A critical assessment of the European Commission's proposals for the risk assessment and registration of chemical substances in the European Union

In May, 2003, the European Commission published detailed proposals relating to its 2001 White Paper - Strategy for a Future Chemicals Policy. The White Paper described a new registration system called the REACH (Registration, Evaluation and Authorisation of Chemicals) system, for both new and existing chemicals. Subsequently, these detailed proposals were available for an eight-week consultation period for stakeholders to voice their views and concerns. In this paper, we describe our reactions to the Commission's more-detailed proposals. These include the creation of a European Chemicals Agency to implement the REACH system in conjunction with Competent Authorities (CAs) in Member States and the Commission itself. Unfortunately, many of our concerns and suggestions, previously voiced and shared with several other key stakeholders, remain unanswered, but are as relevant as when the White Paper was published. In particular, we are concerned about the lack of a clear and coherent strategy. There is no guidance for registrants on intelligent testing to maximise the use of non-animal approaches to safety testing, based on a combination of factors for estimating exposure levels, rather than mainly on production volumes. We are also concerned about the absence of a clear programme for the development, improvement and validation of new alternative methods, in conjunction with the Commission's own unit, the European Centre for the Validation of Alternative Methods, as well as other organisations with relevant expertise and experience, including FRAME. Finally, we explain why such measures should be introduced, together with clearer guidelines for the respective roles of the Agency, the CAs and the Commission in implementing and harmonising the REACH system at the European Union and Member State levels. A series of recommendations are made, to improve the situation and to improve the risk assessment process.     

A critical assessment of the European Commission's proposals for the risk assessment and registration of chemical substances in the European Union

In May, 2003, the European Commission published detailed proposals relating to its 2001 White Paper--Strategy for a Future Chemicals Policy. The White Paper described a new registration system called the REACH (Registration, Evaluation and Authorisation of Chemicals) system, for both new and existing chemicals. Subsequently, these detailed proposals were available for an eight-week consultation period for stakeholders to voice their views and concerns. In this paper, we describe our reactions to the Commissions more-detailed proposals. These include the creation of a European Chemicals Agency to implement the REACH system in conjunction with Competent Authorities (CAs) in Member States and the Commission itself. Unfortunately, many of our concerns and suggestions, previously voiced and shared with several other key stakeholders, remain unanswered, but are as relevant as when the White Paper was published. In particular, we are concerned about the lack of a clear and coherent strategy. There is no guidance for registrants on intelligent testing to maximise the use of non-animal approaches to safety testing, based on a combination of factors for estimating exposure levels, rather than mainly on production volumes. We are also concerned about the absence of a clear programme for the development, improvement and validation of new alternative methods, in conjunction with the Commissions own unit, the European Centre for the Validation of Alternative Methods, as well as other organisations with relevant expertise and experience, including FRAME. Finally, we explain why such measures should be introduced, together with clearer guidelines for the respective roles of the Agency, the CAs and the Commission in implementing and harmonising the REACH system at the European Union and Member State levels. A series of recommendations are made, to improve the situation and to improve the risk assessment process.     

The EC White Paper on a Strategy for a Future Chemicals Policy

The European Commission (EC) White Paper on a Strategy for a Future Chemicals Policy calls for the collection of adequate information about chemicals, in order to ensure their appropriate risk management. The White Paper proposes a stepwise and flexible approach to all chemicals produced in amounts above 1 tonne/year/manufacturer, including testing, if information cannot be provided by other means. The required information should be collected by the end of 2012. The EC services are currently preparing the drafts for the future chemicals legislation.     

A survey of stakeholder organisations on the proposed new European chemical policy

In February 2001, the European Commission published a White Paper proposing that a single new system of chemical regulation should be applied throughout the Member States of the European Union. The proposed Registration, Evaluation and Authorisation of Chemicals (REACH) system was to include both new and existing chemicals, with the aim of ensuring that sufficient pertinent data were made available to enable human health and the environment to be protected. The policy was founded on the principle of sustainable industrial development, and ambitiously attempted to incorporate the needs and views of key stakeholder organisations, such as industry, trade associations, consumer groups, environmentalists, animal welfarists and Member State governments. During the period between the publication of the White Paper and the on-line publication of consultation documents, as part of a public consultation exercise, in May 2003, many of these key stakeholder organisations produced material in support of or critical of the White Paper, either in part or as a whole. In this paper, we have attempted to review this extensive material and to present it in the context of the current chemical regulatory system that the REACH system will replace. Emphasis is placed on the impact of the new policy on the number of animals used in the testing regimes within the REACH system and the inclusion of alternative methods into the legislation. Although supportive of the overriding aims of the new policy, FRAME believes that the fundamental concept of a risk-free environment is flawed, and that the new REACH system will involve the unjustifiable use of millions of laboratory animals. The new policy does include alternative methods, particularly for base set substances. Nevertheless, alternative testing methods that are already available have been excluded and replaced with outdated in vivo versions. There is also insufficient detail with regard to the further development and validation of alternative methods, particularly for substances of high concern, such as endocrine disrupters or reproductive toxins, for which no alternative testing methods currently exist.     

A survey of stakeholder organisations on the proposed new European chemicals policy

In February 2001, the European Commission published a White Paper proposing that a single new system of chemical regulation should be applied throughout the Member States of the European Union. The proposed Registration, Evaluation and Authorisation of Chemicals (REACH) system was to include both new and existing chemicals, with the aim of ensuring that sufficient pertinent data were made available to enable human health and the environment to be protected. The policy was founded on the principle of sustainable industrial development, and ambitiously attempted to incorporate the needs and views of key stakeholder organisations, such as industry, trade associations, consumer groups, environmentalists, animal welfarists and Member State governments. During the period between the publication of the White Paper and the on-line publication of consultation documents, as part of a public consultation exercise, in May 2003, many of these key stakeholder organisations produced material in support of or critical of the White Paper, either in part or as a whole. In this paper, we have attempted to review this extensive material and to present it in the context of the current chemical regulatory system that the REACH system will replace. Emphasis is placed on the impact of the new policy on the number of animals used in the testing regimes within the REACH system and the inclusion of alternative methods into the legislation. Although supportive of the overriding aims of the new policy, FRAME believes that the fundamental concept of a risk-free environment is flawed, and that the new REACH system will involve the unjustifiable use of millions of laboratory animals. The new policy does include alternative methods, particularly for base-set substances. Nevertheless, alternative testing methods that are already available have been excluded and replaced with outdated in vivo versions. There is also insufficient detail with regard to the further development and validation of alternative methods, particularly for substances of high concern, such as endocrine disrupters or reproductive toxins, for which no alternative testing methods currently exist.     

Ethical, legal, and social aspects of farm animal cloning in the 6th Framework Programme for Research

Cloned livestock have potential importance in the provision of improved medicine as well as in the development of livestock production. The public is, however, increasingly concerned about the social and ethical consequences of these advances in knowledge and techniques. There is unevenness throughout Europe in different Member States' attitudes to research into livestock cloning. Although there is EU legislation controlling the use of animals for research purposes, there is no legislation specifically governing cloning in livestock production. The main EU reference is the 9th Opinion of the European Group on Ethics, which states "Cloning of farm animals may prove to be of medical and agricultural as well as economic benefit. It is acceptable only when the aims and methods are ethically justified and when carried out under ethical conditions." The ethical justification includes the avoidance of suffering, the use of the 3Rs principle and a lack of better alternatives. The Commission addresses these issues in the 6th Framework Programme by promoting the integration of ethical, legal and social aspects in all proposals where they are relevant, by fostering ethical awareness and foresight in the proposals, by encouraging public dialogue, and by supporting specific actions to promote the debate. Research must respect fundamental ethical principles, including animal welfare requirements.     

Comments on the sub-group reports of the EU Technical Expert Working Group on the revision of Directive 86/609/EEC on the protection of animals used for experimental and other scientific purposes

A critical analysis is presented of the reports produced by four Technical Expert Working Group Sub-groups (SGs) on Ethical Review, Cost-Benefit, Authorisation and Scope, which were published on the EC website (http://ec.europa.eu/environment/chemicals/lab_animals/ia_info_en.htm), as part of the European Commission (EC)s review of EU Directive 86/609 EEC. This is in addition to our official response to the internet consultation questionnaire, submitted to the Commission on behalf of FRAME. Whilst the respective SG reports were extensive and detailed, we have identified several shortcomings, and in particular, a frequent lack of consensus among the SG members, resulting in a lack of clear guidance for the EC on what the revised Directive should contain, with reference to a number of crucial issues. Such indecisiveness could lead to wide discrepancies in the approaches of the EC, the European Parliament and the EU Member States concerning many issues of importance to animal welfare and the implementation of alternatives to animal experiments. These concerns range from logistical issues, such as requirements for named officers in authorised establishments, and the recording and publishing of statistics on animal use, to ethical and scientific problems, including the use of non-human primates, local ethical review, and education and training on the essential link between the Three Rs concept and best scientific practice. In each case, the basis for our concerns is explained, and suggestions for improvements to be incorporated into the revised Directive are made, in the hope that the harmonisation of approaches to laboratory animal experimentation and the use of alternative methods in the Member States can be maximised.     

The European Federation of Organisations for Medical Physics Policy Statement No. 6.1: Recommended Guidelines on National Registration Schemes for Medical Physicists

This EFOMP Policy Statement is an update of Policy Statement No. 6 first published in 1994. The present version takes into account the European Union Parliament and Council Directive 2013/55/EU that amends Directive 2005/36/EU on the recognition of professional qualifications and the European Union Council Directive 2013/59/EURATOM laying down the basic safety standards for protection against the dangers arising from exposure to ionising radiation. The European Commission Radiation Protection Report No. 174, Guidelines on Medical Physics Expert and the EFOMP Policy Statement No. 12.1, Recommendations on Medical Physics Education and Training in Europe 2014, are also taken into consideration.The EFOMP National Member Organisations are encouraged to update their Medical Physics registration schemes where these exist or to develop registration schemes taking into account the present version of this EFOMP Policy Statement (Policy Statement No. 6.1“Recommended Guidelines on National Registration Schemes for Medical Physicists”).     

Dialogue and collaboration with ECVAM: the view of the EFPIA

An evaluation is presented of past experience of dialogue and collaboration of ECVAM with the European Federation of Pharmaceutical Industries and Associations (EFPIA) over the last nine years. Lessons learnt from the viewpoint of EFPIA company representatives are given. Also, proposals for the future ECVAM approach are made, such as support for other research areas for new methods to be validated, giving realistic statements to ECVAM's EU and external customers, and being open to any new technology development that might help in opening and establishing new alternative avenues. Finally, the need for proper publications on the implementation of alternatives is recommended, for example, through the existing national platforms and their umbrella organisation, ecopa.     

Convergence of EU nitrogen surplus,the RDP indicator of water quality

The EU Water Framework Directive (WFD), EU Nitrate Directive and EU Rural Development Policy (RDP) aim to improve water quality. The nutrient content of water can be decreased by reducing nitrogen emission. In this article a novel approach is applied to the evaluation of the impact of Agri Environmental Measures (AEM), which are part of axis 2 of the EU Rural Development Programme. The spending on AEM is linked to the reduction of nitrogen surplus, and hence, to the improvement of water quality. Reduction of nitrogen surplus is considered as a beta convergence process, in which the nitrogen surplus of EU member states converges to a steady state level. The convergence is tested, applying spatial econometrics on a panel data set of EU member states. The development over time of nitrogen surplus is explained applying the conditional beta convergence methodology. To allow for varying steady state nitrogen surpluses, structural variables are added to the analysis. RDP spending on AEM was added as structural variable to evaluate whether they affect the reduction of nitrogen surplus. The fixed effects panel data specification was tested to be the best model and preferred over spatial econometric specifications. A significantly negative effect is found between AEM expenditures and nitrogen surplus. Based on these estimation results it can be concluded that spending on AEM affects the convergence of nitrogen surplus towards a steady state level. A causal relationship cannot be tested with data on EU Member State level and additional analysis at smaller spatial level is warranted.     

An overall strategy for the testing of chemicals for human hazard and risk assessment under the EU REACH system

In its White Paper, "Strategy for a Future Chemicals Policy," published in 2001, the European Commission (EC) proposed the REACH (Registration, Evaluation and Authorisation of CHemicals) system to deal with both existing and new chemical substances. This system is based on a top-down approach to toxicity testing, in which the degree of toxicity information required is dictated primarily by production volume (tonnage). If testing is to be based on traditional methods, very large numbers of laboratory animals could be needed in response to the REACH system, causing ethical, scientific and logistical problems that would be incompatible with the time-schedule envisaged for testing. The EC has emphasised the need to minimise animal use, but has failed to produce a comprehensive strategy for doing so. The present document provides an overall scheme for predictive toxicity testing, whereby the non-animal methods identified and discussed in a recent and comprehensive ECVAM document, could be used in a tiered approach to provide a rapid and scientifically justified basis for the risk assessment of chemicals for their toxic effects in humans. The scheme starts with a preliminary risk assessment process (involving available information on hazard and exposure), followed by testing, based on physicochemical properties and (Q)SAR approaches. (Q)SAR analyses are used in conjunction with expert system and biokinetic modelling, and information on metabolism and identification of the principal metabolites in humans. The resulting information is then combined with production levels and patterns of use to assess potential human exposure. The nature and extent of any further testing should be based strictly on the need to fill essential information gaps in order to generate adequate risk assessments, and should rely on non-animal methods, as far as possible. The scheme also includes a feedback loop, so that new information is used to improve the predictivity of computational expert systems. Several recommendations are made, the most important of which is that the European Union (EU) should actively promote the improvement and validation of (Q)SAR models and expert systems, and computer-based methods for biokinetic modelling, since these offer the most realistic and most economical solution to the need to test large numbers of chemicals.     

An overall strategy for the testing of chemicals for human hazard and risk assessment under the EU REACH system

In its White Paper, Strategy for a Future Chemicals Policy, published in 2001, the European Commission (EC) proposed the REACH (Registration, Evaluation and Authorisation of CHemicals) system to deal with both existing and new chemical substances. This system is based on a top-down approach to toxicity testing, in which the degree of toxicity information required is dictated primarily by production volume (tonnage). If testing is to be based on traditional methods, very large numbers of laboratory animals could be needed in response to the REACH system, causing ethical, scientific and logistical problems that would be incompatible with the time-schedule envisaged for testing. The EC has emphasised the need to minimise animal use, but has failed to produce a comprehensive strategy for doing so. The present document provides an overall scheme for predictive toxicity testing, whereby the non-animal methods identified and discussed in a recent and comprehensive ECVAM document, could be used in a tiered approach to provide a rapid and scientifically justified basis for the risk assessment of chemicals for their toxic effects in humans. The scheme starts with a preliminary risk assessment process (involving available information on hazard and exposure), followed by testing, based on physicochemical properties and (Q)SAR approaches. (Q)SAR analyses are used in conjunction with expert system and biokinetic modelling, and information on metabolism and identification of the principal metabolites in humans. The resulting information is then combined with production levels and patterns of use to assess potential human exposure. The nature and extent of any further testing should be based strictly on the need to fill essential information gaps in order to generate adequate risk assessments, and should rely on non-animal methods, as far as possible. The scheme also includes a feedback loop, so that new information is used to improve the predictivity of computational expert systems. Several recommendations are made, the most important of which is that the European Union (EU) should actively promote the improvement and validation of (Q)SAR models and expert systems, and computer-based methods for biokinetic modelling, since these offer the most realistic and most economical solution to the need to test large numbers of chemicals.     

ECVAM,ECETOC and the EU chemicals policy

ECVAM's initiatives in validation have received significant support from the European Centre for Ecotoxicology and Toxicology of Chemicals (ECETOC), especially through the provision of reference chemical data banks, which contain peer-reviewed, high-quality in vivo data on commercially available chemical substances. Chemicals have been selected from these ECETOC data banks for validation studies on alternative methods for skin corrosion and irritation and for eye irritation and, in addition, an ECETOC task force peer-reviewed the selection and classification, on the basis of in vivo data, of chemicals used in the validation of three alternative methods for developmental toxicity. More recently, ECVAM and ECETOC have been pursuing parallel initiatives on the proposed new EU chemicals policy, with the common goals of ensuring that industry and European Commission resources are used to investigate only those chemicals that pose a significant risk to human health and the environment, and that the Policy requires that any testing which is required follows the Three Rs principles of reduction, refinement and replacement.     

Health consequences of Chernobyl and other radiation accidents

The Radiation Protection Research Unit of the European Commission has been supporting collaborative research projects on the radiological consequences of the Chernobyl accident since 1991. However, in the Fourth Framework Programme of the Commission which started in 1996, the collaboration with scientists in the former Soviet Union has been placed on a different footing, and the programme has been expanded to include other regions, especially in Russia and Kazakhstan, where previous nuclear incidents have led to the exposure of workers and the local populations and to widespread radioactive contamination. There are 15 projects on health-related studies in the newly started programme, and in order to improve the collaboration between the different scientists working in these projects a Cluster Contractors' Meeting was organised in San Miniato, Italy, in June 1997 with the participation of some 50 scientists from the European Union (EU) and the Newly Independent States (NIS). This report summarizes the different topics, including molecular biology and treatment of childhood thyroid cancer, various epidemiological studies and dose reconstruction, which were discussed at the meeting and which form the major projects in the new collaborative programme. Received: 1 November 1997 / Accepted in revised form: 10 December 1997     

Metabolism-mediated neurotoxicity: the significance of genetically engineered cell lines and new three-dimensional cell cultures

Until now, no in vitro methods for determining neurotoxic effects, on Phase I and Phase II biotransformation-driven metabolite formation or for the evaluation of the metabolism-mediated hazard of a chemical, have been validated. The current test guidelines are based on studies in vivo, involving animals exposed to the test substance. Novel in vitro testing instead of animal testing is required by Directive 86/609/EEC. In the EU White Paper on a Strategy for a Future Chemicals Policy, which may result in up to 20,000 chemicals being screened for toxicity, the use of non-animal test methods is seen as essential and is encouraged. The aim of the present work was to demonstrate the significance of novel technologies, including the use of genetically engineered cell lines and three-dimensional cell culture techniques for direct application in the regulatory hazard-assessment process. Furthermore, attempts were made to make in vitro toxicity tests for specific applications more-readily available for inclusion in the chemical hazard-assessment process, by exploiting advances made in the life sciences.     

欧盟Biocircle项目策略分析及对中国国际合作项目的启示

欧盟第七框架计划是当今世界上最大的官方重大科技合作计划,其研究以国际前沿和竞争性科技难点为主要内容,具有研究水平高、涉及领域广、投资力度大、参与国家多等特点.Biocircle项目是隶属于欧盟第七框架计划,参与国家24个,是一项国家联络点建设项目.通过介绍欧盟Biocircle国际合作项目,分析了欧盟国际合作项目的优势,并指出中国国际合作计划要更加主动更加开放,以期为中国的生物技术产业乃至于科技领域带来更多更好的促进机会.     

European Union research and innovation perspectives on biotechnology

“Food, Agriculture and Fisheries and Biotechnology” is one of 10 thematic areas in the Cooperation programme of the European Union's 7th Framework Programme for Research, Technological Development and Demonstration Activities (FP7). With a budget of nearly €2 billion for the period 2007–2013, its objective is to foster the development of a European Knowledge-Based Bio-Economy (KBBE) by bringing together science, industry and other stakeholders that produce, manage or otherwise exploit biological resources. Biotechnology plays an important role in addressing social, environmental and economic challenges and it is recognised as a key enabling technology in the transition to a green, low carbon and resource-efficient economy. Biotechnologies for non-health applications have received a considerable attention in FP7 and to date 61 projects on industrial, marine, plant, environmental and emerging biotechnologies have been supported with a contribution of €262.8 million from the European Commission (EC). This article presents an outlook of the research, technological development and demonstration activities in biotechnology currently supported in FP7 within the Cooperation programme, including a brief overview of the policy context.     

European Union research and innovation perspectives on biotechnology

"Food, Agriculture and Fisheries and Biotechnology" is one of 10 thematic areas in the Cooperation programme of the European Union's 7th Framework Programme for Research, Technological Development and Demonstration Activities (FP7). With a budget of nearly €2 billion for the period 2007-2013, its objective is to foster the development of a European Knowledge-Based Bio-Economy (KBBE) by bringing together science, industry and other stakeholders that produce, manage or otherwise exploit biological resources. Biotechnology plays an important role in addressing social, environmental and economic challenges and it is recognised as a key enabling technology in the transition to a green, low carbon and resource-efficient economy. Biotechnologies for non-health applications have received a considerable attention in FP7 and to date 61 projects on industrial, marine, plant, environmental and emerging biotechnologies have been supported with a contribution of €262.8 million from the European Commission (EC). This article presents an outlook of the research, technological development and demonstration activities in biotechnology currently supported in FP7 within the Cooperation programme, including a brief overview of the policy context.     

Development and prevalidation of a list of structure-activity relationship rules to be used in expert systems for prediction of the skin-sensitising properties of chemicals

The new European Union (EU) chemicals policy, as described in the White Paper entitled Strategy for a Future Chemicals Policy, has identified a need for computer-based tools suitable for predicting the hazardous properties of chemicals. Two sets of structural alerts (fragments of chemical structure) for the prediction of skin sensitisation hazard classification ("R43, may cause sensitisation by skin contact") have been drawn up, based on sensitising chemicals from a regulatory database (containing data for the EU notification of new chemicals). These alerts comprise 15 rules for chemical structures deemed to be sensitising by direct action of the chemicals with cells or proteins within the skin, and three rules for substructures that act indirectly, i.e. requiring chemical or biochemical transformation. The predictivity rates of the rules were found to be good (positive predictivity, 88%; false-positive rate, 1%; specificity, 99%; negative predictivity, 74%; false-negative rate, 80%; sensitivity, 20%). Because of the confidential nature of the regulatory database, the rules are supported by examples of sensitising chemicals taken from the "Allergenliste" now held by the Federal Institute for Risk Assessment (BfR) and the DEREK for Windows expert system. The rules were prevalidated against data not used for their development. As a result of the prevalidation study, it is proposed that the two sets of structural alerts should be taken forward for formal validation, with a view to incorporating them into regulatory guidelines.