Registration, Evaluation, Authorisation and Restriction of Chemicals

02006R1907-20220501 → 02006R1907-20221014

ANNEX VI INFORMATION REQUIREMENTS REFERRED TO IN ARTICLE 10 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 … 1,135 unchanged words … 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 email address 1.1.2. Contact person 1.1.3. Location of the registrant's production and own use site(s), as appropriate 1.1.4. Where an only representative has been appointed in accordance with Article 8(1), the following information regarding the natural or legal person established outside the Union who appointed the only representative: name, address, telephone number, email address, contact person, location of the production site(s) or formulation site(s), as appropriate, company website, as appropriate and national company identification number(s), as appropriate. 1.2. Joint submission of data Articles 11 or and 19 foresee that provide for the possibility for the lead registrant to submit parts of the registration may be submitted by a lead registrant information on behalf of other member registrants. In this case, When, in accordance with Article 11(1), the lead registrant submits information referred to in Article 10, point (a)(iv), (vi), (vii) and (ix), the lead registrant shall identify describe the other registrants specifying: their name, address, telephone number, fax number composition(s), nanoform or set of similar nanoforms to which this information relates in accordance with points 2.3.1 to 2.3.4 and e-mail address, parts subsection 2.4 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 Annex. Each member registrant shall identify the lead registrant submitting relying on his behalf specifying: his name, address, telephone number, fax number and e-mail address, parts of the registration which are information submitted by the lead registrant. Mention registrant shall indicate which information thus submitted pertains to which composition, nanoform or set of similar nanoforms of the number(s) given substance that the registrant identifies in accordance with Article 10, point (a)(ii), and Article 11(1). When, in accordance with Article 11(3), a registrant submits information referred to in Article 10, point (a)(iv), (vi), (vii) or (ix), separately, this Annex registrant shall describe the composition(s), nanoform or Annexes VII set of similar nanoforms of the substance to X, as appropriate. which this information relates in accordance with points 2.3.1 to 2.3.4 and subsection 2.4 of this Annex. 1.3 Third party appointed under Article 4 1.3.1. Name, address, telephone number, fax number and e-mail email 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 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 and any other identifier of each substance 2.1.1. Name(s) in the IUPAC nomenclature or nomenclature. If unavailable, other international chemical name(s) 2.1.2. Other names (usual name, trade name, abbreviation) 2.1.3. EINECS EC number, i.e. Einecs, Elincs or ELINCs NLP number, or the number assigned by the Agency (if available and appropriate) 2.1.4. CAS name and CAS number (if available) 2.1.5. Other identity code code, such as customs number (if available) 2.2. Information related to molecular and structural formula or crystal structure of each substance 2.2.1. Molecular formula and structural formula (including SMILES notation, notation and other representation if available) and description of crystal structure(s) 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. 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 (%) (%), if applicable 2.3.2. Nature Names of impurities, including isomers constituents and by-products impurities In the case of a substance of unknown or variable composition, complex reaction products or biological materials (UVCB): names of constituents present at a concentration of ≥ 10 %; names of known constituents present at a concentration of < 10 %; for constituents that cannot be identified individually, description of groups of constituents based on chemical nature; description of the origin or source and the manufacturing process 2.3.3. Percentage Typical concentration and concentration range (in percentage) of (significant) main constituents, groups of constituents that cannot be identified individually and impurities as specified in point 2.3.2 2.3.4. Nature Names and order typical concentration and concentration range (in percentage) of magnitude (… ppm, … %) additives 2.3.5. All necessary qualitative analytical data specific for the identification of any additives (e.g. stabilising agents or inhibitors) 2.3.5. Spectral data (e.g. the substance, such as ultra-violet, infra-red, nuclear magnetic resonance resonance, mass spectrum or mass spectrum) diffraction data 2.3.6. High-pressure liquid chromatogram, gas chromatogram All necessary quantitative analytical data specific for the identification of the substance, such as chromatographic, titrimetric, elemental analysis or diffraction data 2.3.7. Description of the analytical methods or the appropriate bibliographical references that are necessary for the identification of the substance (including the identification and quantification of its constituents and, where appropriate, for the identification of its impurities and additives. additives). The description shall consist of the experimental protocols followed and the relevant interpretation of the results reported under points 2.3.1 to 2.3.6. This information shall be sufficient to allow the methods to be reproduced 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. subsection (2.4). The description shall consist of the experimental protocols followed and the relevant interpretation of the results reported under points 2.4.2 to 2.4.5. This information shall be sufficient to allow the methods to be reproduced. 2.5. Any other available information relevant for the identification of the substance 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 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 … 366 unchanged words … 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.

02006R1907-20220501 → 02006R1907-20221014

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 … 2,163 unchanged words … skin sensitisation studies that were carried out or initiated before 10 May 2017, and that meet the requirements set 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 In case of a positive result. result in the in vitro gene mutation study in bacteria referred to in point 8.4.1 of this Annex, which gives rise to concern, the registrant shall perform an in vitro study referred to in Annex VIII, point 8.4.2. Based on the positive result of any of those in vitro genotoxicity studies, the registrant shall propose, or the Agency may require, an appropriate in vivo study referred to in Annex IX, point 8.4.4. The in vivo study shall address the chromosomal aberration concern or the gene mutation concern or both, as appropriate. The in vitro gene mutation study in bacteria does not need to be conducted if this test is not applicable for the substance. In this case, the registrant shall provide a justification and perform an in vitro study referred to in Annex VIII, point 8.4.3. In case of a positive result in that study the registrant shall perform an in vitro cytogenicity study referred to in Annex VIII, point 8.4.2. Based on the positive result in any of those in vitro genotoxicity studies, or in case one of the Annex VIII in vitro tests is not applicable for the substance, the registrant shall propose, or the Agency may require, an appropriate in vivo study referred to in Annex IX, point 8.4.4. The in vivo study shall address the chromosomal aberration concern or the gene mutation concern or both, as appropriate. The in vitro gene mutation study in bacteria referred to in point 8.4.1 and follow-up testing do not need to be conducted in any of the following cases: the substance is known to cause germ cell mutagenicity, meeting the criteria for classification in the hazard class germ cell mutagenicity category 1A or 1B, and appropriate risk management measures are implemented, the substance is known to be a genotoxic carcinogen, meeting the criteria for classification both in the hazard class germ cell mutagenicity category 1A, 1B or 2 and in the hazard class carcinogenicity category 1A or 1B, and appropriate risk management measures are implemented. 8.4.1. In vitro gene mutation study in bacteria 8.4.1. The in vitro gene mutation study in bacteria does not need to be conducted for nanoforms where it is not appropriate. In this case other studies involving one or more such case, an in vitro mutagenicity study(ies) study referred to in mammalian cells (Annex Annex VIII, sections 8.4.2. and 8.4.3 or other internationally recognised in vitro methods) point 8.4.3, 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: in any of the following cases: there are mitigating factors indicating that short-term 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, 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 registrant may propose long-term toxicity testing instead of short-term toxicity testing. Long-term toxicity testing on invertebrates (preferred species Daphnia), (Annex IX, point 9.1.5) shall be proposed by the registrant or may be required by the Agency when it is unlikely that short-term toxicity testing can provide a true measure of the intrinsic aquatic toxicity study on Daphnia (Annex IX, section 9.1.5.) shall be considered of the substance, for instance: if the substance is poorly water soluble, soluble (solubility below 1 mg/L), or for nanoforms if they have with 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.

02006R1907-20220501 → 02006R1907-20221014

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 … 729 unchanged words … 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. The studies referred to in points 8.4.2 and 8.4.3 do not need to be conducted in any of the following cases: adequate data from the corresponding in vivo study, (namely in vivo chromosomal aberration (or micronucleus) study regarding point 8.4.2 or in vivo mammalian gene mutation study regarding point 8.4.3), are available, the substance is known to cause germ cell mutagenicity, meeting the criteria for classification as germ cell mutagen category 1A or 1B, and appropriate risk management measures are implemented, the substance is known to be a genotoxic carcinogen, meeting the criteria for classification both in the hazard class germ cell mutagenicity category 1A, 1B or 2 and in the hazard class carcinogenicity category 1A or 1B, and appropriate risk management measures are implemented. In case of a positive result in any of the in vitro genotoxicity studies referred to in Annex VII or this Annex, which gives rise to concern, the registrant shall propose, or the Agency may require, an appropriate in vivo study referred to in Annex IX, point 8.4. The in vivo study shall address the chromosomal aberration concern or the gene mutation concern or both as appropriate. In case an in vitro mutagenicity study referred to in points 8.4.2 or 8.4.3 is not applicable for the substance, the registrant shall provide a justification and shall propose or the Agency may require an appropriate in vivo study referred to in Annex IX, point 8.4.4. The in vivo study shall address the chromosomal aberration concern or the gene mutation concern or both as appropriate. 8.4.2. In vitro cytogenicity mammalian chromosomal aberration study in mammalian cells or in vitro mammalian 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 … 633 unchanged words … 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, 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 toxicity (OECD TG 421 or 422), TG 422); the preferred species is the rat. The route of administration shall be oral if there is no evidence from available information on structurally related substances, from (Q)SAR estimates or from in vitro methods that the substance is a solid or liquid, and inhalation if the substance is a gas; deviations may be a developmental toxicant made if scientifically justified, for example through evidence of equivalent or higher systemic exposure via another relevant route of human exposure or route-specific toxicity. 8.7.1. This study does not need to be conducted if: in any of the following cases: the substance is known to be a genotoxic carcinogen carcinogen, meeting the criteria for classification both in the hazard class germ cell mutagenicity category 1A, 1B or 2 and in the hazard class carcinogenicity category 1A or 1B, and appropriate risk management measures are implemented, or the substance is known to be a germ cell mutagen mutagen, meeting the criteria for classification in the hazard class germ cell mutagenicity category 1A or 1B and appropriate risk management measures are implemented, or relevant human exposure can be excluded in accordance with Annex XI section XI, Section 3, or a pre-natal developmental toxicity study (Annex (OECD TG 414) referred to in Annex IX, 8.7.2) or, either point 8.7.2 or an Extended One-Generation Reproductive Toxicity Study (B.56, OECD (OECD TG 443) (Annex referred to in Annex IX, section 8.7.3) point 8.7.3 is available or proposed by the registrant; or a two-generation study (B.35, OECD Two-Generation Reproductive Toxicity Study (OECD TG 416), 416) is available. If available, a substance is known to have an adverse effect on sexual function or fertility, meeting the criteria for classification as toxic for reproduction in the hazard class reproductive toxicity 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 in the hazard class reproductive toxicity 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. assessment. In cases where there are case of serious concerns about the potential for adverse effects on sexual function, fertility or development, the registrant shall propose, or the Agency may require either an Extended One-Generation Reproductive Toxicity Study (Annex (OECD TG 443), referred to in Annex IX, section 8.7.3) point 8.7.3, or a pre-natal developmental toxicity study (Annex (OECD TG 414), referred to in Annex IX, section 8.7.2) may, as appropriate, be proposed by the registrant point 8.7.2, instead of the screening study. study (OECD TG 421 or 422) to address those concerns. Those serious concerns include among others: adverse effects related to sexual function, fertility or development based on available information, not meeting the criteria for classification as reproductive toxicity category 1A or 1B, possible developmental or reproductive toxicity of the substance predicted from information on structurally related substances, (Q)SAR estimates or in vitro methods. 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. 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. Aquatic toxicity 9.1. Long-term aquatic toxicity testing referred to in Annex IX, subsection 9.1, in addition to short-term toxicity testing shall be proposed by the registrant or may be required by the Agency if the chemical safety assessment performed in accordance with Annex I indicates that it is needed to further investigate the effects on aquatic organisms, for example when further information is needed for the refinement of the PNEC or if additional toxicity information as set out in Annex XIII, point 3.2.3, would be necessary to assess PBT or vPvB properties of the substance. The choice of the appropriate test(s) shall be made on the basis of the results of the chemical safety assessment. 9.1.3. Short-term toxicity testing on fish: the registrant may consider long-term toxicity testing instead of short-term. fish 9.1.3. The study does not need to be conducted if: in any of the following cases: there are mitigating factors indicating that short-term 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. The registrant may propose long-term toxicity testing instead of short-term toxicity testing. Long-term toxicity testing on fish referred to in Annex IX, point 9.1.6, shall be proposed by the registrant or may be required by the Agency when it is unlikely that short-term toxicity testing can provide a true measure of the intrinsic 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 substance, for instance: if the substance is poorly water soluble, soluble (below 1 mg/L), or for nanoforms if they have with 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 information on degradation shall be generated or further degradation testing as described in Annex IX shall be considered proposed if the chemical safety assessment according to performed in accordance with Annex I indicates the need that it is needed to further investigate further the degradation of the substance. That could for example be the case if additional information on degradation as set out in Annex XIII, point 3.2.1, is required to assess PBT or vPvB properties of the substance in accordance with subsection 2.1 of that Annex. 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 shall be made on the basis of the results of the chemical safety assessment. In case the generation of additional information requires further testing in accordance with Annex IX, the registrant shall propose or the Agency may require such testing. 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: in any of the following cases: the substance is readily biodegradable, or the substance is highly insoluble in water. water, based on the structure, the substance does not have chemical groups that can hydrolyse. 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. Further information on bioaccumulation shall be generated if additional information on bioaccumulation as set out in Annex XIII, point 3.2.2, is required to assess PBT or vPvB properties of the substance in accordance with subsection 2.1 of that Annex. In case the generation of additional information requires further testing in accordance with Annex IX or Annex X, the registrant shall propose or the Agency may require such testing. 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 partition coefficient), or the substance and its relevant degradation products decompose rapidly. The study may not be waived on the basis of low octanol-water partition coefficient alone, unless the adsorptive properties of the substance are solely driven by lipophilicity. For instance, the study may not be waived on the basis of low octanol-water partition coefficient alone if the substance is surface active or ionisable at environmental pH (pH 4 – 9). 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.

02006R1907-20220501 → 02006R1907-20221014

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 … 633 unchanged words … on the structure, the substance does not have any chemical group that can dissociate. 7.17. Viscosity For hydrocarbon substances the kinematic viscosity shall be determined at 40 °C. 8. TOXICOLOGICAL INFORMATION COLUMN 1 STANDARD INFORMATION REQUIRED COLUMN 2 SPECIFIC RULES FOR ADAPTATION FROM COLUMN 1 8.4. If Mutagenicity 8.4. The studies referred to in points 8.4.4 and 8.4.5 do not need to be conducted in any of the following cases: the substance is known to cause germ cell mutagenicity, meeting the criteria for classification in the hazard class germ cell mutagenicity category 1A or 1B, and appropriate risk management measures are implemented, the substance is known to be a genotoxic carcinogen, meeting the criteria for classification both in the hazard class germ cell mutagenicity category 1A, 1B or 2 and in the hazard class carcinogenicity category 1A or 1B, and appropriate risk management measures are implemented. 8.4.4. An appropriate in vivo mammalian somatic cell genotoxicity study, if there is a positive result in any of the in vitro genotoxicity studies referred to in Annex VII or VIII and there are no results available from an Annex VIII, which gives rise to concern. The in vivo study already, an appropriate in vivo mammalian somatic cell genotoxicity study shall address the chromosomal aberration concern or the gene mutation concern or both, as appropriate. 8.4.4. The in vivo mammalian somatic cell genotoxicity study does not need to be proposed by the registrant. If conducted if there are adequate results available from an appropriate in vivo mammalian somatic cell genotoxicity study. 8.4.5. An appropriate in vivo mammalian germ cell genotoxicity study, if there is a positive result from in an available in vivo mammalian somatic cell study available, the potential for genotoxicity study, which gives rise to concern. The in vivo mammalian germ cell mutagenicity should genotoxicity study shall address the chromosomal aberration concern or the gene mutation concern or both, as appropriate. 8.4.5. The study does not need to be considered on conducted if there is clear evidence that neither the basis of all available data, including toxicokinetic evidence. If no clear conclusions about substance nor its metabolites reach the germ cell mutagenicity can be made, additional investigations shall be considered. cells. 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, unless already provided as part of Annex VIII requirements or … 733 unchanged words … the hazard class reproductive toxicity (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 shall be necessary. 8.7.2. Pre-natal developmental toxicity study, study (OECD TG 414) on one species, most appropriate species; the preferred species is the rat or the rabbit. The route of administration, having regard to administration shall be oral if the likely substance is a solid or liquid, and inhalation if the substance is a gas; deviations may be made if scientifically justified, for example through evidence of equivalent or higher systemic exposure via another relevant route of human exposure (B.31 of or route-specific toxicity. 8.7.2. An additional pre-natal developmental toxicity study in a second species, that is the Commission Regulation on test methods as specified other preferred species to the one used in Article 13(3) or OECD 414). 8.7.2. The study the first study, shall be initially performed on one species. A decision on proposed by the need to perform registrant or may be required by the Agency if there is a study at this tonnage level or the next on a second species should be concern for developmental toxicity based on the outcome of the first test study and all other relevant available data. That could be the case for example if the study on the first species shows developmental toxicity not meeting the criteria for classification in the hazard class reproductive toxicity category 1A or 1B; May damage the unborn child (H360D). Deviations from the default route of administration and deviations in the choice of species shall be scientifically justified. 8.7.3. Extended One-Generation Reproductive Toxicity Study (B.56 of the Commission Regulation on test methods as specified in Article 13(3) or OECD (OECD TG 443), basic test design (cohorts 1A and 1B without extension to include a an F2 generation), one species, most appropriate route of administration, having regard to the likely route of human exposure, if the available repeated dose toxicity studies (e.g. 28-day or 90-day studies, or OECD TG 421 or 422 screening studies) indicate adverse effects on reproductive organs or tissues or reveal other concerns in relation with reproductive toxicity. The route of administration shall be oral if the substance is a solid or liquid, and inhalation if the substance is a gas; deviations may be made if scientifically justified, for example through evidence of equivalent or higher systemic exposure via another relevant route of human exposure or route-specific toxicity. 8.7.3. An Extended One-Generation Reproductive Toxicity Study with the extension of cohort 1B to include the F2 generation shall be proposed by the registrant or may be required by the Agency in accordance with Article 40 or 41, if: (a) the substance has uses leading to significant exposure of consumers or professionals, taking into account, inter alia, consumer exposure from articles, and (b) any of the following conditions are met: the substance displays genotoxic effects in somatic cell mutagenicity tests in vivo which could lead to classifying it as Mutagen Category 2, or there are indications that the internal dose for the substance and/or any of its metabolites will reach a steady state in the test animals only after an extended exposure, or there are indications of one or more relevant modes of action related to endocrine disruption from available in vivo studies or non-animal approaches. An Extended One-Generation Reproductive Toxicity Study including cohorts 2A/2B (developmental neurotoxicity) and/or cohort 3 (developmental immunotoxicity) shall be proposed by the registrant or may be required by the Agency in accordance with Article 40 or 41, in case of particular concerns on (developmental) neurotoxicity or (developmental) immunotoxicity justified by any of the following: existing information on the substance itself derived from relevant available in vivo or non-animal approaches (e.g. abnormalities of the CNS, evidence of adverse effects on the nervous or immune system in studies on adult animals or animals exposed prenatally), or specific mechanisms/modes of action of the substance with an association to (developmental) neurotoxicity and/or (developmental) immunotoxicity (e.g. cholinesterase inhibition or relevant changes in thyroidal hormone levels associated to adverse effects), or existing information on effects caused by substances structurally analogous to the substance being studied, suggesting such effects or mechanisms/modes of action. Other studies on developmental neurotoxicity and/or developmental immunotoxicity instead of cohorts 2A/2B (developmental neurotoxicity) and/or cohort 3 (developmental immunotoxicity) of the Extended One-Generation Reproductive Toxicity Study may be proposed by the registrant in order to clarify the concern on developmental toxicity. Two-generation reproductive toxicity studies (B.35, OECD TG 416) that were initiated before 13 March 2015 shall be considered appropriate to address this standard information requirement. The study shall be performed on one species. The need to perform a study at this tonnage level or the next on a second strain or a second species may be considered and a decision should be based on the outcome of the first test and all other relevant available data. 9. ECOTOXICOLOGICAL INFORMATION COLUMN 1 STANDARD INFORMATION REQUIRED COLUMN 2 SPECIFIC RULES FOR ADAPTATION FROM COLUMN 1 9.1. Aquatic toxicity 9.1. Long-term toxicity testing other than the tests referred to in points 9.1.5 and 9.1.6 shall be proposed by the registrant or may be required by the Agency if the chemical safety assessment according to performed in accordance with Annex I indicates the need that it is needed to further investigate further the effects of the substance on aquatic organisms. The choice of the appropriate test(s) depends shall be made on the basis of the results of the chemical safety assessment. 9.1.5. Long-term toxicity testing on invertebrates (preferred species Daphnia), (unless already provided as part of Annex VII requirements) 9.1.6. Long-term toxicity testing on fish, (unless already provided as part of Annex VIII requirements) requirements). The information shall be provided for one subpoint 9.1.6.1 or subpoint 9.1.6.3. 9.1.6. Fish short-term toxicity tests on embryo and sac-fry stages (OECD TG 212) that were initiated before 14 April 2022 shall be considered appropriate to address this standard information requirement provided that the substance is not highly lipophilic (log Kow > 4) or there is no indication of the Sections 9.1.6.1, 9.1.6.2 endocrine disrupting properties or 9.1.6.3. any other specific mode of action. 9.1.6.1. Fish early-life stage (FELS) toxicity test (OECD TG 210) 9.1.6.2. Fish short-term toxicity test on embryo and sac-fry stages 9.1.6.3. Fish, Fish juvenile growth test (OECD TG 215) 9.2. Degradation 9.2. Further biotic degradation testing shall be proposed by the registrant or may be required by the Agency if the chemical safety assessment according to performed in accordance with Annex I indicates the need that it is needed to further investigate further the degradation of the substance and its transformation or degradation products. The choice of the appropriate test(s) depends and test media shall be made on the basis of the results of the chemical safety assessment and may include simulation testing in appropriate media (e.g. water, sediment or soil). assessment. 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 transformation and abiotic and biotic 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. The study may not be waived on the basis of low octanol-water partition coefficient alone, unless the potential for bioaccumulation of the substance is solely driven by lipophilicity. For instance, the study may not be waived on the basis of low octanol-water partition coefficient alone if the substance is surface active or ionisable at environmental pH (pH 4 – 9). 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, 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. The study may not be waived on the basis of low octanol-water partition coefficient alone, unless the adsorptive properties of the substance are solely driven by lipophilicity. For instance, the study may not be waived on the basis of low octanol-water partition coefficient alone if the substance is surface active or ionisable at environmental pH (pH 4 – 9). 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 test(s) shall be made on the outcome basis of the results 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 propose or the Agency may require long-term toxicity testing as referred to in Annex X instead of short-term. short-term toxicity testing. 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.

02006R1907-20220501 → 02006R1907-20221014

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 … 506 unchanged words … information 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. 8. TOXICOLOGICAL INFORMATION COLUMN 1 STANDARD INFORMATION REQUIRED COLUMN 2 SPECIFIC RULES FOR ADAPTATION FROM COLUMN 1 8.4. If Mutagenicity 8.4. The studies referred to in points 8.4.6 and 8.4.7 do not need to be conducted in any of the following cases: the substance is known to cause germ cell mutagenicity, meeting the criteria for classification in the hazard class germ cell mutagenicity category 1A or 1B, and appropriate risk management measures are implemented, the substance is known to be a genotoxic carcinogen, meeting the criteria for classification both in the hazard class germ cell mutagenicity category 1A or 1B or 2 and in the hazard class carcinogenicity category 1A or 1B, and appropriate risk management measures are implemented. 8.4.6. A second in vivo mammalian somatic cell genotoxicity study, if there is a positive result in any of the in vitro genotoxicity studies referred to in Annexes Annex VII or Annex VIII, a which gives rise to both chromosomal aberration concern and gene mutation concern. The second study shall address chromosomal aberration or gene mutation, as appropriate, which has not been addressed by the first in vivo mammalian somatic cell genotoxicity study. 8.4.7. A second in vivo somatic mammalian germ cell test may be necessary, depending on the quality and relevance of all the available data. If genotoxicity study, if there is a positive result from an in in vivo mammalian somatic cell genotoxicity studies, which gives rise to both chromosomal aberration concern and gene mutation concern. The second study available, shall address the potential for chromosomal aberration or gene mutation, as appropriate, which has not been addressed by the first in vivo mammalian germ cell mutagenicity should genotoxicity study. 8.4.7. The study does not need to be considered on conducted if there is clear evidence that neither the basis of all available data, including toxicokinetic evidence. If no clear conclusions about substance nor its metabolites reach the germ cell mutagenicity can be made, additional investigations shall be considered. cells. 8.6.3. A long-term repeated toxicity study (≥ 12 months) may be proposed by the registrant or required by the Agency in accordance with Articles 40 or 41 if the frequency and duration of human exposure indicates that a longer term … 446 unchanged words … for classification in the hazard class reproductive toxicity (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 shall be necessary. 8.7.2. Developmental Pre-natal developmental toxicity study, one study (OECD TG 414) in a second species, most appropriate the preferred species is the rat or the rabbit, whichever was not used in the first study under Annex IX. The route of administration, having regard to administration shall be oral if the likely substance is a solid or liquid, and inhalation if the substance is a gas; deviations may be made if scientifically justified, for example through evidence of equivalent or higher systemic exposure via another relevant route of human exposure (OECD 414). or route-specific toxicity. Deviations from the default route of administration and deviations in the choice of species shall be scientifically justified. 8.7.3. Extended One-Generation Reproductive Toxicity Study (B.56 of the Commission Regulation on test methods as specified in Article 13(3) or OECD (OECD TG 443), basic test design (cohorts 1A and 1B without extension to include a an F2 generation), one species, most appropriate route of administration, having regard to the likely route of human exposure, unless already provided as part of Annex IX requirements. The route of administration shall be oral if the substance is a solid or liquid, and inhalation if the substance is a gas; deviations may be made if scientifically justified, for example through evidence of equivalent or higher systemic exposure via another relevant route of human exposure or route-specific toxicity. 8.7.3. An Extended One-Generation Reproductive Toxicity Study with the extension of cohort 1B to include the F2 generation shall be proposed by the registrant or may be required by the Agency in accordance with Article 40 or 41, if: (a) the substance has uses leading to significant exposure of consumers or professionals, taking into account, inter alia, consumer exposure from articles, and (b) any of the following conditions are met: the substance displays genotoxic effects in somatic cell mutagenicity tests in vivo which could lead to classifying it as Mutagen Category 2, or there are indications that the internal dose for the substance and/or any of its metabolites will reach a steady state in the test animals only after an extended exposure, or there are indications of one or more relevant modes of action related to endocrine disruption from available in vivo studies or non-animal approaches. An Extended One-Generation Reproductive Toxicity Study including cohorts 2A/2B (developmental neurotoxicity) and/or cohort 3 (developmental immunotoxicity) shall be proposed by the registrant or may be required by the Agency in accordance with Article 40 or 41, in case of particular concerns on (developmental) neurotoxicity or (developmental) immunotoxicity justified by any of the following: existing information on the substance itself derived from relevant available in vivo or non-animal approaches (e.g. abnormalities of the CNS, evidence of adverse effects on the nervous or immune system in studies on adult animals or animals exposed prenatally), or specific mechanisms/modes of action of the substance with an association to (developmental) neurotoxicity and/or (developmental) immunotoxicity (e.g. cholinesterase inhibition or relevant changes in thyroidal hormone levels associated to adverse effects), or existing information on effects caused by substances structurally analogous to the substance being studied, suggesting such effects or mechanisms/modes of action. Other studies on developmental neurotoxicity and/or developmental immunotoxicity instead of cohorts 2A/2B (developmental neurotoxicity) and/or cohort 3 (developmental immunotoxicity) of the Extended One-Generation Reproductive Toxicity Study may be proposed by the registrant in order to clarify the concern on developmental toxicity. Two-generation reproductive toxicity studies (B.35, OECD TG 416) that were initiated before 13 March 2015 shall be considered appropriate to address this standard information requirement. 8.9.1. Carcinogenicity study 8.9.1. A carcinogenicity study may be proposed by the registrant or may be required by the Agency in accordance with Articles 40 or 41 if: the substance has a widespread dispersive use or there is evidence of frequent or long-term human exposure, and the substance is classified as germ cell mutagen category 2 or there is evidence from the repeated dose study(ies) that the substance is able to induce hyperplasia and/or pre-neoplastic lesions. If the substance is classified as germ cell mutagen category 1A or 1B, the default presumption would be that a genotoxic mechanism for carcinogenicity is likely. In these cases, a carcinogenicity test will normally not be required. 9. ECOTOXICOLOGICAL INFORMATION COLUMN 1 STANDARD INFORMATION REQUIRED COLUMN 2 SPECIFIC RULES FOR ADAPTATION FROM COLUMN 1 9.2. Degradation 9.2. Further biotic degradation testing shall be proposed by the registrant or may be required by the Agency, if the chemical safety assessment according to performed in accordance with Annex I indicates the need that it is needed to further investigate further the degradation of the substance and its transformation and degradation products. The choice of the appropriate test(s) depends and test media shall be made on the basis of the results of the chemical safety assessment and may include simulation testing in appropriate media (e.g. water, sediment or soil). assessment. 9.2.1. Biotic 9.3. Fate and behaviour in the environment 9.3.4. Further information on the environmental fate and behaviour of the substance and/or degradation products 9.3.4. Further testing shall be proposed by the registrant or may be required by the Agency in accordance with Articles 40 or 41 if the chemical safety assessment according to Annex I indicates the need to investigate further the fate and behaviour of the substance. The choice of the appropriate test(s) depends on the results of the chemical safety assessment. 9.4. Effects on terrestrial organisms 9.4. Long-term toxicity testing shall be proposed by the registrant or may be required by the Agency if the results of the chemical safety assessment according to performed in accordance with Annex I indicates the need that it is needed to further investigate further the effects of the substance and/or or of transformation and degradation products on terrestrial organisms. The choice of the appropriate test(s) depends shall be made on the basis of the outcome of the chemical safety assessment. These studies do not need to be conducted if direct and indirect exposure of the soil compartment is unlikely. 9.4.4. Long-term toxicity testing on invertebrates, unless already provided as part of Annex IX requirements. 9.4.6. Long-term toxicity testing on plants, unless already provided as part of Annex IX requirements. 9.5.1. Long-term toxicity to sediment organisms 9.5.1. Long-term toxicity testing shall be proposed by the registrant or may be required by the Agency if the results of the chemical safety assessment performed in accordance with Annex I indicates the need that it is needed to further investigate further the effects of the substance and/or or of relevant transformation and degradation products on sediment organisms. The choice of the appropriate test(s) depends shall be made on the basis of the results of the chemical safety assessment. 9.6.1. Long-term or reproductive toxicity to birds 9.6.1. Any need for testing should be carefully considered taking into account the large mammalian dataset that is usually available at this tonnage 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.