ons 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. 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 te