Recommendations to registrants
General recommendations
Keep contact details up to date
Ensure the contact details for your company in the Comply with UK REACH service are kept up to date – in particular email addresses, since email is the primary method of communication between the Agency and registrants.
IUCLID validation assistant
Use the IUCLID validation assistant to check that you have entered the required information for the relevant tonnage band in the correct sections of IUCLID.
Adaptations to standard testing
If you want to adapt standard testing or replace the experimental value with a prediction, you need to provide the legal basis for the adaptation and the information used to fulfil the information requirement, e.g., a justification document and relevant studies or documentation to support the prediction.
Minimising new tests on vertebrate animals
Registrants are reminded that, in accordance with Article 25 and Annex 6 to UK REACH, testing on vertebrate animals for the purposes of the Regulation shall be undertaken only as a last resort. As such, registrants should consider alternative methods where applicable. They must also take measures to prevent duplication of vertebrate tests that have been conducted in other jurisdictions or for other regulatory purposes.
In line with Article 12 of UK REACH, registrants should include all relevant toxicological and ecotoxicological information that is available to them. This could include non-standard data and/or adaptations to the standard testing regime in accordance with Annex 11 to UK REACH to inform on (eco)toxicity endpoints.
New guidance is available advising how registrants can minimise testing on vertebrates when meeting the information requirements of UK REACH.
The Q(SAR) Assessment Framework is now available
(Quantitative) structure-activity relationship or (Q)SAR models are computer-based tools designed to predict properties of a substance based on its chemical structure. The OECD (Q)SAR Assessment Framework (oecd.org) should be consulted by registrants seeking to use these models to help meet information requirements in registrations.
It is important that the correct documentation is submitted in support of a (Q)SAR. The OECD-recommended documentation comprises:
- (Q)SAR model reporting format (QMRF) to document the model (usually available from the model developer)
- (Q)SAR prediction reporting format (QPRF) to document the prediction (prediction-specific, provided by the (Q)SAR user)
The latest versions of the QMRF and QPRF are included in the (Q)SAR assessment framework (oecd.org).
Additional guidance (europa.eu) on the use and reporting of (Q)SARs is also available.
Robust study summaries (RSS) in registration dossiers for novel substances
Article 14(1), in conjunction with Annex 1 and Article 10(a)(vii) of UK REACH, requires the provision of RSS for information derived from the application of Annexes 7 to 10 for substances manufactured and/or imported at or above 10 tonnes per year. Annex 1 (1.1.4 & 3.1.5) describes the conditions under which RSS shall be prepared and submitted. Normally, the study or studies giving rise to the highest concern and that are used to derive conclusions in the chemical safety assessment shall be subject to RSS. However, HSE requests that RSS be provided for all studies, including those for substances manufactured and/or imported at less than 10 tonnes per year and for studies covering the physicochemical endpoints. This will facilitate any evaluation of the dossier conducted by HSE and make the task of updating the dossier more straightforward for the registrant should an increase in tonnage band be required in the future.
Guidance regarding the endpoint-specific information expected in RSS can be found in the ECHA Practical Guide 3: How to report robust study summaries on the ECHA website. This guidance remains valid for UK REACH when read in a GB context.
In addition, an OECD project led by ECHA has developed guidance on preparing RSS for individual Information requirements; this is available on the ECHA website.
Guidance on test items used in studies
The test material used to generate the new data must be selected taking into account the following:
- the variation in compositions reported by all members of a joint submission
- the boundary composition(s) of the substance
- the impact of each constituent/ impurity on the test results for the endpoint to be assessed. For example, if a constituent/impurity is known to have an impact on (eco)toxicity, the selected test material must contain that constituent or impurity
- if the composition of the test material deviates from that used in older studies in the dossier, suitable comparability should be clearly demonstrated
Registrants should include the following information in the dossier on the test material to demonstrate the relevance of the test item to the registered substance:
- the composition of the test material selected for each study, under the “Test material information” section, for each respective endpoint study record in IUCLID
- all constituents of each test material along with their concentration values, percentage details and other parameters relevant for the property to be tested. This information is needed to assess whether the test material is relevant for the registered substance and whether it is suitable for use by all members of the joint submission, if relevant. Technical instructions on how to report the above is available in the ECHA manual on How to prepare registration and PPORD dossiers on the ECHA website
- test item name and identifier e.g. CAS number or equivalent
- batch code or equivalent identifier
- purity details
- justification for the choice of test item if this is different from the registered substance (for example if using a transformation product, a multi-constituent substance or a substance of unknown or variable composition, complex reaction products and biological materials, i.e., UVCB)
Providing explanations for IUCLID attachments
Registrants should include a commentary in the RSS to explain what attachments represent when they are included in the IUCLID dossier.
Recommendations for meeting physicochemical information requirements
Some physicochemical properties are interlinked with other information requirements
Registrants should ensure consistency when the same information is included in different parts of a dossier. An explanation should be provided detailing any unexpected findings.
Recommendations for meeting toxicological information requirements
OECD Guideline 497: Defined Approaches on Skin Sensitisation can be used to meet UK REACH information requirements
Information that allows a conclusion on whether the substance is a skin sensitiser is generally required in registration dossiers for all tonnages. Registrants are reminded that the information should also enable them to conclude on the substance’s potential to produce significant sensitisation in humans (CLP Category 1A).
OECD Guideline 497 on Defined Approaches on Skin Sensitisation (DASS; current version published in July 2023) defines a combination of non-animal test methods (which form the standard information requirement for this endpoint in Annex 7) and computational tools to predict both skin sensitisation hazard and potency.
The kinetic Direct Peptide Reactivity Assay (kDPRA) is one of the methods described in OECD test guideline (TG) 442C. Although it is not included in the DASS, it can be used to identify strong skin sensitisers (CLP Category 1A). However, it cannot distinguish between other skin sensitisers (CLP Category 1B) and non-sensitisers.
OECD Guideline 497 on Defined Approaches on Skin Sensitisation and OECD TG 442C are available on the OECD website.
The Direct Peptide Reactivity Assay (DPRA) is now applicable to UVCBs
The Annex 7 information requirement for skin sensitisation lists three key events that should be addressed in registration dossiers. The protein reactivity (key event 1) of substances of unknown or variable composition, complex reaction products and biological materials (UVCBs) can now be investigated in the DPRA (OECD TG 442C), which was updated in July 2023. The guideline now includes a gravimetric method that allows its use for UVCB substances.
The updated guideline is available on the OECD website.
Recommendations on the use of weight-of-evidence assessments for meeting the Annex 7 skin sensitisation information requirement
Where application of the DASS is not applicable fully to a substance and so cannot be used to reach a conclusion on its skin sensitisation hazard and/or potency, a weight-of-evidence approach might be possible. This approach can avoid the use of an animal test to meet the information requirement. Evidence that can be combined in a weight-of-evidence approach includes knowledge of the substance, read across and/or computational predictions for the substance or individual components of a UVCB, protein reactivity and existing animal data. Guidance on how to carry out a weight-of-evidence approach for skin sensitisation to fulfil information requirements is available from the OECD (OECD Guideline 497 on Defined Approaches on Skin Sensitisation available via the OECD website), ECHA (Guidance on Information Requirements and Chemical Safety Assessment Chapter R.7a: Endpoint specific guidance available on the ECHA website and McMillan et al. (2022)1. Weight-of-evidence assessments should be conducted and documented in accordance with Annex 11 of UK REACH.
Meeting the information requirement for serious eye damage/eye irritation
The in vitro method described in OECD TG 492B (Reconstructed Human Cornea-like Epithelium (RHCE) Test Method for Eye Hazard Identification, June 2024) provides a full replacement of the Draize acute eye irritation test in animals. Registrants should use this test to identify chemicals not requiring classification, those that should be classified for eye irritation (CLP Category 2) and those that should be classified for serious eye damage (CLP Category 1).
The guideline is available on the OECD website.
Recommendations for meeting ecotoxicological information requirements
Robust study summaries (RSS)
To demonstrate that information requirement endpoints are reliable, the RSS should include the following:
- information to demonstrate how test guideline validity criteria were met
- details of solvent concentrations and solvent controls, or state if this information is not available (if applicable)
- adequate method detail to confirm analytical measurements, including information on limits of detection/quantification and, test item identification and/or multi-constituent or UVCB substance constituent(s) where appropriate
- endpoints based on measured rather than nominal concentrations where aquatic exposure concentrations were not stable (such as within 80 to 120% of nominal over the study period) unless otherwise justified
- where analytical measurements reflect a limited number of test item components, or a surrogate substance, justification should be provided to support relevance to the overall test items concentrations
- justification as to why the highest test concentration represents the maximum achievable solubility in the test medium for poorly soluble substances
- justification regarding test item choice where the substance undergoes rapid transformation and hence the choice of test item is informed by the fate and potential (eco)toxicity of the degradants/transformation products. Guidance is available on the OECD website (Guidance Document on Aquatic Toxicity Testing of Difficult Substances and Mixtures)
The ECHA Practical Guide 3: How to report robust study summaries outlines what to include in an RSS and is available on the ECHA website.
Footnotes
1 McMillan D.S., Chilton M. L., Gao Y., Kern P.S., Schneider S.N. (2022). How to resolve inconclusive prediction from defined approaches for skin sensitisation in OECD Guideline No. 497. Regulatory Toxicology and Pharmacology, 135, 105248