Neurotoxicity Evaluation of N,N-Diethyl-m-toluamide (DEET) in Rats

Schoenig, Gerald P.; Hartnagel, Ralph E.; Schardein, James L.; Vorhees, Charles V.

doi:10.1006/faat.1993.1108

Cited by 28 publications

(15 citation statements)

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“…25,34 The enhanced disposition of DEET metabolites from concurrent skin application raised concerns for these DEET metabolites that may exert pharmacological and/or toxicological effects from prolonged exposure to DEET and oxybenzone. 8,25 Brain and kidney samples collected from this study also contained all DEET metabolites; ET was the predominant metabolite in these organs. However, concurrent application did not lead to significant increases in brain and kidney concentrations.…”

Section: Tissue Dispositionsmentioning

confidence: 79%

“…The pharmacokinetics and toxicology of DEET and oxybenzone applied alone have been reported in some previous studies. [8][9][10] Since concurrent skin application of repellents and sunscreens was rare in the past, studies were only carried out to assess concurrent use of DEET or oxybenzone in association with several specialty chemical substances pertinent to military and/or farming usages. 11,12 In addition, loss of Sun Protection Factor (SPF) of the sunscreens has been reported from mixing DEET-based repellents and commercial sunscreen products.…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2012

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Insect repellent N,N-diethyl-m-toluamide (DEET) and sunscreen oxybenzone have shown a synergistic percutaneous enhancement when applied concurrently. Both compounds are extensively metabolized in vivo into a series of potentially toxic metabolites: 2 metabolites of DEET, N,N-diethyl-m-hydroxymethylbenzamide (DHMB) and N-ethyl-m-toluamide (ET), and 3 metabolites of oxybenzone, 2,4-dihydroxybenzophenone (DHB), 2,2-dihydroxy-4-methoxybenzophenone (DMB), and 2,3,4-trihydroxybenzophenone (THB). In this study, the metabolites were extensively distributed following intravenous and topical skin administration of DEET and oxybenzone in rats. Combined application enhanced the disposition of all DEET metabolites in the liver but did not consistently affect the distribution of oxybenzone metabolites. The DHMB appeared to be the major metabolite for DEET, while THB and its precursor DHB were the main metabolites for oxybenzone. Repeated once-daily topical application for 30 days led to higher concentrations of DEET metabolites in the liver. Hepatoma cell studies revealed a decrease in cellular proliferation from all metabolites as single and combined treatments, most notably at 72 hours. Increased accumulation of DHMB and ET in the liver together with an ability to reduce cellular proliferation at achievable plasma concentrations indicated that simultaneous exposure to DEET and oxybenzone might have the potential to precipitate adverse effects in a rat animal model.

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Section: Tissue Dispositionsmentioning

confidence: 79%

Section: Introductionmentioning

confidence: 99%

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

et al. 2012

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“…Parameters evaluated included observations for clinical signs and measurements of body weight and food consumption. In addition, functional observational battery (FOB), thermal response test, and motor activity measurements were made at 1 h, 24 h, and 14 days following dose administration (Schoenig et al, 1993).…”

Section: Acute Neurotoxicity Studymentioning

confidence: 99%

“…The animals used in this study were second generation (F 2 ) offspring from the rat multigeneration reproductive toxicity study in which DEET was administered continuously over two generations at dietary concentrations of 0, 500, 2000, and 5000 ppm (Schoenig et al, 1993).…”

Section: Chronic Neurotoxicity Studymentioning

confidence: 99%

Deet

Sudakin

Osimitz

2010

Hayes' Handbook of Pesticide Toxicology

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“…Previous studies were carried out primarily to assess the pharmacokinetics and toxicology of DEET and oxybenzone from application of individual compounds , as the concurrent skin application of repellents and sunscreens was not common. There were studies evaluating the concurrent use of DEET or oxybenzone in association with several other chemicals that were specifically utilized for military or farming purposes .…”

Section: Introductionmentioning

confidence: 99%

Tissue disposition of the insect repellent DEET and the sunscreen oxybenzone following intravenous and topical administration in rats

Fediuk

Wang

Chen

et al. 2011

Biopharm. Drug Dispos.

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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.

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Neurotoxicity Evaluation of N,N-Diethyl-m-toluamide (DEET) in Rats

Cited by 28 publications

References 0 publications

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

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

Deet

Tissue disposition of the insect repellent DEET and the sunscreen oxybenzone following intravenous and topical administration in rats

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