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一种体外方法的进一步验证,该方法可减少通过大鼠皮肤测量化学物质吸收时对体内研究的需求。

Further validation of an in vitro method to reduce the need for in vivo studies for measuring the absorption of chemicals through rat skin.

作者信息

Scott R C, Batten P L, Clowes H M, Jones B K, Ramsey J D

机构信息

Metabolism and Pharmacokinetics Section, ICI Central Toxicology Laboratory, Near Macclesfield, Cheshire, U.K.

出版信息

Fundam Appl Toxicol. 1992 Nov;19(4):484-92. doi: 10.1016/0272-0590(92)90085-v.

Abstract

Current requirements for the registration of agrochemicals, particularly in the U.S.A., often require the provision of dermal absorption data. In this process the rat is often used and complex in vivo studies, using large numbers of animals, are performed. We have compared the data obtained from in vivo and in vitro dermal absorption studies using eight pesticides with a range of physicochemical properties. Measurements were made of the 14C-labeled pesticides which could be washed from the skin, were associated with (on/in) skin, or absorbed through the skin following dermal applications in vivo and in vitro at various time points over a 24-hr exposure period. Good agreement was found between the amounts washed from and associated with the skin in vivo and in vitro. Over the time period 4-24 hr after application the in vitro experiments predicted the in vivo absorption within a factor of 2-3. These results show that, with a range of pesticide molecules, the in vitro method accurately predicted in vivo absorption supporting the utilization of the in vitro method for risk assessment from exposure to pesticides and other chemicals.

摘要

目前,尤其是在美国,农用化学品注册的要求通常需要提供皮肤吸收数据。在此过程中,常使用大鼠并开展复杂的体内研究,需要使用大量动物。我们比较了使用8种具有一系列物理化学性质的农药,通过体内和体外皮肤吸收研究获得的数据。在24小时暴露期内的不同时间点,对经皮应用后可从皮肤洗去、与皮肤相关联(在皮肤表面/皮肤内)或经皮肤吸收的14C标记农药进行了测量。体内和体外实验中从皮肤洗去的量以及与皮肤相关联的量之间有良好的一致性。在施用后4 - 24小时期间,体外实验预测的体内吸收在2至3倍的范围内。这些结果表明,对于一系列农药分子,体外方法能准确预测体内吸收情况,这支持将体外方法用于评估接触农药和其他化学品的风险。

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