Evaluation of the Tobacco heating System 2.2. Part 7: Systems toxicological assessment of a mentholated version revealed reduced cellular and molecular exposure effects compared with mentholated and non-mentholated cigarette smoke

Introduction:
This text provides an overview of a study evaluating the effects of exposure to tobacco heating system 2.2 (ThS2.2) aerosol and cigarette smoke (CS) on the respiratory system of rats. The study used a systems toxicology approach, which involves the use of transcriptomics, proteomics, and lipidomics to understand the molecular responses to exposure.

Key Points:

* The study exposed rats to three different concentrations of ThS2.2 aerosol and three different reference cigarettes for 90 days.
* The molecular responses in the respiratory nasal epithelium (RNE) and lung tissue were analyzed using transcriptomics, proteomics, and lipidomics.
* The RNE of rats exposed to CS showed more severe histopathological changes compared to rats exposed to ThS2.2 aerosol.
* The transcriptomics and proteomics data showed that exposure to CS resulted in extensive changes in both the RNE and lung tissue, while exposure to ThS2.2 aerosol resulted in very few changes.
* The network-based systems biology approach confirmed that exposure to CS resulted in network perturbations in the RNE and lung tissue, while exposure to ThS2.2 aerosol resulted in much lower overall network perturbation.
* The functional association clustering approach confirmed that exposure to CS resulted in the activation of immune-related, oxidative stress and xenobiotic response, and unfolded-protein response (UPR) pathways, while exposure to ThS2.2 aerosol had a much lower effect on these pathways.
* The lipidomics analysis revealed that CS exposure significantly affected sphingolipid metabolism, while ThS2.2 aerosol exposure had a much lower effect on sphingolipid metabolism.

Main Message:
The study demonstrates that exposure to ThS2.2 aerosol results in a much lower effect on the respiratory system compared to exposure to CS. The systems toxicology approach provides a more comprehensive and sensitive assessment of the effects of exposure, highlighting the potential benefits of ThS2.2 as a reduced risk product. The study also highlights the potential of this approach to identify exposure response markers and reduce the number of animal studies.

Kogel, Ulrike, Bjoern Titz, Walter K. Schlage, Catherine Nury, Florian Martin, alberto Oviedo, Stefan Lebrun, et al. “Evaluation of the Tobacco heating System 2.2. Part 7: Systems Toxicological assessment of a Mentholated Version Revealed Reduced Cellular and Molecular Exposure Effects Compared with Mentholated and Non-Mentholated Cigarette Smoke.” Regulatory Toxicology and Pharmacology 81 (November 2016): S123–38. https://doi.org/10.1016/j.yrtph.2016.11.001.