DISPOSITION OF XENOBIOTICS

对药代动力学因素的了解可以极大地帮助 毒性研究的剂量设定和 结果。 提名NTP测试的选定化学品 进行处置研究。 口服和皮肤吸收， 这些化学物质的分布、代谢和排泄是 根据需要在大鼠和其他物种中进行研究。 剂量效应 在处置是确定的，因为是路线的影响， exposure. 这些研究有助于预测慢性 exposure. 待研究的异生物质用放射性标记， 通过定制合成。 在给药后比较分布和排泄 多个剂量的静脉、口服和/或皮肤暴露，最高 为LD 50的1/10。 检查静脉给药后的处置 在治疗后的多个时间点。 排泄物，呼出的空气， 分析挥发物的放射性， 母体化合物和代谢产物， 层析 然后用化学方法表征金属 和/或酶促方法。 目前的工作重点是 柠檬醛（“柠檬油”），一种常见的调味品， 香味 我们已经描述了口服后其吸收的特征 和皮肤接触。 由于其挥发性， 剂量变得不可吸收。 一些柠檬醛 氧化脱羧并代谢成二氧化碳。 最 的柠檬醛通过尿液排出。 但部分 柠檬醛被代谢并进入合成代谢途径 有机体 5分钟内血液中不能检测到柠檬醛 静脉注射治疗 有许多代谢物，其中单- 和构成柠檬醛的两种异构体的二羧酸， 香叶醛和橙花醛及其葡糖苷酸和硫酸盐结合物 显得尤为重要。

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.