A physiologically based pharmacokinetic model for 2,4-toluenediamine leached from polyurethane foam-covered breast implants.
Physiologically based pharmacokinetic (PBPK) modeling was used to assess the low-dose exposure of patients to the carcinogen 2, 4-toluenediamine (2,4-TDA) released from the degradation of the polyester urethane foam (PU) used in Meme silicone breast implants. The tissues are represented as five compartments: liver, kidney, gastrointestinal tract, slowly perfused tissues (e.g., fat), and richly perfused tissues (e.g., muscle). The PBPK model was fitted to the plasma and urine concentrations of 2,4-TDA and its metabolite 4-AAT (4-N-acetyl-2-amino toluene) in rats given low doses of 2, 4-TDA intravenously and subcutaneously. The rat model was extrapolated to simulate oral and implant routes in rats. After adjusting for human physiological parameters, the model was then used to predict the bioavailability of 2,4-TDA released from a typical 4.87-g polyester urethane foam implant found in a patient who weighed 58 kg with the Meme and had the breast implant for 10 years. A quantitative risk assessment for 2,4-TDA was performed and the polyester urethane foam did present an unreasonable risk to health for the patient.
Luu
H M
HM
Center For Devices and Radiological Health, Food and Drug Administration, Rockville, MD 20852, USA.
Hutter
J C
JC
Bushar
H F
HF
D000465:Algorithms; D000818:Animals; D018427:Breast Implants / Q000009:adverse effects*; D002273:Carcinogens / Q000737:chemistry / Q000493:pharmacokinetics*; D005260:Female; D006801:Humans; D007275:Injections, Intravenous; D007279:Injections, Subcutaneous; D008954:Models, Biological; D010655:Phenylenediamines / Q000737:chemistry / Q000493:pharmacokinetics*; D011140:Polyurethanes / Q000737:chemistry*; D051381:Rats; D014018:Tissue Distribution
D002273:Carcinogens; D010655:Phenylenediamines; D011140:Polyurethanes; C010914:2,4-diaminotoluene