title: Susceptibility to chlordecone-carbon tetrachloride induced hepatotoxicity and lethality is both age and sex dependent.
abstract: The present paper examines the susceptibility to chlordecone (Kepone, CD) and carbon tetrachloride across different ages (35, 45, and 63-days-old) in male and female Sprague-Dawley rats using different lengths of time on a CD diet (10 ppm). The principal findings are that the hepatotoxicity and mortality associated with CD-CCl4 interaction is highly age-dependent for both sexes. There was marked hepatotoxicity occurring in both sexes as they reached 45 days-of-age and females were considerably more susceptible than males to both CD-CCl4-induced hepatotoxicity and lethality. While 63-day-old females are more susceptible to the CD-CCl4 interaction than their male counterparts, the magnitude of the sex difference is diminished from that observed in 45-day-old rats. These findings challenge the hypothesis of Mehendale (1990, Med. Hypotheses 33, 289-299) that chlordecone (CD) pretreatment eliminates the well-established sex difference in CCl4-treated rats. In contrast to the CD-CCl4 findings, the sex difference in CCl4-induced hepatotoxicity was not age-dependent and was consistent over the three ages studied. The findings that CD-CCl4 interaction is highly age-dependent (within the 3 ages tested) but that CCl4-induced hepatotoxicity is not, suggest that the CD-CCl4 interaction acts via a mechanism that does not primarily involve CCl4 potentiation.
authors.affiliation: Northeast Regional Environmental Public Health Center, University of Massachusetts, Amherst 01003, USA.
authors.forename: R B
authors.initials: RB
authors.lastname: Blain
authors.forename: R
authors.initials: R
authors.lastname: Reeves
authors.forename: K A
authors.initials: KA
authors.lastname: Ewald
authors.forename: D
authors.initials: D
authors.lastname: Leonard
authors.forename: E J
authors.initials: EJ
authors.lastname: Calabrese
mesh_terms: D000367:Age Factors; D000410:Alanine Transaminase / Q000378:metabolism; D000818:Animals; D001219:Aspartate Aminotransferases / Q000378:metabolism; D002251:Carbon Tetrachloride / Q000633:toxicity*; D056486:Chemical and Drug Induced Liver Injury; D007631:Chlordecone / Q000633:toxicity*; D004347:Drug Interactions; D005260:Female; D007306:Insecticides / Q000633:toxicity*; D008099:Liver / Q000187:drug effects / Q000201:enzymology*; D008107:Liver Diseases / Q000235:genetics / Q000401:mortality / Q000473:pathology; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D012737:Sex Factors; D015996:Survival Rate; D013997:Time Factors
chemical_list: D007306:Insecticides; D002251:Carbon Tetrachloride; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D007631:Chlordecone