Studies to Evaluate the Toxic Carcinogenic Potential of Test Agents

该合同的目标是为国家毒理学计划（NTP）的危害识别（或危害评估）活动提供支持，目标是预防因环境暴露于化学或物理剂而引起的疾病或不利影响。该合同包括各种测试材料和测试材料的类别，这些测试材料将通过吸入暴露途径进行测试，其中一些是蒸汽，而另一些是液体或固体气溶胶。该合同包括预慢性研究，以评估6种磨料爆破剂（ABA）的纤维化潜力和肺负荷，包括爆破砂、煤渣、石榴石、碎玻璃、钢砂和镜面赤铁矿。磨料爆破剂由于其硅含量和作为结晶二氧化硅的替代品而引起人类健康问题。除钢砂外，所有aba均完成了为期14天的研究并进行了报告。钢砂研究将不会进行，因为大块材料不能被磨碎以满足研究需要。用喷砂和镜面赤铁矿进行了39周的纤维原性研究，并进行了报道。此外，该合同还包括对9种金属加工液（Cimstar 3800、Trim SC210、Clearedge 6584、Cimtech 310、Syntilo 1023、Trim 229、Superedge 6768、Cimperial 1070和Trim VX）进行为期14天和90天的毒性研究。MWFs在职业环境中广泛使用，对使用它们的个人可能存在治疗风险。14天的研究被取消，Trim SC210、Trim VX、Cimstar 3800和Syntillo 1023直接进入已完成并报告的90天研究。Cimstar 3800的2年研究的活体部分已经结束，并在组织病理学中，而Trim VX的2年研究是活体研究。该合同还包括对三氧化二锑进行为期14天和2年的研究。三氧化二锑已被证明是某些啮齿动物的致癌物；然而，需要更好地控制接触和利用更多的种类，以最终确定三氧化二锑的致癌潜力，以便将结果用于人类风险评估。14天的研究已经完成并报告，2年的生活研究部分正在进行中。该合同还包括对50纳米和1微米尺寸的C60富勒烯纳米材料进行为期90天的研究，该研究已在2009财年完成并报告。该合同还包括测试三种人造黄油调味剂（ABAs、乙托因、2,3-戊二酮和2,3-丁二酮），为期14天（乙托因）、90天（乙托因、2,3-戊二酮和2,3-丁二酮）和2年（2,3-丁二酮）的研究。aba与职业暴露和包括闭塞性细支气管炎在内的人类健康影响有关。需要进行动物研究，以确定单个aba对人类健康的潜在影响。2,3-丁二酮和乙托因的90天研究已经完成并报告。为期2年的2,3-丁二酮研究已经开始。为期90天的2,3-戊二酮研究目前处于暴露产生和监测阶段。该合同还包括在90天的研究中测试邻苯二醛（OPA），该研究于2009财年完成。OPA正被用作已知的啮齿动物致癌物gluteraldehyde的替代品，因此需要动物毒性数据来确定OPA对人类的潜在治疗效果。该合同包括为期90天的对氯-a，a，a-三氟甲苯（PCTFT）研究。PCTFT广泛用于许多有机化学品的合成，人们担心其使用的增加会增加向大气中的释放。为期90天的研究已经完成并报告。

The goal of this contract is to provide support of National Toxicology Program (NTP) hazard identification (or hazard assessment) activities targeted toward the prevention of diseases or adverse effects caused by environmental exposure to chemical or physical agents. This contract includes a varied array of test materials and classes of test materials that are to be tested via the inhalation route of exposure, some are vapors while others are liquid or solid aerosols. This contract includes prechronic studies to evaluate the fibrotic potential and lung burden of 6 abrasive blasting agents (ABA) which includes blasting sand, coal slag, garnet, crushed glass, steel grit, and specular hematite. Abrasive blasting agents are of human health concern becasue of their content of Si and as replacements for crystalline silica. The 14-day studies have been completed and reported for all ABAs except steel grit. Steel grit studies will not be conducted because the bulk material cannot be milled to meet study needs. Thirty-nine week fibrogenicity studies with blasting sand and specular hematite have been conducted and reported. In addition this contract includes 14-day and 90-day toxicity studies for 9 metal working fluids (MWF) (Cimstar 3800, Trim SC210, Clearedge 6584, Cimtech 310, Syntilo 1023, Trim 229, Superedge 6768, Cimperial 1070, and Trim VX. MWFs are used extensively in occupational settings and present a possible heal risk to individuals using them. The 14-day studies were canceled and Trim SC210, Trim VX , Cimstar 3800, and Syntillo 1023 went directly to 90-day studies which have been completed and reported. The in-life portion of the Cimstar 3800 2-year studies is concluded and in histopathology while the 2-year studies of Trim VX are in-life. The contract also includes 14-day and 2-year studies of antimony trioxide. Antimony trioxide has been shown to be a carcinogen in some rodent species; however better controlled exposures and additional species need to be utilized to determine conclusively the carcinogenic potential of antimony trioxide so that the results can be used in human risk assessment. The 14-day studies have been completed and reported and the 2-year study in-life portion is ongoing. The contract also includes 90-day studies of C60 fullerene nanomaterials of 50nm and 1 micron sizes which have been completed and reported in FY-09. The contract also includes testing three artificial butter flavoring agents (ABAs, acetoin, 2,3-pentanedione, and 2,3-butanedione) in 14- day (acetoin), 90-day studies (acetoin, 2,3-pentanedione, and 2,3-butanedione), and 2-year studies of (2,3-butanedione). ABAs have been linked to occupational exposure and human health effects including bronchiolitis obliterans. Animal studies are needed to determine the potential for human health effects to individual ABAs. The 2,3-butanedione and acetoin 90-day studies have been completed and reported. The 2-year studies of 2,3-butanedione have been started. The 2,3-pentanedione 90-day study is currently in the exposure generation and monitoring phase. The contract also includes testing ortho-phthalaldehyde (OPA) in 90-day studies which were completed in FY-09. OPA is being utilized as a replacement for the known rodent carcinogen gluteraldehyde therefore animal toxicity data is needed to determine potential for human heal effects with OPA. The contract includes 90-day studies of p-chloro-a,a,a-trifluorotoluene (PCTFT). PCTFT is used extensively in the synthesis of a number of organic chemicals and there is concern with its increased use that there will be enhanced release to the atmoshphere. The 90-day study has been completed and reported. Keywords lung burden, fibrosis, toxicity and carcinogenicity, metal working fluids, abrasive blasting agents, artificial butter flavorings, antimony trioxide, ortho-phthalaldehyde