Interim Guideline for Working Safely with Nanotechnology (Based on the Most Current NIOSH Information at 01-Sep-2005. This Interim guideline will be revised on completion of the National Nanotechnology Research Agenda and NIOSH Recommendations) What is Nanotechnology? Nanotechnology is somewhat loosely defined, although in general terms it covers engineered structures, devices and systems that have a length scale of 1 – 100 nanometers1. At these length scales, materials begin to exhibit unique properties that affect physical, chemical and biological behavior. Researching, developing and utilizing these properties is at the heart of the new technology. Nanotechnology is the understanding and control of matter at dimensions of roughly 1 to 100 nanometers, where unique phenomena enable novel applications1. A nanometer is one-billionth of a meter; a sheet of paper is about 100,000 nanometers thick. Encompassing nanoscale science, engineering and technology, nanotechnology involves imaging, measuring, modeling, and manipulating matter at this length scale. At this level, the physical, chemical, and biological properties of materials differ in fundamental and valuable ways from the properties of individual atoms and molecules or bulk matter. Nanotechnology R&D is directed toward understanding and creating improved materials, devices, and systems that exploit these new properties. Medical researchers work at the micro- and nano-scales to develop new drug delivery methods, therapeutics and pharmaceuticals. For instance, DNA, our genetic material, is in the 2.5 nanometer range, while red blood cells are approximately 2.5 micrometers1. Nanotechnology involves the creation and/or manipulation of materials at the nanometer (nm) scale either by scaling up from single groups of atoms or by refining or reducing bulk materials. A nanometer is 1 x 10-9 m or one millionth of a millimeter. To give a sense of this scale, a human hair is of the order of 10,000 to 50,000 nm, a single red blood cell has a diameter of around 5000 nm, viruses typically have a maximum dimension of 10 to 100 nm and a DNA molecule has a diameter of 2 – 12 nm1. The use of the term “nanotechnology” can be misleading since it is not a single technology or scientific discipline. Rather it is a multidisciplinary grouping of physical, chemical, biological, engineering, and electronic, processes, materials, applications and concepts in which the defining characteristic is one of size. Background The past decade has seen intense interest in developing technologies based on the unique behavior of nanometer-scale (nanoscale) structures, devices and systems, leading to the rapidly expanding and highly diverse field of nanotechnology. Interim Guideline for Working Safely with Nanotechnology Although many nanotechnologies are still in the pre-competitive stage, nanoscale materials are increasingly being used in optoelectronic, electronic, magnetic, medical imaging, drug delivery, cosmetic, catalytic and materials applications. Between 1997 and 2003, worldwide government investment in the field rose from $432 million a year to just under $3 billion a year, and the global impact of nanotechnology-related products is predicted to exceed $1 trillion by 20152. NIOSH is unaware of any comprehensive statistics on the number of people in the U.S. employed in all occupations or industries in which they might be exposed to engineered, nano-diameter particles in the production or use of nanomaterials. Perhaps because of the relative newness of the nanotechnology industry, there appear to be no current, comprehensive data from official survey sources, such as the U.S. Bureau of Labor Statistics (BLS). Occupational Health Risks Existing research shows there is little evidence to suggest that the exposure of workers arising from the production, handling, and processing of nanoparticles has been adequately assessed6. Current knowledge is inadequate for risk assessment purposes6. No information has been identified about worker exposures to nanoparticles in the university/research sector or in the new nanoparticle companies6. Occupational health risks associated with manufacturing and using nanomaterials are not yet clearly understood. The rapid growth of nanotechnology is leading to the development of new materials, devices and processes that lie far beyond our current understanding of environmental and human impact. Many nanomaterials and devices are formed from nanometer-scale particles (nanoparticles) that are initially produced as aerosols or colloidal suspensions. Exposure to these materials during manufacturing and use may occur through inhalation, dermal contact and ingestion. Minimal information is currently available on dominant exposure routes, potential exposure levels and material toxicity. What information does exist comes primarily from the study of ultrafine particles (typically defined as particles smaller than 100 nanometers). Studies have indicated that low solubility ultrafine particles are more toxic than larger particles on a mass for mass basis. There are strong indications that particle surface area and surface chemistry are primarily responsible for observed responses in cell cultures and animals. There are also indications that ultrafine particles can penetrate through the skin, or translocate from the respiratory system to other organs. Research is continuing to understand how these unique modes of biological interaction may lead to specific health effects. Workers within nanotechnology-related industries have the potential to be exposed to uniquely engineered materials with novel sizes, shapes and physical and chemical properties, at levels far exceeding ambient concentrations. To understand the impact of these exposures on health, and how best to devise appropriate exposure monitoring and Page 2 of 11 Interim Guideline for Working Safely with Nanotechnology control strategies, much research is still needed. Until a clearer picture emerges, the limited evidence available would suggest caution when potential exposures to nanoparticles may occur. NIOSH Activities A number of active research programs within NIOSH are investigating ultrafine and nanoparticle behavior, and the health risks associated with nanomaterials. A NIOSH Nanotechnology Research Center is being developed that will coordinate institute-wide nanotechnology-related activities. The Institute is also working with other agencies to address health issues associated with nanotechnology, including participation in the National Nanotechnology Initiative3 and the Nanoscale Science, Engineering and Technology subcommittee of the National Science and Technology Council committee on technology (NSET). Building on these initiatives, NIOSH is developing a strategic plan to address immediate and long-term issues associated with nanotechnology and occupational health in partnership with other federal agencies, research centers and industry. NIOSH, the Environmental Protection Agency, and the National Science Foundation are seeking applications proposing research about the potential implications of nanotechnology and manufactured nanomaterials on human health and the environment. Further information is available at http://es.epa.gov/ncer/rfa/2004/2004_manufactured_nano.html NIOSH’s key role in conducting and partnering in research on occupational exposures to nanomaterials is noted in a new strategic plan under the National Nanotechnology Initiative. The National Nanotechnology Initiative Strategic Plan: December 2004 charts the vision, goals, and plans by which NIOSH and partner agencies will work to expedite the responsible advancement of nanotechnology over the next 5 to 10 years, and to ensure that the U.S. will remain a world leader in nanotechnology research and development. The strategic plan is available at http://www.nano.gov/NNI_Strategic_Plan_2004.pdf The NIOSH Nanotechnology and Health & Safety Research Program. NIOSH is conducting a five-year multidisciplinary study into the toxicity and health risks associated with occupational nanoparticle exposure. Research will cover aerosol generation and characterization studies in the lab and in the field, toxicity studies investigating the significance of aerosol surface area as a dose metric, and cardiopulmonary toxicity and lung disease related to carbon nanotubes, and other nanoparticles. The Nanotechnology Safety and Health Research Program is coordinated by Vincent Castranova, Ph.D., who provided information and current recommendations for this Interim Guideline. Knowledge Gaps 1: The nanoparticle nomenclature is not sufficiently well described or Page 3 of 11 Interim Guideline for Working Safely with Nanotechnology agreed Currently there are no agreed definitions for nanoparticles, nanoparticle aerosols, or for the various types of nanoparticles which are produced. Definitions proposed need to define a size interval to take account of the distribution in sizes likely to be present, to consider whether the definition should be based on physical dimensions (e.g. length, diameter, surface area) or on some behavioral property such as diffusivity and take account of agglomerated aerosols. Progress on nomenclature issues is usually best achieved based on consensus. The planned conference on nanoparticle health risks (organized by HSE and NIOSH) will provide an ideal forum to discuss these issues. 2: There are no convenient methods by which exposures to nanoparticles in the workplace can be measured or assessed For inhalation, the most appropriate metric for assessment