Tag Archive for: fragrances

Practical application of the GARDskin Dose-Response assay to derive a No Expected Sensitization Induction Level (NESIL) value for confirmatory human patch studies to determine safe use level for novel fragrance ingredients

Presented at ACT 2023

T. Lindberg1, Christopher Choi2 , Andy Forreryd1, Ulrika Mattson1, Satoshi Sasaki3
1SenzaGen, Lund, Sweden; and 2Takasago International Corp, Rockleigh NJ, USA;3Takasago International Corp, Hiratsuka city, Kanagawa, Japan

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Summary

  • Combining the results from the GARD®skin Dose-Response assay with other NAMs enables weight-of-evidence based approaches to determine safe use levels of novel fragrance ingredients.
  • Based on the results from the weight-of-evidence approach, confirmatory human patch test and HRIPT are conducted. HRIPT is performed at the top concentration of 11250ug/cm2. Both results are negative, confirming the predicted NESIL-value from GARD®.

 

Abstract

Skin sensitization is one of the required endpoints for the development and registration of novel fragrance ingredients. Traditionally, assessment has been performed combining in vitro and in vivo assays, but recent developments has shifted to the use of New Approach Methodologies (NAMs), without need for in vivo methods. However, none of the proposed NAMs are currently validated for continuous potency predictions, which is required for quantitative risk assessments of novel fragrance ingredients.

The GARD®skin assay (OECD TG 442E) is a genomics-based assay for hazard identification of sensitizers. To meet the need for quantitative potency information, GARD®skin Dose-Response has been developed based on the validated protocols of GARD®skin and generates a dose-response curve to identify the lowest concentration of a test compound required to elicit a positive classification (cDV0-value). These values correlate significantly to LLNA EC3 and human NESIL values.

This study presents the use of the GARDskin Dose-Response assay to determine safe human user levels for one novel fragrance ingredient. The experimentally predicted NESIL value was determined to 37800µg/cm2. Using a weight-of- evidence approach mainly guided by the quantitative data from the GARDskin Dose-Response, confirmatory Human Repeated Insult Patch Testing (HRIPT) studies were conducted and at the tested concentrations, no sensitization reactions were observed. In conclusion, this study expands the toxicologist´s toolbox and illustrates the potential to use the GARDskin Dose-Response assay to derive NESIL values that are protective of human health, without having to rely on the Dermal Sensitization Threshold (DST) approach or reverting to traditional animal testing approaches.