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Probabilistic risk assessment of gold nanoparticles after intravenous administration by integrating in vitro and in vivo toxicity with physiologically based pharmacokinetic modeling.

ABSTRACT: This study aimed to conduct an integrated and probabilistic risk assessment of gold nanoparticles (AuNPs) based on recently published in vitro and in vivo toxicity studies coupled to a physiologically based pharmacokinetic (PBPK) model. Dose-response relationships were characterized based on cell viability assays in various human cell types. A previously well-validated human PBPK model for AuNPs was applied to quantify internal concentrations in liver, kidney, skin, and venous plasma. By applying a Bayesian-based probabilistic risk assessment approach incorporating Monte Carlo simulation, probable human cell death fractions were characterized. Additionally, we implemented in vitro to in vivo and animal-to-human extrapolation approaches to independently estimate external exposure levels of AuNPs that cause minimal toxicity. Our results suggest that under the highest dosing level employed in existing animal studies (worst-case scenario), AuNPs coated with branched polyethylenimine (BPEI) would likely induce ?90-100% cellular death, implying high cytotoxicity compared to <10% cell death induced by low-to-medium animal dosing levels, which are commonly used in animal studies. The estimated human equivalent doses associated with 5% cell death in liver and kidney were around 1 and 3?mg/kg, respectively. Based on points of departure reported in animal studies, the human equivalent dose estimates associated with gene expression changes and tissue cell apoptosis in liver were 0.005 and 0.5?mg/kg, respectively. Our analyzes provide insights into safety evaluation, risk prediction, and point of departure estimation of AuNP exposure for humans and illustrate an approach that could be applied to other NPs when sufficient data are available.

SUBMITTER: Cheng YH

PROVIDER: S-EPMC6051695 | biostudies-literature | 2018 Jun

REPOSITORIES: biostudies-literature

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Probabilistic risk assessment of gold nanoparticles after intravenous administration by integrating in vitro and in vivo toxicity with physiologically based pharmacokinetic modeling.

Cheng Yi-Hsien YH Riviere Jim E JE Monteiro-Riviere Nancy A NA Lin Zhoumeng Z

Nanotoxicology 20180414 5

This study aimed to conduct an integrated and probabilistic risk assessment of gold nanoparticles (AuNPs) based on recently published in vitro and in vivo toxicity studies coupled to a physiologically based pharmacokinetic (PBPK) model. Dose-response relationships were characterized based on cell viability assays in various human cell types. A previously well-validated human PBPK model for AuNPs was applied to quantify internal concentrations in liver, kidney, skin, and venous plasma. By applyin ...[more]

PMID: 29658401

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Dataset Information

Probabilistic risk assessment of gold nanoparticles after intravenous administration by integrating in vitro and in vivo toxicity with physiologically based pharmacokinetic modeling.

Publications

Probabilistic risk assessment of gold nanoparticles after intravenous administration by integrating in vitro and in vivo toxicity with physiologically based pharmacokinetic modeling.

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