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EXPOSURE TO A P13KINASE INHIBITOR PRODUCED DYSMORPHOGENESIS IN NEURULATION-STAGED MOUSE EMBRYOS IN CULTURE
HUNTER, E. S., M. R. BLANTON, E. KAROLY, AND M. B. ROSEN. EXPOSURE TO A P13KINASE INHIBITOR PRODUCED DYSMORPHOGENESIS IN NEURULATION-STAGED MOUSE EMBRYOS IN CULTURE. Presented at Teratology Society Meeting, St. Petersburg, FL, June 26 - 30, 2005.
The haloacetic acids (HAA) are a family of chemicals that are drinking water disinfection byproducts. We previously reported that bromo- and chloro-acetic acids alter embryonic development when mouse conceptuses are directly exposed to these xenobiotics in whole embryo culture. Craniofacial dysmorphogenesis was observed in exposed embryos and a quantitative structure activity relationship (QSAR) for induction of cranial neural tube dysmorphogenesis was established. In the current study we evaluate the effects of exposing neurulation staged (3-6 somite pairs) CD-1 mouse conceptuses to bromochloro- (BCA), dibromochloro- (DBCA) and bromodichloro-acetic (BDCA) acids in whole embryo culture at concentrations ranging from 50-2500�M. Morphological development was assessed after a 26 hour exposure period. Exposure of conceptuses to these HAAs produced dysmorphogenesis including prosencephalic and pharyngeal arch hypoplasia as well as heart tube abnormalities. Benchmark concentrations for induction of neural tube dysmorphogenesis were 63, 500 and 536 �M for BCA, DBCA and BDCA, respectively. The QSAR previously developed for the bromo/chloro- HAAs correctly predicted that BCA was more potent than DBCA and BDCA. Additionally, the QSAR correctly predicted the relative potencies of these three chemicals within the broad class of brominated and chlorinated HAAs. This study describes the concentration dependent induction of dysmorphogenesis in whole embryo culture by three HAAs and demonstrates the ability of a QSAR to predict relative potencies within this family of xenobiotics.