... (75) The possibility of introducing restrictions on the manufacturing, placing on the market and use of dangerous substances, preparations and articles applies to all substances falling within the scope of this Regulation, with minor exemptions. Restrictions on the placing on the market and the use of substances which are carcinogenic, mutagenic or toxic to reproduction, category 1 or 2, for their use by consumers on their own or in preparations should continue to be introduced. ...

... (76) Experience at international level shows that substances with characteristics rendering them persistent, liable to bioaccumulate and toxic, or very persistent and very liable to bioaccumulate, present a very high concern, while criteria have been developed allowing the identification of such substances. For certain other substances concerns are sufficiently high to address them in the same way on a case-by-case basis. The criteria in Annex XIII should be reviewed taking into account the current and any new experience in the identification of these substances and if appropriate, be amended with a view to ensuring a high level of protection for human health and the environment. ...

... (115) Resources should be focused on substances of the highest concern. A substance should therefore be added to Annex I of Directive 67/548/EEC if it meets the criteria for classification as carcinogenic, mutagenic or toxic for reproduction categories 1, 2 or 3, as a respiratory sensitiser, or in respect of other effects on a case-by-case basis. Provision should be made to enable competent authorities to submit proposals to the Agency. The Agency should give its opinion on the proposal while interested parties should have an opportunity to comment. The Commission should take a decision subsequently. ...

... (d) persistent, bioaccumulative and toxic (PBT) and very persistent and very bioaccumulative (vPvB) assessment. ...

... (a) phase-in substances classified as carcinogenic, mutagenic or toxic to reproduction, category 1 or 2, in accordance with Directive 67/548/EEC and manufactured in the Community or imported, in quantities reaching one tonne or more per year per manufacturer or per importer, at least once after 1 June 2007; ...

... (b) phase-in substances classified as very toxic to aquatic organisms which may cause long-term adverse effects in the aquatic environment (R50/53) in accordance with Directive 67/548/EEC, and manufactured in the Community or imported in quantities reaching 100 tonnes or more per year per manufacturer or per importer, at least once after 1 June 2007; ...

... (b) where a substance is persistent, bioaccumulative and toxic or very persistent and very bioaccumulative in accordance with the criteria set out in Annex XIII; or ...

... (b) in an individual concentration of ≥ 0,1 % by weight for non-gaseous preparations at least one substance that is persistent, bioaccumulative and toxic or very persistent and very bioaccumulative in accordance with the criteria set out in Annex XIII or has been included for reasons other than those referred to in point (a) in the list established in accordance with Article 59(1); or ...

... 1. The Agency shall examine any testing proposal set out in a registration or a downstream user report for provision of the information specified in Annexes IX and X for a substance. Priority shall be given to registrations of substances which have or may have PBT, vPvB, sensitising and/or carcinogenic, mutagenic or toxic for reproduction (CMR) properties, or substances classified as dangerous according to Directive 67/548/EEC above 100 tonnes per year with uses resulting in widespread and diffuse exposure. ...

... (c) substances meeting the criteria for classification as toxic for reproduction category 1 or 2 in accordance with Directive 67/548/EEC; ...

... (d) substances which are persistent, bioaccumulative and toxic in accordance with the criteria set out in Annex XIII of this Regulation; ...

... (f) substances — such as those having endocrine disrupting properties or those having persistent, bioaccumulative and toxic properties or very persistent and very bioaccumulative properties, which do not fulfil the criteria of points (d) or (e) — for which there is scientific evidence of probable serious effects to human health or the environment which give rise to an equivalent level of concern to those of other substances listed in points (a) to (e) and which are identified on a case-by-case basis in accordance with the procedure set out in Article 59. ...

... (c) substances identified under Article 57(f) having persistent, bioaccumulative and toxic properties or very persistent and very bioaccumulative properties. ...

... 2. For a substance on its own, in a preparation or in an article which meets the criteria for classification as carcinogenic, mutagenic or toxic to reproduction, category 1 or 2, and could be used by consumers and for which restrictions to consumer use are proposed by the Commission, Annex XVII shall be amended in accordance with the procedure referred to in Article 133(4). Articles 69 to 73 shall not apply. ...

... 1. Harmonised classification and labelling at Community level shall, from 1 June 2007, normally be added to Annex I of Directive 67/548/EEC for classification of a substance as carcinogenic, mutagenic or toxic for reproduction category 1, 2 or 3, or as a respiratory sensitiser. Harmonised classification and labelling for other effects may also be added to Annex I of Directive 67/548/EEC on a case-by-case basis if justification is provided demonstrating the need for action at Community level. To this end, Member State competent authorities may submit proposals to the Agency for harmonised classification and labelling in accordance with Annex XV. ...

... 1. By 1 June 2019, the Commission shall carry out a review to assess whether or not to extend the application of the obligation to perform a chemical safety assessment and to document it in a chemical safety report to substances not covered by this obligation because they are not subject to registration or subject to registration but manufactured or imported in quantities of less than 10 tonnes per year. However, for substances meeting the criteria for classification as carcinogenic, mutagenic or toxic for reproduction, category 1 or 2, in accordance with Directive 67/548/EEC, the review shall be carried out by 1 June 2014. When carrying out the review the Commission shall take into account all relevant factors, including: ...

... 5. The Commission shall carry out a review of Annex XIII by 1 December 2008, to assess the adequacy of the criteria for identifying substances which are persistent, bioaccumulative and toxic or very persistent and very bioaccumulative, with a view to proposing an amendment to it, if appropriate, in accordance with the procedure referred to in Article 133(4). ...

... (c) substances that are persistent, bioaccumulative and toxic or very persistent and very bioaccumulative in accordance with the criteria set out in Annex XIII, if the concentration of an individual substance is equal to or greater than 0,1 %. ...

... (b) ≥ 0,1 % by weight and the substances are persistent, bioaccumulative and toxic or very persistent and very bioaccumulative in accordance with the criteria set out in Annex XIII. ...

... 8.1.Skin irritation or skin corrosionThe assessment of this endpoint shall comprise the following consecutive steps:(1)an assessment of the available human and animal data,(2)an assessment of the acid or alkaline reserve,(3)in vitro study for skin corrosion,(4)in vitro study for skin irritation. | 8.1.Steps 3 and 4 do not need to be conducted if:the available information indicates that the criteria are met for classification as corrosive to the skin or irritating to eyes, orthe substance is flammable in air at room temperature, orthe substance is classified as very toxic in contact with skin, oran acute toxicity study by the dermal route does not indicate skin irritation up to the limit dose level (2000 mg/kg body weight). | ...

... 8.1.1.In vivo skin irritation | 8.1.1.The study does not need to be conducted if:the substance is classified as corrosive to the skin or as a skin irritant, orthe substance is a strong acid (pH ≤ 2,0) or base (pH ≥ 11,5), orthe substance is flammable in air at room temperature, orthe substance is classified as very toxic in contact with skin, oran acute toxicity study by the dermal route does not indicate skin irritation up to the limit dose level (2000 mg/kg body weight). | ...

... 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. | 8.6.1.The short-term toxicity study (28 days) does not need to be conducted if:a reliable sub-chronic (90 days) or chronic toxicity study is available, provided that an appropriate species, dosage, solvent and route of administration were used, orwhere a substance undergoes immediate disintegration and there are sufficient data on the cleavage products, orrelevant human exposure can be excluded in accordance with Annex XI Section 3.The appropriate route shall be chosen on the following basis:Testing by the dermal route is appropriate if:(1)inhalation of the substance is unlikely; and(2)skin contact in production and/or use is likely; and(3)the physicochemical and toxicological properties suggest potential for a significant rate of absorption through the skin.Testing by the inhalation route is appropriate if exposure of humans via inhalation is likely taking into account the vapour pressure of the substance and/or the possibility of exposure to aerosols, particles or droplets of an inhalable size.The sub-chronic toxicity study (90 days) (Annex IX, Section 8.6.2) shall be proposed by the registrant if: the frequency and duration of human exposure indicates that a longer term study is appropriate;and one of the following conditions is met:other available data indicate that the substance may have a dangerous property that cannot be detected in a short-term toxicity study, orappropriately designed toxicokinetic studies reveal accumulation of the substance or its metabolites in certain 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, ortoxicity of particular concern (e.g. serious/severe effects), orindications 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), orthe 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, orparticular 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), oreffects 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. | ...

... 8.6.2.Sub-chronic toxicity study (90-day), one species, rodent, male and female, most appropriate route of administration, having regard to the likely route of human exposure. | 8.6.2.The sub-chronic toxicity study (90 days) does not need to be conducted if:a reliable short-term toxicity study (28 days) is available showing severe toxicity effects according to the criteria for classifying the substance as R48, for which the observed NOAEL-28 days, with the application of an appropriate uncertainty factor, allows the extrapolation towards the NOAEL-90 days for the same route of exposure, ora reliable chronic toxicity study is available, provided that an appropriate species and route of administration were used, ora substance undergoes immediate disintegration and there are sufficient data on the cleavage products (both for systemic effects and effects at the site of uptake), orthe substance is unreactive, insoluble and not inhalable and there is no evidence of absorption and no evidence of toxicity in a 28-day "limit test", particularly if such a pattern is coupled with limited human exposure.The appropriate route shall be chosen on the following basis:Testing by the dermal route is appropriate if:(1)skin contact in production and/or use is likely; and(2)the physicochemical properties suggest a significant rate of absorption through the skin; and(3)one of the following conditions is met:toxicity is observed in the acute dermal toxicity test at lower doses than in the oral toxicity test, orsystemic effects or other evidence of absorption is observed in skin and/or eye irritation studies, orin vitro tests indicate significant dermal absorption, orsignificant dermal toxicity or dermal penetration is recognised for structurally-related substances.Testing by the inhalation route is appropriate if:exposure of humans via inhalation is likely taking into account the vapour pressure of the substance and/or the possibility of exposure to aerosols, particles or droplets of an inhalable size.Further studies shall be proposed by the registrant or may be required by the Agency in accordance with Articles 40 or 41 in case of:failure to identify a NOAEL in the 90 days study unless the reason for the failure to identify a NOAEL is absence of adverse toxic effects, ortoxicity of particular concern (e.g. serious/severe effects), orindications 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), orparticular 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). | ...

... CRITERIA FOR THE IDENTIFICATION OF PERSISTENT, BIOACCUMULATIVE AND TOXIC SUBSTANCES, AND VERY PERSISTENT AND VERY BIOACCUMULATIVE SUBSTANCES ...

... (i) persistent, bioaccumulative and toxic substances (PBT-substances), and ...

... - the substance is classified as carcinogenic (category 1 or 2), mutagenic (category 1 or 2), or toxic for reproduction (category 1, 2, or 3), or ...

... 28.Substances which appear in Annex I to Directive 67/548/EEC classified as carcinogen category 1 or carcinogen category 2 and labelled at least as "Toxic (T) "with risk phrase R 45: "May cause cancer "or risk phrase R49: "May cause cancer by inhalation", and listed as follows:Carcinogen category 1 listed in Appendix 1.Carcinogen category 2 listed in Appendix 2. | Without prejudice to the other parts of this Annex the following shall apply to entries 28 to 30: 1.Shall not be used in substances and preparations placed on the market for sale to the general public in individual concentration equal to or greater than:either the relevant concentration specified in Annex I to Directive 67/548/EEC, orthe relevant concentration specified in Directive 1999/45/EC. | ...

... 30.Substances which appear in Annex I to Directive 67/548/EEC classified as toxic to reproduction category 1 or toxic to reproduction category 2 and labelled with risk phrase R60: "May impair fertility "and/or R61: "May cause harm to the unborn child", and listed as follows:Toxic to reproduction category 1 listed in Appendix 5.Toxic to reproduction category 2 listed in Appendix 6. | 2.By way of derogation, paragraph 1 shall not apply to:(a)medicinal or veterinary products as defined by Directive 2001/82/EC and Directive 2001/83/EC;(b)cosmetic products as defined by Council Directive 76/768/EEC;(c)motor fuels which are covered by Directive 98/70/EC,mineral oil products intended for use as fuel in mobile or fixed combustion plants,fuels sold in closed systems (e.g. liquid gas bottles);(d)artists' paints covered by Directive 1999/45/EC. | ...

... 30.Substances which appear in Annex I to Directive 67/548/EEC classified as toxic to reproduction category 1 or toxic to reproduction category 2 and labelled with risk phrase R60: "May impair fertility "and/or R61: "May cause harm to the unborn child", and listed as follows:Toxic to reproduction category 1 listed in Appendix 5.Toxic to reproduction category 2 listed in Appendix 6. | 2.By way of derogation, paragraph 1 shall not apply to:(a)medicinal or veterinary products as defined by Directive 2001/82/EC and Directive 2001/83/EC;(b)cosmetic products as defined by Council Directive 76/768/EEC;(c)motor fuels which are covered by Directive 98/70/EC,mineral oil products intended for use as fuel in mobile or fixed combustion plants,fuels sold in closed systems (e.g. liquid gas bottles);(d)artists' paints covered by Directive 1999/45/EC. | ...

... 30.Substances which appear in Annex I to Directive 67/548/EEC classified as toxic to reproduction category 1 or toxic to reproduction category 2 and labelled with risk phrase R60: "May impair fertility "and/or R61: "May cause harm to the unborn child", and listed as follows:Toxic to reproduction category 1 listed in Appendix 5.Toxic to reproduction category 2 listed in Appendix 6. | 2.By way of derogation, paragraph 1 shall not apply to:(a)medicinal or veterinary products as defined by Directive 2001/82/EC and Directive 2001/83/EC;(b)cosmetic products as defined by Council Directive 76/768/EEC;(c)motor fuels which are covered by Directive 98/70/EC,mineral oil products intended for use as fuel in mobile or fixed combustion plants,fuels sold in closed systems (e.g. liquid gas bottles);(d)artists' paints covered by Directive 1999/45/EC. | ...

... 30.Substances which appear in Annex I to Directive 67/548/EEC classified as toxic to reproduction category 1 or toxic to reproduction category 2 and labelled with risk phrase R60: "May impair fertility "and/or R61: "May cause harm to the unborn child", and listed as follows:Toxic to reproduction category 1 listed in Appendix 5.Toxic to reproduction category 2 listed in Appendix 6. | 2.By way of derogation, paragraph 1 shall not apply to:(a)medicinal or veterinary products as defined by Directive 2001/82/EC and Directive 2001/83/EC;(b)cosmetic products as defined by Council Directive 76/768/EEC;(c)motor fuels which are covered by Directive 98/70/EC,mineral oil products intended for use as fuel in mobile or fixed combustion plants,fuels sold in closed systems (e.g. liquid gas bottles);(d)artists' paints covered by Directive 1999/45/EC. | ...

... Substances with specific effects on human health (see chapter 4 of Annex VI of Directive 67/548/EEC) that are classified as carcinogenic, mutagenic and/or toxic for reproduction in categories 1 or 2 are ascribed Note E if they are also classified as very toxic (T+), toxic (T) or harmful (Xn). For these substances, the risk phrases R20, R21, R22, R23, R24, R25, R26, R27, R28, R39, R68 (harmful), R48 and R65 and all combinations of these risk phrases shall be preceded by the word "Also". ...

... Substances with specific effects on human health (see chapter 4 of Annex VI of Directive 67/548/EEC) that are classified as carcinogenic, mutagenic and/or toxic for reproduction in categories 1 or 2 are ascribed Note E if they are also classified as very toxic (T+), toxic (T) or harmful (Xn). For these substances, the risk phrases R20, R21, R22, R23, R24, R25, R26, R27, R28, R39, R68 (harmful), R48 and R65 and all combinations of these risk phrases shall be preceded by the word "Also". ...

... Substances with specific effects on human health (see chapter 4 of Annex VI of Directive 67/548/EEC) that are classified as carcinogenic, mutagenic and/or toxic for reproduction in categories 1 or 2 are ascribed Note E if they are also classified as very toxic (T+), toxic (T) or harmful (Xn). For these substances, the risk phrases R20, R21, R22, R23, R24, R25, R26, R27, R28, R39, R68 (harmful), R48 and R65 and all combinations of these risk phrases shall be preceded by the word "Also". ...

... Point 30 — Toxic to reproduction: category 1 ...

... Point 30 — Toxic to reproduction: category 2 ...