Kortenkamp Andreas
The School of Pharmacy, University of London, London, United Kingdom.
Environ Health Perspect. 2007 Dec;115 Suppl 1(Suppl 1):98-105. doi: 10.1289/ehp.9357.
In the last 10 years, good evidence has become available to show that the combined effects of endocrine disruptors (EDs) belonging to the same category (e.g., estrogenic, antiandrogenic, or thyroid-disrupting agents) can be predicted by using dose addition. This is true for a variety of end points representing a wide range of organizational levels and biological complexity. Combinations of EDs are able to produce significant effect, even when each chemical is present at low doses that individually do not induce observable effects. However, comparatively little is known about mixtures composed of chemicals from different classes of EDs. Nevertheless, I argue that the accumulated evidence seriously undermines continuation with the customary chemical-by-chemical approach to risk assessment for EDs. Instead, we should seriously consider group-wise regulation of classes of EDs. Great care should be taken to define such classes by using suitable similarity criteria. Criteria should focus on common effects, rather than common mechanisms. In this review I also highlight research needs and identify the lack of information about exposure scenarios as a knowledge gap that seriously hampers progress with ED risk assessment. Future research should focus on investigating the effects of combinations of EDs from different categories, with considerable emphasis on elucidating mechanisms. This strategy may lead to better-defined criteria for grouping EDs for regulatory purposes. Also, steps should be taken to develop dedicated mixtures exposure assessment for EDs.
在过去十年中,已有充分证据表明,通过剂量相加法可以预测属于同一类别的内分泌干扰物(EDs)(例如,雌激素类、抗雄激素类或甲状腺干扰剂)的联合效应。对于代表广泛组织水平和生物复杂性的各种终点而言,情况确实如此。即使每种化学物质的剂量很低,单独使用时不会产生可观察到的影响,但EDs的组合仍能够产生显著影响。然而,对于由不同类别的EDs组成的混合物,我们所知相对较少。尽管如此,我认为积累的证据严重削弱了继续采用传统的逐个化学品进行EDs风险评估的方法。相反,我们应该认真考虑对EDs类别进行分组监管。应格外谨慎地使用合适的相似性标准来定义此类类别。标准应侧重于共同效应,而非共同机制。在本综述中,我还强调了研究需求,并指出缺乏有关暴露场景的信息是一个严重阻碍EDs风险评估进展的知识空白。未来的研究应侧重于调查不同类别的EDs组合的影响,尤其要着重阐明其作用机制。这一策略可能会为监管目的对EDs进行分组制定出更明确的标准。此外,应采取措施为EDs开发专门的混合物暴露评估方法。