Toxicity Assessment Division, National Health and Environmental Effects Research Laboratory, Office of Research and Development, U.S. Environmental Protection Agency, Research Triangle Park, NC 27711, USA.
Neurotoxicol Teratol. 2012 Jan-Feb;34(1):83-9. doi: 10.1016/j.ntt.2011.11.001. Epub 2011 Nov 21.
Reports of behavioral effects of repeated inhalation of toluene in rats have yielded inconsistent findings. A recent study from this laboratory (Beasley et al., 2010) observed that after 13 weeks of inhaled toluene ("subchronic" exposure scenario), rats showed mild but persistent changes in behavior, primarily involving acquisition of an autoshaped lever-press response. The present experiment sought to systematically replicate these findings, using a 4-week "sub-acute" exposure scenario. Adult male Long-Evans rats inhaled toluene vapor (0, 10, 100, or 1000 ppm) for 6h/day, 5 days/week for 4 weeks. As in the subchronic study, toluene had no effect on motor activity, anxiety-related behavior in the elevated plus-maze, or acquisition of the visual discrimination. However, sub-acute toluene did not affect appetitively-motivated acquisition of the lever-press response, but did reduce accuracy of signal detection at the end of training. Analysis of the deficit in accuracy in the 1000 ppm group by means of manipulations of different task parameters suggested a greater influence of attentional impairment than visual or motor dysfunction as a source for the deficit. These results confirm a pattern of subtle and inconsistent long-term effects of repeated daily exposure to concentrations of toluene vapor of 1000 ppm and below, in contrast to robust and reliable effects of acute inhalation of the solvent at concentrations above 1000 ppm.
关于大鼠反复吸入甲苯的行为影响的报告得出了不一致的结果。本实验室最近的一项研究(Beasley 等人,2010)观察到,在吸入甲苯 13 周(“亚慢性”暴露情景)后,大鼠表现出轻微但持续的行为变化,主要涉及自动形成杠杆按压反应的获得。本实验旨在使用 4 周的“亚急性”暴露情景系统地复制这些发现。成年雄性 Long-Evans 大鼠每天吸入甲苯蒸气(0、10、100 或 1000 ppm)6 小时,每周 5 天,持续 4 周。与亚慢性研究一样,甲苯对运动活动、高架十字迷宫中的焦虑相关行为或视觉辨别力的获得没有影响。然而,亚急性甲苯蒸气并未影响奖赏性动机获得杠杆按压反应,但确实降低了训练结束时信号检测的准确性。通过操纵不同的任务参数对 1000 ppm 组准确性缺陷的分析表明,注意力损害的影响大于视觉或运动功能障碍,是造成缺陷的原因。这些结果证实了反复每日暴露于 1000 ppm 及以下浓度的甲苯蒸气会产生微妙而不一致的长期影响,而急性吸入高于 1000 ppm 的溶剂则会产生强大而可靠的影响。