Iowa State University Capstones, Theses and Retrospective Theses and Dissertations Dissertations 1993 Diagnosing hydrogen sulfide ot xicosis with a silver/ sulfide ion-selective electrode Scott Thompson Witte Iowa State University Follow this and additional works at: https://lib.dr.iastate.edu/rtd Part of the Medical Toxicology Commons, Toxicology Commons, Veterinary Pathology and Pathobiology Commons, and the Veterinary Toxicology and Pharmacology Commons Recommended Citation Witte, Scott Thompson, "Diagnosing hydrogen sulfide ot xicosis with a silver/sulfide ion-selective electrode " (1993). Retrospective Theses and Dissertations. 10199. https://lib.dr.iastate.edu/rtd/10199 This Dissertation is brought to you for free and open access by the Iowa State University Capstones, Theses and Dissertations at Iowa State University Digital Repository. 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Ann Arbor, MI 48106 Diagnosing hydrogen sulfide toxicosis with a silver/sulfide ion-selective electrode by Scott Thompson Witte A Dissertation Submitted to the Graduate Faculty in Partial Fulfillment of the Requirements for the Degree of DOCTOR OF PHILOSOPHY Department: Veterinary Pathology Interdepartmental Major: Toxicology Approved: Signature was redacted for privacy. fn Cha^ of Major \^ork Signature was redacted for privacy. ,yéxFor thethe InterdepartmentalI nterdepai Major Signature was redacted for privacy. For^e Major Department Signature was redacted for privacy. For the Graduate College Iowa State University Ames, Iowa 1993 ii it was the best of times, it was the worst of times, it was the age of wisdom, it was the age of foolishness, it was the epoch of belief, it was the epoch of incredulity, it was the season of Light, it was the spring of hope, it was the winter of despair. - Charles John Dickens A Tale of Two Cities iii TABLE OF CONTENTS Page LIST OF FIGURES viii LIST OF TABLES x ABSTRACT xi INTRODUCTION 1 SELECTED REVIEW OF LITERATURE 2 Hydrogen Sulfide 2 Properties 2 Sources 2 Ambient concentrations 5 Air quality standards 5 Pharmacodynamics 5 Absorption 5 Distribution 7 Metabolism 7 Oxidation 7 Methylation 7 Protein interactions 10 Others 10 Excretion 10 Toxicity 11 Lethal concentrations and doses 11 Toxicity factors 14 Dosage 14 Animal factors 14 Environmental factors 15 Classification 15 Definitions 15 Acute 15 Subacute 15 Chronic 15 iv Cumulative toxin or chronic toxicosis? 15 Acute and Subacute Effects on Selected Systems 17 Nervous system 17 Development 17 Function 17 Carotid chemoreceptors 19 Biochemistry 19 Neurotransmitters 22 Clinical signs and symptoms 23 Pathology 23 Respiratory system 25 Pulmonary edema 25 Function 26 Biochemistry 28 Clinical signs and symptoms 29 Pathology 29 Hematopoietic system 29 Blood proteins 29 Hemoglobin 29 Case Reports 32 Human exposure cases 32 Animal exposure cases 32 Confinement production units 32 Ruminants 46 Swine 46 Other species 46 Diagnosis of acute - subacute toxicosis 46 History and environment 46 Clinical signs and symptoms 47 Pathology 47 Ancillary procedures 48 V Qualitative analysis 48 Quantitative analysis 49 Gas chromatography 49 High-performance liquid chromatography 49 Gas dialysis / ion chromatography 50 Ion-selective electrodes 51 Microdiffusion analysis 53 Analysis of manure pit 54 Differential diagnoses 54 MATERIALS AND METHODS 55 Reagents 55 Commercially Available Apparatus 55 Procedures 56 Calibration of the standard sulfide solutions 56 Confirming the slope of response of the ISE 56 Calibration of the electrode pair 57 Sulfide measurement in samples 57 Data acquisition 57 Serum bottle storage system 59 Experimental design and statistical analysis 59 Experiments 59 Phase 1 : Measurement development 59 Selection of measurement equipment and environment 59 (experiment 1) Stability and storage of SAOB based sulfide solutions (experiment 2) 62 Bench-top versus controlled analysis conditions (experiment 3) 62 Development of a modified liter-beaker calibration (experiment 4) 67 Phase 2: Extraction development with aqueous media 67 Comparison of measurement volumes (experiment 5) 67 Determination of optimal extraction variables (experiment 6) 70 The effects of zinc preservation on extraction (experiment 7) 70 Phase 3: Method development with animal tissues 71 vi Anti-foaming agents (experiment 8) 71 Blood determinations - A (experiment 9) 71 Blood determinations - B (experiment 10) 72 Blood determinations - C (experiment 11) 72 Blood determinations - D (experiment 12) 72 Serum and plasma analysis (experiment 13) 72 Sulfide determination in clotted blood (experiment 14) 72 Analysis of acid-labile sulfide in solid tissues (experiment 15) 73 Phase 4: Development of exposure techniques 73 Stability of standardized sulfide injection solution (experiment 16) 73 pH adjustment of the sulfide injection solution (experiment 17) 74 Confirmation of sulfide concentration in syringe formulated solutions 74 (experiment 18) Inhalation chamber design and validation (experiment 19) 74 Phase 5: Animal exposures 86 Dose-relationship study (experiment 20) 86 Inhalation exposure (experiment 21) 87 Sample quality study (experiment 22) 87 RESULTS 88 Phase 1 : Measurement Development 88 Selection of measurement equipment and environment (experiment 1 ) 88 Stability and storage of SAOB based sulfide solutions (experiment 2) 92 Bench-top versus controlled analysis conditions (experiment 3) 92 Development of a modified liter-beaker calibration (experiment 4) 92 Phase 2: Extraction Development with Aqueous Media 98 Comparison of measurement volumes (experiment 5) 98 Determination of optimal extraction variables (experiment 6) 98 The effects of zinc preservation on extraction (experiment 7) 98 Phase 3: Method Development with Animal Tissues 101 Anti-foaming agents (experiment 8) 101 Blood determinations - A to D (experiments 9 through 12) 101 Serum and plasma analysis (experiment 13) 103 vii Sulfide determination in clotted blood (experiment 14) 104 Analysis of acid-labile sulfide in solid tissues (experiment 15) 104 Phase 4: Development of Exposure Techniques 104 Stability of standardized sulfide injection solution (experiment 16) 104 pH adjustment of the sulfide injection solution (experiment 17) 107 Confirmation of sulfide concentration in syringe formulated solutions 107 (experiment 18) Inhalation chamber design and validation (experiment 19) 107 Phase 5: Animal Exposures 111 Dose-relationship study (experiment 20) 111 Inhalation exposure (experiment 21 ) 111 Sample quality study (experiment 22) 113 DISCUSSION 116 CONCLUSIONS 131 BIBLIOGRAPHY 135 ACKNOWLEDGMENTS 153 APPENDIX A: CAUSES OF SUDDEN DEATH IN LIVESTOCK 155 APPENDIX B: MANUFACTURES AND SOURCES 166 APPENDIX C: DATA ACQUISITION SOFTWARE FOR THE CORNING 255 ION 169 ANALYZER APPENDIX D: CODE AND FORMULAS, BY CELL ADDRESSES, FOR THE 170 LOTUS 1-2-3 (VERSION 2.2) SPREADSHEET MONITORING PERFORMANCE OF THE ION-SELECTIVE ELECTRODES APPENDIX E: DERIVATION OF THE CALIBRATION EQUATION 173 APPENDIX F; CONCENTRATIONS OF ACID-LABILE SULFIDE RECOVERED 174 FROM RATS INJECTED WITH LETHAL LEVELS OF SULFIDE APPENDIX G: TISSUE ACID-LABILE SULFIDE FROM RATS EXPOSED TO 175 ROOM AIR OR ACUTELY TOXIC HYDROGEN SULFIDE CONCENTRATIONS viii LIST OF FIGURES Page Figure 1. The sulfur cycle illustrating hydrogen sulfide as a major product of 4 microbial metabolism Figure 2. Proposed metabolic pathways of sulfide in animals 8 Figure 3. Proposed hydrogen sulfide interactions with hemoglobin 31 Figure 4. Capping system used to seal serum bottles of standardized sulfide 60 solutions, extracted samples prior to analysis, or sulfide anti- oxidation buffer Figure 5. Circulating water bath system used to maintain uniform sample 63 temperature during