Regulatory Update 19/2012
Issued: 21 May 2012
Assessment of the equivalence of pesticide technical materials (pure active substance plus impurities) from different sources, eg from different manufacturers, is a requirement under EU legislation. Technical material from different sources may contain different impurities or different levels of impurities. It is important to know whether, for the same active substance, technical materials from different sources pose a comparable degree of hazard for human health and for the environment. Evaluation of the mutagenic potential of impurities is one of the fundamental human health considerations when assessing equivalence of pesticide technical materials from different sources.
CRD Regulatory Position
CRD ’s general approach to the assessment of the equivalence of pesticide technical materials is to follow the EU guidance on this issue produced by the European Commission in June 2011 see: SANCO/110597/2003- rev.9 on Commission website. This guidance has been established to support the harmonised procedure for assessment of equivalence under Regulation (EC) 1107/2009 so that member States can reach common decisions.
Appendix IV of this SANCO guidance addresses the need for additional toxicity information, including genotoxicity studies to determine mutagenic hazard, in order to assess the equivalence of technical material from a new source compared to technical material from the reference source.
Impact of recent UK Committee on Mutagenicity “interim guidance”
The UK Committee on Mutagenicity of Chemicals in Food, Consumer Products and the Environment (UK COM) has recently produced (April 2012) ‘Interim Guidance on a Strategy for Genotoxicity Testing and Mutagenic Hazard Assessment of Impurities in Chemical Substances’, see statement at COM/12/S2
The scope of the UK COM guidance includes assessing the genotoxicity equivalence of pesticide technical materials. Although in broad terms there are similarities between the UK COM guidance and the EC SANCO guidance of 2011, there are also some notable differences.
Those concerned with this issue should familiarise themselves with both the SANCO (2011) and UK COM (2012) guidance. CRD regards the latter as complementing the former. In this respect, the following points should be noted:
- Both UK COM and SANCO advocate the use of the TTC (threshold of toxicological concern), and UK COM recommends a TTC value for deciding if genotoxicological assessment is necessary. CRD considers that the TTC approach can only be applied case-by-case until the EU has agreed one or more TTC values for assessing the equivalence of pesticide technical materials.
- Although the UK COM guidance indicates that no genotoxicity testing is required for an impurity giving a negative Quantitative Structure Activity Relationships (QSAR) result for genotoxicity, CRD would require substantial and compelling evidence to accept such an approach which is not in line with the SANCO guidance.
- CRD agrees that there are circumstances in which the UK COM approach of only two in vitro genotoxicity assays (Ames and in vitro mammalian cell micronucleus), might be sufficient, rather than Ames, mammalian cell gene mutation and in vitro cytogenetics. If the two study approach is used, a short case explaining why this is appropriate should be submitted. [Note: this two study approach is compatible with a recently proposed view of an EFSA Scientific Committee ( Link to view on EFSA site ), but might not be accepted by all Member States.]
- Where possible and practical, CRD advocates testing the isolated or synthesised impurity rather than the technical substance.
If you have any questions regarding this issue, please contact CRD Applicant Enquiries:
Postal address: Applicant Enquiry Team, Chemicals Regulation Directorate, HSE, Room 213 Mallard House, Kings Pool, 3 Peasholme Green, York, YO1 7PX, UK