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

Abstract

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 potential thyroid disruption and hepatotoxicity of BPAF. BPAF decreased levels of thyroid hormones and deiodinases but increased expressions of transthyretin at 12.5 and 125 μg/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 μg/L BPAF, implying that BPAF acts as a TR antagonist, which coincided well with the prediction from the Direct Message Passing Neural Network. The liver impairment (mainly cell necrosis of hepatocytes) and apoptosis were triggered by 125 μg/L and ≥12.5 μg/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.