CHEMISTRY SUPPORT SERVICES TO THE ENVIRONMENAL TOXICOLOGY PROGRAM

该项目的目标是为国家毒理学计划（NTP）的危害识别活动提供支持，这些活动旨在预防因环境暴露于化学或物理制剂而引起的疾病或不良影响。毒性测试是公共卫生研究的一个重要方面，因为它有助于确定对人类健康有害的化学品。需要进行适当的化学分析，以确保在毒性研究中，试验种属以规定的剂量浓度暴露于规定的化学品。该合同通过提供所研究化学品的特征、所施用剂量水平的确认和内部剂量确定，有助于毒性研究提供癌症风险增加沿着其他毒理学结果的证据。这些信息对于评价毒性试验和得出关于研究化学品在试验种属中的潜在毒性的合理科学结论至关重要，并最终支持国家毒理学计划和其他联邦机构的风险评估工作。根据该合同提供的内部剂量信息，可以对人类进行推断，以便公众能够充分了解接触所研究的化学品所产生的风险因素。 在2010财年，超过280项任务已经开始，执行和/或完成，以支持NTP和NTP的研究和测试协议。为了支持NTP膳食锌致癌研究，开发了ICP-OES方法来分析全血中的锌。分析了2年致癌研究中的140份样品的Zn、Cu和Fe。锌浓度范围为~5.5至~9.0，与锌剂量无关。为支持NTP生殖毒性研究，采购了15种邻苯二甲酸酯，并使用超高效液相色谱（UPLC）、气相色谱、元素分析和红外光谱进行了全面表征。今年的表征工作主要集中在该组中的大支链邻苯二甲酸酯上。这些物质是支链邻苯二甲酸酯的复杂混合物，其平均链长反映了它们的命名。开发并验证了两种不同饲料溶剂中邻苯二甲酸二（2-乙基己基）酯的给药制剂和剂量分析方法。为了支持致癌计划，对苯乙烯丙烯腈三聚体进行了低水平杂质筛选，以寻找苯乙烯和丙烯腈单聚体和二聚体的存在。发现苯乙烯单体的浓度为230 ppm沿着，并含有痕量的二聚体。未检出丙烯腈（LOD = 80 ppm）。为了支持NTP霉菌计划，确定了合成脱氧雪腐镰刀菌烯醇（一种在谷物中发现的真菌毒素）的来源，这是NTP免疫毒理学计划的目标供试品。为了支持一项正在研究皮马印第安人糖尿病的研究，对从研究中收集的350份血清样本进行了总砷和有机砷分析。为支持NTP靶向试验计划，采购并表征了计划用于肝毒性试验的12种化学品中的4种。发现了一种常用剂量溶剂，并开发了一种给药每种化学品的配制方法。为支持大豆异黄酮研究，制备了阳性对照品炔雌醇制剂，并进行了促子宫试验分析。

The goal of this project is to provide support of National Toxicology Program (NTP) hazard identification activities targeted toward the prevention of diseases or adverse effects caused by environmental exposure to chemical or physical agents. Toxicity testing is an important aspect of public health research in that it serves to identify chemicals that are hazardous to human health. Proper chemical analyses are required to ensure that, in toxicity studies, the test species are exposed to the prescribed chemicals at the specified dose concentrations. This contract contributes to the ability of toxicity studies to provide evidence of heightened cancer risk along with other toxicological outcomes, by providing characterization of the chemicals studied, confirmation of the dose levels administered, and internal dose determinations. This information is critical to evaluation of toxicity tests and development of sound, scientific conclusions about the potential toxicity of the study chemical in the test species and ultimately supports the risk assessment efforts of National Toxicology Program and other federal agencies. With internal dose information provided by this contract, extrapolations to humans can be made so that the public can be adequately informed about risk factors arising from exposure to studied chemicals. During FY10, more than 280 tasks were begun, performed, and/or completed in support of NTP and DIR research and testing protocols. In support of an NTP dietary zinc carcinogenesis study, an ICP-OES method was developed to analyze whole blood for Zn. 140 samples from the 2-year carcinogenesis study were analyzed for Zn, Cu, and Fe. Zn concentrations ranged from ~5.5 to ~9.0 regardless of Zn dose. In support of NTP reproductive toxicity studies, 15 phthalates were procured and comprehensively characterized using ultra high performance liquid chromatography (UPLC), gas chromatography, elemental analysis, and infrared spectroscopy. This year characterization efforts focused on the large, branched phthalates in the group. These substances are complex mixtures of branched phthalates, with chain length averages that reflect their nomenclature. Dose formulation and dose analysis methods were developed and validated for di-(2-ethylhexyl) phthalate in two different feed vehicles. In support of the carcinogenesis program, a low-level impurity screen was conducted on styrene acrylonitrile trimer looking for the presence of styrene and acrylonitrile mono- and dimers. Styrene monomer was found at a concentration of 230 ppm along with trace amounts of the dimer. Acrylonitrile was not detected (LOD = 80 ppm). In support of the NTP mold initiative, a source was identified to synthesize deoxynivalenol, a mycotoxin found on grain, which is a target test article for the NTP immunotoxicology program. In support of a DIR study, which is looking at diabetes in a population of Pima Indians, 350 serum samples, collected from the study, were analyzed for total and organic arsenic. In support of the NTP targeted testing program, 4 of 12 chemicals scheduled for liver toxicity testing were procured and characterized. A common dose vehicle was found and a formulation method was developed to administer each chemical. In support of a soy isoflavone study, formulations of the positive control, ethinyl estradiol, were prepared and analyzed for use in a uterotropic assay.