© 1993 Oxford University Press
research-article |
Acute Methanol Toxicity in Minipigs1
*Chemical Industry Institute of Toxicology U.S. Environmental Protection Agency, Research Triangle Park North Carolina 27709
Health Effects Research Laboratory, U.S. Environmental Protection Agency, Research Triangle Park North Carolina 27709
College of Veterinary Medicine, North Carolina State University Raleigh, North Carolina 27607
Received August 27, 1992; accepted December 21, 1992
The pig has been proposed as a potential animal model for methanol-induced neuro-ocular toxicosis in humans because of its low liver tetrahydrofolate levels and slower rate of formate metabolism compared to those of humans. To examine the validity of this animal model, 12 4-month-old female minipigs (minipig YU) were given a single oral dose of water or methanol at 1.0, 2.5, or 5.0 g/kg body wt by gavage (n = 3 pigs/dose). Dose-dependent signs of acute methanol intoxication, which included mild CNS depression, tremors, ataxia, and recumbency, developed within 0.5 to 2.0 hr, and resolved by 52 hr. Average maximum methanol concentrations in plasma, of 3100 ± 700 (SD), 6200 ± 2300, and 15,200 ± 900 µg/ml were reached within 0.5 to 4 hr following methanol administration in animals given 1.0, 2.5, or 5.0 g methanol/kg, respectively. The mean initial elimination half-lives of methanol were 9.0 ± 1.6, 22.4 ± 6.1, and 18.9 ± 4.3 hr, for 1, 2.5, and 5.0 g/kg doses, respectively. In 3 minipigs, a transient increase in plasma formate concentration (1.74–3.40 mEq/liter vs control = 0.5 + 0.3 mEq/liter) occurred 4 to 30 hr following methanol administration. Methanol- and formate-dosed pigs did not develop optic nerve lesions, toxicologically significant formate accumulation, or metabolic acidosis. Based on results following a single dose, female minipigs do not appear to be overtly sensitive to methanol and thus may not be a suitable animal model for acute methanol-induced neuroocular toxicosis.