Insights into the Health Effects of Acrolein and Crotonaldehyde in Russian Smokers Switching from Regular Cigarettes to Heated Tobacco Products

The effects of acrolein and crotonaldehyde on the health of Russian smokers upon switching to heated tobacco product use were analyzed in a five-day randomized clinical trial. The findings suggest that heated tobacco products significantly reduce exposure to these toxicants, with the adverse effects becoming less pronounced in just one day and comparable to complete cessation of smoking. The dynamics of nicotine intake and metabolism in the smokers who switched to heated tobacco products remained stable throughout the study and was similar to that in the group of regular cigarette smokers.

Therefore, our study, which has been performed for the first time among the Russian population, shows that smokers switching to heated tobacco products are less exposed to harmful chemicals like acrolein and crotonaldehyde and thus may be protected against some of the negative health effects often associated with regular cigarettes.

1. IARC Working Group on the Evaluation of Carcinogenic Risks to Humans. Acrolein // IARC Monographs on the Evaluation of Carcinogenic Risks to Humans. V. 63: Dry cleaning, some chlorinated solvents and other industrial chemicals. Lyon: Int. Agency Res. Cancer, 1995. P. 337–372.

2. IARC Working Group on the Evaluation of Carcinogenic Risks to Humans. Crotonaldehyde // IARC Monographs on the Evaluation of Carcinogenic Risks to Humans. V. 63: Dry cleaning, some chlorinated solvents and other industrial chemicals. Lyon: Int. Agency Res. Cancer, 1995. P. 373–391.

3. Park S.L., Carmella S.G., Chen M., Patel Y., Stram D.O., Haiman C.A., Le Marchand L., Hecht S.S. Mercapturic acids derived from the toxicants acrolein and crotonaldehyde in the urine of cigarette smokers from five ethnic groups with differing risks for lung cancer // PLoS ONE. 2015. V. 10, No 6. Art. e0124841. doi: 10.1371/journal.pone.0124841.

4. Kensler C.J., Battista S.P. Components of cigarette smoke with ciliary-depressant activity. Their selective removal by filters containing activated charcoal granule // N. Engl. J. Med. 1963. V. 269. P. 1161–1166. doi: 10.1056/NEJM196311282692202.

5. Alwis K.U., de Castro B.R., Morrow J.C., Blount B.C. Acrolein exposure in U.S. tobacco smokers and non-tobacco users: NHANES 2005–2006 // Environ. Health Perspect. 2015. V. 123, No 12. P. 1302–1308. doi: 10.1289/ehp.1409251.

6. Bagchi P., Geldner N., de Castro B.R., De Jesús V.R., Park S.K., Blount B.C. Crotonaldehyde exposure in U.S. tobacco smokers and nonsmokers: NHANES 2005–2006 and 2011–2012 // Environ. Res. 2018. V. 163. P. 1–9. doi: 10.1016/j.envres.2018.01.033.

7. Levin E.D., Rose J.E., Behm F., Caskey N.H. The effects of smoking-related sensory cues on psychological stress // Pharmacol. Biochem. Behav. 1991. V. 39, No 2. P. 265–268. doi: 10.1016/0091-3057(91)90177-4.

8. Schaller J.-P., Keller D., Poget L., Pratte P., Kaelin E., McHugh D., Cudazzo G., Smart D., Tricker A.R., Gautier L., Yerly M., Reis Pires R., Le Bouhellec S., Ghosh D., Hofer I., Garcia E., Vanscheeuwijck P., Maeder S. Evaluation of the Tobacco Heating System 2.2. Part 2: Chemical composition, genotoxicity, cytotoxicity, and physical properties of the aerosol // Regul. Toxicol. Pharmacol. 2016. V. 81, Suppl. 2. P. S27–S47. doi: 10.1016/j.yrtph.2016.10.001.

9. Wong E.T., Kogel U., Veljkovic E., Martin F., Xiang Y., Boue S., Vuillaume G., Leroy P., Guedj E., Rodrigo G., Ivanov N.V., Hoeng J., Peitsch M.C., Vanscheeuwijck P. Evaluation of the Tobacco Heating System 2.2. Part 4: 90-day OECD 413 rat inhalation study with systems toxicology endpoints demonstrates reduced exposure effects compared with cigarette smoke // Regul. Toxicol. Pharmacol. 2016. V. 81, Suppl. 2. P. S59–S81. doi: 10.1016/j.yrtph.2016.10.015.

10. Haziza C., de La Bourdonnaye G., Skiada D., Ancerewicz J., Baker G., Picavet P., Lüdicke F. Evaluation of the Tobacco Heating System 2.2. Part 8: 5-Day randomized reduced exposure clinical study in Poland // Regul. Toxicol. Pharmacol. 2016. V. 81, Suppl. 2. P. S139–S150. doi: 10.1016/j.yrtph.2016.11.003.

11. Stevens J.F., Maier C.S. Acrolein: Sources, metabolism, and biomolecular interactions relevant to human health and disease // Mol. Nutr. Food Res. 2008. V. 52, No 1. P. 7–25. doi: 10.1002/mnfr.200700412.

12. Pan J., Chung F.-L. Formation of cyclic deoxyguanosine adducts from ω-3 and ω-6 polyunsaturated fatty acids under oxidative conditions // Chem. Res. Toxicol. 2002. V. 15, No 3. P. 367–372. doi: 10.1021/tx010136q.

13. Neurath G.B., Dünger M., Orth D., Pein F.G. Trans-3’-hydroxycotinine as a main metabolite in urine of smokers // Int. Arch. Occup. Environ. Health. 1987. V. 59, No 2. P. 199–201. doi: 10.1007/BF00378497.

14. Lopukhov L.V., Laikov A.V., Romanova V.A., Gatina D.Z., Lopukhov V.L., Abdulkhakov S.R., Zaitseva T.A., Medvedeva S.N., Gnuchikh E.V., Salafutdinov I.I., Grigoryeva T.V. LC-MS method development for simultaneous determination of trans-3′-hydroxycotinine and three mercapturic acids in urine // BioNanoScience. 2018. V. 8, No 3. P. 924–929. doi: 10.1007/s12668-018-0528-1.