{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,4]],"date-time":"2026-05-04T12:07:27Z","timestamp":1777896447787,"version":"3.51.4"},"reference-count":34,"publisher":"Oxford University Press (OUP)","issue":"1","license":[{"start":{"date-parts":[[2024,12,31]],"date-time":"2024-12-31T00:00:00Z","timestamp":1735603200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2024,12,31]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Sugar substitutes are mostly artificial, man-made industrial products used as additives in food and beverages. Most of these substances flow through the digestive tract and food chains, becoming emerging organic contaminants in various abiotic and biotic environmental media. Here, we predict the mutagenicity and carcinogenicity of commonly used sugar substitutes using in silico based methods. The simplified molecular-input line-entry system (SMILES) of sugar substitutes was obtained from the PubChem database for toxicity predictions. Here, sixteen sugar substitutes tested out of these four compounds Glucin (GLU), and 5-nitro-2-propoxyaniline (P-4000), SCL, Ace were predicted as mutagens by using in silico tools such as LAZAR, pKCSM, and Toxtree. Based on the predicted results GLU and P-4000 were predicted as carcinogenic sugar substitutes. Also the study conducted compound gene interaction network to identify the direct connection between sugar substitutes and its corresponding receptors.<\/jats:p>","DOI":"10.1093\/toxres\/tfaf008","type":"journal-article","created":{"date-parts":[[2025,1,10]],"date-time":"2025-01-10T12:19:30Z","timestamp":1736511570000},"source":"Crossref","is-referenced-by-count":5,"title":["Mutagenicity and carcinogenicity prediction of sugar substitutes: an <i>in silico<\/i> approach with compound-gene interactions network"],"prefix":"10.1093","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0737-9749","authenticated-orcid":false,"given":"Charli Deepak","family":"Arulanandam","sequence":"first","affiliation":[{"name":"Department of Medicinal and Applied Chemistry, College of Life sciences, Kaohsiung Medical University , Kaohsiung-80708 ,","place":["Taiwan"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8888-7950","authenticated-orcid":false,"given":"Venkatadri","family":"Babu","sequence":"additional","affiliation":[{"name":"Department of Life Sciences, Ben-Gurion University of the Negev , Beer Sheva-84105 ,","place":["Israel"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yugendhar","family":"Soorni","sequence":"additional","affiliation":[{"name":"School of Chemistry, University of KwaZulu-Natal , Durban ,","place":["South Africa"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4747-1374","authenticated-orcid":false,"given":"Ragothaman","family":"Prathiviraj","sequence":"additional","affiliation":[{"name":"Department of Bioinformatics, Bharathidasan University , Tiruchirappalli, Tamil Nadu 620024 ,","place":["India"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2025,1,17]]},"reference":[{"key":"2025011710152611500_ref1","doi-asserted-by":"publisher","first-page":"640","DOI":"10.3945\/ajcn.112.034751","article-title":"Low-calorie sweetener consumption is increasing in the United States","volume":"96","author":"Sylvetsky","year":"2012","journal-title":"Am J Clin Nutr"},{"key":"2025011710152611500_ref2","doi-asserted-by":"publisher","first-page":"673","DOI":"10.1007\/s40273-014-0243-x","article-title":"The epidemiology of obesity: a big picture","volume":"33","author":"Hruby","year":"2015","journal-title":"PharmacoEconomics"},{"key":"2025011710152611500_ref3","doi-asserted-by":"publisher","first-page":"35","DOI":"10.1016\/j.reprotox.2017.12.006","article-title":"Effects of daily exposure to saccharin sodium and rebaudioside a on the ovarian cycle and steroidogenesis in rats","volume":"76","author":"Jiang","year":"2018","journal-title":"Reprod Toxicol"},{"key":"2025011710152611500_ref4","volume-title":"Non-nutritive sweeteners: consumption trends, consumers perceptions, and metabolic effects","author":"Sylvetsky","year":"2013"},{"key":"2025011710152611500_ref5","doi-asserted-by":"publisher","first-page":"145","DOI":"10.1016\/j.rbmo.2017.11.004","article-title":"Is there an association between artificial sweetener consumption and assisted reproduction outcomes?","volume":"36","author":"Setti","year":"2018","journal-title":"Reprod Biomed Online"},{"key":"2025011710152611500_ref6","doi-asserted-by":"publisher","first-page":"G735","DOI":"10.1152\/ajpgi.90708.2008","article-title":"Effect of the artificial sweetener, sucralose, on gastric emptying and incretin hormone release in healthy subjects","volume":"296","author":"Ma","year":"2009","journal-title":"Am J Physiol Gastrointest Liver Physiol"},{"key":"2025011710152611500_ref7","doi-asserted-by":"publisher","first-page":"508","DOI":"10.1038\/ejcn.2010.291","article-title":"Effects of oral ingestion of sucralose on gut hormone response and appetite in healthy normal-weight subjects","volume":"65","author":"Ford","year":"2011","journal-title":"Eur J Clin Nutr"},{"key":"2025011710152611500_ref8","doi-asserted-by":"publisher","first-page":"367","DOI":"10.1016\/0278-6915(94)00149-I","article-title":"\u03b2-Cyclodextrin: 52-week toxicity studies in the rat and dog","volume":"33","author":"Bellringer","year":"1995","journal-title":"Food Chem Toxicol"},{"key":"2025011710152611500_ref9","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.bbr.2012.04.024","article-title":"Experience with the high-intensity sweetener saccharin impairs glucose homeostasis and GLP-1 release in rats","volume":"233","author":"Swithers","year":"2012","journal-title":"Behav Brain Res"},{"key":"2025011710152611500_ref10","doi-asserted-by":"publisher","first-page":"332","DOI":"10.1016\/j.yrtph.2018.01.009","article-title":"Systematic review and evaluation of aspartame carcinogenicity bioassays using quality criteria","volume":"103","author":"Haighton","year":"2018","journal-title":"Regul Toxicol Pharmacol"},{"key":"2025011710152611500_ref11","doi-asserted-by":"publisher","first-page":"450","DOI":"10.1016\/j.physbeh.2015.06.024","article-title":"Metabolic effects of non-nutritive sweeteners","volume":"152","author":"Pepino","year":"2015","journal-title":"Physiol Behav"},{"key":"2025011710152611500_ref12","doi-asserted-by":"publisher","first-page":"1320","DOI":"10.1017\/S000711451000512X","article-title":"Effects of carbohydrate sugars and artificial sweeteners on appetite and the secretion of gastrointestinal satiety peptides","volume":"105","author":"Steinert","year":"2011","journal-title":"Br J Nutr"},{"key":"2025011710152611500_ref13","doi-asserted-by":"publisher","first-page":"3057","DOI":"10.1039\/c2ay05950a","article-title":"Artificial sweeteners as emerging pollutants in the environment: analytical methodologies and environmental impact","volume":"4","author":"Kokotou","year":"2012","journal-title":"Anal Methods"},{"key":"2025011710152611500_ref14","doi-asserted-by":"publisher","first-page":"151","DOI":"10.1016\/B978-0-12-822503-5.00017-5","volume-title":"Microbial ecology of wastewater treatment plants","author":"Yadav","year":"2021"},{"key":"2025011710152611500_ref15","doi-asserted-by":"publisher","first-page":"816","DOI":"10.1016\/j.scitotenv.2017.10.241","article-title":"Pharmaceuticals and personal care products (PPCPs) and artificial sweeteners (ASs) in surface and ground waters and their application as indication of wastewater contamination","volume":"616\u2013617","author":"Yang","year":"2018","journal-title":"Sci Total Environ"},{"key":"2025011710152611500_ref16","doi-asserted-by":"publisher","first-page":"379","DOI":"10.1007\/698_2017_59","volume-title":"Electro-Fenton process","year":"2017"},{"key":"2025011710152611500_ref17","doi-asserted-by":"publisher","first-page":"2840","DOI":"10.1021\/ci300400a","article-title":"In silico prediction of chemical Ames mutagenicity","volume":"52","author":"Xu","year":"2012","journal-title":"J Chem Inf Model"},{"key":"2025011710152611500_ref18","doi-asserted-by":"publisher","first-page":"325","DOI":"10.1089\/aivt.2017.0019","article-title":"Advanced toxicological risk assessment by implementation of ontologies operationalized in computational models","volume":"3","author":"Staal","year":"2017","journal-title":"Appl Vitr Toxicol"},{"key":"2025011710152611500_ref19","doi-asserted-by":"publisher","first-page":"99","DOI":"10.1007\/978-1-62703-059-5_5","article-title":"Classification models for safe drug molecules","volume":"930","author":"Madan","year":"2013","journal-title":"Methods Mol Biol"},{"key":"2025011710152611500_ref20","doi-asserted-by":"publisher","first-page":"3157","DOI":"10.1007\/s00204-016-1924-3","article-title":"Use of in silico models for prioritization of heat-induced food contaminants in mutagenicity and carcinogenicity testing","volume":"91","author":"Frenzel","year":"2017","journal-title":"Arch Toxicol"},{"key":"2025011710152611500_ref21","doi-asserted-by":"publisher","first-page":"273","DOI":"10.1007\/s13353-014-0198-9","article-title":"Antimutagenic compounds and their possible mechanisms of action","volume":"55","author":"S\u0142oczy\u0144ska","year":"2014","journal-title":"J Appl Genet"},{"key":"2025011710152611500_ref22","doi-asserted-by":"publisher","first-page":"116","DOI":"10.3923\/rjmp.2011.116.126","article-title":"Natural Antimutagens: a review","volume":"5","author":"Bhattacharya","year":"2011","journal-title":"Res J Med Plant"},{"key":"2025011710152611500_ref23","doi-asserted-by":"publisher","first-page":"38","DOI":"10.3389\/fphar.2013.00038","article-title":"Lazar: a modular predictive toxicology framework","volume":"4","author":"Maunz","year":"2013","journal-title":"Front Pharmacol"},{"key":"2025011710152611500_ref24","doi-asserted-by":"publisher","first-page":"4066","DOI":"10.1021\/acs.jmedchem.5b00104","article-title":"pkCSM: predicting small-molecule pharmacokinetic and toxicity properties using graph-based signatures","volume":"58","author":"Pires","year":"2015","journal-title":"J Med Chem"},{"key":"2025011710152611500_ref25","doi-asserted-by":"publisher","first-page":"147","DOI":"10.1007\/s11030-005-9001-5","article-title":"Lazy structure-activity relationships (lazar) for the prediction of rodent carcinogenicity and salmonella mutagenicity","volume":"10","author":"Helma","year":"2006","journal-title":"Mol Divers"},{"key":"2025011710152611500_ref26","doi-asserted-by":"publisher","first-page":"495","DOI":"10.1080\/10629360802083871","article-title":"An evaluation of the implementation of the Cramer classification scheme in the Toxtree software","volume":"19","author":"Patlewicz","year":"2008","journal-title":"SAR QSAR Environ Res"},{"key":"2025011710152611500_ref27","first-page":"48","article-title":"A novel approach: chemical relational databases, and the role of the ISSCAN database on assessing chemical carcinogenicity","volume":"44","author":"Benigni","year":"2008","journal-title":"Ann Ist Super Sanita"},{"key":"2025011710152611500_ref28","first-page":"144","article-title":"Evaluation of nano-formulated heteroleptic metal complexes as potential antifungals against Fusarium oxysporum","volume":"10","author":"Gumber","year":"2018","journal-title":"Der Pharma Chemica"},{"key":"2025011710152611500_ref29","doi-asserted-by":"publisher","first-page":"D380","DOI":"10.1093\/nar\/gkv1277","article-title":"STITCH 5: augmenting protein-chemical interaction networks with tissue and affinity data","volume":"44","author":"Szklarczyk","year":"2016","journal-title":"Nucleic Acids Res"},{"key":"2025011710152611500_ref30","doi-asserted-by":"publisher","first-page":"623","DOI":"10.1021\/acs.jproteome.8b00702","article-title":"Cytoscape StringApp: network analysis and visualization of proteomics data","volume":"18","author":"Doncheva","year":"2019","journal-title":"J Proteome Res"},{"key":"2025011710152611500_ref31","doi-asserted-by":"publisher","first-page":"599","DOI":"10.1093\/chemse\/bjj065","article-title":"Variation in the human TAS1R taste receptor genes","volume":"31","author":"Kim","year":"2006","journal-title":"Chem Senses"},{"key":"2025011710152611500_ref32","doi-asserted-by":"publisher","first-page":"716","DOI":"10.1111\/j.1365-2982.2007.00923","article-title":"Effects of glucagon-like peptide-1 and sympathetic stimulation on gastric accommodation in humans","volume":"19","author":"Andrews","year":"2007","journal-title":"Neurogastroenterol Motil"},{"key":"2025011710152611500_ref33","volume-title":"The new chemistry: food chemistry.","author":"Newton","year":"2007:224"},{"key":"2025011710152611500_ref34","doi-asserted-by":"publisher","first-page":"S11","DOI":"10.1016\/j.fct.2008.04.04","article-title":"Subchronic toxicity of rebaudioside A","volume":"46","author":"Curry","year":"2008","journal-title":"Food Chem Toxicol"}],"container-title":["Toxicology Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/toxres\/article-pdf\/14\/1\/tfaf008\/61477005\/tfaf008.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/toxres\/article-pdf\/14\/1\/tfaf008\/61477005\/tfaf008.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,1,17]],"date-time":"2025-01-17T10:15:37Z","timestamp":1737108937000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/toxres\/article\/doi\/10.1093\/toxres\/tfaf008\/7959284"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,12,31]]},"references-count":34,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2024,12,31]]}},"URL":"https:\/\/doi.org\/10.1093\/toxres\/tfaf008","relation":{},"ISSN":["2045-4538"],"issn-type":[{"value":"2045-4538","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2025,2]]},"published":{"date-parts":[[2024,12,31]]},"article-number":"tfaf008"}}