3.10.8 Critical gaps in knowledge required for risk assessment purposes
There is a paucity of information in a number of areas that are fundamental to the development of detailed guidelines on the risk assessment of nanoparticles. These include:
- Protocols need to be established that enable the release of nanoparticles from a very wide range of production processes, formulation and use of products to be assessed
- Whether it is possible to extrapolate from the toxicology of non-nano sized fibres, particles and other physical forms of the same substance to nanosized materials, and between nanoparticles of different size ranges.
- The actual measured range of exposure levels (to man and the environment) experienced during use of nanoparticle based products. This will require the development of new measurement techniques for routine use.
- Information on the health of workers involved in the manufacture and processing of nanoparticles, since this group may receive the greatest exposure to engineered nanoparticles.
- Information and measurement of environmental fate, distribution and, persistence (including bioaccumulation) of nanoparticles
- Effects of nanoparticles on various environmental species of each of the environmental compartments and representative of different trophic levels and different exposure (uptake) routes.
- There is a lack of background data on the current and historic exposure of humans and environmental species to nanoparticles. Such information is important to the assessment of a possible additional risk from exposure to nanoparticles arising from the development of nanotechnologies.
- Information on the possibility that simultaneous exposure to different particles could result in additive effects.
3.10.9 Regulatory and Other Aspects Related to Risk Assessment
The regulation of products containing nanoparticles based on tonnage, as proposed for existing chemicals under REACH, needs to be considered further because there are many more nanoparticles to the tonne than is the case for larger particles, and their behaviour in the body and in the environment may be different. If the nanoparticle form of a chemical does have distinctly different properties in biological systems from other physical forms of the same chemical, it will be necessary to readily identify the nanoparticle form of each chemical for the purposes of hazard warning labels etc. One approach to ensure that the effects of the nanoparticle form of a chemical is properly assessed would be to have a unique identification for it, either assigning different CAS numbers to the nanoparticle form, or adding a code (CAS-NP50) to existing CAS numbers leaving the CAS number for identifying similar chemical compounds .
It is also inappropriate to assume that current workplace exposure standards for dusts can be applied directly to the nanoparticle form of the dust component. New standards will therefore need to be considered. Similarly, classification and labelling for human health and the environment may need to be reconsidered.
3.10.10 Other Needed Developments
In order that nanotechnology and nanomaterials can be developed responsibly, with optimization of benefits and minimization of risks, international cooperation on identifying and resolving gaps in knowledge is required. It is recognized that a major barrier to progress in this area is the confidential nature of much of the research on nanoparticles. Means of facilitating co-operation with industry to fill some of the critical knowledge gaps for risk assessment purposes need to be found to avoid the experience of the biotechnology industry of public perception of the risks.
There is an urgent need for a harmonized terminology/ nomenclature for defining the physical characteristics of nanoparticles and their general properties. For the further development of risk assessment, standardisation of testing methodologies is needed to identify exposure scenarios and potential hazards of nanoparticles. In addition, the availability of reference materials would be of high importance to function as benchmark for adverse effects.
A transparent framework for risk benefit analysis should also be developed that is able to achieve wide acceptability.
There is insufficient data available to identify any generic rules governing the likely toxicology and ecotoxicology of nanoparticles in general.
In the absence of data to the contrary it cannot be assumed, for risk assessment purposes, that the nanoparticle form of a chemical(s) has similar effects on biological systems to those of the same chemical in other physical forms. To maintain a high level of public health, occupational health and environmental protection in the European Union, it is essential that a specific risk assessment is conducted along the lines proposed above if there is any potential for humans and the environment to be exposed to particular forms of nanoparticles.
Exposure dose needs to be defined in terms of number of particles and/or total surface area rather than the conventional use of mass. Change in the size/shape and other physicochemical properties of a nanoparticle could result in changes in the adverse effects. Therefore it is essential to specify the precise size and other characteristics of each nanoparticle product in order to conduct a reliable risk assessment.
A framework is proposed that enables both human and environmental risk assessment to be targeted and avoids unnecessary testing.
A number of the conventional toxicity tests may require some modification for the assessment of nanoparticles in order to ensure that the exposure conditions simulate realistic exposure scenarios and that endpoints are directly associated with the nanoparticles to be assessed.
These conclusions have very important regulatory implications.
3.11 Prioritisation of Needs in Knowledge
In general, and in spite of a rapidly increasing number of scientific publications dealing with nanoscience and nanotechnology, there is insufficient knowledge and data concerning nanoparticle characterisation, their detection and measurement, the fate (and especially the persistence) of nanoparticles in humans and in the environment, and all aspects of toxicology and environmental toxicology related to nanoparticles, to allow for satisfactory risk assessments for populations and ecosystems to be performed.
The major gaps in knowledge that need to be filled in relation to improved risk assessment for the products of nanotoxicology include the following. These are cited in a logical order starting with nanoproduct manufacture through human and environmental exposure to the toxicology and fate of nanoparticles. All of these areas require urgent attention. However, it is emphasised that the area in most need of attention is that concerned with the identification of exposure levels, both to man and the environment, which will require new and modified measurement techniques.
- The characterisation of the mechanisms and kinetics of the release of nanoparticles from a very wide range of production processes, formulations and uses of the products of nanotechnology.
- The actual range of exposure levels, both to man and to the environment, experienced during use of nanoparticle based products.
- The extent to which it is possible to extrapolate from the toxicology of non- nano sized fibres, particles and other physical forms of the same substance to the toxicology of nanosized materials.
- Toxicokinetic data following exposure at various portals of entry, so that target organs can be identified and doses for hazard assessment determined. This includes dose response data for the target organs, and knowledge of the subcellular location of nanoparticles and their mechanistic effects at the cellular level.
- Information on the health of workers involved in the manufacture and processing of nanoparticles.
- The fate, distribution and, persistence (including bioaccumulation) of nanoparticles in the environment.
- The effects of nanoparticles on various environmental species, in each of the environmental compartments and representative of different trophic levels and exposure routes.