Self-Organizing Map Analysis of Toxicity-Related Cell Signaling Pathways for Metal and Metal Oxide Nanoparticles

Ralló, Robert; France, Bryan; Liu, Rong; Nair, Sumitra; George, Saji; Damoiseaux, Robert; Giralt, Francesc; Nel, André E.; Bradley, Kenneth A.; Cohen, Yoram

doi:10.1021/es103606x

Cited by 83 publications

(98 citation statements)

References 38 publications

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“…Several groups have endeavored to develop efficient and inexpensive screening tools to correlate cellular toxicity with ENM characteristics such as size, shape and surface area [18,19,22,23]. High-throughput in vitro toxicity assays are utilized to assess multiple toxicity endpoints, in multiple cell lines, of libraries of ENMs over a range of exposure times and concentrations.…”

Section: Abstract: Dosimetry • Fate and Transport Modeling • Hazard Rmentioning

confidence: 99%

A Critical Review of in Vitro Dosimetry for Engineered Nanomaterials

Cohen¹,

DeLoid²,

Demokritou³

2015

Nanomedicine (Lond.)

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A major obstacle in the development of accurate cellular models for investigating nanobio interactions in vitro is determination of physiologically relevant measures of dose. Comparison of biological responses to nanoparticle exposure typically relies on administered dose metrics such as mass concentration of suspended particles, rather than the effective dose of particles that actually comes in contact with the cells over the time of exposure. Adoption of recently developed dosimetric methodologies will facilitate determination of effective dose delivered to cells in vitro, thereby improving the accuracy and reliability of in vitro screening data, validation of in vitro with in vivo data, and comparison across multiple datasets for the large variety of nanomaterials currently in the market.

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Section: Abstract: Dosimetry • Fate and Transport Modeling • Hazard Rmentioning

confidence: 99%

A Critical Review of in Vitro Dosimetry for Engineered Nanomaterials

Cohen¹,

DeLoid²,

Demokritou³

2015

Nanomedicine (Lond.)

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“…Data obtained with the HTS assays are evaluated to make predictions about those physico-chemical properties of NMs that may lead to the generation of adverse effects in vivo. Thereby, multi-parametric mechanism-based HTS approaches combined with heat-map clustering enable the development of nanostructure-activity relationships and NM grouping George et al, 2011;Liu et al, 2011;Rallo et al, 2011;Thomas et al, 2011;Nel et al, 2013).…”

Section: Research Activities Putting Nm Grouping Into Practicementioning

confidence: 99%

A critical appraisal of existing concepts for the grouping of nanomaterials

Arts

Hadi

Keene³

et al. 2014

Regulatory Toxicology and Pharmacology

121

104

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The grouping of substances serves to streamline testing for regulatory purposes. General grouping approaches for chemicals have been implemented in, e.g., the EU chemicals regulation. While specific regulatory frameworks for the grouping of nanomaterials are unavailable, this topic is addressed in different publications, and preliminary guidance is provided in the context of substance-related legislation or the occupational setting. The European Centre for Ecotoxicology and Toxicology of Chemicals Task Force on the Grouping of Nanomaterials reviewed available concepts for the grouping of nanomaterials for human health risk assessment. In their broad conceptual design, the evaluated approaches are consistent or complement each other. All go beyond the determination of mere structure-activity relationships and are founded on different aspects of the nanomaterial life cycle. These include the NM's material properties and biophysical interactions, specific types of use and exposure, uptake and kinetics, and possible early and apical biological effects. None of the evaluated grouping concepts fully take into account all of these aspects. Subsequent work of the Task Force will aim at combining the available concepts into a comprehensive 'multiple perspective' framework for the grouping of nanomaterials that will address all of the mentioned aspects of their life cycles.

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“…Therefore, the use of practical and rapid assessment platforms, such as high throughput screening method, for toxicity screening of ENMs would provide several benefits in terms of time and cost reductions. High throughput screening systems, which are capable of rapidly assessing multiple toxicants in multiple cell lines (at multiple doses), have already been used for assessing hazard potential of ENMs Harris, et al, 2013;Rallo, et al, 2011;Shaw, et al, 2008). We believe that HTS data will be extremely useful in near future for establishing nano-(Q)SAR models and identifying the parameters that are responsible for the toxicity of ENMs, as they include comprehensive toxicological information.…”

Section: Final Remarksmentioning

confidence: 99%

(Q)SAR modelling of nanomaterial toxicity: A critical review

et al. 2015

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There is an increasing recognition that nanomaterials pose a risk to human health, and that the novel engineered nanomaterials (ENMs) in the nanotechnology industry and their increasing industrial usage poses the most immediate problem for hazard assessment, as many of them remain untested. The large number of materials and their variants (different sizes and coatings for instance) that require testing and ethical pressure towards non-animal testing means that expensive animal bioassay is precluded, and the use of (quantitative) structure activity relationships ((Q)SAR) models as an alternative source of hazard information should be explored.(Q)SAR modelling can be applied to fill the critical knowledge gaps by making the best use of existing data, prioritize physicochemical parameters driving toxicity, and provide practical solutions to the risk assessment problems caused by the diversity of ENMs. This paper covers the core components required for successful application of (Q)SAR technologies to ENMs toxicity prediction, and summarizes the published nano-(Q)SAR studies and outlines the challenges ahead for nano-(Q)SAR modelling. It provides a critical review of (1) the present status of the availability of ENMs characterization/toxicity data, (2) the characterization of nanostructures that meets the need of (Q)SAR analysis, (3) the summary of published nano-(Q)SAR studies and their limitations, (4) the in silico tools for (Q)SAR screening of nanotoxicity and (5) the prospective directions for the development of nano-(Q)SAR models.

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Self-Organizing Map Analysis of Toxicity-Related Cell Signaling Pathways for Metal and Metal Oxide Nanoparticles

Cited by 83 publications

References 38 publications

A Critical Review of in Vitro Dosimetry for Engineered Nanomaterials

A Critical Review of in Vitro Dosimetry for Engineered Nanomaterials

A critical appraisal of existing concepts for the grouping of nanomaterials

(Q)SAR modelling of nanomaterial toxicity: A critical review

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