Use of hazard indices for a theoretical evaluation of cigarette smoke composition

The chemical composition of cigarette mainstream smoke (MS) has been quantitatively analyzed in multiple studies, often with the objective to toxicologically evaluate and compare various types of MS. Increases and decreases in yields of constituents between MS types can only be consolidated if these yields are compared on the basis of toxicological properties of the individual constituents. For the risk assessment of various complex mixtures including MS, a hazard index (HI) approach has been used that requires weighing of the exposure to individual MS constituents by cancer and noncancer potency values. The objective of the current study is to review the past uses of the HI concept for MS and smokeless tobacco and discuss strengths and limitations of using this concept. Published information as well as information made available on the Web was used. The HI concept has been applied to MS for determining and comparing theoretical lifetime risks, for consumer communication, for the prioritization of constituents for reduction, for ingredient assessment, and for the selection of constituents for regulation. The limitations of this approach are associated with the limited number of MS constituents with available yield data, the gaps and uncertainties in available potency values, the application to relatively high exposure concentrations, and the default assumption of additivity. The derived theoretical noncancer index is dominated by acrolein to an extent that there seems to be not much advantage in using the HI concept for noncancer assessments. The derived theoretical cancer index is dominated by genotoxic carcinogens of the MS vapor phase and may thus complement currently used toxicological assays in a tiered evaluation approach. As is the case for every other assay and interpretation model, the HI concept needs to be applied with its limitations and weaknesses in mind. Its best application is for comparative purposes. It should be kept in mind that the HI concept is a theoretical concept and does not provide actual risk information.