In chemico, in vitro and in vivo comparison of the skin sensitizing potential of eight unsaturated and one saturated lipid compounds

• Published in: Regulatory toxicology and pharmacology 2017-11, Vol.90, p.262-276
• Main Authors: Kreiling, Reinhard, Gehrke, Helge, Broschard, Thomas H., Dreeßen, Birte, Eigler, Dorothea, Hart, David, Höpflinger, Veronika, Kleber, Marcus, Kupny, Joanna, Li, Qiang, Ungeheuer, Peter, Sauer, Ursula G.
• Format: Article
• Language: English
• Subjects: Allergens - immunology; Animal Testing Alternatives - methods; Animals; Biological Assay - methods; Cell Line; Classification and labelling of substances; Cosmetic Products Regulation; Dermatitis, Allergic Contact - etiology; Direct Peptide Reactivity Assay (DPRA); Guinea Pigs; Human cell line activation test (h-CLAT); Humans; In Vitro Techniques - methods; KeratinoSens™ assay; Lipids - chemistry; Lipids - immunology; Mice; Models, Biological; Non-animal test methods; Octanol-water partition coefficient (log Kow); Registration, Evaluation, Authorisation and Restriction of Chemicals (REACH); Risk Assessment; Skin - drug effects; Skin - immunology; Skin sensitisation; Skin Tests - methods; Solubility; Species Specificity
• ISSN: 0273-2300; 1096-0295
• DOI: 10.1016/j.yrtph.2017.09.023

The applicability of the Direct Peptide Reactivity Assay (DPRA), the KeratinoSens™ assay and the human cell line activation test (OECD Test Guidelines 442C, 442D, 442E) in predicting the skin sensitising potential of nine lipid (bio)chemicals was investigated. The results from the three assays were integrated using a published prediction model (PM), by which skin sensitisation is predicted if at least two of the three assays yield positive results. Of the eight test substances that were classified as non-sensitisers using available Guinea Pig Maximisation Test (GPMT) data, only five were correctly predicted as ‘negative’ in the PM. (However, only two were correctly predicted as ‘negative’ in the murine Local Lymph Node Assay.) The one lipid (bio)chemical that tested positive in the GPMT was also positive applying the PM. Based upon the outcome of the present study, lipid (bio)chemicals with a log Kow up to 7–8 appear amenable to the three assays. However, solubility problems, that were not evident initially, affected the performance of the DPRA. Further investigations are merited to address the conclusiveness of negative test results with concurrent lack of cytotoxicity in the in vitro assays, to evaluate if poorly soluble substances come into contact with the cells. •3 non-animal assays for skin sensitisation testing have been adopted by the OECD.•9 lipid (bio)chemicals were assessed in these 3 in chemico/in vitro assays.•The test results were integrated applying a published prediction model.•Compared to available guinea pig test data, the 3 assays were over-predictive.•Substances with log Kow up to 7–8 appear amenable to the three assays.