?url_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Adc&rft.relation=http%3A%2F%2Fd-scholarship-dev.library.pitt.edu%2F10546%2F&rft.title=Predicting+Biological+Degradation+and+Toxicity+of+Steroidal+Estrogens&rft.creator=Barr%2C+William&rft.description=This+study+was+to+construct+a+model+to+predict+a+variety+of+biological+transformations+of+Ethinylestradiol%0D%0A(EE2)+using+electronic+theory+and+to+analyze+the+estrogenic+potential+of+EE2+and+its+metabolites.+As+a%0D%0Asecondary+goal%2C+Frontier+Electron+Density+(FED)+theory+was+applied+to+the+natural+steroidal+estrogens%2C%0D%0Aestrone+(E1)%2C+estradiol+(E2)+and+estriol+(E3)+to+determine+if+similar+initiating+reactions+could+be+expected.%0D%0AElectron+density+profiles+were+calculated+for+EE2+metabolites+to+determine+possible+metabolic+pathways%0D%0Aup+to+the+cleavage+of+the+first+ring.+The+pathways+predicted+in+this+study+assume+that+enzymes+commonly%0D%0Afound+in+wastewater+treatment+systems+will+be+available+to+attack+EE2+and+each+metabolite.+Predictive%0D%0Apathways+were+generated+for+EE2+based+on+the+electron+density+and+well+established+degradation+rules.+A%0D%0Anumber+of+metabolites+were+shown+to+be+consistent+with+FED+theory.%0D%0AThere+are+many+methods+available+for+effectively+calculating+the+electron+density+of+a+given+molecule.%0D%0ACalculations+were+carried+out+on+the+Pittsburgh+Supercomputer+(PSC)+using+the+computational+chemistry%0D%0Asoftware+Gaussian+03.+Two+molecular+orbital+theories+available+for+use+in+Gaussian+03+were+used+and%0D%0Aresults+compared+to+determine+if+the+level+of+theory+significantly+affected+the+accuracy+of+the+electron%0D%0Adensity+calculations.+In+the+beginning+of+this+study+only+one+theory+was+used+but+after+studying+the%0D%0Aavailable+theories+in+more+detail+I+implemented+a+theory+that+was+shown+to+be+more+accurate+in+literature.%0D%0AUsing+this+information+and+well+established+degradation+rules%2C+metabolic+pathways+leading+up+to+the+first%0D%0Aring+cleavage+were+predicted.+Experimentally+measured+metabolites+appear+in+the+predicted+pathways.%0D%0AIn+order+to+evaluate+the+environmental+impacts+of+steroidal+estrogens+and+their+subsequent+metabolites+the%0D%0Aestrogenic+potential+is+calculated+using+chemaxon+software.+The+estrogenic+potential+was+estimated+for%0D%0AEE2+and+each+of+its+metabolites+both+predicted+and+experimental+as+well+as+E1%2C+E2+and+E3+and+known%0D%0Aexperimentally+measured+metabolites+that+are+similar+to+EE2.+In+all+cases+the+estrogenic+potential+of+the%0D%0Ametabolites+indicate+that+they+have+a+lower+toxicity+than+the+parent+compounds+but+may+still+retain%0D%0Aestrogenic+potential+after+biotransformation.&rft.date=2012-01-30&rft.type=University+of+Pittsburgh+ETD&rft.type=PeerReviewed&rft.format=application%2Fpdf&rft.language=en&rft.identifier=http%3A%2F%2Fd-scholarship-dev.library.pitt.edu%2F10546%2F1%2FBarrWJFall2011.pdf&rft.identifier=++Barr%2C+William++(2012)+Predicting+Biological+Degradation+and+Toxicity+of+Steroidal+Estrogens.++Master's+Thesis%2C+University+of+Pittsburgh.++++(Unpublished)++