{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T05:31:45Z","timestamp":1790659905552,"version":"4.1.0"},"reference-count":60,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2019,1,15]],"date-time":"2019-01-15T00:00:00Z","timestamp":1547510400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81703257"],"award-info":[{"award-number":["81703257"]}],"id":[{"id":"10.13039\/501100001809","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":[[2019,5]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Existing literature pointed out that the liver may be the target organ of toxicity induced by titanium dioxide nanoparticles (TiO\n                    <jats:sub>2<\/jats:sub>\n                    NPs) via oral exposure. Gender differences in health effects widely exist and relevant toxicological research is important for safety assessment. To explore the gender susceptibility of TiO\n                    <jats:sub>2<\/jats:sub>\n                    NP\u2010induced hepatic toxicity and the underlying mechanism, we examined female and male Sprague\u2010Dawley rats administrated with TiO\n                    <jats:sub>2<\/jats:sub>\n                    NPs orally at doses of 0, 2, 10 and 50\u00a0mg\/kg body weight per day for 90\u00a0days. The serum biochemical indicators and liver pathological observation were used to assess hepatic toxicity. We found significant hepatic toxicity could be induced by subchronic oral exposure to TiO\n                    <jats:sub>2<\/jats:sub>\n                    NPs, which was more obvious and severe in female rats. No accumulation of TiO\n                    <jats:sub>2<\/jats:sub>\n                    NPs in the liver was observed, indicating that hepatic toxicity may not be caused through direct pathways. Oxidized glutathione, lipid peroxidation products increased significantly and reduced glutathione decreased significantly in the liver of rats in repeated TiO\n                    <jats:sub>2<\/jats:sub>\n                    NP\u2010exposed groups. Hematological parameters of white blood cells and inflammatory cytokines in serum including interleukin 1\u03b1, interleukin 4 and tumor necrosis factor also increased significantly. Indirect pathways through initiating oxidative stress and inflammatory responses were suggested as the possible mechanism of the hepatic toxicity in this experiment. The higher sensitivity to redox homeostasis imbalance and inflammation of female rats may be the main reason for gender differences. Our research suggested that gender should be a susceptible factor for identifying and monitoring long\u2010term oral toxicity of TiO\n                    <jats:sub>2<\/jats:sub>\n                    NPs.\n                  <\/jats:p>","DOI":"10.1002\/jat.3769","type":"journal-article","created":{"date-parts":[[2019,1,15]],"date-time":"2019-01-15T04:23:08Z","timestamp":1547526188000},"page":"807-819","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":52,"title":["Gender difference in hepatic toxicity of titanium dioxide nanoparticles after subchronic oral exposure in Sprague\u2010Dawley rats"],"prefix":"10.1002","volume":"39","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3370-5184","authenticated-orcid":false,"given":"Zhangjian","family":"Chen","sequence":"first","affiliation":[{"name":"Department of Occupational and Environmental Health Sciences, School of Public Health Peking University  Beijing 100191 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Di","family":"Zhou","sequence":"additional","affiliation":[{"name":"Department of Occupational and Environmental Health Sciences, School of Public Health Peking University  Beijing 100191 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shupei","family":"Zhou","sequence":"additional","affiliation":[{"name":"Department of Laboratory Animal Science, Health Science Center Peking University  Beijing 100191 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3981-7221","authenticated-orcid":false,"given":"Guang","family":"Jia","sequence":"additional","affiliation":[{"name":"Department of Occupational and Environmental Health Sciences, School of Public Health Peking University  Beijing 100191 China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2019,1,15]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.96.26.15161"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1097\/ACI.0b013e32835a6dd6"},{"key":"e_1_2_8_4_1","first-page":"215","article-title":"Gender differences in pulmonary disease","volume":"70","author":"Caracta C. 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