Toward toxicity testing of nanomaterials in the 21st century: a paradigm for moving forward

Abstract

A challenge facing hazard identification and safety evaluation of engineered nanomaterials being introduced to market is the diversity and complexity of the types of materials with varying physicochemical properties, many of which can affect their toxicity by different mechanisms. In general, in vitro test systems have limited usefulness for hazard identification of nanoparticles due to various issues. Meanwhile, conducting chronic toxicity/carcinogenicity studies in rodents for every new nanomaterial introduced into the commerce is impractical if not impossible. New toxicity testing systems which rely on predictive, high‐throughput technologies may be the ultimate goal of evaluating the potential hazard of nanomaterials. However, at present, this approach alone is unlikely to succeed in evaluating the toxicity of the wide array of nanomaterials and requires validation from in vivo studies. This article proposes a paradigm for toxicity testing and elucidation of the molecular mechanisms of reference materials for specific nanomaterial classes/subclasses using short‐term in vivo animal studies in conjunction with high‐throughput screenings and mechanism‐based short‐term in vitro assays. The hazard potential of a particular nanomaterial can be evaluated by conducting only in vitro high‐throughput assays and mechanistic studies and comparing the data with those of the reference materials in the specific class/subclass—an approach in line with the vision for ‘Toxicity Testing in the 21st Century’ of chemicals. With well‐designed experiments, testing nanomaterials of varying/selected physicochemical parameters may be able to identify the physicochemical parameters contributing to toxicity. The data so derived could be used for the development of computer model systems to predict the hazard potential of specific nanoparticles based on property–activity relationships. WIREs Nanomed Nanobiotechnol 2012, 4:1–15. doi: 10.1002/wnan.162 This article is categorized under: Toxicology and Regulatory Issues in Nanomedicine > Toxicology of Nanomaterials

Cellular Mechanisms in Nanomaterial Internalization, Intracellular Trafficking, and Toxicity

“…Although studies in this field already existed before it was formally established, it is still not completely equipped with all the necessary scientific tools to properly evaluate all the possible toxic effects nanomaterials can elicit. Therefore, old techniques are being adapted, and new ones have been introduced to help evaluate the hazards and risks associated with nanomaterials (Hillegass et al 2010;Hussain et al 2009;Lai 2012;Lai et al 2012;Love et al 2012b;Marquis et al 2009). …”

Nanoinformatics: a new area of research in nanomedicine

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“…108,110 Nanoparticles can also interact with the immune system, provoking other side effects in humans. 113 All these analyses will produce datasets that can inform the design and construction of computational models and simulations that will attempt to predict the toxicity of nanoparticles.…”

“…There are various nanoscale materials for biological application that have failed because of their toxicity. 45,109,110 This failure is due to the complexity of living organisms, which makes it difficult to predict the consequences (ie, adverse reactions) of inserting a material into biological systems: the toxicity of some nanomaterials involves very complex pathways as well as specific interactions between biological tissues and synthetic materials and the transformations those materials may undergo. All these issues point to the need for diverse informatics methods and tools to augment basic research results and bring together information from all relevant lines of research and clinical tests.…”

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