TheJoufnalofEmergencyMedicine, Vol. 1, pp. 51-58,1983 Printed in the USA*Copyright 0 1983 Pergamon Press Ltd METHANOL POISONING Charles E. Becker, MD Northern California Occupational Health Center, San Francisco General Hospital and Medical Center; and the Department of Medicine, University of California-San Francisco Reprint address: San Francisco General Hospital, Building 30, 5th Floor, 1001 Potrero Avenue, San Francisco, CA 94110 ??Abstract -Methanol poisoning is an uncom- significantly higher in cases of severe methanol mon but an extremely hazardous intoxication. poisoning than in mild cases. Once the diagno- Since methanol is a versatile fuel and is having sis is suspected, a blood level from methanol increasing usage in an energy-conscious society, should be returned rapidly. Treatment of meth- a high index of suspicion and swift laboratory anol toxicity after good supportive care is to di- confirmation is essential in managing this poi- minish the metabolic degradation of methanol soning. Methanol poisoning may occur in spor- with simultaneous ethanol and then to perform adic or epidemic circumstances. Chronic expos- hemodialysis and alkalinization to counteract ure may occur in the occupational setting. Man metabolic acidosis. Folate should also be ad- is uniquely susceptible to methanol toxicity, ministered to enhance metabolic breakdown of perhaps dependent upon folate metabolism. formate. Alcoholic patients may be especially Classic symptoms of methanol toxicity can only susceptible to methanol poisoning due to rela- occur in laboratory animals who are rendered tive folate deficiency. folate deficient. Folate may be useful in humans enhancing removal of the toxic products of 0 Keywords-methanol; formate; 4-methyl methanol poisoning. The enzyme responsible pyrazole; anion and osmolar gaps for metabolism of methanol is alcohol dehydro- genase. Ethanol has a higher affinity for this en- zyme and is preferentially metabolized. Simul- Methanol (methyl alcohol) can be derived taneous ethanol and methanol administration from a large number of unused and dis- may confuse the onset of the intoxication. Pyra- carded potential energy sources, and has zoles may also be used to inhibit alcohol dehy- excellent combustion mixing properties. drogenase thus preventing the intoxication. The For this reason it has been proposed as a most important initial symptom of methanol gasoline additive, as a home heating mate- poisoning is visual disturbance. The symptoms rial, and as feedstock in bacterial synthesis may be delayed up to 24 hours after ingestion for protein. The home application of meth- due to simultaneous alcohol administration and metabolic processes. Laboratory evidence of se- anol includes the use of “canned heat,” such vere metabolic acidosis with increased anion as Sterno@, and the use of windshield wash- and osmolar gaps strongly suggest the clinical ing materials. In addition, it is a common diagnosis. There may be an important associa- component of paints, varnishes, solvents, tion between mean corpuscular volume which is antifreeze solutions, and is utilized both in Selected Topics- devoted to a broad range of articles from prehospital care and new ====== technologies to toxicologic emergencies and disaster management -is coordinated by Kenneth Kulig, MD, of the Rocky Mountain Poison Center. RECEIVED: I8 November 1982; ACCEPTED: 19 January 1983 0736-4679/83$3.00 f .OO 51 Charles E. Becker denaturing ethanol and as an alternative Swartz and his colleagues4 reported an fuel source. epidemic in the State Prison of Southern Methanol is generally obtained from the Michigan in May 1979. In this instance sev- destructive distillation of wood; the greater eral inmates obtained a quantity of diluent, the extent of distillation the more palatable ordinarily used in photocopying machines, the odor of the methanol. Methanol may which was nearly pure methanol. The in- contain impurities which impart to it a dis- mates distributed this fluid in smail quanti- agreeable odor and taste. Without impuri- ties as “homemade” spirits. Forty-six defi- ties methanol more easily contributes to nite cases of intoxication were identified; dangerous accidental and deliberate poison- they were either treated initially in the pris- ings which can reach epidemic proportions. on infirmary, or referred to a local hospital The toxicology of methanol was not un- center for further evaluation and treat- derstood for many years. Wines, brandies, ment. Three deaths occurred; one speci- and whiskeys containing a substantial per- men of the beverage retrieved from an in- centage of methanol were sold in the late mate revealed a pink fruity liquid which 1800s. Results of early experiments with was 4% methanol by weight. animals were inconsistent in describing Children have also become intoxicated methanol’s toxicity. It was not until the by methanol. A lo-week-old infant was late 1920s when a group of workers in Ger- admitted to a hospital with a methanol level many were poisoned with chemically pure of 213 mg/dL nine hours after methanol methanol that the true toxicity of methanol was mistaken for distilled water and mixed was generally accepted. Bennett and his as- with formula.5 An 8-month-old child died sociates’ reported their observations on when methanol-soaked pads were placed 323 patients who ingested bootleg whiskey on the chest to treat a common cold.6 Fur- in Atlanta, Georgia during 5 days in Octo- ther emphasizing the dermal and respira- ber 195 1. Forty-one deaths occurred when tory absorption of methanol, the Polish 90 gallons of the methanol-contaminated literature reports a painter who accidental- whiskey were distributed throughout the ly spilled methanol on his clothes and shoes city. Later analysis of the confiscated ma- but continued to wear the soaked gar- terial showed it contained 35% to 40% ments; blindness developed within several methanol. As word of the poisoning spread days.7 by rumor, newspaper, and radio, a minor panic developed and numerous asympto- matic individuals presented themselves to Methanol Toxicology be evaluated. Kane and coworkers* report- ed an epidemic of poisoning in 18 individ- Pure methanol is a colorless liquid, has a uals (of whom 8 died) when a diluted paint specific gravity of 0.8 1, a boiling point of thinner was used as an alcoholic beverage 65”C, and a slight odor distinctly different in Lexington, Kentucky. The liquor was from that of ethanol. Methanol can be ab- served as a party refreshment. Naraqui sorbed through the skin, and through the and associates3 reported a severe outbreak respiratory and gastrointestinal tracts. The of methanol poisoning in Port Moresby, current threshold limit value for methanol New Guinea, in March 1977 when 28 men in industry is 200 ppm (260 mg/m3). Nor- attended a party and consumed the con- mal methanol blood concentrations derived tents of a drum of methanol that had been from endogenous production and dietary found in another village. Some of these in- sources are approximately 1.5 mg/L. There dividuals may have consumed as much as is great variability in the mean lethal dose 600 mL of pure methanol. Four died, six among animal species. had bilateral visual impairment, and two The special susceptibility of man to had persistent difficulty with speech. methanol toxicity is thought to be due not Methanol Poisoning 53 to methanol itself, but to its metabolite, ing the flow of the axoplasm and thus caus- formate. Review of clinical findings in epi- ing the pathological condition of the eye.13 demic situations and in isolated cases shows Current evidence does not suggest that for- great variation in the dose of methanol maldehyde causes these effects on the eye. required to produce acidosis, blindness, Due to their high rate of metabolism of and death. Some of this clinical confusion formate, rats do not accumulate it; hence, may be explained by individual metabolic rats do not manifest methanol toxicity. A differences, associated ethanol consump- folate-dependent system is likely to be re- tion, or availability of essential cofactors sponsible for the oxidation of formic acid needed for methanol or formate metabo- to carbon dioxide in the liver of rats, mon- lism. The smallest amount of methanol re- keys, and probably in humans. The level of ported to cause death is 15 mL of 40% folate appears to be critical for formate methanol; the highest dose recorded for a metabolism in animals. The classic symp- survivor is in the range of 500 to 600 mL.3 toms of methanol toxicity in rats can only Most cases of severe human poisoning oc- be produced by rendering these animals fo- cur by the oral route. Occasional cases oc- late deficient.14 Experiments in monkeys cur by skin contact and inhalation. strongly suggest that folate decreases for- Methanol is rapidly absorbed from the mate accumulation after methanol over- gastrointestinal iract, with peak absorp- dose by stimulating formate oxidation; tion occurring in 30 to 60 min depending this suggests that folate may be useful in on the presence or absence of food in the reducing the toxicity of methanol.r4 stomach. Methanol distributes in total The enzyme primarily responsible for body water, although its passage through methanol oxidation in the liver is alcohol cellular membranes may be different from dehydrogenase (ADH). Ethanol has a that of water. The primary method of higher enzyme affinity for ADH and is elimination of methanol in humans is by its preferentially metabolized; as a result, oxidation to formaldehyde, formic acid, methanol is eliminated primarily by extra- and carbon dioxide. Methanol may also hepatic routes when ethanol is present. exit the body with induced vomiting, and a Ethanol concentrations in the range of 100 small amount is excreted in the breath, to 200 mg/dL are clinically regarded as be- sweat and urine. Increasing urine flow ing optimal for saturating alcohol dehy- would be expected to increase methanol drogenase to prevent methanol metabo- excretion to some extent, but forced diure- lism.