1 
 EN 
ANNEX  
Regulation (EC) No 1907/2006 is amended as follows : 
(1) Annex VII is amended as follows:  
 
 (a) in the introductory part, the following paragraph  is inserted  after the sixth  paragraph:  
 
‘Where a test method offers flexibility in the study design, for example  in relation to 
the choice of dose levels, the chosen study design shall  ensure that the data generated 
are adequate for hazard identification and risk assessment.’ ;  
 
 (b) in subsection 7.6 ,  in column 1 , the text is replaced by the following:  
 ‘7.6. Surface tension of an aqueous 
solution ’;  
(c) in subsection 7.7 , in column 2 , the following paragraph  is added:  
  ‘For metals and sparingly 
soluble metal compounds, 
information on transformation 
dissolution in aqueous media 
shall be provided.’ ; 
(d) in point  8.2.1 , in column 2 , the text is replaced by the following:  
  ‘8.2.1. If results from a first in 
vitro study do not allow a 
conclusive decision on the 
classification of a substance or 
on the absence of eye irritation 
potential, (an)other in vitro 
study/ studies for this endpoint 
shall be performed by the 
registrant or may be required  by 
the Agency in accordance with 
Article 41 .’. 
 
 
(2) Annex VIII is amen ded as follows:  
(a)  in the introductory part, the following paragraph  is inserted  after the fourth  paragraph:  
‘Where a test method offers flexibility in the study design, for example  in relation to 
the choice of dose levels, the chosen study  design shall  ensure that the data generated 
are adequate for hazard identification and risk assessment.’ ;   
2 
  
(b) in subsection 8.1 , in column 2 , the first paragraph  is replaced by the following:  
  ‘8.1. An in vivo study for skin 
corrosion/irritation shall be 
conducted  only if the in vitro 
study/ studies under points 8.1.1 
and/or 8.1.2 of Annex VII is (are) 
not applicable, or the results of 
this/these study/ studies is/are not 
adequate for classification and 
risk assessment.’ ; 
(c) in subsection 8.2 , in column 2 , the first paragraph  is replaced by the following:  
  ‘8.2 An in vivo study for serious 
eye damage/ eye irritation  shall 
be conducted  only if the in vitro 
study /stud ies) under point 8.2.1 
of Annex VII is/are not 
applicable, or the results of 
this/these study /stud ies) are not 
adequate for classification and 
risk assessment.’ ; 
(d)   in point  8.6.1 , in column 2 , in the first paragraph , the first indent  is replaced by the 
following:  
  ‘- a reliable sub -chronic (90 
days) or chronic toxicity study is 
available or proposed by the 
registrant , provided that an 
appropriate species, dosage, 
solvent and route of 
administration were used, or’ ; 
 
(e) in point  8.6.1 , in column 2 , the fourth  and fifth paragraph s are replaced by the 
following:  
  ‘For nanoforms without high 
dissolution rate in biological 
media, the study shall include 
toxicokinetic investigations on, 
among others,  the recovery 
period and, where relevant, lung 
clearance . Toxicokinetic 
investigations do not need to be 
performed if  equivalent  
toxicokinetic information on the 
nanoform is already available.  
  
3 
 The sub -chronic toxicity study 
(90 days) (Annex IX, point 8.6.2) 
shall be proposed by the 
registrant , or may be required by 
the Agency in accordance with 
Article 40 or Article 41  if:  
the frequency and duration of 
human exposure indicates that a 
longer term study is appropriate;  
and one of the following 
conditions is met:  
 — other available data indicate 
that the substance may have 
a dangerous property that 
cannot be detected 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 .’; 
 
 
 
(f) in point  9.3.1 , in column 2 , the following paragraph  is inserted after the first 
paragraph:  
   ‘The study may not be waived on 
the basis of low octanol water 
partition coefficient alone, unless  
the adsorptive properties of the 
substance are solely driven by 
lipophilicity . For instance , the 
study may not be waived  if the 
substance is surface active or 
ionisable at environmental pH 
(pH 4 – 9).’. 
 
 
  
4 
 (3) Annex IX is amended as follows:  
 
 (a) in the introductory part, the following paragraph  is inserted  after the fifth paragraph:  
‘Where a test method offers flexibility in the study design, for example  in relation to 
the choice of dose levels, the chosen study  design shall  ensure that the data g enerated 
are adequate for hazard identification and risk assessment.’ ;  
 
(b) in subsection 7.16 , in column 2, the following indent  is added:  
  ‘- or based on the structure, the 
substance does not have any 
chemical group that can 
dissociate .’; 
(c) in subsection 7.17 , in column 2, the following text is added:  
  ‘For hydrocarbon substances the 
kinematic viscosity shall be 
determined at 40°C.’ ; 
(d) point  8.6.1 is deleted ; 
(e) in point  8.6.2 , in column 2 , in the first paragraph , the introductory sentence and  the 
first and second indent s are replaced by the following:  
  ‘8.6.2. The sub -chronic toxicity 
study (90 days) does not need to 
be conducted if:  
— a reliable short -term toxicity 
study (28 days) is available 
showing severe toxicity effects 
meeting the criteria for 
classifying the substance as 
STOT RE Category 1 or 2 , for 
which the observed NOAEL -28 
days, with the application of an 
appropriate uncertainty factor, 
allows the extrapolation towards 
the NOAEL -90 days for the 
same route of exposure, or  
— a reliable chronic toxicity 
study is available or proposed by 
the registrant, provided that an 
appropriate species and route of 
administration were used, or’ ; 
 
  
(f) in point  8.6.2 , in column 2 , the  fourth  paragraph is replaced by the following:   
5 
   ‘For nanoforms without high 
dissolution rate in biological 
media, the study shall include 
toxicokinetic investigations on, 
among others,  the recovery 
period and, where relevant, lung 
clearance . Toxicokinetic 
investigations do not need to be 
performed if  equivalent  
toxicokinetic information on the 
nanoform is already available.’   
(g) in subsection 8.7 , in column 2 , the text is replaced by the following:  
  ‘8.7. The studies do not need to 
be conducted if:  
- the substance is known to 
be a genotoxic 
carcinogen, meeting the 
criteria for classification 
both in the hazard class 
germ cell mutagenicity 
category 2, 1A or 1B and 
carcinogenicity category 
1A or 1B,  and 
appropriate risk 
management measures 
are implement ed, or  
 
- the substance is known to 
be a germ cell mutagen, 
meeting the criteria for 
classification in the 
hazard class germ cell 
mutagenicity category 1A 
or 1B and appropriate risk 
management measures 
are implemented, or  
 
- the substance is of low 
toxicolog ical activity (a 
comprehensive and 
informative dataset 
showing no toxicity in 
any of the tests available), 
it can be proven from 
toxicokinetic data that no 
systemic absorption 
occurs via relevant routes  
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 of exposure (e.g. 
plasma/blood 
concentrations below 
detection limit using a 
sensitive method and 
absence of the substance 
and of metabolites of the 
substance in urine, bile or 
exhaled air) and there is 
no or no significant 
human exposure.  
If a substance is known to have 
an adverse effect on sexual 
function and  fertility, meeting 
the criteria for classification in 
the hazard class reproducti ve 
toxicity  category 1A or 1B: May 
damage fertility (H360F), and 
the available data are adequate to 
support a robust risk assessment, 
then no further testing for sexual 
function and fertility shall  be 
necessary.  
If a substance is known to cause 
developmental toxicity,  meeting 
the criteria for classification in 
the hazard class reproducti ve 
toxicity 1A or 1B: May damage 
the unborn child (H360D), and 
the available data are adequate to 
support a robust risk assessment, 
then no further testing for 
developmental toxicity shall  be 
necessary.’  
 (h) in point  9.3.2 , in column 2 , the following paragraph  is inserted  after the first 
paragraph:  
  ‘The study may not be waived 
on the basis of low octanol water 
partition coefficient alone, 
unless  the potential for 
bioaccumulation of the 
substance is solely driven by 
lipophilicity . For instance , the 
study m ay not be waived  if the 
substance is surface active or 
ionisa ble at environmental pH 
(pH 4 – 9).’;  
7 
 (i) in point  9.3.3 , in column 2 , the following paragraph  is inserted  after the first 
paragraph:  
  ‘The study may not be waived 
on the basis of low octanol water 
partition coefficient alone, 
unless  the adsorptive properties   
of the substance are solely 
driven by lipo philicity . For 
instance , the study may not be 
waived  if the substance is 
surface active or ionisable at 
environmental pH (pH 4 – 9).’ 
 
(4) Annex X is amended as follows:  
 
 (a) in the introductory part, the following paragraph  is inserted  after the fifth paragraph:  
‘Where a test method offers flexibility in the study design, for example  in relation to 
the choice of dose levels, the chosen study  design shall  ensure that the data generated 
are adequate for hazard identification and risk assessment.’ ;   
 
(b) in subsection 8.7 , in column 2, the  text is replaced by the following:  
  
 ‘8.7. The studies do not need to 
be conducted if:  
- the substance is known to 
be a genotoxic 
carcinogen, meeting the 
criteria for classification 
both in the hazard class 
germ cell mutagenicity 
category 2, 1A or 1B and 
carcinogenicity category 
1A or 1B, and appropriate 
risk management 
measures are 
implemente d, or  
 
- the substance is known to 
be a germ cell mutagen, 
meeting the criteria for 
classification in the 
hazard class germ cell 
mutagenicity category 
1A or 1B and appropriate 
risk management  
8 
 measures are 
implemented, or  
 
- the substance is of low 
toxicologi cal activity (a 
comprehensive and 
informative dataset 
showing no toxicity seen 
in any of the tests 
available), it can be 
proven from 
toxicokinetic data that no 
systemic absorption 
occurs via relevant routes 
of exposure (e.g. 
plasma/blood 
concentrations bel ow 
detection limit using a 
sensitive method and 
absence of the substance 
and of metabolites of the 
substance in urine, bile or 
exhaled air) and there is 
no or no significant 
human exposure.  
If a substance is known to have 
an adverse effect on sexual 
funct ion and fertility, meeting 
the criteria for classification in 
the hazard class reproducti ve 
toxicity  category 1A or 1B: May 
damage fertility (H360F), and 
the available data are adequate 
to support a robust risk 
assessment, then no further 
testing for sexua l function and 
fertility shall  be necessary.  
If a substance is known to cause 
developmental toxicity, meeting 
the criteria for classification in 
the hazard class reproducti ve 
toxicity  category 1A or 1B: May 
damage the unborn child 
(H360D), and the available data 
are adequate to support a robust 
risk assessment, then no further 
testing for developmental 
toxicity shall  be necessary.’ .  
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(5) Annex XI is amended as follows:   
 
(a) section 1 (“TESTING DOES NOT APPEAR SCIENTIFICALLY N ECESSARY ”) is 
amended as follows:  
(i) under the header of subsection  1.1. (“Use of existing data ”), the following text is added:  
‘Any data generated as from 1 June 2008 shall not be considered as existing data and shall  not 
be subject to the general rules for adaptation laid down  in this point  (1.1).’ ; 
 
(ii) the header  of point  1.1.1. is replaced by the following:  
‘1.1.1. Data on ph ysical -chemical properties from experiments not carried out according to the 
test methods referred to in Article 13(3)’ ; 
 
(iii) in subsection  1.2. (“Weight of evidence ”), the text  is replaced by the following:  
‘There is sufficient weight of evidence when i nformation from several independent sources 
together enable, through a reasoned justification, a conclusion on the information requirement, 
while the information from each single source alone is insufficient to fulfil the information 
requirement. The justi fication must have regard to the information that would otherwise be 
obtained from the study that shall normally be performed for this information requirement.  
There may also be sufficient weight of evidence from the use of newly developed test methods, 
not yet included in the test methods referred to in Article 13(3), leading to a reasoned 
justification that they provide the information that would enable a conclusion on the 
information requirement.  
Weight of evidence may lead to the conclusion that a subs tance has or has not a particular 
property.  
If there is sufficient weight of evidence, the information requirement is fulfilled. Consequently, 
further testing on vertebrate animals shall be omitted and further testing not involving 
vertebrate animals may b e omitted.  
In all cases , the information provided shall be adequate for the purpose of classification, 
labelling and/or risk assessment, and adequate and reliable documentation shall be provided, 
including:  
- robust study summaries of the studies used as so urces of information;  
- a justification explaining why the sources of information together provide a conclusion 
on the information requirement.  
When nanoforms are covered by the registration , the above approach shall address the 
nanoforms separately.’ ; 
 
(iv) in subsection  1.5. (“Grouping of substances and read -across approach ”), the text  is replaced 
by the following:   
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 ‘Substances whose physicochemical, toxicological and ecotoxicological properties are likely 
to be similar or follow a regular pattern as a result of structural similarity , may be considered 
as a group, or category , of substances. Application of the group concept requires that 
physicochemical properties, human health effects and environmental effects or environmental 
fate may be predicted from data for reference substance(s) within the group by interpolation to 
other  substances in the group (read -across approach). This avoids the need to test every 
substance for every endpoint.  
When nanoforms are covered by the registration , the above approach shall address the 
nanoforms separately. For grouping different nanoforms o f the same substance , the molecular 
structural similarities alone may not serve as a justification.  
If nanoforms covered by a registration are grouped or placed in a “category” with other forms, 
including other nanoforms, of the substance in the same regi stration the obligations above shall 
apply in the same manner.  
The similarities may be based on  any of the following : 
(1) a common functional group;  
(2) the common precursors and/or the likelihood of common breakdown products via 
physical and biological processes,  which result in structurally similar chemicals;  
(3) a constant pattern in the changing of the potency of the properties across the category.  
Structural similarity for UVCB substances shall  be established on the basis of similarities in 
the structures of the c onstituents, together with the concentration of these constituents and 
variability in the concentration of these constituents. If it can be demonstrated that the 
identification of all individual constituents is not technically possible or impractical, the 
structural similarity may be demonstrated by other means, to enable a quantitative and 
qualitative comparison of the actual composition between substances.  
If the group concept is applied, substances shall be classified and labelled on this basis.  
In all c ases, results shall  fulfil all of the following conditions : 
- be adequate for the purpose of classification and labelling and/or risk assessment,  
- have adequate and reliable coverage of the key parameters addressed in the corresponding 
study that shall normal ly be performed for a particular information requirement,  
- cover an exposure duration comparable to or longer than the corresponding study that shall 
normally  be performed for a particular information requirement if exposure duration is a 
relevant parameter . 
In all cases, adequate and reliable documentation of the applied method shall be provided. Such  
documentation shall include:  
- a robust study summary for each source study used in the adaptation;  
- an explanation  why the properties of the registered substanc e may be predicted from 
other substances in the group;  
- supporting information to scientifically justify such explanation  for prediction of 
properties.’ ;   
 
(b) section 3 (“SUBSTANCE -TAILORED EXPOSURE -DRIVEN TESTING ”) is amended as 
follows:   
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 (i) subsection  3.1. is replaced by the following:  
‘3.1. Testing in accordance with Section 8.7 of Annex VIII and in accordance with Annex IX 
and Annex X may be omitted, based on the exposure scenario(s) developed in the Chemical 
Safety Report. Testing in accordance with  Section 8.6.1. of Annex VIII may be omitted only 
for registrants producing less than 100 tonnes per year per manufacturer or importer, based on 
the exposure scenario(s) developed in the Chemical Safety Report.’  
 
(ii) point  3.2(a)(ii) is replaced by the fo llowing : 
 
 
 ‘(ii) a DNEL or a PNEC can be derived from results of available test data for the substance 
concerned taking full account of the increased uncertainty resulting from the omission of the 
information requirement, and that DNEL or PNEC is relevant  and appropriate both to the 
information requirement to be omitted and for risk assessment purposes . For this purpose  and 
without prejudice to column 2 of Section s 8.6 and 8.7 of Annexes IX and X, a DNEL derived 
from a 28 -day repeated dose toxicity study s hall not be considered appropriate to omit a 90 -
day repeated dose toxicity study, and a DNEL derived from a screening test for 
reproductive/developmental toxicity shall not be considered appropriate to omit a prenatal 
developmental toxicity study or an ext ended one -generation reproductive toxicity study.’ .