<i>In vitro</i>-based human toxicity effect factors: challenges and opportunities for nanomaterial impact assessment

Romeo, Daina; Hischier, Roland; Nowack, Bernd; Fantke, Peter; Wick, Peter

doi:10.1039/d1en01014j

Cited by 6 publications

(4 citation statements)

References 99 publications

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“…The distribution, uptake, and metabolism of the material in mice are different from cellular and organoid models [ 50 ]. The resistance of models to nanotoxicity increases with their complexity.…”

Section: Resultsmentioning

confidence: 99%

Spike structure of gold nanobranches induces hepatotoxicity in mouse hepatocyte organoid models

Zhang,

Li,

Zhao

et al. 2024

J Nanobiotechnol

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Background Gold nanoparticles (GNPs) have been extensively recognized as an active candidate for a large variety of biomedical applications. However, the clinical conversion of specific types of GNPs has been hindered due to their potential liver toxicity. The origin of their hepatotoxicity and the underlying key factors are still ambiguous. Because the size, shape, and surfactant of GNPs all affect their properties and cytotoxicity. An effective and sensitive platform that can provide deep insights into the cause of GNPs’ hepatotoxicity in vitro is therefore highly desired. Methods Here, hepatocyte organoid models (Hep-orgs) were constructed to evaluate the shape-dependent hepatotoxicity of GNPs. Two types of GNPs with different nanomorphology, gold nanospheres (GNSs) and spiny gold nanobranches (GNBs), were synthesized as the representative samples. Their shape-dependent effects on mice Hep-orgs’ morphology, cellular cytoskeletal structure, mitochondrial structure, oxidative stress, and metabolism were carefully investigated. Results The results showed that GNBs with higher spikiness and tip curvature exhibited more significant cytotoxicity compared to the rounded GNSs. The spike structure of GNBs leads to a mitochondrial damage, oxidative stress, and metabolic disorder in Hep-orgs. Meanwhile, similar trends can be observed in HepG2 cells and mice models, demonstrating the reliability of the Hep-orgs. Conclusions Hep-orgs can serve as an effective platform for exploring the interactions between GNPs and liver cells in a 3D perspective, filling the gap between 2D cell models and animal models. This work further revealed that organoids can be used as an indispensable tool to rapidly screen and explore the toxic mechanism of nanomaterials before considering their biomedical functionalities.

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Section: Resultsmentioning

confidence: 99%

Spike structure of gold nanobranches induces hepatotoxicity in mouse hepatocyte organoid models

Zhang,

Li,

Zhao

et al. 2024

J Nanobiotechnol

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“…In addition, long term studies are required for the definition of human toxicity factors for LCA impact assessment. 37 states that the adaptation of life cycle impact assessment (LCIA) toxicity characterization methodology is not yet achieved for NMs/AdMa and in vitro data. The ibid authors stress that cross-discipline discussions are a fundamental step towards a successful integration of both new data sources and new substance types into LCIA.…”

Section: Resultsmentioning

confidence: 99%

Status, implications and challenges of European safe and sustainable by design paradigms applicable to nanomaterials and advanced materials

et al. 2023

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“…Within USEtox, a characterization factor is calculated as a combination of 1) a fate factor, which indicates how a substance is distributed in the environmental compartments following its emission; 2) an exposure factor, which describes the human uptake of the substance from the environmental compartments via multiple exposure pathways; 3) and an effect factor (EF), which relates the uptake of the substance to potential negative health effects . USEtox and its calculation principles have been developed for organic chemicals and metal ions , and is thus not adequate for nanomaterials in its original setting . A nanospecific fate model has been developed to calculate the fate factor for nanomaterials, while the exposure factor is either calculated according to existing methodologies or disregarded .…”

Section: Introductionmentioning

confidence: 99%

“…7 USEtox and its calculation principles have been developed for organic chemicals and metal ions 6,8 and is thus not adequate for nanomaterials in its original setting. 9 A nanospecific fate model has been developed to calculate the fate factor for nanomaterials, 10 while the exposure factor is either calculated according to existing methodologies or disregarded. 11 The EF is calculated from animal toxicological studies using those extrapolation factors (e.g., the interspecies extrapolation factor) needed to convert the animal results to a human chronic ED 50 , i.e., the lifetime dose generating a 50% increase in disease probability for humans.…”

Section: ■ Introductionmentioning

confidence: 99%

Approach toward In Vitro-Based Human Toxicity Effect Factors for the Life Cycle Impact Assessment of Inhaled Low-Solubility Particles

Romeo

Hischier

Nowack

et al. 2022

Environ. Sci. Technol.

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Today's scarcity of animal toxicological data for nanomaterials could be lifted by substituting in vivo data with in vitro data to calculate nanomaterials' effect factors (EF) for Life Cycle Assessment (LCA). Here, we present a step-by-step procedure to calculate in vitro-to-in vivo extrapolation factors to estimate human Benchmark Doses and subsequently in vitro-based EFs for several inhaled nonsoluble nanomaterials. Based on mouse data, the in vitrobased EF of TiO 2 is between 2.76 • 10 −4 and 1.10 • 10 −3 cases/(m 2 /g• kg intake), depending on the aerodynamic size of the particle, which is in good agreement with in vivo-based EFs (1.51 • 10 −4 −5.6 • 10 −2 cases/(m 2 /g•kg intake)). The EF for amorphous silica is in a similar range as for TiO 2 , but the result is less robust due to only few in vivo data available. The results based on rat data are very different, confirming the importance of selecting animal species representative of human responses. The discrepancy between in vivo and in vitro animal data in terms of availability and quality limits the coverage of further nanomaterials. Systematic testing on human and animal cells is needed to reduce the variability in toxicological response determined by the differences in experimental conditions, thus helping improve the predictivity of in vitro-to-in vivo extrapolation factors.

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In vitro-based human toxicity effect factors: challenges and opportunities for nanomaterial impact assessment

Abstract: Drawing the picture of the opportunities and challenges of using in vitro data to calculate effect factors in LCA.

Cited by 6 publications

References 99 publications

Spike structure of gold nanobranches induces hepatotoxicity in mouse hepatocyte organoid models

Spike structure of gold nanobranches induces hepatotoxicity in mouse hepatocyte organoid models

Status, implications and challenges of European safe and sustainable by design paradigms applicable to nanomaterials and advanced materials

Approach toward In Vitro-Based Human Toxicity Effect Factors for the Life Cycle Impact Assessment of Inhaled Low-Solubility Particles

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