Assessment of toxicity and endocrine-disrupting activity of bisphenol analogues during ozone and UV treatments in zebrafish eleutheroembryos

In recent decades, increased regulations on the use of bisphenol A (BPA) have prompted a surge in the use of BPA alternatives. Consequently, a widespread occurrence of BPA substitutes in aquatic environments is currently being detected. While some evidence exists about the degradation of these compounds through various water treatment technologies, the evolution of the resulting toxicity and endocrine-disrupting activity during these processes remains scarcely evaluated. In this study, the acute toxicity and transcriptomic responses in zebrafish eleutheroembryos exposed to selected bisphenols (BPA, bisphenol AF (BPAF) and bisphenol CCl (BPC-Cl)) were assessed during their oxidation by ozone. In addition, the response of zebrafish eleutheroembryos exposed to BPC-Cl treated with UV radiation was also investigated. Results showed that both ozonation and UV treatment effectively reduced the intrinsic toxicity of the studied bisphenols. This was observed with the increase of the survival and swim bladder inflation rates of zebrafish eleutheroembryos, reaching control levels. In concordance with these results, the initially altered mRNA levels in genes related to xenobiotic stimulus (cyp2k18); lipid homeostasis and transport (apoa1a); retinoid metabolism (aldh1a2); neutrophil differentiation (alas1); and oxygen transport (hbae3) in zebrafish eleutheroembryos were generally mitigated during the ozonation and UV treatment of bisphenols. Similarly, the high estrogenicity of these bisphenols, observed by elevated mRNA levels of cyp19a1b, decreased significantly during the ozonation treatment, reaching control levels. On the contrary, an increase in mRNA levels of fads2 and cyp19a1b was observed in animals exposed to BPC-Cl treated with UV radiation. These results suggest that the photolysis products of BPC-Cl may induce disruption of the lipid biosynthesis and estrogenicity. This was further confirmed with RNA-sequencing analysis, which revealed that embryos exposed to BPC-Cl treated with UV radiation presented alterations in mRNA levels of genes specifically related to estrogenic stimulus.