title: Pharmacokinetic modeling of 4,4'-methylenedianiline released from reused polyurethane dialyzer potting materials.
abstract: 4, 4'-Methylenedianiline (MDA) is a hydrolysis degradation product that can be released from polyurethanes commonly used in medical device applications. MDA is mutagenic and carcinogenic in animals. In humans, it is hepatotoxic, a known contact and respiratory allergen, and a suspected carcinogen. A physiologically based pharmacokinetic (PBPK) model was developed to estimate the absorption, distribution, metabolism, and excretion of MDA in patients exposed to MDA leached from the potting materials of hemodialyzers. A worst-case reuse situation and a single use case were investigated. The PBPK model included five tissue compartments: liver, kidney, gastrointestinal tract, slowly perfused tissues, and richly perfused tissues. Physiological and chemical parameters of a healthy individual used in the model were obtained from the literature. The model was calibrated using previously published kinetic studies of IV administered doses of (14) C-MDA to rats. The model was validated using independent data published for MDA-exposed workers. The PBPK results indicated that dialysis patients who are exposed to MDA released from dialyzers (new or reused) could accumulate low levels of MDA and metabolites (total MDA) over time.
authors.affiliation: Food and Drug Administration, Center for Devices and Radiological Health, Rockville, Maryland 20852, USA. hml@cdrh.fda.gov
authors.forename: H M
authors.initials: HM
authors.lastname: Do Luu
authors.forename: J C
authors.initials: JC
authors.lastname: Hutter
mesh_terms: D000814:Aniline Compounds / Q000493:pharmacokinetics*; D000818:Animals; D001672:Biocompatible Materials / Q000493:pharmacokinetics*; D002273:Carcinogens / Q000493:pharmacokinetics*; D004864:Equipment and Supplies / Q000009:adverse effects*; D006801:Humans; D008954:Models, Biological; D011140:Polyurethanes / Q000378:metabolism* / Q000493:pharmacokinetics; D051381:Rats; D001559:Benzhydryl Compounds
chemical_list: D000814:Aniline Compounds; D001672:Biocompatible Materials; D002273:Carcinogens; D011140:Polyurethanes; C009505:4,4'-diaminodiphenylmethane; D001559:Benzhydryl Compounds