{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,14]],"date-time":"2026-09-14T12:05:29Z","timestamp":1789387529839,"version":"build-2803163510"},"reference-count":58,"publisher":"Elsevier BV","issue":"1","license":[{"start":{"date-parts":[[2011,1,1]],"date-time":"2011-01-01T00:00:00Z","timestamp":1293840000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2011,1,1]],"date-time":"2011-01-01T00:00:00Z","timestamp":1293840000000},"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":[[2011,1]]},"DOI":"10.1016\/j.fct.2010.10.011","type":"journal-article","created":{"date-parts":[[2010,10,13]],"date-time":"2010-10-13T07:25:24Z","timestamp":1286954724000},"page":"155-165","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":13,"title":["Subchronic oral toxicity assessment of N-acetyl-l-aspartic acid in rats"],"prefix":"10.1016","volume":"49","author":[{"given":"Sule","family":"Karaman","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John Barnett","family":"Jr.","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Greg P.","family":"Sykes","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bryan","family":"Delaney","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.fct.2010.10.011_b0005","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1016\/S0006-8993(00)02028-X","article-title":"Epileptic seizures induced by N-acetyl-l-aspartate in rats: in vivo and in vitro studies","volume":"861","author":"Akimitsu","year":"2000","journal-title":"Brain Res."},{"key":"10.1016\/j.fct.2010.10.011_b0010","doi-asserted-by":"crossref","first-page":"941","DOI":"10.1023\/A:1023250721185","article-title":"N-acetylaspartate in the vertebrate brain: metabolism and function","volume":"28","author":"Baslow","year":"2003","journal-title":"Neurochem. Res."},{"key":"10.1016\/j.fct.2010.10.011_b0015","doi-asserted-by":"crossref","first-page":"783","DOI":"10.1139\/o66-096","article-title":"Metabolism of N-acetyl-l-aspartic acid in mice","volume":"44","author":"Berlinguet","year":"1966","journal-title":"Can. J. Biochem."},{"key":"10.1016\/j.fct.2010.10.011_b0020","doi-asserted-by":"crossref","first-page":"209","DOI":"10.1016\/0030-4220(72)90411-2","article-title":"Enlargement of salivary glands. Review of the literature","volume":"34","author":"Buchner","year":"1972","journal-title":"Oral Surg. Oral Med. Oral Pathol."},{"key":"10.1016\/j.fct.2010.10.011_b0025","doi-asserted-by":"crossref","first-page":"429","DOI":"10.1016\/S0278-6915(00)00018-1","article-title":"Toxicity and mutagenicity studies of DN-50000((R)) and RP-1((R)) enzymes","volume":"38","author":"Burdock","year":"2000","journal-title":"Food Chem. Toxicol."},{"key":"10.1016\/j.fct.2010.10.011_b0030","doi-asserted-by":"crossref","first-page":"406","DOI":"10.1007\/s004310051102","article-title":"N-acetylaspartylglutamate in Canavan disease: an adverse effector?","volume":"158","author":"Burlina","year":"1999","journal-title":"Eur. J. Pediatr."},{"key":"10.1016\/j.fct.2010.10.011_b0035","doi-asserted-by":"crossref","first-page":"736","DOI":"10.1046\/j.1471-4159.2001.00456.x","article-title":"Intraneuronal N-acetylaspartate supplies acetyl groups for myelin lipid synthesis: evidence for myelin-associated aspartoacylase","volume":"78","author":"Chakraborty","year":"2001","journal-title":"J. Neurochem."},{"key":"10.1016\/j.fct.2010.10.011_b0040","doi-asserted-by":"crossref","first-page":"576","DOI":"10.1177\/00220345570360041401","article-title":"Enlargement of submandibular salivary glands of rats restricted to acidic and basic solutions as the sole source of drinking fluid","volume":"36","author":"Cox","year":"1957","journal-title":"J. Dent. Res."},{"key":"10.1016\/j.fct.2010.10.011_b0045","doi-asserted-by":"crossref","first-page":"599","DOI":"10.1016\/0892-0362(91)90043-V","article-title":"Interlaboratory comparison of motor activity experiments: implication for neurotoxicological assessments","volume":"13","author":"Crofton","year":"1991","journal-title":"Neurotoxicol. Teratol."},{"key":"10.1016\/j.fct.2010.10.011_b0050","doi-asserted-by":"crossref","first-page":"1761","DOI":"10.1016\/j.fct.2010.03.048","article-title":"Acute oral toxicity of N-acetyl-l-aspartic acid (NAA) in rats","volume":"48","author":"Delaney","year":"2010","journal-title":"Food Chem. Toxicol."},{"key":"10.1016\/j.fct.2010.10.011_b0055","doi-asserted-by":"crossref","first-page":"2023","DOI":"10.1016\/j.fct.2008.01.042","article-title":"Acute and repeated dose oral toxicity of N-acetyl-l-aspartic acid in Sprague-Dawley rats","volume":"46","author":"Delaney","year":"2008","journal-title":"Food Chem. Toxicol."},{"key":"10.1016\/j.fct.2010.10.011_b0060","doi-asserted-by":"crossref","first-page":"262","DOI":"10.3181\/00379727-110-27485","article-title":"An orally-active, heat-labile factor in pancreas which induces salivary gland hypertrophy in rats","volume":"110","author":"Ershoff","year":"1962","journal-title":"Proc. Soc. Exp. Biol. Med."},{"key":"10.1016\/j.fct.2010.10.011_b0065","doi-asserted-by":"crossref","first-page":"1049","DOI":"10.1016\/S0300-9084(99)00330-2","article-title":"Distribution and subcellular localization of acylpeptide hydrolase and acylase I along the hog gastro-intestinal tract","volume":"81","author":"Giardina","year":"1999","journal-title":"Biochimie"},{"key":"10.1016\/j.fct.2010.10.011_b0070","doi-asserted-by":"crossref","first-page":"53","DOI":"10.3109\/10915818909009093","article-title":"Development of tier I neurobehavioral testing capabilities for incorporation into pivotal rodent safety assessment studies","volume":"8","author":"Haggerty","year":"1989","journal-title":"J. Am. Coll. Toxicol."},{"key":"10.1016\/j.fct.2010.10.011_b0075","doi-asserted-by":"crossref","first-page":"E1482","DOI":"10.1096\/fj.05-5358fje","article-title":"Aspartoacylase is a regulated nuclear-cytoplasmic enzyme","volume":"20","author":"Hershfield","year":"2006","journal-title":"FASEB J."},{"key":"10.1016\/j.fct.2010.10.011_b0080","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.brainres.2007.02.069","article-title":"Mutational analysis of aspartoacylase: implications for Canavan disease","volume":"1148","author":"Hershfield","year":"2007","journal-title":"Brain Res."},{"key":"10.1016\/j.fct.2010.10.011_b0085","doi-asserted-by":"crossref","first-page":"9121","DOI":"10.1021\/jf801523c","article-title":"N-acetylaspartate and N-acetylglutamate in Soybeans (Glycine max (L.) Merr.), Maize (Zea maize L.) and Other Foodstuffs","volume":"56","author":"Hession","year":"2008","journal-title":"J. Agric. Food Chem."},{"key":"10.1016\/j.fct.2010.10.011_b0090","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1002\/(SICI)1097-0185(19990601)255:2<155::AID-AR5>3.0.CO;2-4","article-title":"Developmental changes of sugar residues and secretory protein in mucous cells of the early postnatal rat parotid gland","volume":"255","author":"Ikeda","year":"1999","journal-title":"Anat. Rec."},{"key":"10.1016\/j.fct.2010.10.011_b0095","doi-asserted-by":"crossref","first-page":"222","DOI":"10.1007\/BF00401402","article-title":"Comprehensive observational assessment: Ia - A systematic, quantitative procedure for assessing the behavioral and physiologic state of the mouse","volume":"13","author":"Irwin","year":"1968","journal-title":"Psychopharmacologia"},{"key":"10.1016\/j.fct.2010.10.011_b0100","doi-asserted-by":"crossref","first-page":"691","DOI":"10.1177\/00220345820610051401","article-title":"Effects of increasing the bulk content of the diet on the rat parotid gland and the saliva","volume":"61","author":"Johnson","year":"1982","journal-title":"J. Dent. Res."},{"key":"10.1016\/j.fct.2010.10.011_b0105","doi-asserted-by":"crossref","first-page":"975","DOI":"10.1212\/WNL.18.10.975","article-title":"Spongy degeneration of the brain: a chemical study of two cases including isolation and characterization of myelin","volume":"18","author":"Kamoshita","year":"1968","journal-title":"Neurology"},{"key":"10.1016\/j.fct.2010.10.011_b0110","doi-asserted-by":"crossref","first-page":"1936","DOI":"10.1016\/j.fct.2009.05.005","article-title":"Mutagenicity studies with N-acetyl-l-aspartic acid","volume":"47","author":"Karaman","year":"2009","journal-title":"Food Chem. Toxicol."},{"key":"10.1016\/j.fct.2010.10.011_b0115","doi-asserted-by":"crossref","first-page":"413","DOI":"10.1002\/nbm.845","article-title":"Feeding versus infusion: a novel approach to study the NAA metabolism in rat brain","volume":"16","author":"Karelson","year":"2003","journal-title":"NMR Biomed."},{"key":"10.1016\/j.fct.2010.10.011_b0120","doi-asserted-by":"crossref","first-page":"118","DOI":"10.1038\/ng1093-118","article-title":"Cloning of the human aspartoacylase cDNA and a common missense mutation in Canavan disease","volume":"5","author":"Kaul","year":"1993","journal-title":"Nat. Genet."},{"key":"10.1016\/j.fct.2010.10.011_b0125","doi-asserted-by":"crossref","first-page":"209","DOI":"10.1002\/ar.a.20003","article-title":"Granule types and their morphological changes in terminal cluster and acinar cells in the late pre- and early postnatal rat sublingual gland","volume":"277A","author":"Kikuchi","year":"2004","journal-title":"Anat. Rec. Part A"},{"key":"10.1016\/j.fct.2010.10.011_b0130","doi-asserted-by":"crossref","first-page":"176","DOI":"10.1016\/S0169-328X(02)00490-4","article-title":"Aspartoacylase is restricted primarily to myelin synthesizing cells in the CNS: therapeutic implications for Canavan disease","volume":"107","author":"Kirmani","year":"2002","journal-title":"Brain Res. Mol. Brain Res."},{"key":"10.1016\/j.fct.2010.10.011_b0135","doi-asserted-by":"crossref","first-page":"2512","DOI":"10.1046\/j.1471-4159.2000.0742512.x","article-title":"Accumulation of N-acetyl-l-aspartate in the brain of the tremor rat, a mutant exhibiting absence-like seizure and spongiform degeneration in the central nervous system","volume":"74","author":"Kitada","year":"2000","journal-title":"J. Neurochem."},{"key":"10.1016\/j.fct.2010.10.011_b0290","series-title":"Casarett and Doull\u2019s Toxicology \u2013 The Basic Science of Poisons","first-page":"12","article-title":"Principles of toxicology","author":"Klaassen","year":"1986"},{"key":"10.1016\/j.fct.2010.10.011_b0140","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1002\/mrdd.20108","article-title":"Canavan disease: a white matter disorder","volume":"12","author":"Kumar","year":"2006","journal-title":"Ment. Retard. Dev Disabil. Res. Rev."},{"key":"10.1016\/j.fct.2010.10.011_b0145","doi-asserted-by":"crossref","first-page":"5221","DOI":"10.1073\/pnas.0409184102","article-title":"Defective N-acetylaspartate catabolism reduces brain acetate levels and myelin lipid synthesis in Canavan\u2019s disease","volume":"102","author":"Madhavarao","year":"2005","journal-title":"Proc Natl. Acad. Sci. USA"},{"key":"10.1016\/j.fct.2010.10.011_b0150","unstructured":"MAFF, 1999. Japanese Ministry of Agriculture, Forestry and Fisheries. Good Laboratory Practice Standards. 11 Nousan No. 6283."},{"key":"10.1016\/j.fct.2010.10.011_b0155","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1016\/0169-328X(95)00044-S","article-title":"N-acetylaspartate as an acetyl source in the nervous system","volume":"31","author":"Mehta","year":"1995","journal-title":"Brain Res. Mol. Brain Res."},{"key":"10.1016\/j.fct.2010.10.011_b0160","doi-asserted-by":"crossref","first-page":"804","DOI":"10.1111\/j.1471-4159.1981.tb01665.x","article-title":"A gas chromatographic method for the determination of N-acetyl-l-aspartic acid, N-acetyl-alpha-aspartylglutamic acid and beta-citryl-l-glutamic acid and their distributions in the brain and other organs of various species of animals","volume":"36","author":"Miyake","year":"1981","journal-title":"J. Neurochem."},{"key":"10.1016\/j.fct.2010.10.011_b0165","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1016\/j.pneurobio.2006.12.003","article-title":"N-acetylaspartate in the CNS: from neurodiagnostics to neurobiology","volume":"81","author":"Moffett","year":"2007","journal-title":"Prog Neurobiol."},{"key":"10.1016\/j.fct.2010.10.011_b0170","doi-asserted-by":"crossref","first-page":"85","DOI":"10.3109\/10915818909009095","article-title":"Screening approaches to neurotoxicity: a functional observational battery","volume":"8","author":"Moser","year":"1989","journal-title":"J. Am. Coll. Toxicol."},{"key":"10.1016\/j.fct.2010.10.011_b0175","doi-asserted-by":"crossref","first-page":"1117","DOI":"10.1093\/jn\/101.9.1117","article-title":"Effects of excess levels of individual amino acids on growth of rats fed casein diets","volume":"101","author":"Muramatsu","year":"1971","journal-title":"J. Nutr."},{"key":"10.1016\/j.fct.2010.10.011_b0180","doi-asserted-by":"crossref","first-page":"216","DOI":"10.1016\/j.mce.2006.03.016","article-title":"Canavan disease and the role of N-acetyl-l-aspartate in myelin synthesis","volume":"252","author":"Namboodiri","year":"2006","journal-title":"Mol. Cell. Endocrinol."},{"key":"10.1016\/j.fct.2010.10.011_b0185","series-title":"Institute of Laboratory Animal Resources Commission on Life Sciences and the National Research Council. Guide for the Care and Use of Laboratory Animals","author":"NRC","year":"1996"},{"key":"10.1016\/j.fct.2010.10.011_b0190","doi-asserted-by":"crossref","first-page":"97","DOI":"10.3109\/10915818909009097","article-title":"Screening for neurotoxicity using a neurologically based examination and neuropathology","volume":"8","author":"O\u2019Donoghue","year":"1989","journal-title":"J. Am. Coll. Toxicol."},{"key":"10.1016\/j.fct.2010.10.011_b0195","unstructured":"OECD, 1998. Repeated dose 90-day oral toxicity study in rodents, No. 408 section 4 Health Effects. Organisation for Economic Co-operation and Development, last update September 21, 1998."},{"key":"10.1016\/j.fct.2010.10.011_b0200","unstructured":"OECD Principles of good laboratory practices, [C(97)186\/Final] (1998); Environmental Health and Safety Division. OECD Environment Directorate."},{"key":"10.1016\/j.fct.2010.10.011_b0205","doi-asserted-by":"crossref","first-page":"539","DOI":"10.1042\/bj1840539","article-title":"Synthesis of N-acetyl-l-aspartate by rat brain mitochondria and its involvement in mitochondrial\/cytosolic carbon transport","volume":"184","author":"Patel","year":"1979","journal-title":"Biochem. J."},{"key":"10.1016\/j.fct.2010.10.011_b0210","doi-asserted-by":"crossref","first-page":"207","DOI":"10.1007\/BF01258952","article-title":"Glutamate-type hypothalamic-pituitary syndrome in mice treated with aspartate or cysteate in infancy","volume":"35","author":"Schainker","year":"1974","journal-title":"J. Neural Transm."},{"key":"10.1016\/j.fct.2010.10.011_b0215","doi-asserted-by":"crossref","first-page":"232","DOI":"10.1152\/ajplegacy.1962.203.2.232","article-title":"Salivary gland changes after isoproterenol-induced enlargement","volume":"203","author":"Schneyer","year":"1962","journal-title":"Am. J. Physiol."},{"key":"10.1016\/j.fct.2010.10.011_b0220","doi-asserted-by":"crossref","first-page":"425","DOI":"10.1111\/j.1471-4159.1977.tb10690.x","article-title":"In vivo labeling of acetyl aspartyl peptides in mouse brain from intracranially and intraperitoneally administered acetyl-l-[U-14C]aspartate","volume":"29","author":"Sinichkin","year":"1977","journal-title":"J. Neurochem."},{"key":"10.1016\/j.fct.2010.10.011_b0225","doi-asserted-by":"crossref","first-page":"215","DOI":"10.1080\/15287397609529428","article-title":"Absorption, utilization, and safety of aspartic acid","volume":"2","author":"Stegink","year":"1976","journal-title":"J. Toxicol. Environ. Health"},{"key":"10.1016\/j.fct.2010.10.011_b0230","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.2010.10.011_b0235","doi-asserted-by":"crossref","first-page":"257","DOI":"10.1016\/S0021-9258(18)65789-8","article-title":"N-acetyl-l-aspartic acid in brain","volume":"1","author":"Tallan","year":"1956","journal-title":"J. Biol. Chem."},{"key":"10.1016\/j.fct.2010.10.011_b0240","doi-asserted-by":"crossref","first-page":"1658","DOI":"10.1111\/j.1471-4159.1985.tb07240.x","article-title":"N-acetylation of l-aspartate in the nervous system: differential distribution of a specific enzyme","volume":"45","author":"Truckenmiller","year":"1985","journal-title":"J. Neurochem."},{"key":"10.1016\/j.fct.2010.10.011_b0245","doi-asserted-by":"crossref","first-page":"531","DOI":"10.1016\/0301-0082(95)00014-M","article-title":"N-acetylaspartate in neuropsychiatric disorders","volume":"46","author":"Tsai","year":"1995","journal-title":"Prog. Neurobiol."},{"key":"10.1016\/j.fct.2010.10.011_b0250","unstructured":"U.S. EPA, 1989. Federal Insecticide, Fungicide and Rodenticide Act\/Toxic Substances Control Act (FIFRA\/TSCA); Good Laboratory Practice Standards; Final Rule. 40 CFR Part 160\/Part 792."},{"key":"10.1016\/j.fct.2010.10.011_b0255","doi-asserted-by":"crossref","first-page":"425","DOI":"10.1152\/ajplegacy.1962.202.3.425","article-title":"Submandibular salivary gland weight increase by administration of isoproterenol to rats","volume":"202","author":"Wells","year":"1962","journal-title":"Am. J. Physiol."},{"key":"10.1016\/j.fct.2010.10.011_b0260","doi-asserted-by":"crossref","first-page":"1293","DOI":"10.1152\/ajplegacy.1967.212.6.1293","article-title":"Salivary gland enlargement after administration of theophylline","volume":"212","author":"Wells","year":"1967","journal-title":"Am. J. Physiol."},{"key":"10.1016\/j.fct.2010.10.011_b0265","doi-asserted-by":"crossref","first-page":"313","DOI":"10.1152\/ajplegacy.1964.207.2.313","article-title":"Synergistic autonomic nervous regulation of accelerated salivary gland growth in rats","volume":"207","author":"Wells","year":"1964","journal-title":"Am. J. Physiol."},{"key":"10.1016\/j.fct.2010.10.011_b0270","doi-asserted-by":"crossref","first-page":"247","DOI":"10.1152\/ajplegacy.1967.212.2.247","article-title":"Functional hypertrophy and atrophy of the salivary glands of rats","volume":"212","author":"Wells","year":"1967","journal-title":"Am. J. Physiol."},{"key":"10.1016\/j.fct.2010.10.011_b0275","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.2010.10.011_b0280","doi-asserted-by":"crossref","first-page":"877","DOI":"10.1152\/ajplegacy.1965.208.5.877","article-title":"Taste receptors and sialadenotrophic action of proteolytic enzymes in rats","volume":"208","author":"Wells","year":"1965","journal-title":"Am. J. Physiol."},{"key":"10.1016\/j.fct.2010.10.011_b0285","doi-asserted-by":"crossref","first-page":"557","DOI":"10.1023\/A:1022091223498","article-title":"Identification and characterization of novel mutations of the aspartoacylase gene in non-Jewish patients with Canavan disease","volume":"25","author":"Zeng","year":"2002","journal-title":"J. Inher. Metabol. Dis."}],"container-title":["Food and Chemical Toxicology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S027869151000623X?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S027869151000623X?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2025,10,3]],"date-time":"2025-10-03T20:55:39Z","timestamp":1759524939000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S027869151000623X"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2011,1]]},"references-count":58,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2011,1]]}},"alternative-id":["S027869151000623X"],"URL":"https:\/\/doi.org\/10.1016\/j.fct.2010.10.011","relation":{},"ISSN":["0278-6915"],"issn-type":[{"value":"0278-6915","type":"print"}],"subject":[],"published":{"date-parts":[[2011,1]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Subchronic oral toxicity assessment of N-acetyl-l-aspartic acid in rats","name":"articletitle","label":"Article Title"},{"value":"Food and Chemical Toxicology","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.fct.2010.10.011","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"Copyright \u00a9 2010 Elsevier Ltd. All rights reserved.","name":"copyright","label":"Copyright"}]}}