Susceptibility to chlordecone-carbon tetrachloride induced hepatotoxicity and lethality is both age and sex dependent

The present paper examines the susceptibility to chlordecone (Kepone, CD) a nd 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 mort ality associated with CD-CCl4 interaction is highly age-dependent for both sexes. There was marked hepatotoxicity occurring in both sexes as they reac hed 45 days-of-age and females were considerably more susceptible than male s to both CD-CCl4-induced hepatotoxicity and lethality. While 63-day-old fe males are more susceptible to the CD-CCl4, interaction than their male coun terparts, the magnitude of the sex difference is diminished from that obser ved in 45-day-old rats. These findings challenge the hypothesis of Mehendal e (1990, Med. Hypotheses 33, 289-299) that chlordecone (CD) pretreatment el iminates the well-established sex difference in CCl4-treated rats. In contr ast to the CD-CCl4 findings, the sex difference in CCl4-induced hepatotoxic ity was not age-dependent and was consistent over the three ages studied. T he findings that CD-CCl4 interaction is highly age-dependent (within the 3 ages tested) but that CCl4-induced hepatot.oxicity is not, suggest that the CD-CCl4 interaction acts via a mechanism that does not primarily involve C Cl4 potentiation.