Joint poster with Cargill: Case study on Hydrophobic Esters
The applicability of GARD®skin for assessing skin sensitization potential of hydrophobic esters during product development
Presented at Eurotox 2024
Conclusion
In conclusion, the inclusion of GARD®skin in the OECD test guidelines has expanded the applicability of NAMs for skin sensitization assessment.
This study demonstrates the applicability of the GARDskin assay to assess skin-sensitizing hazard of hydrophobic esters, which provides an ethical alternative to animal methods for safety assessment during product development.
Abstract
The field of skin sensitization assessment is rapidly evolving and the recent advancements in New Approach Methodologies (NAMs) has made it possible for the industry to perform in vitro skin ssensitization testing with good predictivity across a large chemical space. However, challenges remain for “difficult-to-test” chemicals, those with challenging physical/chemical properties or of Unknown or Variable composition, Complex reaction products or Biological materials (UVCBs), which are often outside the applicability domain of conventional cell-based assays. GARDskin (OECD TG 442E) is a genomic-based assay with demonstrated applicability to “difficult-to-test” substances.
The aim of this study is to assess the skin sensitization potential of two ester substances of biological origin, substance A and B, using the GARDskin assay. These substances are very hydrophobic and fall outside of the applicability domain of the conventional in vitro assays.
Both substances were successfully solubilised in cell media by utilizing a combination of heating, sonication, and selection of appropriate solvent vehicles (ethanol or acetone). No cytotoxicity was observed for either substance, thus 500 μM was chosen as the input concentration for cellular stimulations. GARDskin combines a genomic readout with machine learning to predict skin sensitizing hazard, where values above the threshold (DV=0) is predicted as skin sensitizing and below as non-sensitizing. Both substances resulted in negative mean Decisions Values and thus were classified as non-sensitizers in GARDskin (A: -1.54, B: -0.339).
In conclusion, with the inclusion of GARDskin into the OECD test guidelines, the range to where NAMs are appropriate has been increased. This study demonstrates the applicability of the GARDskin assay to assess skin sensitizing hazard of hydrophobic ethyl esters, which provides an ethical alternative to animal methods for safety assessment during product development.
Keywords: NAM, skin sensitization, difficult-to-test, UVCB, Applicability domain
