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Toxicological information

Epidemiological data

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Administrative data

Endpoint:
epidemiological data
Type of information:
experimental study
Adequacy of study:
weight of evidence
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Data from collection of data (review)

Data source

Reference
Reference Type:
publication
Title:
Methanol, Environmental Health Criteria 196
Author:
IPCS/WHO
Year:
1997
Bibliographic source:
International Programme on Chemical Safety, World Health Organisation Geneva, 1997

Materials and methods

Endpoint addressed:
basic toxicokinetics
acute toxicity: oral
repeated dose toxicity: inhalation
Principles of method if other than guideline:
Information on methanol toxicity in humans (symptoms and signs of methanol poisoning).

Test material

Constituent 1
Reference substance name:
Methanol
EC Number:
200-659-6
EC Name:
Methanol
Cas Number:
67-56-1
Molecular formula:
CH4O
IUPAC Name:
methanol

Method

Details on study design:
Humans (and non-human primates) are uniquely sensitive to methanol poisoning and the toxic effects in these species is 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 vapour and percutaneous absorption of methanolic liquids are as effective as the oral route in producing acute toxic effects. The most noted health consequence of longer-term exposure to lower levels of methanol is a broad range of ocular effects.
The toxic properties of methanol are based on factors that govern both the conversion of methanol to formic acid and the subsequent metabolism of formate to carbon dioxide in the folate pathway. The toxicity is manifest if formate generation continues at a rate that exceeds its rate of metabolism.

The severity of the metabolic acidosis is variable and may not correlate well with the amount of methanol ingested. The 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 detoxicification.

Results and discussion

Results:
The lethal dose of methanol for humans is not known for certain. 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.
The symptoms and signs of methanol poisoning, which may not appear until after an asymptomatic period of about 12 to 24 hours, include visual disturbances, nausea, abdominal and muscle pain, dizziness, weakness and disturbances of consciousness ranging from coma to clonic seizures. Visual disturbances generally develop between 12 and 48 h after methanol ingestion and 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 anion-gap type. The acidosis is largely attributed to the formic acid produced when methanol is metabolized. The normal blood concentration of methanol from endogenous sources is less than 0.5 mg/litre (0.02 mmol/litre), but dietary sources may increase blood methanol levels. Generally, CNS effects appear above blood methanol levels of 200 mg/L (6 mmol/L), and fatalities have occurred in untreated patients with initial methanol levels in the range of 1500-2000 mg/L (47-62 mmol/L). Visual disturbances of several types (blurring, constriction of the visible field, changes in colour perception, and temporary or permanent blindness) have been reported in workers who experienced methanol air levels of about 1.6 mg/L (corresponding to 1200 ppm) or more. A widely used occupational exposure limit for methanol is 0.26 mg/L (corresponding to 200 ppm), which is designed to protect workers from any of the effects of methanol-induced formic acid metabolic acidosis and ocular and nervous system toxicity.
No other adverse effects of methanol have been reported in humans except minor skin and eye irritation at exposures well above 0.27 mg/L (corresponding to 200 ppm).

Applicant's summary and conclusion