Modeling In Vivo Interactions of Engineered Nanoparticles in the Pulmonary Alveolar Lining Fluid

Mukherjee, Dwaipayan; Porter, Alexandra E.; Ryan, Mary P.; Schwander, Stephan; Chung, Kian Fan; Tetley, Teresa D.; Zhang, Junfeng Jim; Georgopoulos, Panos G.

doi:10.3390/nano5031223

Cited by 6 publications

(8 citation statements)

References 52 publications

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“…Neither the ISDD nor ADSRM models consider the interaction of MNs with molecules present in the test system media. To overcome this limitation in the ASDRM model, the authors [54] extended the ADSRM model to consider the interaction of MNs with various fractions of lipids and surfactant proteins in the model. Another enhancement worth mentioning is the semi-analytical solution for the ISDD model developed by Mahnama et al [55] .…”

Section: Results On Available Pb Models Applicable To Mnsmentioning

confidence: 99%

“…However, the model can predict the dissolution of silver MNs. In a further publication, the same authors added the assessment of MN interaction with various fractions of lipids and surfactant proteins of the alveolar lining fluid, and applied the model also to 20–110 nm gold MNs and 600 nm SiO 2 particles [54] .…”

Section: Discussionmentioning

confidence: 99%

“…5 . In vitro dosimetry models collected in our inventory provide as an output the estimation of the time-dependent fraction of administered particles that deposit on cells [45] , [53] , [54] , [55] , or the spatial distribution of MNs in the extracellular space [56] .…”

Section: Discussionmentioning

confidence: 99%

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Physiologically based mathematical models of nanomaterials for regulatory toxicology: A review

Lamon

Asturiol

Vílchez

et al. 2019

Computational Toxicology

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The development of physiologically based (PB) models to support safety assessments in the field of nanotechnology has grown steadily during the last decade. This review reports on the availability of PB models for toxicokinetic (TK) and toxicodynamic (TD) processes, including in vitro and in vivo dosimetry models applied to manufactured nanomaterials (MNs). In addition to reporting on the state-of-the-art in the scientific literature concerning the availability of physiologically based kinetic (PBK) models, we evaluate their relevance for regulatory applications, mainly considering the EU REACH regulation. First, we performed a literature search to identify all available PBK models. Then, we systematically reported the content of the identified papers in a tailored template to build a consistent inventory, thereby supporting model comparison. We also described model availability for physiologically based dynamic (PBD) and in vitro and in vivo dosimetry models according to the same template. For completeness, a number of classical toxicokinetic (CTK) models were also included in the inventory. The review describes the PBK model landscape applied to MNs on the basis of the type of MNs covered by the models, their stated applicability domain, the type of (nano-specific) inputs required, and the type of outputs generated. We identify the main assumptions made during model development that may influence the uncertainty in the final assessment, and we assess the REACH relevance of the available models within each model category. Finally, we compare the state of PB model acceptance for chemicals and for MNs. In general, PB model acceptance is limited by the absence of standardised reporting formats, psychological factors such as the complexity of the models, and technical considerations such as lack of blood:tissue partitioning data for model calibration/validation.

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Section: Results On Available Pb Models Applicable To Mnsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Physiologically based mathematical models of nanomaterials for regulatory toxicology: A review

Lamon

Asturiol

Vílchez

et al. 2019

Computational Toxicology

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“…Model predictions for agglomeration and dissolution were compared to in vitro measurements for various MNMs, coating materials, and incubation media, and found to be consistent with the measurements. The fate, transport, and effects of MNMs throughout the lung were also modelled to predict particle transport across the air/biological fluid interface and the final expected dose for both coated and uncoated particles[73] [74].…”

Section: Resultsmentioning

confidence: 99%

Advancing the Understanding of Environmental Transformations, Bioavailability and Effects of Nanomaterials, an International US Environmental Protection Agency—UK Environmental Nanoscience Initiative Joint Program

Lasat

Chung

Lead

et al. 2018

JEP

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Nanotechnology has significant economic, health, and environmental benefits, including renewable energy and innovative environmental solutions. Manufactured nanoparticles have been incorporated into new materials and products because of their novel or enhanced properties. These very same properties also have prompted concerns about the potential environmental and human health hazard and risk posed by the manufactured nanomaterials. Appropriate risk management responses require the development of models capable of predicting the environmental and human health effects of the nanomaterials. Development of predictive models has been hampered by a lack of information concerning the environmental fate, behavior and effects of manufactured nanoparticles. The United Kingdom (UK) Environmental Nanoscience Initiative and the United States (US) Environmental Protection Agency have developed an international research program to enhance the knowledgebase and develop risk-predicting models for manufactured nanoparticles. Here we report selected highlights of the program as it sought to maximize the complementary strengths of the transatlantic scientific communities by funding three integrated US-UK consortia to investigate the transformation of these nanoparticles in terrestrial, aquatic, and atmospheric environment. Research results demonstrate there is a functional relationship between the physicochemical properties of environmentally transformed nanomaterials and their effects and that this relationship is amenable to modeling. In addition, the joint transatlantic program has allowed the leveraging of additional funding, promoting transboundary scientific collaboration.

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“…As airborne NPs are mainly absorbed by respiratory routes, some of the toxic effects of NPs on lungs have been described in both humans and experimental animals, being characterized mostly by inducible inflammatory reactions [ 144 ]. Still, inhaled NPs have a very small size and can be arrested from alveoli into other tissues by the bloodstream, which may lead to systemic harmful effects [ 148 ]. Indeed, it has been demonstrated that pulmonary instillation of titanium dioxide (TiO2) NPs has resulted in increased plaque deposits in atherosclerosis-prone apolipoprotein E-deficient mice [ 149 ].…”

Section: Cellular and Molecular Mechanisms Of Toxicity On Hematopomentioning

confidence: 99%

Cellular and Molecular Mechanisms of Environmental Pollutants on Hematopoiesis

Scharf

Broering

Rocha

et al. 2020

IJMS

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Hematopoiesis is a complex and intricate process that aims to replenish blood components in a constant fashion. It is orchestrated mostly by hematopoietic progenitor cells (hematopoietic stem cells (HSCs)) that are capable of self-renewal and differentiation. These cells can originate other cell subtypes that are responsible for maintaining vital functions, mediate innate and adaptive immune responses, provide tissues with oxygen, and control coagulation. Hematopoiesis in adults takes place in the bone marrow, which is endowed with an extensive vasculature conferring an intense flow of cells. A myriad of cell subtypes can be found in the bone marrow at different levels of activation, being also under constant action of an extensive amount of diverse chemical mediators and enzymatic systems. Bone marrow platelets, mature erythrocytes and leukocytes are delivered into the bloodstream readily available to meet body demands. Leukocytes circulate and reach different tissues, returning or not returning to the bloodstream. Senescent leukocytes, specially granulocytes, return to the bone marrow to be phagocytized by macrophages, restarting granulopoiesis. The constant high production and delivery of cells into the bloodstream, alongside the fact that blood cells can also circulate between tissues, makes the hematopoietic system a prime target for toxic agents to act upon, making the understanding of the bone marrow microenvironment vital for both toxicological sciences and risk assessment. Environmental and occupational pollutants, therapeutic molecules, drugs of abuse, and even nutritional status can directly affect progenitor cells at their differentiation and maturation stages, altering behavior and function of blood compounds and resulting in impaired immune responses, anemias, leukemias, and blood coagulation disturbances. This review aims to describe the most recently investigated molecular and cellular toxicity mechanisms of current major environmental pollutants on hematopoiesis in the bone marrow.

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Modeling In Vivo Interactions of Engineered Nanoparticles in the Pulmonary Alveolar Lining Fluid

Cited by 6 publications

References 52 publications

Physiologically based mathematical models of nanomaterials for regulatory toxicology: A review

Physiologically based mathematical models of nanomaterials for regulatory toxicology: A review

Advancing the Understanding of Environmental Transformations, Bioavailability and Effects of Nanomaterials, an International US Environmental Protection Agency—UK Environmental Nanoscience Initiative Joint Program

Cellular and Molecular Mechanisms of Environmental Pollutants on Hematopoiesis

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