Reaction mass of methyl acetate and methanol

Endpoint summary

Description of key information

The reaction mass of methyl acetate and methanol is assessed on the basis of the individual constituents methyl acetate and methanol using a read-across approach from the supporting substances (structural analogue or surrogate).

 

Based on the toxicity results of the two source substances methyl acetate and methanol, the toxicity of the reaction mass of methyl acetate and methanol is assessed. Following a worst scenario, methanol, the more critical of both substances, is used for assessment. Based on extensive experience in humans, assessment, especially for acute toxic effects, is only based upon the experiences in humans and classifies methanol as acutely toxic by oral, dermal and inhalative exposure and, furthermore, as capable of inducing serious irreversible effects upon single exposure by all of these routes.

Additional information

Acute toxicity, human data for methanol

Due to misuse of methanol in the production of alcoholic beverages oral ingestion is the most frequent route of poisoning, death and blindness from methanol. However, there are also case reports from percutaneous absorption or vapor inhalation having elicited the methanol acute toxic syndrome.

 

Exposure-related observations in humans + direct observations: Clinical cases, poisoning incidents, RL2

A blood level of 500 mg/L methanol in acutely poisoned patients is generally regarded as an indication for hemodialysis. This blood concentration can transiently be achieved in an adult person (70 kg) by ingestion of 0.4 mL methanol/kg bw (Kavet and Nauss, 1990). Generally in humans, transient central nervous system (CNS) effects appear at blood methanol levels of 200 mg/L and serious ocular symptoms appear above 500 mg/L ranging from mild photophobia, misty or blurred vison to markedly reduced visual acuity and total blindness (Kavet and Nauss, 1990; Dethlefs and Naraqi, 1978).

 

Exposure-related observations in humans, RL2

Acute methanol intoxication evolves in a well-defined pattern. First, a mild depression of the CNS occurs which is followed by an asymptomatic latent period commonly lasting 12 to 14 hours. Clinical symptoms include headache, dizziness, nausea and vomiting, abdominal pain, and labored, periodic breathing and mag progress to coma and death from respiratory failure (Kavet and Nauss, 1990).

 

Exposure-related observations in humans, RL2

The minimal acute methanol dose to humans that can result in death is considered to be 300 to 1000 mg/kg by ingestion. Fatalities have occurred in untreated patients with initial methanol blood levels in the range of 1500 to 2000 mg/L (IPCS/WHO, 1997).

 

Direct observations: Clinical cases, poisoning incidents, RL2

In general, coma, seizures and prolonged acidosis were poor prognostic signs (Naraqi et al., 1979).

 

Exposure-related observations in humans, RL2

Such high and potentially lethal blood methanol levels are less likely to be achieved from inhalation exposure. Exposure to 0.26 mg/L methanol for 4 hours was without significant physiologic effects in human volunteers (Muttray et al., 2001).

 

Conclusion

In conclusion, there are two dominating acute effects from methanol: blindness and metabolic acidosis. For the latter, formate is considered to be the ultimate toxicant in acute methanol intoxication in humans. Acidosis and ophthalmologic changes are typical effects in primates. They do not occur in rodents or rabbits, which are able to remove formate more efficiently. In these animals, CNS depression, narcosis and death are the leading symptoms of intoxication.Although the mechanism for optic nerve damage from exposure to methanol has not been established, a potential role of formate is expected.