Biomaterial Database

A physiologically based pharmacokinetic model for 2,4-toluenediamine leached from polyurethane foam-covered breast implants. 1998

H M Luu, and J C Hutter, and H F Bushar

Center For Devices and Radiological Health, Food and Drug Administration, Rockville, MD 20852, USA.

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.

UI	MeSH Term	Description	Entries
D007275	Injections, Intravenous	Injections made into a vein for therapeutic or experimental purposes.	Intravenous Injections,Injection, Intravenous,Intravenous Injection
D007279	Injections, Subcutaneous	Forceful administration under the skin of liquid medication, nutrient, or other fluid through a hollow needle piercing the skin.	Subcutaneous Injections,Injection, Subcutaneous,Subcutaneous Injection
D008954	Models, Biological	Theoretical representations that simulate the behavior or activity of biological processes or diseases. For disease models in living animals, DISEASE MODELS, ANIMAL is available. Biological models include the use of mathematical equations, computers, and other electronic equipment.	Biological Model,Biological Models,Model, Biological,Models, Biologic,Biologic Model,Biologic Models,Model, Biologic
D010655	Phenylenediamines	Aniline compounds that contain two amino groups. They are used as a precursor in the synthesis of HETEROCYCLIC COMPOUNDS and POLYMERS. p-Phenylenediamine is used in the manufacture of HAIR DYES and is an ALLERGEN.
D011140	Polyurethanes	A group of thermoplastic or thermosetting polymers containing polyisocyanate. They are used as ELASTOMERS, as coatings, as fibers and as foams.	Polyisocyanates,Ostamer,Pellethane,Spandex,Ostamers,Pellethanes,Polyisocyanate,Polyurethane,Spandices
D002273	Carcinogens	Substances that increase the risk of NEOPLASMS in humans or animals. Both genotoxic chemicals, which affect DNA directly, and nongenotoxic chemicals, which induce neoplasms by other mechanism, are included.	Carcinogen,Oncogen,Oncogens,Tumor Initiator,Tumor Initiators,Tumor Promoter,Tumor Promoters,Initiator, Tumor,Initiators, Tumor,Promoter, Tumor,Promoters, Tumor
D005260	Female		Females
D006801	Humans	Members of the species Homo sapiens.	Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000465	Algorithms	A procedure consisting of a sequence of algebraic formulas and/or logical steps to calculate or determine a given task.	Algorithm
D000818	Animals	Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA.	Animal,Metazoa,Animalia