UK issued guidance on assessing genotoxicity equivalence of pesticide technical materials

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’. The scope of the UK COM guidance includes assessing the genotoxicity equivalence of pesticide technical materials.

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.

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. CRD advises the following points should be noted:

1. 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.

2. 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.

3. 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.

4. Where possible and practical, CRD advocates testing the isolated or synthesised impurity rather than the technical substance.