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

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 should be considered as high priority for exposure reduction research whereas benzo(a)pyrene and vinyl chloride segregate with an MOE >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.