A physiologically based pharmacokinetic model for lactational transfer of PCB 153 with or without PCB 126 in mice

Abstract

Chemical exposure via breast milk is one of the great concerns in public health. Previously, we demonstrated that most body burden of PCB 153 can be transferred from the mother to the pups in mice during lactational period. Here we present a physiologically based pharmacokinetic (PBPK) model to describe the lactational transfer of PCB 153 with or without PCB 126 in mice. The model incorporated physiological changes on the volume and the blood flow into mammary tissues, and considered mechanistic information on the movement of PCB 153 from adipose tissue to the mammary gland during lactational period. The mechanistic consideration includes fat volume changes, binding of PCB 153 to very low density lipoprotein (VLDL) and increased uptake of VLDL in mammary tissues. Model parameters depicting physiological changes were obtained from research articles dealing with chemical transfer during lactational period in rodents. Chemical-specific parameters were derived from previous PBPK models focusing on the PCB disposition in rodents. The developed model adequately described the lactational transfer of PCB 153 with or without PCB 126 in mice. Our model will provide a useful mechanistic tool to estimate the disposition of PCBs in diverse experimental designs regarding PCB effects during developmental period and to improve quantitative risk assessment of PCBs in the developing organisms.