{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T17:31:21Z","timestamp":1760203881857},"reference-count":23,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2003,10,23]],"date-time":"2003-10-23T00:00:00Z","timestamp":1066867200000},"content-version":"vor","delay-in-days":22,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Birth Defects Research Pt B"],"published-print":{"date-parts":[[2003,10]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p><jats:bold>BACKGROUND:<\/jats:bold> Hoshi et al. [Hoshi et al. J Toxicol Sci 10(Suppl):187\u2013255, 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\u2010 and postnatal study. The authors concluded that there were no compound\u2010related findings. In the cesarean\u2010section 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\u2010related increase in clubfoot was not specifically addressed. In the rabbit teratology study, the number of litters evaluated (12\u201313 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. <jats:bold>METHODS:<\/jats:bold> Groups of 20 pregnant Sprague\u2013Dawley rats and New Zealand White rabbits were dosed with 0, 50, 150, 625, or 2500 mg\/kg HPMCAS from gestational day (GD) 6\u201317 or GD 7\u201319 for rats and rabbits, respectively. Fetuses were collected by cesarean section and examined for external, visceral and skeletal development. <jats:bold>RESULTS:<\/jats:bold> 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. <jats:bold>CONCLUSIONS:<\/jats:bold> 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. <jats:italic>Birth Defects Res B<\/jats:italic> 68:421\u2013427, 2003. \u00a9 2003 Wiley\u2010Liss, Inc.<\/jats:p>","DOI":"10.1002\/bdrb.10039","type":"journal-article","created":{"date-parts":[[2003,10,24]],"date-time":"2003-10-24T08:10:14Z","timestamp":1066983014000},"page":"421-427","source":"Crossref","is-referenced-by-count":6,"title":["Embryo\/fetal development studies with hydroxypropyl methylcellulose acetate succinate (HPMCAS) in rats and rabbits"],"prefix":"10.1002","volume":"68","author":[{"given":"Gregg D.","family":"Cappon","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tammye L.","family":"Fleeman","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Meredith 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