Deriving exposure route-specific cancer slope factors of carcinogenic chemicals via PBK modeling

Carcinogenic chemicals entering the body via different exposure routes result in varying internal doses and thus influence the tumors development. The internal doses can be quantified using biotransfer factors (BTF) simulated by the physiologically based kinetic (PBK) model. This study proposed a modeling method to analyze the quantitative relationships between BTF and cancer slope factors (CSFs). When the CSF for one exposure route is known, the CSF values for the other two routes can be derived using the relationships. A total of 45 carcinogenic chemicals were selected, and their oral CSF (CSF_oral) and BTF values were collected for analysis. The results demonstrated that route-specific CSFs of chemicals can be different due to their physicochemical properties. In addition, the derived route-specific CSFs are further utilized to conduct a comprehensive cancer risk assessment. The results revealed that cancer risk caused by most environmental chemical exposure exceeded 1 × 10^-6, suggesting that long-term exposure to chemicals would pose certain human cancer risks. These findings highlight the importance of exposure route-specific CSFs for accurate cancer risk assessment and provide a scientific reference for environmental agencies to refine the risk assessment system.