title: In vitro phototoxicity testing: development and validation of a new concentration response analysis software and biostatistical analyses related to the use of various prediction models.
abstract: As demonstrated in several validation studies, the dermal phototoxic potential of chemicals in humans can be effectively assessed by in vitro methods. The core of these methods is to monitor dose-response curves of a chemical in the absence and presence of light, to quantify the difference between these two curves by appropriate measures (either the photo-irritancy factor [PIF], or the mean photo effect [MPE]), and to use these measures as predictors of in vivo phototoxicity. We present new concentration-response analysis software for in vitro phototoxicity testing, which runs on current personal computers, and takes into account all the limitations identified when using a former program. We also demonstrate the validity and robustness of this new software by applying it retrospectively to all data available from two phases of the EU/COLIPA validation trial for the 3T3 neutral red update in vitro phototoxicity test. Some frequently raised questions pertaining to the use of prediction models in phototoxicity testing are addressed, including: the necessity of using prediction models based on a cut-off; whether it is justifiable to use sharp prediction cut-off values; whether there is a biostatistical justification for the highest concentration of the test chemical; and whether repeated testing of a chemical is required.
authors.affiliation: Humboldt-Universität Berlin, Medizinische Fakultät (Charité), Institut für Biochemie, Monbijoustrasse 2, 10117 Berlin, Germany.
authors.forename: Björn
authors.initials: B
authors.lastname: Peters
authors.forename: Hermann-Georg
authors.initials: HG
authors.lastname: Holzhütter
mesh_terms: D016475:3T3 Cells / Q000187:drug effects / Q000378:metabolism; D000826:Animal Testing Alternatives / Q000379:methods*; D000818:Animals; D017484:Dermatitis, Phototoxic; D004305:Dose-Response Relationship, Drug; D006801:Humans; D007509:Irritants / Q000145:classification / Q000633:toxicity; D051379:Mice; D008962:Models, Theoretical; D009499:Neutral Red / Q000378:metabolism; D011237:Predictive Value of Tests; D012984:Software; D012985:Software Design; D015262:Xenobiotics / Q000145:classification / Q000633:toxicity
chemical_list: D007509:Irritants; D015262:Xenobiotics; D009499:Neutral Red