Directorate-General forEnvironment
Green Economy
Chemicals
Directorate-General for Internal Market, Industry, Entrepreneurship and SME's
Consumer, Environmental and Health Technologies
REACH
Chemicals
Brussels, 13 July 2016
Doc.CA/57/2016
21st Meeting of Competent Authorities for REACH and CLP (CARACAL)
29 June – 1 July 2016
Open session
Room: 1D, Centre Albert Borschette
Rue Froissart 36
1040 Brussels, Belgium
Concerns: Applicability of the additivity approachto any human health hazardclass
Agenda Point:7 (CLP)
Action Requested:Written comments on this document should be sent by15 August 2016 to and
Subject: Applicability of the additivity approach to any human health hazard class
1. The subject matter
Definition of the additivity approach:
In general, additivity means the approach to classification of mixtures when data are available on the components, but not on the mixture as a whole. According to the additivity theory each hazardous component present in the mixture contributes to the overall hazardous properties of the mixture in proportion to its potency and concentration (Section 3.2.3.3.2 of Annex I to Regulation 1272/2008 (skin irritation)).
Article 11 of Regulation 1272/2008 (CLP) defines the thresholds (cut-off values) above which the presence of a substance needs to be taken into account for the purposes of classification of a substance or a mixture containing that hazardous substance, whether as an identified impurity, additive, or individual constituent. The cut-off value shall be determined as set out in section 1.1.2.2 of Annex I. Some cut-off values are also provided in table 1.1 of Annex I.
The additivity approach (or summation method) is explicitly mentioned in some sections of part 3 (in particular sections 3.1., 3.2 and 3.3) and part 4 of Annex I of CLP. In this Annex I, the additivity method is explicitly mentioned in relation to the following hazard classes: acute toxicity (section 3.1.3.6), irritancy (sections 3.2.3.3.2 (skin irritation) and 3.3.3.3.2 (eye irritation)) and environmental hazard classification (section 4.1.3.2).
The main issue is whether the additivity approach is also applicable to other health hazards even if Annex I CLP does not explicitly mention this method for them.
2. Background
At the CARACAL meeting on 9 March 2016, the Commission services in charge of CLP have committed to consult the Legal Service of the Commission on the interpretation of Article 12(c) of the CLP Regulation on the possibility to apply the additivity approach to any human health hazard classes. This issue was more specifically raised for anti-coagulant rodenticides that could contain several active substances classified as toxic for reproduction (see Annex 1: document from France presented at the meeting of 9 March 2016).
3. Conclusion
It is clear that the additivity approach applies to the hazard classes for which additivity is explicitly mentioned in one of the sections related to specific hazard classes in Annex I. These hazard classes are listed in table 1.1 of Annex I that contains the generic cut-off values to be taken into account in accordance with Article 11 of the CLP.
For other health hazards, the classification method mentioned explicitly for each of these hazards in Annex I of the CLP should be used, based on Article 13 and Annex I to the CLP. In this context, the additivity approach also plays a role based on the combination of two elements which need to be taken into account for the classification of certain mixtures and that are equally applicable to substances.
Firstly, Article 12(c) of the CLP requires scientific evidence to be taken into account when it demonstrates the potential occurrence of synergistic or antagonistic effects among the substances in a mixture for which the evaluation was decided on the basis of the information for the substances in the mixture. Secondly, according to Section 1.1.1 of Annex I to the CLP the weight of evidence approach and expert judgment should be followed to determine the classification of a substance or a mixture, in particular where the classification criteria cannot be applied directly. The additivity approach is a well-established practice for the classification of substances and brings together the necessary consideration of the combined effects of constituents as well as weight of evidence approach and expert judgement. Therefore, it could be usefully applied under Article 12(c) and Section 1.1.1 of Annex I for all hazard classes if justified by a scientific point of view as for example because the effects of substances to be added are the same or very similar, as in the case of the anti-coagulant rodenticides listed in the document presented by France.
Annex – Document related to the use of additivity for the classification of rodenticides as toxic for reproduction, presented by the French Competent authorities (CA) at the CARACAL meeting on 9th of March 2016.
Additivity of concentration for the reprotoxic classification
This paper presents a general agreement among French CAs and Helpdesks for biocides and CLP, and ECHA Helpdesk.
By this paper, French ACs would like to know the views of the Commission and the MS to be sure that the EU level ensuring the same rule to be applied around Europe when a classification is required based on an expert judgement approach.
If such interpretation below is considered not completely clear, a clarification may be added in the EU guidance documents, or it might lead to address some issues in the GHS Sub-Committee to clarifying the aim and the applicability of some classification criteria.
The case (highlighted in the context of the Biocide regulation)
Reprotoxic category 1 shall soon apply for 8 substances of the AVK family (Anti-Vitamin K, anticoagulant rodenticides active substances[1]).
Based on RAC methodology, specific concentration limits (SCL) for reprotoxic category 1 substances is established at 0.003%. That means that when rodenticide products will contain more than 0.003% of an AVK substance, the product itself will be classified in the same way.
Most of the rodenticides products currently contain 0.005% AVK. Some biocide formulators are currently testing less-concentrated substances to formulate new products with two AVK substances which are both reprotoxic category 1, with individual concentrations below the SCL (for instance each concentration being 0.0025%, both substances are < the SCL of 0.003% but we have indeed a total of 0.005% of reprotoxic AVKs in the product).
A French manufacturer recently questioned CLP ECHA Helpdesk and Biocide French Helpdesk on this topic in the sense that : shall we classify the product as reprotoxic or not ?
French Biocide and CLP ACs share ECHA Helpdesk position
The additivity of the substances concentrations have to be taken into account for the classification of the product.
Here below is the justification given by ECHA, with which French ACs fully agrees, stating that not taking into account the obvious additivity of two substances with same mode of action to avoid classification of a mixture would not be in line with the intention of Article 12(c) of CLP :
“The legal text is based on the assumption that toxicity to reproduction is normally not additive. There are many mechanisms for toxicity to reproduction and these may not be additive. However, it would, as you say, be hard to justify scientifically this approach to the AVK rodenticides, which clearly have the same Mode of Action.
And indeed, in Article 12(c) CLPR, it is stated that “Where, as a result of the evaluation carried out pursuant to Article 9, the following properties or effects are identified, manufacturers, importers and downstream users shall take them into account for the purposes of classification: … (c) adequate and reliable scientific information demonstrates the potential occurrence of synergistic or antagonistic effects among the substances in a mixture for which the evaluation was decided on the basis of the information for the substances in the mixture”. Therefore, interactions between components of a mixture need to be taken into account, whether additivity applies to the hazard class or not. Although “synergy” is generally defined as an effect greater than the sum of the individual effects of the components, it is not defined in the legal text. Thus, to avoid classification of a mixture of two AVKs would not be in line with the intention of Article 12(c). “
More details on the rational supported by the FR ACs :
- Articles 5 and 6 of the CLP Regulation on the identification and examination of available information refer to the tests but also to any available information, such as read-across (Annex XI of the REACH Regulation).
- It is clearly established that for reproductive effects, the substances are considered as a group of substances with the same mode of action: the classification is based on the same data by read-across of a third substance (warfarine). This is stated in the RAC’s opinion. Do not take this information into account here would be to not use all the available information.
- The appropriate technical approach to classify a mixture with such data would be the expert judgment as stated in CLP’s annex I § 1.1.1.2 and § 1.1.1.3:
“ 1.1.1.2. The approach to classifying mixtures may include the application of expert judgement in a number of areas in order to ensure existing information can be used for as many mixtures as possible in order to provide protection for human health and the environment. Expert judgement may also be required in interpreting data for hazard classification of substances, especially where weight of evidence determinations are needed.
1.1.1.3. A weight of evidence determination means that all available information bearing on the determination of hazard is considered together, such as the results of suitable in vitro tests, relevant animal data, information from the application of the category approach (grouping, read-across), (Q)SAR results, human experience such as occupational data and data from accident databases, epidemiological and clinical studies and well documented case reports and observations. The quality and consistency of the data shall be given appropriate weight. Information on substances or mixtures related to the substance or mixture being classified shall be considered as appropriate, as well as site of action and mechanism or mode of action study results. Both positive and negative results shall be assembled together in a single weight of evidence determination.”
1
[1]In the RAC opinions adopted March 2014, warfarine and brodifacoum are proposed as Repr. 1A whereas bromadiolone, chlorophacinone, coumatetralyl, difenacoum, difethialone, flocoumafen are proposed as Repr. 1B.