ABSORPTION, DISTRIBUTION, METABOLISM, AND EXCRETION (ADME) IN MAMMALS

保留字：代谢产物鉴别;核磁共振; HPLC;质谱法;吸收;分发;代谢、排泄;动力学; LSC;体内;体外;放射性标记化合物;皮肤;灌胃;第四章;吸入;质量平衡;富勒烯;胆碱、二甲基乙醇胺; 2 '，2''-二硫代双苯甲酰苯胺，2-羟基-4-甲氧基二苯甲酮，铬，钨。 该合同的目的是为国家毒理学计划（NTP）的危害评估活动提供支持，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。根据该合同进行的项目旨在调查环境，工作场所或消费品中常见的化学品的毒性的归宿（吸收，分布，代谢和排泄，或ADME）和机制。这些研究通常涉及使用放射性标记的化学品，以及NTP毒理学和致癌性研究中使用的动物种属和品系。这项工作开发的数据用于NTP研究的设计和解释。在过去的财政年度（2009年），根据该合同进行了涉及枯烯、二甲基乙醇胺（DMAE）、富勒烯、2 '，2''-二硫代双苯甲酰苯胺（DTBBA）和2-羟基-4-甲氧基二苯甲酮（HMB）的结局（体外和/或体内）的研究。此外，铬和钨（钨酸钠）项目报告已经定稿，项目官员接受了报告，并提交供纳入国家过渡规划电子数据库系统。涉及异丙苯和富勒烯的项目已经完成，承包者正在编写项目报告草稿，然后提交项目干事审查和修订。在表征DMAE的ADME及其与胆碱在啮齿动物中的相互作用方面取得了重大进展。DTBBA及HMB项目为本财政年度的新项目。DTBBA是一种高产化学品，用作橡胶胶溶剂，特别是在轮胎工业中。HMB在化妆品和防晒产品中用作紫外线过滤剂。人们担心暴露于这些化学品的人类可能会受到毒性影响。因此，正在对这两种化学品进行ADME研究，为其毒理学评价提供数据。

Keywords: Metabolite identification; NMR; HPLC; Mass spectrometry; Absorption; Distribution; Metabolism, Excretion; Kinetics; LSC; In vivo; In vitro; Radiolabeled compounds; Dermal; Gavage; IV; Inhalation; Mass balance; Fullerene; Choline, Dimethylethanolamine; 2',2'''-Dithiobisbenzanilide, 2-Hydroxy-4-methoxybenzophenone, Chromium, Tungsten. The goal of this contract is to provide support of National Toxicology Program (NTP) hazard assessment activities targeted toward the prevention of diseases or adverse effects caused by environmental exposure to chemical or physical agents. Projects conducted under this contract are designed to investigate the fate (absorption, distribution, metabolism, and excretion, or ADME) and mechanisms of toxicity of chemicals commonly found in the environment, workplace, or in consumer products. These studies usually involve the use of radiolabeled chemicals, as well as species and strains of animals used in NTP studies of toxicology and carcinogenicity. Data developed by this work are used in the design and interpretation of the NTP studies. In the past fiscal year (2009), studies involving the fate (in vitro and/or in vivo) of cumene, dimethylethanolamine (DMAE), fullerenes, 2',2'''-dithiobisbenzanilide (DTBBA), and 2-hydroxy-4-methoxybenzophenone (HMB), have been conducted under this contract. Additionally, the chromium and tungsten (sodium tungstate) project reports were finalized, accepted by the project officer and submitted for inclusion into the NTP electronic database system. The projects involving cumene and fullerenes were finished and the draft project reports are in preparation by the contractors, prior to submission to the project officer for review and revision. Major progress was made toward characterizing the ADME of DMAE and its interaction with choline in rodents. The DTBBA and HMB projects were new starts in this fiscal year. DTBBA is a high production chemical used as a peptizing agent for rubber, particularly in the tire industry. HMB is used as a UV filter in cosmetic and sunscreen products. There is concern for potential toxicity to humans exposed to these chemicals. Therefore, ADME studies are being conducted for both chemicals to provide data for their toxicological evaluation.