2YY, run 7, Citoxlab

−8 −7 −6 −50

20

40

60

80

100

120

140

160

180

200

220

240

260

280

300

log10(M)

Rela

tive Induction [%

]


−8 −7 −6 −50

20

40

60

80

100

120

140

160

180

200

220

240

log10(M)

Rela

tive Induction [%

]


−8 −7 −6 −5

20

40

60

80

100

120

140

160

180

200

220

240

log10(M)

Rela

tive Induction [%

]


−8 −7 −6 −50

20

40

60

80

100

120

140

160

180

200

220

240

log10(M)

Rela

tive Induction [%

]TI−ENV2DF, run 6, Envigo

−8 −7 −6 −50

20

40

60

80

100

120

140

160

180

200

220

240

log10(M)

Rela

tive Induction [%

]


−8 −7 −6 −50

20

40

60

80

100

120

140

160

180

200

220

log10(M)

Rela

tive Induction [%

]


−8 −7 −6 −5

20

40

60

80

100

120

140

160

180

200

log10(M)

Rela

tive Induction [%

]


−8 −7 −6 −50

20

40

60

80

100

120

140

160

180

200

220

240

log10(M)

Rela

tive Induction [%

]


−8 −7 −6 −50

20

40

60

80

100

120

140

160

180

200

220

240

260

280

log10(M)

Rela

tive Induction [%

]


−8 −7 −6 −5

20

40

60

80

100

120

140

160

180

200

220

log10(M)

Rela

tive Induction [%

]


−8 −7 −6 −50

20

40

60

80

100

120

140

160

180

200

220

240

260

log10(M)

Rela

tive Induction [%

]




192

−8 −7 −6 −5

20

40

60

80

100

log10(M)

Rela

tive Induction*

[%]


−8 −7 −6 −50

20

40

60

80

100

120

log10(M)R

ela

tive Induction*

[%]


−8 −7 −6 −50

20

40

60

80

100

log10(M)

Rela

tive Induction*

[%]


−8 −7 −6 −5

20

40

60

80

100

120

log10(M)

Rela

tive Induction*

[%]


−8 −7 −6 −50

20

40

60

80

100

120

log10(M)

Rela

tive Induction*

[%]


−8 −7 −6 −50

20

40

60

80

100

120

140

160

log10(M)

Rela

tive Induction*

[%]


−8 −7 −6 −50

20

40

60

80

100

log10(M)

Rela

tive Induction*

[%]


−8 −7 −6 −5

20

40

60

80

100

log10(M)

Rela

tive Induction*

[%]


−8 −7 −6 −50

20

40

60

80

100

log10(M)

Rela

tive Induction*

[%]TI−07WS, run 10, RISE

−8 −7 −6 −50

20

40

60

80

100

log10(M)

Rela

tive Induction*

[%]


−8 −7 −6 −5

20

40

60

80

100

log10(M)

Rela

tive Induction*

[%]


−8 −7 −6 −50

20

40

60

80

100

log10(M)

Rela

tive Induction*

[%]





193

−8 −7 −6 −50

20

40

60

80

100

120

140

160

180

200

220

240

260

280

log10(M)

Rela

tive Induction [%

]

TI−CIT2YY, Citoxlab

run 7

run 11

run 16

Flutamide

−8 −7 −6 −50

20

40

60

80

100

120

140

160

180

200

220

log10(M)

Rela

tive Induction [%

]

TI−ENV2DF, Envigo

run 5

run 6

run 7

Flutamide

−8 −7 −6 −50

20

40

60

80

100

120

140

160

180

200

220

log10(M)

Rela

tive Induction [%

]

TI−07WS, RISE

run 5

run 8

run 10

Flutamide

−8 −7 −6 −50

20

40

60

80

100

120

140

160

180

200

220

240

260

log10(M)

Rela

tive Induction [%

]

TI−BDS2QX, BDS

run 5

run 7

run 9

Flutamide


194

Citoxlab

Envigo

RISE

BDS

run7

run11

run16

run5

run6

run7

run5

run8

run10

run5

run7

run9

[µM]

[mg/ml]

COM

COM

COM

COM

COM

COM

COM

COM

COM

COM

COM

COM

1.05e-3

4.5e-7

93.3(1.6)

98.9(2.9)

102(6.6)112.8(10.7)99.5(19.9)

99.7(9.9)

101.8(4.6)

99(7.9)98.9(2.4)

92.4(6.4)

98(1.8)98.3(2.3)

3.49e-3

1.5e-6

87.5(4.8)

99.7(3.3)98.4(5.7)

102(6)

103.5(11.9)96.7(13.2)

99.7(2.5)

93(7.5)94.3(5.2)

83.3(1.6)91.3(8.7)92.7(4.3)

1.05e-2

4.5e-6

81.5(7.5)

91.6(8.8)85.9(4)

102(12.2)

101.2(7.5)122.3(50)

89.3(9.6)87.4(5.2)109.7(9.7)

76.4(3.4)82.7(2.3)82.7(3.6)

3.49e-2

1.5e-5

78(10.9)

83(4.1)

74.5(3.5)

92.4(6.2)

92(7.9)

86.7(8.8)

77.3(3.9)

71.3(3.3)

77.7(5.9)

58(1)

65.7(1.3)

68.9(3.2)

1.05e-1

4.5e-5

53.1(5.6)

56.6(4.5)

44.8(1.2)

66.6(5)

58.3(7.6)

62.7(6.9)

47.6(4.1)

46.9(1.7)

72.2(29.8)

33.2(1.3)

42.8(1.9)

46.4(5.4)

3.49e-1

1.5e-4

21(1.4)

20.9(0.6)

19(0.9)

26.7(0.3)

25.6(1.6)

25.7(6.6)

18.5(0.6)

18.3(2.3)

32.5(1.1)

11.6(1.3)

13.8(0.6)

12.8(1.2)

1.05

4.5e-4

4.6(0.8)

5.2(0.6)

4.7(0.7)

7(1.5)

6.2(0.7)

5.5(0.1)

4.9(1)

3.9(0.6)

6.9(2.4)

3.6(0.2)

3.4(0.1)

3.8(0.4)

3.49

1.5e-3

1(0.1)

1.5(0.3)

1.4(0.3)

2.6(0.2)

1.7(0.3)

0.6(0.9)

2(0)

1.8(0.4)

1.7(0.4)

2(0.3)

1.4(0.2)

1.9(0.2)

R2

0.63

0.42

0.48

0.21

0.17

0.61

0.63

0.58

0.59

0.1

0.4

0.45

log 1

0(PC80)[mg/ml]

-4.92

-4.74

-4.99

-4.55

-4.63

-4.72

-4.89

-5.06

-4.87

-5.54

-5.24

-5.23

log 1

0(IC50)[mg/ml]

-4.21

-4.25

-4.42

-4.19

-4.23

-4.22

-4.39

-4.38

-4.05

-4.6

-4.47

-4.42


195

Citoxlab

Envigo

RISE

BDS

[mg/ml]

run7

run11

run16

run5

run6

run7

run5

run8

run10

run5

run7

run9

4.5e-7

284.9(13)

293.3(15.6)

244.1(8.1)

220.5(23.4)

203(8.2)179.2(13.6)216.4(7.5)189.2(12.5)219.8(8.8)

252.4(1.9)

209.2(15)

226.2(15.2)

1.5e-6

272.1(9.4)

288.4(12.3)

234.1(2.2)

217.9(29.3)

200.4(55.9)185.1(21.1)

214

(9)

200.1(7.2)

230.5(10.7)

233.5(26.7)

201.7(6.1)

242.2(20.3)

4.5e-6

288.6(7.5)

271.6(14.1)

235.4(8.2)

201.2(17.4)

221.8(10.3)

203(46)

214.8(13.2)

195(11.2)

226.5(17.4)

233.2(3.2)

204.8(8.5)

230.7(22)

1.5e-5

292.4(11.9)

279(3.5)

235.8(14.3)

222.7(24.7)

219.4(11)

171.1(21.6)211.4(7.9)

188(13.6)

232.7(7.8)

237.3(14.9)

203.8(7.2)

234.3(14.7)

4.5e-5

282.2(9.5)

288.5(4.3)

229.2(4.3)

212.7(32.2)

209.3(12.7)

177(20.7)

210.1(8.8)185.7(4.9)

207.8(6.7)

274.4(7.4)

198.5(7.6)

237.7(9.7)

1.5e-4

262(22.6)

275.7(11.1)

230.9(2.2)

228(31)

208.2(4.9)179.3(14.8)

198(18.6)

185.8(16.4)214.8(8.5)

247.5(6.2)

205.3(18.1)

218.3(11.3)

4.5e-4

257.6(6.5)

273(1.7)

222.8(10.4)

211(20.6)

217.2(10.5)169.2(17.8)

190(6.8)180.6(8.4)

203.4(9.9)

237.9(11.1)

191.9(4.1)

219.9(11.6)

1.5e-3

209.9(7)

218.5(21.6)

173.8(6)

161.6(16.9)172.8(15.5)150.6(20.9)

149.4(1.8)154.7(9.1)

157.8(15.1)

173.8(7.3)

154.5(5.6)

172.4(10)



196

−8 −7 −6 −50

20

40

60

80

100

120

140

160

180

200

220

240

260

280

log10(M)

Rela

tive Induction [%

]


Citoxlab

Envigo

RISE

BDS

Flutamide


197

D.7 Test item 7

−11 −10 −9 −8 −7 −6 −50

20

40

60

80

100

log10(M)

Rela

tive Induction [%

]TI−CIT2RK, run 5, Citoxlab

−11 −10 −9 −8 −7 −6 −50

20

40

60

80

100

log10(M)

Rela

tive Induction [%

]


−12 −11 −10 −9 −8 −7 −6 −50

20

40

60

80

100

log10(M)

Rela

tive Induction [%

]


−11 −10 −9 −8 −7 −6 −50

20

40

60

80

100

120

140

log10(M)

Rela

tive Induction [%

]


−12 −11 −10 −9 −8 −7 −6 −50

20

40

60

80

100

120

140

log10(M)

Rela

tive Induction [%

]TI−ENV2VZ, run 2, Envigo

−12 −11 −10 −9 −8 −7 −6 −50

20

40

60

80

100

120

140

log10(M)

Rela

tive Induction [%

]


−11 −10 −9 −8 −7 −6 −50

20

40

60

80

100

log10(M)

Rela

tive Induction [%

]


−12 −11 −10 −9 −8 −7 −6 −50

20

40

60

80

100

log10(M)

Rela

tive Induction [%

]


−12 −11 −10 −9 −8 −7 −6 −5

20

40

60

80

100

log10(M)

Rela

tive Induction [%

]


−11 −10 −9 −8 −7 −6 −50

20

40

60

80

100

log10(M)

Rela

tive Induction [%

]


−11 −10 −9 −8 −7 −6 −50

20

40

60

80

100

log10(M)

Rela

tive Induction [%

]


−11 −10 −9 −8 −7 −6 −50

20

40

60

80

100

log10(M)

Rela

tive Induction [%

]




198

−12 −11 −10 −9 −8 −7 −6 −50

20

40

60

80

100

log10(M)

Rela

tive Induction [%

]

TI−CIT2RK, Citoxlab

run 5

run 14

run 15

Flutamide

−12 −11 −10 −9 −8 −7 −6 −50

20

40

60

80

100

120

140

log10(M)

Rela

tive Induction [%

]

TI−ENV2VZ, Envigo

run 1

run 2

run 4

Flutamide

−12 −11 −10 −9 −8 −7 −6 −50

20

40

60

80

100

log10(M)

Rela

tive Induction [%

]

TI−09YP, RISE

run 1

run 4

run 7

Flutamide

−11 −10 −9 −8 −7 −6 −50

20

40

60

80

100

log10(M)

Rela

tive Induction [%

]

TI−BDS2MU, BDS

run 1

run 3

run 4

Flutamide


199

Citoxlab

Envigo

RISE

BDS

run5

run14

run15

run1

run2

run4

run1

run4

run7

run1

run3

run4

[µM]

[mg/ml]

PRE

PRE

PRE

PRE

PRE

PRE

PRE

PRE

PRE

PRE

PRE

PRE

1.69e-7

5e-11

103.2(4.6)

92.1(7.4)

4.55e-7

1.35e-10

93.1(9.9)

5.06e-7

1.5e-10

98.6(6.1)100.4(2.3)

1.52e-6

4.5e-10

94.4(5.3)

1.69e-6

5e-10

108.6(6.9)

97.7(6.6)98.1(9.6)

4.55e-6

1.35e-9

92.3(8.5)

5.06e-6

1.5e-9

91.4(8.2)

103.6(15.3)99.4(1.1)106.3(14.9)

101.6(2.7)92.7(6.4)98.4(7.9)

1.52e-5

4.5e-9

93(1.3)

1.69e-5

5e-9

104.7(9)

95.9(1)

92.4(1.4)

4.55e-5

1.35e-8

93.4(17.6)

5.06e-5

1.5e-8

95.9(7.7)

104(10.9)

81.3(12.7)

104(4.8)

101.3(6.4)91.2(8.5)101.4(11.6)

1.52e-4

4.5e-8

99.1(6.2)

1.69e-4

5e-8

106.2(4.4)

104.1(2.7)

92.8(7.3)

4.55e-4

1.35e-7

95.2(9.5)

5.06e-4

1.5e-7

99.6(5.7)

109.5(20.6)96.5(6.4)101.1(6)

99.5(6.3)94.7(9.1)98.2

(6)

1.52e-3

4.5e-7

95.9(8.3)

1.69e-3

5e-7

102.5(4.4)

100.5(3.8)

91.5(2.7)

4.55e-3

1.35e-6

90.1(2.9)

5.06e-3

1.5e-6

93.8(6.7)

117.9(15.1)83.4(18.3)

101.8(2.4)

100.6(7.3)90.4(7.9)101.5(11.2)

1.52e-2

4.5e-6

99(8.2)

1.69e-2

5e-6

103.8(4.9)

101.4(2.5)

91.9(11.5)

4.55e-2

1.35e-5

91.6(5.5)

5.06e-2

1.5e-5

95.7(5.1)

111.6(14.7)94.2(7.7)140.7(4.7)

96.8(5.8)86.6(8)

102.7(14.4)

1.52e-1

4.5e-5

95.9(12.9)

1.69e-1

5e-5

104(4)

101.1(1.6)

91.7(6.9)

4.55e-1

1.35e-4

84.1(6.7)

5.06e-1

1.5e-4

96(8.2)

110.9(18.1)93.5(5.2)102.4(5.8)

91.6(2.9)88.4(6.1)94.7(10.2)

1.52

4.5e-4

93.5(7.7)

1.69

5e-4

101.8(0.5)

107.4(2.3)

87.8(6.2)

4.55

1.35e-3

85.5(15.6)

5.06

1.5e-3

100.5(11.2)

134.2(27)

124.5(17.5)111.6(8.4)

98.5(10.6)

87.1(7.9)98.1(15.1)

15.18

4.5e-3

cyt/excl

16.86

5e-3

cyt/excl

50.59

1.5e-2

cyt/excl

cyt/excl

cyt/excl

cyt/excl

cyt/excl

R2

log 1

0(PC80)[mg/ml]

log 1

0(IC50)[mg/ml]


200

−12 −11 −10 −9 −8 −7 −6 −50

20

40

60

80

100

120

140

log10(M)

Rela

tive Induction [%

]


Citoxlab

Envigo

RISE

BDS

Flutamide


201

D.8 Test item 8

−11 −10 −9 −8 −7 −6 −50

20

40

60

80

100

log10(M)

Rela

tive Induction [%

]TI−CIT2XK, run 5, Citoxlab

−12 −11 −10 −9 −8 −7 −6 −50

20

40

60

80

100

120

log10(M)

Rela

tive Induction [%

]


−12 −11 −10 −9 −8 −7 −6 −50

20

40

60

80

100

120

log10(M)

Rela

tive Induction [%

]


−11 −10 −9 −8 −7 −6 −50

20

40

60

80

100

log10(M)

Rela

tive Induction [%

]


−12 −11 −10 −9 −8 −7 −6 −50

20

40

60

80

100

log10(M)

Rela

tive Induction [%

]TI−ENV2QF, run 2, Envigo

−12 −11 −10 −9 −8 −7 −6 −50

20

40

60

80

100

log10(M)

Rela

tive Induction [%

]


−11 −10 −9 −8 −7 −6 −50

20

40

60

80

100

log10(M)

Rela

tive Induction [%

]


−12 −11 −10 −9 −8 −7 −6 −50

20

40

60

80

100

log10(M)

Rela

tive Induction [%

]


−12 −11 −10 −9 −8 −7 −6 −50

20

40

60

80

100

log10(M)

Rela

tive Induction [%

]


−11 −10 −9 −8 −7 −6 −50

20

40

60

80

100

log10(M)

Rela

tive Induction [%

]


−11 −10 −9 −8 −7 −6 −50

20

40

60

80

100

log10(M)

Rela

tive Induction [%

]


−11 −10 −9 −8 −7 −6 −50

20

40

60

80

100

log10(M)

Rela

tive Induction [%

]




202

−12 −11 −10 −9 −8 −7 −6 −50

20

40

60

80

100

120

log10(M)

Rela

tive Induction [%

]

TI−CIT2XK, Citoxlab

run 5

run 12

run 15

Flutamide

−12 −11 −10 −9 −8 −7 −6 −50

20

40

60

80

100

log10(M)

Rela

tive Induction [%

]

TI−ENV2QF, Envigo

run 1

run 2

run 4

Flutamide

−12 −11 −10 −9 −8 −7 −6 −50

20

40

60

80

100

log10(M)

Rela

tive Induction [%

]

TI−06NS, RISE

run 1

run 2

run 4

Flutamide

−11 −10 −9 −8 −7 −6 −50

20

40

60

80

100

log10(M)

Rela

tive Induction [%

]

TI−BDS2WW, BDS

run 2

run 3

run 4

Flutamide


203

Citoxlab

Envigo

RISE

BDS

run5

run12

run15

run1

run2

run4

run1

run2

run4

run2

run3

run4

[µM]

[mg/ml]

PRE

PRE

PRE

PRE

PRE

PRE

PRE

PRE

PRE

PRE

PRE

PRE

1.35e-7

5e-11

98.3(6)

103.7(7)

4.04e-7

1.5e-10

111.4(3.6)

89(6.8)

95.9(8.1)

95.9(8.6)

1.35e-6

5e-10

89.5(3.4)

100.4(11.3)108.4(6.6)

102.2(7.1)

4.04e-6

1.5e-9

109.8(6.3)

100.6(7.8)

96.3

(7.5)

98.9(5.4)101.4(11.1)

99.9(4.9)90.2

(2.9)

101.5(2)

1.35e-5

5e-9

89.2(5.2)

100.9(10.6)98.1(6.2)95.9(2.7)

4.04e-5

1.5e-8

112.7(7.2)

98.3(11.6)

106.5(5.2)

106.3(10.4)95.4(18.1)

98.4(1.5)96.3

(0.5)

100.8(1.6)

1.35e-4

5e-8

80.9(3.2)

97.7(4.4)

93.7(1.7)

97(5.2)

4.04e-4

1.5e-7

110.1(5.2)

100.9(1.3)

95.4(11.5)

99.4(4.9)108.3(6.3)

98.3(7.9)94.3

(2.9)

99.9(5.2)

1.35e-3

5e-7

88.9(7.3)

99(9)

106(2.1)95.6(5.5)

4.04e-3

1.5e-6

114.8(5.4)

92.2(5.8)

98.9

(8.2)

106(7)

99.5

(5)

99.5(3.8)93.2

(8.2)

102.5(3.6)

1.35e-2

5e-6

85.2(3.3)

102.4(3.9)

102(7.6)93.9(4.8)

4.04e-2

1.5e-5

113.2(1.4)

108.4(17.1)

98.8(10.6)

102.9(4.4)101.4(5.1)

96.1(3.3)94.2

(9.4)

102.8(4.9)

1.35e-1

5e-5

85.1(2.9)

96.9(1.4)103.4(4.6)

93.3(8.5)

4.04e-1

1.5e-4

121.8(1.5)

103.9(2.2)

101.7(11.2)

99.9(4.4)103.8(0.9)

97.4(1.4)98.6

(3.6)

108(3)

1.35

5e-4

101.6(6)

98.2(4.4)104.3(7.4)

100.9(6.1)

4.04

1.5e-3

82.4(5.3)82.8(5.9)

77.2(0.9)

89.8(7.8)

80.3(2.2)

85.8(1.8)

76.7

(4)

96(2.2)

13.46

5e-3

cyt/excl

cyt/excl

40.38

1.5e-2

cyt/excl

cyt/excl

cyt/excl

cyt/excl

interpvalue(x,y)

(7.5e-4,84.6)

(7.5e-4,83.3)

R2

log 1

0(PC80)[mg/ml]

-2.88

-2.9

log 1

0(IC50)[mg/ml]

-2.87

-2.74


204

−12 −11 −10 −9 −8 −7 −6 −50

20

40

60

80

100

120

log10(M)

Rela

tive Induction [%

]


Citoxlab

Envigo

RISE

BDS

Flutamide


205

D.9 Test item 9

−11 −10 −9 −8 −7 −6 −5

20

40

60

80

100

log10(M)

Re

lative

In

du

ctio

n [

%]


−11 −10 −9 −8 −7 −6 −5

20

40

60

80

100

120

log10(M)

Re

lative

In

du

ctio

n [

%]


−11 −10 −9 −8 −7 −6 −50

20

40

60

80

100

log10(M)

Re

lative

In

du

ctio

n [

%]


−11 −10 −9 −8 −7 −6 −50

20

40

60

80

100

120

140

log10(M)

Re

lative

In

du

ctio

n [

%]


−11 −10 −9 −8 −7 −6 −50

20

40

60

80

100

120

log10(M)

Re

lative

In

du

ctio

n [

%]


−11 −10 −9 −8 −7 −6 −50

20

40

60

80

100

log10(M)

Re

lative

In

du

ctio

n [

%]


−8 −7 −6 −50

20

40

60

80

100

120

140

160

180

200

220

240

log10(M)

Re

lative

In

du

ctio

n [

%]


−8 −7 −6 −5

20

40

60

80

100

120

140

160

180

200

220

log10(M)

Re

lative

In

du

ctio

n [

%]


−8 −7 −6 −5

20

40

60

80

100

120

140

160

180

200

220

240

log10(M)

Re

lative

In

du

ctio

n [

%]


−11 −10 −9 −8 −7 −6 −50

20

40

60

80

100

log10(M)

Re

lative

In

du

ctio

n [

%]


−11 −10 −9 −8 −7 −6 −50

20

40

60

80

100

log10(M)

Re

lative

In

du

ctio

n [

%]


−11 −10 −9 −8 −7 −6 −5

20

40

60

80

100

log10(M)

Re

lative

In

du

ctio

n [

%]




206

−11 −10 −9 −8 −7 −6 −5

20

40

60

80

100

log10(M)

Re

lative

In

du

ctio

n*

[%]


−11 −10 −9 −8 −7 −6 −5

20

40

60

80

100

120

log10(M)R

ela

tive

In

du

ctio

n*

[%]


−11 −10 −9 −8 −7 −6 −50

20

40

60

80

100

log10(M)

Re

lative

In

du

ctio

n*

[%]

TI−CIT2LK, run 15, Citoxlab, int=78.74

−11 −10 −9 −8 −7 −6 −50

20

40

60

80

100

120

140

log10(M)

Re

lative

In

du

ctio

n*

[%]


−11 −10 −9 −8 −7 −6 −50

20

40

60

80

100

120

log10(M)

Re

lative

In

du

ctio

n*

[%]


−11 −10 −9 −8 −7 −6 −50

20

40

60

80

100

log10(M)

Re

lative

In

du

ctio

n*

[%]


−8 −7 −6 −50

20

40

60

80

100

log10(M)

Re

lative

In

du

ctio

n*

[%]

TI−02SH, run 3, RISE, int=84.08

−8 −7 −6 −5

20

40

60

80

100

log10(M)

Re

lative

In

du

ctio

n*

[%]


−8 −7 −6 −5

20

40

60

80

100

log10(M)

Re

lative

In

du

ctio

n*

[%]


−11 −10 −9 −8 −7 −6 −50

20

40

60

80

100

log10(M)

Re

lative

In

du

ctio

n*

[%]


−11 −10 −9 −8 −7 −6 −50

20

40

60

80

100

log10(M)

Re

lative

In

du

ctio

n*

[%]


−11 −10 −9 −8 −7 −6 −5

20

40

60

80

100

log10(M)

Re

lative

In

du

ctio

n*

[%]





207

−11 −10 −9 −8 −7 −6 −50

20

40

60

80

100

log10(M)

Rela

tive Induction [%

]


run 5

run 13

run 15

Flutamide

−11 −10 −9 −8 −7 −6 −50

20

40

60

80

100

120

140

log10(M)

Rela

tive Induction [%

]

TI−ENV2ZR, Envigo

run 1

run 2

run 4

Flutamide

−8 −7 −6 −50

20

40

60

80

100

120

140

160

180

200

220

240

log10(M)

Rela

tive Induction [%

]

TI−02SH, RISE

run 3

run 8

run 11

Flutamide

−11 −10 −9 −8 −7 −6 −50

20

40

60

80

100

log10(M)

Rela

tive Induction [%

]

TI−BDS2YN, BDS

run 2

run 3

run 4

Flutamide


208

Citoxlab

Envigo

RISE

BDS

run5

run13

run15

run1

run2

run4

run3

run8

run11

run2

run3

run4

[µM]

[mg/ml]

PRE

PRE

PRE

PRE

PRE

PRE

COM

COM

COM

PRE

PRE

PRE

2.32e-6

5e-10

100.3(9.4)

85.2(29.5)

87.8

(5.5)

6.95e-6

1.5e-9

104(8.5)102.1(9)

111(7.5)

98.5(5.3)89.8(5.2)105.7(2)

2.32e-5

5e-9

95.8(11.3)

99.4(13.5)

101.7(5.3)

6.95e-5

1.5e-8

118.3(5.2)116.8(13.3)103.8(16.3)

92.9(5.1)97.4(4.5)105.5(4.8)

2.32e-4

5e-8

100.3(6.6)

97.7(3.6)

86.7

(4.5)

6.95e-4

1.5e-7

125.9(18.1)115.4(3.8)110.9(6.5)

96.2(3.4)96.3(0.9)103.4(5)

2.32e-3

5e-7

95.8(5.8)

87.4(22.5)

86.8

(5)

6.95e-3

1.5e-6

123(17.6)

111.6(8.7)

87.1(11.2)

94.5(3.5)94.9(2.1)103.9(1.4)

2.09e-2

4.5e-6

98.9

(5.4)

101.5(8.5)

98.7(6.7)

2.32e-2

5e-6

101.1(11.5)100.2(6)

85.8

(2.6)

6.95e-2

1.5e-5

129.4(3.2)103.1(4.6)110.6(4.3)

97.3

(4.3)

97.8(8.4)

98.8(3.5)96.6(1.7)90.2(2.9)106.3(9.7)

2.09e-1

4.5e-5

94.9

(4.6)

94.1(9.7)103.1(8.5)

2.32e-1

5e-5

95.4(3.8)

91.6(25.7)

80.9

(7.7)

6.95e-1

1.5e-4

144.1(16)

103.3(6.2)103.5(7.3)

91.4

(5.5)

93.8(11.4)

100.6(5.3)

90.2(1.4)

91(4.3)100.1(4.6)

2.09

4.5e-4

95.8

(1.3)

95.5(11.5)

97.9(5)

2.32

5e-4

102.7(1.8)

88.3(29)

80.8

(8.8)

6.95

1.5e-3

143.1(6.5)106.5(6.3)103.6(7.3)

93.4

(2.5)

104.8(7.3)101.4(7.4)

94.1(3)

91.4(1.7)101.9(4.8)

20.86

4.5e-3

88.8

(4.1)

91.7(10.5)

101(12)

23.18

5e-3

98.7(8.5)

97(6.6)

77.9

(9.6)

69.54

1.5e-2

110.4(17)

97.9(5.2)

87.6(3.4)

77.6(2.1)

83.4(5.2)

82.1(4)

83(7.4)92.7(2.8)98.9(5.6)

interpvalue(x,y)

(2.5e-3,78.7)

(7.5e-3,84.1)

R2

0.37

0.53

0.32

log 1

0(PC80)[mg/ml]

-2.65

-1.9

log 1

0(IC50)[mg/ml]

-5.75

na


209

Citoxlab

Envigo

RISE

BDS

[mg/ml]run5

run13

run15

run1

run2

run4

run3

run8

run11

run2

run3

run4

5e-10

1.5e-9

5e-9

1.5e-8

5e-8

1.5e-7

5e-7

1.5e-6

4.5e-6

244(4.5)210.3(14.4)235.4(10.8)

5e-6

1.5e-5

238.4(9.5)220.7(6.4)228.6(1.8)

4.5e-5

224.6(12.5)202.9(20.6)

236(10.1)

5e-5

1.5e-4

224.6(9.3)206.8(19.3)234.8(6.3)

4.5e-4

231.2(10.4)

206(10.7)

234.9(4.1)

5e-4

1.5e-3

242.2(14)

214.2(15.1)236.6(14)

4.5e-3

231.9(19.7)208.3(14.6)248.5(9.1)

5e-3

1.5e-2

223.3(10.1)198.5(7.7)227.3(10.2)



210

−11 −10 −9 −8 −7 −6 −50

20

40

60

80

100

120

140

160

180

200

220

240

log10(M)

Rela

tive Induction [%

]


Citoxlab

Envigo

RISE

BDS

Flutamide


211

D.10 Test item 10

−9 −8 −7 −6 −50

20

40

60

80

100

120

140

160

180

200

220

240

260

280

300

log10(M)

Rela

tive Induction [%

]TI−CIT2GQ, run 8, Citoxlab

−9 −8 −7 −6 −50

20

40

60

80

100

120

140

160

180

200

220

240

260

log10(M)

Rela

tive Induction [%

]


−9 −8 −7 −6 −50

20

40

60

80

100

120

140

160

180

200

220

240

260

log10(M)

Rela

tive Induction [%

]


−9 −8 −7 −6 −5

20

40

60

80

100

120

140

160

180

200

220

log10(M)

Rela

tive Induction [%

]


−9 −8 −7 −6 −50

20

40

60

80

100

120

140

160

180

200

220

240

log10(M)

Rela

tive Induction [%

]TI−ENV2GK, run 6, Envigo

−9 −8 −7 −6 −50

20

40

60

80

100

120

140

160

180

200

220

log10(M)

Rela

tive Induction [%

]


−9 −8 −7 −6 −50

20

40

60

80

100

120

140

160

180

200

220

log10(M)

Rela

tive Induction [%

]


−9 −8 −7 −6 −5

20

40

60

80

100

120

140

160

180

200

log10(M)

Rela

tive Induction [%

]


−9 −8 −7 −6 −5

20

40

60

80

100

120

140

160

180

200

220

240

log10(M)

Rela

tive Induction [%

]


−8 −7 −6 −50

20

40

60

80

100

120

140

160

180

200

220

240

260

log10(M)

Re

lative

In

du

ctio

n [

%]


−9 −8 −7 −6 −50

20

40

60

80

100

120

140

160

180

200

220

240

log10(M)

Rela

tive Induction [%

]


−9 −8 −7 −6 −5

20

40

60

80

100

120

140

160

180

200

220

log10(M)

Rela

tive Induction [%

]


Figure 183: Test item 10. Relative induction responses for accepted experiments in three partici-parting labs. Legend: relative Induction Yc ( ), Specificity control Sc ( ), single replicate for Yc( ), single replicate for Y S


212

−9 −8 −7 −6 −50

20

40

60

80

100

log10(M)

Rela

tive Induction*

[%]


−9 −8 −7 −6 −50

20

40

60

80

100

120

140

160

180

log10(M)R

ela

tive Induction*

[%]


−9 −8 −7 −6 −50

20

40

60

80

100

log10(M)

Rela

tive Induction*

[%]


−9 −8 −7 −6 −5

20

40

60

80

100

120

log10(M)

Rela

tive Induction*

[%]


−9 −8 −7 −6 −50

20

40

60

80

100

log10(M)

Rela

tive Induction*

[%]


−9 −8 −7 −6 −50

20

40

60

80

100

120

log10(M)

Rela

tive Induction*

[%]


−9 −8 −7 −6 −50

20

40

60

80

100

log10(M)

Rela

tive Induction*

[%]


−9 −8 −7 −6 −5

20

40

60

80

100

log10(M)

Rela

tive Induction*

[%]


−9 −8 −7 −6 −5

20

40

60

80

100

120

log10(M)

Rela

tive Induction*

[%]TI−04LR, run 11, RISE

−8 −7 −6 −5

0

20

40

60

80

100

log10(M)

Re

lative

In

du

ctio

n*

[%]


−9 −8 −7 −6 −50

20

40

60

80

100

log10(M)

Rela

tive Induction*

[%]


−9 −8 −7 −6 −5

20

40

60

80

100

log10(M)

Rela

tive Induction*

[%]





213

−9 −8 −7 −6 −50

20

40

60

80

100

120

140

160

180

200

220

240

260

280

log10(M)

Rela

tive Induction [%

]

TI−CIT2GQ, Citoxlab

run 8

run 18

run 20

Flutamide

−9 −8 −7 −6 −50

20

40

60

80

100

120

140

160

180

200

220

log10(M)

Rela

tive Induction [%

]

TI−ENV2GK, Envigo

run 5

run 6

run 7

Flutamide

−9 −8 −7 −6 −50

20

40

60

80

100

120

140

160

180

200

220

log10(M)

Rela

tive Induction [%

]

TI−04LR, RISE

run 3

run 8

run 11

Flutamide

−9 −8 −7 −6 −50

20

40

60

80

100

120

140

160

180

200

220

240

log10(M)

Rela

tive Induction [%

]

TI−BDS2SD, BDS

run 11

run 14

run 17

Flutamide

Figure 185: Test item 10. Relative induction responses for accepted experiments in three partici-parting labs. Aggregated by laboratory.

214

Citoxlab

Envigo

RISE

BDS

run8

run18

run20

run5

run6

run7

run3

run8

run11

run11

run14

run17

[µM]

[mg/ml]

COM

COM

COM

COM

COM

COM

COM

COM

COM

COM

COM

COM

4.55e-4

1.35e-7

87.8(1.1)95.7(7.9)

49(1.5)109.9(10.9)101.4(2.1)

99(9.1)

104.8(12.2)99.2(1.9)95.3(4.9)

5.06e-4

1.5e-7

92.3(13)

95.8(7.2)

1.52e-3

4.5e-7

82.8(6.5)93.5(4.7)93.8(0.8)

86.4(4.1)

85.5(20)

100.1(16.2)

95.4(2.9)

88.1(5.8)100.5(7.7)

1.69e-3

5e-7

84.5(9)

92.7(5.7)

4.55e-3

1.35e-6

78.9(3.4)95.6(8)

88.9(2.6)

83.9(3.2)

89.3(16)

93.5(6.5)

85.1

(5)

83.1(7.4)88.2(2.5)

5.06e-3

1.5e-6

88.4(4.9)85.8(4.3)

1.52e-2

4.5e-6

64.9(2.6)

69(5)

67.5(1.6)

67.7(4.5)

70.5(4.1)83.3(14)

71.4(3)

73.2(3.2)

66.7(3.4)

58.8(3.2)

1.69e-2

5e-6

72.9(3.7)

74.5(5.2)

4.55e-2

1.35e-5

48.4(3.6)

44.5(4.5)

42.6(3.5)

40.9(6.6)

43.8(7.1)

54.9(9.7)

46.7(2.1)

47.2(6)

45.3(0.7)

5.06e-2

1.5e-5

28.3(0.5)

39.5(5.4)

46.7(6.1)

1.52e-1

4.5e-5

17.7(1.2)

15.4(1.1)

18.5(0.5)

18.1(1.5)

21.7(0.3)

24(6.9)

19.3(1)

22.9(2)

18.4(1.7)

11.7(0.4)

1.69e-1

5e-5

18.6(2.5)

21.8(0.8)

4.55e-1

1.35e-4

7.4(2)

5.8(0.1)

5.9(0)

4.6(1.3)

9.4(0.6)

7.3(2.1)

7.8(0.2)

9.1(0.6)

7(0.5)

5.06e-1

1.5e-4

5.1(0.3)

7.5(1.3)

7.5(0.3)

1.52

4.5e-4

32.4(0.8)

2.6(0.3)

3.1(0.4)

3.3(0.5)

3.1(0.9)

2.2(0.3)

3.5(0.3)

4.2(0.7)

3.5(0.7)

6.8(0.5)

1.69

5e-4

3.8(1)

3.6(0.2)

5.06

1.5e-3

9.3(0.9)

15.18

4.5e-3

5.5(0.6)

50.61

1.5e-2

-0.4(1.5)

R2

0.04

0.54

0.51

0.27

0.31

0.26

0.75

0.46

0.26

0.38

0.58

0.59

log 1

0(PC80)[mg/ml]

-5.94

-5.53

-5.62

-5.67

-5.54

-5.27

-5.63

-5.6

-5.66

-5.44

-5.47

log 1

0(IC50)[mg/ml]

-5.02

-4.97

-4.81

-5.1

-4.94

-4.79

-4.98

-4.87

-5-5.08

-4.91

-4.83


215

Citoxlab

Envigo

RISE

BDS

[mg/ml]

run8

run18

run20

run5

run6

run7

run3

run8

run11

run11

run14

run17

1.35e-7

267.9(4.7)

235(8.5)

256.4(3.4)

211(4.7)

220(4.7)

175(25.6)

229.2(9)

197.4(16.7)

210(3.6)

1.5e-7

213(18)

225.8(14.6)

4.5e-7

257(8.7)

232.3(4.5)

251.6(14.4)

190.3(20)

216.3(25.5)180.8(21.3)228.6(9)

200.1(14.2)

213(8.1)

5e-7

225.4(14.2)

209(7.3)

1.35e-6

269.3(14.7)

240.6(18.2)

261.6(12.9)

165.4(25.5)226.6(21)

194.8(16.8)

217(7.1)

194.3(20.1)

229.6(8.1)

1.5e-6

214(23.8)

216.2(3.3)

4.5e-6

276.6(13.1)

234.7(18.2)

257.5(12.5)

210.4(14.6)

187.5(9.4)201.4(33.3)217.5(5.7)

187.2(3.3)

228.3(6.9)

249.2(9.3)

5e-6

201.1(14.1)220.4(3)

1.35e-5

294.1(16.3)

237.2(23.1)

243.1(8.6)

192.3(5.1)227.4(11.3)

185(21.7)

215.3(19)

190.2(4.3)

238.3(16.7)

1.5e-5

255.6(9.5)197.6(38.8)211.1(8.5)

4.5e-5

273.8(8.7)

227.8(27)

250.5(7.2)

197.4(28.3)

220.5(18.1)192.2(10.5)210.5(3.1)

190.3(11.5)

217.7(4.7)

235.1(7.7)

5e-5

209.2(22)

210.4(3.3)

1.35e-4

259.5(7.7)

207.9(11.2)

227.3(7.9)

174.2(5.8)194.3(15.7)176.7(13.5)201.9(10.9)

188.3(4.4)

201.2(6.9)

1.5e-4

204.7(12.3)

193.9(15.2)201.9(6.9)

4.5e-4

204.8(5.4)

174.9(11.5)

184.9(10.2)

146.4(8.5)

156(19.4)

145.8(17.9)

179.6(3)

149.9(4.8)

161.6(8.6)

157.9(5.4)

5e-4

174.7(3.6)

179.7(2.7)

1.5e-3

60.3(0.4)

4.5e-3

14.3(1.3)

1.5e-2

5.8

(1)



216

−9 −8 −7 −6 −50

20

40

60

80

100

120

140

160

180

200

220

240

260

280

log10(M)

Rela

tive Induction [%

]


Citoxlab

Envigo

RISE

BDS

Flutamide

Figure 186: Test item 10. Relative induction responses for accepted experiments in three partici-parting labs. Aggregated by laboratory and biological replicate.

217

D.11 Test item 11

−11 −10 −9 −8 −7 −6 −5

20

40

60

80

100

log10(M)

Re

lative

In

du

ctio

n [

%]


−11 −10 −9 −8 −7 −6 −50

20

40

60

80

log10(M)

Rela

tive Induction [%

]


−11 −10 −9 −8 −7 −6 −5

20

40

60

80

100

120

140

log10(M)

Re

lative

In

du

ctio

n [

%]


−10 −9 −8 −7 −6 −5 −4

20

40

60

80

100

120

log10(M)

Re

lative

In

du

ctio

n [

%]


−10 −9 −8 −7 −6 −5 −40

20

40

60

80

100

120

log10(M)

Re

lative

In

du

ctio

n [

%]


−10 −9 −8 −7 −6 −5 −4

20

40

60

80

100

120

log10(M)

Re

lative

In

du

ctio

n [

%]


−10 −9 −8 −7 −6 −5 −4

20

40

60

80

100

120

log10(M)

Re

lative

In

du

ctio

n [

%]


−10 −9 −8 −7 −6 −5 −40

20

40

60

80

100

120

log10(M)

Re

lative

In

du

ctio

n [

%]


−10 −9 −8 −7 −6 −5 −4

20

40

60

80

100

120

log10(M)

Re

lative

In

du

ctio

n [

%]


−10 −9 −8 −7 −6 −5 −4

20

40

60

80

100

log10(M)

Re

lative

In

du

ctio

n [

%]


−10 −9 −8 −7 −6 −5 −40

20

40

60

80

100

log10(M)

Re

lative

In

du

ctio

n [

%]


−10 −9 −8 −7 −6 −5 −4

20

40

60

80

100

log10(M)

Re

lative

In

du

ctio

n [

%]




218

−11 −10 −9 −8 −7 −6 −50

20

40

60

80

100

120

log10(M)

Rela

tive Induction [%

]

TI−CIT2ZT, Citoxlab

run 3

run 12

run 14

Flutamide

−10 −9 −8 −7 −6 −5 −40

20

40

60

80

100

120

log10(M)

Rela

tive Induction [%

]

TI−ENV3AT, Envigo

run 1

run 2

run 3

Flutamide

−10 −9 −8 −7 −6 −5 −40

20

40

60

80

100

120

log10(M)

Rela

tive Induction [%

]

TI−11AM, RISE

run 1

run 15

run 29

Flutamide

−10 −9 −8 −7 −6 −5 −40

20

40

60

80

100

log10(M)

Rela

tive Induction [%

]

TI−BDS2XH, BDS

run 1

run 3

run 4

Flutamide


219

Citoxlab

Envigo

RISE

BDS

run3

run12

run14

run1

run2

run3

run1

run15

run29

run1

run3

run4

[µM]

[mg/ml]

PRE

PRE

PRE

PRE

PRE

PRE

PRE

PRE

PRE

PRE

PRE

PRE

7.69e-6

5e-10

89.5(7.4)

93(4.4)129.6(9.4)

2.31e-5

1.5e-9

96.3(5.4)106.9(7.3)

95(5.9)107.5(4.3)

93.5(3.1)106.6(8.5)

107.2(12.5)98.7(6.8)93.2(6.1)

7.69e-5

5e-9

94.3(3.7)

93(4.4)89.3(23.3)

2.31e-4

1.5e-8

93.2(14.5)

103.2(7.9)100.5(3)

106.7(5.8)

102.5(5.5)108.2(1.4)

104.7(10.7)100.6(1.1)

96.8(2.1)

7.69e-4

5e-8

113.1(4.6)86.9(6.6)135.2(21.2)

2.31e-3

1.5e-7

96.9(11)

106.3(6.8)104.3(5.9)

108.9(7.6)

106.3(19.4)113.5(8.2)

107.1(5.1)

94.5(4.2)98.6(6)

7.69e-3

5e-7

103.6(8.1)88.8(8)

117.6(17.1)

2.31e-2

1.5e-6

97.6

(9)

112.8(4.6)127.2(2.6)

105.9(3.1)

94.4(0.9)

112(9.3)101.5(5)

95.5(2)

100.5(4.9)

7.69e-2

5e-6

98.6(7.2)83.2(1.7)106.7(34)

2.31e-1

1.5e-5

96.8(4.2)

121(6.1)

97.6(5.5)

96.7(2.3)90.3(16.5)

109.8(4.2)

104.7(7.9)

96.4(5.9)98.9(4.9)

7.69e-1

5e-5

94.9(6.5)90.4(4.4)

102(30.4)

2.31

1.5e-4

87.9(11.4)

107.1(5.2)100.8(4.7)

102.3(1.2)

90.2(3.3)113.5(4.5)

107.5(10.8)93.4(4.7)101.4(6)

7.69

5e-4

95.8(10.4)

87.1(8.1)121.4(6.2)

23.08

1.5e-3

93.3(10.6)

109.6(23.2)

99(4.1)104.2(3.8)

92.1(5.8)109.5(5.1)

102.5(10.2)96.9(4.9)96.1(3.3)

76.92

5e-3

96.9

(8)

87.7(5.2)109.7(23.5)

230.77

1.5e-2

129.1(5)

123.6(4.5)113.6(4.8)

121.9(1.8)

109.9(4.1)115.5(7.1)

112(9.2)104.1(6.6)

99.6(5.5)

R2

log 1

0(PC80)[mg/ml]

log 1

0(IC50)[mg/ml]


220

−11 −10 −9 −8 −7 −6 −5 −40

20

40

60

80

100

120

log10(M)

Rela

tive Induction [%

]


Citoxlab

Envigo

RISE

BDS

Flutamide


221

D.12 Test item 12

−10 −9 −8 −7 −6 −5 −4

0

20

40

60

80

100

log10(M)

Re

lative

In

du

ctio

n [

%]


−10 −9 −8 −7 −6 −5 −40

20

40

60

80

100

120

140

160

log10(M)

Re

lative

In

du

ctio

n [

%]


−10 −9 −8 −7 −6 −5 −4

20

40

60

80

100

120

log10(M)

Re

lative

In

du

ctio

n [

%]


−11 −10 −9 −8 −7 −6 −5

20

40

60

80

100

log10(M)

Re

lative

In

du

ctio

n [

%]


−11 −10 −9 −8 −7 −6 −50

20

40

60

80

100

log10(M)

Re

lative

In

du

ctio

n [

%]


−11 −10 −9 −8 −7 −6 −5

20

40

60

80

100

log10(M)

Re

lative

In

du

ctio

n [

%]


−11 −10 −9 −8 −7 −6 −50

20

40

60

80

log10(M)

Rela

tive Induction [%

]


−11 −10 −9 −8 −7 −6 −50

20

40

60

80

100

120

log10(M)

Re

lative

In

du

ctio

n [

%]


−11 −10 −9 −8 −7 −6 −5

20

40

60

80

100

log10(M)

Re

lative

In

du

ctio

n [

%]


−10 −9 −8 −7 −6 −5 −40

20

40

60

80

100

log10(M)

Re

lative

In

du

ctio

n [

%]


−10 −9 −8 −7 −6 −5 −40

20

40

60

80

100

log10(M)

Re

lative

In

du

ctio

n [

%]


−10 −9 −8 −7 −6 −5 −4

20

40

60

80

100

log10(M)

Re

lative

In

du

ctio

n [

%]




222

−10 −9 −8 −7 −6 −5 −4

0

20

40

60

80

100

120

140

160

log10(M)

Rela

tive Induction [%

]

TI−CIT2DQ, Citoxlab

run 2

run 12

run 14

Flutamide

−11 −10 −9 −8 −7 −6 −50

20

40

60

80

100

log10(M)

Rela

tive Induction [%

]

TI−ENV3FJ, Envigo

run 1

run 2

run 3

Flutamide

−11 −10 −9 −8 −7 −6 −50

20

40

60

80

100

log10(M)

Rela

tive Induction [%

]

TI−18SJ, RISE

run 7

run 15

run 29

Flutamide

−10 −9 −8 −7 −6 −5 −40

20

40

60

80

log10(M)

Rela

tive Induction [%

]

TI−BDS2BU, BDS

run 2

run 3

run 4

Flutamide


223

Citoxlab

Envigo

RISE

BDS

run2

run12

run14

run1

run2

run3

run7

run15

run29

run2

run3

run4

[µM]

[mg/ml]

PRE

PRE

PRE

PRE

PRE

PRE

PRE

PRE

PRE

PRE

PRE

PRE

3.84e-6

1.5e-9

96.7(9.8)

90.8(9.7)104.9(1.1)

89.6

(6.2)

108.9(20.9)101.4(3.6)

1.28e-5

5e-9

98.9(10.7)

92.5(5)

106.5(6.2)

94.5(1.4)98.3(3.7)96.4(7.1)

3.84e-5

1.5e-8

92.4(18.7)

105.8(3.9)

105.7(6)

85(3)

102.9(2.1)107.3(6.7)

1.28e-4

5e-8

91(1.6)

94.6(5.2)106.7(4.9)

94.1(2.7)

97(2.9)98.7(3.8)

3.84e-4

1.5e-7

98.4(6.8)

98.1(6.8)106.1(2.4)

83.3

(9.1)

101.9(5.6)

108(2.9)

1.28e-3

5e-7

91.5(3.2)

96(2.9)107.4(5.5)

90.7(3.7)

98(2.9)93.1(6.1)

3.84e-3

1.5e-6

93.5(1.2)102.5(5.6)

113.2(3.1)

79.3(11.2)

101.6(6)

101.7(2.8)

1.28e-2

5e-6

96(4.9)

95.4(3.3)

112(4.5)

93.8(6.5)94.2(3.6)85.4(8.7)

3.84e-2

1.5e-5

97.7(18.4)

103.2(6.3)

100.8(4.3)

87.4

(3.7)

99.9(9.9)104.3(9.6)

1.28e-1

5e-5

98.2(3)

93.2(3.4)113.8(9.6)

94(2.8)94.4(4.5)92.2(12)

3.84e-1

1.5e-4

98.7(12.8)

95.4(6.6)110.7(3.4)

80.4

(3.8)

97.4(4.6)105.8(6.3)

1.28

5e-4

97.7(2.1)

96(1.9)114.1(5.3)

94(6.7)

97(1.6)91.3(7.4)

3.84

1.5e-3

85.4(10.3)

92.9(3.1)102.7(2.5)

80.6

(5.1)

96(11.3)

104.5(5.8)

12.8

5e-3

87.5(4.1)

82.5(0.3)105.2(18.7)

88.1(3.3)94.7(3.1)89.6(6.7)

38.4

1.5e-2

86.1(12.1)

93.6(4.1)103.8(8.6)

76.1

(5.1)

101.4(4.3)

85.7(3.4)

128.01

5e-2

85(4.4)163.8(4.9)

101.6(7.9)

81.6(0.7)81.7(2.3)87.4(5.3)

interpvalue(x,y)

(7.5e-3,77.4)

R2

log 1

0(PC80)[mg/ml]

nalog 1

0(IC50)[mg/ml]

na


224

−11 −10 −9 −8 −7 −6 −5 −4

0

20

40

60

80

100

120

140

160

log10(M)

Rela

tive Induction [%

]


Citoxlab

Envigo

RISE

BDS

Flutamide


225

D.13 Test item 13

−11 −10 −9 −8 −7 −6 −5

20

40

60

80

100

120

140

160

180

200

220

240

260

280

300

320

340

log10(M)

Re

lative

In

du

ctio

n [

%]


−11 −10 −9 −8 −7 −6 −50

20

40

60

80

100

120

140

160

180

200

220

log10(M)

Re

lative

In

du

ctio

n [

%]


−11 −10 −9 −8 −7 −6 −5

20

40

60

80

100

120

140

160

180

200

220

240

log10(M)

Re

lative

In

du

ctio

n [

%]


−11 −10 −9 −8 −7 −6 −50

20

40

60

80

100

120

140

160

180

200

220

log10(M)

Re

lative

In

du

ctio

n [

%]


−11 −10 −9 −8 −7 −6 −5

20

40

60

80

100

120

140

160

180

200

220

log10(M)

Re

lative

In

du

ctio

n [

%]


−11 −10 −9 −8 −7 −6 −5

20

40

60

80

100

120

140

160

180

200

log10(M)

Re

lative

In

du

ctio

n [

%]


−11 −10 −9 −8 −7 −6 −50

20

40

60

80

100

120

140

160

180

200

220

240

260

log10(M)

Re

lative

In

du

ctio

n [

%]


−11 −10 −9 −8 −7 −6 −50

20

40

60

80

100

120

140

160

180

200

log10(M)

Re

lative

In

du

ctio

n [

%]


−11 −10 −9 −8 −7 −6 −5

20

40

60

80

100

120

140

160

180

200

log10(M)

Re

lative

In

du

ctio

n [

%]


−11 −10 −9 −8 −7 −6 −50

20

40

60

80

100

120

140

160

180

200

220

log10(M)

Re

lative

In

du

ctio

n [

%]


−11 −10 −9 −8 −7 −6 −50

20

40

60

80

100

120

140

160

180

200

log10(M)

Re

lative

In

du

ctio

n [

%]


−11 −10 −9 −8 −7 −6 −5

20

40

60

80

100

120

140

160

180

200

220

240

260

280

log10(M)

Re

lative

In

du

ctio

n [

%]




226

−11 −10 −9 −8 −7 −6 −50

20

40

60

80

100

120

140

160

180

200

220

240

260

280

300

320

log10(M)

Re

lative

In

du

ctio

n [

%]

TI−CIT2TJ, Citoxlab

run 3

run 12

run 13

Flutamide

−11 −10 −9 −8 −7 −6 −50

20

40

60

80

100

120

140

160

180

200

220

log10(M)

Re

lative

In

du

ctio

n [

%]

TI−ENV3UJ, Envigo

run 2

run 3

run 8

Flutamide

−11 −10 −9 −8 −7 −6 −50

20

40

60

80

100

120

140

160

180

200

220

240

log10(M)

Re

lative

In

du

ctio

n [

%]

TI−09NY, RISE

run 15

run 21

run 26

Flutamide

−11 −10 −9 −8 −7 −6 −50

20

40

60

80

100

120

140

160

180

200

220

240

260

log10(M)

Re

lative

In

du

ctio

n [

%]

TI−BDS2VF, BDS

run 2

run 3

run 4

Flutamide


227

Citoxlab

Envigo

RISE

BDS

run3

run12

run13

run2

run3

run8

run15

run21

run26

run2

run3

run4

[µM]

[mg/ml]

PRE

PRE

PRE

PRE

PRE

PRE

PRE

PRE

PRE

PRE

PRE

PRE

1.64e-6

5e-10

107.9(3.9)

87.7(4.7)

95.8(5.7)

106.9(2.5)106.3(6.1)

94(2)

109.8(11.7)100.2(2.4)

94.7(5.2)

96.2(8.5)

98.4(9.4)

97.1(8.6)

1.64e-5

5e-9

123.6(4.2)

84.7(8.5)

93.5(5.5)

113.1(1.1)115.1(2)

95(10)

111.5(2.6)

99.5(3.7)104.1(1.2)

100.8(2.7)

99.5(11)

101.1(6.9)

1.64e-4

5e-8

182.6(16.1)117.2(10)

130.5(20.2)147.4(9.1)

125(8.8)127.5(12)

150.6(11.1)121.4(3.1)133.9(2.3)

138.5(4.5)128.9(13.3)143.7(15.9)

1.64e-3

5e-7

303.4(7.5)193.8(8.5)205.9(14.9)180.1(14.4)189.3(18.3)

185(10.7)

216.6(8)

185.7(15.6)190.2(1.3)

204.7(12.9)176.7(9.4)232.9(15.6)

1.64e-2

5e-6

333.2(6)

211.5(20.4)207.4(7.8)

211.8(15.3)202.2(13)

207.7(7)

229.2(22.6)197.6(2.7)

202(2.4)

224.7(9.9)197.4(22.3)262.6(20.7)

1.64e-1

5e-5

330.7(3.5)215.5(5.8)214.8(9.5)

226.5(10.3)208.7(22.5)197.5(7.8)

242.1(24.2)202.7(6.1)204.3(11.7)

221(15.3)

194.9(18.5)

263(19.8)

1.64

5e-4

333.4(17.5)211.3(13)

211.8(27.3)206.4(7)

197.1(22.4)209.2(9)

222.7(2.7)200.1(6.2)190.9(6)

224(13.3)

199(20.6)

248.7(16.3)

16.42

5e-3

248.3(9.4)158.9(7.2)159.2(9.4)

151.6(11.5)151.6(12.5)172.6(7.3)

176.7(9.3)152.2(6.1)147.1(7.4)

178.1(11.1)157.7(6)

216.1(9.2)

R2

log 1

0(PC80)[mg/ml]

log 1

0(IC50)[mg/ml]


228

−11 −10 −9 −8 −7 −6 −50

20

40

60

80

100

120

140

160

180

200

220

240

260

280

300

320

log10(M)

Rela

tive Induction [%

]


Citoxlab

Envigo

RISE

BDS

Flutamide


229

D.14 Test item 14

−8 −7 −6 −5

20

40

60

80

100

120

140

160

180

200

220

240

260

280

300

log10(M)

Re

lative

In

du

ctio

n [

%]


−8 −7 −6 −50

20

40

60

80

100

120

140

160

180

200

220

240

260

log10(M)

Re

lative

In

du

ctio

n [

%]


−8 −7 −6 −50

20

40

60

80

100

120

140

160

180

200

220

240

log10(M)

Re

lative

In

du

ctio

n [

%]


−8 −7 −6 −50

20

40

60

80

100

120

140

160

180

200

220

240

log10(M)

Re

lative

In

du

ctio

n [

%]


−8 −7 −6 −50

20

40

60

80

100

120

140

160

180

200

log10(M)

Re

lative

In

du

ctio

n [

%]


−8 −7 −6 −50

20

40

60

80

100

120

140

160

180

200

220

240

260

log10(M)

Re

lative

In

du

ctio

n [

%]


−8 −7 −6 −5

20

40

60

80

100

120

140

160

180

200

220

240

log10(M)

Re

lative

In

du

ctio

n [

%]


−8 −7 −6 −5

20

40

60

80

100

120

140

160

180

200

220

log10(M)

Rela

tive Induction [%

]


−8 −7 −6 −50

20

40

60

80

100

120

140

160

180

200

220

240

260

280

300

320

log10(M)

Rela

tive Induction [%

]


−8 −7 −6 −50

20

40

60

80

100

120

140

160

180

200

220

240

260

log10(M)

Re

lative

In

du

ctio

n [

%]


−8 −7 −6 −50

20

40

60

80

100

120

140

160

180

200

220

240

260

log10(M)

Re

lative

In

du

ctio

n [

%]


−8 −7 −6 −50

20

40

60

80

100

120

140

160

180

200

220

240

260

log10(M)

Re

lative

In

du

ctio

n [

%]




230

−8 −7 −6 −5

20

40

60

80

100

log10(M)

Re

lative

In

du

ctio

n*

[%]


−8 −7 −6 −50

20

40

60

80

100

log10(M)R

ela

tive

In

du

ctio

n*

[%]


−8 −7 −6 −50

20

40

60

80

100

log10(M)

Re

lative

In

du

ctio

n*

[%]


−8 −7 −6 −50

20

40

60

80

100

120

log10(M)

Re

lative

In

du

ctio

n*

[%]


−8 −7 −6 −50

20

40

60

80

100

log10(M)

Re

lative

In

du

ctio

n*

[%]


−8 −7 −6 −50

20

40

60

80

100

120

140

160

180

200

log10(M)

Re

lative

In

du

ctio

n*

[%]


−8 −7 −6 −5

20

40

60

80

100

log10(M)

Re

lative

In

du

ctio

n*

[%]


−8 −7 −6 −5

20

40

60

80

100

log10(M)

Rela

tive Induction*

[%]


−8 −7 −6 −50

20

40

60

80

100

log10(M)

Rela

tive Induction*

[%]TI−22RU, run 34, RISE

−8 −7 −6 −50

20

40

60

80

100

log10(M)

Re

lative

In

du

ctio

n*

[%]


−8 −7 −6 −50

20

40

60

80

100

log10(M)

Re

lative

In

du

ctio

n*

[%]


−8 −7 −6 −50

20

40

60

80

100

120

140

log10(M)

Re

lative

In

du

ctio

n*

[%]





231

−8 −7 −6 −50

20

40

60

80

100

120

140

160

180

200

220

240

260

280

300

log10(M)

Rela

tive Induction [%

]

TI−CIT2NN, Citoxlab

run 9

run 19

run 21

Flutamide

−8 −7 −6 −50

20

40

60

80

100

120

140

160

180

200

220

240

260

log10(M)

Rela

tive Induction [%

]

TI−ENV3GU, Envigo

run 5

run 6

run 7

Flutamide

−8 −7 −6 −50

20

40

60

80

100

120

140

160

180

200

220

240

260

280

300

320

log10(M)

Rela

tive Induction [%

]

TI−22RU, RISE

run 13

run 22

run 34

Flutamide

−8 −7 −6 −50

20

40

60

80

100

120

140

160

180

200

220

240

260

log10(M)

Rela

tive Induction [%

]

TI−BDS2AJ, BDS

run 5

run 9

run 15

Flutamide


232

Citoxlab

Envigo

RISE

BDS

run9

run19

run21

run5

run6

run7

run13

run22

run34

run5

run9

run15

[µM]

[mg/ml]

COM

COM

COM

COM

COM

COM

COM

COM

COM

COM

COM

COM

1.57e-3

4.5e-7

91.9(2.6)93.3(3.2)

4.72e-3

1.35e-6

103.5(3.1)

88.4(3.3)

88(4.8)85.3(6.8)

96.3(9.1)144.7(60.8)

91.1(4.1)92.1(4.1)102.5(8)

5.24e-3

1.5e-6

88.9(3.6)86.9(9.4)91.8(5.5)

1.57e-2

4.5e-6

91.2(1.8)

87(7.3)

78(0.2)

77.8(7.9)

86.2(8.7)

89.8

(9)

91.1(5.3)82.2(1.8)82.3(4.6)80.9(7.1)80.7(0.3)

1.75e-2

5e-6

82.9(2.1)

4.72e-2

1.35e-5

69(3.9)

63.6(5.4)

63.6(3.8)

62.6(18.1)

71.4(15.4)

118.8(71.9)

59.3(2)

67.7(4.5)

49.5(8.1)

5.24e-2

1.5e-5

63.8(9.1)

65.2(3.7)

63.6(1.6)

1.57e-1

4.5e-5

43.5(3.5)

30.8(3.1)

33.5(2.1)

49.1(5.3)

43.8(4.4)

49.8(2.8)

35.4(1.1)

33.6(0.9)

30.4(0.3)

38.5(3)

23.9(2.1)

1.75e-1

5e-5

34.5(0.5)

4.72e-1

1.35e-4

14.3(0.8)

8(0.5)

9.9(0.8)

22.9(2.4)

18.7(2.1)

16.4(1.3)

10.1(0.9)

12.5(0.6)

13.4(2.6)

5.24e-1

1.5e-4

10.8(2.4)

10.3(1.4)

11.3(1.6)

1.57

4.5e-4

3.7(0.3)

1.6(0.3)

1.8(0.1)

4.1(0.6)

4.4(1.1)

7(0.4)

2.1(0.1)

2.6(1)

2.1(0.4)

2.5(0.3)

2.5(0.8)

1.75

5e-4

1.2(1.2)

4.72

1.35e-3

1.2(0.1)

0.8(0.2)

0.7(0.1)

1.9(0.1)

3.3(0.8)

1(1.1)

0.8(0.2)

0.7(0.2)

1.3(0.6)

5.24

1.5e-3

0.4(0.3)

1(0.6)

1(0.3)

15.73

4.5e-3

1.5(0.4)

1(0.4)

0.9(0.1)

1.2(0.1)

2.3(0.3)

1(0.2)

1.2(0.2)

1.1(0.2)

1.5(0.5)

17.48

5e-3

1.4(1.2)

R2

0.41

0.37

0.33

0.13

0.4

0.45

0.46

0.2

0.57

0.43

0.34

0log 1

0(PC80)[mg/ml]

-5.1

-5.17

-5.45

-5.42

-5.11

-4.54

-5.21

-5.06

-5.26

-5.29

-5.3

-5.34

log 1

0(IC50)[mg/ml]

-4.58

-4.58

-4.54

-4.29

-4.46

-4.42

-4.5

-4.51

-4.56

-4.66

-4.49

-5.05


233

Citoxlab

Envigo

RISE

BDS

[mg/ml]

run9

run19

run21

run5

run6

run7

run13

run22

run34

run5

run9

run15

4.5e-7

213.8(17.5)

321.3(4.4)

1.35e-6

304.8(3.4)

254.9(7)

244.2(12.9)

202.3(18.7)

200.5(8.6)

264.4(12.3)

254.2(6.3)

178.8(45.1)

1.5e-6

229.2(3.7)

212.8(7.5)

312(13.6)

4.5e-6

292.7(7.5)

255.5(6.2)

224.6(6.6)

223(11.3)

204.1(8.2)

214.4(23)

314.8(3.3)

257.4(11.9)

243.7(7.6)

222.3(34.5)

5e-6

237.8(22.8)

1.35e-5

306.2(10.4)

258.7(12.3)

234.6(6.2)

192(67.4)

186.5(8.6)

266.5(19.4)

257.6(2.7)

241.4(18.3)

228.5(35.9)

1.5e-5

238.2(12.9)

213.2(3.1)

306(6.5)

4.5e-5

303.8(16.5)

239.3(3.3)

235.3(9.2)

218.8(10.9)

175.3(41.7)

246.6(14.8)

218.1(6.8)

295.2(12.4)

255.5(3.3)

243.4(4.1)

213.7(53.3)

5e-5

211.7(15.3)

1.35e-4

280.5(6.2)

242.3(13.6)

235.1(10.7)

244.6(1.6)

192.9(3.8)

241.1(23.8)

254.2(15.6)

252.6(16.4)

246.8(15.4)

1.5e-4

224.4(7.7)

225(5.9)

303.1(5.6)

4.5e-4

273.6(6.5)

233.7(12)

216.9(3.5)

200.9(8.5)

191.6(3.4)

245.8(19.7)

201.9(3.7)

273.3(4.9)

215.9(3.4)

233.2(8.6)

235.9(31)

5e-4

206.4(1.7)

1.35e-3

229.4(9.1)

178.3(10.5)

175.6(5.3)

201.4(2.5)

144.2(54.5)240.8(21.8)

194(3.7)

181.4(3.7)

198.2(4.9)

1.5e-3

174.1(23.7)

163.3(6.2)

220.8(1.2)

4.5e-3

140.4(1.8)

95.5(6.7)

100(4.5)

121.1(7.4)

100(8.3)

226.5(10.4)

124.8(2.3)

121.4(7.9)

130.5(10.1)

5e-3

120.3(9.2)

1.35e-2

175.1(18)

4.5e-2

121.5(4.8)



234

−8 −7 −6 −50

20

40

60

80

100

120

140

160

180

200

220

240

260

280

300

320

log10(M)

Rela

tive Induction [%

]


Citoxlab

Envigo

RISE

BDS

Flutamide


235

D.15 Test item 15

−8 −7 −6 −50

20

40

60

80

100

120

140

160

180

200

220

240

260

280

300

320

log10(M)

Re

lative

In

du

ctio

n [

%]


−8 −7 −6 −50

20

40

60

80

100

120

140

160

180

200

220

240

260

log10(M)

Rela

tive Induction [%

]


−8 −7 −6 −5

20

40

60

80

100

120

140

160

180

200

220

240

log10(M)

Rela

tive Induction [%

]


−8 −7 −6 −50

20

40

60

80

100

120

140

160

180

200

220

240

260

280

300

log10(M)

Rela

tive Induction [%

]


−8 −7 −6 −50

20

40

60

80

100

120

140

160

180

200

log10(M)

Rela

tive Induction [%

]TI−ENV3BH, run 6, Envigo

−8 −7 −6 −50

20

40

60

80

100

120

140

160

180

200

220

240

260

log10(M)

Rela

tive Induction [%

]


−8 −7 −6 −50

20

40

60

80

100

120

140

160

180

200

220

240

260

280

log10(M)

Rela

tive Induction [%

]


−8 −7 −6 −5

20

40

60

80

100

120

140

160

180

200

220

240

log10(M)

Rela

tive Induction [%

]


−8 −7 −6 −50

20

40

60

80

100

120

140

160

180

200

220

240

260

280

300

320

340

log10(M)

Rela

tive Induction [%

]


−8 −7 −6 −50

20

40

60

80

100

120

140

160

180

200

220

240

260

280

log10(M)

Re

lative

In

du

ctio

n [

%]


−8 −7 −6 −50

20

40

60

80

100

120

140

160

180

200

220

log10(M)

Re

lative

In

du

ctio

n [

%]


−8 −7 −6 −50

20

40

60

80

100

120

140

160

180

200

220

240

log10(M)

Re

lative

In

du

ctio

n [

%]




236

−8 −7 −6 −50

20

40

60

80

100

log10(M)

Re

lative

In

du

ctio

n*

[%]


−8 −7 −6 −50

20

40

60

80

100

120

140

160

180

log10(M)R

ela

tive Induction*

[%]


−8 −7 −6 −5

20

40

60

80

100

log10(M)

Rela

tive Induction*

[%]


−8 −7 −6 −50

20

40

60

80

100

120

log10(M)

Rela

tive Induction*

[%]


−8 −7 −6 −50

20

40

60

80

100

log10(M)

Rela

tive Induction*

[%]


−8 −7 −6 −50

20

40

60

80

100

log10(M)

Rela

tive Induction*

[%]


−8 −7 −6 −50

20

40

60

80

100

log10(M)

Rela

tive Induction*

[%]


−8 −7 −6 −5

20

40

60

80

100

log10(M)

Rela

tive Induction*

[%]


−8 −7 −6 −50

20

40

60

80

100

log10(M)

Rela

tive Induction*

[%]TI−28ZZ, run 31, RISE

−8 −7 −6 −50

20

40

60

80

100

log10(M)

Re

lative

In

du

ctio

n*

[%]


−8 −7 −6 −50

20

40

60

80

100

log10(M)

Re

lative

In

du

ctio

n*

[%]


−8 −7 −6 −50

20

40

60

80

100

log10(M)

Re

lative

In

du

ctio

n*

[%]





237

−8 −7 −6 −50

20

40

60

80

100

120

140

160

180

200

220

240

260

280

300

320

log10(M)

Rela

tive Induction [%

]

TI−CIT2JB, Citoxlab

run 10

run 18

run 22

Flutamide

−8 −7 −6 −50

20

40

60

80

100

120

140

160

180

200

220

240

260

280

log10(M)

Rela

tive Induction [%

]

TI−ENV3BH, Envigo

run 5

run 6

run 7

Flutamide

−8 −7 −6 −50

20

40

60

80

100

120

140

160

180

200

220

240

260

280

300

320

log10(M)

Rela

tive Induction [%

]

TI−28ZZ, RISE

run 13

run 25

run 31

Flutamide

−8 −7 −6 −50

20

40

60

80

100

120

140

160

180

200

220

240

260

280

log10(M)

Rela

tive Induction [%

]

TI−BDS2AN, BDS

run 6

run 8

run 10

Flutamide


238

Citoxlab

Envigo

RISE

BDS

run10

run18

run22

run5

run6

run7

run13

run25

run31

run6

run8

run10

[µM]

[mg/ml]

COM

COM

COM

COM

COM

COM

COM

COM

COM

COM

COM

COM

3.98e-3

1.5e-6

88.7(2.3)

90.4(11.2)

105.5(7.9)

95.1(2.4)

97.5(1.1)96.5(6)

1.19e-2

4.5e-6

101.9(6.2)

97.7(5.9)

101.9(7.4)

97.1(4.2)98.1(2.5)94.3(6.4)

1.33e-2

5e-6

93.7(2.2)

99.2(3.5)108.7(1.6)

102.6(7.4)

91.4(4.3)99.1(1)

3.98e-2

1.5e-5

96.1(4.1)

93(7.1)

96(5.8)104.6(9.3)105.4(3.4)

96(6.5)104.1(7)

100.3(7.7)

97.8(3.9)

98(4.9)96.4(3.6)96.8(4.7)

1.19e-1

4.5e-5

98.9(7.2)90.5(4.2)

98.2(15.8)

97.1(1.6)88.2(1.9)90.3(2)

1.33e-1

5e-5

96(3)

105.8(5.2)109.7(2.5)

95.3(5.7)

93.5(9.9)98.7(9.1)

3.98e-1

1.5e-4

98.8(4.3)84.2(11)

80.4(4.4)

93.2(3.7)

96.5(6.1)89.7(3.5)

92.7(15.8)

89.3(0.5)91.4(5)

81.3(4)

84.6(7.4)

79.4(2.5)

1.19

4.5e-4

62.5(5.1)

61.9(5.4)

64.9(0.7)

70.6(1.7)

57.8(2.1)

64.2(1.4)

1.33

5e-4

65(4.6)

55.3(3.4)

71.1(4.5)

53.5(1.6)

63.6(0.5)

64.6(1.8)

3.98

1.5e-3

28.5(5.1)

28.7(0.8)

26.9(1.5)

24.3(2.4)

34.6(2.4)

33.3(8.5)

28.5(5.2)

31.2(2.6)

30(2.6)

28.9(2.8)

31.2(1.3)

31.5(2.5)

11.95

4.5e-3

5.1(0.1)

4.3(0.6)

7(2.6)

7.5(0.9)

7.2(0.9)

7.5(0.1)

13.27

5e-3

3.7(0.5)

1.9(0.1)

6.5(0.5)

5.5(0.5)

5(1.5)

4.4(1.8)

39.82

1.5e-2

-1(0.1)

cyt/excl

cyt/excl

-0.2(0.2)

0(0.3)

-0.5(0.2)

R2

0.83

0.86

0.75

0.62

0.61

0.87

0.62

0.91

0.8

0.8

0.7

0.71

log 1

0(PC80)[mg/ml]

-3.55

-3.7

-3.81

-3.62

-3.45

-3.66

-3.57

-3.58

-3.56

-3.75

-3.71

-3.85

log 1

0(IC50)[mg/ml]

-3.13

-3.01

-3.04

-3.21

-3.05

-3.12

-3.14

-3.04

-3.06

-3.06

-3.11

-3.04


239

Citoxlab

Envigo

RISE

BDS

[mg/ml]

run10

run18

run22

run5

run6

run7

run13

run25

run31

run6

run8

run10

1.5e-6

240.3(6.4)

235(18.7)

190.3(6.3)

231.4(25.3)

254.3(4.9)

318.5(24.3)

4.5e-6

312.4(2.6)

241.7(22.4)

271.6(12.5)

281.4(15.5)218.8(7.1)

240.6(6.2)

5e-6

246(4.1)250.8(17)

148(15.1)

231.3(12.6)

242.3(7.3)

327.6(6.2)

1.5e-5

319.7(6.4)

215.5(23.3)

246.9(4.1)

274.3(10.8)

196.2(2.6)

246.7(13.3)

247.1(18.7)

241.9(6)

334.2(18.5)

264.7(18.6)213.4(10.8)

238.5(4.5)

4.5e-5

323.9(12.6)225.4(17.3)

232.5(23.1)

262.9(6)

208.6(10.3)

236.8(8.4)

5e-5

241.1(4)

288.4(20.3)

195.8(14.4)

248.5(12.3)

241.4(7.3)

333.1(8.2)

1.5e-4

311.1(11.3)229.2(7.1)243.6(9.7)

288.4(18.8)

179.2(2.5)

231.9(9.5)

260.1(19.6)

234.3(11.2)

329.4(18.3)

263.2(14.8)221.9(3.7)

236.7(5.8)

4.5e-4

300.4(13.3)213.3(3.4)

269.9(4.9)

280.4(12.5)212.4(6)

238.8(15.3)

5e-4

247.7(6.5)

204.1(35.4)

184.6(4.4)

217.1(24.8)

228.2(9.1)

316.5(13.6)

1.5e-3

263.3(12.5)

188.3(2.2)215.9(8)

253.8(17.5)

156.2(18.9)

200.1(12.4)

219(13.6)

193.6(10.7)287.6(14)

230.4(3.6)

185.8(9.1)

209.3(11.2)

4.5e-3

167(10.3)

124.9(3)

166.8(22.8)

97.7(4.9)

140.2(4.3)

155.7(5.1)

5e-3

137(2.4)

130.6(12.3)

101.8(3.8)

146.1(9)

132.5(3.2)

172.8(10.3)

1.5e-2

cyt/excl

cyt/excl

cyt/excl

47.5(3.3)

39.4(1.2)

39.1(2.6)



240

−8 −7 −6 −50

20

40

60

80

100

120

140

160

180

200

220

240

260

280

300

320

log10(M)

Rela

tive Induction [%

]


Citoxlab

Envigo

RISE

BDS

Flutamide


241

D.16 Test item 16

−11 −10 −9 −8 −7 −6 −5

20

40

60

80

100

120

140

160

180

200

220

240

260

280

log10(M)

Re

lative

In

du

ctio

n [

%]


−11 −10 −9 −8 −7 −6 −50

20

40

60

80

100

120

140

160

log10(M)

Re

lative

In

du

ctio

n [

%]


−11 −10 −9 −8 −7 −6 −5

20

40

60

80

100

120

140

160

180

200

log10(M)

Re

lative

In

du

ctio

n [

%]


−11 −10 −9 −8 −7 −6 −50

20

40

60

80

100

120

140

160

180

log10(M)

Re

lative

In

du

ctio

n [

%]


−11 −10 −9 −8 −7 −6 −5

20

40

60

80

100

120

140

160

log10(M)

Re

lative

In

du

ctio

n [

%]


−11 −10 −9 −8 −7 −6 −5

20

40

60

80

100

120

140

160

180

200

log10(M)

Re

lative

In

du

ctio

n [

%]


−11 −10 −9 −8 −7 −6 −5

20

40

60

80

100

120

140

160

180

200

log10(M)

Re

lative

In

du

ctio

n [

%]


−11 −10 −9 −8 −7 −6 −50

20

40

60

80

100

120

140

log10(M)

Re

lative

In

du

ctio

n [

%]


−11 −10 −9 −8 −7 −6 −50

20

40

60

80

100

120

140

160

log10(M)

Re

lative

In

du

ctio

n [

%]


−11 −10 −9 −8 −7 −6 −5

20

40

60

80

100

120

140

160

180

200

log10(M)

Re

lative

In

du

ctio

n [

%]


−11 −10 −9 −8 −7 −6 −50

20

40

60

80

100

120

140

log10(M)

Re

lative

In

du

ctio

n [

%]


−11 −10 −9 −8 −7 −6 −5

20

40

60

80

100

120

140

160

180

200

log10(M)

Re

lative

In

du

ctio

n [

%]




242

−11 −10 −9 −8 −7 −6 −50

20

40

60

80

100

120

140

160

180

200

220

240

260

log10(M)

Rela

tive Induction [%

]

TI−CIT2YW, Citoxlab

run 3

run 12

run 14

Flutamide

−11 −10 −9 −8 −7 −6 −50

20

40

60

80

100

120

140

160

180

200

log10(M)

Rela

tive Induction [%

]

TI−ENV3DX, Envigo

run 2

run 3

run 8

Flutamide

−11 −10 −9 −8 −7 −6 −50

20

40

60

80

100

120

140

160

180

log10(M)

Rela

tive Induction [%

]

TI−03FA, RISE

run 1

run 7

run 9

Flutamide

−11 −10 −9 −8 −7 −6 −50

20

40

60

80

100

120

140

160

180

200

log10(M)

Rela

tive Induction [%

]

TI−BDS2BG, BDS

run 1

run 3

run 4

Flutamide


243

Citoxlab

Envigo

RISE

BDS

run3

run12

run14

run2

run3

run8

run1

run7

run9

run1

run3

run4

[µM]

[mg/ml]

PRE

PRE

PRE

PRE

PRE

PRE

PRE

PRE

PRE

PRE

PRE

PRE

1.49e-6

5e-10

101.2(7.8)113.7(0.8)

97.8(4.8)

99.8(7.7)84.4(6.2)

97.4(4.5)

96.9(7.7)

93.9(9.8)105.7(5.5)

4.46e-6

1.5e-9

97.9

(4)

87.9(3.4)

110(4.8)

1.49e-5

5e-9

106.1(7.9)112.9(2.8)

86.7(5.6)

106.6(3.5)

83.6(9.3)

98.8(3.9)

99.7(12.5)

93.8(5.3)102.5(4.3)

4.46e-5

1.5e-8

94.3

(5)

84.3(6)

104.2(7.2)

1.49e-4

5e-8

100.4(7.8)

89.5(8.5)

96.2(10.8)

106.6(2.2)

83.3(1.6)105.1(7.8)

94.4(11)

95(2.9)102.8(7.9)

4.46e-4

1.5e-7

111.5(6)

88.9(3.4)105.2(7.9)

1.49e-3

5e-7

88.6(3.3)100.7(12.1)93.1(1.7)

102.7(6.9)

76.4(7.9)103.8(1.5)

95.6(13.3)

91.8(6.4)111.7(6.6)

4.46e-3

1.5e-6

160.5(9.7)104.3(2.7)

111.5(17.8)

1.49e-2

5e-6

119.9(5.5)119.1(9.8)123.7(10.7)127.4(8)

94.2(10.2)

121.4(5.7)

130.5(20.2)111.6(3.9)

142(5)

4.46e-2

1.5e-5

189.1(12.9)127.4(6.3)

140.2(19.8)

1.49e-1

5e-5

122.9(4.1)125.4(16.5)135.2(11.2)141.3(5.2)

105.2(11.4)128.3(4)

152.6(21.6)

122(0.5)165.9(7.4)

4.46e-1

1.5e-4

207.4(16)

125.5(5.6)

123.1(27.5)

1.49

5e-4

136.3(20.3)167.1(2.1)154.7(13.4)151.7(9.1)

111.9(7.8)139.7(8)

166.1(17.2)123.6(8.5)

183.2(8.5)

4.46

1.5e-3

227.2(8.1)

146(6.3)160.5(23.8)

14.86

5e-3

169.4(16.9)

160(10.4)

202.1(9.9)

194.6(9.5)

135.3(13.2)173.5(6.3)

202.5(19.6)151.2(4)

204.4(5.6)

44.59

1.5e-2

273.7(13)

161.3(9.1)

177.9(22.6)

R2

log 1

0(PC80)[mg/ml]

-6.97

log 1

0(IC50)[mg/ml]

-2.73


244

−11 −10 −9 −8 −7 −6 −50

20

40

60

80

100

120

140

160

180

200

220

240

260

log10(M)

Rela

tive Induction [%

]


Citoxlab

Envigo

RISE

BDS

Flutamide


245

D.17 Test item 17

−8 −7 −6 −50

20

40

60

80

100

120

140

160

180

200

220

240

260

280

log10(M)

Rela

tive Induction [%

]TI−CIT2ML, run 11, Citoxlab

−10 −9 −8 −7 −6 −50

20

40

60

80

100

120

140

160

180

200

220

240

260

log10(M)

Rela

tive Induction [%

]


−10 −9 −8 −7 −6 −50

20

40

60

80

100

120

140

160

180

200

220

240

log10(M)

Rela

tive Induction [%

]


−10 −9 −8 −7 −6 −5

20

40

60

80

100

120

140

160

180

200

220

240

260

log10(M)

Rela

tive Induction [%

]


−10 −9 −8 −7 −6 −50

20

40

60

80

100

120

140

160

180

200

220

240

log10(M)

Rela

tive Induction [%

]TI−ENV3PU, run 10, Envigo

−10 −9 −8 −7 −6 −50

20

40

60

80

100

120

140

160

180

200

log10(M)

Rela

tive Induction [%

]


−9 −8 −7 −6 −50

20

40

60

80

100

120

140

160

180

200

220

log10(M)

Rela

tive Induction [%

]


−9 −8 −7 −6 −5

20

40

60

80

100

120

140

160

180

200

220

log10(M)

Rela

tive Induction [%

]


−9 −8 −7 −6 −50

20

40

60

80

100

120

140

160

180

200

220

240

260

280

300

320

log10(M)

Rela

tive Induction [%

]


−9 −8 −7 −6 −5

20

40

60

80

100

120

140

160

180

200

220

240

260

280

300

log10(M)

Rela

tive Induction [%

]


−9 −8 −7 −6 −50

20

40

60

80

100

120

140

160

180

200

220

log10(M)

Rela

tive Induction [%

]


−9 −8 −7 −6 −5

20

40

60

80

100

120

140

160

180

200

220

240

260

280

log10(M)

Rela

tive Induction [%

]




246

−8 −7 −6 −50

20

40

60

80

100

120

log10(M)

Rela

tive Induction*

[%]


−10 −9 −8 −7 −6 −50

20

40

60

80

100

120

140

160

180

log10(M)R

ela

tive Induction*

[%]


−10 −9 −8 −7 −6 −50

20

40

60

80

100

log10(M)

Rela

tive Induction*

[%]


−10 −9 −8 −7 −6 −5

20

40

60

80

100

log10(M)

Rela

tive Induction*

[%]


−10 −9 −8 −7 −6 −50

20

40

60

80

100

log10(M)

Rela

tive Induction*

[%]


−10 −9 −8 −7 −6 −50

20

40

60

80

100

log10(M)

Rela

tive Induction*

[%]


−9 −8 −7 −6 −50

20

40

60

80

100

log10(M)

Rela

tive Induction*

[%]


−9 −8 −7 −6 −5

20

40

60

80

100

log10(M)

Rela

tive Induction*

[%]


−9 −8 −7 −6 −50

20

40

60

80

100

log10(M)

Rela

tive Induction*

[%]TI−32BL, run 31, RISE

−9 −8 −7 −6 −5

20

40

60

80

100

log10(M)

Rela

tive Induction*

[%]


−9 −8 −7 −6 −50

20

40

60

80

100

log10(M)

Rela

tive Induction*

[%]


−9 −8 −7 −6 −5

20

40

60

80

100

120

log10(M)

Rela

tive Induction*

[%]





247

−10 −9 −8 −7 −6 −50

20

40

60

80

100

120

140

160

180

200

220

240

260

280

log10(M)

Rela

tive Induction [%

]

TI−CIT2ML, Citoxlab

run 11

run 18

run 21

Flutamide

−10 −9 −8 −7 −6 −50

20

40

60

80

100

120

140

160

180

200

220

240

log10(M)

Rela

tive Induction [%

]

TI−ENV3PU, Envigo

run 9

run 10

run 11

Flutamide

−9 −8 −7 −6 −50

20

40

60

80

100

120

140

160

180

200

220

240

260

280

300

log10(M)

Rela

tive Induction [%

]

TI−32BL, RISE

run 20

run 22

run 31

Flutamide

−9 −8 −7 −6 −50

20

40

60

80

100

120

140

160

180

200

220

240

260

280

log10(M)

Rela

tive Induction [%

]

TI−BDS2UE, BDS

run 6

run 10

run 12

Flutamide


248

Citoxlab

Envigo

RISE

BDS

run11

run18

run21

run9

run10

run11

run20

run22

run31

run6

run10

run12

[µM]

[mg/ml]

COM

COM

COM

COM

COM

COM

COM

COM

COM

COM

COM

COM

7.05e-5

1.92e-8

98.9(9.2)94.8(3.4)

9.91e-5

2.7e-8

103.5(0.9)

100.3(6.6)

93.7(4.3)

1.65e-4

4.5e-8

96.8(6.7)84.9(7.3)90.7(7.6)

3.3e-4

9e-8

94.1(7.6)96.4(6.8)97.4(14.1)

3.52e-4

9.6e-8

89.2(7.2)87.9(2.4)

4.96e-4

1.35e-7

95.3(2.2)86.1(2.7)

119(11.2)

5.51e-4

1.5e-7

87.7(3.7)89.8(3.8)88.8(10.8)

9.91e-4

2.7e-7

90.6(1.6)88.8(2.9)96.9(10.2)

1.65e-3

4.5e-7

89.2(4.7)

82.1(1.9)81.2(6.5)

78.4(4.1)

82.4(2.9)

74.9(1.9)106.7(3.7)

1.76e-3

4.8e-7

79.7(1.8)

75.9(8.6)

3.3e-3

9e-7

78.6(3.8)80.8(2.9)

90(1.6)

4.96e-3

1.35e-6

71.6(2.5)

64.3(1.6)91.5(3.5)

5.51e-3

1.5e-6

72.5(4.4)

66.6(1.5)

66(2.2)

64(5.2)

8.81e-3

2.4e-6

55.1(3.7)

51.3(0.6)

9.91e-3

2.7e-6

59.5(4)

63.1(0.9)

74.1(3.6)

1.65e-2

4.5e-6

50.8(1.4)

47.5(1.8)

47.9(2.5)

49.8(1.9)

50.4(1.1)

46.5(1.2)

66.6(0.9)

3.3e-2

9e-6

41.8(2.6)

43.2(1.5)

51.2(4.5)

4.41e-2

1.2e-5

30.5(1.2)

31.6(1.3)

4.96e-2

1.35e-5

35.5(2.4)

31.3(1.4)

42.8(3.3)

5.51e-2

1.5e-5

34.8(1.6)

30.6(1.1)

31(2.4)

35.8(3)

9.91e-2

2.7e-5

46.1(5.3)

30.1(2.6)

30.5(1.7)

1.65e-1

4.5e-5

24.4(2.1)

21.3(1.4)

25.8(1.4)

28.5(1.1)

26(1.8)

20.4(0.7)

29.6(1.8)

2.2e-1

6e-5

19.2(1.2)

19.2(1.7)

3.3e-1

9e-5

22.6(1.3)

23.6(1.7)

22.6(2.2)

4.96e-1

1.35e-4

27.6(4)

21(0.4)

26.9(0.9)

5.51e-1

1.5e-4

25.3(1)

21.8(1)

25.4(2.9)

31.8(1)

1.1

3e-4

30.6(6.9)

25.1(0.7)

1.65

4.5e-4

31.2(1.2)

37.1(2.6)

28(1)

33.1(1.5)

5.51

1.5e-3

54.3(1.6)

50.5(1.6)

54.6(4.5)

R2

0.11

0.22

0.17

0.56

0.47

0.58

0.51

0.61

0.44

0.33

0.5

0.47

log 1

0(PC80)[mg/ml]

-6-6.33

-6.49

-6.09

-6.02

-5.72

-6.25

-6.3

-6.41

-6.21

-6.61

-5.61

log 1

0(IC50)[mg/ml]

-5.62

-5.89

-5.96

-5.54

-5.47

-5.2

-5.61

-5.57

-5.72

-5.69

-5.62

-5.53


249

Citoxlab

Envigo

RISE

BDS

[mg/ml]

run11

run18

run21

run9

run10

run11

run20

run22

run31

run6

run10

run12

1.92e-8

247(16.3)

246.2(7.7)

2.7e-8

256(9)

227.3(9.1)

187.4(11.8)

4.5e-8

223(10.6)

213.4(8.1)

309.1(22.5)

9e-8

241.3(12.2)

237(2.8)

195.6(6.3)

9.6e-8

243.7(5)

241.4(8.3)

1.35e-7

279.6(4)

225.5(14.7)

255.6(13.6)

1.5e-7

216.8(6.7)

212.4(7)

317(11.7)

2.7e-7

246.4(8.5)233.4(5)

200.8(10.7)

4.5e-7

286.4(10.2)

221.6(5.2)

210.7(3.5)

313(8.6)

290.2(23.5)

229.8(6.9)

261.9(32.7)

4.8e-7

245.5(5.5)

242.5(7.5)

9e-7

257.3(14.3)241.5(5.3)

184.9(24)

1.35e-6

275.7(13)

222.6(1.1)

252.2(12.5)

1.5e-6

287.4(6.7)

211.5(5.8)

203.4(14.5)

312.7(23.1)

2.4e-6

248.4(9.8)

246.8(13.7)

2.7e-6

235.3(11.7)235.2(8)

199.3(3.6)

4.5e-6

285.6(2.6)

208.7(6.1)

204.1(8.8)

317(9.6)

285.4(10.4)

220.6(8.7)

253.3(10.9)

9e-6

248.7(15.5)241.2(14.9)179.3(24.7)

1.2e-5

235.1(4.5)

232.6(3.8)

1.35e-5

277.4(10.4)

203.4(8.1)

246.7(24)

1.5e-5

269.8(8.6)

213.9(8.2)

196.2(4.5)

302.5(22.2)

2.7e-5

225.7(10.9)198.7(5.7)

179.2(6.2)

4.5e-5

257.5(5.2)

196.8(7.3)

180.4(4.4)

259.7(3.6)

245.4(18.3)

193.7(2.4)

221.2(12.3)

6e-5

199.3(9.4)

204.3(11.5)

9e-5

208.3(12.4)190.2(5.6)

122.8(27.1)

1.35e-4

218.9(5.5)

160.9(4.5)

185.7(6.6)

1.5e-4

207.3(12.7)

158.7(2.3)

145.5(2.1)

211.3(12.1)

3e-4

133.1(7)

130.9(6.5)

4.5e-4

154.9(4.1)

166.5(7.2)

121.6(3.5)

130.4(4.3)

1.5e-3

111.7(3.7)

89.5(3.6)

85.4(4.8)



250

−10 −9 −8 −7 −6 −50

20

40

60

80

100

120

140

160

180

200

220

240

260

280

300

log10(M)

Rela

tive Induction [%

]


Citoxlab

Envigo

RISE

BDS

Flutamide


251

D.18 Test item 18

−8 −7 −6 −5

20

40

60

80

100

120

140

160

180

200

220

240

260

280

log10(M)

Re

lative

In

du

ctio

n [

%]


−8 −7 −6 −50

20

40

60

80

100

120

140

160

180

200

220

240

260

log10(M)

Re

lative

In

du

ctio

n [

%]


−8 −7 −6 −5

20

40

60

80

100

120

140

160

180

200

220

240

260

log10(M)

Re

lative

In

du

ctio

n [

%]


−8 −7 −6 −5 −40

20

40

60

80

100

120

140

160

180

200

220

240

260

log10(M)

Re

lative

In

du

ctio

n [

%]


−8 −7 −6 −5 −40

20

40

60

80

100

120

140

160

180

log10(M)

Re

lative

In

du

ctio

n [

%]


−8 −7 −6 −5 −40

20

40

60

80

100

120

140

160

180

200

220

240

260

280

log10(M)

Re

lative

In

du

ctio

n [

%]


−8 −7 −6 −5

20

40

60

80

100

120

140

160

180

200

220

log10(M)

Rela

tive Induction [%

]


−8 −7 −6 −50

20

40

60

80

100

120

140

160

180

200

220

240

260

280

log10(M)

Rela

tive Induction [%

]


−8 −7 −6 −5

20

40

60

80

100

120

140

160

180

200

220

log10(M)

Rela

tive Induction [%

]


−8 −7 −6 −5 −40

20

40

60

80

100

120

140

160

180

200

220

240

log10(M)

Re

lative

In

du

ctio

n [

%]


−8 −7 −6 −5 −40

20

40

60

80

100

120

140

160

180

200

220

240

260

log10(M)

Re

lative

In

du

ctio

n [

%]


−8 −7 −6 −5 −40

20

40

60

80

100

120

140

160

180

200

220

240

260

log10(M)

Re

lative

In

du

ctio

n [

%]




252

−8 −7 −6 −5

20

40

60

80

100

log10(M)

Re

lative

In

du

ctio

n*

[%]


−8 −7 −6 −50

20

40

60

80

100

log10(M)R

ela

tive

In

du

ctio

n*

[%]


−8 −7 −6 −5

20

40

60

80

100

log10(M)

Re

lative

In

du

ctio

n*

[%]


−8 −7 −6 −5 −40

20

40

60

80

100

log10(M)

Re

lative

In

du

ctio

n*

[%]


−8 −7 −6 −5 −40

20

40

60

80

100

120

log10(M)

Re

lative

In

du

ctio

n*

[%]


−8 −7 −6 −5 −40

20

40

60

80

100

120

log10(M)

Re

lative

In

du

ctio

n*

[%]


−8 −7 −6 −5

20

40

60

80

100

log10(M)

Rela

tive Induction*

[%]


−8 −7 −6 −50

20

40

60

80

100

log10(M)

Rela

tive Induction*

[%]


−8 −7 −6 −5

20

40

60

80

100

log10(M)

Re

lative

In

du

ctio

n*

[%]

TI−30QT, run 25, RISE, int=68.21

−8 −7 −6 −5 −40

20

40

60

80

100

log10(M)

Re

lative

In

du

ctio

n*

[%]


−8 −7 −6 −5 −40

20

40

60

80

100

120

log10(M)

Re

lative

In

du

ctio

n*

[%]


−8 −7 −6 −5 −40

20

40

60

80

100

log10(M)

Re

lative

In

du

ctio

n*

[%]





253

−8 −7 −6 −50

20

40

60

80

100

120

140

160

180

200

220

240

260

280

log10(M)

Rela

tive Induction [%

]

TI−CIT2PY, Citoxlab

run 10

run 19

run 22

Flutamide

−8 −7 −6 −5 −40

20

40

60

80

100

120

140

160

180

200

220

240

260

log10(M)

Rela

tive Induction [%

]

TI−ENV3KU, Envigo

run 5

run 6

run 7

Flutamide

−8 −7 −6 −50

20

40

60

80

100

120

140

160

180

200

220

240

260

log10(M)

Rela

tive Induction [%

]

TI−30QT, RISE

run 13

run 16

run 25

Flutamide

−8 −7 −6 −5 −40

20

40

60

80

100

120

140

160

180

200

220

240

log10(M)

Rela

tive Induction [%

]

TI−BDS2CM, BDS

run 10

run 11

run 12

Flutamide


254

Citoxlab

Envigo

RISE

BDS

run10

run19

run22

run5

run6

run7

run13

run16

run25

run10

run11

run12

[µM]

[mg/ml]

COM

COM

COM

COM

COM

COM

COM

COM

COM

COM

COM

COM

1.44e-3

4.5e-7

91.9(10)

99.5(10.6)

98.5

(1.1)

4.8e-3

1.5e-6

85.5(8.4)103.8(1.1)100.6(1.9)

1.44e-2

4.5e-6

95.3(4.4)101.5(5.5)

89.6(0.4)

88.3(6.7)

95.9(1.9)

99.1

(5.1)

4.32e-2

1.35e-5

101.3(3.3)

107.9(3.9)

cyt/excl

4.8e-2

1.5e-5

93.7(5.7)96.1(2.1)85.4(7.9)

64.9(15.3)

103.3(4.4)104.7(14.4)

75.8(2.4)102.7(7.4)

93.6

(3.2)

1.44e-1

4.5e-5

89.7(4.6)95.5(5)

86.2(8.9)

82.4(13.4)

101.1(7.7)

93.9

(3.7)

94.6(2)

109.3(3.9)107.2(2.8)

1.6e-1

5e-5

94.1(21)

82.8(12.1)

97.1(12.8)

4.32e-1

1.35e-4

89.2(2.7)112.6(7.7)102.5(1.7)

4.8e-1

1.5e-4

93.1(3.4)96.5(2.2)84.4(7.9)84.1(7.4)

93.2(9.5)102.2(2.8)

78.2(4.2)

95(3.9)

99.7

(2.8)

1.44

4.5e-4

77.5(3.2)88.8(3.4)

71.2(1.8)

73.7(2.6)

78.6(3.5)

83(4)

80.1(2.3)101.5(7.1)

96(1.9)

1.6

5e-4

76.2(7.5)

83.3(3.3)

97.3(2.5)

4.32

1.35e-3

47.9(1.8)

72.6(13.1)

64.2(3.1)

4.8

1.5e-3

48.8(2.4)

50(4.5)

54.5(6.3)

55.7(4)

48.8(2)

68.3(9.2)

47.7(6.1)

50.7(1.8)

48.1

(1.8)

14.4

4.5e-3

14.2(0.6)

16(1.2)

21.3(1.2)

18.4(0.5)

27.5(0.9)

26.9(1.3)

16.01

5e-3

17(2.9)

16.6(0.9)

26.1(2.3)

43.21

1.35e-2

4.7(0.3)

8.8(0.3)

7.1(0.5)

48.02

1.5e-2

1.7(0.2)

3.7(1)

3.9(0.4)

5.9(3.1)

2.9(0.6)

5(0.5)

144.05

4.5e-2

3.1(0.1)

4.6(0.3)

4(0.2)

160.05

5e-2

1.2(0.7)

3(0.3)

2(0.4)

interpvalue(x,y)

(7.5e-4,68.2)

R2

0.69

0.7

0.7

0.69

0.74

0.83

0.1

0.2

0.6

0.68

0.66

0.78

log 1

0(PC80)[mg/ml]

-3.4

-3.2

-3.64

-3.55

-3.24

-2.98

na-3.38

-3.3

-3.34

-2.97

-3.08

log 1

0(IC50)[mg/ml]

-2.8

-2.82

-2.63

-2.65

-2.8

-2.62

na-3.19

-3.32

-2.88

-2.7

-2.74


255

Citoxlab

Envigo

RISE

BDS

[mg/ml]

run10

run19

run22

run5

run6

run7

run13

run16

run25

run10

run11

run12

4.5e-7

212.5(4.8)267.3(25)

215.5(9.8)

1.5e-6

199(2.5)272.9(21)

211.8(14.4)

4.5e-6

266.9(3)

236(18.3)

256(15)

213.6(11)

256.1(10.7)213.7(5.8)

1.35e-5

241(14.7)

237.9(3.8)

245.5(7)

1.5e-5

270.8(2.3)

246.4(12.4)

268.6(8.7)

245.2(16.6)

157.4(21.5)241.9(16.8)

193.6(13.9)264.6(15.2)215.4(10.4)

4.5e-5

278.3(16.3)

247.6(13.9)

252.6(8.7)

201.5(4.2)261.1(8.6)218.3(5.7)

248.4(3.8)

242(9.4)

242.8(8.7)

5e-5

237.4(56.5)

185.6(9.1)

240.6(6.4)

1.35e-4

251.9(5.6)

231.7(15.8)

245.6(8.4)

1.5e-4

281(3.5)

233.1(7.2)

253.8(15.2)

228.1(28.7)

191.9(9.1)

269.6(23.7)

202.5(8.9)275.1(13.8)214.7(10.8)

4.5e-4

272.2(5.4)

229(5.9)

247.3(5)

212.8(15.5)268.6(12.7)217.4(3)

241.4(17.7)

229.4(7.8)

257.6(3.8)

5e-4

253.5(0.8)172.9(21.5)251.4(15.7)

1.35e-3

244.2(4.9)

253.4(8.1)

244.3(4.9)

1.5e-3

267.8(4.5)

232.8(11.7)

266.2(7.6)

249.3(24.5)

164.9(9.3)

255.5(17.3)

217.5(12.5)275.4(12.1)219.8(3.2)

4.5e-3

230.3(20.9)

209.3(14.4)

223.7(8.4)

223.5(13)

222.9(10.9)

217.6(2.4)

5e-3

213(30.4)

137.9(7.4)

198.7(7.1)

1.35e-2

142.2(13)

157.1(5.1)

145.4(5.9)

1.5e-2

127.7(7.6)

149.5(13.1)

148.6(2)

129.1(7)

74.7(6.8)

129.5(20.9)

4.5e-2

118.1(9)

130.2(18.2)

134.8(4.8)

5e-2

120.3(12.6)

59.7(4.7)

91.2(15.8)



256

−8 −7 −6 −5 −40

20

40

60

80

100

120

140

160

180

200

220

240

260

280

log10(M)

Rela

tive Induction [%

]


Citoxlab

Envigo

RISE

BDS

Flutamide


257

D.19 Test item 19

−8 −7 −6 −5 −4

20

40

60

80

100

120

140

160

180

200

220

240

260

280

300

log10(M)

Re

lative

In

du

ctio

n [

%]


−8 −7 −6 −5 −40

20

40

60

80

100

120

140

160

180

200

220

240

260

log10(M)

Re

lative

In

du

ctio

n [

%]


−8 −7 −6 −5 −40

20

40

60

80

100

120

140

160

180

200

220

240

260

log10(M)

Re

lative

In

du

ctio

n [

%]


−10 −9 −8 −7 −6 −5 −4

20

40

60

80

100

log10(M)

Re

lative

In

du

ctio

n [

%]


−10 −9 −8 −7 −6 −5 −40

20

40

60

80

100

log10(M)

Re

lative

In

du

ctio

n [

%]


−10 −9 −8 −7 −6 −5 −4

20

40

60

80

100

120

log10(M)

Re

lative

In

du

ctio

n [

%]


−8 −7 −6 −5 −40

20

40

60

80

100

120

140

160

180

200

220

240

log10(M)

Re

lative

In

du

ctio

n [

%]


−8 −7 −6 −5 −4

20

40

60

80

100

120

140

160

180

200

220

240

log10(M)

Re

lative

In

du

ctio

n [

%]


−8 −7 −6 −5 −40

20

40

60

80

100

120

140

160

180

200

220

240

260

280

300

320

340

360

380

log10(M)

Re

lative

In

du

ctio

n [

%]


−8 −7 −6 −5 −40

20

40

60

80

100

120

140

160

180

200

220

240

260

280

300

log10(M)

Rela

tive Induction [%

]


−8 −7 −6 −5 −40

20

40

60

80

100

120

140

160

180

200

log10(M)

Rela

tive Induction [%

]


−8 −7 −6 −5 −40

20

40

60

80

100

120

140

160

180

200

220

240

260

log10(M)

Rela

tive Induction [%

]




258

−8 −7 −6 −5 −4

20

40

60

80

100

log10(M)

Re

lative

In

du

ctio

n*

[%]

TI−CIT2HZ, run 9, Citoxlab, int=83.58

−8 −7 −6 −5 −40

20

40

60

80

100

log10(M)R

ela

tive

In

du

ctio

n*

[%]


−8 −7 −6 −5 −40

20

40

60

80

100

log10(M)

Re

lative

In

du

ctio

n*

[%]

TI−CIT2HZ, run 20, Citoxlab, int=83.42

−10 −9 −8 −7 −6 −5 −4

20

40

60

80

100

log10(M)

Re

lative

In

du

ctio

n*

[%]

TI−ENV3CK, run 1, Envigo, int=74.15

−10 −9 −8 −7 −6 −5 −40

20

40

60

80

100

log10(M)

Re

lative

In

du

ctio

n*

[%]


−10 −9 −8 −7 −6 −5 −4

20

40

60

80

100

120

log10(M)

Re

lative

In

du

ctio

n*

[%]

TI−ENV3CK, run 3, Envigo, int=80.49

−8 −7 −6 −5 −40

20

40

60

80

100

log10(M)

Re

lative

In

du

ctio

n*

[%]

TI−20WZ, run 20, RISE, int=87.71

−8 −7 −6 −5 −4

20

40

60

80

100

log10(M)

Re

lative

In

du

ctio

n*

[%]

TI−20WZ, run 25, RISE, int=83.05

−8 −7 −6 −5 −40

20

40

60

80

100

log10(M)

Re

lative

In

du

ctio

n*

[%]


−8 −7 −6 −5 −40

20

40

60

80

100

120

140

log10(M)

Rela

tive Induction*

[%]


−8 −7 −6 −5 −40

20

40

60

80

100

log10(M)

Re

lative

In

du

ctio

n*

[%]

TI−BDS2NZ, run 7, BDS, int=80.47

−8 −7 −6 −5 −40

20

40

60

80

100

log10(M)

Rela

tive Induction*

[%]





259

−8 −7 −6 −5 −40

20

40

60

80

100

120

140

160

180

200

220

240

260

280

log10(M)

Rela

tive Induction [%

]


run 9

run 16

run 20

Flutamide

−10 −9 −8 −7 −6 −5 −40

20

40

60

80

100

log10(M)

Rela

tive Induction [%

]

TI−ENV3CK, Envigo

run 1

run 2

run 3

Flutamide

−8 −7 −6 −5 −40

20

40

60

80

100

120

140

160

180

200

220

240

260

280

300

320

340

log10(M)

Rela

tive Induction [%

]

TI−20WZ, RISE

run 20

run 25

run 34

Flutamide

−8 −7 −6 −5 −40

20

40

60

80

100

120

140

160

180

200

220

240

260

280

300

log10(M)

Rela

tive Induction [%

]

TI−BDS2NZ, BDS

run 5

run 7

run 9

Flutamide


260

Citoxlab

Envigo

RISE

BDS

run9

run16

run20

run1

run2

run3

run20

run25

run34

run5

run7

run9

[µM]

[mg/ml]

COM

COM

COM

PRE

PRE

PRE

COM

COM

COM

COM

COM

COM

2.94e-5

5e-9

100.4

(9)

101.9(5.9)100.9(5.2)

2.94e-4

5e-8

85.5

(6.6)

97.3(8.2)

99.8

(7.2)

2.94e-3

5e-7

97.3(10.7)

108.7(5.8)

100(6.5)

2.94e-2

5e-6

97.9

(4.5)

102.1(12.1)102.3(33.9)

8.81e-2

1.5e-5

98.5

(5.9)

92.8(5.6)94.3

(5.3)

101.9(6.8)

97.2

(3)

91(6.1)

2.64e-1

4.5e-5

117.3(12.3)95.6

(1.7)

95(4.1)

2.94e-1

5e-5

99.4

(6.7)

91.8(3)

97.2

(2.5)

96.2

(8.2)

112.3(7.9)

97.8

(7.8)

102.3(6.4)

97.6(1.2)

106.8(5.4)

8.81e-1

1.5e-4

100.5(1.6)

100.7(3.9)

99.3

(5.2)

100.7(2.6)

96(4.5)

99.7(4.9)122.1(5.8)

92.1

(5.4)

96(5.1)

2.64

4.5e-4

116.8(3.1)

91.5

(6.1)

94.1(4)

2.94

5e-4

104.1(7.9)

96.9(3.4)91.7

(4.1)

94.9(11.7)

102.2(0.8)

88.3

(4.4)

94.9

(5.5)

96.2(8.6)

94.4(5.4)

8.81

1.5e-3

101.2(8.8)

93.6(4.5)94.7

(5.1)

100.6(3.8)

97.4(5.9)

102.1(8.4)

117.3(12.2)91.3

(2.7)

91.3(1.8)

26.44

4.5e-3

135.9(7.1)

91.7

(2)

92.7(2.6)

29.38

5e-3

102.1(3.1)

93.5(3.1)97.3

(3.6)

92.5(15.2)

100.2(4.7)101.2(9.3)

95(5.1)

92.5(3.6)

93.4(3.6)

88.13

1.5e-2

94.2

(3.5)

99(1.6)87.8

(6.9)

94.3

(1.9)

88(5)

90.8(7.1)107.2(9.7)

84.4

(3.6)

89(4)

264.39

4.5e-2

98.4(2.9)

73.8

(3)

81.5(3.5)

293.77

5e-2

69.1(4.4)

84.3(2.3)

77.5(2.6)

66.3

(9)

82.9(4.8)

71.6(5.7)

78.8(4.2)

76.4(1.7)

81.7(3.2)

881.32

1.5e-1

cyt/excl

cyt/excl

cyt/excl

interpvalue(x,y)

(2.5e-2,83.6)

(2.5e-2,83.4)

(2.5e-2,74.1)

(2.5e-2,80.5)(2.5e-2,87.7)(2.5e-2,83)

(2.25e-2,80.5)

R2

0.39

0.07

0.03

0.36

0.4

0.52

0.12

0.24

0.22

log 1

0(PC80)[mg/ml]

-1.48

-1.49

-1.65

-1.42

-1.32

-1.41

-1.62

log 1

0(IC50)[mg/ml]

-1.78

-1.82

nana

nana

-1.53


261

Citoxlab

Envigo

RISE

BDS

[mg/ml]

run9

run16

run20

run1

run2

run3

run20

run25

run34

run5

run7

run9

5e-9

5e-8

5e-7

5e-6

1.5e-5

280(10.9)

253.5(4.7)243.1(15.2)

230.6(6.4)240.6(8.6)346.8(11.2)

4.5e-5

282.3(28.5)199.1(3)

252.6(4.7)

5e-5

285.1(10.7)

248(29.9)

239.8(7.9)

226.6(8.9)228.6(4.8)350.5(27.8)

1.5e-4

293.9(5.4)254.1(18.2)239.6(22)

219.2(8.6)228.3(3.7)352.2(10.5)280.3(18.2)

192(0.5)241.5(9.3)

4.5e-4

291.7(9.3)186.7(16.3)237.9(5.9)

5e-4

289.9(9.3)256.4(4.2)246.8(8.6)

223.6(13.1)221.3(0.6)328.8(17.4)

1.5e-3

270.9(13.5)255.7(6.9)239.8(7.2)

221.7(4.8)231.9(8.2)342.7(11)

293.4(4.7)193.4(6.2)231.5(11)

4.5e-3

310.1(6.2)203.6(12.1)242.3(8.5)

5e-3

276.9(9.4)249.9(7)

240.1(11.6)

221(6.7)222.4(4.2)

338(7.2)

1.5e-2

266.7(14.2)256.8(5.6)242.6(6.4)

218.7(20.6)229.2(12.8)345.4(4.3)

289.5(14.2)200.2(14.3)243.9(19)

4.5e-2

295.3(19.8)

184(8.1)234.5(15.2)

5e-2

264.9(7.3)261.8(3.8)240.5(8.5)

217.8(12)

216.2(3.9)315.2(8.8)

1.5e-1

cyt/excl

cyt/excl

cyt/excl



262

−10 −9 −8 −7 −6 −5 −40

20

40

60

80

100

120

140

160

180

200

220

240

260

280

300

320

340

log10(M)

Rela

tive Induction [%

]


Citoxlab

Envigo

RISE

BDS

Flutamide


263

D.20 Test item 20

−8 −7 −6 −50

20

40

60

80

100

120

140

160

180

200

220

240

260

280

log10(M)

Rela

tive Induction [%

]TI−CIT2TF, run 11, Citoxlab

−8 −7 −6 −5

20

40

60

80

100

120

140

160

180

200

220

240

log10(M)

Rela

tive Induction [%

]


−8 −7 −6 −50

20

40

60

80

100

120

140

160

180

200

220

240

260

log10(M)

Rela

tive Induction [%

]


−9 −8 −7 −6 −50

20

40

60

80

100

120

140

160

180

200

220

log10(M)

Rela

tive Induction [%

]


−9 −8 −7 −6 −5

20

40

60

80

100

120

140

160

180

200

220

240

260

280

300

log10(M)

Rela

tive Induction [%

]TI−ENV3EH, run 9, Envigo

−9 −8 −7 −6 −50

20

40

60

80

100

120

140

160

180

200

220

240

260

log10(M)

Rela

tive Induction [%

]


−9 −8 −7 −6 −50

20

40

60

80

100

120

140

160

180

200

log10(M)

Rela

tive Induction [%

]


−9 −8 −7 −6 −5

20

40

60

80

100

120

140

160

180

200

220

240

log10(M)

Rela

tive Induction [%

]


−9 −8 −7 −6 −50

20

40

60

80

100

120

140

160

180

200

220

240

260

280

log10(M)

Rela

tive Induction [%

]


−8 −7 −6 −50

20

40

60

80

100

120

140

160

180

200

220

240

log10(M)

Rela

tive Induction [%

]


−8 −7 −6 −5

20

40

60

80

100

120

140

160

180

200

log10(M)

Rela

tive Induction [%

]


−8 −7 −6 −50

20

40

60

80

100

120

140

160

180

200

220

240

log10(M)

Rela

tive Induction [%

]




264

−8 −7 −6 −50

20

40

60

80

100

120

log10(M)

Rela

tive Induction*

[%]


−8 −7 −6 −5

20

40

60

80

100

log10(M)R

ela

tive Induction*

[%]


−8 −7 −6 −50

20

40

60

80

100

log10(M)

Rela

tive Induction*

[%]


−9 −8 −7 −6 −50

20

40

60

80

100

120

log10(M)

Rela

tive Induction*

[%]


−9 −8 −7 −6 −5

20

40

60

80

100

log10(M)

Rela

tive Induction*

[%]


−9 −8 −7 −6 −50

20

40

60

80

100

log10(M)

Rela

tive Induction*

[%]


−9 −8 −7 −6 −50

20

40

60

80

100

log10(M)

Rela

tive Induction*

[%]


−9 −8 −7 −6 −5

20

40

60

80

100

log10(M)

Rela

tive Induction*

[%]


−9 −8 −7 −6 −50

20

40

60

80

100

log10(M)

Rela

tive Induction*

[%]TI−12ZV, run 28, RISE

−8 −7 −6 −50

20

40

60

80

100

log10(M)

Rela

tive Induction*

[%]


−8 −7 −6 −5

20

40

60

80

100

log10(M)

Rela

tive Induction*

[%]


−8 −7 −6 −50

20

40

60

80

100

log10(M)

Rela

tive Induction*

[%]





265

−8 −7 −6 −50

20

40

60

80

100

120

140

160

180

200

220

240

260

280

log10(M)

Rela

tive Induction [%

]

TI−CIT2TF, Citoxlab

run 11

run 17

run 21

Flutamide

−9 −8 −7 −6 −50

20

40

60

80

100

120

140

160

180

200

220

240

260

280

log10(M)

Rela

tive Induction [%

]

TI−ENV3EH, Envigo

run 6

run 9

run 10

Flutamide

−9 −8 −7 −6 −50

20

40

60

80

100

120

140

160

180

200

220

240

260

280

log10(M)

Rela

tive Induction [%

]

TI−12ZV, RISE

run 12

run 24

run 28

Flutamide

−8 −7 −6 −50

20

40

60

80

100

120

140

160

180

200

220

240

log10(M)

Rela

tive Induction [%

]

TI−BDS2MK, BDS

run 5

run 7

run 9

Flutamide


266

Citoxlab

Envigo

RISE

BDS

run11

run17

run21

run6

run9

run10

run12

run24

run28

run5

run7

run9

[µM]

[mg/ml]

COM

COM

COM

COM

COM

COM

COM

COM

COM

COM

COM

COM

1.54e-4

4.5e-8

105.5(15.1)106.9(5.4)

91.8(2.9)

4.62e-4

1.35e-7

94.3(4.9)

93.1(1.6)91.9(4.7)

5.13e-4

1.5e-7

112.3(6.4)

97.6(3)

100.6(3.7)

1.54e-3

4.5e-7

87.9(4.7)91.7(7.6)89.4(3.4)

88.5(23.2)

108.8(3.2)

92.3(7.1)87.4(5.4)

87.8(1.7)95.9(3.1)82.5(1.1)94.5(2.9)89.9(3.1)

4.62e-3

1.35e-6

81.1(11.2)

73.7(1.7)

79.5(3.9)

5.13e-3

1.5e-6

80.9(4.8)

74.8(7.3)

74.3(2.7)

88.7(5.3)

87.9(4.1)

78.7(6.4)

68.7(6)

76.5(5.6)

75.8(4)

1.54e-2

4.5e-6

60.1(6)

57.4(2.3)

56.6(3.5)

61.8(6.1)

72.3(2.9)

63.5(2)

53(3.7)

49.8(2.1)

51.9(6.3)

44.8(0.9)

54.5(1.6)

55.7(1.2)

4.62e-2

1.35e-5

26.2(2.3)

25.7(2.1)

23.6(1)

5.13e-2

1.5e-5

25.9(0.3)

21.7(1.7)

23.3(1.8)

33.4(1.9)

33.1(2.7)

26.3(4.8)

18.6(1.4)

24.1(2.3)

25.2(1.7)

1.54e-1

4.5e-5

10.6(1.5)

15.9(0.9)

6.5(0.8)

17.3(3.4)

10.4(0.4)

12(0.6)

8(1.3)

6.6(0.1)

6.1(0.8)

5.8(0.2)

7.8(0.5)

6.4(0.3)

4.62e-1

1.35e-4

1.7(0.5)

1.7(0.3)

2.2(0.2)

5.13e-1

1.5e-4

3.3(0.5)

1.5(0.2)

1.5(0.1)

2.8(0.6)

1.8(0.3)

3.7(0.5)

1.6(0.3)

1.7(0.7)

2.1(0.1)

1.54

4.5e-4

1.5(0.3)

1(0.1)

1.1(0.1)

1.1(0.6)

1.6(0.2)

1(0.2)

1.1(0.1)

1(0.1)

1.2(0.1)

5.13

1.5e-3

2.5(0.1)

1.7(0.3)

2.1(0.1)

2.7(0.6)

1.6(0.2)

2.1(0.1)

R2

0.36

0.34

0.31

0.08

0.38

0.73

0.67

0.48

0.38

0.49

0.41

0.39

log 1

0(PC80)[mg/ml]

-5.79

-6.05

-6.05

-5.62

-5.55

-5.88

-5.84

-6.05

-5.88

-6.17

-5.92

-5.96

log 1

0(IC50)[mg/ml]

-5.13

-5.27

-5.21

-5.14

-5.08

-5.16

-5.24

-5.31

-5.29

-5.34

-5.31

-5.22


267

Citoxlab

Envigo

RISE

BDS

[mg/ml]

run11

run17

run21

run6

run9

run10

run12

run24

run28

run5

run7

run9

4.5e-8

184.1(8.5)

300(14.4)

233.8(9.2)

1.35e-7

213.5(3.6)

235.1(10.4)

277.2(11.4)

1.5e-7

206.9(6.2)

243.7(23.3)

237.2(23.1)

4.5e-7

279(7.8)

233.4(7.4)245.4(11.7)

176.9(8.4)

289(32.4)

237.5(3.2)

208.1(6.6)

234.4(10.7)

271.8(2.6)

243.5(5)

207(4.1)

236.4(15.8)

1.35e-6

200.4(7.6)

234.4(12.9)

282(6.1)

1.5e-6

275.7(14.9)

234.4(5.4)251.9(6.1)

157.6(53.7)263.2(19.4)

244(18)

220.2(8.7)199.9(6.3)

234.7(16)

4.5e-6

284.6(5.2)

238.5(6.3)251.3(11.6)

186.1(5.2)

262.7(7.5)226.3(7.6)

205.4(9.2)

232.5(7.8)

283.8(7.1)

223.7(4.7)200.9(12.9)

236.7(10.4)

1.35e-5

197.6(12.1)

229.1(4.9)

270.1(7.7)

1.5e-5

271.7(13)

239.1(3.6)251.7(13.3)

210.7(15.2)267.1(22.2)

221.5(22.6)

213.7(3.9)

189(6.1)

228(0.5)

4.5e-5

270.9(25.1)

224.7(4.1)243.3(11.2)

200.5(15.6)258.2(16.9)

225.7(18.1)181.3(17.5)

221.1(9.9)

267.7(4)

207.3(3.2)

202(9.5)

214.4(6.4)

1.35e-4

164.8(6)

199.1(10.8)

231.2(14.6)

1.5e-4

248.4(11.8)

211.4(4.7)

223(10.3)

185.6(9.2)

232.2(21.3)210.7(7.4)

182.1(6.7)

164.8(8.9)

211.1(15)

4.5e-4

194.9(7.8)

151.1(4)

165.9(4.2)

134.4(8.2)

154.1(3.5)

162.6(2.5)

147.3(1.9)

133.8(10)

169.3(7.1)

1.5e-3

110.8(3.3)

83(2.3)

92.9(4.2)

95(1.7)

85.5(2.6)

100.2(5.6)



268

−9 −8 −7 −6 −50

20

40

60

80

100

120

140

160

180

200

220

240

260

280

log10(M)

Rela

tive Induction [%

]


Citoxlab

Envigo

RISE

BDS

Flutamide


269

D.21 Test item 21

−12 −11 −10 −9 −8 −7 −6 −50

20

40

60

80

100

120

140

log10(M)

Rela

tive Induction [%

]TI−24RY, run 5, RISE

−12 −11 −10 −9 −8 −7 −6 −50

20

40

60

80

100

120

log10(M)

Rela

tive Induction [%

]


−12 −11 −10 −9 −8 −7 −6 −5

20

40

60

80

100

120

140

log10(M)

Rela

tive Induction [%

]




−12 −11 −10 −9 −8 −7 −6 −50

20

40

60

80

100

120

140

log10(M)

Rela

tive Induction [%

]

TI−24RY, RISE

run 5

run 21

run 29

Flutamide



[µM] [mg/ml] PRE PRE PRE4.8e-7 1.5e-10 103.1(1.5) 102.7 (4.5) 105.4(2.4)4.8e-6 1.5e-9 102.9(5.3) 89.5 (5.1) 101.4(1.4)4.8e-5 1.5e-8 101.8(5.3) 91.7 (1.2) 98.1 (4.2)4.8e-4 1.5e-7 122.8(3.6) 102.3 (2.5) 105.5(4.6)4.8e-3 1.5e-6 130.6(8.8) 116.8(13.6) 133.6(5.8)4.8e-2 1.5e-5 141.7(1.4) 113.7 (1.4) 135.5(7.4)4.8e-1 1.5e-4 151.3(0.6) 119.2 (6.1) 135.8 (3)4.8 1.5e-3 141.5(2.7) 114.1 (3.9) 131 (4.9)

R2

log10(PC80) [mg/ml]log10(IC50) [mg/ml]


270

D.22 Test item 22

−9 −8 −7 −6 −50

20

40

60

80

100

120

140

160

180

200

220

240

260

280

300

log10(M)

Rela

tive Induction [%

]TI−33TH, run 16, RISE

−9 −8 −7 −6 −5

20

40

60

80

100

120

140

160

180

200

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Rela

tive Induction [%

]


−9 −8 −7 −6 −50

20

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log10(M)

Rela

tive Induction [%

]




−9 −8 −7

20

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100

120

log10(M)

Rela

tive In

du

cti

on

[%

]


−9 −8 −7

20

40

60

80

100

log10(M)

Rela

tive In

du

cti

on

[%

]


−9 −8 −7

20

40

60

80

100

log10(M)

Rela

tive In

du

cti

on

[%

]





−9 −8 −7 −6 −50

20

40

60

80

100

120

140

160

180

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240

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300

320

340

log10(M)

Rela

tive Induction [%

]

TI−33TH, RISE

run 16

run 25

run 31

Flutamide


271


[µM] [mg/ml] COM COM COM1.08e-4 4.5e-8 105.2(10.5) 96.4 (2.1) 93 (5.9)3.6e-4 1.5e-7 107.8(13.5) 88.9 (2.9) 96.7 (9.7)1.08e-3 4.5e-7 93.6 (1.9) 86.4 (5.1) 85.9 (7.6)3.6e-3 1.5e-6 80.8 (12.7) 67.8(6.5) 71.2(3.3)1.08e-2 4.5e-6 46.1 (5.9) 45.7(3.2) 49.8(2.1)3.6e-2 1.5e-5 30.4 (6.1) 22.5(1.1) 24.7(2.1)1.08e-1 4.5e-5 14.6 (3.1) 11.3(0.3) 15.6(0.4)3.6e-1 1.5e-4 8.9 (1.2) 8.2 (0.5) 11 (1.6)

R2 0.48 0.43 0.46log10(PC80) [mg/ml] -5.81 -6.12 -6.12log10(IC50) [mg/ml] -5.48 -5.45 -5.42


RISE[mg/ml] run 16 run 25 run 314.5e-8 277.2 (4.9) 207.9 (4) 333.6 (11.8)1.5e-7 286.2 (7.8) 208 (12.3) 335.1 (22)4.5e-7 290.9 (6.4) 214 (4.6) 358 (15.5)1.5e-6 285 (17.6) 205.5 (1.7) 326.1 (40.3)4.5e-6 277.8 (11.7) 209.3 (9.1) 338 (10)1.5e-5 286.4 (13.2) 204.9 (9) 324.5 (12.5)4.5e-5 248 (9.5) 195.9 (1.6) 316.3 (13.9)1.5e-4 200.1 (4.4) 154.1 (9.1) 247.7(14.8)



272

D.23 Test item 23

−8 −7 −6 −5

20

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100

120

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260

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340

360

380

400

log10(M)

Re

lative

In

du

ctio

n [

%]


−8 −7 −6 −5

20

40

60

80

100

120

140

160

180

200

220

240

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340

log10(M)

Re

lative

In

du

ctio

n [

%]


−8 −7 −6 −50

20406080

100120140160180200220240260280300320340360380400420440460480

log10(M)

Re

lative

In

du

ctio

n [

%]




−8 −7 −6 −5

20

40

60

80

100

120

140

log10(M)

Rela

tive In

du

cti

on

[%

]


−8 −7 −6 −5

20

40

60

80

100

120

140

log10(M)

Rela

tive In

du

cti

on

[%

]


−8 −7 −6 −5

20

40

60

80

100

120

140

log10(M)

Rela

tive In

du

cti

on

[%

]





−8 −7 −6 −50

20406080

100120140160180200220240260280300320340360380400420440460480

log10(M)

Rela

tive Induction [%

]

TI−27YC, RISE

run 13

run 25

run 31

Flutamide


273


[µM] [mg/ml] COM COM COM5.68e-3 1.5e-6 107.1(10.8) 101.9 (6.9) 105.2(4.2)1.89e-2 5e-6 111.6 (5.1) 117.7 (6.2) 124 (3.4)5.68e-2 1.5e-5 142.1(15.2) 132.8 (4.9) 140.5(7.8)1.89e-1 5e-5 140.8(10.7) 142.8 (8.1) 135 (1.2)5.68e-1 1.5e-4 122.3(15.4) 122 (10.9) 121.5(4.9)1.89 5e-4 70.5 (3.6) 73.5 (1.1) 71.9(0.6)5.68 1.5e-3 19.9 (1.2) 27 (2.8) 24 (1.5)18.92 5e-3 3.6 (0.8) 0.6 (0.3) 0.9 (0.6)



RISE[mg/ml] run 13 run 25 run 311.5e-6 256.7(14.2) 253.3(10.7) 344.1 (21.1)5e-6 294.2(10.5) 284.2 (8.2) 381.3 (11)1.5e-5 331.2(21.6) 326.8(13.5) 418 (18.6)5e-5 380.5(36.1) 336.8(13.3) 494.4 (2.3)1.5e-4 379.3(16.9) 348.6 (9.3) 456.7 (9.9)5e-4 329.9(23.1) 315.1 (6.5) 426.5 (10)1.5e-3 234.6(44.6) 206 (9.7) 260.8 (2)5e-3 57.6 (7.5) 49.5 (4.1) 50.4 (5.3)



274

D.24 Test item 24

−8 −7 −6 −50

20

40

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120

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180

200

220

240

log10(M)

Re

lative

In

du

ctio

n [

%]


−8 −7 −6 −5

20

40

60

80

100

120

140

160

180

200

220

log10(M)

Re

lative

In

du

ctio

n [

%]


−8 −7 −6 −50

20

40

60

80

100

120

140

160

180

200

220

240

260

280

300

320

340

log10(M)

Re

lative

In

du

ctio

n [

%]




−8 −7 −6 −50

20

40

60

80

100

log10(M)

Rela

tive In

du

cti

on

[%

]


−8 −7 −6 −5

20

40

60

80

100

log10(M)

Rela

tive In

du

cti

on

[%

]


−8 −7 −6 −5

20

40

60

80

100

log10(M)

Rela

tive In

du

cti

on

[%

]





−8 −7 −6 −50

20

40

60

80

100

120

140

160

180

200

220

240

260

280

300

320

log10(M)

Rela

tive Induction [%

]

TI−15SB, RISE

run 12

run 22

run 34

Flutamide


275


[µM] [mg/ml] COM COM COM4.6e-3 1.5e-6 93.8 (6.7) 91.4 (7.9) 94 (7.9)1.53e-2 5e-6 91.1 (3.4) 93.8 (4.2) 94.9 (3.3)4.6e-2 1.5e-5 85 (5) 88.1 (5.5) 92.8 (4.9)1.53e-1 5e-5 77.5(3.5) 77.1(0.8) 71.8(5.7)4.6e-1 1.5e-4 60.8 (5) 55.7(2.2) 54.9(5.6)1.53 5e-4 26.9(1.1) 24 (1.6) 21 (0.7)4.6 1.5e-3 6.9 (1.7) 7.7 (0.4) 6.8 (1.6)15.32 5e-3 0.7 (0.7) 1.6 (0.7) 1 (0.4)



RISE[mg/ml] run 12 run 22 run 341.5e-6 216.2 (5.2) 212.9 (10.8) 327 (12)5e-6 210.9 (13) 206.6 (16.5) 319.4 (8.1)1.5e-5 227.4 (11.6) 204.7 (3.9) 319.2 (15.8)5e-5 215.5 (2.1) 202.3 (7.7) 330.4 (16.3)1.5e-4 211.8 (5.6) 203.5 (2.1) 333.9 (4.6)5e-4 200.2 (13.4) 202.3 (8.6) 334.5 (13.7)1.5e-3 192.2 (5.4) 193.4 (12.6) 305 (11)5e-3 155.9 (9.9) 162.1 (6.2) 256.7(16.2)



276

D.25 Test item 25

−10 −9 −8 −7 −6 −5 −40

20

40

60

80

100

120

140

160

180

200

220

log10(M)

Re

lative

In

du

ctio

n [

%]


−10 −9 −8 −7 −6 −5 −40

20

40

60

80

100

120

140

160

180

200

220

log10(M)

Rela

tive Induction [%

]


−11 −10 −9 −8 −7 −6 −5

20

40

60

80

100

120

140

160

180

200

220

240

260

280

300

320

340

360

380

log10(M)

Re

lative

In

du

ctio

n [

%]




−11 −10 −9 −8 −7 −6 −5 −40

20

40

60

80

100

120

140

160

180

200

220

240

260

280

300

320

340

log10(M)

Rela

tive Induction [%

]

TI−37VK, RISE

run 11

run 21

run 32

Flutamide



[µM] [mg/ml] PRE PRE PRE1.82e-6 5e-10 108.6 (15)1.82e-5 5e-9 101.9 (2.1) 98.7 (4) 109 (3.8)1.82e-4 5e-8 133 (9.1) 120.4 (6.1) 167.7 (5.7)1.82e-3 5e-7 205.4 (4.2) 186.4(13.9) 280.6(26.7)1.82e-2 5e-6 217 (18.6) 211.5(10.6) 329.9 (9.5)1.82e-1 5e-5 212.5(15.8) 216.6 (6.5) 344.7(31.8)1.82 5e-4 218.2 (5.1) 226.2(16.1) 341.3(21.8)18.22 5e-3 197.8(19.5) 199.6 (1.8) 313.8 (3.7)182.22 5e-2 91.2 (3.8) cyt/excl

R2



277

D.26 Test item 26

−8 −7 −6 −50

20

40

60

80

100

120

140

160

180

200

220

240

log10(M)

Rela

tive Induction [%

]TI−13GZ, run 12, RISE

−8 −7 −6 −5

20

40

60

80

100

120

140

160

180

200

220

240

log10(M)

Rela

tive Induction [%

]


−8 −7 −6 −50

20

40

60

80

100

120

140

160

180

200

220

240

260

280

log10(M)

Rela

tive Induction [%

]




−8 −7 −6

20

40

60

80

100

log10(M)

Rela

tive In

du

cti

on

[%

]


−8 −7 −6

20

40

60

80

100

log10(M)

Rela

tive In

du

cti

on

[%

]


−8 −7 −6

20

40

60

80

100

log10(M)

Rela

tive In

du

cti

on

[%

]





−8 −7 −6 −50

20

40

60

80

100

120

140

160

180

200

220

240

260

log10(M)

Rela

tive Induction [%

]

TI−13GZ, RISE

run 12

run 24

run 28

Flutamide


278


[µM] [mg/ml] COM COM COM1.27e-3 4.5e-7 102.9(7.8) 93.1 (4.4) 91.5 (5.9)4.23e-3 1.5e-6 101.6(1.7) 98.7 (2.1) 87.6 (3.5)1.27e-2 4.5e-6 106.5(6.1) 99.7 (6.3) 88.2 (0.9)4.23e-2 1.5e-5 95.8 (7.4) 90.8 (1.5) 80.6 (1.7)1.27e-1 4.5e-5 82.2 (6.2) 76.2(1.5) 71.8(4.6)4.23e-1 1.5e-4 55.9(4.4) 48.3(2.2) 47.1(4.2)1.27 4.5e-4 27 (1.2) 20.2(1.3) 18.1(3.1)4.23 1.5e-3 4.2 (0.6) 3.7 (0.1) 4.3 (0.3)



RISE[mg/ml] run 12 run 24 run 284.5e-7 230.7(11.5) 234.9 (6.3) 265.1 (6.8)1.5e-6 227.9 (9.9) 237 (10.6) 269.9 (5.3)4.5e-6 234.2 (4.8) 239.1 (7.6) 266.1 (7.3)1.5e-5 229.3(12.2) 223.1 (3.9) 260.2 (10)4.5e-5 240.5(11.9) 224.6 (8.7) 274.2(16.9)1.5e-4 238.7(10.9) 227.9(16.2) 269.4 (16)4.5e-4 242.8 (9.2) 226.9 (7.2) 253.6(13.2)1.5e-3 225.2 (3.2) 206.9 (3.7) 220.1 (5.9)



279

D.27 Test item 27

−11 −10 −9 −8 −7 −6 −50

20

40

60

80

100

log10(M)

Re

lative

In

du

ctio

n [

%]


−11 −10 −9 −8 −7 −6 −50

20

40

60

80

100

log10(M)

Re

lative

In

du

ctio

n [

%]


−11 −10 −9 −8 −7 −6 −5

20

40

60

80

100

120

log10(M)

Re

lative

In

du

ctio

n [

%]




−11 −10 −9 −8 −7 −6 −50

20

40

60

80

100

log10(M)

Rela

tive Induction [%

]

TI−31RX, RISE

run 9

run 21

run 32

Flutamide



[µM] [mg/ml] PRE PRE PRE4.68e-6 1.5e-9 91.3 (4.3) 95.7 (4.4) 108.6 (2.4)4.68e-5 1.5e-8 99.5 (2.7) 98.3 (3.8) 113.8 (3.3)4.68e-4 1.5e-7 99.4 (3) 105.3(5.3) 111.7 (7.9)4.68e-3 1.5e-6 104.6(3.7) 100.2(4.9) 109.2 (8.2)4.68e-2 1.5e-5 99.4 (8.3) 101.6(5.4) 100 (6.9)4.68e-1 1.5e-4 101.3(7.4) 100.9(2.7) 101.3 (3.9)4.68 1.5e-3 98.8 (3) 101.8 (1) 109.7(11.2)46.83 1.5e-2 97.1 (4.1) 97.6 (4.4) 104.8 (3.4)

R2



280

D.28 Test item 28

−13 −12 −11 −10 −9 −8 −7 −6 −50

20

40

60

80

100

log10(M)

Rela

tive Induction [%

]TI−29DC, run 11, RISE

−13 −12 −11 −10 −9 −8 −7 −6 −50

20

40

60

80

100

log10(M)

Rela

tive Induction [%

]


−13 −12 −11 −10 −9 −8 −7 −6 −50

20

40

60

80

100

log10(M)

Rela

tive Induction [%

]




−13 −12 −11 −10 −9 −8 −7 −6 −50

20

40

60

80

100

log10(M)

Rela

tive Induction [%

]

TI−29DC, RISE

run 11

run 15

run 29

Flutamide



[µM] [mg/ml] PRE PRE PRE5.87e-8 1.5e-11 101.2 (1) 96.6 (2.6) 101.4 (9)5.87e-7 1.5e-10 102.2(2.5) 92.4 (5.7) 107.8(3.6)5.87e-6 1.5e-9 101 (1.3) 80.8 (6.8) 107.4(6.6)5.87e-5 1.5e-8 98.7 (0.7) 87.2 (7.7) 108.7(5.1)5.87e-4 1.5e-7 98.5 (0.6) 100.4 (1.7) 104.7(1.1)5.87e-3 1.5e-6 101.3 (5) 101.7(13.5) 99.3 (5.6)5.87e-2 1.5e-5 99.4 (7) 95.3 (8.7) cyt/excl5.87e-1 1.5e-4 100.5(3.8) 97.7 (10.3) 111.6(3.2)

R2



281

D.29 Test item 29

−10 −9 −8 −7 −6 −5 −40

20

40

60

80

100

120

140

160

180

200

log10(M)

Re

lative

In

du

ctio

n [

%]


−10 −9 −8 −7 −6 −5 −40

20

40

60

80

100

120

140

160

180

200

log10(M)

Rela

tive Induction [%

]


−11 −10 −9 −8 −7 −6 −50

20

40

60

80

100

120

140

160

180

200

log10(M)

Re

lative

In

du

ctio

n [

%]




−11 −10 −9 −8 −7 −6 −5 −40

20

40

60

80

100

120

140

160

180

200

log10(M)

Rela

tive Induction [%

]

TI−34VE, RISE

run 11

run 15

run 21

Flutamide



[µM] [mg/ml] PRE PRE PRE1.76e-6 5e-10 108.2 (8.4)1.76e-5 5e-9 102.3 (5.6) 99.5 (4.4) 106.6(11.9)1.76e-4 5e-8 125.5 (7) 129.8(5.4) 130.4(17.1)1.76e-3 5e-7 164.6 (8.6) 177.8 (13) 169.5 (9.9)1.76e-2 5e-6 177.7 (7) 201.8(5.4) 186.2 (8.6)1.76e-1 5e-5 185.5 (19.6) 192.9(3.8) 188.4 (9.7)1.76 5e-4 182.4 (9.8) 190.5 (4) 193.5(13.5)17.58 5e-3 150.7 (9) 171.9(8.5) 155 (8.8)175.81 5e-2 29 (1.9) cyt/exclinterp value (x,y) (2.5e-2,65.6)

R2

log10(PC80) [mg/ml] -1.61log10(IC50) [mg/ml] -2.07


282

D.30 Test item 30

−11 −10 −9 −8 −7 −6 −50

20

40

60

80

100

120

140

160

180

200

220

log10(M)

Rela

tive Induction [%

]TI−07FK, run 20, RISE

−11 −10 −9 −8 −7 −6 −5

20

40

60

80

100

120

140

160

180

200

220

240

log10(M)

Rela

tive Induction [%

]


−11 −10 −9 −8 −7 −6 −5

20

40

60

80

100

120

140

160

180

200

220

240

260

log10(M)

Rela

tive Induction [%

]




−11 −10 −9 −80

20

40

60

80

100

log10(M)

Re

lati

ve

In

du

cti

on

[%

]

TI−07FK, run 20, RISE, int=88.99

−11 −10 −9

40

60

80

100

log10(M)

Rela

tive In

du

cti

on

[%

]


−11 −10 −9

40

60

80

100

log10(M)

Rela

tive In

du

cti

on

[%

]





−11 −10 −9 −8 −7 −6 −50

20

40

60

80

100

120

140

160

180

200

220

240

260

log10(M)

Rela

tive Induction [%

]

TI−07FK, RISE

run 20

run 27

run 30

Flutamide


283


[µM] [mg/ml] COM COM COM1.19e-6 1.5e-9 95.8 (1.7) 94.2 (2.7)3.58e-6 4.5e-9 96.5 (6.5)3.98e-6 5e-9 93.5 (5.2) 91.9 (6.7)1.19e-5 1.5e-8 100.7 (4.6) 92.7 (1.7) 94 (4.3)3.58e-5 4.5e-8 94.3 (5.1)3.98e-5 5e-8 94.1 (7.4) 93.1 (0.8)1.19e-4 1.5e-7 103.6 (5.9) 91.8 (3.9) 92.9 (4.3)3.58e-4 4.5e-7 102.5 (2.7)3.98e-4 5e-7 95.4 (7.7) 95.7 (3.9)1.19e-3 1.5e-6 107.6 (3.4) 82.4 (2.9) 85.8 (4.5)3.58e-3 4.5e-6 57.2 (4.6)3.98e-3 5e-6 39 (3.3) 37.5 (4.1)1.19e-2 1.5e-5 cyt/exclinterp value (x,y) (2.25e-6,89) (2.5e-6,64) (2.5e-6,65.3)



RISE[mg/ml] run 20 run 27 run 301.5e-9 231.1(17.7) 260.3 (4.2)4.5e-9 221.2 (4.4)5e-9 234.8 (6.7) 265.6 (8.4)1.5e-8 219.8 (7.3) 238.1 (9.6) 267.5 (11.5)4.5e-8 209.5 (5.2)5e-8 228.8 (9.8) 258.6 (5.2)1.5e-7 208.2 (5) 224 (0.3) 248.8 (10.7)4.5e-7 219.3 (3.1)5e-7 221.2 (8) 255.9 (5.4)1.5e-6 222.9 (3.2) 193.5 (3.1) 228.8 (2.1)4.5e-6 136.5(5.1)5e-6 96.3 (7.2) 110.2 (7.4)1.5e-5 cyt/excl



284

D.31 Test item 31

−8 −7 −6 −50

20

40

60

80

100

120

140

160

180

200

220

240

260

log10(M)

Rela

tive Induction [%

]TI−01JA, run 10, RISE

−8 −7 −6 −5

20

40

60

80

100

120

140

160

180

200

220

240

260

280

log10(M)

Rela

tive Induction [%

]


−8 −7 −6 −5

20

40

60

80

100

120

140

160

180

200

220

240

260

280

300

320

340

360

log10(M)

Rela

tive Induction [%

]




−8 −7 −6 −50

20

40

60

80

100

log10(M)

Re

lati

ve

In

du

cti

on

[%

]


−8 −7 −6

20

40

60

80

100

log10(M)

Rela

tive In

du

cti

on

[%

]


−8 −7 −6

20

40

60

80

100

log10(M)

Rela

tive In

du

cti

on

[%

]





−8 −7 −6 −50

20

40

60

80

100

120

140

160

180

200

220

240

260

280

300

320

340

log10(M)

Rela

tive Induction [%

]

TI−01JA, RISE

run 10

run 30

run 33

Flutamide


285


[µM] [mg/ml] COM COM COM1.68e-3 4.5e-7 98 (5.5) 97.4 (2.8)5.03e-3 1.35e-6 92.4 (2.8)5.59e-3 1.5e-6 102.1(5.3) 99.1 (3.9)1.68e-2 4.5e-6 90.3 (2.2) 101 (4) 97.5 (0.4)5.03e-2 1.35e-5 89.1 (7)5.59e-2 1.5e-5 94.1 (4.5) 88.8 (3)1.68e-1 4.5e-5 83.4 (6.5) 86.8 (1.3) 89.2 (6)5.03e-1 1.35e-4 68.3(3.2)5.59e-1 1.5e-4 70.9(1.7) 72.8(7.7)1.68 4.5e-4 38.6(0.9) 43.4(1.4) 41.5 (3)5.03 1.35e-3 14.3(1.1)5.59 1.5e-3 14.3(0.9) 15.1 (2)16.77 4.5e-3 cyt/excl



RISE[mg/ml] run 10 run 30 run 334.5e-7 275.2 (3.3) 346.6(17.6)1.35e-6 244.9 (5.1)1.5e-6 276.6 (5.4) 328.9(12.4)4.5e-6 245.1 (5.5) 281.7(14.3) 332.2(16.1)1.35e-5 241.1 (5.5)1.5e-5 276.2 (8.5) 335.2(13.8)4.5e-5 249.6 (2.9) 274.1 (6) 320.5(11.2)1.35e-4 241.3 (9.5)1.5e-4 273 (9.6) 337 (4.8)4.5e-4 242 (11.2) 269.1 (8.5) 333.7 (13)1.35e-3 238.8(24.4)1.5e-3 250.7(10.2) 319 (12.4)4.5e-3 cyt/excl



286

D.32 Test item 32

−11 −10 −9 −8 −7 −6 −50

20

40

60

80

100

log10(M)

Re

lative

In

du

ctio

n [

%]


−11 −10 −9 −8 −7 −6 −50

20

40

60

80

100

log10(M)

Rela

tive Induction [%

]


−12 −11 −10 −9 −8 −7 −6 −5

20

40

60

80

100

log10(M)

Rela

tive Induction [%

]




−12 −11 −10 −9 −8 −7 −6 −50

20

40

60

80

100

log10(M)

Rela

tive Induction [%

]

TI−19TM, RISE

run 5

run 21

run 32

Flutamide



[µM] [mg/ml] PRE PRE PRE6.44e-7 5e-10 102.1 (2)6.44e-6 5e-9 103 (9.5) 101.6(0.4) 107 (5.3)6.44e-5 5e-8 102.8 (2.3) 98.4 (3.8) 104.6(3.5)6.44e-4 5e-7 109.8 (6) 96.2 (6) 101 (3.8)6.44e-3 5e-6 106.1 (4.8) 98.2 (2.8) 104.9(6.7)6.44e-2 5e-5 113.2 (3.7) 104.7(2.5) 108.8(8.4)6.44e-1 5e-4 109.1 (10.8) 95.4 (3.8) 108.4(8.4)6.44 5e-3 94.2 (5.3) 102.7(8.7) 107.8 (8)64.36 5e-2 13.9 (2) cyt/exclinterp value (x,y) (2.5e-2,38.1)

R2

log10(PC80) [mg/ml] -2log10(IC50) [mg/ml] -2.16


287

D.33 Test item 33

−11 −10 −9 −8 −7 −6 −5

20

40

60

80

100

120

log10(M)

Rela

tive Induction [%

]TI−05BR, run 1, RISE

−11 −10 −9 −8 −7 −6 −50

20

40

60

80

100

120

log10(M)

Rela

tive Induction [%

]


−11 −10 −9 −8 −7 −6 −50

20

40

60

80

100

120

log10(M)

Rela

tive Induction [%

]




−11 −10 −9 −8 −7 −6 −50

20

40

60

80

100

120

log10(M)

Rela

tive Induction [%

]

TI−05BR, RISE

run 1

run 15

run 26

Flutamide



[µM] [mg/ml] PRE PRE PRE1.33e-6 5e-10 109.8(7.2) 102.3 (5.3) 111.9 (5.3)1.33e-5 5e-9 101.7(2.1) 97.6 (10.2) 110.1 (7.1)1.33e-4 5e-8 100.7(4.5) 110.1 (17) 112 (5.2)1.33e-3 5e-7 101.3(8.3) 97.3 (9.5) 115 (3.5)1.33e-2 5e-6 104 (2.7) 104.9 (9.5) 130.7 (6.9)1.33e-1 5e-5 105.6(1.3) 94.6 (3) 111.8 (7.6)1.33 5e-4 109.9(3.9) 108.2 (5.7) 122.6(11.1)13.3 5e-3 125.7(2.5) 117 (4.5) cyt/excl

R2



288

D.34 Test item 34

−8 −7 −6 −50

20

40

60

80

100

120

140

160

180

200

220

240

260

280

log10(M)

Rela

tive Induction [%

]TI−36XY, run 16, RISE

−8 −7 −6 −50

20

40

60

80

100

120

140

160

180

200

220

log10(M)

Rela

tive Induction [%

]


−8 −7 −6 −50

20

40

60

80

100

120

140

160

180

200

220

240

260

280

log10(M)

Rela

tive Induction [%

]




−8 −7 −6 −5

20

40

60

80

100

120

log10(M)

Rela

tive In

du

cti

on

[%

]

TI−36XY, run 16, RISE, int=73.14

−8 −7 −6 −520

40

60

80

100

log10(M)

Rela

tive In

du

cti

on

[%

]


−8 −7 −6 −5

40

60

80

100

log10(M)

Rela

tive In

du

cti

on

[%

]

TI−36XY, run 31, RISE, int=79.14




−8 −7 −6 −50

20

40

60

80

100

120

140

160

180

200

220

240

260

280

log10(M)

Rela

tive Induction [%

]

TI−36XY, RISE

run 16

run 20

run 31

Flutamide


289


[µM] [mg/ml] COM COM COM4.41e-3 1.5e-6 108.5 (15.7) 98.7 (7.4) 94.7 (5.1)1.47e-2 5e-6 103.1 (14.7) 93.1 (0.9) 105.9 (3.9)4.41e-2 1.5e-5 100.2 (2.6) 89.3 (3.8) 111.5 (4.2)1.47e-1 5e-5 97.5 (4.8) 80.6 (9.2) 105.7 (2.1)4.41e-1 1.5e-4 90.5 (8.9) 77.7(1.4) 104.6 (3.1)1.47 5e-4 99.7 (7.7) 85.9 (4.4) 102.4 (10.6)4.41 1.5e-3 86.8 (6.2) 79 (7.1) 96 (4.5)14.68 5e-3 54.6 (2.8) 40.9(3.5) 56.2 (5.8)interp value (x,y) (2.5e-3,73.1) (2.5e-3,79.1)

R2 0.85 0.73 0.62log10(PC80) [mg/ml] -2.7 na -2.53log10(IC50) [mg/ml] na na na


RISE[mg/ml] run 16 run 20 run 311.5e-6 284.4 (3.7) 205.5 (2.8) 274.6 (11.2)5e-6 257.9 (14.7) 214.8 (9.7) 277.8 (5.9)1.5e-5 259.2 (8.6) 203.1 (5.4) 265.8 (10.6)5e-5 219.2(16.3) 181.5 (6.1) 255.3 (5.4)1.5e-4 197.3 (18) 155.6 (5) 225 (1.5)5e-4 163 (20.5) 126.1(1.8) 169.9 (3.9)1.5e-3 121.8(11.4) 91.6 (3.4) 129.6 (6.3)5e-3 24.1 (3.2) 43.7 (4.2) 64.6 (4.3)



290

D.35 Test item 35

−11 −10 −9 −8 −7 −6 −50

20

40

60

80

100

log10(M)

Rela

tive Induction [%

]TI−23QM, run 9, RISE

−12 −11 −10 −9 −8 −7 −6 −50

20

40

60

80

log10(M)

Re

lative

In

du

ctio

n [

%]


−12 −11 −10 −9 −8 −7 −6 −5

20

40

60

80

100

120

log10(M)

Rela

tive Induction [%

]




−12 −11 −10 −9 −8 −7 −6 −50

20

40

60

80

100

log10(M)

Rela

tive Induction [%

]

TI−23QM, RISE

run 9

run 21

run 29

Flutamide



[µM] [mg/ml] PRE PRE PRE1.08e-7 5e-11 95.9(1.3) 105.1(6.8)1.08e-6 5e-10 104.9(7.1) 94.7 (3) 111.3(9.5)1.08e-5 5e-9 101.5(5.5) 90.1(4.4) 109.4(9.2)1.08e-4 5e-8 101.5(1.6) 86.1(6.8) 111.6(8.8)1.08e-3 5e-7 99.6 (7.6) 92.1(1.9) 103.5(3.4)1.08e-2 5e-6 104.6(4.3) 88.6(6.3) 109.3(9.8)1.08e-1 5e-5 97.4 (9.6) 93.1(2.6) 102.9(6.6)1.08 5e-4 90.3 (2.7) 86.4(6.9) 95.8 (3.2)10.83 5e-3 cyt/excl

R2



291

D.36 Test item 36

−9 −8 −7 −6 −50

20

40

60

80

100

120

140

160

180

200

220

log10(M)

Rela

tive Induction [%

]TI−10JQ, run 12, RISE

−9 −8 −7 −6 −5

20

40

60

80

100

120

140

160

180

200

220

240

log10(M)

Rela

tive Induction [%

]


−9 −8 −7 −6 −50

20

40

60

80

100

120

140

160

180

200

220

240

260

280

log10(M)

Rela

tive Induction [%

]




−9 −8 −7 −6

20

40

60

80

100

log10(M)

Rela

tive In

du

cti

on

[%

]


−9 −8 −7

20

40

60

80

100

log10(M)

Rela

tive In

du

cti

on

[%

]


−9 −8 −7

20

40

60

80

100

log10(M)

Rela

tive In

du

cti

on

[%

]





−9 −8 −7 −6 −50

20

40

60

80

100

120

140

160

180

200

220

240

260

log10(M)

Rela

tive Induction [%

]

TI−10JQ, RISE

run 12

run 24

run 28

Flutamide


292


[µM] [mg/ml] COM COM COM1.43e-4 4.5e-8 95.5 (9.5) 100.8(5.2)4.29e-4 1.35e-7 94.7 (6.1)4.77e-4 1.5e-7 87.6 (3.9) 94.8 (3.4)1.43e-3 4.5e-7 85.9 (1.2) 81.4 (5.7) 81.8 (4.3)4.29e-3 1.35e-6 72.1 (7)4.77e-3 1.5e-6 64.4(4.4) 65.5(3.6)1.43e-2 4.5e-6 40.3 (1) 37 (2.8) 45 (3)4.29e-2 1.35e-5 21 (2.3)4.77e-2 1.5e-5 17.3(0.8) 20.4(1.5)1.43e-1 4.5e-5 10.2(1.1) 9.2 (0.4) 10.7(1.7)4.29e-1 1.35e-4 7.1 (0.7)4.77e-1 1.5e-4 7 (0.5) 7.7 (1.3)1.43 4.5e-4 10.7(0.7)



RISE[mg/ml] run 12 run 24 run 284.5e-8 252.3 (6.4) 265.4(13.3)1.35e-7 213.8 (6.9)1.5e-7 239.6 (7.6) 275.4 (3.9)4.5e-7 226.8 (12.9) 242.1 (13.4) 273 (7)1.35e-6 221.1 (11)1.5e-6 237.8 (4.5) 270 (9.5)4.5e-6 218.9 (12.3) 229.3 (6.3) 273 (8.6)1.35e-5 216.5 (2.6)1.5e-5 236.8 (8.2) 269.1 (4)4.5e-5 204.2 (16.6) 212.5 (8.4) 244.1 (9)1.35e-4 167.9 (3)1.5e-4 172.7 (3.2) 188 (8.2)4.5e-4 107.2 (4.7)



293

D.37 Test item 37

−8 −7 −6 −50

20

40

60

80

100

120

140

160

180

200

220

240

260

280

log10(M)

Re

lative

In

du

ctio

n [

%]


−8 −7 −6 −5

20

40

60

80

100

120

140

160

180

200

220

240

260

log10(M)

Re

lative

In

du

ctio

n [

%]


−8 −7 −6 −5

20

40

60

80

100

120

140

160

180

200

220

240

260

280

log10(M)

Re

lative

In

du

ctio

n [

%]




−7 −6 −5

20

40

60

80

100

log10(M)

Rela

tive In

du

cti

on

[%

]


−7 −6 −5

20

40

60

80

100

log10(M)

Rela

tive In

du

cti

on

[%

]


−7 −6 −5

20

40

60

80

100

log10(M)

Rela

tive In

du

cti

on

[%

]





−8 −7 −6 −50

20

40

60

80

100

120

140

160

180

200

220

240

260

280

log10(M)

Rela

tive Induction [%

]

TI−04NQ, RISE

run 10

run 24

run 30

Flutamide


294


[µM] [mg/ml] COM COM COM1.81e-2 4.5e-6 98.9 (6.1) 94.3 (3.8) 91.4 (2.5)6.02e-2 1.5e-5 95.7 (0.6) 93.7 (7) 89.5 (2.2)1.81e-1 4.5e-5 94.4 (4.3) 88.4 (2.7) 82.9 (1.6)6.02e-1 1.5e-4 72.5(6.2) 74.6(1.7) 64 (0.9)1.81 4.5e-4 50.3(6.3) 51.2(2.6) 40.9(2.5)6.02 1.5e-3 18.1(1.9) 19.3(3.1) 15.7(0.8)18.07 4.5e-3 5.9 (0.5) 5.2 (0.4) 4.6 (0.9)60.22 1.5e-2 2.3 (0.3) 1.7 (0.3) 1.3 (0.1)



RISE[mg/ml] run 10 run 24 run 304.5e-6 260 (10.2) 246.9 (8.6) 259.7 (12.9)1.5e-5 260.2 (6.5) 242.4 (4.2) 267.5 (13.7)4.5e-5 266.1 (4.7) 250.1 (1) 262.3 (16.7)1.5e-4 279.3(15.8) 253 (7.4) 272.1 (5.7)4.5e-4 279 (3.2) 251.7 (5.3) 271.9 (4.2)1.5e-3 287 (6.7) 260.4 (9.7) 285.3 (9.5)4.5e-3 257 (17) 248.3 (15.5) 240.7 (11)1.5e-2 132 (3.1) 122.6 (7) 122.6 (3.2)



295

D.38 Test item 38

−11 −10 −9 −8 −7 −6 −50

20

40

60

80

100

120

140

160

log10(M)

Rela

tive Induction [%

]TI−25RV, run 7, RISE

−12 −11 −10 −9 −8 −7 −6 −50

20

40

60

80

100

120

140

160

180

200

220

log10(M)

Rela

tive Induction [%

]


−12 −11 −10 −9 −8 −7 −6 −5

20

40

60

80

100

120

140

160

180

200

log10(M)

Rela

tive Induction [%

]




−12 −11 −10 −9 −8 −7 −6 −50

20

40

60

80

100

120

140

160

180

200

log10(M)

Rela

tive Induction [%

]

TI−25RV, RISE

run 7

run 21

run 26

Flutamide



[µM] [mg/ml] PRE PRE PRE4.96e-7 1.5e-10 104.1 (0.5) 101.4(2.4)4.96e-6 1.5e-9 85.5 (3.2) 102.1 (3.8) 101.6(2.7)4.96e-5 1.5e-8 95.1 (13.7) 109.1 (6) 109.7 (5)4.96e-4 1.5e-7 109.1(10.9) 119.4 (2.5) 126.7(4.9)4.96e-3 1.5e-6 140.8 (7.1) 177.6(10.2) 170 (5.1)4.96e-2 1.5e-5 158.6 (4) 184 (12.4) 191.5(6.2)4.96e-1 1.5e-4 162.3(11.4) 189.6 (4.3) 185.8(4.4)4.96 1.5e-3 157.6 (5.8) 207.2(12.5) 195.3(7.7)49.59 1.5e-2 cyt/excl

R2



296

D.39 Test item 39

−8 −7 −6 −50

20

40

60

80

100

120

140

160

180

200

220

log10(M)

Re

lative

In

du

ctio

n [

%]


−8 −7 −6 −5

20

40

60

80

100

120

140

160

180

200

220

240

log10(M)

Re

lative

In

du

ctio

n [

%]


−8 −7 −6 −50

20

40

60

80

100

120

140

160

180

200

220

240

260

280

300

320

340

360

log10(M)

Re

lative

In

du

ctio

n [

%]




−7 −6 −5

20

40

60

80

100

log10(M)

Rela

tive In

du

cti

on

[%

]


−7 −6 −5

20

40

60

80

100

log10(M)

Rela

tive In

du

cti

on

[%

]


−7 −6 −5

20

40

60

80

100

log10(M)

Rela

tive In

du

cti

on

[%

]





−8 −7 −6 −50

20

40

60

80

100

120

140

160

180

200

220

240

260

280

300

320

340

log10(M)

Rela

tive Induction [%

]

TI−16UA, RISE

run 20

run 27

run 34

Flutamide


297


[µM] [mg/ml] COM COM COM3e-2 4.5e-6 89.8 (4) 96.2 (1.9) 101.3(6.5)9.99e-2 1.5e-5 88 (1) 89 (7.4) 89.6 (9.3)3e-1 4.5e-5 78.2(1.3) 81.3 (1.2) 73.9(1.7)9.99e-1 1.5e-4 63.3(3.8) 59.2(3.3) 54.5(8.2)3 4.5e-4 44.4(2.8) 39.1(1.9) 44.2(6.2)9.99 1.5e-3 23.4(1.9) 22.5(1.6) 24.6(5.1)29.96 4.5e-3 12.8(2.8) 11.8(1.8) 18.6(6.2)99.87 1.5e-2 6.8 (1.6) 7.2 (2.4) 17.3(1.3)



RISE[mg/ml] run 20 run 27 run 344.5e-6 222.2(4.6) 248.7 (8.5) 352.6 (9.8)1.5e-5 220.9(5.5) 244.2 (9.2) 353.3(12.9)4.5e-5 218.5 (8) 239.2(12.5) 355.3 (7.4)1.5e-4 213 (6.8) 220.8 (11) 356.7(16.4)4.5e-4 215 (5.2) 228.4(11.9) 350.2(11.6)1.5e-3 207.8 (11) 223.9 (9.1) 338.8 (2)4.5e-3 203.9(4.9) 222.6 (4.5) 350.9 (3.9)1.5e-2 202.4(3.9) 215.6 (3.4) 309 (8.9)



298

D.40 Test item 40

−8 −7 −6 −50

20

40

60

80

100

120

140

160

180

200

220

240

260

280

300

log10(M)

Re

lative

In

du

ctio

n [

%]


−8 −7 −6 −5

20

40

60

80

100

120

140

160

180

200

220

240

260

280

log10(M)

Re

lative

In

du

ctio

n [

%]


−8 −7 −6 −50

20

40

60

80

100

120

140

160

180

200

220

240

260

280

300

320

log10(M)

Re

lative

In

du

ctio

n [

%]




−7 −6 −5

20

40

60

80

100

log10(M)

Rela

tive In

du

cti

on

[%

]


−7 −6 −5

20

40

60

80

100

log10(M)

Rela

tive In

du

cti

on

[%

]


−7 −6 −5

20

40

60

80

100

120

log10(M)

Rela

tive In

du

cti

on

[%

]





−8 −7 −6 −50

20

40

60

80

100

120

140

160

180

200

220

240

260

280

300

log10(M)

Rela

tive Induction [%

]

TI−08WJ, RISE

run 10

run 27

run 28

Flutamide


299


[µM] [mg/ml] COM COM COM1.3e-2 4.5e-6 98.7 (10.7) 98.5 (6.5) 92.7 (7)4.33e-2 1.5e-5 98 (4.2) 101.5(3.1) 89.1 (3.6)1.3e-1 4.5e-5 86.3 (3.6) 83.1 (0.9) 81.5 (5.6)4.33e-1 1.5e-4 53 (0.8) 56.5(2.9) 52.1(3.7)1.3 4.5e-4 25.1 (1.2) 23.7(1.3) 21.3(1.1)4.33 1.5e-3 8.8 (0.8) 9.2 (1.1) 8.4 (0.9)12.99 4.5e-3 4.9 (0.7) 5.5 (0.6) 5.4 (0.6)43.29 1.5e-2 7.5 (1) 7.3 (0.6) 7.7 (0.1)



RISE[mg/ml] run 10 run 27 run 284.5e-6 259.9 (11.6) 240.8 (5.4) 274 (13.4)1.5e-5 273.7 (10.1) 255.6 (3.2) 291.5 (12.1)4.5e-5 290.3 (8.4) 258.4 (5.2) 291.1 (19.2)1.5e-4 292.1 (13.7) 272.7 (6.5) 311.7 (8.2)4.5e-4 296.1 (13) 272.3 (10.2) 305.9 (24.5)1.5e-3 273.4 (2.4) 257 (10) 272.8 (11.9)4.5e-3 231.7 (5.8) 209.9 (2.5) 235 (9.2)1.5e-2 151.2(10.3) 138.5 (8.3) 143.8 (6.9)



300

D.41 Test item 41

−8 −7 −6 −50

20

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120

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160

180

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240

260

280

300

log10(M)

Re

lative

In

du

ctio

n [

%]


−8 −7 −6 −50

20

40

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100

120

140

160

180

200

220

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260

280

log10(M)

Re

lative

In

du

ctio

n [

%]


−8 −7 −6 −5

20

40

60

80

100

120

140

160

180

200

220

240

260

log10(M)

Re

lative

In

du

ctio

n [

%]




−8 −7 −6 −5

20

40

60

80

100

log10(M)

Rela

tive In

du

cti

on

[%

]


−8 −7 −6 −5

20

40

60

80

100

log10(M)

Rela

tive In

du

cti

on

[%

]


−8 −7 −6 −5

20

40

60

80

100

log10(M)

Rela

tive In

du

cti

on

[%

]





−8 −7 −6 −50

20

40

60

80

100

120

140

160

180

200

220

240

260

280

log10(M)

Rela

tive Induction [%

]

TI−06MG, RISE

run 10

run 16

run 30

Flutamide


301


[µM] [mg/ml] COM COM COM8.47e-3 4.5e-6 93.4 (0.8) 103.2 (0.4) 96 (5)2.82e-2 1.5e-5 97.7 (6.8) 101.8 (6.4) 90.3 (4.8)8.47e-2 4.5e-5 96.5 (2.1) 112.1 (3) 93 (2)2.82e-1 1.5e-4 95 (4) 94.6 (6.4) 91.8 (2.2)8.47e-1 4.5e-4 91.7 (1.9) 103.1(15.2) 83 (3.6)2.82 1.5e-3 77.3(7.2) 78.3(12.3) 64.2(2.3)8.47 4.5e-3 40.6(2.2) 44.3 (1.1) 33.2(2.7)28.23 1.5e-2 6.7 (1.3) 6.5 (1) 3.8 (1.1)



RISE[mg/ml] run 10 run 16 run 304.5e-6 268.9(6.8) 267.1 (24.8) 258.2 (8.6)1.5e-5 282.5(7.5) 274.1 (8.9) 253.6 (10.3)4.5e-5 282.7(1.8) 283.5 (13.5) 255.4 (15.2)1.5e-4 297.2(8.7) 268.1 (23.6) 246.2 (3.9)4.5e-4 278 (5) 264.1 (2.7) 241.6 (12.9)1.5e-3 255.2(8.7) 241.9 (5.6) 213.6 (11.6)4.5e-3 189 (8.7) 201.7 (3.7) 159.5 (1.1)1.5e-2 78.1(1.2) 64.1 (5.1) 51.7 (2.6)



302

D.42 Test item 42

−8 −7 −6 −50

20

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220

log10(M)

Re

lative

In

du

ctio

n [

%]


−8 −7 −6 −5

20

40

60

80

100

120

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180

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220

log10(M)

Re

lative

In

du

ctio

n [

%]


−8 −7 −6 −50

20

40

60

80

100

120

140

160

180

200

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240

260

log10(M)

Re

lative

In

du

ctio

n [

%]




−7 −6 −5

20

40

60

80

100

log10(M)

Rela

tive In

du

cti

on

[%

]


−7 −6 −5

20

40

60

80

100

log10(M)

Rela

tive In

du

cti

on

[%

]


−7 −6 −5

20

40

60

80

100

log10(M)

Rela

tive In

du

cti

on

[%

]





−8 −7 −6 −50

20

40

60

80

100

120

140

160

180

200

220

240

260

log10(M)

Rela

tive Induction [%

]

TI−14FX, RISE

run 12

run 24

run 28

Flutamide


303


[µM] [mg/ml] COM COM COM1.21e-2 4.5e-6 104 (4.6) 97 (3.5) 95.3 (4.7)4.03e-2 1.5e-5 103.7(4.8) 96.8 (1.2) 91.1 (6.1)1.21e-1 4.5e-5 94.2 (6) 112.5(1.8) 90.2 (1.6)4.03e-1 1.5e-4 80.2 (5) 73.2(1.4) 70.2(3.9)1.21 4.5e-4 57.7(5.7) 53.6(2.1) 53.1(5.1)4.03 1.5e-3 26.6(3.6) 22.1(0.4) 22.5(1.4)12.08 4.5e-3 6.6 (0.8) 6.5 (0.3) 6.3 (0.8)40.27 1.5e-2 1.1 (0.7) 0.7 (0.4) 0.9 (0.2)



RISE[mg/ml] run 12 run 24 run 284.5e-6 216 (6.3) 225.5 (4.5) 263.2 (2.9)1.5e-5 218.5 (12.1) 229.9 (5.8) 270.1 (4.8)4.5e-5 208.6 (2.8) 224.5 (5.6) 265.8 (7)1.5e-4 208.7 (3.2) 220.8 (9.8) 262.2 (10.3)4.5e-4 205.2 (7.5) 218.5 (8.1) 260.7 (15.4)1.5e-3 191 (3.1) 200.4 (2.9) 242 (3.7)4.5e-3 171.1(10.8) 186.2 (9.3) 218.6 (5)1.5e-2 142.4 (7.1) 145.1(2.3) 173.5 (8.3)



304

D.43 Test item 43

−9 −8 −7 −6 −50

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log10(M)

Rela

tive Induction [%

]TI−26XR, run 2, RISE

−9 −8 −7 −6 −50

20

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log10(M)

Rela

tive Induction [%

]


−9 −8 −7 −6 −50

20

40

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140

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180

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240

log10(M)

Rela

tive Induction [%

]




−9 −8 −7 −640

60

80

100

log10(M)

Rela

tive In

du

cti

on

[%

]


−9 −8 −7 −6

40

60

80

100

log10(M)

Rela

tive In

du

cti

on

[%

]


−9 −8 −7 −6

60

80

100

log10(M)

Rela

tive In

du

cti

on

[%

]

TI−26XR, run 8, RISE, int=82.26




−9 −8 −7 −6 −50

20

40

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240

260

log10(M)

Rela

tive Induction [%

]

TI−26XR, RISE

run 2

run 4

run 8

Flutamide


305


[µM] [mg/ml] COM COM COM7.42e-4 4.5e-7 97.9 (1.3) 103.9(3.6) 101.3 (5)2.47e-3 1.5e-6 95.4 (3.8) 99.1 (2.3) 100 (5)7.42e-3 4.5e-6 95.4 (4.7) 100.7(3.7) 96 (5.9)2.47e-2 1.5e-5 90.9 (3.4) 98.7 (2.9) 95.2 (1.2)7.42e-2 4.5e-5 88.7 (2.3) 100.4(8.1) 97.6 (3.9)2.47e-1 1.5e-4 89.4 (7.1) 91.7 (6.5) 89.1 (1.3)7.42e-1 4.5e-4 75.1 (8) 75.6(3.8) 111.5 (1.7)2.47 1.5e-3 41.3 (2) 43.3(3.8) 42.5 (0.9)interp value (x,y) (7.5e-4,82.3)

R2 0.97 0.9 0.76log10(PC80) [mg/ml] -3.46 -3.45 -2.96log10(IC50) [mg/ml] na -2.93 na


RISE[mg/ml] run 2 run 4 run 84.5e-7 241.5 (7.9) 261.5 (11.4) 252.4 (7.7)1.5e-6 236.6 (11) 264.6 (11.8) 244.8 (9.5)4.5e-6 236.2 (18.2) 271.5 (20.8) 241.1 (7)1.5e-5 228.6 (11) 269.8 (6.5) 250.9 (9.5)4.5e-5 229.1 (10.1) 267.4 (6.7) 244.9 (4.8)1.5e-4 217.9 (5.2) 270 (14.9) 236.3 (4.3)4.5e-4 210 (18) 250.9 (6) 225.5 (7.3)1.5e-3 171.6 (4.5) 186.4 (8.5) 163.3(10.8)



306

D.44 Test item 44

−8 −7 −6 −50

20

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320

log10(M)

Rela

tive Induction [%

]TI−21DS, run 13, RISE

−8 −7 −6 −5

20

40

60

80

100

120

140

160

180

200

220

log10(M)

Rela

tive Induction [%

]


−8 −7 −6 −50

20

40

60

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100

120

140

160

180

200

220

240

260

280

300

320

340

360

380

log10(M)

Rela

tive Induction [%

]




−8 −7 −6 −50

20

40

60

80

100

120

140

160

log10(M)

Re

lati

ve

In

du

cti

on

[%

]


−8 −7 −6

20

40

60

80

100

log10(M)

Rela

tive In

du

cti

on

[%

]


−8 −7 −6

20

40

60

80

100

120

log10(M)

Rela

tive In

du

cti

on

[%

]





−8 −7 −6 −50

20

40

60

80

100

120

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160

180

200

220

240

260

280

300

320

340

360

log10(M)

Rela

tive Induction [%

]

TI−21DS, RISE

run 13

run 22

run 34

Flutamide


307


[µM] [mg/ml] COM COM COM1.6e-3 4.5e-7 89.5 (2) 102.2(5.9)5.33e-3 1.5e-6 92.9 (7.4) 95.2 (6) 110.9(3.2)1.6e-2 4.5e-6 100.7(8.4) 109.3(5.3)1.78e-2 5e-6 91.5 (5.2)5.33e-2 1.5e-5 112.6(26.7) 96.5 (1.1) 117.8(3.3)1.6e-1 4.5e-5 107.3(1.8) 130.3(6.4)1.78e-1 5e-5 146.6(13.4)5.33e-1 1.5e-4 94.7 (6.3) 46.3(2.9) 72 (4.5)1.6 4.5e-4 9.4 (0.4) 14.7(0.8)1.78 5e-4 17.4 (0.9)5.33 1.5e-3 4 (0.5) 1.1 (0.3) 2 (0.3)17.77 5e-3 cyt/excl



RISE[mg/ml] run 13 run 22 run 344.5e-7 211.5 (1.8) 335.8 (13.4)1.5e-6 238.8 (7.6) 208.7(15.7) 345.5 (17.4)4.5e-6 223 (3.9) 343.2 (3.9)5e-6 253 (9.6)1.5e-5 259.8 (22.5) 221.4 (6.6) 375.2 (14.8)4.5e-5 221.5 (6.4) 369.5 (14.2)5e-5 313.1 (13.3)1.5e-4 179.3 (2.1) 82.4 (3.8) 202.8 (3.6)4.5e-4 17.8 (1.4) 33.5 (2.5)5e-4 37.5 (0.5)1.5e-3 8.1 (1.4) 2.8 (0.9) 3.7 (0.6)5e-3 cyt/excl



308

D.45 Test item 45

−11 −10 −9 −8 −7 −6 −50

20

40

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80

100

log10(M)

Re

lative

In

du

ctio

n [

%]


−11 −10 −9 −8 −7 −6 −50

20

40

60

80

100

log10(M)

Re

lative

In

du

ctio

n [

%]


−11 −10 −9 −8 −7 −6 −5

20

40

60

80

100

log10(M)

Re

lative

In

du

ctio

n [

%]




−11 −10 −9 −8 −7 −6 −50

20

40

60

80

100

log10(M)

Re

lative

In

du

ctio

n [

%]

TI−35VR, RISE

run 11

run 21

run 23

Flutamide



[µM] [mg/ml] PRE PRE PRE1.68e-6 5e-10 98.4 (4) 102.4(3.5) 90.3 (3.8)1.68e-5 5e-9 96.4 (3.7) 101 (2.1) 88.2 (4.9)1.68e-4 5e-8 97.5 (4.8) 95.1 (7.2) 87.7 (2.5)1.68e-3 5e-7 105.7(5.5) 100.7(6.5) 83.6 (2.9)1.68e-2 5e-6 96.4 (5.5) 97.7 (7.2) 81.7 (3.9)1.68e-1 5e-5 92.4 (4.7) 92.1 (9.7) 78 (2.9)1.68 5e-4 105.4(3.6) 107 (8.2) 100.2(0.6)16.76 5e-3 108.4(4.3) 110.5(0.6) 90 (2.7)

R2

log10(PC80) [mg/ml] -5.07log10(IC50) [mg/ml] na


309

D.46 Test item 46

−8 −7 −6 −50

20

40

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220

240

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300

320

340

log10(M)

Rela

tive Induction [%

]TI−02LU, run 10, RISE

−8 −7 −6 −5

20

40

60

80

100

120

140

160

180

200

220

240

260

280

log10(M)

Rela

tive Induction [%

]


−8 −7 −6 −5

20

40

60

80

100

120

140

160

180

200

220

240

260

280

300

log10(M)

Rela

tive Induction [%

]




−8 −7 −6 −5

20

40

60

80

100

log10(M)

Rela

tive In

du

cti

on

[%

]


−8 −7 −6 −5

20

40

60

80

100

log10(M)

Rela

tive In

du

cti

on

[%

]


−8 −7 −6

20

40

60

80

100

log10(M)

Rela

tive In

du

cti

on

[%

]





−8 −7 −6 −50

20

40

60

80

100

120

140

160

180

200

220

240

260

280

300

320

log10(M)

Rela

tive Induction [%

]

TI−02LU, RISE

run 10

run 27

run 30

Flutamide


310


[µM] [mg/ml] COM COM COM1.05e-3 4.5e-7 100 (3)3.49e-3 1.5e-6 93.3 (3.2) 94.5 (6.3) 95.9 (2.6)1.05e-2 4.5e-6 77.4(3.4)1.16e-2 5e-6 79.3 (9) 79.8(2.7)3.49e-2 1.5e-5 59.9(10.3) 53.9(1.8) 52.6(1.2)1.05e-1 4.5e-5 33 (2.5)1.16e-1 5e-5 35.3 (0.4) 33.6(1.8)3.49e-1 1.5e-4 22 (1.9) 23.1(1.3) 23.2(1.5)1.05 4.5e-4 19.7(2.1)1.16 5e-4 17.4 (1.5) 17.9(1.3)3.49 1.5e-3 16.6 (0.7) 15.7(1.2) 18.5 (1)11.64 5e-3 8.7 (1.1) 6.3 (0.1)



RISE[mg/ml] run 10 run 27 run 304.5e-7 286.7(14.8)1.5e-6 314.4 (16.1) 264.9 (3) 297.1 (14)4.5e-6 300.9 (2.6)5e-6 332.5 (16.2) 273.3(7.3)1.5e-5 328.3 (8.8) 274.1(7.6) 299.5 (9.6)4.5e-5 283.7(15.5)5e-5 324.2 (7) 268.5(6.7)1.5e-4 283.9 (15.7) 227.9 (6) 251.3 (2.2)4.5e-4 174 (6.7)5e-4 171.9 (6.1) 156 (5.3)1.5e-3 57.2 (3.2) 51.3(0.7) 53.6 (2.5)5e-3 11.4 (0.9) 10 (1.2)



311

D.47 Test item 3 (2)

−8 −7 −6 −50

20

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260

log10(M)

Rela

tive Induction [%

]TI−17AR, run 2, RISE

−8 −7 −6 −50

20

40

60

80

100

120

140

160

180

200

220

240

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280

log10(M)

Rela

tive Induction [%

]


−8 −7 −6 −50

20

40

60

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100

120

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220

log10(M)

Rela

tive Induction [%

]




−8 −7 −6

20

40

60

80

100

log10(M)

Rela

tive In

du

cti

on

[%

]


−8 −7 −6

20

40

60

80

100

log10(M)

Rela

tive In

du

cti

on

[%

]


−8 −7 −6

20

40

60

80

100

log10(M)

Rela

tive In

du

cti

on

[%

]





−8 −7 −6 −50

20

40

60

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260

log10(M)

Rela

tive Induction [%

]

TI−17AR, RISE

run 2

run 4

run 6

Flutamide


312


[µM] [mg/ml] COM COM COM1.08e-3 4.5e-7 101.4(3.6) 93.6 (4.2) 84 (5.1)3.6e-3 1.5e-6 90.7 (3.8) 94.4 (6.5) 81.7 (1.4)1.08e-2 4.5e-6 84.5 (2.4) 81.9 (4.4) 66.4(2.9)3.6e-2 1.5e-5 58.8 (1) 61.5(9.4) 46.8(1.4)1.08e-1 4.5e-5 39.2(1.2) 36.7(3.2) 31.2 (4)3.6e-1 1.5e-4 24.3(2.2) 23.9 (1) 19.2(0.4)1.08 4.5e-4 18.2(0.9) 19.1 (2) 17.4(0.8)3.6 1.5e-3 18.5(1.4) 19.5(0.8) 17.9(2.8)



RISE[mg/ml] run 2 run 4 run 64.5e-7 249.4 (10.1) 269.6(10.2) 207.2(12.9)1.5e-6 249.5 (4.2) 277.6(16.6) 214.2 (6.9)4.5e-6 242.9 (16.5) 272.8 (2.4) 217 (2.2)1.5e-5 235.2 (3.4) 266.1 (14) 203.2(18.4)4.5e-5 249.1 (17.3) 272.3(12.5) 205.3(10.1)1.5e-4 221.3 (10.3) 263.1(17.1) 189.5 (3.9)4.5e-4 200.1 (12.3) 226.6 (5.7) 168.9 (12)1.5e-3 118.1 (6.5) 136 (2.5) 90.1 (8.3)



313

List of abbreviations and definitions

BLR Between laboratory reproducibility

CALUX Chemically Activated LUciferase eXpression

DMSO Dimethylsulfoxide

DHT Dihydroxy testosterone

EC50 50% effective concentration

IC50 50% inhibitory concentration

NC Negative Control

PC Positive Control

RLU Relative Light Units

SC Solvent Control

WLR Within laboratory reproducibility

314

List of figures

Figure 1. Agonist testing. Boxplots for acceptance control variables. . . . . . . . . . 11Figure 2. Antagonist testing. Boxplots for acceptance control variables. . . . . . . . 12Figure 3. Test item 3. AG Responses for accepted experiments. Envigo. . . . . . . . 16Figure 4. Test item 8. AG Responses for accepted experiments. Envigo. . . . . . . . 16Figure 5. Test item 17. AG Responses for accepted experiments. RISE. . . . . . . . 17Figure 6. Test item 20. AG Responses for accepted experiments. Envigo. . . . . . . 17Figure 7. Test item 1. ANT Responses for accepted experiments. Envigo. . . . . . . 18Figure 8. Test item 1. ANT Responses for accepted experiments. BDS. . . . . . . . . 19Figure 9. Test item 4. ANT Responses for accepted experiments. Envigo. . . . . . . 19Figure 10.Test item 4. ANT Responses for accepted experiments. RISE. . . . . . . . 20Figure 11.Test item 8. ANT Responses for accepted experiments. Envigo and BDS. . 21Figure 12.Test item 9. ANT Responses for accepted experiments. Citoxlab and RISE. 21Figure 13.Test item 15. ANT Responses for accepted experiments. RISE. . . . . . . . 22Figure 14.Test item 18. ANT Responses for accepted experiments. RISE. . . . . . . . 22Figure 15.Test item 19. ANT Responses in participating labs aggregated by laboratory. 23Figure 16.Test item 19. ANT Responses in labs aggregated by laboratory and replicate. 24Figure 17.Test item 30. ANT Responses for accepted experiments. RISE. . . . . . . . 24Figure 18.Test item 34. ANT Responses for accepted experiments. RISE. . . . . . . . 25Figure 19.Test item 39. ANT Responses for accepted experiments. RISE. . . . . . . . 26Figure 20.Test item 43. ANT Responses for accepted experiments. RISE. . . . . . . . 26Figure 21.Variability of triplicates. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 39Figure 22.DHT. Within(Between) Run(Lab) Variability. . . . . . . . . . . . . . . . . . . 39Figure 23. [Flutamide. Within(Between) Run(Lab) Variability. . . . . . . . . . . . . . . 40Figure 24.Citoxlab,Study2 DHT responses. . . . . . . . . . . . . . . . . . . . . . . . . 55Figure 25.Envigo,Study2A DHT responses. . . . . . . . . . . . . . . . . . . . . . . . . 56Figure 26.Envigo,Study2B DHT responses. . . . . . . . . . . . . . . . . . . . . . . . . 56Figure 27.RISE,Study2 DHT responses. . . . . . . . . . . . . . . . . . . . . . . . . . . 57Figure 28.RISE,Study3 DHT responses. . . . . . . . . . . . . . . . . . . . . . . . . . . 58Figure 29.BDS,Study2 DHT responses. . . . . . . . . . . . . . . . . . . . . . . . . . . . 59Figure 30.Citoxlab,Study2 Flutamide responses. . . . . . . . . . . . . . . . . . . . . . 65Figure 31.Envigo,Study2A Flutamide responses. . . . . . . . . . . . . . . . . . . . . . 66Figure 32.Envigo,Study2B Flutamide responses. . . . . . . . . . . . . . . . . . . . . . 66Figure 33.RISE,Study2 Flutamide responses. . . . . . . . . . . . . . . . . . . . . . . . 67Figure 34.RISE,Study3 Flutamide responses. . . . . . . . . . . . . . . . . . . . . . . . 68Figure 35.BDS,Study2 Flutamide responses. . . . . . . . . . . . . . . . . . . . . . . . 69Figure 36.Test item 1. AG Responses in participarting labs. . . . . . . . . . . . . . . . 76Figure 37.Test item 1. AG Responses aggregated by laboratory. . . . . . . . . . . . . 77Figure 38.Test item 1. AG Responses aggregated by laboratory and replicates. . . . 77Figure 39.Test item 2. AG Responses in participarting labs. . . . . . . . . . . . . . . . 79Figure 40.Test item 2. AG Responses aggregated by laboratory. . . . . . . . . . . . . 80Figure 41.Test item 2. AG Responses aggregated by laboratory and replicates. . . . 80Figure 42.Test item 3. AG Responses in participarting labs. . . . . . . . . . . . . . . . 82Figure 43.Test item 3. AG Responses aggregated by laboratory. . . . . . . . . . . . . 83Figure 44.Test item 3. AG Responses aggregated by laboratory and replicates. . . . 83Figure 45.Test item 4. AG Responses in participarting labs. . . . . . . . . . . . . . . . 85Figure 46.Test item 4. AG Responses aggregated by laboratory. . . . . . . . . . . . . 86Figure 47.Test item 4. AG Responses aggregated by laboratory and replicates. . . . 86Figure 48.Test item 5. AG Responses in participarting labs. . . . . . . . . . . . . . . . 88Figure 49.Test item 5. AG Responses aggregated by laboratory. . . . . . . . . . . . . 89

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Figure 50.Test item 5. AG Responses aggregated by laboratory and replicates. . . . 89Figure 51.Test item 6. AG Responses in participarting labs. . . . . . . . . . . . . . . . 91Figure 52.Test item 6. AG Responses aggregated by laboratory. . . . . . . . . . . . . 92Figure 53.Test item 6. AG Responses aggregated by laboratory and replicates. . . . 92Figure 54.Test item 7. AG Responses in participarting labs. . . . . . . . . . . . . . . . 94Figure 55.Test item 7. AG Responses aggregated by laboratory. . . . . . . . . . . . . 95Figure 56.Test item 7. AG Responses aggregated by laboratory and replicates. . . . 95Figure 57.Test item 8. AG Responses in participarting labs. . . . . . . . . . . . . . . . 97Figure 58.Test item 8. AG Responses aggregated by laboratory. . . . . . . . . . . . . 98Figure 59.Test item 8. AG Responses aggregated by laboratory and replicates. . . . 98Figure 60.Test item 9. AG Responses in participarting labs. . . . . . . . . . . . . . . . 100Figure 61.Test item 9. AG Responses aggregated by laboratory. . . . . . . . . . . . . 101Figure 62.Test item 9. AG Responses aggregated by laboratory and replicates. . . . 101Figure 63.Test item 10. AG Responses in participarting labs. . . . . . . . . . . . . . . 103Figure 64.Test item 10. AG Responses aggregated by laboratory. . . . . . . . . . . . 104Figure 65.Test item 10. AG Responses aggregated by laboratory and replicates. . . . 104Figure 66.Test item 11. AG Responses in participarting labs. . . . . . . . . . . . . . . 106Figure 67.Test item 11. AG Responses aggregated by laboratory. . . . . . . . . . . . 107Figure 68.Test item 11. AG Responses aggregated by laboratory and replicates. . . . 107Figure 69.Test item 12. AG Responses in participarting labs. . . . . . . . . . . . . . . 109Figure 70.Test item 12. AG Responses aggregated by laboratory. . . . . . . . . . . . 110Figure 71.Test item 12. AG Responses aggregated by laboratory and replicates. . . . 110Figure 72.Test item 13. AG Responses in participarting labs. . . . . . . . . . . . . . . 112Figure 73.Test item 13. AG Responses aggregated by laboratory. . . . . . . . . . . . 113Figure 74.Test item 13. AG Responses aggregated by laboratory and replicates. . . . 113Figure 75.Test item 14. AG Responses in participarting labs. . . . . . . . . . . . . . . 115Figure 76.Test item 14. AG Responses aggregated by laboratory. . . . . . . . . . . . 116Figure 77.Test item 14. AG Responses aggregated by laboratory and replicates. . . . 116Figure 78.Test item 15. AG Responses in participarting labs. . . . . . . . . . . . . . . 118Figure 79.Test item 15. AG Responses aggregated by laboratory. . . . . . . . . . . . 119Figure 80.Test item 15. AG Responses aggregated by laboratory and replicates. . . . 119Figure 81.Test item 16. AG Responses in participarting labs. . . . . . . . . . . . . . . 121Figure 82.Test item 16. AG Responses aggregated by laboratory. . . . . . . . . . . . 122Figure 83.Test item 16. AG Responses aggregated by laboratory and replicates. . . . 122Figure 84.Test item 17. AG Responses in participarting labs. . . . . . . . . . . . . . . 124Figure 85.Test item 17. AG Responses aggregated by laboratory. . . . . . . . . . . . 125Figure 86.Test item 17. AG Responses aggregated by laboratory and replicates. . . . 125Figure 87.Test item 18. AG Responses in participarting labs. . . . . . . . . . . . . . . 127Figure 88.Test item 18. AG Responses aggregated by laboratory. . . . . . . . . . . . 128Figure 89.Test item 18. AG Responses aggregated by laboratory and replicates. . . . 128Figure 90.Test item 19. AG Responses in participarting labs. . . . . . . . . . . . . . . 130Figure 91.Test item 19. AG Responses aggregated by laboratory. . . . . . . . . . . . 131Figure 92.Test item 19. AG Responses aggregated by laboratory and replicates. . . . 131Figure 93.Test item 20. AG Responses in participarting labs. . . . . . . . . . . . . . . 133Figure 94.Test item 20. AG Responses aggregated by laboratory. . . . . . . . . . . . 134Figure 95.Test item 20. AG Responses aggregated by laboratory and replicates. . . . 134Figure 96.Test item 21. AG Responses in participarting labs. . . . . . . . . . . . . . . 136Figure 97.Test item 21. AG Responses aggregated by laboratory. . . . . . . . . . . . 136Figure 98.Test item 22. AG Responses in participarting labs. . . . . . . . . . . . . . . 137Figure 99.Test item 22. AG Responses aggregated by laboratory. . . . . . . . . . . . 137Figure 100.Test item 23. AG Responses in participarting labs. . . . . . . . . . . . . . . 138

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Figure 101.Test item 23. AG Responses aggregated by laboratory. . . . . . . . . . . . 138Figure 102.Test item 24. AG Responses in participarting labs. . . . . . . . . . . . . . . 139Figure 103.Test item 24. AG Responses aggregated by laboratory. . . . . . . . . . . . 139Figure 104.Test item 25. AG Responses in participarting labs. . . . . . . . . . . . . . . 140Figure 105.Test item 25. AG Responses aggregated by laboratory. . . . . . . . . . . . 140Figure 106.Test item 26. AG Responses in participarting labs. . . . . . . . . . . . . . . 141Figure 107.Test item 26. AG Responses aggregated by laboratory. . . . . . . . . . . . 141Figure 108.Test item 27. AG Responses in participarting labs. . . . . . . . . . . . . . . 142Figure 109.Test item 27. AG Responses aggregated by laboratory. . . . . . . . . . . . 142Figure 110.Test item 28. AG Responses in participarting labs. . . . . . . . . . . . . . . 143Figure 111.Test item 28. AG Responses aggregated by laboratory. . . . . . . . . . . . 143Figure 112.Test item 29. AG Responses in participarting labs. . . . . . . . . . . . . . . 144Figure 113.Test item 29. AG Responses aggregated by laboratory. . . . . . . . . . . . 144Figure 114.Test item 30. AG Responses in participarting labs. . . . . . . . . . . . . . . 145Figure 115.Test item 30. AG Responses aggregated by laboratory. . . . . . . . . . . . 145Figure 116.Test item 31. AG Responses in participarting labs. . . . . . . . . . . . . . . 146Figure 117.Test item 31. AG Responses aggregated by laboratory. . . . . . . . . . . . 146Figure 118.Test item 32. AG Responses in participarting labs. . . . . . . . . . . . . . . 147Figure 119.Test item 32. AG Responses aggregated by laboratory. . . . . . . . . . . . 147Figure 120.Test item 33. AG Responses in participarting labs. . . . . . . . . . . . . . . 148Figure 121.Test item 33. AG Responses aggregated by laboratory. . . . . . . . . . . . 148Figure 122.Test item 34. AG Responses in participarting labs. . . . . . . . . . . . . . . 149Figure 123.Test item 34. AG Responses aggregated by laboratory. . . . . . . . . . . . 149Figure 124.Test item 35. AG Responses in participarting labs. . . . . . . . . . . . . . . 150Figure 125.Test item 35. AG Responses aggregated by laboratory. . . . . . . . . . . . 150Figure 126.Test item 36. AG Responses in participarting labs. . . . . . . . . . . . . . . 151Figure 127.Test item 36. AG Responses aggregated by laboratory. . . . . . . . . . . . 151Figure 128.Test item 37. AG Responses in participarting labs. . . . . . . . . . . . . . . 152Figure 129.Test item 37. AG Responses aggregated by laboratory. . . . . . . . . . . . 152Figure 130.Test item 38. AG Responses in participarting labs. . . . . . . . . . . . . . . 153Figure 131.Test item 38. AG Responses aggregated by laboratory. . . . . . . . . . . . 153Figure 132.Test item 39. AG Responses in participarting labs. . . . . . . . . . . . . . . 154Figure 133.Test item 39. AG Responses aggregated by laboratory. . . . . . . . . . . . 154Figure 134.Test item 40. AG Responses in participarting labs. . . . . . . . . . . . . . . 155Figure 135.Test item 40. AG Responses aggregated by laboratory. . . . . . . . . . . . 155Figure 136.Test item 41. AG Responses in participarting labs. . . . . . . . . . . . . . . 156Figure 137.Test item 41. AG Responses aggregated by laboratory. . . . . . . . . . . . 156Figure 138.Test item 42. AG Responses in participarting labs. . . . . . . . . . . . . . . 157Figure 139.Test item 42. AG Responses aggregated by laboratory. . . . . . . . . . . . 157Figure 140.Test item 43. AG Responses in participarting labs. . . . . . . . . . . . . . . 158Figure 141.Test item 43. AG Responses aggregated by laboratory. . . . . . . . . . . . 158Figure 142.Test item 44. AG Responses in participarting labs. . . . . . . . . . . . . . . 159Figure 143.Test item 44. AG Responses aggregated by laboratory. . . . . . . . . . . . 159Figure 144.Test item 45. AG Responses in participarting labs. . . . . . . . . . . . . . . 160Figure 145.Test item 45. AG Responses aggregated by laboratory. . . . . . . . . . . . 160Figure 146.Test item 46. AG Responses in participarting labs. . . . . . . . . . . . . . . 161Figure 147.Test item 46. AG Responses aggregated by laboratory. . . . . . . . . . . . 161Figure 148.Test item 47. AG Responses in participarting labs. . . . . . . . . . . . . . . 162Figure 149.Test item 47. AG Responses aggregated by laboratory. . . . . . . . . . . . 162Figure 150.Test item 1. ANT Responses in participarting labs. . . . . . . . . . . . . . . 164Figure 151.Test item 1. ANT Normalized Responses in participarting labs. . . . . . . . 165

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Figure 152.Test item 1. ANT Responses aggregated by laboratory. . . . . . . . . . . . 166Figure 153.Test item 1. ANT Responses aggregated by laboratory and replicates. . . . 169Figure 154.Test item 2. ANT Responses in participarting labs. . . . . . . . . . . . . . . 170Figure 155.Test item 2. ANT Responses aggregated by laboratory. . . . . . . . . . . . 171Figure 156.Test item 2. ANT Responses aggregated by laboratory and replicates. . . . 173Figure 157.Test item 3. ANT Responses in participarting labs. . . . . . . . . . . . . . . 174Figure 158.Test item 3. ANT Normalized Responses in participarting labs. . . . . . . . 175Figure 159.Test item 3. ANT Responses aggregated by laboratory. . . . . . . . . . . . 176Figure 160.Test item 3. ANT Responses aggregated by laboratory and replicates. . . . 179Figure 161.Test item 4. ANT Responses in participarting labs. . . . . . . . . . . . . . . 180Figure 162.Test item 4. ANT Normalized Responses in participarting labs. . . . . . . . 181Figure 163.Test item 4. ANT Responses aggregated by laboratory. . . . . . . . . . . . 182Figure 164.Test item 4. ANT Responses aggregated by laboratory and replicates. . . . 185Figure 165.Test item 5. ANT Responses in participarting labs. . . . . . . . . . . . . . . 186Figure 166.Test item 5. ANT Normalized Responses in participarting labs. . . . . . . . 187Figure 167.Test item 5. ANT Responses aggregated by laboratory. . . . . . . . . . . . 188Figure 168.Test item 5. ANT Responses aggregated by laboratory and replicates. . . . 191Figure 169.Test item 6. ANT Responses in participarting labs. . . . . . . . . . . . . . . 192Figure 170.Test item 6. ANT Normalized Responses in participarting labs. . . . . . . . 193Figure 171.Test item 6. ANT Responses aggregated by laboratory. . . . . . . . . . . . 194Figure 172.Test item 6. ANT Responses aggregated by laboratory and replicates. . . . 197Figure 173.Test item 7. ANT Responses in participarting labs. . . . . . . . . . . . . . . 198Figure 174.Test item 7. ANT Responses aggregated by laboratory. . . . . . . . . . . . 199Figure 175.Test item 7. ANT Responses aggregated by laboratory and replicates. . . . 201Figure 176.Test item 8. ANT Responses in participarting labs. . . . . . . . . . . . . . . 202Figure 177.Test item 8. ANT Responses aggregated by laboratory. . . . . . . . . . . . 203Figure 178.Test item 8. ANT Responses aggregated by laboratory and replicates. . . . 205Figure 179.Test item 9. ANT Responses in participarting labs. . . . . . . . . . . . . . . 206Figure 180.Test item 9. ANT Normalized Responses in participarting labs. . . . . . . . 207Figure 181.Test item 9. ANT Responses aggregated by laboratory. . . . . . . . . . . . 208Figure 182.Test item 9. ANT Responses aggregated by laboratory and replicates. . . . 211Figure 183.Test item 10. ANT Responses in participarting labs. . . . . . . . . . . . . . 212Figure 184.Test item 10. ANT Normalized Responses in participarting labs. . . . . . . 213Figure 185.Test item 10. ANT Responses aggregated by laboratory. . . . . . . . . . . . 214Figure 186.Test item 10. ANT Responses aggregated by laboratory and replicates. . . 217Figure 187.Test item 11. ANT Responses in participarting labs. . . . . . . . . . . . . . 218Figure 188.Test item 11. ANT Responses aggregated by laboratory. . . . . . . . . . . . 219Figure 189.Test item 11. ANT Responses aggregated by laboratory and replicates. . . 221Figure 190.Test item 12. ANT Responses in participarting labs. . . . . . . . . . . . . . 222Figure 191.Test item 12. ANT Responses aggregated by laboratory. . . . . . . . . . . . 223Figure 192.Test item 12. ANT Responses aggregated by laboratory and replicates. . . 225Figure 193.Test item 13. ANT Responses in participarting labs. . . . . . . . . . . . . . 226Figure 194.Test item 13. ANT Responses aggregated by laboratory. . . . . . . . . . . . 227Figure 195.Test item 13. ANT Responses aggregated by laboratory and replicates. . . 229Figure 196.Test item 14. ANT Responses in participarting labs. . . . . . . . . . . . . . 230Figure 197.Test item 14. ANT Normalized Responses in participarting labs. . . . . . . 231Figure 198.Test item 14. ANT Responses aggregated by laboratory. . . . . . . . . . . . 232Figure 199.Test item 14. ANT Responses aggregated by laboratory and replicates. . . 235Figure 200.Test item 15. ANT Responses in participarting labs. . . . . . . . . . . . . . 236Figure 201.Test item 15. ANT Normalized Responses in participarting labs. . . . . . . 237Figure 202.Test item 15. ANT Responses aggregated by laboratory. . . . . . . . . . . . 238

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Figure 203.Test item 15. ANT Responses aggregated by laboratory and replicates. . . 241Figure 204.Test item 16. ANT Responses in participarting labs. . . . . . . . . . . . . . 242Figure 205.Test item 16. ANT Responses aggregated by laboratory. . . . . . . . . . . . 243Figure 206.Test item 16. ANT Responses aggregated by laboratory and replicates. . . 245Figure 207.Test item 17. ANT Responses in participarting labs. . . . . . . . . . . . . . 246Figure 208.Test item 17. ANT Normalized Responses in participarting labs. . . . . . . 247Figure 209.Test item 17. ANT Responses aggregated by laboratory. . . . . . . . . . . . 248Figure 210.Test item 17. ANT Responses aggregated by laboratory and replicates. . . 251Figure 211.Test item 18. ANT Responses in participarting labs. . . . . . . . . . . . . . 252Figure 212.Test item 18. ANT Normalized Responses in participarting labs. . . . . . . 253Figure 213.Test item 18. ANT Responses aggregated by laboratory. . . . . . . . . . . . 254Figure 214.Test item 18. ANT Responses aggregated by laboratory and replicates. . . 257Figure 215.Test item 19. ANT Responses in participarting labs. . . . . . . . . . . . . . 258Figure 216.Test item 19. ANT Normalized Responses in participarting labs. . . . . . . 259Figure 217.Test item 19. ANT Responses aggregated by laboratory. . . . . . . . . . . . 260Figure 218.Test item 19. ANT Responses aggregated by laboratory and replicates. . . 263Figure 219.Test item 20. ANT Responses in participarting labs. . . . . . . . . . . . . . 264Figure 220.Test item 20. ANT Normalized Responses in participarting labs. . . . . . . 265Figure 221.Test item 20. ANT Responses aggregated by laboratory. . . . . . . . . . . . 266Figure 222.Test item 20. ANT Responses aggregated by laboratory and replicates. . . 269Figure 223.Test item 21. ANT Responses in participarting labs. . . . . . . . . . . . . . 270Figure 224.Test item 21. ANT Responses aggregated by laboratory. . . . . . . . . . . . 270Figure 225.Test item 22. ANT Responses in participarting labs. . . . . . . . . . . . . . 271Figure 226.Test item 22. ANT Normalized Responses in participarting labs. . . . . . . 271Figure 227.Test item 22. ANT Responses aggregated by laboratory. . . . . . . . . . . . 271Figure 228.Test item 23. ANT Responses in participarting labs. . . . . . . . . . . . . . 273Figure 229.Test item 23. ANT Normalized Responses in participarting labs. . . . . . . 273Figure 230.Test item 23. ANT Responses aggregated by laboratory. . . . . . . . . . . . 273Figure 231.Test item 24. ANT Responses in participarting labs. . . . . . . . . . . . . . 275Figure 232.Test item 24. ANT Normalized Responses in participarting labs. . . . . . . 275Figure 233.Test item 24. ANT Responses aggregated by laboratory. . . . . . . . . . . . 275Figure 234.Test item 25. ANT Responses in participarting labs. . . . . . . . . . . . . . 277Figure 235.Test item 25. ANT Responses aggregated by laboratory. . . . . . . . . . . . 277Figure 236.Test item 26. ANT Responses in participarting labs. . . . . . . . . . . . . . 278Figure 237.Test item 26. ANT Normalized Responses in participarting labs. . . . . . . 278Figure 238.Test item 26. ANT Responses aggregated by laboratory. . . . . . . . . . . . 278Figure 239.Test item 27. ANT Responses in participarting labs. . . . . . . . . . . . . . 280Figure 240.Test item 27. ANT Responses aggregated by laboratory. . . . . . . . . . . . 280Figure 241.Test item 28. ANT Responses in participarting labs. . . . . . . . . . . . . . 281Figure 242.Test item 28. ANT Responses aggregated by laboratory. . . . . . . . . . . . 281Figure 243.Test item 29. ANT Responses in participarting labs. . . . . . . . . . . . . . 282Figure 244.Test item 29. ANT Responses aggregated by laboratory. . . . . . . . . . . . 282Figure 245.Test item 30. ANT Responses in participarting labs. . . . . . . . . . . . . . 283Figure 246.Test item 30. ANT Normalized Responses in participarting labs. . . . . . . 283Figure 247.Test item 30. ANT Responses aggregated by laboratory. . . . . . . . . . . . 283Figure 248.Test item 31. ANT Responses in participarting labs. . . . . . . . . . . . . . 285Figure 249.Test item 31. ANT Normalized Responses in participarting labs. . . . . . . 285Figure 250.Test item 31. ANT Responses aggregated by laboratory. . . . . . . . . . . . 285Figure 251.Test item 32. ANT Responses in participarting labs. . . . . . . . . . . . . . 287Figure 252.Test item 32. ANT Responses aggregated by laboratory. . . . . . . . . . . . 287Figure 253.Test item 33. ANT Responses in participarting labs. . . . . . . . . . . . . . 288

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Figure 254.Test item 33. ANT Responses aggregated by laboratory. . . . . . . . . . . . 288Figure 255.Test item 34. ANT Responses in participarting labs. . . . . . . . . . . . . . 289Figure 256.Test item 34. ANT Normalized Responses in participarting labs. . . . . . . 289Figure 257.Test item 34. ANT Responses aggregated by laboratory. . . . . . . . . . . . 289Figure 258.Test item 35. ANT Responses in participarting labs. . . . . . . . . . . . . . 291Figure 259.Test item 35. ANT Responses aggregated by laboratory. . . . . . . . . . . . 291Figure 260.Test item 36. ANT Responses in participarting labs. . . . . . . . . . . . . . 292Figure 261.Test item 36. ANT Normalized Responses in participarting labs. . . . . . . 292Figure 262.Test item 36. ANT Responses aggregated by laboratory. . . . . . . . . . . . 292Figure 263.Test item 37. ANT Responses in participarting labs. . . . . . . . . . . . . . 294Figure 264.Test item 37. ANT Normalized Responses in participarting labs. . . . . . . 294Figure 265.Test item 37. ANT Responses aggregated by laboratory. . . . . . . . . . . . 294Figure 266.Test item 38. ANT Responses in participarting labs. . . . . . . . . . . . . . 296Figure 267.Test item 38. ANT Responses aggregated by laboratory. . . . . . . . . . . . 296Figure 268.Test item 39. ANT Responses in participarting labs. . . . . . . . . . . . . . 297Figure 269.Test item 39. ANT Normalized Responses in participarting labs. . . . . . . 297Figure 270.Test item 39. ANT Responses aggregated by laboratory. . . . . . . . . . . . 297Figure 271.Test item 40. ANT Responses in participarting labs. . . . . . . . . . . . . . 299Figure 272.Test item 40. ANT Normalized Responses in participarting labs. . . . . . . 299Figure 273.Test item 40. ANT Responses aggregated by laboratory. . . . . . . . . . . . 299Figure 274.Test item 41. ANT Responses in participarting labs. . . . . . . . . . . . . . 301Figure 275.Test item 41. ANT Normalized Responses in participarting labs. . . . . . . 301Figure 276.Test item 41. ANT Responses aggregated by laboratory. . . . . . . . . . . . 301Figure 277.Test item 42. ANT Responses in participarting labs. . . . . . . . . . . . . . 303Figure 278.Test item 42. ANT Normalized Responses in participarting labs. . . . . . . 303Figure 279.Test item 42. ANT Responses aggregated by laboratory. . . . . . . . . . . . 303Figure 280.Test item 43. ANT Responses in participarting labs. . . . . . . . . . . . . . 305Figure 281.Test item 43. ANT Normalized Responses in participarting labs. . . . . . . 305Figure 282.Test item 43. ANT Responses aggregated by laboratory. . . . . . . . . . . . 305Figure 283.Test item 44. ANT Responses in participarting labs. . . . . . . . . . . . . . 307Figure 284.Test item 44. ANT Normalized Responses in participarting labs. . . . . . . 307Figure 285.Test item 44. ANT Responses aggregated by laboratory. . . . . . . . . . . . 307Figure 286.Test item 45. ANT Responses in participarting labs. . . . . . . . . . . . . . 309Figure 287.Test item 45. ANT Responses aggregated by laboratory. . . . . . . . . . . . 309Figure 288.Test item 46. ANT Responses in participarting labs. . . . . . . . . . . . . . 310Figure 289.Test item 46. ANT Normalized Responses in participarting labs. . . . . . . 310Figure 290.Test item 46. ANT Responses aggregated by laboratory. . . . . . . . . . . . 310Figure 291.Test item 47. ANT Responses in participarting labs. . . . . . . . . . . . . . 312Figure 292.Test item 47. ANT Normalized Responses in participarting labs. . . . . . . 312Figure 293.Test item 47. ANT Responses aggregated by laboratory. . . . . . . . . . . . 312

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List of tables

Table 1. Test item codes as assigned by EURL ECVAM. . . . . . . . . . . . . . . . . . 3Table 2. Number of accepted/rejected experiments . . . . . . . . . . . . . . . . . . . 8Table 3. Agonist testing. Acceptance criteria statistics across all runs. . . . . . . . . 9Table 4. Antagonist testing. Acceptance criteria statistics across all runs. . . . . . . 10Table 5. Assigned classification for Test items 1 to 20. . . . . . . . . . . . . . . . . . 14Table 6. Assigned classification for Test items 21 to 46. . . . . . . . . . . . . . . . . . 14Table 7. WLR . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 27Table 8. BLR . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 27Table 9. Assigned classification per lab based on the majority rule. i.e. 2 out of 3 rule. 28Table 10.Assigned classification per lab based on the majority rule. i.e. 2 out of 3

rule. RISE, Test items 21-46. . . . . . . . . . . . . . . . . . . . . . . . . . . . 28Table 11.Agonist testing. Overview of averaged PC10 values.[mg/ml] . . . . . . . . . 29Table 12.Agonist testing. Overview of averaged EC50 values. [mg/ml] . . . . . . . . 29Table 13.Antagonist testing. Overview of averaged PC80 values. [mg/ml] . . . . . . 30Table 14.Antagonist testing. Overview of averaged IC50 values. [mg/ml] . . . . . . 30Table 15.Agonist testing. Overview of EC50. . . . . . . . . . . . . . . . . . . . . . . . 31Table 16.Agonist testing. Overview of PC10. . . . . . . . . . . . . . . . . . . . . . . . 31Table 17.Agonist testing. RISE. Test items 21-46. Overview of EC50 and PC10. . . . 32Table 18.Agonist testing. Overview of log(EC50). . . . . . . . . . . . . . . . . . . . . . 33Table 19.Agonist testing. Overview of CV(log(EC50)) [%] . . . . . . . . . . . . . . . . 33Table 20.Agonist testing. Overview of log(PC10). . . . . . . . . . . . . . . . . . . . . . 34Table 21.Agonist testing. RISE. Test items 21-46. Overview of log(EC50), CV(log(EC50))

and log(PC10). . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 34Table 22.Antagonist testing. Overview of IC50. . . . . . . . . . . . . . . . . . . . . . . 35Table 23.Antagonist testing. Overview of PC80. . . . . . . . . . . . . . . . . . . . . . 35Table 24.Antagonist testing. RISE. Test items 21-46. Overview of IC50 and PC80.

[mg/ml] . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 36Table 25.Antagonist testing. Overview of log(IC50). . . . . . . . . . . . . . . . . . . . 36Table 26.Antagonist testing. Overview of CV(log(IC50)) [%]. . . . . . . . . . . . . . . 37Table 27.Antagonist testing. Overview of log(PC80). . . . . . . . . . . . . . . . . . . . 37Table 28.Antagonist testing. RISE. Test items 21-46. Overview of log(IC50) and

log(PC80) [mg/ml] . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 38Table 29.Citoxlab. Study2. Overview of accepted runs. . . . . . . . . . . . . . . . . . 41Table 30.Envigo. Study2A. Overview of accepted runs. . . . . . . . . . . . . . . . . . 41Table 31.Envigo. Study2B. Overview of accepted runs. . . . . . . . . . . . . . . . . . 41Table 32.RISE. Study2. Overview of accepted runs. . . . . . . . . . . . . . . . . . . . 41Table 33.RISE. Study3. Overview of accepted runs. . . . . . . . . . . . . . . . . . . . 42Table 34.BDS. Study2. Overview of accepted runs. . . . . . . . . . . . . . . . . . . . 42Table 35.Citoxlab. Study2. Overview of three accepted runs per Test item. . . . . . . 43Table 36.Envigo. Study2A. Overview of three accepted runs per Test item. . . . . . . 43Table 37.Envigo. Study2B. Overview of three accepted runs per Test item. . . . . . . 43Table 38.RISE. Study2. Overview of three accepted runs per Test item. . . . . . . . . 43Table 39.RISE. Study3. Overview of three accepted runs per Test item. . . . . . . . . 44Table 40.BDS. Study2. Overview of three accepted runs per Test item. . . . . . . . . 44Table 41.Citoxlab. Study2. Agonist testing. Overview of the highest tested concen-

trations in three accepted runs together with prescreen (where applicable).Last three colums reffer to three accepted runs (either all prescreen or com-prehensive). The first column refferes to the prescreen when 3 acceptedruns are comprehensive. Label "cyt" denotes cytotoxic concentrations. . . 45

321

Table 42.Envigo. Study2A. Agonist testing. Overview of the highest tested concen-trations in three accepted runs together with prescreen (where applicable).Last three colums reffer to three accepted runs (either all prescreen or com-prehensive). The first column refferes to the prescreen when 3 acceptedruns are comprehensive. Label "cyt" denotes cytotoxic concentrations. . . 45

Table 43.Envigo. Study2B. Agonist testing. Overview of the highest tested concen-trations in three accepted runs together with prescreen (where applicable).Last three colums reffer to three accepted runs (either all prescreen or com-prehensive). The first column refferes to the prescreen when 3 acceptedruns are comprehensive. Label "cyt" denotes cytotoxic concentrations. . . 45

Table 44.RISE. Study2. Agonist testing. Overview of the highest tested concentra-tions in three accepted runs together with prescreen (where applicable).Last three colums reffer to three accepted runs (either all prescreen or com-prehensive). The first column refferes to the prescreen when 3 acceptedruns are comprehensive. Label "cyt" denotes cytotoxic concentrations. . . 46

Table 45.RISE. Study3. Agonist testing. Overview of the highest tested concentra-tions in three accepted runs together with prescreen (where applicable).Last three colums reffer to three accepted runs (either all prescreen or com-prehensive). The first column refferes to the prescreen when 3 acceptedruns are comprehensive. Label "cyt" denotes cytotoxic concentrations. . . 46

Table 46.BDS. Study2. Agonist testing. Overview of the highest tested concentra-tions in three accepted runs together with prescreen (where applicable).Last three colums reffer to three accepted runs (either all prescreen or com-prehensive). The first column refferes to the prescreen when 3 acceptedruns are comprehensive. Label "cyt" denotes cytotoxic concentrations. . . 47

Table 47.Citoxlab. Study2. Antagonist testing. Overview of accepted runs. . . . . . . 47Table 48.Envigo. Study2A. Antagonist testing. Overview of accepted runs. . . . . . . 47Table 49.Envigo. Study2B. Antagonist testing. Overview of accepted runs. . . . . . . 48Table 50.RISE. Study2. Antagonist testing. Overview of accepted runs. . . . . . . . . 48Table 51.RISE. Study3. Antagonist testing. Overview of accepted runs. . . . . . . . . 48Table 52.BDS. Study2. Antagonist testing. Overview of accepted runs. . . . . . . . . 49Table 53.Citoxlab. Study2. Antagonist testing. Overview of three accepted runs per

Test item. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 50Table 54.Envigo. Study2A. Antagonist testing. Overview of three accepted runs per

Test item. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 50Table 55.Envigo. Study2B. Antagonist testing. Overview of three accepted runs per

Test item. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 50Table 56.RISE. Study2. Antagonist testing. Overview of three accepted runs per Test

item. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 50Table 57.RISE. Study3. Antagonist testing. Overview of three accepted runs per Test

item. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 51Table 58.BDS. Study2. Antagonist testing. Overview of three accepted runs per Test

item. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 51Table 59.Citoxlab. Study2. Antagonist testing. Overview of the highest tested con-

centrations in three accepted runs together with prescreen (where applica-ble). Last three colums reffer to three accepted runs (either all prescreen orcomprehensive). The first column refferes to the prescreen when 3 acceptedruns are comprehensive. Label "cyt" denotes cytotoxic concentrations. . . 52

322

Table 60.Envigo. Study2A. Antagonist testing. Overview of the highest tested con-centrations in three accepted runs together with prescreen (where applica-ble). Last three colums reffer to three accepted runs (either all prescreen orcomprehensive). The first column refferes to the prescreen when 3 acceptedruns are comprehensive. Label "cyt" denotes cytotoxic concentrations. . . 52

Table 61.Envigo. Study2B. Antagonist testing. Overview of the highest tested con-centrations in three accepted runs together with prescreen (where applica-ble). Last three colums reffer to three accepted runs (either all prescreen orcomprehensive). The first column refferes to the prescreen when 3 acceptedruns are comprehensive. Label "cyt" denotes cytotoxic concentrations. . . 52

Table 62.RISE. Study2. Antagonist testing. Overview of the highest tested concen-trations in three accepted runs together with prescreen (where applicable).Last three colums reffer to three accepted runs (either all prescreen or com-prehensive). The first column refferes to the prescreen when 3 acceptedruns are comprehensive. Label "cyt" denotes cytotoxic concentrations. . . 53

Table 63.RISE. Study3. Antagonist testing. Overview of the highest tested concen-trations in three accepted runs together with prescreen (where applicable).Last three colums reffer to three accepted runs (either all prescreen or com-prehensive). The first column refferes to the prescreen when 3 acceptedruns are comprehensive. Label "cyt" denotes cytotoxic concentrations. . . 53

Table 64.BDS. Study2. Antagonist testing. Overview of the highest tested concen-trations in three accepted runs together with prescreen (where applicable).Last three colums reffer to three accepted runs (either all prescreen or com-prehensive). The first column refferes to the prescreen when 3 acceptedruns are comprehensive. Label "cyt" denotes cytotoxic concentrations. . . 54

Table 65.Citoxlab. Study2. Acceptance criteria: Induction factor, Z-factor. . . . . . . 60Table 66.Envigo. Study2A. Acceptance criteria: Induction factor, Z-factor. . . . . . . 60Table 67.Envigo. Study2B. Acceptance criteria: Induction factor, Z-factor. . . . . . . 60Table 68.RISE. Study2. Acceptance criteria: Induction factor, Z-factor. . . . . . . . . 60Table 69.RISE. Study3. Acceptance criteria: Induction factor, Z-factor. . . . . . . . . 61Table 70.BDS. Study2. Acceptance criteria: Induction factor, Z-factor. . . . . . . . . 61Table 71.Citoxlab. Study2. Acceptance criteria: EC50 [M], log10(EC50), CV(EC50)

[%], PC, NC. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 62Table 72.Envigo. Study2A. Acceptance criteria: EC50 [M], log10(EC50), CV(EC50)

[%], PC, NC. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 62Table 73.Envigo. Study2B. Acceptance criteria: EC50 [M], log10(EC50), CV(EC50)

[%], PC, NC. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 62Table 74.RISE. Study2. Acceptance criteria: EC50 [M], log10(EC50), CV(EC50) [%],

PC, NC. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 63Table 75.RISE. Study3. Acceptance criteria: EC50 [M], log10(EC50), CV(EC50) [%],

PC, NC. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 63Table 76.BDS. Study2. Acceptance criteria: EC50 [M], log10(EC50), CV(EC50) [%],

PC, NC. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 64Table 77.Citoxlab. Study2. Antagonist testing. Acceptance criteria: Inhibition factor,

Z-factor. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 70Table 78.Envigo. Study2A. Antagonist testing. Acceptance criteria: Inhibition factor,

Z-factor. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 70Table 79.Envigo. Study2B. Antagonist testing. Acceptance criteria: Inhibition factor,

Z-factor. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 70Table 80.RISE. Study2. Antagonist testing. Acceptance criteria: Inhibition factor,

Z-factor. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 71

323

Table 81.RISE. Study3. Antagonist testing. Acceptance criteria: Inhibition factor,Z-factor. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 71

Table 82.BDS. Study2. Antagonist testing. Acceptance criteria: Inhibition factor,Z-factor. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 72

Table 83.Citoxlab. Study2. Antagonist testing. Acceptance criteria: IC50 [M],log10(IC50), CV(IC50) [%], PC, NC, VC, R2 . . . . . . . . . . . . . . . . . . 72

Table 84.Envigo. Study2A. Antagonist testing. Acceptance criteria: IC50 [M], log10(IC50),CV(IC50) [%], PC, NC, VC, R2 . . . . . . . . . . . . . . . . . . . . . . . . . . 73

Table 85.Envigo. Study2B. Antagonist testing. Acceptance criteria: IC50 [M], log10(IC50),CV(IC50) [%], PC, NC, VC, R2 . . . . . . . . . . . . . . . . . . . . . . . . . . 73

Table 86.RISE. Study2. Antagonist testing. Acceptance criteria: IC50 [M], log10(IC50),CV(IC50) [%], PC, NC, VC, R2 . . . . . . . . . . . . . . . . . . . . . . . . . . 73

Table 87.RISE. Study3. Antagonist testing. Acceptance criteria: IC50 [M], log10(IC50),CV(IC50) [%], PC, NC, VC, R2 . . . . . . . . . . . . . . . . . . . . . . . . . . 74

Table 88.BDS. Study2. Antagonist testing. Acceptance criteria: IC50 [M], log10(IC50),CV(IC50) [%], PC, NC, VC, R2 . . . . . . . . . . . . . . . . . . . . . . . . . . 74

Table 89.Test item 1. Relative induction Yc with sample std in brackets(N=3). Es-timated log10(EC50) and log10(PC10) values. Highlighted in green valueswhere Yc ≥ 10. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 78











324


















325


















326



Table 136.Test item 1. Relative induction Yc with sample std in brackets(N=3) in threeaccepted runs, R2 statistics, estimated log10(IC50) and log10(PC80) valuesand interpolated values for response at the concentration c8/2 (where ap-propriate). Highlighted in green values where Yc ≤ 80. . . . . . . . . . . . . 167

Table 137.Test item 1. Specificity control Sc. Relative induction with sample std inbrackets(N=3). Highlighted in green values where Sn

c ≤ 80 where Snc = Sc/Sc1.168
















327




Table 151.Test item 10. Relative induction Yc with sample std in brackets(N=3) inthree accepted runs, R2 statistics, estimated log10(IC50) and log10(PC80)values and interpolated values for response at the concentration c8/2 (whereappropriate). Highlighted in green values where Yc ≤ 80. . . . . . . . . . . . 215

















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statistical report of the ar-calux validation study

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