Adaptations

An adaptation to a standard information requirement means that instead of performing a test, you provide a justification. Your justification has to either be based on general rules as explained in Annex XI to REACH, or on specific rules for each information requirement as detailed in Column 2 of Annexes VII to X.

 

To adapt information requirements:
  • Follow and apply the general and specific rules for adaptations under REACH.
  • Refer to the appropriate rules and state your justification clearly.

 

Justify and document your adaptation properly
  • Information provided using an adaptation must be as reliable as if it was generated using the test required to fulfil the information requirement .
  • Make sure that the results of your adaptation are adequate for classification and labelling and for risk assessment. If they are not, ECHA will reject your adaptation.
  • Some adaptations can never be accepted. For example, ECHA is currently not aware of any in vitro methods or QSAR models that reliably predict higher-tier endpoints, including repeated-dose toxicity, carcinogenicity, developmental or reproductive toxicity studies.
  • You can only rely on data from computer models if you can ensure that the model is scientifically valid, your substance falls within the applicability domain of the model and the prediction is adequate for the regulatory endpoint in question. You need to provide the related documentation in your dossier for the data to be independently assessed. If you cannot, ECHA will reject your adaptation.
  • ECHA can only assess information provided in your registration dossier. This means that for each source of information you need an endpoint study record containing a study summary or a robust study summary. This also applies to calculated or predicted values.
  • If ECHA does not accept your adaptation, you will receive a decision. The decision explains why the adaptation was rejected and requests a standard test to be conducted and submitted by a given deadline .

 

Read-across approaches
  • You need to show that the substances are likely to be similar (eco)toxicologically:
  • Identify the group of substances clearly – describe their structural similarities and differences. Explain how structural differences may (or may not) impact the predicted properties of the substance.
  • To apply the read-across approach, you must understand and report the composition of your substance and the available test materials.
  • Provide detailed substance identity and analytical information.
  • For multi-constituent substances and those of unknown or variable composition, complex reaction products or of biological materials (UVCBs), you also need to explain the differences and similarities of the constituents between the target and source substances to establish structural similarity. This includes details on the composition of actual test materials used in studies with source substances. The impact of these differences on the prediction of hazardous properties needs to be explained as well .
  • If, for UVCBs, it is technically impossible or impractical to identify and quantify all constituents, you need to consider other techniques to estimate the quantitative and qualitative comparison of the compositions between the substances. Your read-across adaptation is more likely to be accepted if you can demonstrate you have made efforts to achieve this.
  • Provide a data matrix with all available physico-chemical and (eco)toxicological information.
  • A read-across adaptation can be accepted only if you provide a credible read-across hypothesis with a proper justification and reliable data for each endpoint.
  • If your hypothesis is based on similarity through (bio-) transformation, you need to provide data e.g. on toxicokinetics or metabolism.
  • If your hypothesis is based on structural similarity which leads to similar properties, you need to have reliable and relevant data on the lower-tier endpoints for both source and target substances to confirm your hypothesis and possibility to predict. This could be done by bridging data, for example, from Annex VII or VIII information requirements.
  • You need to provide comparable information for each endpoint: data on repeated dose toxicity does not necessarily support toxicity to reproduction or development. Read-across is usually endpoint-specific.
  • Explain the trends you use to support your prediction – including all inconsistencies and their impact on your prediction.
  • Use ECHA’s Read-Across Assessment Framework (RAAF) to validate that your read-across adaptation is robust and complete.
  • You can rely on data from structurally similar/analogue substances only if you have lawful access to the study reports and other relevant data generated with those substances.

 

Weight-of-evidence adaptations
  • You need documented justification on why the sources of information provide a conclusion on the information requirement under consideration:
  • In principle, any information can be part of a weight of evidence. The weight (contribution) of an individual source of information depends on its relevance to the endpoint in question and on its reliability.
    • Relevance is the extent to which the data and tests are appropriate, i.e. if the information is fully reliable, what contribution does it make to the overall conclusion on the information requirement being considered.
    • Reliability is the extent to which the information is correct, i.e. the inherent quality of the information. It is closely linked to the test method used to generate the data.
  • Read-across approaches can be used as part of a weight-of-evidence adaptation. You must demonstrate a reliable prediction from the source substance to show that the information is relevant. For this, a read-across justification is required and it must follow the principles of the RAAF.
  • (Q)SAR information can be used as part of a weight-of-evidence adaptation if it is adequately documented and the substance falls within the applicability of the used model.
  • A weight-of-evidence adaptation must consist of at least two relevant and reliable sources of information.
  • All weight-of-evidence adaptations are assessed and benchmarked against the information that would be normally be obtained from a study performed to meet this information requirement.
    • Completeness is the extent to which the available sources of information cover the data that would be obtained from the study that is normally performed for this information requirement, i.e. a comparison between key parameters covered by the sources of information and the key parameters covered by the benchmark test guideline.
  • The weight-of-evidence justification must address the relevance and reliability of each individual information source as well as completeness of the information.
  • ECHA can only assess information provided in your registration dossier. This means that for each source of information, you need an endpoint study record containing a study summary or robust study summary. This also applies to calculated or predicted values.

Consider if you can improve the rejected adaptation or provide a new valid adaptation addressing the deficiencies listed in ECHA’s decision. If you cannot do this by the given deadline , you must conduct the standard test as required in the decision.