Methanol appears as a colorless fairly volatile liquid with a faintly sweet pungent odor like that of ethyl alcohol. Completely mixes with water. The vapors are slightly heavier than air and may travel some distance to a source of ignition and flash back. Any accumulation of vapors in confined spaces, such as buildings or sewers, may explode if ignited. Used to make chemicals, to remove water from automotive and aviation fuels, as a solvent for paints and plastics, and as an ingredient in a wide variety of products.
颜色/状态：
Colorless liquid
气味：
Slight alcoholic odor when pure; repulsive, pungent odor when crude
蒸汽密度：
1.11 (NTP, 1992) (Relative to Air)
蒸汽压力：
VP: 92 mm Hg at 20 °C
亨利常数：
Henry's Law constant = 4.55X10-6 atm-cu m/mol at 25 °C
We recently showed that methanol emitted by wounded plants might function as a signaling molecule for plant-to-plant and plant-to-animal communications. In mammals, methanol is considered a poison because the enzyme alcohol dehydrogenase (ADH) converts methanol into ... formaldehyde /and other products/. However, the detection of methanol in the blood and exhaled air of healthy volunteers suggests that methanol may be a chemical with specific functions rather than a metabolic waste product. Using a genome-wide analysis of the mouse brain, we demonstrated that an increase in blood methanol concentration led to a change in the accumulation of mRNAs from genes primarily involved in detoxification processes and regulation of the alcohol/aldehyde dehydrogenases gene cluster. To test the role of ADH in the maintenance of low methanol concentration in the plasma, we used the specific ADH inhibitor 4-methylpyrazole (4-MP) and showed that intraperitoneal administration of 4-MP resulted in a significant increase in the plasma methanol, ethanol and formaldehyde concentrations. Removal of the intestine significantly decreased the rate of methanol addition to the plasma and suggested that the gut flora may be involved in the endogenous production of methanol. ADH in the liver was identified as the main enzyme for metabolizing methanol because an increase in the methanol and ethanol contents in the liver homogenate was observed after 4-MP administration into the portal vein. Liver mRNA quantification showed changes in the accumulation of mRNAs from genes involved in cell signaling and detoxification processes. We hypothesized that endogenous methanol acts as a regulator of homeostasis by controlling the mRNA synthesis.
Many studies have reported that methanol toxicity to primates is mainly associated with its metabolites, formaldehyde (FA) and formic acid. While methanol metabolism and toxicology have been best studied in peripheral organs, little study has focused on the brain and no study has reported experimental evidence that demonstrates transformation of methanol into FA in the primate brain. In this study, three rhesus macaques were given a single intracerebroventricular injection of methanol to investigate whether a metabolic process of methanol to FA occurs in nonhuman primate brain. Levels of FA in cerebrospinal fluid (CSF) were then assessed at different time points. A significant increase of FA levels was found at the 18th hour following a methanol injection. Moreover, the FA level returned to a normal physiological level at the 30th hour after the injection. These findings provide direct evidence that methanol is oxidized to FA in nonhuman primate brain and that a portion of the FA generated is released out of the brain cells. This study suggests that FA is produced from methanol metabolic processes in the nonhuman primate brain and that FA may play a significant role in methanol neurotoxicology.
Methanol is among the most common short-chain alcohols in fermenting fruits, the natural food and oviposition sites of the fruit fly Drosophila melanogaster. Our previous results showed that cytochrome P450 monooxygenases (CYPs) were associated with methanol detoxification in the larvae. Catalases, alcohol dehydrogenases (ADHs), esterases (ESTs) and glutathione S-transferases (GSTs) were specifically inhibited by 3-amino-1,2,4-triazole (3-AT), 4-methylpyrazole (4-MP), triphenyl phosphate (TPP) and diethylmeleate (DEM), respectively. CYPs were inhibited by piperonyl butoxide (PBO) and 1-aminobenzotriazole (1-ABT). In the present paper, the involvements of these enzymes in methanol metabolism were investigated in female and male adults by determining the combination indices of methanol and their corresponding inhibitors. When PBO, 1-ABT, 3-AT, 4-MP and TPP were individually mixed with methanol, they exhibited significant synergism to the mortality of the adults after 72 hr of dietary exposure. In contrast, the DEM and methanol mixture showed additive effects. Moreover, methanol exposure dramatically increased CYP activity and up-regulated mRNA expression levels of several Cyp genes. Bioassays using different strains revealed that the variation in ADH activity and RNAi-mediated knockdown of alpha-Est7 significantly changed LC50 values for methanol. These results suggest that CYPs, catalases, ADHs and ESTs are partially responsible for methanol elimination in adults. It seems that there are some differences in methanol metabolism between larvae and adults, but not between female and male adults.
Metabolism of methanol occurs in a three-step process initially involving oxidation to formaldehyde by hepatic alcohol dehydrogenase, which is a saturable rate-limiting process. In the second step, formaldehyde is oxidized by aldehyde dehydrogenase to formic acid or formate depending on the pH. In the third step, formic acid is detoxified by a folate-dependent pathway to carbon dioxide. Elimination of methanol from the blood appears to be slow in all species, especially when compared to ethanol. In humans, urinary methanol concentrations have been found to be proportional to the concentration of methanol in blood.
Methanol is metabolized to formaldehyde by alcohol dehydrogenase, then from that to formate by formaldehyde dehydrogenase, and then to carbon dioxide by limited H4 folate. (T10)
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.
The target of methanol in the eye is the retina, specifically the optic disk and optic nerve. Muller cells and rod and cone cells are altered functionally and structurally, because cytochrome oxidase activity in mitochondria is inhibited, resulting in a reduction in ATP. (T10)
来源:Toxin and Toxin Target Database (T3DB)
毒理性
致癌物分类
对人类不具有致癌性（未被国际癌症研究机构IARC列名）。
No indication of carcinogenicity to humans (not listed by IARC).
Acute methanol poisoning in humans is characterized by an asymptomatic period of 12h to 24h followed by formic acidemia, ocular toxicity, coma, and in extreme cases death. Visual disturbances develop between 18h to 48h after ingestion and range from mild photophobia and blurred vision to markedly reduced visual acuity and complete blindness. (T10)
来源:Toxin and Toxin Target Database (T3DB)
毒理性
暴露途径
这种物质可以通过吸入、皮肤接触和摄入被身体吸收。
The substance can be absorbed into the body by inhalation, through the skin and by ingestion.
来源:ILO-WHO International Chemical Safety Cards (ICSCs)
Methanol is absorbed following inhalation or ingestion, and inhalation is the major route of absorption in the occupational environment. There is no agreement on the potential risk of dermal exposure to methanol. Methanol is uniformly distributed according to the relative water content of the tissue.
The rate of absorption /of methanol from the gastrointestinal tract is approximately/... 8.4 mg/sq cm/hr. Time to peak serum concentration... after ingestion /is/... 30-60 minutes for methanol... .
... Under ... experimental conditions in man following ingestion and inhalation, dosages of 71-84 mg/kg orally resulted in blood levels of 4.7-7.6 mg/100 mL ... 2-3 hr afterward. urine/blood concentration ratio was ... constant at about 1.3. ... Inhalation of ... 500-1000 ppm ... for ... 3-4 hr gave urine concentration of about 1-3 mg/100 mL. ...
