DISPOSITION OF XENOBIOTICS

对药代动力学因素的了解可以极大地帮助 用于毒性研究和解释的剂量设置 结果。由NTP测试的选定化学品被提名 用于意向研究。吸收，包括口服和皮肤吸收， 这些化学物质的分布、新陈代谢和排泄是 根据需要在老鼠和其他物种中进行研究。剂量效应 在处置上是确定的，就像 曝光。这些研究有助于预测慢性前列腺癌的结果。 曝光。要研究的外源生物被放射性标记 通过定制合成。比较两组动物的分布和排泄量 几种剂量的口服和/或皮肤暴露，最高剂量 是半数致死剂量的十分之一。检查静脉注射后的处理情况 在治疗后的多个时间点。排泄物，呼出的空气， 并对挥发物进行放射性分析，将其分解为 母体化合物和代谢物通过有机溶剂提取和 层析法。代谢物然后用化学物质来表征 和/或酶促方法。目前的工作重点是 柠檬醛(“柠檬油”)的处置，一种常见的调味品和 香水。我们对其口服后的吸收进行了表征 以及皮肤暴露。因为它的挥发性，大部分的真皮 吸收剂量变得不可用。一些柠檬醛是 氧化脱羧基，代谢成二氧化碳。多数 柠檬醛在尿液中被排出。然而，一些 柠檬醛被代谢并进入人体的合成代谢途径。 有机体。5分钟内在血液中检测不到柠檬醛 进行静脉注射治疗。有许多代谢物，其单一的- 和组成柠檬醛的两个异构体的二羧酸， 天竺葵醛和纳豆醛，以及它们的葡萄糖醛酸苷和硫酸盐结合物 似乎特别重要。

An understanding of pharmacokinetic factors can assist greatly in both dosesetting for toxicity studies and in the interpretation of the results. Selected chemicals on-test by the NTP are nominated for disposition studies. The absorption, both oral and dermal, distribution, metabolism, and excretion of these chemicals are studied in rats and other species as needed. The effect of dose on disposition is determined, as is the effect of the route of exposure. These studies help to predict the results upon chronic exposure. Xenobiotics to be studied are radiolabeled with by custom syntheses. Distribution and excretion are compared after iv, oral, and/or dermal exposures at several doses, the highest being 1/10th of the LD50. Disposition after an iv dose is examined at multiple time points after treatment. The excreta, expired air, and volatiles are analyzed for radioactivity which is resolved into parent compound and metabolites by organic solvent extraction and chromatography. Metabolites are then characterized by chemical and/or enzymatic means. Current work has focused on the disposition of citral ("oil of lemon"), a common flavoring and fragrance. We have characterized its absorption after both oral and dermal exposures. Because of its volatility, much of a dermal dose becomes unavailable for absorption. Some of the citral is oxidatively decarboxylated and metabolized to carbon dioxide. Most of the citral is eliminated in the urine. However, some of the citral is metabolized and enters the anabolic pathways of the organism. No citral can be detected in the blood within 5 minutes of an iv treatment. There are many metabolites of which the mono- and di- carboxylic acids of the two isomers which make up citral, geranial and neral, and their glucuronide and sulfate conjugates appear to be especially important.