Combined exposure to DEET (N,N-diethyl-m-toluamide) and permethrin: pharmacokinetics and toxicological effects.

Permethrin and DEET are concurrently used for pests control inside homes, in public places, and in military shelters. Combined exposure to these compounds produced greater biochemical, behavioral, and metabolic alterations in animals compared to each individual compound. Concurrent application of DEET and permethrin induced urinary excretion of 3-nitrotyrosine and 8-hydroxy-2'-deoxyguanosine, markers of DNA damage and oxidative stress in rats, increased the release of rat brain mitochondrial cytochrome c, disrupted the blood-brain barrier (BBB) in rats, decreased m2 muscarinic acetylcholine receptor ligand binding density in rat brain, increased urinary excretion of 6 beta-hydroxycortisol, a marker CYP3A4 induction, altered sensorimotor and locomotor activities in rats, and changed in vivo and in vitro metabolism and pharmacokinetic profiles of the individual compound. These findings show that more research is needed to examine adverse effects of the combined use of DEET and permethrin on other biochemical/physiological system(s) and to predict mechanistic pathways for these effects, particularly mechanism of action at cellular and molecular levels and alterations of genes transcription.