WEIGHT OF EVIDENCE REVIEW TO DETERMINE ENDOCRINE DISRUPTING PROPERTIES OF ACTIVE SUBSTANCES

摘要

The European legislation on plant protection products (Regulation (EC) No. 1107/2009) sets out new, stricter, criteria for approval of active substances and includes the assessment of endocrine disrupting properties. Active substances that are endocrine disruptors will not be approved under the new regulation unless there is negligible exposure to humans and non-target species. In addition to this, endocrine disrupting substances approved because of negligible exposure will become candidates for substitution with less hazardous substances during the authorisation stage at Member State level. The burden of proof is placed on the notifier. One way of determining whether a substance is an endocrine disrupter is to use a weight of evidence (WoE) approach to evaluate all available data. We have reviewed two published WoE frameworks for the assessment of endocrine disrupting properties of chemicals (CEFIC EMSG 1999, Brown et al. 2001) and combined elements of each into a practical WoE evaluation for active substances in plant protection products. The combined framework consists of four evaluation steps: 1) Study reliability — quality of work undertaken, 2) Study relevance — endpoint relevance to endocrine disruption, 3) Study significance — based on the earlier assessments made for reliability and relevance, and 4) Balance of the weight of evidence, coherence and gap assessment. The method makes full use of endpoints available in standard regulatory toxicity and ecotoxicity studies for indications of endocrine effects and any relevant information in the open literature. Experience indicates that regulatory studies required for product approval will identify indicative endocrine disruption, but targeted supporting in vitro and in vivo studies (either from open literature or commissioned) are required to confirm an endocrine mode of action for any effects that are observed. This approach provides substantive, robust evidence for notifiers and regulators to prioritise substances under the new regulatory requirements.