文章基本信息

标题：Scientific Opinion on Evaluation of the Toxicological Relevance of Pesticide Metabolites for Dietary Risk Assessment
本地全文：下载
作者：Jos Boesten ; Claudia Bolognesi ; Theo Brock 等
期刊名称：EFSA Journal
印刷版ISSN：1831-4732
出版年度：2012
卷号：10
期号：7
DOI：10.2903/j.efsa.2012.2799
出版社：European Food Safety Authority (EFSA), Parma
摘要：The European Food Safety Authority (EFSA) asked the Panel on Plant Protection Products and their Residues (PPR) to develop an opinion on approaches to evaluate the toxicological relevance of metabolites and degradates of pesticide active substances in dietary risk assessment. This opinion identifies the threshold of toxicological concern (TTC) concept as an appropriate screening tool. The TTC values for genotoxic and toxic compounds were found to be sufficiently conservative for chronic exposure, as a result of a validation study with a group of pesticides belonging to different chemical classes. Three critical steps were identified in the application of a TTC scheme: 1) the estimate of the level of the metabolite, 2) the evaluation of genotoxicity alerts and 3) the detection of neurotoxic metabolites. Tentative TTC values for acute exposure were established by the PPR Panel by analysis of the lowest 5^th percentiles of No Observed Adverse Effect Levels (NOAELs) used to establish the Acute Reference Doses (ARfD) for the EFSA pesticide data set. Assessment schemes for chronic and acute dietary risk assessment of pesticide metabolites, using the TTC approach and combined (Q)SAR and read across, are proposed. The opinion also proposes how the risk assessment of pesticide metabolites that are stereoisomers should be addressed due to isomer ratio changes reflected in the composition of metabolites. The approach is ready for use, but it is anticipated that on many occasions the outcome of the assessment scheme will be that further testing is needed to reach a firm conclusion on the toxicological relevance of the metabolite. However, the benefit of applying the approach is that it will allow prioritisation of metabolites for subsequent testing.
关键词：Pesticide metabolites; dietary exposure; endocrine disruptor; Quantitative Structure Activity Relationship; (Q)SAR; read-across; stereoisomer ; Threshold of Toxicological Concern (TTC)