The reduced risk mandate in the field of nicotine delivery has driven innovation and expansion in new technologies which requires rapid toxicological assessment to keep pace. These new products (e.g., electronic cigarettes and tobacco heating products), vary greatly in vapour/smoke composition and bring about new toxicological assessment challenges.

To address the demand for increased throughput and modernised testing approaches, we have employed the genotoxicity screening platform ToxTracker®, to assess biomarkers of DNA damage, protein misfolding, oxidative and cellular stress, across the categories of cigarette (1R6F), tobacco heating product (THP1.4) and electronic cigarette (ePen3). We have also used two common extraction matrices for each product; gas vapour phase (GVP) and aqueous extracts (AqE).

Our data demonstrated a significant reduction in biomarkers of cellular (Btg2) and oxidative stress (Blvrb & Srnx1) and cytotoxicity for THP1.4 compared to cigarette (> 72 % reduction oxidative stress, > 59 % cellular stress and > 75 % cytotoxicity), with further reductions for ePen3 over 1R6F (> 97 % reduction oxidative and cellular stress, > 95 % cytotoxicity), when normalised for nicotine. We also demonstrated that while GVP and AqE responded equally across endpoints for the reference combustible cigarette, GVP had significantly less potency than AqE for THP (> 45 %) and ePen3.

Our data support a reduction in biological effect consistent with a potential harm reduction of alternative nicotine delivery technologies when compared with traditional cigarettes. As we aim to provide products with increasingly reduced toxicant profiles in the future, we should be mindful of the make-up of the smoke/vapour/aerosol from the different product categories, as the relative contributions of the vapour and particular phases can drastically vary between them. Test matrices should be used alone or in combination to facilitate assessment of both the particulate and vapour phases (e.g., GVP in combination with total particulate matter (TPM) preparations), with consideration on what is most appropriate for the product categories being evaluated and compared.