Annex IX

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.