title: Tissue disposition of the insect repellent DEET and the sunscreen oxybenzone following intravenous and topical administration in rats.
abstract: The insect repellent N,N-diethyl-m-toluamide (DEET) and sunscreen oxybenzone (OBZ) have been shown to produce synergistic permeation enhancement when applied concurrently in vitro and in vivo. The disposition of both compounds following intravenous administration (2 mg/kg of DEET or OBZ) and topical skin application (100 mg/kg of DEET and 40 mg/kg of OBZ) was determined in male Sprague-Dawley rats. Pharmacokinetic analysis was also conducted using compartmental and non-compartmental methods. A two-compartment model was deemed the best fit for intravenous administration. The DEET and oxybenzone permeated across the skin to accumulate in blood, liver and kidney following topical skin application. Combined use of DEET and oxybenzone accelerated the disappearance of both compounds from the application site, increased their distribution in the liver and significantly decreased the apparent elimination half-lives of both compounds (p < 0.05). Hepatoma cell studies revealed toxicity from exposure to all treatment concentrations, most notably at 72 h. Although DEET and oxybenzone were capable of mutually enhancing their percutaneous permeation and systemic distribution from topical skin application, there was no evidence of increased hepatotoxic deficits from concurrent application.
authors.affiliation: Faculty of Pharmacy, University of Manitoba, Winnipeg, MB R3E0T5, Canada.
authors.forename: Daryl J
authors.initials: DJ
authors.lastname: Fediuk
authors.forename: Tao
authors.initials: T
authors.lastname: Wang
authors.forename: Yufei
authors.initials: Y
authors.lastname: Chen
authors.forename: Fiona E
authors.initials: FE
authors.lastname: Parkinson
authors.forename: Michael P
authors.initials: MP
authors.lastname: Namaka
authors.forename: Keith J
authors.initials: KJ
authors.lastname: Simons
authors.forename: Frank J
authors.initials: FJ
authors.lastname: Burczynski
authors.forename: Xiaochen
authors.initials: X
authors.lastname: Gu
mesh_terms: D000287:Administration, Topical; D000818:Animals; D019540:Area Under Curve; D001577:Benzophenones / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics*; D045744:Cell Line, Tumor; D003671:DEET / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics*; D006207:Half-Life; D007275:Injections, Intravenous; D007302:Insect Repellents / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D013473:Sunscreening Agents / Q000008:administration & dosage / Q000493:pharmacokinetics*
chemical_list: D001577:Benzophenones; D007302:Insect Repellents; D013473:Sunscreening Agents; D003671:DEET; C005290:oxybenzone