Risk assessment methods for tobacco and nicotine products

Risk assessment of tobacco and nicotine products is challenging due to their complex nature, composition and use. In addition to product specific risk assessment, RIVM has developed a method to compare the cumulative exposure between various tobacco and nicotine products. This method gives an indication of the difference in exposure to hazardous compounds in the emission. RIVM also developed an evaluation framework that gives insight into the determinants of health risk of tobacco and nicotine products use and can be used for initial assessment of health impact and to define further focus of research. Finally, we have summarised risk assessment methods and pros and cons for their application in toxicological risk assessment of tobacco and nicotine products.

Toxicological assessment of specific products

When new tobacco or nicotine products enter the market, insight into their toxicological effects is needed to estimate the impact on the user’s health. This toxicological assessment provides information for legislation but also the general public. Several tobacco and nicotine products have been assessed, such as e-cigarettes, heated tobacco products (specifically the IQOS) and nicotine pouches. 

Toxicological research on the effects of specific compounds in the product or emission

In addition to toxicological assessment of a complete product, RIVM evaluates information on the toxicity of individual compounds in the product or in the emission of tobacco and nicotine products. For example, RIVM reviewed toxicological effects of 23 flavourings in e-cigarettes. The use of seven of these flavourings was found to be potentially harmful to human health. These findings supported the development of a restricted list of allowed flavouring ingredients that will only enable the production of e-liquids with a tobacco flavour.

As the availability of information on the toxicological effects of ingredients and emissions is limited, RIVM also performs in vitro toxicological research focused on the effects of specific compounds in tobacco and nicotine products. In this research, we use airway epithelium cells, cultured at the air-liquid interface and expose the cells to emissions from tobacco and nicotine products via the air. We have explored the use of different cell models, cultured at the air-liquid-interface for exposure to airborne compounds and developed a co-culture model of lung epithelium cells with macrophages. In addition, we have combined such a cell model with neuronal cultures to assess neuromodulatory effects of inhaled compounds.

Exposure of bystanders

When people smoke in public outdoor spaces, bystanders can be exposed to cigarette smoke, also called second hand or passive smoking. The RIVM method measured quantities of nicotine, 3-ethenylpyridine and particulate matter 2.5 to give an indication of bystander exposure to cigarette smoke in public outdoor spaces. Quantities of these substances were higher when smokers were present, compared to situations in which smokers were absent.  In some locations, nicotine remained detectable in the absence of smoking, suggesting that nicotine remains airborne even after smokers have left the location. In a study on health risks of e-cigarettes to bystanders, RIVM found that bystanders may experience mild irritation of the throat, nose and eyes. Furthermore, if nicotine-containing e-liquids are used, bystanders may experience palpitations and increased blood pressure as a result of exposure to nicotine