Page x, lines 2–13. The NAC should consider using the following three paragraphs, rather than the first two existing paragraphs, as an introduction to the Executive Summary:
Methanol (also known as wood alcohol) is a clear, colorless, volatile, flammable liquid with a sweet odor. It is used in paint removers, windshield washer fluid, automotive fuel, and antifreeze; as an industrial solvent; and as a raw material in the production of many commercially important organic compounds. Small amounts of methanol are produced over the course of normal body metabolism and are found in the exhaled air.
Methanol is rapidly absorbed after ingestion or inhalation. Percutaneous absorption is also considerable. Acute methanol toxicity varies greatly between species, primarily as a result of differential metabolism. At very high inhaled concentrations rodents exhibit much higher blood methanol concentrations than do primates. Primates accumulate greater amounts of the important toxic metabolite—formic acid (found in equilibrium in plasma with its anion, formate). Primates are more susceptible than rodents because of the greater accumulation of formates in primates. Clinical experience with those who ingested methanol (often under the mistaken assumption that they were consuming ethanol) demonstrates marked variations in individual susceptibility and delayed onset of severe, overt toxicity. The initial phase of inebriation is similar to that seen after ethanol but is usually mild and transient and is generally followed by an uneventful initial recovery. The most important clinical consequences develop between 6 and 30 hours after the initial exposure.
Wide individual variations in response are most likely due to individual rates of formate production from methanol in the liver. People with pre-existing liver disease (e.g., cirrhosis) often appear resistant to methanol poisoning because of their relatively inefficient conversion of methanol to formic acid. Accumulation of formate in primates leads to depletion of the normal bicarbonate buffering capacity of the body, delayed-onset metabolic acidosis and death with acute cerebral edema, CNS depression, and coma. The severity of the poisoning and the patient’s prognosis are related directly to the extent of formate and lactate formation, which account largely for this metabolic acidosis. Among victims who survive the initial phase, vision can become severely impaired and permanent bilateral blindness can follow formate-induced retinal edema, demyelination of the temporal retina, hemorrhagic necrosis in the basal ganglia, and nerve head pallor. Pancreatitis has been associated with acute abdominal pain. Occupational methanol exposures in confined spaces or in workrooms with inadequate ventilation have been associated with recurrent giddiness (mild inebration), nausea, insomnia, blurred or dim vision, and conjunctivitis. The delayed onset of symptoms, the potent ocular degeneration, and the metabolic acidosis seen in primates poisoned with methanol are not observed in rodents. AEGL derivations should not be based on rodent data because of these pronounced interspecies differences in metabolism and toxicity.
Page x, lines 17–18. Undue attention is paid to the occupational exposure limit of 200 ppm, a level identified as an 8-hour time-weighted average (TWA) that was also selected as the TLV, REL, and PEL. The value was based on a recommendation by Warren Cook (Ind. Med. 14:936–946, 1945) that he made after reviewing a study (Sayers, R.R., et al. U.S. Bureau of Mines Report of Investigations No. 3617, USBM, Washington, DC, 1942) that found no adverse effects in dogs exposed 7 days weekly for 379 days to methanol vapor at 450–500 ppm. Thus, there is nothing unique about 200 ppm value except that it has been accepted and