CARBONYL SULFIDE CLEAN AIR ACT STUDIES

工作总结：人们对吸入羰基硫化物的致癌潜力感到担忧，因为它具有化学活性，预计会与呼吸道组织发生反应。此外，羰基硫化物是二硫化碳的氧化产物，已被证明在菌株A小鼠肺癌生物试验中呈阳性。在A/J小鼠中观察到发病率(荷瘤小鼠)和频率(肺腺瘤的小鼠肿瘤数)显著增加。NTP发现，在Ames试验中，羰基硫化物产生了微弱的阳性反应(这些是唯一的遗传毒性数据)。遗传毒性和癌症研究问题将在小鼠和TG.AC小鼠的P53敲击中进行评估，随后将在大鼠和小鼠中进行慢性测试。对于非癌症的毒性，羰基硫化物有神经毒性方面的担忧。一项对大鼠吸入4小时的急性毒性研究显示，1062和1189 ppm对中枢神经系统有一些影响。一项在兔身上进行的持续7周的54ppm吸入研究也报告了神经障碍。然而，这些研究还不足以充分描述羰基硫化物的神经学风险，因为它们的目的不是对急性和亚慢性暴露后神经毒性的适当参数进行全面评估。这项研究的方法是在内部进行一项综合的吸入毒性研究，包括毒代动力学、神经、行为、电生理和病理终点，检查剂量反应关系和潜在的毒性机制。然后，这些研究的信息将被用于规划更长的剂量反应关系和潜在的毒性机制。然后，这些研究的信息将被用于计划更长期的研究。第三个问题是，需要进行两代研究，以评估在发育过程中暴露的第二代对哺乳和生殖性能的影响。将使用短期生殖和发育毒性筛查来提供数据，以确定接触COS后是否会产生生殖和发育影响。

Summary of Work: There is concern for the carcinogenic potential of carbonyl sulfide by inhalation because it is chemically reactive and is expected to react with tissues of the respiratory tract. Furthermore, carbonyl sulfide is the oxidation product of carbon disulfide which has been shown to be positive in the strain A mouse lung tumor bioassay. Significant increases in the incidence (tumor-bearing mouse) and frequency (tumors per mouse of lung adenomas) was observed in A/J mice. NTP found that carbonyl sulfide produced a weak positive response in the Ames assay (these are the only genetic toxicity data). Genotoxicity and cancer research issues will be evaluated in the p53 knock of mouse and TG.AC mouse, followed by chronic testing in rats and mice. For noncancer toxicities, there is a neurotoxic concern for carbonyl sulfide. An acute toxicity study in rats via inhalation for 4 hours showed some central nervous system effects at 1,062 and 1,189 ppm. An inhalation study in rabbits at 54 ppm for 7 weeks also reported neurological disorders. However, these studies are not sufficient to adequately characterize the neurological risk of carbonyl sulfide because they were not intended to provide a full evaluation of appropriate parameters for neurotoxicity following both acute and subchronic exposures. The approach to the study is to conduct an integrated inhalation toxicity study in-house including toxicokinetic, neurological, behavioral, electrophysiological and pathological end points examining dose response relationships and potential mechanisms of toxicity. Information from these studies will then be used to plan longer dose response relationships and potential mechanisms of toxicity. Information from these studies will then be used to plan longer term studies. A third concern is that a two generation study is needed to assess the effects on lactation and the reproductive performance of the second generation that was exposed during development. A short term reproductive and developmental toxicity screen will be used to provide data as to whether reproductive and developmental effects occur following COS exposure.