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Grouping of endocrine disrupting chemicals for mixture risk assessment - Evidence from a rat study.
Environment International ( IF 11.8 ) Pub Date : 2020-06-24 , DOI: 10.1016/j.envint.2020.105870
Sofie Christiansen 1 , Marta Axelstad 1 , Martin Scholze 2 , Hanna K L Johansson 1 , Ulla Hass 1 , Karen Mandrup 1 , Henrik Lauritz Frandsen 3 , Hanne Frederiksen 4 , Louise Krag Isling 1 , Julie Boberg 1
Affiliation  

Exposure to mixtures of endocrine disrupting chemicals may contribute to the rising incidence of hormone-related diseases in humans. Real-life mixtures are complex, comprised of chemicals with mixed modes of action, and essential knowledge is often lacking on how to group such chemicals into cumulative assessment groups, which is an essential prerequisite to conduct a chemical mixture risk assessment.

We investigated if mixtures of chemicals with diverse endocrine modes of action can cause mixture effects on hormone sensitive endpoints in developing and adult rat offspring after perinatal exposure. Wistar rats were exposed during pregnancy and lactation simultaneously to either bisphenol A and butylparaben (Emix), diethylhexyl phthalate and procymidone (Amix), or a mixture of all four substances (Totalmix). In male offspring, the anogenital distance was significantly reduced and nipple retention increased in animals exposed to Amix and Totalmix, and the mixture effects were well approximated by the dose addition model. The combination of Amix and Emix responded with more marked changes on these and other endocrine-sensitive endpoints than each binary mixture on its own. Sperm counts were reduced by all exposures. These experimental outcomes suggest that the grouping of chemicals for mixture risk assessment should be based on common health outcomes rather than only similar modes or mechanisms of action. Mechanistic-based approaches such as the concept of Adverse Outcome Pathway (AOP) can provide important guidance if both the information on shared target tissues and the information on shared mode/mechanism of action are taken into account.



中文翻译:

内分泌干​​扰化学物质分组以进行混合物风险评估-来自大鼠研究的证据。

暴露于破坏内分泌化学物质的混合物中可能会导致人类激素相关疾病的发病率上升。现实生活中的混合物很复杂,由具有多种作用方式的化学物质组成,通常缺乏关于如何将这些化学物质归为累积评估组的基本知识,这是进行化学混合物风险评估的必要前提。

我们调查了具有多种内分泌作用方式的化学物质混合物是否会对围产期暴露后的发育中和成年大鼠后代的激素敏感终点产生混合效应。Wistar大鼠在妊娠和哺乳期间同时暴露于双酚A和对羟基苯甲酸丁酯(Emix),邻苯二甲酸二乙己基酯和嘧啶酮(Amix)或所有四种物质的混合物(Totalmix)。在雄性后代中,暴露于Amix和Totalmix的动物的生殖器距离显着缩短,乳头保留增加,并且通过剂量添加模型可以很好地近似混合物的效果。与每种二元混合物本身相比,Amix和Emix的组合在这些和其他对内分泌敏感的终点上的反应更显着。所有接触都会减少精子数量。这些实验结果表明,用于混合物风险评估的化学药品的分类应基于共同的健康结果,而不仅仅是相似的作用方式或作用机制。如果同时考虑有关共享目标组织的信息和有关共享作用方式/机制的信息,那么基于机械的方法(例如不良结果途径(AOP)的概念)可以提供重要的指导。

更新日期:2020-06-24
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