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Nanotechnology and manufactured Nanomaterials:Opportunities and Challenges

IFCS Forum VI

THOUGHT STARTER1

Objective of the plenary session:

The objective is to exchange information in order to help raise the awareness of participants to the potential new opportunities, the new challenges and the new risks posed by nanotechnology.

The meeting will provide a forum to share information on known and emerging issues, on the work of the OECD, ISO and UNESCO on nanotechnology and to foster an understanding of issues (applications and implications).

The Forum will also be an opportunity to discuss the potential contributions of nanotechnology to sustainable development and pollution prevention, and to discuss how to achieve an equitable distribution of benefits and risks and role of responsible stewardship in addressing nanotechnology.

1 Thought Starter papers are intended to provoke thought and bring about discussion. Thought Starter papers are not an in depth analysis or comprehensive review of the topic.

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Table of Contents:

1 Background........................................................................................................................32 Ethical considerations........................................................................................................43 Social utility of nanotechnology........................................................................................44 The state of the knowledge about the risks of nanomaterials............................................55 Communication and public dialogue.................................................................................56 Activities of International Organisations...........................................................................67 Activities of non-governmental organizations...................................................................78 National activities, interests and priorities on nanotechnology and manufactured nanomaterials..............................................................................................................................8

Belarus....................................................................................................................................8China.......................................................................................................................................9European Commission............................................................................................................9Germany...............................................................................................................................14Korea....................................................................................................................................15Nigeria..................................................................................................................................16Slovenia................................................................................................................................16Switzerland...........................................................................................................................17Thailand................................................................................................................................18United Kingdom...................................................................................................................19

9 Annex...............................................................................................................................209.1 Definitions and types of manufactured nanomaterials............................................209.2 Health risks..............................................................................................................219.3 Occupational health.................................................................................................229.4 Environmental risks.................................................................................................239.5 Ethical issues...........................................................................................................24

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1 Background

Nanotechnology is an enabling technology that is expected to result in major changes across many industry sectors and to contribute to novel materials, devices and products. Depending on the area of application there are different timelines for the beginning of industrial prototyping and nanotechnology commercialization. First generation products are already on the market such as paints, coatings and cosmetics. More products such as pharmaceuticals, diagnostics and applications in energy storage and production are in development. Many studies have tried to estimate the prospect of the nanotechnology market with different data. In general the areas of nanoelectronics (semiconductors, ultra capacitors, nanostorage and nanosensors) are estimated to be around 450 billion $ for 2015, and the areas of nanomaterials (particles, coatings and structures) are estimated to account for 450 billion $ in 20102. Further generations of nano-enabled products based on active nanoscale structures and nanosystems will be developed in the future. Such developments will address innovations looking into processes of technical modernization and changes in the interface between humans and machines/products. Presently discussion on opportunities and challenges of nanotechnology and manufactured nanomaterials focuses on 1st generation nanoproducts. It is incumbent on governments to develop a regulatory framework which enables the responsible introduction of manufactured nanomaterials through the scientific assessment and appropriate management of the potential risks. The thought starter gives an overview of the topics relevant for this discussion. The scope does not include the area of medical diagnostics and treatment as this is being addressed in other fora.

Nanotechnologies and manufactured nanomaterials, as with any new technology, may bring many advances to society and benefits for the environment, but also pose new challenges in health, environment safety and possible impacts on society. Because of the very broad range of potential applications using nanotechnology and the wide variety of characteristics displayed by manufactured nanomaterials, detailed discussion of both benefits and of heath and environmental risks should take place at the level of individual nanotechnology applications. As a result of nanotechnology’s rapidly burgeoning growth, it is important that all stakeholders concerned (governments, international, regional and national organizations, industry groups, public interest associations, labour organizations, scientific associations and civil society) engage in discussions to identify and address policy issues. These can include health, safety, moral, ethical, societal, legal and social utility concerns. In view of the predicted great impact of nanotechnologies on the global economy, research and society, and of the expected wide-spread use of nanomaterials, any possible risks should be studied by comprehensive, proactive risk estimation and assessment.

The nanotechnology agenda item at IFCS Forum VI is to provide an overview of current work and debates on nanotechnology and inform stakeholders of where these discussions are occurring.

2 Hullmann A. Measuring and assessing the development of nanotechnology; Scientometrics 70(3): 739-758, 2007

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2 Ethical considerations

Only a few ethical committees have explored the ethical challenges posed by this technology. As the Royal Society acknowledged, “These questions are not unique to nanotechnologies but past experience with other technologies demonstrates that they will need to be addressed”3. A number of prestigious reports (e.g. UK Royal Society) and coalitions (labour, environmental, and civil society groups) have advocated for the precautionary approach to apply to development and commercialization of manufactured nanomaterials. The precautionary principle is often discussed in ethical committees. Other issues also identified as priorities for discussion include: agreement on socially acceptable or unacceptable risks, the social and global distribution of benefits and risks, ownership/patent issues, health and safety risks to workers and the public, regulatory oversight, and moratorium on technological applications. These, as well as whether and to what degree a precautionary approach should be adopted, are often discussed in ethical committees (see Annex 8.5).

3 Social utility of nanotechnology

The way in which we use available natural resources has effects on our health and the environment and is to a large part heavily influenced by cultural aspects and personal choices. Natural resources are an important factor in the economy and an important element of our welfare. Technological innovations, including those resulting from nanosciences and nanotechnologies, can play a key role in the more efficient use of our resources.

Before the development or use of any application from nanotechnologies, the question of social utility should be asked. To answer that question the potential contribution of specific applications from nanotechnologies to solve a specific socially relevant problem such as climate change, water shortages and starvation should be known. Health and environmental risks and possible side effects on society and economy should be taken into account as well as existing alternative solutions. The result of such an evaluation will always be a local decision (country, region).

For the majority of developing countries, commodity production is the backbone of the economy4. Historically, advances in science and technology have also had profound impacts on commodity production and trade. There are concerns that nanotechnology will change the commodity markets, disrupt trade and eliminate jobs. Worker-displacement brought on by commodity obsolescence will hurt the poorest and most vulnerable, particularly those workers in the developing world who don’t have the economic flexibility to respond to sudden demands for new skills or different raw materials. Currently, nanotech innovations and intellectual property are being driven mainly from developed countries. The world’s largest transnational companies, leading academic laboratories nanotech start-ups are seeking intellectual property on novel materials, devices and manufacturing processes. Commodity dependent developing countries must gain a fuller understanding of the direction and impacts of nanotechnology-induced technological transformations, and participate in determining how emerging technologies could affect their futures.

3 The Royal Society and the Royal Academy of Engineering: Nanoscience and nanotechnologies: opportunities and uncertainties; 2004, page 84 The Potential Impacts of Nano-Scale Technologies on Commodity Markets: The Implications for Commodity Dependent Developing Countries; Research Papers 4; ETC Group, South Center, November 2005

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There are concerns as well that developed countries will benefit more from nanotechnology and that developing countries will suffer more from potential risks (e.g occupational health and safety standards may be lower, waste management and waste disposal infrastructure may not be adequate for nanomaterials and nano-enabeled products).

4 The state of the knowledge about the risks of nanomaterials

Materials are used at nanometric scale for their new properties. One can expect effects of the same level on health and environment.

Various studies have shown that, because of their small size, unbound nanoparticles can be inhaled and enter the bloodstream via the lungs, disperse throughout the body and penetrate other organs, however it should be noted that many of these studies use instillation rather than inhalation as a way to administer nanoparticles, and generally in a greater quantity dose than reflects actual practical circumstances. It has also been shown that, depending on their properties, some manufactured nanoparticles can be damaging to cells. Little data is available on the toxicology, release, environmental behavior and safety of nanomaterials. Although a few studies have been carried out, not all of their results are meaningful, since many of these investigations were carried out using very high concentrations of particles, and with samples or reference materials that had not been accurately characterized (see Annex 8.2, 8.3, 8.4). Several countries have launched research programmes to reinforce independent risk research (see point 7). Greater coordination of these programs could facilitate more efficient use of time and resources.

In the literature it is often stressed that results for one nanoparticle cannot be generalised to other nanomaterials. This is mainly because the characteristics that influence toxicity have not yet been defined. Standardised test protocols and standardized reference compounds would enable comparisons to be made between the different materials and studies. International organizations such as OECD and ISO and national agencies have established programmes to fill this gap (see point 6).

Based on the scientific and methodological principles currently available, no conclusive requirements for the safety of manufactures nanomaterials can yet be formulated. Nevertheless, safety precautions must be taken based on a precautionary estimation of hazard and exposure risk, as with hazardous materials. As soon as the conditions for evidence-based risk assessments of manufactured nanomaterials are present, existing statutory frameworks need to be assessed, and, where necessary amended, to provide conditions for the safe handling of such materials and of nano-enabled products throughout their life cycle. As more knowledge becomes available, safe handling guidelines can be iteratively formulated and revised.

5 Communication and public dialogue

Broad information on opportunities and risks of nanotechnology and nanomaterials is important for public opinion making. Communication is a key prerequisite for the public engagement with new technologies. This opinion-forming process may leave its mark on the development of technologies and their application. Communication should therefore extend further than the field of manufactured nanomaterials to encompass all of nanotechnologies. It should reflect the current state of social, scientific and political knowledge and of public engagement. Account should be taken of both the promise of nanotechnologies and the public fear or rejection it may create.

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The involvement of industry, authorities and the public in the debate on opportunities and risks must be an integral part of technological development. For an integrated approach, this debate should be as broad as possible and not restricted to individual levels or topics (e.g. scientific, psychological, sociological). A challenge is to communicate information on risks and benefits to enable a public dialogue and informed decisions; the challenge will be even more difficult in developing countries. Dissemination of awareness of possible risks of nanotechnology to the public of developed and developing countries should be coupled with positive aspects of nanotechnology, particularly in development of monitoring tools. It should be noted that nanoparticles are released in large quantities in industrial processes as unintended by-product of combustion, welding, explosions, etc., but their detection is currently very limited, mostly due to the lack of established detection mechanisms and because of lack of awareness of the need for monitoring. Many different ways of detection of nanoparticles of different kind can be foreseen.

6 Activities of International Organisations5

OECD has established under its Chemical Committee a Working Party on Manufactured Nanomaterials (WPMN). It aims to promote human health and environmental safety implications of manufactured nanomaterials in order to assist in their safe development (limited to mainly the industrial chemicals sector). The following eight projects are in the workplan of the WPMN: Development of an OECD Database on Human Health and Environmental Safety (EHS)

Research EHS Research Strategies on Manufactured Nanomaterials (including Occupational

Health and Safety) Safety Testing of a Representative Set of Manufactured Nanomaterials Manufactured Nanomaterials and Test Guidelines. Co-operation on Voluntary Schemes and Regulatory Programmes Co-operation on Risk Assessment The Role of Alternative Methods in Nano Toxicology Exposure Measurement and Exposure Mitigation OECD’s Committee for Scientific and Technological Policy has established a Working Party on Nanotechnology (WPN). Its aim is to look at the responsible development and use of nanotechnology and the potential benefits nanotechnology can bring to society, taking into account public perceptions related to advances in nanotechnology and its convergence with other technologies, without forgetting legal, social and ethical issues. The following projects are in the work plan of the WPN: Statistics and Measurement Impacts and Business Environment International Research Collaboration  Outreach and Public Engagement Dialogue on Policy Strategies The Contribution of Nanotechnology to Global Challenges

5 OECD has prepared for Forum VI a separate information paper on work ongoing and planned at the OECD (IFCS/Forum VI/ 4 INF) and IOMC and ISO have agreed to do so. UNESCO has been invited to provide a separate information paper on its ongoing and planned work and a response is awaited.

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ISO has established Technical Committee 229. Currently the following 3 working groups have been established: terminology and nomenclature; measurement and characterization; and, health, safety and environmental aspects of nanotechnology. 10 work items spread across these three work areas are currently under development.

UNESCO Ethics of Science and Technology Programme6 was created in 1998 with the establishment of the World Commission on the Ethics of Scientific Knowledge and Technology (COMEST) to give an ethical reflection on science and technology and its applications.

This programme aims to promote consideration of science and technology in an ethical framework by initiating and supporting the process of democratic norm building. This approach is founded upon UNESCO's ideal of "true dialogue, based upon respect for commonly shared values and the dignity of each civilization and culture". Awareness raising, capacity building and standard-setting are therefore the key thrusts of UNESCO's strategy in this and all other areas.

UNESCO has invited well-known experts in nanotechnology to discuss the state of the art of nanotechnology, examine the controversy surrounding its definition and explore related ethical and political issues. A 2006 report “The Ethics and Politics of Nanotechnology”7; "outlines what the science of nanotechnology is, and presents some of the ethical, legal and political issues that face the international community in the near future." UNESCO has recently published a book on "Nanotechnologies, Ethics and Politics"8. The aim of the book is to inform the general public, the scientific community, special interest groups and policy-makers of the ethical issues that are salient in current thinking about nanotechnologies and to stimulate a fruitful interdisciplinary dialogue about nanoscale technologies among these stakeholders.

7 Activities of non-governmental organizations

International networks of non-governmental organisations play an important role in supporting governmental actions, distribution of knowledge and facilitating democratic participation in decision-making regarding new technologies, including nanotechnology. The United Nations Environment Programme recognizes NGOs who work on international "Chemicals Management" and many have experience supporting local, national, and international progress on public understanding, technical management, policy development and evaluation of nanomaterials. In addition, NGOs such as the International Society of Doctors for the Environment (ISDE), Friends of the Earth (FOE), professional engineering, medical, scientific and other associations, labour organizations, and others work globally to carry out education and outreach to professionals and the general public, and provide technical support in policy development for countries in all stages of economic development. For example, educational and policy work on nanomaterials was carried out in many countries by ISDE, FOE, ETUC and other organizations who provided workshops, legislative development and review, and both technical and non-technical publications. An informed public is key to sustainable and equitable development in all spheres. NGOs offer a diversity of resources including essential support in policy development and public education. Their role as organizing entities is critical to achieve democratic decisions regarding the equitable development and management of nanotechnology.

6 http://portal.unesco.org/shs/en/ev.php-URL_ID=10581&URL_DO=DO_TOPIC&URL_SECTION=201.html 7 http://unesdoc.unesco.org/images/0014/001459/145951e.pdf)8 http://portal.unesco.org/shs/en/ev.php-URL_ID=10883&URL_DO=DO_TOPIC&URL_SECTION=201.html

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8 National activities, interests and priorities on nanotechnology and manufactured nanomaterials

The following information contributed by a select number of countries is presented to provide a brief introduction to ongoing and planned work as a general indication of some approaches being taken. An OECD document provides detailed information on current/planned activities related to the safety of manufactured nanomaterials in OECD member countries, as well as those non-member countries who are participating in OECD’s work9.

Belarus

Promotion of the use of new technologies including nanotechnologies is a priority in the country, especially in the area of medicine. But currently the evaluation of the risks for human health and the environment from the use of nanotechnologies, nanomaterials and nanoproducts and the associated need to consider preventive measures is not a priority of decision-makers. This is mainly due to the lack of scientific information, relatively limited use of nanotechnologies and nanomaterials at this time, and no apparent evidence of adverse impacts on human health and the environment. On the other hand the growing number of publications indicating a potential negative impact of some nanoparticles on human health and the environment is raising public concern because of the free trade of nanoproducts. There is an urgent need to facilitate scientific research on advantages and disadvantages of nano-materials, technologies and products use. The assessment of risk should be carried out at both the national and international levels. Sharing the information and experiences between countries with different levels of economic development is a high priority. There should be wide dissemination of information that will support the promotion of the use of new technologies for sustainable development and also support the protection of human health and the environment.

According to national legislation new products that can impact negatively human health and environment should include safety information or to be tested to get permission to be sold in the domestic market. There are similar rules covering workers' health protection in case of the implementation of new technologies. Work has been initiated to establish a procedure for the registration of nanomaterials and nanoproducts based on an analysis of existing information.

The main areas for international cooperation are the development of standard procedures for health and safety testing of nanomaterials and products, guidance and standards for occupational health protection, rules for the provision of safety information for products and materials (if it is necessary to label products with nanoparticles to protect consumers rights to know).

9 Current Developments/ Activities on the Safety of Manufactured Nanomaterials, Paris, 28-30 November 2007 http://www.oecd.org/env/nanosafety/This document provides information on current/planned activities related to the safety of manufactured nanomaterials in OECD member countries.  Information was provided by delegations who participated in the 3rd Meeting of OECD's Working Party on Manufactured Nanomaterials.  There are also reports on relevant current activities in other International Organisations such as the ISO. In addition, delegations added a short list of highlights at the top of their submissions to give readers a general idea of key events since the 2nd meeting of the Working Party.  (web accessed 08.02.06)

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China

1. The adjustment of government regulation concerning product classification for medical devices made with nanometer biological materials

According to the notice of the State Food and Drug Administration of China (SFDA) announced a notice (document number 146, 2006), the classification of medical devices made with nanometer biological materials (for example medical instruments made with nanometer metal silver material) will be adjusted from Class II medical devices to Class III medical devices, and they should be subject to the administration of Class III medical devices.

2. The standards on nanotechnologies

Up to date China government has published 15 standards on nanotechnologies, of which 11 are national standards and 4 are industrial standards.

3. Research on the nanotechnology safety

With the rapid development of application fields of nanotechnologies, as has happened in many other countries, the issue of nanotechnologies has given rise to serious public and governmental concern. Researchers from the Chinese Academy of Sciences (CAS) initiated activities to study the environmental and toxicological impacts of manufactured nanomaterials in 2001, including recognition, identification and quantification of the biological and environmental hazards resulting from exposure to diverse nanomaterials/ nanoparticles. Currently, more than 30 research organizations in China have initiated their own research activities studying the toxicological and environmental effects of nanomaterials/ nanoparticles, and techniques of recovering nanoparticles from manufacturing processes.

European Commission10

1. Regulatory developments on human health and environmental safety including recommendations or discussions related to adapting existing regulatory systems or the drafting of laws/ regulations/ guidance materials

The Commission is performing a regulatory inventory, covering EU regulatory frameworks that are applicable to nanomaterials (chemicals, worker protection, environmental legislation, product specific legislation etc.). The purpose of this inventory is to "examine and, where appropriate, propose adaptations of EU regulations in relevant sectors" as expressed in Action 6d) of the Commission Action Plan. Preliminary findings indicate that the regulatory frameworks in principle give a good coverage; different aspects of production and products are at the same time subject to various Community provisions. Implementation is facilitated by different types of documents, adopted within this regulatory framework, such as implementing legislation, European standards, regulatory and technical guidance documents that may have to be adapted in order to cover HSE risks in relation to nanomaterials. However, many of the knowledge gaps (toxicity thresholds, test schemes etc) will need to be addressed to ensure implementation and adaptation of ‘supporting documents’. Those knowledge gaps are in line with the ones earlier identified by EC and others and reported to the OECD. The Commission’s report therefore will also indicate initiatives undertaken (e.g. Research Framework Programmes, activities of Joint 10 OECD; 3rd Meeting of the Working Party on of Manufactured Nanomaterials, 28-30 November 2007, Current developments in delegations on the safety of manufactured nanomaterials – Tour de Table

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Research Center, cooperation within OECD, standardisation, Scientific Committees) in order to improve knowledge levels, so as to allow a proper implementation of the EU regulatory framework.

In the chemicals regulatory area, EU competent authorities (CAs) have decided that:a. The decisive criterion whether a nanomaterial is a new or existing substances is the same as

for all other substances, i.e. whether or not the substance is on EINECS. When a nanomaterial is derived from an existing substance, article 7.1 of the Existing Substances Regulation 793/93 (ESR) on the updating of reported information applies.

b. Nanomaterials having specific properties may require a different classification and labelling compared to the bulk material, also when the nanoform is derived from a bulk substance.

c. They invite industry to provide a number of dossiers on different representative nanomaterials, to show what kind of data is available, how risk assessment is being performed and how the risks are controlled.

d. For the longer term, a review of the applicability of testing methods and risk assessment methods should be carried out. This should be done at international level (e.g. within the OECD chemicals programme) with active input from industry and contributions from the EU.

REACH (regulation (EC) No 1907/2006) was adopted on the 18 December 2006 and published in the Official Journal of the European Union on 30.12.2006. REACH will gradually revoke and replace several of the existing EU legislation on chemicals. REACH entered into force on 1st June 2007. The European Chemical Agency ECHA in charge of following-up the registration, the evaluation and the authorisation process under REACH, was opened on the same day in Helsinki. Nanomaterials are covered by the provisions of this Regulation.

2. Developments related to voluntary or stewardship schemes

The EC has not developed any voluntary or stewardship schemes at this stage. Issues regarding information on nanomaterials will be discussed in the chemicals CAs working group, also as a follow-up to 1.c. above.

3. Information on any risk assessment decisions

In relation to nanomaterials in chemicals legislation, risk assessment and management is implemented at this moment as for other chemicals in the framework of the current legislation on new and existing chemicals (see 1.a. above). More specific guidance and information may be required in the future.

The EU Scientific Committee on Emerging and Newly Identified health Risks (SCENHIR) has produced two Opinions in relation to nanomaterials risk assessment, respectively on 10 March 2006, and on 21-22 March 2007. In its first opinion, SCENHIR concluded that the existing toxicological and ecotoxicological methods are appropriate to assess many of the hazards associated with the products and processes involving nanoparticles, but that they may not be sufficient to address all the hazards. Therefore the risk assessment needs to be done on a case-by-case basis. The assays may need to be supplemented by additional tests, or replaced by modified tests, as it cannot be assumed that current scientific knowledge has elucidated all the potential

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adverse effects of nanoparticles. Specifically, attention needs to be given to the mode of delivery of the nanoparticles to the test system to ensure that it reflects the relevant exposure scenarios.

For exposure, SCENIHR also expressed that the use of mass concentration data alone to express dose is insufficient, and the number concentration and/or surface area would need to be used as well. Equipment that enables routine measurements for exposure to free nanoparticles is not yet available. In particular, existing methods used for environmental exposure assessment may not necessarily be appropriate for determining the environmental fate of nanomaterials. Consequently, current risk assessment procedures may require modification for nanoparticles both regarding test methods for hazard identification and exposure assessment.

The SCENHIR suggested that 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 humans and ecosystems to be performed.

In its second opinion, dealing particularly with the appropriateness of the risk assessment methodology in accordance with the Technical Guidance Documents (“TGD”) for new and existing (chemical) substances for assessing the risks of nanomaterials, the SCENHIR concluded that current methodologies described in the TGDs are likely to identify certain hazards, but modifications are required for the assessment of risks to human health and the environment.. Furthermore, the opinion highlights needs to determine appropriateness of current test procedures for the prediction of human health hazards and estimation of risks for all types of nanoparticles. In particular, the SCENIHR focussed on the potential of nanomaterials to reach new target organs in the body, when administered in similar ways than bulk chemicals (translocation). This observation would lead to additional requirements of test methods to demonstrate potential new hazards.

On 19 June 2007, the Scientific Committee for Consumer Products (SCCP) adopted an Opinion for public consultation in June 2007 on safety of nanomaterials in cosmetic products. For labile particles, conventional risk assessment methodologies based on mass metrics may be adequate, whereas for the insoluble and slowly soluble particles other metrics, such as the number of particles, and their surface area as well as their distribution are also required. It is crucial when assessing possible risks associated with nanoparticles to consider their uptake. It is primarily for the insoluble and slowly soluble particles that health concerns related to possible uptake arise. Should they become systemically available, translocation/ transportation and eventual accumulation in secondary target organs may occur. The Committee also identifies a number of knowledge gaps. More particularly as regards the ban on animal testing with respect to cosmetics, the Committee takes note that at present no methodology has been validated for nanomaterials. Finally, the Committee states that review of the safety of the nanomaterials presently used in cosmetics is required.

4. Information on any developments related to good practice documents

The Commission is closely following the work in ISO and CEN. Both nanotechnology related Technical Committees in ISO (TC 229) and in CEN (TC 352) are currently working on the nomenclature and hence on the definition aspects. In ISO/TC 229, the working group on Health, Safety and Environment is proposing a Technical Report on "Current Safe Practices in Occupational Settings Relevant to Nanotechnologies". In addition, in ISO/TC 146 on Air Quality,

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the SC2 subcommittee on Workplace atmospheres has released a technical report ISO/TR 27628:2007 "Ultrafine nanoparticles and nano-structured aerosols – Inhalation exposure characterization and assessment". In ISO/TC 24/SC4 (Sizing by methods other than sieving), the particular issue of nanoparticle size measurements and the required reference materials is considered with more care

5. Research programmes or strategies designed to address human health and/ or environmental safety aspects of nanomaterials

As stated in Action Plan on Nanosciences and Nanotechnologies (N&N), the European Commission aims at reinforcing N&N research and development in the seventh framework programme for research, technological development and demonstration activities (FP7) and has proposed a significant increase of the budget compared to FP6.

It has also committed itself to boost support for collaborative R&D into the potential impact of N&N on human health and the environment via toxicological and ecotoxicological studies as well as developing appropriate methodologies and instrumentation for monitoring and minimising exposure in the workplace.

Activities in FP7 have been started: In the first call for proposals, several topics were launched specifically addressing the safety of nanomaterials. The proposals received in these topics have all now been evaluated and the research projects will begin by the start of 2008 (except for one that has already started).

NMP-2007-1.3- 1(Large scale integrating projects)

Specific, easy-to-use portable devices for measurement and analysis

NMP-2007-1.3- 2(Small or medium-scale focused research projects)

Impact of engineered nanoparticles on health and environment

NMP-2007-1.3- 3(Coordination and support actions)

Critical review on the data and studies on the potential impact on environment and health of nanoparticles

NMP-2007-1.3- 4(Coordination and support actions - only one database and support action will be funded)

Creation of a critical and commented database on the impact of nanoparticles

NMP-2007-1.3- 5(Coordination and support actions)

Coordination in studying the environmental and health impact of nanoparticles and nanotechnology based materials and products

HEALTH-2007-1.3- 4(Small or medium-scale focused research projects) Call coordinated with NMP-2007-4.1.3-2/4.4-4

Alternative testing strategies for the assessment of the toxicological profile of nanoparticles used in medical diagnostics

Dedicated calls are foreseen among the next actions of the FP7.

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The JRC is developing a research activity in collaboration with EU partners on risk assessment of engineered nanomaterials. The activities in FP7 focus on the development and harmonization of methods for toxicity testing of nanomaterials, the in vitro test of a representative set of MN on critical cell lines and encompass related studies on nanometrology and reference materials as well as the development of databases and studies on the applicability of 'in silico' methods adapting the traditional QSAR paradigm.

The Commission is considering supporting the development of a database containing substance information specific to nanomaterials. IUCLID could serve as a basis and could be further developed and adapted to the requirements related to nanomaterials datasets.

6. Information on any public/ stakeholder consultation

On 18 July 2007, the European Commission announced a public consultation on a Recommendation on a Code of Conduct for Responsible Nanosciences and Nanotechnologies Research. The consultation, that was open until 21 September, will provide input for a Recommendation on governance of this emerging area of science, which the Commission will put forward later this year. Contributions were received from a broad cross-section of European society, including the scientific community, industry, civil society, policy-makers, media and the general public.

The European Commission also open a Open Consultation on the Strategy on communication outreach in nanotechnology; The public and other stakeholders were invited to comment on the report and results from a workshop held by the European Commission it Brussels, February 6th 2007. This paper shaped operative recommendations for future European funding on appropriate communication and innovative approaches to engage the European civil society into a dialogue on nanotechnology. Experts in the field of science communication share success, best practices and challenge stories, to give to different audiences a "voice" in the policy making process. As a result, a set of recommended activities for Europe were outlined, which could be commented

The opinions from EU Scientific Committees, SCENIHR and SCCP are always submitted to public consultations before final adoption.

Several conferences on nanotechnology have been organised by different organisations throughout the EU and by recent EU Presidencies. The Finnish Presidency of the EU organized a conference on “Nanotechnologies: Safety for Success” in September 2006. In October 2007 the European Commission organised the another stakeholder dialogue related to consumer products.

7. Additional Information

The European Group on Ethics in Science and New Technologies (EGE) is a high-level group of independent experts on ethics appointed by President Barroso. The EGE advises the Commission on ethical issues related to science and technology or other relevant EU policies. The Group adopted an Opinion on ethical aspects of Nanomedicine in January 2007 (http://ec.europa.eu/european_group_ethics/index_en.htm).

Several research projects funded by the European Commission are related to innovation, ethical aspects and societal implications of nanotechnology. Additional information can be found at http://cordis.europa.eu/nanotechnology/. Linked to the European Technology Platform on Sustainable Chemistry, several documents are becoming available such as a code of conduct on

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nanotechnology; a guide on safe manufacturing and for activities involving nanoparticles at workplaces; and detailed information on the characterisation of nanomaterials. Moreover, the recent Nanosafety Hub event organised by the European Technology Platform on Industrial Safety (ETPIS) on the 23rd March 2007 in Brussels, BE provided an overview of progress on the development of detection and monitoring technologies and the state-of-the-art in the fields of toxicity of nanoparticles, secured integrated processes as well as workplace health, safety and environmental safety all linked to nanomaterials (more information are available on http://www.industrialsafety-tp.org/ & http://euvri.risk-technologies.com/events/event_3/default.htm).

A standardization mandate is currently in consultation with Member States to formally convey priorities to the European standards bodies and to request feedback on their activities. The European standards bodies are invited to forward a program of activities to the European Commission and Member States that subsequently can be endorsed by Commission and national authorities. The mandate states that European standardisation efforts will preferably be elaborated in cooperation with the international standards bodies.

Germany

The German Federal Environment Ministry launched the NanoDialogue project last year on behalf of the Federal Government. The aim is to provide support through the NanoCommission, to the sustainable development and use of nanomaterials. The NanoCommission is made up of academics, industry representatives, environmental and consumer associations, employees' representatives, federal representatives and the Länder. The NanoCommission has set itself three tasks. For these tasks, special working groups were installed:

1. The 1st working group concentrates on the question: How can using nanomaterials contribute to sustainable economic and social development in Germany, in particular as regards environmental/health and consumer protection? For instance, nanomaterials are already being used to improve photovoltaics installations; they also promise to make improvements to energy storage equipment and batteries.

The "Opportunities for the Environment and Health" Working Group wants to identify and describe select nano-enabled products or applications from which we can derive a special benefit for the environment, for consumers and as regards health protection. Because in some areas nanomaterials are still at an early stage of development, future potentials also need to be identified for this sector in Germany.

2. Where do we need to do risk and safety research to clarify the possible impacts on the environment and health from using nanomaterials? A second working group is called "Risks and Safety Research" and consequently deals with the possible risks posed by nanomaterials, especially the gaps in our knowledge, which we need to fill as soon as possible.

The aim is to work out a joint programme for future safety research plus suggestions for concrete projects. Since many products with nanomaterials are already on the market and we expect a further increase in the future, this working group wants also to give first recommendations regarding risk assessment for nanomaterials.

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One key difficulty in assessing the possible risks posed by nanomaterials is that in some cases new test and evaluation methods need to be developed. These include suitable means for measuring nanoparticles in environmental media and on/in the human body, as well as developing appropriate measuring and assessment strategies.

3. In order to provide preventive protection to employees, consumers and the environment, a third group is working on "Guidelines on the Responsible Use of nanomaterials". The group started the work on existing Guidelines for employment protection and is now working on basic principles on which Guidelines should be based and on indicators, for checking their implementation.

Possibly the result will be recommendations for dealing with lack of knowledge, possible “no-go areas” for release of nanomaterials into the environment or for potential damages for humans will be identified. But “No-go areas” could otherwise mean that there are also some kind of “innovation-spaces”, where the experts see few risks and where the advantages preponderate. The aim of working group 3 is that Industry and user Companies adopt this Guidelines as a “Code of Good Practice”.

The NanoCommission is very interested in initiatives of the OECD, the EU and other states in this area and wants to incorporate this into its work. In addition different Government/Industry funded projects are ongoing where nanomaterials are tested like Nanocare, Inos and Tracer and some Government or industry funded work in this area. This is embeded in activities of the EU.

Korea

The Korean government well recognized the importance of potential risks of nanomaterials, and is conducting several projects on human health and environmental safety of nanomaterials. Ministry of Environment (MOE) implemented a new project on the safety of manufactured nanomaterials in the framework of Ecotechnopia 21 project which has been conducted to promote the development of environmental technologies since 2001. Ministry of Science & Technology (MOST) has performed a research project named environmental implications assessment of nanomaterials from 2006. Ministry of Commerce, Industry and Energy (MOCIE) has conducted research designated in ISO/ TC 229. Korea Food & Drug Administration (KFDA) has carried out a series of research projects on the toxicity of nanomaterials from 2007 to 2015 with the aim of the development of a toxicological assessment of nanomaterials and guidelines for the areas such as food, drug, medical product and cosmetics. In order to harmonize the policy on the safety of nanomaterials in Korea, MOE, MOST, KFDA and MOCIE established an inter-ministerial consultation body on the safety of nanomaterials in March 2007. The consultation body will play an important role to perform effective research and to develop harmonious policy in the nanosafety.

Issues covered by MOE, MOST, MOCIE and KFDA- to characterise nanomaterials- to establish test guidelines for the areas such as food, drug, medical product, and cosmetics.- (eco) toxicological assessment of nanomaterials - environment exposure and fate of nanomaterials - risk management of nanomaterials- survey the domestic and overseas trends on nanomaterial hazards

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Nigeria

In Nigeria, just like in many developing countries, the challenges and prospects of nanotechnology are still a very grey area with very limited ongoing national activities and little information on any existing activities. It is expected that the Forum session will provide an avenue for Nigeria and other developing nations to obtain information on the import and relevance of nanomaterials and for accessing available opportunities for capacity development in nanotechnology at the national and regional levels.

Some of the key areas of interest and challenges will be to: raise awareness on the subject matter, justify the relevance and import of nanotechnology to developing economies, identify any ongoing activities and expertise in this area, identify key stakeholders for capacity development, develop programmes of action for public and private sector buy-in with the main considerations for accruing benefits to the environment and human health.

Slovenia

Slovenia launched the first activities in the field of nanosafety in 2004 with participation in EU Accompanying Measure (GROWTH PROGRAMME): NANOSAFE - Risk Assessment in Production and Use of Nanoparticles with Development of Preventive Measures and Practice Codes) and its continuation as Integrated project: NANOSAFE 2 - Safe production and use of nanomaterials (2005-2009) and Co-ordination action IMPART - Improving the understanding of the impact of nanoparticles on human health and the environment (2005-2008). A partner in all these EU projects is Jozef Stefan Institute (www.ijs.si ).

On 4th and 5th September 2006 National Chemicals Bureau organized the International Conference on Chemical Safety and Safety of Nanomaterials. The conference was the final step of an intensive project Phare Twinning “Chemical Safety II”, No. SI 03 IB EC 02, which had been supported by the European Commission. The main twinning partners Slovenia and Austria with about 60 short term experts from 10 EU Member States had worked together with numerous experts from the Slovene working groups in different intersectoral priority areas of chemical safety. After the conference work went further and the book "Slovenia is made for nanotechnology" was published. Transition Facility Twinning "Advanced Chemical Safety - Third Stage Project" (in short “Chemical safety 3”), No. SI 06 IB EC 02, which started on 4th June 2007, expects that a brochure on safety of Nanomaterials in Slovene language might be prepared and published, that national strategy for nanomaterials is prepared, and that safety and that overall awareness on risks posed by nanomaterials is raised.The first national workshop on toxicity of nanoparticles organized by University in Ljubljana, Faculty for biotechnology, Jozef Stefan Institute, National institute for chemistry, and National institute for biology, was held on January 30, 2007 in Ljubljana. We have established a network of all researchers focused on the interaction of nanoparticles with living cells. The report was published as an article on literature survey in the topic including our research results in national journal Delo with 65.000 subscribers.

Public lectures about toxicity of nanoparticles and basic recommendations for their safe production and use have been given at two basic research institutions (Jozef Stefan Institute - Febr. 2007, National Institute for Chemistry – March 2007), where nanotechnology studies already started and at the Chamber of Craft of Slovenia – February 2007, with emphasis on nanoparticles released in industry as a side product or pollution. Résumé of the lecture was published in national journal Delo with 65.000 subscribers and in journal Obrtnik (specialized

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journal for Chamber of Craft) with 53.000 subscribers. Basic information on concerns relating to health risks of nanoparticles was published also on the website www.energetika.net, April 30, 2007 and released by national radio station RTV Slovenia, February 1, 2007.

In 2006/2007 we created a technological platform I-TECHMED: Innovative and Supportive Technologies for Medicine (http://www.itechmed.net/eng/index.aspx?menu=ep ).

The goal of the platform with 50 involved public and private organizations is to establish an efficient public-private partnership and to unite key stakeholders, who have a joint vision of technological development for a particular sector, under the leadership of industry. In the work group titled: Nanotechnologies for medical applications, the partners are decided to balance the positive and negative impacts of nanoparticles on health considering ethics risks coupled with enhanced chemical activity with decreasing the size of nanoparticles used as drug deliveries. Nanoparticles in medicine are either engineered if they are prepared for specific purpose, as example in drugs or creams, or they can be a side product of friction, as implant debris.

The first course of nanotoxicology at University in Ljubljana with the expected students in school year 2008-2009 is currently in the preparation stage.

Jozef Stefan Institute is proposing the following actions to be taken on national level:

The action plan of Slovenia covers the following issues:- To register all producers of mass quantities of engineered nanoparticles synthesizing for the

market- To establish a national network on safe production and use of nanoparticles- To prepare recommendations for producers and users of nanoparticles- To recommend the size-distribution measurements of NPs at work place and in environment- To prepare the monitoring strategies at the production plants (personal sampling is preferred

to ensure an accurate representation of the worker’s exposure).

Switzerland

In Spring 2006 work on the Swiss Action Plan was officially launched. A work package is developed in collaboration with experts and stakeholders in order to identify critical applications of manufactured nanomaterials and to minimize possible detrimental effects on human health and the environment. The coordination of this work package with international organizations (OECD, ISO) and EU is important. The promotion of safety research on manufactured Nanomaterials and the dialog with the public and stakeholders are other objectives of the Action Plan. The first deliverable of the action plan was a basic report, published in July 2007 (http://www.umwelt-schweiz.ch/nanotechnologie), containing an overview of the current knowledge about the risks of manufactured nanoparticles. Topics discussed are human toxicity and ecotoxicity of nanomaterials, occupational health and safety, regulation and standardisation, the assessment of the consequences of technology and communication. Finally, a list of risk research needs is presented.

Present Swiss legislation does not take the specific properties of manufactured nanomaterials into account. The action plan of Switzerland covers the following issues: - Product information for consumers- Guidance for self-supervision- Information about manufactured nanomaterials on the material safety data sheets

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- Maximum tolerable concentrations at the workplace- Regulation of waste disposal- Obligations to report, notify or authorisation (test requirements, special procedures for the

registration of nanoparticles)- Limitation of emissions into the environment- Regulation on major accidents (tonnage thresholds)

Thailand11

In 2003 the Royal Thai Government established the National Nanotechnology Center (NANOTEC) under the umbrella of the National Science and Technology Development Agency (NSTDA), a non-government public institution. NANOTEC has a mandate to formulate a National Nanotechnology Strategic Plan (2004 - 2013) for Thailand as well as to establish nanotechnology operational plans and the guidelines. NANOTEC's main objectives are: to conduct and promote nanotechnology research in order to improve the competitiveness of Thai industries, to develop well trained human resources in the field of nanotechnology, to establish networks and collaborations with other research centers, academics, industrial sectors national and internationally, and to promote public awareness and understanding of nanotechnology. NANOTEC with the collaboration of the Office of the Consumer Protection Board is developing a nano-label (or nanomark) to verify properties and improvement on a nanoproduct. NANOTEC as a funding agency has urged researchers to add the safety aspects to all nanomaterial R&D grant proposals. Safety data should be available through NANOTEC after the research works are completed. Nevertheless, there has never been a research program specifically designed to address human health and/ or environmental safety aspects of nanomaterials as such.

A national policy body to handle nanosafety issues has been established and called for the drafting of a nanosafety and nanoethics guideline. NANOTEC has engaged Chulalongkorn University to prepare the nano-safety and nano-ethics guideline that will covered nanotechnology research, development, manufacturing, transport, usage, consumption, and the treatment/ disposal of wastes arising from any of the mentioned activities. The project was divided into 3 phrases with the first one starting in April 2007. The main objective of the first phase is to gather international information on all aspects of nanosafety and nanoethics. Phase 1 aims to familiarize experts in various fields with nanotechnology. These experts from the fields of environmental law, consumer protection law, economics, and political science, are expected to contribute to the second and third phases of the project, where local status and trends will be assessed and the nanosafety/ nanoethics guidelines will be drafted, respectively.

Chulalongkorn University has formed a forum of nanosafety with the objective of sharing information among interested faculty members & researchers. In addition, a public hearing in nanosafety and toxicity in nanomaterials was held in October 2007. The participants were composed of researchers, public and government sector.

11 Information taken from: OECD; 3rd Meeting of the Working Party on of Manufactured Nanomaterials, 28-30 November 2007, Current developments in delegations on the safety of manufactured nanomaterials – Tour de Table

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United Kingdom

The UK aims to promote the responsible development, use and fate of nanomaterials while protecting people’s health and safety and protecting the environment. A key objective is managing any potential risks to the environment and human health via the environment. Implementation of Government activities on nanotechnologies is co-ordinated through the Nanotechnology Issues Dialogue Group (NIDG) made up of Government departments, agencies and the devolved administrations. Progress and delivery was independently reviewed after two years and will be reviewed again after five years.

There is currently little evidence on which to determine the potential risks posed by engineered nanoscale materials. It is therefore difficult to assess the extent to which current controls and regulations cover these materials, or the type of additional measures that may be necessary to control potential risks. To address this, the UK has developed a comprehensive programme of research on potential risks and a Voluntary Reporting Scheme for engineered nanoscale materials.

The UK Government funded around £10 million of Environment, Health and Safety related research between 2005 and 2008. This sat alongside major funding for research into the fundamental science behind the nanotechnologies through the UK Research Councils, which provide the bedrock on which nanotechnology research is growing in the UK. The UK has identified 19 Environmental, Health and Safety research objectives and developed action plans to meet them. A second Government research report which places UK activities into an international context was published in November 2007.

The UK Voluntary Reporting Scheme was established for industry and research organisations to provide information relevant to understanding the potential risks posed by free engineered nanoscale materials. The scheme is voluntary and will not replace existing legislation. It has run from September 2006 to September 2008.

All policy activities are informed by an ongoing programme of stakeholder involvement, centered around meetings of a Nanotechnologies Stakeholder Forum. This group is made up of key stakeholders from industry, civil society groups and academia. Stakeholder involvement is complemented by work to ensure wider public dialogue on the role and management of nanotechnologies in society. As part of this, a Nanotechnology Engagement Group was funded to draw together and reflect on a variety of public engagement projects, and then feed key conclusions back to Government.

The UK recognises that the challenges posed in ensuring the responsible development of nanotechnologies is too great to be solved by any one country alone. This is why we have been working with international partners, in particular, the European Commission and the OECD to share efforts and avoid duplication.

Further details may be found at: www.defra.gov.uk/environment/nanotech/index.htm

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9 Annex

9.1 Definitions and types of manufactured nanomaterials

The definition of nanotechnology should be capable of identifying nanomaterials, nano-intermediates and all nano-enabled products where they are purposefully engineered to achieve size-dependent properties and functions. A definition should exclude accidental, natural, and incidental nanomaterials. Currently, several organizations have proposed and published definitions and descriptions.

Definitions of Nanotechnology12

"There are currently dozens of different definitions of what nanotechnology is or could be; and it is important to realize that none has been agreed upon. Definitions are also political and ethical – they can determine what people will pay attention to, worry about, ignore or investigate. The fact that there are many definitions is a good indication that nanotechnology (like other emerging sciences such as biotechnology) will likely confuse the settled categories of pure and applied research, and of publicly and privately funded research. Different disciplinary backgrounds and different national scientific establishments will bring different concerns and ideas to bear on what nanotechnology will become."

The UNESCO publication describes at least five definitions in use and notes that "Different groups define nanotechnology differently, depending on what they hope it will achieve …..These definitions also vary according to the interests of nations and social actors interestedin nanotechnology…"

In a the review carried out for ECETOC the following definitions and descriptions of the different types of manufactured nanomaterials, nano-tools and nano-devices are mentioned13:

Nanoscience is the study of phenomena and manipulation of materials at atomic, molecular and macromolular scales, where the properties differ significantly from those at a larger scale;

Nanotechnologies are the design, characterisation, production and application of structures, devices and systems by controlling shape and size at nanometre scale 14.

Nanotechnology: the manipulation, precision placement, measurement, modelling or manufacture of sub-100 nanometre scale matter 15.

12 The Ethics and Politics of Nanotechnology (UNESCO, 2006) http://unesdoc.unesco.org/images/0014/001459/145951e.pdf

13 Borm PJA, Robbins D, Haubold S, Kuhlbusch T, Fissan H, Donaldson K, Schins R, Stone V, Kreyling W, Lademann J, Krutmann J, Warheit D, Oberdörster E: The potential risks of nanomaterials: a review carried out for ECETOC. Part Fibre Toxicol. 2006, 3:1-35.

14 The Royal Society and the Royal Academy of Engineering: Nanoscience and nanotechnologies: opportunities and uncertainties; 2004.

15 Meyer M, Kuusi O: Nanotechnology: Generalizations in an Interdisciplinary Field of Science and Technology (2002), Vol., No.2 (2004), pp. International Journal for Philosophy of Chemistry; 2002, 10: 153-168.

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Nanotechnology is dealing with functional systems based on the use of sub-units with specific size dependent properties of the individual sub-units or of a system of those 16.

Nanomaterials, nanotools and nanodevices

Nanomaterials:Materials with one or more components that have at least one dimension in the range of 1 to 100 nm and include nanoparticles, nanofibres and nanotubes, composite materials and nano-structured surfaces. These include nanoparticles as a subset of nanomaterials currently defined by consensus as single particles with a diameter < 100 nm. Agglomerates of nanoparticles can be larger than 100 nm in diameter but will be included in the discussion since they may break down on weak mechanical forces or in solvents. Nanofibres are a sub-class of nanoparticles (include nanotubes) which have two dimensions <100nm but the third (axial) dimension can be much larger.

Nanotools:Tools and techniques for synthesising nanomaterials, manipulating atoms and fabricating device structures, and - very importantly - for measuring and characterising materials and devices at the nanoscale.

Nanodevices:Devices at the nanoscale, important in microelectronics and optoelectronics at the present time, and at the interface with biotechnology where the aim is to mimic the action of biological systems such as cellular motors. This latter area is the most futuristic, and excites the greatest public reaction.

9.2 Health risks

In addition to the dose and the elemental composition of the nanoparticles, factors such as their surface area, the function of the surface, tendency to aggregate, the form of the particles and their surface charge all play decisive roles in their distribution through the body, and their possible (genetic) toxicity. In aqueous systems, the solution pH and the presence of adsorbing molecules and ions affect their surface charge and, hence, strongly influence aggregation behavior. The rate of dissolution is proportional to particle surface area, and consequently nanoparticulate materials should dissolve faster than larger-sized bulk materials. Nanoparticle toxicity is strongly coupled with chemical toxicity of particular elements composing a nanoparticle. Quantum size effects through changes in electron level distribution and ionization energy of the smallest nanoparticles influence the electro-magnetic interaction with a cell organelles as well.

For most nanoparticles it is not clear whether and how they are taken up in the body, distributed, metabolised, accumulated and secreted. Kinetic models can help in the estimation of realistic doses of particles in target organs that could be affected. Thus, the question can be resolved of which exposure paths are relevant for various nanoparticles and whether certain target organs can be excluded (for the moment), when setting the first priorities. In addition to particles themselves,

16 Schmidt G, Decker M, Ernst H, Fuchs H, Grunwald W, Grunwald A et al. Small dimensions and material properties. Europaische Akademie Graue Reihe. A definiton of nanotechnology; 134; 2003. Bad Neuenahr.

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the potential health and ecological impacts of their breakdown products (metabolites in biological systems, and degradates in ecosystems) also have to be considered.

The lungs are the primary target site for inhaled nanoparticles, although there is also evidence of some inhaled nanoparticles being transported from the nasal passages into the brain (discussed below). Lungs have an enormous exposed area, and inhaled and deposited nanoparticles can get into the bloodstream through the extremely thin air-blood-tissue barrier. From the bloodstream, some nanoparticles have been shown to penetrate lipid bi-membranes and get into organelles such as mitochondria and nuclei, which can cause oxidative stress or damage to DNA. Many studies using animals or cell cultures have reported oxidative stress and inflammatory responses following nanoparticles exposure. In addition to the lungs, the skin provides a potential uptake surface following dermal exposures (such as for cosmetics, sunscreens, and nanoparticle-impregnated clothing). Studies have demonstrated that the intact skin protects the body efficiently and effectively against nanoparticles (TiO2 in sunscreens). However very specifically engineered particles might penetrate, and a generic conclusion regarding skin penetration does not exist. Access from the dermis to lymphatic and blood circulation is considered possible or likely. Penetration into the skin especially in the case of inflammatory or traumatic lesions is very likely as it was even demonstrated for larger particles.

Oral ingestion of nanomaterials has not been adequately tested to date. Once ingested, some scientific studies report that nanoparticles are excreted efficiently through the intestine for small particles (< 100 nm) increased uptake through the intestinal wall has been observed in rats.

A number of studies have demonstrated that some nanomaterials are efficiently transported directly from olfactory neurons into the central nervous system, crossing the blood-brain barrier. Data on translocation between organs are based on different approaches, so they cannot yet be considered to have been confirmed. According to various studies surface-modified nanoparticles crossed the blood-brain barrier. It has not yet been reported in the public literature whether the blood-testis barrier or the placental barrier can also be crossed, but it is suspected that these things are possible, in view of the fact that the particles are in the range of nm.

9.3 Occupational health

At the workplace, according to our present knowledge, exposure to nanoparticles occurs primarily through handling nanoparticles that were produced for a specific purpose, and through working practices that generate nanoparticles as unintended by-products. Although there is not yet an overview of the types, quantities, or forms of application of nanoparticles, as by-products they are considered to be the most widespread source of exposure in the workplace (aka: ultra-fine particles).

There have not yet been any epidemiological studies on the health risks of modern manufactured nanomaterials. Concentrations at the workplace have begun to be measured, and it is not clear whether the current models for local and temporal concentration profiles apply in the case of new nanomaterials. At present apart from a convention between a few European institutes of occupational safety there are no international standards on methods for measuring nanoparticles and for estimating exposure to them. ISO has created a committee on nanotechnology17, in order to produce norms based on scientific knowledge in the areas of health, safety and the

17 ISO Technical Committee (TC) 229 «Nanotechnologies».

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environment. Until norms in this area become available, exchanges of experience between measuring engineers and scientists will be particularly important.

The known strategies to reduce exposure in the workplace also apply to dealing with nanomaterials. Appropriate protection measures are evaluated and defined by specialists in occupational health and safety as part of an assessment of risks throughout the company. In some countries the principle applies that new substances with unknown properties should be treated as potentially dangerous. Organisational protection measures should primarily be taken, supported by technical protection measures and the substitution of preparations that form powders.

Personal protection equipment can occasionally supplement these measures, but it should not replace them. Current recommendations are firmly based on analogy with handling larger particles. A number of studies exist showing that correct use of technical protection systems and personal protection equipment is effective18.

Until more is known, there is still a lack of the scientific informationand methodological basis to carry out a robust risk assessment of nanomaterials. Several large-scale programmes are running or being planned in various countries and at the international level. These will deal with different aspects of risk research on nanomaterials. In this context, it is critical to have a coordinated, strategic approach to deal with the most important issues.

9.4 Environmental risks

At present, only a few studies have been carried out on the ecotoxicity and environmental behaviour (fate and transport) of nanomaterials. So far, numerous studies have reported on the highly toxic impacts of nanomaterials on aquatic organisms, however many of these studies are limited because the test material was inadequately characterized , and some findings have been challenged.

There are not yet any reliable estimates of possible environmental inputs that could occur during the production, use and disposal of nanomaterials or products containing nanomaterials. In particular there is a lack of suitable methods to measure nanomaterials in the environment. Similarly, scarcely any studies have been carried out on by-products and breakdown products of nanomaterials. The basic aspects of the behaviour of micrometre-range particles in the air or in aqueous solutions have been clearly described and they can be understood in terms of quantitative models. As far as possible, nanoparticles should be introduced into these existing models, or appropriate new models should be developed. Normally, nanoparticles in gases can be removed relatively simply by rapid agglomeration to bigger structures by diffusion filtration or depth filtration. In liquids this may be difficult under certain circumstances if there are stabilized dispersions. The effectiveness of breakdown in wastewater treatment works has barely been examined so far. Preliminary investigations show that the present treatment process may not be sufficient, but the literature is not all in agreement. So far, there are few studies exploring bioaccumulation and the possibility of the accumulation of nanoparticles in the food-chain. However, investigations show that nanoparticles can be taken up by organisms in the environment. We have to consider on one hand the storage of lipophilic nanoparticles in fatty tissues, and the resultant concentration in the food-chain, and on the other hand the accumulation

18 See studies presented at http://nano-taiwan.sinica.edu.tw/2007_EHS2007/index.htm and the NIOSH June 2007 Report http://www.cdc.gov/niosh/docs/2007-123/pdfs/2007-123.pdf

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of persistent nanoparticles in ecosystems and organisms if there are no pathways for their breakdown or excretion.

The specific physical and chemical properties of nanoparticles compared with larger particles can present unexpected safety risks. The most important physico-chemical dangers are the risks of fire or explosion and of unexpectedly increased catalytic activity. So far, these dangers have been classified as relatively low for many manufactured nanomaterials, as nanoparticles are produced in relatively small quantities. However, this is likely to change rapidly in the future.

In clouds of dust, the size of the particles and the related specific surface area are critical for the explosion characteristics. Basically, the smaller the particles are, the greater the risk of a dust explosion will be. However, the physico-chemical properties of many particles are still only partly understood, so it is difficult to estimate these risks.

9.5 Ethical issues

A 2006 UNESCO publication19 states "... ethical issues in relation to nanotechnology should be identified and analyzed so that the general public, specialized groups and decision-makers can be made aware of the implications of the new technology. Since nanotechnology is developing quickly, an anticipatory approach to ethical issues is necessary." … "From the perspective of UNESCO, even if nations are not actively pursuing research in nanotechnology, they should nonetheless have a stake in defining the proposed outcomes and actual course of research according to norms of equity, justice and fairness. ……. At this early stage, citizens of every nation have a stake in understanding what nanotechnology is becoming and could be."

The UNESCO publication presents a number of ethical issues that the international community will face in the near future. The report states that as the use of nanomaterials and nanoscale production processes is commercialized new ethical and political issues can be generated and old ones will be activated. It further states that "nanotechnologists are hyper-aware of the need to study both potential uses and potential harms well in advance of their commercialization. This recognition and precautionary direction to corporate research is novel." It notes that the institutional and organizational framework for address the concerns across competing interests associated with creating and adoptions of standards and international best practices are not yet well developed.

The report states that the ease of communication and access to information by experts in most countries would indicate that nanotechnology will be an international scientific project and the "knowledge divide" between countries may look different from the past with the possibility of the greatest divide within nations rather than between nations. Relevant to this is the question of how nanotechnology research that could benefit the poorest should be promoted, for example research on applications that could address the Millennium Development Goals.

A related question is the extent to which all nations will benefit equally from the new scientific knowledge – on nanotechnology and innovative research more generally. The report notes the issues of intellectual property rights and rewards, public scrutiny of scientific research, accountability of research and the use of scientific information in the context of antiterrorism 19 The Ethics and Politics of Nanotechnology (UNESCO, 2006) http://unesdoc.unesco.org/images/0014/001459/145951e.pdf

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efforts all may impact the kind and quality of science. The lack of the necessary infrastructure to manage good science may result in developing countries unable to obtain the best and most reliable scientific knowledge and practices.

Manufactured nanomaterials and the precautionary approach:

Even though there are uncertainties and gaps in our knowledge of possible adverse impacts of manufactured nanomaterials (cf. 8.2, 8.3, 8.4), we are not in a situation of complete ignorance. For initial toxicological tests indicate that at least some manufactured nanomaterials may cause serious harm to humans and the environment if inappropriately used through their lifecycle.

If this is an adequate description of the current state of knowledge the question arises of how we should assess the risks of manufactured nanomaterials from an ethical viewpoint and what we should do with regard to the regulation of these materials. Concerning this question one finds, roughly speaking, two opposing views in current literature:

1. There are those who argue that, although some indications of the potential risks of some manufactured nanomaterials for humans and the environment can be recognized, we are used to using all kinds of potentially dangerous materials/products on a daily basis, and have learned how to manage the risks involved and benefit from these materials/products. In particular there is no factual reason to assume that these risks are of a kind that would justify the application of the strong precautionaryapproach, especially the reversal of burden of proof. That does not mean that the production and utilization of manufactured nanomaterials for commercial or scientific purposes does not require any kind of state regulation or an adaptation of existing regulatory frameworks to cover the specific properties of manufactured nanomaterials . For instance, asking producers of nanomaterials and nano-enabled products containing free manufactured nanoparticles to carefully analyse the risks associated with these particles or asking them to reduce the exposure in the workplace as much as possible may be perfectly warranted. (Risk research, i.e. research to reduce uncertainty, premarket testing, reduction of exposure etc. are all precautionary measures.) Nevertheless, manufactured nanomaterials may be used in scientific research as well as in commercial products even if there is some – as yet inconclusive – evidence that they may not be completely harmless.

2. There are those who claim that for the time being at least the use of free manufactured nanoparticles in commercial products and the deliberate release of those particles in the environment should be prohibited. In order to justify this they invoke the strong version of the precautionary approach. In particular they argue that the risks associated with these particles warrant a reversal of the burden of proof: rather than proof of risk by the State, a product must be proved harmless by its producer. This does not mean that proof of zero risk is required; it is enough to produce solid scientific evidence that the risks are able to be identified and managed/mitigated effectively,

The main theoretical question in this context is: Which conditions must be met for the adoption of precautionary measures? More specifically: What kind of empirical evidence regarding the risks of manufactured nanomaterials justifies what kind of precautionary measure? There seems to be agreement that some nanomaterials such as carbon nanotubes and buckyballs do have the potential to cause considerable harm in humans and the environment. But given the knowledge gained from in vitro- and in vivo research thus far what kind of regulatory measures are most

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suitable to manage exposure to hazard? At the moment this is hard to tell. The reason is that it depends on how one interprets the available and limited scientific data. How do we draw the line between reasonable precaution and excessive precaution?

Yet there is one point where there is unanimity: Because it is clear that at least some (free) manufactured nanomaterials are not harmless and because the occurrence of harm must be avoided as far as possible there is a moral obligation to press ahead with risk research.

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