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Cyanobacterial toxins of drinking water supplies : cylindrospermopsins and microcystins Ian R.. The importance of cyanobacterial toxins in drinking water sources has been high-lighted by

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Cyanobacterial Toxins of Drinking Water Supplies

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Cyanobacterial Toxins of Drinking Water Supplies

CRC PR E S S

Boca Raton London New York Washington, D.C

Cylindrospermopsins and Microcystins

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This book contains information obtained from authentic and highly regarded sources Reprinted material

is quoted with permission, and sources are indicated A wide variety of references are listed Reasonable efforts have been made to publish reliable data and information, but the author and the publisher cannot assume responsibility for the validity of all materials or for the consequences of their use.

Neither this book nor any part may be reproduced or transmitted in any form or by any means, electronic

or mechanical, including photocopying, microfilming, and recording, or by any information storage or retrieval system, without prior permission in writing from the publisher.

The consent of CRC Press does not extend to copying for general distribution, for promotion, for creating new works, or for resale Specific permission must be obtained in writing from CRC Press for such copying.

Direct all inquiries to CRC Press, 2000 N.W Corporate Blvd., Boca Raton, Florida 33431

Trademark Notice: Product or corporate names may be trademarks or registered trademarks, and are used only for identification and explanation, without intent to infringe.

Visit the CRC Press Web site at www.crcpress.com

© 2005 by CRC Press

No claim to original U.S Government works International Standard Book Number 0-415-31879-3 Library of Congress Card Number 2004054551 Printed in the United States of America 1 2 3 4 5 6 7 8 9 0

Printed on acid-free paper

Library of Congress Cataloging-in-Publication Data

Falconer, Ian R.

Cyanobacterial toxins of drinking water supplies : cylindrospermopsins and microcystins Ian R Falconer.

p cm.

Includes bibliographical references and index.

ISBN 0-415-31879-3 (alk paper)

1 Cyanobacterial toxins 2 Microcystins 3 Cyanobacteria 4 Freshwater microbiology 5 Bacterial pollution of water I Title

QP632.C87F34 2004 615.9'52939—dc22

2004054551

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The importance of cyanobacterial toxins in drinking water sources has been high-lighted by the adoption of a provisional drinking water “Guideline Value” for micro-cystin-LR, one of the most abundant toxins, by the World Health Organization (WHO) A number of nations have now legislated a guideline for microcystins into their drinking water regulations, with the consequent need for monitoring and ana-lytical techniques The Chemical Safety Committee of the WHO also has under consideration a Guideline Value for cylindrospermopsin, the other most damaging cyanobacterial toxin

The need for careful study of the cyanobacterial toxins, their sources, and their removal from water supplies was emphasized by the substantial death toll among dialysis patients in Brazil who were accidentally treated with water containing these toxins Consumers of treated drinking water have also suffered injury due to micro-cystins and cylindrospermopsin in the water supply, as have people exposed through recreational activities

Two aspects of cyanobacterial toxicity that require substantial attention are the possible long-term effects on the population of exposure to low doses of the toxins and intermittent exposure to higher doses In addition, there is increasing experi-mental evidence of tumor promotion and carcinogenesis in rodents due to the toxins This book assesses the present knowledge of toxic species of cyanobacteria and their ecology, the chemistry and toxicology of the most relevant toxins, safe con-centrations in drinking and recreational water, monitoring of organisms and toxins, mitigation of reservoir problems, and water treatment technologies Each of these areas is the subject of considerable recent research, with North America, Europe, Japan, and Australia contributing substantially This volume is intended to be useful

to environmental and public health agencies, water supply utilities, and managers

of drinking and recreational water, as well as to researchers in this field

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I would like to express my gratitude to my wife, Mary, who has supported my teaching, research, and writing throughout my career and without whose help little would have been achieved My scientific colleagues Maria Runnegar and Andrew Humpage have, over 30 years, contributed greatly to this research, from its infancy

to what is now a rapidly expanding worldwide investigation Our research collabo-rators and postgraduate students deserve recognition for their systematic contribu-tions to the field, which are evident from the coauthorship of the many papers quoted

in this volume

I would like to thank the following publishers, organizations, and individuals for permission to reproduce or modify copyrighted material used in this text: the American Chemical Society for Figures 3.2,3.3, and 10.2; Australian government for Figure 8.4; Australasian Medical Publishing Company for Figure 5.1; Peter Baker, CRC for Water Quality and Treatment, Salisbury, South Australia, for Figure 4.6; Cyanosite Image Gallery — Dr Roger Burke, University of California, River-side, and Dr Mark Schneegurt, Wichita State University — for Figure 2.3; Dr Bernard Ernst, University of Konstanz, for Figure 2.4d; Dr Larelle Fabbro for Figure 4.4; Gladstone Area Water Board for Figures 4.2 and 4.5;Journal of the Association

of Official Analytical Chemists for Figure 10.1; Royal Society of Chemisty for Figure 8.2; Taylor & Francis Journals for Figure 7.3; Wiley for Figures 2.4,6.1, and 7.1;

and the World Health Organization for Figures 4.1 and 4.3

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Table of Contents

Chapter 1 Introduction 1

References 6

Chapter 2 Toxic Cyanobacteria and Their Identification 9

2.1 The Origins of Cyanobacteria 9

2.2 Cyanobacterial Organisms 10

2.3 Classification and Nomenclature 11

2.4 Molecular Taxonomy 13

References 19

Chapter 3 Toxin Chemistry and Biosynthesis 25

3.1 Chemistry of Cylindrospermopsins 26

3.2 Synthesis of Cylindrospermopsin 28

3.3 Biosynthesis of Cylindrospermopsin 29

3.4 Chemistry of Microcystins 31

3.5 Synthesis of Microcystins 34

3.6 Biosynthesis of Microcystins: Biochemical Approaches 35

3.7 Molecular Genetic Approaches 36

References 39

Chapter 4 Cyanobacterial Ecology 45

4.1 Cyanobacteria in Freshwater 45

4.2 Light 47

4.3 Buoyancy 49

4.4 Nutrients 50

4.4.1 Phosphorus 50

4.4.2 Nitrogen 50

4.5 Distribution of Cylindrospermopsis raciborskii (Nostocales) 51

4.5.1 In Australia 52

4.6 Ecology of Cylindrospermopsis raciborskii 55

4.7 Cylindrospermopsin Production by Cylindrospermopsis raciborskii 57

4.8 Cylindrospermopsin Production by Other Cyanobacterial Species 59

4.9 Production of Other Toxins by Cylindrospermopsis raciborskii 60

4.10 Distribution of Microcystis aeruginosa 60

4.11 Distribution of Other Microcystin-Producing Species of Cyanobacteria 62

4.12 Ecology of Microcystis aeruginosa 62

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4.13 Ecology of Planktothrix Species and Anabaena flos-aquae 64

4.14 Ecology of Microcystin Production 66

4.15 Nodularia spumigena and Nodularin Production 68

References 68

Chapter 5 Cyanobacterial Poisoning of Livestock and People 77

5.1 Livestock and Wildlife Poisoning by Cyanobacterial Toxins 78

5.2 Human Poisoning by Cyanobacterial Toxins 80

5.3 Waterborne Poisoning in Brazil 80

5.4 Gastrointestinal Illness Associated with Cyanobacteria in the U.S 82

5.5 Gastroenteritis Associated with Cyanobacteria in Africa 83

5.6 Liver Damage Associated with Microcystis aeruginosa in Australia 84

5.7 Recreational Poisoning in the U.K and U.S 86

5.8 The Dialysis Tragedy in Brazil 87

5.9 Palm Island Poisoning by Cylindrospermopsin in Australia 88

5.10 Conclusions 90

References 90

Chapter 6 Cylindrospermopsin Toxicity 95

6.1 Toxicity of Cylindrospermopsin: Whole-Animal Studies 95

6.2 Oral Toxicity of Cylindrospermopsin: Studies of the No Observed Adverse Effect Level 97

6.3 Cylindrospermopsin Uptake and Excretion 98

6.4 Mechanism of Cylindrospermopsin Toxicity 99

6.5 Inhibition of Protein Synthesis 100

6.6 Cytochrome P450 in Cylindrospermopsin Toxicity 102

6.7 DNA Damage, Chromosome Damage, and Carcinogenicity 104

6.8 Micronucleus Formation in the Presence of Cylindrospermopsin 104

6.9 Whole-Animal Carcinogenicity 105

6.10 Assessment of Carcinogenicity 106

6.11 Teratogenicity, Immunotoxicity, and Reproductive Injury 106

References 106

Chapter 7 Microcystin Toxicity 109

7.1 Acute Toxicity of Microcystin to Rodents 109

7.2 Subchronic and Chronic Toxicity 110

7.3 Determination of the No Observed Adverse Effect Level for Microcystin in Mice 111

7.4 Large-Animal Toxicity 111

7.5 Determination of the No Observed Adverse Effect Level of Microcystin in Pigs 112

7.6 Toxicokinetics of Microcystin 113

7.7 Conjugation and Excretion of Microcystin 118

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7.8 Studies with Isolated Hepatocytes 119

7.9 Mechanisms of Microcystin Toxicity 121

7.10 Microcystin and Phosphatase Inhibition 121

7.11 Cytoskeletal Effects 123

7.12 Nuclear Actions of Microcystin 124

7.13 Microcystin and Apoptosis 124

7.14 Cell-Cycle Effects of Microcystin 126

7.15 Tumor Promotion by Microcystin 128

7.16 Carcinogenesis, Liver Damage, and Cancer in China 131

7.17 Microcystin, Teratogenesis, and Reproductive Toxicity 132

7.18 Conclusion 133

References 134

Chapter 8 Risk and Safety of Drinking Water: Are Cyanobacterial Toxins in Drinking Water a Health Risk? 141

8.1 Risk Assessment and Legislation 142

8.2 What Is a Risk, and How Can It Be Assessed? 145

8.3 Risk Management 146

8.4 Risk and Chemical Safety in Drinking Water — Cyanobacterial Toxins as Toxic Chemicals 146

8.5 The Tolerable Daily Intake 149

8.6 Determination of a Guideline Value for Cylindrospermopsin 150

8.7 The Tolerable Daily Intake and Drinking Water Guideline Value for Microcystin 152

8.8 Cylindrospermopsins and Microcystins as Carcinogens? 153

8.9 Cylindrospermopsin — Is It a Carcinogen? 158

8.10 Microcystins and Nodularins — Are They Carcinogens? 160

8.11 Chronic Lifetime Dose, Intermittent Acute Doses, and Recreational Exposures 161

References 163

Chapter 9 Monitoring of Reservoirs for Toxic Cyanobacteria and Analysis of Nutrients in Water 167

9.1 Monitoring Sites 168

9.2 Monitoring Frequency 169

9.3 Parameters for Monitoring — Predictive Parameters 170

9.4 Parameters for Monitoring — Identity and Number of Cyanobacterial Cells 173

9.5 Sampling 174

9.6 Cell Counting, Measurement, and Chlorophyll-a Analysis 175

9.7 Chlorophyll-a Analysis 178

9.8 Fluorescence Measurement of Cyanobacterial Concentration in Reservoirs 179

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9.9 Monitoring by Genetic Methods 180

References 180

Chapter 10 Detection and Analysis of Cylindrospermopsins and Microcystins 185

10.1 Toxin Concentration 186

10.2 In Vivo Rodent Toxicity Assays 186

10.2.1 Methods for Mouse Tests — Intact Cells 187

10.2.2 Senescent or Lysed Samples 188

10.2.3 Ethics Permission 189

10.3 Cylindrospermopsin Bioassay and Analysis 189

10.3.1 Bioassays for Cylindrospermopsin 190

10.4 Cell-Based and Cell-Free Toxicity Measurement of Cylindrospermopsin 191

10.5 ELISA of Cylindrospermopsin 192

10.6 Instrument-Based Techniques for Cylindrospermopsin 193

10.6.1 High-Performance Liquid Chromatography (HPLC) 193

10.7 Microcystins and Nodularins: Bioassay and Analysis 194

10.8 Sample Collection and Handling for Microcystins 195

10.9 Bioassays for Microcystins and Nodularins 196

10.9.1 Cell-Based Assays for Microcystins 197

10.9.2 Bacterial Luminescence Assays 197

10.10 ELISA for Microcystins and Nodularins 197

10.10.1 Polyclonal Antibodies 197

10.10.2 Monoclonal Antibodies 199

10.10.3 Phage Library Antibodies 199

10.10.4 Immunofluorimetric Assays 199

10.11 Protein Phosphatase Inhibition Assay for Microcystins and Nodularins 200

10.11.1 Methodology 200

10.12 HPLC for Microcystins and Nodularins 201

10.12.1 Advanced Instrument Techniques 202

10.13 Microcystins and Nodularins in Tissue Samples 203

10.14 Analytical Problems and Challenges 204

References 206

Chapter 11 Prevention, Mitigation, and Remediation of Cyanobacterial Blooms in Reservoirs 213

11.1 Nutrient Reduction 215

11.2 Phosphorus Reduction 216

11.2.1 Reduction to Inflow 216

11.2.2 Phosphorus Stripping 217

11.2.3 Wetlands 217

11.2.4 Low-Flow Effects 218

11.2.5 Agricultural Land 219

11.3 Catchment Management 220

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11.4 Nitrogen Reduction 221

11.5 Reservoir Remediation 222

11.6 Destratification 223

11.7 Flow 225

11.8 Phosphorus Precipitation, Sediment Capping, and Dredging 226

11.9 Algicides 227

11.9.1 Copper 227

11.9.2 Problems with the Use of Copper 227

11.9.3 Oxidants and Herbicides 229

11.10 Biological Remediation 229

11.10.1 Fish Population 230

11.10.2 Straw 231

11.10.3 Phage 231

References 231

Chapter 12 Water Treatment 237

12.1 Processes for Removing Cyanobacterial Toxins from Drinking Water Supplies 240

12.1.1 Control of Abstraction 240

12.1.2 Bank Filtration 241

12.2 Water Filtration, Coagulation, and Clarification 242

12.3 Activated Carbon 245

12.3.1 Biological Activated Carbon 246

12.3.2 Powdered Activated Carbon 247

12.4 Ozonation and Chlorination 248

12.4.1 Chlorine 250

12.5 Titanium Dioxide Photocatalysis 250

12.6 Slow Sand Filtration 251

12.7 Membrane Filtration 252

12.8 Conclusions 253

References 254

Chapter 13 Emerging Issues 259

13.1 Ecological Issues 259

13.2 Health Issues 261

13.3 Water Treatment 262

References 263

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In many parts of the world, surface waters are used for the drinking water supply The quality of these surface waters is very variable both within and between countries In developed countries, this water is treated through purification pro-cesses; in less developed areas, many people have to rely on untreated water Toxic cyanobacteria are a normal part of the phytoplankton of surface waters and therefore can present a hazard to consumers if they are present in sufficient numbers The toxins from cyanobacteria are resistant to boiling and can also pass through con-ventional water treatment plants The understanding of cyanobacteria and their toxins and measures for the control of both has expanded greatly in recent years This volume aims to provide a current account of present knowledge of the two potentially most damaging cyanobacterial toxins in drinking water: cylindrosperm-opsin and microcystin

Cyanobacteria are generally distributed in the biosphere, with many species in freshwaters (Whitton and Potts 2000) In clean (oligotrophic — few nutrients) lakes and rivers, their cell concentration is low and there is a range of species at any given time The size of the cyanobacterial population under these circumstances will be limited by lack of nutrients, particularly available phosphate The organisms are photosynthetic and capable of growth under low light intensities, so that they can

be found at depth in the water of clear lakes Some species have specialized nitrogen-fixing cells, called heterocysts, that allow them to grow when very little inorganic nitrogen is available in the water These cells provide a morphological feature that assists in their identification (Chapter 2) As nutrient availability in lakes and rivers increases through human activity, whether from intensification of agriculture or human waste disposal, the size of the cyanobacterial population rises The final condition of freshwater is termed eutrophic (good nutrients) when the nutrients are sufficient to support high populations of phytoplankton

These eutrophic waters may have dominant green algae or diatoms, or they may

be seasonally subject to water blooms of cyanobacteria The circumstances of cyano-bacterial dominance are discussed in Chapter 4 and occur relatively frequently in reservoirs and weir pools in slow-flowing rivers One of the factors that may con-tribute to a single species of cyanobacterium becoming the dominant organism in a water body is the ability to produce toxins Phytoplankton, including cyanobacteria, are the primary food source for a diversity of consuming organisms in freshwater The presence of toxins in particular species of cyanobacteria may provide a com-petitive advantage by suppressing consumption, allowing the toxic organisms to outgrow nontoxic phytoplankton

The cyanobacterial toxins include a range of chemical compounds, with those currently identified being predominantly alkaloids and peptides (Chapter 3) The

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