(Q)SARs and REACH

REACH

 

In general, (Q)SARs can be used to provide the following types of information which may be useful for regulatory purposes:

  1. physicochemical properties
  2. toxic potential and potency
  3. environmental distribution and fate
  4. biokinetic processes
The main regulatory goals of REACH are:
  1. hazard and risk assessment
  2. classification and labelling
  3. the assessment of Persistent, Bioaccumulative and Toxic (PBT) substances and very persistent and very Bioaccumulative (vPvB) substances
For the regulatory purposes of REACH, (Q)SARs can in principle be applied in one or more of the following ways:
  1. provide information for use in priority setting procedures
  2. guide the experimental design of an experimental test or testing strategy
  3. improve the evaluation of existing test data
  4. provide mechanistic information (which could be used, for example, to support the grouping of chemicals into categories)
  5. fill a data gap needed for hazard and risk assessment
  6. fill a data gap needed for classification and labelling
  7. fill a data gap needed for PBT or vPvB assessment

 

Use of (Q)SARs instead of (animal) testing

To address financial and animal welfare concerns, REACH explicitly expresses the need to use (Q)SARs to reduce the extent of experimental testing. Article 25(1) of REACH specifies that "in order to avoid animal testing, testing on vertebrate animals for the purposes of this Regulation shall be undertaken only as a last resort." Article 12(1) provides that all information on physicochemical, toxicological and ecotoxicological properties of a substance that is relevant and available shall be included in the registration. This includes information generated by (Q)SARs and chemical grouping methods. The basic rules for generating information, whether by testing, (Q)SARs or other means, are laid down in Article 13(1), which states that:
    "Information on intrinsic properties of substances may be generated by means other than tests, provided that the conditions set out in Annex XI are met. In particular for human toxicity, information shall be generated whenever possible by means other than vertebrate animal tests, through the use of alternative methods, for example, in vitro methods or qualitative or quantitative structure-activity relationship models or from information from structurally related substances (grouping or read-across)..."
Annex XI provides a broad legislative framework for fulfilling the information requirements while limiting vertebrate testing to the extent possible. It foresees the use of (Q)SARs and grouping methods when "testing does not appear necessary" because the same level of information can be obtained by means other than (vertebrate) testing.
Regarding the use of (Q)SARs, Annex XI emphasises the principle that information generated by (Q)SARs may be used to indicate the presence or absenceof a certain dangerous property instead of experimental data, provided that the following conditions are met:
  1. results are derived from a (Q)SAR model whose scientific validity has been established
  2. the substance falls within the applicability domain of the (Q)SAR model
  3. results are adequate for the purpose of classification and labelling and/or risk assessment
  4. adequate and reliable documentation of the applied method is provided
In the ideal situation, (Q)SAR results can be used on their own for regulatory purposes. This requires that all of the above-mentioned conditions are fulfilled, as illustated in the following figure.
qsarchar03.png
The interrelated concepts of (Q)SAR validity, reliability, applicability and adequacy
In practice, however, there may be uncertainty in the fulfilment of one or more of the above-mentioned conditions. However, this does not preclude the use of the (Q)SAR estimate in the context of a weight-of-evidence approach, in which additional (particularly, experimental) information may compensate for uncertainties resulting from a lack of information on the (Q)SAR. The application of (Q)SARs can therefore reduce the amount of testing that would otherwise be necessary and can even replace the need for testing altogether.
The conditions for using (Q)SAR results refer explicitly to the need for scientific validation of the model. This does not imply that the model must have been officially validated by any given validation body or organisation, but it does mean that the registrant should justify the use of a given model and estimate used by providing adequate documentation. Specifically, the model must be characterised in accordance with the OECD validation principles.
The appropriate means of documenting (Q)SARs, having followed the OECD validation principles, are the (Q)SAR Model Reporting Format (QMRF) and the QSAR Prediction Reporting Format (QPRF). The QMRF provides information on the validation characteristics of the model, whereas the QPRF provides supplementary information on the applicability of the model to a given chemical. The Member State authorities will consider the adequacy of (Q)SAR predictions on a case-by-case basis, taking into account the validity and applicability of the model, as documented in the QMRF and QPRF, respectively. Thus, the acceptance of a particular (Q)SAR model and estimate under REACH comprises of initial acceptance by the Industry registrant and the subsequent acceptance by the authorities. REACH does not foresee any official adoption or certification process for (Q)SAR models. However, the Agency will provide guidance on assessing which models fulfil the above-mentioned conditions and will ptovide examples.
Further information on QSAR Reporting Formats can be found in the QSAR Database area.

 

REACH guidance on (Q)SARs

As part of the scientific and technical preparations for the implementation of REACH, an activity was set up to develop guidance on the applications of (Q)SARs. The REACH guidance on (Q)SARs is included in Chapter R.6 of the Guidance on Information Requirements and Chemical Safety Assessment. All of the finalised REACH guidance documents are available on the ECHA website: http://guidance.echa.europa.eu/guidance_en.htm.
ECHA has also published a practical guide on how to report (Q)SARs: http://echa.europa.eu/doc/publications/practical_guides/pg_report_qsars.pdf.
More information on the use of (Q)SARs in a regulatory context can be found in the Document area.