{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,18]],"date-time":"2026-10-18T10:11:17Z","timestamp":1792318277183,"version":"4.4.0"},"reference-count":46,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2013,6,1]],"date-time":"2013-06-01T00:00:00Z","timestamp":1370044800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2013,6,1]],"date-time":"2013-06-01T00:00:00Z","timestamp":1370044800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"}],"content-domain":{"domain":["elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Food and Chemical Toxicology"],"published-print":{"date-parts":[[2013,6]]},"DOI":"10.1016\/j.fct.2013.02.021","type":"journal-article","created":{"date-parts":[[2013,2,28]],"date-time":"2013-02-28T17:02:08Z","timestamp":1362070928000},"page":"214-222","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":9,"special_numbering":"C","title":["Ninety-day dietary toxicity study of apple polyphenol extracts in Crl: CD (SD) rats"],"prefix":"10.1016","volume":"56","author":[{"given":"Kyoko","family":"Fujiwara","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shohei","family":"Nakashima","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manabu","family":"Sami","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tomomasa","family":"Kanda","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.fct.2013.02.021_b0005","first-page":"893","article-title":"Evaluation of safety of excessive intake and efficacy of long-term intake of beverage containing polyphenols derived from apples","volume":"33","author":"Akazome","year":"2005","journal-title":"Jpn. Pharmacol. Ther."},{"key":"10.1016\/j.fct.2013.02.021_b0010","doi-asserted-by":"crossref","first-page":"1370","DOI":"10.1248\/bpb.23.1370","article-title":"Antiallergic effect of apple polyphenols on the allergic model mouse","volume":"23","author":"Akiyama","year":"2000","journal-title":"Biol. Pharm. Bull."},{"key":"10.1016\/j.fct.2013.02.021_b0015","doi-asserted-by":"crossref","first-page":"4485","DOI":"10.1016\/j.febslet.2005.07.019","article-title":"Dietary unripe apple polyphenol inhibits the development of food allergies in murine models","volume":"579","author":"Akiyama","year":"2005","journal-title":"FEBS Lett."},{"key":"10.1016\/j.fct.2013.02.021_b0020","doi-asserted-by":"crossref","first-page":"1731","DOI":"10.1016\/S0278-6915(02)00155-2","article-title":"Subchronic 3-month oral toxicity study of grape seed and grape skin extracts","volume":"40","author":"Bentivegna","year":"2002","journal-title":"Food Chem. Toxicol."},{"key":"10.1016\/j.fct.2013.02.021_b0025","doi-asserted-by":"crossref","first-page":"209","DOI":"10.1016\/0030-4220(72)90411-2","article-title":"Enlargement of salivary glands","volume":"34","author":"Buchner","year":"1972","journal-title":"Oral Surg."},{"key":"10.1016\/j.fct.2013.02.021_b0030","doi-asserted-by":"crossref","first-page":"429","DOI":"10.1016\/S0278-6915(00)00018-1","article-title":"Toxicity and mutagenicity studies of DN-50000\u00ae and RP-1\u00ae enzymes","volume":"38","author":"Burdock","year":"2000","journal-title":"Food Chem. Toxicol."},{"key":"10.1016\/j.fct.2013.02.021_b0035","doi-asserted-by":"crossref","first-page":"2407","DOI":"10.1016\/j.fct.2009.06.036","article-title":"90-Day feeding and genotoxicity studies on a refined arachidonic acid-rich oil","volume":"47","author":"Casterton","year":"2009","journal-title":"Food Chem. Toxicol."},{"key":"10.1016\/j.fct.2013.02.021_b0040","first-page":"283","article-title":"Clinical effects of apple polyphenols on persistent allergic rhinitis: a randomized double-blind placebo-controlled parallel arm study","volume":"16","author":"Enomoto","year":"2006","journal-title":"J. Invest. Allergol. Clin. Immunol."},{"key":"10.1016\/j.fct.2013.02.021_b0045","doi-asserted-by":"crossref","first-page":"1156","DOI":"10.1021\/jf960493k","article-title":"Catechin and procyanidin composition of seeds from grape cultivars grown in Ontario","volume":"45","author":"Fuleki","year":"1997","journal-title":"J. Agri. Food Chem."},{"key":"10.1016\/j.fct.2013.02.021_b0050","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1016\/S0278-6915(00)00028-4","article-title":"Acute and subchronic toxicity of sucralose","volume":"38","author":"Goldsmith","year":"2000","journal-title":"Food Chem. Toxicol."},{"key":"10.1016\/j.fct.2013.02.021_b0055","doi-asserted-by":"crossref","first-page":"1291","DOI":"10.1093\/carcin\/bgi074","article-title":"Chemopreventive properties of apple procyanidins on human colon cancer-derived metastatic SW620 cells and in a rat model of colon carcinogenesis","volume":"26","author":"Goss\u00e9","year":"2005","journal-title":"Carcinogenesis"},{"key":"10.1016\/j.fct.2013.02.021_b0060","first-page":"795","article-title":"Induction of apoptosis by three types of procyanidin isolated from apple (Rosaceae Malus pumila) in human stomach cancer KATO III cells","volume":"13","author":"Hibasami","year":"2004","journal-title":"Int. J. Mol. Med."},{"key":"10.1016\/j.fct.2013.02.021_b0065","doi-asserted-by":"crossref","first-page":"1231","DOI":"10.1016\/j.fct.2006.12.030","article-title":"Thirteen-week repeated dose toxicity of Siraitia grosvenori extract in Wistar Hannover (GALAS) rats","volume":"45","author":"Jin","year":"2007","journal-title":"Food Chem. Toxicol."},{"key":"10.1016\/j.fct.2013.02.021_b0070","doi-asserted-by":"crossref","first-page":"1284","DOI":"10.1271\/bbb.62.1284","article-title":"Inhibitory effects of apple polyphenol on induced histamine release from RBL-2H3 cells and rat mast cells","volume":"62","author":"Kanda","year":"1998","journal-title":"Biosci. Biotechnol. Biochem."},{"key":"10.1016\/j.fct.2013.02.021_b0075","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1016\/j.fct.2010.10.011","article-title":"Subchronic oral toxicity assessment of N-acetyl-L-aspartic acid in rats","volume":"49","author":"Karaman","year":"2011","journal-title":"Food Chem. Toxicol."},{"key":"10.1016\/j.fct.2013.02.021_b0080","doi-asserted-by":"crossref","first-page":"1863","DOI":"10.1021\/jf990534n","article-title":"Matrix-assisted laser desorption\/ionization time-of-flight mass spectrometry of polygalloyl polyflavan-3-ols in grape seed extract","volume":"48","author":"Krueger","year":"2000","journal-title":"J. Agric. Food Chem."},{"key":"10.1016\/j.fct.2013.02.021_b0085","doi-asserted-by":"crossref","first-page":"3156","DOI":"10.1021\/jf011522g","article-title":"Can apple antioxidants inhibit tumor cell proliferation? Generation of H2O2 during interaction of phenolic compounds with cell culture media","volume":"50","author":"Lapidot","year":"2002","journal-title":"J. Agric. Food Chem."},{"key":"10.1016\/j.fct.2013.02.021_b0090","doi-asserted-by":"crossref","first-page":"603","DOI":"10.1016\/S0955-2863(02)00206-1","article-title":"Comparative content of some bioactive compounds in apples, peaches, and pears and their influence on lipids and antioxidant capacity in rats","volume":"13","author":"Leontowicz","year":"2002","journal-title":"J. Nutr. Biochem."},{"key":"10.1016\/j.fct.2013.02.021_b0095","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1002\/jsfa.2740640204","article-title":"Developmental changes in the concentration and composition of flavonoids in skin of a red and a green apple cultivar","volume":"64","author":"Lister","year":"1994","journal-title":"J. Sci. Food Agri."},{"key":"10.1016\/j.fct.2013.02.021_b0100","doi-asserted-by":"crossref","first-page":"4046","DOI":"10.1021\/jf9903197","article-title":"Study of the phenolic profile of cider apple cultivars at maturity by multivariate techniques","volume":"47","author":"Mangas","year":"1999","journal-title":"J. Agri. Food Chem."},{"key":"10.1016\/j.fct.2013.02.021_b0105","doi-asserted-by":"crossref","first-page":"585","DOI":"10.1093\/carcin\/bgm198","article-title":"Apple procyanidins induce tumor cell apoptosis through mitochondrial pathway activation of caspase-3","volume":"29","author":"Miura","year":"2008","journal-title":"Carcinogenesis"},{"key":"10.1016\/j.fct.2013.02.021_b0110","doi-asserted-by":"crossref","first-page":"143","DOI":"10.5650\/jos.54.143","article-title":"Serum cholesterol-lowering effect of apple polyphenols in healthy subjects","volume":"54","author":"Nagasako-Akazome","year":"2005","journal-title":"J. Oleo Sci."},{"key":"10.1016\/j.fct.2013.02.021_b0115","first-page":"82","article-title":"Efficacy of suppression on postprandial serum triglyceride elevation with apple polyphenols","volume":"14","author":"Nagasako-Akazome","year":"2007","journal-title":"Jpn. J. Food Chem."},{"key":"10.1016\/j.fct.2013.02.021_b0120","doi-asserted-by":"crossref","first-page":"213","DOI":"10.1159\/000142044","article-title":"Procyanidin C1 from apple extracts inhibits Fc epsilon RI-mediated mast cell activation","volume":"147","author":"Nakano","year":"2008","journal-title":"Int. Arch. Allergy Immunol."},{"key":"10.1016\/j.fct.2013.02.021_b0125","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1007\/s11745-006-3008-2","article-title":"Absorption of dietary cholesterol oxidation products and their downstream metabolic effects are reduced by dietary apple polyphenols","volume":"42","author":"Ogino","year":"2007","journal-title":"Lipids"},{"key":"10.1016\/j.fct.2013.02.021_b0130","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1002\/(SICI)1097-0231(19970115)11:1<31::AID-RCM784>3.0.CO;2-T","article-title":"Identification of catechin oligomer from apple (Malus pumila cv. Fuji) in matrix-assisted laser desorption\/ionization time-of-flight mass spectrometry and fast-atom bombardment mass spectrometry","volume":"11","author":"Ohnishi-Kameyama","year":"1997","journal-title":"Rapid Commun. Mass Spectrom."},{"key":"10.1016\/j.fct.2013.02.021_b0135","doi-asserted-by":"crossref","first-page":"79","DOI":"10.5650\/jos.55.79","article-title":"Effects of dietary procyanidins and tea polyphenols on adipose tissue mass and fatty acid metabolism in rats on a high fat diet","volume":"55","author":"Osada","year":"2006","journal-title":"J. Oleo Sci."},{"key":"10.1016\/j.fct.2013.02.021_b0140","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1016\/0308-8146(95)90788-9","article-title":"Comparative flavan-3-ol composition of seeds from different grape varieties","volume":"53","author":"Santos-Buelga","year":"1995","journal-title":"Food Chem."},{"key":"10.1016\/j.fct.2013.02.021_b0145","doi-asserted-by":"crossref","first-page":"413","DOI":"10.1002\/mnfr.200500194","article-title":"Modulation of oxidative cell damage by reconstituted mixtures of phenolic apple juice extracts in human colon cell lines","volume":"50","author":"Schaefer","year":"2006","journal-title":"Mol. Nutr. Food Res."},{"key":"10.1016\/j.fct.2013.02.021_b0150","series-title":"Food Phenolics","author":"Shahidi","year":"1995"},{"key":"10.1016\/j.fct.2013.02.021_b0155","doi-asserted-by":"crossref","first-page":"3806","DOI":"10.1021\/jf0300184","article-title":"Isolation and structural elucidation of some procyanidins from apple by low-temperature NMR","volume":"51","author":"Shoji","year":"2003","journal-title":"J. Agri. Food Chem."},{"key":"10.1016\/j.fct.2013.02.021_b0160","doi-asserted-by":"crossref","first-page":"959","DOI":"10.1016\/j.fct.2004.02.008","article-title":"The toxicology and safety of apple polyphenol extract","volume":"42","author":"Shoji","year":"2004","journal-title":"Food Chem. Toxicol."},{"key":"10.1016\/j.fct.2013.02.021_b0165","doi-asserted-by":"crossref","first-page":"206","DOI":"10.1016\/j.chroma.2005.10.065","article-title":"Apple (Malus pumila) procyanidins fractionated according to the degree of polymerization using normal-phase chromatography and characterized by HPLC-ESI\/MS and MALDI-TOF\/MS","volume":"1102","author":"Shoji","year":"2006","journal-title":"J. Chromatogr."},{"key":"10.1016\/j.fct.2013.02.021_b0170","doi-asserted-by":"crossref","first-page":"884","DOI":"10.1021\/jf052260b","article-title":"Apple procyanidin oligomers absorption in rats after oral administration: analysis of procyanidins in plasma using the porter method and high-performance liquid chromatography\/tandem mass spectrometry","volume":"54","author":"Shoji","year":"2006","journal-title":"J. Agric. Food Chem."},{"key":"10.1016\/j.fct.2013.02.021_b0175","doi-asserted-by":"crossref","first-page":"1572","DOI":"10.1021\/jf00097a031","article-title":"Influence of processing and storage on the phenolic composition of apple juice","volume":"38","author":"Spanos","year":"1990","journal-title":"J. Agri. Food Chem."},{"key":"10.1016\/j.fct.2013.02.021_b0180","doi-asserted-by":"crossref","first-page":"461","DOI":"10.1002\/(SICI)1097-0010(199812)78:4<461::AID-JSFA138>3.0.CO;2-K","article-title":"Changes in phenolic composition of apple juices by HPLC with direct injection","volume":"78","author":"Su\u00e1rez","year":"1998","journal-title":"J. Sci. Food Agri."},{"key":"10.1016\/j.fct.2013.02.021_b0185","doi-asserted-by":"crossref","first-page":"4604","DOI":"10.1021\/jf070569k","article-title":"Oligomeric procyanidins in apple polyphenol are main active components for inhibition of pancreatic lipase and triglyceride absorption","volume":"55","author":"Sugiyama","year":"2007","journal-title":"J. Agric. Food Chem."},{"key":"10.1016\/j.fct.2013.02.021_b0190","doi-asserted-by":"crossref","first-page":"122","DOI":"10.1055\/s-0030-1250204","article-title":"Procyanidins from apples (Malus pumila Mill.) extend the lifespan of Caenorhabditis elegans","volume":"77","author":"Sunagawa","year":"2011","journal-title":"Planta. Med."},{"key":"10.1016\/j.fct.2013.02.021_b0195","doi-asserted-by":"crossref","first-page":"2789","DOI":"10.1016\/j.fct.2008.05.013","article-title":"Toxic effects of L-aspartic acid at high dose levels on kidneys and salivary glands in Fischer 344 rats detected in a 90-day feeding study","volume":"46","author":"Tada","year":"2008","journal-title":"Food Chem. Toxicol."},{"key":"10.1016\/j.fct.2013.02.021_b0200","doi-asserted-by":"crossref","first-page":"2224","DOI":"10.1016\/j.fct.2008.02.023","article-title":"Evaluation of toxicity of green tea catechins with 90-day dietary administration to F344 rats","volume":"46","author":"Takami","year":"2008","journal-title":"Food Chem. Toxicol."},{"key":"10.1016\/j.fct.2013.02.021_b0205","first-page":"63","article-title":"13-Week oral toxicity of guarana extract in F344\/DuCrj rats","volume":"12","author":"Tamano","year":"2005","journal-title":"Jpn. J. Food Chem."},{"key":"10.1016\/j.fct.2013.02.021_b0210","doi-asserted-by":"crossref","first-page":"275","DOI":"10.3109\/10408448209037495","article-title":"The toxicology of cocoa and methylxanthines: a review of the literature","volume":"9","author":"Tarka","year":"1982","journal-title":"Crit. Rev. Toxicol."},{"key":"10.1016\/j.fct.2013.02.021_b0215","doi-asserted-by":"crossref","first-page":"1117","DOI":"10.1152\/ajplegacy.1963.205.6.1117","article-title":"Submandibular salivary gland enlargement by feeding pancreatin to rats","volume":"205","author":"Wells","year":"1963","journal-title":"Am. J. Physiol."},{"key":"10.1016\/j.fct.2013.02.021_b0220","doi-asserted-by":"crossref","first-page":"247","DOI":"10.1152\/ajplegacy.1967.212.2.247","article-title":"Functional hyper-trophy and atrophy of the salivary glands of rats","volume":"212","author":"Wells","year":"1966","journal-title":"Am. J. Physiol."},{"key":"10.1016\/j.fct.2013.02.021_b0225","doi-asserted-by":"crossref","first-page":"2180","DOI":"10.1021\/jf011066w","article-title":"90-Day oral toxicity study of a grape seed extract (IH636) in rats","volume":"50","author":"Wren","year":"2002","journal-title":"J. Agric. Food Chem."},{"key":"10.1016\/j.fct.2013.02.021_b0230","doi-asserted-by":"crossref","first-page":"599","DOI":"10.1016\/S0278-6915(02)00006-6","article-title":"Safety evaluation of proanthocyanidin-rich extract from grape seeds","volume":"40","author":"Yamakoshi","year":"2002","journal-title":"Food Chem. Toxicol."}],"container-title":["Food and Chemical Toxicology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0278691513001300?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0278691513001300?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2025,10,3]],"date-time":"2025-10-03T21:12:42Z","timestamp":1759525962000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0278691513001300"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2013,6]]},"references-count":46,"alternative-id":["S0278691513001300"],"URL":"https:\/\/doi.org\/10.1016\/j.fct.2013.02.021","relation":{},"ISSN":["0278-6915"],"issn-type":[{"value":"0278-6915","type":"print"}],"subject":[],"published":{"date-parts":[[2013,6]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Ninety-day dietary toxicity study of apple polyphenol extracts in Crl: CD (SD) rats","name":"articletitle","label":"Article Title"},{"value":"Food and Chemical Toxicology","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.fct.2013.02.021","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"Copyright \u00a9 2013 Elsevier Ltd. All rights reserved.","name":"copyright","label":"Copyright"}]}}