PMID- 8475456
OWN - NLM
STAT- MEDLINE
DCOM- 19930520
LR  - 20220408
IS  - 0040-3709 (Print)
IS  - 0040-3709 (Linking)
VI  - 47
IP  - 1
DP  - 1993 Jan
TI  - Importance of early exposure to 13-cis retinoic acid to induce teratogenicity in 
      the cynomolgus monkey.
PG  - 37-45
AB  - The teratogenic potential of 13-cis retinoic acid (13-cis RA) was further 
      assessed in cynomolgus macaques (Macaca fascicularis) following exposure to two 
      different regimens during the preorganogenic period to determine the influence of 
      time of treatment on the 13-cis RA malformation syndrome established previously 
      (Hummler et al., Teratology, 42:263-272, 1990). In experiment (Exp) 1, 13-cis RA 
      was orally administered once daily (2.5 mg/kg) on gestational day (GD) 16-25 and 
      twice daily (2 x 2.5 mg/kg) on GD 26-27. In Exp 2, the same oral dose was 
      administered once daily on GD 10-20 and twice daily on GD 21-24. Although the ear 
      was affected at about the same incidence (6/9, 67%) in Exp 1 as previously 
      reported, the defects were less severe. Except for hypoplastic vermis of the 
      cerebellum (2/9, 22%), no other defects were seen. In Exp 2, the teratogenic 
      effects of 13-cis RA on the craniofacial skeleton (1/9, 11%), external ear (5/9, 
      56%), and heart (2/9, 22%) were similar to that reported by Hummler et al.; 
      however, no thymus or cerebellar malformations were observed. Analysis of the 
      three different treatments (GD 16-27 in Exp 1, GD 10-24 in Exp 2, and GD 10-27 in 
      Hummler et al.) suggests that the sensitive periods in the macaque are 1) 
      craniofacial skeleton and heart GD 10-24, 2) thymus and cerebellum > GD 24, and 
      3) external ear GD 16-24, although the defects are less severe following the 
      shorter exposure.(ABSTRACT TRUNCATED AT 250 WORDS)
FAU - Korte, R
AU  - Korte R
AD  - Hazleton Laboratories, Munster, Germany.
FAU - Hummler, H
AU  - Hummler H
FAU - Hendrickx, A G
AU  - Hendrickx AG
LA  - eng
PT  - Comparative Study
PT  - Journal Article
PL  - United States
TA  - Teratology
JT  - Teratology
JID - 0153257
RN  - EH28UP18IF (Isotretinoin)
SB  - IM
MH  - *Abnormalities, Drug-Induced/pathology
MH  - Animals
MH  - Dose-Response Relationship, Drug
MH  - Ear, External/abnormalities
MH  - Female
MH  - Gestational Age
MH  - Humans
MH  - Isotretinoin/administration & dosage/*toxicity
MH  - Macaca fascicularis
MH  - Maternal-Fetal Exchange
MH  - Pregnancy
MH  - Species Specificity
MH  - Syndrome
EDAT- 1993/01/01 00:00
MHDA- 1993/01/01 00:01
CRDT- 1993/01/01 00:00
PHST- 1993/01/01 00:00 [pubmed]
PHST- 1993/01/01 00:01 [medline]
PHST- 1993/01/01 00:00 [entrez]
AID - 10.1002/tera.1420470108 [doi]
PST - ppublish
SO  - Teratology. 1993 Jan;47(1):37-45. doi: 10.1002/tera.1420470108.