Methodological Approaches for Risk Assessment of Tobacco and Related Products
Abstract
:1. Introduction
2. Methods for Quantifying Risk
2.1. Evaluation Frameworks
2.2. Risk Assessment Based on Individual Components
2.2.1. Threshold of Toxicological Concern
2.2.2. Hazard Quotient and Hazard Index
2.2.3. Margin of Exposure Approach
2.2.4. Comparison of the HI/HQ Approach and the Margin of Exposure Approach
2.2.5. Relative Potency Approaches
2.3. Risk Assessment of the Product as a Whole
2.4. Possibilities and Limitations of Risk Assessment Methods
3. Challenges to Quantifying Risk
3.1. Product Variation
3.2. User-Related Factors
3.3. Complex Mixture of Components in the Emission
4. Discussion
4.1. Overview and Applications
4.2. Risk Characterization
4.3. Risks at Population Level
4.4. Implications for Regulation
4.5. Recommendations
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
- WHO. Tobacco. 2019. Available online: https://www.who.int/news-room/fact-sheets/detail/tobacco (accessed on 4 March 2020).
- Sinha, D.N.; Palipudi, K.M.; Gupta, P.C.; Singhal, S.; Ramasundarahettige, C.; Jha, P.; Indrayan, A.; Asma, S.; Vendhan, G. Smokeless tobacco use: A meta-analysis of risk and attributable mortality estimates for India. Indian J. Cancer 2014, 51 (Suppl. S1), S73–S77. [Google Scholar] [CrossRef] [PubMed]
- Slob, W.; Soeteman-Hernández, L.G.; Bil, W.; Staal, Y.C.M.; Stephens, W.E.; Talhout, R. A method for comparing the impact on carcinogenicity of tobacco products: A case study on heated tobacco versus cigarettes. Risk Anal. 2020, 40, 1355–1366. [Google Scholar] [CrossRef] [PubMed]
- Fowles, J.; Dybing, E. Application of toxicological risk assessment principles to the chemical constituents of cigarette smoke. Tob. Control 2003, 12, 424–430. [Google Scholar] [CrossRef] [PubMed]
- Ashley, D.L.; Burns, D.; Djordjevic, M.; Dybing, E.; Gray, N.; Hammond, S.K.; Henningfield, J.; Jarvis, M.; Reddy, K.S.; Robertson, C.; et al. The scientific Basis Of Tobacco Product Regulation; World Health Organization Technical Report Series; World Health Organization: Geneva, Switzerland, 2008; pp. 1–277. [Google Scholar]
- Burns, D.M.; Dybing, E.; Gray, N.; Hecht, S.; Anderson, C.; Sanner, T.; O’Connor, R.; Djordjevic, M.; Dresler, C.; Hainaut, P.; et al. Mandated lowering of toxicants in cigarette smoke: A description of the World Health Organization TobReg proposal. Tob. Control 2008, 17, 132–141. [Google Scholar] [CrossRef]
- WHO. Work in Progress in Relation to Articles 9 and 10 of the WHO FCTC; World Health Organization: Geneva, Switzerland, 2014; Available online: http://apps.who.int/gb/fctc/PDF/cop6/FCTC_COP6_14-en.pdf (accessed on 15 April 2022).
- U.S. Department of Health and Human Services; CDC. Smoking Cessation: A Report of the Surgeon General. 2020. Available online: https://www.hhs.gov/sites/default/files/2020-cessation-sgr-full-report.pdf (accessed on 15 April 2022).
- Staal, Y.C.M.; Havermans, A.; van Nierop, L.; Visser, W.; Wijnhoven, S.; Bil, W.; Talhout, R. Conceptual model for the evaluation of attractiveness, addictiveness and toxicity of tobacco and related products: The example of JUUL e-cigarettes. Regul Toxicol Pharmacol. 2021, 127, 105077. [Google Scholar] [CrossRef]
- Berman, M.L.; El-Sabawi, T.; Shields, P.G. Risk Assessment for Tobacco Regulation. Tob. Regul. Sci. 2019, 5, 36–49. [Google Scholar] [CrossRef]
- van Amsterdam, J.; Nutt, D.; Phillips, L.; van den Brink, W. European rating of drug harms. J. Psychopharmacol. 2015, 29, 655–660. [Google Scholar] [CrossRef]
- van Amsterdam, J.; Opperhuizen, A.; Koeter, M.; van den Brink, W. Ranking the harm of alcohol, tobacco and illicit drugs for the individual and the population. Eur. Addict. Res. 2010, 16, 202–207. [Google Scholar] [CrossRef]
- WHO. The Scientific Basis of Tobacco Product Regulation; World Health Organization: Geneva, Switzerland, 2007; Volume 945. [Google Scholar]
- Wagner, K.A.; Flora, J.W.; Melvin, M.S.; Avery, K.C.; Ballentine, R.M.; Brown, A.P.; McKinney, W.J. An evaluation of electronic cigarette formulations and aerosols for harmful and potentially harmful constituents (HPHCs) typically derived from combustion. Regul Toxicol Pharmacol 2018, 95, 153–160. [Google Scholar] [CrossRef]
- Margham, J.; McAdam, K.; Cunningham, A.; Porter, A.; Fiebelkorn, S.; Mariner, D.; Digard, H.; Proctor, C. The Chemical Complexity of e-Cigarette Aerosols Compared With the Smoke From a Tobacco Burning Cigarette. Front. Chem. 2021, 9, 743060. [Google Scholar] [CrossRef]
- Leeman, W.R.; Krul, L.; Houben, G.F. Complex mixtures: Relevance of combined exposure to substances at low dose levels. Food Chem. Toxicol. 2013, 58, 141–148. [Google Scholar] [CrossRef] [PubMed]
- EFSA Scientific Committee. Scientific Opinion on Exploring options for providing advice about possible human health risks based on the concept of Threshold of Toxicological Concern (TTC). EFSA J. 2012, 10, 2750. [Google Scholar] [CrossRef]
- Kawamoto, T.; Fuchs, A.; Fautz, R.; Morita, O. Threshold of Toxicological Concern (TTC) for Botanical Extracts (Botanical-TTC) derived from a meta-analysis of repeated-dose toxicity studies. Toxicol. Lett. 2019, 316, 1–9. [Google Scholar] [CrossRef]
- Rietjens, I.; Cohen, S.M.; Eisenbrand, G.; Fukushima, S.; Gooderham, N.J.; Guengerich, F.P.; Hecht, S.S.; Rosol, T.J.; Davidsen, J.M.; Harman, C.L.; et al. FEMA GRAS assessment of natural flavor complexes: Cinnamomum and Myroxylon-derived flavoring ingredients. Food Chem Toxicol 2020, 135, 110949. [Google Scholar] [CrossRef] [PubMed]
- Tluczkiewicz, I.; Kuhne, R.; Ebert, R.U.; Batke, M.; Schuurmann, G.; Mangelsdorf, I.; Escher, S.E. Inhalation TTC values: A new integrative grouping approach considering structural, toxicological and mechanistic features. Regul. Toxicol. Pharm. 2016, 78, 8–23. [Google Scholar] [CrossRef] [PubMed]
- Schuurmann, G.; Ebert, R.U.; Tluczkiewicz, I.; Escher, S.E.; Kuhne, R. Inhalation threshold of toxicological concern (TTC)—Structural alerts discriminate high from low repeated-dose inhalation toxicity. Environ. Int. 2016, 88, 123–132. [Google Scholar] [CrossRef]
- Talhout, R.; Schulz, T.; Florek, E.; van Benthem, J.; Wester, P.; Opperhuizen, A. Hazardous compounds in tobacco smoke. Int. J. Environ. Res. Public Health 2011, 8, 613–628. [Google Scholar] [CrossRef]
- Bos, P.M.J.; Soeteman-Hernández, L.G.; Talhout, R. Risk assessment of components in tobacco smoke and e-cigarette aerosols: A pragmatic choice of dose metrics. Inhal. Toxicol. 2021, 33, 81–95. [Google Scholar] [CrossRef]
- Sarigiannis, D.A.; Hansen, U. Considering the cumulative risk of mixtures of chemicals—A challenge for policy makers. Environ. Health 2012, 11 (Suppl. S1), S18. [Google Scholar] [CrossRef]
- Wilkinson, C.F.; Christoph, G.R.; Julien, E.; Kelley, J.M.; Kronenberg, J.; McCarthy, J.; Reiss, R. Assessing the risks of exposures to multiple chemicals with a common mechanism of toxicity: How to cumulate? Regul. Toxicol. Pharmacol. 2000, 31, 30–43. [Google Scholar] [CrossRef]
- Visser, W.F.; Klerx, W.N.; Cremers, H.; Ramlal, R.; Schwillens, P.L.; Talhout, R. The Health Risks of Electronic Cigarette Use to Bystanders. Int. J. Environ. Res. Public Health 2019, 16, 1525. [Google Scholar] [CrossRef] [PubMed]
- Cunningham, F.H.; Fiebelkorn, S.; Johnson, M.; Meredith, C. A novel application of the Margin of Exposure approach: Segregation of tobacco smoke toxicants. Food Chem. Toxicol. 2011, 49, 2921–2933. [Google Scholar] [CrossRef] [PubMed]
- Soeteman-Hernández, L.G.; Bos, P.M.; Talhout, R. Tobacco smoke-related health effects induced by 1,3-butadiene and strategies for risk reduction. Toxicol. Sci. 2013, 136, 566–580. [Google Scholar] [CrossRef]
- Safe, S.H. Polychlorinated biphenyls (PCBs): Environmental impact, biochemical and toxic responses, and implications for risk assessment. Crit. Rev. Toxicol. 1994, 24, 87–149. [Google Scholar] [CrossRef] [PubMed]
- Reeves, W.R.; Barhoumi, R.; Burghardt, R.C.; Lemke, S.L.; Mayura, K.; McDonald, T.J.; Phillips, T.D.; Donnelly, K.C. Evaluation of methods for predicting the toxicity of polycyclic aromatic hydrocarbon mixtures. Environ. Sci. Technol. 2001, 35, 1630–1636. [Google Scholar] [CrossRef] [PubMed]
- Boon, P.E.; Van der Voet, H.; Van Raaij, M.T.; Van Klaveren, J.D. Cumulative risk assessment of the exposure to organophosphorus and carbamate insecticides in the Dutch diet. Food Chem. Toxicol. 2008, 46, 3090–3098. [Google Scholar] [CrossRef]
- Bil, W.; Zeilmaker, M.; Fragki, S.; Lijzen, J.; Verbruggen, E.; Bokkers, B. Risk Assessment of Per- and Polyfluoroalkyl Substance Mixtures: A Relative Potency Factor Approach. Environ. Toxicol. Chem. 2021, 40, 859–870. [Google Scholar] [CrossRef]
- Stephens, W.E. Comparing the cancer potencies of emissions from vapourised nicotine products including e-cigarettes with those of tobacco smoke. Tob. Control 2017, 27, 10–17. [Google Scholar] [CrossRef]
- Staal, Y.C.M.; Bil, W.; Bokkers, B.; Soeteman-Hernández, L.G.; Stephens, W.E.; Talhout, R. Challenges in predicting the change in the cumulative exposure of new tobacco and related products based on emissions and toxicity dose-response data. 2022; accepted for publication in International Journal of Environmental Research and Public Health. [Google Scholar]
- Owusu, D.; Huang, J.; Weaver, S.R.; Pechacek, T.F.; Ashley, D.L.; Nayak, P.; Eriksen, M.P. Patterns and trends of dual use of e-cigarettes and cigarettes among U.S. adults, 2015–2018. Prev. Med. Rep. 2019, 16, 101009. [Google Scholar] [CrossRef]
- Havermans, A.; Krüsemann, E.J.Z.; Pennings, J.; de Graaf, K.; Boesveldt, S.; Talhout, R. Nearly 20,000 e-liquids and 250 unique flavour descriptions: An overview of the Dutch market based on information from manufacturers. Tob. Control 2021, 30, 57–62. [Google Scholar] [CrossRef] [Green Version]
- Di Consiglio, E.; Pistollato, F.; Mendoza-De Gyves, E.; Bal-Price, A.; Testai, E. Integrating biokinetics and in vitro studies to evaluate developmental neurotoxicity induced by chlorpyrifos in human iPSC-derived neural stem cells undergoing differentiation towards neuronal and glial cells. Reprod. Toxicol. 2020, 98, 174–188. [Google Scholar] [CrossRef] [PubMed]
- Meldrum, K.; Evans, S.J.; Vogel, U.; Tran, L.; Doak, S.H.; Clift, M.J.D. The influence of exposure approaches to in vitro lung epithelial barrier models to assess engineered nanomaterial hazard. Nanotoxicology 2022, 16, 114–134. [Google Scholar] [CrossRef] [PubMed]
- Hayashi, Y. Designing in vitro assay systems for hazard characterization. basic strategies and related technical issues. Exp. Toxicol. Pathol. 2005, 57 (Suppl. S1), 227–232. [Google Scholar] [CrossRef] [PubMed]
- Lauterstein, D.; Savidge, M.; Chen, Y.; Weil, R.; Yeager, R.P. Nonanimal toxicology testing approaches for traditional and deemed tobacco products in a complex regulatory environment: Limitations, possibilities, and future directions. Toxicol. Vitr. 2020, 62, 104684. [Google Scholar] [CrossRef] [PubMed]
- Mallock, N.; Pieper, E.; Hutzler, C.; Henkler-Stephani, F.; Luch, A. Heated Tobacco Products: A Review of Current Knowledge and Initial Assessments. Front. Public Health 2019, 7, 287. [Google Scholar] [CrossRef]
- Bopp, S.K.; Barouki, R.; Brack, W.; Dalla Costa, S.; Dorne, J.C.M.; Drakvik, P.E.; Faust, M.; Karjalainen, T.K.; Kephalopoulos, S.; van Klaveren, J.; et al. Current EU research activities on combined exposure to multiple chemicals. Environ. Int. 2018, 120, 544–562. [Google Scholar] [CrossRef]
- EFSA Scientific Committee. Guidance on harmonised methodologies for human health, animal health and ecotoxicological risk assessment of combined exposure to multiple chemicals. EFSA J. 2019, 17, 5634. [Google Scholar] [CrossRef]
- Thompson, C.M.; Bhat, V.S.; Brorby, G.P.; Haws, L.C. Development of updated RfD and RfC values for medium carbon range aromatic and aliphatic total petroleum hydrocarbon fractions. J. Air Waste Manag. Assoc. 2021, 71, 1555–1567. [Google Scholar] [CrossRef]
- Zavala, J.; Freedman, A.N.; Szilagyi, J.T.; Jaspers, I.; Wambaugh, J.F.; Higuchi, M.; Rager, J.E. New Approach Methods to Evaluate Health Risks of Air Pollutants: Critical Design Considerations for In Vitro Exposure Testing. Int. J. Environ. Res. Public Health 2020, 17, 2124. [Google Scholar] [CrossRef]
- Kane, D.B.; Asgharian, B.; Price, O.T.; Rostami, A.; Oldham, M.J. Effect of smoking parameters on the particle size distribution and predicted airway deposition of mainstream cigarette smoke. Inhal. Toxicol. 2010, 22, 199–209. [Google Scholar] [CrossRef]
- Sosnowski, T.R.; Kramek-Romanowska, K. Predicted Deposition of E-Cigarette Aerosol in the Human Lungs. J. Aerosol Med. Pulm. Drug Deliv. 2016, 29, 299–309. [Google Scholar] [CrossRef] [PubMed]
- Apelberg, B.J.; Feirman, S.P.; Salazar, E.; Corey, C.G.; Ambrose, B.K.; Paredes, A.; Richman, E.; Verzi, S.J.; Vugrin, E.D.; Brodsky, N.S.; et al. Potential Public Health Effects of Reducing Nicotine Levels in Cigarettes in the United States. N. Engl. J. Med. 2018, 378, 1725–1733. [Google Scholar] [CrossRef] [PubMed]
- Meek, M.E.; Boobis, A.R.; Crofton, K.M.; Heinemeyer, G.; Raaij, M.V.; Vickers, C. Risk assessment of combined exposure to multiple chemicals: A WHO/IPCS framework. Regul. Toxicol. Pharmacol. 2011, 60 (Suppl. S1), S1–S14. [Google Scholar] [CrossRef] [Green Version]
Potential Application for TRPs | Main Limitations | Main Advantages | |
---|---|---|---|
Evaluation frameworks (with or without scoring) | Qualitative health risk assessment based on scores, can be used for setting priorities | Most subjective method No quantification of risks | Requires limited data; more data will improve outcomes |
Threshold of toxicological concern (TTC) | Identification of components for further assessment/testing | Cannot assess risk of complete product. No quantification of risks | Identification of components of no concern |
Hazard quotient (HQ)/Hazard index (HI) | Health risk assessment based on available data Health risk assessment of groups of components sharing the same toxicity endpoint | High data requirement. Only for groups with reference value based on similar toxicity endpoint Assessment factors may be based on non-scientific considerations | Considers target organ in the evaluation |
Margin of exposure approach (MoE) | Identification of risks of components of concern Comparison between products on risks from individual components | High data requirement Cannot sum risks of different substances | Identification of individual components of (potential) concern |
Relative potency approaches | Health risk assessment based on total risk of groups of components sharing the same toxicological endpoint Comparison between products based on groups of components | High data requirement for all components within a group. Components should share the same toxicological endpoint | Allows comparison of risks between products for groups of components |
In vivo or in vitro studies with whole emission exposure | Hazard assessment based on dose–response data of mixture as a whole | Extensive testing required and extrapolation of exposure and results to humans Only information on one composition | Does not require data on emissions or hazard of individual components as the model is exposed to the emission as a whole Includes agonistic and antagonistic effects of all components |
Factor | Effect on | |
---|---|---|
Product-related | Settings of the device | Identity and quantity of components in emission, particle size distribution |
Product-related | Product itself (such as brand) | Identity and quantity of components in emission, particle size distribution |
User-related | Topography | Identity and quantity of components in the emission, user exposure |
User-related | Number of items consumed per day | Quantity inhaled of each component, user exposure |
User-related | Breathing volume | Quantity of air inhaled with a puff dilutes the emission and therefore determines the concentrations inhaled |
Complex mixtures | Burning and degradation | Identity and quantity of components in emission |
Complex mixtures | Emissions from other sources, such as the device | Identity and quantity of components in emission |
Complex mixtures | Aerosol aging, humidification in the airways | Particle size distribution |
Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations. |
© 2022 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
Share and Cite
Staal, Y.C.M.; Bos, P.M.J.; Talhout, R. Methodological Approaches for Risk Assessment of Tobacco and Related Products. Toxics 2022, 10, 491. https://doi.org/10.3390/toxics10090491
Staal YCM, Bos PMJ, Talhout R. Methodological Approaches for Risk Assessment of Tobacco and Related Products. Toxics. 2022; 10(9):491. https://doi.org/10.3390/toxics10090491
Chicago/Turabian StyleStaal, Yvonne C. M., Peter M. J. Bos, and Reinskje Talhout. 2022. "Methodological Approaches for Risk Assessment of Tobacco and Related Products" Toxics 10, no. 9: 491. https://doi.org/10.3390/toxics10090491