The genotoxicity of a library of 70 flavour and fragrance substances having a high proportion of in vivo and/or carcinogenicity test data has been assessed using the GADD45a-GLuc 'BlueScreen HC' genotoxicity assay, with and without exogenous metabolic activation. There are only limited genotoxicity and carcinogenicity study data for compounds in this applicability domain, but this study allowed the following conclusions: (i) The BlueScreen HC results are highly predictive of positive results from regulator-required in vitro genotoxicity assays for the test set of materials; the moderate negative predictivity of BlueScreen HC from the in vitro test set of material is mainly due to the high rate of false positive in regulatory in vitro mammalian tests. (ii) BlueScreen HC negative results are predictive of negative in vivo results and provide a specific prediction of in vivo genotoxicity assay results. (iii) In this applicability domain, which comprises a large proportion of relatively low molecular weight molecules, a 1mM testing limit maintains the sensitivity of the assay, and increases specificity. (iv) The predictive capacity and specificity to in vivo genotoxins and carcinogens, coupled to a microplate format with low compound requirement supports further investigation of the BlueScreen HC assay as a useful tool in prioritizing the assessment of new F&F materials and in filling data gaps on materials with no or limited regulatory test data for genotoxicity.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1016/j.tiv.2015.05.005 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
The BlueScreen HC assay to predict the genotoxic potential of fragrance materials.
Mutagenesis
April 2022
Research Institute for Fragrance Materials, Inc., 50 Tice Blvd, Woodcliff Lake, NJ 07677, United States.
BlueScreen HC is a mammalian cell-based assay for measuring the genotoxicity and cytotoxicity of chemical compounds and mixtures. The BlueScreen HC assay has been utilized at the Research Institute for Fragrance Materials in a safety assessment program as a screening tool to prioritize fragrance materials for higher-tier testing, as supporting evidence when using a read-across approach, and as evidence to adjust the threshold of toxicological concern. Predictive values for the BlueScreen HC assay were evaluated based on the ability of the assay to predict the outcome of in vitro and in vivo mutagenicity and chromosomal damage genotoxicity assays.
View Article and Find Full Text PDFIn ovo testing of flavor and fragrance materials in Turkey Egg Genotoxicity Assay (TEGA), comparison of results to in vitro and in vivo data.
Food Chem Toxicol
May 2018
Department of Pathology, New York Medical College, Valhalla, NY 10595, USA. Electronic address:
Genotoxicity of flavor and fragrance materials was assessed in Turkey Egg Genotoxicity Assay (TEGA) using P-nucleotide postlabeling (NPL) and comet assays to detect hepatic DNA adducts and strand breaks. Twenty materials having results in GADD45a-Gluc 'BlueScreen HC' genotoxicity assay, and standard in vitro and in vivo tests, were selected to evaluate the accuracy of TEGA. Quinoline (QUI) and 2-acetylaminofluorene (AAF) served as positive comparators.
View Article and Find Full Text PDFThe 'BlueScreen HC' assay as a decision making test in the genotoxicity assessment of flavour and fragrance materials.
Toxicol In Vitro
October 2015
Firmenich SA, Meyrin, Switzerland.
The genotoxicity of a library of 70 flavour and fragrance substances having a high proportion of in vivo and/or carcinogenicity test data has been assessed using the GADD45a-GLuc 'BlueScreen HC' genotoxicity assay, with and without exogenous metabolic activation. There are only limited genotoxicity and carcinogenicity study data for compounds in this applicability domain, but this study allowed the following conclusions: (i) The BlueScreen HC results are highly predictive of positive results from regulator-required in vitro genotoxicity assays for the test set of materials; the moderate negative predictivity of BlueScreen HC from the in vitro test set of material is mainly due to the high rate of false positive in regulatory in vitro mammalian tests. (ii) BlueScreen HC negative results are predictive of negative in vivo results and provide a specific prediction of in vivo genotoxicity assay results.
View Article and Find Full Text PDFAmes positive boronic acids are not all eukaryotic genotoxins.
Mutat Res Genet Toxicol Environ Mutagen
January 2015
Gentronix Ltd., BioHub at Alderley Park, Cheshire, SK10 4TG, United Kingdom; Faculty of Life Sciences, University of Manchester, M13 9PL, United Kingdom. Electronic address:
Boronic acids and their derivatives have been exploited for their pharmacological activity and their utility as intermediates in the synthesis of novel non-boron containing compounds. A recent study reported that boronic acids are bacterial mutagens. Here, results are reported from the testing of nine boronic acids using the pan-mechanistic eukaryotic GADD45a genotoxicity assays, BlueScreen HC and GreenScreen HC.
View Article and Find Full Text PDFThe BlueScreen-384 assay as an indicator of genotoxic hazard potential in early-stage drug discovery.
J Biomol Screen
April 2013
GlaxoSmithKline, Stevenage, Hertfordshire, UK.
High-throughput cell-based techniques that permit early detection of compound-induced genotoxic damage have recently become available. Methods based on induction of the GADD45a promoter are attractive because multiple intracellular mechanisms that detect genetic damage intersect at this checkpoint gene. Consequently, assays such as GreenScreen HC, which uses p53-competant human TK6 lymphoblastoid cells and a GADD45a-GFP reporter, have been developed.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!