Annex X

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.