Toxicity Profiles
Condensed Toxicity Summary for CHLOROFORM
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: Rosmarie A. Faust, Ph.D, Chemical Hazard Evaluation and Communication Group, Biomedical and 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.
Chloroform is a colorless, volatile liquid that is widely used as a general solvent and as an intermediate in the production of refrigerants, plastics, and pharmaceuticals (Torkelson and Rowe, 1976; IARC, 1976). Chloroform is rapidly absorbed from the lungs and the gastrointestinal tract, and to some extent through the skin. It is extensively metabolized in the body, with carbon dioxide as the major end product. The primary sites of metabolism are the liver and kidneys. Excretion of chloroform occurs primarily via the lungs, either as unchanged chloroform or as carbon dioxide (ATSDR, 1989).
Target organs for chloroform toxicity are the liver, kidneys, and central nervous system. Liver effects (hepatomegaly, fatty liver, and hepatitis) were observed in individuals occupationally exposed to chloroform (Bomski et al., 1967). Several subchronic and chronic studies by the oral or inhalation routes of exposure documented hepatotoxic effects in rats, mice, and dogs (Palmer et al., 1979; Munson et al., 1979; Heywood et al., 1979). Renal effects were reported in rats and mice following oral and inhalation exposures (Roe et al., 1979; Reuber, 1976; Torkelson et al., 1976), but evidence for chloroform-induced renal toxicity in humans is sparse. Chloroform is a central nervous system depressant, inducing narcosis and anesthesia at high concentrations. Lower concentrations may cause irritability, lassitude, depression, gastrointestinal symptoms, and frequent and burning urination (ATSDR, 1989).
Developmental toxicity studies with rodents indicate that inhaled and orally administered chloroform is toxic to dams and fetuses. Possible teratogenic effects were reported in rats and mice exposed to chloroform by inhalation (Schwetz et al.; 1974; Murray et al., 1979). Chloroform may cause sperm abnormalities in mice and gonadal atrophy in rats (Palmer et al, 1979; Reuber, 1979; Land et al., 1981).
A Reference Dose (RfD) of 0.01 mg/kg/day for subchronic and chronic oral exposure was calculated from a lowest-observed-adverse-effect level (LOAEL) of 15 mg/kg/day based on fatty cyst formation in the liver of dogs exposed to chloroform for 7.5 years (Heywood et al., 1979). Development of an inhalation Reference Concentration (RfC) is presently under review (U.S. EPA, 1992b).
Epidemiological studies indicate a possible relationship between exposure to chloroform present in chlorinated drinking water and cancer of the bladder, large intestine, and rectum. Chloroform is one of several contaminants present in drinking water, but it has not been identified as the sole or primary cause of the excess cancer rate (ATSDR, 1989; U.S. EPA, 1985). In animal carcinogenicity studies, positive results included increased incidences of renal epithelial tumors in male rats, hepatocellular carcinomas in male and female mice, and kidney tumors in male mice (Jorgensen et al., 1985; Roe et al., 1979; NCI, 1976).
Based on U.S. EPA guidelines, chloroform was assigned to weight-of-evidence Group
B2, probable human carcinogen, on the basis of an increased incidence of several tumor
types in rats and in three strains of mice. The carcinogen slope factor (q1*) for chloroform
is 6.1E-3 (mg/kg/day)-1 for oral exposure (U.S. EPA, 1992b) and 8.1E-2 (ug/m3)-1 for
inhalation exposure (U.S. EPA, 1992a). An inhalation unit risk of 2.3E-5 (µg/m3)-1 is based
on hepatocellular carcinomas in mice in an oral gavage study (U.S. EPA, 1992b).
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