Free the rats, mice, and zebrafish from the labs—replace them with in vitro assays to test nanomaterial toxcicity

The July 9, 2012 Nanowerk Spotlight article by Carl Walkey (of the University of Toronto) focuses on research by Dr. André Nel and his coworkers at the California NanoSystems Institute (CNSI) and the University of California Los Angeles (UCLA) on replacing small animal model testing for nanomaterial toxicity with in vitro assays,

Currently, small animal models are the ‘gold standard’ for nanomaterial toxicity testing. In a typical assessment, researchers introduce a nanomaterial into a series of laboratory animals, generally rats or mice, or the ‘workhorse’ of toxicity testing – zebrafish (see: “High content screening of zebrafish greatly speeds up nanoparticle hazard assessment”). They then examine where the material accumulates, whether it is excreted or retained in the animal, and the effect it has on tissue and organ function. A detailed understanding often requires dozens of animals and can take many months to complete for a single formulation. The current infrastructure and funding for animal testing is insufficient to support the evaluation of all nanomaterials currently in existence, let alone those that will be developed in the near future. This is creating a growing deficit in our understanding of nanomaterial toxicity, which fuels public apprehension towards nanotechnology.

Dr. André Nel and his coworkers at the California NanoSystems Institute (CNSI) and the University of California Los Angeles (UCLA) are taking a fundamentally different approach to nanomaterial toxicity testing.

Nel believes that, under the right circumstances, resource-intensive animal experiments can be replaced with comparatively simple in vitro assays.  The in vitro assays are not only less costly, but they can also be performed using high throughput (HT) techniques. By using an in vitro HT screening approach, comprehensive toxicological testing of a nanomaterial can be performed in a matter of days. Rapid information gathering will allow stakeholders to make rational, informed decisions about nanomaterials during all phases of the development process, from design to deployment.

I’ve excerpted a brief description of Nel’s approach,

Rather than using in vitro systems as direct substitutes for the in vivo case, Nel is using a mechanistic approach to connect cellular responses to more complex biological responses, attempting to employ mechanisms that are engaged at both levels and reflective of specific nanomaterial properties.

“You need to align what you test at a cellular level with what you want to know at the in vivo” says Nel. “If oxidative stress at the cellular level is a key initiating element, then by screening for this outcome in cells you more are likely to yield something more predictive of the in vivo outcome. We can do a lot of our mechanistic work at an implementation level that allows development of predictive screening assays.”

By measuring many relevant mechanistic responses, and integrating the results, Nel believes that the in vivo behavior of a nanomaterial can be accurately predicted, provided that enough thinking goes into the devising the systems biology approach to safety assessment.

According to Walkey’s article, this approach could result in a ‘reverse’ nanomaterial development process,

Nel’s approach will influence not only the way in which nanomaterial toxicity is assessed, but also the way in which nanomaterials are developed. Currently, nanomaterials are designed to meet the need of a particular application. Toxicity is then evaluated retrospectively. Formulations that exhibit unacceptable toxicity at that point may be abandoned after a significant investment in development. Because Nel’s approach generates toxicity information much faster than traditional techniques, it will be possible to integrate toxicity during the design of a new nanomaterial. The proactive characterization of nanomaterial toxicity will provide feedback during the design process, producing formulations that maximize efficacy and minimize risk.

This is a very interesting article (illustrated with images and peppered with accessibly explanations of the issues) for anyone following the ‘nanomaterial toxicology’ story.

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