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, a cyclodiene insecticide, was extensively used until the 1970s for the control of a variety of insects. At the present time, its only permitted commercial use in the United States is fire ant control in power transformers. Heptachlor is converted to heptachlor epoxide and other degradation products in the environment. The epoxide degrades more slowly and, as a result, is more persistent than heptachlor. Both heptachlor and heptachlor epoxide are bioconcentrated in terrestrial and aquatic organisms. Heptachlor is subject to long-range transport and removal from the atmosphere by wet deposition (ATSDR 1993, Leber and Benya 1994).
Heptachlor is absorbed from the gastrointestinal tract, lungs, and skin. It is distributed to various tissues, with highest levels occurring in adipose tissue. Transplacental transfer to the fetus has been reported (EPA 1986). Metabolism produces primarily heptachlor epoxide, which is more toxic than its parent compound. Heptachlor and its metabolites are eliminated primarily via feces (Tashiro and Matsumara 1978).
The primary adverse health effects associated with heptachlor are central nervous system and liver effects. For humans, acute oral exposure has resulted in abnormal behavior, hyperirritability, tremors, and convulsions (Leber and Benya 1994). Various central nervous system effects such as hyperexcitability, incoordination, tremors, muscle spasms, and seizures have also been reported in animals following acute and subchronic oral exposure (Akay and Alp 1981, Buck et al. 1959, EPA 1985). Oral LD50 values for rabbits, rats, sheep, and calves are 2000, 90 to 160, 50, and 20 mg/kg, respectively (IARC 1979, Leber and Benya 1994). Although hepatic effects have not been reported in humans, chronic dietary exposure of rodents to 10 ppm heptachlor or to 10 ppm of a 25:75 mixture of heptachlor/heptachlor epoxide for 18 months has produced increased liver weights, liver lesions, and decreased body weight gains (Velsicol Chemical Corporation 1955, IRDC 1973).
Other effects reported in humans include blood dyscrasias as a result of exposure to heptachlor during home termite treatment (Epstein and Ozonoff 1987) and increased mortality from cerebrovascular disease in workers manufacturing pesticides. However, cardiovascular effects were not seen in a cohort of pesticide applicators with potentially high exposures to heptachlor (Wang and MacMahon 1979a,b). Reduced fertility, increased resorptions, and decreased survival of offspring was noted in rats fed diets containing 0.25 mg/kg/day for 60 days prior to mating, with treatment continuing through gestation for the females (Green 1970). Reduced fertility and an increased incidence of cataracts, particularly in offspring, was reported in rats fed 6 mg/kg/day over a an 18-month period (Mestitzova 1967).
An oral reference dose (RfD) of 5E-4 mg/kg/day for subchronic (EPA 1995a) and chronic exposure (EPA 1995b) to heptachlor was calculated based on a no-observed-adverse-effect level (NOAEL) of 0.15 mg/kg/day and a lowest-observed-adverse-effect level (LOAEL) of 0.25 mg/kg/day from a 2-year dietary study with rats (Velsicol Chemical Corporation 1955). Increased relative liver weight was identified as the critical effect. An inhalation reference concentration (RfC) for heptachlor has not been derived.
Existing epidemiological studies on heptachlor are inadequate to establish a clear assessment of heptachlor exposure and human risk of developing cancer. Large-scale occupational cohort studies on workers engaged in the manufacture of heptachlor and pesticide applicators have not identified significantly increased cancer deaths (Wang and McMahon 1979a,b). Several bioassays have shown that heptachlor can cause liver cancer in mice. Bioassays with rats were generally negative. Benign liver tumors and hepatocellular carcinomas developed in both sexes of C3H mice fed 10 ppm heptachlor for 2 years; hepatocellular carcinomas developed in both sexes of B6C3F1 mice fed 6-18 ppm technical grade heptachlor for 80 weeks; and nodular hyperplasia benign hepatomas and hepatocellular carcinomas developed in CD-1 mice fed 5 ppm (both sexes) or 10 ppm (males) of a 25:75 heptachlor/heptachlor epoxide mixture for 18 months (Epstein 1976, NCI 1977).
Based on EPA guidelines, heptachlor was assigned to weight-of-evidence group B2, probable human carcinogen. For oral exposure, the slope factor is 4.5 (mg/kg/day)-1 and the unit risk is 1.3E-4 (µg/L)-1 (EPA 1995b). The inhalation slope factor and unit risk are 4.5 (mg/kg/day)-1 (EPA 1995a) and 1.3E-3 (µg/m3)-1 (EPA 1995b), respectively.Retrieve Toxicity Profiles Formal Version
Last Updated 2/13/98