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.

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.

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 9 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 would 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 (ECHA website).

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 at all tonnages. HSE would like to remind registrants 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 fully applicable 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), ECHA (Guidance on Information Requirements and Chemical Safety Assessment Chapter R.7a: Endpoint specific guidance available on the ECHA website) and McMillian et al. (2022)¹. Weight-of-evidence assessments should be conducted and documented in accordance with Annex 11 of UK REACH.

Recommendations for meeting environmental information requirements

Robust study summaries (RSS) for environmental studies

Registrants should include the following information in RSS to demonstrate information requirement endpoints are reliable:

• Information to demonstrate how test guideline validity criteria were met;
• Details of aquatic solvent concentrations and controls (if applicable);
• Adequate analytical method detail to confirm analytical measurements including information on limit of detection/quantification and test item identification and/or multi-constituent or UVCB substance constituent(s) if relevant;
• Justification for the choice of test item if this is different from the registered substance (for example if using a transformation product or a multi-constituent / UVCB substance constituent), noting that it might be useful to consult OECD’s Guidance Document on Aquatic Toxicity Testing of Difficult Substances and Mixtures (2019) available on the OECD website; and
• Endpoints based on measured concentrations where aquatic exposure concentrations were not stable (i.e., within 80 to 120% of nominal over the study period) unless otherwise justified.

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 available on the sciencedirect website.