Pharmacotoxicological applications of an equivalent dermis: three measurements of cytotoxicity |
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Authors: | C Augustin O Damour |
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Institution: | (1) Laboratoire des substituts cutanés (CNRS-URA 1341), Hôpital Edouard Herriot, 3 place d'Arsonval, Lyon, France |
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Abstract: | The legal procedure for evaluating the toxicity of cosmetic, household, chemical and pharmaceutical products is still the irritancy Draize test on rabbits. Various irritation tests are currently being developed as alternatives toin vivo animal testing. Ourin vitro model system is composed of 24 equivalent dermis (ED) comprising a chitosan-cross-linked collagen-glycosaminoglycan matrix populated by foreskin fibroblasts. In evaluating this system for irritancy testing, three different measures of toxicity were used: MTT (dimethylthiazol diphenyltetrazolium bromide) reduction, and lactate dehydrogenase and interleukin-6 release. The experiments described herein represent a preliminary evaluation to determine the usefulness and predictive value of our 24 ED kit as an alternative method for the prediction of human dermal reaction, versus three chemical products: cadmium chloride, lauryl sulfate, and benzalkonium chloride. Preliminary results suggest that the ED may be a usefulin vitro model for the prediction of cutaneous and ocular toxicity and allow the development of a 24-skin-equivalent kit realized by seeding human normal keratinocytes onto the equivalent dermis.Abbreviations ED
equivalent dermis
- ECM
extracellular matrix
- FCM
fibroblast culture medium
- LDH
lactate dehydrogenase
- IL-6
interleukin-6
- MTT
dimethylthiazol diphenyltetrazolium bromide |
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Keywords: | alternative methods cytotoxicity endpoints dermal irritation equivalent dermis MTT IL-6 LDH |
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