A novel application of the Margin of Exposure approach: Segregation of tobacco smoke toxicants

• Published in: Food and chemical toxicology 2011-11, Vol.49 (11), p.2921-2933
• Main Authors: Cunningham, F.H., Fiebelkorn, S., Johnson, M., Meredith, C.
• Format: Article
• Language: English
• Subjects: acetaldehyde; acrolein; Animals; Benchmark dose; benzo(a)pyrene; Biological and medical sciences; cadmium; carcinogenesis; dose response; ethylene oxide; formaldehyde; isoprene; Margin of exposure; Medical sciences; Modelling; respiratory system; respiratory tract diseases; Risk Assessment; risk management; Smoke - adverse effects; Smoke - analysis; smoking (habit); tobacco; Tobacco Products; Tobacco smoke; Tobacco, tobacco smoking; toxic substances; Toxicity Tests; Toxicology; vinyl chloride
• ISSN: 0278-6915; 1873-6351; 1873-6351
• DOI: 10.1016/j.fct.2011.07.019

► This paper describes the application of an MOE approach to tobacco smoke toxicants. ► MOEs were generally consistent for each smoke toxicant using diverse data sets. ► Segregation into priorities is discussed using 13 worked examples of MOEs. ► This approach facilitates prioritisation for more complex risk assessments. This paper presents a rationale for utilising a Margin of Exposure (MOE) approach to the segregation of tobacco smoke toxicants for risk assessment and management purposes. Future regulatory frameworks and product modifications aimed at tobacco harm reduction could utilise data that segregate toxicants using associations with specific diseases caused by cigarette smoking together with an indication of their relative contribution to that disease. Compounds with MOEs >10,000 accompanied by appropriate narrative are considered “low priority for risk management actions”. This paper applies the MOE model to representative examples of tobacco smoke toxicants associated with respiratory tract carcinogenesis and other respiratory diseases. A multiplicity of published dose response data on individual toxicants has been used to determine the range of possible MOE values, thus demonstrating the consistency of the relationships. Acetaldehyde, acrolein, acrylonitrile, cadmium, ethylene oxide, formaldehyde and isoprene all segregate with MOEs 10,000 and therefore may be considered as a low priority. 1,3-Butadiene, m-/p-cresols, NNK and NNN are assumed to segregate with high priority although additional data would be required to complete a full MOE assessment.