CHEMISTRY SUPPORT SERVICES TO THE ENVIRONMENTAL TOXICOLOGY PROGRAM

环境毒理学计划的化学支持服务

• 批准号: 7789073
• 负责人: CLARK ALGAIER
• 金额: $ 481.45万
• 依托单位: MIDWEST RESEARCH INSTITUTE
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-09-30 至 2010-09-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7789073
• 关键词: CHEMISTRY; SUPPORT; SERVICES; ENVIRONMENTAL; TOXICOLOGY

In support of National Toxicology Program (NTP), in their efforts of toxicological evaluations of toxicants, we have completed nearly 100 chemistry tasks were performed during FY2009. Dental composites are complex mixtures containing an organic resin matrix, reinforcing inorganic filler and a silane-coupling agent. It has been shown that the compound like bisphenol A (BPA) and bis-GMA were present in saliva after placement of a specific dental sealant that are shown to posses estrogenic activity. In this regard biological (human urine and saliva) samples were received from three different places for the assay of analytes: BPA and its possible derivatives and metabolites bisphenol A glycerolate dimethacrylate (bis-GMA), bisphenol A dimethacrylate (BPADM), bisphenol A diglycidyl ether (BADGE), bisphenol A bis (2,3-dihydroxypropyl) ether (BPAHPE), and tri (ethylene glycol) dimethacrylate (TEGDMA)]. The development method included the determination of the lowest quantifiable matrix concentration using liquid chromatography with mass spectrometric detection (LC/MS) and evaluation of matrix interferences. In an ongoing support of NTP¿s new initiative called ¿High Throughput Screening (HTS) program¿ for the toxicity testing different tasks are in progress. During the Fiscal Year hundreds of chemicals were tested for solubility, prepared 10/20mM solutions and shipped to different labs for high through-put screening experiments. The compound tris(2-Chloroisopropyl)phosphate (TCPP: mixture of four isomers), a flame retardant added to flexible polyurethane foam used in home furnishings includes. Following studies were performed for this compound: a bulk chemical limited analysis, dose formulation development study in NTP-2000 & NIH-07 feeds and in 0.5%,a 14-Day palatability study on at 50,000; 40,000; 30,000 ppm (¿g/g of feed) concentration of TCPP in NTP-2000 and NIH-07 feeds; nih07 for both Wistar Han rats and B6C3F1 mice. In continues studies on Ionic Liquids (IL) in the current year conducted Dose Formulation Development study in water and Bulk Chemical Reanalysis for the following IL¿s: 1-butyl-1-methyl-pyrrolidinium chloride, 1-butyl-3-methyl-imidazonium chloride, 1-ethyl-3-methyl-imidazonium chloride, and N-butyl-pyridinium chloride. To support the carcinogenic evaluation of n n-Butyl glycidyl ether (BGE), a comprehensive chemical analysis and dose formulation development study were performed. In support of studies on natural produces, gum guggul extract (GGE), a mixture of several steroid-lipids isolated from the plant Commiphora mukul (gum guggul) of Indian origin, containing Z- and E- isomers of guggulsterone as major constituents. In support of NTP studies a method was developed and validated for the assay of GGE in corn oil formulations. In support of the internal staff support program for LUMI-CELL¿ ER assay international validation study chemicals were purchased, coded, and shipped to labs in Japan, Italy and USA. Under above staff support program different compounds were shipped to the lab for MCF-7 estrogen receptor cell proliferation assay as requested by the internal staff. Also under GenTox Testing program chemicals were shipped for salmonella testing. Additionally 25 compounds are procured, prepared solutions as per the requirement and shipped to the lab for hemotoxicity assay. Additionally in support of the of the internal staff support program the study was conducted to determine the peptidyl-α-amidating monooxygenase (PAM) activity in soluble and membrane fractions of 4-phenyl-3-butenoic acid (PBA) treated prostate cancer cell (PC-3) lysates. With the TNP-tripeptide as substrate, the two reaction products, glycine-extended intermediate (TNP-D-Tyr-Val-α-hydroxy-Gly) and the amidated TNP-dipeptide (TNP-D-Tyr-Val-NH2) were determined using HPLC-UV. From the product concentration results and the cell lysate protein concentrations, the specific activity, was determined. Animal room water testing was conducted annually. Peroxide test on n-Butylglycidylether was performed every three months. Every year disposal of chemical and of biological samples was conducted. Following posters were presented in the 48th Society of Toxicology meeting, held in Baltimore, MD, during 15-19, 2009: ¿ Analytical Method Validation of Tris(chloropropyl) phosphate, Mixture in NTP-2000 and NIH-07 Rodent Diets ¿ Analytical Method Validation of 2-Methoxy-4-nitroaniline in NTP-2000 and NIH-07 Rodent Diets ¿ Preliminary Palatability Testing of Tris (chloropropyl) phosphate (TCPP) in Wistar Han Rats and B6C3F1 Mice ¿ Analytical Method Development for the Extraction and Analysis of Tris(chloropropyl)phosphate, mixture, 1-Chloroacetone and N-Acetyl-L-Cysteine

在国家毒理学计划(NTP)的支持下，我们在2009财年完成了近100项化学任务，对毒物进行了毒理学评估。牙科复合材料是由有机树脂基质、增强无机填料和硅烷偶联剂组成的复杂混合物。已有研究表明，在放置具有雌激素活性的特定牙科封闭剂后，唾液中存在类似双酚A(BPA)和双GMA的化合物。在这方面，从三个不同的地方收到了生物(人体尿液和唾液)样本，用于分析分析物：双酚A及其可能的衍生物和代谢物双酚A甘油酸二甲基丙烯酸酯(BIS-GMA)、双酚A二甲基丙烯酸酯(BPADM)、双酚A二缩水甘油醚(BBGE)、双酚A双(2，3-二羟丙基)醚(BPAHPE)和三乙二醇二甲基丙烯酸酯(TEGDMA)]。建立的方法包括用液相色谱-质谱仪(LC/MS)测定最低可定量的基质浓度和评价基质干扰。在NTP？S的持续支持下，针对毒性测试的高通量筛选(HTS)计划的不同任务正在进行中。在本财年，数百种化学品进行了溶解度测试，制备了10/20 mm溶液，并运往不同的实验室进行高通量筛选试验。三(2-氯异丙基)磷酸化合物(TCPP：四种异构体的混合物)，是一种添加到用于家居用品的软质聚氨酯泡沫塑料中的阻燃剂。对该化合物进行了以下研究：在NTP-2000和NIH-07饲料中进行了批量化学限量分析，剂量配方开发研究，在0.5%饲料中进行了14天的适口性研究，在NTP-2000和NIH-07饲料中进行了50,000；40,000；30,000 ppm(g/g饲料)的TCPP浓度研究；在Wistar汉族大鼠和B6C3F1小鼠中进行了NiH07。在对离子液体(IL)的持续研究中，本年度进行了以下离子液体在水中的剂量配方开发研究和散装化学再分析[S]：1-丁基-1-甲基-吡咯烷氯、1-丁基-3-甲基咪唑氯、1-乙基-3-甲基咪唑氯和N-丁基-吡啶氯。为支持正丁基缩水甘油醚(BGE)的致癌评价，进行了全面的化学分析和剂量配方研制研究。为了支持对天然产物的研究，古尔古尔树胶提取物(GGE)是从印度起源的植物Commiphora Mukul(古尔古尔树胶)中分离出来的几种类固醇-脂的混合物，含有古古尔斯特酮的Z-和E-异构体作为主要成分。为了支持NTP研究，开发了一种测定玉米油配方中GGE的方法，并进行了验证。为了支持LUMI-CELL？ER分析的内部员工支持计划，国际验证研究化学品被采购、编码并运往日本、意大利和美国的实验室。在上述人员支持计划下，应内部工作人员的要求，将不同的化合物运往实验室进行MCF-7雌激素受体细胞增殖试验。此外，根据GenTox检测计划，化学品被运往沙门氏菌检测。此外，还采购了25种化合物，按要求配制溶液，运往实验室进行血液毒性检测。此外，为了支持内部工作人员支持计划，本研究还进行了4-苯基-3-丁烯酸(PBA)处理的前列腺癌细胞(PC-3)裂解物中的肽基酰化单加氧酶(PAM)活性测定。以TNP-三肽为底物，用高效液相-紫外检测法测定了甘氨酸延伸中间体(TNP-D-Tyr-Val-羟基甘氨酸)和酰胺化TNP-二肽(TNP-D-Tyr-Val-NH2)。 根据产物浓缩结果和细胞裂解产物蛋白浓度，确定了比活力。每年都会进行动物房间的水测试。正丁基缩水甘油醚每3个月进行一次过氧化氢试验。每年都要处理化学和生物样品。以下海报于2009年15日至19日在马里兰州巴尔的摩举行的第48届毒理学学会会议上公布： NTP-2000和NIH-07啮齿动物饲料中磷酸三(氯丙基)酯混合物的分析方法验证 NTP-2000和NIH-07啮齿动物饲料中2-甲氧基-4-硝基苯胺的分析方法验证 磷酸三(氯丙基)酯(TCPP)在Wistar汉族大鼠和B6C3F1小鼠中的初步适口性试验 磷酸三(氯丙基)酯、混合物、1-氯丙酮和N-乙酰基-L-半胱氨酸萃取分析方法的建立