title: Assessment of the phototoxic potential of compounds and finished topical products using a human reconstructed epidermis.
abstract: The goal of this study was to design a model system for the assessment of phototoxic potential using a human reconstructed epidermis (HRE, SkinEthic Laboratories, Nice, France), by testing some representative phototoxic (P) and non-phototoxic (NP) compounds and finished topical products. The tissue response to 24-h application of 5-5000 microg/mL of the test agents in the presence and absence of UVA light was analyzed in terms of viability (Lactate Dehydrogenase release), pro-inflammatory activity (IL-8 release and mRNA expression) and morphology (histopathology). 8-Methoxypsoralen (P) and promethazin (P), but not sodium lauryl sulfate (NP) produced cytotoxicity concentration-response curves significantly different between irradiated and nonirradiated tissues. Only irradiated tissues showed morphological damage. Application of tetracyclin (P) in the culture medium, but not topically, induced similar signs of phototoxicity. 6-Methylcoumarine (weak P) was not cytotoxic, yet it increased IL-8 release and mRNA expression only following UVA irradiation. PUVA therapy creams containing 1% 8-Methoxy-psoralen (P) or coal tar (P) decreased viability and induced histologic damage in UVA-exposed tissues. In conclusion, the phototoxic potential of the tested agents was correctly predicted by using a tiered strategy that involves determining cytotoxicity, production of IL-8, and morphological damage following exposure of the HRE to the compounds and UVA light.
authors.affiliation: Preclinical Safety Department, Novartis Pharma AG, WSJ-386.1151, CH-4002 Basel, Switzerland.
authors.forename: J
authors.initials: J
authors.lastname: Medina
authors.forename: C
authors.initials: C
authors.lastname: Elsaesser
authors.forename: V
authors.initials: V
authors.lastname: Picarles
authors.forename: O
authors.initials: O
authors.lastname: Grenet
authors.forename: M
authors.initials: M
authors.lastname: Kolopp
authors.forename: S D
authors.initials: SD
authors.lastname: Chibout
authors.forename: A
authors.initials: A
authors.lastname: de Brugerolle de Fraissinette
mesh_terms: D002470:Cell Survival / Q000187:drug effects / Q000528:radiation effects; D017484:Dermatitis, Phototoxic / Q000209:etiology* / Q000473:pathology; D004817:Epidermis / Q000187:drug effects* / Q000473:pathology / Q000528:radiation effects*; D006801:Humans; D066298:In Vitro Techniques; D007509:Irritants / Q000633:toxicity*; D015603:Keratinocytes / Q000187:drug effects / Q000528:radiation effects; D018675:Toxicity Tests / Q000379:methods*; D014466:Ultraviolet Rays
chemical_list: D007509:Irritants