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Assessment of genotoxic potential of fragrance materials in the Chicken Egg Assays
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  • Yax Thakkar,
  • Kobets T.,
  • Anne Marie Api,
  • Jian-Dong Duan,
  • Gary Williams
Yax Thakkar
Research Institute for Fragrance Materials

Corresponding Author:ythakkar@rifm.org

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Kobets T.
New York Medical College
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Anne Marie Api
Research Institute for Fragrance Materials
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Jian-Dong Duan
New York Medical College
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Gary Williams
New York Medical College
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Abstract

The genotoxic and clastogenic/aneugeneic potentials of four α, ß-unsaturated aldehydes, 2-phenyl-2-butenal, nona-2-trans-6-cis-dienal, 2-methyl-2-pentenal and p-methoxy cinnamaldehyde, which are used as fragrance materials, were assessed in avian fetal livers using the Chicken Egg Genotoxicity Assay (CEGA) and the Hen’s egg micronucleus (HET-MN) assay, respectively. Selection of materials was based on their chemical structures and the results of their assessment in the regulatory in vitro and/or in vivo genotoxicity test battery. Three tested materials, 2-phenyl-2-butenal, nona-2-trans-6-cis-dienal and 2-methyl-2-pentenal, were negative in both, CEGA and HET-MN assays. These findings were congruent with the results of regulatory in vivo genotoxicity assays. In contrast, p-methoxy cinnamaldehyde, which was also negative in the in vivo genotoxicity assays, produced evidence of DNA damage, including DNA strand breaks and DNA adducts in CEGA, however, no increase in the micronucleus formation in blood was reported in the HET-MN study. Pretreatment with a glutathione precursor, N-acetyl cysteine, negated positive outcomes produced by p-methoxy cinnamaldehyde in CEGA, indicating that difference in response observed in the egg and rodent models can be attributed to rapid glutathione depletion. Additionally, the dosing protocols for both HET-MN and CEGA assays are different, which can also be an important contributing factor. Overall, our findings support the conclusion that CEGA and/or HET-MN can be considered as a potential alternative to animal testing as follow-up strategies for assessment of genotoxic potential of fragrance materials with evidence of genotoxicity in vitro.
01 Apr 2024Submitted to Environmental and Molecular Mutagenesis
03 Jul 20241st Revision Received
03 Jul 2024Submission Checks Completed
03 Jul 2024Assigned to Editor
03 Jul 2024Review(s) Completed, Editorial Evaluation Pending
18 Jul 2024Editorial Decision: Revise Minor
19 Aug 20242nd Revision Received
20 Aug 2024Submission Checks Completed
20 Aug 2024Assigned to Editor
20 Aug 2024Review(s) Completed, Editorial Evaluation Pending
20 Aug 2024Editorial Decision: Accept