期刊
REGULATORY TOXICOLOGY AND PHARMACOLOGY
卷 144, 期 -, 页码 -出版社
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.yrtph.2023.105489
关键词
Stents; Nickel leaching; Physiologically based toxicokinetic (PBTK); models; Multi-objective optimization; Monte Carlo uncertainty estimation; Toxicological risk assessment
Contamination caused by metal ions leaching from medical device materials is a significant health problem. The use of modeling and simulation tools is recommended to support medical device submissions. An expanded physiologically based toxicokinetic model is used to predict the toxicological impact of medical devices.
Local and systemic contamination caused by metal ions leaching from medical device materials is a significant and continuing health problem. The increasing need for verification and validation, and the imposition of stringent government regulations to ensure that the products comply with the quality, safety, and performance standards, have led regulatory bodies worldwide to strongly recommend the use of modeling and simulation tools to support medical device submissions. A previously published physiologically based toxicokinetic (PBTK) model, is here expanded and enriched by an additional separate tissue compartment to better resemble normal physiology and by the introduction of time-dependent functions to describe all biokinetic parameters. The new model is exercised in conjunction with state-of-the-art probabilistic, Monte Carlo methodology to calculate the predictions' confidence intervals and incorporate variability associated with toxicological biodistribution studies. The quantitative consistency of the model-derived predictions is validated against reported data following the implantation of nickel-containing cardiovascular devices in humans and minipigs. Finally, a new methodology for compartmental toxicological risk assessment is presented that can be used for forward or reverse dosimetry. Our work is aimed at providing a computational tool to optimize the device design characteristics and safeguard that the substances released do not exceed permissible exposure limits.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据