Dataset Information

Toxicity-based toxicokinetic/toxicodynamic assessment of bioaccumulation and nanotoxicity of zerovalent iron nanoparticles in Caenorhabditis elegans.

ABSTRACT: Elucidating the relationships between the toxicity-based-toxicokinetic (TBTK)/toxicodynamic (TD) properties of engineered nanomaterials and their nanotoxicity is crucial for human health-risk analysis. Zerovalent iron (Fe⁰) nanoparticles (NPs) are one of the most prominent NPs applied in remediating contaminated soils and groundwater. However, there are concerns that Fe⁰NP application contributes to long-term environmental and human health impacts. The nematode Caenorhabditis elegans is a surrogate in vivo model that has been successfully applied to assess the potential nanotoxicity of these nanomaterials. Here we present a TBTK/TD approach to appraise bioaccumulation and nanotoxicity of Fe⁰NPs in C. elegans. Built on a present C. elegans bioassay with estimated TBTK/TD parameters, we found that average bioconcentration factors in C. elegans exposed to waterborne and food-borne Fe⁰NPs were ~50 and ~5×10^-3, respectively, whereas 10% inhibition concentrations for fertility, locomotion, and development, were 1.26 (95% CI 0.19-5.2), 3.84 (0.38-42), and 6.78 (2.58-21) ?g·g^-1, respectively, implicating that fertility is the most sensitive endpoint in C. elegans. Our results also showed that biomagnification effects were not observed in waterborne or food-borne Fe⁰NP-exposed worms. We suggest that the TBTK/TD assessment for predicting NP-induced toxicity at different concentrations and conditions in C. elegans could enable rapid selection of nanomaterials that are more likely to be nontoxic in larger animals. We conclude that the use of the TBTK/TD scheme manipulating C. elegans could be used for rapid evaluation of in vivo toxicity of NPs or for drug screening in the field of nanomedicine.

SUBMITTER: Yang YF

PROVIDER: S-EPMC5500513 | biostudies-literature | 2017

REPOSITORIES: biostudies-literature

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Toxicity-based toxicokinetic/toxicodynamic assessment of bioaccumulation and nanotoxicity of zerovalent iron nanoparticles in Caenorhabditis elegans.

Yang Ying-Fei YF Lin Yi-Jun YJ Liao Chung-Min CM

International journal of nanomedicine 20170626

Elucidating the relationships between the toxicity-based-toxicokinetic (TBTK)/toxicodynamic (TD) properties of engineered nanomaterials and their nanotoxicity is crucial for human health-risk analysis. Zerovalent iron (Fe0) nanoparticles (NPs) are one of the most prominent NPs applied in remediating contaminated soils and groundwater. However, there are concerns that Fe0NP application contributes to long-term environmental and human health impacts. The nematode Caenorhab ...[more]

PMID: 28721038

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Project description:Providing reliable environmental quality standards (EQSs) is a challenging issue in environmental risk assessment (ERA). These EQSs are derived from toxicity endpoints estimated from dose-response models to identify and characterize the environmental hazard of chemical compounds released by human activities. These toxicity endpoints include the classical x% effect/lethal concentrations at a specific time t (EC/LC(x, t)) and the new multiplication factors applied to environmental exposure profiles leading to x% effect reduction at a specific time t (MF(x, t), or denoted LP(x, t) by the EFSA). However, classical dose-response models used to estimate toxicity endpoints have some weaknesses, such as their dependency on observation time points, which are likely to differ between species (e.g., experiment duration). Furthermore, real-world exposure profiles are rarely constant over time, which makes the use of classical dose-response models difficult and may prevent the derivation of MF(x, t). When dealing with survival or immobility toxicity test data, these issues can be overcome with the use of the general unified threshold model of survival (GUTS), a toxicokinetic-toxicodynamic (TKTD) model that provides an explicit framework to analyse both time- and concentration-dependent data sets as well as obtain a mechanistic derivation of EC/LC(x, t) and MF(x, t) regardless of x and at any time t of interest. In ERA, the assessment of a risk is inherently built upon probability distributions, such that the next critical step is to characterize the uncertainties of toxicity endpoints and, consequently, those of EQSs. With this perspective, we investigated the use of a Bayesian framework to obtain the uncertainties from the calibration process and to propagate them to model predictions, including LC(x, t) and MF(x, t) derivations. We also explored the mathematical properties of LC(x, t) and MF(x, t) as well as the impact of different experimental designs to provide some recommendations for a robust derivation of toxicity endpoints leading to reliable EQSs: avoid computing LC(x, t) and MF(x, t) for extreme x values (0 or 100%), where uncertainty is maximal; compute MF(x, t) after a long period of time to take depuration time into account and test survival under pulses with different periods of time between them.

Dataset Information

Toxicity-based toxicokinetic/toxicodynamic assessment of bioaccumulation and nanotoxicity of zerovalent iron nanoparticles in Caenorhabditis elegans.

Publications

Toxicity-based toxicokinetic/toxicodynamic assessment of bioaccumulation and nanotoxicity of zerovalent iron nanoparticles in <i>Caenorhabditis elegans</i>.

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