Comparative risk assessment of tobacco smoke constituents using the margin of exposure approach: the neglected contribution of nicotine

Abstract

Nicotine was not included in previous efforts to identify the most important toxicants of tobacco smoke. A health risk assessment of nicotine for smokers of cigarettes was conducted using the margin of exposure (MOE) approach and results were compared to literature MOEs of various other tobacco toxicants. The MOE is defined as ratio between toxicological threshold (benchmark dose) and estimated human intake. Dose-response modelling of human and animal data was used to derive the benchmark dose. The MOE was calculated using probabilistic Monte Carlo simulations for daily cigarette smokers. Benchmark dose values ranged from 0.004 mg/kg bodyweight for symptoms of intoxication in children to 3 mg/kg bodyweight for mortality in animals; MOEs ranged from below 1 up to 7.6 indicating a considerable consumer risk. The dimension of the MOEs is similar to those of other tobacco toxicants with high concerns relating to adverse health effects such as acrolein or formaldehyde. Owing to the lack of toxicological data in particular relating to cancer, long term animal testing studies for nicotine are urgently necessary. There is immediate need of action concerning the risk of nicotine also with regard to electronic cigarettes and smokeless tobacco.

Trace Metals Derived from Electronic Cigarette (ECIG) Generated Aerosol: Potential Problem of ECIG Devices That Contain Nickel

“…Smoking one pack of cigarettes per day can garner up to 10 and 3% of the estimated maximum allowance of Cd and As inhalation, respectively. While these values appear low as compared to maximum allowable inhalation based on OSHA's PEL, a number of studies (Cunningham et al, 2011; Xie et al, 2012; Baumung et al, 2016) utilizing the margin of exposure (MOE) approach (i.e., ratio of the toxicological threshold determined from various data bases to the estimated human intake; where compounds with MOE values less than 10,000 are considered high risk), determine both Cd and As to present considerable health related risks to the consumer; more so for Cd than As. On the other hand, while the maximum allowable inhalation of Ni, based on OSHA's PEL, from ECIG-generated aerosol was higher than the maximum allowable inhalation of Cd and As in mainstream smoke, Xie et al (2012), using the MOE approach, determined Ni in cigarette smoke to be less concerning than either Cd or As.…”

Cancer potencies and margin of exposure used for comparative risk assessment of heated tobacco products and electronic cigarettes aerosols with cigarette smoke

“…As such, they are designed to deliver nicotine to consumers with a pharmokinetic profile as close as possible to that of cigarettes to ensure that the smokers switch to the products successfully (Brossard et al 2017;Proctor 2018;Smith et al 2016). Baumung et al (2016) pointed out the urgency of integrating the risk related to nicotine when assessing the health risk related to the use of nicotine-containing products (including HTPs, ECs, or smokeless tobacco). The reasoning adopted by Baumung et al was based on the comparison of MOEs for various aerosol constituents, including nicotine.…”

“…MOEs were determined as described by Baumung et al (2016) and Lachenmeier et al (2018) with slight modifications. Briefly, for a given compound, its MOE is defined as the ratio of its toxicity effect level (the toxicological threshold of the compound) to its estimated human exposure: the toxicological threshold being either NOAEL, LOAEL, BMDL, or a derived reference dose or concentration (ADI, RfD, RfC, DNEL …).…”

A Review of Pulmonary Toxicity of Electronic Cigarettes in the Context of Smoking: A Focus on Inflammation

“…(270, 271). Risk assessment models are being developed to estimate these possible effects (272–274). The role of nicotine also needs to be considered, as it has both pro- and anti-inflammatory potential, making it unclear how nicotine content may mediate the effects of the other aerosol constituents.…”