title: Gulf War related exposure factors influencing topical absorption of 14C-permethrin.
abstract: Topical exposure to permethrin has often been implicated as a mitigating factor in the illnesses reported in Gulf War veterans. These studies were designed to assess the effect of co-exposure to low level sulfur mustard, JP-8 jet fuel, N,N-diethyl-m-toluamide (DEET) and fabric occlusion on the percutaneous absorption and skin disposition of topically applied 14C-permethrin (40 microg/cm(2)) in the isolated perfused porcine skin flap (IPPSF) model. Extent of dermal absorption in vehicle controls in the IPPSF was comparable to literature values for humans. These studies demonstrated a two-fold increased 14C-permethrin percutaneous absorption and almost three-fold increased penetration when JP-8 was present, compared to a one-third decreased permethrin flux in the presence of sulfur mustard. Complete occlusion slightly increased 14C-permethrin absorption, while occlusion with fabric showed no significant effect. A previously noted effect of DEET to inhibit permethrin absorption was still seen in the presence of sulfur mustard exposure. These studies suggest that co-exposure to JP-8 or sulfur mustard may modulate transdermal flux of 14C-permethrin. However, the JP-8 increase in absorption and penetration was less than the five-fold increase previously seen with arterial infusion of pyridostigmine bromide and diisopropylfluorophosphate in the IPPSF. The toxicologic significance of this moderate increase in permethrin absorption remains unclear.
authors.affiliation: Center for Chemical Toxicology Research and Pharmacokinetics, College of Veterinary Medicine, North Carolina State University, 4700 Hillsborough Street, Raleigh, NC 27606, USA. jim_riviere@ncsu.edu
authors.forename: Jim E
authors.initials: JE
authors.lastname: Riviere
authors.forename: Nancy A
authors.initials: NA
authors.lastname: Monteiro-Riviere
authors.forename: Ronald E
authors.initials: RE
authors.lastname: Baynes
mesh_terms: D000818:Animals; D002800:Cholinesterase Inhibitors; D003671:DEET / Q000633:toxicity; D003879:Dermatologic Agents / Q000494:pharmacology / Q000633:toxicity; D004781:Environmental Exposure / Q000009:adverse effects; D006801:Humans; D006838:Hydrocarbons / Q000633:toxicity; D066298:In Vitro Techniques; D007302:Insect Repellents / Q000633:toxicity; D007306:Insecticides / Q000493:pharmacokinetics / Q000633:toxicity*; D007531:Isoflurophate / Q000633:toxicity; D009151:Mustard Gas / Q000633:toxicity; D026023:Permethrin / Q000493:pharmacokinetics* / Q000633:toxicity*; D018923:Persian Gulf Syndrome / Q000139:chemically induced*; D012867:Skin / Q000187:drug effects / Q000378:metabolism; D012869:Skin Absorption / Q000502:physiology; D013552:Swine
chemical_list: D002800:Cholinesterase Inhibitors; D003879:Dermatologic Agents; D006838:Hydrocarbons; D007302:Insect Repellents; D007306:Insecticides; C098607:JP8 aviation fuel; D007531:Isoflurophate; D003671:DEET; D026023:Permethrin; D009151:Mustard Gas