Methanol Basics http://www.epa.gov/orcdizux/07-meoh.htm

EPA400-F-92-009 August 1994 Fact Sheet OMS-7

Methanol Basics

What is Methanol?

Methanol is the simplest alcohol, containing one carbon atom. It is a colorless, tasteless liquid with a very faint odor and is commonlyknown as "wood alcohol."

H h

H CHgOH

Methanol is one ofa number offuels that could substitute for gasoline or diesel fuel in passenger cars, light trucks, and heavy-duty trucks and buses.

Why Consider Methanol?

Methanol's physicaland chemical characteristics result in several inherent advantages as an automotive fuel:

LOW POLLUTION

Emissionsfrom methanol cars are low in reactive hydrocarbons (which form smog) and in toxic compounds. Methanol-fueled trucks and buses emit almost no particulate matter (which cause smoke and odor, and can also be carcinogenic), and muchless nitrogen oxides than their diesel-fiieled counterparts.

FUEL SUPPLY OPTIONS

Methanol can be manufactured from a variety ofcarbon-based feedstocks such as natural gas, coal, and biomass(e.g., wood). Use ofmethanolwould diversify the country's fuel supply and reduce its dependence on imported petroleum.

FIRE SAFETY

Methanol is much less flammable than gasoline and results in less severe fires when it does ignite.

HIGH PERFORMANCE

Methanol is a high-octane fuel that offers excellent acceleration and vehicle power.

ECONOMICALLY ATTRACTIVE

Witheconomiesofscale, methanol could be produced, distributed, and sold to consumers at prices competitive with gasoline.

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Current Methanol Uses

Because of its outstanding performance and fire safety characteristics, methanol is the only fuel used in Indianapolis-type race cars. Following a series of methanol vehicle development and demonstration programs throughout the 1980's, a limited number of methanol passenger cars and buses are now commercially available. There are approximately 14,000 methanol passenger cars in use, mostly in Federal and private fleets, and about 400 methanol buses in daily operation, mostly in California.

Methanol is used in a number ofconsumer products, including paint strippers, duplicator fluid, model airplane fuel, and dry gas. Most windshield washer fluids are 50 percent methanol.

Is Methanol Poisonous?

Yes. As with many other fuels, methanol can be highly toxic and should never be taken orally. A few teaspoons ofmethanol can cause blindness and a few tablespoons can be fatal, if the exposure is not treated.

It should be noted that the human body can metabolize and eliminate low concentrations of methanol with no ill effects. (Methanol is present in many cooked vegetables, andthe artificial sweetener in diet soft drinksbreaks down into methanol during digestion.) Methanol becomes poisonous only when it overwhelms the body's capacity to remove it. Toxic effects do not occur until several hours after exposure. Effective antidotes to methanol poisoning are readily available and can be administered during this interim period.

For More Information:

The Office ofMobile Sources is the national center for research and policy on air pollution from highway and off-highway motor vehicles and equipment. You can write to us at theEPANational Vehicle and Fuel Emissions Laboratory, 2565 Plymouth Road, Ann Arbor, MI 48105. Our phone number is (734) 214-4333.

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J.

Methanol

Pharmacology: Methanol (methyl alcohol) is produced from the distillation ofwood and is a clear, colorless, volatile liquid with a weak odor that is somewhat sweeter than ethanol. Methanol is used in the industrial production of many synthetic organic compounds and is a constituent of many commercially available solvents. Products that are available in the home that contain methanol include: windshield wiperfluids and de-icers, antifreeze, glass cleaner, canned heat, paints, varnishes, paint thinners and removers. It can also be used in gasohol, which could present problemsas people try to siphon the gas by mouth and accidentally ingest some. Methanol is a natural fermentation product and its concentration may be up to 300 mg/L in wine, and even higher in other spirits.

Methanol is well absorbed from the gastrointestinal tract mucosa as well as through the skin and lungs. Both inhalation and transdermal exposure can result in toxicity. The exact lethal dose for a human is not known. Doses as low as 25 cc of40% methanol have been reported as causing toxicity. In other cases doses up to 500 cc have occurred with no side effects. Most sources consider the minimal lethal dose to be around 100 cc (1 g/kg). Poisoning with methanol may be accidental or intentional. There have been epidemics of methanol toxicity in cases where illicit whiskey has been sold to large populations or when the less expensive methanol was substituted for ethanol in drinks.

Once methanol is absorbed it is rapidly distributed in the body water with peak blood levels occurring in about 30 to 90 minutes after exposure. Ifethanol is not present 2-5% ofthe methanol is excreted unchanged by the kidneys and a small amount is eliminated by the lungs. At low blood levels the half-life ofmethanol is 2-3 hours. Once the blood levels rise above 300 mg/dl, the enzymes that metabolize methanol become saturated and the elimination half-life increases to 27 hours. When this happens a greater amount ofthe methanol is eliminated unchanged by the lungs and the kidneys. During therapy with ethanol the half-life ofmethanol becomes 30-52 hours.

Methanol itselfmay cause inebriation but by itselfin almost completely non-toxic. The methanol is metabolized by alcohol dehydrogenase to formaldehyde and then to formic acid. Clinical findings correlate better with formic acid levels than with methanol levels. It is these two metabolites that cause toxicity with formic acid being more responsible. It is the formic acid that causesthe profound metabolic acidosis that is typical ofmethanol poisoning. The overall mortalityofmethanol poisoning is approximately 20% and among survivors the rate of permanent visual impairment is 20-25%).

Clinical Presentation: The presentation within the first 1-2 hours may be similarto ethanol intoxication inthat the patient may have drowsiness, vertigo, and uninhibited behavior. There is typically a delay of the toxic symptoms anywhere from six-30 hours and longer if ethanol has been co-ingested. In casesof methanol ingestiona lack ofsymptoms early on does not meanthat the patient has not ingested a toxic amount ofmethanol.

Aside from the symptoms ofintoxication patients may also present with gastrointestinal symptoms due to acute gastritis or pancreatitis. The gastritis may be severe and is occasionally hemorrhagic. Symptoms include anorexia, severe abdominal pain, vomiting, diarrhea, increased transaminases or increased amylase. Early visual disturbances are the classic findings that are associated with methanol intoxication and include decreased vision or blurred vision. Patients may complain ofa 'snowstorm' in front ofthe eyes or photophobia. The pupils may be fixed and dilated with the funduscopic exam revealing retinal edema with hyperemiaofthe optic disc. In severe cases there may be papilledema and engorged retinal vessels. Other complications ofsevere methanol intoxication include coma, seizures, blindness, oliguric renal failure, cardiac failure, and pulmonary edema. Death may be rapid or may occur several hours after coma.

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Deathis associated with inspiratory apnea, terminal opisthotonos and convulsions.

Diagnosis: Patients who present early intheircourse withknowledge that they accidentally or intentionally ingested methanol present little difficulty. Those that cannot or will not provide an complete history as to their possible ingestion areclearly more difficult. Thesymptoms andphysical signs are non-specific. Thepatient may havea faint odor of methanol on the breathbut this can easily be missed. Ocular findings arethe most specific physical findings andare important diagnostically. Theocular physical findings or complaints inaddition to a severe metabolic acidosis as well as a high osmolar gap canjustify a presumptive diagnosis ofmethanol poisoning. The literature does contain caseswhere severe methanol intoxication hasbeenpresent but no anion gap metabolic acidosis was found (Palmisano et al. 1987). Themajority ofpatients reviewed had high ethanol levels which appeared to limited the formation of formic acid. Thus, it is important to be aware that a patient who presents with methanol exposure may havedelayed clinical and laboratoryfindings even if there was a large ingestionofmethanol.

Treatment: As with any poisoned patient the initial managementincludes close attention to adequate airway, ventilation, and perfusion. Ifthe patient is seen early, gastric lavage to remove any residual gastric methanol should be done. Ifthere is exposure to the skin, then decontamination should be done. Syrup ofipecac is not recommended as the mental status may rapidly deteriorate and there is a significant risk ofaspiration. Activated charcoal has not been proven to absorb ethanol to any extent and these studieshave been presumed to apply to methanol. Also, because alcoholstend to be consumed in large amounts and are rapidly absorbed there does not appear to be any benefit. Therefore, ifthere is no concern ofcoingestion with other toxic substances there is probably little indication for charcoal.

Labs should be sent immediately for CBC, chem 7, LFT's, amylase, U/A, serum osmolality, and methanol level. Therapy should not be withheld pending the resultsofmethanol levelifthere is a high suspicion of methanol intoxication. It may be appropriate to send ethanol and ethyleneglycol levels.

Ultimately, when treating methanolintoxication there are three major modalities to use:

(1) decrease the metabolicdegradation ofthe methanol to its toxic degradation products

(2) dialysis to increasethe removalofboth the methanol and the toxic intermediates

(3) alkalinization to counteract the severe metabolicacidosis.

** Ethanol is used to decrease the metabolism ofmethanol. Alcohol dehydrogenase acts within the liver to break down both ethanol and methanol, and is the rate limiting step in the metabolism ofboth these alcohols. The enzyme, alcohol dehydrogenase, has a greater affinity for ethanol than it does for methanol. Therefore, in the presence ofethanol, the metabolism ofmethanol to its toxic metabolites is greatly slowed. Ifthere is a high clinical suspicionthat a patient has ingested methanol it is appropriate to begin an ethanol drip while awaitingblood levelsofmethanol. Ethanol drips are also indicated ifthe blood methanollevel returns and is 20 mg/dl or above. The target ethanol level is 100-150 mg/dl since this is the level that will saturate alcohol dehydrogenase. The recommendations for loading doses and maintenance drips are seen on table 2 below. This table assumes a typical volume ofdistribution and elimination. Clearly, ethanol levels must be frequently checked to assure an adequate ethanol level. Chronic drinkers need a higher rate ofethanol administration. The intravenous route ofadministration needs to be done through a central line because 10% ethanol has high osmolality.

Table 2: Standard ethanol dosing in a typical adult:

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Nondrinker Drinker Loading dose: * Abcohjfe amountofethanol: 600mgfeg eOOmgAg * Volume of 10% I.V. solution 7.6m»kB 7.8mt*g

Maintenance dose: * Amount ofabeohita ethanol QQmg^g/hr 154mgAg/hr * Volume of 10% I.V. *oJutbn 0.83 mVkgfht 1.9SmHg/hr

Maintenance dose during dtaiyaia: * Amount ofabsolute ethanol 169mg/kg/hr 257mg/kg/nr * Volume of 10% patentstaleolutbn 2.13 ml*g/hr 326mH

(one ml ofabsolute ethanol contains 790 mg ofethanol (specific gravity 0.79) so a 10% ethanol solution has 79g/dl and an 86-proofalcoholic beverage has 34 grams per dl)

** Forced diuresis has little effect on methanol elimination, however, dialysis is very effective in the removal ofboth methanol and formic acid from the body. Hemodialysisis preferred over peritoneal dialysis because it offers a more rapid mechanism ofclearance. Hemoperfusion should not be used because the columns may quickly become saturated with the methanol and then become ineffective. Hemodialysis also has the advantage ofbeing able to correct the metabolic acidosis or fluid and electrolyte disturbances that may be present. Indicationsfor dialysis include ocular manifestations of toxicity, all cases in whichthe patient may have underlying renal impairment, and a peak methanol level greater than 50 mg/dl. It is important to remember that levels below 50 mg/dl may still have significant toxicitybecause the majorityofthe measured methanol has alreadybeen converted into its toxic metabolites. Thus, the most important consideration in dialysis in the presence ofclinical manifestations and a severe metabolicacidosis. Ifdialysis is initiated the ethanol drip must be increased. Dialysisshould be continueduntil the methanol levelfalls below 20 mg/dl. The patient must be followed closely after dialysis as a 'rebound' phenomenonhas been well documentedwith the methanol levels increasingas much as 20 mg/dl over the 72 hour period following dialysis.

** Additional therapeutic intervention for methanol poisoning includes controllingthe degree of metabolic acidosis. This is accomplished by administering sodiumbicarbonateto the patient. This should be considered in acidotic patients with a bicarb, lessthan 15 mEq/L. The patient's sodium, pH, and potassium must be monitored. Some reports suggestthat such therapy may amelioratethe ocular manifestations and possiblyreduce the mortality.

** A final consideration in the treatment ofmethanol intoxication is the addition offolate acid to the patients treatment regimen. The enzymesthat metabolizeformic acid into C02 in humans are folic acid dependent. Clearly, folic acid deficiency could decrease the rate ofmetabolism offormic acid. Whether folic acidis beneficial in a person who does not havefolic acid deficiency is not clear but it is probably prudent to administer this agent.

On the Horizon: Pyrazole is known to be a potent competitive inhibitor ofalcohol dehydrogenase. 4-Methyl pyrazole is an even more specific inhibitorofthis enzymeand has less side effects than the former agent. Thiscompound hasbeenshown to inhibit the production offormic acidfrom methanol in experimental models. This agenthasalsobeenshown to be beneficial in ethylene glycol intoxication. Unfortunately, this medicationis still not approved for use in the U.S.

Pediatric Considerations: Children tolerate the severe metabolic acidosis less well than do adults and it must be carefully managed. Ethanolis still the antidote of choice and levels ofgreater than 100mg/dl are

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desired. This is accomplished with anTVinfusion of600 mg/kg bolus followed by 110 mg/kg/hr. The ethanol must be administered in a large volume offluid which canbecome a problemin children. At times the ethanolmust be given orallyto prevent fluid overload in the pediatric population. As with adults, blood levels ofgreater than 50 mg/dl ofmethanol require hemodialysis.

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