Are all bacterial strains required by OECD mutagenicity test guideline TG471 needed?

Autor: Williams RV; Lhasa Limited, 2 Canal Wharf, Leeds, LS11 5PS, United Kingdom. Electronic address: richard.williams@lhasalimited.org., DeMarini DM; U.S. Environmental Protection Agency, Research Triangle Park, NC, 27511, United States., Stankowski LF Jr; Charles River Laboratories - Skokie, LLC, 8025 Lamon Ave., Skokie, IL, 60077, United States., Escobar PA; Merck & Co., West Point, PA, 19486, United States., Zeiger E; Errol Zeiger Consulting, 800 Indian Springs Road, Chapel Hill, NC, 27514, United States., Howe J; Glaxo Smith Kline R&D, Park Road, Ware, Hertfordshire, SG12 0DP, United Kingdom., Elespuru R; U.S. Food and Drug Administration, 10903 New Hampshire Avenue, Silver Spring, MD, 20993, United States., Cross KP; Leadscope, Inc., 1393 Dublin Rd, Columbus, OH, 43215, United States.
Jazyk: angličtina
Zdroj: Mutation research. Genetic toxicology and environmental mutagenesis [Mutat Res Genet Toxicol Environ Mutagen] 2019 Dec; Vol. 848, pp. 503081. Date of Electronic Publication: 2019 Aug 09.
DOI: 10.1016/j.mrgentox.2019.503081
Abstrakt: The International Workshop on Genotoxicity Testing (IWGT) meets every four years to seek consensus on difficult or conflicting approaches to genotoxicity testing based upon experience, available data, and analysis techniques. At the 2017 IWGT meeting in Tokyo, one working group addressed the sensitivity and selectivity of the bacterial strains specified in the Organization for Economic Cooperation and Development (OECD) Test Guideline TG471 to recommend possible modification of the test guideline. Three questions were posed: (1) Although TA100 is derived from TA1535, does TA1535 detect any mutagens that are not detected by TA100? (2) Among the options of Salmonella TA1537, TA97 or TA97a, are these strains truly equivalent? (3) Because there is a choice to use one of either E. coli WP2 uvrA, E. coli WP2 uvrA pKM101, or Salmonella TA102, are these strains truly equivalent? To answer these questions, we analyzed published bacterial mutation data in multiple strains from large (>10,000 compound) databases from Leadscope and Lhasa Limited and anonymized data for 53 compounds tested in TA1535 and TA100 provided by a pharmaceutical company. Our analysis involved (1) defining criteria for determining selective responses when using different strains; (2) identifying compounds producing selective responses based upon author calls; (3) confirming selective responses by visually examining dose-response data and considering experimental conditions; (4) using statistical methods to quantify the responses; (5) performing limited additional direct-comparison testing; and (6) determining the chemical classes producing selective responses. We found that few mutagens would fail to be detected if the test battery did not include Salmonella strains TA1535 (8/1167), TA1537 (2/247), TA102 (4/46), and E. coli WP2 uvrA (2/21). Of the mutagens detected by the full TG471 strain battery, 93% were detected using only strains TA98 and TA100; consideration of results from in vitro genotoxicity assays that detect clastogenicity increased this to 99%.
(Copyright © 2019 The Authors. Published by Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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