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-toluamide) and permethrin, alone and in combination have been determined. A group of five rats for each time point were treated with a single dermal dose 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 performance liquid chromatography (HPLC) with UV detection at 254 nm was used for determination of 2'-deoxyguanosine, and (8-OHdG). The limits of detection (LOD) were 0.5 ng of both 2'-deoxyguanosine and 8-OHdG. Their average percentage 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 compared to control urine samples. Permethrin did not cause significant increase in the amount of 8-OHdG in the urine. Levels of 8-OHdG in urine excreted at 24 h were 1009+/-342, 1701+/-321, 1140+/-316, and 1897+/-231 ng following treatment with ethanol, DEET, permethrin, and DEET+permethrin, respectively. The results indicate that dermal administration of DEET could generate free radical species hence cause DNA oxidative damage in rats.
Abu-Qare
A
A
Department of Pharmacology and Cancer Biology, Duke University Medical Center, Durham, NC 27710, USA.
Abou-Donia
M
M
D000080242:8-Hydroxy-2'-Deoxyguanosine; D000287:Administration, Topical; D000818:Animals; D015415:Biomarkers; D002138:Calibration; D002851:Chromatography, High Pressure Liquid; D003671:DEET / Q000008:administration & dosage / Q000493:pharmacokinetics*; D004249:DNA Damage / Q000187:drug effects*; D003849:Deoxyguanosine / Q000031:analogs & derivatives* / Q000652:urine; D007302:Insect Repellents / Q000008:administration & dosage / Q000493:pharmacokinetics*; D007306:Insecticides / Q000008:administration & dosage / Q000633:toxicity*; D008297:Male; D010084:Oxidation-Reduction; D026023:Permethrin; D011722:Pyrethrins / Q000008:administration & dosage / Q000633:toxicity*; D051381:Rats; D017207:Rats, Sprague-Dawley
D015415:Biomarkers; D007302:Insect Repellents; D007306:Insecticides; D011722:Pyrethrins; D003671:DEET; D026023:Permethrin; D000080242:8-Hydroxy-2'-Deoxyguanosine; D003849:Deoxyguanosine