Comparative toxicology of mirex, photomirex and chlordecone after oral administration to the mouse

Abstract

AbstractThe toxicities of chlordecone (CD), mirex (M) and photomirex (PM) were compared in the male mouse after daily oral administration of 10 mg/kg in corn oil vehicle (10 ml/kg). Mortality occurred starting day 10 with M, and day 16 with PM and CD, and LT50 values were 132, 265 and 254 mg/kg, respectively. However the LT50 values of M, PM or CD were not different (range, 100–125 mg/kg) when animals were intubated with the compounds daily at 25 or 50 mg/kg. Food and water consumption and body weight were decreased after M, but PM and CD increased these parameters. Other symptoms of toxicity included severe diarrhea with M, whereas a moderate diarrhea occurred with PM and little or no diarrhea with CD. The effects of M, PM or CD on the hepatic microsomal mixed function oxidase system were compared 4 d after the administration of 10 mg/kg/d of these compounds. M and PM were equipotent, whereas CD was found to be approximately half as effective in inducing cytochrome P‐450 and associated enzyme activities. CD and M caused a decrease in blood glucose levels due to enhanced oxidation, since liver glycogen levels were also reduced. CD‐induced tremors could not be prevented by restoring the blood glucose level. CD levels in liver, muscle, whole brain and plasma were several‐fold higher than for either M or PM. These results suggest that although structurally similar, these three analogs differ significantly in their biological effects.