Uterotropic and enzyme induction effects of 2,2{prime},5-trichlorobiphenyl
- Univ. of Illinois, Urbana, IL (United States)
Polychlorinated biphenyls (PCBs) are among the ubiquitously persistent chemicals possessing endocrine-disrupting effects. Most of the environmentally abundant CB congeners have one or more ortho chlorines in the biphenyl ring. Because ortho-chlorinated CB congeners do not avidly bind to the aryl hydrocarbon (Ah) receptor, this clearly suggests that the estrogenicity of PCBs is not related to potency as Ah receptor agonists. It is important to investigate the estrogenicity of those ortho-chlorinated CB congeners in order to more accurately predict the hazards from PCB residues in the environment. The hydroxylated metabolites are presumably more reactive with the estrogen receptor, but induction of phase 2 enzymes at the higher doses could sequester the metabolites resulting in the lower serum residues of parent compound and attenuated estrogenic activity observed at higher doses. It was of interest to determine if a di-ortho CB congener which is more readily metabolized and an ineffective PROD inducer exhibited similar nonlinear dose:response relationships for estrogenicity and serum residues as observed for CB 153. CB 18 (2,2{prime}, 5-trichlorobiphenyl) is very rapidly metabolized to more polar products by sheep liver microsomes, rats and house flies. The detection of greater amounts of mono-hydroxylated metabolites from slower metabolized congeners than from CB 18 reflects further secondary metabolism in these extended (up to 1 hour) microsomal incubations. Such secondary metabolism should be relatively constant up to very high doses in vivo, since CB 18 should be a very poor P450 2B1 inducer. Even though CB 18 commonly occurs in environmental samples, there is little information regarding its biological effects. In this study, we used immature Sprague-Dawley female rats as an animal model to examine the uterotropic response, thyrotoxic effect and enzyme induction potency of CB 18. 17 refs., 3 tab.
- OSTI ID:
- 61813
- Journal Information:
- Bulletin of Environmental Contamination and Toxicology, Vol. 54, Issue 4; Other Information: PBD: Apr 1995
- Country of Publication:
- United States
- Language:
- English
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