Physiologically Based Phamacokinetic (PBPK) Models for Lifetime Exposure to PCB 153 in Male and Female Harbor Porpoises (Phocoena phocoena): Model Development and Evaluation

摘要

Physiologically based pharmacokinetic (PBPK) models were developed for the most persistent polychlorinated biphenyl (PCB 153) in male and female harbor porpoises (Phocoena phocoena) to elucidate processes such as uptake, distribution, and elimination. Due to its limited metabolic capacities, long life span, and top position in marine food chains, this species is highly sensitive to pollution. The models consist of 5 compartments, liver, blubber, kidney, brain, and a compartment which accounts for the rest of the body, all connected through blood. All physiological and biochemical parameters were extracted from the literature, except for the brain/blood partition coefficient and rate of excretion, which were both fitted to data sets used for validation of the models. These data sets were compiled from our own analyses performed with GC-MS on tissue samples of harbor porpoises. The intake of PCB 153 was from milk from birth to 4 months, and after weaning fish was the main food source. Overall, these models reveal that concentrations of PCB 153 in males increase with age but suggest that as the animals grow older, metabolic transformation can be a possible pathway for elimination as well. In contrast the model for females confirms that gestation and lactation are key processes for eliminating PCB 153 as body burdens decrease with age.These PBPK models are capable of simulating the bioaccumulation of PCB 153 during the entire life span of approximately 20 years of the harbor porpoises.