Toxicology and risk assessment of freshwater cyanobacterial (blue-green algal) toxins in water.

The occurrence of cyanobacterial toxins affects aquatic organisms, terrestrial animals (both wild and domestic), and humans. Detrimental effects have been documented in the scientific literature during the past 50 years. Possible guideline values of some cyanobacterial toxins (microcystins, cylindrospermopsin, and anatoxin-a) are estimated, and they show that children and infants are more susceptible to cyanobacterial toxins than adults. Therefore, particular attention should be paid when cyanobacterial blooms occur, even at relatively low cell counts, to protect children and infants from possible risks. Based on these guideline values and the occurrence of the toxins, it can be concluded that chronic and subchronic exposure to cyanobacterial toxins does occur in some populations, particularly in developing countries where high proportions of the population consume untreated surface water directly, such as pond, ditch, river, or reservoir water. Because wildlife and domestic animals consume a large amount of untreated water daily, they are at higher risk than humans from cyanobacterial toxins. Calculated guideline values in Section X show that a relatively high risk posed by the toxins to these animals is likely to occur, even at low cell densities.

[1]  Toshinori Yoshida,et al.  Acute oral toxicity of microcystin-LR, a cyanobacterial hepatotoxin, in mice. , 1998, Natural toxins.

[2]  Philip R. Cohen,et al.  Cyanobacterial microcystin‐LR is a potent and specific inhibitor of protein phosphatases 1 and 2A from both mammals and higher plants , 1990, FEBS letters.

[3]  F. F. Davidson Poisoning of Wild and Domestic Animals by a Toxic Waterbloom of Nostoc rivulare Kuetz , 1959 .

[4]  W. Carmichael,et al.  The Mosaic Nature of Toxic Blooms of Cyanobacteria , 1981 .

[5]  I. Falconer,et al.  Clinical and Pathological Changes in Sheep Experimentally Poisoned by the Blue-Green Alga Microcystis aeruginosa , 1984, Veterinary pathology.

[6]  J. Eriksson,et al.  Hepatocellular uptake of 3H-dihydromicrocystin-LR, a cyclic peptide toxin. , 1990, Biochimica et biophysica acta.

[7]  K. Sivonen Effects of light, temperature, nitrate, orthophosphate, and bacteria on growth of and hepatotoxin production by Oscillatoria agardhii strains , 1990, Applied and environmental microbiology.

[8]  John McNeill,et al.  International Code of Botanical Nomenclature , 1983 .

[9]  N. Lagos,et al.  Inhibitory effects of Microcystis aeruginosa toxin on ion pumps of the gill of freshwater fish. , 1994, Toxicon : official journal of the International Society on Toxinology.

[10]  J. Zwiller,et al.  Characterization of microcystin-LR, a potent inhibitor of type 1 and type 2A protein phosphatases. , 1990, The Journal of biological chemistry.

[11]  Comparison of the solution structures of microcystin-LR and motuporin , 1995, Nature Structural Biology.

[12]  I. Falconer,et al.  Tumour promotion by Microcystis sp., a blue‐green alga occurring in water supplies , 1989, The Medical journal of Australia.

[13]  J. Gallon,et al.  Biosynthesis of the tropane-related cyanobacterial toxin anatoxin-a: role of ornithine decarboxylase. , 1990, Phytochemistry.

[14]  Richard E. Moore,et al.  Cylindrospermopsin: a potent hepatotoxin from the blue-green alga Cylindrospermopsis raciborskii , 1992 .

[15]  D. Hartshorne,et al.  Hepatocyte deformation induced by cyanobacterial toxins reflects inhibition of protein phosphatases. , 1990, Biochemical and biophysical research communications.

[16]  D. Steffensen,et al.  Paralytic shellfish poisons from Australian cyanobacterial blooms , 1994 .

[17]  Dudley H. Williams,et al.  The structure of cyanoginosin-LA, a cyclic heptapeptide toxin from the cyanobacterium Microcystis aeruginosa , 1985 .

[18]  J. Gentile,et al.  Toxins of a Blue-Green Alga: Similarity to Saxitoxin , 1968, Science.

[19]  D. Cardo,et al.  Liver failure and death after exposure to microcystins at a hemodialysis center in Brazil. , 1998, The New England journal of medicine.

[20]  K. Sivonen,et al.  The effect of water treatment processes on the removal of hepatotoxins fromMicrocystis andOscillatoria cyanobacteria: A laboratory study , 1989 .

[21]  E. Prepas,et al.  Toxin Release from Microcystis Aeruginosa after Chemical Treatment , 1993 .

[22]  R. Smith,et al.  A rapid analysis of water for anatoxin a, the unstable toxic alkaloid from Anabaena flos-aquae, the stable non-toxic alkaloids left after bioreduction and a related amine which may be nature's precursor to anatoxin a. , 1987, Veterinary and human toxicology.

[23]  J. Hayman,et al.  Beyond the Barcoo — probable human tropical cyanobacterial poisoning in outback Australia , 1992, The Medical journal of Australia.

[24]  J. J. Sasner,et al.  Demonstration of a toxin from Aphanizomenon flos-aquae (L.) Ralfs. , 1968, Canadian journal of microbiology.

[25]  D. Williams,et al.  Chemical and biological evidence links microcystins to salmon 'netpen liver disease'. , 1993, Toxicon : official journal of the International Society on Toxinology.

[26]  F. Zambrano,et al.  Effects of microcystin-LR on the partial reactions of the Na(+)-K+ pump of the gill of carp (Cyprinus carpio Linneo). , 1996, Toxicon : official journal of the International Society on Toxinology.

[27]  C. Huber The crystal structure and absolute configuration of 2,9‐diacetyl‐9‐azabicyclo[4,2,1]non‐2,3‐ene , 1972 .

[28]  D. Slatkin,et al.  Toxins of Microcystis aeruginosa and their hematological and histopathological effects , 1984 .

[29]  M. Watanabe,et al.  Electron microscopic studies on experimental poisoning in mice induced by cylindrospermopsin isolated from blue-green alga Umezakia natans. , 1994, Toxicon : official journal of the International Society on Toxinology.

[30]  Michael D. Burch,et al.  Destruction of cyanobacterial peptide hepatotoxins by chlorine and chloramine , 1994 .

[31]  Isolated rat liver perfusion studies with cyclic heptapeptide toxins of Microcystis and Oscillatoria (freshwater cyanobacteria). , 1988, Toxicon : official journal of the International Society on Toxinology.

[32]  W. Carmichael,et al.  Blue-green algae (Microcystis aeruginosa) hepatotoxicosis in dairy cows. , 1987, American journal of veterinary research.

[33]  I. Falconer,et al.  Toxicity of the cyanobacterium Nodularia spumigena Mertens. , 1988, Toxicon : official journal of the International Society on Toxinology.

[34]  A. Humpage,et al.  Isolation and toxicity of Cylindrospermopsis raciborskii from an ornamental lake. , 1997, Toxicon : official journal of the International Society on Toxinology.

[35]  R. Harrison,et al.  Agricultural chemicals and the environment , 1996 .

[36]  J. Yates,et al.  Structural characterization of toxic cyclic peptides from blue-green algae by tandem mass spectrometry. , 1989, Proceedings of the National Academy of Sciences of the United States of America.

[37]  E. Prepas,et al.  Sources of Uncertainty in Assessing the Health Risk of Cyanobacterial Blooms in Drinking Water Supplies , 1994 .

[38]  P. Turner,et al.  Pneumonia associated with contact with cyanobacteria. , 1990, BMJ.

[39]  R. Andersen,et al.  Molecular mechanisms underlying he interaction of motuporin and microcystins with type-1 and type-2A protein phosphatases. , 1996, Biochemistry and cell biology = Biochimie et biologie cellulaire.

[40]  G. Codd,et al.  Eutrophication and toxic cyanobacteria in freshwaters , 1985 .

[41]  J. V. Smith,et al.  Oral toxicity of a bloom of the Cyanobacterium microcystis Aeruginosa administered to mice over periods up to 1 year. , 1988, Journal of toxicology and environmental health.

[42]  W. Carmichael,et al.  Algal toxins and water‐based diseases , 1985 .

[43]  I. Falconer,et al.  Persistence of cyclic peptide toxins in dried Microcystis aeruginosa crusts from lake Mokoan, Australia , 1995 .

[44]  J. Eriksson,et al.  Synthesis, organotropism and hepatocellular uptake of two tritium-labeled epimers of dihydromicrocystin-LR, a cyanobacterial peptide toxin analog. , 1990, Toxicon : official journal of the International Society on Toxinology.

[45]  K. Sivonen,et al.  Preliminary characterization of neurotoxic cyanobacteria blooms and strains from Finland , 1989 .

[46]  D. Bourne,et al.  Enzymatic pathway for the bacterial degradation of the cyanobacterial cyclic peptide toxin microcystin LR , 1996, Applied and environmental microbiology.

[47]  S. Hrudey,et al.  Quantitation of the microcystin hepatotoxins in water at environmentally relevant concentrations with the protein phosphatase bioassay. , 1994, Environmental science & technology.

[48]  Dudley H. Williams,et al.  Structural studies on cyanoginosins-LR, -YR, -YA, and -YM, peptide toxins from Microcystis aeruginosa , 1985 .

[49]  J. Eriksson,et al.  Rapid analysis of peptide toxins in cyanobacteria. , 1988, Journal of chromatography.

[50]  M. Lukač,et al.  Influence of trace metals on growth and toxin production of Microcystis aeruginosa. , 1993, Toxicon : official journal of the International Society on Toxinology.

[51]  H. Benson Microbiological Applications: A Laboratory Manual in General Microbiology , 1985 .

[52]  K. Sivonen,et al.  Removal of cyanobacterial toxins in water treatment processes: Laboratory and pilot‐scale experiments , 1988 .

[53]  J. Dellinger,et al.  Comparison of effects of anatoxin-a(s) and paraoxon, physostigmine and pyridostigmine on mouse brain cholinesterase activity. , 1988, Toxicon : official journal of the International Society on Toxinology.

[54]  W. Carmichael,et al.  Pharmacology of anatoxin-a, produced by the freshwater cyanophyte Anabaena flos-aquae NRC-44-1. , 1979, Toxicon : official journal of the International Society on Toxinology.

[55]  R. Harrison,et al.  Detection analysis and risk assessment of cyanobacterial toxins , 1996 .

[56]  S. Blackburn,et al.  EFFECT OF CULTURE AND BLOOM DEVELOPMENT AND OF SAMPLE STORAGE ON PARALYTIC SHELLFISH POISONS IN THE CYANOBACTERIUM ANABAENA CIRCINALIS , 1997 .

[57]  W. Carmichael,et al.  In vitro and in vivo effects of protein phosphatase inhibitors, microcystins and nodularin, on mouse skin and fibroblasts. , 1990, Biochemical and biophysical research communications.

[58]  E. S. Tisdale,et al.  The 1930-1931 Drought and Its Effect Upon Public Water Supply. , 1931, American journal of public health and the nation's health.

[59]  D. Botes,et al.  Isolation and characterization of four toxins from the blue-green alga, Microcystis aeruginosa. , 1982, Toxicon : official journal of the International Society on Toxinology.

[60]  H. Fujiki,et al.  Structure‐Function Relationships of Microcystins, Liver Tumor Promoters, in Interaction with Protein Phosphatase , 1991, Japanese journal of cancer research : Gann.

[61]  W. Carmichael,et al.  Blood pressure and hepatocellular effects of the cyclic heptapeptide toxin produced by the freshwater cyanobacterium (blue-green alga) Microcystis aeruginosa strain PCC-7820. , 1988, Toxicon : official journal of the International Society on Toxinology.

[62]  J. Baeyens Interactions between calcium channel blockers and non-cardiovascular drugs: interactions with anticancer drugs. , 1988, Pharmacology & toxicology.

[63]  Wayne W. Carmichael,et al.  Diseases related to freshwater blue-green algal toxins, and control measures , 1993 .

[64]  W. Carmichael,et al.  Uptake and subcellular localization of tritiated dihydro-microcystin-LR in rat liver. , 1991, Toxicon : official journal of the International Society on Toxinology.

[65]  K. Sivonen,et al.  Isolation and identification of eight microcystins from thirteen Oscillatoria agardhii strains and structure of a new microcystin , 1993, Applied and environmental microbiology.

[66]  S. Oishi,et al.  Effects of Environmental Factors on Toxicity of a Cyanobacterium (Microcystis aeruginosa) under Culture Conditions , 1985, Applied and environmental microbiology.

[67]  L. Lawton,et al.  Cyanobacterial (Blue‐Green Algal) Toxins and their Significance in UK and European Waters , 1991 .

[68]  R. Sakai,et al.  Structures of three new cyclic heptapeptide hepatotoxins produced by the cyanobacterium (blue-green alga) nostoc sp. strain 1521 , 1990 .

[69]  S. Hooser,et al.  Algae intoxication in livestock and waterfowl. , 1989, The Veterinary clinics of North America. Food animal practice.

[70]  K. Jann Structure and biosynthesis of O-antigens. , 1984 .

[71]  Ian R. Falconer,et al.  Algal toxins in seafood and drinking water , 1993 .

[72]  I. Falconer,et al.  The occurrence and consequences of blooms of the toxic blue-green alga Microcystis aeruginosa in Eastern Australia , 1983 .

[73]  C. Luke,et al.  Illness associated with blue‐green algae , 1992, The Medical journal of Australia.

[74]  H. Rapoport,et al.  Synthetic and conformational studies on anatoxin-a: a potent acetylcholine agonist. , 1985, Journal of medicinal chemistry.

[75]  G. Codd Cyanobacterial toxins: Occurrence, properties and biological significance , 1995 .

[76]  I. Falconer,et al.  Severe hepatotoxicity caused by the tropical cyanobacterium (blue-green alga) Cylindrospermopsis raciborskii (Woloszynska) Seenaya and Subba Raju isolated from a domestic water supply reservoir , 1985, Applied and environmental microbiology.

[77]  I. Vila,et al.  Toxicity of a soluble peptide from Microcystis sp. to zooplankton and fish , 1990 .

[78]  Peter Bradshaw,et al.  Using activated carbon to remove toxicity from drinking water containing cyanobacterial blooms , 1989 .

[79]  M. Watanabe,et al.  Isolation of cylindrospermopsin from a cyanobacterium Umezakia natans and its screening method. , 1994, Toxicon : official journal of the International Society on Toxinology.

[80]  K. Beattie,et al.  Toxicity and extrachromosomal DNA in strains of the cyanobacterium Microcystis aeruginosa , 1985 .

[81]  D. Williams,et al.  Tissue distribution and clearance of tritium-labeled dihydromicrocystin-LR epimers administered to Atlantic salmon via intraperitoneal injection. , 1995, Toxicon : official journal of the International Society on Toxinology.

[82]  I. Falconer,et al.  Biological half-life, organ distribution and excretion of 125-I-labelled toxic peptide from the blue-green alga Microcystis aeruginosa. , 1986, Australian journal of biological sciences.

[83]  I. Falconer,et al.  Cytoskeletal changes in hepatocytes induced by Microcystis toxins and their relation to hyperphosphorylation of cell proteins. , 1992, Chemico-biological interactions.

[84]  W. Carmichael,et al.  CHAPTER 9 – Taxonomy of Toxic Cyanophyceae (Cyanobacteria) , 1993 .

[85]  D. Stevens,et al.  Stability studies on the cyanobacterial nicotinic alkaloid anatoxin-A. , 1991, Toxicon : official journal of the International Society on Toxinology.

[86]  W. Carmichael,et al.  Natural toxins from cyanobacteria (blue-green Algae) , 1990 .

[87]  I. Falconer Measurement of Toxins from Blue-green Algae in Water and Foodstuffs , 1993 .

[88]  H. Dillenberg,et al.  Toxic waterbloom in Saskatchewan, 1959. , 1960, Canadian Medical Association journal.

[89]  W. Carmichael,et al.  A model system for studying the bioavailability of intestinally administered microcystin-LR, a hepatotoxic peptide from the cyanobacterium Microcystis aeruginosa. , 1989, Pharmacology & toxicology.

[90]  J. Cockburn,et al.  The acceptability of personal invitations to a mammographic screening program , 1993, The Medical journal of Australia.

[91]  R. Wedepohl,et al.  Cyanobacteria (blue-green algae) in wisconsin waters: acute and chronic toxicity , 1990 .

[92]  E. Prepas,et al.  Biotransformation of the Cyanobacterial Hepatotoxin Microcystin-LR, as Determined by HPLC and Protein Phosphatase Bioassay. , 1995, Environmental science & technology.

[93]  J. Eriksson,et al.  Histopathological effects of microcystin-LR, a cyclic peptide toxin from the cyanobacterium (blue-green alga) Microcystis aeruginosa on common carp (Cyprinus carpio L.) , 1991 .

[94]  M. V. Veldee An Epidemiological Study of Suspected Water-borne Gastroenteritis. , 1931, American journal of public health and the nation's health.

[95]  N. R. Hunter,et al.  Anatoxin-a, a toxic alkaloid from Anabaena flos-aquae NRC-44h , 1977 .

[96]  P. Gorham,et al.  Isolation and identification of the fast-death factor in Microcystis aeruginosa NRC-1. , 1959, Canadian journal of biochemistry and physiology.

[97]  E. ArévaloJiménez,et al.  Primary liver cancer , 1985 .

[98]  Y. Ueno,et al.  Detection of microcystins, a blue-green algal hepatotoxin, in drinking water sampled in Haimen and Fusui, endemic areas of primary liver cancer in China, by highly sensitive immunoassay. , 1996, Carcinogenesis.

[99]  I. Falconer,et al.  Liver Pathology in Mice in Poisoning by the Blue-Green Alga Microcystis Aeruginosa , 1981 .

[100]  G. A. Miura,et al.  Characterization of chemically tritiated microcystin-LR and its distribution in mice. , 1989, Toxicon : official journal of the International Society on Toxinology.

[101]  J. Eloff,et al.  Effect of Culture Age and pH of Culture Medium on the Growth and Toxicity of the Blue-green Alga Microcystis aeruginosa , 1983 .

[102]  W. Carmichael,et al.  Detection of an anatoxin-a(s)-like anticholinesterase in natural blooms and cultures of cyanobacteria/blue-green algae from Danish lakes and in the stomach contents of poisoned birds. , 1997, Toxicon : official journal of the International Society on Toxinology.

[103]  W. Carmichael,et al.  Cyanobacteria secondary metabolites--the cyanotoxins. , 1992, The Journal of applied bacteriology.

[104]  N. Takamura,et al.  FATE OF THE TOXIC CYCLIC HEPTAPEPTIDES, THE MICROCYSTINS, FROM BLOOMS OF MICROCYSTIS (CYANOBACTERIA) IN A HYPERTROPHIC LAKE 1 , 1992 .

[105]  W. Carmichael,et al.  Toxins from Freshwater Cyanobacteria , 1984 .

[106]  B. Zilberg Gastroenteritis in Salisbury. European children--a five-year study. , 1966, The Central African journal of medicine.

[107]  M. Burch,et al.  Toxicity of the blue-green alga (cyanobacterium) Microcystis aeruginosa in drinking water to growing pigs, as an animal model for human injury and risk assessment , 1994 .

[108]  Shun-zhang Yu Primary prevention of hepatocellular carcinoma , 1995, Journal of gastroenterology and hepatology.

[109]  W. Carmichael,et al.  Paralytic shellfish poisons produced by the freshwater cyanobacterium Aphanizomenon flos-aquae NH-5. , 1986, Toxicon : official journal of the International Society on Toxinology.

[110]  E. Prepas,et al.  Hepatic and renal pathology of intraperitoneally administered microcystin-LR in rainbow trout (Oncorhynchus mykiss). , 1996, Toxicon : official journal of the International Society on Toxinology.

[111]  G. Codd,et al.  Toxic blooms of cyanobacteria in Lake Alexandrina, South Australia — Learning from history , 1994 .

[112]  E. Albuquerque,et al.  Anatoxin-a: a novel, potent agonist at the nicotinic receptor. , 1980, Molecular pharmacology.

[113]  I. Falconer CHAPTER 11 – Mechanism of Toxicity of Cyclic Peptide Toxins from Blue-green Algae , 1993 .

[114]  K. Rinehart,et al.  Nodularin, microcystin, and the configuration of Adda , 1988 .

[115]  David G. Mann,et al.  Algae: An Introduction to Phycology , 1996 .

[116]  Alastair C. Wardlaw,et al.  Practical Statistics for Experimental Biologists , 1985 .

[117]  W. Carmichael,et al.  Isolation and characterization of hepatotoxic microcystin homologs from the filamentous freshwater cyanobacterium Nostoc sp. strain 152 , 1990, Applied and environmental microbiology.

[118]  P. Henriksen,et al.  Confirmation of anatoxin-a(s), in the cyanobacterium Anabaena lemmermannii, as the cause of bird kills in Danish lakes. , 1997, Toxicon : official journal of the International Society on Toxinology.

[119]  I. Falconer Health Problems from Exposure to Cyanobacteria and Proposed Safety Guidelines for Drinking and Recreational Water , 1994 .

[120]  S. Suzuki,et al.  Stability of microcystins from cyanobacteria--II. Effect of UV light on decomposition and isomerization. , 1995, Toxicon : official journal of the International Society on Toxinology.

[121]  D. Bleyl,et al.  IARC Monographs on the Evaluation of Carcinogenic Risks to Humans. Overall Evaluations of Carcinogenicity: An Updating of IARC Monographs vol. 1 to 42. Supplement 7. 440 Seiten. International Agency for Research on Cancer, Lyon 1987. Preis: 65, – s.Fr , 1989 .

[122]  A. N. Rai Handbook of symbiotic cyanobacteria. , 1990 .

[123]  C. Scrimgeour,et al.  Identification of anatoxin-A in benthic cyanobacteria (blue-green algae) and in associated dog poisonings at Loch Insh, Scotland. , 1992, Toxicon : official journal of the International Society on Toxinology.

[124]  J. Eloff,et al.  Toxicological Studies on Microcystis , 1981 .

[125]  N. G. Carr,et al.  The Biology of Cyanobacteria , 1982 .

[126]  W. Carmichael The toxins of cyanobacteria. , 1994, Scientific American.

[127]  C. Keevil,et al.  Routes of Intoxication , 1994 .

[128]  P. Orr,et al.  Release and degradation of microcystin following algicide treatment of a Microcystis aeruginosa bloom in a recreational lake, as determined by HPLC and protein phosphatase inhibition assay , 1994 .

[129]  I. Falconer,et al.  Toxin production by Microcystis aeruginosa cultures , 1983 .

[130]  R. Andersen,et al.  Identification of protein phosphatase inhibitors of the microcystin class in the marine environment. , 1993, Toxicon : official journal of the International Society on Toxinology.

[131]  R. Zurawell,et al.  Microcystin-LR concentration in aquatic food web compartments from lakes of varying trophic status , 1996 .

[132]  R. Wilkins,et al.  Toxicity of microcystin-LR, isolated from Microcystis aeruginosa, against various insect species. , 1995, Toxicon : official journal of the International Society on Toxinology.

[133]  Richard E. Moore,et al.  Investigations of a neurotoxic oscillatorialean strain (Cyanophyceae) and its toxin. Isolation and characterization of homoanatoxin‐a , 1992 .

[134]  Richard E. Moore,et al.  Anatoxin-a(s), a potent anticholinesterase from Anabaena flos-aquae , 1989 .

[135]  E. Prepas,et al.  Accumulation and elimination of cyanobacterial hepatotoxins by the freshwater clam Anodonta grandis simpsoniana , 1997 .

[136]  Edwin C. Lippy,et al.  Gastrointestinal Illness at Sewickley, Pa. , 1976 .

[137]  G. Shaw,et al.  Blooms of the cylindrospermopsin containing cyanobacterium, Aphanizomenon ovalisporum (Forti), in newly constructed lakes, Queensland, Australia , 1999 .

[138]  L. Sirenko,et al.  Some Aspects Concerning Remote After-Effects of Blue-Green Algae Toxin Impact on Warm-Blooded Animals , 1981 .

[139]  K. Sivonen,et al.  Persistence of cyanobacterial hepatotoxin, microcystin-LR in particulate material and dissolved in lake water , 1997 .

[140]  Temporal Association Between an Algal Bloom and Mutagenicity in a Water Reservoir , 1981 .

[141]  I. Falconer,et al.  Isolation, Characterization and Pathology of the Toxin from the Blue-Green Alga Microcystis Aeruginosa , 1981 .

[142]  R. Aronstam,et al.  Anatoxin-a interactions with cholinergic synaptic molecules. , 1981, Proceedings of the National Academy of Sciences of the United States of America.

[143]  M. Shirai,et al.  Isolation of two toxic heptapeptide microcystins from an axenic strain of Microcystis aeruginosa, K-139. , 1991, Toxicon : official journal of the International Society on Toxinology.

[144]  J. Fohlmeister,et al.  Sodium channels blocked by aphantoxin obtained from the blue-green alga, Aphanizomenon flos-aquae. , 1982, Toxicon : official journal of the International Society on Toxinology.

[145]  S. Byth,et al.  PALM ISLAND MYSTERY DISEASE , 1980, The Medical journal of Australia.

[146]  W. Carmichael,et al.  Anatoxin-a(s), an anticholinesterase from the cyanobacterium Anabaena flos-aquae NRC-525-17. , 1987, Toxicon : official journal of the International Society on Toxinology.

[147]  D. F. Jackson Algae and Man , 1965, Springer US.

[148]  Wayne W. Carmichael,et al.  The Water Environment , 1981 .

[149]  J. Sýkora,et al.  Cyanobacteria and Endotoxins in Drinking Water Supplies , 1981 .

[150]  M. Kent Netpen liver disease (NLD) of salmonid fishes reared in sea water: species susceptibility, recovery, and probable cause. , 1990 .

[151]  J. Eriksson,et al.  Structure and toxicity of a peptide hepatotoxin from the cyanobacterium Oscillatoria agardhii. , 1989, Toxicon : official journal of the International Society on Toxinology.

[152]  J. Raven,et al.  Algae and Human Affairs. , 1989 .

[153]  W. Carmichael,et al.  Structures of three new homotyrosine-containing microcystins and a new homophenylalanine variant from Anabaena sp. strain 66. , 1992, Chemical research in toxicology.

[154]  K. Sivonen,et al.  Biodegradability and adsorption on lake sediments of cyanobacterial hepatotoxins and anatoxin‐a , 1994, Letters in applied microbiology.

[155]  K. Sivonen,et al.  Production and biodegradation of cyanobacterial toxins - a laboratory study , 1991, Archiv für Hydrobiologie.

[156]  D. Hilbelink,et al.  Evaluation of the subacute toxicity and teratogenicity of anatoxin-a. , 1980, Toxicon : official journal of the International Society on Toxinology.

[157]  Ø. Østensvik,et al.  Toxicity Studies with Blue-Green Algae from Norwegian Inland Waters , 1981 .

[158]  M. Kent,et al.  Suspected toxicopathic hepatic necrosis and megalocytosis in pen-reared Atlantic salmon Salmo salar in Puget Sound, Washington, USA. , 1988 .

[159]  P. G. Thiel,et al.  Liquid chromatographic determination of the cyanoginosins, toxins produced by the cyanobacterium Microcystis aeruginosa. , 1987, Journal of chromatography.

[160]  J. Fawell,et al.  Production, detection, and quantification of cyanobacterial toxins , 1989 .

[161]  I. Falconer,et al.  Effect of toxin from the cyanobacterium Microcystis aeruginosa on ultrastructural morphology and actin polymerization in isolated hepatocytes. , 1986, Toxicon : official journal of the International Society on Toxinology.

[162]  J. Gallon,et al.  Biochemistry of the algae and cyanobacteria , 1988 .

[163]  A. Dabholkar,et al.  Ultrastructural changes in the mouse liver induced by hepatotoxin from the freshwater cyanobacterium Microcystis aeruginosa strain 7820. , 1987, Toxicon : official journal of the International Society on Toxinology.

[164]  W. Carmichael,et al.  Structural modifications imparting reduced toxicity in microcystins from Microcystis spp. , 1993, Toxicon : official journal of the International Society on Toxinology.

[165]  I. Falconer Tumor promotion and liver injury caused by oral consumption of cyanobacteria , 1991 .

[166]  V. Vasconcelos Uptake and depuration of the heptapeptide toxin microcystin-LR in Mytilus galloprovincialis , 1995 .

[167]  E. Rietschel Chemistry Of Endotoxin , 1985 .

[168]  G. Codd,et al.  Cyanobacterial toxins: occurrence, modes of action, health effects and exposure routes. , 1997, Archives of toxicology. Supplement. = Archiv fur Toxikologie. Supplement.

[169]  A. Bourke,et al.  An outbreak of hepato-enteritis (the Palm Island mystery disease) possibly caused by algal intoxication , 1983 .

[170]  I. Falconer,et al.  Effect of the cyanobacterial (blue-green algal) toxins from Microcystis aeruginosa on isolated enterocytes from the chicken small intestine. , 1992, Toxicon : official journal of the International Society on Toxinology.