Endocrine Disruptors

Transcription

1 Endocrine Disruptors Dr. Bettina Hrdina-Zödl Institute for Plant Protection Products, Department of Toxicology Antragstellerkonferenz Vienna, Österreichische Agentur für Gesundheit und Ernährungssicherheit GmbH

2 Content Possible impact for Human Health Mechanisms of EDs Challenges for regulators Community Strategy for EDs (Long-term action: Horizontal regulation of EDs) Proposals for ED-criteria (definitions, development, working groups) Impact Assessment Threshold for EDs? AGES/ AT-activities Outlook Links 2

3 Possible Impact for Human Health Male and female reproduction Hormonal cancers Developmental neurotoxicity Metabolic syndrome Impairment of the neuroimmunesysteme Knowledge (Kortenkamp et al. State of the Art Assessment of EDs, 2011) 3

4 Mechanisms of EDs Binding to receptors and activation (agonistic effect) Binding to receptors and inactivation (antagonistic effect) Interference with transport of natural hormones (binding to transport proteins) Impairment of synthesis and breakdown rates of natural hormones 4

5 Challenges for Regulators Complexness of the hormonal system - Feed back processes - Expression of receptors Long window between exposure and effect Testing Guidances only for (anti) estrogens, (anti) androgens, thyroid hormones and steroidgenesis Quelle: WHO 2012: State of the Science of Endocrine Disrupting Chemicals 5

6 Community Strategy for EDs 11 actions - 7 short-term - 3 mediumterm - 1 long-term 4 Implementation Reports - COM (2011), 1001 (most recent) 6

7 Long-term Action: Horizontal Regulation of EDs REACH (1907/2006): SVHC (Authorisation) Water Framework Directive: List of pollutants in Annex VIII Biocide-Regulation (528/2012): Similar to PPP-Regulation Plant Protection Product Regulation (1107/2009): - Commission shall present specific scientific ED-criteria (by ) - Interim Criteria: Classification as R2/C2 or R2+ effects on endocrine organs - No approval if substance has ED properties that may cause adverse effect in humans or non-target organism, unless the exposure is negligible - Working group negligible exposure under Regulation 1107/2009 7

8 ED-Criteria (Definitions) Definitions: Endocrine Disruptor 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. (WHO/IPCS) Adversity A change in the morphology, physiology, growth, reproduction, development or lifespan of an organism, system or (sub)population that results in an impairment of functional capacity, an impairment of capacity to compensate for additional stress or an increase in susceptibility to other influences. (WHO/IPCS 2009) 8

9 ED-Proposals for Criteria (1) Until 2011: Summary see Kortenkamp-Report. ECETOC: UK/BfR: Bars et al. (2011) Science based guidance for the assessment of endocrine disrupting properties of chemicals. Regul Toxicol Pharmacol 59, ndocrine_disrupter_in_relation_to_potential_threat_to_human_ health.pdf Similarities: Potency Considerations 9

10 % Effect Potency ED effect within a certain concentration range Effect via ED mechanisms ED 30 No ED LOAEL Lowest-Observed-Adverse-Effect-Level No-Observed-Adverse-Effect-Level NOAEL 0 Effect via ED mechanisms Dose (mg/kg bw/day) 10

11 ED-Proposals for Criteria (2) DK: DK EPA (Danish Ministry of the Environment, Environmental Protection Agency) (2011) Establishment of criteria for endocrine disruptors and options for regulation. CHEMTRUST/WWF: WWF-EDC-Classification-Paper-Dec-2010.pdf Similarities: Categories for EDs 11

12 Working Groups for Criteria Lead DG ENV Expert Advisory Group on ED (EAG) - Established 2011 (2 nd Ad-hoc Meeting) - Provide detailed reflections on scientific issues relevant to endocrine disrupting substances EFSA- Working Group on Endocrine Active Substances - Established 2012 via DG SANCO - Scientific Opinion on 3 key questions (Scientific criteria to distinguish between EDs and other groups of chemicals with different modes of action, physiological modulation versus adverse effect, existing testing methods) Ad-hoc group of Commission Services, European Agencies and Member States under the Community Strategy for Endocrine Disruptors - Established 2010 via DG ENV - Interface between politics and science (Discussing horizontal aspects of regulation on endocrine disruptors) 12

13 ED-Proposal for Criteria (2 nd Vers. DG ENV) (February 2013) Identification of endocrine active substances based on a specific adverse effect caused by an endocrine mechanisms without potency considerations Categorisation via strenght of evidence (analogy to CMR substances) - Category 1: Endocrine disruptors - Category 2: Suspected endocrine disruptors - (Category 3: Potential endocrine disruptors ) 13

14 Impact Assessment Concerns were raised regarding plant protection products (e.g. management of pest resistances), therefore an impact assessment should be conducted by EU COM in the near future Road Map with definition of the problem, aims and options for impact assessment Different options regarding ED-criteria Impact studies (focus plant protection products and biocides, socioeconomic impact, trade, Cosmetic Regulation,?) Public consultation for impact assessment: 3 months When? 14

15 Threshold for EDs? REACH: : REACH review to extend the scope of Article 60 (3)- authorisation via socio-economic route - Is it possible to determine a threshold for EDs? - Delayed until mid 2014? Working groups - Ad-hoc group of Commission Services, European Agencies and Member States under the Community Strategy for Endocrine Disruptors - Expert Advisory Group on ED (EAG) 15

16 Editorial War in Scientific Community Pro Threshold - Editorial Food and Chemical Toxicology 2013: Scientifically unfounded precaution drives European Commission s recommendations on EDC regulation, while defying common sense, well-established science and risk assessment principles Contra Threshold - Berlaymont Declaration on Endocrine Disruptors Commentary in Environmental Health 2013: Science and policy on endocrine disrupters must not be mixed: a reply to a common sense intervention by toxicology journal editors Oct EU Commission (Assistant to the Chief Scientific Adviser): Meeting of scientists from groups above on Endocrine Disruptors (discussion ongoing) 16

17 AGES/AT- Activities Lead for development of ED-criteria: BMLFUW (Environmental Section) Co-work between AGES, BMLFUW, BMG and UBA - Internal meetings - Stakeholder presentations AGES Task Force (lead DSR): Plant protection products, food contact materials, cosmetics, pharmaceuticals, medical devices, drinking water, toys,. 17

18 Outlook Impact assessment regarding ED-criteria with 3 months public consultation (Meeting of Ad hoc group for 2014 foreseen) Guidance Document for Interim Criteria: R2+ effects on endocrine organs (Biocide-Regulation, DG ENV) Guidance Document for application of ED-criteria Workshop for further development of testing methods (prioritisation) ECHA ED expert group for REACH and biocides; in the future also for plant protection products? Revision Community Strategy for EDs 18

19 Links Kortenkamp et al.: State of the Art Assessment of Endocrine Disruptors (2011): inal_report.pdf Report of the Endocrine Disrupters Expert Advisory Group: Key scientific issues relevant to the identification and characterisation of endocrine disrupting substances: EFSA (Scientific Opinion on the hazard assessment of endocrine disruptors: Scientific criteria for identification of endocrine disruptors and appropriateness of existing test methods for assessing effects mediated by these substances on human health and the environment): 19