Owing to their limitations, the available epidemiological data are considered inadequate to assess the carcinogenicity of dichloromethane in humans.

The potential carcinogenicity of dichloromethane in occupationally exposed populations has been investigated in several epidemiological studies, the most extensive of which was that of a cohort of dichloromethane-exposed male workers from the Eastman Kodak company in Rochester (Hearne et al., 1990). Based on comparison of rates in a cohort to those of both the general population and an industrial referent group, there were nonsignificant deficits in observed:expected ratios for lung cancer, liver cancer and ischemic heart disease. Deaths from other malignant neoplasms were lower (non-significant) than expected, based upon the two control populations.

In an historical cohort study of workers at a fibre manufacturing plant in Rock Hill, South Carolina, excess mortality in comparison with local rates was reported for the buccal cavity and pharynx, liver and biliary passages and melanoma (Ott et al., 1983a,b; Lanes et al., 1990). However, the numbers of observed cases were extremely small and workers were exposed to other substances. Mortality in the cohort may also have been underestimated.

Based upon an historical cohort study at a Dow Chemical manufacturing site in Louisiana, there was no excess mortality overall or due to cancer in workers exposed to dichloromethane and numerous other chemicals, though the power to detect such increases was low (Olsen et al., 1989).

In a case-control study in a chemical production facility, there was no association between exposure to dichloromethane when 44 cases of liver and biliary tract cancer were compared to 1888 referents randomly selected from a cohort of 21,437 workers (Bond et al., 1990).

In studies in which two strains of mice (Swiss, B6C3F1) were exposed by gavage to doses of up to 500 mg/kg bw/day for up to 78 weeks, there was a significant increase in lung tumours in the former strain, while only a slight increase in small lung masses in females was observed in the latter strain (Maltoni et al., 1986, 1988; Serota et al., 1986a). In Sprague-Dawley rats exposed to up to 500 mg/kg bw/day by stomach tube for 64 weeks (Maltoni et al., 1986, 1988), there was a nonsignificant increase in malignant mammary tumours. Tumour incidence in F344 rats exposed to up to 250 mg/kg bw/day dichloromethane in drinking water for two years was equivocal (Serota et al., 1986b).

The lowest reported effect level for non-neoplastic effects in adequately documented investigations following chronic exposure by ingestion (drinking water) of dichloromethane is 50 mg/kg bw/day in F344 rats. At this dose, fully reversible cellular proliferation and partially reversible fatty change in the livers were observed [lowest observed effect level (LOEL)=50 mg/kg bw/day; NOEL=5 mg/kg bw/day] (Serota et al., 1986b).

Only one chronic inhalation study has been conducted in mice (NTP, 1986; Mennear et al., 1988). In this bioassay, male and female B6C3F1 mice were exposed to 0, 2000 or 4000 ppm (0, 6940 or 13, 880 mg/cu.m) dichloromethane in air for 102 weeks. It was concluded that there was "clear evidence of carcinogenicity of dichloromethane for male and female B6C3F1 mice, as shown by increased incidences of alveolar/bronchiolar neoplasms and of hepatocellular neoplasms" (NTP, 1986).

In the most extensive inhalation bioassays in experimental animals exposed to dichloromethane conducted to date, there have been increases in the incidence of benign and malignant tumors in the lungs of both male and female mice, benign (females only) and malignant tumors in the liver (both male and female) of mice and benign mammary tumors in male and female rats. There has also been a borderline increase in malignant liver tumours in female rats. Dichloromethane has been mutagenic in vitro and genotoxic in some studies in vivo. Therefore, dichloromethane has been classified as "probably carcinogenic to humans" (Group II). It is recognized, however, that there are clear species differences in the putatively carcinogenic pathway of metabolism of dichloromethane which are consistent with the hypothesis that humans are likely to be less sensitive than some species of experimental animals in this regard.

The Health Canada supporting documentation and assessment were approved by an interdirectorate committee of the Health Protection Branch of Health Canada and externally reviewed by Dr. A.G. Renwick of the University of Southampton, Dr. R.J. Bull of Washington State University and staff of the Information Department of BIBRA Toxicology International. Dr. L. Rhomberg of the U.S. Environmental Protection Agency, Dr. K. Khanna of the University of Montreal and Dr. R.H. Reitz of Dow Chemical reviewed the physiologically based pharmacokinetic modeling. The supporting documentation was externally reviewed by Dr. T. Green, ICI Central Toxicology Laboratory.

Data identified prior to March 1993 were considered for inclusion in the Health Canada assessment.

Bond, G.G., E.A. McLaren, F.L. Sabel, K.M. Bodner, T.E. Lipps and R.R. Cook. 1990. Liver and biliary tract cancer among chemical workers. Am. J. Ind. Med. 18(1), 19-24. In: MRI (1991).

Hearne, F.T., J.W. Pifer and F. Grose. 1990. Absence of adverse mortality effects in workers exposed to methylene chloride: an update. J. Occup. Med. 32(3), 234-240.

Lanes, S.F., A. Cohen, K.J. Rothman, N.A. Dreyer and K.J. Soden. 1990. Mortality of cellulose fiber production workers. Scand. J. Work Environ. Health 16(4), 247-251.

Maltoni, C., G. Cotti and G. Perino. 1986. Experimental Research on Methylene Chloride Carcinogenesis. Archives of Research on Industrial Carcinogenesis, Volume IV. C. Maltoni and M.A. Mehlman, series editors. Princeton Scientific Publishing. 244 p.

Maltoni, C., G. Cotti and G. Perino. 1988. Long-term carcinogenicity bioassays on methylene chloride administered by ingestion to Sprague-Dawley rats and Swiss mice and by inhalation to Sprague-Dawley rats. Ann. N.Y. Acad. Sci. 534, 352-366.

Olsen, G.W., S. Hearn, R.R. Cook and M.F. Currier. 1989. Mortality experience of a cohort of Louisiana chemical workers. J. Occup. Med. 31(1), 32-34.

Ott, M.G., L.K. Skory, B.B. Holder, J.M. Bronson and P.R. Williams. 1983a. Health evaluation of employees occupationally exposed to methylene chloride. General study design and environmental considerations. Scand. J. Work Environ. Health 9(suppl. 1), 1-7.

Ott, M.G., L.K. Skory, B.B. Holder, J.M. Bronson and P.R. Williams. 1983b. Health evaluation of employees occupationally exposed to methylene chloride. Mortality. Scand. J. Work Environ. Health 9(suppl. 1), 8-16.

Serota, D.G., A.K. Thakur, B.M. Ulland, J.C. Kirschman, N.M. Brown, R.H. Coots and K. Morgareidge. 1986a. A two-year drinking-water study of dichloromethane in rodents. II. Mice. Fd. Chem. Toxicol. 24(9), 959-963.

Serota, D.G., A.K. Thakur, B.M. Ulland, J.C. Kirschman, N.M. Brown, R.H. Coots and K. Morgareidge. 1986b. A two-year drinking-water study of dichloromethane in rodents. I. Rats. Fd. Chem. Toxicol. 24(9), 951-958.

Long, G., M.E. Meek, I. Caldwell, S. Bartlett and S. Savard. 1994. Dichloromethane: Evaluation of Risks to Health from Environmental Exposure in Canada. In: Environmental Carcinogenesis and Ecotoxicology Reviews, Part C of Journal of Environmental Science and Health. C12(2): 305-318.

Health Canada. 1996a. Health-Based Tolerable Daily Intakes/Concentrations and Tumourigenic Doses/Concentrations for Priority Substances. Ottawa: Ministry of Supply and Services Canada. H46-2/96-194E.

Health Canada. 1996b. Canadian Environmental Protection Act. Priority Substances List. Supporting Documentation: Health-Based Tolerable Daily Intakes/Concentrations and Tumourigenic Doses/Concentrations for Priority Substances (Unedited Version). This is the supporting document for Health Canada (1996a). Available at: http://www.tera.org/iter/HCPSL1supportdoc.pdf

Environment Canada, Health Canada. 1993. Priority substances list assessment report: dichloromethane. Ottawa. Ministry of Public Works and Government Services. Available at http://www.hc-sc.gc.ca/ewh-semt/pubs/contaminants/psl1-lsp1/index_e.html or at the Inquiry Centre at 1-800-668-6767 (in Canada) or 819-997-2800 (outside Canada).