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工业级1,3 - 二氯丙烯在大鼠体内的吸入药代动力学

Inhalation pharmacokinetics of technical grade 1,3-dichloropropene in rats.

作者信息

Stott W T, Kastl P E

出版信息

Toxicol Appl Pharmacol. 1986 Sep 30;85(3):332-41. doi: 10.1016/0041-008x(86)90340-6.

Abstract

Kinetic data on the uptake of vapors of technical grade 1,3-dichloropropene (DCP) and resultant cis- and trans-DCP blood concentrations were obtained in rats exposed to 30, 90, 300, or 900 ppm DCP for 3 hr. The uptake of DCP did not increase proportionately with increasing exposure concentration due to an exposure level-related decrease in the respiratory ventilatory frequency of rats exposed to greater than or equal to 90 ppm DCP and the saturation of metabolism of DCP by rats exposed to greater than or equal to 300 ppm DCP. Absorption of inhaled DCP occurred primarily in the lower respiratory tract, although a small amount of the chemical was absorbed via the nasal mucosa, a known target tissue of inhaled DCP in rats. Following absorption, both isomers of DCP were, at less than or equal to 300 ppm exposure levels, rapidly eliminated from the bloodstream (3-6 min half-life). In addition, data obtained in rats exposed to 300 ppm DCP revealed that this rapid elimination phase was followed by a slower elimination phase having a 33-43 min half-life. Rats exposed to 900 ppm vapors also eliminated DCP in a biphasic manner; however, in this case the blood half-life of DCP during the initial phase of excretion was 14 to 27 min. Exposure to 90 ppm DCP also produced a significant decrease in renal (31%) and hepatic (41%), but not pulmonary, nonprotein sulfhydryl content. Overall, these data demonstrated that a combination of saturable metabolism and chemically induced changes in respiration control DCP uptake and body burden in rats.

摘要

在暴露于30、90、300或900 ppm 1,3 - 二氯丙烯(DCP)3小时的大鼠中,获取了工业级DCP蒸气摄取的动力学数据以及由此产生的顺式和反式DCP血液浓度。由于暴露于大于或等于90 ppm DCP的大鼠呼吸通气频率出现与暴露水平相关的降低,以及暴露于大于或等于300 ppm DCP的大鼠对DCP的代谢饱和,DCP的摄取并未随暴露浓度增加而成比例增加。吸入的DCP主要在下呼吸道吸收,尽管少量该化学物质通过鼻黏膜吸收,鼻黏膜是大鼠吸入DCP的已知靶组织。吸收后,在暴露水平小于或等于300 ppm时,DCP的两种异构体均迅速从血液中消除(半衰期为3 - 6分钟)。此外,在暴露于300 ppm DCP的大鼠中获得的数据显示,在这个快速消除阶段之后是一个半衰期为33 - 43分钟的较慢消除阶段。暴露于900 ppm蒸气的大鼠也以双相方式消除DCP;然而,在这种情况下,排泄初始阶段DCP的血液半衰期为14至27分钟。暴露于90 ppm DCP还导致肾脏(31%)和肝脏(41%)而非肺部的非蛋白巯基含量显著降低。总体而言,这些数据表明,饱和代谢和化学诱导的呼吸变化共同控制大鼠体内DCP的摄取和身体负荷。

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