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

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 The FDA should not base its BPA risk assessment only on outdated guideline studies, but instead on the vast (~8000) number of publications documenting the similar health hazards BPA poses to animals and humans.