Are Structural Analogues to Bisphenol A Safe Alternatives?

TLDR

Bisphenol A is widely used and suspected of low‑dose endocrine effects, prompting a need for safer alternatives, as structural analogues are already present in foods and humans. The study aimed to compare the endocrine hazards of BPA analogues BPB, BPE, BPF, BPS, and HPP with BPA. In vitro assays of steroidogenesis, estrogen/androgen receptor activity, and biomarker effects, complemented by QSAR modeling, were used to assess the compounds. All analogues produced estrogenic and antiandrogenic effects comparable to BPA, with BPS showing lower estrogenic activity but higher progesterone efficacy; compound‑specific differences in corticosteroid synthesis, DNA damage, carcinogenicity, oxidative stress, metabolic and skin sensitization effects were observed, indicating endocrine disruption and caution in substituting BPA.

Abstract

Background: Bisphenol A (BPA) is a chemical with widespread human exposure suspected of causing low-dose effects. Thus, a need for developing alternatives to BPA exists. Structural analogues of BPA have already been detected in foods and humans. Due to the structural analogy of the alternatives, there is a risk of effects similar to BPA.Objectives: The aim was to elucidate and compare the hazards of bisphenol B (BPB), bisphenol E (BPE), bisphenol F (BPF), bisphenol S (BPS) and 4-cumylphenol (HPP) to BPA.Methods: In vitro studies on steroidogenesis, receptor activity, and biomarkers of effect, as well as Quantitative Structure-Activity Relationship (QSAR) modeling.Results: All test compounds caused the same qualitative effects on estrogen receptor and androgen receptor activities, and most of the alternatives exhibited potencies within the same range as BPA. Hormone profiles for the compounds indicated a specific mechanism of action on steroidogenesis which generally lead to decreased androgen, and increased estrogen and progestagen levels. Differential effects on corticosteroid synthesis were observed suggesting a compound-specific mechanism. Overall, BPS was less estrogenic and antiandrogenic than BPA, but BPS showed the largest efficacy on 17α-hydroxyprogesterone (17α-OH progesterone). Finally, there were indications of DNA damage, carcinogenicity, oxidative stress, effects on metabolism, and skin sensitization of one or more of the test compounds.Conclusions: Interference with the endocrine system was the predominant effect of the test compounds. A substitution of BPA with these structural analogues should be carried out with caution.