Pharmacokinetic modeling of 4,4 '-methylenedianiline released from reused polyurethane dialyzer potting materials

4, 4'-Methylenedianiline (MDA) is a hydrolysis degradation product that can be released from polyurethanes commonly used in medical device application s. MDA is mutagenic and carcinogenic in animals. In humans, it is hepatotox ic, a known contact and respiratory allergen, and a suspected carcinogen. A physiologically based pharmacokinetic (PBPK) model was developed to estima te the absorption, distribution, metabolism, and excretion of MDA in patien ts exposed to MDA leached from the potting materials of hemodialyzers. A wo rst-case reuse situation and a single use case were investigated. The PBPK model included five tissue compartments: liver, kidney, gastrointestinal tr act, slowly perfused tissues, and richly perfused tissues. Physiological an d chemical parameters of a healthy individual used in the model were obtain ed from the literature. The model was calibrated using previously published kinetic studies of IV administered doses of(14) C-MDA to rats. The model w as validated using independent data published for MDA-exposed workers. The PBPK results indicated that dialysis patients who are exposed to MDA releas ed from dialyzers (new or reused) could accumulate low levels of MDA and me tabolites (total MDA) over time. (C) 2000 John Wiley & Sons, Inc.