The Risk Assessment Information System

Toxicity Profiles

Condensed Toxicity Summary for METHYLENE CHLORIDE

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.

September 1993

Prepared by Cheryl B. Bast, Ph.D., Chemical Hazard Evaluation and Communication Program, Biomedical and Environmental Information Analysis Section, Health Sciences Research Division, *, Oak Ridge, Tennessee.


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

Methylene chloride (CH2Cl2, CAS No. 75-09-2), also known as dichloromethane is a colorless volatile liquid with a penetrating ether-like odor. In industry, methylene chloride is widely used as a solvent in paint removers, degreasing agents, and aerosol propellants; as a polyurethane foam-blowing agent; and as a process solvent in the pharmaceutical industry. The compound is also used as an extraction solvent for spice oleoresins, hops, and caffeine (ATSDR, 1989; IARC, 1986).

Methylene chloride is readily absorbed from the lungs, the gastrointestinal tract, and to some extent through the skin. Metabolism of methylene chloride produces CO2 and CO, which readily binds with blood hemoglobin to form carboxyhemoglobin (CO-Hb). The primary adverse health effects associated with methylene chloride exposure are central nervous system (CNS) depression and mild liver effects. Neurological symptoms described in individuals occupationally exposed to methylene chloride included headaches, dizziness, nausea, memory loss, paresthesia, tingling hands and feet, and loss of consciousness (Welch, 1987). Major effects following acute inhalation exposure include fatigue, irritability, analgesia, narcosis, and death (ATSDR, 1989). CNS effects have also been demonstrated in animals following acute exposure to methylene chloride (Weinstein et al., 1972; Berger and Fodor, 1968).

Impaired liver function has been associated with occupational exposure to methylene chloride (Welch, 1987). Liver effects have also been documented in a number of inhalation studies with laboratory animals. Subchronic exposure of rats, mice, dogs, and monkeys caused mild hepatic effects such as cytoplasmic vacuolization and fatty changes (U.S. EPA, 1983; Haun et al., 1972; Weinstein and Diamond, 1972; Heppel, 1944). Hepatocellular foci, fatty changes, and necrosis were reported following chronic inhalation exposure of rats and mice (Nitschke et al., 1986a; NTP, 1986). Chronic oral exposure to methylene chloride via drinking water resulted in histopathological alterations of the liver in rats and mice (NCA, 1982, 1983). In addition, inhalation exposure of rats caused nonspecific degenerative and regenerative changes in the kidneys (U.S. EPA, 1983; Haun et al., 1972).

A subchronic and chronic oral reference dose (RfD) of 6E-2 mg/kg/day for methylene chloride has been calculated by U.S. EPA (1993a,b). This value is based on a NOAEL of 5.85 mg/kg/day derived from a chronic drinking water study with rats (NCA, 1982). This same study was adapted for the derivation of the subchronic and chronic reference concentration (RfC) of 3E+0 mg/m3 (NOAEL, 694.8 mg/m3) (U.S. EPA, 1993a).

Studies of workers exposed to methylene chloride have not recorded a significant increase in cancer cases above the number of cases expected for nonexposed workers (Hearne et al., 1987; Ott et al., 1983a; Friedlander et al., 1978). However, long-term inhalation studies with rats and mice demonstrated that methylene chloride causes cancer in laboratory animals. Mice exposed via inhalation to high concentrations of methylene chloride (2000 or 4000 ppm) exhibited a significant increase of malignant liver and lung tumors compared with nonexposed controls (NTP, 1986). Rats of both sexes exposed to concentrations of methylene chloride ranging from 500 to 4000 ppm showed increases of benign mammary tumors (Nitschke et al., 1988a; NTP, 1986; Burek et al., 1984). An inhalation study with rats and hamsters revealed sarcomas of the salivary gland in male rats, but not in female rats or hamsters (Burek et al., 1984). Liver tumors observed in rats and mice that ingested methylene chloride in drinking water for 2 years provided suggestive evidence of carcinogenicity (NCA, 1982, 1983). Based on inadequate evidence of carcinogenicity in humans and on sufficient evidence in animals, U.S. EPA (1993b) has placed methylene chloride in weight-of-evidence group B2, probable human carcinogen. A slope factor and unit risk of 7.5E-3 (mg/kg/day)-1 and 2.1E-7 (ug/L)-1, respectively, (U.S. EPA, 1993b) was derived for oral exposure to methylene chloride. The inhalation unit risk is 4.7E-7 (ug/m3)-1 (U.S. EPA, 1993b). Retrieve Toxicity Profiles Formal Version

Last Updated 10/31/97

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