Alteration of hepatic lipid by mirex in rats

Atsdr Evaluation of Health Effects of Chemicals

“…Decreases greater than 10% in body weight or body weight gain have been observed in a number of mirex acute-duration studies (Mehendale et al, 1973;Khera et al, 1976;Chadwick et al, 1977;Villeneuve et al, 1977;Chernoff et al, 1979a,b;Byrd et al, 1981;Ritchie and Ho, 1982;Buelke-Sam et al, 1983;Fujimori et al, 1983;Jovanovich et al, 1987;Elgin et al, 1990), intermediate-duration studies (Davison et al, 1976;Chernoff et al, 1979b;Larson et al, 1979a;Chu et al, 1981b;Fujimori et al, 1983;Curtis and Hoyt, 1984;NTP, 1990), and chronic-duration studies (NTP, 1990).…”

“…Body weight effects. Animal studies show decreases in serum glucose (Robinson and Yarbrough, 1978a;Chu et al, 1981b;Yarbrough et al, 1981;Ervin and Yarbrough, 1983;Fujimori et al, 1983;Williams and Yarbrough, 1983;Jovanovich et al, 1987) and decreases in body weight or body weight gain (Mehendale et al, 1973;Davison et al, 1976;Khera et al, 1976;Chadwick et al, 1977;Villeneuve,et al, 1977;Chernoff et al, 1979a,b;Larson et al, 1979a;Byrd et al, 1981;Chu et al, 1981a;Ritchie and Ho, 1982;Buelke-Sam et al, 1983;Fujimori et al, 1983;Curtis and Hoyt, 1984;Jovanovich et al, 1987;Elgin et al, 1990;NTP, 1990). Workers exposed to high levels of chlordecone at a facility where it was manufactured experienced an unexplained weight loss (Cannon et al, 1978), with losses of up to 60 pounds in four months in at least one individual .…”

“…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...…”

“…Several investigators have observed hepatic glycogen depletion in rats (Kendall, 1974a(Kendall, , 1979Ervin and Yarbrough, 1983;Jovanovich et al, 1987;Elgin et al, 1990) and in mice (Fujimori et al, 1983). In rats, glycogen depletion occurred after a single gavage dose as low as 100 mg/kg (Ervin and Yarbrough, 1983).…”

“…Although human data on the hepatic effects of mirex are minimal, animal studies have shown that the liver undergoes both adaptive and toxic changes following oral exposure. The primary toxic effects of mirex are inhibition of hepatobiliary excretion (Davison et al, 1976;Mehendale, 1976Mehendale, , 1977cBerman et al, 1986; Teo and Vore, 1991) and depletion of hepatic glycogen stores (Kendall, 1979;Ervin and Yarbrough, 1983;Fujimori et al, 1983;Jovanovich et al, 1987;Elgin et al, 1990). The precise mechanism for the inhibition of hepatobiliary excretion is unclear but may involve a combination of decreased uptake of substances from the blood by hepatocytes (Teo and Vore, 1990), decreased transfer of chemicals from the hepatocyte to the bile (Berman et al, 1986), and leaking from the bile duct via a paracellular pathway (Curtis and Hoyt, 1984) (see also the discussion of &dquo;Mechanisms of Action&dquo; that concludes the section &dquo;Toxicokinetics&dquo;).…”