A rat model manifesting methanol-induced visual dysfunction suitable for both acute and long-term exposure studies.
A toxic dose of methanol can induce visual dysfunction and metabolic acidosis in humans. However, the methanol dose range capable of inducing such toxicities and the mechanism(s) of visual dysfunction are not clearly understood. Nonprimate laboratory animals do not develop the characteristic human methanol toxicities even after a lethal dose. In the present study, we investigated whether visual dysfunction can be induced by methanol in a folate-reduced (FR) rat model which accumulates formate. Methanol was administered to rats by either the oral or inhalation route. The latencies of P1 and N1 peaks of flash-evoked potentials were significantly increased in methanol-challenged FR rats (3.5 g/kg, po), indicating that methanol administration caused an adverse effect in the retinogeniculocortical visual pathway. Effects on retinal function were then assessed by evaluating the electroretinogram (ERG). A dose-related reduction in b-wave amplitude of the ERG was manifested following oral methanol administration (1.5 to 2.5 g/kg). The b-wave amplitude reduction was also manifested in FR rats exposed to methanol vapors (2000 ppm, a concentration which was nontoxic in monkeys). These observations were consistent with reported human methanol toxicity cases. Thus, our data suggest that the FR rat model could serve as a valuable human surrogate for studying mechanisms of methanol-induced visual dysfunction and providing reliable toxicity data on the visual system under various exposure scenarios.
Lee
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General Motors NAO Research and Development Center, Department of Automotive Safety and Health, Warren, Michigan 48090-9055.
Garner
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Terzo
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D000280:Administration, Inhalation; D000284:Administration, Oral; D000818:Animals; D002849:Chromatography, Gas; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004596:Electroretinography / Q000187:drug effects; D005074:Evoked Potentials, Visual / Q000187:drug effects*; D005494:Folic Acid Deficiency / Q000473:pathology; D005561:Formates / Q000097:blood; D008099:Liver / Q000378:metabolism; D008297:Male; D000432:Methanol / Q000008:administration & dosage / Q000097:blood / Q000633:toxicity*; D051381:Rats; D012160:Retina / Q000187:drug effects; D014786:Vision Disorders / Q000139:chemically induced* / Q000209:etiology
D005561:Formates; C030544:formic acid; D000432:Methanol