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L 98/38 EN Official Journal of the European Union 25.3.2022
COMMISSION REGULATION (EU) 2022/477
of 24 March 2022
amending Annexes VI to X to Regulation (EC) No 1907/2006 of the European Parliament and of the
Council concerning the Registration, Evaluation, Authorisation and Restriction of Chemicals
(REACH)
(Text with EEA relevance)
THE EUROPEAN COMMISSION,
Having regard to the Treaty on the Functioning of the European Union,
Having regard to Regulation (EC) No 1907/2006 of the European Parliament and of the Council of 18 December 2006
concerning the Registration, Evaluation, Authorisation and Restriction of Chemicals (REACH), establishing a European
Chemicals Agency, amending Directive 1999/45/EC and repealing Council Regulation (EEC) No 793/93 and Commission
Regulation (EC) No 1488/94 as well as Council Directive 76/769/EEC and Commission Directives 91/155/EEC,
93/67/EEC, 93/105/EC and 2000/21/EC(1), and in particular Article 131 thereof,
Whereas:
(1) Regulation (EC) No 1907/2006 lays down specific registration duties and obligations on manufacturers, importers
and downstream users to generate data on substances they manufacture, import or use, to assess the risks related to
those substances and to develop and recommend appropriate risk management measures.
(2) Annex VI to Regulation (EC) No 1907/2006 sets out information requirements referred to in Article 10, point (a)(i)
to (v) and (x), of that Regulation. Annexes VII to X to that Regulation set out standard information requirements for
substances manufactured or imported in quantities of 1 tonne or more, 10 tonnes or more, 100 tonnes or more and
1 000tonnes or more.
(3) In June 2019, the Commission and the European Chemicals Agency (‘the Agency’) concluded in the REACH
Evaluation Joint Action Plan(2) that certain information requirements in the Annexes to Regulation (EC)
No 1907/2006 should be amended to provide more clarity on the obligations of registrants regarding the
submission of information.
(4) To increase clarity of the registrants’ obligations, a number of information requirements in Annexes VII to X to
Regulation (EC) No 1907/2006 and the general rules for adaptation of the standard testing regime in Annex XI to
that Regulation have been amended by Commission Regulation (EU) 2021/979(3)but in line with the objectives of
the REACH Evaluation Joint Action Plan a number of information requirements remain to be clarified.
(5) Requirements concerning the general registrant information and substance identification information which a
registrant is to submit for general registration purposes, laid down in Annex VI, sections 1 and 2, to Regulation (EC)
No 1907/2006 should therefore be amended.
(1) OJ L 396, 30.12.2006, p. 1.
(2) European Commission and European Chemicals Agency REACH Evaluation Joint Action Plan of June 2019 (https://echa.europa.eu/
documents/10162/21877836/final_echa_com_reach_evaluation_action_plan_en.pdf/0003c9fc-652e-5f0b-90f9-dff9d5371d17).
(3) Commission Regulation (EU) 2021/979 of 17 June 2021 amending Annexes VII to XI to Regulation (EC) No 1907/2006 of the
European Parliament and of the Council concerning the Registration, Evaluation, Authorisation and Restriction of Chemicals (REACH)
(OJ L 216, 18.6.2021, p. 121).25.3.2022 EN Official Journal of the European Union L 98/39
(6) Certain specific rules for adaptation from the standard information requirements set out in Annexes VII to X to
Regulation (EC) No 1907/2006 should be amended to align the terminology of the classification of hazardous
substances to that used in Annex I, parts 2 to 5, to Regulation (EC) No 1272/2008 of the European Parliament and
the Council(4).
(7) Specific rules for adaptation from the standard information laid down in Annex VII to Regulation (EC)
No 1907/2006 on mutagenicity and aquatic toxicity should be amended for reasons of clarity and to ensure that
useful information is provided. In particular, subsection 8.4 should be amended to clarify the consequences of a
positive result in the in vitro gene mutation study, as well as the situations when the study required under point
8.4.1 does not need to be conducted. In addition, parts not referring to standard information required should be
removed from column 1 of point 9.1.1, while column 2 of that point should describe more accurately the
situations where the study does not need to be conducted and where long-term aquatic toxicity testing is required.
Point 9.1.2 should also be modified to clarify when the study does not need to be conducted.
(8) The information requirements on testing for mutagenicity and for reproductive toxicity, and on ecotoxicological
information in Annex VIII to Regulation (EC) No 1907/2006 should be amended in order to clarify the obligations
of registrants. In particular, the rules on testing for mutagenicity in subsection 8.4 should specify the situations that
do not require testing referred to in that Annex and the situations that require further testing referred to in Annex IX.
Furthermore, the nomenclature of the studies in point 8.4.2 should be aligned with that of the corresponding
technical guidance documents of the Organisation for Economic Cooperation and Development (OECD)(5). In
addition, to ensure that useful information on reproductive and developmental toxicity is generated, the preferred
animal species and the preferred administration routes for testing should be added to point 8.7.1, while certain
specific rules for adaptation from the standard information requirements should be clarified. Finally, a subsection
heading 9.1 for aquatic toxicity that was missing should be added and the information requirement on short-term
toxicity testing on fish in point 9.1.3 should be amended in order to remove the parts that do not list standard
information from column 1 and to clarify the situations when the test is not required in column 2. Subsections 9.2
on degradation and 9.3 on fate and behaviour in the environment should also be modified in order to better
describe the situations requiring further information on degradation and bioaccumulation as well as further
degradation and bioaccumulation studies.
(9) Information requirements on testing for mutagenicity in Annex IX to Regulation (EC) No 1907/2006 should be
amended to specify in points 8.4.4 and 8.4.5 the studies to be conducted in mammalian somatic cells and, when
relevant, in mammalian germ cells, as well as the cases where such studies need to be conducted. In addition, the
information requirements in point 8.7.2 on testing for pre-natal developmental toxicity in a first and second species
and in point 8.7.3 for Extended One-Generation Reproductive Toxicity studies should be clarified with regard to the
preferred animal species and the preferred administration routes for testing, as well as with regard to the possible
deviations from the general rules. Finally, as regards the section on ecotoxicological information, certain
information requirements on long-term toxicity testing on fish should be removed due to animal welfare reasons.
The subsection 9.2 on degradation should also be amended to align the wording of point 9.2.3 concerning
identification of degradation products with that of the related provision in Annex XIII, and to reflect the amended
requirement on further degradation testing accordingly. The subsection 9.4 on effects on terrestrial organisms
should also be amended to clarify that a long-term toxicity study should be proposed by the registrant or may be
required by the Agency for substances that have a high potential to adsorb to soil or that are very persistent.
(10) Annex X to Regulation (EC) No 1907/2006 should be amended to clarify certain information requirements on
mutagenicity, developmental and reproductive toxicity and ecotoxicological information. In particular, the
amendments should describe the situations meeting the requirement for a second in-vivo somatic cell study or a
second in-vivo germ cell study and specify the need to conduct such studies in mammalian species. Those studies
should be listed together with the mutagenicity concerns they are to address. In addition, the information
requirements on pre-natal developmental toxicity and Extended One-Generation Reproductive Toxicity studies
should be amended to clarify the need for a study in, and the choice of, a second species, as well as the preferred
administration routes for testing and the deviations from the general rules. Furthermore, the reference to a specific
requirement on biotic degradation in point 9.2.1 is no longer necessary and should therefore be deleted, while
(4) Regulation (EC) No 1272/2008 of the European Parliament and of the Council of 16 December 2008 on classification, labelling and
packaging of substances and mixtures, amending and repealing Directives 67/548/EEC and 1999/45/EC, and amending Regulation
(EC) No 1907/2006 (OJ L 353, 31.12.2008, p. 1).
(5) OECD TG 473 and 487.L 98/40 EN Official Journal of the European Union 25.3.2022
relevant specific rules for adaptation in subsection 9.2 should be amended accordingly. Finally, it should be clarified
in subsection 9.4, as well as point 9.5.1 that in addition to degradation products, long-term toxicity testing of
transformation products is required to investigate their effects on terrestrial and sediment organisms.
(11) Regulation (EC) No 1907/2006 should therefore be amended accordingly.
(12) The proposed amendments aim at providing clarifications of certain standard information requirements and specific
rules for their adaptation, as well as at increasing the legal certainty of the evaluation practices already applied by the
Agency. Nevertheless, it cannot be discarded that as a result of the amendments, certain registration dossiers will
need to be updated. The application of this Regulation should therefore be deferred.
(13) The measures provided for in this Regulation are in accordance with the opinion of the Committee established under
Article 133 of Regulation (EC) No 1907/2006,
HAS ADOPTED THIS REGULATION:
Article 1
Annexes VI to X to Regulation (EC) No 1907/2006 are amended in accordance with the Annex to this Regulation.
Article 2
This Regulation shall enter into force on the twentieth day following that of its publication in the Official Journal of the
European Union.
It shall apply from 14 October 2022.
This Regulation shall be binding in its entirety and directly applicable in all Member States.
Done at Brussels, 24 March 2022.
For the Commission
The President
Ursula VON DER LEYEN25.3.2022 EN Official Journal of the European Union L 98/41
ANNEX
Regulation (EC) No 1907/2006 is amended as follows:
(1) Annex VI is amended as follows:
(a) point 1.1.1 is replaced by the following:
‘1.1.1. Name, address, telephone number and email address’;
(b) the following point 1.1.4 is added:
‘1.1.4. Where an only representative has been appointed in accordance with Article 8(1), the following
information regarding the natural or legal person established outside the Union who appointed the only
representative: name, address, telephone number, email address, contact person, location of the
production site(s) or formulation site(s), as appropriate, company website, as appropriate and national
company identification number(s), as appropriate.’;
(c) subsection 1.2 is replaced by the following:
‘1.2. Joint submission of data
Articles 11 and 19 provide for the possibility for the lead registrant to submit parts of the registration
information on behalf of other member registrants.
When, in accordance with Article 11(1), the lead registrant submits information referred to in Article 10,
point (a)(iv), (vi), (vii) and (ix), the lead registrant shall describe the composition(s), nanoform or set of
similar nanoforms to which this information relates in accordance with points 2.3.1 to 2.3.4 and
subsection 2.4 of this Annex. Each member registrant relying on information submitted by the lead
registrant shall indicate which information thus submitted pertains to which composition, nanoform or set
of similar nanoforms of the substance that the registrant identifies in accordance with Article 10, point (a)
(ii), and Article 11(1).
When, in accordance with Article 11(3), a registrant submits information referred to in Article 10, point (a)
(iv), (vi), (vii) or (ix), separately, this registrant shall describe the composition(s), nanoform or set of similar
nanoforms of the substance to which this information relates in accordance with points 2.3.1 to 2.3.4 and
subsection 2.4 of this Annex.’;
(d) point 1.3.1 is replaced by the following:
‘1.3.1. Name, address, telephone number and email address’;
(e) subsection 2.1 is replaced by the following:
‘2.1. Name and any other identifier of each substance’;
(f) point 2.1.1 is replaced by the following:
‘2.1.1. Name(s) in the IUPAC nomenclature. If unavailable, other international chemical name(s)’;
(g) point 2.1.3 is replaced by the following:
‘2.1.3. EC number, i.e. Einecs, Elincs or NLP number, or the number assigned by the Agency (if available and
appropriate)’;
(h) point 2.1.5 is replaced by the following:
‘2.1.5. Other identity code, such as customs number (if available)’;
(i) subsection 2.2 is replaced by the following:
‘2.2. Information related to molecular and structural formula or crystal structure of each substance’;
(j) point 2.2.1 is replaced by the following:
‘2.2.1. Molecular formula and structural formula (including SMILES notation and other representation if
available) and description of crystal structure(s)’;
(k) points 2.3.1 to 2.3.7 are replaced by the following:
‘2.3.1. Degree of purity (%), if applicableL 98/42 EN Official Journal of the European Union 25.3.2022
2.3.2. Names of constituents and impurities
In the case of a substance of unknown or variable composition, complex reaction products or biological
materials (UVCB):
— names of constituents present at a concentration of ≥ 10 %;
— names of known constituents present at a concentration of < 10 %;
— for constituents that cannot be identified individually, description of groups of constituents based on
chemical nature;
— description of the origin or source and the manufacturing process
2.3.3. Typical concentration and concentration range (in percentage) of constituents, groups of constituents that
cannot be identified individually and impurities as specified in point 2.3.2
2.3.4. Names and typical concentration and concentration range (in percentage) of additives
2.3.5. All necessary qualitative analytical data specific for the identification of the substance, such as ultra-violet,
infra-red, nuclear magnetic resonance, mass spectrum or diffraction data
2.3.6. All necessary quantitative analytical data specific for the identification of the substance, such as
chromatographic, titrimetric, elemental analysis or diffraction data
2.3.7. Description of the analytical methods or the appropriate bibliographical references that are necessary for
the identification of the substance (including the identification and quantification of its constituents and,
where appropriate, its impurities and additives). The description shall consist of the experimental
protocols followed and the relevant interpretation of the results reported under points 2.3.1 to 2.3.6. This
information shall be sufficient to allow the methods to be reproduced.’;
(l) point 2.4.6 is replaced by the following:
‘2.4.6. Description of the analytical methods or the appropriate bibliographical references for the information
elements in this subsection (2.4). The description shall consist of the experimental protocols followed and
the relevant interpretation of the results reported under points 2.4.2 to 2.4.5. This information shall be
sufficient to allow the methods to be reproduced.’;
(m) the following subsection 2.5 is added:
‘2.5. Any other available information relevant for the identification of the substance’;
(n) subsection 3.5 is replaced by the following:
‘3.5. General description of the identified use(s)’;
(2) Annex VII is amended as follows:
(a) in subsection 8.4, in column 2, the text is replaced by the following:
‘8.4. In case of a positive 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, the25.3.2022 EN Official Journal of the European Union L 98/43
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 cri
teria 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.’;
(b) in point 8.4.1, in column 2, the text is replaced by the following:
‘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 such case, an in vitro study
referred to in Annex VIII, point 8.4.3, shall be provided.’;
(c) in point 9.1.1, in column 1, the second paragraph is deleted.
(d) in point 9.1.1, in column 2, the text is replaced by the following:
‘9.1.1. The study does not need to be conducted in any of the following cases:
— there are factors indicating that short-term 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,
— a long-term aquatic toxicity study on invertebrates is available.
For nanoforms, the study may not be waived on the basis of high insolubi
lity 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 of the substance,
for instance:
— if the substance is poorly water soluble (solubility below 1 mg/L), or
— for nanoforms with low dissolution rate in the relevant test media.’;L 98/44 EN Official Journal of the European Union 25.3.2022
(e) in point 9.1.2, in column 2, the text is replaced by the following:
‘9.1.2. The study does not need to be conducted if there are 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.’;
(3) Annex VIII is amended as follows:
(a) in subsection 8.4, in column 2, the following text is added:
‘8.4. The studies referred to in points 8.4.2 and 8.4.3 do not need to be conducted
in any of the following cases:
— adequate data from the corresponding in vivo study, (namely in vivo chro
mosomal aberration (or micronucleus) study regarding point 8.4.2 or in
vivo mammalian gene mutation study regarding point 8.4.3), are avail
able,
— the substance is known to cause germ cell mutagenicity, meeting the cri
teria for classification as germ cell mutagen 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.
In case of a positive result in any of the in vitro genotoxicity studies
referred to in Annex VII or this Annex, which gives rise to concern, the
registrant shall propose, or the Agency may require, an appropriate in
vivo study referred to in Annex IX, point 8.4. The in vivo study shall
address the chromosomal aberration concern or the gene mutation con
cern or both as appropriate.
In case an in vitro mutagenicity study referred to in points 8.4.2 or 8.4.3 is
not applicable for the substance, the registrant shall provide a justifica
tion and 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.’;
(b) in point 8.4.2, in column 1, the text is replaced by the following:
‘8.4.2. In vitro mammalian chromosomal aberration study
or in vitro mammalian micronucleus study’;
(c) in point 8.4.2, the text in column 2 is deleted;
(d) in point 8.4.3, the text in column 2 is deleted;
(e) in point 8.6.1, in column 2, the introductory wording of the sixth paragraph is replaced by the following:
‘Further studies shall be proposed by the registrant or may be required by the
Agency in case of:’;25.3.2022 EN Official Journal of the European Union L 98/45
(f) point 8.7.1 is replaced by the following:
‘8.7.1. Screening for reproductive/develop 8.7.1. This study does not need to be conducted in any of the
mental toxicity (OECD TG 421 or following cases:
TG 422); the preferred species is the
— the substance is known to be a genotoxic carcinogen,
rat. The route of administration shall
meeting the criteria for classification both in the hazard
be oral if the substance is a solid or
class germ cell mutagenicity category 1A, 1B or 2 and in
liquid, and inhalation if the substance
the hazard class carcinogenicity category 1A or 1B, and
is a gas; deviations may be made if
appropriate risk management measures are implemen
scientifically justified, for example
ted,
through evidence of equivalent or
higher systemic exposure via another — the substance is known to be a germ cell mutagen, meet
relevant route of human exposure or ing the criteria for classification in the hazard class germ
route-specific toxicity. cell mutagenicity category 1A or 1B and appropriate risk
management measures are implemented,
— relevant human exposure can be excluded in accordance
with Annex XI, Section 3,
— a pre-natal developmental toxicity study (OECD TG 414)
referred to in Annex IX, point 8.7.2 or an Extended One-
Generation Reproductive Toxicity Study (OECD TG 443)
referred to in Annex IX, point 8.7.3 is available or pro
posed by the registrant; or a Two-Generation Reproduc
tive Toxicity Study (OECD TG 416) is available,
— a substance is known to have an adverse effect on sexual
function or fertility, meeting the criteria for classification
in the hazard class reproductive toxicity category 1A or
1B: May damage fertility (H360F), and the available data
are adequate to support a robust risk assessment,
— a substance is known to cause developmental toxicity,
meeting the criteria for classification in the hazard class
reproductive toxicity category 1A or 1B: May damage the
unborn child (H360D), and the available data are ade
quate to support a robust risk assessment.
In case of serious concerns about potential adverse
effects on sexual function, fertility or development, the
registrant shall propose, or the Agency may require
either an Extended One-Generation Reproductive Toxi
city Study (OECD TG 443), referred to in Annex IX, point
8.7.3, or a pre-natal developmental toxicity study (OECD
TG 414), referred to in Annex IX, point 8.7.2, instead of
the screening study (OECD TG 421 or 422) to address
those concerns. Those serious concerns include among
others:
— adverse effects related to sexual function, fertility or
development based on available information, not meet
ing the criteria for classification as reproductive toxicity
category 1A or 1B,
— possible developmental or reproductive toxicity of the
substance predicted from information on structurally
related substances, (Q)SAR estimates or in vitro meth
ods.’;L 98/46 EN Official Journal of the European Union 25.3.2022
(g) in point 8.8.1, in column 2, the first paragraph is replaced by the following:
‘For nanoforms without high dissolution rate in biological media a
toxicokinetics study shall be proposed by the registrant or may be
required by the Agency in case such an assessment cannot be
performed on the basis of relevant available information,
including from the study conducted in accordance with 8.6.1’;
(h) the following subsection 9.1 is inserted:
‘9.1. Aquatic toxicity 9.1. Long-term aquatic toxicity testing referred to in Annex IX,
subsection 9.1, in addition to short-term toxicity testing shall
be proposed by the registrant or may be required by the
Agency if the chemical safety assessment performed in
accordance with Annex I indicates that it is needed to further
investigate the effects on aquatic organisms, for example when
further information is needed for the refinement of the PNEC
or if additional toxicity information as set out in Annex XIII,
point 3.2.3, would be necessary to assess PBT or vPvB
properties of the substance.
The choice of the appropriate test(s) shall be made on the basis
of the results of the chemical safety assessment.’;
(i) point 9.1.3 is replaced by the following:
‘9.1.3. Short-term toxicity testing on fish 9.1.3. The study does not need to be conducted in any of the
following cases:
— there are factors indicating that short-term aquatic toxi
city is unlikely to 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 fish 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 fish referred to in Annex
IX, point 9.1.6, 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 of the substance, for
instance:
— if the substance is poorly water soluble (below 1 mg/L),
or
— for nanoforms with low dissolution rate in the relevant
test media.’;25.3.2022 EN Official Journal of the European Union L 98/47
(j) in subsection 9.2, in column 2, the text is replaced by the following:
‘9.2. Further information on degradation shall be generated or
further degradation testing as described in Annex IX shall be
proposed if the chemical safety assessment performed in
accordance with Annex I indicates that it is needed to
further investigate the degradation of the substance. That
could for example be the case if additional information on
degradation as set out in Annex XIII, point 3.2.1, is required
to assess PBT or vPvB properties of the substance in
accordance with subsection 2.1 of that Annex.
For nanoforms that are not soluble, nor have high dissolution
rate, such test(s) shall consider morphological transformation
(e.g. irreversible changes in particle size, shape and surface
properties, loss of coating), chemical transformation (e.g.
oxidation, reduction) and other abiotic degradation (e.g.
photolysis).
The choice of the appropriate test(s) shall be made on the
basis of the results of the chemical safety assessment.
In case the generation of additional information requires
further testing in accordance with Annex IX, the registrant
shall propose or the Agency may require such testing.’;
(k) in subpoint 9.2.2.1, in column 2, the text is replaced by the following:
‘9.2.2.1. The study does not need to be conducted in any of the
following cases:
— the substance is readily biodegradable,
— the substance is highly insoluble in water,
— based on the structure, the substance does not have
chemical groups that can hydrolyse.
For nanoforms, the study may not be waived on the basis
of high insolubility in water alone.’;
(l) in subsection 9.3, in column 2, the following text is added:
‘9.3. Further information on bioaccumulation shall be generated if
additional information on bioaccumulation as set out in
Annex XIII, point 3.2.2, is required to assess PBT or vPvB
properties of the substance in accordance with subsection
2.1 of that Annex.
In case the generation of additional information requires
further testing in accordance with Annex IX or Annex X, the
registrant shall propose or the Agency may require such
testing.’;
(4) Annex IX is amended as follows:
(a) in point 7.16, the second bullet point in column 2 is deleted;L 98/48 EN Official Journal of the European Union 25.3.2022
(b) subsection 8.4 is replaced by the following:
‘8.4. Mutagenicity 8.4. The studies referred to in points 8.4.4 and 8.4.5 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 appropri
ate 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 implemen
ted.’;
(c) the following points 8.4.4 and 8.4.5 are added:
‘8.4.4. An appropriate in vivo mammalian somatic cell gen 8.4.4. The in vivo mammalian somatic cell genotoxi
otoxicity study, if there is a positive result in any of city study does not need to be conducted if
the in vitro genotoxicity studies referred to in Annex there are adequate results available from an
VII or Annex VIII, which gives rise to concern. The in appropriate in vivo mammalian somatic cell
vivo mammalian somatic cell genotoxicity study genotoxicity study.
shall address the chromosomal aberration concern
or the gene mutation concern or both, as appropri
ate.
8.4.5. An appropriate in vivo mammalian germ cell geno 8.4.5. The study does not need to be conducted if
toxicity study, if there is a positive result in an avail there is clear evidence that neither the sub
able in vivo mammalian somatic cell genotoxicity stance nor its metabolites reach the germ
study, which gives rise to concern. The in vivo mam cells.’;
malian germ cell genotoxicity study shall address the
chromosomal aberration concern or the gene muta
tion concern or both, as appropriate.
(d) point 8.7.2 is replaced by the following:
‘8.7.2. Pre-natal developmental toxicity study (OECD TG 8.7.2. An additional pre-natal developmental toxi
414) on one species; the preferred species is the rat city study in a second species, that is the other
or the rabbit. The route of administration shall be preferred species to the one used in the first
oral if the substance is a solid or liquid, and inhala study, shall be proposed by the registrant or
tion if the substance is a gas; deviations may be made may be required by the Agency if there is a
if scientifically justified, for example through evi concern for developmental toxicity based on
dence of equivalent or higher systemic exposure the outcome of the first study and all other
via another relevant route of human exposure or relevant data. That could be the case for ex
route-specific toxicity. ample if the study on the first species shows
developmental toxicity not meeting the cri
teria for classification in the hazard class re
productive toxicity category 1A or 1B; May
damage the unborn child (H360D). Devia
tions from the default route of administration
and deviations in the choice of species shall
be scientifically justified.’;25.3.2022 EN Official Journal of the European Union L 98/49
(e) in point 8.7.3, in column 1, the text is replaced by the following:
‘8.7.3. Extended One-Generation Reproductive Toxicity
Study (OECD TG 443), basic test design (cohorts
1A and 1B without extension to include an F2 gen
eration), one species, if the available repeated dose
toxicity studies (e.g. 28-day or 90-day studies, or
OECD TG 421 or 422 screening studies) indicate
adverse effects on reproductive organs or tissues or
reveal other concerns in relation with reproductive
toxicity. The route of administration shall be oral if
the substance is a solid or liquid, and inhalation if the
substance is a gas; deviations may be made if scien
tifically justified, for example through evidence of
equivalent or higher systemic exposure via another
relevant route of human exposure or route-specific
toxicity.’;
(f) in point 8.7.3, in column 2, the introductory wording of the first paragraph is replaced by the following:
‘8.7.3. An Extended One-Generation Reproductive Toxicity Study
with the extension of cohort 1B to include the F2 generation
shall be proposed by the registrant or may be required by the
Agency if:’;
(g) in point 8.7.3, in column 2, the introductory wording of the second paragraph is replaced by the following:
‘An Extended One-Generation Reproductive Toxicity Study
including cohorts 2A/2B (developmental neurotoxicity) and/or
cohort 3 (developmental immunotoxicity) shall be proposed by
the registrant or may be required by the Agency in case of
particular concerns on (developmental) neurotoxicity or
(developmental) immunotoxicity justified by any of the following:’;
(h) in subsection 9.1, in column 2, the text is replaced by the following:
‘9.1. Long-term toxicity testing other than the tests referred to in
points 9.1.5 and 9.1.6 shall be proposed by the registrant or
may be required by the Agency if the chemical safety
assessment performed in accordance with Annex I indicates
that it is needed to further investigate the effects of the
substance on aquatic organisms.
The choice of the test(s) shall be made on the basis of the
results of the chemical safety assessment.’;
(i) point 9.1.6 is replaced by the following:
‘9.1.6. Long-term toxicity testing on fish, (unless already 9.1.6. Fish short-term toxicity tests on embryo and
provided as part of Annex VIII requirements). sac-fry stages (OECD TG 212) that were in
itiated before 14 April 2022shall be consid
ered appropriate to address this standard inL 98/50 EN Official Journal of the European Union 25.3.2022
The information shall be provided for subpoint 9.1.6.1 or formation requirement provided that the
subpoint 9.1.6.3. substance is not highly lipophilic (log Kow
> 4) or there is no indication of endocrine
disrupting properties or any other specific
mode of action.’;
(j) subpoint 9.1.6.1 is replaced by the following:
‘9.1.6.1. Fish early-life stage (FELS) toxicity test (OECD TG
210)’;
(k) subpoint 9.1.6.2 is deleted.
(l) subpoint 9.1.6.3 is replaced by the following:
‘9.1.6.3. Fish juvenile growth test (OECD TG 215)’;
(m) in subsection 9.2, in column 2, the text is replaced by the following:
‘9.2. Further degradation testing shall be proposed by the registrant
or may be required by the Agency if the chemical safety
assessment performed in accordance with Annex I indicates
that it is needed to further investigate the degradation of the
substance and its transformation or degradation products.
The choice of the appropriate test(s) and test media shall be
made on the basis of the results of the chemical safety
assessment.’;
(n) in point 9.2.3, in column 1, the text is replaced by the following:
‘9.2.3. Identification of transformation and abiotic and bio
tic degradation products’;
(o) in subsection 9.4, in column 2, the text is replaced by the following:
‘9.4. These studies do not need to be conducted if direct and
indirect exposure of the soil compartment is unlikely.
In the absence of toxicity data for soil organisms, the
equilibrium partitioning method may be applied to assess
the hazard to soil organisms. Where the equilibrium
partitioning method is applied to nanoforms, this shall be
scientifically justified. The choice of the appropriate test(s)
shall be made on the basis of the results of the chemical
safety assessment.
In particular for substances that have a high potential to
adsorb to soil or that are very persistent, the registrant shall
propose or the Agency may require long-term toxicity testing
as referred to in Annex X instead of short-term toxicity
testing.’;25.3.2022 EN Official Journal of the European Union L 98/51
(5) Annex X is amended as follows:
(a) subsection 8.4. is replaced by the following:
‘8.4. Mutagenicity 8.4. The studies referred to in points 8.4.6 and 8.4.7 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 appropri
ate 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 or 1B or 2 and
in the hazard class carcinogenicity category 1A or 1B, and
appropriate risk management measures are implemen
ted.’;
(b) the following points 8.4.6 and 8.4.7 are added:
‘8.4.6. A second in vivo mammalian somatic cell genotoxi
city study, if there is a positive result in any of the in
vitro genotoxicity studies referred to in Annex VII or
Annex VIII, which gives rise to both chromosomal
aberration concern and gene mutation concern. The
second study shall address chromosomal aberration
or gene mutation, as appropriate, which has not
been addressed by the first in vivo mammalian so
matic cell genotoxicity study.
8.4.7. A second in vivo mammalian germ cell genotoxicity 8.4.7. The study does not need to be conducted if
study, if there is a positive result in in vivo mamma there is clear evidence that neither the sub
lian somatic cell genotoxicity studies, which gives stance nor its metabolites reach the germ
rise to both chromosomal aberration concern and cells.’;
gene mutation concern. The second study shall ad
dress the chromosomal aberration or gene mutation,
as appropriate, which has not been addressed by the
first in vivo mammalian germ cell genotoxicity study.
(c) point 8.7.2 is replaced by the following:
‘8.7.2. Pre-natal developmental toxicity study (OECD TG Deviations from the default route of administration
414) in a second species, the preferred species is and deviations in the choice of species shall be
the rat or the rabbit, whichever was not used in the scientifically justified.’;
first study under Annex IX. The route of administra
tion shall be oral if the substance is a solid or liquid,
and inhalation if the substance is a gas; deviations
may be made if scientifically justified, for example
through evidence of equivalent or higher systemic
exposure via another relevant route of human expo
sure or route-specific toxicity.L 98/52 EN Official Journal of the European Union 25.3.2022
(d) in point 8.7.3, in column 1, the text is replaced by the following:
‘8.7.3. Extended One-Generation Reproductive Toxicity
Study (OECD TG 443), basic test design (cohorts
1A and 1B without extension to include an F2 gen
eration), one species, unless already provided as part
of Annex IX requirements. The route of administra
tion shall be oral if the substance is a solid or liquid,
and inhalation if the substance is a gas; deviations
may be made if scientifically justified, for example
through evidence of equivalent or higher systemic
exposure via another relevant route of human expo
sure or route-specific toxicity.’;
(e) in point 8.7.3, in column 2, the introductory wording of the first paragraph is replaced by the following:
‘An Extended One-Generation Reproductive Toxicity Study with the
extension of cohort 1B to include the F2 generation shall be
proposed by the registrant or may be required by the Agency if:’;
(f) in point 8.7.3, in column 2, the introductory wording of the second paragraph is replaced by the following:
‘An Extended One-Generation Reproductive Toxicity Study
including cohorts 2A/2B (developmental neurotoxicity) and/or
cohort 3 (developmental immunotoxicity) shall be proposed by the
registrant or may be required by the Agency in case of particular
concerns on (developmental) neurotoxicity or (developmental)
immunotoxicity justified by any of the following:’;
(g) in subsection 9.2, in column 2, the text is replaced by the following:
‘9.2. Further degradation testing shall be proposed by the registrant
or may be required by the Agency, if the chemical safety
assessment performed in accordance with Annex I indicates
that it is needed to further investigate the degradation of the
substance and its transformation and degradation products.
The choice of the appropriate test(s) and test media shall be
made on the basis of the results of the chemical safety
assessment.’;
(h) point 9.2.1 is deleted;
(i) in subsection 9.4, in column 2, the text is replaced by the following:
‘9.4. Long-term toxicity testing shall be proposed by the registrant
or may be required by the Agency if the results of the chemical
safety assessment performed in accordance with Annex I
indicates that it is needed to further investigate the effects of
the substance or of transformation and degradation products
on terrestrial organisms. The choice of the appropriate test(s)
shall be made on the basis of the outcome of the chemical
safety assessment.25.3.2022 EN Official Journal of the European Union L 98/53
These studies do not need to be conducted if direct and indirect
exposure of the soil compartment is unlikely.’;
(j) in point 9.5.1, in column 2, the text is replaced by the following:
‘9.5.1. Long-term toxicity testing shall be proposed by the registrant
or may be required by the Agency if the results of the
chemical safety assessment performed in accordance with
Annex I indicates that it is needed to further investigate the
effects of the substance or of relevant transformation and
degradation products on sediment organisms.
The choice of the appropriate test(s) shall be made on the
basis of the results of the chemical safety assessment.’.