L 136/116

Official Journal of the European Union

EN29.5.2007

ANNEX XSTANDARD INFORMATION REQUIREMENTS FOR SUBSTANCES MANUFACTURED OR IMPORTED IN
QUANTITIES OF 1 000 TONNES OR MORE (1)At the level of this Annex, the registrant must submit a proposal and a time schedule for fulfilling the information
requirements of this Annex in accordance with Article 12(1)(e).

Column 1 of this Annex establishes the standard information required for all substances manufactured or imported inquantities of 1 000 tonnes or more in accordance with Article 12(1)(e). Accordingly, the information required in column
1 of this Annex is additional to that required in column 1 of Annexes VII, VIII and IX. Any other relevant physicochemical, toxicological and ecotoxicological information that is available shall be provided. Column 2 of this Annex lists
specific rules according to which the registrant may propose to omit the required standard information, replace it byother information, provide it at a later stage or adapt it in another way. If the conditions are met under which column 2of this Annex allows an adaptation to be proposed, the registrant shall clearly state this fact and the reasons for proposing
each adaptation under the appropriate headings in the registration dossier.

In addition to these specific rules, a registrant may propose to adapt the required standard information set out incolumn 1 of this Annex according to the general rules contained in Annex XI. In this case as well, he shall clearly state
the reasons for any decision to propose adaptations to the standard information under the appropriate headings in theregistration dossier referring to the appropriate specific rule(s) in column 2 or in Annex XI ( 2).

Before new tests are carried out to determine the properties listed in this Annex, all available in vitro data, in vivo data,
historical human data, data from valid (Q)SARs and data from structurally related substances (read-across approach) shallbe assessed first. In vivo testing with corrosive substances at concentration/dose levels causing corrosivity shall be avoided.
Prior to testing, further guidance on testing strategies should be consulted in addition to this Annex.

When, for certain endpoints, it is proposed not to provide information for other reasons than those mentioned incolumn 2 of this Annex or in Annex XI, this fact and the reasons shall also be clearly stated.

8. TOXICOLOGICAL INFORMATIONCOLUMN 1
STANDARD INFORMATIONREQUIREDCOLUMN 2
SPECIFIC RULES FOR ADAPTATION FROM COLUMN 1

8.4.

If there is a positive result in any of the in vitro genotoxicity studies in Annexes VII or VIII, a second invivo 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 noclear conclusions about germ cell mutagenicity can be made, additional investigations shall be considered.

8.6.3. A long-term repeated toxicity study (≥ 12 months) may be proposed by the registrant or required by theAgency in accordance with Articles 40 or 41 if the frequency and duration of human exposure indicatesthat a longer term study is appropriate and one of the following conditions is met:
— serious or severe toxicity effects of particular concern were observed in the 28-day or 90-day study forwhich the available evidence is inadequate for toxicological evaluation or risk characterisation, or— effects shown in substances with a clear relationship in molecular structure with the substance being
studied were not detected in the 28-day or 90-day study, or— the substance may have a dangerous property that cannot be detected in a 90-day study.

(1) This Annex shall apply to producers of articles that are required to register in accordance with Article 7 and to other downstream users thatare required to carry out tests under this Regulation adapted as necessary.
(2) Note: conditions for not requiring a specific test that are set out in the appropriate test methods in the Commission Regulation on test
methods as specified in Article 13(3) that are not repeated in column 2, also apply.

29.5.2007

Official Journal of the European Union

ENCOLUMN 1
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COLUMN 2
SPECIFIC RULES FOR ADAPTATION FROM COLUMN 1

8.6.4. 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:— toxicity of particular concern (e.g. serious/severe effects), or— indications of an effect for which the available evidence is inadequate for toxicological evaluation and/or risk characterisation. In such cases it may also be more appropriate to perform specific toxicologicalstudies that are designed to investigate these effects (e.g. immunotoxicity, neurotoxicity), or— particular concern regarding exposure (e.g. use in consumer products leading to exposure levels which
are close to the dose levels at which toxicity is observed).

8.7.

Reproductive toxicity

8.7.

The studies need not 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 ofexposure (e.g. plasma/blood concentrations below detection limit using a sensitive method andabsence of the substance and of metabolites of the substance in urine, bile or exhaled air) and there isno 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.
If a substance is known to cause developmental toxicity, meeting the criteria for classification as Repr Cat
1 or 2: R61, and the available data are adequate to support a robust risk assessment, then no further
testing for developmental toxicity will be necessary. However, testing for effects on fertility must beconsidered.

8.7.2. Developmental toxicity study,
one species, most appropriate
routeofadministration,
having regard to the likely
route of human exposure(OECD 414).

8.7.3. Two-generation reproductive
toxicity study, one species,
male and female, mostappropriate route of administration, having regard to thelikely route of human exposure, unless already provided
as part of Annex IX requirements

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 mutagen category 3 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 substances 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 berequired.

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Official Journal of the European Union

EN

29.5.2007

9. ECOTOXICOLOGICAL INFORMATIONCOLUMN 1
STANDARD INFORMATIONREQUIRED

9.2.

Degradation

COLUMN 2
SPECIFIC RULES FOR ADAPTATION FROM COLUMN 1

9.2.

Further biotic degradation testing shall be proposed if the chemical safety assessment according to Annex I
indicates the need to investigate further the degradation of the substance and its degradation products.
The choice of the appropriate test(s) depends on the results of the chemical safety assessment and may
include simulation testing in appropriate media (e.g. water, sediment or soil).

9.2.1. Biotic
9.3.

Fate and behaviour in theenvironment

9.3.4. Further information on theenvironmental fate and behaviour of the substance and/ordegradation products

9.3.4. Further testing shall be proposed by the registrant or may be required by the Agency in accordance withArticles 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 theresults of the chemical safety assessment.

9.4.

9.4.

Effects on terrestrial organisms

Long-term toxicity testing shall be proposed by the registrant if the results of the chemical safety assessment according to Annex I indicates the need to investigate further the effects of the substance and/ordegradation products on terrestrial organisms. The choice of the appropriate test(s) depends on theoutcome 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 alreadyprovided as part of Annex IX
requirements.
9.4.6. Long-term toxicity testing onplants,unlessalreadyprovided 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 if the results of the chemical safety assessment indicates the need to investigate further the effects of the substance and/or relevant degradation
products on sediment organisms. The choice of the appropriate test(s) depends on the results of thechemical 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 thatis 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 wereperformed using the analytical method concerned. If the analytical methods are not available this shall be justified.