Biomedical Engineering Reference
In-Depth Information
Contrary to observations by Gilger and Potts (1955), there was no
evidence of marked acidosis in 12 rhesus monkeys after methanol doses
up to 6000mg/kg bw (20-30% methanol in water). There was no
hyperventilation, no increase in urinary excretion of organic acids,
or shift in serum bicarbonate or death. Blindness was seen in only one
surviving monkey dosed with 9000mg/kg bw. The effect was judged to
be transient 4 days after exposure (Cooper and Felig, 1961).
The metabolism of methanol in monkeys is more like the metabolism
in humans and the toxic response seen in monkeys is more like humans
than seen in other animal species. At higher oral doses of methanol, the
monkeys showed severe intoxication, extended edema in the retina and
in the optic papilla, and the pupils were wide and nonresponsive.
Six of eight rhesus monkeys dosed with 6000-mg/kg bw methanol
followed by sodiumbicarbonate to counteract the acidosis, exhibited cystic
degeneration of the outer retinal granular layer, and in one animal therewas
evidence of significant demyelinisation of the optic nerve. One out of eight
monkeys survived for 9 days. Histological lesions were seen in the putamen
and nucleus caudatus in three of eight monkeys (Potts et al., 1955).
Four out of the eight rhesus monkeys died following oral dosing of
6 gm/kg and treatment with sodium bicarbonate to counteract the
acidosis. This was one of the first studies to show improved survival
at lethal does as a result of treatment to counteract the acidosis. Most
animals showed retinal edema (confined to perimascular regions in
some and extending to the entire fundus in others) (Potts, 1955).
Gilger and Potts (1955) concluded that when compared to the mean
lethal oral dose of methanol in humans, the rats had a mean lethal dose
that was nine times higher, while the mean lethal dose in the rabbit was
seven times higher, in the dog nine times higher, and in the monkey
three times higher than the mean lethal dose of methanol in humans.
4.2.2 Dermal
Table 4.2 presents mortality from single dermal treatment of methanol
in various animal species.
According to an early report, all rats survived 35,000mg/kg bw after
occlusive skin application of methanol, while deaths were reported at
