COMMISSION STAFF WORKING DOCUMENT FITNESS CHECK on endocrine disruptors Accompanying the document COMMUNICATION FROM THE COMMISSION TO THE EUROPEAN PARLIAMENT, THE COUNCIL, THE EUROPEAN ECONOMIC AND SOCIAL COMMITTEE AND THE COMMITTEE OF THE REGIONS Chemicals Strategy for Sustainability Towards a Toxic-Free Environment
Date: 2020-10-14
Institutions: Directorate-General for Environment, European Commission
Subjects: EU strategy, chemical product, chemicals legislation, endocrine disease, endocrine disruptor, environmental protection, public health, toxic substance

EN 

  EN 

   EUROPEAN COMMISSION  Brussels, 14.10.2020  SWD(2020) 251 final  COMMISSION STAFF WORKING DOCUMENT  FITNESS CHECK on endocrine disruptors Accompanying the document COMMUNICATION FROM THE COMMISSION TO THE EUROPEAN PARLIAMENT, THE COUNCIL, THE EUROPEAN ECONOMIC AND SOCIAL COMMITTEE AND THE COMMITTEE OF THE REGIONS Chemicals Strategy for Sustainability     Towards a Toxic-Free Environment {COM(2020) 667 final} - {SWD(2020) 225 final} - {SWD(2020) 247 final} - {SWD(2020) 248 final} - {SWD(2020) 249 final} - {SWD(2020) 250 final}  
 
 
TABLE OF CONTENTS  

1 INTRODUCTION ................................................................................................................... 9 

1.1  Background to the Fitness Check ................................................................................. 9 

1.2  Objectives of the Fitness Check ................................................................................. 13 

2  METHODOLOGY ............................................................................................................ 14 

2.1 

2.2 

Scope of the Fitness Check ........................................................................................ 14 

Fitness Check questions and baseline ........................................................................ 15 

2.3  Mapping of of regulatory provisions and review of key documents .......................... 16 

2.4  Case studies ................................................................................................................ 16 

2.5  Consultation activities ................................................................................................ 16 

3 

STATE OF PLAY ............................................................................................................. 17 

4  COHERENCE ................................................................................................................... 31 

4.1  Data requirements ...................................................................................................... 33 

4.2  Hazard identification .................................................................................................. 38 

4.3  Risk assessment .......................................................................................................... 43 

4.4  Risk management ....................................................................................................... 49 

4.5  Coherence with non-EU jurisdictions ........................................................................ 55 

5  EFFECTIVENESS ............................................................................................................ 57 

5.1  Current process of ED identification .......................................................................... 58 

5.2  Biocidal Products and Plant Protection Products Regulations ................................... 64 

5.3  REACH ...................................................................................................................... 68 

5.4  Other sector-specific and product-specific legislation ............................................... 72 

5.5  Communication .......................................................................................................... 78 

5.6  Monitoring data .......................................................................................................... 79 

5.7  Human health and environmental impact evidence and indicators ............................ 81 

5.8  Market surveillance .................................................................................................... 83 

5.9 

Functioning of the internal market, competitiveness and innovation ........................ 84 

6  EFFICIENCY .................................................................................................................... 85 

7  RELEVANCE ................................................................................................................... 90 

7.1  Relevance to citizens and stakeholders ...................................................................... 90 

7.2  Ability to adapt to the evolving societal and economic context ................................ 93 

7.3  Ability to adapt to scientific progress ........................................................................ 94 

8  EU ADDED VALUE ........................................................................................................ 97 

8.1 

Joining forces and efficient use of resources ............................................................. 97 

1 

 
 
 
8.2 

Preserving the functioning of the single market ......................................................... 98 

8.3  Legislative measures alignment between Europe and global regimen ...................... 99 

9  CONCLUSIONS ............................................................................................................. 103 

10  REFERENCES ................................................................................................................ 109 

11  GLOSSARY .................................................................................................................... 114 

Annex 1.  Procedural information ........................................................................................... 117 

1  Lead DG and internal references ..................................................................................... 117 

2  Organisation and timing .................................................................................................. 117 

3  Exceptions to the better regulation guidelines ................................................................. 118 

4  Consultation of the Regulatory Scrutiny Board .............................................................. 118 

5  Evidence, sources and quality ......................................................................................... 120 

Annex 2.  Synopsis report: stakeholder consultation activities .............................................. 121 

1 

2 

3 

Summary .......................................................................................................................... 121 

Introduction and approach ............................................................................................... 122 

Stakeholder groups covered by the consultation activities .............................................. 122 

4  Outcome of the public consultation ................................................................................. 124 

4.1  Respondents ............................................................................................................. 124 

4.2  How well informed do citizens feel? ........................................................................ 124 

4.3 

4.4 

4.5 

4.6 

4.7 

Public views on effectiveness .................................................................................. 126 

Public views on efficiency ....................................................................................... 126 

Summary of public views on regulatory testing and animal welfare ....................... 127 

Public views on EU-added value ............................................................................. 127 

Public views on relevance ........................................................................................ 127 

4.8  Additional comments made by citizens ................................................................... 127 

5  Outcome of the stakeholder consultation ........................................................................ 129 

5.1 

Structure of survey ................................................................................................... 129 

5.2  Respondents ............................................................................................................. 129 

5.3 

5.4 

5.5 

5.6 

5.7 

5.8 

Familiarity of stakeholders with relevant legislation ............................................... 132 

Stakeholder views on coherence (overall statistics) ................................................. 132 

Stakeholder views on effectiveness (overall statistics) ............................................ 135 

Stakeholder views on efficiency (overall statistics) ................................................. 142 

Stakeholder views on relevance (overall statistics) .................................................. 144 

Stakeholder views on EU-added value (overall statistics) ....................................... 145 

5.9  Breakdown of stakeholder views according to stakeholder group ........................... 146 

6  Outcome of the SME consultation................................................................................... 150 

2 

 
 
6.1  Respondents ............................................................................................................. 150 

6.2  Legislation affecting respondents ............................................................................. 150 

6.3 

6.4 

6.5 

6.6 

6.7 

Information in the company about endocrine disruptors ......................................... 150 

SME views on coherence ......................................................................................... 151 

SME views on effectiveness .................................................................................... 151 

SME views on efficiency ......................................................................................... 152 

SME views on EU added value ................................................................................ 153 

6.8  Additional comments made by SMEs ...................................................................... 153 

Annex 3.  Methodology .......................................................................................................... 155 

1 

Summary .......................................................................................................................... 155 

2  Workflow ......................................................................................................................... 155 

3 

Preliminary analysis of current situation ......................................................................... 156 

3.1  Questionnaire to policy DGs .................................................................................... 156 

3.2 

Identification of Regulatory Reviews/Better Regulation activities .......................... 156 

3.3  Definition of scope ................................................................................................... 156 

3.4 

Formulation of Fitness Check questions .................................................................. 158 

4  Extraction and review of available evidence ................................................................... 158 

4.1  Mapping of provisions ............................................................................................. 158 

4.2 

Policy and scientific sources of evidence ................................................................. 158 

4.3  Evidence base and limitations .................................................................................. 159 

4.4  Case studies .............................................................................................................. 159 

4.5  Evidence base and limitations .................................................................................. 159 

4.6  Economic case studies .............................................................................................. 159 

5  Consultation activities ..................................................................................................... 161 

5.1  External consultation activities ................................................................................ 161 

5.2  Evidence base and limitations .................................................................................. 161 

Annex  4.    Mapping  of  provisions  and  regulatory  processes  for  identifying  and  managing 
Endocrine Disruptors .............................................................................................................. 162 

1  Biocidal Products ............................................................................................................. 163 

2 

Plant Protection Products and residues ............................................................................ 165 

3  REACH ............................................................................................................................ 166 

4  Classification, Labelling and Packaging (CLP) .............................................................. 168 

5 

POPs Regulation .............................................................................................................. 169 

6  Toys ................................................................................................................................. 170 

7 

Food legislation ............................................................................................................... 170 

3 

 
 
7.1 

Food Contact Materials ............................................................................................ 170 

7.2  Contaminants in feed and food................................................................................. 172 

7.3 

Food additives .......................................................................................................... 172 

8  Cosmetic Products ........................................................................................................... 173 

9  Medical devices and in vitro diagnostics ......................................................................... 175 

10  Human and veterinary medicines .................................................................................... 175 

11  Occupational Safety and Health legislation (OSH) ......................................................... 177 

12  Water ............................................................................................................................... 178 

13  Chemical-product-waste interface ................................................................................... 179 

14  Other in-scope legislation ................................................................................................ 181 

14.1  Detergents ................................................................................................................. 181 

14.2  Fertilising Products .................................................................................................. 181 

14.3  Ecolabel Regulation ................................................................................................. 182 

14.4  General Product Safety Directive ............................................................................. 182 

14.5  Seveso III Directive and Industrial Emission Directive ........................................... 183 

14.6  Directive on air quality ............................................................................................. 184 

14.7  WTO rules ................................................................................................................ 184 

15  References ....................................................................................................................... 186 

Annex 5A. Case Study: 3-benzylidene camphor (3-BC) ........................................................ 187 

1  Case study factsheet: overview of concerns for human health and environment and main 
regulatory intervention ............................................................................................................ 187 

2 

Substance profile ............................................................................................................. 188 

2.1  Exposure pathways of concern ................................................................................. 188 

2.2  Effects on human health and the environment ......................................................... 188 

3 

3-BC and structurally similar UV filters in EU legislation ............................................. 189 

3.1  Regulating 3-BC in cosmetics legislation ................................................................ 189 

3.2  Regulating 3-BC under REACH .............................................................................. 191 

3.3 

Status of structurally similar UV filters ................................................................... 192 

4  Comments on fitness check evaluation criteria ............................................................... 194 

5  References ....................................................................................................................... 196 

Annex 5B. Case Study: bis(2-ethylhexyl) phthalate (DEHP) ................................................. 198 

1  Case study factsheet: overview of concerns for human health and environment and main 
regulatory intervention ............................................................................................................ 198 

2 

Substance profile ............................................................................................................. 201 

2.1  Exposure pathways of concern ................................................................................. 201 

2.2  Hazard endpoints of concern .................................................................................... 202 

4 

 
 
3  DEHP and other phthalates in EU legislation ................................................................. 204 

3.1  Regulating phthalates under REACH and preceding legislation ............................. 204 

3.2  Enforcement of regulatory measures under REACH ............................................... 206 

3.3  Regulating phthalates under food contact materials (FCM) .................................... 207 

3.4  Regulating DEHP in cosmetics ................................................................................ 209 

3.5  Regulating DEHP in medical devices ...................................................................... 209 

3.6  Regulating DEHP at the interface of chemical and waste legislation ...................... 210 

3.7  Regulating DEHP under the Water Framework Directive ....................................... 211 

4 

Impact of regulation ......................................................................................................... 212 

4.1  Decline in use and exposure ..................................................................................... 212 

4.2 

Shift to alternatives ................................................................................................... 212 

5  Comments on fitness check evaluation criteria ............................................................... 214 

6  References ....................................................................................................................... 216 

Annex 5C. Case Study: nonylphenol ...................................................................................... 219 

1  Case study factsheet: overview of concerns for human health and environment and main 
regulatory intervention ............................................................................................................ 219 

2 

Substance profile ............................................................................................................. 220 

2.1  Exposure pathways of concern ................................................................................. 221 

2.2  Effects on human health and the environment ......................................................... 222 

3  Regulating nonylphenols in EU legislation ..................................................................... 222 

3.1  Regulating nonylphenols in REACH ....................................................................... 223 

3.2  Regulating nonylphenols under other chemical legislation ..................................... 227 

3.3  Regulating nonylphenols under the Water Framework Directive ............................ 227 

4 

Impact of regulation ......................................................................................................... 228 

4.1  Reduced exposure .................................................................................................... 228 

4.2 

Shift to alternatives ................................................................................................... 229 

5  Comments on fitness check evaluation criteria ............................................................... 230 

6  References ....................................................................................................................... 232 

5 

 
 
 
 
ABBREVIATIONS 

Abbreviation 

Explanation 

3-BC 

AOP 

AR 

BAT 

BBP 

BCF 

3-Benzylidene camphor 

Adverse Outcome Pathway 

Androgen Receptor 

Best Available Techniques 

Benzyl Butyl Phthalate 

Bioconcentration Factor 

BREF 

BAT reference documents 

BPA 

BPR 

CA 

CF 

CLP 

CMR 

CPR 

DBP 

DEHP 

DIBP 

DNT 

DWD 

EAS 

EATS 

EC 

ECHA 

ED 

EFSA 

ELoC 

Bisphenol A 

Biocidal Products Regulation 

Competent Authority 

Conceptual  Framework  (OECD  Conceptual  Framework  for  Testing  and 
Assessment of Endocrine Disrupters) 

Classification, Labelling and Packaging 

Carcinogenic, Mutagenic or toxic for Reproduction 

Cosmetic Products Regulation 

Dibutyl phthalate 

Diethylhexyl phthalate 

Diisobutyl phthalate 

Developmental neurotoxicity  

Drinking Water Directive 

Endocrine Active Substance 

Estrogen, Androgen, Thyroid, Steroidogenic 

European Commission 

European Chemicals Agency 

Endocrine Disruptor 

European Food Safety Authority 

Equivalent Level of Concern 

EOGRTS 

Extended-One-Generation Reproductive Toxicity Study 

EQS 

ER 

ESAC 

EURL 
ECVAM 

Environmental Quality Standard 

Estrogen Receptor 

ECVAM Scientific Advisory Committee 

European Union Reference Laboratory for alternatives to animal testing 

6 

 
 
 
Abbreviation 

Explanation 

FAO 

FC 

FCM 

GD 

GPSD 

IATA 

ICH 

IPCS 

IVDR 

JRC 

LMWP 

LOAEL 

LOEC 

MDR 

MoA 

MRL 

MSC 

MS 

NAM 

NGO 

NGRA 

NOEC 

NP 

OECD 

OML 

OSH 

PBT 

PCB 

PEC 

PHS 

PFAS 

PNEC 

POP 

PPP 

Food and Agriculture Organization 

Fitness Check 

Food Contact Material 

Guidance document 

General Product Safety Directive 

Integrated Approach(es) to Testing and Assessment 

International  Council  for  Harmonisation  of  Technical  Requirements  for 
Pharmaceuticals for Human Use 

International Programme on Chemical Safety 

In Vitro Diagnostics Regulation 

Joint Research Centre 

Low Molecular Weight Phthalates 

Lowest observed adverse effect level 

Lowest observed effect concentration 

Medical Devices Regulation  

Mode of Action 

Maximum Residue Level 

Member State Committee 

Member State 

New Approach Methodology 

Non Governmental Organisation 

Next Generation Risk Assessment 

No Observed Effect Concentration 

Nonylphenol 

Organisation for Economic Cooperation and Development 

Overall Migration Limit 

Occupational Safety and Health legislation 

Persistent, Bioaccumulative and Toxic 

Polychlorinated biphenyl 

Predicted Environmental Concentration  

Priority Hazardous Substance 

Per- and polyfluoroalkyl substances 

Predicted No Effect Concentration 

Persistent Organic Pollutant 

Plant Protection Product 

7 

 
 
Abbreviation 

Explanation 

PPPR 

PS 

RAC 

Plant Protection Products Regulation 

Priority Substance 

(ECHA) Risk Assessment Committee 

REACH 

Registration, Evaluation, Authorisation and Restriction of Chemicals 

RoHS 

SEAC 

SCCP 

SCCS 

Restriction of Hazardous Substances 

(ECHA) Socio-Economic Analysis Committee 

Scientific Committee on Consumer Products (replaced by the SCCS) 

Scientific Committee on Consumer Safety 

SCHEER 

Scientific Committee on Health, Environmental and Emerging Risks 

SCoPAFF 

Standing Committee on Plants, Animals, Food and Feed 

SME 

SML 

SPS 

Small and Medium-sized Enterprise 

Specific Migration Limit 

(Agreement on the Application of) Sanitary and Phytosanitary Measures  

SVHC 

Substance of Very High Concern 

TG 

TBT 

TDI 

UNEP 

UN GHS 

UWWD 

VICH 

vPvB 

WFD 

WHO 

WoE 

WTO 

Test Guideline 

(Agreement on) Technical Barriers to Trade  

Tolerable Daily Intake 

United Nations Environment Programme 

United Nations Globally Harmonised System 

Urban Waste Water Directive  

International  Cooperation  on  Harmonisation  of  Technical  Requirements  for 
Registration of Veterinary Medicinal Products 

very Persistent and very Bioaccumulative 

Water Framework Directive 

World Health Organization 

Weight of Evidence 

World Trade Organization  

8 

 
 
 
 
 
1 INTRODUCTION 

  Endocrine Disruptors are chemicals that can negatively affect the health of humans or animals by 

altering the functioning of the hormonal system. 

  The EU has taken a progressive series of actions on endocrine disruptors since 1999. 
  Different regulatory approaches exist in different pieces of legislation. 
  To  address  concerns  about  possible  inconsistencies  between  different  pieces  of  legislation,  the 

Commission launched a Fitness Check in 2019. 

  The Fitness Check focused mainly on the evaluation criteria of coherence and effectiveness, but 

also addressed efficiency, relevance and EU added value. 

  Background to the Fitness Check 

1.1
Endocrine  Disruptors  (EDs)  are  chemical  substances  that  can  alter  the  functioning  of  the  endocrine 
(hormonal) system and negatively affect the health of humans or animals. The EU response to EDs 
has developed over the past twenty years, in line with the actions outlined in the Community Strategy 
for  Endocrine  Disruptors1.  Significant  progress  in  understanding  these  substances  has  been  made 
since then. 

Overviews  of  the  state  of  the  science  on  EDs  have  been  published  by  various  bodies.  Notably,  in 
2012,  the  United  Nations  Environment  Programme  (UNEP)  and  the  World  Health  Organization 
(WHO) published an update (WHO/UNEP, 2012) of the 2002 International Programme on Chemical 
Safety (IPCS) report (IPCS, 2002). This report notes the increase in trends of many endocrine-related 
disorders  in  humans,  and  associations  between  exposure  to  EDs  and  some  diseases.  It  also 
acknowledges the multi-causal nature of the diseases and the resulting difficulty in attributing a given 
disease  to  a  single  factor,  such  as  chemical  exposure.  The  report  also  emphasises  the  existence  of 
critical  windows  of  exposure  (such  as  foetal  development  and  puberty)  during  which  exposure  can 
lead to irreversible effects, some being detected only many years later. Furthermore, the report gives 
examples  of  wildlife  populations  recovering  after  decreased  exposure  to  EDs.  Finally,  the  need  to 
develop appropriate testing methods is highlighted.  

Endocrine  disruption  is  a  relatively  new  consideration  in  toxicological  or  eco-toxicological 
assessment,  whereby  the  focus  is  on  the  way  in  which  a  chemical  disrupts  the  development  and 
functioning of humans or organisms (i.e. through disturbing hormonal balance) eventually leading to 
an adverse effect (or effects) on function that arises as a consequence of the disturbance, where the 
nature  of  the  adverse  effects  may  vary  according  to  the  timing  of  the  exposure  and  the  species 
exposed.  

For  some  chemicals,  adverse  effects,  such  as  cancers  in  hormone-sensitive  organs,  or  reproductive 
and developmental disorders, may already be known, and the chemicals already flagged as substances 
of  concern  (e.g.  through  classification  as  hazardous  under  the  EU  Classification  Labelling  and 
Packaging (CLP) Regulation2), have been banned or restricted on the basis of these adverse effects.  

1COM(1999) 706. 
2Classification, Labelling and Packaging of substances and mixtures (EC) No 1272/2008 

9 

 
 
 
 
                                                      
The  significance  of  non-monotonic  dose–response  relationships  and  low-dose  effects  of  endocrine 
disruptors  has  been  widely  debated  and  there  is  still  no  consensus  in  the  scientific  community  on 
whether  and  how  certain  toxicological  principles  such  as  the  ‘safe  threshold’,  (i.e.  the  dose  below 
which no adverse effect is expected to occur) are applicable in assessing the safety of EDs. This lack 
of  agreement  presents  particular  difficulties  at  the  policy  level  in  deciding  how  risk  assessments 
should be conducted for these chemicals and whether to follow a generic risk approach or a specific 
risk approach3 (Solecki et al., 2017). 

A  variety  of  EU  regulatory  measures  address  the  risks  from  exposure  to  hazardous  chemicals. 
Collectively,  these  measures  aim  to  ensure  a  high  level  of  protection  of  human  health  and  the 
environment, while ensuring the smooth functioning of the internal market. Some pieces of legislation 
have  specific  provisions  for  EDs  (i.e.  chemicals  in  general  (REACH),  plant  protection  products, 
biocidal  products,  water  and  medical  devices).  For  other  pieces  of  legislation,  with  no  ED-specific 
provisions, there are general provisions for the risk management of hazardous substances which may 
be used to control the risks posed by EDs (once they are identified). 

EU action on EDs relies largely on work undertaken by the EU scientific assessment bodies, such as 
the independent scientific committees (on Consumer Safety – SCCS – and on Health, Environmental 
and Emerging Risks – SCHEER), the European Chemicals Agency (ECHA) and the European Food 
Safety  Authority  (EFSA).  Following  the  hazard  or  risk  assessments  conducted  by  these  bodies,  the 
Commission takes the final decision on risk management measures, together with the Member States 
and  the  other  European  Institutions  (Council  and  Parliament)  as  appropriate.  When  scientific 
evaluation  cannot  conclude  with  sufficient  certainty  on  a  risk,  the  Commission  is  guided  by  the 
precautionary principle to take protective measures for its citizens and/or the environment. 

For plant protection products and biocidal products, the co-legislators decided – as for other hazard 
properties of particular concern (such as substances classified as carcinogenic, mutagenic, or toxic to 
reproduction, categories 1A or 1B) that once it is proven that a substance is an endocrine disruptor, 
the  substance  in  principle  cannot  be  authorised  for  use;  while  there  are  very  limited  derogation 
possibilities. For biocides, the ban is only applicable in relation to ED properties for human health and 
not for the environment. 

Criteria  for  identifying  endocrine  disruptors  have  been  established  under  the  legislation  on  plant 
protection  products4  and biocidal  products5.  These  criteria  were  informed  by  various  EU  initiatives. 
These included the work  of a Endocrine Disrupters Expert  Advisory Group  (Munn and Goumenou, 
2013a, b) and of the EFSA Scientific Committee  (EFSA Scientific Committee, 2013), as well as an 
impact assessment of different options for the criteria6. The criteria are based on the 2002 IPCS/WHO 
definition  (IPCS,  2002),  according  to  which  an  endocrine  disruptor  is  “an  exogenous  substance  or 

3In generic risk approaches (referred also as hazard-based approaches) risk management measures are taken 
directly based on the identified hazard classification (generic risk consideration). In specific risk approaches 
(referred also as risk-based approaches) risk management measured are taken based on the outcome of a risk 
assessment, considering both exposure and hazard.  
4Commission Regulation (EU) 2018/605 of 19 April 2018 amending Annex II to Regulation (EC) No 1107/2009 
by setting out scientific criteria for the determination of endocrine disrupting properties (plant protection 
products) 
5Commission Delegated Regulation (EU) 2017/2100 of 4 September 2017 setting out scientific criteria for the 
determination of endocrine-disrupting properties pursuant to Regulation (EU) No 528/2012 of the European 
Parliament and Council 
6SWD(2016) 211 

10 

 
 
                                                      
mixture that alters function(s) of the endocrine system and consequently causes adverse health effects 
in  an  intact  organism,  or  its  progeny,  or  (sub)populations”.  In  practical  terms,  this  means  that  the 
identification  of  a  substance  as  an  ED  should  be  based  on  an  adverse  effect  for  which:  a)  there  is 
convincing evidence of a biologically plausible causal link to an endocrine disrupting mode of action; 
and  b)  disruption  of  the  endocrine  system  is  not  a  secondary  consequence  of  other  non-endocrine-
mediated systemic toxicity. 

EU  legislation  in  fields  other  than  plant  protection  products  and  biocidal  products  does  not  contain 
such criteria. It has been argued by stakeholders that the same criteria should apply across the relevant 
pieces of EU chemicals legislation for reasons of legal certainty and in order to avoid the possibility 
that a substance is identified as an ED under one piece of legislation and not under another. 
Different  regulatory  approaches  exist  in  different  pieces  of  legislation  for  substances  that  have 
endocrine disrupting properties. According to some pieces of legislation, these substances cannot in 
principle  be  authorised  for  use,  unless  limited  derogation  possibilities  apply.  Under  other  pieces  of 
legislation, chemicals with endocrine disrupting properties may be authorised for a limited period or a 
limited range of uses, or under restricted conditions.  

Other pieces of legislation do not mention EDs specifically, however, substances with such properties 
can be subject to case-by-case regulatory action based on the general requirements of the legislation.  

Efforts  to  identify,  assess  and  manage  risk  from  EDs  under  REACH  have  been  underway  for  some 
time  and  two  EDs  (ethoxylates  of  octylphenol  and  nonylphenol)  have  been  placed  on  the  list  of 
substances (Annex XIV) requiring specific authorisations to be on the market. A further 15 substances 
have been identified as substances of very high concern (SVHCs) with endocrine disrupting properties 
and are included in the Candidate list of substances for possible inclusion in the authorisation list in 
the  future;  another  80  or  more  are  currently  being  evaluated  due  to  concern  about  their  potential 
endocrine disrupting properties. Substances with ED properties can also be subject to restrictions, e.g. 
four phthalates at a  sum level of 0.1% or higher in a variety of products7. Time has been relatively 
short  since  the  criteria  to  assess  active  substances  used  in  biocidal  products  and  plant  protection 
products  came  into  force  (2018).  Nevertheless,  three  biocidal  active  substances  and  three  active 
substances  in  plant  protection  products  (PPP)  have  already  been  identified  as  EDs  for  both  human 
health  and  the  environment  and  a  further  four  PPP  active  substances  identified  as  EDs  for  human 
health8.  Table  1.1  provides  a  list  of  the  substances  identified  as  SVHCs  with  endocrine  disrupting 
properties  under  REACH  or  identified  as  EDs  under  the  Biocidal  Products  Regulation  as  of 
September 2020.  

7See Annex XVII of REACH.   
8Relevant EFSA conclusions are adopted but not yet published and hence not included in Table 1.1. 

11 

 
 
 
 
 
 
                                                      
 
Table 1.1 Substances identified as endocrine disruptors at EU level9 

Name and abbreviation 

CAS no.10 

Effects 

Legislation 

2,2-dibromo-2-cyanoacetamide  

10222-01-2 

Cyanamide 

Cholecalciferol 

3-benzylidene camphor  

420-04-2 

67-97-0 

15087-24-8 

Human Health and 
Environment 
Human health and 
Environment 
Human Health and 
Environment 
Environment 

4-(1,1,3,3-tetramethylbutyl)phenol  

140-66-9 

Environment 

4-(1,1,3,3-tetramethylbutyl)phenol, ethoxylated 

N/A 

Environment 

4-heptylphenol, branched and linear  

4-Nonylphenol, branched and linear 

N/A 

N/A 

Environment 

Environment 

4-Nonylphenol, branched and linear, ethoxylated  N/A 

Environment 

4-tert-butylphenol  

98-54-4 

Environment 

Benzyl butyl phthalate (BBP)  

85-68-7 

Human Health 

Bis(2-ethylhexyl) phthalate (DEHP)  

117-81-7 

Bisphenol A  

Butyl 4-hydroxybenzoate 

Dibutyl phthalate (DBP)  

Dicyclohexyl phthalate (DCHP)  

Diisobutyl phthalate  

p-(1,1-dimethylpropyl)phenol  

80-05-7 

94-26-8 

84-74-2 

84-61-7 

84-69-5 

80-46-6 

Human Health and 
Environment 
Human Health and 
Environment 
Human Health 

Human Health 

Human Health 

Human Health 

Environment 

N/A 

Environment 

Reaction products of 1,3,4-thiadiazolidine-2,5-
dithione, formaldehyde and 4-heptylphenol, 
branched and linear (RP-HP) with ≥0.1% w/w 4-
heptylphenol, branched and linear  
Tris(4-nonylphenyl, branched and linear) 
phosphite (TNPP) with ≥ 0.1% w/w of 4-
nonylphenol, branched and linear (4-NP)  

BPR 

BPR 

BPR 

REACH 

REACH 

REACH 

REACH 

REACH 

REACH 

REACH 

REACH 

REACH 

REACH 

REACH 

REACH 

REACH 

REACH 

REACH 

REACH 

N/A 

Environment 

REACH 

Under the legislation on water, the Commission has included several endocrine disruptors in the list of 
“priority  substances”  of  particular  concern  in  surface  waters,  for  which  environmental  quality 
standards  and  emission  controls  apply.  Furthermore,  the  Commission  has  included  several 
demonstrated  or  suspected  endocrine  disruptors  in  the  "watch  list"  of  substances  for  which  Union-
wide monitoring data should be gathered.  

9See also Table 5.1 for further details 
10N/A: not applicable 

12 

 
 
 
 
 
                                                      
Due to possible concerns of endocrine disruption, the chemical bisphenol A was banned from use in 
baby  bottles  and  other  containers  for  foods  for  infants  and  young  children  on  the  basis  of  the 
precautionary  principle,  and  very  low  migration  limits  are  set  for  other  food  contact  materials. 
Bisphenol A is also subject to limit values in toys for young children under 36 months or intended to 
be placed in the mouth and paper used in receipts. An occupational exposure limit value for bisphenol 
A has also been set to protect workers from exposure through inhalable dust.  

On  7  November  2018,  the  Commission  adopted  its Communication  “Towards  a  comprehensive  EU 
framework on endocrine disruptors”11, updating the Strategy of 1999. The Communication confirms 
the  Commission's  commitment  to  protect  EU  citizens  and  the  environment  from  EDs.  It  outlines 
actions to step up the EU approach in order to further progress and maintain the expected high level of 
protection.  In  particular,  to  address  the  concerns  on  the  coherence  of  the  EU  legal  framework,  the 
Communication announced the launch of this cross-cutting Fitness Check on EDs. While evaluations 
or Fitness Checks of relevance for EDs had already been carried out or are under way, a systematic 
analysis of the coherence of relevant provisions on EDs across the EU regulatory measures had not 
yet been completed. This was therefore a particular focus of this Fitness Check. 

1.2

  Objectives of the Fitness Check 

EU regulatory measures that address the risks from exposure to endocrine disruptors (EDs) have been 
developed at different points in time and have, in certain cases, different specific objectives. This has 
resulted  in  different  approaches  for  managing  endocrine  disruptors,  depending  on  the  sector  being 
regulated. Collectively, these measures aim to ensure a high level of protection of human health and 
the  environment,  while  ensuring  the  smooth  functioning  of  the  internal  market.  While  regulatory 
measures have allowed protective action to be taken against these substances (e.g. by introducing bans 
or restrictions on their use), questions have been raised by stakeholders on the overall coherence of 
the EU legal framework in relation to EDs. 

To  address  the  concerns  on  the  coherence  of  the  EU  legal  framework,  the  Commission  launched  a 
cross-cutting Fitness Check on EDs12, with the objectives to assess: 

1)  the coherence of the relevant EU legislation, including an analysis of how different provisions in 

different legal instruments interact, identifying potential gaps or inconsistencies. 

2)  whether EU chemicals legislation is effective in delivering its objective to protect human health 

and the environment by minimising the overall exposure to endocrine disruptors. 

3)  to  the  extent  possible,  the  efficiency,  relevance  and  EU  added-value  of  the  relevant  EU 

chemicals legislation. 

In addressing these objectives, particular attention is paid to legislation that does not contain specific 
provisions  for  endocrine  disruptors,  such  as  the  legislation  on  toys,  cosmetics  and  food  contact 
materials. Another focal point is on whether the different pieces of legislation take into account the 
protection of vulnerable population groups that are particularly sensitive to endocrine disruptors when 
assessing  and  regulating  such  substances.  The  international  dimension  is  also  assessed,  taking  into 
account the impact of EU provisions on trade flows within and outside the EU. The findings of this 
Fitness Check will feed into the forthcoming Chemicals Strategy on Sustainability. 

11COM(2018) 734 
12Fitness Check initiative and roadmap: https://ec.europa.eu/info/law/better-regulation/have-your-
say/initiatives/2142-Fitness-Check-on-endocrine-disruptors 

13 

 
 
 
 
 
 
                                                      
2  METHODOLOGY 

  The methodology identifies the legislation considered to be in the scope of the Fitness Check 
  A series of questions were formulated to guide the interpretation of the five evaluation criteria 

(coherence, effectiveness, efficiency, relevance and EU-added value). 

  Four main evidence streams were generated to inform the findings: a) mapping of regulatory 
provisions related to the identification or risk management of endocrine disruptors; b) review 
of  key  policy  and  scientific  documents;  c)  chemical  specific  case  studies  to  illustrate  the 
interplay  between  different  pieces  of  legislation;  and  d)  the  results  of  consultations  with  the 
public, stakeholders and SMEs.  

2.1

  Scope of the Fitness Check 

The  horizontal  nature  of  the  Fitness  Check  requires  a  broad  scope,  covering  many  legal  acts 
addressing  chemicals  that  are  relevant  to  human  health  and  the  environment.  For  much  of  the 
chemicals acquis, Fitness Checks and other 'Better Regulation' activities addressing specific pieces of 
legislation had been completed or were ongoing.  

On  the  basis  of  the  mandate  of  the  Fitness  Check  described  in  the  Commission  Communication 
“Towards a comprehensive EU framework on endocrine disruptors”, in-scope legislation was defined 
as  legislation  including  provisions  for  the  identification,  hazard  assessment,  risk  assessment  or  risk 
management of chemicals with endocrine disrupting properties for human health and the environment. 
The legislation considered in scope is listed in Table 2.1. 

Table 2.1 Legislation in scope for this Fitness Check 

Legislation 

Plant Protection Products Regulation (EC) No 1107/2009 

Maximum Residue Levels of Pesticides Regulation (EC) No 396/2005 

Biocidal Products Regulation (EU) No 528/2012 

REACH Regulation (EC) No 1907/2006 

CLP: Classification, Labelling and Packaging of substances and mixtures (EC) No 1272/2008 

Persistent Organic Pollutants Regulation (EU) 2019/1021 

Food contact materials Regulation (EC) No 1935/2004  

Contaminants in food Regulation (EEC) No 315/93 and in feed Directive 2002/32/EC 

Food Additives Regulation (EC) No 1333/2008  

Cosmetic Products Regulation (EC) No 1223/2009 

Medical Devices Regulation (EU) 2017/745  

In Vitro Diagnostic Medical Devices Regulation (EU) 2017/746  

Toy Safety Directive 2009/48/EC 

14 

 
 
 
 
 
 
Legislation 

Fertilising Products Regulation (EU) 2019/1009 

Detergents Regulation (EC) No 648/2004 

Medicinal Products for Human Directive 2001/83/EC * 

Coverage here limited to unintended exposure via the environment (see also Annex 4) 

Veterinary Medicinal Products Regulation (EU) 2019/6 * 

Coverage here limited to unintended exposure via the environment (see also Annex 4) 

General Product Safety Directive 2001/95/EC 

Water Framework Directive 2000/60/EC  

Priority substances Directive 2013/39/EU 

Drinking Water Directive 98/83/EC  

Groundwater Directive 2006/118/EC 

Marine Strategy Framework Directive 2008/56/EC 

Urban Waste Water Directive 91/271/EEC 

Chemical Agents at Work Directive 98/24/EC 

Carcinogens and Mutagens at Work Directive 2004/37/EC 

Pregnant Workers Directive 92/85/EEC 

Young People at Work Directive 94/33/EC 

Waste Directive 2008/98/EC  

Restriction of the use of certain hazardous substances in electrical and electronic equipment Directive 
2011/65/EU 

Industrial emissions (integrated pollution prevention and control) Directive 2010/75/EU 

Seveso-III-Directive 2012/18/EU 

Ambient Air Quality and Cleaner Air for Europe Directive 2008/50/EC 

EU Ecolabel Regulation (EC) No 66/2010  
*EU Pharmaceuticals Strategy is under development 

2.2

  Fitness Check questions and baseline 

The evaluation questions placed emphasis on coherence issues across the different in-scope regulatory 
instruments  in  Table  2.1.  To  apply  the  Fitness  Check  questions,  it  was  necessary  to  establish  a 
baseline  for  comparison.  When  a  temporal  reference  needs  to  be  established,  the  baseline  is  the 
situation with no specific provisions in EU legislation, corresponding to the year of adoption of the 
first  strategy  on  endocrine  disruptors  (1999).  The  evaluation  questions  relate  to  the  specific  policy 
interventions  or  non-interventions  across  the  different  regulatory  sectors  from  1999  to  date  (e.g. 
implementation  of  REACH  or  the  establishment  of  ED  criteria  for  plant  protection  products  and 
biocidal  products).  Other  points  of  reference,  such  as  non-EU  jurisdictions,  were  considered  when 
appropriate. 

15 

 
 
 
2.3

  Mapping of of regulatory provisions and review of key documents 

Annex 3 describes the approach taken to map regulatory provisions related to the identification or risk 
management of endocrine disruptors, and to review key policy and scientific documents.  

2.4

  Case studies 

Case  studies  were  developed  for  specific  chemicals  that  are  regulated  under  different  and 
interconnected  legislative  instruments,  with  the  aim  to  provide  representative  examples  illustrating 
how EDs are identified, assessed and managed across legislation for their effects on human health and 
the environment. Substances selected for the case studies: 

  3-Benzylidene camphor (3-BC; under assessment under REACH and the Cosmetic Products 

Regulation; endocrine disruptor with human health and environmental concern) 

  Diethylhexyl  phthalate  (DEHP;  regulated  under  several  pieces  of  legislation:  REACH, 
cosmetic products, medical devices, food contact materials, toys, Water Framework Directive 
(WFD); endocrine disruptor with human health and environmental concern) 

  Nonylphenol  (NP;  regulated  under  REACH  (covering  many  sectors:  detergents,  biocides, 
plant  protection  products,  cosmetic  products,  medical  devices),  WFD;  endocrine  disruptor 
with environmental concern) 

Two  economic  case  studies  were  also  carried  out  to  explore  possible  associations  between  the 
implementation of risk management measures on selected chemicals and trade flows, both within and 
between the EU and non-EU countries  (Canzian et al., 2020).  

The main criterion for selecting case studies was that the substances should be relevant to more than 
one policy area, thereby enabling an analysis of the coherence of the assessment and risk management 
approaches  applied.  DEHP,  3-BC  and  nonylphenols  and  their  ethoxylates  are  regulated  by  various 
pieces  of  in-scope  legislation,  including  the  ones  specifically  mentioned  in  the  Fitness  Check 
mandate.  DEHP  and  nonylphenols  are  representative  of  two  main  groups  of  substances  which  have 
been  identified  as  SVHCs  with  endocrine  disrupting  properties  (phthalates,  alkylphenols)  and  for 
which  risk  management  measures  have  been  applied.  Thus,  the  case  studies  were  chosen  to  be  as 
representative  and  informative  as  possible,  from  the  pool  of  SVHCs  with  endocrine  disrupting 
properties that were identified at the time of selection. (see Table 1.1). 

2.5

  Consultation activities 

2.5.1  External consultation activities 

Consultation activities were carried out to gather inputs from a broad range of stakeholder  groups as 
well as citizens to ensure that views from all interested parties were considered in the evaluation. The 
consultation  activities  relied  primarily  on  the  results  of  three  surveys  aimed  at  the  general  public, 
stakeholders and SMEs. The results were used as an additional source of evidence, recognising that 
they are associated with an inevitable bias towards those who have an interest in responding. Further 
information on the approach and findings is given in Annex 2. 

16 

 
 
 
 
 
 
3  STATE OF PLAY 

Substances  with  endocrine  disrupting  properties  can  be  present  in  a  wide  range  of  materials  and 
products.  Some  are  incorporated  in  formulations  intended  for  direct  applications  to  humans  (e.g. 
cosmetic products) or in the environment (e.g. plant protection products). Some are directly released 
upon  product  application  (cosmetic  products,  plant  protection  products).  Others  are  incorporated  in 
materials  and  may  be  released  over  longer  time  scales  along  the  product  life  cycle,  from 
manufacturing  to  waste  and  possibly  from  recycled  material  streams.  The  system  of  EU  regulation 
dealing  with  chemicals  aims  at  minimising  exposure  of  humans  and  the  environment  to  EDs  from 
different  sources  and  exposure  pathways.  Figure  3.1  illustrates  at  which  stage  of  a  product’s  life 
cycle, from manufacturing to waste, specific legislation is intended to act. Overall, risk management 
provisions  (intervention  logic)  aim  to  strike  a  balance  between  human  health  and  environmental 
protection, the societal benefits of the use of chemicals and the smooth functioning of the EU single 
market.  

Figure 3.1. EU legislation (not exhaustive) mapped against pathways of endocrine disruptors’ exposure to 
humans and the environment13 

Annex 4 provides a detailed analysis of regulatory provisions and processes in place relevant to the 
control of endocrine disruptors for each piece of EU legislation in the scope of this Fitness Check. It 
also  provides  an  overview  of  international  legal  obligations  (WTO).  Many  pieces  of  legislation 
regulate  the  placing  on  the  market  of  chemicals,  and  materials  and  products  containing  them 

13See Annex 4 for a detailed description of legal provisions and processes for identification, assessment and 
management of EDs. 

17 

 
 
 
 
                                                      
(horizontal list in the centre of Figure 3.1). Their scope is complementary with respect to human and 
environmental  protection,  with  the  REACH  regulation  setting  the  baseline  for  general  chemicals 
(Figure 3.1). These regulations and directives form the core of EU chemical legislation, together with 
the Classification, Labelling and Packaging (CLP) Regulation. Table 3.1 summarises the intervention 
logic  of  each  piece  of  ‘in scope’  legislation  and  highlights  the different  approaches  implemented  to 
manage  EDs  or  which  could  be  used  to  manage  EDs  (for  those  regulations  that  do  not  contain  ED 
specific  provisions).  The  Table  also  shows  the  main  interlinkages  between  various  pieces  of 
4). 
legislation 

Annex 

details 

(more 

given 

are 

in 

18 

 
 
Table 3.1 Overview of intervention logic and provisions for endocrine disruptors within in-scope legislation 

Legislation 

Intervention logic 

ED identification 
provisions 

Hazard assessment of 
endocrine disrupting 
properties 

Provisions for management 
of substances with endocrine 
disrupting properties 

Main links with 
other legislation 

Plant 
Protection 
Products 
Regulation 
(EC) 
1107/2009 

Protection  of  human  and  animal 
health  and 
the  environment  from 
exposure  to  hazardous  chemicals  in 
plant protection products by: 
 

regulating  the  authorisation  for 
placing  on  the  market  and  use  of 
plant protection products  
regulating  the  approval  of  active 
substances, safeners and synergists  

No 

 

Maximum 
Residue 
Levels 
Pesticides 
Regulation 
(EC) 
396/2005 

of 

No 

Biocidal 
Products 
Regulation 
(EU) 
528/2012 

No 

of 

consumers 

Protection 
from 
unacceptable risk to pesticide residues 
in  food  and  feed  of  plant  and  animal 
origin by: 

  determining  maximum  levels  of 

pesticide residues   

Protection  of  human  and  animal 
health  and 
the  environment  from 
exposure  to  hazardous  chemicals  in 
biocidal products by: 

Yes.  

 

regulating  the  approval  of  active 
substances  which  may  be  used  in 

Yes 

Criteria for ED identification 
introduced in 201814. 

ED-specific  and  generic  risk 
approach with limited options 
for 
(negligible 
exposure and essential use). 

derogation 

No 

Specific risk approach 

for 

ED 
Criteria 
identification  are 
in 
essence  the  same  as 
Biocidal 
for 
Products Regulation. 

the 

in 
Co-formulants 
protection 
plant 
products  have  to  be 
registered 
under 
REACH. 

Hazard  identification 
is  covered  under  the 
Protection 
Plant 
Products Regulation. 

Criteria for ED identification 
introduced in 201814. 

ED-specific  and  generic  risk 
approach with limited options 
for  derogation  (negligible  risk, 
essential  use,  disproportionate 
negative  impacts  on  society 
compared to the risk from use). 

for 

ED 
Criteria 
identification  are 
in 
essence  the  same  as 
Plant 
the 
for 
Protection 
Products 
Regulation. 

14Data requirements for plant protection products, biocidal products and REACH substances are currently under revision to increase their capacity for providing data on 
endocrine disrupting properties  

19 

 
 
 
 
 
 
                                                      
Legislation 

Intervention logic 

ED identification 
provisions 

Hazard assessment of 
endocrine disrupting 
properties 

Provisions for management 
of substances with endocrine 
disrupting properties 

Main links with 
other legislation 

biocidal products 
regulating  the  authorisation  for 
placing  on  the  market  and  use  of 
biocidal products  

Protects the public (citizens, workers, 
consumers) and the environment from 
exposure 
to  hazardous  chemicals, 
while  promoting  alternative  methods 
of 
for 
substances by: 

assessment 

hazards 

of 

REACH 
Regulation 
(EC) 
1907/2006 

No 

 

the  placing  on 

regulating 
the 
market  of  chemicals  (on  its  own, 
from  articles) 
in  mixtures  or 
through 
registrations, 
authorisation and restrictions  
  communication  of  hazards,  risks 
and safe use conditions throughout 
supply chain 

Very 

Yes, 
identification 
of ED as Substances 
High 
of 
(SVHCs) 
Concern 
possible through Art 
57 (f).  

industry 

obligations 
Registration 
to  assess 
require 
hazards  of  substances.  Data 
requirements 
on 
tonnage14. 

depend 

endocrine 
Assessment  of 
disrupting  properties  through 
substance evaluation, SHVC-
identification  and  as  part  of 
restrictions.   

in 
Co-formulants 
biocidal 
products 
have  to  be  registered 
under REACH. 

Several 
provisions 
under  REACH  (e.g. 
registration, 
on 
authorisation, 
restriction)  apply  also 
to chemicals regulated 
or 
sector- 
under 
product-related 
legislation, 
explicitly 
under REACH. 

unless 
excluded 

SVHCs 

EDs  are  listed  as  SVHCs  if 
meeting  the  “Equivalent  Level 
of  Concern”  criteria.  SVHC 
listing 
risk 
(generic 
approach) triggers notification 
provisions. 
are 
regulated through authorisation 
and 
through 
specific  risk  approaches  and 
risk-benefit approaches.  
Restrictions  can  be  based  on 
endocrine disrupting properties 
if they lead to an unacceptable 
risk. 

restrictions 

that 

emissions 

Registrants have to ensure that 
risks  from  manufacturing  or 
use of chemicals are controlled 
or 
are 
minimised.  Hazard  properties 
including  endocrine  disrupting 
properties  have  to  be  reported 
via safety data sheets to ensure 
safe use  throughout the  supply 
chain. 

CLP: 
Classification, 
Labelling  and 

Protects  human  health  and 
environment by: 

the 

No 

disrupting 
Endocrine 
properties are covered if they 
lead  to  a  substance  fulfilling 

Hazard-based.  Classification 
of  substances  as  Carcinogenic, 
Mutagenic  or  toxic  for  the 

classification 
CLP 
triggers 
provisions 
under  many  pieces  of 

20 

 
 
 
 
 
 
 
 
Legislation 

Intervention logic 

ED identification 
provisions 

Hazard assessment of 
endocrine disrupting 
properties 

Provisions for management 
of substances with endocrine 
disrupting properties 

Main links with 
other legislation 

Packaging  of 
substances and 
mixtures  (EC) 
No 1272/2008 

  harmonised  hazard  classification 
as  cross-cutting  trigger  for  risk 
assessment  and/or  management  in 
other legislation  

  harmonised 

labelling 

and 
packaging  requirements  ensuring 
hazard 
along 
communication 
supply chain 

Persistent 
Organic 
Pollutants 
Regulation 
(EU) 
2019/1021 

Protects the environment from the risk 
posed by persistent organic pollutants 
by: 

  bans  and  restrictions  applicable  at 

 

international level 
reporting  data  on  uses  and 
environmental  monitoring 
to 
monitor  progress  and  promote 
awareness  

Food  contact 
materials 
legislation 
Regulation 
(EC) 
1935/2004  

No 

– 

Protects consumers and animals (feed 
Directive) 
to 
exposure 
from 
hazardous substances in food by: 

 

setting  rules  on  the  composition 
of  food  contact  materials,  mainly 
for 
an 
authorised  list  of  substances  and 
restrictions 

including 

plastics, 

the  criteria  of  other  hazard 
classes  (carcinogenic,  toxic 
specific 
reproduction, 
tor 
target 
– 
organ 
repeated exposure, etc). 

toxicity 

Reproduction (CMR) and other 
hazard  classes  triggers  hazard 
communication 
(labelling, 
packaging).  

legislation. 

No  

No 

specifically 

Criteria 
Persistent 
for 
Organic Pollutants (POPs) do 
address 
not 
endocrine 
disrupting 
properties, although they can 
be taken into account for the 
T-criterion (toxicity). 

a 

generic 

The  identification  as  POPs  is 
risk 
mainly 
approach  and 
triggers  ban 
and/or restrictions. Exemptions 
can  be  introduced  based  on 
risk-benefit considerations.  

disrupting 
Endocrine 
properties  are 
into 
account  as  other  hazards  in 
risk assessment 

taken 

Risk management of hazardous 
substances 
(authorisations, 
maximum  levels),  is  mainly  a 
specific risk approach. 

21 

Substances  used 
in 
food contact materials 
have  to  comply  with 
REACH 
registration 
provisions.  
Substances  identified 
SVHCs  with 
as 
endocrine  disrupting 
properties with effects 
on 
the  environment 
are subject to REACH 
authorisation 
provisions.  

 
 
 
 
 
 
Legislation 

Intervention logic 

ED identification 
provisions 

Hazard assessment of 
endocrine disrupting 
properties 

Provisions for management 
of substances with endocrine 
disrupting properties 

Main links with 
other legislation 

with 
Substances 
endocrine  disrupting 
properties with effects 
on  human  health  or 
the  environment  can 
restricted  under 
be 
REACH. 

Contaminants 
food 
in 
Regulation 
315/93/EEC 
and  in  animal 
feed  Directive 
2002/32/EC 

Food 
Additives  and 
food  enzymes 
and 
food 
flavourings, 
Regulation 
No 
(EC) 
1333/2008 and 
Regulation 
(EC) 
1331/2008 

No 

 

establishing  maximum  levels  or 
maximum  tolerances  for  certain 
contaminants  in  food  and  animal 
feed 

a 

  establishing 

common 
authorisation  procedure  for  food 
additives,  food  enzymes  and  food 
flavourings  by  including  also  data 
required for safety assessment 

Cosmetic 
Products 
Regulation 
(EC) 
1223/2009 

No 

Protects  consumers  from  exposure  to 
hazardous  chemicals 
in  cosmetic 
products by  regulating  the  placing on 
the  market 
two  main 
through 
channels:     

No 

taken 

disrupting 
Endocrine 
properties  are 
into 
account  as  other  hazards  in 
the  context  of  the  product-
level  safety  report  or  by  the 
SCCS. 

Generic  risk  approach  to  the 
extent 
that  some  hazardous 
substances  (e.g.  CMRs)  are 
banned,  with  limited  options 
for  derogations.  Specific  risk 
approach for other substances.  

in 
Substances  used 
cosmetic 
products 
have  to  be  registered 
under REACH.  
Substances  identified 
SVHCs  with 
as 

22 

 
 
 
 
Legislation 

Intervention logic 

ED identification 
provisions 

Hazard assessment of 
endocrine disrupting 
properties 

Provisions for management 
of substances with endocrine 
disrupting properties 

Main links with 
other legislation 

  all  substances  are  assessed  by 
industry 
through  product-level 
safety  assessment  reports.  These 
may  be  assessed  by  the  Scientific 
Committee  on  Consumer  Safety 
(SCCS)  and  managed  by 
the 
Commission when safety concerns 
are identified. 

  certain  groups  of 

substances 
considered  of  higher  hazard 
potential 
(colourants, 
preservatives,  UV  filters)  must  be 
assessed  for  safety  by  the  SCCS 
and  are  managed  through  lists  of 
approved ingredients. 

Protects  patient  users  and,  where 
appropriate,  other  persons 
from 
exposure  to  hazardous  chemicals  in 
medical devices by: 

  setting 

general 

safety 

requirements 

performance 
medical  devices  and 
diagnostics 

and 
for 
in  vitro 

  ensuring 

the 

that 

relevant 
scientific  opinions  of  the  relevant 
scientific  committees  are  taken 
into account 

endocrine  disrupting 
properties with effects 
on 
the  environment 
are subject to REACH 
authorisation 
provisions  and can be 
restricted 
under 
REACH. 

ED 
identification 
refers  to  REACH  and 
(for  medical  devices 
only) 
to  Biocidal 
Products  Regulation.  
in 
Substances  used 
medical  devices  have 
to  be registered under 
REACH.  
Substances  identified 
SVHCs  with 
as 
endocrine  disrupting 
properties with effects 
on 
the  environment 
are subject to REACH 
authorisation 
provisions.  

Presence  of  EDs  must  be 
justified  and  approvals  are 
based on risk-benefit. 

No  

from 

endocrine 
Hazards 
disrupting 
are 
taken  into  account  in  risk 
assessments. 

properties 

23 

Regulation 
(EU) 
2017/745  on 
medical 
devices 

Regulation 
(EU) 
2017/746  on 
in 
vitro 
diagnostic 
medical 
devices 

 
 
  
 
Legislation 

Intervention logic 

ED identification 
provisions 

Hazard assessment of 
endocrine disrupting 
properties 

Provisions for management 
of substances with endocrine 
disrupting properties 

Main links with 
other legislation 

Safety 

Toy 
Directive 
2009/48/EC 

Protects children from the exposure to 
hazardous chemicals in toys by: 

  prohibiting  the  use  of  substances 
which 
are 
Carcinogenic, 
the 
Mutagenic  or 
for 
Reproduction  (CMR)  with  limited 
possibilities for derogation 

toxic 

chemical 
in 

  establishing  specific  limit  values 
(including 
any 
for 
identified  EDs) 
for 
toys 
children  under  36  months  of  age 
and for toys intended to be placed 
in the mouth 

No 

Fertilising 
Products 
Regulation 
(EU) 
2019/1009 

Protects  human,  animal  and  plant 
health, safety and the environment by: 

 

the  placing  on 

regulating 
the 
market  of  chemicals  in  fertilising 
products  

No 

from 

endocrine 
Hazards 
disrupting 
are 
taken  into  account  as  other 
hazards. 

properties 

Combination  of  generic  risk 
(CMRs 
in 
principle)  and  specific  risk 
approaches (limit values). 

banned 

are 

from 

Hazards 
endocrine 
are 
disrupting 
taken  into  account  as  other 
hazards. 

properties 

Specific risk approach 

with 
Substances 
endocrine  properties 
with effects on human 
health 
the 
environment  can  be 
under 
restricted 
REACH. 

or 

All substances used in 
toys  have  to  comply 
with  provisions  under 
REACH.  Provisions 
registration, 
for 
and 
authorisations 
restrictions apply. 

All substances used in 
fertilising 
products 
have  to  comply  with 
under 
provisions 
REACH.  Provisions 
registration, 
for 
authorisations 
and 
restrictions apply. 

Detergents 

Achieves 

the 

free  movement  of  No 

Not applicable 

Not applicable  

Substances  used 

in 

24 

 
 
 
Legislation 

Intervention logic 

ED identification 
provisions 

Hazard assessment of 
endocrine disrupting 
properties 

Provisions for management 
of substances with endocrine 
disrupting properties 

Main links with 
other legislation 

Regulation 
(648/2004/EC) 

detergents  while,  at  the  same  time, 
ensuring  a  high  degree  of  protection 
of the environment and human health 
by: 

 

 

the  placing  on 

the 
regulating 
market of surfactants in detergents 
based 
biodegradability 
standards and phosphorus content 
labelling detergents 

on 

for 

Medicinal 
products 
humans 
(Directive 
2001/83/CE)15 

Main emphasis on the therapeutic 
benefit for the target group evaluated 
in the context of possible adverse side 
effects and risks to patients. 
Provisions are in place to evaluate and 
minimise the unintended effects of 
medicinal products via the 
environment by: 

 

environmental 

requiring 
risk 
assessment  and  risk  mitigation 
for  endocrine  active 
measures 
substances  

No16  

Regulation 
(EU)  2019/6 
on  veterinary 
medicinal 

Main  emphasis  on  the  therapeutic 
benefit  for  the  target  group  evaluated 
in the context of possible adverse side 
effects  and  risks  to  target  organisms 

No 

Endocrine 
disrupting 
properties  not  specifically 
addressed. 

detergents  are  also 
via 
regulated 
REACH, 
Biocidal 
Products  Regulation 
and 
the  Cosmetic 
Products  Regulation. 
under 
Provisions 
those 
regulations 
apply. 

Risk-benefit  approach.  The 
outcome  of  the  environmental 
assessment  does  not 
risk 
influence 
the  approval  of 
human  medicines  but  can 
trigger  measures  to  minimise 
exposure  (e.g.  communication, 
monitoring).  

Risk-benefit 
approach. 
Evidence  of  an  environmental 
be 
risk,  which 
risk 
controlled 

cannot 

with 

15In scope of this fitness check with respect to unintended exposure via the environment 
16Identification and assessment of endocrine active substances considered in ongoing revision of guidance for environmental risk assessment 

25 

 
 
 
 
 
 
                                                      
Legislation 

Intervention logic 

products15 

(treated animals).  

ED identification 
provisions 

Hazard assessment of 
endocrine disrupting 
properties 

Provisions for management 
of substances with endocrine 
disrupting properties 

Main links with 
other legislation 

Evaluates and minimises the 
unintended effects of veterinary 
medicinal products via the 
environment by: 

 

environmental 

risk 
requiring 
assessment 
establishing 
and 
approval  procedures  considering 
environmental risks 

Protects  consumers  health  and  safety 
by  requiring  that  only  safe  products 
are placed on the market: 

 

 

information 
rapid  exchange  of 
on 
states 
between  member 
taken  against  unsafe 
measures 
products  found  on 
the  market 
through  the  Rapid  Alert  System 
for  dangerous  non-food  products 
(Safety Gate/RAPEX) 
follow  up  risk  management  (e.g. 
market withdrawal) 

No. 
not 
Does 
include  provisions 
hazard 
for 
identification. 

and 

Water  legislation  collectively  aims  at 
enhancing  water 
protecting 
to  achieve  good  water 
resources 
quality.  This 
the  good 
chemical  and  ecological  status  of 
European  surface  waters,  the  good 
chemical  and  quantitative  status  of 
good 
and 
groundwater 

includes 

the 

given 

the 
to 
priority 

Yes, 
obligation 
identify 
(hazardous) 
substances under the 
Water  Framework 
Directive 
(WFD) 
(including 

properties 

The  assessment  of  endocrine 
of 
disrupting 
candidate 
priority 
(hazardous)  substances  takes 
assessments 
other 
legislation  into  account,  if 
available.  When  necessary 
(e.g.  for  substances  in  waste 

under 

26 

General 
Product Safety 
Directive 
(2001/95/EC) 

Water 
Framework 
Directive 
(2000/60/EC)  

Priority 
substances 
Directive 

management/mitigation 
measures,  can  prevent 
the 
granting of the authorisation, if 
the 
to 
outweigh  the  benefits  of  the 
product.  

is  considered 

risk 

on 

Identified  EDs  are  included  in 
market  surveillance  activities 
based 
restrictions 
established  in  other  legislation 
(e.g.  REACH),  or  by  evidence 
of  risk  (so  far  not  the  case  for 
EDs).  

Refers to the chemical 
legislation  for  hazard 
risk 
generic 
and 
assessment. 

Chemicals  can  be  prioritised 
for  monitoring  and  for  risk 
mitigation measures based on a 
combination  of generic  risk 
approaches (including 
endocrine  disrupting  hazard 
properties)  and specific  risk 
approaches. 

The  identification  of 
(hazardous) 
priority 
substances  considers 
the 
of 
selection 
substances  of  concern 
the 
undertaken 
relevant 
legislation 
regarding  hazardous 

in 

 
 
 
 
Legislation 

Intervention logic 

ED identification 
provisions 

Hazard assessment of 
endocrine disrupting 
properties 

Provisions for management 
of substances with endocrine 
disrupting properties 

Main links with 
other legislation 

(39/2013/EC) 

status 
environmental 
waters. It does this by: 

of  marine 

 

identifying  substances  of  concern 
and setting quality standards 
  coordinating  monitoring 

and 
reporting  of  priority  substances 
and other pollutants at EU level 
requiring  Member  States 
to 
identify  pollutants  of  national 
concern 
requiring  the  implementation  of 
risk  management  measures 
to 
reduce risks, including through the 
implementation  of  adequate  waste 
and drinking water treatment 

 

 

Drinking 
Water 
Directive 
(98/83/EC)  

Groundwater 
Directive 
(2006/118/EC) 

Marine 
Strategy 
Framework 
Directive 
(Directive 
2008/56/EC) 

Urban  Waste 
Water 
Directive 
(91/271/EEC) 

Chemical 
Agents 
Directive 
Work 
(98/24/EC) 

Carcinogens 
and  Mutagens 
Work 
at 
Directive 

Protect  safety  and  health  of  workers 
from  risks  arising,  or  likely  to  arise, 
from 
effects  of  hazardous 
substances at work by: 

the 

at 

 

taking  preventing  measures  and 
proposing 
and/or 
binding  occupational  exposure 
limit values 
  encouraging 

indicative 

necessary 

all 

of 

that 
substances 
are toxic,  persistent 
and  liable  to  bio-
accumulate and 
“substances 
equivalent 
concern”),  and  the 
inclusion 
of 
endocrine disrupting 
the 
substances 
in 
indicative 
list  of 
main pollutants. 

No 

or  transformation  products) 
assessments  are  carried  out 
considering evidence 
regarding the intrinsic hazard 
of the substance concerned. 

and 

This  is  the  case  for  priority 
substances 
priority 
hazardous substances under the 
substances 
WFD and 
for 
of endocrine 
representative 
the 
disrupting  effects under 
Drinking Water Directive. 

(e.g. 
substances 
REACH  or  PPPR  or 
BPR) 
relevant 
or 
international 
agreements 

Non ED-specific. 

risk 

Combination  of  generic  and 
approaches, 
specific 
a  hierarchy  of 
following 
from 
measures 
preventing 
to 
reducing  it  to  the  lowest  level 
for 
technically 
hazardous  chemicals  such  as 

going 
exposure 

possible 

from 

endocrine 
Hazards 
disrupting 
are 
taken  into  account  as  other 
hazards. 

properties 

27 

to 

Refers 
Classification 
and 
Labelling 
(CLP) 
Packaging 
hazard 
for 
hazard identification. 

classes 

 
 
  
 
 
  
Legislation 

Intervention logic 

ED identification 
provisions 

Hazard assessment of 
endocrine disrupting 
properties 

Provisions for management 
of substances with endocrine 
disrupting properties 

Main links with 
other legislation 

(2004/37/EC) 

Pregnant 
Workers 
Directive 
(92/85/EEC) 

Young  People 
Work 
at 
Directive 
(94/33/EC) 

measures  to  adjust  temporally  the 
working  conditions  of  pregnant, 
recently 
or 
breastfeeding workers 

given 

birth 

  prohibiting 

the  employment  of 
young  workers  (under  18)  if  it 
entails  exposure  to  agents  which 
are 
toxic,  carcinogenic,  cause 
heritable genetic damage, or harm 
to  the  unborn  child  or  which  in 
any  other  way  chronically  affect 
human health. 

Directive 
2008/98/EC 
on waste 

Protection  of  human  health  and  the 
environment  against  harmful  effects 
caused by waste by:  

rules 

  establishing 
for  waste 
management 
covering  waste 
hierarchy,  requirements  for  waste 
treatment,  waste  traceability  and 
end-of-waste.  Stricter  rules  apply 
for hazardous waste 

No  

Not applicable 

carcinogens,  mutagens 
reprotoxicants.  

or 

of 

risk 

approach. 
Generic 
Management 
waste 
including hazardous substances 
is  done  through  classification 
waste. 
hazardous 
of 
Notification 
hazardous 
of 
substances  in  material  streams 
based  on  REACH  listing  of 
Substances  of  Very  High 
(including  SVHCs 
Concern 
with 
disrupting 
properties). 

endocrine 

of 
Notification 
SVHCs 
in  articles 
indirectly  takes  into 
account 
endocrine 
disrupting  properties 
a 
to 
substance  has  been 
identified  as  SVHC 
under REACH.  

extent 

the 

Definition 
hazardous 
refers 
Classification 
Labelling 
Packaging 
hazard classes. 

of 
waste 
to 

and 
(CLP) 

Restriction  of 
of 
use 
the 

to 

the  protection  of 
Contributes 
human  health  and  the  environment 
sound 
environmentally 
through 

No 

Not applicable 

28 

Specific risk approach. Risk-
benefit  considerations  apply. 
Substances  to  be  regulated  are 

Substances  identified 
as 
SVHCs  with 
endocrine  disrupting 

 
 
 
Legislation 

Intervention logic 

ED identification 
provisions 

Hazard assessment of 
endocrine disrupting 
properties 

Provisions for management 
of substances with endocrine 
disrupting properties 

Main links with 
other legislation 

certain 
hazardous 
substances 
in 
electrical  and 
electronic 
equipment 
(Directive 
2011/65/EU) 

Industrial 
emissions 
(integrated 
pollution 
prevention and 
control) 
Directive 
(2010/75/EU) 

Seveso-III-
Directive 
(2012/18/EU) 

recovery  and  disposal  of  waste 
electrical  and  electronic  equipment 
by: 

 

restricting 
hazardous substances 

the  use  of  certain 

Aims at environmental protection and 
improvement 
environmental 
of 
quality by: 

their 
identified  based  on 
impact  on  waste 
negative 
recycling, 
treatment 
potential 
for  environmental 
and  worker  exposure  and 
replacement options.  

and 

properties  and  which 
have  been  added  to 
the 
REACH 
authorisation  list,  as 
well  as 
substances 
restricted 
are 
that 
under REACH can be 
for 
considered 
restrictions 
under 
RoHS. 

  setting  rules  to  prevent  or  to 
reduce  emissions  into  air,  water 
and 
the 
land  and 
generation of waste  
requiring  the  application  of  Best 
Available  Techniques  (BAT)  in 
installations.  

to  prevent 

 

Protection  of  human  health  and  the 
environment by: 

  setting  rules  to  prevent  major-
involving  dangerous 

accidents 
substances 
  provisions 

to 
consequences of such accidents 

limit 

the 

No. 
not 
Does 
include  provisions 
for 
hazard 
identification. 

Not applicable 

Emission  limit  values  set  in 
this  directive  are  based  on  the 
BAT,  not  on 
(eco)toxicity 
criteria. 

Defines 

based 
certain 

No. 
"dangerous 
substances" 
on 
Classification 
and 
Labelling 
Packaging 
(CLP) 
hazard  classes  and 
volume. 

Not applicable 

Mainly generic risk approach 
with  consideration  of  potential 
exposure. 

29 

 
 
 
 
 
Legislation 

Intervention logic 

ED identification 
provisions 

Hazard assessment of 
endocrine disrupting 
properties 

Provisions for management 
of substances with endocrine 
disrupting properties 

Main links with 
other legislation 

Directive 
2008/50/EC 
on  ambient  air 
quality 
and 
cleaner  air  for 
Europe;  

Protection  of  human  health  and  the 
environment by: 

  monitoring  air  quality  against 
established  air  quality  standards 
allowed 
(i.e. 
concentrations) 
taking  measures 
compliance 

maximum 

ensure 

to 

 

to 

Directive 
2004/107/EC 
relating 
arsenic, 
cadmium, 
mercury, 
nickel 
polycyclic 
aromatic 
hydrocarbons 
in ambient air. 

and 

No 

Not applicable 

The  determination  of  quality 
standards  follows  a  specific 
risk approach. 

is 

not 
Ecolabel 
awarded 
to  goods 
containing  inter  alia 
identified 
substances 
as 
under  REACH 
SVHCs 
with 
endocrine  disrupting 
properties. 

Regulation 
No 
(EC) 
66/2010 on the 
EU Ecolabel 

Promotes  products 
services 
meeting high environmental standards 
throughout their life-cycle by: 

and 

No  

Not applicable 

 

implementing 
labelling scheme (ecolabel) 

a 

voluntary 

The Ecolabel criteria are based 
on  hazards 
risk 
approach).  

(generic 

is 

not 
Ecolabel 
awarded 
to  goods 
containing  inter  alia 
identified 
substances 
under  REACH 
as 
SVHCs  with  ED 
properties. 

30 

 
 
 
 
 
 
4  COHERENCE 

  The World Health Organization definition of endocrine disruptors is broadly accepted in EU 
legislation.  The  criteria  for  the  identification  of  EDs  under  the  Plant  Protection  Products 
Regulation and Biocidal Products Regulation, and as substances of very high concern under 
REACH,  are  based  on  this  definition.  EU  Agencies  (EFSA,  ECHA)  and  the  Commission’s 
Scientific Committee on Consumer Safety (SCCS) have endorsed the definition and apply it 
in the assessment of EDs.  

  Differences  in  data  requirements  reflect  different  exposure  scenarios  contributing  to  risk, 
socioeconomic  proportionality  and  laboratory  animal  welfare  considerations.  Following  the 
establishment of criteria for the identification of endocrine disruptors, data requirements are 
being  updated  for  plant  protection  products  and  biocidal  products.  The  data  requirements 
under REACH are also being updated. Ready access to the data eventually generated would 
also be helpful in other policy areas that have provisions for ensuring the safety of  products 
placed on the EU market, but no specific data requirements. 

  Further work is required to fulfil the Commission’s ambition of a horizontal approach to the 
identification of ED, which is a gap criticised by many stakeholders. It creates uncertainty and 
confusion  about  the  consequences  across  legislation.  Most  stakeholders  favour  a  horizontal 
approach to identification. Based on the limited number of cases to date, there is no evidence 
of  inconsistent  identification  across  the  regulations  currently  requiring  the  identification  of 
EDs (mainly BPR, PPPR and REACH). 

  Currently there is no hazard class for endocrine disrupting properties under the Classification 
Labelling  and  Packaging  (CLP)  Regulation.  Identification  of  a  Carcinogenic,  Mutagenic  or 
toxic for Reproduction (CMR) substance as an ED for human health will probably not lead to 
any  additional  risk  management  measures,  where  they  are  already  the  strictest  but  may 
nevertheless contribute to the overall evaluation within a risk-benefit context. In addition, not 
all  EDs  for  human  health  will  be  identified  as  CMRs  and  identification  as  an  ED  for  the 
environment may also trigger additional risk management measures. 

  There  are  different  opinions  among  authorities  and  experts  about  the  ability  to  demonstrate 
safe  or  unsafe  uses  of  EDs  using  available  methods  in  a  risk  assessment.  The  lack  of 
consensus underlines the crucial role of the European Commission, its scientific committees 
and  EU  agencies  to  ensure  alignment  of  assessment  approaches  and  coordination  of 
subsequent  risk  management.  At  EU  level,  agencies  and  scientific  committees  may  in 
principle conclude on a level below which no risk is identified, if the evidence for a specific 
substance allows a threshold to be established. However, it is still debated which evidence and 
methods  allow  the  establishment  of  a  threshold  below  which  no  significant  risk  is  expected 
for endocrine disruption. 

  There  are  few  examples  of  risk  assessments  based  on  endocrine  disrupting  properties.  For 
DEHP  (and  other  phthalates),  both  ECHA  and  EFSA  concluded  based  on  an  exceeded  safe 
threshold  for  anti-androgenic  mediated 
to  male  reproduction.  Octylphenol, 
nonylphenol  and  their  ethoxylates  were  identified  as  Substance  of  Very  High  Concern 
(SVHC)  because  of  endocrine  disrupting  properties  in  the  environment.  In  the  case  of  the 
restriction  of  certain  uses  of  these  substances,  ECHA’s  Risk  Assessment  Committee 

toxicity 

31 

 
 
 
considered  that  effects  from  endocrine  disruption  could  occur  below  the  predicted  no  effect 
concentrations derived for other endpoints. However, risks were identified following standard 
risk  assessment  applied  to  non-ED  specific  endpoints,  which  was  sufficient  to  justify  the 
restriction. The uncertainties associated with the possible peculiarities of endocrine disrupting 
effects (i.e. non-threshold, non-monotonic behaviour) are recognised and in some cases have 
been  taken  into  account  through  the  use  of  uncertainty  factors,  defined  on  a  case  by  case 
basis. 

  There is an opportunity to introduce or improve the consistency of definitions of vulnerable 
groups  across  legislation  and  to  clarify  the  scientific  rationale  (degree  of  exposure  or 
biological  susceptibility)  for  triggering  specific  provisions  for  vulnerable  groups.  In  the 
meantime,  some  flexibility  in  the  consideration  of  vulnerable  groups  (definitions,  relevant 
hazard  endpoints,  data  requirements)  will  be  needed  to  adapt  the  methodology  currently  in 
use. 

  Different  approaches  to  risk  management  (e.g.  generic  risk  approaches  vs  specific  risk 
approaches  vs  risk-benefit  approaches)  are  pragmatic  approaches  reflecting  policy-specific 
considerations.  This  situation  has  been  criticised  by  many  stakeholders,  who  expressed 
concern  that  differences  in  risk  management  measures  may  not  be  justified.  Indeed,  the 
rationale  for  some  of  the  differences  should  be  made  more  transparent.  Based  on  a  limited 
number  of  examples  this  Fitness  Check  found  no  cases  of  inconsistent  risk  management  of 
specific substances caused by ED-specific issues.  

  The  difficulty  in  choosing  a  risk  management  approach  is  partly  related  to  the  fundamental 
scientific  question  of  whether  EDs  are  (all)  threshold  or  non-threshold  substances.  In  the 
absence  of  scientific  consensus,  legislation  can  either  opt  for  an  approach  that  does  not 
require  an  answer  to  the  question  (e.g.  generic  risk  approach  with  derogations  as  done  for 
plant protection products and biocidal products) or it can determine case by case whether or 
not a safe (or acceptable) threshold can be quantified and consequently apply an appropriate 
risk  management  approach,  as  done  in  REACH.  Certain  pieces  of  sectorial  legislation  (e.g. 
Cosmetic  Products  Regulation,  Food  Contact  Materials  Regulation)  not  only  lack  specific 
provisions  for  assessing  EDs  but  also  lack  specific  guidance  on  how  to  deal  with  EDs  for 
which it is not possible to quantify a safe (or acceptable) threshold. In practice, in cases where 
a threshold cannot be established the regulatory approach followed under EU legislation is to 
minimise exposure as far as possible, including the option to prohibit the use of a substance. 
Options for consolidation compatible with the Commission’s ambition of “one substance one 
assessment” should therefore be explored. 

  The  current  regulatory  frameworks  for  different  products  do  not  provide  a  comprehensive 
framework  for  integrated  exposure  assessment  across  sectors  and  material  life  cycles  as  a 
basis  for  an  overarching  risk  assessment  and  subsequent  coordinated  intervention.  This  has 
led to differences in the extent of risk management when the same (group of) substances, such 
as phthalates including DEHP, have been assessed under different regulatory frameworks.  

  When  judged  from  a  broader  health  and  environmental  protection  perspective,  the  inherent 
complexity  of  the  legislative  framework  for  chemical  risk  assessment  and  management  is  a 
challenge  to  systematic  and  harmonised  consideration  of  aggregate  and  combined  exposure 
scenarios.  

  Lack  of  coordination  between  chemical,  product,  water  and  waste  legislation  (e.g.  safety  vs 
recyclability  targets,  or  cessation  of  emissions  to  water)  has  a  negative  impact  on 

32 

 
 
effectiveness and efficiency. Sector-specific approaches to identification and management of 
EDs cannot be effective for the identification and management of EDs in waste streams (e.g. 
consumer  products  ending  in  municipal  waste),  except  in  cases  where  material  streams  are 
collected and managed separately.  

  The EU regulatory system is the only one worldwide that has implemented scientific criteria 
to define EDs in legislation. The implementation of a generic risk approach to regulate EDs in 
plant  protection  products  and  biocidal  products  has  been  frequently  criticised  by  WTO 
members. 

Q1  –  To  what  extent  are  the  different  provisions  on  and  approaches  to  endocrine  disruptors 
coherent  across  regulatory  areas  (e.g.  horizontal  legislation  on  chemicals,  sector-specific  and 
media-related legislation)? 

4.1

  Data requirements  

Data  requirements  (sometimes  known  as  information  requirements)  are  legal  obligations  placed  on 
manufacturers or importers to generate data, such as results from toxicity tests, and to provide them to 
authorities. Establishing data requirements in legislation requires balancing the need for information 
on the (eco-)toxicological properties of substances with the burden on economic operators and with 
animal welfare considerations. Provisions should also avoid multiple generation of data for the same 
substance subject to different pieces of legislation. 

Some  regulations  such  as  the  Biocidal  Products  Regulation  and  the  Plant  Protection  Products 
Regulation, require comprehensive data sets, justified by substances used in those sectors purposely 
being  designed  to  be  biologically  active  and/or  with  potential  high  exposure  to  humans  or  the 
environment.  The  general  legislation  on  chemicals  (REACH)  obliges  the  registrant  to  register 
substances  and  to  provide  data  as  set  out  in  the  REACH  annexes  on  standard  information 
requirements with increasing requirements according to the production volume for all substances on 
their own or in mixtures (and in some cases also for articles) manufactured or placed on the market 
unless there is an exemption. Inter alia, substances manufactured or imported in low quantities (< 1 
tonne per year) or polymers do not require a registration. The obligation to register does not apply to 
active  substances,  safeners  and  synergists  used  in  plant  protection  products,  as  active  substances  in 
biocidal  products,  in  medicinal  products  for  human  or  veterinary  use,  or  substances  intentionally 
added to food and animal feed. Chemical substances used in other sectors such as toys, food contact 
materials  or  cosmetic  products  are  not  exempted  from  the  obligation  to  register  and  provide  data 
under  REACH.  Other  legislation  such  as  the  Cosmetic  Products  Regulation  (CPR)  and  the  Food 
Contact  Material  (FCM)  Regulation  require  further  information  that  are  specific  for  the  products  or 
the sector they regulate. 

In general, further provisions are in place (such as the substance evaluation procedure under REACH) 
to request further data if a concern arises that is not covered with the standard obligations.  

Legislation with no or limited obligations to generate (eco-)toxicological data (such as toys, medical 
devices  or  environmental  legislation)  uses  all  available  scientifically  sound  data  for  assessing  risks, 
such  as  data  generated  under  other  regulations,  data  from  academic  literature  or  data  supplied 
voluntarily at the initiative of the industry parties concerned. 

33 

 
 
 
The  recent  fitness  check  on  the  EU  chemicals  legislation  concluded  that  differences  in  data 
requirements “can for the most part, be explained and justified on the grounds of differing likelihood 
of  exposures  (risks),  of  costs  and  proportionality  and  of  laboratory  animal  welfare  considerations. 
Differences are mostly justified and do not seem to lead to major incoherence issues”17. This overall 
conclusion can also be regarded as applicable to the data requirements for the evaluation of endocrine 
disrupting  properties.  However,  it  should  be  recognised  that  these  differences  are  policy  decisions 
driven by proportionality balancing costs and animal welfare against generic exposure considerations.   

Provisions for the generation of toxicological data related to chemicals or products that can inform on 
endocrine-mediated  effects  on  human  health  are  included  in  the  legislation  on  plant  protection 
products,  biocidal  products,  REACH,  food  contact  materials,  food  additives,  cosmetics  and 
pharmaceuticals. Provisions for the generation of ecotoxicological data that can inform on endocrine-
mediated  effects  on  wildlife  are  included  in  the  legislation  on  plant  protection  products,  biocidal 
products, REACH and pharmaceuticals. At present, data requirements under these regulations focus 
primarily on  in vivo repeated  dose, reproductive or developmental toxicity testing in mammals, and 
tests with aquatic (or terrestrial) organisms, providing data on adverse effects. Further investigations 
to confirm an endocrine mode of action are triggered based on observations of potentially endocrine-
mediated  adverse  effects  from  these  tests.  Specific  in  vitro  or  in  vivo  tests  investigating  endocrine 
modes  of  action  (mechanistic  tests)  are  not  currently  part  of  the  standard  data  requirements.  The 
ongoing  revisions  of  standard  data  requirements  for  biocidal  products  and  plant  protection  products 
consider the inclusion of additional tests for endocrine properties as part of the core data set. Under 
REACH, work on incorporating further tests for endocrine properties has started. 

Legislation  and/or  regulatory  guidance  on  data  requirements  and  hazard  assessment  for  plant 
protection products, biocidal products, REACH, food contact materials, food additives and cosmetics 
refer to accepted international guidance such as OECD Test Guidelines (TGs). The TGs relevant for 
testing  of  EDs  are  grouped  in  the  OECD  Conceptual  Framework  for  Testing  and  Assessment  of 
Endocrine  Disrupters.  The  OECD  Guidance  Document  150  (which  includes  the  Conceptual 
Framework) provides guidance on the interpretation of the tests and suggestion on possible next steps 
in  testing  (OECD,  2018).  The  Conceptual  Framework  comprises  five  evidence  levels  listing  the 
OECD  TGs  and  standardised  tests  methods  available,  under  development  or  proposed,  that  can  be 
used to evaluate chemicals for endocrine disruption. Many of the in vivo TGs (at levels 4 & 5 of the 
Conceptual  Framework)  are  the  standard  toxicity  TGs  used  for  the  evaluation  of  toxicity  and 
ecotoxicity  in  general  and  are  not  specific  to  endocrine  disruption.  They  are  listed  because  they 
investigate  toxic  effects  that  may  be  endocrine-mediated.  Levels  2  &  3  list  the  methods  developed 
specifically  to  investigate  endocrine  modes  of  action  and  need  to  be  used  in  combination  with  the 
methods at levels 4 &5. Level 1 refers to existing data and non-test information (e.g. computational 
predictions). 

Data  generated  using  OECD  TGs  are  subject  to  Mutual  Acceptance  of  Data  (MAD),  allowing  data 
generated in one OECD Member Country to be accepted by all OECD Member Countries as well as 
other  adherents  to  MAD,  thus  removing  the  need  for  repetition  of  tests  when  seeking  regulatory 
approvals  across  different  global  regions.  EU  regulations  generally  require  consideration  of  all 
available information, i.e. not only data from accepted international guidelines, but also data coming 
e.g. from peer-reviewed literature. 

17COM (2019) 264, p79 

34 

 
 
                                                      
For active substances regulated under the Plant Protection Products Regulation (PPPR), EDs can be 
identified based on level 4 and 5 tests from the Conceptual Framework (i.e. in vivo assays providing 
data  on  adverse  effects  on  endocrine  relevant  endpoints,  and  in  vivo  assays  providing  more 
comprehensive data on adverse effects on endocrine relevant endpoints over more extensive parts of 
the life cycle of the organism) which are required for human health assessments. Some mechanistic 
tests, informing on specific endocrine modes of action can be triggered, namely the uterotrophic assay 
(OECD TG 440), the Hershberger assay (OECD TG 441), or the  in vitro assays for the detection of 
estrogenic  activity  and  measurement  of  steroidogenesis  (OECD  TG  455  and  456).  For  non-target 
organisms, data required are mainly based on level 3 and level 4 fish and amphibian tests. The data 
requirements  for  active  substances  and  plant  protection  products  are  described  in  Regulations  (EU) 
the  accompanying  Commission 
No  283/2013  and  (EU)  No  284/2013,  respectively,  and 
Communications (2013/C 95/01 and 2013/C 95/02). 

For biocidal products, tests required for human health safety assessment in Annexes II and III to the 
Biocidal  Products  Regulation  (BPR)  are  similar  to  the  ones  required  for  plant  protection  products, 
with mechanistic studies being also only triggered on the basis of observations in in vivo tests. For the 
ecotoxicological assessment however, data requirements listed  in  the Annexes are less specific than 
for  plant  protection  products.  However,  the  BPR  requires  applicants  to  provide  the  relevant 
information necessary to carry out the evaluation.  

For  these  two  Regulations  (PPPR  and  BPR),  a  joint  guidance  document  ‘Guidance  for  the 
identification of endocrine disruptors in the context of Regulations (EU) No 528/2012 and (EC) No 
1107/2009’ (ECHA et al., 2018) describes which information should be provided in order to conclude 
on the potential endocrine disrupting properties of a substance. 

Under REACH, standard information requirements depend on the tonnage manufactured or imported 
(Annex  VII  to  Annex  X).  Further  tests  can  also  be  triggered  by  conditions  listed  in  column  218. 
However,  the  REACH  substance  evaluation  process  offers  the  possibility  to  require  registrants  to 
submit  data  derived  with  an  accepted  test  method  that  is  not  listed  in  the  standard  information 
requirements,  if  there  is  a  specific  concern  such  as  endocrine  disruption.  To  date,  “endocrine 
disruption” was a concern mentioned for launching this procedure in more than 80 cases. The need to 
align  the  framework  with  the  newly  established  criteria  under  the  PPP  and  BP  Regulations  and  the 
latest  methods  available  has  been  recognised.  The  process  has  been  initiated  within  a  REACH 
CARACAL subgroup, which met for the first time in February 2020. 

Substances in food contact materials (FCM) for which an authorised list has been established in the 
framework of the Regulation (EC) no 1935/2004, such as plastics, are assessed by the European Food 
Safety  Authority  (EFSA)  in  accordance  with  its  own  Note  for  Guidance  (EFSA  Panel  on  Food 
Contact  Materials  et  al.,  2008).  This  EFSA  Note  sets  out  the  data  requirements  for  the  safety 
assessment  based  on  the  migration  of the  substances  from  the  plastic  food  contact  material  into  the 
food.  As  a  general  principle,  the  greater  the  exposure  through  migration,  the  more  toxicological 
information is required. Although there are no specific provisions for EDs in the FCM legislation, in 
the case of plastic FCM, where migration is relatively high (i.e. migration 5–60 mg/kg food) studies 
investigating  reproductive  and  developmental  toxicity  are  required  (EFSA  Panel  on  Food  Contact 
Materials  et  al.,  2008).  Business  operators  using  substances  in  the  FCM  or  the  applicant  are  also 

18For example, effects observed in the screening study (OECD TG 421 or TG 422) may serve as triggers, 
leading to more comprehensive reproductive toxicity studies which in the case of suspected ED properties may 
trigger the request for an Extended One-Generation Reproductive Toxicity Study (EOGRTS) as well as 
consideration of inclusion of the developmental neurotoxicity and immunotoxicity cohorts 

35 

 
 
                                                      
required  to  inform  the  Commission  immediately  should  any  new  scientific  information  become 
available that may affect the authorisation. This could include changes in the migration or additional 
toxicological  information  e.g.  from  the  scientific  literature  or  new  data  available  under  REACH.  If 
necessary, further assessment by EFSA should be carried out. Moreover the EFSA scientific opinion 
on recent developments in the safety assessment of chemicals in food (EFSA Panel on Food Contact 
Materials  et  al.,  2016)  supports  consideration  of  additional  studies  on  specific  endpoints  including 
those  resulting  from  possible  endocrine  disruption    (as  from  OECD  GD150,  2012),  as  well  as 
immunotoxicity and neurotoxicity, regardless of the level of exposure. Regarding food additives, there 
are no specific provisions for EDs, however the repeat dose and reproductive/developmental testing 
methods  listed  in  the  EFSA  Guidance  for  submission  of  food  additive  evaluations  (EFSA  Panel  on 
Food Additives and Nutrient Sources added to Food, 2012) do include endocrine-relevant endpoints. 
Moreover, the guidance refers to other studies (in addition to the core areas for evaluation) that may 
be  relevant  and  useful  for  assessing  the  risk  and  establishing  the  safety  of  an  additive  include 
immunotoxicity,  hypersensitivity  and  food  intolerance,  neurotoxicity,  endocrine  activity  and 
mechanisms and modes of action. 

Substances  used  in  cosmetic  products  are  also  subject  to  the  registration  obligation  under  REACH, 
(based  on  the  tonnage  band),  and  thus  the  relevant  REACH  data  requirements  have  to  be  fulfilled. 
There are no explicit data requirements specified in the Cosmetic Products Regulation (CPR), which 
instead refers to the Scientific Committee for Consumer Safety’s Notes of Guidance  (SCCS, 2018). 
These  describe  the  types  of  data  that  may  be  used  or  generated  by  the  manufacturers  to  make  an 
assessment  for  each  toxicological  endpoint  relevant  to  human  health,  which  the  manufacturer  takes 
into account when there is a need to submit a safety dossier under the CPR authorisation procedures. 
Data relevant to endocrine modes of action may be provided through the assessment of reproductive 
toxicity or through special investigations on suspected endocrine disruptors for human health.  

developmental 

toxicity. Many 

The guidance refers to the OECD Conceptual Framework, however, due the ban on animal tests, only 
in silico and in vitro methods can be used to evaluate safety for human health, while data from in vivo 
studies may be used if they are already available or generated through other regulatory processes such 
as  under  the  PPPR,  the  BPR  and  REACH.  The  relevant  toxicological  studies  described  in  the 
guidance cover standard apical endpoints, including reproductive toxicity. For reproductive toxicity, 
three in vitro embryotoxicity screening tests have been validated by ECVAM to support assessment of 
reproductive  toxicity.  Overall,  the  complex  endpoint  of  reproductive  toxicity  is  not  covered  by  the 
above systems and no alternative methods are currently available covering all aspects of reproductive 
and 
on in 
vivo reproductive/developmental  toxicity  studies  (e.g.  OECD  TGs  416,  414,  421,  422  and  443) 
performed before the animal testing ban (e.g. Annex 5A - 3-BC case study). The guidance does not 
require tests addressing the four E-A-T-S modalities. Results from available in silico and in vitro tests 
for  endocrine  activity  do  not  fit  in  the  risk  assessment  framework  followed  by  the  SCCS  for  safety 
evaluations. In addition, according to the SCCS, such tests would only inform on endocrine activity 
but not adversity. According to the SCCS, the animal testing ban would not enable the identification 
of EDs according to the WHO definition or according to the criteria for biocides and pesticides, which 
require information on three elements, namely endocrine activity, adverse effect and plausible causal 
link.   However,  the  SCCS  recognises  the  need  to  transition  toward  an  animal-free  risk  assessment 
methodology,  sometimes  called  Next  Generation  Risk  Assessment  (NGRA).  However,  this  will 
require  methodological  developments  and  experience  in  the  application  and  interpretation  of  New 
Approach Methodologies (NAMs) (Rogiers et al., 2020). 

opinions 

SCCS 

recent 

relied 

have 

36 

 
 
The  combination  of  provisions  for  data  requirements  under  REACH  (tonnage-based)  and  the  CPR 
together with the incremental restrictions on animal testing over time explain the current differences 
in  data  packages  available  for  individual  substances.  For  some  cosmetic  ingredients  evaluated  and 
approved in the past, including substances listed in the annexes to the CPR (positive list of approved 
colourants, preservatives and UV-filters), data for the evaluation of endocrine-mediated effects can be 
very limited if the substance is not registered under REACH or registered at the lowest tonnage level 
(1 to 10 tonnes per year) (see also Annex 5A, 3-BC case study). In case the substance is not registered 
in REACH (i.e. not on the market in a tonnage of at least 1 t/y or above), there are no mechanisms to 
know if those substances on the positive lists continue to be used at all.   

In  addition  to  the  data  prescribed  to  ensure  therapeutic  efficacy and  safety  (not  in  the  scope  of  this 
Fitness Check), regulations on human and veterinary medicines include data requirements to evaluate 
potential  unintended  ecotoxicological  effects.  A  draft  guidance  by  the  European  Medicines  Agency 
(EMA)  on  the  environmental  risk  assessment  (ERA)  of  human  medicines  was  released  for  public 
consultation  in  201919  and  is  currently  under  revision.  According  to  this  draft  guidance,  testing  for 
endocrine active substances may be triggered as part of a tailored risk assessment for endocrine active 
substances (Annex 4). The draft Guidance published for public consultation lists recommended tests 
to address (anti)estrogenic, anti(androgenic) and thyroid effects (OECD TGs 234, 240, 241) Testing 
on  thyroid  agonist  or  antagonist  effects  is  recommended,  even  though  the  definition  of  endocrine 
active  substance  given  in  the  guidance  does  not  cover  the  thyroid  modality.  Discussions  on  the 
finalisation of the Guidance are ongoing. 

Guidelines  on  environmental  safety  assessments  for  non-target  organisms  of  veterinary  medicines 
refer  to  the  VICH  guidance  (EMA,  2000,  2005).  The  tiered  approach  consists  of  a  two-phase 
approach. Only when environmental exposure from the use of the veterinary medicine is considered to 
be  significant  (by  exceeding  established  threshold  values),  a  higher-tier  assessment  based  on  a  risk 
ratio will be triggered. This second phase will be conducted starting from basic risk assessments using 
short term (acute) toxicity to chronic aquatic toxicity studies with standard aquatic species from three 
trophic levels. Required studies do not include endpoints that are relevant and can identify endocrine-
mediated effects. The ability to identify potential EDs is limited to evidence from changes indicative 
of  endocrine  dysfunction  reported  in  the  mammalian  repeated  dose  toxicity  studies  (performed  to 
establish a maximum residue limit to ensure the safety of veterinary drug residues in human food) or 
to scientific literature. Such evidence may prompt the member state competent authority or EMA to 
request additional studies targeted to investigate ED properties. 

To conclude, ongoing revisions of standard data requirements for biocidal products, plant protection 
products and for REACH consider the inclusion of additional tests for endocrine properties as part of 
the mandatory data set .Currently test guidelines are only available to cover the estrogen, androgen, 
thyroid and steroidogenesis modalities (EATS) but this is likely to increase over time, as more OECD 
Test  Guidelines  covering  other  endocrine  modes  of  action  are  validated  and  adopted.  Since  many 
substances  used  in products  subject  to product-specific legislation  in the scope  of this fitness check 
are required to be registered under REACH, the information requirements in REACH can be used as a 
centralised way to gather the relevant data, thus avoiding repetition of studies on the same substance 
in other regulatory domains. In relation to arguments of proportionality of costs and considerations of 
animal welfare, when adopting REACH the co-legislators have chosen to use production volume of 
substances as a surrogate of exposure (and consequent risk) potential and thus substances produced at 

19https://www.ema.europa.eu/en/environmental-risk-assessment-medicinal-products-human-use#current-
version-section 

37 

 
 
                                                      
volumes  below  10  tonnes/producer/year  have  a  data  set  which  does  not  give  any  indications  of 
endocrine  disrupting  properties.  However,  all  available  information,  including  from  in  vitro  tests, 
QSARs  and  read-across  to  other  substances  has  to  be  taken  into  account  by  manufacturer  or 
importers.  The  OECD  GD  150  lists  several  in  vitro  tests  that  provide  information  on  endocrine 
activity. Currently, these in vitro tests are not a mandatory part of data requirements of the relevant 
regulations. Substances produced at less than 1 tonne/producer/year are currently not registered under 
REACH and thus it is important to be aware that REACH will not provide any data in these cases to 
support  ED  identification  for  such  substances  used  in  other  product-specific  legislation.  Legislation 
covering the food additives and food contact materials which has data requirements independent of, or 
additional  to  REACH,  respectively,  follows  a  similar  approach  whereby  concerns  for  endocrine 
disrupting activity may be identified from the required toxicity tests. Coordination is required between 
REACH and these regulations to avoid the duplication of testing and ensure the best use of resources.  

4.2

  Hazard identification 

4.2.1 

Identification of endocrine disruptors 

Three  EU  Regulations  contain  provisions  to  identify  EDs,  i.e.  the  Biocidal  Products  Regulation 
(BPR), the Plant Protection Products Regulation (PPPR) and REACH.  

Identification of active substances as endocrine disruptors is mandatory for plant protection products 
and  biocidal  products  (for  the  latter  also  non-active  substances  need  to  be  assessed),  following 
scientific criteria established in 2017 and 2018. It is pursued, to the extent possible, under REACH. It 
is not required in other sectors. The identification of EDs requires: i) a definition, ii) clear criteria to 
determine whether the definition is met, iii) data requirements to establish if criteria are met, and iv) 
guidance for implementation of the assessment process.  

Across chemical legislation, there is wide acceptance of the WHO definition: “an endocrine disruptor 
is an exogenous substance or mixture that alters function(s) of the endocrine system and consequently 
causes  adverse  health  effects  in  an  intact  organism,  or  its  progeny,  or  (sub)  populations”.  The 
definition  is  supported  by  most  stakeholders  ((European  Commission,  2015).  However,  differences 
exist in the wording used across regulations. Although all relevant provisions refer to ED properties, 
regulations vary in the emphasis on the adversity and causality attributes, as analysed in the Fitness 
Check  of  EU  chemicals  legislation  (excluding  REACH)20.  Differences  in  wording  might  create 
uncertainty  as  regards  which  chemicals  are  considered  EDs  by  the  legislative  provisions  and  what 
level of evidence is required to identify such chemicals.  

Criteria,  data  requirements  and  guidance  to  enable  the  identification  of  EDs  exist  for  the  Plant 
Protection Products and Biocidal Products Regulations. The European Chemical Agency (ECHA) and 
the European Food Safety Authority (EFSA) jointly published a guidance document (ECHA / EFSA 
2018) based on these criteria. The guidance has been recognised as a major milestone providing clear 
and  scientifically  sound  interpretation  of  the  WHO  definition  (PETI  Committee  for  the  European 
Parliament 2019). It provides a starting point for any future cross-sectorial definition of EDs. ECHA, 
EFSA and Member State authorities are sharing first experiences to ensure consistent application of 
the  guidance  and  to  identify  possible  improvements21.  The  Agencies  are  also  collaborating  on  ED 
assessments for specific substances of common interest.  

20SWD (2019) 199, Annex 7 p.302 
21Targeted consultation with ECHA and EFSA – May 2020. See also: 

38 

 
 
 
                                                      
 
Currently,  REACH  does  not  contain  criteria  for  EDs,  but  bases  the  identification  of  Substances  of 
Very High Concern (SVHCs) with ED properties on the IPCS/WHO definition. The identification of 
an  ED  as  SVHC  needs  also  to  consider  whether  the  effects  give  rise  to  an  “equivalent  level  of 
concern” to those of other SVHC categories. This assessment is done on a case-by-case basis. In case 
of  lack  of  consensus  in  the  REACH  Member  State  Committee,  the  Commission  takes  the  final 
decision through the REACH comitology process.  

The  Cosmetic  Products  Regulation  (CPR)  does  not  require  the  identification  of  EDs.  However, 
substances used in cosmetics, may be identified as EDs under REACH in relation to environmental 
concerns or, for substances that are registered for other uses, with respect to human health. According 
to the Scientific Committee on Consumer Safety (SCCS), it would not be feasible in the context of the 
animal testing ban to implement all the criteria established for plant protection products and biocidal 
products in the CPR, i.e. the requirement to demonstrate an adverse effect, which currently is mainly 
demonstrated through in vivo animal studies. The Commission can request the SCCS to evaluate the 
safety  of  substances  identified  as  potential  endocrine  disruptors  but  the  specific  risk  approach  that 
underpins  the  SCCS  safety  evaluations  does  not  depend  on  formal  identification  of  EDs  (SCCS 
2018).Error!  Bookmark  not  defined..
    Chemicals  used  in  medical  devices,  food  contact  materials,  cosmetic 
products, detergents and toys as well as in other sectors can in principle be identified as SVHCs with 
endocrine disrupting properties via REACH and therefore the absence of specific provisions  for ED 
identification in the sector-specific legislation does not necessarily represent a regulatory gap across 
legislation.  

Although  the  absence  of  horizontal  criteria  creates  a  potential  for  inconsistent  identification  across 
regulation,  which  is  further  compounded  through  different  data  requirements  and  different 
interpretations  of  the  same  data,  no  inconsistent  identification  has  occurred  so  far.  The  targeted 
stakeholder survey provided insights into the different views about the lack of a horizontal approach 
to  identification  and  classification  of  EDs  (Box  4.1).  There  is  wide  agreement  among  stakeholder 
groups that the lack of a harmonised approach is a problem. However, there are diverging stakeholder 
views on the way forward for how to accomplish a harmonised approach, for instance via the SVHC-
identification procedure under REACH, a dedicated hazard class under Classification, Labelling and 
Packaging  (CLP)  Regulation  and/or  the  UN  Globally  Harmonized  System  of  Classification  and 
Labelling of Chemicals (GHS) with or without categories, or via a separate legislation.  In a similar 
way, the implementation of a category of suspected endocrine disruptors would have the advantage of 
stimulating assessments and substitutions but could lead to the exclusion of substances that could be 
used safely. Another consideration is in the context of the PPPR and BPR, where the criteria for EDs 
do  not  include  a  suspected  category.  The  implementation  of  an  additional  hazard  class  in  the  CLP 
regulation and possibly categories could help to define clear regulatory triggers as part of assessment 
workflows from screening assessments to risk management measures. 

4.2.2 

Identification  through  Classification,  Labelling  and  Packaging  Regulation  hazard 
classes 

Currently  there  is  no  hazard  class  for  endocrine  disrupting  properties  under  the  Classification 
Labelling and Packaging (CLP) Regulation. Many known EDs are classified as carcinogenic or toxic 
to reproduction, or both. Along with mutagenic substances, these hazardous properties are considered 
to  produce  effects  of  a  serious  and  irreversible  nature  and  are  collectively  referred  to  as  CMRs 

https://echa.europa.eu/documents/10162/28327874/vanderlinden_bshd19_en.pdf/d2813dbe-a8db-f630-1dfe-
24d02c308fc5 

39 

 
 
                                                                                                                                                                     
(Carcinogenic,  Mutagenic  or  toxic  for  Reproduction).  The  CMR  categories  include  important  ED-
mediated  effects, such as cancers in hormone sensitive organs, and reproductive and developmental 
disorders, which might be ED-mediated. Six of the seven chemicals identified so far as Substances of 
very High Concern (SVHCs) for endocrine disrupting properties with respect to human health under 
REACH are also classified as reproductive toxicants (category 1A or 1B) under the CLP regulation. 

However,  the  substance  butyl  4-hydroxybenzoate  (butyl  paraben)  was  identified  as  ED  for  human 
health  in  REACH  in  June  2020,  but  is  not  classified  as  CMR,  since  effects  related  to  fertility  and 
development  has  not  led  to  a  harmonised  classification  as  toxic  for  reproduction.    In  addition, 
available toxicological data triggering CMR classification may not capture certain effects potentially 
mediated  by  endocrine  disruption,  such  as  certain  neurodevelopmental  and  metabolic  disorders.  As 
methods and data on thyroid disruption, steroidogenesis and other less studied modalities of endocrine 
disruption become available,  it is expected that more substances  will be identified  as EDs  based on 
effects  beyond  those  defining  CMRs.  Other  hazard  classes,  under  the  CLP  Regulation,  relevant  to 
human health, focus on specific target organ toxicity (STOT) and include potency considerations such 
that  a  substance  toxic  to  e.g.  the  thyroid  may  not  be  classified  if  the  effects  are  only  seen  above  a 
certain exposure concentration. Such substances would remain unclassified in relation to the adverse 
effect, but may still fulfil the definition of an ED. 

In  relation  to  wildlife,  CLP  classification  for  ecotoxicity  is  generic  and  does  not  refer  to  specific 
modes  of  toxic  action.  Many  known  EDs  happen  to  be  also  classified  using  the  aquatic  hazard 
classification scheme (chronic categories 1 to 4). However, data triggering this classification are the 
chronic  no  observed  effect  concentration  (NOEC)  if  available,  fish  bioconcentration  factor  (BCF) 
and/or degradable properties of the chemical. This means that if the chronic NOEC is based on a test 
which does not have specific endocrine-mediated endpoints (e.g. OECD TG 210), an ED may or may 
not be classified as a chronic aquatic toxicant. 

The importance of horizontal classification of EDs under the CLP Regulation is widely recognised22 
since  a  hazard  classification  may  be  used  to  trigger  risk  management  measures  in  many  so-called 
‘downstream’  product  and  sector-specific  regulations  and  directives.  For  example,  the  CLP  hazard 
classification of substances is also the basis for the identification and classification of hazardous waste 
containing them. 

CMRs  of  categories  1A  or  1B  can  be  identified  as  substances  of  very  high  concern  (SVHC)  under 
REACH  and also fulfil  the cut-off criteria for non-approval under the plant  protection products and 
biocidal  products  regulations  (unless  the  limited  derogation  possibilities  in  the  Regulations  apply). 
Identification  of  a  CMR  as  an  ED  for  human  health  will  probably  not  lead  to  any  additional  risk 
management  measures,  where  they  are  already  the  strictest  (see  4.4  Risk  Management)  but  may 
nevertheless  contribute  to  the  overall  evaluation  within  a  risk-benefit  context  and  facilitate 
assessments of combined exposure/mixtures. In addition, as  described above, not all EDs for human 
health  are  identified  as  CMRs  and  identification  as  an  ED  for  the  environment  may  also  trigger 
additional risk management measures. 

 22SWD(2019) 199 

40 

 
 
 
 
 
 
                                                      
Box  4.1:  Stakeholders’  answers  to  questions  related  to  the  lack  of  a  horizontal  approach  to 
identification and classification of EDs.*,**  

100%

90%

80%

70%

60%

50%

40%

30%

20%

10%

0%

important
problem

not a problem

yes

no

yes

no

yes

no

To what extent does the
absence of harmonised criteria
pose a problem to a coherent
approach for the identification
of EDs?

Do you think that the lack of a
hazard category covering
endocrine disrupting properties
in the CLP Regulation and/or
GHS poses a problem for the
coherent identification of EDs?

Do you think that the lack of a
hazard category covering
endocrine disrupting properties
in the CLP Regulation and/or
GHS poses a problem for the
coherent risk management of
EDs?

Do you think that a category of
suspected endocrine disruptor
should be introduced?

Other
Trade union
Public authority

Business association
Civil society organisations

Company/business organisation
Academic/research institution

From the targeted stakeholders survey, the majority of respondents from all stakeholder groups think 
that the absence of harmonised criteria poses a problem to a coherent approach for the identification 
of EDs. The main motivations reported are:  
a.  Potential for inconsistent identification between pieces of legislation/contradictory conclusions on 
the same chemical. For example, the adopted ED criteria under Biocidal Product Regulation (BPR) 
are applicable both to biocidal active substances and non-active substances, i.e. co-formulants. Co-
formulants are regulated under REACH, yet they may also be evaluated under the BPR against the 
ED criteria. Therefore, there is potential for inconsistencies between REACH and BPR regarding 
data evaluation, requirements and conclusions on co-formulants. 

b.  Creates regulatory uncertainty and ambiguity among all groups of stakeholders. 

41 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
c.  Potential  for  duplication  of  efforts  by  authorities/higher  costs  for  companies/unnecessary 

duplication of in vivo tests. 

d.  Gaps and incoherent level of protection from exposure of people and wildlife to EDs. For example, 

inconsistent identification and lack of control measures in occupational settings. 

e.  Difficulty in defining a hazard class and to develop OECD standardised methods accordingly. 

Respondents answered in a similar way to the two questions on whether the absence of an ED hazard 
class  in  Classification  Labelling  and  Packaging  (CLP)  Regulation  and/or  the  Globally  Harmonized 
System  of  Classification  and  Labelling  of  Chemicals  (GHS)  poses  a  problem  for  the  coherent 
identification and for the coherent risk management of EDs. Most public authorities and trade unions 
answered  “yes”;  most  companies/business  organisations  and  business  associations  answered  “no”, 
with more mixed responses from the other stakeholder groups 

Among those who answered “yes”, the main arguments were: 
a.  Only  a  hazard  class  ensures  a  consistent  approach  for  all  manufacturers/formulators/downstream 

users communicating and managing the risks associated with using EDs. 

b.  A hazard class would lead to coherent identification of EDs, as with Carcinogenic, Mutagenic and 
toxic  to  Reproduction  (CMR)  substances,  creating  a  common  basis  for  identification  and  risk 
management. 

c.  A hazard class would allow better labelling and better protection. 
d.  Lack of a hazard class hinders identification of EDs and appropriate management of materials and 

waste streams.  

e.  A GHS hazard class could lead to coherent identification of EDs worldwide. 

Among those who answered “no”, the main arguments were: 
a.   Endocrine activity is a mode of action, while GHS/CLP focus on adverse effects. Adverse effects 
triggered  by  endocrine  activity  are  already  covered  by  existing  GHS/CLP  hazard  classes.  ED 
classification would be redundant. 

b.  Classification  is  not  necessary  for  risk  management.  For  example,  REACH  already  allows  ED 

identification and management of associated risks. 

c.  International  agreement  on  a  new  hazard  class  under  GHS  will  take  years  and  may  delay 

identification of EDs. 

d.  There are other alternatives to CLP classification, such as a dedicated identification system. 

The  possibility  of  introducing  a  category  of  suspected  ED  is  favoured  by  most  respondents  from 
public authorities, civil society organisations and trade unions, but not favoured by most respondents 
from companies/business organisations and business associations.  

Respondents with a favourable opinion were asked what the consequences of a suspected ED category 
should be. They responded that the main regulatory consequences should be: 
a.  Application  of  a  similar  level  of  management  as  for  CMRs  (which  have  suspected  categories), 
resulting in ban/restriction of uses with possible derogations. 
b. Enabling authorities to prioritise chemicals for regulatory action. 
c.  Communication  of  information  to  the  supply  chain,  workers  and  consumers  by  e.g.  appropriate 

labelling.  

According to the same group of respondents, the introduction of a suspected ED category could: 
 a.  Decrease  the  exposure  to  EDs,  leading  to  better  protection  for  human  health,  particularly 
vulnerable groups, and the environment.   
b. Stimulate searches for substitutes with potential for innovation and economic development 
c. Stimulate further investigations of the suspected compounds. 

42 

 
 
 
 
 
 
 
 
d. Decrease health costs, increase protective measures for workers, increase costs for further testing 

and evaluations.  

The respondents against the introduction of a “suspected” endocrine disruptors category suggested  
a. A suspected category may cause unnecessary public concern.  
b.  Such  a  category  would  have  a  high  economic  impact,  by  stigmatising  compounds,  and  by  the 

additional complexity and bureaucracy that would be involved by such a category.  

*Answers are given in percentage of respondents from each stakeholder group. For more details see Annex 2. 
**Respondents  to  all  three  surveys  (citizens,  stakeholder  and  SME  surveys)  were  self-selected  and  thus  not 
necessarily representative of the full range of views of these groups. 

Some  of  the  stakeholders  who  disagree  with  the  introduction  of  a  hazard  class  covering  endocrine 
disrupting properties in the CLP Regulation and/or GHS state that it would be redundant as adverse 
effects  triggered  by  endocrine  activity  are  already  covered  by  existing  GHS/CLP  hazard  classes. 
However, this would be true only for some endocrine–related effects, excluding for example effects of 
obesogens, as tests generally used for classification in the existing hazard classes cannot identify such 
EDs. Regarding the statement that classification is not necessary for risk management, this may be the 
case.  However,  the  CLP  Regulation  may  have  advantages  with  respect  to  simplification  since  it  is 
often  the  instrument  currently  used  for  hazard  classification.  It  is  also  referred  to  by  many  of  the 
current  product  and  sector-specific  regulations  in  relation  to  invoking  specific  risk  management 
measures and thus an ED hazard class could be considered for use in a similar way. Communication is 
also  an  important  aspect  of  classification  through  the  CLP  Regulation  with  respect  to  protection  of 
workers and consumers (especially vulnerable groups) although this issue has been partially resolved 
for workers through the requirements to indicate endocrine disrupting properties on safety data sheets. 

There  is  a  commitment  of  the  EU  to  explore  the  possibility  to  harmonise  classification  at  the 
international  level  through  the  UN  GHS.  However,  it  could  take  many  years  to  reach  agreement  at 
international  level,  if  at  all,  and  thus  delay  action  at  EU  level  with  the  consequent  implications  on 
effectiveness. Alternatively, as also stated by some stakeholders, REACH could also be a potentially 
suitable  instrument  that  could  be  further  reinforced  to  ensure  consistent  ED  identification  and 
appropriate risk management measures across sectors and products.  

The views on the introduction of a suspected category of EDs are more polarised across the different 
stakeholder  groups.  Ideally,  testing  for  endocrine  disruption  should  proceed  until  a  decision  can  be 
made  that  the  substance  is  or  is  not  an  ED.  In  practice  it  may  be  difficult  to  generate  sufficiently 
conclusive evidence one way or the other for all substances to inform on regulatory decision making 
in a reasonable timeframe. Hence the suggestion for a ‘suspected’ category. Proponents of a suspected 
category  argue  that  it  would  be  prudent  to  flag  the  possible  hazardous  properties  of  the  substance, 
while the detractors consider that it would “stigmatise” a substance that may not have such properties 
and discourage users from its use. Important considerations in the discussion are deciding where on 
the spectrum of evidence the criteria for a ‘suspected ED’ should be set, and what risk management 
measures, if any, should be applied to such a category. In the context of setting the criteria for biocidal 
and  plant  protection  products  the  Commission  Communication23  stated  that  establishing  different 
categories  of  what  may  be  an  endocrine  disruptor  does  not  help  to  define  what  is  an  endocrine 
disruptor  and  would  decrease  legal  certainty  for  regulators  and  stakeholders  without  established 

23COM(2016) 350 

43 

 
 
 
 
                                                      
benefits in terms of protection of health and the environment. However, this approach with categories 
is, for example, already followed for CMRs. 

4.3

  Risk assessment 

4.3.1  Feasibility of risk assessment 

Risk assessment is the cornerstone of safety evaluation procedures across many pieces of chemicals 
legislation.  Risk  is  quantified  as  the  ratio  of  the  chemical  exposure  in  an  organism  or  in  an 
environmental media to an exposure level considered safe. The approach builds on the concept that, 
for a given substance, a biological threshold often exists for a given toxicological effect, below which 
exposure does not exert any adverse effect in organisms. Within a given regulatory framework, risk 
assessment  is  feasible,  when  such  a  threshold  can  be  derived  using  the  (eco)toxicological  data 
available.  

There  is  an  ongoing  debate  in  the  scientific  community  about  the  viability  of  performing  risk 
assessment for EDs. The debate is reflected in the views of members from the Endocrine Disrupters 
Expert Advisory Group (ED EAG), which was  composed of toxicologists and ecotoxicologists with 
regulatory and/or endocrinology backgrounds, nominated by Member State Competent Authorities for 
REACH,  the  Biocidal  Product  Regulation  (BPR),  and  the  Plant  Protection  Products  Regulation 
(PPPR),  relevant  industry  associations  and  non-governmental  consumer/environmental  protection 
organisations (Munn and Goumenou, 2013b). According to this report, most experts considered that 
biological thresholds of adversity are likely to exist; several maintained that it is difficult to estimate 
them based on currently available test methods, while others considered it is possible to estimate them 
with appropriate testing. There was lack of consensus on the sensitivity of existing methods to detect 
responses at low doses.   

The  debate  also  exists  in  the  context  of  EU  regulatory  assessments.  For  example,  in  2013,  in  its 
restriction  dossier  on  nonylphenol  ethoxylates,  the  Swedish  competent  authority  for  REACH  stated 
that “identifying safe concentration limits for all possible endpoints within the endocrine system that 
can be affected by EDs is not possible within the current test methods and would be inconsistent with 
the objective in REACH to reduce animal testing” (see Annex 5C, nonylphenol case study). The Risk 
Assessment Committee (RAC) abstained from any opinion about whether a threshold proposed during 
its discussions was sufficiently protective for all hazards of nonylphenol (NP), including those posed 
by endocrine disrupting properties, pointing to the then on-going discussion in the EU Commission on 
the possibility to derive a safe level of exposure24. Instead, it based its opinion on the identified risks 
for endpoints not related to endocrine disrupting properties. 

In the context of REACH authorisation, the Commission indicated in 2016 that EDs might or might 
not  have  a  threshold  and  that  “it  remains  the  responsibility  of  applicants  to  demonstrate  that  a 
threshold exists and to determine that threshold. Even though this might be particularly difficult for 
EDs, it cannot be excluded on the basis of current knowledge that it will be possible. It is up to RAC 
to assess the validity of the assessment and ultimately decide on the possible existence or not of this 
threshold”25. In the authorisation procedure, the application of risk assessment to demonstrate safety 
has been termed the ‘adequate control route’. However, adequate control based on risk assessment is 
not  an  option  if  a  threshold  cannot  be  demonstrated.  For  example,  NP  ethoxylates  (NPnEO)  were 
added  to  the  Authorisation  list  (Annex  XIV)  for  their  endocrine  disrupting  properties  for  the 

24RAC and SEAC (2014): Opinion on an Annex XV dossier proposing restrictions on NP and NPnEO 
25COM (2016) 814 

44 

 
 
                                                      
environment  (Annex  5C,  nonylphenol  case  study).  In  a  note  intended  to  provide  general  advice  to 
companies  intending  to  apply  for  authorisation  of  uses  of  octylphenol  and nonylphenol  ethoxylates, 
the RAC “did not consider that exposure values below [a conventionally derived] predicted no effect 
concentration were consistent with a ‘safe level’, specifically noting the uncertainties associated with 
the  endocrine  disrupting  properties  of  NPnEO”  (ECHA  RAC  2017).  To  date  no  applicant  tried  to 
demonstrate a safe threshold and applied for the adequate control route. In this case authorisations are 
granted  based  on  risk-benefit  considerations,  provided  that  exposure  is  minimised  and  alternative 
substances are not available. REACH restrictions require evidence of an unacceptable risk to human 
health  or  the  environment,  arising  from  the  manufacture,  use  or  placing  on  the  market  of  the 
substance.  In  cases  where  it  is  difficult  to  derive  safe  thresholds,  a  qualitative  assessment  of  the 
likelihood that effects are avoided can be used when implementing measures. In recent restrictions on 
chemicals  with  endocrine  disrupting  properties  (e.g.  DEHP,  nonylphenol  ethoxylates), 
the 
unacceptable  risk  was  proven  since  risk  ratios  exceeded  the  value  of  1.  In  both  cases,  the  endpoint 
assessed was not explicitly related to endocrine properties. 

In its 2013 opinion, EFSA’s Scientific Committee considered that biological thresholds of adversity 
do  exist  and  considered  human  and  environmental  risk  assessment  (taking  into  account  hazard  and 
exposure data/predictions) the best approach to inform risk management decisions in regulations that 
base  decisions  on  the  risk  and  level  of  concern  (EFSA  Scientific  Committee,  2013).  According  to 
EFSA’s Scientific Committee “EDs can therefore be treated like most other substances of concern for 
human  health  and  the  environment,  i.e.  be  subject  to  risk  assessment  and  not  only  to  hazard 
assessment”.  Risk  assessment  had  been  applied  to  assess  the  risk  of  bisphenol  A  (EFSA  Panel  on 
Food Contact Materials, Enzymes, Flavourings and Processing Aids, 2015) and phthalates (based on 
reprotoxic effects) in food contact materials (Annex 5B, DEHP cases study) before their identification 
as EDs under REACH. In these cases, the assessment factors applied to derive tolerable daily intakes 
can account for uncertainties related to endocrine-mediated effects. In the 2015 EFSA risk assessment 
of  BPA,  for  example,  uncertainty  in  mammary  gland,  reproductive,  neurobehavioural,  immune  and 
metabolic system effects justified an additional assessment factor of 6. 

The  Scientific  Committee  on  Consumer  Safety  (SCCS)  endorsed  the  2013  EFSA  opinion  on  EDs 
(SCCS  2014,  and  COM  (2018)  739)  and  evaluates  cosmetic  ingredients  based  on  risk  assessment, 
including  the  derivation  of  safe  exposure  thresholds.  To  date  the  SCCS  has  not  completed  an 
evaluation  for  substances  after  these  have  been  identified  as  EDs  under  other  legislation.  However, 
the  SCCS  is  currently  evaluating  five  substances  with  potential  endocrine  disrupting  properties 
(homosalate, octocrylene, benzophenone-3, resorcinol and propylparaben).  

Rather than being a means of demonstrating safety, risk assessment is also applied in some sectors to 
assess the probability of harm and conclude on tolerable risk levels for risk-benefit evaluations or risk 
mitigation. This is also the case for biocidal products, medical devices (human health risks as part of 
the  benefit-risk  analysis),  pharmaceuticals  (for  environmental  risks),  veterinary  medicines  (for 
environmental risks as part of the benefit-risk analysis).  

4.3.2  Differences in risk assessment 

The subdivision of assessment activities across policy areas means that the same chemical (or group 
of chemicals) might need to be assessed for human health or environmental endpoints under multiple 
frameworks  (Figure  3.1).  Although  agencies  and  Scientific  Committees  have  increasingly  sought 

45 

 
 
alignment  in  recent  years,  stakeholders  expressed  the  need  for  better  coordination  of  agencies  and 
committees26.  

The  three  case  studies  performed  for  this  Fitness  Check  (Annex  5)  were  chosen  to  evaluate  the 
horizontal  coherence  of  regulatory  assessments  for  EDs  across  policy  areas.  Differences  in  risk 
assessments  may  emerge  at  different  levels  –  chemical  grouping,  exposure  pathways  assessed, 
methodology  or data  used.  Where  EDs  have  been  assessed,  our analysis  did not  identify  significant 
deviations  from  the  standard  methodology,  described  in  the  guidance  documents,  owing  to  ED-
specific  considerations.  In  one  case,  when  conducting  the  risk  assessment  for  nonylphenol  in  the 
REACH restriction report, the Swedish competent authority introduced an extra assessment factor of 
10 in  the calculation of safe environmental concentrations to account for the incomplete knowledge 
and  the  uncertainties  related  to  its  ED  properties.  The  ECHA  Risk  Assessment  Committee  (RAC) 
opinion  did  not  endorse  the  approach  but  referred  to  the  risk  ratios  obtained  with  the  standard 
approach,  which  already  indicated  a  risk  (Annex  5C,  nonylphenol  case  study).  The  uncertainties 
associated  with  the  possible  peculiarities  of  endocrine  disrupting  effects  (i.e.  non-threshold,  non-
monotonic behaviour) are recognised and in some cases have been taken into account through the use 
of uncertainty factors, defined on a case by case basis. 

Differences  in  risk  assessments  performed  for  the  same  substance(s)  under  different  pieces  of 
legislation reflect differences in the legislative scope (especially, in the cases identified, the scope of 
the  exposure  assessment  and  the  chemical  grouping).  The  case  of  low  molecular  weight  phthalates 
recently assessed by ECHA and EFSA illustrates the challenge (Annex 5B, DEHP case study). Both 
agencies performed  a risk  assessment based on the same hazard (reproductive toxicity) and toxicity 
data.  The  two  assessments  differed  in  terms  of  the  definition  of  chemical  grouping  (DIBP  was  not 
assessed by EFSA since it is not authorised as an additive in FCM) as well as the approach and data 
used  to  estimate  exposure  (e.g.  exposure  sources  considered,  population  age  grouping,  food  intake 
estimates).  ECHA  concluded  that  there  is  risk  to  human  health  from  combined  exposure  and 
especially  of  significant  exposure  to  DEHP  from  the  diet  based  on  modelling  estimates.  EFSA’s 
assessment concluded that dietary exposure did not result in group-based or individual tolerable daily 
intakes  being  exceeded.  A  risk  is  obviously  more  likely  to  be  found  if  aggregate  exposure  from  all 
possible  sources  is  considered  rather  than  only  a  single  source.  The  two  assessments  are  consistent 
within  their  respective  mandates,  but  the  different  scopes  and  approaches  to  estimate  exposure 
resulted  in  different  regulatory  interventions,  reflecting  the  absence  of  a  coherent  cross-sector 
approach.  

The case study on nonylphenol revealed an example where hazard datasets are not harmonised across 
chemical  and  water  legislation,  leading  to  differences  in  derived  threshold  values  (Annex  5C, 
nonylphenol case study).  

Evidence from the case studies suggests that where the same substance(s) have been assessed under 
different  frameworks  it  is  difficult  to  ensure  coherence  of  assessments.  The  problem  is  generic  and 
does  not  relate  specifically  to  EDs.  Regarding  the  exposure  assessments,  when  differences  in  the 
exposure  scenario(s)  and  exposure  routes  assessed  are  linked  with  the  specific  scope  of  sectorial 
legislation,  the  issue  cannot  be  easily  solved  in  the  current  framework.  While  most  stakeholders 
largely agree on working towards a framework when one substance is associated with one assessment, 
based  on  a  shared  data  set  across  all  regulatory  sectors,  the  current  framework  does  not  provide  a 
systematic approach to integrate total aggregate exposure with sector-specific exposure scenarios. The 

26SWD(2019) 199 

46 

 
 
                                                      
Commission’s ambition to develop a one substance-one assessment approach may provide a means to 
address this issue. 

4.3.3  Consideration of vulnerable groups 

(Sub)population  groups  may  be  at  higher  risk  due  to  numerous  factors,  including  those  affecting 
external  exposure,  internal  exposure  and  biological  susceptibility  (Table  4.1).  Factors  affecting 
external and internal exposure are relevant in general but are not specific to EDs.  

Table 4.1. Factors contributing to higher risk of (sub)population groups and possible options to address 
them in risk assessment 

Factors contributing to higher risk 

Factors affecting 
(external) exposure 
dose 

Behaviours: crawling, mouthing, 
chewing 
Diet habits: higher intake of 
specific food categories such as 
baby food, food contact materials 
Exposure to specific 
environments: working place, 
outdoor lifestyle, indoor 
environments 
Ability to avoid exposure: 
intellectual and physical 
conditions  

(Sub)populations 
groups at higher risk 

Babies, toddlers 

Babies, toddlers, 
children 

Workers, children 

Possible options in risk 
assessment 
Tailored exposure 
scenarios 
Tailored exposure 
scenarios 

Tailored exposure 
scenarios 

Babies, toddlers, 
disabled, elderly 

Tailored exposure 
scenarios 

Factors affecting 
internal exposure 

Surface area to body weight 

Underdeveloped/ slow metabolism 
and elimination rates 
Underdeveloped blood-brain 
barrier/ placental transfer 

Factors affecting 
biological 
susceptibility 

Sensitive development stage/ 
immature organs 

Poor nutrition/health conditions 

Babies and young 
people 
Foetus, elderly 

Foetus 

Foetus, new-borns, 
adolescents, pregnant 
woman 
Ill people, elderly, low 
income population 

Correction factors, use of 
biomonitoring 
Correction factors, use of 
biomonitoring 
Sensitive test 
methods/long term 
epidemiological studies 
Sensitive test 
methods/long term 
epidemiological studies 
Assessment factors for 
population variability 

Several  pieces  of  legislation  within  the  scope  of  this  Fitness  Check  consider  risks  to  vulnerable 
groups. Where such risks are taken into consideration, the definition of vulnerable population varies 
as there is no horizontally applicable definition of 'vulnerable group'. The Plant Protection Products 
Regulation and the Biocidal Products Regulation specifically define vulnerable groups in relation to 
chemical  risks:  both  refer  to  ‘pregnant  and  nursing  women,  the  unborn,  infants  and  children,  the 
elderly and workers and residents subject to high exposure to active ingredients over long term’. The 
rationale for explicitly mentioning specific vulnerable groups in legal provisions is not always clear27. 
For example, legislation on detergents and food contact materials does not include specific provisions, 
but  cosmetic  products  and  other  food  legislation  (e.g.  food  additives)  does.  However,  lack  of 
reference  or  definition  of  vulnerable  groups  in  legislation  does  not  necessarily  lead  to  lack  of 
assessment or action, as exemplified by the risk assessment of and restrictions on substances in food 
contact materials. 

27SWD(2019) 199 

47 

 
 
 
 
                                                      
Current  risk  assessment  methodologies  across  chemical  safety  legislation  aim  to  cover  risks  to  the 
general population including the most sensitive sub-populations (i.e. vulnerable groups). In practice, 
the default safety/assessment factors applied when extrapolating from the animal data to humans may 
not be considered large enough and additional assessment factors are sometimes used to cover these 
vulnerable  groups.  Thus,  risks  to  vulnerable  groups  are  addressed  on  a  case-by-case  basis  through 
triggers  and  guidance  established  under  sector-specific  legislation.  Assessments  for  specific 
vulnerable  groups  are  mostly  triggered  by  factors  affecting  internal  and  external  exposure  and 
focussed  mainly  on  neonates  and  young  children.  Some  examples  of  how  vulnerable  groups  are 
considered in regulatory assessments are reported in Box 4.2. 

Under REACH, guidance exists to account for specific exposure situations and to derive specific no-
effect  levels  (DNELs)  for  vulnerable  groups  (non-ED  specific)  with  an  emphasis  on  reproductive 
toxicity28.  The  REACH  guidance  on  exposure  refers  to  the  OECD  considerations  when  assessing 
children’s exposure to chemicals and a decision tree for deciding when to trigger tailored assessments 
for children (OECD, 2019). In this context, children are broadly defined as any human from birth to 
21 years old, according to the WHO definition.  

The Cosmetic Products Regulation requires  a specific assessment for products intended for children 
under  3  years.  The  Scientific  Committee  on  Consumer  Safety  (SCCS)  Notes  of  Guidance  mention 
certain circumstances, which might require specific margins of safety for certain subpopulations, such 
as childrenError! Bookmark not defined.. Correction factors are reported for different age groups to 
account for higher surface area per body weight. Other factors listed that can affect vulnerability of 
new-borns are toxicokinetic parameters (slower metabolism and elimination rates), and sensitivity to 
inflammation for specific uses (i.e. for products intended for use in the nappy area).  

Considerations about the level of protection of vulnerable groups to EDs are presented in  Section 5, 
including responses from stakeholders and citizens surveys (Box 5.9). 

Box 4.2 Examples of how vulnerable groups are considered in regulatory assessments  

  DEHP  and  other  low  molecular  weight  phthalates  under  REACH  and  Food  Contact  materials 
Regulation (Annex 5B, DEHP case study). The 2017 RAC assessment acknowledged that Derived 
No  Effect  Levels  (DNELs)  derived  for  reproductive  toxicity  from  developmental  studies  are 
relevant  to  pregnant  women  and  the  foetus  but  less  so  to  children.  Nonetheless,  DNELs  were 
deemed conservative and therefore acceptable to evaluate risks for children. The EFSA approach 
to DNEL derivation for phthalates was consistent with ECHA’s. However, the subpopulations (age 
ranges) considered in the exposure assessment of low molecular weight phthalates by ECHA and 
EFSA reflected differences in available datasets.  

  3-BC under the Cosmetic Products Regulation. The SCCS found that 3-BC was not safe for human 
health  and  did  not  consider  it  necessary  to  tailor  the  assessment  to  specific  vulnerable  groups 
(Annex 5A, 3-BC case study). In the general case, an assessment factor of 10, accounting for intra 
species  (between  human)  variability  of  toxicokinetic  and  toxicodynamic  parameters,  is  factored 
into the overall default margin of safety required of 100.  

  Propyl-  and  butylparabens  under  the  Cosmetic  Products  Regulation.  In  its  assessment  the  SCCS 
took into consideration additional risk factors for children below the age of 6 months. Although the 

28REACH guidance on information requirements and chemical safety report: chapters R.15.2.5, Appendix 
R.15.6 and chapter R.8 

48 

 
 
 
 
                                                      
dermal absorption in new-borns is similar to that in adult skin, in the light of both the immature 
metabolism and the possibly damaged skin in the nappy area, the SCCS could not rule out a risk, 
based  on  worst  case  scenarios  of  aggregate  exposure  and  higher  but  unquantified  dermal 
absorption. A realistic quantitative risk assessment for children was not possible as information on 
internal exposure was not available.  

4.3.4  Prioritisation and Environmental Quality Standards under the water legislation 

The  regulation  of  EDs  under  water-related  legislation  is  largely  dependent  on  data  generation  and 
evaluation carried out under other regulatory frameworks, such as REACH, or in scientific studies. In 
recent  years,  substance  prioritisation  and  setting  of  Environmental  Quality  Standards  (EQS)  have 
taken  advantage  of  the  increased  amount  of  ecotoxicological  information,  including  information  on 
ED-mediated  effects,  which  has  become  available  through  chemical  registration  dossiers  under 
REACH, the Plant Protection Products Regulation and the Biocidal Products Regulation29.  

The  Water  Framework  Directive  (WFD)  applies  a  combination  of  generic  and  specific  risk 
considerations  from  both  experimental  and  modelling  data  for  the  classification  of  chemicals  as 
priority  substances  (PS)  and  priority  hazardous  substances  (PHS).  The  first  list  of  PS  followed  a 
scoring-based  ranking  approach, 
including  elements  of  exposure  and  effects  as  well  as 
biodegradability  and  bioaccumulation  potential30.  Nonylphenol  and  DEHP,  for  example,  were 
recommended for inclusion in the list for their relatively high modelling-based ranking combined with 
additional  evidence  of  environmental  occurrence  and  endocrine  disrupting  effects  (Fraunhofer-
Institut, 1999).  

The designation of PS or PHS considers both generic (e.g. for Persistent, Bioaccumulative and Toxic, 
PBT  substances)  and  specific  risk  criteria31.  For  the  final  designation,  "additional  considerations", 
including  suspected  endocrine  disrupting  potential,  can  influence  the  designation.  For  nonylphenol, 
evidence  of  “widespread  risk  to  or  via  the  aquatic  environment”  32  assessed  under  pre-REACH 
regulation  793/93  determined  the  classification33.  DEHP  was  not  originally  designated  as  a  priority 
hazardous substance, but it was designated as such in 2013.  

Prioritisation approaches have evolved over the years, but have maintained a combination of generic 
(PBT,  Substances  of  Very  High  Concern  (SVHC),  and  Persistent  Organic  Pollutant  (POP)  criteria) 
and specific risk approaches from experimental and modelling data. An early step of the prioritisation 
carried out in 2011 comprised scoring against four criteria: persistence, bioaccumulation, toxicity and 
endocrine disrupting properties29.   

Environmental Quality Standards are established for both PS and PHS, even though the WFD aims to 
ensure the phase-out of PHS emissions to water, not only a reduction in those emissions as in the case 
of the other PS. The logic of setting EQS for PHS has been questioned by some stakeholders, but it is 
generally  accepted  that  there  is  a  need  for  a  benchmark  in  the  context  of  chemical  water  quality 
assessments. The persistent nature of many PHS makes it difficult to comply with the EQS, let alone a 
more  ambitious  target.  EDs  are  treated  like  other  chemicals  when  deriving  EQS  (e.g.  Annex  5C, 

29SEC(2011) 1544 
30Working Document ENV/191000/01 
31Checks 1 to 6 of Working Document: https://ec.europa.eu/environment/water/water-
dangersub/pdf/wd_env_191000_01_final.pdf  
32ECB 4/15/00 
33COM/2001/17 

49 

 
 
 
                                                      
nonylphenol  case  study).  However,  if  there  are  indications  of  adverse  effects  via  endocrine  activity 
(e.g.  in  vivo  bioassays)  an  additional  assessment  factor  may  be  considered  to  cover  the  anticipated 
effects34.  

Recently, the Drinking Water Directive (DWD) has stepped up efforts to monitor risks from exposure 
to  EDs.  Under  the  Drinking  Water  Directive,  three  substances  have  been  proposed  as  indicators  of 
estrogenic  contamination  from  sewage  effluents,  based  on  WHO  recommendations:  β-oestradiol, 
bisphenol  A  and  nonylphenol35.  Bisphenol  A  was  added  to  Annex  I  with  a  health-based  parametric 
value  based  on  a  2015  EFSA  opinion  (EFSA  Panel  on  Food  Contact  Materials  et  al.,  2015),  and 
nonylphenol and β-oestradiol will be added to a watchlist, for assessing their occurrence and treatment 
efficacy where necessary.  

4.4

  Risk management 

4.4.1  Management approaches across legislation on chemicals  

Generally,  regulatory  intervention  on  chemicals  can  be  based  directly  on  their  hazardous  properties 
(generic risk approach), on the result of risk assessments (specific risk approach), or on risk-benefit 
considerations36. Legislation often combines elements of the different approaches. For example, under 
REACH  the  listing  as  Substance  of  Very  High  Concern  (SVHC)  is  hazard-based  (generic  risk 
approach);  application  for  authorisations  may  be  based  on  (adequately  controlled)  risk  or  on  risk-
benefit arguments; restrictions require that there is evidence of an unacceptable risk to human health 
or the environment. Restriction specifications are also substantiated by (socioeconomic) risk-benefit 
considerations.  Product-level  legislative  instruments,  such  as  the  Cosmetic  Products  Regulation 
(CPR),  Toy  Safety  Directive  and  the  Food  Contact  Materials  (FCM)  Regulation  apply  generic  risk 
approaches  for  Carcinogenic,  Mutagenic  and  toxic  to  Reproduction  (CMR)  hazard  classes,  with 
specific risk approaches for the risk management of other types of hazardous substances. Exceptions 
exist where the specific risk approach can also be applied to CMRs. While based on assessments by 
EU  Agencies  and  scientific  committees,  decisions  can  also  be  subjected  to  the  application  of  the 
precautionary principle.  

The Fitness Check on chemical legislation (excluding REACH) concluded: “In many instances, these 
differences reflect variations in legal scopes and objectives and thus different needs in terms of depth 
of  analysis  and  evidence  required  to  draw  conclusions  and  decide  upon  any  risk  management 
measures that may be needed. Therefore, these differences do not necessarily imply incoherence. They 
illustrate  the  legislator’s  intention  to  provide  a  framework  that  is  tailored  to  the  specific 
circumstances  of  the  substances  used  and/or  the  likely  hazards  and  exposure”;  and  further  on  risk 
management  of  known  adverse  effects:  “The  majority  of  currently  known  adverse  effects  on  human 
health  and  the  environment  are  covered  [in  legislation]”.  However,  “some  inconsistencies  occur 

34https://rvs.rivm.nl/sites/default/files/2019-04/Guidance%20No%2027%20-
%20Deriving%20Environmental%20Quality%20Standards%20-%20version%202018.pdf 
35Drinking Water Parameter Cooperation Project of the WHO Regional Office for Europe "Support to the 
revision of Annex I Council Directive 98/83/EC on the quality of water intended for human consumption 
(Drinking Water Directive) Recommendation", 11 September 2017 
36In the context of this fitness check “specific risk” approaches imply the use of safe (or acceptable) thresholds 
to determine whether or not there is a risk. “Risk-benefit” approaches do not always require that a risk is 
quantified. 

50 

 
 
 
                                                      
regarding risk management decisions for EDs […]”37. This analysis did not go in depth, referring to 
the decision by the Commission to launch the present Fitness Check on EDs. 

Substances  with  endocrine  disrupting  properties  pose  specific  challenges  for  their  assessment.  The 
identification of EDs demands a significant amount of information to clarify potential modes of action 
and  different  effects,  which  often  necessitates  additional  testing  (possibly  including  further  animal 
testing).  Risk  assessment  approaches  have  limitations  for  ED-mediated  effects  in  those  cases  for 
which  it  is  difficult  to  derive  a  safe  (or  acceptable)  threshold  based  on  the  available  scientific 
evidence.  The  same  limitations  add  to  the  uncertainty  of  risk-benefit  analysis.  However, 
socioeconomic considerations based on other approaches can be applied for non-threshold substances. 
The  legislator  has  opted  for  different  approaches  to  risk  management,  considering  policy-specific 
objectives and constraints (See Table 3.1 and Annex 4 for a complete description). Under the Plant 
Protection  Products  Regulation  (PPPR)  and  the  Biocidal  Products  Regulation  (BPR)  the  legislator 
chose to ban EDs but put in place specific derogation possibilities. The approach implemented under 
REACH  is  also  a  generic  risk  approach  insofar  as  EDs  can  be  identified  and  listed  as  SVHCs.  The 
intended consequence of listing SVHC in Annex XIV of REACH is substitution as soon as technically 
and  economically  feasible.  Authorisation  may  be  granted  if  risks  are  adequately  controlled  or  if 
benefits outweigh risks (e.g. authorisations of DEHP and nonylphenol ethoxylates). Restrictions under 
REACH  follow  a  specific  risk  approach  and  take  socioeconomic  considerations  into  account. 
Regulations  on  medical  devices  and  in  vitro  diagnostic  medical  devices  require  a  risk-benefit 
justification  for  EDs  (identified  via  REACH  and,  only  for  medical  devices,  via  the  BPR).  Thus,  in 
PPPR, BPR, and the medical devices regulation, the management approach for EDs is comparable to 
that  applied  to  CMRs.  In  the  case  of  REACH,  however,  the  automatic  ban  applied  to  CMRs  in 
mixtures for consumer use is not applicable to EDs.  

Where legislation does not make specific reference to EDs (e.g. Cosmetic Products Regulation, Food 
Contact  Materials  Regulation)  the  specific  risk  approach  is  applied.  Also  the  Toy  Safety  Directive 
does  not  refer  to  EDs  but  this  is  a  particular  case  because  risk  management  overlaps  with  REACH 
with regard to human health concerns. Classification as hazardous chemicals (including carcinogens 
and  mutagens)  is  the  main  trigger  to  risk  management  provisions  under  Occupational  Safety  and 
Health (OSH) legislation through a hierarchy of measures from preventing exposure to reducing it to 
the lowest level technically possible, and in waste legislation through the classification of hazardous 
waste.   

The legislator opted for different risk management approaches based on specific policy objectives and 
considerations, including: 

- Application of the precautionary principle.  When there are reasonable grounds for concern that 
potential hazards may affect the environment or human, animal or plant health, or when the available 
data  do  not  allow  to  conclude  on  the  absence  of  risk  following  a  detailed  risk  evaluation,  the 
precautionary  principle  has  been  politically  accepted  as  a  risk  management  strategy.  The  approach 
under  both  the  PPPR  and  the  BPR  is  “underpinned  by  the  precautionary  principle”  taking  into 
account the specific nature of the products in question and the scientific uncertainties regarding their 
assessment  (for  example  as  regards  the  existence  of  a  safe  limit  of  exposure)38.  In  other  cases,  the 
precautionary principle is invoked for substance-specific decisions. For instance, it served as a basis 
for  the  currently  applicable  ban  of  Bisphenol  A  (BPA)  in  baby  bottles  since  2011  (Commission 

37SWD(2019) 199, part 1 
38COM(2018) 734 

51 

 
 
                                                      
Implementing  Regulation  (EU)  321/2011)  and  more  recently  for  FCM  aimed  at  infants  and  young 
children (Regulation (EU) 2018/213). 

-  Risk-benefit  analysis.  In  combination  with  an  evaluation  of  available  alternatives,  risk-benefit 
analysis  is  the  principle  of  approval  procedures  for  medical  devices  (e.g.  DEHP).  It  is  also  applied 
under REACH for authorisations (e.g. socioeconomic route in REACH authorisations of nonylphenol 
ethoxylates)  and  restrictions,  and  under  the  Biocidal  Products  Regulation  for  derogations  to  the 
general  non  approval  of  active  substances  identified  as  EDs.  For  human  medicines,  therapeutic 
benefits  have  the  priority.  Unintended  effects  on  the  environment  need  to  be  assessed  and  to  some 
extent managed (e.g. through waste management) but do not impact approval procedures. 

- Trade-offs between policy objectives. Differences in the objectives between chemical, product and 
waste  regulation  (e.g.  safety  vs  recyclability  targets)  unavoidably  result  in  trade-offs.  For  example, 
decisions on authorisation for certain SVHCs in secondary materials is influenced by consideration of 
the benefits of recycling (Annex 5B, DEHP case study). 

While  policy-specific  objectives  and  considerations,  such  as  the  ones  highlighted  above,  generally 
explain  the  rationale  behind  the  current  differences  in  risk  management  approaches,  the  rationale  is 
not always clear and explicit. For example, the co-legislator’s choice for plant protection products and 
biocidal products was justified by “the specific nature of the products”38, which can be interpreted as 
the likelihood of exposure and toxicity. This argument is not clear or always supported by scientific 
evidence of higher ED-related risks compared to other sectors. Another more specific example is the 
different derogation principles under the Plant Protection Products Regulation (negligible exposure or 
essential  use)  and  the  Biocidal  Products  Regulation  (negligible  risk,  essential  use,  or  risk-benefit 
considerations).  Stakeholders  often  criticise  situations  where  substances  are  restricted  under  some 
regulations but not under others and consider them not justified (Box 4.3). 

Even where regulations apply the same risk management approach, differences in the scope of a risk 
assessment  can  also  result  in  different  risk  management  measures  for  the  same  substance(s).  While 
not  ED-specific,  this  issue  poses  a  challenge  to  the  coherence  of  interventions  across  sectors,  as 
described in Chapter 4.3.2 and Annex 5B (DEHP case study).  

Overall, it can be concluded that different approaches to risk management have arisen as solutions to 
specific  policy  considerations.  Although  based  on  a  limited  number  of  examples  (Table  1.1),  this 
Fitness Check found no cases of inconsistent risk management caused by ED specific issues, such as 
the lack of a horizontal approach to identification.  

However, the difficulty in choosing a risk management approach is partly related to the fundamental 
scientific  question  of  whether  EDs  are  (all)  threshold  or  non-threshold  substances.  There  is  no 
scientific  consensus  on  the  threshold  question.  In  fact,  since  EDs  cover a  multitude  of  modes  of 
action, in some cases it may be justified to assume that a threshold exists and to follow a specific risk 
approach. In the absence of scientific consensus, legislation can either opt for an approach that does 
not require an answer to the question (e.g. generic risk approach with (limited) derogations as used for 
plant protection products and biocidal products) or it can determine case by case whether or not a safe 
(or acceptable) threshold can be quantified and consequently apply an appropriate risk management 
approach,  as  done  in  REACH,  where  a  risk/impact-benefit  approach  applies  if  it  is  not  possible  to 
determine  a  threshold39.  Certain  pieces  of  sectorial  legislation  (e.g.  Cosmetic  Products  Regulation, 
Food Contact Materials Regulation) not only lack specific provisions for assessing EDs but also lack 
specific  guidance  on  how  to  deal  with  EDs  for  which  it  is  not  possible  to  quantify  a  safe  (or 

39COM(2016) 814 final 

52 

 
 
                                                      
acceptable)  threshold.    In  practice,  in  cases  where  a  threshold  cannot  be  established  the  regulatory 
approach  followed  under  EU  legislation  is  to  minimise  exposure  as  far  as  possible,  including  the 
option to prohibit the use of a substance. Options for consolidation compatible with the Commission’s 
ambition  of  “one  substance  one  assessment”  should  be  explored,  with  the  specific  aim  to  minimise 
exposure  to  EDs.  If  the  current  situation  persists,  many  stakeholders  will  continue  criticising  the 
status quo for its lack of coherence, effectiveness and efficiency (Box 4.3). 

4.4.2  Management of EDs through water legislation 

Chemicals  listed  as  Priority  Substances  (PS)  under  the  Water  Framework  Directive  (WFD)  require 
EU-wide  monitoring  as  well  as  measures  to  achieve  the  progressive  reduction  in  the  emissions  of 
Priority  Substances,  the  cessation  of  emissions  of  Priority  Hazardous  Substances  (PHS)  in  a 
reasonable time frame, and compliance with the Environmental Quality Standards (EQS). Provisions 
in  the  water  sector,  however,  are  mostly  limited  to  end-of-pipe  interventions,  such  as  increasing 
wastewater treatment standards. The identification per se of a substance as a priority substance under 
the  WFD  does  not  necessarily  trigger  any  risk  management  process  beyond  the  WFD,  although 
several pieces of legislation require consideration of the need to meet the EQS set for them. Similarly, 
the  identification  of  EDs  through  chemical  legislation  does  not  automatically  have  regulatory 
consequences  under  the  WFD  (see  4.3.4).  For  PS  and  PHS  substances  that  are  authorised  under 
upstream  legislation  on  chemicals  for  uses  leading  to  environmental  emissions,  it  is  problematic  to 
minimise  or  eliminate  emissions  to  the  aquatic  environment.  This  is  a  challenge  for  PS  in  general, 
including  EDs  such  as  nonylphenol  (Annex  5C,  nonylphenol  case  study)  and  was  mentioned  by 
several  stakeholders  (see  Annex  2).  The  issue  reflects  a  generic  lack  of  coordination  between  the 
WFD and risk management measures taken under other upstream legislation on chemicals, as pointed 
out  by  the  recent  fitness  check  of  EU  water  legislation40,  despite  recent  efforts  to  require  better 
coordination41. For example, there is no link to the objectives of the WFD in legislation on human and 
veterinary pharmaceuticals. 

Regulatory efforts to manage chemicals of concern including EDs have been stepped up recently also 
in other pieces of water legislation. The coherence of the Drinking Water Directive (DWD) with the 
WFD  is  especially  important  as  the  protection  of  drinking  water  resources  is  established  as  an 
indispensable  part  of  the  plans  and  measures  under  the  WFD.  The  proposal  for  a  new  DWD  to  be 
adopted  by  the  end  of  2020  implements  a  specific  risk  approach,  requiring  further  prevention  and 
mitigation measures to protect drinking water sources. It requires a risk assessment of the catchment 
area(s) to be carried out aimed at reducing the level of treatment required for the production of water 
intended for human consumption, for instance by reducing the pressures causing the pollution of the 
water bodies. MS are asked to pay particular attention in their risk assessment to endocrine disrupting 
substances, and should, where necessary, require water suppliers to also monitor those substances and 
other parameters included in the DWD watch list if considered a potential risk to human health, and to 
treat the water accordingly.  

Box 4.3: Inconsistencies, gaps or overlaps in the way endocrine disruptors are regulated in the 
EU:  summary  of  the  views  of  stakeholders  taken  from  the  surveys  conducted  as  part  of  this 
fitness check (Annex 2)* 

40SWD (2019) 439 
41Article 7a of the EQSD 

53 

 
 
 
 
                                                      
 

Inconsistencies  exist  in  how  EDs  are  identified  (e.g.  lack  of  horizontal  criteria  for  EDs  and/or 
suspected  EDs  under  Classification,  Labelling  and  Packaging  (CLP)  Regulation)  and  regulated 
across different EU legislative frameworks; e.g. whereas EDs are regulated based on hazard-based 
cut-offs (with very limited derogation possibilities) in the context of pesticides and biocides, other 
frameworks  such  as  cosmetic  products,  toys  and  medical  devices  (may)  regulate  endocrine 
disruptors  based  on  case-by-case  risk  assessment.  These  inconsistencies  may  lead  to  different 
conclusions  on  restrictions  across  regulations  (if  indeed  the  same  substances  are  present  in  all 
these products), which may be difficult to communicate to the citizens. 

  There are inconsistencies with regard to restrictions across sectors for several substances that are 
still present in consumer goods: DEHP has been identified as a human endocrine disruptor under 
REACH  and  it  is  still  allowed  at  high  concentrations  in  plastic  medical  devices;  low  molecular 
weight  phthalates  such  as  DEHP  are  authorized  for  use  in  food  contact  materials  (FCMs)  with 
restrictions of use and on migration into food; while REACH restricted their use in most of the 
consumer products; bisphenol A has been banned from FCM  specifically for infants and young 
children  including  feeding  bottles  but  it  is  still  used  in  other  products  or  packaging  containing 
foods  that  are  also  fed  to  infants  and  young  children;  triclosan  cannot  be  used  in  food  contact 
materials and is not approved as a biocide but it is allowed in personal care products; butylated 
hydroxytoluene  (BHT)  is  allowed  in  certain  foods  and  in  food  packaging,  while  it  is  currently 
under evaluation in cosmetic products.  

  Detailed exposure data are not always available and, therefore, as for any group of chemicals, it 

may be problematic for a risk-based approach. 

  There  is  a  theoretical  possibility  for  inconsistencies  in  evaluation  e.g.  of  co-formulants  for 
biocides and plant protection products, which are also regulated under REACH. ED assessment of 
co-formulants is not foreseen for plant protection products, whereas it is for biocides. Moreover, 
biocides authorities could reach a different conclusion than the REACH authorities for the same 
substance  unless  coordination  is  ensured.  Gaining  access  to  information  could  be  an  issue  for 
applicants under the Biocidal Products Regulation  (BPR), since  suppliers  may not be  willing  to 
grant access to data generated as part of consortia under REACH. 

  Removal of an exemption from authorisation for the use of some substances may be a problem if 
suitable substitutes are not available within the envisaged timeframe for sunsetting the  use (e.g. 
more flexibility needed in authorisation of the use of DEHP in medical devices, including blood 
bags, while current alternatives do not match the performance of DEHP). 

  There are inconsistencies regarding regulation at national and EU level. For example, France has 
regulated certain EDs more severely than at EU level. Several categories of food contact materials 
are  not  yet  harmonised  by  specific  EU  measures  and  although  in  that  case  national  provisions 
apply,  not  all  national  provisions  take  EDs  into  consideration.  The  new  Mutual  Recognition  of 
goods Regulation allows free circulation in such cases. 

  Many  EU  regulatory  frameworks  lack  ED-specific  provisions:  food/feed  additives,  food  contact 
materials,  veterinary  drugs,  cosmetic  products,  toys,  workers  regulations,  consumer  products, 
hazardous substances in electric and electronic equipment, waste.  

  Lack of understanding/assessment of aggregate exposure and mixed (combined) exposure, which 

may lead to insufficient protection. 

  Lack of a chemical grouping approach for identification and regulation  of similar  substances  to 

speed up evaluation and to avoid regrettable substitutions (e.g. case of bisphenols). 

  There  is  a  lack  of  adequate  test  methods  and  therefore  there  is  a  need  to  invest  more  in  New 
Approach  Methodologies.  Authorities  should  consider  accepting  more  alternative  methods  to 
increase the depth of their data sets. 

  Where  regulations  technically  allow  for  ED  management,  test  requirements  for  EDs  are 

inadequate (REACH, pesticides, biocides, and medical devices). 

  The process between ED identification and regulation under REACH takes many years and this 

leads to protection gaps (e.g. vulnerable groups). 

  Protection gaps: protection of children is particularly incoherent (e.g. bisphenol A is not banned in 
all baby food containers). Similarly, the foetus is not protected as pregnant women are exposed to 
substances via their food. 

54 

 
 
  Sector-specific  identification  of  EDs  leads  to  duplication  of  work  with  potentially  inconsistent 
outcome, thus creating regulatory uncertainty and ambiguity for the industry. There is a perceived 
overlap between substances that are used as biocides under the Biocidal Products Regulation and 
preservatives in the Cosmetic Products Regulation. 

  EU  legislation  and  national  authorities  have  insufficient  controls  on  the  safe  use  of  recycled 
materials  (e.g.  recycling  plastic  in  food  contact  materials  versus  recycled  paper  and  board  food 
packaging;  products  containing  chemicals  that  now  are  restricted  or  banned;  REACH  sets 
different standards for cadmium content in virgin and recovered rigid PVC; different standards for 
lead and DEHP in virgin and recycled PVC). 
It  is  key  to  achieve  a  degree  of  harmonisation  between  risk  assessment  processes  at  EU  and 
international level. 

 

  REACH  struggles  to  capture  the  environmental  impact  of  substances  in  food  contact  materials 

and cosmetic products.  

  There is the need to dedicate more resources to enforcement to block the flow of non-compliant 

products in the market. 

  Some substances are active on the endocrine system but have no negative effects. We are lacking 
studies to differentiate these substances from those that do have negative effects. At international 
level, only 66 substances are recognised as EDs. 
*Respondents to all three surveys (citizens, stakeholder and SME surveys) were self-selected and thus not 
necessarily representative of the full range of views of these groups. 

55 

 
 
 
 
4.5

  Coherence with non-EU jurisdictions 

Q2.  To  what  extent  is  the  regulation  of  EDs  in  the  EU  coherent  with  international  legal 
obligations (e.g. WTO) and regulatory approaches in other jurisdictions? What are the impacts 
of incoherencies and overlaps? 

4.5.1  Differences across jurisdictions 

The  EU  framework  for  assessing  and  managing  chemicals  is  recognised  globally  as  the  most 
ambitious in its objectives to achieve a high level of protection for human health and environment42. 
Compared  to  other  jurisdictions,  the  EU  legal  framework  for  testing  and  assessment  of  chemicals 
places a bigger burden on the chemicals industry than on governmental institutions.  

Common  to  many  jurisdictions  is  the  fact  that  the  risk  posed  by  EDs  is  the  subject  of  general 
chemicals legislation, as well as specific regulatory domains such as plant protection products, food 
legislation,  pharmaceuticals  etc.  (Milieu  Ltd  et  al.,  2017;  UNEP  IPCP,  2017).  Plant  protection 
products are subject to regulations and restrictions in all major global jurisdictions. Assessment values 
(acceptable  daily  intakes)  applied  for  pesticide  residues  are  rather  uniform  across  different 
jurisdictions, which is probably the result of the internationally harmonised procedures for the hazard 
characterisation of pesticides (Milieu Ltd et al., 2017). The Codex Committee on Pesticide Residues, 
for example, operating under the umbrella of FAO and WHO, is responsible for establishing Codex 
Maximum Residue Limits (CXLs) for pesticide residues in specific food items or in groups of food, as 
well  as  providing  international  standards  for  food  safety  and  fostering  international  trade43.  The  US 
Endocrine  Disruptors  Screening  Program  uses  information  on  endocrine  activity  or  exposures  to 
prioritise  screening  and  testing  programs  (EC  2016b).  A  similar  approach  is  used  in  the  EU  for 
general chemicals. ECHA screens chemical substances in their databases for available information on 
ED  properties,  combined  with  methods  such  as  Quantitative  Structure-Activity  Relationships 
(QSARs)  and  read-across44.  The  screening  serves  for  setting  priorities  for  further  regulatory  action 
(for  which  tonnage  information  can  be  taken  into  account  as  well),  such  as  setting  up  the  REACH 
Community Rolling Action Plan for Substance Evaluation45 or to develop the regulatory management 
options46 for a (group) of substance(s).  

4.5.2 

International legal obligations 

International  laws,  such  as  the  Stockholm  Convention  on  Persistent  Organic  Pollutants  (POPs),  as 
well  as  internationally  developed  guidelines  and  standards  on  chemical  safety  (e.g.  the  Globally 
Harmonised System on Classification and Labelling, and Codex Maximum Residue Limits (MRLs)) 
do not contain specific provisions on EDs. By establishing specific approaches to assess and regulate 
EDs,  the  EU  applies  higher  standards  of  human  health  and  environmental  protection,  compared  to 
those  established  by  international  standards.  WTO  rules  allow  higher  standards,  provided  they  are 
duly  notified  and  scientifically  justified.  The  EU  has  regularly  notified  new  measures,  including 
changes in legal provisions, restrictions and safety standards on EDs. Starting from 2014, a specific 
trade concern was raised by Argentina, China, Ecuador, Guatemala, India, Panama, Paraguay, and the 
United States of America with the support of another 38 members in relation to the EU’s intention to 
publish a road map outlining different options to assess, classify and regulate EDs in the context of 

42SWD(2019) 199 
43http://www.fao.org/fao-who-codexalimentarius/thematic-areas/pesticides/en 
44https://echa.europa.eu/screening 
45https://echa.europa.eu/information-on-chemicals/evaluation/community-rolling-action-plan/corap-table 
46https://echa.europa.eu/substances-of-potential-concern 

56 

 
 
                                                      
the  Plant  Protection  Products  Regulation  (PPPR)47.  WTO  members  have  since  then  repeatedly  and 
frequently challenged the consistency of the generic risk approach in the PPPR with the obligation of 
the Agreement on the Application of Sanitary and Phytosanitary Measures (SPS agreement) to base 
more restrictive measures on “an assessment of the risks to human, animal or plant life or health”. The 
EU  maintained  in  the  meeting  of  the  WTO  Committee  on  Sanitary  and  Phytosanitary  Measures  in 
November  201947  that  the  criteria  for  EDs  are  legitimate  and  motivated  by  scientific  and  societal 
concerns (low level of tolerance to risk from residues of pesticides in the EU). Moreover, criteria for 
ED identification are in line with the IPCS/WHO definition. The debate has continued ever since and 
remains unresolved, although it has not escalated to a formal dispute.  

Several  WTO  members  also  requested  the  European  Union  to  harmonise  its  import  tolerances  for 
active substances which were not re-approved with existing levels (MRLs with Codex standards) to 
allow  for  trade  to  continue  in  line  with  the  SPS  agreement.  In  response,  the  EU  has  clarified  that 
whereas  the  use  of  substances  falling  under  the  exclusion  criteria  was  not  allowed  in  the  European 
Union,  import  tolerance  requests  would  be  nevertheless  processed  under  the  MRL  Regulation  (EC) 
396/2005, and a risk assessment would be carried out by an evaluating EU Member State and EFSA47. 
So far, no MRL has been reduced solely due to a substance meeting the exclusion criteria.  

47Specific Trade Concern (STC) ID 382. http://spsims.wto.org/en/SpecificTradeConcerns/View/382 

57 

 
 
 
                                                      
5  EFFECTIVENESS 

  Some endocrine disruptors can be identified using regulatory test guidelines, while for others 
methods  are  still  under  development  and  require  validation.  The  Commission  is  funding 
research  into  developing  new  methods  and  promoting  their  adoption  (once  validated)  as 
OECD Test Guidelines. 

  Data requirements under the Plant Protection Products Regulation (PPPR), Biocidal Products 
Regulation  (BPR)  and  REACH  are  being  updated  to  include  already  existing  OECD  test 
guidelines  relevant  to  ED  assessment,  in  particular  to  include  the  so-called  ‘mechanistic’ 
tests, which can pinpoint a specific endocrine activity. 
It is too early to assess the effectiveness of the PPPR and BPR in protecting health and the 
environment, since only a limited  number of substances have been identified  as EDs or not 
being EDs according to the criteria for identifying EDs adopted in 2018.  

 

  Under  REACH  all  substances  registered  by  June  2018  have  been  screened  for  possible 
endocrine  activity  as  far  as  possible  based  on  structural  alerts,  grouping  approaches  and 
existing data. Seventeen substances have been identified as Substances of Very High Concern 
(SVHC)  so  far,  due  to  their  endocrine  disrupting  properties  with  respect  to  human  health 
and/or the environment. However, only octylphenol, nonylphenol and their ethoxylates have 
been restricted under REACH with explicit reference to their endocrine disrupting properties. 
Other  restricted  substances,  which  are  possibly  endocrine  disruptors,  have  been  restricted 
without  explicit  reference  to  ED  properties  or  due  to  other  toxicities  (e.g.  organo-tin 
compounds). 

  Under REACH, inclusion of endocrine-disrupting effects as a concern regarding substances in 
the Candidate List triggers additional provisions for risk assessment (Chemical Safety Report) 
and risk communication (Safety Data Sheets) and requires specific consideration of endocrine 
effects in authorisations. 

  Some  pieces  of  sector  specific  legislation  can  take  into  account  the  identification  of  EDs 
under the BPR or PPPR, or the identification of substances under REACH as SVHC with ED 
properties. However, other sectorial legislation such as food contact materials, food additives 
and  cosmetic  products  have  further  requirements  for  products  or  sectors  they  regulate  but 
these  do  not,  as  yet,  specifically  address  endocrine  disruption,  hindering  the  systematic 
consideration  of  endocrine  disrupting  properties  for  substances  regulated  only  in  these 
specific areas.  

  Due  to  the  animal  testing  ban  in  the  cosmetics  sector,  as  for  many  other  toxicological 
endpoints an issue arises in relation to the need to demonstrate an adverse effect for an ED, 
which currently requires in vivo testing.  
Identification  of  EDs  is  currently  mainly  based  on  animal  testing.  New  approach 
methodologies  need  to  be  developed  and  integrated  into  the  regulatory  assessment  process. 
This  will  not  only  reduce  the  need  for  animal  testing,  but  also  increase  the  efficiency, 
relevance and reliability of the assessments. 

 

  A  “one  substance-one  assessment”  approach  was  seen  by  many  stakeholders  as  a  way  of 
increasing  the  effectiveness  of  regulatory  procedures  while  avoiding  potential  discrepancies 
in ED identification. 

  Communication  on  the  presence  of  EDs  in  products  is  required  under  REACH  and  the 
Biocidal  Products  Regulation.  However,  stakeholders  report  that  information  is  difficult  to 
find and to understand. They call for more and better information on EU activities regarding 
EDs. 

  For some EDs, environmental monitoring data and/or human biomonitoring data has provided 
evidence  that  restriction  measures  have  been  successful  in  reducing  exposure  levels. 

58 

 
 
 
 
 

Monitoring  data  can  also  provide  information  on  relevant  mixtures  of  EDs  in  the 
environment, wildlife and humans.  
In  relation  to  health  and  environmental  impacts  an  increase  in  the  main  non-communicable 
diseases/disorders that are suspected to be associated with exposures to endocrine  disrupting 
substance has been observed. However, it is difficult to conclude to what extent exposure to 
EDs from manufactured products contributes to the observed adverse effects. Consequently, it 
is not possible to draw firm conclusions regarding the effectiveness of legislation on EDs in 
reducing the increased incidence of those diseases.   

  Regarding  vulnerable  groups,  the  involvement  of  the  endocrine  system  in  the  control  of 
processes  such  as  embryonic  development,  puberty,  pregnancy  or  menopause  puts  foetuses, 
infants,  adolescents,  pregnant  woman  and  elderly  at  higher  risk  regarding  endocrine 
disruption.  It  is  important  that  data  requirements  for  ED  assessment  include  methods  that 
address these sensitive life stages. 

  Knowledge of the way in which substances exert their effects is important when carrying out 
the  assessment  of  mixtures,  specifically  when  considering  potential  additive  or  synergistic 
effects.  This  is  particularly  relevant  in  the  context  of  ED  assessment,  i.e.  knowledge  of  the 
(endocrine) modes of action of the respective components of a mixture facilitates an accurate 
assessment. 

Q3  To  what  extent  has  EU  legislation  been  effective  in  identifying  endocrine  disruptors  and 
managing  risks  related  to  their  exposure  across  different  legal  frameworks,  ensuring  the 
protection of human health and the environment? 

It is important to bear in mind that many substances may have more than one hazardous property and 
indeed this is often the case with EDs since the adverse effect associated with the endocrine mode of 
action might also be reproductive toxicity or carcinogenicity, including by the same mode of action 
(e.g. DEHP and other phthalates have been identified as ED and for reproductive toxicity caused by 
the same ED mode of action). EDs might also be persistent, bioaccumulative and toxic (PBT) or very 
persistent,  very  bioaccumulative  (vPvB).  Risk  management  measures  may  already  have  been  taken 
due to the substance’s other hazardous properties (e.g. phthalates). If these measures are the maximum 
that can be taken then there is no further impact of identifying the substance as an ED. However, in 
other cases, the identification of a substance as ED in addition to other toxicities (e.g. due to different 
effects  or  modes  of  action)  may  lead  to  a  need  to  apply  further  risk  management  measures.  In 
addition, not all EDs for human health will be identified as CMRs and identification as an ED for the 
environment may also trigger additional risk management measures. In the future, EDs with adverse 
effects other than  reproductive toxicity  or carcinogenicity may be identified  once  methods  to detect 
different related adverse effects and their modes of action are available. 

  Current process of ED identification 

5.1
In relation to ED identification the critical point is the availability of suitable, relevant and validated 
methods  to  test  substances  for  endocrine  disrupting  properties.  The  European  Commission  supports 
the development of methods at the international level so that the data generated with the methods will 
be  accepted  globally  under  the  mutual  acceptance  of  data  (MAD)  agreement  which  is  both  cost 
efficient for European businesses and prevents the unnecessary repetition of animal tests. The OECD 
test  guidelines  programme  has  been  striving  for  many  years  (since  the  mid-1990s)  to  develop  and 
validate  appropriate  tests  which  investigate  possible  ways  in  which  the  endocrine  system  can  be 
perturbed  and  consequently  cause  an  adverse  effect.  Test  guidelines  have  been  developed  in 
laboratory  animals  (fish,  amphibians  and  mammals)  as  well  as  in  vitro  assays  in  mammalian  cells. 
The  OECD  Conceptual  Framework  for  the  testing  and  assessment  of  endocrine  disruptors  currently 

59 

 
 
 
refers  to  over  30  test  guidelines  which  can  be  used  (together)  to  investigate  endocrine  disrupting 
properties  of  a  substance  (OECD,  2018).  The  methods  focus  on  interference  with  estrogen  (E)  and 
androgen (A) pathways including the process of steroidogenesis (S) (production of steroid hormones 
such  as  estrogen  and  testosterone)  and  some  tests  can  also  identify thyroid  (T)  hormone  disruption, 
together often referred to as the EATS pathways or modes of action. It is recognised that the toolbox 
of  available  tests  is  not  yet  complete  and  intensive  work  is  ongoing  through  EU-funded  research 
programmes  such  as  the  current  5-year  EURION  project48.  EURION  is  a  cluster  of  eight  research 
projects  funded  with  €50  million  by  the  European  Commission’s  Horizon  2020  Research  and 
Innovation Programme, the largest public funding of this type of research in Europe. Each project in 
the  cluster  is  focusing  on  a  different  aspect  of  new  testing  and  screening  methods  identifying  EDs. 
The projects focus on improving methods for the identification of thyroid hormone disruptors, as well 
as  developmental,  metabolic  disorders  and  female  reproductive  disorders  caused  by  endocrine 
disruption. There is also a project specifically exploring cross-species extrapolation of thyroid effects 
from fish to mammals.  

The  Commission  is  also  promoting  the  adoption  of  the  methods  (once  validated)  as  OECD  Test 
Guidelines  and  has  contributed  to  the  development  of  standardised  and  internationally  agreed  test 
methods  through  grants  to  the  OECD  test  guideline  programme.  For  the  periods  2015/2016  and 
2017/2018  a  contribution  of  around  €1  million  was  given  twice  towards  the  development  of 
guidelines  for  the  testing  of  endocrine  disruptors  either  through  grants  to  the  OECD  or  through 
framework contracts. The contribution also benefitted the work on Integrated Approaches to Testing 
and  Assessment  (IATA)  and  Adverse  Outcome  Pathways  (AOP),  which  are  expected  to  play  an 
important  role  in  defining  future  alternative  testing  approaches49.  In  addition,  the  JRC’s  EURL 
ECVAM in collaboration with the network of validation laboratories in the EU Member States (EU 
NETVAL)50,  is  carrying  out  the  validation  of  17  in  vitro  methods  drawn  from  the  OECD  scoping 
document 207 (OECD, 2017) which can then be used to identify substances that interfere with thyroid 
hormone production and action. 

In  summary,  some  endocrine  disruptors  can  be  identified  using  regulatory  test  guidelines  whilst  for 
others, methods are still under development and require validation. These tests are the basis for ED 
identification  (where  required)  under  any  existing  EU  regulatory  instruments  related  to  chemical 
safety  assessment.  In  practice,  to  date,  identification  of  endocrine  disruptors  has  also  relied  on 
information  derived  from  non-regulatory  studies  in  the  published  scientific  literature.  In  2016,  the 
European  Commission  commissioned  a  study  on  commonalities  and  differences  in  approaches  for 
testing and assessment of endocrine disruptors within the EU and among relevant international trading 
partners  (Brunel  University  London  and  DTU  Food  National  Food  Institute  Denmark,  2016).  The 
study  compared  the  approaches  for  the  regulatory  screening,  testing  and  assessments  of  substances 
between the legal frameworks, and used cases studies to demonstrate commonalities/differences. The 
analysis  confirmed  that  the  current  approach  of  considering  data  from  scientific  literature  alongside 
those  obtained  by  regulatory  testing  was  needed  (5  out  of  the  8  EDs  used  as  case-studies  were 
discovered through research activities, and not regulatory assessment). 

Many  of  the  current  activities  at  OECD  level  and  EC  level  are  addressing  the  concerns  of  the 
stakeholders who replied to the survey (Box 5.1).  

48EURION project: https://eurion-cluster.eu 
49SWD(2018) 58 
50https://ec.europa.eu/jrc/en/eurl/ecvam/alternative-methods-toxicity-testing/eu-netval 

60 

 
 
 
                                                      
Box 5.1 Stakeholder views on available regulatory test methods* 

Regarding  available  regulatory  test  methods,  the  need  of  test  methods  for  assessment  of 
endocrine  pathways  beyond  ‘EATS’  was  highlighted  most  often  by  respondents  (49%  of  the 
responses).  The  second  most  commonly  highlighted  point  was  about  the  need  to  develop  non-
animal tests (32% of the responses), particularly in relation to the animal testing ban for cosmetic 
products. The need for methods investigating pathways beyond ‘EATS’ was the main concern of 
academic/research  institutions,  civil  society  organisations,  public  authorities  and  trade  unions. 
Business  associations  and  companies/business  organisations  would  focus  on  the  need  for  non-
animal tests. 

The examples of endocrine modalities beyond EATS included; adrenal and retinoid pathways; the 
neuroendocrine  axis;  and  the  immune  system  and  interference  with  hormones  associated  with 
metabolism disorders (obesity, diabetes) or developmental neurotoxicity. 
Some respondents referred to the need for specific types of test including: 

  Tests covering the whole life cycle of organisms including impact of EDs on aging 
  Tests on thyroid effects  
  Tests on species representing more widely environmental species including invertebrates 
  Tests on Absorption, Distribution, Metabolism and Excretion (ADME) 
  Several stakeholders also mentioned that current tests are not sensitive enough and should be 
further developed to include more sensitive endpoints. There was also reference to the doses 
at which tests are  run, cautioning against running tests  at too  low doses such that important 
effects are missed, whereas others are suggesting that tests also be run at low doses in order to 
detect low dose effects (which might be different from effects at high dose). 

  Some  respondents  mentioned  that  tools  such  as  Integrated  Testing  Strategies,  Defined 
Approaches,  Integrated  Approaches  to  Testing  and  Assessment,  or  Adverse  Outcome 
Pathways should be developed. 

*Respondents  to  all  three  surveys  (citizens,  stakeholder  and  SME  surveys)  were  self-selected  and  thus  not 
necessarily representative of the full range of views of these groups. 

As  described  in  the  state  of  play  (Annex  4),  there  are  currently  five  regulatory  instruments  that 
contain provisions related to endocrine disruptors. These are REACH, the BPR, the PPPR, the WFD 
and the medical devices Regulation. 

Criteria for ED identification are laid down for Biocidal Products and Plant Protection Products but 
not under REACH, which relies directly on the IPCS/WHO definition. The ability to detect endocrine 
disrupting  properties  under  the  three  pieces  of  legislation  is  limited  by  the  requirements  for  data 
generation  (see  4.1),  which  are  in  the  process  of  being  updated  for  ED  endpoints,  in  particular  to 
include the mechanistic assays (addressing stakeholders concerns (Box 5.2). 

61 

 
 
 
 
 
 
Box 5.2: Stakeholder views on data requirements* 

Over 70% of respondents consider the available regulatory tests insufficient to  identify EDs and 
that  the  data  requirements  laid  down  in  relevant  legislation  (REACH,  Biocidal  Products 
Regulation,  Plant  Protection  Products  Regulation)  are  also  insufficient.  This  view  point  was 
shared amongst all the stakeholder groups. 

Regarding  data  requirements,  many  respondents  to  the  stakeholder  survey  (from  public 
authorities  and  academic/research  institutions)  stated  that  they  have  to  be  adapted  to  include 
mechanistic data. Some respondents primarily from civil society organisations also suggested to 
make full use of “independent” research, including when it does not follow OECD guidelines or 
GLP, as a way to improve the effectiveness of the BPR, PPPR and REACH in identifying EDs.  

Regarding the BP and PPP Regulations views expressed by public authorities in the stakeholder 
survey included: 

  Data requirements should be updated to require the most modern test guidelines including the 

 

ED-sensitive endpoints  
Investigations should go beyond the EATS modalities, for example including immunotoxicity 
as a core data requirement. 

  For  PPPs,  thyroid  effects  should  be  addressed  in  non-target  organisms  and  there  should  be 
requirements for top tier definitive studies in fish (MEOGRTS) and amphibians (LAGDA) at 
level 5 of the OECD Conceptual Framework. 

  Data requirements for co-formulants of PPPs should be specified in a simpler way. 

Regarding  the  REACH  Regulation  views  drawn  from  the  stakeholder  survey  included  the 
following: 

  The development of screening strategies and a better integration of the latest test methods was 

recognised as a need by civil society organisations 

  Several  respondents  (from  public  authorities,  civil  society  organisations  and  business 

associations) suggested the inclusion of mechanistic data for low tonnage substances 

  With  regard  to  data  requirements  for  the  environmental  assessment,  one  respondent  pointed 

out that there are no explicit data requirements for ED relevant aquatic vertebrate tests 

  A  public  authority  mentioned  that  thyroid-specific  endpoints  only  exist  for  amphibians  and 

should also be included in the fish tests (FELS/FSDT),  

  A  business  association  stressed  that  applying  the  same  test  strategy  as  for  PPPs  and  BPs  to 
REACH  would  lead  to  an  enormous  amount  of  animal  testing,  with  also  severe  delays  and 
economic burdens. 

  Several civil society organisations suggested that peer-reviewed scientific literature should be 

given as much weight as validated tests.  

*Respondents  to  all  three  surveys  (citizens,  stakeholder  and  SME  surveys)  were  self-selected  and  thus  not 
necessarily representative of the full range of views of these groups. 

Moreover,  the  adaptive  nature  of  the  endocrine  system  requires  a  combination  of  tests  for  ED 
identification, which currently mostly rely on animal testing and require considerable cost and time to 
produce the necessary data (Browne et al., 2020). Most of the available in vivo toxicity test guidelines 
currently  required,  although  not  specifically  designed  for  the  purpose  of  investigating  endocrine 
disrupting  properties,  do  include  some  endocrine-related  parameters.  These  tests  have  to  be  carried 
out  for  biocides  and  pesticides  and  higher  tonnage  REACH  substances  to  investigate  toxicity  in 

62 

 
 
 
 
 
general,  independent  of  endocrine  disruption.  However,  to  reach  a  conclusion  on  endocrine 
disruption,  additional  tests  will  likely  be  required,  covering  additional  evidence  of  specific 
interactions  with  the  endocrine  system  (so-called  mechanistic  studies).  Sometimes  this  may  also 
include the need to repeat an old study in accordance with updated test guidelines incorporating more 
sensitive  markers  of  endocrine  disruption.  The  amount  of  additional  testing  to  be  carried  out  thus 
depends on the amount of reliable data available for the substance and the data gaps that need to be 
filled to draw a conclusion. 

An example of a potential increased cost due to ED testing would be the difference between the cost 
of  the  basic  design  of  an  Extended  One  Generation  Reproductive  Toxicity  Study  (OECD  TG  443) 
compared  with  the  additional  cost  of  extending  the  study  to  two  generations  and/or  including 
additional groups of animals to investigate effects of the substance on neurological development. The 
basic design of the EOGRTS was included in the REACH data requirements in 2015. Extensions are 
triggered in case of a concern, e.g. for endocrine disruption. In a study commissioned by ECHA on 
the  analysis  of  capacities  and  capabilities  of  laboratories  to  conduct  the  OECD  TG  443,  contract 
research organisations stated that the cost of the basic study design in 2015 to be on average around 
430,000€  (Risk  &  Policy  Analysts  Limited,  2015).  Extension  of  cohort  1B  (to  test  for 
reproduction/development)  increases  the  cost  by  20%  (median  value)  compared  to  the  basic  study 
design,  the  developmental  neurotoxicity  cohorts  2A  &  2B  increase  the  cost  by  30%,  the 
developmental immunotoxicity cohort 3 by 15%, and a full study design by 60%. Examples of costs 
of mechanistic methods specifically designed for endocrine testing, are in 2020, about 170,000 € for 
the  uterotrophic  and  Hershberger  assays  (combined).  For  the  Amphibian  Metamorphosis  Assay  an 
estimation  of  75,000  USD  is  given  in  OECD  GD  150  (version  2012).  Regarding  in  vitro  testing 
(OECD TG 455, 456, 458, OPPTS 890.1200), the average cost in 2020 of each test goes from 2000 to 
20,000€  depending  on  the  test  or  service  provider.  In  relation  to  the  time  taken  to  conduct  the  test, 
contract research organisations have recently indicated durations of around 9 months to conduct the 
mechanistic in vitro tests and around 20 to 24 months for the in vivo assays such as the uterotrophic 
and  extended  one  generation  study  in  rodents  and  up  to  28  months  for  an  extended  one  generation 
reproductive  toxicity  test  in  fish  (medaka)  (MEOGRTS)  or  a  larval  amphibian  growth  and 
development  study  (LAGDA)51.  However,  the  estimated  time  periods  do  not  consider  possible 
limitations of testing capacity of laboratories, which is an important factor to take into account when 
updating data requirements.  

Regarding the REACH data requirements for environmental assessment, chronic toxicity data on fish 
are required for tonnages above 100 tonnes, but will often be based on a fish early life-stage (FELS) 
test  which  does  not  allow  for  ED  identification,  as  it  does  not  include  any  ED-related  endpoints. 
Therefore, additional testing would be required for ED identification. In addition, for thyroid-specific 
effects,  an  amphibian  test  would  be  needed  as  there  is  no  thyroid-related  endpoint  in  the  fish  test 
guidelines.  However,  this  should  change  as  several  research  projects  funded  by  the  European 
Commission are investigating the possibility to add thyroid-related endpoints to the fish tests. 

Although  data  requirements  under  the  PPPR,  BPR  and  REACH  are  still  in  the  process  of  being 
updated, available or newly generated data sets, including studies reported in the published scientific 
literature,  have  allowed  some  substances  to  be  identified  as  EDs  under  each  of  these  regulations  as 
explained further below.  

51Response to request for information from EFSA provided on 30th June 2020 

63 

 
 
                                                      
Box 5.3: Stakeholder views on animal testing* 

With  regard  to  the  use  of  in  vitro  and/or  in  silico  methods,  a  majority of  stakeholders  think  that 
they are not used systematically enough  to prioritise further investigations (80  agree, 7  disagree, 
and 38 neither agree nor disagree). In particular, they commented that: 

 
 

 

 

 

in vitro and/or in silico methods are not easily accepted by competent authorities 
there are not enough in vitro and/or in silico methods available (they would be easier to use if 
more were available and could be combined), and available ones are not reliable or predictive 
enough. Some stakeholders also mentioned the lack of expertise in these methods as a limiting 
factor for their use. Several stakeholders call for the development of guidance for the use  of 
such methods. 
if in vitro and/or in silico methods are used for prioritisation purposes, they might not need to 
be  OECD  Test  Guidelines.  It  might  be  sufficient  for  the  methods  to  meet  some  acceptance 
criteria. 
in  vitro  and  in  silico  methods  should  also  be  used  more  systematically  to  support  the 
development of grouping approaches 
in vitro and/or in silico data cannot outweigh in vivo data to identify ED potential (not used to 
discard evidence of adverse effects) 

A  bit  more  than  half  of  the  stakeholders  expressing  an  opinion  (54%)  think  that  the  impact  of 
assessing chemicals for endocrine disrupting properties on animal welfare is minimised in the EU 
to the extent possible. This opinion is globally shared by all the stakeholder groups, except the civil 
society organisations which mostly think it is insufficiently minimised. Amongst the citizens, 37% 
think that animal testing for endocrine disrupting properties in the EU is insufficiently minimised, 
whereas  28%  consider  animal  testing  to  be  fully  minimised  (5%)  or  minimised  to  the  extent 
possible (23%). 

  Many  stakeholders  mentioned  that  the  best  way  to  minimise  the  use  of  animals  would  be  to 
apply the one substance –one assessment approach, allowing data to be used across regulatory 
sectors.  Moreover,  this  could  be  made  more  efficient  and  transparent  through  a  more 
centralised  approach  to  testing  (based  on  industry  fees  but  managed  by  independent 
authorities). 

  A  common  data  base  of  registration  data  covering  all  regulatory  regimes,  accessible  to  both 

applicants and regulatory bodies was mentioned as another tool to reduce animal testing. 

  A  stakeholder  suggested  to  allow  cross-class  extrapolations  among  vertebrates,  highlighting 

that the endocrine system is highly conserved among vertebrates.  

  Some stakeholders suggested that the creation of a suspected category for EDs would lead to 
minimization  of  exposures  and  less  use  of  animal  tests,  stating  that  today  many  tests  are 
carried out to defend continued use of a chemical. 

  A stakeholder suggested to further develop models such as the ToxCast ER bioactivity model 
for  other  modalities  and  improve  the  predictivity  of  models  such  as  the  ToxCast  AR 
bioactivity model. 

*Respondents  to  all  three  surveys  (citizens,  stakeholder  and  SME  surveys)  were  self-selected  and  thus  not 
necessarily representative of the full range of views of these groups. 

Regarding the stakeholder statement that “the best way to minimise the use of animals would be to 
apply  the  one  substance–one  assessment  approach,  allowing  data  to  be  used  across  regulatory 
sectors”, it should be highlighted that under REACH and the Biocidal Products and Plant Protection 
Products Regulations, the sharing of data from vertebrate animal tests is an obligation. 

64 

 
 
 
 
 
 
5.2

  Biocidal Products and Plant Protection Products Regulations  

The  PPPR  and  BPR  introduced,  in  2009  and  2012  respectively,  an  approach  that  active  substances 
identified as EDs cannot be approved – unless very limited derogation possibilities are met. Such an 
approach  is  already  applied  to  substances  with  CMR  properties  (the  so-called  exclusion  or  cut-off 
criteria; see Section 3 and Annex 4).  

According to EFSA52, seven of the 57 ED assessments of active substances conducted so far under the 
PPPR resulted in the active substances being identified as EDs with respect to human health (Table 
5.1). Of the remaining 50, there was no evidence of endocrine disruption for 17, further information 
was  requested  for  20  substances,  the  ED  assessment  was  waived  for  12  substances  for  different 
reasons  and  one  assessment  is  still  in  progress.  The  55  assessments  conducted  with  respect  to  the 
environment (non-target organisms) concluded that three active substances had endocrine disrupting 
properties whereas five did not, eight assessments were waived and 39 required further testing.  

According to ECHA53, the Biocidal Products Committee (BPC) has delivered 17 opinions on biocidal 
active substances since the criteria came into action (June 2018). In these opinions, three substances 
were  concluded  to  meet  the  ED  criteria  for  human  health  and/or  non-target  organisms,  and  three 
substances  were  concluded  not  to  meet  the  ED  criteria.  Of  the  remaining  11  substances,  the  BPC 
could not conclude due to the absence of sufficient data. However, for assessment reports submitted 
before 1 September 2013, the evaluating Competent Authority has to conclude based on the already 
available  data  and/or  the  data  provided  by  the  applicant.  Where  this  data  is  insufficient  to  reach  a 
conclusion,  the  BPC  may  conclude  in  its  opinion  that  no  conclusion  could  be  drawn54.  In  addition, 
when  the  substance  is  already  non-approved  (due  to  meeting  other  exclusion  criteria)  no  additional 
data are requested for the ED assessment. 

An additional 12 substances have already been discussed by the BPC Working Groups without having 
progressed  to  the  BPC.  In  the  Human  Health  working  group, 11  substances  have  been  discussed:  4 
substances  were  concluded  to  not  meet  the  criteria.  For  the  remaining  7  substances  no  conclusion 
could be drawn,  although in some cases there  could be technical limitations to providing additional 
data. In the Environment Working Group, 10 substances have been discussed: for 1 substance the ED 
assessment was waived, while for the remaining 9 substances no conclusion could be drawn due to the 
absence  of  sufficient  data.  In  most  cases,  additional  data  will  need  to  be  generated  in  order  to 
conclude on the ED properties for non-target organisms, particularly for non-mammals. 

Table 5.1: Outcomes of active substance assessments for endocrine disrupting properties under the PPPR 
(as of August 2020) 

Properties 

Substances 
assessed  for  ED 
properties 

Substances 
identified 
as ED  

Substances 
not  meeting 
the 
ED 
criteria 

Human Health 
Environment  

57 
55 

7 
3 

17 
5 

No 
conclusion 
possible 
(further 
data  may 
be 
required) 

20 
39 

Assessment 
waived 

Assessment 
in progress 

12 
8 

1 

52Response to request for information from EFSA provided in August 2020 
53Response to request for information from ECHA provided in September 2020 
54CA-March18-Doc.7.3a-final- EDs- active substances under assessment  

65 

 
 
 
 
 
 
                                                      
Table 5.2: Outcomes of active substance assessments for endocrine disrupting properties under the BPR 
(as of September 2020) 

Substances 
assessed for ED 
properties 

Substances 
identified  as 
ED  

Substances  not 
meeting  the  ED 
criteria 

conclusion 
(further 
be 

No 
possible 
data  may 
required) 

Assessment 
waived 

BPC 
Opinions 
(Human  Health  and 
Environment) 
BPC Human Health 
WG  
BPC  Environment 
WG 

17 

11 

10 

3 

3 

4 

11 

7 

9 

1 

The experience gained so far demonstrates that for some substances the existing data were sufficient 
to  reach  a  decision  but  for  many  the  existing  data  were  insufficient.  This  confirms  that  the  data 
requirements for the Regulations need to be updated in order to increase the likelihood that a decision 
on endocrine disrupting properties can be made on the basis of the data package presented as part of 
the approval or renewal applications. This should significantly reduce the frequency of the necessity 
to  ‘stop  the  clock’  to  request  further  information  related  to  ED  properties  which  slows  down  the 
regulatory  process.  An  update  of  the  data  requirements  has  been  initiated  under  the  BPR  and  the 
PPPR  as  described  in  the  state  of  play  (Section  3  and  Annex  4).  Since  the  criteria  only  came  into 
effect in 2018 it may be considered too early to assess the effectiveness of the ED criteria for the BP 
and PPP Regulations  (a view supported by many of the respondents to the stakeholder survey)  – in 
fact, the Regulations establishing the criteria foresee a review by 2025 (i.e. 7 years after they start to 
apply). However, 44 PPP active substances considered as EDs according to the WHO-UNEP Report 
of 2012 have been  already withdrawn from the  market due to other hazardous properties leading  to 
unacceptable  risks  to  human  health  and  the  environment55.  In  addition,  many  active  substance 
renewal/non-renewal  regulations  already  include  consideration  of  the  ED  aspect  in  light  of  the 
submitted dossier and criteria. 

In  summary, since  the  criteria  came  in  force  in  2018  any  pending  or  new  request  for  approval  of  a 
new active substance under the BP and PPP Regulations require an evaluation of endocrine disrupting 
properties. In addition, for active substances currently on the market, renewal of approvals is required 
on a regular basis (every 7 to 15 years), ensuring that all substances will be re-evaluated in light of 
new  scientific  information.  This  also  covers  the  assessment  of  endocrine  disrupting  properties, 
according  to  the  new  criteria,  and  renewal  processes  which  were  already  ongoing  when  the  new 
criteria  entered  into  force  but  were  still  pending.  Furthermore,  re-assessment  is  also  required  when 
new evidence emerges56. The data requirements under both regulations are currently being updated to 
enhance  the  possibility  to  identify  EDs  based  on  relevant  OECD  test  guidelines  within  the  OECD 
Conceptual  Framework.  A  (systematic)  review  of  the  literature  is  also  required  to  identify  relevant 
studies from the published scientific literature. Evaluations conducted since 2018 have demonstrated 
that it is possible to identify EDs, or the absence of ED properties, for a number of substances based 
on data already available within the dossiers supported by the published scientific literature, which is 
always considered since evaluations must be based on all available data (see Table 5.1). 

55SWD(2016) 211, Annex 9, p214 
56SWD(2019) 199, p64 

66 

 
 
 
 
 
 
 
 
 
                                                      
Box 5.4: Stakeholder views on effectiveness of BP and PPP Regulations as regards EDs*,** 
The proportion of each stakeholder group responding that the Regulations are not effective is presented in the graph below: 

  A viewpoint from companies/business organisations and business associations is that restrictions on use of some biocides based on their ED properties will decrease the 
availability of products and may increase the risk of an outbreak of resistant microbes. Similarly, for pesticides with the risk of pest resistance. This could have major 
adverse impacts on food production and price, with associated negative consequences on health, the environment and society as a whole. 

67 

0%10%20%30%40%50%60%70%80%90%100%BiocidesPesticidesBiocidesPesticidesBiocidesPesticidesBiocidesPesticidesBiocidesPesticidesBiocidesPesticidesBiocidesPesticidesprotection of consumersprotection of workersprotection of citizensprotection of wildlifeimprovement of theinternal marketenhancment ofcompetitiveness andinnovationpromotion of alternativesto animal testingOtherBusiness associationCompany/business organisationTrade unionCivil society organisationsAcademic/research institutionPublic authority 
 
 
 
 
  According to civil society organisations, slowness of the procedures is leaving many substances un-assessed (and thus still on the market).  
  Effectiveness of the BPR/PPPR is reduced by the (too) high level of evidence required to demonstrate endocrine properties of a substance. 
  There is a risk to buy on-line products from outside of the EU which may not comply with EU regulations which is a factor limiting the effectiveness of the regulations. 
  The same assessment strategy for identification of ED properties cannot be applied to the non-active substances in biocidal products or co-formulants under PPPR as data 

are not available and cannot be requested from applicants. 

*Answers are given as a percentage of respondents from each stakeholder group. For more details see Annex 2. 
 **Respondents to all three surveys (citizens, stakeholder and SME surveys) were self-selected and thus not necessarily representative of the full range of views of these 
groups. 

68 

 
 
 
5.3

  REACH 

Under REACH there are provisions for restricting or authorising the use of substances with endocrine 
disrupting  properties.  The  REACH  registration  database  contains  22,877  substances  (as  of  11  July 
2020)57. One of the principles of REACH is an increasing requirement for information on hazardous 
properties in accordance with potential for exposure, based on uses and production levels. The process 
of substance evaluation, however, allows for the evaluation of any substance based on concerns from 
existing data. 

The ED-related provision is introduced through Article 57(f), which allows endocrine disruptors to be 
identified  as  substances  of  very  high  concern  (SVHCs)  if  they  exhibit  serious  effects  that  are  of 
equivalent  concern  to  other  substances  of  very  high  concern  such  as  carcinogens,  mutagens  and 
reproductive toxicants (CMRs) (Category 1A/1B) or persistent, bioaccumulative and toxic substances 
(PBTs/vPvBs).  

Although criteria for the identification of EDs are not defined in the legal text of REACH, this has not 
prevented  substances  from  being  identified  as  EDs.  This  has  been  achieved  through  agreements  by 
Member State competent authorities to follow the IPCS/WHO definition and use the OECD guidance 
document  150  on  the  testing  and  assessment  of  endocrine  disruptors  (OECD,  2018)  with  their  own 
expertise  to  evaluate  existing  data  (including  non-regulatory  studies  in  the  scientific  published 
literature). Through the substance evaluation procedure of REACH, it is also possible to request the 
registrant to conduct additional studies listed in the OECD Conceptual Framework in order to clarify 
concerns on toxicity, including endocrine disrupting properties.    

As an action under the Community Strategy for EDs from 1999 a study was contracted by DG ENV 
in which an extensive literature search was carried out to identify substances that had been reported in 
the literature to be associated with endocrine activity either from  in vitro or in vivo studies. Around 
500  substances  were  identified  and  a  process  of  verification  of  the  validity  of  the  studies  was 
undertaken  through  expert  workshops.  Substances  were  categorised  according  to  the  presence  of 
endocrine activity in vitro or in vivo in at least one positive test. Further analysis revealed that many 
of the uses of these substances were already restricted under EU legislation in relation to their other 
hazardous properties (e.g. CMRs or PBTs/vPvBs).  

This list of substances along with other information (e.g. from the ChemSec SIN list58) fed into the 
ECHA screening approach59, 60 for REACH registered substances, which serves as a starting point for 
further  investigation  of  ED  properties  under  REACH  substance  evaluation  or  for  regulatory  action 
such  as  a  restriction  or  SVHC-identification/authorisation.  The  starting  pool  of  substances  for  all 
ECHA’s screening activities comprises approximately 130 000 substances in ECHA’s database. The 
screening  approach  also  uses  computational  tools  to identify  substances  with  chemical  structures  or 
sub-structures/functional  groups  related  to  the  structures  of  known  endocrine  disruptors  as  well  as 
searches  in  registration  dossiers  of  endocrine-related  terms  including  potentially  endocrine-related 
(adverse) effects. 

57https://echa.europa.eu/information-on-chemicals/registered-substances 
58https://echa.europa.eu/documents/10162/19126370/sin-list_analysis_en.pdf/6248cac0-ffa8-5a14-ae55-
93ace7ee9017 
59https://echa.europa.eu/documents/10162/19126370/common_screening_approach_en.pdf/b195b928-25ce-
4a1c-9eec-8f58ca724f58 
60https://echa.europa.eu/documents/10162/19126370/screening_definition_document_en.pdf/e588a9f8-c55e-
4412-a760-49ddbf7ac687 

69 

 
 
                                                      
In  this  manner,  substances  in  ECHA’s  database  have  been  screened  for  potential  endocrine  activity 
based on existing data in REACH registration dossiers but also, in some cases, the published scientific 
literature and those with indications of activity have been taken up by REACH competent authorities 
for further regulatory action.  

Screening information on potential ED properties of pre-registered substances in the tonnage range of 
1-10 tonnes per year was also made available by ECHA on their dissemination portal as part of the 
REACH Annex III inventory. Registrants of low tonnage substances could check prior to registration 
whether their substances were considered likely to have hazardous properties. Lower numbers of low 
tonnage substances were registered at the last registration deadline (end of May 2018) than originally 
expected.  While  reasons  for  a  lower  number  of  registrations  are  unknown,  it  could  be  hypothesised 
that  the  screening  information  provided  by  ECHA  may  have  discouraged  industry  from  registering 
such potentially hazardous substances. 

To support the effectiveness of the process of ED assessment an ED Expert Group has been set up to 
provide  an  informal  consultation  body  for  the  Member  States,  the  Commission  and  ECHA  on  all 
regulatory  assessments  related  to  EDs  under  REACH  and  the  BPR.  The  ED  Expert  Group  helps 
define the best testing strategy and data to be requested  in a substance evaluation decision  before  a 
substance  enters  the  formal  substance  evaluation  decision-making  process.  This  happens  during  the 
12-month period given to Member States to evaluate the substance, and therefore does not affect the 
duration  of  the  overall  process.  Besides  the  MS  experts,  the  ED  Expert  Group  includes  stakeholder 
organisations  as  observers  (representing  industry,  consumer  and  environmental  protection  groups, 
trade unions and animal welfare organisations). According to the endocrine disruptor assessment list 
on ECHA’s website61, the ED Expert Group has discussed 92 substances or group of substances under 
REACH or the BPR. Many substances are brought to the expert group before being moved to SVHC 
identification,  which  has  resulted  in  improved  dossier  quality  and  less  need  for  discussion  at 
Committee level. Member State Competent Authorities responsible for drafting the Annex XV dossier 
can decide to focus on either ED for the environment or ED for human health (or both) since often 
different  agencies  with  different  expertise  carry  out  each  type  of  assessment.  This  allows  Member 
States some flexibility in deploying their resources. In principle, this could lead to a lack of coherence 
on  the  data  sets  used  and  reduce  the  possibility  for  effective  read-across  between  the  human  health 
and  environmental  data,  which  should  be  used  together  in  a  weight  of  evidence  approach  to  reach 
decisions.  However,  in  most  cases  Member  State  authorities  consider  human  health  data  when 
assessing environmental properties and vice versa, and there is no evidence showing that separating 
the assessments is affecting the assessments. 

Substances  with  endocrine  disrupting  properties  are  identified  as  SVHC  if  the  substance  is  of  an 
equivalent level of concern (ELoC) to CMRs Cat. 1A/1B or PBT/vPvBs as specified in Article 57 (f) 
of the REACH Regulation. Lack of unanimous agreement in the REACH Member State Committee 
(MSC) of ECHA on identifying a substance as an SVHC under REACH and the need to refer such 
cases  to  the  Commission  can  be  seen  to  have  slowed  down  the  process  (as  highlighted  by  some 
stakeholders). However, through the decisions taken by the Commission (after a vote in the REACH 
Committee)  on  these  disputed  cases  and  by  judgements  of  the  Courts  in  Luxembourg,  a  common 
interpretation  has  started  to  emerge,  which  can  be  applied  by  the  MSC  in  future  cases  and  should 
increase the efficiency of the overall process. As of July 2020, 17 substances have been identified as 
endocrine  disruptors  of  equivalent  concern  to  SVHCs  for  either  human  health  (5  substances)  or  the 
environment (10 substances), plus 2 identified as ED for both human health and the environment. All 

61https://echa.europa.eu/ed-assessment 

70 

 
 
                                                      
the substances that have been agreed to be endocrine disruptors by ECHA’s Member State Committee 
have also been identified as SVHCs (i.e. ELoC) except for resorcinol. In the case of resorcinol, the 
MSC  opinion  that  the  substance  is  an  ED  of  ELoC  has  recently  been  referred  to  the  European 
Commission’s  REACH  Committee,  along  with  the  minority  position  disagreeing  with  the  opinion. 
Some  of  these  substances  were  already  listed  as  SVHCs  and  undergoing  authorisation  due  to  their 
other hazardous properties. Of those EDs placed on the candidate list, 6 have been transferred to the 
authorisation  list  (Annex  XIV).  Applications  for  authorisations  are  undergoing  or  have  undergone 
evaluations  by  ECHA’s  Committee  for  Risk  Assessment  (RAC)  and  Committee  for  Socioeconomic 
Analysis (SEAC) leading  to the granting  of authorisations for certain specific uses while other uses 
have been restricted following the restriction procedure (see Annex 5 – Case studies). 

Substances identified as endocrine disrupting substances of an equivalent level of concern to CMRs or 
PBT/vPvBs  include  the  phthalate  esters  DEHP,  DIBP,  DBP  and  BBP  (see  Annex  5B,  DEHP  case 
study). In fact, regulatory action on DEHP and other phthalates started in relation to the reproductive 
toxicity of the substances before ED-specific provisions were in place. The additional inclusion of a 
concern  for  endocrine  disrupting  effects  on  human  health  in  the  SVHC  list  did  not  directly  affect 
REACH authorisation and restriction procedures since they are based on the same effects that led to 
the inclusion due to toxicity for reproduction. However, it triggered additional risk provisions for risk 
assessment  (Chemical  Safety  Report)  and  risk  communication  (Safety  Data  Sheets)  and  required 
specific consideration of endocrine effects in reviews of authorisation. DEHP was also identified as an 
SVHC for endocrine effects on the environment and was added to the Candidate list for authorisation 
under REACH which also leads to an obligation to obtain authorisations in other sectors (food contact 
materials, medical devices). It also prompted the re-designation of DEHP from a Priority Substance to 
a Priority Hazardous Substance under the Water Framework Directive which requires that emissions 
be phased out. 

Other substances identified as SVHCs for the environment due to endocrine disrupting properties and 
placed on the REACH Candidate list include a number of alkylphenols and alkyl phenol ethoxylates. 
One of these, nonylphenol (NP), is an intermediate in the production of various derivatives including 
nonylphenol ethoxylates (NPnEOs) which were used as surfactants and emulsifiers in many different 
applications  including  detergents  with  consequent  widespread  emissions  to  the  aquatic  environment 
(see Annex 5C, NP case study). They have been progressively restricted over many years due to risks 
to  the  aquatic  environment,  firstly  via  the  1992  PARCOM62  convention  and  then  through  REACH 
restrictions together with setting of Environmental Quality Standards (EQSs) and actions taken under 
the  WFD.  NP  and  NPnEOs  were  identified  as  SVHCs  of  equivalent  concern  under  REACH  due  to 
endocrine disrupting effects on the environment in 2012 and 2013 respectively and further restrictions 
were  introduced  in  2016.  They  are  widely  restricted  in  the  EU,  with  a  few  speciality  biomedical 
applications  currently  subject  to  the  authorisation  requirements  after  NPnEOs  were  placed  on  the 
Authorisation List (Annex XIV) of REACH. In recent years increasing scientific knowledge has led to 
updates  of  predicted  no  effect  concentrations  (PNEC)  and  EQS  values  for  the  aquatic  environment. 
With  respect  to  human  health  concerns,  NP  was  classified  as  a  category  2  reproductive  toxicant  in 
2001 and consequent restrictions included the addition to the list of prohibited substances in cosmetic 
products. The closely related octylphenol and their ethoxylates were also identified as SVHCs due to 
endocrine  disrupting  effects  on  the  environment  in  2011  and  2012,  respectively,  and  are  similarly 
subject to authorisation requirements. 

62Convention for the prevention of marine pollution from land-based sources (Paris Convention) PARCOM 
Recommendation 92/8 on nonylphenol ethoxylates. https://www.ospar.org/convention/agreements/page13 

71 

 
 
                                                      
 
Box 5.5: Stakeholder views on effectiveness of REACH Regulation as regards EDs* 

Of the stakeholders expressing an opinion on the effectiveness of REACH, there is a roughly even 
split between those that consider the regulation is effective in protecting human health and those 
that do not when considering consumers (57 agree, 62 disagree, and 17 neither agree nor disagree) 
or  workers  (56  agree,  59  disagree,  and  18  neither  agree  nor  disagree).  A  smaller  proportion  of 
respondents  consider  that  the  regulation  is  effective  in  protecting  citizens  exposed  via  the 
environment  (46  agree, 63 disagree, and 26 neither agree nor disagree) or wildlife (43 agree, 67 
disagree, and 23 neither agree nor disagree).  

The  proportion  of  each  stakeholder  group  answering  that  the  Regulation  is  not  effective  is 
presented in the graph below: 

Answers are given as a percentage of respondents from each stakeholder group. For more details see Annex 2. 

Regarding human health and environmental protection, some respondents (from academia, or civil 
society organisation) declared that the risk-based control of ED substances in REACH may lead to 
insufficient  protection,  while  others  (representing  Industry)  stated  that  there  is  a  high  level  of 
protection of consumers, workers, citizens and the environment. 

Motivations for respondent’s replies include the following: 

 

 

 

 

the process to identify substances as EDs is too slow, with only 16 substances identified so far 
as ED. Application of a grouping approach could be a way to speed up the process. 
some  respondents  suggested  to  extend  the  simplified  restriction  procedure  (art.68,  §2)  for 
CMR cat1A or 1B in consumer products to endocrine disruptors. 
there were some suggestions to remove the “equivalent level of concern” (ELoC) step so that 
the  new  horizontal  criteria  would  automatically  fulfil  Art.  57(f)  or  by  creating  an  additional 
category as Art.57(g). Another option could be to develop a guidance on the interpretation of 
‘ELoC’. 
inclusion on the Candidate List should be automatic for substances with known ED properties 
(whether  classified  or  not).  SVHCs  not  registered  under  REACH  should  immediately  be 
moved to Annex XIV and if no authorisation applications are made before the sunset date, all 
uses should be automatically restricted (i.e. the substance should be included in Annex XVII).  

72 

0%10%20%30%40%50%60%70%80%90%100%protection ofconsumersprotection ofworkersprotection ofcitizensprotection ofwildlifeimprovement ofthe internal marketenhancement ofcompetitivenessand innovationpromotion ofalternatives toanimal testingOtherBusiness associationCompany/business organisationTrade unionCivil society organisationsAcademic/research institution 
 
 
 
 
 
*Respondents  to  all  three  surveys  (citizens,  stakeholder  and  SME  surveys)  were  self-selected  and  thus  not 
necessarily representative of the full range of views of these groups. 

Apart  from  SVHC  identification  and  authorisation,  REACH  contains  the  restriction  procedure  as  a 
powerful tool for imposing risk management measures including the complete ban of a substance.  

A restriction can be put in place if there is an unacceptable risk to human health or the environment 
that  arises  from  the  manufacturing,  use  or  placing  on  the  market  of  a  substance.  Examples  of 
restricted substances with confirmed or suspected endocrine disrupting properties are multiple organo-
tin  compounds,  the  mentioned  octylphenol,  nonylphenol  as  well  as  their  ethoxylates,  phthalates, 
perfluorooctanoic  acid  and  related  substances,  or  substances  that  are  now  regulated  under  the 
Regulation (EU) 2019/1021 (e.g. decabromo diphenylether). However, only octylphenol, nonylphenol 
and their ethoxylates are restricted due to their ED properties. 

In  the  targeted  stakeholder  survey  comparing  BPR,  PPPR  and  REACH,  the  large  majority  of 
respondents  with  an  opinion  stated  that  REACH  is  the  regulation  with  the  lowest  likelihood  of 
identifying  a  substance  as  an  endocrine  disruptor.  This  view  was  mainly  coming  from  respondents 
from  public  authorities,  as  well  as  respondents  from  academia  and  civil  society  organisations.  The 
main two reasons for this ranking were: 1) the few data requirements for low tonnage substances, and 
2) the lack of specific information requirements for EDs. Testing for endocrine properties is triggered 
based on observations coming from repeat dose and reproductive/developmental testing, and chronic 
tests in aquatic organisms, however, these tests may not be available since REACH applies a tiered 
approach  for  information  requirements,  based  on  production  tonnage.  Thus  such  tests  would  not  be 
required for low tonnage substances, limiting the possibility to detect toxicological effects (this aspect 
is  not  ED  specific).  In  contrast,  investigation  of  endocrine  disrupting  properties  is  mandatory  under 
the BPR and PPPR, irrespective of tonnage level. 

Some respondents also mentioned that the REACH process could be strengthened by making the BP 
and PPP ED-identification criteria applicable and formally used by the REACH-SVHC process. This 
option  would  be  in  line  with  the  Commission’s  aim  to  develop  a  horizontal  approach  to  ED 
identification. However, it should be noted that the BP and PPP criteria were developed specifically 
for  these  two  regulations  and  it  needs  to  be  examined  whether  they  can  be  applied  directly  for 
REACH  processes.  It  was  also  mentioned  that  the  additional  requirement  within  REACH  to 
demonstrate an equivalent level of concern as for CMRs or PBTs/vPvBs when identifying an ED as a 
substance of very high concern (SVHC) also decreases the likelihood of an identification. 

A point was also made in favour of the creation of a European mechanism to enable the European and 
national agencies, to carry out independent studies on potential EDs. It was suggested that the work 
should be financed by an increase in the fees charged by the agencies to companies. 

  Other sector-specific and product-specific legislation 

5.4
Many pieces of sector-specific and product-specific legislation have provisions to address risks posed 
by hazardous substances, but do not require the necessary toxicity data to be generated to allow the 
identification  of  the  hazard.  Substances  used  in  some  sectorial  legislation,  such  as  the  Toy  Safety 
Directive,  Detergents  Regulation,  Fertilisers  Regulation,  Food  Contact  Materials  Regulation,  the 
Cosmetic  Products  Regulation  and  the  Medical  Devices  Regulation,  are  required  to  be  registered 
under  REACH  (unless  produced/imported  at  <1  tonne/annum).  Some  pieces  of  sectorial  legislation 
rely  primarily  on  REACH  for  ED  identification,  others  such  as  food  contact  materials,  cosmetic 

73 

 
 
 
 
products and food additives have further requirements for products or sectors they regulate but these 
do not, as yet, specifically address endocrine disruption. 

It is important to bear in mind that many substances may have more than one hazardous property and 
indeed  this  is  often  the  case  with  EDs  since  the  adverse  effect  associated  to  the  endocrine  mode  of 
action  might  also  be  classified  as  e.g.  a  carcinogen,  mutagen  or  reproductive  toxicant  (CMR).  EDs 
might  also  be  persistent,  bioaccumulative  and  toxic  or  very  persistent  and  very  bioaccumulative 
(PBTs/vPvBs).  For  substances  where  the  adverse  effect  caused  through  disruption  of  the  endocrine 
system has already been identified and appropriate risk management measures have been applied, the 
effective measures to minimise exposure may already be in place and identification of a substance as 
an  ED  would  not  bring  any  additional  measures.  However,  this  may  not  always  be  the  case  and 
knowledge that a substance is an ED can increase the level of concern, which may lead to stricter risk 
management measures being applied. 

In  product  or  sector  specific  legislation  with  no  ED-specific  provisions,  there  are  possibilities  to 
evaluate the risks and apply appropriate risk management measures on a case-by-case basis. This may 
occur  when  endocrine  disrupting  properties  of  a  substance  become  known  through  other  regulatory 
processes e.g. under REACH or through publication of scientific papers. 

When  asked  for  which  sectors  they  think  ED  identification  should  be  more  specifically  introduced 
some stakeholders referred to the WFD (any Priority Substance with known ED properties should be 
identified  as  a  Priority  Hazardous  Substance),  the  Detergents  Regulation  (identification  of  EDs 
especially for the environment should be emphasized), and the toy safety directive. 

Several  respondents  also  proposed  to  adopt  a  “one  substance-one  assessment”  approach,  which 
would,  in  their  opinion,  increase  the  effectiveness  of  regulatory  procedures  while  avoiding 
discrepancies in ED identification. Under this scenario, there would be no need for specific provisions 
in each of the legislative pieces, but rather a reference could be made to an overarching regulation like 
REACH which already has provisions allowing for ED identification. 

Pieces  of  legislation  where  some  stakeholders  consider  that  risk  management  measures  for  EDs 
should  be  more  explicitly  described  include  occupational  safety  and  health  Regulations,  indoor  air 
pollution, industrial emissions, waste and water Regulations. Several stakeholders suggested that ED 
identification  under  one  regulation  should  automatically  trigger  risk  management  measures  for  the 
same substance under other regulations. 

When  asked  about  the  impact  on  human  and  environmental  health  of  either  hazard-based  or  risk-
based approaches63 to decision making, both were viewed positively by the majority of respondents in 
the  stakeholders  survey  with  slightly  more  support  for  risk-based  approaches.  However,  some 
differences  emerge  when  looking  at  specific  stakeholder  groups.  Representatives  from  industry 
(business  association  and  company/business  organisation)  have  a  marked  preference  for  risk-based 
decision making while civil society organisations favour a hazard-based approach. Similar responses 
were received with respect to both environment and human health.  

Water Framework Directive and Medical Devices Regulation 

63The terminology “hazard-based” and “risk-based” approaches is used in the context of consultation activities 
of this Fitness Check. The terms are equivalent to “generic risk” and “specific risk” approaches used elsewhere 
in the document. 

74 

 
 
 
                                                      
The provisions on EDs in the Water Framework Directive and the Medical Devices Regulation refer 
to  the  steps  to  follow  once  a  substance  is  identified  as  an  ED  but  there  are  no  mechanisms  within 
either piece  of legislation  for ED identification. The Medical  Devices Regulation  relies on  REACH 
and on the BPR for ED identification. However, there is no provision that requires all substances used 
in  medical  devices  to  be  evaluated  under  REACH  for  ED  properties.  Only  if  the  medical  device 
manufacturer  is  also  considered  a  manufacturer,  an  importer  or  a  downstream  user  under  REACH, 
would  the  related  REACH  obligations  apply  (i.e.  a  chemical  safety  assessment).  The  Water 
Framework Directive (WFD) has also relied largely on REACH for ED identification. 

75 

 
 
Box  5.6:  Stakeholder  views  on  effectiveness  of  Medical  Devices  Regulation  and  WFD  as 
regards EDs* 

Regarding the Medical Devices Regulation: 

A large proportion of stakeholders who replied to the closed questions say they do not know about 
the effectiveness of the regulatory process of the Medical Devices Regulation. Of those expressing 
an  opinion,  more  respondents  disagree  than  agree  that  it  is  protecting  consumers,  protecting 
workers or enhancing competitiveness and innovation. 

The  proportion  of  each  stakeholder  group  answering  that  the  Regulation  is  not  effective  is 
presented in the graph below: 

Answers are given as a percentage of respondents from each stakeholder group. For more details see Annex 2. 

Reasons given in support of their views were as follows: 

 

 

 

 

regarding  human  health  protection,  some  respondents  (from  civil  society  organisations  and 
academic/research  institutions)  stated  that  while  the  Medical  Devices  Regulation  introduces 
new provisions with regard to EDs, the provisions are considered too weak to allow the proper 
identification of EDs, since the dependency on REACH (for data) hampers the effectiveness of 
the regulation and makes the horizontal approach for EDs critical.  
these respondents called for a systematic testing of the substances used in medical devices for 
possible ED concern. 
some stakeholders (from civil society organisations) considered that patients are still exposed 
to EDs via medical devices even if in many cases safer alternatives exist 
the effectiveness of the Medical Devices Regulation is limited by the possible exemptions.  

76 

0%10%20%30%40%50%60%70%80%90%100%protection ofconsumersprotection of workersimprovement of theinternal marketenhancement ofcompetitiveness andinnovationpromotion ofalternatives to animaltestingOtherBusiness associationCompany/business organisationTrade unionCivil society organisationsAcademic/research institutionPublic authority 
 
 
 
 
 
 
Regarding the Water Framework Directive: 

More respondents disagreed than agreed that the directive is effective in minimising the exposure 
of  citizens  (22  agree,  47  disagree,  and  12  neither  agree  nor  disagree)  or  wildlife  (27  agree,  47 
disagree,  and  12  neither  agree  nor  disagree)  to  endocrine  disruptors  via  the  environment. 
However, the numbers of “don’t knows” were relatively high. 

The  proportion  of  each  stakeholder  group  responding  that  the  Regulation  is  not  effective  is 
presented in the graph below: 

Answers are given as a percentage of respondents from each stakeholder group. For more details see Annex 2. 

Reasons given in support of their views were as follows: 

  WFD  is  ineffective  at  protecting  consumers  and  the  environment  from  exposure  to  EDs 
because of the lack of coordination between the WFD and upstream chemicals legislation.  
  Only a few EDs are monitored in surface waters, and it is difficult to update the list of priority 

substances. 

  WFD  does  not  succeed  to  apply  the  ‘polluter  pays’  principle.  While  companies  releasing 
chemicals  into  the  environment  have  virtually  no  obligations  regarding  ED  assessment,  the 
burden of monitoring and follow up action falls mostly on public authorities and taxpayers. 

*Respondents  to  all  three  surveys  (citizens,  stakeholder  and  SME  surveys)  were  self-selected  and  thus  not 
necessarily representative of the full range of views of these groups. 

Cosmetic Products Regulation (CPR) 

In the case of the Cosmetic Products Regulation (CPR), which does not have specific provisions for 
EDs, the environmental risks of endocrine disruptors are explicitly covered by REACH but the human 
health  assessments  are  dealt  with  under  the  CPR.  Under  the  CPR,  substances  classified  as 
carcinogens, mutagens and reproductive toxicants (CMRs) category 1A/1B or 2 are prohibited unless 
specific  derogations  are  applied  (see  Annex  4).  EDs  that  are  also  CMRs  would  fall  into  the  same 

77 

0%10%20%30%40%50%60%70%80%protection of citizensprotection of wildlifeOtherBusiness associationCompany/business organisationTrade unionCivil society organisationsAcademic/research institutionPublic authority 
 
 
 
 
 
category.  The  SCCS  also  proposes  to  follow  a  specific  risk  approach  for  identified  or  potential 
endocrine disruptors which might cause other types of adverse effects. The question still arises how to 
ensure  the  systematic  consideration  of  endocrine  disrupting  properties  in  cosmetic  ingredient 
assessments. Following the review of the CPR64 the Commission committed to establish a priority list 
of  potential  EDs  not  already  covered  by  bans  or  restrictions  in  the  CPR  for  their  subsequent  safety 
assessment. A priority list of 28 potential EDs in  cosmetic products was consolidated in early 2019 
based on input provided through a stakeholder consultation. The list was prioritised and 5 substances 
are  currently  under  risk  assessment  by  the  SCCS.  Due  to  the  animal  testing  ban  in  the  cosmetics 
sector, a specific issue arises concerning the identification of EDs (see Annex 4) and in particular the 
need to demonstrate the adverse effect for an ED, which currently requires in vivo testing. This raises 
a  fundamental  question  about  the  interpretation  of  the  IPCS/WHO  definition,  namely  whether  it  is 
strictly necessary to observe adverse effects in animals, or whether the likelihood of adversity can be 
extrapolated  from  effects  in  non-animal  methods.  However,  the  difficulty  to  conclude  on  adverse 
effects  due  to  the  animal  testing  ban  is  not  restricted  to  endocrine  disruption  but  is  also  relevant  to 
other endpoints (such as reproductive toxicity). Respondents to the stakeholder survey propose some 
possible solutions (see Box 5.7). 

64COM(2018) 739 

78 

 
 
 
                                                      
Box 5.7: Stakeholder views on effectiveness of the Cosmetic Products Regulation as regards EDs*,** 

For  cosmetic  products,  more  respondents  disagree  than  agree  that  the  regulation  with  respect  to  EDs  is 
protecting  consumer  health  (31  agree,  48  disagree,  and  23  neither  agree  nor  disagree)  or  worker  health 
(professional users) (24 agree, 49 disagree, and 28 neither agree nor disagree). 

The proportion of each stakeholder group answering that the regulation is not effective is presented in the 
graph below: 

  Some stakeholders (from public authorities, civil society organisations, academic/research institutions) 
mentioned that the SCCS is currently risk assessing EDs without taking all the uncertainties in relation 
to assessment of EDs into account (e.g. low dose effects, non-threshold issue, lack of knowledge, lack 
of  adequate  test  methods),  limiting  the  effectiveness  of  the  regulation.  Others  (mainly  from  business 
associations  and  companies/business  organisations)  think  that  the  fact  that  these  substances  can  be 
subject to restriction or prohibition is a conservative approach for consumer safety. 

  Some stakeholders (from civil society organisations) challenged the viewpoint that the data necessary 
for the SCCS to identify and assess possible endocrine disrupting effects are available. They report that 
five  of  the  parabens  that  were  banned  in  2014  were  so  because  industry  chose  not  to  support  the 
substances  (limited  or  no  data  were  submitted  by  industry  to  the  SCCS  which  therefore  could  not 
evaluate their risk to human health). 

  Some stakeholders (from public authorities, trade unions and civil society organisations) consider that 
the effectiveness of the CPR for EDs is decreased by the lack of automatic risk management measures 
(i.e. automatic ban of CMRs). 

  Many respondents (from public authorities, civil society organisations, academic/research institutions) 
acknowledge  that  the  ban  of  animal  testing  without  suitable  alternatives  with  equivalent  value  to 
identify ED makes it difficult to properly identify hazard related to ED. However, use of animal data 
for ED identification is possible for substances also assessed under REACH. 

  Some respondents (mainly from civil society organisations) stated that the  integration of all available 
information  (such  as  physicochemical  properties,  literature,  in  vitro,  in  silico  data)  in  a  weight  of 
evidence can be used to exclude the potential toxicity of a cosmetic ingredient through the endocrine 
related effects 

  Some  stakeholders  suggested  to  define  a  “potential  endocrine  activity”  as  a  way  to  address  the 

challenge raised by the ban of animal testing in the cosmetics sector. 

  Some stakeholders from civil society organisations and public authorities suggest that in the context of 
the  CPR,  the  precautionary  principle  should  be  applied  for  all  substances  suspected  to  be  endocrine 
disruptors in the absence of animal data, in order to increase the effectiveness of the regulation. 

  Some  stakeholders  mentioned  that  the  lack  of  clear  identification  of  the  presence/absence  of  EDs  in 

cosmetic products leads to consumer mistrust. 
79 

0%10%20%30%40%50%60%70%80%90%100%protection of consumersprotection of workersimprovement of theinternal marketenhancement ofcompetitiveness andinnovationpromotion ofalternatives to animaltestingOtherBusiness associationCompany/business organisationTrade unionCivil society organisationsAcademic/research institutionPublic authority 
 
 
 
 
*Answers are given as a percentage of respondents from each stakeholder group. For more details see Annex 2. 

**Respondents  to  all  three  surveys  (citizens,  stakeholder  and  SME  surveys)  were  self-selected  and  thus  not 
necessarily representative of the full range of views of these groups. 

Stakeholder  views  regarding  the  effectiveness  of  the  Cosmetic  Products  Regulation  reflect  the 
differences  in  risk  assessment  and  management  where  a  specific  risk  approach  is  advocated  by  the 
SCCS  compared  with  a  hazard-based  approach  under  the  Biocidal  Products  and  Plant  Protection 
Products Regulations, or REACH. This aspect is further analysed in Sections 4.3 and 4.4.   

Viewpoints  of  SMEs  and  citizens  have  also  been  gathered  regarding  the  effectiveness  of  EU 
legislation. 

In  general,  respondents  to  the  SME  survey  consider  the  regulatory  process  to  identify  and  control 
chemicals  with  endocrine  disrupting  properties  to  be  effective  in  protecting  people  (40-45  agree,  9 
disagree,  6-9  neither  agree  nor  disagree)  and  wildlife  (38  agree,  9  disagree,  11  neither  agree  nor 
disagree),  in  improving  the  functioning  of  the  internal  market,  and  enhancing  competitiveness  and 
innovation (30 agree, 10 disagree, 10 neither agree nor disagree). 

With regard to the views from the citizens, the majority of respondents (54% to 74%) consider that 
EU  laws  do  not  protect  them  at  all  or  only  to  a  small  extent  from  exposure  to  endocrine disruptors 
across  all  of  the  potential  exposure  sources  listed  in  the  survey.  The  four  exposure  sources  where 
respondents  consider  that  EU  laws  protect  them  the  least  are  personal  care  products,  food  contact 
materials,  clothing,  and  home  or  office  furnishings,  floors  and  paints.  Moreover,  when  respondents 
were  asked  which other sources of exposure to endocrine disruptors were of particular concern, the 
most often mentioned were pesticides, toys, as well as effects due to combined exposure to EDs. 

  Communication  

5.5
Current mechanisms are in place to inform consumers and recipients of articles in general about the 
presence  of  substances  of  very  high  concern  (SVHCs)  with  ED  properties  (REACH  Article  33). 
Furthermore, producers and importers of articles containing SVHCs must notify ECHA under certain 
conditions (e.g. if the SVHC is intended to be released from the product (REACH Article 7). Safety 
Data Sheets (REACH Annex II) are required to include information on whether a substance has been 
identified as an endocrine disruptor or whether such a substance is present in a mixture. An update of 
the provisions for Safety Data Sheets that includes further obligations to report on EDs was recently 
agreed  in  the  Commission’s  REACH  Committee  and  will  apply  from  1  January  2021.  Similarly, 
under the Biocidal Products Regulation, safety data sheets for active substances and biocidal products 
shall be prepared and made available in accordance with REACH (Art 70). Moreover, articles treated 
with a biocidal product shall display a list of the active substances on the label (Art 58).   

The respondents to the citizens’ survey feel they lack information on the presence of EDs in products, 
or that the information is difficult to understand. Moreover, the respondents called for more and better 
information on EU activities regarding EDs. The European Commission has recently launched a web 
portal65 providing a single point of access to all EC activities related to EDs. 

65https://ec.europa.eu/info/policies/endocrine-disruptors_en 

80 

 
 
 
 
                                                      
  Monitoring data 

5.6
Environmental and human monitoring data are useful for providing evidence on the effectiveness of a 
risk-reduction measure, as well as providing alerts to rising levels of substances of potential concern 
and  in  understanding  actual  human  and  environmental  exposures  including  combined  exposures  to 
mixtures  of  substances.  EU  Member  States  monitor  several  EDs  in  surface  waters  under  the  WFD, 
either because Environmental Quality Standards already exist or to determine whether the substances 
pose a risk and should be regulated. The European Human Biomonitoring Initiative (HBM4EU66), is a 
5-year  project  which  was  launched  in  2017  to  respond  to  the  need  for  harmonised  information  at 
European level concerning human exposure to chemicals in order to support reliable risk assessment 
and management. HBM4EU is a joint effort of 30 countries, the European Environment Agency and 
the  European  Commission,  co-funded  under  Horizon  2020.  The  initiative  is  coordinating  and 
advancing human biomonitoring in Europe. HBM4EU is generating evidence of the actual exposure 
of citizens to chemicals and the possible health effects in order to support policymaking. A number of 
EDs such as bisphenols, phthalates and flame retardants have been prioritised under the programme, 
and data are being made available via the Information Platform for Chemical Monitoring67. A similar 
initiative, albeit smaller in scale, for terrestrial and aquatic wildlife is the LIFE APEX project68 which 
focuses  on  chemical  monitoring  in  apex  predators  and  their  prey.  A  more  regular  screening  of 
'unknowns' (i.e. sampling and testing designed to detect unsuspected hazardous chemicals) in humans 
and the environment is also missing. 

Such  monitoring  was  done  in  the  US  after  the  ban  on  PBDEs  at  the  beginning  of  2004.  Blood 
measurements  in  pregnant  women  (111)  showed  a  decline  in  the  PBDE  concentrations  between 
2008/09 and 2011/12, but appeared to plateau between 2011/12 and 2014 (possibly due to persistence 
and bioaccumulation, from dust and food) (Parry 2018). Another study on 334 children, with repeated 
sample collection from birth to 9 years of age over a 15-year period, found a significant decrease of 
PBDEs between 1998 and 2013 (Cowell, 2019). 

However,  an  aspect  which  is  not  adequately  considered  with  regard  to  the  regulation  of  EDs  is 
combined  exposure,  although  this  issue  is  not  unique  to  EDs.  Provisions  for  the  assessment  of 
cumulative  exposure/effects  exist  in  the  Maximum  Residue  Levels  of  Pesticides,  the  Biocidal 
Products and Plant Protection Products Regulations. Two retrospective cumulative risk assessments of 
dietary exposure to pesticide residues have been recently carried out by EFSA: one considering two 
chronic effects on the thyroid system and another looking at two acute effects on the nervous system 
(EFSA, 2020a, b). In both cases, it was concluded that cumulative exposure to pesticide residues did 
not  exceed  the  threshold  for  regulatory  consideration  established  by  risk  managers  on  the  basis  of 
individual  substance  assessments.  Under  REACH,  four  phthalates  (DEHP,  DBP,  BBP  and  DIBP) 
have recently been further restricted based on combined exposure estimates, with diet indicated as a 
signficant source of exposure to DEHP. While EFSA concluded that there is no risk from the three of 
these phthalates that are authorised in Food Contact Materials, consequential risk management takes 
into account both combined exposure to the phthalates with the same mode of action and cumulative 
exposure from other sources. In water legislation, the application of effect-based methods (European 
Commission, 2014) is a promising development. 

66https://www.hbm4eu.eu/about-hbm4eu/ 
67IPCHEM: https://ipchem.jrc.ec.europa.eu/RDSIdiscovery/ipchem/index.html  
68https://lifeapex.eu/ 

81 

 
 
                                                      
Considering  the  possible  non-monotonic  dose-response  of  EDs,  it  is  difficult  to  predict  combined 
effects  from  exposure  to  multiple  EDs  using  standard  additivity-based  approaches  (which  assume 
monotonic  behaviour)  using  information  on  individual  chemicals,  and  the  potential  for  combined 
effects adds to the overall uncertainties of a risk assessment (Bopp et al., 2019; Munn and Goumenou, 
2013b). 

Box  5.8:  Stakeholder  views  on  aggregate  exposure  and  combined  effects  of  endocrine 
disruptors* 

  Amongst the respondents giving an opinion, about 60% (145-160 of 183 respondents) disagree 
that  the  current  regulatory  framework  protects  humans  or  wildlife  from  the  risks  associated 
with  the  aggregate  exposure  to  one  substance  with  endocrine  disrupting  properties  from  all 
exposure sources. Similar results were obtained regarding protection to combined exposure to 
different  substances  with  endocrine  disrupting  properties.  Similar  comments  were  made  by 
respondents to the citizens survey. 

  Several stakeholders (mainly from public authorities) highlighted the fact that in order to take 
into  account  aggregate  exposure  and  combined  effects 
for  EDs,  a  horizontal 
definition/identification would be needed. Cross-agency initiatives should be developed to deal 
with aggregate exposure and combined effects. 

  Some  stakeholders  mentioned  that  aggregate  exposure  and  combined  effects  are  particularly 

relevant for EDs because of their no/low threshold. 

  Some stakeholders mentioned that several pieces of legislation consider aggregate exposure to 

a certain extent (such as REACH), however it is never considered across regulations 

  Some  stakeholders  suggested  that  the  aggregate  exposure  assessment  methodology  under 

REACH could be further developed to cover all sectorial uses.  

  Several  respondents  (from  civil  society  organisations)  suggested  that  where  health  concerns 
are  raised  in  one  sector,  it  should  automatically  trigger  risk  evaluation  across  legislative 
sectors to fully assess the impact of combined exposure. 

  Some stakeholders stated that combined effects are relevant only if substances have the same 

adverse outcome pathway. 

*Respondents  to  all  three  surveys  (citizens,  stakeholder  and  SME  surveys)  were  self-selected  and  thus  not 
necessarily representative of the full range of views of these groups. 

Although only a few substances have been formally identified and controlled due to their endocrine 
disrupting activity, many substances with endocrine disrupting properties have already been identified 
due  to  other  hazardous  properties  which  may  or  may  not  be  related  to  endocrine  disruption  (e.g. 
reproductive 
toxic  (PBT)/very  persistent,  very 
bioaccumulative (vPvB) properties). Consequently, regulatory measures to reduce exposures to some 
of these substances have already been taken and environmental monitoring and human biomonitoring 
have been used to follow the trends in exposure to such substances over time.  

toxicity  or  persistent,  bioaccumulative  and 

The case study on DEHP (Annex 5B, DEHP case study) illustrates through human biomonitoring data 
(levels of phthalate metabolites in the urine) how the successively increased restrictions on DEHP and 
other  low  molecular  weight  phthalates  over  time  have  been  successful  in  reducing  exposure  of  the 
human  population  in  the  EU.  With  respect  to  nonylphenol  (Annex  5C,  NP  case  study)  there  is 
evidence  of  substantial  decreases  in  aquatic  concentrations  in  EU  wastewater,  surface  waters  and 
biota  in  the  last  two  decades.  For  instance,  concentrations  in  fish  (bream,  muscle  tissue)  caught  in 
Germany diminished by 67% between 1995 and 2001. However, reduced concentrations of NP in the 

82 

 
 
 
 
 
aquatic environment cannot be linked to changes in estrogenic activity of water bodies because this is 
mainly driven by more potent natural and synthetic estrogens. 

One concern is that of ‘regrettable substitution’ where the restricted substance is replaced by another 
substance  able  to  provide  a  comparable  technological  function  but  which  might  also  be  similarly 
hazardous, although the substance is not so well tested so these properties are not known at the time of 
the  replacement.  This  could  reduce  the  effectiveness  of  the  measures.  To  reduce  the  possibilities  of 
this occurring  there is  a  move towards group  assessments,  where substances  with similar  molecular 
structure, with similar properties or with similar functions are assessed together. This requires either 
the  generation  of  comparable  data  for  each  substance  in  the  group  or  the  use  of  ‘read  across’ 
approaches. Indeed, regulatory action on phthalates did follow a group approach whereby a group of 
low molecular weight phthalates (DEHP, DBP, DIBP and BBP) were assessed together. 

A number of Persistent Organic Pollutants (POPs) have endocrine disrupting properties and inclusion 
in the POPs Regulation defines requirements for reporting environmental release inventories (Article 
6),  environmental  monitoring  (Article  10)  and  production  volumes  (Article  12).  Release  should  be 
minimised or eliminated from all sources (Article 6) including waste (Article 7). Waste containing or 
contaminated  with  POPs  should  be  handled  to  ensure  no  release  or  recirculation  in  recycled/reused 
material flows. Recent reviews describing spatial and temporal trends of some of these substances in 
the  environment  provide  an  opportunity  to  evaluate  the  effectiveness  of  the  regulatory  measures  in 
relation to exposure reductions. One example looking at levels of flame retardants (PBDEs) in human 
breast  milk,  cord  blood  and  placentas  found  levels  of  PBDEs  in  North  America  were  substantially 
higher than those in many regions of Europe, Asia, Oceania or Africa. One possible explanation given 
for this was the higher use of flame retardants in furniture in North America (Tang and Zhai, 2017). 

  Human health and environmental impact evidence and indicators 

5.7
The trends in the main health and environmental impact parameters that are known, or suspected, to 
be  associated  with  exposures  to  endocrine  disrupting  substances  are  important  considerations  when 
examining  the  effectiveness  of  EU  chemicals  policy.  These  trends  include  upward  trends  in  the 
incidence rates of certain hormone-related cancers and reproductive diseases, decreasing fertility rates 
in females and males and decreasing sperm counts, and on the environmental side reduction in species 
diversity and eco-system health/resilience. However, caution needs to be exercised when using human 
health  and  environmental  adverse  effects  as  direct  and  reliable  indicators  of  chemicals  policy 
performance.  This  is  because  of  the  attribution  challenge:  many  of  the  observed  health  and 
environmental  adverse  effects  may  derive  from  multiple  causes  (life-style,  genetics,  habitat 
destruction/degradation,  etc.)  and  it  is  difficult  to  determine  to  what  extent  exposure  to  endocrine 
disrupting  substances  contributes  to  the  observed  adverse  effects69.  Statistical  approaches  exist  and 
have been applied in (eco)epidemiology with the aim of separating the contribution of (mixtures of) 
chemicals from other contributing or confounding factors (Gennings et al., 2018; Slama et al., 2017). 
Differences in study design and low reproducibility of findings, however, remain a major  challenge 
for use in a regulatory context. 

Complicating  things  further  is  the  fact  that  observable  adverse  effects  in  human  health  and  the 
environment  often  do  not  materialise  immediately  after  exposure.  For  example,  the  effects  of  early 
life  exposure  to  endocrine  disruptors  may  not  materialise  until  many  years  later.  Moreover,  the 

69SWD(2019) 199 

83 

 
 
                                                      
involvement of the endocrine system in the control of processes such as embryonic development and 
puberty means that young people are at higher risk regarding endocrine disruption.  

Indeed, developing organisms are extremely sensitive to perturbation by chemicals with hormone-like 
activity,  and  adverse  effects  may  be  most  pronounced  in  the  developing  organism  and  occur  at 
concentrations of the chemical that are far below levels that would be considered harmful in the adult. 
The  continued  maturation  of  key  endocrine  systems  during  childhood  and  adolescence,  make  these 
life periods also particularly sensitive to endocrine disruption, beyond foetal development  (Schug et 
al.,  2011).  Many  of  the  adverse  effects  on  development  in  late  pregnancy  and  early  childhood  are 
expressed  as  functional  deficits  in  organs  or  systems,  instead  of  overt  malformations  or  growth 
retardation (Schug et al., 2011). Evidence from many studies support the hypothesis of a relationship 
between  exposure  to  EDs  and  early  maturation  of  secondary  sexual  characteristics  (e.g.  precocious 
puberty) (Lee et al., 2019; Lucaccioni et al., 2020) or predisposition to breast cancer (occurring later 
in  life  after  exposure  during  puberty)  (Lucaccioni  et  al.,  2020).  Exposure  to  EDs  during  early 
development  have  also  been  associated  with  non-reproductive  effects  such  as  obesity  and  related 
diseases (Petrakis et al., 2017). It is important when considering these vulnerable groups to ensure that 
the sensitive life stages are covered by the methods used to investigate toxicity and endocrine modes 
of action.  

Box 5.9: Stakeholder views on protection of vulnerable groups*  

When  asked  whether  various  groups  of  the  population  are  sufficiently  protected  from  endocrine 
disruptors,  stakeholders  replied  that  the  level  of  protection  is  generally  insufficient  (ranging 
between 56% of respondents considering adults in general, to 66% for the unborn exposed during 
pregnancy).  Similar  views  were  shared  by  respondents  to  the  citizens  survey,  with  over  60%  of 
respondents considering that EU laws offer a low level of protection for one or more life stages, 
with  highest  concern  for  adolescents  (75%)  and  the  lowest  for  pregnant  women,  foetuses  and 
newborns (62% to 66%). 

However, it should be noted that viewpoints differed among stakeholder groups, with only 14% to 
30%  of  representatives  from  business  associations  and  companies/business  organisations  stating 
that the various sub-groups within the population are insufficiently protected.  

Stakeholders mentioned that: 

  Clear definitions of children and vulnerable groups are missing in most EU chemical laws and 
there was a perception of a lack of  consistency in treatment of vulnerable groups across EU 
legislation. 

  The current data requirements and available test methods do not adequately cover vulnerable 

groups. 

Suggestions were made to increase the protection of children by: 

  Adding the possibility in the Toy Safety Directive to set new concentration limits for harmful 

substances in toys intended for children above 3 years.  

  Applying the same risk management for EDs as for CMR substances, i.e. the automatic ban of 

EDs in toys. 

*Respondents  to  all  three  surveys  (citizens,  stakeholder  and  SME  surveys)  were  self-selected  and  thus  not 
necessarily representative of the full range of views of these groups. 

84 

 
 
 
 
 
A  few  attempts  have  been  made  to  estimate  the  costs  of  endocrine-related  diseases/disorders  in 
humans and the proportion that might be attributable to exposure to endocrine disrupting substances. 

Four  studies  published  in  2015  (Bellanger  et  al.,  2015;  Hauser  et  al.,  2015;  Legler  et  al.,  2015; 
Trasande et al., 2015) estimated the costs associated to the use of several endocrine disruptors for a 
subset of health effects to be hundreds of billion euros per year. Those studies subsequently received 
criticism from other scientists, claiming their aim would be to shape policy (Middelbeek and Veuger, 
2015).  Further  criticism  related  to  alleged  methodological  flaws  and  the  hypothesis  on  which  the 
studies  were  based  (Bolt,  2017;  Bond  and  Dietrich,  2017a,  b;  Middelbeek  and  Veuger,  2015).  The 
main problem with such studies is the attribution challenge (i.e. that EDs are responsible for causing 
several  diseases  for  a  certain  minimal  percent  factor  of  probability).  The  Commission  reviewed  the 
four  studies  when  carrying  out  an  impact  assessment  in  the  context  of  setting  criteria  for  endocrine 
disruptors under the BPR and PPPR70. Other studies have tried to estimate costs linked to effects of 
endocrine disruptors on male reproductive health (Olsson and al., 2014). 

Nevertheless, there are examples of non-approval of substances with endocrine disrupting properties 
resulting in significant benefits to human health and wildlife. For instance, the restriction of the use of 
the endocrine disruptor tributyltin (TBT, REACH Annex XVII, entry 20) as an antifoulant in marine 
paints has resulted in the recovery of mollusc populations in many ports and coastal areas in Europe71.  

5.8

  Market surveillance 

An aspect which could weaken the effectiveness of EU legislation is differences compared with laws 
in  non-EU  countries.  The  potential  import  of  substances  banned  in  the  EU  from  non-EU  countries 
raises the issue of EU market surveillance.  

The respondents to the stakeholder survey mentioned that some substances banned in the EU but still 
allowed  in  other  countries  can  still  be  found  in  products  imported  and  marketed  in  the  EU.  Such 
statements are supported by an enforcement project conducted by ECHA’s Forum, which is a network 
of  national  authorities  responsible  for  the  enforcement  of  REACH  as  well  as  the  CLP,  Biocidal 
Products  and  PIC  Regulation.  The  project  investigating  compliance  with  the  REACH  restriction  on 
phthalates in toys and child-care articles found that 19.7 % of the inspected toys and 3.6% of childcare 
articles  contained  one  of  the  phthalates  above  the  permitted  level.  Most  products  found  to  be  non-
compliant came from countries outside of the European Economic Area or were of unknown origin 
(Annex 5B, DEHP case study). 

Moreover,  these  substances  can  be  found  in  the  environment  (e.g.  water  bodies,  including  by 
transboundary  flow).  Regarding  the  residues  of  pesticides  found  in  imported  products,  some 
stakeholders  suggested  to  set  the  maximum  residue  levels  (as  a  general  principle)  at  the  level  of 
quantification for substances falling under the cut-off (exclusion) criteria. 

Respondents  to  the  stakeholders’  survey  consider  that  all  sectors  would  benefit  from  an  increased 
market  surveillance.  In  particular,  the  fields  of:  feed  and  food  (environmental  contaminants,  natural 
toxins, flavouring agents); water, including drinking water; industrial emissions; the General Product 
Safety Directive (GPSD); products in contact with vulnerable groups, and online sales were listed by 

70SWD(2016) 211 
71Non-REACH FC CuBA Study, p. 204 

85 

 
 
 
 
                                                      
stakeholders  as  those  where  market  surveillance  authorities  should  focus  their  activities.  However, 
this aspect is not specific to endocrine disruptors and it has been recognised that its implementation 
depends on the resources available in Member States72.  

5.9

  Functioning of the internal market, competitiveness and innovation 

Box  5.10:  Stakeholder  views  on  the  efficient  functioning  of  the  internal  market,  and 
enhancement of competitiveness and innovation* 

For Biocidal Products: 

  The possibility of derogation according to Art 5(2) makes it difficult to assess the functioning 
of  the  internal  market  since  derogation  conditions  may  be  met  in  some,  but  not  all  Member 
States. 

  Some comments suggested that the complexity of the regulation does not facilitate innovation 

and the uncertainties/moving goalposts were negatively impacting innovation. 

For Plant Protection Products: 

  Some  respondents  mentioned  that  the  costs  incurred  by  the  additional  studies  necessary  to 
comply  with  the  "data  sufficiency"  of  the  ED  criteria  inevitably  compromise  investment  in 
research on new substances and innovative products. 

  Substances withdrawn are not likely to be replaced easily. According to one respondent there 
are  two  reasons  for  this:  first,  the  development  of  new  active  ingredients  up  to  market 
introduction  takes  about  11  years  and  costs  over  €280  million.  Secondly,  the  pipeline  of 
products  waiting  for  approval  for  the  European  market  is  also  getting  emptier  due  to  rising 
Research and Development time and costs. 

For REACH: 

  The lack of coherent criteria to identify endocrine disruptors may  impede the functioning of 

the internal market and could reduce competitiveness and innovation. 

  The  risk-based  regulation  of  EDs  under  REACH  provides  a  more  nuanced  approach 
accelerating the potential for innovations and more rapid substitution of ‘old’ substances with 
new better alternatives, while still ensuring protection of human health and the environment. 
  The  fact  that  non-EU  countries  can  still  use  substances  restricted/banned  in  EU  is  a 

competitive disadvantage for the European industry 

  The additional requirements to understand mode of action and the link with the adverse effects 
mean additional resource and cost requirements compared to non-EU competitors which can 
undermine competitiveness of EU producers. 

  The introduction of the REACH Regulation has resulted in a notable reduction in the number 
of  chemicals  used  on  the  European  market  as  manufacturers  must  balance  registration  costs 
against  possible  revenues,  while  also  taking  into  account  requirements  on  substance 
authorisation and restrictions. 

*Respondents  to  all  three  surveys  (citizens,  stakeholder  and  SME  surveys)  were  self-selected  and  thus  not 
necessarily representative of the full range of views of these groups. 

72SWD(2019) 199 

86 

 
 
 
 
 
                                                      
 
 
 
 
 
87 

 
 
 
 
 
6  EFFICIENCY 

 

 

Inefficiencies  in  the  assessment  and  management  of  endocrine  disruptors  can  result  from 
situations where a given substance falls under multiple pieces of legislation  and  thus within the 
mandate of multiple agencies and expert groups.  
Inefficiencies may also result from the absence of a common interpretation of certain regulatory 
provisions, such as “equivalent level of concern” under REACH. 

  EU  agencies  are  stepping  up  their  efforts  to  coordinate  assessment  work.  However,  additional 
efficiencies could be obtained by developing further a horizontal approach to EDs, including an 
increased use of new approach methodologies and grouping approaches. 

  The need to carry out testing and assessment for additional ED-related effects for a larger number 
of chemicals will inevitably lead to increased workload and costs. Some industry stakeholders are 
concerned  that  this  will  put  economic  operators  in  the  EU  at  a  competitive  disadvantage,  while 
some public authority stakeholders are concerned that this will result in delays to other areas of 
regulatory assessment work.  

  The  costs  and  benefits  for  human  health  and  the  environment  resulting  from  regulatory 
requirements to assess and risk manage chemicals, including endocrine disruptors, are difficult to 
quantify  and  compare.  There  is  a  need  to  further  develop  and  harmonise  risk-benefit 
methodologies, such as socioeconomic analysis. 
It was difficult to perform conclusive economic assessments on the possible impacts of regulatory 
interventions  on  trade.  This  is  partly  because  there  is  a  lack  of  trade  flow  data  at  the  level  of 
specific chemicals and the commodities containing these chemicals, as well as data on the market 
share  of  a  chemical  in  a  given  commodity.  Two  case  studies  illustrate  the  methodological 
challenges involved. 

 

Q4.  To  what  extent  has  EU  legislation  been  efficient  in  identifying  EDs  and  managing  risks 
related  to  their  exposure  across  different  legal  frameworks,  ensuring  the  protection  of  human 
health and the environment? 

There is evidence that a lack of coherence across regulatory sectors has had an impact on efficiency. 
This is particularly the case when multiple regulatory assessment and management procedures have 
focused on the same substances. Examples are given in the case studies (Annex 5). 

In  other  cases,  a  lack  of  efficiency  can  be  attributed  to  differences  in  the  interpretation  of  terms  in 
legislation. For example, under REACH, different views of Member States in ECHA’s Member State 
Committee (MSC) on the interpretation of 'equivalent level of concern' (Art. 57(f)) has resulted in a 
number of cases73 where the MSC could not reach unanimity on the identification of a substances as 
substance of very high concern, meaning that the decision had to be referred to the Commission via its 
REACH Committee (EC 2018a, part 1/7).  

The targeted stakeholder survey revealed a range of opinions on the efficiency of current regulatory 
procedures  for  assessing  and  managing  EDs  (see  Box  6.1).  A  slight  majority  of  respondents  (53%) 
thought  that  the  regulatory  framework  is  not  flexible  enough  to  take  into  account  new  scientific 
information and methods in the assessment of endocrine disrupting properties. Some commented on 
the need to give more weight in the evaluation process to non-standard sources of information (e.g. 

73As of May 2020, this applied to nine substances for different hazard endpoints, out of which seven related to 
EDs.  

88 

 
 
 
 
                                                      
non-guideline  methods, scientific literature findings). Others argued that the substance-by-substance 
approach is hampering the assessment process, which would be more efficient if grouping approaches 
were  more  widely  implemented.  Several  respondents  referred  to  the  time  lag  between  hazard 
identification and risk management, as well as perceived inefficiencies resulting from the time taken 
to officially adopt test methods, to update standard information requirements, or to update guidance 
documents.  

The costs and benefits for human health and the environment resulting from regulatory requirements 
to  assess  and  risk  manage  chemicals,  including  endocrine  disruptors,  are  difficult  to  quantify  and 
compare.  Regulatory  decision  making  requires  that  besides  impacts  on  human  health  and 
environment, economic and social impacts are assessed and considered. This is to provide regulation 
at minimum  cost but with maximum benefits to citizens, businesses and workers, as outlined in the 
Commission Better Regulation guidelines74. Costs of regulatory testing are discussed in Section 5.1. 

REACH  incorporates  these  principles  by  requiring  a  socioeconomic  analysis  for  applications  for 
authorisations  as  well  as  for  restriction  proposals.  Socioeconomic  analysis  is  a  tool  to  provide 
decision-makers with the necessary evidence and analysis on the socioeconomic impacts of different 
options  for  how  to  regulate  chemicals.  The  REACH  authorisation  procedure  requires  applicants  to 
submit  a  socio-economic  analysis  (ECHA,  2011).  The  ECHA  Committee  for  Socio-economic 
Analysis  (SEAC),  which  consists  of  experts  nominated  by  Member  States,  scrutinises  the 
socioeconomic  analysis  carried  out  in  the  authorisation  and  restriction  processes.  Stakeholder 
organisations  participate  in  SEAC  meetings  as  observers.  Some  stakeholders  have  claimed  that  the 
socioeconomic  analysis  for  authorisations  does  not  yield  satisfying  results  and  has  methodological 
limitations,  such  as  the  choice  of  discounting  rate  (Chemsec,  2019)75.  However,  the  socioeconomic 
analyses  applied  in  regulatory  processes  use  sensitivity  analyses  to  assess  the  impact  of  different 
discount rates. These sensitivity analyses have shown that use of lower discount rates would not have 
resulted in a different policy choice for any of the REACH restrictions or authorisations reviewed. 

In  view  of  the  challenge  of  conducting  cost-benefit  analyses,  one  recommendation  voiced  in  the 
stakeholder survey was that the EU should establish a population-based monitoring scheme to assess 
the long-term benefits of regulatory action. 

In  the  targeted  stakeholder  survey,  88%  of  respondents  (53  out  of  60)  representing  companies 
reported  an  increase  in  costs  related  to  compliance  with  regulatory  requirements  for  EDs  (Targeted 
Stakeholder Survey). The additional costs were most often (21 out of 68 respondents) attributed to the 
provision  of  test  data  on  endocrine  disrupting  properties.  Costs  related  to  substitution  efforts  were 
reported  by  19  out  of  65  respondents.  According  to  some  stakeholders,  such  efforts  have  been 
hampered by a lack of voluntary (non-regulatory) incentives, as  well as lack  of expertise,  tools and 
guidance  for  avoiding  regrettable  substitutions  (Ministère  de  la  Transition  Ecilogique  et  Solidaire, 
2019).  Other  costs  reported  by  stakeholders  were  related  to  the  development  of  new  testing 
methodologies and the regulatory reporting of ED properties. According to one industry stakeholder, 

74https://ec.europa.eu/info/law/law-making-process/planning-and-proposing-law/better-regulation-why-and-
how_en 
75The above-mentioned Chemsec report was presented at the 42nd meeting of SEAC. According to the minutes 
“Different views by members were expressed, some technical inaccuracies were noted. It was observed the aim 
of the document was to spur a political discussion.”: https://echa.europa.eu/about-us/who-we-are/committee-for-
socio-economic-analysis/meetings-of-the-seac/2019 

89 

 
 
                                                      
the lack of a globally consistent approach to assessment can lead to additional costs exceeding 10%. 
In general, however, most respondents did not specify the origin or magnitude of additional costs.  

In  the  SME  survey,  an  increase  in  total  operating  costs  was  reported  by  25  out  of  70  respondents, 
whereas 12 respondents reported no effect on operating costs. For the remaining 33 respondents, this 
question was either not applicable (30) or no answer was provided (3). Costs were attributed to: a) the 
replacement of substances (21 respondents); b) the preparation of registration or authorisation dossiers 
(14 respondents); c) the provision of test data (14 respondents); and d) the development of new testing 
methodologies (13 respondents). 

Stakeholder  opinions  on  whether  the  additional  costs  are  justified  varied.  Governmental  and  civil 
society  organisations  typically  considered  the  costs  justified,  in  the  overall  interest  of  public  health 
and environmental protection. Conversely, industry organisations and associations expressed concerns 
that  the  hazard-based  management  of  chemicals  results  in  a  competitive  disadvantage  for  EU 
operators, which is unjustified in exposure scenarios where the substance poses a low risk.   

In the SME survey, the additional costs were considered justified and proportionate for the benefits 
obtained  by  23  respondents,  not  at  all  justified  or  proportionate  by  8  respondents,  while  38  did  not 
know. 

Overall,  stakeholders who expressed an opinion considered the impacts of regulatory provisions for 
EDs  on  their  sectors  to  be  negative  (Targeted  Stakeholder  Survey).  Among  the  regulators,  80%  of 
respondents  (51  out  of  64)  reported  that  assessing  substances  for  endocrine  disrupting  properties 
resulted  in  a  delay  in  their  assessment  work  in  other  areas  of  human  health  or  environmental 
protection.  

In  the  SME  survey,  impact  of  the  provisions  for  endocrine  disruptors  on  innovation,  productivity, 
profitability  and  international  trade  within  their  sectors  was  perceived  as  negative  by  a  minority  of 
respondents (between 1 to 6) while another minority (7 to 10 respondents) considered the impact as 
positive.  

In the public survey, 26% of the 474 respondents considered that the costs of EU laws on endocrine 
disruptors are fully proportionate for the benefits accrued, 18% to a moderate extent, 15% to a small 
extent only, and 11% not at all. Thirty percent replied that they do not know. In addition, there was a 
general  perception  that  slightly  higher  costs  are  borne  by  the  agricultural  and  industrial  sectors 
compared with costs to citizens or ethical costs. 

In  principle,  differences  in  regulatory  assessment  and  management  procedures  between  the  EU  and 
non-EU countries could have (positive or negative) impacts on trade. However, it is very difficult to 
predict such impacts. Retrospective assessments using economic methodology can analyse trade flows 
before  and  after  regulatory  interventions,  but  the  results  must  be  interpreted  with  caution,  as 
illustrated by two case studies carried out by the JRC (see Box 6.2 and Canzian et al., 2020).  

90 

 
 
 
 
 
 
Box 6.1: Stakeholder views related to efficiency* 

  The  categorisation  of  EDs  including  a  suspected  category  would  increase  efficiencies  in 

assessment and risk management and would also stimulate substitution efforts.  

  Concerns  from  industry  that  a  hazard-based  approach  to  risk  management  could  result  in 
substances  posing  low  risk  being  removed  unnecessarily  from  the  market  as  well  as  regrettable 
substitutions. 

  Concerns  from  an  industry  association  that  lack  of  coherence  between  the  BPR  and  REACH 
regarding co-formulants is placing a disproportionate cost burden on industry and authorities. 
  Under  REACH,  the  need  to  prove  EDs  are  substances  that  give  rise  to  an  equivalent  level  of 
concern as CMRs to identify them as Substances of Very High Concern (SVHC) is inefficient. 
  The perception that the listing, at different points in time, of multiple properties of concern (e.g. 
reproductive  effects  and  endocrine  disruption)  for  the  same  substance  (e.g.  DEHP)  on  the 
REACH Candidate List is inefficient. 

  Concerns from civil society organisations that lack of coherence across regulatory sectors results 
in animal tests being performed unnecessarily, with slight variations in the endpoints included.  
  Differences in how endocrine disruptors are regulated in the EU compared with non-EU countries 
can result in a competitive disadvantage. An industry association gave the example of isophorone, 
with ECHA and US EPA having different data requirements. 

  A non-EU business association considered that EU regulations are more cost-intensive than other 

regions.  

  Concerns from governmental and civil society organisations about the time taken for regulatory 
action from ED identification to risk management, with examples from BPR, PPR and REACH. 
  Concerns from industry that financial losses could result from “stigmatisation” of substances with 

endocrine activity (Mode of Action). 

  Concerns  from  an  industry  association  that  restricting  the  number  of  biocidal  active  substances 
according  to  hazard-based  criteria  could  have  negative  effects  on  sustainability  goals,  such  as 
increased  health  burden  due  to  insufficient  control  of  infectious  diseases,  and  increased  food 
waste due to decreased variety of preservatives. 

  An  industry  and  a  civil  society  organisation  expressed  the  need  for  a  broad  approach  to 

sustainability assessment, including the need to improve the circular economy.  

  For research  to be efficient and cost-effective, cooperation  and co-ordination  is required  among 
the  key  stakeholders,  within  the  EU  and  globally,  to  pool  knowledge  and  avoid  duplication  of 
efforts. 

*Respondents  to  all  three  surveys  (citizens,  stakeholder  and  SME  surveys)  were  self-selected  and  thus  not 
necessarily representative of the full range of views of these groups. 

91 

 
 
 
 
 
 
 
 
 
Box 6.2: Trade impact case studies 

As a contribution to the Fitness Check, the JRC carried out two case studies aimed at exploring the 
feasibility  of  economic  analysis  to  identify  associations  between  the  implementation  of  risk 
management measures on selected chemicals and trade flows, both within the EU and between the EU 
and non-EU countries. The first case study considered four low molecular weight (LMW) phthalates 
commonly used as plasticisers (DEHP, DBP, BBP and DIBP), which have been inter alia subjected to 
a series of restrictions since 1999. The second case study focused on 3-Benzylidene Camphor (3-BC), 
a UV filter used in sunscreen products, which has been subject to a ban under the Cosmetic Products 
Regulation since 2015 and was identified as SVHC under REACH in 2018.  

The approach applied the “gravity model” which is a well-established methodology in economics. A 
particular challenge, however, was due to the level of aggregation of the input trade data (in the UN 
Comtrade  database).  Since  the  trade  flow  data  relate  to  baskets  of  commodities,  rather  than  the 
specific chemicals of interest, it was necessary to choose a proxy for the chemicals of interest (namely 
plasticisers for LMW phthalates, and cosmetic/toilet preparations for 3-BC). 

The results showed a downward trend in the trade flows of plasticisers which started before the 1999 
intervention,  making  it  difficult  to  judge  whether  the  intervention  contributed  to  this  trend. 
Conversely,  the  results  showed  increased  trade  flows  of  cosmetic/toilet  preparations  following  the 
2015 intervention on 3-BC. While this is consistent with the conclusion that the ban of the UV filter 
positively  impacted  on  the  trade  cosmetic/toilet  preparations,  uncertainties  relate  to  the  extent  to 
which 3-BC was present in those products, as well as confounding socioeconomic factors.  

These case studies illustrate some of the challenges in using economic analysis to identify the trade 
impacts of regulatory interventions. They also point to the need for higher resolution trade data, closer 
to the chemical and commodity of interest, as well as information on the market share of the chemical 
of interest in various commodities or baskets of commodities. However, obtaining such data could be 
problematic as they are typically commercially sensitive. 

The  two  case  studies,  including  methodological  details  of  the  economic  analysis  and  associated 
uncertainties, are further described in (Canzian et al., 2020).  

92 

 
 
 
 
 
 
 
 
 
7  RELEVANCE 

  Societal  concerns  about  chemicals  in  general  are  high.  Concerns  on  EDs  have  received 
societal  attention,  especially  in  certain  MS  (France,  Nordic  countries),  and  political  support 
from  EU-level  institutions  including  the  European  Parliament,  the  EU  Committee  of  the 
Regions, as well as the Commission. Citizens engaged in the topic lack trust in the ability of 
EU  legislation  to  achieve  its  objectives  of  human  health  and  environmental  protection. 
Economic  stakeholders  are  concerned  that  the  lack  of  trust  in  EU  regulatory  processes 
undermines science-based decision making. 

  A  sustained  global  increase  in  chemical  manufacturing  is  expected,  primarily  in  Asia.  
Imports of chemicals and products into the EU are increasing. Assessing and ensuring the safe 
use of hazardous chemicals including EDs in global material streams through subsequent life 
cycles is essential to achieve the benefits of a more circular economy. 

  The  next  generation  of  EU  funded  research  strives  to  address  realistic  mixture  (combined) 
exposure scenarios and to embrace the multi-factorial nature of certain indicators of concern, 
such as the increase in certain non-communicable diseases and the decline in biodiversity. To 
improve  the  chance  of  establishing  (or  ruling  out)  causal  links,  exposure  to  environmental 
mixtures of EDs need to be assessed, ideally in conjunction with other stress factors. Building 
on the currently available methods developed in key research areas (e.g. use and interpretation 
of  human  biomonitoring  data,  effect-based  methods  in  water  quality  assessments)  the 
Commission  is  exploring  new  mechanisms  to  use  emerging  knowledge  in  the  policy  cycle 
(e.g. the candidate European Partnership for Chemicals Risk Assessment).  

Q5.  To  what  extent  do  the  EU  legal  provisions  on  and  approaches  to  EDs  take  into  account 
health and environmental concerns, and social and economic consequences that are relevant to 
citizens and stakeholders? 

  Relevance to citizens and stakeholders 

7.1
The  overall  objectives  of  human  health  and  environmental  protection  enshrined  in  EU  chemical 
legislation  remains  relevant  to  EU  citizens.  According  to  a  Eurobarometer  survey  conducted  in 
December  201976,  nine  in  ten  Europeans  are  worried  about  the  impact  of  chemicals  present  in 
everyday products on the environment; a slightly smaller proportion (85%) is worried about impacts 
on  their  health  (the  survey  question  concerned  the  overall  impact  and  did  not  query  ED  effects 
specifically).  Societal  concerns  on  EDs  have  received  attention  and  political  support  in  the  recent 
resolution  by  the  European  Parliament77  and  the  opinion  of  the  European  Economic  and  Social 
Committee78 and the European Committee of the Regions79. 

76Eurobarometer 2020: 
https://ec.europa.eu/commfrontoffice/publicopinion/index.cfm/survey/getSurveydetail/instruments/special/surve
yky/2257  
77European Parliament resolution 2019/2683(RSP) 
78European Economic and Social Committee NAT/754-EESC-2018-05760 
79European Committee of the Regions 2019/C 404/07 

93 

 
 
 
 
 
                                                      
Perspectives  on  the  importance  of  regulating  EDs  are  polarised  between  stakeholders  representing 
citizens  and  civil  society organisations  and  those  representing  business  organisations  (see  Box  7.1). 
The discrepancy between the views of citizens engaged on the topic and business organisations appear 
to reflect different opinions about how to apply the precautionary principle and how to deal with the 
uncertainties in quantifying risks associated with exposure to EDs (such as the issue of whether EDs 
have a threshold effect or not). All parties, however, agree on the need to enhance the exchange on the 
latest  science  (e.g.  ED  stakeholders  forum)  and  the  collaboration  among  authorities  and  between 
authorities and stakeholders.  

The  Commission  and  the  European  Agencies  regularly  involve  citizens  and  other  stakeholders 
through public consultations at different steps of the policy cycle from new legislative proposals, to 
scientific  evaluation  and  decisions,  including  EFSA  opinions,  biocide  evaluations,  REACH  SVHC 
proposals, restriction regulations, and authorisations decisions. 

Box 7.1: Stakeholder views on the relevance of EU legislation on endocrine disruptors* 

Among respondents to the public consultation, 61% think they are less protected from EDs compared 
to  other  toxic  chemicals.  Despite  the  EU  laws’  ambition  to  achieve  a  high  level  of  protection 
including for all vulnerable groups, the percentage of respondents who think that a high or a moderate 
level of protection is achieved range between 15% (for adolescents) to 30% (for new-borns up the age 
of  3)  with  relatively  small  differences  between  the  general  population  (adults  in  general,  20%)  and 
other  sub-populations  (elderly,  children  in  puberty,  people  at  work,  people  with  illness,  unborn 
through  exposure  during  pregnancy  and  pregnant  women).  Even  lower  is  the  percentage  of 
respondents who think that EU legislation achieves a high level of protection for wildlife, with small 
differences among categories of wildlife, ranging between 6% (invertebrates such as snails, shrimps 
and  worms)  and  14%  (mammals).  Seventy-five  percent  of  respondents  to  the  public  survey  believe 
that  EDs  contribute  to  a  large  extent  to  some  human  diseases/health  conditions  such  as  infertility, 
cancer or obesity (and 18% to a moderate extent). 

in 

the  figures  below.  In  both  cases, 

The  perspectives  of  different  stakeholders  about  the  relative  importance  of  EDs  as  a  stress  factor 
contributing  to  human  health  condition/disease  and  to  the  observed  decrease  in  biodiversity  is 
illustrated 
the  vast  majority  of  public  authorities, 
academic/research institutions, civil society organisations and trade unions think that EDs contribute 
to  a  significant  extent,  in  comparison  with  other  factors.  The  majority  of  companies/business 
organisations  and  business  associations  think  that  EDs  do  not  make  a  relatively  large  contribution. 
The  different  opinions  by  companies  and  business  associations  compared  to  the  other  stakeholder 
groups may be explained by their positive opinion about the effectiveness of legislation or by different 
interpretations of the question (i.e. company or sector specific). 

94 

 
 
 
The  scientific  debate  has  polarised  perspectives  from  different  stakeholder  groups,  with  all  sides 
arguing that science supports their opinions. On one side, respondents from civil society organisations 
and most scientific stakeholders state that legislative developments do not match the “unanimous call 
from the scientific community”. On the other side economic stakeholders (business organisations, EU 
trading partners) are concerned that "legislation begins to be based on societal concern rather than on 
science".  

Some  citizens,  civil  society  organisations,  trade  unions  and  academics/research  institutions  claimed 
that  there  is  limited  information  available  on  ED  in  products,  while  human  and  environmental 
exposure to EDs is ubiquitous. Some respondents from these stakeholder groups expressed concerns 
about their potential association with the increase of non-communicable disease and the related high 
health costs, as reported for example by the Endocrine Society (Gore et al., 2015). According to some 

95 

 
 
 
 
 
 
NGOs,  the  current  situation  makes  it  "almost  impossible  for  consumers  to  avoid  these  harmful 
chemicals".  Most  civil  society  organisations  are  concerned  that  the  current  legislative  framework 
provides an uneven level of protection across regulated sectors and therefore fails to achieve a high 
level of protection by minimisation of exposure, as laid down in the EU 1999 strategy. Almost 90% of 
respondents to the public consultation think that the EU needs to step up its efforts to reduce human 
exposure; the percentage is only slightly lower (86%) for environmental exposure.   

Respondents to the stakeholders consultation from business organisations expressed concern about the 
trade-offs  of  hazard-based  risk  management,  including  economic  impacts  (e.g.  disproportionate 
increase  in  production  costs,  such  as  due  to  regulatory-induced  substitution),  societal  impacts  (e.g. 
reduced shelf life of blood bags without DEHP), environmental impacts (e.g. increased waste due to 
reduced  product  lifetime  without  effective  preservation,  regrettable  substitution).  They  are  also 
concerned about the lack of citizens’ trust in EU regulatory decision-making, the gaps in the market 
surveillance activities especially at the EU border, the consequences of “stigmatising” substances that 
are undergoing risk assessment, and the difficulty in operating in a framework with a "continuously 
moving goal target".  

*Respondents  to  all  three  surveys  (citizens,  stakeholder  and  SME  surveys)  were  self-selected  and  thus  not 
necessarily representative of the full range of views of these groups. 

Q6.  To  what  extent  do  the  EU  legal  provisions  on  and  approaches  to  EDs  take  into  account 
evolving  needs  (e.g.  transition  to  circular  economy)  and  the  latest  scientific  findings  (e.g. 
developments  in  chemical  mixtures  and  grouping  assessments,  biomonitoring,  effect  based 
methods, etc.)? 

  Ability to adapt to the evolving societal and economic context 

7.2
Societal concerns on chemicals in general and on EDs reflect the high expectations of Europeans for 
ambitious  health  and  environmental  policies.  The  EU  is  a  global  leader  in  environmental  and 
consumer  protection  policy.  The  political  agenda  set  by  the  Von  der  Leyen  Commission  aims  at 
firmly  setting  the  EU  on  a  new  path  of  sustainability,  inclusive  growth  and  healthy  lifestyles.  The 
action  plan  outlined  in  the  European  Green  Deal80  comes  with  significant  economic  and  societal 
transformations. Many core elements of the Green Deal, including the zero-pollution ambition for a 
toxic-free environment, the farm to fork strategy, clean and circular economy81, and the protection of 
ecosystems and biodiversity are interlinked with the chemical policy agenda in general and with EDs 
in particular. Another societal trend relevant to ED management is the decline in population growth 
due  to  low  fertility  rates  across  much  of  the  EU82.  In  parallel  to  these  trends,  changes  in  global 
patterns of production and consumption have accelerated in recent years. Global chemical production 
has  grown  in  recent  years  and  is  expected  to  almost  double  from  2017  to  2030  (UNEP,  2019). 
Projected  growth  will  be  highest  in  Asia,  with  China  estimated  to  account  for  almost  50  percent  of 
global  sales  by  2030.  The  imports  of  consumer  goods  and  other  articles  into  the  EU  have  tripled 

80COM(2019) 640 
81EU Circular Economy Action Plan. https://ec.europa.eu/environment/circular-economy/index_en.htm 
82https://ec.europa.eu/eurostat/statistics-explained/index.php?title=Fertility_statistics 

96 

 
 
 
 
                                                      
between  2000  and  2015  creating  additional  challenges  for  managing  the  risks  associated  with  the 
presence of hazardous substances in articles83. 

Many  functional  chemicals  that  have  raised  concerns  for  their  negative  impact  on  the  circular 
economy,  including  plasticisers  (e.g.  DEHP  and  other  low  molecular  weight  phthalates),  flame 
retardants  (e.g.  polybrominated  diphenyl  ethers),  water  repellents  (e.g.  perfluoroalkyl  substances), 
preservatives and other biocides, have been assessed for their endocrine disrupting properties (Milieu 
Ltd  et  al.,  2017)  (sub-study  b).  The  intentions  to  strengthen  the  single  market  for  secondary  raw 
materials  and  in  general  the  inclusion  of  circular  economy  considerations  into  chemicals  risk 
management  will  require  a  transformation  of  the  life  cycle  stages  and  timescales  considered  in  risk 
assessment83.  Exposure  data  in  REACH  dossiers  fail  in  many  cases  to  cover  all  relevant  exposure 
situations  along  the  supply  chain84.  Exposure  information  on  substances  in  waste  and  in  recycled 
material streams is even more limited. Both information gaps are evidently at odds with the circular 
economy ambitions: it is difficult to conclude on long-term safety and sustainability of substances of 
concern  (e.g.  SVHC)  without  the  ability  to  track  their  mass  flows  in  material  cycles  and  in  the 
environment.  

Hence,  efforts  to  control  hazardous  chemicals  (e.g.  SVHC)  in  materials  and  products  and  recycled 
material streams need to step up to achieve the objectives of the circular economy85. The scale of the 
problem is significant and regards both legacy chemicals present in recycled material streams (Milieu 
Ltd et al., 2017) (sub-study b) and chemicals produced and used today, specifically those authorised 
for specific uses, if they are not managed in closed and controlled material cycles. The problem is also 
likely to increase, considering that the amount of recycled materials used in the EU needs to increase 
substantially  from  the  current  12%Error!  Bookmark  not  defined..  The  EU  Circular  Economy  Action  Plan 
further stresses the need for action to ensure that the EU does not export its waste challenges to third 
countries and to facilitate preparing for re-use and recycling of waste in the EU86.  SVHCs in recycled 
materials  have  been  regulated  through  REACH  authorisation  and  restrictions,  as  was  the  case  for 
authorised uses of recycled PVC containing DEHP and for the exemption of recycled textiles from the 
restriction  of  nonylphenol  ethoxylates  (Annex  5B  and  5C,  DEHP  and  NP  case  studies).  In  other 
cases, however, and especially for heterogeneous waste, information on the presence of substances of 
concern  is  lost  or  not  available  to  waste  operators  by  the  time  products  become  waste.  The 
establishment  of  the  SCIP  database  on  “Substances  of  Concern  In  articles  as  such  or  in  complex 
objects  (Products)”  under  the  waste  framework  directive  is  an  important  first  milestone  in  this 
direction as it intends to help waste operators in waste separation87. 

  Ability to adapt to scientific progress 

7.3
Recent  policy  evaluations  concluded  that  the  framework  has  generally  been  able  to  adapt  to  the 
evolving  scientific  progress88  89.  The  question  is  particularly  important  in  the  context  of  EDs, 
considering  the  increasing  resources  dedicated  to  scientific  research  on  EDs  over  the  last  two 
decades90.  All  three  case  studies  (Annex  5)  provide  examples  of  recent  regulatory  assessments 

83SWD(2019) 199 
84SWD(2018) 58 
85SWD(2019) 199 
86EU Circular Economy Action Plan. https://ec.europa.eu/environment/circular-economy/index_en.htm 
87Directive (EU)2018/851 amending Directive 2008/98/EC on waste 
88SWD(2018) 58 
89SWD(2019) 199 
90RTD Factsheet: EU Research on Endocrine Disruptors: https://ec.europa.eu/info/files/eu-research-endocrine-
disruptors-factsheet_en 

97 

 
 
                                                      
including  reviews  of  all  available  evidence  in  the  open  scientific  literature.  Academic  studies, 
however,  often  miss  to  include  critical  parameters  as  described  in  standard  guidelines  and  are 
consequently given a lower consideration  in  weight of evidence assessments (e.g.  Annex 5A, 3-BC 
case study).  

The  consideration  of  new  scientific  evidence  is  usually  more  problematic  for  academic  studies  on 
human  biomonitoring,  (eco)epidemiological  studies,  studies  addressing  exposure  to  mixtures, 
biomarkers of effects, or effect-based methods in ecotoxicology. Current standard test and assessment 
methods typically on single substance assessments which do not fully exploit the value of these types 
of studies91.  

Long-term  low  dose  exposure  to  ED  mixtures  is  a  well-recognised  challenge  in  both  regulatory 
toxicology and ecotoxicology92. The scope of mixture assessment and management within the existing 
framework  is  mostly  limited  to  intentional  mixtures  within  single  policy  domains,  even  though  the 
potential  for  aggregate  and  combined  (mixture)  exposures  across  policy  domains  is  well  known 
(Figure 3.1). 

Unintentional  mixtures  are  considered  in  some  legislation,  including  for  pesticide  residues  (MRLs) 
plant protection products and biocidal products. However, practical examples are mostly limited to the 
legislation on MRLs, where methodology is so far established for two cumulative assessment groups 
(effects  on  nervous  system  and  on  thyroid)  and  some  recent  examples  of  grouping  assessments  and 
management processes (e.g. phthalates regulated under REACH and FCMs, PFAS, etc.)  (Annex 5B, 
DEHP case study). An increasing number of academic studies explore how to incorporate assessments 
of complex and realistic ED mixture exposure scenarios in regulatory assessments (Bopp et al., 2019; 
Ganzleben et al., 2017; Gennings et al., 2018).  

Translating  new  scientific  findings  about  the  effects  of  combined  exposure  to  EDs  into  regulatory 
action conflicts with a framework designed to assess one substance at a time and to implement risk 
management  measures  across  multiple  regulated  sectors.  Addressing  this  challenge  might  require  a 
complete  rethink  of  the  way  in  which  risk  assessment  and  management  of  chemicals  mixtures  is 
currently  performed  (Bopp  et  al.,  2019).  One  promising  advancement  in  the  monitoring  field  is  the 
development  of  effect-based  methods,  which  might  be  used  in  combination  with  effect-directed 
analysis  in  water  quality  assessment  under  the  WFD  (Brack  et  al.,  2017;  Hamers  et  al.,  2018).  The 
oestrogen  receptor  transactivation  assay  has  been  recommended  by  the  JRC  as  a  suitable  in  vitro 
method  to  determine  estrogenic  activity  of  water  samples  (European  Commission,  2014).  Other  in 
vitro assays to determine (anti)androgenic and thyroid hormone disruption  have been  also proposed 
for  both  environmental  (Hamers  et  al.,  2018)  and  human  health  applications  (Hamers  et  al.,  2020). 
The method opens potential synergies between the water and chemicals legislation in the assessment 
of environmental effects of EDs. Similarly, in human biomonitoring some integrative biomarkers of 
effect  have  been  proposed  as  an  early  marker  of  endocrine-mediated  health  effects  (Baken  et  al., 
2019).  

A major scientific challenge in estimating the impact of chemical stress is the multi-factorial nature of 
negative  trends  of  concern  such  as  the  increase  of  non-communicable  diseases  (Slama  et  al.,  2017) 
and  the  decline  in  biodiversity  (Posthuma  et  al.,  2016).  To  disentangle  the  contribution  of  multiple 
stress factors, chemical mixture exposure must be assessed in combination with other factors, referred 

91COM(2019) 199 
92COM(1999) 706 

98 

 
 
 
                                                      
to  as  confounding  factors  in  (eco)epidemiological  research.  Statistical  methods  to  account  for 
confounding  factors  have  been  developed  and  applied  in  recent  (eco)epidemiological  research 
addressing EDs exposure (Demeneix and Slama, 2019; Gennings et al., 2018; Slama et al., 2017).   

The next generation of EU funded research is taking a more holistic consideration of environmental 
stressors on disease burdens. Examples include the Health Environment Research Agenda for Europe 
(HERA93)  and  the  candidate  European  Partnership  for  Chemicals  Risk  Assessment94.  The 
Commission is exploring new mechanisms to distil emerging streams of scientific evidence into the 
policy  cycle  (e.g.  HBM4EU95  and  the  candidate  European  Partnership  for  Chemicals  Risk 
Assessment).  The  issue  goes  beyond  the  well-known  obstacles  encountered  in  the  development  and 
validation of novel test methods. 

Box 7.2. Stakeholder views on the ability of the framework to adapt to scientific progress* 

Stakeholders are split between those who think the framework is able to consider the latest scientific 
developments (46%) and those who think it is not (54%).  

Several business organisations and public authorities consider that processes embedded in the policy 
cycle  allow  for  updates  of  regulations  and  guidance  to  account  for  new  scientific  knowledge  and 
methods.  Many  stakeholders,  however,  complain  about  the  lengthy  process  of  validation  and 
regulatory uptake of new test methods developed under the OECD programme. Several stakeholders 
suggest that building on the ECHA and EFSA experience, enhanced collaboration between agencies 
and  stakeholders  can  spearhead  uptake  of  new  scientific  methods.  According  to  some  stakeholders, 
the implementation of the criteria adopted in 2018 and the related joint EFSA and ECHA guidance is 
currently  too  rigid  and  does  not  encourage  the  uptake  of  new  information  and  the  evaluation  of  its 
relevance. Some stakeholders call for revisions of the guidance to adapt it for specific considerations 
(e.g. metal characteristics) and in general to ensure additional data requirements bring added value to 
the assessment and do not result in unnecessary animal testing.  

Stakeholders widely recognise that provisions exist in regulatory assessments that require in principle 
the consideration of all available scientific evidence. The extent to which such provisions are applied 
in practice is debated. Regulators place higher confidence on standard, validated test methods because 
of easier interpretation and reproducibility of results. According to several civil society organisations, 
scientific  stakeholders  and  some  public  authorities,  regulators  are  reluctant  to  consider  information 
from  non-standard  methods.  One  respondent  pointed  out  that  “with  the  current  gaps  in  the  data 
requirements,  dismissing  such  information  from  the  academic  literature  risks  to  misclassify  a 
dangerous substance as a non-ED”.  
*Respondents  to  all  three  surveys  (citizens,  stakeholder  and  SME  surveys)  were  self-selected  and  thus  not 
necessarily representative of the full range of views of these groups. 

93https://www.heraresearcheu.eu/key-objectives 
94https://ec.europa.eu/info/files/european-partnership-chemicals-risk-assessment_en 
95https://www.hbm4eu.eu/  

99 

 
 
 
 
 
                                                      
8  EU ADDED VALUE 

  Regulating EDs at EU level contributes to ensuring an equal level of protection across the EU 

Member States regarding human and environmental health.  

  Furthermore,  better  scientific  consistency  in  the  assessments  and  more  efficiency  can  be 
achieved by joining forces in testing capacities, experience and knowledge across the Member 
States. 

  There have been cases of unilateral measures at Member State level for a few ED substances, 

such as Bisphenol A and DEHP.  

  Stakeholders  expressed  a  strong  wish  to  avoid  unilateral  measures  where  possible,  but  also 
agreed that if individual Member State level decisions are taken, e.g. to avoid delays in finding 
agreement  at  EU  level,  such  decisions  should  be  followed  up  at  EU  level  to  come  to  a 
harmonised approach.  

  EU-level  follow  up  to  unilateral  decisions  should  happen  in  a  timely  manner,  to  minimise 
disruption  to  the  single  market  and  to  ensure  an  equal  level  of  protection  throughout  the 
Member States. 

Q7. What is the added value of regulating EDs at EU rather than Member State level? 

Regulating  EDs  at  EU  rather  than  Member  State  level  is  adding  value  in  various  ways.  The 
Commission evaluations, carried out recently across various pieces of legislation for different sectors 
(e.g. REACH, non-REACH chemical legislation, plant protection products, etc.), have all concluded 
that a unique chemicals legislation centralised at the EU level has in general proven largely successful 
in  terms  of  the  protection  of  human  health  and  the  environment  as  well  as  the  functioning  of  the 
internal market96.  

8.1

  Joining forces and efficient use of resources 

The assessment of EDs requires a high level of scientific expertise and experience. The sharing and 
pooling of knowledge and resources and the application of common rules and standards across the EU 
has resulted in significant positive economic, health and environmental impacts that would not have 
been possible to achieve on the basis of legislation at the Member State level alone, as concluded for 
chemicals  in  general  in  the  Fitness  Check  of  non-REACH  Chemicals  legislation97.  Thus,  regulating 
the risk assessment and management of EDs at EU level also increases efficiency. It helps to avoid 
duplication  of  efforts  at  Member  State  level  and  improve  the  state  of  knowledge,  quality  and 
availability  of  data  needed  for  risk  management  decision  making.  It  also  provides  a  clearer 
overarching framework for companies operating across different Member States, so that they do not 
need to adapt to multiple potentially diverging national rules. An EU level approach offers advantages 
in terms of effectiveness by avoiding a fragmented approach in a market where firms are increasingly 
cross-border in their outlook98. The costs of achieving the objectives to protect human health and the 

96SWD(2019) 199 
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100 

 
 
 
 
 
 
 
                                                      
environment are considered to be lower than in a system where each Member State conducts the risk 
assessments on its own (Ecorys, 2018). A uniform EU approach also strengthens the EU’s position in 
chemicals regulation worldwide, which also has benefits for the EU chemical industry. 

Reaching a consensus at EU level in regulating EDs also plays a role in preventing unfair competition 
between  Member  States  and  leads  to  an  equal  level  of  protection  for  citizens  and  the  environment 
throughout  all  Member  States.  Since  the  adaptation  of  sector-specific  legislation  to  new  scientific 
evidence  regarding  risks  of  endocrine  disruptors  requires  a  certain  amount  of  time,  measures  for 
protecting  health  and  the  environment  can  be  taken  by  more  general  provisions  in  EU  legislation, 
namely  under  the  General  Product  Safety  Directive  in  the  case  of  products,  and  under  the  General 
Food Law in the cases of food and feed. 

8.2

  Preserving the functioning of the single market 

There  have  been  cases  of  unilateral  measures  at  Member  State  level  for  a  few  ED  substances. 
Bisphenol  A  is  the  most  relevant  example;  its  use  has  been  banned  in  specific  consumer  products 
aimed  at babies or young children in France, Denmark, Austria,  Belgium and Sweden  –  and for all 
age  groups  in  France.  Some  Member  States,  such  as  Italy  and  Denmark,  have  also  taken  ‘soft’ 
measures at the national level, such as providing advice to the public, creating incentives for industry 
for the development of safer alternatives or the promotion of voluntary agreements (Brunel University 
London  and  DTU  Food  National  Food  Institute  Denmark,  2016;  UNEP  IPCP,  2017).  In  2011, 
Denmark  proposed  to  restrict  the  use  of  four  phthalates  (DEHP,  BBP,  DBP,  DIBP)  in  consumer 
articles in the EU. However, ECHA's Risk Assessment Committee concluded that the "available data 
does not indicate that there is currently a risk from combined exposure to the four phthalates" and did 
not  support  the  restriction99.  In  the  following,  Denmark  subsequently  planned  to  ban  the  four 
phthalates unilaterally. However, it dropped the plan in 2015 since it was not in line with the rules set 
by REACH (ECPI, 2014). The safeguard clause of REACH stipulates that a Member State can take 
unilateral measures if it has grounds for believing that urgent action is needed to protect human health 
or the environment. This triggers a decision taken via Comitology procedure on whether the unilateral 
measure  should  be  revoked  or  authorised  for  a  certain  time  period.  This  decision  has  to  be  taken 
within 60 days. If the measure is a restriction and if it is authorised, the Member States which took the 
unilateral decision should initiate the procedure for an EU-wide restriction under REACH. Similarly, 
unilateral  action  by  MSs  that  contradict  EU  rules  must  be  followed  up  at  EU  level  for  FCMs,  for 
example in the case of bisphenol A. 

Moreover,  after  considering  results  from  FCMs  inspection  and  control  project,  on  September  2019, 
the Danish Ministry of Environment and Food announced that the Danish government will ban the use 
of  any  per-  and  polyfluoroalkyl  substances  (PFAS)  in  paper  and  cardboard  used  in  food  contact 
materials  by  July  2020100  due  to  inter  alia  the  concerns  on  the  suspected  endocrine  disrupting 
properties  for  human  health  and  the  environment  and  evidence  of  bioaccumulation.  The  European 
Commission published a recommendation on a coordinated control plan to determine the prevalence 

99https://newsletter.echa.europa.eu/home/-/newsletter/entry/2_14_denmark-advises-on-how-to-limit-phthalates-
of-concern 
100https://mfvm.dk/nyheder/nyhed/nyhed/foedevareministeren-er-klar-til-at-forbyde-fluorstoffer/  

101 

 
 
 
 
 
 
 
                                                      
of certain substances migrating from or present in FCMs—including the fluorinated compounds per- 
and  polyfluoroalkyl  substances  (PFAS)—into  food,  in  May  2019101.  Notably,  PFOA  has  been 
restricted for use in the production and placing on the market of articles, including FCMs from July 4, 
2020 under REACH.  Regulatory  action  on  multiple  other  PFAS  has  been  launched  or  already  been 
concluded (REACH Regulation, Regulation (EU) 2019/1021). 

More  recently,  France  has  also  launched,  based  on  its  Second  National  Strategy  on  Endocrine 
Disruptors  key  measures  (  Ministère  de  la  Transition  Ecologique  et  Solidaire  et  Ministère  des 
Solidarités et de la Santé", 2019) (Annex 1), a project to draw up a list of chemicals that may present 
ED-properties to better manage risks depending on the degree of proof and the level of uncertainties 
(to be ready by 2021). This is intended to inform recommendations for appropriate management (for 
example, by considering a recognition in European regulation, by reducing use as a precaution, or by 
pursuing  more  in-depth  assessment)  of  suspected  or  presumed  EDs.  This  includes  also  a 
recommendation to inform citizens about the chemicals, notably endocrine disruptors, to be found in 
everyday consumer products. 

Unilateral  measures  are  triggered  by  provisions  (safeguard  clauses) that  are  included  on  purpose  in 
legislation to allow Member States to act first. There is insufficient evidence to estimate the overall 
impact  of  the  unilateral  measures  described  above.  However,  such  unilateral  measures  should 
be followed up at EU-level as fast as possible to minimise any disruptive effects on the single market. 

The  stakeholders  answering  the  survey  expressed  a  strong  wish  to  avoid  unilateral  measures  where 
possible.  If  they  are  taken  by  individual  Member  States  as  a  precautionary  measure,  e.g.  to  avoid 
delays in finding agreement at EU level, such measures should be followed up at EU level. Even soft 
measures  such  as  publishing  advice  on  the  use  of  products  containing  certain  chemicals  can  have  a 
strong  influence  on  consumer  behaviour.  However,  a  Eurobarometer  survey  (Nr.  456)  on  Chemical 
Safety of 2019102 showed that EU citizens consider products manufactured in the EU to contain safer 
chemicals than those imported from outside the EU. This indicates a higher level of confidence in the 
EU regulatory framework for manufactured products compared to regulatory regimes abroad103 (EC 
2019). 

Also in the public consultation related with this Fitness Check, 6 out of 474 respondents104 provided 
free text comments related to the EU added value. Even if they are mostly in favour of regulating EDs 
at  EU  level  in  a  uniform  way  across  Member  States,  they  raised  two  issues.  Firstly,  they  state  that 
there  is  no  full  implementation  of  EU  rules  in  each  Member  State  and  putting  EU  legislation  into 
practice need to be accelerated. Secondly, citizens seem to be worried about imported products from 
non-EU  countries  with  less  stringent  rules  and  ask  for  more  controls  and  enforcement  to  ensure 
imported products comply with EU requirements. 

8.3

  Legislative measures alignment between Europe and global regimen 

101Recommendation on Coordinated Control Plan for Certain Substances Migrating from FCMs. (EU) 2019/794 
102http://ec.europa.eu/commfrontoffice/publicopinion/index.cfm/resultdoc/download/documentky/78786 
103SWD(2019) 199 
104Four comments were from individual citizens, two from NGOs 

102 

 
 
 
 
 
 
 
 
                                                      
The  EU  chemicals  legislation  has  become  a  reference  point  for  international  standards  in  several 
areas,  which  helps  to  reduce  potential  trade  frictions  as  well  as  address  transboundary  chemical 
related  issues.  REACH  for  example  has  influenced  legislation  in  a  few  third  countries  (e.g.  South 
Korea),  although  significant  differences  exist  and  there  is  room  to  further  exploit  the  potential  of 
REACH to serve as a global model for chemicals legislation105.  

European  companies  also  benefit  from  the  perceived  quality  of  EU  products  in  non-EU  country 
markets, which has brought important advantages in terms of international trade. The EU chemicals 
legislation  has  also  helped  to  decrease  the  barriers  to,  and  costs,  of  intra-EU  trade  by  limiting  the 
application  of  multiple  and  potentially diverging  national  rules  with  limited  territorial  coverage  and 
existing only in the applicable national language(s)106. 

However, there are also concrete examples of problems at international level, e.g. in the area of Plant 
Protection  Products  and  Maximum  Residue  Levels  (MRLs).  Non-EU  countries  often  remind  the 
Commission that non-approval decisions and setting of MRLs need to respect WTO principles. The 
issue of cut-off criteria, including the criteria to identify endocrine disruptors, has been the subject of 
acrimonious discussion in the WTO-TBT and WTO-SPS Committees since 2013. Between 2015 and 
2017,  in  the  WTO  Committees,  non-EU  countries  raised  specific  trade  concerns  on  pesticides  208 
times against the EU. This should be compared with two specific trade concerns on pesticides raised 
by  the  EU  against  other  countries.  Although  decisions  under  the  MRL  Regulation  are  based  on 
assessments  of  risk  only,  the  effects  of  the  cut-off  criteria  applied  under  the  PPP  Regulation  with 
subsequent lowering of MRLs, is perceived by third countries to result in inconsistency between the 
EU  and  WTO.  However,  the  extent  of  this  inconsistency  is  currently  unproven  as  so  far  no  active 
substance has not been approved (or approval not renewed) based solely on the cut-off criteria107. 

Box 8.1: Stakeholder views on reasons for regulating EDs at EU level* 

EU level regulation of EDs is needed in order to: 

 

 

 

achieve an  equal level of  protection across the EU  Member States for human health and the 
environment in accordance with the precautionary principle; 
react  to  the  knowledge  gaps  around  EDs,  such  as  epigenetic  and  transgenerational  effects, 
combined effects, limitation of assessing specific modes of actions in particular beyond EATS; 
share  capacities  in  testing  and  assessment,  experience  and  knowledge  across  the  EU  to 
guarantee consistency, predictability, efficiency and credibility and thus avoid disputes; 
support  achieving  the  overall  Commission  Priorities  of  e.g.  Zero  Pollution  ambition, 
biodiversity strategy and farm to fork strategy and facilitate the circular economy; 
ensure  competitive  industry,  preserve  the  EU  single  market,  and  stimulate  EU  wide  safe 
innovation initiatives; 
 
allow more efficient implementation of control measures and improve overall enforcement; 
  provide  stronger  signal  to  non-EU  countries  to  support  globally  safer  use  of  chemicals  and 

 

 

setting a global example. 

*There  were  no  clear  trends  according  to  stakeholder  group.  This  is  a  summary  of  the  most  frequently 
mentioned free text comments. 

105SWD(2018) 58 
106SWD(2018) 58, part 5 
107SWD(2020) 87  

103 

 
 
 
 
 
 
                                                      
 
Box 8.2: Stakeholder and SME views on the impact of unilateral actions at national level* 

In the stakeholder survey, the question of impacts of unilateral actions at national level was asked 
only  to  business  associations  and  company/business  organisations.  Of  those  who  answered  the 
questions, 48% stated that their organisation had been impacted, while 52% stated they had not been 
impacted. 

Several business associations and company/business organisations highlighted examples of unilateral 
Member State actions that had a direct or indirect impact on their business. Examples are:  

1) the French Ban of BPA in Food Contact Materials  
2) the Danish ban of propyl and butyl paraben in cosmetic products 
3)  the  ban  of  some  Plant  Protection  Products  in  MSs  even  if  the  product  is  approved  by  mutual 
recognition in the respective regulatory zone.  

One  direct  impact  is  the  direct  pressure  to  eliminate  substances  from  the  production  sometimes 
without the availability of appropriate alternatives.  

In addition, unilateral bans may also create shifts in wider consumer behaviour. For example, even if 
bans are limited to specific uses, consumers’ concerns lead to avoid the use of the limited substance in 
all  types  of  products  thus  reducing  trust  in  the  safety  of  a  chemical  EU  wide.  This  can  also  occur 
when MS authorities draw up lists of chemicals of concern or with suspected ED properties. 

In the SME survey, only three of 70 SMEs answered that individual Member State initiatives have 
affected their companies. Sixty-five stated there were no effects on their companies, two did not reply 
to the question. The three SMEs stating they were affected were two large enterprises (with more than 
250 employees) and one medium size enterprise (with 50-249 employees). 
*Respondents  to  all  three  surveys  (citizens,  stakeholder  and  SME  surveys)  were  self-selected  and  thus  not 
necessarily representative of the full range of views of these groups. 

104 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Box 8.3: Stakeholder views: Are national level unilateral actions by Member States on specific 
EDs justified?* 

In order to achieve an equal level of protection of humans and the environment throughout Europe, 
endocrine disruptors should be regulated centrally at EU level. This is with the intent to ensure and 
preserve the single market within the European countries, avoiding the introduction of non-tariff trade 
barriers.  However,  unilateral  actions  at  national  level,  aimed  to  restrict  or  ban  substances  with  ED 
properties, have been recently taken in some of the Member States.  

The  Stakeholder  Survey  revealed  that  36%  of  the  stakeholders  agreed  that  unilateral  actions  by 
individual  Member  States,  such  as  banning  chemicals  because  of  ED  properties,  are  not  justified. 
However, 26% of stakeholders replied that this is justified since the protection of human health or the 
environment is more important than preserving the integrity of the single market. Another 36% stated 
that unilateral actions are justified in certain circumstances when those are followed by wider actions 
at  EU  level  to  preserve  the  single  market.  Very  few  (4  out  of  165)  respondents  believed  regulating 
EDs at EU level is not justified. 

Many stakeholders indicated  that ideally all measures taken to protect humans and the environment 
from EDs should be agreed and implemented at EU level. It was pointed out, however, that individual 
Member  State  actions  are  justified  in  case  of  sound  scientific  evidence  of  concern,  in  line  with  the 
precautionary principle, when follow-up action at EU level cannot be agreed in an appropriate time 
frame.  

Many stakeholders referred to past examples where individual MS-level actions have led to EU-level 
action, thus positively contributing to the protection goals and reduction of societal costs. To provide 
equal level of protection to all citizens in the EU and to preserve the single market, EU-level actions 
should follow in a timely manner.  

Some  stakeholders  proposed  to  introduce  legal  mechanisms  that  automatically  trigger  a  follow-up 
assessment  centrally  at  EU-body-level  in  case  relevant  actions  are  taken  at  the  level  of  Member 
States. 
*Respondents  to  all  three  surveys  (citizens,  stakeholder  and  SME  surveys)  were  self-selected  and  thus  not 
necessarily representative of the full range of views of these groups. 

105 

 
 
 
 
 
 
 
 
 
 
 
9  CONCLUSIONS 

Endocrine disruptors (EDs) are chemical substances of synthetic or natural origin that adversely affect 
the  health  of  humans  and  animals  by  altering  the  functioning  of  the  endocrine  system.  Exposure  to 
EDs  can  occur  from  different  sources,  such  as  pesticide  residues  in  food  or  everyday  consumer 
products. Different regulatory approaches for managing the risks posed by EDs exist because sector-
specific  regulations  have  been  developed  at  different  points  in  time  and  in  some  cases  incorporate 
different specific considerations. This raises questions about the overall coherence of the EU’s legal 
framework in relation to EDs.  

In this Fitness Check, the current ED-relevant provisions have been mapped across the EU Chemicals 
Acquis,  and  the  overall  regulatory  framework  has  been  analysed  in  terms  of  its  coherence, 
effectiveness, efficiency, relevance and EU-added value. 

Knowledge about endocrine disruptors 

Significant progress has been made in understanding EDs since the adoption of the 1999 Community 
Strategy  for  Endocrine  Disruptors.  Much  of  this  knowledge  relates  to  chemicals  that  affect  the 
estrogen,  androgen  or  thyroid  axes  or  that  interfere  with  steroidogenesis.  The  need  to  elucidate 
additional  mechanisms  of  endocrine  disruption  is  being  addressed  via  EU-funded  research  projects, 
such as those in the EURION cluster. 

The next generation of EU funded research will aim to address realistic mixture (combined) exposure 
scenarios  and  to  embrace  the  multi-factorial  nature  of  certain  indicators  of  concern,  such  as  the 
increase  in  certain  non-communicable  diseases  and  the  decline  in  biodiversity.  Building  on  the 
currently  available  methods  developed  in  key  research  areas  (e.g.  use  and  interpretation  of  human 
biomonitoring  data  and  effect-based  methods  in  water  quality  assessments)  the  Commission  is 
exploring  new  mechanisms  to  use  emerging  knowledge  in  the  policy  cycle  (e.g.  the  candidate 
European Partnership for Chemicals Risk Assessment). 

There is also a need to share information on chemicals  with all stakeholders, preferably via an open 
platform.  

Coherence 

The  coherence  of  the  regulatory  framework  was  assessed  by  focusing  on  the  definition  for  EDs, 
information  requirements,  hazard  and  risk  assessment  practices,  and  consequences  for  risk 
management.  

The  World  Health  Organization  definition  of  endocrine  disruptors  is  broadly  accepted  in  EU 
legislation. The criteria for the identification of EDs under the Plant Protection Products Regulation 
and Biocidal Products Regulation, and as substances of very high concern under REACH, are based 
on  this  definition.  EU  Agencies  (EFSA,  ECHA)  and  the  Commission’s  Scientific  Committee  on 
Consumer  Safety  (SCCS)  have  endorsed  the  definition  and  apply  it  in  their  assessments.    Cross-
sectorial (horizontal) criteria for EDs in EU legislation would facilitate consistent identification across 
sectors. 

Based  on  the  limited  number  of  chemicals  examined  for  endocrine  disrupting  properties  (mainly 
under the BPR or PPPR, and REACH), this Fitness Check did not identify any  cases of inconsistent 
identification. 

However,  the  current  data  requirements  limit  the  opportunity  to  identify  EDs.  The  update  of  data 
requirements to include further tests relevant for the detection of ED properties has started under the 
Biocidal and Plant Protection Products Regulations, as well as REACH. 

106 

 
 
EU  agencies  have  been  stepping  up  their  efforts  to  coordinate  assessment  work,  with  a  view  to 
ensuring  consistency  as  well  as  increased  efficiency  in  the  assessment  process.  These  efforts  will 
continue, as the European Green Deal commits the Commission to “review how to use better the EU’s 
agencies and scientific bodies to move towards a process of ‘one substance – one assessment’ and to 
provide greater transparency when prioritising action to deal with chemicals.”108  

There are only a few examples of risk assessments based on endocrine disrupting properties. In this 
limited number of cases, risks were identified following the standard risk assessment approach based 
on exceedance of a safe threshold (derived no-effect levels) for endpoints which were not necessarily 
ED-specific.  The  uncertainties  associated  with  the  possible  peculiarities  of  endocrine  disrupting 
effects  (i.e.  non-threshold,  non-monotonic  behaviour)  are  recognised  and  in  some  cases  have  been 
taken into account through the use of uncertainty factors defined on a case by case basis. 

Not  all  pieces  of  legislation  have  information  requirements  for  the  toxicological  properties  of 
chemicals, and nor do they need to, provided that mechanisms are in place to exploit data generated 
under other pieces of legislation. Differences in data requirements for the identification of EDs exist 
across different sectors, reflecting differing intended uses and exposure scenarios contributing to the 
risk,  as  well  as  the  need  to  consider  proportionality  with  respect  to  socioeconomic  and  laboratory 
animal welfare considerations. Where information requirements do exist, they need to be updated to 
include the latest validated methods relevant to ED identification.  

Information requirements also need to address the effects of chemicals on vulnerable groups. In this 
respect, there is an opportunity to introduce and improve the consistency of definitions of vulnerable 
groups  across  legislation,  and  to  clarify the  scientific  rationale  for  triggering  specific  provisions  for 
vulnerable groups (such as the unborn, children and the elderly). 

Across  the  chemicals  acquis,  the  co-legislators  have  opted  for  different  approaches  to  risk 
management  (namely,  generic  risk  approaches  vs  specific  risk  approaches  vs  risk/impact-benefit-
based)  according  to  specific  policy  considerations.  This  situation  has  been  criticised  by  many 
stakeholders,  who  expressed  concerns  that  differences  in  risk  management  measures  may  not  be 
justified. Indeed, the rationale for some of the differences should be made more transparent. A case in 
point concerns the possibilities for derogation from the exclusion or cut-off criteria for biocidal and 
plant protection products, respectively. Under BPR, a derogation can be  granted based on negligible 
risk,  essentiality  or  risk-benefit  considerations,  while  under  the  PPPR,  it  can  only  be  granted  when 
exposure is negligible or for essential uses.  

Despite differences in risk management approaches, this Fitness Check found no cases of inconsistent 
risk  management  for  specific  substances  based  on  the  lack  of  a  horizontal  approach  to  ED 
identification or any other ED-specific considerations. This finding has to be qualified, however, by 
the limited number of EDs risk managed due to their ED properties as examined in this Fitness Check. 

The difficulty in deciding between the generic risk approach and the specific risk approach is partly 
related to a fundamental scientific uncertainty – whether the effects of an ED are considered to have a 
threshold or not. In the absence of scientific consensus, legislation can either opt for an approach that 
does  not  require  an  answer  to  the  question  (e.g. generic  risk  approach  with derogations  as  done  for 
plant protection products and biocidal products) or it can determine case by case whether or not a safe 
(or acceptable) threshold can be quantified and consequently apply an appropriate risk management 
approach,  as  done  in  REACH.  In  certain  pieces  of  sectorial  legislation  (e.g.  Cosmetic  Products 

108COM(2019) 640  

107 

 
 
 
                                                      
Regulation,  Food  Contact  Materials  Regulation),  existing  guidance  and  examples  do  not  as  yet 
provide a clear indication about how to deal with EDs, for which it is not possible to quantify a safe 
(or acceptable) threshold. In practice, in cases where a threshold cannot be established, the regulatory 
approach  followed  under  EU  legislation  is  to  minimise  exposure  as  far  as  possible  including  the 
option to prohibit the use of a substance.  Application of the generic risk approach is combined with 
derogations allowing essential uses or risk-benefit options tailored to specific policy contexts. 

In  view  of  the  Commission’s  ambition  to  develop  a  process  of  “one  substance-one  assessment”, 
including a horizontal approach to EDs, consolidation and simplification options should be explored, 
as  well  as  better  communication  of  the  approach  to  citizens  and  stakeholders.  This  ambition  would 
also provide an opportunity to systematically assess and manage the risks resulting from the aggregate 
exposure to the same ED across sectors and from the combined exposures to different EDs, which is a 
concern  expressed  by  stakeholders.  A  “one  substance-one  assessment”  approach  was  seen  by  many 
stakeholders  as  a  way  of  avoiding  discrepancies  in  ED  identification  while  also  increasing  the 
effectiveness of regulatory procedures and improving communication with citizens. 

The  principle  of  a horizontal  approach to  ED  identification  and  assessment  is  broadly  supported  by 
stakeholders. However, it needs to be better defined what this means in practice. Elements to consider 
are: a) the common criteria for ED identification, based on the International Programme on Chemical 
Safety/World  Health  Organization  definition,  which  may  be  implemented  via  the  CLP  Regulation 
(and  GHS  at  the  international  level);  b)  a  common  basic  set  of  information  requirements,  including 
screening level information based on new approach methodologies, that provide the basis for applying 
the  criteria;  c)  a  common  toolbox  to  fulfil  the  information  requirements;  d)  guidance  on  the 
application of the toolbox and interpretation of the data generated; and e) a coordinated approach to 
ED  identification  and  risk  assessment,  including  whether  an  existing  piece  of  legislation,  such  as 
REACH, should serve as the basis for filling data gaps, where necessary.  

The International Programme on Chemical Safety/World Health Organization definition of endocrine 
disruptors  is  broadly  accepted  in  the  implementation  of  EU  legislation.  However,  in  view  of  the 
Commission’s ambition to develop a horizontal approach to ED identification, there will be a need to 
provide practical guidance on how this definition should be interpreted. A particular question will be 
whether  evidence  of  an  adverse  effect  can  only  be  based  on  the  observation  of  effects  in  living 
animals, or whether adversity can be concluded on the basis of scientific reasoning and extrapolation 
from  the  results  of  new  approach  methodologies  that  avoid  the  need  for  animal  testing.  This  has 
implications  not  only  for  effectiveness  (most  available  animal  tests  listed  under  legislative  data 
requirements  have  not  been  specifically  designed  to  detect  endocrine  effects),  but  also  coherence 
(animal testing  for all endpoints, including endocrine-related ones, is banned for cosmetic products, 
but not under other legislation) and efficiency (animal testing is costly, time-consuming and ethically 
questionable).  

Effectiveness 

Increasing trends in some adverse health and environmental impacts associated with EDs are a matter 
of societal concern. In this Fitness Check, however, it was not possible to draw firm conclusions on 
the effectiveness of EU legislation in reducing the potential impact of EDs on these trends.   

The  assessment  of  effectiveness  is  very  challenging,  mainly  because  of  the  attribution  challenge. 
Since there are multiple causes of these effects, it is difficult to determine to what extent exposure to 
EDs  contributes  to  the  observed  adverse  effects.  A  further  complication  is  that  observable  adverse 
effects on human health and the environment often do not materialise immediately after exposure. In 
particular, the effects of early life exposure to EDs may not materialise until many years later.  

108 

 
 
Nevertheless,  for  some  EDs,  environmental  monitoring  data  and/or  human  biomonitoring  data  have 
provided evidence that restriction measures (although taken in relation to other hazardous properties) 
have been successful in reducing exposure levels. There are examples of non-approval of substances 
with  endocrine  disrupting  properties  resulting  in  significant  benefits  to  wildlife.  For  instance, 
international bans on the use of the endocrine disruptor tributyltin as an antifoulant in marine paints 
has resulted in the recovery of mollusc populations in European coastal waters.  

The methodological challenges in assessing effectiveness point to a need to develop and apply a more 
extensive suite of indicators. 

It  is  too  early  to  assess  the  effectiveness  of  the  BPR  and  PPPR,  since  only  a  limited  number  of 
substances have been identified as EDs or as not being EDs, according to the criteria adopted in 2018. 
Reflecting the need to gain experience, the Regulations setting out the criteria foresee a review after 7 
years, i.e. by 2025. 

Under REACH, 17 substances have been identified as Substances of Very High Concern (SVHC) due 
to  endocrine  disrupting  properties  with  respect  to  human  health  and/or  the  environment.  However, 
only  octylphenol,  nonylphenol  and  their  ethoxylates  are  subject  to  authorisation  specifically  due  to 
their  endocrine  disrupting  properties.  The  inclusion  of  a  substance  in  the  Candidate  List  for 
authorisation  due  to  concerns  for  endocrine  disrupting  effects  triggers  additional  provisions  for  risk 
assessment (Chemical Safety Report) and risk communication (Safety Data Sheet).  

CMRs cat. 1A/1B can be identified as SVHCs under REACH and fulfil the cut-off/exclusion criteria 
for non-approval under the plant protection products and biocidal products regulations. Identification 
of  a  CMR  as  an  ED  for  human  health  will  probably  not  lead  to  any  additional  risk  management 
measures,  where  they  are  already  the  strictest,  but  may  nevertheless  contribute  to  the  overall 
evaluation within a risk-benefit context. 

CMR classification is not, however, sufficient to capture all EDs for human health, since other effects 
are potentially mediated by endocrine disruption, such as certain neurodevelopmental and metabolic 
disorders.  As  methods  for  less  studied  modalities  of  endocrine  disruption  become  available,  it  is 
expected that more substances will be identified as EDs beyond CMRs. 

Data requirements for the identification of EDs are being updated under the PPPR, BPR and REACH 
to include already existing OECD test guidelines relevant to ED assessment, in particular to include 
the so-called ‘mechanistic’ tests, which can pinpoint a specific endocrine modality.  

Some pieces of sectorial legislation rely primarily on REACH for ED identification. Others such as 
food contact materials, food additives and cosmetic products have further requirements for products 
or sectors they regulate but these do not, as yet, specifically address endocrine disruption. Due to the 
animal testing ban in the cosmetics sector, a specific issue arises concerning the identification of EDs 
given the need to demonstrate an adverse effect in intact organisms, which currently requires in vivo 
testing. 

There  may  be  a  need  to  strengthen  the  interconnections  between  legislation,  such  as  REACH,  that 
have provisions for data generation with sector and product-specific legislation that rely on such data 
for assessment and management purposes. This may require that ED risk management provisions are 
introduced  into  certain  pieces  of  legislation,  which  currently  do  not  contain  any  reference  to  EDs, 
respecting  the  special  case  of  cosmetics  where  in  vivo  tests  should  not  be  generated  solely  for  the 
purposes of cosmetic ingredient evaluation. Effective sharing of data across legislation should ensure 
that the information eventually generated is made available for assessing potential EDs falling under 
sectorial legislation where information is not specifically required. 

109 

 
 
Irrespective of regulatory provisions for identifying EDs, there is a technical challenge concerning the 
ability  to  identify  EDs.  While  progress  has  been  made  in  developing  standardised  test  methods  for 
identifying EDs and characterising their hazards, the current assessment toolbox is still mainly based 
on animal tests. The toolbox is incomplete in terms of its coverage of all adverse outcomes and is also 
limited to a few modes of endocrine action. Another limitation is the ability to detect possible effects 
of EDs in sensitive life stages. The involvement of the endocrine system in the control of processes 
such as embryonic development and puberty means that foetuses, infants and adolescents are at higher 
risk regarding endocrine disruption.  

Given the limitations of the current assessment toolbox, new approach methodologies, not involving 
the use of animals, need to be developed and integrated into the regulatory assessment process. The 
Commission  is  addressing  this  challenge  on  multiple  fronts,  from  funding  research  into  the 
development of new methods, to assessing their scientific validity, to promoting their adoption (once 
validated) as OECD Test Guidelines. 

Communication on the presence of EDs in products (articles and mixtures) is required under REACH 
(when  identified  as  SVHCs)  and  the  BPR.  However,  there  is  scope  to  improve  the  availability  of 
information on EDs across sectors. 

Efficiency 

Inefficiencies  in  the  assessment  and  management  of  endocrine  disruptors  can  result  from  situations 
where a given substance falls within the mandate of multiple agencies and scientific committees, but 
also  from  certain  regulatory  provisions,  such  as  “equivalent  level  of  concern”  under  REACH.  EU 
agencies  have  been  stepping  up  their  efforts  to  coordinate  assessment  work.  However,  efficiencies 
could be gained by developing a horizontal approach to EDs, including an increased use of grouping 
approaches and new approach methodologies that avoid the use of animal tests.  

The need to carry out testing and assessment for additional ED-related effects for a larger number of 
chemicals  will  inevitably  lead  to  increased  workload  and  costs.  Some  industry  stakeholders  are 
concerned that this will put economic operators in the EU at a competitive disadvantage, while some 
public authority stakeholders are concerned that this will result in delays to other areas of regulatory 
assessment work.  

The costs and benefits for human health and the environment resulting from regulatory requirements 
to assess and manage risks of chemicals, including endocrine disruptors, are difficult to quantify and 
compare.  There  is  a  need  to  further  develop  and  harmonise  risk-benefit  methodologies,  such  as 
socioeconomic  analysis.  In  this  Fitness  Check,  two  case  studies  illustrated  the  methodological 
challenges  in  performing  conclusive  macroeconomic  assessments  on  the  possible  impacts  of 
regulatory interventions on trade. This is partly because there is a lack of trade flow data at the level 
of specific chemicals and the commodities containing these chemicals, as well as data on the market 
share of a chemical in a given commodity. 

EU-added value 

Regulating  EDs  at  EU  level  contributes  to  ensuring  an  equal  level  of  protection  across  the  EU 
Member States regarding human and environmental health. The need for the EU to act in this area is 
broadly supported by the public and stakeholders, and at the political level by EU institutions such as 
European Parliament and the EU Committee of the Regions. 

There  is  an  opportunity  for  the  Member  States  to  join  forces  in  testing  capacities,  experience  and 
knowledge sharing. This should lead to greater efficiency and scientific consistency in the assessment 

110 

 
 
of  EDs.  A  uniform  EU  approach  also  strengthens  the  EU’s  position  in  chemicals  regulation 
worldwide, which also has benefits for the EU chemical industry. 

Safeguard  clauses  in  EU  legislation  allow  unilateral  risk  management  measures  to  be  taken  at 
Member State level, in cases where an individual Member State has concerns regarding human health 
or the environment.  Such measures have been  taken  for a few ED substances,  such as Bisphenol A 
and DEHP, and are usually followed by EU-level intervention or withdrawal of unilateral action, to 
ensure an equal level of protection throughout the EU. 

Relevance 

Societal  concerns  about  the  health  and  environmental  impacts  of  EDs  are  high,  consistent  with 
concerns about chemicals in general. Perspectives on the importance of regulating EDs are polarised 
between different stakeholder groups. Citizens engaged in the topic generally lack trust in the ability 
of  EU  legislation  to  achieve  its  objectives  of  human  health  and  environmental  protection,  while 
economic  stakeholders  are  concerned  that  decisions  may  ultimately  be  based  on  societal  concerns 
rather than science-based evidence. 

A  particular  challenge  over  the  coming  decades  is  the  expected  global  trend  towards  increased 
chemical manufacturing outside the EU, primarily in Asia. The successful implementation of the EU 
Circular  Economy  Action  Plan  will  promote  innovation  and  give  proper  incentives  to  chemical 
suppliers, wherever they are located, as regards the safe use and life cycle management of chemicals. 

Overall conclusions  

The need to address the impacts of EDs on human health and the environment is highly relevant to 
EU citizens, who also favour regulatory action at the EU level.  

Based on the limited number of chemicals examined for ED properties under the BPR or PPPR, or as 
SVHCs  with  ED  properties  under  REACH,  this  Fitness  Check  did  not  identify  any  cases  of 
inconsistent  identification  across  sectors.  However,  the  need  for  a  horizontal  approach  for 
identification  of  EDs  has  been  recognised  that  is  based  on  the  definition  of  the  World  Health 
Organization and builds on the criteria developed for plant protection products and biocidal products 
while ensuring that it is fit for purpose for other relevant legislation, particularly for REACH but also 
legislation  on  cosmetic  products,  toys  and  food  contact  materials.  This  is  also  an  opportunity  to 
simplify and rationalise current parallel identification procedures.  

A horizontal approach for the identification of EDs would also feed into the development of a ‘one 
substance-one  assessment’  approach  across  legislation  and  facilitate  the  management  of  risks  to 
humans  and  wildlife  resulting  from  combined  exposures  to  different  endocrine  disruptors  regulated 
under different pieces of legislation. Current data requirements limit the opportunity to identify EDs. 
The  strengthening  of  information  requirements  in  the  relevant  legislation  is  key  to  improving  the 
identification of EDs.  

This  Fitness  Check  could  not  conclude  on  the  effectiveness  of  the  chemicals  acquis  in  protecting 
health and the environment from EDs. However, there is a need to explore options to strengthen the 
legislative  framework  to  further  minimise  exposure  to  EDs,  both  for  consumers  and  for  the 
environment 

Overall,  there  are  opportunities  for  simplification,  consolidation,  burden  reduction  and  better 
communication of the principles guiding risk management of EDs. The findings of this Fitness Check 
will provide an input to the Chemicals Strategy for Sustainability being developed in the context of 
the European Green Deal. 

111 

 
 
10 REFERENCES 
Baken,  K.A.,  Lambrechts,  N.,  Remy,  S.,  Mustieles,  V.,  Rodríguez-Carrillo,  A.,  Neophytou,  C.M., 
Olea,  N.,  and  Schoeters,  G.  (2019).  A  strategy  to  validate  a  selection  of  human  effect  biomarkers 
using  adverse  outcome  pathways:  Proof  of  concept  for  phthalates  and  reproductive  effects.  Environ 
Res 175, 235-256. 

Bellanger, M., Demeneix, B., Grandjean, P., Zoeller, R.T., and Trasande, L. (2015). Neurobehavioral 
deficits, diseases, and associated costs of exposure to endocrine-disrupting chemicals in the European 
Union. J Clin Endocrinol Metab 100, 1256-1266. 

Bolt,  H.M.  (2017).  The  current  debate  on  cost  burden  by  human  exposure  to  endocrine  disrupting 
chemicals. Arch Toxicol 91, 2965-2966. 

Bond, G.G., and Dietrich, D.R. (2017a). Further thoughts on limitations, uncertainties and competing 
interpretations regarding chemical exposures and diabetes. J Epidemiol Community Health 71, 943. 

Bond,  G.G.,  and  Dietrich,  D.R.  (2017b).  Human  cost  burden  of  exposure  to  endocrine  disrupting 
chemicals. A critical review. Arch Toxicol 91, 2745-2762. 

Bopp, S.K., Kienzler, A., Richarz, A.N., van der Linden, S.C., Paini, A., Parissis, N., and Worth, A.P. 
(2019).  Regulatory  assessment  and  risk  management  of  chemical  mixtures:  challenges  and  ways 
forward. Crit Rev Toxicol 49, 174-189. 

Brack, W., Dulio, V., Ågerstrand, M., Allan, I., Altenburger, R., Brinkmann, M., Bunke, D., Burgess, 
R.M.,  Cousins,  I.,  Escher,  B.I.,  et  al.  (2017).  Towards  the  review  of  the  European  Union  Water 
Framework Directive: Recommendations for more efficient assessment and management of chemical 
contamination in European surface water resources. Sci Total Environ 576, 720-737. 

Browne, P., Van Der Wal, L., and Gourmelon, A. (2020). OECD approaches and considerations for 
regulatory evaluation of endocrine disruptors. Mol Cell Endocrinol 504, 110675. 

Brunel  University  London,  and  DTU  Food  National  Food  Institute  Denmark  (2016).  Mapping 
commonalities  and  differences  in  approaches  for  testing  and  assessment  of  endocrine  disruptors 
within the EU and among relevant international trading partners (https://op.europa.eu/en/publication-
detail/-/publication/0abd23e0-ec38-11e6-ad7c-01aa75ed71a1). 

Canzian,  G.,  Giua,  L.,  and  Verzillo,  S.  (2020).  Impact  of  interventions  regulating  Endocrine 
Disruptors 
JRC120335. 
https://publications.jrc.ec.europa.eu/repository/handle/JRC120335 

dynamics 

Member 

States. 

trade 

EU 

for 

on 

Chemsec (2019). Lost at SEA-The information policymakers actually need from applicants and SEAC 
opinions (https://chemsec.org/publication/authorisation-process,reach/lost-at-sea/). 

Demeneix,  B.,  and  Slama,  R.  (2019).  Endocrine  Disruptors:  from  Scientific  Evidence  to  Human 
HealthProtection (doi: 10.2861/802173 | QA-01-19-272-EN-N ). 

ECHA (2011). Guidance on the preparation of socio-economic analysis as part of an application for 
authorisation  (https://echa.europa.eu/documents/10162/23036412/sea_authorisation_en.pdf/aadf96ec-
fbfa-4bc7-9740-a3f6ceb68e6e). 

112 

 
 
ECHA RAC 2017. Risk-related considerations in applications for authorisation for endocrine 
disrupting substances for the environment, specifically OPnEO and NPnEO. 
https://echa.europa.eu/documents/10162/13637/npneo_and_opneo_for_agreement_final_en.pdf/ 

ECHA (2020). The use of bisphenol A and its alternatives in thermal paper in the EUduring 2014  -
2022 
(https://echa.europa.eu/documents/10162/23294236/bpa_thermal_paper_report_2020_en.pdf/59eca26
9-c788-7942-5c17-3bd822d9cba0). 

ECHA, EFSA, and JRC (2018). Guidance for the identification of endocrine disruptors in the context 
of Regulations (EU) No 528/2012 and (EC) No 1107/2009. EFSA Journal, 16, 5311. 

Ecorys  (2018).  Study  supporting  the  REFIT  Evaluation  of  the  EU  legislation  on  plant  protection 
products and pesticides residues (Regulation (EC) No 1107/2009 and Regulation (EC) No 396/2005) 
(doi: 10.2875/88433). 

ECPI (2014). Denmark scraps plan to ban four phthalate plasticizers. Additives for Polymers 9, 11. 

EFSA  (2020a).  Cumulative  dietary  risk  characterisation  of  pesticides  that  have  acute  effects  on  the 
nervous system. EFSA Journal, 18, 6087. 

EFSA (2020b). Cumulative dietary risk characterisation of pesticides that have chronic effects on the 
thyroid. EFSA Journal, 18, 6088. 

EFSA Panel on Food Additives and Nutrient Sources added to Food (2012). Guidance for submission 
for food additive evaluations. EFSA Journal, 10, 2760. 

EFSA Panel on Food Contact Materials, Enzymes, and Flavourings and Processing Aids (2008). Note 
for  Guidance  for  the  Preparation  of  an  Application  for  the  Safety  Assessment  of  a  Substance  to  be 
used in Plastic Food Contact Materials. EFSA Journal, 6, 21r. 

EFSA  Panel  on  Food  Contact  Materials,  Enzymes,  and  Flavourings  and  Processing  Aids  (2015). 
Scientific  Opinion  on  the  risks  to  public  health  related  to  the  presence  of  bisphenol  A  (BPA)  in 
foodstuffs. EFSA Journal, 13, 3978. 

EFSA  Panel  on  Food  Contact  Materials,  Enzymes,  and  Flavourings  and  Processing  Aids  (2016). 
Recent  developments  in  the  risk  assessment  of  chemicals  in  food  and  their  potential  impact  on  the 
safety assessment of substances used in food contact materials. EFSA Journal, 14, 4357. 

EFSA  Scientific  Committee  (2013).  Scientific  Opinion  on  the  hazard  assessment  of  endocrine 
disruptors: Scientific criteria for identification of endocrine disruptors and appropriateness of existing 
test methods for assessing effects mediated by these substances on human health and the environment. 
EFSA Journal, 11, 3132. 

EMA  (2000).  GL6  Environmental  impact  assessment  (EIAS)  for  veterinary  medicinal  products  - 
Phase  I  (https://www.ema.europa.eu/en/vich-gl6-environmental-impact-assessment-eias-veterinary-
medicinal-products-phase-i#current-effective-version-section). 

113 

 
 
 
EMA (2005). GL38 Environmental impact assessments for veterinary medicinal products  - Phase II 
(GL38  Environmental 
impact  assessments  for  veterinary  medicinal  products  -  Phase  II 
(CVMP/VICH/790/2003)). 

European  Commission  (2014).  Technical  Report  on  Aquatic  Effect-Based  Monitoring  Tools  (doi: 
10.2779/7260). 

European  Commission  (2015).  Report  on  Public  consultation  on  defining  criteria  for  identifying 
endocrine disruptors in the context of the implementation of the Plant Protection Product Regulation 
and 
Regulation 
(https://ec.europa.eu/health/sites/health/files/endocrine_disruptors/docs/2015_public_consultation_rep
ort_en.pdf). 

Products 

Biocidal 

Fraunhofer-Institut  (1999).  Revised  Proposal  for  a  List  of  Priority  Substances  in  the  Context  of  the 
Water 
(https://ec.europa.eu/environment/water/water-
dangersub/pdf/commps_report.pdf). 

Framework 

Directive 

Ganzleben, C., Antignac, J.P., Barouki, R., Castaño, A., Fiddicke, U., Klánová, J., Lebret,  E., Olea, 
N.,  Sarigiannis,  D.,  Schoeters,  G.R.,  et  al.  (2017).  Human  biomonitoring  as  a  tool  to  support 
chemicals regulation in the European Union. Int J Hyg Environ Health 220, 94-97. 

Gennings, C., Shu, H., Rudén, C., Öberg, M., Lindh, C., Kiviranta, H.,  and Bornehag, C.G. (2018). 
Incorporating regulatory guideline values in analysis of epidemiology data. Environ Int 120, 535-543. 

Gore, A.C., Chappell, V.A., Fenton, S.E., Flaws, J.A., Nadal, A., Prins, G.S., Toppari, J., and Zoeller, 
R.T. (2015). EDC-2: The Endocrine Society's Second  Scientific Statement on Endocrine-Disrupting 
Chemicals. Endocr Rev 36, E1-e150. 

Hamers,  T.,  Kortenkamp,  A.,  Scholze,  M.,  Molenaar,  D.,  Cenijn,  P.H.,  and  Weiss,  J.M.  (2020). 
Transthyretin-Binding  Activity  of  Complex  Mixtures  Representing  the  Composition  of  Thyroid-
Hormone Disrupting Contaminants in House Dust and Human Serum.  Environ Health Perspect 128, 
17015. 

Hamers, T., Legradi, J., Zwart, N., Smedes, F., de Weert, J., van den Brandhof, E.J., van de Meent, 
D.,  and  de  Zwart,  D.  (2018).  Time-Integrative  Passive  sampling  combined  with  TOxicity  Profiling 
(TIPTOP):  an  effect-based  strategy  for  cost-effective  chemical  water  quality  assessment.  Environ 
Toxicol Pharmacol 64, 48-59. 

Hauser,  R.,  Skakkebaek,  N.E.,  Hass,  U.,  Toppari,  J.,  Juul,  A.,  Andersson,  A.M.,  Kortenkamp,  A., 
Heindel, J.J., and Trasande, L. (2015). Male reproductive disorders, diseases, and costs of exposure to 
endocrine-disrupting chemicals in the European Union. J Clin Endocrinol Metab 100, 1267-1277. 

IPCS (2002). Global Assessment of the State-of_the-Science of Endocrine Disruptors, T. Damstra, S. 
Barlow, 
eds. 
(https://www.who.int/ipcs/publications/new_issues/endocrine_disruptors/en/). 

Bergman, 

Kavlock, 

Kraak, 

Van 

Der 

and 

G. 

A. 

R. 

Lee,  J.E.,  Jung,  H.W.,  Lee,  Y.J.,  and  Lee,  Y.A.  (2019).  Early-life  exposure  to  endocrine-disrupting 
chemicals and pubertal development in girls. Ann Pediatr Endocrinol Metab 24, 78-91. 

114 

 
 
Legler, J., Fletcher, T., Govarts, E., Porta, M., Blumberg, B., Heindel, J.J., and Trasande, L. (2015). 
Obesity, diabetes, and associated costs of exposure to endocrine-disrupting chemicals in the European 
Union. J Clin Endocrinol Metab 100, 1278-1288. 

Lucaccioni, L., Trevisani, V., Marrozzini, L., Bertoncelli, N., Predieri, B., Lugli, L., Berardi, A., and 
Iughetti,  L.  (2020).  Endocrine-Disrupting  Chemicals  and  Their  Effects  during  Female  Puberty:  A 
Review of Current Evidence. Int J Mol Sci 21. 

Middelbeek,  R.J.,  and  Veuger,  S.A.  (2015).  Letter  to  the  Editor:  Re:  Neurobehavioral  Deficits, 
Diseases,  and  Associated  Costs  of  Exposure  to  Endocrine-Disrupting  Chemicals  in  the  European 
Union. J Clin Endocrinol Metab 100, L52-53. 

Milieu Ltd, Ökopol, Risk & Policy Analysts, and RIVM (2017). Study for the strategy for a non-toxic 
environment 
Programme 
(https://ec.europa.eu/environment/chemicals/non-toxic/pdf/NTE%20main%20report%20final.pdf). 

Environment 

Action 

7th 

the 

of 

Ministère de la Transition Ecilogique et Solidaire, M.d.S.e.d.l.S. (2019). Second National strategy on 
endocrine 
(https://www.ecologique-
solidaire.gouv.fr/sites/default/files/SNPE%202%20english%20-%20Action%20plan.pdf). 

disruptors 

Munn,  S.,  and  Goumenou,  M.  (2013a).  Key  scientific  issues  relevant  to  the  identification  and 
characterisation of endocrine disrupting substances. 

Munn,  S.,  and  Goumenou,  M.  (2013b).  Thresholds  for  Endocrine  Disrupters  and  Related 
Uncertainties. 

OECD  (2017).  New  Scoping  Document  on  in  vitro  and  ex  vivo  Assays  for  the  Identification  of 
Modulators of Thyroid Hormone Signalling (https://doi.org/10.1787/9789264274716-en). 

OECD  (2018).  Revised  Guidance  Document  150  on  Standardised  Test  Guidelines  for  Evaluating 
Chemicals for Endocrine Disruption (https://doi.org/10.1787/9789264304741-en). 

OECD  (2019).  Considerations  when  Assessing  Children's  Exposure  to  Chemicals  from  Products 
(http://www.oecd.org/officialdocuments/publicdisplaydocumentpdf/?cote=ENV/JM/MONO(2019)29
&docLanguage=en). 

Olsson, I.-M., and al., e. (2014). The cost of inaction  - A Socioeconomic analysis of costs linked to 
effects 
health 
(http://dx.doi.org/10.6027/TN2014-557). 

reproductive 

substances 

disrupting 

endocrine 

male 

on 

of 

Petrakis, D., Vassilopoulou, L., Mamoulakis, C., Psycharakis, C., Anifantaki, A., Sifakis, S., Docea, 
A.O., Tsiaoussis, J., Makrigiannakis, A., and Tsatsakis, A.M. (2017). Endocrine Disruptors Leading 
to Obesity and Related Diseases. Int J Environ Res Public Health 14. 

Posthuma, L., Dyer, S.D., de Zwart, D., Kapo, K., Holmes, C.M., and Burton, G.A., Jr. (2016). Eco-
epidemiology of aquatic ecosystems: Separating chemicals from multiple stressors. Sci Total Environ 
573, 1303-1319. 

Risk  &  Policy  Analysts  Limited  (2015).  Analysis  of  capacities  and  capabilities  of  laboratories 
toconduct  OECD  TG  443  extended  one-generationreproductive  toxicity  study  (OECD  TG  443) 
(https://echa.europa.eu/documents/10162/13630/echa_sr26_eogrts_en.pdf). 

115 

 
 
Rogiers et al (2020). The way forward for assessing the human health safety of cosmetics in the EU - 
Workshop proceedings, Toxicology 436. https://doi.org/10.1016/j.tox.2020.152421 

SCCS  (2018).  SCCS  Notes  of  Guidance  on  for  the  testing  of  cosmetic  ingredients  and  their  safety 
evaluation  (10th  revision)  (https://op.europa.eu/en/publication-detail/-/publication/1d5f1653-38ce-
11e9-8d04-01aa75ed71a1/language-en/format-PDF). 

Schug, T.T., Janesick, A., Blumberg, B., and Heindel, J.J. (2011). Endocrine disrupting chemicals and 
disease susceptibility. J Steroid Biochem Mol Biol 127, 204-215. 

Slama, R., Vernet, C., Nassan, F.L., Hauser, R., and Philippat, C. (2017). Characterizing the effect of 
endocrine disruptors on human health: The role of epidemiological cohorts. C R Biol 340, 421-431. 

Solecki,  R.,  Kortenkamp,  A.,  Bergman,  Å.,  Chahoud,  I.,  Degen,  G.H.,  Dietrich,  D.,  Greim,  H., 
Håkansson,  H.,  Hass,  U.,  Husoy,  T.,  et  al.  (2017).  Scientific  principles  for  the  identification  of 
endocrine-disrupting chemicals: a consensus statement. Arch Toxicol 91, 1001-1006. 

Tang, J.,  and Zhai, J.X. (2017). Distribution of polybrominated diphenyl ethers in breast  milk, cord 
blood and placentas: a systematic review. Environ Sci Pollut Res Int 24, 21548-21573. 

Trasande,  L.,  Zoeller,  R.T.,  Hass,  U.,  Kortenkamp,  A.,  Grandjean,  P.,  Myers,  J.P.,  DiGangi,  J., 
Bellanger, M., Hauser, R., Legler, J., et al. (2015). Estimating burden and disease costs of exposure to 
endocrine-disrupting chemicals in the European union. J Clin Endocrinol Metab 100, 1245-1255. 

UNEP (2019). Global Chemicals Outlook IIFrom Legacies to Innovative Solutions: Implementing the 
2030 
Report 
(https://wedocs.unep.org/bitstream/handle/20.500.11822/27651/GCOII_synth.pdf?sequence=1&isAll
owed=y). 

Development 

Sustainable 

Synthesis 

Agenda 

for 

– 

UNEP  IPCP  (2017).  Worldwide  initiatives  to  identify  endocrine  disrupting  chemicals  (EDCs)  and 
EDCs 
potential 
(http://wedocs.unep.org/bitstream/handle/20.500.11822/25633/EDC_report1.pdf?sequence=1&isAllo
wed=y). 

WHO/UNEP 
(https://www.who.int/ceh/publications/endocrine/en/). 

(2012).  State  of 

the  science  of  endocrine  disrupting  chemicals 

-  2012 

116 

 
 
 
 
 
11 GLOSSARY 

Term  

Adverse effect 

Adverse Outcome Pathway (AOP) 

Alternative method 

Apical Endpoint 

Biomarker 

Dose-response relationship  

EATS parameters 

ED criteria 

Definition / Explanation 

in 

increase 

different 

responding 

to  multiple 

A  change 
the  morphology,  physiology,  growth, 
development,  reproduction,  or,  life  span  of  an  organism, 
system,  or  (sub)population  that  results  in  an  impairment  of 
functional  capacity,  an  impairment  of  the  capacity  to 
compensate 
in 
for  additional  stress,  or  an 
susceptibility to other influences.  
An AOP is an analytical construct that describes a sequential 
chain of causally linked events at different levels of biological 
organisation that lead to an adverse health or ecotoxicological 
effect.   
A method that replaces, reduces or refines the use of animals 
in toxicity testing 
An  observable  outcome  in  a  whole  organism,  such  as  a 
clinical  sign  or  pathological  state  that  is  indicative  of  a 
disease  state  that  can  result  from  exposure  to  a  toxicant.  As 
such,  the  apical  endpoint  is  representing  a  measurable 
outcome 
toxicity 
pathways/MoAs  and  can  potentially  be  indicative  of  adverse 
effects. 
A  biological  parameter  that  is  objectively  measured  and 
evaluated  as  an  indicator  of  normal  biological  state  or 
pathological processes. 
The  dose–response  relationship  describes  the  change  (in 
nature,  incidence,  magnitude  and/or  severity)  in  an  effect  on 
an organism caused by different levels of exposure (or doses) 
to  a  stressor  (usually  a  chemical)  after  certain  exposure 
duration. This definition includes the following assumptions: 
the  response  observed  is  due  to  the  chemical  administered, 
the  magnitude  of  the  response  is  in  fact  related  to  the  dose 
and the observed effect is quantifiable. 
Parameters  measured  in  vivo  that  may  contribute  to  the 
evaluation  of  adversity,  while  at  the  same  time  (due  to  the 
nature  of  the  effect  and  the  existing  knowledge  as  described 
in  OECD  GD  150)  they are  also  considered  indicative  of  an 
EATS  MoA  and  thus  (in  the  absence  of  other  explanations) 
also  imply  underlying  in  vivo  mechanistic  information.  This 
group 
from  OECD 
the  parameters  mainly 
Conceptual Framework Level 4 and 5 tests labelled in OECD 
GD  150  as  ‘endpoints  for  estrogen-mediated  activity’, 
‘endpoints  for  androgen-mediated  activity’,  ‘endpoints  for 
thyroid-related 
for 
steroidogenesis-related activity’. 
The  criteria  are  legally  defined  in  Commission  Delegated 
Regulation  (EU)  No  2017/2100  and  Commission  Regulation 
(EU) No 2018/605 for biocidal products and plant protection 
products,  respectively.  They  are  based  on 
the  2002 
WHO/IPCS definition of an endocrine disruptor. They ask for 
consideration,  in  a  weight  of  evidence  approach,  of  all 
relevant scientific information including human and/or animal 

‘endpoints 

activity’ 

includes 

and/or 

117 

 
 
 
 
Term  

Definition / Explanation 

Endocrine activity 

Endocrine disruptor 

Endocrine modality 

Endocrine system 

Group of substances 

Hormone 

In silico model 

In vitro test 

Integrated  Approach  to  Testing  and 
Assessment 

Mechanism of action 

Mode of action (MoA) 

in  an 

evidence,  therefore  allowing  for  the  identification  of  both 
known and presumed endocrine disrupting substances.  
Interaction  with  the  endocrine  system  that  can  potentially 
result in a response of the endocrine system, target organs and 
tissues.  A  substance  that  has  an  endocrine  activity  it  has  the 
potential to alter the function(s) of the endocrine system. 
An exogenous substance or  mixture that alters function(s) of 
the endocrine system and consequently causes adverse health 
effects 
its  progeny,  or 
intact  organism,  or 
(sub)populations.  
A  modality  is  an  axis,  pathway,  signalling  process,  in  this 
case within the endocrine system. 
The  endocrine  system  is  a  highly  integrated  and  widely 
distributed  group  of  organs  that  orchestrates  a  state  of 
metabolic  equilibrium,  or  homeostasis,  among  the  various 
organs  of  the  body.  In  endocrine  signalling,  molecules,  i.e. 
hormones, act on target cells that are separate from their site 
of synthesis.   
Substances  that  have  physicochemical,  toxicological  and 
ecotoxicological  properties  that  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.  
Substances  which  are  produced  by  endocrine  glands  and 
secreted  into  the  circulation,  and  which  exert  a  regulatory 
effect elsewhere in the body.  
The  technique  of  performing  experiments  via  computer 
simulations. 
Structure-Activity 
Relationships  (SAR)  and  Quantitative  Structure-Activity 
Relationships (QSAR).  
The  technique  of  performing  a  given  experiment  in  a  test 
tube, or, more generally, in a controlled environment outside 
of a living organism.  
A  structured  approach  used 
identification 
(potential),  hazard  characterisation  (potency)  and/or  safety 
assessment (potential/potency and exposure) of a chemical or 
group  of  chemicals,  which  strategically 
integrates  and 
weights  all  relevant  data  to  inform  regulatory  decision 
regarding  potential  hazard  and/or  risk  and/or  the  need  for 
further targeted and therefore minimal testing. 
A  detailed  molecular  description  of 
the  mechanistic 
interaction  through  which  a  substance/molecule  produces  its 
effect.   
A  biologically  plausible  sequence  of  key  events  at  different 
levels of biological organisation, starting with the exposure to 
a chemical and leading to an observed (adverse) effect. 

for  hazard 

Examples 

include 

New Approach Methodology (NAM)  A  recently  coined 

to  any 

technology, 
term  referring 
methodology  or  combination  thereof,  that  can  be  used  to 
provide  information  on  chemical  hazard  and  risk  assessment 
that avoids the use of intact animals. 
An  alternative  method  that  avoids  testing  in  intact  animals. 
The more traditional phrase for New Approach Methodology 
Uncertainty refers to all types of limitations in the knowledge 

118 

Non-animal method 

Uncertainty 

 
 
Term  

Definition / Explanation 

Weight of evidence (WoE) 

available to assessors at the time an assessment is conducted 
and within the time and resources agreed for the assessment.   
A  stepwise  process/approach  of  collecting  and  weighing 
evidence  to  reach  a  conclusion  on  a  particular  problem 
formulation including assessment of the degree of confidence. 

119 

 
 
 
 
 
Annex 1.  Procedural information 

1  Lead DG and internal references 
The  "Fitness  Check  on  the  relevant  EU  legislation  on  Endocrine  Disruptors"  was  led  by  DG  Joint 
Research  Centre  (JRC).  The  mandate  was  established  in  the  Communication  “Towards  a 
comprehensive European Union framework on endocrine disruptors”109.   

Issues relevant to endocrine disruptors (EDs) were included in recent Fitness Checks and evaluations 
of  chemical  legislation,  including  the  REACH  REFIT  evaluation,  the  REACH  Review  on  the 
authorisation  route  of  substances  with  endocrine  disrupting  properties  according  to  REACH  Art. 
138(7),  the  Fitness  Check  of  the  chemicals  legislation  other  than  REACH,  the  review  of  the 
legislation on cosmetics with regard to endocrine disrupting substances, and the evaluation of the 7th 
Environment  Action  Programme.  Among  legislation  regulating  downstream  uses  of  chemicals  in 
products,  the  evaluation  of  the  legislation  on  food  contact  materials  and  the  evaluation  of  the 
legislation  on  toy  safety  were  also  considered  relevant  to  this  FC.  Among  pieces  of  environmental 
legislation,  the  Fitness  Check  of  the  water  legislation  was  considered  for  potentially  ED-relevant 
aspects. 

Also relevant was Annex 9 of the impact assessment on the definition of criteria for identifying EDs 
in  the  context  of  the  Plant  Protection  Products  Regulation  and  Biocidal  Products  Regulation.  This 
provides a multi criteria analysis of impacts (on health, environment etc.) based on a scientific review 
of the evidence linking endocrine disrupting chemicals to hormone-related diseases and the estimated 
related costs to society attributed to exposure to EDs. 

The  findings  of  this  Fitness  Check  formed  an  important  contribution  to  the  Chemicals  Strategy  for 
Sustainability under the European Green Deal110. This strategy was part of the Commission’s Work 
Programme for 2020111. 

2  Organisation and timing 
The  pre-existing  Inter-service  Steering  Group  (ISG)  on  endocrine  disruptors  was  used  to  steer  the 
process  and  provide  input.  The  ISG  comprised  representatives  from  the  Directorate  Generals  for 
Agriculture  and  Rural  Development  (AGRI),  Environment  (ENV),  Internal  Market,  Industry, 
Entrepreneurship  and  SMEs  (GROW);  Health  and  Food  Safety  (SANTE),  Employment,  Social 
Affairs  and  Inclusion  (EMPL),  Maritime  Affairs  and  Fisheries  (MARE),  Research  and  Innovation 
(RTD),  Justice  and  Consumers  (JUST),  Trade  (TRADE),  Legal  Service  (SJ),  Joint  Research  Centre 
(JRC) and the Secretariat General (SG). 

A meeting with DGs directly responsible for the implementation of the Commission communication 
(DGs ENV, GROW, SANTE, EMPL, JRC and SG) was held to kick-off the Fitness Check. The ISG 
met  twice  during  the  evaluation  process  and  provided  feedback  through  two  written  consultations 
(Table 12.1). 

109COM(2018) 734  
110COM(2019) 640  
111https://ec.europa.eu/info/publications/2020-commission-work-programme-key-documents_en 

120 

 
 
 
                                                      
Table 12.1 Meetings of the Endocrine Disruptor Inter-service Steering Group and informal task 
force 

Date 
13 March 2019 
19 July 2019 

08 April 2020 

05 May 2020 

22 May 2020 

Nature of meeting 
Inter-DGs meeting to discuss operational plans 
Agreement of ISG on draft methodology, evaluation 
questions and stakeholder consultation strategy 
Written  consultation  of  ISG  on  the  draft  evaluation 
report (SWD) for submission to the RSB 
Meeting  of  ISG  to  discuss  comments  on  the  draft 
evaluation report (SWD) 
Written  consultation  on  the  revised  draft  evaluation 
report (SWD) for submission to the RSB  

3  Exceptions to the better regulation guidelines 
No exceptions were made to the Better Regulation Guidelines112 during this Fitness Check. 

4  Consultation of the Regulatory Scrutiny Board 
An upstream consultation of the Regulatory Scrutiny Board (RSB) of the European Commission on 
the planned methodology for the Fitness Check was held on 3 October 2019. A draft version of the 
evaluation report (Staff Working  Document) was submitted to the RSB on 26 May 2020. The RSB 
issued its positive opinion on 24 June 2020. The Board made a number of recommendations to further 
improve the report. These were addressed in the revised report as follows: 

the 

sensitive 

RSB recommendations 
(B) Summary of findings 
The  Board  appreciates  the  efforts  put  in 
analysing  the  wide  range  of  legislation 
issue  of 
dealing  with 
regulating  endocrine  disruptors.  The  Board 
notes the additional information provided in 
advance of the meeting. 
The  Board  gives  a  positive  opinion.  The 
Board also considers that the report should 
further 
the 
following aspects: 
(1)  While  acknowledging  that  the  subject 
matter of the fitness check is very technical, 
the  report  is  not  sufficiently  accessible  to 

improve  with 

respect 

to 

Modification of the report 

(1)  Efforts  were  made  to  remove  or  better  explain 
technical terms and to use fewer abbreviations or re-
state  them  in  full  at  the  beginning  of  each  section. 
The section on the State of Play of the 34 regulatory 
instruments  within  the  scope  of  the  Fitness  Check 
was  moved  to  an  annex  and  replaced  by  a  table 
shortly  stating  the  intervention  logic  and  most 
relevant  points  related  to  the  presence  or  absence  of 
ED-specific provisions. 

112https://ec.europa.eu/info/better-regulation-guidelines-and-toolbox_en 

121 

 
 
 
 
 
 
 
 
 
 
 
                                                      
RSB recommendations 
the non-expert reader. 

(2)  The  report  does  not  clearly  explain  the 
uncertainties  and  the  political  sensitivities 
relating to regulation in this area. 

(3)  The  conclusions  of  the  analysis  are  not 
sufficiently  clear  to  inform  future  policy 
intervention(s). 

(C) What to improve 
(1) To make the report more accessible, the 
introduction  should  succinctly  present  the 
landscape  of  endocrine  disruptors  in  the 
EU.  It  should  give  basic  information,  such 
as  the  number  of  tested,  identified  and 
banned  substances  per  type  of  legislation, 
the  length  of  the  testing  procedure,  costs, 
etc. It should better explain how the results 
of this fitness check could feed into policy-
making.  The  report  should  avoid  overlaps 
and  could  move  much  of  the  information 
provided on the ‘state of play’ to an annex. 
(2)  On  the  methodology,  the  report  should 
better  explain  how  the  case  studies  were 
selected and assess how representative they 
are. The report should present the views of 
stakeholders  in  a  more  nuanced  way.  It 
should  clearly  break  down 
responses 
according  to  stakeholder  groups  and  be 
more  explicit  about 
their  opinions  on 
particular issues raised in the consultations. 
To  the  extent  possible,  it  should  assess 
stakeholder  views  against  other  available 
evidence. 
(3)  The 
should  draw  clearer 
conclusions, both in the sub-sections and in 
the  concluding  chapter.  Firstly,  it  should 
better  distinguish  between  issues  where 
policy conclusions can be drawn with some 
degree  of  certainty  and  where  further 
assessment is necessary.  
Secondly,  the  conclusions  on  the  different 
evaluation  criteria  should  be  coherent  with 

report 

to 

introduction  was  extended 

Modification of the report 
(2)  The 
include 
reference to the specific uncertainties surrounding the 
related  political 
assessment  of  EDs  and 
sensitivities  with  respect  to  the  possibilities  to  set  a 
‘safe  threshold’  and  throughout  the  text  more  focus 
was  put  on 
risk 
the  consequent 
assessment/management options. 

impact  on 

the 

(3) The conclusions were reinforced to include more 
concrete takeaway messages from the findings of the 
Fitness  Check,  which  could  inform  future  policy 
interventions. 

(1) More background information on the landscape of 
EDs  in  the  EU  was  added  to  the  introduction 
including a table of EDs identified at EU level. Costs 
and  duration  of  testing  was  introduced  in  the 
effectiveness  section.  Sections  summaries  and  the 
conclusions were made more concrete with respect to 
policy 
findings 
interventions.  The  ‘state  of  play’  was  moved  to  the 
annex 

support 

future 

could 

that 

(2) An additional description of how the case studies 
were  selected  was  included  in  the  methodology.  A 
breakdown  of  responses  according  to  stakeholder 
groups  has  been  added  and  for  some  of  the  survey 
questions  an  assessment  of  the  differing  views  has 
been added. 

(3)  The  body  of  the  text  was  checked  and  some 
additional  points  were  added  to  the  summaries  of 
each  sub-section  addressing  the  evaluation  criteria. 
The  conclusion  section  has  been  rewritten,  checking 
for  coherence  with  the  summaries  in  each  sub-
section,  focusing  on  issues  that  could  inform  future 
policy interventions. The aspect of simplification was 
considered  further  and  some  of  the  conclusions  are 

122 

 
 
 
 
 
 
 
 
 
 
 
for 

without 

simplification 

fitness  check, 

RSB recommendations 
the presented analysis and should cover all 
identified issues.  
the 
Thirdly,  being  a 
conclusions  should  put  a  greater  focus  on 
the  potential 
and 
reduction of regulatory burdens.  
Finally,  the  report  should  more  clearly 
bring  out  the  main  takeaways  for  future 
policy-making, 
formulating 
concrete  solutions  as  this  should  rather  be 
dealt  with  in  a  potential  future  impact 
assessment. 
(4)  While  the  report  focuses  primarily  on 
the  science-based  assessment  of  endocrine 
disruptors,  it  is  apparent  from  the  analysis 
that there are also important policy choices 
involved.  It  should  better  explain  that  the 
choice  between  different  approaches  (e.g. 
applying  a  generic  vs.  specific 
risk 
approach 
endocrine 
disruptors)  concerns  uncertainty  about  the 
likelihood  of  damages  and 
the  value 
judgement on acceptable risks. 
The  report  should  elaborate  on  this  issue 
and any implications for the conclusions. 

regulating 

to 

Some more technical comments have been 
sent directly to the author DG. 

Modification of the report 
strengthened  with  respect 
this  point.  Some 
additional points were taken forward to the Executive 
Summary. 

to 

(4)  The  scientific  uncertainty  (“threshold  question”) 
underlying  the  choice  between  the  generic  risk  and 
the  specific  risk  management  approach  is  now 
explained  in  the  coherence  section,  as  well  as  the 
conclusions.  The  implications  of  this  distinction  are 
also  used  to  draw  a  conclusion  on  the  need  for 
consistent risk management principles. 
The  coherence  section  explains  the  different  risk 
management  approaches  in  the  context  of  the 
precautionary  principle,  as  well  as  the  need  to 
consider  trade-offs  and  to  apply  the  risk-benefit 
approach in certain sectors. 

Specific  comments 
addressed. 

to 

the  authors  were  also 

5  Evidence, sources and quality 
The sources of evidence and their quality are described in  Annex 3. These included the findings of 
previous fitness checks and evaluations, a series of case studies, and the results of public, stakeholder 
and  SME  consultations.  No  external  expertise  was  used,  apart  from  ad  hoc  consultations  with  EU 
agency  staff  related  to  EU  chemical  safety  assessments.  All  of  the  work  was  conducted  by 
Commission staff, with no external studies being performed. 

123 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Annex 2.  Synopsis report: stakeholder consultation activities 

1  Summary 
An important element of the Fitness Check is a consultation strategy aimed at citizens, stakeholders 
and companies. 

In the public consultation, 474 responses were received over a twelve-week period from 16/12/2019 
to 09/03/2020. The survey, which was translated into all official EU languages, was designed to gain 
the perspective of the citizen, rather than stakeholders or companies, who were targeted via separate 
surveys.  In  total,  431  of  the  474  responses  (91%)  came  from  citizens.  A  majority  of  citizens  felt 
informed  about  endocrine  disruptors  and  considered  that  their  effects  on  health  and  wildlife,  while 
poorly understood, do represent a concern. Similarly, a majority felt informed about the regulation of 
endocrine disruptors, but do not feel that the current regulatory framework is sufficiently protective. A 
majority of respondents also expressed the view that the EU should have the same approach or more 
consistent approach for both identifying and managing the risks of exposure to endocrine disruptors. 
Opinions were divided on whether animal testing is minimised in the assessment process. Similarly, 
there  were  mixed  views  on  whether  the  cost  of  regulatory  action  is  proportionate  to  the  benefits 
accrued for human health, wildlife and the economy. In general, the respondents considered that EU 
laws  on  endocrine  disruptors  are  relevant  to  societal  concerns,  and  that  regulatory  action  should  be 
taken at the EU level. 

In  the  stakeholder  consultation,  183  responses  were  received  over  an  eight-week  period  from 
06/12/19  to  31/01/20.  The  respondents  were  businesses,  public  authorities,  academics,  research 
organisations, and civil society organisations. A large majority (93%) of the respondents considered 
that  the  absence  of  harmonised  criteria  for  identifying  endocrine  disruptors  across  sectors  is 
problematic.  A  smaller  majority  (53%)  considered  that  this  harmonisation  should  be  achieved  by 
introducing an endocrine disruptor category under the classification and labelling legislation. Around 
three quarters said they were aware of inconsistencies, gaps or overlaps in the regulatory framework, 
and a similar proportion were aware of inadequacies in the availability of regulatory test methods. A 
large majority (88%) reported an increase in costs to comply with EU laws on endocrine disruptors. 

The results of the stakeholder consultation also give a detailed breakdown of stakeholder views on the 
effectiveness  of  legislation  in  specific  sectors  (REACH,  cosmetics,  biocides,  plant  protection 
products). This includes the perceived effectiveness in protecting people and wildlife, improving the 
functioning  of  the  Single  Market,  enhancing  competitiveness  and  innovation,  and  promoting 
alternatives to animal testing. Opinions were typically divided on these issues. However, in relation to 
exposure  to  chemical  mixtures,  there  was  a  tendency  to  consider  the  regulatory  framework  as 
insufficiently protective. 

The answers to additional questions confirmed that a majority of stakeholders consider the objectives 
of  the  regulatory  framework  to  be  relevant  in  addressing  health  and  environmental  concerns. 
Moreover,  the  prevailing  view  was  that  regulatory  actions  should  be  taken  at  the  EU  rather  than 
Member State level. 

An additional survey, targeting micro, small and medium-sized enterprises (SMEs), was conducted 
through  the  Enterprise  Europe  Network  and  was  open  from  01/02/2019  to  09/03/2020.  Responses 
were  received  from  70  SMEs.  In  general,  opinion  was  divided,  or  not  expressed,  across  a  range  of 
questions.  However,  many  respondents  considered  the  regulatory  process  to  identify  and  control 

124 

 
 
chemicals  with  endocrine  disrupting  properties  to  be  effective  in  protecting  people  and  wildlife,  in 
improving  the functioning of the internal  market, and  enhancing competitiveness  and innovation. A 
majority considered that the lack of a hazard category for the classification and labelling of endocrine 
disruptors poses a problem for their consistent identification and risk management. On the question of 
EU-added  value,  most  respondents  reported  that  unilateral  Member  State  actions  had  not  affected 
their company. 

2  Introduction and approach 
Stakeholder  consultation  was  a  key  component  of  this  Fitness  Check  to  collect  views  and  factual 
information  in  response  to  the  evaluation  questions  and  to  ensure  a  balanced  and  comprehensive 
assessment of the legislative framework.  

The objectives of the consultation activities were to: 

  Assess public concerns and needs with respect to endocrine disruptors in the EU. 
  Evaluate to what extent current EU legislation meets the concerns and needs of citizens. 
  Collect views on possible lack of legislative coherence of EU legislation with respect to EDs 

 

and possible impacts on stakeholders.  
Identify  any  inconsistencies  in  the  legal  framework  for  endocrine  disruptors  and  their 
consequences for small companies 

  Collect  information  on  the  effectiveness  of  the  current  EU  legislation  for  the  identification 

and risk management of endocrine disruptors.  

  Collect information on the efficiency of the current procedures for the identification and risk 

 

management of endocrine disruptors.  
Identify opportunities for improving the way endocrine disruptors are assessed, managed and 
potential risks communicated 

The consultation strategy developed for the purpose of this Fitness Check113 comprised: 

  presentation  of  the  methodological  approach  at  the  First  Annual  Forum  on  Endocrine 

 
 
 

Disruptors on 8 November 2019; 
an open public consultation from 16/12/2019 to 09/03/2020; 
a stakeholder consultation from 06/12/19 to 31/01/20; 
an SME panel through the Enterprise Europe Network from 01/02/2019 to 09/03/2020.  
The open public consultation and SME panel were conducted in all official EU languages, while the 
stakeholder  consultation  was  conducted  in  English.  Reports  on  the  results  of  open  public 
consultation114 and stakeholder consultation115 are available via the JRC Publications Repository. The 
public consultation report is also available via the Better Regulation (Have Your Say) website116. 

3  Stakeholder groups covered by the consultation activities 
In line with the consultation strategy, input from a wide range of stakeholders was collected: 

113https://ec.europa.eu/info/sites/info/files/food-farming-
fisheries/key_policies/documents/20191120_ed_consultation_strategy.pdf  
114https://publications.jrc.ec.europa.eu/repository/handle/JRC120369 
115https://publications.jrc.ec.europa.eu/repository/handle/JRC120148 
116https://ec.europa.eu/info/law/better-regulation/have-your-say/initiatives/2142-Fitness-Check-on-endocrine-
disruptors/public-consultation 

125 

 
 
 
                                                      
  Public  authorities,  notably  competent  authorities  and  relevant  EU  Agencies  responsible  for 

 

the implementation of relevant EU legislation 
Industry  associations  covering  both  the  chemicals  industry  and  downstream  sectors 
(manufacturers  and  importers  of  chemicals,  distributors  of  substances  and  mixtures, 
formulators, downstream users, manufacturers and importers of products/articles, retailers) 
  Companies in the chemicals industry and downstream sectors, including Small and Medium-
sized  Enterprises  (SMEs)  (manufacturers  and  importers  of  chemicals,  distributors  of 
substances  and  mixtures,  formulators,  downstream  users,  manufacturers  and  importers  of 
products/articles, retailers) 

  Consultants – professional consultancies, law firms, compliance testing companies 
  Civil society organisations – with the objective to protect human health and the environment 
from exposure to harmful substances via the workplace, consumer products or environmental 
media. 

  Civil society organisations – with animal welfare objectives aimed at reducing use of animals 

for scientific purposes (i.e. testing for ED properties) 

  Trade  unions  that  represent  workers  that  manufacture  or  use  chemicals  within  the  chemical 
industry,  downstream  sectors  or  use  chemicals,  as  substances,  mixtures  or  articles,  as 
industrial/professional users 

  Academics/research institutes/think tanks/scientific societies contributing to the development 
of methods and methodologies for the identification and assessment of endocrine disrupting 
substances. 

  Consumers / workers /citizens 
 

International partners and stakeholders of third countries  

Error! Reference source not found. demonstrates how each of the tools mentioned above was used to 
collect information from different categories of stakeholders. 

Table 13.1 Different stakeholder groups consulted 

Public consultation 

SME panel 

Stakeholder consultation 

Public authorities 
Industry associations 
Companies / SMEs 
NGOs 
Consumer 
associations 
Trade unions 
Academia  /  research 
institutes 
Consumers / workers 
/ citizens 

 

 

 
 
 
 
 

 
 

These  different  consultation  activities  and  tools  allowed  receiving  feedback  from  all  stakeholder 
groups. A summary of the  views  expressed in  each consultation is provided below. It is recognised 
that the results of any survey are associated with an inevitable bias towards those who have an interest 
in  responding.  Therefore,  observations  are  stated  in  terms  of  numbers  or  percentages  of  the 
respondents. 

126 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
4  Outcome of the public consultation  

  Respondents 

4.1
A  total  of  474  respondents  provided  an  answer,  of  which  90%  are  EU  citizens,  3%  are 
academic/research institutions and 2% non-governmental organisations. 

As regards the origin of the respondents participating to the survey, most answers were received from 
France (40%), Germany (17%), Spain (14%), Belgium (5%) and Finland (5%). 

Analysis of the survey results for attempts to bias the conclusions revealed no obvious re-occurring 
pattern across the answers. Ten percent of the responses were from non-citizens, but these show no 
alignment to a common position and do not influence significantly the results.   

  How well informed do citizens feel? 

4.2
A majority of the respondents consider themselves to be very well informed (14%) or reasonably well 
informed  (49%)  about  endocrine  disruptors,  as  opposed  to  feeling  poorly  informed  (31%)  or  not 
informed at all (6%). 

The  main  sources  of  information  on  endocrine  disruptors  used  by  the  respondents  are  specialised 
scientific  sources  (246),  general  news  coverage  (222),  social  media  (178),  education  and  training 
sources (131) and other sources (118).   

A  majority  of  the  respondents  feel  informed  about  the  decisions  made  in  the  EU  with  regard  to 
endocrine disruptors (11% very well informed; 57% somewhat informed). A minority (21%) do not 
feel informed, but trust regulators to keep them safe, while 11% replied that they do not know. 

Fifty-four percent of the respondents do not think that the effects on endocrine disruptors on public 
health  and  the  environment  are  understood  and  38%  think  the  effects  are  understood  to  a  certain 
extent as opposed to 5% that think effects are not understood. 

Twenty-five  percent  of  respondents  (118)  gave  details  on  the  source  of  information  they  mainly 
consult (open question Q2) (Figure 13.1). 

127 

 
 
 
 
Figure 13.1. Distribution of responses for Q2. Multiple answers were possible. Total number of responses 
(n=118). 

From the open box ‘other: please specify’ (Figure 13.2), data and reports from NGOs, environmental 
and  human  health  associations  (e.g.  Greenpeace,  PAN,  Free  Europe  etc.),  non-profit  networks  for 
consumers  and  specific  consumer  products  represent  the  main  source  of  information  across  all 
respondents. Specialised scientific sources include scientific and academic reviews (Pubmed search), 
books and publicly available databases. This type of information is also enriched by online search on 
the subject of endocrine disruptors, specialised and general websites (NGOs portals, documentaries, 
Wikipedia,  Google)  together  with  newspapers  consultation.  One  third  of  all  respondents,  mainly 
involved in education or health professions (academia, physicians) reported to attend trainings and to 
participate to conference or meetings. 

Figure 13.2. Distribution of responses for Q2. Other sources of information 

128 

 
 
 
 
 
 
  Public views on effectiveness 

4.3
The majority of respondents (54% to 74%) considered that EU laws did not protect them at all or only 
to a small extent  from exposure to  endocrine disruptors across  all of the potential exposure sources 
listed in the survey. The four exposure sources where respondents consider that EU laws protect them 
the least are personal care products, food contact materials, clothing and home/office. 

Sixty-one percent of the respondents consider that they are less protected by EU laws from endocrine 
disruptors  than  from  other  toxic  chemicals,  such  as  carcinogenic  or  mutagenic  substances,  or 
substances toxic to reproduction with 20% considering that they are protected to the same extent. 

In general, over 60% of respondents consider that EU laws offer a low level of protection for one or 
more life stages with the highest number of respondents concerned about adolescents (75%) and the 
lowest numbers concerned about pregnant women, foetuses and newborns (62% to 66%).  

In their free text replies, 70 respondents (open question Q5) considered not be protected at all or only 
to a small extent (56% and 11%) from combined exposures, mixtures and cocktail effects of potential 
endocrine  disruptors  and  their  presence  in  toys,  industrial  chemicals,  thermo-paper,  pesticides, 
biocides, perfumed products, medicinal products. Other concerns, to a lesser extent, were indoor air, 
car air filters, nanoparticles, construction materials, plastics and utensils. 

Ninety-three percent of respondents believe that endocrine disruptors contribute to a large or moderate 
extent to some human diseases or health conditions such as infertility, cancer or obesity. 

From 72% to 81% of respondents consider that EU laws offer a low level of protection for wildlife 
such  as  insects,  including  bees  and  other  pollinators  (81%),  fish  and  amphibians  (80%),  other 
invertebrates, such as snails, shrimps or worms (79%), birds and reptiles (76%), mammals (74%) and 
plants (72%). 

A majority of respondents expressed the view that the EU should have the same approach or the same 
approach  to  the  extent  possible  across  regulatory  sectors  for  both  identifying  endocrine  disruptors 
(86%) and managing the risks of exposure to endocrine disruptors (84%). 

Many  of  the  respondents  are  of  the  opinion  that  endocrine  disruptors  are  insufficiently  identified 
across a range of sectors, particularly in furnishing and electrical and electronic equipment (see figure 
below). 

The  majority  of  respondents  are  also  of  the  opinion  that  EU  laws  insufficiently  manage  the  risks 
linked to endocrine disruptors across all sectors. For example, the number of respondents considering 
that endocrine disruptors are not well managed in the pesticide sector is 73% compared with 15% who 
think endocrine disruptors are well managed or fairly well managed and 12% who do not know or did 
not  reply.  For  medical  devices,  53%  of  respondents  consider  that  endocrine  disruptors  are  not  well 
managed compared with 22% who think that they are well managed or fairly well managed and 25% 
who do not know or did not reply. 

  Public views on efficiency 

4.4
Forty-four percent  of the respondents  consider that the costs (e.g. time, resources, use of laboratory 
animals) of EU laws on endocrine disruptors are proportionate for the benefits accrued compared with 
26% who consider costs are only to a small extent or not at all proportionate. Thirty percent replied 
that they do not know. 

129 

 
 
In general, the respondents consider that EU laws on endocrine disruptors generate slightly more costs 
for the agricultural and industrial sectors compared with costs to citizens or ethical costs.  

In their free text replies, 40 respondents gave further insights regarding the costs to which extent EU 
laws  generate  on  endocrine  disruptors  (open  question  Q15).  The  majority  (75%)  highlighted  high 
costs in terms of healthcare, diseases and environmental health and finally for citizens which the EU 
is  generating  by  means  of  inaction.  Other  costs  are  generated  by  unnecessary  use  of  animals  and 
lobbying.  Many  respondents  (20%)  while  declaring  not  to  be  aware  of  costs,  suggested  water 
treatment and soil. 

EU laws on endocrine disruptors are believed to generate benefits for the EU market by about half of 
the respondents (49% agree fully or to a moderate extent, while 24% agree to a small extent or don’t 
agree at all and 27% don’t know or did not reply). Opinion is also divided on the extent to which EU 
laws on endocrine disruptors are seen to benefit human health and wildlife. 

  Summary of public views on regulatory testing and animal welfare 

4.5
Thirty-seven percent of the respondents think that animal testing for endocrine disrupting properties in 
the EU is insufficiently minimised, whereas 28% consider animal testing to be either minimised to the 
extent possible (23%) or fully minimised (5%). Thirty-five percent replied that they do not know. 

  Public views on EU-added value 

4.6
In  terms  of  which  bodies  should  regulate  to  protect  people  and  wildlife  from  harm  caused  by 
endocrine disruptors, most respondents expressed the view that this should be done by EU authorities 
(432),  and  many  respondents  considered  that  national  authorities  (356),  international  organisations 
(292)  and  local/regional  authorities  (238)  should  act.  For  this  question,  the  numbers  of  respondents 
are given, rather the percentage values, since it was possible to select more than one option. 

  Public views on relevance 

4.7
In terms of areas where the EU needs to significantly step up its efforts, the respondents prioritised as 
follows:  reducing  exposure  of  humans  (88%),  reducing  exposure  to  wildlife  (84%),  identifying 
endocrine  disruptors  (80%),  and  adopting  a  coherent  approach  to  identification  and  management  of 
endocrine disruptors (79%). Fewer respondents consider that a lot of efforts are needed by the EU to 
reduce the burdens and costs to business (30%). 

  Additional comments made by citizens 

4.8
There  were  196  responses  to  the  final  question  (Q19)  which  asked  respondents  to  provide  any 
additional  comment  or  suggestion  that  they  considered  relevant  for  the  endocrine  disruptors  Fitness 
Check. 

Ten of the respondents were on behalf of NGOs (advocacy for environment, justice, animal welfare), 
two  were  representing  cancer  prevention  associations,  and  one  spoke  on  behalf  of  electronic 
equipment  industry  association.  The  responses  from  stakeholders  (NGOs,  industry  association  and 
cancer  associations)  were  removed  from  the  summary  of  citizens’  responses,  thus  leaving  183 
responses.  This  did  not  affect  either  the  contribution  to  the  public  consultation,  by  means  of 
percentages, or main key messages. 

In  addition,  five  respondents  were  researchers  from  (academia,  research  institutes),  six  were  health 
professionals,  such  as  doctors  (general  medicine,  endocrinology,  paediatrics)  and  one  was  from  a 
private  law  firm.  These  responses  were  included  in  the  following  analysis,  on  the  basis  that  these 
respondents were experts replying as citizens,  

130 

 
 
Twenty eight percent of these respondents (52 out of 183) expressed their concerns about the presence 
of  endocrine  disruptors  in  the  environment  and  many  products  they  might  be  in  contact  with. 
Respondents in this group asked for more attention and immediate actions to prevent potential toxic 
effects  of  EDs  on  humans  and  the  environment.  Many  advocated  for  an  immediate  ban  of  such 
substances,  stricter  measures  for  their  identification  on  the  basis  of  precautionary  principle,  more 
stringent  control  and  regulation  by  authorities.  Many  fear  the  presence  of  endocrine  disruptors  in 
consumer  goods  (such  as  personal  care  products,  toys,  food  contact  materials,  and  children’s 
products) where they consider EDs should be forbidden. Despite acknowledging the difficulties in the 
identification  of  chemicals  as  potential  EDs,  respondents  asked  for  limited  use  of  any  chemical 
showing concern either for human health or environment. In addition, industry was asked to develop 
safer alternatives.  

Fifteen percent of respondents (28 out of 183), expressed concerns about the role of companies and 
their  potential  lobbying  of  EU  institutions.  This  group  feared  that  economic  interests  are  politically 
favoured  over  human  and  environment  health.  Independent  assessment  of  substances  was  also 
requested together with independent research through public funds. In this regard, 12% of respondents 
(22  out  of  183)  asked  for  more  information  on  industry  activities,  on  production  and  safety 
assessments  of  substances.  They  asked  for  better  information  about  marketed  products;  more 
transparency  on  product  labelling;  greater  awareness  of  the  EU  policies,  better  information  and 
training offerings for health professionals; more instructions and advice to consumers; multiplication 
of the information channels on research, diagnostics and regulatory decisions on endocrine disruptors.  

Approximately  10%  of  respondents  highlighted  the  need  for  stronger  action  in  response  to  the 
increased evidence of ED-related diseases (e.g. obesity, cancer, infertility etc.). They asked for more 
studies  on  biomonitoring  and  exposure  to  endocrine  disrupting  chemicals,  including  requests  to 
further  the  knowledge  on  mixtures,  combined  exposures  and  cocktail  effects.  This  group  advocated 
for  attention  to  vulnerable  groups,  especially  children,  including  more  stringent  measures  on  the 
exposure  to  EDs,  considering  the  evidence  of  neurobehavioral  disorders  and  IQ  impairment.  Two 
respondents  claimed  that  they  suffered  adverse  health  effects  resulting  from  exposure  to  endocrine 
disruptors. 

Citizens (3.8% of respondents) commented on the need to identify endocrine disruptors in consumer 
products,  especially  detergents,  sanitizers  and  medicines,  alongside  the  promotion  of  research 
activities to develop better bioanalytical methods (1.6%) and application of novel methodologies for 
ED identification and safety testing of substances which would ultimately reduce the use of animals 
(2%).  

According  to  approximately  3%  of  respondents,  clear  identification  criteria  and  eventually  hazard 
categories for endocrine disruptors are still needed, including harmonisation across different product 
sectors,  to  reach  the  highest  level  of  protection  for  humans  and  the  environment.  Another  0.5%  of 
respondents  considered  that  new  hazard  categories  for  classification  and  labelling  is  scientifically 
questionable,  may  lead  to  unnecessary  administrative  burden  in  regulatory  decision  making,  and  it 
would have questionable value in terms of risk communication and management.  

Citizens  (2.7%)  also  considered  it  essential  that  endocrine  disruptors  are  regulated  and  monitored 
consistently across the EU, and that measures are implemented in each Member State. The EU should 
monitor and impose heavy sanctions on the Member States that do not comply with the rules or make 
it  difficult  to  comply  with  them.  Where  unilateral  actions  are  taken  by  single  Member  States  those 

131 

 
 
actions  should  be  quickly  adopted  at  EU  level.  This  group  expressed  concerns  about  the  safety  of 
products imported from non-EU countries that do not have similar standards. 

According to 4.4% of respondents further studies are also needed on the quality  of soils, water, tap 
water, in particular surface water installations but also aquatic ecosystems.  

Seventeen percent of respondents (29 out of 183) expressed their scepticism about the ability of the 
EU to act and the poor measures taken so far. They lamented delays and inadequacies of current EU 
regulations, which do not protect people and the environment against exposure to EDs. In particular, 
the following were mentioned: delays in the implementation of the REACH regulation and failure to 
implement  a  number  of  recommendations  from  the  EU  Parliament  and  Council;  delays  in  the 
substitution  of  harmful  chemicals  or  their  complete  ban;  and  delays  of  the  application  of  measures 
despite evidence being available for the past twenty years. In general, this group thought that little or 
nothing  has  been  done  and  too  many  chemicals  were  left  on  the  market  without  proper  testing  and 
controls.  Moreover,  the  identification  of  EDs  was  considered  insufficient.  Negative  comments  from 
44% of this group were also about the questionnaire itself which was considered unclear (Q11, Q14, 
Q16) and unsuitable for the general public. It was also noted that questions 15 and 16 could only be 
answered  hypothetically  as  none  of  pesticides  or  biocides  have  been  identified  based  on  new  test 
procedures (implemented in 2018). 

5  Outcome of the stakeholder consultation  

  Structure of survey 

5.1
The  survey  was  structured  into  different  parts.  The  first  section  concerned  information  about  the 
respondents such as category of stakeholder, country of origin and residency, and regulatory sector of 
interest. The second section asked about the level of familiarity with the different pieces of legislation 
within  the  scope  of  the  Fitness  Check  and  then  went  on  to  ask  questions,  seeking  views  and 
information  on  different  aspects  of  coherence,  effectiveness,  efficiency,  relevance  and  EU-added 
value of the current approaches to identification, assessment and management of endocrine disruptors 
in the EU legislation. 

Apart from the introductory section  related to respondent  characteristics, the survey did  not include 
any  mandatory  fields.  It  was  therefore  possible  for  respondents  to  leave  one  or  more  of  the  36 
questions unanswered. As a result, the total number of responses to each question varied.  

Some  questions  were  aimed  at  specific  categories  of  stakeholders:  questions  25,  26  and  29  were 
intended for business associations, company/business organisations and public authorities; questions 
27,  28  and  35  were  intended  for  business  associations  and  company/business  organisations.  These 
questions did not appear to respondents identifying themselves in other categories. 

  Respondents 

5.2
Overall, 183 replies were received in the stakeholder consultation. A quality check of the responses 
revealed the presence of 11 replicates in the answers. Analysis the origin of these replicates showed 
that some respondents replied more than once by mistake (twice, and in once case trice) and covered 
evenly all categories of stakeholders. Removal of these replicates leads to a variation of no more than 
one percent for each question. 

132 

 
 
 
Analysis  of  the  survey  results  for  attempts  to  bias  the  conclusions  indicated  five  clusters  of  similar 
patterns  of  answers  for  both  closed  or  open  types  of  questions.  Nevertheless,  the  fact  that  these 
clusters represent fewer than six respondents shows that they are probably coordinated groups sharing 
similar  positions.  Furthermore,  they  cover  evenly  all  categories  of  stakeholders.  Removal  of  these 
similar types of responses (keeping only one per identified cluster) leads to a variation less than five 
percent in all cases. 

Taking into account these  two  points, the survey responses were  analysed without removing  any of 
the 183 answers.      

Replies  provided  to  the  survey  cover  all  categories  of  respondents  with  respect  to  their  stakeholder 
category (Table 13.2). 

Table 13.2 Respondents from different stakeholder groups consulted 

Stakeholder group 

No of responses 

Business associations 
Public authorities 
Company or business organisations   
Civil society organisations 
Academic/Research institutions 
Trade unions 

47 
35 
31 
27 
14 
11 

The  most  represented  country  is  Belgium  with  48  respondents,  followed  by  France  (27),  Germany 
(18) and Spain (11). 

Respondents  outside  of  the  EU  come  from  Switzerland  (6),  USA  (3),  Norway  (2),  Japan  (1)  and 
Turkey (1). 

The geographical scope of the respondents is 61% international and 39% national, regional or local. 

133 

 
 
 
 
 
 
 
 
Country 
Belgium 
France 
Germany 
Spain 
Denmark 
Italy 
United Kingdom 
Sweden 
Austria 
Bulgaria 
Luxembourg 
Finland 
Hungary 
Ireland 
Portugal 
Latvia 
Netherlands 
Poland 
Romania 
Slovenia 
Croatia 
Cyprus 
Lithuania 
Malta 
Slovak Republic 
Other (Please specify) 

Answers 
48 
27 
18 
11 
8 
7 
6 
5 
4 
4 
4 
3 
3 
3 
3 
2 
2 
2 
2 
2 
1 
1 
1 
1 
1 
13 

Percentage 
26% 
15% 
10% 
6% 
4% 
4% 
3% 
3% 
2% 
2% 
2% 
2% 
2% 
2% 
2% 
1% 
1% 
1% 
1% 
1% 
1% 
1% 
1% 
1% 
1% 
7% 

Among  economic  operators  (companies  and  business  associations)  and  public  authorities,  the  main 
sectors of interest are General Chemicals (14%), Biocidal Products (12%) and Cosmetics (11%). 

Sector 
General chemicals 
Biocidal products 
Cosmetics 
Plant Protection Products 
Food contact materials 
Detergents 
Food additives 
Medical devices 
Human and veterinary medicines 
Fertilisers 

134 

Answers 
51 
43 
40 
33 
30 
28 
25 
24 
20 
16 

Percentage 
14% 
12% 
11% 
9% 
8% 
8% 
7% 
6% 
5% 
4% 

 
 
 
 
 
Sector 
Water industry 
Waste/recycling industry 
Electric and electronic equipment 
Toys 

Answers 
16 
16 
15 
14 

Percentage 
4% 
4% 
4% 
4% 

  Familiarity of stakeholders with relevant legislation 

5.3
Q1. How familiar are you with the following pieces of legislation? 

The  familiarity  of  the  respondents  with  the  pieces  of  EU  legislation  included  in  the  scope  of  the 
Fitness Check may be relevant to the interpretation of the replies. 

Among the listed legislative instruments, the respondents are most familiar with the following pieces 
of legislation: 

Legislation 

Very 
familiar 

Fairly 
familiar 

A little 
familiar 

Not at all 
familiar 

REACH Regulation (EC) 1907/2006 

CLP:  Classification,  Labelling  and  Packaging  of 
substances and mixtures (EC) 1272/2008 

Biocidal Products Regulation (EU) 2012/528 

Cosmetic Products Regulation (EC) 1223/2009 

Plant Protection Products Regulation (EC) 1107/2009 

122 

113 

60 

59 

51 

32 

35 

57 

35 

41 

20 

17 

42 

35 

42 

2 

10 

13 

40 

38 

The respondents are least familiar with the following legislative instruments: 

Legislation 

Very 
familiar 

Fairly 
familiar 

A little 
familiar 

Not at all 
familiar 

Fertilisers  Regulation  (EC)  2003/2003  and  Regulation 
(EU) 2019/1009 

Medicinal Products for Humans Directive 2001/83/EC 

Marine Strategy Framework Directive 2008/56/EC 

Urban Waste Water Directive 91/271/EEC 

Veterinary Medicinal Products Regulation (EU) 2019/6 

In  vitro  Diagnostic  Medical  Devices  Regulation  (EU) 
2017/746 

21 

15 

15 

21 

16 

14 

18 

23 

16 

9 

14 

12 

36 

52 

48 

44 

40 

45 

91 

77 

85 

90 

97 

94 

  Stakeholder views on coherence (overall statistics) 

5.4
Q2. To what extent does the absence of harmonised criteria pose a problem to a coherent approach 
for the identification of endocrine disruptors? 

135 

 
 
 
 
 
 
Overall,  150  (93%)  of  the  respondents  consider  that  the  absence  of  harmonised  criteria  poses  a 
problem  to  the  identification  of  endocrine  disruptors  across  sectors,  while  11  (7%)  think  it  is  not  a 
problem, the criteria should be sector specific. 

Q3. Do you think that the lack of a hazard category covering endocrine disrupting properties in the 
CLP Regulation and/or GHS poses a problem for the coherent identification of endocrine disruptors? 

Opinion is divided on this topic with 94 of the respondents (53%) thinking that this is a problem for 
coherent ED identification, and 83 (47%) thinking it is not. 

Q4. Do you think that the lack of a hazard category covering endocrine disrupting properties in the 
CLP  Regulation  and/or  GHS  poses  a  problem  for  the  coherent  risk  management  of  endocrine 
disruptors? 

Opinion is divided on this topic with 86 of the respondents (51%) thinking that the lack of a hazard 
category is a problem for coherent risk management, and 84 (49%) thinking it is not a problem. 

Q5. Do you think that a category of suspected endocrine disruptor should be introduced? 

Some stakeholders have suggested to classify endocrine disruptors in one of three categories based on 
the level of evidence: i.e. known, presumed or suspected. 

With regard to the need of a category of suspected endocrine disruptors, opinion is again divided with 
89 respondents (53%) being in favour of introducing  a category for suspected endocrine disruptors, 
while 79 (47%) are not in favour.  

Q6.  Are  you  aware  of  any  inconsistencies  in  the  way  chemicals  are  identified  and  controlled  with 
regard to endocrine disrupting properties across regulated areas in the EU? 

Overall,  123  respondents  (73%)  are  aware  of  inconsistencies  in  the  way  endocrine  disruptors  are 
identified and controlled in the European Union, while 45 (27%) are not. 

Q7a.  In  your  opinion,  how  do  hazard-based  criteria  for  identifying  endocrine  disruptors  in 
combination with a hazard-based approach117 to decision-making affect the following objectives? 

A  majority  of  respondents  consider  that  the  use  of  hazard-based  criteria  for  identifying  endocrine 
disruptors  in  combination  with  a  hazard-based  approach  to  decision  making  would  affect  (very) 

117The terminology “hazard-based” and “risk-based” approaches is used in the context of consultation activities 
of this Fitness Check. The terms are equivalent to “generic risk” and “specific risk” approaches used elsewhere 
in the document. 

136 

 
 
 
 
 
 
  
                                                      
positively118 human health protection (93), and environmental protection (92) compared with 58 and 
54 who viewed these impacts (very) negatively119. 

The effects on "competitiveness and innovation" and on the "functioning of the internal market" are 
viewed more negatively than positively, although higher numbers of respondents indicate “no effect” 
or “don’t know”. 

Very 
positively 

Positively  No effect  Negatively 

Very 
negatively 

Don't 
know 

Human health protection 

Environmental protection 

Competitiveness 
innovation 

and 

Functioning of the internal 
market 

60 

62 

33 

34 

33 

30 

16 

9 

5 

9 

10 

19 

24 

26 

21 

29 

34 

28 

46 

23 

15 

15 

45 

56 

Q7b.  In  your  opinion,  how  do  hazard-based  criteria  for  identifying  endocrine  disruptors  in 
combination with a risk-based approach to decision-making affect the following objectives? 

Of  those  respondents  expressing  an  opinion  the  majority  view  positively  or  very  positively  a  risk-
based approach to decision making in relation to human health and environmental protection. 

The effects on "competitiveness and innovation" and on the "functioning of the internal market" are 
also  viewed  more  positively  than  negatively,  although  higher  numbers  of  respondents  indicate  “no 
effect” or “don’t know”. 

Very 
positively 

Human health protection 

Environmental protection 

Competitiveness 
innovation 

and 

Functioning  of  the  internal 
market 

60 

60 

37 

32 

Positively  No 

Negatively 

effect 

3 

4 

15 

18 

51 

49 

42 

28 

32 

33 

29 

28 

Very 
negatively 

Don't 
know 

10 

10 

4 

5 

14 

13 

43 

56 

Q8. Are you aware of any gaps or overlaps in the way endocrine disruptors are regulated in the EU? 

Overall,  127  respondents  (73%)  consider  that  there  are  gaps  or  overlaps  in  the  EU  legislation  on 
endocrine disruptors, while 46 (27%) do not. 

118Sum of respondents agreeing very positively or positively 
119Sum of respondents agreeing very negatively or negatively 

137 

 
 
  
 
 
 
 
                                                      
Q9. Have you experienced issues or problems because endocrine disruptors are regulated differently 
in the EU compared with non-EU countries? 

Opinion is divided with 81 respondents (51%) not experiencing issues or problems due to endocrine 
disruptors  being  regulated  differently  in  the  EU  compared  to  non-EU  countries,  while  81  (49%) 
reported problems. 

Q10. Do you have further comments on the coherence of the EU legislation with regard to endocrine 
disruptors? 

Ninety-four  respondents  provided  answers  to  this  open  question.  The  results  are  summarised  in  the 
respective sections of the Staff Working Document. 

5.5

  Stakeholder views on effectiveness (overall statistics) 

Q11a.  In  the  case  of  Biocidal  Products,  do  you  agree  that  the  regulatory  process  to  identify  and 
control  substances  with  endocrine  disrupting  properties  is  effective  in:  protecting  consumers, 
workers,  citizens  and  wildlife;  improving  the  functioning  of  the  internal  market ;  enhancing 
competitiveness and innovation; and promoting alternatives to animal testing. 

With regard to biocidal products, of those expressing an opinion there is a roughly even split between 
those  that  consider  the  regulation  is  effective  in  protecting  human  health  and  those  that  do  not: 
consumers (51 agree , 42 disagree, and 18 neither agree nor disagree), workers (46 agree, 43 disagree, 
and  19  neither  agree  nor  disagree)  and  citizens  exposed  via  the environment  (43  agree,  47  disagree 
and 21 neither agree nor disagree).  

When  it  comes  to  protecting  wildlife  the  number  of  respondents  agreeing  that  the  regulation  is 
effective decreases (35 agree, 50 disagree and 22 neither agree nor disagree). 

Of those expressing  an opinion, more respondents disagree than agree that the  provisions related to 
EDs  have  a  positive  effect  on  the  functioning  of  the  internal  market  (19  agree,  28  disagree  and  34 
neither agree nor disagree), on enhancing competitiveness and innovation (22 agree, 42 disagree and 
27 neither agree nor disagree) and on promoting alternatives to animal testing (24 agree, 40 disagree 
and 33 neither agree nor disagree). However, to these questions there are many respondents choosing 
“neither agree nor disagree” or “don’t know”. 

Q11b. In the case of Plant Protection Products, do you agree that the regulatory process to identify 
and  control  substances  with  endocrine  disrupting  properties  is  effective  in:  protecting  consumers, 
workers,  citizens  and  wildlife;  improving  the  functioning  of  the  internal  market ;  enhancing 
competitiveness and innovation; and promoting alternatives to animal testing. 

With regard to plant protection products, of those expressing an opinion there is a roughly even split 
between those that consider the regulation  is effective in protecting human  health  and those that do 
not:  consumers  (41  agree,  37  disagree,  and  24  neither  agree  nor  disagree),  workers  (37  agree,  36 
disagree, and 19 neither agree nor disagree) and citizens exposed via the environment (36 agree, 40 
disagree and 26 neither agree nor disagree).  

138 

 
 
 
 
 
When  it  comes  to  protecting  wildlife  the  number  of  respondents  agreeing  that  the  regulation  is 
effective decreases (34 agree, 43 disagree and 23 neither agree nor disagree). 

Of those expressing  an opinion,  more respondents disagree than agree that the  provisions related to 
EDs  have  a  positive  effect  on  the  functioning  of  the  internal  market  (21  agree,  31  disagree  and  22 
neither agree nor disagree), on enhancing competitiveness and innovation (23 agree, 38 disagree and 
18 neither agree nor disagree) and on promoting alternatives to animal testing (22 agree, 39 disagree 
and 24 neither agree nor disagree). However, to these questions there are many respondents choosing 
“neither agree nor disagree” or “don’t know”. 

Q11c.  In  the  case  of  REACH,  do  you  agree  that  the  regulatory  process  to  identify  and  control 
substances  with  endocrine  disrupting  properties  is  effective  in:  protecting  consumers,  workers, 
citizens  and  wildlife;  improving  the  functioning  of  the  internal  market ;  enhancing  competitiveness 
and innovation; and promoting alternatives to animal testing. 

With regard to the effectiveness of REACH in protecting human health and the environment there are 
fewer respondents selecting ‘neither agree nor disagree’ or choosing to select ‘don’t know’, than is the 
case for biocides or PPPs.  

Of those expressing an opinion there is a roughly even split between those that consider the regulation 
is effective in protecting human health and those that do not (consumers (57  agree, 62 disagree, and 
17 neither agree nor disagree), workers (56 agree, 59 disagree, and 18 neither agree nor disagree). A 
smaller  proportion  of  respondents  consider  that  the  regulation  is  effective  in  protecting  citizens 
exposed via the environment (46 agree, 63 disagree, and 26 neither agree nor disagree) or wildlife (43 
agree, 67 disagree, and 23 neither agree nor disagree). 

More  respondents  disagree  than  agree  that  the  regulation  (with  respect  to  EDs)  improves  the 
functioning  of  the  internal  market  (31  agree,  48  disagree,  and  36  neither  agree  nor  disagree)  or 
enhances competitiveness and innovation (24 agree, 50 disagree, and 34 neither agree nor disagree) or 
promotes  alternatives  to  animal  testing  (32  agree,  44  disagree,  and  38  neither  agree  nor  disagree). 
Again,  there  are  many  respondents  choosing  “neither  agree  nor  disagree”  or  “don’t  know”  to  this 
group of questions. 

Q11d.  In  the  case  of  Cosmetics,  do  you  agree  that  the  regulatory  process  to  identify  and  control 
substances  with  endocrine  disrupting  properties  is  effective  in:  protecting  consumers,  workers, 
citizens  and  wildlife;  improving  the  functioning  of  the  internal  market ;  enhancing  competitiveness 
and innovation; and promoting alternatives to animal testing. 

For  cosmetics,  more  respondents  disagree  than  agree  that  the  regulation  with  respect  to  EDs  is 
protecting consumer health (31 agree, 48 disagree, and 24 neither agree nor disagree) or worker health 
(24 agree, 49 disagree, and 28 neither agree nor disagree).  

Few  respondents  agree  that  it  is  improving  the  functioning  of  the  internal  market  (13  agree,  31 
disagree, and 44 neither agree nor disagree) or enhancing competitiveness and innovation (17 agree, 
30 disagree, and 37 neither agree nor disagree). However, the agree to disagree ratio changes around 
with  respect  to  promoting  alternatives  to  animal  testing,  where  34  moderately  or  strongly  agree 
compared  with  12  that  strongly  or  moderately  disagree.  The  number  that  “don’t  know”  or  “neither 
agree nor disagree” is rather high. 

139 

 
 
 
 
Q11e. In the case of Medical Devices, do you agree that the regulatory process to identify and control 
substances  with  endocrine  disrupting  properties  is  effective  in:  protecting  consumers,  workers, 
citizens  and  wildlife;  improving  the  functioning  of  the  internal  market ;  enhancing  competitiveness 
and innovation; and promoting alternatives to animal testing. 

For medical devices, a large proportion of respondents say they do not know about the effectiveness 
of the regulatory process (ranging from 59 to 72). Of those expressing an opinion, more respondents 
disagree  than  agree  that  it  is  protecting  consumers  (25  agree,  35  disagree,  and  15  neither  agree  nor 
disagree), protecting workers (23 agree, 29 disagree, and 19 neither agree nor disagree) or enhancing 
competitiveness and innovation (13 agree, 29 disagree, and 23 neither agree nor disagree). 

More respondents neither agree nor disagree that it is improving the functioning of the internal market 
(9 agree, 21 disagree, and 31 neither agree nor disagree) or promoting alternatives to animal testing 
(11 agree, 11 disagree, and 39 neither agree nor disagree) compared with those that agree or disagree. 

Q11f.  In  the  case  of  the  Water  Framework  Directive,  do  you  agree  that  the  regulatory  process  to 
identify  and  control  substances  with  endocrine  disrupting  properties  is  effective  in:  protecting 
consumers,  workers,  citizens  and  wildlife;  improving  the  functioning  of  the  internal  market ; 
enhancing competitiveness and innovation; and promoting alternatives to animal testing. 

Regarding the Water Framework Directive, more respondents disagree than agree that the directive is 
effective  in  minimising  the  exposure  of  citizens  (22  agree,  47  disagree,  and  12  neither  agree  nor 
disagree) or wildlife (27 agree, 47 disagree, and 12 neither agree nor disagree) to endocrine disruptors 
via the environment. However, the numbers of “don’t knows” are relatively high. 

Q12. Aggregate exposure to one substance from all exposure sources 

More  respondents  disagree  than  agree  that  the  current  regulatory  framework  protects  humans  (60 
agree, 96 disagree, and 6 neither agree nor disagree) or wildlife (39 agree, 91 disagree, and 14 neither 
agree  nor  disagree)  from  the  risks  associated  with  the  aggregate  exposure  to  one  substance  with 
endocrine disrupting properties from all exposure sources. 

Strongly 
agree 

Moderately 
agree 

Neither 
agree nor 
disagree 

Moderately 
disagree 

Strongly 
disagree 

Don't know 

25 

35 

6 

33 

63 

8 

19 

20 

14 

23 

69 

24 

Humans  are  protected 
by 
current 
regulatory framework  

the 

Wildlife  is  protected 
by 
current 
regulatory framework 

the 

140 

 
 
 
 
 
 
 
 
Q13. Combined exposure to multiple substances from all sources  

Compared  with  Q12,  a  larger  proportion  of  respondents  disagree  that  the  current  regulatory 
framework protects humans (46 agree, 100 disagree, and 14 neither agree nor disagree) or wildlife (27 
agree,  95  disagree,  and  23  neither  agree  nor  disagree)  from  the  risks  associated  with  the  combined 
exposure to different substances with endocrine disrupting properties (combined effects). 

Strongly 
agree 

Moderately 
agree 

Neither 
agree nor 
disagree 

Moderately 
disagree 

Strongly 
disagree 

Don't know 

14 

32 

14 

24 

76 

9 

9 

18 

23 

15 

80 

21 

Humans  are  protected 
by 
current 
regulatory framework 

the 

Wildlife  is  protected 
by 
current 
regulatory framework 

the 

Q14.  Do  you  think  that  the  following  groups  are  sufficiently  protected  from  exposure  to  substances 
with endocrine disrupting properties? 

For all population categories, the level of protection is regarded as insufficient by about two thirds of 
respondents  (ranging  between  56%  for  adults  in  general  to  66%  for  the  unborn  exposed  during 
pregnancy). 

Population category 

Unborn 
pregnancy 

through 

exposure 

during 

Newborn up to the age of 3 

Children until puberty 

Young persons around the age of puberty 

Pregnant women 

Adults in general 

People at work 

Elderly 

People with illnesses 

No 

90 

90 

90 

91 

87 

80 

85 

78 

81 

Yes 

47 

49 

49 

48 

52 

63 

54 

56 

46 

141 

Don't know 

34 

30 

30 

30 

29 

26 

30 

34 

43 

 
 
 
 
 
 
 
Q15. Are available regulatory tests sufficient to identify endocrine disruptors for humans  (including 
vulnerable groups) as well as wildlife? 

Overall,  116  respondents  (74%)  consider  the  available  regulatory  tests  insufficient  to  identify  EDs, 
while 41 (26%) consider the tests sufficient. 

Q16.  Are  current  provisions  for  data  requirements  laid  down  in  relevant  legislation  (REACH, 
Biocidal Products Regulation, Plant Protection Products Regulation) sufficient to identify endocrine 
disruptors for humans (including vulnerable groups) as well as wildlife? 

Similarly, 114 respondents (71%) consider that the data requirements laid down in relevant legislation 
(REACH, Biocidal Products Regulation, Plant Protection Products Regulation) are insufficient, while 
46 (29%) consider the requirements sufficient. 

Q17. Considering the information requirements of REACH, the Biocidal Products Regulation and the 
Plant  Protection  Products  Regulation,  do  you  think  the  likelihood  of  identifying  a  substance  as  an 
endocrine disruptor is lower under one of these regulations compared to the others? 

The  likelihood  to  identify  an  endocrine  disruptor  under  REACH,  the  Biocidal  Products  Regulation 
and the Plant Protection Products Regulation is about the same, according to 74 respondents (53%), 
and not the same according to 65 respondents (47%). 

Q18. Do you have any further comments on available regulatory test methods and data requirements 
under  REACH,  the  Biocidal  Products  Regulation,  the  Plant  Protection  Products  Regulation,  and 
other sector specific legislation? 

Sixty-three  respondents  answered  to  this  open  question.  The  results  are  included  in  the  relevant 
section of the Staff Working Document. 

Q19.  Do  you  agree  with  the  following  statement?  In  vitro  and/or  in  silico  methods  are  not  used 
systematically enough to prioritise further investigations. 

Among those who expressed an opinion, a majority of respondents think that in vitro and/or in silico 
methods are not used systematically enough to prioritise further investigations (80 agree, 7 disagree, 
and 38 neither agree nor disagree). 

Answers 

39 

41 

38 

5 

2 

41 

Strongly agree 

Moderately agree 

Neither agree nor disagree 

Moderately disagree 

Strongly disagree 

Don't know 

142 

 
 
 
  
 
Q20.  In  your  opinion,  is  the  impact  of  assessing  chemicals  for  endocrine  disrupting  properties  on 
animal welfare minimised in the EU? 

A bit more than half of the respondents expressing an opinion (54%) think that the impact of assessing 
chemicals for endocrine disrupting properties on animal welfare is minimised in the EU to the extent 
possible. 

Not at all 

Insufficiently minimised 

Minimised to the extent possible 

Don't know 

Answers 

12 

43 

64 

51 

Q21. Do you have recommendations on how to further minimise the impact of assessing chemicals for 
endocrine disrupting properties on animal welfare? 

Overall,  108  respondents  answered  to  this  open  question.  The  results  are  included  in  the  relevant 
section of the Staff Working Document. 

Q22. Are you aware of issues that result from the lack of specific provisions for identifying endocrine 
disruptors in sector-specific legislation for the following areas: 

A  majority of respondents are not aware of issues resulting  from  the lack of specific provisions for 
identifying endocrine disruptors in sector-specific legislation (from 60% to 70%). 

Sector 

Human  and  veterinary  pharmaceuticals  (only  for  effects  on  the 
environment) 

Electrical and electronic equipment 

Other (please specify) 

Medical  devices  and  in  vitro  diagnostic  medical  devices  (only  for 
effects on the environment) 

Waste/recycling 

Food additives 

Toys 

Workers protection 

Detergents 

Fertilisers 

143 

Yes 

No 

39 

80 

40 

33 

42 

42 

43 

45 

47 

46 

46 

81 

65 

81 

81 

78 

77 

78 

75 

74 

 
 
 
 
 
Sector 

Cosmetics 

Food contact materials 

Water 

Yes 

No 

52 

52 

51 

83 

79 

77 

Q23. Are you aware of issues that result from the lack of specific provisions for managing endocrine 
disruptors in sector-specific legislation for the following areas: 

A  majority of respondents are not aware of issues resulting  from  the lack of specific provisions for 
managing endocrine disruptors in sector-specific legislation (from 60% to 67%). 

Sector 

Electrical and electronic equipment 

Food additives 

Fertilisers 

Human  and  veterinary  pharmaceuticals  (only  for  effects  on  the 
environment) 

Yes 

No 

39 

40 

41 

41 

81 

80 

79 

79 

Medical  devices  and  in  vitro  diagnostic  medical  devices  (only  for 
effects on the environment) 

43 

82 

Waste/recycling 

Detergents 

Workers protection 

Toys 

Water 

Cosmetics 

Food contact materials 

Other (please specify) 

42 

44 

45 

45 

49 

53 

51 

32 

78 

76 

77 

75 

76 

81 

76 

72 

Q24.  In  your  view,  on  which  areas  should  market  surveillance  authorities  focus  their  activities  to 
effectively enforce chemical safety of products as regards endocrine disruptors? 

A majority of respondents (80 to 90% of those who expressed an opinion) indicated that authorities 
should focus on market surveillance across all sectors listed. 

144 

 
 
 
 
 
Toys 

Food contact materials 

General chemicals 

Cosmetics 

Human  and  veterinary  pharmaceuticals  (only  for  effects  on  the 
environment) 

Food additives 

Waste/recycling 

Plant Protection Products 

Fertilisers 

Biocidal products 

Detergents 

Medical  devices  and  in  vitro  diagnostic  medical  devices  (only  for 
effects on the environment) 

Electrical and electronic equipment 

Other (please specify) 

Yes  No 

Don't 
know 

88 

99 

93 

92 

75 

90 

80 

87 

74 

88 

76 

71 

65 

27 

10 

12 

13 

13 

11 

14 

13 

16 

14 

17 

16 

15 

15 

13 

44 

37 

40 

37 

52 

40 

50 

39 

49 

38 

48 

53 

61 

63 

  Stakeholder views on efficiency (overall statistics) 

5.6
Benefits  of  regulatory  intervention  include  human  health  and  environmental  protection,  smooth 
functioning  of  the  internal  market,  innovation  and  competitiveness.  Costs  can  be  economic  (time, 
resources)  as  well  as  ethical  (e.g.  use  of  laboratory  animals  for  testing).  Efficiency  considers  the 
benefits in relation to costs. 

Q25.  Has  the  implementation  of  regulatory  requirements  for  endocrine  disruptors  increased  your 
total operating costs?  

Eighty-eight  percent  of  the  concerned  respondents  report  an  increase  of  costs  related  to  regulatory 
requirements  for  endocrine  disruptors.  Forty-eight  percent  consider  the  increased  costs  to  be 
significant. 

Yes, to a significant extent 

Yes, but not to a significant extent 

No 

Not applicable 

145 

Answers 

29 

24 

7 

42 

 
 
 
  
Q26. Has the assessment of substances for endocrine disrupting properties delayed your assessment 
work in other areas of human health or environmental protection? 

Eighty  percent  of  concerned  respondents  report  a  delay  in  their  assessment  work  in  other  areas  of 
human health or environmental protection. Thirty-eight percent consider the delay to be significant. 

Yes, to a significant extent 

Yes, but not to a significant extent 

No 

Not applicable 

Answers 

24 

27 

13 

40 

Q27.  What  is  the  cost  increase  for  your  company  (companies  your  association  is  representing)  to 
comply  with  the  regulatory  requirements  (e.g.  testing,  restriction  or  ban)  specifically  related  to 
endocrine disruptors? 

Few  respondents  replied  to  this  question.  The  type  of  costs  incurring  the  highest  cost  increase  was 
most commonly reported to be related to the provision of test data on endocrine disrupting properties. 

More than 
10% 

Between 5 
and 10% 

Between 
1 and 5% 

Below 
1% 

Don't 
know 

Not 
applicable 

Costs related to the provision of 
test data on endocrine disrupting 
properties 

endocrine 

Cost  to  replace  substances  due 
to 
disrupting 
properties (e.g. as a producer or 
user) 

Investment  in  the  development 
of  new  testing  methodologies 
for 
disrupting 
properties 

endocrine 

Costs  related  to  the  preparation 
of  registration  or  authorisation 
dossiers 
endocrine 
covering 
disrupting properties 

14 

7 

6 

5 

2 

4 

8 

7 

4 

7 

1 

1 

27 

20 

27 

19 

3 

0 

25 

26 

6 

4 

22 

24 

Q28.  What  has  been  the  impact  of  the  provisions  for  endocrine  disruptors  on  the  sector  you 
represent? 

146 

 
 
 
  
 
 
 
More of the respondents expressing an opinion report the impact to be negative rather than positive, 
impacting  productivity  (0  positively,  22  (very)  negatively,  and  9  no  impact),  profitability  (1  very 
positively, 28 (very) negatively, and 3 no impact) and international trade (1 very positively, 25 (very) 
negatively,  and  6  no  impact)  and  to  a  lesser  extent  innovation  (6  (very)  positively,  22  (very) 
negatively, and 14 no impact). 

Q29. Are the costs of the provisions for endocrine disruptor identification and management, for the 
sector(s)  you  operate  in,  justified  and  proportionate  to  the  benefits  accrued  for  society  and  the 
environment? 

Of  those  respondents  expressing  an  opinion,  79%  consider  the  costs  for  endocrine  disruptor 
identification and management justified and proportionate to the benefits accrued for society and the 
environment in their sectors (fully or to some extent). Thirty percent fully agreed with the statement. 

Not at all 

To some extent 

Fully 

Don't know 

Answers 

12 

28 

17 

40 

  Stakeholder views on relevance (overall statistics) 

5.7
Q30. To what extent do you think exposure to endocrine disruptors is contributing to the increase in 
endocrine-related human diseases/disorders, in the EU, in comparison with other factors? 

Sixty-two  percent  of  respondents  who  expressed  an  opinion  think  that  exposure  to  endocrine 
disruptors  is  contributing  to  a  significant  extent  to  the  increase  in  endocrine-related  human 
diseases/disorders in the EU, in comparison with other factors. 

To a significant extent 

Not to a significant extent 

Not at all 

Don't know 

Answers 

75 

40 

6 

46 

Q31. To what extent do you think exposure to endocrine disruptors is contributing to the decrease in 
aquatic and terrestrial biodiversity in the EU, in comparison with other factors? 

Sixty-four  percent  of  respondents  who  expressed  an  opinion  think  that  endocrine  disruptors  are 
contributing to a significant extent to the decrease in aquatic and terrestrial biodiversity in the EU, in 
comparison with other factors. 

Answers 

147 

 
 
 
  
 
 
 
  
To a significant extent 

Not to a significant extent 

Not at all 

Don't know 

70 

36 

3 

57 

Q32. Is the regulatory framework flexible enough to take into account new scientific information and 
methods  in  the  assessment  of  endocrine  disrupting  properties  (e.g.  new  toxicological  tests, 
(bio)monitoring data, (eco)epidemiology)? 

Overall, 84 respondents (53%) think that the regulatory framework is not flexible enough to take into 
account new scientific information and methods in the assessment of endocrine disrupting properties, 
while 73 (47%) think it is. 

Q33. Do you have any further comments on the adequacy of legislation to address societal needs and 
concerns on endocrine disruptors? 

Sixty-four respondents answered this open question. The results are included in the relevant section of 
the Staff Working Document. 

  Stakeholder views on EU-added value (overall statistics) 

5.8
Q34.  Do  you  think  unilateral  action  on  endocrine  disruptors  by  Member  State  Authoritie  is 
justifiable? 

Thirty-two  percent  of  the  respondents  think  it  is  not  justifiable  at  all.  Another  thirty-two  percent 
thinks it is justifiable but should be followed by an EU wide action. Twenty-four percent think that 
this is justifiable in some cases, while 2% consider EDs should not be regulated at EU level. 

This is not justifiable – decisions should be taken at EU level and all citizens of 
the EU should be protected in an equal way, while preserving the integrity of 
the single market.  
This is justifiable, but it should be followed by an EU wide action to preserve 
the integrity of the single market. 
This  is  justifiable  in  some  cases  –  protection  of  human  health  or  the 
environment  is  more  important  than  preserving  the  integrity  of  the  single 
market. 
This is justifiable – endocrine disruptors should not be regulated at EU level. 

Answers 

59 

59 

44 

4 

Q35. Has your organisation been impacted by unilateral actions at national level? 

Of the 66 responses to this question, 30 (48%) consider that their organisation has been impacted by 
unilateral actions at national level, while 33 (52%) do not. 

148 

 
 
 
 
 
  
 
Q36. Do you have any further comments on the added value of regulating endocrine disruptors at EU 
level? 

Seventy-eight  respondents  answered  this  open  question.  The  results  are  included  in  the  relevant 
section of the Staff Working Document. 

  Breakdown of stakeholder views according to stakeholder group 

5.9
For selected questions, the distribution of responses according to stakeholder group was analysed, to 
see if there are notable differences in the views between groups. 

Q2. To what extent does the absence of harmonised criteria pose a problem to a coherent approach 
for the identification of endocrine disruptors? 

Overall,  150  (93%)  of  the  respondents  consider  that  the  absence  of  harmonised  criteria  poses  a 
problem  to  the  identification  of  endocrine  disruptors  across  sectors,  while  11  (7%)  think  it  is  not  a 
problem, the criteria should be sector specific. 

The  breakdown  shows  that  academic/research  institutions,  civil  society  organisations,  public 
authorities  and  trade  unions  are  more  likely  to  see  this  as  a  problem,  compared  with  business 
associations and companies. 

Stakeholder group  No 

society 

Academic/researc
h institution 
Business 
association 
Civil 
organisations 
Company/business 
organisation 
Other 
Public authority 
Trade union 
TOTAL 

Answe
r 
1 

11 

1 

5 

3 
1 
0 
22 

It is an important problem, leading to 
incoherent identification of endocrine 
disruptors across sectors 
13 

33 

25 

21 

15 
32 
11 
150 

It is not a problem, the criteria 
should be sector specific 

0 

3 

1 

5 

0 
2 
0 
11 

Q3. Do you think that the lack of a hazard category covering endocrine disrupting properties in the 
CLP Regulation and/or GHS poses a problem for the coherent identification of endocrine disruptors? 

Opinion is divided on this topic with 94 of the respondents (53%) thinking that this is a problem for 
coherent ED identification, and 83 (47%) thinking it is not. 

The  breakdown  shows  that  academic/research  institutions,  public  authorities  and  trade  unions  are 
more likely to see this as a problem, compared with business associations, companies and civil society 
organisations. 

149 

 
 
 
 
Stakeholder group 
Academic/research 
institution 
Business association 
Civil society organisations 
Company/business 
organisation 
Other 
Public authority 
Trade union 
TOTAL 

No Answer 
0 

No 
7 

Yes 
7 

2 
1 
0 

3 
0 
0 
6 

34 
14 
18 

4 
4 
2 
83 

11 
12 
13 

11 
31 
9 
94 

Q4. Do you think that the lack of a hazard category covering  endocrine disrupting properties in the 
CLP  Regulation  and/or  GHS  poses  a  problem  for  the  coherent  risk  management  of  endocrine 
disruptors? 

Opinion is divided on this topic with 86 of the respondents (51%) thinking that the lack of a hazard 
category is a problem for coherent risk management, and 84 (49%) thinking it is not a problem. 

The  breakdown  shows  that  academic/research  institutions,  public  authorities  and  trade  unions  are 
more likely to see this as a problem, compared with business associations, companies and civil society 
organisations. 

No Answer 

Stakeholder group 
Academic/research institution  1 
Business association 
5 
4 
Civil society organisations 
Company/business organisation  0 
3 
Other 
0 
Public authority 
0 
Trade union 
13 
TOTAL 

No 
4 
31 
16 
20 
4 
7 
2 
84 

Yes 
9 
11 
7 
11 
11 
28 
9 
86 

Q5. Do you think that a category of suspected endocrine disruptor should be introduced? 

Some stakeholders have suggested to classify endocrine disruptors in one of three categories based on 
the level of evidence: i.e. known, presumed or suspected. 

With regard to the need of a category of suspected endocrine disruptors, opinion is again divided with 
89 respondents (53%) being in favour of introducing  a category for suspected endocrine disruptors, 
while 79 (47%) are not in favour. 

The  breakdown  shows  that  academic/research  institutions,  public  authorities,  trade  unions  and  civil 
society  organisations  are  more  likely  to  be  in  favour,  compared  with  business  associations  and 
companies. 

150 

 
 
 
 
 
Stakeholder group 
Academic/research institution 
Business association 
Civil society organisations 
Company/business organisation 
Other 
Public authority 
Trade union 
TOTAL 

No Answer 
0 
3 
3 
1 
6 
2 
0 
15 

No 
5 
38 
1 
22 
8 
4 
1 
79 

Yes 
9 
6 
23 
8 
4 
29 
10 
89 

Q30. To what extent do you think exposure to endocrine disruptors is contributing to the increase in 
endocrine-related human diseases/disorders, in the EU, in comparison with other factors? 

Sixty-two  percent  of  respondents  who  expressed  an  opinion  think  that  exposure  to  endocrine 
disruptors  is  contributing  to  a  significant  extent  to  the  increase  in  endocrine-related  human 
diseases/disorders in the EU, in comparison with other factors. 

To a significant extent 

Not to a significant extent 

Not at all 

Don't know 

Answers 

75 

40 

6 

46 

The  breakdown  shows  that  academic/research  institutions,  public  authorities,  trade  unions  and  civil 
society organisations think that exposure to endocrine disruptors is contributing to a significant extent, 
compared with business associations and companies. 

No 
Answer 

Don't 
know 

Not 
all 

at 

to 

Not 
a 
significant extent 

Academic/research institution 
Business association 
Civil society organisations 
Company/business organisation 

2 
6 
1 
0 

0 
25 
1 
9 

3 
11 
4 
11 

0 
1 
0 
5 

151 

a 

To 
significant 
extent 
9 
4 
21 
6 

 
 
 
 
 
 
 
 
 
 
 
 
No 
Answer 

Don't 
know 

Not 
all 

at 

to 

a 
Not 
significant extent 

Other 
Public authority 
Trade union 
TOTAL 

4 
3 
0 
16 

7 
9 
1 
46 

0 
0 
0 
6 

1 
3 
1 
40 

a 

To 
significant 
extent 
6 
20 
9 
75 

Q31. To what extent do you think exposure to endocrine disruptors is contributing to the decrease in 
aquatic and terrestrial biodiversity in the EU, in comparison with other factors? 

Sixty-four  percent  of  respondents  who  expressed  an  opinion  think  that  endocrine  disruptors  are 
contributing to a significant extent to the decrease in aquatic and terrestrial biodiversity in the EU, in 
comparison with other factors. 

To a significant extent 

Not to a significant extent 

Not at all 

Don't know 

Answers 

70 

36 

3 

57 

The  breakdown  shows  that  academic/research  institutions,  public  authorities,  trade  unions  and  civil 
society organisations think that exposure to endocrine disruptors is contributing to a significant extent, 
compared with business associations and companies. 

No Answer 

Don't 
know 

at 

Not 
all 

society 

Academic/research 
institution 
Business association 
Civil 
organisations 
Company/business 
organisation 
Other 
Public authority 
Trade union 
TOTAL 

2 

6 
1 

0 

5 
3 
0 
17 

0 

1 
0 

2 

0 
0 
0 
3 

3 

14 
5 

17 

6 
10 
2 
57 

152 

a 

a 

to 

Not 
significant 
extent 
0 

To 
significant 
extent 
9 

22 
0 

8 

3 
2 
1 
36 

4 
21 

4 

4 
20 
8 
70 

 
 
 
 
 
 
  
 
 
 
 
6  Outcome of the SME consultation  

  Respondents 

6.1
A  total  of  70  replies  were  received  during  the  SME  consultation.  Eighty-one  percent  of  the 
respondents  have  micro  enterprises  (23),  small  enterprises  (13)  or  medium  enterprises  (19);  four 
percent are self-employed (3), and fifteen percent have large enterprises (10).  
An  analysis  of  the  responses  received  from  large  companies  shows  that  they  are  usually  more 
informed  about  EU  regulations  and  less  affected  by  them,  but  their  contribution  does  not  affect 
significantly  the  overall  results  (less  than  ten  percent).  Consequently,  the  contribution  of  large 
companies was kept in the following analysis. 

Most answers were received from respondents in Romania (27%), Bulgaria (20%), Poland (14%) and 
Portugal  (11%).  The  other  respondents  are  based  in  Italy  (7%),  Greece  (6%),  France  (4%),  Latvia 
(4%), Czech Republic (3%), Belgium (1%) and Spain (1%). 

Sixty-five  respondents  regularly  sell  products  in  all  the  EU  with  the  exception  of  Ireland  and 
Luxembourg. The main countries where products are sold are Romania (26), Germany (17), Bulgaria 
(16), Italy (14), Poland (13) and the United Kingdom (12). 

Most  of  the  respondents  describe  themselves  as  downstream  users  (29),  followed  by  suppliers  (19), 
distributors  (12),  formulators  (9),  importers  (8),  manufacturers  of  chemical  substances  (6)  or  only 
representatives  (2).  Six  respondents  declared  another  role  (e.g.  water  treatment,  security  service 
provider, construction works). 

Respondents are involved in almost  all of the chemical sectors listed with the exception of aerosols 
and  cleaning  services.  The  sectors  most  reported  are  metals  (12),  paints,  inks  and  coatings  (12), 
plastics (11), dyes and pigments (11), and polymers (10). 

  Legislation affecting respondents 

6.2
The five pieces of EU legislation affecting most respondents are: Directive 2008/98/EC on Waste (34 
being familiar with its content vs. 14 being not familiar); REACH Regulation (EC) No 1907/2006 (33 
familiar  vs.  5  not);  Classification,  Labelling  and  Packaging  of  substances  and  mixtures  (EC)  No 
1272/2008 (32 familiar vs. 3 not); Chemical Agents Directive at Work (98/24/EC) (25 familiar vs. 10 
not); and Pregnant Workers Directive (1992/85/EEC) (24 familiar vs. 6 not). 

The five pieces of EU legislation affecting the least respondents are: Veterinary Medicinal Products 
Regulation  ((EU)  2019/6)  (54  not  being  familiar  with  its  content  vs.  6  being  familiar);  Regulation 
(EU) 2017/746 on in vitro Diagnostic Medical Devices (56 not familiar vs. 4); Medicinal Products for 
Humans  (Directive  2001/83/CE)  (54  not  familiar  vs.  4);  Regulation  (EU)  2017/745  on  Medical 
Devices (53 not familiar vs. 6); and Toy Safety Directive 2009/48/EC (53 not familiar vs. 6). 

  Information in the company about endocrine disruptors 

6.3
The  five  sources  of  information  most  used  by  the  respondents  are  safety  data  sheets  from  business 
partners  (43  often  use  this  source  and  7  sometimes);  manufacturers  or  suppliers  of  chemicals  (32 
often,  6  sometimes);  national  authorities  (16  often,  12  sometime);  customers  (16  often,  11 
sometimes); and industry associations (16 often, 10 sometimes). 

The  five  sources  of  information  least  used  by  the  respondents  are:  EU  Agencies  (18  never  use  this 
source and 7 rarely); European Commission (20 never, 9 rarely); authorities at local level (19 never, 8 

153 

 
 
rarely);  authorities  at  regional  level  (19  never,  9  rarely);  and  consultants  including  law  firms  (14 
never, 10 rarely).  

The  respondents  are  divided  in  their  views  on  whether  the  information  at  their  disposal  helps  their 
company to comply with legal requirements for endocrine disruptors, with 12 replying not at all and 
25 to a small extent; 23 to a large extent and 8 completely. 

One respondent referred to the use of scientific literature, while another made use of several databases 
(Toxnet, ACGIH, HHS, AIDII). 

  SME views on coherence 

6.4
Twenty seven percent of respondents consider the lack of horizontal criteria to be problematic, while 
22% do not consider it a problem. The remainder either did not know or did not reply. In the free text 
comments,  respondents  highlighted  problems  in  the  following  areas:  non-stick  coatings,  the  food 
sector generally, stabilised aqueous mixtures for different industrial sectors, as well as perfumery and 
cosmetics.  One respondent  who did  not consider it  a problem said that EDs  can be identified  using 
various information sources (ECHA, European Council of Paintings), noting that the real problem is 
the risk assessment. 

The lack of a hazard category covering endocrine disrupting properties in the Classification, Labelling 
and  Packaging  (CLP)  Regulation  and/or  GHS  poses  a  problem  for  the  coherent  identification  of 
endocrine disruptors according to 82% of respondents, and also causes a problem for the coherent risk 
management of endocrine disruptors according to 84% of respondents. 

Sixteen percent of the respondents reported being aware of inconsistencies in the way chemicals are 
addressed with regard to endocrine disrupting properties across regulated areas in the EU. In the free 
text comments, respondents cited inconsistencies related to bisphenol A, phthalates, and water-based 
textile auxiliaries vs biocidal products/pesticides. 

Differences in the ways EDs are regulated between the EU and other jurisdictions (e.g. USA, China) 
affect five respondents to a significant extent, ten to some extent, five to a minor extent, sixteen not at 
all,  while  thirty-four  respondents  indicated  that  they  did  not  know.  In  the  free  text  comments, 
respondents commented on unfair competition (e.g. toys) and the fact that some suppliers are selling 
raw materials to a less restrictive market, accompanied by an increase in the costs and availability of 
products in Europe.   

  SME views on effectiveness 

6.5
In  general,  respondents  consider  the  regulatory  process  to  identify  and  control  chemicals  with 
endocrine  disrupting  properties  to  be  effective  in  protecting  people  and  wildlife,  in  improving  the 
functioning of the internal market, and enhancing competitiveness and innovation. This can be seen in 
Figure 13.3 since respondents more often agree than disagree.  

154 

 
 
Figure 13.3. SME views on effectiveness 

  SME views on efficiency 

6.6
Out  of 70 respondents, the need  to implement  regulatory requirements for endocrine disruptors was 
reported to increase total operating costs by 25 respondents (3 to a significant extent, and 22 not to a 
significant extent), whereas 12 respondents reported no effect on operating costs. For the remaining 
33 respondents, this question was either not applicable (30) or no answer was provided (3). Costs are 
related  to:  a)  the  replacement  of  substances  (21  respondents);  b)  the  preparation  of  registration  or 
authorisation  dossiers  (14  respondents);  c)  the  provision  of  test  data  (14  respondents);  and  d)  the 
development of new testing methodologies (13 respondents). 

In  terms  of  the  perceived  impact  of  the  provisions  for  endocrine  disruptors  on  innovation, 
productivity, profitability and international trade within their sectors (Figure 13.4), few respondents 
(between  1  to  6)  regarded  the  impact  as  negative  or  very  negative  and  another  minority  (7  to  10) 
considered the impact as positive or very positive. The rest considered there was no impact (8 to 13), 
did not answer or did not know (14 to 17), or considered the question not applicable to them (26 to 
32). 

155 

 
 
 
 
 
Figure 13.4. SME views on efficiency 

The  costs  of  the  provisions  for  ED  identification  and  management  in  each  respondent’s  respective 
business sector were considered justified and proportionate for the benefits accrued by 23 respondents 
(3 fully and 20 to some extent), not at all justified or proportionate by 8 respondents, while 38 did not 
know. 

  SME views on EU added value 

6.7
In  some  instances,  Member  State  authorities  have  taken  unilateral  action  on  endocrine  disruptors, 
before  the  EU  made  a  decision  on  them.  For  example,  in  October  2012,  the  French  authorities 
introduced  a  ban  of  Bisphenol  A  in  all  food  contact  materials,  applicable  from  July  2015.  One 
respondent  commented  on  the  need  to  treat  products  destined  for  France  as  a  special  case.  Another 
expressed concerns about the implications of a Scandinavian SIN list. 

Ninety-six percent of the respondents reported that unilateral Member State actions did not affect their 
company. 

  Additional comments made by SMEs 

6.8
In  the  free  text  field  for  the  final  question  (Q19;  “Please  provide  any  additional  comment  or 
suggestion  that  you  consider  relevant  for  the  ED  Fitness  Check”),  respondents  raised  the  following 
points: 

  Need  to  align  legislation  for  cosmetics,  chemicals,  medical  and  surgical  products  and 

detergents 

  Difficulty in moving from hazard identification to risk management. 
  Difficulty  in  establishing  a  safe  exposure  threshold:  “  there  is  a  big  difference  between 
injecting  an  isothiazolinone  into  a  living  being,  and  the  exposure  of  an  individual  to  a  dry 
painting containing 0.00015%.” 

  Elimination of new ED substances is complicated and costly.  

156 

 
 
 
 
  The precautionary principle should be applied based on scientific evidence. 
  Need for better information and tools (e.g. databases) for SMEs 
  Need for SME support and private-public co-financing programmes 

One respondent made reference to the fact that water companies do not seek information on endocrine 
disruptors, because the Drinking Water Directive does not impose an obligation to do so. It was also 
noted  that  some  larger  water  companies  are  conducting  research,  such  as  into  the  feasibility  of  an 
effective extended producer responsibility (EPR) scheme on products that release micropollutants and 
microplastics into the aquatic environment during their life cycle120. 

Another  respondent  proposed  to  replace  the  plastic  packaging  materials  with  glass,  and  to  replace 
juices  containing  dyes  and  synthetic  chemicals  with  natural  ones,  which  should  also  be  favourably 
priced. 

120http://www.eureau.org/resources/publications/4380-deloitte-eureau-report-extended-producer-responsibility-
modules-1-2-3/file 

157 

 
 
 
 
 
 
                                                      
Annex 3.  Methodology 

1  Summary 
The methodology for the Fitness Check was developed by the JRC and agreed with the Interservice 
Steering  Group.    The  methodology  identified  the  legislation  considered  to  be  in  the  scope  of  the 
Fitness  Check,  and  a  series  of  questions  were  formulated  to  guide  the  interpretation  of  the  five 
evaluation criteria, namely coherence, effectiveness, efficiency, relevance and EU-added value. 

Four  main  evidence  streams  were  generated  to  inform  the  findings:  a)  mapping  of  regulatory 
provisions related to the identification or risk management of endocrine disruptors; b) review of key 
policy and scientific documents; c) chemical specific case studies to illustrate the interplay between 
different  pieces  of  legislation;  and  d)  the  results  of  consultations  with  the  public,  stakeholders  and 
SMEs. 

2  Workflow 
The  horizontal  nature  of  the  Fitness  Check  required  a  broad  scope,  covering  many  legal  acts 
addressing  chemicals  that  are  relevant  to  human  health  and  the  environment.  For  much  of  the 
chemicals acquis, Fitness Checks and other 'Better Regulation' activities addressing specific pieces of 
legislation had been completed or are ongoing.  

To  make  optimal  use  of  the  extensive  work  already  completed  under  regulatory  review  activities,  a 
stepwise approach was adopted (Figure 14.1). In the first phase (blue), a preliminary analysis of the 
current situation defined the scope of the Fitness Check and led to the formulation of the evaluation 
questions. In the second phase (orange), factual evidence was extracted from existing fitness checks, 
in-scope legislation and relevant literature reviews. Additional information relating to the evaluation 
questions was sought in the third phase (green) through a series of consultations.  

Figure 14.1 Workflow of the Fitness Check 

158 

 
 
 
 
3  Preliminary analysis of current situation 

  Questionnaire to policy DGs 

3.1
A  questionnaire  was  prepared  by  JRC  to  solicit  initial  inputs  from  policy  DGs  (ENV,  GROW  and 
SANTE)  with  experience  in  managing  ED-relevant  legislation  on  the  current  policy  and  regulatory 
state  of  play  and  the  practical  implementation  of  policy  and  legal  instruments.  Information  was 
collected  on  the  specific  and  generic  provisions  for  ED  identification,  risk  assessment  and  risk 
management, and on the chemicals that have been regulated based on identification as ED across the 
different pieces of (in-scope) legislation. This input informed the definition of the scope of the FC and 
the formulation of evaluation questions. It also provided an initial basis for a systematic mapping of 
provisions in the different pieces of legislation that are relevant for the identification, assessment and 
regulation of EDs. 

  Identification of Regulatory Reviews/Better Regulation activities  

3.2
The evaluation of the 7th Environment Action Programme mentions ED risks as an emerging concern. 
ED-related issues are addressed at different levels of detail in recent Fitness Checks and evaluations 
of  chemical  legislation,  including  the  REACH  REFIT  evaluation121,  the  REACH  Review  on  the 
authorisation  route  of  substances  with  endocrine  disrupting  properties  according  to  REACH  Art. 
138(7),  the  Fitness  Check  of  the  chemicals  legislation  other  than  REACH  and  the  review  of  the 
legislation on cosmetics with regard to endocrine disrupting substances. Among legislation regulating 
downstream uses of chemicals in products, the evaluation of the legislation on food contact materials 
and the evaluation of the legislation on toy safety were also considered relevant to this FC. Among 
pieces  of  environmental  legislation,  the  Fitness  Check  of  the  water  legislation  was  considered  for 
potentially ED-relevant aspects. 

Also relevant was Annex 9 of the impact assessment on the definition of criteria for identifying EDs 
in  the  context  of  the  Plant  Protection  Products  Regulation  and  Biocidal  Products  Regulation.  This 
provides a multi criteria analysis of impacts (on health, environment etc.) based on a scientific review 
of the evidence linking endocrine disrupting chemicals to hormone-related diseases and the estimated 
related costs to society attributed to exposure to EDs.   

  Definition of scope 

3.3
On  the  basis  of  the  mandate  of  the  FC  described  in  the  Commission  Communication  “Towards  a 
comprehensive  EU  framework  on  endocrine  disruptors”,  in-scope  legislation  was  defined  as 
legislation  including  provisions  for  the  identification,  hazard  assessment,  risk  assessment  or  risk 
management of chemicals with endocrine disrupting properties for human health and the environment. 
In-scope legislation includes: 

a)  Legislation  that  specifically  identifies  EDs  with  regulatory  consequences  following  such 
identification (ED-specific provisions) 
b) Legislation that does not specifically identify EDs but regulates chemicals according to the risk 
identified and which may include adverse effects on the endocrine system (general provisions) 
c) Legislation which is interconnected with a) or b) with implications for the identification, hazard 
assessment, risk assessment or risk management of chemicals  

121Second REACH review. COM(2018) 116 and SWD(2018) 58 

159 

 
 
                                                      
 
Based on these criteria legislation considered in scope is listed in Table 14.1. 

Table 14.1 Legislation in scope for this Fitness Check 

Legislation 
Plant Protection Products Regulation (EC) No 1107/2009 

Commission Regulation (EU) 2018/605 of 19 April 2018 amending Annex II to Regulation (EC) 
No  1107/2009  by  setting  out  scientific  criteria  for  the  determination  of  endocrine  disrupting 
properties (plant protection products) 
Regulation  (EU)  No 283/2013  setting  out  the  data  requirements  for  active  substances  in 
accordance with Regulation (EC) No 1107/2009 

Maximum Residue Levels of Pesticides Regulation (EC) No 396/2005 
Biocidal Products Regulation (EU) No 528/2012 

Commission  Delegated  Regulation  (EU)  2017/2100  of  4  September  2017  setting  out  scientific 
criteria for the determination of endocrine-disrupting properties pursuant to Regulation (EU) No 
528/2012 of the European Parliament and Council (biocidal products) 

REACH Regulation (EC) No 1907/2006 
CLP: Classification, Labelling and Packaging of substances and mixtures (EC) No 1272/2008 
Persistent Organic Pollutants Regulation (EU) 2019/1021 
Food contact materials legislation Regulation (EC) No 1935/2004*  
Contaminants in food Regulation (EEC) No 315/93 and in feed Directive 2002/32/EC 
Food Additives Regulation (EC) No 1333/2008  
Cosmetic Products Regulation (EC) No 1223/2009 
Medical Devices Regulation (EU) 2017/745  
In Vitro Diagnostic Medical Devices Regulation (EU) 2017/746 
Toy Safety Directive 2009/48/EC 
Fertilising Products Regulation (EU) 2019/1009 
Detergents Regulation (EC) No 648/2004 
Medicinal Products for Human Directive 2001/83/EC ** 
Coverage here limited to unintended exposure via the environment (see also 3.10) 
Veterinary Medicinal Products Regulation (EU) 2019/6 **  
Coverage here limited to unintended exposure via the environment (see also 3.10) 
General Product Safety Directive 2001/95/EC 
Water Framework Directive 2000/60/EC  
Priority substances Directive 2013/39/EU 
Drinking Water Directive 98/83/EC  
Groundwater Directive 2006/118/EC 
Marine Strategy Framework Directive 2008/56/EC 
Urban Waste Water Directive 91/271/EEC 
Chemical Agents at Work Directive 98/24/EC 
Carcinogens and Mutagens at Work Directive 2004/37/EC 
Pregnant Workers Directive 92/85/EEC 
Young People at Work Directive 94/33/EC 
Waste Directive 2008/98/EC  

Commission Decision 2014/955/EU on the list of waste pursuant to Directive 2008/98/EC 

160 

 
 
 
Legislation 
Restriction of the use of certain hazardous substances in electrical and electronic equipment Directive 
2011/65/EU 
Industrial emissions (integrated pollution prevention and control) Directive 2010/75/EU 
Seveso-III-Directive 2012/18/EU 
Ambient Air Quality and Cleaner Air for Europe Directive 2008/50/EC 
EU Ecolabel Regulation (EC) No 66/2010  
*Evaluation ongoing 
**EU Pharmaceuticals Strategy is under development 

  Formulation of Fitness Check questions 

3.4
Based on the preliminary analysis of the current situation, evaluation questions were drafted by JRC, 
with emphasis on coherence issues across the different in-scope regulatory instruments in Table 14.1. 
The questions were refined and endorsed by the inter-service steering group (ISSG).  

To apply the FC questions, it was necessary to establish a baseline for comparison. When a temporal 
reference  needs  to  be  established,  the  baseline  is  the  situation  with  no  specific  provisions  in  EU 
legislation, corresponding to the year of adoption of the first strategy on endocrine disruptors (1999). 
The  evaluation  questions  relate  to  the  specific  policy  interventions  or  non-interventions  across  the 
different regulatory sectors from 1999 to date (e.g. implementation of REACH or the establishment of 
ED criteria for pesticides and biocides). Other points of reference, such as non-EU jurisdictions, were 
considered when appropriate. 

4  Extraction and review of available evidence  

  Mapping of provisions 

4.1
The  FC  required  analysis  of  the  provisions  that  are  relevant  for  the  identification,  assessment  and 
management  of  EDs  across  in-scope  legislation.  ED-specific  and  general  provisions  on  hazard 
assessment,  risk  assessment  and  management  were  mapped  with  inputs  from  policy  DGs  on  the 
respective areas of competence. The mapping exercise identified the main regulatory instruments and 
the relevant implementing measures. Legislative instruments are to some extent interconnected. This 
is  the  case  for  substances  with  endocrine  disrupting  properties  regulated  both  via  the  horizontal 
chemical  legislation  (e.g.  REACH  &  CLP  Regulations)  and  by  sectorial  legislation  (e.g.  cosmetic 
products,  toys,  food  contact  materials).  The  objective  of  this  step  was  thus  to  provide  a  complete 
picture of how substances with endocrine disrupting properties are regulated in the EU, illustrating the 
current logic of legislative intervention across regulated sectors.  

4.2

  Policy and scientific sources of evidence  

Regulatory reviews/Better Regulation activities  

The outcome of recent and ongoing Better Regulation activities (Section 2.1.2), was expected to be a 
major  source  of  information,  together  with  the  mapping  of  provisions  (Section  2.2.1).  Factual 
evidence was therefore extracted and synthesised to help address the evaluation questions.    

EU institutions and stakeholder reviews 

161 

 
 
 
Numerous scientific studies and reports have been published in recent years. A selection of studies of 
policy  and  scientific  relevance  were  identified  and  screened  for  relevant  input  to  the  evaluation 
questions.  These  studies  (cited  throughout  this  document)  were  studies  by  EU  institutions;  studies 
commissioned by EU institutions, national and international organisations; and studies by stakeholder 
organisations.  

  Evidence base and limitations 

4.3
Details on the sources of evidence in previous Commission fitness checks and evaluations, including 
their limitations, are given in the respective reports. 

Reviews  in  the  scientific  literature  were  used  where  they  refer  to  general  scientific  background. 
Scientific studies and stakeholder reports were only used to refer to an important stakeholder point of 
view. The citation of these sources does not necessarily imply that the Commission agrees with the 
findings, or shares the same views. 

  Case studies 

4.4
Case  studies  were  developed  for  specific  chemicals,  which  are  regulated  under  different  and 
interconnected  legislative  instruments,  with  the  aim  to  provide  representative  examples  illustrating 
how EDs are identified, assessed and managed across legislation for their effects on human health and 
the  environment.  Any  differences  or  inconsistencies  were  analysed  with  inputs  from  the  ISSG.  The 
case studies were used as an additional source of evidence for the evaluation questions.  

Substances selected for the case studies: 

  3-Benzylidene  camphor  (3-BC;  under  assessment  under  REACH  and  the  Cosmetics 

Regulation; endocrine disruptor with human health and environmental concern) 

  Diethylhexyl  phthalate  (DEHP;  regulated  under  several  pieces  of  legislation:  REACH, 
cosmetic  products,  medical  devices,  food  contact  materials,  toys,  Water  Framework 
Directive; endocrine disruptor with human health and environmental concern): 

  Nonylphenol  (NP;  regulated  under  REACH  (covering  many  sectors:  detergents,  biocides, 
plant protection products, cosmetic products, medical devices), Water Framework Directive; 
endocrine disruptor with environmental concern) 

  Evidence base and limitations 

4.5
The  main  criterion  for  selecting  case  studies  was  that  the  substances  should  be  identified  as  EDs, 
relevant to more than one policy area, thereby enabling an analysis of the coherence of the assessment 
and risk management approaches applied. The number of SVHCs with endocrine disrupting properties 
under REACH were limited at the time of selection to 14, with several being from the same chemical 
family.  DEHP,  3-BC  and  nonylphenols  and  their  ethoxylates  are  regulated  by  various  pieces  of 
analysed  legislation,  including  the  ones  specifically  mentioned  in  the  FC  mandate.  DEHP  and 
nonylphenols  are  representative  of  two  main  groups  of  substances  which  have  been  formally 
identified  as  EDs  (phthalates,  alkylphenols).  Thus,  case  studies  were  chosen  to  be  as  representative 
and informative as possible. 

  Economic case studies 

4.6
Two  economic  case  studies  were  also  carried  out  to  explore  possible  associations  between  the 
implementation of risk management measures on selected chemicals and trade flows, both within the 
EU and between the EU and non-EU countries (Canzian et al, 2020).  

162 

 
 
The  first  case  study  considered  four  low  molecular  weight  (LMW)  phthalates  commonly  used  as 
plasticisers  (DEHP,  DBP,  BBP  and  DIBP),  which  have  been  inter  alia  subjected  to  a  series  of 
restrictions  since  1999.  The  second  case  study  focused  on  3-Benzylidene  Camphor  (3-BC),  a  UV 
filter  used  in  sunscreen  products  and  other  whitening  skin  care  cosmetic  products,  which  has  been 
subject  to  a  ban  under  the  Cosmetic  Products  Regulation  since  2015  and  was  identified  as  SVHC 
under REACH in 2018.  

The  approach  applied  the  “gravity  model”  including  the  Difference-in-difference  (DiD)  approach. 
Gravity  models  relate  the  magnitude  of  trade  between  countries  to  a  series  of  country-specific 
characteristics  -  notably,  their  economic  size  and  level  of  economic  development  -  and  to  factors 
stimulating  or  discouraging  the  movement  of  products  between  countries.  The  latter  include 
transportation  costs,  usually  proxied  by  the  presence  or  absence  of  a  shared  land  border  and  by 
geographic  distance,  and  informal  and  formal  trade  barriers,  often  proxied  by  the  existence  of  a 
common  language  and  by the  presence  of  free  trade  agreements.  Among  other  applications,  gravity 
models  have  been  used  to  evaluate  trade  under  Non-Tariff  Measures,  such  as  the  above-mentioned 
restrictions on chemicals. 

The Difference-in-difference (DiD) approach is an econometric method for non-experimental causal 
inference.  

In this study, it was used to compare the change in trade flows before and after the intervention of a 
treated group of units/countries relative to the change in trade flows before and after the intervention 
of  a  control  group  of  units/countries  considered  to  be  a  suitable  counterfactual.  The  DiD  approach 
aims to account for confounding variables. 

As inputs to the methodology, worldwide import trade data were retrieved from the United Nations 
Commodity Trade Statistics Database (UN COMTRADE) for the years running from 1995 to 2018. 
Additionally, data were collected for control variables that are typically included in standard gravity 
models,  such  as  the  GDP,  the  size  and  the  population  levels  of  both  countries,  the  geographical 
distance  between  them,  whether  they  share  a  common  language  or  (past  or  current)  colonial  ties. 
These  variables  were  collected  from  CEPII  (Centre  d'Études  Prospectives  et  d'Informations 
Internationales) and the World Bank. 

In the case study on LMW phthalates, the analysis of trade flows focused on plasticisers, the actual 
material subject to the intervention. For the analysis of intra-EU trade flows, the control commodity 
was polyethylene polymer (PET), the most commonly used plastic not containing plasticisers.  

In  the  case  study on  3-BC,  the  analysis  of  trade  flows  focused  on  the  commodity  of  “cosmetic  and 
toilet preparations”, while the control commodity for the analysis of intra-EU trade flows was “oral 
and  dental  hygiene  preparations”.  The  rationale  for  selecting  the  control  commodity  was  that  it 
belongs  to  the  same  broader  category  as  the  treated  good  (cosmetic  and  toilet  preparations)  but 
excludes products containing UV filters. 

To compare EU vs non-EU trade flows, there was no need for a control commodity, since the trade 
flows of the case commodity could be compared directly. 

The  use  of  the  gravity  model  with  difference-in-differences  is  a  well-established  econometric 
approach. The major source of uncertainty in these case studies was therefore linked to the nature of 
the  input  data.  Since  the  trade  flow  data  in  the  UN  Comtrade  database  relate  to  baskets  of 
commodities, rather than the specific chemicals of interest, it was necessary to choose proxies for the 

163 

 
 
chemicals of interest (namely plasticisers for LMW phthalates, and cosmetic/toilet preparations for 3-
BC). The actual market share of the chemical of interest in the chosen commodities was not known.  

Thus, the two case studies illustrated some of the challenges in using economic analysis to identify the 
trade impacts of regulatory interventions. They also point to the need for higher resolution trade data, 
closer to the chemical and commodity of interest, as well as information on market shares. 

5  Consultation activities 

  External consultation activities 

5.1
Consultation activities were carried out to gather inputs from a broad range of stakeholder  groups as 
well as citizens to ensure that views from all interested parties were considered in the evaluation. The 
consultation  activities  relied  primarily  on  the  results  of  three  surveys  aimed  at  the  general  public, 
stakeholders and SMEs. The targeted stakeholder consultations were also used to solicit information 
from companies on financial and other consequences of implementing ED-related legislation. Further 
information on the approach and findings is given in Annex 2. 

  Evidence base and limitations 

5.2
The  consultation  activities  were  used  as  an  additional  source  of  evidence,  recognising  that  survey 
results  are  associated  with  an  inevitable  bias  towards  those  who  have  an  interest  in  responding. 
Therefore, the results in Annex 2 are presented in terms of the numbers and percentages of responses 
received. It is not implied that these statistics are representative of the population being surveyed. 

In the public consultation,  a total of 474 respondents provided an answer, of which 90% were EU 
citizens, 3% were academic/research institutions and 2% non-governmental organisations. Analysis of 
the survey results for attempts to bias the conclusions revealed no obvious re-occurring pattern across 
the answers. Ten percent of the responses were from non-citizens, but these showed no alignment to a 
common position and did not influence significantly the results.   

In  the  stakeholder  consultation,  183  responses  were  received.  The  respondents  were  businesses, 
public authorities, academics, research organisations, and civil society organisations.  

In  the  survey  targeting  micro,  small  and  medium-sized  enterprises  (SMEs),  responses  were 
received from just 70 SMEs.  In this case, while individual free responses were informative of some 
SME views, the sample size was too small to draw firm conclusions. 

164 

 
 
 
 
Annex  4.    Mapping  of  provisions  and  regulatory  processes  for 

identifying and managing Endocrine Disruptors 

Table of Contents 

1  Biocidal Products ............................................................... Error! Bookmark not defined. 

2 

Plant protection products and residues .............................. Error! Bookmark not defined. 

3  REACH .............................................................................. Error! Bookmark not defined. 

4  Classification, Labelling and Packaging (CLP) ................ Error! Bookmark not defined. 

5 

POPs Regulation ................................................................ Error! Bookmark not defined. 

6  Toys ................................................................................... Error! Bookmark not defined. 

7 

Food legislation ................................................................. Error! Bookmark not defined. 

7.1 

Food Contact Materials .............................................. Error! Bookmark not defined. 

7.2  Contaminants in food ................................................. Error! Bookmark not defined. 

7.3 

Food additives ............................................................ Error! Bookmark not defined. 

8  Cosmetic Products ............................................................. Error! Bookmark not defined. 

9  Medical devices and in vitro diagnostics ........................... Error! Bookmark not defined. 

10  Human and veterinary medicines ...................................... Error! Bookmark not defined. 

11  Occupational Safety and Health legislation (OSH) ........... Error! Bookmark not defined. 

12  Water ................................................................................. Error! Bookmark not defined. 

13  Chemical-product-waste interface ..................................... Error! Bookmark not defined. 

14  Other in-scope legislation .................................................. Error! Bookmark not defined. 

15  WTO rules ......................................................................... Error! Bookmark not defined. 

16  References ......................................................................... Error! Bookmark not defined. 

165 

 
 
 
 
 
 
 
1  Biocidal Products 
The Biocidal Products Regulation ((EU) No 528/2012) aims to improve the functioning of the internal 
market through the harmonisation of the rules on the marketing and use of biocidal products, whilst 
ensuring  a  high  level  of  protection  of  both  human  and  animal  health  and  the  environment.  The 
provisions of this Regulation are underpinned by the precautionary principle and pay attention to the 
protection of vulnerable groups. 

All biocidal products require an authorisation before they can be placed on the market, and the active 
substances  contained  in  the  biocidal  product  must  have  been  previously  approved.  The  approval  of 
active substances takes place at EU level and the subsequent authorisation of the biocidal products at 
Member  State  level  (with  possible  extension  to  other  Member  States  by  mutual  recognition).  An 
authorisation of products at EU level (Union authorisation) is also possible. 

The  Biocidal  Products  Regulation  is  interlinked  with  other  regulations  and  directives  including: 
REACH,  CLP,  Chemical  Agents  at  Work  Directive,  Carcinogens  and  Mutagens  at  Work  Directive, 
POPs Regulation, Drinking Water Directive, and the Water Framework Directive.  

This  Regulation  contains  specific  provisions  for  substances  with  endocrine  disrupting  properties. 
Regarding the identification of EDs, the Regulation states that “no later than 13 December 2013, the 
Commission shall adopt delegated acts in accordance with Article 83 specifying scientific criteria for 
the  determination  of  endocrine-disrupting  properties”.  The  Commission  conducted  a  public 
consultation  and  an  impact  assessment  evaluating  different  options  as  included  in  the  roadmap  for 
supporting  the  process  of  developing  the  criteria.  In  addition,  the  regulatory  process  for  setting  the 
scientific criteria for the determination of endocrine disrupting properties under the Biocidal Products 
Regulation and the Plant Protection Products Regulation (EC) 1107/2009 was coordinated and aligned 
as  far  as  possible.  The  Delegated  Regulation  setting  out  scientific  criteria  for  the  determination  of 
endocrine-disrupting  properties  ((EU)  2017/2100)  was  adopted  by  the  Commission  in  September 
2017 and entered into application in June 2018. The criteria are based on the IPCS/WHO definition of 
an endocrine disrupter, and state that: 

“A  substance  shall  be  considered  as  having  endocrine  disrupting  properties  that  may  cause  adverse 
effect [in humans]/[on non-target organisms] if, based on points (a) to (d) of point (2), it is a substance 
that meets all of the following criteria, unless there is evidence demonstrating that the adverse effects 
identified are not relevant [to humans]/[at the (sub)population level for non-target organisms]:  

(a) it shows an adverse effect [in an intact organism or its progeny]/[in non-target organisms], which 
is  a  change  in  the  morphology,  physiology,  growth,  development,  reproduction  or  life  span  of  an 
organism,  system  or  (sub)population  that  results  in  an  impairment  of  functional  capacity,  an 
impairment of the capacity to compensate for additional stress or an increase in susceptibility to other 
influences;   

(b) it has an endocrine mode of action, i.e. it alters the function(s) of the endocrine system;   

(c) the adverse effect is a consequence of the endocrine mode of action” 

Member  State  competent  authorities  evaluate  the  dossiers  submitted  by  applicants  in  view  of  the 
approval (or renewal of approval) of active substances, and draft a Competent Authority Report which 
is sent to ECHA for peer-review by the Agency and the other Member States. The Biocidal Products 
Committee (on behalf of ECHA) prepares an opinion which is the basis for decision on the approval 
by the European Commission, following a vote in the Standing Committee on Biocidal Products. The 

166 

 
 
Endocrine  Disruptor  Expert  Group  set  up  by  ECHA  can  be  consulted  for  scientific  advice,  by  the 
Competent Authority during its evaluation, or by the Biocidal Products Committee. 

The  guidance  for  the  identification  of  endocrine  disruptors  in  the  context  of  Regulations  (EU)  No 
528/2012  (and  (EC)  No  1107/2009)  (developed  jointly  by  ECHA  and  EFSA  and  published  in  June 
2018; (ECHA et al., 2018)), describes how to perform hazard identification for endocrine-disrupting 
properties.  As  required  by  the  criteria,  the  identification  is  based  on  the  gathering,  evaluation  and 
consideration of all relevant information for the assessment, mode of action analysis, and application 
of a weight of evidence approach, to establish whether the ED criteria are fulfilled. 

The  Biocidal  Products  Regulation  states  that  active  substances  which  are  considered  as  having 
endocrine-disrupting  properties  that  may  cause  adverse  effects  shall  not  be  approved.  Derogations 
exist if (a) the risk to humans, animals or the environment from exposure to the active substance in a 
biocidal product, under realistic worst case conditions of use, is negligible, (b) it is shown by evidence 
that the active substance is essential to prevent or control a serious danger to human health, animal 
health  or  the  environment;  or  (c)  not  approving  the  active  substance  would  have  a  disproportionate 
negative  impact  on  society  when  compared  with  the  risk  to  human  health,  animal  health  or  the 
environment arising from the use of the substance. However, the use of a biocidal product containing 
such active substances shall be subject to appropriate risk-mitigation measures to ensure that exposure 
of humans, animals and the environment is minimised. Moreover, such biocidal products shall not be 
authorised  for  making  available  on  the  market  for  use  by  the  general  public.  They  can  also  not  be 
authorised via a Union authorisation. 

The information requirements for active substances and biocidal products are listed in Annexes II and 
III to the Regulation. Currently, specific information requirements for endocrine disrupting properties 
are not part of the core data set (they are “additional” information requirements). However, applicants 
need  to  submit  the  relevant  data  to  determine  whether  a  substance  can  be  considered  to  have  ED 
properties as a competent authority shall have all the necessary information to carry out the evaluation 
of  a  substance.  Studies  shall  be  required  in  accordance  with  the  Guidance  for  the  identification  of 
endocrine disruptors in the context of Regulations (EU) No 528/2012 and (EC) No 1107/2009, among 
others,  to  elucidate  the  mode/mechanism  of  action,  and  provide  sufficient  evidence  for  relevant 
adverse effects. The guidance referred to above clearly states that the Test guidelines (TGs) are able to 
identify only certain endocrine modes of action related to the EATS pathways but that on a case-by-
case basis specific investigations of evidence of other types of endocrine activity (non-EATS) may be 
requested.  Although  these  TGs  are  not  specifically  designed  to  allow  for  the  identification  of  EDs 
they do permit the identification of possibly endocrine-related adverse effects. The guidance is based 
on  the  OECD  GD150  (OECD,  2018)122  and  the  test  guidelines  within  the  OECD  Conceptual 
Framework (CF) from which a stepwise testing strategy is built to identify substances acting through 
EATS  modes  of  action,  in  many  cases  requiring  the  generation  of  further  data  to  either  confirm  or 

122This Guidance Document, originally published in 2012 and updated in 2018, is intended to provide guidance 
for evaluating chemicals for endocrine disrupting properties using standardised test guidelines. Specific 
objectives include providing a description of the OECD conceptual framework for evaluating chemicals for 
endocrine disruption, background on the standardised test methods used, and guidance for interpreting the 
outcome of individual tests. The Guidance Document is focused primarily on endocrine modalities included in 
the conceptual framework; estrogen, androgen, and thyroid mediated endocrine disruption and chemicals that 
interfere with steroidogenesis. 

167 

 
 
                                                      
 
remove  concerns  for  endocrine  disrupting  properties.  A  (systematic)  review  of  the  literature  is  also 
required to identify relevant studies from the published scientific literature. 

Data requirements in Annex II and III are currently being adapted to scientific and technical progress 
including data that are relevant for the determination of ED properties. 

2  Plant Protection Products and residues 
The  purpose  of  the  Plant  Protection  Products  Regulation  ((EC)  No  1107/2009)  is  to  ensure  a  high 
level  of  protection  of  both  human  and  animal  health  and  the  environment  and  to  improve  the 
functioning of the internal market through the harmonisation of the rules on the placing on the market 
of  plant  protection  products,  while  improving  agricultural  production.  The  provisions  of  this 
Regulation are underpinned by the precautionary principle. 

The  Plant  Protection  Products  Regulation  is  interlinked  with  other  Regulations  and  Directives 
including:  REACH,  CLP,  Chemical  Agents  Directive  at  Work,  Carcinogens  and  Mutagens  at  work 
Directive, POPs Regulation, Drinking Water Directive, Water Framework Directive, and the Directive 
on the Sustainable Use of Pesticides. 

The Regulation on maximum residue levels (MRLs) of pesticides ((EC) No 396/2005), ensures a high 
level  of  consumer  protection  and  harmonised  provisions  relating  to  maximum  levels  of  pesticide 
residues in or on food and feed of plant and animal origin. 

Similar  to  the  Biocidal  Products  Regulation,  the  Plant  Protection  Products  Regulation  contains 
specific  provisions  for  substances  with  endocrine  disrupting  properties.  Regarding  the  identification 
of  EDs,  specific  scientific  criteria  for  the  determination  of  endocrine  disrupting  properties  were 
introduced  into  the  PPPR  by  the  Regulation  (EU)  2018/605.  These  criteria  are  applicable  since 
November 2018.  

The criteria are almost identical to those applicable to the biocidal products (see above). A guidance 
for the identification of endocrine disruptors in the context of Regulations (EC) No 1107/2009 (and 
(EU) No 528/2012) is available (published in June 2018, see above under biocides for more details). 

The  procedure  to  approve  a  substance  starts  with  the  submission  by  an  applicant  of  a  dossier  to  a 
Rapporteur  Member  State,  who  prepares  an  initial  risk  assessment  and  a  Draft  Assessment  Report 
which EFSA, together with the Member States, peer reviews. EFSA then adopts conclusions and the 
Commission prepares a review report and a draft Regulation on the approval (or renewal of approval), 
which is presented to the Standing Committee on Plants, Animals, Food and Feed (SCoPAFF) for a 
vote, following which the Commission adopts the Regulation. 

Similarly applications for setting or changing Maximum Residue Levels (MRLs) can be submitted by 
an applicant to a Member State which carries out an initial risk assessment and prepares an Evaluation 
Report,  followed  by  an  assessment  of  the  application  and  the  Evaluation  Report  by  EFSA,  which 
adopts a reasoned opinion on the risk to the consumer and where relevant to animals associated with 
the setting, modification or deletion of an MRL. The Commission then prepares a draft Regulation to 
set  (amend  or  remove)  MRLs,  which  is  presented  to  the  Standing  Committee  on  Plants,  Animals, 
Food and Feed (SCoPAFF) for a vote, followed by scrutiny of the draft Regulation by the Council and 
the European Parliament. If neither of them objects, the Commission adopts the Regulation. 

The  Plant  Protection  Products  Regulation  states  that  an  active  substance,  safener  or  synergist  shall 
only  be  approved  if  it  is  not  considered  to  have  endocrine  disrupting  properties  that  may  cause  an 

168 

 
 
adverse  effect  in  humans  or  non-target  organisms,  unless  the  exposure  of  humans/non-target 
organisms to that active substance, safener or synergist, under realistic proposed conditions of use, is 
negligible, or if the substance is necessary to control a serious danger to plant health, which cannot be 
contained  by  other  available  means  including  non-chemical  methods.  If  an  active  substance  is 
considered to have endocrine disrupting properties that may cause an adverse effect in humans, and 
the  derogation  possibilities  are  fulfilled,  it  can  only  be  approved  as  a  candidate  for  substitution  in 
accordance with Article 24 of the Regulation. 

According to Recital (27) of the MRL Regulation, it is necessary that endocrine disrupting properties 
are taken into consideration when setting an MRL.  

The  data  requirements  for  active  substances  and  plant  protection  products  are  described  in 
Regulations  (EU)  No  283/2013  and  (EU)  No  284/2013  respectively.  Regarding  the  toxicological 
assessment,  if  there  is  evidence  that  an  active  substance  may  have  ED  properties,  additional 
information or specific studies are required to elucidate the mode/mechanism of action, and to provide 
sufficient  evidence  for  relevant  adverse  effects.  The  ecotoxicological  assessment  should  consider 
mammalian data. The list of test methods and guidance documents relevant to the implementation of 
these  Regulations  are  presented  in  Commission  Communications  2013/C  95/01  and  2013/C  95/02. 
The  Commission  Communications  are  currently  being  revised  in  order  to  include  methods  that  are 
relevant for the determination of ED properties. 

3  REACH  
Regulation  (EC)  No  1907/2006  concerning  the  Registration,  Evaluation,  Authorisation  and 
Restriction  of  Chemicals  (REACH)  aims  at  improving  the  protection  of  human  health  and  the 
environment  through  the  better  and  earlier  identification  of  the  intrinsic  properties  of  chemical 
substances  while  promoting  alternative  methods  for  the  assessment  of  hazards  of  substancesError! 
Bookmark  not  defined.. This is done by the four processes of REACH, namely the registration, evaluation, 
authorisation and restriction of chemicals. REACH also aims to ensure free circulation of substances 
while enhancing innovation and competitiveness of the EU chemicals industry.  

A  brief  overview  of  REACH  can  be  found  in  the  Staff  Working  document  of  the  last  REACH 
review123.   

In general, all provisions of REACH, including those of registration, evaluation, SVHC-identification, 
authorisation and  restrictions,  apply  to chemical  substances  used  in  other  sectors  for  which  specific 
legislation exist with references to REACH provisions, unless there is a specific exemption mentioned 
in REACH.  

Manufacturers  or  importers  of  chemicals  must  register  their  substances  with  ECHA.  Registration 
requires to provide data on the substance properties. The obligatory information requirements increase 
with  the  tonnage  range.  The  underlying  assumption  for  requesting  less  data  for  lower  tonnage 
substances is that tonnage is a placeholder for exposure, and that due to that the risk from substances 
manufactured  or  placed  on  the  market  in  lower  tonnages  is  also  lower.  Substances  registered  in 
quantities above 10 tonnes per year must undergo a chemical safety assessment (REACH Annex I). 

123SWD(2018) 58, part 1, section 2.1.3.  

169 

 
 
 
                                                      
Provisions of the Substance Evaluation procedure allow ECHA, based on an evaluation by Member 
States, to oblige registrants to provide further data not listed in the information requirements. Any test 
that  is  based  on  a  Test  Guideline  that  is  accepted  by  the  Commission  or  ECHA  can  be  requested, 
including all methods listed in the OECD GD 150 (OECD, 2018). 

ECHA implemented an approach to screen substances in the REACH database using computational 
tools to identify substances that require further regulatory action. The screening includes indications 
of ED properties and allows prioritising substances for further assessments. 

Only a part of the information and tests described in the Conceptual Framework of the OECD GD 150 
for  evaluating  chemicals  for  endocrine  disruption  within  a  tiered  approach,  are  included  in  the 
REACH  Annexes  on  standard  data  requirements.  However,  as  described  above,  further  data  can  be 
requested  from  registrants  via  the  Substance  Evaluation  procedure.  The  European  Commission,  as 
part of its activities outlined in the Commission Communication “Towards a comprehensive European 
Union framework on endocrine disruptors”, has proposed an update of REACH Annexes for inclusion 
of data requirements relevant to endocrine disruption. 

Provisions  under  REACH  for  identifying  substances  with  endocrine  disrupting  properties  are  in 
Article 57 (f) and Article 59. The IPCS/WHO (IPCS, 2002) definition of endocrine disruptors is used 
as  a  basis  for  identifying  substances  of  very  high  concern  (SVHCs)  with  endocrine  disrupting 
properties.  However,  not  all  substances  with  endocrine  disrupting  properties  necessarily  qualify  as 
SVHCs under REACH. It has to be additionally demonstrated that there is scientific evidence that the 
effects of the substance give rise to equivalent level of concern to those mentioned in Article 57 (a) to 
(e)  (substances  meeting  the  criteria  for  classification  as  CMRs  cat.  1A/1B  or  to  persistent, 
bioaccumulative and toxic (PBT) substances,  or to very persistent and very bioaccumulative (vPvB) 
substances).  As  for  other  regulations,  REACH  distinguishes  when  identifying  endocrine  disruptors 
between  substances  having  effects  on  human  health  and  substances  having  effects  on  the 
environment. 

To be identified as a SVHC, it is not required that a substance is registered under REACH or that it is 
manufactured  in  the  EU,  imported  or  used.  The  identification  of  SVHCs  with  endocrine  disrupting 
properties  can  apply  in  principle  to  all  chemical  substances,  irrespective  of  whether  sectorial 
legislation is regulating the use of a chemical. Inter alia, REACH can identify substances as SVHCs 
when  they  are  used  e.g.  in  cosmetic  products,  toys,  food  contact  materials,  or  as  co-formulants  in 
biocidal and plant protection products. 

Member States or ECHA (on behalf of the Commission) assess whether a substance exerts potentially 
endocrine-related  adverse  effects,  whether  scientific  evidence  allows  establishing  an  endocrine 
activity and whether a scientifically plausible link between endocrine activity and adverse effects can 
be shown. The assessment is documented in a dossier following the requirements of REACH Annex 
XV124. The Member State Committee (MSC) at ECHA decides by unanimity whether a substance is 
identified as an SVHC with endocrine disrupting properties. If there is not unanimity within the MSC, 
the responsible comitology Committee (REACH Committee) votes on a draft decision prepared by the 
Commission. 

124Annex XV: Dossiers – general principles of preparing dossiers to propose and justify the identification of 
CMRs, PBTs, vPvBs or a substance of equivalent concern (such as EDs) as well as restrictions on the 
manufacture or placing on the market or use of a substance within the community. 

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The use of substances identified as SVHCs with endocrine disrupting properties can be subjected to 
the  REACH  authorisation  procedure  as  described  in  REACH  Title  VII  (authorisation).  Substances 
regulated  via  some  of  the  sectorial  pieces  of  legislation  are  partially  or  totally  excluded  from  the 
authorisation  requirement  under  REACH.  This  is  based  on  the  rationale  that  sectorial  legislation  is 
providing provisions for risk assessment and risk management of the use of substances in the sectorial 
areas. Several pieces of legislation already cover the assessment of risks to human health, but not risks 
to  the  environment.  In  these  cases,  REACH  authorisation  applies  to  substances  that  have  been 
identified  as  SVHCs with  endocrine disrupting  properties having  effect on the  environment.  This  is 
the case for substances used in a) cosmetic products, b) medical devices and c) food contact materials. 
REACH  does  not  exclude  substances  used  in  toys  from  the  authorisation  requirement,  for  either 
SVHC with effects to the environment or to human health. 

The identification of a substance as SVHC with endocrine disrupting properties is not a precondition 
for  taking  regulatory  risk  management  measures  under  REACH  other  than  authorisation.  The 
restriction  process  addresses  unacceptable  risks  to  human  health  or  the  environment  posed  by  any 
substance  that  requires  Union-wide  action.  The  manufacture,  use  or  placing  on  the  market  of  those 
substances on their own, in mixtures or in articles may be restricted for some uses or even completely 
banned, if necessary. Several substances which are endocrine disruptors have been restricted (Error! 
Reference source not found.). The standard restriction procedure can be launched on the initiative of 
a Member State or by ECHA (acting on a request from the Commission). It requires the preparation of 
an  Annex  XV  dossier,  which  should  include  information  on  hazard  and  risk,  information  on 
alternative  substances,  justification  for  restrictions,  and  socio-economic  information.  Relevant 
information is further gathered via a public consultation and by consulting the Forum for Exchange of 
Information on Enforcement (Forum). The scientific committees at ECHA (RAC and SEAC) assess 
the  information  in  the  dossier  and  gathered  via  the  consultations  and  provide  opinions  to  the 
Commission,  which  drafts  then  a  decision  and  submits  it  to  the  responsible  Comitology  committee 
(REACH Committee). REACH restrictions apply in general to uses of substances or to the placing on 
the market of substances or articles in other sectors unless exempted by specific REACH provisions. 
This includes inter alia substances used in cosmetic products (only with regard to addressing risks to 
the environment), toys, food contact material, medical devices, detergent substances used in biocidal 
products (active substances, co-formulants), and substances used in plant protection products (active 
substances, co-formulants) etc. 

4  Classification, Labelling and Packaging (CLP) 
The Regulation (EC) N° 1272/2008 on the Classification, Labelling and Packaging of substances and 
mixtures (CLP Regulation) determines whether a substance or mixture displays properties that lead to 
a hazard classification and ensures that such hazards are communicated through consistent labelling 
along the supply chain including workers and consumers. Manufacturers, importers and downstream 
users must evaluate (Article 5) and classify (Article 13) substances according to classification criteria 
laid out in Annex I.  

In  the  CLP  Regulation,  the  EU  implements  almost  completely  the  United  Nations  Globally 
Harmonised System (GHS) for classification and labelling of chemicals. Classification categories in 
Annex  I  include  inter  alia  germ  cell  mutagenicity  (section  3.5),  carcinogenicity  (section  3.6)  and 
reproductive  toxicity  (section  3.7)  and  specific  target  organ  toxicity  (STOT),  single  and  repeated 
exposure  (sections  3.8  and  3.9).  For  ecotoxicity,  a  generic  hazard  category  for  the  aquatic 
environment  is  listed  (short  and  long  term).  Classification  takes  into  account  the  total  weight  of 

171 

 
 
evidence, (Article 5 and section 1.1.1 of Annex I). This means that all available information that bears 
on the determination is considered together (Article 5).  

There  are  no  classification  criteria  for  EDs,  however  effects  on  endocrine  organs  are  explicitly 
mentioned as relevant to reproductive toxicity: relevant information includes epidemiological studies 
and  case  reports  in  humans  and  specific  reproduction  studies  along  with  sub-chronic,  chronic  and 
special  study  results  in  animals  that  provide  relevant  information  regarding  toxicity  to  reproductive 
and related endocrine organs (CLP, Annex I, 3.7.2.3.1) 

Generic  and  specific  concentration  limits  are  established  (Article  10)  for  the  classification  of 
substances and mixtures. The Regulation applies, as a general principle, to all substances and mixtures 
supplied  in  the  EU  but  not  to  chemicals  that  are  in  the  finished  state  intended  for  the  final  user: 
medicines, medical devices, cosmetic products, veterinary medicines, food and feeding stuff such as 
food additives, food flavouring and feeding stuffs used in animal nutrition (Article 1.2). CLP acts as a 
horizontal  reference  point  for  a  large  number  of  the  EU  chemicals  and  chemical-related  legislation 
designed to ensure consistency in chemical hazard identification and classification.    

The  REACH  Regulation,  the  Regulation  on  Biocidal  Products  (BPR),  the  Regulation  on  Plant 
Protection Products (PPPR) and the CLP Regulation are closely interlinked. The obligation to classify 
is based on the CLP Regulation (Article 4). The provisions of the CLP Regulation apply in full to any 
substance or mixture whose marketing and use are controlled by the BPR or the PPPR.  

Many other pieces of legislation refer to CLP hazard classes and categories in their provisions, often 
with  direct  implications  for  risk  management.  Examples  of  legislation  including  such  references 
include  REACH,  cosmetic  products,  food  contact  materials,  toys,  medical  devices  and  in  vitro 
diagnostic  medical  devices,  occupational  safety  and  health  (OSH)  legislation  (including  chemical 
agents at work, carcinogens and mutagens at work, young people at work, pregnant and breastfeeding 
women at work directives), ecolabel, industrial emissions directive, detergents, hazardous waste.  

5  POPs Regulation 
The  Persistent  Organic  Pollutants  (POPs)  Regulation  (EU)  2019/1021  implements  two  worldwide 
agreements,  the  Stockholm  Convention125  and  the  Aarhus  Protocol126  to  the  Convention  on  Long-
Range  Transboundary  Air  Pollution,  without  including  specific  provisions  for  ED  identification.  Its 
aim  is  to  protect  human  health  and  the  environment  from  the  risk  posed by  organic  substances  that 
persist in the environment, accumulate in living organisms. 

Under the Stockholm Convention, POPs are defined by criteria of persistence, bioaccumulation, long-
range transport and adverse effects (paragraph 1 of Annex D to the Convention). Adverse effects are 
demonstrated by toxicity or ecotoxicity  data indicating  the potential for damage to human  health or 
the environment. If a substance fulfils the Annex D criteria, a risk profile in accordance with Annex E 
to the Convention is prepared. If it is concluded on the basis of the risk profile that a substance leads 
to significant adverse human health and environmental effects such that global action is warranted, a 
risk management evaluation is prepared, which considers socio-economic aspects in accordance with 
Annex  F  to  the  Convention.  On  the  basis  of  the  risk  management  evaluation,  a  recommendation  is 
made  to  include  the  substance  in  Annex  A  (ban  with  or  without  specific  exemption),  Annex  B 
(restriction  with  or  without  acceptable  purpose  or  specific  exemption)  or  Annex  C  (in  case  of 

125http://www.pops.int 
126https://www.unece.org/env/lrtap/pops_h1.html 

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unintentional  production)  to  the  Convention.  Following  the  inclusion  of  a  substance  in  the 
Convention, the substance is listed in the POP regulation. 

The Regulation  defines requirements for the reporting on environmental release inventories (Article 
6)  environmental  monitoring  (Article  10)  and  production  volumes  (Article  13)  of  POPs.  Release 
should  be  minimised  or  eliminated  from  all  sources  (Article  6)  including  waste  (Article  7).  Waste 
containing  or  contaminated  with  POPs  should  be  handled  to  ensure  no  release  or  recirculation  in 
material flows.  

When a substance is prohibited or restricted in the POPs Regulation, the Commission withdraws the 
authorisation for that use under REACH. When a substance restricted under REACH is subsequently 
listed  under  the  Stockholm  Convention,  the  practice  is  to  implement  the  listing  in  the  Stockholm 
Convention  by  amending  the  appropriate  Annex(es)  to  the  POPs  regulation  and  to  remove  the 
restriction from REACH (examples of this are decaBDE, pentaBDE and PFOAs).  

6  Toys 
The  Toy  Safety  Directive  (2009/48/EC)  aims  to  ensure  that  “toys  including  the  chemicals  they 
contain,  shall  not  jeopardise  the  safety  or  health  of  users  or  third  parties  when  they  are  used  as 
intended or in a foreseeable way, bearing in mind the behaviour of children”. Regarding chemicals 
the  directive  sets  a  number  of  limitations,  such  as  for  metals  or  allergenic  fragrances.  It  is  closely 
interconnected with the CLP regulation, such as concerning the prohibition of CMR substances, and 
the REACH regulation, such as concerning the restriction of phthalates. In general, all provisions of 
REACH apply to chemical substances used in toys. 

The directive does not have specific provisions for EDs. However, it allows to establish specific limit 
values  for  any  chemical  (including  EDs)  in  toys  for  children  under  36  months  of  age  and  for  toys 
intended  to  be  placed  in  the  mouth  (Appendix  C).  So  far,  this  approach  has  been  used  for  CMR 
substances such as bisphenol A but also for strongly sensitising substances. 

CMR substances cat. 1A, 1B or 2 are prohibited in principle (Annex II, Part III, point 3). However, by 
derogation CMRs may be used in toys up to the relevant limits in the CLP regulation. CMRs may also 
be permitted by the Commission if certain criteria are fulfilled (Annex II, Part III, point 4 for cat. 1 
CMRs, Annex II, Part III, point 5 for cat. 2 CMRs). The criteria include a safety evaluation with an 
opinion of the relevant Scientific Committee that the use of the CMR in toys is safe. 

7  Food legislation 

  Food Contact Materials 

7.1
Alongside EU food law (EC) No 178/2002, Regulation (EC) No 1935/2004 aims to protect consumers 
from  exposure  to  substances  migrating  from  food  contact  materials  and  articles  (FCM)  into  food. 
FCM are either intended to be brought into contact with food, are already in contact with food, or can 
reasonably be brought into contact with food or transfer their constituents to the food under normal or 
foreseeable use and includes direct or indirect contact. Examples include containers for transporting 
food, machinery to process, store food, packaging materials as well as kitchenware and tableware.  

The objectives of the FCM Regulation are to ensure the effective functioning of the internal market in 
relation  to  the  placing  on  the  market  in  the  Union  of  materials  and  articles  intended  to  come  into 
contact  directly  or  indirectly  with  food,  whilst  providing  the  basis  for  securing  a  high  level  of 
protection of human health and the interests of consumers. Specific rules have been introduced at EU 

173 

 
 
level  mainly  on  the  composition  of  plastic  FCMs,  including  an  authorised  list  of  substances  and 
associated restrictions. However, rules also exist on active and intelligent packaging (AIM), ceramic-
ware,  regenerated  cellulose  film,  some  specific  substances  and  processes  to  recycle  plastic,  all 
focussed on chemical safety. 

The  use  of  chemicals  in  FCMs  in  relation  to  protection  of  the  environment  is  regulated  under 
REACH.  As  FCMs  are  already  regulated  in  relation  to  human  health  by  the  Regulation  (EC)  No 
1935/2004,  FCMs  are  exempted  from  some  of  the  requirements  in  REACH.  This  means  that  the 
REACH authorisation procedure does not apply to FCMs, unless the chemical enters the authorisation 
process  under  REACH  due  to  environmental  health  concerns  (Article  56(5)(b)  of  REACH)  and  the 
chemical safety report is not required to include an evaluation of human health risks (Article 14(5)(a) 
of REACH). However, for certain substances, the restrictions laid down in Annex XVII to REACH 
apply  equally  to  those  found  in  FCMs,  such  as  phthalates  in  articles  used  for  feeding  children, 
polycyclic  aromatic  hydrocarbons  (8  PAHs)  in  all  articles  where  oral  exposure  occurs,  and 
perfluorooctanoic acid (PFOA). 

The FCM Regulation does not contain specific provisions for EDs. However, substances for which an 
authorisation is required, such as  monomers and additives in plastic FCM, require an  evaluation  by 
the  European  Food  Safety  Authority  (EFSA).  EFSA  requires  specific  studies  depending  on  the 
migration level to food based on a tiered-approach. For example, in the case of plastic FCM, where 
migration is relatively high (i.e. migration 5 – 60mg/kg food) studies investigating reproductive and 
developmental toxicity are required (EFSA Panel on Food Contact Materials et al., 2008). In its work, 
EFSA  evaluates  hazardous  properties  and  risks  of  substances  by  examining  data  on  migration  and 
potential  exposure.  The  resulting  risk  management  action  is  therefore  based  on  the  risk  from  the 
substance,  rather  than  purely  intrinsic  hazardous  properties.  Legal  reference  is  only  made  to  CMR 
substances,  which  require  assessment  even  if  they  are  used  behind  a  functional  barrier  (to  avoid 
migration) according to specific EU rules on plastics and AIM. 

In  addition,  EFSA  may  evaluate  or  re-evaluate  substances  considering  additional  information  that 
becomes available since the initial assessment. Such is the case for bisphenol A (BPA) where EFSA 
continues  to  date,  to  assess  scientific  information  on  the  endocrine  disrupting  properties  of  BPA. 
However, the 2015 EFSA opinion on BPA (EFSA Panel on Food Contact Materials et al., 2015) has 
already  resulted  in  increased  risk  management  action  by  the  Commission127,  including  further 
restrictions  based  on  the  precautionary  principle.  More  recently,  EFSA  has  assessed  the  risk  from 
phthalates from the diet (EFSA Panel on Food Contact Materials et al., 2019), taking into account new 
information  available  on  the  toxicity  to  reproduction  of  these  substances  assessed  by  ECHA  under 
REACH  and  for  which  the  Commission  is  taking  follow-up  action  concerning  their  use  in  plastic 
FCM (see also Annex 1, DEHP case study). 

EFSA  has  also  recently  published  a  scientific  opinion  which  describes  recent  developments  in  the 
safety assessment of chemicals in food and explores their potential impact on its evaluations of FCM 
(EFSA Panel on Food Contact Materials et al., 2016). The opinion indicates that the use of the most 
recent updated versions of test guidelines and new methodologies which includes potential endocrine 

127Commission Regulation (EU) 2018/213 - on the use of bisphenol A in varnishes and coatings intended to 
come into contact with food and amending Regulation (EU) No 10/2011 as regards the use of that substance in 
plastic food contact materials 

174 

 
 
 
                                                      
disruptors  (as  from  OECD  GD150,  2018),  as  well  as  immunotoxicity  and  neurotoxicity  effects 
identification may be needed depending first on the initial testing strategy. 

Currently, the European Commission is carrying out an evaluation to assess to what extent the current 
EU  legislative  framework  for  FCMs  is  fit  for  purpose  and  delivers  as  expected.  The  evaluation  has 
been  examining,  inter  alia,  the  coherence  with  other  legislation,  such  as  REACH.  Whilst  the 
evaluation is still ongoing, the Commission is also in the process of preparing an impact assessment 
on  new  FCM  rules,  taking  into  account  the  information  already  collected  from  the  FCM  evaluation 
and  other  initiatives,  such  as  this  ED  Fitness  Check,  whilst  complementing  the  already  established 
information. 

  Contaminants in feed and food 

7.2
Under  the  European  framework  legislation,  Council  Regulation  (EEC)  No  315/93  lay  down 
procedures  for  contaminants  in  food  and  Directive  2002/32/EC  provides  for  the  establishment  of 
regulatory  levels  on  undesirable  substances  (contaminants)  in  feed.  Contaminants  in  food  are  any 
substance not intentionally added to food which is present in such food as a result of the production 
(including  operations  carried  out  in  crop  husbandry,  and  animal  husbandry),  manufacture, 
processing,  preparation,  treatment,  packing,  packaging,  transport  or  holding  of  such  food  or  as  a 
result of environmental contamination. In feed, undesirable substances (contaminants) are defined as 
any  substance  or  product  which  is  present  in  and/or  on  the  product  intended  for  animal  feed  and 
which  presents  a  potential  danger  to  animal  or  human  health  or  to  the  environment  or  could 
adversely affect livestock production. With regard to residue levels of pesticides in food or feed, those 
are covered by Regulation (EC) No 396/2005 on maximum residue levels of pesticides in or on food 
and feed of plant  and animal origin (see paragraph 3.2). With regard to residue levels of veterinary 
medicinal products administered to food-producing animals and present in food, those are covered by 
Regulation (EC) No 470/2009. 

Council  Regulation  (EEC)  No  315/93  provides  the  basis  for  establishing  maximum  levels  or 
maximum  tolerances  for  certain  contaminants  but  does  not  identify  specific  substances  for  which 
maximum levels are to be established. Maximum levels are set in Commission Regulation (EC) No 
1881/2006 for e.g. nitrates, mycotoxins, metals, dioxins and PCBs, polycyclic aromatic hydrocarbons.   

As  such,  Commission  Regulation  (EC)  No  1881/2006  does  not  contain  specific  provisions  for  the 
identification,  risk  assessment  and  risk  management  of  endocrine  disruptors.  However,  potential 
effects of endocrine disruptors are also covered by Annex XVII to REACH, on restriction of use, and 
several  substances  listed  in  that  Annex  fall  within  the  scope  of  the  contaminants  legislation  when 
present  in  food.  Restriction  of  use  of  these  substances  can  effectively  result  in  preventing  or 
minimising their presence in food.   

Indirect protection to potential endocrine disrupting effects related to the presence of contaminants in 
food  is  also  ensured  by  Directive  2002/32/EC  on  undesirable  substances  in  animal  feed  which,  in 
Article 3 states that: products intended for animal feed may enter for use in the Community from third 
countries, be put into circulation and/or used in the Community only if they are sound, genuine and of 
merchantable  quality  and  therefore  when  correctly  used  do  not  represent  any  danger  to  human 
health, animal health or to the environment or could adversely affect livestock production. Hence, in 
case the presence of a potential endocrine disrupting chemical in food of animal origin is the result of 
the transfer from feed into food of animal origin,  the presence of this potential endocrine disrupting 
chemical in food has to be minimised by regulating this chemical in feed. 

175 

 
 
 
 
 
  Food additives 

7.3
Regulation (EC) No 1333/2008 covers food additives and Regulation (EC) No 1331/2008 establishes 
a common authorisation procedure for food additives, food enzymes and food flavourings.  

The  most  recent  implementation  (Commission  Regulation  (EU)  No  234/2011)  describes  a  common 
authorisation procedure for food additives, food enzymes and food flavourings including data required 
for  safety  assessment.  The  regulations  do  not  specifically  address  endocrine  disrupting  properties 
however,  some  of  the  data  required  (by  Article  6  of  Regulation  (EU)  No  234/2011),  such  as  sub-
chronic toxicity; chronic toxicity/carcinogenicity; reproductive and developmental toxicity are able to 
provide  information  on  endocrine  properties,  particularly  where  additional  endocrine-related 
parameters have been  recently included  (e.g. thyroid hormone levels in subchronic toxicity  tests) to 
place  more  emphasis  on  endocrine-related  endpoints.  The  EFSA  Guidance  for  submission  of  food 
additive  evaluations  (EFSA  Panel  on  Food  Additives  and  Nutrient  Sources  added  to  Food,  2012) 
describes a tiered-approach for the safety assessment requiring subchronic toxicity testing within Tier 
1  that  also  includes  additional  parameters  on  endocrine-related  endpoints,  (e.g.  determination  of 
thyroid  hormones,  gross  necropsy  and  histopathology  of  tissues  that  are  indicators  of  endocrine-
related  effects)  allowing  for  the  identification  of  effects  that  may  warrant  further  in-depth 
investigation.  In  addition,  Commission  Regulation  (EU)  No  234/2011  lays  down  specific  data 
required for risk assessment and data required for risk management of food additives (Articles 6 and 
7)  as  well  as  food  enzymes  (Article  8  and  9)  and  flavourings  (Articles  10-11).  For  food  additives, 
these  contribute  to  establishing  normal  and  maximum  use  levels  of  food  categories  included  in  the 
Union  list  of  approved  food  additives  (Regulation  (EC)  No  1333/2008  Annex  II)  with  related 
management  measures  and  provide  coverage  of  potential  endocrine  disruptors  by  using  the  most 
recent updated versions of the Test Guidelines.  

8  Cosmetic Products 
Regulation  (EC)  No  1223/2009  on  cosmetic  products  (CPR  or  “Cosmetics  Regulation”)  aims  to 
ensure  a  high  level  of  protection  of  human  health  by  providing  a  framework  for  assessing  and 
managing  cosmetic  ingredients.  Its  scope  is  limited  to  the  functioning  of  the  internal  market  and  a 
high  level  of  protection  of  human  health,  whereas  environmental  concerns,  including  the 
identification  and  regulation  of  environmental  EDs,  are  addressed  under  the  REACH  regulation. 
Within  the  human  health  domain,  the  regulation  establishes  its  own  framework  for  risk  assessment 
and  risk  management.  However,  substances  used  in  the  cosmetics  sector  over  1  tonne  per  year  are 
subject  to  the  REACH  registration,  which  includes  data  generation  as  laid  down  in  the  standard 
information requirements of (Chapter 3.2 of REACH). REACH, however, exempts substances used in 
cosmetics specifically from the chemical safety report/chemical safety assessment for human health. 
Instead, the CPR requires evaluation of the finished cosmetic product through the Cosmetic Product 
Safety Report. 

Annex  II  to  the  CPR  lists  substances  prohibited  in  cosmetics  products.  Annex  III  lists  restricted 
substances that shall be used in accordance with the restrictions laid down therein. Certain categories 
of ingredients, namely colorants, preservatives and UV-filters, can only be used in cosmetic products 
if  they  have  been  authorised  through  their  inclusion  in  the  so-called  “positive  lists”  of  the  CPR 
(Annexes IV, V and VI).  

For all cosmetic products made available on the EU market, the operator designated as the responsible 
person  shall  ensure  that  the  cosmetic  product  undergoes  a  safety  assessment  and  that  a  cosmetic 
product safety report is set up. In case of identified potential risk to human health or for adaptation to 

176 

 
 
technical  and  scientific  progress  the  Commission  can  prohibit  or  restrict  ingredients  from  use  in 
cosmetic products by amending the relevant Annexes to the CPR. Amendments to the Annexes of the 
CPR  (inclusion  of  new  substances  or  revision  of  existing  entries)  are  preceded  by  a  scientific  risk 
assessment  conducted  by  the  Scientific  Committee  on  Consumer  Safety  (SCCS).  According  to  the 
SCCS  Notes  of  Guidance  (SCCS,  2018),  in  the  risk  assessment  procedure  for  substances  used  as 
cosmetic ingredients, the SCCS considers, among other factors, the exposure assessment for specific 
vulnerable groups, such as children and pregnant women.  

Article 15 of the CPR governs the use in cosmetic products of substances which have been classified 
as  carcinogenic,  mutagenic  or  toxic  for  the  reproduction  (CMR)  under  the  CLP  regulation.  CMR 
substances of category 1A or 1B and of category 2 under Part 3 of Annex VI to Regulation (EC) No 
1272/2008 shall be prohibited from use in cosmetic products unless a derogation is granted. Article 
15(1)  governs  the  derogations  that  might  apply  to  CMR  substance  classified  in  category  2.  This 
requires  that  the  substance  is  evaluated  by  the  SCCS  and  found  safe  for  use  in  cosmetic  products, 
while Article 15(2) governs the derogations that might apply to substance classified as CMR 1A  or 
1B.  

The CPR does not have any specific provisions for EDs. For substances that have been identified or 
have  potential  endocrine  disrupting  properties,  but  are  not  classified  as  CMRs,  the  assessment  of 
potential risk to human health is governed by the general provisions of Article 31. Article 31 provides 
that  where  there  is  a  potential  risk  to  human  health,  arising  from  the  use  of  substances  in  cosmetic 
products, which needs to be addressed at EU level, the Commission may, after consulting the SCCS, 
amend  Annexes  II  to  VI  accordingly.  The  ability  of  the  regulation  to  identify  and  assess  potential 
endocrine disrupting substances depends on the toxicological data related to potential ED  modalities 
available to the SCCS. The CPR does not set specific toxicity test requirements. However, there are 
explicit  guidelines  included  in  the  SCCS  Notes  of  Guidance  that  follow  the  recommendations  of 
WHO and OECD on this issue.  

Article  18  prohibits  animal  testing  of  finished  cosmetic  products  and  cosmetic  ingredients  (“testing 
ban”)  as  well  as  the  placing  on  the  EU  market  of  cosmetic  products  and  their  ingredients  tested  on 
animals  in  order  to  meet  the  requirements  of  the  CPR.  Since  its  enforcement,  only  in  silico  and  in 
vitro methods can be used to evaluate safety. However, in vivo studies may still be used if performed 
before the animal testing ban or if they become available through the requirement of other regulatory 
processes such as PPPs, biocides and REACH. 

Cosmetic  ingredients  could  be  assessed  for  endocrine  properties  in  a  stepwise  approach  using  non-
animal methods (in silico models, read across, in vitro assays, other mechanistic techniques such as 
'omics') and/or data generated outside the cosmetics sector. Regarding reproductive toxicity three non-
animal  methods  have  been  developed  and  validated  by  ECVAM  for  embryotoxicity  screening 
purposes.  Overall,  as  recognised  in  the  Memorandum  SCCS/1544/14  and  in  the  SCCS  Notes  of 
Guidance, the complex endpoint of reproductive toxicity is not covered by the above systems and no 
alternative  methods  are  currently  available  covering  the  whole  area.  In  practice,  many  recent 
evaluations and decisions have relied on historical in vivo data generated before the animal testing ban 
in combination with evidence emerging from non-animal methods.  

As  per  Article  15(4),  the  Commission  has  consulted  the  SCCS  when  reviewing  the  regulation 
regarding  substances  with  endocrine-disrupting  properties128.  The  review  concluded  that  “the 

128COM(2018) 739 

177 

 
 
                                                      
to 

in  cosmetics”. In 

experience  collected  since  the  entry  into  application  of  the  Cosmetics  Regulation  has  not  revealed 
elements  which  would  justify  deviating  from  the  regime  designed  by  the  legislator  to  address  the 
the  same 
safety  concerns  related 
the  use  of  endocrine  disruptors 
Communication, the Commission committed to establish a priority list of potential EDs not already 
covered by bans or restrictions in the CPR for their subsequent safety assessment. A priority list of 28 
potential EDs in cosmetic products was consolidated in early 2019 based on input provided through a 
stakeholder consultation129. In 2019 the Commission organised a public call for data on 14 of the 28 
substances  (to  be  treated  with  higher  priority)  to  enable  the  preparation  of  the  safety  assessment  of 
these  substances.  In  February  2020  the  Commission  mandated  the  SCCS  to  carry  out  the  risk 
assessments  with  an  updated  evidence  base  for  five  substances,  including  one  hair  dye  (resorcinol), 
one preservative (propylparaben) and three UV-filters (octocrylene, homosalate and benzophenone-3). 
The mandate set a nine-month deadline for the SCCS to adopt the preliminary opinions. Concerning 
the  remaining  nine  substances  with  suspected  endocrine  disrupting  properties,  the  Commission  has 
requested  additional  data  to  proceed  with  the  risk  assessment.  Provided  that  new  scientific  data  are 
submitted, the Commission will proceed in mandating the SCCS in the first half of 2021.   

9  Medical devices and in vitro diagnostics 
The  Medical  Devices  Regulation  (MDR)  (EU)  2017/745  and  the  Regulation  (EU)  2017/746  on  In 
Vitro  Diagnostics  (IVDR)  adopted  in  May  2017  will  apply  from  May  2021130  and  May  2022, 
respectively. 

Medical devices are critical for health and safety of patients and are often lifesaving. Therefore, the 
special  and  fundamental  feature  of  the  regulatory  framework  on  medical  devices  is  the  principle  of 
benefit-risk ratio, i.e. the benefit of the device must outweigh the risks for it to be compliant.  

Both  Regulations  have  specific  provisions  (Annex  I)  on  substances  with  endocrine  disrupting 
properties  with  effects  on  human  health.  With  reference  to  the  MDR  and  only  for  certain  types  of 
devices  the  manufacturer  is  required  to  perform  a  thorough  justification  for  the  presence  of  such 
substances at a concentration above 0.1% w/w. This justified exemption procedure is not included in 
the  IVDR.  Such  justification  shall  be  based,  among  others,  on  an  analysis  of  possible  alternative 
substances.  For  identification  of  substances  with  endocrine  disrupting  properties  for  human  health, 
reference  is  made  to  REACH,  and  only  for  the  MDR,  to  the  Biocidal  Products  Regulations,  which 
have processes in place to update the list of these substances. 

To satisfy the requirements of MDR and IVDR Regulations, the manufacturer must demonstrate that 
the benefit of the device placed on the market offsets the risks from use of substances with endocrine 
disrupting  properties  to  human  health.  Regarding  possible  benefit,  SCHEER  was  mandated  by  the 
Commission to draft Guidelines for the benefit/risk assessment on the presence of phthalates having 
endocrine disrupting properties in certain medical devices (SCHEER, 2019). 

10 Human and veterinary medicines 

Human and veterinary medicines are regulated respectively by Directive 2001/83/EC and by Directive 
2001/82/EC, to be replaced as of January 2022 by Regulation 2019/6. The regulatory framework for 
human  and  veterinary  medicines  follows  a  different  logic  than  for  other  chemicals,  with  the  main 

129https://ec.europa.eu/growth/sectors/cosmetics/products/endocrine_en/ 
130http://data.europa.eu/eli/reg/2020/561/oj 

178 

 
 
                                                      
emphasis on the therapeutic benefit for the target group evaluated in the context of possible adverse 
side  effects  and  risks  to  target  organisms  (patients  and  treated  animals).  The  rationale  for  including 
this  policy  area  in  this  FC  is  primarily  related  to  those  provisions  aiming  at  protecting  non-target 
organisms  in  the  environment131.  The  forthcoming  Commission  EU  Pharmaceutical  strategy  will 
further consider the environmental aspects of medicinal products, including effects of EDs as part of 
the  implementation  of  the  Commission  Communication  on  the  EU  strategic  approach  of 
pharmaceuticals in the environment (COM(2019) 128).  

Whereas  there  is  no  formal  requirement  for  ED  identification  for  pharmaceuticals  and  veterinary 
medicines, in both cases concerns related to the environmental impact of endocrine properties can be 
addressed through environmental risk assessment. It can be expected that information relevant to the 
assessment  of  endocrine  disrupting  properties  in  these  sectors  comes  from  data  generated  in  the 
context of safety to target organisms. It should always be kept in mind that the intended purpose and 
mechanism of action of the medicine concerned may target the hormonal system of the body. These 
medicines may be life-saving and used in treatment of severe chronic diseases 

Directive  2001/83/EC  requires  that  the  application  for  marketing  authorisation  of  a  medicine  for 
human use should include an environmental risk assessment to evaluate the risks due to the use and/or 
disposal  of  the  medicinal  product  on  the  environment.  Reproductive  and  developmental  toxicity  is 
investigated as part of the toxicological assessment. In addition, the environmental risk assessment of 
medicinal products for human use, requires a tailored evaluation of a potential endocrine effect on the 
environment  if  a  direct  mechanism  of  action  is  affecting  reproduction.  This  tailored  assessment  is 
necessary  in  order  to  ensure  that  the  most  sensitive  and  appropriate  tests  with  specific  groups  of 
organisms are used in the assessment and a phase II ERA always needs to be performed irrespective 
of  the  predicted  exposure  in  surface  water.  The  EMA  guideline  on  the  ERA  is  currently  under 
revision.  In  the  draft  revision132  published  for  public  consultation,  the  identification  of  endocrine 
active substances has been broadened compared to the current guideline in order to include all active 
substances which may affect development or reproduction through effects linked to steroid hormone 
pharmacology,  and  does  not  address  potential  thyroid  disruptors.  The  rationale  for  this  is  that 
compounds acting on steroid receptors are known to have pharmacological activities at concentrations 
below  the  current  action  limits  and  some  have  shown  to  have  effects  on  aquatic  organisms  at  the 
population  level  at  very  low  concentrations. This  level  of  evidence  is  currently  not  available  for 
compounds  acting  on  the  thyroid  system.   Nevertheless,  if  for  a  substance  acting  on  the  thyroid 
system  the  action  limit  is  exceeded,  it  would  be  expected  that  a  tailored  risk  assessment  would  be 
performed as recommended in the draft guidance document. This draft guidance also includes a list of 
recommended  tests  to  address  (anti)estrogenic,  anti(androgenic)  and  thyroid  effects.    These  aspects 
will be further considered under the forthcoming EU Pharmaceutical Strategy. 

Regarding  medicines  for  veterinary  use,  the  straightforward  application  of  the  environmental  risk 
assessment  (guidelines  and  tests)  (EMA,  2016)  does  not  address  endpoints  relevant  to  endocrine 
disruption,  and  hence  recommended  tests  (i.e.,  OECD  TGs)  are  not  suitable  for  identifying  if  the 
substance  is  a  potential  ED.  However,  endocrine  disrupting  effects  can  be  addressed  within  an 
environmental risk assessment when there is an underlying concern that the substance is a potential 

131The 2019 Commission Fitness check (COM(2019) 264 final) of the chemicals legislation excluded from its 
scope the pharmaceuticals, veterinary and food additives legislation "because their hazard and risk assessment 
is based on different considerations (i.e. an assessment of the risk trade-offs between the health benefits of the 
medical product versus potential undesired side-effects).  
132EMEA/CHMP/SWP/4447/00 Rev. 1, draft version published in 2018 

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ED,  based  on  changes  indicative  of  endocrine  dysfunction  reported  in  the  repeated  dose  toxicity 
study, or other evidence available (e.g., QSAR data, presence of structural alert, literature studies). In 
this  case,  the  applicant  can  be  requested  to  conduct  special  studies  as  part  of  the  authorisation 
application, even when environmental exposure is predicted to be very low. 

The  outcome  of  the  environmental  risk  assessment  does  not  influence  the  approval  of  human 
medicines but is considered for veterinary medicines. In this case, evidence of an environmental risk, 
which  cannot  be  controlled  with  risk  management/mitigation  measures,  can  prevent  the  granting  of 
the authorisation, if the risk is considered to outweigh the benefits of the product.  

In  addition,  Regulation  2019/6  on  medicinal  products  for  veterinary  use  highlights  the  need  to 
examine  a  substance  of  concern  in  the  broader  context  of  the  EU  environmental  legislation,  e.g.  to 
identify during the authorisation procedure if such substances should be included in the ‘Watch list’ of 
Directive  2000/60/EC,  in  order  to  gather  monitoring  data  on  them.  If  an  environmental  quality 
standard  is  requested  and  it  is  necessary  to  identify  measures  to  reduce  its  emissions  to  the 
environment, such as measure to reduce emissions from manufacturing by following Best Available 
Techniques (BAT), a substance will be included in the Priority Substances list. 

11 Occupational Safety and Health legislation (OSH) 
The EU OSH legislation comprises the Framework Directive 89/391/EEC, which lays down the main 
principles  of  prevention  and  protection  of  occupational  risks,  and  amongst  others  includes  the 
following individual and related Directives: the Chemical Agents at Work Directive, the Carcinogens 
and  Mutagens  at  Work  Directive,  the  Pregnant  Workers  Directive  and  the  Young  People  at  Work 
Directive.  

The Chemical Agents at Work Directive (98/24/EC) covers all chemical agents that present a risk 
to the safety and health of workers, which includes chemicals toxic to reproductive health as well as 
substances with endocrine disrupting properties if there is a risk for workers. 

A  hazardous  chemical  agent  according  to  Article  2  of  this  Directive  is  any  chemical  that  meets  the 
CLP  classification  criteria  whether  or  not  the  chemical  is  classified  under  the  CLP  Regulation.  If  a 
chemical  does  not  meet  the  criteria  for  classification  as  hazardous  according  to  CLP,  it  may  still 
present  at  risk  to  the  safety  and  health  of  workers,  due  to  its  physicochemical,  chemical  or 
toxicological properties and the way it is used or is present in the workplace including any chemical 
agent that is assigned an occupational exposure limit value under Article 3 of the Directive.  

The  employer  assesses  any  risk  to  the  safety  and  health  of  workers  arising  from  the  presence  of 
hazardous chemical agents at the workplace and takes preventive and protective measures to protect 
workers. The Directive provides a hierarchy of risk management measures to protect workers from the 
risks. 

The Carcinogens and Mutagens at Work Directive (2004/37/EC) aims to protect workers against 
risks to their health and safety, including the prevention of such risks, arising or likely to arise from 
exposure  to  carcinogens  or  mutagens  at  work.  As  such,  substances  toxic  for  reproduction  and 
substances with endocrine disrupting properties are within the scope of this Directive if they are also 
carcinogenic  or  mutagenic.  The  prevention  and  protection  of  workers  is  ensured  through  a 
comprehensive system of measures including binding occupational exposure limit values, which are 
established and when necessary revised in the light of the most recent and relevant scientific data. 

180 

 
 
The  Pregnant  Workers  Directive  (92/85/EEC)  aims  to  implement  measures  to  encourage 
improvements in the safety and health at work of pregnant  workers and workers who have recently 
given  birth  or  who  are  breastfeeding.  As  regards  all  activities  involving  exposure  to  the  agents, 
processes  or  working  conditions  referred  to  in  the  non-exhaustive  list  of  Annex  I  (covering 
reproductive toxicity, category 1A, 1B or 2 as defined under the CLP Regulation as well as endocrine 
disrupting properties as this list is non-exhaustive), employers shall  assess the risks and any possible 
effect on the pregnancies or breastfeeding of the concerned workers and decide what measures should 
be taken - starting by avoiding exposure by temporarily adjusting the working conditions and/or the 
working hours of the worker concerned. If this is not technically and/or objectively feasible, or cannot 
reasonably be required, the employer shall take other required measures mentioned in the Directive.  

The Young People at Work Directive (94/33/EC) aims to protect young workers (under 18 years of 
age)  and  their  health  and  safety  at  work.  The  Directive  states  the  obligations  of  the  employer  to 
protect  health  and  safety  at  work  of  young  workers.  It  also  mentions  that  work  involving  harmful 
exposure to the physical, biological and chemical agents referred to in point I of the Annex is likely to 
entail specific risks for young people. The non-exhaustive list of agents included in the Annex of the 
Directive  covers  reproductive  toxicants  of  category  1A  and  1B,  and  the  three  carcinogenicity  and 
mutagenicity categories 1A, 1B and 2, which then could cover substances with endocrine disrupting 
properties. 

12 Water 
The  central  piece  of  water-related  legislation  in  Europe  is  the  Water  Framework  Directive  (WFD, 
2000/60/EC), which aims at protecting and enhancing freshwater resources with the aim of achieving 
good status of European water. This directive has two daughter directives: the Groundwater Directive 
(GWD,  2006/118/EC)  and  the  Environmental  Quality  Standards  Directive  (EQSD,  2008/105/EC) 
which  follow  from  obligations  under  the  WFD  and  are  directly  relevant  to  the  determination  of  the 
environmental objectives and standards specified under the WFD.  

The GWD  sets groundwater quality standards and requires measures to be taken to prevent or limit 
inputs of pollutants into groundwater and reverse upward trends. The directive refers to the indicative 
list of the main pollutants of the WFD (Annex VIII to Directive 2000/60/EC). 

The EQSD133 has been used to update the list of priority substances (PS), including priority hazardous 
substances  (PHS),  in  Annex  X  to  the  WFD,  for  which  Member  States  should  implement  necessary 
measures  to  reduce  (PS)  or  to  phase  out  (PHS)  discharges,  emissions,  and  losses.  Some  EDs  are 
included. The directive (Annex I) establishes Environmental Quality Standard (EQS) for PS, PHS and 
certain  other  pollutants  representing  limit  values  for  acceptable  concentrations  in  water  or  biota  for 
each  substance  for  inland  and  other  surface  waters  in  Europe.  It  also  requires  MS  to  establish  an 
inventory  of  emissions,  discharges  and  losses  of  the  substances  listed  in  the  Annex.  The  2013 
amendment not only revised the list of PS, which now includes 45 chemicals (of which 21 PHS), but 
also introduced a watch-list mechanism; the list itself was published in 2015 and updated in 2018 and 
2020134. The watch list is a list of potential water pollutants that should be monitored by the Member 
States to determine the risk they pose to the aquatic environment and whether EQS should be set for 

133Directive 2008/105/EC as amended by Directive 2013/39/EU 
134Commission Implementing Decisions (EU) 2018/240 and (EU) 2020/1161, respectively 

181 

 
 
                                                      
them. Until recently it included135￼. It now includes a number of other substances that are suspected 
or designated EDs. 

The  Marine  Strategy  Framework  Directive  (2008/56/EC)  aims  at  achieving  or  maintaining  a  good 
environmental  status  in  the  marine  environment,  including  as  regards  contaminants.  It  does  not 
address EDs specifically, but Member States are obliged to assess, in particular, the PS listed in the 
WFD, which include some EDs, and to meet the EQS for relevant PS in territorial waters (at least). In 
those waters, Member States  may select additional  contaminants,  and beyond  territorial waters they 
must  define  the  contaminants  to  be  assessed,  taking  account  of  the  PS.  The  MSFD  thus  allows 
Member States some freedom to decide which contaminants should be monitored. Decision 2017/848 
lays  down  criteria  and  methodological  standards  for  good  environmental  status.  The  standards  for 
contaminants  are  set  through  cooperation  in  the  Regional  Seas  Conventions,  when  not  already  set 
under the WFD.   

The  Urban  Waste  Water  Treatment  Directive  (UWWTD,  91/271/EEC)  aims  at  protecting  the 
environment  from  the  adverse  effects  of  urban  waste  water  discharges  and  discharges  from  certain 
industrial sectors. It concerns the collection, treatment and discharge of domestic wastewater, mixed 
wastewater,  and  wastewater  from  certain  industrial  sectors.  The  directive  mainly  focuses  on 
parameters  such  as  suspended  solids,  oxygen  demand,  and  some  chemicals  responsible  for 
eutrophication such as phosphorus and nitrogen but does not mention chemical micropollutants (and 
all the more does not specifically mention EDs), although some treatments are effective at removing 
some chemicals (Pistocchi et al., 2019). The directive has recently been evaluated136 and the follow-up 
is  likely  to  include  consideration  of  a  wider  range  of  chemical  pollutants,  such  as  pharmaceutical 
residues and microplastics.  

Finally,  the  Drinking  Water  Directive  aims  at  regulating  the  quality  of  water  intended  for  human 
consumption. The first DWD was adopted in 1998, and in 2018 the EC adopted a proposal for a recast 
of the DWD to improve the quality of drinking water and provide greater access and information to 
citizens, as a direct follow-up to the Right2Water European Citizen’s Initiative and of the REFIT of 
the  DWD137.  This  proposal  is  politically  agreed  by  the  European  Parliament  and  the  Council,  to  be 
adopted  and  published  by  the  end  of  2020.  To  address  growing  public  concern  about  the  possible 
effects  of  “emerging  pollutants”  (including  EDs)  on  human  health  through  drinking  water,  the 
proposal includes provisions for certain substances. It introduces standards for Bisphenol A and PFAS 
in drinking water, and a watch-list mechanism designed to ensure that MS pay particular attention in 
their risk  assessment to endocrine-disrupting substances, such as nonylphenol and  17-beta-estradiol, 
and that, where necessary, water suppliers monitor those substances and treat the water accordingly if 
its quality is considered to pose a risk to human health. Based on the risk assessments, management 
measures to prevent or control the risks identified should be taken to ensure the good quality of the 
water intended for human consumption. 

All pieces of water related legislation are closely interconnected, due to the water cycle: surface water 
quality is directly influenced by waste water quality and in turn has a direct impact on the quality of 
drinking water. A water FC was finalised in 2019138 which covered the WFD, the GWD, the EQSD as 
well as Directive 2007/60/EC on the assessment and management of flood risks. This FC is linked to 

135https://ec.europa.eu/jrc/en/science-update/updated-surface-water-watch-list-adopted-commission  
136https://ec.europa.eu/environment/water/water-urbanwaste/evaluation/index_en.htm  
137SWD(2016) 428  
138SWD(2019) 439 

182 

 
 
 
                                                      
the evaluation of the UWWTD, as the measures under the UWWTD are essential for the achievement 
of the WFD objectives.  

in 

Many of the actions being taken, planned or considered in the water policy area serve to support the 
objectives  of  the  Commission  Communication  “A  European  Union  Strategic  Approach  to 
the  Commission  Communication  “Towards  a 
Pharmaceuticals 
Comprehensive  European  Union  Framework  on  Endocrine  Disruptors”140  and 
the  Council 
Conclusions “Towards a Sustainable Chemicals Policy Strategy of the Union”141. They will also allow 
following up on new knowledge about the relevance of EDs for human health and new knowledge on 
the most appropriate monitoring approaches and methodologies.  

the  Environment”139, 

13 Chemical-product-waste interface 
Two  boundaries  define  the  interface  between,  on  the  one  hand,  horizontal  chemicals  and  product-
specific  legislation  and,  on  the  other  hand,  waste  legislation:  the  first  boundary  is  crossed  when 
products become waste (end-of life); the second when waste is recycled into secondary materials and 
products (end-of-waste). As long as substances are part of waste, they are regulated under the Waste 
Framework Directive.  Directive 2008/98/EC on waste (i.e. Waste Framework Directive) defines the 
hierarchy  of  waste  management,  which  prioritises  waste  prevention,  including  reduction  of  the 
hazardousness  of  wastes.  According  to  the  waste  hierarchy,  waste  generation  cannot  be  prevented, 
material recycling should have priority over thermal recovery and the last option should be the (safe) 
disposal  of  wastes  (incineration  or  landfilling).  Reuse  and  recycling  of  wastes  closes  the  material 
cycles  are  therefore  a  core  element  of  the  circular  economy.  From  the  point  of  view  of  waste 
legislation, the potential negative impacts of hazardous substances in material cycles are controlled by 
product-level restrictions, waste management rules (e.g. treatment requirements, traceability of waste 
streams) and provisions for end-of-waste criteria. Restrictions in products belong to the chemical (e.g. 
REACH)  and  to  product-specific  legislation  (e.g.  Restriction  of  Hazardous  Substances  –  RoHS 
Directive).  The  RoHS  Directive  2011/65/EU  sets  restrictions  on  the  use  of  certain  hazardous 
substances in electrical and  electronic equipment. In the prioritisation  of substances for inclusion  in 
the Annex II of the RoHS, EDs are given equally high priority as category 1 CMRs, to the extent they 
are listed as SVHC under REACH142. They are the only piece of product-level legislation restricting 
specific  substances  (e.g.  Annex  II  to  RoHS)  with  the  main  objective  of  facilitating  waste  treatment 
and recycling. Other product-level legislation mainly aims to ensure safety for human health and the 
environment during (primary) use of the product. 

Directive 2008/98/EC (Waste Framework Directive) establishes waste management and end of waste 
provisions.  Provisions  for  waste  management  act  as  a  filter  that  aims  to  clean/regenerate  material 
flows by separating unwanted compounds so that they can be re-used or re-purposed according to the 
needs  of  new  production  processes  or  products,  all  while  considering  potential  human  health 
(workers) and environmental implications.  

The properties which render waste hazardous are laid down in Annex III of the directive, which refers 
to  CLP  categories including specific target  organ toxicity (HP5), acute toxicity  (HP6),  carcinogenic 
(HP7),  mutagenic  (HP11),    reproductive  toxicants  (HP10)  and  ecotoxicity  (HP14),  with  specified 

139COM(2019) 128 
140COM(2018) 734 
141https://www.consilium.europa.eu/en/press/press-releases/2019/06/26/council-conclusions-on-chemicals  
142https://rohs.exemptions.oeko.info/fileadmin/user_upload/RoHS_Pack_15/4th_Consultation/Pack_15_Substan
ce_Review_Draft_Manual_Methodology_second_version_20190926.pdf 

183 

 
 
                                                      
concentration limits referring to the waste material for sub-hazard classes. For CMRs category 1A, 1B 
and  2  the  classification  of  mixtures  in  CLP  corresponds  to  the  concentration  limits  for  the 
classification  of  waste  as  hazardous.  However,  multiplying  factors  for  mixture  classification  (M-
factors)  applied  in  the  CLP  are  not  reflected  in  the  classification  of  hazardous  waste.  The 
identification  of  hazardous  waste  is  further  specified  in  the  list  of  waste  established  by  Decision 
2014/955/EU, although the list does not specify the hazardous property motivating the classification. 

Hazardous  waste  is  subject  to  stricter  controls  including  cradle-to-grave  traceability  and  the 
prohibition to dilute with other waste streams (Directive 2008/98/EC, Article 17 and 18). The quality 
of recycled materials can be controlled by setting specific end-of-waste criteria for placing secondary 
materials on the market. These are established at EU level or alternatively by Member States, in line 
with the general principles of Article 6, including no adverse environmental or human health impact. 
Specific end-of-waste criteria have been agreed for a few waste types (EC decisions), but not yet for 
major materials such as paper or plastics. In the absence of specific EU-level or national end-of-waste 
criteria,  case-by-case  decisions  are  made  by  competent  authorities  on  whether  a  certain  waste  has 
ceased to be waste (Article 6(4)) with implications for its handling. 

The Commission has identified four main issues at the interface between chemical, product and waste 
legislation,  which  act  as  barriers  to  the  achievement  of  the  objectives  of  the  circular  economy 
package:  the  presence  of  substances  that  are  no  longer  allowed  in  waste  and  recycled  products;  the 
lack  of  information  available  to  waste  operators  on  substances  of  concern  in  waste;  the  lack  of 
harmonised  rules  for  the  hazard  classification  of  chemical  mixtures  and  waste;  and  the  lack  of 
harmonised rules on end-of-waste. While these problems relate to all substances of concern and not 
specifically to EDs, several potential and identified EDs have been mentioned when illustrating those 
issues, owing to their widespread presence in articles and material flows, such as plastics, paper and 
textiles (Milieu Ltd et al., 2017) (sub study b). 

In response to the need to improve the information flow on the presence of SVHC in materials and 
waste  streams,  the  Commission  has  introduced  new  obligations  to  Member  States  under  the  Waste 
Framework  Directive.  Member  States  are  required  to  ensure  that  suppliers  of  an  article,  as  defined 
under REACH Article 33, provide information to ECHA on the presence of SVHC, as from 5 January 
2021.  The  information  shall  be  stored  in  a  database  maintained  by  ECHA  and  made  accessible  to 
waste treatment operators143. 

14 Other in-scope legislation 

  Detergents 

14.1
The  Detergents  Regulation  ((EC)  No  648/2004)  establishes  rules  designed  to  achieve  the  free 
movement of detergents and surfactants for detergents in the internal market while, at the same time, 
ensuring a high degree of protection of the environment and human health. The regulation focuses on 
the  biodegradability  of  surfactants,  their  restrictions  or  bans  on  grounds  of  biodegradability,  the 
labelling of detergents, including fragrance allergens, the limitations on the content of phosphates and 
other  phosphorus  compounds  in  detergents,  and  the  type  of  information  held  at  the  disposal  of  the 
Member States’ competent authorities and medical personnel. 

143Directive (EU)2018/851 amending Directive 2008/98/EC on waste 

184 

 
 
                                                      
According  to  the  Detergents  Regulation,  surfactants  and  detergents  containing  surfactants  that  meet 
the  criteria  for  ultimate  aerobic  biodegradation  (primary  biodegradability  of  at  least  80  %)  may  be 
placed  on  the  market  without  further  limitations  relating  to  biodegradability.  If  this  criterion  is  not 
met,  manufacturers  of  industrial  or  institutional  detergents  containing  surfactants,  and/or  of 
surfactants for industrial or institutional detergents, may ask for derogation. 

The Regulation is interconnected with CLP, REACH, Biocidal Product regulation and the Cosmetic 
Products Regulation. 

It does not have specific provision for the identification of EDs, however, provisions under REACH 
and  the  Biocidal  Products  Regulation  apply.  Moreover,  Annex  IV  on  the  complementary  risk 
assessment  for  surfactants  in  detergents  (applicable  to  Industrial  and  Institutional  detergents  that 
contain  surfactants  not  meeting  the  criterion  of  ultimate  biodegradability  set  in  the  Regulation,  and 
needing a derogation) states that if some metabolites are suspected for endocrine disrupting activity, it 
is recommended to determine if these have potential to result in adverse effects. 

  Fertilising Products  

14.2
The Regulation (EC) No 2003/2003 on Fertilisers has been repealed by the new Fertilising Products 
Regulation (EU) 2019/1009, which will apply from 16 July 2022. The new Regulation maintains the 
rules  of  optional  harmonisation,  where  a  manufacturer  can  choose  to  comply  with  the  Fertilising 
Products  Regulation  or  with  national  standards  based  on  the  principle  of  mutual  recognition.  Both 
Regulations interconnect with the REACH, CLP, PPP and Waste Regulations.  

The Regulations do not have specific provisions for EDs. Fertilising products will only be approved if 
under  normal  conditions  of  use  they  do  not  adversely  affect  human,  animal,  plant  health,  or  the 
environment. The safety of the constituent of the product should comply with the REACH regulation.  

Different  fertilising  product  functions  warrant  different  product  safety  and  quality  requirements 
adapted  to  their  different  intended  uses.  EU  fertilising  products  are  therefore  divided  into  different 
product  function  categories  (PFCs),  each  of  which  are  subject  to  specific  safety  and  quality 
requirements. 

The  information  requirements  should  ensure  that  the  safety  of  the  intended  use  of  the  fertilising 
product is demonstrated in a manner comparable to that of Regulation (EC) No 1107/2009 (PPP). 

In  the  event  manufacturers  have  reason  to  believe  that  an  EU  fertilising  product  which  they  have 
placed on the market presents a risk to human, animal or plant health, to safety or to the environment, 
they shall immediately inform the competent national authorities of the Member States in which the 
EU fertilising product is placed on the market, and shall cooperate with that authority to eliminate the 
risks posed by the product. Similarly, where a Member State has justifiable grounds for believing that 
a specific EC fertilising product, although satisfying the requirements of the Regulation, constitutes a 
risk  to  safety,  health  of  humans,  animals,  plants,  or  risk  to  the  environment,  it  may  temporarily 
prohibit  the  placing  on  the  market  of  that  fertilising  product  in  its  territory  or  make  it  subject  to 
special  conditions.  It  shall  immediately  inform  other  Member  States  and  the  Commission  thereof, 
giving the reasons for its decision, and the Commission shall adopt a decision on the matter.  

  Ecolabel Regulation  

14.3
The  objective  of  Regulation  (EC)  66/210  is  to  recognise  through  a  voluntary  scheme  products  and 
services meeting high environmental standards throughout their life-cycle. The ecolabel is in principle 
not awarded to goods containing substances meeting the criteria for classification as toxic, hazardous 

185 

 
 
to the environment, carcinogenic, mutagenic or toxic for reproduction (CMR), in accordance with the 
CLP regulation and not to goods containing substances referred to in Article 57 of REACH (Article 
6(6)). If substitutions are not technically feasible, derogations are possible, but may not be granted to 
substances  listed  in  the  REACH  Candidate  List  (established  via  REACH  Article  59(1))  present  in 
mixtures  or  in  (homogeneous  parts  of)  articles  at  > 0.1%  w/w  (Article  6(7)).  There  is  no  explicit 
reference to EDs, but EDs may be addressed by Article 6(6) and 6(7). Specific ecolabel criteria are 
developed  per  product  category  following  procedures  involving  the  European  Union  Ecolabelling 
Board,  the  Commission,  Member  States,  Competent  Bodies  and  other  stakeholders.  Most  product 
categories set specific provisions for the restriction of hazardous substances defined according to CLP 
and  SVHC  criteria.  Products  associated  with  domestic  wastewater  emissions  (e.g.  detergents, 
cosmetic products) include criteria for chronic aquatic toxicity.  

   General Product Safety Directive  

14.4
In  principle,  under  Directive  2001/95/EC  producers  are  obliged  to  only  place  safe  products  on  the 
market.  To  ensure  consumer  safety  and  health  protection,  market  surveillance  activities  are 
established by Member States authorities and  measures taken against products posing risk are to be 
notified  in  the  Rapid  Alert  System  for  dangerous  non-food  products  (Safety  Gate/RAPEX). 
Notifications  in  the  system  also  cover  chemical  risk.  The  Guidelines  of  the  system  (Decision 
2019/417) include a chapter on risk assessment. For chemicals there are specific instructions on how 
to  prepare  a  risk  assessment,  and  therefore  they  are  not  dealt  with  in  detail  in  these  guidelines. 
Nevertheless, they follow the same principles as for ‘normal’ consumer products. For products posing 
chemical risks, the Guidelines also indicate that the risk level of a product may be considered serious 
if it contains a chemical substance either banned or in a concentration above the limit established by 
European  legislation.  Therefore,  in  cases  where  measures  are  taken  against  products  containing  a 
chemical  substance  subject  to  a  restriction  contained  in  EU  Legislation,  a  notification  may  be 
submitted without a detailed risk assessment. 

In  general  terms,  the  GPSD  requires  producers  and  distributors  to  take  action  to  prevent  risk  to 
consumers when they become aware that a product that they have placed on the market poses risks 
and to inform competent authorities of the Member States thereof. Market surveillance authorities can 
seek to limit the marketing or use of a chemical substance or preparation.  

Where measures are taken against products for the presence of a chemical risk in one Member State, 
these  are  to  be  notified  in  Safety  Gate/RAPEX.  Except  in  justified  cases  as  explained  above 
notifications  must  be  accompanied  by  sound  risk  assessment  considering  the  risks  posed  by  the 
product  over  its  lifetime.  Risk  management  is  also  paramount  and  should  take  account  of  the 
quantities  placed  on  the  market.  For  all  notifications  made,  all  countries  of  the  network  (EU  + 
Norway, Iceland and Liechtenstein) are required to take appropriate follow up action and screen their 
market on the possible presence of the same product so as to ensure a safe single market.  

As  of  August  2020,  phthalates  and  bisphenol  A  are  the  only  substances  with  endocrine  disrupting 
properties that have been referred to in RAPEX for their restriction under REACH. 

  Seveso III Directive and Industrial Emission Directive 

14.5
The  Seveso  III  directive  (2012/18/EU)  aims  at  laying  down  the  rules  for  the  prevention  of  major 
accident  involving dangerous substances, and the limitation  of their  consequences for human  health 
and  the  environment.  It  does  not  contain  provisions  specific  to  EDs,  and  defines  "dangerous 
substances"  based  on  classification  and  volume:  for  human  health,  a  substance  classified  based  on 
acute toxicity and specific target organ toxicity (single exposure) might be considered as hazardous, 

186 

 
 
depending  on  the  volume,  whereas  for  environmental  health,  a  substance  classified  as  hazardous  to 
the  aquatic  environment  (categories  acute  1  or  chronic  1,  above  100  tonnes;  chronic  2  above  200 
tonnes) might be considered as hazardous. Therefore, the limitation to prevent and manage exposure 
to  EDs  linked  to  major  accident  are  both  linked  to  the  limitation  of  the  above-mentioned  CLP 
categories to identify EDs and the missing specific provisions in the Directive. 

The  Industrial  Emission  Directive  (2010/75/EU)  aims  at  ensuring  a  high  level  of  environmental 
protection and the improvement of environmental quality by laying down rules to prevent or to reduce 
emissions  into  air,  water  and  land  and  to  prevent  the  generation  of  waste  through  requiring  the 
application of Best Available Techniques (BAT) in installations. BATs are identified on a sector-by-
sector basis in what are called BAT reference documents (BREFs). One of the first steps in preparing 
a BREF is to agree what are the Key Environmental Issues to be addressed. The  Directive does not 
specifically address EDs, although if EDs are identified as a Key Environmental Issues they could be 
included in the BREFs. inclusion of hazardous substances as Key Environmental Issues is not based 
on  explicit  criteria  but  rather  refer  to  existing  regulatory  intervention  under  chemical  (e.g.  REACH 
restrictions) and water legislation (e.g. priority substances under the WFD)144. It is important to note 
that emission limit values set in this directive are only based on the BAT, not on health or ecotoxicity 
criteria. Moreover, to detect possible soil and groundwater pollution and to take appropriate corrective 
measures, the monitoring of soil and groundwater for relevant hazardous substances is also required. 

  Directive on air quality 

14.6
Two  directives  are  focusing  on  air  quality,  Directive  2008/50/EC  and  Directive  2004/107/EC.  The 
first one aims at defining and establishing objectives for ambient air quality in order to avoid, prevent 
or  reduce  harmful  effects  on  human  health  and  the  environment,  whereas  the  second  one  relates  to 
arsenic, cadmium, mercury, nickel and polycyclic aromatic hydrocarbons in ambient air.  None have 
specific provisions for EDs, but address air pollutants of toxicological concern. In the case of arsenic, 
cadmium,  mercury,  nickel  and  polycyclic  aromatic  hydrocarbons,  their  carcinogenic  potential,  not 
their endocrine disrupting potential, is the main source of concern.  

Ambient  air  quality  standards  (i.e.  maximum  allowed  concentration)  are  established  for  sulphur 
dioxide, nitrogen, dioxides and oxides of nitrogen, particulate matter (PM10 and PM2,5), lead, benzene, 
ozone and carbon monoxide in the context of Directive 2008/50/EC, and arsenic, cadmium, nickel and 
benzo(a)pyrene in the context of Directive 2004/107/EC. Member States should monitor air quality in 
their territory and should take measures to ensure that concentrations do not exceed the limit or target 
value. 

Those  air  quality  standards  are  based  on  WHO  guidelines  (WHO,  2005),  which  collect  available 
scientific  evidence  about  air  pollution  and  its  health  consequences  and  provide  indicative  levels  as 
guidance  for  reducing  the  health  impacts  of  air  pollution.  Member  States  are  required  to  take 
measures whenever there is exceedance of those air quality standards and to establish air quality plans 
to keep the exceedance period as short as possible. 

144See for example draft BREF for textile industry: https://eippcb.jrc.ec.europa.eu/sites/default/files/2020-
01/TXT_bref_D1_1.pdf 

187 

 
 
 
                                                      
  WTO rules 

14.7
With  respect  to  setting  rules  that  restrict  the  imports  of  chemicals,  materials  and  products,  the  EU 
must adhere to WTO rules, namely the Agreement on Technical Barriers to Trade (TBT agreement145) 
and, regarding pesticides, the Agreement on the Application of Sanitary and Phytosanitary Measures 
(SPS Agreement146). The aim of both agreements is to maintain the sovereign right of any government 
to provide the level of health protection it deems appropriate, but to ensure that these sovereign rights 
are  not  misused  for  protectionist  purposes  and  do  not  result  in  unnecessary  barriers  to  international 
trade.  Regulatory measures  must  not create technical barriers to trade, unless justified  by legitimate 
objectives, which include the protection of human health or safety, animal or plant life or health, or 
the  environment.    Under  the  SPS  agreement,  WTO  members  shall  ensure  that  their  sanitary  or 
phytosanitary measures are based on a scientific assessment, as appropriate to the circumstances, of 
the  risks  to  human,  animal  or  plant  life  or  health,  taking  into  account  risk  assessment  techniques 
developed  by  the  relevant  international  organizations.  For  example,  the  Codex  Committee  on 
Pesticide  Residues  is  responsible  for  establishing  Codex  Maximum  Residue  Limits  (MRLs)  for 
pesticide residues in specific food items or in groups of food or feed that move in international trade. 

Upon implementing regulatory measures that create a technical barrier to trade, members are obliged 
to submit at draft stage to the other members any legislation that could potentially contain technical 
barriers  to  trade  and  to  allow  a  reasonable  interval  between  the  publication  of  technical  regulations 
and their entry into force. 

WTO  rules  establish  a  procedure  for  members  to  raise  specific  trade  concerns  (STCs)  to  challenge 
measures  deemed  unnecessary  barriers  to  trade.  Most  STCs  raised  before  the  WTO  Committee  on 
Technical Barriers to Trade (TBT Committee) are discussed without escalating into formal disputes. 
A  relatively small  number  of disputes have  been  subject  to  the WTO  dispute  settlement  procedures 
(Holzer, 2018). 

145https://ec.europa.eu/growth/tools-databases/tbt/en/documents  
146https://www.wto.org/english/tratop_e/sps_e/spsagr_e.htm  

188 

 
 
 
 
 
 
                                                      
15 References 
ECHA, EFSA, and JRC (2018). Guidance for the identification of endocrine disruptors in the context 
of Regulations (EU) No 528/2012 and (EC) No 1107/2009. EFSA Journal, 16, 5311. 

EFSA Panel on Food Additives and Nutrient Sources added to Food (2012). Guidance for submission 
for food additive evaluations. EFSA Journal, 10, 2760. 

EFSA Panel on Food Contact Materials, Enzymes, and Flavourings and Processing Aids (2008). Note 
for  Guidance  for  the  Preparation  of  an  Application  for  the  Safety  Assessment  of  a  Substance  to  be 
used in Plastic Food Contact Materials. EFSA Journal, 6, 21r. 

EFSA  Panel  on  Food  Contact  Materials,  Enzymes,  and  Flavourings  and  Processing  Aids  (2015). 
Scientific  Opinion  on  the  risks  to  public  health  related  to  the  presence  of  bisphenol  A  (BPA)  in 
foodstuffs. EFSA Journal, 13, 3978. 

EFSA  Panel  on  Food  Contact  Materials,  Enzymes,  and  Flavourings  and  Processing  Aids  (2016). 
Recent  developments  in  the  risk  assessment  of  chemicals  in  food  and  their  potential  impact  on  the 
safety assessment of substances used in food contact materials. EFSA Journal, 14, 4357. 

EFSA  Panel  on  Food  Contact  Materials,  Enzymes,  and  Flavourings  and  Processing  Aids  (2019). 
Update  of  the  risk  assessment  of  di‐ butylphthalate  (DBP),  butyl‐ benzyl‐ phthalate  (BBP),  bis(2‐
ethylhexyl)phthalate (DEHP), di‐ isononylphthalate (DINP) and di‐ isodecylphthalate (DIDP) for use 
in food contact materials. EFSA Journal, 17, 5838. 

EMA  (2016).  Guideline  on  environmental  impact  assessment  for  veterinary  medicinal  products  in 
support of the VICH guidelines GL6 and GL38 (https://www.ema.europa.eu/en/documents/scientific-
guideline/guideline-environmental-impact-assessment-veterinary-medicinal-products-support-vich-
guidelines-gl6_en.pdf). 

Holzer, K. (2018). Addressing Tensions and Avoiding Disputes: Specific Trade Concerns in the TBT 
Committee. 

IPCS (2002). Global Assessment of the State-of_the-Science of Endocrine Disruptors, T. Damstra, S. 
Barlow, 
eds. 
(https://www.who.int/ipcs/publications/new_issues/endocrine_disruptors/en/). 

Bergman, 

Kavlock, 

Kraak, 

Van 

Der 

and 

G. 

A. 

R. 

Milieu Ltd, Ökopol, Risk & Policy Analysts, and RIVM (2017). Study for the strategy for a non-toxic 
environment 
Programme 
(https://ec.europa.eu/environment/chemicals/non-toxic/pdf/NTE%20main%20report%20final.pdf). 

Environment 

Action 

7th 

the 

of 

OECD  (2018).  Revised  Guidance  Document  150  on  Standardised  Test  Guidelines  for  Evaluating 
Chemicals for Endocrine Disruption (https://doi.org/10.1787/9789264304741-en). 

Pistocchi, A., Dorati, C., Grizzetti, B., Udias MoineloO, A., Vigiak, O., and Zanni, M. (2019). Water 
quality in Europe: effects of the Urban Wastewater Treatment Directive. 

SCCS  (2018).  SCCS  Notes  of  Guidance  on  for  the  testing  of  cosmetic  ingredients  and  their  safety 
evaluation  (10th  revision)  (https://op.europa.eu/en/publication-detail/-/publication/1d5f1653-38ce-
11e9-8d04-01aa75ed71a1/language-en/format-PDF). 

SCHEER  (2019).  Guidelines  on  the  benefit-risk  assessment  of  the  presence  of  phthalates  in  certain 
medical devicescovering phthalates which are carcinogenic, mutagenic, toxic to reproduction (CMR) 
or have endocrine-disrupting (ED) properties (doi: 10.2875/784367). 

Quality 
WHO 
(http://www.euro.who.int/__data/assets/pdf_file/0005/78638/E90038.pdf?ua=1). 

Guidelines 

(2005). 

Global 

Air 

Update 

2005 

189 

 
 
 
 
 
 
 
Annex 5A. Case Study: 3-benzylidene camphor (3-BC) 

1  Case  study  factsheet:  overview  of  concerns  for  human  health 

and environment and main regulatory intervention 

Product 
(possible 
sources) 

types 
exposure 

Cosmetic products (e.g. sunscreens)* 

* the use has been restricted or otherwise regulated in the EU. 

Exposure  pathways 
of  concern  (human 
and environment) 

Human exposure through skin absorption. 
Environmental  exposure  through  domestic  wastewater  discharges,  wash-off 
from bathers, and direct emissions from cosmetics production sites. 

Concerns  for  human 
health  and/or 
the 
environment 

In  humans:  developmental  (teratogenicity)  effects,  likely  mediated  by 
estrogenic activity.  
In wildlife: endocrine mediated reproductive toxicity with serious and long-
lasting effects on aquatic species. 

Regulatory  hazard 
and risk assessment 

  1998 - SCCNFP favourable opinion on use in cosmetics at a maximum 
concentration  of  2%  as  proposed  by  submitter.  No  ED  specific 
assessment was required. 

  2013 (June) – SCCS opinion: not safe for use in cosmetics based on risk 
assessment with insufficient margin of safety due to teratogenic effects. 
Studies showing effects likely  caused by an ED mode of action (MoA) 
and relevant for human health used as supporting evidence. 

  2016  (February)  –Proposal  from  Germany  for  identification  SVHC  for 

ED effects in the environment. 

  2018  (December)  –  Identification  as  a  substance  of  very  high  concern 
due to its endocrine disrupting properties in the environment in line with 
the WHO definition of an endocrine disruptor and REACH Article 57(f), 
based on a dossier submitted by Germany 

Risk  management 
measures 

  1988 - Submitted for assessment for cosmetics use  
  1998  -  Listed  in  the  Cosmetics  Directive  Annex  VII  for  use  up  to  2% 

based on SCCNFP opinion (removed in 2015) 

  2011  France  bans  use  in  cosmetics  based  on  developmental  effects  and 

potential endocrine MoA 

  2015  (July)  Cosmetics  use  (UV  filter  and  UV  absorber)  banned  EU-

wide147, with effect from 18 February 2016 
2019  (February)  Added  to  REACH  candidate  list,  but  no  further 
regulatory  management  measures  proposed  for  the  time  being  since  the 
substance is not registered under REACH and there is no information on 

147Commission Regulation (EU) 2015/1298 of 28 July 2015 amending Annexes II and VI to Regulation (EC) 
No 1223/2009 of the European Parliament and of the Council on cosmetic products 

190 

 
 
 
 
 
                                                      
uses  falling  under  REACH.  As  from  16  July  2019,  obligation  for 
producers and importers to notify ECHA if an article contains > 0.1% of 
3-BC and to inform downstream users and consumers. 

2  Substance profile 
The  main  use  of  3-Benzylidene  camphor  was  in  cosmetics  as  an  effective  UV  absorber  previously 
used in sunscreen and whitening products. It is highly hydrophobic and insoluble in water.  There is 
no evidence about other uses in the EU since the substance is not registered under REACH or other 
regulations.  

2.1

  Exposure pathways of concern  

Human Exposure 

As a UV filter used in sunscreen and skin whitening products, dermal absorption is the main human 
exposure pathway of concern. 

Environmental Exposure 

UV  filters  can  enter  the  aquatic  environment  indirectly  via  wastewater  treatment  plants  (washing, 
bathing, laundering), and directly from recreational activities such as swimming and bathing. Due to 
its hydrophobicity it has high potential to accumulate in organic matter and in organisms' lipid tissues. 
It is considered to be not readily biodegradable based on available QSAR predictions (ECHA 2016). 

2.2

  Effects on human health and the environment 

Human Hazard 

Multiple  hormonal  activities  of  3-BC  have  been  reported  in  vitro:  estrogenic  and  anti-estrogenic 
effects as well anti-androgenic activities. Estrogenic activity has been observed in vivo in rats and fish 
and the likely cause of developmental (teratogenicity) effects observed in rats (SCCS 2013).  

Environmental Hazard 

In  vivo  fish  assays  indicate  that  3-BC  or  its  metabolites  cause  serious,  irreversible  and  long-lasting 
adverse  effects  (decreased  fertility  and  fecundity)  in  fish  (that  are  population-relevant)  due  to  an 
endocrine mode of action (ECHA 2016).   

191 

 
 
 
 
 
Figure 16.1. 3-BC case study: illustration of applied provisions across legislation 

3  3-BC and structurally similar UV filters in EU legislation 

3.1

  Regulating 3-BC in cosmetics legislation 

Submission I on the UV-filter 3-benzylidene camphor with the chemical name 3-benzylidenebornan-
2-one was submitted by COLIPA in 1988. The Scientific Committee on Cosmetic Products and Non-
Food products intended for consumers (SCCNFP) adopted an opinion in January 1998 (1374/1998). 
Data on toxicological endpoints specifically related to potential endocrine effects were not available at 
that  time  and  consequently  not  assessed.  The  SCCNFP  evaluation  was  carried  out  for  a  proposed 
maximum  concentration  of  2%  indicated  by  the  dossier  submitter.  The  favourable  opinion  was 
justified by a sufficient margin of safety determined based on a NOAEL of 20 mg/kg/day from a 90-
day oral toxicity study in rats. The corresponding adverse effect was an elevated level of plasma lipids 
in female rats (SCCNFP opinion)  

The  substance  was  then  included  in  Annex  VII,  part  1  n.19  of  the  Cosmetics  Directive  (“List  of 
permitted UV filters which cosmetic products may contain”) in a concentration up to maximum 2%.  

In  October  2011,  the  French  authorities  notified  the  Commission  that  the  Agence  Française  de 
Sécurité  Sanitaire  des  Produits  de  Santé  (AFSSAPS),  had  adopted  a  decision  prohibiting  cosmetic 
products containing 3-BC as a safeguard measure in accordance with the provisions of Article 12 of 

192 

 
 
 
 
 
the Directive 76/768/EEC, which preceded the Cosmetic Products Regulation currently in place. The 
safeguard measure requires the Member State, if it considers that a hazard to health from the use of a 
cosmetic  product  exists  although  complying  with  the  requirements  of  the  Directive,  to  inform 
immediately the Commission  and other Member States. If the  measure is justified, the Commission 
proposes to extend the measure to the whole of the EU. If it is not justified, the action taken by the 
Member State has to be revoked. 

The  AFSSAPS  considered  the  hazard  characterisation  for  this  substance  incomplete.  In  addition,  it 
questioned  assumptions  in  the  exposure  characterisation  and  the  determination  of  the  no  observed 
adverse  effect  level  (NOAEL).  Using  a  higher  cutaneous  absorption  rate  and  a  lower  NOAEL  (15 
mg/kg/day)  from  an  existing  teratogenicity  study,  the  risk  assessment  resulted  in  an  insufficient 
margin of safety. Finally, as endocrine disrupting effects were observed in new studies published in 
the  scientific  literature  after  1998,  the  French  authorities  considered  that  it  was  not  possible  to 
conclude that there was no risk to humans from the use in cosmetics. 

In response to the initiative taken by the French authorities and as foreseen in Directive 76/768/EEC, 
in 2013 the Commission tasked the SCCS with re-evaluating the safety of 3-BC for use as a UV filter 
in cosmetic products at a concentration of up to 2.0%. The task had to take into account the scientific 
data provided as well as any additional scientific concern related to its potential endocrine disrupting 
properties for humans. The toxicological evaluation was based on the previous SCCNFP opinion from 
1998 (1374/96) and on the dossiers I, II, III and IV on the UV-filter 3-benzylidene camphor with the 
chemical  name  3-benzylidenebornan-2-one  submitted  by  COLIPA  respectively in  1988,  1991, 1992 
and  1994.  The  submitted  files  contained  only  summaries  of  the  experimental  studies;  original  data 
were not made available to the scientific committee (Opinion SCCS/1513/13).  

The SCCS concluded in its opinion on 3-BC published in 2013 that the use of this substance up to 2 
%  in  cosmetic  products  is  not  safe.  The  opinion  in  particular  re-evaluated  a  key  study  from  the 
previous  opinion  1374/98.  The  conclusion  was  justified  by  an  insufficient  margin  of  safety  using  a 
NOAEL  derived  from  an  oral  study  submitted  before  the  1998  opinion.  The  NOAEL  of  15  mg/kg 
bw/day  as  proposed  by  AFSSAPS  was  used  from  evidence  of  embryo-toxicity  at  50  mg/kg  bw/day 
and above in a developmental (teratogenicity) toxicity study with rats very similar to OECD TG 414 
(SCCS,  2013).  According  to  the  SCCS,  the  development  of  the  effects  may  be  associated  with  the 
maternal  toxicity  present  at  50  mg/kg  bw/day.  The  SCCS  did  not  explicitly  link  the  effects  to  an 
endocrine mode of action. 

The mandate given by the Commission to the SCCS included the assessment of potential endocrine 
disrupting properties.  The SCCS looked at nine in-vitro and in-vivo studies published between 2001 
and  2009  in  the  scientific  literature.  Some  of  the  studies  indicated  endocrine  activity  of  3-BC  or 
endocrine-mediated  effects.  Altered  sexual  behaviour  and  modification  of  the  oestrus  cycle  were 
observed in one study with rats at dose levels lower than for teratogenicity. The SCCS, however, saw 
shortcomings  in  the  available  studies  and  a  need  to  confirm  the  results.  In  particular,  not  all 
parameters  necessary  to  assess  comprehensively  the  results  were  reported  in  the  academic  studies 
published in scientific journals. Because of that, the evidence for endocrine disruption was used only 
as supporting evidence in the risk assessment of 3-BC. 

Based  on  the  teratogenic  effects  observed  and  due  to  a  margin  of  safety  below  100,  the  SCCS 
concluded that the use of 3-BC as a UV filter in cosmetic products in a concentration up to 2% is not 
safe.  In  February  2015,  the  Standing  Committee  on  Cosmetic  Products  voted  in  favour  of  the 
Commission’s  proposal  to  prohibit  the  use  of  3-BC  as  UV  filter  and  UV  absorber  in  cosmetic 

193 

 
 
products by deleting it from Annex VI (authorised list of UV filters) and adding it to Annex II (list of 
substances prohibited in cosmetic products) to Regulation (EC/1223/2009). 

  Regulating 3-BC under REACH 

3.2
3-BC is not registered under REACH. It is hence should not be manufactured in or imported into the 
EU in quantities above 1 tonne per year per legal entity. Furthermore, there are no indications that it is 
imported  into,  manufactured  or  used  in  the  EU.  Due  to  the  substance  not  being  registered,  a 
registration dossier with test data is not available. 

In  2015  Germany  submitted  its  intention  to  identify  3-BC  as  SVHC,  together  with  the  structurally 
similar 4-methylbenzylidene camphor (4-MBC). Considering the number of individual notifications in 
ECHA’s  C&L  Inventory  database  (as  cat.  2  reproductive  toxicant)  the  Risk  Management  Option 
Analysis (RMOA) submitted in 2015 concluded that 3-BC might be commercially relevant in the EU.  
However,  notifications  for  self-classification  do  not  reveal  whether  a  substance  is  currently  on  the 
market  in  the  EU  or  used.  The  RMOA  hypothesised  that  uses  other  than  cosmetics  could  lead  to 
environmental emissions. Therefore, risk management under REACH was judged necessary for other 
applications than cosmetics (RCOM 2015).  

The  proposal  for  identification  as  an  SVHC  (Annex  XV  report)  was  submitted  by  Germany  in 
February 2016. However, the Member State Committee (MSC)  did not reach  unanimous agreement 
on  this  proposal.  Following  the  provisions  of  REACH,  in  case  where  there  is  no  consensus  in  the 
Member  State  Committee  on  the  SVHC  identification,  a  decision  has  to  be  taken  by  the  European 
Commission. Hence, the dossier was forwarded to the Commission.  

According  to  Commission  Implementing  Decision  (EU)  2018/2013),  the  available  data  from  key 
scientific studies reported in the supporting document of the MSC majority opinion (e.g. Holbech et al 
2002, Kunz et al 2006b) demonstrate an endocrine-mediated mode of action of 3-BC causing serious, 
irreversible and long-lasting effects on fish fecundity relevant for wildlife populations. The decision 
further  concludes  that  the  fact  that  the  adverse  effects  on  fish  fecundity  were  observed  in  the  key 
study at low concentration levels strengthens the concern.  

The minority views in the MSC pointed to the legislative vacuum due to the lack of a Commission 
definition on EDs for environment (i.e. at that time, the Commission was still working on the criteria 
for  EDs  under  the  BPR  and  PPPR),  to  issues  of  reliability  of  the  key  study  (i.e.  effects  observed 
before exposure in some of the replicates, loss of test substance during the test).  

In  its  decision,  the  Commission  concluded  that  3-BC  fulfils  the  criteria  for  Article  57  (f).  In  other 
words it is a substance with endocrine disrupting properties for which there is scientific evidence of 
probable  serious  effects  for  the  environment,  which  gives  rise  to  an  equivalent  level  of  concern  as 
substances with properties listed in points [(a) to (e)] of Article 57 of the REACH regulation.   

Having  obtained  a  favourable  opinion  from  the  REACH  Committee  by  a  qualified  majority,  the 
decision was  adopted  in December 2018. In January 2019, 3-BC was included in the candidate list, 
which triggered the following obligations: 

  Producers or importers of articles must notify ECHA if their article contains 3-BC, if 
it  is  present  in  the  article  above  0,1%  and  the  quantity  of  3-BC  in  the  imported  or 
produced article is above 1 tonne per year (REACH Article 7(2)) 

194 

 
 
 
  Suppliers  of  3-BC,  or  of  mixtures  containing  the  substance,  must  provide  their 

customers with a Safety Data Sheet (REACH Article 31(1) and Article 31(2)). 

  Suppliers of articles must inform downstream users, and on request consumers, if the 
substance is present in an article at a concentration > 0.1 % (REACH Article 33) 

Further risk management measures for 3-BC were not considered to be necessary for the time being 
since 3-BC is not registered under REACH and since there are indications that the substance is not put 
on the market or used in the EU above the quantity of 1 tonne per year per legal entity. Nevertheless, 
information  resulting  from  the  legal  obligations  effective  as  from  16  July  2019  and  linked  to  the 
SVHC  identification  of  3-BC  and  its  candidate  listing  can  serve  to  determine  whether  further  EU-
wide risk regulatory measure (e.g. a restriction) is warranted. However, up to now, no notification of 
an imported or produced article containing 3-BC has been submitted to ECHA. 

  Status of structurally similar UV filters 

3.3
There  are  five  UV  filters  in  Annex  VI  to  the  Cosmetic  Products  Regulation  containing  a  camphor 
moiety.  Considering  that  some  of  them  have  received  attention  by  the  scientific  community  and  by 
regulators  for  their  potential  endocrine  disrupting  activity,  it  is  useful  to  review  their  status  for  the 
purpose of this case study. However, up to now, no regulatory body has identified them as endocrine 
disruptor at national or EU level. Furthermore, it is uncertain whether all substances with a camphor 
moiety have endocrine disrupting propertiess (Axelstad, 2013). 

Three  of  the  five  UV  filters  share  the  benzylidene  camphor  sub-structure:  4-methyl  benzylidene 
camphor  (4-MBC),  benzylidene  camphor  sulphonic  acid,  and  polyacrylamidomethyl  benzylidene 
camphor (entries 9, 11 and 18 of Annex VI to the Cosmetic Products Regulation), although the latter 
is  a  polymer.  The  other  two  share  the  camphor  groups  in  their  structure:  camphor  benzalkonium 
methosulfate and terephthalyidene dicamphor sulfonic acid (entries 2 and 7 of Annex VI).  

Only for 4-MBC is there information that the substance is on the EU-market since it was registered 
under  REACH  in  2018.  No  information  is  available  on  whether  polyacrylamidomethyl  benzylidene 
camphor is used in the EU. The other three UV-filters are not registered under REACH and hence are 
either not used in the EU or not on the EU market in quantities above 1 tonne per year per legal entity. 
The database on Substances in Products in Nordic Countries (SPIN148) either does not have data on 
the substances or indicates no use of the substance in products. 

4-MBC  is  listed  in  Annex  VI  based  on  the  2008 opinion of  the  Scientific  Committee  on  Consumer 
Products (SCCP) for safe use in sunscreens up to a maximum concentration of 4% w/w as indicated 
by  the  dossier  submitter.  Safety  concerns  related  to  endocrine  activity  were  first  voiced  in 2000.  In 
2001  the  SCCNFP  was  tasked  to  assess  organic  UV  filters,  including  4-MBC,  used  in  cosmetic 
sunscreen products for their estrogenic activity and concluded that none have the potential to affect 
human health (SCCNFP 2001). Upon a request of the Danish authorities the dossier for 4-MBC was 
reopened and additional data were submitted by industry in February 2004. The SCCP considered the 
information  provided  incomplete  and  requested  further  data  with  urgency  (SCCP  2004  opinion).  In 
the  following  opinion  from  2006,  the  SCCP  then  addressed  questions  related  to  potential  thyroid-
related endocrine effects in  humans. Once  more, the opinion was inconclusive, ending in additional 
test data requirements, stating that questions raised in 2004 had not been addressed by the additional 

148http://www.spin2000.net 

195 

 
 
 
                                                      
data  provided  by  the  submitter.  Finally,  in  2008  the  SCCS  issued  a  final  opinion  concluding  that 
presently  the  safe  use  of  a  maximum  concentration  of  4%  of  4-MBC  in  sunscreens  could  be 
established. A sufficient margin of safety for this concentration limit was established from a NOAEL 
derived  from  observed  thyroid  effects  in  a  90-day  oral  study  with  rats  and  from  a  revised  exposure 
level based on toxicokinetic information from the submitter in 2004. 

Due to the structural similarity, 4-MBC was considered for the SVHC identification due to its effects 
on  the  environment  together  with  3-BC  in  the  RMOA  completed  by  Germany  in  February  2016. 
However,  the  dossier  for  SVHC  identification  of  4-MBC  was  withdrawn  in  June  2016,  pending  its 
further elaboration149. Hence, 4-MBC has not been identified as an SVHC with ED properties for the 
environment.  Subsequently,  it  was  registered  under  REACH  in  2018,  for  use  in  cosmetic/  personal 
care products (https://echa.europa.eu/registration-dossier/-/registered-dossier/25426).  

to  6% 

in  1994 

in  cosmetics 

(benzylidene  camphor 

The other two benzylidene camphor UV filters listed in Annex VI were approved for use as UV filters 
sulphonic  acid)  and  1996 
up 
(polyacrylamidomethyl  benzylidene).  Similarly,  terephthalylidene  dicamphor  sulphonic  acid  was 
approved  in  1994  up  to  10%.  No  data  addressing  endocrine  disrupting  properties  are  available  for 
these substances or have been published. In 2013 an assessment by the Danish Centre for Endocrine 
Disrupters assessing the endocrine disrupting potential of 23 UV-filters with regard to human health 
and  ecotoxicological  concerns  concluded  that  for  these  substances  there  is  no  information  and  no 
scientific  opinion  of  EC  scientific  committees  addressing  endocrine  disrupting  properties  or 
reproductive toxicity. 

The  remaining  substance  containing  a  camphor  group,  camphor  benzalkonium  methosulfate  was 
evaluated by the SCCP in 2006 and in 2008. It is currently approved for use as a UV filter in cosmetic 
products  up  to  3%  (SCCP  1202/08).  The  margin  of  safety  was  calculated  using  a  NOAEL  derived 
from observed effects on the digestive tract in a 90-day oral study on rats. Reproductive toxicity was 
assessed but did not drive the risk assessment as minor uterotrophic effects observed in-vivo were not 
considered toxicologically relevant.  

In  the  review  of  the  Cosmetic  Products  Regulation  with  regard  to  substances  with  endocrine-
disrupting properties (COM(2018) 739), the Commission committed to establishing a priority list of 
potential endocrine disruptors in cosmetics for their subsequent safety assessment in view of possible 
bans/restrictions.  A  priority  list  of  28  potential  EDs  in  cosmetics  was  consolidated  in  early  2019 
following input provided by stakeholders150. Fourteen substances were prioritised into Group A, to be 
treated with higher priority because substance evaluation under REACH concluded that the substance 
is an ED or because an evaluation under REACH is ongoing. The list includes 4-MBC. 

The  Commission  launched  a  public  call  for  data  from  May  to  October  2019  on  the  14  Group  A 
substances.  In  view  of  the  quality  of  data  received  and  SCCS’s  capacity,  the  Commission  sent 
mandates  to  the  SCCS  in  January  2020  to  evaluate  5  substances  (3  of  which  are  UV  filters151).  If 
needed, the Commission will take appropriate action to prohibit or restrict the use of these different 
substances in cosmetics. 

149https://echa.europa.eu/documents/10162/22837890/msc-48_meeting_minutes_en.pdf/314824ca-fd22-4d96-
ae8d-3ba2050341f7 
150https://ec.europa.eu/growth/sectors/cosmetics/products/endocrine_en 
151Octocrylene, Homosalate and Benzophenone-3 

196 

 
 
                                                      
As  regards  the  remainder  of  the  9  Group  A  substances,  which  includes  4-MBC,  safety  information 
provided  during  the  call  for  data  was  incomplete,  thereby  stakeholders  have  been  invited  to 
complement their submission during 2020. The Commission will then proceed to mandate the SCCS 
with a second wave of another 5 substances in 2021, which will include 4-MBC.  

4  Comments on fitness check evaluation criteria 

Comments  on 
coherence 

Comments  on 
effectiveness 

  Different regulatory approaches applied for human health (Cosmetic Products 
Regulation)  and  environmental  concerns  (REACH  Regulation).  REACH 
applied a generic risk approach for identification as SVHC with effects to the 
environment, which is eventually followed up by  risk management measures 
based  on  specific  risk  or  risk-benefit  approach  (REACH  authorisation  or 
restriction).  The  Cosmetic  Products  Regulation  applies  risk  assessment  to 
conclude on potential risk to human health.  

  Cosmetics use banned in France in 2011, in the EU from 2016. 
  There are several structurally similar UV filters in Annex VI to the Cosmetic 
Products  Regulation.    These  substances  have  been  assessed  at  some  point  in 
time for their safety (human health) but have not been evaluated explicitly for 
potential  endocrine  disrupting  properties  in  in  the  context  of  the  Cosmetic 
Products  Regulation.  However,  available  data  indicate  only  for  one  of  the 
substances (4-MBC) that it is placed on the EU market. If there is a potential 
risk  to  health  or  should  new  data  be  available,  Article  31  is  triggered,  and  a 
new risk assessment has to be carried out for 4-MBC.  

  Since the 1998 favourable opinion of the SCCNFP on 3-BC, new evidence on 
estrogenic mode of action from in-vitro and in-vivo studies motivated France to 
revisit  the  1998  assessment.  By  reconsidering  specific  assumptions  in  key 
studies  already  reported  in  the  previous  assessment  (higher  absorption  factor, 
lower  NOEAL)  the  result  went  in  the  opposite  direction.  The  2013  SCCS 
opinion confirmed the new assessment and concluded that 3-BC is not safe for 
use  in  cosmetics  at  2%.  Consideration  of  endocrine  disrupting  potential  on 
human health was used as supporting evidence for the conclusion.    

  Triggering  the  safeguard  clause  by  French  authorities  led  to  an  EU  wide 

restriction of 3-BC in cosmetic products as foreseen in legislation.  

  Evidence  of  effects  of  3-BC  from  in-vivo  fish  studies  was  sufficient  for  the 
identification  of  3-BC  as  SVHC  under  REACH  with  ED  properties  for  the 
environment.  

  The  SVHC  identification  under  REACH  led  to  notification  obligations  for 
importers and producers that allow better monitoring of whether articles with 
3-BC are on the market and how the substance is used in articles.  

  The  obligation  under  REACH  to  register  substances  above  1  tonne  per  year 
allows to monitor whether a substance is manufactured in the EU or imported 
and what are the uses of the substance. This information helps to decide on and 
to prioritise regulatory action. 

197 

 
 
 
 
Comments  on 
efficiency 

Comments  on 
EU added value 

  Data from the scientific domain have been an integral part of and valuable for 
the  ED  assessment.  However,  studies  do  not  always  report  all  parameters 
necessary  to  comprehensively  assess  the  results,  which  hampers  their  use  in 
regulatory risk assessments. 

  4-MBC  has  been  assessed  under  REACH  for  ED  properties  for  the 
environment;  however,  the  responsible  committee  did  not  identify  the 
substance  as  SVHC  as  the  dossier  was  withdrawn  by  the  dossier  submitter.  
Other  structurally  similar  UV  filters,  which  are  either  not  used  in  the  EU  or 
only  in  low  quantities,  have  not  yet  been  evaluated  as  regards  their  ED 
properties.  This  might  at  least  partly  due  to  limited  test  data  in  combination 
with  the  ban  on  animal  testing,  which  hampers  the  ability  of  SCCS  to  reach 
conclusive opinions.  

  Procedures for assessing human and environmental safety are in two different 
(Cosmetic  Products  Regulation  and  REACH, 

legislation 

pieces  of 
respectively) 

  Different  risk  management  measures  in  place  for  cosmetics  between  2011  to 
2016  in  France  and  the  rest  of  the  EU.  The  mechanism  for  feeding  back  a 
conclusion from an MS to the EU has worked and the substance is regulated at 
EU level since 2016. 

  Concerning  hazard  identification,  as  from  January  2019,  3-BC  was  identified 
as an SVHC, based on being an endocrine disruptor for the environment, at EU 
level  under  the  REACH  Regulation.  Information  resulting  from  the  legal 
obligations linked to this SVHC identification can serve to determine whether 
further and EU-wide risk regulatory measures (e.g. a restriction) are warranted.  

198 

 
 
5  References 

Commission Implementing  Decision  (EU) 2018/2013  of 14 December 2018 on the identification of 
(3-benzylidene  camphor)  as  a 
1,7,7-trimethyl-3-(phenylmethylene)bicyclo[2.2.1]heptan-2-one 
substance  of  very  high  concern  pursuant  to  Article  57(f)  of  Regulation  (EC)  No  1907/2006  of  the 
European Parliament and of the Council. 

Axelstad M, Hass U, Lund Kinnberg K, Bjerregaard P, 2013. Assessment of the endocrine disrupting 
potential  of  23  UV-filters.  Danish  Centre  for  Endocrine  Disruptors.  http://www.cend.dk/files/UV-
filter-rapport-28022013_40s388pi.pdf 

ECHA. 
https://echa.europa.eu/registry-of-svhc-intentions/-/dislist/details/0b0236e180e4b445 

2016.  REACH 

intentions 

registry 

SVHC 

until 

of 

outcome 

ECHA. 
https://echa.europa.eu/registry-of-svhc-intentions/-/dislist/details/0b0236e180e47ae7 

2016.  REACH 

intentions 

registry 

SVHC 

until 

of 

outcome 

(3-BC). 

(4-MBC). 

ECHA. 2016. Support Document for SVHC listing as ED for environment. 

Hass U, Christiansen S, Axelstad M, Boberg J, Andersson AM, Skakkebæk NE, Bay K, Holbech H,  

Holbech, H., Nørum, U., Korsgaard, B., Bjerregaard, P., 2002. The chemical UV-filter 3benzylidene 
camphor causes an oestrogenic effect in an in vivo fish assay. Pharmacology and Toxicology 91, 204-
208. 

Kinnberg KL, and Bjerregaard P (2012).  Evaluation of 22 SIN List 2.0  substances according  to the 
Danish proposal on criteria for endocrine disrupters. 

Kunz, P.Y., Gries, T., Fent, K., 2006b. The ultraviolet filter 3-benzylidene camphor adversely affects 
reproduction in fathead minnow (pimephales promelas). Toxicological Sciences 93, 311-321. 

MS  (Germany)  REACH  Competent  Authority.  2015.  Risk  Management  Option  analysis  -  Intention 
for  SVHC  listing  (3-BC  and  4-BC).  https://echa.europa.eu/documents/10162/a9b3a495-e225-b072-
ec26-6ac0971ee7c5 

REACH  MS  Competent  Authority  (Germany).  2016.  Annex  XV  Report  –  Proposal  for  SVHC 
https://echa.europa.eu/documents/10162/cedbd042-fa1d-8332-59ea-
identification 
73425761d313 

(3-BC) 

REACH  MS  Competent  Authority  (Germany).  2016.  Annex  XV  Report  –  Proposal  for  SVHC 
https://echa.europa.eu/documents/10162/824709dd-dda0-fd1d-0ae1-
identification 
2d28aba799cd 

(4-MBC). 

SCCNFP. 2001. Opinion on the evaluation of potential estrogenic effects of UV-filters adopted by the 
2001. 
SCCNFP 
https://ec.europa.eu/health/scientific_committees/consumer_safety/opinions/sccnfp_opinions_97_04/s
ccp_out145_en.htm 

meeting 

Plenary 

during 

June 

17th 

the 

12 

of 

SCCNFP.  1998.  Opinion  of  the  Scientific  Committee  on  cosmetic  products  and  non-food  products 
intended for consumers concerning 3-benzylidenebornan-2-one. XXIV/1374/98. 

SCCP. 
https://ec.europa.eu/health/ph_risk/committees/04_sccp/docs/sccp_o_141.pdf 

4-methylbenzylidene 

2008.  Opinion 

camphor 

on 

(4-MBC). 

SCCP/1184/08. 

199 

 
 
on 
SCCS 
/publication/1c6a44ae-b016-4c78-b5c1-e03e607734e7/language-en 

Opinion 

3-BC. 

2013 

https://publications.europa.eu/en/publication-detail/-

200 

 
 
 
Annex 5B. Case Study: bis(2-ethylhexyl) phthalate (DEHP) 

1  Case  study  factsheet:  overview  of  concerns  for  human  health 

and environment and main regulatory intervention 

Product 
(possible 
sources) 

types 
exposure 

Exposure  pathways 
of  concern  (human 
and environment) 

-  Toys  and  childcare  articles  (plasticised  material)  including  food  contact 
materials * 
- Cosmetic products * 
- Products containing plasticised  materials such as building materials (floor 
coverings,  wall  paper,  sealants,  wiring)  and  various  other  articles  made  of 
plasticised materials, e.g. bicycle handles, covers for cell phones and tablets, 
children’s wrist watches,  gloves, school bags, PVC  tape,  rubber boots, rain 
coats, plastic sandals, bags, oilcloth and dinner mats, tools, synthetic leather 
furniture, sex toys and erasers (some exemptions apply e.g. for industrial or 
agricultural use) **  
- Other food contact materials *** 
- Medical devices **** 

*  Products  for  which  placing  on  the  market  has  been  restricted  in  the  EU 
(before May 2020)  
** Products for which placing on the market is restricted from 7th July 2020. 
This  restriction  targets  mainly  imports  since  EU  companies  would  require 
since 21 August 2013 an authorisation for the use of DEHP. 
***  Product  for  which  placing  on  the  market  is  allowed  for  certain 
conditions of use and associated restrictions 
****  Products  for  which  placing  on  the  market  will  be  allowed  under  new 
conditions  and  restrictions,  from  May  2021  for  medical  devices  and  from 
May 2022 for in vitro diagnostic medical devices. 

The general population is exposed to phthalates via different routes and from 
different sources. Oral exposure occurs from ingestion of food and dust, and 
from  mouthing  of  articles.  Exposure  also  occurs  from  inhalation  of  air  and 
dust  and  from  dermal  contact  with  articles  and  dust.  The  main  sources  of 
exposure  are  considered  to  be  food,  indoor  environment  and  direct  contact 
with  articles.  According  to  ECHA’s  assessment,  exposure  to  DEHP  in 
women  and  infants  appears  to  be  driven  by  food  consumption,  indoor 
environment and direct contact with articles. 

Emissions to soil and to a lesser extent to the aquatic environment and to air 
occur over long time periods at all stages of the life cycle, mostly at the end-
of-life /waste management stage 

Concerns  for  human 
health  and/or 
the 
environment 

Laboratory  and  epidemiological  evidence  suggesting  risks  of  serious  and 
interlinked  developmental  effects  in  human  males,  and  effects  to  the 
environment 

201 

 
 
 
 
 
 
 
 
Regulatory  hazard 
and risk assessment 

The spectrum of effects caused by suppression of foetal androgen action in 
the  male  rat  is  known  as  the  phthalate  syndrome.  Observed  effects  include 
decreased  gene  expression  related  to  steroid  biosynthesis,  inhibition  of 
testosterone  production,  changes  in  germ  cell  differentiation  leading  to 
effects  on  reproductive  organs  and  fertility  such  as  increased  nipple 
retention,  increased  male  mammary  gland  changes,  decreased  anogenital 
distance,  increased  incidence  of  genital  malformations,  delayed  puberty 
onset, reduced semen quality and testicular changes.  

Evidence from mammalian and aquatic species has also raised concerns over 
potential  risks  for  metabolic  and  immune  systems  and  neurological 
development. 

  1998  The  Scientific  Committee  on  Toxicity,  Ecotoxicity  and  the 
Environment (SCTEE) identifies a risk from the use of DEHP in certain 
toys and childcare articles 

  2001 classified as toxic to reproduction (Cat 1B) 
  2001 listed as a Priority Substance under the Water Framework Directive 

by Decision No 2455/2001/EC 

  2005  EFSA  established  TDI  for  DEHP  (as  well  as  DBP  and  BBP)  and 

subsequent restrictions in plastic FCM. 

  2006  Opinion  of  the  SCCP  on  phthalates  in  cosmetic  products 

SCCP/1016/2006 

  2008 SVHC identification due to reproductive toxicity  
  2008 Environmental risk assessment published by ECB-JRC 
  2008 and 2015 SCHENIHR reviews of 2002 opinion for use in Medical 

Devices 

  2010 – REACH registration 
  2010  ECHA’s  report  on  the  review  of  the  new  available  information 

related to DEHP. 

  2012 ECHA SEAC and RAC opinions on a proposal submitted by DK to 
restrict  DEHP,  DBP,  BBP,  DIBP  based  on  combined  exposure  do  not 
identify a risk for human health  

  2013  Re-designated  as  a  Priority  Hazardous  Substance  under  the  Water 

Framework Directive by Directive 2013/39/EU 
  2014 SVHC identification – ED for environment 
  2017 SVHC identification – ED for human health 
  2017  Based  on  new  data  and  taking  into  account  combined  exposure, 
ECHA SEAC and RAC opinions on a proposal submitted by ECHA with 
the  support  of  DK  ECHA  (on  request  of  the  Commission)  to  restrict 
DEHP, DBP, BBP, DIBP, identifies a risk for human health  

  2017 EC asked EFSA to reassess DBP, BBP, DEHP, DINP and DIDP for 
use  in  FCMs  based  on  new  evidence  on  exposure  and  reproductive 
toxicity  used  by  ECHA  in  the  2015  assessment  based  on  reproductive 
toxicity 

202 

 
 
 
  
Risk  management 
measures 

  2019 EFSA group-based risk assessment of DBP, BBP, DEHP and DINP 
following draft guidance on mixtures: estimated combined exposure and 
established group TDI based on reproductive toxicity 

  2019 SCHEER guidelines for the benefit-risk assessment of the presence 

of CMR/ED phthalates in certain medical devices 

  1999 first restricted in toys and childcare articles made of PVC 
  2003  Restriction  of  the  supply  of  DEHP  as  substance  or  in  mixtures  to 
the  general  public  (Directive  2003/36/EEC  amending  the  Council 
Directive 76/769/EEC) 

  2004  DEHP  included  in  the  list  of  prohibited  substance  in  cosmetics 

(Annex II to the Cosmetic Products Regulation) 

  2005 Ban extended to all toys and childcare articles at >0.1% w/w of the 
plasticised  material  individually  or  in  combination  with  two  other 
phthalates (Directive 2005/84/EC of the EU Parliament and the Council). 
  2007 The restrictions are transposed into the REACH Regulation (Annex 

XVII entry 30 and 51) 

  2007 Authorisations for use in FCMs are laid down (now in Commission 
Regulation (EU)10/201152), together with restrictions on the use of these 
substances, such as specific migration limits 

  2008  Environmental  Quality  Standards  set  for  surface  waters  by 

Directive 2008/105/EC 

  2011  Added 

to  authorisation 

list  (REACH  Annex  XIV).  Latest 
application  date  for  authorisation  21  August  2013  Sunset  date  21 
February 2015.   

  2015  RoHS  restriction  at  >0.1%  by  weight of  homogeneous  material  in 
EEE,  applicable  from  22  July  2019.  Requests  for  time-limited  and 
industry  are  under 
application-specific  exemptions  submitted  by 
consideration. 

  2018  Amendment  of  REACH  Annex  XVII  (entry  51)  by  Commission 
Regulation 2018/2005 restricts DEHP, DBP, BBP and DIBP >0.1% w/w 
(individually  or  in  combination)  in  plasticised  material  with  limited 
exemptions. Restriction takes effect from 7 July 2020. 

  REACH Authorisation: Industry submitted since 2014 in total 6 requests 
for REACH Authorisations. Currently, one of the granted authorisations 
is  still  active.  Other  authorisations  expired,  were  withdrawn,  are  under 
review or a decision is pending. 

  2020  Further  restrictions  under  consideration  for  FCMs  based  on  new 
grouping approach and taking into account exposure from other sources 

152OJ L 12, 15.1.2011, p. 1–89 

203 

 
 
 
 
 
                                                      
2  Substance profile 
Phthalates are a group of chemical substances used for various technical purposes in plastic, rubber 
materials  and  other  polymers.  Their  main  use,  sometimes  up  to  50%  of  plasticised  material,  is  as 
plasticisers  in  normally  hard  plastic  materials  to  make  these  softer  and  more  flexible.  Bis(2-
ethylhexyl) phthalate (abbreviated DEHP) is one of the chemicals belonging to this group. DEHP is 
highly hydrophobic (log Kow = 7.5), poorly soluble although biodegradable in water, soluble in fatty 
and oily matrix. More than 95% of the total use of DEHP has been as an additive in polymers, mainly 
in flexible polyvinyl chloride (PVC)153,154. Plastic material containing DEHP was reported to be used 
in  a  wide  variety  of  articles  for  consumers  as  well  as  for  workers  and  for  professionals,  including 
roofing  material,  cables,  coated  fabrics,  car-under-coatings,  toys,  medical  devices  and  shoe  soles. 
Reported other uses of DEHP included sealants, adhesives, paints, lacquers, printing inks for paper, 
plastics  including  food  processing  equipment,  textiles,  rubber  and  ceramics  for  electronic 
components155. Several of the above mentioned uses of DEHP in articles have been regulated in the 
EU during the last two decades. 

DEHP  has  been  the  most  used  phthalate  plasticiser  to  date  with  an  estimated  tonnage  in  Europe  of 
595,0001  t/y  in  1997,  of  which  78%  were  used  for  indoor  and  22%  for  outdoor  applications  (ECB 
2008).  Since EU  regulatory  action  started  in 1999,  its  use  has  decreased  significantly  as  production 
has gradually shifted to alternative substances including higher molecular weight phthalates  such as 
di-isononyl phthalate (DINP) (ECHA 2017), and declined to below 170.000 t/y in 2014. It is expected 
that the latest amendment of the restriction on phthalates under REACH will lower the tonnages on 
the EU market considerably. 

2.1

  Exposure pathways of concern  

Human Exposure 

According to ECHA, the main sources of human exposure to DEHP are considered to be food, indoor 
environment  (including  occupational  exposure)  and  articles  that  have  a  high  potential  for  direct 
contact.  Whilst  food  was  found  to  be  a  major  source  from  combined  dietary-biomonitoring  studies, 
EFSA has recently estimated that dietary exposure to DEHP and other relevant phthalates that act via 
the  same  mode  of  up  action  contribute  up  to  23%  of  the  temporary  Tolerable  Daily  Intake.  Direct 
exposure from articles can arise from contact between articles and the skin or mucous membrane, or 
from infants mouthing articles. Additionally, medicines and medical devices may contribute through 
oral  intake  and  skin  penetration  to  exposure  of  certain  population  groups.  Furthermore,  exposure 
occurs via slow release of phthalates to the indoor environment  (ingestion of dust and inhalation of 
air)  and  through  migration  from  articles  that  are  used  in  food  processing.  Young  children  may  be 
additionally exposed  via mouthing and dermal contact with toys and other indoor materials (ECHA 
2017). 

153European Chemicals Bureau (2008): EU Risk Assessment Report - bis(2-ethylhexyl) phthalate (DEHP). 
Office for Official Publications of the European Communities, 588 p 
154https://echa.europa.eu/documents/10162/d6e64c7a-8529-bf51-d850-229a8c3abe61 
155DEHP  in  sealants,  adhesives  and  paints  is  restricted  for  professional  and  consumer  uses  under  REACH 
Regulation, Annex XVII, entry #30 

204 

 
 
 
 
                                                      
Environmental Exposure  

Exposure  of  terrestrial  and  aquatic  ecosystems  is  expected  from  emissions  to  soil  and  to  a  lesser 
extent  to  the  aquatic  environment  and  to  air  from  all  stages  of  the  life  cycle.  Most  of  the 
environmental emissions from indoor and outdoor products occur over long time periods at the end-
of-life  /waste  management  stage,  with  significant  emissions  during  products'  lifetime  and  minor 
contributions from the production/processing (ECB 2008).  

2.2

  Hazard endpoints of concern 

Human hazard 

It is believed that the most  vulnerable exposed groups are those associated with critical windows of 
exposure, including pregnant women (due to effects on foetal development). According to the ECHA 
SEAC  and  RAC  2017  opinion,  “there  is  strong  evidence  for  risks  of  serious  and  interlinked 
developmental effects in males, including with high probability reduction of semen quality, testicular 
changes, decreased anogenital distance, decreased foetal testosterone and with moderate likelihood at 
the estimated exposure levels, hypospadias, cryptorchidism and germ cell changes”. Moreover, it has 
been proposed that developmentally impaired germ cells might correspond to precursors of testicular 
germ cell cancer in humans but overall, it is unclear whether exposure to the four phthalates has a role 
in testicular germ cell cancer in humans. In addition, experimental and epidemiological studies have 
suggested  other  possible  effects  not  associated  with  reproductive  toxicity,  including  on  the  immune 
system,  the  metabolic  system  and  neurological  development.  Some  of  these  studies  suggest  that 
reproductive toxicity may not be the most sensitive endpoint. Short-term high exposure level within 
the  critical  windows  of  exposure  may  be  sufficient  to  cause  adverse  reproductive  effects  on  the 
developing foetus. Although the foetus is thought to be more sensitive to the effects of this phthalate, 
children  (boys)  are  also  considered  a  sensitive  population  because  their  reproductive  system  is  still 
developing. 

Environmental Hazard  

Concerning  the  effects  of  DEHP  on  the  environment,  based  on  available  information  from 
mammalian and ecotoxicological studies (ECHA 2014), adverse effects concerning development and 
reproduction  are  generally  regarded  as  endpoints  of  particular  relevance  because  such  effects  are 
likely  to  manifest  themselves  at  the  population  level.  The  effects  observed  in  rats  are  of  particular 
concern for mammalian wildlife species with a natural low reproductive output (including endangered 
species)  as  negative  effects  on  reproduction  have  an  even  higher  potential  for  causing  long  term 
negative  effects  at  the  population  level  for  such  taxa.  Exposure  to  DEHP  is  reported  to  affect 
steroidogenesis (e.g., decreased foetal testosterone production) resulting in adverse effects in the male 
reproductive  system  (e.g.,  effects  on  sex  ratio,  ovo-testis)  in  a  range  of  mammalian  and  non-
mammalian  wildlife  across  taxonomic  groups  representative  of  both  terrestrial  and  aquatic 
ecosystems. Several studies in fish indicate that DEHP has an estrogenic mode of action which may 
cause the sex reversal of male fish to female fish and / or affect reproductive output. DEHP appears to 
act  via  relatively  weak  anti-androgenic  or  oestrogenic  mechanisms.  However,  effects  that  could  be 
mediated  by  the  thyroid  axis  have  also  been  noted  by  some  authors  for  some  species  of  fish  and 
amphibians.  Recent  evidence  from  mammalian  and  aquatic  species  has  also  raised  concerns  over 
potential risks for metabolic and immune systems and neurological development. 

205 

 
 
 
 
Figure 17.1. DEHP case study: illustration of applied provisions across legislation156 

156CLP: Classification, Labelling and Packaging regulation (including pre-CLP legislation (67/548/EEC, and 1999/45/EC); REACH: Registration, Evaluation and 
Authorisation and restriction of Chemical substances (including pre-REACH legislation (EEC) No 793/93); GPSD: General Product Safety Directive; TSD: Toy Safety 
Directive; MDR: Medical Devices Regulation; RoHS: Restriction of Hazardous Substances in electric and electronic devices; FCM: Food Contact Material Regulation; 
Waste: Waste Framework Directive; Water: Water Framework Directive and Environmental Quality Standards Directive. 

206 

 
 
 
                                                      
207 

 
 
 
3  DEHP and other phthalates in EU legislation 

  Regulating phthalates under REACH and preceding legislation 

3.1
In the 1990s, concerns grew that exposure to DEHP poses a risk especially for infants, while scientific 
reviews  generally  concluded  that  there  should  be  no  concerns  for  the  vast  majority  of  adults  in 
relation  to  toxicity  following  DEHP  exposure157,  158.  The  Scientific  Committee  on  Toxicity, 
Ecotoxicity  and  the  Environment  (CSTEE),  mandated  by  the  Commission  to  estimate  the  risk  for 
children, suggested in 1998 the need to limit the concentration of DEHP in plastics used for toys and 
childcare articles based on toxic effects on the liver (hepatic peroxisome proliferation). Furthermore, 
according  to  the  opinion  of  the  CSTEE,  laboratory  tests  with  rodents  showed  adverse  effects  on 
kidneys  and  testicular  damage.  In  2001,  DEHP  was  classified  at  the  EU  level159  as  being  toxic  to 
reproduction category 1B due to effects on fertility and the reproductive system. Already in 1999, the 
Commission  restricted160  under  the  General  product  Safety  Directive161  the  use  of  PVC  containing 
phthalates in certain toys and childcare articles for young children made of soft PVC. This restriction, 
which  was  based  on  a  scientific  assessment  carried  out  by  a  scientific  committee  tasked  by  the 
Commission162, was then extended and made permanent in 2005 (Directive 2005/84/EC) in order to 
cover all toys and childcare articles made of plasticised material. The restriction was later taken over 
into REACH, after this Regulation entered into force in June 2007.  

In 2011, DK proposed to restrict four phthalates (DEHP, DBP, BBP, DIBP) based on their combined 
exposure. However, the Risk Assessment Committee (RAC) at ECHA concluded that data available 
could not demonstrate a risk from either of the phthalates or from their combined exposure.  

Besides  restrictions,  REACH  foresees  the  authorisation  procedure  to  assess  and  control  the  risks  of 
substances with certain hazardous properties, called Substances of Very High Concern (SVHCs) that 
are  listed  in  Annex  XIV  of  REACH.  This  regulatory  measure  puts  the  obligation  on  industry  to 
demonstrate  that  the  risk  from  the  use  of  a  chemical  substance  is  adequately  controlled  or  benefits 
from the use outweigh the risks and there are no alternative substances or technologies. Only in these 
cases  industry  can  receive  an  authorisation  to  use  a  substance.  However,  authorisations  cannot  be 
obtained  for  uses  that  are  already  restricted.  Authorisations  are  granted  by  the  Commission  and 
require  periodical  reviews.  Industry  is  obliged  to  analyse  alternatives  to  the  use  of  a  hazardous 
substance for which they apply. It is worth to note that the authorisation requirement does not concern 
imported articles. 

The first step of the authorisation procedure is the identification of a substance as SVHC. Identified 
substances  are  listed  on  the  REACH  Candidate  List.  Reasons  for  identification  can  be  that  the 
substance meets the criteria for the classification as carcinogenic, mutagenic or toxic to reproduction 
category 1A or 1B (CMR Cat. 1A/1B), or that the substance is persistent, bioaccumulative and toxic 

157SCMPMD/2002/0010 
158Alternative analysis provided in: http://www.durodie.net/pdf/PoisonousDummies.pdf/  
159EC (2001): Commission Directive 2001/59/EC of 6 August 2001 adapting to technical progress for the 28th 
time Council Directive 67/548/EEC on the approximation of the laws, regulations and administrative provisions 
relating to the classification, packaging and labelling of dangerous substances. O.J. L225. 21.8.2001, p.1 – 333.  
160Decision 1999/815/EC 
161Council Directive 92/59/EEC 
162Scientific Committee on Toxicity, Ecotoxicity and the Environment (SCTEE) 

208 

 
 
 
                                                      
(PBT), or very persistent and very bioaccumulative (vPvB), and thus hazardous to the environment163 
or a substance has properties that are of an equivalent level of concern to those of the substances of 
the previous categories. Endocrine disrupting properties with probable serious effects to humans or to 
the  environment  qualify  a  substance  as  being  of  very  high  concern,  if  the  effects  give  rise  to  an 
equivalent level of concern to CMRs Cat. 1A/1B or to PBT/vPvBs.  

With the scientific information growing over the years, DEHP was identified as an SVHC for three 
reasons. In 2008, its toxicity to reproduction, for which DEHP was also classified in 2001, led to its 
SVHC  identification  in  2008  and  inclusion  in  the  candidate  list.  The  latter  triggers  the  following 
obligations: 

  Producers  or  importers  of  articles  must  notify  ECHA  if  their  article  contains  DEHP,  if  it  is 
present  in  the  article  above  0,1%  and  the  quantity  of  DEHP  in  the  imported  or  produced 
article is above 1 tonne per year (REACH Article 7(2)) 

  Suppliers  of  DEHP,  or  of  mixtures  containing  the  substance,  must  provide  their  customers 

with a Safety Data Sheet (REACH Article 31(1) and Article 31(2)). 

  Suppliers  of  articles  must  inform  downstream  users,  and  on  request  consumers,  if  the 

substance is present in an article at a concentration > 0.1 % (REACH Article 33) 

The same effects, since caused by an endocrine mode of action, resulted in an additional identification 
in  2017  as  SVHC  of  an  equivalent  level  of  concern  due  to  its  endocrine  disrupting  properties  to 
human  health.  Three  years  earlier,  in  2014,  DEHP’s  endocrine  disrupting  properties  to  the 
environment  were  added  to  the  existing  SVHC  listing.  The  additional  inclusion  of  ED  effects  to 
human health and the environment in the SVHC list triggered provisions for risk assessment of these 
properties (Chemical Safety Report) and risk communication (Safety Data Sheets). Furthermore, those 
properties require specific consideration of ED effects in reviews of authorisation. 

In  2011  the  Commission  included  DEHP  in  the  authorisation  list  (Annex  XIV  of  REACH) 
(Commission regulation (EU) No 143/2011) due to its reproductive toxicity. This inclusion set up the 
obligation for industry to apply for authorisation by 21 August 2013 (latest application date) for the 
uses  of  DEHP  it  wanted  to  continue  after  21  February  2015  (sunset  date).  After  this  date  uses  of 
DEHP  were  not  allowed  any  more  unless  an  authorisation  was  granted  or  an  application  for 
authorisation  had  been  submitted  to  the  Europeans  Chemicals  Agency  (ECHA)  by  the  latest 
application  date.  An  update  of  Annex  XIV  of  REACH  is  currently  in  preparation  with  the  view  of 
updating  its  SVHC  properties  of  DEHP  to  also  list  its  endocrine  disrupting  properties  for  human 
health  and  for  the  environment.  Listing  of  DEHP  due  to  its  endocrine  disrupting  properties  for  the 
environment  will  make  authorisation procedures  applicable  also  to  uses  regulated  by  sector-specific 
regulations  (e.g.  food  contact  materials,  medical  devices)  as  regards  environmental  risks. 
Authorisation is also required for DEHP contained in recycled PVC.  

Up to November 2019, three applications for authorisation have been granted by the Commission in 
consultation  with  Member  States  and  after  an  in-depth  assessment  by  the  responsible  scientific 
committees  at  ECHA164:  in  2014  for  seven  years  for  a  use  in  the  production  of  aircraft  engines,  in 
2015  for  four  years  for  a  military  use  (authorisation  expired)  and,  in  2016,  for  four  years  to  three 
companies for two uses of recycled soft PVC containing DEHP to produce PVC blends and certain 
PVC  articles.  In  the  meantime,  this  authorisation  has  expired  in  2019  for  two  out  of  three 

163REACH Art. 57 
164https://ec.europa.eu/docsroom/documents/37301 

209 

 
 
                                                      
authorisation  holders.  Two  authorisation  holders  have  submitted  a  review  report  requesting  to 
continue this use. Due to regulatory pressure for phasing out this substance, one company withdrew 
their  submitted  review  report  and  only  one  company  is  applying  for  a  review.  The  Commission 
decision  on  the  review  of  authorisation  for  the  latter  holder  is  currently  pending.  The  Commission 
decision is also pending on one another application on uses of DEHP in PVC. 

One  example  of  an  authorisation  is  that  granted  to  the  company  Rolls-Royce  plc  for  a  use  in  the 
manufacturing of fan blades for aircraft engines. At the time of applying for authorisation, technically 
feasible alternatives for the use of DEHP were not available. The risks arising from using DEHP when 
producing the fan blades are adequately controlled, and the substance is ultimately destroyed by the 
very high temperature fan blade forming process. Rolls Royce was authorised  to use DEHP for this 
purpose, with a review date in 2022.  

Authorisation under REACH does not affect the import of articles containing a SVHC into the EU. 
REACH  however  foresees  an  obligation  for  ECHA  to  assess  whether  further  restrictions  should  be 
introduced  after  the  sunset  date,  if  there  is  a  risk  from  use  of  Annex  XIV  substances  in  articles, 
including  those  imported.  Accordingly,  a  restriction  dossier  on  DEHP  and  3  other  phthalates165  in 
articles was initiated.  Based on the opinions from the scientific committees at ECHA responsible for 
assessing  the  risk  and  the  socioeconomic  impacts166  (ECHA  2017),  the  Commission  has  adopted  a 
restriction  by  Regulation  (EU)  2018/2005  amending  Annex  XVII  to  REACH.  The  risk  assessment 
considered  derived  no-effect  levels  for  toxicity  to  reproduction  that  were  based  on  N(L)OAELs  for 
anti-androgenic  effects  seen  in  developmental  studies.  A  NOAEL  for  DEHP  based  on  testicular 
effects (germ cell depletion, reduced testis weight) in male offspring in Wolfe and Layton (2003) was 
selected for the combined risk assessment. RAC and SEAC considered that DEHP and the other three 
phthalates  have  the  same  mode  of  action  and  based  the  risk  assessment  on  combined  exposure  and 
effects of the substances. The exposure assessment considered recent biomonitoring data from the EU 
funded  DEMOCOPHES  programme.  Consequently,  DEHP  and  the  other  three  phthalates  are  not 
permitted to be placed on the market after 7 July 2020 in articles, individually or in any combination 
in a concentration equal to  or greater than 0,1 % by weight of the plasticised  material in the article 
Only few exemptions were introduced in the restriction, namely “for industrial or agricultural use, or 
for  use  exclusively  in  the  open  air,  provided  that  no  plasticised  material  comes  into  contact  with 
human  mucous  membranes  or  into  prolonged  contact  with  human  skin”  and  for  other  specific  uses 
critical to safety (aircraft, motor vehicles). The restriction also updates the conditions for the ban in 
toys  and  childcare  articles  and  extends  it  to  DIBP,  setting  a  limit  of  0.1%  w/w  on  the  total 
concentration  of  the  four  phthalates  in  plasticised  materials.  It  is  expected  that  this  restriction  will 
considerably lower the quantify of phthalates in articles placed on the EU market. 

  Enforcement of regulatory measures under REACH 

3.2
The  Member  States,  ECHA  and  the  Commission  all  play  a  role  in  enforcement  of  REACH.  The 
Member  States  have  the  legal  powers  to  enforce  against  duty  holders.  However,  REACH  also 
stipulates some roles related to enforcement to ECHA with the creation of the Forum for Exchange of 
Information on Enforcement (the Forum)167 which is a network of national authorities responsible for 

165Benzyl butyl phthalate (BBP), Dibutyl phthalate (DBP) and Diisobutyl phthalate (DIBP) 
166The Risk Assessment Committee (RAC) and the Committee for Socio-economic Analysis (SEAC) 
167REACH Art 76(1)(f) 

210 

 
 
 
                                                      
the enforcement of the REACH as well as the CLP168, Biocidal Products and PIC169 Regulation. The 
Commission's  role  is  to  guide  on  policy  issues,  provide  clarity  on  the  implementation  of  REACH, 
facilitating enforcement by Member States.  

The Forum coordinates various enforcement projects, which are designed to harmonise enforcement 
in  Member  States  and  check  the  current  level  of  compliance  regarding  obligations  imposed  on 
industry by REACH, CLP, Biocidal Products and PIC Regulation. The REF-projects170 are carried out 
by  inspectors  based  in  the  national  authorities  in  the  participating  Member  States.  The  resulting 
information is collected by ECHA and the Forum Working Group. Findings of the REF projects are 
them summarised in a final report. Ultimately, the goal of the REF-projects is to improve the quality 
of  enforcement  in  the  Member  States  but  also  to  improve  the  compliance  of  duty  holders  with 
REACH and other legislations.  

In  2016,  the  Forum  launched  an  enforcement  project  to  control  the  compliance  with  the  REACH 
restriction on phthalates in toys and childcare articles171,172. The project consisted mainly of chemical 
analysis  of  the  restricted  phthalates  in  articles.  Toys  and  childcare  articles  were  purchased  by 
authorities in local shops or via the internet. As normal for enforcement checks, articles were selected 
by authorities based on their experience on which types of articles are likely to be non-compliant. The 
selection is hence not representative for the whole toys and childcare market. 

In total, 464 toy products were checked for the phthalates DEHP, BBP and DBP in the project. 19.7 % 
of  the  inspected  toys  contained  one  of  the  phthalates  above  the  permitted  level.  Of  193  childcare 
articles,  7  articles  (i.e.  3,6%)  were  non-compliant.  Most  products  checked  during  the  enforcement 
project (including other products than toys or childcare articles) and found to be non-compliant come 
from countries outside of the European Economic Area or are of unknown origin. 

The report on the enforcement project concluded that the rate of non-compliance for phthalates in the 
selected toy articles is rather high and that the findings are a special point of concern considering that 
those articles are intended to be used by children. 

Member  States  have  also  been  controlling  FCMs  for  phthalates  including  DEHP  in  response  to 
Commission  Recommendation  (EU)  2019/  794173.  The  findings  so  far  indicate  that,  for  the  vast 
majority of samples analysed, DEHP is not present or is not migrating into food.  

  Regulating phthalates under food contact materials (FCM) 

3.3
Phthalates  may  be  present  in  several  food  contact  articles,  primarily  in  plastic  FCMs  for  increasing 
flexibility  of  PVC  or  other  polymers  as  well  as  rubber.  Phthalates  may  migrate  into  food  from 
processing equipment, such as tubes used in the beverage industries, conveyor belts and vinyl gloves 
used in the preparation of foods. They may also be present in some types of packaging such as in the 
seals between a glass jar and its metal lid although recent information collected by the Commission 

168Classification, Labelling and Packaging (CLP) Regulation ((EC) No 1272/2008) 
169The Prior Informed Consent Regulation (PIC, Regulation (EU) 649/2012) administers the import and export 
of certain hazardous chemicals and places obligations on companies who wish to export these chemicals to non-
EU countries 
170REACH-EN-FORCE (REF) projects 
171REACH Annex XVII entry 51 restricting DEHP, BBP and DBP in toys and childcare articles 
172ECHA (2018): Forum REF-4 Project Report - Harmonised Enforcement Project on Restrictions. ECHA 
Report ECHA-18-R-03-EN, Helsinki (https://echa.europa.eu/fr/-/inspectors-find-phthalates-in-toys-and-
asbestos-in-second-hand-products) 
173http://data.europa.eu/eli/reco/2019/794/oj  

211 

 
 
                                                      
indicates that these have largely been replaced in the EU by non-phthalate plasticisers174. In order to 
be used in FCM plastics,  phthalates  must be assessed and authorised according  to FCM  legislation, 
including an assessment by the European Food Safety Authority (EFSA). 

There are five phthalates listed and authorised as additives in the positive list in Annex I (Table 1.1) 
of  Regulation  (EC)  No  10/2011:  (di-butylphthalate  (DBP,  FCM  No  157),  butyl-benzyl-phthalate 
(BBP, FCM No 159), Bis(2-ethylhexyl)phthalate (DEHP, FCM No 283), di-isononylphthalate (DINP, 
FCM No 728), and di-isodecylphthalate (DIDP, FCM No 729). 

In  2005,  EFSA  published  opinions  on  five  phthalate  esters,  DBP,  BBP,  DEHP,  DINP  and  DIDP, 
considering updated toxicological information at that time, relevant to reproductive toxicity. Based on 
these  opinions,  these  five  phthalates  are  currently  authorised  for  use  as  plasticisers  and  technical 
support agents in plastic FCMs. The authorisations are laid down in Commission Regulation (EU) No 
10/2011175, together with restrictions on the use of these substances, such as specific migration limits 
(SMLs),  taking  into  account  exposure  from  other  sources  where  necessary,  as  well  as  additional 
restrictions on their use.  

On 1 April 2016, ECHA, in cooperation with Denmark, prepared an Annex XV dossier for the four 
phthalates DBP, BBP, DEHP and DIBP and on 29 August 2017, the Agency submitted the opinions 
of RAC and SEAC to the Commission. Based on those opinions, the Commission adopted restriction 
of the four phthalates in articles (Regulation (EU) 2018/2005). Food contact materials are exempted 
from the restriction, except from childcare articles intended to facilitate the feeding of children, which 
are covered by the REACH restriction. 

In light of the ECHA RAC opinion based on new biomonitoring information which became available 
only after EFSA’s 2005 opinion, the Commission asked EFSA in July 2017 to re-assess the safety of 
the five authorised phthalates used in plastic FCMs, taking into account in particular new information 
on reproductive toxicity used in the development of the restriction dossier as well as data examined in 
a classification proposal for DINP.  

Based on its assessment176, EFSA has set a new safe level – a group Tolerable Daily Intake (TDI) – 
for four of the five phthalates (DBP, BBP, DEHP and DINP) of 50 micrograms per kilogram of body 
weight (µg/kg bw) per day based on their effects on the reproductive system. The key effect on which 
this  group-TDI  is  based  is  a  reduction  in  testosterone  in  foetuses.  The  fifth  phthalate  in  the 
assessment,  DIDP,  does  not  affect  testosterone  levels  in  foetuses,  therefore  a  separate  TDI  of  150 
µg/kg bw per day has been set based on its effects on the liver (as per the 2005 evaluation). The new 
assessment of the five phthalates is in line with the 2005 assessment in terms of their most sensitive 
effects and the individual tolerable daily intakes. 

EFSA improved its estimate of dietary exposure to phthalates and concluded that current exposure to 
these five phthalates from  food is not a concern for public health. Dietary exposure to the group of 
DBP,  BBP,  DEHP  and  DINP  for  average  consumers  is  7  µg/kg bw  or  seven  times  below  the  safe 
level, while for high consumers it is 12 µg/kg bw, which is four times lower. For DIDP, the dietary 
exposure for high consumers is 1,500 times below the safe level. However, EFSA has set all the TDIs 
on a temporary basis due to uncertainties about effects other than the reproductive ones and about the 

174https://ec.europa.eu/food/sites/food/files/safety/docs/cs_fcm_wg_20200224_pres-02.pdf 
175http://data.europa.eu/eli/reg/2011/10/2019-08-29 
176EFSA Journal 2019;17(12):5838 

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contribution of plastic FCMs to overall consumer exposure of phthalates. EFSA identified a need to 
address these uncertainties by considering the whole body of evidence.  

The Commission is currently assessing EFSA’s Opinion and the adequacy of existing EU measures 
and  considering  what  if  any  changes  or  additional  measures  are  necessary  at  EU  level177.  In 
recognition  of  the  limitations  and  uncertainties  identified  in  the  EFSA  opinion  and  to  address  its 
recommendations,  the  Commission  is  also  mandating  EFSA  to  carry  out  a  full  re-assessment  of 
phthalates  in  FCMs,  taking  into  account  all  available  information  to  ensure  the  highest  level  of 
protection for consumers. 

  Regulating DEHP in cosmetics 

3.4
The use of DEHP in cosmetic products is prohibited as it was classified as toxic for reproduction (Cat 
1B)  under  the  Council  Directive  67/548/EEC  in  2001.  The  ban  came  into  force  in  December  2004 
(currently under entry 677 of Annex II to the Cosmetic Products Regulation).  

A  Greenpeace  investigation  published  in  February  2005  examined  inter  alia  the  presence  of  10 
phthalates  in  perfumes  (Greenpeace  2005).  It  should  be  noted  that  the  Greenpeace  sampling  was 
carried  out  on  products  prior  to  the  effective  date  of  the  ban  of  certain  phthalates  in  cosmetics  (i.e. 
between 2003 and 2004, before DEHP was banned in cosmetic products). In this investigation, DEHP 
was found in some perfumes, usually in low concentrations. The Commission mandated the Scientific 
Committee on Consumer Products (SCCP  1016/2006) to carry out inter alia a risk assessment using 
the highest reported concentration of 167 mg/kg of DEHP in perfumes samples. The SCCS concluded 
‘the inadvertent occurrence of DEHP at trace levels in cosmetics does not seem to be a concern for 
consumer  health  and  ‘in  view  of  the  low  concentrations  [of  phthalates]  found  in  the  samples  of 
perfume analysed, there would be no quantifiable risk for the consumer’.”  

  Regulating DEHP in medical devices 

3.5
Medical devices made of PVC, such as blood bags, catheters, and endotracheal tubing, almost always 
contain DEHP, where its function is to make the material more flexible and durable. Risks associated 
with  DEHP  leaching  potential  have  raised  concerns  among  some  Member  State  authorities, 
particularly for neonates in intensive care units, in view of the relatively high exposure per unit body 
mass.  In  2002,  the  Commission  mandated  the  Scientific  Committee  on  Medicinal  Products  and 
Medical  Devices  to  produce  an  opinion  on  “Medical  Devices  containing  DEHP  plasticised  PVC; 
Neonates and Other Groups Possibly at Risk from DEHP toxicity”178.  The Committee concluded that 
“there is no evidence that any of these groups do experience DEHP related adverse effects”. However, 
the Committee also stated that “a lack of evidence of causation between DEHP-PVC and any disease 
or adverse effect does not mean that there are no risks”. To take account of new information on the 
safety  of  DEHP,  the  Commission  mandated  the  Scientific  Committee  on  Emerging  and  Newly 
Identified  Health  Risks  (SCENIHR)  to  carry  out  two  reviews  of  this  opinion,  in  2008179  and  in 
2015180,  which  also  included  an  assessment  of  possible  alternative  substances.  The  Committee 
restated concerns due to the short-term but high exposure of neonates in intensive care, as well as for 

177https://ec.europa.eu/food/sites/food/files/safety/docs/cs_fcm_wg_20200224_pres-01.pdf 
178SCMPMD/2002/0010 
179SCENIHR/2008/014 
180SCENIHR/2015/047 

213 

 
 
 
 
                                                      
adult haemodialysis patients, although the currently available data is still inconclusive or inconsistent. 
The  available  data  on  toxicology,  leaching  and  functional  efficacy  of  alternatives  was  also 
insufficient. The Committee formulated specific needs for research that would help provide adequate 
risk assessment for vulnerable groups of patients and inform judgement of the suitability of alternative 
plasticisers. 

In conclusion, although concerns for the use of DEHP-PVC in vulnerable patients cannot be ruled out, 
bearing  in  mind  that  many  interventions  in  question  are  life-saving,  the  benefit-risk  ratio  generally 
remains favourable for the use of such devices, where no alternatives are available.  

Under  the  new  Regulation  on  Medical  Devices,  manufacturers  will  be  obliged  to  re-evaluate  the 
presence  of  DEHP  (classified  as  toxic  for  reproduction  category  1B  and  identified  as  SVHC  for 
endocrine  disrupting  properties  to  human  health  and  to  the  environment  under  REACH)  in  their 
devices  at  levels  above  0,1%  weight  by  weight,  providing  reasoning  why  it  is  indispensable  at  the 
concentration  used  and  taking  into  account  guidelines  for  the  benefit-risk  assessment  of  phthalates 
recently  prepared  by  the  Scientific  Committee  on  Health,  Environmental  and  Emerging  Risks 
(SCHEER  2019181).  The  forthcoming  listing  DEHP  as  SVHC  due  to  its  endocrine  disrupting 
properties to the environment will make uses of the substance in medical devices subject to REACH 
authorisation,  requiring  the  applicant  to  demonstrate  that  the  benefits  from  the  use  outweigh  the 
environmental risks and that there are no alternatives.  

In  2015,  DEHP  was  included  in  Annex  II  of  RoHS  based  on  concerns  regarding  EEE  waste 
management  implications182.  The  restriction  took  effect  in  July  2019.  Therefore,  medical  devices 
covered by the RoHS Directive should follow the specific provisions under RoHS.  

  Regulating DEHP at the interface of chemical and waste legislation 

3.6
The  presence  of  hazardous  substances,  such  as  DEHP,  in  materials  and  products  not  only  concerns 
chemical  and  product  safety  legislation.  It  also  has  profound  implications  for  waste  legislation.  As 
society  moves  towards  a  circular  economy,  there  are  two  boundaries  between  the  chemical  and  the 
waste legislation: the end-of-life on one side and the end-of-waste on the other. The first boundary is 
crossed  when  products  reach  the  end-of-life  stage  and  become  waste;  the  second  when  waste  is 
recycled  into  secondary  materials  and  products.  As  long  as  hazardous  substances  are  part  of  waste, 
they are regulated under the Waste Framework Directive and related policy instruments.  

From the point of view of waste legislation, the potential negative impacts of hazardous substances in 
material cycles can be controlled by restrictions in products, waste management rules (e.g. treatment 
requirements,  traceability of  waste  streams)  and  provisions  for  end-of-waste  criteria.  Restrictions  in 
products belong to the chemical and product specific domain (e.g. REACH, RoHS). In 2015, DEHP 
was  included  in  Annex  II  of  RoHS  based  on  concerns  regarding  EEE  waste  management 
implications182. The restriction took effect on 22 July 2019. With the increasing regulatory actions on 
DEHP  since  1999  up  to  the  recent  regulatory  measures  (e.g.  obligation  to  obtain  an  authorisation 
under REACH, REACH restriction on plasticised  material (applicable from 8 July 2020 on), listing 
under RoHS), the presence of DEHP in products and recycled materials decreased and will be further 
minimised. However, its presence in materials and products becoming waste has proved problematic. 

181https://ec.europa.eu/health/sites/health/files/scientific_committees/scheer/docs/scheer_o_015.pdf  
182https://ec.europa.eu/transparency/regdoc/rep/3/2015/EN/3-2015-2067-EN-F1-1.PDF 

214 

 
 
 
                                                      
As  a  category  1B  reproductive  toxicant  under  the  CLP  regulation,  any  material  containing  DEHP 
above 0.1% is classified as "hazardous" under the waste directive (2008/98/EC). As such it is subject 
to  specific  provisions  including  the  need  to  decontaminate  material  flows  to  ensure  safety. 
Technically, treatment of PVC waste to reduce DEHP below 0.1% is expensive and energy intensive 
and therefore not considered feasible. The quality of recycled materials can be controlled by setting 
end-of-waste  criteria  under  waste  legislation.  However,  although  end-of-waste  criteria  for  plastics 
were proposed by the JRC in 2012 (JRC 2012), unresolved debate among stakeholders meant that no 
agreement at the EU level was reached. The lack of agreed EU-wide end-of-waste criteria for plastics 
constitutes an important regulatory gap for waste operators. It leaves room for different interpretations 
by  operators  in  the  waste  recycling  industry  and  in  national  authorities.  The  debate  remains 
unresolved  to  date.  As  a  result  of  the  claim  that  DEHP  is  less  bioavailable  in  recycled  PVC,  some 
industries  have  assumed  that  DEHP-containing  recycled  PVC  meets  the  generic  end-of-waste 
conditions  laid  out  in  Article  6  of  Directive  2008/98/EC  on  waste,  thus  crossing  into  the  chemical 
regulatory  domain.  Directive  2008/98/EC  as  an  EU  Directive  is  however  not  directly  applicable  to 
economic operators. Currently, since no end-of waste criteria have been established at EU or Member 
State  level,  national  authorities  are  to  take  end-of-waste  decisions  as  and  if  appropriate.  So  far,  no 
such cases have been notified to the Commission. On this side of the legislative interface, the use of 
recycled materials that have stopped being waste and that contain substances listed in REACH Annex 
XIV  is  subject  to  authorisation.  This  applies  to  DEHP  as  well  as  to  any  other  plastic  additives 
included in REACH Annex XIV. 

The case of DEHP in recycled PVC illustrates the current situation, as analysed in detail in the "Study 
for  the  strategy  for  a  non-toxic  environment  of  the  7th  EAP"  (EC  DG  ENV  2017).  In  2013,  three 
companies submitted an authorisation application for the use of recycled soft PVC containing DEHP 
in formulations and in industrial processes to produce certain PVC articles. ECHA’s RAC concluded 
that the risk from those uses is not adequately controlled, while its SEAC concluded that the benefits 
from  the formulation of  recycled PVC containing DEHP and from its use to produce certain PVC 
articles outweigh the risk and that there are no suitable alternatives. In view of the RAC and SEAC 
opinions, in 2016 the EU Commission granted the authorisation based on risk-benefit considerations, 
with a review period of four years, on the condition that the DEHP content in recycled PVC does not 
exceed  20  %  (w/w).  The  authorisation  is  only  applicable  provided  that  the  recycled  PVC  material 
containing  DEHP  has  ceased  to  be  waste.  If  this  is  not  the  case,  the  waste  legislation  applies  for 
handling and processing of this material. The granted authorisation does not cover toys and childcare 
articles; erasers; adult toys (sex toys and other articles for adults with intensive contact with mucous 
membranes;  household  articles  smaller  than  10  cm  that  children  can  suck  or  chew  on;  consumer 
textiles/clothing  intended  to  be  worn  against  the  bare  skin,  cosmetics  and  food  contact  materials 
(C(2016)3549). The need to reassess the availability of alternatives and the fact that in the application 
adequate  control  of  risks  to  workers  during  formulation  and  article  production  could  not  be 
demonstrated  justified  the  review  period  of  the  authorisation.  Due  to  regulatory  pressure  for 
substituting  this  substance  with  alternatives  and  phasing  it  out,  only  one  of  the  three  companies  is 
pursuing  a  review  of  this authorisation in  2017.  A  Commission  decision  on  this  review  is  currently 
pending.  

  Regulating DEHP under the Water Framework Directive 

3.7
DEHP  has  been  listed  as  a  priority  substance  under  the  Water  Framework  Directive  (WFD)  since 
2001.  Its  inclusion  in  the  priority  list  was  motivated  by  a  relatively  high  modelling-based  ranking 

215 

 
 
(#14)  combined  with  additional  evidence  of  environmental  occurrence  and  endocrine  disrupting 
effects183.  In  2008  an  Environmental  Quality  Standard  (EQS)  was  set  of  1.3  µg/l  in  surface  waters 
(Directive  2008/105/EC). Its  identification  as  a  Substance  of  Very  High  Concern  under  REACH  in 
2008  motivated  a  proposal  to  change  the  status  of  DEHP  from  a  Priority  Substance  to  a  Priority 
Hazardous Substance. An impact assessment followed, which analysed the costs and benefits of the 
modified  regulatory  status  (ENTEC  2011).  Annex  X  to  the  WFD  as  amended  by  Directive 
2013/39/EU  thus  designates  DEHP  as  a  Priority  Hazardous  Substance.  In  accordance  with  WFD 
Article 16(6) all emissions of DEHP to the aquatic environment should be phased out within 20 years. 

4  Impact of regulation 

4.1

  Decline in use and exposure  

Since the initial regulatory action in 1999 and with the increasing restrictions coming into force over 
the following years, DEHP production and use in the EU has declined. Between 2005 and 2013, the 
estimated combined production of DEHP, DBP and DIBP in the EU28 declined from about 409,000 t 
to 90,000 (ECHA 2017b). At present, only one company is still manufacturing DEHP, for which an 
application  for  authorisation  for  two  uses  of  this  substance  is  pending.  Placing  on  the  market  of 
articles, i.e. manufacturing in the EU as well as import of articles, containing four phthalates (DEHP, 
DBP,  DiBP,  BBP)  were  estimated  to  equal  179,000  t/y  in  2011.  It  is  expected  that  with  the  latest 
amendment  of  the  restriction  on  phthalates  (DEHP,  DBP,  DiBP,  BBP)  under  REACH  imports  of 
articles  containing  those  phthalates  will  be  reduced  considerably  to  well  below  10.000  t/y  (ECHA 
2017b). 

Recent studies have reported declining historical trends in urinary concentrations of most phthalates 
and  their  metabolites.  Biomonitoring  data  from  the  EU  project  DE  MO  COPHES  was  used  to 
demonstrate  a  decline  in  human  exposure  to  phthalates  in  the  background  document  supporting  the 
opinions on the REACH restriction proposal (ECHA 2017). Between 2001 and 2011 exposure to the 
four restricted phthalates including DEHP has decreased by between 30% and 80% depending on the 
study  location  and  design.  Long-term  24h-urine  monitoring  from  the  German  Eenvironmental 
Specimen  Bank  (ESB)  reveal  a  roughly  10-fold  decline  in  internal  exposure  levels  of  DEHP 
metabolites from their peak levels in the late 1980s/early 1990s compared to most recent levels from 
2015  (Göen  et  al  2011,  Koch  et  al  2016).  The  same  study  also  reports  constant  or  even  slightly 
declining  levels  of  di-isononyl  phthalate  (DINP),  one  of  the  main  replacements  for  DEHP.  The 
authors  suggested  that  probably,  non-phthalate  alternatives  are  increasingly  taking  over  from  the 
phthalates in Germany. A comparison with the American NHANES data indicates that this is not the 
case in the US, where high-molecular-weight phthalates, such as DINP, seem be gaining importance. 
Overall, internal exposure to most phthalate metabolites monitored in both countries, including those 
from  DEHP,  seems  to  be  lower  in  Germany  than  in  the  US.  Studies  from  other  EU  countries  have 
consistently reported declining trends in DEHP urinary metabolites. The sum of the concentrations of 
DEHP metabolites from samples collected from populations in central Italy showed on average a 4-
fold reduction between 2011 and 2016 (Tranfo et al 2018); a 3-fold reduction was observed between 

183https://ec.europa.eu/environment/water/water-dangersub/pdf/commps_report.pdf 

216 

 
 
 
 
                                                      
the 2007-2011 FLEHS II and 2012-2015 FLEHS III monitoring campaigns in Flanders (Schöeters et 
al 2017).  

  Shift to alternatives 

4.2
The decrease in production volumes in recent years reflects the fact that DEHP for many applications 
has  been  replaced  by  alternative  solutions,  including  higher  molecular  weight  phthalates,  non-
phthalate plasticisers and alternative materials.   

The  main  alternative  plasticisers  in  PVC  have  been  DINP  and  di-isodecyl  phthalate  (DIDP). 
According to a study commissioned by ECHA in 2008, DINP and DIDP have dominated in marketed 
PVC flooring, wall coating and carpets with PVC backcoating after 2000 and the publication date of 
the study (COWI 2009). However, despite the continuous decline in DEHP exposure since the 1990s, 
no significant increase has been observed in those two substitutes (Koch et al 2016), suggesting that 
DEHP has not been substituted only by high- molecular-weight phthalates but also by non-phthalate 
plasticisers and alternative materials. In fact, non-phthalate alternatives have replaced DEHP in uses 
that raised the biggest concerns as regards human exposure: toys, medical products, food packaging 
and water beds (COWI 2009). It is likely that the reduction in environmental emissions and exposure 
from other product types could be significantly slower. Similarly, to other  toxic additives in articles 
and  materials,  DEHP  may  remain  in  the  materials  cycle  for  decades,  even  if  measures  are  taken  to 
prevent the use of those articles/materials or to decontaminate waste streams (Pivnenko et al. 2016). 

Several  alternative  assessment  studies  have  been  applied  to  phthalates  to  identify  and  assess 
alternatives. Studies vary in scope, ranging from alternative phthalates (high molecular volume), non-
phthalate  plasticisers  and  alternative  materials.    The  wide  variability  in  the  level  of  information 
available  on  alternative  solutions  makes  it  difficult  to  draw  definitive  conclusions  on  human  and 
environmental risks of alternatives. Differences in life-cycle attributes add complexity to the problem.  
According  to  ECHA’s  SEAC  and  RAC  opinions,  technically  feasible  alternative  plasticisers  are 
available at similar or slightly higher prices for all uses in articles in the scope of the 2018 proposed 
restriction (ECHA 2018). EFSA has assessed a number of plasticisers, which are known to be used as 
replacements in food contact materials and which have subsequently been authorised in plastic FCM. 
Alternatives  generally  have  more  benign  human  health  and  environmental  hazard  and  risk  profiles, 
although  there  are  some  uncertainties  regarding  the extent  to  which  risks  will be  reduced  following 
substitution.  EFSA  will  consider  in  its  new  work  on  phthalates  whether  further  assessment  is  also 
needed of replacement plasticisers and similar substances. However, based on the current information, 
it can be concluded that the alternatives will lead to overall risk reduction. 

Lifecycle  attributes  are  essential  in  drawing  conclusions  on  the  impact  of  regulation  of  DEHP.  As 
regards recycling of PVC containing DEHP, for example, comparing the benefits of reduced overall 
DEHP exposure with the costs of constraints to PVC recycling involves a high degree of uncertainty. 
Conclusions  on  the  subject  are  thus  ultimately  driven  by  differences  in  values  and  priorities  set. 
Depending  on  the  role  of  various  actors  among  industry,  regulators  and  NGOs,  some  stakeholders 
have prioritised energy and CO2 saving targets, while others have prioritised reduction in exposure to 
toxic  phthalates.  The  Commission  however  needs  to  balance  all  the  different  interests  when 
evaluating impact of regulatory measures. 

217 

 
 
 
 
5  Comments on fitness check evaluation criteria 

Comments  on 
coherence 

  Under REACH, the use of DEHP contained in recycled PVC to produce certain 
articles  from  recycled  PVC  was  authorised  in  2016  (currently  under  review). 
This authorisation is only applicable if recycled PVC has reached end-of-waste 
as regulated under legislation on waste. However, no end-of waste criteria have 
been  established  so  far  in  the  EU,  and  at  Member  State  level,  national 
authorities are to take end-of-waste decisions as and if appropriate. So far, no 
such cases have been notified to the Commission. 

  Restricting articles containing DEHP under REACH in parallel to the REACH 
authorisation  requirement,  which  is  applicable  only  to  EU  companies, 
addressed the issue of imported products.   

toxicity 

the  same  hazard, 

  The  scientific  opinions  issued  by  ECHA  and  EFSA  on  DEHP  and  other  low 
molecular  weight  phthalates  considered 
to 
reproduction  and  toxicological  data.  Both  used  a  dose  addition  model  for  the 
combined risk assessment. ECHA’s assessment pointed to evidence of risk to 
human  health  from  combined  exposure  using  mainly  biomonitoring  data. 
Exposure  via  food  contributes  to  the  observed  exposure.  EFSA’s  assessment 
pointed  to  combined  exposure  not  resulting  in  exceeding  group-based  TDIs. 
EFSA’s  assessment  did  not  consider  DIBP  (not  authorised  in  FCM)  and 
focussed on dietary exposure. The two assessments differ in scope (chemicals, 
exposure sources), exposure information used (e.g. food intake estimates) and 
to  a  minor  extent  to  methods  (e.g.  population  age  grouping,  absorption 
assessment factor). Differences in results are mainly determined by the specific 
policy  question  being  addressed  but  some  differences  in  the  assessment  exist 
for the same question (e.g. food intake estimates). 

 

  Differences in the risk  management approach follow from the different scope 
of  regulations  and  risk  assessments  performed.  The  consequences  for  the 
achievement  of  the  objectives  (exposure  and  risk  reduction)  cannot  be 
quantified at present.    
 Variations in risk management and approaches taken under different pieces of 
legislation (REACH, FCM) may be justifiable when considering the objectives 
and  scope  of  the  individual  pieces  of  legislation.  However,  potential 
differences  in  the  outcomes  of  risk  assessments  of  the  same  substances  or 
group of substances considering the framework as a whole may undermine the 
science  and  subsequent  risk  management  action.    The  situation  points  to  the 
need  for  an  integrated  exposure  assessment  framework  accounting  for 
contributions from different exposure sources in a systematic way.  

  Regulatory  action  and  risk  assessments  were  launched  under  the  various 
legislations  at  different  points  in  time  by  different  actors.  With  the  SVHC-
Roadmap  to  2020184,  a  Regulatory  Management  Option  Analysis  was 
introduced  under  REACH  that  is  looking  on  potential  regulatory  measures 
under all legislations and sectors. However, this coordinative tool did not lead 

184https://echa.europa.eu/svhc-roadmap-to-2020-implementation 

218 

 
 
 
                                                      
Comments  on 
effectiveness 

to  initiating  regulatory  action  on  DEHP  outside  of  REACH  since  it  was 
developed  later  and  after  the  first  regulation  of  DEHP  under  REACH  has 
started. 

  Regulatory assessments included reviews of scientific information available at 
the time of assessment and took advantage of peer reviewed, quality data (e.g. 
biomonitoring, non-animal methods). Information from scientific sources often 
plays  a  decisive  role  for  high  tier  assessments  and  are  hence  important  in 
regulatory  assessments.  This  was  the  case  for  the  2018  REACH  restriction 
when  human  biomonitoring  data  was  instrumental  to  support  the  2018 
phthalates  REACH  restriction.  Similarly,  exposure  data  from  the  scientific 
literature  was  essential  for  the  EFSA  2019  risk  assessment  because  of 
analytical  limitations  in  measurements  from  the  EFSA  chemical  occurrence 
database. 

  Regulatory  action  on  DEHP  and  other  phthalates  started  before  ED  specific 
provisions  were  in  place.  These  included  the  1999  ban  on  DEHP  in  toys  and 
childcare articles, the classification as toxic for reproduction in 2001, the ban to 
supply  DEHP  to  the  general  public,  the  ban  in  cosmetic  products  in  2004, 
restrictions in FCM in 2007 and the inclusion in the REACH authorisation list 
in  2011.  Regulatory  assessments  and  actions  followed  the  increasing 
knowledge on DEHP over time. 

  DEHP  is  tightly  controlled  by  current  EU  legislation.  Under  REACH  it  is 
subject to authorisation since 2011, to restrictions on toys and childcare articles 
on the supply to the general public and to a broad restriction in articles since 
2018. It is also restricted and subject to authorisation regimes under the RoHS. 
It is allowed for use in plastic FCMs only for such materials that comply with 
restrictions  including  specific  migration  limits,  and  in  medical  devices  based 
on case-by-case risk-benefit considerations and assessment of alternatives. It is 
banned from use in cosmetics due to its classification as toxic for reproduction 
under CLP. 

  The  additional  inclusion  of  ED  effects  on  human  health  and  on  the 
environment  in  the  SVHC  list  triggered  risk  provisions  for  risk  assessment 
(Chemical Safety Report) and risk communication (Safety Data Sheets). Once 
these  properties  are  included  also  in  the  DEHP  listing  in  Annex  XIV  of 
REACH,  the  ED  effects  would  need  to  be  considered  in  applications  for 
authorisations  and  in  reviews  of  authorisation.  Furthermore,  listing  of  ED 
effects to the environment will trigger an obligation to obtain authorisations in 
other sectors (FCM, medical devices) that until then were exempted from this 
obligation. This development also prompted the re-designation of DEHP from 
a Priority to a Priority Hazardous Substance under the WFD. 

  According 

to  ECHA 

the  proposed  REACH  restriction 

is  capable  of 
significantly reducing the risks to human health of combined exposure (RCRs 
are expected to be reduced to levels equal to or below 1 at the 95th percentile) 
within a reasonable period of time, starting from 2020, although some delay is 
likely to be caused by the service-life of articles in use. 

  There  is  evidence  of  reduced  human  exposure  to  regulated  low-molecular-
weight phthalates including DEHP since the early 2000s. German data indicate 

219 

 
 
that human exposure to di-isononyl phthalate (DINP), one of the most common 
phthalate alternatives to DEHP has remained constant or even slightly declined 
in  the  last  years,  possibly  indicating  a  move  to  non-phthalate  alternatives,  at 
least in Germany. 

  DEHP and other low-molecular-weight phthalates are being replaced by high- 
molecular-weight phthalates, non-phthalate alternatives and other solutions.  
Yet,  analyses  by  inspecting  enforcement  authorities  have  found  incompliant 
products (e.g. toys) especially from imports. 

Comments  on 
efficiency 

Comments  on 
EU 
added 
value 

  Hazard assessments of DEHP have been done at various points in time under 
various  pieces  of  legislation  (e.g.  CLP,  REACH,  FCM,  WFD).  Considering 
the  whole  framework,  it  would  be  more  efficient  to  do  a  single  hazard 
assessment  per  substance  or  group  of  substances  by  fully  coordinating  the 
work  programme  of  respective  agencies/committees.  Despite  ongoing  efforts 
in  harmonising  approaches,  the  framework  is  currently  not  optimised  for 
efficiency.  

  DEHP  and  the  other  low-molecular-weight  phthalates  are  mostly  regulated  at 
EU level under REACH and RoHS. This includes toys and childcare articles, 
electric  and  electronic  articles  using  DEHP  in  plastic  material  and  all  other 
restricted  under  REACH  as  well  as  REACH  authorisation 
articles 
requirements. 

  In  some  Member  States,  further  restrictions  apply  to  DEHP  and  other 
phthalates  in  non-plastic  FCMs,  such  as  rubber.  These  restrictions  are 
inconsistent with each other indicating a possible need for a more coherent EU 
approach. 

6  References 

COWI,  IOM,  Entec  UK.  2009.  Data  on  manufacture,  import,  exposure,  uses  and  releases  of  bis(2-
ethylhexyl)phthalate  (DEHP)  as  well  as  information  on  potential  alternatives  to  its  use.    Contract 
ECHA/2008/02/SR5/ECA.227: https://echa.europa.eu/documents/10162/13640/tech_rep_dehp_en.pdf 

EC (DG Environment) – Enter UK. 2011. Technical support for the impact assessment of the review 
of  priority  substances  under  Directive  2000/60/EC.  https://circabc.europa.eu/sd/a/d6673532-e862-
4d40-ab5f-8aaffc766f58/DEHP.pdf 

EC (DG Environment). 2017. Study for the strategy for a non-toxic environment of the 7th EAP. Sub-
study b: chemicals in products and non-toxic material cycles. 

EC.  2016.  Commission  Implementing  decision  of  16.6.2016  granting  an  authorisation  for  uses  of 
bis(2-ethylhexyl) phthalate (DEHP) under Regulation (EC) No 1907/2006 of the European Parliament 
and of the Council. C(2016) 3549. 

EC.  2018.  Communication  of  the  implementation  of  the  circular  economy  package.  Options  to 
address the interface between waste and chemical regulation 2018 SWD study on COM 2018/32 on 
(with Box 1 on DEHP). https://ec.europa.eu/docsroom/documents/27321 

220 

 
 
 
ECB  –  Sweden.  2008.  European  Union  risk  assessment  report-  bis(2-ethylhexyl)phthalate  (DEHP) 
https://echa.europa.eu/documents/10162/e614617d-58e7-42d9-b7fb-d7bab8f26feb 

ECHA. 2010. Evaluation of the new scientific evidence concerning the restrictions contained in annes 
XVII to regulation (EC) No 1907/2006 (REACH)  – Review of new available information for bis(2-
ethylhexyl)phthalate 
(DEHP). 
https://echa.europa.eu/documents/10162/13641/dehp_echa_review_report_2010_6_en.pdf 

ECHA.  2012.  RAC  and  SEAC  opinion  on  an  Annex  XV  report  proposing  restriction  on  four 
phthalates.  Registry  of  restrictions  intentions  until  outcome.  https://echa.europa.eu/registry-of-
restriction-intentions/-/dislist/details/0b0236e180d73895. 

ECHA 2017a. Background document to the Opinion on the Annex XV dossier proposing restrictions 
on  four  phthalates  (DEHP,  BBP,  DBP,  DIBP)  https://echa.europa.eu/registry-of-restriction-
intentions/-/dislist/details/0b0236e1806e7a36 

ECHA  2017b.  Annex  A  to  the  background  document  to  the  Opinion  on  the  Annex  XV  dossier 
proposing 
DIBP) 
phthalates 
(https://echa.europa.eu/documents/10162/1c33302c-7fba-a809-ff33-6bed9e4e87ca) 

restrictions 

(DEHP, 

DBP, 

BBP, 

four 

on 

ECHA. 2019. Authorisation decisions list: https://ec.europa.eu/docsroom/documents/37301. 

EFSA.  2005.  Opinion  of  the  Scientific  Panel  on  Food  Additives,  Flavourings,  Processing  Aids  and 
Material in Contact with Food (AFC) on a request from the Commission related to Di-Butylphthalate 
(DBP) for use in food contact materials. The EFSA Journal 242: 1-17. 

EFSA.  2005.  Opinion  of  the  Scientific  Panel  on  Food  Additives,  Flavourings,  Processing  Aids  and 
Material  in  Contact  with  Food  (AFC)  on  a  request  from  the  Commission  related  to  butyl-benzyl-
phthalate (BBP) for use in food contact materials. The EFSA Journal 241: 1-14. 

EFSA.  2005.  Opinion  of  the  Scientific  Panel  on  Food  Additives,  Flavourings,  Processing  Aids  and 
to 
Material 
ethylhexyl)phthalate (DEHP) for use in food contact materials. The EFSA Journal 243: 1-20. 

in  Contact  with  Food  (AFC)  on  a  request  from 

the  Commission  related 

EFSA. 2019. Draft update of the risk assessment of di-butylphthalate (DBP), butyl-benzyl-phthalate 
(BBP),  bis(2-  ethylhexyl)phthalate  (DEHP),  di-isononylphthalate  (DINP)    and  di-isodecylphthalate 
(DIDP) 
materials. 
https://www.efsa.europa.eu/sites/default/files/consultation/consultation/Phthalates_in_plastic_FCM_d
raft_opinion_for_public_consultation.pdf 

contact 

food 

use 

for 

in 

Göen  T,  Dobler  L,  Koschorreck,  Müller  J,  Wiesmuller  GA,  Drexler  H,    Kolossa-Gehring  M.  2011. 
Trends  of  the  internal  phthalates  exposure  of  young  audults  in  Germany  –  Follow  up  of  a 
retrospective human biomonitoring study. Int J Hygiene Environ Health. 2015 :36-45.  

Greenpeace  International  Report.  2005.  Perfume,  an  Investigation  of  Chemicals  in  Perfumes. 
https://www.greenpeace.org/usa/wp-content/uploads/legacy/Global/usa/report/2007/7/perfume-an-
investigation-of.pdf   

JRC.  2012.  End-of-waste  proposals  for  waste  plastic  for  conversion  –  Technical  proposals. 
https://susproc.jrc.ec.europa.eu/activities/waste/documents/Plastics2ndworkingdoc23may2012.pdf 

221 

 
 
 
Koch  HM,  Rüther  M,  Schültze  A,  Conrad  A,  Pälmke  C,  Appel  P,  Bruning  T,  Kolossa-Gehring  M. 
2016.  Phthalate  metabolites  in  24-h  urine  samples  of  the  German  Environmental  Specimen  Bank 
(ESB) from 1988 to 2015 and a comparison with US NHANES data from 1999 to 2012. Int J Hygiene 
Environ Health 220: 130-141.  

Pivnenko, K., Laner, D., and Astrup, T.F., 2016, 'Material Cycles and Chemicals: Dynamic Material 
Flow Analysis of Contaminants in Paper Recycling', in Environ Sci Technol 50: 12302−12311. 

SCHEER (Scientific Committee on Health, Environmental and Emerging Risks). 2019. Guidelines on 
the  benefit-risk  assessment  of  the  presence  of  phthalates  in  certain  medical  devices  covering 
phthalates  which  are  carcinogenic,  mutagenic,  toxic  to  reproduction  (CMR)  or  have  endocrine-
disrupting (ED) properties, final version adopted at SCHEER plenary on 18 June 2019. 

Schöeters et al. 2017. Three cycles of human biomonitoring in Flanders – Time trends observed in the 
Flemish environment and health study. Int J Hygiene and Environ Sci 220 : 36-45.  

Tranfo  G,  Caporossi  L,  Pigini  D,  Capanna  S,  Papaleo  B,  Paci  E.  2018.  Temporal  trends  in  urinary 
phthalates concentrations in two  populations:  effects of REACH authorisation after five years.  Int J 
Environ Res Public Health (15) : 1950. 

222 

 
 
 
 
 
Annex 5C. Case Study: nonylphenol 

1  Case  study  factsheet:  overview  of  concerns  for  human  health 

and environment and main regulatory intervention 

Product 
(possible 
sources) 

types 
exposure 

Nonylphenol  (NP)  has  been  used  for  the  following  purposes  or  in  the 
following  articles.  The  listed  uses  have  been  restricted  or  otherwise 
regulated in the EU, with few authorised uses for specific applications. 

- Industrial processes 
- Textiles 
- Detergents 
- Pesticides and biocides 
- Hair care products  

Exposure pathways of 
(human 
concern 
health 
and 
environment) 

Concerns are mainly for exposure of aquatic ecosystems, via domestic and 
industrial  wastewater  emissions.  Nonylphenol  emissions  occur  during  its 
production  and  subsequent  use  as  well  as  from  the  breakdown  of  some 
products  containing  a  nonylphenol  group,  particularly  nonylphenol 
ethoxylates (NPnEO).  

Concerns  for  human 
the 
health 
environment 

and/or 

Regulatory 
and risk assessment 

hazard 

Nonylphenols  act  as  estrogen  receptor  agonists  and  may  have  anti-
androgenic properties causing adverse effect in fish and amphibians.  

  2001 - Classified as Cat 2  toxic for reproduction and as Cat 1 chronic 
toxic for the aquatic environment under CLP (Directive 2001/59/EC) 
  2001 - Nonylphenol proposed as priority hazardous substance under the 

WFD (COM/2001/17) 

  2002  –  European  Union  Risk  assessment  report  on  nonylphenols  and 
nonylphenol  ethoxylates  under  the  Existing  Substance  regulation 
793/93 

  2005 Opinions of the Commission Scientific Committee on Consumer 
Products  (SCCP/0888/05  and  SCCP/0913/05)  related  to  the  listing  of 
NP as prohibited substance in cosmetic products due to its classification 
as toxic to reproduction 

  2005  -  EQS  established  for  annual  average  and  maximum  exposure 

under the WFD 

  2012  -  Identification  of  NP  by  ECHA  as  a  substance  of  very  high 
concern (SVHC) for ED effects in the environment based on a proposal 
by the Germany 

  2013 - Identification of NPnEO by ECHA as a SVHC, as a precursor to 
NP, itself already identified for ED effects in the environment based on 
a proposal by the Germany 

  2014  -  ECHA  RAC  and  SEAC  opinions  on  the  Annex  XV  dossier 

223 

 
 
 
 
 
Risk 
measures 

management 

proposing  restrictions  on  NP  and  NPnEO  (branched  and  linear)    in 
textile clothing, fabric accessories and interior textile articles (including 
their prints) that can be washed in water if they contain nonylphenol or 
nonylphenol ethoxylate alone or in combination in concentrations equal 
or higher than 100 mg/kg textile. 

  2016 - Second review of the priority substances list under the WFD, led 
by  JRC  leading  to  JRC  proposal  to  revise  NP  EQS  (2020,  pending 
review and approval). 

  2019 Proposal by France for the identification of TNPP as SVHC.  

  2001 - proposed identification as priority hazardous substance triggers 
WFD art 16(1) requiring cessation or phasing out of aquatic emissions  
  2003  -  Restriction  for  the  use  of  NP  and  NPnEO  at  concentrations 
>0.1%  by  weight  (Directive  2003/53/EC).  Restriction  incorporated  in 
REACH (Annex XVII entry 46). 

  2005  -  Included  in  of  the  list  of  prohibited  ingredients  under  the 
legislation on cosmetic products (however, NP was already restricted in 
cosmetic products with Directive 2003/53/EC) 

  2012  -  identification  of  NP  as  a  substance  of  very  high  concern 

(SVHC) for ED effects in the environment 

  2013  identification  of  NPnEO  as  a  substance  of  very  high  concern 

(SVHC) for ED effects in the environment 

  2017  -  NPnEO  included  in  REACH  Annex  XIV    authorisation 
regime applies: deadline for application July 2019, sunset date January 
2021 

  2016  -  REACH  Restriction  of  NPnEO 

textile  articles  at 
concentrations > 0.01% weight which will enter into application after 3 
February 2021 (Regulation (EU) 2016/26) 

in 

  2020 (ongoing) EQS currently being revised under the WFD, based on 

new ecotoxicological data  

2  Substance profile 
Nonylphenol (NP) consists of a family of long-chain alkylphenols composed of a phenol group and an 
attached linear or branched nine carbon tail, usually in the 4- position (4- or para-nonylphenol). It is 
structurally related to other long chain alkylphenols and in particular octylphenol.  Nonylphenol is a 
non-ionic amphipathic substance, composed of a hydrophobic and a hydrophilic part, and it acts as a 
surfactant  in  aqueous  solutions.  It  has  been  classified  as  inherently  biodegradable  (EC  2002). 
Biodegradation  depends  on  the  isomers  with  lower  degradability  at  higher  degrees  of  branching. 
Environmental  degradation  rates  also  depend  on  ecological  conditions  such  as  presence  and 
adaptation of microbial communities (EC 2002). 

NP is mainly used as an intermediate in the production of various NP derivatives. The derivatives are 
formulated into mixtures. Nonylphenol ethoxylates (NPnEOs) are the most common substances based 
on  NP.  They  are  part  of  the  alkylphenol  ethoxylate  group,  a  family  of  non-ionic  surfactants.  As  a 
surfactant NPnEOs has historically been used as a tenside in household and commercial products (e.g. 
personal  care, laundry products and cleaners) (Kjølholt et al. 2007, in ECHA 2013).  Short-chained 
NPnEOs are used in detergents and other cleaning products. NPnEOs with chains of medium length 

224 

 
 
(between 10 and 30 ethoxylates) are used as emulsifiers, i.e. they help to form stable systems of more 
fat  in  less  water.  Long-chained  NPnEOs  (with  up  to  80  ethoxylates)  can  be  used  as  dispersants; 
because of their ability to retain small particles in solutions. NP is also used as a catalyst in the curing 
alkydes 
binder, 
and 
of 
(www.kemi.se/flodessok/floden/kemamne/nonylfenol.htm).  

various 

epoxy 

resin 

e.g. 

as 

in 

a 

The  use  of  NP  and  NPnEO  in  several  applications  of  cleaning  products  as  well  as  for  other 
applications  for  end  use  has  been  restricted  in  recent  years.  Data  on  market  volumes  and  end  use 
applications are available from the end of the 1990´s. It is difficult to find up-to-date information on 
market  volumes,  but  one  could  presume  that  for  all  restricted  applications  the  volumes  are  lower 
today  than  they  were  10-15  years  ago.  In  the  late  1990´s  NPnEOs  represented  80  to  90%  of  the 
alkylphenol  ethoxylates  used  in  the  EU  (by  tonnage)  (Postle  et  al  2003,  in  ECHA  2013).  NP  and 
NPnEO are however still  used outside the EU as detergents and  auxiliaries in the  manufacturing  of 
textile  articles.  According  to  EU  statistics  on  the  import  of  textiles  the  annual  NPequ  release  is 
estimated to be 257 tonnes (ECHA 2013).  

Although NP is not used in the manufacturing of the textile it could be unintentionally added to the 
textile as a contaminant in low concentrations from the degradation of NPnEOs in the manufacturing 
process.  NPnEOs  could  be  unintentionally  added  to  textiles  during  the  manufacturing  process  by 
using  contaminated  water  in  the  washing  processes,  by  leakage  from  lubricants  in  the  process 
equipment or by contamination by other fabrics during transport or storage (ECHA 2013).  

2.1

  Exposure pathways of concern  

Human exposure 

Consumer exposure is low. Worker exposure may have been significant for certain scenarios such as 
spray application of speciality paints (EC 2002), before restrictions were put in place. However, these 
exposures were not the leading reason for regulatory intervention. 

Environmental exposure  
Environmental exposure of nonylphenol occurs during its production and subsequent use. It may also 
occur  due  to  the  breakdown  of  some  products  containing  a  nonylphenol  group,  particular  NPnEOs 
(EC 2002). NPnEOs degrade to NP, especially under anaerobic conditions. Even though only about 
2.5% of the ethoxylates in influents may be ultimately emitted as NP to surface water (EC 2002), this 
transformation contributes significantly to the overall NP output of sewage treatment plants. 

Uses and emissions have  decreased since 2003,  when the restriction on uses of 4-nonylphenols and 
their ethoxylates came into force. Before restrictions were put in place, the majority of emissions to 
surface water came from urban wastewater treatment plants originating from industrial sites emitting 
into  the  public  sewage  system,  from wide dispersive application of products (e.g.  paints,  painted  or 
printed articles) or from washing of imported textiles where 4-nonylphenols and their ethoxylates are 
present  as  contaminants  from  the  production  process  (EC  2002).  The  background  document  to  the 
opinion  on  the  restriction  proposal  on  NP  and  NPnEO  published  in  2014  discusses  remaining 
emission sources in the EU (ECHA RAC and SEAC 2014).  

225 

 
 
 
 
 
2.2

  Effects on human health and the environment 

Human Hazard 

Some estrogenic activity was observed in in-vitro and in-vivo studies (EC 2002), which determined it 
classification  as  category  2  reproductive  toxicant.  However  endocrine  mediated  effects  on  human 
health have not been the leading reason for regulatory intervention. 

Environmental Hazard  

Nonylphenols act as estrogen receptor agonists. Competitive ligand-binding studies demonstrated that 
NPs can displace specifically bound E2 from the ER ligand-binding pocket. The relative potency of 
NPs compared to 17ß-estradiol ranged from 0.94 10-5 to 0.44 10-2 for aquatic species (ECHA 2012, 
Annex XV dossier proposal for SVHC listing). Based on the information for the different isomers, it 
can be concluded, that the estrogen receptor activation potency is comparable for linear and branched 
nonylphenols.  Binding  of  NPs  to  the  ER  leads  to  activation  of  the  ER-mediated  pathway  and 
consequently to transcriptional activation of typically estrogen-responsive genes.  

Moreover,  there  is  some  indication  that  NPs  may  be  able  to  interfere  with  other  nuclear  receptor-
mediated  pathways.  Thus,  NPs  were  demonstrated  to  inhibit  androgen-mediated  gene  expression  in 
vitro. 

NPs  act  as  endocrine  disruptors  in  fish  i.e.  that  the  substance  alters  the  function  of  the  endocrine 
system  and  consequently  causes  adverse,  population  relevant  effects.  In  vivo  data  for  several  fish 
species  show  that  this  holds  true  for  a  variety  of  different  species.  Overall  indication  of  estrogen 
activity was observed in all fish species tested. Estrogen activity started at the concentration of 1µg/L 
(O.mykiss)  with  respect  to  increased  vitellogenin  and  between  11.6µg/L  (O.latipes,  testis-ova)  and 
36.8µg/L  (O.mykiss,  sperm  stages)  with  respect  to  histological  changes.    In  three  fish  species 
(O.latipes, P.reticulata, D.rerio) observed effects on apical  endpoints are very likely to  be estrogen 
mediated. In another species (O.mykiss) and the viviparous fish there is strong evidence for endocrine-
mediated apical effects (ECHA 2012).   

In-vivo data on amphibians and invertebrate species suggest that organism groups other than fish may 
be adversely affected by exposure to NP at concentrations in the low µg/L range and below. Effects 
exerted in two frog species, R. sylvatica and R. pipiens, on gonadal sexual differentiation and changes 
in sex-ratio fit to an estrogen-like mode of action (ECHA 2012). 

3  Regulating nonylphenols in EU legislation 

The environmental risks posed by nonylphenols have been known from the 1980s. In Europe, several 
initiatives  were  introduced  to  reduce  emissions.  The  most  significant  of  these  was  the  1992  Paris 
Commission  (PARCOM)  commitment  on  the  part  of  members  to  “take  concerted  action  within  the 
framework  of  the  competent  international  forums  to  substitute  the  use  of  the  NPs  and  NPnEOs 
(among other listed chemicals) by less hazardous or preferably non-hazardous substances where these 
alternatives  are  available”.  Under  PARCOM  Recommendation  92/8,  contracting  parties  agreed  to 
phase out the use of NPnEOs as cleaning agents for domestic uses by 1995 and for industrial uses by 
2000.  Hence, significant reductions in use of NPs and NPnEOs had already occurred by 1999 (EC 
2016). 

226 

 
 
 
At  EU  level,  the  use  of  NPs  and  NPnEOs  is  mainly  regulated  under  REACH.  In  some  cases, 
regulatory  assessments  and  interventions  went  in  parallel  with  octylphenol.  Additional  provisions 
apply  under  the  WFD  regarding  the  identification  of  nonylphenol  as  a  priority  hazardous  substance 
(Figure 18.1), which has implications for treatment standards of the Integrated Pollution Prevention 
and Control (IPPC) Directive. 

Figure 18.1. Nonylphenol case study: illustration of applied provisions across legislation 

3.1

  Regulating nonylphenols in REACH 

Nonylphenol and its ethoxylates were regulated, before REACH came into force. The UK competent 
authorities carried out on behalf of the EU a risk assessment covering both environmental and human 
health  concerns  under  the  provisions  of  Regulation  (EC)  793/93  (EC  2002).  Results  of  the  risk 
assessment  identified  the  need  to  reduce  environmental  risks  at  both  regional  and  local  scales. 
Following  a  conventional  approach  for  the  aquatic  assessment,  a  predicted  no  effect  concentration 
(PNEC) of 0.33 µg/L was calculated from the lowest NOEC of 3.3 µg/L on the biomass algal growth 
(S. subspicatus). The algal growth study used for the PNEC derivation was not linked to an endocrine 
modality. Even for other aquatic species including fish, concentrations at which estrogenic effects are 
observed  appeared  to  be  higher  than  those  producing  other  effects.  Therefore,  the  risk  assessment 
concluded that the derived PNEC should be protective for estrogenic effects in fish as well. 

227 

 
 
  
 
 
 
Risks to human health were also assessed for workers and consumers. Furthermore, the risks due to 
indirect  exposure  of  humans  via  the  environment  were  evaluated.  According  to  the  assessment,  the 
risk from the use of NP was considered to be adequately controlled for consumers as well as for most 
uses  leading  to  worker  exposure.  Similar,  no  risk  was  identified  for  human  exposure  via  the 
environment.  The  assessment  took  aggregated  exposure  into  account.  The  risk  assessment  report 
outlines, however, that for certain uses, i.e. the manufacturing of NP, its use as intermediate and the 
use  of  speciality  paints  containing  NP,  the safety margins were  relatively low. This conclusion  was 
based  inter  alia  on  results  of  a  two-generation-toxicity  study  that  revealed  slight  effects  possibly 
linked to an estrogenic mode of action (EC 2002). 

In  its  opinion  of  6  and  7  March  2001,  the  Scientific  Committee  on  Toxicity,  Ecotoxicity  and  the 
Environment  (CSTEE)  confirmed  the  conclusions  of  the  UK  assessment.  The  opinion  triggered  the 
restriction  of  nonylphenol  and  nonylphenol  ethoxylates  through  entry  46  of  Annex  I  of  Directive 
76/769/EEC  (Directive  2003/53/EC),  which  became  applicable  from  January  2005.  The  restriction 
applied  at  concentrations  equal  or  higher  than  0.1%  by  mass  for  use  in  industrial  and  institutional 
cleaning, domestic cleaning, textiles and leather processing, emulsifier in agricultural teat dips, metal 
working, manufacturing of pulp and paper, cosmetics and other personal care products and as a co-
formulant in plant protection and biocidal products. The restriction was later incorporated in Annex 
XVII of REACH (Regulation 552/2009).  

The  German  competent  authority  filed  an  Annex  XV  dossier  proposing  the  identification  of 
nonylphenol (ECHA  2012)  as  an  SVHC  due  to  serious  effects  to  the  environment  giving  rise  to  an 
“equivalent level of concern” to other SVHCs due to meeting the classification criteria for CMRs Cat. 
1A/1B  or  because  they  are  persistent,  bioaccumulative  and  toxic  (PBT)  or  very  persistent  and  very 
bioaccumulative (vPvB) (REACH Article 57(f)).  

The  SVHC  dossier  reviewed  an  extensive  list  of  studies  that  described  over  30  in  vitro  assays  on 
estrogenic activity (e.g. binding assays, reporter gene assays, Yeast estrogenic transactivation (YES) 
assays  and  assays  analysing  vitellogenin  induction  in  primary  hepatocytes)  as  well  as  34  in  vivo 
assays with various fish species. Collectively, they have provided strong evidence of adverse effects 
in  fish  species  mediated  by  an  estrogenic  modality.  Regarding  amphibians  and  invertebrates,  no 
definitive conclusion could be drawn.  

The  proposal  for  SVHC  identification  was  agreed  by  the  Member  State  Committee  in  December 
2012. According to the Support Document of the MSC (ECHA 2012), based on the data mentioned 
above, NP fulfils the WHO/IPCS definition of an endocrine disruptor. The probable serious effects to 
the environment were considered of “equivalent concern” to other SVHCs.  

According to the MSC the “equivalent level  of concern” criterion  is fulfilled since effects  observed 
after exposure to NP are considered to impair population stability and recruitment of a wide range of 
fish species. Effects may occur even after short term exposure and thus may result in impairments in 
regions  other  than  those  where  exposure  occurred  and  possibly  on  a  long-term  basis.  Effects  may 
influence a wide range of taxa. A safe level of exposure to NP may exist, but it is difficult to estimate 
it.  

Almost in parallel, also NPnEOs were proposed for SVHC identification by Germany (ECHA 2013a). 
The rationale for inclusion in the candidate list was the fact that 4-Nonylphenol, branched and linear, 
ethoxylated (4-NPnEO) degrade to 4-nonylphenol, branched and linear, either already in wastewater 
treatment plants, or via further degradation processes in sediments and soils receiving sewage sludge. 

228 

 
 
In addition, available information reviewed for NPnEO indicate that short chain ethoxylates (NP1EO 
and NP2EO) possibly show endocrine activity themselves, with in vitro and in vivo estrogenic activity 
nearly as high (within a factor of 10) or similar to the endocrine activity of 4-nonylphenol. However, 
information on endocrine-mediated adverse effects caused by NPnEO was not available, and therefore 
a conclusion on whether NPnEOs are endocrine disruptors themselves could not be drawn. NPnEOs 
were identified as SVHCs and included in the candidate list in July 2013. 

Nonylphenol  ethoxylates  were  later  in  2015  prioritised  together  with  octylphenol  ethoxylates 
(OPnEOs)  for  inclusion  in  Annex  XIV  (authorisation  list)  and  included  in  that  Annex  in  2017  with 
latest application date July 2019 and sunset date January 2021. 

The  restriction  in  place  since  2005  and  the  authorisation  regime  established  for  nonylphenol 
ethoxylates  through  the  inclusion  in  Annex  XIV  apply  to  a  wide  range  of  substance  uses.  Starting 
from  the  1990s  manufacture,  uses,  environmental  emissions  and  aquatic  exposure  of  nonylphenol 
decreased (AMEC 2012 in ECHA 2014b, see also Section 4.1).  

However,  monitoring  data  obtained  from  European  water  bodies  between  2006  and  2012 
demonstrated that a small proportion of freshwater bodies and some marine waters in more than one 
MS  were  at  risk  due  to  NP  exposure  (ECHA  RAC  and  SEAC  2014b). This  situation  motivated  the 
Swedish  competent  authority  to  prepare  in  2013  a  proposal  for  restriction  for  NP  and  NPnEO  at 
concentrations equal to or higher than 100  mg/kg in textiles (ECHA 2013b). The Annex XV report 
estimated  that  release  from  washing  of  textiles  contributes  to  approximately  half  of  the  estimated 
aquatic emissions of NP and imported textile articles are identified as a major source. 

The Swedish competent authority (CA) presented a section on risk characterisation for environmental 
compartments  of  concern  (freshwater,  marine,  sediments  and  terrestrial).  This  was  done  following 
standard  procedures  for  environmental  risk  assessment  on  nonylphenol.  Exposure  concentrations 
(PEC) used in the risk assessment were based on the 90th percentile of monitoring data, most of which 
were obtained under the Water Framework Directive. Several approaches for calculating Predicted No 
Effect  Concentrations  (PNECs)  were  included  using  data  from  freshwater  or  marine  organisms  and 
either only classical endpoints not explicitly related to endocrine disruption or applying an additional 
AF  of  10  to  take  into  account  ‘additional  uncertainty’  due  to  endocrine-mediated  effects.  Another 
approach was based on species sensitivity distributions (for freshwater or for freshwater and marine 
species). Risk ratios exceeding 1 were reported when combined effects of nonylphenol, nonylphenol 
ethoxylates  and  their  degradation  products  (nonylphenol  ethoxycarboxylates)  were  assessed  using  a 
toxicity equivalent approach for the marine compartment at EU level and in freshwater for 8 to 12 EU 
countries out of a total of 25 EU countries and Norway, but not for freshwater at the EU median level. 
When  introducing  the  additional  assessment  factor  of  10  the  risk  characterisation  ratios  in  the 
combined toxicity assessment exceeded 1 at the EU median level for both the marine and freshwater 
compartments.  It  was  also  noted  that,  although  effects  on  growth  by  itself  would  not  lead  to  a 
conclusion that a chemical is an ED in fish, together with available in-vitro and in-vivo mechanistic 
data and ED-related adverse effects in certain fish species (e.g. skewed sex ratio) it was reasonable to 
assume that the effects are endocrine related. Finally, the Swedish CA concluded that identifying safe 
concentration limits for all possible endpoints within the endocrine system that can be affected by ED 
is not possible within the current test method guidelines and would be inconsistent with the objective 
in REACH to reduce animal testing (ECHA 2013b). 

In its opinion (ECHA SEAC and RAC 2014b), the RAC first noted that the derived PNECs based on 
traditional, apical endpoints are similar independent of the method used or of whether freshwater or 

229 

 
 
marine  taxa  are  considered.  Due  to  that,  and  based  on  traditional,  apical  endpoints,  RAC  derived  a 
PNECaqua of 0.4 µg/L for NP covering both freshwater and marine environments. 

RAC  further  noted  that  compared  to  traditional  apical  endpoints,  endocrine-mediated  effects  in  fish 
start  at  concentrations  almost  one  order  of  magnitude  lower.  For  other  taxa,  analogous  evidence  on 
relations between apical and indicative endocrine-related effect concentrations is less clear due to the 
prevalent  inconclusiveness  regarding  endocrine-related  modes  of  action  and  regarding  adversity  of 
available  observations  at  low  concentrations.  According  to  RAC,  the  current  knowledge  prevents  a 
firm conclusion on a mechanistic endocrine-related link with the observed adverse effects especially 
in  studies  with  invertebrates.  Some  observations  occurred  only  at  the  lowest  test  concentrations. 
Uncertainties also derived from the lack of adequate test protocols for some taxonomic groups. 

RAC took note that the dossier submitter considered the application of an extra AF when deriving a 
PNEC for NP as one option to deal with the uncertainties around endocrine-related effects. Limited to 
fish,  RAC  believed  lowering  the  PNEC  by  a  factor  of  5  might  cover  adverse  endocrine  effects. 
However,  RAC  explicitly  did  not  offer  an  opinion  about  whether  such  a  lowered  PNEC  would  be 
sufficiently protective for all taxonomic groups.  

RAC  further  pointed  to  the  ongoing  discussions  at  that  time  on  whether,  in  the  context  of  REACH 
authorisations, endocrine disruptors should be considered as having a threshold or not. Given that the 
discussion  was  still  ongoing,  RAC  considered  it  premature  to  provide  an  opinion  on  the  threshold 
nature of endocrine disruptors. 

As a pragmatic way for assessing the risks of the uses targeted by the restriction proposal RAC based 
the  risk  assessment  on  the  PNEC  derived  from  classical  endpoints.  RAC  argued  that  any  risk 
identified by this approach would already be sufficient for justifying the restriction, and any further 
consideration of endocrine-mediated effects or of combination effects would likely lead to a greater 
risk. 

The SEAC analysis of the restriction proposal evidenced that NP is not identified as used intentionally 
in textile processing. Consequently, the inclusion of Nonylphenol in the scope of the restriction was 
considered not justified because it would be practically difficult to implement and monitor and most 
likely not necessary to achieve the desired objective. Commission regulation 2016/26 put forward the 
restriction for certain uses of nonylphenol and nonylphenol ethoxylates in concentrations equal to or 
greater than 0.1% by weight (Annex XVII, entry 46a) and nonylphenol ethoxylates in textile articles 
(46a) in concentrations equal to or greater than 0.01% by weight. The proposed restriction is expected 
to effectively reduce the major part of NP/NPnEO that is estimated to be emitted from textile articles 
imported to the European Union.  

July  2019  marked  the  deadline  for  submitting  authorisation  applications  of  octyl-  and  nonylphenol 
ethoxylates to be able to continue their uses, following their inclusion in Annex XIV (entries 42 and 
43).  In  a  notice  issued  by  ECHA  to  provide  advice  to  applicants  for  authorisation  for  uses  of  octyl 
phenol ethoxylates (OPEs) and NPnEOs (ECHA RAC 2017) the RAC has elaborated its position on 
the feasibility of demonstrating a safe threshold for these substances, in line with the report issued by 
the Commission on the topic (COM 2016/814). The Commission report concluded that an endocrine 
disruptor  may  or  may  not  have  a  threshold.  As  for  other  substances  subject  to  the  authorisation 
requirement,  it  is  the  responsibility  of  the  applicant  to  demonstrate  that  a  threshold  exists  and  to 
determine that threshold in accordance with Annex I to REACH. Then, it is up to the RAC to assess 
the validity of the assessment and ultimately decide on the possible existence or not of this threshold. 

230 

 
 
The report also states that, in order to increase predictability and legal certainty for applicants, RAC 
has set on a case-by-case basis reference DNELs for threshold substances, or reference dose-response 
curves for non-threshold substances, which industry can use when applying for authorisation and that 
this practice applies also for EDs.  

Based  on  the  above,  RAC  pointed  out that  an  applicant  for  authorisation  can  propose  a  PNEC  or  a 
dose-response relationship. It is then up to the applicant to submit all necessary data, which RAC will 
assess. RAC indicated on which information it would pay particular attention. RAC also pointed out 
that  applicants  may  simply  choose  to  follow  in  their  application  the  same  approach  as  for  non-
threshold substances. In this case, the assessment of the application for authorisation would follow the 
approach for non-threshold substances or for PBTs/vPvBs, and the authorisation could, if appropriate, 
be  granted  if  it  is  shown  that  socio-economic  benefits  outweigh  the  risks  to  human  health  or  the 
environment,  and  there  are  no  suitable  alternative  substances  or  technologies,  as  provided  for  in 
REACH Article 60(3) and 60(4). The authorisation is subject to conditions, including monitoring, to a 
time-limited review and takes in to account all potential discharges, emissions and losses. 

Upon the initiative of the French competent authority, another substance has been identified by ECHA 
as  SVHC  due  to  the  presence  of  4-nonylphenol  as  an  impurity:  tris(4-nonylphenyl,  branched  and 
linear)  phosphite  (TNPP  if  it  contains    ≥  0.1%  w/w  of  4-nonylphenol  as  impurity  (ECHA  2019). 
TNPP can be produced with or without the occurrence of NP as impurity. It is used as an antioxidant 
to stabilise polymers and may be present in a variety of applications with a potential of exposure from 
articles,  polymers  (including  food  contact  materials)  or  mixtures  (e.g.  paints,  adhesives).  The 
substance was included in the Candidate List in July 2019. 

3.2

  Regulating nonylphenols under other chemical legislation 

Nonylphenol is restricted under REACH for use in cosmetics since 2003 (date of application: January 
2005), it is also included in Annex II of the Cosmetic Products Regulation because it is classified as 
Cat II toxic for reproduction under the CLP regulation.  

Neither  nonylphenols,  nor  their  ethoxylates  are  on  the  positive  list  of  substances  authorised  by  the 
Commission  Regulation  (EU)  N°10/2011  of  14  January  2011  relating  to  the  plastic  materials  and 
articles intended to come into contact with food.  

  Regulating nonylphenols under the Water Framework Directive 

3.3
The WFD applies a combination of generic and specific risk considerations from both experimental 
and  modelling  data  for  the  classification  of  chemicals  as  priority  substances  (PS)  and  priority 
hazardous substances (PHS).  

Nonylphenol was included in the first list of PS for its relatively high modelling-based ranking (#38) 
in  the  prioritisation  exercise,  combined  with  additional  evidence  of  environmental  occurrence  and 
endocrine disrupting effects (Klein et al 1999).  

The criteria for PHS  classification  consist of both hazard and risk  considerations (checks 1  to 6) as 
well as “additional considerations” (check 7), including the suspected endocrine disrupting potential 
(EC  2001).  In  the  case  of  nonylphenol  the  classification  was  mainly  motivated  by  evidence  for  a 
concern for the freshwater environments from the ECB risk assessment (ECB 4/15/00) under the pre-
REACH  regulation  793/93  showing  a  widespread  risk  to  or  via  the  aquatic  environment 
(COM/2001/17).  

231 

 
 
 
Identification of a substance as PHS according to art 16(1) of the WFD requires measures aiming at 
the cessation or phasing out of discharges, emissions and losses within an appropriate timetable not 
exceeding 20 years. 

Environmental Quality Standards were established in 2005 for Annual Average (AA-EQS: 0.33 µg/L) 
and  for  Maximum  Allowed  Concentration  (MAC-EQS:  2.1  µg/L)  in  surface  water,  together  with 
other specific quality standards for biota (EC 2005). Both AA-EQS and the MAC-EQS were derived 
following  the  guidance  for  the  derivation  of  a  PNEC  (Predicted  No  effect  Concentrations)  using 
conventional endpoints not explicitly linked  with endocrine effects, and an assessment factor of 10. 
The AA-EQS and the MAC-EQS were calculated from a 72-hours EC10 (biomass) with the freshwater 
alga  Scenedesmus  suspicatus,  and  from  a  96-hour  EC50  with  the  freshwater  invertebrate  Hyalella 
Azteca. Regarding endocrine disrupting potential the report states that “most of the tests indicate that 
estrogenic effects may start to occur at around 10-20 µg/l”, therefore the calculated PNECs should be 
protective for estrogenic effects in fish as well. 

The  EQS  are  currently  being  revised  considering  additional  ecotoxicological  data  available  (Ecotox 
Centre 2016). Significantly lower EQS values have been calculated in the proposed draft EQS dossier, 
currently under review (JRC 2020, unpublished draft) 

4  Impact of regulation 

  Reduced exposure 

4.1
There  have  been  considerable  efforts  to  phase  out  alkylphenols  since  the  1990s.  Use  of  NP  was 
estimated to be 78 500 tonnes per year in 1997 (EC 2002). A decrease of the use of NP in the EU was 
observed already in the years before due to the phase-out in detergents and for other uses (EC 2016). 
For  2010,  i.e.  before  further  regulatory  action  was  taken,  the  production  volume  in  the  EU  was 
estimated to be in the range of 10 000 to 50 000 tonnes/year (AMEC 2012 in ECHA 2014b). All the 
above  figures  include  the  use  of  NP  as  intermediate  for  the  manufacturing  of  NPnEOs  as  well  as 
polymers, epoxy resins or other substances. The use as an intermediate appears to be the main use of 
NP (with roughly 50-60% used for the manufacturing of NPnEO and 30-40% to produce polymers, 
epoxy resin and other substances) (ECHA 2014b). 

Since  its  listing  as  a  priority  substance  under  the  WFD  nonylphenol  has  been  subject  to  routine 
monitoring in the European wastewater, surface waters and biota. The decline in aquatic exposure is 
evidenced by analysing long-term temporal trends. For instance, concentrations in fish (bream, muscle 
tissue) caught in Germany diminished by 67% between 1995 and 2001 (EC 2016). 

A recent analysis of monitoring data obtained from 15 MSs (one MS dominates holding about 71.9% 
from all samples) for the period 2006-2014 demonstrates a reduction of risk posed by NP in European 
surface water (Table 18.1, D. Marinov and T. Lettieri, personal communication). 

Table 18.1. Risk quotient (RQ) of NP in European surface water, calculated as the ratio of the 95%ile 
measured concentrations to the newly proposed EQS (RQ=MEC(p95)/EQS (draft EQS =0.013 µg/l)). 

Year 
RQ 

2006 
236.5 

2007 
53.1 

2008 
27.7 

2009 
13.1 

2010 
4.6 

2011 
19.2 

2012 
10.9 

2013 
0.96 

2014 
0.77 

232 

 
 
 
 
Another  study  analysed  the  concentration  of  NP  in  the  Lambro  River,  a  tributary of  the  river  Po  in 
Northern  Italy,  receiving  high  amounts  of  industrial  and  domestic  wastewater  (Rusconi  et  al  2015). 
Two  monitoring  campaigns  in  2003/04  and  2009/10,  respectively  before  and  after  Directive 
2003/53/EC restriction (in force from 2005) as well as the start of operation of three new wastewater 
treatment  plants  (WWTPs)  in  the  city  of  Milan.  Data  showed  that  the  reduction  of  the  different 
analytes  in  the  period  ranged  from  70%  to  90%.  The  reduction  was  mostly  attributed  to  the 
substitution of NPnEO in industrial uses as demonstrated by a survey in the textile industrial district, 
with  the  entry  into  operation  of  the  new  municipal  WWTPs  contributing  about  10%  to  total  river 
loads. 

Unlike  certain  steroid  oestrogens,  there  is  no  strong  evidence  of  the  effects  of  NP  on  wildlife  fish 
populations  (Sumpter  2013).  In  recent  years,  the  combination  of  in-vitro  bioassays  measuring  total 
estrogenic  activity  in  water  samples  with  identification  of  substances  responsible  for  the  observed 
activity has improved the ability to quantify the contribution of single substances. Recent studies have 
confirmed  that  natural  and  synthetic  steroid  oestrogens  are  largely  responsible  for  the  observed 
estrogenic  activity  in  wastewater  effluents  and  freshwater  samples  (Miege  et  al  2009,  Tusova  et  al 
2019). In conclusion, to date it is not possible to link the observed decline in aquatic concentrations of 
NP with improved trends in biomarkers of effects or any other biological indicators. Increasing spatial 
and  temporal  coverage  of  effect-based  methods,  as  recommended  for  chemical  water  quality 
assessments  under  the  WFD  (JRC  2020)  could  provide  further  insights  on  the  link  between  aquatic 
exposure ecological effects of mixtures and individual components of estrogenic samples.  

  Shift to alternatives  

4.2
Due to the different functionality of nonylphenol ethoxylates, as a surfactant, emulsifier, etc., several 
solutions might exist to replace NPEs. A comprehensive analysis of all relevant alternatives and their 
safety profile is outside the scope of this case study. For the high volume uses restrictions have been 
successfully  implemented  with  relatively  low  cost  to  actors  in  the  supply  chains  since  there  are 
technically  feasible  alternatives  (ECHA  RAC  and  SEAC  2014a).  RAC  agreed  with  the  dossier 
submitter  (Sweden)  that  alcohol  ethoxylates,  glucose-based  surfactants  (alkyl  glucosides  and  alkyl 
glucamides), and alcanol fatty acid amines show lower toxicity, no indications of endocrine activity, 
and pose a lower level of environmental risk when used as alternatives for NPnEO as surfactants or 
emulsifiers  in  textile  processing.  Some  limitations  in  hazard  data  availability  for  these  alternatives 
was noticed.  

The authorisation applications received by the July 2019 deadline provide an overview of remaining 
uses, not explicitly banned in Annex XVII entry 46 and 46a185.  

185https://echa.europa.eu/applications-for-authorisation-previous-consultations. 

233 

 
 
 
 
 
 
                                                      
5  Comments on fitness check evaluation criteria 

Comments  on 
coherence 

 

In the context of the REACH restriction, the risk assessment applied a PNEC 
based  on  traditional,  apical  endpoints  not  related  to  endocrine  disruption  to 
demonstrate that risks are not controlled. For that reason, the Risk Assessment 
Committee  (RAC)  concluded  that  in  the  specific  case  (restriction  of  NP)  a 
conclusion on an ED based PNEC was not required.  

  RAC  discussed  approaches  setting  a  PNEC  for  endocrine  related  effects  but 
pointed  also  to  uncertainties  due  to  the  limited  knowledge  especially  for  taxa 
other than fish.   

  EQS values have been established (and are currently being reviewed) according 
to  the  Guidance  on  EQS  setting,  which  is  underpinned  by  the  concept  of  an 
overall threshold that protects all receptors and routes. Setting a threshold value 
is a practical requirement for monitoring and implementation of chemical water 
quality assessments for priority substances under the WFD. 

  The  study  determining  the  PNEC  in  the  2002  risk  assessment  report  and  the 
EQS (Kopf 1997 in EC 2005) in the 2005 EQS dossier (PNEC = EQS = 0.33 
μ/L),  a  72h  green  algae  study,  is  reported  in  the  2016  REACH  restriction 
dossier  with  a  different  endpoint  (EC10,growth  instead  of  EC10,biomass  vs).  The 
former value is 8-fold lower than the latter. According to ECHA Guidance on 
information  requirements  and  chemical  safety  assessment  (Chapter  7.b: 
Endpoint  specific  guidance)  algae  biomass  no  longer  is  considered  a  relevant 
endpoint, instead the preferred endpoint as regards algae is growth rate.  
The study determining the PNECfreshwater (0.6 ug/L) in the 2016 REACH Annex 
XV report, a 91-day study on rainbow trout (Brooke 1993 in ECHA 2013b) is 
not reported in the 2005 EQS dossier. A PNECaqua of 0.4 ug/L as chosen by the 
RAC as representative of marine and saltwater species (ECHA RAC and SEAC 
2014). A recent revision of the ecotox dossier of NP under the WFD has led to 
significantly  lower  proposed  EQS  (pending  ongoing  review  and  approval 
procedures).  

  Nonylphenol  and  nonylphenol  ethoxylates  have  been  thoroughly  assessed  for 
reproductive toxicity on the aquatic environment. They are widely restricted in 
Europe, with few speciality biomedical applications subject to authorisation. 
  The first regulatory intervention was triggered by assessments of reproductive 
toxicity. In the last years increasing scientific knowledge has led to updates of 
PNEC and EQS values underpinning risk assessments and their interpretation.  
  There  is  evidence  of  substantial  decrease  in  aquatic  exposure  of  NP  in  EU 
wastewater,  surface  waters  and  biota  in  the  last  two  decades.  Reduced 
concentrations of NP in the aquatic environment cannot be linked to changes in 
estrogenic activity of water bodies because this is mainly driven by more potent 
natural and synthetic estrogens. 

Comments  on 
effectiveness 

Comments  on 
efficiency 

  Monitoring  data  generated  under  the  WFD  have  been  successfully  used  to 
inform  environmental  exposure  assessment  in  ECHA  dossiers  (e.g.  2016 

234 

 
 
 
restriction report).  

  Despite  some  conceptual  differences  in  the  approaches  to  the  derivation  of 
PNECs for risk assessment of chemicals and EQS for water quality assessments 
are  similar.  The  two  processes  are  performed  separately  by  ECHA  and  by 
national  authorities in the context of the WFD. Resources could be optimised 
by greater coordination of assessments.  

235 

 
 
6  References 

Carvalho, R. N. et al. 2016. Monitoring-based exercise: second review of the priority substances list 
under 
Report. 
Framework  Directive. 
(https://circabc.europa.eu/w/browse/52c8d8d3-906c-48b5-a75e-53013702b20a).   

the  Water 

Science 

Policy 

JRC 

for 

ECHA  2012.  Member  State  Committee  Support  Document  for  Identification  of  4-Nonylphenol, 
branched  and  linear,  as  Substance  of  Very  High  Concern  because  due  to  their  endocrine  disrupting 
properties  they  cause  probable  serious  effects  to  the  environment  which  give  rise  to  an  equivalent 
those  of  CMRs  or  PBTs/vPvBs.  Adopted  on  13  December  2012. 
level  of  concern 
https://echa.europa.eu/documents/10162/d3c27f36-2704-597a-0b18-8e03d1a8e451 

to 

ECHA 2012. Registry of SVHC identification intention until outcome: 4-nonylphenol, branched and 
linear. https://echa.europa.eu/registry-of-svhc-intentions/-/dislist/details/0b0236e180e4ba35 

ECHA 2013a. Registry of SVHC identification intention until outcome 4-Nonylphenol, branched and 
linear, 
https://echa.europa.eu/it/registry-of-svhc-intentions/-
ethoxylated. 
/dislist/details/0b0236e180e4bc3d 

ECHA  2013b.  Registry  of  restriction  intention  until  outcome:  nonylphenol  and  nonylphenol 
ethoxylates. 
https://echa.europa.eu/registry-of-restriction-intentions/-
/dislist/details/0b0236e1806b0ddf 

ECHA 2019. Registry of SVHC intention until outcome by France. Tris(4-nonylphenyl, branched and 
linear)  phosphite  (TNPP)  with  ≥  0.1%  w/w  of  4-nonylphenol,  branched  and  linear  (NP).  
https://echa.europa.eu/registry-of-svhc-intentions/-/dislist/details/0b0236e1825f37c5 

ECHA  RAC  2017.  Risk-related  considerations  in  applications  for  authorisation  for  endocrine 
disrupting 
and  NPnEO. 
environment, 
https://echa.europa.eu/documents/10162/13637/npneo_and_opneo_for_agreement_final_en.pdf/ 

specifically  OPnEO 

substances 

the 

for 

ECHA  RAC  and  SEAC  2014a.  Opinion  on  the  Annex  XV  dossier  proposing  restrictions  on 
nonylphenol and nonylphenol ethoxylates. 

ECHA  RAC  and  SEAC  2014b.  Background  document  to  the  Opinion  on  the  Annex  XV  dossier 
proposing restrictions on nonylphenol and nonylphenol ethoxylates. 

Ecotox  Centre.  2016.  EQS  -  Vorschlag  des  Oekotoxzentrums  für:  4-Nonylphenol,  verzweigt  und 
linear.  

European  Commission  (EC).  2001.  Identification  of  priority  hazardous  substances.  Modified 
procedure  in accordance  with  Article  16(3)  of  the  Water  Framework  Directive.  Working  Document 
ENV/191000/01  of 
the  Commission  Services.  https://ec.europa.eu/environment/water/water-
dangersub/pdf/wd_env_191000_01_final.pdf 

European  Commission  (EC).  2002.  European  Union  Risk  Assessment  Report  4-nonylphenol 
(branched) and nonylphenol. 

European  Commission  (EC).  2005.  Common  Implementation  Strategy  for  the  Water  Framework 
Directive. Environmental Quality Standards (EQS). Substance data sheet: 4-Nonyplhenol (branched) 
and 
https://circabc.europa.eu/d/a/workspace/SpacesStore/af1b09f2-ff9a-46f6-ba2d-
d4bc2adfeee0/24_Nonylphenol_EQSdatasheet_310705.pdf  

nonylphenol. 

236 

 
 
 
European  Commission  (EC).  2011.  Common  Implementation  Strategy  for  the  Water  Framework 
Directive.  Guidance  document  No  27.  Technical  guidance  for  deriving  environmental  quality 
standards. 

European  Commission  (EC).  2016.  Report  from  the  Commission  to  the  European  Parliament,  the 
Council  and  the  European  Economic  and  Social  Committee  in  accordance  with  Article  138(7)  of 
REACH  to  review  if  the  scope  of  Article  60(3)  should  be  extended  to  substances  identified  under 
Article  57(f)  as  having  endocrine  disrupting  properties  with  an  equivalent  level  of  concern  to  other 
substances listed as substances of very high concern. COM(2016)814. 

European Commission (EC). 2016. Study on the Calculation of the Benefits of Chemicals Legislation 
on  Human  Health  and  the  Environment  Development  of  a  System  of  Indicators  Final  Report. 
doi:10.2779/034894 

European  Commission  (EC).  2020.  Common  Implementation  Strategy  for  the  Water  Framework 
Directive  -  WG  Chemicals  –  Sub-group  on  effect-based  methods.  Proposal  for  effect-based 
monitoring and assessment in the WFD (to be published soon). 

JRC 2020. Recommendation on the inclusion of effect-based methods for water quality assessments 
under the WFD (pending review by DG ENV) 

Klein  et  al.  1999.  Revised  proposal  for  a  list  of  priority  substances  in  the  context  of  the  Water 
Framework  Directive.  COMMPS 
https://ec.europa.eu/environment/water/water-
dangersub/pdf/commps_report.pdf. 

procedure. 

Lettieri,  T.  et  al.  2016.  Modelling-based  strategy  for  the  prioritisation  exercise  under  the  Water 
Framework Directive. JRC Science for Policy Report. https://circabc.europa.eu/w/browse/85b46283-
9353-4e67-bf56-e4d18b32cbaf. 

Miège, C., Gabet, V., Coquery, M., Karolak, S., Jugan, M.L., Oziol, L., Levi, Y., Chevreuil, M., 2009. 
Evaluation  of  estrogenic  disrupting  potency  in  aquatic  environments  and  urban  wastewaters  by 
combining chemical and biological analysis. TrAC Trends Anal. Chem. 28, 186–195. 

Rusconi M, Patrolecco L, Valsecchi S, Polesello S. 2015. Effectiveness of measures adopted for the 
reduction  of  nonylphenol  emissions  in  European  river  basins:  a  case  study  of  the  river  Lambro, 
Northern Italy. Water Policy 17(6): 1176-1190.  

Sumpter  JP,  Jobling  S.  2013.  The  occurrence,  causes  and  consequences  of  estrogens  in  the  aquatic 
environment. Environ Toxicol Chem 32: 249-251. 

Tusova  Z,  Vrana  B,  Smutna  M,  Novak  J,  Klucarova  V,  Grabic  R,  Slobodonik  J,  Giesy  JP, 
Hilscherova K. 2019 Analytical and bioanalytical assessments of organic micropollutants in the Bosna 
River  using  a  combination  of  passive  sampling,  bioassays  and  multi-residue  analysis.    Sci.  Tot. 
Environ. 659: 1599-1612. 

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