Percutaneous penetration and absorption of parathion using human and pig skin models in vitro and human skin grafted onto nude mouse skin model in vivo.
This study determined and compared the percutaneous penetration and absorption of an organophosphorus (OP) pesticide, parathion (PA), using three experimental skin models: namely the human abdominal- and pig-ear skin in vitro models and the Human Skin grafted onto a nude mouse (HuSki) in vivo model. The percentage of topically applied dose absorbed and the doses present in the stratum corneum and skin were systematically determined at 24 h under similar experimental conditions. The three experimental skin models were first compared. Then, the advantages of the HuSki model for in vivo PA skin absorption studies were evaluated compared with the pig in vivo model previously used by others. Lastly, the relevance of each skin model to predict the permeability of human skin to PA in vivo was assessed by comparing our results with previously published in vivo human volunteer values. It was demonstrated that (a) pig-ear skin is relevant for predicting the in vitro human abdominal skin absorption taking into account a 2-3 times higher skin permeability to PA, (b) using ethanol as the vehicle, the absorption of PA was 4-5 times higher in the HuSki model than in the pig model but supports the usefulness of the HuSki model to easy mass balance studies, (c) both human in vitro and HuSki models closely predict the in vivo human volunteer absorption at 24 h when acetone is used as a vehicle but the HuSki model overcomes the known limitations of in vitro models for studying the fate of PA in the different skin layers after topical application.
Boudry
I
I
Département de Toxicologie, Centre de Recherches du Service de Santé des Armées, 24 Avenue du Maquis du Grésivaudan, BP87, F-38702 La Tronche Cedex, France. iboudry@crssa.net
Blanck
O
O
Cruz
C
C
Blanck
M
M
Vallet
V
V
Bazire
A
A
Capt
A
A
Josse
D
D
Lallement
G
G
D000096:Acetone; D000818:Animals; D003627:Data Interpretation, Statistical; D000431:Ethanol; D006801:Humans; D066298:In Vitro Techniques; D007306:Insecticides / Q000493:pharmacokinetics*; D008566:Membranes / Q000378:metabolism; D051379:Mice; D008819:Mice, Nude; D010278:Parathion / Q000493:pharmacokinetics*; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics; D012867:Skin / Q000473:pathology; D012869:Skin Absorption / Q000502:physiology*; D016038:Skin Transplantation / Q000502:physiology*; D012997:Solvents; D013552:Swine; D014183:Transplantation, Heterologous
D007306:Insecticides; D019275:Radiopharmaceuticals; D012997:Solvents; D000096:Acetone; D000431:Ethanol; D010278:Parathion