Rapporteur Member State: Italy / Quaternary ammonium compounds, benzyl-C12-16-alkyldimethyl, chlorides / September 2011 /
Directive 98/8/EC concerning the placing biocidal products on the market
Inclusion of active substances in Annex I to Directive 98/8/EC
Assessment Report
Quaternary ammonium compounds, benzyl-C12-16-alkyldimethyl, chlorides
Product-type 8
(Wood preservative)
date SCB
Annex I –Italy
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Quaternary ammonium compounds, benzyl-C12-16-alkyldimethyl, chlorides / Product-type 8 / date SCB /Quaternary ammonium compounds, benzyl-C12-16-alkyldimethyl, chlorides (PT 8)
Finalised in the Standing Committee on Biocidal Products at its meeting on date SCB in view of its inclusion in Annex I to Directive 98/8/EC
CONTENTS
1. STATEMENT OF SUBJECT MATTER AND PURPOSE 4
1.1. Procedure followed 4
1.2. Purpose of the assessment report 5
1.3. Overall conclusion in the context of Directive 98/8/EC 6
2. OVERALL SUMMARY AND CONCLUSIONS 7
2.1. Presentation of the Active Substance 7
2.1.1. Identity, Physico-Chemical Properties & Methods of Analysis 7
2.1.2. Intended Uses and Efficacy 12
2.1.3. Classification and Labelling 14
2.2. Summary of the Risk Assessment 16
2.2.1. Human Health Risk Assessment 16
2.2.1.1 Hazard identification 16
2.2.1.2 Effects assessment 17
2.2.1.3 Exposure assessment 18
2.2.1.4 Risk characterization for local effects 26
2.2.2 Environmental Risk Assessment 36
2.2.2.1 Fate and distribution in the environment 36
2.2.2.2 Effects assessment 38
2.2.2.3 PBT assessment 40
2.2.2.4 Exposure assessment 41
2.2.2.5 Risk characterisation 44
3. DECISION 49
3.1. Background to the Proposed Decision 49
3.2. Proposed Decision regarding Inclusion in Annex I 50
3.3. Elements to be taken into account by Member States when authorising products 52
3.4. Requirement for further information 52
3.5. Recommended Measures 53
3.6. Updating this Assessment Report 53
Appendix I: List of end points 54
Chapter 1: Identity, Physical and Chemical Properties, Details of Uses, Further Information, and Proposed Classification and Labelling 54
Chapter 2: Methods of Analysis 57
Chapter 3: Impact on Human Health 58
Chapter 4: Fate and Behaviour in the Environment 64
Chapter 5: Effects on Non-target Species 66
Chapter 6: Other End Points 68
Appendix II: List of Uses Supported by Available Data 69
Appendix III: List of Studies 70
1. STATEMENT OF SUBJECT MATTER AND PURPOSE
1.1. Procedure followed
This assessment report has been established as a result of the evaluation of Quaternary ammonium compounds, benzyl-C12-16-alkyldimethyl, chlorides as product-type 8 (wood preservative), carried out in the context of the work programme for the review of existing active substances provided for in Article 16(2) of Directive 98/8/EC concerning the placing of biocidal products on the market[1], with a view to the possible inclusion of this substance into Annex I or IA to the Directive.
Quaternary ammonium compounds, benzyl-C12-16-alkyldimethyl, chlorides (CAS no. 68424-85-1) was notified as an existing active substance, by Lonza Cologne GmbH, Stepan Europe, Mason Europe Limited, hereafter referred to as the applicant, in product-type 8.
Commission Regulation (EC) No 2032/2003 of 4 November 2003[2] lays down the detailed rules for the evaluation of dossiers and for the decision-making process in order to include or not an existing active substance into Annex I or IA to the Directive.
In accordance with the provisions of Article 5(2) of that Regulation, Italy was designated as Rapporteur Member State to carry out the assessment on the basis of the dossier submitted by the applicant. The deadline for submission of a complete dossier for Quaternary ammonium compounds, benzyl-C12-16-alkyldimethyl, chlorides as an active substance in Product Type 8 was 28th March 2004, in accordance with Annex V of Regulation (EC) No 2032/2003.
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 and the evaluation taken up again on 27th March 2006 after the applicant has submitted the necessary data. After that, the evaluation phase was suspended again on the 17th July 2006 and taken up on 18th July 2007.
On 31st July 2007, the Rapporteur Member State submitted, in accordance with the provisions of Article 10(5) and (7) of Regulation (EC) No 2032/2003, to the Commission and the applicant a copy of the evaluation report, hereafter referred to as the competent authority report. The Commission made the report available to all Member States by electronic means on 19th September 2007. The competent authority report included a recommendation for the inclusion of Quaternary ammonium compounds, benzyl-C12-16-alkyldimethyl, chlorides in Annex I to the Directive for PT 8.
In accordance with Article 12 of Regulation (EC) No 2032/2003, the Commission made the competent authority report publicly available by electronic means on 10th October 2007. This report did not include such information that was to be treated as confidential in accordance with Article 19 of Directive 98/8/EC.
In order to review the competent authority report and the comments received on it, consultations of technical experts from all Member States (peer review) were organised by the Commission. Revisions agreed upon were presented at technical and competent authority meetings and the competent authority report was amended accordingly.
On the basis of the final competent authority report, the Commission proposed the inclusion of Quaternary ammonium compounds, benzyl-C12-16-alkyldimethyl, chlorides in Annex I to Directive 98/8/EC and consulted the Standing Committee on Biocidal Product on [date].
In accordance with Article 11(4) of Regulation (EC) No 2032/2003, the present assessment report contains the conclusions of the Standing Committee on Biocidal Products, as finalised during its meeting held on [date].
1.2. Purpose of the assessment report
This assessment report has been developed and finalised in support of the decision to include Quaternary ammonium compounds, benzyl-C12-16-alkyldimethyl, chlorides in AnnexI to Directive 98/8/EC for product-type 8. The aim of the assessment report is to facilitate the authorisation in Member States of individual biocidal products in product-type 8 that contain Quaternary ammonium compounds, benzyl-C12-16-alkyldimethyl, chlorides . In their evaluation, Member States shall apply the provisions of Directive 98/8/EC, in particular the provisions of Article 5 as well as the common principles laid down in Annex VI.
For the implementation of the common principles of Annex VI, the content and conclusions of this assessment report, which is available at the Commission website[3], shall be taken into account.
However, where conclusions of this assessment report are based on data protected under the provisions of Directive 98/8/EC, such conclusions may not be used to the benefit of another applicant, unless access to these data has been granted.
1.3. Overall conclusion in the context of Directive 98/8/EC
The overall conclusion from the evaluation is that it may be expected that there are products containing Quaternary ammonium compounds, benzyl-C12-16-alkyldimethyl, chlorides for the product-type 8, which will fulfil the requirements laid down in Article 10(1) and (2) of Directive 98/8/EC. This conclusion is however subject to:
i. compliance with the particular requirements in the following sections of this assessment report,
ii. the implementation of the provisions of Article 5(1) of Directive 98/8/EC, and
iii. the common principles laid down in Annex VI to Directive 98/8/EC.
Furthermore, these conclusions were reached within the framework of the uses that were proposed and supported by the applicant (see Appendix II). Extension of the use pattern beyond those described will require an evaluation at product authorisation level in order to establish whether the proposed extensions of use will satisfy the requirements of Article 5(1) and of the common principles laid down in Annex VI to Directive 98/8/EC.
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Quaternary ammonium compounds, benzyl-C12-16-alkyldimethyl, chlorides / Product-type 8 / date SCB /2. OVERALL SUMMARY AND CONCLUSIONS
2.1. Presentation of the Active Substance
2.1.1. Identity, Physico-Chemical Properties & Methods of Analysis
Identification of the active substance
CAS No. / 68424-85-1EINECS No. / 270-325-2
Other substance No.: / None assigned
IUPAC Name / Not applicable
Common name, synonyms / Quaternary ammonium compounds, benzyl-C12-16-alkyldimethyl, chlorides;
ADBAC
Alkylbenzyldimethylammonium Chloride
Alkyl(C12-16)dimethylbenzylammonium chlorides
Ammonium, alkyl(C12-C16)dimethylbenzyl-, chlorides
Benzyl-C12-C16-alkyldimethyl ammonium chlorides
Chemical name (CA) / Quaternary ammonium compounds, benzyl-C12-16-alkyldimethyl, chlorides
Molecular formula / C9 H13 N Cl R where R = C12 H25, C14 H29 or C16 H33
Structural formula /
Alkylchainlengths distribution / Chain
Length / Specification for
68424-85-1(§) / Typical Analysis of a Commercial Product
C12 / 39 - 75% / 41.82%
C14 / 20 - 52% / 48.43%
C16 / 12% / 9.51%
Molecular weight (g/mol) / 340.0 – 396.1 g/mol (Avg. = 359.6 g/mol)
Purity / 94 - 99% w/w dry weight (*)
Impurities / See Confidential Data
The active substance Quaternary ammonium compounds, benzyl-C12-16-alkyldimethyl, chlorides (C12-16-ADBAC) does not contain additives or impurities that would be of toxicological/environmental concern.
(§) In May 2011 the RMS agreed with the amendment proposed by the joint Notifiers as regards the alkyl chain lengths distribution of the active substance. This amendment, reflecting the complexity of the raw materials and processes used in their manufacture, can be considered as a negligible change, which does not affect the overall assessment of the active substance for both human and environmental health that has been conducted so far.
(*) The active substance is not manufactured solvent-free but always exists in process solvents.
Identification of the representative product
Trade name / BQ-25Manufacturers development code number / Not assigned
Active substance / Quaternary ammonium compounds, benzyl-C12-16-alkyldimethyl, chlorides
Content of the active substance / 25% (a.s. 94 - 99%)
Function / Fungistatic, insecticide
Physical state of preparation / Liquid
Nature of preparation / Solution
The product does not contain substances of concern.
Physico-chemical properties
The active substance Quaternary ammonium compounds, benzyl-C12-16-alkyldimethyl, chlorides (C12-16-ADBAC) is a light beige solid which decomposes above 150°C before melting. Its relative density was determined to be 0.96 at 20°C.
Its vapour pressure was calculated to be 6.03E-04 Pa at 20°C, 8.5E-04 at 25°C and 4.22E-03 at 50°C, with a Henry’s Law constant of 5.03E-07 Pa m3 mol –1 at 20°C.
C12-16-ADBAC is highly soluble in water (water solubility at 20°C is 409 g/l at pH 5.5; 431 g/l at pH 6.5; 379 g/l at pH 8.2). Furthermore, it is readily soluble in Ethanol (>250 g/l at 20°C), Isopropanol (>250 g/l at 20°C) and Octanol (>250 m/l at 20°C).
The partition coefficient n-octanol/water is not determinable since the active substance is a surfactant in the octanol/water system, thus preventing the use of the shake-flask method. The HPLC Method is not applicable either, due to the absence of suitable calibration compounds and to the fact that ionic compounds interact with the HPLC column by forces other than partitioning. Also the log Pow assessment by KOWWIN is deemed inaccurate, being the software database very limited for surface active substances. On the other hand, log Pow could be roughly obtained from solubility in n-octanol and water (Pow » 1, log Pow » 0). However, this result is of no use with regard to environmental fate and behaviour and secondary poisoning risk assessment, since there is an experimental BCF available.
C12-16-ADBAC does not exhibit hazardous physico-chemical properties. The substance is thermally stable, is not classified as highly flammable and does not show explosive or oxidising properties. C12-16-ADBAC has a low vapour pressure and is highly soluble in water. There is no risk to be expected due to the physico-chemical properties of the product BQ-25, either.
Analytical methods
Analysis of the active substance as manufactured
The Applicant proposed a method in which the quaternary ammonium content was determined using a biphasic competitive titration between reagent water and chloroform with bromophenol blue indicator. The titrant, sodium tetraphenylborate (STPB), was standardized before being used to titrate triplicate 1:1:1 solutions of 5 mg/ml aqueous ADBAC Quat 80%, pH 10 phosphate buffer and chloroform containing indicator. Gas chromatography with flame ionization detection (GC-FID) was used to determine the distribution of the alkyl chain lengths of Alkyl Dimethyl Benzyl Ammonium Chloride. The test substance was diluted in isopropanol to yield solutions of 126 and 123 mg/ml which were injected (1ml) onto the GC. Following peak assignment relative to reference chromatograms, the alkyl chain lengths distribution was calculated assuming relative response coefficients of unity for duplicate analyses.
The requirements stated in TNsG Chapter 2 Section 4.1 were not accomplished. No data concerning recovery rates, linearity, limit of determination, specificity and intra-laboratory repeatability were available. A suitable method was requested.
An additional analytical method (“Kurz M. and Ranft V. (2007) “Determination of quaternary ammonium compounds and related quaternary impurities by HPLC-ELSD”, Section 4.1(2) Doc. IIIA) was submitted at the mid-July 2007. The method was not deemed acceptable, due to the deficiencies/mistakes affecting both the validation work and the original study report. Hence, the RMS required the full validation of the developed method for both C12-16-ADBAC and impurities > 0.1% w/w, in compliance with SANCO/3030/99 rev.4 11/07/00. Anyway, at the TMIV08 it was concluded that the HPLC-ELSD method could be considered acceptable for C12-16-ADBAC. It was also agreed that the Applicant should have provided further information on the analytical method and considered the possibility to use of an internal standard for quantitative analysis as suggested by AT.
In 2011, a new study (Zehr, P.S. (2010), “Methods Validation for the Preliminary Characterization Analyses of Alkyldimethyl[ethyl]benzyl Ammonium Biocides”) for the determination of the active substance C12-16-ADBAC, impurities and process solvents in commercially available technical concentrate Maquat MC1412-50% (nominal active substance content: 50% w/w) was submitted, superseding Doc.IIIA Sections 4.1(1) and (2). Results are now summarized in Section4.1(3)(a) in Doc.IIIA and Section 4.1(3)(b)-(c) in the Confidential Data. Except for one impurity, valid analytical methods are available for impurities and process solvents in 50% w/w C12-16-ADBAC-based technical concentrate; additional information/clarification must be provided in any case (please refer to the RMS comments/requests in the evaluation box of the relevant study summaries).
Following the submission of Zehr, P.S. (2010), in April 2011 an additional study addressing batch-analysis (Dung Truong, M.S. (2011), “Batch analysis of Alkyl(C12-16)dimethylbenzyl Ammonium Chlorides”) was presented. Only two batches per Notifier have been investigated, whereas the TNsG for on the assessment of technical equivalence of substances regulated under 98/8/EC require the analytical profile of at least five different representative batches of each source for the purpose of Tier I assessment. In conclusion, a new five-batch analysis for each source of the active substance must be submitted to allow the assessment of the technical equivalence of the three joint Notifiers supporting C12-16-ADBAC and also to confirm the active substance specification under Sec. 2 Doc.IIIA. Data should be submitted to the RMS prior to product authorization phase at national level.