Nanomaterials

1. How far has risk-assessment of nanomaterials developed?

Over the last few years, there has been an increase in awareness of the potential risks associated with manufactured nanomaterials. Legally, manufactured nanomaterials are covered by the definition of substances5 as mentioned in the REACH legislation (Regulation (EC) No 1907/2006) (European Commission 2006). Risks associated with substances have to be evaluated according to various EU regulations depending on product category and production volume. A review of the European Community legislation in relation to nanomaterials has recently been finalised (COM/2008/0366 final) (European Commission 2008). The main conclusion was that the current legislation does cover in principle the potential health, safety and environmental risks in relation to nanomaterials. The protection of health, safety and the environment needs mostly to be enhanced by improving implementation of current legislation. In addition, it was concluded that the knowledge on essential questions such as characterisation, hazards, exposure, risk assessment and the risk management of nanomaterials needs to be improved (European Commission 2008).

To date, the SCENIHR has published three Opinions dealing with various aspects of the possible risks of the use of nanotechnology in all aspects of society. The first Opinion dealt with the risk assessment methodologies available for evaluating the possible adverse health and environmental effects of nanotechnology products (SCENIHR 2006), while the second and third described more technical aspects on how to properly investigate the safety of nanomaterials when using the Technical Guidance Documents for the evaluation of dossiers of chemical substances (SCENIHR 2007a), and what definitions within the nanotechnology area can be used for risk assessment (SCENIHR 2007b). It must be noted that nanotechnology has introduced new nanoparticulate forms of chemicals, of which properties, behavior and effects are largely unknown, and, hence, of concern. Although only two years have passed since the first evaluation of possible risks of nanotechnologies, there has been substantial activity in the evaluation of the harmful effects of nanomaterials, notably in the evaluation of potential toxic effects of nanomaterials by in vitro assays. Currently, in vitro assays are useful for screening purposes and may provide valuable insights into the underlying mechanisms of adverse effects. However, in vitro assays have their limitations, especially in relation to evaluation of a possible risk for humans and the environment. Therefore, at present, in vivo assays are still needed for risk assessment.

An important issue of appropriate safety evaluation is the choice of an exposure dose in the test system that is relevant for human or environmental nanomaterial exposure. In addition, there are still some uncertainties about the best dose metric to be used in safety evaluations and the risk assessment of manufactured nanomaterials.

Another lack of current safety evaluation of nanomaterials is the fact that most in vitro and in vivo studies are only short-term while impacts on human health and the environment are more likely to occur during and after long-term exposure. Consequently, there is an urgent need for long-term exposure studies.

There are indications that there is a steady increase in products produced by nanotechnology or containing nanomaterials that are available on the market. The inventory of the Woodrow Wilson International Centre for Scholars now contains almost 800 consumer products with a nanotechnology claim (WWICS 2008). A major drawback of this registration is that it is based on voluntary information and claims from the manufacturers, which in many cases cannot be verified.

As a matter of example, one of the nanomaterials that has been increasingly applied is nanosilver, reported to be present in a great variety of products such as washing machines, socks, food contact material, wound dressings and food supplements (Wijnhoven et al. 2009, WWICS 2009). The possible use of nanoformulations for food supplements must be looked at carefully as it may be regarded either as potentially hazardous (EFSA 2008) or as potentially beneficial depending on the specific case. Increased bioavailability due to the nanoformulation of the supplement may be beneficial for some applications but may create the possibility of overdosing.

In fact, when nanomaterials are firmly embedded in large structures, for example in electronic circuits, they are less likely to escape this structure and no human or environmental exposure is likely to occur. However, while this may be true during production and appropriate use of nanomaterial-containing products, exposure may occur during abuse, waste and recycling. In other words without any exposure there is no risk. Hence the estimation of exposure scenarios in terms of their frequency, their quantity and quality, and their targets (individuals, populations, etc.) are absolutely mandatory for a rational risk assessment. It should be realised that (especially for inhalation exposures) exposure to particulate matter may be due to natural and accidentally induced nanoparticles (i.e. particulate air pollution by combustion processes). Based on discussions in OECD and ISO working groups, a consensus is now emerging on the physical-chemical properties of nanoparticles that need to be addressed in the risk assessment process of nanomaterials (OECD 2008a). It should be noted that these properties should also be determined for the nanomaterials as used in the testing for safety evaluation, and not only on the nanomaterials as provided by the manufacturer. For most nanomaterials, a full evaluation of potential hazards has not yet been performed. Recently, the OECD has started a sponsorship programme in which, for 14 of the most used nanomaterials, a dossier on hazard identification will be produced (OECD 2008a). The programme contains an extensive list of endpoints to be determined including those for nanomaterial information/identification, physical-chemical properties, as well as material characterisation, environmental fate, environmental toxicology, mammalian toxicology, and material safety (OECD 2008a). For this evaluation, current OECD guidelines and other tests will be used. One of the outcomes of this programme will be insights into the suitability of the current OECD guidelines for hazard identification and where adaptations of these guidelines will be needed specifically for manufactured nanomaterials. This will contribute to the design of a testing strategy.

This Opinion deals with the recent developments in the area of risk assessment of nanomaterials. Some specific hazards have been identified which will be discussed in the context of risk for human health. These include developments in the understanding of toxicokinetics of nanomaterials, the possibility of nanoparticles to induce protein fibrillation, the possible pathological effects of specific types of carbon nanotubes, genotoxicity and size effects. Knowledge is becoming available on the behaviour of nanoparticles in the environment in terms of the development of possible fate scenarios. In addition, effects on environmental organisms have been demonstrated. The staged approach to the risk assessment of human and environmental risks as presented in a previous Opinion of SCENIHR (SCENIHR 2007a) will be elaborated on further.