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

Abstract

The 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.

Atsdr Evaluation of Health Effects of Chemicals

“…Severe diarrhea was reported in mice following gastric intubation with mirex for up to 15 days, but the report did not state which of the doses (10, 25, or 50 mg/kg/day) caused this effect. Necropsy showed hemorrhagic intestines, indicating a gastrointestinal origin for the diarrhea rather than a neurally mediated response (Fujimori et al, 1983). Mild diarrhea also has been observed in a 33-day gavage study in mice exposed to 10 mg/kg/day of chlordecone.…”

“…Mild diarrhea also has been observed in a 33-day gavage study in mice exposed to 10 mg/kg/day of chlordecone. No effects were reported, however, on stomach or intestines at necropsy (Fujimori et al, 1983). Likewise, routine histopathological analyses of gastrointestinal tissues also showed no compound-related effects in rats after two years of exposure at 1.25 mg/kg/day or in dogs after 124-128 weeks of exposure at 0.625 mg/kg/day (Larson et al, 1979b).…”

“…Male rats showed approximately 5% mortality at 6 mg/kg/day for ten days (Khera et al, 1976). Male mice had higher mortality with 80% mortality, following 14 daily doses of 10 mg/kg/day (Fujimori et al, 1983). …”

“…In mice of both sexes, at a dose of 7.8 mg/kg/day for up to 12 months, only one of eight adult mice died whereas four of four juvenile mice died, indicating a greater sensitivity in immature mice (Huber, 1965). At 10 mg/kg/day, all male mice died by day 33 of dosing (Fujimori et al, 1983). Survival was decreased in female rats at 1.25 mg/kg/day in a two-year feeding study (Larson et al, 1979b) and in both male and female rats at 1.2-1.3 mg/kg/day in an 80-week feeding study (NCI, 1976).…”

“…The adaptive effects observed are those generally produced by halogenated hydrocarbons; these include increase in liver weight or size (Gaines and Kimbrough, 1970;Mehendale et al, 1973;Abston and Yarbrough, 1976;Davison et al, 1976;Chadwick et al, 1977;Fulfs et al, 1977;Villeneuve et al, 1977;Robinson and Yarbrough, 1978a,c;Warren et al, 1978;Hewitt et al, 1979;Larson et al, 1979a;Pittz et al, 1979;Chu et al, 1980bChu et al, , 1981aMehendale, 1981b;Robacker et al, 1981;Yarbrough et al, 1981Yarbrough et al, , 1984Yarbrough et al, , 1986aYarbrough et al, ,b, 1992Ritchie and Ho, 1982;Chambers and Trevethan, 1983;Ervin and Yarbrough, 1983;Fujimori et al, 1983;Williams and Yarbrough, 1983;Curtis and Hoyt, 1984;Karl and Yarbrough, 1984;Jovanovich et al, 1987;Plaa et al, 1987;Purushotham et al, 1988;Wilson and Yarbrough, 1988;Elgin et al, 1990;Teo and Vore, 1991;Thottassery and Yarbrough, 1991 ). Other effects observed include hepatocellular hypertrophy (Gaines and Kimbrough, 1970;Davison et al, 1976;Fulfs et al, 1977;Ulland et al, 1977a;Yarbrough et al, 1981), cytopla...…”