Flaws in design, execution and interpretation limit CLARITY-BPA's value for risk assessments of bisphenol A.
Flaws in design, execution and interpretation limit CLARITY-BPA's value for risk assessments of bisphenol A.
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设计、执行和解释方面的缺陷限制了 CLARITY-BPA 对双酚 A 风险评估的价值。
DOI：
10.1111/bcpt.13195
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发表时间：
2019
影响因子：
3.1
通讯作者：
VomSaal,FrederickS
中科院分区：
文献类型：
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作者：
VomSaal,FrederickS
BPA毒性学术和监管见解联盟（Consortium Linking Academic and Regulatory Insights on BPA Toxicity，简称BPA）由美国食品药品监督管理局（FDA）、国家毒理学计划（National Toxicology Program）和国家环境健康科学研究所（National Institute of Environmental Health Sciences）资助的14名学术研究人员组成。双酚A研究需要回答的两个关键问题如下：（1）学术研究者的研究是否会显示低剂量双酚A（BPA）的影响，而FDA进行的核心指南研究仅显示高剂量的毒性作用？(2)学术研究人员是否能够用在FDA毒理学中心饲养和治疗的动物复制他们之前的许多研究？实验设计和执行中的几个缺陷使实验偏向于未发现显著结果（2型错误）：（1）使用雌激素不敏感的NCTR CD‐SD大鼠，（2）在整个生命周期中使用每日强制灌胃BPA给药程序，（3）未纳入非灌胃阴性对照，（4）缺乏对BPA污染动物的全面检查。尽管存在这些缺陷，但在一些由BPA学术研究人员进行的实验中，以及在FDA的核心研究中，存在显著的低剂量效应，但这些都被FDA忽视了。因此，在公布了BPA的核心部分的结果后，FDA立即发表了一份声明，结论是BPA是“安全的”，他们忽略了非单调的剂量反应关系。FDA不应该仅仅基于过时的指南研究来进行BPA风险评估，而是应该基于大量（约8000）文献记录了BPA对动物和人类造成的类似健康危害。
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.