Absorption and evaporation of N,N-diethyl-m-toluamide from human skin in vitro.
Absorption and evaporation of N,N-diethyl-m-toluamide from human skin in vitro.
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DOI：
10.1016/j.taap.2004.08.016
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发表时间：
2005-04
影响因子：
3.8
通讯作者：
A. Santhanam;M. Miller;G. Kasting
中科院分区：
文献类型：
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作者：
A. Santhanam;M. Miller;G. Kasting
在放置在通风橱或实验室工作台上的非闭塞 Franz 细胞中测量避蚊胺穿过分层厚度尸体皮肤的渗透性。将溶解在少量乙醇中并掺有14 C放射性标记的DEET以0.02至11000μg/cm 2 的剂量施用于皮肤。对于放置在工作台上的细胞，DEET 渗透更大，并且 72 小时后渗透的放射性百分比随着剂量逐渐增加，剂量高达 680 μg/cm2。在较高剂量下，它下降。渗透百分比范围从通风柜中剂量为 0.021 μg/cm2 的 11.5 ± 3.2% 到工作台上剂量为 260 μg/cm2 的 71.9 ± 5.5%。结果根据具有三个参数的扩散/蒸发模型进行解释：化学物质在上层角质层中的溶解度值，Msat；蒸发传质系数，kevap；和扩散特征时间 h2/D。通过将模型拟合到数据（标准化为通风柜环境）获得的参数为 Msat= 18 μg/cm2 和 kevap= 2.6 × 10−5cm/h。 h2/D 值从 DEET 剂量为 25 μg/cm2 时的 16 小时降低到 1480 μg/cm2 时的 10 小时，这与在此剂量范围内皮肤渗透性增加约 1.5 倍一致。这种效果通过另一项研究得到证实，其中用增加量的未标记DEET预处理的皮肤样品被洗涤并用14 C-苯甲醇重新添加。随着避蚊胺用量的增加，苯甲醇的渗透率出现小幅（1.7 倍）但显着的增加。因此，避蚊胺提高了其自身以及另一种化合物的皮肤渗透率，但效果不大，对于与避蚊胺共同施用的化合物来说不太可能是主要问题。
The penetration of DEET through split-thickness cadaver skin was measured in non-occluded Franz cells placed either in a fume hood or on a laboratory workbench. DEET, dissolved in a small volume of ethanol and spiked with14C radiolabel was applied to skin at doses from 0.02 to 11000 μg/cm2. DEET penetration was greater for cells placed on the workbench, and the percentage of radioactivity penetrated after 72 h increased gradually with dose, for doses up to 680 μg/cm2. At higher doses, it declined. Percent penetration ranged from 11.5 ± 3.2% for a dose of 0.021 μg/cm2in the fume hood to 71.9 ± 5.5% for a dose of 260 μg/cm2on the workbench. Results were interpreted in terms of a diffusion/evaporation model having three parameters—a solubility value for the chemical in the upper stratum corneum, Msat; a mass transfer coefficient for evaporation, kevap; and a characteristic time for diffusion, h2/D. The parameters obtained from fitting the model to the data (normalized to the fume hood environment) were Msat= 18 μg/cm2and kevap= 2.6 × 10−5cm/h. The value of h2/D decreased from 16 h at a DEET dose of 25 μg/cm2to 10 h at 1480 μg/cm2, consistent with an increase in skin permeability of about 1.5-fold over this dose range. This effect was confirmed by means of an additional study in which skin samples pretreated with increasing amounts of unlabeled DEET were washed and redosed with14C-benzyl alcohol. A small (1.7-fold), but significant, increase in benzyl alcohol penetration with increasing amount of DEET was obtained. Thus, DEET enhanced its own skin permeation rate as well as that of another compound, but the effect was modest and not likely to be a major concern for compounds coadministered with DEET.