Toxnet

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 December 19, 2015.
Query: Records containing the term 93
1 - HSDB
NAME: METHANOL
HSN: 93
RN: 67-56-1
OVERVIEW:
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
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**
HUMAN TOXICITY EXCERPTS:
/HUMAN EXPOSURE STUDIES/ ... An examination of 12 fatalities attributed to
methanol poisoning is presented. Six individuals were found deceased, and
their postmortem methanol and formic acid concentrations ranged from 84 to
543 mg/dL and 64 to 110 mg/dL, respectively. In the other six individuals,
hospital treatment such as bicarbonate, ethanol infusion, and hemodialysis
was administered. Antemortem methanol and formic acid concentrations
ranged from 68 to 427 mg/dL and 37 to 91 mg/dL, respectively, whereas
corresponding postmortem methanol and formic acid levels ranged from
undetectable to 49 mg/dL and undetectable to 48 mg/dL, respectively.

Hospital treatment of formic acid toxicity resulted in significantly
reduced postmortem methanol and formic acid concentrations. ...[Wallage
HR, Watterson JH; J Anal Toxicol. 32 (3): 241-7 (2008)] **PEER REVIEWED**
<a href="http://www.ncbi.nlm.nih.gov/pubmed/18397576?dopt=Abstract"
target=new>PubMed Abstract
/HUMAN EXPOSURE STUDIES/ ... CT and MR findings in nine patients
following an outbreak of methanol poisoning. Five patients with a typical
clinical presentation and elevated anion and osmolar gaps underwent
conventional brain MRI with a 1.5-T Gyroscan Interna scanner. In addition
nonenhanced CT was performed in another three patients with more severe
toxicity. Bilateral hemorrhagic or nonhemorrhagic necrosis of the
putamina, diffuse white matter necrosis, and subarachnoid hemorrhage were
among the radiological findings. Various patterns of enhancement of basal
ganglial lesions were found including no enhancement, strong enhancement
and rim enhancement.[Sefidbakht S et al; Neuroradiology. 49 (5): 427-35
(2007)] **PEER REVIEWED** <a
href="http://www.ncbi.nlm.nih.gov/pubmed/17294234?dopt=Abstract"
/HUMAN EXPOSURE STUDIES/ ... /Glial fibrillary acidic protein (GFAP) and
/antigen/ CD34 were immunohistochemically localized in the post-mortem
optic nerve head, and brain tissue (basal ganglia putamen) samples were
collected from methanol-exposed and non-methanol-exposed (control) /human/
subjects. There was a positive correlation between the GFAP and CD34
intensity of staining scores in the methanol-exposed group (P=0.711,
P=0.010). Furthermore, there was also a positive correlation between the
brain putamen and optic nerve head GFAP extent of staining in the
methanol-exposed group (P=0.720, P=0.008). A statistically significant
difference was found between the methanol-exposed group and the control
group optic nerve CD34 intensity scores (P=0.014), but no significant
difference was found between optic nerve CD34 and GFAP extent scores
(P=0.05). The study revealed that methanol affects brain putamen and the
optic nerve selectively. /Researchers/ detected a positive significant
correlation between brain and optic nerve GFAP expression. CD34 expression
was markedly decreased by the toxic effects of methanol.[Turkmen N et al;
Adv Ther. 25 (2): 123-32 (2008)] **PEER REVIEWED** <a
/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.;
/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
the 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:
/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
mM/L) or a high anion gap metabolic acidosis. Indications for hemodialysis
were: blood methanol concentration > 50 mg/dL (15.8 mM/L), metabolic
acidosis (bicarbonate < 15 mM/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
/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 uM/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
/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 mM/L (13.3 mg/dL) (range 0 to 87.5 mM/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 mM/L ( <
50 mg/dL). Eight patients [16% (95% CI 8-30%)] had at least one serum
glucose concentration between 2.78-3.61 mM/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 >
3.61mM/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 mM/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
/SIGNS AND SYMPTOMS/ ... Oxalate crystal deposition likely causes the
cranial neuropathies related to ethylene glycol and 2-hydroxyethoxyacetic
acid is thought to be the causal moiety in cranial neuropathies resulting
from diethylene glycol toxicity. Formic acid is implicated in the optic
nerve damage associated with methanol. Uncommonly, delayed neurological
syndromes may develop as complications of poisoning due to ethylene
glycol, diethylene glycol and methanol; the onset of such neurological
damage is often days or even weeks post-ingestion. ...[Reddy NJ et al;
Clin Toxicol (Phila). 48 (10): 967-73 (2010)] **PEER REVIEWED** <a
/SIGNS AND SYMPTOMS/ SYMPTOMATOLOGY: A latency usually of 12-18 hours,
during which time the only clinical signs are those of a generally mild
and 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] **PEER REVIEWED**
/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
REVIEWED**
/SIGNS AND SYMPTOMS/ Acute methanol toxicity in humans is characterized
in a well-defined pattern. Depending on the amount consumed, a narcotic
effect 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.;
/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:
/SIGNS AND SYMPTOMS/ ...A high frequency rate of /disseminated
intravascular coagulation/ -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 REVIEWED**
/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**
/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/ ... A 4 year-old girl was admitted to the emergency
department with her parents with gastrointestinal symptoms; nausea,
vomiting and abdominal pain. Toxicological studies revealed 79 mg/dl blood
level of methanol. ...[Turkmen N et al; Acta Medica (Hradec Kralove). 52
(3): 125-7 (2009)] **PEER REVIEWED** <a
/CASE REPORTS/ ... A 47-year-old-man was found in a public park, acting
intoxicated. A breath analyzer test (Intoxilyzer 5000EN) measured 0.288
g/210 L breath ethanol, without an interferent noted. In the emergency
department, the patient admitted to drinking HEET Gas-Line antifreeze,
which contains 99% methanol. Two to three hours after ingestion, serum and
urine toxicology screen results were negative for ethanol and multiple
other substances. His serum methanol concentration was 589 mg/dL, serum
osmolality 503 mOsm/kg, osmolar gap 193 mOsm/kg, and anion gap 17 mmol/L.
The patient was treated with intravenous ethanol, fomepizole, and
hemodialysis without complication. ...[Caravati EM, Anderson KT; Ann Emerg
Med. 55 (2): 198-200 (2010)] **PEER REVIEWED** <a
/CASE REPORTS/ ... Mass poisoning involving 372 men who had consumed a
soln of 82% methanol and 18% isopropanol /was reported/.[O'Donoghue, J.L.
(ed.). Neurotoxicity of Industrial and Commercial Chemicals. Volume II.
Boca Raton, FL: CRC Press, Inc., 1985., p. 82] **PEER REVIEWED**
/CASE REPORTS/ ... A 37-year-old man who drank industrial alcohol (100
mL/day) for 4 days /was examined with optical coherence tomography (OCT)/.
The retinal profiles were evaluated by OCT and fluorescein angiography
during the course of treatment. OCT demonstrated peripapillary nerve fiber
swelling and accumulation of intraretinal fluid in the acute phase. In the
chronic phase, the retinal thickness was diffusely decreased. Steroid
pulse therapy was not effective, and his visual acuity was 6/200 OD and
4/100 OS 2 years after the event. ...[Fujihara M et al; Jpn J Ophthalmol.
50 (3): 239-41 (2006)] **PEER REVIEWED** <a
/CASE REPORTS/ ... A 37-year-old chronic alcohol abuser with methanol
poisoning, who developed hematuria and upper gastrointestinal (GI)
bleeding after hemodialysis. The upper GI endoscopic findings showed only
low grade esophageal ulceration. Hematuria and upper GI bleeding in our
patient might also have been cause by the effect of heparinization during
hemodialysis.[Mostafazadeh B et al; BMJ Case Rep. 2008;2008:bcr0820080619
(Epub November 2008)] **PEER REVIEWED** <a
target=new>PubMed Abstract Full text: <a
href='https://www.ncbi.nlm.nih.gov/pmc/?term=PMC3124749'
target=new>PMC3124749
/CASE REPORTS/ Retrospective chart review of adults with positive serum
volatile screen for methanol and history of carburetor cleaning fluid fume
inhalation. Sixteen patients were admitted 68 times. Eleven Native
American patients accounted for 90% of admissions. Sixty-five cases
presented with nausea/vomiting; 27 with intoxication or altered mental
status; 21 with specific visual complaints. About 93% had a pH < 7.35,
96% had serum bicarbonate < 20 mEq/L, 81% had osmolal gap > or=10
mOsm/L, and 69% had anion gap > 16. Ten had an initial serum methanol
level < 20 mg/dL, 29 cases 20-49 mg/dL, 19 cases > or=50 mg/dL. Six
patients had a measurable serum ethanol level. Of the 29 patients with a
methanol level of 20-49 mg/dL, 20 received intravenous antidote (ethanol
or fomepizole); three received an antidote and hemodialysis. All who
presented with a serum methanol level > or=50 mg/dL received intravenous
ethanol or fomepizole. All visual symptoms resolved before discharge and
all patients survived without sequelae. ...[Wallace EA, Green AS; Clin
Toxicol (Phila). 47 (3): 239-42 (2009)] **PEER REVIEWED** <a
/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 mM/L (11.8-42.2), arterial pH
7.34 (7.11-7.51), and bicarbonate 17.5 mM/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
/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
/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
/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/pubmed/9296298?dopt=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
/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
REVIEWED**
/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
/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]
**PEER REVIEWED**
/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**
/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
/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).
/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).
/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
/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
/CASE REPORTS/ ...A 28-yr-old pregnant woman /estimated gestational age/
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. During 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

/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
/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 mM/L), formate 14.3 mM/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
/EPIDEMIOLOGY STUDIES/ ... A prospective cross-sectional study in
methanol-poisoned patients in Loghman-Hakim hospital poison center during
9 months from October 1999-June 2000. During this time 25
methanol-poisoned patients were admitted. The mortality rate was 12 (48%).
Amongst survivors, three (23%) of the patients developed blindness due to
their poisoning and the other 10 (77%) fully recovered without any
complication. The mortality rate in comatose patients was nine (90%) while
in non-comatose patients it was three (20%) (P < 0.001). There was a
significant difference in mean pH in the first arterial blood gas of

patients who subsequently died (6.82+/-0.03) and survivors (7.15+/-0.06)
(P < 0.001, M-W). The mean time interval between poisoning and /emergency
department/ presentation in deceased patients were (46+/-15.7) hours, in
survived with sequelae were (16.7+/-6.7) and in survived without sequelae
were (10.3+/-7.2) hours (P < 0.002, K-W). ... No significant difference
between the survivors versus the patients who died regarding methanol.
Simultaneous presence of ethanol and opium affected the outcome of the
treatment for methanol intoxication favourably and unfavourably,
respectively. ... Poor prognosis was associated with pH < 7, coma on
admission and > 24 hours delay from intake to
admission.[Hassanian-Moghaddam H; Hum Exp Toxicol. 26 (7): 583-6 (2007)]
**PEER REVIEWED** <a
/EPIDEMIOLOGY STUDIES/ This cohort study involved 42 consecutive patients
with acute methanol intoxication. Inclusion criteria were consisted of
characteristic clinical presentation of methanol poisoning, and metabolic
acidosis with increased anion and osmolar gaps. Brain /computed
tomography/ (CT) scans without contrast medium were obtained. To determine
the association between the CT findings and death, the chi-square test or
the Fisher's exact test, odds ratio (OR) and its 95% confidence interval
(95% CI) were calculated. Twenty-eight patients (66.6%) had a total of 55
abnormal findings on brain CT, in which bilateral putaminal hypodense
lesions was the most common manifestation (27 cases, 96.4%). Putaminal
hemorrhage with varying degrees was observed in 7 patients (25%). Six
patients (21.4%) had low attenuation lesions in the subcortical white
matter of the insula. A significant association was observed between
putaminal hemorrhage (OR=8, 95% CI=1.187-53.93, P=0.018) and subcortical
necrosis of the insula (OR=11, 95% CI=1.504-80.426, P=0.007) with death.
In addition to clinical and laboratory findings, presence of putaminal
hemorrhage and insular subcortex white matter necrosis are associated with
a poor clinical outcome in patients with methanol poisoning.[Taheri MS et
al; Eur J Radiol. 73 (2): 211-4 (2010)] **PEER REVIEWED** <a
/SURVEILLANCE/ ... Epidemiological and clinical data from one of the
largest methanol outbreaks in which all patients had detectable serum
methanol levels. Retrospective case series study of hospital and forensic
charts from the five hospitals where patients were treated. Of the 147
patients admitted with suspected methanol poisoning, the diagnosis was
confirmed in 111, of whom 25 (23 %) died. In addition, 43 patients died
outside the hospital, giving a total of 154 patients and a death toll of
68 (44 %). Outcome was related to the degree of metabolic acidosis, serum
methanol concentration, coma upon admission, and the patient's ability to
hyperventilate. Patients were treated with bicarbonate (85 %), ethanol (87
%), hemodialysis (71 %), and mechanical ventilation (61%) according to
clinical features and blood gases, since serum methanol concentrations
were analyzed retrospectively. Twenty patients (18 %) survived with
permanent sequelae, 18 suffered from impaired vision, and 3 developed
permanent brain damage.[Paasma R et al; Clin Toxicol (Phila). 45 (2):
152-7 (2007)] **PEER REVIEWED** <a
/SURVEILLANCE/ ... All cases of methanol exposures from January 2003 to
May 2005 were collected from the Texas Poison Center Network database
"Toxicall." Inclusion criteria were 1) methanol as primary exposure, and
2) documented route of exposure. Exclusion criteria were unknown, dermal,

and eye exposures. Data was extracted from documented calls to Texas
Poison Centers and analyzed using descriptive statistics. A total of 203
cases were collected from 6 regional Poison Centers. Eighty seven cases
had inhalation as the route of exposure, while 81 were methanol
ingestions. Carburetor cleaner was responsible for nearly all the
inhalational cases (79/87) while ingestions involved mostly windshield
washer fluid (39/81) and carburetor cleaner (20/81). Seventy-eight percent
of the inhalational exposures were intentional while most of the
ingestions were accidental (49/75) and suicidal (18/75). An anion gap was
documented in 31 of the inhalational cases and in 10 of the ingestions.
Dialysis, use of fomepizole, and vision loss were documented for both
types of exposure. Fifty-six percent of the inhalational group was
admitted compared to 46% of the ingestion group. ...[Givens M et al; West
J Emerg Med. 9 (3): 150-3 (2008)] **PEER REVIEWED** <a
target=new>PubMed Abstract Full text: <a
href='https://www.ncbi.nlm.nih.gov/pmc/?term=PMC2672266'
target=new>PMC2672266
/SURVEILLANCE/ ... A 2-year retrospective chart review of cases of
ingestion of model fuels containing methanol and nitromethane (MFNM) in
children, with both a methanol level and measured creatinine level. Seven
children, ages 19 months to 3 years, ingested MFNM. All seven children
were seen in a hospital and had measured methanol and creatinine levels.
All blood samples for methanol and creatinine were drawn within 3 hr of
ingestion with methanol estimation delayed up to 24 hr. Creatinine ranged
from 0.39 (0.034 mM/L) to 10.7 mg/dL (0.95 mM/L). All methanol levels were
< 10 mg/dL (0.31 mM/L) or reported as negative. Fomepizole was initiated
empirically in two patients due to delay in obtaining methanol analysis
results. Transient elevations of creatinine occurred in five of the seven
children. Blood urea nitrogen was within normal limits, and there was no
history of renal impairment in these children, suggesting the elevated
creatinine was mostly related to nitromethane ingestion. No child had a
significantly elevated methanol level.[Padmanabhan P et al; Clin Toxicol
(Phila). 49 (1): 45-7 (2011)] **PEER REVIEWED** <a
/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.

REVIEWED**
/BIOMONITORING/ ...A study /was conducted/ to determine if methanol in
breath is a useful indicator of blood levels following oral or dermal
exposure. ... 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:
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 uM/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)]
/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
SKIN, EYE AND RESPIRATORY IRRITATIONS:
/Methanol/ is an eye and skin irritant.[Lewis, R.J. Sr. (ed) Sax's
Dangerous Properties of Industrial Materials. 11th Edition.
Wiley-Interscience, Wiley & Sons, Inc. Hoboken, NJ. 2004., p. 2376]
**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
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
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
error 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
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).
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
PROBABLE ROUTES OF HUMAN EXPOSURE:
According to the 2006 TSCA Inventory Update Reporting data, the number of
persons reasonably likely to be exposed in the industrial manufacturing,
processing, and use of methanol is 1000 or greater; the data may be
greatly underestimated(1).[(1) US EPA; Inventory Update Reporting (IUR).
Non-confidential 2006 IUR Records by Chemical, including Manufacturing,
Processing and Use Information. Washington, DC: U.S. Environmental
Protection Agency. Available from, as of Sept 8, 2011:
http://cfpub.epa.gov/iursearch/index.cfm] **PEER REVIEWED**
NIOSH (NOES Survey 1981-1983) has statistically estimated that 1,620,617
workers (388,352 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; NOES. National
Occupational Exposure Survey conducted from 1981-1983. Estimated numbers
of employees potentially exposed to specific agents by 2-digit standard
industrial classification (SIC). Available from, as of Nov 2, 2011:
http://www.cdc.gov/niosh/ipcs/nicstart.html] **PEER REVIEWED**
Exposure to methanol can occur when people use certain paint strippers,
aerosol spray paints, wall paints, windshield wiper fluid, and small
engine fuel(1).[(1) US EPA; OPPT Chemical Fact Sheet (EPA 749-F-94-013),
Chemicals in the Environment: Methanol (CAS NO. 67-56-1). Available, as of
Sept 20, 2011: http://www.epa.gov/chemfact/f_methan.txt] **PEER REVIEWED**
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
concentrations 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**
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(2-4); in one study, it was detected in 3.6% of 387 expired air samples
collected from 54 volunteers at a geometric mean concentration 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**
REPORTED FATAL DOSE:
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:
EMERGENCY MEDICAL TREATMENT:
EMT COPYRIGHT DISCLAIMER:
The information contained in the Truven Health Analytics Inc. products is
intended as an educational aid only. All treatments or procedures are intended

to serve as an information resource for physicians or other competent healthcare
professionals performing the consultation or evaluation of patients and must be
interpreted in view of all attendant circumstances, indications and
contraindications.
The use of the Truven Health Analytics Inc. products is at
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products. All implied warranties of merchantability and fitness for a particular
purpose or use are hereby excluded. Truven Health Analytics Inc. does not assume
any responsibility or risk for your use of the Truven Health Analytics Inc.
products.<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, pancreatitis, and acute renal failure.
Rhabdomyolysis may occur in severe poisonings.
Hypomagnesemia, hypokalemia, and hypophosphatemia have
also been reported. 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
0.2.3.1 ACUTE EXPOSURE
A) WITH POISONING/EXPOSURE
1) Mild tachycardia is common with significant poisoning.
Tachypnea secondary to metabolic acidosis is common.
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
(International Agency for Research on Cancer, 2015;
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 Working Group on the Evaluation
of Carcinogenic Risks to Humans, 2007; IARC Working
Group on the Evaluation of Carcinogenic Risks to
Humans, 2006; 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
1) 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 fomepizole or ethanol 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) FOMEPIZOLE VS ETHANOL: 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) 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.
c) 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.
d) FOLATE: Folate increases the metabolism of formate.
Either folic acid or leucovorin (folinic acid) may be
used. In symptomatic patients (anion gap acidosis,
visual disturbances) and asymptomatic patients with
known or suspected methanol intoxication, administer
intravenous folic acid 1 to 2 mg/kg every 4 to 6 hours
for the first 24 hours, and continue until methanol is
cleared and acidosis resolved. Folate is removed by
hemodialysis so in patients undergoing hemodialysis,
administer one dose prior to and another at the
completion of hemodialysis.
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,
amount 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
H)
1)
I)
1)
J)
1)
K)
1)
0.4.3
A)
B)
0.4.4
A)
0.4.5
A)
1)
2)
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.
PITFALLS
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.
PHARMACOKINETICS
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.
TOXICOKINETICS
When alcohol dehydrogenase inhibitors are being used,
the apparent half-life is increased to approximately 50
hours.
DIFFERENTIAL DIAGNOSIS
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.
INHALATION EXPOSURE
Intentional inhalational exposures can result in
significant methanol levels and should be treated
similarly to oral ingestions.
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 an
inhaled beta2-adrenergic agonist. Consider systemic
corticosteroids in patients with significant
bronchospasm.
EYE EXPOSURE
DECONTAMINATION: Remove contact lenses and irrigate
exposed eyes with copious amounts of room temperature
0.9% saline or water for at least 15 minutes. If
irritation, pain, swelling, lacrimation, or photophobia
persist after 15 minutes of irrigation, the patient
should be seen in a healthcare facility.
DERMAL EXPOSURE
OVERVIEW
Rarely has repeated dermal exposure resulted in severe
methanol toxicity. It should be treated similarly to an
ingestion exposure.
DECONTAMINATION: Remove contaminated clothing and
jewelry and place them in plastic bags. Wash exposed
areas with soap and water for 10 to 15 minutes with
gentle sponging to avoid skin breakdown. A physician
may need to examine the area if irritation or pain

persists (Burgess et al, 1999).
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:
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)]
... Methanol-poisoned patients on fomepizole treatment may be separated
into two categories: 1) The critically ill patient, with severe metabolic
acidosis (base deficit > 15 mM) and/or visual disturbances should be
given buffer, fomepizole and immediate hemodialysis: dialysis removes the
toxic anion formate, and assists in correcting the metabolic acidosis,
thereby also reducing formate toxicity. The removal of methanol per se is
not important in this setting because fomepizole prevents further
production of formic acid. 2) The stable patient, with less metabolic
acidosis and no visual disturbances, should be given buffer and
fomepizole. This treatment allows for the possibility to delay, or even
drop, dialysis in this setting, because patients will not develop more
clinical features from methanol poisoning when fomepizole and bicarbonate
is given in adequate doses. Indications and triage for hemodialysis in
methanol poisonings should be modified. Delayed hemodialysis or even no
hemodialysis may be an option in selected cases.[Hovda KE, Jacobsen D; Hum
Exp Toxicol. 27 (7): 539-46 (2008)] **PEER REVIEWED** <a
/EXPERIMENTAL THER:/ ... Ranitidine /was tested/ as an antidote for
methanol acute toxicity and compared with ethanol and 4-methyl pyrazole
(4-MP). This study was conducted on 48 Sprague-Dawley rats, divided into 6
groups, with 8 rats in each group (one negative control group [C1], two
positive control groups [C2, C3] and three test groups [1, 2 and 3]). C2,
C3 and all test groups were exposed to nitrous oxide by inhalation, then,
C3 group was given methanol (3 g/kg orally). The three test groups 1, 2
and 3 were given ethanol (0.5 g/kg orally), 4-MP (15 mg/kg
intraperitoneally) and ranitidine (30 mg/kg intraperitoneally),
respectively, 4 hr after giving methanol. Rats were sacrificed and
heparinized, cardiac blood samples were collected for blood pH and
bicarbonate. Non-heparinized blood samples were collected for formate
levels by high performance liquid chromatography. Eye balls were
enucleated for histological examination of the retina. Ranitidine
corrected metabolic acidosis (p = .025), decreased formate levels (p =
.014) and improved the histological findings in the retina induced by
acute methanol toxicity.[El-Bakary AA et al; Hum Exp Toxicol. 29 (2):
93-101 (2010)] **PEER REVIEWED** <a
/EXPERIMENTAL THER:/ ... The effect of lycopene on methanol-induced liver
injury /was evaluated/ and ... the results /compared/ with those after
fomepizole, which is used in treatment of methanol intoxication.
Experiments were carried out with 30 female Wistar rats weighting 180-200
g. Rats were injected with an ip dose of 3 g/kg methanol as a 50% solution
in isotonic saline once for intoxication. Rats were pretreated with
fomepizole (50 mg/kg) and/or lycopene (10 mg/kg) before methanol. After 24
hr all the drug-treated and intoxicated rats were sacrificed under
anesthesia. Malondialdehyde (MDA) levels were determined in order to
assess lipid peroxidation, and caspase-3 activity was determined by
immunostaining of liver tissues to evaluate apoptosis. Methanol
administration significantly increased the MDA level and caspase-3
activity in liver. Pretreatment with lycopene and/or fomepizole decreased
the MDA levels significantly. Similarly, lycopene and fomepizole decreased
methanol-induced caspase-3 activity. The findings of the present study
demonstrate that methanol intoxication causes hepatic toxicity in rats and
that this is likely a result of reactive oxygen species and apoptosis
induction. Lycopene has protective effects against methanol-induced
hepatic injury similar to fomepizole. It was demonstrated for the first
time that both lycopene and fomepizole prevent methanol-induced hepatic
injury by reducing the increase of lipid oxidation and caspase-3
activation.[Kurcer MA et al; Med Food. 13 (4): 985-91 (2010)] **PEER
REVIEWED** <a
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
methanol... 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)]
Emergency and supportive measures. Maintain an open airway and assist
ventilation if necessary. Treat coma and seizures if they occur. Treat
metabolic acidosis with iv sodium bicarbonate. Correction of acidosis
should be guided by arterial blood gases.[OLSON, K.R. (Ed). Poisoning and
Drug Overdose, Sixth Edition. McGraw-Hill, New York, NY 2012, p. 279]
**PEER REVIEWED**
Specific drugs and antidotes. 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. Folic or folinic
acid may enhance the conversion of formate to carbon dioxide and
water.[OLSON, K.R. (Ed). Poisoning and Drug Overdose, Sixth Edition.
McGraw-Hill, New York, NY 2012, p. 279] **PEER REVIEWED**
Decontamination.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 and Drug Overdose, Sixth
Edition. McGraw-Hill, New York, NY 2012, p. 279] **PEER REVIEWED**
Enhanced elimination. Hemodialysis rapidly removes both methanol
(half-life reduced to 3-6 hr) and formate. The indication for dialysis
include: suspected methanol poisoning with significant metabolic acidosis;
visual abnormalities; renal failure; or an osmolar gap > 10 mOsm/L, or a
measured serum methanol concentration > 50 mg/dL. Dialysis fomepizole,
or ethanol should be continued until the methanol concentration is less

than 20 mg/dL and the osmolar and anion gaps are normalized.[OLSON, K.R.
(Ed). Poisoning and Drug Overdose, Sixth Edition. McGraw-Hill, New York,
NY 2012, p. 279] **PEER REVIEWED**
Immediate first aid: Ensure that adequate decontamination has been carried
out. If patient is not breathing, start artificial respiration, preferably
with a demand-valve resuscitator, bag-valve-mask device, or pocket mask,
as trained. Perform CPR as necessary. Immediately flush contaminated eyes
with gently flowing water. Do not induce vomiting. If vomiting occurs,
lean patient forward or place on left side (head-down position, if
possible) to maintain an open airway and prevent aspiration. Keep patient
quiet and maintain normal body temperature. Obtain medical attention.
/Methyl Alcohol and Related Compounds/[Currance, P.L. Clements, B.,
Bronstein, A.C. (Eds).; Emergency Care For Hazardous Materials Exposure.
3Rd edition, Elsevier Mosby, St. Louis, MO 2005, p. 235] **PEER REVIEWED**
Basic treatment: Establish a patent airway (oropharyngeal or
nasopharyngeal airway, if needed). 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
0.9% saline (NS) 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/[Currance, P.L. Clements, B., Bronstein, A.C. (Eds).; Emergency
Care For Hazardous Materials Exposure. 3Rd edition, Elsevier Mosby, St.
Louis, MO 2005, p. 235-6] **PEER REVIEWED**
Advanced treatment: Consider orotracheal or nasotracheal intubation for
airway control in the patient who is unconscious, has severe pulmonary
edema, or is in severe respiratory distress. Start IV administration of
0.9% saline (NS) or lactated Ringer's (LR) /SRP: "To keep open", minimal
flow rate/. For hypotension with signs of hypovolemia, administer fluid
cautiously. Watch for signs of fluid overload ... . Treat seizures with
diazepam or lorazepam ... . Use proparacaine hydrochloride to assist eye
irrigation ... . /Methyl Alcohol and Related Compounds/[Currance, P.L.
Clements, B., Bronstein, A.C. (Eds).; Emergency Care For Hazardous
Materials Exposure. 3Rd edition, Elsevier Mosby, St. Louis, MO 2005, p.
236] **PEER REVIEWED**
...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 mM/L (11.8-42.2), arterial pH 7.34 (7.11-7.51), and bicarbonate
17.5 mM/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
ANIMAL TOXICITY STUDIES:
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
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,
folate-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;
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

/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:
/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
/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/ Methyl alcohol (methanol, wood
alcohol) is a drastic poison ... Its consumption leads to atrophy of the
optic nerve, causing permanent blindness, and to depression of cardiac and
voluntary muscle, resulting in death.[Humphreys, D.J. Veterinary
Toxicology. 3rd ed. London, England: Bailliere Tindell, 1988., p. 184]
**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.;
/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
administration, 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)]
/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.[Wecker JR, Ison JR; Toxicol Appl Pharm 74
(2): 258-66 (1984)] **PEER REVIEWED**
/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:

/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).
/LABORATORY ANIMALS: Subchronic or Prechronic Exposure/ Male Wistar albino
rats were intoxicated with methanol (2.37 g/kg bw ip) for detecting
toxicity levels for one day, 15 days and 30 days, respectively.
Administration of methanol at 15 and 30 days significantly (p < 0.05)
increased lipid peroxidation and decreased the enzymatic (superoxide
dismutase, catalase, glutathione peroxidase) and non-enzymatic
antioxidants (reduced glutathione and vitamin C) in lymphoid organs.
However, lipid peroxidation and enzymatic and non-enzymatic antioxidants
in the acute methanol exposed group animals were found to be significantly
(p < 0.05) increased. In one day methanol intoxication, the levels of
free radicals initially increased, and to remove these free radicals,
antioxidants levels were elevated, which generally prevented oxidative
cell damage. But in longer periods of intoxication, when the generation of
reactive free radicals overwhelmed the antioxidant defense, lipid
peroxidation increased. Further, decreased antioxidants in 15 and 30 days
methanol intoxication may have been due to overutilization of
non-enzymatic and enzymatic antioxidants to scavenge the products of lipid
peroxidation. In addition, the liver and kidney markers of serum aspartate
aminotransferase (AST), alanine aminotransferase (ALT), urea and
creatinine significantly increased. This study concludes that exposure to
methanol causes oxidative stress by altering the oxidant/antioxidant
balance in lymphoid organs of the rat.[Parthasarathy NJ et al; J Occup
Health. 48 (1): 20-7 (2006)] **PEER REVIEWED** <a
/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
/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
/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
/LABORATORY ANIMALS: Chronic Exposure or Carcinogenicity/ ... Oncogenicity
studies of methanol were conducted by inhalation for approximately 20
hrs/day at up to 1000 ppm in F344 rats and B6C3F1 mice (NEDO), and by
incorporation into drinking water at up to 20,000 ppm in Sprague-Dawley
rats. No increased neoplasms were found in the NEDO rat and mouse
inhalation studies, even at air levels (up to 1000 ppm for > 19
hours/day, 7 days/week) that caused 10-fold increased blood methanol
levels. The maximum dose level was 600 mg/kg/day. The breakdown of
methanol to formaldehyde in rats is saturated at doses above 600 mg/kg.
... Thus, higher inhalation exposure concentrations are not expected to
lead to tumors in rats or mice. ... The data from genotoxicity studies,
the inhalation and drinking water oncogenicity studies of methanol in rats
and mice, and mode of action considerations support a conclusion that
methanol is not likely to be carcinogenic in humans.[Cruzan G; Crit Rev
Toxicol. 39 (4): 347-63 (2009)] **PEER REVIEWED** <a
/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
/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
/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
/LABORATORY ANIMALS: Developmental or Reproductive Toxicity/ 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 hr 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
hr 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
/LABORATORY ANIMALS: Developmental or Reproductive Toxicity/ ...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
/LABORATORY ANIMALS: Developmental or Reproductive Toxicity/ ... Rat and
mouse whole embryo cultures are used to distinguish toxicity of Methanol
(CH3OH) and its metabolites, formaldehyde (HCHO) and formate (HCOONa),
which are produced following transit through the visceral yolk sac (VYS),
via addition to culture medium, or by direct embryonic exposure through
microinjection into the amnion. Embryonic viability, increased
dysmorphogenesis, and decreased growth parameters were altered in a
dose-dependent fashion for each compound. Mouse embryos were more
sensitive than rat, as indicated by significant decreases in viability at
comparable, lower concentrations. HCHO produced dysmorphogenesis and
caused embryolethality at nearly 1000-fold lower concentrations (0.004
mg/mL) than seen with either CH3OH or HCOONa. All agents produced
incomplete axial rotation and delayed neural tube closure in mice, but
only CH3OH elicited similar effects in the rat. Increased growth
retardation, blood pooling in the head and VYS, enlarged pericardium,
accumulation of necrotic matter in the amnion, and hypoplastic
prosencephalon were observed in both species with all compounds.
Microinjection of compounds into the amnion produced higher mortality in
mouse and rat, compared to equimolar amounts added to the culture medium.
CH3OH did not prevent neural tube closure in the rat when microinjected.
HCHO is the most embryotoxic CH3OH metabolite and elicits the entire
spectrum of lesions produced by CH3OH. The VYS serves a general protective
role against toxicity and inherent differences in the embryonic metabolism
of CH3OH may determine species sensitivity.[Hansen JM et al; Birth Defects
Res A Clin Mol Teratol. 73 (2): 72-82 (2005)] **PEER REVIEWED** <a
/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).
/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
/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
**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
/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
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:

/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).
/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://esis.jrc.ec.europa.eu/] **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
birth, 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

/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
/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
/LABORATORY ANIMALS: Developmental or Reproductive Toxicity/ 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.
Compared 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
/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
those 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
/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 rats 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.;
/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
/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
/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
/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
/LABORATORY ANIMALS: Developmental or Reproductive Toxicity/ ...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
/LABORATORY ANIMALS: Developmental or Reproductive Toxicity/ 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 (14)C-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.[Huang YS et al; Repro Toxicol 15 (4): 429-35
/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).
/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
REVIEWED**
/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/ 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)] **PEER REVIEWED**
/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
/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.;
/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
/GENOTOXICITY/ Urine from mice administered five daily doses of methanol
(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
/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)]
**PEER REVIEWED**
/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 and 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
/ALTERNATIVE and 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://esis.jrc.ec.europa.eu/] **PEER REVIEWED**
/IMMUNOTOXICITY/ /Researchers/ compared effects of gasoline and methanol
engine exhausts on immune function in RAW264.7 cell and rabbit alveolar
macrophages. Results showed that both gasoline and methanol engine exhaust
could evidently inhibit RAW264.7 cell proliferation, promote RAW264.7 cell
apoptosis, decrease E-rosette formation rate and inhibit anti-tumor
effects of alveolar macrophages, at the same time, these effects of
gasoline engine exhaust were far stronger than those of methanol engine
exhaust. In addition, gasoline engine exhaust could significantly inhibit
activities of ADCC of alveolar macrophages, but methanol engine exhaust
could not.[Che W et al; Toxicol In Vitro. 24 (4): 1119-25 (2010)] **PEER
REVIEWED** <a
/OTHER TOXICITY INFORMATION/ ...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
/OTHER TOXICITY INFORMATION/ To assess the toxicity of the /one -carbon
(C1)/ compound methanol ... gene expression profiles of treated baker's
yeast were analyzed using DNA microarrays. Among approximately 6,000 open
reading frames (ORFs), 314 were repressed and 375 were induced in response
to methanol. The gene process category "energy" comprised the greatest
number of induced genes while "protein synthesis" comprised the greatest
number of repressed genes. Products of genes induced by methanol were
mainly integral membrane proteins or were localized to the plasma
membrane.[Yasokawa D et al; Appl Biochem Biotechnol. 160 (6): 1685-98
/OTHER TOXICITY INFORMATION/ 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 in 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).
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://esis.jrc.ec.europa.eu/] **PEER
REVIEWED**
/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
/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/L). 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
/AQUATIC SPECIES/ 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
/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
ethanol, 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
/OTHER TERRESTRIAL SPECIES/ ... /Researchers/ reported the tolerance to
and the metabolism of methanol by Ostrinia furnacalis /(Asian corn borer
moth)/ third-instar larvae. When larvae were exposed to dietary methanol,
formaldehyde and formic acid for 72 hr, the estimated LC(50) value was 28,
40 and 29 mg/g diet, respectively. Toxicity of methanol was enhanced by
4-methylpyrazole, 3-amino-1,2,4-triazole and piperonyl butoxide, and
toxicity of formaldehyde was increased by 3-amino-1,2,4-triazole and
piperonyl butoxide. However, triphenyl phosphate had little synergistic
effects on both methanol and formaldehyde. These data indicate that
alcohol dehydrogenase, and probably catalase and cytochrome P450
monooxygenase oxidize methanol to formaldehyde, catalase and cytochrome
P450 monooxygenase catalyze formaldehyde to formic acid, water and carbon
dioxide, and carboxylesterase may have a minor effect. Several fatty acid
methyl esters (FAMEs) were identified from extracts of the frass of larvae
which had been exposed to a methanol-contained diet, in contrast to those
on a methanol-free artificial diet. In vitro tests revealed that a crude
enzyme solution from the larvae could synthesize FAMEs from corresponding
fatty acids and methanol. In addition, dietary methanol induced higher
esterase activities in the first-, second- and third-instar larvae. These
findings demonstrate that both oxidative metabolism and non-oxidative
metabolism are partially responsible for methanol elimination in O.
furnacalis larvae.[Guo L et al; J Insect Physiol. 56 (3): 260-5 (2010)]
NON-HUMAN TOXICITY VALUES:
LD50 Rat oral 5628 mg/kg[Lewis, R.J. Sr. (ed) Sax's Dangerous Properties
of Industrial Materials. 11th Edition. Wiley-Interscience, Wiley &
Sons, Inc. Hoboken, NJ. 2004., p. 2376] **PEER REVIEWED**
LD50 Rabbit oral 14.4 g/kg[Bingham, E.; Cohrssen, B.; Powell, C.H.;
LD50 Monkey oral 2-3 g/kg[Bingham, E.; Cohrssen, B.; Powell, C.H.; Patty's
LD50 Mouse oral 7300 mg/kg[Lewis, R.J. Sr. (ed) Sax's Dangerous Properties
LD50 Dog oral 8000 mg/kg bw[European Chemicals Bureau; IUCLID Dataset,
LD50 Rabbit dermal 15,840 mg/kg[National Research Council; Prudent
Practices in the Laboratory. Handling and Management of Chemical Hazards.
the National Academies Press, Washington, D.C. 2011, p. CD] **PEER
REVIEWED**
LD50 Rabbit dermal 15,800 mg/kg bw[European Chemicals Bureau; IUCLID
LC50 Rat inhalation > 145,000 ppm/1 hr[National Research Council;
Prudent Practices in the Laboratory. Handling and Management of Chemical
Hazards. the National Academies Press, Washington, D.C. 2011, p. CD]
**PEER REVIEWED**
LC50 Rat inhalation 64000 ppm/4 hr[Lewis, R.J. Sr. (ed) Sax's Dangerous
Properties of Industrial Materials. 11th Edition. Wiley-Interscience,
Wiley & Sons, Inc. Hoboken, NJ. 2004., p. 2376] **PEER REVIEWED**
LC50 Rat inhalation 87.5 mg/L/6 hr[European Chemicals Bureau; IUCLID
LC50 Cat inhalation 43.68 mg/L/6 hr[European Chemicals Bureau; IUCLID
LC50 Cat inhalation 85.41 mg/L/4.5 hr[European Chemicals Bureau; IUCLID
LD50 Rat ip 7529 mg/kg[Lewis, R.J. Sr. (ed) Sax's Dangerous Properties of
Industrial Materials. 11th Edition. Wiley-Interscience, Wiley & Sons,
Inc. Hoboken, NJ. 2004., p. 2376] **PEER REVIEWED**
LD50 Guinea pig ip 3556 mg/kg bw[European Chemicals Bureau; IUCLID
LD50 Rabbit ip 1826 mg/kg bw[European Chemicals Bureau; IUCLID Dataset,
LD50 Mouse ip 10765 mg/kg[Lewis, R.J. Sr. (ed) Sax's Dangerous Properties
LD50 Hamster ip 8555 mg/kg bw[European Chemicals Bureau; IUCLID Dataset,

LD50 Macaca nemestrina (Pigtail monkey) ip 3-4 g/kg[WHO; Environ Health
LD50 Mouse sc 9800 mg/kg[Lewis, R.J. Sr. (ed) Sax's Dangerous Properties
LD50 Mouse sc 4100 mg/kg bw[European Chemicals Bureau; IUCLID Dataset,
LD50 Rat iv 2131 mg/kg[Lewis, R.J. Sr. (ed) Sax's Dangerous Properties of
Industrial Materials. 11th Edition. Wiley-Interscience, Wiley & Sons,
Inc. Hoboken, NJ. 2004., p. 2376] **PEER REVIEWED**
LD50 Mouse iv 4710 mg/kg[Lewis, R.J. Sr. (ed) Sax's Dangerous Properties
LD50 Rabbit iv 8907 mg/kg bw[European Chemicals Bureau; IUCLID Dataset,
ECOTOXICITY VALUES:
EC50; Species: Chlorella fusca ssp. vacuolata (Green Algae) strain 21115;
Conditions: freshwater, static, 28 deg C, pH 6.9; Concentration: 0.77
umol/L for 24 hr; Effect: decreased population growth rate /100%
purity/[Adema DMM; Aquatic Toxicity of Compounds that may be Carried by
Ships (Marpol 1973 Annex II). A Progress Report for 1985, Tech Rep No
R85/217: 40 (1985) as cited in the ECOTOX database. Available from, as of
November 15, 2011: http://cfpub.epa.gov/ecotox/quick_query.htm] **PEER
REVIEWED**
EC50; Species: Pseudokirchneriella subcapitata (Green Algae) 15000
cells/mL; Conditions: freshwater, static, 24 deg C; Concentration: 3010
ug/L for 48 hr (95% confidence interval: 1910-5570 ug/L); Effect:
physiology photosynthesis /99% purity formulation/[Hsieh SH et al; Water
Res 40 (10): 1957-64 (2006) as cited in the ECOTOX database. Available
from, as of November 15, 2011:
http://cfpub.epa.gov/ecotox/quick_query.htm] **PEER REVIEWED**
EC50; Species: Pseudokirchneriella subcapitata (Green Algae) 15000
cells/mL; Conditions: freshwater, static, 24 deg C; Concentration:
> 60400 ug/L for 48 hr; Effect: population growth rate /99% purity
formulation/[Hsieh SH et al; Water Res 40 (10): 1957-64 (2006) as cited in
the ECOTOX database. Available from, as of November 15, 2011:
LC50; Species: Pimephales promelas (fathead minnows) 28-29 days old;
Conditions: flow through ; Test conditions: Water temp= 25 deg C,
dissolved oxygen= 7.3 mg/L, water hardness= 43.5 mg/L calcium carbonate,
alkalinity= 46.6 calcium carbonate, tank volume= 6.3 L, additions= 5.71
V/D, pH= 7.66 (0.03). Concentration 29.4 g/L for 96 hr[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,
LC50; Species: Pimephales promelas (Fathead minnow) 28-32 day old, weight
0.126 g; Conditions: flow through, 23.3+/-1.7 deg C, hardness 46.4 mg/L
CaCO3, pH 7.0-8.0; Concentration: 29,700 mg/L for 24 hr /from table/[WHO;
REVIEWED**
LC50; Species: Pimephales promelas (Fathead minnow) 30 day old, weight
0.12 g; Conditions: flow through, 24-26 deg C, hardness 45.5 mg/L CaCO3,
pH 7.5; Concentration: 28,100 mg/L for 96 hr /from table/[WHO; Environ
REVIEWED**
LC50; Species: Artemia salina (Brine shrimp) age 24 hr; Conditions:
seawater, static, 25 deg C; Concentration: 1578.84 mg/L for 24 hr /from
table/[WHO; Environ Health Criteria 196: Methanol p.117 (1997). Available
LC50; Species: Oncorhynchus mykiss (Rainbow trout) weight 0.8 g;
Conditions: static, 12 deg C, hardness 44 mg/L CaCO3, pH 7.4;
Concentration: 19,000 mg/L for 96 hr /from table/[WHO; Environ Health
LC50; Species: Oncorhynchus mykiss (Rainbow trout) juvenile, weight 0.813
g; Conditions: flow through, 12.7+/-1 deg C, hardness 46.4 mg/L CaCO3, pH
7.0-8.0; Concentration: 20,300 mg/L for 24 hr /from table/[WHO; Environ
REVIEWED**
LC50; Species: Oncorhynchus mykiss (Rainbow trout) juvenile, weight 0.813
g; Conditions: flow-through, 12.7+/-1 deg C, hardness 46.4 mg/L CaCO3, pH
7.0-8.0; Concentration: 20,100 mg/L for 96 hr /from table/[WHO; Environ
REVIEWED**
LC50; Species: Lepomis macrochirus (Bluegill); Conditions: flow through;
Concentration: 15,400 mg/L for 96 hr[European Chemicals Bureau; IUCLID
LC50; Species: Lepomis macrochirus (Bluegill); Conditions: flow through;

Concentration: 19,230 mg/L for 24 hr[European Chemicals Bureau; IUCLID
LC50; Species: Lepomis macrochirus (Bluegill sunfish) juvenile, weight
3.07 g; Conditions: flow-through, 19.8+/-2.3 deg C, hardness 46.4 mg/L
REVIEWED**
LC50; Species: Lepomis macrochirus (Bluegill sunfish) juvenile, weight
3.07 g; Conditions: flow-through, 19.8+/-2.3 deg C, hardness 46.4 mg/L
REVIEWED**
LC50; Species: Nitocra spinipes (Harpacticoid copepod) adult; Conditions:
static, 21+/-1 deg C, pH 7.9; Concentration: 12,000 mg/L for 96 hr /from
LC50; Species: Poecilia reticulata (Guppy); Conditions: semistatic;
Concentration: 11.5 mg/L for 14 days[European Chemicals Bureau; IUCLID
LC50; Species: Poecilia reticulata (Guppy) age 2-3 months; Conditions:
semistatic (test solutions renewed every 24 hours), 21-23 deg C, hardness
25 mg/L CaCO3; Concentration: 10,860 mg/L for 7 days /from table/[WHO;
REVIEWED**
LC50; Species: Alburnus alburnus (Bleak) length 8 cm; Conditions: static,
10 deg C, pH 7.9; Concentration: 28,000 mg/L for 96 hr /from table/[WHO;
REVIEWED**
LC50; Species: Leuciscus idus melanotus (Golden orfe); Condtions: static;
Concentration: > 10,000 mg/L for 48 hr[European Chemicals Bureau; IUCLID
EC50; Species: Daphnia magna (Water flea); Conditions: static, 20 deg C,
total hardness 2.5 mmol/L CaCO3, pH 7.8-8.2; Concentration: > 10,000
mg/L for 24 hr; Effect: immobilization /from table/[WHO; Environ Health
LC50; Species: Gammarus fasciatus (Scud); Concentration: > 100 mg/L for
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://esis.jrc.ec.europa.eu/] **PEER REVIEWED**
LC50; Species: Helisoma trivolvis (aquatic mollusk); Concentration:

> 100 mg/L for 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:
LC50; Species: Dugesia tigrina (aquatic worm); Concentration: > 100 mg/L
for 96 hr /Conditions of bioassay not specified in source
LC50; Species: Ceriodaphnia dubia (Water flea); Concentration: 11 mg/L for
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:
LC50; Species: Lumbriculus variegatus (aquatic worm); Concentration:
> 100 mg/L for 96 hr /Conditions of bioassay not specified in source
EC50; Species: Photobacterium posphoreum (marine bacterium);
Concentration: 14,700 mg/L for 15 min; Effect: inhibition of luminescence
/Conditions of bioassay not specified in source examined/[WHO; Environ
REVIEWED**
LC50; Species: Photobacterium posphoreum (marine bacterium);
Concentration: 7690 mg/L for 4 hr /Conditions of bioassay not specified in
source examined/[WHO; Environ Health Criteria 196: Methanol p.114 (1997).
LC50; Species: Paramecium caudatum (Ciliate protozoan); Concentration:
44,860 mg/L for 10 min /Conditions of bioassay not specified in source
examined/[WHO; Environ Health Criteria 196: Methanol p.114 (1997).
LC50; Species: Daphnia pulex (Water flea) age < 24 hr; Conditions:
static, 22 deg C, hardness 23+/-2 mg/L CaCO3; Concentration: 19,500 mg/L
for 18 hr /from table/[WHO; Environ Health Criteria 196: Methanol p.116
EC50; Species: Daphnia obtusa (Water flea) age < 24 hr; Conditions:
static, 20+/-2 deg C, hardness 250 mg/L CaCO3, pH 7.8+/-0.2;
Concentration: 23,500 mg/L for 24 hr; Effect: immobilization /from
EC50; Species: Daphnia obtusa (Water flea) age < 24 hr; Conditions:
static, 20+/-2 deg C, hardness 250 mg/L CaCO3, pH 7.8+/-0.2;
Concentration: 22,200 mg/L for 48 hr; Effect: immobilization /from

LC50; Species:
static, 15 deg
Environ Health
July 19, 2005:
REVIEWED**
Crangon crangon (Brown shrimp) adult; Conditions: seawater,

C; Concentration: 1975 mg/L for 48 hr /from table/[WHO;
Criteria 196: Methanol p.117 (1997). Available from, as of
http://www.inchem.org/documents/ehc/ehc/ehc196.htm] **PEER
LC50; Species: Crangon crangon (Brown shrimp) adult; Conditions:

semistatic (test solutions renewed every 24 hr), 15 deg C, seawater;
Concentration: 1340 mg/L for 96 hr /from table/[WHO; Environ Health
LC50; Species: Crangon crangon (Brown shrimp) adult; Conditions: seawater,
static 24.5 deg C; Concentration: 10,000 mg/L for 24 hr /from table/[WHO;
REVIEWED**
LC50; Species: Mytilus edulis (Mussel) length 5-7 cm; Conditions:
flow-through, 15+/-0.5 deg C, seawater; Concentration: 15,900 mg/L for 96
hr /from table/[WHO; Environ Health Criteria 196: Methanol p.118 (1997).
LC50; Species: Palaemonetes kadiakensis (Glass shrimp) juvenile;
Conditions: static, 23+/-2 deg C; Concentration: 21,900 mg/L for 18 hr
/from table/[WHO; Environ Health Criteria 196: Methanol p.117 (1997).
LC50; Species: Cardium edule (Cockle) adult; Conditions: seawater, static,
15 deg C; Concentration: 7900 mg/L for 48 hr /from table/[WHO; Environ
REVIEWED**
LC50; Species: Hyallela azteca (Scud) juvenile; Conditions: static, 23+/-2
deg C; Concentration: 19,350 mg/L for 18 hr /from table/[WHO; Environ
REVIEWED**
LC50; Species: Agonus cataphractus (Armed bullhead) adult; Conditions:
semistatic (test solutions renewed every 24 hours), 15 deg C, seawater;
Concentration: 7900-26,070 mg/L for 96 hr /from table/[WHO; Environ Health
EC50; Species: Tetrahymena pyriformis (Protozoa); Concentration: 18756.34
mg/L for 48 hr; Effect: population growth inhibition test /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://esis.jrc.ec.europa.eu/] **PEER
REVIEWED**
LC50; Species: Anodonta imbecilis (Mussel); Condtiions: static;
Concentration: 37.02 mg/L for 48 hr[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; Species: Oryzias latipes (Medaka); Conditions: static;
Concentration: > 10,000 mg/L for 24 hr /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:
EC50; Species: Oryzias latipes (Medaka) age 0.5 hr post-fertilization
eggs, orange/red strain; Conditions: freshwater, static, 25 deg C;
Concentration: 1.16% v/v for 200 hr; Effect: development, decreased normal
/ > 99% purity/[Gonzalez-Doncel M et al; Ecotoxicol Environ Saf 69 (1):
95-103 (2008) as cited in the ECOTOX database. Available from, as of
November 15, 2011: http://cfpub.epa.gov/ecotox/quick_query.htm] **PEER
REVIEWED**
EC50; Species: Oryzias latipes (Medaka) age 0.5 hr post-fertilization
eggs, orange/red strain; Conditions: freshwater, static, 25 deg C;
Concentration: 1.84% v/v for 200 hr (95% confidence interval: 1.62-2.10%
v/v); Effect: decreased hatching / > 99% purity/[Gonzalez-Doncel M et al;
Ecotoxicol Environ Saf 69 (1): 95-103 (2008) as cited in the ECOTOX
database. Available from, as of November 15, 2011:
METABOLISM/ PHARMACOKINETICS:
METABOLISM/ METABOLITES:
Metabolism of methanol occurs in a three-step process initially involving
oxidation to formaldehyde by hepatic alcohol dehydrogenase, which is a
saturable rate-limiting process. In the second step, formaldehyde is
oxidized by aldehyde dehydrogenase to formic acid or formate depending on
the pH. In the third step, formic acid is detoxified by a folate-dependent
pathway to carbon dioxide. Elimination of methanol from the blood appears
to be slow in all species, especially when compared to ethanol. In humans,
urinary methanol concentrations have been found to be proportional to the
concentration of methanol in blood.[WHO/Health and Safety Guide No. 105
for Methanol (67-56-1) (1997). Available from, as of September 29, 2011:
http://www.inchem.org/pages/hsg.html] **PEER REVIEWED**
Methanol is primarily metabolized by oxidation to formaldehyde and then to
formate. ...[Parthasarathy NJ et al; J Occup Health. 48 (1): 20-7 (2006)]
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.;
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
to monkeys, 78% of the activity was recovered within 24 hr as exhaled
CO2.[Bingham, E.; Cohrssen, B.; Powell, C.H.; Patty's Toxicology Volumes
**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.
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**
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
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
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
approximately/... 8.4 mg/sq cm/hr. Time to peak serum concentration...
after ingestion /is/... 30-60 minutes for methanol... .[Goldfrank, L.R.
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
... 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
air.[Clayton, G. D. and F.
and Toxicology: Volume 2A,
Wiley Sons, 1981-1982., p.
by animals was eliminated in expired

E. Clayton (eds.). Patty's Industrial Hygiene
2B, 2C: Toxicology. 3rd ed. New York: John
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
Rabbits given a single oral dose of methanol (2
to 1.1% of it as formate and 13 to 20% of it as
within 47 to 143 hr.[Bingham, E.; Cohrssen, B.;
Toxicology Volumes 1-9 5th ed. John Wiley &
to 10 g/kg) excreted 0.1

methanol in the urine
Powell, C.H.; Patty's
Sons. New York, N.Y.
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,
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.;
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,
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.;
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,
respectively, 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
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 &
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
**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
**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
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.;
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
... 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.;
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
...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
REVIEWED**
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).
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
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
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:
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
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:
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:
twice 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
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**
BIOLOGICAL HALF-LIFE:
... The mean plasma half-life of methanol during fomepizole treatment was
52 hr (range 22-87); the higher the serum methanol, the longer the
half-life. ...[Hovda KE et al; Clin Toxicol (Phila). 43 (4): 221-7 (2005)]
Biological half-life of methanol elimination in expired air is 1.5 hr
after either oral or dermal application.[Dutkiewicz B; Int Congr SerExcerpta 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
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
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
... 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
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.;
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
metabolic 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
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).
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).
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
cytochrome 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
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
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.;
INTERACTIONS:
REVIEWED**
... Ranitidine /was tested/ as an antidote for methanol acute toxicity and
compared with ethanol and 4-methyl pyrazole (4-MP). This study was
conducted on 48 Sprague-Dawley rats, divided into 6 groups, with 8 rats in
each group (one negative control group [C1], two positive control groups
[C2, C3] and three test groups [1, 2 and 3]). C2, C3 and all test groups
were exposed to nitrous oxide by inhalation, then, C3 group was given
methanol (3 g/kg orally). The three test groups 1, 2 and 3 were given
ethanol (0.5 g/kg orally), 4-MP (15 mg/kg intraperitoneally) and
ranitidine (30 mg/kg intraperitoneally), respectively, 4 hr after giving
methanol. Rats were sacrificed and heparinized, cardiac blood samples were
collected for blood pH and bicarbonate. Non-heparinized blood samples were
collected for formate levels by high performance liquid chromatography.
Eye balls were enucleated for histological examination of the retina.
Ranitidine corrected metabolic acidosis (p = .025), decreased formate
levels (p = .014) and improved the histological findings in the retina
induced by acute methanol toxicity.[El-Bakary AA et al; Hum Exp Toxicol.
29 (2): 93-101 (2010)] **PEER REVIEWED** <a
... The effect of lycopene on methanol-induced liver injury /was
evaluated/ and ... the results /compared/ with those after fomepizole,
which is used in treatment of methanol intoxication. Experiments were
carried out with 30 female Wistar rats weighting 180-200 g. Rats were
injected with an ip dose of 3 g/kg methanol as a 50% solution in isotonic
saline once for intoxication. Rats were pretreated with fomepizole (50
mg/kg) and/or lycopene (10 mg/kg) before methanol. After 24 hr all the
drug-treated and intoxicated rats were sacrificed under anesthesia.
Malondialdehyde (MDA) levels were determined in order to assess lipid
peroxidation, and caspase-3 activity was determined by immunostaining of
liver tissues to evaluate apoptosis. Methanol administration significantly
increased the MDA level and caspase-3 activity in liver. Pretreatment with
lycopene and/or fomepizole decreased the MDA levels significantly.
Similarly, lycopene and fomepizole decreased methanol-induced caspase-3
activity. The findings of the present study demonstrate that methanol
intoxication causes hepatic toxicity in rats and that this is likely a
result of reactive oxygen species and apoptosis induction. Lycopene has
protective effects against methanol-induced hepatic injury similar to
fomepizole. It was demonstrated for the first time that both lycopene and
fomepizole prevent methanol-induced hepatic injury by reducing the
increase of lipid oxidation and caspase-3 activation.[Kurcer MA et al; Med
Food. 13 (4): 985-91 (2010)] **PEER REVIEWED** <a
...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.
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.
... 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
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
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
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
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**
PHARMACOLOGY:
INTERACTIONS:

REVIEWED**
... Ranitidine /was tested/ as an antidote for methanol acute toxicity and
compared with ethanol and 4-methyl pyrazole (4-MP). This study was
conducted on 48 Sprague-Dawley rats, divided into 6 groups, with 8 rats in
each group (one negative control group [C1], two positive control groups
[C2, C3] and three test groups [1, 2 and 3]). C2, C3 and all test groups
were exposed to nitrous oxide by inhalation, then, C3 group was given
methanol (3 g/kg orally). The three test groups 1, 2 and 3 were given
ethanol (0.5 g/kg orally), 4-MP (15 mg/kg intraperitoneally) and
ranitidine (30 mg/kg intraperitoneally), respectively, 4 hr after giving
methanol. Rats were sacrificed and heparinized, cardiac blood samples were
collected for blood pH and bicarbonate. Non-heparinized blood samples were
collected for formate levels by high performance liquid chromatography.
Eye balls were enucleated for histological examination of the retina.
Ranitidine corrected metabolic acidosis (p = .025), decreased formate
levels (p = .014) and improved the histological findings in the retina
induced by acute methanol toxicity.[El-Bakary AA et al; Hum Exp Toxicol.
29 (2): 93-101 (2010)] **PEER REVIEWED** <a
... The effect of lycopene on methanol-induced liver injury /was
evaluated/ and ... the results /compared/ with those after fomepizole,
which is used in treatment of methanol intoxication. Experiments were
carried out with 30 female Wistar rats weighting 180-200 g. Rats were
injected with an ip dose of 3 g/kg methanol as a 50% solution in isotonic
saline once for intoxication. Rats were pretreated with fomepizole (50
mg/kg) and/or lycopene (10 mg/kg) before methanol. After 24 hr all the
drug-treated and intoxicated rats were sacrificed under anesthesia.
Malondialdehyde (MDA) levels were determined in order to assess lipid
peroxidation, and caspase-3 activity was determined by immunostaining of
liver tissues to evaluate apoptosis. Methanol administration significantly
increased the MDA level and caspase-3 activity in liver. Pretreatment with
lycopene and/or fomepizole decreased the MDA levels significantly.
Similarly, lycopene and fomepizole decreased methanol-induced caspase-3
activity. The findings of the present study demonstrate that methanol
intoxication causes hepatic toxicity in rats and that this is likely a
result of reactive oxygen species and apoptosis induction. Lycopene has
protective effects against methanol-induced hepatic injury similar to
fomepizole. It was demonstrated for the first time that both lycopene and
fomepizole prevent methanol-induced hepatic injury by reducing the
increase of lipid oxidation and caspase-3 activation.[Kurcer MA et al; Med
Food. 13 (4): 985-91 (2010)] **PEER REVIEWED** <a
...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.
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.
... 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
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
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
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
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**
REPORTED FATAL DOSE:
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. Its use in hydraulic fracturing fluids will result in its direct
release to the environment. It can also be released directly to the
environment in exhaust gases from combustion engines. Methanol has been
identified as a natural emission product from various plants and as a
biological decomposition product of biological wastes and sewage; natural
emission sources include volcanic gases, vegetation, microbes, and
insects, and methanol is a product of decaying organic material. 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 a measured Koc of 2.75.
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 its 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 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
4.6 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 in fish suggest
bioconcentration in aquatic organisms is low. Hydrolysis and photolysis
are not expected to be an important environmental fate processes since
this compound lacks functional groups that hydrolyze and photolyze 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
air, and ingestion of food and drinking water. Exposure to methanol can
occur when people use certain paint strippers, aerosol spray paints, wall
paints, windshield wiper fluid, and small engine fuel. (SRC) **PEER
REVIEWED**
PROBABLE ROUTES OF HUMAN EXPOSURE:
According to the 2006 TSCA Inventory Update Reporting data, the number of
persons reasonably likely to be exposed in the industrial manufacturing,
processing, and use of methanol is 1000 or greater; the data may be
greatly underestimated(1).[(1) US EPA; Inventory Update Reporting (IUR).
Non-confidential 2006 IUR Records by Chemical, including Manufacturing,
Processing and Use Information. Washington, DC: U.S. Environmental
Protection Agency. Available from, as of Sept 8, 2011:

NIOSH (NOES Survey 1981-1983) has statistically estimated that 1,620,617
workers (388,352 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
air, ingestion of food and drinking water(SRC).[(1) NIOSH; NOES. National
Occupational Exposure Survey conducted from 1981-1983. Estimated numbers
of employees potentially exposed to specific agents by 2-digit standard
industrial classification (SIC). Available from, as of Nov 2, 2011:
http://www.cdc.gov/niosh/ipcs/nicstart.html] **PEER REVIEWED**
Exposure to methanol can occur when people use certain paint strippers,
aerosol spray paints, wall paints, windshield wiper fluid, and small
engine fuel(1).[(1) US EPA; OPPT Chemical Fact Sheet (EPA 749-F-94-013),
Chemicals in the Environment: Methanol (CAS NO. 67-56-1). Available, as of
Sept 20, 2011: http://www.epa.gov/chemfact/f_methan.txt] **PEER REVIEWED**
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
concentrations are maintained within upper limit of 200 ppm by proper
ventilation.[Clayton, G. D. and F. E. Clayton (eds.). Patty's Industrial
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(2-4); in one study, it was detected in 3.6% of 387 expired air samples
collected from 54 volunteers at a geometric mean concentration 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 has been identified as a volatile emission product from evergreen
cypress trees(1). Methanol is formed during biological decomposition of
biological wastes, sewage, sludges and various organic compounds(2,3).
Natural emission sources include volcanic gases, vegetation, microbes, and
insects(4) and methanol is a product of decaying organic material(5).[(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) Van Aken B et al; Environ Sci Technol
38: 4572-4579 (2004) (4) Graedel TE et al; Atmospheric Chemical Compounds.
Sources, Occurrence, and Bioassay. Orlando, FL: Academic Press p. 232
(1986) (5) EPA; OPPT Chemical Fact Sheet (EPA 749-F-94-013), Chemicals in
the Environment: Methanol (CAS NO. 67-56-1). Available, as of Sept 20,

2011: http://www.epa.gov/chemfact/f_methan.txt] **PEER REVIEWED**
Methanol is found in wood.[Verschueren, K. Handbook of Environmental Data
on Organic Chemicals. Volumes 1-2. 4th ed. John Wiley & Sons. New
York, NY. 2001, p. 1425] **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**
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). Methanol's use in hydraulic fracturing fluids(2,3)
results in its direct release to the environment(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(4). Annual emission releases from methanol production,
end-product mfg, and storage/handling have been estimated to be 68, 49,
and 12 million lb, respectively(4). Methanol has been identified as
product in the exhaust of combustion engines using fuels containing
ethanol, 2-propanol, isooctane and hexane(5).[(1) English A et al; in
Kirk-Othmer Encycl Cheml Technol 4th ed Kroschwitz JI, ed. New York, NY
John Wiley and Sons 16: 537-56 (1995) (2) FracFocus; Chemical Discovery
Registry, Hydraulic Fracturing, What Chemicals are Used. Available from,
as of Sept 19, 2011:
http://fracfocus.org/chemical-use/what-chemicals-are-used (3) Saba T et
al; White Paper: Methanol Use in Hydraulic Fracturing Fluids, Methanol
Institute, August 29, 2011. Available from, as of Sept 19, 2011:
http://www.methanol.org/ (4) USEPA; Chemical Hazard Information Profiles
(CHIPS). USEPA-560/11-80-011 p. 196-7 (1980) (5) Zervas E et al; Environ
ENVIRONMENTAL FATE:
TERRESTRIAL FATE: Based on a classification scheme(1), a measured Koc
value of 2.75(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). Methanol is expected to volatilize
from dry soil surfaces(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) Schuurmann G et al; Environ Sci Technol
(supplemental material) 40: 7005-7011 (2006) (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.
EPA/600/2-89/011., Ada, OK: Robert S. Kerr Environ Res Lab (1989)] **PEER
REVIEWED**
AQUATIC FATE: Based on a classification scheme(1), a measured Koc value of
2.75(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 4.6 and 35
days, respectively(SRC). According to a classification scheme(5), a BCF of

< 10 measured in fish(6), suggests bioconcentration in aquatic organisms
is low(SRC). Methanol lacks functional groups that hydrolyze or absorb
light under environmentally relevant conditions(3), therefore hydrolysis
and photolysis are not expected to be important environmental fate
processes(SRC). Methanol has been shown to undergo rapid biodegradation in
a variety of screening studies using sewage seed and activated sludge
inoculum(7-10), which suggests that biodegradation will occur in aquatic
environments.[(1) Swann RL et al; Res Rev 85: 17-28 (1983) (2) Schuurmann
G et al; Environ Sci Technol (supplemental material) 40: 7005-7011 (2006)
(3) Lyman WJ et al; Handbook of Chemical Property Estimation Methods.
Washington, DC: Amer Chem Soc pp. 4-9, 7-4, 7-5, 8-12, 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)
(10) NITE; Chemical Risk Information Platform (CHRIP). Biodegradation and
Bioconcentration. Tokyo, Japan: Natl Inst Tech Eval. Available from, as of
Sept 16, 2011: http://www.safe.nite.go.jp/english/db.html] **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). The major degradation product from
reaction with hydroxyl radicals is formaldehyde(4).[(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)
(4) Grosjean D; J Braz Chem Soc 8: 433-442 (1997)] **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. 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. 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).[(1) Loehr RC; Treatability potential for EPA listed hazardous
wastes in soil. EPA/600/2-89/011., Ada, OK: Robert S. Kerr Environ Res Lab
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). Methanol, present at 100 mg/L,
reached 92% of its theoretical BOD in 2 weeks using an activated sludge

inoculum at 30 mg/L in the Japanese MITI test(7).[(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) (7)
NITE; Chemical Risk Information Platform (CHRIP). Biodegradation and
Bioconcentration. Tokyo, Japan: Natl Inst Tech Eval. Available from, as of
Sept 16, 2011: http://www.safe.nite.go.jp/english/db.html] **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, maintained 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 is 9.44X10-13 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 functional groups that
hydrolyze under environmental conditions(2). Methanol does not contain
chromophores that absorb at wavelengths > 290 nm(2), and therefore is
not expected to be susceptible to direct photolysis by sunlight(SRC).
Methanol in aqueous solution exhibited no degradation when exposed to
sunlight using an EPA test protocol(3). Sediment and clay suspension
solution did not photocatalyze the degradation of methanol in aqueous
solution during irradiation with UV light(4). The rate constant for the
reaction of methanol with hydroxyl radicals in aqueous solutions of
natural water is 9.7X10+8 L/mol-sec(5); this corresponds to an aquatic
half-life of about 2.5 years at an aquatic concentration of 1X10-17
hydroxyl radicals per liter(6). The rate constant for the vapor-phase
reaction of methanol with nitrate radicals is 2.1X10-16 cu cm/molecule-sec
at 25 deg C(7). This corresponds to an atmospheric half-life of about 160
days at a night-time atmospheric concentration of 2.4X10+8 nitrate
radicals per cu cm(8).[(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 Estimation Methods.
Washington, DC: Amer Chem Soc pp. 7-4, 7-5, 8-12 (1990) (3) Hustert K et
al; Chemosphere 10: 995-8 (1981) (4) Oliver BG et al; Environ Sci Technol
13: 1075-7 (1979) (5) Buxton GV et al; J Phys Chem Ref Data 17: 513-882
(1988) (6) Mill T et al; Science 207: 886-887 (1980) (7) Gramatica P et
al; Atmos Environ 37: 3115-3124 (2003) (8) Atkinson R et al; Environ Sci
Technol 19: 87-90 (1985)] **PEER REVIEWED**
ENVIRONMENTAL BIOCONCENTRATION:
Fish (golden ide (Leuciscus idus melanotus)) exposed to 0.05 mg/L of
methanol for three days in an aquatic tank had measured BCF values of less
than 10(1). According to a classification scheme(2), this BCF suggests the
potential for 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:
The measured Koc for methanol is reported to be 2.75(1). According to a
classification scheme(2), this estimated Koc value suggests that methanol
is expected to have very high mobility in soil(SRC).[(1) Schuurmann G et
al; Environ Sci Technol (supplemental material) 40: 7005-7011 (2006) (2)
Swann RL et al; Res Rev 85: 17-28 (1983)] **PEER REVIEWED**
VOLATILIZATION FROM WATER/SOIL:
The measured Henry's Law constant for methanol at 25 deg C 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 4.6
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 manufacturing 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). Concentration of
42.4 ppm detected in leachate from the Love Canal in Niagara Falls, NY(3).
Concentration 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: Average ambient concentrations 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
INDOOR: Methanol has been detected (concentration not reported) in indoor
air of residential and office buildings(1,2). In a newly constructed
house dwelling in Melbourne Australia, methanol concentrations in the
living room and bedroom areas ranged from 550-860 ug/cu m two days after
construction to 130-220 ug/cu m 246 days after construction while outdoor
air levels were < 5 ug/cu m(3).[(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) (3)
Brown SK; Indoor Air 12: 55-63 (2002)] **PEER REVIEWED**
RURAL/REMOTE: Methanol was detected at mean ambient atmospheric
concentrations of 7.9 and 2.6 ppb at two remote AZ locations during 1982
monitoring(1). Concentrations 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
(concentration 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**
Some distilled fruit spirits contain, normally, high quantities of
methanol. ...[Bindler F et al; Food Addit Contam 5(3): 343-51 (1988)]

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**
MILK CONCENTRATIONS:
ENVIRONMENTAL: Methanol was detected in 1 of 12 samples of human milk
collected from volunteers in 4 USA cities(1).[(1) Pellizzari ED et al;
Bull Environ Contam Toxicol 28: 322-8 (1982)] **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**
used as a synergist in accordance with good agricultural practice as inert
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**
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
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 continued use. Under
this pesticide reregistration program, EPA examines newer health and
safety data for pesticide active ingredients initially registered before
November 1, 1984, and determines whether the use of the pesticide does not
pose unreasonable risk in accordance to newer saftey standards, such as
those described in 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 than those on List C, and with List C containing
pesticides of greater concern than those on List D. 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/ Prevention, 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
(USEPA); U.S. National Archives and Records Administration's Electronic
Code of Federal Regulations. Available from, as of October 7, 2011:
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
(USEPA); U.S. National Archives and Records Administration's Electronic
Code of Federal Regulations. Available from, as of October 7, 2011:
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
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 (USEPA); U.S. National Archives and
Records Administration's Electronic Code of Federal Regulations. Available
from, as of October 7, 2011: 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
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]
**PEER REVIEWED**
(WI) WISCONSIN 5000 ug/L[USEPA/Office of Water; Federal-State Toxicology
REVIEWED**
FDA REQUIREMENTS:
Methyl alcohol is an indirect food additive for use only as a component of
adhesives.[21 CFR 175.105 (USFDA); U.S. National Archives and Records
as of October 7, 2011: 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 of
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 (USFDA); U.S. National Archives and Records
as of October 7, 2011: http://www.gpoaccess.gov/ecfr] **PEER REVIEWED**
ALLOWABLE TOLERANCES:
used as a solvent in accordance with good agricultural practice as inert
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:

used as a synergist in accordance with good agricultural practice as inert
growing crops only.[40 CFR 180.920; U.S. National Archives and Records
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
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. Whitehouse Station, NJ: Merck and Co., Inc.,
2006., p. 1029] **PEER REVIEWED**
COLOR/FORM:
Colorless liquid[Lewis, R.J. Sr.; Hawley's Condensed Chemical Dictionary
15th Edition. John Wiley & Sons, Inc. New York, NY 2007., p. 816]
**PEER REVIEWED**
ODOR:
Alcoholic odor; pungent odor when crude[O'Neil, M.J. (ed.). The Merck
Index - An Encyclopedia of Chemicals, Drugs, and Biologicals. Whitehouse
Station, NJ: Merck and Co., Inc., 2006., p. 1029] **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. Whitehouse Station, NJ:
Merck and Co., Inc., 2006., p. 1029] **PEER REVIEWED**
MELTING POINT:
-97.8 deg C[O'Neil, M.J. (ed.). The Merck Index - An Encyclopedia of
Chemicals, Drugs, and Biologicals. Whitehouse Station, NJ: Merck and Co.,
Inc., 2006., p. 1029] **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. Whitehouse Station, NJ: Merck and Co., Inc., 2006., p. 1029]
**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.
Whitehouse Station, NJ: Merck and Co., Inc., 2006., p. 1029] **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**
HEAT OF COMBUSTION:
726.1 kJ/mole[Haynes, W.M. (ed.) CRC Handbook of Chemistry and Physics.
91st ed. Boca Raton, FL: CRC Press Inc., 2010-2011, p. 5-68] **PEER
REVIEWED**
HEAT OF VAPORIZATION:
37.34 kJ/mole (at 25 deg C)[Haynes, W.M. (ed.) CRC Handbook of Chemistry
and Physics. 91st ed. Boca Raton, FL: CRC Press Inc., 2010-2011, p.
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
Soluble 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**
Miscible in water at 20 deg C[Flick, E.W. Industrial Solvents Handbook.
3rd ed. Park Ridge, NJ: Noyes Publications, 1985., p. 188] **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. Whitehouse
Station, NJ: Merck and Co., Inc., 2006., p. 1029] **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:
22.07 mN/m at 25 deg C[Haynes, W.M. (ed.) CRC Handbook of Chemistry and
Physics. 91st ed. Boca Raton, FL: CRC Press Inc., 2010-2011, p. 6-143]
**PEER REVIEWED**
VAPOR DENSITY:
1.11 (Air = 1)[O'Neil, M.J. (ed.). The Merck Index - An Encyclopedia of
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:
0.544 mPa sec (at 25 deg C)[Haynes, W.M. (ed.) CRC Handbook of Chemistry
OTHER CHEMICAL/PHYSICAL PROPERTIES:
Dipole moment: 1.69 /debyes/; specific heat: 0.595-0.605 at 20-25 deg C,
forms azeotropes with many compounds; burns with nonluminous bluish flame
...[O'Neil, M.J. (ed.). The Merck Index - An Encyclopedia of Chemicals,
Drugs, and Biologicals. Whitehouse Station, NJ: Merck and Co., Inc.,
2006., p. 1029] **PEER REVIEWED**
1 mg/L = 764 ppm; 1 ppm = 1.31 mg/cu m at 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: 3.215 kJ/mole[Haynes, W.M. (ed.) CRC Handbook of Chemistry
Partition 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)]
Vapor pressure = 100 mm Hg at 21.2 deg C[Lewis, R.J. Sr.; Hawley's
Condensed Chemical Dictionary 15th Edition. John Wiley & Sons, Inc.
New York, NY 2007., p. 816] **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
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**
Based on measured Henry's law constants reported in literature, the
equation that describes the Henry's law constant temperature dependence of
methanol over a temperature range of 0-80 deg C is: ln K = -12.46 +
5312.4/T where T is the absolute temperature (kelvin) and K is units of
moles/cu decimeter-atm[Warneck P; Atmospheric Environ 40: 7146-7151
CHEMICAL SAFETY & HANDLING:
DOT EMERGENCY GUIDELINES:
/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. 2012 Emergency Response
Guidebook. Washington, D.C. 2012] **PEER REVIEWED**
/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. 2012 Emergency
Response Guidebook. Washington, D.C. 2012] **PEER REVIEWED**
/GUIDE 131: FLAMMABLE LIQUIDS - TOXIC/ Public Safety: CALL Emergency
Response Telephone Number on Shipping Paper first. If Shipping Paper not
available or no answer, refer to appropriate telephone number listed on
the inside back cover. 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. 2012 Emergency Response Guidebook. Washington, D.C. 2012]
**PEER 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. 2012 Emergency
/GUIDE 131: FLAMMABLE LIQUIDS - TOXIC/ Evacuation: Spill: See Table 1 Initial Isolation and Protective Action Distances for highlighted
materials. For non-highlighted materials, increase, in the downwind
direction, as necessary, the isolation distance shown under "PUBLIC
SAFETY". 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. 2012 Emergency Response Guidebook.
Washington, D.C. 2012] **PEER 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 Fire: Dry chemical, CO2, water spray or
alcohol-resistant foam. Large Fire: 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
let fire burn.[U.S. Department of Transportation. 2012 Emergency Response
Guidebook. Washington, D.C. 2012] **PEER 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 Spill: 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 Spill: 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. 2012 Emergency
/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. In case of burns,
immediately cool affected skin for as long as possible with cold water.
Do not remove clothing if adhering to skin. Keep victim warm and quiet.
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. 2012 Emergency Response Guidebook. Washington, D.C. 2012]
**PEER 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,
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. Sr. (ed) Sax's
**PEER REVIEWED**
FIRE POTENTIAL:
Dangerous fire hazard when exposed to heat, flame or oxidizers.[Lewis,
R.J. Sr. (ed) Sax's Dangerous Properties of Industrial Materials. 11th
Edition. Wiley-Interscience, Wiley & Sons, Inc. Hoboken, NJ. 2004., p.
NFPA HAZARD CLASSIFICATION:
Health: 1. 1= Materials that, on exposure, would cause significant
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.[National Fire Protection Association; Fire Protection Guide to
Hazardous Materials. 14TH Edition, Quincy, MA 2010, 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.[National Fire Protection
Association; Fire Protection Guide to Hazardous Materials. 14TH Edition,
Quincy, MA 2010, p. 325-81] **PEER REVIEWED**
Instability: 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.[National Fire
Protection Association; Fire Protection Guide to Hazardous Materials.
14TH Edition, Quincy, MA 2010, p. 325-81] **PEER REVIEWED**
FLAMMABLE LIMITS:
Lower flammable limit: 6.0% by volume; Upper flammable limit: 36% by
volume[National Fire Protection Association; Fire Protection Guide to
Hazardous Materials. 14TH Edition, Quincy, MA 2010, 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:
52 deg F (11 deg C) (closed cup)[National Fire Protection Association;
Fire Protection Guide to Hazardous Materials. 14TH Edition, Quincy, MA
2010, p. 325-81] **PEER REVIEWED**
AUTOIGNITION TEMPERATURE:
867 deg F (464 deg C)[National Fire Protection Association; Fire
Protection Guide to Hazardous Materials. 14TH Edition, Quincy, MA 2010, p.
FIRE FIGHTING PROCEDURES:
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 containers with flooding

quantities or 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.
2005, p. 564] **PEER REVIEWED**
TOXIC COMBUSTION PRODUCTS:
Poisonous gases including formaldehyde are produced in fire.[Sittig, M.
Handbook of Toxic and Hazardous Chemicals and
Carcinogens, 2002. 4th
ed.Vol 1 A-H Norwich, NY: Noyes Publications, 2002., p. 1522] **PEER
REVIEWED**
FIREFIGHTING HAZARDS:
Vapors may travel long distances to ignition sources and flashback. Vapors
in confined areas may explode when exposed to fire.[Sittig, M. Handbook of
Toxic and Hazardous Chemicals and
Carcinogens, 2002. 4th ed.Vol 1 A-H
Norwich, NY: Noyes Publications, 2002., p. 1523] **PEER REVIEWED**
EXPLOSIVE LIMITS & POTENTIAL:
Lower explosive limit 6.0%; Upper explosive limit 36.5 %[Lewis, R.J. Sr.
(ed) Sax's Dangerous Properties of Industrial Materials. 11th Edition.
**PEER REVIEWED**
Explosive in the form of vapor when exposed to heat or flame.[Lewis, R.J.
Sr. (ed) Sax's Dangerous Properties of Industrial Materials. 11th Edition.
**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.
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. Sr. (ed) Sax's
**PEER REVIEWED**
/Acetyl bromide/ interaction with... methanol... is violent, hydropgen
bromide being evolved.
[Bretherick, L. Handbook of Reactive Che
mical
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.
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
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.
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
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
the 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.
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.
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.,

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
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
Furfuryl alcohol is hypergolic with high-strength nitric acid and methanol
has been used as a propellant fuel.[Bretherick, L. Handbook of Reactive
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
Liquid /phosphorous (III) oxide/ (above 24 deg C) reacts very violently
with methanol... and charring may occur.[Bretherick, L. Handbook of
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.
When 1 gram of sodium hydroxide was added to a mixture of 1 mL methanol
and 1 mL chloroform, an exothermic reaction occurred. Potassium hydroxide
and other alkalies may replace sodium hydroxide as a reactant.[National
Fire Protection Association; Fire Protection Guide to Hazardous
Materials. 14TH Edition, Quincy, MA 2010, p. 491-180] **PEER REVIEWED**
In mineral analysis the potassium cation is sometimes identified by adding
perchloric acid in the presence of ethyl alcohol concentration. Explosions

frequently occur that are due to the spontaneous decomposition of ethyl
perchlorate formed during concentration and of residual perchloric acid.
With methyl alcohol, the reaction is identical except that the methyl
perchlorate that is formed is very explosive.[National Fire Protection
Association; Fire Protection Guide to Hazardous Materials. 14TH Edition,
Quincy, MA 2010, p. 491-142] **PEER REVIEWED**
A flask containing a saturated solution of anhydrous lead perchlorate
dissolved in methyl alcohol exploded when it was disturbed.[National Fire
The Petrov method of preparing 1-iodo-2-ethoxy-3-butene calls for addition
of 15 grams of mercuric oxide to 0.11 molar ethyl alcohol in 25 mL of
methyl alcohol, following by 25 grams of powdered iodine at -10 to -15 deg
C, filtration, and dilution. A change in the procedure used 1 molar ethyl
alcohol. While the alcohol was being distilled off under the vacuum, a
violent explosion occurred.[National Fire Protection Association; Fire
Protection Guide to Hazardous Materials. 14TH Edition, Quincy, MA 2010, p.
A laboratory preparation of hexa-aquochromic sulfate required the
reduction of chromic anhydride by methyl alcohol. When the alcohol was
contacted by the anhydride, an explosion and fire resulted.[National Fire
HAZARDOUS DECOMPOSITION:
When heated to decomposition it emits acrid smoke and irritating
fumes.[Lewis, R.J. Sr. (ed) Sax's Dangerous Properties of Industrial
Materials. 11th Edition. Wiley-Interscience, Wiley & Sons, Inc.
Hoboken, NJ. 2004., p. 2376] **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. 2005-151 (2005)] **PEER
REVIEWED**
PROTECTIVE EQUIPMENT & CLOTHING:
Personnel protection: ... 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. 2005, p.
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
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
(APF) Respirator Recommendations APF = 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. 2005-151 (2005)] **PEER REVIEWED**
(APF) Respirator Recommendations APF = 25 Any supplied-air respirator 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
REVIEWED**
(APF) Respirator Recommendations APF = 50 Any supplied-air respirator that
has a tight-fitting facepiece and is operated in a continuous-flow mode.
APF = 50 Any self-contained breathing apparatus with a full facepiece. APF
= 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. 2005-151 (2005)] **PEER REVIEWED**
Respirator Recommendations: Emergency or planned entry into unknown
concentrations or IDLH conditions: Assigned Protection Factor (APF)
Respirator Recommendations APF = 10,000 Any self-contained breathing
apparatus that has a full facepiece and is operated in a pressure-demand
or other positive-pressure mode. APF = 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. 2005-151 (2005)] **PEER REVIEWED**
Respirator Recommendations: Escape: Any appropriate escape-type,
self-contained 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.
2005-151 (2005)] **PEER REVIEWED**
Wear appropriate personal protective clothing to prevent skin
contact.[NIOSH. NIOSH Pocket Guide to Chemical Hazards & Other
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. 2005-151 (2005)] **PEER REVIEWED**
PREVENTIVE MEASURES:
SRP: The scientific literature for the use of contact lenses by industrial
workers is inconsistent. The benefits 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**
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.
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
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
The worker should immediately wash the skin when it becomes
contaminated.[NIOSH. NIOSH Pocket Guide to Chemical Hazards & Other
REVIEWED**
Work clothing that becomes wet should be immediately removed due to its
flammability hazard (i.e., for liquids with a flash point < 100 deg
F).[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. 2005-151 (2005)] **PEER REVIEWED**
SRP: Local exhaust ventilation should be applied wherever there is an
incidence 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. Ensure
that the local ventilation moves the contaminant away from the worker.
**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. The completeness of the cleaning
procedures should be considered before the decontaminated protective
clothing is returned for reuse by the workers. Contaminated clothing
should not be taken home at the 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 November 22, 2011:
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.
STORAGE CONDITIONS:
When large amounts of methanol are stored in enclosed 14 Methanol spaces,
monitoring by means of lower explosion limit monitors is
desirable.[Fiedler E et al; Ullmann's Encyclopedia of Industrial Chemistry
7th ed. (1999-2011). NY, NY: John Wiley & Sons; Methanol. Online
Posting Date: June 15, 2000] **PEER REVIEWED**
Permanently installed fire-extinguishing equipment should be provided in
large storage facilities. Water cannons are generally installed in storage
tank farms to cool steel constructions and neighboring tanks in the event
of fire. Large tanks should have permanently installed piping systems for
alcohol-resistant fire-extinguishing foams.[Fiedler E et al; Ullmann's
Encyclopedia of Industrial Chemistry 7th ed. (1999-2011). NY, NY: John
Wiley & Sons; Methanol. Online Posting Date: June 15, 2000] **PEER
REVIEWED**
Small-Scale Storage. Fairly small amounts ( < or = 10 L) of methanol for
laboratory and industrial use are stored in glass bottles or sheet-metal
cans; amounts up to 200 L are stored and transported in steel drums. Some
plastic bottles and containers cannot be used because of their
permeability and the danger of dissolution of plasticizers. High-density
polyethylene and polypropylene are suitable, whereas poly(vinyl chloride)
and polyamides are unsuitable.[Fiedler E et al; Ullmann's Encyclopedia of
Industrial Chemistry 7th ed. (1999-2011). NY, NY: John Wiley & Sons;
Methanol. Online Posting Date: June 15, 2000] **PEER REVIEWED**
Large-Scale Storage. Large amounts of methanol are stored in tanks that
correspond in design and construction to those used for petroleum
products; cylindrical tanks with capacities from a few hundred cubic
meters to more than 100,000 cubic meters are normally used. With
fixed-roof tanks, special measures (e.g., nitrogen blanketing) should be
adopted to prevent the formation of an ignitable atmosphere in the space
above the liquid surface. Emission of methanol may occur if the level
fluctuates. To avoid these problems, large tanks are often equipped with
floating roofs; attention should therefore be paid to guard against entry
of rainwater.[Fiedler E et al; Ullmann's Encyclopedia of Industrial
Chemistry 7th ed. (1999-2011). NY, NY: John Wiley & Sons; Methanol.
Online Posting Date: June 15, 2000] **PEER REVIEWED**
Store in tightly closed containers in a cool, well ventilated area away
from heat.[Sittig, M. Handbook of Toxic and Hazardous Chemicals and
Carcinogens, 2002. 4th ed.Vol 1 A-H Norwich, NY: Noyes Publications,
2002., p. 1522] **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
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
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
Environmental considerations- Air spill: Apply water spray or mist to
knock down vapors.[Association of American Railroads; Bureau of
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 (USEPA); U.S. National Archives
and Records Administration's Electronic Code of Federal Regulations.
Available from, as of November 23, 2011: http://www.gpoaccess.gov/ecfr]
**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**
SRP: Wastewater from contaminant suppression, cleaning of protective
clothing/equipment, or contaminated sites should be contained and
evaluated for subject chemical or decomposition product concentrations.
Concentrations shall be lower than applicable environmental discharge or
disposal criteria. Alternatively, pretreatment and/or discharge to a
permitted wastewater treatment facility is acceptable only after review
by the governing authority and assurance that "pass through" violations
will not occur. Due consideration shall be given to remediation worker

exposure (inhalation, dermal and ingestion) as well as fate during
treatment, transfer and disposal. If it is not practicable to manage the
chemical in this fashion, it must be evaluated in accordance with EPA 40
CFR Part 261, specifically Subpart B, in order to determine the
appropriate local, state and federal requirements for disposal. **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
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; 2011 Threshold Limit Values for Chemical Substances and
Physical Agents and Biological Exposure Indices . Cincinnati, OH 2011, p.
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; 2011 Threshold Limit Values for
Chemical Substances and Physical Agents and Biological Exposure Indices .

Cincinnati, OH 2011, p. 104] **PEER REVIEWED**
NIOSH RECOMMENDATIONS:
Recommended Exposure Limit: 10 Hour Time-Weighted Average: 200 ppm (260
mg/cu m), skin[NIOSH. NIOSH Pocket Guide to Chemical Hazards & Other
REVIEWED**
Recommended Exposure Limit: 15 Minute 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
REVIEWED**
IMMEDIATELY DANGEROUS TO LIFE OR HEALTH:
6000 ppm[NIOSH. NIOSH Pocket Guide to Chemical Hazards & Other
REVIEWED**
OTHER STANDARDS REGULATIONS AND GUIDELINES:
Arab Republic of Egypt TWA 200 ppm (260 mg/cu m), skin[Bingham, E.;
Australia TWA 200 ppm (260 mg/cu m); STEL 250 ppm, skin[Bingham, E.;
Beligium TWA 200 ppm (260 mg/cu m); STEL 250 ppm, skin[Bingham, E.;
Denmark TWA 200 (260 mg/cu m), skin[Bingham, E.; Cohrssen, B.; Powell,
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 &
France TWA 200 (260 mg/cu m); STEL 1000 ppm (1300 mg/cu m), skin[Bingham,
REVIEWED**
Germany (DFG MAK) TWA 200 (270 mg/cu m)[Bingham, E.; Cohrssen, B.; Powell,
Hungary 50 mg/cu m; STEL 100 mg/cu m, skin[Bingham, E.; Cohrssen, B.;
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

**PEER REVIEWED**
Japan (JSOH) TWA 200 ppm (260 mg/cu m), skin[Bingham, E.; Cohrssen, B.;
The Netherlands TWA 200 ppm (260 mg/cu m), skin[Bingham, E.; Cohrssen, B.;
The Philippines TWA 200 ppm (260 mg/cu m)[Bingham, E.; Cohrssen, B.;
Poland TWA 100 ppm; STEL 300 mg/cu m, skin[Bingham, E.; Cohrssen, B.;
Russia TWA 200 ppm; STEL 5 mg/cu m, skin[Bingham, E.; Cohrssen, B.;
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
**PEER REVIEWED**
Switzerland TWA 200 ppm (260 mg/cu m); STEL 400 ppm, skin[Bingham, E.;
Thailand TWA 200 ppm (260 mg/cu m)[Bingham, E.; Cohrssen, B.; Powell,
Turkey TWA 200 ppm (260 mg/cu m)[Bingham, E.; Cohrssen, B.; Powell, C.H.;
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 Guidlines (ERPGs) for methanol: ERPG Maximum
Airborne Concentration The ERPG-1: The maximum airborne concentration
below which it is believed nearly all individuals could be exposed for up
to 1 hour without experiencing more than mild, transient adverse health
effects or without perceiving a clearly defined objectionable odor. 200
ppm The ERPG-2: The maximum airborne concentration below which it is
believed nearly all individuals could be exposed for up to 1 hour without
experiencing or developing irreversible or other serious health effects or
symptoms that could impair an individual's ability to take protective
action. 1000 ppm The ERPG-3: The maximum airborne concentration below
which it is believed nearly all individuals could be exposed for up to 1
hour without experiencing or developing life-threatening health effects.
5000 ppm [American Industrial Hygiene Association. 2010 Emergency Response
Planning Guidelines (ERPG) Workplace Environmental Exposure Level (WEEL).
American Industrial Hygiene Association Guideline Foundation. Fairfax, VA

MANUFACTURING/USE INFORMATION:
USES:
Both oil base and water base fracturing fluids are being used in the
fracturing industry. Water base, which includes alcohol-water mixtures and
low strength acids, make up the majority of treating fluids. The common
chemicals added to these fluids are polymers for viscosity development,
crosslinkers for viscosity enhancement, pH control chemicals, gel breakers
for polymer degradation following the treatment, surfactants, clay
stabilizers, alcohol, bactericides, fluid loss additives and friction
reducer. /Hydraulic fracturing/[Halliburton; Hydraulic Fracturing.
Document ID: EPA-HQ-ORD-2010-0674-1634 p.32. Available from, as of October
27, 2011:
http://www.regulations.gov/#!documentDetail;D=EPA-HQ-ORD-2010-0674-1634]
**PEER REVIEWED**
Hydraulic fracturing uses a specially blended liquid which is pumped into
a well under extreme pressure causing cracks in rock formations
underground. These cracks in the rock then allow oil and natural gas to
flow, increasing resource production. ... Chemical Name: Methanol;
Chemical Purpose: Product stabilizer and/or winterizing agent; Product
Function: Corrosion inhibitor.[FracFocus; Chemical Disclosure Registry,
Hydraulic Fracturing, How it Works; What Chemicals are Used. Available
from, as of October 28, 2011:
http://fracfocus.org/chemical-use/what-chemicals-are-used] **PEER
REVIEWED**
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 October 10, 2011:
http://npirspublic.ceris.purdue.edu/ppis/] **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. Whitehouse Station, NJ:
Merck and Co., Inc., 2006., p. 1029] **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**
/FORMER/ 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**
/FORMER/ Used on elms /Genus: Ulmus/ as injection treatment against Dutch
Elm disease. /Freers Elm Arrester/[Purdue University; National Pesticide
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
... 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
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**
MANUFACTURERS:
Air Products and Chemicals, Inc., 7201 Hamilton Blvd., Allentown, PA
18195-1501, (610) 481-6799; Industrial Chemicals Division; Production
site: Pace, FL 32571[SRI Consulting, 2010 Directory of Chemical Producers.
Menlo Park, CA. 2010, p. 711] **PEER REVIEWED**
Eastman Chemical Company, PO Box 511, Kingsport, TN 37662 (423) 229-2000;
Production site: Kingsport, TN 37662[SRI Consulting, 2010 Directory of
Chemical Producers. Menlo Park, CA. 2010, p. 711] **PEER REVIEWED**
Millenium Petrochemicals, 1515 Miller Cut-Off Road, La Porte, TX 77571,
(713)209-7000; Production site: LaPorte, TX 77571[SRI Consulting, 2010
Directory of Chemical Producers. Menlo Park, CA. 2010, p. 711] **PEER
REVIEWED**
Praxir Inc., 39 Old Ridgebury Rd., Danbury, CT 06810-5113, (203) 837-2000;
Production site: Geismar, LA 70734[SRI Consulting, 2010 Directory of
Chemical Producers. Menlo Park, CA. 2010, p. 711] **PEER REVIEWED**
Terra Industries Inc., Terra Centre, 600 Fourth St., Sioux City, IA 51101,
(712) 277-1340; Production sites: Beaumont, TX 77704; Woodward, OK
73801[SRI Consulting, 2010 Directory of Chemical Producers. Menlo Park,
CA. 2010, p. 711] **PEER REVIEWED**
Methanol - Company and Production Data (2006)Company Site City State Zip
Manufacture Import 3M 3M Decatur Decatur AL 35609-2206 Yes No 3M 3M
Greenville Film Plant Greenville SC 29605 Yes No Azko Nobel Coatings Inc.
Azko Nobel Coatings - Saco Adhesives High Point NC 27261 No Yes BASF
Corporation BASF Corp - Corporate Headquarters Florham Park NJ 07932 No
Yes Baker Petrolite Corporation Baker Petrolite Corp - Sugar Land Sugar
Land TX 77487-5050 No Yes Bayer CropScience LP Bayer CropScience Hawthorn Kansas City MO 64120 No Yes Celanese Ltd. Celanese - Calvert City
Plant Calvert City KY 42029 Yes No Celanese Ltd. Celanese - Pampa Plant
Pampa TX 79066 Yes No Celanese Ltd. Celanese - Clear Lake Plant Pasadena
TX 77507 Yes No Chevron North America Products Chevron - Port Arthur
Lubricants Plant Port Arthur TX 77641 Yes No Ciba Specialty Chemicals
Corp. Ciba Specialty Chems - Newport Newport DE 19804 Cognis Corporation
Cognis Oleochemicals L.L.C. Cincinnati OH 45232-1419 Croda Inc. Croda
Uniqema Inc. (Atlas Point Plant) New Castle DE 19720 Yes No Cytec
Industries Inc. Cytec Industries Inc. - Willow Island Willow Island WV
26134 DAK Americas LLC DAK Americas - Cape Fear Leland NC 28451 Yes No
DIC International (USA) LLC DIC - Glenpointe Centre West Teaneck NJ 07666
Degussa Corporation Degussa Corp - Parsippany Parsippany NJ 07054 No Yes
Domtar, Inc. Domtar Maine Corp. Baileyville ME 04694 No Yes DuPont Teijin
Films US LP DuPont Teijin Films - Cedar Creek Plant Fayetteville NC 28312
DuPont Teijin Films US LP DuPont Teijin Films - Hopewell Plant Chester VA
23831 Yes No DuPont Teijin Films US LP DuPont Teijin Films - Florence
Plant Florence SC 29501-0543 DuPont Teijin Films US LP DuPont Teijin
Films - Old Hickory Plant Old Hickory TN 37138 Yes No DynaChem Inc.
DynaChem Inc. Georgetown IL 61846 Yes No E. I. du Pont de Nemours and
Company Dupont - Headquarters (imported centrally through broker)
Wilmington DE 19898 No Yes E. I. du Pont de Nemours and Company Dupont Cooper River Plant Moncks Corner SC 29461 Yes No E. I. du Pont de Nemours
and Company Dupont - La Porte Plant La Porte TX 77571 Yes No E. I. du Pont
de Nemours and Company Dupont - Kinston Plant Kinston NC 28502-0800 E.
I. du Pont de Nemours and Company Dupont - Old Hickory Plant Old Hickory
TN 37138 Yes No Eastman Chemical Company Carolina Eastman Division
Columbia SC 29169 Yes No Eastman Chemical Company Tennessee Eastman
Division Kingsport TN 37660 Yes Yes Eastman Chemical Company Texas Eastman
Division Longview TX 75603 Yes No Eastman Kodak Company Eastman Kodak Park
Rochester NY 14650 Yes No Fisher Scientific Company, L.L.C. Fisher
Chemical Bridgewater Packaging Facility Bridgewater NJ 08876 No Yes GE
Plastics Mt.Vernon, Inc. GE Plastics Mt.Vernon, Inc. Mt. Vernon IN
47620-9367 Yes No General Motors Corporation Renaissance Center General
Motors Corporation Renaissance Center Detroit MI 48243-7301 No Yes HD
MicroSystems, LLC HD MicroSystems, LLC CA CA 95014 No Yes Hexion Specialty
Chemicals, Inc. Hexion Specialty Chems - Sheboygan Sheboygan WI 53081 No
Yes Hexion Specialty Chemicals, Inc. Hexion Specialty Chems - # 40031
Portland Portland OR 97203 No Yes Hexion Specialty Chemicals, Inc. Hexion
Specialty Chems - Acme Riegelwood NC 28456 No Yes Hexion Specialty
Chemicals, Inc. Hexion Specialty Chems - Missoula Missoula MT 59808 No Yes
INVISTA S.a r.l. INVISTA - La Port Facility La Porte TX 77571 Yes No
INVISTA S.a r.l. INVISTA - Spartanburg Facility Spartanburg SC 29307 Yes
No [US EPA; Inventory Update Reporting (IUR). Non-confidential 2006 IUR
Records by Chemical, including Manufacturing, Processing and Use
Information. Washington, DC: U.S. Environmental Protection Agency.
Available from, as of Sept 8, 2011:
Methanol - Company and Production Data (2006) Company Site City State Zip
Manufacture Import LANXESS Corporation LANXESS - Wellford Wellford SC
29385 LaPorte Methanol Company, L.P. La Porte Methanol Plant La Porte TX
77571 Yes No Lonza, Inc. Lonza - Mapleton Mapleton IL 61547 Yes No Lonza,
Inc. Lonza - Williamsport Williamsport PA 17701 Yes No Lynx Chemical
Group, LLC Lynx Chemical - Columbus Plant Columbus GA 31904 Yes No
Mitsubishi Gas Chemical America, Inc. Mitsubishi Gas Chemical America,
Inc. New York NY 10017 No Yes Mitsui & Co. (USA) Inc. Mitsui & Co Houston Houston TX 77056 No Yes Nippon Paint (USA) Inc. Nippon Paint (USA)
Inc. d/b/a Nippon Paint (America) Corp. Teaneck NJ 07666 No Yes Nissan
Chemical Houston Corporation Nissan Chemical Houston Corporation Pasadena
TX 77507-1308 Yes No Nova Molecular Technologies, Inc. Nova Molecular
Technologies, Inc. Pasadena TX 77507 Yes No Oxy Vinyls, LP Oxy Vinyls Deer Park Chlor-Alkali Deer Park TX 77536 No Yes Pioneer Plastics
Corporation Pioneer Plastics Corp - Auburn Auburn ME 04211 No Yes Potlatch
Corporation Potlatch Forest Products Corporation Arkansas City AR 71630 No
Yes Praxair, Inc. Praxair - Geismar Geismar LA 70734 Yes No SNF Holding
Company SNF Holding Co - Flocryl Inc - Acrylates Divison Riceboro GA 31323
Yes No Safety-Kleen Systems, Inc. Safety-Kleen Systems, Inc. Plano TX
75024 No Yes Shell Trading (US) Company Shell Trading (US) Company, Main
office Houston TX 77010 No Yes Solutia Inc. Solutia - Indian Orchard Plant
Springfield MA 01151 Southern Chemical Corporation Southern Chemical
Corporation Houston TX 77068 No Yes Sunoco, Inc. Sunoco - Marcus Hook
Refinery Marcus Hook PA 19061 Yes No Terra Industries, Inc. Terra
International (Oklahoma) Inc. Woodward OK 73801 Yes No The Procter &
Gamble Company Procter & Gamble Mfg. Co - Sacramento Sacramento CA 95813
Yes No The Valspar Corporation The Valspar Corporation Minneapolis MN
55415 No Yes Ticona Ticona Shelby Site Grover NC 28073 Yes No Ticona
Ticona Bishop Bishop TX 78343 Yes No Toray Plastics (America), Inc. Toray
Plastics (America) - Quonset Point North Kingstown RI 02852 Yes No Twin
Rivers Technologies Twin Rivers Technologies - Natural Ingredients
Cincinnati OH 45232 Yes No Ulrich Chemical, Inc. Ulrich Chemical, Inc Louisville Louisville KY 40216 Yes No Ulrich Chemical, Inc. Ulrich
Chemical, Inc - Indianapolis Indianapolis IN 46226 Yes No Univar USA Inc.
Univar USA Inc - Redmond Redmond WA 98052 No Yes [US EPA; Inventory Update
Reporting (IUR). Non-confidential 2006 IUR Records by Chemical, including
Manufacturing, Processing and Use Information. Washington, DC: U.S.
Environmental Protection Agency. Available from, as of Sept 8, 2011:
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**
Methanol is currently produced on an industrial scale exclusively by
catalytic conversion of synthesis gas. Processes are classified according
to the pressure used: 1) High-pressure process 25 - 30MPa 2)
Medium-pressure process 10 - 25MPa 3) Low-pressure process 5 10MPa.[Fiedler E et al; Ullmann's Encyclopedia of Industrial Chemistry 7th
ed. (1999-2011). NY, NY: John Wiley & Sons; Methanol. Online Posting
Date: June 15, 2000] **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
GENERAL MANUFACTURING INFORMATION:
Up until 2001, methanol had some use as a base fluid in hydraulic
fracturing applications (base fluid meaning methanol was the main
component in the fluid rather than water), but this use appears to be
infrequent currently due to safety handling considerations (flammability)
and much higher cost (3 to 4 times more expensive than water-based
fluids); in current water-based fracking fluids, methanol acts as a
corrosion and scale inhibitor (prevents corrosion of pipes) and friction
reducer, and methanol enhances the removal of formation water to allow the
natural gas to flow through the well.[Saba T et al; White Paper: Methanol
Use in Hydraulic Fracturing Fluids, Methanol Institute, August 29, 2011.
Available from, as of Sept 19, 2011: http://www.methanol.org/] **PEER
REVIEWED**
Companies add methanol to paint strippers, aerosol spray paints, wall
paints, carburetor cleaners, and car windshield washer products; methanol
is also a gasoline additive and, in some cases, a gasoline substitute for
use in automobiles and other small engines.[USEPA; OPPT Chemical Fact
Sheet (EPA 749-F-94-013), Chemicals in the Environment: Methanol (CAS NO.
67-56-1). Available, as of Sept 20, 2011:
http://www.epa.gov/chemfact/f_methan.txt] **PEER REVIEWED**
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
chloride 1.4%[O'Neil, M.J. (ed.). The Merck Index - An Encyclopedia of
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:
Methanol for Laboratory Use. Methanol is available commercially in various
purity grades for fine chemicals: 1) "Synthesis" quality (corresponding to

normal commercial methanol); 2) Certified analytical quality; and 3)
Extremely pure qualities for semiconductor manufacture.[Fiedler E et al;
Ullmann's Encyclopedia of Industrial Chemistry 7th ed. (1999-2011). NY,
NY: John Wiley & Sons; Methanol. Online Posting Date: June 15, 2000]
**PEER REVIEWED**
Commercial Methanol. In addition to laboratory grades, commercial methanol
is generally classified according to ASTM purity grades A and AA. Methanol
for chemical use normally corresponds to Grade AA.[Fiedler E et al;
**PEER REVIEWED**
Federal Specifications for pure methanol in the United States Property
Grade A Grade AA Ethanol content, mg/kg
< 10 Acetone content, mg/kg
< 20 Total acetone and aldehyde content, mg/kg < 30 < 30 Acid
content (as acetic acid), mg/kg < 30 < 30 Color index (APHA) < 5
< 5 Sulfuric acid test (APHA) < 30 < 30 Boiling point range (101.3
kPa), must include 64.6 + or - 0.1 deg C < 1 < 1 Dry residue, mg/L
< 10 < 10 Density (20 deg C), g/cu cm) 0.7928 0.7928 Permanganate
number > 30 > 30 Methanol content, wt% > 99.85 > 99.85 Wate
content, wt% < 0.15 < 0.10 Odor typical, non-persistent [Fiedler E et
al; Ullmann's Encyclopedia of Industrial Chemistry 7th ed. (1999-2011).
NY, NY: John Wiley & Sons; Methanol. Online Posting Date: June 15,
Grade: Technical, CP (99.85%), electronic (used to clean and dry
components), fuel[Lewis, R.J. Sr.; Hawley's Condensed Chemical Dictionary
**PEER REVIEWED**
Formaldehyde; intrastate fungicide; 37.0% formaldehyde, 15.0% methyl
alcohol.[Purdue University; National Pesticide Information Retrieval
Wilbur-Ellis Smut-Guard; fungicide; 37.0% formaldehyde, 12.0% methyl
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
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
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
Freer Elm Arrester; fungicide; 0.12% mercuric chloride, 96.65% methyl

Eureka Products Criosine Disinfectant;
disinfectant/bacteriocide/germicide; 47.6% methyl alcohol, 0.86%
nitrobenzene, 0.54% butyl 4-hydroxybenzoate, 30.0% phenol.[Purdue
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:
In addition to water, typical impurities include acetone (which is very
difficult to separate by distillation) and ethanol.[Fiedler E et al;
**PEER REVIEWED**
Grade A) acetone and aldehydes 30 ppm max; acetic acid 30 ppm max: water
content 1500 ppm max; Grade AA) acetone and aldehydes 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: 409 (1981)]
**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
billion 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**
Approximately 70% of the methanol produced worldwide is used in chemical
syntheses: in order of importance formaldehyde, methyl tertbutyl ether
(MTBE), acetic acid, methyl methacrylate, and dimethyl
terephthalate.[Fiedler E et al; Ullmann's Encyclopedia of Industrial
Chemistry 7th ed. (1999-2011). NY, NY: John Wiley & Sons; Methanol.
Online Posting Date: June 15, 2000] **PEER REVIEWED**
U. S. PRODUCTION:
(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**
**PEER REVIEWED**
(1992)8.08 billion lb[Chem & Engineering News 72 (15): 13 (4/11/94)]
**PEER REVIEWED**
**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**
**PEER REVIEWED**
**PEER REVIEWED**
**PEER REVIEWED**
**PEER REVIEWED**
Methanol is listed as a High Production Volume (HPV) chemical (65FR81686).

Chemicals listed as HPV were produced in or imported into the U.S. in
> 1 million pounds in 1990 and/or 1994. The HPV list is based on the
1990 Inventory Update Rule. (IUR) (40 CFR part 710 subpart B;
51FR21438).[EPA/Office of Pollution Prevention and Toxics; High Production
Volume (HPV) Challenge Program. Methanol (67-56-1). Available from, as of
October 11, 2011: http://www.epa.gov/hpv/pubs/general/opptsrch.htm] **PEER
REVIEWED**
Production volumes for non-confidential chemicals reported under the
Inventory Update Rule. Year Production Range (pounds) 1986 > 1 billion
1990 > 1 billion 1994 > 1 billion 1998 > 1 billion 2002 > 1
billion [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 October 11, 2011:
http://www.epa.gov/oppt/iur/tools/data/2002-vol.html] **PEER REVIEWED**
Production volume for non-confidential chemicals reported under the 2006
Inventory Update Rule. Chemical: Methanol. Aggregated National Production
Volume: 1 billion pounds and greater.[US EPA; Non-Confidential 2006
Inventory Update Reporting. National Chemical Information. Methanol
(67-56-1). Available from, as of October 11, 2011:
http://cfpub.epa.gov/iursearch/index.cfm?s=chem&err=t] **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,
P.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
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
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
ANALYTIC LABORATORY METHODS:

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 October 12, 2011: 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 October 12, 2011:
http://www.nemi.gov] **PEER REVIEWED**
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
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 October 12, 2011: 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. Methanol
http://www.osha.gov/dts/sltc/methods/toc.html] **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**
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
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
decomposition 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
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)]
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, as of July 20, 2005:
http://cerhr.niehs.nih.gov/news/methanol/methanol_final.pdf]
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]
European Chemicals Bureau; IUCLID Dataset, Methanol (67-56-1) (2000 CD-ROM
edition).[Available from, as of July 15, 2005:
http://esis.jrc.ec.europa.eu/]
HISTORY AND INCIDENTS:
... Mass poisoning involving 372 men who had consumed a soln of 82%
methanol and 18% isopropanol /was reported/.[O'Donoghue, J.L. (ed.).
Neurotoxicity of Industrial and Commercial Chemicals. Volume II. Boca
Raton, FL: CRC Press, Inc., 1985., p. 82] **PEER REVIEWED**
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
...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
SYNONYMS AND IDENTIFIERS:
RELATED HSDB RECORDS:
1646 [FORMIC ACID] (metabolite)
3915 [ASPARTAME] (metabolic precursor)
SYNONYMS:
Coat-B1400[Purdue University; National Pesticide Information Retrieval
Surflo-B17[Purdue University; National Pesticide Information Retrieval
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
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**
Caswell no 552 **PEER REVIEWED**
X-Cide 402 Industrial Bactericide[Purdue University; National Pesticide
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

1996., p. 2174] **PEER REVIEWED**
Ideal Concentrated Wood Preservative[Purdue University; National Pesticide
Wilbur-Ellis Smut-Guard[Purdue University; National Pesticide Information
Freers Elm Arrester[Purdue University; National Pesticide Information
Manhattan spirits[WHO; Environ Health Criteria 196: Methanol p.10 (1997).
http://www.inchem.org/documents/ehc/ehc/ehc196.htm]
METANOLO (ITALIAN)[Lewis, R.J. Sax's Dangerous Properties of Industrial
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://esis.jrc.ec.europa.eu/]
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
Methyl hydrid[European Chemicals Bureau; IUCLID Dataset, Methanol
Methyl hydrate[European Chemicals Bureau; IUCLID Dataset, Methanol
METHYL HYDROXIDE[Lewis, R.J. Sax's Dangerous Properties of Industrial
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
MONOHYDROXYMETHANE[Lewis, R.J. Sax's Dangerous Properties of Industrial
1996., p. 2174] **PEER REVIEWED**
Eureka Products, Criosine[Purdue University; National Pesticide

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
1996., p. 2174] **PEER REVIEWED**
WOOD ALCOHOL[Lewis, R.J. Sax's Dangerous Properties of Industrial
1996., p. 2174] **PEER REVIEWED**
WOOD NAPHTHA[Lewis, R.J. Sax's Dangerous Properties of Industrial
1996., p. 2174] **PEER REVIEWED**
WOOD SPIRIT[Lewis, R.J. Sax's Dangerous Properties of Industrial
1996., p. 2174] **PEER REVIEWED**
USEPA/OPP Pesticide Code: 053801[U.S. Environmental Protection
Agency/Office of Pesticide Program's Chemical Ingredients Database on
Methanol (67-56-1). Available from, as of October 10, 2011:
http://npirspublic.ceris.purdue.edu/ppis/] **PEER REVIEWED**
FORMULATIONS/PREPARATIONS:
Methanol for Laboratory Use. Methanol is available commercially in various
purity grades for fine chemicals: 1) "Synthesis" quality (corresponding to
normal commercial methanol); 2) Certified analytical quality; and 3)
Extremely pure qualities for semiconductor manufacture.[Fiedler E et al;
**PEER REVIEWED**
Commercial Methanol. In addition to laboratory grades, commercial methanol
is generally classified according to ASTM purity grades A and AA. Methanol
for chemical use normally corresponds to Grade AA.[Fiedler E et al;
**PEER REVIEWED**
Federal Specifications for pure methanol in the United States Property
Grade A Grade AA Ethanol content, mg/kg
< 10 Acetone content, mg/kg
< 20 Total acetone and aldehyde content, mg/kg < 30 < 30 Acid
content (as acetic acid), mg/kg < 30 < 30 Color index (APHA) < 5
< 5 Sulfuric acid test (APHA) < 30 < 30 Boiling point range (101.3
kPa), must include 64.6 + or - 0.1 deg C < 1 < 1 Dry residue, mg/L
< 10 < 10 Density (20 deg C), g/cu cm) 0.7928 0.7928 Permanganate
number > 30 > 30 Methanol content, wt% > 99.85 > 99.85 Wate
content, wt% < 0.15 < 0.10 Odor typical, non-persistent [Fiedler E et
al; Ullmann's Encyclopedia of Industrial Chemistry 7th ed. (1999-2011).
NY, NY: John Wiley & Sons; Methanol. Online Posting Date: June 15,
Grade: Technical, CP (99.85%), electronic (used to clean and dry
components), fuel[Lewis, R.J. Sr.; Hawley's Condensed Chemical Dictionary
**PEER REVIEWED**
Formaldehyde; intrastate fungicide; 37.0% formaldehyde, 15.0% methyl

Wilbur-Ellis Smut-Guard; fungicide; 37.0% formaldehyde, 12.0% methyl
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
Surflo-B17; microbicide/microbisat general; 32.37% formaldehyde, 10.5%
methyl alcohol, 10.0% alkyl dimethyl benzyl ammonium chloride.[Purdue
REVIEWED**
Coat-B1400; solution ready to use; 25.0% methyl alcohol, 24.0% morpholine
polyethoxyethanol.[Purdue University; National Pesticide Information
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
Freer Elm Arrester; fungicide; 0.12% mercuric chloride, 96.65% methyl
Eureka Products Criosine Disinfectant;
disinfectant/bacteriocide/germicide; 47.6% methyl alcohol, 0.86%
nitrobenzene, 0.54% butyl 4-hydroxybenzoate, 30.0% phenol.[Purdue
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: 20120426
LAST REVIEW DATE: Reviewed by SRP on 1/19/2012
UPDATE HISTORY:
Field Update on 2014-12-05, 2 fields added/edited/deleted
Complete Update on 2012-04-26, 1 fields added/edited/deleted
Complete Update on 02/14/2003, 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.


Field update on 12/10/1992, 1 field added/edited/deleted.
Field update on 01/28/1991, 1 field 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

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The following information was generated from the

Hazardous Substances Data Bank (HSDB),

HUMAN HEALTH EFFECTS:

suggest that methanol is a carcinogen ... The inhalation of methanol by

undetectable to 49 mg/dL and undetectable to 48 mg/dL, respectively.

/HUMAN EXPOSURE STUDIES/ The minimal lethal dose of methanol in humans

/HUMAN EXPOSURE STUDIES/ ...The charts of the patients/treated in the same

blindness, changes in color perception, double vision, and general visual

/SIGNS AND SYMPTOMS/ Chronic poisoning from repeated exposure to methanol

injuries in acute methanol poisoning: putamen and white matter necrosis

as of July 20, 2005:

resulted in 46 definite cases of methanol intoxication and 3 deaths.

(2004)] **PEER REVIEWED** <a

significant difference in mean pH in the first arterial blood gas of

2) documented route of exposure. Exclusion criteria were unknown, dermal,

Available from, as of July 20, 2005:

recipients, a kidney recipient, was discharged at 6 wk with

The aforementioned medical examinations should be repeated on an annual

workers (388,352 of these are female) are potentially exposed to methanol

intended as an educational aid only. All treatments or procedures are intended

bradykinesia) and blindness.

requiring ADH inhibition. In patients who receive ADH

c) ETHANOL: Ethanol is given to maintain a serum ethanol

toxicologist in cases of severe poisonings, in cases

may need to examine the area if irritation or pain

Philadelphia, Pennsylvania 1999., p. 1179] **PEER REVIEWED**

or ethanol should be continued until the methanol concentration is less

effective in the treatment of methanol-poisoned patients.[Megarbane B et

coma and death. Nearly all of the available information on methanol

al; J Appl Toxicol 20 (3): 239-43 (2000)] **PEER REVIEWED** <a

from, as of July 14, 2005:

Elevated serum glutamic pyruvate transaminase and alkaline phosphatase

that methanol is carcinogenic to mouse skin. In an experiment using four

malformations, and there was evidence of a positive interaction between

(NCAMs) arising from methanol exposure were observed in neonatal

196: Methanol p.86 (1997). Available from, as of July 18, 2005:

al; Neurotoxicol Teratol 26 (5): 639-50 (2004)] **PEER REVIEWED** <a

craniofacial dysmorphology. ...Dysmorphogenesis, cell death, cell cycle

gestational days 15 to 17 or 17 to 19. The animals were allowed to

methanol/kg by gavage exhibited an altered response in an operant

decrease in striatal dopamine levels was also observed in the FD group at

DNA-repair test using various strains of E. coli WP2 and in a forward

Methanol (67-56-1) (2000 CD-ROM edition). Available from, as of July 19,

activity and ATP concentrations have been shown to be selectively reduced

evaluated by separate bioassays. Ninety-six-hour bioassays in the

LD50 Hamster ip 8555 mg/kg bw[European Chemicals Bureau; IUCLID Dataset,

Chemicals to Fathead Minnows (Pimephales Promelas). Superior, WI: Center

LC50; Species: Lepomis macrochirus (Bluegill); Conditions: flow through;

LC50; Species: Helisoma trivolvis (aquatic mollusk); Concentration:

table/[WHO; Environ Health Criteria 196: Methanol p.116 (1997). Available

Crangon crangon (Brown shrimp) adult; Conditions: seawater,

LC50; Species: Crangon crangon (Brown shrimp) adult; Conditions:

Expert Panel Report on the Reproductive and Developmental Toxicity of

by animals was eliminated in expired

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

to 10 g/kg) excreted 0.1

Following a 2 mL/kg oral dose of methanol to rabbits, 5.3% was excreted in

throughout breeding and pregnancy. Blood methanol at 30 min postexposure

In addition to neurofunctional changes, bioenergetic and morphological

Based on the literature and our pilot studies, 0, 2, or 3 g/kg methanol

Environmental Health and Toxic Exposures. Second edition. Lippincott

industrial solvent, 2-methoxyethanol (2ME), enhanced teratogenicity in

(2004)] PEER REVIEWED <a

Philadelphia, Pennsylvania 1999., p. 1179] PEER REVIEWED

al; J Appl Toxicol 20 (3): 239-43 (2000)] PEER REVIEWED <a

al; Neurotoxicol Teratol 26 (5): 639-50 (2004)] PEER REVIEWED <a

Ltd., 1990, p. 174] PEER REVIEWED

1990, p. 1323] PEER REVIEWED

Microanalysis of Alcohol in Blood & Urine By Direct-Injection

Information Retrieval System (1988)] PEER REVIEWED