Bacterial mutagenicity test data: collection by the task force of the Japan pharmaceutical manufacturers association
Tóm tắt
Ames test is used worldwide for detecting the bacterial mutagenicity of chemicals. In silico analyses of bacterial mutagenicity have recently gained acceptance by regulatory agencies; however, current in silico models for prediction remain to be improved. The Japan Pharmaceutical Manufacturers Association (JPMA) organized a task force in 2017 in which eight Japanese pharmaceutical companies had participated. The purpose of this task force was to disclose a piece of pharmaceutical companies’ proprietary Ames test data. Ames test data for 99 chemicals of various chemical classes were collected for disclosure in this study. These chemicals are related to the manufacturing process of pharmaceutical drugs, including reagents, synthetic intermediates, and drug substances. The structure-activity (mutagenicity) relationships are discussed in relation to structural alerts for each chemical class. In addition, in silico analyses of these chemicals were conducted using a knowledge-based model of Derek Nexus (Derek) and a statistics-based model (GT1_BMUT module) of CASE Ultra. To calculate the effectiveness of these models, 89 chemicals for Derek and 54 chemicals for CASE Ultra were selected; major exclusions were the salt form of four chemicals that were tested both in the salt and free forms for both models, and 35 chemicals called “known” positives or negatives for CASE Ultra. For Derek, the sensitivity, specificity, and accuracy were 65% (15/23), 71% (47/66), and 70% (62/89), respectively. The sensitivity, specificity, and accuracy were 50% (6/12), 60% (25/42), and 57% (31/54) for CASE Ultra, respectively. The ratio of overall disagreement between the CASE Ultra “known” positives/negatives and the actual test results was 11% (4/35). In this study, 19 out of 28 mutagens (68%) were detected with TA100 and/or TA98, and 9 out of 28 mutagens (32%) were detected with either TA1535, TA1537, WP2uvrA, or their combination. The Ames test data presented here will help avoid duplicated Ames testing in some cases, support duplicate testing in other cases, improve in silico models, and enhance our understanding of the mechanisms of mutagenesis.
Tài liệu tham khảo
Maron DM, Ames BN. Revised methods for the Salmonella mutagenicity test. Mutat Res. 1983;113(3-4):173–215. https://doi.org/10.1016/0165-1161(83)90010-9.
Mortelmans K, Zeiger E. The Ames Salmonella/microsome mutagenicity assay. Mutat Res. 2000;455(1-2):29–60. https://doi.org/10.1016/s0027-5107(00)00064-6.
OECD. Guideline for the Testing of Chemicals: Bacterial Reverse Mutation Test No. 471 OECD Environment, Health and Safety Publications Series on Testing and Assessment Organization for Economic Cooperation and Development, Paris; 2020. https://doi.org/10.1787/9789264071247-en.
ICH Harmonized Tripartite Guideline, “Guidance on Genotoxicity testing and data interpretation for pharmaceuticals intended for human use”, S2 (R1), current step 4 version, 2011. https://database.ich.org/sites/default/files/S2_R1_Guideline.pdf.
ICH Harmonized Tripartite Guideline, “Assessment and control of DNA reactive (mutagenic) impurities in pharmaceuticals to limit potential carcinogenic risk”, M7 (R1), current step 4 version, 2017. https://database.ich.org/sites/default/files/M7_R1_Guideline.pdf
Landry C, Kim MT, Kruhlak NL, Cross KP, Saiakhov R, Chakravarti S, et al. Transitioning to composite bacterial mutagenicity models in ICH M7 (Q) SAR analyses. Regul Toxicol Pharmacol. 2019;109:104488. https://doi.org/10.1016/j.yrtph.2019.104488.
Benigni R, Bossa C. Data-based review of QSARs for predicting genotoxicity: the state of the art. Mutagenesis. 2019;34(1):17–23. https://doi.org/10.1093/mutage/gey028.
Honma M. An assessment of mutagenicity of chemical substances by (quantitative) structure-activity relationship. Genes Environ. 2020;42(1):23. https://doi.org/10.1186/s41021-020-00163-1.
Kato M, Sugiyama K, Fukushima T, Miura Y, Awogi T, Hikosaka S, et al. Negative and positive control ranges in the bacterial reverse mutation test: JEMS/BMS collaborative study. Genes Environ. 2018;40(1):7. https://doi.org/10.1186/s41021-018-0096-1.
Levy DD, Hakura A, Elespuru RK, Escobar PA, Kato M, Lott J, et al. Demonstrating laboratory proficiency in bacterial mutagenicity assays for regulatory submission. Mutat Res. 2019;848:403075. https://doi.org/10.1016/j.mrgentox.2019.07.005.
Levy DD, Zeiger E, Escobar PA, Hakura A, van der Leede BM, Kato M, et al. Recommended criteria for the evaluation of bacterial mutagenicity data (Ames test). Mutat Res. 2019;848:403074. https://doi.org/10.1016/j.mrgentox.2019.07.004.
Kazius J, McGuire R, Bursi R. Derivation and validation of toxicophores for mutagenicity prediction. J Med Chem. 2005;48(1):312–20. https://doi.org/10.1021/jm040835a.
Benigni R. Structure-activity relationship studies of chemical mutagens and carcinogens: mechanistic investigations and prediction approaches. Chem Rev. 2005;105(5):1767–800. https://doi.org/10.1021/cr030049y.
Benigni R, Bossa C. Mechanisms of chemical carcinogenicity and mutagenicity: a review with implications for predictive toxicology. Chem Rev. 2011;111(4):2507–36. https://doi.org/10.1021/cr100222q.
Shimizu M, Yano E. Mutagenicity of mono-nitrobenzene derivatives in the Ames test and rec assay. Mutat Res. 1986;170(1-2):11–22. https://doi.org/10.1016/0165-1218(86)90077-7.
Suzuki J, Takahashi N, Kobayashi Y, Miyamae R, Ohsawa M, Suzuki S. Dependence on Salmonella typhimurium enzymes of mutagenicities of nitrobenzene and its derivatives in the presence of rat-liver S9 and norharman. Mutat Res. 1987;178(2):187–93. https://doi.org/10.1016/0027-5107(87)90268-5.
Kim D, Guengerich FP. Cytochrome P450 activation of arylamines and heterocyclic amines. Annu Rev Pharmacol. 2005;45(1):27–49. https://doi.org/10.1146/annurev.pharmtox.45.120403.100010.
Gadaleta D, Manganelli S, Manganaro A, Porta N, Benfenati E. A knowledge-based expert rule system for predicting mutagenicity (Ames test) of aromatic amines and azo compounds. Toxicology. 2016;370:20–30. https://doi.org/10.1016/j.tox.2016.09.008.
Bentzien J, Hickey ER, Kemper RA, Brewer ML, Jane D, Dyekjær JD, et al. An in silico method for predicting Ames activities of primary aromatic amines by calculating the stabilities of nitrenium ions. J Chem Inf Model. 2010;50(2):274–97. https://doi.org/10.1021/ci900378x.
McCarren P, Bebernitz GR, Gedeck P, Glowienke S, Grondine MS, Kirman LC, et al. Avoidance of the Ames test liability for aryl-amines via computation. Bioorg Med Chem. 2011;19(10):3173–82. https://doi.org/10.1016/j.bmc.2011.03.066.
Seifried HE, Seifried RM, Clarke JJ, Junghans TB, San RHC. A compilation of two decades of mutagenicity test results with the Ames Salmonella typhimurium and L5178Y mouse lymphoma cell mutation assays. Chem Res Toxicol. 2006;19(5):627–44. https://doi.org/10.1021/tx0503552CCC.
Yim G, McClure J, Surette MG, Davies JE. Modulation of Salmonella gene expression by subinhibitory concentrations of quinolones. J Antibiotics. 2011;64(1):73–8. https://doi.org/10.1038/ja.2010.137.
Hayasaki Y, Itoh S, Kato M, Furuhama K. Mutagenesis induced by 12 quinolone antibacterial agents in Escherichia coli WP2uvrA/pKM101. Toxicol in Vitro. 2006;20(3):342–6. https://doi.org/10.1016/j.tiv.2005.08.004.
Hakura A, Mizuno Y, Goto M, Kawazoe Y. Studies on chemical carcinogens and mutagens. XXXV. Standardization of mutagenic capacities of several common alkylating agents based on the concentration-time integrated dose. Chem Pharm Bull. 1986;34(2):775–80. https://doi.org/10.1248/cpb.34.775.
Hakura A, Kawazoe Y. Studies on chemical carcinogens and mutagens. XXXVI. Apparent activation energy for mutagenic modification induced in E. coli by alkylating agents. Estimation from mutation frequency. Chem Pharm Bull. 1986;34(4):1728–34. https://doi.org/10.1248/cpb.34.1728.
Kawazoe Y, Tamura N, Yoshimura T. Studies on chemical carcinogens. XXIII. A simple method for characterization of the alkylating ability of compounds by using 4-(p-nitrobenzyl)pyridine. Chem Pharm Bull. 1982;30(6):2077–86. https://doi.org/10.1248/cpb.30.2077.
Snodin DJ. Residues of genotoxic alkyl mesylates in mesylate salt drug substances: real or imaginary problems? Regul Toxicol Pharmacol. 2006;45(1):79–90. https://doi.org/10.1016/j.yrtph.2006.02.003.
Streitwieser A Jr, Wilkins C, Kiehlmann E. Kinetics and isotope effects in solvolyses of ethyl trifluoromethanesulfonate. J Am Chem Soc. 1968;90(6):1598–601. https://doi.org/10.1021/ja01008a601.
Amberg A, Harvey JS, Czich A, Spirkl H-P, Robinson S, White A, et al. Do carboxylic/sulfonic acid halides really present a mutagenic and carcinogenic risk as impurities in final drug products? Org Process Res Dev. 2015;19(11):1495–506. https://doi.org/10.1021/acs.oprd.5b00106.
Mancuso AJ, Swern D. Activated dimethyl sulfoxide: useful reagents for synthesis. Synthesis. 1981;1981(3):165–85. https://doi.org/10.1055/s-1981-29377.
Zeiger E, Anderson B, Haworth S, Lawlor T, Mortelmans K, Speck W. Salmonella mutagenicity tests: III. Results from the testing of 255 chemicals. Environmental Mutagenesis. 1987;9(supplement 9):1–109. https://doi.org/10.1002/em.2860090602.
Nikolaides N, Schipor I, Ganem B. Conversion of amines to phospho esters: decyl diethyl phosphate. Org Synth. 1995;72:246. https://doi.org/10.15227/orgsyn.072.0246.
Jokelainen K, Siitonen A, Jousimies-Somer H, Nosova T, Heine R, Salaspuro M. In vitro alcohol dehydrogenase-mediated acetaldehyde production by aerobic bacteria representing the normal colonic flora in man. Alcoholism. 1996;20(6):967–72. https://doi.org/10.1111/j.1530-0277.1996.tb01932.
Foster RS, Fowkes A, Cayley A, Thresher A, Werner AD, Barber CG, et al. The importance of expert review to clarify ambiguous situations for (Q) SAR predictions under ICH M7. Genes Environ. 2020;42(1):27. https://doi.org/10.1186/s41021-020-00166-y.
Piegorsch WW, Zeiger E. Measuring intra-assay agreement for the Ames Salmonella assay. In: Hothorn L, editor. Statistical methods in toxicology. Lecture notes in medical informatics, vol. 43. Heidelberg: Springer; 1991. p. 35–41. https://doi.org/10.1007/978-3-642-48736-1_5.
Williams RV, DeMarini DM, Stankowski LF Jr, Escobar PA, Zeiger E, Howe J, et al. Are all bacterial strains required by OECD mutagenicity test guideline TG471 needed? Mutat Res. 2019;848:503081. https://doi.org/10.1016/j.mrgentox.2019.503081.