Skin Sensitization Potency Assessments of Fragrance Materials using GARDskin Dose-Response

Joint poster with Research Institute for Fragrance Materials (RIFM),
Presented at the 2021 RIFM annual meeting & 2021 ACT annual meeting 

Mihwa Na, Ulrika Mattson, Robin Gradin, Henrik Johansson, Andy Forreryd, Anne Marie Api, Research Institute for Fragrance Materials, Inc., 50 Tice Boulevard, Woodcliff Lake, NJ, 07677, USA., SenzaGen AB, Lund, Sweden

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Conclusion

  • GARDskin Dose-Response closely approximated the potency categories of 9/12 fragrance materials tested.
  • Based on results from this dataset, GARDskin Dose-Response appears useful for potency assessment for weak sensitizers and may constitute a promising strategy for deriving a point of departure for quantitative risk assessments.

Abstract

Several New Approach Methods for hazard identification of skin sensitizers have been developed and incorporated as OECD Test Guidelines. However, the methods for potency assessment are still lacking. GARDskin (OECD TGP 4.106) was initially developed to identify skin sensitizers by monitoring transcriptional patterns of a biomarker signature in a dendritic like cell line.

The predictive capacity of GARDskin has been demonstrated previously, with 95.8% accuracy, 91.7% positive predictive value, and 100.0% negative predictive value (1 false positive, n=24) (Johansson, Gradin et al. 2019). To derive potency information, a strategy based on dose-response measurements in GARDskin, referred to as the GARDskin Dose-Response assay, has recently been proposed. The readout of the assay corresponds to the lowest concentration required to exceed the binary classification threshold in GARDskin. This concentration correlates with local lymph node assay (LLNA) EC3 and human no observed effect level (NOEL) values and linear regression models have been established to exploit these relationships for potency predictions.

In this blinded study, 12 fragrance materials (10 very weak sensitizers and 2 weak sensitizers) were evaluated in GARDskin Dose-Response. Results were evaluated by comparing predicted values to the reference potency categories. Three of the very weak sensitizers were predicted as non-sensitizers by GARDskin Dose-Response. For the remaining nine materials which were predicted as sensitizers, the predicted EC3 and NOEL values closely approximated the reference data for most materials. Based on results from this dataset, GARDskin Dose-Response appears useful for potency assessment for weak sensitizers and may constitute a promising strategy for deriving a point of departure for quantitative risk assessments.

A big step for non-animal methods in skin sensitization testing of medical devices

The new standard for skin sensitization ISO 10993-10 is freshly published and now includes in vitro methods – a big step for non-animal methods in skin sensitization testing of medical devices!

Our GARD assay is included in the standard, can be used with both saline and oil as extraction vehicles and provides human relevant results.

Learn how GARD can be used in your risk assessment

To learn how GARDskin Medical Device can be used in your risk assessment, contact our medical device and ISO expert Rose-Marie Jenvert, PhD on LinkedIn or mail: rose-marie.jenvert@senzagen.com.

Link to the standard: ISO 10993-10:2021: Biological evaluation of medical devices — Part 10: Tests for skin sensitization

SenzaGen and VitroScreen join forces

SenzaGen and VitroScreen have decided to join forces. The highly accurate and broadly applicable skin sensitization test platform GARD will be joined by a recognized pre-clinical CRO and leading in vitro research laboratory.

By joining forces, SenzaGen and VitroScreen will be able to combine their respective knowledge and expertise in novel and advanced biological systems, genomics, proteomics and machine learning to create innovative tools to help the industry transition to animal free testing with high performance human-based technology. SenzaGen and VitroScreen will provide a broadened in vitro service portfolio ranging from in vitro toxicology to preclinical efficacy testing.

About VitroScreen
For more than 20 years, VitroScreen has been leading innovation in pre-clinical testing based exclusively 3D human advanced tissue models offering their services to customers in the pharmaceutical, medical device, cosmetic, chemical, agrochemical and nutritional industries as more biologically relevant alternatives to animal testing. Based in Milan, Italy, VitroScreen provides pre-clinical research services organized in the following business units:

  • GLP certified facility for in vitro regulatory toxicology.
  • Pre-clinical in vitro efficacy testing platform on 3D advanced human tissue models.
  • In vitro Innovation Center with the VitroScreen ORA™ platform for the production of spheroids and organoids and microbiome research.
  • In vitro Consulting unit providing advice on regulatory in vitro toxicology strategies.

Learn more about VitroScreen at www.vitroscreen.com.