Whole-Body Disposition and Metabolism of [¹⁴C]-2,4,4'-Trichlorobiphenyl (PCB28) Following Lung Administration in Rats

Toxicities of lower-chlorinated biphenyls (LC-PCBs) have drawn increasing attention due to growing evidence of their presence in school indoor air, with 2,4,4'-trichlorobiphenyl (PCB28) being a prevalent congener. The tissue levels and characteristics of individual PCB congeners determine the PCB toxicity. Yet, the tissue disposition time course of individual LC-PCBs following pulmonary exposure is largely unknown. To address this data gap, we investigated the whole-body disposition, metabolism, and elimination kinetics of PCB28 in rats following intratracheal lung dosing of radiolabeled [¹⁴C]-PCB28. Blood, 36 tissue types, 6 digestive matters, and excreta were sampled at specific intervals (12, 25, 50, 100, 200, 400, 720, and 1440 min) postexposure. The pulmonary uptake of PCB28 was nearly complete at 99.9 ± 3.5%. PCB28 rapidly distributed across multiple tissues, initially accumulating in lung and liver, followed by redistribution to the adipose and skin. PCB28 exhibited linear toxicokinetics (TK) in highly perfused tissues, resulting in dose-proportional increases in the area under the concentration-time curves. In contrast, adipose tissue, skin, and prostate displayed nonlinear TK. The elimination half-life of [¹⁴C]-PCB28 was 12 h, with elimination primarily via the fecal route. This study provides new data on the toxicokinetics of PCB28 following pulmonary exposure to support the development of TK models for evaluating the health risks posed by this persistent environmental pollutant.