Thyroid endocrine disruption and hepatotoxicity induced by bisphenol AF: Integrated zebrafish embryotoxicity test and deep learning

ABSTRAC T Bisphenol AF (BPAF) is an emerging contaminant prevalent in the environment as one of main substitutes of bisphenol A (BPA). It was found that BPAF exhibited estrogenic effects in zebrafish larvae in our previous study, while little is known about its effects on the thyroid and liver. A 7 d zebrafish embryotoxicity test was conducted to study the poten-tial thyroid disruption and hepatotoxicity of BPAF. BPAF decreased levels of thyroid hormones and deiodinases but increased expressions of transthyretin at 12.5 and 125 mu g/L after 7 d exposure, indicating that both the metabolism and transport of thyroid hormones were perturbed. The thyroid hormone receptor (TR) levels decreased significantly upon exposure to >_12.5 mu g/L BPAF, implying that BPAF acts as a TR antagonist, which coincided well with the pre-diction from the Direct Message Passing Neural Network. The liver impairment (mainly cell necrosis of hepatocytes) and apoptosis were triggered by 125 mu g/L and >_12.5 mu g/L BPAF respectively, accompanied by the increased activities of caspase 3 and caspase 9. Thus BPAF might not be a safe alternative to BPA given the thyroid and liver toxicity. DMPNN appears useful to screen for thyroid disrupting activity from molecular structures.