Pryor G T
SRI International, Menlo Park, CA 94025.
Neurotoxicol Teratol. 1991 Jul-Aug;13(4):387-400. doi: 10.1016/0892-0362(91)90087-d.
The purpose of these experiments was to determine the extent to which subchronic exposure of rats to toluene might cause symptoms similar to those seen in some heavy abusers of toluene-containing products. In the first exploratory experiment, weanling male Fischer-344 rats were exposed to air, toluene, n-hexane, or a mixture of toluene, n-hexane, and methyl ethyl ketone (8 h per day, 7 days per week) for 11 weeks. A mild peripheral neuropathy was revealed by measures of grip strength in the rats exposed to n-hexane alone or in the mixture, but not in the rats exposed to toluene. Instead, the rats exposed to toluene alone developed a persisting motor syndrome characterized by a shortened and widened gait and a widened landing foot splay. The rats exposed to toluene alone or in the mixture were also hearing impaired, but not the rats exposed to n-hexane alone. In the second experiment, done to confirm and extend these results, weanling male Fischer-344 rats were exposed to toluene under three different daily schedules--2,200 ppm continuously for 8 h per day; 4,400 ppm, 30 min each h, 8 h per day; or 6,200 ppm, 15 min each h, 8 h per day. The exposures were 7 days per week for 23 weeks. The motor syndrome and hearing impairment were replicated in all essential respects in all toluene-exposed groups with no appreciable differences attributable to the daily exposure schedules. The effects were still evident 15 weeks after the last exposure. Toluene inhibited weight gain in both experiments, and in the second experiment, it was found that skeletal growth (torso length, rump width) was also inhibited. Toluene did not significantly impair rotorod performance in either experiment or acquisition of a spatial-navigation task in the second experiment. No neuropathologic correlates of the persisting motor syndrome were found in either experiment when the rats were sacrificed 9 and 16 weeks after the last exposure, respectively. These results demonstrate that toluene can cause a persisting motor syndrome in rats that resembles, to some extent at least (i.e., wide-based ataxic gait), the syndrome seen in some heavy abusers of toluene-containing products.
这些实验的目的是确定大鼠亚慢性接触甲苯可能在多大程度上引发与某些大量滥用含甲苯产品者类似的症状。在首个探索性实验中，将断乳雄性Fischer-344大鼠暴露于空气、甲苯、正己烷或甲苯、正己烷与甲乙酮的混合物中（每天8小时，每周7天），持续11周。单独暴露于正己烷或混合物中的大鼠通过握力测量显示出轻度周围神经病变，而暴露于甲苯中的大鼠则未出现。相反，单独暴露于甲苯的大鼠出现了持续的运动综合征，其特征为步态缩短变宽以及着地时脚间距变宽。单独暴露于甲苯或混合物中的大鼠也存在听力受损情况，而单独暴露于正己烷的大鼠则未出现。在第二个实验中，为了证实并拓展这些结果，将断乳雄性Fischer-344大鼠按照三种不同的每日时间表暴露于甲苯中——每天连续8小时暴露于2200 ppm；每天8小时，每小时30分钟暴露于4400 ppm；或每天8小时，每小时15分钟暴露于6200 ppm。每周暴露7天，持续23周。在所有暴露于甲苯的组中，运动综合征和听力受损在所有关键方面均得到重现，且未发现每日暴露时间表导致的明显差异。在最后一次暴露15周后，这些影响依然明显。在两个实验中，甲苯均抑制了体重增加，并且在第二个实验中发现，骨骼生长（躯干长度、臀部宽度）也受到了抑制。在任一实验中，甲苯均未显著损害转棒性能，在第二个实验中也未影响空间导航任务的习得。在最后一次暴露分别9周和16周后处死大鼠时，在任一实验中均未发现与持续运动综合征相关的神经病理学关联。这些结果表明，甲苯可在大鼠中引发持续的运动综合征，该综合征至少在一定程度上（即宽基共济失调步态）类似于某些大量滥用含甲苯产品者所出现的综合征。
