title: Computational multiscale toxicodynamic modeling of silver and carbon nanoparticle effects on mouse lung function.
abstract: A computational, multiscale toxicodynamic model has been developed to quantify and predict pulmonary effects due to uptake of engineered nanomaterials (ENMs) in mice. The model consists of a collection of coupled toxicodynamic modules, that were independently developed and tested using information obtained from the literature. The modules were developed to describe the dynamics of tissue with explicit focus on the cells and the surfactant chemicals that regulate the process of breathing, as well as the response of the pulmonary system to xenobiotics. Alveolar type I and type II cells, and alveolar macrophages were included in the model, along with surfactant phospholipids and surfactant proteins, to account for processes occurring at multiple biological scales, coupling cellular and surfactant dynamics affected by nanoparticle exposure, and linking the effects to tissue-level lung function changes. Nanoparticle properties such as size, surface chemistry, and zeta potential were explicitly considered in modeling the interactions of these particles with biological media. The model predictions were compared with in vivo lung function response measurements in mice and analysis of mice lung lavage fluid following exposures to silver and carbon nanoparticles. The predictions were found to follow the trends of observed changes in mouse surfactant composition over 7 days post dosing, and are in good agreement with the observed changes in mouse lung function over the same period of time.
authors: Department of Environmental and Occupational Medicine, Robert Wood Johnson Medical School, Rutgers University, Piscataway, New Jersey, United States of America ; Department of Chemical and Biochemical Engineering, Rutgers University, Piscataway, New Jersey, United States of America.
authors: Dwaipayan
authors: D
authors: Mukherjee
authors: Danielle
authors: D
authors: Botelho
authors: Andrew J
authors: AJ
authors: Gow
authors: Junfeng
authors: J
authors: Zhang
authors: Panos G
authors: PG
authors: Georgopoulos
mesh_terms: D000818:Animals; D003198:Computer Simulation; D008168:Lung / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D053768:Metal Nanoparticles; D051379:Mice; D008954:Models, Biological; D037742:Nanotubes, Carbon; D010316:Particle Size; D012129:Respiratory Function Tests; D015262:Xenobiotics / Q000009:adverse effects / Q000493:pharmacokinetics
chemical_list: D037742:Nanotubes, Carbon; D015262:Xenobiotics