EN   EN 
 
 
 EUROPEAN  
COMMISSION   
Brussels, XXX   
SANTE/10873/2018 ANNEX CIS 
(POOL/E4/2018/10873/10873 -EN 
ANNEX CIS.docx)  
[…](2019) XXX  draft  
ANNEXES 1 to 2  
 
ANNEXES  
to the  
Commission Delegated Regulation (EU) .../...  
amending Annexes II and III to Regulation (EU) No 528/2012 of the European 
Parliament and of the Council concerning the making available on the market and use 
of biocidal products   EN 1  EN ANNEX I 
Annex II to Regulation (EU) No 528/2012 is amended as follows:    
(1) the introductory part is amended as follows:   
(a) the fifth paragraph of point 2 is replaced by the following:  
‘The applicant shall initiate a pre -submission consultation with the prospective 
evaluating body. In addition to the obligation set out in Article 62(2), applicants may 
also consult with the competent authority that will evalu ate the dossier with regard to 
the proposed information requirements and in particular the testing on vertebrates 
that the applicant proposes to carry out. The applicant shall document such pre -
submission consultation s and their outcomes and shall include the relevant 
documents in the application.'   
(b) point 5 is replaced by the following:  
‘5. Tests submitted for the purpose of the approval of an active substance shall be 
conducted in accord ance with  the methods described in Commission 
Regulation (EC) No 440/ 2008*, or any revised version of these methods not yet 
included in that Regulation . 
However, if a method is inappropriate or not described in Commission 
Regulation (EC) No 440/2008, other methods shall be used which  are 
scientifically appropriate  and their appropriateness shall  be justified in the 
application.  
When test methods are applied to nano -materials, an explanation shall be 
provided of their scientific appropriateness for nanomaterials, and where 
applicable, of the technical adaptations  or adjustments that have been made in 
order to respond to the specific characteristics of these materials.  
_______________  
* Commission Regulation (EC) No 440/2008 of 30 May 2008 laying down test methods 
pursuant to Regulation (EC) No 1907/2006 of the European Parliament and of the Council on the 
Registration, Evaluation, Authorisation and Restriction of Chemicals (REACH ) (OJ L 142, 31.5.2008, 
p. 1).’  
(2) the table in  Title 1 is amended as follows : 
(a) the heading of the  third  column is replaced by the following : 
   ‘Column 3  
Specific rules for adaptation 
from column 1 ’; 
(b) row 2 is replaced by the following:  
‘2 IDENTITY OF THE ACTIVE 
SUBSTANCE (AND ITS 
PRECURSOR( S) IF THE ACTIVE 
SUBSTANCE IS GENERATED IN 
SITU ) 
For the active substance and , if 
applicable,  its precursors, the   EN 2  EN information given in this Section shall 
be sufficient to enable the active 
substance to be identified. If it is not 
technically possible or if it does not 
appear scientifically necessary to give 
information on one or more of the 
items listed in this Section , the 
reasons shall be clearly stated.’  
(c) row 2.5 is replaced by the following:  
‘2.5 Molecular and structural formula 
(including SMILES notation, if 
available and appropriate).  
For precursor(s) and for active 
substances generated in situ, 
information about all generated 
chemical substances (intended and 
unintended).   In case it is not possible to 
exactly define the molecular 
structure of the precursor(s) 
and/or active substance, the 
molecular and structural 
formulas do not need to be 
provided  
 
(d) row 2.8 is replaced by the following:  
‘2.8 Method of manufacture (syntheses 
pathways) of active substance 
including information on starting 
materials and solvents including 
suppliers, specifications and 
commercial availability.  
For active substa nces generated in 
situ, a description of the reaction 
schemes including all intermediate 
reactions and their associated 
chemical substances (intended and 
unintended) shall be provided.’    
(e) the following row 2.11.1 is inserted : 
‘2.11.1  Analytical profile of at least five 
representative samples taken from 
the in situ  generated substance (s), 
providing information on the 
content of the active substance(s) 
and any other constituent  above 
0,1% w/w , including residues of 
precursor(s).’    
(f) row 6.6 is replaced by the following:  
‘6.6 Efficacy data to support:  
– the innate activity of the   EN 3  EN active substance for the 
intended use(s) and  
– any claims made on treated 
articles regarding the biocidal 
properties conferred to the 
article . 
Efficacy data shall includ e any 
available standard protocols, 
laboratory tests or field trials and 
performance standards where 
appropriate, or data similar to those 
available for suitable reference 
products.’  
(g) row 6.7.2 is replaced by the following:  
‘6.7.2  Observations on undesirable or 
unintended side effects on non -target 
organisms or on objects  and material 
to be protected.’    
(h) rows 8.1, 8.2 and 8.3 are  replaced by the following:  
‘8.1 Skin corrosion  or irritation  
The assessment shall comprise the 
followin g tiers:  
(a) assessment of the available 
human, animal and non -
animal data  
(b) skin corrosion , in vitro 
testing  
(c) skin irritation, in vitro testing  
(d) skin corrosion  or irritation, in 
vivo testing   The study/ies in column 1 
do(es) not need to be 
conducted if:  
– the available 
information indicates 
that the substance 
meets the criteria for 
classification for skin 
corrosion  or 
irritation , 
– the substance is a 
strong acid (pH≤2 ,0) 
or base (pH≥11 ,5), 
– the substance is 
spontaneously 
flammable in air or 
in contact with water 
or moisture at room 
temperature , 
– the substance meets 
the classification 
criteria  for acute 
toxicity (Category 1) 
by the dermal route 
or, EN 4  EN – an acute toxicity 
study by the dermal 
route provides 
conclusive evidence 
on skin corrosion  or 
irritation adequate 
for classification . 
If results from one of the two 
studies listed in point (b) or 
point (c) in column 1  of this 
subsection already allow 
conclusive decision on the 
classification of a substance 
or on the absence of skin 
irritation potential, the second 
study does not  need to be 
conducted.  
An in vivo  study for skin 
corrosion  or irritation shall be 
considered only if the in vitro  
studies listed in points (b) and 
(c) in column 1  of this 
subsection are not applicable, 
or the results of these studies 
are not adequat e for 
classification and risk 
assessment . 
In vivo  studies for skin 
corrosion  or irritation that 
were carried out or initiated 
before  … (OJ please insert  
the date of application  of this 
amending Regulation ) shall 
be considered appropriate to 
address this i nformation 
requirement.  
 
8.2 Serious eye damage  or eye irritation  
The assessment shall comprise the 
following tiers:  
(a) assessment of the available 
human, animal and non -
animal data  
(b) serious eye damage  or eye 
irritation,  in vitro  testing  
(c) serious eye damage  or eye  The study/ies in column 1 
do(es) not need to be 
conducted if:  
– the available 
information indicates 
that the substance 
meets the criteria for 
classification for eye 
irritation or causing 
serious damage to EN 5  EN irritation,  in vivo  testing  eyes, 
– the substa nce is a 
strong acid (pH≤2 ,0) 
or base (pH≥11 ,5), 
– the substance is 
spontaneously 
flammable in air or 
in contact with water 
or moisture at room 
temperature or , 
– the substance meets 
the classification 
criteria for  skin 
corrosion  leading to 
classification of th e 
substance as ‘serious 
eye damage’ 
(category 1) . 
If results from a first in vitro  
study do not allow a 
conclusive decision on the 
classification of the substance 
or on the absence of eye 
irritation potential (an)other(s) 
in vitro  study(ies) for this 
endpo int shall be considered.  
An in vivo  study for serious 
eye damage  or eye irritation 
shall be considered only if the 
in vitro  study(ies) listed in  
point (b) in column 1 of this 
subsection are not applicable, 
or the results obtained from 
these studies are not  adequate 
for classification and risk 
assessment . 
In vivo  studies for serious eye 
damage  or eye irritation that 
were carried out or initiated 
before … (OJ please insert  
the date of application  of this 
amending Regulation ) shall 
be considered appropriate to  
address this information 
requirement.  
 EN 6  EN ‘8.3 Skin sensitisation  
The information shall allow to 
conclude whether the substance is a 
skin sensitizer and whether it can be 
presumed to have the potential to 
produce significant sensitisation in 
humans (Category 1A). The 
information should be sufficient to 
perform a risk assessment where 
required.  
The assessment shall comprise the 
following tiers:  
(a) assessment of the available 
human, animal and non -
animal data  
(b) skin sensitisation, in vitro 
testing . Informat ion from in 
vitro  or in chemico  test 
method(s)  referred to  in 
point  5 of the introductory 
part of this Annex and 
addressing each of the 
following key events of skin 
sensitisation:  
(i)molecular interaction with 
skin proteins;  
(ii)inflammatory response in 
keratinocytes;  
(iii)activation of dendritic 
cells.  
(c) skin sensitisation in vivo 
testing . The Murine Local 
Lymph Node Assay (LLNA) 
is the first -choice method for 
in vivo  testing.   Another skin 
sensitisation test may only  be 
used in exceptional cases . If 
another skin sensitisation test 
is used, justification shall be 
provided .  The study/ies in column 1 
do(es) not need to be 
conducted if:  
– the available 
information indicates 
that the substance 
meets the criteria for 
classification for skin 
sensitisation  or skin 
corrosion , 
– the substance is a 
strong acid (pH≤2 ,0) 
or base (pH≥11 ,5) or  
– the substance is 
spontaneously 
flammable in air or 
in contact with water 
or moisture at room 
temperature.  
In vitro  tests do not need to be 
conducted if:  
– an in vivo  study 
refer red to in point 
(c) of column 1  of 
this subsection is 
available or,  
– the available in vitro  
or in chemico test 
methods are not 
applicable for the 
substance or the 
results obtained from 
those studies are not 
adequate for 
classification and 
risk assessment  
If information from test 
method(s) addressing one or 
two of the key events 
described under point (b) in 
column 1 of this subsection 
allows for classification of the 
substance and risk 
assessment, studies 
addressing the other key 
event(s) do not need to be 
conducted.  EN 7  EN An in vivo study for skin 
sensitisation shall be 
conducted only if in vitro  or 
in chemico  test method s 
described under point (b) in  
column 1 of this subsection 
are not applicable, or the 
results obtained from those 
studies are not adequate for 
classification and risk 
assessment.  
In vivo  skin sensitisation 
studies that were carried out 
or initiated before … (OJ 
please insert the date of 
application  of this amending 
Regulation ) shall be 
considered appropriate to 
address this information 
requirement .’ 
(i) row 8.6 is replaced by the following:  
‘8.6 In vivo  genotoxicity study  
The assessment shall comprise the 
following tiers:  
(a) If there is a positive result in 
any of the in vitro  
genotoxicity studies as listed 
in 8.5 and there are no 
reliable results available from 
an appropriate in vivo  
somatic cell genotoxicity 
study, an  appropriate in vivo  
somatic cell genotoxicity 
study shall be conducted.  
(b) A second in vivo somatic  cell 
genotox icity study may be 
necessary depending on the 
in vitro and in vivo  results, 
type of effects, quality and 
relevance of all available data  
(c) If there is a positive result 
from an in vi vo somatic cell 
study available, the potential 
for germ cell mutagenicity 
should be considered based 
on all available data, ADS The study/ies in column 1 
do(es) not need to be 
conducted if:  
– the results are 
negative for the three 
in vitro  tests listed in 
8.5 and no other 
concern has been 
identified (e.g. 
metabolites of 
concern formed in 
mammals) or,  
– the substance meets 
the criteria to be 
classified as a germ 
cell mutagen 
category 1A or 1B  
– The germ cell 
genotoxicity test 
does not need to be 
conducted if the 
substance meets  the 
criteria to be 
classified as a 
carcinogen, category 
1A or 1B and a germ EN 8  EN including toxicokinetic 
evidence to demonstrate that 
the substance reached the 
tested organ. If no clear 
conclusions about germ cells 
mutagenicity can be made, 
additional investigations 
shall be considered  cell mutagen 
category 2. ’ 
(j) rows 8.10 to 8.10.3 are  replaced by the following:  
‘8.10  Reproductive toxicity  
For evaluation of consumer and 
animal safety of active substances that 
may end up in food or feed, it is 
necessary to conduct toxicity studies 
by the oral route.   The studies do not need to be 
conducted if:  
– the substance meets 
the criteria to be 
classified as a 
genotoxic carcinogen  
(classified both as 
germ cell mutagen 
category 2, 1A or 1B 
and carcinogenic 
category 1A or 1B),  
and appropriate risk 
management 
measures are 
implemente d 
including measures 
related to 
reproductive toxicity,  
– the substance meets 
the criteria to be 
classified as a germ 
cell mutagen category 
1A or 1B and 
appropriate risk 
management 
measures are 
implemented 
including measures 
related to 
reproductive toxicity,  
– the substance is of 
low toxicological 
activity (no evidence 
of toxicity seen in 
any of the tests 
available provided 
that the dataset is 
sufficiently EN 9  EN comprehensive and 
informative), it can 
be proven from 
toxicokinetic data 
that no systemic 
absorption occurs  via 
relevant routes of 
exposure (e.g. plasma  
or 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 the pattern of use 
indicates there is n o 
or negligible 
significant h uman or 
animal exposure , 
– the substance meets 
the criteria to be 
classified as 
reproductive 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 will be 
necessary. A full 
justification must be 
provided and 
documented if 
investigations for 
developmental 
toxicity are not 
conducted or,  
– the substance is 
known to cause 
developmental 
toxicity, meeting the 
criteria for 
classification as EN 10  EN reproductive 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 will be 
necessary. A full 
justification must be 
provided and 
documented if 
investigations for 
sexual function and 
fertility is not 
conducted.  
Notwithstanding the 
provisions of this column of 
this subsection , studies  on 
reproductive toxicity may 
need to be conducted to obtain 
information on endocrine 
disrupting properties  as laid 
down in 8.13.3.1.  
 
8.10.1  Pre-natal development toxicity study 
(OECD TG 414) on two species, 
preferred first species is rabbit (non -
rodent)  and preferred second species 
is rat (rodent); oral route of 
administration is the preferred route.   The study on the second 
species shall not be conducted 
if the study performed on the 
first species or other available 
data indicate that the substance 
causes developmental toxicity 
meeting the criteria for 
classification as toxic for 
reproduction category 1A or 
1B: May damage the unborn 
child (H360D), and the 
available data are adequate to 
support a robust risk 
assessment.  
 
‘8.10.2  Extended One -Generation 
Reproductive Toxicity Study (OECD  A two -generation repr oductive 
toxicity study conducted in EN 11  EN TG 443), with cohorts 1A and 1B and 
extension of cohort 1B to include the 
F2 generation with the aim to 
produce 20 litters per dose group, F2 
pups must be followed to weaning 
and investigated simila rly as F1 pups. 
Rat is the preferred species and oral 
route of administration is the 
preferred route.  
The highest dose level should be 
based on toxicity and selected with 
the aim to induce reproductive and/or 
other systemic toxicity.  accord ance with  OECD TG 
416 (adopted 2001 or later) or 
equivalent information  shall be 
considered appropriate to 
address this information 
requirement, if the study is 
available and was initiated 
before  … (OJ please insert the 
date of application  of this 
amending Regulation ). 
 
8.10.3  Developmental neurotoxicity  
Developmental Neurotoxicity Study 
in accord ance with  OECD TG 426, 
or any relevant study (set) providing 
equivalent information, or by cohorts 
2A and 2B of an Extended One -
Generation Reproductive Toxicity 
study (OECD TG 443) with 
additional investigation for cognitive 
functions.   The study shall not be 
conducted if  the available dat a: 
– indicate that the 
substance causes 
developmental 
toxicity and meets the 
criter ia to be classified 
as toxic for 
reproduction category 
1A or 1B: May 
damage the unborn 
child (H360D), and  
– are adequate to 
support a robust risk 
assessment .’ 
(k) the following row 8.10.4 is inserted : 
‘8.10.4  Further studies  
A decision on the need to perform 
additional  studies including those 
informing on the mechanisms should 
be based on the outcome s of the 
studies  listed in 8.10.1, 8.10.2  and 
8.10.3 and all other relevant 
available data.  ADS ’  
(l) row 8.11.2 is replaced by the  following:  
‘8.11.2  Carcinogenicity testing in a second 
species  
(a) A second carcinogenicity 
study should be conducted  The second carcinogenicity  
study does not need to be 
conducted if the applicant can 
justify on the basis of sci entific EN 12  EN using the mouse as test 
species . 
(b) For evaluation of consumer 
safety of active substances 
that may end up in food or 
feed, it is necessary to 
conduct toxicity studies by 
the oral route.  grounds  that it  is not necessary. 
In such cases, scientifically 
validated alternative 
carcinogenicity models may be 
used instead of a second 
carcinogenicity study. ’ 
 
(m) rows 8.12.1 to 8.12.8 are replaced by the following:  
‘8.12.1  Information on signs of poisoning, 
clinical tests, first aid measures, 
antidotes, medical treatment and 
prognosis following poisoning    
8.12.2  Epidemiological studies    
8.12.3  Medical surveillance data, health 
records and case reports.’    
(n) rows 8.13.2 and 8.13.3 are  replaced by the following:  
‘8.13.2  Neurotoxicity  
The preferred test species is the rat 
unless another test species is 
justified to be more appropriate  
For delayed neurotoxicity tests the 
preferred species will be the adult 
hen 
If anticholinesterase activity is 
detected a test for response to 
reactivating agents should be 
considered  
If the active su bstance is an 
organophosphorus compound or if 
there is an indication , knowledge of 
the mechanism of action or  
knowledge from repeat dose studies  
that the active substance may have 
neurotoxic properties , additional 
information or specific studies  will 
be re quired.  
For evaluation of consumer safety of 
active substances that may end up in 
food or feed, it is necessary to 
conduct toxicity studies by the oral 
route.  ADS   EN 13  EN  
8.13.3  Endocrine disruption  
The assessment of endocrine 
disruption shall comprise the 
following tiers:  
(a) An assessment of the 
available information from 
the following studies and 
any other relevant 
information, including in 
vitro  and in silico  methods:  
(i)8.9.1 A 28 -day oral 
study in rodents 
(OECD TG 407)  
(ii)8.9.2 A 90 -day oral 
study in rodents 
(OECD TG 408)  
(iii)8.9.4 A repeated 
dose oral study in non -
rodents (OECD TG 
409) 
(iv)8.10.1 A prenatal 
developmental toxicity 
study (OECD TG 414)  
(v)8.10.2 An extended 
one-generation 
reproductive toxicity 
study (OECD TG 443) 
or two -generation 
reproductive toxicity 
study (OECD TG 416)  
(vi)8.10.3 A 
developmental 
neurotoxicity study 
(OECD TG 426)  
(vii)8.11.1 A 
combined 
carcinogenicity study 
and long -term repeated 
dose toxicity study 
(OECD TG 451 -3) 
(viii) A systematic 
review of the literature 
including studies on 
mammals and non - Where sufficient weight of 
evidence to conclude on the 
presence or absence of a 
particular endocrine disrupting 
mode of action is available:  
– further testing on 
vertebrate animals for 
that effect shall be 
omitted for that mode 
of action ; 
– further testing not 
involving vertebrate 
animals may be 
omitted for that mode 
of action . 
In all cases, adequate and 
reliable documentation shall be 
provided. ’ EN 14  EN mammalian organisms.  
(b) If there is any information 
suggesting that the active 
substance may have 
endocrine disrupting 
properties, or if there is 
incomplete information on 
key parameters relevant for 
concluding on endocrine 
disruption, then additional 
information or specific 
studies shall be required to  
elucidate any of the 
following : 
(1) the mode or the  
mechanism of action ; 
(2) potentially relevant 
adverse effects in 
humans or animals . 
For evaluation of consu mer safety of 
active substances that may end up in 
food or feed, it is necessary to 
consider the oral route and conduct 
animal studies by the oral route . 
(o) the following row 8.13.3.1 is inserted : 
‘8.13.3.1  Specific additional studies to 
investigate potential endocrine 
disrupting properties may include, 
but are not limited to the following:  
(a) the mammalian toxicity 
studies listed in 8.13.3 (a)  
(b) the in vitro  assays:  
(i) Estrogen receptor 
transactivation assay 
(OECD TG 455),  
(ii)Androgen receptor 
transactivation assay, 
(OECD TG 458),  
(iii)H295R steroidogenesis 
assay (OECD TG 
456) 
(iv)the Aromatase assay 
(human 
recombinant)OPPTS ADS’  EN 15  EN 890.1200  
(c) Uterotrophic bioassay in 
rodents (OECD TG 440) 
and Hershberger bioassay 
in rats (OECD TG 441)  
(d) Pubertal development and 
Thyroid Function in Intact 
Juvenile  or Peripubertal 
Male Rats (OPPTS 
890,1500) . 
The decision to carry out studies in 
mammals shall be taken based on all 
available information, including a 
systematic review of the literature 
(including information on endocrine 
disrupting effects in non -target 
organisms) and the availability of 
suitable in silico  or in vitro  methods.  
(p) rows 8.13.4 and 8.13.5 are  replaced by the following:  
‘8.13.4  Immunotoxicity and developmental 
immunotoxicity  
If there is any evidence from repeat 
dose or reproductive toxicity studies 
that the active substance may have 
immunotoxic properties, then 
additional information or specific 
studies shall be required to  elucidate 
any of the following:  
(1) the mode  or the 
mechanism of action ; 
(2) potentially relevant 
adverse effects in 
humans or animals . 
For evaluation of consumer safety of 
active substances that may end up in 
food or feed, it is necessary to 
consider the oral route and conduct 
animal studies by the oral route.  ADS   
 
8.13.5  Further mechanistic studies  
A decision on the need to perform 
additional studies should be based on  
all relevant data.  ADS ’  EN 16  EN (q) row 8.18 is deleted.  
(r) row 9.1.1 is replaced by the following:  
‘9.1.1  Short -term toxicity testing on fish  
When short -term fish toxicity data is 
required, the threshold approach 
(tiered strategy) should be applied.  
A long-term toxicity testing  on fish in 
accordance with  point 9.1.6.1 shall be 
considered if the substance is poorly 
water soluble , i.e. below 1 mg/L .  The study does not need to be 
conducted if:  
– a valid long -term 
aquatic toxicity study 
on fish is available  
– sufficie nt weight of 
evidence includ ing 
the use of existing 
data such as the Fish 
Embryo Acute 
Toxicity (FET , OECD 
TG 236 ) and/or 
results obtained from 
non-animal methods  
is available for this 
data requirement .’ 
(s) row 9.1.6.1 is replaced by the following:  
‘9.1.6.1  Long term toxicity testing on fish 
The information shall be provided 
from long-term toxicity testing on 
fish in which  early life -stages (eggs, 
larvae or juveniles) are exposed . ADS ’  
(t) row 9.10 is replaced by the following:  
‘9.10  Endocrine disruption   
The assessment of endocrine 
disruption properties shall comprise 
the following tiers:  
(a) An assessment of the 
mammalian data set in 
accord ance with 8.13.3 to 
assess whether the substance 
has endocrine disrupting 
properties based on data in 
relation to mammals  
(b) If it cannot be concluded 
based on the mammalian data 
in accordance with 8.13.3 or 
9.1.6.1 that the substance has 
endocrine disrupting 
properties, then  s tudies set 
out in  9.10.1 or 9.10.2 shall   EN 17  EN be considered  taking account 
of any other available 
relevant in formation, 
including a systematic review 
of the literature.’  
(u) the following rows  9.10.1 , 9.10.2 and 9.10.3 are inserted : 
‘9.10.1  Endocrine disruption in fish  
Specific studies to investigate 
potential endocrine disrupting 
properties may include, but are not 
limited to the following data 
requirements:  
(a) Medaka extended one -
generation test (MEOGRT, 
OECD TG 240) ,  
(b) Fish life cycle toxicity test 
(FLCTT, OPPTS 850.1500) 
covering all the ‘estrogen -, 
androgen - and 
steroidogenic -mediated’ 
(EAS) parameters foreseen 
to be measured in the 
MEOGRT study.   The study does not need to be 
carried out if : 
– there is no indication 
for endocrine activity 
or endocrine related 
effects from a 
sufficient  mammalian 
data set in accordance 
with 8.13.3 or from 
any other relevant 
information (e.g. 
literature) and  
– valid in vivo  data is 
available, with no 
information 
suggesting that the 
active substance may 
elicit endocrine 
activity or effects 
potentially related to 
endocrine activity in 
either the Fish short 
term reproduction 
assay (FSTRA; 
OECD TG 229), or 
the 21 -days fish assay 
(OECD TG 230) or 
Fish sexual 
developmental test 
(FSDT, OECD TG 
234). 
If other data are available 
covering the estrogenic, 
androgenic and steroidogenic, 
(EAS) related modalities  or 
parameters investigated in 
OECD TG 229 or OECD TG 
230 or OECD TG 234, then 
those data can be used instead.  
 EN 18  EN 9.10.2  Endocrine disruption in amphibians  
Specific additional studies to 
investigate potential endocrine 
disrupting properties may include, 
but are not limited to Larval 
amphibian growth and development 
assay (LAGDA; OECD TG 241 ).  The study does not need to be 
carried out if :  
– there is no indication 
for endocrine activity 
or endocrine related 
effects from a 
sufficient mammalian 
data set in accordance 
with 8.13.3 or from 
any other relevant 
information (e.g. 
literature) and  
– valid in vivo  data is 
available, with no 
information 
suggesting that the 
active substance may 
have endocrine 
disrupting properties 
in an Amphibian 
metamorphosis assay 
(AMA; OECD 231).  
 
9.10.3  If there is  information suggesting  
that the active substance may have 
endocrine disrupting properties, or if 
there is incomplete information on 
key parameters relevant for 
concluding on endocrine disruption, 
additional information or specific 
studies, as necessary, shall be 
required to  elucidate any of the 
following : 
(a)the mode  or the 
mechanism of action ; 
(b)potentially relevant 
adverse effects in 
humans or animals.  ADS ’  
(3) the table in Title 2 is amended as follows:  
(a) the heading  of the third  column is replaced by the  following : 
    ‘Column 3  
Specific rules for adaptation 
from column 1 ’, EN 19  EN (b) row 2.4 is replaced by the following:  
‘2.4 Specification of the technical grade 
active ingredient.’    
(c) the following rows  2.4.1, 2.4.2 and 2.4.3 are inserted : 
‘2.4.1  Content of the active micro -organism 
and identity and content of relevant 
metabolites  or toxins.    
 
2.4.2  Identity and content of impurities, 
additives,  contaminating micro -
organisms.    
 
2.4.3  Analytical profile of batches.’    
(d) row 2.5 is replaced by the following:  
‘2.5 Method of production and quality 
control.’    
(e) rows  2.6 to 2.9 are  deleted   
(f) row 3.5 is replaced by the following:  
‘3.5 Information on the production of 
relevant metabolites  and toxins.’    
(g) rows  4.1 and 4.2 are replaced by the following:  
‘4.1 Methods, procedures and criteria used 
to establish the presence and identity 
of the micro -organism.    
4.2 Analytical methods for the analysis of 
the micro -organism as manufactured.’    
(h) the following row 4.3 is  inserted : 
‘4.3 Methods used for monitoring 
purposes to  determine and quantify 
residues (viable or non -viable).’    EN 20  EN ANNEX II 
Annex III  to Regulation (EU) No 528/2012  is amended as follows:  
(1) the introductory part is amended as follows :  
(a) ‘the fourth paragraph of point 2 is replaced by the following:  
For some of the information requirements set out in this Annex, it may be possible to 
satisfy these requirements based on available information of the properties of the 
active substance(s)  contained in the product and the properties of non -active 
substanc e(s) included in the product. For non -active substances, applicants shall use 
the information provided to them in the context of Title IV of Regulation (EC) No 
1907/2006, where relevant, and the information made available by the Agency in 
accordance with p oint (e) of Article 77(2) of that Regulation. However, the 
information may be not sufficient or adequate to determine whether a non -active 
substance contained in a biocidal product has hazardous properties and the evaluating 
body  may conclude that further data are required.’   
(b) The seventh  paragraph of point 2 is replaced by the following:  
‘The applicant shall initiate a pre -submission consultation with the prospective 
evaluating body. In addition to the obligation set out in Article 62(2), applicants may 
also consult with the competent authority that will evaluate the dossier with regard to 
the proposed information requirements and in particular the testing on vertebrates 
that the applicant proposes to carry out. The applicant shall document s uch pre -
submiss ion consultation s and their outcomes and shall include the relevant 
documents in the application. ’  
(c) point 5 is replaced by the following:  
‘5. Tests submitted for the purpose of authorisation shall be conducted in 
accord ance with  the methods described in C ommission Regulation (EC) No 
440/2008 or  any revised version of these methods not yet included in that 
Regulation .  
However, if a method is inappropriate or not described in Commission 
Regulation (EC) No 440/2008 *, other methods shall be used which  are 
scientifically appropriate  and their appropriateness shall  be justified in the 
application.  
When test methods are applied to nano -materials, an explanation shall be 
provided of their scientific appropriateness for nanomaterials, and where 
applicable,  of the technical adaptations  or adjustments that have been made in 
order to respond to the specific char acteristics of these materials.  
_______________  
* Commission Regulation (EC) No 440/2008 of 30 May 2008 laying down test methods 
pursuant to Regulation  (EC) No 1907/2006 of the European Parliament and of the Council on the 
Registration, Evaluation, Authorisation and Restriction of Chemicals (REACH) (OJ L 142, 31.5.2008, 
p. 1).’  
(2) The table in Title 1 is amended as follows:  
(a) the heading of the third column is replaced by the following : 
    ‘Column 3  
Specific rules for adaptation EN 21  EN from column 1 ’, 
(b) row 6.6 is replaced by the following:  
‘6.6 The proposed claims for the product 
and, where claims are made, for treated 
articles regarding the biocidal properties 
conferred to the article.’    
(c) row 6.8.2 is replaced by the following:  
‘6.8.2  Observations on undesirable or 
unintended side -effects on non -target 
organisms or on objects  and material to 
be protected.’    
(d) Rows 8.1, 8.2 and 8.3 are  replaced by the following:  
‘8.1 Skin corrosion  or irritation  
The assessment shall comprise the 
following tiers:  
(a) assessment of the available 
human, animal and non -animal 
data  
(b) skin corrosion , in vitro  testing  
(c) skin irritation, in vitro testing  
(d) skin corrosion  or irritation, in 
vivo testing   Testing o f the product  or 
mixture  does not need to be 
conducted if:  
– there are sufficient 
valid data on each 
component of the 
product  or mixture to 
allow its 
classification in 
accord ance with  
Regulation (EC) No 
1272/2008, and 
synergistic effects 
between any of the 
components are not 
expected , 
– the product or 
mixture is a strong 
acid (pH≤2 ,0) or 
base (pH≥11 ,5), 
– the product  or 
mixture is 
spontaneously 
flammable in air or 
in contact with water 
or moisture at room 
temperature,  
– the product  or 
mixture meets the 
classification criteria 
for acute toxicity EN 22  EN category 1 by the 
dermal route or,  
– an acute toxicity 
study by the dermal 
route provides 
conclusive evidence 
on skin corrosion  or 
irritation adequate 
for classification.  
If results from one of the two 
studie s listed in point s (b) or 
(c) in column 1  of this 
subsection  already  allow 
conclusive decision on the 
classification of product  or 
mixture or on the absence of 
skin corrosion  or irritation 
potential, the second study 
does not need to be 
conducted.  
An in vi vo study for skin 
corrosion  or irritation shall be 
considered only if the in vitro  
studies listed in  points (b) and 
(c) in column 1 of this 
subsection are not  applicable, 
or the results of these studies 
are not adequate for 
classification and risk 
assessment and the 
calculation method or 
bridging principles laid down 
in Regulation (EC) No 
1272/2008 are not applicable.  
In vivo  studies that were 
carried out or in itiated before 
… [OJ please insert  the date 
of application of this 
amending Regulation]  shall 
be considered appropriate to 
address  this information 
requirement. ’ 
 
8.2 Serious eye damage  or eye irritation  
The assessment shall comprise the 
following tiers:   Testing on the product  or 
mixture does not need to be 
conducted if:  EN 23  EN (a) assessment of the available 
human, animal and non -animal 
data  
(b) serious eye damage  or eye 
irritation,  in vitro  testing  
(c) serious eye damage  or eye 
irritation,  in vivo testing  – there are suffi cient 
valid data available 
on each component 
of the product  or 
mixture to allow its 
classification in 
accord ance with  
Regulation (EC) No 
1272/2008, and 
synergistic effects 
between any of the 
components are not 
expected,  
– the product  or 
mixture is a strong 
acid (pH≤2 ,0) or 
base (pH≥11 ,5), 
– the product  or 
mixture is 
spontaneously 
flammable in air or 
in contact with water 
or moisture at room 
temperature or,  
– the product  or 
mixture meets the 
classification criteria 
for skin corrosi on 
leading to its 
classification as 
‘serious eye damage’ 
category 1.  
If results from a first in vitro  
study do not allow a 
conclusive decision on the 
classification of the product  or 
mixture or on the absence of 
eye irritation potential 
(an)other(s) in vitro  study(ies) 
for this endpoint shall be 
considered.  
An in vivo  study for serious 
eye damage  or eye irritation 
shall be considered only if the 
in vitro  study(ies) under point 
(b) in column 1 of this 
subsection are not app licable, 
or the results obtained from  EN 24  EN these studies are not adequate 
for classification and risk 
assessment and the 
calculation method or 
bridging principles laid down 
in Regulation (EC) No 
1272/2008 are not applicable.  
In vivo  studies for skin 
corrosion or irritation that 
were carried out or  initiated 
before … (OJ please insert 
the date of application  of this 
amending Regulation ) shall 
be considered appropriate to 
address this information 
requirement.  
 
8.3 Skin sensitisation  
The information shall allow to conclude 
whether the substance is a skin 
sensitiser and whether it can be 
presumed to have the potential to 
produce significant sensitisation in 
humans (Category 1A). The information 
should be sufficient to perform a risk 
assessment where required.  
The assessment shall comprise the 
following  tiers:  
(a) assessment of the available 
human, animal and non -animal 
data 
(b) skin sensitisation, in vitro. 
Information from in vitro  or in 
chemico  test method(s) 
conducted in accordance with 
point 5 of the introductory part 
of this Annex  and addressing 
each of the following key 
events of skin sensitisation:  
(i)molecular interaction 
with skin proteins;  
(ii)inflammatory 
response in 
keratinocytes;  
(iii)activation  of  Testing on the product  or 
mixture does not need to be 
conducted if:  
– there are sufficient 
valid data available 
on each component 
of the product  or 
mixture to allow its 
classification in 
accord ance with  
Regulation (EC) No 
1272/2008 , and 
synergistic effects  
between any of the 
components are not 
expected , 
– the available 
information indicates 
that the product  or 
mixture should be 
classified for skin 
sensitisation or skin 
corrosi on, 
– the product  or 
mixture is a strong 
acid (pH≤2 ,0) or 
base (pH≥11 ,5) or,  
– the produ ct or 
mixture is EN 25  EN dendritic cells.  
(c) skin sensitisation in vivo. The 
Murine Local Lymph Node 
Assay (LLNA) is the first -
choice method for in vivo  
testing. Another skin 
sensitisation test may only be 
used in exceptional 
circumstances . If another skin 
sensitisation test is used, 
scientific justification shall be 
provided.  spontaneously 
flammable in air or 
in contact with water 
or moisture at room 
temperature.  
In vitro  tests do not need to be 
conducted if:  
– an in vivo  study 
referred to in point 
(c) in column 1 of 
this subsection is 
available or,  
– the available  in vitro  
or in chemico test 
methods are not 
applicable for the 
product  or mixture or 
the results obtained 
from these studies 
are not adequate for 
classification and 
risk assessment.  
If information from test 
method(s) addressing one or 
two of the key events 
described in point (b) in 
column 1 of thi s subsection 
already allows for 
classification of the substance 
and risk assessment, studies 
addressing the other key 
event(s) do not  need to be 
conducted.  
An in vivo study for skin 
sensitisation shall be 
considered only if in vitro  or 
in chemico  studies referred to 
in point (b) in column 1 of 
this subsection are not 
applicable, or the results 
obtained from these studies 
are not adequate for 
classification and risk 
assessment and the 
calculation method or 
bridging principles laid down 
in Regulation (EC) No 
1272/2008 are not applicable.  EN 26  EN In vivo  studies that were 
carried out or initiated before 
… (OJ please insert the date 
of application  of this 
amending Regulation ) shall 
be considered appropriate to 
address this information 
requirement.’  
(e) row 8.7 is replaced by the following:  
‘8.7 Available toxicological data relating to : 
(a) non-active substance(s) (i.e. 
substance(s) of concern)  and, 
(b) a mixture  that a substance(s) of 
concern is a component of  
Tests listed in Section 8 of the table in 
Title 1 of Annex II shall be carried out  
for the substance(s) of concern or a 
mixture that a substance(s) of concern 
is a component of if insufficient data 
are avai lable and cannot be inferred 
through read -across, in silico  or other 
accepted non -testing approaches.   Testing on the product  or 
mixture does not need to be 
conducted if  all of the 
following conditions are met : 
– there are valid data 
available on each of 
the components in 
the mixture to allow 
classification of the 
mixture in 
accord ance with  the 
rules laid down in 
Regulation (EC) No 
1272/2008,  
– a conclusion can be 
made whether the 
biocidal product can 
be considered as 
having endocrine 
disrupting properties , 
– synergistic effects 
between any of the 
components are not 
expected. ’ 
(f) row 9.1 is replaced by the following:  
‘9.1 Available ecotoxicological data relating 
to: 
(a) non-active substance(s) (i.e. 
substance(s) of concern),  
(b) a mixture that a substance(s) of 
concern i s a component of  
Tests listed in Section 9 of Title 1 of 
Annex II  shall be carried out for the 
substance(s) of concern or a mixture 
that a substance(s) of concern is a  Testing on the product  or 
mixture does not need to be 
conducted if  all the following 
conditions are met : 
– there are valid data 
available on each of 
the components in 
the mixture to allow 
classification of the 
mixture in 
accord ance with  the EN 27  EN component of if insufficient data are 
available and cannot be inferred 
through read -across, in silico  or other 
accepted non -testing approaches .  rules laid down in 
Regulation (EC) No 
1272/2008,  
– a conclusion can be 
made whether the 
biocidal product can 
be considered a s 
having endocrine 
disrupting properties ,  
– synergistic effects 
between any of the 
components are not 
expected .’ 
(3) the table in  Title 2 is amended as follows:  
(a) the heading of the third  column is replaced by the follow ing: 
    ‘Column 3  
Specific rules for adaptation 
from column 1 ’, 
(b) row 2.3 is replaced by the following:  
‘2.3 Detailed quantitative (g/kg, g/l, % w/w 
(v/v), cfu/g, cfu/l or IU/mg or any other 
appropriate unit) and qualitative 
information on the constitution, 
composition and function of the 
biocidal product, e.g. micro -organism, 
active substance(s) and non -active 
substances and any other relevant 
components.  
All relevant information on individual 
ingredients and the final composition of 
the biocidal product shall be given.’    
(c) rows  3.6.8  to 3.6.12 are deleted  
(d) the following rows 3.6.8 and 3.6.9 are  inserted : 
‘3.6.8  Spraying patterns - aerosols    
 
3.6.9  Other technical characteristics ’   
(e) rows 4 to 4.12.3 are replaced by the following  
4. PHYSICAL HAZARDS AND   EN 28  EN RESPECTIVE CHARACTERISITICS  
‘4.1. Explosives    
4.2. Flammable aerosols    
4.3. Flammable liquids     
4.4. Flammable solids    
4.5. Oxidising liquids    
4.6. Oxidising solids    
4.7. Corrosive to metals    
4.8. Other physical indications of  hazard    
4.8.1.  Auto -ignition temperatures of products 
(liquids and gases)    
4.8.2.  Relative self -ignition temperature  for 
solids    
4.8.3.  Dust explosion hazard’    
(f) row 10.3 is replaced by the following:  
‘10.3  Leaching behaviour and mobility  in soil  ADS’