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.

One‐pot synthesis of palm oil‐based polyester polyol for production of biodegradable and biocompatible polyurethane

“…Aliphatic diisocyanate was selected in the polyurethane production was mainly due to the degradation products are less toxic than that of degradation products yielded from the aromatic diisocyanate‐based polyurethane . The degradation products produced are for instance toluene diamine and 4,4′‐methylenedianiline, which are mutagenic and carcinogenic . Different isocyanate index ranged from 1.0 (PU 1), 1.1 (PU 2), and 1.2 (PU 3) was used to study the effect of isocyanate index on physical, mechanical, thermal, biodegradability, and biocompatibility properties of the polyurethanes.…”

Industrial, Biocide, and Cosmetic Chemical Inducers of Cholestasis

“…Methylenedianiline (Figure ) is used in the production of polyamides and epoxy resins as well as in the synthesis of 4,4′-methylenediphenyl diisocyanate, being a major component of polyurethanes. These polymers are applied in the manufacturing of insulation materials, automotive and aircraft parts, and medical devices. , …”

Nephrogenic fibrosing dermopathy

“…Dialysis patients who are exposed to those agents released from dialysers could accumulate low levels of 4,4′‐methylenedianiline and metabolites over time . 12 …”