Publications : 2021

Kandarova H, Raabe H, Hilberer A, Choksi N, Allen D. Retrospective review on in vitro phototoxicity data generated in 3D skin models to support the development of new OECD test guideline. Poster presented at Society of Toxicology Annual Meeting, Virtual, March 2021.


Phototoxicity (also photo-irritation), is a light-induced skin reaction that occurs when photoreactive chemicals are activated to produce cytotoxic effects. Phototoxicity testing of chemicals is mostly conducted in vitro, following the methods described in the OECD test guideline (OECD TG 432), using the Balb/C 3T3 mouse fibroblast cell line. The test is highly sensitive, but low specificity has been reported in some studies (1). The test has also limitations with testing poorly soluble compounds. The use of 3D reconstructed human epidermis (RhE) tissue models has been proposed as the second tier in an integrated testing strategy to assess potential phototoxic activity, especially for topical exposures (e.g., chemicals, pesticides, cosmetics) (2). We collected published data on phototoxicity testing using various RhE models and protocols. The dataset contains more than 80 materials and over 800 entries utilizing five different RhE models. The analysis conducted on the datasets revealed, that despite some differences between the protocols (e.g., exposure times, dosing, solvents), the RhE models have potential not only to distinguish between phototoxic and non-phototoxic materials but also the potential to predict phototoxic potency as demonstrated in limited studies conducted in parallel to clinical studies in human volunteers. This database provides a valuable resource towards achieving regulatory acceptance of the method. This project was funded in whole or in part with federal funds from the National Institute of Environmental Health Sciences, National Institutes of Health, Department of Health and Human Services, under Contract No. HHSN273201500010C. References: 1. Lynch AM, Wilcox P. Review of the performance of the 3T3 NRU in vitro phototoxicity assay in the pharmaceutical industry. Exp Toxicol Pathol. 2011;63(3):209-14. 2. Liebsch et al. Development of a new in vitro test for dermal phototoxicity using a model of reconstituted human epidermis. ALTEX. 1997;14(4):165-174