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.