dition of TLV®s makes the following recommendations:24
|Methyl Chloride||50 ppm (105 mg/m3), 8-hr TWA; 100 ppm (205 mg/m3), 15-minute TWA Short Term Exposure Limit (STEL)|
|Methyl Bromide||5 ppm (20 mg/m3), 8-hr TWA; 15 ppm (60 mg/m3), 15-minute STEL; Skin|
|Methyl Iodide||2 ppm (10 mg/m3), 8-hr TWA; 5 ppm (30 mg/m3), 15-minute STEL; A2; Skin|
The ACGIH has included methyl iodide in its list of suspected carcinogens, designated as Appendix A2 in the TLV® listing.24
The "Skin" notation for methyl bromide and methyl iodide in both the OSHA PEL's and the ACGIH TLV®s refers to the potential contribution to the overall exposure by the cutaneous route by either airborne or direct skin contact with the substance.
Results of Animal Studies
It has been reported that under similar testing conditions, the acute lethal concentrations capable of killing 50% of rats (LC50) exposed by inhalation for 30 minutes to methyl chloride, methyl bromide, or methyl iodide were 72,000 ppm, 2,800 ppm and 1,750 ppm, respectively.25 These data suggest that by this route of exposure methyl chloride is 26 times less toxic than methyl bromide and 41 times less toxic than methyl iodide.
Methyl chloride, methyl bromide, and methyl iodide were mutagenic for Salmonella typhimurium bacterial strains TA1535 and TA10.30,31 Because strain TA100 carries the same gene base-pair mutation as strain TA1535 and because both of these strains are sensitive to direct-acting, alkylating agents, a common mode of action for the three methylating agents is implied. An independent analysis of these data indicated that the relative mutagenic potencies of methyl chloride, methyl bromide, and methyl iodide were approximately in the ratios of 1:40:10.33 In addition, methyl bromide was found to be mutagenic in Escherichia coli bacteria,34 and methyl iodide was reported to be a direct-acting mutagen for mouse lymphoma L5178Y/TK+/-cells.35
Carcinogenic and Other Chronic Effects
In a 2-year methyl chloride inhalation study,26 male and female mice were exposed at concentrations of 0, 50, 225, or 1,000 ppm for six hours per day, five days per week. A statistically significant increase in both malignant and nonmalignant renal tumors occurred in only male mice exposed at the 1,000 ppm concentration. These tumors included cortical adenomas and adenocarcinomas, papillary cystadenomas and cystadenocarcinomas, plus tubular cystadenomas. In addition, 1,000 ppm of methyl chloride induced a functional limb muscle impairment and brain lesions in male and female mice, the latter being characterized by degeneration and atrophy of the granular layer of the cerebellum. Also, the male and female mice exposed at 1,000 ppm exhibited atrophy of the spleen.
Rats exposed to methyl chloride under the same experimental conditions, concentrations, and duration did not exhibit induction of cancer or the other lesions observed in the exposed mice.26
In a 90-day study,36 methyl bromide dissolved in arachis oil was administered by gastric gavage at levels of 0, 0.4, 2, 10, or 50 milligrams of methyl bromide per kilogram of body weight (mg/kg) five days per week to groups of 10 male and 10 female Wistar rats. Squamous cell carcinomas of the forestomach developed in a total of 13 of the 20 male and female rats treated with the 50 mg/kg dose. A dose-related incidence of hyperplasia was also noted in the rats at all levels except at 0 and 0.4 mg/kg.36
Methyl bromide is currently being studied in two laboratories.37 The National Institute for Public Health in the Netherlands is exposing rats by inhalation five days per week for their natural lifetimes at concentrations of 0, 3, 30, or 90 ppm. Final necropsies will be completed in 1985. The U.S. National Toxicology Program plans to begin a 2-year carcinogenicity study in late 1984 with mice exposed to methyl bromide.37
In a study designed to test the carcinogenic potential, of methyl iodide in mice susceptible to the induction of lung tumors,38 doses of 0, 0.36, 0.9 or 1.8 mg/kg were administered by intraperitoneal injection (IP) three days per week for eight weeks.