Author's response to: "Harmful effects form one puff of shisha-pen vapor: methodological and interpretational problems in the risk assessment analysis"

We thank Dr. Farsalinos and Dr. Baeyens for their comments in their letter to the editor on our publication: “Potential harmful health effects of inhaling nicotine-free shisha-pen vapor: a chemical risk assessment of the main components propylene glycol and glycerol” [1]. Apparently some issues discussed in our publication were not sufficiently clear and we thank the editor of Tobacco Induced Diseases for the opportunity to respond to these comments and clarify the issues raised. The comments made by Dr. Farsalinos and Dr. Baeyens focus on four specific issues. Their main concern however, is about the applicability of our proposal to use the Margin of Exposure (MOE) approach for risk assessment of exposure via shisha-pens or electronic cigarettes (e-cigarettes). Therefore, we would like to elaborate first on the application of this approach as a method of risk assessment for exposure to chemicals via smoking and vaping and why we are of the opinion that, at present, this is the best method for the present exposure scenario. The exposure pattern in smoking or vaping is rather complex. E-cigarettes or shisha-pens may be used during one or more vaping sessions per day and a session consists of a variable number of puffs. Thus during a day, exposure is intermittent in two ways, i.e., time intervals exist between sessions and between puffs within each session. Since exposure occurs only when a puff is taken, the daily exposure consists of multiple peak exposures with irregular time intervals in between. The exposure assessment is further complicated by the large variation in the use of e-cigarettes. Based on a market survey of the use of e-cigarettes in The Netherlands, it has been estimated that the number of puffs during a day may be up to 500 (or even larger in individual cases) with a total duration (i.e., total sum of session duration) of 4 h per day. The question then raised is how risks can be estimated from such a complex exposure scenario. The available human limit values for respiratory exposures are not suitable. Occupational exposure limits (OELs) are not applicable to the general population and are generally meant for 8-h exposures while limit values for the general population (such as Air Quality Guidelines as published by the WHO) are generally derived for continuous exposure, i.e., 24 h per day for 7 days per week. The exposure scenarios for which these limit values are derived do not match the exposure pattern for vaping. Hence, the question then is how to proceed if one wants to assess the health risks from the use of ecigarettes or shisha-pens? We believe that the best option forward is the application of the Margin of Exposure (MOE) analysis. This approach is commonly used within different risk assessment frameworks and has been used before in a risk assessment for exposure to 1,3-butadiene through smoking [2]. The MOE approach has also been proposed in risk assessment of smoking by others (e.g., [3, 4]). A manuscript describing the application of the MOE within risk assessment of smoking or vaping in more detail is in preparation. An MOE is the ratio of a reference point (the PoD), often taken from an animal study and corresponding to an exposure that causes a low but measurable response, and the exposure estimate in humans, taking into account differences in vaping behaviour (adapted from [5]). The MOE approach starts with the choice of an appropriate PoD that is derived from an exposure scenario that closely resembles the exposure scenario under evaluation and preferably is based on human data. * Correspondence: [email protected] National Institute for Public Health and the Environment, Bilthoven, The Netherlands