title: Percutaneous permeation of N,N-diethyl-m-toluamide (DEET) from commercial mosquito repellents and the effect of solvent.
abstract: N,N-Diethyl-m-toluamide (DEET), the active ingredient in many commercial mosquito repellents, is thought to be responsible for a wide range of local and systemic adverse reactions following its use. Many investigators have studied the dermal absorption of pure DEET; however, there is only one report in the literature on the absorption of DEET from commercial mosquito repellents and the effect of concentration of DEET on its absorption through skin. The first objective of the present study was to evaluate the permeation characteristics of DEET from four commercial products, Everglades (95%), Repel Deerhunters (52.25%), Off Skintastic (6.65%), and Skedaddle (6.2%), as compared to pure DEET (approximately 100%). The second objective was to study the effects of ethanol, the solvent for DEET, on the permeation of DEET and investigate its potential for enhancing the dermal absorption of DEET. Permeation studies of DEET from commercial mosquito repellents and from solutions containing various percentages of ethanol were conducted across human skin using an infinite dose technique with a Franz diffusion cell. Permeation parameters such as steady-state flux (Jss), lag time (tL), diffusion coefficient (D), permeability (P), and skin/ vehicle partition coefficient (K) were obtained from the permeation profiles in each case. The cumulative amount of DEET permeated can be ranked according to the following order: neat DEET (100%) = Everglades (95%) > Repel (52.25%) > Skedaddle (6.2%) = Off Skintastic (6.65%). Pure DEET exhibited the highest flux value of 63.20 +/- 24.52 micrograms/cm2-h, while Off Skintastic had the lowest value of 21.12 +/- 14.75 micrograms/cm2-h. The tL and D values for each of the products were similar to that of pure DEET. The total amount of DEET permeated from 30-45% ethanolic solutions at the end of 36 h was significantly higher than that from pure DEET and from the 60-90% ethanolic solutions. The Jss, P, and K values of DEET from the 30-45% ethanolic solutions were significantly higher than those from the 75-90% ethanolic solutions, while the tL and D values were similar for each solution. Therefore, there is potential for significant absorption of DEET after the dermal application of commercial mosquito repellents, and ethanol, used as a solvent, may enhance the permeation of DEET.
authors.affiliation: Department of Pharmaceutical Sciences, Medical University of South Carolina, Charleston 29425, USA.
authors.forename: J
authors.initials: J
authors.lastname: Stinecipher
authors.forename: J
authors.initials: J
authors.lastname: Shah
mesh_terms: D000704:Analysis of Variance; D003671:DEET / Q000378:metabolism*; D004058:Diffusion; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D000431:Ethanol / Q000494:pharmacology*; D006801:Humans; D066298:In Vitro Techniques; D007302:Insect Repellents / Q000378:metabolism*; D011358:Product Surveillance, Postmarketing; D012867:Skin / Q000378:metabolism*; D012869:Skin Absorption / Q000187:drug effects*; D012997:Solvents / Q000494:pharmacology*
chemical_list: D007302:Insect Repellents; D012997:Solvents; D003671:DEET; D000431:Ethanol