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Lonza GmbH

RMS: Italy

Didecylmethylpoly(oxyethyl)

ammonium Propionate

June 2008

Doc I_ Evaluation Report

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Directive 98/8/EC concerning the placing biocidal products on the market

Inclusion of active substances in Annex I or IA to Directive 98/8/EC

Document I

Evaluation Report

Didecylmethylpoly(oxyethyl)ammonium Propionate

Product-type 8 (Wood preservative)

Rapporteur Member State: Italy

Draft June 2008

Lonza GmbH

RMS: Italy Didecylmethylpoly(oxyethyl)ammonium

Propionate June 2008


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CONTENTS

1. PURPOSE FOR WHICH THE COMPETENT AUTHORITY REPORT WAS PREPARED ............................................................................................................... 4

1.1. Introduction ..................................................................................................... 4

1.2. Applicant of the active substance................................................................... 4

1.3. Manufacturer of the active substance and product(s) ................................. 4

1.4. Acceptance of the dossier and evaluation work............................................ 4

2. OVERALL SUMMARY AND CONCLUSIONS ................................................... 5

2.1. Presentation of the Active Substance ............................................................ 5

2.1.1. Identity, Physico-Chemical Properties & Methods of Analysis........ 5

2.1.2. Intended Uses and Efficacy ............................................................... 9

2.1.3. Classification and Labelling .............................................................. 9

2.2. Summary of the Risk Assessment ................................................................ 11

2.2.1. Human Health Risk Assessment..................................................... 11

2.2.1.1. Acute effects...................................................................................... 11

2.2.1.2. Repeated dose effects ........................................................................ 12

2.2.1.2. Medical data ...................................................................................... 13

2.2.1.3. Exposure assessment ......................................................................... 13

2.2.1.4. Risk characterisation ......................................................................... 16

2.2.2. Environmental Risk Assessment ..................................................... 18

2.2.2.1. Fate and distribution in the environment.......................................... 18

2.2.2.2. Effects on environmental organism.................................................. 19

2.2.2.3. Environmental exposure assessment ............................................... 21

2.2.2.4. Risk characterisation for the environment ....................................... 23

2.2.3. List of endpoints ............................................................................... 26

3. PROPOSAL FOR THE DECISION ................................................................... 26

3.1. Background to the Decision.......................................................................... 26

3.2. Proposed Decision regarding Inclusion in Annex I................................... 27

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3.3. Elements to be taken into account by Member States when authorising products.......................................................................................................... 28

3.4. Requirement for further information ......................................................... 28

3.5. Updating this Evaluationt Report................................................................ 29

APPENDIX I: LIST OF ENDPOINTS ......................................................................... 30

Chapter 1: Identity, Physical and Chemical Properties, Classification and Labelling ........................................................... 30

Chapter 2: Methods of Analysis ........................................................ 32

Chapter 3: Impact on Human Health ............................................... 34

Chapter 4: Fate and Behaviour in the Environment....................... 37

Chapter 5: Effects on Non-target Species........................................ 39

Chapter 6: Other End Points ............................................................. 40

APPENDIX II: LIST OF INTENDED USES .............................................................. 41

APPENDIX III: LIST OF STUDIES ............................................................................ 42

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1. PURPOSE FOR WHICH THE COMPETENT AUTHORITY REPORT WAS PREPARED

1.1 Introduction

The Competent Authority (CA) Report was prepared on a dossier for the existing biocidal active substance, Didecylmethylpoly(oxyethyl)ammonium Propionate (Bardap 26)), according to the procedures of Biocidal Products Directive 98/8/EC, as a part of the review programme referred to in Article 16(2) of the Directive. This Document I and the supporting Documents IIA, IIB, IIC, IIIA, IIIB and the Confidential Annex. have been prepared by the Istituto Superiore di Sanità in support of the decision to include Didecylmethylpoly(oxyethyl)ammonium Propionate, as a wood preservative (product type 8), in Annex I of the Directive. This draft report is still to peer-reviewed by other Member State and the Commission. 1.2 Applicant of the active substance

Lonza GmbH Morinstrasse 32 DE-42041 Wuppertal Germany

Phone: 0049 202 245380 Fax: 0049 202 2453830 [email protected]

1.3 Manufacturer of the active substance and product (s)

Clariant GmbH Werk Gendorf DE-84508 Burgkirchen Germany

Phone: 0049 867970 Fax: 0049 86794545

1.4 Acceptance of the dossier and evaluation work

On 28th March 2004, the Italian Competent Authority received a dossier from the applicant. The Rapporteur Member State accepted the dossier as complete for the purpose of the evaluation on 28th September 2004. On 27th June 2005 the time period was suspended, the evaluation taken up again on 27th March 2006 and was stopped on 27th June 2006 in order obtained to the applicant the necessary data requested. After that, the evaluation phase was suspended again on the 27th June 2007 and taken up on 31th October 2007. During the evaluation period communication between the RMS and the applicant has resulted in revised documents at all document levels

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2 OVERALL SUMMARY AND CONCLUSIONS

2.1 Presentation of the Active Substance

The applicant claimed for the possibility to read across data from Didecyldimethylammonium chloride (DDAC) to Didecylmethylpoly(oxyethyl)ammonium Propionate (Bardap 26) with regard to several studies of toxicology, environmental fate and behaviour and ecotoxicology. The proposal for read across has been accepted and the rationale behind the acceptance is reported in Doc IIIA in the respective sections.

With regard to ecotoxicology only, the text of the agreed justification for read across is reported in Appendix I to the Doc IIA.

2.1.1. Identity, Physico-Chemical Properties & Methods of Analysis

Identification of the active substance

CAS-No. 94667-33-1

EINECS-No. None assigned

Other No. (CIPAC, ELINCS) None assigned

IUPAC Name alpha.-[2-(Didecylmethylammonio)ethyl]-.omega.-hydroxy-poly(oxy-1,2-ethanediyl) propionate

Chemical Name (CAS Index name) Poly(oxy-1,2-ethanediyl), .alpha.-[2-(didecylmethylammonio)ethyl]-.omega.-hydroxy-, propanoate

Common name, synonyms Didecylmethylpoly(oxyethyl)ammonium Propionate; N,N-Didecyl-N-methyl-poly(oxyethyl)ammonium Propionate, Bardap 26, Bardap 26 AS, DMPAP (internal abbreviation for the active substance), Dodigen 3519 (synonym of toll manufacturer for Bardap 26), Dodigen 3519 AS (active substance name of toll manufacturer), P4140 (old internal company code of applicant), LZ1524.1 (new internal company code of applicant)

Molecular formula C26H55NO3(C2H4O)n where n = 0 – 3

Structural formula

n = 0 – 3

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Molecular weight (g/mol) 437.777 (mean value)

MWs used: C=12.011; H=1.00794; N=14.0067; O=15.999 No. of oxyethyl moieties (1) MW Relative % distribution MW individual Monomer (1) 429.726 0.84 360.970 Dimer (2) 473.779 0.15 71.067 Trimer (3) 517.832 <0.01 5.178 Tetramer (4) 561.885 <0.001 0.562 MW TOTAL: 437.777

Purity 90 – 99 % (solvent-free) Clarification required by RMS

Impurities The full details are confidential and can be found in the Annex of Confidential Data

Since differing information have been provided in Doc. IIIA Section 2 with regard to the a.s. purity and the content of the impurities, clarification is required.

Identification of the representative product

Trade name Korasit KS (Lonza AG)

SPU-01840-F-0-SL (Spiess Urania Chemicals GmbH)

Manufacturer's development code number(s) None assigned

Active substances Didecylmethylpoly(oxyethyl)ammonium propionate; Copper carbonate, basic

Content of the active substances 84 g/kg of Didecylmethylpoly(oxyethyl)- ammonium propionate (120 g/kg as Bardap 26); others details can be found in the Annex of Confidential Data 152 g/kg of Copper carbonate, basic; others details can be found in the Annex of Confidential Data

Function Fungistatic and insecticide

Physical state of preparation Liquid

Nature of preparation Solution

Physico-Chemical Properties

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Didecylmethylpoly(oxyethyl)ammonium propionate (CAS 94667-33-1) is a quaternary ammonium compound. According to the Applicant, the solvent-free a.s. is typically 90–99 % pure with several impurities (see Annex of Confidential Data). Physico-chemical properties (with the exception of Doc IIIA 3.4, 3.8, and 3.17) were studied for Bardap26 AS/Dodigen 3519, which is didecylmethylpoly(oxyethyl)ammonium propionate 93.5% w/w pure, prepared by removal of process solvents (diol/water) from a typical production process.

Didecylmethylpoly(oxyethyl)ammonium propionate is a yellow liquid with a relative density D4

20 of 0.942. No freezing point is observed down to -50°C, whereas boiling ranges from 180 to 195 ºC. Its vapour pressure, extrapolated from the experimental vapour pressure curve Log Pvap vs. 1/T, is 1.8E-06 Pa, 4.0E-06 Pa, and 1.4E-05 Pa at 20 °C, 25 °C, and 50 °C, respectively. The Henry’s law constant (1.03E-011 and 4.72E-13 Pa m3/mol for the monomer and the dimer, respectively) has been estimated by QSAR using HENRYWIN v 3.10 model. The structure of the a.s. is confirmed by absorption spectra (UV/Vis, IR, NMR) and mass spectrum. Didecylmethylpoly(oxyethyl)ammonium propionate is completely miscible in water in the pH range 5-9 at room temperature, as well as in ethanol and octanol (solubility > 250 g/l at ca. 20°C in either case). Since the active substance is irreversibly ionised, no dissociation constant can be determined. Partition coefficient is not determinable, either. EC method A.8 is not applicable for surface-active substances such as didecylmethylpoly(oxyethyl)ammonium propionate. Also assessment by KOWWIN is considered inaccurate, being the software database very limited for surfactants. On the other hand, log Pow can be roughly obtained from solubility in pure n-octanol and water (log Pow ≈ 0). However, this calculation is of no use with regard to environmental fate & behaviour and secondary poisoning risk (experimental BCF available). Since no decomposition or chemical transformation is observed below 150°C, didecylmethylpoly(oxyethyl)ammonium propionate can be considered stable. Didecylmethylpoly(oxyethyl)ammonium propionate has proved to have an auto-ignition temperature of 264 °C, with a flash point of 134 °C. On the basis of experience in use and/or structural formula (absence of reactive groups), it does not show explosive properties or oxidizing properties. Didecylmethylpoly(oxyethyl)ammonium propionate has also proved to be a non-newtonian fluid (dynamic viscosity: 3000 mPa⋅s and 400 mPa⋅s at 20 and 40 °C, respectively). Polyethylene, Type Hostalen GM 6255, 7745 and 7746, has proved to be resistant against the test material [Bardap26 (70 % a.s. in 18% polyethylene glycol, 10% polyethylene glycol and water)]. Experience in use showed that 316 l stainless steel is satisfactory at optimum handling temperatures [for higher temperatures: stainless steel containing 6% or more molybdenum (Rolled alloys AL-6XN, Avesta 254-SMO, INCO 25-6MO)]. PVC, polyolefin, Teflon, Kynar, Kalrez and vinyl ester are satisfactory to temperatures recommended by manufacturer. Natural rubber, neoprene and Buna-N should be avoided. There is no risk to be expected due to physical-chemical properties of the formulated product Korasit KS, either.

Analytical Methods

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The RMS is waiting for the submission of a study report in progress specific for the active substance. The HPLC-ELSD and GC-FID analytical methods submitted for substances different from didecylmethylpoly(oxyethyl)ammonium propionate have not be considered or commented by RMS, since not pertinent to the active substance.

Didecylmethylpoly(oxyethyl)ammonium propionate was also screened by ion chromatography, but the method cannot be considered acceptable by the RMS. No validation work has been carried out for the a.s. or the impurities detected. In particular, no qualitative/quantitative analysis has been performed; no data on linearity have been provided, either. As far as chromatograms are concerned, no peak-assignment has been accomplished.

In conclusion, a specific analytical method for the identification/quantification of the a.s. [didecylmethylpoly(oxyethyl)ammonium propionate] and impurities >1g/kg is deemed necessary. Full validation in compliance with TNsG (chapter 2, 4.1) is required.

The screening by ion chromatography commented above has been proposed by the Applicant also for the determination of the a.s. in the biocidal product (Korasit KS) in a justification for non-submission of data. The method is not deemed acceptable by RMS (see comments above) and, hence, neither is the justification provided. In conclusion, an analytical method for the identification/quantification of the a.s. in Korasit KS is required. Full validation in compliance with TNsG is required.

Please, also note that according to TNsG in case of a preparation such as Korasit KS containing more than one a.s., a method capable of determining each, in the presence of the other, should be provided. If a combined method is not submitted, the technical reasons must be stated.

LC-MS methods have been used for the determination of residues of the active substance in soil and water down to a level of 0.01 mg/kg and 0.1 µg/l, respectively. Both methods are sufficiently specific, linear, accurate and precise and, therefore, are deemed acceptable.

No analytical method is required for the determination of residues in air, since the a.s. is non-volatile and will not be used in spray application.

No analytical method is deemed necessary for the determination of residues in body fluids and tissues, being the a.s. is neither toxic nor highly toxic.

Wood treated with didecylmethylpoly(oxyethyl)ammonium propionate-containing biocidal product is not intended for and contains label restrictions against use in areas where food for human consumption is prepared, consumed or stored, or where the feedingstuff for livestock is preprared, consumed or stored. Therefore, no analytical method for the determination of residues in food/feed of plant/animal origin is required, either.

2.1.2. Intended Uses and Efficacy

Didecylmethylpoly(oxyethyl)ammonium propionate (Bardap26) acts as a fungistatic and an insecticide. It is a cationic surfactant type active substance. Since it is surface active, it has fair wetting properties and reacts strongly with cell walls of micro-organisms. Due to its interaction with phospholipid-bilayer structures, it severely alters the cell wall permeability, disturbs membrane-bound ion-translocation mechanisms, and may facilitate the uptake of other biocides. The field of application of Didecylmethylpoly(oxyethyl)ammonium propionate includes wood

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preservatives for the preventive treatment against wood destroying organisms and against wood discolouring moulds and fungi. Didecylmethylpoly(oxyethyl)ammonium propionate is used for preventive protection of wood and constructional timbers in hazard classes 1 to 4A according to ISO draft standard The use concentration depends on the type of application technique, use class required and on additional formulation components. The biocidal product KORASIT KS (Didecylmethylpoly(oxyethyl)ammonium Propionate ,is a aqueous solution, with preventive efficacy against wood destroying (basidiomycetes) ,against soft rot fungi and insects . It is used in drenching/dipping and vacuum pressure process applications in wood protection as a fungistatic/insecticide. The fungicidal effect depends on Didecylmethylpoly(oxyethyl)ammonium propionate (and copper as co-biocide). The insecticidal effect depends on Didecylmethylpoly(oxyethyl)ammonium propionate. The biocidal product concentrate is diluted to a suitable working strength with water. The degree of dilution will vary depending on the wood species, type of wood product and anticipated use. The requirements for the final concentration of Didecylmethylpoly(oxyethyl)ammonium propionate vary between 0.1% and 0.7%. An uptake of 3 to 6 kg/m3 of product resp. 40 to 60 g/m2 should be achieved by the above application methods, which is in terms of Didecylmethylpoly(oxyethyl)ammonium propionate typically between 0.5 and 0.7 kg/m3 in multiple a.i. containing wood preservatives. Against fungi, there exists a selective activity spectrum. From practical experiences with standalone-biocides in this field of application it is known that a local formation of “resistant” fungus strains at the application site may occur. For this reason Bardap26 or other biocides are normally not used as unique biocide in anti sapstain formulations. This preservative type is always made up of two or three different biocides to avoid adaptations or resistances. Additional investigations on exposure of domestic microbial communities to quaternary ammonium biocidal substances does not result in increased antimicrobial resistance (McBain A.J. et al. (2004)).

2.1.3. Classification and Labelling

Didecylmethylpoly(oxyethyl)ammonium Propionate is currently not classified according to Annex I of Council Directive 67/548/EC. Based on the results from studies presented in the dossier, classification of Didecylmethylpoly(oxyethyl)ammonium Propionate was proposed according to the criteria set out in Directive 67/548/EEC( with amendments), 99/45/EC (with successive adaptations) and 2006/8/EC

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2.1.3.1 Proposal for the classification and labelling of the active substance

On the basis of review of the submitted data, specific concentration limits have been proposed for the environmental classification Class of danger C; triggered by R50

Risk phrases R22 Harmful if swallowed

R34 Causes burns

R50 Very toxic to aquatic organisms Safety phrases S1/2 Keep locked up and out of reach of children

S26 In case of contact with eyes, rinse immediately with plenty of water and seek medical advice

S28 After contact with skin, wash immediately with plenty of soap and water

S29 Do not empty into drains.

S36/37/39 Wear suitable protective clothing, gloves and eye/face protection

S45 In case of accident or if you feel unwell, seek medical advice immediately (show the label where possible)

S60 This material and its container must be disposed of as hazardous waste

S61 Avoid release to the environment. Refer to special instructions/ safety data sheets

Specific limits Specific concentration limits for the environmental classification

Cn ≥ 2.5%: N; R50

2.1.3.2 Proposal for the classification and labelling of the product: Korasit KS

Class of danger Xn; N

Risk phrases R20/21/22 Harmful by inhalation, in contact with skin and if swallowed.

R38 Irritating to skin.

R 41 Risk of serious damage to eyes

R50/53 Very toxic to aquatic organisms, may cause long-term adverse effects in the aquatic environment

Safety phrases S2; Keep out of the reach of children

S13; Keep away from food, drink and animal foodstuffs.

S20/21; When using do not eat, drink or smoke

S26; In case of contact with eyes, rinse immediately with plenty of

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water and seek medical advice

S29 Do not empty into drains

S39; Wear eye/face protection.

S46; If swallowed, seek medical advice immediately and show container or label.

S60; This material and its container must be disposed of as hazardous waste.

S61; Avoid release to the environment. Refer to special instructions/safety data sheets

2.2. Summary of the Risk Assessment

2.2.1 Human Health Risk Assessment

2.1.1.1. Acute effects

Didecylmethylpoly(oxyethyl)ammonium Propionate (Bardap26) is highly ionic and, therefore, it is expected not to be readily absorbed from the gastrointestinal tract or skin. No specific studies on Bardap26 toxicokinetics and metabolism are available, however, the read across from data on a structurally related compound, namely Didecyldimethylammonium Chloride (DDAC), has been accepted. The rationale for the read across acceptance is explained in details at the beginning of Doc.IIIA- Section 6. Less than 3% of an oral dose of DDAC was eliminated via urine following a single oral dose, whereas more than 90% is excreted in the faeces. Although it was not possible to discriminate between unabsorbed/absorbed material, based on the chemical nature of the test substance it can be anticipated that about 90% is present in faeces as unabsorbed material. On the basis of these data on DDAC, it is expected that Bardap26 oral absorption is limited to ≈10%. The majority of DDAC metabolism is expected to be carried out by intestinal flora giving rise to hydroxylation products in the alkyl chain. About 0.1% of a DDAC dose delivered as aqueous solution fully penetrated human skin in vitro in 24 h; mean total DDAC absorbed was 9.41%,(rounded to 10% for risk characterization purposes), including the radioactivity present in the dermis and epidermis at the dose site. The lowest determined oral LD50 value for Didecylmethylpoly(oxyethyl)ammonium Propionate is 662 mg/kg. There was a dose-related increase in mortality. Clinical signs included hypoactivity, irregular/shallow breathing, ano-genital staining and diarrhoea. Gross necropsy findings in decedents included discoloured liver, red lungs and fluid-filled stomach. The active substance is classified as ‘Harmful if swallowed’ on the basis of this study and is assigned the symbol Xn and risk phrase R22. A acute dermal toxicity study was not available on Bardap26, and data on DDAC were considered fully valid. The rabbit acute dermal LD50 of Didecyldimethylammonium Chloride is 3342 mg/kg . DDAC caused skin irritation at the dose site in all animals. Didecyldimethylammonium Chloride is corrosive to dermal tissue and only moderately toxic systemically by the dermal route.

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Didecylmethylpoly(oxyethyl)ammonium Propionate is not volatile as the vapour pressure is 1.8x 10-6 Pa2. Thus, inhalation of N,N-Didecyl-N-methyl-poly(oxyethyl)ammonium Propionate is not considered a potential route of exposure. Didecylmethylpoly(oxyethyl)ammonium Propionate induced severe erythema, desquamation and corrosive eschar in the rabbit skin, and it is therefore classified as corrosive to skin, requiring R34 as risk phrase. Didecylmethylpoly(oxyethyl)ammonium Propionate is also irritant to eye N,N-Didecyl-N-methyl-poly(oxyethyl)ammonium Propionate is not a skin sensitiser.

2.2.1.2. Repeated dose effects

Didecylmethylpoly(oxyethyl)ammonium Propionate intake in the diet over 90-days did not result in death in rodents. No clinically observable signs of toxicity were detected. However at high dietary administration dose level, evident toxicity is noted in rat; reduction in body weight gain, food consumption, clinical chemistry changes, small spleen in females, reduced absolute liver weight and body weight relative liver weight. The NOEL was equivalent to 90 mg a.s./kg/day and the LOEL was 275 mg a.s./kg/day Subchronic oral toxicity studies on a non rodent species, dermal toxicity studies in rodents and chronic toxicity/carcinogenicity study have not been conducted on Didecylmethylpoly(oxyethyl)ammonium Propionate, however they have been conducted using the structurally related compound Didecyldimethylammonium Chloride (DDAC). The read across from data on DDAC has been accepted. The rationale for the read across acceptance is explained in details at the beginning of Doc.IIIA- Section 6. In a 1-year feeding study in dogs with Didecyldimethylammonium Chloride, the two highest doses (10 and 20 mg/kg/day) resulted in g.i.-related complications including emesis and abnormal faeces, resulting in death of 2 out of 4 animal at 20 mg/kg/day. The clinical signs observed in all the animals treated at 10 mg/kg/d (emesis, salivation, soft/loose faeces) persisted for the entire study duration; taking into account that the treatment dosage is reached with 2 different administrations within the day (lowering the entity of the bolus dose achievable with a single administration-possibly giving rise to more severe effects) this dosage cannot be considered as the NOAEL derived from the study. The NO(A)EL should be fixed equal to 3 mg/kg/d, related to local effects on gut mucosa. The clinical signs reported at 10 mg/kg/d, on which the NOAEL derivation is based, are consistent with the irritation/corrosive properties of the test item: only a small amount of DDAC becomes systemically available, without giving rise to any significant systemic effects. The systemic effects (10-15% decrease in body weight), were seen at 20/30 mg/kg/d, although secondary to effects in the gut. Therefore it is not appropriate to use 3 mg/kg/d to derive a systemic AEL and consequently for AEL calculation it is proposed to use the immediately higher value (systemic NOAEL=10 mg/kg/d).

The NOAELs for non neoplastic effects after chronic dietary DDAC administration were 32-41 mg/kg/day for rats and 76 – 93 mg/kg/day for mice. NOAELs values derivation was mainly based on aspecific effects, such as decreased body weights, considered to be secondary to local effects on gut mucosa and intestinal microflora. No organ specific toxicity was evidenced. In line with the fact that the main outcome directly derives from the irritative/corrosive properties of the

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active substance, the subchronic and chronic NOAELs are similar in rodents, and little difference is expected between the 2 exposure scenario. Adequate studies evaluating teratogenicity and adequate two-generation study have been conducted on the chemical and structural analog, Didecyldimethylammonium Chloride. Didecyldimethylammonium Chloride does not affect reproduction or development at doses that are not toxic to the mother.In view of the chemical and structural similarities, the available data was considered appropriate for Didecylmethylpoly(oxyethyl)ammonium Propionate, taking into account both the chemical and structural similarities and the need for reducing unnecessary animal experiments. The NOAEL from maternal toxicity in the reproductive toxicity study was 1 mg/kg/d. It is not considered appropriate to use that NOAEL for systemic AEL derivation, since the administration was by gavage, and considering the local effects on the gut mucosa, it is obvious that a bolus dose is more irritant than the same amount taken slowly and mixed with the other dietary components, as it was in the 1-year dog study from which the relevant NOAEL is taken for risk characterization. Didecylmethylpoly(oxyethyl)ammonium Propionate produced no mutagenic activity in any screening studies including in vitro (bacterial or mammalian cell mutation, mammalian cell chromosomal aberration) and in vivo (bone marrow chromosomal aberration) studies. A carcinogenicity study using the chemical and structural analogue, Didecyldimethylammonium Chloride showed that the NOAELs for non neoplastic end-points were 32-41 mg/kg/day (750 ppm) for rats and 76-93 mg/kg/day (500 ppm) for mice. Didecyldimethylammonium Chloride did not result in an increase in tumors and was not considered oncogenic in either study. Thus, it is considered that Didecylmethylpoly(oxyethyl)ammonium Propionate will not be oncogenic The lack of any structural similarity to known neurotoxins or of any alert for neurotoxic effects, shown by quaternary ammonium chemicals in general, supports the conclusion that DDAC has no neurotoxic potential.

2.2.1.3. Medical data

No medical reports on the manufacturing personnel have been submitted.

2.2.1.4. Exposure assessment

The biocidal product containing the active substance is used in two wood preservative treatment applications: dipping and vacuum pressure processes. For both processes, the preservative is delivered to the processing plant by tanker in the form of a concentrate. The concentrate contains 8.4% of the active substance Didecylmethylpoly(oxyethyl)ammonium Propionate. It is diluted down to a suitable working strength with water. The degree of dilution varies depending on the wood species, type of wood product and anticipated use. N,N-Didecyl-N-methyl-poly(oxyethyl)ammonium Propionate concentrations in both processes vary between 0.1% and 0.7%.

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Furthermore, the use classes 1 to 4A are envisaged for the Didecylmethylpoly(oxyethyl)ammonium Propionate containing wood preservative product.

Professional exposure

There are four main strata of workers that may be exposed to the wood preservative in the process plant. For the purposes of modeling, the potential exposure routes are considered to be inhalation and skin contact. However, inhalation exposure is considered to be extremely limited based on the use of dilute aqueous solutions of the Bardap26, the low vapour pressure of the Bardap26, and the typical use patterns (dipping and vacuum pressure). It is assumed that respiratory protective equipment is used only in event scenarios such as the need to clear fallen wood within the treatment vessel.

As a worst case scenario, all calculations are based on the wood treatment solution employed containing 0.672% a.s. The neat concentrate of the substance (containing 8.4% a.s.) is only handled under closed conditions and so is modelled under Use Scenario 1.

Exposure calculations were performed according to the recommendations of the TNsG (Human Exposure to Biocidal Products, as revised by User Guidance version 1 (EC, 2002a). Model calculations have been undertaken using measured data given in the TNsG as revised in the user guidance and are considered to represent a reasonable scenario for risk assessment purposes. Dermal exposure has been assessed assuming clothing penetration of 10% (User Guidance version 1, p42), except for certain exposure scenarios (dipping and cleaning out dipping tank) where it is assumed that impenetrable coveralls will be worn (penetration = 4% - TNsG, Part 3, p60). The dermal penetration of Bardap26 used for this assessment is 9.41%, as discussed in Section 4.1 of this document. The default value for body weight of an exposed adult is assumed to be 60 kg in order to include women (50th Percentile = 60.3 kg according to ECETOC, 2001).

Table 2.2.1.4.-1 TNsG Models Predictions for Total Exposure to Bardap26 in Wood Preservation *

Exposure scenario PPE Systemic Uptake (mg)

Total Systemic dose (mg/kg/d)

Mixing and loading concentrate (8.4% solution)

Gloves, goggles, vapour masks 0.012 0.0002

Dipping (0.7% solution)


Vacuum/pressure treatment (0.7% solution)


* A correction has been also applied for the maximum dermal absorption of 9.41%.

Non-professional exposure (Consumers)

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Non-professional users are not involved in the application (wood treatment) stage. Non-professional exposure is restricted to handling of treated lumber in operations such as erecting fences. The level of exposure is considered to be comparable to occupation exposure to workers that handle treated wood after it is dry.

Indirect exposure as a result of use of the active substance in biocidal product

The secondary human exposure estimates consider the potential for the exposure of professional adults, infants and children in a number of possible scenarios in which they may come into contact with Bardap26 treated timbers.

Four main exposure paths were identified that are (a) acute by adults sanding treated timber (inhalation), (b) acute by infant ingesting wood particles (oral), (c) chronic by childrens playing on playground structure outdoors (dermal), (d) infants playing on weathered structure and mouthing (combined dermal and oral).

A summary of indirect exposure rates is provided in the following table.

Table 2.2.1.4.-2

Oral Dermal Inhalation Combined Acute

Adult sanding -- -- 0.0001 mg/kg/day -- Child

mouthing 0.007 mg/kg/day -- -- --

Chronic Child playing

0.00017

mg/kg/day

Infant playing 0.0023 mg/kg/day

0.00017 mg/kg/day

-- 0.0025 mg/kg day

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2.2.1.5. Risk characterisation

AEL (Acceptable exposure level)

The lowest NOAEL in a repeated does study is the one of 10 mg/kg b.w/day derived from the 52 weeks study on dogs with the read-across from chemical and structural analogue, Didecyldimethylammonium Chloride.

This value is then used in deriving the AEL. An assessment factor of 10 interspecies variability and 10 for taking into account intraspecies variability).

The AEL value corresponds to 0.1 mg/kg/day

Exposure and risk from use of the product

No potential risks are identified as shown in the table below with values derived by using the TNsG approach described in Doc. IIC. This is evident comparing the AEL with workers exposure values. Negligible exposure is predicted for consumers and man via the environment.

Risk Characterisation Calculations for Professional Users to Bardap26

Table 2.2.1.5.-1

USE SCENARIO

Estimated total uptake

(mg/kg/d)

(worst case)

AEL Approach

AEL/body dose

for workers, total uptake (dermal+inhalation) (AEL = 0.1 mg/kg/d)

% of the AEL

(AEL = 0.1 mg/kg/d)

Scenario 1 Mixing and loading concentrate (8.4% solution)

0.0002 0.002 0.2

Scenario 2 Dipping (0.7% solution)

0.003 0.03 3

Vacuum/pressure treatment (0.7% solution)

0.0055 0.055 5.5

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For the use scenarios the use of Bardap26 in the wood preservation process does not result in any significant risk for the workers due to intentional or repeated direct handling of the solutions. Conclusion: There is a no concern for industrial workers from dermal exposure during preparation of treatment solutions, dipping procedures.

Indirect exposure as a result of use

Indirect exposure to construction timber treated with wood preservatives is not directly related to the use of the wood preservative during application or handling of the wet treated wood, but to secondary exposure to the treated ready-to use wooden articles.

Four main exposure paths were identified that are (a) acute by adults sanding treated timber (inhalation), (b) acute by infant ingesting wood particles (oral), (c) chronic by childrens playing on playground structure outdoors (dermal), (d) infants playing on weathered structure and mouthing (combined dermal and oral). The calculations were performed an application rate of 0.7 kg a.s./m3. For the contact assessment of treated timber a worst case leaching rate of 0.65% per day was chosen.

The following toxicity data have been used for the risk characterisation and a MOS reference of 100 has been defined considering an assessment factor of 10 for interspecies differences and another assessment factor of 10 for taking into account intraspecies differences.

Acute: Oral acute LD50 = 662 mg/kg bw Dermal acute = use oral LD50 = 3342 mg/kg

Chronic: Systemic NOAEL = 10 mg/kg bw/d

The following MOS values have been calculated for the indirect exposure scenarios:

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Table 2.2.1.5.-2

Oral Dermal Inhalation Combined NOAEL/LD5

0 MoS

Acute a) Adult sanding -- -- 0.0001

mg/kg bw -- 662 mg/kg bw 6620000

b) Infant ingesting

0.007 mg/kg bw -- -- -- 662 mg/kg

bw 94571

Chronic

c) Childrens playing

0.00017 mg/kg bw/day

Systemic: 10 mg/kg bw/day

58824

d) Infants playing

0.0023 mg/kg bw/day

0.00017 mg/kg bw/day

0.0025 mg/kg bw/day

Systemic: 10 mg/kg bw/day

40000

MOS value are calculated by the ratio of the above reported toxicity data and the total daily uptake for humans (see section 3.2.4 – Doc. II B).

All the MOS calculated are above the MOS reference value. No risk is expected for indirectly exposed humans. Conclusion: The TNsG exposure scenario predicts that the use of Bardap26 as a wood preservative active substance poses negligible risk to humans from indirect exposure.

Combined exposure

Combined exposure to Bardap26 used in a wood preservative product is not expected to occur, since only industrial use is envisaged. Theoretically, a combined exposure scenario is possible when an operator, after the working day, inhales the volatile residues indoors at home. However, due to the low vapour pressure of the active substance, this latter exposure can be considered as negligible. For this reason combined exposure has not been quantitatively evaluated in this dossier.

.2.2.2. Environmental Risk Assessment

2.2.2.1. Fate and Distribution in the Environment

Biodegradation

Didecylmethylpoly(oxyethyl)ammonium propionate was found to be not readily biodegradable; it can be considered inherently biodegradable. A study to determinate aerobic biodegradation in a sewage treatment plant was not conducted since data were available for the structural analog Didecyldimethylammonium Chloride, which was found to biodegrade in aerobic conditions. At test termination (28 days) 93.3% of the radioactivity was evolved as 14CO2, 1.32% was recovered in the extracts and 3.28% remained in the solid. One major metabolite was identified. In the abiotic sample 92.22% of the

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radioactivity was recovered in the extracts and 1.5% remained in the solid. A biodegradation study in two water/sediment systems has been performed and shoed that the substance easily migrates from the aqueous phase to the sediment phase and is also easily adsorbed to sediments (high Koc). The degradation in the sediment phase did not increase very much after the first month and the DT50 of the total system was not reached within the 120 days test duration

Abiotic Degradation

Didecylmethylpoly(oxyethyl)ammonium propionate was hydrolytically stable during the 5 days hydrolysis study at pH 4, 7 and 9 at 50°C; half-lives were estimated as > 1 year. An adequate study evaluating phototransformation in water has been conducted on the chemical and structural analog, Didecyldimethylammonium Chloride. In view of the chemical and structural similarities, it is considered that the available data are adequate for Didecylmethylpoly(oxyethyl)ammonium propionate. Didecyldimethylammonium Chloride was found to be photolytically stable in the absence of a photosensitiser. The half-life of the test compound was determined to be 227 days (light, exposed) and 427 days (dark, exposed) with 7% degradation after 30 days.

Distribution

A study to determine adsorption and desorption in soil for Didecylmethylpoly(oxyethyl)ammonium propionate was not carried out as an adequate study has been conducted on the chemical and structural analog, Didecyldimethylammonium Chloride. In view of the chemical and structural similarities, it is considered that the available data is adequate for Didecylmethylpoly(oxyethyl)ammonium propionate. Didecyldimethylammonium Chloride was classified as immobile in four soil/sediment types with the adsorption (Kd) and mobility (Koc) coefficients of Kd=1,095 and Koc=437,805 for sand, Kd=8,179 and Koc=908,757 for sandy loam, Kd=32,791 and Koc=1,599,564 for clay loam, and Kd=30,851 and Koc=1,469,081 for silt loam (Ref No 1792).

Mobility

The results of the adsorption in soil study on a structural analog Didecyldimethylammonium chloride indicate little or no potential for mobility in soil and should not pose an environmental risk for contamination of ground water. Thus, it is considered that a short or a long-term Mobility- Lysimeter study is not justified.

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Bioaccumulation

Based on a measured BCFfish (81, read-across from DDAC data, see IIIA Section 7 introduction, IIA Appendix I) it is considered that Bardap26 has a low potential for bioaccumulation. No data are available on the BCFearthworm; calculation according to TGD (eq. 82d) is not applicable. Nevertheless, bioaccumulation in the terrestrial food chain would pose birds and mammals at risk of secondary poisoning in case of BCFearthworm in excess of 12672 and 25172, respectively (see IIA, 4.1.3; IIB, 3.3.5; IIIA, 7.5.5.1). In conclusion, terrestrial bioaccumulation cannot be estimated with the data available; however the risk of secondary poisoning via the terrestrial food chain is deemed unlikely.

2.2.2.2. Effects on Environmental Organisms

Aquatic Compartment

The results of acute toxicity studies indicate that Bardap26 is very toxic to fish, daphnia and algae. The most sensitive group is invertebrates (Daphnia 48-hour EC50 of 0.07 mg/l under semi-static conditions) whilst the less sensitive group is fish (common carp 96-hour LC50 of 0.62 mg/l under semi-static conditions). Bardap26 is harmful to microbial activity in STP, being this inhibited at concentration higher than any other aquatic group (3h respiration inhibition test EC50 of 16.8 mg/l). The results of long term toxicity studies come from a read-across with DDAC data (see IIIA Section 7 introduction, IIA Appendix I) which indicate that Bardap26 is expected to be very toxic to fish and daphnia. In a test performed under flow-through conditions, the 34d NOEC was 0.032 mg/l for Zebra fish with no effect on hatching. Daphnia magna was more sensitive than fish, with a 21d NOEC (survival) of 0.010 mg/l recorded under flow-through conditions. The PNECwater is derived from the lowest of the three NOECs (0.01 mg/l daphnia), leading to: PNECwater 0.001 mg/l.

Sediment

The hazard of Bardap26 to sediment dwelling organisms is based on DDAC data (read-across, see IIIA Section 7 introduction, IIA Appendix I). In a 28 days test with Chironomus tentans, the NOEC (survival) was 530 mg/kg dw, corresponding to 356.16 mg/kg wwt.

The PNECsediment is calculated from the long term NOEC available as: PNECsediment 3.56 mg/kg wwt.

Terrestrial Compartment

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The effect of Bardap26 on earthworms was assessed in an acute toxicity test with E. foetida. The 14-day LC50 was 4390 mg/kg dry soil, the NOEC was 2000 mg/kg dry soil. Based on DDAC data (read-across, see IIIA Section 7 introduction, IIA Appendix I) no effect of Bardap26 on nitrite, nitrate, ammonium and carbon dioxide formation is expected at a concentration of 1000 mg/kg dry soil. Based on DDAC data (read-across, see IIIA Section 7 introduction, IIA Appendix I) the EC50 for terrestrial plants is expected at 283 mg/kg dw (20 days growth test with mustard, mung bean and wheat), corresponding to an EC50 of 268.66 mg/kg wwt, corrected for the organic matter content. The acute Bardap26 LD50 for birds is observed at 226 mg/kg bw (northern bobwhite quail). Based on DDAC data (read-across, see IIIA Section 7 introduction), the short term dietary LC50 for birds is expected at > 5620 mg/kg (northern bobwhite quail and mallard). Bardap 26 is toxic to mammals with a NOEC value of 100 mg/kg in mice in a 18 months body weight gain test (read-across from DDAC data, see IIIA Section 6, IIA Section 3). The PNECsoil is derived from the EC50 plants as: PNECsoil 0.177 mg/kg wwt. The PNECbirds is derived from dietary toxicity studies as: PNECbirds 1.87 mg/kg food. The PNECmammals is derived from an oral (18 months) repeated doses study on mouse, leading to: PNECmammals 3.33 mg/kg food.

2.2.2.3. Environmental Exposure Assessment

In the following table has been reported the PECs calculated using the refinement values for the Use patterns 1-4 (realistic worst-case) and the default value for the Use pattern 5 (worst-case).

Aquatic Compartment Exposure assessment

Local PEC

Dipping application

PEClocalwater 0.0032 mg/l PEClocalsed 77.1 mg/kgwwt

PECmicroorganism STP 0.085 mg/l Storage of dipping/immersed wood

PEClocalwater 0.00059 mg/l PEClocalsed 14.2 mg/kgwwt Vacuum pressure application

PEClocalwater 0.00072 mg/l PEClocalsed 17.3 mg/kgwwt PECmicroorganism STP 0.0191 µg/l Storage of Vacuum pressure treted wood

PEClocalwater 0.00033 mg/l

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PEClocalsed 7.9 mg/kgwwt In situ-treatment

Clocalwater, brush (professionals) 0.0012 mg/l Clocalwater, brush (amateurs) 0.002 mg/l Clocalsed, brush (professionals) 28 mg/kgwwt Clocalsed, brush (amateurs) 47 mg/kgwwt

Terrestrial Compartment Exposure assessment

Local PEC

Storage of dipping/immersed wood

PEClocalsoil (after 30 days) 3.84 mg/kg PEClocalsoil (after 20 years) 935.3 mg/kg Storage of Vacuum pressure treated wood

PEClocalsoil 2.90 mg/kg In situ treatment

PEClocalsoil (professionals) 0.49 mg/kg PEClocalsoil (amateurs) 0.81 Treated wood in service Noise barrier

PEClocalsoil 0.12 mg/kg Treated wood in service House

PEClocalsoil 0.31 mg/kg Treated wood in service Transmission pole

PEClocalsoil 0.08 mg/kg Treated wood in service fence post

PEClocalsoil 0.02 mg/kg

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Atmospheric Compartment Exposure assessment

Local PEC

Dipping application

Annual average local PEC in air 2.55E-7 mg/m3 Vacuum pressure application

Annual average local PEC in air 2.86E-6mg/m3

2.2.2.4. Risk Characterisation for the Environment

Aquatic Compartment

PEC/PNEC values Use pattern

Water compartment Sediment compartment

Sewage treatment plant

Use pattern 1: Dipping treatment during application

3.2 21.7 0.51

Use pattern 2: Dipping treatment during storage

0.59 3.98 -

Use pattern 3: Vacuum pressure treatment during application

0.72 4.86 0.11

Use pattern 4: Vacuum pressure treatment during storage

0.33 2.2 -

Use pattern 5: In situ treatment

1.2 (professionals)

2.0 (amateurs)

7.87 (professionals)

13.20 (amateurs)

-

For use patterns 1 and 5 the PEC/PNEC values are higher than 1 indicating that there is unacceptable risk for the aquatic compartment, while this conclusion for the sediment is reached

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for all the five scenarios considered. No risk is predicted for the microorganisms in sewage treatment plant, It is suggested to restrict the in situ application of Bardap26-containing wood preservative to prevent its use on structures where direct losses to water cannot be prevented. As for other PT8 CA reports, risk mitigation measures are proposed to restrict the storage of pre-treated timber to areas of impermeable hard standing so as to prevent direct exposure of the water compartment and allow the recovery of the losses for recycling or appropriate disposal.

Moreover, due to the PEC/PNEC ratios higher than 1 for the sediment compartment, it is proposed to restrict the dipping and vacuum pressure treatment allowing it only to those plants where significant losses can be contained (e.g no drain connections to storm drains or STP) and appropriately recycled/disposed.

Terrestrial Compartment


Terrestrial compartment

Use scenario 2: Dipping process during storage 21.7 (after 30 days)

5284 (after 30 years)

Use scenario 4: Vacuum pressure process during storage 16.4 (after 30 days)

Use scenario 5: In-situ treatment 2.8 (professionals)

4.6 (amateurs)

Use scenario 6: Treated wood in service: Noise barrier 0.67

Use scenario 7: Treated wood in service: House 1.75

Use scenario 8: Treated wood in service: Transmission pole 0.45

Use scenario 9: Treated wood in service: Fence post 0.11

For the use scenarios 2, 4, 5 and 7 the PEC/PNEC values are higher than 1 suggesting that there is unacceptable for the terrestrial compartment for short and long-term use.

It is suggested to restrict the storage of the treated wood (scenarios 2 and 4) and the in situ application (scenario 5) of Bardap26-containing wood preservative to prevent its use on structures where direct losses to water cannot be prevented. It is suggested also to restrict the use treated wood in services for houses. No risk is predicted for the other use scenarios.

As for other PT8 CA reports, risk mitigation measures are proposed to restrict the storage of pre-treated timber to areas of impermeable hard standing so as to prevent direct exposure of the soil compartment and allow the recovery of the losses for recycling or appropriate disposal.

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Furthermore, it is proposed to restrict the outdoors in situ treatment with ATMAC-containing wood preservatives as direct losses to the soil compartment cannot be prevented. As for other PT8 CA reports it is proposed to give label instructions in order to prevent application to timber were direct losses to soil are possible.

It is proposed to restrict the use of treated wood for the house scenario, being the PEC/PNEC ratio higher than 1.

Environmental risk in the atmosphere

For the atmosphere compartment no PNEC values are available. However, for all use patterns, the PEC in air is considered to be negligible (≤ 1E-05) suggesting that there is no concern for this compartment.

Primary and secondary poisoning (non compartment specific effects relevant to the food chain)


Fish-eating mammals Fish-eating birds Use pattern 1: Dipping

application 0.0571 0.1016 Use pattern 2: Storage of dipping/immersed wood 0.0007 0.0012

Use pattern 3: Vacuum pressure application 0.0327 0.0583

Use pattern 4: Storage of Vacuum pressure treated wood 0.0036 0.0064

All PEC/PNEC values are < 1 for all use patterns, there is no concern with regard to non compartment specific effects relevant to the food chain (secondary poisoning via aquatic food chain).

2.2.3. List of endpoints

In order to facilitate the work of Member States in granting or reviewing authorisations, and to apply adequately the provisions of Article 5(1) of Directive 98/8/EC and the common principles laid down in Annex VI of that Directive, the most important endpoints, as identified during the evaluation process, are listed in Appendix I.

3. PROPOSAL FOR THE DECISION

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3.1. Background to the Decision

On the basis of the proposed and supported uses and the evaluation conducted as summarised in chapter 2 of this document, it can be concluded that under the conditions listed in chapter 3.2 Didecylmethylpoly(oxyethyl)ammonium Propionate (Bardap26) fulfils the requirements laid down in Article 5(1) (b), (c), and (d) of Directive 98/8/EC, apart from requirement in TNsG Chapter 2 Section 4.1. Didecylmethylpoly(oxyethyl)ammonium Propionate is proposed to be included in Annex I of the Directive provided that fully-validated analytical methods for the determination of the active substance in the active substance as manufactured and in the biocidal product are supplied by the applicant. . The Annex I – entry should, however, only include the intended uses with the conditions and restrictions proposed in this report. For the Human Health no risks have been identified for the professional users and all the use proposed can be considered acceptable. Also for the secondary exposure assessment no risks have been identified for the exposed population.

As regards the environmental risk assessment, unacceptable risks have been identified for the aquatic compartment due to the dipping, vacuum pressure and in situ applications of Bardap26-containing products.

Therefore, as for other PT8 CA reports, for in situ treatment by brush (professional or amateur), wood preservative products containing Bardap26 must not be used to treat wooden structures located where direct losses to water cannot be prevented.

It is proposed also to restrict the dipping and vacuum pressure treatment allowing it only to those plants where significant losses can be contained (e.g no drain connections to storm drains or STP) and appropriately recycled/disposed. For the terrestrial compartment unacceptable risks have been identified following storage on site and following the in situ application. For these two scenarios risk reduction measures are proposed in order to prevent the direct losses to the soil. It is proposed also to restrict the use of treated wood for the house scenario.

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3.2. Proposed Decision regarding Inclusion in Annex I

The Italian CA recommends that Didecylmethylpoly(oxyethyl)ammonium Propionate is included in Annex I to Directive 98/8/EC as an active substance for use in wood preservative products (Product-type 8), subject to the following specific provisions and risk reduction measures:

Common name: Didecylmethylpoly(oxyethyl)ammonium Propionate

IUPAC name: Not applicable

CAS No.: 94667-33-1

EC No.: None assigned

Minimum degree of purity of the active substance:

The active substance as manufactured shall have a minimum purity of 90 – 99 % w/w

Identity and maximum content of impurities:

The identity and maximum content of impurities must not differ in such a way as to invalidate the assessment for the inclusion of the active substance on to Annex I.

Specific provisions and risk reduction measures::

Member States shall ensure that authorisations are subject to the following condition:

• Wood products treated with Didecylmethylpoly(oxyethyl)ammonium Propionate must not come in contact with food or feedstuffs. Since neither analytical methods nor toxicological risk assessment for Didecylmethylpoly(oxyethyl)ammonium Propionate contamination in food and feedstuffs has been carried out, the use of Didecylmethylpoly(oxyethyl)ammonium Propionate -based wood preservative must exclude applications that may lead to contact with food and feedstuffs and contaminants thereof.

• Wood products treated with Bardap26 must not used for houses and in situ applications by brush. it is proposed to give label instructions in order to prevent application to timber were direct losses to water and soil are possible.

• The dipping and vacuum pressure treatment must be performed only by those plants where significant losses can be contained (e.g no drain connections to storm drains or STP) and appropriately recycled/disposed.

• All timber treated by dipping and vacuum pressure applications should be stored on impermeable hard standing to prevent direct losses to soil and allow losses to be collected for re-use or disposal.

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• Labels and/or safety data sheets of products authorised for industrial use should indicate that freshly timber treated by dipping application should be stored after treatment on impermeable hard standing to prevent direct losses to soil and that any losses must be collected for re-use or disposal.

• Due to the fact that for the representative wood preservative, the intended use (dipping) should be conducted with formulations which are containing the active substance in a concentration no higher than 0.7% w/w, measures for a good application should be prescribed.

• As regards occupational safety measures it suggested that suitable PPE should be worn.

3.3.. Elements to be taken into account by Member States when authorising products

• Products containing Didecylmethylpoly(oxyethyl)ammonium Propionate, may be used in the treatment of wood by Dipping/immersion process and vacuum pressure application by professional users.

• Human Health and Environmental Risk Assessment has been performed on the knowledge that the wood treatment solution employed contains 0.672% a.s. The neat concentrate of the substance (containing 8.4% a.s.) is only handled under closed conditions and so is modelled under Use Pattern 1 (see below for more details). Therefore any deviation from the value of 0.672% increasing the concentration of the substance in the final treatment solution, must undergo through a specific risk assessment.

• When authorising the product use Member States Authorities should ensure that the following specific provisions and risk reduction measures described in Sections 3.2 and 3.5 are applied.

3.4. Requirement for further information

The method submitted in Doc. IIIA 4.1(4) for determination of the pure active substance in the active substance as manufactured is considered incomplete and not correctly validated. The same analytical method has been proposed as a suitable method for the determination of the active substance in the biocidal product. The above mentioned method is considered not acceptable; besides the biocidal product also contains other component as active substance (see Annex of Confidential Data). Chapter 2, Part B, Section 4.1 of the TNsG states that in the case of a preparation containing more than one active substance, a method capable of determining each, in the presence of the other, should be provided.

3.5 Updating this Evaluation Report

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This assessment report may need to be updated periodically in order to take account of scientific developments and results from the examination of any of the information referred to in Articles 7, 10.4 and 14 of Directive 98/8/EC. Such adaptations will be examined and finalised in connection with any amendment of the conditions for the inclusion of Didecylmethylpoly(oxyethyl)ammonium Propionate in Annex I to the Directive.

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Appendix I: List of endpoints Chapter 1: Identity, Physical and Chemical Properties, Classification and

Labelling

Active substance (ISO Common Name) Not available. No EINECS/ELINCS name is available for Didecylmethylpoly(oxyethyl)ammonium propionate, either

Function (e.g. fungicide) Wood preservative

Identity (Annex IIA, point II.)

Chemical name (IUPAC) alpha.-[2-(Didecylmethylammonio)ethyl]-.omega.-hydroxy-poly(oxy-1,2-ethanediyl) propionate

Chemical name (CA) Poly(oxy-1,2-ethanediyl), .alpha.-[2-(didecylmethylammonio)ethyl]-.omega.-hydroxy-, propanoate

CAS No 94667-33-1

EC No None assigned

Other substance No. LZ1524.1 (Company code) P4140 (Company code)

Minimum purity of the active substance as manufactured (g/kg or g/l)

900 – 990 g/kg Clarification required

Identity of relevant impurities and additives (substances of concern) in the active substance as manufactured (g/kg)

None

Molecular formula C26H55NO3(C2H4O)n where n = 0−3

Molecular mass 437.777 g/mol MWs used: C=12.011; H=1.00794; N=14.0067; O=15.999 No. of oxyethyl moieties (1) MW Relative % distribution MW individual Monomer (1) 429.726 0.84 360.970 Dimer (2) 473.779 0.15 71.067 Trimer (3) 517.832 <0.01 5.178 Tetramer (4) 561.885 <0.001 0.562 MW TOTAL: 437.777

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Structural formula

n = 0-3

Physical and chemical properties (Annex IIA, point III., unless otherwise indicated)

Freezing point (state purity) No freezing point down to −50 °C (93.5% w/w)

Boiling point (state purity) 180 – 195 °C (93.5% w/w)

Temperature of decomposition None detected

Appearance (state purity) Yellow weakly aromatic liquid (93.5% w/w)

Relative density (state purity) D420 = 0.942 (93.5% w/w)

Surface tension 30.5 mN/m (1 g/L aqueous solution)

Vapour pressure (in Pa, state temperature) 1.8E−06 Pa at 20°C 4.0E−06 Pa at 25°C

Henry’s law constant (Pa m3 mol -1) 3.03E−11 Pa m3 mol-1 (monomer component) 4.72E−13 Pa m3 mol-1 (dimer component)

Solubility in water (g/l or mg/l, state temperature) Completely miscible in the pH-range from 5 to 9 at room temperature

Ethanediol: > 250 g/l at ca. 20 °C Solubility in organic solvents (in g/l or mg/l, state temperature) (Annex IIIA, point III.1)

Octanol: > 250g/l at ca. 20 °C

Stability in organic solvents used in biocidal products including relevant breakdown products (IIIA, point III.2)

Not required, since didecylmethylpoly(oxyethyl)ammonium propionate is not formulated in organic solvents other than the process solvents for biocidal products. The a.s. proved to be stable in process solvents for at least 2 years (based on storage stability of Bardap 26 and experience in use)

Partition coefficient (log POW) (state temperature) Not determined. EC methods A.8 are not applicable for surface-active substances. Assessment by KOWWIN is inaccurate (software database very limited for surfactants). log POW could be roughly obtained from solubility in pure n-octanol and water (log POW ≈ 0). However, this calculation is of no use with regard to environmental fate & behaviour and secondary poisoning risk (experimental BCF available).

Dissociation constant (not stated in Annex IIA or IIIA; additional data requirement from TNsG)

Not applicable. The a.s. is fully dissociated in water

UV/VIS absorption (max.) (if absorption > 290 nm state ε at wavelength)

No significant absorption

Quantum yield of direct phototransformation in Negligible

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water at λ > 290 nm (point VII.7.6.2.2)

Flammability Not flammable

Explosive properties Not explosive

Classification and proposed labelling (Annex IIA, point IX.)

with regard to physical/chemical data No classification with regard to toxicological data C- Corrosive

R22; R34; S1/2; S26, S28; S36/37/39; S45 with regard to fate and behaviour data No classification with regard to ecotoxicological data N- Dangerous for the environment

R50; S29; S60; S61 Specific concentration limits for the environmental classification

Cn ≥ 2.5 %: N; R50

Chapter 2: Methods of Analysis

Analytical methods for the active substance

Technical active substance (principle of method) (Annex IIA, point 4.1)

The HPLC-ELSD and GC-FID analytical methods submitted for substances different from didecylmethylpoly(oxyethyl)ammonium propionate have not be considered or commented by RMS

Screening by Ion Chromatography. Not accepted

RMS is waiting for the submission of the study report in progress specific for the active substance

Impurities in technical active substance (principle of method) (Annex IIA, point 4.1)

Screening by Ion Chromatography. Not accepted

Analytical methods for residues

Soil (principle of method and LOQ) (Annex IIA, point 4.2)

Extraction with methanol:water (90:10, v/v) containing 0.01 M ammonium formate and 0.1% formic acid. LC-MS (m/z = 356.2 for the monomer). LOQ (total didecylmethylpoly(oxyethyl)ammonium propionate) = 0.01 mg/kg

Air (principle of method and LOQ) (Annex IIA, point 4.2)

Not required. The a.s. is non-volatile and will not be used in spray application

Water (principle of method and LOQ) (Annex IIA, point 4.2)

Extraction by liquid-liquid partition with 0.01 M heptanesulfonic acid and dichloromethane. Concentration by rotary evaporation and reconstitution in 0.1 % formic acid in methanol. LC-MS (m/z = 356.2 for the monomer).

LOQ (total

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didecylmethylpoly(oxyethyl)ammonium propionate) = 0.1 µg/l

Body fluids and tissues (principle of method and LOQ) (Annex IIA, point 4.2)

Not required. The a.s. is neither toxic nor highly toxic

Food/feed of plant origin (principle of method and LOQ for methods for monitoring purposes) (Annex IIIA, point IV.1)

Not required. Wood treated with didecylmethylpoly(oxyethyl)ammonium propionate-containing biocidal product is not intended for and contains label restrictions against use in areas where food for human consumption is prepared, consumed or stored, or where the feedingstuff for livestock is prepared, consumed or stored.

Food/feed of animal origin (principle of method and LOQ for methods for monitoring purposes) (Annex IIIA, point IV.1)

Not required. Wood treated with didecylmethylpoly(oxyethyl)ammonium propionate-containing biocidal product is not intended for and contains label restrictions against use in areas where food for human consumption is prepared, consumed or stored, or where the feedingstuff for livestock is prepared, consumed or stored.


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Chapter 3: Impact on Human Health For some of the endpoints addressed in Impact on Human Health Section, tests have been conducted on the chemical and structural analog, Didecyldimethylammonium Chloride (DDAC). The justification for read across of Didecylmethylpoly(oxyethyl)ammonium Propionate with data of DDAC has been accepted.

Absorption, distribution, metabolism and excretion in mammals (Annex IIA, point 6.2)

Rate and extent of oral absorption: Based on data on DDAC, and on the highly ionic nature of the a.s., it is expected that its oral absorption is limited (around 10%) and that the majority (90%) of orally administered a.s. is excreted unabsorbed via the faeces

Rate and extent of dermal absorption: Less than 0.1% of the applied chemical and structural analog 14C-14C-DDAC dose dissolved in water fully penetrated human skin in 24h. The total dermal absorption is evaluated around 10% when the substance is diluted in water..

Distribution: Following DDAC oral administration, tissue residues were less than 1%.

Potential for accumulation: None

Metabolism Four major metabolites of DDAC were identified, as the product of alkyl chain hydroxylation.

Rate and extent of excretion: Following DDAC oral administration in rats: 89 – 99% excreted in faeces, 2.5% excreted in urine.

Toxicologically significant metabolite None

Acute toxicity (Annex IIA, point 6.1)

Rat LD50 oral 662 mg/kg bw

Rabbit LD50 dermal 3342 mg/kg bw (data on Didecyldimethylammonium Chloride)

Rat LC50 inhalation Study not conducted-not rquired

Skin irritation Corrosive

Eye irritation Corrosive

Skin sensitization (test method used and result) Buehler test – not sensitizing

Repeated dose toxicity (Annex IIA, point 6.3)

Species/ target / critical effect Any species/ g.i. mucosa/ irritation of g.i. mucosa/reduced body weight

Lowest relevant oral NOAEL / LOAEL On bardap26: NOEL = 90 mg/kg/day (rat –90 days feeding study)

Based on data on DDAC for longer studies (1 year dog):

NOELfor local effects = 3 mg/kg bw/day


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NOELfor systemic effects = 10 mg/kg bw/day

Lowest relevant dermal NOAEL / LOAEL Systemic NOAEL = 12 mg/kg bw (Data on Didecyldimethylammonium Chloride)

Lowest relevant inhalation NOAEL / LOAEL Study not conducted – not required

Genotoxicity (Annex IIA, point 6.6)

In-vitro:

In vitro gene mutation study in bacteria Ames test – negative (with and without metabolic activation)

Chromosomal aberration test – negative (with and without metabolic activation)

Mouse lymphona assay – negative(with and without metabolic activation)

In-vivo:

Cytogenetic assay - negative

Carcinogenicity (Annex IIA, point 6.4)

Species/type of tumour Rat/none, Mouse/none (Didecyldimethylammonium Chloride)

lowest dose with tumours Negative

Reproductive toxicity (Annex IIA, point 6.8)

Species/ Reproduction target / critical effect Rat/ NOAEL/ none (Didecyldimethylammonium Chloride)

Lowest relevant reproductive NOAEL / LOAEL NOAEL parental = 750 ppm

NOAEL F1 offspring = 750 ppm

NOAEL F2 offspring = 750 ppm

Species/Developmental target / critical effect Rat/ NOAEL/ none (Didecyldimethylammonium Chloride)

Lowest relevant developmental NOAEL / LOAEL NOAEL maternal = 10 mg/kg bw

NOAEL teratogen > 20 mg/kg bw

Species/Developmental target / critical effect Rabbit/ NOAEL/ none (Didecyldimethylammonium Chloride)

Lowest relevant developmental NOAEL / LOAEL NOAEL maternal = 1mg/kg bw

NOAEL teratogen = > 10 mg/kg bw

Neurotoxicity / Delayed neurotoxicity (Annex IIIA, point VI.1)


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Species/ target/critical effect Study not conducted- not required

Lowest relevant developmental NOAEL / LOAEL.

Other toxicological studies (Annex IIIA, VI/XI)

None required

Medical data (Annex IIA, point 6.9)

No specific effects have been noted.

Summary

Value Study Safety factor

Non-Professional users

ADI (if residues in food or feed)

Not applicable

Professional users AEL (Acceptable Exposure Level)

0.1 mg/kg/day (read across from DDAC)

52 week oral study in dogs 100

Reference value for dermal absorption

9.41 % (rounded to 10%) In vitro on human skin

Drinking water limit 0.1 µg/L As set by EU drinking water Directive 98/83/EC

ARfD (acute reference dose)

Not applicable

Acceptable exposure scenarios (including method of calculation)

Professional users AEL/total body dose = 1.4 – 17.7 (for indirect handling scenarios

AEL/total body dose = 4.76 – 16.67 for direct handling scenarios

Production of active substance: Not applicable

Formulation of biocidal product Not applicable

Secondary exposure Not applicable

Non-professional users Not applicable

Indirect exposure as a result of use MOS (total exposure) = 1.66E+6 – 1.82E+05 (EUSES)


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Chapter 4: Fate and Behaviour in the Environment Route and rate of degradation in water (Annex IIA, point 7.6, IIIA, point XII.2.1, 2.2)

Hydrolysis of active substance and relevant metabolites (DT50) (state pH and temperature)

pH 4: >1 year at 25°C



Photolytic / photo-oxidative degradation of active substance and resulting relevant metabolites

The photolysis data available for DDAC are adequate for Bardap26. The test substance is photolytically stable in absence of a photosensitising agent.

Readily biodegradable (yes/no) No

Biodegradation in seawater Not used in seawater

Non-extractable residues No data available

Distribution in water / sediment systems (active substance)

A biodegradation study in two water/sediment systems has been performed and shoed that the substance easily migrates from the aqueous phase to the sediment phase and is also easily adsorbed to sediments (high Koc). The degradation in the sediment phase did not increase very much after the first month and the DT50 of the total system was not reached within the 120 days test duration

Distribution in water / sediment systems (metabolites)

No data available

Route and rate of degradation in soil (Annex IIIA, point VII.4, XII.1.1, XII.1.4; Annex VI, para. 85)

Mineralization (aerobic) No data available

Laboratory studies (range or median, with number of measurements, with regression coefficient)

No data available

Field studies (state location, range or median with number of measurements)

No data available

Anaerobic degradation No data available

Soil photolysis No data available

Non-extractable residues No data available

Relevant metabolites - name and/or code, % of applied a.s. (range and maximum)

No data available

Soil accumulation and plateau concentration No data available

Adsorption/desorption (Annex IIA, point XII.7.7; Annex IIIA, point XII.1.2)

Ka , Kd Kd (Koc) values for four soil types: (DDAC) Sand: 1’095 (437’805)


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Kaoc , Kdoc

pH dependence (yes / no) (if yes type of

dependence)

Sandy loam: 8’179 (908’757) Silty clay loam: 32’791 (1’599’564) Silt loam: 30’851 (1’469’081)

Fate and behaviour in air (Annex IIIA, point VII.3, VII.5)

Direct photolysis in air Estimation of the phototransformation in air of a structural and chemical analog Didecyldimethylammonium Chloride (DDAC) indicates that the substance would be very stable in air. It is considered that the same would apply for Bardap26

Quantum yield of direct photolysis

Photo-oxidative degradation in air Latitude: ............. Season: ................. DT50 ..............

Volatilization

Monitoring data, if available (Annex VI, para. 44)

Soil (indicate location and type of study) No data available

Surface water (indicate location and type of study) No data available

Ground water (indicate location and type of study) No data available

Air (indicate location and type of study) No data available


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Chapter 5: Effects on Non-target Species

Toxicity data for aquatic species (most sensitive species of each group) (Annex IIA, point 8.2, Annex IIIA, point 10.2) Species Time-scale Endpoint Toxicity

Fish Bluegill (Lepomis macrochirus)

96 h Mortality LC50 0.52 mg/l

Zebra fish (Brachydanio rerio) 34 d Growth NOEC 0.0322 mg/l (read across from DDAC data)

Invertebrates Daphnia magna 48 h Immobilisation EC50 0.07 mg/l Daphnia magna 21 d Reproduction NOEC 0.010 mg/l

(read across from DDAC data)

Chironomus tentans 28d Mortality and growth NOEC 530 mg/kg (read across from DDAC data)

Algae Scenedesmus subspicatus 72hours Biomass production

and growth rate ErC50 0.34 mg/l

Scenedesmus subspicatus 72hours Biomass production and growth rate

NOErC 0.044 mg/l

Microorganisms Activated sewage sludge 3 hr Respiration inhibition EC50 16.8 mg/l

Effects on earthworms or other soil non-target organisms

Acute toxicity to Eisenia foetida(Annex IIIA, point XIII.3.2)

LC50 4390 mg/kg, in artificial soil NOEC 2000 mg/kg, in artificial soil

Reproductive toxicity to …………………………(Annex IIIA, point XIII.3.2)

No data available.

Acute toxicity to plants (Annex Point IIA 7.5.1.3)

EC50 mustard 283 mg/kg dw (read across from DDAC data)

Effects on soil micro-organisms (Annex IIA, point 7.4)

Nitrogen mineralization EC50 > 1000 mg/kg (read across from DDAC data)

Carbon mineralization EC50 > 1000 mg/kg (read across from DDAC data)

Effects on terrestrial vertebrates

Dose-related reduction in body weight gain - NOEC 100 mg/kg


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mammals (Annex Point IIA6.8.2) Acute toxicity to birds(Annex IIIA, point XIII.1.1)

Northern bobwhite quail LD50 = 226 mg a.s./kg bw

Dietary toxicity to birds(Annex IIIA, point XIII.1.2)

Northern bobwhite quail and mallard LC50 = >5620 mg/kg a.s. food (read across from DDAC data)

Reproductive toxicity to birds(Annex IIIA, point XIII.1.3)

Not available

Effects on honeybees (Annex IIIA, point XIII.3.1)

Acute oral toxicity Not appropriate Acute contact toxicity Not appropriate

Effects on other beneficial arthropods (Annex IIIA, point XIII.3.1)

Acute oral toxicity Not appropriate Acute contact toxicity Not appropriate Acute toxicity to …………………………………..

Not appropriate

Bioconcentration (Annex IIA, point 7.5) Bioconcentration factor (BCF) Measured BCFfish whole body = 81 (read across from DDAC

data) BCFearthworm not available

Depuration time (DT50) (DT90)

7-14d for the whole body

Level of metabolites (%) in organisms accounting for > 10 % of residues

No data available

Chapter 6: Other End Points


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Appendix II: List of Intended Uses

Summary of intended uses The biocidal product containing the active ingredient is used in two wood preservative treatment applications: dipping and vacuum pressure processes. For both application processes, the preservative is delivered to the processing plant by tanker in the form of a concentrate. The concentrate contains 8.4% of the active ingredient Didecylmethylpoly(oxyethyl)ammonium Propionate. It is diluted down to a suitable working strength with water. The degree of dilution will vary depending on the wood species, type of wood product and anticipated use. The requirements for Didecylmethylpoly(oxyethyl)ammonium Propionate in both processes vary up to 0.672%.

Organisms to be controlled Wood destroying basidiomycetes (Coniophora puteana / Coniophora spec., Coriolus versicolor, Gloephyllum trabeum, Poria vaillantii / Poria spec., Fomes spec., Trametes spec., etc.)

Wood staining molds (Aureobasidium pullulans, Sclerophoma pityopila, Ophistostoma piliferum, Aspergillus niger, Aspergillus terreus, Chaetomium globosum, Paecilomyces variotii, Penicillium funicolosum, Trichoderma viridae, etc.)

Wood boring insects (Hylotrupes bajulus, Anobium punctatum, Lyctus brunneus, termites, etc.)

Products to be protected Wood, use classes 1 to 4A according to ISO draft standard (see Document IIIA Section 2 Table 2.10.2.2.2-1)

Use concentration The use concentration depends on the type of application technique, use class required and on additional formulation components. Details see exposure-scenarios in the Risk Assessments.

Products to be protected Wood, use classes 1 to 4A according to ISO draft standard (see Document IIIA Section 2 Table 2.10.2.2.2-1)

Use concentration The use concentration depends on the type of application technique, use class required and on additional formulation components. Details see exposure-scenarios in the Risk Assessments.


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Appendix III: List of studies

Data protection is claimed by the applicant in accordance with Article 12.1(c) (i) and (ii) of Council Directive 98/8/EC for all study reports marked “Y” in the “Data Protection Claimed” column of the table below. For studies marked Yes(i) data protection is claimed under Article 12.1(c) (i), for studies marked Yes(ii) data protection is claimed under Article 12.1(c) (ii). These claims are based on information from the applicant. It is assumed that the relevant studies are not already protected in any other Member State of the European Union under existing national rules relating to biocidal products. It was however not possible to confirm the accuracy of this information.

List of studies for Active Substance (Doc. IIIA)

4.1(1) Anonymus (1990): International Standard ISO 2871-2:1990 (E). Surface active agents – Detergents – Determination of cationic-active matter content – Part 2: Cationic-active matter of low molecular mass (between 200 and 500).

6.1.5 (1) Allen, D.J (1994). P4140: Buehler delayed contact hypersensitivity study in the guinea pig. SPL project no. 102/188. Safepharm Laboratories Limited, Derby, UK (unpublished).

7.1.1.2.1 (1) Barnes, S (2004) Report No. LZA/246. Huntingdon Life Sciences, Woolley Road, Alconbury, Huntingdon. (Unpublished)

3.11 (1) Bird, L. (2004). Didecylmethylpoly(oxymethyl)ammonium Propionate Bardap 26 AS Auto ignition temperature (liquids and gases) . Report No.: LZA266/042169 Huntingdon Life Sciences, Huntingdon. (unpublished)

3.4.1 (2) Boese, and Schoenberger,B. (2001)Investigation of Dodigen 3519 with 13C-NMR spectroscopy, Project number 01/7/23-2639, Clariant Gmbh, Werk Gendorf, Germany. (unpublished)

4.2c (1) Brewin, S. (2003). Didecylmethylpoly(oxymethyl)ammonium Propionate Validation of methodology for the determination of residues in drinking, ground and surface water. Report No.: LZA245/033612 Huntingdon Life Sciences, Huntingdon.(unpublished)

4.2a (1) Brewin, S. (2003). Didecylmethylpoly(oxymethyl)ammonium Propionate Validation of methodology for the determination of residues in soil. Report No.: LZA244/033605 Huntingdon Life Sciences, Huntingdon. (unpublished)

7.1.2.1.1 (1) Bücking, H.W. and Ziemer, M. (1989) Evaluation of biodegradability of Bardap 26 (Disinfectant QAV) in the OECD-Confirmatory-Test Project No. 417/89 (B). Hoechst AG, Frankfurt (Unpublished).

7.1.1.2.1 (2) Clarke, N. (2001) Bardap 26 (LZ1524.1): Assessment of ready biodegradability; CO2 evolution test. SPL Project No. 102/381. Safepharm Laboratories Ltd, Derby, U.K. (unpublished)


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7.4.1.4 (1) Clarke, N. (2001) Bardap 26(LZ1524.1): Assessment of the inhibitory effect on the respiration of activated sewage sludge SPL Project No. 102/382 SafePharm Laboratories, Derby, U.K. (unpublished)

7.1.1.1.1 (1) Cuthbert, J. and Mullee, D. (2001) Determination of abiotic degradation, hydrolysis as a function of pH. SPL Project No. 102/383. Safepharm Laboratories Limited, Derby, UK (unpublished)

7.2.3.1 (1) Daly, D. (1989) Soil/Sediment Adsorption-Desorption of 14C-Didecyldimethylammonium Chloride (DDAC). Report No. 37009. ABC Laboratories, Inc., Columbia, MO, USA (Unpublished).

7.4.1.1 (2) Drottar K.R., Van Hoven R.L., Krueger H.O. (2001). A 96 hour flow-through acute toxicity test with the bluegill (Lepomis macrochirus). Wildlife International Ltd. Report No. 289A-154 (unpublished).

6.6.4 (1) Durward, R. (1994). P4140: Chromosome aberration teset in rat bone marrow in vivo. SPL project no. 102/187. Safepharm Laboratories Ltd., Derby, UK. (unpublished)

7.1.1.1.2 (2) Dykes, J. and M. Fennessey. (1989) Determination of the Photolysis Rate of Didecyldimethylammonium Chloride (DDAC) in pH 7 Buffered Solution at 25 °C. Report No. 37005. ABC Laboratories Inc., Columbia, MO, USA (Unpublished).

7.4.3.5.1 (1) England, D.C. and T. Leak (1995). Chronic Toxicity of Sediment-Incorporated Didecyldimethylammonium Chloride (DDAC)to Chironomus tentans. Final report No. 41005. ABC Laboratories, Columbia, MO, USA (unpublished).

7.4.3.3.1 (1) Fackler, P.H. (1990) Bioconcentration and Elimination of 14C-residues by Bluegill (Lepomis machrochirus) Exposed to Didecyldimethylammonium Chloride (DDAC). Report no. 89-7-3043. Springborn Laboratories, Inc., Wareham MA, USA (unpublished).

3.2 (1) Franke, J. (2002) Vapour Pressure Dodigen 3519 AS (Bardap 26 AS) Report No. 20010180.01. Sicherheitstechnik, Siemens Axiva, Frankfurt, Germany. (unpublished)

7.5.3.1.1 (1) Gallagher, S. and Grimes, J. and Beaver, J. (2001) Bardap 26: An acute oral toxicity study with thr northern bobwhite. Project No. 289-115 Wildlife International, Maryland, USA (unpublished)

6.4.2 Gill, M.W. and Van Miller. J.P. (1988). Ninety-day subchronic dermal toxicity study with Didecyldimethylammonium Chloride in rats. Project No: 51-554. Union Carbide, Bushy Run Research Center, R.D. 4, Mellon Road, Export, PA 15632 USA. (Unpublished)

6.5 (2) 6.7 (2)

Gill, M.W., J.S. Chun, and C.L. Wagner. (1991). Chronic dietary toxicity/oncogenicity study with Didecyldimethylammonium Chloride in rats. Report No. 53-566. Union Carbide, Bushy Run Research Center, Export, PA, U.S.A. (Unpublished)

6.7 (1) Gill, M.W., S.J. Hermansky, and C.L. Wagner. (1991). Chronic dietary oncogenicity study with Didecyldimethylammonium Chloride in mice. Report No: 53-528. Union Carbide, Bushy Run Research Center, Export, PA, U.S.A. (Unpublished)

7.5.1.3 (1) Gray, J. (2004) N,N-Didecyl-N,N-Dimethylammonium Chloride (DDAC) - Acute Toxicity to Terrestrial Plants. Huntingdon Life Sciences Report No. DKG/014 (unpublished).


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7.5.1.1 (1) H.Q.M., DeVette, R. Hanstveit and J.A. Schoonmade. (2001) The assessment of the ecological effects of Didecyldimethylammonium Chloride (Guidelines OPPTS 850.5100 Soil Microbial Community Test, OECD 216 and OECD 217 and CTB section H.4.1). Study No.: IMW-99-9048-05. TNO Chemistry, Delft, The Netherlands (unpublished).

6.1.4 (3) Hofmann, T. and Hollander, H. (1985). Hoe S 3519: Prüfung aug Augenreizung am Kaninchen. Report no. 85.1000. Hoechst Pharma Forschung Toxikologie, Frankfurt am Main, Germany (unpublished).

6.1.4 (2) Hofmann, Th. and Weigand, T. (1985). Hoe S 3519: Prűfung auf Hautreizung am Kaninchen. Report no. 85.1001. Hoechst Pharma Forschung Toxikologie, Frankfurt am Main, Germany. (unpublished).

7.4.3.4 (1) Hooftman, R.N. and H.Q.M. de Vette. (2001) Intermittent Flow Through Reproduction Test with Didecyldimethylammonium Chloride and Daphnia magna. TNO Report V99.1171. TNO Nutrition and Food Research, Department of Environmental Toxicology, The Netherlands (unpublished).

7.4.3.2 (1) Hooftman, R.N., H.Q.M. de Vette and B.Borst (2001). Early Life Stage Test under intermittent flow-thorugh conditions with Didecyldimethylammonium Chloride and the fish species, Brachydanio rerio (OECD Guideline No. 210). Report No. 99-9048-03. TNO Chemistry, Delft, The Netherlands (unpublished).

4.1 (2) Howes, D. (2004) N,N-Didecyl-N-methyl-poly(oxyethyl)ammonium Propionate – Screening by Ion Chromatography. Report No.: LZA/243. Huntingdon Life Sciences Ltd. (Unpublished)

5.3.1 Hueck, H.J.; Adema, D.M.M.; Wiegmann, J.R. (1966). Bacteriostatic, Fungistatic and Algistatic Activity of Fatty Nitrogen Compounds. Appl. Microbiol., 14(3), 308 -319 [Ref. No. A104a]

6.6.1 (1) Jung, R. and Weigand, W. (1986) Hoe S3519 Study of the mutagentic potential in strains of Salmonella typimurium (Ames test) and E.coli. Hoechst, Pharma Research Toxicology (unpublished)

3.8 Lichtenberg, F. (2000): Stability of Bardap 26 at 20°C, Lot No.1063366850. Lonza AG, Basel, Switzerland. Lonza Report No. 4027 (unpublished)

5.3.1 Linfield, W.M. (1970). Straight-Chain Alkylammonium Compounds. In "Cationic Surfactants" ed. J. Jungermann. Surfactants Science Series, Chapter 2, Marcel Dekker Inc., New York, pp. 9 – 70.

7.5.3.1.2 (1) Long, R.D., K.A. Hoxter, and G.J. Smith. (1991) Didecyldimethylammonium Chloride: A Dietary LC50 Study with the Northern Bobwhite. Report (No. 289-101). Wildlife International Ltd., Easton, MD, USA (unpublished). Lonza report No. 1785

7.5.3.1.2(2) Long, R.D., K.A. Hoxter, and G.J. Smith. (1991) Didecyldimethylammonium Chloride: A Dietary LC50 Study with the Mallard. Report (No. 289-102). Wildlife International Ltd., Easton, MD, USA (unpublished). Lonza Report No. 1783

5.7.1 McBain, A.J. (2004). Effects of quaternary-ammonium-based formulations on bacterial community dynamics and antimicrobial susceptibility. Appl. Eviron. Microbiol, 70(6), 3449-3456.

7.4.1.3 (1) Mead, C.and Mullee, D.M. (2001) Bardap 26: Algal Inhibition test. SPL Project No. 102/380 SafePharm Laboratories, Derby, U.K. (unpublished)


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6.1.1 (1) Merkel, D. (2001) Acute oral toxicity test with Bardap 26. Lab Project identification number 10502. Product Safety Labs, Dayton, USA. (unpublished)

6.1.4 (1) Merkel, D.J. (2001). Primary skin irritation test with Bardap 26. PSL project no: 10503. Product Safety Labs., New Jersey, USA (unpublished).

6.8.2 (1) Neeper-Bradley, T. L. (1991). Two-generation reproduction study in Sprague-Dawley (CD) rats with Didecyldimethylammonium Chloride administered in the diet. Report No. 52-648. Union Carbide, Bushy Run Research Center, Export, PA, U.S.A. (Unpublished)

6.8.1 (1) Neeper-Bradley, T.L. (1991). Developmental toxicity evaluation of Didecyldimethylammonium Chloride administered by gavage to CDÒ (Sprague-Dawley) rats. Project No: 53-534. Union Carbide, Bushy Run Research Center, Mellon Road, Export, PA 15632, USA. (Unpublished)

6.4.1 (2) Osheroff, M.R. (1990). Subchronic oral toxicity study of Didecyldimethylammonium Chloride in dogs. Study No. 2545-100. Hazelton Laboratories America, Inc., 9200 Leesburg Turnpike, Vienna, VA 22182, USA. (Unpublished)

3.2.1 Poncipe, C. (2006): Bardap 26. QSAR Estimation of Henry’s Law Constant. Safepharm Laboratories Ltd., Shardlow, England. Lonza Report No. 4013 (unpublished)

7.5.1.2 (1) Rodgers, M. (2003). Didecylmethylpoly(oxymethyl)ammonium Propionate (Bardap 26) Acute Toxicity (LC50) to the Earthworm. Report No.: LZA251/033986 Huntingdon Life Sciences, Huntingdon. (unpublished)

7.5.1.2 (2) Rodgers, M. 2003. Didecylmethylpoly(oxymethyl)ammonium Propionate (Bardap 26) Acute Toxicity (LC50) to the Earthworm. Report No.: LZA247/033913 Huntingdon Life Sciences, Huntingdon. (unpublished)

6.2 (1) Roper, C. S. (2001). The In Vitro Percutaneous Absorption of [14C]-Didecyldimethylammonium Chloride (DDAC) Through Human Skin. Report No. 19128. Inveresk Research. (Unpublished)

7.1.2.1.1 (2) Schaefer, E.C. (2001) Didecyldimethylammonium Chloride (DDAC): Dieaway in Activated Sludge. Project No. 289E-112. Wildlife International, Inc., Easton, MA, USA (Unpublished).

3.1.2 (1) Schneider,S.(2002) Determination of the Boiling Temperature of Bardap 26 AS/Dodigen 3519 AS. Report No. B 011/2002. AllessaChemie GmbH, Frankfurt. (unpublished)

3.1.1 (1) Schneider,S.(2002) Determination of the Freezing Temperature of Bardap 26 AS/Dodigen 3519 AS. Report No. B 010/2002. AllessaChemie GmbH, Frankfurt. (unpublished)

3.1.3 (1) Schneider,S.(2002) Determination of the Relative Density of Bardap 26 AS/Dodigen 3519 AS. Report No. B 012/2002. AllessaChemie GmbH, Frankfurt. (unpublished)

3.5 (1) Schneider,S.(2002) Determination of the Water Solubility of Bardap 26 AS/Dodigen 3519 AS. Report No. B 013/2002. AllessaChemie GmbH, Frankfurt. (unpublished)

6.5 (1) Schulze, G.E. (1991). Chronic oral toxicity study of Didecyldimethylammonium Chloride in dogs. Study No. 2545-102. Hazelton Washington, Inc., 9200 Leesburg Turnpike, Vienna, VA 22182, USA. HWA. (Unpublished)


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6.2 (2) Selim, S. (1989). Absorption, Distribution, Metabolism and Excretion Studies of Didecyldimethylammonium Chloride (DDAC) in the Rat. Study No. P01421. Biological Test Center, Irvine, CA, USA. (Unpublished)

6.1.2 (1) Siglin, J.C. (1987). Acute Dermal Toxicity Study in Rabbits LD50 Test (EPA), Test article DMD10AC. Study No. 3165.1.2C, Springborn Institute for Bioresearch, Inc., Spencerville, OH, USA. (Unpublished)

3.4.1 (1) Sloan, R. (2001) Bardap 26-Spectral data for biocidal products directive.Project No. HPT-038. Lonza Group (unpublished)

3.13(1) 3.14(2)

Sydney, P. (2006): Bardap 26 AS. Physicochemical Properties. Report No. LZA0269/062503. Huntingdon Life Sciences Ltd., Huntingdon, England. Lonza Report No. 4018 (unpublished)

6.4.1 (1) Thomas, O.N., Mullee, D.M. and Brooks, P.N. (1999). SPL project no. 102/274. Safepharm Laboratories Ltd., Derby, UK. (unpublished).

6.8.1 (2) Tyl, R.W. (1989). Developmental toxicity study of Didecyldimethylammonium Chloride administered by gavage to New Zealand white rabbits. Project No: 51-590. Union Carbide, Bushy Run Research Center, Mellon Road, Export, PA 15632, USA. (Unpublished)

7.1.1.2.2 (1) 7.4.1.4 (2)

Voelskov. (1996). Untersuchung auf Bakterienschädlichkeit Sauerstoff - Zehrungs - Hemmtest. Hoechst. Report No. V89-0273-unpublished).

7.4.1.1 (1) Wetton P.M., Mullee D.M. (2001). Acute toxicity to common carp Cyprinus carpio. SafePharm Laboratories. Report No. 102/370 (unpublished).

7.4.1.2 (1) Wetton, P.M., Mullee, D.M. (2001) Bardap 26: Acute toxicity to Daphnia Magna. SPL Project No. 102/371 SafePharm Laboratories, Derby, U.K. (unpublished)

6.6.3 (2) Wright, N.P. (2001). Bardap 26 (LZ1524.1): L5178Y TK+/- mouse lymphoma assay. SPL project no. 102/392. Safepharm Laboratories Ltd., Derby, UK. (unpublished)

6.6.2 (1) Wright, N.P. (2002). Bardap 26 (LZ1524.1): Chromosome aberration test in human lymphocytes in vitro. SPl project no. 102/391. Safepharm Laboratories Ltd., Derby, UK. (unpublished)

3.12 (1) Young, S. (2003). Didecylmethylpoly(oxyethyl)ammonium Propionate (Bardap 26 AS) Flash Point. Report No.: LZA249/033839. Huntingdon Life Sciences, Huntingdon (unpublished)

3.7 (1) Young, S. (2003). Didecylmethylpoly(oxyethyl)ammonium propionate (Bardap 26 AS) Solubility in Ethanediol and Octanol. Report No.: LZA248/033929 Huntingdon Life Sciences Ltd. Huntingdon, (unpublished)

3.14 (1) Young, S. (2004). Didecylmethylpoly(oxyethyl)ammonium Propionate (Bardap 26 AS) Viscosity. Report No.: LZA250/033939 Huntingdon Life Sciences, Huntingdon.(unpublished)

List of studies for Biocidal Product (Doc. IIIB)


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Section No Reference

3.2 (1) Warncke, U. (2004) Explosive properties of SPU-01840-F-0-SL. Document No.: Wa-030204-01840. Spiess-Urania Chemicals GmbH, Versuchsstation, Christinenthal, Germany, (unpublished). Lonza Report No. 3853

3.4 (1) 3.5 (1) 3.6 (1) 3.7 (1) 3.10.1 (1) 3.10.2 (2)

Warncke, U. (2004) Determinations of physical-chemical properties of the test item SPU-01840-F-0-SL. Study code U04PCF01. Spiess-Urania Chemicals GmbH, Versuchsstation, Christinenthal, Germany, (unpublished). Lonza Report No. 3858

3.8(2) 3.10.2(1)

Warncke,U. (2005) Determination of the viscosity and the persistent foaming of the test item Korasit KS. Spiess-Urania Chemicals GmbH, Versuchsstation Christinenthal, Germany (unpublished). Lonza Report No. 3968

5.10.2 Grinda, M.; Rudolph, D. 1994 : Efficacy test report according EN 113. BAM 81-6324 Ba. Lonza Report No. 3903

Grinda, M.; Heidrich, G. 2003 : Efficacy test report on fungus cellar testing. BAM IV.1/6771 A2. Lonza Report No. 3830

Hueck, H.J.; Adema, D.M.M.; Wiegmann, J.R. (1966). Bacteriostatic, Fungistatic and Algistatic Activity of Fatty Nitrogen Compounds. Appl. Microbiol., 14(3), 308 -319 [Ref. No. A104a]

Linfield, W.M. (1970). Straight-Chain Alkylammonium Compounds. In "Cationic Surfactants" ed. J. Jungermann. Surfactants Science Series, Chapter 2, Marcel Dekker Inc., New York, pp. 9 – 70.

Schumacher, P.; Fennert, E.M. 1995 : Efficacy test report according ENV 807. MPA 3.2/691/2. Lonza Report No. 3831

Schumacher, P.; Fennert, E.M. 1996 : Efficacy test report according EN 113. MPA 3.2/691/1. Lonza Report No. 3827

Schumacher, P.; Fennert, E.M. 1997 : Efficacy test report according EN 47. MPA 3.2/7107. Lonza Report No. 3832

5.11.2 McBain, A.J. (2004). Effects of quaternary-ammonium-based formulations on bacterial community dynamics and antimicrobial susceptibility. Appl. Eviron. Microbiol, 70(6), 3449-3456.

6.1.1 (1) Kuszewski, B. (1996). Acute Oral Toxicity Test of Korasit KS in Rats. medcon Kontraktlabor GmbH, Walsrode. Project No.: 10-04-0136/00-96. (unpublished). Lonza Report No. 3740

6.1.2 (1) Kuszewski, B. (1996) Acute Dermal Toxicity Test of Korasit KS in Rats. medcon Kontraktlabor GmbH, Walsrode. Project No.: 10-04-0135/00-96. (unpublished). Lonza Report No. 3739

6.2 (1) Leuschner, P. J. (2003). Acute Skin Irritation Test (Patch Test) of SPU-01840-F-O-SL in Rabbits. Laboratory of Pharmacology and Toxicology KG, Hamburg. LPT Report No.: 16754/03 (unpublished). Lonza Report No. 3738


ammonium Propionate



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6.2 (2) Leuschner, J. (2003). Acute Eye Irritation Study of SPU-01840-F-O-SL by instillation into the conjunctival sac of Rabbits. Laboratory of Pharmacology and Toxicology KG, Hamburg. LPT Report No.: 16755/03 (unpublished). Lonza Report No. 3737

6.3 (1) Chevalier, F. (2003). Examination of SPU-01840-F-O-SL in the Skin Sensitisation Test in Guinea Pigs according to Magnusson and Kligman (Maximisation Test). Laboratory of Pharmacology and Toxicology KG, Hamburg. LPT Report No.: 16756/03 (unpublished). Lonza Report No. 3736

7.4 (1) Scheerbaum, D. (2004) Acute Toxicity of SPU-01840-F-0-SL to Fish. Dr. U. Noack- Laboratorium für Angewandte Biologie. Project No. 030505SU (unpublished). Lonza Report No. 3861

7.4 (2) Noack, U. (2004) Acute Toxicity of SPU-01840-F-0-SL to Daphnia magna. Dr. U. Noack- Laboratorium für Angewandte Biologie. Project No. 030505SU (unpublished). Lonza Report No. 3862

7.4 (3) Scheerbaum, D. (2004) Acute Toxicity of SPU-01840-F-0-SL to Algae. Dr. U. Noack- Laboratorium für Angewandte Biologie. Project No. 030505SU (unpublished). Lonza Report No. 3863