Tissue deposition of the insect repellent DEET and the sunscreen oxybenzone from repeated topical skin applications in rats.
Insect repellent N,N-diethyl-m-toluamide (DEET) and sunscreen oxybenzone are capable of enhancing skin permeation of each other when applied simultaneously. We carried out a cellular study in rat astrocytes and neurons to assess cell toxicity of DEET and oxybenzone and a 30-day study in Sprague-Dawley rats to characterize skin permeation and tissue disposition of the compounds. Cellular toxicity occurred at 1 µg/mL for neurons and 7-day treatment for astrocytes and neurons. DEET and oxybenzone permeated across the skin to accumulate in blood, liver, and brain after repeated topical applications. DEET disappeared from the application site faster than oxybenzone. Combined application enhanced the disposition of DEET in liver. No overt sign of behavioral toxicity was observed from several behavioral testing protocols. It was concluded that despite measurable disposition of the study compounds in vivo, there was no evidence of neurotoxicological deficits from repeated topical applications of DEET, oxybenzone, or both.
Faculty of Pharmacy, University of Manitoba, 750 McDermot Avenue, Winnipeg, MB R3E 0T5, Canada. xgu@cc.umanitoba.ca
Daryl J
DJ
Fediuk
Tao
T
Wang
Joshua E
JE
Raizman
Fiona E
FE
Parkinson
Xiaochen
X
Gu
D000287:Administration, Topical; D000818:Animals; D001253:Astrocytes / Q000187:drug effects; D001522:Behavior, Animal / Q000187:drug effects; D001577:Benzophenones / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics* / Q000633:toxicity; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D003671:DEET / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics* / Q000633:toxicity; D004357:Drug Synergism; D005260:Female; D005333:Fetus / Q000166:cytology; D006207:Half-Life; D007302:Insect Repellents / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics* / Q000633:toxicity; D008297:Male; D009474:Neurons / Q000187:drug effects; D010539:Permeability / Q000187:drug effects; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D012867:Skin / Q000187:drug effects* / Q000378:metabolism; D013473:Sunscreening Agents / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000633:toxicity; D014018:Tissue Distribution
D001577:Benzophenones; D007302:Insect Repellents; D013473:Sunscreening Agents; D003671:DEET; C005290:oxybenzone