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.
Endocrine disrupters
The OECD develops test guidelines and other tools to support countries’ needs related to testing and assessment of chemicals for endocrine disrupters.
What is an endocrine disruptor?
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.
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.
Conceptual framework for testing and assessment of endocrine disrupters
The OECD Conceptual Framework for Testing and Assessment of Endocrine Disrupters described on this page is up to date (October 2024) and lists the OECD Test Guidelines and standardized test methods available 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 an evaluation of exposure. This should be included when deciding whether further testing is needed.
Level 1
Existing Data and existing or new non-test Information
Mammalian and Non Mammalian Toxicology
- Physical & chemical properties, e.g., MW reactivity, volatility, biodegradability.
- All available (eco)toxicological data from standardised or non-standardised tests.
- Read across, chemical categories, QSARs and other in silico predictions, and ADME model predictions.
Level 2
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
Level 3
In vivo assays providing data about selected endocrine mechanism(s) / pathway(s)
Non Mammalian Toxicology
- Fish short-term reproduction assay (FSTRA) (OECD TG 229).
- 21-day fish assay (OECD TG 230).
- Amphibian metamorphosis assay (OECD TG 231).
- Xenopus embryonic thyroid signalling assay (XETA) (OECD TG 248).
- EASZY Assay. Detection of Substances Acting through Estrogen Receptors using Transgenic cyp19a1b GFP Zebrafish Embryos (OECD TG 250).
- Rapid androgen disruption activity reporter (RADAR) assay (OECD TG 251).
- Rapid Estrogen Activity In Vivo (REACTIV) assay (OECD TG 252).
- Short-term juvenile hormone activity screening assay using Daphnia magna (JHASA) (OECD TG 253).
- Androgenized female stickleback screen (AFSS) (OECD GD 148).
- Juvenile medaka anti-androgen screening assay (JMASA) (OECD GD 379).
Level 4
In vivo assays providing data on adverse effects on endocrine relevant endpoints
Mammalian Toxicology
- 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).
Non Mammalian Toxicology
- 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).
Level 5
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.
Non Mammalian Toxicology
- 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).
Interpreting the results from Test Guidelines
Guidance Document No. 150, Second edition
This Guidance Document supports 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.
This guidance document was 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 requires a new update to take into account recently adopted Test Guidelines and other standardised methods, as well as revisit guidance on evaluation of data on the basis of experince gained and lessons learnt in countries that have relevant regulatory programmes. Resources permitting, the OECD will re-open the Guidance Document 150.
Other relevant publications
- Workshop report on OECD countries activities regarding testing, assessment and management of endocrine disrupters
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.
- 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
The detailed Review Paper 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.
- Thyroid in vitro methods: assessment reports by the thyroid disruption methods expert group - Reports assessing the validation status of assays from the EU-NETVAL activities
The OECD Test Guidelines Programme established in 2022 a group of experts on methodologies to test and evaluate chemicals for their thyroid disruption properties. Thyroid function is a complex process where multiple biological mechanisms are at stake and represent as many targets of chemical perturbation. Between 2014 and 2024, member countries and dedicated research centres have devoted resources to developing and standardising in vitro assays for thyroid disruption. This document includes consensus reports from OECD on the assessment of the validation status of individual thyroid in vitro assays from the EU-NETVAL activity in the period 2017-2022; assays are listed in chronological order of their progression in the assessment process.
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.
