The Risk Assessment Information System

Toxicity Profiles

CondensedToxicity Summary for HEPTACHLOR EPOXIDE

NOTE: Although the toxicity values presented in these toxicity profiles were correct at the time they were produced, these values are subject to change. Users should always refer to the Toxicity Value Database for the current toxicity values.

Prepared by: R. A. Faust, Ph.D., Chemical Hazard Evaluation Group in the Biomedical and Environmental Information Analysis Section, Health Sciences Research Division, Oak Ridge National Laboratory*.

Prepared for: Oak Ridge Reservation Environmental Restoration Program.

*Managed by Martin Marietta Energy Systems, Inc., for the U.S. Department of Energy under Contract No. DE-AC05-84OR21400.

Heptachlor epoxide, an oxidation product of the cyclodiene insecticide heptachlor, is not produced commercially in the United States and is not known to occur naturally (ATSDR 1993, IARC 1979). In the environment, heptachlor is converted to the epoxide, a chemical that degrades more slowly and, as a result, is more persistent than heptachlor. Both compounds adsorb strongly to sediments and are bioconcentrated in terrestrial and aquatic organisms; biomagnification of both is significant. Heptachlor epoxide has been identified in at least 87 of the 1300 hazardous waste sites on the EPA's National Priorities List (NPL) (ATSDR 1993).

In the body, heptachlor epoxide is formed by epoxidation of heptachlor. It is distributed to various tissues, with highest levels occurring in adipose tissues, where it may persist for prolonged periods. Heptachlor epoxide has been found in human fat, milk, and also in blood and fat of stillborn infants, indicating transplacental transfer to the fetus (IARC 1979, EPA 1986).

No studies were available regarding the toxic effects in humans after exposure to heptachlor epoxide. In laboratory animals, the liver and central nervous system are the primary target organs for heptachlor epoxide toxicity. Acute oral LD50s for rats, mice, and rabbits range from 39 to 144 mg/kg (ATSDR 1993), indicating moderate acute oral toxicity. Hypoactivity, ruffled fur, and increased mortality occurred in mice given a single oral dose of 30 mg/kg of a 25:75 heptachlor:heptachlor epoxide mixture (Arnold et al. 1977), and muscle spasms in the head and neck region and convulsive seizures were observed in young calves fed 2.5 mg/kg/day of a heptachlor epoxide preparation for 3 days (Buck et al. 1959). Increased liver weights and hepatocytomegaly were reported in male and female CD-1 mice fed a diet containing 1 to 10 ppm of a 25:75 heptachlor:heptachlor epoxide mixture for 18 months (IRDC 1973). Increased liver weights were also seen in dogs administered diets containing 0.5 to 7.5 ppm heptachlor epoxide for 60 weeks (Dow Chemical Company 1958).

An oral reference dose (RfD) of 1.3E-5 mg/kg/day for subchronic (EPA 1995a) and chronic exposure (EPA 1995b) to heptachlor epoxide was calculated based on a lowest-observed-adverse-effect level (LOAEL) of 0.0125 mg/kg/day from a 60-week dietary study with dogs (Dow Chemical Company 1958). Increased relative liver weight was identified as the critical effect. An inhalation reference concentration (RfC) for heptachlor epoxide has not been derived.

No epidemiological studies or case reports addressing the carcinogenicity of heptachlor epoxide in humans were available. Studies with laboratory animals demonstrated that heptachlor epoxide causes liver cancer in mice and rats. Liver carcinomas developed in C3H mice fed 10 ppm heptachlor epoxide for 2 years (Davis 1965). Hepatic hyperplasia, hyperplastic nodules, and liver carcinomas developed in CD-1 mice fed 0.1 to 10 ppm of a 25:75 heptachlor:heptachlor epoxide mixture for 18 months (IRDC 1973) and in CFN rats fed 0.5 to 10 ppm heptachlor epoxide for 108 weeks (Epstein 1976).

Based on EPA guidelines, heptachlor epoxide was assigned to weight-of-evidence group B2, probable human carcinogen (EPA 1995b). For oral and inhalation exposure, the slope factor is 9.1 (mg/kg/day)-1 (EPA 1995b,a). The unit risk is 2.6E-4 (µ/L)-1 for oral exposure and 2.6E-3 (µ/m3)-1 for inhalation exposure (EPA 1995b).

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Last Updated 2/13/98

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