Hepatitis heptachlor

No studies were located regarding respiratory, gastrointestinal, musculoskeletal, hepatic, renal, or dermal/ocular effects in humans or animals after inhalation exposure to heptachlor or heptachlor epoxide. 

There are data from animal studies in mice, rats, and pigs that indicate that both carbohydrate metabolism and lipid metabolism may be affected by exposure to heptachlor or heptachlor epoxide (Enan et al. 1982 Halacka et al. 1974 Kacew and Singhal 1973 Pelikan 1971). Alterations in gluconeogenic enzymes and an increase in cellular steatosis in the liver have been reported. Granulomas and fibrotic liver have also been observed. In addition, hepatocellular carcinoma was identified as causally related to heptachlor in the diet in a mouse study conducted by the National Cancer Institute (NCI 1977). The existing evidence suggests that heptachlor and heptachlor epoxide are hepatic toxicants. 

Other work has indicated that chlordane and heptachlor are energy transfer inhibitors as evidenced by marked decreases in oxidative phosphorylation of rat hepatic mitochondria following in vitro incubation of the mitochondria with the pesticides (Ogata et al. 1989). Interestingly, even though heptachlor epoxide is more toxic than either chlordane or heptachlor in tests of general toxicity, it was less effective in inhibiting mitochondrial respiration. 

Although there are no data from human studies that indicate that hepatic effects occur in humans exposed to heptachlor, the animal studies indicate that the liver is a target organ for this chemical and is more sensitive to low doses than the neurological system. Decreased glycogen, increased cholesterol, GOT, and AP enzyme levels, and increased liver weight were reported in mice fed heptachlor at 0.5 mg/kg/day. In contrast, neurological effects such as convulsions were observed in a cow fed 2.5 mg/kg/day heptachlor daily for 15 days (Buck et al. 1959). Increased liver enzymes could indicate exposure to heptachlor, but this would not be a marker specific to this chemical. Refer to Section 2.2 for a detailed discussion of the effects caused by heptachlor and heptachlor epoxide. 

Nutritional factors may influence the toxicity of pesticides. Research in this area has primarily focused on the role of dietary proteins, particularly sulfur-containing amino acids, trace minerals, and vitamins A, C, D, and E. Studies in rats show that inadequate dietary protein enhances the toxicity of most pesticides but decreases, or fails to affect, the toxicity of a few. The results of these studies have shown that at one-seventh or less normal dietary protein, the hepatic toxicity of heptachlor is diminished as evidenced by fewer enzyme changes (Boyd 1969 Shakman 1974). The lower-protein diets may decrease metabolism of heptachlor to heptachlor epoxide. 

Walter Reed-Wistar and Charles River male adult rats were exposed to oral doses of turpentine or to turpentine vapors, which consisted of a- and p-pinene. These exposures were followed by oral administration of heptachlor epoxide or of one of three pesticides, paraoxon, heptachlor, or parathion, or by an intraperitoneal injection of hexobarbital. The studies revealed that pretreatment with turpentine reduced hexobarbital sleeping time, reduced the parathion LDso, and increased the heptachlor LDso. The paraoxon and heptachlor epoxide LOo values were unchanged. a-Pinene and P-pinene vaporized from turpentine had no effect on either hexobarbital sleeping time or parathion, paraoxon, or heptachlor epoxide mortality but did increase the heptachlor LDso (Sperling et al. 1972). The authors speculated that increases in hepatic microsomal enzyme activity are responsible for these differences. 

No studies were located indicating that any populations are unusually susceptible to heptachlor or heptachlor epoxide. There is a possibility that very young children may exhibit particular susceptibility to hepatic effects because of the immaturity of the hepatic microsomal system. Heptachlor is bioactivated to produce heptachlor epoxide which is more toxic than heptachlor. Preadolescent children have a greater rate of glutathione turnover, and they are expected to be more susceptible to heptachlor epoxide-induced toxicity. Their susceptibility would probably depend upon their ability to detoxify heptachlor epoxide. Individuals who show reduced liver function for other... 

Kacew S, Singhal RL. 1973. The influence of p,p-DDT, a-chlordane, heptachlor, and endrin on hepatic and renal carbohydrate metabolism and cyclic AMP-adenyl cyclase system. Life Sci 13 1363-1371. 

Heptachlor epoxide is more toxic then heptachlor. The acute oral LD50 for heptachlor epoxide in rodents and rabbits ranged from 39 to 144mg/kg3 After dietary exposure of rats, heptachlor epoxide caused hepatic cell vacuolization at all dose levels (0.5-10 ppm for up to 108 weeks). Degeneration, hepatomegaly, and regeneration were also reported. Like heptachlor, the ability of heptachlor epoxide to induce lethality after acute exposure may involve its ability to interfere with nerve action or release of neurotransmitters and to inhibit the function of the receptor for y-aminobutyric acid. ... 

Daily oral administrations of 2 or 5 mg kg body weight heptachlor for 78-86 days to pigs, sheep, and rats induced hepatic necrosis. Results of animal tests show that chronic exposure to heptachlor or its epoxide metabolite adversely affects the liver, kidney, and red blood cells. There is evidence that heptachlor and heptachlor epoxide are associated with infertility and improper development of offspring. Animal studies have shown that females were less likely to become pregnant when both males and females were fed heptachlor. The incidence of liver carcinomas increased in rats receiving doses of approximately 1.2 mg kg day of either heptachlor or heptachlor epoxide. 

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