| Toxicokinetic and Toxicodynamic Influences on Endocrine Disruption by Polychlorinated Biphenyls Sermpan Soontornchat, Mei-Hui Li, Paul S. Cooke, and Larry G. Hansen Department of Veterinary Biosciences, University of Illinois, Urbana, IL 61801 USA Abstract
Polychlorinated biphenyl (PCB) mixtures and individual chlorobiphenyl (CB) congeners have various endocrine-disrupting effects, but ultimate responses may be altered by concurrent effects on enzyme levels and enzyme activities. The toxicodynamics of estrogenic PCBs and metabolites have been studied in vitro, but nonlinear dose-response relationships in vivo suggest that tests must integrate toxicokinetic parameters to explain whole-animal responses. To determine if any such interactions occurred, relatively large doses were subdivided into different treatment regimens for immature female Sprague-Dawley rats. Aroclor 1242 was uterotropic when 120 mg/kg (total) was administered (intraperitoneally) in two, three or five doses. CB 47 (2,2´,4,4´-tetraCB) and CB 153 (2,2´,4,4´,5,5´-hexaCB) increased absolute uterine weights at 30 mg/kg on days 20 and 21. Results at 25 days in rats that received zero, two, three or five doses between days 20 and 24 were much more variable due to changes in tissue responsiveness and/or toxicokinetic interactions. In rats receiving treatment for 5 days, pentoxyresorufin O-dealkylase (PROD) activity was inversely related to CB serum residues ; in rats receiving CB 153 for 2 days, PROD activity was directly related to serum residues. It was not clear whether PROD activity was the cause of or a reflection of lower serum residues ; however, nonplanar CBs are better substrates for PROD than are planar CBs, and the longer-term dosing may enhance metabolism and excretion, changing the biological effects observed. Key words: chlorobiphenyl, estrogenicity, pentoxyresorufin O-dealkylase, polychlorinated biphenyl, toxicodynamics, toxicokinetics. Environ Health Perspect 102:568-571 (1994) http://ehpnet1.niehs.nih.gov/docs/1994/102-6-7/soontornchat.html
Address correspondence to L.G. Hansen, Department of Veterinary Biosciences, University of Illinois, 2001 S. Lincoln Avenue, Urbana, IL 61801 USA. S. Soontornchat was supported by a fellowship from the Royal Thai Embassy, and M-H. Li was supported in part by the Environmental Toxicology Scholars Program, Institute for Environmental Studies, University of Illinois. We gratefully acknowledge the assistance of Yi-Dong Zhao and Carrie Rhine. David Schaeffer provided considerable statistical assistance during the manuscript revision. Received 8 February 1994 ; accepted 21 April 1994.
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