设计、执行和解释方面的缺陷限制了 CLARITY-BPA 评估双酚 A 风险的价值。

Flaws in design, execution and interpretation limit CLARITY-BPA's value for risk assessments of bisphenol A.

机构信息

Division of Biological Sciences, University of Missouri-Columbia, Columbia, Missouri.

出版信息

Basic Clin Pharmacol Toxicol. 2019 Aug;125 Suppl 3:32-43. doi: 10.1111/bcpt.13195. Epub 2019 Feb 15.

Abstract

The Consortium Linking Academic and Regulatory Insights on BPA Toxicity (CLARITY-BPA) involved the Food and Drug Administration, the National Toxicology Program and 14 academic investigators funded by the National Institute of Environmental Health Sciences. Two key questions to be answered by CLARITY-BPA were as follows: (1) Would the academic investigator studies show effects at low doses of bisphenol A (BPA) while the core guideline study conducted by the FDA only showed toxic effects at high doses? (2) Would the academic investigators be able to replicate their numerous prior studies with animals raised and treated in the FDA's toxicology centre? Several flaws in the design and execution of CLARITY-BPA biased the experiment towards not finding significant results (Type 2 error): (1) use of the oestrogen-insensitive NCTR CD-SD rat, (2) use of a stressful daily gavage BPA administration procedure throughout life, (3) lack of inclusion of non-gavaged negative controls and (4) lack of a comprehensive examination of animals for BPA contamination. In spite of these flaws, in some of the experiments conducted by CLARITY-BPA academic investigators, and also in the FDA's core study, there were significant low-dose effects, but these were ignored by the FDA. Thus, immediately after releasing the results from their core portion of CLARITY-BPA, the FDA issued a statement concluding BPA was "safe," and they ignored non-monotonic dose-response relationships. The FDA should not base its BPA risk assessment only on outdated guideline studies, but instead on the vast (~8000) number of publications documenting the similar health hazards BPA poses to animals and humans.

摘要

“将学术和监管洞察力联系起来以了解双酚 A 毒性的联盟(CLARITY-BPA)”涉及美国食品药品监督管理局、国家毒理学计划和 14 名由美国国立环境卫生科学研究所资助的学术调查人员。CLARITY-BPA 需要回答的两个关键问题如下:(1)学术调查人员的研究是否会在低剂量双酚 A(BPA)下显示出影响,而美国食品药品监督管理局进行的核心指南研究仅显示高剂量时有毒性作用?(2)学术调查人员是否能够复制他们在食品药品监督管理局毒理学中心饲养和处理的动物的许多先前研究?CLARITY-BPA 的设计和执行中的几个缺陷使实验偏向于找不到显著结果(第二类错误):(1)使用雌激素不敏感的 NCTR CD-SD 大鼠,(2)一生中使用有压力的每日灌胃 BPA 给药程序,(3)缺乏非灌胃阴性对照物,以及(4)缺乏对动物的 BPA 污染进行全面检查。尽管存在这些缺陷,但在 CLARITY-BPA 学术调查人员进行的一些实验中,以及在食品药品监督管理局的核心研究中,都有显著的低剂量效应,但这些都被食品药品监督管理局忽略了。因此,食品药品监督管理局在发布 CLARITY-BPA 核心部分的结果后,立即发表声明,称 BPA“安全”,并忽略了非单调剂量反应关系。食品药品监督管理局不应仅根据过时的指南研究来评估 BPA 的风险,而应根据大量(约 8000 篇)记录 BPA 对动物和人类造成类似健康危害的出版物来评估。

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