Methanol Poisoning: Role of Formate Metabolism in the Monkey

McMartin, Kenneth E.; Martin-Amat, G.; Makar, A B; Tephly, Thomas R.

doi:10.1016/b978-0-12-691402-3.50045-7

Cited by 58 publications

(48 citation statements)

References 9 publications

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“…1) is not of major importance and that the primary pathway to CO2 from formate occurs via the tetrahydrofolic acid pathway. This has been demonstrated in rat liver perfusates (23), monkeys (14) and rats (24). Since the tetrahydrofolic acid pathway (Fig.…”

Section: Metabolismmentioning

confidence: 99%

“…Thus, the rat is able to convert formate to CO2 at more than twice the rate of monkeys (or man) and, as a result, has lower blood formate levels (14) and does not excrete formate in the urine (20). Man additionally possesses 50% more hepatic dehydrogenase than do rats (30).…”

Section: Metabolismmentioning

confidence: 99%

“…In a somewhat different experiment, McMartin et al. (14) administered '4C-methanol by gastric intubation. Again, formaldehyde could not be detected although formate levels increased rapidly.…”

Section: Metabolismmentioning

confidence: 99%

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Report of the Federal Panel on Formaldehyde

1982

Environmental Health Perspectives

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The Federal Panel on Formaldehyde concluded that definitive experiments exist which demonstrate the mutagenicity and carcinogenicity of formaldehyde under laboratory conditions. Formaldehyde induces both gene mutations and chromosomal aberrations in a variety of test systems. Inhalation of formaldehyde causes cancer of the nose in rats. The concentrations of formaldehyde in inhaled air that caused nasal cancer in Fisher 344 rats are within the same order of magnitude as those to which humans may be exposed. The data presently available do not permit a direct assessment of the carcinogenicity of formaldehyde to man. Epidemiologic studies on exposed human populations are in progress and may further clarify the situation. Other experimental and human studies on toxic effects such as teratogenicity and reproductive disorders are as yet inadequate for a health risk assessment.The CIIT 24 month study on animal carcinogenicity has not yet been completely evaluated. Additional data are expected on the effects of prolonged exposure to lower doses of formaldehyde and on the possible carcinogenicity of formaldehyde in the mouse. The panel recommends that, for a comprehensive health risk assessment, further experiments be conducted on the effects of other modes of exposure (ingestion and skin penetration), the effects in humans, and on the pharmacokinetics of formaldehyde in man and animals and the possible role for formaldehyde in reproductive and chronic respiratory disorders.It is the conclusion of the panel that formaldehyde should be presumed to pose a carcinogenic risk to humans.

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Section: Metabolismmentioning

confidence: 99%

Section: Metabolismmentioning

confidence: 99%

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Report of the Federal Panel on Formaldehyde

1982

Environmental Health Perspectives

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“…Methanol is first metabolized to formaldehyde, which is very rapidly metabolized into formic acid, so that very little formaldehyde is detected in tissues . Formic acid is then metabolized to CO 2 (McMartin et al, 1977). The conversion rate of formic acid to CO 2 in primates is less lhan half of that in nonprimates (McMartin et al, 1977).…”

Section: Pharmacokinetics and Metabolismmentioning

confidence: 99%

Spacecraft Maximum Allowable Concentrations for Selected Airborne Contaminants, Volume 1

Nasa¹

1994

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“…As one would parts. 106 In all of these cases, the effect of dietary folate on formate metabolism was the direct link to altered sensitivity to methanol; slowing formate metabolism induced a methanol-sensitive state.…”

mentioning

confidence: 99%

The Toxicity of Inhaled Methanol Vapors

Kavet¹,

Nauss²

1990

Critical Reviews in Toxicology

158

102

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Methanol could become a major automotive fuel in the U.S., and its use may result in increased exposure of the public to methanol vapor. Nearly all of the available information on methanol toxicity in humans relates to the consequences of acute, rather than chronic, exposu res. Acute methanol toxicity evolves in a well-understood pattern and consists of an uncompensated metabolic acidosis with superimposed toxicity to the visual system. The toxic properties of methanol are rooted in the factors that govern both the conversion of methanol to formic acid and the subsequent metabolism of formate to carbon dioxide in the folate pathway. In short, the toxic syndrome sets in if formate generation continues at a rate that exceeds its rate of metabolism. Current evidence indicates that formate accumulation will not challenge the metabolic capacity of the folate pathway at the anticipated levels of exposu re to automotive methanol vapor.

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Methanol Poisoning: Role of Formate Metabolism in the Monkey

Cited by 58 publications

References 9 publications

Report of the Federal Panel on Formaldehyde

Report of the Federal Panel on Formaldehyde

Spacecraft Maximum Allowable Concentrations for Selected Airborne Contaminants, Volume 1

The Toxicity of Inhaled Methanol Vapors

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