{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,13]],"date-time":"2025-10-13T19:40:53Z","timestamp":1760384453936},"reference-count":32,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2005,6,2]],"date-time":"2005-06-02T00:00:00Z","timestamp":1117670400000},"content-version":"vor","delay-in-days":4901,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Teratology"],"published-print":{"date-parts":[[1992,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>The embryotoxic and teratogenic potential of all\u2010<jats:italic>trans<\/jats:italic> retinoic acid was assessed following exposure prior to and during early organogenesis in the cynomolgus monkey <jats:italic>(Macaca fascicularis)<\/jats:italic>. Sixteen pregnant females were orally administered all\u2010<jats:italic>trans<\/jats:italic> retinoic acid (Tretinoin, Hoffmann\u2010La Roche) once daily from GD 10\u201320 and twice daily from GD 21\u201324 at three different dosages, 5 (n=9), 10 (n=6) and 20 mg\/kg (n=1). Adverse clinical signs resembling hypervitaminosis A were observed in one animal at 5 mg\/kg, in three animals at 10 mg\/kg, and in the animal treated with 20 mg\/kg all\u2010<jats:italic>trans<\/jats:italic> retinoic acid. Maternal weight loss was observed in the 10\u2010 and 20\u2010mg\/kg groups. A dose\u2010dependent increase in embryolethality was observed, with 22% (2\/9), 50% (3\/6), and 100% (1\/1) occurring at 5, 10, and 20 mg\/kg, respectively. The majority of embryonic deaths occurred between GD 16 and 20; the incidence of these early losses was higher than in historical and concurrent controls. No malformations, but a single growth\u2010retarded fetus, was observed in the 5\u2010mg\/kg group. Craniofacial malformations, consisting of external ear defects, mandibular hypoplasia, cleft palate, and temporal bone abnormalities, were seen in three viable fetuses in the 10\u2010mg\/kg group. Skeletal variations were common to the majority (70%, 7\/10) of viable fetuses in both dose groups and were increased relative to historical controls (32%, 25\/77). Unlike previous studies with 13\u2010<jats:italic>cis<\/jats:italic>\u2010retinoic acid during the pre\u2010 and early organogenic stages of development (Hummler et al., Teratology 42:263\u2010272, 1990), no thymic hypo\u2010 or aplasia or heart anomalies were observed, which may be attributable to the slightly longer 13\u2010<jats:italic>cis<\/jats:italic> retinoic acid treatment period, i.e., GD 10\u201327. However, external ear and temporal bone defects were common to both all\u2010<jats:italic>trans<\/jats:italic> and 13\u2010<jats:italic>cis<\/jats:italic> retinoic acid. The similarity observed in the malformation syndrome induced by both all\u2010<jats:italic>trans<\/jats:italic> and 13\u2010<jats:italic>cis<\/jats:italic> retinoic acid in the cynomolgus monkey and 13\u2010<jats:italic>cis<\/jats:italic> retinoic acid embryopathy in humans supports this macaque species as a model for further developmental toxicity studies of vitamin A\u2010related compounds.<\/jats:p>","DOI":"10.1002\/tera.1420450106","type":"journal-article","created":{"date-parts":[[2005,6,11]],"date-time":"2005-06-11T15:48:54Z","timestamp":1118504934000},"page":"65-74","source":"Crossref","is-referenced-by-count":51,"title":["Teratogenicity of all\u2010<i>trans<\/i> retinoic acid during early embryonic development in the cynomolgus monkey (<i>Macaca fascicularis<\/i>)"],"prefix":"10.1002","volume":"45","author":[{"given":"Andrew G.","family":"Hendrickx","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hans","family":"Hummler","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2005,6,2]]},"reference":[{"key":"e_1_2_1_2_1","unstructured":"Archival Data from Hoffmann\u2010La Roche(1977 and 1980)."},{"key":"e_1_2_1_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/0300-483X(89)90161-3"},{"key":"e_1_2_1_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/0002-9343(89)90386-0"},{"key":"e_1_2_1_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/0896-6273(89)90066-4"},{"key":"e_1_2_1_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/0041-008X(87)90253-5"},{"key":"e_1_2_1_7_1","first-page":"447A","article-title":"Pharmacokinetics of 13\u2010cis\u2010 and all\u2010trans\u2010retinoic acid in the cynomolgus monkey","volume":"39","author":"Creech Kraft J.","year":"1989","journal-title":"Teratology"},{"key":"e_1_2_1_8_1","volume-title":"Biostatistics: A Foundation for Analysis in the Health Sciences, 3rd Ed","author":"Daniel W. 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