PMID- 2274892
OWN - NLM
STAT- MEDLINE
DCOM- 19910228
LR  - 20131121
IS  - 0040-3709 (Print)
IS  - 0040-3709 (Linking)
VI  - 42
IP  - 3
DP  - 1990 Sep
TI  - Induction of malformations in the cynomolgus monkey with 13-cis retinoic acid.
PG  - 263-72
AB  - The embryotoxic and teratogenic potential of 13-cis retinoic acid was assessed in 
      the cynomolgus macaque (Macaca fascicularis). A total of 41 animals was orally 
      administered 13-cis retinoic acid in four sequential experiments. In Exp. 1 three 
      dose levels, 2, 10, and 25 mg/kg, were administered on gestational day (GD) 
      18-28; 5 mg/kg was administered as an equally divided dose twice daily in Exp. 2 
      and 3 on GD 21-24 and on GD 25-27, respectively; in Exp. 4 the drug was 
      administered at 2.5 mg/kg once daily from GD 10 to 25 and twice daily (2 x 2.5 
      mg/kg) on GD 26 and 27. Maternal death and toxicity, manifested as reduction in 
      maternal weight and food consumption, and diarrhea, was observed in Exp. 1 in all 
      three dose groups. No significant maternal toxicity was observed in the treatment 
      groups in Exp. 2, 3, and 4 or in the control group. The primary manifestation of 
      developmental toxicity was embryolethality in Exp. 1 and 2. The incidence of 
      embryonic deaths in Exp. 3 was comparable to the historical controls. No 
      malformations in GD 100 fetuses were observed in Exp. 1, 2, and 3. In Exp. 4, 
      five of seven fetuses (71%) had malformations of both external ears, four of 
      seven fetuses (57%) exhibited hypo- or aplasia of the thymus, and two of seven 
      (29%) had malformations (transposition of the great vessels, ventricular septal 
      defect) of the heart. The teratogenic dose for the cynomolgus monkey in the 
      present study was lower than that reported for all other experimental species. 
      Although central nervous system and craniofacial defects were not observed, the 
      incidence of ear and thymus defects was similar to that reported for the human. 
      The cardiovascular defects resembled those reported clinically, but the incidence 
      was lower in the cynomolgus monkey. The similarity in teratogenic sensitivity to 
      humans supports the use of the monkey as a model for developmental toxicity 
      studies of vitamin A-related compounds.
FAU - Hummler, H
AU  - Hummler H
AD  - F Hoffmann-La Roche Ltd., Basel, Switzerland.
FAU - Korte, R
AU  - Korte R
FAU - Hendrickx, A G
AU  - Hendrickx AG
LA  - eng
PT  - Journal Article
PL  - United States
TA  - Teratology
JT  - Teratology
JID - 0153257
RN  - 0 (Teratogens)
RN  - 5688UTC01R (Tretinoin)
RN  - EH28UP18IF (Isotretinoin)
SB  - IM
MH  - Abnormalities, Drug-Induced/*etiology
MH  - Animals
MH  - Dose-Response Relationship, Drug
MH  - Ear/abnormalities
MH  - Female
MH  - Fetus
MH  - Isotretinoin/*toxicity
MH  - Macaca fascicularis
MH  - Organ Specificity
MH  - Pregnancy
MH  - *Teratogens
MH  - Tretinoin/*toxicity
EDAT- 1990/09/01 00:00
MHDA- 1990/09/01 00:01
CRDT- 1990/09/01 00:00
PHST- 1990/09/01 00:00 [pubmed]
PHST- 1990/09/01 00:01 [medline]
PHST- 1990/09/01 00:00 [entrez]
AID - 10.1002/tera.1420420310 [doi]
PST - ppublish
SO  - Teratology. 1990 Sep;42(3):263-72. doi: 10.1002/tera.1420420310.