In vitro toxicological evaluation of aerosols generated by a 4th generation vaping device using nicotine salts in an air-liquid interface system
Abstract Background Electronic cigarettes (EC) have gained popularity, especially among young people, with the introduction of fourth-generation devices based on e-liquids containing nicotine salts that promise a smoother vaping experience than freebase nicotine. However, the toxicological effects o...
| Main Authors: | , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
BMC
2024-02-01
|
| Series: | Respiratory Research |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s12931-024-02697-2 |
| _version_ | 1827326454232252416 |
|---|---|
| author | Clément Mercier Jérémie Pourchez Lara Leclerc Valérie Forest |
| author_facet | Clément Mercier Jérémie Pourchez Lara Leclerc Valérie Forest |
| author_sort | Clément Mercier |
| collection | DOAJ |
| description | Abstract Background Electronic cigarettes (EC) have gained popularity, especially among young people, with the introduction of fourth-generation devices based on e-liquids containing nicotine salts that promise a smoother vaping experience than freebase nicotine. However, the toxicological effects of nicotine salts are still largely unknown, and the chemical diversity of e-liquids limits the comparison between different studies to determine the contribution of each compound to the cytotoxicity of EC aerosols. Therefore, the aim of this study was to evaluate the toxicological profile of controlled composition e-liquid aerosols to accurately determine the effects of each ingredient based on exposure at the air-liquid interface. Methods Human lung epithelial cells (A549) were exposed to undiluted aerosols of controlled composition e-liquids containing various ratios of propylene glycol (PG)/vegetable glycerin (VG) solvents, freebase nicotine, organic acids, nicotine salts, and flavoured commercial e-liquids. Exposure of 20 puffs was performed at the air-liquid interface following a standard vaping regimen. Toxicological outcomes, including cytotoxicity, inflammation, and oxidative stress, were assessed 24 h after exposure. Results PG/VG aerosols elicited a strong cytotoxic response characterised by a 50% decrease in cell viability and a 200% increase in lactate dehydrogenase (LDH) production, but had no effects on inflammation and oxidative stress. These effects occurred only at a ratio of 70/30 PG/VG, suggesting that PG is the major contributor to aerosol cytotoxicity. Both freebase nicotine and organic acids had no greater effect on cell viability and LDH release than at a 70/30 PG/VG ratio, but significantly increased inflammation and oxidative stress. Interestingly, the protonated form of nicotine in salt showed a stronger proinflammatory effect than the freebase nicotine form, while benzoic acid-based nicotine salts also induced significant oxidative stress. Flavoured commercial e-liquids was found to be cytotoxic at a threshold dose of ≈ 330 µg/cm². Conclusion Our results showed that aerosols of e-liquids consisting only of PG/VG solvents can cause severe cytotoxicity depending on the concentration of PG, while nicotine salts elicit a stronger pro-inflammatory response than freebase nicotine. Overall, aerosols from fourth-generation devices can cause different toxicological effects, the nature of which depends on the chemical composition of the e-liquid. |
| first_indexed | 2024-03-07T14:44:48Z |
| format | Article |
| id | doaj.art-7d92739508ab4f5880127d2890bf7848 |
| institution | Directory Open Access Journal |
| issn | 1465-993X |
| language | English |
| last_indexed | 2024-03-07T14:44:48Z |
| publishDate | 2024-02-01 |
| publisher | BMC |
| record_format | Article |
| series | Respiratory Research |
| spelling | doaj.art-7d92739508ab4f5880127d2890bf78482024-03-05T20:02:42ZengBMCRespiratory Research1465-993X2024-02-0125111810.1186/s12931-024-02697-2In vitro toxicological evaluation of aerosols generated by a 4th generation vaping device using nicotine salts in an air-liquid interface systemClément Mercier0Jérémie Pourchez1Lara Leclerc2Valérie Forest3Mines Saint-Etienne, Université Jean Monnet, INSERM, U1059 Sainbiose, Centre CISMines Saint-Etienne, Université Jean Monnet, INSERM, U1059 Sainbiose, Centre CISMines Saint-Etienne, Université Jean Monnet, INSERM, U1059 Sainbiose, Centre CISMines Saint-Etienne, Université Jean Monnet, INSERM, U1059 Sainbiose, Centre CISAbstract Background Electronic cigarettes (EC) have gained popularity, especially among young people, with the introduction of fourth-generation devices based on e-liquids containing nicotine salts that promise a smoother vaping experience than freebase nicotine. However, the toxicological effects of nicotine salts are still largely unknown, and the chemical diversity of e-liquids limits the comparison between different studies to determine the contribution of each compound to the cytotoxicity of EC aerosols. Therefore, the aim of this study was to evaluate the toxicological profile of controlled composition e-liquid aerosols to accurately determine the effects of each ingredient based on exposure at the air-liquid interface. Methods Human lung epithelial cells (A549) were exposed to undiluted aerosols of controlled composition e-liquids containing various ratios of propylene glycol (PG)/vegetable glycerin (VG) solvents, freebase nicotine, organic acids, nicotine salts, and flavoured commercial e-liquids. Exposure of 20 puffs was performed at the air-liquid interface following a standard vaping regimen. Toxicological outcomes, including cytotoxicity, inflammation, and oxidative stress, were assessed 24 h after exposure. Results PG/VG aerosols elicited a strong cytotoxic response characterised by a 50% decrease in cell viability and a 200% increase in lactate dehydrogenase (LDH) production, but had no effects on inflammation and oxidative stress. These effects occurred only at a ratio of 70/30 PG/VG, suggesting that PG is the major contributor to aerosol cytotoxicity. Both freebase nicotine and organic acids had no greater effect on cell viability and LDH release than at a 70/30 PG/VG ratio, but significantly increased inflammation and oxidative stress. Interestingly, the protonated form of nicotine in salt showed a stronger proinflammatory effect than the freebase nicotine form, while benzoic acid-based nicotine salts also induced significant oxidative stress. Flavoured commercial e-liquids was found to be cytotoxic at a threshold dose of ≈ 330 µg/cm². Conclusion Our results showed that aerosols of e-liquids consisting only of PG/VG solvents can cause severe cytotoxicity depending on the concentration of PG, while nicotine salts elicit a stronger pro-inflammatory response than freebase nicotine. Overall, aerosols from fourth-generation devices can cause different toxicological effects, the nature of which depends on the chemical composition of the e-liquid.https://doi.org/10.1186/s12931-024-02697-2Electronic cigaretteToxicologyAerosolAir-liquid interface4th generation deviceNicotine salts |
| spellingShingle | Clément Mercier Jérémie Pourchez Lara Leclerc Valérie Forest In vitro toxicological evaluation of aerosols generated by a 4th generation vaping device using nicotine salts in an air-liquid interface system Respiratory Research Electronic cigarette Toxicology Aerosol Air-liquid interface 4th generation device Nicotine salts |
| title | In vitro toxicological evaluation of aerosols generated by a 4th generation vaping device using nicotine salts in an air-liquid interface system |
| title_full | In vitro toxicological evaluation of aerosols generated by a 4th generation vaping device using nicotine salts in an air-liquid interface system |
| title_fullStr | In vitro toxicological evaluation of aerosols generated by a 4th generation vaping device using nicotine salts in an air-liquid interface system |
| title_full_unstemmed | In vitro toxicological evaluation of aerosols generated by a 4th generation vaping device using nicotine salts in an air-liquid interface system |
| title_short | In vitro toxicological evaluation of aerosols generated by a 4th generation vaping device using nicotine salts in an air-liquid interface system |
| title_sort | in vitro toxicological evaluation of aerosols generated by a 4th generation vaping device using nicotine salts in an air liquid interface system |
| topic | Electronic cigarette Toxicology Aerosol Air-liquid interface 4th generation device Nicotine salts |
| url | https://doi.org/10.1186/s12931-024-02697-2 |
| work_keys_str_mv | AT clementmercier invitrotoxicologicalevaluationofaerosolsgeneratedbya4thgenerationvapingdeviceusingnicotinesaltsinanairliquidinterfacesystem AT jeremiepourchez invitrotoxicologicalevaluationofaerosolsgeneratedbya4thgenerationvapingdeviceusingnicotinesaltsinanairliquidinterfacesystem AT laraleclerc invitrotoxicologicalevaluationofaerosolsgeneratedbya4thgenerationvapingdeviceusingnicotinesaltsinanairliquidinterfacesystem AT valerieforest invitrotoxicologicalevaluationofaerosolsgeneratedbya4thgenerationvapingdeviceusingnicotinesaltsinanairliquidinterfacesystem |