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BIOCIDES: BIP 6.7 - Scoping document for the drafting of guidance for cumulative and synergistic effectsDraft: 10 May 2012
Tobias Porsbring
Annankatu 18, P.O. Box 400, FI-00121 Helsinki, Finland | Tel. +358 9 686180 | Fax +358 9 68618210 | echa.europa.eu
CA-July12-Doc.5.2.h
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Annankatu 18, P.O. Box 400, FI-00121 Helsinki, Finland | Tel. +358 9 686180 | Fax +358 9 68618210 | echa.europa.eu
CA-July12-Doc.5.2.h
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Table of contents
1. Introduction...3
2. Scope, approach and definitions...3
3. Legal provisions...4
4. Prospects...6
In depth analysis
Annex I Approach and scope...8
Annex II Mixture toxicity assessment in product authorisations...10
Annex III Cumulative exposure assessment...17
Annex IV BPR and beyond - the challenges of real world mixtures...20
1. Introduction
The biocides regulation 2009/0076 (COD) (BPR), which will replace the current biocides directive 98/8/EC (BPD), will apply from 1 September 2013. From this date the provisions of the BPR will apply also to biocides evaluated under the BPD. For the implementation of the BPR, a number of guidance documents are required, as set down in the legal text of the BPR. This concept paper concerns the drafting of guidance for cumulative and synergistic effects. The BPR states that the (eco)toxicological risk assessment of the active substance as well as the biocidal product is to take into account cumulative and synergistic effects (Article 19(2)). It also states that the European Chemicals Agency is to, in collaboration with the Commission, member states and interested parties, develop and provide further guidance on the scientific definitions and methodologies for the assessment of cumulative and synergistic effects (recital 15 of Annex VI). The first section of this scoping document provides a summary of the proposed scope, approach, and prospects for guidance. A more comprehensive analysis can be found in the Annexes to this scoping document.
2. Scope, Approach and Definitions
ECHA proposes to split the work on guidance for cumulative and synergistic effects into four different work packages (Table 1). The bases for the proposal are the extensive scientific and regulatory scope of the issue, considering further that different areas are in different stages of scientific and technical progress (see below and in the Annex to this concept paper for further details). Accordingly, the proposed division would facilitate that guidance on already well advanced topics can be finalised and published as soon as possible. For all projects, the regulatory scope of the guidance is active substances and products with uses that will be regulated under the BPR.
ENVIRONMENT / HUMAN HEALTHE1. Mixture toxicity assessment (product authorisations) / H1. Mixture toxicity assessment (product authorisations)
E2. Cumulative exposure assessment / H2. Cumulative exposure assessment
Table 1. Proposed distinction and numbering of guidance work packages for "synergistic effects" ("mixture toxicity") and cumulative effects ("cumulative exposure").
The regulatory, chemical, and spatiotemporal scope of the guidance to be produced is according to the following proposed definitions of cumulative and synergistic effects. These definitions are proposed on the basis of the provisions set down in the BPR, also taking into account the current state of scientific and regulatory progress. As such, they are not immediately applicable to regulatory frameworks other than BPR and BPD. As proposed here the definitions should be seen as applicable for guidance development for both, human health[1] and environmental risk assessments.
Synergistic effects - Will in the following be referred to as mixture toxicity (product authorisations). This refers to the risk to human health and environment from those environmental, occupational and residential mixture(s), which are formed by the relevant substances in a biocidal product, including degradation products, during the use, service life or waste phase of the product.
Cumulative effects - Will in the following be referred to as cumulative exposure. Cumulative exposure is the overall exposure to the same biocidal active substance by emissions during the use, service life or waste phase of different products belonging to the same PT or different PTs (Groß et al 2011). This does not include the potential additional exposure from the same substance resulting from non-biocidal uses regulated under different legal frameworks.
3. Legal provisions
The BPR sets down the following provisions for the consideration of cumulative exposure and mixture toxicity under the evaluation of an active substance, and the authorisation of biocidal products, respectively:
Article 4(1) "An active substance shall be approved ... if at least one biocidal product containing that active substance may be expected to meet the criteria laid down in point (b) of Article 19(1) taking into account the factors set out in Article19(2) and(5). ..."
Article 19(1) (b) "it is established, according to the common principles for the evaluation of dossiers for biocidal products laid down in Annex IV, that the biocidal product, when used as authorised and having regard to the factors referred to in paragraph 2 of this Article, fulfils the following criteria:
...
(iii) the biocidal product has no immediate or delayed unacceptable effects itself, or as a result of its residues, on human and animal health ...
(iv) the biocidal product has no unacceptable effects itself, or as a result of it residues, on the environment ..."
Article 19(2) "The evaluation of whether a biocidal product fulfils the criteria set out in point(b) of paragraph1 shall take into account the following factors:
...
(d) cumulative effects
(e) synergistic effects"
Annex VI recital 3. "In order to ensure a high and harmonised level of protection of human and animal health and of the environment, any risks arising from the use of a biocidal product shall be identified. To achieve this, a risk assessment shall be carried out to determine the acceptability or otherwise of any risks that are identified. This is done by carrying out an assessment of the risks associated with the relevant individual components of the biocidal product taking into account any cumulative and synergistic effects."
Annex VI recital 15. "In carrying out the assessment, the possibility of cumulative and synergistic effects shall also be taken into account. The Agency shall, in collaboration with the Commission, Member States and interested parties, develop and provide further guidance on the scientific definitions and methodologies for the assessment of cumulative and synergistic effects."
Additionally, Article 8(3) opens up the possibility for member states to consider also risks resulting from the cumulative exposure to different biocidal active substances:
Article 8(3) "Where the evaluating competent authority considers that there are concerns for human health or the environment as a result of the cumulative effects from the use of biocidal products containing the same or different active substances, it shall document its concerns in accordance with the requirements of the relevant parts of Section II.3 of Annex XV to Regulation (EC) No 1907/2006 and include this as part of its conclusions."
It is the opinion of ECHA that the guidance requested in Annex VI recital 15 should not cover combination effects resulting from cumulative exposure to multiple actives (Article 8(3)), as this represents a significant step towards real world exposure situations, i.e. complex mixtures made up from chemicals regulated under several different legal frameworks. Integrated risk assessment approaches including cross-regulatory efforts would be better suited to address risks from such mixtures. In any case, we note that chemical mixtures are of a high political priority, as pointed out e.g. by The Council of the European Union[2], and more recently by the Nordic Council of Ministers in the report "Chemical cocktails - a serious matter of concern" [3] as well as the OECD in the report "Environmental outlook to 2050: The consequences of inaction - Key findings on health and environment" [4]. Accordingly, and acknowledging also the increased scope of Article 8(3), ECHA would welcome and contribute to an EU-wide horizontal effort to assess and manage real world mixtures.
4. Prospects
This section provides a brief overview on the state of the art and prospects for guidance development according to the different proposed work packages (Table 1).
E1. Mixture toxicity assessment (product authorisations), Environment. The results of a research project funded by the German federal environment agency (UBA) on mixture toxicity from biocides, also incorporating a proposed approach for product authorisations, was discussed at a workshop at the UFZ, Leipzig, in April 2012. Although the project focussed on the provisions of the current biocides directive, it is directly applicable also to the BPR. As such, the workshop constituted the first concrete step towards guidance for the purpose of the BPR. A follow-up workshop is planned for the technical meeting (TM) III 2012 (October). It is likely that guidance will be available before the BPR application date. Even taking into account subsequent discussions at TM-level and considering also subsequent adoption at Competent Authority meeting level. The guidance should set down principles and a tiered approach to the estimation of joint risks from the relevant substances in a biocidal product, for the purpose of biocidal product authorisations.
H1. Mixture toxicity assessment (product authorisations), Human health. It is likely that guidance will be available before or shortly after the BPR application date. France aims to have a re-drafted proposal available July 2012 latest. Taking into account member states´ previous comments and discussions it should represent an accordant approach and should be scheduled for continued TM discussions in 2012. As for E1, the aim is to set down principles and a tiered approach for the consideration of mixture toxicity in the human health risk assessment in biocidal product authorisations.
E2. Cumulative exposure assessment, Environment. A comprehensive report on the issue (Groß et al 2011) was recently published on the website of the German federal environment agency. The report was presented at TM I, 2012. For TM I 2012, there were also discussions on a cumulative exposure assessment for the different uses of one substance in PT6 (In-can preservatives). However, no previous guidance exists, and experience is lacking. For many PTs or specific uses, exposure scenarios are not even available. As the different exposure scenarios have been developed with a single use in mind, a crucial issue is their usability for cumulative exposure assessments. Accordingly, the exact deliverable(s) under E2 remains to be defined in collaboration with the Commission and member states. In any case, guidance for cumulative exposure assessments incorporating all PTs or even different uses within one PT will not be available before the BPR application date. Such guidance would have to be delivered step-wise as experience is accumulated and according to the progress of the BPD review program and product authorisations.
A concrete step forward would be to provide general principles and criteria for triggering an assessment. Aim of a current research project of the German UBA is to develop a harmonised technical guidance document on cumulative environmental risk assessment. The project is executed by Öko-Institut e.V. in cooperation with Hydrotox GmbH who also carried out the previous feasibility study (Groß et al 2011). In the ongoing project, examples shall be calculated according to a prioritisation according to the harmonised decision tree to judge the relevance and impact of cumulative exposure on the environmental risk assessment (mid 2013). Also legal aspects of possible decision options during active substance evaluation and product authorisation for identified risks for a cumulative risk assessment shall be discussed in the sequel of this project (mid 2013). A first draft of the guidance document shall be available for discussion in autumn/winter 2013.
H2. Cumulative exposure assessment, Human health. The concerns are the same as for E2. However, there is even less available experience, and no substantial background research. The results of an OECD biocides task force questionnaire on approaches to cumulative exposure assessments in member states will be discussed in September 2012. This will provide further insights in the prospects for guidance. If possible, experiences gained from E2 should be incorporated in future work on H2. Accordingly, a first step way forward could be also here to provide general principles and criteria for triggering a cumulative exposure assessment.
Annexes
BPR guidance for mixture toxicity and cumulative exposure - in depth analysis
Annex I Approach and scope
To further characterise the BPR scope on cumulative and synergistic effects, the different proposed guidance packages in Table 1 are organized relative to each other in Figure 1 according to chemical complexity (horizontal dimension) and use complexity (vertical dimension).
Figure 1. Relative scope of BPR guidance for cumulative and synergistic effects. The spatiotemporal scope is always the same, i.e. for the full life cycle of the product(s)/substances including environmental, occupational and residential exposures, taking into account degradation products. The regulatory scope as set down in the legal text of the BPR is also always the same, i.e. active substances and products regulated under the BPD and later under the BPR.
The lower left quadrant in Figure 1 represents the scope of the typical regulatory approach where individual substance and uses are considered separately. The upper right quadrant represents BPR Article 8.3; cumulative exposure to multiple actives. It should be noted that moving from bottom to top on the right hand side of Figure 1 only represents an increase in use and exposure complexity, and not necessarily an increase in chemical complexity. This is because the risk assessment of the single product should be for all "relevant" substances in the product, whereas for cumulative exposure multiple actives it is stated in Article 8.3 that only different active substances should be considered. On the other hand, cumulative exposure in the upper left quadrant might again apply to any "relevant" substance(s) in the products, although it can be speculated that in practice only active substances will be considered here.
The scope of the projects in terms of exposure complexity and chemical complexity will thus change when moving between the different projects (Fig. 1), and it is possible that the exact definitions of cumulative and synergistic effects might change depending on context. In any case knowledge and experiences gained in the different projects should of course be used for cross fertilisation to facilitate the overall progress.