{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,3]],"date-time":"2026-10-03T18:08:42Z","timestamp":1791050922470,"version":"4.1.0"},"reference-count":31,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2009,3,19]],"date-time":"2009-03-19T00:00:00Z","timestamp":1237420800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J of Applied Toxicology"],"published-print":{"date-parts":[[2009,7]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Cyclopamine, a steroidal alkaloid, from the plant <jats:italic>Veratrum californicum<\/jats:italic> is teratogenic, causing a range of different birth defects. The critical window for cyclopamine\u2010induced synophthalmia formation has been reported to be gestational day (GD) 14. The objectives of this study were to better describe cyclopamine\u2010induced craniofacial deformities, to better define the window of susceptibility to synophthalmia formation, and to characterize cyclopamine toxicokinetics in sheep. Ewes were dosed i.v. with purified cyclopamine for toxicokinetic analysis. Another four groups of ewes were dosed orally twice daily with 0.88\u00a0g\/kg of <jats:italic>V. californicum<\/jats:italic> on GD 13, 14 or 15 or consecutively on GD days 13\u201315. Pregnancy and pre\u2010partum fetal malformations were determined by ultrasound imaging on GD 60. At parturition lambs were assessed for gross malformations. The elimination half\u2010life of cyclopamine in ewes was determined to be 1.1\u00a0\u00b1\u00a00.1\u00a0h. The rapid clearance of cyclopamine indicates that ingestion of <jats:italic>V. californicum<\/jats:italic> must occur during a very narrow window for synophthalmia formation to occur. Ewes dosed with <jats:italic>V. californicum<\/jats:italic> on GD 13 or 14 had lambs with various craniofacial malformations including cyclopia, maxillary dysplasia and mandibular micrognathia. Ewes dosed on GD 15 delivered normal lambs. Ewes dosed consecutively on GD 13\u201315 were not pregnant at GD 60 and <jats:italic>Veratrum<\/jats:italic>\u2010induced embryonic death was assumed to be the cause. Interestingly, lambs with cyclopia were smaller, under\u2010developed and appeared premature even though their twin appeared fully developed. Initial evaluations suggest this was due to placental dysplasia. Published in 2009 by John Wiley &amp; Sons, Ltd.<\/jats:p>","DOI":"10.1002\/jat.1427","type":"journal-article","created":{"date-parts":[[2009,3,19]],"date-time":"2009-03-19T07:23:13Z","timestamp":1237447393000},"page":"414-421","source":"Crossref","is-referenced-by-count":50,"title":["Cyclopamine\u2010induced synophthalmia in sheep: defining a critical window and toxicokinetic evaluation"],"prefix":"10.1002","volume":"29","author":[{"given":"K. D.","family":"Welch","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"K. E.","family":"Panter","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S. T.","family":"Lee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"D. R.","family":"Gardner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"B. 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