The ‘BlueScreen HC’ assay as a decision making test in the genotoxicity assessment of flavour and fragrance materials

Etter, Sylvain; Birrell, Louise; Cahill, Paul A.; Scott, Heather; Billinton, Nick; Walmsley, Richard M.; Smith, Benjamin

doi:10.1016/j.tiv.2015.05.005

Cited by 10 publications

(3 citation statements)

References 37 publications

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“…methodologies employed in this study does not imply any endorsement or recommendation by the FDA CTP; there are other commercially available screening techniques that study DNA damage, which also support high-throughput in vitro screening for genotoxicity (Etter et al, 2015).…”

Section: Discussionmentioning

confidence: 99%

“…The positive results may also serve as complementary evidence to other available testing data, which can strengthen the evidence in the hazard characterization from DNA damage. It is also worth noting that the use of the specific commercial methodologies employed in this study does not imply any endorsement or recommendation by the FDA CTP; there are other commercially available screening techniques that study DNA damage, which also support high‐throughput in vitro screening for genotoxicity (Etter et al, 2015).…”

Section: Discussionmentioning

confidence: 99%

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In vitro and in silico genetic toxicity screening of flavor compounds and other ingredients in tobacco products with emphasis on ENDS

Hung

Savidge

et al. 2020

J of Applied Toxicology

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Electronic nicotine delivery systems (ENDS) are regulated tobacco products and often contain flavor compounds. Given the concern of increased use and the appeal of ENDS by young people, evaluating the potential of flavors to induce DNA damage is important for health hazard identification. In this study, alternative methods were used as prioritization tools to study the genotoxic mode of action (MoA) of 150 flavor compounds. In particular, clastogen-sensitive (γH2AX and p53) and aneugensensitive (p-H3 and polyploidy) biomarkers of DNA damage in human TK6 cells were aggregated through a supervised three-pronged ensemble machine learning prediction model to prioritize chemicals based on genotoxicity. In addition, in silico quantitative structure-activity relationship (QSAR) models were used to predict genotoxicity and carcinogenic potential. The in vitro assay identified 25 flavors as positive for genotoxicity: 15 clastogenic, eight aneugenic and two with a mixed MoA (clastogenic and aneugenic). Twenty-three of these 25 flavors predicted to induce DNA damage in vitro are documented in public literature to be in e-liquid or in the aerosols produced by ENDS products with youth-appealing flavors and names. QSAR models predicted 46 (31%) of 150 compounds having at least one positive call for mutagenicity, clastogenicity or rodent carcinogenicity, 49 (33%) compounds were predicted negative for all three endpoints, and remaining compounds had no prediction call. The parallel use of these predictive technologies to elucidate MoAs for potential genetic damage, hold utility as a screening strategy. This study is the first high-content and high-throughput genotoxicity screening study with an emphasis on flavors in ENDS products.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

In vitro and in silico genetic toxicity screening of flavor compounds and other ingredients in tobacco products with emphasis on ENDS

Hung

Savidge

et al. 2020

J of Applied Toxicology

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“…When RIFM’s safety assessment process was implemented, less than 50% materials had sufficient genotoxicity data to complete an endpoint safety evaluation. The BlueScreen HC has previously been shown to be a useful tool to prioritize fragrance and flavor materials, and it can be used to fill data gaps [ 11 ]. Therefore, the BlueScreen HC was selected as a high-throughput screening (HTS) assay that could support the safety evaluation process for fragrance materials.…”

Section: Introductionmentioning

confidence: 99%

The BlueScreen HC assay to predict the genotoxic potential of fragrance materials

et al. 2022

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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. A set of 371 fragrance materials was assessed in the BlueScreen HC assay along with existing or newly generated in vitro and in vivo genotoxicity data. Based on a weight-of-evidence approach, the majority of materials in the data set were deemed negative and concluded not to have the potential to be genotoxic, while only a small proportion of materials were determined to show genotoxic effects in these assays. Analysis of the data set showed a combination of high positive agreement but low negative agreement between BlueScreen HC results, in vitro regulatory genotoxicity assays, and higher-tier test results. The BlueScreen HC assay did not generate any false negatives, thereby providing robustness when utilizing it as a high-throughput screening tool to evaluate the large inventory of fragrance materials. From the perspective of protecting public health, it is desirable to have no or minimal false negatives, as a false-negative result may incorrectly indicate the lack of a genotoxicity hazard. However, the assay did have a high percentage of false-positive results, resulting in poor positive predictivity of the in vitro genotoxicity test battery outcome. Overall, the assay generated 100% negative predictivity and 3.9% positive predictivity. In addition to the data set of 371 fragrance materials, 30 natural complex substances were evaluated for BlueScreen HC, Ames, and in vitro micronucleus assay, and a good correlation in all three assays was observed. Overall, while a positive result may have to be further investigated, these findings suggest that the BlueScreen HC assay can be a valuable screening tool to detect the genotoxic potential of fragrance materials and mixtures.

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Early Drug Development

Valerio¹

2018

Early Drug Development

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The ‘BlueScreen HC’ assay as a decision making test in the genotoxicity assessment of flavour and fragrance materials

Cited by 10 publications

References 37 publications

In vitro and in silico genetic toxicity screening of flavor compounds and other ingredients in tobacco products with emphasis on ENDS

In vitro and in silico genetic toxicity screening of flavor compounds and other ingredients in tobacco products with emphasis on ENDS

The BlueScreen HC assay to predict the genotoxic potential of fragrance materials

Early Drug Development

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