Characterization Methods of Manufactured Nanomaterials for EHS Studies

Transcription

1 Characterization Methods of Manufactured Nanomaterials for EHS Studies Steven W Brown, MS, CIH International Standards Organization Technical Committee #229 on Nanotechnologies Convener Work Group #3 Environmental Health and Safety Nanotechnology holds great promise for creating new materials with enhanced properties and attributes. The unique properties of these various types of intentionally produced nanomaterials enable applications in commercial, medical, military and environmental sectors. Nanoparticles are present in the environment from both natural and anthropogenic sources. Examples of natural nanoparticles include volcanic ash, ocean spray, bacteria, forest fire smoke, mineral composites and clouds. Anthropogenic nanoparticles can be either incidental or engineered. Examples of incidental nanoparticles include combustion products, cookinggenerated aerosols, sandblasting emissions, mining emissions, metal working emissions and biomaterial degradation. Examples of engineered or nanoparticles created for specific purposes include carbon nanotubes, quantum dots, sunscreen pigments and fullerenes. Engineered nanoparticles have great diversity in shape and function, as seen in the large variety of carbon nanotubes, polymers, fullerenes, nanoribbons and dendrimers. Many nanoparticles have unique properties, such as being optically transparent and distinctive surface properties. Nanoparticles that are less then 5 nm have half of their atoms on the surface. Some nanoparticles have high surface energies that enable novel chemistry which is not evident in the bulk material of the same chemical composition. Some of the same special properties that make nanomaterials useful are also properties that may cause some nanomaterials to pose hazards to humans or the environment. There is a concern that some engineered nanoscale particles are in the size range of biological molecules, such as proteins and intracellular constituents that are critical to cellular functions, and thus have the potential to disrupt critical biological processes. Initial toxicology studies demonstrated pulmonary toxicology of single walled nanotubes in mice/rats, neural effects in fish exposed to fullerenes and cellular uptake of quantum dots. Studies of nanoparticle inhalation toxicology indicate that nanoparticles have high deposition efficiency throughout the respiratory tract, exhibit translocation to extrapulmonary organs and demonstrate variable toxicity in the respiratory tract, from highly toxic to benign. Nanoparticle size, chemistry and specific surface area are important parameters that influence toxicity. Nanoparticles have been shown to exacerbate asthma and other existing pulmonary disease states. In general, the smaller the particle size and greater the surface area, the more evidence of inflammation is detected. Nanoparticles with decreased pulmonary clearance are more prone to bioacculmulate and persist in the lung tissues.

2 There remain important nanomaterial toxicology questions, such as the effects of nanoscale features on exposure, pharmaco / toxicokinetic processes, receptor or membrane interactions and environmental chemistry and fate. Nanoparticles have unique characteristics due to their small size that influence toxicological effects. For the equivalent mass of a material, the particle count increases by 16 million when moving from 2 um to 100 nm particles. Nanoparticles exhibit different mobility mechanisms and move more like a fume or gas than other aerosols. Some nanoparticles exhibit selective uptake through cell membranes, which increases potential for toxic responses within the cellular organelles. An important first step in assessing the toxicity and exposure risk of any nanomaterial is to correctly identify and characterize the material. The diversity and complexity of nanomaterials makes chemical identification and characterization not only more important but also more difficult (single chemical component with spherical shape verses complex functionalized shape with large reactive surface area). There are existing analytical methods to assess occupational exposures to hazardous materials, environmental impact of a material release into the environment, product risk assessment/safety evaluations and transportation risk, however it is unknown if these methods can be accurately applied to nanomaterials. Key questions related to development of metrology techniques for nanomaterials include the following: Are current analytical methods applicable to nanomaterials? Is this issue relevant/common to one or more classes of nanomaterials? Can revisions to current analytical techniques be used or do new methods need to be developed? If a new method is needed can it be derived from an already existing method? New metrology methods are needed in order to fully characterize nanoparticles, perform accurate toxicological testing, monitor occupational exposures to nanomaterials, evaluate environmental toxicity, determine environmental fate, conduct product safety evaluations and perform Life Cycle Analysis of nanomaterials. Existing toxicological test methods need to be reviewed to determine if they are valid for nanoparticle testing or if they need to be modified to account for the differences between nanoparticles and larger size particles. Accurate toxicological assessments require many types of metrology and analytical techniques for the specific nanoparticle being assessed. In order to determine the relative toxicity and hazard of a specific nanomaterial, it is critical that, at a minimum, the administered dose and the received dose are known. Due to the small size and variations in surface properties, new analytic techniques are needed to determine nanoparticle dosage. These new methods include the ability to determine concentration of nanoparticles in various test media, standardized aerosol generation techniques, real time concentration instrumentation, analytical instrument calibration methods and particle size standards to validate instrument performance Adsorption, Distribution, Metabolism & Excretion (ADME) Toxicological Studies are performed in order to determine how a substance enters an organism, organs and cells, is distributed within an organism, organs and cells, is metabolized by the organism, impacts critical metabolic pathways and is excreted or stored by the organism. ADME testing results

3 provides pharmaco kinetics information on substances and provides insight into the potential toxicity of a material. The ADME testing of nanoparticles will require new analytical techniques to determine nanoparticle concentrations and size distributions in various test media, including individual cells, cell components, organs and biological tissues. The detection and quantification of the nanoparticles within biological systems will be extremely difficult and require analytical limits of detection that are not currently available. Measurement of nanoparticles is critical to ensure the safe processing and handling of nanomaterials in occupational settings. New measurement techniques are needed to evaluate the effectiveness of engineering containment controls designed to prevent the release of nanoparticles into the workplace and to measure potential employee exposure levels to nanomaterials. Traditional exposure assessment methods are ineffective for nanomaterials, as they typically rely on the collection of air samples and the measurement of the total mass of airborne particles (micron size materials) compared to a mass based exposure limit. Mass based exposure limits may not be applicable to nanomaterials where other factors, such a particle count or surface area, may be better indicators of materials toxicity. The monitoring of occupational exposures to nanoparticles will require new instruments for such functions as size-fractionated aerosol sampling, real-time aerosol sampling, surface area measurements, particle number concentration measurements, surface area estimation and surface contamination measurements. New instrument calibration techniques will also be needed. Existing environmental toxicity testing methods need to be reviewed, and potentially modified, for the testing of nanomaterials. The following water quality test methods should be evaluated: total suspended solids, total dissolved solids, ph, chemical oxygen demand and biological oxygen demand. The existing invertebrate and vertebrate aquatic toxicity tests will also need to be evaluated for applicability to nanomaterial testing. In order to determine the effects of the release of nanomaterials into the environment, new nanoparticle analytical techniques are needed for water, soil and air, as well as to determine environmental fate and transport mechanisms. Nanoparticles are being incorporated into a multitude of consumer products. The nanoparticles are typically bound in a matrix which prevents their release and potential for consumer contact. New metrology techniques are needed to assess the potential for nanoparticles to be released from products during normal use, unintended use and ultimate product disposal. Metrology Needs for Product Safety Evaluations includes the need to perform Product Life Cycle Analysis (LCA). Life Cycle Analysis is conducted on new products to determine potential safety and environmental stewardship issues. New metrology techniques are needed to assess the potential for nanoparticles to be released during product manufacturing, product use including unintended use and product disposal. LCA will require determination of biodegradation and biotransformation of nanomaterials when released into the environment. The International Standards Organization Technical Committee 229 on Nanotechnology is developing standards in three different work groups, Nomenclature, Metrology and Environmental Health Safety. The Environmental Health and Safety work group is currently

4 working on 5 approved work items on nanotechnology (see Table 1) including Health and safety practices in occupational settings, Endotoxin test on nanomaterial samples for in vitro testing, Generation of nanoparticles for inhalation toxicity testing, Characterization of nanoparticles for exposure chambers for inhalation toxicity testing and Material Characterization for toxicity testing. In addition to the approved New Work Items the work group has identified additional potential new work items including the development of ISO standards in support of the OECD Working Party on Manufactured Nanomaterials. The material characterization for toxicity testing work project is evaluating 47 existing material characterization methodologies to determine which characteristics will provide an indication of the toxicity of nanomaterials (see Table 2). Upon identification of the relevant material characteristic, assistance from TC#229 Work Group #2 on Metrology will be requested to further develop analytical techniques into an ISO standard.

5 Table 1. ISO TC229 Nanotechnologies Work Group #3 Roadmap and Project Timelines 1H H H H 2009 ISO TC 229 WG# 3 Environmental Health & Safety Standard Methods for Controlling Occupational Exposures to Nanomaterials Health and safety practices in occupational settings Occupational Standard for Handling Nanomaterials Standard Methods for Determining Relative Toxicity/Hazard Potential of Nanomaterials Endotoxin test on nanomaterial samples for in vitro testing Generation of nanoparticles for inhalation toxicity testing Characterization of nanoparticles for exposure chambers for inhalation toxicity testing Material Characterization for Toxicity testing Standard Methods for Toxicological Screening of Nanomaterials Standard method for sample preparation for in-vitro toxicity testing Nanomaterial specific toxicity screening test Standard Methods for Environmentally Sound Use of Nanomaterials Environmental Fate & Transport determination test methods Ecotoxicity testing methodologies Standard Methods for ensuring Product Safety of nanomaterial products Life cycle assessment of nanomaterial containing products Standard method to determine nanoparticle generation rate from products containing nanomaterials Standard Methods to support OECD Working Party on Manufactured Nanomaterials To Be Determined KEY Approved New Work Items In Progress are highlighted in light grey Potential New Work Items are highlighted in italics and dark grey

6 Table 2. Absolute Length Hydrophobicity Explosive Properties ph Volatilization of water and soil Redox photochemical reaction Particle size / distribution Partition coefficient n-octanol/water Agglomeration state / physicochemical structure Stimulus-Associated Photocatalytic Activity Aggregation Behavior Bio-persistence Length Flammability Physical State Unique properties related to nanosize Radical Formation Potential Particle Aerosol Generation State of the substance at 20 C and kpa Prior storage of material Surface Characteristics Dustiness Particles per Unit Mass Charge Crystallite Size Particle size Surface area Composition Diffusion Crystalline Phase Catalytic Properties Concentration Dissociation constant Boiling Point Crystal structure Topology Relative Density Redox Potential Purity Absorption property Manufacturing Process Dissociation Constant Zeta Potential Vapor Pressure Weight Wet / Dry transport