{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,19]],"date-time":"2026-01-19T23:51:39Z","timestamp":1768866699593,"version":"3.49.0"},"reference-count":42,"publisher":"Wiley","issue":"4-5","license":[{"start":{"date-parts":[[2016,8,12]],"date-time":"2016-08-12T00:00:00Z","timestamp":1470960000000},"content-version":"vor","delay-in-days":11,"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":[[2016,8]]},"abstract":"<jats:p>A humanized monoclonal antibody targeting transforming growth factor \u03b21 (TGF\u2010\u03b21 mab) has been used in development for the treatment of chronic kidney disease. Embryo\u2010fetal development studies were conducted in rats and rabbits using 30 and 25 animals per group, respectively. The TGF\u2010\u03b21 mab was administered subcutaneously to rats at 0, 2, or 50 mg\/kg\/dose on gestation days (GDs) 6, 10, and 14 and intravenously to rabbits at 0 or 3 mg\/kg\/dose on GDs 7, 12 to 19, and at 30 mg\/kg\/dose on GDs 7, 12, 14, 16, and 18. Maternal reproductive endpoints and fetal viability, weight, and morphology were evaluated. There was no indication of maternal or embryo\u2010fetal toxicity in the rat. Effects in the rabbit were limited to the fetus where the 30 mg\/kg TGF\u2010\u03b21 mab dose produced a slight decrease in fetal weight and an increase in the incidence of retrocaval ureter and an absent and\/or malpositioned kidney\/ureter in two fetuses. In conclusion, TGF\u2010\u03b21 mab produced no adverse maternal or embryo\u2010fetal findings in rats when administered \u226450 mg\/kg on GDs 6, 10, and 14. TGF\u2010\u03b21 mab did not demonstrate maternal toxicity or embryo\u2010fetal lethality at doses as high as 30 mg\/kg when administered on GDs 7, 12, 14, 16, and 18 in rabbits. Fetal growth and morphology were affected only at 30 mg\/kg; thus, the no observed adverse effect level was 3 mg\/kg in rabbits. The margin of safety for both rats and rabbits was \u226537\u2010fold the clinical exposure level.<\/jats:p>","DOI":"10.1002\/bdrb.21182","type":"journal-article","created":{"date-parts":[[2016,8,13]],"date-time":"2016-08-13T03:30:36Z","timestamp":1471059036000},"page":"174-184","source":"Crossref","is-referenced-by-count":4,"title":["TGF\u2010\u03b21 monoclonal antibody: Assessment of embryo\u2010fetal toxicity in rats and rabbits"],"prefix":"10.1002","volume":"107","author":[{"given":"Kim G.","family":"Hilbish","sequence":"first","affiliation":[{"name":"Lilly Research Laboratories Corporate Center  Indianapolis IN USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jennifer A.","family":"Martin","sequence":"additional","affiliation":[{"name":"Lilly Research Laboratories Corporate Center  Indianapolis IN USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anja J.","family":"Stauber","sequence":"additional","affiliation":[{"name":"Lilly Research Laboratories Corporate Center  Indianapolis IN USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tammye L.","family":"Edwards","sequence":"additional","affiliation":[{"name":"WIL Research  Ashland OH USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"William J.","family":"Breslin","sequence":"additional","affiliation":[{"name":"Lilly Research Laboratories Corporate Center  Indianapolis IN USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2016,8,12]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM200005043421807"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.semnephrol.2007.02.009"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1097\/01.ASN.0000033611.79556.AE"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1002\/bdrb.21089"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0006-291X(02)02708-0"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.3109\/10520292609115636"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1080\/00401706.1964.10490181"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.2307\/2528490"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2005.02.047"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.carpath.2004.11.005"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/0925-4773(95)00464-5"},{"key":"e_1_2_8_13_1","unstructured":"Hoar R. 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