Biomedical Engineering Reference
In-Depth Information
Rodents, rabbits, and dogs suffer from ataxia, narcosis, coma, and
death after high methanol doses. No acidosis or ophthalmologic
changes typically seen in humans at high doses were noted in animals
except in monkeys (Gilger and Potts, 1955).
The lethal oral dose of methanol in animals, especially rodents
is much higher than the lethal oral methanol dose in humans
(
1000mg/kg bw), highlighting the differences in metabolism
between various species (Roe, 1982). The LD
50
dose in rodents
ranges from 5085 to 14,400mg/kg bw. The lethal methanol dose in
monkeys is reported to be as low as 3000mg/kg (Kavet and Nauss,
1990), which is much closer to the lethal dose of
1000mg in
humans, while the lethal methanol dose in dogs is reported to be
between 4000 and 8000mg/kg bw and in rabbits the lethal methanol
dose is between 2000 and 14,000mg/kg.
On the basis of the acute oral data in rodents, methanol would be
classified (Hazard Category IV) as practically nontoxic or very low
toxicity by USEPA (2008).
In addition to acute oral studies on mortality, neurobehavioral effects
were evaluated in one study. Male Long-Evans rats were gavaged with
single methanol doses of 1000, 2000, and 3000mg/kg bw representing
about 10%, 20%, and 30% of the LD
50.
Ten minutes after dosing, the
animals were subjected to a fixed wheel running test to assess operant
running (FR20). The rats displayed no signs of overt intoxication such
as gait disturbance, but did exhibit a significant, dose-related reduction
in FR20 response at all dose levels suggesting that 1000mg/kg was a
Low Observed Adverse Effect Level (LOAEL) (Youssef et al., 1993).
Monkeys receiving methanol doses higher than 3000mg/kg by
gavage showed ataxia, weakness, and lethargy within a few hours of
exposure. These signs tended to disappear within 24 hours and were
followed by transient coma in some of the animals and death (Potts,
1955; Potts et al., 1955).
In a screening study, mortality was noted in monkeys given 3000,
4000, 6000, or 8000mg/kg bw of methanol orally, but not at a dose of
1000 or 2,000mg/kg bw methanol. Intoxication, acidosis, and ocular
effects were reported in the monkeys similar to what had been reported
in humans (Gilger and Potts, 1955).
