COMMISSION REGUL ATION (EU) 2018/605 
of 19 Apr il 2018 
amending Annex II to Regulation (EC) No 1107/2009 by setting out scientif ic criter ia for the 
deter mination of endocr ine disr upting proper ties 
(Text with EEA relevance) 
THE EUR OPEAN COMMISSION, 
Having regar d to the Treaty on the Functioning of the European Union, 
Having regar d to Regulation (EC) No 1107/2009 of the European Parliament and of the Council of 21 October 2009 
concer ning the placing of plant prote ction products on the mark et and repealing Council Directives 79/117/EEC and 
91/414/EEC (1), and in particular Article 78(1)(a) and the second paragraph of point 3.6.5 of Annex II thereto, 
Whereas: 
(1)  Scientific criteria for the deter mination of endocr ine disrupti ng proper ties of active substances, safen ers and 
synergists, should be developed taking into account the objectives of Regulation (EC) No 1107/2009, which are 
to ensure a high level of prote ction of both human and animal health and the environment, in particular 
ensur ing that substances or products placed on the mark et have no harmful effect on human or animal health or 
unaccep table effects on the environment, and to improve the functioning of the internal market while improving 
agricultural production. 
(2)  In 2002, the World Health Organisation (WHO) through its Intern ational Programme for Chemical Safet y 
proposed a definition for endocr ine disruptors (2) and in 2009 a definition of adverse effects (3). Those definitions 
have by now reached the widest consensus among scientists. The European Food Safety Auth ority (‘the 
Author ity’) endorsed those definitions in its Scientifi c Opinion on endocr ine disruptors adop ted on 28 Febr uary 
2013 (4) (hereinaf ter ‘the Scientific Opinion of the Auth ority’). Such is also the view of the Scientific Committ ee 
on Consumer Safety (5). It is theref ore appropr iate to base the criteria for the determination of endocr ine 
disrupti ng proper ties on those WHO definit ions. 
(3)  In order to implement those criteria, weight of evidence should be applied consider ing in particular the approac h 
provid ed for in Regulation (EC) No 1272/2008 of the European Parliament and of the Council (6) on the weight 
of evidence. Previous exper ience with the Guidance document on standardised test guidelines for evaluating 
chemicals for endocr ine disruption of OECD (7) should also be considered. In addition, the implementation of the 
criteria should be based on all relevant scientific evidence, including studies submitte d in accordance with the 
current regulatory data requirements of Regulation (EC) No 1107/2009. These studies are mostly based on inter­
nationally agreed study prot ocols. 
(4)  The deter mination of endocr ine disrupting proper ties with respect to human health should be based on human 
and/or animal evidence, theref ore allowing for the identif ication of both known and presumed endocr ine 
disrupti ng substances. 20.4.2018 L 101/33 Official Jour nal of the European Union EN     
(1)OJ L 309, 24.11.2009, p. 1. 
(2)WHO/IPCS (World Health Organization/Int ernational Programme on Chemical Safet y), 2002. Global Assessment of the State-of-the- 
science of Endocr ine Disr uptors. WHO/PCS/EDC/02.2, publicly avail able at http://www .who.int/ipcs/publications/new_ 
issues/endocr ine_disr uptors/en/ 
(3)WHO/IPCS (World Health Organization/Int ernational Programme on Chemical Safety), 2009. Principles and Methods for the 
Risk Assessment of Chemicals in Food. Environment al Health Criteria 240, publicly available at http://www .who. 
int/f oodsaf ety/publications/chemical-f ood/en/ 
(4)‘Scientific Opinion on the hazard assessment of endocr ine disruptors: Scientif ic criteria for identification of endocr ine disruptors and 
appropr iateness of existing test methods for assessing effec ts mediated by these substances on human health and the environment ’, EFSA 
Journal 2013;11(3):3132, doi: 10.2903/j.efsa.2013.3132. 
(5)Scientific Committee on Consumer Safet y, Memorandum on Endocr ine disruptors, 16.12.2014 (SCCS/1544/14). 
(6)Regulation (EC) No 1272/2008 of the European Parliament and of the Council of 16 December 2008 on classification, labelling and 
packaging of substances and mixtures, amending and repealing Directives 67/548/EEC and 1999/45/EC, and amending Regulation (EC) 
No 1907/2006 (OJ L 353, 31.12.2008, p. 1). 
(7)OECD Series on Testing and Assessment No 150. (5)  As the specific scientific criteria laid down by this Regulation reflect the current scientifi c and technical 
kno wledge and are to be applied instead of the criteria currently set out in point 3.6.5 of Annex II to Regulation 
(EC) No 1107/2009, they should be provid ed for in that Annex. 
(6)  In order to take into account the current scientific and technical knowledg e, specifi c scientifi c criteria should also 
be specifi ed in order to identify active substances, safen ers or synergists having endocr ine disrupting proper ties 
that may cause adverse effects on non-target organisms. Theref ore point 3.8.2 of Annex II to Regulation (EC) 
No 1107/2009 should be amended to introduce these specifi c criteria. 
(7)  The Commission should assess, in light of the objectives of Regulation (EC) No 1107/2009, the exper ience 
gained from the application of the scientific criteria for the determination of endocr ine disrupting proper ties 
introduced by the present Regulation. 
(8)  The criteria for the deter mination of endocr ine disrupti ng proper ties reflect the current state of scientifi c and 
technical kno wledge and allow identifying active substances having endocr ine disrupti ng proper ties more 
accurat ely. The new criteria should theref ore apply as soon as possible, while taking into account the time 
necessar y for Member States and the Author ity to prepare for applying those criteria. Theref ore, from 20 October 
2018, those criteria should apply excep t where the relevant Committee has voted on a draf t Regulation by 
20 October 2018. The Commission will consider the implications for each procedure pending under Regulation 
(EC) No 1107/2009 and, where necessar y, take appropr iate measures with due respect for the rights of the 
applicants. This may include a request for additional information from the applicant and/or for additional 
scientific input from the rappor teur Member State and the Author ity. 
(9)  The measures provi ded for in this Regulation are in accordance with the opinion of the Standing Committee on 
Plants, Animals, Food and Feed, 
HAS ADOPTED THIS REGUL ATION: 
Article 1 
Annex II to Regulation (EC) No 1107/2009 is amended in accordance with the Annex to this Regulation. 
Article 2 
Points 3.6.5 and 3.8.2 of Annex II to Regulation (EC) No 1107/2009, as amended by this Regulation, shall apply as of 
20 October 2018, excep t for procedures where the Committee has voted on a draf t Regulation by 20 October 2018. 
Article 3 
By 20 October 2025, the Commission shall present to the Committ ee referred to in Article 79 of Regulation (EC) 
No 1107/2009 an assessment of the exper ience gained from the application of the scientific criteria for the determina ­
tion of endocr ine disrupti ng proper ties introduced by this Regulation. 
Article 4 
This Regulation shall enter into force on the twentieth day followi ng that of its publication in the Official Journal of the 
European Union. 
It shall apply from 20 October 2018. 
This Regulation shall be binding in its entirety and directly applicable in all Member State s. 
Done at Brussels, 19 Apr il 2018. 
For the Commission 
The President 
Jean-Claude JUNCK ER  20.4.2018 L 101/34 Official Jour nal of the European Union EN     ANNEX 
Annex II to Regulation (EC) No 1107/2009 is amended as follows:  
(1) in point 3.6.5 the follo wing paragraphs are added after the fourth paragraph: 
‘From 20 Octobe r 2018, an active substance, safener or synergist shall be considered as having endocr ine disrupti ng 
proper ties that may cause adverse effect in humans if, based on points (1) to (4) of the sixth paragraph, it is 
a substance that meets all of the follo wing criteria, unless there is evidence demonstrating that the adverse effects 
identif ied are not relevant to humans:  
(1) it shows an adverse effect in an intact organism or its progen y, whic h is a change in the mor phology , 
physiology , growth, development, reproduction or life span of an organism, system or (sub)population that 
results in an impairm ent of functional capacity , an impair ment of the capacity to compen sate for additional 
stress or an increase in susceptibility to other influences;  
(2) it has an endocr ine mode of action, i.e. it alters the function(s) of the endocr ine syste m;  
(3) the adverse effect is a consequence of the endocr ine mode of action. 
The identif ication of an active substance, safen er or synergist as having endocr ine disrupti ng proper ties that may 
cause adverse effect in humans in accordance with the fifth paragraph shall be based on all of the follo wing points:  
(1) all available relevant scientific data (in vivo studies or adequately validat ed alternative test systems predictive of 
adverse effects in humans or animals; as well as in vivo, in vitro, or, if applicable, in silico studies informing 
about endocr ine modes of action): 
(a)  scientifi c data generated in accordance with intern ationally agreed study prot ocols, in particular those liste d 
in the Commission Communications in the framew ork of setting out the data requirements for active 
substances and plant protect ion products, in accordance with this Regulation; 
(b)  other scientifi c data selected applying a system atic review methodology , in particular followi ng guidance on 
literature data whic h is liste d in the Commission Communications in the framework of setting out the data 
requirements for active substances and plant prot ection products, in accordance with this Regulation;  
(2) an assessment of the available relevant scientific data based on a weight of evidence approach in order to 
establish whether the criteria set out in the fifth paragraph are fulfilled; in applying the weight of evidence deter­
mination, the assessment of the scientific evidence shall, in particular , consider all of the follo wing factors: 
(a)  both positive and negat ive results; 
(b)  the relevance of the study designs, for the assessment of adverse effects and of the endocr ine mode of 
action; 
(c)  the quality and consist ency of the data, consider ing the patter n and coherence of the results within and 
between studies of a similar design and across diffe rent species; 
(d)  the route of exposure, toxicokinetic and metabolism studies; 
(e)  the concept of the limit dose, and international guidelines on maximum recommended doses and for 
assessing conf ounding effects of excessive toxicity ;  
(3) using a weight of evidence approach, the link between the adverse effect(s) and the endocr ine mode of action 
shall be established based on biological plausibility , whic h shall be determi ned in the light of current scientific 
knowle dge and under consideration of internationally agreed guidelines;  
(4) adverse effects that are non-specif ic secondar y consequences of other toxic effects shall not be considered for the 
identif ication of the substance as endocr ine disruptor.’; 20.4.2018 L 101/35 Official Jour nal of the European Union EN     (2) in point 3.8.2 the follo wing paragraphs are added after the sole paragraph: 
‘From 20 Octobe r 2018, an active substance, safener or synergist shall be considered as having endocr ine disrupti ng 
proper ties that may cause adverse effects on non-target organisms if, based on points (1) to (4) of the third 
paragraph, it is a substance that meets all of the follo wing criteria, unless there is evidence demonstrating that the 
adverse effects identified are not relevant at the (sub)population level for non-target organisms:  
(1) it shows an adverse effect in non-target orga nisms, which is a change in the mor phology , physiology , growth, 
development, reproduction or life span of an organism, system or (sub)population that results in an impair ment 
of functional capacity , an impair ment of the capacity to compen sate for additional stress or an increase in sus­
cepti bility to other influences;  
(2) it has an endocr ine mode of action, i.e. it alters the function(s) of the endocr ine syste m;  
(3) the adverse effect is a consequence of the endocr ine mode of action. 
The identif ication of an active substance, safen er or synergist as having endocr ine disrupti ng proper ties that may 
cause adverse effects on non-target organisms in accordance with the second paragraph shall be based on all of the 
followi ng points:  
(1) all available relevant scientific data (in vivo studies or adequately validat ed alternative test systems predictive of 
adverse effects in humans or animals; as well as in vivo, in vitro, or, if applicable, in silico studies informing 
about endocr ine modes of action): 
(a)  scientifi c data generat ed in accordance with internati onally agreed study prot ocols, in particular , those listed 
in the Commission Communications in the framew ork of setting out the data requirements for active 
substances and plant protect ion products, in accordance with this Regulation; 
(b)  other scientifi c data selected applying a system atic review methodology , in particular followi ng guidance on 
literature data listed in the Commission Communications in the framew ork of setting out the data 
requirements for active substances and plant prot ection products, in accordance with this Regulation;  
(2) an assessment of the available relevant scientific data based on a weight of evidence approach in order to 
establish whether the criteria set out in the second paragraph are fulfilled; in applying the weight of evidence de­
term ination, the assessment of the scientific evidence shall consider all of the follo wing factors: 
(a)  both positive and nega tive results, discr iminating between taxonomic groups (e.g. mammals, birds, fish, 
amphibians) where relevant ; 
(b)  the relevance of the study design for the assessment of the adverse effects and its relevance at the (sub) 
population level, and for the assessment of the endocr ine mode of action; 
(c)  the adverse effects on reproduction, growth/development, and other relevant adverse effects which are likely 
to impact on (sub)populations. Adequate, reliable and representative field or monitoring data and/or results 
from population models shall as well be considered where available; 
(d)  the quality and consist ency of the data, consider ing the patter n and coherence of the results within and 
between studies of a similar design and across diffe rent taxonomic groups; 
(e)  the concep t of the limit dose and international guidelines on maximum recommended doses and for 
assessing conf ounding effects of excessive toxicity .  
(3) using a weight of evidence approach, the link between the adverse effect(s) and the endocr ine mode of action 
shall be established based on biological plausibility , whic h shall be determi ned in the light of current scientific 
knowle dge and under consideration of internationally agreed guidelines;  
(4) Adverse effects that are non-specifi c secondar y consequences of other toxic effects shall not be considered for 
the identif ication of the substance as endocr ine disruptor with respect to non-targe t organisms.’  20.4.2018 L 101/36 Official Jour nal of the European Union EN