Assessment of the cancer potential of methanol.
There are no published cancer studies of methanol-exposed cohorts. Genotoxicity studies do not suggest carcinogenic activity from methanol exposure. Oncogenicity studies of methanol were conducted by inhalation for approximately 20 hrs/day at up to 1000 ppm in F344 rats and B6C3F1 mice (NEDO), and by incorporation into drinking water at up to 20,000 ppm in Sprague-Dawley rats (Ramazzini Foundation, by Soffritti et al.). No increased neoplasms were found in the NEDO rat and mouse inhalation studies, even at air levels (up to 1000 ppm for >19 hours/day, 7 days/week) that caused 10-fold increased blood methanol levels. The maximum dose level was 600 mg/kg/day. The breakdown of methanol to formaldehyde in rats is saturated at doses above 600 mg/kg according to Horton et al. Thus, higher inhalation exposure concentrations are not expected to lead to tumors in rats or mice. In the Soffritti et al. study there was excessive early mortality, and lung pathology (inflammation, dysplasia, or neoplasm) was present in 87-94% of those dying anytime in the study. Soffritti et al. reported lympho-immunoblastic lymphoma. There are no historical control data to which this study can be compared because this diagnosis is not used by any other pathologist in animal studies. Lung infections probably played a role in formation of the lesions called lympho-immunoblastic lymphoma in the Ramazzini methanol study. The data from genotoxicity studies, the inhalation and drinking water oncogenicity studies of methanol in rats and mice, and mode of action considerations support a conclusion that methanol is not likely to be carcinogenic in humans.
Cruzan
George
G
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D000280:Administration, Inhalation; D000818:Animals; D015197:Carcinogenicity Tests; D002273:Carcinogens / Q000633:toxicity; D006801:Humans; D019570:Inhalation Exposure; D008168:Lung / Q000473:pathology; D000432:Methanol / Q000008:administration & dosage / Q000633:toxicity*; D051379:Mice; D008815:Mice, Inbred Strains; D009374:Neoplasms, Experimental / Q000473:pathology; D051381:Rats; D011916:Rats, Inbred F344; D017207:Rats, Sprague-Dawley; D018570:Risk Assessment; D018675:Toxicity Tests; D014874:Water Pollutants, Chemical / Q000633:toxicity; D014881:Water Supply / Q000032:analysis
D002273:Carcinogens; D014874:Water Pollutants, Chemical; D000432:Methanol