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。 剂量对 决定了处置，因为是路线的影响， exposure. 这些研究有助于预测 慢性暴露 待研究的异生物质用放射性标记， 14 C或3 H通过定制合成。 分布和排泄是 在几种剂量的静脉、口服和/或皮肤暴露后进行比较， 最高为LD 50的1/10。 静脉给药后的处置 在治疗后的多个时间点进行检查。 的 分析排泄物、呼出气体和挥发物的放射性 其通过有机溶剂分解为母体化合物和代谢物， 溶剂萃取和色谱法。 那么， 其特征在于化学和/或酶促方法。 电流 工作集中在柠檬醛（“柠檬油”）的处理上， 常见的调味品和香料。 完全吸收后， 经口接触，皮肤吸收良好，但挥发 使皮肤吸收不完全。 尿液是主要的传播途径 虽然胆汁排泄导致一些 肠肝循环以及一些粪便排泄。 氧化代谢导致大量 14CO2。 柠檬醛代谢迅速， 母体化合物在血液中检测10分钟内 局 至少有八种代谢物，其中一些 这是尿液和粪便中常见的。 葡糖苷酸和 似乎产生了硫酸盐缀合物。 正在进行研究， 进一步表征柠檬醛的代谢物。

An understanding of pharmacokinetic factors can assist greatly in both dose-setting 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 obtained upon chronic exposure. Xenobiotics to be studied are radiolabeled with 14C or 3H 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 in 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. It is completely absorbed after oral exposure, and well absorbed dermally, although volatilization makes dermal absorption incomplete. Urine is the major route of excretion although biliary elimination results in some enterohepatic circulation as well as some fecal excretion. Oxidative metabolism results in the production of substantial amounts of 14CO2. Citral is rapidly metabolized with little parent compound being detected in the blood within 10 minutes of administration. There are at least eight metabolites, some of which are common to urine and feces. Both glucuronides and sulphate conjugates appear to be produced. Studies are ongoing to further characterize the metabolites of citral.