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NIOSH Safety and Health Topic:Nanotechnology |
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Strategic Plan for NIOSH Nanotechnology Research: Filling the Knowledge Gaps
Appendix D. NIOSH Extramural Research Nanotechnology Portfolio Summary FY 2001-2008BackgroundThe NIOSH Office of Extramural Programs (OEP) manages the competitive process for awarding occupational safety and health grants and cooperative agreements to the research community outside the Institute. This process includes peer review, program relevance, and priorities from the National Occupational Research Agenda (NORA), the NIOSH r2p initiative, congressional mandates, and sector, cross-sector or coordinated emphasis areas of the NIOSH Program Portfolio (http://www.cdc.gov/niosh/programs). From 2001-2008 to date, the Office of Extramural Programs (OEP) has funded nanotechnology research through Occupational Safety and Health Research Program Announcements (R01) and Small Business Innovation Research Grants (R43/44). Since FY-05, OEP has also participated in two joint Requests for Applications (RFAs) for Nanotechnology Research Grants Investigating Environmental and Human Health Issues. The US Environmental Protection Agency’s National Center for Environmental Research (NCER) and the National Science Foundation (NSF) participated in FY-05. The National Institute of Environmental Health Sciences (NIEHS) joined in FY-06. Funding was available to support Research (R01) grants for three years and Exploratory (R21) grants for two years. In FY-07, NIOSH/OEP participated in RFA-ES-06-008 Manufactured Nanomaterials: Physico-chemical Principles of Biocompatibility and Toxicity. This RFA was jointly sponsored by NIEHS, EPA and NIOSH. In FY-08, nanotechnology related research proposals submitted to standing program announcements are being considered for funding by NIOSH/OEP. PurposeExtramural funding of nanotechnology-related research has been undertaken to help increase the knowledge of nanotechnology and manufactured nanomaterials as they relate to occupational safety and health. Research areas supported by NIOSH/OEP include: assessment methods for nanoparticles in the workplace, toxicology of manufactured nanomaterials, and use of nanotechnology for improved workplace monitoring. Extramural nanotechnology research is important to NIOSH because it adds to the overall development of new information and complement efforts undertaken within the Institute. Status/ProgressFrom FY-01 to FY-04, OEP funded three R43/44 projects for a total funding commitment of about $950K (Table D-1). In FY-05, OEP began participating RFAs for Nanotechnology Research Grants Investigating Environmental and Human Health Issues. For the first RFA, 83 applications were received and 19 were recommended for funding. Fourteen of these met NIOSH criteria for relevance to occupational safety and health. Five of these were in the competitive range for funding consideration and two were funded by NIOSH. In FY-05, EPA funded 14 projects and NSF funded two projects under this RFA. NIOSH also funded one nanotechnology research grant through the R01 Program Announcement in FY-05 (Table 1). In FY-06, 81 applications were received in response to the RFA and 29 of these were recommended for funding. Six of these met NIOSH criteria for relevance and three of these were in the competitive range for funding consideration. NIOSH was able to fund one of these (Table 1). EPA funded 21 projects, NSF funded four and NIEHS funded three projects under this RFA. In FY-06, NIOSH also funded two Small Business Innovative Research grants on nanotechnology. In FY-07, a career development grant involving research on personal exposure to nanoparticles was funded. This is a three year project at the University of Iowa. To date in FY-08, NIOSH has funded a grant from the joint RFA on Manufactured Nanomaterials (Physico-chemical Principles of Biocompatibility and Toxicity). This project will be conducted at the University of Iowa. During the remainder of FY-08, nanotechnology related research proposals submitted to standing program announcements will be considered for funding by NIOSH/OEP. It is anticipated that at least two additional nanotechnology-related projects will be funded in FY-2008. Summaries of the projects funded by NIOSH/OEP are included as part of this extramural portfolio update. Contact information for the principal investigators of the projects funded by NIOSH/OEP is provided in Table 2 to encourage collaborative scientific efforts among researchers. To date, NIOSH/OEP has committed about $5.3 million dollars to research on applications and implications of nanotechnology. NIOSH/OEP plans to continue collaborative efforts with EPA/NCER, NSF, NIH/NIEHS, and other international agencies to support nanotechnology research with occupational safety and health implications. OEP will continue to confer with the NIOSH Nanotechnology Research Center regarding issues, gaps, and future directions. Additional InformationExtramural investigators interested in pursuing nanotechnology studies related to occupational health and safety can learn more about the interests of NIOSH in this area by visiting the following web pages: http://www.cdc.gov/niosh/topics/nanotech/ http://www.cdc.gov/niosh/topics/nanotech/research.html http://www2a.cdc.gov/niosh-nil/
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Extramural Nanotechnology Research Project SummariesThe project summaries included here contain the publicly available information from the NIH CRISP database (http://crisp.cit.nih.gov/). For additional information, please contact the Office of Extramural Programs. Investigator contact information is provided in Table 2 to encourage collaborative scientific efforts between researchers. Contact information for Dr. Hooker was not available. HOOKER 7471 (R43), WILLIAMS 7471 (R44)Novel Hydrogen Sulfide Sensors for Portable MonitorsThe primary objective for this project is the design, development, and demonstration of better sensor technology for the detection of hydrogen sulfide. Hydrogen sulfide is a highly toxic, colorless, flammable gas that reacts with enzymes that inhibit cell respiration. At high concentrations, hydrogen sulfide can literally shut off the lungs, while lower levels can burn the respiratory tract and cause eye irritation. This gas is encountered in a wide range of industries, and a number of standards have been established for occupational exposure. The OSHA Permissible Exposure Limit (PEL) is 10 ppm, the Short Term Exposure Limit (STEL) is 15 ppm, and exposures of 300 ppm or greater are considered immediately dangerous to life and health (IDLH). Because of the potential for adverse health effects at low concentrations, the industrial hygiene community is continually seeking improved performance from hydrogen sulfide sensors. Specific requirements include reliable and accurate detection in real time, quantitative measurement capabilities, low purchase and life cycle costs, and low power consumption (for portability). Sensors meeting these requirements will find numerous applications within the health and safety field. In addition, there are several potential spin-off opportunities in leak detection, emission monitoring, and process control. We will utilize alternative ceramic oxide materials, and a unique multi-layer fabrication process to accomplish the objectives of this project. The work plan includes optimization of the sensor materials, sensor element fabrication, sensor element packaging, in-house and external evaluation of the sensors, and establishing the foundation for new instrument development. The ultimate aim is a low-cost, low-power sensor that can be used in a new type of personal monitor. The envisioned monitor is a low profile, credit card sized "smart-card" that can not only alert the wearer when unsafe concentrations have been encountered but also to track cumulative individual worker exposure to a particular toxic gas species. ProgressThe early portions of this project focused on developing nano-structured sensor materials and morphologies targeted toward chemiresistive-based sensors. This work resulted in a commercial sensor which is being incorporated into the fixed-system H2S detection products of multiple partnering instrument manufacturers. The middle portion of the project focused on developing solid-state electrochemical sensors utilizing micro and nano-sized morphologies and structures. This has resulted in a working sensor currently being incorporated into an inexpensive, portable personal monitor as described above. Development of this monitor is wrapping up as the project is coming to an end during September 2006. RAJAGOPALAN (7963) From Nanoparticles to Novel Protective GarmentsThe overall objectives of this collaborative Phase I research between NanoScale and Gentex Corp. are (1) to investigate the use of highly adsorbent and reactive nanoparticles in protective garments and (2) to create and test new materials for use in the production of protective clothing. During routine chemical use, it is not always apparent when exposure occurs. Many chemicals pose invisible hazards and offer no warnings. More importantly, terrorists and saboteurs use a variety of toxic industrial chemicals to create improvised explosives, chemical agents and poisons. When dealing with hazardous materials released either by accident or intentionally, protective clothing is critical in guarding against the effects of toxic or corrosive products that could enter the body by inhalation or skin absorption and cause adverse effects. This project seeks to (a) establish the feasibility of incorporating highly adsorbent and reactive nanoparticles into lightweight, permeable textiles and (b) evaluate the utility of the resultant fabric as protective clothing using standard industry testing procedures. These novel protective garments will be tailored specifically toward personnel associated with federal, state or local emergency agencies as well as fire fighters and civilian first responders. To achieve the overall objective, reactivity of selected nanoparticle formulations to various toxic industrial chemicals will be explored by use of a quartz spring balance to determine sorptive capacity. Based on the outcome of this research, a single reactive nanoparticle formulation will be chosen for use in fabrics. The selected nanoparticle formulation will then be incorporated into suitable fabrics using two established techniques. Next, fabric test swatches will be evaluated for a number of criteria using industry recognized ASTM test methods. Finally, the top four nanoparticle embedded fabrics will be tested for physical and chemical resistance against two representative toxic chemicals using a standard ASTM procedure. KAGAN (8282) Lung Oxidative Stress/Inflammation by Carbon NanotubesBackgroundSpecific Aim 1 is to establish the extent to which SWCNT alone are pro-inflammatory to lung cells and tissue and characterize the role of iron in these effects using genetically manipulated cells and animals as well as antioxidant interventions. Specific Aim 2 is to determine the potential for SWCNT and microbial stimuli to synergistically interact to promote macrophage activation, oxidative stress, and lung inflammation. Specific Aim 3 is to reveal the extent to which SWCNT are effective in inducing apoptosis and whether apoptotic cells exert their macrophage-dependent anti-inflammatory potential during in vitro and in vivo SWCNT exposure. The project involves a team of interdisciplinary scientists with expertise in redox chemistry/biochemistry, cell and molecular biology of inflammation and its interactions with microbial agents, pulmonary toxicology of nanoparticles. ProgressTwo types of single walled carbon nanotubes were used (iron-rich and iron-stripped) to study their interactions with RAW 264.7 macrophages. Following ultrasonication of the SWCNT to separate strands, neither types were able to generate intracellular production of superoxide radicals or nitric oxide macrophages observed by flow-cytometry and fluorescence microscopy. SWCNT with different iron content displayed different redox activity in a cell-free model system. In the presence of microbial (zymosan) stimulated macrophages, non-purified iron-rich SWCNT were more effective in generating hydroxyl radicals than purified SWCNT. The presence of iron in SWCNT may be important in determining redox-dependent responses of macrophages. Dose and time-dependence studies of inflammatory responses in mice using pharyngeal aspiration of SWCNT demonstrated that SWCNT elicited unusual pulmonary effects in C57BL/6 mice that combined a robust but acute inflammation with early onset yet progressive fibrosis and granulomas. It was demonstrated occupationally relevant dose-dependent affects of SWCNT may exert toxic effects in the lung of exposed animals in vivo. SWCNT induced inflammation and exposure caused altered pulmonary function and microbial stimulation and clearance from the lungs of CWCNT exposed mice was compromised. An unusual and robust inflammatory and fibrogenic response was correlated with the progression of oxidative stress and apoptotic signaling. Not only are toxic effects of SWCNT important to consider but also the role of transitional metals, particularly iron should be investigated. O’SHAUGHNESSY (8806) Assessment Methods for Nanoparticles in the WorkplaceBackgroundPrimary objectives are to provide the scientific community and practicing industrial hygienists with verified instruments and methods for accurately accessing airborne levels of nanoparticles, and to assess the efficacy of respirator use for controlling nanoparticle exposures. We will satisfy these objectives through a combination of laboratory and field-based studies centered on the following specific aims: identify and evaluate methods to measure airborne nanoparticle concentrations; characterize nanoparticles using a complementary suite of techniques to assess their surface and bulk physical and chemical properties; and determine the collection efficiency of commonly-used respirator filters when challenged with nanoparticles. ProgressSeveral methods were used to aerosolize nanoparticles from bulk powders in the laboratory. An apparatus was developed to inject the aerosol into a mainflow of dry, filtered air through a charged neutralizing device. The amount and size distribution of the aerosol in the chamber is sampled with a scanning mobility particle sizer, samples from the chamber are also being analyzed by TEM. While the primary particle size of these powders average 20nm, an aerosol with a median size of 120 is generated. These findings have significance in occupational settings since agglomeration of the particles in this size range will have consequences in pulmonary deposition and respirator filtration. Nanosized particles were also found as contaminants in the water used. A variety of instruments are being compared for use in the field studies of nanoparticle exposure levels in two facilities, one in MN and one in TX. XIONG (8807) Monitoring and Characterizing Airborne Carbon Nanotube ParticlesBackgroundThe proposed research will develop a comprehensive, yet practical, method for sampling, quantification and characterization of carbon nanotube (CNT) particles in air. This method will be capable of classifying sampled particles into three categories: tubes, ropes (bundles of single-walled CNTs bounded by Van der Waals attraction force), and non-tubular particles (soot, metal catalysts, and dust, etc.), and measuring the number concentrations and size distributions for each type, and the shape characters (diameter, length, aspect ratio and curvature) of CNTs. The method will utilize available instrumentation to build an air monitoring system that is capable of sampling and sizing airborne CNT particles in a wide size range by using a 10-stage Micro-orifice uniform Deposit Impactor (MOUDI) and an Integrated Diffusion Battery previously developed in this laboratory. CNTs in workplaces; and a practical method using Atomic Force Microscopy image analysis technology to classify sampled CNT particles by type, and quantifying and characterizing each type separately. These methods are needed to determine potential health risks that may result from worker exposure to the various types: CNTs, nanoropes, and non-tubular nanoparticles. The results will also provide a foundation for field and personal sampling devices for CNTs. ProgressInstrumentation and materials are essentially ready. Years 2 and 3 will focus on method development for sampling, quantifying and characterizing airborne CNT aerosol particles. THOMPSON (8739) Antistatic Paint with Silent DischargeLong term ObjectivesProposed is an anti-static paint which can be used to alleviate danger from fires and explosions that are initiated by static discharge. The innovation for the proposed paint lies in its discharge mechanism which doesn't require grounding or hydration like other products that are currently on the market. Paint can be sprayed onto surfaces of clothing or equipment resulting in a lower capacitance or ability to build up charge on the material. Research DesignA series of formulations will be synthesized and tested on both metallic and plastic substrates. Relevance to Public HealthDevelopment of the antistatic paint will lead to immediate safety improvements for persons that work with volatile solvents in the fuel, coatings, and plastic industries as well as emergency responders in haz-mat situations. The paint could be useful for protecting the general public from electrostatic initiated explosions at the gas-pump or from uncomfortable static shock. In addition, this paint could lead to substantial savings in the electronics industry, where electrostatic discharge (ESD) events cost millions of dollars each year, due to lost products. DEININGER (8939) New Nanostructured Sensor Arrays for Hydride DetectionBackgroundThe goal of the proposed project is to develop improved sensors for the detection of hydrides (including arsine, phosphine and diborane) for protection of worker health and safety. Current sensors suffer from severe limitations including lack of selectivity, and limited accuracy and lifetime. An electronic sensor system, capable of automatically warning workers of the presence of one of these toxic gases, would provide a substantial benefit for worker health and safety. This project will take advantage of advances in nanotechnology, ceramic micromachining and materials chemistry to create sensors that are substantially better than current state of the art. These improved sensors will be the basis for improved personal and permanent monitors for increased protection of workers in the semiconductor industry. DUTTA (9141) Role of Surface Chemistry in the Toxicological Properties of Manufactured NanoparticlesBackgroundThe objectives of this program are to verify two hypotheses. First, the quantifiable differences in surface reactivity of nanoparticles, as measured by acidity, redox chemistry, metal ion binding and Fenton chemistry as compared to micron-sized particles of similar composition cannot be explained by the increase in surface area alone. Second, the oxidative stress and inflammatory response induced by nanoparticles upon interaction with macrophages and epithelial cells is dependent on their surface reactivity. The basis of these hypotheses is that nanoparticles contain significantly higher number of “broken” bonds on the surface that provide different reactivity as compared to larger particles. The experimental approach focuses on three classes of manufactured nanoparticles, catalysts (aluminosilicates), titania and carbon. For the catalysts and titania samples, nanoparticles (< 100 nm) and micron-sized particles of similar bulk composition will be studied. For carbon, carbon black and single walled carbon nanotubes are chosen. Nanoparticles of aluminosilicates and titania will be synthesized, whereas the other particles will be obtained from commercial sources. Characterization will involve electron microscopy, surface area, surface and bulk composition. Reactivity of well-characterized particles in regards to their acidity, reaction with antioxidants simulating the lung lining fluid, coordination of iron and Fenton chemistry will be carried out using spectroscopic methods. Particular attention will be paid to surface activation as may exist during manufacturing and processing. In-vitro oxidative stress and inflammatory responses upon phagocytosis of the particles by macrophages and pulmonary epithelial cells will form the toxicological/biological end points of the study. Methods include gene array techniques, assays for reactive oxygen species and adhesion molecules on endothelial cells. PETERS (9255) Personal Exposure Monitoring to Engineered NanoparticlesWorldwide production of engineered nanoparticles is expected to grow from 2,000 metric tons to 50,000 metric tons over the next decade. New industrial processes must be introduced into the workplace to accommodate this growth. Although studies have shown some nanoparticles to be toxic, methods to assess personal exposure do not exist. Knowledge of personal exposure may be particularly important for such small particles because their concentration tends to decay rapidly with distance from a source. Dr. Peters will conduct laboratory studies to evaluate the precision and accuracy of methods developed by his research group to assess personal exposure to nanoparticles. These methods will then be used to investigate the extent to which workers are exposed to engineered nanoparticles in a facility that produces and handles them. Mixed models will be used to identify the determinants of exposure, while controlling for the between-worker (spatial) and within-worker (temporal) variability. Computer controlled electron microscopy with energy dispersive X-ray detection will be used to further characterize the samples collected in the field study by size, composition, and morphology. These data will be used to apportion exposures to sources. The research proposed in this application is significant because it will enable direct assessment of personal exposure to nanoparticles on time scales relevant to potential acute and chronic adverse health outcomes. As an outcome of these studies, an understanding of exposures will help to prioritize studies in toxicology, epidemiology, and engineering controls to better protect workers. The research component will be complemented by a vigorous career development plan, which will include: (1) formal training in responsible conduct of research, epidemiology, and electron microscopy; (2) regular meetings with the sponsors of this award; (3) participating in group meetings and departmental seminars; (4) presenting results at scientific meetings; and (5) publishing results in peer-reviewed journals. The multidisciplinary team of sponsors will play an active role in both the research and career development component of this award. GRASSIAN (9448) An Integrated Approach Toward Understanding the Toxicity of Inhaled NanomaterialsManufactured nanomaterials are found in cosmetics, lotions, coatings, and used in environmental remediation applications. There exists a large opportunity for exposure through many different routes making it necessary to study the health implications of these materials. The primary objective of this research is to fully integrate studies of the physical and chemical properties of commercially manufactured nanoparticles with inhalation toxicological studies of these same nanoparticles to determine those properties that most significantly affect nanoparticle toxicity. Our central hypothesis is that nanoparticle physico-chemical properties differ widely among particle types and certain properties induce adverse health outcomes. Furthermore, we hypothesize that nanoparticle toxicity is influenced by the susceptibility of the individual as well as the presence of other inflammatory substances. We will address these hypotheses through a series of specific study aims designed to establish a relationship between nanoparticle physicochemical properties and health outcomes. Specific Aim 1: Evaluate nanoparticle chemical composition (bulk and surface) on nanoparticle toxicity in acute and sub-acute exposure studies. Experiments will be designed to investigate nanoparticle composition (bulk and surface) before, during and after inhalation exposure studies. Specific Aim 2: Determine the impact of nanoparticle physical morphology (agglomeration size, agglomeration state and nanoparticle shape) on nanoparticle toxicity. Incorporate animal inhalation studies to determine the relationship between nanoparticle agglomerate size and nanoparticle shape on toxicity. Specific Aim 3: Determine if pulmonary clearance is impaired by inhaled nanoparticles and if impaired clearance increases the risk of pulmonary infection. The pulmonary clearance mechanism, especially the ability of alveolar macrophages to clear microbes or foreign particles, can be impaired by inhaled particulates. Compare lung clearance rates after inhalation of nanoparticles of different composition. Specific Aim 4: Compare lung inflammation produced by co-exposure of nanoparticles with other inflammatory substances and relative to the nanoparticles alone. Evaluate synergistic effects with other common aerosols present in the indoor and outdoor environments including endotoxins and sulfate aerosols (e.g. ammonium sulfate).
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Appendix D
