CLARITY-BPA Core Study: Analysis for non-monotonic dose-responses and biological relevance. (September 2019)

• Record Type: Journal Article
• Authors: Badding, Melissa A.; Barraj, Leila; Williams, Amy L.; Scrafford, Carolyn; Reiss, Richard
• Is Part Of: Food and chemical toxicology. Volume 131(2019)
• Publication Date: 2019-09
• Subjects: Bisphenol A -- BPA -- Non-monotonic dose response -- Mammary gland -- Endocrine disruption -- Low dose; Toxicology -- Periodicals; Food poisoning -- Periodicals; Food Poisoning -- Periodicals; Toxicology -- Periodicals; Toxicologie -- Périodiques; Intoxications alimentaires -- Périodiques; Food poisoning; Toxicology; Periodicals; Electronic journals; 615.9
• DOI: 10.1016/j.fct.2019.06.001
• Languages: English
• ISSNs: 0278-6915

Abstract

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. Highlights: Conducted a NMDR analysis of data from the CLARITY-BPA Core Study. BPA has been proposed as having potential NMDR effects, and the Core Study provides a unique opportunity to analyze NMDR. Applied the systematic 6 checkpoint NMDR analysis developed by Varret et al. (2018) to statistically significant findings. Only 2 of the 81 Core Study statistically significant findings met at least 5 of the 6 Varret checkpoint requirements. Further evaluation of the findings showed an overall lack of consistency and concordance with other BPA data.