Kinetic analysis on the skin disposition of cytotoxicity as an index of skin irritation produced by cetylpyridinium chloride: comparison of in vitro data using a three-dimensional cultured human skin model with in vivo results in hairless mice.
OBJECTIVE
The aim of this study was to kinetically and dynamically analyze in vitro cytotoxicity as an index of skin irritation by use of a three-dimensional cultured human skin model and to compare the in vitro assay data with data from living animals.


METHODS
A cationic surfactant, cetylpyridinium chloride (CPC), was selected as a model irritant. Living skin equivalent-high (LSE-high) and hairless mice were used for the in vitro and in vivo tests, respectively. Skin irritation dermatodynamics was evaluated by calorimetric thiazoyl blue (MTT) conversion assay both for in vitro and in vivo tests, whereas dermatokinetics of CPC in LSE-high and mouse skin were evaluated using HPLC.


RESULTS
The time course of cell viability in the skin after application of CPC to intact skin was distinctly different from that of stratum-corneum-stripped skin in both LSE-high and hairless mice. Biphasic behavior characterized by two first-order rates with an inflection time point was observed in intact skin, whereas cell viability monoexponentially decreased immediately after CPC application in stripped skin. The time courses of cell viability in the skin and dermatodynamics were closely related to that of dermatokinetics of CPC.


CONCLUSIONS
The present study demonstrates that the in vitro cytotoxic profile was similar to the in vivo cytotoxicity test and that dermatodynamics was related to dermatokinetics of CPC.
Faculty of Pharmaceutical Sciences, Josai University, 1-1, Keyakidai, Sakado, Saitama 350-0295, Japan.
Satoshi
S
Kano
Kenji
K
Sugibayashi
D000465:Algorithms; D000818:Animals; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D002594:Cetylpyridinium / Q000633:toxicity*; D002851:Chromatography, High Pressure Liquid; D020405:Dermis / Q000166:cytology / Q000187:drug effects; D003902:Detergents / Q000633:toxicity*; D000078404:Epidermal Cells; D004817:Epidermis / Q000187:drug effects; D006801:Humans; D007509:Irritants / Q000633:toxicity*; D007700:Kinetics; D008297:Male; D051379:Mice; D008812:Mice, Hairless; D012867:Skin / Q000378:metabolism* / Q000473:pathology*; D013056:Spectrophotometry, Ultraviolet; D013385:Succinate Dehydrogenase / Q000378:metabolism; D013778:Tetrazolium Salts; D013844:Thiazoles
D003902:Detergents; D007509:Irritants; D013778:Tetrazolium Salts; D013844:Thiazoles; D002594:Cetylpyridinium; D013385:Succinate Dehydrogenase; C022616:thiazolyl blue