Toxicological approaches for the quantitative inhalation risk assessment of toxic metals from tobacco smoke: application on the deterministic and probabilistic inhalation risk assessment of cadmium for Austrian smokers.

OBJECTIVE The objective of this study was the assessment of risks from inhalation exposure of Austrian smokers to cadmium through established toxicological approaches with emphasis on the exposure assessment component, which is challenging regarding the actual amount of metal that is inhaled and the simulation of the smoking pattern. MATERIALS AND METHODS Exposure assessment comprised an estimation of the proportion of cadmium inhaled through smoking and actual occurrence data in tobacco products and survey smoking habits, which were integrated in alternative scenarios through a deterministic and a probabilistic Monte Carlo simulation method. Risks were characterized through the comparison of the exposure with health-based guidance values, as well as through the assessment of the excess lifetime cancer risk (ELCR), the non-cancer hazard quotient (NCHQ), and the margin of exposure (MOE). The strengths, the uncertainties, and the limitations of the different methodologies were discussed. RESULTS AND DISCUSSION Upper exposures are close or exceed the Permitted Daily Exposure. Respiratory ELCRs are unacceptable compared to the benchmark range of 1.0E-06 to 1.0E-04. Renal and respiratory NCHQs exceed the target value of 1.0 by 3- to 17-fold. MOEs are not protective enough for cancer and non-cancer effects. The amount of cadmium that reaches the lung is a key source of uncertainty. CONCLUSION Probabilistic estimates provide a refined capture of the actual inhalation exposure. Risk estimates and gender and age profiles are alarming, especially for young smokers. Application of toxicological approaches, combined with realistic assessment of the inhalation exposure levels, can support risk communication and management.