Carbonyl Sulfide Clean Air Act Studies

工作概述：由于羰基硫化物具有化学反应性，预计会与呼吸道组织发生反应，因此人们担心吸入羰基硫化物可能致癌。此外，羰基硫化物是二硫化碳的氧化产物，在A株小鼠肺肿瘤生物测定中显示为阳性。在A/J小鼠中观察到肺肿瘤发生率显著增加。国家毒理学规划发现，羰基硫化物在Ames试验中产生微弱的阳性反应（这是唯一的遗传毒性数据）。对于非癌症毒性，羰基硫化物有神经毒性。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定影响。对家兔进行的一项吸入研究也报告了神经系统疾病。然而，这些研究还不足以充分表征羰基硫化物的神经风险，因为它们并没有打算对急性和亚慢性暴露后的神经毒性提供适当参数的全面评估。该研究的方法是在内部进行综合吸入毒性研究，包括毒性动力学，神经学，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。从这些研究中获得的信息将用于规划长期研究和检查潜在的毒性机制。第三个问题是，需要进行两代研究，以评估在发育期间暴露的第二代对泌乳和生殖性能的影响。短期生殖和发育毒性筛查将用于提供数据，以确定接触COS后是否会对生殖和发育产生影响。

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 of lung tumors were 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). 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 term studies and examine potential mechanisms of toxicity. 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.