Osborne, R. Overview of Culture Models and Standardization. In Vitro Cell. Dev. Biol. - Animal. 1998. 34(3): 8-A. Part II. Abstract T-1 [CopyrightÓ 1998 by the Society of In Vitro Biology (formerly the Tissue Culture Association). Permission to reproduce on website by the copyright owner.]

Human skin and corneal models are proving useful in toxicology for investigation of mechanisms of epithelial response to chemical irritants and for prediction of human irritation to chemicals or products. Air-interfaced stratified epithelial cultures allow for topical application of test substances in their native form, modeling topical exposures in vivo. It is possible to detect in vitro cellular and tissue changes that are early steps in the process of inflammation mediators and cytokines, and disruption of barrier function. Five stages of standardization of human epithelial cultures are proposed: (1) standardization of manufacturing procedures (e.g. source of tissue, sterility and adventitious agent testing, reproducibility); (2) determination of the structure of the in vitro construct relative to the in vivo tissue (e.g. cell types, three-dimensional architecture, tissue-specific markers); (3) determination of the physiology of the in vitro construct relative to the in vivo tissue (e.g. barrier function, percutaneous absorption); (4) determination of the mechanisms of response to chemical irritants relative to in vivo (e.g. cytotoxicity, mediator and cytokine production, wound healing); and (5) validation of in vitro test results from cultures to in vivo irritant responses. It is proposed that consideration of these standardization factors will lead to mechanistically-sound in vitro tests for safety assessments, and also will make it possible to calibrate in vitro responses across different culture models.