(3)

Annex VIII is amended as follows: (a) in subsection 8.4, in column 2, the following text is added: ‘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.’; (b) in point 8.4.2, in column 1, the text is replaced by the following: ‘8.4.2. In vitro mammalian chromosomal aberration study or in vitro mammalian micronucleus study’; (c) in point 8.4.2, the text in column 2 is deleted; (d) in point 8.4.3, the text in column 2 is deleted; (e) in point 8.6.1, in column 2, the introductory wording of the sixth paragraph is replaced by the following: ‘Further studies shall be proposed by the registrant or may be required by the Agency in case of:’; (f) point 8.7.1 is replaced by the following: ‘8.7.1. Screening for reproductive/developmental toxicity (OECD TG 421 or TG 422); the preferred species is the rat. 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. 8.7.1. This study does not need to be conducted in any of the following cases: — 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, — the substance is known to be a germ cell mutagen, meeting the criteria for classification in the hazard class germ cell mutagenicity category 1A or 1B and appropriate risk management measures are implemented, — relevant human exposure can be excluded in accordance with Annex XI, Section 3, — a pre-natal developmental toxicity study (OECD TG 414) referred to in Annex IX, point 8.7.2 or an Extended One-Generation Reproductive Toxicity Study (OECD TG 443) referred to in Annex IX, point 8.7.3 is available or proposed by the registrant; or a Two-Generation Reproductive Toxicity Study (OECD TG 416) is available, — a substance is known to have an adverse effect on sexual function or fertility, meeting the criteria for classification 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, — a substance is known to cause developmental toxicity, meeting the criteria 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. In case of serious concerns about potential 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 (OECD TG 443), referred to in Annex IX, point 8.7.3, or a pre-natal developmental toxicity study (OECD TG 414), referred to in Annex IX, point 8.7.2, instead of the screening 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.’; (g) in point 8.8.1, in column 2, the first paragraph is replaced by the following: ‘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 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’; (h) the following subsection 9.1 is inserted: ‘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.’; (i) point 9.1.3 is replaced by the following: ‘9.1.3. Short-term toxicity testing on fish 9.1.3. The study does not need to be conducted in any of the following cases: — there are 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, — 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 of the substance, for instance: — if the substance is poorly water soluble (below 1 mg/L), or — for nanoforms with low dissolution rate in the relevant test media.’; (j) in subsection 9.2, in column 2, the text is replaced by the following: ‘9.2. Further information on degradation shall be generated or further degradation testing as described in Annex IX shall be proposed if the chemical safety assessment performed in accordance with Annex I indicates that it is needed to further investigate 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) 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.’; (k) in subpoint 9.2.2.1, in column 2, the text is replaced by the following: ‘9.2.2.1. The study does not need to be conducted in any of the following cases: — the substance is readily biodegradable, — the substance is highly insoluble in 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.’; (l) in subsection 9.3, in column 2, the following text is added: ‘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.’;