Nanotechnology

Strategic Plan for NIOSH Nanotechnology Research: Filling the Knowledge Gaps

IV. Goals (Continued)

4.2 10 Critical Research Areas

NIOSH has comprehensively begun to address its NTRC strategic goals by identifying the knowledge necessary to step through the risk management process to protect workers and responsibly move nanotechnology forward. The NIOSH NTRC strategic goals are being addressed by identification of intermediate goals and performance measures in 10 critical research areas: (1) exposure assessment (2) toxicity and internal dose, (3) epidemiology and surveillance, (4) risk assessment, (5) measurement methods, (6), engineering controls and personal protective equipment (PPE), (7) fire and explosion safety, (8) recommendations and guidance, (9) communication and information, and (10) applications. Additionally, since the fourth strategic goal of enhancing global workplace safety and health through national and international collaborations on nanotechnology research and guidance cross-cuts all 10 critical research areas, intermediate goals were developed for this area. Section 4.3 lists the intermediate goals and performance measures for each of the NIOSH NTRC critical research areas and the global collaboration efforts.

NIOSH participates in the National Nanotechnology Initiative’s (NNI) “Strategy for Nanotechnology Environmental Health and Safety Research.” Figure 4 shows the alignment of the four NIOSH NTRC strategic goals and the 10 NTRC critical research areas with the NNI environmental health and safety (EHS) priority research needs (see Appendix F). Planned projects within each of the 10 NIOSH critical research areas may meet one or more of the four NIOSH Strategic Goals. A check mark () means that a goal is addressed by projects within the critical research area. Alpha-numerical identifications indicate alignment of the NIOSH critical research goals with the NNI EHS priority environmental health and safety areas.

Critical Research Areas
NIOSH NTRC Strategic Goals	Exposure Assessment2	Toxicity and Internal Dose	Epidemiology and Surveillance	Risk Assessment	Measurement Methods	Engineering Controls and PPE	Fire  & Explosion Safety	Recommendations & Guidance	Communication and Information	Applications
1. Determine if nanoparticles and nanomaterials pose risks for work-related injuries and illnesses	A1 A2 D1 D4 D5 E1 E2	A2 B1 B2 B3 B4 B5	D1 D2 D3 D4 E4	A2 B1 B2 D4 E3	A1 A2 A3 A4 A5 B2	D5	A2
2. Conduct research on applying nanotechnology to the prevention of work-related injuries and illnesses1
3. Promote healthy workplaces through interventions, recommendations, and capacity building	E2		E4	E3 E5	E1	E1		E1 E5	E1 E5
4. Enhance global workplace safety and health1

¹The NNI EHS plan does not address applications or global activities pertaining to environmental health and safety of nanomaterials. However the NIOSH efforts described herein are consistent with the overall NNI strategy which does identify international opportunities for collaboration.

²NIOSH is the lead agency for the NNI EHS Strategic area on human and environmental exposure assessment.

Figure 4. Alignment of Critical Research Areas with the four Strategic Goals of the NIOSH NTRC and the NNI EHS priority environmental health and safety areas

4.3 Intermediate Goals and Performance Measures

4.3.1 Exposure Assessment

Exposure assessment is a critical component in determining whether nanomaterials pose occupational safety or health risks. Therefore, it is necessary to conduct exposure assessments in the workplace to identify the ways that workers may be exposed to nanomaterials, the amount of exposure that may occur, and the frequency of potential exposure. Without workplace exposure data, it is difficult to accurately characterize the work environment, identify sources that are emitting nanomaterials, or estimate the amount of nanoparticle exposure that workers may receive. In addition, exposure data can be beneficial when making decisions concerning risk management or evaluating the effectiveness of engineering controls and work practices in reducing worker exposures.

Intermediate Goal 1.1 Fate of nanomaterials in the work environment. Determine the key factors influencing the generation, dispersion, deposition, and re-entrainment of nanomaterials in the workplace, including the role of mixed exposures.

Performance Measure 1.1 Support at least 12 research projects (field trips) over the next three years to assess the fate of nanomaterials in the work environment.

Intermediate Goal 1.2 Worker exposures. Quantitatively assess exposures to nanomaterials in the workplace including inhalation and dermal exposure. Determine how exposures differ by work task or process.

Performance Measure 1.2 Within three years develop a baseline worker exposure assessment that identifies how exposures differ by work task or process.

4.3.2 Toxicity and Internal Dose

NIOSH has studied in great detail the toxicity of incidental exposures to nanoparticles generated from processes involving combustion, welding, or diesel engines. However, less is known about nanoparticles that are intentionally produced (engineered) with diameters or structures smaller than 100 nanometers. Many uncertainties exist as to whether the unique properties of engineered nanomaterials pose occupational health risks. These uncertainties arise because of gaps in knowledge about the potential routes of exposure, movement of nanomaterials once they enter the body, and the interaction of the materials with the body’s biological systems. Results from existing studies in animals and humans on exposure to incidental nanoscale and respirable particles provide preliminary information upon which to develop a research strategy to assess the possible adverse health effects from exposures to engineered nanomaterials.

Intermediate Goal 2.1. Key factors and mechanisms. Systematically investigate the physical and chemical properties of particles that influence their toxicity (e.g., size, shape, surface area, solubility, chemical properties, and trace components). Evaluate acute and chronic effects in the lungs and in other organ systems and tissues. Determine rates of clearance of nanoparticles after pulmonary exposure and translocation to systemic organs; characterize systemic effects. Determine dermal response to exposure to skin and quantitative penetration of nanoparticles into skin. Determine the biological mechanisms for toxic effects (e.g., role of oxidant stress), including from mixed exposures, and how the key chemical and physical factors may influence these mechanisms. Determine if nanoparticles are genotoxic/carcinogenic.

Performance Measure 2.1. Determine the pulmonary response (dose dependence and time course) to single-walled carbon nanotubes (SWCNT) within the next two years and multi-walled carbon nanotubes (MWCNT) within the next three years. Determine the cardiovascular response to pulmonary exposure to SWCNT and ultrafine titanium dioxide within the next two years. Determine the pulmonary deposition and fate of SWCNT within the next two years and MWCNT and ultrafine titanium dioxide within the next three years. Determine the in vitro effects of SWCNT and metal oxide nanoparticles on skin cells within the next two years and the in vivo effects of topical exposure within the next three years. Determine the genotoxic and carcinogenic effects of SWCNT within the next four years. Determine the central nervous system effects of pulmonary exposure to nanoparticles within the next four years. Determine the pulmonary and systemic effects of other nanoparticles with the next five years. These results will elucidate toxicological mechanisms over the next five years.

Intermediate Goal 2.2. Predictive models for toxicity. Integrate mechanistic models (including animal models and in vitro screening tests) for assessing the potential toxicity of new nanomaterials and provide a basis for developing predictive algorithms for structure/function relationships and comparative toxicity analyses for risk assessment. Evaluate the relationship between in vitro and in vivo responses, the relevance of instillation or aspiration exposure to inhalation, and the relevance of animal studies to human response.

Performance Measure 2.2. Determine the role of oxidant-generating potential in bioactivity of metal oxide nanoparticles and carbon nanotubes over the next three years. Determine the role of shape (nanospheres vs. nanowires) in bioactivity over the next three years. Determine the role of carbon nanotube diameter and length in bioactivity over the next four years. Develop in vitro assays for oxidant generation, fibrogenic potential, and ability to cause endothelial dysfunction over the next four years. These results will address the development of predictive algorithms for toxicity over the next five years.

Intermediate Goal 2.3. Metrics of dose. Determine whether (1) particle number, surface area, or other measure of bioavailability or bioactivity is a more appropriate dose metric for toxicity than mass or (2) other measures of bioavailability may be useful (e.g., an integrated measure of retention, solubility, oxidant-generating potential, surface area, and binding reactivity for proteins/lipids).

Performance Measure 2.3. Determine the pulmonary response to exposure to fine vs. ultrafine particles using both mass and surface area as the dose metric. Determine the role of oxidant generation in the bioactivity of metal oxide nanoparticles and carbon nanotubes. These results will address issues of most appropriate dose metric over the next three years.

Intermediate Goal 2.4. Internal dose. Determine the fate, clearance, and persistence of nanomaterials in the body (i.e., pulmonary, lymphatics, blood/systemic, brain) including possible de-agglomeration of nanoparticle agglomerates into primary particles and translocation of nanomaterials from the lung to systemic organs.

Performance Measure 2.4. Develop methods to label carbon nanotubes and track their pulmonary deposition and fate (i.e., clearance, interstitialization, and translocation) with time post-exposure. Use chemical analysis to track the deposition and fate of metal oxide nanoparticles. These results will address issues of internal dose over the next five years.

Strategic Plan for NIOSH Nanotechnology Research:
IV. Goals	VI. Goals (continued II)