A Vision for the Future: The impact of NAMs on the future of genotoxicity testing
The Research Institute for Fragrance Materials (RIFM) assesses genotoxicity risk as part of its Safety Assessment Program to ensure that everyone can safely enjoy their favorite fragranced products. (Meet and talk with Genotoxicity lead Yax Thakkar and other RIFM scientists this Wednesday at RIFM’s 1st Annual Science Symposium, a free virtual event.)
For more than a decade, RIFM has committed itself to avoid animal testing while maintaining a robust program for scientifically assessing the safety of fragrance materials. RIFM investigates New Alternative Methods (NAMs) as part of this process.
RIFM is currently studying NAMs along with a high-throughput screening assay that may help scientists avoid misleading-positive results commonly seen in in vitro (in Petri dish or test tube) tests:
- The 3D reconstructed micronucleus (3DRSMN)/CometAssay; and
- The hen’s egg micronucleus (HET-MN) test/chicken egg CometAssay (CEGA-Comet).
- Toxtracker as a high-throughput screening assay.
The 3DRSMN test uses human keratinocytes (a type of cell found in human skin) to test for the genotoxic effects post-exposure to a fragrance ingredient. Since the cells are cultured from real human skin, the test can simulate an in vivo (in the body) test.
The HET-MN test uses a leghorn chicken embryo to test for genotoxic effects. Since fertilized chicken eggs take 21 days to hatch, the test is conducted up to day 11, before the chicken embryo develops a fully formed nervous system, to avoid any possible discomfort.
The ToxTracker assay uses green fluorescent protein (GFP) reporters in mammalian stem cells to identify the mechanism of the genotoxic potential of compounds with high accuracy.
In trials, both models have reproduced the results of historical animal tests while negating the false positives seen in non-animal tests with scientific explanations supported to address false positives using the Toxtracker assay. As RIFM Senior Scientist Yax Thakkar, MS, who heads RIFM’s Genotoxicity endpoint, explains: “With the Seventh Amendment to the EU Cosmetics Directive, conducting in vivo studies for safety evaluation to support the safety of consumer products is banned. Current in vitro models have a higher rate of misleading positives; hence there is a need for biologically relevant application-based assays to support the safety of fragrance materials.”