Main issues addressed in the 2014–2015 revisions to the OECD Genetic Toxicology Test Guidelines

Abstract

The Organization for Economic Cooperation and Development (OECD) recently revised the test guidelines (TGs) for genetic toxicology. This article describes the main issues addressed during the revision process, and the new and consistent recommendations made in the revised TGs for: (1) demonstration of laboratory proficiency; (2) generation and use of robust historical control data; (3) improvement of the statistical power of the tests; (4) selection of top concentration for in vitro assays; (5) consistent data interpretation and determination of whether the result is clearly positive, clearly negative or needs closer consideration; and, (6) consideration of 3R's for in vivo assay design. The revision process resulted in improved consistency among OECD TGs (including the newly developed ones) and more comprehensive recommendations for the conduct and the interpretation of the assays. Altogether, the recommendations made during the revision process should improve the efficiency, by which the data are generated, and the quality and reliability of test results. Environ. Mol. Mutagen. 58:284-295, 2017. © 2017 Wiley Periodicals, Inc.

Critical review of styrene genotoxicity focused on the mutagenicity/clastogenicity literature and using current organization of economic cooperation and development guidance

“…The available literature evaluating the potential mutagenicity/clastogenicity of styrene and SO exposure includes most, but not all, of the standard in vitro mammalian cell and rodent in vivo tests for which there are OECD TGs. We note that in the recent OECD revision process, all the genetic toxicology TGs were considered for revision or deletion (OECD, ; Thybaud et al, ). The TGs for several assays were archived/deleted.…”

“…The recently revised OECD TGs for the standard genetic toxicology assays provide improved guidance concerning assay conduct, acceptance criteria for individual test results, and an overall strategy for interpreting test data (positive/negative). A publication by Thybaud et al () and an OECD document entitled “Overview of the set of OECD Genetic Toxicology Guidelines and updates performed in 2014–2015” (OECD, ) provide details concerning the deliberations upon which the revisions were based and an overview of the most significant changes from previous versions of the TGs. TG471 for the Ames test was not revised and therefore there are no new considerations for the interpretation of data from this assay.…”

“…After these reviews were published, the Organization of Economic Cooperation and Development (OECD) made substantial revisions to the genotoxicity test guidelines (TGs), and these revisions affect the conduct of assays and the interpretation of test results (OECD, ; Thybaud et al, ). In addition, there have been a few recent publications addressing the potential genotoxicity of styrene/SO.…”

Applied genetic toxicology: From principles to practice

“…Dr. Galloway provides a historical frame of reference for the ICH guidelines, given the concurrent efforts to update the Organization for Economic Cooperation and Development (OECD) guidelines and the first meetings of the International Workshops on Genotoxicity Testing (IWGT). Recent updates to the OECD testing guidelines for genetic toxicology are summarized in this issue by contributors to the OECD updates, who focus on the main issues resolved during the recent revision process [Thybaud et al, ]. In addition, Robert Przygoda reviews the development and applicability of the recently revised ISO 10993–3 international standard for evaluating the genotoxicity, carcinogenicity, and reproductive toxicity potential of medical devices [Przygoda, ].…”

“…Similarly, the recent efforts to update the OECD testing guidelines for genetic toxicology, reviewed here by Thybaud and colleagues, have strengthened elements of the individual test guidelines to improve the efficiency, quality, and reliability of test results, including new requirements for establishing laboratory proficiency, improving historical control data and statistical power, and recommendations for ensuring consistent data interpretation [Thybaud et al, ]. Such improvements directly benefit the processes of regulatory safety assessment and human health risk assessment, where there are ongoing efforts to improve the consistency and transparency of evidence integration when evaluating the toxicity of chemicals.…”