Summary

Research in the nanoparticle (NP) and nanotechnology field is growing at a breathtaking pace. The reason is simple: the unique properties of NP will allow the development of products with unprecedented characteristics and opportunities in every field of human activity, and with tremendous economic impacts. It is currently anticipated that the number of exposed Quebec workers, not only in manufacturing these products but also in using and processing them, will increase over the next few years. Several products are already available commercially and some Quebec companies now have large-scale NP production capacity.

While technological research is already well established, with many transfers to industrial production, research on occupational health and safety (OHS) risk assessment has lagged behind significantly. Fortunately, the latter has shown strong growth in the scientific community over the last ten years. An initial evaluation of existing knowledge concerning nanoparticle health risks had been published by our team in early 2006 and covered the literature up to 2004. This report is the second edition and incorporates scientific knowledge up to mid-2007.

Insoluble or low-solubility nanoparticles in biological fluid are the greatest cause for concern. Because of their tiny size, several studies have shown behaviour unique to NP. Some of them can pass through our various defence mechanisms and be transported through the body in insoluble form. Thus, some NP can end up in the bloodstream after passing through all the respiratory or gastrointestinal membranes. They are then distributed to various organs and accumulate at specific sites. Others travel along the olfactory nerves and penetrate directly into the brain, while still others pass through cell barriers and reach the nucleus of the cell. These properties, extensively studied in pharmacology, could allow NP to be used as vectors to carry drugs to targeted body sites, including the brain. The corollary is that undesirable NP could be distributed through the bodies of exposed workers and has deleterious effects.

In toxicology the effects are normally correlated to the quantity of product to which individual animals or humans are exposed. The greater the mass absorbed, the greater the effect. In the case of NP, it has been clearly shown that the measured effects are not linked to the mass of the product, which challenges our entire approach to the classical interpretation of toxicity measurement. It is clearly shown that at equal mass, NP are more toxic than products of the same chemical composition but of greater size.

Although several studies find a good correlation between the specific surface and the toxic effects, a consensus seems to be emerging in the scientific community that several factors can contribute to the toxicity of these products and that it is currently impossible, with our limited knowledge, to weight the significance of each of these factors or predict the precise toxicity of a new nanoparticle. The published studies link the observed effects to different parameters: specific surface, number of particles, size and granulometric distribution, concentration, surface dose, surface coverage, degree of agglomeration of the particles and pulmonary deposition site, the “age” of the particles, surface charge, shape, porosity, crystalline structure, electrostatic attraction potential, particle synthesis method, hydrophilic/hydrophobic character and post-synthesis modifications (grafting of organic radicals or surface coverage to prevent aggregation). The presence of certain contaminants, such as metals, can also favour free radical formation and inflammation, while the chemical composition and delivery of surface components, NP colloidal and surface properties, compartmentation in the lung passages and biopersistence are other factors adding a dimension of complexity to the understanding of their toxicity. The slow dissolution of certain NP or NP components in the body can become a major factor in their toxicity. These various factors will influence the functional, toxicological and environmental impact of NP.

Several effects have already been shown in animals. Among these, toxic effects have been identified in several organs (heart, lungs, kidneys, reproductive system…), as well as genotoxicity and cytotoxicity. For example, some particles cause granulomas, fibrosis and tumoural reactions in the lungs. Thus, titanium dioxide, a substance recognized as having low toxicity, shows high pulmonary toxicity on the nano-scale in some studies and no or almost no effects in other studies. In general, the toxicological data specific to nanoparticles remains limited, often rendering quantitative risk assessment difficult due to the small number of studies for most substances, the short exposure period, the different composition of the nanoparticles tested (diameter, length and agglomeration), or the often-unusual exposure route in the work environment. Additional studies (absorption, biopersistence, carcinogenicity, translocation to other tissues or organs, etc.) are necessary for quantitative assessment of the risk associated with inhalation exposure and percutaneous exposure of workers.

Although major trends may emerge and show numerous toxic effects related to certain NP, it can be seen that each product, and even each synthesized NP batch, can have its own toxicity. Any process or surface modification can have an impact on the toxicity of the resulting product.

Given this context, the authors of this report consider that the IRSST should favour the introduction of strict prevention procedures, which remain the only way to prevent the development of occupational diseases. Thus, the authors strongly recommend that the IRSST concentrate its future research efforts on developing exposure assessment strategies and tools, and on the development and measurement of the effectiveness of control methods for occupational NP exposure.