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RECORD NUMBER: 3 OF 6

OLS Field Name OLS Field Data
Main Title Developmental Toxicity and Structure-Activity Relationships of Aliphatic Acids, Including Dose-Response Assessment of Valproic Acid in Mice and Rats.
Author Narotsky, M. G. ; Francis, E. Z. ; Kavlock, R. J. ;
CORP Author ManTech Environmental Technology, Inc., Research Triangle Park, NC.;Health Effects Research Lab., Research Triangle Park, NC.
Publisher cFeb 94
Year Published 1994
Report Number EPA-68-D20056 ;EPA-68-02-4450; EPA/600/J-94/328;
Stock Number PB94-197084
Additional Subjects Toxicity ; Aliphatic acids ; Valproic acid ; Rats ; Biological effects ; Drug-induced abnormalities ; Maternal health ; Fetal development ; Oral administration ; Acute exposure ; Mice ; Teratogens ; Assays ; Embryos ; Skeleton ; Anticonvulsants ; Reprints ; Dipropyl acetate ; 2-Propylentanoic acid ; 2-Ethylhexanoic acid ; Structure-activity relationships
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NTIS  PB94-197084 Most EPA libraries have a fiche copy filed under the call number shown. Check with individual libraries about paper copy. NTIS 11/11/1994
Collation 18p
Abstract
The anticonvulsant valproic acid (VPA), or 2-propylpentanoic acid, is a short-chain aliphatic acid that is teratogenic in humans and rodents. VPA and 14 related chemicals were screened for developmental toxicity using the Chernoff/Kavlock assay. Sprague-Dawley rats were gavaged with the test agent in corn oil once daily organogensis. The dams were allowed to deliver and the pups were examined postnatally. Segment II studies were also conducted using VPA and pentanoic acid in rats, and with VPA in CD-1 mice. For both species, VPA caused transient maternal ataxia and developmental defects of the digits and, especially, the axial skeleton. Exencephaly, however, was seen only in mice. All congeners tested induced maternal respiratory effects and six compounds caused motor depression. These data indicate a broader specificity for activity in the maternal system than in the embryo and suggest differing mechanisms for the two effects.