In vitro percutaneous penetration of organophosphorus compounds using full-thickness and split-thickness pig and human skin.
Organophosphorus compounds (OPs), such as pesticides and chemical warfare agents like sarin (GB), soman (GD) and VX, are highly toxic compounds. The OP vapours and their liquid forms are readily absorbed through the skin, therefore, protecting the skin of people who are potentially exposed to these agents is crucial. The development of effective countermeasures relies on a better knowledge of the percutaneous penetration of such molecules. The purpose of this present study is to determine the in vitro percutaneous penetration parameters of two pesticides DSM and DFP, as potential simulants of V and G agents, respectively, using four in vitro systems: full-thickness and split-thickness human abdominal and pig-ear skin membranes mounted on static diffusion cells. Based on the toxicokinetic parameters of the percutaneous penetration of DSM and DFP, we demonstrated that (a) pig-ear skin is a relevant model to predict the in vitro human skin permeability taking into account a 2-fold difference between these two species (b) both full and split-thickness skin membranes could be used indiscriminately, (c) DSM and DFP would be appropriate surrogates for V and G agents to perform skin permeation studies.
Vallet
V
V
Department of Toxicology, Centre de Recherche du Service de Santé des Armées, 24 avenue des maquis du Grésivaudan, 38702 La Tronche cedex, France. vvallet@crssa.net
Cruz
C
C
Josse
D
D
Bazire
A
A
Lallement
G
G
Boudry
I
I
D000005:Abdomen; D000328:Adult; D000818:Animals; D002619:Chemical Warfare Agents / Q000378:metabolism; D002800:Cholinesterase Inhibitors / Q000378:metabolism; D004423:Ear; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D007531:Isoflurophate / Q000378:metabolism*; D008875:Middle Aged; D063086:Organothiophosphates / Q000378:metabolism*; D010575:Pesticides / Q000378:metabolism*; D012867:Skin / Q000378:metabolism*; D012869:Skin Absorption; D013552:Swine
D002619:Chemical Warfare Agents; D002800:Cholinesterase Inhibitors; D063086:Organothiophosphates; D010575:Pesticides; D007531:Isoflurophate; C030064:demeton-S-methyl