Regrettable substitution? Comparative study of the effect profile of bisphenol A and eleven analogues in an in vitro test battery

Abstract

Background Bisphenol A (BPA) is currently one of the most widely used synthetic chemicals in the production of a wide range of plastics. Due to its diverse endocrine disrupting potential alternative bisphenols, also referred to as analogues, have been developed. Although the toxicity of BPA is well studied, the (eco)toxicological effects of the bisphenol analogues are largely unknown. The similar molecular structure of the analogues suggests comparable toxicological effects. This study aims to extend the (eco)toxicological knowledge on the bisphenol analogues by evaluating eleven bisphenol analogues compared to the reference substance BPA in in vitro bioassays. The examined endpoints are endocrine potential on three nuclear receptors in recombinant yeast cells of Saccharomyces cerevisiae, baseline toxicity (also referred to as non-specific toxicity, describing the minimal toxicity of a chemical) in the luminescent bacterium Aliivibrio fischeri, and mutagenicity in two strains of Salmonella typhimurium. Results Bisphenol A showed estrogenic and anti-androgenic activity at EC50 concentrations of 0.516 mg/L (2.26 × 10–6 M) and 1.06 mg/L (4.63 × 10–6 M), respectively. The assays confirmed notable estrogenic and anti-androgenic activity for the vast majority of analogues in comparable, and often higher, efficacies to BPA. Some analogues showed anti-estrogenic instead of estrogenic activity in a range from 0.789 mg/L (1.45 × 10–6 M; TBBPA) to 2.69 mg/L (2.46 × 10–6 M; BADGE). The baseline toxicity of the analogues revealed a similar tendency of comparable to more prominent effects compared to BPA, ranging from 5.81 mg/L (1.73 × 10–5 M; BPAF) to 39.1 mg/L (1.56 × 10–4 M; BPS). There was no evidence of mutagenicity found. Conclusion The examined bisphenol analogues prove to be equally, if not more, problematic in endocrine activities than the reference bisphenol A. Based on these results, the tested bisphenols cannot be regarded as safer alternatives and reinforce the notion of bisphenol analogues being considered as regrettable substitutions.