Expansion of the Cosmetics Europe skin sensitisation database with new substances and PPRA data

• Published in: Regulatory toxicology and pharmacology 2022-06, Vol.131, p.105169-105169, Article 105169
• Main Authors: Hoffmann, Sebastian, Alépée, Nathalie, Gilmour, Nicola, Kern, Petra S., van Vliet, Erwin, Boislève, Fanny, Bury, Dagmar, Cloudet, Elodie, Klaric, Martina, Kühnl, Jochen, Lalko, Jon F., Mewes, Karsten, Miyazawa, Masaaki, Nishida, Hayato, Tam Brami, Mai Thanh, Varçin, Mustafa, Api, Anne Marie, Europe, Cosmetics
• Format: Article
• Language: English
• Subjects: Animal Testing Alternatives - methods; Animals; Cosmetics - toxicity; Databases, Factual; Dermatitis, Allergic Contact - etiology; Human reference data; Humans; LLNA; Local Lymph Node Assay; New approach methodologies; Next generation risk assessment; Skin; Skin sensitisation
• ISSN: 0273-2300; 1096-0295
• DOI: 10.1016/j.yrtph.2022.105169

The assessment of skin sensitisation is a key requirement in all regulated sectors, with the European Union's regulation of cosmetic ingredients being most challenging, since it requires quantitative skin sensitisation assessment based on new approach methodologies (NAMs). To address this challenge, an in-depth and harmonised understanding of NAMs is fundamental to inform the assessment. Therefore, we compiled a database of NAMs, and in vivo (human and local lymph node assay) reference data. Here, we expanded this database with 41 substances highly relevant for cosmetic industry. These structurally different substances were tested in six NAMs (Direct Peptide Reactivity Assay, KeratinoSens™, human Cell Line Activation Test, U-SENS™, SENS-IS, Peroxidase Peptide Reactivity Assay). Our analysis revealed that the substances could be tested without technical limitations, but were generally overpredicted when compared to reference results. Reasons for this reduced predictivity were explored through pairwise NAM comparisons and association of overprediction with hydrophobicity. We conclude that more detailed understanding of how NAMs apply to a wider range of substances is needed. This would support a flexible and informed choice of NAMs to be optimally applied in the context of a next generation risk assessment framework, ultimately contributing to the characterisation and reduction of uncertainty. •Expansion of skin sensitisation database with 41 relevant cosmetic ingredients.•Peroxidase Peptide Reactivity Assay added as further new approach methodology (NAM).•New substances could be tested technically, but were overpredicted by NAMs.•Better understanding of NAMs applicability to a wider substance range is required.•a flexible and informed use of NAMs in skin sensitisation risk assessment is needed.