University of Massachuses Boston ScholarWorks at UMass Boston Graduate Doctoral Dissertations Doctoral Dissertations and Masters :eses 6-1-2015 Examining the Toxicity, Exposure, and Regulatory Approach to Potential Human Health Risks of the Algal Toxin Domoic Acid omas H. Angus University of Massachuses Boston Follow this and additional works at: h;p://scholarworks.umb.edu/doctoral_dissertations Part of the Environmental Sciences Commons, Public Health Commons, and the Toxicology Commons Recommended Citation Angus, :omas H., "Examining the Toxicity, Exposure, and Regulatory Approach to Potential Human Health Risks of the Algal Toxin Domoic Acid" (2015). Graduate Doctoral Dissertations. Paper 201. :is Open Access Dissertation is brought to you for free and open access by the Doctoral Dissertations and Masters :eses at ScholarWorks at UMass Boston. It has been accepted for inclusion in Graduate Doctoral Dissertations by an authorized administrator of ScholarWorks at UMass Boston. For more information, please contact [email protected]. EXAMINING THE TOXICITY, EXPOSURE, AND REGULATORY APPROACH TO POTENTIAL HUMAN HEALTH RISKS OF THE ALGAL TOXIN DOMOIC ACID A Dissertation Presented by THOMAS H. ANGUS Submitted to the Office of Graduate Studies, University of Massachusetts Boston, in partial fulfillment of the requirements for the degree of DOCTOR OF PHILOSOPHY June 2015 Environmental, Earth, and Ocean Sciences Program © 2015 by Thomas H. Angus All rights reserved EXAMINING THE TOXICITY, EXPOSURE, AND REGULATORY APPROACH TO POTENTIAL HUMAN HEALTH RISKS OF THE ALGAL TOXIN DOMOIC ACID A Dissertation Presented by THOMAS H. ANGUS Approved as to style and content by: ________________________________________________ Robert Bowen, Associate Professor Chairperson of Committee ________________________________________________ David Terkla, Dean Member ________________________________________________ Helen Poynton, Assistant Professor Member _______________________________________________ Michael Hutcheson, PhD., Massachusetts Department of Environmental Protection Member _________________________________________ Ellen Douglas, Graduate Program Director School for the Environment _________________________________________ Robyn Hannigan, Dean School for the Environment ABSTRACT EXAMINING THE TOXICITY, EXPOSURE, AND REGULATORY APPROACH TO POTENTIAL HUMAN HEALTH RISKS OF THE ALGAL TOXIN DOMOIC ACID June 2015 Thomas H. Angus, B.S., Tufts University M.S.P.H., University of North Carolina Chapel Hill Ph.D., University of Massachusetts Boston Directed by Professor Robert Bowen Domoic acid is a neurotoxin produced by the marine diatom genus Pseudo-nitzschia and causes cell death primarily in the area of the brain responsible for long-term memory. The resulting severe illness has been termed amnesic shellfish poisoning. Domoic acid accumulates in shellfish and planktivorous fish that consume Pseudo-nitzschia, resulting in exposure to humans through consumption of planktivorous seafood. A regulatory standard in seafood was developed shortly after its discovery in 1987 to protect against acute effects. This regulatory standard has not been revised despite significant recent data in the scientific literature. This dissertation is divided into four sections: (1) an identification of anthropogenic and natural drivers of nutrient dynamics as well as social dynamics that can contribute to current and future exposure to domoic acid; (2) a review of the weight iv of evidence for revisiting the current regulatory standard based on recent low level chronic effects data in the toxicological literature, sensitive subpopulation information and long term seafood consumption data; (3) an analysis of monitoring data on the presence of Pseudo-nitzschia in ocean waters and domoic acid in seafood to examine spatial and temporal trends in human exposure; and (4) evaluation of the regulatory framework for natural toxins in seafood with domoic acid as an example. Nutrient and social dynamics have the potential to drive exposure in humans. Recent toxicological data are not reflected in the current standard as it is based on data for acute toxicity and protects against gross observable neurotoxicity rather than chronic effects. The recent literature has shown that exposure to domoic acid can result in more subtle physical and behavioral brain impacts that have been observed in limited human data as well as extensive data on laboratory animals and marine mammals. Toxicological studies have demonstrated that certain groups such as the young, and the elderly are much more sensitive to domoic acid exposure. This is of particular concern because monitoring data for domoic acid in seafood are limited and may not ensure protection of the public. Pseudo-nitzschia is ubiquitous both temporally and spatially. This dissertation concludes that the regulatory approach warrants revisiting. v ACKNOWLEDGEMENTS It takes a village to raise a child, and it also takes a village to complete a dissertation. I would like to thank my wife Amy, my children Sienna and Griffin, and my parents for their love and support during this lengthy journey. During this process my wife and I have both worked full time, so this dissertation was the product of many nights and weekends. This dissertation would not have been possible without my wife picking up the slack in family responsibilities and allowing me time to research and write. I would like to thank Marin Kress for providing support during the proposal process and commenting on early drafts. Finally, I would like to thank my committee including David Terkla, Helen Poynton, Michael Hutcheson, and especially Robert Bowen for their commitment of precious time, and their imparting of invaluable expertise. vi TABLE OF CONTENTS ACKNOWLEDGEMENTS ........................................................................... vi LIST OF TABLES ......................................................................................... viii LIST OF FIGURES ....................................................................................... x LIST OF ACRONYMS ................................................................................. xiii CHAPTER INTRODUCTION ............................................................................. 1 1. THE HUMAN DYNAMICS OF DOMOIC ACID ...................... 8 2. TOXICITY ASSESSMENT ......................................................... 42 3. DOMOIC ACID EXPOSURE ...................................................... 127 4. CHARACTERIZATION AND MANAGEMENT....................... 208 CONCLUSION .................................................................................. 253 APPENDIX A. PSEUDO-NITZSCHIA DATA FROM THE L4 LOCATION ................................................................................. 264 B. CHANGE IN SEA SURFACE TEMPERATURE DATA (±DEGREE CELSIUS) USED IN THE ENSO ANALYSIS ................................................................... 294 C. WASHINGTON STATE RAZOR CLAM DOMOIC ACID DATA .......................................................... 296 ENDNOTES................................................................................................... 306 BIBLIOGRAPHY .......................................................................................... 334 vii LIST OF TABLES Table Page 1-1. World Marine Seafood Production ............................................. 37 1-2. Shellfish Wild Capture and Aquaculture Production ................. 39 2-1. Uncertainty and Modifying Factors Used in Deriving a Reference Dose ...................................................................... 51 2-2. Effects in Humans from Environmental Exposures ................... 61 2-3. Effects in Adult Animals ............................................................ 65 2-4. Behavioral Effects from In Utero Exposures ............................. 68 2-5. Behavioral Effects from Postnatal Exposures ............................ 71 2-6. Structural Changes from Postnatal Exposures............................ 77 2-7. Domoic Acid Effects in Marine Mammals and Birds ................ 85 2-8. Studies Available to Derive a Chronic Seafood Consumption Rate .................................................................................. 111 2-9. Comparison of Currently Available Acute Reference Doses ..... 115 2-10. Studies Available to Derive a Chronic Reference Dose ........... 118 2-11. Range of Possible Chronic Action Levels ................................ 123 3-1. Summary of Pseudo-nitzschia Observations 1992-2009 at Location L4 ............................................................................ 141 3-2. Regression Summary for Total Pseudo-nitzschia and Nutrients 172 3-3. Partial and Semi-Partial Correlations Between Pseudo-nitzschia and Nutrients.............................................. 173 3-4. Lag Analysis for Ammonia ........................................................ 174 viii LIST OF TABLES Table Page 3-5. Summary of Published Data on Domoic Acid in Seafood ......... 190 4-1. Tolerances for Seafood ............................................................... 214 4-2. FDA Seafood Action Levels for Natural Toxins ........................ 217 4-3. Natural Toxins Seafood Regulatory Levels................................ 219 4-4. Reportable Illnesses for Natural Toxins in Seafood ................... 228 4-5. Top Sources of Imported United States Seafood........................ 245 ix LIST OF FIGURES Figure Page 1-1. Total World Marine Seafood Production ..................................