Introduction: Endocrine disruptors, such as bisphenols (e.g. BPA and its analogues), interfere with hormonal homeostasis and physiological processes. The objective of this study was to investigate the detrimental effects of BPA and selected analogues (BPAF, BPF, BPS) on the model organism Caenorhabditis elegans.

Methods: The effects of embryonic exposure to BPA, BPAF, BPF, and BPS were studied in a reference strain C. elegans N2 and two mutant strains, namely bli-1 and dpy-13. Embryos were exposed to 0,5; 1; and 5 µM of each compound for 4 hours. After exposure, hatching, oviposition, locomotor activity, and habituation to anterior touch were assessed to identify sensitive genotypes and evaluate their suitability for detecting subtle toxic effects.

Results: In WT, all tested bisphenols significantly reduced hatching already at 0,5 µM. C. elegans dpy-13 was the most sensitive for hatching, with the strongest effect observed at 5 µM of BPF, where median hatching decreased to 12,5%. During oviposition, dpy-13 showed relative resistance to BPA, but marked sensitivity to its analogues. BPAF significantly reduced egg laying from 0,5 µM, while BPF and BPS exhibited this effect at 1 µM. C. elegans bli-1 was the most sensitive in habituation, showing a dose-dependent increase in the number of anterior touches required after all bisphenols tested. In particular, at concentration of 0,5 µM BPS, the median reached 37,5 touches compared to 27 observed in WT.

Conclusions: Comparative analysis revealed that the adverse physiological impacts of BPA analogues were not only comparable to BPA but, in several cases, more potent. Findings using bli-1 and dpy-13 mutants demonstrate that specific cuticle architecture plays a key role in modulating the biological impact of these bisphenols. This study improves the risk assessment of BPA substitutes and identifies specific C. elegans mutants as sensitive tools for screening endocrine disruptors at environmental concentrations.