BIOAVAILABILITY AND TOXICITY STUDIES OF MICROENCAPSULATED CHEMICALS

微囊化学品的生物利用度和毒性研究

• 批准号: 3918626
• 负责人: R L MELNICK
• 金额: --
• 依托单位: NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/3918626
• 关键词: amines; drug administration routes; drug vehicle; gastrointestinal drug absorption; gastrointestinal toxin absorption; laboratory mouse; laboratory rat; molecular film; pharmacokinetics; toxicant interaction; toxin metabolism; trichloroethylene; vegetable oils

The National Toxicology Program is exploring the feasibility of adopting microencapsulation as an alternative means of incorporating volatile, reactive, and/or unpalatable chemicals into animal feed for toxicologic studies. Oral (dosed-feed) toxicology studies are performed on those chemicals which are demonstrated to be adequately stabilized in the microcapsules, but released into the gastrointestinal tract to allow biological availability. Trichlroethylene, 2-ethyhexanol, and methyl chloroform have been stabilized in microcapsules and evaluated for palatability and bioavailability in Fischer 344 rats. In each case, the absorption of the microencapsulated chemical was equivalent to that of the neat compound administered by gavage to Fischer 344 rats. In 14- day repeated-dose studies in F344 rats, similar toxic effects were produced by microencapsulated chemical given in feed as that of the neat chemical dissolved in corn oil administered by gavage. These studies indicate that microcapsulation can provide an excellent alternative method for studying the oral toxicological properties of volatile chemicals in laboratory animals. Future work will involve bioequivalence studies and toxicologic characterization of other microencapsulated chemicals.

国家毒理学计划正在探索 采用微胶囊作为一种替代手段 将挥发性、活性和/或令人不快的化学物质 用于毒理学研究的动物饲料。口服(剂量-饲料)毒理学 对这些化学物质进行的研究被证明是 在微囊中充分稳定，但释放到 胃肠道，以允许生物利用度。 三氯乙烯、2-乙基己醇和甲基氯仿已经被 稳定在微胶囊中，并评估适口性和 费希尔344只大鼠的生物利用度。在每种情况下，吸收 微囊化的化学物质的含量相当于 Fischer 344大鼠灌胃给药。在14年- 在F344大鼠身上进行的一天重复给药研究，类似的毒性效应是 由饲料中给予的微囊化化学物质生产，如 溶于玉米油的纯化学物质，通过灌胃给药。这些 研究表明，微胶囊可以提供极好的 口服毒理学研究的另一种方法 实验动物体内挥发性化学物质的含量。未来的工作将是 涉及生物等效性研究和毒理学表征 其他微胶囊化学品。