Flows of Chemical Risk Information in the Consumer Paint Product Chain

In this study the flows of chemical risk information for paint as a consumer product were investigated from a product chain perspective. The main method of research involved semi‐structured interviews with Swedish manufacturers of paint and chemicals. In addition, retailers and consumers were interviewed. The flows of chemical risk information between actors within (e.g., manufacturers, retailers, and consumers) and outside (e.g., industry associations and regulators) the paint product chain are described. Because the European chemical legislation REACH (Registration, Evaluation, Authorization and restriction of CHemicals) plays a large role in the management of chemical risk information at companies, some consequences of REACH on actors in the paint product chain are described. Examples of such consequences are that importing of chemicals from non–European Union (EU) countries may be discouraged and that some low‐volume chemicals may no longer be produced. However, manufacturers do not yet see these consequences as impediments to innovation. The results of this work show that chemical risk information is most comprehensive during the manufacturing steps of the product chain. This is due not only to tradition and industry initiatives, but also to REACH and other legislation. The results also illustrate the need for evaluation of how chemical risk information is used in different contexts and the importance of directing the right information at the right target group. Following legislative development, more specialized information is required in the safety data sheet (SDS), and because of this many manufacturers find it necessary to create simplified safety sheets that make the most pertinent safety and hazard information easily accessible to individuals that handle the chemicals in their factories. The study found that in creating the simplified safety sheets, the content and use of chemical risk information is evaluated and adjusted for presentation to this particular target group. It is evident that the Swedish Paint and Printing Ink Makers Association plays an important role in the interpretation of legal requirements and even in agreements for providing information that exceeds legal requirements.     

A review of the status of alternative approaches to animal testing and the development of integrated testing strategies for assessing the toxicity of chemicals under REACH--a summary of a DEFRA-funded project conducted by Liverpool John Moores University and FRAME

Liverpool John Moores University and FRAME were recently awarded a DEFRA tender to conduct a review of the status of alternative approaches to animal testing, and to recommend further research with regard to the forthcoming European Union REACH (Registration, Evaluation and Authorisation of Chemicals) system for the safety testing and risk assessment of chemicals. The outcome of the project is summarised, including the prospects for in vitro and in silico testing, areas where reduction and refinement could be applied, and how decision-tree integrated testing strategies could be used to reduce the number of animals needed to fulfil the testing requirements of the REACH system. This paper is a prelude to a series of individual papers on detailed suggestions for applying non-animal methods to each of the major toxicity endpoints in REACH.     

Improving structure and transparency in reliability evaluations of data under REACH: suggestions for a systematic method

Abstract

The goal of identifying hazardous chemicals registered under the Registration, Evaluation, Authorization and restriction of CHemicals (REACH) Regulation and taking appropriate risk management measures relies on robust data registrations. However, the current procedures for European chemical manufacturers and importers to evaluate data under REACH neither support systematic evaluations of data nor transparently communicate these assessments. The aim of this study was to explore how using a data evaluation method with predefined criteria for reliability and establishing principles for assigning reliability categories could contribute to more structured and transparent evaluations under REACH. In total, 20 peer-reviewed studies for 15 substances registered under REACH were selected for an in-depth evaluation of reliability with the SciRAP tool. The results show that using a method for study evaluation, with clear criteria for assessing reliability and assigning studies to reliability categories, contributes to more structured and transparent reliability evaluations. Consequently, it is recommended to implement a method for evaluating data under REACH with predefined criteria and fields for documenting and justifying the assessments to increase consistency of data evaluations and transparency.     

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.     

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.     

On the Use of Mixture Toxicity Assessment in REACH and the Water Framework Directive: A Review

This review seeks to connect the scientific theory of mixture toxicity to its implementation within different regulatory frameworks. The aim is to demonstrate how mixture toxicity assessment can be more thoroughly integrated into the European chemical regulations, REACH, and the Water Framework Directive (WFD), using the experiences gained through other regulatory frameworks. The article consists of (1) an examination of the scientific underpinnings of the common mixture toxicity assessment methods; (2) a discussion of how these methods have been used in regulatory frameworks; and (3) a discussion of how the methods could be applied within REACH and the WFD. It is concluded that concentration addition should be applied as a default model for mixture toxicity assessment. Furthermore, it is concluded that REACH and the WFD only include mixture toxicity assessments in specific situations. However, it is shown that it is scientifically feasible and regulatorally practicable to integrate a more holistic mixture toxicity approach into both legislations. In this connection, the experience gained from the U.S. frameworks on mixture toxicity assessment could be useful. The construction of a database that includes data on chemicals in the European environment could be used for mixture toxicity assessment of the chemicals with individual PEC/PNECs > 0.1.     

Integrated decision-tree testing strategies for skin corrosion and irritation with respect to the requirements of the EU REACH legislation

Liverpool John Moores University and FRAME recently conducted a research project, sponsored by DEFRA, on the status of alternatives to animal testing with regard to the European Union REACH (Registration, Evaluation and Authorisation of Chemicals) system for the safety testing and risk assessment of chemicals. The project covered all the main toxicity endpoints associated with the REACH system. This report focuses on how to maximise the use of alternative methods (both in vitro and in silico) for skin corrosion and irritation testing within a tiered testing strategy. It considers the latest developments in in vitro testing, with particular reference to the reconstituted skin models which have now been now been successfully validated and independently endorsed as suitable for both skin corrosivity and irritancy testing within the EU.     

Integrated decision-tree testing strategies for acute systemic toxicity and toxicokinetics with respect to the requirements of the EU REACH legislation

Liverpool John Moores University and FRAME conducted a joint research project, sponsored by Defra, on the status of alternatives to animal testing with regard to the European Union REACH (Registration, Evaluation and Authorisation of Chemicals) system for the safety testing and risk assessment of chemicals. The project covered all the main toxicity endpoints associated with REACH. This paper focuses on the use of alternative (non-animal) methods (both in vitro and in silico) for acute systemic toxicity and toxicokinetic testing. The paper reviews in vitro tests based on basal cytotoxicity and target organ toxicity, along with QSAR models and expert systems available for this endpoint. The use of PBPK modelling for the prediction of ADME properties is also discussed. These tests are then incorporated into a decision-tree style, integrated testing strategy, which also includes the use of refined in vivo acute toxicity tests, as a last resort. The implementation of the strategy is intended to minimise the use of animals in the testing of acute systemic toxicity and toxicokinetics, whilst satisfying the scientific and logistical demands of the EU REACH 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.     

An unexpected challenge: ionizable compounds in the REACH chemical space

Purpose  

About 143,000 industrial chemicals have been pre-registered at the European Chemical Agency for registration according to REACH. The tools, models, and regressions employed for the chemical safety assessment of the registered compounds have limited applicability domains. Thus, it is an important question which fraction of the pre-registered compounds falls into these applicability domains.     

Testing and Risk Assessment of Persistent and Bioaccumulating Chemical Substances—Improvements within REACH?

In the proposed new European chemicals regulations—the REACH system—the improved control of persistent and bioaccumulating substances is stated as one of the tasks being of particular importance. In this article, the reliability and validity of the scientific basis for identification of persistent (P), bioaccumulating (B), and toxic (T) substances, and for assessing the risks that these substances may pose, are discussed. We have used the European Union risk assessment of pentabromodiphenyl ether, PentaBDE (CAS 32534-81-9) as a study case in the analysis. It is concluded that for PBT substances there is room for development both with regard to test methodology and with regard to risk assessment procedures.     

A critical evaluation of the 2011 ECHA reports on compliance with the REACH and CLP regulations and on the use of alternatives to testing on animals for compliance with the REACH regulation

On 30 June 2011, the European Chemicals Agency published two reports, one on the functioning of the REACH system, the other on the use of alternatives to animal testing in compliance with that system. The data presented are based on information gained during the first registration period under the REACH system, which included high production volume chemicals and substances of very high concern, which have the most extensive information requirements. A total of 25,460 registration dossiers were received, covering 3,400 existing, so-called 'phase-in', substances, and 900 new, so-called 'non-phase-in', substances. Data sharing and the joint submission of data are reported to have worked successfully. In the registration dossiers for these substances, results from new animal tests were included for less than 1% of all the endpoints; testing proposals (required for 'higher-tier' information requirements) were submitted for 711 in vivo tests involving vertebrate animals. The registrants mainly used old, existing experimental data, or options for the adaptation (waiving) of information requirements, before collecting new information. For predicting substance toxicity, 'read-across' was the second most-used approach, followed by 'weight-of-evidence'. In vitro toxicity tests played a minor role, and were only used when the respective test methods had gained the status of regulatory acceptance. All in all, a successful start to the REACH programme was reported, particularly since, in contrast to most predictions, it did not contribute to a significant increase in toxicity testing in animals.     

In vitro tests within the REACH information strategies

Tonnage-based information requirements are specified in the proposal on the regulation on the Registration, Evaluation and Authorisation of Chemicals (REACH) in the European Union. The hazard assessment for toxic endpoints should be performed by using a tiered approach, i.e. as an information strategy (IS), starting with an evaluation of all of the data already available, including animal in vivo and in vitro data, and human evidence and case reports, as well as data from (Quantitative)-Structure Activity Relationships ([Q]SARs) or read-across, before any further testing is suggested. To contribute to the implementation of the REACH system, the Nordic countries launched two projects: 1) a review of currently used testing strategies, including a comparison with the REACH requirements; and 2) the development of detailed ISs for skin and eye irritation/corrosion. The review showed that the ISs and classification criteria for the selected endpoints are inconsistent in many cases. In the classification criteria, human data and in vivo test results are usually the prerequisites. Other types of information, such as data from in vitro studies, can sometimes be used, but usually as supportive evidence only. This differs from the REACH ISs, where QSARs, read-across and in vitro testing are important elements. In the other part of the project, an IS for skin and eye irritation/corrosion was proposed. The strategy was "tested" by using four high production volume (HPV) chemicals: hydrogen peroxide, methyl tertiary-butyl ether (MTBE), trivalent chromium, and diantimony trioxide, but only MTBE and trivalent chromium are dealt with in this paper. The "test" revealed that in vivo data, human case reports and physical-chemical data were available and could be used in the evaluation. Classification could be based on the proposed IS and the existing data in all cases, except for the eye irritation/corrosion of trivalent chromium. Weight-of-evidence analysis appeared to be a useful step in the ISs proposed, and including it in the REACH strategies should be considered. For these chemicals, few in vitro and (Q)SAR data were available--more of these data would be generated, if the relevant guidance and legislation on classification were updated.     

Integrated decision-tree testing strategies for developmental and reproductive toxicity with respect to the requirements of the EU REACH legislation

Liverpool John Moores University and FRAME conducted a research project, sponsored by Defra, on the status of alternatives to animal testing with regard to the European Union REACH (Registration, Evaluation and Authorisation of Chemicals) system for the safety testing and risk assessment of chemicals. The project covered all the main toxicity endpoints associated with the REACH system. This paper focuses on the prospects for the use of alternative methods (both in vitro and in silico) in developmental and reproductive toxicity testing. It considers many tests based on primary cells and cell lines, and the available expert systems and QSARs for developmental and reproductive toxicity, and also covers tests for endocrine disruption. Ways in which reduction and refinement measures can be used are also discussed, particularly the use of an enhanced one-generation reproductive study, which could potentially replace the two-generation study, and therefore considerably reduce the number of animals required in reproductive toxicity. Decision-tree style integrated testing strategies are also proposed for developmental and reproductive toxicity and for endocrine disruption, followed by a number of recommendations for the future facilitation of developmental and reproductive toxicity testing, with respect to human risk assessment.     

An integrated decision-tree testing strategy for repeat dose toxicity with respect to the requirements of the EU REACH legislation

This paper presents some results of a joint research project conducted by FRAME and Liverpool John Moores University, and sponsored by Defra, on the status of alternatives to animal testing with regard to the European Union REACH (Registration, Evaluation and Authorisation of Chemicals) system for the safety testing and risk assessment of chemicals. The project covered all the main toxicity endpoints associated with REACH. This paper focuses on the use of alternative (non-animal) methods (both in vitro and in silico) for repeat dose (sub-acute, sub-chronic and chronic) toxicity testing. It reviews the limited number of in silico and in vitro tests available for this endpoint, and outlines new technologies which could be used in the future, e.g. the use of biomarkers and the 'omics' technologies. An integrated testing strategy is proposed, which makes use of as much non-animal data as possible, before any essential in vivo studies are performed. Although none of the non-animal tests are currently undergoing validation, their results could help to reduce the number of animals required for testing for repeat dose toxicity.     

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.