PBPK Models in Cancer Risk Assessment

By facilitating the simulation of the dose metrics for use in cancer dose-response analysis, the PBPK models address the uncertainty associated with interspecies, route-to-route, and high-dose to low-dose extrapolations (Andersen et al. 1993 Andersen and Krishnan 1994 Clewell et al. 2002a Clewell and Andersen 1987 Melnick and Kohn 2000). Since the first demonstration of the application of PBPK models in cancer risk assessment by Andersen and co-workers in 1987, there have been substantial efforts to evaluate the appropriate dose metrics and cancer risk associated with a number of other volatile organic chemicals using the PBPK modeling approach (Table 21.3). These risk assessments have been based on the PBPK model simulations of a variety of dose metrics that reflect the current state 

TABLE 21.3. Examples of PBPK Models Developed for Assessing Dose Metrics and Cancer Risks 

Chemical Extrapolation Performed Most Recent Human Risk Estimation Approach Reference 

4-Dioxane HL, IS Unit risk Reitz et al. (1990b), Leimg and Paustenbach (1990), Sweeney et al. (2008) 

Methylene chloride HL, IS Unit risk Andersen et al. (1987), Marino et al. (2006), David et al. (2006), Marino and Starr (2007) 

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PHYSIOLOGICALLY BASED PHARMACOKINETIC (PBPK) MODELS IN CANCER RISK ASSESSMENT... 

CHAPTER 21 PBPK MODELS IN CANCER RISK ASSESSMENT TABLE 21.4. Dose-Response Assessment for Angiosarcoma Induced by Vinyl Chloride... 

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