ATLA 34.S1, March 2006

//ATLA 34.S1, March 2006

Comment – Four papers on the OECD Health Effects Test Guidelines

Michael Balls and Robert D. Combes
Angela Auletta
John E. Doe, Richard W. Lewis and Philip A. Botham
Barry Phillips

 

This post combines four papers:
The OECD Health Effects Test Guidelines: A Challenge to the Sincerity of Commitment to the Three Rs by Michael Balls and Robert D. Combes
An Assessment of Some Recommendations Made Concerning the OECD Health Effects Test Guidelines by Angela Auletta
Comments on 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 by John E. Doe, Richard W. Lewis and Philip A. Botham
and
OECD Test Guidelines are Tools, not Blueprints, for Chemical Safety Assessment by Barry Phillips

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Editorial: The EU REACH System: Opportunities and Threats

Michael Balls

In 2001, the European Commission (EC) issued a White Paper entitled Strategy for a Future Chemicals Policy,1 which was subsequently developed into a proposed system for the Registration, Evaluation, Authorisation and Restriction of Chemicals (REACH), to be applied to all chemicals manufactured and/or used in the European Union (EU), in order to ensure a high level of protection for human health and the environment.2 This move was prompted by concern that as many as 100,000 “existing” chemicals were already on the EU market before the current legislation concerning “new” chemicals came into force in September 1981.
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Introduction to the EU REACH Legislation

Christina Grindon and Robert Combes

FRAME initiatives on the European Union REACH (Registration, Evaluation and Authorisation of Chemicals) system for the safety testing and risk assessment of chemicals, first proposed as a White Paper in 2001, are summarised. These initiatives considered the scientific and animal welfare issues raised by the REACH proposals, and resulted in a number of suggestions for improvement, many of which seem to have been adopted during the current progress of the legislation through the European Council and European Parliament.
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Editorial: The EU White Paper: Strategy for a Future Chemicals Policy

Robert Combes

The publication in 2001 of a White Paper on a new European Union (EU) initiative, entitled Strategy for a Future Chemicals Policy,1 has caused great concern among scientists and animal welfare groups about a possibly huge increase in the use of
laboratory animals to cope with the further testing of some 30,000 existing chemicals in use in the EU. Also, a burden has been placed on chemical manufacturers and downstream users (for example, companies that use chemicals as ingredients in the manufacture of other products) to provide hazard data and to undertake separate risk assessments, as part of the overall process of risk management.
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An Overall Strategy for the Testing of Chemicals for Human Hazard and Risk Assessment under the EU REACH System

Robert Combes, Martin Barratt and Michael Balls

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.
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A Critical Assessment of the European Commission’s Proposals for the Risk Assessment and Registration of Chemical Substances in the European Union

Robert Combes, Jennifer Dandrea and Michael Balls

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.
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A Survey of Stakeholder Organisations on the Proposed New European Chemicals Policy

Jennifer Dandrea and Robert D. Combes

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

Robert D. Combes, Jennifer Dandrea and Michael Balls

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–ac ivity 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.
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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

Robert D. Combes, Ian Gaunt and Michael Balls

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.
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Editorial: The EU REACH System: Blessing in Disguise or Wolf in Wolf’s

Nirmala Bhogal

For many years, caveats in the existing EU legislation for chemical testing have allowed a substantial number of chemicals with ill-defined human health or environmental effects to be produced in or imported into Europe. Amidst growing public concern, EU legislators have formulated a new European chemicals policy in the form of the Registration, Evaluation and Authorisation of Chemicals (REACH) system, which aims to ensure the protection of human health and the environment, maintain the competitiveness of the European chemical industry, and prevent fragmentation of the internal market. REACH has now been approved in principle by the European Parliament and the European Council, and could be in force by 2007.
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2017-01-09T06:37:02+00:00 Tags: |