app203766 revystar® fungicide...hazard classification of revystar® fungicide 2.4. the hazard...

SCIENCE MEMO

APP203766 – Revystar® Fungicide

DECEMBER 2019

Project team

Application lead:

Toxicologist:

Ecotoxicologist:

Peer-reviewer:

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Science memo for application to import or manufacture Revystar® Fungicide for release (APP203766)

DECEMBER 2019

Executive Summary

The applicant BASF New Zealand Limited has submitted an application on 29 November 2018 to import or

manufacture Revystar® Fungicide for release. It was given Application Number APP203766 and was

formally received on 01 July 2019 as a Category C application.

The active ingredient contained in Revystar® Fungicide, mefentrifluconazole, has not previously been

approved in New Zealand for use as a fungicide. It has been approved internationally for this use pattern in

Europe, Australia, and the USA. The active ingredient fluxapyroxad has been approved in New Zealand as a

fungicide for cereals.

Mefentrifluconazole is of very low acute toxicity in mammals by oral, dermal, inhalation routes and should not

be classified. It is not a skin or eye irritant. However, mefentrifluconazole was found to be a contact

sensitiser and should be classified as 6.5B. It was found not to be genotoxic, carcinogenic, and does not

cause reproductive or developmental toxicity, or target organ toxicity. Mefentrifluconazole is very ecotoxic in

the aquatic environment (9.1A) and harmful to terrestrial vertebrates (9.3C), it is not ecotoxic in the soil

environment or to terrestrial invertebrates

The proposed toxicity classification of Revystar® Fungicide is: 6.1D acute toxicity (oral and inhalation), 6.3A,

6.4B, and 6.5B for skin and eye irritation, and contact sensitisation, respectively. It is classified 6.9B specific

organ toxicity due to fluxapyroxad.

The proposed ecotoxicity hazard classification of Revystar® Fungicide is: 9.1B (ecotoxic in the aquatic

environment) and 9.3C (harmful to terrestrial vertebrates). The EPA staff classification of Revystar®

Fungicide differed from that of the applicant in that they did not classify it for toxicity to terrestrial vertebrates.

Mefentrifluconazole is considered highly persistent in both the aquatic environment and soil environment

according to Annex D of the HSNO Act . Mefentrifluconazole is considered slightly mobile to immobile in soil

according to the McCall classification system . Mefentrifluconazole is considered to have a low potential for

bioaccumulation.

It is considered that there is potential for significant exposure to people and the environment during the use

phase of the lifecycle of Revystar® Fungicide. As such, quantitative risk assessments have been undertaken

to understand the likely exposures to the substance under the use conditions proposed by the applicant,

using the endpoint data available and the standard risk assessment methodologies used by the EPA (EPA

2018).

It is considered that the risks to human health from the proposed use of Revystar® Fungicide are acceptable

without the use of Personal Protective Equipment (PPE), application of re-entry intervals, or enforcement of

no-spray buffer zones to protect bystanders.

It is considered that the risks to the environment from the proposed use of Revystar® Fungicide are

acceptable with the proposed controls

A set of controls have been proposed for Revystar® Fungicide, and are detailed under section 6.

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Table of Contents

APP203766 – Revystar® Fungicide ..................................................................................................... 1

Executive Summary .............................................................................................................................. 2

Table of Contents .................................................................................................................................. 3

1. Introduction/Background ........................................................................................................... 7

2. Hazardous properties ................................................................................................................. 9

Hazard classification of mefentrifluconazole ................................................................................. 9

Hazard classification of Revystar® Fungicide ............................................................................... 9

Identification of components of concern (CMRs, vPBTs etc) ...................................................... 10

3. Risk assessment context ......................................................................................................... 10

4. Human health risk assessment................................................................................................ 11

5. Environmental risk assessment .............................................................................................. 11

6. Proposed controls ..................................................................................................................... 13

Appendix A: Identity of the active ingredient, use pattern and mode of action ........................... 15

Identity of the active ingredient and metabolites ......................................................................... 15

Regulatory status ........................................................................................................................ 16

Table 5: List of intended uses for Revystar® Fungicide ............................................................. 18

Appendix B: Physico-chemical properties of Revystar® Fungicide .............................................. 20

Appendix C: Mammalian toxicology .................................................................................................. 21

Executive summaries and list of endpoints for Revystar® Fungicide ......................................... 21

Executive summaries and list of endpoints for mefentrifluconazole ........................................... 22

General conclusion about mefentrifluconazole ........................................................................... 26

Appendix D: Environmental fate ........................................................................................................ 28

Executive summaries and list of endpoints ................................................................................. 28

Residues relevant to the environment ......................................................................................... 28

Degradation and fate of mefentrifluconazole in aquatic environments ....................................... 30

Degradation and fate of mefentrifluconazole in soil .................................................................... 31

General conclusion about environmental fate ............................................................................. 33

Appendix E: Ecotoxicity ..................................................................................................................... 35

Executive summaries and list of endpoints ................................................................................. 35

Aquatic toxicity ............................................................................................................................ 35

Metabolites ........................................................................................................................ 43

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Uncertainties and data gaps ............................................................................................. 43

General conclusion about aquatic toxicity......................................................................... 43

Soil toxicity................................................................................................................................... 44


General conclusion about soil toxicity ............................................................................... 47

Terrestrial vertebrate toxicity ....................................................................................................... 47


Ecotoxicity to bees and other terrestrial invertebrates ................................................................ 48


General conclusion about ecotoxicity to bees and terrestrial invertebrate toxicity 50

Appendix F: Hazard classification of mefentrifluconazole and Revystar® Fungicide ................. 51

Appendix G: Human health risk assessment ................................................................................... 56

Quantitative risk assessment ...................................................................................................... 56

Input values for the human health risk assessment .......................................................... 56

Operator exposure assessment ........................................................................................ 57

Re-entry worker exposure assessment ............................................................................ 59

Quantitative bystander risk assessment ........................................................................... 59

Conclusions of the human health risk assessment ........................................................... 60

Appendix H: Environmental risk assessment .................................................................................. 61

Mixture toxicity ............................................................................................................................. 61

Aquatic risk assessment .............................................................................................................. 64

Calculation of expected environmental concentrations .................................................... 64

Output from the GENEEC2 model .................................................................................... 65

Calculated risk quotients ................................................................................................... 67

Refinement of the aquatic risk assessment ...................................................................... 68

Conclusions of the aquatic risk assessment ..................................................................... 70

Groundwater risk assessment ..................................................................................................... 70

Conclusions of the groundwater risk assessment ............................................................ 71

Sediment risk assessment .......................................................................................................... 71

Terrestrial risk assessment ......................................................................................................... 72

Soil macro-organisms ....................................................................................................... 72

Soil accumulation .............................................................................................................. 75

Conclusions of the soil organism risk assessment ........................................................... 76

Non-target plant risk assessment ................................................................................................ 77

Conclusion for non-target plant risk assessment .............................................................. 77

Bird risk assessment ................................................................................................................... 78

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Screening assessment ...................................................................................................... 78

Calculation of TERs .......................................................................................................... 78

Conclusions of the bird screening risk assessment .......................................................... 79

Tier 1 assessment ............................................................................................................. 79

Secondary poisoning ......................................................................................................... 80

Conclusions for bird risk assessment ............................................................................... 80

Pollinator risk assessment ........................................................................................................... 80

Conclusions of the pollinator risk assessment .................................................................. 81

Non-target arthropod risk assessment ........................................................................................ 81

Conclusion for non-target arthropod risk assessments .................................................... 82

Conclusions of the ecological risk assessment ........................................................................... 83

Aquatic risk assessment ................................................................................................... 83

Soil organism risk assessment ......................................................................................... 84

Non-target plant risk assessment ..................................................................................... 84

Bird risk assessment ......................................................................................................... 84

Pollinator risk assessment ................................................................................................ 84

Non-target arthropod risk assessments ............................................................................ 84

Appendix I: Proposed controls .......................................................................................................... 86

Prescribed controls ...................................................................................................................... 86

Exposure thresholds .................................................................................................................... 86

Impurity limits............................................................................................................................... 87

Ecotoxicity controls ...................................................................................................................... 87

Application restrictions ................................................................................................................ 87

Application method ...................................................................................................................... 87

Buffer zones ................................................................................................................................ 88

Appendix J: Study summaries ........................................................................................................... 89

Toxicity study summaries ............................................................................................................ 89

Mammalian toxicology - Robust study summaries for Revystar® .................................... 89

Environmental fate studies ........................................................................................................ 101

Abiotic degradation ......................................................................................................... 101

Biological degradation – biodegradation in soil .............................................................. 102

Mobility in soil .................................................................................................................. 108

Bioconcentration/bioaccumulation studies ...................................................................... 110

Ecotoxicity study summaries ..................................................................................................... 113

Aquatic ecotoxicity of the active ingredient ............................................................................... 113

Short-term aquatic toxicity studies .................................................................................. 113

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Chronic toxicity to sediment-dwelling organisms ............................................................ 134

Aquatic ecotoxicity of metabolites of mefentrifluconazole .............................................. 135

Soil toxicity of the active ingredient ........................................................................................... 141

Toxicity to terrestrial plants ............................................................................................. 141

Terrestrial vertebrate toxicity of the active ingredient ..................................................... 145

Acute toxicity to birds (oral) ............................................................................................. 145

Acute toxicity to birds (dietary) ........................................................................................ 148

Chronic toxicity to birds (reproduction) ........................................................................... 150

Toxicity of the active ingredient to terrestrial invertebrates ............................................. 152

Acute toxicity to pollinators ............................................................................................. 152

Chronic toxicity to pollinators .......................................................................................... 156

Appendix K: Standard terms and abbreviations ............................................................................ 157

Appendix L: References ................................................................................................................... 160

Appendix M: Confidential Composition .......................................................................................... 161

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1. Introduction/Background

1.1. This application is to import or manufacture Revystar® Fungicide for release.

1.2. Revystar® Fungicide is intended to be used as fungicide to control various fungal diseases on wheat,

barley, oats, ryecorn, triticale, and ryegrass.

1.3. Revystar® Fungicide contains the active ingredients mefentrifluconazole at 100 g/L and fluxapyroxad

at 50 g/L, plus other components.

1.4. The active ingredient contained in Revystar® Fungicide, mefentrifluconazole, has not previously been

approved in New Zealand for use as a fungicide. It has been approved internationally for this use

pattern in Europe, Australia, and the USA. The active ingredient fluxapyroxad has been approved in

New Zealand as a fungicide for cereals.

1.5. The active ingredient fluxapyroxad, contained in Revystar® Fungicide has previously been approved

in New Zealand for use on cereal grains at a similar application rate (Adexar, application APP201884,

approval HSR100948).

1.6. More details about the use pattern of Revystar® Fungicide and the regulatory status of

mefentrifluconazole can be found in Appendix A.

1.7. It is considered that there is potential for significant exposure to people and the environment during

the use phase of the lifecycle of Revystar® Fungicide. As such, quantitative risk assessments have

been undertaken to understand the likely exposures to the substance under the use conditions

proposed by the applicant, using the endpoint data available and the standard risk assessment

methodologies used by the EPA (EPA 2018). Exposure modelling was only conducted on

mefentrifluconazole as modelling on fluxapyroxad was previously completed as noted in 1.5.

Fungicide Full context related to the risk assessment of Revystar® Fungicide is given in section 3.

1.8. Unless otherwise stated, all endpoint data summarised were fully compliant with the relevant

international test methods. For full details of testing undertaken, reference should be made to the

relevant sections of the overseas review [(EFSA 2018) , (EC 2017)]. The applicant has confirmed they

have access to the studies conducted with mefentrifluconazole contained in Revystar® Fungicide. The

original study reports have been provided.

1.9. Physical and Chemical properties of Revystar® Fungicide can be found in Appendix B.

1.10. Mammalian toxicological properties Revystar® Fungicide and mefentrifluconazole have been reported

in Appendix C.

1.11. Environmental Fate properties of mefentrifluconazole have been reported in Appendix D.

1.12. Ecotoxicological properties of Revystar® Fungicide and mefentrifluconazole have been reported in

Appendix E.

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1.13. Hazard properties and classification determination of Revystar® Fungicide and mefentrifluconazole

derived from their properties can be found under Section 2. Hazardous properties and Appendix F.

1.14. Mammalian toxicological data have subsequently been used to generate human health risk

assessment and this is detailed in Appendix G.

1.15. Environmental Fate, Ecotoxicological and other relevant data have subsequently been used to

generate environmental risk assessment and this is detailed in Appendix H.

1.16. Relevant study summaries can be found in Appendix J.

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2. Hazardous properties

Hazard classification of mefentrifluconazole

2.1. The hazard classification proposed for mefentrifluconazole is outlined in Table 1.

Table 1: Proposed classification for mefentrifluconazole

Hazard endpoint Classification

Contact sensitisation 6.5B

Aquatic ecotoxicity 9.1A

Toxicity to terrestrial vertebrates 9.3C

2.2. Mefentrifluconazole is of very low acute toxicity in mammals by oral, dermal, inhalation routes and

should not be classified. It is not a skin or eye irritant. However, mefentrifluconazole was found to be a

contact sensitiser and should be classified as 6.5B. It was found not to be genotoxic, carcinogenic,

and does not cause reproductive or developmental toxicity, or target organ toxicity.

2.3. Mefentrifluconazole is very ecotoxic in the aquatic environment (9.1A) and harmful to terrestrial

vertebrates (9.3C), it is not ecotoxic in the soil environment or to terrestrial invertebrates.

Hazard classification of Revystar® Fungicide

2.4. The hazard classifications of Revystar® Fungicide determined by the EPA staff are 6.1D for both

acute oral and inhalation toxicity. The substance is irritating to both the skin and eyes, and is a weak

contact sensitiser and is respectively classified 6.3A, 6.4B, and 6.5B for these hazards (Table 2). The

hazard classifications of Revystar® Fungicide were determined based on the information provided by

the applicant (including toxicity and ecotoxicity studies), information on the individual components of

Revystar® Fungicide, mixture rules and other available information (EC 2017). Table 4 in Appendix F

shows the method used for classification and indicates the main component that contributes to each

hazard classification.

Table 2: Hazard classification of Revystar® Fungicide

Hazard EPA classification

Acute toxicity (oral) 6.1D

Acute toxicity (inhalation) 6.1D

Skin irritancy/corrosivity 6.3A

Eye irritancy/corrosivity 6.4A

Contact sensitisation 6.5B

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Hazard EPA classification

Target organ or systemic (oral) 6.9B

Aquatic ecotoxicity 9.1B

Terrestrial vertebrate ecotoxicity 9.3C

2.5. Mammalian toxicity studies with Revystar® Fungicide indicate that the substance is of low acute

toxicity and should be classified 6.1D for acute oral and inhalation toxicity and is not classifiable for

acute dermal toxicity. The substance is irritating to both the skin and eyes, and is a contact sensitiser

(albeit weak) and is respectively classified 6.3A, 6.4B, and 6.5B for these hazards. A 6.9B

classification for target organ specific toxicity is present due to the fluxapyroxad active ingredient.

2.6. The proposed ecotoxicity hazard classification of Revystar® Fungicide is: 9.1B (ecotoxic in the aquatic

environment) and 9.3C (harmful to terrestrial vertebrates). The EPA staff classification of Revystar®

Fungicide differed from that of the applicant in that the applicant did not classify it for toxicity to

terrestrial vertebrates.

Identification of components of concern (CMRs, vPBTs etc)

The following component(s) that are present in Revystar® Fungicide were identified to be of concern as they

are known / suspected to be a CMR / vPBT etc:

a) N,N-dimethylformamide (DMF; 68-12-2); reproductive hazard (6.8A): 0.5 g/kg

b) Toluene (108-88-3); reproductive hazard (6.8B): 1 g/kg

c) 1,2,4-(1H)-triazole (288-88-0); reproductive hazard (6.8A): 1 g/kg

These are considered relevant impurities and the maximum concentrations are expressed in relation to the

content of mefentrifluconazole.

3. Risk assessment context

3.1. It is considered that there is potential for significant exposure to people and the environment during

the use phase of the lifecycle of Revystar® Fungicide. As such, quantitative risk assessments have

been undertaken to understand the likely exposures to the substance under the use conditions

proposed by the applicant, using the endpoint data available and the standard risk assessment

methodologies used by the EPA (EPA 2018).

3.2. During the importation, manufacture, transportation, storage and disposal of this substance, it is

estimated that the proposed controls and other legislative requirements will sufficiently mitigate risks to

a negligible level. This assessment takes into account the existing EPA Notices around packaging,

identification and disposal of hazardous substances. In addition, the Land Transport Rule 45001, Civil

Aviation Act 1990, Maritime Transport Act 1994 and New Zealand’s Health and Safety at Work (HSW)

requirements all have provisions for the safe management of hazardous substances.

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4. Human health risk assessment

4.1. The risks (from the use of mefentrifluconazole are considered as a proxy for Revystar® Fungicide) on

users and operators of the substance, re-entry workers and bystanders. Full details can be found in

Appendix G: Human health risk assessment.

4.2. Operator Exposure:

Predicted operator exposures to mefentrifluconazole are below the Acceptable Operator Exposure

Level (AOEL) for each use pattern, even without the use of personal protective equipment (PPE).

Therefore operator exposures are not expected to result in adverse health effects

Although the quantitative risk assessment indicates that PPE is not required to ensure that exposures

are below the AOEL, the requirements under HSW (HS), and in particular Regulations 13.7 and 13.8,

state that personal protective equipment is to be used to minimise risks to the health and safety of

workers.

4.3. Worker re-entry:

Predicted exposures to mefentrifluconazole for workers re-entering and working in areas where

Revystar® Fungicide has been applied are below the AOEL. No re-entry intervals are necessary

4.4. Bystanders:

Estimated bystander exposure from spray drift after application of Revystar® Fungicide to cereals is

below the AOEL. No buffer zone is required to protect bystanders

4.5. Impurities:

Three impurities of toxicological concern were identified by the EPA (Appendix A). The Certificate of

Analysis (CoA) indicates all are well below the maximum allowable levels.

4.6. Overall human health conclusion:

It is considered that the risks to human health from the proposed use of Revystar® Fungicide are

acceptable without the use of Personal Protective Equipment (PPE), application of re-entry intervals,

or enforcement of no-spray buffer zones to protect bystanders.

5. Environmental risk assessment

5.1. No product-specific ecotoxicity data is available for the formulated substance Revystar® Fungicide

(BAS 752 00 F). The applicant has performed a mixture toxicity assessment, which establishes which

active ingredient mostly contributes to the toxicity for each area of the risk assessment, assuming

additivity, following EFSA Guidance (EFSA 2013). This is based on the individual toxicity endpoints for

each of the active ingredients fluxapyroxad and mefentrifluconazole, and their relative contribution to

the formulation.

5.2. Following publication of the US EPA’s Environmental Fate and Ecological Risk Assessment for

mefentrifluconazole (US EPA 2019) and the Canadian Pest Management Regulatory Agency’s

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(PMRA) Proposed Registration Decision for mefentrifluconazole and related use end products (PMRA

2019), it is apparent that ecotoxicity formulation data are available for other mefentrifluconazole-

containing formulations. The EPA has therefore performed a mixture toxicity assessment, also

following the EFSA guidance (EFSA 2013) based on this information. Full details can be found in

Appendix H.

5.3. Since the active ingredient fluxapyroxad has already been approved in New Zealand in other

formulations for similar uses at similar rates, this environmental risk assessment focusses only on the

active ingredient mefentrifluconazole, which is new to New Zealand. Full details can be found in

Appendix H.

5.4. Aquatic environment:

Estimated Environmental Concentrations (EECs) of mefentrifluconazole applied as the formulated

product Revystar resulted in calculated Risk Quotients (RQs) above the Level Of Concern (LOC) for

the aquatic environment. To mitigate these risks, it is proposed to apply controls to reduce spray-drift

into the aquatic environment.

5.5. Groundwater:

For mefentrifluconazole and its metabolite M750F001 (1,2,4-triazole) the predicted concentration in

groundwater is below the 0.1 µg/L trigger level set by the European regulators. Therefore, risks to

groundwater are considered below the level of concern

5.6. Sediment:

The risk quotients for sediment-dwelling organisms following both ground-based and aerial application

were both identified as potentially being above the level of concern (LOC = 1).

Only one chronic endpoint, which is not an absolute value, was available for sediment-dwelling

organisms, and the risk assessment was performed with this value (28-day NOEC of ≥1.158 mg ai/kg

for Chironomus riparius). The No Observed Effect Concentration (NOEC) determined in this case was

the highest concentration tested, and no significant effects were observed at this concentration. If a

higher concentration had been tested, the NOEC could potentially be higher, thus resulting in a lower

risk.

Using a weight-of-evidence approach, given the uncertainty in the determined NOEC value, the fact

that the active ingredient mefentrifluconazole is a fungicide (and no risks were identified for pollinators

or non-target arthropods), and other regulators (EFSA 2018) concluded that risks to sediment-dwelling

organisms were low, risks to sediment-dwelling organisms are considered to be low.

5.7. Soil organisms:

Acute TERs for soil organisms for the active ingredient mefentrifluconazole following application of

Revystar® Fungicide are below the LOC for non-threatened and threatened species, both in-field and

off-field.

Chronic TERs for soil organisms for the active ingredient mefentrifluconazole following application of

Revystar® Fungicide are above the LOC for threatened species in-field. TERs were below the LOC for

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non-threatened species in-field, as well as for off-field for both non-threatened and threatened species.

Due to the risk identified for threatened earthworm species in-field, chronic TER values were refined,

taking into account interception by the crop (80%). The chronic TER for threatened species in-field is

still above the LOC however. Further evaluation indicated that threatened species are unlikely present

in the application areas of Revystar® Fungicide as a result the risk is considered to be below the LOC.

In regard to soil accumulation, the acute TER values were below the level of concern for both non-

threatened and threatened species. At Tier I (assuming 0% crop interception), chronic risks to

earthworms were above the LOC for both non-threatened and threatened species.

At Tier II (assuming 80% crop interception corresponding to growth stage BBCH 30-39 as described

above, is the earliest growth stage that the substance will be applied), chronic risks were identified

only for threatened species, which are considered unlikely to be exposed to Revystar® Fungicide in-

field.

5.8. Non-target Plants:

Risk Quotients (RQs) to non-target plants calculated for mefentrifluconazole when applied to cereals

as the formulated product Revystar® Fungicide are below the level of concern

5.9. Birds:

TER values for birds calculated for the active ingredient mefentrifluconazole when applied to cereals

as the formulated product Revystar® Fungicide are below the LOC for acute risks, and any risks are

negligible. In the reproductive screening assessment, the TER values indicate a chronic risk above the

LOC to non-threatened and threatened bird species. After the Tier I risk assessment, risks to non-

threatened and threatened species of birds are considered below the LOC. The risks from secondary

poisoning is considered to be low

5.10. Pollinators:

The risks to pollinators are below the LOC and any risks are negligible

5.11. Non-target Arthropods:

Risks to non-target arthropods are below the LOC for both off-field and in-field.

5.12. Overall Ecological risk assessment conclusion:


acceptable with the proposed controls

6. Proposed controls

6.1. More details about proposed controls are available in Appendix I.

Application rate

6.2. Maximum application rate of 150 g mefentrifluconazole/ha, maximum two applications per year with a

minimum interval between applications of 21 days.

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6.3. Maximum application rate of 75 g fluxapyroxad/ha, maximum two applications per year with a

minimum interval between applications of 21 days.

Maximum impurity limit

6.4. Impurity limits for mefentrifluconazole have been identified by the EU. The EPA has proposed the

following maximum impurity limits: N,N-dimethylformamide (DMF; 68-12-2): 0.5 g/kg; toluene (108-88-

3): 1 g/kg; 1,2,4-(1H)-triazole (288-88-0): 1 g/kg

Application method

6.5. Revystar must not be applied when wind speeds are less than 3 km/hr or more than 20 km/hr as

measured at the application site.

6.6. Apply with ground-based equipment and minimum medium droplets, as defined by the American

Society of Agricultural and Biological Engineers ASABE Standard (S572) or the British Crop

Production Council guideline. This information should be required on the label so that users are aware

of this control.

For aerial application, use minimum coarse droplets, as defined by the American Society of

Agricultural and Biological Engineers ASABE Standard (S572) or the British Crop Production Council

guideline. This information should be required on the label so that users are aware of this control.

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Appendix A: Identity of the active ingredient, use pattern and mode of action

Identity of the active ingredient and metabolites

As this is the first full application under Part 5 of the Hazardous Substances and New Organisms (HSNO)

Act 1996 considered for mefentrifluconazole, general data derived from the application form and from

Barbieri, R.F. (2018); Volume 1: Chemistry & Manufacture BASF Doc ID: 2018/NZ105 are provided in Table

3.

Table 3: Identification of mefentrifluconazole

IUPAC name (2RS)-2-[4-(4-chlorophenoxy)-2-(trifluoromethyl)phenyl]-1-(1H-

1,2,4-triazol-1-yl)propan-2-ol

CAS name alpha-[4-(4-chlorophenoxy)-2-(trifluoromethyl)phenyl]-alpha-

methyl-1H-1,2,4-triazole-1-ethanol

Molecular formula C18H15ClF3N3O2

CAS Number 1417782-03-6

Molecular weight 397.8 g/mol

Structural formula

Purity ≥970 g/kg

Significant

impurities/additives

(% concentration)

2-[4-(4-chlorophenoxy)-2-(trifluoromethyl)phenyl]-1-(4H-1,2,4-

triazol-4-yl)propan-2-ol; (5886575) : ≤23 g/kg

2-[4-(4-chlorophenoxy)-2-(trifluoromethyl)phenyl]-1-(1H-1,2,4-

triazol-1-yl)butan-2-ol; 5832500: ≤ 10 g/kg

1-(4-chlorophenoxy)-3-(trifluoromethyl)benzene; 5958976: ≤ 2.0

g/kg

Other international

classification & labelling

None identified

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Regulatory status

The regulatory history of mefentrifluconazole is summarised in Table 4 below.

Table 4: regulatory status of mefentrifluconazole and fluxapyroxad

Active ingredient

name

Regulatory history in

New Zealand

International regulatory history

(Australia, Canada, Europe,

Japan, USA)

mefentrifluconazole New to Zealand Europe, Australia, and USA

fluxapyroxad Approved Approved in EU, USA, Canada,

Australia

The active ingredient contained in Revystar® Fungicide, mefentrifluconazole, has not previously been

approved in New Zealand for use as a fungicide. It has been approved internationally for this use pattern in

Europe, Australia, and the USA. The active ingredient fluxapyroxad has been approved in New Zealand as a

fungicide for cereals.

The active ingredient fluxapyroxad, contained in Revystar® Fungicide has previously been approved in New

Zealand for use on cereal grains at a similar application rate (Adexar, application APP201884, approval

HSR100948).

Impurities and or restrictions on purity or composition

Impurity limits for mefentrifluconazole have been identified by the EU (EC 2019)These are:

N,N-dimethylformamide (DMF; 68-12-2): 0.5 g/kg

toluene (108-88-3): 1 g/kg

1,2,4-(1H)-triazole (288-88-0): 1 g/kg

Use pattern and mode of action

Use pattern

Revystar® Fungicide is an emulsifiable concentrate which is diluted in water (150-300 litres of water per

hectare). The applicant seeks to have Revystar® Fungicide approved for ground based and aerial

application.

Application will be at the rate of 1 – 1.5 L of product per hectare (L/ha) which is equivalent to 0.100 – 0.150

kg/ha of mefentrifluconazole and 0.050 - 0.075 kg/ha of fluxapyroxad, with a maximum frequency of 2

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applications per year a minimum of 21 days apart. More details on the intended uses for Revystar®

Fungicide are given in Table 5.

Mode of action

The active mefentrifluconazole is a fungicide belonging to the group of the sterol biosynthesis inhibitors (SBI,

mode of action class G – FRAC). Within the SBIs, it belongs to the sub group of demethylation inhibitor (DMI,

G1) and the chemical group of triazoles. The primary mode of action of DMIs is the blocking of ergosterol

biosynthesis through inhibition of cytochrome P450 sterol 14α-demethylase (CYP51). The depletion of

ergosterol and accumulation of non-functional 14α-methyl sterols results in inhibition of growth and cell

membrane disruption.

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Table 5: List of intended uses for Revystar® Fungicide

Crop

and/or

situation

(a)

Use

patt

ern

(b)

Pests or

group of

pests

controlled

(c)

Mixture Application Application rate per treatment

PHI

Remarks

(l) Type

(d-f)

Conc of ai

(g)

Method

and kind

(h-i)

Growth

stage &

season (j)

Num

ber

Min

max

(k)

Interval

between

applicatio

ns – days

(minimum)

kg ai/hL

min max

water

L/ha

min max

kg ai/ha

max

wheat,

barley,

oats,

ryecorn

triticale

and grass

seed

(ryegrass)

F foliar fungi EC

mefentriflu

conazole:

100 g/L

fluxapyrox

ad: 50 g/L

High

volume

spraying

(boom

spray or

aerial

application

Up to end

of

flowering

(Zadox GS

69)

spring/sum

mer

1 - 2 21 days

mefentrifluconaz

ole: 0.033 –

0.10

fluxapyroxad:

0.0167 – 0.050

150 –

300

ground,

60 air

mefentriflu

conazole:

0.10 –

0.150

fluxapyrox

ad: 0.05 –

0.075

Cereal

feed: 28

days

Cereal

grain: 42

days

Rye

grass

seed

crops: 14

days

NA

a Where relevant, the use situation should be described (eg fumigation of soil) b Outdoor or field use (F), glasshouse application (G) or indoor application (I). c eg biting and sucking insects, soil borne insects, foliar fungi, weeds d eg wettable powder (WP), emulsifiable concentrate (EC), granule (GR) e CropLife international, 2008. Technical Monograph no 2, 6th edition. Catalogue of pesticide formulation types and international coding system f All abbreviations used must be explained

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g g/kg or g/l or others h Method, eg high volume spraying, low volume spraying, spreading, dusting, drench, aerial, etc i Kind, eg overall, broadcast, aerial spraying, row, individual plant, between the plant - type of equipment used must be indicated. If spraying include droplet size spectrum j growth stage at last treatment (BBCH Monograph, Growth Stages of Plants, 1997, Blackwell (ISBN 3-8263-3152-4) , including where relevant, information on season at time of application k Indicate the minimum and maximum number of application possible under practical conditions of use l Remarks may include: Extent of use/economic importance/restrictions

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Appendix B: Physico-chemical properties of Revystar® Fungicide

The physico-chemical properties of Revystar® Fungicide are listed in Table 6.

Table 6: Physical and chemical properties of Revystar® Fungicide

Property Value Reference

Colour Dark yellow Barbieri, R.F. (2018); Volume 1:

Chemistry & Manufacture BASF Doc

ID: 2018/NZ105 and the SDS for

Revystar XL

Odour Mild, aromatic

Physical state Liquid

pH 5-7

Freezing point < -20°C

Flash point 112°C

Flammability Not highly flammable

Ignition temperature 380°C

Vapour pressure ~1 hPa (15°C)

Viscosity ~76 mPa.s (20°C, 100 1/s)

~32 mPa.s (40°C, 100 1/s)

Density ~1.02 g/cm3 (20°C)

Water Solubility (20°C) Emulsifiable

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Appendix C: Mammalian toxicology

Unless otherwise noted, all studies were conducted according to GLP and were fully compliant with the

requirements of the international test guidelines followed. Two in vitro studies assessing skin and eye

irritation were not summarised as they were only considered to be supportive in nature and did not impact

the classification.

The only data summarised in this memo are that for the new active, mefentrifluconazole, and the substance

Revystar. The other active ingredient in the substance, fluxapyroxad, has been previously approved for use

in New Zealand (HSR100948 and others).

Executive summaries and list of endpoints for Revystar® Fungicide

The mammalian toxicology data for Revystar® Fungicide are summarised in Table 7.

Table 7: Summary of mammalian toxicology data for Revystar® Fungicide

Endpoint

(Test Guideline)

Klimisch

score Result

HSNO

Classification Reference

Acute oral toxicity

(OECD 423; Commission

Regulation (EC) No

440/2008; US EPA OPPTS

870.1100)

1 LD50: 300 - 2000

mg/kg bw 6.1D

Appendix J; Table 56;

2014/1170783

Acute dermal toxicity


Regulation (EC) No


870.1200)

1 LD50: >5000

mg/kg bw No


2014/1170784

Acute inhalation toxicity


Regulation (EC) No

1907/2006 and 440/2008; US

EPA OPPTS 870.1300)

1 LC50: 1.9 - 5.1

mg/L 6.1D


2014/1132774

Acute toxicity (aspiration

hazard) 1

Viscosity:

~76 mPa.s (20°C,

100 1/s)

~32 mPa.s (40°C,

100 1/s)

No

Appendix B; Table 6;

2018/NZ105 and the

SDS for Revystar XL

Skin irritation/corrosion


Regulation (EC) No

1

Irritating

Mean score -

Erythema: 3.0

Oedema: 1.6

6.3A Appendix J; Table 59;

2014/1170785

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Endpoint

(Test Guideline)

Klimisch

score Result

HSNO

Classification Reference


870.2500)

Eye irritation/corrosion


Regulation (EC) No


870.2400)

1

Irritating

Mean Draize

Score -

Cornea

-Opacity: 1.0

Conjunctiva

-Redness: 1.6

-Chemosis: 1.1

Iris: 0.6

6.4A Appendix J; Table 60;

2014/1170786

Contact sensitisation


Regulation (EC) No.

440/2008, B.42)

1

Sensitising

SI at 25% was

4.06; EC3: 19.6%

6.5B (SI >3) Appendix J; Table 61;

2014/1170787

Executive summaries and list of endpoints for mefentrifluconazole

All data for mefentrifluconazole were sourced from the EU Draft Assessment Report [DAR (EC 2017)

Volume 3 – B.6 (AS)] and from study reports submitted from the applicant.

Acute toxicity, skin and eye irritation, contact sensitisation and genotoxicity data for mefentrifluconazole are

summarised in Table 8.

Table 8: Summary of acute toxicity, irritation, sensitisation and genotoxicity data for

mefentrifluconazole (BAS 750F)

Endpoint

(Test Guideline) Klimisch score Result Classification Reference

Acute oral toxicity

(OECD 423; US EPA

OPPTS 870.1100; EC No

440/2008)

1 LD50: >2000

mg/kg bw No

EC DAR (EC 2017)

/1149656

Acute dermal toxicity

(OECD 402; US EPA


440 / 2008)

1 LD50: >5000

mg/kg bw No

EC DAR (EC 2017)

/1149657

Acute inhalation toxicity 1 LC50: >5.3 mg/L No EC DAR (EC 2017)

/1127433

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Endpoint


(OECD 403; US EPA


440/2008, B.2)

Skin irritation/corrosion

(OECD 404; US EPA


440/2008)

1

Non-irritating

Mean score -

Erythema: 0.0

Oedema: 0.0

No EC DAR (EC 2017)

1150122

Eye irritation/corrosion

(OECD 405; US EPA


440/2008)

1

Non-irritating

Mean Draize

Score -

Cornea

-Opacity: 0.0

Conjunctiva

-Redness: 0.4

-Chemosis: 0.0

Iris: 0.0

No EC DAR (EC 2017)

/1150121

Contact sensitisation

(OECD 406; US EPA


440/2008, B.6)

1

Sensitisation

(positive

reaction in 6/10

animals)

6.5B

EC DAR (EC 2017)

/1150123

Mutagenicity (3 studies): In

Vitro

Reverse mutation assay in

bacteria (OECD 471; US

EPA OPPTS 870.5100; EC

No. 440/2008, B.13/B.14)

Forward mutation assay in

mammalian cells (OECD

476; US EPA OPPTS

870.5300; EC No. 440/2008,

B.17)

Cytogenicity in mammalian

cells (OECD 487; EC No.

640/2012, B.49)

1 Negative (±S9)

No

EC DAR (EC 2017)

2014/1128030

2015/1116956

2015/1112683

2015/1101908

2013/1375108

2015/1101907

Mutagenicity: In Vivo

Micronucleus test 1 Negative

EC DAR (EC 2017)

/1043159

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Endpoint


(OECD 474; US EPA

OPPTS 870.5395; EC No.

440/2008, B.12)

Results of the repeated dose toxicity studies with mefentrifluconazole are summarised in Table 9.

Table 9: Summary of repeated dose studies with mefentrifluconazole (BAS 750F)

Study type

NOAEL

(mg/kg

bw/day)

LOAEL

(mg/kg

bw/day

Key effect Reference

28-day dermal study: rats

(OECD 410; US EPA


440/2008)

1000 NA No effects observed at the

highest dose

EC DAR (EC

2017)

/1170751

90-day oral toxicity: rats

(OECD 408; US EPA


440/2008)

76 males (M) /

91 females (F) 256 / 314

Decreased bw and bw gain,

increased liver wt, impairment

of liver function (clinical

chemistry changes)

EC DAR (EC

2017)

/1198721

90-day oral toxicity: mice

(OECD 408; US EPA


440/2008)

11 M / 15 F 58 / 67 Decreased bw gain, increased

liver wt and cell hypertrophy

EC DAR (EC

2017)

/1046542

90-day oral toxicity: dogs

(OECD 409; US EPA


440/2008, B.27)

90 180

Decreased food intake and bw

gain, increased liver wt and

altered liver function (clinical

chemistry changes)

EC DAR (EC

2017)

/1000530

1-year oral toxicity: dogs

(OECD 452; US EPA

OCSPP 870.4100)

30 M / F 150 M / F


increased liver wt and altered

liver function (clinical

chemistry changes)

EC DAR (EC

2017)

/1000645

Number on

study report

2016/1273716

18-month dietary chronic

toxicity/carcinogenicity

study: mice

(OECD 451; US EPA

OPPTS 870.4200)

chronic: 3.5 M

/ 4.9 F

carc.: 36 M /

61.5 F

chronic: 36 /

62

carcinogenicity

: not

carcinogenic


increased relative liver wt, and

increased signs of

(pre)degeneration in liver cells

Not carcinogenic in mice

EC DAR (EC

2017)

1000532

Number on

study report

015/7007530

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Study type

NOAEL

(mg/kg

bw/day)

LOAEL

(mg/kg

bw/day

Key effect Reference

2-year chronic

toxicity/carcinogenicity: rat

(OECD 453; US EPA


440/2008, B.33)

chronic: 4 M /

38 F

carc.: 163 M /

302 F

chronic: 26 /

312

carc.: not

carcinogenic

Altered clinical chemistry

parameters in males

Not carcinogenic in mice

EC DAR (EC

2017)

/1000531

Developmental toxicity: rats

(OECD 414; US EPA


440/2008)

Maternal: 150

Offspring: 400

Maternal: 400

Offspring: NA

Maternal: decreased food

consumption, bw and bw gain

Offspring: No treatment related

effects

EC DAR (EC

2017)

/1170755

Developmental toxicity:

rabbits (OECD 414; US

EPA OPPTS 870.3700; EC

No 440/2008)

Maternal: 25

Offspring: 25 NA

Maternal: No treatment related

effects

Offspring: No treatment related

effects

EC DAR (EC

2017)

/1170757

2-generation reproductive

toxicity: rats

(OECD 416; US EPA

OPPTS 870.3800)

Parental: 25

Fertility: 200

Offspring: 75

Parental: 75

Fertility: No

effects at

highest dose

Offspring: 200

Parental: increases in some

clinical chemistry parameters

and liver wt

Fertility: No effects observed

Offspring: decrease in live

pups, pup wt, and wt gain

during lactation

EC DAR (EC

2017)

/1170754

Toxicokinetics and dermal absorption studies with mefentrifluconazole (BAS 750F) are summarised in Table

10.

Table 10: Summary of toxicokinetics and dermal absorption studies with mefentrifluconazole (BAS

750F)

Study type Results

Toxicokinetics

The absorption, distribution, excretion and metabolism of mefentrifluconazole in

mammals was investigated using a mixture of 14C-radiolabeled, 13C-labeled

mefentrifluconazole and non-labelled mefentrifluconazole.

The plasma kinetics of mefentrifluconazole in rats and mice demonstrated high

absorption (~85%) following oral administration, indicated potential enterohepatic

recirculation of the triazole moiety, and showed fast excretion and a more-or-less linear

correlation of the internal exposure to the oral dose.

The biliary excretion experiments confirmed that excretion was fast, more or less

complete and occurred to a major extent within three days after oral dosing in rats,

predominantly by the faecal route. There was no evidence of accumulation. The

distribution experiments demonstrated that mefentrifluconazole was rapidly and widely

distributed in rats after a single oral administration. The active substance was

extensively and rapidly metabolized resulting in rapid and extensive excretion (biliary

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and urinary routes). Results of a comparative in vitro metabolism study showed that the

metabolite patterns of 14C-BAS 750 F formed after incubation with human, rat and

mouse hepatocytes was quantitatively different but qualitatively the same in rat

hepatocytes compared with human cells. The study did not detect a unique human

metabolite and so the rat metabolism study is concluded to provide results that are

representative of human metabolism.

Dermal absorption

The results of an in vitro dermal absorption study conducted using radio-labelled BAS

750 F active in BAS 752 00 F showed 0.36 ± 0.26% and 2.82 ± 0.98% of the applied

dose of 14C-BAS 750 F was recovered as absorbed dose for the concentrate and as a

1:200 (v/v) spray dilution respectively.

General conclusion about mefentrifluconazole

Acute toxicity, irritation and sensitisation

Mefentrifluconazole exhibits very low acute toxicity by all exposure routes (oral, dermal, and inhalation) and

should not be classified. It is not a skin or eye irritant and should not be classified. It was shown to have the

potential be a contact sensitiser (albeit weak) and should be classified 6.5B.

Mutagenicity

Mefentrifluconazole showed no evidence of mutagenicity in several in vitro and in vivo assays.

Carcinogenicity

Mefentrifluconazole showed no evidence of carcinogenicity in either mice or rats.

Reproductive and developmental toxicity

Mefentrifluconazole showed no evidence of developmental toxicity in rats and rabbits, or reproductive toxicity

in rats in a 2-generation study.

Target organ toxicity

The primary target organ seen in rats, mice and dogs was the liver. All three species exhibited dose

responsive weight increase, hepatocellular hypertrophy, and ultimately morphological and degenerative

effects (mice only) and alterations in clinical chemistries. These effects, in general, were observed at dose

levels greater than 100 mg/kg bw (levels not requiring classification) except in mice (58/67 mg/kg bw

males/females). In mice, this dose was also approximately at the maximum tolerated dose (MTD). The effect

was not deemed of sufficient magnitude to classify as 6.9B, in the absence of similar findings in other animal

models.

Toxicokinetics and dermal absorption

The absorption, distribution, excretion and metabolism of mefentrifluconazole in mammals was investigated

using a mixture of 14C-radiolabeled, 13C-labeled mefentrifluconazole and non-labelled mefentrifluconazole.

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The plasma kinetics of mefentrifluconazole in rats and mice demonstrated high absorption (~85%) following

oral administration, indicated potential enterohepatic recirculation of the triazole moiety, and showed fast

excretion and a more-or-less linear correlation of the internal exposure to the oral dose.

The biliary excretion experiments confirmed that excretion was fast, more or less complete and occurred to a

major extent within three days after oral dosing in rats, predominantly by the faecal route. There was no

evidence of accumulation. The distribution experiments demonstrated that mefentrifluconazole was rapidly

and widely distributed in rats after a single oral administration. The active ingredient was extensively and

rapidly metabolized resulting in rapid and extensive excretion (biliary and urinary routes). Results of a

comparative in vitro metabolism study showed no unique human metabolites such that the rat metabolism

study is concluded to provide results that are representative of human metabolism.

The results of an in vitro dermal absorption study conducted using radio-labelled BAS 750 F active in BAS

752 00 F showed 0.36 ± 0.26 and 2.82 ± 0.98% of the applied dose of 14C-BAS 750 F were recovered as

absorbed dose for the concentrate and as a 1:200 (v/v) spray dilution respectively.

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Appendix D: Environmental fate

The active ingredient fluxapyroxad contained in Revystar® Fungicide has previously been approved in New


HSR100948 and others) and accordingly will not be reviewed or assessed in the context of this memo.

This section focusses only on the active ingredient mefentrifluconazole, which has not previously been

approved in New Zealand.

Executive summaries and list of endpoints

Unless otherwise noted, all studies were conducted according to GLP and were fully compliant with all

requirements of the standard international test methods used. All data for mefentrifluconazole and its

metabolites were sourced from the mefentrifluconazole DAR unless otherwise stated. Study summaries have

only been included in Appendix J where there are comments in regard to individual studies.

Residues relevant to the environment

In laboratory and field degradation studies in soil and water, four major metabolites of mefentrifluconazole

(ie, those found at ≥10% active radioactivity (AR) at any sample interval) were identified: M750F001 (1,2,4-

triazole), M750F005, M750F006 and M750F007. The major metabolites are listed in Table 11.

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Table 11: Major metabolites of mefentrifluconazole1

Metabolite

code Chemical name (IUPAC)

Molecular

weight (g/mol)

Chemical

formula

Max. % formed1

Reference

Soil Sediment Water

M750F001 1,2,4-triazole 69.1 C2H3N3 - 4.9 10.2 EC DAR (EC 2017): Doc ID

2015/1000941

M750F005

4-{4-[2-hydroxy-1-(1H-1,2,4-

triazol-1-yl)propan-2-yl]-3-

(trifluoromethyl)phenoxy}phenol

379.34 C18H16F3N3O3 - - 32.2

EC DAR (EC 2017): Doc ID

2015/7000233

M750F006

6-(4-chlorophenoxy)-3-methyl-3-

(1H-1,2,4-triazol-1-ylmethyl)-2-

benzofuran-1(3H)-one

355.78 C18H14ClN3O3 - - 30.7

M750F007

6-(4-hydroxyphenoxy)-3-methyl-3-

(1H-1,2,4-triazol-1-ylmethyl)-2-

benzofuran-1(3H)-one

337.34 C18H15N3O4 - - 43.9

1 Only major metabolites defined as per the HSNO Act (“metabolites formed in amounts of equal to or more than 10% of the applied amount of substance and any time-

point evaluated during the degradation studies in the appropriate compartment under consideration (soil or water)”) have been listed. Only the maximum percent formed

of each of these metabolites is reported in this table. Metabolites listed may have been identified in other compartments but since this is not relevant to the

environmental risk assessment as they did not meet the “major metabolite” criteria, the values were not reported here

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Four major metabolites, defined as per the HSNO Act as metabolites, formed in amounts of equal to or more

than 10% of the applied amount of substance and any time-point evaluated during the degradation studies in

the appropriate compartment under consideration (soil or water) were identified.

Three major metabolites were identified in the aqueous photolysis study: M750F005, M750F006 and

M750F007 (Doc ID 2015/7000233). Another major metabolite, M750F001 (1,2,4-triazole) was detected in the

aquatic aerobic metabolism study (15.1% in the whole system).

It is noted that M750F001 (1,2,4-triazole) has a higher chronic toxicity to earthworms than the parent

mefentrifluconazole (NOEC of 1.0 mg ai/kg vs. 4.0 mg ai/kg). M750F001 (1,2,4-triazole) was only formed at a

maximum of 5.2% in the soil metabolism study and then declined, and therefore does not meet the HSNO

Act threshold of 10% for identifying (and thus consideration of) a major metabolite. As such, M750F001

(1,2,4-triazole) is not considered a major metabolite in soil.

M750F001 1,2,4-triazole will be included in the groundwater risk assessment however, due to its higher

mobility in soil than parent mefentrifluconazole.

Degradation and fate of mefentrifluconazole in aquatic environments

Information on the degradation and fate of mefentrifluconazole in the aquatic environment is summarised in

Table 12. Information on bioaccumulation potential is listed in Table 13. Values highlighted in bold are used

in the quantitative risk assessment.

Table 12: Degradation and fate of mefentrifluconazole in aquatic environments

Test type Mefentrifluconazole Reference

Ready biodegradation Not readily biodegradable EC DAR (EC 2017): Doc ID

2014/1239574

Aqueous photolysis half-life (DT50) 2.3 days1


2015/7000233

Aerobic mineralisation in surface

water (DT50)

No significant degradation observed, no

DT50 values could be calculated (pelagic

test system, OECD 309)


2015/1186902

Degradation in aerobic

water/sediment (whole system DT50)

122 days and 213 days


2015/1000941

Water solubility at 20°C [mg/L] 0.81 (water) EC DAR (EC 2017); Doc ID

2013/1397136

Hydrolysis half-life (DT50) Stable at pH 4-9


2015/1046919

1 Note that the aqueous photolysis value is based on continuous radiation. The actual direct photodegradation rate at

different temperatures and for different latitudes does not appear to have been calculated.

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Table 13: Bioaccumulation potential of mefentrifluconazole


Partition coefficient octanol/water

[Log Pow]

3.4 (pH 7)1 EC DAR (EC 2017); Doc ID

2013/1382370

Fish bioconcentration (whole fish)

Rainbow trout, Onchorynchus mykiss

(BCF: 14-day uptake, 7-day

depuration)

385 (BCFKLg)2,3 Appendix J, Table 70; Salinas et

al. (2015c) [EC DAR (EC 2017):

Doc ID 2015/1122811]

1 Mefentrifluconazole is considered to be lipophilic (Log Kow >2)

2 BCFKLg: growth-corrected kinetic bioconcentration factor normalised to 5% lipid content

3 BCFKLg value of 385 should be treated with care (also see additional notes in Table 70)

Degradation and fate of mefentrifluconazole in soil

Information on the degradation and fate of mefentrifluconazole in the soil environment is summarised in

Table 14. Values highlighted in bold are used in the quantitative risk assessment.

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Table 14: Degradation and fate of mefentrifluconazole in soil


Aerobic half-life in soil (laboratory)

Calculated 80th percentile, lab = ≥1000

days1

NA (calculated)

Range: DT50lab (non-normalised) = 201.9

to >1000 days (n = 4)


2014/1275177

DT50lab (non-normalised) = 433.7 days (n

= 1)


2015/1003306

DT50lab (non-normalised) both values

>1000 days (n = 2)


2014/1275178

Anaerobic degradation in soil

(DT50lab) 349, 780 and 899 days


2014/7003496

Aerobic half-life in soil (field)

Calculated 80th percentile, field = 309 days2 NA (calculated)

Range: DisT50field (non-normalised) = 101 to 292 days (n = 6)

Appendix J, Table 64; Jacobson

et al. (2016a) [EC DAR (EC

2017): Doc ID 2015/7006396]

Range: DegT50field (non-normalised) = 185.5 to 846.6 days (n = 6)

Appendix J, Table 65; Schäufele

(2015d) [EC DAR (EC 2017):

Doc ID 2015/1046920] and EC

DAR (EC 2017): Doc ID

2015/1249176

Accumulation behaviour in soil (field)

Accumulation behaviour of BAS 750 F in

soil under field conditions in the United

Kingdom following repeated application

onto winter wheat over several years.

This study is ongoing; no residue data is

presented within the interim report. Only

the study design.


(2015b) [EC DAR (EC 2017):

Doc ID 2015/1076325]

Accumulation behaviour of BAS 750 F in

soil under field conditions in Germany

following repeated application onto winter

barley over several years

This study is ongoing; no residue data is

presented within the interim report. Only

the study design.


(2015c) [EC DAR (EC 2017):

Doc ID 2015/1076326]

Soil photolysis half-life (DT50) 93 days (chlorophenyl-label) and 170

days (triazole-label)

Appendix J, Table 63; Hassink

and Delgado (2014a) [EC DAR

(EC 2017): Doc ID

2014/1181666]

Sorption to soil (Kd)3 Range: 29.75 to 121.5 mL/g

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Lowest value non-sand soil: 30.63 mL/g Appendix J, Table 69; Sacchi

(2016) [EC DAR (EC 2017): Doc

ID 2016/3003661] Sorption to soil (Koc)3

Range: 2511 to 4958 mL/g

Lowest value non-sand soil: 2511 mL/g

Metabolites sorption to soil (Koc)

M750F005 = 7863 mL/g

M750F006 = 4919 mL/g

M750F007 = 3938 mL/g

[Note values are QSAR estimates]


2015/1260816

1 Non-normalised upper 80% lab DT50 of >1000, 543, 201.9, 474.5 (Doc ID 2014/1275177), 433.7 (Doc ID

2015/1003306.), >1000 and >1000 days (Doc ID 2014/1275178)

2 Non-normalised upper 80% field DT50 of 281, 286, 286, 266, 292, 101 (Appendix J, Table 64; Jacobson et al., 2016a),

185.5, 350.6, 267.6, 204.4, 846.6 and 313 days (Appendix J, Table 65; Schäufele, 2015d and Doc ID 2015/1249176)

3 Lowest value non-sandy soil used for risk assessment (Kd/Koc values measured in soils classified as “sand”, “coarse

sand”, “fine sand” or “loamy sand” are excluded as per the GENEECE2 guidance)

General conclusion about environmental fate

Mefentrifluconazole

Degradation and fate in the aquatic environment

Mefentrifluconazole does not meet the criteria to be considered rapidly degradable under the HSNO Act ie

degraded by at least 70% within 28 days, equivalent to a DT50 of 16 days (Doc ID 2014/1239574).

The aerobic mineralisation in surface water study (Doc ID: 2015/1186902) indicates that mefentrifluconazole

degrades extremely slowly in a pure water environment; no significant degradation was observed was

observed for the duration of the study (63 days). Total system DT50 values measured in the aerobic aquatic

metabolism study (water and sediment) were 122 days and 213 days, for the Berghäuser Altrhein system

and Ranschgraben systems, respectively (Doc ID: 2015/1000941). Mefentrifluconazole dissipated rapidly

(maximum DT50 = 1.7 days) from the water phase (likely due to sorption to sediment) and degraded at a

moderate rate in the sediment (maximum DT50 = 396 days).

Rapid photodegradation of mefentrifluconazole was observed in irradiated samples with a DT50 of 2.3 days;

no degradation was observed in the dark control samples (Doc ID 2015/7000233). Hydrolysis was

determined to play no role in the degradation of mefentrifluconazole (Doc ID: 2015/1046919).

Mefentrifluconazole is considered to have a low potential for bioaccumulation with a growth-corrected kinetic

bioconcentration factor (BCFKLG) of 385 (Appendix J, Table 70; Salinas et al., 2015c), which is below the

≥500 L/kg threshold in accordance with the HSNO Act. This value should be treated with care however,

since it was observed in the DAR that if a further concentration had been tested, the BCF value would

potentially increase to 655, which meets the HSNO criteria for the active ingredient to have potential for

bioaccumulation (>500).

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Degradation and fate in the soil environment

In the laboratory, aerobic soil half-lives for mefentrifluconazole range from 202 to >1000 days, with a non-

normalised 80% percentile DT50 of ≥1000 days (Doc IDs 2014/1275177, 2015/1003306 and 2014/1275178).

The exact 80% percentile DT50 could not be determined as some values were indicated as greater than 1000

days. In a field study carried out in the USA, half-lives were shorter and ranged from 101 to 292 days

(Appendix J, Table 64, Jacobson et al., 2016). In a field study performed in Europe DT50 values ranged from

186 to 847 days (Appendix J, Table 65; Schäufele, 2015d, and Doc ID: 2015/1249176). In conclusion

mefentrifluconazole is considered persistent in the soil environment (DT50 > 6 months).

Anaerobically, mefentrifluconazole degrades with half-lives ranging from 349 to 899 days (Doc ID

2014/7003496). Photolysis also plays a role in the degradation of mefentrifluconazole in soil with half-lives of

93 and 170 days measured using a chlorophenyl- and triazole-label, respectively (Appendix J, Table 63;

Hassink and Delgado, 2014a).

Mefentrifluconazole is considered slightly mobile to immobile in soil according to the McCall classification

system (McCall et al. 1981). As such, potential for leaching is considered to be low. This was confirmed in

the field dissipation study by Jacobson et al. (2016, Appendix J Table 64) where there was no significant

movement of mefentrifluconazole residues through the soil profile.

Mefentrifluconazole is considered highly persistent in both the aquatic environment and soil environment

according to Annex D of the HSNO Act (Information requirements and screening criteria), a substance is

considered persistent “if the half-life of the chemical in water is greater than two months, or that its half-life in

soil is greater than six months, or if its half-life in sediment is greater than six months”.

Metabolites

Four major metabolites, defined as per the HSNO Act as metabolites formed in amounts of equal to or more

than 10% of the applied amount of substance and any time-point evaluated during the degradation studies in

the appropriate compartment under consideration (soil or water) were identified.

Three major metabolites were identified in the aqueous photolysis study: M750F005, M750F006 and

M750F007 (Doc ID 2015/7000233). Another major metabolite, M750F001 (1,2,4-triazole) was detected in the

aquatic aerobic metabolism study (Doc ID: 2015/1000941).

It is noted that M750F001 (1,2,4-triazole) has a higher chronic toxicity to earthworms than the parent

mefentrifluconazole (NOEC of 1.0 mg ai/kg vs. 4.0 mg ai/kg). M750F001 (1,2,4-triazole) was only formed at a

maximum of 5.2% in the soil metabolism study and then declined, and therefore does not meet the HSNO

Act threshold of 10% for identifying (and thus consideration of) a major metabolite. As such, M750F001

(1,2,4-triazole) is not considered a major metabolite in soil.

M750F001 1,2,4-triazole will be included in the groundwater risk assessment however, due to its higher

mobility in soil than parent mefentrifluconazole.

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Appendix E: Ecotoxicity

The active ingredient fluxapyroxad contained in Revystar® Fungicide has previously been approved in New


HSR100948) and accordingly will not be reviewed or assessed in the context of this memo.

This section focusses only on the active ingredient mefentrifluconazole, which has not previously been

approved in New Zealand.

Executive summaries and list of endpoints



metabolites were sourced from the mefentrifluconazole DAR unless otherwise stated. Study summaries have

only been included in Appendix J where there are comments in regard to individual studies.

Aquatic toxicity

Table 15 contains the acute and chronic aquatic toxicity test results for the active ingredient

mefentriflucoanzole, and Table 16 contains the acute and chronic aquatic toxicity test results for the major

metabolites of mefentrifluconazole.

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Table 15: Summary of aquatic toxicity data for the active ingredient mefentrifluconazole

Test species Test type and duration Value Reference

Fish Acute

Rainbow trout, Oncorhynchus mykiss 96-hr LC50, flow-through 0.532 mg/L (mean measured) Appendix J, Table 71; Salinas

(2014a) [EC DAR (EC 2017): Doc

ID 2014/1036951]

Zebrafish, Danio rerio 96-hr LC50, flow-through 0.906 mg/L (mean measured) Appendix J, Table 72; Rzodeczko

(2015a) [EC DAR (EC 2017): Doc

ID 2015/1001581]

Sheepshead minnow, Cyprinodon variegates 96-hr LC50, static 0.761 mg/L (mean measured) EC DAR (EC 2017): Doc ID

2014/7002810

Common carp, Cyprinus carpio 96-hr LC50, semi-static 1.126 mg/L (mean measured) EC DAR (EC 2017): Doc ID

2015/1249071

Chronic

Zebrafish, Danio rerio NOEC 36-day, ELS, flow-through 0.027 mg ai/L (mean measured) Appendix J, Table 81; Salinas et al.

(2015a) [EC DAR (EC 2017): Doc

ID 2014/1262160]

NOEC, 140-day full life-cycle,

flow-through

0.022 mg ai/L (mean measured) Appendix J, Table 82; Salinas

(2017a) [Not in DAR. Doc ID

2016/1042889]

Sheepshead minnow, Cyprinodon variegates NOEC 35-day, ELS, flow-through 0.147 mg ai/L (mean measured)1 EC DAR (EC 2017): Doc ID

2015/70000619

Endocrine disruption to fish

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Zebrafish, Danio rerio NOEC 69-day, flow-through ≥0.045 mg ai/L (mean measured) Appendix J, Table 83; Salinas et al.

(2015b) [EC DAR (EC 2017): Doc

ID 2015/1099093]

Invertebrates Acute

Daphnia magna 48-hr EC50 0.944 mg/L (geometric mean

measured)

Appendix J, Table 73; Brzozowska

(2014a) [EC DAR (EC 2017): Doc

ID 2013/1250866]

Americamysis bahia 96-hr EC50, flow-through 1.30 mg/L (mean measured)

Appendix J, Table 74; VanHooser

(2014a) [EC DAR (EC 2017): Doc

ID 2014/7002845]

Eastern oyster, Crassostrea virginica 96-hr EC50, flow-through 0.947 mg ai/L (mean measured) EC DAR (EC 2017): Doc ID

2015/7000021

Chronic

Daphnia magna

NOEC, 21-day, semi-static 0.0091 mg ai/L (time-weighted mean) Appendix J, Table 84; Janson

(2014a) [EC DAR (EC 2017): Doc

ID 2014/1098028]

Mysid shrimp, Americamysis bahia NOEC, 28-day, flow-through 0.0132 mg ai/L (mean measured) EC DAR (EC 2017): Doc ID

2016/7001293

Daphnia pulex

NOEC, 21-day, semi-static 0.0276 mg ai/L (mean measured)2 Appendix J, Table 86; Janson

(2015a) [EC DAR (EC 2017): Doc

ID 2015/1003913]

Daphnia longispina

NOEC, 21-day, semi-static 0.0342 mg ai/L (time-weighted

mean)3

Appendix J, Table 85; Janson

(2015b) [EC DAR (EC 2017): Doc

ID 2015/1003912] and Amendment

Janson (2015c) [EC DAR (EC

2017): Doc ID 2015/1251197]4

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Sediment-dwelling aquatic invertebrates Acute

Chironomus dilutus (spiked sediment) NOEC, 10-day, semi-static 7.08 mg ai/kg dry sediment

(geometric mean measured)

Appendix J, Table 87; Clark

(2015a) [EC DAR (EC 2017): Doc

ID 2015/7000621]

Hyalella azteca (spiked sediment) NOEC, 10-day, semi-static ≥100 mg ai/kg dry sediment (mean

measured)


(2015b) [EC DAR (EC 2017): Doc

ID 2015/7000622]

Leptocheirus plumulosus (spiked sediment) NOEC, 10-day, semi-static >95 mg ai/kg dry sediment (mean

measured)


(2015c) [EC DAR (EC 2017): Doc

ID 2015/7000623]

Chronic

Chironomus riparius (spiked sediment) NOEC, 28-day, semi-static ≥1.158 mg/kg dry sediment (initial

measured)

Appendix J, Table 90; Backfisch

and Weltje (2015a) [EC DAR (EC

2017): Doc ID 2014/1243181]

Algae and aquatic macrophytes

Green alga, Pseudokirchneriella subcapitata 72-hr ErC50, static 1.352 mg/L (geometric mean

measured)

Appendix J, Table 75; Brzozowska

(2014b) [EC DAR (EC 2017): Doc

ID 2013/1250865]

Cyanobacterium, Anabaena flos-aquae 72-hr ErC50, static >3.08 mg/L (geometric mean

measured)5

Appendix J, Table 80; Bergfield

(2015c) [EC DAR (EC 2017): Doc

ID 2015/7000617]

Marine diatom, Skeletonema costatum 72-hr ErC50, static 0.679 mg/L (geometric mean

measured)6


(2015a) [EC DAR (EC 2017): Doc

ID 2015/7000620] and Table 77;

Horn (2016a) [EC DAR (EC 2017):

Doc ID 2016/1292092]

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Freshwater diatom, Navicula pelliculosa 72-hr ErC50, static 1.347 mg/L (geometric mean

measured)7


(2015b) [EC DAR (EC 2017): Doc

ID 2015/7000618] and Table 79;

Horn (2016b) [EC DAR (EC 2017):

Doc ID 2016/1292093]

Duckweed, Lemna gibba 7-day ErC50, static >1.894 mg/L (time-weighted mean)8 EC DAR (EC 2017): Doc ID

2014/1001322

1 Note this endpoint is reported as 0.16 mg/L (nominal) in the BASF list of ecotoxicity endpoints 2 Note this endpoint is reported as 0.0282 mg/L (nominal) in the BASF list of ecotoxicity endpoints 3 Note this endpoint is reported as 0.0338 mg/L (nominal) in the BASF list of ecotoxicity endpoints 4 Amendment (Appendix J, Table 85; Janson, 2015c) only relates to alkalinity and hardness value table where the decimal place was previously in the wrong place 5 Note this endpoint is reported as >3.20 mg/L (initial measured) in the BASF list of ecotoxicity endpoints 6 Note this endpoint is reported as 0.723 mg/L in the BASF list of ecotoxicity endpoints. This value is from the original study (Appendix J, Table 76; Bergfield, 2015a)

rather than the recalculation of endpoints (Appendix J, Table 77; Horn, 2016a) 7 Note this endpoint is reported as 1.57 mg/L in the BASF list of ecotoxicity endpoints, which is the 96-hr value. Typically the 72-hr endpoints are used. 8 Note this endpoint is reported as 2.017 mg/L (initial measured) in the BASF list of ecotoxicity endpoints

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Table 16: Summary of aquatic toxicity data for metabolites of mefentrifluconazole


M750F001 (1,2,4-triazole)

Fish Acute

Rainbow trout, Oncorhynchus mykiss 96-hr LC50 760 mg/L (nominal)1 EC DAR (EC 2017): Doc ID

1983/1000494

Chronic

Rainbow trout, Oncorhynchus mykiss NOEC, 28-days 3.20 mg/L (nominal)1

Appendix J, Table 91; Dorgerloh and

Sommer (2002) [EC DAR (EC 2017):

Doc ID 2002/1007850]

Invertebrates Acute

Daphnia magna 48-hr EC50 >100 mg/L (nominal)1 EC DAR (EC 2017): Doc ID

1995/1001851


Green alga, Pseudokirchneriella subcapitata 72-hr ErC50 >31 mg/L1 (mean measured) EC DAR (EC 2017): Doc ID

2001/1022266

M750F005

Invertebrates Acute

Daphnia magna 48-hr EC50 >8.58 mg/L (geometric mean

measured)


2015/1001490


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Green alga, Pseudokirchneriella subcapitata 72-hr ErC50 >8.572 mg/L (geometric mean

measured)

Appendix J, Table 92; Rzodeczko

(2016b) [EC DAR (EC 2017): Doc ID

2015/1184816]

M750F006

Fish Acute

Rainbow trout, Oncorhynchus mykiss 96-hr LC50 6.20 mg/L (geometric mean

measured)

Appendix J, Table 93, Rzodeczko

(2016c) [EC DAR (EC 2017): Doc ID

2016/1128152]

Invertebrates Acute

Daphnia magna 48-hr EC50 4.42 mg/L (geometric mean

measured)


(2015c) [EC DAR (EC 2017): Doc ID

2015/1001492]


Green alga, Pseudokirchneriella subcapitata 72-hr ErC50 1.424 mg/L (geometric mean

measured)


(2016c) [EC DAR (EC 2017): Doc ID

2015/1184815]

M750F007

Fish Acute

Rainbow trout, Oncorhynchus mykiss 96-hr LC50 >7.20 mg/L (geometric mean

measured)


2015/1001489

Invertebrates Acute

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Daphnia magna 48-hr EC50 >10 mg/L (analytically confirmed

nominal)

Appendix J, Table 96; Backfisch and

Härthe (2015a) [EC DAR (EC 2017):

Doc ID 2015/1003915]


Green alga, Pseudokirchneriella subcapitata 72-hr ErC50 >10 mg/L (nominal) EC DAR (EC 2017): Doc ID

2015/1003914

1 Note that the majority of 1,2,4-triazole studies come from the Epoxiconazole DAR

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Metabolites

Based on the aquatic toxicity endpoints for mefentrifluconazole, as listed in Table 16 above, the parent

mefentrifluconazole is of higher toxicity to aquatic organisms than its major metabolites. As such, metabolites

M750F005, M750F006 and M750F007 have not been considered further in the aquatic risk assessment

since any controls for the parent will be protective of any risks from the metabolites. Metabolites M750F005,

M750F006 and M750F007 all exhibit lower mobility in soil than the parent active ingredient.

Although metabolite M750F001 (1,2,4-triazole) has lower aquatic toxicity than the parent, it will still be

assessed in the groundwater risk assessment due to its higher mobility.

Uncertainties and data gaps

No uncertainties or data gaps were identified in regard to aquatic toxicity of the active ingredient

mefentrifluconazole or its metabolites. It should be noted that no aquatic toxicity data for the formulated

substance Revystar Fungicide were available however. The additive toxicity calculations performed for

Daphnia magna showed that mefentrifluconazole was the driver of toxicity (99% contribution) and therefore,

the risk assessment performed for the active constituent alone can be used to conclude on risk to the end

use product.

General conclusion about aquatic toxicity

The active ingredient mefentrifluconazole triggers a 9.1A HSNO classification (very ecotoxic in the aquatic

environment) based on a 96-hr LC50 for the rainbow trout (Onchorhynchus mykiss) of 0.532 mg/L (Appendix

J, Table 71; Salinas, 2014a), a 48-hr EC50 for Daphnia magna of 0.944 mg/L (Appendix J, Table 73;

Brzozowska, 2014a) and a 96-hr ErC50 for the marine diatom (Skeletonema costatum) of 0.679 mg/L

(Appendix J, Table 76 and Table 77; Bergfield, 2015a and Horn, 2016a).

The formulation Revystar Fungicide triggers a 9.1B HSNO classification (ecotoxic in the aquatic

environment) based on mixture rules.

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Soil toxicity

Table 17 contains the acute and chronic soil toxicity test results for the active ingredient mefentrifluconazole.

Values in bold are those toxicity endpoints used for the risk assessment. Underlined values are those used

to determine the classification.

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Table 17: Summary of soil toxicity data for the active ingredient mefentrifluconazole


Soil organisms

Earthworm, Eisenia fetida Acute, 14-day LC50 (artificial soil, 10% peat) >500 mg ai/kg1

[Uncorrected value >1000 mg ai/kg]

EC DAR (EC 2017): Doc

ID 2015/1003342

NOEC, 56-days, reproduction (artificial soil,

10% peat)

4 mg ai/kg dry soil1

[Uncorrected value = 8 mg ai/kg dry soil]


ID 2013/1235075

Springtail, Folsomia candida NOEC (reproduction and mortality), 28-days

(artificial soil, 5% peat)

≥200 mg ai/kg dry soil1

[Uncorrected value >400 mg ai/kg dry soil]


ID 2013/1235081

Soil mite, Hypoaspis aculeifer NOEC (reproduction and mortality), 14-days

(artificial soil, 5% peat)

≥500 mg ai/kg dry soil1

[Uncorrected value >1000 mg ai/kg dry soil]


ID 2013/1235082

Terrestrial plants

Six dicot and four monocot crop

species

Vegetative vigour, 21 days

Foliar application to seedling plants, 10

species

ER25 >150 g ai/ha2

[derived from an ER25 of >1500 Tl/ha for BAS 750

01 F, containing 100 g/L mefentrifluconazole]

NOER >150 g ai/ha2

[derived from a NOER of >1500 Tl/ha for BAS 750


Appendix J, Table 97;

Marquardt (2015b) [EC


2014/1242738]

Seedling emergence, 21 days

Application to soil surface, 10 species

ER25 >150 g ai/ha2

[derived from an ER25 of >1500 Tl/ha for BAS 750


NOER = 75 g ai/ha2,3


Marquardt (2015a) [EC


2016/7010990]

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[derived from a NOER of >1500 Tl/ha for BAS 750


Soil microbial function

Soil microflora NOEC, nitrogen mineralisation, 28 days 2.53 mg ai/kg dry soil EC DAR (EC 2017): Doc

ID 2015/1108623

NOEC, carbon mineralisation, 28 days 2.53 mg ai/kg dry soil EC DAR (EC 2017): Doc

ID 2016/1042889

1 Original toxicity endpoints from the artificial soil tests have been divided by 2 to account for different soil characteristics and the possibility of reduced bioavailability for

soil organisms of lipophilic substances (Log Pow >2) as per the EFSA Technical Report (EFSA 2015)

2 Note that the test item applied in this study was not Revystar Fungicide but formulation BAS 750 01 F. Whilst this also an emulsifiable concentrate formulation

containing the same concentration of mefentrifluconazole as Revystar Fungicide (100 g/L), formulation BAS 750 01 F does not contain fluxapyroxad however.

3 Note that the NOER value should be treated with caution as the large deviation from the control suggest that the study lacks sensitivity and there is some uncertainty

regarding the NOER value derived.

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No uncertainties or data gaps were identified in regard to soil toxicity for the active ingredient

mefentrifluconazole with the exception of a reliable mefentrifluconazole NOEC value for seedling

emergence as there was some uncertainty regarding the value derived in the study provided

(Marquardt, 2015a).

It should be noted that no soil toxicity data for the formulated substance Revystar Fungicide were

available however. The results of the applicant’s additive toxicity calculations of the end use product

however indicate additive toxicity is not expected due to a lack of toxicity from one or both active

constituents to soil macro-organisms.

General conclusion about soil toxicity

The active ingredient mefentrifluconazole does not trigger the HSNO thresholds for toxicity to the soil

environment based on the data available. The formulation Revystar Fungicide does not trigger a 9.2

HSNO classification based on mixture rules.

Terrestrial vertebrate toxicity

For effects on terrestrial vertebrates other than birds, refer to the mammalian toxicity section.

Table 18 contains the acute and chronic avian toxicity test results for the active ingredient

mefentrifluconazole.

Table 18: Summary of terrestrial vertebrate toxicity data for mefentrifluconazole

Test species Test type and

duration Value Reference

Bobwhite quail,

Colinus virginianus

Acute oral LD50 816 mg ai/kg bw

Appendix J, Table 99; Zok

(2014a) [EC DAR (EC 2017):

Doc ID 2014/1095701]

8-day dietary LC50

[Disregarded study, see

study summary for

comments]


(2014c) [EC DAR (EC 2017):

Doc ID 2014/1127963 plus

amendment; Keller (2015a)

[EC DAR (EC 2017): Doc ID

2015/1223324]

Reproductive 1

generation, 22 weeks

NOEC

285 mg ai/kg diet (25.3 mg

ai/kg bw/day)


Bryden et al. (2014a) [EC


2013/1281276]

Mallard duck, Anas

platyrhynchos Acute oral LD50

3228 mg ai/kg [extrapolated

from >2000 mg/kg bw1]


(2014b) [EC DAR (EC 2017):

Doc ID 2014/1095700]

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8-day dietary LDD50


study summary for

comments]


(2014d) [EC DAR (EC 2017):

Doc ID 2014/1117035]

Reproductive 1

generation, 21 weeks

NOEC

600 mg ai/kg diet (80.5 mg

ai/kg bw/day)


Temple et al. (2015a) [EC


2015/7005819]

Canary, Serinus

canaria Acute oral LD50

3512 mg ai/kg [extrapolated

from >2860 mg ai/kg bw]2

Appendix J, Table 101; Keller

(2015a) [EC DAR (EC 2017):

Doc ID 2015/1085493]

1 Note that according to EFSA (EFSA 2009)in cases where there is no mortality the LD50 can be extrapolated

using a factor of 1.614 (five birds tested at limit dose) by multiplying the limit dose by the extrapolation factor (ie.

2000 x 1.614 = 3228 mg ai/kg). No significant sub-lethal effects were observed.

2 Note that based on the EFSA guidance (EFSA 2009) in cases where there is a single mortality the LD50 can be

extrapolated using a factor of 1.228 (five birds tested at limit dose) by multiplying the limit dose by the

extrapolation factor (ie. 2860 x 1.228 = 3512 mg ai/kg). No significant sub-lethal effects were observed.


No uncertainties or data gaps in regard to ecotoxicity to terrestrial vertebrates has been identified.

The applicant’s additive toxicity calculations show that acute toxicity from the end use product is

expected to be based on mefentrifluconazole.

General conclusion about ecotoxicity to terrestrial vertebrates

Mefentrifluconazole triggers a 9.3C HSNO classification (harmful to terrestrial vertebrates) based on

an LD50 for bobwhite quail (Colinus virginianus) of 816 mg/kg bw (Appendix J, Table 99; Zok, 2014a).

The formulation Revystar Fungicide triggers a 9.3C HSNO classification (harmful to terrestrial

vertebrates) based on mixture rules.

Ecotoxicity to bees and other terrestrial invertebrates

Table 19 contains the toxicity test results for the active ingredient mefentrifluconazole for pollinators.

Table 20 contains the Tier I toxicity test results for the active ingredient mefentrifluconazole for non-

target arthropods.

Table 21 contains the Tier II toxicity test results for the active ingredient mefentrifluconazole for non-

target arthropods.

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Table 19: Pollinators: summary of toxicity data for mefentrifluconazole



Honeybee, Apis

mellifera

LD50 (48-hr), acute

oral

>100 µg ai/bee Appendix J, Table 106;

Franke (2015a); [EC DAR

(EC 2017): Doc ID

2015/1128674] LD50 (48-hr), acute

contact

>100 µg ai/bee

Chronic adult oral

toxicity, 10-days

LD50 (10-day, chronic)

>110.5 µg/bee/day

NOED (10-day, chronic) =

110.5 µg/bee/day


2013/1235086

Honeybee larvae, Apis

mellifera

Bee brood, 96-hr

dietary exposure,

8-day test duration,

larvae

LD50 (96-hrs, acute) = 43.9

µg ai/larva

NOED (96-hrs, acute) = 29.7

µg ai/larva


Kleebaum (2015b) [EC DAR

(EC 2017): Doc ID

2013/1235087]

EC50, ED50, NOEC

and NOED (21

days), repeated

exposure

In vitro


study summary for

comments]


Royer (2015a) [EC DAR (EC

2017): Doc ID 2014/1327676]

Bumble bee, Bombus

terrestris

Acute oral, 96-hr

LD50

>195.4 µg ai/bee1 Appendix J, Table 107;

Amsel (2015a) [EC DAR (EC

2017): Doc ID 2014/1275250] Acute contact, 96-

hr LD50

>200 µg ai/bee1

1 Included as supporting information but not used in risk assessment.

Table 20: Non-target arthropods: summary of toxicity data (Tier I) for mefentrifluconazole



Parasitic wasp,

Aphidius rhopalosiphi

LR50 (48-hrs),

rate-response

0.954 g ai/ha1

[derived from an LR50 95.4

mL/ha for BAS 750 01 F in

200 L water/ha, containing

100 g/L mefentrifluconazole]


2014/1242743

Predatory mite,

Typhlodromus pyri

LR50 (7-days),

glass plate

7.691 g ai/ha1

[derived from an LR50 769.1


200 L water, containing 100

g/L mefentrifluconazole]


2014/1242742

1 Note that the test item applied in this study was not Revystar Fungicide but formulation BAS 750 01 F. Whilst

this also an emulsifiable concentrate formulation containing the same concentration of mefentrifluconazole as

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Revystar Fungicide (100 g/L), formulation BAS 750 01 F does not contain fluxapyroxad and cannot be used as

an indication of mixture toxicity therefore

Table 21: Non-target arthropods: summary of toxicity data (Tier II) for mefentrifluconazole



Parasitic wasp,

Aphidius rhopalosiphi

LR50 (48-hrs),

extended

laboratory study

>300 g ai/ha1

[derived from an LR50 >3000





2015/1020207

Predatory mite,

Typhlodromus pyri

LR50 (48-hrs),

extended

laboratory study

>300 g ai/ha1






2014/1242744

Green lacewing,

Chrysoperla carnea

LR50 (7-days),

extended

laboratory study

(fresh dry

residues)

>300 g ai/ha1






2015/1020206

1 Note that the test item applied in this study was not Revystar Fungicide but formulation BAS 750 01 F. Whilst

this also an emulsifiable concentrate formulation containing the same concentration of mefentrifluconazole as

Revystar Fungicide (100 g/L), formulation BAS 750 01 F does not contain fluxapyroxad and cannot be used as

an indication of mixture toxicity therefore


No uncertainties or data gaps were identified in regard to toxicity to terrestrial invertebrates for the

active ingredient mefentrifluconazole with the exception of chronic toxicity to honey bee larvae since

the study submitted (Appendix J, Table 109; Royer, 2015a) was considered unreliable. It should be

noted that no toxicity to terrestrial invertebrate data for the formulated substance Revystar Fungicide

were available. Additive toxicity for Revystar® Fungicide could not be calculated however due to a

lack of toxicity of the individual active constituents to bees and standard terrestrial invertebrate test

species. The risk of Revystar® Fungicide to these organisms is therefore considered acceptable.

General conclusion about ecotoxicity to bees and terrestrial invertebrate

toxicity

Mefentrifluconazole does not trigger the HSNO thresholds for toxicity to the terrestrial invertebrates

based on the data available. The formulation Revystar Fungicide does not trigger a 9.4 HSNO

classification based on mixture rules.

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Appendix F: Hazard classification of mefentrifluconazole and Revystar® Fungicide

The hazard classifications of mefentrifluconazole and Revystar® Fungicide are listed in Table 22 and

Table 23 respectively.

Table 22: Applicant and Staff classifications of the active ingredient mefentrifluconazole

Hazard Class/Subclass

Active ingredient

classification by:

Method of

classification

Remarks

Ap

plican

t

EP

A S

taff

Test

resu

lts

Read

acro

ss

Class 1 Explosiveness

Applicant did

not self-

classify the

active

Class 2, 3 & 4 Flammability

Class 5 Oxidisers/Organic

Peroxides

Subclass 8.1 Metallic corrosiveness

Subclass 6.1 Acute toxicity (oral) No See Appendix C,

Table 8

Subclass 6.1Acute toxicity (dermal) No See Appendix C,

Table 8

Subclass 6.1 Acute toxicity

(inhalation) No

See Appendix C,

Table 8

Subclass 6.1 Aspiration hazard NA Material is a solid

Subclass 6.3/8.2 Skin

irritancy/corrosion No

See Appendix C,

Table 8

Subclass 6.4/8.3 Eye

irritancy/corrosion No

See Appendix C,

Table 8

Subclass 6.5A Respiratory

sensitisation ND

Subclass 6.5B Contact sensitisation 6.5B See Appendix C,

Table 8

Subclass 6.6 Mutagenicity No See Appendix C,

Table 8

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Subclass 6.7 Carcinogenicity No See Appendix C,

Table 9

Subclass 6.8 Reproductive/

developmental toxicity No

See Appendix C,

Table 9


developmental toxicity (via

lactation)

No See Appendix C,

Table 9

Subclass 6.9 Target organ systemic

toxicity (oral) No

See Appendix C,

Table 9


toxicity (dermal) No

See Appendix C,

Table 9


toxicity (inhalation) ND

See Appendix C,

Table 9

Subclass 9.1 Aquatic ecotoxicity 9.1A

Based on a 96-hour

LC50 of 0.532 mg/L

for the rainbow

trout

Onchorhynchus

mykiss (Salinas,

2014a)

Subclass 9.2 Soil ecotoxicity No See Appendix E,

Table 17

Subclass 9.3 Terrestrial vertebrate

ecotoxicity 9.3C

Based on an LD50

of 816 mg/kg bw for

the bobwhite quail

Colinus virginianus

(Zok, 2014a).

Subclass 9.4 Terrestrial

invertebrate ecotoxicity No

See Appendix E,

Table 18

NA: Not Applicable.

ND: No Data or poor quality data [according to Klimisch criteria (Klimisch, Andreae et al. 1997)]. There is a lack

of data for one or more components.

No: Not classified based on actual relevant data available for the substance. The data are conclusive and

indicate the threshold for classification is not triggered.

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Table 23: Applicant and EPA Staff classifications of Revystar® Fungicide1


Mixture

classification by:

Method of

classification

Remarks

Applicant EPA

Staff

Mix

ture

data

Read

acro

ss

Mix

ture

ru

les

Class 1 Explosiveness No No

Class 2, 3 & 4 Flammability No No

Class 5 Oxidisers/Organic

Peroxides No No

Subclass 8.1 Metallic

corrosiveness No No


(oral) 6.1D 6.1D See Appendix C, Table 7

Subclass 6.1Acute toxicity

(dermal)

Not

triggered No See Appendix C, Table 7


(inhalation) 6.1D 6.1D See Appendix C, Table 7

Subclass 6.1 Aspiration

hazard ND No

See Appendix B, Table 6

(viscosity greater than

the classifiable minimum)

Subclass 6.3/8.2 Skin

irritancy/corrosion 6.3A 6.3A See Appendix C, Table 7

Subclass 6.4/8.3 Eye

irritancy/corrosion 6.4A 6.4A See Appendix C, Table 7

Subclass 6.5A Respiratory

sensitisation ND ND

Subclass 6.5B Contact

sensitisation 6.5B 6.5B See Appendix C, Table 7

Subclass 6.6 Mutagenicity No ND Neither active ingredient

is classified

Subclass 6.7 Carcinogenicity No ND Neither active ingredient

is classified

1 Use of mixture rules may not adequately take into account interactions between different components in some circumstances and must be considered of lower reliability than substance (formulation) data.

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Mixture

classification by:

Method of

classification

Remarks

Applicant EPA

Staff

Mix

ture

data

Read

acro

ss

Mix

ture

ru

les


developmental toxicity No ND

Neither active ingredient

is classified


developmental toxicity (via

lactation)

ND ND Neither active ingredient

is classified

Subclass 6.9 Target organ

systemic toxicity (oral) No 6.9B

Fluxapyroxad triggers

classification


systemic toxicity (dermal) No ND

Fluxapyroxad and

mefentrifluconazole are

ND


systemic toxicity (inhalation) No ND

Fluxapyroxad and

mefentrifluconazole are

ND

Subclass 9.1 Aquatic

ecotoxicity 9.1B 9.1B

Subclass 9.2 Soil ecotoxicity No ND


vertebrate ecotoxicity No 9.3C


invertebrate ecotoxicity No ND

NA: Not Applicable. For instance testing for a specific endpoint may be omitted if it is technically not possible to

conduct the study as a consequence of the properties of the substance: eg very volatile, highly reactive or

unstable substances cannot be used, mixing of the substance with water may cause danger of fire or explosion

or the radio-labelling of the substance required in certain studies may not be possible.

ND: No Data or poor quality data [according to Klimisch criteria (Klimisch, Andreae et al. 1997)]. There is a lack

of data for one or more components.

No: Not classified based on actual relevant data available for the substance or all of its components. The data

are conclusive and indicate the threshold for classification is not triggered.

The proposed toxicity classification of Revystar® Fungicide is: 6.1D acute toxicity (oral and

inhalation), 6.3A, 6.4B, and 6.5B for skin and eye irritation, and contact sensitisation, respectively. It is

classified 6.9B specific organ toxicity due to fluxapyroxad.

The proposed ecotoxicity hazard classification of Revystar® Fungicide is: 9.1B (ecotoxic in the

aquatic environment) and 9.3C (harmful to terrestrial vertebrates). The EPA staff classification of

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Revystar® Fungicide differed from that of the applicant in that they did not classify it for toxicity to

terrestrial vertebrates.

The EPA staff classification of Revystar® Fungicide differed from that of the applicant in that the

applicant classified it as “No” for several endpoints, whereas, the EPA classified it as ND as the EPA

took into account the ND classification for sub-components.

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Appendix G: Human health risk assessment

Quantitative risk assessment

The operator exposure assessment is based on a modification of the approach used by European

regulators, taking into account New Zealand specific factors. The model is based on the results of

actual measurements carried out in the field and has an established history of providing reliable and

reproducible results.

The re-entry worker exposure assessment is based on a modification of the approach used by

European regulators and the US-EPA. The parameters for the modelling are based on empirical data

relating to measurements of dermal exposure of workers from contact with residues on foliage for

various activities and the amount of foliar residues that are dislodgeable.

The bystander exposure assessment is based on a modification of the approaches used by European

regulators and the US-EPA. Spray drift deposition from ground based application is estimated using

the AgDrift model using the curves produced by the Australian Pesticides and Veterinary Medicines

Authority [APVMA, (APVMA 2010)]. The parameters are based on empirical data. Spray drift

deposition from aerial application is estimated using the AGDISP model along with appropriate New

Zealand input parameters.

Full details of the methodology can be found in the EPA risk assessment methodology document

(EPA 2018).

To assess risks the predicted systemic exposures to the active ingredient(s) are compared with an

acceptable operator exposure limit (AOEL) for the active ingredient and a risk quotient (RQ) is

calculated. RQ values greater than one indicate that predicted exposures are greater than the AOEL

and potentially of concern. RQ values below one indicate that predicted exposures are less than the

AOEL and are not expected to result in adverse effects.

Input values for the human health risk assessment

Reference doses for mefentrifluconazole established by internationally reputable regulatory

authorities are summarised in Table 24.

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Table 24: AOEL reference dose for mefentrifluconazole established by the EPA

Active

Ingredient

Key systemic

effect

NOAEL

mg/kg

bw/day

Uncerta

inty

factors

Reference

value

(AOEL)

mg/kg

bw/day

Staff’s

modifications Remarks

mefentrifluco

nazole

increase in blood

parameters,

increase liver wt

and altered liver

cell morphology

11 100 0.11 None

90-day

study in

mice

The reference value for mefentrifluconazole was derived from the NOAEL observed in the 90 day

study in mice summarized in the European Commission Draft Assessment Report (EC 2017) Volume

3 – B.6 (AS).

Other input values for the exposure assessment are summarised in Table 25.

Dermal absorption data were provided for Revystar® Fungicide so default values were not utilised.

The results of this study indicate mefentrifluconazole in Revystar® is poorly absorbed (0.36 ± 0.26%)

through the skin as a concentrate (100 mg/mL) and when diluted 1:200 with water (0.5 mg/ml) into an

in-use spray dilution (2.82 ± 0.98%). Due to variation in the data the values used in the risk

assessment were the average plus one SD and rounded up to 1% for the concentrate and 4% for the

dilution. These were the same values the applicant utilised in their risk assessment.

Table 25: Input values for human exposure modelling

Operator exposure assessment

The results of the operator exposure assessment are shown in Table 26.

Active ingredient Physical

form

Concentration

of each active

(%)

Maximum

application rate

(for each

active, for each

method of

application)

g ai/ha

Dermal absorption (%) AOEL

mg/kg

bw/day

Concentrate Spray

mefentrifluconazole liquid 100 150 1 4 0.11

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Table 26: Output of operator mixing, loading and application exposure assessment for

mefentrifluconazole

Exposure Scenario - cereals

Estimated operator

exposure (mg/kg

bw/day)

Risk

Quotient

Boom

No personal protective equipment (PPE)2 during mixing, loading and

application

0.0115 0.10

Gloves only during mixing and loading 0.0092 0.08

Gloves only during application 0.0100 0.09

Full PPE during mixing, loading and application (excluding respirator) 0.0009 0.01

Full PPE during mixing, loading and application (including FP1, P1 and

similar respirator achieving 75 % inhalation exposure reduction)

0.0008 0.01

Full PPE during mixing, loading and application (including FP2, P2 and

similar respirator achieving 90 % inhalation exposure reduction)

0.0008 0.01

Predicted operator exposures to mefentrifluconazole are below the Acceptable Operator Exposure

Level (AOEL) for each use pattern, even without the use of personal protective equipment (PPE).

Therefore operator exposures are not expected to result in adverse health effects

Although the quantitative risk assessment indicates that PPE is not required to ensure that exposures

are below the AOEL, the requirements under HSW (HS), and in particular Regulations 13.7 and 13.8,

state that personal protective equipment is to be used to minimise risks to the health and safety of

workers.

2 ‘Full PPE’ includes: gloves, hood/visor, coveralls, and heavy boots during application and gloves during mixing and loading.

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Re-entry worker exposure assessment

The results of the re-entry worker exposure assessment are summarised in Table 27.

Table 27: Output of the re-entry worker exposure assessment for mefentrifluconazole

Active

ingredient Crop/activity

Internal

(absorbed)

dose available

for systemic

distribution

(mg/kg bw/8

hours)

AOEL

(mg/kg

bw/day)

Risk

Quotient

immediately

after

application

Re-

entry

interval

without

gloves

Re-

entry

interval

with

gloves

mefentrifluconazole

Cereals (scouting, irrigation, weeding mature/full foliage plants)

0.00 0.11 0.02 0.0 0.0

Predicted exposures to mefentrifluconazole for workers re-entering and working in areas where

Revystar® Fungicide has been applied are below the AOEL. No re-entry intervals are necessary.

Quantitative bystander risk assessment

It is considered that the main potential source of exposure to the general public for substances of this

type (other than via food residues which will be considered as part of the registration of this substance

under the Agricultural Compounds and Veterinary Medicines (ACVM) Act 1997 is via spray drift. In

terms of bystander exposure, toddlers are regarded as the most sensitive sub-population and are

regarded as having the greatest exposures. For these reasons, the risk of bystander exposure is

assessed in this sub-population. The AOEL calculated for the operator and re-entry worker exposure

assessments has been used for the bystander assessment, as the use of an oral chronic reference

dose (CRfD) is usually likely to be over precautionary.

The results of the bystander exposure assessment are summarised in Table 28.

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Table 28: Output of the bystander exposure assessment for mefentrifluconazole

Exposure Scenario – cereal

Estimated exposure of

15 kg toddler exposed

through contact to

surfaces 8 m from an

application area

(µg/kg bw/day)

Risk Quotient

Buffer zone needed

to reduce toddler

exposure to the

AOEL

Boom

High boom, fine droplets 0.30 0.0027 0

High boom, coarse droplets 0.05 0.0004 0

Low boom, fine droplets 0.10 0.0009 0

Low boom, coarse droplets 0.02 0.0002 0

Aerial - agriculture

Swath width 20 m, Med-coarse

droplet size

0.41 0.0038 0

Swath width 20 m, coarse- v.

coarse droplets

0.31 0.0028 0

Swath width 20 m, extremely

coarse droplets

0.21 0.0019 0

Swath width 24 m, v. fine-fine

droplets

1.24 0.0112 0

Swath width 24 m, fine-med.

droplets

0.61 0.0056 0

Swath width 24 m, med.-coarse

droplets

0.41 0.0037 0

Estimated bystander exposure from spray drift after application of Revystar® Fungicide to cereals is

below the AOEL. No buffer zone is required to protect bystanders.

Conclusions of the human health risk assessment

It is considered that the risks to human health from the proposed use of Revystar® Fungicide are

acceptable without the use of Personal Protective Equipment (PPE), application of re-entry intervals,

or enforcement of no-spray buffer zones to protect bystanders.

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Appendix H: Environmental risk assessment

Mixture toxicity

No product-specific ecotoxicity data is available for the formulated substance Revystar® Fungicide

(BAS 752 00 F).

The applicant has performed a mixture toxicity assessment, which establishes which active ingredient

mostly contributes to the toxicity for each area of the risk assessment, assuming additivity, following

EFSA Guidance (EFSA 2013). This is based on the individual toxicity endpoints for each of the active

ingredients fluxapyroxad and mefentrifluconazole, and their relative contribution to the formulation.

This approach does not establish whether toxicity of the mixture as a whole is additive or non-additive

however. As such, whether the formulated product Revystar® Fungicide (BAS 752 00 F) is found to

behave in a more than additive manner (eg synergism) remains an uncertainty and it’s possible that

the conclusions of the risk assessment may underestimate the risks.

Following publication of the US EPA’s Environmental Fate and Ecological Risk Assessment for

mefentrifluconazole (US EPA 2019) and the Canadian Pest Management Regulatory Agency’s

(PMRA) Proposed Registration Decision for mefentrifluconazole and related use end products (PMRA

2019), it is apparent that ecotoxicity formulation data are available for other mefentrifluconazole-

containing formulations. The EPA has therefore performed a mixture toxicity assessment, also

following the EFSA guidance (EFSA 2013) based on this information, and the results are outlined

under the headings below.

Aquatic environment

There are no product-specific aquatic ecotoxicity data available for the formulated substance

Revystar® Fungicide (BAS 752 00 F).

The acute aquatic toxicity (assuming additivity) of the solo mefentrifluconazole formulation (BAS 750

01 F) has been predicted for fish and Daphnia using the toxicity of the pure mefentrifluconazole active

ingredient and the blank formulation (BAS 750 BS F), which contains the same co-formulants as

Revystar® Fungicide (BAS 752 00 F) with the exception of the active ingredients. This prediction was

compared with the actual acute toxicity of the solo mefentrifluconazole formulation (BAS 750 01 F).

For both fish and Daphnia, it was determined that the interactions between the pure technical grade

active ingredient mefentrifluconazole and the other formulation components do not deviate from

additivity (Model Deviation Ratios (MDRs) of 3 and 2, respectively); in other words this is “in

agreement” and is what would be expected based on the sum of the effects of chemicals involved in

the reaction).

It should be noted however that BAS 750 01 F is only a solo (mefentrifluconazole) formulation and

does not contain the active ingredient fluxapyroxad. The effect on the interaction of the components

by adding the second active ingredient fluxapyroxad is unknown. This is an uncertainty as it is not

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possible to predict what the interactions between the components in the mixture with both active

ingredients would be. It is therefore also not possible to conclude that mefentrifluconazole alone is

driving the toxicity as it cannot be determined if the components in the formulation still interact in an

additive manner when fluxapyroxad is added.

In conclusion there is the potential for the actual formulation to deviate from additivity due to the

inclusion of the second active ingredient fluxapyroxad, and the proposed controls may not be

conservative enough therefore (in case of a more than additive interaction).

It is important to note here however that the endpoint selected for use in the refined aquatic risk

assessment is a chronic NOEC of 0.0091 mg/L (21-day) for Daphnia magna obtained for the pure

active ingredient mefentrifluconazole (see the aquatic risk assessment below). This value is between

58 to 104 times lower than the most sensitive mefentrifluconazole acute toxicity endpoints for fish,

aquatic invertebrates and algae, and is considered a worst-case scenario. Although there is the

potential that a synergistic effect may occur on a chronic basis as a result of the addition of

fluxapyroxad, this would not affect the aquatic risk assessment, and would not change the buffer zone

calculation.

Soil environment

EPA conclusion

There is no product-specific soil toxicity data are available for the formulated substance Revystar®

Fungicide (BAS 752 00 F). No toxicity to earthworms has been demonstrated in the two-way mixture

formulation BAS 752 01 F (containing the active ingredients mefentrifluconazole and fluxapyroxad but

this is not Revystar) however, and as such interactions between these two active ingredients are

considered unlikely. There is a very low concern therefore that the toxicity will deviate from additivity

as interactions being very strongly more than additive (eg synergism) would likely have been seen in

toxicity of the mixture.

It should be noted that BAS 752 01 F is not the actual formulation undergoing assessment however,

and different co-formulants can impact overall toxicity and interactions. It is considered likely that the

formulated product Revystar® Fungicide (BAS 752 00 F) behaves in a similar manner to BAS 752 01

F, and therefore the current soil risk assessment is considered acceptable.

Terrestrial vertebrates

EPA conclusion

No product-specific terrestrial vertebrate toxicity data are available for the formulated substance

Revystar® Fungicide (BAS 752 00 F). No toxicity to birds has been demonstrated in the two-way

mixture formulation BAS 752 01 F (containing the active ingredients mefentrifluconazole and

fluxapyroxad but different co-formulants to Revystar® Fungicide (BAS 752 00 F)) however. As such,

more than additive interactions between these two active ingredients are considered unlikely. There is

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a very low concern that the toxicity will deviate from additivity therefore, as interactions being very

strongly more than additive (eg synergism) would likely have been seen in toxicity of the mixture.




F however, and as such the current terrestrial vertebrate risk assessment is considered acceptable.

Terrestrial invertebrates

EPA conclusion

No product-specific terrestrial invertebrate toxicity data are available for the formulated substance

Revystar® Fungicide (BAS 752 00 F), no toxicity to honey bees has been demonstrated in the two-

way mixture formulation BAS 752 01 F (containing the active ingredients mefentrifluconazole and

fluxapyroxad but different co-formulants to Revystar® Fungicide (BAS 752 00 F)) however, and as

such interactions between these two active ingredients are considered unlikely. There is therefore a

very low concern that the toxicity will deviate from additivity as interactions being very strongly more

than additive (eg synergism) would likely have been seen in toxicity of the mixture.




F, and therefore the current terrestrial invertebrate risk assessment is considered acceptable.

EPA’s final conclusion

For the aquatic environment, based on the available information it is it is not possible to predict what

the interactions between the components in the mixture with both active ingredients would be. It is not

possible to conclude that mefentrifluconazole alone is driving the toxicity as there might be

interactions between the components impacting the overall toxicity. There is still the potential for the

components of the actual formulation to interact in a manner that deviates from additivity, therefore

the proposed controls may not be conservative enough to account for this uncertainty.

It is important to note here however that the endpoint selected for use in the refined aquatic risk

assessment is a chronic NOEC of 0.0091 mg/L (21-day) for Daphnia magna obtained for the pure

active ingredient mefentrifluconazole (see the aquatic risk assessment below). This value is between

58 to 104 times lower than the most sensitive mefentrifluconazole acute toxicity endpoints for fish,

aquatic invertebrates and algae, and is considered a worst-case scenario. Although there is the

potential that a synergistic effect may occur on a chronic basis as a result of the addition of

fluxapyroxad, this would not affect the aquatic risk assessment, and would not change the buffer zone

calculation.

For the terrestrial environment, although there is still uncertainty in regard to mixture toxicity of

Revystar Fungicide, no strong synergistic reactions between active ingredients are expected for soil,

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bees, non-target arthropods and birds as another two-way mixture formulation containing the same

active ingredients is not toxic to any of these terrestrial organisms. It should be noted that this is not

the actual formulation. This uncertainty is considered acceptable because the formulated product

Revystar Fungicide is likely not toxic, assuming other formulation components are not highly toxic.

The current risk assessment for the terrestrial environment is considered acceptable.

Quantitative environmental risk assessment

The active ingredient fluxapyroxad contained in Revystar® Fungicide, approved in New Zealand in

other formulations for use on cereal grains at a similar application rate (Adexar, application

APP201884, approval HSR100948), has not been reviewed or assessed in the context of this memo.

This environmental risk assessment focusses only on the active ingredient mefentrifluconazole, which

has not previously been approved in New Zealand.

Aquatic risk assessment

The basis for the aquatic risk assessment is a comparison of the Expected Environmental

Concentrations (EEC) with toxicity endpoints to which safety factors have been applied. The EEC is

divided by the toxicity endpoint to calculate a risk quotient (RQ) value. The methodology for the aquatic

risk assessment, including the level of concern (LOC) ascribed to specific RQ values, is described in

detail in the EPA standard risk assessment methodology (EPA 2018).

Calculation of expected environmental concentrations

The parameters used in GENEEC2 modelling are listed in Table 29. As an initial worst-case scenario

the aerobic soil DT50 from the laboratory studies was used as an initial conservative evaluation. It was

noted by the staff that the field DT50 values were lower which could potentially be used to refine the

risk assessment.

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Table 29: Input parameters for GENEEC2 analysis for mefentrifluconazole

Parameters Application method Revystar® Fungicide

Crop(s) Cereals

Application rate (g/ha) 150 g ai/ha

Application rate (lbs/acre) 0.1338

Application frequency 2 (maximum)

Application interval (days) 21

Kd (mL/g) 30.63 (lowest value non-sand soil)

Aerobic soil DT50 (days) 1000 (80th percentile, lab)1

Pesticide wetted in? No

Methods of application Ground spray, high-boom Aerial spray

Droplet size Medium to coarse2 Coarse to very coarse2

‘No spray’ zone 0

Depth of incorporation (in) 0 (ground-spray application), not applicable for aerial application

Water solubility (ppm) 0.81

Aerobic aquatic DT50 whole

system (days) 213 (worst-case)

Aqueous photolysis DT50

(days) 2.3

1 Note that if the 80th percentile field value of 309 days is entered as the DT50 value instead of the laboratory DT50

value (1000 days), this makes no difference to the EEC values

2 Droplet sizes specified and confirmed by the applicant

Output from the GENEEC2 model

Ground-based application

RUN No. 1 FOR mefentrifluconaz ON cereals * INPUT VALUES *

--------------------------------------------------------------------

RATE (#/AC) No.APPS & SOIL SOLUBIL APPL TYPE NO-SPRAY INCORP

ONE(MULT) INTERVAL Kd (PPB ) (%DRIFT) ZONE(FT) (IN)

--------------------------------------------------------------------

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0.134( 0.266) 2 21 30.6 810.0 GRHIME( 1.2) 0.0 0.0

FIELD AND STANDARD POND HALFLIFE VALUES (DAYS)

--------------------------------------------------------------------

METABOLIC DAYS UNTIL HYDROLYSIS PHOTOLYSIS METABOLIC COMBINED

(FIELD) RAIN/RUNOFF (POND) (POND-EFF) (POND) (POND)

--------------------------------------------------------------------

1000.00 2 0.00 2.30- 285.20 213.00 121.93

GENERIC EECs (IN MICROGRAMS/LITER (PPB)) Version 2.0 Aug 1, 2001

--------------------------------------------------------------------

PEAK MAX 4 DAY MAX 21 DAY MAX 60 DAY MAX 90 DAY

GEEC AVG GEEC AVG GEEC AVG GEEC AVG GEEC

--------------------------------------------------------------------

2.73 2.69 2.48 2.08 1.84

Aerial application

RUN No. 1 FOR mefentriflucaonz ON cereals * INPUT VALUES *

--------------------------------------------------------------------

RATE (#/AC) No.APPS & SOIL SOLUBIL APPL TYPE NO-SPRAY INCORP

ONE(MULT) INTERVAL Kd (PPB ) (%DRIFT) ZONE(FT) (IN)

--------------------------------------------------------------------

0.134( 0.266) 2 21 30.6 810.0 AERL_D( 7.1) 0.0 0.0

FIELD AND STANDARD POND HALFLIFE VALUES (DAYS)

--------------------------------------------------------------------

METABOLIC DAYS UNTIL HYDROLYSIS PHOTOLYSIS METABOLIC COMBINED

(FIELD) RAIN/RUNOFF (POND) (POND-EFF) (POND) (POND)

--------------------------------------------------------------------

1000.00 2 0.00 2.30- 285.20 213.00 121.93

GENERIC EECs (IN MICROGRAMS/LITER (PPB)) Version 2.0 Aug 1, 2001

--------------------------------------------------------------------

PEAK MAX 4 DAY MAX 21 DAY MAX 60 DAY MAX 90 DAY

GEEC AVG GEEC AVG GEEC AVG GEEC AVG GEEC

--------------------------------------------------------------------

3.18 3.14 2.90 2.45 2.16

The maximum Estimated Environmental Concentrations (EEC) for mefentrifluconazole when applied

as the formulated substance Revystar® Fungicide as estimated by GENEEC2 are 2.73 μg/L and 3.18

µg/L for ground-spray and aerial applications, respectively.

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Calculated risk quotients

The calculated acute risk quotients for each trophic level considering the above EEC and lowest

relevant toxicity figures are presented in Table 30. The calculated chronic risk quotients are presented

in Table 31.

Table 30: Acute risk quotients derived from the GENEEC2 model and toxicity data

Species

Peak EEC

from

GENEEC2

(mg/L)

LC50 or

EC50

(mg/L)

Acute

RQ Conclusion


Fish, Oncorhynchus

mykiss

0.00273 0.532 0.0051 Below LOC for non-threatened

and threatened species

Crustacea, Daphnia

magna



Marine diatom,

Skeletonema costatum1



Aquatic plants, Lemna

gibba

0.00273 >1.894 <0.0014 Below LOC for non-threatened


Aerial application

Fish, Oncorhynchus

mykiss



Crustacea, Daphnia

magna



Marine diatom,

Skeletonema costatum



Aquatic plants, Lemna

gibba

0.00318 >1.894 <0.0017 Below LOC for non-threatened


1 Note that the most sensitive algae toxicity endpoint was determined from a marine species Skeletonema

costatum. The environmental risk assessment is typically based on freshwater species. Since no risks are

identified however, this has been left as is for conservatism

Table 31: Chronic risk quotients derived from the GENEEC2 model and toxicity data

Species

Relevant

EEC from

GENEEC2

(mg/L)

NOEC

(mg/L)

Chronic

RQ Conclusion


Fish, Danio rerio 0.00184

(90-day)1

0.022

(140-day) 0.084

Below LOC for non-threatened and

threatened species

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Species

Relevant

EEC from

GENEEC2

(mg/L)

NOEC

(mg/L)

Chronic

RQ Conclusion

Crustacea, Daphnia

magna

0.00248

(21-day)1

0.0091

(21-day) 0.27

Below LOC for non-threatened

species

Above LOC for threatened

species

Aerial application

Fish, Danio rerio 0.00216

(90-day)1

0.022

(140-day) 0.098

Below LOC for non-threatened and

threatened species

Crustacea, Daphnia

magna

0.00290

(21-day)1

0.0091

(21-day) 0.32


species


species

1 Relevant Expected Environmental Concentrations from GENEEC2 were selected to be as close as possible to

the chronic toxicity endpoints.

It should be noted that the chronic risk to threatened fish species from aerial application is just below

the trigger level of 0.1. Since the refinement will be based on the most sensitive endpoint however

(chronic toxicity to Daphnia), this is considered to be protective of chronic risks to threatened fish

species.

As a refinement for the risks to threatened species of crustaceans the non-normalised soil DT50 from

the field studies was used (309 days). The expected environmental concentration (EEC) at 21 days

after application was 2.43 µg/L and 2.86 µg/L for ground based and aerial applications, respectively.

This refinement still results in an RQ above the level of concern for threatened crustaceans however.

Refinement of the aquatic risk assessment

Predicted exposures are above the level of concern for chronic risks to threatened species of aquatic

invertebrates (Daphnia magna) for mefentrifluconazole following application of Revystar Fungicide to

cereals by both ground-based and aerial application. The scenario modelled is a worst-case, using

the maximum application rate at the shortest interval and maximum frequency of application. Since

risks were identified further modelling was performed to consider whether buffer zones may be able to

mitigate risks from spray drift and runoff.

Spray drift

The Agdrift model was used to calculate the required downwind buffer zone to protect the aquatic

environment from adverse effects of the substance due to spray drift using application from a high

boom [see Table 32 and relevant spray drift scenarios (APVMA 2010)].

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For aerial application, the AGDisp® model was used to calculate the deposition curves. This used the

EPA’s standard assumptions regarding aerial application of fungicides to agricultural land [see EPA

risk assessment methodology (EPA 2018)] with the following exceptions.

Droplet size: ASABE Coarse droplets

Water volume: 60 L/ha

Active fraction: 0.0025

Non-volatile fraction: 0.00375

Exact buffer zones are impractical and too precise to be applied in the real world. Therefore, the

buffer zone distance is rounded so it can be visualized and remembered by end-users.

Table 32: Input parameters and calculation of spray drift buffer zone for the refined risk

assessment of mefentrifluconazole

Input parameters Ground-based Aerial

Application rate (kg ai/ha) 0.150 0.150

Number of applications 2 2

Application interval 21 days 21 days

Application method High boom, medium droplets ASABE coarse droplets

Koc (mL/g) 2511 2511

DT50 (soil) 1000 days 1000 days

DT50 (whole system) 213 days 213 days

Toxicity endpoint 0.0091 mg/L (NOEC, 21-day,

Daphnia magna)

0.0091 mg/L (NOEC, 21-day,

Daphnia magna)

Assessment factor 10 10

Buffer zone (m) – model 0 m 0 m

Buffer zone (m) – control 0 m 0 m

Runoff

The REXTOX model was used to calculate the required buffer zone to protect the aquatic

environment from adverse effect s of the substance due to runoff (see Table 33).

Table 33: Input parameters and calculation of runoff buffer zone for the refined risk

assessment

Input parameters Mefentrifluconazole

Application rate (kg ai/ha) 0.150

Koc 2511 mL/g

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DT50 soil 1000 days

Toxicity endpoint 0.0091 mg/L (NOEC, 21-day, Daphnia magna)

Assessment factor 10

Buffer zone (m) – model 0

Buffer zone (m) – control 0

No runoff buffer zone is necessary following application of the active ingredient mefentrifluconazole,

following application of the formulated substance Revystar Fungicide.


No uncertainties or data gaps have been identified.

Conclusions of the aquatic risk assessment

Predicted exposures concentrations of mefentrifluconazole, applied as the formulated product

Revystar® Fungicide resulted in calculated RQs above the LOC for the aquatic environment. Chronic

risks to threatened species of aquatic invertebrates were identified for both ground-based (RQ = 0.27,

LOC = 0.1) and aerial applications (RQ = 0.32, LOC = 0.1). A refinement of the soil DT50 did not result

in risk below the level of concern in the screening step. The following controls are proposed to reduce

exposures below the level of concern:

Use restrictions

The maximum application rate is 150 g mefentrifluconazole/ha, maximum two

applications/year, and a minimum interval between applications of 21 days

Apply with ground-based equipment and minimum medium droplets, as defined by the

American Society of Agricultural and Biological Engineers ASABE Standard (S572) or the

British Crop Production Council guideline. This information should be required on the

label so that users are aware of this control.

For aerial application, use minimum coarse droplets, as defined by the American Society

of Agricultural and Biological Engineers ASABE Standard (S572) or the British Crop

Production Council guideline. This information should be required on the label so that

users are aware of this control.

A label statement indicating: “DO NOT apply when wind speeds are less than 3 km/hr or

more than 20 km/hr as measured at the application site”.

Groundwater risk assessment

The predicted concentration of the active ingredient mefentrifluconazole and its relevant metabolite

1,2,4-triazole in groundwater, calculated using the Sci-Grow model, is shown in Table 34. The

concentration is initially compared to the EU limit for the maximum permissible concentration of

pesticide active ingredients and their relevant metabolites of 0.1 µg/L.

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Table 34: Input parameters for Sci-Grow analysis and resulting PEC values

Input parameters Mefentrifluconazole Metabolite M750F001

(1,2,4-triazole)

Application rate (kg ai/ha) 0.150 0.0013551

Application rate (lb ai/acre)2 0.1338 0.001209

Number of applications 2 2

Koc3 2511 mL/g (lowest value

non-sand soil)

43 mL/g (lowest value non-

sand soil, n = 5)4

Aerobic soil DT50 (days) 1000 (80th percentile lab

DT50, n = 7)

92.8

PECgw (µg/L) 0.0192 0.00779

1 Formula to calculate equivalent metabolite application rate: (metabolite molecular weight / parent molecular

weight) * (metabolite maximum percent formed /100) * parent application rate (kg ai/ha) ie.

(69.1/397.8)*(5.2/100)*0.15 = 0.001329 kg ai/ha

2 The application rate is conversion from kg ai/ha to lb/acre (the units required to be entered into the model) by

multiplying it by 0.892

3 Lowest Koc from a non-sandy soil (normalised values for the OC, temp and pH)

4 The Koc and aerobic soil DT50 values for metabolite 1,2,4-triazole were taken from APP203363

For mefentrifluconazole and its metabolite 1,2,4-triazole, the concentration is below the 0.1 µg/L

trigger level set by the European regulators. Therefore, risks to groundwater are considered below the

level of concern.

Conclusions of the groundwater risk assessment



groundwater are considered below the level of concern.

Sediment risk assessment

The sediment risk assessment for the active ingredient mefentrifluconazole was performed following

the method outlined in the EPA standard risk assessment methodology (EPA 2018).

The input parameters used in the risk assessment are summarised in Table 35.

Table 35: Mefentrifluconazole input values and calculations for sediment risk assessment

Input parameters Ground-based application Aerial application

Predicted Environmental

Concentration (PEC) local water1

0.00273 mg/L 0.00318 mg/L

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Toxicity value

≥1.158 mg ai/kg dry sediment

(worst-case NOEC, 28-days,

Chironomus riparius)

≥1.158 mg ai/kg dry sediment

(worst-case NOEC, 28-days,

Chironomus riparius)

Assessment factor2 10 10

Koc 2511 mL/g (lowest value non-sand

soil)

2511 mL/g (lowest value non-sand

soil)

PEC local sediment 0.1512 mg/kg 0.1512 mg/kg

RQ ≤1.31 ≤1.52

1 Peak EEC values from GENEEC2

2 Four sediment toxicity tests are available for four different sediment-dwelling organisms. Although three of these

studies are described as “acute” and only one as “chronic” (long-term), sub-lethal endpoints were derived for two

out of three of the acute studies. As such, an assessment factor of 10 was applied as three tests (one long-term

test plus two acute tests with sub-lethal endpoints derived) were available with species representing different

living and feeding conditions.

Conclusions of the sediment risk assessment





for Chironomus riparius). The No Observed Effect Concentration (NOEC) determined in this case was

the highest concentration tested, and no significant effects were observed at this concentration. If a

higher concentration had been tested, the NOEC could potentially be higher, thus resulting in a lower

risk.



or non-target arthropods), and other regulators (EFSA 2018) concluded that risks to sediment-

dwelling organisms were low, risks to sediment-dwelling organisms are considered to be low.

Terrestrial risk assessment

The terrestrial risk assessment considers the risks to soil organisms, terrestrial plants, birds, bees and

non-target arthropods.

The methodology for the terrestrial risk assessment is described in the EPA standard risk assessment

methodology (EPA 2018)

Soil macro-organisms

The soil organism risk assessment is based on a comparison of the Predicted Environmental

Concentrations (PECs) with toxicity values for the substance. The toxicity value is divided by the PEC

to give a Toxicity Exposure Ratio (TER). The different levels of concern assigned to TER values are

listed in the EPA standard risk assessment methodology (EPA 2018).

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The results of the acute risk assessment for soil organisms are summarised in Table 36.

Table 36: Acute TER values for soil organisms

Species

LC50

(mg/kg

soil)

Drift (%)

PEC

(mg/kg

soil)

TER

acute Conclusion

Scenario – mefentrifluconazole, two applications to cereals at 150 g ai/ha – “in-field”

Earthworm,

Eisenia fetida >500 NA 0.40 >1259

Below LOC for threatened/non-

threatened species

Scenario – mefentrifluconazole, two applications to cereals at 150 g ai/ha – “off-field”

Earthworm,

Eisenia fetida >500 2.38 0.009 >52903


threatened species

Acute toxicity exposure ratios (TERs) for soil organisms for the active ingredient mefentrifluconazole

following application of Revystar® Fungicide are below the level of concern (LOC) for non-threatened

and threatened species.

Table 37: Chronic TER values for soil organisms (Tier I1)

Species

NOEC

(mg/kg

soil)

Drift (%)

PEC

(mg/kg

soil)

TER

chronic Conclusion

Scenario – mefentrifluconazole, two applications to cereals at 150 g ai/ha – “in-field”

Earthworm,

Eisenia fetida 4.0 NA 0.40 10.1


species


species

Scenario – mefentrifluconazole, two applications to cereals at 150 g ai/ha – “off-field”

Earthworm,

Eisenia fetida 4.0 2.38 0.009 423


threatened species

1 No crop interception is included in the Tier I calculations. Assumes application to bare soil.

Risks to soil organisms were below the level of concern with the exception of the chronic risks to

threatened soil organisms for the active ingredient mefentrifluconazole following application of

Revystar® Fungicide in-field.

Due to the risk identified for threatened earthworm species in-field, chronic TER values were refined,

taking into account interception by the crop. A crop interception value of 80% was applied

(corresponding to the growth stage BBCH 30-39, which is the earliest growth stage that the substance

will be applied as clarified by the applicant).

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Table 38: Chronic TER values for soil organisms (Tier II1)

Species

NOEC

(mg/kg

soil)

Drift (%)

PEC

(mg/kg

soil)

TER

chronic Conclusion

Scenario – mefentrifluconazole, two applications to cereals at 30 g/ha (150 g ai/ha with 80% crop

interception) – “in-field”

Earthworm,

Eisenia fetida 4.0 NA 0.08 50


threatened species

1 Crop interception is included in the Tier II calculations, assuming that a proportion of the applied fungicide will

be intercepted by the crop and remain on the foliage rather reach the soil

The chronic TER for threatened species in-field is below the LOC, taking into account a realistic crop

interception value of 80%.

The applicant has provided the argument that there are 179 taxa or earthworms in New Zealand with

only one species reported as “at risk - declining” (Deinodrilus gorgon) and 31 reported as “at risk -

naturally uncommon” (Department Of Conservation (DOC) 2014). Despite a potentially large

distribution area for this earthworm species on the West Coast, the best documented natural habitat is

not threatened by agriculture but rather by on-going and future mining activities on the Stockton and

Denniston Plateaus. Furthermore, Deinodrilus gorgon is reported have a total area of occupancy

≤1000 ha (10 km2) in New Zealand. The other 31 species ranked as “naturally uncommon” are

predominantly endemic to New Zealand. These 32 earthworm species are confined to a specific

forestry areas or occur within naturally small and widely scattered populations, where this distribution

is not the result of human disturbance.

A recent survey (Kim Y. 2017) sampled earthworms on the South Island including several locations in

the Canterbury region, which is a main wheat and barley growing area in New Zealand. Samples

collected from agricultural land found only native earthworm species classified as “not threatened”

and/or earthworm species exotic to New Zealand. The additional lines of scientific evidence provided

by Buckley et al. (Department Of Conservation (DOC) 2014) and Kim et al. (Kim Y. 2017) indicate

threatened species of earthworms in New Zealand are unlikely to be exposed to Revystar®

Fungicide.

The NZ EPA accepts this argument and agrees that threatened species of earthworm identified in

New Zealand are unlikely to be exposed to Revystar Fungicide in-field.

Soil microorganisms

For mefentrifluconazole the data indicate that there are no effects on the nitrogen and carbon

transformation in a field soil test concentration of 2.53 mg ai/kg soil dry weight (highest concentration

tested). The PEC calculated in the earthworm risk assessment is 0.4 kg ai/kg soil which is far below

the NOEC for soil microorganisms. As such, there is no risk to soil microorganisms following use of

Revystar Fungicide.

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Soil accumulation

Mefentrifluconazole was determined to be persistent in soil and therefore the accumulation of the

active ingredient in soil over time was evaluated. The PEC calculator (v. 1.0) developed by the UK

regulator was used and the accumulation according to the Good Agricultural Practises (GAP) for a

period of 20 years was considered. The input parameters and results of the modelling are displayed in

Table 39. Corresponding acute and chronic TER values are shown in Table 40 and Table 41,

respectively.

Table 39: Input parameters for PEC soil accumulation and resulting PAC1 values

Input parameters Mefentrifluconazole

Soil depth 5 cm

Soil density 1.5 g cm3

Application rate (kg ai/ha) 0.150

Number of applications 2

Application interval 21 days

Soil DT50 (lab) ≥1000 days

Crop interception 0% (Tier I) 80% (Tier II)

PAC1 value – steady state (mg/kg) 1.765 0.353

PAC1 value – peak (mg/kg) 1.388 0.278

1 Predicted Accumulation Concentration (PAC)

Table 40: Acute TER values for soil organisms (Tier I1) – soil accumulation

Species LC50

(mg/kg soil)

PAC (mg/kg

soil) TER (acute) Conclusion

Earthworm,

Eisenia fetida >500

1.765

(peak) 360


threatened species

Earthworm,

Eisenia fetida >500

1.388

(steady state) 283


threatened species

1 No crop interception is included in the Tier I calculations. Assumes application to bare soil.

Table 41: Chronic TER values for soil organisms – soil accumulation

Species NOEC

(mg/kg soil)

PAC (mg/kg

soil)

TER

(chronic) Conclusion

Tier I (0% crop interception)

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Species NOEC

(mg/kg soil)

PAC (mg/kg

soil)

TER

(chronic) Conclusion

Earthworm,

Eisenia fetida 4.0

1.765

(peak) 2.88

Above LOC for threatened/non-

threatened species

Earthworm,

Eisenia fetida 4.0

1.388

(steady state) 2.27

Above LOC for threatened/non-

threatened species

Tier II (80% crop interception)

Earthworm,

Eisenia fetida 4.0 0.353 (peak) 14.39


species


species

Earthworm,

Eisenia fetida 4.0

0.278

(steady state) 11.33


species


species

Both the highest exposure concentration (peak PAC) and steady state PAC values were used to

calculate the TER values for acute and chronic exposure to earthworms. The acute TER values were

below the level of concern for both non-threatened and threatened species. At Tier I (assuming 0%

crop interception), chronic risks to earthworms were above the level of concern for both non-

threatened and threatened species.



only for threatened species, which as described above are unlikely to be exposed to Revystar®

Fungicide in-field.

Conclusions of the soil organism risk assessment



off-field.


Revystar® Fungicide are above the LOC for threatened species in-field. TERs were below the LOC

for non-threatened species in-field, as well as for off-field for both non-threatened and threatened

species. Due to the risk identified for threatened earthworm species in-field, chronic TER values were

refined, taking into account interception by the crop (80%). The chronic TER for threatened species

in-field is still above the LOC however. Further evaluation indicated that threatened species are

unlikely present in the application areas of Revystar® Fungicide as a result the risk is considered to

be below the LOC.



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field.

Non-target plant risk assessment

The non-target plant risk assessment is based on a comparison of the PEC with toxicity values for the

substance. Depending on the type of data provided, for non-threatened plants a TER or an RQ is

calculated (a TER is used when an EC50 is available, an RQ is used when an EC25 is available). For

threatened non-target plants an RQ is calculated by comparing the PEC with a NOEC. The different

levels of concern assigned to specific TER/RQ values are listed in the EPA standard risk assessment

methodology (EPA 2018).

RQ values for non-threatened non-target plants are shown in Table 43. TER values for threatened

non-target plants are shown in Table 42. No crop interception was incorporated in the risk

assessment.

Table 42: RQ value for non-target plant – edge of field

Scenarios

Exposure

(g ai/ha) *

drift factor

* MAF1

EC25

(g ai/ha) RQ Conclusion

Revystar® Fungicide – 150 g ai/ha, two applications

Cereals 6.78 >1502 0.045 Below LOC for non-threatened

species

1 Drift factor is 2.38%, a worst-case MAF of 1.9 was used

2 Toxicity endpoint is the same for vegetative vigour and seedling emergence

Table 43: RQ value for threatened non-target plants

Scenarios

Exposure

(g ai/ha) *

drift factor*

MAF11

NOEC

(g ai/ha) RQ Conclusion

Revystar® Fungicide – 150 g ai/ha, two applications

Cereals 6.78 752 0.090 Below LOC for threatened species

1 Drift factor is 2.38%, a worst-case MAF of 1.9 was used

2 Lowest toxicity endpoint used as worst-case (seedling emergence). This endpoint should be treated with caution however since there is some uncertainty in derivation of this endpoint.

Conclusion for non-target plant risk assessment

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as the formulated product Revystar® Fungicide are below the level of concern.

Bird risk assessment

The bird risk assessment is based on a comparison of the PEC with toxicity values for the substance.

The toxicity value is divided by the PEC to give a Toxicity Exposure Ratio (TER). The different levels

of concern assigned to specific TER values are listed in the EPA standard risk assessment

methodology (EPA 2018).

Screening assessment

Predicted exposure to mefentrifluconazole under the bird acute dietary and reproduction screening

assessments is shown in Table 44.

Table 44: Exposure of birds for acute and reproduction screening assessments

Screening

type1

Indicator

species2

Application

rate

(kg/ha)

Short-

cut

value

(90th%)3

TWA4

MAF

(90th

%)5

No of

applications DDD

Cereals, two applications, 21-day spray interval

Acute

Small

omnivorous

bird

0.15 158.8 NA 1.1 2 26.20

Reproduction

Small

omnivorous

bird

0.15 64.8 0.53 1.2 2 6.18

1 EFSA (EFSA 2009), Table 5 p27 2 EFSA, (EFSA 2009), Table 6 p28 3 90th %ile short-cut value used for the acute assessment, mean value used for the reproduction assessment. EFSA,

(EFSA 2009), Table 6 p28 4 The exposure assessment of the reproduction assessment uses time-weighted average (TWA) exposure estimates

over 1, 2, 3 or 21 days for different phases of the assessment. 1 day = 1.0; 2 days = 0.93; 3 days = 0.9; 21 days = 0.53. EFSA, (EFSA 2009), Table 11 p34.

5 90th %ile MAF value used for the acute assessment, mean value used for the reproduction assessment. EFSA, (EFSA 2009), Table 7 p29

Calculation of TERs

TER calculations for the acute dietary and reproductive risk assessment are detailed in Table 45.

Table 45: TER values for acute dietary risk assessment (TWA = 0.53)

Crops &

BBCH class

Generic

focal

species1

Daily

dietary

dose

(DDD)

Toxicity

endpoint

value (mg/kg

bw/d)*

TER ratio Conclusion

Application rate (kg/ha) – Number of applications

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Crops &

BBCH class

Generic

focal

species1

Daily

dietary

dose

(DDD)

Toxicity

endpoint

value (mg/kg

bw/d)*


Acute Small

omnivorous

bird

26.20 816 31.1 Risks below LOC for

threatened and non-

threatened species

Reproduction Small

omnivorous

bird

6.18 25.3 4.1 Risks above LOC

for non-threatened

and threatened

species

Conclusions of the bird screening risk assessment

The acute screening risk assessment indicates an acute risk below the level of concern to birds from

mefentrifluconazole from the use of Revystar® Fungicide. In the reproductive screening assessment

the TER values indicate a chronic risk above the level of concern to birds. As risks were above the

level of concern a Tier 1 risk assessment for chronic toxicity was performed.

Tier 1 assessment

Tier 1 uses the same general approach as the screening assessment but requires more specific

exposure scenarios. More details are provided in the EPA standard risk assessment methodology

(EPA 2018).

For each generic focal species the daily dietary dose (DDD) is presented in Table 44 (acute and

chronic).

The toxicity figures are the same than those considered in the screening assessment.

The indicator species mentioned in Table 46 (chronic) are not real species but have to be considered

as representative of groups of birds of the same size and same feeding behaviour.

Table 46: TER values for chronic risk assessment – Tier 1 assessment

Crops &

BBCH

class

Focal species

Short-

cut

value2

(90th %)

Toxicity

endpoint

(mg/kg

bw)


Mefentrifluconazole – Cereals, 150 g ai/ha, two applications, 21-day spray interval

BBCH 10 -

29

Small omnivorous bird “lark”.

Combination (invertebrates

with interception (25% crop

leaves, 25% weed seeds,

50% ground arthropods

10.9

25.3

24.3

Below the LOC for

non-threatened and

threatened species

BBCH 30 -

39

Small omnivorous bird “lark”.


5.4 49.1

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BBCH ≥ 40 Small omnivorous bird “lark”.





3.3 80.4

Early

(shoots)

autumn-

winter

BBCH 10-29

Large herbivorous bird

"goose" Grass + cereals

100% cereal shoots

16.2 16.4

Late post-

emergence

(May-

June)BBCH

71-89

Small insectivorous bird

"passerine". Foliar insects,

100% foliar insects

22.4 11.8

Late

season-

Seed heads

Small

granivorous/insectivorous

bird “bunting” Grains/ear

100% cereal seeds

12.5 21.2

Conclusion for bird risk assessment (Tier 1)

The chronic Tier 1 risk assessment indicates risks below the level of concern to both threatened and

non-threatened birds from the use of Revystar® Fungicide.

Secondary poisoning

Given the criteria under the HSNO Act the active ingredient mefentrifluconazole is not considered to

be bioaccumulative (BCF <500). Therefore, no risk assessment via secondary poisoning is

performed.

Conclusions for bird risk assessment



negligible. In the reproductive screening assessment, the TER values indicate a chronic risk above

the LOC to non-threatened and threatened bird species. After the Tier I risk assessment, risks to non-


poisoning is considered to be low.

Pollinator risk assessment

The basis for the pollinator risk assessment is a comparison of the environmental exposure

concentration (EEC) with toxicity endpoints to which safety factors have been applied. The EEC is

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divided by the toxicity endpoint to calculate a risk quotient (RQ) value. The methodology for the

pollinator risk assessment, including the level of concern (LOC) ascribed to specific RQ values, is

described in detail in the EPA standard risk assessment methodology (EPA 2018). The results of the

bee risk assessment are shown in Table 47.

Table 47: Bee exposure estimates and RQ values

Use scenario Application

rate (kg ai/ha)

EEC (µg

ai/bee)

Toxicity

endpoint

value (µg

ai/bee)

RQ Conclusion

Acute / Adult bees – contact

Cereals 0.15 0.36 >100 <0.0036 Below the LOC

Acute / Adult bees – oral

Cereals 0.15 4.29 >100 <0.04 Below the LOC

Chronic / Adult bees – oral

Cereals 0.15 4.29 110.5 0.04 Below the LOC

Acute / Larvae bees – oral

Cereals 0.15 1.96 43.9 0.04 Below the LOC

Conclusions of the pollinator risk assessment

The risks to pollinators are below the LOC and any risks are negligible.

Non-target arthropod risk assessment

The non-target arthropod risk assessment is a comparison of the predicted environmental

concentration (PEC) with toxicity endpoints to which safety factors have been applied. The PEC is

divided by the toxicity endpoint to calculate a hazard quotient (HQ) value. The methodology for the

pollinator risk assessment, including the level of concern (LOC) ascribed to specific HQ values, is

described in detail in the EPA standard risk assessment methodology (EPA 2018).

Results of the Tier I in-field and off-field non-target arthropod risk assessment are shown in Table 48

and Table 49, respectively.

Table 48: In-field HQ values for non-target arthropods (Tier I)

Species LR50

(g ai/ha)

Application rate

(g ai/ha) MAF

Hazard

Quotient Conclusion

Parasitic wasp, Aphidius

rhopalosiphi 0.954 150 1.7 267 Above the LOC

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Species LR50

(g ai/ha)

Application rate

(g ai/ha) MAF

Hazard

Quotient Conclusion

Predatory mite,

Typhlodromus pyri 7.691 150 1.7 33 Above the LOC

Table 49: Off-field HQ values for non-target arthropods (Tier I) [drift factor = 2.77%1]

Species LR50

(g ai/ha)

Application rate

(g ai/ha) MAF

Hazard

Quotient Conclusion


rhopalosiphi 0.954 150 1.7 6.36 Above the LOC

Predatory mite,

Typhlodromus pyri 7.691 150 1.7 0.79 Below the LOC

1 BBA drift value for two applications to field crops (1 m)

At Tier I all hazard quotients were above the level of concern (LOC) with the exception of the off-field

hazard quotient for the predatory mite (Typhlodromus pyri). As such, a Tier II non-target arthropod

risk assessment was performed. Results of the Tier II in-field and off-field non-target arthropod risk

assessment are shown in Table 50 and Table 51, respectively.

Table 50: In-field HQ values for non-target arthropods (Tier II)

Species LR50

(g ai/ha)

Application rate

(g ai/ha) MAF

Hazard

Quotient Conclusion


rhopalosiphi >300 150 1.7 <0.85 Below the LOC

Predatory mite,

Typhlodromus pyri >300 150 1.7 <0.85 Below the LOC

Table 51: Off-field HQ values for non-target arthropods (Tier II) [drift factor = 2.77%1]

Species LR50

(g ai/ha)

Application rate

(g ai/ha) MAF

Hazard

Quotient Conclusion


rhopalosiphi >300 150 1.7 <0.020 Below the LOC

Predatory mite,

Typhlodromus pyri >300 150 1.7 <0.020 Below the LOC

1 BBA drift value for two applications to field crops (1 m)

Conclusion for non-target arthropod risk assessments

Risks to non-target arthropods are below the LOC for both off-field and in-field at Tier II.

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Conclusions of the ecological risk assessment

The EPA staff assessed the potential risk to be triggered by the use of Revystar® Fungicide following

the instructions captured in the proposed label and GAP table.

Aquatic risk assessment

Predicted exposures concentrations of mefentrifluconazole, applied as the formulated product

Revystar® Fungicide resulted in calculated RQs above the LOC for the aquatic environment. Chronic

risks to threatened species of aquatic invertebrates were identified for both ground-based (RQ = 0.27,

LOC = 0.1) and aerial applications (RQ = 0.32, LOC = 0.1). A refinement of the soil DT50 did not result

in risk below the level of concern in the screening step. The following controls are proposed to reduce

exposures below the level of concern:

Use restrictions

The maximum application rate is 150 g mefentrifluconazole/ha, maximum two

applications/year, and a minimum interval between applications of 21 days

Apply with ground-based equipment and minimum medium droplets, as defined by the

American Society of Agricultural and Biological Engineers ASABE Standard (S572) or the

British Crop Production Council guideline. This information should be required on the

label so that users are aware of this control.

For aerial application, use minimum coarse droplets, as defined by the American Society

of Agricultural and Biological Engineers ASABE Standard (S572) or the British Crop

Production Council guideline. This information should be required on the label so that

users are aware of this control.

A label statement indicating: “DO NOT apply when wind speeds are less than 3 km/hr or

more than 20 km/hr as measured at the application site”.

Groundwater risk assessment



groundwater are considered below the level of concern.

Sediment risk assessment





for Chironomus riparius). The NOEC determined in this case was the highest concentration tested,

and no significant effects were observed at this concentration. If a higher concentration had been

tested, the NOEC could potentially be higher, thus resulting in a lower risk.

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or non-target arthropods), and other regulators (EFSA) concluded that risks to sediment-dwelling

organisms were low, risks to sediment-dwelling organisms are considered to be low.

Soil organism risk assessment



off-field.


Revystar® Fungicide are above the LOC for threatened species in-field. TERs were below the LOC

for non-threatened species in-field, as well as for off-field for both non-threatened and threatened

species. Due to the risk identified for threatened earthworm species in-field, chronic TER values were

refined, taking into account interception by the crop (80%). The chronic TER for threatened species

in-field is still above the LOC however. Further evaluation indicated that threatened species are

unlikely present in the application areas of Revystar® Fungicide as a result the risk is considered to

be below the LOC.







field.

Non-target plant risk assessment


as the formulated product Revystar® Fungicide are below the level of concern.

Bird risk assessment



negligible. In the reproductive screening assessment, the TER values indicate a chronic risk above

the LOC to non-threatened and threatened bird species. After the Tier I risk assessment, risks to non-


poisoning is considered to be low.

Pollinator risk assessment

The risks to pollinators are below the LOC and any risks are negligible.

Non-target arthropod risk assessments

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Risks to non-target arthropods are below the LOC for both off-field and in-field.


acceptable with the proposed controls.

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Appendix I: Proposed controls

Prescribed controls

The hazard classifications of Revystar determine a set of prescribed controls specified by the EPA

Notices. There are also requirements in the Health and Safety at Work (HSW) (Hazardous

Substance) Regulations.

The Hazardous Substances Labelling, Safety Data Sheet (SDS), Packaging, Disposal and Hazardous

Property Controls (HPC) Notices 2017 apply to Revystar.

Exposure thresholds

Exposure thresholds proposed for mefetrifluconazole are shown in Table 52. Acceptable Daily

Exposure (ADE) and Potential Daily Exposure (PDE) values are not controls as such, but are health

based exposure guidance values which can be used to inform risk assessments as well as the setting

of controls, such as Maximum Residue Levels under the ACVM Act.

The EPA has reviewed health based exposure guidance values established by overseas regulators

(shown in Table 53) to inform the selection of ADE and PDE values for mefetrifluconazole

Table 52: Derivation of appropriate health-based exposure guidance value for

mefetrifluconazole

Available

international

toxicological

thresholds

Key Systemic

effect

NOAEL

(mg/kg

bw/day)

Uncertainty

factors

Value

(mg/kg

bw/day)

Modifications Remarks

EFSA (EFSA

2018) -ADI

No treatment

related changes

were observed

at the NOAEL

Not carcinogenic

in mice

3.5 100 0.035 None

18-month

dietary chronic

toxicity/carcinog

enicity study:

mice

Based on the assessment of the available data, the following Acceptable Daily Exposure (ADE),

Potential Daily Exposure (PDE) and Acute reference dose (ARfD) values have been provided (see

Table 27).

No Tolerable Exposure Limit (TEL) value has been set for this substance. This is because it is not

considered that exposure is likely to result in an appreciable toxic effect based on the quantitative risk

assessment done here.

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Table 53: exposure thresholds for mefentrifluconazole

Active Ingredient ADE PDE ARfD TEL

mefentrifluconazole, 0.035 mg/kg

bw/d (EFSA)

PDE (Food) =

0.025 mg/kg

bw/d

PDE (Drinking water)

= 0.007 mg/kg

bw/d

PDE (Other) =

0.0035 mg/kg

bw/d

0.15 mg/kg bw/d Not set at this

time

Impurity limits

The following limits as shown in Table 54 are set for toxicologically relevant impurities in

mefentrifluconazole based on the European Commission specification (EC 2019).

Table 54: Impurities limits proposed for Revystar

Active ingredient Impurity and maximum limits (mg/kg) Source/ specification

(FAO/APVMA/NZ EPA)

mefentrifluconazole

N,N-dimethylformamide (DMF; 68-12-2) : 0.5 g/kg

toluene (108-88-3) : 1 g/kg

1,2,4-(1H)-triazole (288-88-0): 1 g/kg

European Commission

(EC 2019)

Ecotoxicity controls

Application restrictions

A maximum application rate is proposed to be set for Revystar, as shown in Table 55.

Table 55: Maximum application rates for Revystar

Active component Maximum application rate

Mefentrifluconazole 150 g ai/ha, maximum 2 application/year, interval between application 21 days

Fluxapyroxad 75 g ai/ha, maximum 2 application/year, interval between application 21 days

Application method

Revystar must not be applied when wind speeds are less than 3 km/hr or more than 20 km/hr as

measured at the application site.

Apply with ground-based equipment and minimum medium droplets, as defined by the American

Society of Agricultural and Biological Engineers ASABE Standard (S572) or the British Crop

Production Council guideline. This information should be required on the label so that users are aware

of this control

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For aerial application, use minimum coarse droplets, as defined by the American Society of

Agricultural and Biological Engineers ASABE Standard (S572) or the British Crop Production Council

guideline. This information should be required on the label so that users are aware of this control

Buffer zones

None identified

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Appendix J: Study summaries

Manufacturer code name for mefentrifluconazole is BAS 750 F.

Manufacturer code name for Revystar® Fungicide is BAS 752 00 F.

Toxicity study summaries

Mammalian toxicity studies on mefentrifluconazole and Revystar® Fungicide have been reviewed.

These studies are used to describe potential risks to human health. The effects on mammals in these

studies are used as proxies for the impact on humans. Data from the studies have been used for

classifying the active ingredient and the formulated substance and for derivation of appropriate health-

based criteria which are used in risk assessment. Data summaries for mefentrifluconazole can be

found in the European Commission Draft Assessment Report (EC 2017) Volume 3 – B.6 (AS). Data

summaries for Revystar® are provided in Table 56 to Table 62.

Mammalian toxicology - Robust study summaries for Revystar®

Acute toxicity [6.1]

Table 56: Acute Oral Toxicity [6.1 (oral)]

Type of study Acute oral lethality

Flag Key study

Test Substance BAS 752 00 F ; Batch: FD-140205-0020; BAS 750 F: 100.5 g/L; BAS

700 F: 52.5 g/L

Endpoint LD50

Value >300 mg/kg LD50 <2000 mg/kg

Reference

2014). BAS 752 00 F - Acute oral toxicity study in rats.

:

Klimisch Score 1

Amendments/Deviations None of significance

GLP Yes

Test Guideline/s OECD 423; Commission Regulation (EC) No 440/2008; US EPA

OPPTS 870.1100

Species Rat

Strain Wistar, Crl:WI (Han) SPF

No/Sex/Group 2000 mg/kg bw in 3 F, 300 mg/kg bw in 6 F (2 groups of 3)

Dose Levels 300 and 2000 mg/kg

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Exposure Type Oral gavage

Study Summary

2000 mg/kg (single test group):

Two animals were sacrificed in a moribund state after 5 hours. Clinical

signs consisted of: impaired general state (3/3), poor general state (2/3),

dyspnoea (3/3), gasping (2/3), flat respiration (2/3), piloerection (3/3),

cowering (1/3), abdominal position (2/3), and staggering (2/3) in two

animals.

Macroscopic pathological findings in the two animals that were

sacrificed moribund consisted of a red discoloration and thickening of

the glandular stomach.

300 mg/kg (first test group):

No mortality occurred. An Impaired general state and pilo-erection was

observed in all animals

300 mg/kg (second test group):

No mortality or clinical signs were observed.

There were no macroscopic pathological findings in the surviving

animals sacrificed at the end of the observation period (all doses).

The mean body weight of the surviving animal in the 2000mg/kg bw test

group increased within the normal range throughout the study period.

The body weight of one animal each in both 300 mg/kg bw test groups

increased within the normal range throughout the study period, while the

two other animals in each test group showed stagnation of body weight

during the second observation week.

Additional Comments No additional comments

Conclusion The LD50 was greater than 300 mg/kg bw but less than 2000 mg/kg bw.

Accordingly, the substance is classified as 6.1D.

Table 57: Acute Dermal Toxicity [6.1 (dermal)]

Type of study Acute dermal lethality

Flag Key study


700 F: 52.5 g/L

Endpoint LD50

Value >5000 mg/kg

Reference

(2014). “BAS 752 00 F - Acute dermal

toxicity study in rats.”

Klimisch Score 1

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GLP Yes


OPPTS 870.1200

Species Rat

Strain Wistar, Crl:WI (Han) SPF

No/Sex/Group 5/sex/group

Dose Levels 5000 mg/kg

Exposure Type Dermal under a semi-occlusive wrap

Study Summary

No mortality, signs of systemic toxicity, or local skin effects were

observed.

The mean body weight of the male animals increased within the normal

range throughout the study period.

The body weight of the female animals increased within the normal

range throughout the study period with two exceptions in which a

stagnation of body weight occurred during the first week. Body weights

were within the normal range during the second week.

No macroscopic pathologic abnormalities were noted in any animal at

study termination.


Conclusion The LD50 was greater than 5000 mg/kg. Accordingly, the substance is

not classified.

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Table 58: Acute Inhalation Toxicity [6.1 (inhalation)]

Type of study Acute inhalation lethality

Flag Key study


700 F: 52.5 g/L

Endpoint LC50

Value >1.9 mg/L LC50 <5.1 mg/L

Reference

2014). “BAS 752 00 F: 4-Hour Acute Inhalation Toxicity

Study in the Rat.”

Klimisch Score 1


GLP Yes

Test Guideline/s OECD 403; Commission Regulation (EC) No 1907/2006 and 440/2008;

US EPA OPPTS 870.1300

Species Rat

Strain RccHan: WIST(SPF)

No/Sex/Group 5/sex/group

Dose Levels

0.9 mg/L; MMAD / GSD (mean): 2.76 μm / 3.29



Exposure Type Nose only

Study summary

All animals exposed to 5.1 mg/L air spontaneously died or were

sacrificed in extremis on the day of exposure. All animals exposed to 0.9

or 1.9 mg/L air survived the scheduled observation period.

Clinical signs observed prior to death consisted of swaying gait, apathy,

prostration, ruffled fur, laboured breathing, breathing noises and

salivation.

Principal signs of toxicity observed after exposure to 1.9 or 0.9 mg/L air

consisted of decreased activity, hunched posture, ruffled fur, and

salivation. These generally receded within the first week after exposure.

Laboured breathing and breathing noises were observed during the first

and second week after exposure and persisted until the end of the

observation period.

Body weight loss or stagnation of body weight gain was observed

between test days 1 and 4 in all animals exposed to 1.9 mg/L air. Two

males additionally showed body weight loss or stagnation of body weight

gain at isolated measurement intervals after test day 4.

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Body weight loss was observed between test days 1 and 2 in all animals

exposed to 0.9 mg/L air and body weight loss or stagnation of body

weight gain continued until test day 4 in 4/5 males and 3/5 females.

Thereafter, normal body weight gain was observed in all animals

exposed to 0.9 mg/L air.

At necropsy, all animals exposed to 5.1 mg/L air showed reddish or

dark-brown discoloration of the lungs. No macroscopic findings were

present at necropsy in the animals exposed to 0.9 or 1.9 mg/L.


Conclusion The LC50 is greater than 1.9 mg/L but less than 5.1 mg/L. Accordingly,

the substance is classified as 6.1D.

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Table 59: Skin Irritation [6.3/8.2]

Type of study Primary skin irritation/corrosion

Flag Key study


700 F: 52.5 g/L

Endpoint Mean Draize score for erythema and oedema

Value Mean score - Erythema: 3.0, Oedema: 1.6

Reference

(2014). “BAS 752 00 F - Acute dermal

irritation / corrosion in rabbits.”

Klimisch Score 1


GLP Yes


OPPTS 870.2500

Species Rabbit

Strain New Zealand White: Hsdlf; NZW (SPF)

No/Sex/Group 3 F

Dose Levels 0.5 mL

Exposure Type Dermal under semi-occlusive dressing

Study Summary

The following test item-related clinical observations were recorded

during the course of the study: very slight to moderate erythema (grade

1 to 3); very slight to slight oedema (grade 1 to 2), and scaling.

The cutaneous reactions eventually decreased in severity but were not

fully reversible in all animals within the 14-day observation period after

removal of the patch (study termination). In two animals, well-defined

erythema (grade 2), very slight oedema (grade 1) and scaling were still

noted; while the third animal showed very slight erythema (grade 1) and

scaling on day 14.

Mean scores over 24, 48 and 72 hours for all three animals were 3.0 for

erythema and 1.6 for oedema.


Conclusion

The mean scores over 24, 48 and 72 hours for all three animals were

3.0 for erythema and 1.6 for oedema. Accordingly, the substance is

classified as 6.3A for skin irritation.

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Table 60: Eye Irritation [6.4/8.3]

Type of study Eye irritation/corrosion

Flag Key study


700 F: 52.5 g/L

Endpoint

Mean Draize score for cornea, conjunctiva (redness and chemosis), and

iris

Value

Mean Draize Score -

Cornea

-Opacity: 1.0

Conjunctiva

-Redness: 1.6

-Chemosis: 1.1

Iris: 0.6

Reference

(2014). “BAS 752 00 F - Acute eye

irritation in rabbits.”

2015. “BAS 752 00 F - Acute eye irritation in rabbits.”

,

Klimisch Score 1


GLP Yes


OPPTS 870.2400

Species Rabbit

Strain New Zealand White: Hsdlf; NZW (SPF)

No/Sex/Group 3 F

Dose Levels 0.1 mL

Exposure Type Direct ocular instillation

Study Summary

Ocular reactions were assessed approximately 1, 24, 48 and 72 hours

after application and on study Day 7. Additional eye examinations were

performed from hour 24 until study day 7 after application with the

instillation of a fluorescein solution. Due to a negative finding on study

day 7 (no corneal lesions detectable with fluorescein) and the observed

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reversibility of ocular reactions in all animals the study was terminated

on study day 7.

The following observations were recorded during the course of the

study: slight to moderate corneal opacity (grade 1-2); moderate iritis

(grade 1); slight to severe conjunctival redness (grade 1-3); slight to

moderate conjunctival chemosis (grade 1-2); slight to obvious discharge

(grade 1-2); desquamation of corneal epithelium and contracted pupil

was noticed from hour 48 until hour 72 after application. Injected scleral

vessels in a circumscribed or circular area were observed from hour 1

until study day 7 at the latest. Corneal lesions detectable with the aid of

fluorescein grade 1- 4 (i.e. affected area) were seen from hour 24 until

hour 72.

The ocular reactions were reversible in all animals within 7 days after

application.

Mean scores calculated for each animal over 24, 48 and 72 hours were

1.3, 0.7 and 1.0 for corneal opacity, 1.0, 0.7 and 0.0 for iris lesions, 2.7,

1.0 and 1.0 for redness of the conjunctiva and 2.0, 0.7 and 0.7 for

chemosis.


Conclusion

The mean scores over 24, 48 and 72 hours for all three animals were

1.0 for corneal opacity, 1.6 and 1.1 for conjunctival redness and

chemosis respectively, and 1.1 for iritis. Accordingly, the substance is

classified as 6.4A for eye irritation.

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Table 61: Contact Sensitisation [6.5]

Type of study Primary skin sensitisation – local lymph node assay

Flag Key study


700 F: 52.5 g/L

Endpoint Stimulation index (SI)

Value SI: 4.06 with 25% w/w; EC3 = 19.6%

Reference

(2014). “BAS 752 00 F – Skin Sensitisation: Local Lymph

Node Assay.”

.:

Klimisch Score 1


GLP Yes

Test Guideline/s OECD 429; Commission Regulation (EC) No. 440/2008, B.42

Species Mouse

Strain CBA/CaOlaHsd

No/Sex/Group 5 F / 4 groups

Dose Levels Vehicle control, 5, 10, and 25% (w/w)

Exposure Type Topical application (25 µL) on the ear dorsum

Study Summary

The animals did not show any signs of systemic toxicity during the

course of the study and no cases of mortality were observed. The

animals treated with a test item concentration of 10 and 25% showed an

erythema of the ear skin (score 1 and 2). Animals treated with 5% test

item concentration did not show any signs of local skin irritation. In the

group treated with a test item concentration of 25%, a statistically

significant increase in ear weights was observed in comparison to the

values of the vehicle control group. For BALB/c mice, a cut-off value of

1.1 for the ear weight index was reported for a positive response

regarding ear skin irritation. The index determined for the high dose

group just reached this threshold (index of 1.10), thus indicating a slight

irritant property of the test item. Nevertheless, the threshold value of

25% increase in ear weights for excessive local skin irritation mentioned

in OECD guideline 429 was not exceeded in any group.

Stimulation Indices (SI) of 0.89, 1.10, and 4.06 were determined with the

test item at concentrations of 5, 10, and 25% in acetone/olive oil (4+1,

v/v), respectively. A dose response was observed and an EC3 value of

19.6 % was derived.

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Additional Comments

A score of 4.06 is just above the cut-off value of 3 and the fact there was

evidence of irritation which could also add to the SI value indicates the

material is likely a very weak sensitiser.

Conclusion The test substance was determined to have contact sensitisation

potential based on a SI >3 at 25% w/w and is accordingly labelled 6.5B

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Dermal Absorption of Mefentrifluconazole (BAS 750 F) in Revystar® (BAS 752 00 F)

Table 62: Dermal Absorption – In Vitro

Study type In vitro dermal absorption through human skin

Flag Key study

Test Substance

Carbon-14 labelled BAS 750 F (mefentrifluconazole), Batch: 1062-2001;

Specific activity: 5.46 MBq/mg; Radiochemical purity: >98%; Non-

radiolabelled material test item Name: BAS 750 F; Batch: COD-001880;

Purity: 98.6%, and BAS 752 00 F; Batch: FD-140205-0020; BAS 750 F:

100.5 g/L; BAS 700 F: 52.5 g/L; Vehicle: Diluted with water

Endpoint Absorption kinetics

Value

Concentration Absorption %

1000 µg/cm2 / 100 mg/ml (concentrate) 0.36 ± 0.26

5.0 µg/cm2 / 0.50 mg/ml (1:200 dilution) 2.82 ± 0.98

Reference

(2014). “14C-BAS 750 F in BAS 752 00 F

Study of penetration through human skin in vitro.”

Klimisch Score 1


GLP Yes

Test Guideline OECD 428 and OECD Guidance Document No. 28 for the Conduct of Skin

Absorption Studies.

Species Human

Strain NA

No/Sex/Group 8 (abdominal)

Dose Levels Concentrated active: 1000 µg/cm2 / 100 mg/ml

1:200 dilution: 5.0 µg/cm2 / 0.5 mg/ml

Exposure Type In vitro using flow-through diffusion chambers in static mode

Study Summary

Split-thickness human skin membranes were mounted into Franz-type flow

through diffusion cells operated in static mode. The skin surface

temperature was maintained at 32°C ± 1°C throughout the experiment.

The integrity of the skin preparation was determined by measuring its trans

epidermal electrical resistance (TEER).

Absorption of [14C]-750 F was assessed by collecting receptor fluid at 1, 2,

4, 6, 8, 12, and 24 hours post dose. At 24 h post dose, the underside of

the skin was rinsed with receptor fluid (receptor rinse). The skin was

removed from the cells and dried with a tissue swab. The cell was

dismantled and the donor chamber and receptor chamber were retained

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separately for analysis. The stratum corneum was removed by tape

stripping and the skin divided into exposed and unexposed skin.

100 mg/mL: At 24 h post dose, the total recovery was 96.64% of the

applied dose. The stratum corneum retained 0.24% of the applied dose

and the total unabsorbed dose was 96.04% of the applied dose. The total

absorbed dose was 0.36 ± 0.26%.

0.5 mg/mL: At 24 h post dose, the total recovery was 98.45% of the

applied dose. The stratum corneum retained 1.21% of the applied dose

and the total unabsorbed dose was 94.41% of the applied dose. The total

absorbed dose was 2.82 ± 0.98%.

Additional Comments Values used in the risk assessment were the same as those suggested by

the applicant.

Conclusion

The results of this study indicate mefentrifluconazole in Revystar® is

poorly absorbed (0.36 ± 0.26%) through the skin as a concentrate (100

mg/mL) and when diluted 1:200 with water (0.5 mg/ml) into an in-use spray

dilution (2.82 ± 0.98%). Due to variation in the data the values used in the

risk assessment were the average plus one SD and rounded up to 1% for

the concentrate and 4% for the dilution.

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Environmental fate studies



metabolites were sourced from the mefentrifluconazole DAR unless otherwise stated. Study

summaries have only been included in Appendix J where there are comments in regard to individual

studies, and are provided in Table 63 to Table 70

Abiotic degradation

Table 63: Photodegradation in soil (photolysis): active ingredient (key study)

Study type Soil photolysis

Flag Key study

Test Substance BAS 750 F (mefentrifluconazole)

Endpoint DT50

Value 93 days (chlorophenyl-label) and 170 days (triazole-label)

Reference (3.6.5) Hassink and Delgado (2014a). Soil photolysis of BAS 750 F. BASF Study

Identification Number: 433829. BASF Registration Document Number (Doc

ID): 2014/1181666.

Study Summary The summary in the Draft Assessment Report (DAR) – BAS 750F – Volume 3

– Annex B.8 (AS) Environmental fate and behaviour (2017) is fully accepted

by the EPA Staff.

Comments The determined DT50 values indicate that the degradation rate of BAS 750 F

under irradiated conditions is faster than in the dark control, thus BAS 750 F

may undergo photolysis in soil although at a very slow rate. It should be noted

that in all treatments the DT50 values have been extrapolated more than twice

the study period and should be interpreted with care.

Conclusion Estimated soil photolysis DT50 values for BAS 750 F are 93 and 170 days for

the chlorophenyl- and triazole-labels, respectively. As such, a photolysis in soil

is expected to be of limited influence on degradation behaviour and metabolite

formation in soil.

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Biological degradation – biodegradation in soil

Table 64: Terrestrial field dissipation: other formulation (key study)

Study type Terrestrial field dissipation

Flag Key study

Test Substance BAS 750 F (mefentrifluconazole) applied in formulation BAS 750 01 F (EC) or

BAS 750 UA F (SC)

Endpoint DisT50 (non-normalised)

Value Range from 101 to 292 days (New York site = 281 days; North Dakota site =

286 days; Washington site = 286 days; California site = 266 days; Oklahoma

site = 292 days and Illinois site = 101 days)

[Note: DisT50field values were expressed as active ingredient

(mefentrifluconazole) but applied as formulation BAS 750 01 F (EC),

containing a nominal concentration of 100 g ai/L or BAS 750 UA F (SC),

containing a nominal concentration of 400 g ai/L. The target application rate

was 150 g ai/ha]

Reference (3.6.11) Jacobson et al. (2016a). Terrestrial field dissipation of the fungicide BAS 750 F

following broadcast applications of BAS 750 01 F (EC) or BAS 750 UA F (SC).

BASF Study Identification Number: 433578. BASF Registration Document

Number (Doc ID): 2015/7006396.



by the EPA Staff.

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Comments It should be noted that neither of the formulations tested are Revystar®

Fungicide, which may limit applicability of results. The application rate of the

active ingredient BAS 750 F is the maximum rate that will be applied as

Revystar® Fungicide however (150 g ai/ha, with the exception of the

Oklahoma soil where the target rate was 200 g ai/ha). Three applications were

made at each site (with the exception of the Illinois site where two applications

were made), which is also more than listed on the GAP and is therefore

considered a conservative estimate of the DT50 values.

The dissipation of BAS 750 F in soil under field conditions was investigated at

six sites in the U.S. As sampling and analysis are still ongoing, interim results

were reported. Based upon climatic information and characteristics of the soil

presented it is considered that the conditions in the study at US test sites can

be deemed comparable to those in the EU agricultural conditions to enable

them to be considered in support of the proposed EU use of BAS 750F, once

the final report is made available. Whether the conditions at the US test sites

are comparable to NZ conditions is unclear however.

BAS 750 F dissipated slowly with preliminary DisT50 values from 101 to 292

days. The 101 day result is unusually short as compared to the other 5 sites

with preliminary DT50 values ranging from 266-292 days.

The interim data presented are acceptable as presented thus far to give an

indication of the likely rate of dissipation of BAS 750 F in field conditions and

further supports the EU data in the consideration of the lack of significance of

the M750F003 metabolite in field conditions at the proposed GAP of 2 x 150 g

ai/ha. However, it should be noted that if interpretation of metabolite data and

the calculation of any kinetic parameters is required for M750F003 this could

prove difficult due to the multiple applications used within the field trials. Due

to the interim nature of the data study and areas that require clarification and

further investigation no further consideration of these data has been made in

this evaluation.

Conclusion The U.S. field DisT50 values (non-normalised) ranged from 101-292 days.

The metabolites 1,2,4-triazole and M750F003 were detected at all trial sites.

1,2,4-triazole was observed in some sites prior to or at application and at NY

(R140591), ND (R140592) these initial values were at quantifiable levels. The

metabolite M750F003 was detected at quantifiable amounts (>0.002 mg/kg) at

four of the six trial sites.

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Table 65: Terrestrial field dissipation: other formulation (key study)

Study type Terrestrial field dissipation study

Flag Key study

Test Substance BAS 750 F (mefentrifluconazole) applied in formulation EXP 5834378 F-AV

Endpoint DegT50

Value NA (see comments)

Reference (3.6.9) Schäufele (2015d). Field soil dissipation study of Reg. No. 5834378 in the

formulation EXP 5834278 F-AV on bare soil at six sites in Europe, 2013.

BASF Study Identification Number: 430699. BASF Registration Document

Number (Doc ID): 2015/1046920.



by the EPA Staff.

Comments Quantifiable residues of BAS 750 F residues were detected only in the first 20

cm of the soils. No residues above the LOQ were detected below 20 cm in any

sample at any site. Altogether, it can be concluded that BAS 750 F does not

show any significant tendency to move into deeper soil layers indicating low

potential to leach to groundwater.

See also final report amendment (Schäufele, 2015e) and EC DAR (EC 2017)

Doc ID 2015/1249176.

Conclusion NA (see kinetic evaluation in EC DAR (EC 2017) Doc ID 2015/1249176 for

DT50 endpoints)

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Table 66: Terrestrial field dissipation: other formulation (supporting study)

Study type Amendment to terrestrial field dissipation

Flag Supporting study

Test Substance BAS 750 F (mefentrifluconazole) applied in formulation EXP 5834378 F-AV

Endpoint NA (see comments)


Reference (3.6.10) Schäufele (2015e). Final report amendment No. 1: Field soil dissipation study

of Reg. No. 5834378 in the formulation EXP 5834278 F-AV on bare soil at six

sites in Europe, 2013. BASF Study Identification Number: 430699. BASF

Registration Document Number (Doc ID): 2015/1242234.



by the EPA Staff.

Comments Initial report (Schäufele (2015d) reported the sum of daily solar radiation but

the mean of daily solar radiation should have been reported instead. This

amendment does not impact the integrity of the study.

Conclusion NA (see comments)

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Table 67: Accumulation behaviour in soil under field conditions: other formulation (key study)

Study type Accumulation behaviour in soil under field conditions following repeated

application onto winter wheat over several years

Flag Key study

Test Substance BAS 750 F (mefentrifluconazole) applied in formulation BAS 750 01 F



Reference (3.6.18) Schäufele (2015b). Accumulation behaviour of BAS 750 F in soil under field

conditions in the United Kingdom following repeated application onto winter

wheat over several years. BASF Study Identification Number: 433573. BASF




by the EPA Staff.

Comments The study is ongoing; no residue data is presented within the interim report.

While this interim reports presents the study design no assessment of the

accumulation of BAS 750 F can be made.

Note that the test item applied in this study was not Revystar Fungicide but

formulation BAS 750 01 F. Whilst this also an emulsifiable concentrate

formulation containing the same concentration of mefentrifluconazole as

Revystar Fungicide (100 g/L), formulation BAS 750 01 F does not contain

fluxapyroxad.


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Table 68: Accumulation behaviour in soil under field conditions: other formulation (key study)

Study type Accumulation behaviour in soil under field conditions following repeated

application onto winter barley over several years

Flag Key study

Test Substance BAS 750 F (mefentrifluconazole) applied in formulation BAS 750 01 F



Reference (3.6.19) Schäufele (2015c). Accumulation behaviour of BAS 750 F in soil under field

conditions in Germany following repeated application onto winter barley over

several years. BASF Study Identification Number: 711494. BASF Registration

Document Number (Doc ID): 2015/1076326.



by the EPA Staff.

Comments The study is ongoing; no residue data is presented within the interim report.

While this interim reports presents the study design no assessment of the

accumulation of BAS 750 F can be made.

Note that the test item applied in this study was not Revystar Fungicide but




fluxapyroxad.


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Mobility in soil

Table 69: Adsorption/desorption in soil: active ingredient (key study)

Study type Soil adsorption/desorption

Flag Key study


Endpoint Kd/Koc

Value Kd values range from 29.75 to 121.5 mL/g

Koc values ranged from 2511 to 4958 mL/g

Lowest Kd from non-sand soil = 30.63 mL/g (La Gironda soil)

Lowest Koc from non-sand soil = 2511 mL/g (La Gironda soil)

[Note: Kd/Koc values were calculated from raw data presented in the study

report for use in EPA’s risk assessment as Freundlich sorption parameters

reported only]

Reference (3.6.21) Sacchi (2016). Adsorption / desorption behaviour of 14C-BAS 750 F on

different US, Japanese and European soil. BASF Study Identification Number:

433570. BASF Registration Document Number (Doc ID): 2016/3003661.


– Annex B.8 (AS) Environmental fate and behaviour (2017) is fully accepted by

the EPA Staff.

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Comments The following Kd and Koc values were measured for the test item in each soil:

Soil Soil Type Kd (mL/g) Koc (mL/g)

IN Loam 60.15 4930

New Jersey Loam 42.25 4225

Obhiro Loam 121.5 3575

Fiorentiono Poggio

Renactico 1 Loam 44.05 4405

La Gironda Sandy clay

loam 30.631 25111

Li10 Loamy sand 34.48 3629

Lufa 5M Sandy loam 36.18 3289

Lufa 2.12 Sand 29.75 4958

1 Values in bold are lowest values from a non-sand soil

2 Results for Lufa 2.1 soil not considered as soil type classified as a sand and

the EPA uses the lowest value, non-sand soil for the risk assessment

It should be noted that the adsorption/desorption results presented in the study

report were expressed as the Freundlich sorption parameters Kf, Kfoc and 1/n.

For use in the risk assessment the EPA has calculated the sorption

parameters Kd and Koc from the raw data included in the study report.

Conclusion For BAS 750 F the Kd values ranged from 29.75 to 121.5 mL/g and Koc

values ranged from 2511 to 4958 mL/g. According to the McCall scale (McCall

et al. 1981) of pesticide mobility, BAS 750 F would be classified as slightly

mobile.

The EPA uses the lowest value non-sand soil in the risk assessment, as such

the lowest Kd and Koc values were obtained for the La Gironda soil, with

values of 30.63 mL/g and 2511 mL/g, respectively.

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Bioconcentration/bioaccumulation studies

Table 70: Bioconcentration study: active ingredient (key study)

Study type Bioconcentration, flow-through, uptake period of 14 days

Flag Key study


Endpoint BCFKLg (whole fish)

Value 385

Reference (3.6.32) 14C-BAS 750 F (label: triazole-3(5)-C14):

Bioconcentration Study in the Rainbow Trout (Oncorhynchus mykiss).


– Annex B.9 (AS) Ecotoxicology (2017) is fully accepted by the EPA Staff.

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Comments It is noted in the DAR that the usual uptake phase for this test has a duration

of 28 days instead of 14 days in this study.

The steady state was reached before 3 days and thus there was sufficient

time to ensure the steady state was reached. The depuration phase was 7

days, 7 days only 3% of the accumulated active remained. Therefore the

reduced duration of the experiment is not expected to have adversely affected

the results. While only one test concentration has been studied, this is

acceptable according to OECD 305 (2012) this is under the proviso that a

justification has been submitted by the applicant. The justification submitted by

the applicant is presented below:

“The OECD guideline 305 on “Bioaccumulation in Fish” (adopted 2012) states

that “the testing of only one test concentration can be considered sufficient,

when it is likely that the bioconcentration factor (BCF) is independent of the

test concentration”. The guidance further mentions that for non-polar organic

substances the exposure of fish to a single concentration is expected to be

sufficient as no concentration effects are expected.

An extensive data review of Creton et al. (2013) supports the use of only one

test concentration in BCF studies specifically for plant protection products. The

researchers reviewed 55 active substances with a wide log KOW range (-0.81

to 6.9) and various modes of action. They compared BCF values from low and

high test concentrations (generally a factor of 10 apart) and found a linear

relationship for all examined dimensions (whole body, edible and non-edible

tissue). Among the 55 reviewed active substances also triazoles were present,

e.g. prothioconazole, triticonazole, metconazole and epoxiconazole. The ratio

between the ‘low-concentration BCF’ and ‘high-concentration BCF’ for

triazoles differed only between 0.85 and 1.19. Paragraph 78 from the OECD

305 guidelines defines that a concentration dependence is not indicated if

uptake and depuration rate (and therefore also the kinetic BCF as a function of

these rate constants) vary by less than 20% from two test concentrations. This

is the case for plant protection products and specifically for triazole fungicides.

The review by Creton et al. (2013) demonstrates clearly that no significant

difference between the BCF in low and high concentrations can be found for

plant protection products, although the data set considered substances with

highly differing physico-chemical properties and even different fish species in

the tests.

In order to minimize vertebrate testing and since no concentration effect is

expected for the triazole fungicide BAS 750 F, only one test concentration was

chosen to be sufficient for the respective bioconcentration study in fish.”

References:

OECD (2012): Test No. 305: Bioaccumulation in Fish: Aqueous and Dietary

Exposure, OECD Guidelines for the Testing of Chemicals, Section 2, OECD

Publishing

Creton S., Weltje L., Hobson H., Wheeler J.R. (2013): Reducing the number of

fish in bioconcentration studies for plant protection products by reducing the

number of test concentrations. Chemosphere 90 (2013), 1300–1304.

The Creton et al. (2013) paper demonstrated that there were no statistically

significant differences between BCF values determined using high or low test

concentrations. The RMS has noted that only some of the triazole data

presented in the paper has been included in the above consideration by the

Applicant. Additional triazole data for tetraconaole and tebuconzole is present

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– these indicate ratios of 1.04 and 1.69, respectively. It is noted that the ratio

for tebuconazole is the second highest ratio reported for all active substances

included in the study – and appears to be somewhat higher than that reported

for the other 5 triazole fungicides (prothioconazole, triticonazole, metconazole,

tetraconazole and epoxiconazole). Therefore, the range in values for triazole

fungicides (0.85-1.69) is somewhat wider than stated above. The maximum

difference observed for all pesticides is 2.4m this relatively high value is

observed for a substance with a very low BCF and differences might be due to

small experimental errors.

Given that is unknown whether a high or low concentration was tested for BAS

750 F – the range in ratios indicates that the BCF value could potentially be

15% lower or 70% higher if a further concentration had been tested. It is noted

that the whole fish BCFKLg value for BAS 750 F is 385. Therefore, assuming a

worst case ratio of 1.7 for triazoles – the BCF value would potentially increase

to 654.5. This value would be above the EPA’s bioaccumulation trigger value

of >500. As a consequence, it is considered possible that testing a further

concentration could have an impact on this evaluation.

In addition, it is noted that the Creton et al. (2013) study states that “data were

available from 166 studies of which 108 used only one test concentration”.

Therefore, the use of single test concentrations appears to be relatively

common.

In conclusion the presented BCFKLg should be considered with care

considering the potential for bioaccumulation.

Conclusion BCFKLg (whole fish) = 385 [Note this value should be treated with care given

the comments above]

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Ecotoxicity study summaries



metabolites were sourced from the mefentrifluconazole DAR unless otherwise stated. Study

summaries have only been included in Appendix J where there are comments in regard to individual

studies, and are provided in Table 71 to Table 109.

Aquatic ecotoxicity of the active ingredient

Short-term aquatic toxicity studies

Table 71: Acute toxicity to fish (rainbow trout): active ingredient (key study) [9.1]

Study type Acute toxicity to fish

Species Rainbow trout, Oncorhynchus mykiss

Flag Key study


Endpoint LC50 and NOEC

Value LC50 (96-hrs) = 0.532 mg/L (mean measured)

NOEC (96-hrs) = 0.142 mg/L

Reference (4.6.10) (2014a). BAS 750 F: Acute Toxicity Study in the Rainbow Trout

(Oncorhynchus mykiss).

Study Summary The summary in the Draft Assessment Report (DAR) – BAS 750F – Volume

3 – Annex B.9 (AS) Ecotoxicology (2017) is fully accepted by the EPA Staff.

Comments It was noted in the DAR that the body length of the test subjects was 5.5-6.6

cm, exceeding the recommended body length for this species (5.0 ± 1.0 cm).

This might have decreased the sensitivity of the test organisms. However, as

this was the only deviation, all the validity criteria were met and no adverse

effects were observed, the study is still considered acceptable.

Conclusion LC50 (96-hrs) = 0.532 mg/L (mean measured)

NOEC (96-hrs) = 0.142 mg/L

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Table 72: Acute toxicity to fish (zebrafish): active ingredient (key study) [9.1]


Species Zebrafish, Danio rerio

Flag Key study




NOEC for mortality (96-hrs) = 0.735 mg/L

Reference (4.6.13) (2015a). BAS 750 F (Reg. No. 5834378): Zebrafish Acute toxicity

test.



Comments It is noted in the DAR that the hardness and the conductivity exceeded the

recommended limit of 250 mg CaCO3/L and 10 μS cm-1 respectively,

although as all the validity criteria were met and no negative effects were

observed in the controls, this deviation is not expected to have adversely

affected the experiment.


NOEC for mortality (96-hrs) = 0.735 mg/L

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Table 73: Acute toxicity to Daphnia magna: active ingredient (key study) [9.1]

Study type Acute toxicity to aquatic invertebrates

Species Aquatic invertebrate, Daphnia magna

Flag Key study


Endpoint EC50 and NOEC

Value EC50 (48-hrs) = 0.944 mg/L (geometric mean measured)

NOEC (48-hrs) = 0.254 mg/L

Reference (4.6.23) Brzozowska (2014a). BAS 750 F: Daphnia magna, Acute Immobilisation

Test. BASF Study Identification Number: 433171. BASF Registration




Comments It was noted in the DAR that the temperature differed outside ±1°C (OECD

202 (2004)) and the hardness of the test medium is not reported. However as

all the validity criteria were met and no negative effects were observed in the

control organisms, these deviations are not expected to have adversely


Conclusion EC50 (48-hrs) = 0.944 mg/L (geometric mean measured)

NOEC (48-hrs) = 0.254 mg/L

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Table 74: Acute toxicity to saltwater mysid shrimp: active ingredient (key study) [9.1]


Species Mysid shrimp, Americamysis bahia

Flag Key study




NOEC (96-hrs) = 0.415 mg/L

Reference (4.6.29) VanHooser (2014a). BAS 750 F: Acute Toxicity Test With the Saltwater

Mysid, Americamysis bahia, Determined Under Flow-Through Test

Conditions. BASF Study Identification Number: 433266. BASF Registration




Comments It is noted in the study that a white precipitate was observed in some test

solutions, and consequently the results may underestimate the toxicity of the

active. Given that the sample solutions were centrifuged before analysis, it

can be expected that the mean measured samples are representative of the

dissolved concentrations the test organisms were exposed to, so no further

consideration is required.


NOEC (96-hrs) = 0.415 mg/L

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Table 75: Acute toxicity to algae: active ingredient (key study) [9.1]

Study type Acute toxicity growth inhibition test

Species Algae, Pseudokirchneriella subcapitata

Flag Key study


Endpoint ErC50 (72-hrs, geometric mean measured)

Value 1.352 mg/L

Reference (4.6.41) Brzozowska (2014b). BAS 750 F (Reg. No. 5834378) Pseudokirchneriella

subcapitata SAG 61.81 Growth Inhibition Test, Determined Under Flow-

Through Test Conditions. BASF Study Identification Number: 433170. BASF




Comments In the DAR it is noted that the temperature should be maintained within the

range of 21-24°C (OECD 201 (2011)) rather than 24.1-24.4°C. Given that the

deviation was only marginally above the limit, all the validity criteria were met

and no negative effects were observed in the controls, this deviation is not

expected to have adversely affected the study.

Conclusion ErC50 (72-hrs) = 1.352 mg/L (geometric mean measured)

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Species Marine diatom, Skeletonema costatum

Flag Key study


Endpoint IrC50 and NOEC

Value IrC50 (72-hrs) = 0.723 mg/L (initial measured concentration)

NOEC (72-hrs) = 0.111 mg/L (initial measured concentration)

IrC50 (96-hrs) = 0.704 mg/L (initial measured concentration)

NOEC (96-hrs) = 0.217 mg/L (initial measured concentration)

(in regard to endpoints see comments section below)

Reference (4.6.47) Bergfield (2015a). BAS 750 F: Growth Inhibition Test with the Marine Diatom,

Skeletonema costatum. BASF Study Identification Number: 433265. BASF




Comments It should be noted that these endpoints have been recalculated and this has

been summarised in the next table

During the test concentration did not remain stable (<80% of the initial

concentration), the mean of geometric mean concentration should have been

calculated.

Conclusion Not considered appropriate

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Study type Recalculation of endpoints from Bergfield (2015a) “BAS 750 F: Growth

Inhibition Test with the Marine Diatom, Skeletonema costatum” (as

summarised in the previous table)

Flag Key study


Endpoint ErC50

Value ErC50 (72-hrs) = 0.679 mg/L (geometric mean measured)

ErC50 (96-hrs) = 0.676 mg/L (geometric mean measured)

Reference (4.6.48) Horn (2016a). Recalculation of endpoints for the study by Bergfield A., 2015a

(BASF DocID 2015/7000620): “BAS 750 F: Growth Inhibition Test with the

Marine Diatom, Skeletonema costatum”. BASF Registration Document

Number (Doc ID): 2016/1292092.

Klimisch Score 1



Comments It is noted in the DAR that changes to the morphology of the cells should be

observed and some conditions of the test medium such as hardness and

conductivity were not reported.


ErC50 (96-hrs) = 0.676 mg/L (geometric mean measured)

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Species Freshwater diatom, Navicula pelliculosa

Flag Key study


Endpoint IrC50 and NOEC

Value IrC50 (72-hrs) = 1.57 mg/L

NOEC (72-hrs) = 0.358 mg/L

IrC50 (96-hrs) = 1.89 mg/L

NOEC (96-hrs) = 0.358 mg/L

(in regard to endpoints see also comments section below)

Reference (4.6.49) Bergfield (2015b). BAS 750 F: Growth Inhibition Test with the Freshwater

Diatom, Navicula pelliculosa. BASF Study Identification Number: 433178.

BASF Registration Document Number (Doc ID): 2015/7000618.



Comments It should be noted that these endpoints have been recalculated and this has

been summarised in the next table

Conclusion IrC50 (72-hrs) = 1.57 mg/L

NOEC (72-hrs) = 0.358 mg/L

IrC50 (96-hrs) = 1.89 mg/L

NOEC (96-hrs) = 0.358 mg/L

(in regard to endpoints see also comments section below)

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Study type Recalculation of endpoints from Bergfield (2015b) “BAS 750 F: Growth

Inhibition Test with the Freshwater Diatom, Navicula pelliculosa” (as

summarised in the previous table)

Flag Key study


Endpoint ErC50

Value ErC50 (72-hrs) = 1.347 mg/L (geometric mean measured)

ErC50 (96-hrs) = 1.577 mg/L

Reference (4.6.50) Horn (2016b). Recalculation of endpoints for the study by Bergfield A., 2015b

(BASF DocID 2015/7000618): “BAS 750 F: Growth Inhibition Test with the

Freshwater Diatom, Navicula pelliculosa”. BASF Registration Document

Number (Doc ID): 2016/1292093.





conductivity were not reported. Due to poor initial recovery and undissolved

test material in the solution, the nominal 7.0 mg ai/L treatment level was not

used for statistical analysis. However, basing the ECx values off the other

five test concentrations is acceptable.


ErC50 (96-hrs) = 1.577 mg/L

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Species Cyanobacterium, Anabaena flos-aquae

Flag Key study


Endpoint ErC50 and NOEC

Value ErC50 (72-hrs) = >3.08 mg/L (geometric mean measured)

NOEC (72-hrs) = 3.08 mg/L

ErC50 (96-hrs) = >3.08 mg/L (geometric mean measured)


Reference (4.6.51) Bergfield (2015c). BAS 750 F: Growth Inhibition Test with the

Cyanobacterium, Anabaena flos-aquae. BASF Study Identification Number:






conductivity were not reported.

Conclusion ErC50 (72-hrs) = >3.08 mg/L (geometric mean measured)


ErC50 (96-hrs) = >3.08 mg/L (geometric mean measured)


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Long-term aquatic toxicity studies

Table 81: Chronic toxicity to fish: active ingredient (key study)

Study type Early life-stage toxicity test


Flag Key study


Endpoint NOEC (36 days)

Value NOEC = 0.027 mg/L (mean measured), total length was most sensitive

toxicological endpoint

Reference (4.6.17)

2015a). BAS 750 F - Early Life-Stage Toxicity Test on the

Zebrafish (Danio rerio) in a flow through system.



Comments

It is noted in the DAR that the validity criterion of temperature difference

remaining within ±1.5°C was not met. However, the temperature minimum

was according to a continuous temperature measurement rather than

instantaneous which did not record any deviation. This would mean that the

marginal passing was temporary (45-hr) and probably did not affect the test.

This is supported by no negative effects being observed in the control

organisms. Additionally the analytical results pass outside ±20% of the

nominal, but the results were >100% of the nominal and the endpoint is

based on mean measured concentration and results are therefore corrected

for this deviation. Consequently, this failing of the validity criteria is not

expected to have adversely affected the test and is therefore considered

acceptable. The recommended duration of the test is 30 days post-hatch,

although the study duration of 32 days post-hatch is not expected to have

adversely affected the test.

Conclusion NOEC = 0.027 mg/L (mean measured), total length was most sensitive

toxicological endpoint

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Table 82: Chronic toxicity to fish: active ingredient (key study)

Study type Life cycle test


Flag Key study



Value 0.022 mg/L (mean measured)

Reference (4.6.67) ). BAS 750 F: Life Cycle Toxicity Test on the Zebrafish (Danio

rerio) in a Flow Through System.

Klimisch Score 1

Amendments/Deviations None

GLP Yes

Test Guideline/s OPPTS 850.1500 (Fish life cycle toxicity)

Nominal test

concentrations

0 (Control), 3.40, 6.40, 12.0, 23.0 and 44.0 μg/L

Mean-measured test

concentrations

F0 generation <LOD, 3.16 μg ai/L ±0.19 (93%); 6.95 μg ai/L ±0.43 (109%);

12.9 μg ai/L ±0.86 (107%); 22.2 μg ai/L ±2.92 (97%); 45.5 μg ai/L ±3.51

(104%)

F1 generation <LOD; 3.72 μg ai/L ±0.30 (109%); 7.36 μg ai/L ±0.36 (115%);

13.3 μg ai/L ±0.98 (111%); 24.5 μg ai/L ±1.31 (107%); 46.8 μg ai/L ±2.53

(106%) [μg ai/L ±SD (% of nominal)]

Analytical measurements Yes, LC-MS-MS

Validity criteria met Yes

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Study Summary A fish full life cycle test using zebrafish (Danio rerio) was conducted to

assess the effects of BAS 750 F on population-relevant endpoints over two

generations and to determine a no observed effect concentration (NOEC).

The exposure period was 140 days. The experiment was conducted under

flow-through conditions with continuous exposure to five concentrations of

the test substance and a dilution water control: 0 (Control), 3.40, 6.40, 12.0,

23.0 and 44.0 μg/L as nominal concentrations based on active ingredient.

To initiate the F0-generation exposure, freshly fertilized zebrafish eggs (<5

hours old) were obtained by proportionally pooling eight clutches obtained

from non-exposed brood stock fish. Each test group initially consisted of 150

embryos evenly and randomly distributed among five replicates. After

hatching the zebrafish were allowed to grow to maturity. Starting on test day

71 spawning trays were inserted once weekly in each replicate aquarium to

monitor the onset of sexual maturity by qualitatively estimating the egg

production. On test days 104-106, fish of the F0-generation test groups were

reduced to form spawning groups consisting of five males plus five females

per replicate. Starting on test day 107, egg production and fertility were

enumerated on 22 days. After the reproduction evaluation period, the F0

spawning groups were terminated on test day 140. Upon sacrifice the

phenotypic sex of each F0 generation individual was confirmed with a direct

macroscopic evaluation of the gonads.

Fertilized eggs from the F0-test groups were used to start a first filial

generation (F1-generation) on test day 98. The F1-generation test groups

consisted of 100 embryos from the corresponding F0-test group evenly

distributed among 4 replicates. The F1-generation fish were exposed for a

total of 36 days, equivalent to an early life stage test, at nominal

concentrations identical to the parental exposure. Over the two generations,

effects on hatching success, time to hatch, survival, growth (body length and

weight) and signs of toxicity (appearance/behaviour) were recorded.

Additionally the reproduction of the F0-generation was quantitatively

evaluated by assessing fecundity (eggs per female reproductive day) and

fertility.

Samples for concentration control analyses were collected generally weekly

from all test groups during the exposure period. The concentration of the test

substance in the control group was below the limit of quantification

throughout the exposure period. The mean measured concentrations were in

the range of 93-109% of the corresponding nominal concentrations in the F0-

generation and in the range of 106-115% of the corresponding nominal

concentration in the F1-generation. The individually measured concentrations

during the exposure period were generally within the range ±20% of the

nominal concentrations with very few exceptions.

All individually measured values were within a range of ± 20% of the mean

measured. Both, the nominal and mean measured concentrations are

considered an accurate representation of the actual exposure concentrations

over the course of the test.

Environmental and water quality parameters were monitored regularly

throughout the test and remained within acceptable ranges. Water

temperature measurements were generally within the range of 27±1.5°C. The

pH was stable during the whole exposure period and was in the range 7.8-

8.2. The dissolved oxygen concentrations were maintained between 5.9 and

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8.5 mg/L, corresponding to approximately 73–105% of the maximum air

saturation value at test temperature.

There was no adverse treatment-related effect on hatching success, time to

hatch, survival, or any apparent signs of toxicity and abnormalities in the F0-

generation fish. However among the F0-generation fish sacrificed at

reduction (test days 104-106) and at the termination of the spawning groups

(test day 140), the body weight and length of the female fish from treatment

group 5 (44.0 μg ai/L) were significantly reduced in comparison to the control

group (2-3% for body length and 12-13% for body weight compared to the

control group). The body weight and length of male fish on both occasions

was not affected in any of the treatment groups.

Moreover there was a statistically significant reduction in fecundity

(approximately 10% in comparison to the control group), but not fertility in F0-

generation fish of treatment group 5 (44.0 μg ai/L). This finding is consistent

with the reduced body weight of adult female fish in this treatment group. In

the F1-generation the survival from swim-up until termination was statistically

significantly reduced in comparison to the control group in test group 5 (44.0

μg ai/L). There was no adverse treatment related effect on hatching success,

time to hatch, or juvenile fish growth. Overall the pattern of effects are

consistent and indicate a systemic toxic effect observed only in the highest

treatment group.

In conclusion the overall NOEC identified in this test was 23.0 μg ai/L

(nominal concentration) 22.2 μg ai/L (mean measured concentration in the

F0-generation). The LOEC was 44.0 μg ai/L (nominal concentration) and 45.5

μg ai/L (mean measured concentration in the F0-generation).

Comments None

Conclusion NOEC (140-day) = 0.022 mg/L (mean measured)

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Table 83: Endocrine disruption in fish: active ingredient (key study)

Study type Fish sexual development test


Flag Key study


Endpoint NOEC (69 days, mean measured)

Value ≥0.045 mg ai/L

Reference (4.6.18) BAS 750 F Fish sexual development test on the zebrafish

(Danio rerio).



Comments It is noted in the DAR that the high percentage coefficients of variation for

male vitellogenin (VTG) measurements. This was caused by some males

having abnormally high VTG values. Although the reason is unknown,

contamination with female blood has been excluded by only using scalpels

once. High VTG individuals were found in the control and all treatment

groups independent of concentration. The RMS equally notes that the

percentage coefficients of variations were present in the females that also

appeared in the control and all treatment groups independent of

concentration. No significant differences in VTG concentrations were

observed between any concentration and the control for both male and

female fish, although no conclusions on endocrine disruption can be drawn

based upon this. While the high coefficient of variations may increase the

difficulty of detecting statistically significant differences, no clear dose

dependent effects on VTG appear to be present for either gender.

Conclusion NOEC (69 days) ≥0.045 mg ai/L (mean measured)

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Table 84: Chronic toxicity to Daphnia magna: active ingredient (key study)

Study type Chronic toxicity semi-static test


Flag Key study



Value 0.0091 mg/L (time-weighted mean)

Reference (4.6.31) Janson (2014a). Chronic toxicity of BAS 750 F (Reg.No.5834378) to Daphnia

magna Straus in a 21-day semi-static test. BASF Study Identification

Number: 433175. BASF Registration Document Number (Doc ID):

2014/1098028.



Comments It is noted in the DAR that any tests for significance between the control and

solvent control was not reported, although there does not appear to be any

discrepancies between the solvent control and the water control that would

be deemed significant and a pooled control was used for comparison with the

test concentrations. Therefore, this is considered not to impact the results.

Conclusion NOEC (21 days) = 0.0091 mg/L (time-weighted mean)

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Table 85: Chronic toxicity to Daphnia longispina: active ingredient (key study)

Study type Chronic toxicity (semi-static test) to Daphnia longispina

Species Daphnia longispina

Flag Key study


Endpoint NOEC (21 days, time-weighted mean)

Value 0.0342 mg/L

Reference (4.6.32) Janson (2015b). Chronic toxicity of BAS 750 F (Reg.No.5834378) to Daphnia

longispina in a 21-day semi-static test. BASF Study Identification Number:

733331_1. BASF Registration Document Number (Doc ID): 2015/1003912

and 2015/1251197(report amendment)



Comments It is noted in the DAR that any tests for significance between the controls was

not reported, although there does not appear to be any discrepancies

between the solvent control and the water control that would be deemed

significant. Therefore, this is considered not to impact the results.


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Table 86: Chronic toxicity to Daphnia pulex: active ingredient (key study)

Study type Chronic toxicity semi-static test

Species Daphnia pulex

Flag Key study


Endpoint NOEC (21 days, time-weighted mean)

Value 0.0276 mg/L

Reference (4.6.34) Janson (2015a). Chronic toxicity of BAS 750 F (Reg.No.5834378) to Daphnia

pulex in a 21-day semi-static test. BASF Study Identification Number:




Comments It is noted in the DAR that tests for significance between the controls was not

reported, although there does not appear to be any discrepancies between

the solvent control and the water control that would be deemed significant.

Therefore, this is considered not to impact the results.


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Acute/sub-chronic toxicity to sediment-dwelling organisms

Table 87: Acute and sub-chronic toxicity to sediment-dwelling organisms: active ingredient

(key study)

Study type Toxicity test under static-renewal conditions, spiked sediment

Species Midge, Chironomus dilutus

Flag Key study



Value NOEC (10 days) = 7.08 mg/kg dry sediment (midge growth, geometric mean

measured)

Reference (4.6.36) Clark (2015a). BAS 750 F – 10-day toxicity test exposing midge (Chironomus

dilutus) to a test substance applied to sediment under static-renewal

conditions. BASF Study Identification Number: 766634. BASF Registration




Comments The RMS notes that the test guidelines EPA 850.1735 (1996) is intended for

testing saltwater mysids rather than Chironomus species. Additionally,

dissolved oxygen levels nearly fell below (3.5 mg/L) the acceptable levels

according to EPA 850.1735, although increasing the flow rate appears to

have mediated this. The minimum light intensity was 280 lux rather than the

minimum of 500 lux recommended in EPA 850.1735 (1996), given there were

no observed adverse effects on the controls, this deviation is not expected to

have adversely affected the study. The EPA considers that the study is

robust and the information can be used for the assessment of the chemical.

It is noted in the DAR that arithmetic mean measured concentrations rather

than geometric mean measured concentrations have been used to calculate

the endpoints, resulting in the endpoints slightly underestimating toxicity.

Consequently the endpoints have been recalculated using geometric mean

measured concentration so that the EC50 is >96 mg ai/kg dry sediment, the

NOEC for midge survival is 22 mg ai/kg dry sediment and the NOEC for

midge growth is 7.08 mg ai/kg dry sediment. The study is considered

acceptable and suitable for risk assessment purposes and the proposed

endpoint is an EC50 of >96 mg ai/L and a NOEC of 7.08 mg ai/L.

Conclusion NOEC (10 days) = 7.08 mg/kg dry sediment (midge growth, geometric mean

measured)

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(key study)

Study type Acute and sub-chronic toxicity test under static-renewal conditions, spiked

sediment

Species Freshwater amphipod, Hyalella azteca

Flag Key study


Endpoint NOEC (10 days, mean measured)

Value NOEC (10 days) = 100 mg/kg dry sediment (amphipod growth)

Reference (4.6.39) Clark (2015b). BAS 750 F – 10-day toxicity test exposing freshwater

amphipods (Hyalella azteca) to a test substance applied to sediment under

static-renewal conditions. BASF Study Identification Number: 733145. BASF




Comments It is noted in the DAR that the conditions of the overlying water varied and

were not equal to the ranges expected for reconstituted water. In particular,

conductivity was 380-480 μS/cm although it should range over 330-360

μS/cm according to 850.1735. Given that no negative effects were observed

in the controls, the overlying water is not expected to have adversely affected

the test. Additionally, the length of the test organisms should be measured

and considered with growth, there is no indication effects to length in the

report, although as there has been no effect on weight, it is not expected that

length would have been significantly affected.

Conclusion NOEC (10 days) = 100 mg/kg dry sediment (amphipod growth)

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(key study)

Study type Acute and sub-chronic toxicity test under static-renewal conditions, spiked

sediment

Species Estuarine amphipod, Leptocheirus plumulosus

Flag Key study


Endpoint NOEC and LC50 (10 days, mean measured)

Value NOEC (10 days) = 95 mg/kg dry sediment (amphipod survival)

LC50 (10 days) > 95 mg/kg dry sediment

Reference (4.6.40) Clark (2015c). BAS 750 F – 10-day toxicity test exposing estuarine

amphipods (Leptocheirus plumulosus) to a test substance applied to

sediment under static conditions. BASF Study Identification Number: 433271.

BASF Registration Document Number (Doc ID): 2015/7000623.



Comments It’s noted in the DAR that 800 mL of overlying water (EPA 850.1740(1996))

should be used rather than 725 mL, given all the validity criteria were met

and no negative effects were observed in the controls, this deviation is not

expected to have adversely affected the study.

Conclusion NOEC (10 days) = 95 mg/kg dry sediment (amphipod survival mean

measured)

LC50 (10 days) > 95 mg/kg dry sediment (mean measured)

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Chronic toxicity to sediment-dwelling organisms

Table 90: Chronic toxicity to sediment-dwelling organisms: active ingredient (key study)

Study type Chronic toxicity test, static, spiked sediment

Species Midge, Chironomus riparius

Flag Key study


Endpoint NOEC (28 days, initial measured based on emergence rate and development

rate)

Value ≥1.158 mg/kg dry sediment (emergence rate and development rate, based on

initial measured concentrations)

Reference (4.6.38) Backfisch and Weltje (2015a). Chronic toxicity of Reg. No. 5834378 to the

non-biting midge Chironomus riparius. BASF Study Identification Number:




Comments It is noted in the DAR that egg masses should be collected four or five days

before test initiation according to OECD 218 (2004) rather than three days

prior in this study, although no adverse effects were observed in the control,

so this deviation is not expected to have adversely affected the study.

Conclusion NOEC (28 days) ≥1.158 mg/kg dry sediment (emergence rate and

development rate, based on initial measured concentrations)

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Aquatic ecotoxicity of metabolites of mefentrifluconazole

Table 91: Chronic toxicity to fish: metabolite M750F001, 1,2,4-triazole (key study)

Study type Early life-stage toxicity test


Flag Key study

Test Substance Metabolite M750F001 (1,2,4-triazole)

Endpoint NOEC

Value 3.20 mg/L (nominal)

Reference (4.6.73) 2002). 1,2,4-triazole – juvenile growth test, fish

(Onchorhynchus mykiss).

Study Summary The summary in the Draft Assessment Report (DAR) – Epoxiconazole –

Volume 3, Annex B, B.9, Ecotoxicology (2006) is fully accepted by the EPA

Staff.

Comments Note that the NOErC endpoint determined in the study was ≥100 mg test

item/L. Since 3.20 mg/L was the endpoint selected in the DAR (2006), the

EPA aligned with this decision.

Conclusion NOEC = 3.20 mg/L (nominal)

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Table 92: Acute toxicity to algae: metabolite M750F005 (key study)



Flag Key study

Test Substance Metabolite M750F005

Endpoint ErC50 (72-hrs)

Value ≥8.572 mg/L (geometric mean)

Reference (4.6.45) Rzodeczko (2016b). Reg. No. 6003433 (metabolite of BAS 750 F,

M750F005) Pseudokirchneriella subcapitata SAG 61.81 Growth Inhibition





Comments It is noted in the DAR that the pH should increase by no more than 1.5 over

the course of the test, and the pH increased from 7.24-8.82 in the solvent

control, and from 7.06-8.62 in the 4-fold dilution. This is only marginally over

the 1.5. This deviation is not expected to have adversely affected the

experiment.

Conclusion ErC50 (72-hrs) ≥8.572 mg/L (geometric mean)

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Table 93: Acute toxicity to fish: metabolite M750F006 (key study)



Flag Key study


Endpoint LC50 (96-hrs)

Value 6.20 mg/L (geometric mean)

Reference (4.6.12) (2016c). Reg. No. 5863469 (Metabolite of BAS 750 F,

M750F006) Rainbow trout, Acute toxicity test.



Comments It is noted in the DAR that given that signs of treatment related intoxication

were observed at 2.696 mg/L the LOEC and NOEC should be 2.696 and

1.478 mg/L respectively. It is also noted that the conductivity of 580-590

μS/cm exceeds the recommended conductivity of ≤10 μS/cm in OECD 203

(1992). Given all the validity criteria were met and no adverse effects were

observed in the controls, this deviation is not expected to have negatively


Conclusion LC50 (96-hrs) = 6.20 mg/L (geometric mean)

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Table 94: Acute toxicity to Daphnia magna: metabolite M750F006 (key study)



Flag Key study


Endpoint EC50 (48-hrs)

Value 4.42 mg/L (48-hrs) geometric mean

Reference (4.6.26) Rzodeczko (2015c). Reg. No. 5863469 (Metabolite of BAS 750 F,

M750F006) Daphnia magna, Acute immobilisation test. BASF Study

Identification Number: 433190. BASF Registration Document Number (Doc

ID): 2015/1001492.



Comments It is noted in the DAR that there were mortalities observed in line with the

probit curve at 0.84 and 1.83 mg/L, even though they were not significant,

treatment related mortality appears to be present at these test

concentrations. Therefore the NOEC has been adjusted to reflect this.

Conclusion EC50 = 4.42 mg/L (48-hours geometric mean)

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Table 95: Acute toxicity to algae: metabolite M750F006 (key study)



Flag Key study


Endpoint ErC50 (72-hrs)

Value 1.424 mg/L (geometric mean)

Reference (4.6.44) Rzodeczko (2016c). Reg. No. 5863469 (Metabolite of BAS 750 F,

M750F006) Pseudokirchneriella subcapitata SAG 61.81 Growth Inhibition





Comments It is noted in the DAR that the pH should increase by no more than 1.5 over

the course of the test, and the pH increased from 7.24-8.82 in the solvent

control. As this only occurred in the solvent control, all the validity criteria

were met and no negative effects were observed in the controls, this

deviation is not expected to have adversely affected the experiment.

Conclusion ErC50 (72-hrs) = 1.424 mg/L (geometric mean)

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Table 96: Acute toxicity to Daphnia magna: metabolite M750F007 (key study)



Flag Key study


Endpoint EC50 (48-hrs)

Value >10 mg/L (analytically confirmed nominal)

Reference (4.6.24) Backfisch and Härthe (2015a). Acute toxicity of Reg. No. 6003432

(M750F007; metabolite of BAS 750 F) to Daphnia magna Straus in a 48 hour

static test. BASF Study Identification Number: 433184. BASF Registration




Comments It is noted in the DAR that the although mean measured concentrations were

not maintained within ±20% of the nominal, for 10 mg/L the recovery was

100% at initiation and 98.2% at 48h. As the endpoints are >10 mg/L, basing

the endpoint off nominal concentrations is acceptable.

Conclusion EC50 (48-hrs) >10 mg/L (analytically confirmed nominal)

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Soil toxicity of the active ingredient

Toxicity to terrestrial plants

Table 97: Effects on non-target plants (seedling emergence): formulation BAS 750 01 F

(supporting study)

Study type Effects on non-target plants (seedling emergence)

Species Ten species: oilseed rape (Brassica napus), lettuce (Lactuca sativa), tomato

(Solanum lycopersicum), green cabbage (Brassica oleracea var. sabellica),

soya bean (Glycine max), carrot (Daucus carota), onion (Allium cepa), rye

grass (Lolium multiflorum), wheat (Triticum aestivum) and corn (Zea mays).

Flag Supporting study (see comments)

Test Substance BAS 750 01 F (emulsifiable concentrate formulation containing 100 g/L

mefentrifluconazole)

Endpoint NOER, ER25 and ER50 (21 days, seedling emergence)

Value NOER (21 days, plant dry weight) = 750 g Tl/ha [equivalent to 75 g ai/ha

based on a mefentrifluconazole concentration of 100 g/L]

ER25 (21 days, seedling emergence) >1500 mL TI/ha [equivalent to >150 g

ai/ha based on a mefentrifluconazole concentration of 100 g/L]



All species showed equal sensitivity to the test item.

Reference (4.6.70) Marquardt (2015a). BAS 750 01 F: A test to determine the effects on non-

target plants. BASF Study Identification Number: 730827. BASF Registration



3 – Annex B.9 (PPP) Ecotoxicology (2017) is fully accepted by the EPA Staff.

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Comments Note that the test item applied in this study was not Revystar Fungicide but




fluxapyroxad however.

The following comments were noted in the DAR:

Pre-emergence application of BAS 750 01 F under worst-case greenhouse

conditions did not result in treatment-related symptoms of phytotoxicity for

any of the tested plant species. No adverse effects on seedling emergence

and plant height were observed for all plant species tested up to and

including 1500.0 mL BAS 750 01 F/ha. Statistically significant effects on dry

weight were observed for wheat at an application rate of 1500.0 mL BAS 750

01 F/ha.

The ER50 value based on seedling emergence, plant height and dry weight

was >1500.0 mL BAS 750 01 F/ha for all tested plant species (the highest

rate tested). The NOER for phytotoxicity, seedling emergence and plant

height was ≥1500.0 mL BAS 750 01 F/ha, and the NOER for plant dry weight

was 750.0 mL BAS 750 01 F/ha.

The study was carried out according to GLP and follows the guideline OECD

208 with no significant deviations. The study report notes that there were a

number of deviations from guidance with regards to relative humidity, with

levels less than the recommended minimum of 45% (mean minimum 40% for

seven days after application for onion, mean minimum 40.34% for two days

for all other species). This is not considered to have had a significant effect

on the results as the study validity criteria were met.

The apparent large deviations from the control that do not result in

statistically significant results indicate that the study design lacks sensitivity.

However as no effects greater than 50% were observed, and as there

appears to be no dose-response relationship for any of the tested species,

the ER50 value derived from this study is considered appropriate for risk

assessment. That said there is uncertainty regarding the NOER values

derived.

Conclusion NOER (21 days, plant dry weight) = 750 g Tl/ha [equivalent to 75 g ai/ha






All species showed equal sensitivity to the test item.

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Table 98: Effects on non-target plants (vegetative vigour): formulation BAS 750 01 F

(supporting study)

Study type Effects on non-target plants (vegetative vigour)

Species Ten species: oilseed rape (Brassica napus), lettuce (Lactuca sativa), tomato

(Solanum lycopersicum), green cabbage (Brassica oleracea var. sabellica),

soya bean (Glycine max), carrot (Daucus carota), onion (Allium cepa), rye

grass (Lolium multiflorum), wheat (Triticum aestivum) and corn (Zea mays).


Test Substance BAS 750 01 F (emulsifiable concentrate formulation containing 100 g/L

mefentrifluconazole)

Endpoint NOER, ER25 and ER50 (21 days, plant dry weight)

Value NOER (21 days, plant dry weight) = 1500 mL TI/ha [equivalent to 150 g ai/ha


ER25 (21 days, plant dry weight) >1500 mL TI/ha [equivalent to >150 g ai/ha




All species showed equal sensitivity.

Reference (4.6.71) Marquardt (2015a). BAS 750 01 F: A test to determine the effects on non-

target plants. BASF Study Identification Number: 730828. BASF Registration

Document Number (Doc ID): 2016/7010990



Comments Note that the test item applied in this study was not Revystar Fungicide but




fluxapyroxad however.

The following comments were noted in the DAR:

Post-emergence application of BAS 750 01 F under worst-case greenhouse

conditions resulted in no treatment-related symptoms of phytotoxicity for all

tested plant species. Thus, the NOER was ≥1500.0 mL BAS 750 01 F/ha for

all tested plant species.

The ER50 value based on plant dry weight and height was >1500.0 mL BAS

750 01 F/ha for all tested plant species (the highest rate tested).

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227 with no significant deviations. The apparent large deviations from the

control that do not result in statistically significant results indicate that the

study design lacks sensitivity. However as no effects greater than 25% were

observed, this is not thought to have had an adverse impact on the study. As

there appears to be no dose-response relationship for any of the tested

species, the ER50 value derived from this study is considered appropriate for

risk assessment.

Conclusion NOER (21 days, plant dry weight) = 1500 mL TI/ha [equivalent to 150 g ai/ha






All species showed equal sensitivity.

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DECEMBER 2019

Terrestrial vertebrate toxicity of the active ingredient

Acute toxicity to birds (oral)

Table 99: Acute toxicity to birds (oral): active ingredient (key study) [9.3]

Study type Acute toxicity to birds (single dose)

Species Bobwhite quail, Colinus virginianus

Flag Key study


Endpoint LD50 and NOEL (acute oral)

Value LD50 = 816 mg ai/kg bw

NOEL = 300 mg/kg bw

Reference (4.6.2) (2014a). BAS 750 F - Acute toxicity in the bobwhite quail (Colinus

virginianus) after single administration (LD50).



Comments The following comments were included in the DAR:

The study is considered acceptable and suitable for risk assessment

purposes. The RMS agrees that the test conditions being outside the

guideline levels did not have a negative impact on the test.

Conclusion LD50 (acute oral) = 816 mg ai/kg bw

NOEL (acute oral) = 300 mg/kg bw

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Species Mallard duck, Anas platyrhychos

Flag Key study


Endpoint LD50 and NOEL (acute oral)

Value LD50 >2000 mg/kg bw

[Note that based on the EFSA guidance in cases where there is no mortality

the LD50 can be extrapolated using a factor of 1.614 (5 birds tested at limit

dose) by multiplying the limit dose by the extrapolation factor (ie. 2000 x

1.614 = 3228 mg ai/kg]

NOEL (mortality) = >2000 mg/kg bw

Reference (4.6.3) 2014b). BAS 750 F - Acute toxicity in the mallard duck (Anas

platyrhynchos) after single oral administration (LD50).

.





purposes. The RMS agrees that the environmental test conditions being

outside the guideline levels did not have a negative impact on the test, and

that the temperature exceeded self-imposed rather than the guideline limits,

whereas maximum humidity of 100% exceeded the guideline maximum of

70%. Additionally it is noted that the variation in the test organisms’ body

weight of 16.8% exceeds the recommended ±10% in EPA 850.2100 (1996),

although as no negative effects were observed in the controls and consistent

responses were observed across test organisms, this deviation is not

considered to have adversely affected the test.

Conclusion LD50 (acute oral) >2000 mg/kg bw

[Note that based on the EFSA guidance in cases where there is no mortality

the LD50 can be extrapolated using a factor of 1.614 (5 birds tested at limit

dose) by multiplying the limit dose by the extrapolation factor (ie. 2000 x

1.614 = 3228 mg ai/kg]

NOEL (mortality) = >2000 mg/kg bw

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Species Canary, Serinus canaria

Flag Key study


Endpoint LD50 (acute oral)

Value LD50 (acute oral) >2860 mg ai/kg bw

[Note that based on the EFSA guidance in cases where there is a single

mortality the LD50 can be extrapolated using a factor of 1.228 (5 birds tested

at limit dose) by multiplying the limit dose by the extrapolation factor (ie. 2860

x 1.228 = 3512 mg ai/kg]

Reference (4.6.4) (2015a). BAS 750 F - Acute toxicity in the canary (Serinus canaria)

after single oral administration (LD50).





purposes and the proposed endpoints are an LD50 of >2860 mg ai/kg bw and

a NOEL for mortality of ≥2860 mg ai/kg bw. The RMS agrees that humidity

exceeding the guideline levels did not have a negative impact on the test,

and that the temperature passed outside self-imposed rather than guideline

limits. It is additionally noted that food should be withheld for a minimum of

15-hrs (EPA 850.2100 (1996) prior to dosing rather than 2-3 hrs, and the

variation in body weight was 12.3%, only marginally exceeding the

recommended maximum of 10%. Given that the capsules were ingested and

no regurgitation was observed, these deviations are not expected to have

adversely affected the experiment.

Conclusion LD50 (acute oral) = >2860 mg/kg bw

[Note that based on the EFSA guidance in cases where there is a single

mortality the LD50 can be extrapolated using a factor of 1.228 (5 birds tested

at limit dose) by multiplying the limit dose by the extrapolation factor (ie. 2860

x 1.228 = 3512 mg ai/kg]

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Acute toxicity to birds (dietary)

Table 102: Acute toxicity to birds (dietary): active ingredient (disregarded study)

Study type Acute toxicity to birds (dietary)


Flag Disregarded (see comments)


Endpoint Study deemed unreliable

Value 858 mg/kg bw/d

Reference (4.6.5) (2014c). BAS 750 F - Avian dietary toxicity test in chicks of the bobwhite

quail (Colinus virginianus).



Comments In the DAR it is stated that food avoidance and the toxic effect of the item has

impacted food consumption and body weight data. Consequently, higher

concentration dose groups resulted in reduced daily doses. Therefore,

despite some clear effects on mortality, the effects cannot be separated from

the issue of food avoidance meaning doses cannot reliably attributed to

effects. Additionally, the effect of food avoidance may be causing starvation

and contributing to the mortalities. These issues will result in endpoints that

underestimate the toxicity to birds.

Note this study was also amended by Keller (2015a, BASF Registration

Document Number (Doc ID): 215/1223324), but does not affect the endpoint.

Conclusion Study deemed unreliable

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Table 103: Acute toxicity to birds (dietary): active ingredient (disregarded study)

Study type Acute toxicity to birds (dietary)


Flag Disregarded study


Endpoint LD50 (8-day dietary)

Value Study deemed unreliable

Reference (4.6.7) (2014d). BAS 750 F - Avian dietary toxicity test in ducklings of the

mallard duck (Anas platyrhynchos).



Comments It is concluded in the DAR that under the conditions of this study, the LD50 for

mallard ducklings (Anas platyrhynchos) was 8347 mg ai/kg diet (extrapolated

value). The LD50 exceeded the highest tested dietary concentration group of

7500 mg ai/kg diet. Calculated on the basis of daily doses, the LD50 was

1213 mg ai/kg bw/day. The "No Observed Effect Level" (NOEL) was <1480

mg ai/kg diet. The NOEL calculated on the basis of daily dose was <244 mg

ai/kg bw/day.

The RMS notes that food avoidance and the toxic effect of the item has

impacted food consumption and bodyweight data. Consequently, higher

concentration dose groups resulted in reduced daily doses. Therefore,

despite some clear effects on mortality, the effects cannot be separated from

the issue of food avoidance meaning doses cannot reliably be attributed to

effects of the active substance. Additionally, the effect of food avoidance may

be causing starvation and contributing to the mortalities. These issues will

result in endpoints that underestimate the toxicity to birds. The study has

proposed an extrapolated value for the LC50, however as there is no clear

dose-response relationship and the confidence limits for the value range over

a factor of 10, the proposed value cannot be accepted.

The RMS agrees that the temperature gradient should be between 22-38°C,

although the minimum temperature reached 17.1°C. Given the temperature

gradient with the ceramic heater and no negative effects observed in the

controls, the test conditions exceeding the recommended values are not

expected to have adversely affected the test. Additionally the mean body

weight for the 1480 mg ai/kg diet group had significantly reduced mean body

weight at day 0, which would make any significant decline in body weight for

this group over the course of the test more difficult to define from the initial

reduced weight.

Conclusion Study deemed unreliable

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Chronic toxicity to birds (reproduction)

Table 104: Chronic toxicity to birds (reproduction): active ingredient (key study)

Study type Chronic toxicity to birds (reproduction)


Flag Key study


Endpoint NOEC (22 weeks)

Value 285 mg ai/kg diet (25.3 mg ai/kg bw/day)

Reference (4.6.8) 2014a). BAS 750 F: A reproduction study with the Northern

bobwhite.



Comments In the DAR the following comments are noted:


purposes. The relative humidity of the adult study room and the brooding

pens were below the recommended levels of 45-70%. Ideally the water

should be changed every day rather than every 2-3 days as it is in a trough.

Given that all the validity criteria were met and no other negative effects were

observed in the controls, these deviations are not thought to have adversely

affected the experiment. Although there is an apparent dose-response in the

number of eggs laid per hen per day, this does not follow through to other

reproductive parameters such as hatchlings/hen. Therefore no changes to

the NOEC are proposed.

Conclusion NOEC (22 weeks) = 285 mg ai/kg diet (25.3 mg ai/kg bw/day)

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Table 105: Chronic toxicity to birds (reproduction): active ingredient (key study)

Study type Chronic toxicity to birds (reproduction)


Flag Key study


Endpoint NOEC (21 weeks)

Value 600 mg ai/kg diet (80.5 mg ai/kg bw/day)

Reference (4.6.9) 2015a). BAS 750 F: A reproduction study with the Northern

bobwhite.



Comments The following comments are stated in the DAR:


purposes and the proposed endpoints are a NOEC of 600 mg ai/kg diet (80.5

mg ai/kg bw/day). Although statistically significant in reduction in body mass

and gain of adult body weight was observed at 600ppm, this was not

considered test substance related as is due to the reduction in the body

weight of two female birds. Similar body reductions were not observed in the

15 surviving female birds at this concentration and in any of the surviving

male birds, and no dose response relationship was present for the other

concentration. Furthermore the range and standard deviations for these data

indicate both that the recorded weights were highly variable, and that these

two birds are considered to be outliers. Therefore the significant reduction is

not considered to be sufficient for reducing the NOEC to 300 mg ai/kg diet.

The environmental conditions in several areas exceeded the recommended

levels. The light intensity of the adult pens should be around 65 lux. Eggs

should be stored in a cold room of 13-16°C with a relative humidity of 55-

80%, and the relative humidity of the incubator should be around 70%. Given

that no negative effects were observed in the control, these deviations are

not expected to have had an adverse effect on the study.

Conclusion NOEC (21 weeks) = 600 mg ai/kg diet (80.5 mg ai/kg bw/day)

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Toxicity of the active ingredient to terrestrial invertebrates

Acute toxicity to pollinators

Table 106: Acute toxicity to honey bees: active ingredient (key study) [9.4]

Study type Acute toxicity to honey bees (oral and contact)

Species Honey bee, Apis mellifera L.

Flag Key study


Endpoint Acute oral and contact LD50 (48-hrs)

Value Acute oral LD50 (48-hrs) >100 µg ai/bee

Acute contact LD50 (48-hrs) >100 µg ai/bee

Reference (4.6.53) Franke (2015a). Acute toxicity of BAS 750 F to the honeybee Apis mellifera

L. under laboratory conditions. BASF Registration Document Number (Doc

ID): 2015/1128674.





213 with no significant deviations. It was noted that the reported relative

humidity (45-67%) fell below guideline recommendations (50-70%), though

as the study validity criteria were met this is not considered to have had a

significant effect on the outcome of the study. It was also noted that the

control treatments included a 50% w/v sucrose solution only and a 50% w/v

sucrose solution with 1% v/v Tween®80 and 1% v/v acetone. For

completeness it would have been appropriate to include controls consisting of

the sucrose solution with separate solvents. However, as there was zero

mortality in the two controls and the treated groups, this is not considered to

be important.

Conclusion Acute oral LD50 (48-hrs) >100 µg ai/bee


Table 107: Acute toxicity to bumble bees: active ingredient (supporting study)

Study type Acute toxicity to bumble bees (oral and contact)

Species Bumble bee, Bombus terrestris L.


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Endpoint Acute oral and contact LD50 (96-hrs)

Value Acute oral LD50 (96-hrs) >195.4 µg ai/bee


Reference (4.6.54) Amsel (2015a). Acute toxicity of BAS 750 F to the bumblebee Bombus

terrestris L. under laboratory conditions. BASF Study Identification Number:




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Comments The following comments were stated in the DAR:

Oral toxicity

The study was carried out according to GLP. Currently no official guideline for

acute toxicity of an active substance/formulation to bumblebees is in

circulation, therefore the HSE evaluator has made reference to the (yet to be

noted) EFSA guidance, as well as the supplemental papers referred to by the

applicant, in assessing the study. With reference to available guidance, no

significant deviations were noted. No guidance was available regarding the

appropriate sensitivity range for the reference item Dimethoate, although

research by Hanewald et al. (2014) indicates oral 96-hr LD50 of approximately

0.2-2.4 μg/bee (mean 1.2 μg/bee). The study report states an appropriate

range for the oral test as between 0.25 and 1.50 μg ai/bee (not referenced,

lending a degree of uncertainty to this range) and the 48-hr and 96-hr LD50

both fall within this range (being 0.56 and 0.53 μg ai/bee, respectively).

Altogether this suggests that this batch of bees could be quite sensitive, but

this sensitivity falls within available ranges. No mortality occurred in the

controls, which meets the validity criteria in OECD 213 and EFSA guidance

(<10% average control mortality). On balance, the study is considered to be

reliable.

Contact toxicity

The study was carried out according to GLP. Currently no official guideline for

acute toxicity of an active substance/formulation to bumblebees is in

circulation, therefore the HSE evaluator has made reference to (yet to be

noted) EFSA guidance, as well as the supplemental papers referred to by the

applicant, in assessing the study. With reference to available guidance, no

significant deviations were noted. No guidance was available regarding the

appropriate sensitivity range for the reference item Dimethoate, although

research by Hanewald et al. (2014) indicate an acute contact LD50 (96-hrs) of

approximately 1.2-7.5 μg/bee (mean 5 μg/bee). The study report states an

appropriate range for the contact test as between 10.0 and 2.50 μg ai/bee,

however as this range is not referenced there is a degree of uncertainty with

it. The 96-hr LD50 falls within this range (being 4.8 μg ai/bee), and is close to

the mean contact LD50 derived from the Hanewald et al. (2014) paper. This

suggests that this batch of bumblebees displays average sensitivity. No

mortality occurred in the controls, which meets the validity criteria in OECD

214 (<10% average control mortality). On balance, the study is considered to

be reliable.

It is also noted in the DAR that these two studies are provided as additional

information but not used in risk assessment.

Conclusion Acute oral LD50 (96-hrs) >195.4 µg ai/bee


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Table 108: Acute toxicity to honey bee larvae: active ingredient (key study)

Study type Acute toxicity to honey bee larvae


Flag Key study


Endpoint LD50, LC50, NOED and NOEC (96-hrs)

Value LD50 (96-hrs, acute) = 43.9 µg ai/larva

LC50 (96-hrs, acute) = 1.295 g ai/kg food

NOED (96-hrs, acute) = 29.7 µg ai/larva

NOEC (96-hrs, acute) = 0.875 g ai/kg food

Reference (4.6.58) Kleebaum (2015b). Acute toxicity of BAS 750 F to honeybee larvae (Apis

mellifera L.) under laboratory conditions (in vitro). BASF Study Identification

Number: 433204. BASF Registration Document Number (Doc ID):

2013/1235087.



Comments It was noted in the DAR that the mortality in two of the solvent control

replicates was greater than 15% (being 16.7%) after 72 hours; the non-

solvent control mortality mirrored this after 96 hours. The RMS evaluator

considered this to be an acceptable deviation as a) the exceedance of the

limit was only by 1.7%, b) the mean mortality was ≤15%, and c) the larval

grafting procedure integral to the assay is thought to make reliably

maintaining low levels of mortality in the controls a difficult task. The study is

considered to be valid therefore.

Conclusion LD50 (96-hrs, acute) = 43.9 µg ai/larva

LC50 (96-hrs, acute) = 1.295 g ai/kg food

NOED (96-hrs, acute) = 29.7 µg ai/larva

NOEC (96-hrs, acute) = 0.875 g ai/kg food

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Chronic toxicity to pollinators

Table 109: Chronic toxicity to honey bee larvae: active ingredient (disregarded study)

Study type Chronic toxicity to honey bee larvae


Flag Disregarded (see comments)


Endpoint EC50, ED50, NOEC and NOED (21 days)

Value Study deemed not reliable

Reference (4.6.59) Royer (2015a). BAS 750 F (Reg. No. 5834378) - Honey bee larvae test

(repeated exposure, observation 21 days) under laboratory conditions (in

vitro) - Non-GLP. BASF Registration Document Number (Doc ID):

2014/1327676.



Comments This study was not considered suitable for use in the risk assessment as

stated in the DAR. This was due to the following reasons:

The study was not carried out according to GLP, and according to Regulation

EC 283/2013 GLP is a requirement for all studies to be used in risk

assessments. The study follows the OECD ‘Draft Guidance document for

Honey Bee larval toxicity test, repeated exposure’, with a number of

deviations that add an element of uncertainty to the results derived.

Firstly it was noted that no reference item was tested alongside the test

substance. This means that the sensitivity of the test system cannot be

confirmed, and also that the study does not meet the drafted validity criteria.

Secondly, it was noted that fewer than 12 larvae were selected from two of

the colonies (8 each), whilst 32 larvae were selected from the other colony.

Guidance states that a minimum of 12 larvae from each colony should be

selected. That this condition has not been met reduces the statistical power

of the findings.

The apparently repellent effect of the test substance at the concentration of

325 mg ai/kg diet is noted.

Overall given the lack of GLP certification, and the failure to meet the study

validity criteria in draft guidance, the study is not considered suitable for risk

assessment.

The EPA agrees with this reasoning.

Conclusion Study deemed not reliable

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Appendix K: Standard terms and abbreviations

Abbreviation Definition

ai active ingredient

ADE Acceptable Daily Exposure

ADI Acceptable Daily Intake

AOEL Acceptable Operator Exposure Level

BBCH Biologische Bundesanstalt, Bundessortenamt und CHemische Industrie

BCF BioConcentration Factor

Bw body weight

CAS # Chemical Abstract Service Registry Number

cm centimetres

CoA Certificate of Analysis

CRfD Chronic Reference Dose

DDD Daily Dietary Dose

DT50 Dissipation Time (days) for 50% of the initial residue to be lost

dw dry weight

EbC50 EC50 with respect to a reduction of biomass

EC European Commission

EC25 Effective Concentration at which an observable adverse effect is caused in 25 %

of the test organisms

EC50 Effective Concentration at which an observable adverse effect is caused in 50 %

of the test organisms

EEC Estimated Environmental Concentration

EEL Environmental Exposure Limit

EFSA European Food Safety Authority

ErC50 EC50 with respect to a reduction of growth rate (r)

ER50 Effective Residue concentration to 50% of test organisms

FAO Food and Agriculture Organization

g grams

GAP Good Agricultural Practice

GENEEC Generic Estimated Environmental Concentration

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ha hectare

HQ Hazard Quotient

Kd partition (distribution) coefficient

Koc organic carbon adsorption coefficient

Kow octanol water partition coefficient

Kg Kilogram

L litres

Lb pounds

LC50 Lethal Concentration that causes 50% mortality

LD50 Lethal Dose that causes 50% mortality

LOAEC Lowest Observable Adverse Effect Concentration

LOAEL Lowest Observable Adverse Effect Level

LOC Level Of Concern

LOD Limit Of Detection

LOEC Lowest Observable Effect Concentration

LOEL Lowest Observable Effect Level

LR50 Lethal Rate that causes 50% mortality

M Molar

m3 cubic metre

MAF Multiple Application Factor

μm micrometre (micron)

mg milligram

μg microgram

mol mole(s)

MSDS Material Safety Data Sheet

NAEL No Adverse Effect Level

ng nanogram

NOAEC No Observed Adverse Effect Concentration

NOAEL No Observed Adverse Effect Level

NOEC No Observed Effect Concentration

NOEL No Observed Effect Level

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OECD Organisation for Economic Cooperation and Development

PDE Potential Daily Exposure

PEC Predicted Environmental Concentration

PHI Pre-Harvest Interval

pKa Acid dissociation constant (base 10 logarithmic scale)

PNEC Predicted No Effect Concentration

POW Partition coefficient between n-octanol and water

ppb parts per billion (10-9)

PPE Personal Protective Equipment

ppm parts per million (10-6)

REI Restricted Entry Interval

RPE Respiratory Protective Equipment

RQ Risk Quotient

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Appendix L: References

APVMA (2010). "Standard spray drift risk assessment scenarios."

Department Of Conservation (DOC) (2014). Conservation status of New Zealand earthworms, 2014.

EC (2017). Draft Assessment Report prepared according to the Commission Regulation (EU) N

1107/2009 - BAS 750F (Mefentrifluconazole)

EC (2019). FINAL Review report for the active substance mefentrifluconazole. Brussels, European

Commission, Directorate General for health and food safety.

EFSA (2009). "Risk Assessment for Birds and Mammals." EFSA Journal 7(12): 1438.

EFSA (2013). "Guidance on tiered risk assessment for plant protection products for aquatic organisms

in edge-of-field surface waters." EFSA Journal 11(7): 3290.

EFSA (2015). "Outcome of the pesticides peer review meeting on general recurring issues in

ecotoxicology." EFSA Supporting Publications 12(12): 924E.

EFSA (2018). "Peer review of the pesticide risk assessment of the active substance BAS 750 F

(mefentrifluconazole)." EFSA Journal 16(7): e05379.

EPA (2018). Risk Assessment Methodology for Hazardous Substances ; Draft for Consultation.

HSNO

Kim Y., D. N., Nowie M., Robinson B., Boyer S. (2017). "Molecular identification and distribution of

native and exotic earthworms in

New Zealand human-modified soils." New Zealand Ecological Society(41(2)).

PMRA (2019). Proposed Registration Decision - Mefentrifluconazole and related end-use products.

Ottawa, Pest Management Regulatory Agency: 208.

US EPA (2019). Mefentrifluconazole: Section 3 Environmetal Fate and Ecological Risk Assessment.

EPA–HQ–OPP–2018–0002-0032: 194

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Appendix M: Confidential Composition

The composition of Revystar® Fungicide is listed in Table 69.

Table 69: Detailed composition of Revystar® Fungicide

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app203766 revystar® fungicide...hazard classification of revystar® fungicide 2.4. the hazard...

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