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 1.1 Background to the Fitness Check 1.2 Objectives of the Fitness Check 2 METHODOLOGY 2.1 Scope of the Fitness Check 2.2 Fitness Check questions and baseline 2.3 Mapping of of regulatory provisions and review of key documents 2.4 Case studies 2.5 Consultation activities 3 STATE OF PLAY 4 COHERENCE 4.1 Data requirements 4.2 Hazard identification 4.3 Risk assessment 4.4 Risk management 4.5 Coherence with non-EU jurisdictions 5 EFFECTIVENESS

5.1 Current process of ED identification 5.2 Biocidal Products and Plant Protection Products Regulations 5.3 REACH 5.4 Other sector-specific and product-specific legislation 5.5 Communication 5.6 Monitoring data 5.7 Human health and environmental impact evidence and indicators 5.8 Market surveillance 5.9 Functioning of the internal market, competitiveness and innovation 6 EFFICIENCY 7 RELEVANCE 7.1 Relevance to citizens and stakeholders 7.2 Ability to adapt to the evolving societal and economic context 7.3 Ability to adapt to scientific progress 8 EU ADDED VALUE 8.1 Joining forces and efficient use of resources 8.2 Preserving the functioning of the single market 8.3 Legislative measures alignment between Europe and global regimen 9 CONCLUSIONS 10 REFERENCES

11 GLOSSARY Annex 1. Procedural information 1 Lead DG and internal references 2 Organisation and timing 3 Exceptions to the better regulation guidelines 4 Consultation of the Regulatory Scrutiny Board 5 Evidence, sources and quality Annex 2. Synopsis report: stakeholder consultation activities 1 Summary 2 Introduction and approach 3 Stakeholder groups covered by the consultation activities 4 Outcome of the public consultation 4.1 Respondents 4.2 How well informed do citizens feel? 4.3 Public views on effectiveness 4.4 Public views on efficiency 4.5 Summary of public views on regulatory testing and animal welfare 4.6 Public views on EU-added value 4.7 Public views on relevance 4.8 Additional comments made by citizens

5 Outcome of the stakeholder consultation 5.1 Structure of survey 5.2 Respondents 5.3 Familiarity of stakeholders with relevant legislation 5.4 Stakeholder views on coherence (overall statistics) 5.5 Stakeholder views on effectiveness (overall statistics) 5.6 Stakeholder views on efficiency (overall statistics) 5.7 Stakeholder views on relevance (overall statistics) 5.8 Stakeholder views on EU-added value (overall statistics) 5.9 Breakdown of stakeholder views according to stakeholder group 6 Outcome of the SME consultation 6.1 Respondents 6.2 Legislation affecting respondents 6.3 Information in the company about endocrine disruptors 6.4 SME views on coherence 6.5 SME views on effectiveness 6.6 SME views on efficiency 6.7 SME views on EU added value 6.8 Additional comments made by SMEs Annex 3. Methodology

1 Summary 2 Workflow 3 Preliminary analysis of current situation 3.1 Questionnaire to policy DGs 3.2 Identification of Regulatory Reviews/Better Regulation activities 3.3 Definition of scope 3.4 Formulation of Fitness Check questions 4 Extraction and review of available evidence 4.1 Mapping of provisions 4.2 Policy and scientific sources of evidence 4.3 Evidence base and limitations 4.4 Case studies 4.5 Evidence base and limitations 4.6 Economic case studies 5 Consultation activities 5.1 External consultation activities 5.2 Evidence base and limitations Annex 4. Mapping of provisions and regulatory processes for identifying and managing Endocrine Disruptors 1 Biocidal Products 2 Plant Protection Products and residues

3 REACH 4 Classification, Labelling and Packaging (CLP) 5 POPs Regulation 6 Toys 7 Food legislation 7.1 Food Contact Materials 7.2 Contaminants in feed and food 7.3 Food additives 8 Cosmetic Products 9 Medical devices and in vitro diagnostics 10 Human and veterinary medicines 11 Occupational Safety and Health legislation (OSH) 12 Water 13 Chemical-product-waste interface 14 Other in-scope legislation 14.1 Detergents 14.2 Fertilising Products 14.3 Ecolabel Regulation 14.4 General Product Safety Directive 14.5 Seveso III Directive and Industrial Emission Directive

14.6 Directive on air quality 14.7 WTO rules 15 References 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 2 Substance profile 2.1 Exposure pathways of concern 2.2 Effects on human health and the environment 3 3-BC and structurally similar UV filters in EU legislation 3.1 Regulating 3-BC in cosmetics legislation 3.2 Regulating 3-BC under REACH 3.3 Status of structurally similar UV filters 4 Comments on fitness check evaluation criteria 5 References 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 2 Substance profile 2.1 Exposure pathways of concern 2.2 Hazard endpoints of concern 3 DEHP and other phthalates in EU legislation

3.1 Regulating phthalates under REACH and preceding legislation 3.2 Enforcement of regulatory measures under REACH 3.3 Regulating phthalates under food contact materials (FCM) 3.4 Regulating DEHP in cosmetics 3.5 Regulating DEHP in medical devices 3.6 Regulating DEHP at the interface of chemical and waste legislation 3.7 Regulating DEHP under the Water Framework Directive 4 Impact of regulation 4.1 Decline in use and exposure 4.2 Shift to alternatives 5 Comments on fitness check evaluation criteria 6 References Annex 5C. Case Study: nonylphenol 1 Case study factsheet: overview of concerns for human health and environment and main regulatory intervention 2 Substance profile 2.1 Exposure pathways of concern 2.2 Effects on human health and the environment 3 Regulating nonylphenols in EU legislation 3.1 Regulating nonylphenols in REACH 3.2 Regulating nonylphenols under other chemical legislation

3.3 Regulating nonylphenols under the Water Framework Directive 4 Impact of regulation 4.1 Reduced exposure 4.2 Shift to alternatives 5 Comments on fitness check evaluation criteria 6 References



ABBREVIATIONS Abbreviation Explanation 3-BC 3-Benzylidene camphor AOP Adverse Outcome Pathway AR Androgen Receptor BAT Best Available Techniques BBP Benzyl Butyl Phthalate BCF Bioconcentration Factor BREF BAT reference documents BPA Bisphenol A BPR Biocidal Products Regulation CA Competent Authority CF Conceptual Framework (OECD Conceptual Framework for Testing and Assessment of Endocrine Disrupters) CLP Classification, Labelling and Packaging CMR Carcinogenic, Mutagenic or toxic for Reproduction CPR Cosmetic Products Regulation DBP Dibutyl phthalate DEHP Diethylhexyl phthalate DIBP Diisobutyl phthalate DNT Developmental neurotoxicity DWD Drinking Water Directive EAS Endocrine Active Substance EATS Estrogen, Androgen, Thyroid, Steroidogenic EC European Commission ECHA European Chemicals Agency ED Endocrine Disruptor EFSA European Food Safety Authority ELoC Equivalent Level of Concern EOGRTS Extended-One-Generation Reproductive Toxicity Study EQS Environmental Quality Standard ER Estrogen Receptor ESAC ECVAM Scientific Advisory Committee EURL ECVAM European Union Reference Laboratory for alternatives to animal testing FAO Food and Agriculture Organization FC Fitness Check FCM Food Contact Material GD Guidance document GPSD General Product Safety Directive IATA Integrated Approach(es) to Testing and Assessment ICH International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use IPCS International Programme on Chemical Safety IVDR In Vitro Diagnostics Regulation JRC Joint Research Centre LMWP Low Molecular Weight Phthalates LOAEL Lowest observed adverse effect level LOEC Lowest observed effect concentration MDR Medical Devices Regulation MoA Mode of Action MRL Maximum Residue Level MSC Member State Committee MS Member State NAM New Approach Methodology NGO Non Governmental Organisation NGRA Next Generation Risk Assessment NOEC No Observed Effect Concentration NP Nonylphenol OECD Organisation for Economic Cooperation and Development OML Overall Migration Limit OSH Occupational Safety and Health legislation PBT Persistent, Bioaccumulative and Toxic PCB Polychlorinated biphenyl PEC Predicted Environmental Concentration PHS Priority Hazardous Substance PFAS Per- and polyfluoroalkyl substances PNEC Predicted No Effect Concentration POP Persistent Organic Pollutant PPP Plant Protection Product PPPR Plant Protection Products Regulation PS Priority Substance RAC (ECHA) Risk Assessment Committee REACH Registration, Evaluation, Authorisation and Restriction of Chemicals RoHS Restriction of Hazardous Substances SEAC (ECHA) Socio-Economic Analysis Committee SCCP Scientific Committee on Consumer Products (replaced by the SCCS) 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 Small and Medium-sized Enterprise SML Specific Migration Limit SPS (Agreement on the Application of) Sanitary and Phytosanitary Measures SVHC Substance of Very High Concern TG Test Guideline TBT (Agreement on) Technical Barriers to Trade TDI Tolerable Daily Intake UNEP United Nations Environment Programme UN GHS United Nations Globally Harmonised System UWWD Urban Waste Water Directive VICH International Cooperation on Harmonisation of Technical Requirements for Registration of Veterinary Medicinal Products vPvB very Persistent and very Bioaccumulative WFD Water Framework Directive WHO World Health Organization WoE Weight of Evidence WTO World Trade Organization



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.

1.1Background to the Fitness Check 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 Disruptors. 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) Regulation), have been banned or restricted on the basis of these adverse effects. 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 approach (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 products and biocidal products. 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 criteria. The criteria are based on the 2002 IPCS/WHO definition (IPCS, 2002), according to which 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”. 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 products . 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 health. 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.



Name and abbreviation CAS no. Effects Legislation 2,2-dibromo-2-cyanoacetamide 10222-01-2 Human Health and Environment BPR Cyanamide 420-04-2 Human health and Environment BPR Cholecalciferol 67-97-0 Human Health and Environment BPR 3-benzylidene camphor 15087-24-8 Environment REACH 4-(1,1,3,3-tetramethylbutyl)phenol 140-66-9 Environment REACH 4-(1,1,3,3-tetramethylbutyl)phenol, ethoxylated N/A Environment REACH 4-heptylphenol, branched and linear N/A Environment REACH 4-Nonylphenol, branched and linear N/A Environment REACH 4-Nonylphenol, branched and linear, ethoxylated N/A Environment REACH 4-tert-butylphenol 98-54-4 Environment REACH Benzyl butyl phthalate (BBP) 85-68-7 Human Health REACH Bis(2-ethylhexyl) phthalate (DEHP) 117-81-7 Human Health and Environment REACH Bisphenol A 80-05-7 Human Health and Environment REACH Butyl 4-hydroxybenzoate 94-26-8 Human Health REACH Dibutyl phthalate (DBP) 84-74-2 Human Health REACH Dicyclohexyl phthalate (DCHP) 84-61-7 Human Health REACH Diisobutyl phthalate 84-69-5 Human Health REACH p-(1,1-dimethylpropyl)phenol 80-46-6 Environment REACH 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 N/A Environment REACH Tris(4-nonylphenyl, branched and linear) phosphite (TNPP) with ≥ 0.1% w/w of 4-nonylphenol, branched and linear (4-NP) 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. 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”, 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. 1.2Objectives 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 EDs, 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.

2METHODOLOGY ·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. 2.1Scope 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. 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 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 2.2Fitness 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. 2.3Mapping 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. 2.4Case 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).

2.5Consultation activities 2.5.1External 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.



3STATE 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. 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 (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 legislation (more details are given in Annex 4). 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) No 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 Yes Criteria for ED identification introduced in 2018. ED-specific and generic risk approach with limited options for derogation (negligible exposure and essential use). Criteria for ED identification are in essence the same as for the Biocidal Products Regulation. Co-formulants in plant protection products have to be registered under REACH. Maximum Residue Levels of Pesticides Regulation (EC) No 396/2005 Protection of consumers from unacceptable risk to pesticide residues in food and feed of plant and animal origin by: ·determining maximum levels of pesticide residues No Specific risk approach Hazard identification is covered under the Plant Protection Products Regulation. Biocidal Products Regulation (EU) No 528/2012 Protection of human and animal health and the environment from exposure to hazardous chemicals in biocidal products by: ·regulating the approval of active substances which may be used in biocidal products regulating the authorisation for placing on the market and use of biocidal products Yes. 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). Criteria for ED identification are in essence the same as for the Plant Protection Products Regulation. Co-formulants in biocidal products have to be registered under REACH. REACH Regulation (EC) No 1907/2006 Protects the public (citizens, workers, consumers) and the environment from exposure to hazardous chemicals, while promoting alternative methods for assessment of hazards of substances by: ·regulating the placing on the market of chemicals (on its own, in mixtures or from articles) through registrations, authorisation and restrictions ·communication of hazards, risks and safe use conditions throughout supply chain Yes, identification of ED as Substances of Very High Concern (SVHCs) possible through Art 57 (f). Registration obligations require industry to assess hazards of substances. Data requirements depend on tonnage14. Assessment of endocrine disrupting properties through substance evaluation, SHVC-identification and as part of restrictions. EDs are listed as SVHCs if meeting the “Equivalent Level of Concern” criteria. SVHC listing (generic risk approach) triggers notification provisions. SVHCs are regulated through authorisation and restrictions through specific risk approaches and risk-benefit approaches. Restrictions can be based on endocrine disrupting properties if they lead to an unacceptable risk. Registrants have to ensure that risks from manufacturing or use of chemicals are controlled or that emissions are minimised. Hazard properties including endocrine disrupting properties have to be reported via safety data sheets to ensure safe use throughout the supply chain. Several provisions under REACH (e.g. on registration, authorisation, restriction) apply also to chemicals regulated under sector- or product-related legislation, unless explicitly excluded under REACH. CLP: Classification, Labelling and Packaging of substances and mixtures (EC) No 1272/2008 Protects human health and the environment by: ·harmonised hazard classification as cross-cutting trigger for risk assessment and/or management in other legislation ·harmonised labelling and packaging requirements ensuring hazard communication along supply chain No Endocrine disrupting properties are covered if they lead to a substance fulfilling the criteria of other hazard classes (carcinogenic, toxic tor reproduction, specific target organ toxicity – repeated exposure, etc). Hazard-based. Classification of substances as Carcinogenic, Mutagenic or toxic for the Reproduction (CMR) and other hazard classes triggers hazard communication (labelling, packaging). CLP classification triggers provisions under many pieces of legislation. 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 No Criteria for Persistent Organic Pollutants (POPs) do not specifically address endocrine disrupting properties, although they can be taken into account for the T-criterion (toxicity). The identification as POPs is mainly a generic risk approach and triggers ban and/or restrictions. Exemptions can be introduced based on risk-benefit considerations. Food contact materials legislation – Regulation (EC) No 1935/2004 Protects consumers and animals (feed Directive) from exposure to hazardous substances in food by: ·setting rules on the composition of food contact materials, mainly for plastics, including an authorised list of substances and restrictions No Endocrine disrupting properties are taken into account as other hazards in risk assessment Risk management of hazardous substances (authorisations, maximum levels), is mainly a specific risk approach. Substances used in food contact materials have to comply with REACH registration provisions. Substances identified as SVHCs with endocrine disrupting properties with effects on the environment are subject to REACH authorisation provisions. Substances with endocrine disrupting properties with effects on human health or the environment can be restricted under REACH. Contaminants in food Regulation 315/93/EEC and in animal feed Directive 2002/32/EC ·establishing maximum levels or maximum tolerances for certain contaminants in food and animal feed Food Additives and food enzymes and food flavourings, Regulation (EC) No 1333/2008 and Regulation (EC) No 1331/2008 ·establishing a common authorisation procedure for food additives, food enzymes and food flavourings by including also data required for safety assessment Cosmetic Products Regulation (EC) No 1223/2009 Protects consumers from exposure to hazardous chemicals in cosmetic products by regulating the placing on the market through two main channels: ·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. No Endocrine disrupting properties are taken 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. Substances used in cosmetic products have to be registered under REACH. Substances identified as SVHCs with endocrine disrupting properties with effects on the environment are subject to REACH authorisation provisions and can be restricted under REACH. Regulation (EU) 2017/745 on medical devices Protects patient users and, where appropriate, other persons from exposure to hazardous chemicals in medical devices by: ·setting general safety and performance requirements for medical devices and in vitro diagnostics ·ensuring that the relevant scientific opinions of the relevant scientific committees are taken into account No Hazards from endocrine disrupting properties are taken into account in risk assessments. Presence of EDs must be justified and approvals are based on risk-benefit. ED identification refers to REACH and (for medical devices only) to Biocidal Products Regulation. Substances used in medical devices have to be registered under REACH. Substances identified as SVHCs with endocrine disrupting properties with effects on the environment are subject to REACH authorisation provisions. Substances with endocrine properties with effects on human health or the environment can be restricted under REACH. Regulation (EU) 2017/746 on in vitro diagnostic medical devices Toy Safety Directive 2009/48/EC Protects children from the exposure to hazardous chemicals in toys by: ·prohibiting the use of substances which are Carcinogenic, Mutagenic or toxic for the Reproduction (CMR) with limited possibilities for derogation ·establishing specific limit values for any chemical (including identified EDs) in toys for children under 36 months of age and for toys intended to be placed in the mouth No Hazards from endocrine disrupting properties are taken into account as other hazards. Combination of generic risk (CMRs are banned in principle) and specific risk approaches (limit values). All substances used in toys have to comply with provisions under REACH. Provisions for registration, authorisations and restrictions apply. Fertilising Products Regulation (EU) 2019/1009 Protects human, animal and plant health, safety and the environment by: ·regulating the placing on the market of chemicals in fertilising products No Hazards from endocrine disrupting properties are taken into account as other hazards. Specific risk approach All substances used in fertilising products have to comply with provisions under REACH. Provisions for registration, authorisations and restrictions apply. Detergents Regulation (648/2004/EC) Achieves the free movement of detergents while, at the same time, ensuring a high degree of protection of the environment and human health by: ·regulating the placing on the market of surfactants in detergents based on biodegradability standards and phosphorus content ·labelling detergents No Not applicable Not applicable Substances used in detergents are also regulated via REACH, Biocidal Products Regulation and the Cosmetic Products Regulation. Provisions under those regulations apply. Medicinal products for humans (Directive 2001/83/CE) 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: ·requiring environmental risk assessment and risk mitigation measures for endocrine active substances No Risk-benefit approach. The outcome of the environmental risk assessment does not influence the approval of human medicines but can trigger measures to minimise exposure (e.g. communication, monitoring). Regulation (EU) 2019/6 on veterinary medicinal products15 Main emphasis on the therapeutic benefit for the target group evaluated in the context of possible adverse side effects and risks to target organisms (treated animals). Evaluates and minimises the unintended effects of veterinary medicinal products via the environment by: ·requiring environmental risk assessment and establishing approval procedures considering environmental risks No Endocrine disrupting properties not specifically addressed. Risk-benefit approach. 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. General Product Safety Directive (2001/95/EC) Protects consumers health and safety by requiring that only safe products are placed on the market: ·rapid exchange of information between member states on measures taken against unsafe 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. Does not include provisions for hazard identification. Identified EDs are included in market surveillance activities based on 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 and generic risk assessment. Water Framework Directive (2000/60/EC) Water legislation collectively aims at protecting and enhancing water resources to achieve good water quality. This includes the good chemical and ecological status of European surface waters, the good chemical and quantitative status of groundwater and the good environmental status of marine waters. It does this by: ·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 Yes, given the obligation to identify priority (hazardous) substances under the Water Framework Directive (WFD) (including substances that are toxic, persistent and liable to bio-accumulate and “substances of equivalent concern”), and the inclusion of endocrine disrupting substances in the indicative list of main pollutants. The assessment of endocrine disrupting properties of candidate priority (hazardous) substances takes assessments under other legislation into account, if available. When necessary (e.g. for substances in waste or transformation products) assessments are carried out considering evidence regarding the intrinsic hazard of the substance concerned. 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. This is the case for priority substances and priority hazardous substances under the WFD and for substances representative of endocrine disrupting effects under the Drinking Water Directive. The identification of priority (hazardous) substances considers the selection of substances of concern undertaken in the relevant legislation regarding hazardous substances (e.g. REACH or PPPR or BPR) or relevant international agreements Priority substances Directive (39/2013/EC) 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 at Work (98/24/EC) Protect safety and health of workers from risks arising, or likely to arise, from the effects of hazardous substances at work by: ·taking preventing measures and proposing indicative and/or binding occupational exposure limit values ·encouraging all necessary measures to adjust temporally the working conditions of pregnant, recently given birth or breastfeeding workers ·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. No Hazards from endocrine disrupting properties are taken into account as other hazards. Non ED-specific. Combination of generic and specific risk approaches, following a hierarchy of measures going from preventing exposure to reducing it to the lowest level technically possible for hazardous chemicals such as carcinogens, mutagens or reprotoxicants. Refers to Classification Labelling and Packaging (CLP) hazard classes for hazard identification. Carcinogens and Mutagens at Work Directive (2004/37/EC) Pregnant Workers Directive (92/85/EEC) Young People at Work Directive (94/33/EC) Directive 2008/98/EC on waste Protection of human health and the environment against harmful effects caused by waste by: ·establishing rules 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 Generic risk approach. Management of waste including hazardous substances is done through classification of hazardous waste. Notification of hazardous substances in material streams based on REACH listing of Substances of Very High Concern (including SVHCs with endocrine disrupting properties). Notification of SVHCs in articles indirectly takes into account endocrine disrupting properties to the extent a substance has been identified as SVHC under REACH. Definition of hazardous waste refers to Classification Labelling and Packaging (CLP) hazard classes. Restriction of the use of certain hazardous substances in electrical and electronic equipment (Directive 2011/65/EU) Contributes to the protection of human health and the environment through environmentally sound recovery and disposal of waste electrical and electronic equipment by: ·restricting the use of certain hazardous substances No Not applicable Specific risk approach. Risk-benefit considerations apply. Substances to be regulated are identified based on their negative impact on waste treatment and recycling, potential for environmental and worker exposure and replacement options. Substances identified as SVHCs with endocrine disrupting properties and which have been added to the REACH authorisation list, as well as substances that are restricted under REACH can be considered for restrictions under RoHS. Industrial emissions (integrated pollution prevention and control) Directive (2010/75/EU) Aims at environmental protection and improvement of environmental quality by: ·setting rules to prevent or to reduce emissions into air, water and land and to prevent the generation of waste ·requiring the application of Best Available Techniques (BAT) in installations. No. Does not include provisions for hazard identification. Not applicable Emission limit values set in this directive are based on the BAT, not on (eco)toxicity criteria. Seveso-III-Directive (2012/18/EU) Protection of human health and the environment by: ·setting rules to prevent major-accidents involving dangerous substances ·provisions to limit the consequences of such accidents No. Defines "dangerous substances" based on certain Classification Labelling and Packaging (CLP) hazard classes and volume. Not applicable Mainly generic risk approach with consideration of potential exposure. Directive 2008/50/EC on ambient air quality and cleaner air for Europe; Directive 2004/107/EC relating to arsenic, cadmium, mercury, nickel and polycyclic aromatic hydrocarbons in ambient air. Protection of human health and the environment by: ·monitoring air quality against established air quality standards (i.e. maximum allowed concentrations) ·taking measures to ensure compliance No Not applicable The determination of quality standards follows a specific risk approach. Ecolabel is not awarded to goods containing inter alia substances identified under REACH as SVHCs with endocrine disrupting properties. Regulation (EC) No 66/2010 on the EU Ecolabel Promotes products and services meeting high environmental standards throughout their life-cycle by: ·implementing a voluntary labelling scheme (ecolabel) No Not applicable The Ecolabel criteria are based on hazards (generic risk approach). Ecolabel is not awarded to goods containing inter alia substances identified under REACH as SVHCs with ED properties.



4COHERENCE ·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 toxicity 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 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 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)? 4.1Data 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. 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”. 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, cosmeticspharmaceuticals. 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 cosmeticsrefer 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. 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) No 283/2013 and (EU) No 284/2013, respectively, and the accompanying Commission 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 2. 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 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. 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 developmental toxicity. Many recent SCCS opinions have relied 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). 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 2019 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 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. 4.2Hazard identification 4.2.1Identification 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). 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 improvements. The Agencies are also collaborating on ED assessments for specific substances of common interest. 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.

4.2.2Identification 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 (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 recognised 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.

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