The OECD Test Guidelines Programme develop Test Guidelines and other tools to support countries’ needs related to testing and assessment of chemicals for endocrine disrupters.
The OECD releases the Revised Guidance Document 150 on Standardised Test Guidelines for Evaluating Chemicals for Endocrine Disruption originally published in 2012 and updated in 2018 to reflect new and updated OECD test guidelines, as well as reflect on scientific advances in the use of test methods and assessment of the endocrine activity of chemicals. The document is intended to provide guidance for evaluating chemical using standardised test guidelines. Specific objectives include providing a description of the OECD conceptual framework for evaluating chemicals for endocrine disruption, background on the standardised test methods used, and guidance for interpreting the outcome of individual tests. The general approach taken by the document is primarily to provide guidance on how test results might be interpreted based on the outcome of standardised assays. Key questions addressed in the document concern likely mechanisms of endocrine action and any resulting apical effects that can be attributed to such action. The document is not proscriptive but provides suggestions for possible next steps in testing (if any) which might be appropriate for a regulatory authority to take, given the various data scenarios. The guidance document is focused primarily on endocrine modalities included in the conceptual framework; estrogen, androgen, and thyroid mediated endocrine disruption and chemicals that interfer with steroidogenesis.
Introduction to Endocrine disrupters
What is an Endocrine Disrupter ?
Endocrine disrupting chemicals (EDSs) are generally defined as substances in our environment, food and consumer products that can disrupt hormonal balance in humans and wildlife and result in adverse health effects.
How work is carried out ?
The work on endocrine disrupters testing and assessment is overseen by the Working Group of National Coordinators of the Test Guidelines Programme (WNT) and managed by four main expert or advisory groups:
- An advisory group on endocrine disrupters testing and assessment (EDTA AG);
- A validation management group on ecotoxicity testing;
- A validation management group on non-animal testing:
- A validation management group for mammalian testing.
The EDTA AG is an advisory group to the WNT and to the VMGs. National experts nominated by the National coordinators and the European Commission, and representatives from the Business and Industry Advisory Committee, Environmental NGOs, and International Council on Animal Protection in OECD Programmes participate in the work.
Why is OECD working on Endocrine Disrupters ?
In the late 1990s, OECD countries decided to take action to develop tools to identify endocrine disrupting chemicals. Based on scientific works and research efforts, OECD started to investigate test methods that could be standardised and used in chemicals regulations to detect and characterise hazards posed by endocrine disrupting chemicals.
Conceptual framework for testing and assessment of endocrine disrupters
The OECD Conceptual Framework for Testing and Assessment of Endocrine Disrupters (as revised in 2012) lists the OECD Test Guidelines and standardized test methods available, under development or proposed that can be used to evaluate chemicals for endocrine disruption. The Conceptual Framework is intended to provide a guide to the tests available which can provide information for endocrine disrupters’ assessment but is not intended to be a testing strategy. Furthermore, this Conceptual Framework does not include evaluation of exposure; however this should be included when deciding whether further testing is needed. Further information regarding the use and interpretation of these tests is available in Guidance Document No. 150.
Mammalian and Non Mammalian Toxicology
Existing Data and existing or new non-Test Information
- Physical & chemical properties, e.g., MW reactivity, volatility, biodegradability.
- All available (eco)toxicological data from standardized or non-standardized tests.
- Read across, chemical categories, QSARs and other in silico predictions, and ADME model predictions.
In vitro assays providing data about selected endocrine mechanism(s) / pathways(s) (Mammalian and non mammalian methods)
- Estrogen (OECD TG 493) or androgen receptor binding affinity (US EPA TG OPPTS 890.1150)
- Estrogen receptor transactivation (OECD TG 455, ISO 19040-3), yeast estrogen screen (ISO 19040-1 & 2) TG 457).
- Androgen receptor transactivation (OECD TG 458).
- Steroidogenesis in vitro (OECD TG 456).
- Aromatase assay (US EPA TG OPPTS 890.1200)
- Thyroid disruption assays (e.g. thyroperoxidase inhibition, transthyretin binding)
- Retinoid receptor transactivation assays
- Other hormone receptors assays as appropriate
- High-throughput screens
Non Mammalian Toxicology
In vivo assays providing data about selected endocrine mechanism(s) / pathway(s)
- Uterotrophic assay (OECD TG 440).
- Hershberger assay (OECD TG 441).
- Amphibian metamorphosis assay (OECD TG 231).
- Fish short-term reproduction assay (FSTRA) (OECD TG 229).
- 21-day fish assay (OECD TG 230).
- Androgenized female stickleback screen (AFSS) (OECD GD 148).
- EASZY Assay. Detection of Substances Acting through Estrogen Receptors using Transgenic cyp19a1b GFP Zebrafish Embryos (draft OECD TG).
- Xenopus embryonic thyroid signalling assay (XETA) (draft OECD TG).
- Juvenile medaka anti-androgen screening assay (JMASA) (draft OECD GD).
- Short-term juvenile hormone activity screening assay using Daphnia magna (draft OECD TG).
- Rapid androgen disruption adverse outcome reporter (RADAR) assay (draft OECD TG).
In vivo assays providing data on adverse effects on endocrine relevant endpoints
- Repeated dose 28-day study (OECD TG 407).
- Repeated dose 90-day study (OECD TG 408).
- Pubertal development and thyroid function assay in peripubertal male rats (PP male assay) (US EPA TG OPPTS 890.1500)
- Pubertal development and thyroid function assay in peripubertal female rats (PP female assay) (US EPA TG OPPTS 890.1450)
- Prenatal developmental toxicity study (OECD TG 414).
- Combined Chronic toxicity and carcinogenicity studies (OECD TG 451-3).
- Reproduction/developmental toxicity screening test (OECD TG 421).
- Combined repeated dose toxicity study with the reproduction/developmental toxicity screening test (OECD TG 422).
- Developmental neurotoxicity (OECD TG 426).
- Repeated dose dermal toxicity: 21/28-day study (OECD TG 410).
- Subchronic dermal toxicity: 90-day study (OECD TG 411).
- 28-day (subacute) inhalation toxicity study (OECD TG 412).
- Subchronic inhalation toxicity: 90-day study (OECD TG 413).
- Repeated dose 90-day oral toxicity study in non-rodents (OECD TG 409).
- Fish sexual development test (FSDT) (OECD TG 234).
- Larval Amphibian Growth & Development Assay (LAGDA) (OECD TG 241).
- Avian Reproduction Assay (OECD TG 206).
- Fish early life stage (FELS) toxicity test (OECD TG 210).
- New guidance document on harpacticoid copepod development and reproduction test with Amphiascus (OECD GD 201).
- Potamopyrgus antipodarum reproduction test (OECD TG 242).
- Lymnaea stagnalis reproduction test (OECD TG 243).
- Chironomid Toxicity Test (TG 218 & TG 219).
- Daphnia Magna reproduction test (with male induction) (OECD TG 211).
- Earthworm Reproduction Test (OECD TG 222).
- Enchytraeid Reproduction Test (OECD TG 220).
- Sediment Water Lumbriculus Toxicity Test Using Spiked Sediment (OECD TG 225).
- Predatory mite reproduction test in soil (OECD TG 226).
- Collembolan Reproduction Test in Soil (OECD TG 232).
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.
- Extended one-generation reproductive toxicity study (EOGRTS) (OECD TG 443).
- Two-generation reproduction toxicity study (OECD TG 416, most recent update).
- Fish Life Cycle Toxicity Test (FLCTT) (US EPA TG OPPTS 850.1500).
- Medaka Extended One-Generation Reproduction Test (MEOGRT) (OECD TG 240).
- Avian two-generation toxicity test in the Japanese quail (ATGT) (US EPA TG OCSPP 890.2100/740-C-15-003).
- Sediment Water Chironomid Life Cycle Toxicity Test (OECD TG 233).
- Daphnia Multigeneration test for assessment of EDCs (draft OECD TG).
- Zebrafish extended one-generation reproduction test (ZEOGRT) (draft OECD TG).
Other Relevant Publications
Workshop Report No. 118
The Workshop on OECD Countries Activities Regarding Testing, Assessment and Management of Endocrine Disrupters held in September 2009 in Copenhagen, recommended the above documents in parallel with the continuous development of Test Guidelines for the screening and testing of endocrine disrupters.
Guidance Document No. 150
This Guidance Document in the OECD Series on Testing and Assessment was developed in 2012 to support regulatory authorities’ decisions related to the hazard of specific chemicals and toxicologically-relevant metabolites when they receive test results from a Test Guideline or draft Test Guideline for the screening/testing of chemicals for endocrine disruption. The guidance is worded to permit flexible interpretation in the context of different domestic legislation, policies and practice.
It also provides guidance on how to interpret the outcome of individual tests, taking into account existing information, and how to increase evidence on whether or not a substance may be an endocrine disrupter. It recommends test methods that may be performed if regulatory authorities need more evidence. The test methods are defined precisely so that countries’ possible testing requirements can be harmonised and hence ensure the Mutual Acceptance of Data. As for 2017, the Guidance Document 150 is being updated. A new edition should be released in 2018.
Review Paper No. 178
The detailed Review Paper No. 178 on the state of science on novel in vitro and in vivo screening and testing methods and endpoints for evaluating endocrine disrupters was developed by the United States, in cooperation with the European Commission. To date, OECD work related to endocrine disrupters focused on oestrogen/androgen and thyroid pathways. However, other endocrine and neuro-endocrine pathways may also have adverse outcomes, such as symptoms of metabolic syndrome, reproductive dysfunction, altered foetal development.
Brochure: OECD work on Endocrine Disrupting Chemicals
The endocrine disrupting chemicals brochure explains why and how OECD became a key player on the issue of endocrine disrupters testing and assessment over the last two decades.
The brochure provides background on endocrine disrupters and outlines major achievements.
Using the validated methodologies available through OECD, regulatory authorities can use internationally harmonised tools to evaluate chemicals of concern for human health and/or the environment.
With the financial assistance of the European Union
The OECD Endocrine Disrupters project has been produced with the financial assistance of the European Union. The views expressed herein can in no way be taken to reflect the official opinion of the European Union.
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