Toxicity of bisphenol analogues on the reproductive, nervous, and immune systems, and their relationships to gut microbiome and metabolism: insights from a multi-species comparison

Abstract

Bisphenols are common chemicals found in plastics and epoxy resins. Over the past decades, many studies have shown that bisphenol A (BPA) is a potential endocrine-disrupting chemical that may cause multisystem toxicity. However, the relative safety of BPA analogues is a controversial subject. Herein, we conducted a review of the reproductive toxicity, neurotoxicity, immunotoxicity, metabolic toxicity and gut microbiome toxicity of the BPA analogues in various species, including Caenorhabditis elegans, zebrafish, turtles, sheep, rodents, and humans. In addition, the mechanisms of action were discussed with focus on bisphenol S and bisphenol F. It was found that these BPA analogues exert their toxic effects on different organs and systems through various mechanisms including epigenetic modifications and effects on cell signaling pathways, microbiome, and metabolome in different species. More research is needed to study the relative toxicity of the lesser-known BPA analogues compared to BPA, both systemically and organ specifically, and to better define the underlying mechanisms of action, in particular, the potentials of disrupting microbiome and metabolism.

Keywords:

• Bisphenol A
• bisphenol S
• bisphenol F
• endocrine-disrupting chemical
• reproductive toxicity
• microbiome
• neurotoxicity
• immunotoxicity
• metabolic toxicity

Acknowledgments

The authors greatly appreciate Dr. Steven D. Holladay (Department Head, Professor, Department of Veterinary Biosciences and Diagnostic Imaging at the University of Georgia), Dr. John J. Wagner (Professor & Interim Director of Interdisciplinary Toxicology Program, Dept. of Physiology & Pharmacology at the University of Georgia), and Jacob Steven Siracusa (A senior graduate student in the Department of Veterinary Bioscience and Diagnostic Imaging at the University of Georgia) for their critical comments.

Supplemental material

Supplemental data for this article can be accessed online at http://dx.doi.org/10.1080/10408444.2021.1908224.

Declaration of interest

The author’s affiliation is as shown on the cover page. The institutions with which the authors are affiliated with are academic institutions. The authors have sole responsibility for the writing and content of the paper. None of the authors have been involved in any legal or regulatory matters related to the contents of the paper. This article was funded by NIH R21ES24487, NIH R41DK121553, and USDA National Institute of Food and Agriculture [grant no. 2016-67021-24994/project accession no. 1009090].