{"@context":{"@vocab":"https://cir.nii.ac.jp/schema/1.0/","rdfs":"http://www.w3.org/2000/01/rdf-schema#","dc":"http://purl.org/dc/elements/1.1/","dcterms":"http://purl.org/dc/terms/","foaf":"http://xmlns.com/foaf/0.1/","prism":"http://prismstandard.org/namespaces/basic/2.0/","cinii":"http://ci.nii.ac.jp/ns/1.0/","datacite":"https://schema.datacite.org/meta/kernel-4/","ndl":"http://ndl.go.jp/dcndl/terms/","jpcoar":"https://github.com/JPCOAR/schema/blob/master/2.0/"},"@id":"https://cir.nii.ac.jp/crid/1390282679879459456.json","@type":"Article","productIdentifier":[{"identifier":{"@type":"DOI","@value":"10.2131/jts.8.supplementi_1"}},{"identifier":{"@type":"URI","@value":"http://www.jstage.jst.go.jp/article/jts1976/8/SupplementI/8_SupplementI_1/_pdf"}},{"identifier":{"@type":"NAID","@value":"110001804214"}},{"identifier":{"@type":"URI","@value":"https://search.jamas.or.jp/link/ui/1984070835"}}],"dc:title":[{"@language":"en","@value":"ACUTE TOXICITY OF RANITIDINE AND ITS METABOLITE IN MICE, RATS AND RABBITS, AND SUBACUTE ORAL TOXICITY OF RANITIDINE IN RATS"},{"@language":"ja","@value":"Ranitidine hydrochlorideのマウス, ラットおよびウサギにおける急性毒性並びにラットにおける経口投与亜急性毒性試験"}],"dc:language":"en","description":[{"type":"abstract","notation":[{"@language":"en","@value":"Acute and subacute toxicities of ranitidine hydrochloride, a new histamine H<SUB>2</SUB>-receptor antagonist, and acute toxicity of ranitidine N-oxide, a metabolite of ranitidine hydrochloride, were investigated. The results are summarized as follows : (1) Oral, intravenous; subcutaneous, intraperitoneal and intramuscular LD<SUB>50</SUB> values of ranitidine hydrochloride in 5- and 12-weeks old mice and rats and 12-weeks old rabbits were ranged from ca. 60mg/kg (12-weeks old male mice, i.v.) to 6610mg/kg (12-webks old male rats; p.o.). In comparison of the LD<SUB>50</SUB> values, it was revealed that female rats were more sensitive to the drug than males in the case of oral administration. (2) A single intravenous injection with ranitidine N-oxide at a dose of 1000 mg/kg, induced no lethal cases in mice, indicating that the N-oxide has very low toxicity in a comparison with that of ranitidine hydrochloride. (3) In the subacute toxicity test, male and female rats were orally administered with ranitidine hydrochloride for 35 days. Dose dependent changes such as increase in liver weight and water consumption, decrease in spontaneous movement and others were induced at doses of more than 500 mg/kg/day in females and 1000 mg/kg/day in males. These results indicate that the no effects were observed at levels of 250 mg/kg/day in females and 500 mg/kg/day in males. In the recovery test, however, no marked changes were observed in the rats which had been administered at 1000 and 2000 mg/kg/day for 35 days."},{"@value":"Histamine H<SUB>2</SUB>-receptor antagonistであり, 消化性潰瘍の治療剤として期待される ranitidine hydrochlorideおよびその代謝産物の一種であるranitidine N-oxideの急性毒性並びに35日間経口投与によるranitidine hydrochlorideの亜急性毒性を検討し, 次のような成績を得た。(1) 雌雄の5週齢および12週齢マウスおよびラット並びに12週齢ウサギに対するranitidine hydrochlorideの経口, 静脈内, 皮下, 腹腔内および筋肉内投与によるLD<SUB>50</SUB>値は約60mg/kg(12週齢雄マウス, 静脈内) ～6610 m9/k9 (12週齢雄ラット, 経口)の範囲内であった。マウスにおいてはウサギおよびラットの場合よりも低いLD<SUB>50</SUB>値がみられ, ラットの経口投与の場合にのみ雌におけるLD<SUB>50</SUB>値は雄よりも有意に低かった。(2) 急性毒性試験における症状としては, 使用したすべての動物種に共通して不規則な呼吸・眼球突出・チアノーゼ・流涎・ジャンピング・疾走・強直性ないし間代性の痙撃が主なものであった。しかしこれらの症状は24時間以内には消失し, それ以降は ranitidine hydrochloride溶液の高張性に起因すると思われる投与部位(皮下または筋肉内投与)の壊死等の局所障害性以外には著変はみられなかった。(3) RanitidinehydrochlorideのLD<SUB>50</SUB>値の約12倍である1000mg/kgのranitidine N-oxide をマウスの静脈内に投与したが,死亡例は認められなかったことからranitidine N-oxideの毒性はほとんど無視できるものと考えられた。(4) Ranitidine hydrochlorideの0.25・0.5・1.0・2.0および2.5g/kg/dayのラットにおける35日間連続経口投与亜急性毒性試験においては, 1.0または2.0 g/kg/day以上の投与群の雌雄に自発運動の抑制, 流涎によると思われる被毛の着色, 水消費量の増加, 血小板数および肝重量の増加, 肝臓の滑面小胞体の軽度な増加等が認められた。しかしこれらの変化は31日間の回復期間後にはほほ消失した。(5) 死亡例は2.5 g/kg/day群のみにみられ, これらにおける死亡前の症状はいずれも急性毒性試験における症状と類似していた。(6) Ranitidine hydrochlorideの35日間経口投与における最大無作用量は雄で0.5, 雌で0.25 g/kg/dayであった。"}],"abstractLicenseFlag":"disallow"}],"creator":[{"@id":"https://cir.nii.ac.jp/crid/1410572171405622661","@type":"Researcher","personIdentifier":[{"@type":"NRID","@value":"9000020773347"}],"foaf:name":[{"@language":"en","@value":"TAMURA Joh"},{"@language":"ja","@value":"田村 穣"}]},{"@id":"https://cir.nii.ac.jp/crid/1420564276161797888","@type":"Researcher","personIdentifier":[{"@type":"KAKEN_RESEARCHERS","@value":"30409205"},{"@type":"NRID","@value":"1000030409205"},{"@type":"NRID","@value":"9000020775214"},{"@type":"NRID","@value":"9000003836236"},{"@type":"NRID","@value":"9000021358630"},{"@type":"NRID","@value":"9000253193618"},{"@type":"NRID","@value":"9000254552201"},{"@type":"NRID","@value":"9000256283333"},{"@type":"NRID","@value":"9000415201033"},{"@type":"NRID","@value":"9000020766507"},{"@type":"NRID","@value":"9000003373891"},{"@type":"NRID","@value":"9000004782345"},{"@type":"NRID","@value":"9000020519422"},{"@type":"NRID","@value":"9000005708965"},{"@type":"NRID","@value":"9000003094756"},{"@type":"NRID","@value":"9000004857435"},{"@type":"NRID","@value":"9000345259940"},{"@type":"NRID","@value":"9000401705992"},{"@type":"NRID","@value":"9000401705931"},{"@type":"NRID","@value":"9000258011945"},{"@type":"NRID","@value":"9000255742349"},{"@type":"NRID","@value":"9000018990246"},{"@type":"NRID","@value":"9000004478049"},{"@type":"NRID","@value":"9000256166969"},{"@type":"NRID","@value":"9000261658835"},{"@type":"NRID","@value":"9000018501964"},{"@type":"NRID","@value":"9000004758009"},{"@type":"NRID","@value":"9000004860660"},{"@type":"NRID","@value":"9000255824559"},{"@type":"NRID","@value":"9000257986037"},{"@type":"NRID","@value":"9000020773352"},{"@type":"NRID","@value":"9000390884321"},{"@type":"NRID","@value":"9000318140918"},{"@type":"NRID","@value":"9000253508047"},{"@type":"NRID","@value":"9000398139914"},{"@type":"NRID","@value":"9000257864042"},{"@type":"NRID","@value":"9000020777964"},{"@type":"NRID","@value":"9000004857437"},{"@type":"NRID","@value":"9000401837898"},{"@type":"NRID","@value":"9000283114802"},{"@type":"NRID","@value":"9000021037777"},{"@type":"NRID","@value":"9000283354707"},{"@type":"NRID","@value":"9000004334294"},{"@type":"NRID","@value":"9000253112728"},{"@type":"NRID","@value":"9000392675708"},{"@type":"NRID","@value":"9000256285272"},{"@type":"NRID","@value":"9000020770327"},{"@type":"NRID","@value":"9000003865020"},{"@type":"NRID","@value":"9000006111196"},{"@type":"NRID","@value":"9000390884842"},{"@type":"NRID","@value":"9000258073354"},{"@type":"NRID","@value":"9000257863904"},{"@type":"NRID","@value":"9000002493823"},{"@type":"NRID","@value":"9000290137109"},{"@type":"NRID","@value":"9000253435096"},{"@type":"NRID","@value":"9000254270691"},{"@type":"NRID","@value":"9000255842241"},{"@type":"NRID","@value":"9000283130409"},{"@type":"NRID","@value":"9000401709799"},{"@type":"NRID","@value":"9000258160907"},{"@type":"NRID","@value":"9000257931183"},{"@type":"NRID","@value":"9000020773779"},{"@type":"NRID","@value":"9000003618838"},{"@type":"NRID","@value":"9000003642134"},{"@type":"NRID","@value":"9000004771351"},{"@type":"NRID","@value":"9000391625589"},{"@type":"NRID","@value":"9000256166729"},{"@type":"NRID","@value":"9000341542076"},{"@type":"NRID","@value":"9000281478735"},{"@type":"NRID","@value":"9000365530318"},{"@type":"NRID","@value":"9000283354964"},{"@type":"NRID","@value":"9000258161188"},{"@type":"NRID","@value":"9000364165296"},{"@type":"NRID","@value":"9000401690019"},{"@type":"RESEARCHMAP","@value":"https://researchmap.jp/7000009105"}],"foaf:name":[{"@language":"en","@value":"SATO Norio"},{"@language":"ja","@value":"佐藤 憲雄"}]},{"@id":"https://cir.nii.ac.jp/crid/1410282679879459456","@type":"Researcher","personIdentifier":[{"@type":"NRID","@value":"9000020773358"}],"foaf:name":[{"@language":"en","@value":"EZAKI Hiroshi"},{"@language":"ja","@value":"江崎 洋志"}]},{"@id":"https://cir.nii.ac.jp/crid/1410282679879459463","@type":"Researcher","personIdentifier":[{"@type":"NRID","@value":"9000020773365"}],"foaf:name":[{"@language":"en","@value":"MIYAMOTO Harumi"},{"@language":"ja","@value":"宮本 晴美"}]},{"@id":"https://cir.nii.ac.jp/crid/1410572171405622659","@type":"Researcher","personIdentifier":[{"@type":"NRID","@value":"9000020773369"}],"foaf:name":[{"@language":"en","@value":"ODA Sanae"},{"@language":"ja","@value":"小田 早苗"}]},{"@id":"https://cir.nii.ac.jp/crid/1410282679879459458","@type":"Researcher","personIdentifier":[{"@type":"NRID","@value":"9000020773375"}],"foaf:name":[{"@language":"en","@value":"HIRAI Kiyomi"},{"@language":"ja","@value":"平井 清美"}]},{"@id":"https://cir.nii.ac.jp/crid/1410572171405622660","@type":"Researcher","personIdentifier":[{"@type":"NRID","@value":"9000020773378"}],"foaf:name":[{"@language":"en","@value":"TOKADO Hiroshi"},{"@language":"ja","@value":"戸門 洋志"}]},{"@id":"https://cir.nii.ac.jp/crid/1410572171405622658","@type":"Researcher","personIdentifier":[{"@type":"NRID","@value":"9000020773384"}],"foaf:name":[{"@language":"en","@value":"MATSUMOTO Michio"},{"@language":"ja","@value":"松本 道男"}]},{"@id":"https://cir.nii.ac.jp/crid/1410572171405622657","@type":"Researcher","personIdentifier":[{"@type":"NRID","@value":"9000020773388"}],"foaf:name":[{"@language":"en","@value":"SHIRAI Toshikazu"},{"@language":"ja","@value":"白井 俊一"}]}],"publication":{"publicationIdentifier":[{"@type":"PISSN","@value":"03881350"},{"@type":"LISSN","@value":"03881350"},{"@type":"EISSN","@value":"18803989"},{"@type":"NCID","@value":"AN00002808"}],"prism:publicationName":[{"@language":"en","@value":"The Journal of Toxicological Sciences"},{"@language":"ja","@value":"Ｔｈｅ　Ｊｏｕｒｎａｌ　ｏｆ　Ｔｏｘｉｃｏｌｏｇｉｃａｌ　Ｓｃｉｅｎｃｅｓ"},{"@language":"en","@value":"J. Toxicol. Sci."}],"dc:publisher":[{"@language":"en","@value":"The Japanese Society of Toxicology"},{"@language":"ja","@value":"一般社団法人　日本毒性学会"}],"prism:publicationDate":"1983","prism:volume":"8","prism:number":"SupplementI","prism:startingPage":"1","prism:endingPage":"24"},"reviewed":"false","url":[{"@id":"http://www.jstage.jst.go.jp/article/jts1976/8/SupplementI/8_SupplementI_1/_pdf"},{"@id":"https://search.jamas.or.jp/link/ui/1984070835"}],"availableAt":"1983","foaf:topic":[{"@id":"https://cir.nii.ac.jp/all?q=Acute%20and%20subacute%20toxicities","dc:title":"Acute and subacute toxicities"}],"relatedProduct":[{"@id":"https://cir.nii.ac.jp/crid/1390282679876769024","@type":"Article","relationType":["isReferencedBy"],"jpcoar:relatedTitle":[{"@language":"en","@value":"Relation between statistics and treatment-related changes obtained from toxicity studies in rats: if detected a significant difference in low or middle dose for quantitative values, this change is considered as incidental change?"}]},{"@id":"https://cir.nii.ac.jp/crid/1570291224648886784","@type":"Article","relationType":["isCitedBy"],"jpcoar:relatedTitle":[{"@language":"ja","@value":"Lafutidine (FRG-8813)の生殖・発生毒性試験(第4報)ウサギを用いた経口投与による胎児の器官形成期投与試験"},{"@language":"en","@value":"Reproductive and Developmental Toxicity Studies of Lafutidine^<***> (FRG-8813)4. Teratogenicity of Study in Rabbits by Oral Administraion"}]},{"@id":"https://cir.nii.ac.jp/crid/1573105974416105984","@type":"Article","relationType":["isCitedBy"],"jpcoar:relatedTitle":[{"@language":"ja","@value":"Lafutidine (FRG-8813)の毒性試験(第2報)ラットを用いた経口投与による13週間反復投与毒性試験および6週間回復性試験"},{"@language":"en","@value":"Toxicological Studies of Lafutidine^<***> (FRG-8813)2.Thirteen-Week Repeated Dose Toxicity Study in Rats by Oral Administration, with a 6-Week Recovery Study"}]}],"dataSourceIdentifier":[{"@type":"JALC","@value":"oai:japanlinkcenter.org:0036254429"},{"@type":"CROSSREF","@value":"10.2131/jts.8.supplementi_1"},{"@type":"CIA","@value":"110001804214"},{"@type":"CROSSREF","@value":"10.2131/jts.35.79_references_DOI_6KHn5Wg16ZY6CAXlgK54dZa3teO"}]}