{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,13]],"date-time":"2026-05-13T17:03:34Z","timestamp":1778691814115,"version":"3.51.4"},"reference-count":26,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2006,10,5]],"date-time":"2006-10-05T00:00:00Z","timestamp":1160006400000},"content-version":"vor","delay-in-days":34,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Annals of the New York Academy of Sciences"],"published-print":{"date-parts":[[2006,9]]},"abstract":"<jats:p><jats:bold><jats:sc>Abstract:\u2002<\/jats:sc><\/jats:bold>  <jats:bold>Aspartame (APM) is one of the most widely used artificial sweeteners in the world. Its ever\u2010growing use in more than 6000 products, such as soft drinks, chewing gum, candy, desserts, etc., has been accompanied by rising consumer concerns regarding its safety, in particular its potential long\u2010term carcinogenic effects. In light of the inadequacy of the carcinogenicity bioassays performed in the 1970s and 1980s, a long\u2010term mega\u2010experiment on APM was undertaken at the Cesare Maltoni Cancer Research Center of the European Ramazzini Foundation on groups of male and female Sprague\u2010Dawley rats (100\u2013150\/sex\/group), 8 weeks old at the start of the experiment. APM was administered in feed at concentrations of 100,000, 50,000, 10,000, 2,000, 400, 80, or 0 ppm. Treatment lasted until spontaneous death of the animals. The results of the study demonstrate that APM causes: (<jats:italic>a<\/jats:italic>) an increased incidence of malignant tumor\u2010bearing animals, with a positive significant trend in both sexes, and in particular in females treated at 50,000 ppm (<jats:italic>P<\/jats:italic>\u2264 0.01) when compared to controls; (<jats:italic>b<\/jats:italic>) an increase in lymphomas\u2013leukemias, with a positive significant trend in both sexes, and in particular in females treated at doses of 100,000 (<jats:italic>P<\/jats:italic>\u2264 0.01), 50,000 (<jats:italic>P<\/jats:italic>\u2264 0.01), 10,000 (<jats:italic>P<\/jats:italic>\u2264 0.05), 2000 (<jats:italic>P<\/jats:italic>\u2264 0.05), and 400 ppm (<jats:italic>P<\/jats:italic>\u2264 0.01); (<jats:italic>c<\/jats:italic>) a statistically significant increased incidence, with a positive significant trend, of transitional cell carcinomas of the renal pelvis and ureter in females and particularly in those treated at 100,000 ppm (<jats:italic>P<\/jats:italic>\u2264 0.05); and (<jats:italic>d<\/jats:italic>) an increased incidence of malignant schwannomas of the peripheral nerves, with a positive trend in males (<jats:italic>P<\/jats:italic>\u2264 0.05). The results of this mega\u2010experiment indicate that APM, in the tested experimental conditions, is a multipotential carcinogenic agent.<\/jats:bold> <\/jats:p>","DOI":"10.1196\/annals.1371.080","type":"journal-article","created":{"date-parts":[[2006,11,22]],"date-time":"2006-11-22T03:36:57Z","timestamp":1164166617000},"page":"559-577","source":"Crossref","is-referenced-by-count":49,"title":["Results of Long\u2010Term Carcinogenicity Bioassay on Sprague\u2010Dawley Rats Exposed to Aspartame Administered in Feed"],"prefix":"10.1111","volume":"1076","author":[{"given":"FIORELLA","family":"BELPOGGI","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"MORANDO","family":"SOFFRITTI","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"MICHELA","family":"PADOVANI","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"DAVIDE DEGLI","family":"ESPOSTI","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"MICHELINA","family":"LAURIOLA","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"FRANCO","family":"MINARDI","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2006,10,5]]},"reference":[{"key":"e_1_2_7_2_2","doi-asserted-by":"publisher","DOI":"10.1159\/000059697"},{"key":"e_1_2_7_3_2","doi-asserted-by":"publisher","DOI":"10.1159\/000059701"},{"key":"e_1_2_7_4_2","doi-asserted-by":"publisher","DOI":"10.1093\/annonc\/mdh256"},{"key":"e_1_2_7_5_2","doi-asserted-by":"publisher","DOI":"10.1006\/rtph.2002.1542"},{"key":"e_1_2_7_6_2","first-page":"3","volume-title":"Aspartame Physiology and Biochemistry.","author":"Mazur R.H.","year":"1984"},{"key":"e_1_2_7_7_2","doi-asserted-by":"publisher","DOI":"10.1159\/000059691"},{"key":"e_1_2_7_8_2","unstructured":"U.S.National Library of Medicine.2006.Hazardous Substances Data Bank.http:\/\/toxnet.nlm.nih.gov\/[accessed 10 May 2005."},{"key":"e_1_2_7_9_2","unstructured":"USAFood Navigator.http:\/\/www.foodnavigator\u2010usa.com\/news\/printNewsBis.asp?id=59163. 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Pharmacol."},{"key":"e_1_2_7_12_2","doi-asserted-by":"publisher","DOI":"10.1080\/15287397609529445"},{"key":"e_1_2_7_13_2","first-page":"47","volume-title":"In Aspartame Physiology and Biochemistry","author":"Stegink L.D.","year":"1984"},{"key":"e_1_2_7_14_2","first-page":"77","volume-title":"In Aspartame Physiology and Biochemistry.","author":"Harper A.E.","year":"1984"},{"key":"e_1_2_7_15_2","first-page":"141","volume-title":"In Aspartame Physiology and Biochemistry.","author":"Opperman J.A.","year":"1984"},{"key":"e_1_2_7_16_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0278-6915(99)00163-5"},{"key":"e_1_2_7_17_2","doi-asserted-by":"publisher","DOI":"10.1081\/DCT-120037506"},{"key":"e_1_2_7_18_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0278-6915(99)00115-5"},{"key":"e_1_2_7_19_2","unstructured":"National Toxicology Program.2005.Toxicology studies of aspartame (CAS No. 22839\u201047\u20100) in genetically modified (FVB Tg.AC hemizygous) and B6.129\u2010Cdkn2atm1Rdp(N2) deficient mice and carcinogenicity studies on aspartame in genetically modified B6.129\u2010Trp53tm1Brd(N5) haploinsufficient mice (feed studies). Genetically Modified Model Report NTP GMM1:5\u201366."},{"key":"e_1_2_7_20_2","doi-asserted-by":"publisher","DOI":"10.1097\/00005072-199611000-00002"},{"key":"e_1_2_7_21_2","first-page":"38285","article-title":"Aspartame: Commissioner's final decision","volume":"46","author":"U.S. Food and Drug Administration","year":"1981","journal-title":"Fed. Regist."},{"key":"e_1_2_7_22_2","doi-asserted-by":"publisher","DOI":"10.1016\/0378-4274(81)90089-8"},{"key":"e_1_2_7_23_2","doi-asserted-by":"publisher","DOI":"10.1016\/0300-483X(81)90119-0"},{"key":"e_1_2_7_24_2","doi-asserted-by":"publisher","DOI":"10.1289\/ehp.8711"},{"key":"e_1_2_7_25_2","first-page":"107","article-title":"Aspartame induces lymphomas and leukaemias in rats","volume":"10","author":"Soffritti M.","year":"2005","journal-title":"Eur. J. 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