Methanol

CAS RN: 67-56-1

Toxicity Summary

IDENTIFICATION AND USE: Methanol is a clear colorless liquid, used in hydraulic fracturing mixtures. It is also used as dehydrator of natural gas; fuel for utility plants (methyl fuel); feedstock for manufacture of synthetic proteins by continuous fermentation; source of hydrogen for fuel cells, home-heating-oil extender. HUMAN STUDIES: Humans (and non-human primates) are uniquely sensitive to methanol poisoning. Nearly all of the available information on methanol toxicity in humans relates to the consequences of acute rather than chronic exposures. A vast majority of poisonings involving methanol have occurred from drinking adulterated beverages and from methanol-containing products. The minimum lethal dose of methanol in the absence of medical treatment is between 0.3 and 1 g/kg. Wide interindividual variability of the toxic dose is a prominent feature in acute methanol poisoning. Two important determinants of human susceptibility to methanol toxicity appear to be (1) concurrent ingestion of ethanol, which slows the entrance of methanol into the metabolic pathway, and (2) hepatic folate status, which governs the rate of formate detoxification. The symptoms and signs of methanol poisoning, which may not appear until after an asymptomatic period include visual disturbances, nausea, abdominal and muscle pain, dizziness, weakness and disturbances of consciousness ranging from coma to clonic seizures. Visual disturbances range from mild photophobia and misty or blurred vision to markedly reduced visual acuity and complete blindness. In extreme cases death results. The principal clinical feature is severe metabolic acidosis of the anion-gap type. ANIMAL STUDIES: The rate of metabolic detoxification, or removal of formate is vastly different between rodents and primates and is the basis for the dramatic differences in methanol toxicity observed between rodents and primates. The acute and short term toxicity of methanol varies greatly between different species, toxicity being highest in species with a relatively poor ability to metabolize formate. In such cases of poor metabolism of formate, fatal methanol poisoning occurs as a result of metabolic acidosis and neuronal toxicity, whereas, in animals that readily metabolize formate, consequences of CNS depression (coma, respiratory failure) are usually the cause of death. Overall methanol has a low acute toxicity to non-primate animals. In the rabbit, methanol is a moderate irritant to the eye. It was not skin sensitizing. The association between methanol exposure and lymphoma in some animal studies is weak, and is better interpreted as due to confounding factors or to a mechanism not relevant in humans. The inhalation of methanol by pregnant rodents throughout the period of embryogenesis induces a wide range of concentration-dependent teratogenic and embryolethal effects. Treatment-related malformations, primarily extra or rudimentary cervical ribs and urinary or cardiovascular defects, were found in fetuses of rats. Increased incidences of exencephaly and cleft palate were found in the offspring of mice. No increase in micronuclei was observed in the bone marrow of mice exposed to methanol. Methanol did not induce micronuclei in Chinese hamster lung V79 cells in vitro. Methanol was mutagenic in the mouse lymphoma assay, in a Basc test, or in Drosophila, sex-linked, recessive lethal mutation assay. Treatment of primary cultures of Syrian golden hamster embryo cells with methanol did not lead to cell transformation. Methanol was not mutagenic to Salmonella strains TA97, TA98, TA1535, TA 1537, and TA1538 in Ames tests with or without metabolic activation. Equivocal results were obtained with Salmonella strain TA102 in the presence of metabolic activation. Methanol was not mutagenic in a DNA-repair test using various strains of E. coli WP2 and in a forward mutation assay using Schizosaccharomyces pombe. ECOTOXICITY STUDIES: Methanol is of low toxicity to aquatic organisms, and effects due to environmental exposure to methanol are unlikely to be observed, except in the case of a spill.
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