Systems toxicology assessment of a representative e-liquid formulation using human primary bronchial epithelial cells.

Introduction:
This article presents a case study on the assessment of the toxicity of flavoring substances commonly used in electronic cigarette (e-cigarette) liquids. The study aimed to develop a systems toxicology approach to evaluate the impact of these substances on human primary bronchial epithelial cells. The methodology involves the use of high-content screening assays and gene expression analysis.

Key Points:

* The study identified individual flavoring substances that potentially contribute greatly to the overall mixture effect (citronellol and alpha-pinene).
* alpha-pinene did not contribute to the overall mixture cytotoxicity, while most of the cytotoxic effect appeared to be attributable to citronellol, with the remaining substances contributing due to synergistic effects.
* The authors developed and used different scoring methods, including Tox-Score, Phenotypic Score, and Biological Impact Factor/Network Perturbation amplitude, to rank the substances based on cytotoxicity, phenotypic outcome, and molecular network perturbations.
* The study highlights the benefits of testing both individual flavoring substances and mixtures for e-liquid flavor assessment.
* The authors emphasized the importance of data sharing for the benefit of consumer safety.

Main Message:
The study presents a comprehensive systems toxicology approach to assess the toxicity of flavoring substances commonly used in e-cigarette liquids. The methodology involves the use of high-content screening assays and gene expression analysis to evaluate the impact of these substances on human primary bronchial epithelial cells. The study identified individual flavoring substances that potentially contribute greatly to the overall mixture effect and highlights the importance of testing both individual flavoring substances and mixtures for e-liquid flavor assessment. The authors emphasized the importance of data sharing for the benefit of consumer safety, which is crucial in ensuring the safety and quality of e-cigarette products. Overall, the study provides valuable insights into the toxicity assessment of flavoring substances in e-cigarette liquids and underscores the need for further research in this area.

Marescotti D, Mathis C, Belcastro V, et al. Systems toxicology assessment of a representative e-liquid formulation using human primary bronchial epithelial cells. Toxicology reports. 2020;7:67-80. doi:10.1016/j.toxrep.2019.11.016