{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,7]],"date-time":"2026-05-07T15:06:30Z","timestamp":1778166390616,"version":"3.51.4"},"reference-count":65,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2021,12,2]],"date-time":"2021-12-02T00:00:00Z","timestamp":1638403200000},"content-version":"am","delay-in-days":365,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#am"},{"start":{"date-parts":[[2020,12,2]],"date-time":"2020-12-02T00:00:00Z","timestamp":1606867200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000001","name":"National Science Foundation","doi-asserted-by":"publisher","award":["ECCS\u20101542174"],"award-info":[{"award-number":["ECCS\u20101542174"]}],"id":[{"id":"10.13039\/100000001","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["analyticalsciencejournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J of Applied Toxicology"],"published-print":{"date-parts":[[2021,8]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Little is known about the uptake, biodistribution, and biological responses of nanoparticles (NPs) and their toxicity in developing animals. Here, male and female juvenile Sprague\u2013Dawley rats received four consecutive daily doses of 10\u00a0mg\/kg Al<jats:sub>2<\/jats:sub>O<jats:sub>3<\/jats:sub> NP (diameter: 24\u00a0nm [transmission electron microscope], hydrodynamic diameter: 148\u00a0nm) or vehicle control (water) by gavage between postnatal days (PNDs) 17\u201320. Basic neurobehavioral and cardiac assessments were performed on PND 20. Animals were sacrificed on PND 21, and selected tissues were collected, weighed, and processed for histopathology or neurotransmitter analysis. The biodistribution of Al<jats:sub>2<\/jats:sub>O<jats:sub>3<\/jats:sub> NP in tissue sections of the intestine, liver, spleen, kidney, and lymph nodes were evaluated using enhanced dark\u2010field microscopy (EDM) and hyperspectral imaging (HSI). Liver\u2010to\u2010body weight ratio was significantly increased for male pups administered Al<jats:sub>2<\/jats:sub>O<jats:sub>3<\/jats:sub> NP compared with control. HSI suggested that Al<jats:sub>2<\/jats:sub>O<jats:sub>3<\/jats:sub> NP was more abundant in the duodenum and ileum tissue of the female pups compared with the male pups, whereas the abundance of NP was similar for males and females in the other tissues. The abundance of NP was higher in the liver compared with spleen, lymph nodes, and kidney. Homovanillic acid and norepinephrine concentrations in brain were significantly decreased following Al<jats:sub>2<\/jats:sub>O<jats:sub>3<\/jats:sub> NP administration in female and male pups, whereas 5\u2010hydroxyindoleacetic acid was significantly increased in male pups. EDM\/HSI indicates intestinal uptake of Al<jats:sub>2<\/jats:sub>O<jats:sub>3<\/jats:sub> NP following oral administration. Al<jats:sub>2<\/jats:sub>O<jats:sub>3<\/jats:sub> NP altered neurotransmitter\/metabolite concentrations in juvenile rats' brain tissues. Together, these data suggest that orally administered Al<jats:sub>2<\/jats:sub>O<jats:sub>3<\/jats:sub> NP interferes with the brain biochemistry in both female and male pups.<\/jats:p>","DOI":"10.1002\/jat.4122","type":"journal-article","created":{"date-parts":[[2020,12,2]],"date-time":"2020-12-02T22:17:20Z","timestamp":1606947440000},"page":"1316-1329","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Biodistribution, cardiac and neurobehavioral assessments, and neurotransmitter quantification in juvenile rats following oral administration of aluminum oxide nanoparticles"],"prefix":"10.1002","volume":"41","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7980-8958","authenticated-orcid":false,"given":"Ninell P.","family":"Mortensen","sequence":"first","affiliation":[{"name":"Discovery Sciences RTI International  Research Triangle Park North Carolina USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maria","family":"Moreno Caffaro","sequence":"additional","affiliation":[{"name":"Discovery Sciences RTI International  Research Triangle Park North Carolina USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Purvi R.","family":"Patel","sequence":"additional","affiliation":[{"name":"Discovery Sciences RTI International  Research Triangle Park North Carolina USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rodney W.","family":"Snyder","sequence":"additional","affiliation":[{"name":"Discovery Sciences RTI International  Research Triangle Park North Carolina USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Scott L.","family":"Watson","sequence":"additional","affiliation":[{"name":"Discovery Sciences RTI International  Research Triangle Park North Carolina USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shyam","family":"Aravamudhan","sequence":"additional","affiliation":[{"name":"Joint School of Nanoscience and Nanoengineering North Carolina A&amp;T State University  Greensboro North Carolina USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stephanie A.","family":"Montgomery","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine University of North Carolina at Chapel Hill  Chapel Hill North Carolina USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Timothy","family":"Lefever","sequence":"additional","affiliation":[{"name":"Discovery Sciences RTI International  Research Triangle Park North Carolina USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Susan J.","family":"Sumner","sequence":"additional","affiliation":[{"name":"UNC Nutrition Research Institute University of North Carolina at Chapel Hill  Kannapolis North Carolina USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Timothy R.","family":"Fennell","sequence":"additional","affiliation":[{"name":"Discovery Sciences RTI International  Research Triangle Park North Carolina USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2020,12,2]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12640-011-9264-9"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.3109\/17435390.2013.879342"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.3109\/17435390.2015.1107143"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1080\/01926230490465874"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1093\/mutage\/gep003"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.impact.2017.11.007"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.3791\/54161"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.3906\/zoo-1512-23"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.etap.2019.04.002"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1093\/toxsci\/59.2.260"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jsamd.2017.09.001"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.physiol.70.113006.100506"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.impact.2017.12.002"},{"issue":"4","key":"e_1_2_7_15_1","doi-asserted-by":"crossref","first-page":"iv15","DOI":"10.1136\/gut.47.suppl_4.iv15","article-title":"Anatomy and physiology of the enteric nervous system","volume":"47","author":"Costa M.","year":"2000","journal-title":"Gut"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrn3346"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1177\/1091581810397774"},{"key":"e_1_2_7_18_1","doi-asserted-by":"crossref","first-page":"787","DOI":"10.3748\/wjg.v16.i7.862","article-title":"Ontogeny, growth and development of the small intestine: Understanding pediatric gastroenterology","volume":"16","author":"Drozdowski L. A.","year":"2010","journal-title":"World Journal of Gastroenterology"},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.1002\/jat.3387"},{"key":"e_1_2_7_20_1","unstructured":"FutureMarkets.2013.The global market for aluminium oxide nanoparticles. Future Markets I (ed)."},{"key":"e_1_2_7_21_1","doi-asserted-by":"publisher","DOI":"10.1002\/jbio.201600125"},{"key":"e_1_2_7_22_1","doi-asserted-by":"publisher","DOI":"10.1002\/j.1536-4801.1989.tb09825.x"},{"key":"e_1_2_7_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biomaterials.2010.07.011"},{"key":"e_1_2_7_24_1","doi-asserted-by":"publisher","DOI":"10.3109\/17435390.2014.996192"},{"key":"e_1_2_7_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.yrtph.2015.11.018"},{"key":"e_1_2_7_26_1","doi-asserted-by":"publisher","DOI":"10.3390\/nano10020305"},{"key":"e_1_2_7_27_1","doi-asserted-by":"publisher","DOI":"10.1080\/08958370701874663"},{"key":"e_1_2_7_28_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-020-59710-z"},{"key":"e_1_2_7_29_1","doi-asserted-by":"publisher","DOI":"10.1093\/mutage\/geu038"},{"key":"e_1_2_7_30_1","doi-asserted-by":"publisher","DOI":"10.1093\/jn\/103.5.744"},{"key":"e_1_2_7_31_1","doi-asserted-by":"publisher","DOI":"10.1186\/1743-8977-10-36"},{"key":"e_1_2_7_32_1","doi-asserted-by":"publisher","DOI":"10.3389\/fnins.2012.00026"},{"key":"e_1_2_7_33_1","doi-asserted-by":"publisher","DOI":"10.1186\/1743-8977-8-18"},{"key":"e_1_2_7_34_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrn3071"},{"key":"e_1_2_7_35_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-med-012309-103958"},{"key":"e_1_2_7_36_1","doi-asserted-by":"publisher","DOI":"10.1080\/01926230701595292"},{"key":"e_1_2_7_37_1","doi-asserted-by":"publisher","DOI":"10.1002\/da.22084"},{"key":"e_1_2_7_38_1","doi-asserted-by":"publisher","DOI":"10.1002\/jat.1058"},{"key":"e_1_2_7_39_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1114397"},{"key":"e_1_2_7_40_1","doi-asserted-by":"publisher","DOI":"10.1021\/ar300022h"},{"key":"e_1_2_7_41_1","volume-title":"Guide for the care and use of laboratory animals","author":"NRC","year":"2011"},{"key":"e_1_2_7_42_1","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.2000.80.4.1633"},{"key":"e_1_2_7_43_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00284-014-0763-9"},{"key":"e_1_2_7_44_1","doi-asserted-by":"publisher","DOI":"10.1002\/jat.3233"},{"key":"e_1_2_7_45_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00204-014-1256-0"},{"key":"e_1_2_7_46_1","doi-asserted-by":"publisher","DOI":"10.1293\/tox.26.29"},{"key":"e_1_2_7_47_1","doi-asserted-by":"publisher","DOI":"10.1016\/B978-0-12-802682-3.00005-7"},{"key":"e_1_2_7_48_1","unstructured":"Project on Emerging Nanotechnologies. (2019).Consumer Products Inventory: An inventory of nanotechnology\u2010based consumer products introduced on the market. Woodrow Wilson International Center for Scholars. (http:\/\/www.nanotechproject.org\/cpi\/). Website accessed November 18th 2019."},{"key":"e_1_2_7_49_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.reprotox.2015.07.072"},{"key":"e_1_2_7_50_1","doi-asserted-by":"publisher","DOI":"10.3389\/fnins.2014.00404"},{"key":"e_1_2_7_51_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1440-1681.1999.02987.x"},{"key":"e_1_2_7_52_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2012.00046"},{"key":"e_1_2_7_53_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1119339109"},{"key":"e_1_2_7_54_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pneurobio.2013.04.001"},{"key":"e_1_2_7_55_1","doi-asserted-by":"publisher","DOI":"10.3109\/01480545.2013.866134"},{"key":"e_1_2_7_56_1","doi-asserted-by":"publisher","DOI":"10.1093\/jn\/138.5.954"},{"key":"e_1_2_7_57_1","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.16352"},{"key":"e_1_2_7_58_1","doi-asserted-by":"publisher","DOI":"10.1203\/00006450-199207000-00010"},{"key":"e_1_2_7_59_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00204-019-02599-z"},{"key":"e_1_2_7_60_1","doi-asserted-by":"publisher","DOI":"10.1159\/000241597"},{"key":"e_1_2_7_61_1","first-page":"83","article-title":"Decrease in intestinal permeability to polyethylene glycol 1000 during development in the pig","volume":"11","author":"Westrom B. R.","year":"1989","journal-title":"Journal of Developmental Physiology"},{"key":"e_1_2_7_62_1","doi-asserted-by":"publisher","DOI":"10.3109\/10408444.2014.934439"},{"key":"e_1_2_7_63_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF00584862"},{"key":"e_1_2_7_64_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.toxlet.2015.06.007"},{"key":"e_1_2_7_65_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI109126"},{"key":"e_1_2_7_66_1","first-page":"6243","article-title":"Effects of silver nanoparticles on neonatal testis development in mice","volume":"10","author":"Zhang X. F.","year":"2015","journal-title":"International Journal of Nanomedicine"}],"container-title":["Journal of Applied Toxicology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jat.4122","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/jat.4122","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/analyticalsciencejournals.onlinelibrary.wiley.com\/doi\/am-pdf\/10.1002\/jat.4122","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/analyticalsciencejournals.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jat.4122","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,15]],"date-time":"2025-10-15T09:58:32Z","timestamp":1760522312000},"score":1,"resource":{"primary":{"URL":"https:\/\/analyticalsciencejournals.onlinelibrary.wiley.com\/doi\/10.1002\/jat.4122"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,12,2]]},"references-count":65,"journal-issue":{"issue":"8","published-print":{"date-parts":[[2021,8]]}},"alternative-id":["10.1002\/jat.4122"],"URL":"https:\/\/doi.org\/10.1002\/jat.4122","archive":["Portico"],"relation":{},"ISSN":["0260-437X","1099-1263"],"issn-type":[{"value":"0260-437X","type":"print"},{"value":"1099-1263","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,12,2]]},"assertion":[{"value":"2020-04-14","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2020-11-13","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2020-12-02","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}