DEET (N,N-diethyl-m-toluamide) alone and in combination with permethrin increased urinary excretion of 6beta-hydroxycortisol in rats, a marker of hepatic CYP3A induction.
In this study, the ratio of 6beta-hydroxycortisol (6beta-OHF) to free cortisol (F) was determined in urine following a single dermal dose of 400 mg/kg of DEET (N,N-diethyl-m-toluamide), and 1.3 mg/kg of permethrin, alone and in combination, in rats. Urine samples were collected at 2, 4, 8, 16, 24, 48, and 72 h after application. Recoveries of 6beta-OHF and cortisol (F) from control urine samples were between 75 and 85%, with limits of detection at 30 and 10 ng/ml for cortisol and 6beta-OHF, respectively. A single dermal dose of DEET alone and in combination with permethrin significantly increased urinary excretion of 6beta-hydroxycortisol 24 h after dosing. Permethrin did not significantly alter the urinary excretion of 6beta-hydroxycortisol. These results indicate that DEET, alone and in combination with permethrin, increased urinary excretion of 6beta-OHF in rats following a single dermal dose application.
Abu-Qare
A W
AW
Department of Pharmacology and Cancer Biology, Duke University Medical Center, Durham, North Carolina 27710, USA.
Abou-Donia
M B
MB
D000818:Animals; D001189:Aryl Hydrocarbon Hydroxylases; D015415:Biomarkers; D002138:Calibration; D002851:Chromatography, High Pressure Liquid; D051544:Cytochrome P-450 CYP3A; D003577:Cytochrome P-450 Enzyme System / Q000096:biosynthesis*; D003671:DEET / Q000633:toxicity*; D006854:Hydrocortisone / Q000031:analogs & derivatives* / Q000652:urine*; D007302:Insect Repellents / Q000633:toxicity*; D007306:Insecticides / Q000633:toxicity*; D008297:Male; D010089:Oxidoreductases, N-Demethylating / Q000096:biosynthesis*; D026023:Permethrin / Q000633:toxicity*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015262:Xenobiotics / Q000378:metabolism
D015415:Biomarkers; D007302:Insect Repellents; D007306:Insecticides; D015262:Xenobiotics; D003671:DEET; D026023:Permethrin; C001380:6 beta-hydroxycortisol; D003577:Cytochrome P-450 Enzyme System; D001189:Aryl Hydrocarbon Hydroxylases; D051544:Cytochrome P-450 CYP3A; D010089:Oxidoreductases, N-Demethylating; D006854:Hydrocortisone