Methodologies for the quantitative estimation of toxicant dose to cigarette smokers using physical, chemical and bioanalytical data

Abstract

Methodologies have been developed, described and demonstrated that convert mouth exposure estimates of cigarette smoke constituents to dose by accounting for smoke spilled from the mouth prior to inhalation (mouth-spill (MS)) and the respiratory retention (RR) during the inhalation cycle. The methodologies are applicable to just about any chemical compound in cigarette smoke that can be measured analytically and can be used with ambulatory population studies. Conversion of exposure to dose improves the relevancy for risk assessment paradigms. Except for urinary nicotine plus metabolites, biomarkers generally do not provide quantitative exposure or dose estimates. In addition, many smoke constituents have no reliable biomarkers. We describe methods to estimate the RR of chemical compounds in smoke based on their vapor pressure (VP) and to estimate the MS for a given subject. Data from two clinical studies were used to demonstrate dose estimation for 13 compounds, of which only 3 have urinary biomarkers. Compounds with VP > 10−5 Pa generally have RRs of 88% or greater, which do not vary appreciably with inhalation volume (IV). Compounds with VP < 10−7 Pa generally have RRs dependent on IV and lung exposure time. For MS, mean subject values from both studies were slightly greater than 30%. For constituents with urinary biomarkers, correlations with the calculated dose were significantly improved over correlations with mouth exposure. Of toxicological importance is that the dose correlations provide an estimate of the metabolic conversion of a constituent to its respective biomarker.

Vocal Fold Ion Transport and Mucin Expression Following Acrolein Exposure

“…Specifically, cigarette smoke plumes contain on average 890μM acrolein (Ayer and Yeager 1982). When acrolein is inhaled directly such as in the case of cigarette smoke, retention in the respiratory tract is estimated between 97–99%, (Bein and Leikauf 2011; St Charles et al 2013) further supporting the concentration chosen for the current study.…”

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

“…In this study, the cancer risk was estimated by the ILCR for each constituent, defined as follows: with ILCRj, the incremental lifetime cancer risk for the selected constituent; IUR j , the inhalation unit risk for the selected constituent (per μg/m 3 ); CY j , the mainstream aerosol constituent yield (µg/product); RR, the respiratory retention rate (%); MS, the mouth-spill rate (%); NCy, average number of product consumed per year (product/year); LE, life expectancy; SA, age at smoking initiation; and DBV, daily breathed volume (m 3 /day). The mouth-spill rate refers to the proportion of the undiluted aerosol that can be spilled out (consciously or not) or even blown from the mouth prior to inhalation (St. Charles et al 2013 ). The respiratory retention rate refers to the fraction of an aerosol constituent inhaled and retained in the respiratory tract, including both mouth and lung retention (St. Charles et al 2013 ).…”

“…The mouth-spill rate refers to the proportion of the undiluted aerosol that can be spilled out (consciously or not) or even blown from the mouth prior to inhalation (St. Charles et al 2013 ). The respiratory retention rate refers to the fraction of an aerosol constituent inhaled and retained in the respiratory tract, including both mouth and lung retention (St. Charles et al 2013 ).…”

Comparison of the impact of the Tobacco Heating System 2.2 and a cigarette on indoor air quality

“…380 ETS is an aged and diluted mixture of sidestream smoke emitted from the lit end of a smoldering 381 cigarette and exhaled mainstream smoke from the smoker. In addition, cigarette smoke spilled from the 382 mouth prior to inhalation (mouth-spill) may also contribute to ETS (St. Charles et al, 2013). 383…”