OECD Expands Applicability of Four In Vitro Tests, Publishes New In Vitro Fish Guideline

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In the Spotlight

OECD Expands Applicability of Four In Vitro Tests, Publishes New In Vitro Fish Guideline

Kristie Sullivan, Physicians Committee for Responsible Medicine

Published: August 15, 2013

Last month, the Organisation for Economic Cooperation and Development (OECD) published nine new test guidelines, used by companies and governments worldwide to assess the potential hazards of chemicals. A majority of these (six) are in vitro test guidelines. The Working Group of the National Coordinators of the Test Guidelines Programme (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

For the first time an in vitro test guideline is available for acute fish toxicity testing, using fish embryos. In the EU, fish are not considered animals until they are at the free-swimming larval stage. Test No. 236: Fish Embryo Acute Toxicity (FET) Test allows the user to calculate an acute LC50 for the zebrafish embryo (Danio rario). Validation data for this test are extensively referenced in the test guideline; the method has been used to determine the potential toxicity to fish by a wide variety of substances.

Another first this year is the ability to label substances as “not classified” for eye irritation using revised Bovine Corneal Opacity and Permeability (BCOP) and Isolated Chicken Eye (ICE) test guidelines under the Globally Harmonized System of Classification and Labeling (GHS), along with several other updates. For further explanation on the expanded applicability domain for BCOP and ICE, see the article “Applicability domain of BCOP and ICE extended to identifying ocular non-irritants.”

Three in vitro skin irritation and corrosion test guidelines were also updated this year: Test No. 431: In Vitro Skin Corrosion: Reconstructed Human Epidermis (RHE) Test Method, Test No. 430: In Vitro Skin Corrosion: Transcutaneous Electrical Resistance Test Method (TER), and Test No. 439: In Vitro Skin Irritation – Reconstructed Human Epidermis Test Method. Performance Standards were added for the TER method. A validation exercise was conducted to determine whether the RHE test methods could sub-categorize corrosive substances into GHS 1A, 1B, and 1C categories; the validation was successful and the test guideline now describes procedures for subcategorization between the most severe category, 1A, and the two less severe, 1B-and-1C. Finally, the RHE method for skin irritation, when published in 2010, included three Validated Reference Methods and Performance Standards. A new RHE method, the LabCyte EPIMODEL 24 SIT, was assessed according to the Performance Standards, and, having met them, added to TG 439. This has provided an opportunity for the WNT to showcase the “Performance Standards” model of approving “me too” methods that assess the same endpoint as an existing endpoint, and is meant to ensure open participation in the test guidelines process, guard against test guidelines becoming obsolete due to unforeseen unavailability of key test method components, and speed the process of accepting new in vitro methods.

Guidance Documents

In the past year, OECD has published 10 new documents in the Series on Testing and Assessment. This series of documents includes guidance documents, validation reports, detailed review papers, and other miscellaneous documents. A relatively new type of document is the Streamlined Summary Document (SSD), which the WNT now requests be submitted together with the validation information for many new test guidelines. The SSD is a short summary of the key information needed to communicate the validation status of the method(s) that make up a particular test guideline, and is intended to help regulators and other readers understand the strengths and limitations of the method(s).

Most of the documents relevant to in vitro methods were written to support the revised skin and eye irritation test guidelines, including: No 190: Summary Document on the Statistical Performance of Methods in OECD Test Guideline 431 for Sub-Categorisation, No 189: Streamlined Summary Document Supporting OECD Guideline 437 on the Bovine Corneal Opacity and Permeability for Eye Irritation/Corrosion, and No 188: Streamlined Summary Document Supporting OECD Test Guideline 438 on the Isolated Chicken Eye for Eye Irritation/Corrosion: Part 1; Part 2.

To provide guidance on the development of Adverse Outcome Pathways (AOPs), the OECD published document No. 184: Guidance Document on Developing And Assessing Adverse Outcome Pathways. This is a living document meant to guide scientists and regulators as they “learn by doing.”

To help address inquiries from member countries and the public about AOPs and OECD activities related to AOPs, the OECD has published a new web site with details about what AOPs are and how they can be used, how interested parties can make a proposal to develop an AOP, and a workplan of ongoing AOP-related projects.

Finally, the Work Plan for the Test Guidelines Programme was also published in June of 2013. New projects that may be of interest include:

  • Project 2.46: New TG for the Detection of Endocrine Active Substances, acting through estrogen receptors using transgenic cyp 19a1b-GFP Zebrafish Embryos (EASZY assay)
  • Project 4.71: Updated TG 421/TG 422 (Reproduction/Developmental Toxicity Screening Test)/(Combined Repeated Dose Toxicity Study with the Reproduction/Developmental Toxicity Screening Test), Enhancement with ED-relevant endpoints
  • Project 4.72: Thyroid Scoping Document
  • Project 4.73: New TG: Performance-Based Test Guideline on Androgen Receptor Transactivation Assays
  • Project 4.75: New TG on human Cell Line Activation Test (h-CLAT): an in vitro method for identifying the skin sensitisation potential of chemicals
  • Project 4.76: Performance-Based Test Guideline for the establishment on human-derived hepatic system to investigate biotransformation and toxicity of compounds by evaluation of CYP450 induction competence.

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.