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采用 OECD TG 428 方法评估农用喷雾干燥残留物质的经皮体外吸收(皮肤)

Assessing in vitro dermal absorption of dry residues of agrochemical sprays using human skin within OECD TG 428.

机构信息

Corteva Agriscience LLC, USA.

Bayer CropScience, France.

出版信息

Regul Toxicol Pharmacol. 2019 Aug;106:55-67. doi: 10.1016/j.yrtph.2019.04.016. Epub 2019 Apr 25.

Abstract

We describe a novel experimental method that mimics exposure to dried agrochemical residues on contact surfaces during re-entry into crops. It includes the creation of dry dislodgeable residues and subsequent transfer to human skin for in vitro measurement of dermal absorption within a standard Organisation for Economic Co-operation and Development test guideline (OECD TG) 428 study. A pre-determined volume of spray containing C-labelled active substance is transferred onto a polytetrafluorethylene-coated septum and air-dried. The septum is then gently placed onto the pre-wetted skin mounted in a flow-through Franz diffusion chamber. The septum is gently rotated thrice to transfer the dose. Preliminary tests determined transfer efficiency to ensure the appropriate test concentration on the skin. Then, a standard dermal absorption study is performed according to OECD TG 428. Results from 10 compounds indicate that the methodology can be robustly incorporated into a standard TG study. These data show that the dermal absorption from a dry dislodgeable residue is lower than that from the equivalent dose of the aqueous spray, regardless of formulation type or active substance. Studies following the scenario described above can be a suitable tool to better estimate dermal absorption from dry residues in re-entry worker and resident exposure assessment for agrochemicals.

摘要

我们描述了一种新颖的实验方法,可模拟在重新进入作物时接触表面上的干燥农用化学品残留的暴露情况。它包括创建干燥的可剥落残留,然后将其转移到人体皮肤上,以在经合组织(OECD)测试指南 428 号标准(OECD TG)研究中进行体外皮肤吸收测量。将包含 C 标记的活性物质的预定体积的喷雾转移到聚四氟乙烯涂层的隔膜上并风干。然后,将隔膜轻轻放置在预润湿的皮肤置于流通式 Franz 扩散室上。将隔膜轻轻旋转三次以转移剂量。初步测试确定了转移效率,以确保皮肤的适当测试浓度。然后,根据 OECD TG 428 进行标准皮肤吸收研究。来自 10 种化合物的结果表明,该方法可以可靠地纳入标准 TG 研究中。这些数据表明,无论制剂类型或活性物质如何,从干燥的可剥落残留中吸收的皮肤吸收量均低于等效剂量的水性喷雾。按照上述方案进行的研究可以成为更好地评估重新进入工人和居民接触评估中农用化学品干燥残留皮肤吸收的合适工具。

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