Data integration, analysis, and interpretation of eight academic CLARITY-BPA studies

Reprod Toxicol. 2020 Dec:98:29-60. doi: 10.1016/j.reprotox.2020.05.014. Epub 2020 Jul 16.

Abstract

"Consortium Linking Academic and Regulatory Insights on BPA Toxicity" (CLARITY-BPA) was a comprehensive "industry-standard" Good Laboratory Practice (GLP)-compliant 2-year chronic exposure study of bisphenol A (BPA) toxicity that was supplemented by hypothesis-driven independent investigator-initiated studies. The investigator-initiated studies were focused on integrating disease-associated, molecular, and physiological endpoints previously found by academic scientists into an industry standard guideline-compliant toxicity study. Thus, the goal of this collaboration was to provide a more comprehensive dataset upon which to base safety standards and to determine whether industry-standard tests are as sensitive and predictive as molecular and disease-associated endpoints. The goal of this report is to integrate the findings from the investigator-initiated studies into a comprehensive overview of the observed impacts of BPA across the multiple organs and systems analyzed. For each organ system, we provide the rationale for the study, an overview of methodology, and summarize major findings. We then compare the results of the CLARITY-BPA studies across organ systems with the results of previous peer-reviewed studies from independent labs. Finally, we discuss potential influences that contributed to differences between studies. Developmental exposure to BPA can lead to adverse effects in multiple organs systems, including the brain, prostate gland, urinary tract, ovary, mammary gland, and heart. As published previously, many effects were at the lowest dose tested, 2.5μg/kg /day, and many of the responses were non-monotonic. Because the low dose of BPA affected endpoints in the same animals across organs evaluated in different labs, we conclude that these are biologically - and toxicologically - relevant.

Keywords: Bisphenol A; CLARITY-BPA; EDC; Endocrine disruptor; GLP; Guideline study; Systemic effects.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Behavior, Animal / drug effects
  • Benzhydryl Compounds / toxicity*
  • DNA Methylation
  • Endocrine Disruptors / toxicity*
  • Female
  • Gene Expression Regulation, Developmental / drug effects
  • Heart / drug effects
  • Heart / growth & development
  • Male
  • Mammary Glands, Animal / drug effects
  • Mammary Glands, Animal / growth & development
  • Maternal-Fetal Exchange*
  • Ovary / drug effects
  • Ovary / growth & development
  • Phenols / toxicity*
  • Pregnancy
  • Prenatal Exposure Delayed Effects / chemically induced*
  • Prenatal Exposure Delayed Effects / genetics
  • Prostate / drug effects
  • Prostate / growth & development
  • Rats, Sprague-Dawley
  • Reproducibility of Results
  • Thyroid Gland / drug effects
  • Thyroid Gland / growth & development
  • Urethra / drug effects
  • Urethra / growth & development

Substances

  • Benzhydryl Compounds
  • Endocrine Disruptors
  • Phenols
  • bisphenol A