TSRC, Tob. Sci. Res. Conf., 2019, 73, abstr. 081

Review of relevant toxicological data using bmds to estimate inhalation unit risk for risk assessment practices

ITG Brands, Greensboro, NC, USA

Carcinogen Risk Assessment relies in the use of inhalation unit risk (IUR) values often published by National or International government agencies. However, many smoke analytes lack IURs or have conflicting values due to different interpretation of the tumorigenic data (critical effect) or the model used to fit the data. This leads to incomplete risk assessment and increase uncertainty in the risk assessment process. The objective of this work is to review the availability of toxicological data for selective smoke analytes, determine data limitations, re-calculate IUR’s in case of conflicting values, or estimate IUR’s for selective smoke analytes when they have not been previously reported. The Benchmark Dose (BMD) approach was implemented by modeling tumor data and exposure to establish a dose-response relationship. For mutagenic substances the practice is to use linear extrapolation to low doses as a conservative approach. The IUR was derived following this extrapolation and the benchmark dose lower bound (BMDL) at different response levels was also estimated. The BMDL at the relevant response level, e.g. 10% (BMDL10) could be used as the Point of Departure (POD). The use of the BMD approach confirmed previously published IUR for a strong nitrosamine carcinogen. Although assumptions on critical effects at low doses, referenced in published literature, could increase the IUR. In the case of a weak carcinogen with limited information and no known published IUR, the approach resulted in values that could be used as the IUR for risk assessment practices. In summary, the use of the BMD approach to determine POD as the reference for health effects can be expanded to other analytes with debatable IURs published by different agencies or in public literature.