PT  - JOURNAL ARTICLE
AU  - H M Carpenter
AU  - L R Curtis
TI  - A characterization of chlordecone pretreatment-altered pharmacokinetics in mice.
DP  - 1989 Mar 01
TA  - Drug Metabolism and Disposition
PG  - 131--138
VI  - 17
IP  - 2
4099  - http://dmd.aspetjournals.org/content/17/2/131.short
4100  - http://dmd.aspetjournals.org/content/17/2/131.full
SO  - Drug Metab Dispos1989 Mar 01; 17
AB  - Lipophilic chlorinated hydrocarbons pose a potential health hazard to humans and animals and the toxicity of a number of these compounds has been well documented. Despite the low environmental concentrations of most of these chemicals, much of the research conducted to date has used maximally tolerated doses. Our research, conducted with low, apparently nontoxic, doses of the insecticide chlordecone (CD), showed that the administration of CD (5 mg/kg ip) to mice (C57BL/6N and DBA/2N strains) caused a time-dependent alteration in the pattern of distribution of a subsequently administered dose of [14C]CD. Livers of CD-pretreated animals contained less label than did those from controls and CD pretreatment increased amounts of label in kidney, lung, fat, and muscle. Changes did not appear to be due to an altered rate of metaboLism and analysis of total CD in tissues (unlabeled plus [14C]CD) indicated that these responses were not due to a simple redistribution phenomenon. We have termed this preexposure effect a pretreatment disposition response (PDR) and feel it may reflect an important cellular response to lipophilic compounds. CD-induced PDR is dose related, exhibits a threshold, and is saturable at a given level of induction. In addition, PDR exhibits some specificity, inasmuch as pretreating mice with CD (5 mg/kg) does not alter the distribution of subsequently administered [14C]dieldrin. The characteristics of threshold, saturability, and specificity are consistent with the premise that CD-induced PDR is a protein-mediated phenomenon.