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CLARITY-BPA Core Study: Analysis for non-monotonic dose-responses and biological relevance

Author:
Badding, Melissa A., Barraj, Leila, Williams, Amy L., Scrafford, Carolyn, Reiss, Richard
Source:
Food and chemical toxicology 2019 v.131 pp. 110554
ISSN:
0278-6915
Subject:
basophils, bile acids, bisphenol A, dose response, females, males, rats, statistical analysis, toxicology
Abstract:
The results of a large 2-year bisphenol A (BPA) rat study conducted by the NTP, called the CLARITY-BPA Core Study, were recently released. This study addressed some of the toxicological issues associated with BPA, including endocrine disruption and non-monotonic dose responses (NMDR). The study involved oral gavage treatment of rats to BPA at doses of 2.5–25,000 μg/kg-bw/day. To address NMDR, the 81 statistically significant findings (based on the primary statistical tests) from the Core Study were evaluated using a recently published methodology that relies upon six checkpoints to determine if there is evidence for a NMDR. Failure to meet the majority of the checkpoints indicates limited evidence of NMDR. The analysis found that only 2 of the 81 findings met at least 5 of the checkpoints: an increase in percent basophils in stop-dose females and decreased total bile acids in stop-dose males. However, these findings are not concordant or consistent with those of other BPA data. Importantly, none of the endocrine-related or reproductive endpoints fulfilled at least 5 of the checkpoints. This analysis found limited evidence for NMDR associated with BPA treatment in the study. These results are consistent with the conclusions reached in the Core Study report.
Agid:
6474804