Assessing dose-response relationships for endocrine disrupting chemicals (EDCs): a focus on non-monotonicity.
Assessing dose-response relationships for endocrine disrupting chemicals (EDCs): a focus on non-monotonicity.
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DOI：
10.1186/s12940-015-0029-4
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发表时间：
2015-05-15
期刊：
影响因子：
--
通讯作者：
Vandenberg LN
中科院分区：
文献类型：
--
作者：
Zoeller RT;Vandenberg LN
监管毒理学的基本原则是所有化学品都是有毒的，其影响的严重程度与暴露水平成正比。一个辅助假设是，低于最低观察到的不良影响水平 (LOAEL) 的暴露不会产生任何影响，要么是因为不存在影响，要么是因为它们在统计上无法解决，这意味着它们不会产生不利影响。干扰激素的化学物质在两个重要方面违反了这些原则：剂量-反应关系可能是非单调的，这已在数百项内分泌干扰化学物质（EDC）研究中得到报道；且影响通常在最低有害空气浓度以下观察到，包括所有检查 EDC 的环境流行病学研究。拉加德等人认识到这个问题的重要性。发表了第一个定性评估非单调剂量反应（NMDR）关系的提案，以用于风险评估。他们的提议代表了在评估用于风险评估的复杂数据集方面向前迈出了重要一步。在这里，我们对拉加德提案中我们认为需要更严格评估的三个要素进行评论，并提出我们的论点：1）使用 Klimisch 评分来评估研究质量，2）在没有主题专家知识和意见的情况下评估研究质量的概念，以及 3）在考虑用于风险评估之前建立 NMDR 的生物学合理性的要求。我们提出基于证据的逻辑论证：1）应放弃使用 Klimisch 评分来评估研究质量； 2）评估研究质量需要特定领域的专家； 3) 接受可观察到的、统计上有效的现象不需要了解机制。我们希望为有关 NMDR 对风险评估影响的重要且持续的辩论做出贡献，并提出积极的建议。
The fundamental principle in regulatory toxicology is that all chemicals are toxic and that the severity of effect is proportional to the exposure level. An ancillary assumption is that there are no effects at exposures below the lowest observed adverse effect level (LOAEL), either because no effects exist or because they are not statistically resolvable, implying that they would not be adverse. Chemicals that interfere with hormones violate these principles in two important ways: dose–response relationships can be non-monotonic, which have been reported in hundreds of studies of endocrine disrupting chemicals (EDCs); and effects are often observed below the LOAEL, including all environmental epidemiological studies examining EDCs. In recognition of the importance of this issue, Lagarde et al. have published the first proposal to qualitatively assess non-monotonic dose response (NMDR) relationships for use in risk assessments. Their proposal represents a significant step forward in the evaluation of complex datasets for use in risk assessments. Here, we comment on three elements of the Lagarde proposal that we feel need to be assessed more critically and present our arguments: 1) the use of Klimisch scores to evaluate study quality, 2) the concept of evaluating study quality without topical experts’ knowledge and opinions, and 3) the requirement of establishing the biological plausibility of an NMDR before consideration for use in risk assessment. We present evidence-based logical arguments that 1) the use of the Klimisch score should be abandoned for assessing study quality; 2) evaluating study quality requires experts in the specific field; and 3) an understanding of mechanisms should not be required to accept observable, statistically valid phenomena. It is our hope to contribute to the important and ongoing debate about the impact of NMDRs on risk assessment with positive suggestions.
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影响因子：
10.4
作者：
Krauth D;Woodruff TJ;Bero L
通讯作者：
Bero L
影响因子：
10.4
作者：
Myers JP;vom Saal FS;Akingbemi BT;Arizono K;Belcher S;Colborn T;Chahoud I;Crain DA;Farabollini F;Guillette LJ Jr;Hassold T;Ho SM;Hunt PA;Iguchi T;Jobling S;Kanno J;Laufer H;Marcus M;McLachlan JA;Nadal A;Oehlmann J;Olea N;Palanza P;Parmigiani S;Rubin BS;Schoenfelder G;Sonnenschein C;Soto AM;Talsness CE;Taylor JA;Vandenberg LN;Vandenbergh JG;Vogel S;Watson CS;Welshons WV;Zoeller RT
通讯作者：
Zoeller RT
影响因子：
4.6
作者：
Fauquier, Teddy;Chatonnet, Fabrice;Flamant, Frederic
通讯作者：
Flamant, Frederic
影响因子：
3.4
作者：
Klimisch, HJ;Andreae, M;Tillmann, U
通讯作者：
Tillmann, U
DOI：
10.1016/j.reprotox.2013.02.002
发表时间：
2013-07
期刊：
Reproductive toxicology (Elmsford, N.Y.)
影响因子：
--
作者：
Vandenberg LN;Colborn T;Hayes TB;Heindel JJ;Jacobs DR Jr;Lee DH;Myers JP;Shioda T;Soto AM;vom Saal FS;Welshons WV;Zoeller RT
通讯作者：
Zoeller RT