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Abstract

Cyclopamine, the compound responsible for cyclopia in sheep upon maternal ingestion of Veratrum californicum, produced cyclopia and related cephalic malformations in rabbits when orally administered with CaCO3 as a stomach-acid buffer to prevent acid-induced conversion to veratramine, a compound devoid of similar teratogenic activity. The insult period was between days 6 and 9 of gestation. Both in vitro and in vivo experiments suggested the conversion of nonbuffered cyclopamine to veratramine under stomach-acid conditions.