Abstract
•A concentration dependent increase of B[a]P metabolites was observed•No induction of phase I or II activity was observed with increasing B[a]P exposure•Biotransformation of B[a]P was successfully implemented into in silico models•The models accurately predicted life stage-specific abundances of B[a]P metabolites
Understanding internal dose metrics is integral to adequately assess effects environmental contaminants might have on aquatic wildlife, including fish. In silico toxicokinetic (TK) models are a leading approach for quantifying internal exposure metrics for fishes; however, they often do not adequately consider chemicals that are actively biotransformed and have not been validated against early-life stages (ELS) that are often considered the most sensitive to the exposure to contaminants. To address these uncertainties, TK models were parameterized for the rapidly biotransformed chemical benzo[a]pyrene (B[a]P) in embryo-larval and adult life stages of fathead minnows. Biotransformation of B[a]P was determined through measurements of in vitro clearance. Using in vitro-in vivo extrapolation, in vitro clearance was integrated into a multi-compartment TK model for adult fish and a one-compartment model for ELS. Model predictions were validated using measurements of B[a]P metabolites from in vivo flow-through exposures to graded concentrations of water-borne B[a]P. Significantly greater amounts of B[a]P metabolites were observed with exposure to greater concentrations of parent compound in both life stages. However, when assessing biotransformation capacity, no differences in phase I or phase II biotransformation were observed with greater exposures to B[a]P. Results of modelling suggested that biotransformation of B[a]P can be successfully implemented into in silico models to accurately predict life stage-specific abundances of B[a]P metabolites in either whole-body larvae or the bile of adult fish. Models developed increase the scope of applications in which TK models can be used to support environmental risk assessments.