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

为了支持国家毒理学计划 (NTP)，在毒物毒理学评估方面，我们在 2009 财年完成了近 100 项化学任务。牙科复合材料是含有有机树脂基质、增强无机填料和硅烷偶联剂的复杂混合物。研究表明，在放置特定的牙科密封剂后，唾液中存在双酚 A (BPA) 和双-GMA 等化合物。在这方面，从三个不同的地方收集了生物（人尿和唾液）样本，用于分析物分析：BPA 及其可能的衍生物和代谢物双酚 A 甘油二甲基丙烯酸酯 (bis-GMA)、双酚 A 二甲基丙烯酸酯 (BPADM)。 , 双酚A二缩水甘油醚(BADGE), 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）] 开发方法包括使用液相色谱和质谱检测（LC/MS）测定最低可定量基质浓度以及评估基质干扰。 NTP??的新倡议称为 ¿高通量筛选 (HTS) 计划¿在本财年中，正在对数百种化学品进行溶解度测试，制备 10/20mM 溶液并运送到不同的实验室进行高通量筛选实验。 TCPP：四种异构体的混合物），一种添加到家具中使用的软质聚氨酯泡沫中的阻燃剂，针对该化合物进行了以下研究：批量化学有限分析、剂量配方开发研究。在 NTP-2000 和 NIH-07 饲料中，以及在 NTP-2000 和 NIH-07 饲料中 50,000；40,000 ppm（¿g/g 饲料）的 14 天适口性研究； Wistar Han 大鼠和 B6C3F1 小鼠继续对 Ionic 进行研究。液体（IL）今年在水中进行了剂量配方开发研究，并为以下 IL 进行了散装化学再分析。 s：1-丁基-1-甲基-氯化吡咯烷、1-丁基-3-甲基-氯化咪唑、1-乙基-3-甲基-氯化咪唑和N-丁基-氯化吡啶支持n的致癌性评估。正丁基缩水甘油醚 (BGE) 进行了全面的化学分析和剂量配方开发研究，以支持对天然产物、树胶的研究。 guggul 提取物 (GGE) 是从印度原产没药 (没药树) 植物中分离出来的几种类固醇脂质的混合物，含有 guggulsterone 的 Z 型和 E 型异构体作为主要成分。经验证可用于玉米油配方中的 GGE 测定，以支持 LUMI-CELL 的内部员工支持计划。根据上述员工支持计划，根据内部员工的要求，将不同的化合物运送到实验室进行 MCF-7 雌激素受体细胞增殖测定。此外，根据 GenTox 测试计划，还采购了 25 种化合物用于沙门氏菌测试，并根据要求准备了溶液并运送到实验室进行血液毒性测定。此外，为了支持内部员工支持计划，还进行了研究以确定。这4-苯基-3-丁烯酸 (PBA) 处理的前列腺癌细胞 (PC-3) 裂解物的可溶性组分和膜组分中的肽基-α-酰胺化单加氧酶 (PAM) 活性 以 TNP-三肽为底物，两种反应产物。 、甘氨酸延伸中间体 (TNP-D-Tyr-Val-α-羟基-Gly) 和酰胺化 TNP-二肽(TNP-D-Tyr-Val-NH2) 使用 HPLC-UV 测定。 根据产品浓度结果和细胞裂解物蛋白质浓度，每年进行一次对正丁基缩水甘油醚的过氧化物测试，每年进行一次化学和生物样品的处理。 2009 年 15 日至 19 日在马里兰州巴尔的摩举行的第 48 届毒理学会会议上展示了以下海报： ¿ NTP-2000 和 NIH-07 啮齿动物饲料中磷酸三（氯丙酯）混合物的分析方法验证 ¿ NTP-2000 和 NIH-07 啮齿动物饮食中 2-甲氧基-4-硝基苯胺的分析方法验证 ¿ Wistar Han 大鼠和 B6C3F1 小鼠磷酸三（氯丙基）酯 (TCPP) 的初步适口性测试 ¿ 磷酸三（氯丙酯）混合物、1-氯丙酮和 N-乙酰-L-半胱氨酸的提取和分析分析方法开发