July 21, 2020
Recording available here
Jerry Heindel (of HEEDS) presented an overview of the CLARITY-BPA program and an introduction to the current publication, “Data integration, analysis, and interpretation of eight academic CLARITY-BPA studies,” to set the stage for the other speakers.
The Consortium Linking Academic and Regulatory Insights on BPA Toxicity (CLARITY-BPA) is 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. This study was funded and coordinated by the US FDA, the National Toxicology Program, and the National Institute of Environmental Health Sciences, Division of Extramural Research and Training. The fourteen funded investigator-initiated studies were focused on integrating disease-associated, molecular, morphological and physiological endpoints previously found by academic scientists into a 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 current publication is to integrate the findings from eight of 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, authors provide the rationale for the study, an overview of methodology, and summarize major findings. They then compare the results of the CLARITY-BPA studies across organ systems with the results of previous peer-reviewed studies from independent labs. They also discuss potential influences that contributed to differences between studies. Finally, they interpret the findings in light of the current regulatory guidelines for BPA.
Gail Prins presented data on the effects of BPA on the prostate. Previous studies from the Prins lab found that BPA exposure during early life increased susceptibility to hormone-driven prostate cancer with aging and this was confirmed in the CLARITY-BPA studies when rats were treated at the FDA facility. Importantly, the greatest effects were at the lowest dose of BPA; 2.5 ug/kg BW. Dr. Prins also finds that the prostate stem cells were altered by chronic low-dose BPA exposure which may be the basis for increased cancer risk.
Ana Soto presented an overview of her project which focused on BPA effects on the mammary gland. This study used both novel and standard quantitative analyses to assess the effects of BPA exposure over critical windows of development. Both of the quantitative methods reveal clear non-monotonic dose response curves, with the administration of lower doses resulting in larger effects on the development of the mammary gland at all-time points.
Cheryl Rosenfeld assessed the recently developed bioinformatics program called mixOmics analyses, which was designed to integrate large ’omics datasets, to integrate data across organs to examine the potential whole-body effects of BPA. This is the first study to use such a whole-body integrative approach across a number of data-sets with multiple investigators and with organs from the same animal. By using this approach, we show that exposure to even a low dose of BPA currently considered safe by the FDA leads to simultaneous effects in multiple organ systems and at all ages examined.
Gail Prins then concluded by presenting the integrated findings from the seven studies which showed positive effects of BPA, including the urethral, ovarian and cardiovascular effects in addition to those overviewed in the webinar. She will then present the key findings from these studies and how the results should be interpreted by regulatory agencies.