in force 2022-10-14 MODIFIED+2,522 −422§
Amended by Regulation (EU) 2022/477 32022R0477
applies from: unchanged
Sources disagree about what is listed, not about the text — the text comparison and the EU's own amendment metadata found this change; the amending act's instructions do not mention it. All are shown; none is overruled.
Section 8.4 on mutagenicity now sets out a detailed follow-up testing sequence, requiring the registrant to perform an in vitro study referenced in Annex VIII point 8.4.2 after a positive in vitro gene mutation result, and to propose (or have the Agency require) an in vivo study referenced in Annex IX point 8.4.4 based on positive genotoxicity results, addressing chromosomal aberration or gene mutation concerns as appropriate, and it adds circumstances under which the bacterial gene mutation test and follow-up testing need not be conducted, whereas the earlier text only stated that further mutagenicity studies should be considered after a positive result.
Point 8.4.1 now specifies that when the in vitro gene mutation study in bacteria is not conducted for nanoforms because it is not appropriate, an in vitro study referenced in Annex VIII point 8.4.3 shall be provided, replacing the prior wording that referred generally to one or more in vitro mutagenicity studies in mammalian cells under Annex VIII sections 8.4.2 and 8.4.3 or other internationally recognised in vitro methods.
In section 9.1.1, the adaptation condition changed from referring to "mitigating factors" indicating aquatic toxicity is unlikely, or adequate information for environmental classification and labelling being available, to referring to "factors" indicating short-term aquatic toxicity is unlikely, and the long-term Daphnia study rule in Annex IX point 9.1.5 was rewritten to state that the registrant may propose, or the Agency may require, such testing when short-term testing is unlikely to provide a true measure of intrinsic aquatic toxicity, including a numeric water solubility threshold of below 1 mg/L.
Cited: Annex VII, v2 · Annex VII, v1
text before / after
02006R1907-20220501 → 02006R1907-20221014
ANNEX VII
STANDARD INFORMATION REQUIREMENTS FOR SUBSTANCES MANUFACTURED OR IMPORTED IN QUANTITIES OF ONE TONNE OR MORE
This 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.