Mandatory nanotoxicology testing is just around the corner. Are you ready?
As more nanotechnology products enter the marketplace, they are coming under intense scrutiny by the government, industry, and consumers. The focus of this concern? Human exposure and safety. In the past six months, government agencies, industry, and environmental stakeholders have made recommendations for evaluating the safety of nanomaterials and products. The message is clear: mandatory nanotoxicology testing is inevitable. Those who produce, use, or test nanomaterials had better position themselves now for toxicity testing, or they may find themselves scrambling to catch up when the first wave of regulations hits the industry.
How should toxicology testing laboratories prepare themselves to meet the increased demand for testing and the unique testing protocols coming down the pipeline? And what capabilities should nanomaterial producers and users expect when they are using contracted toxicology labs to assess hazards?
Because of their unique characteristics and behaviors, nanomaterials require testing approaches that are specific to them and, in many cases, still in development. Specifically, labs must be equipped to characterize nanomaterials in multiple media and to generate and control exposures.
Instruments Required for Nanomaterial Characterization
|Instrument||Assessment Purpose||During Exposure||Post-Exposure||Notes|
|Scanning mobility particle size analyzer||Particle size class distribution and concentration||X||Real-time measurements|
|Cascade micro-orifice uniform deposit impactor (MOUDI)||Time-averaged mass concentration by particle||X||Requires long sampling times to collect enough material on stages|
|Scanning or transmission electron microscopy with energy dispersive X-ray analysis||Direct observation of particle size, shape, agglomeration state and chemical composition.||X||Can be conducted with much fewer particles|
|Inductively coupled mass spectrometry||Mass concentrations for metals or metal oxides||X||Especially useful in liquid systems|
|High-performance liquid chromatography||Mass concentrations for carbon-based materials||X||Very high sensitivity|
|Dynamic light scattering, photo disc centrifugation, or size-exclusion chromatography||Particle size and agglomeration state||X||X||Especially useful in liquid systems|
|Wet-cell scanning electron microscopy||Direct observation of particle size, shape and agglomeration state||X||X||Critical for liquid system analysis|
Dealing with nanomaterials
Nanomaterial toxicity testing requires characterizing the material’s properties and accurately measuring doses to determine safe exposure levels. Nanomaterials, however, are more difficult to observe in native form, analyze, handle, and keep in their original form than other materials. Entirely different technologies are required to determine how much of a material exists in a tissue or exposure system. Toxicologists also must identify the characteristics of the material—its particle size, form, shape, and surface chemistry—because one or more of these properties may cause toxicity.
To measure dose and identify the characteristics of a nanomaterial during a safety study, samples must be taken in air or other media an analyzed both with real-time and post-exposure techniques. Real-time sampling collects information about mass, particle number, and particle size during exposure, so exposures can be adjusted to correct the dose as needed to match a target concentration. Post-exposure analyses of collected samples verify the correct dose, by determining the mass gravimetrically and providing necessary information on other characteristics of the particle, the size during and after exposure, and the chemical composition, shape, and surface chemistry.
Inhalation studies require reliable generation of nanomaterial aerosols with consistent shape, size, concentration, and chemical purity for periods of five hours per day to up to two years. Maintaining a constant size is important because particle size determines where and how much material deposits in the upper or lower airways. Nanoparticles are a particular challenge because their high surface area and diffusion rates cause rapid agglomeration, often causing them to “stick” to the walls of delivery lines during exposures.
Particle characteristics such as chemistry and morphology (as shown by different colors in the figure) can be determined through scanning electron microscopy with energy dispersive spectroscopy. Image: PNNL
The contract laboratory industry is investing in research to develop improved instruments and engineering approaches to generate nanomaterial aerosols with better control over material properties and purity. For example, Battelle’s Toxicology Northwest inhalation toxicology facility, Richland, Wash., has developed the capability to expose rodents to nanoscale spherical Buckminsterfullerene “buckyball” particles. BioReliance, Rockville, MD., is developing in vitro test systems for detecting genotoxicity of nanomaterials, which involves finding non-toxic solvents and surfactant systems for suspending particles and developing new analytical capabilities for characterizing materials in liquids. Global Lifescience Solutions, LLC, Ann Arbor, Mich., is expanding and validating its cellular and biochemical assays for application to nanomaterial toxicity assessment while making strategic purchases of analytical equipment and forming new partnerships with laboratories specializing in particle characterization.
More R&D is needed in other areas—such as methods for dermal-exposure studies and in vitro assays as well as ensuring the availability of well-characterized nanomaterials for testing and methods development.
While influencing the future of nanotoxicology, forward-looking contract toxicology laboratories also are expanding their capabilities now to face the impending demand. Happily, this expansion presents business opportunities for small and large organizations. Small contract research groups can form partnerships or contract with organizations that specialize in particle characterization, such as the Nanotechnology Characterization Laboratory of the National Cancer Institute, Frederick, MD., the Particle Characterization Laboratory, Novato, Calif., or one of the U.S. Dept. of Energy’s national laboratories. Equipped with these resources, the nanotoxicology industry will be better positioned to meet the testing requirements for the rapidly expanding array of nanomaterials-based products entering the market.
Published in R & D magazine: Vol. 50, No. 1, February, 2008, p.28-29.