Toxic effects, heptachlor

Death. Occupational mortality studies of pesticide workers exposed to heptachlor have not revealed an excess number of deaths in these cohorts compared to the general U.S. population. This may possibly be explained as a healthy worker effect. The ERA has described human case reports in which convulsions and death were reported following suicidal ingestion of technical-grade chlordane, which typically contains 6-30% heptachlor, but these effects cannot be attributed to heptachlor or heptachlor epoxide. There are no controlled, quantitative human data for any route of exposure. Acute lethality data were located for animals exposed via the oral and dermal routes. Both heptachlor and heptachlor epoxide may be considered very toxic via the oral route on the basis of acute animal data in rats and mice. Intermediate oral exposure to these compounds also caused up to 40% and 100% mortality in rats and mice, respectively. There appear to be differences in sensitivity in males and females in some species with the males being most sensitive. Heptachlor epoxide is more toxic than heptachlor. Heptachlor may be considered very toxic to extremely toxic via the dermal route on the basis of acute lethality data in rats and mice. The severity of acute effects may possibly depend upon the extent of formation of heptachlor epoxide and the species tested. 

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... 

This section will describe clinical practice and research concerning methods for reducing toxic effects of exposure to heptachlor and heptachlor epoxide. However, because some of the treatment discussed may be experimental and unproven, this section should not be used as a guide for treatment of exposures to heptachlor or heptachlor epoxide. When specific exposures have occurred, poison control centers and medical toxicologists should be consulted for medical advice. 

Since the metabolized form of heptachlor, heptachlor epoxide, is the most toxic, it may be possible to reduce the toxic effects of heptachlor by inhibiting the enzyme catalyzing this conversion. This is the same enzyme that catalyzes the epoxidation of aldrin to dieldrin (Gillett and Chan 1968). Further research into the specificity of this enzyme, drugs that could inhibit the enzyme, and any side effects of these drugs could help to determine the feasibility of such a treatment strategy. 

EPA is currently examining the systemic and organ toxicity of heptachlor at its Health Effects Research Laboratories in Research Triangle Park, North Carolina (NTP 1990). The testing was scheduled for completion in fiscal year 1990. 

Oral LD50 values for rats are reported at 100-220 mgkg while those for mice are 30-68 mg kg The toxic effects of heptachlor in animals are the same as those of chlordane. Chlordane toxicity in animals is similar to that of other organochlorine insecticides except tremor is absent. CNS involvement produces hyperexcitability and convulsions. 

The toxic effects of heptachlor are the same as those for chlordane. A case report of oral exposure to technical-grade chlordane reported neurological effects including irritability, salivation, dizziness, muscle tremors, and convulsions. However, exposure measurements were not provided in the report, and technical-grade chlordane contains varying amounts of heptachlor. The effects cannot be said to have resulted from exposure to heptachlor only. 

The effect of proteins on pollutant toxicity includes both quantitative and qualitative aspects. Experiments show that animals fed proteins of low biological value exhibited a lowered microsomal oxidase activity when dietary proteins were supplemented with tryptophan, the enzyme activity was enhanced. Alteration of xenobiotic metabolism by protein deprivation may lead to enhanced or decreased toxicity, depending on whether metabolites are more or less toxic than the parent compound. For example, rats fed a protein-deficient diet show decreased metabolism but increased mortality with respect to pentobarbital, parathion, malathion, DDT, and toxaphene (Table 6.4). On the other hand, rats treated under the same conditions may show a decreased mortality with respect to heptachlor, CC14, and aflatoxin. It is known that, in the liver, heptachlor is metabolized to epoxide, which is more toxic than heptachlor itself, while CC14 is metabolized to CC13, a highly reactive free radical. As for aflatoxin, the decreased mortality is due to reduced binding of its metabolites to DNA. 

The cyclodiene insecticides aldrin, dieldrin, endrin, heptachlor, endosulfan, and others were introduced in the early 1950s. They were used to control a variety of pests, parasites, and, in developing countries, certain vectors of disease such as the tsetse fly. However, some of them (e.g., dieldrin) combined high toxicity to vertebrates with marked persistence and were soon found to have serious side effects in the field, notably in Western European countries where they were extensively used. During the 1960s, severe restrictions were placed on cyclodienes so that few uses remained by the 1980s. 

No studies were located regarding death in humans after oral exposure to heptachlor or heptachlor epoxide. However, since heptachlor is a major component of the insecticide chlordane, chlordane poisoning can be considered when evaluating heptachlor toxicity data. In the case study of a woman who ingested 6 g of chlordane with suicidal intent and died 9.5 days following ingestion, no information was presented on the composition of the chlordane. Therefore, the amount of heptachlor exposure is unknown, and the effect of other components of chlordane cannot be ruled out (Derbes et al. 1955). 

In order to assess the potential extent of human exposures and health effects, members of dairy farm families who consumed raw dairy products known to be contaminated with heptachlor epoxide were studied (Stehr-Green et al. 1986). These individuals and an unexposed urban reference population were compared with regard to serum pesticide levels and liver toxicity. The farm family members had significantly higher mean serum levels of heptachlor epoxide (0.81 0.94 ppb), oxychlordane (0.70 0.75 ppb), and transnonachlor (0.79 0.60 ppb) than the unexposed population. This study is limited because exposure level, duration, and frequency of exposure are not known. There was no increase in prevalence of abnormal liver function tests in the dairy farm families... 

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. 

Reproductive Toxicity. No adverse effects on human reproduction were reported following ingestion of heptachlor-contaminated milk for 27-29 months by women of child-bearing age (Le Marchand et al. 1986). 

Weatherholtz WM, Campbell TC, Webb RE. 1969. Effect of dietary protein levels on the toxicity and metabolism of heptachlor. J Nutr 98 90-94. 

Lindane (gamma-hexachlorocyclohexane) is one of the last of the old style organochlorine pesticides still in use. Use of organochlorines such as DDT, aldrin, dieldrin, heptachlor, and toxaphene is restricted or banned in many countries because of their persistence in the environment, bioaccumulation, and toxicity. Lindane was first isolated in 1825 along with other similar compounds, but its deadly effects on insects were not recognized until the 1940s. 

Strychnine, which is detoxified by microsomal monooxygenase action, is more toxic to animals on low-protein diets, whereas octamethylpyrophosphoramide, carbon tetrachloride, and heptachlor, which are activated by monooxygenases, are less toxic. Phase II reactions may also be affected by dietary protein levels. Chloramphenicol glu-curonidation is reduced in protein-deficient guinea pigs, although no effect is seen on sulfotransferase activity in protein-deficient rats. 

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