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Strategic Plan for NIOSH Nanotechnology
Research: Filling the Knowledge Gaps
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Appendix G. Summary of Capabilities and Gaps for Nanotechnology Measurement Methods at NIOSH
Measurement Methods is a critical topic area in the NIOSH Nanotechnology Research Center (NTRC) Strategic Plan. This reflects the fact that effective and scientifically justified measurement methods are essential to understanding, predicting, and quantifying the chemical and physical properties and the behavior and toxicity of nanomaterials. The overarching Measurement Methods goals identified in the NTRC Strategic Plan are:
- Extend existing measurement methods. Evaluate current methods for measuring airborne mass concentrations of respirable particles in the workplace and determine whether these mass-based methods can be used as an interim approach for measuring nanomaterials in the workplace and to maintain continuity with historical methods.
- Develop new measurement methods. Expand the currently available instrumentation by devel-oping and field testing methods that can accurately measure workplace airborne exposure concen-trations of nanomaterials using metrics associated with toxicity (e.g., particle surface area).
- Validation of measurement methods. Develop testing and evaluation systems for compari-son and validation of sampling instruments and methods.
Meeting these goals supports success in the other nine critical topic areas of the NTRC Strategic Plan: Toxicity and Internal Dose, Risk Assessment, Epidemiology and Surveillance, Engineering Controls and Personal Protective Equipment, Exposure Assessment, Fire and Explosion Safety, Recommendations and Guidance, Communication and Education, and Applications.
In addition, the key components of the NTRC Strategic research plan have been incorporated into the five critical Environmental, Health and Safety (EHS) research areas identified by the Nanotechnology Environmental and Health Implications (NEHI) Working Group: Instrumentation, Metrology, and Analytical Methods; Nanomaterials and Human Health; Nanomaterials and the Environment; Health and Environmental Exposure Assessment; and Risk Management Methods.
Similar to NIOSH goals in the NTRC Strategic Plan, the NEHI goals in the research category of “Instrumentation, Metrology, and Analytical Methods” are:
- Develop methods to detect nanomaterials in biological matrices, the environment, and the workplace.
- Understand how chemical and physical modifications affect the properties of nanomaterials.
- Develop methods for standardizing assessment of particle size, size distribution, shape, struc-ture, and surface area.
- Develop certified reference materials for chemical and physical characterization of nanomate-rials.
- Develop methods to characterize a nanomaterial's spatio-chemical composition, purity, and heterogeneity.
Success in the Measurement Methods activities at NIOSH will foster success in overall national program. The following sections summarize NIOSH capabilities and critical gaps in Measurement Methods as they apply to the ten NTRC critical topic areas:
Toxicity and Internal Dose: NIOSH has developed and is using a suite of biological measurement techniques to assess mechanisms of damage and health endpoints such as oxidative stress, inflammation, and fibrosis (See attached Table G-1). The ability to relate those endpoints to physical and chemical properties of the administered nanoparticles cannot rely on simple measures such as particle mass. The recent purchase and installation of a field-emission electron microscope to the NIOSH HELD facility in Morgantown has improved the capability to image nanoparticles such as gold-labeled carbon nanotubes in biological tissues. I addition, this instrument is being used to determine the size of nanoparticles sampled from an aerosol or a suspension. Evaluations of the capabilities of the new microscope are underway, including examination of reference materials obtained in collaboration with NIST. NIOSH/HELD is also determining the size of nanoparticles in suspension using a Dynamic Light Scattering Analyzer. The NIOSH field team needs similar improvements their microscopy capabilities to characterize workplace aerosols. Completion of the purchase and delivery of a new TEM/STEM to the NIOSH DART laboratories in Cincinnati will provide an improve linkage between measurement studies for toxicity and measurement studies for field team and exposure assessment studies.
Development of a graded suite of nano-reference materials is needed to support improved understanding of the mechanisms of toxicity of mixed materials. NIOSH/HELD is studing well characterized SWCNT (NASA), MWCNT (Mitsui), SnO2 and TiO2 nanospheres and nanowires (WVU), and silicon nanowires (IBM). They are also working with NIST to obtain other nanoparticles types. Recent in vitro toxicity testing at NIOSH of a raw single-walled carbon nanotube material obtained from NIST has demonstrated the uncertainties associated with assessing toxicity of a “real-world” complex mixture material. The joint NIOSH-NIST-DOE certified reference material for 200-nm diameter primary particle size beryllium oxide will be issued in early 2008.
Risk Assessment: Because occupational exposure limits have not been, and are not soon expected to be developed for nanoscale particles and nanoparticle-containing materials, NIOSH is developing proactive guidance for risk assessment and risk management that incorporates successful pharmaceutical industry approaches to the use of performance-based occupational exposure limits. Current measurement gaps to bringing together the key risk assessment factors of risk identification, exposure assessment, dose-response relationships, and human dosimetry are two-fold: lack of real-time instruments that can discriminate nanomaterials of interest and lack of actual field measurements of actual workplace conditions. Progress is unlikely on the real-time discrimination front, but there is promise in NIOSH work on an improved method to discriminate between types of carbon materials. As noted in the toxicity section, evaluation of nanomaterial properties is likely to require retrospective analyses such as microscopy. In the risk assessment area, as well as for all critical areas in the NTRC strategic plan, the opportunity to develop and validate improved measurement methods will be ongoing.
Epidemiology and Surveillance: “Who is exposed to what” is the key measurement question for epidemiology and surveillance that may be filled in part by the NIOSH study of industrial exposures to nano-metal-oxides. Based on available technologies for measuring airborne nanoparticles, the metrics of exposure are currently limited to particle number concentration, and particle size distributions based on total particle mass or number, or retrospective analysis of collected material. This gap is not soon likely to be filled. Collecting and archiving airborne total and size-selected dust samples from representative workplaces may provide a resource for future analysis.
Engineering Controls and Personal Protective Equipment: Recent experimental confirmation at NIOSH and at other research centers that nanoparticles are efficiently collected on filter media by diffusion has filled a critical gap in the understanding area of respiratory protection. These studies were enabled by aerosol generation and measurement methods for nanoscale aerosols including silver and sodium chloride. Measurement methods are being developed to assess penetration of nanoparticles through protective clothing.
Exposure Assessment: The NIOSH nanotechnology field team protocol for baseline exposure assessment involves condensation particle counting, optical particle counting, and electron microscope for particles collected on 37-mm diameter filter cassettes (See Table G-2). This protocol is currently the state of the art. The expanded field team assessment protocol involves research-grade instruments that are larger in size, heavier in weight, more susceptible to damage, more expensive, and more labor-intensive. These include scanning mobility particle sizing, lung-deposited surface area sampling, and electrical and low-pressure cascade impaction. A challenging gap to be addressed my instrument manufacturers is to improve the portability of research grade instruments. A key gap that NIOSH can address is to determine the extent to which basic measurements and research measurements can be related.
Fire and Explosion Safety: The essential measurement methods gap for fire explosion safety is the need to assemble the currently available body of information about the state of the art for assessing fire and explosion safety, both for conventional materials and for nanomaterials. NIOSH can provide a valuable contribution by bringing this information together and making it accessible to the industrial hygiene community.
Recommendations and Guidance: The key measurement methods gaps for providing recommendations and guidance are the lack of validated tools to conduct a comprehensive set of risk assessment and risk management steps. The best that can currently be done is to establish an approach that can function with limited information, and grow with improved measurement methods in the future. The draft approach under development involves a combination of proactive qualitative risk assessment and control, performance-based occupational exposure limits, and verification of the efficacy of control.
Communication and Information: An alternate way to view measurement methods goes beyond measuring properties of nanomaterials and focuses on measuring the need for an effectiveness of communication and education for nanotechnology health and safety. One view of measuring effectiveness is that it can best be done in conjunction with existing safety initiatives that begin with the similarities of concerns for nanomaterials as a subset of chemical hazards in the workplace.
Applications: Although a number of nanotechnology-enabled improvements of occupational safety and health practice have been proposed, a critical gap is that few have been catalogued and critically evaluated. An example question is whether nanosilver impregnated filters actually involve nanoparticles, and whether such filters are actually more efficacious for collection and neutralization of bioaerosols than conventional filter media.
Table G- 1: Status Summary for the NIOSH Suite of Measurement Methods to Characterize the Biologically Relevant Properties of Nanoparticlesin Health Hazard Evaluations |
Parameters to be Measured |
Instrumentation, Method or Procedure for the Measurement |
Status at NIOSH / comments |
1. Generation of reactive species in vitro by the nanoparticles of interest |
a. Electron spin resonance (ESR) spectroscopy of nanoparticles suspended in phosphate-buffered saline plus H2O2.
b. ESR of lung or dermal cells exposed in vitro to nanoparticles.
c. Oxygen consumption, superoxide anion release, H2O2 production, or chemiluminescence from alveolar macrophages exposed in vitro to nanoparticles. |
Available and in use |
2. Cytotoxicity of nanoparticles in vitro |
a. Release of lactate dehydrogenase from cell exposed to nanoparticles in vitro
b. Oxidative metabolism (MMT assay) of cells exposed to nanoparticles in vitro. |
Available and in use |
3. Oxidant stress from exposures to nanoparticles in vitro |
a. Depletion of total antioxidants in cell exposed to nanoparticles in vitro.
b. Decrease of total thiols in cells exposed to nanoparticles in vitro.
c. Oxidative DNA damage in cells exposed to nanoparticles in vitro. |
Available and in use
|
4. In vivo exposure methods for controlled delivery of nanoparticles |
a. Intratracheal instillation of a suspension of nanoparticles. |
Available and in use
Agglomeration can result in non-uniform delivery of particles to the lung. Suspension of nanoparticles in alveolar lining fluid greatly improves delivery and increased the magnitude of pulmonary response. |
b. Pharyngeal aspiration of a suspension of nanoparticles. |
Available and in use
Provides less intrusive, more reproducible, and better characterized delivery efficiency than instillation
Is faster and more economical than inhalation
Suspension in alveolar lining fluid reduces nanoparticle clumping and improves the dispersion and delivery of individual nanoparticles |
c. Inhalation of an aerosol of nanoparticles. |
Available and in use for SWCNT, MWCNT, and ultrafine TiO2 |
d. Dermal application of a suspension of nanoparticles. |
Available and in use |
5. In vivo response to nanoparticles |
a. Pulmonary responses: cell damage (lavage LDH), air/blood barrier damage (lavage albumin), inflammation (lavage PMN, lavage cytokines, alveolitis by histopathology),
b. oxidant stress (lung antioxidant levels, lung lipid peroxidation), fibrosis (collagen staining histopathology).
c. fibrosis (collegen staining histopathy).
d. Cardiovascular responses: microvascular response to vasodilators, microvascular oxidant stress, adhesion of PMN to the microvessel wall, aortic oxidant stress (HO-1 production, oxidative, mitochondrial DNA damage), aortic plaque formation (histopathology).
e. Neuro responses: cytokine production in various regions of the brain, markers of blood/brain barrier damage.
f. Dermal responses: inflammation (histopathology), oxidant stress (lipid peroxidation, antioxidant depletion). |
Available and in use |
6. Translocation of nanoparticles |
a. Label nanoparticles with gold or quantum dots and track their movement to systemic organs by neutron activation or fluorescence, respectively. |
Available and in use.
Substantially enhanced by 2007-09 acquisition of the new field emission microscope
Addition of gold may alter nanoparticle characteristics
Not all nanoparticles can be labeled |
Table G-2: Summary of the Instruments and Nanoparticle Measurement Methods being used and evaluated in the NIOSH Nanotechnology Research Program |
Instrument or Method |
Purpose |
Status at NIOSH / Comments |
Condensation Particle Counter (CPC), TSI model 3007 |
Measures total particles in the 10 nm - 1000 nm range |
Used in nano field team baseline assessments
Cannot discriminate nanoparticles of interest from other airborne particles (This inherent problem applies to all air sampling instruments in this table.)
There is a general lack of validation of how this and other air sampling instruments respond to the full spectrum of nanoparticles that may be found in the workplace, including varieties of primary particles, agglomerates or aggregates, and other physical forms and varieties of chemical forms. A suite of nanoparticle reference materials are needed to perform the needed validations. |
Condensation Particle Counter (CPC) TSI Model 8525 P-Trak Ultrafine Particle Counter |
Measures total particles in the 20 nm – 1000 nm range through a hand-held probe that enables extractive sampling from ducts or enclosures |
Procured in October 2007 for use in nano field team baseline assessments
Enables extractive sampling from ducts or enclosures
Limitations include lack of definitive data on particle-size-dependent losses in the probe and sampling line |
Optical Particle Counter, ARTI model HHPC-6 |
Measures particles in the 300 nm – 50,000 nm range |
Used in nano field team baseline assessments
Enables assessment of agglomerates and aggregates of nanoparticles and larger diameter particles of nanostructured materials |
Indoor Air Quality Monitor, TSI Model Q-Trak Plus |
Provides ambient temperature, RH, CO2, and CO measurements |
Used in nano field team expanded assessments, or when it has been demonstrated that environmental conditions need to documented
Questions about the importance of environmental conditions are being addressed in the DRDS instrument chamber tests |
Optical Particle Counter, Grimm model 1108 |
Measures particles in the 300 nm – 20,000 nm range |
Used in nano field team expanded assessments |
Diffusion charger, Eco-Chem Analytics Model DC 2000-CE |
Measures active particle surface area up to 1000 nm particle diameter |
Used in nano field team expanded assessments |
Aerosol photometer, Dustrak model 8520 |
Measures particle mass from 300 nm to 2500 nm |
Used in nano field team expanded assessments
Could be used in the baseline studies |
Electrical Low Pressure Impactor (ELPI), Dekati |
Measures number of particles/size cut-point from 7 nm to 10000 nm in 12 stages |
Used in nano field team expanded assessments |
Scanning Mobility Particle Sizer, TSI model 3034 |
Measures number of particles as a function of mobility diameter in the range of 10 nm to 487 nm in 54 size channels |
Used in nano field team expanded assessments |
Airway deposited particle surface area analyzer, TSI Model 3550 |
Purports to estimate the surface area of particles deposited in the lung relative to ICRP standard reference man. |
Used in nano field team expanded assessments
Surface area measurements include more than the nanoparticles of interest.
Reported values are estimates of the external particle surface area, whereas total particle surface area (e.g., of all primary particles in agglomerate or aggregate clusters) may be the more biologically relevant metric. |
Wide-Range Particle Spectrometer, MSP Corp. |
Measures number of particles as a function of mobility diameter in the range of 10 nm to 10,000 nm |
Used in nano field team expanded assessments |
Micro-Orifice Uniform Deposit Impactor (MOUDI) sampler, MSP Corp. |
Collects particles in the range from 5 nm to 18000 nm as a function of aerodynamic diameter by cascade impaction on 12 or more stages plus a back up filter at a flow rate of 30 lpm. |
Used in nano field team expanded assessments |
Sioutas Cascade Impactor |
Collects particles in the range from 250 nm to 2500 nm as a function of aerodynamic diameter by cascade impaction on 4 stages (cut points of 2.5 um, 1.0 um, 0.5um , and 0.25) plus a back up filter at a flow rate of 9 lpm. This personal cascade impactor unit may be worn by a worker. |
Used in nano field team expanded assessments
Could be used in baseline assessments |
Point-to-plane electrostatic precipitator (ESP), InTox Products |
Collects particles on 3-mm-diameter grids for transmission electron microscopy (TEM). |
Used in nano field team expanded assessments
Has promise for routine inclusion in baseline assessments when NIOSH development of a rugged, hand-held version of the ESP is fully developed |
Impactor-based collection on TEM grid |
Collects particles on 3-mm grids mounted onto MOUDI substrates for TEM. |
Used in nano field team expanded assessments |
37-mm plastic cassette with mixed-cellulose-ester (MCE) filters |
Collects particles from the personal breathing zone of workers or from the general area for analytical chemistry or for scanning electron microscopy (SEM) or for TEM if the filter is clarified. |
Used in nano field team baseline assessments |
Cascade aerosol cyclone, SRI-type, InTox Products |
Collects particles as a function of aerodynamic diameter for particle size distribution and for subsequent evaluation of particle properties as a function of size |
Has been used in other NIOSH research programs (e.g., beryllium)
Could be used in nano field team expanded assessments |
Collection of bulk powder samples |
Collection of bulk process powder materials for retrospective physicochemical analyses, including microscopy, surface area analysis, density determination, etc. |
Used in nano field team expanded assessments
Occasionally used in intermediate assessment studies to allow access to a greater variety of feedstock materials than may be currently in use during a baseline assessment |
Helium gas pycnometry, Quantachrome Multipycnometer |
Measures the particle material density of bulk samples |
Used in nano field team expanded assessments |
Nitrogen adsorption specific surface area measurement, Quantasorb BET system |
Measures particle specific surface area of bulk samples |
Used in nano field team expanded assessments
Limitations include possible material alterations during sample heating to removed adsorbed water |
Strategic
Plan for NIOSH Nanotechnology Research: |
Appendix
F |
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Page last modified:
March 4, 2008
Page last reviewed:
March 4, 2008
Content Source: National Institute for Occupational Safety and Health (NIOSH)
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