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Nanotechnologies

8. Are current risk assessment methodologies for nanoparticles adequate?

  • 8.1 What considerations should the risk assessment take into account?
  • 8.2 What factors of exposure do risk assessment methodologies need to specify?
  • 8.3 How should risks and hazards related to nanoparticles be addressed?
  • 8.4 What should be done to improve the risk assessment of nanoparticles?

The SCENIHR opinion states:

3.10.1 Introduction

Nanoparticle forms of various chemicals (metals, carbon, other inorganic and organic chemicals) are being developed to produce new products that have properties that are qualitatively or quantitatively different from their other physical forms. It would not be surprising, therefore, if their interactions with and in biological systems are also altered. This section addresses the methodologies that may be used to assess the risks to man and the environment arising from the normal manufacture, use and disposal of nanotechnology products. It is recognised that the release of nanoparticles may be associated with abnormal events such as an explosion, spillage or equipment malfunction, but these are not considered further in this Opinion since these were not included in the questions asked of SCENIHR.

The first issue to consider in any discussion of the methodology required to assess the risks from nanoparticles to man or to the environment is the size range, shape and composition of the nanoparticles. For the purposes of this discussion a nanoparticle is considered to be a particle of 100 nm or less (in either a solid or liquid form) to which humans or the environment may be directly or indirectly exposed. In principle, nanoparticles can be manufactured from almost any chemical. However, the majority of the current limited evidence on the behaviour in biological systems is mainly limited to transition metals, silicon, carbon (nanotubes, fullerenes) metal oxides and a few agents that have been selected as potential delivery systems for pharmaceutical agents. Before addressing the possible risk to humans and the environment from nanoparticles it is necessary to summarise how their biological properties could differ qualitatively or quantitatively from those of chemical and biological substances in other physical forms. Three situations may be distinguished. The hazard is due a) solely to the substance being in nanoparticle form, b) principally to the chemical composition of the particle and c) combination of a) and b) It should be noted that because of the restricted range of nanoparticle types whose biological properties have been studied to date, it is uncertain whether or not the findings are representative of nanoparticles in general. The possible stages in the fate of a nanoparticle once released are set out in Figure 3.

Source & ©: SCENIHR  The appropriateness of existing methodologies to assess the potential risks associated with engineered and adventitious products of nanotechnologies (2006),
3.10 Risk Assessment Methodologies, p. 41

3.10.4 Scope of Nanoparticle Risk Assessment

If there is a potential for exposure of humans, other species or the environment to free nanoparticles from a product or process, including disposal processes, some form of risk assessment is required. This is necessary regardless of whether or not the toxicology of the chemical(s) comprising the nanoparticle is well established.

The factors that need to be considered in the risk assessment of a new form of nanoparticle associated with a product or process are set out in Figure 5.

Depending on the conditions of manufacture, formulation, use and final disposal, a risk assessment of nanoparticles may need to address:

  • Worker safety during the manufacture of nanoparticles. It is noted that typically workers are exposed to higher levels of chemicals and for more prolonged periods of time compared to the general population and this will probably be the case for nanoparticles production.
  • Safety of consumers using products that contain nanoparticles.
  • Safety of local human populations due to chronic or acute release of nanoparticles from manufacturing and /or processing facilities.
  • The impact on the environment per se resulting from production, formulation and use, and on the potential for human re-exposure through the environment. Particular attention is required for products that are deliberately used in nanoparticle form in the environment, e.g. biocides, environment improving agents.
  • The environmental and human health risks involved in the disposal or recycling of nanoparticle dependant products. This includes the potential for nanoparticles to escape from ‘contained’ waste disposal sites as well as their impact on sewage treatment plants.

One or more of these risk assessments may be omitted if there are valid reasons to conclude that that no exposure will occur. In principle, the traditional risk assessment procedure is an appropriate tool for assessing the risks from exposure to nanoparticles under specified exposure conditions. However it has to be recognized that the public expectation of new or emerging technologies is that higher requirements for safety are needed than for tried and tested technologies. Failure to meet the expectations may result in public fear or even rejection of nanotechnology based products.

The traditional risk assessment methodology comprises the following stages:

  1. Exposure assessment
  2. Hazard identification
  3. Hazard characterization
  4. Risk characterization

This framework has not yet been applied to nanoparticles generally either in terms of their potential human or environmental impacts for a number of related reasons. There is an unclear situation in regard to regulatory requirements for risk assessment. As a consequence there are no official guidelines on what constitutes an appropriate testing regimen. The manufacture of nanoparticles commercially is relatively new and there is very limited relevant epidemiology or environmental monitoring data available. The focus has been on production expressed as mass (COM 67/548, see REACH for example) rather than particle size; this may severely underestimate the potential contribution of nanoparticles to overall risk posed by the substance.

It is evident from the foregoing discussion that there is already sufficient data to conclude that, from a risk assessment point of view and for some types of nanoparticle at least, it is not valid to rely entirely on toxicological findings from testing the component of a nanoparticle of interest in another physical form.

Three situations may be distinguished:

  1. A substantial amount of good quality human and environmental hazard and exposure information on the substance (in its ‘conventional’ form) that comprises the nanoparticle of interest already exists. In this case the question is what further information is required to supplement this in order to provide the necessary confidence in the safety of the nanoparticle product. It must be reiterated that it is not scientifically valid to rely exclusively on the properties of the chemical in other physical forms for risk assessment purposes.
  2. The substance has already been produced in a one form of nanoparticle. A new form of nanoparticle is then produced. Is it necessary in this case to repeat all the studies required by i) for this new particle form?
  3. Limited or no information is available on the biological properties of the substance that comprise the nanoparticle. The question that needs to be addressed in this case is what is the full package of tests that needs to be conducted assuming that human and environmental exposure will only be to its nanoparticle form.

In the following text the emphasis is on the first situation, namely where there is accessible suitable data on the human and environmental hazards of the substance that comprises the nanoparticle.

Source & ©: SCENIHR  The appropriateness of existing methodologies to assess the potential risks associated with engineered and adventitious products of nanotechnologies (2006),
3.10.4 Scope of Nanoparticle Risk Assessment, p. 46

8.1 What considerations should the risk assessment take into account?

The SCENIHR opinion states:

3.10.2 General Exposure Considerations

Route of exposure is the first consideration in developing the methodology to be used . Much of the published human toxicological and epidemiology data relates to airborne exposure. However there is a variety of additional routes by which man can be exposed to nanoparticles that may need to be considered including:

  • Ingestion (foods, food additives and contaminants, various medicinal agents)
  • Topical contact (surface finishing products, contaminants, cosmetics)
  • Injection or implantation (some medicinal products)

Based on the information provided in the previous sections, it is evident that particle size may influence the biological properties of a substance in a number of different ways. With respect of exposure there is evidence that nanoparticles may be able to penetrate cell membranes and thereby enter various cell types, whereas larger particles may be excluded. If a nanoparticle can penetrate cell membranes, it may be assumed that nanoparticles have the potential to reach other organs in addition to those which are the portals of entry.

Most of the work on this topic is being conducted by the pharmaceutical industry because of the potential to improve drug delivery to target tissues. There is very little information in the published literature on how nanoparticles may be distributed within cells once absorbed. There is some evidence that titanium dioxide nanoparticles are widely distributed in cells and are not necessarily membrane bound. In another study on endothelial cells using nanoparticles of poly DL lactide-co-glycolide polymer containing serum albumin, concentration of the nanoparticles was shown in the cytoplasm (Davda and Labhasetwar 2002). The extent to which the distribution is substance-specific is unclear. There is evidence that airborne nanoparticles, in contrast to larger particles, are able, via the nose, to pass along the olfactory nerve and enter the brain (Oberdörster G et al, 2004b). Following their ingestion, nanoparticles may be taken up by the Peyers patches in the intestine. It is not known how well absorbed nanoparticles can penetrate the fenestrated capillaries.

To date there is no good evidence of a specific particle size, shape and surface charge at which altered penetration of cell membranes occurs. It is very important from a risk assessment viewpoint to understand whether the relationship between particle size and effect, indicated in Figure 4, is best represented by:

  • a sigmoid curve, or
  • involves a sharp change. It is biologically plausible that as the particle size reduces, a sudden increase in absorption and/or toxicity arises. It is important to establish whether this is the typical situation or specific to certain nanoparticles. In the absence of adequate data to the contrary, this particle size response model should be used as the default position.

It has also been found that for certain nanoparticles the clearance mechanisms may be less effective than that for larger particles. For example, impaired phagocytosis has been observed in a macrophage cell line containing nanoparticles (Renwick et al 2001). If this finding reflects a more general phenomenon, nanoparticles would need to be considered to have the potential for bioaccumulation in humans and possibly in other species and in the environment.

There have been even fewer studies on the behaviour of nanoparticles in the environment. It is probable that nanoparticles in ambient air will be widely dispersed unless they react with other components in the air. It needs to be established whether nanoparticles of a chemical, by virtue of their size and surface properties, may partition and distribute differently in the environment compared to other physical and chemical forms, for example (see Figure 3). It is also vital to establish whether or not there is a tendency for substances in nanoparticle form to be more or less persistent in the environment than larger sized counterparts.

What is clear from the published literature on human toxicology is that the expression of the exposure dose in terms of unit weight, which is the established practice in toxicology, is often not appropriate when studying the toxicity of nanoparticles. Instead either total surface area, or number of particles, or a combination of surface area and number of particles, should be used.

3.10.3 Hazard Considerations

In view of the potential for nanoparticles to penetrate proteins, nucleic acids and other biological molecules, it is possible that unique adverse effects never previously observed for chemicals in other physical forms could occur. There is no evidence that this is the case in practice. However, the methodology to evaluate the hazards needs to incorporate the possibility.

The main source of information on the potential for adverse human health effects with nanoparticles are the epidemiological studies of airborne particles in ambient air. These have shown that smaller particles of low solubility (less than 1µm) are substantially more toxic than larger particles. In part this is due to the fact that the dose in particle number terms is much higher per unit weight for small particles. There is evidence that these particles also penetrate the alveolar cell barrier more effectively than larger particles. It should be noted that the majority of studies to date have been confined to particle sizes from 0.1 to 10 µm. The size of airborne particles has also been reported to influence perceptions of adverse effects. For example Keady and Halvorsen (2000) have shown that the airborne level of nanoparticles in offices correlates directly with complaints of sick building syndrome. It has been found that as far as ambient air pollution with fine particles is concerned, there is a population subgroup that is much more sensitive to the adverse effects than the public as a whole. This subgroup includes individuals with severe chronic respiratory and heart disease. Whether the same population would be much more sensitive to other forms of airborne nanoparticle is uncertain but this must be considered to be a real possibility.

There is little information on trends in species differences in either the toxicokinetics or toxicodynamics of nanoparticles and a cautious approach must be adopted in the extrapolation of findings in animals to man. There is some evidence from published animal studies that nanoparticles can have a greater toxicity or, perhaps, a different toxicity compared to larger particles of the same substance. Lam et al (2004) and Warheit et al (2004) have published the results of studies of the toxicity of single-wall carbon nanotubes in mice and rats respectively. Using an intratracheal route of administration they compared different means of nanotube production with effects of carbon black and quartz particles. In the Lam et al study the nanotubes were found to produce dose dependent lung lesions. The effects of carbon black were distinctively different. The study by Warheit et al was more comprehensive. It showed multifocal pulmonary granuloma but without evidence of ongoing pulmonary inflammation or cellular proliferation. These effects are different from those of quartz, carbon black and graphite. The conclusion from these two studies is that carbon nanotubes have different toxicological properties from other forms of carbon (Dreher 2004). This supports the case for a separate/ additional risk assessment of substances that are in nanoparticle form.

These differences may be attributable to the fact that they have a much greater surface area to weight ratio than larger particles and, as a consequence, they tend to be more chemically reactive and bind other substances to their surface more effectively.

Source & ©: SCENIHR  The appropriateness of existing methodologies to assess the potential risks associated with engineered and adventitious products of nanotechnologies (2006),
3.10.2 General Exposure Considerations, p. 42

8.2 What factors of exposure do risk assessment methodologies need to specify?

The SCENIHR opinion states:

3.10.5 Exposure Assessment Methodology

An algorithm is provided in Figure 6 setting out the key steps in the exposure assessment. Methodology is required to identify how nanoparticles distribute in environmental compartments and in human tissues.

Risk assessment may be applied either to a chemical (or a mixture of chemicals) in nanoparticle form and/or to a product in which this nanoparticle form is incorporated. The former approach has the benefit that if the identified risk is deemed to be acceptable, the risk assessment of the products in which it is incorporated can be restricted, unless there are reasons to assume that the exposure or the toxicology may be significantly different due the other components of the product. In the discussion below the term product is used for both the chemical itself and any item it may be incorporated in.

It is important for risk assessment purposes to specify clearly at the outset the following factors.

Product specification (physical chemical properties)

The amount that is expected to be produced along with the anticipated uses and proposed routes for disposal/recycling of the product(s) at the end of its useful life. Is probable that different manufacturers will produce nanoparticles of rather similar chemical composition that are not identical in all their properties. It is therefore vital that the specification of the nanoparticle form is thorough and comprehensive. The description should include:

  • The chemical composition of the nanoparticle including formulation components and impurities, surface chemistry, acidity/basicity, redox potential, reactivity (redox, photoreactivity etc.) and the nature of any surface coating or adsorbed species.
  • The particle size range (and distribution) to which humans and/or the environment will be exposed, along with information on other physical characteristics, e.g. shape, density, surface area and charge, solubility, porosity, roughness morphology, crystallinity and magnetic properties. Note that the nature of the nanoparticle to which organisms or individuals are exposed may differ, for example between workers, consumers and the environment and might also differ from the particle size distribution in the product itself (NB This size range must also have been used in hazard assessment tests).
  • The extent to which the released particles are soluble in aqueous media, and/or biodegradable. This is likely to be a major factor in limiting their accumulation and persistence in man and the environment.
  • Their chemical and physical stability under relevant environmental conditions including potential for coalescence and/or degradation (along with the identification of the degradation products).

Intended use along with the identification of each of the likely exposure scenarios (including potential for accidental exposure)

  • Both normal and high level use situations need to be identified in order to assess emission routes, levels and duration of human exposure and the release and distribution in the various environmental compartments. This may need to include possible misuses and accidents that could result in substantial human and /or environmental exposure although this is beyond the scope of this Opinion.
  • Potential methods of disposal of the product at the end of its use and the exposure consequences for the environment should be considered.

Examination of human exposure

  • Identification and quantification of relevant exposure.
  • Determination of the absorption of the nanoparticle by the appropriate route(s) of exposure at relevant doses and dose rates, including all possible translocation routes.
  • Identification of the metabolic fate. This includes the characterisation and quantification of nanoparticles in body tissues.
  • Examination of the potential for bioaccumulation following repeated exposure to the nanoparticles.

If there is good data on the uptake, metabolism, distribution and excretion of the substance in other physical forms it may be sufficient to demonstrate that uptake and clearance is comparable for the nanoparticle form using the appropriate route of exposure. If this is demonstrated, then only limited hazard identification and characterisation may be needed.

Examination of environmental exposure

  • Identification and quantification of relevant exposure
  • Determination of the environmental release pattern (and quantities), the distribution (including the mobility and specific ‘sinks’) and fate (including persistence) of the nanoparticle in the various environmental compartments. For metal and metal oxide nanoparticles assessment of the dissolution rates and speciation in the environmental compartment will be key to understanding the fate and ultimately the bioavailability of the substance. Attention should be given to those nanoparticles that are designed to be deliberately released into the environment (for example agents used to clean up chemical spillages) and the waste products of nanotechnology.
  • Establishment of concentrations (calculated and/or measured), in terms of particle surface and or number, in the different environmental compartments.
  • Examination of the potential for bioaccumulation in different aquatic and terrestrial species and possibly the potential for biomagnification in the different environmental compartments.

Data demonstrating that the above processes and characteristics of the nanoparticle are similar to that of the conventional substance may lead to a reduction of data needs for the risk assessment.

Summary

It is unclear at the present time the extent to which the toxicokinetics, the environmental distribution and fate of nanoparticles can be predicted from knowledge of their physicochemical properties. In view of the limited range of substances as yet produced in nanoparticle form and the potential for most chemical substances or mixtures to be produced in this form, caution needs to be used in extrapolation from published data.

A particular concern is the potential for persistence of nanoparticles in humans and the potential for bioaccumulation in the environment. In humans, and other species, there is concern as to whether the clearance mechanisms for larger particles are as efficient in dealing with nanoparticles. In the environment there is concern of the possible differences in distribution of nanoparticles both in air, aquatic and terrestrial compartments.

Source & ©: SCENIHR  The appropriateness of existing methodologies to assess the potential risks associated with engineered and adventitious products of nanotechnologies (2006),
3.10.5 Exposure Assessment Methodology, p. 48

8.3 How should risks and hazards related to nanoparticles be addressed?

The SCENIHR opinion states:

3.10.6 Hazard Identification and Hazard Characterization Methodology

It is assumed that the range and type of adverse effects that could arise from exposure to nanoparticles is likely to be similar to that identified for chemicals in other physical forms. If this assumption is correct, there would be no reason to change existing well established toxicity testing protocols. If it is not, additional endpoints may need to be considered for the toxicological assessment of nanoparticles.

A number of mechanisms by which nanoparticles may exert toxicity have been proposed and these are summarised in Figure 7. The critical issue to be resolved is whether the hazard is due principally to;

  • the toxicological properties of the chemical(s) that comprise the core of the nanoparticle,
  • the much greater relative surface area of the nanoparticle form and, consequently, the greater potential reactivity, or
  • the potential, due to the enhanced surface area and possible surface reactivity, for other chemicals of concern to be absorbed onto the nanoparticles.

In reality, a combination of these factors may be expressed. In the case of a), similar properties to the chemical in other physical forms could be anticipated. However, if the distribution of the nanoparticles in the human body or in environmental species is very different, this may result in altered toxicological profile. In the case of b) and c) the nanoparticle form would be anticipated to have altered toxicological properties. If chemicals of toxicological concern are likely to be adsorbed onto nanoparticles, the potential for the release of these chemicals will need to be addressed.

With chemicals for which the toxicology is well documented and where the toxicokinetics of the nanoparticle form are similar to those of the chemical in other physical forms, a screening test battery could be introduced to establish whether b) or c) are significant to the hazard profile.

This test battery could comprise mainly in vitro and chemical tests. However, no appropriate tests are currently available.

With those chemicals for which the toxicological properties of other physical forms are well established, a testing strategy (screening) is needed that will identify whether or not the nanoparticle form will or will not cause significantly different adverse effects. The proposed approach is set out in Figure 8. The selection of this test battery should be informed by knowledge of the chemical, physical and biological properties, along with data on the same chemical in other physical forms. In vitro tests could in principle play an important role in this screening process. If there are substantial differences between the nanoparticle form and other physical forms of the chemical, then the regulatory guidelines for testing of a new chemical/ particular type of product for its effects on human health and on the environment should be followed. (EU Technical Guidance Document, European Commission 2003 ).

At this stage in establishing the knowledge base for nanoparticles, it would be helpful to bench mark studies against substances with very well understood toxicology in man, such as quartz and asbestos.

In principle in vitro studies combined with information on the surface chemistry could provide an important early indicator of the differences or similarities in potential hazard between the nanoparticle form of a substance and other physicochemical forms. However, characterisation of the uptake, distribution, deposition and retention of nanoparticles and the comparison with their larger size counterparts may require an in vivo approach.

3.10.7 Risk Characterization and Integrated Risk Assessmen

As discussed above the presentation of a chemical(s) in nanoparticle form may result in changes in both exposure (including environmental fate and persistence, uptake, metabolism, clearance and bioaccumulation) and the nature and magnitude of the adverse effects. Due to the lack of available data on the risk characterisation of different nanoparticle-based products, no generic conclusions are possible at this stage. Consequently, each product and process that involves nanoparticles must be considered separately in terms of:

  • Worker safety during the manufacture of nanoparticles.
  • Safety of consumers using products that contain nanoparticles.
  • Safety of local populations due to chronic or acute release of nanoparticles from manufacturing and /or processing facilities.
  • The impact on the various environmental compartments per se resulting from production, formulation and use, and on the potential for human re-exposure through the environment.
  • The environmental and human health risks involved in the disposal or recycling of nanoparticle dependant products.

In the absence of suitable hazard data a precautionary approach may need to be adopted for nanoparticles which are likely to be highly biopersistent in humans and/or in environmental species. It should also be noted that there is no reliable information on the effect of the simultaneous exposure to multiple forms of nanoparticles, where it would be appropriate to assume the effects are.dditive, or on the interaction between nanoparticles and other stressors (either physical, chemical or biological), which should be considered on a case-by-case basis.

Source & ©: SCENIHR  The appropriateness of existing methodologies to assess the potential risks associated with engineered and adventitious products of nanotechnologies (2006),
3.10.6 Hazard Identification and Hazard Characterization Methodology, p. 51

8.4 What should be done to improve the risk assessment of nanoparticles?

The SCENIHR opinion states:

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.

3.10.11 Conclusions

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.

Source & ©: SCENIHR  The appropriateness of existing methodologies to assess the potential risks associated with engineered and adventitious products of nanotechnologies (2006),
3.10.8 Critical gaps in knowledge required for risk assessment purposes, p. 54


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