Essais des produits chimiques

OECD Work Related to Endocrine Disrupters

 

 

 

Introduction

The protection of human health and the environment from endocrine disrupters is currently a high priority for regulatory authorities in most OECD countries/regions, and it has been proposed by UNEP as a SAICM policy emerging issue. Indeed, the OECD Test Guidelines Programme has spent approximately half of its resources since 1996 to develop Test Guidelines and other tools to support countries’ needs related to testing and assessment of chemicals for endocrine disruption.

 

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 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.

 

Outcome of the OECD work

After more than 10 years working on the validation and development of methods for screening and testing chemicals for endocrine disruption, the Workshop on OECD Countries’ Activities Regarding Testing, Assessment and Management of Endocrine Disrupters, held in September 2009 in Copenhagen, recommended further work for OECD, and in particular
(i) the development of a guidance document for the assessment of endocrine disrupters,
(ii) the revision of the 2002 Conceptual Framework for Testing and Assessment of Endocrine Disrupters, and
(iii) the development of a detailed review paper on endpoints that are not included in existing Test Guidelines.
   


In parallel with the continuous development of Test Guidelines for the screening and testing of endocrine disrupters, other documents recommended by the Copenhagen workshop have been developed (see below).

 

Conceptual framework for testing and assessment of endocrine disrupters

A Conceptual Framework (CF) for the Testing and Assessment of Endocrine Disrupters was adopted in 2002. The CF is not a testing strategy; it is not prescriptive and simply reflects the type of information the tests provide at the different levels, such as informing endocrine toxicity outcome pathways, moving from in silico to in vitro and in vivo. It should be noted that information on mechanisms/pathways is particularly important for assessing chemicals for endocrine disruption.

An updated CF was approved by the WNT in April 2012. It includes all published Test Guidelines listed in (Table 1) of this document; test methods for which inclusion in the Test Guidelines work plan has been approved by the WNT  (Table 2); some existing Test Guidelines not specifically developed for screening/testing of chemicals for endocrine disruption (Table 3), and a few non OECD test methods. The updated CF is attached as an annex to the Guidance Document on Standardized Test Guidelines for Evaluating Chemicals for Endocrine Disrupters.

The revised description of the five levels of the draft CF is as follows:

         Level 1.        Existing data and non test information

         Level 2.        In vitro assays providing data about selected endocrine mechanism(s)/pathway(s)

         Level 3.        In vivo assays providing data about selected endocrine  mechanism(s)/pathway(s)

         Level 4.        In vivo assays providing data on adverse effects on endocrine relevant endpoints

         Level 5.        In vivo assays providing more comprehensive data on adverse effects on endocrine
                               relevant endpoints over extensive parts of the life cycle of the organisms.

Information/tools from lower levels can be used to determine what specific higher level tests are needed for a specific chemical to increase evidence that it is/it is not an endocrine disrupter. This approach is illustrated in the Guidance Document on Standardized Test Guidelines for Evaluating Chemicals for Endocrine Disruption (see below).

OECD EDTA Conceptual Framework

 

Guidance document on standardized test guidelines for evaluating chemicals for endocrine disruption

This Guidance Document No. 150 in the OECD Series on Testing and Assessment was developed by two consultants in close cooperation with the EDTA AG.

This document was developed 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.

More information

 

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

The project to develop this document was led 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.

The document was developed by consultants, in close consultation with the EDTA AG. It has been published as Detailed Review Paper No. 178 in the OECD Series on Testing and Assessment.

 

Test guidelines specifically developed or updated for the screening or testing of chemicals for endocrine disruption

A number of test Guidelines have been published in 2007-2012 and are available free of charge from the ilibrary.

 
Table 1: Published Test Guidelines specifically developed or updated for the screening or testing of chemicals for endocrine disruption

TG

Title

Adoption year

440

Uterotrophic Bioassay in rodents: A short-term Screening Assay for Oestrogenic Properties

2007

407

(updated)

Repeated Dose 28-day Oral Toxicity Study in Rodents

2008

211

(updated)

Daphnia Magna Reproduction Test

2011

441

Hershberger Bioassay in rats: A Short-Term Screening Assay for (Anti)Androgenic Properties

2009

229

Fish Short Term Reproduction Assay

2009

230

21-Day Fish Assay: A Short-Term Screening for Oestrogenic and Androgenic Activity, and Aromatase Inhibition

2009

231

Amphibian Metamorphosis Assay

2009

455

Stably Transfected Human Oestrogen Receptor-α Transcriptional Activation Assay for the Detection of Oestrogenic Agonist Activity of Chemicals

2009

233

Sediment-Water Chironomid Life-Cycle Toxicity Test Using Spiked Water or Spiked Sediment

2010

234

Fish Sexual Development Test

2011

456

H295R Steroidogenesis Assay

2011

457

BG1Luc Estrogen Receptor Transactivation in vitro Assay to Detect Estrogen Receptor Agonists and Antagonists

2012

 

Projects currently on the workplan in relation to endocrine disrupters testing and assessment

 

The work plan of the Test Guideline Programme includes projects for other Test Guidelines for screening/testing chemicals for endocrine disruption.

 

Table 2: Projects for the screening or testing of chemicals for endocrine disruption, currently on the work plan

Project

Lead Country
Fish Life-Cycle Test/Medaka Multi-Generation Test USA/JPN/DEU
Fish Reproduction/Partial Lifecycle Test  USA
Larval Amphibian Growth and Development Assay  USA/JPN
Xenopus Embryonnic Thyroid Assay  FRA
 Zebrafisg Embryo Assay for the detection of endocrine active substances acting through the estrogen receptor  FRA
Mysid Life Cycle Toxicity Test  USA
Copepod Reproduction and Development Test  SWE
Mollusc Reproductive Toxicity Tests – Development and Validation of Test Guidelines  DEU/GBR/FRA/DNK
Avian 2-Generation Reproductive Toxicity Assay  USA
Human Recombinant Oestrogen Receptor Alpha Binding Assay  USA/EC/DEU/JPN
STTA Assay for the Detection of Androgenic and Anti-Androgenic Activity  JPN
STTA Assay for the detection of Anti-Oestrogenic activity of chemicals  JPN
Performance-Based Test Guideline for the Androgen Receptor Transactivation Assay  EC
Transcriptional Assay for the Detection of Estrogenic and Anti-Estrogenic Compounds using MELN Cells  EC
Thyroid Scoping Document  OECD Secr.
Update of TG 421 and TG 422 with ED-relevant endpoints  DK

 

Other useful information


A number of existing Test Guidelines may also provide useful information for the assessment of endocrine disrupters. They are available free of charge from the ilibrary.

 

Table 3: Adopted Test Guidelines that may provide useful information, although not specifically developed for screening/testing chemicals for endocrine disruption

Name TG Number Year of Adoption
One-Generation Reproduction Toxicity Study TG 415 1983
Two-Generation Reproduction Toxicity TG 416 2001
 Reproduction/Developmental Toxicity Screening Test TG 421 1995
 Combined Repeated Dose Toxicity Study with the Reproduction/Developmental Toxicity Screening Test TG 422 1996
 Carcinogenicity and Reproductive Toxicity Studies TG 451-453 2009
 Prenatal Development Toxicity Study TG 414  2001
 Repeated Dose 90-Day Oral Toxicity Study in Rodents TG 408 1998
 Development Neurotoxicity Study TG 426 2007
 Avian Reproduction TG 206 1984
 Chironomid Toxicity Test TG 218-219 2004
 Extended One –Generation Reproductive Toxicity Study  TG 443  2011

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

See also in the Series on Testing and Assessment: publications related to endocrine disrupters

 

 

 

 

 

 

 

 

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