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Al ammonium sulfate is one of the Al compounds that is widely used as a food additive. However, the effects of the oral administration of Al ammonium sulfate on physical development and behavior remain to be examined.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>In this study, we investigated the effects of the administration of Al ammonium sulfate 12\u2010water dissolved in drinking water (0.075 mg\/mL) beginning in adolescence on various types of behavior in adult female C57<jats:styled-content style=\"fixed-case\">BL<\/jats:styled-content>\/6J mice through a battery of behavioral tests (low\u2010dose experiment; Experiment 1). We further examined the behavioral effects of the oral administration of a higher dose of the Al compound in drinking water (1 mg\/mL) beginning in the prenatal period on behavior in adult male and female mice (high\u2010dose experiment; Experiment 2).<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>In the low\u2010dose experiment, in which females\u2019 oral intake of Al was estimated to be 0.97 mg Al\/kg\/d as adults, Al\u2010treated females exhibited an increase in total arm entries in the elevated plus maze test, an initial decrease and subsequent increase in immobility in the forced swim test, and reduced freezing in the fear conditioning test approximately 1 month after the conditioning session compared with vehicle\u2010treated females (uncorrected <jats:italic>P<\/jats:italic> &lt; .05). However, the behavioral differences did not reach a statistically significant level after correction for multiple testing. In the high\u2010dose experiment, in which animals\u2019 oral intakes were estimated to be about ten times higher than those in the low\u2010dose experiment, behavioral differences found in the low\u2010dose experiment were not observed in high\u2010dose Al\u2010treated mice, suggesting that the results of the low\u2010dose experiment might be false positives. Additionally, although high\u2010dose Al\u2010treated females exhibited increased social contacts with unfamiliar conspecifics and impaired reference memory performance, and high\u2010dose Al\u2010treated mice exhibited decreases in prepulse inhibition and in correct responses in the working memory task (uncorrected <jats:italic>P<\/jats:italic> &lt; .05), the differences in any of the behavioral measures did not reach the significance level after correction for multiple testing.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Our results show that long\u2010term oral exposure to Al ammonium sulfate at the doses used in this study may have the potential to induce some behavioral changes in C57<jats:styled-content style=\"fixed-case\">BL<\/jats:styled-content>\/6J mice. However, the behavioral effects of Al were small and statistically weak, as indicated by the fact that the results failed to reach the study\u2010wide significance level. Thus, further study will be needed to replicate the results and reevaluate the behavioral outcomes of oral intake of Al ammonium sulfate.<\/jats:p><\/jats:sec>","DOI":"10.1002\/npr2.12002","type":"journal-article","created":{"date-parts":[[2018,1,2]],"date-time":"2018-01-02T09:20:40Z","timestamp":1514884840000},"page":"18-36","source":"Crossref","is-referenced-by-count":9,"title":["Behavioral effects of long\u2010term oral administration of aluminum ammonium sulfate in male and female C57<scp>BL<\/scp>\/6J mice"],"prefix":"10.1002","volume":"38","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4843-6949","authenticated-orcid":false,"given":"Hirotaka","family":"Shoji","sequence":"first","affiliation":[{"name":"Division of Systems Medical Science Institute for Comprehensive Medical Science Fujita Health University Toyoake Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yasuhiro","family":"Irino","sequence":"additional","affiliation":[{"name":"Division of Evidence\u2010Based Laboratory Medicine Kobe University Graduate School of Medicine Kobe Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Masaru","family":"Yoshida","sequence":"additional","affiliation":[{"name":"Division of Metabolomics Research Department of Internal Related Kobe University Graduate School of Medicine Kobe Japan"},{"name":"Division of Gastroenterology Department of Internal Medicine Kobe University Graduate School of Medicine Kobe Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0137-8200","authenticated-orcid":false,"given":"Tsuyoshi","family":"Miyakawa","sequence":"additional","affiliation":[{"name":"Division of Systems Medical Science Institute for Comprehensive Medical Science Fujita Health University Toyoake Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2018,2,9]]},"reference":[{"key":"e_1_2_10_2_1","unstructured":"Joint FAO\/WHO Expert Committee on Food Additives.Evaluation of certain food additives and contaminants: seventy\u2010fourth report. 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