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Fate and Transformation of a Conjugated Natural Hormone

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Fate and Transformation of a Conjugated Natural Hormone FATE AND TRANSFORMATION OF A CONJUGATED NATURAL HORMONE 17/J-ESTRADIOL-3-GLUCURONIDE IN SOIL-WATER SYSTEMS A Dissertation Submitted to the Graduate Faculty of the North Dakota State University of Agriculture and Applied Science By Suman Lal Shrestha In Partial Fulfillment of the Requirements for the Degree of DOCTOR OF PHILOSOPHY ~fajor Department: Civil Engineering September 20 I I Fargo. '.'\onh Dakota North Dakota State University Graduate School Title FATE AND T RA NSFOR!v1AT I0 N OF A CONJUGATED NATURAL HORMONE 17/3-ESTRA DIOL-3 -GLUCURONIDE IN SOIL-WATER SYSTEMS By Suman Lal Shrestha The Supervisory Committee certifies that this disquisition complies with North Dakota State University's regulations and meets the accepted standards for the degree of DOCTOR OF PHILOSOPHY North Dakota State University Libraries Addendum To protect the privacy of individuals associated with the document, signatures have been removed from the digital version of this document. ABSTRACT Shrestha, Suman Lal, Ph.D., Department of Civil Engineering, College of Engineering and Architecture, North Dakota State University, September 2011. Fate and Transformation of a Conjugated Natural Hormone l 7jf-Estradiol-3-Glucuronide in Soil-Water Systems. Major Professors: Dr. G. Padmanabhan and Dr. Francis X.M. Casey. The objectives of the study were to investigate the sorption and degradation behavior of a glucuronide conjugated natural hormone, l 7jf-estradiol-3-glucuronide (E2-3G), and the conjugate-derived estrogens in soil-water systems. The effects of soil organic matter content and microbial activity on the fate and sorption of E2-3G were investigated using soil-water batch experiments with natural and sterilized topsoil (0-6 cm) and !-.ubsoil ( 18-24 cm) from an agricultural farm. A radiolabeled version of E2-3G was synthesized using an immobilized-enzyme approach for conducting the fate and transformation experiment. The aqueous dissipation of 14C in the batch experiments followed a biphasic pattern, where there was an initial rapid dissipation phase followed by a second slower phase where apparent sorption equilibrium was achieved. Significant differences in total aqueous 14C dissipation were observed for the different initial concentrations for both soils. The pe1 sistence of intact E2-3G was exacerbated at higher initial concentrations. which may indicate the saturability of the enzymatic hydrolysis. Speciation analysis indicated that E2-3G metabolized into e!-.trone glucuronide (E l-3G ). E2. and estrone (EI). Other unidentified polar metabolites were detected and estriol (E3 J was not detected. The sorbed phase fraction contained EI and E2. Concentration of EI was at least 1.8 times greater than E2 in the sorbed phase of the natural topsoil. \vhile E2 concentration was greater in the sorbed phase of the subsoil. 111 Compared to the subsoil, more rapid E2-3G deconjugation in the topsoil was observed. which resulted in rapid aqueous phase dissipation dominated by aglycone (E2 and EI) hydrophobic sorption dynamics. In case of the subsoil, transformation of E2-3G to free estrogens was slower, and E2-3G transformation and sorption of aglycones were equivalent processes. For the topsoil and subsoils, the first 24 h and up to 14 d, respectively, were critical periods for the potential estrogenic contribution to the environment from intact glucuronide conjugates. The estrogenicity, expressed as E2 equivalent (EEQ) concentration, was calculated for the natural topsoil showing a maximum EEQ at 24 h (33 1 to 972 µg eq-E2 L~ ), and significant EEQ was observed even up to 28 days. A comprehensive kinetic biogeochemical model was developed to describe various non-equilibrium degradation and sorption processes of E2-3G and its metabolites that included the simultaneous chemical and biological transformation of the compounds and their mass exchanges between the aqueous phase and the reversible and irreversible sorption sites. The batch soil-water process parameters for E2-3G and its metabolites were uniquely identified by optimizing all the experiments simultaneously, using a global optimization strategy. The E2-3G hydrolysis in the na~ural topsoil was two orders of magnitude greater than the subsoil. The sorption capacity for E2-3G was one and three orders of magnitude lower than the E2 in the topsoil and subsoils. respectively. This study shows that estrogen conjugates may be significant contributors in the environmental detection of potent free estrogens. Agricultural application of manure containing conjugates. especially at the subsurface. may result in greater mobility of intact conjugates in the enYironment. I\' ACKNOWLEDGMENTS I would like to express my gratitude and sincere appreciation to my advisors Dr. G. Padmanabhan and Dr. Frank Casey, for their training. encouragement, supprn1, and faith during my graduate studies and graduate research for my Ph.D. I not only learned how to conduct a proper scientific study, but also learned how to aspire and achieve scientific research that is truly among the vanguard in the field of contaminant fate and transport in the environment. I would like to thank Dr. Heldur Hakk, Dr. David Smith, and Dr. Gerald Larsen (retired) of USDA Bio-sciences Research Laboratory who provided their laboratory space and equipment for my research and guided me at various steps. Along with learning the analytical techniques that were new to me, I also learned to work successfully in a truly multi-disciplinary research environment. I also thank them for providing their feedback in my manuscripts. I am also grateful for other members of my advisory committee, Dr. Eakalak Khan and Dr. Peter Oduor. for their comments and suggestions on my dissertation. I sincerely thank Colleen Pfaff. Dee Anne Ellig, B.trb Magelky (retired). Mike Giddings. Grant Harrington. Jason Holthw,en. Glenn Wittenberg (USDA-ARS). and Nathan Derby (Soil Science Department. NDSu) for their support in the laboratory work and IT support. I would also like to thank Dr. Jane \1. Schuh. Yet & \1icro Sciences at NDSU for helping me with the soil irradiation. I am grateful to Dr. Zhaosheng Fan. l'niversity of Alaska. Fairbanks. former student of my advisor Dr. Casey, for his help and suggestions in the modeling work. I also thank my re<,earch group at Soil Science \' Department in NDSU and my colleagues at the Environmental Lab for their suggestions and encouragements. This research was funded by grants from National Science Foundation under Grant No. 0730492. I was fortunate to be awarded with the prestigious Presidential Doctoral Fellowship and Frank Bain Doctoral Fellowship to pursue my graduate study at NDSU. I thank the Department of Civil Engineering and the Department of Soil Science at NDSU for providing me with all support. I am grateful to my mother, siblings, and extended families for their love and support. My sister-in-law Monishajoined us at NDSU for her master study program, and made us feel more at home. Lastly, I thank my wife Sangita Shrestha for her unwavering love, understanding, and support in all these years. \'I DEDICATION To my late father Mr. Punya Lal Shrestha, who had a dream to see me engaged in high academic endeavors. \'II TABLE OF CONTENTS ABSTRACT .......................................................................................................................... iii ACKNOWLEDGMENTS ...................................................................................................... V DEDICATION ..................................................................................................................... vii LIST OF TABLES ............................................................................................................... xii LIST OF FIGURES ............................................................................................................. xvi GENERAL INTRODUCTION ............................................................................................... I Organization of the Dissertation ................................................................................. 2 Literature Review ....................................................................................................... 3 Estrogens: Natural steroidal hormones ........................................................... 3 Sources of steroidal estrogens and their conjugates in the environment ........ 6 Ecotoxicology ............................................................................................... I 0 Fate and transport of estrogen conjugates ..................................................... 16 Research Gap ............................................................................................................ I 8 Dissertation Objective .............................................................................................. 19 PAPER 1. SYNTHESIS AND CHARACTERIZATION OF RADIOLABELED 17/J-ESTRADIOL CONJUGATES ...................................................................................... 20 Abstract ..................................................................................................................... 20 Introduction ............................................................................................................... 21 Experimental ............................................................................................................. 23 Materials ....................................................................................................... 23 Synthesis of 17
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