 Among the mice given the highest dose (1.8 mg/kg), 9 of 20 animals died. The surviving 11 mice were killed 24 weeks after the first injection. Five of these 11 mice had developed lung tumors (statistically significant at p<0.05). Because of the early deaths of 45% of the mice, the experiment may not have demonstrated statistically convincing evidence of the carcinogenicity of methyl iodide.
In another study of methyl iodide,39 groups of 16 and 8 rats were given weekly subcutaneous injections (SC) of 10 mg/kg and 20 mg/kg of body weight, respectively, for approximately one year. Four of the rats in the 10 mg/kg group and two of the rats in the 20 mg/kg group died prematurely of pneumonia. Of the animals that survived, 9 of 12 in the 10 mg/kg group and 6 of 6 in the 20 mg/kg group developed sarcomas at the site of injection. In addition, two sarcomas at distant sites (a paravertebral osteogenic sarcoma and a differentiated sarcoma of the uterus) were identified in the 10 mg/kg group. The authors also reported that multiple metastases were seen in the lungs and lymph nodes. In a second part of this study, 14 rats were administered a single SC injection of 50 mg/kg methyl iodide and were observed for their lifetimes. Four of the rats developed local sarcomas between 446 and 654 days after the administration of the test material; two other rats developed differentiated sarcomas at distant sites (colon and vagina).
Teratogenicity and Reproductive Effects
Methyl chloride was reported to be teratogenic to the offspring of pregnant mice exposed by inhalation at concentrations of 0, 100, 250, 500, 750, or 1,500 ppm on days 6-18 of gestation. Exposure at the 1,500 ppm concentration was terminated early due to morbidity and death of the treated dams. A statistically significant number of fetal heart malformations was observed in the offspring exposed in utero at the 500 or 750 ppm concentrations. These malformations consisted of reduction in size or absence of the atrioventricular valves and attendant structures (chordae tendineae and papillary muscles). Exposure concentrations at 250 and 100 ppm were not teratogenic.40,41
Rats exposed to methyl chloride40 and rats and rabbits exposed to methyl bromide in another study42 showed no teratogenic effects. No teratology studies employing methyl iodide were found in the literature reviewed.
In addition to the previously described teratogenic effects, degeneration and atrophy of the seminiferous tubules were induced in male rats exposed by inhalation to methyl chloride at a concentration of 1,000 ppm.26 These effects were absent in rats exposed at 0, 50, and 225 ppm concentrations. Mice similarly exposed to methyl chloride exhibited no adverse reproductive effects.26
No studies on reproductive effects from exposure to methyl bromide or methyl iodide have been reported.
Human Health Effects
Most of the available information related to the toxic effects on humans exposed to methyl chloride, methyl bromide, methyl iodide is derived from accidental exposures to relatively high concentrations.
Symptoms of acute exposure to these compounds are relatively similar, consisting of headache, nausea, vomiting, drowsiness, dizziness, giddiness, diarrhea, confusion, ataxia, slurred speech, paralysis, convulsions, delirium, coma, and death.43-47 The lungs, liver, kidney, and brain appear to be the primary target organs in cases of severe poisoning.
No human studies to evaluate the possible mutagenic, carcinogenic, or teratogenic effects from exposure to these compounds are currently available.
The chemicals discussed in this bulletin, methyl chloride, methyl bromide, and methyl iodide, are alkylating agents that have been shown to induce cancer in rats and mice.
The studies which indicated the potential for these compounds to induce cancer in experimental animals are not without their shortcomings. The strains of animals used, the doses and routes selected for administration of the test compounds, and the fact that there was no coordinated study designed to test these compounds as a class impose limitat