Risk Assessment


EMERGNANO: A review of completed and near completed environment, health and safety research on nanomaterials and nanotechnology, March 2009.


7.4 CONSIDERATION OF THE APPLICATION OF THE PRECAUTIONARY PRINCIPLE

Titanium Dioxide | Iron Oxide | Quantum Dots | Cerium Oxide | Zinc Oxide | Carbon Black |
Nickel | Silicon Oxide | Aluminum Oxide | Carbon Nanotubes | Nanoclays | Silver | Gold | Summary

Titanium dioxide (TiO2) particles
Titanium dioxide nanoparticles are used in significant amounts (greater than 1000 kg/company/year). They are potentially inflammatory, and have been shown to induce oxidative stress in cell culture which is mediated by the generation of free radicals. They have the potential to be environmentally detrimental as their estimated environmental concentration has been calculated to be greater than their no effect concentration, however the nanoparticle size and type was not further defined, the toxic effect not stated, and the data were based on a modelling study. This must be further investigated and steps taken to ensure the environmental safety of titanium dioxide nanoparticles. The Research Objectives have not identified a sufficient body of evidence to make a risk assessment feasible for this nanomaterial, however there is some evidence to suggest that titanium dioxide nanoparticles may be present in the environment at concentrations greater than the predicted no effect concentration.

Iron oxide (FexOx)
Whilst produced in significant amounts, there was no evidence presented in the Research Objectives to suggest that iron oxide nanoparticles are detrimental or beneficial to human health or the environment, therefore a risk assessment was not possible.

Quantum dots
Quantum dots have been shown to cause platelet aggregation, however there is no information on other toxicological properties. Quantum dots do not readily aggregate in drinking water. Limited exposure as experimental use and normally held in solution or a solid matrix. Quantum dots are a general name given to a range of compounds (including cadmium telluride and cadmium selenide) therefore it will be necessary to consider each chemical compound separately. The Research Objectives have not identified a sufficient body of evidence to make a risk assessment feasible for this group of nanomaterials.

Cerium oxide (CeO2)
Although suggested to have relatively low aquatic invertebrate toxicity, the ecotoxicological properties of cerium oxide nanoparticles is currently under investigation. Data suggests that CeO2 nanoparticles are not cytotoxic in vitro (human hepatic cell line), however this may be cell specific and will require further investigation. However, the Research Objectives have not identified a sufficient body of evidence to make a risk assessment feasible for this nanomaterial.

Zinc oxide (ZnO)
Whilst produced in significant amounts, there is no evidence to suggest that zinc oxide nanoparticles are detrimental or beneficial to human health; or the environment. However, the toxicological effects and ecotoxicological effects of zinc oxide nanoparticles are currently being investigated and the Research Objectives have not identified a sufficient body of evidence to make a risk assessment feasible for this nanomaterial.

Carbon black
Carbon black particles are flammable and have been shown to produce oxidative stress mediated inflammatory responses in cell culture. The Research Objectives have not identified a sufficient body of evidence to make a risk assessment feasible for this nanomaterial. Carbon black consists of near-spherical colloidal primary particles which exist outside the production chamber as aggregates consisting of a number of fused primary particles. These aggregates may consist of a few or hundreds of particles, or the particles can be bound together by van der Waals forces in more loosely associated agglomerates (IARC; 1996). The average primary particle diameters in several commercially produced carbon blacks range from 10 to 500 nm, while the average aggregate diameters range from 80 to 810 nm (DFG, 1999, IARC, 1996). The particles are likely to be contaminated by chemicals including polycyclic aromatic hydrocarbons (PAHs), elemental sulphur (DFG, 1999; IARC, 1996; McCunney et al., 2001). Industrial exposure to carbon black particles has been shown to vary with occupation. Carbon black has been thoroughly reviewed by the International Agency for Research on Cancer (IARC, 1996) who concluded that there was “inadequate evidence in humans for the carcinogenicity of carbon black…sufficient evidence in experimental animals for the carcinogenicity of carbon black [and its extracts]”. It has been classified as “possibility carcinogenic to humans (Group 2B)”. The risk associated with carbon black particles has previously been characterised.

Nickel (Ni)
Inhaled nickel nanoparticles have been shown to cause pulmonary inflammation (acute exposure) and systemic inflammation (chronic exposure) which resulted in atherosclerosis in mice models. However, the Research Objectives have not identified a sufficient body of evidence to make a risk assessment feasible for this nanomaterial.

Silicon oxide (SiO2)
Whilst produced in significant quantities, there is no evidence to suggest that amorphous silica nanoparticles are detrimental or beneficial to human health or the environment. Ongoing studies are considering their toxicological behaviour. The Research Objectives have not identified a sufficient body of evidence to make a risk assessment feasible for this nanomaterial. The inhalation of crystalline silica causes irritation and inflammation in the lungs, with chronic exposure causing the condition silicosis, characterised by unique histological nodules and fibrotic scarring of the lung (Green and Vallvathan, 1996). Animal studies have provided lowest observed adverse effect levels (LOAEL) ranging from 1.0 mg/m3 (24 month study) to 2 mg/m3 (6 month study) but it is noted that inhaled silica is much more toxic to humans than rodents (the reported human LOAEL is 0.02 to 0.05 mg/m3) with the main mechanism of damage being cytokine release and apoptosis produced as a result of receptor-mediated signalling (Hamilton et al., 2008). The risk associated with silica particles has previously been characterised.

Aluminium oxide(AlOx)
Whilst produced in significant quantities, there is no evidence to suggest that aluminium oxide nanoparticles are detrimental or beneficial to human health or the environment. However they have been shown to be inflammogenic in cell culture but did not cause oxidative stress. The Research Objectives have not identified a sufficient body of evidence to make a risk assessment feasible for this nanomaterial.

Carbon nanotubes
Carbon nanotubes are increasingly used in industry and research. It has been shown that PPE is effective if used correctly (gloves need to be doubled up). Whilst the cellular toxicity of carbon nanotubes is currently under investigation, they have been shown to cause mitochondrial DNA damage, oxidative stress to the aorta and to be cytotoxic in muscles at high mass concentrations. After installation into the lungs, they have been shown to be pro-fibrotic with some similar effects to asbestos fibres. The inflammatory response has been shown to be via iron-mediated free radical generation. CNT have also been shown to cause oxidative stress in keratinocytes and cultured skin cells. The ecotoxicological effect of CNTs is currently under investigation. The potential of CNTs to cause oxidative stress and cytotoxicity in cell culture, along with the pro-fibrotic response after installation of CNTs into the lungs suggests that caution should be used when handling CNTs. There is currently no indication as to whether CNTs can be released from matrices in products in which they are currently found. Whilst the Research Objectives have not identified a sufficient body of evidence to make a risk assessment feasible for this nanomaterial, there is sufficient evidence to suggest that CNT may be harmful to human health and therefore the use of the precautionary principle should be considered in this case. As noted, we are aware that the UK HSE is in the process of developing specific guidelines for the control of exposure to CNTs.

Nanoclays
Whilst produced and used in food packaging, there is no evidence to suggest that nanoclays are detrimental or beneficial to human health or the environment. The Research Objectives have not identified a sufficient body of evidence to make a risk assessment feasible for this nanomaterial.

Silver (Ag)
The Research Objective reports present indicative evidence of the harm of silver nanoparticles at low concentrations on aquatic invertebrates, which suggest that the environmental release of silver nanoparticles will be detrimental for the environment and that any industry/institute using silver nanoparticles should consider taking the necessary steps to reduce or eliminate the potential exposure of the environment to these nanoparticles. The Research Objectives have not identified a sufficient body of evidence to make a risk assessment feasible for this nanomaterial; however there is sufficient evidence to suggest that silver nanoparticles may be harmful to the environment and therefore the use of the precautionary principle should be considered in this case.

Gold (Au)
Gold nanoparticles will translocate into the brain after installation in the nose, but this does not occur if the particles are installed into the lungs. As small particles are more likely to travel further into the respiratory system before being removed, it is likely that the exposure to humans will be through the lungs. After injection, coated gold nanoparticles were found in the liver, spleen and bone marrow of rats, although a different coating enhanced the retention of the nanoparticles in the blood compartment. Whilst this suggests that gold nanoparticles translocate within the body, there is no suggestion of toxicity in mammals or in the environment. The Research Objectives have not identified a sufficient body of evidence to make a risk assessment feasible for this nanomaterial.

7.5 SUMMARY
The precautionary principle requires that there is a preliminary scientific evaluation showing reasonable grounds for concern that the nanomaterial might lead to damaging effects on the environment, or on human, animal or plant health. For the majority of the identified nanomaterials, the body of evidence identified was not sufficient to suggest that the nanomaterials will cause harm and therefore the precautionary principle should not be considered in these cases. However, three different nanomaterials have been identified that give rise to sufficient concern from the results presented within the Research Objective reports. There is evidence that carbon nanotubes may have an adverse effect on human health; and that silver nanoparticles and titanium dioxide nanoparticles are detrimental to the environment. In these specific cases further investigation as to the need to invoke the precautionary principle is required, taking into consideration all available data.