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

The study in question is a high-content and high-throughput genotoxicity screening study focusing on flavors in Electronic Nicotine Delivery Systems (ENDS) products. The researchers used a combination of in vitro (conducted in a laboratory setting using test tubes, petri dishes, etc.) and in silico (computer-based) methods to predict the genotoxicity and carcinogenic potential of various flavors.

In vitro DNa damage assays were performed using the MultiFlow® assay, which identified 25 flavors positive for genotoxicity: 15 clastogenic (causing DNa breaks), eight aneugenic (interfering with chromosome separation), and two with a mixed mode of action (Moa). These 25 flavors, when compared with in silico clastogenicity models and public literature, showed a high concordance of up to 83%, increasing confidence in prioritizing potentially genotoxic compounds for further investigation.

Guaiacol, one of the flavors tested, raised health concerns due to its positive clastogenicity result without metabolic activation in the in vitro assay and in silico clastogenicity and carcinogenicity models. Caryophyllene oxide and methylbenzaldehyde, however, were not included in the Tox21 (a toxicology data sharing program) analysis, leaving their genotoxicity potential less clear.

In silico quantitative structure-activity relationship (qSaR) models were also used to predict genotoxicity and carcinogenic potential. Four rodent carcinogenicity models were employed to assess carcinogenicity. Expert knowledge assessments were conducted to revise any inconclusive results, ensuring the accuracy of the predictions.

Overall, this study aimed to provide a better understanding of the genotoxic and carcinogenic potential of various flavors in ENDS products, which could contribute to developing safer tobacco products and informing regulatory decisions.

hung Ph, Savidge M, De M, Kang JC, healy SM, Valerio LG. In vitro and in silico genetic toxicity screening of flavor compounds and other ingredients in tobacco products with emphasis on ENDS. Journal of applied toxicology : JaT. 2020;40(11):1566-1587. doi:10.1002/jat.4020