title: Evaluation of compounds as barriers to dermal penetration of organophosphates using acetylcholinesterase inhibition.
abstract: An efficient, objective method for evaluating the efficacy of barrier compounds in preventing dermal penetration of organophosphates (OP) in rabbits was developed using time-dependent reduction in erythrocyte (RBC) acetylcholinesterase (AChE) activity as an endpoint. Anesthetized rabbits, with or without a dermal application of a mixture of high- and low-molecular-weight polyethylene glycols (mean molecular weight of 540 daltons; PEG 540), were exposed to different percutaneous doses of 3 highly toxic OP compounds. Dose-response curves were generated for RBC AChE inhibition as a function of percutaneous dose for each OP test material over time. From data generated, a single dose of each OP was selected to challenge PEG-540-protected and unprotected animals to validate the method as a means of differentiating effective from ineffective barriers to skin penetration. Data for a complete evaluation of a PEG 540 test barrier application were obtained within 4 h and anesthesia was maintained for the entire period.
authors.affiliation: Battelle, Columbus, OH 43201-2693.
authors.forename: C T
authors.initials: CT
authors.lastname: Olson
authors.forename: P I
authors.initials: PI
authors.lastname: Feder
authors.forename: D W
authors.initials: DW
authors.lastname: Hobson
authors.forename: R C
authors.initials: RC
authors.lastname: Kiser
authors.forename: R L
authors.initials: RL
authors.lastname: Joiner
mesh_terms: D000110:Acetylcholinesterase / Q000378:metabolism*; D000818:Animals; D002619:Chemical Warfare Agents / Q000378:metabolism* / Q000633:toxicity; D002800:Cholinesterase Inhibitors / Q000633:toxicity*; D004912:Erythrocytes / Q000201:enzymology; D005260:Female; D007928:Lethal Dose 50; D008297:Male; D009943:Organophosphorus Compounds / Q000378:metabolism* / Q000633:toxicity; D011817:Rabbits; D012869:Skin Absorption / Q000187:drug effects*
chemical_list: D002619:Chemical Warfare Agents; D002800:Cholinesterase Inhibitors; D009943:Organophosphorus Compounds; D000110:Acetylcholinesterase