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| NIOSH Home > Safety and Health Topics >Skin Exposures and Effects >Occupational & Environmental Exposures of Skin to Chemicals- 2005> Abstracts |
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Disposition of DEET after topical application to human skin in vitro
A. Santhanam, M.A. Miller, G.B, Kasting* Objective
This study was conducted as part of a broader project to develop a predictive diffusion model for the disposition of volatile compounds on skin. The motivation for studying DEET (the insect repellent N,N-diethyl-m-toluamide) was that a considerable body of in vivo data are available to which the results may be compared. Methods
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 with Results
DEET penetration was greater for cells placed on the workbench, and the percentage of radioactivity penetrated after 72 hours 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/cm2 in the fume hood to 71.9 ± 5.5% for a dose of 260 µg/cm2 on 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/cm2 and kevap = 2.6 ´ 10–5 cm/h. The value of h2/D decreased from 16 h at a DEET dose of 25 µg/cm2 to 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 with 14C-benzyl alcohol. A small (1.7-fold), but significant increase in benzyl alcohol penetration with increasing amount of DEET was obtained. Conclusions
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. The diffusion model successfully described the study results and is presently being extended to include other volatile permeants.
Content last modified: 17 May 2005 |