Stanford University

Nanomaterials

This section provides environmental, health and safety guidance to researchers working with engineered nanomaterials in Stanford University laboratories. It is intended to supplement the requirements of Stanford University’s Chemical Hygiene Plan and its companion Laboratory Safety Toolkit.

As the scientific community continues to gather data to assess the potential health and safety risks associated with engineered nanomaterials and more information becomes available, these guidelines may be updated. Until more is known about the possible risks of nanomaterials, it is prudent and appropriate to take a precautionary approach and to utilize good laboratory safety practices when working with these materials.

Action items for faculty working with or creating engineered nanomaterials

  • Review the General Principles and Practices for Working Safely with Engineered Nanomaterials document.
  • Instruct all research personnel in your lab to follow the work practices described in the document.
  • Create standard operating procedures (SOPs) for processes and experiments involving nanomaterials using the guidance in the SOP section. Priority for SOP development should be given to those operations where there is higher risk of exposure (e.g. manipulation of nanoparticles in a gas stream or work with dry dispersible nanoparticles).

What are nanomaterials?

Nanomaterials are defined as materials with at least one external dimension in the size range from approximately one to 100 nanometers. Nanoparticles are objects with all three external dimensions at the nanoscale.1 Nanoparticles that are naturally occurring (e.g. volcanic ash or soot from forest fires) or are the incidental byproducts of combustion processes (e.g. welding, diesel engines) are usually physically and chemically heterogeneous, and are often termed ultrafine particles.

Engineered nanoparticles are intentionally produced and designed with very specific properties related to shape, size, surface properties, and chemistry. These properties are reflected in aerosols, colloids, or powders. Often, the behavior of nanomaterials may depend more on surface area than particle composition itself. Relative surface area is one of the principal factors that enhance reactivity, strength, and electrical properties.

Engineered nanoparticles may be bought from commercial vendors or generated via experimental procedures by lab researchers. Examples of engineered nanomaterials include carbon buckeyballs or fullerenes, carbon nanotubes, metal or metal oxide nanoparticles (e.g. gold or titanium dioxide), and quantum dots, among many others.

Occupational Health & Safety Concerns
  1. Exposure to nanomaterials may occur through inhalation, dermal contact, or ingestion, depending on how personnel use them. The full health effects of exposures to nanomaterials are not fully understood. For example, a peer-reviewed toxicity study on carbon nanotubes (CNTs) indicated that the toxicity of nanoparticles depends on specific physiochemical and environmental factors, and thus the toxic potential of each nanoparticle needs to be evaluated separately.Results of existing studies on animals or humans provide some basis for preliminary estimates of areas of concern.

    According to the National Institute for Occupational Safety and Health (NIOSH)2, studies to date have indicated:

    • Increased toxicity of ultrafine particles or nanoparticles as compared to larger particles of similar composition. Chemical composition and other particle properties can also influence toxicity.19, 20, 21, 24, 15, 29, 4, 7, 3, 16, 6
    • A greater proportion of inhaled nanoparticles will deposit in the respiratory tract, as compared to larger particles.11, 12, 5, 13
    • Nanoparticles can cross cell membranes and interact with subcellular structures, where they have been shown to cause oxidative damage and impair function of cells in culture.17, 18, 10
    • Nanoparticles may be capable of penetrating healthy intact skin and translocating to other organ systems following penetration.28, 14, 22, 23, 27, 10
    • Catalytic effects and fire or explosion may present hazards.25

Preparation
  1. Training

    • Ensure that researchers have both general safety training and lab-specific training relevant to the nanomaterials and associated hazardous chemicals used in the process or experiment. See the safety training section for guidance on training.
    • Lab-specific training can include a review of this safety fact sheet, the relevant safety data sheets (if available), and the lab’s standard operating procedure for the experiment.

    Standard operating procedures

    • Prepare a standard operating procedure (SOP) for operations involving nanomaterials. For guidance on creating SOPs, see the SOP section. The SOP should be specific to the proposed procedure.
    • Consider the hazards of the precursor materials in evaluating the process.
    • Special consideration should be given to the high reactivity of some nanopowders with regard to potential fire and explosion.

    Consultation

    • Consult with the PI prior to procuring or working with nanomaterials.
    • Review the Chemical Safety section on consultation and prior approvals.
    • For additional assistance, contact EH&S’s Occupational Health & Safety Program at (650) 723-0448.

Safe Handling Procedures
  1. Exposure standards have not been established for engineered nanoparticles in the United States or internationally.26 Until more definitive findings are made regarding the potential health risks of handling nanomaterials, researchers planning to work with nanomaterials must implement a combination of engineering controls, work practices, and personal protective equipment to minimize potential exposures to themselves and others.

    For a quick guide to the exposure risks and prudent control measures to be used for common laboratory operations involving nanomaterials, refer to the table in the Exposure Risks and Control Measures for Common Laboratory Operations tab. It’s important to consider if the nanoparticles are in an agglomerated or aggregated form, functionalized, suspended in liquid, or bound, as these conditions may affect the exposure potential.

    Engineering controls

    • Use glove bags, glove boxes, fume hoods, or other containment or exhausted enclosures when there is a potential for aerosolization, such as:
      • Handling powders
      • Creating nanoparticles in gas phase
      • Pouring or mixing liquid media which involves a high degree of agitation. (Do not use horizontal laminar flow hoods (clean benches), as these devices direct the air flow towards the worker.) Consult with EH&S if engineering controls are not feasible.
    • Use fume hoods or other local exhaust devices to exhaust tube furnaces and/or chemical reaction vessels.
    • Perform any maintenance activities, such as repair to equipment used to create nanomaterials or cleaning/replacement of dust collection systems, in fume hoods or under appropriate local exhaust.

    Work practices

    Selection of nanomaterials

    • Whenever possible, handle nanomaterials in solutions, or attached to substrates, to minimize airborne release.
    • Consult the safety data sheet (SDS), if available, or other appropriate references prior to using a chemical or nanomaterial with which you are unfamiliar. Note that information contained in some MSDSs may not be fully accurate and/or may be more relevant to the properties of the bulk material, rather than the nano-size particles.

    Safety equipment

    Know the location and proper use of emergency equipment, such as safety showers, fire extinguishers, and fire alarms.

    Hygiene

    • Do not consume or store food and beverages or apply cosmetics where chemicals or nanomaterials are used or stored, since this practice increases the likelihood of exposure by ingestion.
    • Do not use mouth suction for pipetting or siphoning.
    • Wash hands frequently to minimize potential chemical or nanoparticle exposure through ingestion and dermal contact.
    • Remove gloves when leaving the laboratory so as not to contaminate doorknobs, or when handling common use objects such as phones, multiuser computers, etc.

    Labeling and signage

    • Store in a well-sealed container that can be opened with minimal agitation of the contents.
    • Label all chemical containers with the identity of the contents. Avoid abbreviations or acronyms. Include “nano” in the descriptor (i.e. label as “nano-zinc oxide particles” rather than “zinc oxide”). Include hazard warning and chemical concentration information, if known.
    • Use cautious judgment when leaving operations unattended:
      • Post signs to communicate appropriate warnings and precautions.
      • Anticipate potential equipment and facility failures.
      • Provide appropriate containment for accidental release of hazardous chemicals.

    Cleaning

    Wet wipe and/or HEPA-vacuum work surfaces regularly.

    Transporting

    Use a sealed, double-contained container when transporting nanomaterials inside or outside of the building.

    Buddy system

    Communicate with others in the building when working alone in the laboratory. Let them know when you arrive and leave. Avoid working alone in the laboratory when performing high-risk operations.

    Spill response

    In addition to following EH&S general spill response directions, integrate these additional measures for spills involving nanomaterials:

    • Use wet cleanup methods or vacuum cleaners equipped with HEPA-filters.
    • Do not dry sweep or use conventional vacuum cleaners.
    • Collect spill cleanup materials in a tightly closed container.
    • Manage spill cleanup debris as hazardous waste.

    Disposal

    As a prudent measure, manage nanoparticle wastes, including contaminated lab debris, as a part of your normal laboratory hazardous waste stream.

    Collect and store waste materials in a tightly closed container. Include information describing the nanoparticulate nature of the materials on the waste tag (e.g. “contains nanosilver material”).

    Personal protective equipment

    • Wear gloves, lab coats, safety goggles, long pants, closed-toe shoes, and face shields, as appropriate, based on the nature of the materials and procedure.
    • If work cannot be conducted inside a fume hood or other ventilated enclosure, consult with EH&S’s Occupational Health and Safety Program regarding the need for respiratory protection or other alternative controls.

Exposure Risks & Control Measures for Common Lab Operations
  1. Use this table to assess exposure risks and to implement control measures for common lab operations involving nanomaterials.

    Activity types, by risk of exposure Primary control measures
    Low probability:

    • Non-destructive handling of solid nanoparticle composites or nanoparticles permanently bonded to a substrate
    • Dispose nitrile or PVC gloves. Do not reuse gloves
    • Wet cleaning procedures and/or HEPA vacuum for surfaces and equipment
    Medium or high probability:

    • Working with nanomaterials in liquid media during pouring or mixing, or where a high degree of agitation is involved (e.g. sonication)
    • Handling nanostructured powders*
    • High speed abrading/grinding nano-composite materials
    • Maintenance on equipment used to produce nanomaterials
    • Cleaning of dust collection systems used to capture nanoparticles
    • Conduct task within a fully enclosed system (e.g. glovebox) or fume hood
    • Disposable gloves are appropriate for the solvent in which the particles are suspended. Do not reuse gloves
    • Use safety eyewear (and a face shield if splash potential exists).
    • Wet cleaning procedures for surfaces and equipment
    High probability:

    • Generating nanoparticles in the gas phase or in aerosol (spill or liquid)
    • Manipulation of nanoparticles in gas stream
    • Work in enclosed systems only (e.g. glovebox, glovebag, or sealed chamber)

    * EH&S recognizes that low-density nanomaterials (e.g. carbon-based) become aerosolized by even the slightest air movement and may not be practical when weighed or handled in laboratory fume hoods. Consult with EH&S on alternative sets of controls.


Citations
  1. [1] National Institute for Occupational Safety and Health (NIOSH) Approaches to Safe Nanotechnology: Managing the Health and Safety Concerns Associated with Engineered Nanomaterials (March 2009).  https://www.cdc.gov/niosh/docs/2009-125/

    [2] National Institute for Occupational Safety and Health (NIOSH) Approaches to Safe Nanotechnology: Managing the Health and Safety Concerns Associated with Engineered Nanomaterials (March 2009).  https://www.cdc.gov/niosh/docs/2009-125/

    [3] Barlow PG, Clouter-Baker AC, Donaldson K, MacCallum J, Stone V [2005].  Carbon black nanoparticles induce type II epithelial cells to release chemotaxins for alveolar macrophages.  Particle and Fiber Toxicol 2, 14 pp [open access].

    [4] Brown DM, Wilson MR, MacNee W, Stone V, Donaldson K [2001]. Size-dependent proinflammatory effects of ultrafine polystyrene particles: A role for surface area and oxidative stress in the enhanced activity of ultrafines. Toxicology and Applied Pharmacology 175(3): 191-199.

    [5] Daigle CC, Chalupa DC, Gibb FRMorrow PE, Oberdorster G, Utell MJ, Frampton MW [2003]. Ultrafine particle deposition in humans during rest and exercise. Inhalation Toxicol 15(6):539–552.

    [6] Donaldson K, Aitken R, Tran L, Stone V, Duffin R, Forrest G, Alexander A. [2006] Carbon Nanotubes: a Review of Their Properties in Relation to Pulmonary Toxicology and Workplace Safety. Toxicol Sci. 92(1): 5-22.

    [7] Duffin R, Tran CL, Clouter A, Brown DM, MacNee W, Stone V, Donaldson K [2002]. The importance of surface area and specific reactivity in the acute pulmonary inflammatory response to particles. Ann Occup Hyg 46:242–245.

    [8] Duffin R, Tran L, Brown D, Stone V, Donaldson K [2007]. Proinflammogenic effects of low-toxicity and metal nanoparticles in vivo and in vitro: highlighting the role of particle surface area and surface reactivity. Inhal Toxicol 19(10):849–856.

    [9] Helland A, Wick P, Koehler A, Schmid K, Som C [2007]. Reviewing the Environmental and Human Health Knowledge Base of Carbon Nanotubes. Environ Health Perspectives 115(8):1125-1131.

    [10] Geiser M, Rothen-Rutishauser B, Kapp N, Schurch S, Kreyling W, Schulz H, Semmler M, Im Hof V, Heyder J, Gehr P [2005].  Ultrafine particles cross cellular membranes by nonphagocytic mechanisms in lungs and in cultured cells.  Environ Health Perspectives 113(11):1555-1560.

    [11] ICRP [1994]. Human respiratory tract model for radiological protection. Oxford, England: Pergamon, Elsevier Science Ltd., International Commission on Radiological Protection Publication No. 66.

    [12] Jaques PA, Kim CS [2000]. Measurement of total lung deposition of inhaled ultrafine particles in healthy men and women. Inhal Toxicol 12(8):715–731.

    [13] Kim CS, Jaques PA [2004].  Analysis of total respiratory deposition of inhaled ultrafine particles in adult subjects at various breathing patterns.  Aerosol Sci Technol 38:525-540.

    [14] Kreyling WG, Semmler M, Erbe F, Mayer P, Takenaka S, Schulz H, Oberdorster G,  Ziesenis A [2002]. Translocation of ultrafine insoluble iridium particles from lung epithelium to extrapulmonary organs is size dependent but very low. J Toxicol Environ Health 65(20):1513–1530.

    [15] Lison, D., C. Lardot, F. Huaux, G. Zanetti,  Fubini B [1997]. Influence of particle surface area on the toxicity of insoluble manganese dioxide dusts. Arch. Toxicol. 71(12): 725-729.

    [16] Maynard AM, Kuempel ED [2005]. Airborne nanostructured particles and occupational health.  J Nanoparticle Research 7(6):587-614.

    [17] Moller W, Hofer T, Ziesenis A, Karg E, Heyder J [2002]. Ultrafine particles cause cytoskeletal dysfunctions in macrophages. Toxicol Appl Pharmacol 182(3): 197-207.

    [18] Moller W, Brown DM, Kreyling WG, Stone V [2005]. Ultrafine particles cause cytoskeletal dysfunctions in macrophages: role of intracellular calcium. Part Fibre Toxicol. 2:7, 12pp.

    [19] Oberdörster G, Ferin J, Gelein R, Soderholm SC, Finkelstein J [1992]. Role of the alveolar macrophage in lung injury—studies with ultrafine particles. Environ Health Perspect 97:193–199.

    [20] Oberdörster G, Ferin J, Lehnert BE [1994a]. Correlation between particle-size, in-vivo particle persistence, and lung injury. Environ Health Perspect 102(S5):173–179.

    [21] Oberdörster G, Ferin J, Soderholm S Gelein R, Cox C, Baggs R,  Morrow PE [1994b]. Increased pulmonary toxicity of inhaled ultrafine particles: due to lung overload alone? Ann. Occup. Hyg. 38(Suppl. 1): 295-302.

    [22] Oberdörster G, Sharp Z, Atudorei V, Elder A, Gelein R, Lunts A, Kreyling W, Cox C [2002]. Extrapulmonary translocation of ultrafine carbon particles following whole-body inhalation exposure of rats. J Toxicol Environ Health 65 Part A(20):1531–1543.

    [23] Oberdörster G, Sharp Z, Atudorei V, Elder A, Gelein R, Kreyling W, Cox C [2004]. Translocation of inhaled ultrafine particles to the brain. Inhal Toxicol 16(6–7):437–445.

    [24] Oberdörster G, Oberdörster E, Oberdörster J [2005a]. Nanotoxicology: an emerging discipline evolving from studies of ultrafine particles. Environ Health Perspect. 113(7):823–839.

    [25] Pritchard DK [2004]. Literature review—explosion hazards associated with nanopowders. United Kingdom: Health and Safety Laboratory, HSL/2004/12.

    [26] “Safe Nanotechnology in the Workplace – An Introduction for Employers, Managers, and Safety and Health Professionals”  [Feb. 2008]. National Institutes of Health.  DHHS (NIOSH) Publication No. 2008-112.

    [27] Semmier M, Seitz J, Erbe F, Mayer P, Heyder J, Oberdorster G, Kreyling WG [2004]. Long-term clearance kinetics of inhaled ultrafine insoluble iridium particles from the rat lung, including transient translocation into secondary organs. Inhal Toxicol 16(6-7): 453-459.

    [28] Takenaka S, Karg D, Roth C, Schulz H, Ziesenis A, Heinzmann U, Chramel P, Heyder J [2001].  Pulmonary and systemic distribution of inhaled ultrafine silver particles in rats.  Environ Health Perspect 109(suppl. 4):547-551.

    [29] Tran CL, Cullen RT, Buchanan D, Jones AD, Miller BG, Searl A, Davis JMG, Donaldson K [1999]. Investigation and prediction of pulmonary responses to dust. Part II. In: Investigations into the pulmonary effects of low toxicity dusts. Contract Research Report 216/1999 Suffolk, UK: Health and Safety Executive.



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