The carcinogenic risk associated with occupational exposure to methyl-chloride (74873), methyl-bromide (74839), and methyl-iodide (74884) is evaluated. Data is available on the mutagenicity and carcinogenicity of methyl-chloride, enabling the development of dose response models. For the other two compounds, little usable data is available, and the magnitude of human risk associated with these compounds is based on biological activities and likely mechanisms of action. By Ames assay, the relative mutagenic potency ratios of methyl-chloride, methyl-bromide, and methyl-iodide are 1 to 40 to 10. Methyl-chloride is a direct acting alkylating agent, a direct acting mutagen, and possibly an indirect acting mutagen. It appears to be a carcinogenic initiator, apparently with a linear dose response effect. The compound caused both benign and malignant kidney tumors and related preneoplastic lesions in male mice. Pharmacokinetic data indicate that the chemical is retained in the human body for long enough to be circulated to all potential cancer target organs. For a worker exposed to 1,000 parts per million (ppm) methyl-chloride for 40 hours a week for 54 years, the estimated lifetime cancer risk is 20 percent, according to a multistage model. With an exposure to 0.5pppm over this period, the maximum likelihood estimate of risk is 0.000000004 percent, according to this model. By the Weibull model, the corresponding risks for these exposure concentrations are 40 percent and 0.003 percent, respectively. Unlike methyl-chloride, the other two monohalomethanes appear to be broken down rapidly in the body; they are therefore less likely than methyl-chloride to reach distant target organs. Thus, they are more likely to act at sites of first contact, such as the lung. Their relative activity in initiating cancer is likely to be roughly in proportion to their relative alkylation activity and mutagenic potency. However, the authors conclude that there is insufficient information to make a formal risk assessment for methyl-bromide and methyl-iodide.
Division of Standards Development and Technology Transfer, NIOSH, U.S. Department of Health and Human Services