Key words: pharmacokinetic modeling, TDA, biomaterial degradation, computer simulation, carcinogenicity, tech support, research
Physiologically-based pharmacokinetic modeling, also known as PBPK, has been widely used in the study of drugs. But to date, little progress has been made in applying this approach to assess the hazard of medical devices. A known mutagen and rodent carcinogen, 2,4-Toluenediamine (2,4-TDA), was found as a degradation product of the polyester urethane cover of the Meme breast implants in vivo. The carcinogenicity of 2,4-TDA was studied in mice and rats and found to be dose-dependent and vary with the route and species tested. PBPK modeling is used in this study to describe the fate of 2,4-TDA in the rat. The model was calibrated with data derived from studies of 2,4-TDA related to the biodegradation of the PU foam. Advantages and disadvantages of using this computer-simulated PBPK model as a tool to predict chemical exposure from biomaterial degradation are discussed. This model of ordinary differential equations was solved using Mathcad PLUS 6.0 (MathSoft, Cambridge, Massachusetts).