Probing the bioconcentration and metabolism disruption of bisphenol A and its analogues in adult female zebrafish from integrated AutoQSAR and metabolomics studies

Plenty of emerging bisphenol A (BPA) substitutes rise to wait for assessment of bioconcentration and metabolism disruption. Computational methods are useful to fill the data gap in chemical risk assessment, such as automated quantitative structure-activity relationship (AutoQSAR). It is not clear how AutoQSAR performs in predicting the bioconcentration factor (BCF) in adult zebrafish. Herein, AutoQSAR was used to predict the logBCFs of BPA, bisphenol AF (BPAF), bisphenol B, bisphenol F and bisphenol S (BPS). For the test set, a linear relationship was shown between the observed and predicted logBCFs with a slope of 0.97. The predicted logBCFs of these five bisphenols were quite close to their experimental data with a slope of 0.94, suggesting better performance than directed message passing neural networks and EPI Suite with a slope of 0.69 and 0.61, respectively. Thus, AutoQSAR is powerful in modeling logBCFs in fish with minimal time and expertise. To link bioconcentration with metabolic effects, female zebrafish were exposed to BPA, BPAF and BPS for metabolomics analysis. BPA caused a significant disturbance in amino acid metabolism, while BPAF and BPS significantly altered another three metabolic pathways, showing chemical-specific responses. BPAF with the highest logBCF elicited the strongest metabolomic responses reflected by the metabolic effect level index, followed by BPA and BPS. Thus, BPAF and BPS elicited higher or similar metabolism disruption compared with BPA in female zebrafish, respectively, reflecting consequences of bioconcentration.