REACH: Information to be submitted in the technical dossier depending on tonnage
Toxicological Information
≥1 t/a | ≥10 t/a | ≥100 t/a | ≥1000 t/a | |
Toxicological information | ||||
8.1 Skin irritation or skin corrosion | ||||
The 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. Specific Rules: Steps 3 and 4 do not need to be conducted if:
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8.1.1 In vivo skin irritation
Specific Rules: The study does not need to be conducted if:
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X | X | X | |
8.2 Eye irritation | ||||
The 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 eye irritation. Specific Rule: Step 3 does not need to be conducted if:
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X | X | X | X |
8.2.2 In vivo eye irritation
Specific Rules: The study does not need to be conducted if:
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X | X | X | |
8.3 Skin sensitisation | ||||
The assessment of this endpoint shall comprise the following consecutive steps:
(1) an assessment of the available human, animal and alternative data, (2) In vivo testing. Specific Rules: Step 2 does not need to be conducted if:
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X | X | X | X |
8.4. Mutagenicity | ||||
8.4.1 In vitro gene mutation study in bacteria
Specific Rule: Further mutagenicity studies shall be considered in case of a positive result. |
X | X | X | X |
8.4.2 In vitro cytogenicity study in mammalian cells or in vitro micronucleus study
Specific Rules: The study does not usually need to be conducted
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X | X | X | |
8.4.3 In vitro gene mutation study in mammalian cells,
if a negative result in Annex VII, Section 8.4.1. and Annex VIII, Section 8.4.2. Specific Rule: The study does not usually need to be conducted if adequate data from a reliable in vivo mammalian gene mutation test are available. |
X | X | X | |
Specific Rule: Appropriate in vivo mutagenicity studies shall be considered in case of a positive result in any of the genotoxicity studies in Annex VII or VIII. | X | X | X | |
Specific Rules:
If there is a positive result in any of the in vitro genotoxicity studies in Annex VII or VIII and there are no results available from an in vivo study already, an appropriate in vivo somatic cell genotoxicity study shall be proposed by the registrant. If there is a positive result from an in vivo somatic cell study available, the potential for germ cell mutagenicity should be considered on the basis of all available data, including toxicokinetic evidence. If no clear conclusions about germ cell mutagenicity can be made, additional investigations shall be considered. |
X | X | ||
Specific Rules: If there is a positive result in any of the in vitro genotoxicity studies in Annexes VII or VIII, a second in vivo somatic cell test may be necessary, depending on the quality and relevance of all the available data.
If there is a positive result from an in vivo somatic cell study available, the potential for germ cell mutagenicity should be considered on the basis of all available data, including toxicokinetic evidence. If no clear conclusions about germ cell mutagenicity can be made, additional investigations shall be considered. |
X | |||
8.5 Acute toxicity | ||||
Specific Rule: The study/ies do(es) not generally need to be conducted if:
— the substance is classified as corrosive to the skin. |
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8.5.1 By oral route
Specific Rule: The study need not be conducted if a study on acute toxicity by the inhalation route (8.5.2) is available. |
X | X | X | X |
Specific Rule: In addition to the oral route (8.5.1), for substances other than gases, the information mentioned under 8.5.2 to 8.5.3 shall be provided for at least one other route. The choice for the second route will depend on the nature of the substance and the likely route of human exposure. If there is only one route of exposure, information for only that route need be provided. | X | X | X | |
8.5.2. By inhalation
Specific Rule: 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. |
X | X | X | |
8.5.3. By dermal route
Specific Rule:Testing by the dermal route is appropriate if:
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X | X | X | |
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
Specific Rules: The short-term toxicity study (28 days) does not need to be conducted if:
The appropriate route shall be chosen on the following basis: Testing by the dermal route is appropriate if:
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:
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:
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X | X | X | |
Unless already provided as part of Annex VIII requirements or if tests according to Section 8.6.2 of Annex IX is proposed. In this case, Section 3 of Annex XI shall not apply. | X | X | ||
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. Specific Rules:The sub-chronic toxicity study (90 days) does not need to be conducted if:
The appropriate route shall The appropriate route shall be chosen on the following basis: Testing by the dermal route is appropriate if:
Testing by the inhalation route is appropriate if:
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:
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X | X | ||
8.6.3. Long-term repeated toxicity study (≥ 12 months)
Specific Rules: 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 study is appropriate and one of the following conditions is met:
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X | |||
8.6.4. Further repeated dose toxicity studies
Specific Rules: 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:
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X | |||
8.7. Reproductive toxicity | ||||
8.7.1. Screening for reproductive/ developmental toxicity, one species (OECD 421 or 422),
if there is no evidence from available information on structurally related substances, from (Q)SAR estimates or from in vitro methods that the substance may be a developmental toxicant Specific Rules:This study does not need to be conducted if:
If a substance is known to have an adverse effect on fertility, meeting the criteria for classification as Repr Cat 1 or 2: R60, and the available data are adequate to support a robust risk assessment, then no further testing for fertility will be necessary. However, testing for development toxicity must be considered.
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Specific Rules:The studies do not need to be conducted if:
— the substance is known to be a genotoxic carcinogen and appropriate risk management measures are implemented, or — the substance is known to be a germ cell mutagen and appropriate risk management measures are implemented, or — the substance is of low toxicological activity (no evidence of toxicity seen in any of the tests available), it can be proven from toxicokinetic data that no systemic absorption occurs via relevant routes of exposure (e.g. plasma/blood concentrations below detection limit using a sensitive method and absence of the substance and of metabolites of the substance in urine, bile or exhaled air) and there is no or no significant human exposure. If a substance is known to have an adverse effect on fertility, meeting the criteria for classification as Repr Cat 1 or 2: R60, and the available data are adequate to support a robust risk assessment, then no further testing for fertility will be necessary. However, testing for development toxicity must be considered.
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X | X | ||
8.7.2. Pre-natal developmental toxicity study, one species, most appropriate route of administration, having regard to the likely route of human exposure (B.31 of the Commission Regulation on test methods as specified in Article 13(3) or OECD 414)
Specific Rule:The study shall be initially performed on one species. A decision on the need to perform a study at this tonnage level or the next on a second species should be based on the outcome of the first test and all other relevant available data. |
X | X | ||
8.7.2. Developmental toxicity study, one species, most appropriate route of administration, having regard to the likely route of human exposure (OECD 414) | X | |||
8.7.3. Two-generation reproductive toxicity study, one species, male and female, most appropriate route of administration, having regard to the likely route of human exposure,
if the 28-day or 90-day study indicates adverse effects on reproductive organs or tissues Specific Rule:The study shall be initially performed on one species. A decision on the need to perform a study at this tonnage level or the next on a second species should be based on the outcome of the first test and all other relevant available date. |
X | X | ||
Unless already provided as part of Annex IX requirements | X | |||
8.8. Toxicokinetics | ||||
8.8.1. Assessment of the toxicokinetic behaviour of the substance to the extent that can be derived from the relevant available information | X | X | X | |
8.9. Carcenogenicity | ||||
8.9.1. Carcinogenicity study
Specific Rules:A carcinogenicity study may be proposed by the registrant or may be required by the Agency in accordance with Articles 40 or 41 if:
If the substance is classified as mutagen category 1 or 2, the default presumption would be that a genotoxic mechanism for carcinogenicity is likely. In these cases, a carcinogenicity test will normally not be required. |
X |