Joint poster with DSM: Case study on process-related impurities in polymeric materials
In vitro assessment of skin sensitizing potential of process-related impurities in polymeric materials during product development.
Presented at 2022 ESTIV
Abstract
Andy Forreryd1, Stefan Kaiser2, Roman Goy2, Florian Glaus2, Ulrika Mattson1, Robin Gradin1, Henrik Johansson1
1 SenzaGen AB, 22381 Lund, Sweden
2 DSM Nutritional Products Ltd, 4303 Kaiseraugst, Switzerland
Skin sensitization testing represents a key toxicological endpoint during safety evaluation of ingredients intended for consumer products with topical exposure, both in a regulatory context and during product development, to early understand the toxicological profile of the end-product and potential impurities.
The inclusion of New Approach Methods (NAMs) for skin sensitization testing into OECD TGs have resulted in a broader acceptance of such methods as replacements to animal models. However, these methods are not universally applicable, and compounds with certain properties, such as lipophilicity, or of complex composition, are frequently considered outside the applicability domain.
GARDskin is a genomic-based next-generation in vitro assay for assessment of skin sensitizers progressing towards regulatory acceptance. The assay is highly sensitive, is compatible with a variety of solvents and has a demonstrated applicability for testing of lipophilic materials.
The aim of this study was to evaluate the skin sensitization potential of a lipophilic polymeric material (Mw > 2000g/mol) containing approximately 2% impurities, during product development. The polymeric material was initially flagged as a skin sensitizer. A preparative procedure was applied to purify the polymer from impurities, while generating enriched by-product fractions (oligomeric fraction, Mw: 500-1000 g/mol and small molecule fraction, Mw: <500 g/mol). The fractions were evaluated in GARDskin, using acetone or DMSO as solvents, and classified as skin sensitizers (by-products) and non-sensitizers (purified polymers, n=2), respectively, indicating that the impurities were responsible for the positive classification of the initial non-purified polymeric material.
In conclusion, the GARDskin protocol enabled for testing of the lipophilic materials, using a selection of solvents to increase solubility. Results from this study informed that actions to reduce concentration of impurities may be a useful strategy to prevent skin sensitization properties of the final end-product, highlighting the importance of skin sensitization testing during the production development.
