Marx-Stoelting P, Niemann L, Ritz V, Ulbrich B, Gall A, Hirsch-Ernst K I, Pfeil R, Solecki R
Bundesinstitut für Risikobewertung (Federal Institute for Risk Assessment), Max-Dohrn-Str 8-10, 10589 Berlin, Germany.
Bundesinstitut für Risikobewertung (Federal Institute for Risk Assessment), Max-Dohrn-Str 8-10, 10589 Berlin, Germany.
Regul Toxicol Pharmacol. 2014 Dec;70(3):590-604. doi: 10.1016/j.yrtph.2014.09.001. Epub 2014 Sep 17.
Recent EU legislation has introduced endocrine disrupting properties as a hazard-based "cut-off" criterion for the approval of active substances as pesticides and biocides. Currently, no specific science-based approach for the assessment of substances with endocrine disrupting properties has been agreed upon, although this new legislation provides interim criteria based on classification and labelling. Different proposals for decision making on potential endocrine disrupting properties in human health risk assessment have been developed by the German Federal Institute for Risk Assessment (BfR) and other regulatory bodies. All these frameworks, although differing with regard to hazard characterisation, include a toxicological assessment of adversity of the effects, the evaluation of underlying modes/mechanisms of action in animals and considerations concerning the relevance of effects to humans. Three options for regulatory decision making were tested upon 39 pesticides for their applicability and to analyze their potential impact on the regulatory status of active substances that are currently approved for use in Europe: Option 1, based purely on hazard identification (adversity, mode of action, and the plausibility that both are related); Option 2, based on hazard identification and additional elements of hazard characterisation (severity and potency); Option 3, based on the interim criteria laid down in the recent EU pesticides legislation. Additionally, the data analysed in this study were used to address the questions, which parts of the endocrine system were affected, which studies were the most sensitive and whether no observed adverse effect levels were observed for substance with ED properties. The results of this exercise represent preliminary categorisations and must not be used as a basis for definitive regulatory decisions. They demonstrate that a combination of criteria for hazard identification with additional criteria of hazard characterisation allows prioritising and differentiating between substances with regard to their regulatory concern. It is proposed to integrate these elements into a decision matrix to be used within a weight of evidence approach for the toxicological categorisation of relevant endocrine disruptors and to consider all parts of the endocrine system for regulatory decision making on endocrine disruption.
欧盟近期的立法引入了内分泌干扰特性，作为基于危害的“截断”标准，用于批准作为农药和生物杀灭剂的活性物质。目前，尽管这项新立法提供了基于分类和标签的临时标准，但尚未就评估具有内分泌干扰特性物质的具体科学方法达成一致。德国联邦风险评估研究所（BfR）和其他监管机构针对人类健康风险评估中潜在内分泌干扰特性的决策制定提出了不同建议。所有这些框架，尽管在危害特征描述方面存在差异，但都包括对效应的有害性进行毒理学评估、对动物体内潜在作用模式/机制的评估以及对效应与人类相关性的考量。针对39种农药测试了三种监管决策选项的适用性，并分析它们对目前在欧洲被批准使用的活性物质监管状态的潜在影响：选项1，纯粹基于危害识别（有害性、作用模式以及两者相关的合理性）；选项2，基于危害识别以及危害特征描述的其他要素（严重性和效力）；选项3，基于欧盟近期农药立法规定的临时标准。此外，本研究中分析的数据用于解决以下问题：内分泌系统的哪些部分受到了影响，哪些研究最为敏感，以及对于具有内分泌干扰特性的物质是否未观察到不良效应水平。本次分析结果仅为初步分类，不得用作最终监管决策的依据。结果表明，将危害识别标准与危害特征描述的其他标准相结合，能够在物质的监管关注度方面进行排序和区分。建议将这些要素整合到一个决策矩阵中，用于在证据权重方法内对相关内分泌干扰物进行毒理学分类，并在关于内分泌干扰的监管决策中考虑内分泌系统的所有部分。
