Methodological Approaches for Risk Assessment of Tobacco and Related Products (original) (raw)
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Risk assessment of tobacco additives and smoke components : a method proposal
2012
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Nicotine was not included in previous eforts 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 deined 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 efects 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. Tobacco smoking can cause numerous diseases such as cardiovascular disease, chronic obstructive pulmonary disease and various types of cancer including lung, oral, esophageal and bladder cancer 1. Tobacco smoking has been classiied as " carcinogenic to humans " (group 1) by the International Agency for Research on Cancer 2. he World Health Organization (WHO) forecasts that cigarettes will kill nearly 10 million people per year globally by the year 2020 2 , and the reduction of smoking is crucial to achieve the goals of the " Global Action Plan for Prevention and Control of Non-Communicable Diseases (NCDs) " 3,4. Tobacco smoke is a complex chemical mixture containing more than 5000 components 2,5–10. Classes of compounds include but are not limited to neutral gases, carbon and nitrogen oxides, ethers, nitro compounds and metals 2,7,8,11. he available knowledge on the relationship between tobacco smoking and the development of cancer in humans is based primarily on epidemiological evidence. A large amount of such evidence has become available over the last decades 2. More than 70 carcinogens in tobacco smoke have been evaluated by the IARC monographs programme, and sixteen of these are classiied as carcinogenic to humans
Tobacco control, 2003
To provide a hazard prioritisation for reported chemical constituents of cigarette smoke using toxicological risk assessment principles and assumptions. The purpose is to inform prevention efforts using harm reduction. International Agency for Research on Cancer Monographs; California and US Environmental Protection Agency cancer potency factors (CPFs) and reference exposure levels; scientific journals and government reports from the USA, Canada, and New Zealand. This was an inclusive review of studies reporting yields of cigarette smoke constituents using standard ISO methods. Where possible, the midpoint of reported ranges of yields was used. Data on 158 compounds in cigarette smoke were found. Of these, 45 were known or suspected human carcinogens. Cancer potency factors were available for 40 of these compounds and reference exposure levels (RELs) for non-cancer effects were found for 17. A cancer risk index (CRI) was calculated by multiplying yield levels with CPFs. A non-cancer...
Addiction & Health, 2020
Background This study was conducted to evaluate the impact of filter on the eventual carcinogenic and non-carcinogenic risks caused by the main toxic constituents of popular cigarette brands in Iran. Methods At this laboratory study, the concentration of benzene, formaldehyde, arsenic, and cadmium in the mainstream smoke of 11 popular cigarette brands in Iran, on the without and with-filter modes was determined based on an established method. The hazard quotient (HQ), incremental lifetime cancer risk (ILCR), and mixture quantitative risk assessments (QRAs) were performed based on the QRA method recommended by United States Environmental Protection Agency (USEPA). Findings The mean of HQ due to benzene, formaldehyde, arsenic, and cadmium in without-filter cigarette smoke was from 3.96 to 3505. The findings indicated that the HQs related to benzene, formaldehyde, arsenic, and cadmium in cigarette smoke were decreased with filter by 48.3%, 25.3%, 37.6%, and 49.1%, respectively. The fil...
Archives of Toxicology, 2018
Consumers of combustible cigarettes are exposed to many different toxicologically relevant substances associated with negative health effects. Newly developed "heat not burn" (HNB) devices are able to contain lower levels of Harmful and Potentially Harmful Constituents (HPHCs) in their emissions compared to tobacco cigarettes. However, to develop toxicological risk assessment strategies, further independent and standardized investigations addressing HPHC reduction need to be done. Therefore, we generated emissions of a commercially available HNB product following the Health Canada Intense smoking regimen and analyzed total particulate matter (TPM), nicotine, water, aldehydes, and other volatile organic compounds (VOCs) that are major contributors to health risk. We show that nicotine yield is comparable to typical combustible cigarettes, and observe substantially reduced levels of aldehydes (approximately 80-95%) and VOCs (approximately 97-99%). Emissions of TPM and nicotine were found to be inconsistent during the smoking procedure. Our study confirms that levels of major carcinogens are markedly reduced in the emissions of the analyzed HNB product in relation to the conventional tobacco cigarettes and that monitoring these emissions using standardized machine smoking procedures generates reliable and reproducible data which provide a useful basis to assess exposure and human health risks.
Archives of Toxicology, 2020
Health risk associated with the use of combustible cigarettes is well characterized and numerous epidemiological studies have been published for many years. Since more than a decade, innovative non-combusted tobacco products have emerged like heated tobacco products (HTP) or electronic cigarettes (EC). Long-term effects of these new products on health remain, however, unknown and there is a need to characterize associated potential health risks. The time dedicated to epidemiological data generation (at least 20 to 40 years for cancer endpoint), though, is not compatible with innovative development. Surrogates need, therefore, to be developed. In this work, non-cancer and cancer risks were estimated in a range of HTP and commercial combustible cigarettes based upon their harmful and potentially harmful constituent yields in aerosols and smoke, respectively. It appears that mean lifetime cancer risk values were decreased by more than one order of magnitude when comparing HTPs and comm...
Tobacco control, 2011
Objective To determine how information on chemical constituents of different smokeless tobacco products (STPs) may be used in cancer risk assessment for regulatory purposes. Methods This study investigated select STP constituents potentially associated with significant cancer risk by applying a known toxicological risk assessment framework. Cancer risk estimates were obtained for selected constituents of STPs and a medicinal nicotine gum formulation with comparable toxicity information and also median concentration data on the GothiaTek analytes. The calculated cancer risk was considered 'unacceptable' if it exceeded the US Environmental Protection Agency's (USEPA's) benchmark of an 'acceptable' cancer risk of 10EÀ6. Results The cancer risk estimates derived from daily use of 10 g of STPs meeting the industry-set GothiaTek limits exceed the levels generally considered 'acceptable' by the USEPA at least 8000 times. Except for the medicinal nicotine tested, all the STP types, including the relatively lower tobacco specific nitrosamine (TSNA)-containing snus, were found to carry an 'unacceptable' cancer risk. The calculated cancer risks associated with the snus and the US moist snuff products were, respectively, at least 1000 times and 6000 times greater than the minimum acceptable. TSNA and cadmium are associated with the largest estimated cancer risks for all the STPs evaluated. Conclusions This study's findings provide an empirical risk assessment that could guide STP regulation using an existing toxicological assessment framework. The study findings question the scientific rationale of the industryset standards and highlight the need for regulatory actions to reduce specific toxicants in all STPs.
Regulatory Toxicology and Pharmacology, 2015
There is a drive toward the mandated lowering and reporting of selected toxicants in tobacco smoke. Several studies have quantified the mainstream cigarette emissions of toxicants, providing benchmark levels. Few, however, have examined how measured toxicant levels within a single product vary over time due to natural variation in the tobacco, manufacturing and measurement. In a single centre analysis, key toxicants were measured in the tobacco blend and smoke of 3R4F reference cigarette and three commercial products, each sampled monthly for 10 months. For most analytes, monthly variation was low (coefficient of variation <15%); but higher (P20%) for some compounds present at low (ppb) levels. Reporting toxicant emissions as a ratio to nicotine increased the monthly variation of the 9 analytes proposed for mandated lowering, by 1-2 percentage points. Variation in toxicant levels was generally 1.5-1.7-fold higher in commercial cigarettes compared with 3R4F over the 10-month period, but increased up to 3.5-fold for analytes measured at ppb level. The potential error (2CV) associated with single-point-intime sampling averaged $20%. Together, these data demonstrate that measurement of emissions from commercial cigarettes is associated with considerable variation for low-level toxicants. This variation would increase if the analyses were conducted in more than one laboratory.
2013
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 VP410 À5 Pa generally have RRs of 88% or greater, which do not vary appreciably with inhalation volume (IV). Compounds with VP510 À7 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.