1 
 EN 
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 e -mail 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, e -mail 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 to submit  parts of the registration information  by 
a lead registrant on behalf of other 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 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).  
Whe n, 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 whi ch 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 e -mail address’;  
 
(e) subsection 2.1 is replaced by the fol lowing:  
‘2.1. Name and any other identifier of each substance’;  
 
(f) point 2.1.1 is replaced by the following:  2 
 ‘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 or other 
representation if available) and description of crystal structure(s)’ ; 
 
(k) point s 2.3.1  to 2.3.7  are replaced by the following:  
‘2.3.1.  Degree of purity (%), if applicable  
 
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 t hat 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.  Concentration (in percentage) of constituents, groups of constituents that cann ot be 
identified individually and impurities as specified in point 2.3.2  
 
2.3.4.  Names and order of magnitude 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  
 3 
 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.  Descript ion 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 r eplaced 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 relev ant 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 identi fication 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 tho se 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 4 
 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 
carried out 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 mutagen icity 
category 1A or 1B, and appropriate 
risk management measures are 
implemented , 
- the substance is known to be a 
geno toxic 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, 5 
 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 
invertebrate s 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 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. ’; 
 
 
 
 
(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:  
 6 
 (a) in subsection 8.4, in column 2 , the following text is added : 
  ‘8.4. The studies  referred to  in 
point s 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  chromosomal 
aberration  (or micronucleus)  
study  regarding point  8.4.2 or in 
vivo mammalian gene mutation 
study  regarding point  8.4.3 ), are 
available,  
- the substance is known to cause 
germ cell mutagenicity, meeting 
the criteria 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, meet ing 
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 an y 
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 concern or both  as 
appropriate .’; 7 
  
(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: ‘;  
 
(f) point 8.7.1  is replaced by the following:  
 ‘8.7.1 Screening for reproductive/ 
developmental toxicity (OECD TG 
421 or TG 422) ; the preferred species 
is the rat. 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  scientifically justified, for 
example  through evidence of 
equivalent or highe r systemic 
exposure via another relevant route 
of human exposure or route -specific 
toxicity.  8.7.1 This study does not need 
to be conducted in any of the 
following cases :  
- the substance is known to be a 
genotoxic carcinogen, meeting 
the criteria for clas sification  
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,  
- the substance is known to be a 
germ cell mutagen, meeti ng the 
criteria for classification in the 
hazard class germ cell 
mutagenicity category 1A or 1B 
and appropriate risk 
management measures are 
implemented,  8 
 - relevant human exposure can 
be excluded  in accordance with 
Annex XI, Section 3,  
- a pre -natal devel opmental 
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 proposed  by 
the registrant ; or a Two-
Generation Reproductive 
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 fertilit y (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 th e unborn child 
(H360D), and the available data 
are adequate 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 
Toxicity Study, referred to in 
Annex IX, point 8.7.3, or a pre -
natal developmental toxicity 9 
 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 meeting the 
criteria for classification as 
reproductive toxicity category 
1A o r 1B,  
- possible developmental or 
reproductive toxicity of the 
substance predicted from 
information on structurally 
related substances, (Q)SAR 
estimates or in vitro  methods .’; 
 
(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 s ubsection  9.1 is inserted : 
 
‘ 9.1. Aquatic toxicity’  9.1. Long -term aquatic toxicity testing  
referred to in Annex IX , point 9.1.6 , 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 accord ance 10 
 with Annex I indicates th at it is needed to 
further investigate the effects on aquatic 
organisms, for example when further 
information is needed for the refinement of 
the PNEC.  
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 follow ing: 
 
 ‘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 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 fish 
is available.  
For nanoforms, the study may not be 
waived on the basis of high insolubility in 
water alone.  
The r egistrant 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. ’; 
 
(j)  in subsection 9.2,  in column 2 , the text  is replaced by the following:  11 
   ‘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 accord ance with  to Annex I 
indicates that it is  need ed 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. oxidatio n, 
reduction) and other abiotic degradation (e.g. 
photolysis).  
The choice of the appropriate test(s) will 
depend on the results of the chemical safety 
assessment.  
In case the generation of additional 
information require s further testing in 
accord ance 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 followimg 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.’;  12 
  
(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 in 
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 require s further testing in 
accord ance 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) subsection 8.4. is replaced by the following :  
 
‘8.4. 
Mutagenicity’   8.4. The studies  referred to  in point s 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 mutagen icity 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 ha zard class carcinogenicity category 
1A or 1B, and appropriate risk management measures 
are implemented.’ ; 
 
 
 
(b) the followi ng point s 8.4. and  8.4. 5 are added:  13 
  
 
 
 
 
 
 
 
(c) point 8.7.2   is replaced by the following:  
 ‘8.7.2 Pre-natal developmental 
toxicity study (OECD TG 414) on 
one species ; the preferred species is 
the rat or the rabbit. 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  
scientifically justified, for example   
through evidence of  equivalent or 
higher systemic exposure via another 
relevant route of human exposure  or 
route -specific toxicity.  8.7.2. An additional pre -natal 
developmental toxicity study in 
a second species, that is  another 
species  than used in the first 
study shall be proposed by the 
registrant or may be required by 
the Agency if there is a concern 
for developmental toxicity 
based on the outcome of the 
first study and all other relevant 
data. That could be the case for 
example if the study on the first 
species shows developmental 
toxicity not meeting the criteria 
for classification in the hazard 
class reproductive toxicity 
category 1A or 1B; May 
damage the unborn child 
(H360D). The route of 
administration shall be  oral if  ‘8.4.4. An appropriate in vivo  
mammalian  somatic cell genotoxicity 
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 concern . The 
in vivo mammalian somatic cell 
genotoxicity study shall  address  the 
chromosomal aberration concern or 
the gene mutation concern or both , as 
appropriate . 
8.4.5. An appropriate in vivo  
mammalian germ cell genotoxicity 
study, if there is a positive result in an 
available in vivo  mammalian somatic 
cell genotoxicity study, which gives 
rise to concern. The in vivo  
mammal ian germ cell genotoxicity 
study shall address the chromosomal 
aberration concern or the gene 
mutation concern or both, as 
appropriate.  8.4.4. The in vivo  mammalian 
somatic cell genotoxicity study   
does not need to be conducted if 
there are adequate  results 
available from an appropriate in 
vivo mammalian somatic cell 
genotoxicity study.  
 
 
 
8.4.5. The study does not need 
to be conducted if there is clear 
evidence that neither the 
substance nor its metabolites 
reach the germ cells.’;  14 
 the substance is a solid or liquid, 
and inhalation route if the 
substance is a gas; deviations 
may be  made if  scientifically 
justified, for example  by 
reference to higher systemic 
exposure. If the first study was 
performed on rat, the second 
study shall  be performed on 
rabbit and vice versa; deviations 
in the choice of species shall  be 
scientifically justified. ’; 
 
(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 a n F2 generation), one 
species, if the avai lable 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 administr ation 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 exposure or 
route -specific toxicity.’;   
 
(e) in point 8.7.3,  in column 2, the introductory word ing 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 15 
 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 9.1, 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  need ed 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.’;  
 
(h) point 9.1.6 is replaced by the following:  
‘9.1.6. Long -term 
toxicity testing on fish, 
(unless already provided 
as part of Annex VIII 
requirements).  
The information shall be 
provided for subpoint 
9.1.6.1 or subpoint 
9.1.6.3.  9.1.6. Fish short -term toxicity tests on 
embryo and sac -fry stages (OECD TG 212) 
that were initiated before … [OP, please 
insert the date of entry into force of this 
amending Regulation ] shall be considered 
appropriate to address this standard 
information requirement provided that  there 
is no indication of endocrine disrupting 
properties.’;  16 
  
 
 
 
(i) subpoint 9.1.6 .1 is replaced by the following:  
‘9.1.6.1. Fish early -life 
stage (FELS) toxicity test  
(OECD TG 210) ’;  
 
(j) subpoint 9.1.6.2 is deleted.  
 
(k) subpoint 9.1.6.3 is replaced by the following:  
‘9.1.6.3. Fish juvenile 
growth test  
(OECD TG 215) ’;  
 
 
(l)  in subse ction 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 accord ance 
with Annex I indicates that it is  need ed 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. ’; 
 
 
(m)  in point 9.2.3, in column 1 , the text  is replaced by the following:  
‘9.2.3. Identification of 
transformation and degradation 
products’ ;  
 
(n) in subsection 9.4, in column 2 , the text  is replaced by the following:  17 
  ‘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 outcome 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 .’; 
 
 
(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 carried out 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 
mutagen icity category 1A or 1B, 
and appropriate risk 
management measures are 
implemented,  
- the substance is known to be a 
genot oxic 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 18 
 management measures are 
implemented.’;  
 
 
 
(b) the followi ng point s 8.4.6 and 8.4. 7 are added:  
 ‘8.4.6. A second in vivo  mammalian 
somatic cell genotoxicity 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  
addre ss chromosomal aberration or 
gene mutation , as appropriate , which 
has not been addressed by the first in 
vivo mammalian somatic cell 
genotoxicity study.   
 
 
 8.4.7. A second in vivo mammalian 
germ cell genotoxicity study, if there 
is a positive result  in in vivo  
mammalian somatic cell genotoxicity 
studies , which gives rise to both 
chromosomal aberration  concern and 
gene mutation concern.  The second 
study shall address the chromosomal 
aberration or gene mutation , as 
appropriate , which has not been 
addressed by the first in vivo  
mammalian germ cell genotoxicity 
study.  8.4.7. The study does not need to 
be conducted if there is clear 
evidence that neither the 
substance nor its metabolites 
reach the germ cells.’ ; 
 
(c) point 8.7.2 is replaced by the following:  
 
 ‘8.7.2. Pre-natal developmental 
toxicity study (OECD TG 414) in a 
second species , that is  another 
species than used in the first study.  19 
 The route of adminis tration 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 exposure or 
route -specific toxicity. If the first 
study was performed on rat , the 
second study shall  be performed on 
rabbit and vice versa; deviations in 
the choice of species shall  be 
scientifically justified. ’; 
 
(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 a n F2 
generation), one species, unless 
already provided as part of Annex 
IX requirements. 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  
scientifically justified, for example  
through evidence of equivalent or 
higher systemic expos ure via another 
relevant  route of human exposure 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: ’; 
 20 
 (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 req uired 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 accord ance 
with Annex I indicates  that it is  need ed 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  
accord ance with  Annex I indicates  that it is  
need ed to further investigate the effects of 
the substance or of transformation and 
degradation products on terrestrial 
organisms. The choice of the appropriate 21 
 test(s) shall be made  on the basis of the 
outcome of the chemical  safety assessment.  
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  need ed 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.’ .