title: Defining critical periods for itraconazole-induced cleft palate, limb defects and axial skeletal malformations in the mouse.
abstract: The main aim of the study was to identify the critical periods of susceptibility for itraconazole-mediated teratogenesis in the mouse. Pregnant ICR (CD-1) mice received a single oral administration of itraconazole at 50 mg/kg b.w., 150 mg/kg b.w. or 250 mg/kg b.w. on gestation day 8, 9, 10, 11 or 12. Control animals were administered with vehicle on gestation days 8-12. The gestational outcome was evaluated near term, on gestation day 18. Treatment-related morphological findings, as they can be evaluated by external, visceral and skeletal examination, mainly included cleft palate, limb defects and axial skeletal malformations. Cleft palate and limb defects resulted after single exposures between gestation days 9 and 11, with a tendency toward maximal response on gestation day 10. Significant incidences of axial skeletal defects were seen exclusively on gestation days 8 and 9. Exposure on gestation day 12 did not yield significant teratogenic responses. Cleft palate was the most sensitive teratogenic response, being the only developmental lesion associated to exposure to itraconazole at 150 mg/kg b.w.
authors.affiliation: Sezione di Ostetricia e Ginecologia, Dipartimento di Medicina e Scienze dell'Invecchiamento, Facoltà di Medicina e Chirurgia, Università G d'Annunzio, Chieti-Pescara, Ospedale SS Annunziata, Via dei Vestini, Chieti, Italy. tiboni@unich.it
authors.forename: Gian Mario
authors.initials: GM
authors.lastname: Tiboni
authors.forename: Francesca
authors.initials: F
authors.lastname: Marotta
authors.forename: Antonio
authors.initials: A
authors.lastname: Del Corso
authors.forename: Franca
authors.initials: F
authors.lastname: Giampietro
mesh_terms: D000015:Abnormalities, Multiple / Q000139:chemically induced* / Q000473:pathology*; D000818:Animals; D000935:Antifungal Agents / Q000633:toxicity*; D002972:Cleft Palate / Q000139:chemically induced*; D004305:Dose-Response Relationship, Drug; D005121:Extremities / Q000473:pathology; D005260:Female; D005865:Gestational Age; D017964:Itraconazole / Q000633:toxicity*; D051379:Mice; D008813:Mice, Inbred ICR; D009139:Musculoskeletal Abnormalities / Q000139:chemically induced* / Q000473:pathology; D011247:Pregnancy; D013723:Teratogens
chemical_list: D000935:Antifungal Agents; D013723:Teratogens; D017964:Itraconazole