Palatal ruga anomaly induced by all-trans-retinoic acid in the Crj:SD rat: possible warning sign of teratogenicity.
We have reported that the critical period for cleft palate formation by all-trans-retinoic acid (RA) is on gestation day 14 in rats, and classified abnormal patterns of palatal rugae into minor variations and anomalous patterns. In this study, we examined the dose-response relationship for cleft palate and an anomalous pattern of palatal rugae formation and discussed the toxicologic significance of the palatal ruga anomaly as an indicator of teratogenicity. The ED(50) values for cleft palate and anomalous pattern were calculated to be 43.6 and 4.95 mg/kg, respectively. The results clearly show that anomalous rugal patterns occur in the fetuses from litters receiving RA at a lower dose than cleft palate induction; the anomalous ruga pattern is thus more sensitive than cleft palate induction. The anomalies of palatal rugae could be taken as a warning sign or an indicator of teratogenicity of a drug.
Ikemi
N
N
Agrochemical Development Department, Otsuka Chemical Co., Ltd., 3-2-27, Ote-dori, Chuo-ku, 540-0021, Osaka, Japan. naoki.ikemi@otsukac.co.jp
Otani
Y
Y
Ikegami
T
T
Yasuda
M
M
D000014:Abnormalities, Drug-Induced; D000818:Animals; D002972:Cleft Palate / Q000139:chemically induced*; D004305:Dose-Response Relationship, Drug; D005260:Female; D010159:Palate / Q000002:abnormalities*; D011247:Pregnancy; D051381:Rats; D017207:Rats, Sprague-Dawley; D014212:Tretinoin / Q000633:toxicity*
D014212:Tretinoin