Evidence for Bisphenol B Endocrine Properties: Scientific and Regulatory Perspectives

Background: The substitution of bisphenol A (BPA) by bisphenol B (BPB), a very close structural analog, stresses the need to assess its potential endocrine properties.

Objective: This analysis aimed to investigate whether BPB has endocrine disruptive properties in humans and in wildlife as defined by the World Health Organization (WHO) definition used in the regulatory field, that is, a) adverse effects, b) endocrine activity, and c) plausible mechanistic links between the observed endocrine activity and adverse effects.

Methods: We conducted a systematic review to identify BPB adverse effects and endocrine activities by focusing on animal models and in vitro mechanistic studies. The results were grouped by modality (estrogenic, androgenic, thyroid hormone, steroidogenesis-related, or other endocrine activities). After critical analysis of results, lines of evidence were built using a weight-of-evidence approach to establish a biologically plausible link. In addition, the ratio of BPA to BPB potency was reported from studies investigating both bisphenols.

Results: Among the 36 articles included in the analysis, 3 subchronic studies consistently reported effects of BPB on reproductive function. In rats, the 28-d and 48-week studies showed alteration of spermatogenesis associated with a lower height of the seminiferous tubules, the alteration of several sperm parameters, and a weight loss for the testis, epididymis, and seminal vesicles. In zebrafish, the results of a 21-d reproductive study demonstrated that exposed fish had a lower egg production and a lower hatching rate and viability. The in vitro and in vivo mechanistic data consistently demonstrated BPB's capacity to decrease testosterone production and to exert an estrogenic-like activity similar to or greater than BPA's, both pathways being potentially responsible for spermatogenesis impairment in rats and fish.

Conclusion: The available in vivo, ex vivo, and in vitro data, although limited, coherently indicates that BPB meets the WHO definition of an endocrine disrupting chemical currently used in a regulatory context. https://doi.org/10.1289/EHP5200.