Standard information requirements
Standard information requirements
To meet your registration obligations, you must fulfil the minimum standard information requirements set by REACH. These requirements depend on the volume of the substance you manufacture or import into the EU/EEA.
- Follow the general information requirements for all registrants, including those that cover your substance identification, which are described in Annex VI to REACH.
- Follow the specific hazard information requirements relevant for the different tonnage bands outlined in Annexes VII-X to REACH. Note that the higher the volume, the more information that is required.
- In some cases, you may need information relevant for higher tonnages than your registered tonnage band to ensure the safe use of your substance, for example, if it has mutagenic properties.
- Perform all new tests for physicochemical hazards according to the methods referred to in the CLP Regulation, and in compliance with a recognised quality system or by laboratories complying with a relevant recognised standard. This ensures that the results are adequate for classification and labelling under CLP and follow the United Nations Recommendations on the Transport of Dangerous Goods, Manual of Tests and Criteria.
- Some physicochemical properties are interlinked with other information requirements. Make sure that information included in different parts of your dossier is consistent and explain any unexpected findings.
- REACH annexes are sequential. Annex VII requirements (e.g. for in vitro irritation testing) should be fulfilled before considering Annex VIII requirements (e.g. in vivo testing). There are some cases where you may perform an Annex VIII test to also fulfil an Annex VII requirement. For example, if your substance does not exert toxic effects, you can first perform the 28-day repeated-dose toxicity (Annex VIII) study and use the results within a weight-of-evidence approach to fulfil the acute oral toxicity endpoint (Annex VII).
- If you need new data for skin and eye irritation, or for skin sensitisation, you must always start with in vitro tests, regardless of the annual tonnage of the substance.
- If you need to fulfil REACH Annex VIII 8.4.2 requirements, you must perform an in vitro micronucleus study (OECD TG 487) and must include two positive control substances (i.e. one known clastogen and one known aneugen). If the substance induces an increase in the frequency of micronuclei, you must perform a second scoring using a centromere staining technique to identify the chromosomal aberration mode(s) of action (i.e. clastogenicity and/or aneugenicity). This is necessary to ensure hazard assessment to the extent permitted within the OECD test guideline, in particular, to avoid missing aneugenicity.
- If you get a positive result in any of the in vitro experiments (Annex VII 8.4.1 or Annex VIII 8.4.2 or 8.4.3), you must follow it up with an in vivo study. You must submit a testing proposal before mutagenicity testing on vertebrate animals can start. If you do not consider an in vivo follow-up test to be necessary, you must provide a scientifically sound and well-documented adaptation, as per Annex XI general rules for adaptation, with an appropriate justification in your dossier.
- You need to perform a study combining an in vivo comet assay (OECD Test Guideline 489) and an in vivo micronucleus test (OECD TG 474) if:
- a concern for chromosomal aberration exists or has been identified in vitro, associated or not with a concern for gene mutation; and
- there is no other adequate and appropriate in vivo genotoxicity data available.
The combination reduces the number of tests and the number of animals used, as it increases the possibility of detecting genotoxic substances within the same study, while ensuring information on the potential of the substance to induce chromosomal aberrations and/or gene mutations in vivo.
There may be substance-specific reasons that could justify deviating from this general approach, e.g.:
- If there is clear evidence that the substance and/or its metabolites will not be systemically available and won’t reach the bone marrow, then an in vivo micronucleus test (OECD TG 474) is not suitable.
- For substances showing only aneugenic properties, an in vivo micronucleus test (OECD TG 474) should be performed instead of the combined study, as the comet assay is not suitable to detect aneugens.
- When performing an in vivo micronucleus test, either in isolation or in combination with an in vivo comet assay, you must include:
- A second scoring using a centromere staining technique if the substance induces an increase in the frequency of micronuclei (OECD TG 474) and the chromosomal aberration mode of action of the substance is unknown;
- An appropriate investigation of target tissue exposure. This can be achieved by taking blood samples at appropriate times and measuring plasma levels of the substance and/or its metabolites if exposure cannot be demonstrated through other means, as described in the OECD TG 474. You need to demonstrate target tissue exposure to conclude that the micronucleus test is clearly negative.
- You may need to carry out a germ cell genotoxicity study (OECD TG 488 or OECD TG 483) for substances manufactured or imported at 100 tonnes per year or more (Annexes IX or X to REACH) if:
- an in vivo genotoxicity test on somatic cell is positive; and
- no clear conclusion can be made on germ cell mutagenicity.
- When carrying out an in vivo test for repeated dose toxicity, an appropriately high dose level should be used, in line with the corresponding OECD test guideline. Check ECHA’s advice on how to apply dose selection for repeated dose toxicity testing.
- A screening study (OECD TG 421 or OECD TG 422), required under Annex VIII, does not fulfil the information requirement for a sub-chronic toxicity study (90-days, OECD TG 408), nor for a pre-natal developmental toxicity study (OECD TG 414) or an extended one-generation reproductive toxicity study (OECD TG 443).
- To meet the standard information requirements for a substance registered for 1 000 tonnes or more per year (Annex X), you need to perform pre-natal developmental toxicity studies (OECD TG 414) on two species. According to OECD TG 414, rats are the preferred rodent species and rabbits are the preferred non-rodent species. If you consider another species to be more relevant, provide a justification.
- Have a look at ECHA’s technical report on how it identifies and concludes on the design of the extended one-generation reproductive toxicity study (EOGRTS). You will find crucial information sources for defining the EOGRTS design and triggering the study itself.
- When carrying out an in vivo test for reproductive toxicity, an appropriate high dose level should be used, in line with the corresponding OECD test guideline. Check ECHA’s advice on how to apply dose selection for reproductive toxicity testing.
- In biodegradation studies, make sure that the microbial inoculum is not adapted, as this is not accepted. Adaptation of microbial inoculum means that inoculum is in contact with the tested substance before initiating the biodegradation test. Aeration and washing with mineral media are not regarded as inoculum adaptation.
- Identify degradation products and report them accordingly. Information on degradation products is obtained from simulation and /or hydrolysis tests. Conduct additional testing for these products if they can pose a risk or are expected to be of otherwise high concern, e.g. persistent, bioaccumulative and toxic (PBT) or very persistent and very bioaccumulative (vPvB).
- Use the recommended test guidelines OECD TG 307, OECD TG 308 and OECD TG 309 for simulation testing for water, soil and sediment. Sewage treatment plant simulation tests (e.g. OECD TG 303 or OECD TG 314) are not appropriate as a sole source of information to conclude if a substance fulfils the persistent/very persistent criteria.
- When assessing persistency and bioaccumulation for PBT/vPvB assessment, you should also consider each constituent, impurity or additive present in a concentration at or above 0.1 % weight by weight (w/w) or, if not technically feasible, in concentrations as low as technically quantifiable. Also consider any relevant degradation/transformation products, i.e. at least those detected at ≥10 % of the applied dose at any sampling time or those that are continuously increasing during the study even if their concentrations do not exceed 10 % of the applied dose, as this may indicate persistence. Alternatively, justify why these are not relevant for the PBT/vPvB assessment.
- The formation of non-extractable residues (NERs) may be significant in the simulation tests in surface water, sediment and soil. By default, total NER is regarded as a non-degraded substance. If reasonably justified and analytically demonstrated, a certain part of NERs may be differentiated and quantified as irreversibly bound or as degraded to biogenic NERs. Such fractions could be regarded as removed when calculating the degradation half-lifes (ECHA Guidance R.126.96.36.199.3.). Quantify the NERs formed in the simulation tests in surface water, sediment and soil, and report results including a scientific justification of the used extraction procedures and solvents.
- Bioaccumulation in fish aqueous and dietary exposure (Method EU C.13 / OECD TG 305) is the preferred test for bioaccumulation. You must conduct a test for exposure via the aqueous route (OECD TG 305-I) unless it can be demonstrated that it is not technically possible. If you justify and document that testing through aquatic exposure is not technically possible, you may conduct a study using the dietary exposure route (OECD 305-III).
- Use the recommended fish early-life stage (FELS) toxicity test (OECD TG 210) to examine long-term fish toxicity. The test covers several life stages of the fish from the newly fertilised egg, through to its hatch and early stages of growth, and is appropriate for examining the potential toxic effects of substances expected to cause effects over a longer exposure period, or which require a longer time to reach a steady state.
- OECD TG 204 (Fish, Prolonged Toxicity Test: 14-day study) cannot be considered as a suitable long-term test. This study is regarded as a prolonged toxicity study with fish mortality as the examined major endpoint.
- The information on acute aquatic toxicity (required at REACH Annexes VII and VIII) is essential for aquatic classification under CLP and, more specifically, for deriving the M factor. CLP includes both acute and chronic hazard categories for the aquatic environment and you must assess both when addressing this hazard class.
- Chronic toxicity studies are used for aquatic chronic classification and are required for substances registered at 100-1000 tpa (REACH Annex IX). These tests are particularly important for poorly soluble substances which might not reach equilibrium in a short-term study. Therefore, the requirement for long-term studies is triggered already at REACH Annex VII (Daphnia) and Annex VIII (fish) for poorly soluble substances.
- Use the equilibrium partitioning method (EPM) to predict toxicity to terrestrial organisms only when effects are observed in the aquatic toxicity tests. If a substance does not show effects in the aquatic toxicity tests, this method cannot be used.
- The intrinsic properties of chemicals on soil microbial communities are not addressed through the EPM extrapolation method and the potential adaptation possibility outlined for the information requirement of Annex IX, Section 9.4. does not apply for the information requirement under Annex IX, section 9.4.2. The nitrogen transformation test (OECD TG 216) is considered sufficient to fulfil the information requirement of effects on soil micro-organisms (Annex IX, Section 9.4.2.) for most non-agrochemicals. For agrochemicals, OECD TG 217 is also needed.
- For substances that have a high potential to adsorb to soil or that are very persistent (with a Log Kow >5 or a DT50 >180 days or, in the absence of DT50 the substance is considered not readily biodegradable), you need to perform a long-term terrestrial toxicity test according to Annex X instead of carrying out short-term testing, even if the substance is registered under Annex IX (100-1 000 tonnes per year).
- Provide adequate information on the physicochemical and fate properties of the test material. If required, follow the specific requirements for substances that are difficult to test (OECD Guidance Document No.23 on Aqueous-phase Aquatic Toxicity Testing of Difficult Test Chemicals).
- For all aquatic studies, always provide a reliable analytical monitoring of exposure concentrations.
- For some substances, it may be difficult to achieve and maintain the desired exposure concentrations. You must monitor the test concentrations of your substance throughout the exposure duration and report the results. If it is not possible to demonstrate the stability of exposure concentrations, i.e. measured concentrations are not within 80-120 % of nominal concentrations, you must report the effect concentration based on measured values.
- For multi-constituent or UVCB substances that contain constituents with different properties, e.g. a wide range of water solubilities, use one of the appropriate techniques for aquatic toxicity testing described in the OECD Guidance Document No. 23.
- You may be required to perform longer term fish toxicity tests that go beyond those described in Annex IX, column 1. This is based on the Board of Appeal’s decision (A-011-2018) from 4 May 2020 stating that Chemical Safety Assessment specified under REACH Annex IX (Section 9.1, Column 2) does not allow registrants to omit information on long-term toxicity to fish under column 1. Instead, it must be understood as a trigger for providing further information on long-term aquatic toxicity if the chemical safety assessment according to Annex I indicates such a need. Further long-term fish toxicity tests than those described in Annex IX, Column 1, may be required depending on the properties of the substance.
- In situations where exposure is absent or so low that additional hazard information will not lead to improved risk management, you may use an exposure-based adaptation (Annex XI, Section 3; ECHA Guidance R.5). Remember to clearly define and justify the legal basis for such an adaptation, i.e. Annex XI, Section 3.2(a) and/or (b) and/or (c). Registrants must provide adequate justification and documentation based on a thorough and rigorous exposure assessment in accordance with Section 5 of Annex I to REACH and must meet the criteria specified for the type of exposure-based adaptation that is being claimed. All stages of the life cycle of the substance must be considered in the justification (including article service-life, if relevant, and the waste stage).
- Board of Appeal decision on case A-011-2018 overrides advice given in the ECHA Guidance. As a result, information on aquatic toxicity described in ECHA’s Guidance on Information Requirements and Chemical Safety Assessment is no longer valid, in relation to the use of the REACH Annex IX, section 9.1, Column 2 as a waiver for the information requirement under Column 1. Revised guidance is foreseen to be published in autumn 2023, describing that Chemical Safety Assessment is no longer a possibility to adapt the tests specified under Column 1.
- REACH Annex IX (Section 9.2, Column 2) does not allow you to omit information on degradation under Column 1. Instead, it is a trigger for giving more information on degradation if the chemical safety assessment according to Annex I indicates such a need. This means that the information on degradation described in ECHA’s Guidance on Information Requirements and Chemical Safety Assessment related to REACH Annex IX, Section 9.2, Column 2 as a waiver for information requirements under Column 1 is not applicable.
- Specific rules for adaptation listed under Column 2 of Annex IX, sections 188.8.131.52-4 and 9.2.3 and the general rules of Annex XI apply. You must clearly define and justify the legal basis for any adaptation and provide adequate justification and documentation supporting the applied adaptation. An adaptation according to Annex XI, Section 3.2(a) is not applicable for (potential or known) PBT/vPvB substances. This is because a “safe” concentration level in the environment cannot be established using the methods currently available with sufficient reliability for an acceptable risk to be determined quantitatively (Annex I, Section 4.0.1; ECHA Guidance R.11.1.).
- ECHA recommends to start testing with simulation in surface water (i.e. OECD TG 309) if technically feasible. Testing in soil or sediment could also be considered first on the basis of exposure considerations (e.g. direct releases expected to specific compartments) or when there is knowledge available about persistence of the substance in specific compartments and/or it reflects the worst case of the substance’s persistence potential.
- When the substance meets persistent or very persistent criteria (as per REACH Annex XIII) in one compartment (starting testing from the most relevant as described above), no further testing of other environmental compartments is normally necessary.
- In general, results of a single simulation degradation study cannot be directly extrapolated to other environmental compartments (Guidance R.11). So, if for the first tested compartment a conclusion of “not persistent” is made, further data generation in other compartments is necessary.
- For substances containing multiple constituents, impurities and/or additives the selection of the relevant test material (constituents/fractions of constituents/the whole substance) may have to be based on the principles and approaches described in ECHA Guidance R.11, Section R.184.108.40.206.
- For soil and sediment simulation degradation testing, a substance is considered to have a high potential for adsorption to soil or sediment if:
- Log Koc ≥4;
- Log Kow ≥4 and/or ionisable (at pH 4-9) and/or surface active (default setting unless Log Koc <4 is demonstrated through an appropriate batch equilibrium test using relevant soil and/or sediment samples).