{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,10]],"date-time":"2026-03-10T13:45:13Z","timestamp":1773150313090,"version":"3.50.1"},"reference-count":20,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2009,3,20]],"date-time":"2009-03-20T00:00:00Z","timestamp":1237507200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Birth Defects Research Pt B"],"published-print":{"date-parts":[[2009,4]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p><jats:bold>BACKGROUND:<\/jats:bold> In order to justify clinical studies in women of child\u2010bearing age with artemisone, a new artimisinin derivative, studies to assess fertility and early embryonic development in rats, developmental toxicity in rats and rabbits, and peri\u2010post natal development in rats were performed. <jats:bold>METHODS AND RESULTS:<\/jats:bold> In the study on fertility and early embryonic development (dose levels 0\u20105\u201020\u201080 mg\/kg bw\/day), doses inducing clinical and organ toxicity were used. Only in severe toxicity conditions, a reduction of the number of estruses, a prolonged time to insemination, decreased numbers of corpora lutea, implantation sites, and viable fetuses were found. Two developmental toxicity studies were performed in rats (dose levels 0\u20101\u20102 mg\/kg bw\/day) and rabbits (dose levels 0\u20102.5\u20105.0\u20107.5 mg\/kg bw\/day). It was shown that rats were about 5 times more sensitive than rabbits. In rats, artemisone induced total litter loss (late resorptions) at 2 mg\/kg body weight and above with an increased incidence of a common vascular variation and retarded ossification at this dose. In rabbits, maternal toxicity, abortion and a slightly increased incidence of cardiac ventricular septal defects was observed at 7.5 mg\/kg body weight. In a pre\u2010 and postnatal developmental toxicity study in rats (dose levels 0\u20101\u20102\u20104 mg\/kg bw\/day), 4 mg\/kg body weight artemisone induced clinical symptoms and affected postnatal survival, body weight gain in the F1 pups, and motor activity. <jats:bold>CONCLUSIONS:<\/jats:bold> In summary, artemisone was shown to be embryo\u2010 and fetotoxic and induced cardiac ventricular septal defects and retarded ossification in dosages where total litter loss and abortions were observed. However, no effect on reproductive and developmental parameters below severe toxic dosages could be observed. <jats:italic>Birth Defects Res (Part B)<\/jats:italic>86: 131\u2010143, 2009. \u00a9 2009 Wiley\u2010Liss, Inc.<\/jats:p>","DOI":"10.1002\/bdrb.20192","type":"journal-article","created":{"date-parts":[[2009,3,20]],"date-time":"2009-03-20T18:06:24Z","timestamp":1237572384000},"page":"131-143","source":"Crossref","is-referenced-by-count":18,"title":["Developmental and reproductive toxicity studies on artemisone"],"prefix":"10.1002","volume":"86","author":[{"given":"G.","family":"Schmuck","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"A.\u2010M.","family":"Klaus","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"F.","family":"Kr\u00f6tlinger","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"F.W.","family":"Langewische","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2009,3,20]]},"reference":[{"key":"e_1_2_5_2_1","first-page":"31","article-title":"Studies on the toxicity of qinghaosu and its derivative","volume":"2","author":"China Cooperative Research Group","year":"1982","journal-title":"J Trad Chin Med"},{"key":"e_1_2_5_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/bdrb.20027"},{"key":"e_1_2_5_4_1","doi-asserted-by":"publisher","DOI":"10.1002\/bdrb.20165"},{"key":"e_1_2_5_5_1","doi-asserted-by":"publisher","DOI":"10.1002\/bdrb.20163"},{"key":"e_1_2_5_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.micinf.2004.09.002"},{"key":"e_1_2_5_7_1","doi-asserted-by":"publisher","DOI":"10.1002\/anie.200503071"},{"key":"e_1_2_5_8_1","unstructured":"ICH guideline.2006.Detection of Toxicity to Reproduction for Medicinal Products. 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Artemisinin derivatives I. Classic examples in toxicologic pathology XIII; Seminar of the ESTP and the PhD program at the university of veterinary medicine in Hannover (24\u201325 Feb. 2006)http:\/\/212.227.190.64\/estp\/dra2007ebe\/schmuck2006\/text.htm."},{"key":"e_1_2_5_19_1","doi-asserted-by":"publisher","DOI":"10.1002\/bdrb.20157"},{"key":"e_1_2_5_20_1","doi-asserted-by":"publisher","DOI":"10.1002\/bdrb.20092"},{"key":"e_1_2_5_21_1","unstructured":"World Health Organization.2003. Assessment of the safety of artemisinin compounds in pregnancy. WHO\/CDS\/MAL\/2003.1094; WHO\/RBM\/TDR\/Artemisinin\/03.1 (www.who.int\/tdr\/publications\/publications\/artemisinin\u2010pregn.htm)."}],"container-title":["Birth Defects Research Part B: Developmental and Reproductive Toxicology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fbdrb.20192","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/bdrb.20192","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,17]],"date-time":"2023-10-17T02:38:23Z","timestamp":1697510303000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/bdrb.20192"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2009,3,20]]},"references-count":20,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2009,4]]}},"alternative-id":["10.1002\/bdrb.20192"],"URL":"https:\/\/doi.org\/10.1002\/bdrb.20192","archive":["Portico"],"relation":{},"ISSN":["1542-9733","1542-9741"],"issn-type":[{"value":"1542-9733","type":"print"},{"value":"1542-9741","type":"electronic"}],"subject":[],"published":{"date-parts":[[2009,3,20]]}}}