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

Yau Adamu; Nicole Marie Brandon; Andrea Adamcakova-Dodd; Hui Wang; Peter S Thorne

doi:10.1021/acs.est.5c07982

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

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

Yau Adamu, Nicole Marie Brandon, Andrea Adamcakova-Dodd, Hui Wang and Peter S Thorne

Environmental science & technology, Vol.59(43), pp.23106-23124

11/04/2025

DOI: 10.1021/acs.est.5c07982

PMCID: PMC12593371

PMID: 41130726

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Abstract

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 [ C]-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 [ C]-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.

forever chemicals

pulmonary

toxicokinetics

PCB28

polychlorinated biphenyl

ADME

UIOWA OA Agreement

Details

Title: Subtitle: Whole-Body Disposition and Metabolism of [ 14 C]-2,4,4'-Trichlorobiphenyl (PCB28) Following Lung Administration in Rats
Creators: Yau Adamu - University of Iowa
Nicole Marie Brandon - University of Iowa
Andrea Adamcakova-Dodd - University of Iowa
Hui Wang - University of Iowa
Peter S Thorne - University of Iowa
Resource Type: Journal article
Publication Details: Environmental science & technology, Vol.59(43), pp.23106-23124
DOI: 10.1021/acs.est.5c07982
PMID: 41130726
PMCID: PMC12593371
NLM abbreviation: Environ Sci Technol
ISSN: 0013-936X
eISSN: 1520-5851
Publisher: American Chemical Society; WASHINGTON
Grant note: National Institute of Environmental Health SciencesSimulations Plus, Inc. under their SLP University+ Program
The ADMET Predictor software access was provided graciously by Simulations Plus, Inc. under their SLP University+ Program. The authors acknowledge Dr. Guohua An of the University of Iowa College of Pharmacy for assistance with the Phoenix PBTK software.
Language: English
Electronic publication date: 10/23/2025
Date published: 11/04/2025
Academic Unit: Civil and Environmental Engineering; Occupational and Environmental Health; Iowa Superfund Research Program
Record Identifier: 9985019031302771

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