| Title: | In Vitro high-throughput toxicological assessment of E-cigarette flavors on human bronchial epithelial cells and the potential involvement of TRPA1 in cinnamon flavor-induced toxicity |
| Author(s): | Effah F; Elzein A; Taiwo B; Baines D; Bailey A; Marczylo T; |
| Address: | "Pharmacology Section, St George's University of London, Cranmer Terrace, SW17 0RE London, UK; UK Health Security Agency, Radiation, Chemical and Environmental Hazards, Chilton, Didcot, Oxfordshire OX11 ORQ, UK. Electronic address: Felix.effah@ukhsa.gov.uk. UK Health Security Agency, Radiation, Chemical and Environmental Hazards, Chilton, Didcot, Oxfordshire OX11 ORQ, UK. Physiology Section, St George's University of London, Cranmer Terrace, SW17 0RE London, UK. Infection and Immunity Institute, St George's University of London, Cranmer Terrace, SW17 0RE London, UK. Pharmacology Section, St George's University of London, Cranmer Terrace, SW17 0RE London, UK. UK Health Security Agency, Radiation, Chemical and Environmental Hazards, Chilton, Didcot, Oxfordshire OX11 ORQ, UK. Electronic address: tim.marczylo@ukhsa.gov.uk" |
| DOI: | 10.1016/j.tox.2023.153617 |
| ISSN/ISBN: | 1879-3185 (Electronic) 0300-483X (Linking) |
| Abstract: | "Electronic cigarettes (ECs) are considered a less hazardous alternative to tobacco smoking but are not harmless. Growing concerns about the safety profiles of flavors in e-liquids underpin the need for this study. Here, we screened 53 nicotine-free flavored e-liquids (across 15 flavor categories) across a 3-point concentration range (0.25%, 0.5%, and 1% v/v) in a high-throughput fashion in human bronchial epithelial (HBEC-3KT) submerged cell cultures to identify 'toxic hits' using in vitro endpoint assays comprising cell count, cell viability, and lactate dehydrogenase (LDH). We observed significant, dose-dependent adverse effects only with cinnamon, vanilla tobacco, and hazelnut e-liquids compared to media-only and PG/VG vehicle controls. Hence, we further analyzed these three flavors for their effects on HBEC-3KT proliferation, mitochondrial health, and oxidative stress. A significant decrease in cell proliferation after 36 h was observed for each e-liquid toxic hit compared to media-only and PG/VG controls. Hazelnut (at all concentrations) and vanilla tobacco (1%) increased cytoplasmic reactive oxygen species generation compared to media-only and PG/VG controls. Conversely, all three flavors at 0.5% and 1% significantly decreased mitochondrial membrane potential compared to PG/VG and media-only controls. Chemical analysis revealed that all three flavors contained volatile organic compounds. We hypothesized that the cytotoxicity of cinnamon might be mediated via TRPA1; however, TRPA1 antagonist AP-18 (10 muM) did not mitigate these effects, and cinnamon significantly increased TRPA1 transcript levels. Therefore, pathways mediating cinnamon's cytotoxicity warrant further investigations. This study could inform public health authorities on the relative health risks assessment following exposure to EC flavor ingredients" |
| Keywords: | Humans Bronchi Cell Count Cinnamomum zeylanicum *Electronic Nicotine Delivery Systems Epithelial Cells Flavoring Agents/adverse effects/toxicity TRPA1 Cation Channel E-cigerrette E-liquid Flavor Human lung Toxicity; |
| Notes: | "MedlineEffah, Felix Elzein, Atallah Taiwo, Benjamin Baines, Deborah Bailey, Alexis Marczylo, Tim eng Ireland 2023/08/19 Toxicology. 2023 Sep; 496:153617. doi: 10.1016/j.tox.2023.153617. Epub 2023 Aug 17" |
