Toxicity Profiles
Condensed Toxicity Summary for CARBON TETRACHLORIDE
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.
DECEMBER 1992
Prepared by: Andrew Francis, M.S., D.A.B.T., Chemical Hazard Evaluation and Communication Group, Biomedical Environmental Information Analysis Section, Health and Safety Research Division, *, Oak Ridge, Tennessee.
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.
Humans are sensitive to carbon tetrachloride intoxication by oral, inhalation and dermal routes. Oral and inhalation exposure to high concentrations of carbon tetrachloride results in acute central nervous system effects including dizziness, vertigo, headache, depression, confusion, incoordination and, in severe cases, respiratory failure, coma and death. Gastrointestinal problems including nausea, abdominal pain and diarrhea, often accompany these narcotic effects. Liver and kidney damage can appear after the acute symptoms subside. All symptoms can occur following a single oral or inhalation exposure. Milder narcotic effects followed by liver and kidney damage have been reported following dermal exposure. Although an inhalation exposure of about 1000 ppm for a few minutes to hours will cause the narcotic effects in 100% of the population, large variations in sensitivity are seen. Alcohol intake greatly increases human sensitivity to carbon tetrachloride; consequently, exposure to 250 ppm for 15 minutes can be life threatening to an alcoholic.
Subchronic and chronic exposure to doses as low as 10 ppm can result in liver and kidney damage (Sax and Lewis, 1989; ATSDR, 1989). Lung damage has also been reported in animals and humans but is not route specific and is believed to be secondary to kidney damage (Sax and Lewis, 1989). Prolonged exposure has been observed to cause visual effects in both humans and animals. Changes in the visual field, reduced corneal sensitivity, subnormal dark adaption, and changes in color perception have been reported in humans exposed by inhalation to a minimum concentration of 6.4 ppm, 1 hour/day for an average of 7.7 years. Increased hepatic enzyme activities indicative of liver damage have also been observed (Smyth et al., 1936; Barnes and Jones, 1967; Moeller, 1973; ATSDR, 1989).
Maternal toxicity and fetotoxic effects have been reported in rats following oral or inhalation exposure to carbon tetrachloride during gestation (Wilson, 1954; Schwetz et al., 1974). Repeated inhalation exposure of male rats to carbon tetrachloride concentrations of 200 ppm or greater has been reported to cause degeneration of the testicular germinal epithelium as well as severe liver and kidney damage (Adams et al., 1952).
A subchronic reference dose (RfDs) of 0.007 mg/kg/day has been calculated for oral exposure from a no-observed-adverse-effect level (NOAEL) of 0.71 mg/kg/day determined in a 12-week rat study (U.S. EPA, 1992a). Significantly higher doses caused minimal liver damage (Bruckner et al., 1986). A dose of 7.1 mg/kg/day was considered a lowest-observed-adverse-effect level (LOAEL). A chronic reference dose (RfDc) of 0.0007 mg/kg/day was calculated by adding an additional uncertainty factor of 10 to account for the use of a subchronic study. Confidence in the oral RfD values is rated medium by EPA (1992b).
A chronic or subchronic reference concentration (RfC) for inhalation exposure is currently under development by the EPA.
Although data for the carcinogenicity of carbon tetrachloride in humans are
inconclusive, there is ample evidence in animals that the chemical can cause liver cancer.
Hepatocellular carcinomas have been induced in hamsters, rats and mice after oral carbon
tetrachloride treatment for 16 to 76 weeks. Liver tumors have also been demonstrated in
rats following inhalation exposure, but the doses were not quantitatively established. The
EPA weight-of-evidence classification for both oral and inhalation exposure is B2, probable
human carcinogen based on adequate animal evidence. Carcinogenicity slope factors of 0.13
(mg/kg/day)-1 for oral exposure and 0.053 (mg/kg/day)-1 for inhalation exposure have been
calculated from the oral exposure experiments with hamsters, rats and mice (U.S. EPA,
1992a,b; Della Porta et al., 1961; Edwards et al., 1942; NCI, 1976a, 1976b; Weisburger, 1977).
A drinking water unit risk of 3.7 x 10-6 (µg/L)-1 and an inhalation unit risk of 1.5 x 10-5
(µg/m3)-1 have also been calculated by U.S.EPA (1992b).
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Last Updated 8/29/97