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.

Trans-resveratrol and beta-carotene from sunscreens penetrate viable skin layers and reduce cutaneous penetration of UV-filters

“…Benzophenone-3 was detected in plasma and urine after topical application of sunscreens (Fediuk et al, 2011(Fediuk et al, , 2010Janjua et al, 2008). Beyond compromising skin photoprotection, cutaneous penetration of UV-filters in viable skin layers can cause photosensitivity (Hanno et al, 2012) and increase the risk of toxic or allergic reactions (Yang et al, 2008).…”

Metabolic Disposition of the Insect Repellent DEET and the Sunscreen Oxybenzone Following Intravenous and Skin Administration in Rats

“…17 A total of 167 µL of DEET preparation and 500 µL of oxybenzone preparation were injected into the tail vein of the animals at 2 mg/kg DEET (group 1) and 2 mg/kg oxybenzone (group 2). 16…”

“…17 A total of 167 mL of DEET preparation and 500 mL of oxybenzone preparation were injected into the tail vein of the animals at 2 mg/kg DEET (group 1) and 2 mg/kg oxybenzone (group 2). 16 For single, 24-hour topical skin administration, DEET and oxybenzone standards were weighed and dissolved in anhydrous ethanol at a concentration of 120 mg/mL DEET and 48 mg/mL oxybenzone, either individually or in combination. Prior to administration, an area of 25 cm 2 (5 Â 5 cm) on the back of each study animal was shaved using an electric clipper.…”

“…The 3 study doses were 100 mg/kg or 4 mg/cm 2 DEET (group 3), 40 mg/kg or 1.6 mg/cm 2 oxybenzone (group 4), and combined 100 mg/kg DEET/40 mg/kg oxybenzone (group 5). 16 A total of 250 mL of test solution were measured and applied onto the skin surface using a pipette. The solution was carefully spread over the shaven skin area with a disposable pipette tip, and sufficient time for ambient evaporation of the solvent was allowed before the study rats were returned to their holding cages.…”

“…Previous studies in Sprague-Dawley rats also observed Cmax values of DEET and oxybenzone at 0.5 mg/mL and 2.5 mg/mL, respectively. 15,16 Hence, the objective of this study was to determine the potential metabolite disposition of high-dose DEET and oxybenzone following intravenous and topical skin administration in a rat model. We also performed in vitro hepatoma cell experiments with metabolite concentrations between 0.1 and 10 mg/mL to assess potential toxicity resulting from enhanced disposition of these metabolites in the rat liver.…”