A New Approach for Reach
Alternative Methods - Compilation of dossiers that contain hazards and risks of chemicals have been required for previous chemical regulatory schemes, however, Reach brings a different perspective to acquiring data. Reach is not test prescriptive, instead requiring data gaps to be filled. Two main aims of Reach; to provide more information on chemical hazards and to reduce animal testing have, in the past, had the potential to be conflicting. To meet both these aspirations requires careful consideration of several factors.
Article 1 of Reach states that "The purpose of this Regulation is to ensure a high level of protection of human health and the environment, including the promotion of alternative methods for assessment of hazards of substances [...]". Consequently, this statement establishes the importance of these aspects throughout the whole regulation.
Reach endeavors to protect human health and the environment by decreasing the risks from chemicals. So that risks from chemicals can be decreased, using appropriate risk reduction measures, the hazards of chemicals must be established. Establishment of hazards of chemicals has previously relied heavily on information provided from in vivo animal tests. However, the aim of Reach to promote alternative methods for the assessment of hazards of substances significantly changes the emphasis from the elucidation of such hazards from animal tests to looking for alternative ways of obtaining such information.
Filling Of Data Gaps
Information requirements to obtain data on hazards of substances are outlined in Reach Annexes VII to X. Standard physicochemical, toxicological and ecotoxicological information requirements there are listed for each tonnage band. Beside the standard requirements there are specific corresponding rules, where the standard information may be omitted, replaced by other information, provided at a different stage or adapted in another way. In addition to the aforementioned adaptations, the standard information requirements may be adapted according to general rules outlined in Annex XI "General rules for adaptation of the standard testing regime set out in Annexes VII to X".
These adaptations provide for the filling of data gaps with alternative methods.
Using these adaptations, an integrated approach to hazard elucidation can be formulated. Reach Guidance is available from the European Chemicals Agency (ECHA) and should be consulted before embarking upon devising a strategy for filling information requirements necessary for registration under Reach.
An Integrated Testing Strategy (ITS) is a process for registrants of substances to determine what data may be required.
During the development of an ITS, generation of new information may be required. Alternative methods should primarily be considered for generating such data. Such alternatives can be used in a weight of evidence approach to satisfy the information requirements. The results of all methods should be adequate for the purpose of hazard (classification and labeling) or risk assessment.
In vitro studies are non-animal tests, usually using isolated cells on biological membranes. They are available for a number of information requirements and more are continuously being developed. Before use as an acceptable alternative method, in vitro studies should either be validated according to internationally agreed validation principles (such as the OECD procedures for the acceptance of test methods), or if not yet validated, they should be "suitable" (e.g., meet the requirements of European Centre for the Validation of Alternative Methods (ECVAM) for entry into pre-validation). There should also be adequate and reliable documentation of the method.
(Quantitative) Structure-Activity Relationship models (Q)SARs) provide information on the predicted hazards of a substance by examining of its structure and form and comparing it with known identifiers. (Q)SARs can be used to fill information requirements in Reach on a case-by-case basis, by either forming part of a weight of evidence approach, or as a full replacement. To be suitable for full replacement, (Q)SARs should have had their scientific validity established and the substance should be in the applicability domain of the model (e.g. a particular substance should be suitable for a particular model). Adequate and reliable documentation of the methods is also necessary, and ECHA have developed method and prediction reporting formats (QMRFs and QPRFs, respectively) to facilitate this.
A read-across and substance grouping approaches are also methods of filling information requirements. Similar substances may be grouped together, and intrinsic properties read-across to other members of the group. The robustness of a grouping approach will increase with increasing group members. Suitable justification is required to use such approaches.
Data may be waived according to the adaptations, for example, not testing a corrosive substance for repeated dose dermal toxicity because the necessary risk reduction measures are already in place. Requirements in Annexes VII to X may also be waived based on exposure scenarios. So called exposure-based waiving should be justified in line with the specific guidance developed.
By formulating an ITS and using a weight of evidence approach, information requirements in Reach can be filled using a variety of existing and emerging alternative methods. A large amount of guidance is available from ECHA on this subject.