Registration, Evaluation, Authorisation and Restriction of Chemicals

02006R1907-20191030 → 02006R1907-20200101

ANNEX I GENERAL PROVISIONS FOR ASSESSING SUBSTANCES AND PREPARING CHEMICAL SAFETY REPORTS 0. INTRODUCTION 0.1. The purpose of this Annex is to set out how manufacturers and importers are to assess and document that the risks arising from the substance they manufacture or import are adequately controlled during manufacture and their own use(s) and that others further down the supply chain can adequately control the risks. The chemical safety report shall also describe whether and which different nanoforms of substances as characterised in Annex VI are manufactured and imported, including an adequate justification for each information requirement describing when and how information on one form is used to demonstrate safety of other forms. The requirements speof the following hazard classes or categories setcific to nanoforms of a substance in this Annex apply to all nanoforms covered by the registration and without prejudice to requirements applicable to other forms of that substance. This Annex shall also apply adapted as necessary to producers and importers of articles required to make a chemical safety assessment as part of a registration. 0.2. The chemical safety assessment shall be prepared by one or more competent person(s) who have appropriate experience and received appropriate training, including refresher training. 0.3. The chemical safety assessment of a manufacturer shall address the manufacture of a substance and all the identified uses. The chemical safety assessment of an importer shall address all identified uses. The chemical safety assessment shall consider the use of the substance on its own (including any major impurities and additives), in a mixture and in an article, as defined by the identified uses. The assessment shall consider all stages of the life-cycle of the substance resulting from the manufacture and identified uses. The assessment shall address all nanoforms that are covered by the registration. The justifications and conclusions drawn from the assessment shall be relevant to these nanoforms. The chemical safety assessment shall be based on a comparison of the potential adverse effects of a substance with the known or reasonably foreseeable exposure of man and/or the environment to that substance taking into account implemented and recommended risk management measures and operational conditions. 0.4. Substances whose physicochemical, toxicological and ecotoxicological eco-toxicological properties are likely to be similar or follow a regular pattern as a result of structural similarity may be considered as a group, or category of substances. If the manufacturer or importer considers that the chemical safety assessment carried out for one substance is sufficient to assess and document that the risks arising from another substance or from a group or category of substances are adequately controlled then he can use that chemical safety assessment for the other substance or group or category of substances. The manufacturer or importer shall provide a justification for this. Where any of the substances exists in one or more nanoforms and data from one form are used in demonstration of the safe use of other forms, in accordance with the general rules set out in Annex XI, a scientific justification shall be given on how, applying the rules for grouping and read-across, the data from a specific test or other information (e.g. methods, results or conclusions) can be used for the other forms of the substance. Similar considerations apply to exposure scenarios and risk management measures. 0.5. The chemical safety assessment shall be based on the information on the substance contained in the technical dossier and on other available and relevant information. Manufacturers or importers submitting a proposal for testing in accordance with Annexes IX and X shall record this under the relevant heading of the chemical safety report. Available information from assessments carried out under other international and national programmes shall be included. Where available and appropriate, an assessment carried out under Community legislation (e.g. risk assessments completed under Regulation (EEC) No 793/93) shall be taken into account in the development of, and reflected in, the chemical safety report. Deviations from such assessments shall be justified. Thus the information to be considered includes information related to the hazards of the substance, the exposure arising from the manufacture or import, the identified uses of the substance, operational conditions and risk management measures applied or recommended to downstream users to be taken into account. In accordance with section 3 of Annex XI in some cases, it may not be necessary to generate missing information, because risk management measures and operational conditions which are necessary to control a well-characterised risk may also be sufficient to control other potential risks, which will not therefore need to be characterised precisely. If the manufacturer or importer considers that further information is necessary for producing his chemical safety report and that this information can only be obtained by performing tests in accordance with Annex IX or X, he shall submit a proposal for a testing strategy, explaining why he considers that additional information is necessary and record this in the chemical safety report under the appropriate heading. Where considered necessary, the proposal for a testing strategy may concern several studies addressing respectively different forms of the same substance for the same information requirement. While waiting for results of further testing, he shall record in his chemical safety report, and include in the exposure scenario developed, the interim risk management measures that he has put in place and those he recommends to downstream users intended to manage the risks being explored. The exposure scenarios and interim risk management measures recommended shall address all nanoforms that are covered by the registration. 0.6. Steps of a chemical safety assessment 0.6.1. A chemical safety assessment performed by a manufacturer or an importer for a substance shall include the following steps 1 to 4 in accordance with the respective sections of this Annex: 1. Human health hazard assessment. 2. Human health hazard assessment of physicochemical properties. 3. Environmental hazard assessment. 4. PBT and vPvB assessment. 0.6.2. In the cases referred to in point 0.6.3 the chemical safety assessment shall also include the following steps 5 and 6 in accordance with Sections 5 and 6 of this Annex: 5. Exposure assessment. 5.1. The generation of exposure scenario(s) (or the identification of relevant use and exposure categories, if appropriate). 5.2. Exposure estimation. 6. Risk characterisation. 0.6.3. Where as a result of steps 1 to 4 the manufacturer or importer concludes that the substance or, when applicable, nanoforms thereof fulfils the criteria for any of the following hazard classes or categories set out in Annex I to Regulation (EC) No 1272/2008 or is assessed to be a PBT or vPvB, the chemical safety assessment shall also include steps 5 … 474 unchanged words … the safety data sheet. 0.11. When assessing the risk of the use of one or more substances incorporated into a special mixture (for instance alloys), the way the constituent substances are bonded in the chemical matrix shall be taken into account. 0.11.bis When nanoforms are covered by the chemical safety assessment, an appropriate metric for the assessment and presentation of the results in steps 1-6 of the chemical safety assessment under 0.6.1 and 0.6.2 shall be considered, with the justification included in the chemical safety report and summarised in the safety data sheet. A multiple metric presentation, including mass metric information, is preferable. When possible, a method for reciprocal conversion shall be indicated. 0.12. Where the methodology described in this Annex is not appropriate, details of alternative methodology used shall be explained and justified in the chemical safety report. 0.13. Part A of the chemical safety report shall include a declaration that the risk management measures outlined in the relevant exposure scenarios for the manufacturer's or importer's own use(s) are implemented by the manufacturer or importer and that those exposure scenarios for the identified uses are communicated to distributors and downstream users in the safety data sheet(s). 1. HUMAN HEALTH HAZARD ASSESSMENT 1.0. Introduction 1.0.1. The objectives of the human health hazard assessment shall be to determine the classification of a substance in accordance with Regulation (EC) No 1272/2008; and to derive levels of exposure to the substance above which humans should not be exposed. This level of exposure is known as the Derived No-Effect Level (DNEL). 1.0.2. The human health hazard assessment shall consider the toxicokinetic profile (i.e. absorption, metabolism, distribution and elimination) of the substance and the following groups of effects: (1) acute effects such as acute toxicity, irritation and corrosivity; (2) sensitisation; (3) repeated dose toxicity; and (4) CMR effects (carcinogenity, germ cell mutagenicity and toxicity for reproduction). Based on all the available information, other effects shall be considered when necessary. 1.0.3. The hazard assessment shall comprise the following four steps: Step 1 Evaluation of non-human information. Step 2 Evaluation of human information. Step 3 Classification and Labelling. Step 4 Derivation of DNELs. The assessment shall address all nanoforms that are covered by the registration. 1.0.4. The first three steps shall be undertaken for every effect for which information is available and shall be recorded under the relevant section of the Chemical Safety Report and where required and in accordance with Article 31, summarised in … 538 unchanged words … and Articles 4 to 7 of Directive 1999/45/EC shall be presented and, if they are not included in Part 3 of Annex VI to Regulation (EC) No 1272/2008, justified. The assessment should always include a statement as to whether the substance or, when applicable, nanoforms thereof fulfils or does not fulfil the criteria given in Regulation (EC) No 1272/2008 for classification in the hazard class carcinogenicity category 1A or 1B, in the hazard class germ cell mutagenicity category 1A or 1B or in the hazard class reproductive toxicity category 1A or 1B. 1.3.2. If the information is inadequate to decide whether a substance or, when applicable, nanoforms thereof should be classified for a particular hazard class or category, the registrant registrants shall indicate and justify the action or decision he has taken as a result. 1.4. Step 4 Identification of DNEL(s) 1.4.1. Based on the outcomes of steps 1 and 2, (a) DNEL(s) shall be established for the substance, reflecting the likely route(s), duration and frequency of exposure. For some hazard classes, especially germ cell mutagenicity and carcinogenicity, the available information may not enable a toxicological threshold, and therefore a DNEL, to be established. If justified by the exposure scenario(s), a single DNEL may be sufficient. However, taking into account the available information and the exposure scenario(s) in Section 9 of the Chemical Safety Report it may be necessary to identify different DNELs for each relevant human population (e.g. workers, consumers and humans liable to exposure indirectly via the environment) and possibly for certain vulnerable sub-populations (e.g. children, pregnant women) and for different routes of exposure. A full justification shall be given specifying, inter alia, the choice of the information used, the route of exposure (oral, dermal, inhalation) and the duration and frequency of exposure to the substance for which the DNEL is valid. If more than one route of exposure is likely to occur, then a DNEL shall be established for each route of exposure and for the exposure from all routes combined. When establishing the DNEL, the following factors shall, inter alia, be taken into account: (a) the uncertainty arising, among other factors, from the variability in the experimental information and from intra- and inter-species variation; (b) the nature and severity of the effect; (c) the sensitivity of the human (sub-)population to which the quantitative and/or qualitative information on exposure applies. 1.4.2. If it is not possible to identify a DNEL, then this shall be clearly stated and fully justified. 2. PHYSICOCHEMICAL HAZARD ASSESSMENT 2.1. The objective of the hazard assessment for physicochemical properties shall be to determine the classification of a substance in accordance with Regulation (EC) No 1272/2008. 2.2. As a minimum, the potential effects to human health shall be assessed for the following physicochemical properties: explosivity, flammability, oxidising potential. If the information is inadequate to decide whether a substance or, when applicable, nanoforms thereof should be classified for a particular hazard class or category, the registrant shall indicate and justify the action or decision he has taken as a result. 2.3. The assessment of each effect shall be presented under the relevant heading of the Chemical Safety Report (Section 7) and where required and in accordance with Article 31, summarised in the Safety Data Sheet under headings 2 and 9. 2.4. For every physicochemical property, the assessment shall entail an evaluation of the inherent capacity of the substance to cause the effect resulting from the manufacture and identified uses. 2.5. The appropriate classification developed in accordance with the criteria in Regulation (EC) No 1272/2008 shall be presented and justified. 3. ENVIRONMENTAL HAZARD ASSESSMENT 3.0. Introduction 3.0.1. The objective of the environmental hazard assessment shall be to determine the classification of a substance in accordance with Regulation (EC) No 1272/2008 and to identify the concentration of the substance below which adverse effects in the environmental sphere of concern are not expected to occur. This concentration is known as the Predicted No-Effect Concentration (PNEC). 3.0.2. The environmental hazard assessment shall consider the potential effects on the environment, comprising the (1) aquatic (including sediment), (2) terrestrial and (3) atmospheric compartments, including the potential effects that may occur (4) via food-chain accumulation. In addition, the potential effects on the (5) microbiological activity of sewage treatment systems shall be considered. The assessment of the effects on each of these five environmental spheres shall be presented under the relevant heading of the Chemical Safety Report (Section 7) and where required and in accordance with Article 31, summarised in the Safety Data Sheet under headings 2 and 12. The assessment shall address all nanoforms that are covered by the registration. 3.0.3. For any environmental sphere, for which no effect information is available, the relevant section of the chemical safety report shall contain the sentence: This information is not available. The justification, including reference to any literature research carried out, shall … 433 unchanged words … shall be presented and justified. Any M-factor resulting from the application of Article 10 of Regulation (EC) No 1272/2008 shall be presented and, if it is not included in Part 3 of Annex VI to Regulation (EC) No 1272/2008, justified. The presentation and justification is applied to all nanoforms covered by the registration. 3.2.2. If the information is inadequate to decide whether a substance or, when applicable, nanoforms thereof should be classified for a particular hazard class or category, the registrant shall indicate and justify the action or decision he has taken as a result. 3.3. Step 3 Identification of the PNEC 3.3.1. Based on the available information, the PNEC for each environmental sphere shall be established. The PNEC may be calculated by applying an appropriate assessment factor to the effect values (e.g. LC50 or NOEC). An assessment factor expresses the difference between effects values derived for a limited number of species from laboratory tests and the PNEC for the environmental sphereIn general, the more extensive the data and the longer the duration of the tests, the smaller is the degree of uncertainty and the size of the assessment factor. An assessment factor of 1000 is typically applied to the lowest of three short term L(E)C50 values derived from species representing different trophic levels and a factor of 10 to the lowest of three long-term NOEC values derived from species representing different trophic levels.. 3.3.2. If it is not possible to derive the PNEC, then this shall be clearly stated and fully justified. 4. PBT AND VPVB ASSESSMENT 4.0. Introduction 4.0.1. The objective of the PBT and vPvB assessment shall be to determine if the substance fulfils the criteria given in Annex XIII and if so, to characterise the potential emissions of the substance. A hazard assessment in accordance with Sections 1 and 3 of this Annex addressing all the long-term effects and the estimation of the long-term exposure of humans and the environment as carried out in accordance with Section 5 (Exposure Assessment), step 2 (Exposure Estimation), cannot be carried out with sufficient reliability for substances satisfying the PBT and vPvB criteria in Annex XIII. Therefore, a separate PBT and vPvB assessment is required. 4.0.2. The PBT and vPvB assessment shall comprise the following two steps, which shall be clearly identified as such in Part B, Section 8 of the Chemical Safety Report: report. The assessment shall address all nanoforms that are covered by the registration: Step 1 : Comparison with the Criteria. Step 2 : Emission Characterisation. The assessment shall also be summarised in the Safety Data Sheet under heading 12. 4.1. Step 1: Comparison with the criteria This part of the PBT and vPvB assessment shall entail the comparison of the available information with the criteria given in Section 1 of Annex XIII and a statement of whether the substance fulfils or does not fulfil the criteria. The assessment shall be conducted in accordance with the provisions laid down in the introductory part of Annex XIII as well as Sections 2 and 3 of that Annex. 4.2. Step 2: Emission Characterisation If the substance fulfils the criteria or it is considered as if it is a PBT or vPvB in the registration dossier an emission characterisation shall be conducted comprising the relevant parts of the exposure assessment as described in Section 5. In particular it shall contain an estimation of the amounts of the substance released to the different environmental compartments during all activities carried out by the manufacturer or importer and all identified uses, and an identification of the likely routes by which humans and the environment are exposed to the substance. The estimation shall address all nanoforms that are covered by the registration. 5. EXPOSURE ASSESSMENT 5.0. Introduction The objective of the exposure assessment shall be to make a quantitative or and qualitative estimate of the dose/concentration of the substance to which humans and the environment are or may be exposed. The assessment shall consider all stages of the life-cycle of the substance resulting from the manufacture and identified uses and shall cover any exposures that may relate to the hazards identified in Sections 1 to 4. The assessment shall address all nanoforms that are covered by the registration. The exposure assessment shall entail the following two steps, which shall be clearly identified as such in the Chemical Safety Report: Step 1 Generation of exposure scenario(s) or the generation of relevant use and exposure categories. Step 2 Exposure Estimation. Where required and in accordance … 555 unchanged words … resulting from identified uses cover, where relevant, the service-life of articles and the waste stage. The emission estimation shall be performed under the assumption that the risk management measures and operational conditions described in the exposure scenario have been implemented. When nanoforms are covered by the registration, the emission estimation for these shall, where relevant, take account of situations when the conditions outlined in Annex XI section 3.2 point (c) are fulfilled. 5.2.3. A characterisation of possible degradation, transformation, or reaction processes processes, and an estimation of environmental distribution and fate shall be performed. When nanoforms are covered by the registration, a characterisation of the dissolution rate, the particle aggregation, the agglomeration and of the particle surface chemistry changes shall be included. 5.2.4. An estimation of the exposure levels shall be performed for all human populations (workers, consumers and humans liable to exposure indirectly via the environment) and environmental spheres for which exposure to the substance is known or reasonably foreseeable. Each … 787 unchanged words … humans via the environment 10.2.2. Environment 10.2.2.1. Aquatic compartment (including sediment) 10.2.2.2. Terrestrial compartment 10.2.2.3. Atmospheric compartment 10.2.2.4. Microbiological activity in sewage treatment systems (etc.) 10.x. Overall exposure (combined for all relevant emission/release sources) 10.x.1. Human health (combined for all exposure routes) 10.x.1.1. 10.x.2. Environment (combined for all emission sources) 10.x.2.1.

02006R1907-20191030 → 02006R1907-20200101

ANNEX III CRITERIA FOR SUBSTANCES REGISTERED IN QUANTITIES BETWEEN 1 AND 10 TONNES Criteria for substances and, when applicable, for nanoforms thereof, registered between 1 and 10 tonnes, with reference to Article 12(1)(a) and (b): (a) substances for which it is predicted (i.e. by the application of (Q)SARs or other evidence) that they are likely to meet the criteria for category 1A or 1B classification in the hazard classes carcinogenicity, germ cell mutagenicity or reproductive toxicity or the criteria in Annex XIII; (b) substances: (i) with dispersive or diffuse use(s) particularly where such substances are used in consumer mixtures or incorporated into consumer articles; and (ii) for which it is predicted (i.e. by application of (Q)SARs or other evidence) that they are likely to meet the classification criteria for any health or environmental hazard classes or differentiations under Regulation (EC) No 1272/2008. 1272/2008 or for substances with nanoforms, unless those nanoforms are soluble in biological and environmental media.

02006R1907-20191030 → 02006R1907-20200101

ANNEX VI INFORMATION REQUIREMENTS REFERRED TO IN ARTICLE 10 GUIDANCE NOTE ON FULFILLING THE REQUIREMENTS OF ANNEXES VI TO XI Annexes VI to XI specify the information that shall be submitted for registration and evaluation purposes according to Articles 10, 12, 13, 40, 41 and 46. For the lowest tonnage level, the standard requirements are in Annex VII, and every time a new tonnage level is reached, the requirements of the corresponding Annex have to be added. For each registration the precise information requirements will differ, according to tonnage, use use, and exposure. The Annexes shall thus be considered as a whole, and in conjunction with the overall requirements of registration, evaluation and the duty of care. A substance is defined in accordance with Article 3(1) and identified in accordance with section 2 in this Annex. A substance is always manufactured or imported in at least one form. A substance can also occur in more than one form. For all nanoforms covered by the registration certain specific information items shall be provided. Nanoforms shall be characterised as provided for in this Annex. The registrant shall justify why the information provided in the joint registration, covering the information requirements for the registered substances with nanoforms, is adequate for assessing the nanoforms. Information relevant to cover information requirements for such a substance can also be submitted separately by individual registrants, where justified in accordance with Article 11(3). More than one dataset may be required for one or more information requirements whenever there are significant differences in the properties relevant for the hazard, exposure and risk assessment and management of nanoforms. The information shall be reported in such a manner that it is clear which information in the joint submission pertains to which nanoform of the substance. Where technically and scientifically justified, the methodologies set out in Annex XI.1.5 shall be used within a registration dossier when two or more forms of a substance are grouped for the purposes of one, more or possibly all the information requirements. The requirements specific to nanoforms apply without prejudice to requirements applicable to other forms of a substance. Definition of a nanoform and a set of similar nanoforms: On the basis of the Commission Recommendation of 18 October 2011 on the definition of nanomaterialOJ L 275, 20.10.2011, p. 38., a nanoform is a form of a natural or manufactured substance containing particles, in an unbound state or as an aggregate or as an agglomerate and where, for 50 % or more of the particles in the number size distribution, one or more external dimensions is in the size range 1 nm-100 nm, including also by derogation fullerenes, graphene flakes and single wall carbon nanotubes with one or more external dimensions below 1 nm. For this purpose, particle means a minute piece of matter with defined physical boundaries; agglomerate means a collection of weakly bound particles or aggregates where the resulting external surface area is similar to the sum of the surface areas of the individual components and aggregate means a particle comprising of strongly bound or fused particles. A nanoform shall be characterised in accordance with section 2.4 below. A substance may have one or more different nanoforms, based on differences in the parameters in points 2.4.2 to 2.4.5. A set of similar nanoforms is a group of nanoforms characterised in accordance with section 2.4 where the clearly defined boundaries in the parameters in the points 2.4.2 to 2.4.5 of the individual nanoforms within the set still allow to conclude that the hazard assessment, exposure assessment and risk assessment of these nanoforms can be performed jointly. A justification shall be provided to demonstrate that a variation within these boundaries does not affect the hazard assessment, exposure assessment and risk assessment of the similar nanoforms in the set. A nanoform can only belong to one set of similar nanoforms The term nanoform, when it is referred to in the other Annexes, shall refer to a nanoform or a set of similar nanoforms, when one has been defined, as defined in this Annex. STEP 1 — GATHER AND SHARE EXISTING INFORMATION The registrant should gather all existing available test data on the substance to be registered, this would include a literature search for relevant information on the substance. Wherever practicable, registrations should be submitted jointly, in accordance with Articles 11 or 19. This will enable test data to be shared, thereby avoiding unnecessary testing and reducing costs. The registrant should also collect all other available and relevant information on the substance including on all nanoforms of the substance that are covered by the registration, regardless whether testing for a given endpoint is required or not at the specific tonnage level. This should include information from alternative sources (e.g. from (Q)SARs, read-across from other substances, in vivo and in vitro testing, epidemiological data) which may assist in identifying the presence or absence of hazardous properties of the substance and which can in certain cases replace the results of animal tests. In addition, information on exposure, use and risk management measures in accordance with Article article 10 and this Annex should be collected. Considering all this information together, the registrant will be able to determine the need to generate further information. STEP 2 — CONSIDER INFORMATION NEEDS The registrant shall identify what information is required for the registration. First, the relevant Annex or Annexes to be followed shall be identified, according to tonnage. These Annexes set out the standard information requirements, but shall be considered in conjunction with Annex XI, which allows variation from the standard approach, where it can be justified. In particular, information on exposure, use and risk management measures shall be considered at this stage in order to determine the information needs for the substance. STEP 3 — IDENTIFY INFORMATION GAPS The registrant shall then compare the information needs for the substance with the information already available and the extent to which currently available information can be applied to all nanoforms covered by the registration and identify where there are gaps. It is important at this stage to ensure that the available data is relevant and has sufficient quality to fulfil the requirements. STEP 4 — GENERATE NEW DATA/PROPOSE TESTING STRATEGY In some cases it will not be necessary to generate new data. However, where there is an information gap that needs to be filled, new data shall be generated (Annexes VII and VIII), or a testing strategy shall be proposed (Annexes IX and X), depending on the tonnage. New tests on vertebrates shall only be conducted or proposed as a last resort when all other data sources have been exhausted. The above approach shall also apply if there is a gap of available information for one or more nanoforms of the substance included in the jointly submitted registration dossier. In some cases, the rules set out in Annexes VII to XI may require certain tests to be undertaken earlier than or in addition to the standard requirements. NOTES Note 1: If it is not technically possible, or if it does not appear scientifically necessary to give information, the reasons shall be clearly stated, in accordance with the relevant provisions. Note 2: The registrant may wish to declare that certain information submitted in the registration dossier is commercially sensitive and its disclosure might harm him commercially. If this is the case, he shall list the items and provide a justification. INFORMATION REFERRED TO IN ARTICLE 10(a) (i) TO (v) 1. GENERAL REGISTRANT INFORMATION 1.1. Registrant 1.1.1. Name, address, telephone number, fax number and e-mail address 1.1.2. Contact person 1.1.3. Location of the registrant's production and own use site(s), as appropriate 1.2. Joint submission of data Articles 11 or 19 foresee that parts of the registration may be submitted by a lead registrant on behalf of other registrants. In this case, the lead registrant shall identify the other registrants specifying: their name, address, telephone number, fax number and e-mail address, parts of the present registration which apply to other registrants. Mention the number(s) given in this Annex or Annexes VII to X, as appropriate. Any other registrant shall identify the lead registrant submitting on his behalf specifying: his name, address, telephone number, fax number and e-mail address, parts of the registration which are submitted by the lead registrant. Mention the number(s) given in this Annex or Annexes VII to X, as appropriate. 1.3 Third party appointed under Article 4 1.3.1. Name, address, telephone number, fax number and e-mail address 1.3.2. Contact person 2. IDENTIFICATION OF THE SUBSTANCE For each substance, the information given in this section shall be sufficient to enable each substance to be identified. identified and the different nanoforms to be characterised. If it is not technically possible or if it does not appear scientifically necessary to give information on one or more of the items below, the reasons shall be clearly stated. 2.1. Name or other identifier of each substance 2.1.1. Name(s) in the IUPAC nomenclature or other international chemical name(s) 2.1.2. Other names (usual name, trade name, abbreviation) 2.1.3. EINECS or ELINCs number (if available and appropriate) 2.1.4. CAS name and CAS number (if available) 2.1.5. Other identity code (if available) 2.2. Information related to molecular and structural formula of each substance 2.2.1. Molecular and structural formula (including SMILES notation, if available) 2.2.2. Information on optical activity and typical ratio of (stereo) isomers (if applicable and appropriate) 2.2.3. Molecular weight or molecular weight range 2.3. Composition of each substance substance. Where a registration covers one or more nanoforms, these nanoforms shall be characterised pursuant to section 2.4 of this Annex. 2.3.1. Degree of purity ( %) (%) 2.3.2. Nature of impurities, including isomers and by-products 2.3.3. Percentage of (significant) main impurities 2.3.4. Nature and order of magnitude (… ppm, … %) of any additives (e.g. stabilising agents or inhibitors) 2.3.5. Spectral data (ultra-violet, (e.g. ultra-violet, infra-red, nuclear magnetic resonance or mass spectrum) 2.3.6. High-pressure liquid chromatogram, gas chromatogram 2.3.7. Description of the analytical methods or the appropriate bibliographical references for the identification of the substance and, where appropriate, for the identification of impurities and additives. This information shall be sufficient to allow the methods to be reproduced 2.4. Characterisation of nanoforms of a substance: For each of the characterisation parameters, the information provided may be applicable to either an individual nanoform or a set of similar nanoforms provided that the boundaries of the set are clearly specified. The information in points 2.4.2 – 2.4.5 shall be clearly assigned to the different nanoforms or sets of similar nanoforms identified in point 2.4.1 2.4.1. Names or other identifiers of the nanoforms or sets of similar nanoforms of the substance 2.4.2. Number based particle size distribution with indication of the number fraction of constituent particles in the size range within 1 nm – 100 nm 2.4.3. Description of surface functionalisation or treatment and identification of each agent including IUPAC name and CAS or EC number 2.4.4. Shape, aspect ratio and other morphological characterisation: crystallinity, information on assembly structure including e.g. shell like structures or hollow structures, if appropriate 2.4.5. Surface area (specific surface area by volume, specific surface area by mass or both) 2.4.6. Description of the analytical methods or the appropriate bibliographical references for the information elements in this sub-section. This information shall be sufficient to allow the methods to be reproduced. 3. INFORMATION ON MANUFACTURE AND USE(S) OF THE SUBSTANCE(S) Where a substance being registered is manufactured or imported in one or several nanoforms, the information on manufacture and use under 3.1-3.7 shall include separate information on the different nanoforms or sets of similar nanoforms as characterised in subsection 2.4. 3.1. Overall manufacture, quantities used for production of an article that is subject to registration, and/or imports in tonnes per registrant per year in: the calendar year of the registration (estimated quantity) 3.2. In the case of a manufacturer or producer of articles: brief description of the technological process used in manufacture or production of articles. Precise details of the process, particularly those of a commercially sensitive nature, are not required. 3.3. An indication of the tonnage used for his own use(s) 3.4. Form (substance, mixture or article) and/or physical state under which the substance is made available to downstream users. Concentration or concentration range of the substance in mixtures made available to downstream users and quantities of the substance in articles made available to downstream users. 3.5. Brief general description of the identified use(s) 3.6. Information on waste quantities and composition of waste resulting from manufacture of the substance, the use in articles and identified uses 3.7. Uses advised against (see Section 1 of the safety data sheet) Where applicable, an indication of the uses which the registrant advises against and why (i.e. non-statutory recommendations by supplier). This need not be an exhaustive list. 4. CLASSIFICATION AND LABELLING 4.1 The hazard classification of the substance(s), resulting from the application of Title I and II of Regulation (EC) No 1272/2008 for all hazard classes and categories in that Regulation, In addition, for each entry, the reasons why no classification is given for a hazard class or differentiation of a hazard class should be provided (i.e. if data are lacking, inconclusive, or conclusive but not sufficient for classification), 4.2 The resulting hazard label for the substance(s), resulting from the application of Title III of Regulation (EC) No 1272/2008, 4.3 Specific concentration limits, where applicable, resulting from the application of Article 10 of Regulation (EC) No 1272/2008. 5. GUIDANCE ON SAFE USE CONCERNING: This information shall be consistent with that in the Safety Data Sheet, Sheet where such a Safety Data Sheet is required according to Article 31. Where a substance being registered is also manufactured or imported in one or several nanoforms, the information pursuant to this Section shall address the different nanoforms or sets of similar nanoforms as characterised in subsection 2.4 where relevant. 5.1. First-aid measures (Safety Data Sheet heading 4) 5.2. Fire-fighting measures (Safety Data Sheet heading 5) 5.3. Accidental release measures (Safety Data Sheet heading 6) 5.4. Handling and storage (Safety Data Sheet heading 7) 5.5. Transport information (Safety Data Sheet heading 14) Where a Chemical Safety Report is not required, the following additional information is required: 5.6. Exposure controls/personal protection (Safety Data Sheet heading 8) 5.7. Stability and reactivity (Safety Data Sheet heading 10) 5.8. Disposal considerations 5.8.1. Disposal considerations (Safety Data Sheet heading 13) 5.8.2. Information on recycling and methods of disposal for industry 5.8.3. Information on recycling and methods of disposal for the public. 6. INFORMATION ON EXPOSURE FOR SUBSTANCES REGISTERED IN QUANTITIES BETWEEN 1 AND 10 TONNES PER YEAR PER MANUFATCURER OR IMPORTER Where a substance being registered is manufactured or imported in one or several nanoforms, the information pursuant to this Section shall address the different nanoforms or sets of similar nanoforms as characterised in subsection 2.4 separately. 6.1. Main use category: 6.1.1. (a) industrial use; and/or (b) professional use; and/or (c) consumer use. 6.1.2. Specification for industrial and professional use: (a) used in closed system; and/or (b) use resulting in inclusion into or onto matrix; and/or (c) non-dispersive use; and/or (d) dispersive use. 6.2. Significant route(s) of exposure: 6.2.1. Human exposure: (a) oral; and/or (b) dermal; and/or (c) inhalatory. 6.2.2. Environmental exposure: (a) water; and/or (b) air; and/or (c) solid waste; and/or (d) soil. 6.3. Pattern of exposure: (a) accidental/infrequent; and/or (b) occasional; and/or (c) continuous/frequent.

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ANNEX VII STANDARD INFORMATION REQUIREMENTS FOR SUBSTANCES MANUFACTURED OR IMPORTED IN QUANTITIES OF ONE TONNE OR MOREThis Annex shall apply to producers of articles that are required to register in accordance with Article 7 and to other downstream users that are required to carry out tests under this Regulation adapted as necessary. Column 1 of this Annex establishes the standard information required for: (a) non-phase-in substances manufactured or imported in quantities of 1 to 10 tonnes; (b) phase-in substances manufactured or imported in quantities of 1 to 10 tonnes and meeting the criteria in Annex III in accordance with Article 12(1)(a) and (b); and (c) substances manufactured or imported in quantities of 10 tonnes or more. Any other relevant physicochemical, toxicological and ecotoxicological information that is available shall be provided. For substances not meeting the criteria in Annex III only the physicochemical requirements as set out in section 7 of this Annex are required. Column 2 of this Annex lists specific rules according to which the required standard information may be omitted, replaced by other information, provided at a different stage or adapted in another way. If the conditions are met under which column 2 of this Annex allows adaptations, the registrant shall clearly state this fact and the reasons for each adaptation under the appropriate headings in the registration dossier. Without prejudice to the information submitted for other forms, any relevant physicochemical, toxicological and ecotoxicological information shall include characterisation of the nanoform tested and test conditions. A justification shall be provided where QSARs are used or evidence is obtained by means other than testing, as well as a description of the range of the characteristics/properties of the nanoforms to which the evidence can be applied. In addition to these specific rules, a registrant may adapt the required standard information set out in column 1 of this Annex according to the general rules contained in Annex XI with the exception of Section 3 on substance-tailored exposure … 409 unchanged words … if: based on structure, surface activity is expected or can be predicted, or surface activity is a desired property of the material. If the water solubility is below 1 mg/l at 20 °C the test does not need to be conducted. 7.7. Water solubility For nanoforms, in addition the testing of dissolution rate in water as well as in relevant biological and environmental media shall be considered. 7.7. The study does not need to be conducted if: the substance is hydrolytically unstable at pH 4, 7 and 9 (half-life less than 12 hours), or the substance is readily oxidisable in water. If the substance appears insoluble in water, a limit test up to the detection limit of the analytical method shall be performed. For nanoforms the potential confounding effect of dispersion shall be assessed when conducting the study. 7.8. Partition coefficient n-octanol/water 7.8. The study does not need to be conducted if the substance is inorganic. If the test cannot be performed (e.g. the substance decomposes, has a high surface activity, reacts violently during the performance of the test or does not dissolve in water or in octanol, or it is not possible to obtain a sufficiently pure substance), a calculated value for log P as well as details of the calculation method shall be provided. For nanoforms the potential confounding effect of dispersion in octanol and water shall be assessed when conducting the study. For nanoforms, whether of inorganic or organic substances, for which the partition coefficient n-octanol/water is not applicable the study of dispersion stability shall be considered instead. 7.9. Flash-point 7.9. The study does not need to be conducted if: the substance is inorganic, or the substance only contains volatile organic components with flash-points above 100 °C for aqueous solutions, or the estimated flash-point is above 200 °C, or the flash-point can … 444 unchanged words … potential of gases in a mixture with that of the oxidising potential of oxygen in air. 7.14. Granulometry 7.14. The study does not need to be conducted if the substance is marketed or used in a non solid or granular form. 7.14bis. Dustiness For nanoforms 7.14bis. The study does not need to be conducted if exposure to granular form of the substance during its life-cycle can be excluded. 8. TOXICOLOGICAL INFORMATION COLUMN 1 STANDARD INFORMATION REQUIRED COLUMN 2 SPECIFIC RULES FOR ADAPTATION FROM COLUMN 1 8.1. Skin corrosion/irritation 8.1. The study/ies do(es) not need to be conducted if: the substance is a strong acid (pH ≤ 2,0) or base (pH ≥ 11,5) and … 561 unchanged words … out in Article 13(3), first subparagraph, and Article 13(4) shall be considered appropriate to address this standard information requirement. 8.4. Mutagenicity 8.4. Further mutagenicity studies shall be considered in case of a positive result. 8.4.1. In vitro gene mutation study in bacteria 8.4.1. The study does not need to be conducted for nanoforms where it is not appropriate. In this case other studies involving one or more in vitro mutagenicity study(ies) in mammalian cells (Annex VIII, sections 8.4.2. and 8.4.3 or other internationally recognised in vitro methods) shall be provided. 8.5. Acute toxicity 8.5. The study/ies do(es) not generally need to be conducted if: the substance is classified as corrosive to the skin. 8.5.1. By oral route 8.5.1. The study need not be conducted if a study on acute toxicity by the inhalation route (8.5.2) is available. For nanoforms, a study by the oral route shall be replaced by a study by the inhalation route (8.5.2), unless exposure of humans via inhalation is unlikely, taking into account the possibility of exposure to aerosols, particles or droplets of an inhalable size. 9. ECOTOXICOLOGICAL INFORMATION COLUMN 1 STANDARD INFORMATION REQUIRED COLUMN 2 SPECIFIC RULES FOR ADAPTATION FROM COLUMN 1 9.1. Aquatic toxicity 9.1.1. Short-term toxicity testing on invertebrates (preferred species Daphnia) The registrant may consider long-term toxicity testing instead of short-term. 9.1.1. The study does not need to be conducted if: there are mitigating factors indicating that aquatic toxicity is unlikely to occur, occur for instance if the substance is highly insoluble in water or the substance is unlikely to cross biological membranes, or a long-term aquatic toxicity study on invertebrates is available, or adequate information for environmental classification and labelling is available. For nanoforms, the study may not be waived on the basis of high insolubility in water alone. The long-term aquatic toxicity study on Daphnia (Annex IX, section 9.1.5) 9.1.5.) shall be considered if the substance is poorly water soluble. soluble, or for nanoforms if they have low dissolution rate in the relevant test media. 9.1.2. Growth inhibition study aquatic plants (algae preferred) 9.1.2. The study does not need to be conducted if there are mitigating factors indicating that aquatic toxicity is unlikely to occur for instance if the substance is highly insoluble in water or the substance is unlikely to cross biological membranes. For nanoforms, the study may not be waived on the basis of high insolubility in water alone. 9.2. Degradation 9.2.1. Biotic 9.2.1.1. Ready biodegradability 9.2.1.1. The study does not need to be conducted if the substance is inorganic. Any other relevant physicochemical, toxicological and ecotoxicological information that is available shall be provided.

02006R1907-20191030 → 02006R1907-20200101

ANNEX VIII STANDARD INFORMATION REQUIREMENTS FOR SUBSTANCES MANUFACTURED OR IMPORTED IN QUANTITIES OF 10 TONNES OR MOREThis Annex shall apply to producers of articles that are required to register in accordance with Article 7 and to other downstream users that are required to carry out tests under this Regulation adapted as necessary. Column 1 of this Annex establishes the standard information required for all substances manufactured or imported in quantities of 10 tonnes or more in accordance with Article 12(1)(c). Accordingly, the information required in column 1 of this Annex is additional to that required in column 1 of Annex VII. Any other relevant physicochemical, toxicological and ecotoxicological information that is available shall be provided. Column 2 of this Annex lists specific rules according to which the required standard information may be omitted, replaced by other information, provided at a different stage or adapted in another way. If the conditions are met under which column 2 of this Annex allows adaptations, the registrant shall clearly state this fact and the reasons for each adaptation under the appropriate headings in the registration dossier. Without prejudice to the information submitted for other forms, any relevant physicochemical, toxicological and ecotoxicological information shall include characterisation of the nanoform tested and test conditions. A justification shall be provided where QSARs are used or evidence is obtained by means other than testing, as well as a description of the range of the characteristics/properties of the nanoforms to which the evidence can be applied. In addition to these specific rules, a registrant may adapt the required standard information set out in column 1 of this Annex according to the general rules contained in Annex XI. In this case as well, he shall clearly state the reasons for any decision to adapt the standard information under the appropriate headings in the registration dossier referring to the appropriate specific rule(s) in column 2 or in Annex XINote: conditions for not requiring a specific test that are set out in the appropriate test methods in the Commission Regulation on test methods as specified in Article 13(3) that are not repeated in column 2, also apply.. Before new tests are carried out to determine the properties listed in this Annex, all available in vitro data, in vivo data, historical human data, data from valid (Q)SARs and data from structurally related substances (read-across approach) shall be assessed first. In vivo testing with corrosive substances at concentration/dose levels causing corrosivity shall be avoided. Prior to testing, further guidance on testing strategies should be consulted in addition to this Annex. When, for certain endpoints, information is not provided for other reasons than those mentioned in column 2 of this Annex or in Annex XI, this fact and the reasons shall also be clearly stated. 7. INFORMATION ON THE PHYSICOCHEMICAL PROPERTIES OF THE SUBSTANCE 7.14ter. Further information on physicochemical properties Only for nanoforms Further testing for nanoforms covered by the registration shall be considered by the registrant or may be required by the Agency in accordance with Article 41, if there is an indication that specific additional particle properties significantly influence the hazard of or the exposure to those nanoforms. 8. TOXICOLOGICAL INFORMATION COLUMN 1 STANDARD INFORMATION REQUIRED COLUMN 2 SPECIFIC RULES FOR ADAPTATION FROM COLUMN 1 8.1. Skin corrosion/irritation 8.1. An in vivo study for skin corrosion/irritation shall be considered only if the in vitro studies under points 8.1.1 and 8.1.2 in Annex VII are not applicable, or the results of these studies are not adequate for classification and risk assessment. The study does not need to be conducted if: the substance is a strong acid (pH ≤ 2,0) or base (pH ≥ 11,5), or the substance is spontaneously flammable in air or in contact with water or moisture at room temperature, or the substance is classified as acute toxicity by the dermal route (Category 1), or an acute toxicity study by the dermal route does not indicate skin irritation up to the limit dose level (2000 mg/kg body weight). 8.2. Serious eye damage/eye irritation 8.2. An in vivo study for eye corrosion/irritation shall be considered only if the in vitro study(ies) under point 8.2.1 in Annex VII are not applicable, or the results obtained from these study(ies) are not adequate for classification and risk assessment. The study does not need to be conducted if: the substance is classified as skin corrosion, or the substance is a strong acid (pH ≤ 2,0) or base (pH ≥ 11,5), or the substance is spontaneously flammable in air or in contact with water or moisture at room temperature. 8.4. Mutagenicity 8.4.2. In vitro cytogenicity study in mammalian cells or in vitro micronucleus study 8.4.2. The study does not usually need to be conducted if adequate data from an in vivo cytogenicity test are available, or the substance is known to be carcinogenic category 1A or 1B or germ cell mutagenic category 1A, 1B or 2. 8.4.3. In vitro gene mutation study in mammalian cells, if a negative result in Annex VII, Section 8.4.1. and Annex VIII, Section 8.4.2. 8.4.3. The study does not usually need to be conducted if adequate data from a reliable in vivo mammalian gene mutation test are available. 8.4. Appropriate in vivo mutagenicity studies shall be considered in case of a positive result in any of the genotoxicity studies in Annex VII or VIII. 8.5. Acute toxicity 8.5. The study/ies do(es) not generally need to be conducted if: the substance is classified as skin corrosion. corrosive to the skin. In addition to the oral route (Annex VII, 8.5.1.), (8.5.1.) or to the inhalation route (8.5.2) for nanoforms, for substances other than gases, the information mentioned under 8.5.2 8.5.1. to 8.5.3 8.5.3. shall be provided for at least one other route. The choice for the second route will depend on the nature of the substance and the likely route of human exposure. If there is only one route of exposure, information for only that route needs to be provided. 8.5.2. By inhalation 8.5.2. Testing by the inhalation route is appropriate if exposure of humans via inhalation is likely taking into account the vapour pressure of the substance and/or the possibility of exposure to aerosols, particles or droplets of an inhalable size. 8.5.3. By dermal route 8.5.3. Testing by the dermal route is appropriate if: (1) inhalation of the substance is unlikely; and (2) skin contact in production and/or use is likely; and (3) the physicochemical and toxicological properties suggest potential for a significant rate of absorption through the skin. Testing by the dermal route does not need to be conducted if: the substance does not meet the criteria for classification as acute toxicity or STOT SE by the oral route and no systemic effects have been observed in in vivo studies with dermal exposure (e.g. skin irritation, skin sensitisation) or, in the absence of an in vivo study by the oral route, no systemic effects after dermal exposure are predicted on the basis of non-testing approaches (e.g. read across, QSAR studies). 8.6. Repeated dose toxicity 8.6.1. Short-term repeated dose toxicity study (28 days), one species, male and female, most appropriate route of administration, having regard to the likely route of human exposure. 8.6.1. The short-term toxicity study (28 days) does not need to be conducted if: a reliable sub-chronic (90 days) or chronic toxicity study is available, provided that an appropriate species, dosage, solvent and route of administration were used, or where a substance undergoes immediate disintegration and there are sufficient data on the cleavage products, or relevant human exposure can be excluded in accordance with Annex XI Section 3. The appropriate route shall be chosen on the following basis: Testing by the dermal route is appropriate if: (1) inhalation of the substance is unlikely; unlikely, and (2) skin contact in production and/or use is likely; likely, and (3) the physicochemical and toxicological properties suggest potential for a significant rate of absorption through the skin. Testing by the inhalation route is appropriate if exposure of humans via inhalation is likely taking into account the vapour pressure of the substance and/or the possibility of exposure to aerosols, particles or droplets of an inhalable size. For nanoforms toxicokinetics shall be considered including recovery period and, where relevant, lung clearance. The sub-chronic toxicity study (90 days) (Annex IX, Section 8.6.2) shall be proposed by the registrant if: the frequency and duration of human exposure indicates that a longer term study is appropriate; and one of the following conditions is met: other available data indicate that the substance may have a dangerous property that cannot be detected in a short-term toxicity study, or appropriately designed toxicokinetic studies reveal accumulation of the substance or its metabolites in certain tissues or organs which would possibly remain undetected in a short-term toxicity study but which are liable to result in adverse effects after prolonged exposure. Further studies shall be proposed by the registrant or may be required by the Agency in accordance with Article 40 or 41 in case of: failure to identify a NOAEL in the 28 or the 90 days study, unless the reason for the failure to identify a NOAEL is absence of adverse toxic effects, or toxicity of particular concern (e.g. serious/severe effects), or indications of an effect for which the available evidence is inadequate for toxicological and/or risk characterisation. In such cases it may also be more appropriate to perform specific toxicological studies that are designed to investigate these effects (e.g. immunotoxicity, neurotoxicity), neurotoxicity, and in particular for nanoforms indirect genotoxicity), or the route of exposure used in the initial repeated dose study was inappropriate in relation to the expected route of human exposure and route-to-route extrapolation cannot be made, or particular concern regarding exposure (e.g. use in consumer products leading to exposure levels which are close to the dose levels at which toxicity to humans may be expected), or effects shown in substances with a clear relationship in molecular structure with the substance being studied, were not detected in the 28 or the 90 days study. 8.7. Reproductive toxicity 8.7.1. Screening for reproductive/developmental toxicity, one species (OECD 421 or 422), if there is no evidence from available information on structurally related substances, from (Q)SAR estimates or from in vitro methods that the substance may be a developmental toxicant 8.7.1. This study does not need to be conducted if: the substance is known to be a genotoxic carcinogen and appropriate risk management measures are implemented, or the substance is known to be a germ cell mutagen and appropriate risk management measures are implemented, or relevant human exposure can be excluded in accordance with Annex XI section 3, or a pre-natal developmental toxicity study (Annex IX, 8.7.2) or, either an Extended One-Generation Reproductive Toxicity Study (B.56, OECD TG 443) (Annex IX, section 8.7.3) or a two-generation study (B.35, OECD TG 416), is available. If a substance is known to have an adverse effect on fertility, meeting the criteria for classification as toxic for reproduction category 1A or 1B: May damage fertility (H360F), and the available data are adequate to support a robust risk assessment, then no further testing for fertility will be necessary. However, testing for developmental toxicity must be considered. If a substance is known to cause developmental toxicity, meeting the criteria for classification as toxic for reproduction category 1A or 1B: May damage the unborn child (H360D), and the available data are adequate to support a robust risk assessment, then no further testing for developmental toxicity will be necessary. However, testing for effects on fertility must be considered. In cases where there are serious concerns about the potential for adverse effects on fertility or development, either an Extended One-Generation Reproductive Toxicity Study (Annex IX, section 8.7.3) or a pre-natal developmental toxicity study (Annex IX, section 8.7.2) may, as appropriate, be proposed by the registrant instead of the screening study. 8.8. Toxicokinetics 8.8.1. Assessment of the toxicokinetic behaviour of the substance to the extent that can be derived from the relevant available information. For nanoforms without high dissolution rate in biological media a toxicokinetics study shall be proposed by the registrant or may be required by the Agency in accordance with Article 40 or 41 in case such an assessment cannot be performed on the basis of relevant available information, including from the study conducted in accordance with 8.6.1. The choice of the study will depend on the remaining information gaps and the results of the chemical safety assessment. 9. ECOTOXICOLOGICAL INFORMATION COLUMN 1 STANDARD INFORMATION REQUIRED COLUMN 2 SPECIFIC RULES FOR ADAPTATION FROM COLUMN 1 9.1.3. Short-term toxicity testing on fish: the registrant may consider long-term toxicity testing instead of short-term. 9.1.3. The study does not need to be conducted if: there are mitigating factors indicating that aquatic toxicity is unlikely to occur, for instance if the substance is highly insoluble in water or the substance is unlikely to cross biological membranes, or a long-term aquatic toxicity study on fish is available. For nanoforms, the study may not be waived on the basis of high insolubility in water alone. Long-term aquatic toxicity testing as described in Annex IX shall be considered if the chemical safety assessment according to Annex I indicates the need to investigate further effects on aquatic organisms. The choice of the appropriate test(s) will depend on the results of the chemical safety assessment. The long-term aquatic toxicity study on fish (Annex IX, Section 9.1.6) shall be considered if the substance is poorly water soluble. soluble, or for nanoforms if they have low dissolution rate in the relevant test media. 9.1.4. Activated sludge respiration inhibition testing 9.1.4. The study does not need to be conducted if: there is no emission to a sewage treatment plant, or there are mitigating factors indicating that microbial toxicity is unlikely to occur, for instance the substance is highly insoluble in water, or the substance is found to be readily biodegradable and the applied test concentrations are in the range of concentrations that can be expected in the influent of a sewage treatment plant. For nanoforms, the study may not be waived on the basis of high insolubility in water alone. The study may be replaced by a nitrification inhibition test if available data show that the substance is likely to be an inhibitor of microbial growth or function, in particular nitrifying bacteria. 9.2. Degradation 9.2. Further degradation testing shall be considered if the chemical safety assessment according to Annex I indicates the need to investigate further the degradation of the substance. For nanoforms that are not soluble, nor have high dissolution rate, such test(s) shall consider morphological transformation (e.g. irreversible changes in particle size, shape and surface properties, loss of coating), chemical transformation (e.g. oxidation, reduction) and other abiotic degradation (e.g. photolysis). The choice of the appropriate test(s) will depend on the results of the chemical safety assessment. 9.2.2. Abiotic 9.2.2.1. Hydrolysis as a function of pH. 9.2.2.1. The study does not need to be conducted if: the substance is readily biodegradable, or the substance is highly insoluble in water. For nanoforms, the study may not be waived on the basis of high insolubility in water alone. 9.3. Fate and behaviour in the environment 9.3.1. Adsorption/desorption screening 9.3.1. The study does not need to be conducted if: based on the physicochemical properties the substance can be expected to have a low potential for adsorption (e.g. the substance has a low octanol water octanol-water partition coefficient), or the substance and its relevant degradation products decompose rapidly.For nanoforms, use of any physicochemical property (e.g. octanol-water partition coefficient) as a reason for waiving the study shall include adequate justification of its relevance to low potential for adsorption.

02006R1907-20191030 → 02006R1907-20200101

ANNEX IX STANDARD INFORMATION REQUIREMENTS FOR SUBSTANCES MANUFACTURED OR IMPORTED IN QUANTITIES OF 100 TONNES OR MOREThis Annex shall apply to producers of articles that are required to register in accordance with Article 7 and to other downstream users that are required to carry out tests under this Regulation adapted as necessary. At the level of this Annex, the registrant must submit a proposal and a time schedule for fulfilling the information requirements of this Annex in accordance with Article 12(1)(d). Column 1 of this Annex establishes the standard information required for all substances manufactured or imported in quantities of 100 tonnes or more in accordance with Article 12(1)(d). Accordingly, the information required in column 1 of this Annex is additional to that required in column 1 of Annexes VII and VIII. Any other relevant physicochemical, toxicological and ecotoxicological information that is available shall be provided. Column 2 of this Annex lists specific rules according to which the registrant may propose to omit the required standard information, replace it by other information, provide it at a later stage or adapt it in another way. If the conditions are met under which column 2 of this Annex allows an adaptation to be proposed, the registrant shall clearly state this fact and the reasons for proposing each adaptation under the appropriate headings in the registration dossier. Without prejudice to the information submitted for other forms, any relevant physicochemical, toxicological and ecotoxicological information shall include characterisation of the nanoform tested and test conditions. A justification shall be provided where QSARs are used or evidence is obtained by means other than testing, as well as a description of the range of the characteristics/properties of the nanoforms to which the evidence can be applied. In addition to these specific rules, a registrant may propose to adapt the required standard information set out in column 1 of this Annex according to the general rules contained in Annex XI. In this case as well, he shall … 705 unchanged words … recognised for structurally-related substances. Testing by the inhalation route is appropriate if: exposure of humans via inhalation is likely taking into account the vapour pressure of the substance and/or the possibility of exposure to aerosols, particles or droplets of an inhalable size. For nanoforms toxicokinetics shall be considered including recovery period and, where relevant, lung clearance. Further studies shall be proposed by the registrant or may be required by the Agency in accordance with Articles 40 or 41 in case of: failure to identify a NOAEL in the 90 days study unless the reason for the failure to identify a NOAEL is absence of adverse toxic effects, or toxicity of particular concern (e.g. serious/severe effects), or indications of an effect for which the available evidence is inadequate for toxicological and/or risk characterisation. In such cases it may also be more appropriate to perform specific toxicological studies that are designed to investigate these effects (e.g. immunotoxicity, neurotoxicity), neurotoxicity, and in particular for nanoforms indirect genotoxicity), or particular concern regarding exposure (e.g. use in consumer products leading to exposure levels which are close to the dose levels at which toxicity to humans may be expected). 8.7. Reproductive toxicity 8.7. The studies do not need to be conducted if: the … 963 unchanged words … include simulation testing in appropriate media (e.g. water, sediment or soil). 9.2.1. Biotic 9.2.1.2. Simulation testing on ultimate degradation in surface water 9.2.1.2. The study need not be conducted if: the substances is highly insoluble in water, or the substance is readily biodegradable. For nanoforms, the study may not be waived on the basis of high insolubility in water alone. 9.2.1.3. Soil simulation testing (for substances with a high potential for adsorption to soil) 9.2.1.3. The study need not be conducted: if the substance is readily biodegradable, or if direct and indirect exposure of soil is unlikely. 9.2.1.4. Sediment simulation testing (for substances with a high potential for adsorption to sediment) 9.2.1.4. The study need not be conducted: if the substance is readily biodegradable, or if direct and indirect exposure of sediment is unlikely. 9.2.3. Identification of degradation products 9.2.3. Unless the substance is readily biodegradable 9.3. Fate and behaviour in the environment 9.3.2. Bioaccumulation in aquatic species, preferably fish 9.3.2. The study need not be conducted if: the substance has a low potential for bioaccumulation (for instance a log Kow ≤ 3) and/or a low potential to cross biological membranes, or direct and indirect exposure of the aquatic compartment is unlikely. For nanoforms, use of any physicochemical property (e.g. octanol water partition coefficient, dissolution rate, dispersion stability) as a reason for waiving the study shall include adequate justification of its relevance to low potential for bioaccumulation or unlikely direct and indirect exposure of the aquatic compartment. 9.3.3. Further information on adsorption/desorption depending on the results of the study required in Annex VIII 9.3.3. The study need not be conducted if: based on the physicochemical properties properties, the substance can be expected to have a low potential for adsorption (e.g. the substance has a low octanol water partition coefficient), or the substance and its degradation products decompose rapidly. For nanoforms, use of any physicochemical property (e.g. octanol water partition coefficient, dissolution rate, dispersion stability) as a reason for waiving the study shall include adequate justification of its relevance to low potential for adsorption. 9.4. Effects on terrestrial organisms 9.4. These studies do not need to be conducted if direct and indirect exposure of the soil compartment is unlikely. In the absence of toxicity data for soil organisms, the equilibrium partitioning method may be applied to assess the hazard to soil organisms. Where the equilibrium partitioning method is applied to nanoforms, this shall be scientifically justified. The choice of the appropriate tests depends on the outcome of the chemical safety assessment. In particular for substances that have a high potential to adsorb to soil or that are very persistent, the registrant shall consider long-term toxicity testing instead of short-term. 9.4.1. Short-term toxicity to invertebrates 9.4.2. Effects on soil micro-organisms 9.4.3. Short-term toxicity to plants 10. METHODS OF DETECTION AND ANALYSIS Description of the analytical methods shall be provided on request, for the relevant compartments for which studies were performed using the analytical method concerned. If the analytical methods are not available this shall be justified.

02006R1907-20191030 → 02006R1907-20200101

ANNEX X STANDARD INFORMATION REQUIREMENTS FOR SUBSTANCES MANUFACTURED OR IMPORTED IN QUANTITIES OF 1000 TONNES OR MOREThis Annex shall apply to producers of articles that are required to register in accordance with Article 7 and to other downstream users that are required to carry out tests under this Regulation adapted as necessary. At the level of this Annex, the registrant must submit a proposal and a time schedule for fulfilling the information requirements of this Annex in accordance with Article 12(1)(e). Column 1 of this Annex establishes the standard information required for all substances manufactured or imported in quantities of 1000 tonnes or more in accordance with Article 12(1)(e). Accordingly, the information required in column 1 of this Annex is additional to that required in column 1 of Annexes VII, VIII and IX. Any other relevant physicochemical, toxicological and ecotoxicological information that is available shall be provided. Column 2 of this Annex lists specific rules according to which the registrant may propose to omit the required standard information, replace it by other information, provide it at a later stage or adapt it in another way. If the conditions are met under which column 2 of this Annex allows an adaptation to be proposed, the registrant shall clearly state this fact and the reasons for proposing each adaptation under the appropriate headings in the registration dossier. Without prejudice to the information submitted for other forms, any relevant physicochemical, toxicological and ecotoxicological information shall include characterisation of the nanoform tested and test conditions. A justification shall be provided where QSARs are used or evidence is obtained by means other than testing, as well as a description of the range of the characteristics/properties of the nanoforms to which the evidence can be applied. In addition to these specific rules, a registrant may propose to adapt the required standard information set out in column 1 of this Annex according to the general rules contained in Annex XI. In this case as well, he shall … 357 unchanged words … or effects shown in substances with a clear relationship in molecular structure with the substance being studied were not detected in the 28-day or 90-day study, or the substance may have a dangerous property that cannot be detected in a 90-day study. If nanoforms are covered by the registration, physicochemical characteristics, in particular particle size, shape and other morphological parameters, surface functionalisation and surface area, as well as molecular structure shall be taken into consideration when determining if one of the conditions above are met. 8.6.4. Further studies shall be proposed by the registrant or may be required by the Agency in accordance with Articles 40 or 41 in case of: toxicity of particular concern (e.g. serious/severe effects), or indications of an effect for which the available … 1,170 unchanged words … level. 10. METHODS OF DETECTION AND ANALYSIS Description of the analytical methods shall be provided on request, for the relevant compartments for which studies were performed using the analytical method concerned. If the analytical methods are not available this shall be justified.

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ANNEX XI GENERAL RULES FOR ADAPTATION OF THE STANDARD TESTING REGIME SET OUT IN ANNEXES VII TO X Annexes VII to X set out the information requirements for all substances manufactured or imported in quantities of: one tonne or more in accordance with Article 12(1)(a), 10 tonnes or more in accordance with Article 12(1)(c), 100 tonnes or more in accordance with Article 12(1)(d), and 1000 tonnes or more in accordance with Article 12(1)(e). In addition to the specific rules set out in column 2 of Annexes VII to X, a registrant may adapt the standard testing regime in accordance with the general rules set out in Section 1 of this Annex. Under dossier evaluation the Agency may assess these adaptations to the standard testing regime. The requirements specific to nanoforms in this Annex are without prejudice to requirements applicable to other forms of a substance. 1. TESTING DOES NOT APPEAR SCIENTIFICALLY NECESSARY 1.1. Use of existing data 1.1.1. Data on physical-chemical properties from experiments not carried out according to GLP or the test methods referred to in Article 13(3) Data shall be considered to be equivalent to data generated by the corresponding test methods referred to in Article 13(3) if the following conditions are met: (1) adequacy for the purpose of classification and labelling and/or risk assessment; (2) sufficient documentation is provided to assess the adequacy of the study; and (3) the data are valid for the endpoint being investigated and the study is performed using an acceptable level of quality assurance. 1.1.2. Data on human health and environmental properties from experiments not carried out according to GLP or the test methods referred to in Article 13(3) Data shall be considered to be equivalent to data generated by the corresponding test methods referred to in Article 13(3) if the following conditions are met: (1) adequacy for the purpose of classification and labelling and/or risk assessment; (2) adequate and reliable coverage of the key parameters foreseen to be investigated in the corresponding test methods referred to in Article 13(3); (3) exposure duration comparable to or longer than the corresponding test methods referred to in Article 13(3) if exposure duration is a relevant parameter; and (4) adequate and reliable documentation of the study is provided. 1.1.3. Historical human data Historical human data, such as epidemiological studies on exposed populations, accidental or occupational exposure data and clinical studies, shall be considered. The strength of the data for a specific human health effect depends, among other things, on the type of analysis and on the parameters covered and on the magnitude and specificity of the response and consequently the predictability of the effect. Criteria for assessing the adequacy of the data include: (1) the proper selection and characterisation of the exposed and control groups; (2) adequate characterisation of exposure; (3) sufficient length of follow-up for disease occurrence; (4) valid method for observing an effect; (5) proper consideration of bias and confounding factors; and (6) a reasonable statistical reliability to justify the conclusion. In all cases adequate and reliable documentation shall be provided. When nanoforms are covered by the registration the above approach shall address the nanoforms separately. 1.2. Weight of evidence There may be sufficient weight of evidence from several independent sources of information leading to the assumption/conclusion that a substance has or has not a particular dangerous property, while the information from each single source alone is regarded insufficient to support this notion. There may be sufficient weight of evidence from the use of newly developed test methods, not yet included in the test methods referred to in Article 13(3) or from an international test method recognised by the Commission or the Agency as being equivalent, leading to the conclusion that a substance has or has not a particular dangerous property. Where sufficient weight of evidence for the presence or absence of a particular dangerous property is available: further testing on vertebrate animals for that property shall be omitted, further testing not involving vertebrate animals may be omitted. In all cases adequate and reliable documentation shall be provided. When nanoforms are covered by the registration the above approach shall address the nanoforms separately. 1.3. Qualitative or Quantitative structure-activity relationship ((Q)SAR) Results obtained from valid qualitative or quantitative structure-activity relationship models ((Q)SARs) may indicate the presence or absence of a certain dangerous property. Results of (Q)SARs may be used instead of testing when the following conditions are met: results are derived from a (Q)SAR model whose scientific validity has been established, the substance falls within the applicability domain of the (Q)SAR model, results are adequate for the purpose of classification and labelling and/or risk assessment, and adequate and reliable documentation of the applied method is provided. The Agency in collaboration with the Commission, Member States and interested parties shall develop and provide guidance in assessing which (Q)SARs will meet these conditions and provide examples. When nanoforms are covered by the registration the above approach shall address the nanoforms separately. 1.4. In vitro methods Results obtained from suitable in vitro methods may indicate the presence of a certain dangerous property or may be important in relation to a mechanistic understanding, which may be important for the assessment. In this context, suitable means sufficiently well developed according to internationally agreed test development criteria (e.g. the European Centre for the Validation of Alternative Methods (ECVAM)) criteria for the entry of a test into the prevalidation process). Depending on the potential risk, immediate confirmation requiring testing beyond the information foreseen in Annexes VII or VIII or proposed confirmation requiring testing beyond the information foreseen in Annexes IX or X for the respective tonnage level may be necessary. If the results obtained from the use of such in vitro methods do not indicate a certain dangerous property, the relevant test shall nevertheless be carried out at the appropriate tonnage level to confirm the negative result, unless testing is not required in accordance with Annexes VII to X or the other rules in this Annex. Such confirmation may be waived, waived if the following conditions are met: (1) results are derived from an in vitro method whose scientific validity has been established by a validation study, according to internationally agreed validation principles; (2) results are adequate for the purpose of classification and labelling and/or risk assessment; and (3) adequate and reliable documentation of the applied method is provided. When nanoforms are covered by the registration the above approach in points (1) to (3) shall address the nanoforms separately. 1.5. Grouping of substances and read-across approach Substances whose physicochemical, toxicological and ecotoxicological eco-toxicological properties are likely to be similar or follow a regular pattern as a result of structural similarity may be considered as a group, or category of substances. Application of the group concept requires that physicochemical properties, human health effects and environmental effects or environmental fate may be predicted from data for reference substance(s) within the group by interpolation to other substances in the group (read-across approach). This avoids the need to test every substance for every endpoint. The Agency, after consulting with relevant stakeholders and other interested parties, shall issue guidance on technically and scientifically justified methodology for the grouping of substances sufficiently in advance of the first registration deadline for phase-in substances. When nanoforms are covered by the registration the above approach shall address the nanoforms separately. For grouping different nanoforms of the same substance the molecular structural similarities alone cannot serve as a justification. If nanoforms covered by a registration are grouped or placed in a category with other forms, including other nanoforms, of the substance in the same registration the obligations above shall apply in the same manner. The similarities may be based on: (1) a common functional group; (2) the common precursors and/or the likelihood of common breakdown products via physical and biological processes, which result in structurally similar chemicals; or (3) a constant pattern in the changing of the … 614 unchanged words … during all manufacturing and production stages including the waste management of the substance during these stages. 3.3. The specific conditions of use must be communicated through the supply chain in accordance with Article 31 or 32, as the case may be.

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ANNEX XII GENERAL PROVISIONS FOR DOWNSTREAM USERS TO ASSESS SUBSTANCES AND PREPARE CHEMICAL SAFETY REPORTS INTRODUCTION The purpose of this Annex is to set out how downstream users are to assess and document that the risks arising from the substance(s) they use are adequately controlled during their use for a use not covered by the Safety Data Sheet supplied to them and that other users further down the supply chain can adequately control the risks. The assessment shall cover the life-cycle of the substance, from its receipt by the downstream user, for his own uses and for his identified uses further down the supply chain. The assessment shall consider the use of the substance on its own, in a mixture or in an article. The assessment shall address all nanoforms that are covered by the registration. Justifications and conclusions drawn from the assessment shall be relevant to the nanoforms, from their receipt by the downstream user, for his own uses and for his identified uses further down the supply chain. In carrying out the chemical safety assessment and producing the Chemical Safety Report, the downstream user shall take account of information received from the supplier of the chemical in accordance with Article 31 and 32 of this Regulation. When nanoforms of the substance are covered by his own use or his identified uses down the supply chain, an appropriate metric for the assessment and presentation of the results in steps 1- 6 of the chemical safety assessment under 0.6.1 and 0.6.2 shall be considered, with the justification included in the chemical safety report and summarised in the safety data sheet. A multiple metric presentation is preferable, ensuring availability of mass metric information. Where available and appropriate, an assessment carried out under Community legislation, (e.g. risk assessments completed under Regulation (EEC) No 793/93) shall be taken into account in the chemical safety assessment and be reflected in the Chemical Safety Report. Deviations from such assessments shall be justified. Assessments carried out under other international and national programmes may also be taken into account. The process which the downstream user goes through in carrying out the chemical safety assessment and in producing his Chemical Safety Report, involves three steps: STEP 1: DEVELOPMENT OF EXPOSURE SCENARIO(S) The downstream user shall develop exposure scenarios for uses not covered in a Safety Data Sheet supplied to him in accordance with Section 5 of Annex I. STEP 2: IF NECESSARY, A REFINEMENT OF THE HAZARD ASSESSMENT BY THE SUPPLIER If the downstream user considers the hazard and PBT assessments reported in the Safety Data Sheet supplied to him to be appropriate, then no further hazard assessment or PBT and vPvB assessment is necessary. In this case he shall use the relevant information reported by the supplier for the risk characterisation. This shall be stated in the Chemical Safety Report. When nanoforms of the substance are covered by his own use or his identified uses down the supply chain, the assessment shall cover the hazard, PBT and vPvB assessment of nanoforms(s) as used. If the downstream user considers the assessments reported in the Safety Data Sheet supplied to him to be inappropriate, then he shall carry out the relevant assessments in accordance with Sections 1 to 4 of Annex I as appropriate to him. In those cases where the downstream user considers that information information, in addition to that provided by the supplier supplier, is necessary for producing his Chemical Safety Report Report, the downstream user shall gather this information. Where this information can only be obtained by testing on vertebrate animals, he shall submit a proposal for a testing strategy to the Agency in accordance with Article 38. He shall explain why he considers that additional information is necessary. While waiting for results of further testing, he shall record in his chemical safety report the risk management measures intended to manage the risks being explored that he has put in place. The above record taking shall address all nanoforms that are covered by his own uses or his identified uses down the supply chain. Such information shall be relevant to the nanoforms. On completion of any additional testing, the downstream user shall revise the Chemical Safety Report, and his Safety Data Sheet if he is required to prepare one, as appropriate. STEP 3: RISK CHARACTERISATION A risk characterisation shall be carried out for each new exposure scenario as prescribed in Section 6 of Annex I. The risk characterisation shall be presented under the relevant heading of the Chemical Safety Report and summarised in the Safety Data Sheet under the relevant heading(s). When generating an exposure scenario it will be necessary to make initial assumptions about the operating conditions and risk managements measures. If the initial assumptions lead to a risk characterisation indicating inadequate protection of human health and the environment, then it shall be necessary to carry out an iterative process with amendment of one or a number of factors until adequate control can be demonstrated. This may require the generation of additional hazard or exposure information or appropriate alteration of the process, operating conditions or risk management measures. Therefore, iterations may be made between on the one hand developing and revising an (initial) exposure scenario, which includes developing and implementing risk management measures, and on the other hand generating further information to produce the definitive exposure scenario. The purpose of generating further information is to establish a more precise risk characterisation, based on a refined hazard assessment and/or exposure assessment. The downstream user shall produce a Chemical Safety Report detailing his chemical safety assessment using Part B, Sections 9 and 10, of the format set out in Section 7 of Annex I and the other sections of this format, if appropriate. Part A of the Chemical Safety Report shall include a declaration that the risk management measures outlined in the relevant exposure scenarios are implemented by the downstream user for his own uses and that the risk management measures outlined in the exposure scenarios for the identified uses are communicated down the supply chain.