The following information was generated from the Hazardous Substances Data Bank (HSDB), a database of the National Library of Medicine's TOXNET system (http://toxnet.nlm.nih.gov) on February 24, 2011.

Query: Records containing the term METHANOL

1

NAME: METHANOL

HSN: 93

RN: 67-56-1

HUMAN HEALTH EFFECTS:

TOXICITY SUMMARY: Methanol occurs naturally in humans, animals and plants. It is a natural constituent in blood, urine, saliva and expired air. ... The two most important sources of background body burdens for methanol and formate are diet and metabolic processes. Methanol is available in the diet principally from fresh fruits and vegetables, fruit juices ... fermented beverages ... and diet foods (principally soft drinks). The artificial sweetner aspartame is widely used and, on hydrolysis, 10% (by weight) of the molecule is converted to free methanol, which is available for absorption. ... Exposures to methanol can occur in occupational settings through inhalation or dermal contact. ... Methanol is readily absorbed by inhalation, ingestion and dermal exposure, and it is rapidly distributed to tissues according to the distribution of body water. A small amount of methanol is excreted unchanged by the lungs and kidneys. ... Methanol is metabolized primarily in the liver by sequential oxidative steps to formaldehyde, formic acid and carbon dioxide. The initial step involves oxidation to formaldehyde by hepatic alcohol dehydrogenase ... In step 2, formaldehyde is oxidized by formaldehyde dehydrogenase to formic acid/or formate depending on the pH. In step 3, formic acid is detoxified to carbon dioxide by folate-dependent reactions. Elimination of methanol from the blood via the urine and exhaled air and by metabolism appears to be slow in all species, especially when compared to ethanol. ... It is the rate of metabolic detoxification, or removal of formate that 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, etc.) are usually the cause of death. Sensitive primate species (humans and monkeys) develop increased blood formate concentrations following methanol exposure, while resistant rodents, rabbits and dogs do not. Humans and non-human primates are uniquely sensitive to the toxic effects of methanol. 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 ... There is no evidence from animal studies to suggest that methanol is a carcinogen ... 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 ... There was increased embryo/fetal death ... and an increasing incidence of full litter resorptions. Reduced fetal weight

was observed ... Fetal malformations ... included neural and ocular defects, cleft palate, hydronephrosis and limb anomalies. Humans (and non-human primates) are uniquely sensitive to methanol poisoning and the toxic effects in these species are characterized by formic acidemia, metabolic acidosis, ocular toxicity, nervous system depression, blindness, coma and death. 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. Although ingestion dominates as the most frequent route of poisoning, inhalation of high concentrations of methanol vapor and percutaneous absorption of methanolic liquids are as effective as the oral route in producing acute toxic effects. The most noted health consequences of longer term exposure to lower levels of methanol is a broad range of ocular effects. ... The toxicity is manifest if formate generation

continues at a rate that exceeds its rate of metabolism. ... The minimum

lethal dose of methanol in the absence of medical treatment is between 0.3 and 1 g/kg. The minimum dose causing permanent visual defects is unknown. ... 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 

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2/24/2011 htt p ://toxnet.nlm.nih. g ov/c g i- b in/sis/download.txtdisturbances ... 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. The acidosis is largely attributed to the formic acid produced when methanol is metabolized. ... Visual disturbances of several types (blurring, constriction of the visible field, changes in color perception, and temporary or permanent blindness) have been reported in workers ... No other adverse effects of methanol have been reported in humans except minor skin and eye irritation. ... 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. [Environmental Health Criteria 196: Methanol pp. 1-9 (1997) by the International Programme on Chemical Safety (IPCS) under the joint sponsorship of the United Nations Environment Programme, the International Labour Organisation and the World Health Organization.] **PEER REVIEWED**

HUMAN TOXICITY EXCERPTS: /HUMAN EXPOSURE STUDIES/ ...Teacher aides who worked at or near spirit duplicators that used a 99% methanol duplicator fluid /were studied/. The exposures ranged from 1 hr/day for 1 day/wk to 8 hr/day for 5 days/wk and had occurred for 3 years. Since the introduction of the equipment, the aides began to experience headaches, dizziness and eye irritation, blurred vision and nausea/upset stomach while working near the machines. Fifteen-minute breathing zone samples near 21 operating machines contained between 475 and 4000 mg/cu m of methanol vapor. Fifteen of these samples exceeded the NIOSH recommended 15-min standard of 1050 mg/cu m (800 ppm). The aides were also exposed while collating and stapling papers impregnated with the fluid up to 3 hr earlier and these exposures ranged from 235-1140 mg/cu m . The results suggested that chronic effects may occur when methanol concentrations exceed the threshold limit value (TLV) of 260 mg/cu m (200 ppm). The effects reported in the study... were similar in nature but appeared less severe than those reported from acute poisoning by methanol [WHO; Environ Health Criteria 196: Methanol p.111 (1997). Available from, as of July 19, 2005: http://www.inchem.org/documents/ehc/ehc/ehc196.htm] **PEER REVIEWED**

/HUMAN EXPOSURE STUDIES/ The minimal lethal dose of methanol in humans has not been determined. It has been suggested that ingestion of about 1 g/kg can cause death if the patient is untreated and has not consumed ethanol. In 10 adults acutely intoxicated with methanol, a latency period before treatment exceeding 10 hr and a blood formate level above 0.5 g/L was reported to be predictive of severe methanol poisoning. [Bingham, E.; Cohrssen, B.; Powell, C.H.; Patty's Toxicology Volumes 1-9 5th ed. John Wiley & Sons. New York, N.Y. (2001)., p. V6 p.379] **PEER REVIEWED**

/HUMAN EXPOSURE STUDIES/ A study of the wooden heel industry in Massachusetts showed average methanol vapor concentrations ranging from 160 to 780 ppm, with no definite evidence of injury to the exposed workers. There was no mention of symptoms or complaints in spirit duplicating processes in which exposures ranged from 400 to 1000 ppm. In small, poorly ventilated rooms, headaches occurred among employees using methanol in duplicating machines. The air concentrations were calculated for two unventilated sizes of compartment and two types of Ditto fluid (one containing 5% and the other 45% methanol, though some fluids contained up to 100% methanol). Air concentrations from evaporation of 1 pint of fluid were as follows: 510 and 1000 ppm with 5% solutions for 1000- and 512- cu ft rooms, respectively; 4500 and 8870 ppm with 45% methanol solution, respectively. The human tolerance values for exposure for methanol were then determined. For single exposures, the estimated tolerance value was 1000 ppm for 1 hr, 500 ppm for 8 hr, 200 ppm for 24 hour, and 200 ppm for 40 hr, based on five 8 hr working days. [Bingham, E.; Cohrssen, B.; Powell, C.H.; Patty's Toxicology Volumes 1-9 5th ed. John Wiley & Sons. New York, N.Y. (2001)., p. V6 p.380] **PEER

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/HUMAN EXPOSURE STUDIES/ In 23 workers who, partly due to unfavorable working conditions (blackout precautions during wartime), had been exposed to methanol concentrations up to about 8300 ppm, no symptoms were seen apart from one case of "temporary blindness. " [Bingham, E.; Cohrssen, B.; Powell, C.H.; Patty's Toxicology Volumes 1-9 5th ed. John Wiley & Sons. New York, N.Y. (2001)., p. V6 p.380] **PEER REVIEWED**

/HUMAN EXPOSURE STUDIES/ From ophthalmoscopic and histological evidence, both the retina and the optic nerve have been postulated as the primary sites of the toxic lesion produced by formate in methanol poisoning. Permanent visual damage in methanol-poisoned humans is associated with exposures usually greater than 20 hr to blood formate concentrations in excess of 7 mM or 322 mg/dL. The initiating effect in the ocular toxicity of formic acid is believed to involve the inhibition of cytochrome oxidase, which is located in the mitochondria and is involved in oxidative phosphorylation. [Bingham, E.; Cohrssen, B.; Powell, C.H.; Patty's Toxicology Volumes 1-9 5th ed. John Wiley & Sons. New York, N.Y. (2001)., p. V6 p.380] **PEER REVIEWED**

/HUMAN EXPOSURE STUDIES/ The effects of methanol vapor (249 mg/cu m; SD + 7 mg/cu m) for 75 min on neurobehavioral measures were studied in 12 healthy young men. The exposure produced significant increases (approximately 3 fold) in blood and urine methanol levels but no changes in plasma formate level. Although most of the neurobehavioral end-points were unaffected by exposure to methanol, statistically significant effects and trends were found for a cluster of variables, including the latency of 

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2/24/2011 htt p ://toxnet.nlm.nih. g ov/c g i- b in/sis/download.txtthe p-200 component of event-related potentials, performance on the Sternberg memory task and subjective measures of fatigue and concentration. However, the effects were small and did not exceed the normal range. [WHO; Environ Health Criteria 196: Methanol p.113 (1997). Available from, as of July 19, 2005: http://www.inchem.org/documents/ehc/ehc/ehc196.htm] **PEER REVIEWED**

/HUMAN EXPOSURE STUDIES/ ...The charts of the patients/treated in the same intensive care unit for severe methanol poisoning/ admitted between 1987 and 2001 were reviewed. Inclusion criteria were: a history of deliberate methanol ingestion, with a blood methanol concentration > 20 mg/dL (6.2 mmol/L) or a high anion gap metabolic acidosis. Indications for hemodialysis were: blood methanol concentration > 50 mg/dL (15.8 mmol/L), metabolic acidosis (bicarbonate < 15 mmol/L, arterial pH < 7.30), visual toxicity. Antidotal therapy included ethanol administration in 22 cases, and fomepizole in 3 cases. Serial blood measurements were obtained for pH, bicarbonate, methanol and formate. Endogenous and hemodialysis elimination half-lives were calculated as t1/2 =0.693/Ke. Fick principle was applied for hemodialysis clearance calculation. The records of 25 methanol poisoned patients were analysed. Among them, 18 patients had sufficient data to allow accurate determinations of formate kinetics. Formate half-life elimination during hemodialysis was 1.80+/-0.78 hr, which was statistically different from the values observed before or in the absence of dialysis (6.04+/-3.26 hr, P=0.004). The mean hemodialysis formate clearance rate calculated in eight cases was 176+/-43 mL/min. A rebound in plasma formate concentration was observed in three patients after the discontinuation of hemodialysis. [Hantson P et al; Hum Exp Toxicol 24 (2): 55-9 (2005)] **PEER REVIEWED**

<a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15850279&query_hl=50" target=new>PubMed Abstract

/HUMAN EXPOSURE STUDIES/ ...This is a retrospective analysis of the medical records of 25 consecutive patients admitted to the intensive care unit after severe intentional methanol poisoning. Acute renal impairment was defined as a serum creatinine concentration higher than 177 micro mol/L and/or a urinary output on admission and for the first 24 hr below 0.5 mL/kg/hr. Clinical pathological signs of acute renal injury were found in 15 patients. In comparison with the 10 other patients taken as control group, the patients who developed renal injury had a lower blood pH value on admission, a higher serum osmolality, and a higher peak formate concentration. Two factors contributing to renal injury could be identified: hemolysis and myoglobinuria. The role of osmotic changes (osmotic nephrosis) or of a direct cytotoxic effect of formic acid remains speculative. Analysis of proteinuria suggests that proximal tubular cells may be preferentially affected. Results of histopathological evaluation of the kidney on a limited sample size (n=5) were inconclusive but suggestive of possible hydropic changes in the proximal tubule secondary to methanol toxicity. Acute renal injury may be associated with other signs of severity in methanol poisoning, but it is almost always reversible in survivors. Indicators of acute renal injury were identified. The pathophysiology of this acute renal injury is multifactorial and far more complex than shock-related tubular necrosis. [Verhelst D et al; Int J Toxicol 23 (4): 267-73 (2004)] **PEER REVIEWED** <a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15371171&query_hl=4" target=new>PubMed Abstract

/HUMAN EXPOSURE STUDIES/ ...Twenty-one-year retrospective chart review (1980-2000) from suspected methanol poisoning patients treated with ethanol in two large pediatric tertiary care centers. A total of 60 children (median age of 24 months) received ethanol for suspected methanol poisoning: 39 orally and 21 intravenously. Median initial methanol level was 4.16 mmol/L (13.3 mg/dL) (range 0 to 87.5 mmol/L or 0 to 280 mg/dL). Median duration of ethanol treatment was 16 hours (range 1.5 to 72 hours). None [0% (95% CI 0-5%)] of the 60 patients developed symptomatic hypoglycemia. Of the 50 patients that had a glucose level measured, none [(0% [95% CI 0-6%)] had a serum glucose concentration < 2.78 mmol/L ( < 50 mg/dL). Eight patients [16% (95% CI 8-30%)] had at least one serum glucose concentration between 2.78-3.61 mmol/L (50-65 mg/dL), but none of those had symptoms compatible with hypoglycemia. A total of 42 patients [84% (95% CI 70-92%)] had all their serum glucose concentrations > 3.61mmol/L ( > 65 mg/dL). There was no identifiable difference in the glucose intake between the serum glucose concentration groups. Six out of the 60 patients [10% (95% CI 4-21%)] were described as more drowsy

after ethanol but none was comatose or needed intubation. No child showed signs of hypothermia [0/40 (95% CI 0-8%)] (rectal temperature < 35 degrees C), hepatotoxicity (0/12) (AST or ALT > 100 U/L) or even thrombophlebitis (0/21). None of the 22 patients with toxic levels of methanol ( > or = 26.2 mmol/L- > or = 20 mg/dL) died or had ethanol-induced morbidity despite wide variation in ethanol levels. The rate of clinically important adverse effects related to ethanol used as an antidote to treat methanol poisoning in children was either absent or low in a tertiary care pediatric hospital setting. There was no morbidity or mortality associated with ethanol when it was used despite wide variation in ethanol levels. [Roy M et al; J Toxicol Clin Toxicol 41 (2): 155-61 (2003)] **PEER REVIEWED** <a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=12733853&query_hl=24" target=new>PubMed Abstract

/SIGNS AND SYMPTOMS/ SYMPTOMATOLOGY: A latency usually of 12-18 hours, during which time the only clinical signs are those of a generally mild 

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2/24/2011 htt p ://toxnet.nlm.nih. g ov/c g i- b in/sis/download.txtand transient state of inebriation as after ethanol. Headache, anorexia, weakness, fatigue, leg cramps, vertigo, restlessness. Nausea, occasionally vomiting and diarrhea. Violent abdominal pain, back pain, leg pain. Apathy or delirium progressing sometimes rapidly to coma. Rarely excitement, mania, and convulsions. Dimness of vision with dilated pupils, reacting poorly, if at all, to light, followed often by bilateral blindness (transient or permanent). Eyes are often sensitive to pressure, and eye movements are painful. Breathing is rapid and shallow, not usually deep and labored as seen in other types of metabolic acidosis. Mild tachycardia is common, but the blood pressure is usually well maintained. Death in coma is due to respiratory failure or rarely to circulatory collapse. Protracted convalescence with asthenia. Blindness is usually permanent. [Gosselin, R.E., R.P. Smith, H.C. Hodge. Clinical Toxicology of Commercial Products. 5th ed. Baltimore: Williams and Wilkins, 1984., p. III-277]

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/SIGNS AND SYMPTOMS/ Effects seen from either of the 2 most common routes of occupational exposure (inhalation and percutaneous absorption) include: headache, dizziness, nausea, vomiting, weakness, vertigo, chills, shooting pains in the lower extremities, unsteady gait, dermatitis, multiple neuritis characterized by paresthesia, numbness, prickling, and shooting pain in the back of the hands and forearms, as well as edema of the arms, nervousness, gastric pain, insomnia, acidosis, and formic acid in the urine. Eye effects, such as blurred vision, constricted visual fields, blindness, changes in color perception, double vision, and general visual disturbances have been reported. Eye examination have shown sluggish pupils, pallid optic discs, retinal edema, papilledema, hyperemia of the optic discs with blurred edges and dialated veins. [NIOSH; Criteria Document: Methyl Alcohol p.68-9 (1976) DHEW Pub. NIOSH 76-148] **PEER

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/SIGNS AND SYMPTOMS/ Acute methanol toxicity in humans is characterized in a well-defined pattern. Depending on the amount consumed, a narcotic effect varying from mild to severe results from central nervous system depression. This is followed by an asymptomatic interval lasting 10 to 48 hr, although 12 to 24 hr is most common. The latent period is then followed by headaches, nausea, dizziness, and vomiting, followed by severe abdominal pain and difficult, periodic breathing (Kussmaul breathing). The individual also experiences blurred vision, photophobia, and pains in the eyes. Depending on the amount of methanol consumed, the individual susceptibility and the time at which treatment began, these visual disturbances may either recede or develop within a few days into visual impairments or total blindness. The appearance of these symptoms coincides with increasing acidosis caused by accumulation of formic acid. In severe cases, this leads to coma and eventually death from respiratory failure. [Bingham, E.; Cohrssen, B.; Powell, C.H.; Patty's Toxicology Volumes 1-9 5th ed. John Wiley & Sons. New York, N.Y. (2001)., p. V6 p.380] **PEER

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/SIGNS AND SYMPTOMS/ The neurotoxic effects of methanol on the visual system can involve transient abnormalities such as peripapillary edema, optic disc hyperemia, diminished pupillary reactions to light, and central scotomata. Permanent ocular abnormalities include optic disc pallor, attenuation of arterioles, sheathing of arterioles, diminished pupillary reactions to light, diminished visual acuity, central scotomata, and other nerve fiber bundle defects. Pallor of the optic disc is an end-stage sign of irreversible effects of the visual system and may appear 1 to 2 months after an acute methanol dosage (or possibly following chronic occupational exposure to methanol vapor). [WHO; Environ Health Criteria 196: Methanol p.103 (1997). Available from, as of July 18, 2005: http://www.inchem.org/documents/ehc/ehc/ehc196.htm] **PEER REVIEWED**

/SIGNS AND SYMPTOMS/ ...A high frequency rate of DIC-syndrome is shown for the condition /of intoxication of alcohol surrogates/. A majority of thrombi accumulates at places with the highest concentrations of toxic substances as well as at those places, through which poisoning substances are brought out of the body, i.e. in the liver (since toxic substances are introduced perorally) and kidneys. Thrombi were detected in all internals, including the brain, in lethal intoxication. The immediate toxic effect from methanol and from higher spirits can matter in the genesis of changes, including acute swelling and chromatolysis with subsequent cell death. Exclusively cerebral or coagulopathic-cerebral types of thanatogenesis were registered in studied case of intoxication. [Bogomolova IN et al; Sud Med Ekspert 47 (5): 22-5 (2004)] **PEER

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/SIGNS AND SYMPTOMS/ There have been reports of diminished vision or blindness from skin application of methanol or preparations that contain methanol for the relief of pain, for the removal of varnish from skin, as well as following accidental exposure. The concentration of airborne methanol ranged from 365 to 3080 ppm; 15 of 21 measurements exceeded 800 ppm. [Bingham, E.; Cohrssen, B.; Powell, C.H.; Patty's Toxicology Volumes 1-9 5th ed. John Wiley & Sons. New York, N.Y. (2001)., p. V6 p.381]

**PEER REVIEWED**

/SIGNS AND SYMPTOMS/ Chronic poisoning from repeated exposure to methanol vapor were manifested by conjunctivitis, headache, giddiness, insomnia, gastric disturbances, and bilateral blindness. [American Conference of Governmental Industrial Hygienists. Documentation of Threshold Limit Values for Chemical Substances and Physical Agents and Biological Exposure Indices for 2001. Cincinnati, OH. 2001., p. 2] **PEER REVIEWED** 

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2/24/2011 htt p ://toxnet.nlm.nih. g ov/c g i- b in/sis/download.txt/SIGNS AND SYMPTOMS/ Symptoms... of methanol poisoning consist of headache, vertigo, vomiting, severe upper abdominal pain, back pain, dyspnea, motor restlessness, cold clammy extremities, blurring of vision, hyperemia of optic disc, ...diarrhea. ...Pulse is slow in severely ill patients, and bradycardia constitutes grave prognostic sign. [Hardman, J.G., L.E. Limbird, P.B., A.G. Gilman. Goodman and Gilman's The Pharmacological Basis of Therapeutics. 10th ed. New York, NY: McGraw-Hill, 2001., p. 1886] **PEER REVIEWED**

/SIGNS AND SYMPTOMS/ Visual disturbance, the most distinctive aspect of methanol poisoning in human beings, become evident soon after the onset of acidosis. Dialated, unreactive pupils and dim vision are characteristic. The ocular lesion, which involves chiefly the ganglion cells of the retina, is a destructive inflammation followed by atrophy. In the short term, the retina is congested and edematous, and the edges of the optic disc may be blurred. The final result is bilateral blindness, which is usually permanent. [Hardman, J.G., L.E. Limbird, P.B., A.G. Gilman. Goodman and Gilman's The Pharmacological Basis of Therapeutics. 10th ed. New York, NY: McGraw-Hill, 2001., p. 1886] **PEER REVIEWED**

/CASE REPORTS/ ...All methanol-poisoned patients admitted to /three intensive care units in university-affiliated teaching hospitals/ and treated with fomepizole from 1987-1999 (n=14) /were included in the retrospective clinical study/. The median plasma methanol concentration was 50 mg/dL (range 4-146), anion gap 22.1 mmol/L (11.8-42.2), arterial pH 7.34 (7.11-7.51), and bicarbonate 17.5 mmol/L (3.0-25.0). Patients received oral or intravenous fomepizole until blood methanol was undetectable. The median cumulative dose was 1250 mg (500-6000); the median number of twice daily doses was 2 (1-16). Four patients underwent hemodialysis for visual impairment present on admission. Four patients with plasma methanol concentrations of 50 mg/dL or higher and treated without hemodialysis recovered fully. Patients without pretreatment visual disturbances recovered, with no sequelae in any case. There were no deaths. Fomepizole was safe and well tolerated, even in the case of prolonged treatment. Analysis of methanol toxicokinetics in 5 patients demonstrated that fomepizole was effective in blocking methanol's toxic metabolism. Fomepizole appears safe and effective in the treatment of methanol-poisoned patients. [Megarbane B et al; Intensive Care Med 27 (8): 1370-8 (2001)] **PEER REVIEWED** <a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=11511951&query_hl=34" target=new>PubMed Abstract

/CASE REPORTS/ ...Two autopsy cases showing the classic neuropathologic injuries in acute methanol poisoning: putamen and white matter necrosis and hemorrhage /are presented/. In Case 1, putamen hemorrhages were striking; white matter pathology predominated in Case 2. The precise mechanism of methanol toxicity is unclear. Direct toxicity of metabolites, particularly formic acid, as well as ischemic injury and acidosis likely play a role. [Feany MB et al; Brain Pathol 11 (1): 121-2 (2001)] **PEER

REVIEWED** <a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=11145199&query_hl=36" target=new>PubMed Abstract

/CASE REPORTS/ ...A 27-yr-old man who was admitted 22 hours after poisoning and presented a peak blood methanol concentration of 12.9 g/L. Treatment included correction of metabolic acidosis, ethanol infusion, hemodialysis and peritoneal dialysis. The patient survived with moderate visual sequelae and esophageal stenosis. [Hantson P et al; Eur J Emerg Med 7 (3): 237-40 (2000)] **PEER REVIEWED** <a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=11142277&query_hl=38" target=new>PubMed Abstract

/CASE REPORTS/ ...Two cases of acute ocular damage following methanol ingestion are presented. One patient underwent extensive electrophysiological and psychophysical testing. Both patients reported transient visual disturbances. In each patient vision was 6/6 in both eyes at presentation but subsequently improved to 6/4. Color vision (Ishihara plates) and pupillary reactions were normal. The optic discs were hyperemic and swollen and retinal edema extended along the major vascular arcades. There was cystoid macular edema and 'pseudo cherry red spots' were observed. Automated field analysis revealed a generalized depression of retinal sensitivity, an enlargement of one blind spot and paracentral scotomas. The scotopic ERG was subnormal with diminished a- and b-waveforms and the cone response to flicker was reduced. The pattern VER P2 waveform was normal in latency but decreased in amplitude. ... [McKellar MJ et al: Aust N Z J Ophthalmol 25 (3): 225-30 (1997)] **PEER

REVIEWED** <a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=9296298&query_hl=44" target=new>PubMed Abstract

/CASE REPORTS/ A case is described of an experimental physicist who developed parkinsonism, apparently as delayed toxic effect of long exposure to vapors of methanol in the laboratory. Clinical and magnetic resonance imaging (MRI) supported the diagnosis, after exclusion of hereditary diseases and primary degenerative diseases. Screening for heavy metals in urine and plasma ceruloplasmin was negative. This case illustrates the neurotoxic delayed effect of long-term exposure to methanol with no episodes of acute intoxication. [Finkelstein Y, Vardi J; Neurotoxicology 23 (4-5): 521-25 (2002)] **PEER REVIEWED** <a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=12428724" 

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/CASE REPORTS/ ...A case of a 26-year-old woman who ingested 250-500 mL of methanol in the 38th week of pregnancy /was reported/. Five hours after methanol ingestion, the woman was slightly acidotic and had a serum methanol level of 2,300 mg/L and a formic acid concentration of 336 mg/L. Treatment consisted of ethanol and bicarbonate administration together with hemodialysis. Six days later, the woman gave birth to an infant with no signs of distress; Apgar scores were 9/10 and 10/10 at 1 and 5 minutes, respectively. At the time of birth, the blood formic acid level was 2.4 mg/L in the mother and was below the detection level in the infant. A 10 year follow-up of the child revealed no visual disturbances. [DHHS/NTP; NTP-CERHR Expert Panel Report on the Reproductive and Developmental Toxicity of Methanol p.52 (April 2002) NTP-CERHR-MeOH-02. Available from, as of July 20, 2005: http://cerhr.niehs.nih.gov/news/methanol/methanol_final.pdf] **PEER

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/CASE REPORTS/ Acute methanol intoxication in 24 men: 9 had no ocular effects; 7 had transient effects: Peripapillary edema, optic disc hyperemia, diminished pupillary light reaction, central scotoma. Eight had permanent optic disc pallor, arteriole attenuation and sheathing, diminished pupillary light reaction, diminished visual acuity, central scotoma, and other nerve fiber bundle effects. /There was/ complete blindness in 2, severe visual deficit in 4 /others/. [Dethlefs R, Naraqi S; Med J Aust 2 (10): 483-5 (1978)] **PEER REVIEWED** <a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=739940" target=new>PubMed Abstract

/CASE REPORTS/ Two cases which were described as multiple neuritis in men engaged in shellacking furniture with shellac dissolved in methyl alcohol /were reported/. Symptoms reported were paresthesia, numbing, prickling, and shooting pain in the back of the hands and forearms, in addition to edema of the arms. Both men sought medical aid promptly, and the resultant cessation of exposure probably prevented the development of serious sequelae of methyl alcohol intoxication. It was considered that these 2 cases were due to the inhalation of the vapor of the wood alcohol employed. [Jelliffe SE; Med News 86: 387-90 (1905) as cited in NIOSH; Criteria Document: Methyl Alcohol p.27-8 (1976) DHEW Pub. NIOSH 76-148]

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/CASE REPORTS/ The case of a businessman who had been in the habit of drinking quite regularly, in small quantities, for a period of at least 3 months an illicit whiskey which apparently contained 35% Columbian spirits (methyl alcohol). When observed, the subject was suffering from severe gastric irritability, marked hyperesthesia in both arms and hands, incomplete paralysis of the extensors, and waist drop. He also had a mild degree of ptosis of the eyelids and a restricted partial amblyopia. He recovered after 4 months of treatment but still had some residual blurring of vision. [Jelliffe SE; Med News 86: 387-90 (1905) as cited in NIOSH; Criteria Document: Methyl Alcohol p.28 (1976) DHEW Pub. NIOSH 76-148]

**PEER REVIEWED**

/CASE REPORTS/ A case of methyl alcohol poisoning in a worker who was involved in varnishing the inside of beer vats /is described/. Work commenced on December 3, 1911, and continued on the following day with no medical complaints. On December 5, the worker experienced headache, vertigo, unsteady gait, nausea, vomiting, and acted as if intoxicated; consequently he did not work on this day. On December 7, the worker began having visual disturbances. At this time, he consulted a physician who diagnosed methyl alcohol poisoning. On December 12, an ophthalmologist made the following observations: the pupils were practically nonreactive to light, there was retinal edema, and initial vision (eccentric) was right 1/200 and left 2/200. In three weeks, his vision had improved to 20/30 in each eye. Six to 7 months later, with no additional methyl alcohol exposure, visual acuity remained stable, while pupillary response to light remained sluggish. In addition, researchers described a progressive contraction of the visual fields during the entire period of observation. ...The progressive constriction of visual fields corresponded to degenerated bundles of fibers and groups of ganglion cells becoming confluent as the degenerative process spread. It was concluded that this case was produced solely by inhalation of methyl alcohol vapor. The airborne concentration of methyl alcohol to which the worker was exposed was not determined. [Tyson HH; Arch Ophthalmol 16: 459-71 (1912) as cited in NIOSH; Criteria Document: Methyl Alcohol p.29 (1976) DHEW Pub. NIOSH 76-148] **PEER REVIEWED**

/CASE REPORTS/ ...Five patients that presented to the /emergency department/ (ED) following deliberate solvent inhalation were evaluated for elevated methanol levels. All were abusing the solvent for 6-12 hours prior to arrival and were chronic abusers of this product. The initial mean /methanol/ (MeOH) level was 19.3 mg/dL (range 10-26). The initial serum bicarbonate ranged from 13 to 20 mmol/L and the initial anion gap ranged from 13 to 31. The mean serum formate level was 31.7 ug/mL (range 3.6-64) with a reference range of 0-12. All had an undetectable ethanol level. No patient had visual complaints and all had normal visual acuity. No patients were treated with an alcohol dehydrogenase inhibitor or dialysis, though all received intravenous folate. All had improved acidosis within 4 hours of arrival to the ED. [Bebarta V et al; J Toxicol Clin Toxicol 41 (5): 674-675 (2003)] **PEER REVIEWED** 

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2/24/2011 htt p ://toxnet.nlm.nih. g ov/c g i- b in/sis/download.txt/CASE REPORTS/ Reports of cases of poisoning due to methanol inhalation are relatively rare, although in one report there had been about 100 known cases of failing sight or death due to inhalation of "wood alcohol. " Usually exposure was in more confined spaces with poor ventilation. There was one case reported of a woman who died after inhaling 4000 to 13,000 ppm methanol over 12 hr. [Bingham, E.; Cohrssen, B.; Powell, C.H.; Patty's Toxicology Volumes 1-9 5th ed. John Wiley & Sons. New York, N.Y. (2001)., p. V6 p.380] **PEER REVIEWED**

/CASE REPORTS/ /A/ case involved a painter who spent three days painting the engine room of a submarine with a methanol containing varnish. No details were given of the varnish composition or the methanol concentration in the air. On the first day, the painter experienced dizziness; on the second day, he showed exuberance; and on the third day, increased irritability. He also complained of abdominal pain, insomnia, double vision, and ptosis (drooping eyelids). The patient's sight became severely restricted in the left eye, pupils dilated, the optic disks pallid, and the retinal vein engorged. His gait became uncoordinated, and he suffered acidosis. Under treatment, the patient's condition improved gradually over three weeks, and his sight eventually returned to normal. [Bingham, E.; Cohrssen, B.; Powell, C.H.; Patty's Toxicology Volumes 1-9 5th ed. John Wiley & Sons. New York, N.Y. (2001)., p. V6 p.380] **PEER

REVIEWED**

/CASE REPORTS/ An outbreak of acute methanol intoxication involving 28 young men in Papua New Guinea in 1977, each of whom consumed an equivalent of 60-600 mL pure methanol, resulted in all becoming hospitalized within 8-36 hr due to acute metabolic acidosis, severe visual impairment and acute pancreatitis. Four died within 72 hr after hospitalization. Of 24 who recovered, 16 showed no residual complications, 6 had bilateral visual impairment and 2 had difficulty in speech as well as visual impairment. [WHO; Environ Health Criteria 196: Methanol p.101 (1997). Available from, as of July 18, 2005: http://www.inchem.org/documents/ehc/ehc/ehc196.htm]

**PEER REVIEWED**

/CASE REPORTS/ ...In Atlanta, Georgia, USA, in 1951, when within a 5-day period, 323 people consumed bootlegged whiskey contaminated with 35-40% methanol and 41 of them died. ...The poisoning of 18 individuals /was reported/, of whom 8 died, when a diluted paint thinner containing approximately 37% (by volume) methanol was used as an alcoholic beverage in Lexington, Kentucky, USA. An epidemic in the State Prison of Southern Michigan in 1979 in which methanol diluent used in photocopying machines was used as "home-made" spirits (containing approximately 3% methanol)

resulted in 46 definite cases of methanol intoxication and 3 deaths. Methanol poisoning among 23 servicemen in an Army hospital in Korea who had ingested bootleg sake contaminated with methanol was reported. ...Acute methanol poisoning in 49 naval personnel who consumed drinks made from duplicating fluid containing a high concentration of methanol /was also reported/. [WHO; Environ Health Criteria 196: Methanol p.101 (1997). Available from, as of July 18, 2005: http://www.inchem.org/documents/ehc/ehc/ehc196.htm] **PEER REVIEWED**

/CASE REPORTS/ A case was reported of a 46-yr-old man who, after consuming a beverage containing methanol, exhibited one of the highest reported serum methanol levels (4930 mg/L), well above those at which ethanol treatment and hemodialysis are recommended (200 mg/L and 500 mg/L, respectively). The lowest serum pH was 7.0 with a hydrogen carbonate level of 8.8 and an anion gap of 42.8. Additionally, his visual acuity decreased to a complete loss of vision. The patient was aggressively treated with hemodialysis and ethanol infusion, regained his vision with a visual acuity of 20/30 bilaterally and suffered no neurological sequelae. [WHO; Environ Health Criteria 196: Methanol p.104 (1997). Available from, as of July 18, 2005: http://www.inchem.org/documents/ehc/ehc/ehc196.htm] **PEER

REVIEWED**

/CASE REPORTS/ Extensive white and grey matter brain damage was seen in an alcoholic 37-year-old man who consumed 1900 mL of windshield washer fluid containing methanol. Both CT scan and MR imaging revealed diffuse white matter edema and damage throughout frontal and parietal lobes. Bilateral changes in the basal ganglia and necrosis and hemorrhage of putamen were also noted. Autopsies from victims of lethal methanol poisonings revealed gross pathology in the visceral organs, the brain, lung, liver, kidney and the CNS, all of which involved a variety of edematous, hemorrhagic and degenerative changes. [WHO; Environ Health Criteria 196: Methanol p.105 (1997). Available from, as of July 18, 2005: http://www.inchem.org/documents/ehc/ehc/ehc196.htm] **PEER REVIEWED**

/CASE REPORTS/ A 39-yr-old woman intentionally ingested Amberes shoe dye containing both methanol and aniline. She subsequently developed life-threatening methanol poisoning, methemoglobinemia, hemolytic anemia, and sulfhemoglobinemia. Treatment involved methylene blue infusion, emergent hemodialysis, fomepizole therapy, and blood products. [Katz KD et al; J Emerg Med 27 (4): 367-9 (2004)] **PEER REVIEWED** <a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15498617&query_hl=56" target=new>PubMed Abstract

/CASE REPORTS/ ...A 28-yr-old pregnant woman EGA 30 weeks with HIV infection and asthma presented to the emergency department in respiratory distress. She was acidotic (pH 7.17) with an anion gap of 26, and fetal bradycardia was noted. Her son was delivered by emergency C-section (birthweight 950 g, Apgars 1 and 3) and required aggressive resuscitation. 

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2/24/2011 htt p ://toxnet.nlm.nih. g ov/c g i- b in/sis/download.txtDuring his hospital course, acidosis (initial pH 6.9) persisted despite fluid, blood, and bicarbonate administration. His mother also had persistent metabolic acidosis despite fluids, bicarbonate, and dopamine. Results of other laboratory tests on the mother included undetectable ethanol and salicylates and an osmolar gap of 41. An ethanol drip was

initiated for the mother 36 hr after admission when a methanol level of 54 mg/dL was reported. When consulted on hospital day 3, our regional poison center recommended hemodialysis for the mother and administering fomepizole and testing the methanol level of the newborn (61.6 mg/dL). Because the infant developed a grade 4 intraventricular bleed, no further therapy was offered, and he died on day 4. His mother died on day 10. [Belson M, Morgan BW; J Toxicol Clin Toxicol 42 (5): 673-7 (2004)] **PEER

REVIEWED** <a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15462163&query_hl=1" target=new>PubMed Abstract

/CASE REPORTS/ Treatment thresholds for methanol poisoning are based on case reports and published opinion. Most guidelines recommend treatment for a methanol level > or = 20 mg/dL in a nonacidotic patient. No supportive data have been offered nor has the time of the exposure been addressed. For instance, no distinction has been drawn between a methanol level drawn 1 hr vs. 24 hr from ingestion. ...All published cases of methanol poisoning /were analyzed/ to determine the applicability of the 20 mg/dL threshold in a nonacidotic patient, specifically those arriving early for care (within 6 hr) with a peak or near-peak blood methanol concentration. ...Dating to 1879, 372 articles in 18 languages were abstracted using a standard format; 329 articles (2433 patients) involved methanol poisoning, and 70 articles (173 patients) met inclusion criteria. Only 22 of these patients presented for care within 6 hr of ingestion with an early methanol level. All but 1 patient was treated with an inhibitor of alcohol dehydrogenase (ADH). A clear acidosis developed only with a methanol level > or = 126 mg/dL. The patient that did not receive an ADH inhibitor was an infant with an elevated early methanol level (46 mg/dL) that was given folate alone and never became acidotic. Intra and inter-rater reliability were 0.95. Nearly all reports of methanol poisoning involve acidotic patients far removed from ingestion. The small amount of data regarding patients arriving early show that 126 mg/dL is the lowest early blood methanol level ever clearly associated with acidosis. Contrary to conventional teaching, there are case reports of acidosis after only a few hours of ingestion. The data are insufficient to apply 20 mg/dL as a treatment threshold in a nonacidotic patient arriving early for care. [Kostic MA, Dart RC; J Toxicol Clin Toxicol 41 (6): 793-800 (2003)] **PEER REVIEWED** <a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=14677789&query_hl=20" target=new>PubMed Abstract

/CASE REPORTS/ ...An adult male presented with central blindness after ingesting methanol. Initial visual acuity was < 20/800 (finger counting at 1-2 feet) with retinal edema on fundoscopy, arterial pH 7.19, methanol 97 mg/dL (30 mmol/L), formate 14.3 mmol/L, and ethanol undetectable. The patient was treated with ethanol, then fomepizole intravenously (15, 10, then 5 mg/kg), and hemodialysis. Methanol metabolism was effectively blocked by fomepizole even after ethanol had been eliminated, and the patient recovered 20/20 vision by day 14 with normal fundoscopy. This case report confirms highly efficient inhibition of alcohol dehydrogenase by fomepizole, as well as demonstrate the safety of fomepizole in a patient already exhibiting end-organ retinal toxicity. The potential for fomepizole to inhibit retinol dehydrogenase, an isoenzyme of alcohol dehydrogenase essential to vision, did not appear to be clinically significant in this symptomatic methanol-poisoned patient. [Sivilotti ML et al; J Toxicol Clin Toxicol 39 (6): 627-31 (2001)] **PEER REVIEWED** <a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=11762672&query_hl=32" target=new>PubMed Abstract

/BIOMONITORING/ Volunteers in the dermal exposure portion of the experiment ... consisted of the four subjects who participated in the inhalation study and four additional male subjects (age 26-33 years). Mean pre-exposure blood and breath methanol levels were measured at 1.2 mg/L and 0.2 ppm, respectively. One hand from each volunteer was placed in a beaker containing neat methanol (99.8% purity) for time periods of 0, 2, 4, 8, and 16 minutes. Blood and breath methanol samples were taken immediately after exposure and at 12 additional time points for 8 hours following exposure. ... Blood and breath methanol concentrations peaked at about 45 and 15 minutes following exposure and were measured at 11.3 mg/L and 9.3 ppm, respectively. Authors noted that exposure to one hand ( < 3% of body surface area) for 16 minutes resulted in a blood methanol concentration that is about equal to that achieved by breathing 400 ppm methanol vapors for 8 hours. It was speculated by study authors that the rapid rise in breath, compared to blood methanol levels, occurs because methanol is first transported to the central circulation and lungs prior to becoming equally distributed throughout all body water. The study authors estimated that following a dermal exposure, 2 hours would need to pass before methanol blood concentrations could be estimated from breath levels. [DHHS/NTP; NTP-CERHR Expert Panel Report on the Reproductive and Developmental Toxicity of Methanol p.14 (April 2002) NTP-CERHR-MeOH-02. Available from, as of July 20, 2005: http://cerhr.niehs.nih.gov/news/methanol/methanol_final.pdf] **PEER

REVIEWED**

/BIOMONITORING/ ...A study /was conducted/ to determine if methanol in breath is a useful indicator of blood levels following oral or dermal 

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2/24/2011 htt p ://toxnet.nlm.nih. g ov/c g i- b in/sis/download.txtexposure. ... In the inhalation portion of the experiment, mean pre-exposure blood and breath methanol concentrations were measured at 2.65 mg/L and 1.3 ppm, respectively, in 4 subjects (3 males and 1 female, age 31-55 years). Each subject was exposed to 0, 100, 200, 400, and 800 ppm methanol vapors [purity not specified] for 8 hours. ... Following 6 and 8 hours of exposure, 4 blood and breath samples were taken at 5-minute intervals. ... Blood and breath levels of methanol were significantly increased at 6 and 8 hours. Peak blood levels were 11.1 and 13.4 mg/L at each respective time period. Breath concentrations were highest immediately after the 6- and 8-hour exposure (71.7 and 76.9 ppm, respectively), but rapidly declined within 15 minutes of breathing clean air (3.5 and 3.3 ppm). The authors suggested that the initial high concentration of breath methanol reflected absorption and desorption of methanol from airways. Therefore, the authors concluded that methanol breath levels would be useful for estimating blood concentrations only after 10-15 minutes of breathing clean air because that is the time needed for desorption of methanol from airways. [DHHS/NTP; NTP-CERHR Expert Panel Report on the Reproductive and Developmental Toxicity of Methanol p.14 (April 2002) NTP-CERHR-MeOH-02. Available from, as of July 20, 2005: http://cerhr.niehs.nih.gov/news/methanol/methanol_final.pdf] **PEER

REVIEWED**

/OTHER TOXICITY INFORMATION/ Methanol toxicity in humans ... is characterized by a latent period of many hours followed by a metabolic acidosis and ocular toxicity. This is not observed in most lower animals. The metabolic acidosis and blindness is apparently due to formic acid

accumulation in humans ... a feature not seen in lower animals. The accumulation of formate is due to a deficiency in formate metabolism, which is, in turn, related, in part, to low hepatic tetrahydrofolate (H4 folate). An excellent correlation between hepatic H4 folate and formate oxidation rates has been shown within and across species. Thus, humans ... possess low hepatic H4 folate levels, low rates of formate oxidation and accumulation of formate after methanol. Formate, itself, produces blindness ... humans also have low hepatic 10-formyl H4 folate dehydrogenase levels, the enzyme which is the ultimate catalyst for conversion of formate to carbon dioxide. [Tephly TR; Life Scl 48 (11): 1031-41 (1991)] **PEER REVIEWED**

/OTHER TOXICITY INFORMATION/ ...Experience with 16 organ donors who died as a result of acute methanol intoxication in 10 Spanish hospitals over the last 14 yr /is presented/. Between October 1985 and July 1999, 16 organ donors with brain death caused by acute methanol intoxication, 13 females and three males with a mean age of 38.4 +/- 7.6 yr (interval: 26-55 yr), allowed 37 elective transplants to be performed: 29 kidneys, four hearts and four livers for 37 recipients, and one urgent liver transplantation to a recipient with fulminant hepatitis. The immediate postoperative period was favorable for the 38 graft recipients. None of the graft recipients presented gap anion metabolic acidosis in the immediate postoperative period, nor symptomatology or lesions of the CNS characteristic of methanol intoxication. Two patients died during the first month post-transplantation, a liver recipient and a heart recipient, at 16 and 24 days, respectively, because of acute rejection of the graft. At 1 month after transplantation 35 of the 36 recipients had been discharged from hospital with normal-functioning grafts. The last of the recipients, a kidney recipient, was discharged at 6 wk with normal-functioning graft. Actuarial survival of the graft and patient of kidney recipients at 1, 3 and 5 yr was 92.6, 77.8, and 75%, and 100, 88.9 and 83.3%, respectively; with average serum creatinines of 139.9 +/- 42.9, 150.4 +/- 42.8, and 164.4 +/- 82.5 micromol/L, respectively. At 1 yr after transplantation the three heart recipients and two of the three liver recipients had normal-functioning graft. Methanol intoxication is not transferred from the donor to the recipient. The survival of the graft and kidney, heart and liver recipients using organs from donors who die because of methanol does not differ in the short- and long-term from the transplants performed with organs from donors who die from other causes. [Lopez-Navidad A et al; Clin Transplant 16 (3): 151-62 (2002)] **PEER

REVIEWED** <a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=12010136&query_hl=28" target=new>PubMed Abstract

/OTHER TOXICITY INFORMATION/ ...Published information about methanol-intoxicated patients is reviewed and combined with findings in studies in volunteers given small doses of methanol, as well as occupational exposure limits (OELs), to indicate a tolerable ("safe") daily dose of methanol in an adult as 2 g and a toxic dose as 8 g. The simultaneous ingestion of ethanol has no appreciable effect on the proposed "safe" and "toxic" doses when considering exposure over several hours. Thus, assuming that an adult consumes 4 x 25-mL standard measures of a drink containing 40% alcohol by volume over a period of 2 hr, the maximum tolerable concentration (MTC) of methanol in such a drink would be 2% (v/v) by volume. However, this value only allows a safety factor of 4

to cover variation in the volume consumed and for the effects of malnutrition (i.e., folate deficiency), ill health and other personal factors (i.e., ethnicity). In contrast, the current EU general limit for naturally occurring methanol of 10 g methanol/l ethanol [which equates to 0.4% (v/v) methanol at 40% alcohol] provides a greater margin of safety. [Paine A, Davan AD; Hum Exp Toxicol 20 (11): 563-8 (2001)] **PEER

REVIEWED** <a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=11926610&query_hl=30" target=new>PubMed Abstract 

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2/24/2011 htt p ://toxnet.nlm.nih. g ov/c g i- b in/sis/download.txtSKIN, EYE AND RESPIRATORY IRRITATIONS: /Methanol/ is an eye and skin irritant. [Lewis, R.J. Sax's Dangerous Properties of Industrial Materials. 9th ed. Volumes 1-3. New York, NY: Van Nostrand Reinhold, 1996., p. 2174] **PEER REVIEWED**

MEDICAL SURVEILLANCE: The following medical procedures should be made available to each employee who is exposed to methyl alcohol at potentially hazardous levels: 1. A complete history and physical examination should be given to detect existing conditions that might place the employee at increased risk, and to establish a baseline for future health monitoring. Examination of the skin, liver, kidneys, and eyes should be stressed. Skin disease: Methyl alcohol is a defatting agent and can cause dermatitis on prolonged exposure. Persons with ... existing skin disorders may be susceptible to the effects of this agent. Liver function tests: Methyl alcohol may cause liver damage. A profile of liver function should be obtained by utilizing a medically acceptable array of biochemical tests. Kidney disease: Although methyl alcohol has not been proven to be kidney toxin in humans, the importance of this organ in the elimination of toxic substances justifies special consideration in those with impaired renal function. Eye disease: Because methyl alcohol may cause optic atrophy and blindness, those with existing eye diseases may be at increased risk from exposure. The aforementioned medical examinations should be repeated on an annual basis. In addition, anyone developing the above-listed conditions or who has been splashed in the eyes with, has ingested, or otherwise has been exposed to methyl alcohol should be placed under medical surveillance. [Mackison, F. W., R. S. Stricoff, and L. J. Partridge, Jr. (eds.). NIOSH/OSHA - Occupational Health Guidelines for Chemical Hazards. DHHS(NIOSH) Publication No. 81-123 (3 VOLS). Washington, DC: U.S. Government Printing Office, Jan. 1981., p. 1] **PEER REVIEWED**

Special tests which may be used include: Determination of methyl alcohol in blood and methyl alcohol and formic acid in urine; estimation of alkali reserve which may be impaired because of acidosis following accidental ingestion. [Sittig, M. Handbook of Toxic and Hazardous Chemicals and Carcinogens, 1985. 2nd ed. Park Ridge, NJ: Noyes Data Corporation, 1985., p. 583] **PEER REVIEWED**

A study was performed among 20 workers employed in a printing office at 3 different work places (methanol concentration of 85, 101 and 134 ppm) to

determine whether the concentration of formic acid in blood or urine and the methanol content of alveolar air permit the estimation of methanol exposure. Blood, urine and end expiratory air were collected at the beginning and the end of the shift. For comparison formic acid concentrations were determined in the morning and in the afternoon in blood and urine of 36 and 15 control persons, respectively. The concentration of formic acid in blood increased significantly from 3.2:2.4 mg/L before to 7.9:3.2 mg/L after the shift in the exposed workers (mean increase 4.7:3.8 mg/L). The corresponding concentrations in urine were 13.1:5.3 mg/l. This difference is also significant. In the control groups there was a small but significant decrease of formic acid concentration in blood from 5.6:4.5 mg/L in the morning to 4.9:4.2 mg/L in the afternoon. In urine, the formic acid concentrations in the morning (11.9:6.4 mg/L) and in the afternoon (11.7:5.6 mg/L) were not significantly different. The increase of formic acid concentration in blood during the shift is the most useful parameter for monitoring methanol-exposed persons. [Baumann K, Angerer J; Int Arch Occup Environ Health 42 (3-4): 241-9 (1979)] **PEER

REVIEWED** <a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=422265" target=new>PubMed Abstract

A sampling strategy was developed to detect personal exposure to methanol and formic acid vapors. Formic acid is the metabolic end product of methanol, and part of inhaled formic acid is excreted directly in urine, so that urinary formic acid would reveal exposure to both agents. A linear relationship to inhaled vapors, however, could be shown only if urinary sampling were delayed until 16 hr (next morning) after exposure. Exposure to methanol vapor at the current Finnish hygienic limit level (200 ppm) produced 80 mg formic acid/g creatinine; exposure to formic acid at the hygienic limit (5 ppm) caused 90 mg/g creatinine. The similarity of these figures may indicate a common toxicological foundation of these empirically set values. [Liesivuori J, Savolainen H; Am Ind Hyg Assoc J 48 (1): 32-34 (1987)] **PEER REVIEWED** <a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=3565260" target=new>PubMed Abstract

Headspace gas chromatography was used to determine the concentration of ethanol and methanol in blood samples from 519 individuals suspected of drinking and driving in Sweden where the legal alcohol limit is 0.50 mg/g in whole blood (11 mmol/L). The concentration of ethanol in blood ranged from 0.01 to 3.52 mg/g with a mean of 1.83 + or - 0.82 mg/g (+ or - standard deviation). The frequency distribution was symmetrical about the mean but deviated from normality. A plot of the same data on normal probability paper indicated that it might be composed of two subpopulations (bimodal). The concentration of methanol in the same blood specimens ranged from 1 to 23 mg/L with a mean of 7.3 + or - 3.6 mg/L (+ or - standard deviation) and this distribution was markedly skew (+). The concentration of ethanol (x) and methanol (y) were positively correlated (r= 0.47, P < 0.001) and implies that 22% (r2) of the variance in blood-methanol can be attributed to its linear regression on blood-ethanol. The regression equation was y= 3.6 + 2.1 x and the standard 

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2/24/2011 htt p ://toxnet.nlm.nih. g ov/c g i- b in/sis/download.txterror estimate was 0.32 mg/L. This large scatter precludes making reliable

estimates of blood-methanol concentration from measurements of blood-ethanol concentration and the regression equation. But higher blood-methanol concentrations are definitely associated with higher blood-ethanol in this sample of Swedish drinking drivers. Frequent exposure to methanol and its toxic products of metabolism, formaldehyde and formic acid, might constitute an additional health risk associated with heavy drinking in predisposed individuals. The determination of methanol in blood of drinking drivers in addition to ethanol could indicate long-standing ethanol intoxication and therfore potential problem drinkers or alcoholics. [Jones AW, Lowinger H; Forensic Sci Int 37 (4): 277-85 (1988)] **PEER REVIEWED** <a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=3410397" target=new>PubMed Abstract

POPULATIONS AT SPECIAL RISK: Persons with existing skin, kidney, liver, or eye disorders may be at an increased risk when exposed to methanol. [Mackison, F. W., R. S. Stricoff, and L. J. Partridge, Jr. (eds.). NIOSH/OSHA - Occupational Health Guidelines for Chemical Hazards. DHHS(NIOSH) Publication No. 81-123 (3 VOLS). Washington, DC: U.S. Government Printing Office, Jan. 1981., p. 1]

**PEER REVIEWED**

Folate-deficient individuals might be at greater risk from inhalation of low concentrations of methanol, compared to normal individuals. Human populations that are potentially at high risk of folate deficiency include pregnant women, the elderly, individuals with poor-quality diets,

alcoholics and individuals on certain medications or with certain diseases. [WHO; Environ Health Criteria 196: Methanol p.113 (1997). Available from, as of July 19, 2005: http://www.inchem.org/documents/ehc/ehc/ehc196.htm] **PEER REVIEWED**

It has been suggested that the metabolic acidosis due to methanol might be

exacerbated in individuals with diabetes since it is well known that these patients suffer from diabetic ketoacidosis. However, there are no clinical or experimental data on any interaction between methanol acidosis and diabetic ketoacidosis. [WHO; Environ Health Criteria 196: Methanol p.113 (1997). Available from, as of July 19, 2005: http://www.inchem.org/documents/ehc/ehc/ehc196.htm] **PEER REVIEWED**

PROBABLE ROUTES OF HUMAN EXPOSURE:

STUDY OF WOOD HEEL INDUSTRY IN MA SHOWED AVG METHANOL VAPOR CONCN RANGING FROM 160-170 PPM, WITH NO DEFINITE EVIDENCE OF INJURY TO EXPOSED WORKERS ... CONCN BETWEEN 400 & 1000 PPM IN SPIRIT DUPLICATING PROCESSES /WERE REPORTED/. NO MENTION WAS MADE OF SYMPTOMS OR COMPLAINTS, BUT THESE CONCN WERE CONSIDERED EXCESSIVE. ... [American Conference of Governmental Industrial Hygienists. Documentation of the Threshold Limit Values and Biological Exposure Indices. 5th ed. Cincinnati, OH: American Conference of Governmental Industrial Hygienists, 1986., p. 372] **PEER REVIEWED**

ALTHOUGH INDIVIDUAL RESPONSES OF MAN TO METHYL ALCOHOL MAY VARY

CONSIDERABLY, INDUSTRIAL EXPOSURES ARE NOT VERY HAZARDOUS IF CONCN ARE MAINTAINED WITHIN UPPER LIMIT OF 200 PPM BY PROPER VENTILATION. [Clayton, G. D. and F. E. Clayton (eds.). Patty's Industrial Hygiene and Toxicology: Volume 2A, 2B, 2C: Toxicology. 3rd ed. New York: John Wiley Sons, 1981-1982., p. 4541] **PEER REVIEWED**

NIOSH (NOES Survey 1981-1983) has statistically estimated that 1,219,371 workers (295,849 of these are female) are potentially exposed to methanol in the US(1). Occupational exposure to methanol may occur through inhalation and dermal contact with this compound at workplaces where methanol is produced or used(SRC). Monitoring data indicate that the general population may be exposed to methanol via inhalation of ambient air, ingestion of food and drinking water(SRC). [(1) NIOSH; International Safety Cards. Methanol. 67-56-1. Available at http://www.cdc.gov/niosh/ipcs/nicstart.html as of Jul 1, 2005.] **PEER

REVIEWED**

BODY BURDEN: Methanol was detected in 1 of 12 samples of human milk collected from volunteers in 4 USA cities(1). Methanol has been detected in expired human air(2,3,4); in one study, it was detected in 3.6% of 387 expired air samples collected from 54 volunteers at a geometric mean concn of 0.549 ng/l(4). [(1) Pellizzari ED et al; Bull Environ Contam Toxicol 28: 322-8 (1982) (2) Krotosynski B; J Chromat Sci 15: 239-44 (1977) (3) Krotosynski BK, O'Neill HJ; J Environ Sci Health Part A-Environ Sci Eng 17: 855-83 (1982) (4) Krotosynski BK et al; J Anal Toxicol 3: 255-43 (1979)] **PEER

REVIEWED**

MINIMUM FATAL DOSE LEVEL: The minimum lethal dose of methanol in the absence of medical treatment is between 0.3 and 1 g/kg. [Environmental Health Criteria 196: Methanol pp. 8 (1997) by the International Programme on Chemical Safety (IPCS) under the joint sponsorship of the United Nations Environment Programme, the International Labour Organisation and the World Health Organization.]

**PEER REVIEWED**

EMERGENCY MEDICAL TREATMENT: 

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2/24/2011 htt p ://toxnet.nlm.nih. g ov/c g i- b in/sis/download.txtEMERGENCY MEDICAL TREATMENT:

EMT COPYRIGHT DISCLAIMER: Portions of the POISINDEX(R) and MEDITEXT(R) database have been provided here for general reference. THE COMPLETE POISINDEX(R) DATABASE OR MEDITEXT(R)

DATABASE SHOULD BE CONSULTED FOR ASSISTANCE IN THE DIAGNOSIS OR TREATMENT OF SPECIFIC CASES. The use of the POISINDEX(R) and MEDITEXT(R) databases is at your sole risk. The POISINDEX(R) and MEDITEXT(R) databases are provided "AS IS" and "as available" for use, without warranties of any kind, either expressed or implied. Micromedex makes no representation or warranty as to the accuracy, reliability, timeliness, usefulness or completeness of any of the information contained in the POISINDEX(R) and MEDITEXT(R) databases. ALL IMPLIED WARRANTIES

OF MERCHANTABILITY AND FITNESS FOR A PARTICULAR PURPOSE OR USE ARE HEREBY EXCLUDED. Micromedex does not assume any responsibility or risk for your use of the POISINDEX(R) or MEDITEXT(R) databases. Copyright 1974-2011 Thomson MICROMEDEX. All Rights Reserved. Any duplication, replication, "downloading," sale, redistribution or other use for commercial purposes is a violation of Micromedex' rights and is strictly prohibited.<p>The following Overview, *** METHANOL ***, is relevant for this HSDB record chemical.

LIFE SUPPORT: o This overview assumes that basic life support measures

have been instituted.

CLINICAL EFFECTS:

0.2.1 SUMMARY OF EXPOSURE

0.2.1.1 ACUTE EXPOSURE A) USES: One of the toxic alcohols that is found in windshield wiper fluid, gas line antifreeze, fuels, photocopy fluid, solvents, carburetor cleaner, and as

an adulterant in homemade ethanol distillates. B) TOXICOLOGY: An alcohol that causes intoxication similar to ethanol and is metabolized to formaldehyde and formic acid via alcohol dehydrogenase and aldehyde dehydrogenase, respectively. Formic acid causes a metabolic acidosis and causes blindness through direct retinal toxicity. Toxicity is most common after ingestion but has been reported with inhalation and dermal exposures. C) EPIDEMIOLOGY: Uncommon exposure that can result in significant morbidity and mortality. D) WITH POISONING/EXPOSURE 1) MILD TO MODERATE TOXICITY: Patients will initially have signs of acute intoxication, such as ataxia, sedation, and disinhibition. Patients may also complain of abdominal pain, nausea, vomiting, and headache. Acidosis or signs of visual impairment suggest a more severe poisoning. 2) SEVERE TOXICITY: Severe metabolic acidosis develops hours after exposure (if ethanol is not coingested) and may lead to multiorgan dysfunction including hypotension, tachycardia, dysrhythmias, seizures, coma, and pancreatitis. In addition, ocular toxicity may develop; manifestations include mydriasis, hyperemic optic discs, and papilledema. Visual impairment may develop, which may range from blurry/hazy vision to color vision defects to

"snowfield" vision to total blindness. Permanent sequelae after severe intoxication may include basal ganglia necrosis with parkinsonian features (ie, tremor, rigidity, bradykinesia) and blindness.

0.2.3 VITAL SIGNS

0.2.4 HEENT

0.2.4.1 ACUTE EXPOSURE A) WITH POISONING/EXPOSURE 1) Blurred or double vision, constricted visual fields, spots before the eyes, sharply reduced visual acuity, optic atrophy, blindness, nystagmus, and whiteness in the visual field have been described. Fixed, dilated pupils suggest severe poisoning. a) Onset of effects may be delayed for 12 to 24 hours. Fundoscopic findings may be normal or may show peripapillary edema, hyperemia of the optic disc, or

retinal edema.

0.2.5 CARDIOVASCULAR

0.2.5.1 ACUTE EXPOSURE A) WITH POISONING/EXPOSURE 1) Tachycardia is fairly common; bradycardia may develop in fatal poisonings. Cardiac failure and severe hypotension may occur.

0.2.6 RESPIRATORY

0.2.6.1 ACUTE EXPOSURE A) WITH POISONING/EXPOSURE 1) Tachypnea from metabolic acidosis is common. Sudden respiratory failure may occur in the terminal stages.

0.2.7 NEUROLOGIC

0.2.7.1 ACUTE EXPOSURE A) WITH POISONING/EXPOSURE 1) Seizures, coma, and symptoms similar to ethanol "hangover" may occur. 2) Permanent sequelae may include basal ganglia infarcts, parkinsonism, toxic encephalopathy, polyneuropathy, optic atrophy, and blindness. 

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2/24/2011 htt p ://toxnet.nlm.nih. g ov/c g i- b in/sis/download.txt0.2.8 GASTROINTESTINAL

0.2.8.1 ACUTE EXPOSURE A) WITH POISONING/EXPOSURE 1) Abdominal pain, anorexia, nausea, and vomiting may occur. In severe poisonings, acute necrotizing pancreatitis has been reported.

0.2.10 GENITOURINARY

0.2.10.1 ACUTE EXPOSURE A) WITH POISONING/EXPOSURE 1) Acute renal failure and hematuria have been reported.

0.2.11 ACID-BASE

0.2.11.1 ACUTE EXPOSURE A) Metabolic acidosis is classic. Concurrent ethanol ingestion may delay acidosis for 18 to 24 hours or longer.

0.2.12 FLUID-ELECTROLYTE

0.2.12.1 ACUTE EXPOSURE A) WITH POISONING/EXPOSURE 1) Hypomagnesemia, hypokalemia, and hypophosphatemia have been reported.

0.2.15 MUSCULOSKELETAL

0.2.15.1 ACUTE EXPOSURE A) WITH POISONING/EXPOSURE 1) Rhabdomyolysis may occur in severe poisonings.

0.2.20 REPRODUCTIVE HAZARDS A) Methanol, together with other solvents, has been linked with birth defects of the central nervous system in humans (Holmberg, 1979), but methanol cannot be considered a human reproductive hazard, because of mixed or poorly documented exposures.

0.2.21 CARCINOGENICITY

0.2.21.1 IARC CATEGORY A) IARC Carcinogenicity Ratings for CAS67-56-1 (IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2006; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2007; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2010; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2010a; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2008; IARC, 2004): 1) Not Listed

LABORATORY: A) Monitor mental status, vital signs, and ECG. B) In patients with significant CNS depression or metabolic acidosis, obtain arterial or venous blood gases. C) Obtain a serum methanol and ethanol concentration and serial serum electrolytes; calculate anion gap. D) If serum methanol cannot be obtained in a timely fashion, measure serum osmolality and calculate osmolal gap. The osmolal gap is equal to the measured serum osmolality minus (2 x serum sodium + BUN/2.8) + glucose/18 + ethanol/4.6). An elevated osmolal gap (greater than 10) suggests the presence of toxic alcohols, but a normal osmolal gap does NOT rule this out.

TREATMENT OVERVIEW:

0.4.2 ORAL EXPOSURE A) MANAGEMENT OF MILD TO MODERATE TOXICITY 1) Obtain a methanol level, serum chemistry, and a serum pH. A thorough visual exam should be performed, including visual acuity. An elevated osmolar gap suggests the presence of methanol or another alcohol but cannot be used to rule out a significant exposure. If a methanol concentration is readily available (results known within 2 hours) and the patient is asymptomatic, then alcohol dehydrogenase (ADH) inhibition can be delayed until the methanol

concentration is available. Patients with a methanol concentration of more than 25 mg/dL or metabolic

acidosis should be treated with ADH inhibition. If methanol concentrations cannot readily be measured, patients with a history of a potentially toxic ingestion, symptomatic patients, and those with suspected methanol intoxication with an anion gap metabolic acidosis or an osmolal gap greater than 10

mOsm should be treated with ADH inhibition. Folate should also be intravenously administered to patients requiring ADH inhibition. In patients who receive ADH inhibition who have a significant methanol concentration, consider hemodialysis since the apparent

half-life of methanol under these circumstances is quite prolonged. B) MANAGEMENT OF SEVERE TOXICITY 1) Patients presenting with severe acidosis, signs or symptoms of visual changes, or depressed level of consciousness should be started immediately on an ADH inhibitor and intravenous folate. Hemodialysis should

be initiated and should be continued until the methanol concentration is undetectable and the serum pH is normal. Treat seizures with benzodiazepines.

C) DECONTAMINATION 

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2/24/2011 htt p ://toxnet.nlm.nih. g ov/c g i- b in/sis/download.txt1) PREHOSPITAL: There is no role for prehospital

decontamination. 2) HOSPITAL: In general, gastrointestinal decontamination is not very useful because methanol is rapidly absorbed and binds poorly to activated charcoal. Insertion of a nasogastric tube to aspirate gastric contents may be useful in rare patients who present shortly after large ingestions. D) AIRWAY MANAGEMENT 1) Endotracheal intubation may be necessary in patients with significant CNS or respiratory depression. Extreme

care must be taken to increase minute ventilation sufficiently to prevent severe acidemia in intubated patients.

E) ANTIDOTE 1) Treat patients with either ethanol or fomepizole (4-methylpyrazole) to prevent the production of formate. Indications include documented plasma methanol concentration greater than 20 mg/dL (greater than 200 mg/L) OR documented recent history of ingesting toxic amounts of methanol and osmolal gap greater than 10 mOsm/L OR history or strong clinical suspicion of methanol poisoning with at least 2 of the following criterion: arterial pH less than 7.3; serum bicarbonate less than 20 mEq/L; osmolol gap greater than 10 mOsm/L. a) ETHANOL VS FOMEPIZOLE: Fomepizole is easier to use clinically, requires less monitoring, does not cause CNS depression or hypoglycemia, and may obviate the need for dialysis in some patients. Ethanol requires continuous administration and frequent monitoring of serum ethanol and glucose levels and may cause CNS depression and hypoglycemia (especially in children). The drug cost associated with ethanol use is generally much lower than with fomepizole; however, other costs associated with ethanol use (eg, continuous intravenous infusion, hourly blood draws, nursing costs, and ethanol levels, possibly greater use of hemodialysis) may make the costs more comparable. b) ETHANOL: Ethanol is given to maintain a serum ethanol concentration of 100 to 150 mg/dL. This can be accomplished by using a 5% or 10% ethanol solution administered intravenously through a central line. Intravenous therapy dosing, which is preferred, is 0.8 g/kg as a loading dose (8 mL/kg of 10% ethanol) administered over 20 to 60 minutes as tolerated, followed by an infusion rate of 80 to 150 mg/kg/hr (for 10% ethanol, 0.8 to 1.3 mL/kg/hr for a nondrinker; 1.5 mL/kg/hr for a chronic alcoholic). During hemodialysis, either add ethanol to the dialysate to achieve 100 mg/dL concentration or increase the rate of infusion during dialysis (10% ethanol, 2.5 to 3.5 mL/kg/hr). Oral ethanol may be used as a temporizing measure until intravenous ethanol or fomepizole can be obtained, but it is more

difficult to achieve the desired stable ethanol concentration. The loading dose is 0.8 g/kg (4 mL/kg) of 20% {40 proof}) ethanol diluted in juice administered orally or via nasogastric tube. Maintenance dose is 80 to 150 mg/kg/hr (20% {40 proof}) ethanol; 0.4 to 0.7 mL/kg/hr for a nondrinker; 0.8 mL/kg/hr for a chronic alcoholic). Concentrations greater than 30% (60 proof) ethanol should be diluted. For both modalities, blood ethanol levels must be monitored hourly and adjusted accordingly, and both require patient monitoring in an ICU setting. c) FOMEPIZOLE: Fomepizole is administered as a 15 mg/kg loading dose, followed by 4 bolus doses of 10 mg/kg every 12 hours. If therapy is needed beyond this 48-hour period, the dose is then increased to 15 mg/kg every 12 hours for as long as necessary. Fomepizole is also effectively removed by hemodialysis; therefore, doses should be repeated following each round of hemodialysis. d) FOLATE: Folate increases clearance of formate. Administer 50 mg every 4 hours to any patient requiring ADH inhibition.

F) ENHANCED ELIMINATION 1) Methanol and its metabolites (formaldehyde and formic acid) are readily removed by hemodialysis. Emergent hemodialysis is indicated in any methanol-intoxicated patient with an anion gap metabolic acidosis (pH less than 7.3), visual disturbances, or CNS depression. Because methanol is cleared very slowly once ADH inhibitors are administered, hemodialysis should also be considered in patients with methanol concentrations greater than 50 mEq/L, even in the absence of acidosis

or severe symptoms. G) PATIENT DISPOSITION 1) OBSERVATION CRITERIA: Intentional ingestions should be evaluated in a health care facility. Potential serum levels can be calculated using methanol percentage, 

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2/24/2011 htt p ://toxnet.nlm.nih. g ov/c g i- b in/sis/download.txtamount ingested, and patient weight and all levels potentially greater than 25 mg/dL should be evaluated in a health care facility. 2) ADMISSION CRITERIA: Patients who are acidotic, have visual symptoms, or have serum methanol concentrations above 25 mg/dL should be admitted. 3) CONSULT CRITERIA: Consult a poison center or medical toxicologist in cases of severe poisonings, in cases where a methanol level is not readily available, or in cases where the ingestion is uncertain. Consult a nephrologist for any patient who may require hemodialysis. H) PITFALLS 1) Depending on the timing of the presentation, an increased osmolar gap or an increased anion gap may not always be present. An increased anion gap will not be present in patients presenting early, and an increased osmol gap may not be present in patients presenting late. When calculating osmolarity, the ethanol level

needs to be taken into account in the calculation. A normal osmolal gap does not rule out the possibility of

methanol intoxication. Patients who are ethanol intoxicated will have a later presentation of their acidosis, as the ethanol is effectively blocking the

metabolism of the methanol.

I) PHARMACOKINETICS 1) Methanol is rapidly and readily absorbed. The apparent half-life of methanol is approximately 8 to 28 hours. The volume of distribution is approximately 0.6 L/kg. It is not protein bound.

J) TOXICOKINETICS 1) When alcohol dehydrogenase inhibitors are being used, the apparent half-life is increased to approximately 50

hours. K) DIFFERENTIAL DIAGNOSIS 1) Exposure to other alcohols, such as ethanol, ethylene glycol, isopropyl alcohol, and other glycol ethers. A broad variety of other toxins and medical causes can

also result in a metabolic acidosis.

0.4.3 INHALATION EXPOSURE A) Intentional inhalational exposures can result in significant methanol levels and should be treated similarly to oral ingestions. B) INHALATION: Move patient to fresh air. Monitor for respiratory distress. If cough or difficulty breathing develops, evaluate for respiratory tract irritation, bronchitis, or pneumonitis. Administer oxygen and assist ventilation as required. Treat bronchospasm with inhaled beta2 agonist and oral or parenteral corticosteroids.

0.4.4 EYE EXPOSURE A) DECONTAMINATION: Irrigate exposed eyes with copious amounts of room temperature water for at least 15 minutes. If irritation, pain, swelling, lacrimation, or photophobia persist, the patient should be seen in a health care facility.

0.4.5 DERMAL EXPOSURE A) OVERVIEW 1) Rarely has repeated dermal exposure resulted in severe methanol toxicity. It should be treated similarly to an ingestion exposure. 2) DECONTAMINATION: Remove contaminated clothing and wash exposed area thoroughly with soap and water. A physician may need to examine the area if irritation or pain persists.

RANGE OF TOXICITY: A) TOXICITY: Most experts agree that a methanol concentration of 25 mg/dL is the threshold for treatment. An ingestion of 0.25 mL/kg of 100% methanol would theoretically (assuming 100% absorption) result in a

toxic methanol concentration.

ANTIDOTE AND EMERGENCY TREATMENT: The drug 4-methylpyrazole (4-MP; fomepizole) is a competitive ADH inhibitor and an effective antidote for methanol and ethylene glycol poisoning. The concentration at which 4-MP inhibits 50% of ADH is 0.1 umol/L. The drug is used iv and orally and is eliminated by Michaelis-Menten kinetics. [Sullivan, J.B., Krieger G.R. (eds). Clinical Environmental Health and Toxic Exposures. Second edition. Lippincott Williams and Wilkins, Philadelphia, Pennsylvania 1999., p. 1179] **PEER

REVIEWED**

Although clinical data are limited, folate or folinic acid (leucovorin, citrovorum factor) commonly is given during the first 24 hours and is

believed to hasten formate metabolism to carbon dioxide and water. [Sullivan, J.B., Krieger G.R. (eds). Clinical Environmental Health and Toxic Exposures. Second edition. Lippincott Williams and Wilkins, Philadelphia, Pennsylvania 1999., p. 1179] **PEER REVIEWED**

Sodium bicarbonate has two important roles in treating toxic alcohol ingestions. As an immediate temporizing measure, administration of sodium bicarbonate may reverse the life-threatening acidemia associated with 

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2/24/2011 htt p ://toxnet.nlm.nih. g ov/c g i- b in/sis/download.txtmethanol... ingestions. ...The second role for bicarbonate in the treatment of toxic alcohol poisoning involves its ability to favorably

alter the distribution and elimination of certain toxic metabolites. In cases of methanol poisoning, the proportion of ionized formic acid can be increased by administering bicarbonate, thereby trapping formate in the blood compartment. Consequently, decreased visual toxicity may result from the removal of the toxic metabolites for the optic nerve. ...Further investigation is required to delineate the beneficial effects of sodium bicarbonate in the treatment of toxic alcohol ingestions. [Goldfrank, L.R. (ed). Goldfrank's Toxicologic Emergencies. 7th Edition McGraw-Hill New York, New York 2002., p. 523] **PEER REVIEWED**

...Fomepizole, administered early in ethylene glycol (EG) intoxication, prevents renal injury. In the absence of renal failure, EG clearance is rapid, avoiding the need for prolonged fomepizole administration. The long elimination half-life of methanol poisonings, with absent hemodialysis, necessitates prolonged administration of fomepizole. ... However, EG-poisoned patients treated with fomepizole prior to the onset of significant acidosis may not require hemodialysis. Indeed, fomepizole may also obviate the need for hemodialysis in selected methanol-poisoned patients, in the absence of neurological and ocular impairment or severe acidosis. ... [Megarbane B et al; Intensive Care Med 31 (2): 189-95 (2004)] **PEER REVIEWED** <a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15627163&query_hl=52" target=new>PubMed Abstract

Basic treatment: Establish a patent airway. Suction if necessary. Watch for signs of respiratory insufficiency and assist ventilations if necessary. Administer oxygen by nonrebreather mask at 10 to 15 L/min. Monitor for shock and treat if necessary ... . Anticipate seizures and minimize all external stimuli. Treat seizures if necessary ... . For eye contamination, flush eyes immediately with water. Irrigate each eye continuously with normal saline during transport ... . Do not use emetics. For ingestion, rinse mouth and administer 5 ml/kg up to 200 ml of water for dilution if the patient can swallow, has a strong gag reflex, and does not drool. Administer activated charcoal ... . /Methyl Alcohol and Related Compounds/ [Bronstein, A.C., P.L. Currance; Emergency Care for Hazardous Materials Exposure. 2nd ed. St. Louis, MO. Mosby Lifeline. 1994., p. 203-4] **PEER REVIEWED**

Advanced treatment: Consider orotracheal or nasotracheal intubation for airway control in the patient who is unconscious or in respiratory arrest. Start an IV with lactated Ringer's to support vital signs. Watch for signs of fluid overload. Treat seizures with diazepam ... . For hypotension with signs of hypovolemia, administer fluid cautiously. Watch for signs of fluid overload ... . Hyperventilation may be beneficial for treating acidosis. Use proparacaine hydrochloride to assist eye irrigation ... . /Methyl Alcohol and Related Compounds/ [Bronstein, A.C., P.L. Currance; Emergency Care for Hazardous Materials Exposure. 2nd ed. St. Louis, MO. Mosby Lifeline. 1994., p. 204] **PEER REVIEWED**

Emergency and supportive measures. 1. Maintain ann open airway and assist ventilation if necessary. 2. Treat coma and seizures if they occur. 3.

Treat metabolic acidosis with iv sodium bicarbonate. Correction of acidosis should be guided by arterial blood gases. [Olson, K.R. (Ed.); Poisoning & Drug Overdose. 4th ed. Lange Medical Books/McGraw-Hill. New York, N.Y. 2004., p. 261] **PEER REVIEWED**

Specific drugs and antidotes. 1. Administer fomepizole or ethanol to saturate the enzyme alcohol dehydrogenase and prevent the formation of methanol's toxic metabolites. Therapy is indicated in patients with the following: a. A history of significant methanol ingestion, when methanol serum levels are not immediately available and the osmolar gap is > 10 mOsm/L. b. Metabolic acidosis and an osmolar gap > 10 mOsm/L not accounted for by ethanol. c. A methanol blood concentration > 20 mg/dL. 2. Folic or folinic acid may enhance the conversion of formate to carbon dioxide and water. [Olson, K.R. (Ed.); Poisoning & Drug Overdose. 4th ed. Lange Medical Books/McGraw-Hill. New York, N.Y. 2004., p. 261]

**PEER REVIEWED**

Decontamination. 1. Prehospital. Do not induce vomiting or administer charcoal. 2. Hospital. Aspirate gastric contents if this can be performed within 30-60 min of ingestion. Activated charcoal is not likely to be useful because the effective dose is very large and methanol is rapidly absorbed from the GI tract. [Olson, K.R. (Ed.); Poisoning & Drug Overdose. 4th ed. Lange Medical Books/McGraw-Hill. New York, N.Y. 2004., p. 261] **PEER REVIEWED**

Enhanced elimination. Hemodialysis rapidly removes both methanol (half-life reduced to 3-6 hr) and formate. The indication for dialysis are suspected methanol poisoning with significant metabolic acidosis, visual abnormalities, an osmolar gap > 10 mOsm/L, or a measured serum methanol concentration > 50 mg/dL. Dialysis should be continued until the methanol concentration is < 20 mg/dL. [Olson, K.R. (Ed.); Poisoning & Drug Overdose. 4th ed. Lange Medical Books/McGraw-Hill. New York, N.Y. 2004., p. 261] **PEER REVIEWED**

ANIMAL TOXICITY STUDIES: 

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2/24/2011 htt p ://toxnet.nlm.nih. g ov/c g i- b in/sis/download.txtTOXICITY SUMMARY: Methanol occurs naturally in humans, animals and plants. It is a natural constituent in blood, urine, saliva and expired air. ... The two most important sources of background body burdens for methanol and formate are diet and metabolic processes. Methanol is available in the diet principally from fresh fruits and vegetables, fruit juices ... fermented beverages ... and diet foods (principally soft drinks). The artificial sweetner aspartame is widely used and, on hydrolysis, 10% (by weight) of the molecule is converted to free methanol, which is available for absorption. ... Exposures to methanol can occur in occupational settings through inhalation or dermal contact. ... Methanol is readily absorbed by inhalation, ingestion and dermal exposure, and it is rapidly distributed to tissues according to the distribution of body water. A small amount of methanol is excreted unchanged by the lungs and kidneys. ... Methanol is metabolized primarily in the liver by sequential oxidative steps to formaldehyde, formic acid and carbon dioxide. The initial step involves oxidation to formaldehyde by hepatic alcohol dehydrogenase ... In step 2, formaldehyde is oxidized by formaldehyde dehydrogenase to formic acid/or formate depending on the pH. In step 3, formic acid is detoxified to carbon dioxide by folate-dependent reactions. Elimination of methanol from the blood via the urine and exhaled air and by metabolism appears to be slow in all species, especially when compared to ethanol. ... It is the rate of metabolic detoxification, or removal of formate that 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, etc.) are usually the cause of death. Sensitive primate species (humans and monkeys) develop increased blood formate concentrations following methanol exposure, while resistant rodents, rabbits and dogs do not. Humans and non-human primates are uniquely sensitive to the toxic effects of methanol. 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 ... There is no evidence from animal studies to suggest that methanol is a carcinogen ... 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 ... There was increased embryo/fetal death ... and an increasing incidence of full litter resorptions. Reduced fetal weight

was observed ... Fetal malformations ... included neural and ocular defects, cleft palate, hydronephrosis and limb anomalies. Humans (and non-human primates) are uniquely sensitive to methanol poisoning and the toxic effects in these species are characterized by formic acidemia, metabolic acidosis, ocular toxicity, nervous system depression, blindness, coma and death. 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. Although ingestion dominates as the most frequent route of poisoning, inhalation of high concentrations of methanol vapor and percutaneous absorption of methanolic liquids are as effective as the oral route in producing acute toxic effects. The most noted health consequences of longer term exposure to lower levels of methanol is a broad range of ocular effects. ... The toxicity is manifest if formate generation

continues at a rate that exceeds its rate of metabolism. ... The minimum

lethal dose of methanol in the absence of medical treatment is between 0.3 and 1 g/kg. The minimum dose causing permanent visual defects is unknown. ... 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. The acidosis is largely attributed to the formic acid produced when methanol is metabolized. ... Visual disturbances of several types (blurring, constriction of the visible field, changes in color perception, and temporary or permanent blindness) have been reported in workers ... No other adverse effects of methanol have been reported in humans except minor skin and eye irritation. ... 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. [Environmental Health Criteria 196: Methanol pp. 1-9 (1997) by the International Programme on Chemical Safety (IPCS) under the joint sponsorship of the United Nations Environment Programme, the International Labour Organisation and the World Health Organization.] **PEER REVIEWED**

NON-HUMAN TOXICITY EXCERPTS: /LABORATORY ANIMALS: Acute Exposure/ Under acute inhalation conditions, 

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2/24/2011 htt p ://toxnet.nlm.nih. g ov/c g i- b in/sis/download.txtfolate-deficient Long-Evans male rats exposed to 4000 mg/cu m (3000 ppm) methanol for 20 hr/day did not survive more than 4 days. Rhesus monkeys exposed to 4000 mg/cu m (3000 ppm) methanol for 21 hr/day survived the 20-day exposure period and rhesus monkeys exposed to 13,000 mg/cu m (10,000 ppm) methanol for 21 hr/day survived for more than 4 days. [WHO; Environ Health Criteria 196: Methanol p.10 (1997). Available from, as of July 14, 2005: http://www.inchem.org/documents/ehc/ehc/ehc196.htm] **PEER

REVIEWED**

/LABORATORY ANIMALS: Acute Exposure/ Oxygen free radicals are generated during methanol-induced liver injury, as was shown for ethanol. The effect of methanol intoxication (6 g/kg bw) on protein modification in the liver of rats was investigated. Electron spin resonance determination indicated an increase in the free radical signal 6 and 12 hr after intoxication. After 7 days of treatment, the contents of malondialdehyde and carbonyl groups in proteins were significantly increased. The level of amino groups and sulphydryl groups and the amount of tryptophan in proteins were decreased, whereas the amount of bi-tyrosine was increased significantly. Changes in protein structure resulted both from free radical action and formaldehyde generation during methanol intoxication. [Skrzydlewska E et al; J Appl Toxicol 20 (3): 239-43 (2000)] **PEER REVIEWED** <a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=10797478&query_hl=42" target=new>PubMed Abstract

/LABORATORY ANIMALS: Acute Exposure/ An approximate intraperitoneal methanol LD50 of 3-4 g/kg for pigtail monkeys (Macaca nemestrina) was reported... . Doses of 2 and 3 g/kg produced metabolic acidosis in the animals, while monkeys given 4 g/kg became severely acidotic and exhibited signs of toxicity that were remarkably similar to those reported in human poisoning. These animals displayed a sharp decrease in blood pH (7.03) at 7.5-21 hr after methanol administration. Bicarbonate was the single blood electrolyte observed to change during the course of methanol acidosis. There was a latent period of 15-18 hr prior to the onset of overt signs of toxicity, followed by a sequence of signs beginning with behavioral distress, coma within 24-30 hr and death. This time-course parallels that reported for humans suffering from methanol poisoning. [WHO; Environ Health Criteria 196: Methanol p.78 (1997). Available from, as of July 18, 2005: http://www.inchem.org/documents/ehc/ehc/ehc196.htm] **PEER

REVIEWED**

/LABORATORY ANIMALS: Acute Exposure/ Methanol is irritating to the eye and causes conjunctivitis, chemosis, iritis, and corneal opacity. Methanol was reported to be a mild eye irritant. However, in another study, undiluted methanol caused moderate corneal opacity in three of six rabbits and conjunctival redness in all six rabbits. A 50% aqueous methanol solution caused minimal to no effects, and a 25% aqueous solution caused no effects. [Bingham, E.; Cohrssen, B.; Powell, C.H.; Patty's Toxicology Volumes 1-9 5th ed. John Wiley & Sons. New York, N.Y. (2001)., p. V6 p.372] **PEER REVIEWED**

/LABORATORY ANIMALS: Acute Exposure/ In a sensory irritation test, methanol produced sensory irritation in mice at very high vapor concentrations with a RD50 (concentration that decreases respiration rate by 50%) of 25,300 ppm and 41,514. [Bingham, E.; Cohrssen, B.; Powell, C.H.; Patty's Toxicology Volumes 1-9 5th ed. John Wiley & Sons. New York, N.Y. (2001)., p. V6 p.372] **PEER REVIEWED**

/LABORATORY ANIMALS: Acute Exposure/ Its consumption leads to atrophy of the optic nerve, causing permanent blindness, and to depression of cardiac and voluntary muscle, resulting in death. [Garner's Veterinary Toxicology. 3rd ed., rev. by E.G.C. Clarke and M.L. Clarke. Baltimore: Williams and Wilkins, 1967., p. 285] **PEER REVIEWED**

/LABORATORY ANIMALS: Acute Exposure/ Exposure of animals /to methanol in air/ ... may induce ... increased rate of respiration ... nervous depression followed by excitation, irritation of mucous membranes, ataxia, partial paralysis, agony, prostration, CNS depression, convulsions, decrease in rectal temperature, loss in weight and death. [Bingham, E.; Cohrssen, B.; Powell, C.H.; Patty's Toxicology Volumes 1-9 5th ed. John Wiley & Sons. New York, N.Y. (2001)., p. V6 p.372] **PEER REVIEWED**

/LABORATORY ANIMALS: Acute Exposure/ The pathologic changes found in the tissues of animals exposed by inhalation to methyl alcohol are quite similar to those observed in animals following ingestion of this compound. In the eyes of the dog ... hyperemia of the choroid and edema of the ocular tissue with early signs of degeneration of the ganglionic cells of the retina and nerve fibers /were found/ ... Vessels of the choroid of poisoned animals were markedly congested, the entire retina was edematous, and the ganglion cells were degenerated. ... Hemorrhage, edema, congestion, and pneumonia were observed in the lung of the various species that were exposed to vapors containing methyl alcohol. The livers and kidneys showed congestion, albuminous and fatty degeneration and fatty infiltration. Cardiac dilation and myocardial degeneration were observed in the hearts of animals. Degenerative injuries of the central nervous system have been described ... . [Clayton, G. D. and F. E. Clayton (eds.). Patty's Industrial Hygiene and Toxicology: Volume 2A, 2B, 2C: Toxicology. 3rd ed. New York: John Wiley Sons, 1981-1982., p. 4531] **PEER REVIEWED**

/LABORATORY ANIMALS: Acute Exposure/ Within 48 hr of administering a single LD50 dose to rats, brain enzyme activities underwent changes, glycogen levels increased, brain lactic acid levels increased 1 hr after 

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2/24/2011 htt p ://toxnet.nlm.nih. g ov/c g i- b in/sis/download.txtadministration, decreased 48 hr after. [Mikulich SG; Biol Akt Veshchestva (Mikroelem, Vitam Drugie) Rastenievod Zhivotnovod Med 109-11 (1975)]

**PEER REVIEWED**

/LABORATORY ANIMALS: Acute Exposure/ After methanol administration, Macaca mulatta showed optic edema, acidosis, and formate accumulation in blood. [Martin-Amat et al; Toxicol Appl Pharmacol 45 (1): 201-8 (1978)] **PEER

REVIEWED** <a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=99844" target=new>PubMed Abstract

/LABORATORY ANIMALS: Acute Exposure/ The effects of alcohol on audition were studied in the rat by examining the modification of acoustic startle reflexes by pure tone pulses and by gaps in white noise. Groups of rats received four injections of 0.0, 0.25, 1, and 2 g/kg of either methyl or ethyl alcohol in increasing order at 1 hr intervals. One-half hour after the administration of each dose, loudness perception or temporal acuity was measured. Blood alcohol levels (mM) for the two alcohols obtained in control animals were equivalent following the final dose. Both alcohols produced a dose dependent reduction in baseline startle amplitude that was greater during exposure to ethanol than methanol. Loudness functions associated with pulse intensity were not diminished by the alcohols, however inhibition produced by a gap in noise was reduced following the highest dose of either alcohol. These data are consistent with behavioral study results that have suggested that alcohol does not affect loudness perception, and with electrophysical experiment results which indicate that alcohol disrupts temporal relationships along the primary auditory pathway. [Wecker JR, Ison JR; Toxicol Appl Pharm 74 (2): 258-66 (1984)]

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/LABORATORY ANIMALS: Acute Exposure/ The results of the skin absorption experiments were described by stating that all animals subjected to the action of any amount of methyl alcohol by skin absorption had died. The lowest lethal dose was 0.5 mL/kg for one monkey. It was reported that rabbits were far less susceptible to methyl alcohol poisoning by this route than monkeys and rats. In a study of the effects of continuous administration of methyl alcohol, a known amount was dropped onto or injected into the gauze pads 4 times/day. All such treated monkeys displayed dilated pupils within 2 hr after one such administration of 1.3 mg/kg of methyl alcohol. The minimum lethal dose was a total of 4 administrations of 0.5 mL/kg methyl alcohol in one day, and it was concluded that sufficient methyl alcohol could be absorbed through the skin to cause death and that the threshold for immediate danger in monkeys was below the minimum lethal dose. [McCord CP; Ind Eng Chem 23: 931-6 (1931) as cited in NIOSH; Criteria Document: Methyl Alcohol p.59-60 (1976) DHEW Pub. NIOSH 76-148] **PEER REVIEWED**

/LABORATORY ANIMALS: Acute Exposure/ Methanol administered by gavage or intraperitoneally induced hypothermia in Fischer and Long-Evans rats, eg, brain temperature decreased 1.5 deg C within 35 min and colonic temperature was significantly lower. This occurred at dose levels of 2-3 g/kg, which is about 20% of the reported LD50 value of 10 g/kg in rats. [WHO; Environ Health Criteria 196: Methanol p.74 (1997). Available from, as of July 14, 2005: http://www.inchem.org/documents/ehc/ehc/ehc196.htm]

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/LABORATORY ANIMALS: Acute Exposure/ Female minipigs (Minipig YU, Charles River) treated with a single oral dose of methanol at 1, 2.5 and 5.0 g/kg body weight by gavage showed dose-dependent signs of acute methanol intoxication, including mild CNS depression, tremors, ataxia and recumbency, which developed within 0.5-2.0 hr and resolved by 52 hr. Methanol- and formate-dosed minipigs did not develop optic nerve lesions, toxicologically significant formate accumulation or metabolic acidosis. [WHO; Environ Health Criteria 196: Methanol p.10 (1997). Available from, as of July 14, 2005: http://www.inchem.org/documents/ehc/ehc/ehc196.htm]

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/LABORATORY ANIMALS: Subchronic or Prechronic Exposure/ Rats received 3.25 mL methanol/kg bw for 6 months. The treatment caused a decline in the heart contraction rate and in skin temperature by the end of the experiment. Myocardial hypoxia developed. [Sheftel, V.O.; Indirect Food Additives and Polymers. Migration and Toxicology. Lewis Publishers, Boca Raton, FL. 2000., p. 751] **PEER REVIEWED**

/LABORATORY ANIMALS: Subchronic or Prechronic Exposure/ Mice exposed to air containing 48,000 ppm for 3.5-4 hr daily up to cumulative total of 24 hr were in state of CNS depression, but survived, whereas they succumbed in coma when correspondingly exposed for 54 hr to air containing 54,000 ppm. [Clayton, G. D. and F. E. Clayton (eds.). Patty's Industrial Hygiene and Toxicology: Volume 2A, 2B, 2C: Toxicology. 3rd ed. New York: John Wiley Sons, 1981-1982., p. 4533] **PEER REVIEWED**

/LABORATORY ANIMALS: Subchronic or Prechronic Exposure/ In an oral study, Sprague-Dawley rats were dosed by oral gavage with 0, 100, 500, or 2500 mg/kg of methanol for 90 days. There were no differences between dosed animals and controls in body weight gain and food consumption. Brain weights were decreased in both sexes in the 2500 mg/kg dose group. Elevated serum glutamic pyruvate transaminase and alkaline phosphatase were noted in the 2500 mg/kg dose group, but there were no adverse treatment related effects in the gross pathology and histopathological evaluation. [Bingham, E.; Cohrssen, B.; Powell, C.H.; Patty's Toxicology 

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2/24/2011 htt p ://toxnet.nlm.nih. g ov/c g i- b in/sis/download.txtVolumes 1-9 5th ed. John Wiley & Sons. New York, N.Y. (2001)., p. V6 p.374] **PEER REVIEWED**

/LABORATORY ANIMALS: Subchronic or Prechronic Exposure/ Cynomolgus monkeys or Sprague-Dawley rats were exposed by inhalation to 0, 500, 2000, or 5000 ppm of methanol 6 hr/day, 5 day/week for 4 weeks. No treatment-related effects in the nasal turbinates, trachea, lungs, esophagus, liver, eye, or optic nerve were observed. Increased discharges around the eyes and nose were observed and were attributed to upper respiratory tract irritation. Groups of four male rats were exposed by inhalation to 0, 200, 2000, or 10,000 ppm of methanol 6 hr/day, 5 days/week for 1, 2, 4, or 6 weeks. Evaluation of a number of parameters including lung weights, surfactant levels, and enzyme activities did not reveal any adverse effects in the lung. No histopathological examinations were performed. [Bingham, E.; Cohrssen, B.; Powell, C.H.; Patty's Toxicology Volumes 1-9 5th ed. John Wiley & Sons. New York, N.Y. (2001)., p. V6 p.373] **PEER REVIEWED**

/LABORATORY ANIMALS: Subchronic or Prechronic Exposure/ Rats exposed to ...0.022 mg methanol/L of air 4 hr/day for 6 months and simultaneously administered 0.7 mg methanol/kg daily by gavage exhibited changes in blood morphology, oxidation-reduction processes and liver function. [WHO; Environ Health Criteria 196: Methanol p.79 (1997). Available from, as of July 18, 2005: http://www.inchem.org/documents/ehc/ehc/ehc196.htm] **PEER

REVIEWED**

/LABORATORY ANIMALS: Subchronic or Prechronic Exposure/ When ... repeated doses of 3 to 6 g/kg /were administered/ by gavage to rhesus monkeys (Macaca mulata) for 3-20 weeks, average serum levels of methanol of 4750 mg/L were attained within a few hours. Animals were killed at the end of treatment and livers examined histologically. Hepatocytes showed nucleolar segregation (zoning of nucleus), hyperplasia of endoplasmic reticulum and swelling of mitochondria. These changes were also found in one monkey sacrificed 12 weeks after the end of treatment. [WHO; Environ Health Criteria 196: Methanol p.93 (1997). Available from, as of July 18, 2005: http://www.inchem.org/documents/ehc/ehc/ehc196.htm] **PEER REVIEWED**

/LABORATORY ANIMALS: Chronic Exposure or Carcinogenicity/ It is unlikely that methanol is carcinogenic to mouse skin. In an experiment using four strains of female mice (Balb/c, Sencar, CD-1 and Swiss) to study N-nitrosomethylurea carcinogenesis, methanol was used as a solvent control. Four groups of 20 mice of each strain received 25 uL methanol twice weekly for 50 weeks followed by observation for lifespan. Only one skin tumor was observed among the 80 control animals. [WHO; Environ Health Criteria 196: Methanol p.74 (1997). Available from, as of July 14, 2005: http://www.inchem.org/documents/ehc/ehc/ehc196.htm] **PEER REVIEWED**

/LABORATORY ANIMALS: Chronic Exposure or Carcinogenicity/ Rats and mice were exposed to 0, 10, 100, or 1000 ppm of methanol 20 hr/day for 18 months (mice) or 24 months (rats). There was no evidence of carcinogenicity at 1000 ppm. Lung papillary adenomas and adrenal pheochromocytomas were observed and reported as "biologically insignificant." [Bingham, E.; Cohrssen, B.; Powell, C.H.; Patty's Toxicology Volumes 1-9 5th ed. John Wiley & Sons. New York, N.Y. (2001)., p. V6 p.378] **PEER REVIEWED**

/LABORATORY ANIMALS: Chronic Exposure or Carcinogenicity/ Groups of eight monkeys were exposed to 0, 10, 100, or 1000 ppm of methanol 22 hr/day for up to 2.5 years. Slight changes in the liver and kidney at 1000 ppm and some pathological changes in the nervous system of all animals at 1000 ppm were observed but were considered transient in nature and probably reversible. [Bingham, E.; Cohrssen, B.; Powell, C.H.; Patty's Toxicology Volumes 1-9 5th ed. John Wiley & Sons. New York, N.Y. (2001)., p. V6 p.378] **PEER REVIEWED**

/LABORATORY ANIMALS: Developmental or Reproductive Toxicity/ ...Developmental neurotoxicity of pregnant Long-Evans rats and their newborn offspring exposed to 5900 mg/cu m (4500 ppm) of methanol by inhalation for 6 hr daily /was studied/, beginning on gestation day 6, with both dams and pups then being exposed through postnatal day 21. Although findings suggested significant functional consequences in rats resulting from this exposure, these consequences were considered subtle in character. Exposure to 5900 mg methanol/cu m did not affect the suckling time and conditioned olfactory aversion test of newborn rats. Methanol exposed newborn pups were less active on postnatal day 18 and more active on postnatal day 25 than control newborn pups (motor activity test). The study found only isolated positive results that were small and variable. The two adult assays, the fixed-ratio wheel-running test and the stochastic discrimination test, yielded evidence of a significant methanol effect. No evidence of brain damage emerged on the basis of neuropathology, although differences in neural cell adhesion molecules (NCAMs) arising from methanol exposure were observed in neonatal cerebella. Methanol treatment caused a decrease in expression in both NCAM 140 and NCAM 180. [WHO; Environ Health Criteria 196: Methanol p.87 (1997). Available from, as of July 18, 2005: http://www.inchem.org/documents/ehc/ehc/ehc196.htm] **PEER REVIEWED**

/LABORATORY ANIMALS: Developmental or Reproductive Toxicity/ There have been conflicting reports on the effect of methanol on testicular hormones in rats. [Bingham, E.; Cohrssen, B.; Powell, C.H.; Patty's Toxicology Volumes 1-9 5th ed. John Wiley & Sons. New York, N.Y. (2001)., p. V6 

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2/24/2011 htt p ://toxnet.nlm.nih. g ov/c g i- b in/sis/download.txtp.378] **PEER REVIEWED**

/LABORATORY ANIMALS: Developmental or Reproductive Toxicity/ In Long-Evans rats dosed by oral gavage with 0, 0.8, or 1.6 g/kg of methanol for 21 days, serum testosterone levels were unaffected, but serum /lactate dehydrogenase/ was increased. Testis weights were decreased as were the number of morphologically normal caput and cauda epididymal sperm. [Bingham, E.; Cohrssen, B.; Powell, C.H.; Patty's Toxicology Volumes 1-9 5th ed. John Wiley & Sons. New York, N.Y. (2001)., p. V6 p.378] **PEER

REVIEWED**

/LABORATORY ANIMALS: Developmental or Reproductive Toxicity/ Transient neurological signs and reduced body weights were found in up to 20% of CD-1 dams exposed to 19,500 mg/cu m (15,000 ppm) methanol 6 hr/day throughout organogenesis (gestational days 6-15). Near-term fetuses revealed embryotoxicity (increased resorptions, reduced fetal weights and/or fetal malformations) at 13,000 and 19,500 mg/cu m (10,000 and 15,000 ppm) methanol while 3-day exposures at 6500 mg/cu m (5000 ppm) for 6 hr/day yielded no observable adverse effects. In the studies..., terata included neural and ocular defects, cleft palate, hydronephrosis, deformed tails and limb (paw and digit) anomalies. Neural tube defects and ocular lesions occurred after methanol inhalation by pregnant CD-1 mice between gestational days 7 and 9, while limb anomalies were induced only during gestational days 9-11; cleft palate and hydronephrosis were observed after exposure during either period. The spectrum of teratogenic effects depended upon both the stage of embryonic development and the number of methanol exposures. [WHO; Environ Health Criteria 196: Methanol p.85 (1997). Available from, as of July 14, 2005: http://www.inchem.org/documents/ehc/ehc/ehc196.htm] **PEER REVIEWED**

/LABORATORY ANIMALS: Developmental or Reproductive Toxicity/ Methanol was shown to impair uterine decidualization during early pregnancy in Holtzman rats administered 1.6, 2.4 or 3.2 g methanol/kg/day by gavage during days 1-8. Reductions in pregnant uterine and implantation site weights seen on day 9 were the result of methanol impedance of normal uterine decidualization as demonstrated by effects on decidual cell response technique. Methanol (3.2 g/kg/day) produced a non-specific maternal toxicity (reduction in body weight) by day 9, but no effect on days 11 or 20 on embryo and fetal survival or development were found. [WHO; Environ Health Criteria 196: Methanol p.86 (1997). Available from, as of July 18, 2005: http://www.inchem.org/documents/ehc/ehc/ehc196.htm] **PEER

REVIEWED**

/LABORATORY ANIMALS: Developmental or Reproductive Toxicity/ No effects on reproductive performance were reported in a two-generation reproductive study in F-344 rats administered 13, 130 or 1300 mg/cu m (10, 100 or 1000 ppm) methanol by inhalation for 18-20 hr/day. A statistically significant decrease in brain weight was found at the 1300 mg/cu m level in 3-, 6- and 8-week-old pups of the F1 generation. In the F2 generation reduced brain thymus and hypophysis weight was observed. [WHO; Environ Health Criteria 196: Methanol p.86 (1997). Available from, as of July 18, 2005: http://www.inchem.org/documents/ehc/ehc/ehc196.htm] **PEER REVIEWED**

/LABORATORY ANIMALS: Developmental or Reproductive Toxicity/ Depending on the concentration and duration of methanol exposure (0-20 mg/mL for 6 hr, 12 hr, or 1 or 4 days) on embryonic CD-1 mouse palate in serum-free organ culture, the medial epithelium either degenerated completely or remained intact in unfused palates (either condition would interfere with fusion). Cellular proliferation appeared to be a specific and sensitive target for methanol as craniofacial tissues responded to methanol with reduction in DNA content at an exposure that did not affect total protein. However both DNA and protein levels decreased with increasing exposure to methanol. Methanol selectively altered the morphological fate of the medial palatal epithelium cells and the specific effect on cell survival was exposure dependent. [WHO; Environ Health Criteria 196: Methanol p.89 (1997). Available from, as of July 18, 2005: http://www.inchem.org/documents/ehc/ehc/ehc196.htm] **PEER REVIEWED**

/LABORATORY ANIMALS: Developmental or Reproductive Toxicity/ Ethanol and methanol were compared with respect to their teratogenic activity on the brain /in C57BL mice/. /Mice were given doses of 1.7 or 2.45 g/kg bw by 2 ip injections 4 hours apart on gestational day 7 up to day 17./ ...1.7 g/kg methanol induced 30% resorptions and midfacial deficiencies and micro-anophthalmia in over 50% of live fetuses. 2.45 g/kg resulted in 55% resorptions and 100% of live fetuses having malformations of the holoprosencephaly spectrum (micro/anophthalmia, cebocephaly, absence of forebrain, premaxillary agenesis). [European Chemicals Bureau; IUCLID Dataset, Methanol (67-56-1) (2000 CD-ROM edition). Available from, as of July 19, 2005: http://ecb.jrc.ec.europa.eu/esis/] **PEER REVIEWED**

/LABORATORY ANIMALS: Developmental or Reproductive Toxicity/ The present study was designed to characterize maternal reproductive performance and early offspring effects following exposure to methanol (MeOH) vapor in a nonhuman primate model. The two-cohort study design used 48 adult female Macaca fascicularis (24/cohort) monkeys exposed to 0, 200, 600, or 1800 ppm MeOH vapor for approximately 2.5 hr/day, 7 days/week prior to breeding and throughout pregnancy. Maternal body weight measurement, clinical observations and health assessments were conducted routinely throughout the study. Menstrual cyclicity was monitored during the pre-breeding and breeding periods and timed matings were conducted with nonexposed males. Females were monitored closely during the last month of pregnancy. At 

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2/24/2011 htt p ://toxnet.nlm.nih. g ov/c g i- b in/sis/download.txtbirth, infant physical characteristics were measured and a newborn health assessment was conducted. Methanol exposure did not alter menstrual cycles, the number of breedings to conception or conception rate. A total of 34 live-born infants were delivered (control=8, 200 ppm=9, 600 ppm=8, 1800 ppm=9). One female each in the control and 600-ppm group delivered a stillborn infant and a cesarean section (C-section) was required to deliver a hydrocephalic infant who died in utero in the maternal 1800-ppm group. Although not statistically significant, five MeOH-exposed females were C-sectioned due to pregnancy complications such as uterine bleeding and prolonged unproductive labor. These complications were not observed in the control group. The mean length of pregnancy in the MeOH-exposed groups was significantly decreased by 6 to 8 days when compared to controls. There were no MeOH-related effects on offspring birthweight or newborn health status. The consistent reduction in length of pregnancy observed in the MeOH females may reflect a treatment effect on the fetal neuroendocrine system. Given that the fetal hypothalamic--pituitary-adrenal axis controls pregnancy length in most species, these results suggest a modest but significant effect of MeOH on the biochemical events that control the timing of birth. [Burbacher TM et al; Neurotoxicol Teratol 26 (5): 639-50 (2004)] **PEER REVIEWED** <a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15315813&query_hl=6" target=new>PubMed Abstract

/LABORATORY ANIMALS: Developmental or Reproductive Toxicity/ Methanol causes axial skeleton and craniofacial defects in both CD-1 and C57BL/6J mice during gastrulation, but C57BL/6J embryos are more severely affected. We evaluated methanol-induced pathogenesis in CD-1 and C57BL/6J embryos exposed during gastrulation in whole embryo culture. Conceptuses with 5-7 somites were exposed to 0, 1, 2, 3, 4, or 6 mg methanol/mL culture medium for 24 hr and embryonic morphology was assessed. Cell death was evaluated by histology and LysoTracker red staining, and cell-cycle distribution was evaluated by flow cytometry. In C57BL/6J embryos, craniofacial defects were observed at 3 mg methanol/mL and greater. The response for CD-1 embryos was different, with increased dysmorphology only at 6 mg/mL. However, protein content in CD-1 embryos was reduced at 3 mg methanol/mL and above, indicating growth retardation. Yolk sac toxicity occurred only at 6 mg methanol/mL in both strains. Methanol caused only small changes in cell-cycle distribution, while cell death was induced at 4 and 6 mg methanol/mL in both strains after 8 hr. The extent of cell death after 8 hr was greater in C57BL/6J embryos, and increased over time through 18 hr; in contrast, CD-1 embryos showed less cell death at 18 than at 8 hr, suggesting recovery. [Degitz SJ et al; Birth Defects Res A Clin Mol Teratol 70 (4): 179-84 (2004)] **PEER REVIEWED** <a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15108244&query_hl=14" target=new>PubMed Abstract

/LABORATORY ANIMALS: Developmental or Reproductive Toxicity/ Mouse embryos are more sensitive than rat embryos in response to methanol (CH(3)OH) and its ability to elicit developmental abnormalities. Intrinsic differences in the metabolism of CH(3)OH to formaldehyde (HCHO) and formic acid (HCOOH) by the enzymes alcohol dehydrogenase (ADH1), formaldehyde dehydrogenase (ADH3), and catalase may contribute to the observed species sensitivity. Specific activities for enzymes involved in CH(3)OH metabolism were determined in rat and mouse conceptuses during the organogenesis period of 8-25 somites. Spatial activity relationships were also compared separately in heads, hearts, trunks, and the visceral yolk sac (VYS) from early (7-12 somites) and late (20-22 somites) organogenesis-stage rat and mouse embryos. Catalase activities were similar between rat and mouse conceptuses. In the mouse heart, catalase activities were consistently lower when compared to other tissues. Specific activities for catalase were consistently highest in the VYS of both species when compared to other tissues of the embryo. These activities were highly significant in the 6-12 somite VYS. ADH1 activities were significantly higher in embryos when compared to VYS in both species, except for a 27% lower activity in the early 8-10 somite mouse embryo. Mouse ADH1 activities in the VYS were significantly lower throughout the organogenesis period when compared to the rat VYS or embryos of either species. Mouse activities were lower overall in specific tissues of the embryo but maintained the same relative proportions as in the rat. ADH3 activities in the rat VYS were significantly higher by 20% than those in the mouse. Mouse embryo ADH3 activities were slow to mature, starting at a level 42% below rat, and failed to reach optimal levels until the 14-16-somite stage. Heart ADH3 activities were also significantly lower in the mouse embryo at the 7-12-somite stage. Both species have lower ADH3 activities in the early heart, relative to other embryonic tissues. These results show a more slowly maturing capacity of the mouse embryo to remove HCHO, which provides a rationale for increased sensitivity of this species to CH(3)OH-induced embryotoxicity and teratogenicity. [Harris C et al; Reprod Toxicol 17 (3): 349-57 (2003)] **PEER REVIEWED** <a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=12759105&query_hl=22" target=new>PubMed Abstract

/LABORATORY ANIMALS: Developmental or Reproductive Toxicity/ The teratogenic effects of methanol were determined in rats. Pregnant Long-Evans-rats were gavaged on gestation day ten with a methanol dose of 0 to 5.2 mL/kg bw. The rats were pretreated with equal volumes of mineral-oil in order to prevent local gastric irritation. The rats were observed for signs of acute toxicity. Body weight was determined from gestation days zero to 20. On gestation day 20, the rats were sacrificed. Upon necropsy, both gross and microscopic histopathological changes were investigated. The fetuses were also examined for physical abnormalities. 

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2/24/2011 htt p ://toxnet.nlm.nih. g ov/c g i- b in/sis/download.txtCompared to the controls, food intake and body weight gain were significantly reduced in maternal rats treated with 5.2 mL/kg of methanol. No other indications of maternal toxicity were observed in any of the exposure groups. Among the groups, there were no significant differences in the number of postimplantation deaths or in the total loss per litter. Relative to controls, exposed male fetuses exhibited significantly decreased body weight. Among the exposed fetuses, undescended testes, eye defects, wavy thoracic cage, polycystic kidney, and missing appendages were noted. The number of total anomalies increased in a dose dependent manner following exposure to methanol. The number of eye defects and undescended testes each displayed a dose dependent relationship with methanol exposure. The methanol treated fetuses had a significantly increased frequency of hemorrhage in the nose and other areas, compared to controls. When corrected for body weight, the biparietal diameter of the fetal cranium was significantly increased in the methanol treated fetuses, compared to controls. [Youssef AF et al; Repro Toxicol 11 (4): 503-10 (1997)] **PEER REVIEWED**

/LABORATORY ANIMALS: Developmental or Reproductive Toxicity/ Mature male rats were examined for alterations in circulating free testosterone, luteinizing hormone and follicle stimulating hormone after inhalation of methanol vapor in a dynamic system for up to six weeks at doses ranging from 200 to 10,000 ppm. The most extensive effects were noticed after exposure to 200 ppm of methanol for 6 weeks, with serum testosterone concentration being 32% of the controls. A significant change in luteinizing hormone concentration after exposure to 10,000 ppm of methanol for six wk was also demonstrated while follicle stimulating and the elimination rate of testosterone from the blood (which indicates effects on the testicular synthesis of testosterone) remained unchanged throughout the experiments. [Cameron AM et al; Arch Toxicol 7: 441-3 (1984)] **PEER

REVIEWED**

/LABORATORY ANIMALS: Developmental or Reproductive Toxicity/ Methanol was administered via inhalation to groups of pregnant rats at 10000 ppm, 5000 ppm, or 0 ppm (control) for 7 hr/day on days 1 to 19 of gestation. Another group of rats was exposed similarly at 20000 ppm on days 7 to 15. The rats exposed at 20000 ppm exhibited slight maternal toxicity (a slightly unsteady gait), and a high incidence of congenital malformations (p < 0.001) (predominately extra or rudimentary cervical ribs), and urinary or

cardiovascular effects were observed in fetuses taken from rats sacrificed on day 20. Similar malformations were seen in the 10000 ppm group; however, the incidence was not significantly different from the controls. No adverse effects were noted in the 5000 ppm group [American Conference of Governmental Industrial Hygienists. Documentation of Threshold Limit Values for Chemical Substances and Physical Agents and Biological Exposure Indices for 2001. Cincinnati, OH. 2001., p. 2] **PEER REVIEWED**

/LABORATORY ANIMALS: Developmental or Reproductive Toxicity/ Methanol administered to C57BL/6J mice during gastrulation causes severe craniofacial dysmorphology. ...Dysmorphogenesis, cell death, cell cycle assessment, and effects on development of cranial ganglia and nerves observed following administration of methanol to pregnant C57BL/6J mice on gestation day (GD) 7 /are described/. Mice were injected (ip) on GD 7 with 0, 2.3, 3.4, or 4.9 g/kg methanol, split into two doses. In embryos of mice treated with 0 or 4.9 g/kg methanol, we used histology and LysoTracker red staining on GD 8 0 hr through GD 8 18 hr to examine cell death and dysmorphogenesis, and we also evaluated cell-cycle distribution and proliferation using flow cytometry (FCM) and /bromodeoxyuridine/ (BrdU) immunohistochemistry. On GD 10, ...the effect of GD 7 exposure to 0, 2.3, 3.4, or 4.9 g/kg methanol on cranial ganglia and nerve development using neurofilament immunohistochemistry /was evaluated/. Methanol treatment on GD 7 resulted in reduced mesenchyme surrounding the fore- and midbrain, and in the first branchial arches, by GD 8 12 hr. There were disruptions in the forebrain neuroepithelium and optic pit. Neural crest cell emigration from the mid- and hindbrain region was reduced in methanol-exposed embryos. Methanol had no apparent effect on BrdU incorporation or cell-cycle distribution on GD 8. Cell death was observed in the hindbrain region along the path of neural crest migration and in the trigeminal ganglion on GD 8 18 hr. Development of the cranial ganglia and nerves was adversely affected by methanol. Development of ganglia V, VIII, and IX was decreased at all dosage levels; ganglion VII was reduced at 3.4 and 4.9 g/kg, and ganglion X was reduced at 4.9 g/kg. [Degitz SJ et al; Birth Defects Res A Clin Mol Teratol 70 (4): 172-8 (2004)] **PEER

REVIEWED** <a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15108243" target=new>PubMed Abstract

/LABORATORY ANIMALS: Developmental or Reproductive Toxicity/ ...Pregnant C57BL/6J mice were administered two ip injections totaling 3.4 or 4.9 g/kg methanol or distilled water four hrs apart on gestation day 'GD' 7. On GD 17, litters were examined for numbers of live, dead and resorbed conceptuses, fetuses were weighed as a litter and examined externally, and all fetuses were double stained for skeletal analysis. No maternal intoxication was apparent, but the high dosage level caused a transient deficit in maternal weight gain. The number of live fetuses per litter was reduced at both dosages of methanol, and fetal weight was lower in the high dosage group. Craniofacial defects were observed in 55.8% of fetuses in the low dosage group and 91.0% of fetuses in the high dosage group, including micro/anophthalmia, holoprosencephaly, facial clefts and gross facial angenesis. Skeletal malformations, particularly of the cervical vertebrae, were observed at both dosages of methanol, and were similar to 

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2/24/2011 htt p ://toxnet.nlm.nih. g ov/c g i- b in/sis/download.txtthose previously reported in the CD-1 mouse following methanol exposure. [Rogers JM et al; Birth Defects Res B Dev Reprod Toxicol 71 (2): 80-8 (2004)] **PEER REVIEWED** <a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15098201&query_hl=18" target=new>PubMed Abstract

/LABORATORY ANIMALS: Developmental or Reproductive Toxicity/ Female Sprague-Dawley rats were exposed by inhalation to 0, 5000, and 10,000 ppm for 7 hr/day during gestational days 1 to 19 and to 20,000 ppm 7 hr/day during gestational days 7 to 15. At 20,000 ppm, methanol produced slight maternal toxicity (unsteady gait only). Fetal body weights were decreased in the 10,000- and 20,000-ppm groups with a high incidence of malformations. The malformations were predominantly extra or rudimentary cervical ribs and urinary or cardiovascular defects. Similar malformations were observed at 10,000 ppm, but the incidence was not statistically significant from controls. No maternal or developmental effects were noted at 5,000 ppm. The blood methanol concentrations in female rates at the end of the first 7 hr of exposure were 100 mg/mL at 5,000 ppm, 2240 mg/mL at 10,000 ppm, and 8650 mg/mL at 20,000 ppm. [Bingham, E.; Cohrssen, B.; Powell, C.H.; Patty's Toxicology Volumes 1-9 5th ed. John Wiley & Sons. New York, N.Y. (2001)., p. V6 p.376] **PEER REVIEWED**

/LABORATORY ANIMALS: Developmental or Reproductive Toxicity/ Female CD-1 mice were exposed by inhalation to 0, 2000, 5000, and 15,000, ppm of methanol 7 hr/day during gestational days 6 to 15. A food-deprived nonexposed group was added. Methanol exposure did not produce maternal toxicity, but all exposure groups gained less weight than fed or food-deprived controls. Most of the litters of dams exposed to 15,000 ppm were completely resorbed and 38% of fetuses that survived to day 17 had exencephaly. Exposure to 5000 ppm resulted in exencephaly in about one-third of the litters and in 5 to 10% of the fetuses. At 2000 ppm, 1 of 220 fetuses had exencephaly, and there was none in the controls. The maternal plasma methanol level in exposed pregnant female CD-1 mice was 2000 and 8000 mg/mL after the first 7 hr of exposure at 5000 and 15,000 ppm, respectively. [Bingham, E.; Cohrssen, B.; Powell, C.H.; Patty's Toxicology Volumes 1-9 5th ed. John Wiley & Sons. New York, N.Y. (2001)., p. V6 p.376] **PEER REVIEWED**

/LABORATORY ANIMALS: Developmental or Reproductive Toxicity/ A spectrum of cephalic neural tube defects was found in near-term (gestation day 17) CD-1 mouse fetuses following maternal inhalation of methanol at high concentration (19,500 mg/cu m; 15,000 ppm) for 6 hr/day during neurulation (gestation days 7-9). Dysraphism, chiefly exencephaly, occurred in 15% of the fetuses, usually in association with reduction or absence of multiple bones in the craniofacial skeleton and ocular anomalies (prematurely open eyelids, cataracts, retinal folds). Exposure to a high concentration of methanol (19,500 mg/cu m) injured the multiple stem populations in the neuralating mouse embryo. Significant neural pathology may remain in older conceptuses even in the absence of gross lesions. [WHO; Environ Health Criteria 196: Methanol p.85 (1997). Available from, as of July 18, 2005: http://www.inchem.org/documents/ehc/ehc/ehc196.htm] **PEER REVIEWED**

/LABORATORY ANIMALS: Developmental or Reproductive Toxicity/ In a single oral exposure, pregnant female Long-Evans rats were dosed by gavage with 0,1.3, 2.6, and 5.2 mL/kg of methanol on gestational day 10. At 5.2 mL/kg, maternal weight loss was > 10%. A significant decrease in fetal body weight (11 to 21%) was noted. Both internal and external examination of the fetuses showed a dose-related increase in total anomalies of 0.6, 4.8, 6.7, and 17.3% at doses of 0, 1.3, 2.6, and 5.2 mL/kg of methanol respectively. Those dose-related anomalies involved undescended testes and the eye. [Bingham, E.; Cohrssen, B.; Powell, C.H.; Patty's Toxicology Volumes 1-9 5th ed. John Wiley & Sons. New York, N.Y. (2001)., p. V6 p.377] **PEER REVIEWED**

/LABORATORY ANIMALS: Developmental or Reproductive Toxicity/ In whole-rat embryo culture, day 9 embryos were explanted and cultured in 0, 4000, 6000, 8000, 12,000, or 16,000 mg of methanol/mL serum for 24 hr and then

transferred to rat serum alone for 24 hr. Methanol concentrations of 8000 mg/mL and higher resulted in a dose-related decrease in somite number and overall development. The 12,000-mg/mL concentration resulted in embryo lethality, as well as dysmorphogenesis, and 16,00 mg/mL was embryolethal. Head length and crown-rump length were not affected by methanol exposure below embryolethal concentrations. [Bingham, E.; Cohrssen, B.; Powell, C.H.; Patty's Toxicology Volumes 1-9 5th ed. John Wiley & Sons. New York, N.Y. (2001)., p. V6 p.377] **PEER REVIEWED**

/LABORATORY ANIMALS: Developmental or Reproductive Toxicity/ Pregnant Long-Evans rats were exposed to 2% methanol in drinking water on gestational days 15 to 17 or 17 to 19. The animals were allowed to deliver, and the postnatal behavior of the pups was assessed. Methanol consumption averaged 2.5 g/kg/day. Methanol had no effect on maternal weight gain, gestational duration, water consumption, litter size, birth weight, neonatal mortality, postnatal growth, or the time until eye opening. However, compared to nonexposed rats, prenatal exposure impaired suckling behavior, as well as homing behavior, as determined by increased time to return to the nest area. No significant behavioral effects were noted in the offspring of female rats exposed to 15,000 ppm of methanol for 7 hr/day during gestational days 7 to 19. Maternal blood methanol levels, measured from samples taken within 15 minutes after removal from the exposure chamber, declined from about 3800 ug/mL to 3100 ug/mL on the 12th day of exposure. [Bingham, E.; Cohrssen, B.; Powell, C.H.; Patty's 

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2/24/2011 htt p ://toxnet.nlm.nih. g ov/c g i- b in/sis/download.txtToxicology Volumes 1-9 5th ed. John Wiley & Sons. New York, N.Y. (2001)., p. V6 p.377] **PEER REVIEWED**

/LABORATORY ANIMALS: Neurotoxicity/ Rats exposed to 1.0, 2.0 and 3.0 g methanol/kg by gavage exhibited an altered response in an operant conditioning paradigm designed to assess motor deficits produced by neurotoxicants. Methanol decreased the rate of response in a dose-related fashion that suggested impaired coordination and/or reduced endurance. [WHO; Environ Health Criteria 196: Methanol p.74 (1997). Available from, as of July 14, 2005: http://www.inchem.org/documents/ehc/ehc/ehc196.htm]

**PEER REVIEWED**

/LABORATORY ANIMALS: Neurotoxicity/ In contrast to many studies of methanol toxicity that reported no effect of low doses, two Russian studies reported evidence of neurobehavioral toxicity at low doses as shown by altered chronaximetry (chronaximetry is the ratio of the minimum time necessary for a stimulus of twice the absolute threshold intensity to evoke a response measured as muscle contractions in response to an electric current applied to an animal's hind leg). Normally, the flexor chronaxia is shorter than the extensor chronaxia, and their ratio is stated to be relatively stable. /One study/... reported that the average chronaxia ratio for rats exposed in the high-dose group (49.77 mg/cu m) for 12 hr/day, 5 days/wk for 3 months, differed significantly from that in the control group of animals at week 8 of exposure. The average chronaxia ratio returned to normal during the recovery period and the effects in the low-dose group (1.77 mg/cu m) were insignificant. Histopathological changes found in the high-dose group, but not in the low-dose group, included poorly defined changes in the mucous membranes of the trachea and bronchi, hyperplasia of the submucosa of the trachea, slight lymphoid infiltration, swelling and hypertrophy of the muscle layer of arteries, slight degenerative changes to the liver and changes in the neurons of the cerebral cortex. /The second study/... reported that male rats exposed continuously for 90 days to a concentration of 5.3 mg/cu m (4 ppm) of methanol vapor, exhibited changes in chronaxia ratio between antagonistic muscles, in whole blood cholinesterase activity, in urinary excretion of coproporphyrin and in albumin-globulin ratio of the serum. Male rats exposed to 0.57 mg/cu m (0.4 ppm) of methanol vapor continuously for 90 days showed no changes. It should be noted, however, that an analysis of these studies... indicated that, due to flaws in the study designs, these studies do not provide adequate evidence of an association between neurobehavioral effects and low-level exposure to methanol. Both studies were limited by the use of small numbers of animals per dose group, as well as insufficient reporting of experimental methods, study results and statistical analysis. /It was/... also stated that the biological significance of changes in the chronaxia ratio is uncertain. [WHO; Environ Health Criteria 196: Methanol p.74 (1997). Available from, as of July 14, 2005: http://www.inchem.org/documents/ehc/ehc/ehc196.htm] **PEER

REVIEWED**

/LABORATORY ANIMALS: Neurotoxicity/ ...In the presence of 4% methanol, approximately 35% of embryos die and methanol exposure leads to severe CNS defects in about half those embryos, where the longitudinal connectives are dorsally displaced and commissure formation is severely reduced. In addition, a range of morphological defects in other germ layers is seen, and cell movement is adversely affected by methanol exposure. Although we did not find any evidence to suggest that methanol exposure affects the capacity of neuroblasts to divide or induces inappropriate apoptosis in these cells, in the CNS of germ band retracted embryos, the number of apoptotic nuclei is significantly increased in methanol-exposed embryos in comparison to controls, particularly in and adjacent to the ventral midline. Apoptosis contributes significantly to methanol neurotoxicity because embryos lacking the cell death genes grim, hid, and reaper have milder CNS defects resulting from methanol exposure than wild-type embryos. Our data suggest that when neurons and glia are severely adversely affected by methanol exposure, the damaged cells are cleared by apoptosis, leading to embryonic death. [Mellerick DM, Liu H; J Neurobiol 60 (3): 308-13 (2004)] **PEER REVIEWED** <a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15281069&query_hl=8" target=new>PubMed Abstract

/LABORATORY ANIMALS: Neurotoxicity/ ...In the present work, a chronic methanol intoxication scheme (2 g/kg/day ip for 2 weeks) was carried out in Sprague-Dawley rats previously depleted of folates with methotrexate. Taurine (2%) in drinking water was also administered in two groups of

animals. Blood formate levels were increased in methotrexate-methanol-treated animals with respect to controls (0.98 +/- 0.09 and 0.30 +/- 0.03 mM, respectively). Amino acids and monoamines were determined in plasma and in retina, optic nerve, hippocampus, and posterior cortex by HPLC with fluorescence or electrochemical detection. The main finding was an increased aspartate content in the optic nerve in methotrexate methanol-treated animals. Methanol alone increased glutamate, aspartate, glutamine, taurine, 5-hydroxytryptamine, and 5-hydroxyindoleacetic acid levels in the hippocampus and 5-hydroxytryptamine in the retina. Taurine administration had no significant effect on changes induced by methanol treatment. ...Chronic methanol administration produced accumulation of aspartate, an excitotoxic amino acid, in the optic nerve. [Gonzalez-Quevedo A et al; Toxicol Appl Pharmacol 185 (2): 77-84 (2002)] **PEER REVIEWED** <a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=12490131" target=new>PubMed Abstract 

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2/24/2011 htt p ://toxnet.nlm.nih. g ov/c g i- b in/sis/download.txt/LABORATORY ANIMALS: Neurotoxicity/ Role of folic acid on methanol-induced neurotoxicity was studied in pups at Postnatal Day (PND) 45 exposed to methanol (1%, 2% and 4%, v/v) during lactation through mothers maintained on folic acid-deficient (FD) and folic acid-sufficient (FS) diet. A gradual loss in the body weight gain was observed in the pups exposed to 2% and 4% methanol in the FD group, while FS group exhibited this alteration only at 4% exposure. The assessment of spontaneous locomotor activity (SLA) showing a significant increase in the distance travelled was observed in the 2% and 4% methanol-exposed groups in both the FS and FD animals when compared with their respective controls, but the effect was more marked in the FD group. A significant decrease in the conditioned avoidance response (CAR) was observed in pups exposed to 2% and 4% methanol in the FD group at PND 45. The results also suggest that disturbances in dopaminergic and cholinergic receptors were more pronounced in the FD group as compared to the FS group. A significant decrease in striatal dopamine levels was also observed in the FD group at 2% and 4% methanol exposure, while in the FS group, a significant decrease was exhibited only at 4% methanol exposure. An aberrant increase in the expression of Growth-Associated Protein (GAP-43), a neuron-specific growth-associated protein was observed in pups in the FD group exposed to 2% and 4% methanol, while an increase in the expression of GAP-43 in the FS group was found only at 4% methanol exposure in the hippocampal region as compared to their respective controls. [Aziz MH et al; Neurotoxicol and Teratol 24 (4): 519-27 (2002)] **PEER REVIEWED**

/LABORATORY ANIMALS: Neurotoxicity/ Behavioral effects induced by perinatal methanol vapor exposure were studied in neonatal and adult rats. Pregnant Long-Evans-hooded-rats were exposed to 0 or 4,500 ppm methanol vapor 6 hr/day starting on gestational day six in 2 cubic meter hexagonal Rochester chambers. At delivery, the litters culled to four offspring of each sex, were kept in the exposure chambers with the dams up to weaning, postnatal day (PND) 21. The offspring were evaluated as neonates for their ability to find a dam's nipple in the suckling test administered on PND5 and olfactory aversion using orange-oil and methyl-salicylate as odorants on PND10. Motor activity was evaluated on PND18 and PND25. The offspring were evaluated as adults by measuring their performance in two operant conditioning paradigms: running a specific number of revolutions in a rotating field for a feed pellet reward (running wheel test) and performing a complex lever pressing task for a feed pellet reward (stochastic spatial discrimination learning (SSDL) test). Methanol exposure did not affect performance in the suckling or odor aversion test. The exposed rats showed lower levels of motor activity on PND18, but higher levels of activity on PND25. When tested as adults, methanol exposed male rats showed decreases in the rate of running in the running wheel test compared to their baseline performance. Exposed females showed increased rates of running. Methanol exposed rats of both sexes showed impaired performance on the SSDL test at asymptotic levels of performance. /It was concluded/... that exposure to 4,500ppm methanol vapor during early development produces subtle changes in behavior in both neonatal and adult rats. [Stern S et al; Fundam and Appl Toxicol 36 (2): 163-76 (1997)]

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/GENOTOXICITY/ In mice exposed by inhalation to 800 or 4000 ppm of methanol for 5 days, there were no increased frequencies of micronuclei in blood cells; sister chromatid exchanges, chromosomal aberrations, or micronuclei in lung cells; or synaptosomal complex damage in spermatocytes. The frequency of micronucleated erythrocytes in normal or folate-deficient mice treated with four daily intraperitoneal injections of up to 2500 mg/kg of methanol was not increased. No increase in micronuclei was observed in the bone marrow of mice exposed to methanol. [Bingham, E.; Cohrssen, B.; Powell, C.H.; Patty's Toxicology Volumes 1-9 5th ed. John Wiley & Sons. New York, N.Y. (2001)., p. V6 p.379] **PEER

REVIEWED**

/GENOTOXICITY/ 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. [Bingham, E.; Cohrssen, B.; Powell, C.H.; Patty's Toxicology Volumes 1-9 5th ed. John Wiley & Sons. New York, N.Y. (2001)., p. V6 p.379] **PEER

REVIEWED**

/GENOTOXICITY/ 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. [Bingham, E.; Cohrssen, B.; Powell, C.H.; Patty's Toxicology Volumes 1-9 5th ed. John Wiley & Sons. New York, N.Y. (2001)., p. V6 p.379] **PEER REVIEWED**

/GENOTOXICITY/ Methanol was negative for gene mutation at the ade 6 locus in the yeast Schizosaccharomyces pombe with or without the postmitochondrial fraction from mouse liver. It was also negative in a mutagenicity test for n+1 aneuploidy arising from meiotic disfunction of linkage group I in the fungus Neurospora crassa. [WHO; Environ Health Criteria 196: Methanol p.90 (1997). Available from, as of July 18, 2005: http://www.inchem.org/documents/ehc/ehc/ehc196.htm] **PEER REVIEWED**

/GENOTOXICITY/ Urine from mice administered five daily doses of methanol 

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2/24/2011 htt p ://toxnet.nlm.nih. g ov/c g i- b in/sis/download.txt(5 g/kg total) showed no mutagenic activity, and no increase in the incidence of abnormal sperm was reported. Oral administration of 1 g methanol/kg to mice increased the incidence of chromosomal aberrations, particularly aneuploidy and SCEs, as well as the incidence of micronuclei in polychromatic erythrocytes. [WHO; Environ Health Criteria 196: Methanol p.91 (1997). Available from, as of July 18, 2005: http://www.inchem.org/documents/ehc/ehc/ehc196.htm] **PEER REVIEWED**

/GENOTOXICITY/ A negative consensus resulted from all sister chromatid exchange tests when no exogenous metabolic activation system was used. [Latt SA et al; Mutation Res (1) 87: 17-62 (1981)] **PEER REVIEWED**

/GENOTOXICITY/ A negative consensus resulted from both cell transformation in primary cells using limited lifetime strains and cell transformation via viral enhancement tests when no exogenous metabolic activation system was used. [Heidelberger C et al; Mutation Res (3) 114: 283-385 (1983)]

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/GENOTOXICITY/ A negative consensus resulted from all Neurospora crassa tests when no exogenous metabolic activation system was used. [Brockman HE et al; Mutation Res (2) 133: 87-134 (1984)] **PEER REVIEWED**

/ALTERNATIVE IN VITRO TESTS/ Crude methanol extracts of red and white wines were added to diethyl ether in order to divide them into the anthocyanin fraction (insoluble in diethyl ether) and fractions containing other flavonoids and their derivatives (soluble in diethyl ether). However, the white wine did not contain anthocyanins (all of the methanol extract was soluble in diethyl ether). When HCT-15 cells, derived from human colon cancer or AGS cells, derived from human gastric cancer, were cultured with these fractions, the anthocyanin fraction from the red wine and the non-anthocyanic substances extracted from red and white wines suppressed the growth of the cells, and the suppression rate by the anthocyanin fraction was significantly higher than that of the other fractions. Thin-layer chromatographic analysis revealed mostly delphinidin in the anthocyanin fraction. The other fractions contained mostly flavonoids and their derivatives. The sugars in all fractions were mainly glucose, fucose, and fructose. Flow cytometric study suggested that the anthocyanin fraction blocked mostly S, G2, and M phase, and the non-anthocyanic flavonoids also blocked these phases, although the histographic pattern varied depending on the fractions. Methanol insoluble but water soluble fractions (mostly free sugars) of red and white wines did not show such suppressive effects. [Kamei H et al; Cancer Biother Radiopharm 13 (6): 447-52 (1998)] **PEER REVIEWED** <a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=10851437&query_hl=40" target=new>PubMed Abstract

/ALTERNATIVE IN VITRO TESTS/ Methanol was tested for cytotoxicity (inhibition of cell growth in cultures of Ascites Sarcoma BP8 cells) as a screening system for acute toxicity in humans. The IC50 value (growth inhibition for 50%) was 673 mM. [European Chemicals Bureau; IUCLID Dataset, Methanol (67-56-1) (2000 CD-ROM edition). Available from, as of July 19, 2005: http://ecb.jrc.ec.europa.eu/esis/] **PEER REVIEWED**

/ALTERNATIVE IN VITRO TESTS/ ...The potential of administered methanol to incorporate into and/or alter the methylation of embryonal DNA or to affect specific protein methylation /was investigated/. Gestational day 8 CD-1 mouse embryos were grown for 24 hr in culture medium (CM) with 0, 4, or 8 mg MeOH + 20 uCi 14C-MeOH/mL. At the end of the culture period, yolk sacs and embryos were separated for each treatment group. The DNA was purified by cesium chloride gradient centrifugation in the presence of ethidium bromide and 14C incorporation was determined. Methylation of a selected gene, Hoxc-8, was assessed by using methylation-specific restriction enzymes. The 14C activity was found superimposed over the DNA-containing fraction, indicating incorporation. DNA from embryos treated with 4 mg MeOH/mL CM gave the highest incorporation of 14C-MeOH (8 mg/mL was growth inhibiting). Methylation of Hoxc-8 appeared to be increased in embryos treated with 4 mg MeOH/mL CM, but not in embryos treated with 8 mg MeOH/mL. Lack of incorporation of methylation at the higher concentration may be due to the failure of embryos to grow at this concentration of MeOH. The incorporation of 14C-MeOH into embryo proteins was investigated by polyacrylamide gel electrophoresis (PAGE) and autoradiography. Incorporation of 14C-MeOH into specific proteins was observed but the labeling specificity was not methanol dose-related. These results indicate that methyl groups from 14C-MeOH are incorporated into mouse embryo DNA and protein. [Huang YS et al; Repro Toxicol 15 (4): 429-35 (2001)] **PEER REVIEWED**

/OTHER TOXICITY INFORMATION/ Several factors may contribute to the unique vulnerability of the retina and optic nerve to the cytotoxic actions of formate. One component of this selectivity is related to the differences in the distribution of formate in the eye and the brain. Formate

concentrations measured in the vitreous humor and retinas of methanol-intoxicated rats were equivalent to or greater than corresponding blood formate concentrations. In contrast, the concentrations of formate in the brain were significantly lower than blood formate concentrations. These data suggest that the toxic actions of methanol on the visual system may be due to the selective accumulation of formate in the vitreous humor and the retina as compared with other regions of the CNS. Secondly, the retina has a very limited metabolic capacity to oxidize and thus detoxify formate. Thirdly, cytochrome oxidase activity and ATP concentrations have been shown to be selectively reduced in the retina, optic nerve and brain 

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2/24/2011 htt p ://toxnet.nlm.nih. g ov/c g i- b in/sis/download.txtin methanol-intoxicated rats, suggesting that there may be tissue- and cell-specific differences in mitochondrial populations and in the actions of formate on mitochondrial function. Finally, in vitro studies in

isolated retinal and cardiac mitochondria have shown that formate selectively inhibits retinal mitochondrial ATP synthesis. These findings support the hypothesis that formate acts as a selective mitochondrial

toxin in the retina and establish a link between the effects of formate in vitro and the retinal toxicity associated with formate accumulation in methanol intoxication. [WHO; Environ Health Criteria 196: Methanol p.99 (1997). Available from, as of July 18, 2005: http://www.inchem.org/documents/ehc/ehc/ehc196.htm] **PEER REVIEWED**

ECOTOXICITY EXCERPTS: /AQUATIC SPECIES/ At 40,000-80,000 mg/L, methanol killed Chironomus dorsalis meig larvae within 2 days; 500-20,000 mg/L within 26 days. 50-200 mg/L delayed imago emergence; at emergence, limb defects or hemorrhages were observed. 250 mg/L cause morphological changes in larval development. [Puzikova NB; Tr Sarat Otd Gosniorkh 13: 151-3 (1975)] **PEER REVIEWED**

/AQUATIC SPECIES/ Cyprinus carpio /(Common carp) were exposed to methanol for up to/ 72 hr. ...Methanol treatment did not affect serum glucose but led to increased serum cortisol, decreased serum protein, decreased serum cholesterol, decreased liver glycogen, and increased muscle glycogen. /The effective concentration was/ > /=790 mg/L. [European Chemicals Bureau; IUCLID Dataset, Methanol (67-56-1) (2000 CD-ROM edition). Available from, as of July 15, 2005: http://ecb.jrc.ec.europa.eu/esis/]

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/AQUATIC SPECIES/ ...The mussel, Mytilus edulis, /was exposed/ to methanol concentrations of 1, 2, 3, 5 and 10% (v/v) for 96 hr. All the mussels in both the 5 and 10% exposure groups died within 13.5 hr. Sublethal narcotic effects such as slow movement and sporadic filter feeding were reported in mussels exposed to 2 and 3%. Mussels exposed to 1% methanol exhibited no adverse effects during the 96-hr exposure period. [WHO; Environ Health Criteria 196: Methanol p.115 (1997). Available from, as of July 19, 2005: http://www.inchem.org/documents/ehc/ehc/ehc196.htm] **PEER REVIEWED**

/AQUATIC SPECIES/ ...The effect of methanol on the embryonic development of the medaka fish (Oryzias latipes) /was determined/. The eggs were exposed to methanol in both Petri dishes and vials. No effects on embryonic development were reported at a methanol concentration of 0.5%. [WHO; Environ Health Criteria 196: Methanol p.123 (1997). Available from, as of July 19, 2005: http://www.inchem.org/documents/ehc/ehc/ehc196.htm]

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/AQUATIC SPECIES/ The effect of methanol on the fertilization of chum salmon (Oncorhynchus keta) ova was examined at methanol exposure levels of 0.001% to 10% by volume (7.9 to 79 000 mg/lL). Both gametes (sperm and unfertilized ova) and fertilized eggs were exposed to methanol for brief periods. Exposures up to and including 1% methanol did not significantly affect fertilization, survival to hatching, hatching time, alevin size at hatch or physical deformities among alevins, although a methanol concentration of 10% was lethal in most cases. [WHO; Environ Health Criteria 196: Methanol p.123 (1997). Available from, as of July 19, 2005: http://www.inchem.org/documents/ehc/ehc/ehc196.htm] **PEER REVIEWED**

/AQUATIC SPECIES/ Static renewal bioassays were conducted in the laboratory and in outdoor artificial enclosures to evaluate toxic effects of methanol to one teleost fish and two aquatic invertebrates and to limnological variables of aquatic ecosystem. Ninety-six-hour acute toxicity tests revealed cladoceran crustacea Moina micrura as the most sensitive to methanol (LC50, 4.82 g/L), followed by freshwater teleost Oreochromis mossambicus (LC50, 15.32 g/L) and oligochaete worm Branchiura sowerbyi (LC50, 54.89 g/L). The fish, when exposed to lethal concentrations of methanol, showed difficulties in respiration and swimming. The oligochaete body wrinkled and fragmented under lethal exposure of methanol. Effects of five sublethal concentrations of methanol (0, 23.75, 47.49, 736.10, and 1527.60 mg/L) on the feeding rate of the fish and on its growth and reproduction were evaluated by separate bioassays. Ninety-six-hour bioassays in the laboratory showed significant reduction in the appetite of fish when exposed to 736.10 mg/L or higher concentrations of methanol. Chronic toxicity bioassays (90 days) in outdoor enclosures showed a reduction in growth, maturity index and fecundity of fish at 47.49 mg/L or higher concentrations of methanol. Primary productivity, phytoplankton population, and alkalinity of water were also reduced at these concentrations. Chronic exposure to 1527.60 mg/L methanol resulted in damages of the epithelium of primary and secondary gill lamellae of the fish. The results revealed 23.75 mg/L as the no-observed-effect concentration (NOEC) of methanol to freshwater aquatic ecosystem. [Kaviraj A et al; Int J Toxicol 23 (1): 55-63 (2004)]

**PEER REVIEWED** <a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15162848&query_hl=12" target=new>PubMed Abstract

/AQUATIC SPECIES/ ...The dehydrated /Artemia salina (Brine shrimp)/ cysts were directly exposed for 48 hr to the action of three alcohols, methanol, ethanol, and n-propanol. No teratogenic or lethal effects on larvae were found at any methanol or ethanol concentrations. Predicted values of effect concentration, EC1, EC10 and EC50 were calculated from the estimated probit models for larva growth inhibition, GI, and for cyst lethal concentration, LC. At concentrations of 0.21 M methanol and 0.13 M 

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2/24/2011 htt p ://toxnet.nlm.nih. g ov/c g i- b in/sis/download.txtethanol, there were no signs of alterations in Artemia salina cyst development; these concentrations show a NOEC (No Observed Effect Concentration) value, and properly employed do not interfere with effects due to a given chemical. [Vismara C; Chemosphere 37 (14-15): 3027-3034 (1998)] **PEER REVIEWED**

NON-HUMAN TOXICITY VALUES: LD50 Rat oral 5628 mg/kg [Lewis, R.J. Sax's Dangerous Properties of Industrial Materials. 9th ed. Volumes 1-3. New York, NY: Van Nostrand Reinhold, 1996., p. 2174] **PEER REVIEWED**

LC50 Rat inhalation 64000 ppm/4 hr [Lewis, R.J. Sax's Dangerous Properties of Industrial Materials. 9th ed. Volumes 1-3. New York, NY: Van Nostrand Reinhold, 1996., p. 2174] **PEER REVIEWED**

LC50 Rat inhalation 87.5 mg/L/6 hr [European Chemicals Bureau; IUCLID Dataset, Methanol (67-56-1) (2000 CD-ROM edition). Available from, as of July 19, 2005: http://ecb.jrc.ec.europa.eu/esis/] **PEER REVIEWED**

LD50 Rat ip 7529 mg/kg [Lewis, R.J. Sax's Dangerous Properties of Industrial Materials. 9th ed. Volumes 1-3. New York, NY: Van Nostrand Reinhold, 1996., p. 2174] **PEER REVIEWED**

LD50 Rat iv 2131 mg/kg [Lewis, R.J. Sax's Dangerous Properties of Industrial Materials. 9th ed. Volumes 1-3. New York, NY: Van Nostrand Reinhold, 1996., p. 2174] **PEER REVIEWED**

LD50 Mouse oral 7300 mg/kg [Lewis, R.J. Sax's Dangerous Properties of Industrial Materials. 9th ed. Volumes 1-3. New York, NY: Van Nostrand Reinhold, 1996., p. 2174] **PEER REVIEWED**

LD50 Mouse ip 10765 mg/kg [Lewis, R.J. Sax's Dangerous Properties of Industrial Materials. 9th ed. Volumes 1-3. New York, NY: Van Nostrand Reinhold, 1996., p. 2174] **PEER REVIEWED**

LD50 Mouse sc 4100 mg/kg bw [European Chemicals Bureau; IUCLID Dataset, Methanol (67-56-1) (2000 CD-ROM edition). Available from, as of July 19, 2005: http://ecb.jrc.ec.europa.eu/esis/] **PEER REVIEWED**

LD50 Mouse iv 4710 mg/kg [Lewis, R.J. Sax's Dangerous Properties of Industrial Materials. 9th ed. Volumes 1-3. New York, NY: Van Nostrand Reinhold, 1996., p. 2174] **PEER REVIEWED**

LD50 Rabbit oral 14.4 g/kg [Bingham, E.; Cohrssen, B.; Powell, C.H.; Patty's Toxicology Volumes 1-9 5th ed. John Wiley & Sons. New York, N.Y. (2001)., p. V6 p.372] **PEER REVIEWED**

LD50 Rabbit dermal 15,800 mg/kg bw [European Chemicals Bureau; IUCLID Dataset, Methanol (67-56-1) (2000 CD-ROM edition). Available from, as of July 19, 2005: http://ecb.jrc.ec.europa.eu/esis/] **PEER REVIEWED**

LD50 Rabbit ip 1826 mg/kg bw [European Chemicals Bureau; IUCLID Dataset, Methanol (67-56-1) (2000 CD-ROM edition). Available from, as of July 19, 2005: http://ecb.jrc.ec.europa.eu/esis/] **PEER REVIEWED**

LD50 Rabbit iv 8907 mg/kg bw [European Chemicals Bureau; IUCLID Dataset, Methanol (67-56-1) (2000 CD-ROM edition). Available from, as of July 19, 2005: http://ecb.jrc.ec.europa.eu/esis/] **PEER REVIEWED**

LD50 Monkey oral 2-3 g/kg [Bingham, E.; Cohrssen, B.; Powell, C.H.; Patty's Toxicology Volumes 1-9 5th ed. John Wiley & Sons. New York, N.Y. (2001)., p. V6 p.372] **PEER REVIEWED**

LD50 Macaca nemestrina (Pigtail monkey) ip 3-4 g/kg [WHO; Environ Health Criteria 196: Methanol p.78 (1997). Available from, as of July 18, 2005: http://www.inchem.org/documents/ehc/ehc/ehc196.htm] **PEER REVIEWED**

LD50 Dog oral 8000 mg/kg bw [European Chemicals Bureau; IUCLID Dataset, Methanol (67-56-1) (2000 CD-ROM edition). Available from, as of July 19, 2005: http://ecb.jrc.ec.europa.eu/esis/] **PEER REVIEWED**

LC50 Cat inhalation 85.41 mg/L/4.5 hr [European Chemicals Bureau; IUCLID Dataset, Methanol (67-56-1) (2000 CD-ROM edition). Available from, as of July 19, 2005: http://ecb.jrc.ec.europa.eu/esis/] **PEER REVIEWED**

LC50 Cat inhalation 43.68 mg/L/6 hr [European Chemicals Bureau; IUCLID Dataset, Methanol (67-56-1) (2000 CD-ROM edition). Available from, as of July 19, 2005: http://ecb.jrc.ec.europa.eu/esis/] **PEER REVIEWED**

LD50 Guinea pig ip 3556 mg/kg bw [European Chemicals Bureau; IUCLID Dataset, Methanol (67-56-1) (2000 CD-ROM edition). Available from, as of July 19, 2005: http://ecb.jrc.ec.europa.eu/esis/] **PEER REVIEWED**

LD50 Hamster ip 8555 mg/kg bw [European Chemicals Bureau; IUCLID Dataset, Methanol (67-56-1) (2000 CD-ROM edition). Available from, as of July 19, 2005: http://ecb.jrc.ec.europa.eu/esis/] **PEER REVIEWED**

ECOTOXICITY VALUES: LC50 Pimephales promelas (fathead minnows) 29.4 g/L/96 hr, (28-29 days old), confidence limit= 28.5-30.4; Test conditions: Water temp= 25 deg C, dissolved oxygen= 7.3 mg/L, water hardness= 43.5 mg/l calcium carbonate, 

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2/24/2011 htt p ://toxnet.nlm.nih. g ov/c g i- b in/sis/download.txtalkalinity= 46.6 calcium carbonate, tank volume= 6.3 L, additions= 5.71 V/D, pH= 7.66 (0.03). [Brooke, L.T., D.J. Call, D.T. Geiger and C.E. Northcott (eds.). Acute Toxicities of Organic Chemicals to Fathead Minnows (Pimephales Promelas). Superior, WI: Center for Lake Superior Environmental Studies Univ. of Wisconsin Superior, 1984., p. 19] **PEER

REVIEWED**

LC50 Pimephales promelas (Fathead minnow, 28-32 day old, 0.126 g) 29,700 mg/L/24 hr; flow-through, 23.3+/-1.7 deg C, hardness 46.4 mg/L CaCO3, pH 7.0-8.0 /from table/ [WHO; Environ Health Criteria 196: Methanol p.119 (1997). Available from, as of July 19, 2005: http://www.inchem.org/documents/ehc/ehc/ehc196.htm] **PEER REVIEWED**

LC50 Pimephales promelas (Fathead minnow, 30 day old 0.12 g) 28,100 mg/L/96 hr; flow-through, 24-26 deg C, hardness 45.5 mg/L CaCO3, pH 7.5 /from table/ [WHO; Environ Health Criteria 196: Methanol p.120 (1997). Available from, as of July 19, 2005: http://www.inchem.org/documents/ehc/ehc/ehc196.htm] **PEER REVIEWED**

LC50 Artemia salina (Brine shrimp, 24 hr old) 1578.84 mg/L/24 hr; static, 25 deg C, seawater /from table/ [WHO; Environ Health Criteria 196: Methanol p.117 (1997). Available from, as of July 19, 2005: http://www.inchem.org/documents/ehc/ehc/ehc196.htm] **PEER REVIEWED**

LC50 Artemia salina (Brine shrimp, 48 hr old) 1101.46 mg/L/24 hr; static, 25 deg C, seawater /from table/ [WHO; Environ Health Criteria 196: Methanol p.117 (1997). Available from, as of July 19, 2005: http://www.inchem.org/documents/ehc/ehc/ehc196.htm] **PEER REVIEWED**

LC50 Artemia salina (Brine shrimp, 72 hr old) 900.73 mg/L/24 hr; static, 25 deg C, seawater /from table/ [WHO; Environ Health Criteria 196: Methanol p.117 (1997). Available from, as of July 19, 2005: http://www.inchem.org/documents/ehc/ehc/ehc196.htm] **PEER REVIEWED**

LC50 Oncorhynchus mykiss (Rainbow trout, 0.8 g) 19,000 mg/L/96 hr; static, 12 deg C, hardness 44 mg/L CaCO3, pH 7.4 /from table/ [WHO; Environ Health Criteria 196: Methanol p.119 (1997). Available from, as of July 19, 2005: http://www.inchem.org/documents/ehc/ehc/ehc196.htm] **PEER REVIEWED**

LC50 Oncorhynchus mykiss (Rainbow trout, juvenile 0.813 g) 20,300 mg/L/24 hr; flow-through, 12.7+/-1 deg C, hardness 46.4 mg/L CaCO3, pH 7.0-8.0 /from table/ [WHO; Environ Health Criteria 196: Methanol p.119 (1997). Available from, as of July 19, 2005: http://www.inchem.org/documents/ehc/ehc/ehc196.htm] **PEER REVIEWED**

LC50 Oncorhynchus mykiss (Rainbow trout, juvenile 0.813 g) 20,100 mg/L/96 hr; flow-through, 12.7+/-1 deg C, hardness 46.4 mg/L CaCO3, pH 7.0-8.0 /from table/ [WHO; Environ Health Criteria 196: Methanol p.119 (1997). Available from, as of July 19, 2005: http://www.inchem.org/documents/ehc/ehc/ehc196.htm] **PEER REVIEWED**

LC50 Lepomis macrochirus (Bluegill) 15,400 mg/L/96 hr; flow-through [European Chemicals Bureau; IUCLID Dataset, Methanol (67-56-1) (2000 CD-ROM edition). Available from, as of July 15, 2005: http://ecb.jrc.ec.europa.eu/esis/] **PEER REVIEWED**

LC50 Lepomis macrochirus (Bluegill) 19,230 mg/L/24 hr; flow-through [European Chemicals Bureau; IUCLID Dataset, Methanol (67-56-1) (2000 CD-ROM edition). Available from, as of July 15, 2005: http://ecb.jrc.ec.europa.eu/esis/] **PEER REVIEWED**

LC50 Lepomis macrochirus (Bluegill sunfish, juvenile 3.07 g) 19,100 mg/L/24 hr; flow-through, 19.8+/-2.3 deg C, hardness 46.4 mg/L CaCO3, pH 7.0-8.0 /from table/ [WHO; Environ Health Criteria 196: Methanol p.120 (1997). Available from, as of July 19, 2005: http://www.inchem.org/documents/ehc/ehc/ehc196.htm] **PEER REVIEWED**

LC50 Lepomis macrochirus (Bluegill sunfish, juvenile 3.07 g) 15,400 mg/L/96 hr; flow-through, 19.8+/-2.3 deg C, hardness 46.4 mg/L CaCO3, pH 7.0-8.0 /from table/ [WHO; Environ Health Criteria 196: Methanol p.120 (1997). Available from, as of July 19, 2005: http://www.inchem.org/documents/ehc/ehc/ehc196.htm] **PEER REVIEWED**

LC50 Nitocra spinipes (Harpacticoid copepod, adult) 12,000 mg/L/96 hr; static, 21+/-1 deg C, pH 7.9 /from table/ [WHO; Environ Health Criteria 196: Methanol p.118 (1997). Available from, as of July 19, 2005: http://www.inchem.org/documents/ehc/ehc/ehc196.htm] **PEER REVIEWED**

LC50 Poecilia reticulata (Guppy) 11.5 mg/L/14 days; semistatic [European Chemicals Bureau; IUCLID Dataset, Methanol (67-56-1) (2000 CD-ROM edition). Available from, as of July 15, 2005: http://ecb.jrc.ec.europa.eu/esis/] **PEER REVIEWED**

LC50 Poecilia reticulata (Guppy, 2-3 months) 10,860 mg/L/7 days; semistatic (test solutions renewed every 24 hours), 21-23 deg C, hardness 25 mg/L CaCO3 /from table/ [WHO; Environ Health Criteria 196: Methanol p.121 (1997). Available from, as of July 19, 2005: http://www.inchem.org/documents/ehc/ehc/ehc196.htm] **PEER REVIEWED**

LC50 Alburnus alburnus (Bleak, 8 cm) 28,000 mg/L/96 hr; static, 10 deg C, pH 7.9 /from table/ [WHO; Environ Health Criteria 196: Methanol p.121 

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2/24/2011 htt p ://toxnet.nlm.nih. g ov/c g i- b in/sis/download.txt(1997). Available from, as of July 19, 2005: http://www.inchem.org/documents/ehc/ehc/ehc196.htm] **PEER REVIEWED**

LC50 Leuciscus idus melanotus (Golden orfe) > 10,000 mg/L/48 hr; static [European Chemicals Bureau; IUCLID Dataset, Methanol (67-56-1) (2000 CD-ROM edition). Available from, as of July 15, 2005: http://ecb.jrc.ec.europa.eu/esis/] **PEER REVIEWED**

EC50 Daphnia magna (Water flea; immobilizaiton) > 10,000 mg/L/24 hr; static, 20 deg C, total hardness 2.5 mmol/L CaCO3, pH 7.8-8.2 /from table/ [WHO; Environ Health Criteria 196: Methanol p.116 (1997). Available from, as of July 19, 2005: http://www.inchem.org/documents/ehc/ehc/ehc196.htm]

**PEER REVIEWED**

LC50 Gammarus fasciatus > 100 mg/L/96 hr /Conditions of bioassay not specified in source examined/ [European Chemicals Bureau; IUCLID Dataset, Methanol (67-56-1) (2000 CD-ROM edition). Available from, as of July 15, 2005: http://ecb.jrc.ec.europa.eu/esis/] **PEER REVIEWED**

LC50 Helisoma trivolvis (aquatic mollusk) > 100 mg/L/96 hr /Conditions of bioassay not specified in source examined/ [European Chemicals Bureau; IUCLID Dataset, Methanol (67-56-1) (2000 CD-ROM edition). Available from, as of July 15, 2005: http://ecb.jrc.ec.europa.eu/esis/] **PEER REVIEWED**

LC50 Dugesia tigrina (aquatic worm) > 100 mg/L/96 hr /Conditions of bioassay not specified in source examined/ [European Chemicals Bureau; IUCLID Dataset, Methanol (67-56-1) (2000 CD-ROM edition). Available from, as of July 15, 2005: http://ecb.jrc.ec.europa.eu/esis/] **PEER REVIEWED**

LC50 Ceriodaphnia dubia 11 mg/L/48 hr /Conditions of bioassay not specified in source examined/ [European Chemicals Bureau; IUCLID Dataset, Methanol (67-56-1) (2000 CD-ROM edition). Available from, as of July 15, 2005: http://ecb.jrc.ec.europa.eu/esis/] **PEER REVIEWED**

LC50 Lumbriculus variegatus (aquatic worm) > 100 mg/L/96 hr /Conditions of bioassay not specified in source examined/ [European Chemicals Bureau; IUCLID Dataset, Methanol (67-56-1) (2000 CD-ROM edition). Available from, as of July 15, 2005: http://ecb.jrc.ec.europa.eu/esis/] **PEER REVIEWED**

EC50 Photobacterium posphoreum (marine bacterium; inhibition of luminescence) 14,700 mg/L/15 min /Conditions of bioassay not specified in source examined/ [WHO; Environ Health Criteria 196: Methanol p.114 (1997). Available from, as of July 19, 2005: http://www.inchem.org/documents/ehc/ehc/ehc196.htm] **PEER REVIEWED**

LC50 Photobacterium posphoreum (marine bacterium) 7690 mg/L/4 hr /Conditions of bioassay not specified in source examined/ [WHO; Environ Health Criteria 196: Methanol p.114 (1997). Available from, as of July 19, 2005: http://www.inchem.org/documents/ehc/ehc/ehc196.htm] **PEER

REVIEWED**

LC50 Paramecium caudatum (Ciliate protozoan) 44,860 mg/L/10 min /Conditions of bioassay not specified in source examined/ [WHO; Environ Health Criteria 196: Methanol p.114 (1997). Available from, as of July 19, 2005: http://www.inchem.org/documents/ehc/ehc/ehc196.htm] **PEER

REVIEWED**

LC50 Daphnia pulex (Water flea, < 24 hr old) 19,500 mg/L/18 hr; static, 22 deg C, hardness 23+/-2 mg/L CaCO3 /from table/ [WHO; Environ Health Criteria 196: Methanol p.116 (1997). Available from, as of July 19, 2005: http://www.inchem.org/documents/ehc/ehc/ehc196.htm] **PEER REVIEWED**

EC50 Daphnia obtusa (Water flea, < 24 hr old; immobilization) 23,500 mg/L/24 hr; static, 20+/-2 deg C, hardness 250 mg/L CaCO3, pH 7.8+/-0.2 /from table/ [WHO; Environ Health Criteria 196: Methanol p.116 (1997). Available from, as of July 19, 2005: http://www.inchem.org/documents/ehc/ehc/ehc196.htm] **PEER REVIEWED**

EC50 Daphnia obtusa (Water flea, < 24 hr old; immobilization) 22,200 mg/L/48 hr; static, 20+/-2 deg C, hardness 250 mg/L CaCO3, pH 7.8+/-0.2 /from table/ [WHO; Environ Health Criteria 196: Methanol p.116 (1997). Available from, as of July 19, 2005: http://www.inchem.org/documents/ehc/ehc/ehc196.htm] **PEER REVIEWED**

LC50 Crangon crangon (Brown shrimp, adult) 1975 mg/L/48 hr; static, 15 deg C, seawater /from table/ [WHO; Environ Health Criteria 196: Methanol p.117 (1997). Available from, as of July 19, 2005: http://www.inchem.org/documents/ehc/ehc/ehc196.htm] **PEER REVIEWED**

LC50 Crangon crangon (Brown shrimp, adult) 1340 mg/L/96 hr; semistatic (test solutions renewed every 24 hr), 15 deg C, seawater /from table/ [WHO; Environ Health Criteria 196: Methanol p.117 (1997). Available from, as of July 19, 2005: http://www.inchem.org/documents/ehc/ehc/ehc196.htm]

**PEER REVIEWED**

LC50 Crangon crangon (Brown shrimp, adult) 10,000 mg/L/24 hr; static, 24.5 deg C, seawater /from table/ [WHO; Environ Health Criteria 196: Methanol p.117 (1997). Available from, as of July 19, 2005: http://www.inchem.org/documents/ehc/ehc/ehc196.htm] **PEER REVIEWED**

LC50 Mytilus edulis (Mussel, 5-7 cm) 15,900 mg/L/96 hr; flow-through, 

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2/24/2011 htt p ://toxnet.nlm.nih. g ov/c g i- b in/sis/download.txt15+/-0.5 deg C, seawater /from table/ [WHO; Environ Health Criteria 196: Methanol p.118 (1997). Available from, as of July 19, 2005: http://www.inchem.org/documents/ehc/ehc/ehc196.htm] **PEER REVIEWED**

LC50 Palaemonetes kadiakensis (Glass shrimp, juvenile) 21,900 mg/L/18 hr; static, 23+/-2 deg C /from table/ [WHO; Environ Health Criteria 196: Methanol p.117 (1997). Available from, as of July 19, 2005: http://www.inchem.org/documents/ehc/ehc/ehc196.htm] **PEER REVIEWED**

LC50 Cardium edule (Cockle, adult) 7900 mg/L/48 hr; static, 15 deg C, seawater /from table/ [WHO; Environ Health Criteria 196: Methanol p.118 (1997). Available from, as of July 19, 2005: http://www.inchem.org/documents/ehc/ehc/ehc196.htm] **PEER REVIEWED**

LC50 Hyallela azteca (Scud, juvenile) 19,350 mg/L/18 hr; static, 23+/-2 deg C /from table/ [WHO; Environ Health Criteria 196: Methanol p.118 (1997). Available from, as of July 19, 2005: http://www.inchem.org/documents/ehc/ehc/ehc196.htm] **PEER REVIEWED**

LC50 Agonus cataphractus (Armed bullhead, adult) 7900-26,070 mg/L/96 hr; semistatic (test solutions renewed every 24 hours), 15 deg C, seawater /from table/ [WHO; Environ Health Criteria 196: Methanol p.122 (1997). Available from, as of July 19, 2005: http://www.inchem.org/documents/ehc/ehc/ehc196.htm] **PEER REVIEWED**

EC50 Tetrahymena pyriformis (Protozoa; population growth inhibition test) 18756.34 mg/L/48 hr /Conditions of bioassay not specified in source examined/ /95% pure/ [European Chemicals Bureau; IUCLID Dataset, Methanol (67-56-1) (2000 CD-ROM edition). Available from, as of July 19, 2005: http://ecb.jrc.ec.europa.eu/esis/] **PEER REVIEWED**

LC50 Anodonta imbecilis (Mussel) 37.02 mg/L/48 hr; static [Keller AE; Bull Environ Contam Toxicol 51 (5): 696-702 (1993). ECOTOX database on Methanol (67-56-1). Available from, as of July 20, 2005: http://cfpub.epa.gov/ecotox/quick_query.htm] **PEER REVIEWED**

LC50 Oryzias latipes (Medaka) > 10,000 mg/L/24 hr; static /formulated product/ [Tsuji S et al; Eisei Kagaku 32 (1): 46-53 (1986). ECOTOX database on Methanol (67-56-1). Available from, as of July 20, 2005: http://cfpub.epa.gov/ecotox/quick_query.htm] **PEER REVIEWED**

METABOLISM/PHARMACOKINETICS:

METABOLISM/METABOLITES: Methanol (labeled with (14)C) is slowly metabolized by rat and in 2 days is excreted as carbon dioxide (65% of dose), and unchanged methanol (14%) in expired air, and as formate (3%) and methanol (3%) in urine. [Parke, D. V. The Biochemistry of Foreign Compounds. Oxford: Pergamon Press, 1968., p. 212] **PEER REVIEWED**

...Methanol is... metabolized by pathways of 1-carbon metabolism, giving rise to methyl group of choline, etc. In the rabbit it may also result in... a small amount of methylglucuronide. [Parke, D. V. The Biochemistry of Foreign Compounds. Oxford: Pergamon Press, 1968., p. 213] **PEER

REVIEWED**

Oxidation of methanol appears to occur by coupled peroxidative reactions catalyzed by hepatic catalase, and in rats occurs at a much slower rate (25 mg/kg/hr) than oxidation of ethanol (175 mg/kg/hr). [Parke, D. V. The Biochemistry of Foreign Compounds. Oxford: Pergamon Press, 1968., p. 213]

**PEER REVIEWED**

... Methanol is metabolized in human beings by the same enzymes that metabolize ethanol, alcohol dehydrogenase and aldehyde dehydrogenase, to toxic intermediates, formaldehyde and formic acid. Oxidation of methanol, like that of ethanol, proceeds at a rate that is independent of its concentration in the blood. However, the rate is only one-seventh that of the oxidation of ethanol, and complete oxidation and excretion of methanol thus usually require several days. [Hardman, J.G., L.E. Limbird, P.B., A.G. Gilman. Goodman and Gilman's The Pharmacological Basis of Therapeutics. 10th ed. New York, NY: McGraw-Hill, 2001., p. 1886] **PEER

REVIEWED**

Several primary alcohols... yield moderate amounts of monosulfate esters. This pathway has been detected for methanol... in rats. [Testa, B. and P. Jenner. Drug Metabolism: Chemical & Biochemical Aspects. New York: Marcel Dekker, Inc., 1976., p. 188] **PEER REVIEWED**

The first step in the metabolism of methanol is oxidation to formaldehyde. In rats, a catalase-peroxidase system is primarily responsible for the initial step, whereas in humans and monkeys, alcohol dehydrogenase plays a major role. Despite the difference, the initial metabolic step proceeds at similar rates. The third possible pathway in methanol oxidation is hepatic microsomal oxidation involving the cytochrome P450 system. [Bingham, E.; Cohrssen, B.; Powell, C.H.; Patty's Toxicology Volumes 1-9 5th ed. John Wiley & Sons. New York, N.Y. (2001)., p. V6 p.374] **PEER REVIEWED**

Following a 2 mg/kg oral dose of methanol to primates and rats, about 90% is metabolized. Even after a high dose of 1 g/kg of radiolabeled methanol 

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2/24/2011 htt p ://toxnet.nlm.nih. g ov/c g i- b in/sis/download.txtto monkeys, 78% of the activity was recovered within 24 hr as exhaled CO2. [Bingham, E.; Cohrssen, B.; Powell, C.H.; Patty's Toxicology Volumes 1-9 5th ed. John Wiley & Sons. New York, N.Y. (2001)., p. V6 p.375] **PEER

REVIEWED**

In the liver, alcohol dehydrogenase (ADH) metabolizes approximately 75-85% of methanol to formaldehyde, which is then oxidized by aldehyde dehydrogenase to formic acid. In the presence of folate, formic acid is converted to carbon dioxide and water. This beneficial aspect of folate has been demonstrated both in mice and in nonhuman primates. Folate-deficient rats were more susceptible to methanol toxicity than were folate-rich rats. Monkeys treated with folate after methanol administration were relatively resistant to methanol toxicity, and when methanol toxicity was allowed to develop, it was reversed after folate

treatment. ...At low concentrations methanol metabolism follows zero-order kinetics at a rate of 8.5 mg/dL/hr. At much higher methanol concentrations first-order kinetics occur, possibly because of increased pulmonary elimination. In the presence of therapeutic levels of ethanol, the half-life ranges from 30-52 hours with a median of 43 hours. In the presence of fomepizole, the mean half-life is 54 hours. [Goldfrank, L.R. (ed). Goldfrank's Toxicologic Emergencies. 7th Edition McGraw-Hill New York, New York 2002., p. 982] **PEER REVIEWED**

Methanol is ... released during the metabolism of food additives such as the artificial sweetener, aspartame, and /dimethyl dicarbonate/ (DMDC), a yeast inhibitor added to a variety of beverages. [DHHS/NTP; NTP-CERHR Expert Panel Report on the Reproductive and Developmental Toxicity of Methanol p.7 (April 2002) NTP-CERHR-MeOH-02. Available from, as of July 20, 2005: http://cerhr.niehs.nih.gov/news/methanol/methanol_final.pdf]

**PEER REVIEWED**

The disposition of methanol and its putative toxic metabolite formate has been studied in humans, non-human primates, and rodents after exposure to high, neurotoxic doses. The rate at which rodents detoxify formate is more rapid than that of primates. Formate, an endogenous biological substrate, is detoxified by metabolism to /carbon dioxide/ via a tetrahydrofolate-(THF) dependent pathway. Species with high hepatic THF levels, such as rodents, are less sensitive to the neurotoxic effects of large methanol doses compared with species with low THF levels, such as primates. Data on the capacity of primates to detoxify formate derived from inhalation of low levels of methanol are critical for assessing human risk from methanol fuels. Female cynomolgus monkeys exposed to low concentrations of [14C]methanol (10-200 ppm) for 2 hr have blood levels of methanol-derived formate that are 100-to 1000-fold lower than endogenous levels of formate. Healthy human volunteers exposed at rest or during exercise to 200 ppm methanol for 6 hr or exposed to 20 mg/kg orally have elevated blood levels of methanol, but blood formate concentrations are not significantly increased above endogenous concentrations. Deficiencies in THF may prolong blood levels of formate and increase the likelihood of toxic effects. Limited studies in non-human primates with low THF levels exposed to 900 ppm methanol for 2 hr have shown that concentrations of methanol-derived formate in blood remain below endogenous levels. [Medinsky MA, Dorman DC; Toxicology Letters 82-83: 707-11 (1995)] **PEER

REVIEWED**

Wistar male rats were exposed to methanol and toluene vapors by inhalation individually and simultaneously. Blood was sampled from the tail of the rats at 0, 1.5 and 3 hr after a 6-hr exposure and the methanol and/or toluene concentrations were measured by the headspace-gas chromatography-mass spectrometry (GC). Major metabolites of methanol and toluene, that is, formic acid and hippuric acid in urine were measured at 0, 18 and 42 hr after the end of the exposure. The toluene concentration in blood in the simultaneous exposure group was lower than that in the toluene exposure one. The biological half time of toluene in blood in the simultaneous exposure group was shorter than that in the single exposure one. The excretion rate of hippuric acid in urine in the simultaneous exposure group was significantly lower than that in the toluene exposure one when both the methanol and toluene concentrations were 300 ppm. These results suggest that the metabolic rate of toluene was enhanced by methanol. On the other hand, the biological half time of methanol in blood and the formic acid concentration in urine were not significantly different in the single and simultaneous exposure groups, although the methanol concentration in blood in the simultaneous exposure group was lower than that in the methanol exposure one. [Hori H et al; J of Occup Health 41 (3): 149-153 (1999)] **PEER REVIEWED**

ABSORPTION, DISTRIBUTION & EXCRETION: 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. [Bingham, E.; Cohrssen, B.; Powell, C.H.; Patty's Toxicology Volumes 1-9 5th ed. John Wiley & Sons. New York, N.Y. (2001)., p. V6 p.374] **PEER REVIEWED**

Methyl alcohol is readily absorbed from GI and respiratory tracts. [Gosselin, R.E., R.P. Smith, H.C. Hodge. Clinical Toxicology of Commercial Products. 5th ed. Baltimore: Williams and Wilkins, 1984., p. III-275]

**PEER REVIEWED**

The rate of absorption /of methanol from the gastrointestinal tract is 

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2/24/2011 htt p ://toxnet.nlm.nih. g ov/c g i- b in/sis/download.txtapproximately/... 8.4 mg/sq cm/hr. Time to peak serum concentration... after ingestion /is/... 30-60 minutes for methanol... . [Goldfrank, L.R. (ed). Goldfrank's Toxicologic Emergencies. 7th Edition McGraw-Hill New York, New York 2002., p. 982] **PEER REVIEWED**

Distribution of methyl alcohol within tissues of dogs exposed to 4000 and 15000 ppm in air over periods ranging from 12 hr to 5 days was found to be rapid. ... Highest concentrations were found in blood, eye fluid, bile, urine, and lowest in bone marrow and fatty tissue. ... 1-7 mg of methyl alcohol/g of blood (100-700 mg/100 mL) was found ... in blood of rats following oral administration of 4 g of methyl Alcohol/kg of body weight. [Clayton, G. D. and F. E. Clayton (eds.). Patty's Industrial Hygiene and Toxicology: Volume 2A, 2B, 2C: Toxicology. 3rd ed. New York: John Wiley Sons, 1981-1982., p. 4534] **PEER REVIEWED**

... 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. ... [Clayton, G. D. and F. E. Clayton (eds.). Patty's Industrial Hygiene and Toxicology: Volume 2A, 2B, 2C: Toxicology. 3rd ed. New York: John Wiley Sons, 1981-1982., p. 4537] **PEER REVIEWED**

70% of methyl alcohol lost by animals was eliminated in expired air. [Clayton, G. D. and F. E. Clayton (eds.). Patty's Industrial Hygiene and Toxicology: Volume 2A, 2B, 2C: Toxicology. 3rd ed. New York: John Wiley Sons, 1981-1982., p. 4535] **PEER REVIEWED**

Two human male volunteers were exposed on several different occasions to methyl alcohol vapor at concentrations of from 650 to 1,430 mg/cu m (approximately 500-1,100 ppm). Concentrations were verified by analyzing air samples collected at frequent intervals during and after exposures for methyl alcohol content. Using urinary methyl alcohol concentrations as an index of methyl alcohol absorption, it was concluded that the rate of absorption was proportional to the concentration of the vapor inhaled. Exposure to methyl alcohol vapor at a concentration of 1,430 mg/cu m (approximately 1,100 ppm) for 2 1/2 hr resulted in a urinary methyl alcohol concentration of 2.56 mg/100 mL. Exposure periods were not sufficiently long to determine whether the rate of excretion would increase to equal the rate of absorption. An exposure period of 3-4 hr was all that could be reasonably tolerated. The threshold of intoxication was calculated for these two workers as 2,800 ppm (3,670 mg/cu m) and 3,000 ppm (3,930 mg/cu m) respectively. [Leaf G, Zatman LJ; Br J Ind Med 9: 19-31 (1952) as cited in NIOSH; Criteria Document: Methyl Alcohol p.39-40 (1976) DHEW Pub. NIOSH 76-148] **PEER REVIEWED**

Pulmonary retention in humans after 8 hr of inhalation exposure to methanol was 58% of the inhaled amount, regardless of the exposure level, duration of the exposure, or pulmonary ventilation. The methanol blood concentrations in dogs exposed repeatedly to vapor concentrations of 450 or 500 ppm, 8 hr/day, for 379 continuous days varied between 10 and 15 mg/100mL at the end of an 8 hr period, but occasional values as high as 52 mg/dL were obtained. [Bingham, E.; Cohrssen, B.; Powell, C.H.; Patty's Toxicology Volumes 1-9 5th ed. John Wiley & Sons. New York, N.Y. (2001)., p. V6 p.374] **PEER REVIEWED**

Rabbits given a single oral dose of methanol (2 to 10 g/kg) excreted 0.1

to 1.1% of it as formate and 13 to 20% of it as methanol in the urine within 47 to 143 hr. [Bingham, E.; Cohrssen, B.; Powell, C.H.; Patty's Toxicology Volumes 1-9 5th ed. John Wiley & Sons. New York, N.Y. (2001)., p. V6 p.375] **PEER REVIEWED**

Following a 2 mL/kg oral dose of methanol to rabbits, 5.3% was excreted in the expired air and 7.8% in the urine. [Bingham, E.; Cohrssen, B.; Powell, C.H.; Patty's Toxicology Volumes 1-9 5th ed. John Wiley & Sons. New York, N.Y. (2001)., p. V6 p.375] **PEER REVIEWED**

Dogs given 1 to 2 g/kg of methanol orally excreted 5 to 15% in the urine as formate and 5 to 8% as unchanged methanol. Dogs excrete more formate than rabbits after ingestion of methanol. [Bingham, E.; Cohrssen, B.; Powell, C.H.; Patty's Toxicology Volumes 1-9 5th ed. John Wiley & Sons. New York, N.Y. (2001)., p. V6 p.375] **PEER REVIEWED**

The rate of elimination for methanol from the blood is much lower than that of ethanol. The rate of methanol disappearance from the blood also depends on dose. Elimination follows first order kinetics. The rat and the monkey have similar capabilities for eliminating methanol at low inhalation exposures (200 ppm) but not at higher exposure levels. [Bingham, E.; Cohrssen, B.; Powell, C.H.; Patty's Toxicology Volumes 1-9 5th ed. John Wiley & Sons. New York, N.Y. (2001)., p. V6 p.375] **PEER

REVIEWED**

In rats exposed by inhalation to 200, 1200, and 2000 ppm methanol for 6 hr, the peak methanol concentrations in the blood were 3.3, 32.2, and 90.8 mg/mL, respectively, indicating a nonlinear response. [Bingham, E.; Cohrssen, B.; Powell, C.H.; Patty's Toxicology Volumes 1-9 5th ed. John Wiley & Sons. New York, N.Y. (2001)., p. V6 p.375] **PEER REVIEWED**

In Rhesus monkeys exposed to 200, 1200, and 2000 ppm of methanol for 6 hr, the peak methanol concentration in the blood was 7.7, 39.3 and 66.1 mg/mL, 

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2/24/2011 htt p ://toxnet.nlm.nih. g ov/c g i- b in/sis/download.txtrespectively, a directly proportional response. ... Exposures did not

cause an elevation in blood formate levels that could be attributed to methanol metabolism. [Bingham, E.; Cohrssen, B.; Powell, C.H.; Patty's Toxicology Volumes 1-9 5th ed. John Wiley & Sons. New York, N.Y. (2001)., p. V6 p.375] **PEER REVIEWED**

Female Long-Evans rats were exposed by inhalation to 4500 ppm of methanol 6 hr/day from gestational day 6 to birth, and dams and their pups were exposed until postnatal day 21. The average methanol concentrations were 0.35, 0.499, and 1.3 mg/mL for pregnant dams, nursing dams, and neonates, respectively. In pregnant female Long-Evans rats exposed to 2% methanol in drinking water on gestational day 17 and euthanized the next day (approximately 2 g/kg consumed), there was a rapid equilibration of methanol across placental and blood-brain barriers. [Bingham, E.; Cohrssen, B.; Powell, C.H.; Patty's Toxicology Volumes 1-9 5th ed. John Wiley & Sons. New York, N.Y. (2001)., p. V6 p.375] **PEER REVIEWED**

Low-level inhalation exposures to methanol cause small increases in blood and urine formate levels. A study was conducted of 20 workers in a printing office who were exposed to an estimated methanol concentration between 111 and 174 mg/cu m throughout the work day. During the day, the blood level of formate increased an average of 4.7 mg/L (3.2 mg/L before the work shift to 7.9 mg/L when work ended), and urinary formate increased an average of 7.1 mg/L. A control group maintained relatively stable levels throughout the day of 5.3 mg/L of blood and 11.8 mg/L of urine. [Bingham, E.; Cohrssen, B.; Powell, C.H.; Patty's Toxicology Volumes 1-9 5th ed. John Wiley & Sons. New York, N.Y. (2001)., p. V6 p.381] **PEER

REVIEWED**

... Twenty workers were exposed throughout the day to 120 mg/cu m of methanol. At the end of the day, blood and urine levels of methanol were 8.9 and 21.8 mg/L, respectively; a control group had a mean blood and urine level of < 0.6 and 1.1 mg/L, respectively. Urinary formic acid was significantly higher in the workers (29.9 mg/L) than in the controls (12.7 mg/L). [Bingham, E.; Cohrssen, B.; Powell, C.H.; Patty's Toxicology Volumes 1-9 5th ed. John Wiley & Sons. New York, N.Y. (2001)., p. V6 p.381] **PEER REVIEWED**

In an inhalation study, six human volunteers were exposed to 200 ppm methanol for 6 hr. At the end of the exposure, the blood methanol level was increased from a mean of 1.8 mg/mL to 7.0 mg/mL. With light exercise, the total amount of methanol inhaled during the exposure period was 1.8 times higher than inhaled at rest; however, no statistically significant

increase in blood methanol was observed. Formate did not accumulate in the blood above the background level in subjects at rest or during excercise. [Bingham, E.; Cohrssen, B.; Powell, C.H.; Patty's Toxicology Volumes 1-9 5th ed. John Wiley & Sons. New York, N.Y. (2001)., p. V6 p.381] **PEER

REVIEWED**

The dermal uptake rate of liquid methanol applied to the forearm of human volunteers was 11.5 mg/sq cm/hr. An absorption rate of 0.145 mg/sq cm/min was observed after application to the forearm for 15 min, increasing to 0.22 and then decreasing to 0.185 mg/sq cm/min after 35 and 60 min, respectively. When 15 mL of methanol was applied to the forearm skin of human volunteers, there was some evidence of uptake based on increased

blood and urine methanol levels. The dermal flux for methanol in human skin (epidermis) in vitro is 8.29 mg/sq cm/hr. [Bingham, E.; Cohrssen, B.; Powell, C.H.; Patty's Toxicology Volumes 1-9 5th ed. John Wiley & Sons. New York, N.Y. (2001)., p. V6 p.382] **PEER REVIEWED**

Background levels of methanol and formic acid in the body are derived mainly from dietary and metabolic processes. A mean methanol blood level of 0.73 mg/L in 31 unexposed subjects (range 0.32 to 2.61 mg/L) was reported. [Bingham, E.; Cohrssen, B.; Powell, C.H.; Patty's Toxicology Volumes 1-9 5th ed. John Wiley & Sons. New York, N.Y. (2001)., p. V6 p.382] **PEER REVIEWED**

... 26 unexposed workers averaged 1.1 mg/L, with a range of < 0.6 to 2.9 mg/L. A mean of 0.25 mg/L methanol in expired breath of nine "normal" people (range 0.06 to 0.45 mg/L) was reported. Urine concentrations of methanol of up to 5 mg/L have been measured after ingestion of alcoholic beverages by subjects not otherwise exposed to methanol. [Bingham, E.; Cohrssen, B.; Powell, C.H.; Patty's Toxicology Volumes 1-9 5th ed. John Wiley & Sons. New York, N.Y. (2001)., p. V6 p.382] **PEER REVIEWED**

Methanol is rapidly absorbed from the gastrointestinal tract with peak absorption occurring in 30-60 min depending on the presence or absence of food in the stomach. [WHO; Environ Health Criteria 196: Methanol p.56 (1997). Available from, as of July 14, 2005: http://www.inchem.org/documents/ehc/ehc/ehc196.htm] **PEER REVIEWED**

...The absence of formic acid accumulation in the urine of 5 volunteers following 5 days of exposure to an atmosphere containing 260 mg/cu m (200 ppm) of methanol in a test chamber /was determined/. These results indicated that there was no day-to day accumulation of formic acid in urine in conjunction with 5 consecutive days of near-maximal permissible airborne methanol exposure and that measurement of formic acid in urine specimens collected 16 hr following cessation of exposure did not appear to reflect inhalation methanol exposure on the preceding day. [WHO; Environ Health Criteria 196: Methanol p.10 (1997). Available from, as of July 14, 2005: http://www.inchem.org/documents/ehc/ehc/ehc196.htm] **PEER 

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2/24/2011 htt p ://toxnet.nlm.nih. g ov/c g i- b in/sis/download.txtREVIEWED**

Skin absorption rate studies of methanol ranging from 0.031-0.241 mg/sq cm per min conducted in human volunteers showed that an average of 0.192 mg methanol/sq cm per min is absorbed through direct contact of the skin to methanol. [WHO; Environ Health Criteria 196: Methanol p.58 (1997). Available from, as of July 14, 2005: http://www.inchem.org/documents/ehc/ehc/ehc196.htm] **PEER REVIEWED**

After intake of small quantities of methanol (10-20 mL), human subjects showed no methanol in blood after 48 hr, and the concentration of formic acid in the urine was normal (6.5-12.8 mg%) within 24 hr. Following intake of large amounts of methanol (50 mL), methanol was found in the blood (250-1200 mg/L) after 48 hr. Formic acid was found in the blood (26-78 mg/L) as well as an increased excretion of formic acid in the urine (540-2050 mg/L), and up to 20,500 mg/L within 24 hr. Maximum excretion of formic acid was found to occur not later than the second or third day after intake of methanol. [WHO; Environ Health Criteria 196: Methanol p.58 (1997). Available from, as of July 14, 2005: http://www.inchem.org/documents/ehc/ehc/ehc196.htm] **PEER REVIEWED**

The rate of absorption into the skin has been found to be higher with M-85 (85% methanol-15% gasoline) than with pure methanol. The gasoline was suggested to act by drying out the skin allowing the methanol to be more readily absorbed. /M-85/ [WHO; Environ Health Criteria 196: Methanol p.58 (1997). Available from, as of July 14, 2005: http://www.inchem.org/documents/ehc/ehc/ehc196.htm] **PEER REVIEWED**

In separate studies, methanol (100 or 500 mg/kg) and 3H2O (20 uCi/kg) were administered intravenously on gestational days 20 and 14 to rats and on gestational day 18 to mice. The methanol concentration-time data were consistent with saturable maternal elimination and apparent first-order transfer between maternal and conceptual compartments. At distribution equilibrium, conceptual methanol concentrations exceeded those in the dam by approximately 25%. The initial rate of conceptual permeation of methanol was proportional to the reciprocal of maternal blood methanol concentration (r2 = 0.910). The data indicated that high circulating maternal methanol concentrations decrease the rate of presentation of methanol and 3H2O to the conceptus, and, depending on the severity of the decrease, fetal hypoxia could also result [WHO; Environ Health Criteria 196: Methanol p.60 (1997). Available from, as of July 14, 2005: http://www.inchem.org/documents/ehc/ehc/ehc196.htm] **PEER REVIEWED**

A fatal case involving a 41-yr-old man who had ingested a large quantity of methanol disclosed a broad distribution of methanol in postmortem tissues and fluids. The highest content of methanol was found in the kidney (5.13 g/kg) followed by the liver (4.18 g/kg), vitreous humor (3.9 g/L), heart (3.45 g/kg), urine (3.43 g/L), pericardial fluid (3.29 g/L), blood (2.84 g/L) and stomach contents (2.21 g/L). [WHO; Environ Health Criteria 196: Methanol p.106 (1997). Available from, as of July 18, 2005: http://www.inchem.org/documents/ehc/ehc/ehc196.htm] **PEER REVIEWED**

A study in 24 one-year-old infants measured blood methanol concentrations after oral exposure to aspartame. In a series of studies, 10 infants were exposed to 34 mg/kg aspartame (the estimated premarketing 99th percentile of adult daily ingestion), 6 infants were exposed to 50 mg/kg (termed a very high dose), and 8 infants received 100 mg/kg (described as an “abusive” dose). Methanol is a hydrolytic metabolite of aspartame accounting for 10% of aspartame consumed. Thus, these authors estimated the aspartame doses studied to be equivalent to ingestion of 3.4, 5, and 10 mg/kg bw methanol. Aspartame was administered via a cherry-flavored beverage. A fasting blood sample and three subsequent samples were obtained from each subject. The authors observed a positive correlation between aspartame dose and blood methanol level in the infants that was similar to that observed in a previous study of similar design and dose in adults. Mean blood methanol levels were at the limit of detection (3.5 mg/L) in infants administered 34 mg/kg aspartame. Infants administered aspartame at 50 mg/kg had peak blood methanol values of 3.0+/-1.0 mg/L 30-90 minutes after aspartame dosing. These values were essentially the same as those seen in adults, 3.4+/-1.2 mg/L, receiving an equivalent dose. The 8 infants administered the 100 mg/kg aspartame dose had a peak mean blood methanol value of 10.2+/-2.8 mg/L 90 minutes post dosing. In comparison, the mean blood methanol concentrations in 6 adults administered an equivalent dose of aspartame was 12.7+/-2.0 mg/L 60 minutes after dosing. While the responses in infants and adults at this dose were similar, the serum levels peaked earlier in adults and appeared to persist longer when one compared the area-under-the-curve throughout a 2.5-hour sampling period. [DHHS/NTP; NTP-CERHR Expert Panel Report on the Reproductive and Developmental Toxicity of Methanol p.10 (April 2002) NTP-CERHR-MeOH-02. Available from, as of July 20, 2005: http://cerhr.niehs.nih.gov/news/methanol/methanol_final.pdf] **PEER

REVIEWED**

Toxicokinetic studies were conducted following daily inhalation exposure to methanol vapor prior to and throughout pregnancy in adult female Macaca fascicularis monkeys. ...In a two-cohort study design, 48 females (24/cohort) were assigned to parallel exposure groups at 0 (control), 200, 600, or 1800 ppm methanol vapor for approximately 2.5 hr/day, 7 days/wk throughout breeding and pregnancy. Blood methanol at 30 min postexposure was monitored biweekly. The time course for the clearance of blood MeOH concentrations following exposure was characterized on four occasions: 

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2/24/2011 htt p ://toxnet.nlm.nih. g ov/c g i- b in/sis/download.txttwice during the prebreeding period and during mid- and late pregnancy. Average blood methanol concentrations at 30 min postexposure were 5, 11, and 35 ug/mL across all four toxicokinetic studies in the 200, 600 and 1800 ppm groups, respectively. Blood concentrations in the 200 ppm group were barely above basal (preexposure) blood methanol concentrations or those observed in the control group (approximately 3 ug/mL). Nonlinear elimination kinetics were observed in most of the 1800 ppm group females. There was a decrease in elimination half-life (7-20%) and an increase in clearance (30%) after 3-months of daily MeOH exposure compared to the initial exposure. There were no statistically significant changes in the first-order blood methanol half-life or clearance during pregnancy, but the mean distribution volume per kilogram body weight decreased by 22% and 17% in the 600 and 1800 ppm groups. Plasma formate levels did not differ between the methanol and control exposure groups. Plasma formate and serum folate concentrations increased slightly over the course of this study in both the exposed and control groups but these increases were not related to methanol exposure. [Burbacher TM et al; Neurotoxicology and Teratology 26 (2): 201-221 (2004)] **PEER REVIEWED** <a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15019954" target=new>PubMed Abstract

BIOLOGICAL HALF-LIFE: Biological half-life of methanol elimination in expired air is 1.5 hr after either oral or dermal application. [Dutkiewicz B; Int Congr Ser- Excerpta Med 440 (Ind Environ Xenobiotics): 106-9 (1978)] **PEER

REVIEWED**

... Experiments were made during the morning after /human volunteers/ had consumed 1000-1500 mL red wine (9.5% weight/volume ethanol, 100 mg/L methanol) the previous evening. The washout of methanol from the body coincided with the onset of hangover. The concentrations of ethanol and methanol in blood were determined indirectly by analysis of end-expired alveolar air. In the morning when blood-ethanol dropped below the Km of liver alcohol dehydrogenase of about 100 mg/L (2.2 mM), the disappearance half-life of ethanol was 21, 22, 18 and 15 min in 4 test subjects, respectively. The corresponding elimination half-lives of methanol were 213, 110, 133 and 142 min in these same individuals. ... [Jones AW; Pharmacol Toxicol 60 (3): 217-20 (1987)] **PEER REVIEWED** <a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=3588516" target=new>PubMed Abstract

Urinary methanol levels decreased exponentially with a half-life of about 2.5 to 3 hr in four volunteers exposed by inhalation to 102, 205, or 300 mg/cu m for 8 hr. [Bingham, E.; Cohrssen, B.; Powell, C.H.; Patty's Toxicology Volumes 1-9 5th ed. John Wiley & Sons. New York, N.Y. (2001)., p. V6 p.381] **PEER REVIEWED**

In rats exposed by inhalation to 200, 1200, and 2000 ppm methanol for 6 hr... the blood half-lives were 0.8, 2.3, and 2.4 hr at 200, 1200, and 2000 ppm, respectively. [Bingham, E.; Cohrssen, B.; Powell, C.H.; Patty's Toxicology Volumes 1-9 5th ed. John Wiley & Sons. New York, N.Y. (2001)., p. V6 p.375] **PEER REVIEWED**

... The primate half lives after 200, 1200, and 2000 ppm were 2.4, 3.3, and 3.5 hr, respectively. [Bingham, E.; Cohrssen, B.; Powell, C.H.; Patty's Toxicology Volumes 1-9 5th ed. John Wiley & Sons. New York, N.Y. (2001)., p. V6 p.375] **PEER REVIEWED**

When methanol was administered orally to three volunteers at doses of 2.4, 4.0, or 5.6 g, elimination of methanol from the blood followed first-order kinetics with a half-time of about 3 hr. [Bingham, E.; Cohrssen, B.; Powell, C.H.; Patty's Toxicology Volumes 1-9 5th ed. John Wiley & Sons. New York, N.Y. (2001)., p. V6 p.536] **PEER REVIEWED**

MECHANISM OF ACTION: ...The metabolic mechanisms of methanol toxicity /are/ reviewed. ... It is noted that the most severe toxicty occurs many hours following peak blood and tissue methanol concentrations so that these do not necessarily provide an accurate indication of toxicity. Individual differences are seen both in this latent period and in individual susceptibility to methanol. This susceptibility may depend on the activity of folic acid requiring metabolic reactions involved in formate metabolism, formate being an intermediate produced during methanol oxidation and responsible for many toxic effects of methanol. Studies of the characteristics of methanol poisoning in non-primates and monkeys are examined. Despite the ingestion of lethal doses of methanol, non-primates generally do not develop significant metabolic acidosis nor impairment of vision, and no consistent histopathology has been demonstrated in these species. In monkeys, results suggest that the latent period represents a period of compensated metabolic acidosis; when compensatory mechanisms are exhausted, blood pH begins to drop. Formate accumulates and produces acidosis in the methanol poisoned monkey, but not in the rat, apparently

due to a slower rate of formate metabolism to carbon dioxide in the monkey. ... Studies demonstrating the role of alcohol dehydrogenase in methanol metabolism in the monkey are reported; however, the catalase/peroxidative system which participates in methanol metabolism in rats apparently does not function in the monkey. Formaldehyde and formate metabolism are also examined. The regulation of the rate of formate metabolism is governed by regulation of the hepatic tetrahydrofolate concentrations. ... Further research is needed to determine what step or process it is which places the primate at a distinct liability in the 

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2/24/2011 htt p ://toxnet.nlm.nih. g ov/c g i- b in/sis/download.txtmetabolic disposition of one carbon moieties. [Tephly TR, Martin KE; Food Sci Technol 12: 111-40 (1984)] **PEER REVIEWED**

Methanol toxicity is observed in monkeys and humans but is not seen in rats or mice. The expression of methanol poisoning is related to the ability of an animal to metabolize formate to carbon dioxide. Since the rate of formate oxidation is related to hepatic tetrahydrofolate content and the activites of folate dependent enzymes, studies were designed to determine hepatic concentrations of hepatic tetrahydrofolate and activites of folate dependent enzymes of human liver and livers of species considered insensitive to methanol poisoning. An excellent correlation between hepatic tetrahydrofolate and maximal rates of formate oxidation has been observed. In human liver, levels were only 50% of those observed for rat liver and similar to those found in monkey liver. Total folate was also lower (60% decreased) in human liver than that found in rat or monkey liver. Interestingly, mouse liver contains much higher hepatic tetrahydrofolate and total folate than rat or monkey liver. This is consistent with higher formate oxidation rates in this species. A second important observation has been made. 10-Formyltetrahydrofolate dehydrogenase activity, the enzyme catalyzing the final step of formate oxidation to carbon dioxide, was markedly reduced in both monkey and human liver. Thus, two mechanisms may be operative in explaining low formate oxidation in species susceptible to methanol toxicity, low hepatic tetahydrofolate levels and reduced hepatic 10-formyltetrahydrofolate dehydrogenase activity. [Johlin FC et al; Mol Pharmacol 31 (5): 557-61 (1987)] **PEER REVIEWED** <a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=3574297" target=new>PubMed Abstract

Formic acid, the toxic metabolite of methanol, has been hypothesized to produce retinal and optic nerve toxicity by disrupting mitochondrial energy production. It has been shown in vitro to inhibit the activity of cytochrome oxidase, a vital component of the mitochondrial electron transport chain involved in ATP synthesis. Inhibition occurs subsequent to the binding of formic acid to the ferric heme iron of cytochrome oxidase, and the apparent inhibition constant is between 5 and 30 mM. Concentrations of formate present in the blood and tissues of methanol-intoxicated humans, non-human primates and rodent models of methanol-intoxication are within this range. Studies conducted in

methanol-sensitive rodent models have revealed abnormalities in retinal and optic nerve function and morphology, consistent with the hypothesis that formate acts as a mitochondrial toxin. In these animal models, formate oxidation is selectively inhibited by dietary or chemical depletion of folate coenzymes, thus allowing formate to accumulate to toxic concentrations following methanol administration. Methanol-intoxicated rats developed formic acidemia, metabolic acidosis and visual toxicity analogous to the human methanol poisoning syndrome. [WHO; Environ Health Criteria 196: Methanol p.94 (1997). Available from, as of July 18, 2005: http://www.inchem.org/documents/ehc/ehc/ehc196.htm]

**PEER REVIEWED**

Visual dysfunction was measured as reduction in the flash evoked cortical potential (FEP) and electroretinogram (ERG). The FEP is a measure of the functional integrity of the primary visual pathway from the retina to the visual cortex and the ERG is a global measure of retinal function in response to illumination. The FEP was progressively diminished in methanol intoxicated rats, indicative of a disruption of neuronal conduction along the primary visual pathway from the retina to the visual cortex. ERG analysis in methanol-intoxicated rats revealed a significant early deficit in b-wave amplitude, followed by a temporally delayed lesser reduction in a-wave amplitude. The b-wave of the ERG is generated by depolarization of the Muller glial cells and reflects synaptic activity at the level of the bipolar cells. The b-wave of the ERG is extremely sensitive to conditions that interfere with retinal energy metabolism and is reduced or abolished following brief ischemia or the administration of metabolic poisons. Both

FEP and ERG alterations occurred at the same time as accumulation of blood formate, indicative of a causal relationship between formate-induced

metabolic and visual disturbances. Similar ERG reductions have been reported in methanol-intoxicated primates and in human methanol intoxication. [WHO; Environ Health Criteria 196: Methanol p.95 (1997). Available from, as of July 18, 2005: http://www.inchem.org/documents/ehc/ehc/ehc196.htm] **PEER REVIEWED**

In addition to neurofunctional changes, bioenergetic and morphological alterations indicative of formate-induced disruption of retinal energy

metabolism have been documented in methanol-intoxicated rats. Morphological studies, coupled with cytochrome oxidase histochemistry, revealed generalized retinal edema, photoreceptor and /retinal pigment epithelium/ (RPE) vacuolation, mitochondrial swelling and a reduction in cytochrome oxidase activity in photoreceptor mitochondria from methanol intoxicated rats. The most striking structural alterations observed in the

retinas of methanol-intoxicated rats were vacuolation and mitochondrial swelling in inner segments of the photoreceptor cells. Photoreceptor mitochondria from methanol-intoxicated rats were swollen and expanded to disrupted cristae and showed no evidence of cytochrome oxidase reaction product. In contrast, photoreceptor mitochondria from control animals showed normal morphology with well-defined cristae and were moderately reactive for cytochrome oxidase reaction product. These findings are consistent with disruption of ionic homoeostasis in the photoreceptors, secondary to inhibition of mitochondrial function. Biochemical measurements also showed a significant reduction in retinal and brain 

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2/24/2011 htt p ://toxnet.nlm.nih. g ov/c g i- b in/sis/download.txtcytochrome oxidase activity and ATP concentrations in methanol-intoxicated rats relative to control animals. Surprisingly, no differences from control values were observed in hepatic, renal or cardiac cytochrome oxidase activity or ATP concentrations in methanol-intoxicated rats. The reduction in retinal function, inhibition of retinal, optic nerve and brain cytochrome oxidase activity, depletion of retinal and brain ATP concentrations, and mitochondrial disruption produced in methanol-intoxicated rats are consistent with the hypothesis that formate acts as a mitochondrial toxin with selectivity for the retina and brain. [WHO; Environ Health Criteria 196: Methanol p.96 (1997). Available from, as of July 18, 2005: http://www.inchem.org/documents/ehc/ehc/ehc196.htm]

**PEER REVIEWED**

Role of free radicals in methanol toxicity was evaluated in methanol treated albino rats. Methanol intoxication increased lipid peroxidation and depleted the free radical scavenging enzyme systems. The free radical quenching effect of vitamin E protected the animals from methanol induced free radical damage. [Paula EM et al; Indian J Physiol Pharmacol 47 (2): 207-11 (2003)] **PEER REVIEWED** <a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15255626&query_hl=10" target=new>PubMed Abstract

The initiating effect in the ocular toxicity of formic acid is believed to involve the inhibition of cytochrome oxidase, which is located in the mitochondria and is involved in oxidative phosphorylation. [Bingham, E.; Cohrssen, B.; Powell, C.H.; Patty's Toxicology Volumes 1-9 5th ed. John Wiley & Sons. New York, N.Y. (2001)., p. V6 p.380] **PEER REVIEWED**

INTERACTIONS: ...Pyrazole and 3-amino-1,2,4-triazole... are potent inhibitors of alcohol dehydrogenase and catalase... both are active in vivo. ...Administered separately or together... /to rats/. Findings confirmed... that 3-amino-1,2,4-triazole... decreased rate of carbon dioxide production. ...Pyrazole... substantially reduced oxidation of methanol to carbon dioxide. [The Chemical Society. Foreign Compound Metabolism in Mammals Volume 3. London: The Chemical Society, 1975., p. 624] **PEER REVIEWED**

Ethanol is used to inhibit the conversion of methanol to its highly toxic metabolite, formic acid... . [Hardman, J.G., L.E. Limbird, P.B., A.G. Gilman. Goodman and Gilman's The Pharmacological Basis of Therapeutics. 10th ed. New York, NY: McGraw-Hill, 2001., p. 78] **PEER REVIEWED**

Chronic combined exposure to methanol and carbon monoxide has been reported as a causative factor of cerebral atherosclerosis. [International Labour Office. Encyclopedia of Occupational Health and Safety. Vols. I&II. Geneva, Switzerland: International Labour Office, 1983., p. 1357] **PEER REVIEWED**

... Dinitrogen oxide inhibited the oxidation of formate generated from the metabolism of methanol resulting in the development of severe metabolic acidosis and high blood formate levels in these animals compared with air breathing monkeys administered the same dose of methanol. Treatment of dinitrogen oxide exposed monkeys with repetitive doses of methionine (100 mg/kg 10, 12, and 14 hr after methanol exposure) reversed the effects of dinitrogen oxide on formate oxidation resulting in a marked decrease in blood formate levels and an increase in the rate of (14)carbon dioxide

formation from methanol. Methionine treatment also reversed the development of metabolic acidosis and bicarbonate depletion observed in dinitrogen oxide exposed monkeys. Thus, hepatic methionine synthetase is important in the regulation of tetrahydrofolate dependent metabolism in the monkey and the generation of this enzyme is a major factor in determining the sensitivity of a species to methanol poisoning. [Eells JT et al; J Pharm Exp Ther 227 (2): 349-53 (1983)] **PEER REVIEWED**

Inhaled methanol potentiated the hepatotoxicity produced by carbon tetrachloride in adult male F-344 rats. Rats were exposed to methanol (0 or 13,000 mg/cu m) 10000 ppm for 6 hr, then treated 24 hr later with oral CCl4 (0.075 mL/kg). CCl4 alone produced a low level of hepatotoxicity within 3 days. Methanol plus CCl4 resulted in marked increases in serum aspartate aminotransferase and alanine aminotransferase that lasted for 7 days. Methanol also exacerbated the histological evidence of CCl4-induced centrilobular degeneration and necrosis. Methanol exposure by inhalation induced cytochrome P4502E1 (CYP2E1), which appeared to be the principal toxicokinetic mechanism underlying methanol potentiation of carbon tetrachloride hepatotoxicity. [WHO; Environ Health Criteria 196: Methanol p.93 (1997). Available from, as of July 18, 2005: http://www.inchem.org/documents/ehc/ehc/ehc196.htm] **PEER REVIEWED**

When dichloromethane (DCM) is metabolized carbon monoxide is formed, leading to increased carboxyhemoglobin (COHb) levels in blood. ...In rats pretreated with methanol, methanol doses of 790-6330 mg/kg (24.7-198 mmol/kg) stimulated increased metabolism of DCM, as seen by further increases in COHb levels. When methanol was administered simultaneously with DCM, a decrease in COHb formation was seen at methanol doses of 4736 to 7900 mg/kg (148-247 mmol/kg) but not at 3162 mg/kg (98.8 mmol/kg). Thus methanol can interact with DCM metabolism both by induction and by competitive inhibition, the latter only at very high doses. [WHO; Environ Health Criteria 196: Methanol p.93 (1997). Available from, as of July 18, 2005: http://www.inchem.org/documents/ehc/ehc/ehc196.htm] **PEER

REVIEWED** 

# Iris Camacho, 6308MM Pa g e 39 of 69

2/24/2011 htt p ://toxnet.nlm.nih. g ov/c g i- b in/sis/download.txtThis research was undertaken to determine potential interactions among chemical and physical agents. Radiofrequency (RF) radiation is used in numerous workplaces, and many workers are concurrently exposed to RF radiation and various chemicals. The developmental toxicity of RF radiation is associated with the degree and duration of hyperthermia induced by the exposure. Previous animal research indicates that hyperthermia induced by an elevation in ambient temperature can potentiate the toxicity and teratogenicity of some chemical agents. We previously demonstrated that combined exposure to RF radiation (10 MHz) and the industrial solvent, 2-methoxyethanol (2ME), enhanced teratogenicity in rats. Interactions were noted at even the lowest levels of 2ME tested, but only at hyperthermic levels of RF radiation. The purpose of the present research is to investigate if the interactive effects noted for RF radiation and 2ME are unique to these agents, or if similar interactions might be seen with other chemicals. Because methanol is widely used as a solvent as well as fuel additive, and, at high levels, is teratogenic in animals, we selected methanol as a chemical to address generalizability. Based on the literature and our pilot studies, 0, 2, or 3 g/kg methanol (twice, at 6-hr intervals) were administered on gestation day 9 or 13 to groups of 10 Sprague-Dawley rats. Dams treated on day 9 were given methanol and exposed to RF radiation sufficient to maintain colonic temperature at 41 deg C for 60 minutes (or sham). Those treated on day 13 were given methanol plus either 0 or 100 mg/kg 2ME. Because we observed that methanol produced hypothermia, some groups were given the initial dose of methanol concurrently with the RF or 2ME, and others were given the first dose of methanol 1.5 hours prior to RF or 2ME. Dams were sacrificed on gestation day 20, and the fetuses were examined for external malformations. The results indicate that RF radiation or methanol on day 9 increased the incidence of resorbed fetuses, but no interactive effects were observed. The resorptions were highest in groups given the experimental treatments 1.5 hours apart. The higher dose of methanol also reduced fetal weights. Administration of 2ME or methanol on day 13 increased the rate of malformations, and there was evidence of a positive interaction between 2ME and methanol. Fetal weights were reduced by 2ME and methanol alone, but no interaction was observed. Also, separation of the dosing with the teratogens did not affect the results. [Nelson BK et al; Int J Toxicol 20 (2): 89-100 (2001)] **PEER REVIEWED** <a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=11354470&query_hl=46" target=new>PubMed Abstract

An attempt has been made to study the histological and ultrastructural changes in the liver of rats caused by individual and combined treatment of three industrial solvents viz. xylene, toulene and methyl alcohol. Results show that methyl alcohol is more hepatotoxic than xylene and toluene. A mixture of these solvents is also hepatotoxic. It causes peculiar ultrastructural changes viz. involution of nuclear membrane and irregular arrangement of mitochondrial cristae. It is concluded that a weak interaction takes place at the site of their metabolism expressed as weak antagonism. Histological changes thus noted do not strictly correspond with functional changes as observed during earlier investigations. [Rana S VS, Kumar S; J of Environ Biol 18 (2): 185-90 (1997)] **PEER REVIEWED**

The drug 4-methylpyrazole (4-MP; fomepizole) is a competitive ADH inhibitor and an effective antidote for methanol and ethylene glycol poisoning. [Sullivan, J.B., Krieger G.R. (eds). Clinical Environmental Health and Toxic Exposures. Second edition. Lippincott Williams and Wilkins, Philadelphia, Pennsylvania 1999., p. 1179] **PEER REVIEWED**

It has been suggested that the metabolic acidosis due to methanol might be

exacerbated in individuals with diabetes since it is well known that these patients suffer from diabetic ketoacidosis. However, there are no clinical or experimental data on any interaction between methanol acidosis and diabetic ketoacidosis. [WHO; Environ Health Criteria 196: Methanol p.113 (1997). Available from, as of July 19, 2005: http://www.inchem.org/documents/ehc/ehc/ehc196.htm] **PEER REVIEWED**

PHARMACOLOGY:

INTERACTIONS: ...Pyrazole and 3-amino-1,2,4-triazole... are potent inhibitors of alcohol dehydrogenase and catalase... both are active in vivo. ...Administered separately or together... /to rats/. Findings confirmed... that 3-amino-1,2,4-triazole... decreased rate of carbon dioxide production. ...Pyrazole... substantially reduced oxidation of methanol to carbon dioxide. [The Chemical Society. Foreign Compound Metabolism in Mammals Volume 3. London: The Chemical Society, 1975., p. 624] **PEER REVIEWED**

Ethanol is used to inhibit the conversion of methanol to its highly toxic metabolite, formic acid... . [Hardman, J.G., L.E. Limbird, P.B., A.G. Gilman. Goodman and Gilman's The Pharmacological Basis of Therapeutics. 10th ed. New York, NY: McGraw-Hill, 2001., p. 78] **PEER REVIEWED**

Chronic combined exposure to methanol and carbon monoxide has been reported as a causative factor of cerebral atherosclerosis. [International Labour Office. Encyclopedia of Occupational Health and Safety. Vols. I&II. Geneva, Switzerland: International Labour Office, 1983., p. 1357] **PEER REVIEWED** 

# Iris Camacho, 6308MM Pa g e 40 of 69

2/24/2011 htt p ://toxnet.nlm.nih. g ov/c g i- b in/sis/download.txt... Dinitrogen oxide inhibited the oxidation of formate generated from the metabolism of methanol resulting in the development of severe metabolic acidosis and high blood formate levels in these animals compared with air breathing monkeys administered the same dose of methanol. Treatment of dinitrogen oxide exposed monkeys with repetitive doses of methionine (100 mg/kg 10, 12, and 14 hr after methanol exposure) reversed the effects of dinitrogen oxide on formate oxidation resulting in a marked decrease in blood formate levels and an increase in the rate of (14)carbon dioxide

formation from methanol. Methionine treatment also reversed the development of metabolic acidosis and bicarbonate depletion observed in dinitrogen oxide exposed monkeys. Thus, hepatic methionine synthetase is important in the regulation of tetrahydrofolate dependent metabolism in the monkey and the generation of this enzyme is a major factor in determining the sensitivity of a species to methanol poisoning. [Eells JT et al; J Pharm Exp Ther 227 (2): 349-53 (1983)] **PEER REVIEWED**

Inhaled methanol potentiated the hepatotoxicity produced by carbon tetrachloride in adult male F-344 rats. Rats were exposed to methanol (0 or 13,000 mg/cu m) 10000 ppm for 6 hr, then treated 24 hr later with oral CCl4 (0.075 mL/kg). CCl4 alone produced a low level of hepatotoxicity within 3 days. Methanol plus CCl4 resulted in marked increases in serum aspartate aminotransferase and alanine aminotransferase that lasted for 7 days. Methanol also exacerbated the histological evidence of CCl4-induced centrilobular degeneration and necrosis. Methanol exposure by inhalation induced cytochrome P4502E1 (CYP2E1), which appeared to be the principal toxicokinetic mechanism underlying methanol potentiation of carbon tetrachloride hepatotoxicity. [WHO; Environ Health Criteria 196: Methanol p.93 (1997). Available from, as of July 18, 2005: http://www.inchem.org/documents/ehc/ehc/ehc196.htm] **PEER REVIEWED**

When dichloromethane (DCM) is metabolized carbon monoxide is formed, leading to increased carboxyhemoglobin (COHb) levels in blood. ...In rats pretreated with methanol, methanol doses of 790-6330 mg/kg (24.7-198 mmol/kg) stimulated increased metabolism of DCM, as seen by further increases in COHb levels. When methanol was administered simultaneously with DCM, a decrease in COHb formation was seen at methanol doses of 4736 to 7900 mg/kg (148-247 mmol/kg) but not at 3162 mg/kg (98.8 mmol/kg). Thus methanol can interact with DCM metabolism both by induction and by competitive inhibition, the latter only at very high doses. [WHO; Environ Health Criteria 196: Methanol p.93 (1997). Available from, as of July 18, 2005: http://www.inchem.org/documents/ehc/ehc/ehc196.htm] **PEER

REVIEWED**

This research was undertaken to determine potential interactions among chemical and physical agents. Radiofrequency (RF) radiation is used in numerous workplaces, and many workers are concurrently exposed to RF radiation and various chemicals. The developmental toxicity of RF radiation is associated with the degree and duration of hyperthermia induced by the exposure. Previous animal research indicates that hyperthermia induced by an elevation in ambient temperature can potentiate the toxicity and teratogenicity of some chemical agents. We previously demonstrated that combined exposure to RF radiation (10 MHz) and the industrial solvent, 2-methoxyethanol (2ME), enhanced teratogenicity in rats. Interactions were noted at even the lowest levels of 2ME tested, but only at hyperthermic levels of RF radiation. The purpose of the present research is to investigate if the interactive effects noted for RF radiation and 2ME are unique to these agents, or if similar interactions might be seen with other chemicals. Because methanol is widely used as a solvent as well as fuel additive, and, at high levels, is teratogenic in animals, we selected methanol as a chemical to address generalizability. Based on the literature and our pilot studies, 0, 2, or 3 g/kg methanol (twice, at 6-hr intervals) were administered on gestation day 9 or 13 to groups of 10 Sprague-Dawley rats. Dams treated on day 9 were given methanol and exposed to RF radiation sufficient to maintain colonic temperature at 41 deg C for 60 minutes (or sham). Those treated on day 13 were given methanol plus either 0 or 100 mg/kg 2ME. Because we observed that methanol produced hypothermia, some groups were given the initial dose of methanol concurrently with the RF or 2ME, and others were given the first dose of methanol 1.5 hours prior to RF or 2ME. Dams were sacrificed on gestation day 20, and the fetuses were examined for external malformations. The results indicate that RF radiation or methanol on day 9 increased the incidence of resorbed fetuses, but no interactive effects were observed. The resorptions were highest in groups given the experimental treatments 1.5 hours apart. The higher dose of methanol also reduced fetal weights. Administration of 2ME or methanol on day 13 increased the rate of malformations, and there was evidence of a positive interaction between 2ME and methanol. Fetal weights were reduced by 2ME and methanol alone, but no interaction was observed. Also, separation of the dosing with the teratogens did not affect the results. [Nelson BK et al; Int J Toxicol 20 (2): 89-100 (2001)] **PEER REVIEWED** <a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=11354470&query_hl=46" target=new>PubMed Abstract

An attempt has been made to study the histological and ultrastructural changes in the liver of rats caused by individual and combined treatment of three industrial solvents viz. xylene, toulene and methyl alcohol. Results show that methyl alcohol is more hepatotoxic than xylene and toluene. A mixture of these solvents is also hepatotoxic. It causes peculiar ultrastructural changes viz. involution of nuclear membrane and irregular arrangement of mitochondrial cristae. It is concluded that a weak interaction takes place at the site of their metabolism expressed as 

# Iris Camacho, 6308MM Pa g e 41 of 69

2/24/2011 htt p ://toxnet.nlm.nih. g ov/c g i- b in/sis/download.txtweak antagonism. Histological changes thus noted do not strictly correspond with functional changes as observed during earlier investigations. [Rana S VS, Kumar S; J of Environ Biol 18 (2): 185-90 (1997)] **PEER REVIEWED**

The drug 4-methylpyrazole (4-MP; fomepizole) is a competitive ADH inhibitor and an effective antidote for methanol and ethylene glycol poisoning. [Sullivan, J.B., Krieger G.R. (eds). Clinical Environmental Health and Toxic Exposures. Second edition. Lippincott Williams and Wilkins, Philadelphia, Pennsylvania 1999., p. 1179] **PEER REVIEWED**

It has been suggested that the metabolic acidosis due to methanol might be

exacerbated in individuals with diabetes since it is well known that these patients suffer from diabetic ketoacidosis. However, there are no clinical or experimental data on any interaction between methanol acidosis and diabetic ketoacidosis. [WHO; Environ Health Criteria 196: Methanol p.113 (1997). Available from, as of July 19, 2005: http://www.inchem.org/documents/ehc/ehc/ehc196.htm] **PEER REVIEWED**

MINIMUM FATAL DOSE LEVEL: The minimum lethal dose of methanol in the absence of medical treatment is between 0.3 and 1 g/kg. [Environmental Health Criteria 196: Methanol pp. 8 (1997) by the International Programme on Chemical Safety (IPCS) under the joint sponsorship of the United Nations Environment Programme, the International Labour Organisation and the World Health Organization.]

**PEER REVIEWED**

ENVIRONMENTAL FATE & EXPOSURE:

ENVIRONMENTAL FATE/EXPOSURE SUMMARY: Methanol's production and use as a solvent, fuel additive, and in the production of formaldehyde, acetic acid, and methyl tertiary butyl ether (MTBE) may result in its release to the environment through various waste streams. Methanol has been identified as a natural emission product from various plants and as a biological decomposition product of biological wastes and sewage. If released to the atmosphere, a vapor pressure of 127 mm Hg at 25 deg C indicates that methanol will exist solely in the vapor phase. Vapor phase methanol is degraded in the atmosphere by reaction with photochemically-produced hydroxyl radicals; the half-life for this reaction in air is estimated to be 17 days. If released to soil, methanol is expected to have very high mobility based upon an estimated Koc of 1. Volatilization from moist soil surfaces is expected to be an important fate process based upon a Henry's Law constant of 4.55X10-6 atm-cu m/mole. Methanol may also volatilize from dry soils based upon it vapor pressure. Biodegradation of methanol in soils is expected to occur rapidly based on half-lives in a sandy silt loam from Texas and a sandy loam from Mississippi of 1 and 3.2 days, respectively. If released into water, methanol is not expected to adsorb to suspended solids and sediment based upon the estimated Koc. Volatilization from water surfaces is expected to be an important fate process based upon this compound's Henry's Law

constant. Estimated volatilization half-lives for a model river and model lake are 3 and 35 days, respectively. Biodegradation is expected to occur in natural waters since methanol is degraded quickly in soils and was biodegraded rapidly in various aqueous screening tests using sewage seed or activated sludge. BCF values of less than 10, measured in fish suggests bioconcentration in aquatic organisms is low. Hydrolysis of methanol and photolysis in sunlit surface waters are not expected since methanol lacks functional groups that are susceptible to hydrolysis or photolysis under environmental conditions. Occupational exposure to methanol may occur through inhalation and dermal contact with this compound at workplaces where methanol is produced or used. Monitoring data indicate that the general population may be exposed to methanol via inhalation of ambient air, and ingestion of food and drinking water. (SRC) **PEER REVIEWED**

PROBABLE ROUTES OF HUMAN EXPOSURE:

STUDY OF WOOD HEEL INDUSTRY IN MA SHOWED AVG METHANOL VAPOR CONCN RANGING FROM 160-170 PPM, WITH NO DEFINITE EVIDENCE OF INJURY TO EXPOSED WORKERS ... CONCN BETWEEN 400 & 1000 PPM IN SPIRIT DUPLICATING PROCESSES /WERE REPORTED/. NO MENTION WAS MADE OF SYMPTOMS OR COMPLAINTS, BUT THESE CONCN WERE CONSIDERED EXCESSIVE. ... [American Conference of Governmental Industrial Hygienists. Documentation of the Threshold Limit Values and Biological Exposure Indices. 5th ed. Cincinnati, OH: American Conference of Governmental Industrial Hygienists, 1986., p. 372] **PEER REVIEWED**

ALTHOUGH INDIVIDUAL RESPONSES OF MAN TO METHYL ALCOHOL MAY VARY

CONSIDERABLY, INDUSTRIAL EXPOSURES ARE NOT VERY HAZARDOUS IF CONCN ARE MAINTAINED WITHIN UPPER LIMIT OF 200 PPM BY PROPER VENTILATION. [Clayton, G. D. and F. E. Clayton (eds.). Patty's Industrial Hygiene and Toxicology: Volume 2A, 2B, 2C: Toxicology. 3rd ed. New York: John Wiley Sons, 1981-1982., p. 4541] **PEER REVIEWED**

NIOSH (NOES Survey 1981-1983) has statistically estimated that 1,219,371 workers (295,849 of these are female) are potentially exposed to methanol in the US(1). Occupational exposure to methanol may occur through inhalation and dermal contact with this compound at workplaces where methanol is produced or used(SRC). Monitoring data indicate that the general population may be exposed to methanol via inhalation of ambient air, ingestion of food and drinking water(SRC). [(1) NIOSH; International Safety Cards. Methanol. 67-56-1. Available at 

# Iris Camacho, 6308MM Pa g e 42 of 69

2/24/2011 htt p ://toxnet.nlm.nih. g ov/c g i- b in/sis/download.txthttp://www.cdc.gov/niosh/ipcs/nicstart.html as of Jul 1, 2005.] **PEER

REVIEWED**

BODY BURDEN: Methanol was detected in 1 of 12 samples of human milk collected from volunteers in 4 USA cities(1). Methanol has been detected in expired human air(2,3,4); in one study, it was detected in 3.6% of 387 expired air samples collected from 54 volunteers at a geometric mean concn of 0.549 ng/l(4). [(1) Pellizzari ED et al; Bull Environ Contam Toxicol 28: 322-8 (1982) (2) Krotosynski B; J Chromat Sci 15: 239-44 (1977) (3) Krotosynski BK, O'Neill HJ; J Environ Sci Health Part A-Environ Sci Eng 17: 855-83 (1982) (4) Krotosynski BK et al; J Anal Toxicol 3: 255-43 (1979)] **PEER

REVIEWED**

NATURAL POLLUTION SOURCES: Methanol is found in wood. [Verschueren, K. Handbook of Environmental Data of Organic Chemicals. 2nd ed. New York, NY: Van Nostrand Reinhold Co., 1983., p. 430] **PEER REVIEWED**

A small amount of methanol is found in the expired breath of normal subjects, possibly by endogenous metabolic production. [Haddad, L.M. and Winchester, J.F. Clinical Management of Poisoning and Drug Overdosage. Philadelphia, PA: W.B. Saunders Co., 1983., p. 393] **PEER REVIEWED**

Methanol has been identified as a volatile emission product from evergreen cypress trees(1). Methanol is formed during biological decomposition of biological wastes, sewage, and sludges(2). Natural emission sources include volcanic gases, vegetation, microbes, and insects(3). [(1) Isidorov VA et al; Atmos Environ 19: 1-8 (1985) (2) Abrams EF et al; Identification of Organic Compounds in Effluents from Industrial Sources EPA- 560/3-75-002 p. 102 (1975) (3) Graedel TE et al; Atmospheric Chemical Compounds. Sources, Occurrence, and Bioassay. Orlando, FL: Academic Press p. 232 (1986)] **PEER REVIEWED**

Some distilled fruit spirits contain, normally, high quantities of methanol. ... [Bindler F et al; Food Addit Contam 5 (3): 343-51 (1988)]

**PEER REVIEWED** <a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=3396738" target=new>PubMed Abstract

ARTIFICIAL POLLUTION SOURCES: Methanol's production and use as a solvent, fuel additive, and in the production of formaldehyde, acetic acid, and methyl tertiary butyl ether (MTBE)(1) may result in its release to the environment through various waste streams(SRC). The largest anthropogenic source of methanol release to the environment is evaporation from solvent uses which amounts to an estimated 1.1 billion lb annually(2). Annual emission releases from methanol production, end-product mfg, and storage/handling have been estimated to be 68, 49, and 12 million lb, respectively(2). [(1) English A et al; in Kirk-Othmer Encycl Cheml Technol 4th ed Kroschwitz JI, ed. NY, NY John Wiley and Sons 16: 537-56 (1995) (2) USEPA; Chemical Hazard Information Profiles (CHIPS). USEPA-560/11-80-011 p. 196-7 (1980)] **PEER

REVIEWED**

ENVIRONMENTAL FATE: TERRESTRIAL FATE: Based on a classification scheme(1), an estimated Koc value of 1(SRC), determined from a structure estimation method(2), indicates that methanol is expected to have very high mobility in soil(SRC). Volatilization of methanol from moist soil surfaces is expected to be an important fate process(SRC) given a Henry's Law constant of 4.55X10-6 atm-cu m/mole(3). The potential for volatilization of methanol from dry soil surfaces may exist(SRC) based upon a vapor pressure of 127 mm Hg(4). Biodegradation is expected to be an important fate process for methanol based on half-lives of 1 and 3.2 days measured in a sandy silt loam and sandy loam from Texas and Mississippi, respectively(5). [(1) Swann RL et al; Res Rev 85: 17-28 (1983) (2) Meylan WM et al; Environ Sci Technol 26: 1560-67 (1992) (3) Gaffney JS et al; Environ Sci Technol 21: 519-23 (1987) (4) Boublik T et al, eds; The Vapour Pressures of Pure Substances. 2nd rev ed. Amsterdam: Elsevier (1984) (5) Loehr RC; Treatability potential for EPA listed hazardous wastes in soil. USEPA. Robert S. Kerr Environ. Res. Lab., ADA, OK. EPA/600/2-89/011 (1989)]

**PEER REVIEWED**

AQUATIC FATE: Based on a classification scheme(1), an estimated Koc value of 1(SRC), determined from a structure estimation method(2), indicates that methanol is not expected to adsorb to suspended solids and sediment(SRC). Volatilization from water surfaces is expected(3) based upon a Henry's Law constant of 4.55X10-6 atm-cu m/mole(4). Using this Henry's Law constant and an estimation method(3), volatilization half-lives for a model river and model lake are 3 and 35 days, respectively(SRC). According to a classification scheme(5), a BCF of less than 10 measured in fish(6), suggests bioconcentration in aquatic organisms is low(SRC). Hydrolysis and photolysis in sunlit surface waters is not expected to be an important environmental fate process for methanol since this compound lacks functional groups that hydrolyze or absorb light under environmentally relevant conditions. Methanol has been shown to undergo rapid biodegradation in a variety of screening studies using sewage seed and activated sludge inoculum(7-9), which suggests that biodegradation will occur in aquatic environments. [(1) Swann RL et al; Res Rev 85: 17-28 (1983) (2) Meylan WM et al; Environ Sci Technol 26: 1560-67 (1992) (3) Lyman WJ et al; Handbook of Chemical Property 

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2/24/2011 htt p ://toxnet.nlm.nih. g ov/c g i- b in/sis/download.txtEstimation Methods. Washington, DC: Amer Chem Soc pp. 4-9, 15-1 to 15-29 (1990) (4) Gaffney JS et al; Environ Sci Technol 21: 519-23 (1987) (5) Franke C et al; Chemosphere 29: 1501-14 (1994) (6) Freitag D et al; Chemosphere 14: 1589-1616 (1985) (7) Dore M et al; Trib Cebedeau 28: 3-11 (1975) (8) Gellman I, Heukelekian H; Sew Indust Wastes 27: 793-801 (1955) (9) Gerhold RM, Malaney GW; J Water Pollut Control Fed 38: 562-79 (1966)]

**PEER REVIEWED**

ATMOSPHERIC FATE: According to a model of gas/particle partitioning of semivolatile organic compounds in the atmosphere(1), methanol, which has a vapor pressure of 127 mm Hg at 25 deg C(2), is expected to exist solely as a vapor in the ambient atmosphere. Vapor-phase methanol is degraded in the atmosphere by reaction with photochemically-produced hydroxyl radicals(SRC); the half-life for this reaction in air is estimated to be 17 days(SRC), calculated from its rate constant of 9.4X10-13 cu cm/molecule-sec at 25 deg C(3). [(1) Bidleman TF; Environ Sci Technol 22: 361-367 (1988) (2) Boublik T et al, eds; The Vapour Pressures of Pure Substances. 2nd rev ed. Amsterdam: Elsevier (1984) (3) Kwok ESC, Atkinson R; Estimation of hydroxyl radical reaction rate constants for gas-phase organic compounds using a structure-reactivity relationship: an update. Riverside, CA: Univ CA, Statewide Air Pollut Res CTR., CMA Contract No. AFC-8.0-OR-8.0-OR (1994)] **PEER REVIEWED**

ENVIRONMENTAL BIODEGRADATION: AEROBIC: The half-life for methanol applied to a sandy loam from Mississippi (68% sand, 23.4% silt, 8.6% clay, 0.94% organic carbon, pH 4.8) was 3.2 days(1). The half-life of methanol applied to a sandy silt loam from Texas (61.5% sand, 31.1% silt, 7.4% clay, 3.28% organic carbon, pH 7.8) was 1 day(1). The moisture content of each soil was maintained at approximately 80% of its field capacity over the 64 day incubation period, and the half-lives did not account for any potential volatilization loss. [(1) Loehr RC; Treatability potential for EPA listed hazardous wastes in soil. USEPA. Robert S. Kerr Environ. Res. Lab., ADA, OK. EPA/600/2-89/011 (1989)] **PEER REVIEWED**

AEROBIC: Methanol, present at 0.050 mg/L, reached 48% of its theoretical BOD in 5 days using a sewage inoculum(1). Using activated sludge as inoculum, methanol achieved 93%(2) and 21%(3) of its theoretical BOD in 2 day and 1 day Warburg respirometer studies, respectively. Using a standard dilution technique, methanol reached 53.4% of its theoretical BOD in 5 days, and 97.7% of the theoretical BOD was achieved in 50 days using sewage seed(4). Using an activated sludge acclimated to methanol, 55% of the theoretical BOD was achieved in 23 hours(5). Methanol had a half-life of 0.4 days in a sewage die-away test(6). [(1) Dore M et al; Trib Cebedeau 28: 3-11 (1975) (2) Gellman I, Heukelekian H; Sew Indust Wastes 27: 793-801 (1955) (3) Gerhold RM, Malaney GW; J Water Pollut Control Fed 38: 562-79 (1966) (4) Lamb CB, Jenkins GF; Proc 8th Industrial Waste Conf,. Purdue Univ p. 326-9 (1952) (5) McKinney RE, Jeris JS; Sew Indust Wastes 27: 728-35 (1955) (6) Wagner R; Vom Wasser 42: 271-305 (1974)] **PEER

REVIEWED**

AEROBIC: Using a starting concentration of 2.56 ppm, methanol achieved 88.7% of its theoretical BOD over a 5 day incubation period using a freshwater standard dilution technique, and 70.7% of its theoretical BOD over a 5 day incubation period using a sea water dilution technique(1). Significant biodegradation of organic waste (methanol and acetic acid and formic acid) was observed when injected into wells (850-1000 ft depth) as determined by concentration monitoring and microbial population count(2). Soil-sediment suspensions, maintainted under aerobic conditions, resulted in a 5-day CO2 evolution (14-C) of 53.4%(3). [(1) Takemoto S et al; Suishitsu Odaku Kenkyu 4: 80-90 (1981) (2) Ditommaso A, Elkan GH; Underground Waste Manage Artif Recharge, Prepr Pap Int Symp, 2nd 1: 585-99 (1973) (3) Scheunert I et al; Chemosphere 16: 1031-41 (1987)] **PEER

REVIEWED**

ANAEROBIC: Approximately 83-91% biodegradation was observed in an anaerobic die-away test, using marine water and sediment from the San Francisco Bay during a 3-day incubation period(1). Methanol was found to be susceptible to biodegradation in low oxygen subsurface regions in microcosm studies simulating subsurface conditions; complete degradation was observed within one year or less(2). Methanol degraded readily in test tube microcosms simulating subsurface soils and groundwaters from sites in VA and NY(3). Soil-sediment suspensions, maintained under anaerobic conditions, resulted in a 5-day CO2 evolution (14-C) of 46.3%(4). [(1) Oremland RL et al; Nature 296: 143-5 (1982) (2) Novak JT et al; Wat Sci Tech 17: 71-85 (1985) (3) Goldsmith CD; Diss Abstr Int B 46: 3767 (1985) (4) Scheunert I et al; Chemosphere 16: 1031-41 (1987)] **PEER REVIEWED**

ENVIRONMENTAL ABIOTIC DEGRADATION: The rate constant for the vapor-phase reaction of methanol with photochemically-produced hydroxyl radicals has been measured as 9.4X10-13 cu cm/molecule-sec at 25 deg C(1). This corresponds to an atmospheric half-life of about 17 days at an atmospheric concentration of 5X10+5 hydroxyl radicals per cu cm(1). Methanol is not expected to undergo hydrolysis in the environment due to the lack of hydrolyzable functional groups nor to directly photolyze due to the lack of absorption in the environmental UV spectrum ( > 290 nm)(2). [(1) Kwok ESC, Atkinson R; Estimation of hydroxyl radical reaction rate constants for gas-phase organic compounds using a structure-reactivity relationship: an update. Riverside, CA: Univ CA, Statewide Air Pollut Res CTR., CMA Contract NO. AFC-8.0-OR-8.0-OR (1994) (2) Lyman WJ et al; Handbook of Chemical Property 

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2/24/2011 htt p ://toxnet.nlm.nih. g ov/c g i- b in/sis/download.txtEstimation Methods. Washington, DC: Amer Chem Soc pp. 7-4, 7-5 (1990)]

**PEER REVIEWED**

The rate constant for the reaction of methanol with hydroxyl radicals in aqueous solution is approximately 1X10+9 l/mol-sec(1); if the hydroxyl radical concn of sunlit natural water is assumed to be 1X10-17 moles/l(2), the half-life would be approximately 2.2 years(SRC). Methanol in aqueous solution exhibited no degradation when exposed to sunlight using an EPA test protocol(3). Sediment and clay suspensions solution did not photocatalyze the degradation of methanol in aqueous solution during irradiation with UV light(4). Alcohols are generally resistant to environmental aqueous hydrolysis(5). [(1) Guesten H et al; Atmos Environ 15: 1763-5 (1981) (2) Mill T et al; Science 207: 886-7 (1980) (3) Hustert K et al; Chemosphere 10: 995-8 (1981) (4) Oliver BG et al; Environ Sci Technol 13: 1075-7 (1979) (5) Lyman WJ et al; Handbook of Chemical Property Estimation Methods NY: McGraw-Hill p. 7-4 (1982)] **PEER

REVIEWED**

ENVIRONMENTAL BIOCONCENTRATION: Fish (golden ide) exposed to 0.05 mg/L of methanol for three days in an aquatic tank had measured BCF values of less than 10(1). Based on a classification scheme(2), this BCF value suggests that bioconcentration in aquatic organisms is low(SRC). [(1) Freitag D et al; Chemosphere 14: 1589-1616 (1985) (2) Franke C et al; Chemosphere 29: 1501-14 (1994)]

**PEER REVIEWED**

SOIL ADSORPTION/MOBILITY: Using a structure estimation method based on molecular connectivity indices(1), the Koc for methanol can be estimated to be 1(SRC). According to a classification scheme(2), this estimated Koc value suggests that methanol is expected to have very high mobility in soil(SRC). [(1) Meylan WM et al; Environ Sci Technol 26: 1560-67 (1992) (2) Swann RL et al; Res Rev 85: 17-28 (1983)] **PEER REVIEWED**

VOLATILIZATION FROM WATER/SOIL: The Henry's Law constant for methanol is 4.55X10-6 atm-cu m/mole(SRC)(1). This Henry's Law constant indicates that methanol is expected to volatilize from water surfaces(2). Based on this Henry's Law constant, the volatilization half-life from a model river (1 m deep, flowing 1 m/sec, wind velocity of 3 m/sec)(2) is estimated as 3 days(SRC). The volatilization half-life from a model lake (1 m deep, flowing 0.05 m/sec, wind velocity of 0.5 m/sec)(2) is estimated as 35 days(SRC). Methanol's Henry's Law constant indicates that volatilization from moist soil surfaces may occur(SRC). The potential for volatilization of methanol from dry soil surfaces may exist(SRC) based upon a vapor pressure of 127 mm Hg(3). [(1) Gaffney JS et al; Environ Sci Technol 21: 519-23 (1987) (2) Lyman WJ et al; Handbook of Chemical Property Estimation Methods. Washington, DC: Amer Chem Soc pp. 15-1 to 15-29 (1990) (3) Boublik T et al, eds; The Vapour Pressures of Pure Substances. 2nd rev ed. Amsterdam: Elsevier (1984)] **PEER REVIEWED**

ENVIRONMENTAL WATER CONCENTRATIONS: DRINKING WATER: Methanol has been qualitatively detected in drinking water from Miami, FL, Seattle, WA, Philadelphia, PA, Cincinnati, OH, and New Orleans, LA(1,2). As part of the USEPA National Organics Reconnaissance Survey (NORS), methanol was detected in 6 of 10 drinking waters from USA cities(3). [(1) USEPA; Preliminary Assessment of Suspected Carcinogens in Water. Interim Report to Congress, June, 1975. Washington DC (1975) (2) USEPA; New Orleans Area Water Supply Draft Analytical Report by the Lower Mississippi River Facility, Sliddell, LA. Dallas, TX (1974) (3) Bedding ND et al; Sci Total Environ 25: 143-67 (1982)] **PEER REVIEWED**

RAIN WATER: Methanol was detected at a mean level of 22 ppb in thunderstorm water collected from Santa Rita, AZ in Sept, 1982(1). [(1) Snider JR, Dawson GA; J Geophys Res, D2, 90: 3797-805 (1985)] **PEER

REVIEWED**

EFFLUENT CONCENTRATIONS: Methanol levels of 18-70 ppm were detected in wastewater effluents from a chemical mfg facility (near the Brackish River), but none was detected in associated river water or sediments(1). Methanol has been identified in wastewater effluents from chemical, paper, and latex manufacturing plants and from sewage treatment plants(2). Concn of 42.4 ppm detected in leachate from the Love Canal in Niagara Falls, NY(3). Concn of 1050 ppm detected in condensate waters from a coal-gasification plant(4). Levels of 0.1-0.6 ppm were found in exhausts from engines using simple hydrocarbon fuels(5). Methanol has been identified in exhausts from both gasoline and diesel engines(6). [(1) Jungclaus GA et al; Environ Sci Technol 12: 88-96 (1978) (2) Shackelford WM, Keith LH; Frequency of Organic Compounds Identified in Water EPA-600/4-76- 062 p. 169 (1976) (3) Venkataramani ES et al; CRC Crit Rev Environ Control 14: 333-76 (1984) (4) Mohr DH, King J; Environ Sci Technol 19: 929-35 (1985) (5) Seizinger DE, Dimitriades B; J Air Pollut Control Assoc 22: 47-51 (1972) (6) Jonsson A et al; Environ International 11: 383-92 (1985)] **PEER REVIEWED**

ATMOSPHERIC CONCENTRATIONS: URBAN/SUBURBAN: Avg ambient concns of methanol in the range of 3.83-26.7 ppb were detected at 5 sites in and around Stockholm, Sweden(1). Methanol was detected at levels of 0.10 to 2.21 ng/cu m in urban atmospheric particulates in Kobe City, Japan in 1999(2). [(1) Jonsson A et al; Environ International 11: 383-92 (1985) (2) Suzuki Y et al; Environ Sci Technol 

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2/24/2011 htt p ://toxnet.nlm.nih. g ov/c g i- b in/sis/download.txt35: 2656-64 (2001)] **PEER REVIEWED**

INDOOR: Methanol has been detected (concn not reported) in indoor air of residential and office buildings(1,2). [(1) Jarke FH et al; ASHRAE Trans 87: 153-66 (1981) (2) Tsuchiya Y; Volatile Organic Compounds in Indoor Air. Am Chem Soc Div Environ Chem Preprint, New Orleans, LA 27: 183-5 (1987)] **PEER REVIEWED**

RURAL/REMOTE: Methanol was detected at mean ambient atmospheric concns of 7.9 and 2.6 ppb at two remote AZ locations during 1982 monitoring(1). Concns of 0.0-1.2 ppb (ave 0.77 ppb methanol and ethanol) were identified in Arctic air from Point Barrows, Alaska in Sept 1967(2). Methanol was detected in the atmosphere above the Arapaho National Forest in Colorado at levels of approximately 2-12 ppb in July and August 1999(3). [(1) Snider JR, Dawson GA; J Geophys Res, D2, 90: 3797-805 (1985) (2) Cavanagh LA et al; Environ Sci Technol 3: 251-7 (1969) (3) Baker B et al; Environ Sci Technol 35: 1701-9 (2001)] **PEER REVIEWED**

FOOD SURVEY VALUES: Methanol has been identified as a volatile component of dried legumes (concn 1.5-7.9 ppm), baked potatoes, and roasted filbert nuts(1-3). Methanol was identified, not quantified, in the volatile flavor components of fresh grapefruit(4). Methanol was detected at levels of 7-126 ppm in fresh squeezed orange juice(5). [(1) Coleman EC et al; J Agric Food Chem 29: 42-8 (1981) (2) Kinlin TE et al; J Agric Food Chem 20: 1021-8 (1972) (3) Lovegren NV et al; J Agric Food Chem 27: 851-3 (1979) (4) Cadwallader KR, Xu Y; J Agric Food Chem 42: 782-4 (1994) (5) Moshonas NG, Shaw PE; J Agric Food Chem 42: 1525-8 (1994)] **PEER REVIEWED**

PLANT CONCENTRATIONS: Methanol has been identified as a volatile emission product from evergreen cypress trees(1) and alfalfa(2). [(1) Isidorov VA et al; Atmos Environ 19: 1-8 (1985) (2) Owens LD et al; Phytopathology 59: 1468-72 (1969)] **PEER

REVIEWED**

OTHER ENVIRONMENTAL CONCENTRATIONS: Methanol was identified as a component of several industrial paint strippers(1). Engine exhausts from both gasoline and diesel vehicles have been found to contain methanol(2). Methanol has been identified as a constituent of tobacco smoke(3). [(1) Hahn WJ, Werschulz PO; Evaluation of Alternatives to Toxic Organic Paint Strippers. USEPA-600/S2-86-063 (1986) (2) Jonsson A et al; Environ International 11: 383-92 (1985) (3) Graedel TE et al; Atmospheric Chemical Compounds. Sources, Occurrence, and Bioassay. Orlando, FL: Academic Press p. 232 (1986)] **PEER REVIEWED**

ENVIRONMENTAL STANDARDS & REGULATIONS:

FIFRA REQUIREMENTS: Residues of methanol are exempted from the requirement of a tolerance when used as a solvent in accordance with good agricultural practice as inert (or occasionally active) ingredients in pesticide formulations applied to growing crops or to raw agricultural commodities after harvest. [40 CFR

180.910; U.S. National Archives and Records Administration's Electronic Code of Federal Regulations. Available from, as of June 1, 2005: http://www.gpoaccess.gov/ecfr] **PEER REVIEWED**

Residues of methanol are exempted from the requirement of a tolerance when used as a synergist in accordance with good agricultural practice as inert (or occasionally active) ingredients in pesticide formulations applied to growing crops only. [40 CFR 180.920; U.S. National Archives and Records Administration's Electronic Code of Federal Regulations. Available from, as of June 1, 2005: http://www.gpoaccess.gov/ecfr] **PEER REVIEWED**

Residues of methanol are exempted from the requirement of a tolerance when used as a solvent, cosolvent in accordance with good agricultural practice as inert (or occasionally active) ingredients in pesticide formulations applied to animals. [40 CFR 180.930; U.S. National Archives and Records Administration's Electronic Code of Federal Regulations. Available from, as of June 1, 2005: http://www.gpoaccess.gov/ecfr] **PEER REVIEWED**

As the federal pesticide law FIFRA directs, EPA is conducting a comprehensive review of older pesticides to consider their health and

environmental effects and make decisions about their future use. Under this pesticide reregistration program, EPA examines health and safety data for pesticide active ingredients initially registered before November 1, 1984, and determines whether they are eligible for reregistration. In addition, all pesticides must meet the new safety standard of the Food Quality Protection Act of 1996. Pesticides for which EPA had not issued Registration Standards prior to the effective date of FIFRA '88 were divided into three lists based upon their potential for human exposure and other factors, with List B containing pesticides of greater concern and List D pesticides of less concern. Methyl alcohol is found on List D. Case No: 4003; Pesticide type: insecticide, fungicide, herbicide, antimicrobial; Case Status: RED Approved 3/95; OPP has made a decision that some/all uses of the pesticide are eligible for reregistration, as reflected in a Reregistration Eligibility Decision (RED) document .; Active ingredient (AI): methyl alcohol; AI Status: The active ingredient is no longer contained in any registered products. Thus, we characterize it as "cancelled." [United States Environmental Protection Agency/ 

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2/24/2011 htt p ://toxnet.nlm.nih. g ov/c g i- b in/sis/download.txtPrevention, Pesticides and Toxic Substances; Status of Pesticides in Registration, Reregistration, and Special Review. (1998) EPA 738-R-98-002, p. 290] **PEER REVIEWED**

CERCLA REPORTABLE QUANTITIES: Persons in charge of vessels or facilities are required to notify the National Response Center (NRC) immediately, when there is a release of this designated hazardous substance, in an amount equal to or greater than its reportable quantity of 5000 lb or 2270 kg. The toll free number of the NRC is (800) 424-8802. The rule for determining when notification is required is stated in 40 CFR 302.4 (section IV. D.3.b). [40 CFR

302.4; U.S. National Archives and Records Administration's Electronic Code of Federal Regulations. Available from, as of June 1, 2005: http://www.gpoaccess.gov/ecfr] **PEER REVIEWED**

RCRA REQUIREMENTS: U154; As stipulated in 40 CFR 261.33, when methanol, as a commercial chemical product or manufacturing chemical intermediate or an off-specification commercial chemical product or a manufacturing chemical intermediate, becomes a waste, it must be managed according to Federal and/or State hazardous waste regulations. Also defined as a hazardous waste is any residue, contaminated soil, water, or other debris resulting from the cleanup of a spill, into water or on dry land, of this waste. Generators of small quantities of this waste may qualify for partial exclusion from hazardous waste regulations (40 CFR 261.5). [40 CFR 261.33;

U.S. National Archives and Records Administration's Electronic Code of Federal Regulations. Available from, as of June 1, 2005: http://www.gpoaccess.gov/ecfr] **PEER REVIEWED**

F003; When methanol is a spent solvent, it is classified as a hazardous waste from a nonspecific source (F003), as stated in 40 CFR 261.31, and must be managed according to State and/or Federal hazardous waste regulations. [40 CFR 261.31; U.S. National Archives and Records Administration's Electronic Code of Federal Regulations. Available from, as of June 1, 2005: http://www.gpoaccess.gov/ecfr] **PEER REVIEWED**

ATMOSPHERIC STANDARDS: This action promulgates standards of performance for equipment leaks of Volatile Organic Compounds (VOC) in the Synthetic Organic Chemical Manufacturing Industry (SOCMI). The intended effect of these standards is to require all newly constructed, modified, and reconstructed SOCMI process units to use the best demonstrated system of continuous emission reduction for equipment leaks of VOC, considering costs, non air quality health and environmental impact and energy requirements. Methanol is produced, as an intermediate or a final product, by process units covered under this subpart. [40 CFR 60.489; U.S. National Archives and Records Administration's Electronic Code of Federal Regulations. Available from, as of June 1, 2005: http://www.gpoaccess.gov/ecfr] **PEER REVIEWED**

Listed as a hazardous air pollutant (HAP) generally known or suspected to cause serious health problems. The Clean Air Act, as amended in 1990, directs EPA to set standards requiring major sources to sharply reduce routine emissions of toxic pollutants. EPA is required to establish and phase in specific performance based standards for all air emission sources that emit one or more of the listed pollutants. Methanol is included on this list. [Clean Air Act as amended in 1990, Sect. 112 (b) (1) Public Law 101-549 Nov. 15, 1990] **PEER REVIEWED**

STATE DRINKING WATER GUIDELINES: (FL) FLORIDA 5,000 ug/L [USEPA/Office of Water; Federal-State Toxicology and Risk Analysis Committee (FSTRAC). Summary of State and Federal Drinking Water Standards and Guidelines (11/93) To Present] **PEER

REVIEWED**

(MN) MINNESOTA 3000 ug/L [USEPA/Office of Water; Federal-State Toxicology and Risk Analysis Committee (FSTRAC). Summary of State and Federal Drinking Water Standards and Guidelines (11/93) To Present] **PEER

REVIEWED**

(NH) NEW HAMPSHIRE 4,000 ug/L [USEPA/Office of Water; Federal-State Toxicology and Risk Analysis Committee (FSTRAC). Summary of State and Federal Drinking Water Standards and Guidelines (11/93) To Present] **QC REVIEWED**

(WI) WISCONSIN 5000 ug/L [USEPA/Office of Water; Federal-State Toxicology and Risk Analysis Committee (FSTRAC). Summary of State and Federal Drinking Water Standards and Guidelines (11/93) To Present] **PEER

REVIEWED**

FDA REQUIREMENTS: Methyl alcohol is an indirect food additive for use only as a component of adhesives. [21 CFR 175.105; U.S. National Archives and Records Administration's Electronic Code of Federal Regulations. Available from, as of June 1, 2005: http://www.gpoaccess.gov/ecfr] **PEER REVIEWED**

Methyl alcohol may be present in the following foods under the conditions specified: (a) In spice oleoresins as a residue from the extraction of spice, at a level not to exceed 50 parts per million. (b) In hops extract as a residue from the extraction of hops, at a level not to exceed 2.2 percent by weight; Provided, that: (1) The hops extract is added to the wort before or during cooking in the manufacture of beer. (2) The label 

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2/24/2011 htt p ://toxnet.nlm.nih. g ov/c g i- b in/sis/download.txtof the hops extract specifies the presence of methyl alcohol and provides for the use of the hops extract only as prescribed by paragraph (b)(1) of this section. [21 CFR 173.250; U.S. National Archives and Records Administration's Electronic Code of Federal Regulations. Available from, as of June 1, 2005: http://www.gpoaccess.gov/ecfr] **PEER REVIEWED**

ALLOWABLE TOLERANCES: Residues of methanol are exempted from the requirement of a tolerance when used as a solvent in accordance with good agricultural practice as inert (or occasionally active) ingredients in pesticide formulations applied to growing crops or to raw agricultural commodities after harvest. [40 CFR

180.910; U.S. National Archives and Records Administration's Electronic Code of Federal Regulations. Available from, as of June 1, 2005: http://www.gpoaccess.gov/ecfr] **PEER REVIEWED**

Residues of methanol are exempted from the requirement of a tolerance when used as a synergist in accordance with good agricultural practice as inert (or occasionally active) ingredients in pesticide formulations applied to growing crops only. [40 CFR 180.920; U.S. National Archives and Records Administration's Electronic Code of Federal Regulations. Available from, as of June 1, 2005: http://www.gpoaccess.gov/ecfr] **PEER REVIEWED**

Residues of methanol are exempted from the requirement of a tolerance when used as a solvent, cosolvent in accordance with good agricultural practice as inert (or occasionally active) ingredients in pesticide formulations applied to animals. [40 CFR 180.930; U.S. National Archives and Records Administration's Electronic Code of Federal Regulations. Available from, as of June 1, 2005: http://www.gpoaccess.gov/ecfr] **PEER REVIEWED**

CHEMICAL/PHYSICAL PROPERTIES:

MOLECULAR FORMULA: C-H4-O [Lewis, R.J. Sax's Dangerous Properties of Industrial Materials. 9th ed. Volumes 1-3. New York, NY: Van Nostrand Reinhold, 1996., p. 2174]

**PEER REVIEWED**

MOLECULAR WEIGHT: 32.04 [O'Neil, M.J. (ed.). The Merck Index - An Encyclopedia of Chemicals, Drugs, and Biologicals. 13th Edition, Whitehouse Station, NJ: Merck and Co., Inc., 2001., p. 1065] **PEER REVIEWED**

COLOR/FORM: Colorless liquid [NIOSH. NIOSH Pocket Guide to Chemical Hazards & Other Databases CD-ROM. Department of Health & Human Services, Centers for Disease Prevention & Control. National Institute for Occupational Safety& Health. DHHS (NIOSH) Publication No. 2004-103 (2003).] **PEER

REVIEWED**

ODOR: Alcoholic odor; pungent odor when crude [O'Neil, M.J. (ed.). The Merck Index - An Encyclopedia of Chemicals, Drugs, and Biologicals. 13th Edition, Whitehouse Station, NJ: Merck and Co., Inc., 2001., p. 1065]

**PEER REVIEWED**

Characteristic pungent odor [NIOSH. NIOSH Pocket Guide to Chemical Hazards & Other Databases CD-ROM. Department of Health & Human Services, Centers for Disease Prevention & Control. National Institute for Occupational Safety& Health. DHHS (NIOSH) Publication No. 2004-103 (2003).] **PEER REVIEWED**

BOILING POINT: 64.7 deg C at 760 mm Hg [O'Neil, M.J. (ed.). The Merck Index - An Encyclopedia of Chemicals, Drugs, and Biologicals. 13th Edition, Whitehouse Station, NJ: Merck and Co., Inc., 2001., p. 1065] **PEER

REVIEWED**

MELTING POINT: -97.8 deg C [O'Neil, M.J. (ed.). The Merck Index - An Encyclopedia of Chemicals, Drugs, and Biologicals. 13th Edition, Whitehouse Station, NJ: Merck and Co., Inc., 2001., p. 1065] **PEER REVIEWED**

CRITICAL TEMPERATURE & PRESSURE: Critical temperature: 240.0 deg C; critical pressure: 78.5 atm [O'Neil, M.J. (ed.). The Merck Index - An Encyclopedia of Chemicals, Drugs, and Biologicals. 13th Edition, Whitehouse Station, NJ: Merck and Co., Inc., 2001., p. 1065] **PEER REVIEWED**

DENSITY/SPECIFIC GRAVITY: 0.8100 at 0 deg C/4 deg C; 0.7866 at 25 deg C/4 deg C [O'Neil, M.J. (ed.). The Merck Index - An Encyclopedia of Chemicals, Drugs, and Biologicals. 13th Edition, Whitehouse Station, NJ: Merck and Co., Inc., 2001., p. 1065] **PEER REVIEWED**

DISSOCIATION CONSTANTS: pKa = 15.3 [Serjeant, E.P., Dempsey B.; Ionisation Constants of Organic Acids in Aqueous Solution. International Union of Pure and Applied Chemistry (IUPAC). IUPAC Chemical Data Series No. 23, 1979. New York, New York: Pergamon Press, Inc., p. 989] **PEER REVIEWED** 

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2/24/2011 htt p ://toxnet.nlm.nih. g ov/c g i- b in/sis/download.txtHEAT OF COMBUSTION: 723 kJ/mole [Environment Canada; Tech Info for Problem Spills: Methanol (Draft) p.4 (1981)] **PEER REVIEWED**

HEAT OF VAPORIZATION: 39.2 kJ/mole [Environment Canada; Tech Info for Problem Spills: Methanol (Draft) p.4 (1981)] **PEER REVIEWED**

OCTANOL/WATER PARTITION COEFFICIENT: log Kow= -0.77 [Hansch, C., Leo, A., D. Hoekman. Exploring QSAR - Hydrophobic, Electronic, and Steric Constants. Washington, DC: American Chemical Society., 1995., p. 3] **PEER REVIEWED**

SOLUBILITIES: Miscible with ethanol, ether, benzene, most organic solvents and ketones. [O'Neil, M.J. (ed.). The Merck Index - An Encyclopedia of Chemicals, Drugs, and Biologicals. 13th Edition, Whitehouse Station, NJ: Merck and Co., Inc., 2001., p. 1065] **PEER REVIEWED**

Sol in acetone, chloroform [Lide, D.R., G.W.A. Milne (eds.). Handbook of Data on Organic Compounds. Volume I. 3rd ed. CRC Press, Inc. Boca Raton ,FL. 1994., p. V4: 3388] **PEER REVIEWED**

Completely miscible in water @ 20 deg C [Flick, E.W. Industrial Solvents Handbook. 3rd ed. Park Ridge, NJ: Noyes Publications, 1985., p. 188]

**PEER REVIEWED**

Water solubility = miscible [Riddick, J.A., W.B. Bunger, Sakano T.K. Techniques of Chemistry 4th ed., Volume II. Organic Solvents. New York, NY: John Wiley and Sons., 1985., p. 190] **PEER REVIEWED**

SPECTRAL PROPERTIES: Index of refraction: 1.3292 at 20 deg C/D [O'Neil, M.J. (ed.). The Merck Index - An Encyclopedia of Chemicals, Drugs, and Biologicals. 13th Edition, Whitehouse Station, NJ: Merck and Co., Inc., 2001., p. 1065]

**PEER REVIEWED**

MAX ABSORPTION (GAS): 183.3 NM (LOG EPSILON= 2.18) [Weast, R.C. (ed.). Handbook of Chemistry and Physics. 52nd ed. Cleveland: The Chemical Rubber Co., 1972., p. C-370] **PEER REVIEWED**

IR: 287 (Sadtler Research Laboratories IR Grating Collection) [Lide, D.R., G.W.A. Milne (eds.). Handbook of Data on Organic Compounds. Volume I. 3rd ed. CRC Press, Inc. Boca Raton ,FL. 1994., p. V4: 3388] **PEER REVIEWED**

UV: 1-3 (Organic Electronic Spectral Data, Phillips et al, John Wiley & Sons, New York) [Lide, D.R., G.W.A. Milne (eds.). Handbook of Data on Organic Compounds. Volume I. 3rd ed. CRC Press, Inc. Boca Raton ,FL. 1994., p. V4: 3388] **PEER REVIEWED**

NMR: 1 (Varian Associates NMR Spectra Catalogue) [Lide, D.R., G.W.A. Milne (eds.). Handbook of Data on Organic Compounds. Volume I. 3rd ed. CRC Press, Inc. Boca Raton ,FL. 1994., p. V4: 3388] **PEER REVIEWED**

MASS: 61305 (NIST/EPA/MSDC Mass Spectral Database, 1990 version) [Lide, D.R., G.W.A. Milne (eds.). Handbook of Data on Organic Compounds. Volume I. 3rd ed. CRC Press, Inc. Boca Raton ,FL. 1994., p. V4: 3388] **PEER

REVIEWED**

SURFACE TENSION: 22.61 mN/m (at 20 deg C) [Environment Canada; Tech Info for Problem Spills: Methanol (Draft) p.4 (1981)] **PEER REVIEWED**

VAPOR DENSITY: 1.11 [Environment Canada; Tech Info for Problem Spills: Methanol (Draft) p.3 (1981)] **PEER REVIEWED**

VAPOR PRESSURE: 127 mm Hg at 25 deg C [Boublik, T., Fried, V., and Hala, E., The Vapour Pressures of Pure Substances. Second Revised Edition. Amsterdam: Elsevier, 1984.] **PEER REVIEWED**

VISCOSITY: 0.614 mPa sec [Environment Canada; Tech Info for Problem Spills: Methanol (Draft) p.4 (1981)] **PEER REVIEWED**

OTHER CHEMICAL/PHYSICAL PROPERTIES: Dipole moment: 1.69 /debyes/; specific heat: 0.595-0.605 at 20-25 deg C, forms Azeotropes with many cmpd; burns with nonluminous bluish flame ... [O'Neil, M.J. (ed.). The Merck Index - An Encyclopedia of Chemicals, Drugs, and Biologicals. 13th Edition, Whitehouse Station, NJ: Merck and Co., Inc., 2001., p. 1065] **PEER REVIEWED**

1 MG/L= 764 PPM; 1 PPM= 1.31 MG/CU M @ 25 DEG C, 760 MM HG [Clayton, G. D. and F. E. Clayton (eds.). Patty's Industrial Hygiene and Toxicology: Volume 2A, 2B, 2C: Toxicology. 3rd ed. New York: John Wiley Sons, 1981-1982., p. 4530] **PEER REVIEWED**

Heat of fusion: 103 J/g [Kirk-Othmer Encyclopedia of Chemical Technology. 4th ed. Volumes 1: New York, NY. John Wiley and Sons, 1991-Present., p. V16: 538 (1995)] **PEER REVIEWED** 

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2/24/2011 htt p ://toxnet.nlm.nih. g ov/c g i- b in/sis/download.txtPartition coefficients at 37 deg C for methanol into blood= 2,100; into oil= 56. [Sato A, Nakajima T; Scand J Work Environ Health 13: 81-93 (1987)] **PEER REVIEWED** <a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=3299685" target=new>PubMed Abstract

Vapor pressure= 100 mm Hg at 21.2 deg C [Lewis, R.J. Sax's Dangerous Properties of Industrial Materials. 9th ed. Volumes 1-3. New York, NY: Van Nostrand Reinhold, 1996., p. 2174] **PEER REVIEWED**

Henry's Law constant = 4.55X10-6 atm-cu m/mol at 25 deg C [Gaffney JS et al; Environ Sci Technol 21: 519-23 (1987)] **PEER REVIEWED** <a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=19994967" target=new>PubMed Abstract

Hydroxyl radical reaction rate constant = 9.4X10-13 cu cm/molec-sec at 25 deg C [Kwok ESC, Atkinson R; Estimation of hydroxyl radical reaction rate constants for gas-phase organic compounds using a structure-reactivity relationship: an update. Riverside, CA: Univ CA, Statewide Air Pollut Res CTR., CMA Contract NO. AFC-8.0-OR-8.0-OR (1994)] **PEER REVIEWED**

CHEMICAL SAFETY & HANDLING:

DOT EMERGENCY GUIDELINES: /GUIDE 131: FLAMMABLE LIQUIDS-TOXIC/ Health: TOXIC; may be fatal if inhaled, ingested or absorbed through skin. Inhalation or contact with some of these materials will irritate or burn skin and eyes. Fire will produce irritating, corrosive and/or toxic gases. Vapors may cause dizziness or suffocation. Runoff from fire control or dilution water may cause pollution. [U.S. Department of Transportation. 2004 Emergency Response Guidebook. A Guide book for First Responders During the Initial Phase of a Dangerous Goods/Hazardous Materials Incident. Washington, D.C. 2004] **QC REVIEWED**

/GUIDE 131: FLAMMABLE LIQUIDS-TOXIC/ Fire or Explosion: HIGHLY FLAMMABLE: Will be easily ignited by heat, sparks or flames. Vapors may form explosive mixtures with air. Vapors may travel to source of ignition and flash back. Most vapors are heavier than air. They will spread along ground and collect in low or confined areas (sewers, basements, tanks). Vapor explosion and poison hazard indoors, outdoors or in sewers. Those substances designated with a "P" may polymerize explosively when heated or involved in a fire. Runoff to sewer may create fire or explosion hazard. Containers may explode when heated. Many liquids are lighter than water. [U.S. Department of Transportation. 2004 Emergency Response Guidebook. A Guide book for First Responders During the Initial Phase of a Dangerous Goods/Hazardous Materials Incident. Washington, D.C. 2004] **QC REVIEWED**

/GUIDE 131: FLAMMABLE LIQUIDS-TOXIC/ Public Safety: CALL Emergency Response Telephone Number ... . As an immediate precautionary measure, isolate spill or leak area for at least 50 meters (150 feet) in all directions. Keep unauthorized personnel away. Stay upwind. Keep out of low areas. Ventilate closed spaces before entering. [U.S. Department of Transportation. 2004 Emergency Response Guidebook. A Guide book for First Responders During the Initial Phase of a Dangerous Goods/Hazardous Materials Incident. Washington, D.C. 2004] **QC REVIEWED**

/GUIDE 131: FLAMMABLE LIQUIDS-TOXIC/ Protective Clothing: Wear positive pressure self-contained breathing apparatus (SCBA). Wear chemical protective clothing that is specifically recommended by the manufacturer. It may provide little or no thermal protection. Structural firefighters' protective clothing provides limited protection in fire situations ONLY; it is not effective in spill situations where direct contact with the substance is possible. [U.S. Department of Transportation. 2004 Emergency Response Guidebook. A Guide book for First Responders During the Initial Phase of a Dangerous Goods/Hazardous Materials Incident. Washington, D.C. 2004] **QC REVIEWED**

/GUIDE 131: FLAMMABLE LIQUIDS-TOXIC/ Evacuation: ... Fire: If tank, rail car or tank truck is involved in a fire, ISOLATE for 800 meters (1/2 mile) in all directions; also, consider initial evacuation for 800 meters (1/2 mile) in all directions. [U.S. Department of Transportation. 2004 Emergency Response Guidebook. A Guide book for First Responders During the Initial Phase of a Dangerous Goods/Hazardous Materials Incident. Washington, D.C. 2004] **QC REVIEWED**

/GUIDE 131: FLAMMABLE LIQUIDS-TOXIC/ Fire: CAUTION: All these products have a very low flash point. Use of water spray when fighting fire may be inefficient. Small fires: Dry chemical, CO2, water spray or alcohol-resistant foam. Large fires: Water spray, fog or alcohol-resistant foam. Move containers from fire area if you can do it without risk. Dike fire control water for later disposal; do not scatter the material. Use water spray or fog; do not use straight streams. Fire involving tanks or car/trailer loads: Fight fire from maximum distance or use unmanned hose holders or monitor nozzles. Cool containers with flooding quantities of water until well after fire is out. Withdraw immediately in case of rising sound from venting safety devices or discoloration of tank. ALWAYS stay away from tanks engulfed in fire. For massive fire use unmanned hose holders or monitor nozzles; if this is impossible, withdraw from area and 

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2/24/2011 htt p ://toxnet.nlm.nih. g ov/c g i- b in/sis/download.txtlet fire burn. [U.S. Department of Transportation. 2004 Emergency Response Guidebook. A Guide book for First Responders During the Initial Phase of a Dangerous Goods/Hazardous Materials Incident. Washington, D.C. 2004] **QC

REVIEWED**

/GUIDE 131: FLAMMABLE LIQUIDS-TOXIC/ Spill or Leak: Fully encapsulating, vapor protective clothing should be worn for spills and leaks with no fire. ELIMINATE all ignition sources (no smoking, flares, sparks or flames in immediate area). All equipment used when handling the product must be grounded. Do not touch or walk through spilled material. Stop leak if you can do it without risk. Prevent entry into waterways, sewers, basements or confined areas. A vapor suppressing foam may be used to reduce vapors. Small spills: Absorb with earth, sand or other non-combustible material and transfer to containers for later disposal. Use clean non-sparking tools to collect absorbed material. Large spills: Dike far ahead of liquid spill for later disposal. Water spray may reduce vapor; but may not prevent ignition in closed spaces. [U.S. Department of Transportation. 2004 Emergency Response Guidebook. A Guide book for First Responders During the Initial Phase of a Dangerous Goods/Hazardous Materials Incident. Washington, D.C. 2004] **QC REVIEWED**

/GUIDE 131: FLAMMABLE LIQUIDS-TOXIC/ First Aid: Move victim to fresh air. Call 911 or emergency medical service. Give artificial respiration if victim is not breathing. Do not use mouth-to-mouth method if victim ingested or inhaled the substance; give artificial respiration with the aid of a pocket mask equipped with a one-way valve or other proper respiratory medical device. Administer oxygen if breathing is difficult. Remove and isolate contaminated clothing and shoes. In case of contact with substance, immediately flush skin or eyes with running water for at least 20 minutes. Wash skin with soap and water. Keep victim warm and quiet. In case of burns, immediately cool affected skin for as long as possible with cold water. Do not remove clothing if adhering to skin. Effects of exposure (inhalation, ingestion or skin contact) to substance may be delayed. Ensure that medical personnel are aware of the material(s) involved and take precautions to protect themselves. [U.S. Department of Transportation. 2004 Emergency Response Guidebook. A Guide book for First Responders During the Initial Phase of a Dangerous Goods/Hazardous Materials Incident. Washington, D.C. 2004] **QC REVIEWED**

ODOR THRESHOLD: The air odor threshold for methanol has been reported as 100 ppm. A level of 2,000 ppm ... is barely detectable. [Bingham, E.; Cohrssen, B.; Powell, C.H.; Patty's Toxicology Volumes 1-9 5th ed. John Wiley & Sons. New York, N.Y. (2001)., p. V6 p.370] **PEER REVIEWED**

Low threshold= 13.1150 mg/cu m; High threshold= 26840 mg/cu m; Irritating concn= 22875 mg/cu m. [Ruth JH; Am Ind Hyg Assoc J 47: A-142-51 (1986)]

**PEER REVIEWED**

SKIN, EYE AND RESPIRATORY IRRITATIONS: /Methanol/ is an eye and skin irritant. [Lewis, R.J. Sax's Dangerous Properties of Industrial Materials. 9th ed. Volumes 1-3. New York, NY: Van Nostrand Reinhold, 1996., p. 2174] **PEER REVIEWED**

FIRE POTENTIAL: Dangerous fire hazard when exposed to heat, flame or oxidizers. [Lewis, R.J. Sax's Dangerous Properties of Industrial Materials. 9th ed. Volumes 1-3. New York, NY: Van Nostrand Reinhold, 1996., p. 2175] **PEER

REVIEWED**

NFPA HAZARD CLASSIFICATION: Health: 1. 1= Materials that, on exposure, would cause irritation, but only minor residual injury, including those requiring the use of an approved air-purifying respirator. These materials are only slightly hazardous to health and only breathing protection is needed. [Fire Protection Guide to Hazardous Materials. 13 ed. Quincy, MA: National Fire Protection Association, 2002., p. 325-81] **PEER REVIEWED**

Flammability: 3. 3= This degree includes Class IB and IC flammable liquids and materials that can be easily ignited under almost all normal temperature conditions. Water may be ineffective in controlling or extinguishing fires in such materials. [Fire Protection Guide to Hazardous Materials. 13 ed. Quincy, MA: National Fire Protection Association, 2002., p. 325-81] **PEER REVIEWED**

Reactivity: 0. 0= This degree includes materials that are normally stable, even under fire exposure conditions, and that do not react with water. Normal fire fighting procedures may be used. [Fire Protection Guide to Hazardous Materials. 13 ed. Quincy, MA: National Fire Protection Association, 2002., p. 325-81] **PEER REVIEWED**

FLAMMABLE LIMITS: Lower limits is 6.0%; Upper limits is 36% [Fire Protection Guide to Hazardous Materials. 13 ed. Quincy, MA: National Fire Protection Association, 2002., p. 325-81] **PEER REVIEWED**

FLASH POINT: 15.6 deg C (open cup) /from table/ [WHO; Environ Health Criteria 196: Methanol p.11 (1997). Available from, as of July 14, 2005: http://www.inchem.org/documents/ehc/ehc/ehc196.htm] **PEER REVIEWED** 

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2/24/2011 htt p ://toxnet.nlm.nih. g ov/c g i- b in/sis/download.txt54 deg F (12 deg C) (closed cup) [O'Neil, M.J. (ed.). The Merck Index - An Encyclopedia of Chemicals, Drugs, and Biologicals. 13th Edition, Whitehouse Station, NJ: Merck and Co., Inc., 2001., p. 1065] **PEER

REVIEWED**

AUTOIGNITION TEMPERATURE: 867 DEG F (464 DEG C) [Fire Protection Guide to Hazardous Materials. 13 ed. Quincy, MA: National Fire Protection Association, 2002., p. 325-81]

**PEER REVIEWED**

FIRE FIGHTING PROCEDURES: To fight fire use alcohol foam. [Lewis, R.J. Sax's Dangerous Properties of Industrial Materials. 9th ed. Volumes 1-3. New York, NY: Van Nostrand Reinhold, 1996., p. 2175] **PEER REVIEWED**

EXPLOSIVE LIMITS & POTENTIAL: Lower explosive limit 6.0%; Upper explosive limit 36.5 % [Lewis, R.J. Sax's Dangerous Properties of Industrial Materials. 9th ed. Volumes 1-3. New York, NY: Van Nostrand Reinhold, 1996., p. 2174] **PEER REVIEWED**

Explosive in the form of vapor when exposed to heat or flame. [Lewis, R.J. Sax's Dangerous Properties of Industrial Materials. 9th ed. Volumes 1-3. New York, NY: Van Nostrand Reinhold, 1996., p. 2175] **PEER

REVIEWED**

HAZARDOUS REACTIVITIES & INCOMPATIBILITIES: Distillation of mixtures with C1-C3 alcohols gives highly explosive alkyl perchlorates. /Barium perchlorate/ [Bretherick, L. Handbook of Reactive Chemical Hazards. 4th ed. Boston, MA: Butterworth-Heinemann Ltd., 1990, p. 80] **PEER REVIEWED**

During hydrogenation of an unspecified substrate in methanol solution under hydrogen at 100 bar with Raney nickel catalyst, sudden temperature increase led to hydrogenolysis of methanol to methane, and the pressure increase led to an overpressure accident. Such incidents may be avoided by control of agitation, limiting the amount of catalyst, and checking thermal stability of starting materials and end products beforehand. [Bretherick, L. Handbook of Reactive Chemical Hazards. 4th ed. Boston, MA: Butterworth-Heinemann Ltd., 1990, p. 174] **PEER REVIEWED**

Can react vigorously with oxidizing materials. [Lewis, R.J. Sax's Dangerous Properties of Industrial Materials. 9th ed. Volumes 1-3. New York, NY: Van Nostrand Reinhold, 1996., p. 2174] **PEER REVIEWED**

Strong oxidizers. [NIOSH. NIOSH Pocket Guide to Chemical Hazards & Other Databases CD-ROM. Department of Health & Human Services, Centers for Disease Prevention & Control. National Institute for Occupational Safety& Health. DHHS (NIOSH) Publication No. 2004-103 (2003).] **PEER

REVIEWED**

/Acetyl bromide/ interaction with... methanol... is violent, hydropgen bromide being evolved. [Bretherick, L. Handbook of Reactive Chemical Hazards. 4th ed. Boston, MA: Butterworth-Heinemann Ltd., 1990, p. 243]

**PEER REVIEWED**

Accidental use of methanol in place of hexane to rinse out a hypodermic syringe used for a diulte alkylaluminium solution caused a violent reaction which blew the plunger out of the barrel. [Bretherick, L. Handbook of Reactive Chemical Hazards. 4th ed. Boston, MA: Butterworth-Heinemann Ltd., 1990, p. 174] **PEER REVIEWED**

Reaction of /beryllium hydride/ with methanol... is violent, even at -196 deg C. [Bretherick, L. Handbook of Reactive Chemical Hazards. 4th ed. Boston, MA: Butterworth-Heinemann Ltd., 1990, p. 86] **PEER REVIEWED**

The rapid autocatalytic dissolution of aluminum, magnesium or zinc in 9:1 methanol-carbon tetrachloride mixtures is sufficiently vigorous to be rated as potentially hazardous. [Bretherick, L. Handbook of Reactive Chemical Hazards. 4th ed. Boston, MA: Butterworth-Heinemann Ltd., 1990, p. 174] **PEER REVIEWED**

During attempted preparation of trimethyl orthoformate, addition of sodium to an inadequately cooled chloroform-methanol mixture caused a violent explosion. [Bretherick, L. Handbook of Reactive Chemical Hazards. 4th ed. Boston, MA: Butterworth-Heinemann Ltd., 1990, p. 133] **PEER REVIEWED**

A chloroform-methanol mixture was put into a drum contaminated with sodium hydroxide. A vigorous reaction set in and the drum burst. Chloroform normally reacts slowly with sodium hydroxide owing to the insolublility of the latter. The presence of methanol increases the rate of reaction by increasing the degree of ocntact between chloroform and alkali. Addition of chloroform to a 4:1 mixture of methanol and 50 w/v% sodium hydroxide solution caused the drum to burst. [Bretherick, L. Handbook of Reactive Chemical Hazards. 4th ed. Boston, MA: Butterworth-Heinemann Ltd., 1990, p. 133] **PEER REVIEWED**

A crust of residual cynauric chloride left in a reactor from a previous batch reacted with the methanol (usually charged first) to form hydrogen chloride. When the base was added (usually before the chloride), vigorous evolution of carbon dioxide expelled some of the solvent. In a second incident, accidentally boubling the charge of cyanuric chloride but not 

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2/24/2011 htt p ://toxnet.nlm.nih. g ov/c g i- b in/sis/download.txtthe base, led to the development of free acid (which auto-catalyses the reaction with methanol), and a runaway reaction developed causing violent boiling of the solvent, methyl chloride evolution and damage to the plant. [Bretherick, L. Handbook of Reactive Chemical Hazards. 4th ed. Boston, MA: Butterworth-Heinemann Ltd., 1990, p. 333] **PEER REVIEWED**

Dichloromethane, previously considered to be non-flammable except in oxygen, becomes flammable in air... at 27 deg C/1 bar in presence of less than 0.5 vol% of methanol. [Bretherick, L. Handbook of Reactive Chemical Hazards. 4th ed. Boston, MA: Butterworth-Heinemann Ltd., 1990, p. 141]

**PEER REVIEWED**

Interaction /of diethylzinc and methanol/ is explosively violent and ignition ensues. [Bretherick, L. Handbook of Reactive Chemical Hazards. 4th ed. Boston, MA: Butterworth-Heinemann Ltd., 1990, p. 493] **PEER

REVIEWED**

/There is an/ explosive nature of mixtures of aluminum or magnesium with methanol... [Bretherick, L. Handbook of Reactive Chemical Hazards. 4th ed. Boston, MA: Butterworth-Heinemann Ltd., 1990, p. 28] **PEER REVIEWED**

The reaction of magnesium and methanol to form magnesium methoxide and used to prepare dry methanol is very vigorous, but often subject to a lengthy induction period. Sufficient methanol must be present to absorb the violent exotherm which sometimes occurs. Mixtures of powdered magnesium (or aluminum) and methanol are capable of detonation and are more powerful than military explosives. [Bretherick, L. Handbook of Reactive Chemical Hazards. 4th ed. Boston, MA: Butterworth-Heinemann Ltd., 1990, p. 1323] **PEER REVIEWED**

Passage of chlorine through cold recovered methanol (but not fresh methanol) led to a mild explosion and ignition, formation of methyl hypochlorite apparently being catalysed by an impurity. [Bretherick, L. Handbook of Reactive Chemical Hazards. 4th ed. Boston, MA: Butterworth-Heinemann Ltd., 1990, p. 1004] **PEER REVIEWED**

When methanol was used to rinse a pestle and mortar which had been used to grind coarse chromium trioxide, immediate ignition occurred due to vigorous oxidation of the solvent. [Bretherick, L. Handbook of Reactive Chemical Hazards. 4th ed. Boston, MA: Butterworth-Heinemann Ltd., 1990, p. 1069] **PEER REVIEWED**

The explosion limits have been determined for liquid systems containing... methanol... under various types of initiation. In general, explosive behavior is noted where the ratio of hydrogen peroxide to water is > 1, and if the overall fuel-peroxide composition is stoicheiometric... . [Bretherick, L. Handbook of Reactive Chemical Hazards. 4th ed. Boston, MA: Butterworth-Heinemann Ltd., 1990, p. 1212] **PEER REVIEWED**

A saturated solution of anhydrous lead perchlorate in dry methanol exploded violently when disturbed. [Bretherick, L. Handbook of Reactive Chemical Hazards. 4th ed. Boston, MA: Butterworth-Heinemann Ltd., 1990, p. 1030] **PEER REVIEWED**

Furfuryl alcohol is hypergolic with high-strength nitric acid and methanol has been used as a propellant fuel. [Bretherick, L. Handbook of Reactive Chemical Hazards. 4th ed. Boston, MA: Butterworth-Heinemann Ltd., 1990, p. 1150] **PEER REVIEWED**

Several explosions involving methanol and sodium hypochlorite were attributed to formation of methyl hypochlorite, especially in presence of acids or other esterification catalyst. [Bretherick, L. Handbook of Reactive Chemical Hazards. 4th ed. Boston, MA: Butterworth-Heinemann Ltd., 1990, p. 985] **PEER REVIEWED**

Liquid /phosphorous (III) oxide/ (above 24 deg C) reacts very violently with methanol... and charring may occur. [Bretherick, L. Handbook of Reactive Chemical Hazards. 4th ed. Boston, MA: Butterworth-Heinemann Ltd., 1990, p. 1431] **PEER REVIEWED**

Contact of 1.5g portions of solid /potassium tert-butoxide/ with drops of /methanol/ or with the vapors of /methanol/ caused ignition... [Bretherick, L. Handbook of Reactive Chemical Hazards. 4th ed. Boston, MA: Butterworth-Heinemann Ltd., 1990, p. 475] **PEER REVIEWED**

Static discharge ignited the contents of a polythene bottle being filled with a 40:60 mixture of methanol and water at 30 deg C, and a later similar incident in a plastics-lined metal tank involved a 30:70 mixture [Bretherick, L. Handbook of Reactive Chemical Hazards. 4th ed. Boston, MA: Butterworth-Heinemann Ltd., 1990, p. 175] **PEER REVIEWED**

HAZARDOUS DECOMPOSITION: When heated to decomposition it emits acrid smoke and irritating fumes. [Lewis, R.J. Sax's Dangerous Properties of Industrial Materials. 9th ed. Volumes 1-3. New York, NY: Van Nostrand Reinhold, 1996., p. 2175] **PEER

REVIEWED**

PRIOR HISTORY OF ACCIDENTS: An outbreak of acute methanol intoxication involving 28 young men in Papua New Guinea in 1977, each of whom consumed an equivalent of 60-600 mL pure methanol, resulted in all becoming hospitalized within 8-36 hr due to 

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2/24/2011 htt p ://toxnet.nlm.nih. g ov/c g i- b in/sis/download.txtacute metabolic acidosis, severe visual impairment and acute pancreatitis. Four died within 72 hr after hospitalization. Of 24 who recovered, 16 showed no residual complications, 6 had bilateral visual impairment and 2 had difficulty in speech as well as visual impairment. [WHO; Environ Health Criteria 196: Methanol p.101 (1997). Available from, as of July 18, 2005: http://www.inchem.org/documents/ehc/ehc/ehc196.htm] **PEER

REVIEWED**

...In Atlanta, Georgia, USA, in 1951, when within a 5-day period, 323 people consumed bootlegged whiskey contaminated with 35-40% methanol and 41 of them died. ...The poisoning of 18 individuals /was reported/, of whom 8 died, when a diluted paint thinner containing approximately 37% (by volume) methanol was used as an alcoholic beverage in Lexington, Kentucky, USA. An epidemic in the State Prison of Southern Michigan in 1979 in which methanol diluent used in photocopying machines was used as "home-made" spirits (containing approximately 3% methanol) resulted in 46 definite cases of methanol intoxication and 3 deaths. Methanol poisoning among 23 servicemen in an Army hospital in Korea who had ingested bootleg sake contaminated with methanol was reported. ...Acute methanol poisoning in 49 naval personnel who consumed drinks made from duplicating fluid containing a high concentration of methanol /was also reported/. [WHO; Environ Health Criteria 196: Methanol p.101 (1997). Available from, as of July 18, 2005: http://www.inchem.org/documents/ehc/ehc/ehc196.htm] **PEER REVIEWED**

IMMEDIATELY DANGEROUS TO LIFE OR HEALTH: 6000 ppm [NIOSH. NIOSH Pocket Guide to Chemical Hazards & Other Databases CD-ROM. Department of Health & Human Services, Centers for Disease Prevention & Control. National Institute for Occupational Safety& Health. DHHS (NIOSH) Publication No. 2004-103 (2003).] **PEER

REVIEWED**

PROTECTIVE EQUIPMENT & CLOTHING: Wear appropriate chemical protective gloves, boots, and goggles. [Association of American Railroads/Bureau of Explosives; Emergency Handling of Hazardous Materials in Surface Transportation. Association of American Railroads. Pueblo, CO. 2002., p. 586] **PEER REVIEWED**

There is some data suggesting that the breakthrough times of methanol through natural rubber are approximately an hour or more. [ACGIH; Guidelines Select of Chem Protect Clothing Volume #1 Field Guide p.61 (1983)] **PEER REVIEWED**

Breakthrough times of methanol through nitrile or Viton are greater than one hour reported by (normally) two or more testers. [ACGIH; Guidelines Select of Chem Protect Clothing Volume #1 Field Guide p.61 (1983)] **PEER

REVIEWED**

Breakthrough times of methanol through polyvinyl alcohol or polyvinyl chloride are less (usually significantly less) than one hour reported by (normally) two or more testers. [ACGIH; Guidelines Select of Chem Protect Clothing Volume #1 Field Guide p.61 (1983)] **PEER REVIEWED**

Respirator Recommendations: Up to 2000 ppm: (Assigned Protection Factor = 10) Any supplied-air respirator. [NIOSH. NIOSH Pocket Guide to Chemical Hazards & Other Databases CD-ROM. Department of Health & Human Services, Centers for Disease Prevention & Control. National Institute for Occupational Safety& Health. DHHS (NIOSH) Publication No. 2004-103 (2003).] **PEER REVIEWED**

Respirator Recommendations: Up to 5000 ppm: (Assigned Protection Factor = 25) Any supplied-air respirator operated in a continuous-flow mode. [NIOSH. NIOSH Pocket Guide to Chemical Hazards & Other Databases CD-ROM. Department of Health & Human Services, Centers for Disease Prevention & Control. National Institute for Occupational Safety& Health. DHHS (NIOSH) Publication No. 2004-103 (2003).] **PEER REVIEWED**

Respirator Recommendations: Up to 6000 ppm: (Assigned Protection Factor = 50) Any supplied-air respirator that has a tight-fitting facepiece and is operated in a continuous-flow mode/(Assigned Protection Factor = 50) Any self-contained breathing apparatus with a full facepiece/(Assigned Protection Factor = 50) Any supplied-air respirator with a full facepiece. [NIOSH. NIOSH Pocket Guide to Chemical Hazards & Other Databases CD-ROM. Department of Health & Human Services, Centers for Disease Prevention & Control. National Institute for Occupational Safety& Health. DHHS (NIOSH) Publication No. 2004-103 (2003).] **PEER REVIEWED**

Respirator Recommendations: Emergency or planned entry into unknown concentrations or IDLH conditions: (Assigned Protection Factor = 10,000) Any self-contained breathing apparatus that has a full facepiece and is operated in a pressure-demand or other positive-pressure mode/(Assigned Protection Factor = 10,000) Any supplied-air respirator that has a full facepiece and is operated in a pressure-demand or other positive-pressure mode in combination with an auxiliary self-contained positive-pressure breathing apparatus. [NIOSH. NIOSH Pocket Guide to Chemical Hazards & Other Databases CD-ROM. Department of Health & Human Services, Centers for Disease Prevention & Control. National Institute for Occupational Safety& Health. DHHS (NIOSH) Publication No. 2004-103 (2003).] **PEER

REVIEWED**

Respirator Recommendations: Escape: Any appropriate escape-type, self-contained breathing apparatus. [NIOSH. NIOSH Pocket Guide to Chemical 

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2/24/2011 htt p ://toxnet.nlm.nih. g ov/c g i- b in/sis/download.txtHazards & Other Databases CD-ROM. Department of Health & Human Services, Centers for Disease Prevention & Control. National Institute for Occupational Safety& Health. DHHS (NIOSH) Publication No. 2004-103 (2003).] **PEER REVIEWED**

Wear appropriate personal protective clothing to prevent skin contact. [NIOSH. NIOSH Pocket Guide to Chemical Hazards & Other Databases CD-ROM. Department of Health & Human Services, Centers for Disease Prevention & Control. National Institute for Occupational Safety& Health. DHHS (NIOSH) Publication No. 2004-103 (2003).] **PEER REVIEWED**

Wear appropriate eye protection to prevent eye contact. [NIOSH. NIOSH Pocket Guide to Chemical Hazards & Other Databases CD-ROM. Department of Health & Human Services, Centers for Disease Prevention & Control. National Institute for Occupational Safety& Health. DHHS (NIOSH) Publication No. 2004-103 (2003).] **PEER REVIEWED**

PREVENTIVE MEASURES: Skin that becomes wet with liquid methyl alcohol should be promptly washed or showered. Eating and smoking should not be permitted in areas where liquid methyl alcohol is handled, processed, or stored. [Mackison, F. W., R. S. Stricoff, and L. J. Partridge, Jr. (eds.). NIOSH/OSHA - Occupational Health Guidelines for Chemical Hazards. DHHS(NIOSH) Publication No. 81-123 (3 VOLS). Washington, DC: U.S. Government Printing Office, Jan. 1981., p. 2] **PEER REVIEWED**

SRP: The scientific literature for the use of contact lenses in industry is conflicting. The benefit or detrimental effects of wearing contact lenses depend not only upon the substance, but also on factors including the form of the substance, characteristics and duration of the exposure, the uses of other eye protection equipment, and the hygiene of the lenses. However, there may be individual substances whose irritating or corrosive properties are such that the wearing of contact lenses would be harmful to the eye. In those specific cases, contact lenses should not be worn. In any event, the usual eye protection equipment should be worn even when contact lenses are in place. **PEER REVIEWED**

If material not on fire and not involved in fire: Keep sparks, flames, and other sources of ignition away. Keep material out of water sources and sewers. Build dikes to contain flow as necessary. Attempt to stop leak if without undue personnel hazard. Use water spray to disperse vapors and dilute standing pools of liquid. [Association of American Railroads/Bureau of Explosives; Emergency Handling of Hazardous Materials in Surface Transportation. Association of American Railroads. Pueblo, CO. 2002., p. 586] **PEER REVIEWED**

Before welding or cutting a vessel that has contained methyl alcohol, the vessel should be emptied and purged to remove every trace of the flammable liquid. [International Labour Office. Encyclopedia of Occupational Health and Safety. Vols. I&II. Geneva, Switzerland: International Labour Office, 1983., p. 1357] **PEER REVIEWED**

A major concern in the painting studio is solvents, /including methanol/. ... Precautions include ... use of dilution and local exhaust ventilation, control of storage areas, disposal of solvent soaked rags in covered containers, minimizing skin exposure, and the use of respirators and other personal protective equipment. The control of fire hazards is also important, since many of the solvents are highly flammable. [Hart C; J of Environ Health 49 (5): 282-6 (1987)] **PEER REVIEWED**

Personnel protection: Avoid breathing vapors. Keep upwind. Do not handle broken packages unless wearing appropriate personal protective equipment. Wash away any material which may have contacted the body with copious amounts of water or soap and water. [Association of American Railroads/Bureau of Explosives; Emergency Handling of Hazardous Materials in Surface Transportation. Association of American Railroads. Pueblo, CO. 2002., p. 586] **PEER REVIEWED**

The worker should immediately wash the skin when it becomes contaminated. [NIOSH. NIOSH Pocket Guide to Chemical Hazards & Other Databases CD-ROM. Department of Health & Human Services, Centers for Disease Prevention & Control. National Institute for Occupational Safety& Health. DHHS (NIOSH) Publication No. 2004-103 (2003).] **PEER REVIEWED**

Work clothing that becomes wet should be immediately removed due to its flammability hazard. [NIOSH. NIOSH Pocket Guide to Chemical Hazards & Other Databases CD-ROM. Department of Health & Human Services, Centers for Disease Prevention & Control. National Institute for Occupational Safety& Health. DHHS (NIOSH) Publication No. 2004-103 (2003).] **PEER

REVIEWED**

If material on fire or involved in fire: Do not extinguish fire unless flow can be stopped. Use water in flooding quantities as fog. Solid streams of water may be ineffective. Cool all affected containers with flooding quantities of water. Apply water from as far a distance as possible. Use 'alcohol' foam, dry chemical, or carbon dioxide. [Association of American Railroads/Bureau of Explosives; Emergency Handling of Hazardous Materials in Surface Transportation. Association of American Railroads. Pueblo, CO. 2002., p. 586] **PEER REVIEWED**

SRP: Local exhaust ventilation should be applied wherever there is an 

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2/24/2011 htt p ://toxnet.nlm.nih. g ov/c g i- b in/sis/download.txtincidence of point source emissions or dispersion of regulated

contaminants in the work area. Ventilation control of the contaminant as close to its point of generation is both the most economical and safest method to minimize personnel exposure to airborne contaminants. **PEER

REVIEWED**

SRP: Contaminated protective clothing should be segregated in such a manner so that there is no direct personal contact by personnel who handle, dispose, or clean the clothing. Quality assurance to ascertain the completeness of the cleaning procedures should be implemented before the decontaminated protective clothing is returned for reuse by the workers. Contaminated clothing should not be taken home at end of shift, but should remain at employee's place of work for cleaning. **PEER REVIEWED**

SHIPMENT METHODS AND REGULATIONS: No person may /transport,/ offer or accept a hazardous material for transportation in commerce unless that person is registered in conformance ... and the hazardous material is properly classed, described, packaged, marked, labeled, and in condition for shipment as required or authorized by ... /the hazardous materials regulations (49 CFR 171-177)./ [49 CFR

171.2; U.S. National Archives and Records Administration's Electronic Code of Federal Regulations. Available from, as of February 15, 2006: http://www.gpoaccess.gov/ecfr/] **PEER REVIEWED**

The International Air Transport Association (IATA) Dangerous Goods Regulations are published by the IATA Dangerous Goods Board pursuant to IATA Resolutions 618 and 619 and constitute a manual of industry carrier regulations to be followed by all IATA Member airlines when transporting hazardous materials. [International Air Transport Association. Dangerous Goods Regulations. 47th Edition. Montreal, Quebec Canada. 2006., p. 217]

**PEER REVIEWED**

The International Maritime Dangerous Goods Code lays down basic principles for transporting hazardous chemicals. Detailed recommendations for individual substances and a number of recommendations for good practice are included in the classes dealing with such substances. A general index of technical names has also been compiled. This index should always be consulted when attempting to locate the appropriate procedures to be used when shipping any substance or article. [International Maritime Organization. International Maritime Dangerous Goods Code. London, UK. 2004., p. 53] **PEER REVIEWED**

CLEANUP METHODS: General Spill Actions: Stop or reduce discharge of material if this can be done without risk. Eliminate all sources of ignition. Avoid skin contact and inhalation. A fluorocarbon water foam can be applied to the spill to diminish vapor and fire hazard. Hycar and carbopol, which are absorbent materials, have shown possible applicability for vapor suppression and/or containment of methanol in spill situations. Leaking containers should be removed to the outdoors or to an isolated, well-ventilated area and the contents transferred to other suitable containers. The following materials are recommended for plugging leaks of methanol: polyester (eg Glad bag), imid polyester (eg brown-in-bag), stafoam urethane foam, sea-going epoxy putty, and MSA urethane. [Environment Canada; Tech Info for Problem Spills: Methanol (Draft) p.98 (1981)] **PEER REVIEWED**

Spills on Land: Contain if possible by forming mechanical or chemical barriers to prevent spreading. Absorb on sand, vermiculite or other absorbent and shovel into metal containers for disposal. Application of universal gelling agent to immobilize the spill, or the use of fly ash or cement powder to absorb the liquid bulk should also be considered. Other

recommended sorbent materials are activated carbon and a universal sorbent material. [Environment Canada; Tech Info for Problem Spills: Methanol (Draft) p.98 (1981)] **PEER REVIEWED**

Spills in Water: After containment, a universal gelling agent can be injected to solidify trapped mass to increase the effectiveness of berms. Activated carbon can be applied at 10% the spilled amount over region occupied by 10 mg/L or greater concentrations. Then use mechanical dredges or lifts to remove immobilized masses of pollutants. [Environment Canada; Tech Info for Problem Spills: Methanol (Draft) p.98 (1981)] **PEER

REVIEWED**

If the spilled material is known to be methanol: Response personnel should be provided with and required to use impervious clothing, gloves, face shields (eight-inch minimum), and other appropriate protective clothing necessary to prevent repeated or prolonged skin contact with liquid methyl alcohol. Splash-proof and chemical safety goggles are recommended for eye protection. Polyvinyl plastic, neoprene or rubber is recommended for protective clothing and gloves. Chemical suit materials recommended for protection against methanol, include butyl, neoprene and polyvinyl chloride. [Environment Canada; Tech Info for Problem Spills: Methanol (Draft) p.100 (1981)] **PEER REVIEWED**

Environmental considerations- Land spill: Dig a pit, pond, lagoon, holding area to contain liquid or solid material. /SRP: If time permits, pits, ponds, lagoons, soak holes, or holding areas should be sealed with an impermeable flexible membrane liner./ Dike surface flow using soil, sand bags, foamed polyurethane, or foamed concrete. [Association of American Railroads/Bureau of Explosives; Emergency Handling of Hazardous Materials in Surface Transportation. Association of American Railroads. Pueblo, CO. 

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Environmental considerations- Water spill: Allow to aerate. Use natural barriers or oil spill control booms to limit spill travel. Remove trapped material with suction hoses. [Association of American Railroads/Bureau of Explosives; Emergency Handling of Hazardous Materials in Surface Transportation. Association of American Railroads. Pueblo, CO. 2002., p. 586] **PEER REVIEWED**

Environmental considerations- Air spill: Apply water spray or mist to knock down vapors. [Association of American Railroads/Bureau of Explosives; Emergency Handling of Hazardous Materials in Surface Transportation. Association of American Railroads. Pueblo, CO. 2002., p. 586] **PEER REVIEWED**

DISPOSAL METHODS: Generators of waste (equal to or greater than 100 kg/mo) containing this contaminant, EPA hazardous waste numbers U154 and F003, must conform with USEPA regulations in storage, transportation, treatment and disposal of waste. [40 CFR 240-280, 300-306, 702-799 (7/1/2004)] **PEER REVIEWED**

Disposal: Waste methanol must never be discharged directly into sewers or surface waters. Large quantities of waste methanol can either be disposed of at licensed waste solvent disposal company or reclaimed by filtration and distillation. It can also be incinerated. [Environment Canada; Tech Info for Problem Spills: Methanol (Draft) p.100 (1981)] **PEER REVIEWED**

A good candidate for rotary kiln incineration at a temperature range of 820 to 1,600 deg C and residence times of seconds for liquids and gases, and hours for solids. A good candidate for liquid injection incineration at a temperature range of 650 to 1,600 deg C and a residence time of 0.1 to 2 seconds. A good candidate for fluidized bed incineration at a temperature range of 450 to 980 deg C and residence times of seconds for liquids and gases, and longer for solids. [USEPA; Engineering Handbook for Hazardous Waste Incineration p.3-14 (1981) EPA 68-03-3025] **PEER

REVIEWED**

The following wastewater treatment technologies have been investigated for methanol biological treatment, reverse osmosis, and activated carbon. [USEPA; Management of Hazardous Waste Leachate, EPA Contract No.68-03-2766 p.E-16 (1982)] **PEER REVIEWED**

Spray into a furnace. Incineration will become easier by mixing with a more flammable solvent. Recommendable methods: Incineration... . [United Nations. Treatment and Disposal Methods for Waste Chemicals (IRPTC File). Data Profile Series No. 5. Geneva, Switzerland: United Nations Environmental Programme, Dec. 1985., p. 209] **PEER REVIEWED**

OCCUPATIONAL EXPOSURE STANDARDS:

OSHA STANDARDS: Permissible Exposure Limit: Table Z-1 8-hr Time Weighted Avg: 200 ppm (260 mg/cu m). [29 CFR 1910.1000; U.S. National Archives and Records Administration's Electronic Code of Federal Regulations. Available from, as of June 1, 2005: http://www.gpoaccess.gov/ecfr] **PEER REVIEWED**

Vacated 1989 OSHA PEL TWA 200 ppm (260 mg/cu m); STEL 250 ppm (325 mg/cu m), skin designation, is still enforced in some states. [NIOSH. NIOSH Pocket Guide to Chemical Hazards. DHHS (NIOSH) Publication No. 97-140. Washington, D.C. U.S. Government Printing Office, 1997., p. 367] **PEER

REVIEWED**

THRESHOLD LIMIT VALUES: 8 hr Time Weighted Avg (TWA): 200 ppm; 15 min Short Term Exposure Limit (STEL): 250 ppm. Skin. [American Conference of Governmental Industrial Hygienists TLVs and BEIs. Threshold Limit Values for Chemical Substances and Physical Agents and Biological Exposure Indices. Cincinnati, OH, 2008, p. 38] **QC REVIEWED**

Biological Exposure Index (BEI): Determinant: methanol in urine; Sampling Time: end of shift; BEI: 15 mg/L. The determinant may be present in biological specimens collected from subjects who have not been occupationally exposed, at a concentration which could affect interpretation of the result. Such background concentrations are incorporated in the BEI value. The determinant is nonspecific, since it is also observed after exposure to other chemicals. [American Conference of Governmental Industrial Hygienists TLVs and BEIs. Threshold Limit Values for Chemical Substances and Physical Agents and Biological Exposure Indices. Cincinnati, OH, 2008, p. 106] **QC REVIEWED**

NIOSH RECOMMENDATIONS: Recommended Exposure Limit: 10 Hr Time-Weighted Avg: 200 ppm (260 mg/cu m), 15 Min Short-Term Exposure Limit: 250 ppm (325 mg/cu m), skin. [NIOSH. NIOSH Pocket Guide to Chemical Hazards & Other Databases CD-ROM. Department of Health & Human Services, Centers for Disease Prevention & Control. National Institute for Occupational Safety& Health. DHHS (NIOSH) Publication No. 2004-103 (2003).] **PEER REVIEWED**

IMMEDIATELY DANGEROUS TO LIFE OR HEALTH: 

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2/24/2011 htt p ://toxnet.nlm.nih. g ov/c g i- b in/sis/download.txt6000 ppm [NIOSH. NIOSH Pocket Guide to Chemical Hazards & Other Databases CD-ROM. Department of Health & Human Services, Centers for Disease Prevention & Control. National Institute for Occupational Safety& Health. DHHS (NIOSH) Publication No. 2004-103 (2003).] **PEER

REVIEWED**

OTHER STANDARDS REGULATIONS AND GUIDELINES: Arab Republic of Egypt TWA 200 ppm (260 mg/cu m), skin [Bingham, E.; Cohrssen, B.; Powell, C.H.; Patty's Toxicology Volumes 1-9 5th ed. John Wiley & Sons. New York, N.Y. (2001)., p. V8 p.1284] **PEER REVIEWED**

Australia TWA 200 ppm (260 mg/cu m); STEL 250 ppm, skin [Bingham, E.; Cohrssen, B.; Powell, C.H.; Patty's Toxicology Volumes 1-9 5th ed. John Wiley & Sons. New York, N.Y. (2001)., p. V8 p.1284] **PEER REVIEWED**

Beligium TWA 200 ppm (260 mg/cu m); STEL 250 ppm, skin [Bingham, E.; Cohrssen, B.; Powell, C.H.; Patty's Toxicology Volumes 1-9 5th ed. John Wiley & Sons. New York, N.Y. (2001)., p. V8 p.1284] **PEER REVIEWED**

Denmark TWA 200 (260 mg/cu m), skin [Bingham, E.; Cohrssen, B.; Powell, C.H.; Patty's Toxicology Volumes 1-9 5th ed. John Wiley & Sons. New York, N.Y. (2001)., p. V8 p.1284] **PEER REVIEWED**

Finland TWA 200 (260 mg/cu m); STEL 250 ppm, skin [Bingham, E.; Cohrssen, B.; Powell, C.H.; Patty's Toxicology Volumes 1-9 5th ed. John Wiley & Sons. New York, N.Y. (2001)., p. V8 p.1285] **PEER REVIEWED**

France TWA 200 (260 mg/cu m); STEL 1000 ppm (1300 mg/cu m), skin [Bingham, E.; Cohrssen, B.; Powell, C.H.; Patty's Toxicology Volumes 1-9 5th ed. John Wiley & Sons. New York, N.Y. (2001)., p. V8 p.1285]

**PEER REVIEWED**

Germany (DFG MAK) TWA 200 (270 mg/cu m) [Bingham, E.; Cohrssen, B.; Powell, C.H.; Patty's Toxicology Volumes 1-9 5th ed. John Wiley & Sons. New York, N.Y. (2001)., p. V8 p.1285] **PEER REVIEWED**

Hungary 50 mg/cu m; STEL 100 mg/cu m, skin [Bingham, E.; Cohrssen, B.; Powell, C.H.; Patty's Toxicology Volumes 1-9 5th ed. John Wiley & Sons. New York, N.Y. (2001)., p. V8 p.1285] **PEER REVIEWED**

Ireland TWA 200 ppm (260 mg/cu m); STEL 250 ppm (310 mg/cu m), skin [Bingham, E.; Cohrssen, B.; Powell, C.H.; Patty's Toxicology Volumes 1-9 5th ed. John Wiley & Sons. New York, N.Y. (2001)., p. V8 p.1285]

**PEER REVIEWED**

Japan (JSOH) TWA 200 ppm (260 mg/cu m), skin [Bingham, E.; Cohrssen, B.; Powell, C.H.; Patty's Toxicology Volumes 1-9 5th ed. John Wiley & Sons. New York, N.Y. (2001)., p. V8 p.1285] **PEER REVIEWED**

The Netherlands TWA 200 ppm (260 mg/cu m), skin [Bingham, E.; Cohrssen, B.; Powell, C.H.; Patty's Toxicology Volumes 1-9 5th ed. John Wiley & Sons. New York, N.Y. (2001)., p. V8 p.1285] **PEER REVIEWED**

The Philippines TWA 200 ppm (260 mg/cu m) [Bingham, E.; Cohrssen, B.; Powell, C.H.; Patty's Toxicology Volumes 1-9 5th ed. John Wiley & Sons. New York, N.Y. (2001)., p. V8 p.1285] **PEER REVIEWED**

Poland TWA 100 ppm; STEL 300 mg/cu m, skin [Bingham, E.; Cohrssen, B.; Powell, C.H.; Patty's Toxicology Volumes 1-9 5th ed. John Wiley & Sons. New York, N.Y. (2001)., p. V8 p.1285] **PEER REVIEWED**

Russia TWA 200 ppm; STEL 5 mg/cu m, skin [Bingham, E.; Cohrssen, B.; Powell, C.H.; Patty's Toxicology Volumes 1-9 5th ed. John Wiley & Sons. New York, N.Y. (2001)., p. V8 p.1285] **PEER REVIEWED**

Sweden TWA 200 ppm (250 mg/cu m); STEL 250 ppm (350 mg/cu m), skin [Bingham, E.; Cohrssen, B.; Powell, C.H.; Patty's Toxicology Volumes 1-9 5th ed. John Wiley & Sons. New York, N.Y. (2001)., p. V8 p.1285]

**PEER REVIEWED**

Switzerland TWA 200 ppm (260 mg/cu m); STEL 400 ppm, skin [Bingham, E.; Cohrssen, B.; Powell, C.H.; Patty's Toxicology Volumes 1-9 5th ed. John Wiley & Sons. New York, N.Y. (2001)., p. V8 p.1285] **PEER REVIEWED**

Thailand TWA 200 ppm (260 mg/cu m) [Bingham, E.; Cohrssen, B.; Powell, C.H.; Patty's Toxicology Volumes 1-9 5th ed. John Wiley & Sons. New York, N.Y. (2001)., p. V8 p.1285] **PEER REVIEWED**

Turkey TWA 200 ppm (260 mg/cu m) [Bingham, E.; Cohrssen, B.; Powell, C.H.; Patty's Toxicology Volumes 1-9 5th ed. John Wiley & Sons. New York, N.Y. (2001)., p. V8 p.1285] **PEER REVIEWED**

United Kingdom TWA 200 ppm (260 mg/cu m); STEL/CEIL (C) 250 ppm (333 mg/cu m) [Bingham, E.; Cohrssen, B.; Powell, C.H.; Patty's Toxicology Volumes 1-9 5th ed. John Wiley & Sons. New York, N.Y. (2001)., p. V8 p.1285]

**PEER REVIEWED**

Emergency Response Planning Guidelines (ERPG): ERPG(1) 200 ppm (no more than mild, transient effects) for up to 1 hr exposure; ERPG(2) 1000 ppm (without serious, adverse effects) for up to 1 hr exposure; ERPG(3) 5000 ppm (not life threatening) up to 1 hr exposure. [American Industrial 

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2/24/2011 htt p ://toxnet.nlm.nih. g ov/c g i- b in/sis/download.txtHygiene Association. The AIHA 2005 Emergency Response Planning Guidelines and Workplace Environmental Exposure Level Handbook. AIHA. Fairfax, VA 2005., p. 23] **PEER REVIEWED**

MANUFACTURING/USE INFORMATION:

MAJOR USES: For methanol (USEPA/OPP Pesticide Code: 053801) there are 0 labels match. /SRP: Not registered for current use in the U.S., but approved pesticide uses may change periodically and so federal, state and local authorities must be consulted for currently approved uses./ [U.S. Environmental Protection Agency/Office of Pesticide Program's Chemical Ingredients Database on Methanol (67-56-1). Available from, as of June 1, 2005: http://ppis.ceris.purdue.edu/htbin/epachem.com] **PEER REVIEWED**

Industrial solvent. Raw material for making formaldehyde and methyl esters of organic and inorganic acids. Antifreeze for automotive radiators and brakes; ingredient of gasoline and diesel oil antifreezes. Octane booster in gasoline. As fuel for picnic stoves and soldering torches. Extractant for animal and vegetable oils. To denature ethanol. Softening agent for pyroxylin plastics. Solvent and solvent adjuvant for polymers. Solvent in the manufacture of cholesterol, streptomycin, vitamins, hormones, and other pharmaceuticals. [O'Neil, M.J. (ed.). The Merck Index - An Encyclopedia of Chemicals, Drugs, and Biologicals. 13th Edition, Whitehouse Station, NJ: Merck and Co., Inc., 2001., p. 1065] **PEER

REVIEWED**

Used in dehydrating pipelines, as a de-icing agent, and in the production of methylamines and chlorine dioxide. [Environment Canada; Tech Info for Problem Spills: Methanol (Draft) p.15 (1981)] **PEER REVIEWED**

Primarily as substitute solvent and rubefacient for ethyl alcohol in liniments (external use only). [Rossoff, I.S. Handbook of Veterinary Drugs. New York: Springer Publishing Company, 1974., p. 8] **PEER

REVIEWED**

Used on household contents, mortuary instruments, bedding (human), human clothing, tissues (biological specimens), cadavers, and human stools against animal pathogenic bacteria (gram- and gram+ vegetative) and maggots. /Eureka Products, Criosine/ [Purdue University; National Pesticide Information Retrieval System (1988)] **PEER REVIEWED**

Used in oil recovery packer fluid against slime forming bacteria, deterioration and spoilage bacteria, sulfate-reducing bacteria. /Coat-B1400/ [Purdue University; National Pesticide Information Retrieval System (1988)] **PEER REVIEWED**

Used on onions during soil treatment against onion smut (urocystis cepulae). /Wilbur-Ellis Smut-Guard/ [Purdue University; National Pesticide Information Retrieval System (1988)] **PEER REVIEWED**

Used on elms as injection treatment against dutch elm disease. /Freers Elm Arrester/ [Purdue University; National Pesticide Information Retrieval System (1988)] **PEER REVIEWED**

Used in secondary oil recovery injection water against slime forming bacteria. /Surflo-B17/ [Purdue University; National Pesticide Information Retrieval System (1988)] **PEER REVIEWED**

Used on timbers, wood fence posts, wood poles/posts, timbers (heavy wooden members), and lumber (seasoned) for soil contact nonfumigation treatment against wood rot and decay fungi. /Ideal Concentrated Wood-Preservative/ [Purdue University; National Pesticide Information Retrieval System (1988)] **PEER REVIEWED**

... Duplicating fluid (99% methyl alcohol) used in direct-process spirit duplicating machines [Frederick LJ et al; Am Ind Hyg Assoc J 45 (1): 51-55 (1984)] **PEER REVIEWED** <a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=6702599" target=new>PubMed Abstract

Effective solvent for the removal of 2,4-dinitrotoluene from spent carbons [Ho PC, Daw CS; Environ Sci Technol 22 (8): 919-24 (1988)] **PEER

REVIEWED**

Removal of toxic organic pollutants from soil with supercritical carbon dioxide and methanol or toluene. [USEPA; Proc Int Conf New Front Hazard Waste Manage 2nd Ed. p.383-97 (1987) EPA/600/9-87/018F] **PEER REVIEWED**

About 70% of methanol manufactured worldwide is used as feedstock for the production of chemicals such as formaldehyde, methyl tertiary butyl ether (MTBE), acetic acid, methyl methacrylate, and dimethyl terephthalate. [DHHS/NTP; NTP-CERHR Expert Panel Report on the Reproductive and Developmental Toxicity of Methanol p.2 (April 2002) NTP-CERHR-MeOH-02. Available from, as of July 20, 2005: http://cerhr.niehs.nih.gov/news/methanol/methanol_final.pdf] **PEER

REVIEWED**

MANUFACTURERS: 

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2/24/2011 htt p ://toxnet.nlm.nih. g ov/c g i- b in/sis/download.txtAir Products and Chemicals, Inc., 7201 Hamilton Blvd., Allentown, PA 18195-1501, (610) 481-6799; Industrial Chemicals Division; Production site: Pace, FL 32571 [SRI Consulting. 2004 Directory of Chemical Producers. SRI International, Menlo Park, CA 2004., p. 721] **PEER

REVIEWED**

Celanese LTD., 86 Morris Avenue, Summit, NJ 07901, (872) 443-4000. Production sites: Bishop, TX 78343; Clear Lake, TX 77507 [SRI Consulting. 2004 Directory of Chemical Producers. SRI International, Menlo Park, CA 2004., p. 721] **PEER REVIEWED**

Dakota Gasification Company, 1600 East Interstate Avenue, P.O. Box 5540, Bismark, ND 58506-5540, (701) 221-4411; Production site: Beulah, ND 58523 [SRI Consulting. 2004 Directory of Chemical Producers. SRI International, Menlo Park, CA 2004., p. 721] **PEER REVIEWED**

Eastman Chemical Company, PO Box 511, Kingsport, TN 37662 (423) 229-2000; Production site: Kingsport, TN 37662 [SRI Consulting. 2004 Directory of Chemical Producers. SRI International, Menlo Park, CA 2004., p. 721]

**PEER REVIEWED**

Lyondell Methanol Company, One Houston Center, 1221 Mckinney St., Suite 1600, Houston, TX 77010 (713) 652-7000 Production site: Channelview, TX 77530 [SRI Consulting. 2004 Directory of Chemical Producers. SRI International, Menlo Park, CA 2004., p. 721] **PEER REVIEWED**

Millenium Petrochemicals, 11500 Northlake Drive, P.O. Box 429550, Cincinnati, OH 45249, (513)530-6500; Production site: LaPorte, TX 77571 [SRI Consulting. 2004 Directory of Chemical Producers. SRI International, Menlo Park, CA 2004., p. 721] **PEER REVIEWED**

Motiva Enterprises, 1100 Louisiana, Houston, TX 77002, (713) 277-8000; Production site: Delaware City, DE 19706 [SRI Consulting. 2004 Directory of Chemical Producers. SRI International, Menlo Park, CA 2004., p. 721]

**PEER REVIEWED**

Praxir Inc., 39 Old Ridgebury Rd., Danbury, CT 06810-5113, (716) 879-4077; Production site: Geismar, LA 70734 [SRI Consulting. 2004 Directory of Chemical Producers. SRI International, Menlo Park, CA 2004., p. 721]

**PEER REVIEWED**

Sterling Chemicals Inc., 1200 Smith St., Suite 1900, Houston, TX 77002-4312, (713) 650-3700; Production site: Texas City, TX 77590 [SRI Consulting. 2004 Directory of Chemical Producers. SRI International, Menlo Park, CA 2004., p. 721] **PEER REVIEWED**

Terra Industries Inc., Terra Centre, 600 Fourth St., Sioux City, IA 51101, (712) 277-7296; Production sites: Beaumont, TX 77704; Woodward, OK 73801 [SRI Consulting. 2004 Directory of Chemical Producers. SRI International, Menlo Park, CA 2004., p. 721] **PEER REVIEWED**

METHODS OF MANUFACTURING: Methanol is manufactured by the reaction between carbon monoxide and hydrogen at 503-673 deg K and 5-60 MPa (50-600 atm). High pressure processes (P greater than 150 atm) are catalyzed by copper chromite catalysts. The most widely used process, however, is the low pressure methanol process that is conducted at 503-523 deg K, 5-10 MPa (50-100 atm), space velocities of 20,000-60,000 h-1, and H2-to-CO ratios of 3. The reaction is catalyzed by a copper-zinc oxide catalyst using promoters such as alumina. This catalyst is more easily poisoned than the older copper chromite catalysts and requires the use of sulfur-free synthesis gas. The reaction between carbon monoxide and hydrogen is exothermic ... and plants must be designed to remove heat efficiently. In order to control the exotherm, CO conversions are typically maintained well below the equilibrium conversion, 45% at 523 deg K. This necessitates a substantial recycle of carbon monoxide and hydrogen. [Kirk-Othmer Encyclopedia of Chemical Technology. 4th ed. Volumes 1: New York, NY. John Wiley and Sons, 1991-Present., p. V5 103 (1993)] **PEER REVIEWED**

/The liquid-phase methanol/ ... process utilizes a catalyst such as copper -zinc oxide suspended in a hydrocarbon oil. The liquid phase is used as a heat-transfer medium and allows the reaction to be conducted at higher conversions than conventional reactor designs. In addition, the use of the liquid-phase methanol process allows the use of a coal-derived, CO-rich synthesis gas. Typical reactor conditions for this process are 3.5-6.3 MPa (35-60 atm) and 473-563 deg K. [Kirk-Othmer Encyclopedia of Chemical Technology. 4th ed. Volumes 1: New York, NY. John Wiley and Sons, 1991-Present., p. V5 103 (1993)] **PEER REVIEWED**

By high-pressure catalytic synthesis from carbon monoxide and hydrogen; partial oxidation of natural gas hydrocarbons; Several processes for making methanol by gasification of wood, peat and lignite have been developed but have not yet proved out commercially; From methane with molybdenum catalyst (experimental). [Lewis, R.J. Sr.; Hawley's Condensed Chemical Dictionary 14th Edition. John Wiley & Sons, Inc. New York, NY 2001., p. 722] **PEER REVIEWED**

GENERAL MANUFACTURING INFORMATION: Methanol usually is better solvent than ethanol, dissolves many inorganic salts ... sodium iodide 43%, calcium chloride 22%, ammonium nitrate 14%, copper sulfate 13%, silver nitrate 4%, ammonium chloride 3.2%, sodium 

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2/24/2011 htt p ://toxnet.nlm.nih. g ov/c g i- b in/sis/download.txtchloride 1.4%. [O'Neil, M.J. (ed.). The Merck Index - An Encyclopedia of Chemicals, Drugs, and Biologicals. 13th Edition, Whitehouse Station, NJ: Merck and Co., Inc., 2001., p. 1065] **PEER REVIEWED**

METHANOL IS PURIFIED BY DISTILLATION. [Kirk-Othmer Encyclopedia of Chemical Technology. 3rd ed., Volumes 1-26. New York, NY: John Wiley and Sons, 1978-1984., p. 15(78) 408] **PEER REVIEWED**

FORMULATIONS/PREPARATIONS: Grade: Technical, CP (99.85%), electronic (used to clean and dry componets), fuel [Lewis, R.J. Sr.; Hawley's Condensed Chemical Dictionary 14th Edition. John Wiley & Sons, Inc. New York, NY 2001., p. 722]

**PEER REVIEWED**

Formaldehyde; intrastate fungicide; 37.0% formaldehyde, 15.0% methyl alcohol. [Purdue University; National Pesticide Information Retrieval System (1988)] **PEER REVIEWED**

Wilbur-Ellis Smut-Guard; fungicide; 37.0% formaldehyde, 12.0% methyl alcohol. [Purdue University; National Pesticide Information Retrieval System (1988)] **PEER REVIEWED**

Eureka Products, Criosine; intrastate disinfectant/bacteriocide/germicide; 47.6% methyl alcohol, 0.86% nitrobenzene, 0.54% butyl 4-hydroxybenzoate, 30.0% phenol. [Purdue University; National Pesticide Information Retrieval System (1988)] **PEER REVIEWED**

Surflo-B17; microbicide/microbisat general; 32.37% formaldehyde, 10.5% methyl alcohol, 10.0% alkyl dimethyl benzyl ammonium chloride. [Purdue University; National Pesticide Information Retrieval System (1988)] **PEER

REVIEWED**

Coat-B1400; solution ready to use; 25.0% methyl alcohol, 24.0% morpholine polyethoxyethanol. [Purdue University; National Pesticide Information Retrieval System (1988)] **PEER REVIEWED**

Ideal Concentrated Wood Preservative; fungicide; 15.0% isopropanol, 15.0% methyl alcohol, 10.0% orthodichlorobenzene, 38.4% pentachlorophenol, 20.0% aliphatic petroleum hydrocarbons. [Purdue University; National Pesticide Information Retrieval System (1988)] **PEER REVIEWED**

Freer Elm Arrester; fungicide; 0.12% mecuric chloride, 96.65% methyl alcohol. [Purdue University; National Pesticide Information Retrieval System (1988)] **PEER REVIEWED**

Eureka Products Criosine Disinfectant; disinfectant/bacteriocide/germicide; 47.6% methyl alcohol, 0.86% nitrobenzene, 0.54% butyl 4-hydroxybenzoate, 30.0% phenol. [Purdue University; National Pesticide Information Retrieval System (1988)] **PEER

REVIEWED**

X-Cide 402 Industrial Bactericide; bacteriostat; 11.5% isopropanol, 16.4% methyl alcohol, 28.5% alkyl amino-3-aminopropane monoacetate, 17.8% oxydiethylenebis(alkyl) dimethyl ammonium chloride. [Purdue University; National Pesticide Information Retrieval System (1988)] **PEER REVIEWED**

IMPURITIES: GRADE A) ACETONE AND ALDEHYDES 30 PPM MAX; ACETIC ACID 30 PPM MAX: WATER CONTENT 1500 PPM MAX; GRADE AA) ACETONE AND ALDEHYES 30 PPM MAX; ACETONE

20 PPM MAX; ETHANOL 10 PPM MAX; ACETIC ACID 30 PPM MAX; WATER CONTENT 100 PPM MAX. [Kirk-Othmer Encyclopedia of Chemical Technology. 3rd ed., Volumes 1-26. New York, NY: John Wiley and Sons, 1978-1984., p. 15(81) 409] **PEER REVIEWED**

Water, dimethyl ether, fusel oils, and higher alcohols. [Environment Canada; Tech Info for Problem Spills: Methanol (Draft) p.15 (1981)] **PEER

REVIEWED**

CONSUMPTION PATTERNS:

39% FOR FORMALDEHYDE; 12% EXPORTED; 8% FOR SOLVENT USAGE; 6% FOR DIMETHYL

TEREPHTHALATE; 6% FOR METHYL HALIDES; 4% FOR METHYL METHACRYLATE; 3% FOR

ACETIC ACID; 3% FOR METHYLAMINES; 1% FOR FORMALDEHYDE INHIBITOR; 17% MISC (1973) [SRI] **PEER REVIEWED**

CHEMICAL PROFILE: Methanol. Formaldehyde, 27%; MTBE /methyl tert-butyl ether/, 25%; acetic acid, 11%; chloromethanes, 7%; solvents, 8%; methyl halides, 4%; methyl methacrylates, 4%; methylamines, 3%; methylene chloride, 2%; utility power, 1%; miscellaneous and exports, 2%. [Kavaler AR; Chemical Marketing Reporter 230 (12): 70 (1986)] **PEER REVIEWED**

CHEMICAL PROFILE: Methanol. Demand: 1985: 1.29 billion gallons; 1986: 1.35 billion gallons; 1990 /projected/: 1.6 billion gallons. [Kavaler AR; Chemical Marketing Reporter 230 (12): 70 (1986)] **PEER REVIEWED**

CHEMICAL PROFILE: Methanol. Formaldehyde, 27%; MTBE /methyl tert-butyl ether/, 26%; acetic acid, 11%; chloromethanes, 7%; solvents, 7%; methyl halides, 4%; methylmethacrylates, 4%; methylamines, 3%; methylene chloride, 2%; miscellaneous and exports, 9%. [Kavaler AR; Chemical Marketing Reporter 236 (13): 62 (1989)] **PEER REVIEWED**

CHEMICAL PROFILE: Methanol. Demand: 1988: 1.8 billion gallons; 1989: 1.6 

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2/24/2011 htt p ://toxnet.nlm.nih. g ov/c g i- b in/sis/download.txtbillion gallons; 1993 /projected/: 2.2 billion gallons. (Includes imports, which totaled 690 million gallons last year, as well as export shipments, which are negligible, totaling 36 million gallons last year.) [Kavaler AR; Chemical Marketing Reporter 236 (13): 62 (1989)] **PEER REVIEWED**

CHEMICAL PROFILE: Methanol. Demand: 2000: 2.92 billion gallons; 2001: 2.838 billion gallons; 2005 /projected/: 2.7 billion gallons with MTBE phase out or 3.11 billion gallons with MTBE phase out. [Kirshner M; Chemical Marketing Reporter. December, 16 (2002)] **PEER REVIEWED**

U. S. PRODUCTION: This chemical is listed as a High Production Volume (HPV) (65FR81686; http://www.epa.gov/opptintr/chemrtk/hpvchmlt.htm). Chemicals listed as HPV were produced in or imported into the U.S. in > 1 million pounds in 1990. The HPV list is based on the 1990 Inventory Update Rule. (IUR) (40 CFR part 710 subpart B; 51FR21438; http://www.epa.gov/oppt/iur/index.htm). [EPA/Office of Pollution Prevention and Toxics; High Production Volume (HPV) Challenge Program's Robust Summaries and Test Plans. Available from, as of December 19, 2005: http://www.epa.gov/hpv/pubs/general/opptsrch.htm]

**PEER REVIEWED**

(1984) 3.72X10+12 g [USITC. SYN ORG CHEM-U.S. PROD/SALES p.256 (1984)]

**PEER REVIEWED**

5.00X10+9 lb /Synthetic/ [USITC. SYN ORG CHEM-U.S. PROD/SALES p.266 (1985)] **PEER REVIEWED**

(1990) 8.35 billion lb [Chem & Engineering News 70 (15): 17 (4/13/92)]

**PEER REVIEWED**

(1991) 8.71 billion lb [Chem & Engineering News 71 (15): 11 (4/12/93)]

**PEER REVIEWED**

(1992)8.08 billion lb [Chem & Engineering News 72 (15): 13 (4/11/94)]

**PEER REVIEWED**

(1993) 10.54 billion lb [Chem & Engineering News 72 (15): 13 (4/11/94)] **PEER REVIEWED**

(1986) > 1 billion pounds [US EPA; Non-confidential Production Volume Information Submitted by Companies for Chemicals Under the 1986-2002 Inventory Update Rule (IUR). Methanol (67-56-1). Available from, as of July 28, 2005: http://www.epa.gov/oppt/iur/tools/data/2002-vol.html]

**PEER REVIEWED**

(1990) > 1 billion pounds [US EPA; Non-confidential Production Volume Information Submitted by Companies for Chemicals Under the 1986-2002 Inventory Update Rule (IUR). Methanol (67-56-1). Available from, as of July 28, 2005: http://www.epa.gov/oppt/iur/tools/data/2002-vol.html]

**PEER REVIEWED**

(1994) > 1 billion pounds [US EPA; Non-confidential Production Volume Information Submitted by Companies for Chemicals Under the 1986-2002 Inventory Update Rule (IUR). Methanol (67-56-1). Available from, as of July 28, 2005: http://www.epa.gov/oppt/iur/tools/data/2002-vol.html]

**PEER REVIEWED**

(1998) > 1 billion pounds [US EPA; Non-confidential Production Volume Information Submitted by Companies for Chemicals Under the 1986-2002 Inventory Update Rule (IUR). Methanol (67-56-1). Available from, as of July 28, 2005: http://www.epa.gov/oppt/iur/tools/data/2002-vol.html]

**PEER REVIEWED**

(2002) > 1 billion pounds [US EPA; Non-confidential Production Volume Information Submitted by Companies for Chemicals Under the 1986-2002 Inventory Update Rule (IUR). Methanol (67-56-1). Available from, as of July 28, 2005: http://www.epa.gov/oppt/iur/tools/data/2002-vol.html]

**PEER REVIEWED**

U. S. IMPORTS: (1983) 6.74X10+7 g [BUREAU OF THE CENSUS. U.S. IMPORTS FOR CONSUMPTION & GENERAL IMPORTS, p.1-360 (1984)] **PEER REVIEWED**

(1984) 5.13X10+8 g [BUREAU OF THE CENSUS. U.S. IMPORTS FOR CONSUMPTION & GENERAL IMPORTS, p.1-360 (1984)] **PEER REVIEWED**

17.72X10+6 gal /For producing synthetic natural gas (SNG) or for use as fuel/ [BUREAU OF THE CENSUS. US IMPORTS FOR CONSUMPTION AND GENERAL IMPORTS P.1-527 (1986)] **PEER REVIEWED**

3.59X10+8 gal /NSPF/ [BUREAU OF THE CENSUS. US IMPORTS FOR CONSUMPTION AND GENERAL IMPORTS P.1-527 (1986)] **PEER REVIEWED**

1.421 billion gallons in 2000, 1.816 billion gallons in 2001 [Kirshner M; Chemical Marketing Reporter. December 16, (2002)] **PEER REVIEWED**

U. S. EXPORTS: (1984) 1.95X10+10 g [BUREAU OF THE CENSUS. U.S. EXPORTS p.2-75 (1984)]

**PEER REVIEWED**

(1987) 1.2X10+6 gal [BUREAU OF THE CENSUS. U. S. EXPORTS, SCHEDULE E, 

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2/24/2011 htt p ://toxnet.nlm.nih. g ov/c g i- b in/sis/download.txtP.2-76 (OCTOBER 1987)] **PEER REVIEWED**

32 million gallons in 2000, 52 million gallons in 2001 [Kirshner M; Chemical Marketing Reporter. December 16, (2002)]] **PEER REVIEWED**

LABORATORY METHODS:

CLINICAL LABORATORY METHODS: Ultramicro chromatographic method, incl methanol, in blood & urine. [Manno BR, Manno JE; Simple Approach to Gas Chromatographic Microanalysis of Alcohol in Blood & Urine By Direct-Injection Technique; J Anal Tox 2 (6): 257-61 (1978)] **PEER REVIEWED**

... Determination in blood serum of methanol ... was accomplished by gas chromatography using a Varian Model 2100 gas chromatograph equipped with dual columns, dual flame ionization detectors, and a linear temp programmer. Standard curves were linear ... over the concn range 1-100 nmol/ml and the limits of detection were 0.1 nmol/ml ethylene glycol. No interference from 30 solvents studied was detected. [Cheung ST, Lin WN; J Chromatogr 414 (1): 248-50 (1987)] **PEER REVIEWED** <a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=3571391" target=new>PubMed Abstract

A quantitative method for the determination of methanol and formic acid in urine of workers was described. One female and 13 male workers of mean age 41 years exposed to methanol 10 +/5 years, and five female and five male workers exposed to formic acid for 6 +/4 years participated in the study. ... Urinary samples were taken after the shift on Thursdays and on Friday mornings. The time weighted average exposure to methanol ranged from 58 to 277 ug/l. The highest concentrations of urinary formic acid were measured in the samples taken on Friday morning and ranged from 26 to 98 mg/g of creatinine. The output of urinary formic acid 16 hours after exposure was found to be linearly proportional to the methanol concentration in air. No correlations were found between the methanol exposure and the urinary formic acid or methanol concentrations in samples taken immediately after the shift. The time weighted average exposure to formic acid ranged form 4.1 to 11.3 ug/l. The corresponding levels of the urinary formic acid in the Friday samples were 21.2 and 118 mg/g creatinine, respectively. A

linear correlation between the formic acid in the air and in the urine 16 hours after the exposure was observed with the correlation coefficient of 0.88. ... Urinary sampling for formic acid provides a reliable and simple strategy for detection of occupational exposure to methanol and formic acid at current levels found in industry. [Liesivuori J, Savolainen H; Am Ind Hyg Assoc J 48 (1): 32-34 (1987)] **PEER REVIEWED** <a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=3565260" target=new>PubMed Abstract

A study was performed among 20 workers employed in a printing office at 3 different work places (methanol concentration of 85, 101 and 134 ppm) to

determine whether the concentration of formic acid in blood or urine and the methanol content of alveolar air permit the estimation of methanol exposure. Blood, urine and end expiratory air were collected at the beginning and the end of the shift. For comparison formic acid concentrations were determined in the morning and in the afternoon in blood and urine of 36 and 15 control persons, respectively. The concentration of formic acid in blood increased significantly from 3.2:2.4 mg/l before to 7.9:3.2 mg/l after the shift in the exposed workers (mean increase 4.7:3.8 mg/l). The corresponding concentrations in urine were 13.1:5.3 mg/l. This difference is also significant. In the control groups there was a small but significant decrease of formic acid concentration in blood from 5.6:4.5 mg/l in the morning to 4.9:4.2 mg/l in the afternoon. In urine, the formic acid concentrations in the morning (11.9:6.4 mg/l) and in the afternoon (11.7:5.6 mg/l) were not significantly different. The increase of formic acid concentration in blood during the shift is the most useful parameter for monitoring methanol-exposed persons.

Determinations of methanol concentrations in the ambient air or in the exhaled air are only crude estimates. [Baumann K, Angerer J; Int Arch Occup Environ Health 42 (3-4): 241-9 (1979)] **PEER REVIEWED** <a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=422265" target=new>PubMed Abstract

ANALYTIC LABORATORY METHODS: Method: NIOSH 2000; Procedure: Gas chromatography with flame ionization detector; Analyte: methanol; Matrix: air; Detection Limit: 0.7 ug per sample. [CDC; NIOSH Manual of Analytical Methods, 4th ed. Methanol (67-56-1). Available from, as of June 1, 2005: http://www.cdc.gov/niosh/docs/2003-154/] **PEER REVIEWED**

Method: NIOSH 2549, Volatile Organic Compounds (Screening); Procedure: Thermal desorption, gas chromatography, mass spectrometry; Analyte: methanol; Matrix: air; Detection Limit: 100 ng per tube or less. [CDC; NIOSH Manual of Analytical Methods, 4th ed. Methanol (67-56-1). Available from, as of June 1, 2005: http://www.cdc.gov/niosh/docs/2003-154/] **PEER

REVIEWED**

Method: OSHA 91: Procedure: Gas chromatography with flame ionization detector; Analyte: methanol; Matrix: air; Detection Limit: 142 ppb (186 ug/cu m). [U.S. Department of Labor/Occupational Safety and Health Administration's Index of Sampling and Analytical Methods. Available 

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2/24/2011 htt p ://toxnet.nlm.nih. g ov/c g i- b in/sis/download.txtfrom: http://www.osha.gov/dts/sltc/methods/toc.html on Methanol (67-56-1) as of June 1, 2005] **PEER REVIEWED**

Method: AOAC 972.11, Methanol in Distilled Liquors; Procedure: Gas chromatographic method; Analyte: methanol; Matrix: distilled liquors; Detection Limit: not provided. [Horwitz W, ed.; Official Methods of Analysis of AOAC International 17th ed. (2003). CD-ROM, AOAC International, Gaithersburg, MD] **PEER REVIEWED**

Method: AOAC 971.03, Methanol in Hazardous Substances; Procedure: Gas chromatography with flame ionization detector; Analyte: methanol; Matrix: applicable in presence of acetone, butyl acetate, ethyl alcohol, isopropanol, hexane, methyl ethyl ketone, CH2Cl2, 2-methoxyethanol, paraffin, toluene, and H2O, including many paint removers, fuels, liquid sanders, antifreezes, and paint products; Detection Limit: not provided. [Horwitz W, ed.; Official Methods of Analysis of AOAC International 17th ed. (2003). CD-ROM, AOAC International, Gaithersburg, MD] **PEER

REVIEWED**

Method: AOAC 958.04, Methanol in Distilled Liquors; Procedure: Chromotropic acid colorimetric method; Analyte: methanol; Matrix: distilled liquors; Detection Limit: not provided. [Horwitz W, ed.; Official Methods of Analysis of AOAC International 17th ed. (2003). CD-ROM, AOAC International, Gaithersburg, MD] **PEER REVIEWED**

Method: AOAC 920.132; Methanol in Vanilla Extract; Procedure: Titrimetric method; Analyte: methanol; Matrix: vanilla extract; Detection Limit: not provided. [Horwitz W, ed.; Official Methods of Analysis of AOAC International 17th ed. (2003). CD-ROM, AOAC International, Gaithersburg, MD] **PEER REVIEWED**

Method: EPA-OSW 8015C; Procedure: Nonhalogenated Organics by GC-FID; Analyte: methanol; Matrix: surface water, ground water, and solid matrices; Detection Limit: 21 ug/L. [National Environmental Methods Index; Analytical, Test and Sampling Methods. Methanol (67-56-1). Available from, as of June 1, 2005: http://www.nemi.gov] **PEER REVIEWED**

Method: EPA-OSW 8260B; Procedure: Volatile Organic Compounds by GC/MS; Analyte: methanol; Matrix: determines most volatile organic compounds with boiling points below 200 C; Detection Limit: not provided. [National Environmental Methods Index; Analytical, Test and Sampling Methods. Methanol (67-56-1). Available from, as of June 1, 2005: http://www.nemi.gov] **PEER REVIEWED**

SAMPLING PROCEDURES: A known volume of air is drawn through a 7 cm x 6 mm OD silica gel tube containing 2 sections of 20/40 mesh silica gel separated by a 2 mm portion of urethane foam. The first section contains 100 mg whereas the second section contains 50 mg. A silylated glass wool plug is placed before the front absorbing section. A sample size of 5 l of air sampled at 200 ml/min is recommended. The silica gel tube sample is scored before the first section of silica gel and broken. The larger section of silica gel is transferred to a 2 ml stoppered sample container containing 1.0 ml of distilled water. The same operation is performed with the back-up section. The sample should be allowed to desorb for 4 hours. A 5 ul aliquot of sample is injected into a gas chromatograph equipped with a flame ionization detector. [Environment Canada; Tech Info for Problem Spills: Methanol (Draft) p.105-6 (1981)] **PEER REVIEWED**

Qualitative method for the detection of methanol in soil: Acetyl chloride (three to four drops) is placed in a dry test tube and the fumes resulting from the reaction with atmospheric moisture are allowed to dissipate. The sample is added to the test tube dropwise until a total of three drops have been added. A positive indication is given by a vigorous reaction, the mixture boils spontaneously, ... and hydrogen chloride gas is evolved. [Environment Canada; Tech Info for Problem Spills: Methanol (Draft) p.108 (1981)] **PEER REVIEWED**

A sampling system designed to quantify compounds in a mixture of polar and non-polar organic vapors was tested. Employees in a motor manufacturing facility who were exposed to mixtures containing toluene, xylene, butanol, ethanol, isopropanol, and methanol were studied. A personal sampling pump

with two charcoal tubes in series was used. The second tube was used to collect vapors that passed through the first tube because of overloading or selective displacement. Desorption efficiency was determined. Non-polar compounds, toluene and xylene, were collected effectively by the first tube until overload. When vapor concentrations were low, almost all non-polar compounds were collected in the first tube. The percent of polar compounds collected in the first tube was about 97%. Ethanol was not collected effectively. A moderate increase in concentration caused vapors to pass to the second tube. An increase in other polar compounds caused ethanol to be displaced. Collection efficiency was poor in the first tube when the concentrations of all vapors was high. ... Silica gel /could/ be used as a collection medium in the back up or second tube when mixtures contain both polar and non-polar vapors. [Goller JW; Am Ind Hyg Assoc J 46 (3): 170-73 (1985)] **PEER REVIEWED**

Two sampling methods for reliable determination of methanol concentration were studied. Methanol vapor stored in glass container was found to be decomposed on the glass surface. The decomposition increased as the surface area of the glass container was extended. The proportion of the 

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2/24/2011 htt p ://toxnet.nlm.nih. g ov/c g i- b in/sis/download.txtdecomposition in the glass container was relatively high, especially when the concentration of methanol vapor was low. Therefore, a reliable determination by the above sampling method was impossible. In the solid sorbent sampling by silica gel, the collected methanol was also decomposed, but the decomposed amount was negligibly small compared to the

collected methanol when the amount of methanol was more than 0.1 of the liquid methanol. It could be concluded from the foregoing findings that the determination of methanol concentration by this method is reliable. [Niisawa K et al; Sangyo Igaku 28 (3): 177-80 (1986)] **PEER REVIEWED** <a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=3773296" target=new>PubMed Abstract

A new method is described for collecting and concentrating volatile compounds in the breath, in order to facilitate their assay by gas chromatography. Breath was collected into sealed Mylar bags containing an internal standard (isopropyl alcohol). The sample was pumped through a cooled gas chromatograph column, where the volatile compounds were concentrated by adsorption onto the resin packing (Porapak Q) at 35 deg C. The column was then heated, and the volatilized sample was separated for assay by flame ionization detection. ... This assay provided a number of advantages over previously described methods. The use of breath collection bags enabled the collection of samples outside the laboratory. The use of an internal standard in the collection bag reduced errors that might have resulted from leakage of the specimen. An on-column concentration of the sample in the gas chromatograph eliminated the need for an additional preconcentration device, such as cryogenic or adsorptive trapping apparatus. [Phillips M, Greenberg J; Anal Biochem 163 (1): 165-69 (1987)]

**PEER REVIEWED** <a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=3619015" target=new>PubMed Abstract

SPECIAL REFERENCES:

SPECIAL REPORTS: Environment Canada; Tech Info for Problem Spills: Methanol (Draft) (1981)

NIOSH; Criteria Document: Methyl Alcohol (1976) DHEW Pub. NIOSH 76-148

NIOSH; Canadian Centre for Occupational Health and Safety: Chemical Hazard Summary No.24 1986. The chemical hazards, uses, occurrences and toxicological properties of methanol are discussed. ...

DHHS/NTP; NTP-CERHR Expert Panel Report on the Reproductive and Developmental Toxicity of Methanol p.14 (April 2002) NTP-CERHR-MeOH-02.

Available from: http://cerhr.niehs.nih.gov/news/methanol/methanol_final.pdf as of July 20,

2005.

WHO; Environ Health Criteria 196: Methanol p.93 (1997). Available from: http://www.inchem.org/documents/ehc/ehc/ehc196.htm as of July 18, 2005.

European Chemicals Bureau; IUCLID Dataset, Methanol (67-56-1) (2000 CD-ROM edition). Available from the database query page: http://ecb.jrc.it/esis/esis.php as of July 15, 2005.

SYNONYMS AND IDENTIFIERS:

RELATED HSDB RECORDS: 1646 [FORMIC ACID] (metabolite)

164 [FORMALDEHYDE] (metabolic precursor)

3915 [ASPARTAME] (metabolic precursor)

SYNONYMS: Coat-B1400 [Purdue University; National Pesticide Information Retrieval System (1988)] **PEER REVIEWED**

Surflo-B17 [Purdue University; National Pesticide Information Retrieval System (1988)] **PEER REVIEWED**

AI3-00409 **PEER REVIEWED**

Alcohol, methyl **PEER REVIEWED**

ALCOOL METHYLIQUE (FRENCH) [Lewis, R.J. Sax's Dangerous Properties of Industrial Materials. 9th ed. Volumes 1-3. New York, NY: Van Nostrand Reinhold, 1996., p. 2174] **PEER REVIEWED**

ALCOOL METILICO (ITALIAN) [Lewis, R.J. Sax's Dangerous Properties of Industrial Materials. 9th ed. Volumes 1-3. New York, NY: Van Nostrand Reinhold, 1996., p. 2174] **PEER REVIEWED**

CARBINOL [Lewis, R.J. Sax's Dangerous Properties of Industrial Materials. 9th ed. Volumes 1-3. New York, NY: Van Nostrand Reinhold, 1996., p. 2174]

**PEER REVIEWED** 

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2/24/2011 htt p ://toxnet.nlm.nih. g ov/c g i- b in/sis/download.txtCaswell no 552 **PEER REVIEWED**

X-Cide 402 Industrial Bactericide [Purdue University; National Pesticide Information Retrieval System (1988)] **PEER REVIEWED**

COLONIAL SPIRIT [Lewis, R.J. Sax's Dangerous Properties of Industrial Materials. 9th ed. Volumes 1-3. New York, NY: Van Nostrand Reinhold, 1996., p. 2174] **PEER REVIEWED**

COLUMBIAN SPIRITS [Lewis, R.J. Sax's Dangerous Properties of Industrial Materials. 9th ed. Volumes 1-3. New York, NY: Van Nostrand Reinhold, 1996., p. 2174] **PEER REVIEWED**

Ideal Concentrated Wood Preservative [Purdue University; National Pesticide Information Retrieval System (1988)] **PEER REVIEWED**

Wilbur-Ellis Smut-Guard [Purdue University; National Pesticide Information Retrieval System (1988)] **PEER REVIEWED**

Freers Elm Arrester [Purdue University; National Pesticide Information Retrieval System (1988)] **PEER REVIEWED**

Manhattan spirits [WHO; Environ Health Criteria 196: Methanol p.10 (1997). Available from, as of July 14, 2005: http://www.inchem.org/documents/ehc/ehc/ehc196.htm]

METANOLO (ITALIAN) [Lewis, R.J. Sax's Dangerous Properties of Industrial Materials. 9th ed. Volumes 1-3. New York, NY: Van Nostrand Reinhold, 1996., p. 2174] **PEER REVIEWED**

Metanol (Spanish) **PEER REVIEWED**

Methilic alcohol [European Chemicals Bureau; IUCLID Dataset, Methanol (67-56-1) (2000 CD-ROM edition). Available from, as of July 15, 2005: http://ecb.jrc.ec.europa.eu/esis/]

METHYL ALCOHOL [Weast, R.C. (ed.) Handbook of Chemistry and Physics. 69th ed. Boca Raton, FL: CRC Press Inc., 1988-1989., p. C-351] **PEER

REVIEWED**

METHYLALKOHOL (GERMAN) [Lewis, R.J. Sax's Dangerous Properties of Industrial Materials. 9th ed. Volumes 1-3. New York, NY: Van Nostrand Reinhold, 1996., p. 2174] **PEER REVIEWED**

Methyl hydrid [European Chemicals Bureau; IUCLID Dataset, Methanol (67-56-1) (2000 CD-ROM edition). Available from, as of July 15, 2005: http://ecb.jrc.ec.europa.eu/esis/] **PEER REVIEWED**

Methyl hydrate [European Chemicals Bureau; IUCLID Dataset, Methanol (67-56-1) (2000 CD-ROM edition). Available from, as of July 15, 2005: http://ecb.jrc.ec.europa.eu/esis/] **PEER REVIEWED**

METHYL HYDROXIDE [Lewis, R.J. Sax's Dangerous Properties of Industrial Materials. 9th ed. Volumes 1-3. New York, NY: Van Nostrand Reinhold, 1996., p. 2174] **PEER REVIEWED**

METHYLOL [Lewis, R.J. Sax's Dangerous Properties of Industrial Materials. 9th ed. Volumes 1-3. New York, NY: Van Nostrand Reinhold, 1996., p. 2174]

**PEER REVIEWED**

METYLOWY ALKOHOL (POLISH) [Lewis, R.J. Sax's Dangerous Properties of Industrial Materials. 9th ed. Volumes 1-3. New York, NY: Van Nostrand Reinhold, 1996., p. 2174] **PEER REVIEWED**

MONOHYDROXYMETHANE [Lewis, R.J. Sax's Dangerous Properties of Industrial Materials. 9th ed. Volumes 1-3. New York, NY: Van Nostrand Reinhold, 1996., p. 2174] **PEER REVIEWED**

Eureka Products, Criosine [Purdue University; National Pesticide Information Retrieval System (1988)] **PEER REVIEWED**

Eureka Products Criosine Disinfectant [Purdue University; National Pesticide Information Retrieval System (1988)] **PEER REVIEWED**

PYROXYLIC SPIRIT [Lewis, R.J. Sax's Dangerous Properties of Industrial Materials. 9th ed. Volumes 1-3. New York, NY: Van Nostrand Reinhold, 1996., p. 2174] **PEER REVIEWED**

WOOD ALCOHOL [Lewis, R.J. Sax's Dangerous Properties of Industrial Materials. 9th ed. Volumes 1-3. New York, NY: Van Nostrand Reinhold, 1996., p. 2174] **PEER REVIEWED**

WOOD NAPHTHA [Lewis, R.J. Sax's Dangerous Properties of Industrial Materials. 9th ed. Volumes 1-3. New York, NY: Van Nostrand Reinhold, 1996., p. 2174] **PEER REVIEWED**

WOOD SPIRIT [Lewis, R.J. Sax's Dangerous Properties of Industrial Materials. 9th ed. Volumes 1-3. New York, NY: Van Nostrand Reinhold, 1996., p. 2174] **PEER REVIEWED**

USEPA/OPP Pesticide Code: 053801 [U.S. Environmental Protection 

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2/24/2011 htt p ://toxnet.nlm.nih. g ov/c g i- b in/sis/download.txtAgency/Office of Pesticide Program's Chemical Ingredients Database on Methanol (67-56-1). Available from, as of June 1, 2005: http://ppis.ceris.purdue.edu/htbin/epachem.com] **PEER REVIEWED**

FORMULATIONS/PREPARATIONS: Grade: Technical, CP (99.85%), electronic (used to clean and dry componets), fuel [Lewis, R.J. Sr.; Hawley's Condensed Chemical Dictionary 14th Edition. John Wiley & Sons, Inc. New York, NY 2001., p. 722]

**PEER REVIEWED**

Formaldehyde; intrastate fungicide; 37.0% formaldehyde, 15.0% methyl alcohol. [Purdue University; National Pesticide Information Retrieval System (1988)] **PEER REVIEWED**

Wilbur-Ellis Smut-Guard; fungicide; 37.0% formaldehyde, 12.0% methyl alcohol. [Purdue University; National Pesticide Information Retrieval System (1988)] **PEER REVIEWED**

Eureka Products, Criosine; intrastate disinfectant/bacteriocide/germicide; 47.6% methyl alcohol, 0.86% nitrobenzene, 0.54% butyl 4-hydroxybenzoate, 30.0% phenol. [Purdue University; National Pesticide Information Retrieval System (1988)] **PEER REVIEWED**

Surflo-B17; microbicide/microbisat general; 32.37% formaldehyde, 10.5% methyl alcohol, 10.0% alkyl dimethyl benzyl ammonium chloride. [Purdue University; National Pesticide Information Retrieval System (1988)] **PEER

REVIEWED**

Coat-B1400; solution ready to use; 25.0% methyl alcohol, 24.0% morpholine polyethoxyethanol. [Purdue University; National Pesticide Information Retrieval System (1988)] **PEER REVIEWED**

Ideal Concentrated Wood Preservative; fungicide; 15.0% isopropanol, 15.0% methyl alcohol, 10.0% orthodichlorobenzene, 38.4% pentachlorophenol, 20.0% aliphatic petroleum hydrocarbons. [Purdue University; National Pesticide Information Retrieval System (1988)] **PEER REVIEWED**

Freer Elm Arrester; fungicide; 0.12% mecuric chloride, 96.65% methyl alcohol. [Purdue University; National Pesticide Information Retrieval System (1988)] **PEER REVIEWED**

Eureka Products Criosine Disinfectant; disinfectant/bacteriocide/germicide; 47.6% methyl alcohol, 0.86% nitrobenzene, 0.54% butyl 4-hydroxybenzoate, 30.0% phenol. [Purdue University; National Pesticide Information Retrieval System (1988)] **PEER

REVIEWED**

X-Cide 402 Industrial Bactericide; bacteriostat; 11.5% isopropanol, 16.4% methyl alcohol, 28.5% alkyl amino-3-aminopropane monoacetate, 17.8% oxydiethylenebis(alkyl) dimethyl ammonium chloride. [Purdue University; National Pesticide Information Retrieval System (1988)] **PEER REVIEWED**

SHIPPING NAME/ NUMBER DOT/UN/NA/IMO:

UN 1230; Methanol

IMO 3.2; Methanol

STANDARD TRANSPORTATION NUMBER: 49 092 30; Methanol or methyl alcohol (wood alcohol)

49 092 37; Methanol (contaminated, only for refining)

49 104 04; Methanol, solidified (alcohol, not otherwise specified)

EPA HAZARDOUS WASTE NUMBER: U154; A toxic waste when a discarded commercial chemical product or manufacturing chemical intermediate or an off-specification commercial chemical product.

F003; A hazardous waste from nonspecific sources when a spent solvent.

ADMINISTRATIVE INFORMATION:

HAZARDOUS SUBSTANCES DATABANK NUMBER: 93

LAST REVISION DATE: 20060414

LAST REVIEW DATE: Reviewed by SRP on 9/15/2005

UPDATE HISTORY: Field Update on 2010-06-02, 4 fields added/edited/deleted

Field Update on 2010-04-27, 1 fields added/edited/deleted

Field Update on 2008-09-02, 2 fields added/edited/deleted

Field Update on 2008-08-15, 25 fields added/edited/deleted

Field Update on 2007-06-07, 1 fields added/edited/deleted 

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2/24/2011 htt p ://toxnet.nlm.nih. g ov/c g i- b in/sis/download.txtField Update on 2006-04-18, 2 fields added/edited/deleted

Field Update on 2006-04-17, 2 fields added/edited/deleted

Complete Update on 2006-04-14, 84 fields added/edited/deleted

Complete Update on 2005-06-24, 20 fields added/edited/deleted

Field Update on 2005-01-27, 2 fields added/edited/deleted

Complete Update on 02/14/2003, 1 field added/edited/deleted.

Complete Update on 11/08/2002, 1 field added/edited/deleted.

Complete Update on 10/31/2002, 1 field added/edited/deleted.

Complete Update on 07/22/2002, 1 field added/edited/deleted.

Complete Update on 05/13/2002, 1 field added/edited/deleted.

Complete Update on 01/18/2002, 4 fields added/edited/deleted.

Field Update on 01/14/2002, 1 field added/edited/deleted.

Complete Update on 08/09/2001, 1 field added/edited/deleted.

Complete Update on 05/16/2001, 1 field added/edited/deleted.

Complete Update on 05/15/2001, 1 field added/edited/deleted.

Complete Update on 02/22/2001, 2 fields added/edited/deleted.

Complete Update on 02/08/2000, 1 field added/edited/deleted.

Complete Update on 02/02/2000, 1 field added/edited/deleted.

Complete Update on 11/18/1999, 1 field added/edited/deleted.

Complete Update on 09/27/1999, 1 field added/edited/deleted.

Complete Update on 09/21/1999, 1 field added/edited/deleted.

Complete Update on 08/26/1999, 1 field added/edited/deleted.

Complete Update on 07/20/1999, 5 fields added/edited/deleted.

Complete Update on 05/04/1999, 1 field added/edited/deleted.

Complete Update on 03/29/1999, 3 fields added/edited/deleted.

Field Update on 03/19/1999, 1 field added/edited/deleted.

Field Update on 03/19/1999, 1 field added/edited/deleted.

Complete Update on 03/01/1999, 1 field added/edited/deleted.

Complete Update on 01/20/1999, 1 field added/edited/deleted.

Complete Update on 11/12/1998, 2 fields added/edited/deleted.

Field Update on 10/29/1998, 1 field added/edited/deleted.

Complete Update on 09/11/1998, 1 field added/edited/deleted.

Complete Update on 06/02/1998, 1 field added/edited/deleted.

Complete Update on 02/25/1998, 1 field added/edited/deleted.

Complete Update on 10/17/1997, 1 field added/edited/deleted.

Complete Update on 08/13/1997, 1 field added/edited/deleted.

Complete Update on 05/08/1997, 1 field added/edited/deleted.

Complete Update on 03/27/1997, 2 fields added/edited/deleted.

Complete Update on 02/24/1997, 1 field added/edited/deleted.

Complete Update on 10/12/1996, 1 field added/edited/deleted.

Complete Update on 07/22/1996, 5 fields added/edited/deleted.

Complete Update on 06/03/1996, 1 field added/edited/deleted.

Complete Update on 05/10/1996, 1 field added/edited/deleted.

Complete Update on 04/16/1996, 8 fields added/edited/deleted.

Field Update on 01/18/1996, 1 field added/edited/deleted. 

# Iris Camacho, 6308MM Pa g e 68 of 69

2/24/2011 htt p ://toxnet.nlm.nih. g ov/c g i- b in/sis/download.txtComplete Update on 05/26/1995, 1 field added/edited/deleted.

Complete Update on 01/23/1995, 1 field added/edited/deleted.

Complete Update on 12/19/1994, 1 field added/edited/deleted.

Complete Update on 11/18/1994, 1 field added/edited/deleted.

Complete Update on 07/28/1994, 1 field added/edited/deleted.

Complete Update on 06/08/1994, 1 field added/edited/deleted.

Complete Update on 03/25/1994, 1 field added/edited/deleted.

Complete Update on 08/07/1993, 1 field added/edited/deleted.

Complete Update on 08/04/1993, 1 field added/edited/deleted.

Complete Update on 04/28/1993, 2 fields added/edited/deleted.

Complete Update on 02/05/1993, 1 field added/edited/deleted.

Field update on 12/10/1992, 1 field added/edited/deleted.

Complete Update on 11/26/1992, 1 field added/edited/deleted.

Complete Update on 09/03/1992, 1 field added/edited/deleted.

Complete Update on 05/29/1992, 1 field added/edited/deleted.

Complete Update on 04/27/1992, 1 field added/edited/deleted.

Complete Update on 01/23/1992, 1 field added/edited/deleted.

Field update on 01/28/1991, 1 field added/edited/deleted.

Complete Update on 10/10/1990, 1 field added/edited/deleted.

Complete Update on 05/21/1990, 1 field added/edited/deleted.

Complete Update on 05/04/1990, 1 field added/edited/deleted.

Complete Update on 01/11/1990, 2 fields added/edited/deleted.

Complete Update on 08/17/1989, 103 fields added/edited/deleted.

Field Update on 07/06/1988, 1 fields added/edited/deleted.

Field Update on 07/06/1988, 1 fields added/edited/deleted.

Complete Update on 06/04/1985

Created 19830401 by GCF 

# Iris Camacho, 6308MM Pa g e 69 of 69

2/24/2011 htt p ://toxnet.nlm.nih. g ov/c g i- b in/sis/download.txt