Potential Health Hazards of Nanomaterials
As stated earlier, nanomaterials have a larger surface area to volume ratio compared to larger materials of the same composition. Nanomaterials, like many other solids, can have biological impacts based on their structure. Below is a summary of known and suspected health hazards from nanomaterials, based on recent research in animal models and in vitro assays.
A. Respirable Exposures
Inhalation is the most likely exposure route in laboratory settings, and the most extensive health effects studies have involved the inhalation route. From the time when carbon nanotubes were first seen through transmission electron microscopy, investigators noticed a startling physical similarity to asbestos (Figure 18.3). Both exist as fibers; with a length/width aspect ratio of at least 3:1, and both can exist at nanoscale (asbestos fibers as small as 2.5 nm diameter can occur naturally). Several decades of experimental data and retrospective epidemiological evidence have shown that asbestos exposure can lead to pulmonary fibrosis, mesothelioma, and increased risk of lung cancer, which is strongly synergistic when combined with smoking. Can CNTs cause similar health effects?
CNTs can, like asbestos, reach the gas exchange (alveolar) regions of the deep lung, and trigger inflammation and oxidative stress. Studies in mice have shown that single-walled CNTs can produce pulmonary granulomas, whereas equivalent mass doses of ultrafine carbon black did not6,7. This implies that the shape and surface chemistry properties of CNTs impart an increase in pulmonary toxicity.
Respiratory studies for other nanomaterials are also informative. Extensive research on diesel exhaust particulates has led to their characterization by the International Agency for Research on Cancer as a reasonably anticipated human lung carcinogen. For titanium dioxide (a substance used at nanoparticle size in cosmetics, sunscreens, and self-cleaning windows), 25 nm diameter particles produced more potent lung damage than 250 nm diameter particles8. Since both sizes of particles are capable of reaching the deep lung, there must be another factor such as surface area to volume ratio, solubility, or agglomeration creating the toxicity difference. Nanoparticles that agglomerate tend to deposit in the nasopharyngeal region or the upper airways.
Discrete nanoparticles that reach the deep lung might be small enough to penetrate through alveolar epithelial cells, enter the capillaries, and translocate to other organs9. For discrete nanoparticles that remain in the nasopharyngeal region, translocation to the brain via axonal transport through the olfactory nerve has been shown in rats10.
In summary, animal studies indicate the following potential concerns from exposures to nanomaterials through the inhalation route:
- CNTs might possess asbestos-like properties
- For all nanomaterials, equivalent mass doses of the same materials might exhibit higher toxicity at nanoscale size
- Previously unobserved translocation routes (via alveoli to bloodstream, via olfactory nerve to brain) might exist
B. Skin Exposures
Skin penetration might be a viable exposure route for nanomaterials, though it is too soon to know whether it represents an important exposure route. Studies of titanium dioxide nanoparticles (found in some cosmetics and sunscreens) found that these particles did not penetrate beyond the epidermis11. Another study has shown that quantum dot nanomaterials with varying physicochemical properties were able to penetrate the intact skin of pigs12. Localized effects are also possible, as shown in vitrowhen CNTs were absorbed into skin cells leading to cytokine production and oxidative stress13.
C. Ingestion Exposures
Very little is known about potential adverse effects from exposure to nanomaterials by ingestion. Ingestion might be the least likely exposure route in a laboratory or workplace setting. Ingestion could occur directly by mouth, or indirectly through mucociliary clearance of upper airways. It is presumed that nanomaterials could reach just about any organ or tissue after ingestion, if they are capable of penetrating skin cells, alveolar epithelium, and blood vessel walls.
6Shvedova et al. Unusual Inflammatory and Fibrogenic Pulmonary Responses to Single-Walled Carbon Nanotubes in Mice. Am J Physiology – Lung, Cell, & Mol Physiol 289: L698-L708 (2005).
7Lam CW, James JT, McCluskey R, Arepalli S, Hunter RL. Pulmonary Toxicity of Single-Wall Carbon Nanotubes in Mice 7 and 90 Days after Intratrachial Installation. Toxicol Sci 77: 126-134 (2004).
8Oberdörster, G. Phil. Trans. Roy. Soc. London Series A 358(1775):2719-2740 (2000).
9Oberdörster et al. Extrapulmonary translocation of ultrafine carbon particles following whole-body inhalation exposure of rats. J Toxicol Environ Health 65 Part A(20): 1531-1543 (2002).
10Oberdörster et al. Translocation of inhaled ultrafine particles to the brain. Inhal Toxicol 16(6-7): 437-445 (2004).
11The Royal Society, The Royal Academy of Engineering. Nanoscience and Nanotechnologies. London, UK: The Royal Society and the Royal Academy of Engineering: http://www.nanotec.org.uk/finalReport.htm (2004).
12Ryman-Rasmussen JP, Riviere JE, Monteiro-Riviere NA. Penetration of Intact Skin by Quantum Dots with Diverse Physicochemicals Properties. Toxicol Sci 91(1): 159-165 (2006).
13 Monteiro-Riviere et al. Multi-walled carbon nanotube interactions with human epidermal keratinocytes. Toxicol Lett 155(3): 377-384 (2005).