Herr David W, Graff Jaimie E, Moser Virginia C, Crofton Kevin M, Little Peter B, Morgan Daniel L, Sills Robert C
Neurotoxicology Division, MD B105-05, NHEERL, ORD, USEPA, Research Triangle Park, North Carolina 27711, USA.
Toxicol Sci. 2007 Jan;95(1):118-35. doi: 10.1093/toxsci/kfl146. Epub 2006 Nov 1.
Carbonyl sulfide (COS), a chemical listed by the original Clean Air Act, was tested for neurotoxicity by a National Institute of Environmental Health Sciences/National Toxicology Program and U.S. Environmental Protection Agency collaborative investigation. Previous studies demonstrated that COS produced cortical and brainstem lesions and altered auditory neurophysiological responses to click stimuli. This paper reports the results of expanded neurophysiological examinations that were an integral part of the previously published experiments (Morgan et al., 2004, Toxicol. Appl. Pharmacol. 200, 131-145; Sills et al., 2004, Toxicol. Pathol. 32, 1-10). Fisher 334N rats were exposed to 0, 200, 300, or 400 ppm COS for 6 h/day, 5 days/week for 12 weeks, or to 0, 300, or 400 ppm COS for 2 weeks using whole-body inhalation chambers. After treatment, the animals were studied using neurophysiological tests to examine: peripheral nerve function, somatosensory-evoked potentials (SEPs) (tail/hindlimb and facial cortical regions), brainstem auditory-evoked responses (BAERs), and visual flash-evoked potentials (2-week study). Additionally, the animals exposed for 2 weeks were examined using a functional observational battery (FOB) and response modification audiometry (RMA). Peripheral nerve function was not altered for any exposure scenario. Likewise, amplitudes of SEPs recorded from the cerebellum were not altered by treatment with COS. In contrast, amplitudes and latencies of SEPs recorded from cortical areas were altered after 12-week exposure to 400 ppm COS. The SEP waveforms were changed to a greater extent after forelimb stimulation than tail stimulation in the 2-week study. The most consistent findings were decreased amplitudes of BAER peaks associated with brainstem regions after exposure to 400 ppm COS. Additional BAER peaks were affected after 12 weeks, compared to 2 weeks of treatment, indicating that additional regions of the brainstem were damaged with longer exposures. The changes in BAERs were observed in the absence of altered auditory responsiveness in FOB or RMA. This series of experiments demonstrates that COS produces changes in brainstem auditory and cortical somatosensory neurophysiological responses that correlate with previously described histopathological damage.
羰基硫（COS）是《原始清洁空气法》列出的一种化学物质，美国国立环境卫生科学研究所/国家毒理学计划与美国环境保护局联合开展了一项关于其神经毒性的研究。此前的研究表明，COS会导致皮质和脑干损伤，并改变对点击刺激的听觉神经生理反应。本文报告了扩展神经生理学检查的结果，这些检查是此前已发表实验的重要组成部分（Morgan等人，2004年，《毒理学与应用药理学》200卷，第131 - 145页；Sills等人，2004年，《毒理病理学》32卷，第1 - 10页）。将Fisher 334N大鼠置于全身吸入舱中，每天暴露于0、200、300或400 ppm的COS中6小时，每周5天，持续12周；或暴露于0、300或400 ppm的COS中2周。处理后，使用神经生理学测试对动物进行研究，以检查：外周神经功能、体感诱发电位（SEPs）（尾巴/后肢和面部皮质区域）、脑干听觉诱发电位（BAERs）以及视觉闪光诱发电位（2周研究）。此外，对暴露2周的动物使用功能观察组合测试（FOB）和反应修正听力测定法（RMA）进行检查。在任何暴露情况下，外周神经功能均未改变。同样，用COS处理后，从小脑记录的SEPs振幅也未改变。相比之下，在暴露于400 ppm COS 12周后，从皮质区域记录的SEPs振幅和潜伏期发生了改变。在2周的研究中，前肢刺激后SEP波形的变化程度大于尾巴刺激。最一致的发现是，暴露于400 ppm COS后，与脑干区域相关的BAER峰振幅降低。与2周的处理相比，12周后更多的BAER峰受到影响，这表明随着暴露时间延长，脑干的更多区域受到损伤。在FOB或RMA中听觉反应性未改变的情况下观察到了BAERs的变化。这一系列实验表明，COS会引起脑干听觉和皮质体感神经生理反应的变化，这些变化与先前描述的组织病理学损伤相关。
