Update on OECD Activities and Publications

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In the Spotlight

Update on OECD Activities and Publications

Kristie Sullivan, Physicians Committee for Responsible Medicine

Published: November 3, 2012

In the past few months, as happens each fall, the Organsation for Economic Co-operation and Development (OECD) has published its newly-approved test guidelines and guidance documents, as well as a current work plan for the Working Group of the National Coordinators of the Test Guidelines Programme (WNT). The WNT is the group within the OECD that drafts and approves new and revised test guidelines and guidance documents, as well as a portion of other documents in the Series on Testing and Assessment.

Test Guidelines

In 2012 there are several new documents that may be of interest to AltTox readers. In fact, every new test guideline this year was either written or revised in order to advance the “3Rs.” Test Guideline (TG) 405: Acute Eye Irritation/Corrosion is the in vivo guideline, updated to include detailed information on providing analgesics and anesthetics to rabbits who are being used in eye irritation testing, as well as stricter language advising study directors to take any and all measures to avoid using animals in eye irritation tests, and a testing strategy one could follow in order to do so. A new in vitro guideline has been adopted for the same endpoint. TG 460: Fluorescein Leakage Test Method for Identifying Ocular Corrosives and Severe Irritants can be used in a testing strategy to test water soluble substances and mixtures for ocular corrosivity (UN GHS/EU CLP/US EPA Category 1). Because it can detect severe ocular irritants, it can be used in a “Top Down” approach for assessing eye irritation. The test detects disruption of the tight junctions of a confluent monolayer of Madin-Darby Canine Kidney (MDCK) cells by assessing the amount of fluorescein dye to penetrate the layer, and was validated in 2009 by EURL ECVAM.

Two new in vitro guidelines assess the potential for endocrine disruption: TG 455: Performance-Based Test Guideline for Stably Transfected Transactivation In Vitro Assays to Detect Estrogen Receptor Agonists and TG 457: BG1Luc Estrogen Receptor Transactivation Test Method for Identifying Estrogen Receptor Agonists and Antagonists. The BG1Luc ERT assay was validated by ICCVAM just this year. TG 455 represents a relatively new approach for the WNT. A “performance-based test guideline (PBTG)” is one that contains one or more methods that are mechanistically and functionally similar as reference methods, along with the important characteristics and performance criteria that a new method should meet in order to be considered a “me too” method. This type of test guideline is meant to encourage the development and speed the acceptance of in vitro methods as well as address the issues with respect to OECD acceptance of patented technology or methods.  [In principle, OECD is reluctant to adopt test guidelines based on proprietary methods unless there is another similar method available; however, the reality is that most new methods involve some proprietary or patented element and the PBTG approach is an attempt to accommodate the use of these methods.]

Guidance Documents

This year OECD has published 14 new documents in the Series on Testing and Assessment. This series includes guidance documents; expert meeting and consultation, chemical assessment, validation, and peer review reports, and now, Adverse Outcome Pathways. Often documents are linked to the adoption of a new test guideline, such as No. 180: Streamlined Summary Document Related to the Fluorescein Leakage (FL) Test Method for Identification of Ocular Corrosives and Severe Irritants (TG 460). This document presents, in a short summary, the supporting evidence for the validation of the FL test method and is meant to be an easily accessible summary based on the full validation background documents. These streamlined summary documents are now being created for each new in vitro test guideline.

Several new publications relate to endocrine disruptor testing, including:

GD181 is a companion to a document published in 2011: No. 150: Guidance Document on Standardised Test Guidelines for Evaluating Chemicals for Endocrine Disruption. GD150 provides guidance on the strategic investigation of a particular chemical or chemicals given the available evidence and test results already obtained, using the tests currently available in the OECD Conceptual Framework for the Screening and Testing of Endocrine Disrupting Chemicals. Although not considered a “testing strategy,” it is hoped that it will help to guide readers to minimize in vivo testing to the greatest extent possible while accomplishing national regulatory goals for information on the potential for endocrine disruption of a particular chemical. The case studies provided in GD 181 are meant to demonstrate the advice provided in GD 150.

Another important publication is No. 171: Fish Toxicity Testing Framework, which aims to take stock of available test guidelines for fish toxicity, eliminate redundancies, and provide advice on minimizing fish testing to member countries and industry. The document goes into great detail, with a survey of regulatory requirements in OECD member countries, chapters on statistical and test considerations, an extensive treatment of the “3Rs” and alternative approaches, a review of current OECD test guideline and those in preparation, and potential fish testing strategies for various situations. An Annex includes specific recommendations for follow-up initiatives and other suggestions to maximize the impact of the document.

One test mentioned in GD 171 is the Zebrafish Embryo Toxicity Test, often termed the FET (fish embryotoxicity test). Validation for this test is ongoing, and this year No. 179: Validation Report (Phase 2) for the Zebrafish Embryo Toxicity Test and Annexes were published. The aim of this phase was to:

further evaluate the intra- and inter-laboratory reproducibility of the ZFET with an additional thirteen chemicals covering specific areas of use (chemicals, pharmaceuticals,  pesticides, biocides), a wide range of toxicity and various modes of action.

The report provides data supporting the conclusion of a successful Phase 2. Work on the test guideline is ongoing at the OECD.

Adverse Outcome Pathways (AOPs) are a way to organize information along a molecular-event-to-adverse-outcome continuum. They can also provide support for category formation or highlight key query points for existing or new mechanistic assays. The first OECD AOP, published after multiple expert consultations, is No. 168: The Adverse Outcome Pathway for Skin Sensitisation Initiated by Covalent Binding to Proteins: Part 1, Part 2. Several other AOPs are now under development, under the management of the Extended Advisory Group on Molecular Screening and Toxicogenomics.

A final publication of note is No. 176: Report on The Retrospective Analysis of 2-Generation Reprotoxicity Data. This document contains two retrospective analyses and supporting information developed during the drafting of TG 443: Extended One-Generation Reproductive Toxicity Study. The first is a 2010 analysis conducted by the Netherlands of two-generation reproductive toxicity studies, the analysis procedure, and conclusions agreed by an expert meeting following the analysis. The second is a retrospective analysis of 350 multi-generation reproductive toxicity studies on pesticides conducted by the US Environmental Protection Agency in 2009.

WNT Work Plan

Finally, the WNT Work Plan for 2012 has been published.
The Work Plan is updated annually, and contains a list of projects on which the WNT is currently working, including yearly updates on the status of current projects. New human-health-related projects include:

  • Transcriptional Assay for the Detection of Estrogenic and Anti-Estrogenic Compounds using the MELN Cells
  • New TG: KeratinoSens: An in vitro Method for Identifying the Skin Sensitisation Potential of Chemicals
  • New TG: Direct Peptide Reactivity Assay (DPRA): An In Chemico Method for Identifying the Skin Sensitisation Potential of Chemicals
  • Updated TG 431: Referencing of EST1000 Skin Corrosion Test in TG 431
  • Updated TG 431: Referencing of SkinEthic Reconstructed Human Epidermis Skin Corrosion Test in TG 431

More information on the OECD and its programs and activities can be found on its web site. The International Council on Animal Protection in OECD Programmes (ICAPO) is a coalition of NGOs located in OECD member country regions that participates in OECD activities and meetings; find out more at ICAPO.org.