PMID- 14745992
OWN - NLM
STAT- MEDLINE
DCOM- 20040702
LR  - 20060315
IS  - 1542-9733 (Print)
IS  - 1542-9733 (Linking)
VI  - 68
IP  - 5
DP  - 2003 Oct
TI  - Embryo/fetal development studies with hydroxypropyl methylcellulose acetate 
      succinate (HPMCAS) in rats and rabbits.
PG  - 421-7
AB  - BACKGROUND: Hoshi et al. [Hoshi et al. J Toxicol Sci 10(Suppl):187-255, 
      1985a,b,c,d] evaluated the potential for hydroxypropyl methylcellulose acetate 
      succinate (HPMCAS) to produce developmental and reproductive toxicity in a series 
      of studies that included rat and rabbit teratology studies, a rat fertility 
      study, and a rat peri- and postnatal study. The authors concluded that there were 
      no compound-related findings. In the cesarean-section phase of the rat teratology 
      study, however, clubfoot was reported for 0.8, 2.1, 5.5, and 4.1% of fetuses in 
      the control, 625, 1250, and 2500 mg/kg groups, respectively. There were no 
      significant increases in external anomalies, but the apparent dose-related 
      increase in clubfoot was not specifically addressed. In the rabbit teratology 
      study, the number of litters evaluated (12-13 per group) was not consistent with 
      current regulatory guidelines. Therefore, to definitively establish the potential 
      of HPMCAS to produce developmental toxicity, embryo/fetal development studies 
      were carried out in rats and rabbits. METHODS: Groups of 20 pregnant 
      Sprague-Dawley rats and New Zealand White rabbits were dosed with 0, 50, 150, 
      625, or 2500 mg/kg HPMCAS from gestational day (GD) 6-17 or GD 7-19 for rats and 
      rabbits, respectively. Fetuses were collected by cesarean section and examined 
      for external, visceral and skeletal development. RESULTS: No developmental 
      toxicity was observed as a result of HPMCAS exposure demonstrating that maternal 
      HPMCAS exposure during gestation does not induce developmental anomalies. There 
      were no findings of clubfoot or other limb anomalies in these studies at dose 
      levels equivalent to those that were previously associated with a possible 
      increase in clubfoot. CONCLUSIONS: The conclusion of the earlier study indicating 
      that treatment with HPMCAS at doses up to and including 2500 mg/kg did not 
      produce developmental toxicity was confirmed with these studies. It is likely 
      that the clubfoot noted in the earlier rat teratology study was a misdiagnosis or 
      artifact.
CI  - Copyright 2003 Wiley-Liss, Inc.
FAU - Cappon, Gregg D
AU  - Cappon GD
AD  - Pfizer Global Research and Development, Building 274 MS 1260, Eastern Point Road, 
      Groton, CT 06340, USA. gregg_d_cappon@groton.pfizer.com
FAU - Fleeman, Tammye L
AU  - Fleeman TL
FAU - Rocca, Meredith S
AU  - Rocca MS
FAU - Cook, Jon C
AU  - Cook JC
FAU - Hurtt, Mark E
AU  - Hurtt ME
LA  - eng
PT  - Journal Article
PL  - United States
TA  - Birth Defects Res B Dev Reprod Toxicol
JT  - Birth defects research. Part B, Developmental and reproductive toxicology
JID - 101155115
RN  - 0 (Teratogens)
RN  - 71138-97-1 (hydroxypropylmethylcellulose acetate succinate)
RN  - 9004-67-5 (Methylcellulose)
SB  - IM
MH  - Animals
MH  - Animals, Newborn
MH  - Clubfoot/chemically induced
MH  - Dose-Response Relationship, Drug
MH  - Embryonic and Fetal Development/*drug effects
MH  - Female
MH  - Methylcellulose/administration & dosage/*analogs & derivatives/*toxicity
MH  - Pregnancy
MH  - Rabbits
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Reproduction/drug effects
MH  - Teratogens/toxicity
EDAT- 2004/01/28 05:00
MHDA- 2004/07/03 05:00
CRDT- 2004/01/28 05:00
PHST- 2004/01/28 05:00 [pubmed]
PHST- 2004/07/03 05:00 [medline]
PHST- 2004/01/28 05:00 [entrez]
AID - 10.1002/bdrb.10039 [doi]
PST - ppublish
SO  - Birth Defects Res B Dev Reprod Toxicol. 2003 Oct;68(5):421-7. doi: 
      10.1002/bdrb.10039.