Evaluation of compounds as barriers to dermal penetration of organophosphates using acetylcholinesterase inhibition.
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.
Olson
C T
CT
Battelle, Columbus, OH 43201-2693.
Feder
P I
PI
Hobson
D W
DW
Kiser
R C
RC
Joiner
R L
RL
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*
D002619:Chemical Warfare Agents; D002800:Cholinesterase Inhibitors; D009943:Organophosphorus Compounds; D000110:Acetylcholinesterase