Whole-body pharmacokinetics, maternal-placental transfer, and physiologically based modeling of inhaled 2,2’,5,5’-Tetrachlorobiphenyl (PCB52) in rats and human

Despite the ban on commercial production, restrictions, and potential toxicity of polychlorinated biphenyls (PCBs), inhalation exposure to semi-volatile PCBs that ubiquitously exist in an urban atmosphere and indoor environment remains prevalent. Semi-volatile PCBs are linked to several adverse health effects in animals and humans, including reproductive, neurological, cytotoxic, and genotoxic effects. However, the information about the lung uptake, absorption, distribution, metabolism, and excretion of individual semi-volatile PCB congeners remains unknown. Also, regulatory agencies including US United States Environmental Protection Agency call for studies investigating maternal-transfer and physiologically based pharmacokinetic (PBTK) models linking airborne PCB exposure to body burdens of specific inhaled PCB congeners in humans. Therefore, the overall objective of this work is to provide information on lung up-take, toxicokinetics, whole-body tissue disposition, placental transfer, and fetus exposure profiles of inhaled lower-chlorinated PCBs in male and pregnant rats and extrapolate the findings to humans using PBTK modeling. This study provided the missing toxicokinetic information by employing two in vivo studies and PBTK modeling in rats and scaled up to humans. Herein, we reported the toxicokinetic profiles of inhaled PCB52 in male and pregnant animals, developed a whole-body PBPK models for intravenous, oral, and intratracheal administrations. The toxicokinetic parameters derived from rat-PBPTK models were extrapolated to human toxicokinetic parameters. The multi-route PBTK model can be used to explore the toxicokinetic behaviors of structurally related compounds. My finding provided needed toxicokinetic data to conduct health risk assessments to reduce PCB exposure and associated adverse effects by public health practitioners and regulatory communities.