Dichloromethane is used principally as a solvent, in paint removers, degreasers and aerosol products, and in the manufacture of foam polymers. Widespread exposure occurs during the production and industrial use of dichloromethane and during the use of a variety of consumer products containing dichloromethane. Substantial losses to the environment lead to ubiquitous low-level exposures from ambient air and water.
5.2 Human carcinogenicity data
Seven cohort studies have examined the risk of cancer among populations exposed to dichloromethane. Two studies observed an excess of pancreatic cancer, but the three others which reported on this tumour did not. One study observed an excess of liver and biliary tract cancers among longer-term employees. One study observed an excess of prostate cancer that appeared to increase with level of exposure. One study observed an excess of breast cancer and gynaecological cancers among women with the highest likelihood of exposure and another study observed an excess of cervical cancer. With the exception of the prostate cancer excess observed in one study, all the excesses were based on small numbers. No estimates of exposure levels were available for two of the six studies.
Three case–control studies have examined the risk of cancer associated with dichloromethane exposure and provided data adequate for evaluation. One observed an association between estimated intensity, probability and duration of exposure and the risk of astrocytic brain tumours. A second, which focused on female breast cancer, observed an elevated risk in the highest exposure category but no association with probability of exposure. The third indicated an increased risk of rectal cancer and possibly lung cancer.
For no type of cancer was there a sufficiently consistent elevation of risk across studies to make a causal interpretation credible.
5.3 Animal carcinogenicity data
Dichloromethane was tested by oral administration in the drinking-water in one study in mice and one study in rats, by inhalation exposure in two studies in mice, three studies in rats and one study in hamsters and by intraperitoneal injection in a lung adenoma assay in mice. In the study in mice by oral administration, no increase in tumour incidence was observed. The study in rats by oral administration gave inconclusive results. In the two inhalation studies in mice, increased incidences of benign and malignant lung and liver tumours were observed in both sexes. In the three inhalation studies in rats, the incidence of benign mammary tumours was increased in one study in females of a strain in which the incidence of spontaneous mammary tumours is low, and the multiplicity was increased in two studies in females of a high-incidence strain. In one study, in males, the incidence of mammary gland adenomas and fibroadenomas was increased. Negative results were obtained in the lung adenoma test in mice and in the inhalation study in hamsters.
5.4 Other relevant data
Two dose-dependent alternative pathways involving cytochrome P450 and glutathione S-transferases are responsible for the metabolism of dichloromethane in human and rodent cells.
Dichloromethane is consistently mutagenic in microorganisms. Weaker and less consistent responses are seen in mammalian systems, predominantly in mice, both in vitro and in vivo.
It induced sister chromatid exchanges, chromosome breakage and chromosome loss in vitro in human cells. In-vitro results in rodent cells were inconclusive or negative.
Dichloromethane induced DNA single-strand breaks in mammalian cell cultures, but inconclusive or negative effects were reported for induction of gene mutations. It did not induce unscheduled DNA synthesis either in vivo in rodents or in human fibroblast cultures. It was genotoxic in fungi but not in Drosophila in the sex-linked recessive lethal assay.
Mechanistic studies have established a link between glutathione S-transferase-mediated metabolism of dichloromethane and its genotoxicity and carcinogenicity in mice. The glutathione S-transferase responsible for the metabolism of dichloromethane is expressed to significantly greater extents in mouse tissues than in rat, hamster or human tissues.
The available data suggest a plausible mechanism for the development of liver and lung tumours which occur in mice but not in rats exposed to dichloromethane.
5.5 Evaluation
There is inadequate evidence in humans for the carcinogenicity of dichloromethane.
There is sufficient evidence in experimental animals for the carcinogenicity of dichloromethane.
Overall evaluation
Dichloromethane is possibly carcinogenic to humans (Group 2B).
Previous evaluations: Vol. 20 (1979); Vol. 41 (1986); Suppl. 7 (1987)
Synonyms
See Also:
Toxicological Abbreviations
Dichloromethane (ICSC)
Dichloromethane (FAO Nutrition Meetings Report Series 48a)
Dichloromethane (WHO Food Additives Series 30)
DICHLOROMETHANE (JECFA Evaluation)