Nonmonotonic Dose-Response Curves Occur in Dose Ranges That Are Relevant to Regulatory Decision-Making.
Nonmonotonic Dose-Response Curves Occur in Dose Ranges That Are Relevant to Regulatory Decision-Making.
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DOI：
10.1177/1559325818798282
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发表时间：
2018-07
期刊：
影响因子：
--
通讯作者：
Vandenberg LN
中科院分区：
文献类型：
--
作者：
Hill CE;Myers JP;Vandenberg LN
非单调剂量反应曲线（NMDRC）出现在细胞、组织、动物和人群中，以响应营养素、维生素、药理化合物、激素和内分泌干扰化学品（EDC）。然而，监管机构认为NMDRC并不常见，未发现不良结局，并且与EDCs的监管无关。在线性剂量反应模型下，高剂量测试用于外推到预期对人类照射“安全”的较低剂量。低于毒理学无明显不良作用水平（NOAEL）的NMDRC将推翻一个基本假设，即高剂量危害可用于预测低剂量安全性。在这篇评论中，我们提供了NMDRC的例子，并讨论了它们在剂量反应曲线不同部分的存在如何影响监管决策。我们提供的证据表明，对于白藜芦醇、氯菊酯、百菌清和邻苯二甲酸酯（如DEHP）等化学品，NMDRC确实发生在NOAEL剂量以下，甚至低于“安全”参考剂量。我们还简要讨论了最近的研究，BPA的乳腺癌只在大鼠暴露于最低BPA剂量。我们总结了我们的评论，建议如何NMDRC应被承认和利用，以改善监管毒性测试和计算的参考剂量，是公共卫生保护。
Non-monotonic dose response curves (NMDRCs) occur in cells, tissues, animals and human populations in response to nutrients, vitamins, pharmacological compounds, hormones and endocrine disrupting chemicals (EDCs). Yet, regulatory agencies have argued that NMDRCs are not common, are not found for adverse outcomes, and are not relevant for regulation of EDCs. Under the linear dose response model, high dose testing is used to extrapolate to lower doses that are anticipated to be ‘safe’ for human exposures. NMDRCs that occur below the toxicological no-observed-adverse-effect level (NOAEL) would falsify a fundamental assumption, that high dose hazards can be used to predict low dose safety. In this commentary, we provide examples of NMDRCs and discuss how their presence in different portions of the dose response curve might affect regulatory decisions. We provide evidence that NMDRCs do occur below the NOAEL dose, and even below the ‘safe’ reference dose, for chemicals such as resveratrol, permethrin, chlorothalonil, and phthalates such as DEHP. We also briefly discuss the recent CLARITY-BPA study, which reported mammary adenocarcinomas only in rats exposed to the lowest BPA dose. We conclude our commentary with suggestions for how NMDRCs should be acknowledged and utilized to improve regulatory toxicity testing and in the calculation of reference doses that are public health protective.
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DOI：
10.1186/s12940-015-0029-4
发表时间：
2015-05-15
期刊：
Environmental health : a global access science source
影响因子：
--
作者：
Zoeller RT;Vandenberg LN
通讯作者：
Vandenberg LN
非单调剂量反应关系和内分泌破坏者：一种定性评估方法。
DOI：
10.1186/1476-069x-14-13
发表时间：
2015-02-11
期刊：
Environmental health : a global access science source
影响因子：
--
作者：
Lagarde F;Beausoleil C;Belcher SM;Belzunces LP;Emond C;Guerbet M;Rousselle C
通讯作者：
Rousselle C
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
影响因子：
8.2
作者：
Beronius A;Vandenberg LN
通讯作者：
Vandenberg LN
影响因子：
3.4
作者：
Bloomquist, JR;Barlow, RL;Kirby, ML
通讯作者：
Kirby, ML