Lee E W, Garner C D, Terzo T S
General Motors NAO Research and Development Center, Department of Automotive Safety and Health, Warren, Michigan 48090-9055.
Toxicol Appl Pharmacol. 1994 Oct;128(2):199-206. doi: 10.1006/taap.1994.1198.
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.
甲醇的中毒剂量可导致人类视觉功能障碍和代谢性酸中毒。然而，能够引发此类毒性的甲醇剂量范围以及视觉功能障碍的机制尚不清楚。即使给予致死剂量，非灵长类实验动物也不会出现典型的人类甲醇毒性。在本研究中，我们研究了在积累甲酸的叶酸缺乏（FR）大鼠模型中，甲醇是否能诱发视觉功能障碍。通过口服或吸入途径给大鼠施用甲醇。在接受甲醇刺激的FR大鼠（3.5 g/kg，口服）中，闪光诱发电位的P1和N1峰潜伏期显著增加，表明施用甲醇对视神经视网膜皮质视觉通路产生了不良影响。随后通过评估视网膜电图（ERG）来评估对视网膜功能的影响。口服甲醇（1.5至2.5 g/kg）后，ERG的b波振幅出现剂量相关的降低。在暴露于甲醇蒸气（2000 ppm，对猴子无毒的浓度）的FR大鼠中也出现了b波振幅降低。这些观察结果与报道的人类甲醇中毒病例一致。因此，我们的数据表明，FR大鼠模型可作为一种有价值的人类替代模型，用于研究甲醇诱导的视觉功能障碍机制，并在各种暴露情况下提供有关视觉系统的可靠毒性数据。
