Thresholds for Endocrine Disrupters and Related Uncertainties

The European Commission, under Directorate-General for Environment (DG ENV) created an ad hoc group of Commission Services and Member States to serve the EU Community Strategy on Endocrine Disrupters. The ad hoc group created the Endocrine Disrupters Expert Advisory Group (ED EAG) in November 2011 to provide detailed reflections on scientific issues relevant to identifying and assessing endocrine disrupting substances, not specific to any regulatory framework. The European Commission's Joint Research Centre was tasked with facilitating and chairing meetings of the ED EAG and preparing this report. The scope of the present report is to capture the experts' opinions on scientific issues relevant to the likelihood of the existence of thresholds for a biological response of an organism to an ED, in particular considering thresholds of adversity and the uncertainties associated with reliably estimating such thresholds from experimental data. The question although relevant to the evaluation of EDs per se was specifically raised by the ad hoc group in relation to a review of the REACH regulation with respect to treatment of EDs under authorisation (Article 138 (7)).JRC.I.5-Systems Toxicolog

Key scientific issues relevant to the identification and characterisation of endocrine disrupting substances - Report of the Endocrine Disrupters Expert Advisory Group

The European Commission, under Directorate-General for Environment (DG ENV) as file leader of the Community Strategy on Endocrine Disrupters, In 2010, DG ENV created an ad hoc group of Commission Services and Member States on the EU Community Strategy on Endocrine Disrupters. The ad hoc group created the Endocrine Disrupters Expert Advisory Group (ED EAG) in November 2011 to provide scientific advice on the development of criteria for identification of EDs. The European Commission's Joint Research Centre was tasked with running the expert sub-group, consisting of around 40 experts nominated by Member State regulatory authorities, relevant industry associations and non-governmental consumer/environmental protection organisations. This report captures the experts' opinions on key scientific issues relevant to the identification and characterisation of endocrine disrupting substances (EDs). It provides one input to the Commission’s decisions on the establishment of horizontal criteria for the identification of EDs to be applied as appropriate across all relevant pieces of legislation concerning the control and risk management of chemicals substances (including pesticides, biocides, pharmaceuticals, industrial chemicals, controls on water quality, occupational exposure, etc).JRC.I.5-Systems Toxicolog

Expert survey on identification of gaps in available test methods for evaluation of endocrine disruptors

According to the 2012 WHO/UNEP publication 'State of the Science of Endocrine Disrupting Chemicals' research into endocrine disrupting chemicals over the last decade has indicated that, despite the progress achieved in development and validation of test methods for evaluation of endocrine disruptors, there are still several gaps that need to be addressed. Considering the expected significant amount of work needed to fill the gaps and the limited resources available, it will be important to set priorities for the upcoming period (next 5-10 years) for the development and validation of test methods. Thus there is a need to focus the European input to the OECD test guideline programme to effectively enhance the identification of chemical substances with endocrine disrupting properties whilst making best use of existing resources. With this objective in mind, DG Environment, supported by JRC, is organising a European expert workshop on setting priorities for further development and validation of test methods for evaluating endocrine disruption. The workshop will take place on 30 May - 01 June 2017 in Brussels. The deliberations will focus on what is necessary and achievable in the context of resources, timescales and animal welfare considerations. In preparation for the workshop, JRC has drawn up a questionnaire to gather input from experts in the field on key issues to be used as a basis for the further discussions at the workshop. An online survey with the title "Identifying gaps in available test methods for evaluation of endocrine disruptors" was performed on the EU Survey platform and open for commenting from 19/05/2015 until 15/06/2015. A selected group of experts (EFSA Scientific Committee and WG on EDs, ECHA ED WG and RAC, WNT (European members from OECD webpage), Experts identified in Annex 3 of the "Roadmap for setting priorities for further development and validation of test methods and testing approaches for evaluating endocrine disruptors") was invited to participate in the survey. Experts were asked to rank endocrine related diseases/disorders regarding the possibility to predict them with existing test methods (TMs). They were further asked to rank diseases/disorders regarding the need to develop new test methods to better cover those. Experts were then requested to provide their views on including further tests based on those discussed in the OECD (2012) "Detailed Review Paper on the state of the science on novel in vitro and in vivo screening and testing methods and endpoints for evaluating endocrine disruptors" and their views on the current OECD Conceptual Framework and proposals for improvements. Forty experts representing 15 countries and different stakeholder groups (authorities; academia; civil society organisation; industry) replied. The purpose of this report is to present the detailed survey results. Multiple choice questions were evaluated and where possible quantitative rankings were performed. In addition, the survey respondents provided a lot of valuable information in numerous free text comments. Those are included in the report in tables as they were received, without editing them, unless personal information had to be removed. Brief summaries of the main points raised are added after each section.JRC.F.3-Chemicals Safety and Alternative Method

Description of Prototype Modes-of-Action Related to Repeated Dose Toxicity

This report presents the definition and detailed documentation of chosen toxicological MoAs associated with repeated dose target organ toxicity as a first step in building a "prototype" safety assessment framework. In addition to providing a detailed description of the two chosen MoAs related to chronic liver toxicity, namely "MoA from Protein Alkylation to Liver Fibrosis" and "MoA from Liver X Receptor Activation to Liver Steatosis", the report also describes the working process leading to this result including the problems that have been encountered. The exercise followed as far as possible relevant WHO-IPCS and OECD guidance. The report represents the first deliverable of a contract of work between Cosmetics Europe and the European Commission's Joint Research Centre for supplementing the work of the SEURAT-1 research cluster.JRC.I.5-Systems Toxicolog

Strategic aims for improving the regulatory assessment of Developmental Neurotoxicity (DNT) using non-animal methods

Currently, the identification of chemicals that have the potential to induce developmental neurotoxicity (DNT) is based on animal testing, since there are no regulatory accepted alternative methods for this purpose. Since at the regulatory level, systematic testing of DNT is not a standard requirement within the EU legislation of chemical safety assessment, DNT testing is only performed in higher tiered tests triggered based on structure activity relationships or evidence of neurotoxicity in systemic adult studies. However, these triggers are rarely used and in addition do not always serve as reliable indicators of DNT as they are observed in an adult rodent animal. Consequently, to date only a limited amount of chemicals (Grandjean and Landrigan, 2006; Smirnova et al., 2014), mainly pesticides (Bjørling-Poulsen et al., 2008) have been tested under US EPA (OPPTS 870.630) or OECD DNT TG 426. Therefore, there is the pressing need for developing alternative methodologies that can more rapidly and cost-effectively screen large numbers of chemicals for their potential to cause DNT. In this report we propose that in vitro studies could contribute to the identification of potential triggers for DNT evaluation since existing cellular models permit the evaluation of a chemical impact on key neurodevelopmental processes, mimicking different windows of human brain development, especially if human models derived from induced pluripotent stem cells are applied. Furthermore, the battery of currently available DNT alternative test methods anchored to critical neurodevelopmental processes and key events identified in DNT Adverse Outcome Pathways (AOPs) could be applied to generate in vitro data useful for various regulatory purposes. Incorporation of in vitro mechanistic information would increase scientific confidence in decision making, by decreasing uncertainty and leading to refinement of chemical grouping according to biological activity. In this report development of IATA (Integrated Approaches to Testing and Assessment) based on key neurodevelopmental processes and AOP-informed is proposed as a tool for not only speeding up chemical screening, but also providing mechanistic data in support of hazard assessment and in the evaluation of chemical mixtures. Such mechanistically informed IATA for DNT evaluation could be developed integrating various sources of information (e.g., non-testing methods, in vitro approaches, as well as in vivo animal and human data), contributing to screening for prioritization, hazard identification and characterization, and possibly safety assessment of chemicals, speeding up the evaluation of thousands of compounds present in industrial, agricultural and consumer products that lack safety data on DNT potential. It is planned that the data and knowledge generated from such testing will be fed into the development of an OECD guidance document on alternative approaches to DNT testing.JRC.F.3-Chemicals Safety and Alternative Method

Alternative Approaches Can Reduce the Use of Test Animals under REACH.

Abstract not availableJRC.I-Institute for Health and Consumer Protection (Ispra

The Adverse Outcome Pathway approach in nanotoxicology

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Targeted Stakeholder Consultation in the context of a Fitness Check of the EU legislation with regard to Endocrine Disruptors - Factual Summary Report

Under the European Commission's Better Regulation initiative the JRC is leading a Fitness Check of the EU legislation for the identification and control of endocrine disrupting substances. Stakeholder consultation is an important part of any Fitness Check. This report provides a brief factual overview of the responses received over an 8 week period from 06/12/19 to 31/01/20 to over 30 questions addressed to stakeholder organisations such as businesses, public authorities, academia, research organisations, or civil society organisations. The aims of the consultation were to collect views on effectiveness, efficiencies and possible legislative incoherencies of EU legislation with respect to EDs and possible impacts on stakeholders. Two other types of consultations conducted under this Fitness Check, one focused on citizens and the other on small and medium-sized enterprises will be reported separately. Responses will provide an essential input to the Fitness Check analysis carried out by the JRC. A more detailed analysis of the responses to each of consultations will be published in a synopsis report along with Fitness Check evaluation at the end of the process.JRC.F.3-Chemicals Safety and Alternative Method

Review On Production Processes Of Decabromodiphenyl Ether (DECABDE) Used In Polymeric Applications In Electrical And Electronic Equipment, And Assessment Of The Availability Of Potential Alternatives To DECABDE

In this study commissioned by DG ENV, the JRC-IHCP-ECB has reviewed the production processes of DecaBDE, in particular its NonaBDE content, and explored the availability of potential DecaBDE alternatives used in polymeric applications for EEE (cost of substitution and recyclability of alternatives was outside the scope of the study).JRC.I.3-Toxicology and chemical substance