Chapter 10: Nanomaterials
Revised January 2022
Nanomaterials are materials with one, two, or three external dimensions in the size range of 1 – 100 nm. Subcategories of nanomaterials include: 1) nanoplates, which have one external dimension at the nanoscale, 2) nanofibers, which have two external dimensions at the nanoscale, with a nanotube defined as a hollow nanofiber, and 3) nanoparticles, which have all three external dimensions at the nanoscale.
The term “nanomaterials” and the subcategory terms listed above are generally used to describe engineered nanoscale materials, while the term “ultrafine particle” is used for airborne particles smaller than 100 nm in diameter that are incidental products of combustion and vaporization. For the purposes of this chapter we are concerned with engineered materials and the “nano” terms will be used.
In addition to the health risks associated with the chemical composition of a particular nanomaterial, the small size of the material poses additional risks. Currently there are gaps in knowledge with regard to routes of exposure, translocation of materials within the body, and interaction of materials with biological systems and cellular components.
It is clear that the very small size of nanoparticles confers unique characteristics relative to larger particles which influence their migration and deposition in the body, and therefore, their toxicity. For example, nanoparticles can cross cell membranes and gain access to organelles such as mitochondria, where they have been shown to cause oxidative damage and impair function of cells in culture. Nanoparticles can cross the blood-brain barrier to gain access to the brain and studies involving mice and rats exposed to metal nanoparticles have shown adverse effects on the brain.
Toxicity information for larger particles provides baseline knowledge about nanoparticles of similar chemical composition. Due to nanoparticles having a greater surface area than an equivalent mass of larger particles, the toxicity of nanoparticles is greater than that of larger particles of similar chemical composition. In addition to surface area, the toxicity of nanoparticles is dependent on its surface chemistry. For example, particle surface reactivity can greatly influence toxicity and particles with greater reactive surface oxidant generation produce more reactive oxygen species and greater pulmonary inflammation. Because of these factors, predicting the toxicity of a nanoparticle based only on its chemical composition may result in underestimation and lead to an inadequate level of protection for exposed personnel.
Primary Health Effects
Like other xenobiotics, the potential health risk associated with exposure to nanoparticles is dependent on the magnitude, duration and frequency of exposure; persistence in the body; ability to be translocated in the body; particle toxicity; and the susceptibility and health status of the exposed individual. The biological persistence and toxicity of particles are in turn dependent on specific particle characteristics, to include surface chemistry, physical structure, and particle size and tendency of particles to agglomerate. Potential health effects are therefore variable and dependent on the specifics of the nanoparticles.
Animal studies indicate that health effects associated with inhalation of nanoparticles include pulmonary inflammation, lung fibrosis, and lung tumors. Mice exposed to single-walled carbon nanotubes (SWCNTs) via instillation in the lungs developed interstitial inflammation and epitheloid granulomas in a dose-dependent (0.1 or 0.5 mg per mouse) manner, with mortality observed in the high dose group when exposed to SWCNTs that contained nickel. Exposure of mice to SWCNTs via pharyngeal aspiration (10 – 40 µg per mouse) produced transient pulmonary inflammation, oxidative stress, decrease in pulmonary function, decrease in bacterial clearance, and early onset of interstitial fibrosis. Studies involving exposure of mice to multi-walled carbon nanotubes (MWCNT) showed that mice exposed to both a cancer initiator chemical and MWCNT (by inhalation) were significantly more likely to have tumors than mice exposed only to the initiator chemical. This study did not indicate that MWCNT can cause cancer alone but that they increased the risk of cancer in mice also exposed to the initiator chemical.
Studies of workers exposed to ultrafine particles have reported adverse lung effects to include decreased lung function, obstructive lung disease, and fibrotic lung disease. Some studies have also shown elevated lung cancer and neurological effects among exposed workers. The specific relevance of these findings to occupational exposure to nanoparticles is not known with certainty but it is currently thought that nanoparticles produce health effects similar to those produced by ultrafine particles.
Routes of Exposure
Inhalation is the most common route of exposure for particles and due to their very small size nanoparticles are deposited in the lungs to a greater extent than are larger respirable particles. Nanoparticles deposited in the lungs can enter the bloodstream and be translocated to other organs. Animal studies have shown that nanoparticles deposited in the nasal region can be translocated to the brain via the olfactory nerve, which does not occur with larger particles.
Studies with human skin samples and dermal exposure of animals have shown that nanoparticles can penetrate skin by passive diffusion through the stratum corneum, analogous to lipophilic liquid chemicals. Although it is not known how these findings relate to occupational skin exposure, it should be assumed that nanoparticles have the ability to pass through intact skin.
Ingestion of nanomaterials can occur from hand-to-mouth transfer or may accompany inhalation of nanomaterials since inhaled particles that are cleared from the respiratory tract via the mucociliary escalator may be swallowed. There is currently not much known about potential health effects from ingestion of nanomaterials.
Potential Exposures to Nanomaterials
The potential for exposure to nanomaterials is analogous to that of other particles and is dependent on the form of the nanomaterial, processes involved in manipulation of the nanomaterial, and physiochemical properties of the nanomaterial (e.g., particle size and tendency to agglomerate). Nanomaterials that are in a powder form easily become airborne and present a higher exposure risk than do nanomaterials that are in liquid media as a slurry or suspension. Components or devices made up of nanomaterials present minimal risk of exposure unless disturbed in a manner that can release nanoparticles (e.g., cutting or grinding). Some situations that increase the potential for exposure to nanomaterials include the following:
- Working with nanomaterials (powders or in liquid media) without adequate skin protection
- Pouring or mixing liquid suspensions or performing other manipulations involving vigorous agitation
- Generating nanomaterials in the gas phase without adequate containment
- Handling nanomaterials powder without adequate containment
- Cleaning up spills of nanomaterials
- Mechanical disruption of nanomaterials
Each use of nanomaterials requires an evaluation of the exposure potential that includes assessment of the material being used, the manipulations to be performed, and exposure control measures to be used. Contact the Chemical Hygiene Officer for assistance with evaluation of nanomaterial exposures and safe work practices.
Exposure Limits for Nanomaterials
Currently there are no specific regulatory occupational exposure limits established for nanomaterials. The National Institute of Occupational Safety and Health (NIOSH) has established a Recommended Exposure Limit (REL) for the following:
- Carbon nanotubes and nanofibers: 1 µg/m3 respirable elemental carbon as an 8-hour time-weighted average.
- Titanium Dioxide: 0.3 mg/m3 for ultrafine (including engineered nanoscale) titanium dioxide.
- Silver: 0.9 µg/m3 (Draft) respirable particles as an 8-hour time-weighted average.
Although exposure limits for larger particles of similar chemical composition may not provide sufficient health protection, they may provide a starting point for additional exposure risk assessment. For example, the REL of 1 µg/m3 for carbon nanotubes corresponds to the lowest airborne carbon nanotube concentration that can be accurately measured by established air sampling methods rather than a protective level based on toxicity. It is recommended that exposures be kept as low as possible below the REL. Limits for exposure to nanomaterials will need to be evaluated based on an assessment of the specific nanomaterial in consultation with the Chemical Hygiene Officer.
Minimizing Exposures to Nanomaterials
Exposure to nanomaterials can be controlled using local exhaust ventilation devices and dispersible nanomaterials must always be handled in a ventilated containment device. The effectiveness of a local exhaust ventilation device is dependent on the design of the device, the ventilation performance of the device, the physical form of the nanomaterial, and the manipulations being performed.
Glove Boxes and Powder Handling Enclosures
A glove box or other ventilated full containment device provides the best protection when handling powders. Powder handling enclosures also provide good containment for handling nanomaterial powders. These devices operate at lower air flow rates and velocities than do traditional chemical fume hoods, reducing the potential for loss or ejection of nanomaterials. Flow Sciences is one manufacturer of powder handling enclosures for nanotechnology applications.
Biological Safety Cabinets
Although Class II biological safety cabinets (BSCs) are designed to contain infectious aerosols that are produced when handling pathogenic microorganisms, they also provide protection when handling nanomaterials. BSCs can be used when handling powders, although they do not provide as effective containment as do glove boxes or powder handling enclosures. BSCs used for handling nanomaterials should have their exhaust ducted to the outside environment via a thimble connection (Class II, type A1 or A1) or via continuous hard ducting (Class II, type B1 or B2).
Chemical Lab Hoods (Fume Hoods)
Traditional chemical lab hoods may not provide adequate containment when handling powders due to higher air flow and turbulence. Lab hoods are generally not appropriate for use with powders but may be adequate for nanomaterials in liquid media or agglomerated form which are not as easily dispersed. It is recommended that the exhaust air from lab hoods that are used for handling nanomaterials pass through a high efficiency particulate air (HEPA) filter prior to release to the environment.
Safe Work Practices
Substitution of nanomaterials is usually not possible for researchers; however, less hazardous options may be available with respect to the form of the nanomaterial used, manipulations performed, and associated chemical use. For example, working with nanomaterials suspended in a liquid rather than as a dry powder reduces the potential for airborne release. Gentler manipulations involving less vigorous agitation should be used whenever possible as this reduces the likelihood of aerosolization. Hazardous chemical use is often required in nanomaterial research and substituting less hazardous chemicals for more hazardous chemicals will reduce the overall risk of the process.
In addition to the good laboratory safety practices contained in Chapter 2, the following prudent work practices should be implemented to minimize personnel exposure to nanomaterials.
- Minimize access to nanomaterials those personnel who are specifically trained and authorized.
- When working with nanomaterials, limit the number of personnel in the immediate area to only those who are directly needed to perform the work.
- Work in ventilated containment whenever possible.
- Keep containers of nanomaterials closed except when removing or adding material.
- Maintain good housekeeping of nanomaterial work areas.
- Work on disposable protective covering material (“lab diapers”) to reduce contamination of surfaces and to facilitate clean up.
- Clean all surfaces potentially contaminated with nanomaterials when work is completed or the end of each day using wet wiping or a HEPA-filtered vacuum that is leak tested annually; never dry sweep.
- Clean up spills as soon as possible using wet wiping and/or a HEPA-filtered vacuum that is leak tested annually.
- Collect and handle nanomaterial-containing waste in sealed, labeled containers in a manner that minimizes potential exposure during handling and disposal.
- For work involving handling of large quantities of dry powders, and other work with higher risk of contamination, consider use of disposable coveralls, use of dedicated work clothing and showering when work is completed, and other procedures to reduce the likelihood of contaminating other areas (including take-home contamination). Consideration of these special procedures should be justified by risk assessment.
Personal Protective Equipment
Generally, personal clothing and protective equipment that is appropriate for wet-chemistry work (see Chapter 13) is required for work with nanomaterials. This includes clothing that covers legs and closed toes shoes that cover the foot, with a lab coat, appropriate chemical resistant gloves, and eye protection (with face protection as needed). Additional personal protective equipment considerations and requirements are provided below.
Respirators should be worn when there is potential for exposure to airborne nanomaterials. HEPA-filtered respirators (those with N100, P100, or R100 particulate cartridges) provide the highest level of protection against nanoparticles (other than supplied air respirators) and should generally be worn. N95 respirators may be adequate in cases where only low level exposure may be possible or as a supplement where airborne exposures are not expected. The selection of respiratory protection must be based on an assessment of risk. Contact the Chemical Hygiene Officer for assistance.
Chemically impervious gloves that are appropriate for the nanomaterials and chemicals being used are required. Selection of gloves must take into account the nanomaterial and liquid that the nanomaterial is suspended in (see Chapter 13). Nanoparticles may be translocated through microscopic breaches in glove material so gloves should be replaced often and immediately upon visible signs of cracks or other visible wear. Gloves should overlap lab coat sleeves to prevent exposure of lower forearms. Gloves must be removed carefully and using good technique to avoid spreading contamination and aerosolizing nanomaterials.
At a minimum, a full laboratory coat must be worn when handling nanomaterials. Procedures involving higher risk of exposure may require use of disposable coveralls or other protective clothing. Used lab coats and other body protective clothing must remain in nanomaterial work areas unless contained in sealed plastic bags. Disposable lab coats and coveralls must be disposed of in sealed plastic bags as advised by EH&S. Non-disposable lab coats must be laundered on a regular basis, with transport in sealed plastic bags.
Fire and Explosion Control
Carbon-containing dusts and metal dusts can explode if sufficient airborne concentration is achieved in the presence of adequate oxygen and an ignition source. Because of their greater surface-to-volume ratio nanoparticles represent a greater risk of explosion than an equivalent concentration of larger particles. Laboratory scale work poses a lower risk of explosion than does larger scale work in pilot plants or manufacturing facilities; however, generation of high airborne concentrations of nanoparticles are to be avoided. Use of ventilated containment, in concert with good housekeeping to prevent accumulation on surfaces, should prevent this possibility.
Additional Information on Nanomaterials Safety
National Institute for Occupational Safety and Health (NIOSH), Nanotechnology, Guidance and Publications:
- Approaches to Safe Nanotechnology: Managing the Health and Safety Concerns Associated with Engineered Nanomaterials
- General Safe Practices for Working with Engineered Nanomaterials in Research Laboratories
- Sharma, HS and Sharma A, Neurotoxicity of Engineered Nanoparticles From Metals, CNS Neurol Disord – Drug Targets, 2012, 11(1): 65-80.
- Occupational Exposure to Titanium Dioxide, NIOSH Current Intelligence Bulletin 63.
- Occupational Exposure to Carbon Nanotubes and Nanofibers, NIOSH Current Intelligence Bulletin 65.