A host of new and revised OECD test guidelines feature in vitro methods

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A host of new and revised OECD test guidelines feature in vitro methods

by Marilyn Matevia, Humane Society of the United States
The Organisation for Economic Co-operation and Development (OECD) establishes guidance for commerce and trade between its 34 member countries, which include countries in Europe, the United States, Canada, Mexico, Australia, New Zealand, Japan, and South Korea, with Brazil, India, Indonesia, the People’s Republic of China and South Africa participating as Key Partners. Guidance for assessing the safety of chemicals in commerce is developed as part of the OECD’s Test Guidelines Programme, which consults “the most relevant internationally agreed testing methods used by governments, industry and independent laboratories…” The aim of the Test Guideline Programme is to harmonize safety testing methods and standards across member countries, so that all members can “fully benefit from the OECD agreement on Mutual Acceptance of Data and avoid duplicative testing.” Under this agreement, safety test results obtained according to OECD test guidelines in one member country will be accepted in others, eliminating the need to repeat safety tests for each new market. Test Guidelines (TGs) are regularly reviewed and updated to incorporate advances in science, changes in regulatory needs, and considerations of animal welfare.

This spring, the OECD’s Working Group of the National Coordinators for the Test Guidelines Programme approved a number of new and updated Test Guidelines that will expand options for the use of in vitro methods in the areas of skin and eye irritation, estrogen activity, and mutagenicity. Additionally, two TGs describing new approaches for assessing skin irritation potential were adopted by the OECD in Feburary 2015. Following is a list of these guidelines, with brief descriptions of the applicability of the new methods and changes introduced to the updated TGs.

New Test Guidelines

TG 491: Reconstructed Human Cornea-like Epithelium (RHCE) Test Method for Identifying Chemicals not Requiring Classification and Labelling for Eye Irritation or Serious Eye Damage. This is the first TG for ocular testing to use reconstructed human tissue rather than ex vivo animal tissue. It is based on the EpiOcular™ Eye Irritation Test (EIT) to assess chemicals that do not require classification according to the UN Globally Harmonized System of Classification and Labelling of Chemicals (GHS). The test is to be used in combination with other recommended alternatives, in order to replace the Draize rabbit eye test.

TG 492: Test Guideline on the In Vitro Mammalian Cell Gene Mutation Tests Using the Thymidine Kinase Gene. This is one of a series of guidelines on genetic toxicology. The purpose of this TG is to distinguish between tests using the Thymidine Kinase gene from test using the Hprt and xprt genes, previously in the same TG, and to incorporate harmonized recommendations for assay acceptance criteria and data interpretation.

TG 493: Performance-Based Test Guideline for Human Recombinant Estrogen Receptor (hrER) In Vitro Assays to Detect Chemicals with ER Binding Affinity and Performance Standards. Performance-based test guidelines (PBTG) are designed to allow use of different methods that address the same biological process, with the new method to be validated by comparison to Performance Standards. TG 493 is based on two fully validated methods for hrER binding.

PBTG 455: Performance Based Test Guideline for Stably Transfected Transactivation In Vitro Assays to Detect Estrogen Receptor Agonists and Antagonists. This PBTG describes several methods to detect ER antagonists.

New Guidelines published in February 2015

TG 442C: In Chemico Skin Sensitisation: Direct Peptide Reactivity Assay (DPRA). This guideline describes an in chemico procedure that addresses the molecular initiating event in the skin sensitization AOP, protein reactivity.

TG 442D: In Vitro Skin Sensitisation: ARE-Nrf2 Luciferase Test Method. This guideline describes an in vitro method for measuring gene expression in ARE-dependent pathways, one of the indicators of the second key event in the skin sensitization AOP.

Updated Test Guidelines

Test guidelines for skin corrosion and irritation have been updated to include references to the New Guidance Document on an Integrated Approach on Testing and Assessment (IATA) for Skin Corrosion and Irritation (Series on Testing and Assessment, No. 203). Additional revisions are described below.

  • TG 404: Acute Dermal Irritation/Corrosion. This animal test method has been revised to emphasize steps to avoid unnecessary animal testing, and refines an in vivo test patch procedure to address animal welfare concerns.
  • TG 430: In Vitro Skin Corrosion: Transcutaneous Electrical Resistance Test Method (TER).
  • TG 431: In Vitro Skin Corrosion: Reconstructed Human Epidermis (RHE) Test Method. This method is revised to include an alternative method to measure viability, the HPLC/UPLC-spectrophotometry procedure.
  • TG 435: In Vitro Membrane Barrier Test Method for Skin Corrosion. The list of proficiency substances on which laboratories must demonstrate technical proficiency (in using this in vitro method) is updated.
  • TG 439: In Vitro Skin Irritation – Reconstructed Human Epidermis Test Method. This TG also introduces the HPLC/UPLC-spectrophotometry procedure as an alternative to measure viability.
  • TG 476: In Vitro Mammalian Cell Gene Mutation Tests. Methods using the Hprt and Xprt genes have been updated to remove the method detecting the thymidine kinase gene (now described in TG 492).

These and other OECD guidelines are (or will soon be) available here.

Readers should also be aware of the OECD’s Guidance Document for Describing Non-Guideline In Vitro Test Methods, published in December 2014. Recognizing that information from non-guideline studies “can be useful at several levels in the safety assessment process,” this document provides a template for presenting that information to facilitate its evaluation by regulators.

*Note: the long-awaited Test Guideline for in vitro skin sensitization using the h-CLAT method is undergoing minor revisions and is expected to be approved by written procedure during the next year.

Posted: July 22, 2015

Showing 2 comments
  • Prof S V S Rana

    Please focus on the development of toxicology in developing countries.

    • AltTox

      Thanks for the feedback. Watch for new additions to our Programs & Policy pages in the coming months.