Testing of chemicals

OECD Work Related to Endocrine Disrupters

 

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.

What's new

 ‌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 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

Level 1

Existing Data and 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.

Level 2

In vitro assays providing data about selected endocrine mechanism(s) / pathways(s) (Mammalian and non mammalian methods)

  • Estrogen or androgen receptor binding affinity (OECD TG 493).
  • Estrogen receptor transactivation (OECD TG 455 & TG 457).
  • Androgen transactivation assay (OECD TG 458).
  • Steroidogenesis in vitro (OECD TG 456).
  • MCF-7 cell proliferation assays (ER ant/agonist).
  • Other assays as appropriate.
 

Mammalian and Non Mammalian Toxicology

Mammalian and Non Mammalian Toxicology

Level 3

In vivo assays providing data about selected endocrine mechanism(s) / pathway(s)

  • Uterotrophic assay (OECD TG 440).
  • Hershberger assay (OECD TG 441).
  • Xenopus embryo thyroid signalling assay (When/if TG is available).
  • Amphibian metamorphosis assay (OECD TG 231).
  • Fish Reproductive Screening Assay (OECD TG 229).
  • Fish Screening Assay (OECD TG 230).
  • Androgenized female stickleback screen (OECD ).

Level 4

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).
  • 1-generation reproduction toxicity study (OECD TG 415).
  • Male pubertal assay (see GD 150, Chapter C4.3).
  • Female pubertal assay (see GD 150, Chapter C4.4).
  • Intact adult male endocrine screening assay (see GD 150, Chapter Annex 2.5).
  • Prenatal developmental toxicity study (OECD TG 414).
  • Chronic toxicity and carcinogenicity studies (OECD TG 451-3).
  • Reproductive screening test (OECD TG 421).
  • Combined 28-day/reproductive screening assay (OECD TG 422).
  • Developmental neurotoxicity (OECD TG 426).
  • Fish sexual development test (OECD TG 234).
  • Fish Reproduction Partial Lifecycle Test (when/If TG is Available).
  • Larval Amphibian Growth & Development Assay (OECD TG 241).
  • Avian Reproduction Assay (OECD TG 206).
  • Mollusc Partial Lifecycle Assays (OECD TG 242 & TG 243).
  • Chironomid Toxicity Test (TG 218 & TG 219).
  • Daphnia 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.

  • Extended one-generation reproductive toxicity study (OECD TG 443).
  • 2-Generation reproduction toxicity study (OECD TG 416).
  • FLCTT (Fish LifeCycle Toxicity Test) (when TG is available).
  • Medaka Extended One Generation Reproduction Toxicity Study Test (OECD TG 240).
  • Avian 2 generation reproductive toxicity assay (when TG is available).
  • Mysid Life Cycle Toxicity Test (when TG is available).
  • Copepod Reproduction and Development Test (when TG is available).
  • Sediment Water Chironomid Life Cycle Toxicity Test (OECD TG 233);
  • Mollusc Full Lifecycle Assays (when TG is available).
  • Daphnia Multigeneration Assay (if TG is available).

 

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.

 

 

Related Documents