Increased 8-hydroxy-2 '-deoxyguanosine, a biomarker of oxidative DNA damage in rat urine following a single dermal dose of DEET (N,N-diethyl-m-toluamide), and permethrin, alone and in combination

Levels of the biomarker of DNA oxidative damage 8-hydroxy-2'-deoxyguanosine (8-OHdG) in rat urine following dermal exposure to DEET (N,N'-diethyl-m-to luamide) and permethrin, alone and in combination have been determined. A g roup of five rats for each time point were treated with a single dermal dos e of 400 mg/kg of DEET, 1.3 mg/kg of permethrin or their combination. Urine samples were collected 2, 4, 8, 16, 24, 48, and 72 h following application . Control urine samples of rats treated with ethanol were also collected at the same time intervals. Solid phase extraction coupled with high performa nce liquid chromatography (HPLC) with UV detection at 254 nm was used for d etermination of 2'-deoxyguanosine, and (8-OHdG). The limits of detection (L OD) were 0.5 ng of both 2'-deoxyguanosine and 8-OHdG. Their average percent age recoveries from urine samples were between 70-85%. A single dermal dose of DEET or in combination with permethrin significantly induced levels of (8-OHdG) that are excreted in the urine over the time course of the study c ompared to control urine samples. Permethrin did not cause significant incr ease in the amount of 8-OHdG in the urine. Levels of 8-OHdG in urine excret ed at 24 h were 1009 +/- 342, 1701 +/- 321, 1140 +/- 316, and 1897 +/- 231 ng following treatment with ethanol, DEET, permethrin, and DEET + permethri n, respectively. The results indicate that dermal administration of DEET co uld generate free radical species hence cause DNA oxidative damage in rats. (C) 2000 Published by Elsevier Science Ireland Ltd. All rights reserved.