A PHYSIOLOGICALLY-BASED PHARMACOKINETIC MODEL FOR 2,4-TOLUENEDIAMINE LEACHED FROM POLYURETHANE FOAM-COVERED BREAST IMPLANTS

Physiologically based pharmacokinetic (PBPK) modeling was used to asse ss the low-dose exposure of patients to the carcinogen 2,4-toluenediam ine (2,4-TDA) released from the degradation of the polyester urethane foam (PU) used in Meme silicone breast implants. The tissues are repre sented as five compartments: liver, kidney, gastrointestinal tract, sl owly perfused tissues (e.g.; fat), and richly perfused tissues (e.g., muscle). The PBPK model was fitted to the plasma and urine concentrati ons of 2,4-TDA and its metabolite 4-AAT (4-N-acetyl-2-amino toluene) i n mts given low doses of 2,4-TDA intravenously and subcutaneously. The rat model was extrapolated to simulate oral and implant routes in rat s. After adjusting for human physiological parameters, the model was t hen used to predict the bioavailability of 2,4-TDA released from a typ ical 4.87-g polyester methane foam implant found in a patient who weig hed 58 kg with the Meme and had the breast implant for 10 years. A qua ntitative risk assessment for 2,4-TDA was performed and the polyester urethane foam did present an unreasonable risk to health for the patie nt.