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ANNEX VIIISTANDARD INFORMATION REQUIREMENTS FOR SUBSTANCES MANUFACTURED OR IMPORTED IN
QUANTITIES OF 10 TONNES OR MORE (1)Column 1 of this Annex establishes the standard information required for all substances manufactured or imported inquantities of 10 tonnes or more in accordance with Article 12(1)(c). Accordingly, the information required in column 1of this Annex is additional to that required in column 1 of Annex VII. Any other relevant physicochemical, toxicologicaland ecotoxicological information that is available shall be provided. Column 2 of this Annex lists specific rules according
to which the required standard information may be omitted, replaced by other information, provided at a different stageor adapted in another way. If the conditions are met under which column 2 of this Annex allows adaptations, the registrant shall clearly state this fact and the reasons for each adaptation under the appropriate headings in the registration
dossier.
In addition to these specific rules, a registrant may adapt the required standard information set out in column 1 of thisAnnex according to the general rules contained in Annex XI. In this case as well, he shall clearly state the reasons for any
decision to adapt the standard information under the appropriate headings in the registration dossier referring to theappropriate 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, information is not provided for other reasons than those mentioned in column 2 of thisAnnex or in Annex XI, this fact and the reasons shall also be clearly stated.

8. TOXICOLOGICAL INFORMATIONCOLUMN 1
STANDARD INFORMATIONREQUIRED

8.1.

Skin irritation

8.1.1.

In vivo skin irritation

8.2.

Eye irritation8.2.1.

In vivo eye irritation

8.4.

Mutagenicity

8.4.2.

In vitro cytogenicity study
in mammalian cells or invitro micronucleus study

COLUMN 2
SPECIFIC RULES FOR ADAPTATION FROM COLUMN 1

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, or— the substance is a strong acid (pH ≤ 2,0) or base (pH ≥ 11,5), or— the substance is flammable in air at room temperature, or— the substance is classified as very toxic in contact with skin, or— an acute toxicity study by the dermal route does not indicate skin irritation up to the limit doselevel (2 000 mg/kg body weight).

8.2.1.

The study does not need to be conducted if:— the substance is classified as irritating to eyes with risk of serious damage to eyes, or— the substance is classified as corrosive to the skin and provided that the registrant classified thesubstance as eye irritant, or— the substance is a strong acid (pH ≤ 2,0) or base (pH ≥ 11,5), or— the substance is flammable in air at room temperature.

8.4.2.

The study does not usually need to be conducted— if adequate data from an in vivo cytogenicity test are available, or— the substance is known to be carcinogenic category 1 or 2 or mutagenic category 1, 2 or 3.

(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.

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STANDARD INFORMATIONREQUIRED

8.4.3.

In vitro gene mutation study
in mammalian cells, if anegative result in Annex VII,Section
8.4.1.
andAnnex VIII, Section 8.4.2.

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SPECIFIC RULES FOR ADAPTATION FROM COLUMN 1

8.4.3.

The study does not usually need to be conducted if adequate data from a reliable in vivo mammaliangene mutation test are available.

8.4.

Appropriate in vivo mutagenicity studies shall be considered in case of a positive result in any of thegenotoxicity studies in Annex VII or VIII.

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.
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.

8.5.2.

By inhalation

8.5.2.

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 ordroplets of an inhalable size.

8.5.3.

By dermal route

8.5.3.

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.

8.6.

Repeated dose toxicity

8.6.1.

Short-term repeated dose
toxicity study (28 days),
one species, male andfemale, 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, or— where a substance undergoes immediate disintegration and there are sufficient data on the cleavage
products, or— relevant 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 ordroplets of an inhalable size.
The sub-chronic toxicity study (90 days) (Annex IX, Section 8.6.2) shall be proposed by the registrant if:
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SPECIFIC RULES FOR ADAPTATION FROM COLUMN 1

and one of the following conditions is met:
— other available data indicate that the substance may have a dangerous property that cannot bedetected in a short-term toxicity study, or— appropriately 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 accordancewith 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, or— toxicity of particular concern (e.g. serious/severe effects), or— indications 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 toxicologicalstudies that are designed to investigate these effects (e.g. immunotoxicity, neurotoxicity), or— the route of exposure used in the initial repeated dose study was inappropriate in relation to theexpected route of human exposure and route-to-route extrapolation cannot be made, 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 to humans may be expected), or— effects 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.

8.7.

Reproductive toxicity

8.7.1.

Screening for reproductive/developmental toxicity, onespecies (OECD 421 or422), 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

8.7.1.

This study does 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 areimplemented, or— relevant human exposure can be excluded in accordance with Annex XI section 3, or— a pre-natal developmental toxicity study (Annex IX, 8.7.2) or a two-generation reproductive toxicity
study (Annex IX, Section 8.7.3) is available.
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
be considered.
In cases where there are serious concerns about the potential for adverse effects on fertility or development, either a pre-natal developmental toxicity study (Annex IX, Section 8.7.2) or a two-generation
reproductive toxicity study (Annex IX, Section 8.7.3) may be proposed by the registrant instead of thescreening study.

8.8.

Toxicokinetics

8.8.1.

Assessment of the toxicokinetic behaviour of thesubstance to the extent thatcan be derived from therelevant available information

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9. ECOTOXICOLOGICAL INFORMATIONCOLUMN 1
STANDARD INFORMATIONREQUIRED

9.1.3.

Short-term toxicity testing
on fish: the registrant may
consider long-term toxicity
testing instead of shortterm.

COLUMN 2
SPECIFIC RULES FOR ADAPTATION FROM COLUMN 1

9.1.3.

The study does not need to be conducted if:— there are mitigating factors indicating that aquatic toxicity is unlikely to occur, for instance if thesubstance is highly insoluble in water or the substance is unlikely to cross biological membranes, or— a long-term aquatic toxicity study on fish is available.
Long-term aquatic toxicity testing as described in Annex IX shall be considered if the chemical safetyassessment according to Annex I indicates the need to investigate further effects on aquatic organisms.
The choice of the appropriate test(s) will depend on the results of the chemical safety assessment.
The long-term aquatic toxicity study on fish (Annex IX, Section 9.1.6) shall be considered if thesubstance is poorly water soluble.

9.1.4.

Activated sludge respiration
inhibition testing

9.1.4.

The study does not need to be conducted if:— there is no emission to a sewage treatment plant, or— there are mitigating factors indicating that microbial toxicity is unlikely to occur, for instance thesubstance is highly insoluble in water, or— the substance is found to be readily biodegradable and the applied test concentrations are in therange of concentrations that can be expected in the influent of a sewage treatment plant.
The study may be replaced by a nitrification inhibition test if available data show that the substance islikely to be an inhibitor of microbial growth or function, in particular nitrifying bacteria.

9.2.

Degradation

9.2.

Further degradation testing shall be considered if the chemical safety assessment according to Annex I
indicates the need to investigate further the degradation of the substance. The choice of the appropriate
test(s) will depend on the results of the chemical safety assessment.

9.2.2.

Abiotic

9.2.2.1. Hydrolysis as a function ofpH.

9.3.

Fate and behaviour in theenvironment

9.3.1.

Adsorption/desorption
screening

9.2.2.1. The study does not need to be conducted if:— the substance is readily biodegradable, or— the substance is highly insoluble in water.

9.3.1.

The study does not need to be conducted if:— based on the physicochemical properties the substance can be expected to have a low potential foradsorption (e.g. the substance has a low octanol water partition coefficient), or— the substance and its relevant degradation products decompose rapidly.