Registration, Evaluation And Authorisation Of Chemicals Research Articles

A Category Approach for Reproductive Effects of Phthalates

In regulatory toxicology, the experimental assessment of reproductive toxicity is one of the most costly endpoints to perform. Categorizing chemicals is an approach that can be used to reduce animal tests in risk assessments of chemicals, for example, via REACH (Registration, Evaluation, and Authorization of Chemicals). The category approach was tested for reproductive toxicity with a group of 10 ortho-phthalate esters, with different side chain lengths. Three ortho-phthalates were used for testing the category. Phthalates with side-chain lengths C4 to C6 that are commonly known to cause reproductive effects were included, as well as the recently discovered mechanism that indicates antiandrogenic effects. The differences in physicochemical properties, absorption rates, and metabolism between the phthalates investigated could not fully explain the difference in reproductive toxicity. It was concluded that phthalates with the alkyl side-chain length from C4 to C6 produce similar severe reproductive effects in experimental animals. It is expected that phthalates included in the tight boundaries of the proposed category would all show severe reproductive effects, especially the antiandrogenic effects. Further testing might not be needed for phthalates within these boundaries. If necessary, limited testing could focus on the critical endpoints. Detailed mechanistic information is needed on phthalates to apply the categories for regulatory toxicology.

Rethinking the role of information in chemicals policy: implications for TSCA and REACH

This article analyses the role of different kinds of information for minimizing or eliminating the risks due to the production, use, and disposal of chemical substances and contrasts it with present and planned (informational) regulation in the United States and the European Union, respectively. Some commentators who are disillusioned with regulatory approaches have argued that informational tools should supplant mandatory regulatory measures unflatteringly described as “command and control.” Critics of this reformist view are concerned with the lack of technology-innovation forcing that results from informational policies alone. We argue that informational tools can be made more technology inducing – and thus more oriented towards environmental innovations – than they are under current practices, with or without complementary regulatory mechanisms, although a combination of approaches may yield the best results. The conventional approach to chemicals policy envisions a sequential process that includes three steps of (1) producing or collecting risk-relevant information, (2) performing a risk assessment or characterization, followed by (3) risk management practices, often driven by regulation. We argue that such a sequential process is too static, or linear, and spends too many resources on searching for, or generating information about present hazards, in comparison to searching for, and generating information related to safer alternatives which include input substitution, final product reformulation, and/or process changes. These pollution prevention or cleaner technology approaches are generally acknowledged to be superior to pollution control. We argue that the production of risk information necessary for risk assessment, on the one hand, and the search for safer alternatives on the other hand, should be approached simultaneously in two parallel quests. Overcoming deficits in hazard-related information and knowledge about risk reduction alternatives must take place in a more synchronized manner than is currently being practiced. This parallel approach blurs the alleged bright line between risk assessment and risk management, but reflects more closely how regulatory agencies actually approach the regulation of chemicals. These theoretical considerations are interpreted in the context of existing and planned informational tools in the United States and the European Union, respectively. The current political debate in the European Union concerned with reforming chemicals policy and implementing the REACH ( Registration, Evaluation and Authorization of Chemicals) system is focused on improving the production and assessment of risk information with regard to existing chemicals, although it also contains some interesting risk management elements. To some extent, REACH mirrors the approach taken in the United States under the Toxics Substances Control Act (TSCA) of 1976. TSCA turned out not to be effectively implemented and provides lessons that should be relevant to REACH. In this context, we discuss the opportunities and limits of existing and planned informational tools for achieving risk reduction.

Policy: Framing a Chemical Future

Vol. 113, No. 7 EnvironewsOpen AccessPolicy: Framing a Chemical Future Richard Dahlz Richard Dahlz Search for more papers by this author Published:1 July 2005https://doi.org/10.1289/ehp.113-a450bAboutSectionsPDF ToolsDownload CitationsTrack Citations ShareShare onFacebookTwitterLinked InReddit Spurred by recent developments abroad to design new approaches to chemical management, the University of Massachusetts Low-ell Center for Sustainable Production sponsored a two-day conference in April 2005 to stimulate similar productive changes in the United States. The event attracted a mix of some 170 environmentalists, government officials, academics, product representatives, and chemical industry representatives.The conference aimed to initiate the kind of multi-stakeholder dialogue that the European Commission created in the late 1990s. The European effort has resulted in a draft regulation called REACH (Registration, Evaluation and Authorisation of Chemicals), which calls for manufacturers and importers to identify and report the properties of the substances they use and sell. Other international actions, such as the 2002 World Summit on Sustainable Development, which set a goal of achieving sound global management of chemicals by 2020, have also heightened the need for better U.S. chemical policies. Discussions begun at this workshop may eventually lead to public policy supporting a safer and more competitive U.S. chemical industry.Speakers opened the meeting with talks on the current thinking of chemical policy as well as specific policies and industrial protocols. Then participants broke out into workshops on various subjects. One group focused on the promotion of innovative industry initiatives, “green chemistry,” and alternative materials. Others dealt with improving information flows in supply chains and beyond, integration of U.S. and global chemical initiatives, and incorporation of improved chemicals management into business processes.One theme repeated throughout the conference was the need for improved communication about what’s in the products that people buy, and greater transparency of the people who make the products. “The thing that I really noticed about [participant feedback] was the importance that people placed on information—the flow of information, the access to information, who’s responsible, where it’s stored,” said center director Kenneth Geiser.A second repeating theme was support for green chemistry, chemical processes that reduce or eliminate the use and generation of hazardous substances in economically viable ways. Paul Anastas, director of the Green Chemistry Institute in Washington, DC, said he noticed a recognition that such scientific innovations “can be both economically profitable and environmentally preferable.”Geiser said there also was nearly universal agreement by participants that the current U.S. chemicals policy, largely embodied in the Toxic Substances Control Act of 1976, is outdated. “Almost everyone I talked to felt that the current chemicals policy system needs overhauling,” he said. “It’s interesting that the business folks felt the same way; it’s not working for them, either.”The Lowell Center will compile a report on the conference in the next few months. Geiser believes the conference’s goal has been met. “I think we created an enthusiasm for moving forward,” he said. “That was pretty much what we wanted.”FiguresReferencesRelatedDetails Vol. 113, No. 7 July 2005Metrics About Article Metrics Publication History Originally published1 July 2005Published in print1 July 2005 Financial disclosuresPDF download License information EHP is an open-access journal published with support from the National Institute of Environmental Health Sciences, National Institutes of Health. All content is public domain unless otherwise noted. Note to readers with disabilities EHP strives to ensure that all journal content is accessible to all readers. However, some figures and Supplemental Material published in EHP articles may not conform to 508 standards due to the complexity of the information being presented. If you need assistance accessing journal content, please contact [email protected]. Our staff will work with you to assess and meet your accessibility needs within 3 working days.

DRY RUN FOR EU'S REACH PROGRAM

THE EUROPEAN UNION'S PENDing legislation on the registration, evaluation, and authorization of chemicals (REACH) is moving through the final stages of its formulation. Though the legislation is controversial, some version of REACH is expected to take effect in two years or so. In the meantime, the European chemical industry and the governments of both the EU and its member states are starting to prepare for implementation of REACH. To do so, they are working together to test the workability of the registration of chemicals, to see how REACH might actually operate, and to identify solutions to any problems before the legislation is enacted. The European Commission—which is the EU's executive branch—several member states, and chemical companies recently conducted a pilot run of how chemicals will get registered under REACH. The project, called the Strategic Partnership on REACH Testing (SPORT), is the brainchild of the European Chemical Industry Council, says Lena Perenius, director of ...

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The U.S. Experience in Promoting Sustainable Chemistry (9 pp)

Recent developments in European chemicals policy, including the Registration, Evaluation and Authorization of Chemicals (REACH) proposal, provide a unique opportunity to examine the U.S. experience in promoting sustainable chemistry as well as the strengths and weaknesses of existing policies. Indeed, the problems of industrial chemicals and limitations in current regulatory approaches to address chemical risks are strikingly similar on both sides of the Atlantic. We provide an overview of the U.S. regulatory system for chemicals management and its relationship to efforts promoting sustainable chemistry. We examine federal and state initiatives and examine lessons learned from this system that can be applied to developing more integrated, sustainable approaches to chemicals management. There is truly no one U.S. chemicals policy, but rather a series of different un-integrated policies at the federal, regional, state and local levels. While centerpiece U.S. Chemicals Policy, the Toxic Substances Control Act of 1976, has resulted in the development of a comprehensive, efficient rapid screening process for new chemicals, agency action to manage existing chemicals has been very limited. The agency, however, has engaged in a number of successful, though highly underfunded, voluntary data collection, pollution prevention, and sustainable design programs that have been important motivators for sustainable chemistry. Policy innovation in the establishment of numerous state level initiatives on persistent and bioaccumulative toxics, chemical restrictions and toxics use reduction have resulted in pressure on the federal government to augment its efforts. It is clear that data collection on chemical risks and phase-outs of the most egregious chemicals alone will not achieve the goals of sustainable chemistry. These alone will also not internalize the cultural and institutional changes needed to ensure that design and implementation of safer chemicals, processes, and products are the focus of the future. Thus, a more holistic approach of 'carrots and sticks'--that involves not just chemical producers but those who use and purchase chemicals is necessary. Some important lessons of the US experience in chemicals management include: (1) the need for good information on chemicals flows, toxic risks, and safer substances.; (2) the need for comprehensive planning processes for chemical substitution and reduction to avoid risk trade-offs and ensure product quality; (3) the need for technical and research support to firms for innovation in safer chemistry; and (4) the need for rapid screening processes and tools for comparison of alternative chemicals, materials, and products.

Rethinking the Role of Information in Chemicals Policy: Implications for TSCA and REACH

This article analyzes the role of different kinds of information for minimizing or eliminating the risks due to the production, use, and disposal of chemical substances and contrasts it with present and planned (informational) regulation in the United States and the European Union, respectively. Some commentators who are disillusioned with regulatory approaches have argued that informational tools should supplant mandatory regulatory measures unflatteringly described as “command and control.” Critics of this reformist view are concerned with the lack of technology-innovation forcing that results from informational policies alone. We argue that informational tools can be made more technology inducing – and thus more oriented towards environmental innovations – than they are under current practices, with or without complementary regulatory mechanisms, although a combination of approaches may yield the best results. The conventional approach to chemicals policy envisions a sequential process that includes three steps of (1) producing or collecting risk-relevant information, (2) performing a risk assessment or characterization, followed by (3) risk management practices, often driven by regulation. We argue that such a sequential process is too static, or linear, and spends too many resources on searching for, or generating information about present hazards, in comparison to searching for, and generating information related to safer alternatives which include input substitution, final product reformulation, and/or process changes. These pollution prevention or cleaner technology approaches are generally acknowledged to be superior to pollution control. We argue that the production of risk information necessary for risk assessment, on the one hand, and the search for safer alternatives on the other hand, should be approached simultaneously in two parallel quests. Overcoming deficits in hazard-related information and knowledge about risk reduction alternatives must take place in a more synchronized manner than is currently being practiced. This parallel approach blurs the alleged bright line between risk assessment and risk management, but reflects more closely how regulatory agencies actually approach the regulation of chemicals. These theoretical considerations are interpreted in the context of existing and planned informational tools in the United States and the European Union, respectively. The current political debate in the European Union concerned with reforming chemicals policy and implementing the REACH (Registration, Evaluation and Authorization of Chemicals) system is focused on improving the production and assessment of risk information with regard to existing chemicals, although it also contains some interesting risk management elements. To some extent, REACH mirrors the approach taken in the U.S. under the Toxics Substances Control Act (TSCA) of 1976. TSCA turned out not to be effectively implemented and provides lessons that should be relevant to REACH. In this context, we discuss the opportunities and limits of existing and planned informational tools for achieving risk reduction.

The role of the European centre for the validation of alternative methods (ECVAM) in the validation of (Q)SARs

Under the current chemicals legislation, the regulatory use of structure-activity relationships (SARs) and quantitative structure-activity relationships (QSARs), collectively referred to as (Q)SARs, for the assessment of chemicals is limited, partly due to concerns about the extent to which (Q)SAR estimates can be relied upon. On 29 October 2003, the European Commission adopted a legislative proposal that foresees the introduction of a new regulatory system for chemicals called REACH (Registration, Evaluation, and Authorisation of Chemicals), which will impose equivalent information requirements on both new and existing chemicals. For reasons of practicality, cost-effectiveness and animal welfare, it is envisaged that (Q)SARs will play an important role in the assessment of some 30,000 existing chemicals for which further information may be required under the REACH system. It will therefore be essential that the (Q)SAR models used will produce reliable estimates. To overcome the barriers in the acceptance of (Q)SARs for regulatory purposes, it is widely acknowledged that there needs to be international agreement on the principles of (Q)SAR validation, and that the process of (Q)SAR validation should be managed by independent organisations, with a view to providing independent advice to the regulators who make decisions on the acceptability of (Q)SARs. The European Centre for the Validation of Alternative Methods (ECVAM), which is part of the European Commission's Joint Research Centre (JRC), has a well-established role in providing independent scientific and technical advice to European policy makers. This paper describes progress made at an international level regarding the principles of validation, and explains the role of ECVAM regarding the practical validation of (Q)SARs.

Regulatory assessment for chemicals: a rapid appraisal cost–benefit approach

Abstract The purpose of this paper is to explore alternative ‘rapid appraisal’ methodologies for determining the costs and benefits of environmental legislation, the focus being the new Chemicals Policy in the European Union (EU) known as REACH (Registration, Evaluation and Authorisation of Chemicals). We show that a full and rigorous cost–benefit appraisal of this legislation is not possible because of informational deficiencies. Hence, some ‘second best’ approach is required. In addition, full cost–benefit appraisal is likely to be expensive and impossible to conduct in the near-term. We argue that it is possible to obtain some broad estimates of gains and losses by making reasonable assumptions and by pursuing different methodologies for estimating benefits. Two methodologies, both based on the notion of a disability-adjusted life year (DALY), are adopted. A DALY is a measure of health loss, enabling different forms of morbidity to be compared with premature mortality. We seek to ‘monetise’ DALYs in order to make a direct comparison with the costs of the policy measures. The first approach addresses health expenditure in the UK and EU, based on the presumption that this expenditure is incurred in order to avoid and treat the causes of DALYs. Health expenditure per DALY is thus a measure of the value of a DALY and this expenditure is avoided by reductions in DALYs due to environmental control. The second approach assigns a willingness-to-pay value to a DALY based on an ‘anchor’ estimate of the ‘value of a statistical life’ (VOSL) and an implied value of a ‘life year’ (VOLY). On the basis of these models we show that while the costs of REACH could be greater than benefits, the second approach reveals a strong probability that benefits exceed costs. Since our models explicitly exclude any environmental benefits, we regard our benefit estimates as minima. Overall, our own judgement is that we feel confident that REACH generates net benefits, a result consistent with other partial studies that have been carried out to date.

A Scientific and Animal Welfare Assessment of the OECD Health Effects Test Guidelines for the Safety Testing of Chemicals under the European Union REACH System

We have assessed each of the OECD Health Effects Test Guidelines (TGs) that were included in an annex to the Internet consultation issued by the European Commission relating to the Registration, Evaluation and Authorisation of Chemicals (REACH) legislation for the testing of new and existing chemical substances. Each guideline has been analysed with respect to its design and its scientific and animal welfare implications, the extent to which it makes use of modern techniques, and its suitability to be used in the REACH system for the testing of large numbers of chemicals. The scientific basis of the test and its justification are considered, as well as the numbers of animals required, and the potential adverse effects on them. The prospects and possibilities for applying the Three Rs (reduction, refinement and replacement) to each of the TGs are also discussed. We have proposed an overall testing strategy for how these TGs and other methods could best be deployed for chemicals testing, should it be necessary to fill data gaps. Certain TGs have been omitted from the strategy, when we have considered them to be unnecessary for chemicals testing. A series of recommendations has been made for improving the TGs with regard to both their scientific content and ways in which they could be better designed in relation to optimising the use of the animals concerned, and minimising adverse welfare consequences to them. Our investigations show that there is an urgent need to update the TGs to reflect modern techniques and methods, and to use current approaches for applying refinement strategies to improve the scientific and animal welfare aspects of the procedures used. Improvements can and should be made in all aspects of toxicity testing, from sample preparation, and animal housing, care and feeding, to dose formulation, test material administration, and the histopathological and clinical analysis of tissue samples. Opportunities for streamlining individual assays are very limited, but testing could be made more efficient by: a) only undertaking studies that provide relevant data; b) making greater use of screens and preliminary testing; c) applying some tests simultaneously to the same animals; d) using one sex; and e) eliminating redundant tests. In conclusion, it is clear that, as they stand, the OECD Health Effects TGs are unsuitable for use in the European Union REACH system, for which potentially very large numbers of laboratory animals will be needed for the testing of a very large number of chemicals.

POSSIBLE DISPUTE OVER EU POLICY

THE EUROPEAN UNION'S PROPOSED regulatory scheme for chemicals continues to worry chemical makers in the U.S. and elsewhere. Much of this concern has focused on whether and how industry will be able to comply with the planned registration, evaluation, and authorization of chemicals (REACH) program-and what the cost will be. Now, industry is beginning to raise a new set of arguments, one that could lift the debate into the global arena of the World Trade Organization. The American Chemistry Council (ACC) says parts of REACH may conflict with international trade rules because the proposal contains provisions that could lead to a formal trade dispute. The European Commission-the administrative arm of the EU-insists that REACH has undergone rigorous review for compliance with WTO regulations. And environmental groups characterize ACCs arguments solely as a tactic to delay or weaken REACH before the plan is finalized. The European Parliament is expected to complete a final version of the ...

The Case for Taking Account of Metabolism when Testing for Potential Endocrine Disruptors In Vitro

Legislation in the USA, Europe and Japan will require that chemicals are tested for their ability to disrupt the hormonal systems of mammals. Such chemicals are known as endocrine disruptors (EDs), and will require extensive testing as part of the new European Union Registration, Evaluation and Authorisation of Chemicals (REACH) system for the risk assessment of chemicals. Both in vivo and in vitro tests are proposed for this purpose, and there has been much discussion and action concerning the development and validation of such tests. However, to date, little interest has been shown in incorporating metabolism into in vitro tests for EDs, in sharp contrast to other areas of toxicity testing, such as genotoxicity, and, ironically, such in vitro tests are criticised for not modelling in vivo metabolism. This is despite the existence of much information showing that endogenous and exogenous steroids are extensively metabolised by Phase I and Phase II enzymes both in the liver and in hormonally active tissues. Such metabolism can lead to the activation or detoxification of steroids and EDs. The absence of metabolism from these tests could give rise to false-positive data (due to lack of detoxification) or false-negative data (lack of activation). This paper aims to explain why in vitro assays for EDs should incorporate mammalian metabolising systems. The background to ED testing, the test methods available, and the role of mammalian metabolism in the activation and detoxification of both endogenous and exogenous steroids, are described. The available types of metabolising systems are compared, and the potential problems in incorporating metabolising systems into in vitro tests for EDs, and how these might be overcome, are discussed. It is recommended that there should be: a) an assessment of the intrinsic metabolising capacity of cell systems used in tests for EDs; b) an investigation into the relevance of using the prostaglandin H synthase system for metabolising EDs; and c) a feasibility study into the generation of genetically engineered mammalian cell lines expressing specific metabolising enzymes, which could also be used to detect EDs.

The Problem of Current Toxic Chemicals Management

In this article, we explore the limitations of current chemicals management policies worldwide and the evolution of new European, International and U.S. policies to address the problem of toxic chemicals control. It is becoming increasingly apparent that current chemicals management policies in Europe and the United States are inadequate. There is a general lack of toxicity and exposure information on chemicals in commerce and the vast majority of chemicals were considered safe until proven guilty in legislation. Governments must then prove each chemical is dangerous through a slow and resource-intensive risk assessment process. For more than a decade, Nordic countries, such as Denmark and Sweden, have actively promoted integrated chemicals policies to address contamination of critical waterways. They have successfully used a variety of voluntary and mandatory policy tools, such as education, procurement, lists of chemicals of concern, eco-labeling, research and development on safer substitutes, and chemical phase-out requirements, to encourage companies using chemicals to reduce their reliance on harmful substances and to develop safer substitutes. While previously isolated to particular countries, innovative and exciting European-wide policies to promote sustainable chemicals management are now moving forward, including the recently published draft Registration, Evaluation and Authorization of CHemicals (REACH) policy of the European Union. A sweeping change in chemicals management policies in Europe is inevitable and it will ultimately affect manufacturers in the U.S. and globally. The European movement provides an opportunity to initiate a discussion on integrated chemicals policy in the U.S. where some innovative initiatives already are underway.

TestSmart and Toxic Ignorance

There are a number of national and international efforts designed to screen chemicals for toxicity. Although the emphasis in terms of the specific chemicals is different, e.g. endocrine disruptors, children's health, High Production Volume (HPV), the European Registration, Evaluation and Authorisation of Chemicals (REACH) programme, the purpose is the same. Each is intended to evaluate the potential toxicity of chemicals to humans and, in some cases, to the environment. How best can these tasks be accomplished? The first need is to provide a realistic prioritisation of which chemicals need to be evaluated. Once identified, a defined decision-tree approach with an emphasis on short-term in vitro assays and new genomic technologies offers the greatest promise. The more practical matter of screening the chemicals would be by using a tiered decision-tree approach. Common features of the approach would be the use of three tiers. The first tier would be a screening/prioritisation tier, the second would provide an initial characterisation of toxicity, and the third would discern mode of action/biological activity. The intent of this approach is to provide a concept that will allow decisions to be made as to which chemicals need to be tested, provide some idea as to their toxicity and finally mode of action, and at the same time, taking into account the Three Rs, reduction, refinement and replacement. Thus, specific batteries of tests are not discussed, as these would need to be tailored to the specific chemicals of concern, e.g. endocrine disruptors, HPV. Neither are regulatory requirements factored into the concept, but the data that would be gathered should consider the possibility of eventual submission of the data obtained by in vitro and other non-traditional approaches by regulatory authorities.

The Regulatory Acceptance of Alternatives in the European Union

Recently, progress has been made toward the regulatory acceptance of replacements in the European Union (EU), particularly with the introduction of in vitro methods for the prediction of skin corrosivity, dermal penetration, phototoxicity and embryotoxicity. In vitro genotoxicity tests are well established, and testing for this endpoint can be completed without animals, provided that clear negative outcomes are obtained. Tiered approaches including in vitro tests can also be used to address skin and eye irritation endpoints. Reductions and/or refinements in animal use are being achieved following the replacement of the oral LD50 test with alternative methods and the adoption of reduced test packages for materials, such as closed-system intermediates and certain polymers. Furthermore, the use of a "read-across" approach has reduced animal testing. Substantial gains in refinement will also be made with the recent acceptance of the local lymph node assay for skin sensitisation and the development of an acute inhalation toxicity method that avoids lethality as the endpoint. For the future, under the proposed EU Registration, Evaluation and Authorisation of Chemicals (REACH) scheme, it is envisaged that, where suitable in vitro methods exist, these should be used to support registration of substances produced at up to ten tonnes per annum. This proposal can only accelerate the further development, validation and regulatory acceptance of such alternative methods.

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.

FRAME and the Royal Commission on Environmental Pollution: Common Recommendations for Assessing Risks Posed by Chemicals under the EU REACH System

This document discusses recommendations made by FRAME and the Royal Commission on Environmental Pollution (RCEP) with regard to the current European Commission proposals on the Registration, Evaluation and Authorisation of Chemicals (REACH) system for assessing the risks of chemicals to humans, wildlife and the environment. Of several common aims and recommendations, the two most important are: a) the greater use of non-animal testing methods, especially computational prediction methods (for example, [quantitative] structure-activity relationships, expert systems and biokinetic modelling) for prioritising chemicals for hazard assessment; and b) the greater use of intelligent exposure-based targeted risk assessment, with less emphasis being placed on tonnage-triggers. FRAME has produced a decision-tree testing scheme to illustrate the way in which these approaches could be used, together with in vitro test methods. This scheme has been slightly modified to take account of proposals subsequently made by the RCEP. In addition, FRAME points out that new and improved computational methods are needed through more coordinated research, and that these and existing methods need to be validated. The similarities between the independent publications of FRAME and the RCEP add weight to the recommendations that each have made concerning the implementation of the REACH system.

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.

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.