Studies to Evaluate the Toxic Carcinogenic Potential of Test Agents

本合同的目标是为国家毒理学计划(NTP)的危险识别(或危险评估)活动提供支持，旨在预防因环境暴露于化学或物理制剂而导致的疾病或不良影响。该合同包括通过吸入暴露途径进行测试的各种测试材料和测试材料类别，其中一些是蒸汽，另一些是液体或固体气雾剂。这份合同包括评估6种磨料喷砂剂(ABA)的纤维化潜力和肺负荷的慢性前研究，这些喷砂剂包括喷砂、煤渣、石榴石、碎玻璃、钢砂和镜面赤铁矿。磨料喷磨剂因其硅的含量和作为晶态二氧化硅的替代品而对人类健康产生影响。为期14天的研究已经完成，并报告了除钢砂以外的所有ABA的研究。钢砂的研究已经被搁置，这取决于散装材料是否可以被碾磨以满足研究需要。已开始对喷砂和镜面赤铁矿进行为期39周的纤维形成研究。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、CImal 1070和TRIM VX)进行的为期14天和90天的毒性研究。MWF在职业环境中被广泛使用，并对使用它们的个人构成可能的治愈风险。14天的研究被取消，TRIM SC210、TRIM VX、Cimstar 3800和Syntillo 1023直接进入90天的研究，这些研究已经完成并得到报道。TRIM VX和Cimstar 3800为期两年的研究正在进行中。合同还包括为期14天和两年的三氧化二锑研究。三氧化二锑已被证明是一些啮齿动物的致癌物质；然而，需要利用更好的控制暴露和更多的物种来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。为期14天的研究已完成并报告，为期两年的研究于2008财年第四季度开始。该合同还包括为期90天的50纳米和1微米尺寸的C60富勒烯纳米材料的研究。纳米材料是新兴的新技术，很少或根本没有已知的毒性和致癌性研究；因此，对人类健康的潜在影响是未知的。这些研究已经完成并提交了报告。合同还包括测试两种人造黄油调味剂(ABAS、乙酸乙酯、2，3-丁二酮)在14天(乙酸乙酯)、90天(乙酸乙酯、2，3-丁二酮)和两年(2，3-丁二酮)的研究中的测试。ABAs与职业暴露和对人类健康的影响有关，包括闭塞性细支气管炎。需要进行动物研究，以确定对单个ABA的潜在人类健康影响。为期90天的2，3-丁二酮研究和14天的乙二酮研究已经完成。为期90天的乙炔研究和为期两年的2，3-丁二酮研究已经开始。合同还包括在为期90天的研究中测试邻苯二甲醛(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质丙醛的替代品，因此需要动物毒性数据来确定OPA对人类愈合的潜在影响。该合同包括为期90天的对氯-a，a，a-三氟甲苯(PCTFT)的研究。PCTFT被广泛用于合成一些有机化学品，人们对其使用量的增加感到关切，因为它将增加向大气层的释放。化学和暴露产生和监测阶段正在进行中，这项为期90天的研究计划于2010财年第一季度开始。 肺负荷；纤维化；毒性和致癌性；金属加工液；磨料；富勒烯；纳米材料；人造黄油调味料；三氧化二锑；邻苯二甲醛

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 have been put on hold depending upon whether the bulk material can be milled to meet study needs. Thirty-nine week fibrogenicity studies with blasting sand and specular hematite have been started. 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 2-year studies of Trim VX and Cimstar 3800 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 started in the 4th quarter of FY-08. The contract also includes 90-day studies of C60 fullerene nanomaterials of 50nm and 1 micron sizes. Nanomaterials are emerging new technologies with little or no known toxicity and carcinogenicity studies having been performed; therefore the potential for human health effects is unknown. The studies have been completed and reported. The contract also includes testing two artificial butter flavoring agents (ABAs, acetoin, 2,3-butanedione) in 14- day (acetoin), 90-day studies (acetoin, 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 neede to determine the potential for human health effects to individual ABAs. The 2,3-butanedione 90-day study and the 14-day acetoin studies have been completed. The 90-day studies of acetoin and 2-year studies of 2,3-butanedione ahve been started. 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 chemistry and exposure generation and monitoring phase are in progress and the 90-day study is scheduled to start the first quarter of FY10. Keywords lung burden, fibrosis, toxicity and carcinogenicity, metal working fluids, abrasive blasting agents, fullerenes, nanomaterials, artificial butter flavorings, antimony trioxide, ortho-phthalaldehyde