Achieving CLARITY on bisphenol A, brain and behaviour.

There is perhaps no endocrine disrupting chemical more controversial than bisphenol A (BPA). Comprising a high-volume production chemical used in a variety of applications, BPA has been linked to a litany of adverse health-related outcomes, including effects on brain sexual differentiation and behaviour. Risk assessors preferentially rely on classical guideline-compliant toxicity studies over studies published by academic scientists, and have generally downplayed concerns about the potential risks that BPA poses to human health. It has been argued, however, that, because traditional toxicity studies rarely contain neural endpoints, and only a paucity of endocrine-sensitive endpoints, they are incapable of fully evaluating harm. To address current controversies on the safety of BPA, the United States National Institute of Environmental Health Sciences, the National Toxicology Program (NTP), and the US Food and Drug Administration established the Consortium Linking Academic and Regulatory Insights on BPA Toxicity (CLARITY-BPA). CLARITY-BPA performed a classical regulatory-style toxicology study (Core study) in conjunction with multiple behavioural, molecular and cellular studies conducted by academic laboratories (grantee studies) using a collaboratively devised experimental framework and the same animals and tissues. This review summarises the results from the grantee studies that focused on brain and behaviour. Evidence of altered neuroendocrine development, including age- and sex-specific expression of oestrogen receptor (ER)α and ERβ, and the abrogation of brain and behavioural sexual dimorphisms, supports the conclusion that developmental BPA exposure, even at doses below what regulatory agencies regard as "safe" for humans, contribute to brain and behavioural change. The consistency and the reproducibility of the effects across CLARITY-BPA and prior studies using the same animal strain and almost identical experimental conditions are compelling. Combined analysis of all of the data from the CLARITY-BPA project is underway at the NTP and a final report expected in late 2019.