W&M ScholarWorks Dissertations, Theses, and Masters Projects Theses, Dissertations, & Master Projects 2002 Predicting metal interactions with a novel quantitative ion character -activity relationship (QICAR) approach David R. Ownby College of William and Mary - Virginia Institute of Marine Science Follow this and additional works at: https://scholarworks.wm.edu/etd Part of the Environmental Sciences Commons, and the Toxicology Commons Recommended Citation Ownby, David R., "Predicting metal interactions with a novel quantitative ion character -activity relationship (QICAR) approach" (2002). Dissertations, Theses, and Masters Projects. Paper 1539616800. https://dx.doi.org/doi:10.25773/v5-w1nf-pb08 This Dissertation is brought to you for free and open access by the Theses, Dissertations, & Master Projects at W&M ScholarWorks. It has been accepted for inclusion in Dissertations, Theses, and Masters Projects by an authorized administrator of W&M ScholarWorks. For more information, please contact [email protected]. Reproduced with with permission permission of the of copyright the copyright owner. owner.Further reproductionFurther reproduction prohibited without prohibited permission. without permission. PREDICTING METAL INTERACTIONS WITH A NOVEL QUANTITATIVE ION CHARACTER-ACTIVITY RELATIONSHIP (QICAR) APPROACH A Dissertation Presented to The Faculty of the School of Marine Science The College of William and Mary in Virginia In Partial Fulfillment Of the Requirements for the Degree of Doctor of Philosophy by David R. Ownby 2002 Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. APPROVAL SHEET This dissertation is submitted in partial fulfillment of the requirements for the degree of Doctor of Philosophy David R. Ownby^' Approved, May 2002 / r , V v t ( n i t Michael C. Newman, Ph.D. Committee Chairman/Advisor \ k * U J L GC . l . Michael A. Unger, Ph.D. ' f e j L , ___ ert J. D r-% W. Ride, Ph.D. fans Carter, Ph.D. Medical College of Virginia Virginia Commonwealth University Richmond, Virginia Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. TABLE OF CONTENTS Page ACKNOWLEDGMENTS........................................................................................ v LIST OF TABLES.................................................................................................... vi LIST OF FIGURES .................................................................................................. vii ABSTRACT............................................................................................................... viii CHAPTER I. Introduction ......................................................................................... 2 A. Models for prediction of toxicity ................................................................. 3 1. SARs and QSARs............................................................................... 3 2. ICARs and QICARs............................................................................ 5 B. Approaches to mixtures ............................................................................. 9 1 .Similar Action........................................................................................ 10 2.lndependent Action .............................................................................. 11 C. Metal Ion Characteristics .......................................................................... 12 1. Definitions/Explanations of characteristics ...................................... 12 2. Chemical speciation will not improve mixture prediction in this study..................................................................................... 15 D. Why Bacterial Luminescence? ................................................................. 17 1. History.................................................................................................. 17 2. Utility.................................................................................................... 18 3. Metabolic pathways ........................................................................... 18 4. Comparison to other standard toxicity tests .................................... 19 F. Caenorhabditis elegans............................................................................. 20 G. Statement of Hypothesis to be Tested and Objectives of Research ............................................................................................. 22 CHAPTER II. Predicting Binary Interactions with the Microtox® System 27 A. Introduction ................................................................................................. 27 B. Methods...................................................................................................... 29 1. Calculation of single metal effect concentrations .......................... 29 2. Binary mixture tests.......................................................................... 30 3. Statistical analyses ........................................................................... 30 C. Results......................................................................................................... 31 1. Single metal Microtox® tests ............................................................ 31 2. Microtox® mixture tests ..................................................................... 31 D. Discussion .................................................................................................. 32 Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. CHAPTER III. Predicting Binary Interactions with Caenorhabditis elegans..........................................................................................41 A. Introduction .................................................................................................. 41 B. Methods....................................................................................................... 43 1. Test media and solution preparation................................................ 43 2. Experimental design and test procedure .......................................... 44 3. Calculation of single metal effect concentrations .............................44 4. Binary mixture tests.............................................................................45 5. Statistical analyses..............................................................................45 6 . Barium and potassium interaction test.............................................. 45 C. Results.........................................................................................................47 1. Single metal C. elegans tests............................................................ 47 2. C. elegans mixture tests..................................................................... 47 3. QICAR Model...................................................................................... 47 4. Barium and potassium interaction.....................................................48 D. Discussion ................................................................................................... 48 CHAPTER IV. The Toxic Units Concept: Does it Add Up? ................................. 59 A. Introduction .................................................................................................. 59 B. Methods....................................................................................................... 62 C. Results........................................................................................................ 63 D. Discussion ................................................................................................... 64 CHAPTER V. Summary and Conclusions ............................................................ 74 APPENDIX A ...........................................................................................................78 APPENDIX B ...........................................................................................................84 LITERATURE CITED ..............................................................................................89 VITA ...........................................................................................................................98 iv Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. ACKNOWLEDGMENTS I gratefully acknowledge the guidance and support of my major professor Dr. Michael C. Newman throughout my VIMS experience. His honesty about the challenges of mixture research from day one has been appreciated. I wish to thank Dr. Michael A. Unger for his friendship and advice both on my dissertation research and on other collaborations. Dr. W. Hans Carter was generous with his time and statistical advice on the design of this project and gave me confidence that my methods were correct. I also wish to thank my other Advisory Committee members Dr. Robert J. Diaz and Dr. Gary W. Rice for their input and reviews of this manuscript. Several members of the VIMS community loaned equipment or made laboratory space available for my project. I would especially like to thank Dr. Robert C. Hale for loan of the Microtox* toxicity analyzer and Dr. Howard Kator for allowing me to use his lab and autoclave for preparation of media and plates for the C. elegans exposures. Additionally, Dr. Phillip L. Williams welcomed me into his lab at University of Georgia and provided