Risk assessment of 'endocrine substances': guidance on identifying endocrine disruptors

The European regulation on plant protection products (1107/2009) and other related legislation only support the marketing and use of chemical products on the basis that they do not induce endocrine disruption in humans or wildlife species. This legislation would appear to make the assumption that endocrine active chemicals should be managed differently from other chemicals presumably due to an assumed lack of a threshold for adverse effects. In the absence of agreed scientific criteria and guidance on how to identify and evaluate endocrine activity and disruption within these pieces of legislation, a European Centre for Ecotoxicology and Toxicology of Chemicals (ECETOC) task force was formed to provide scientific criteria that may be used within the context of these three legislative documents. The first ECETOC technical report and associated workshop, held in 2009, presented a science-based concept on how to identify endocrine activity and disrupting properties of chemicals for both human health and the environment. Specific scientific criteria for the determination of endocrine activity and disrupting properties that integrate information from both regulatory toxicity studies and mechanistic/screening studies were proposed. These criteria combined the nature of the adverse effects detected in studies which give concern for endocrine toxicity with an understanding of the mode of action of toxicity so that adverse effects can be explained scientifically. A key element in the data evaluation is the consideration of all available information in a weight-of-evidence approach. Both sets of data (evidence of the adverse effect in apical studies and conclusive mode of action knowledge) are essential in order to correctly identify endocrine disruption according to accepted definitions. As the legislation seeks to regulate chemicals on a mode of action rather than the more traditional approach of adverse endpoints, then conclusive evidence of the mode of action of concern should be presented. From a human safety perspective and in the absence of any compelling data that endocrine active chemicals exert their adverse effects through anything other than a threshold mechanism there is no scientific justification for not using a margin of exposure approach to risk assessment in order to best protect human health.