Human Exposure to Cyanotoxins and their Effects on Health

Open access

Cyanotoxins are secondary metabolites produced by cyanobacteria. They pose a threat to human health and the environment. This review summarises the existing data on human exposure to cyanotoxins through drinking water, recreational activities (e.g., swimming, canoeing or bathing), the aquatic food web, terrestrial plants, food supplements, and haemodialysis. Furthermore, it discusses the tolerable daily intake and guideline values for cyanotoxins (especially microcystins) as well as the need to implement risk management measures via national and international legislation.

1. Chorus I, Bartram J. Toxic Cyanobacteria in Water: A Guide to Their Public Health Consequences, Monitoring, and Management. London: E&FN Spon; 1999.

2. Chorus I. Cyanotoxins - Occurrence, Causes, Consequences. Berlin: Springer-Verlag; 2001.

3. Kaebernick M, Neilan BA. Ecological and molecular investigations of cyanotoxin production. FEMS Microbiol Ecol 2001;35:1-9.

4. Briand JF, Jacket S, Bernard C, Humbert JF. Health hazards for terrestrial vertebrates from toxic cyanobacteria in surface water ecosystems. Vet Res 2003;34:361-77. doi: 10.1051/ vetres:2003019

5. Fitzgerald JD. Cyanotoxins and human health - overview. In: Chorus I, editor. Cyanotoxins: occurrence, causes, consequences. Berlin: Springer-Verlag; 2001. p. 179-90.

6. Carmichael WW, Falconer IR. Diseases related to freshwater blue-green algal toxins, and control measures. In: Falconer IR, editor. Algal toxins in seafood and drinking water. London: Academic Press; 1993. p. 187-209.

7. Falconer IR. Algal toxins and human health. In: Hrubec J, editor. Handbook of environmental chemistry. Vol. 5, part C. Berlin: Springer-Verlag; 1998. p. 53-82.

8. Kuiper-Goodman T, Falconer IR, Fitzgerald J. Human health aspects. In: Chorus I, Bartram J, editors. Toxic cyanobacteria in water. A guide to their public health consequences, monitoring and management. London: E&FN Spon; 1999. p. 113-53.

9. Svirčev Z, Krstić S, Miladinov-Mikov M, Baltić V, Vidović M. Freshwater cyanobacterial blooms and primary liver cancer epidemiological studies in Serbia. J Environ Sci Health C Environ Carcinog Ecotoxicol Rev 2009;27:36-55. doi: 10.1080/10590500802668016

10. Jochimsen EM, Carmichael WW, An JS, Cardo DM, Cookson ST, Holmes CE, Antunes MB, de Melo Filho DA, Lyra TM, Barreto VS, Azevedo SM, Jarvis WR. Liver failure and death after exposure to microcystins at a hemodialysis center in Brazil. N Engl J Med 1998;338:873-8.

11. Zhou L, Yu H, Chen K. Relationship between microcystin in drinking water and colorectal cancer. Biomed Environ Sci 2002;15:166-71.

12. Maatouk I, Bouaicha N, Plessis MJ, Perin F. Detection by 32P-postlabeling detection of 8-oxo-7, 8-dihydro-20- deoxyguanosine in DNA as biomarker of microcystin-LR and nodularin-induced DNA damages in vitro in primary cultured rat hepatocytes and in vivo in rat liver. Mutat Res 2004;564:9-20.

13. International Agency for Research on Cancer (IARC). Carcinogenicity of nitrate, nitrite, and cyanobacterial peptide toxins. Lancet Oncol 2006;7:628-9. doi: 10.1016/S1470-2045(06)70789-6

14. World Health Organization (WHO). Guidelines for drinkingwater quality. 2nd ed. Addendum to Vol. 2. Geneva: WHO; 1998.

15. Dietrich D, Hoeger S. Guidance values for microcystins in water and cyanobacterial supplement products (blue-green algal supplements): a reasonable or misguided approach? Toxicol Appl Pharmacol 2005;203:273-89.

16. Burch MD. Effective doses, guidelines and regulations. Adv Exp Med Biol 2008;619:831-53. doi: 10.1007/978-0-387-75865-7_36

17. Westrick JA. Everything a manager should know about algal toxins but was afraid to ask. JAWWA 2003;95:26-34.

18. Hoeger SJ, Shaw G, Hitzfeld BC, Dietrich DR. Occurrence and elimination of cyanobacterial toxins in two Australian drinking water treatment plants. Toxicon 2004;43:639-49. doi: 10.1016/j.toxicon.2004.02.019

19. Hoeger SJ, Hitzfeld BC, Dietrich DR. Occurrence and elimination of cyanobacterial toxins in drinking water treatment plants. Toxicol Appl Pharmacol 2005;203:231-42.

20. Svirčev Z, Baltić V, Gantar M, Juković M, Stojanović D, Baltić M. Molecular Aspects of microcystin-induced hepatotoxicity and hepatocarcinogenesis. J Environ Sci Health C Environ Carcinog Ecotoxicol Rev 2010;28:39-59. doi: 10.1080/10590500903585382

21. Drobac D, Svirčev Z, Tokodi N, Vidović M, Baltić V, Božić- Krstić V, Lazić D, Pavlica T. Microcystins - potential risk factors in carcinogenesis of primary liver cancer in Serbia. Geographica Pannonica 2011;15:70-80.

22. Svirčev Z, Simeunović J, Subakov-Simić G, Krstić S, Vidović M. Freshwater cyanobacterial blooms and cyanotoxin production in Serbia in the past 25 years. Geographica Pannonica 2007;11:12-21.

23. Fleming L, Rivero C, Burns J, Williams C, Beana J, Shea K, Stinn J. Bluegreen algal (cyanobacterial) toxins, surface drinking water, and liver cancer in Florida. Harmful Algae 2002;1:157-68.

24. Yu SZ. Primary prevention of hepatocellular carcinoma. J Gastroenterol Hepatol 1995;10:674-82.

25. Grauer FH, Arnold HL. Seaweed dermatitis: first report of dermatitis-producing marine algae. Arch Dermatol 1961;84:720-32.doi:10.1001/archderm.1961.01580170014003

26. Cardellina JH 2nd, Marner FJ, Moore RE. Seaweed dermatitis: structure of lyngbyatoxin A. Science 1979;204:193-5. doi: 10.1126/science.107586

27. Yasumoto T, Murata M. Marine toxins. Chem Rev 1993;93:1897-909.

28. Stewart I, Webb PM, Schluter PJ, Shaw GR. Recreational and occupational field exposure to freshwater cyanobacteria - a review of anecdotal and case reports, epidemiological studies and the challenges for epidemiologic assessment. Environ Health 2006;5:6. doi: 10.1186/1476-069X-5-6

29. Codd GA, Bell S, Kaya K, Ward C, Beattie KA, Metcalf JS. Cyanobacterial toxins, exposure routes and human health. Eur J Phycol 1999; 34:405-15.

30. Burke WA, Tester PA. Skin problems related to noninfectious coastal microorganisms. Dermatol Ther 2002;15:10-7.

31. World Health Organization (WHO). Guidelines for Safe Recreational Water Environments. Vol 1: Coastal and fresh waters. Geneva: WHO; 2003.

32. Hawser SP, Codd GA, Capone DG, Carpenter EJ. A neurotoxic factor associated with the bloom-forming cyanobacterium Trichodesmium. Toxicon 1991;29:277-8.

33. Lyngbya Task Force (LTF). Factors Associated with the Proliferation of the Toxic Cyanobacterium Lyngbya majuscula in Coastal Waters of Queensland: Triggers, Ecophysiology and Toxicology, Executive Summary 1. Brisbane: University of Queensland; 1998.

34. Fitzgeorge RB, Clark SA, Keevil CW. Routes of intoxication. In: Codd GA, Jefferies TM, Keevil CW, Potter E, editors. Detection methods for cyanobacterial toxins. Cambridge: The Royal Society of Chemistry; 1994. p. 69-74.

35. Metcalf JS, Richer R, Cox PA, Codd GA. Cyanotoxins in desert environments may present a risk to human health. Sci Total Environ 2012;421-422:118-23. doi: 10.1016/j. scitotenv.2012.01.053

36. Saqrane S, Ouahid Y, El Ghazali I, Oudra B, Bouarab L, del Campo F. Physiological changes in Triticum durum, Zeamays, Pisum sativum and Lens esculenta cultivars, caused by irrigation with water contaminated with microcystins: A laboratory experimental approach. Toxicon 2009;53:786-96. doi: 10.1016/j.toxicon.2009.01.028

37. MacKintosh C, Beattie KA, Klumpp S, Cohen P, Codd GA. Cyanobacterial microcystin-LR is a potent and specific inhibitor of protein phosphatases 1 and 2A from both mammals and higher plants. FEBS Lett 1990;264:187-92.

38. Abe T, Lawson T, Weyers JDB, Codd GA. Microcystin-LR inhibits photosynthesis of Phaseolus vulgaris primary leaves: implications for current spray irrigation practice. New Phytol 1996;133:651-8. doi: 10.1111/j.1469-8137.1996.tb01934.x

39. Pflugmacher S, Ame MV, Wiegand C, Steinberg CE. Cyanobacterial toxins and endotoxins their origin and their ecophysiolocical effects in aquatic organisms. Wasser Boden 2001;53:15-20.

40. Chen J, Song L, Dai J, Gan N, Liu Z. Effects of microcystins on the growth and the activity of superoxide dismutase and peroxidase of rape (Brassica napus L.) and rice (Oryza sativa L.). Toxicon 2004;43:393-400. doi: 10.1016/j. toxicon.2004.01.011

41. Kos P, Gorzo G, Suranyi G, Borbely G. Simple and efficient method for isolation and measurement of cyanobacterial hepatotoxins by plant tests (Sinapis alba L.). Anal Biochem 1995;225:49-53. doi: 10.1006/abio.1995.1106

42. Kurki-Helasmo K, Meriluoto J. Microcystin uptake inhibits growth and protein phosphatase activity in mustard (Sinapisalba L.) seedlings. Toxicon 1998;36:1921-6. doi: 10.1016/ s0041-0101(98)00114-7

43. McElhiney J, Lawton LA, Leifert C. Investigations into the inhibitory effects of microcystins on plant growth, and the toxicity of plant tissues following exposure. Toxicon 2001;39:1411-20. doi: 10.1016/S0041-0101(01)00100-3

44. M-Hamvas M, Mathe C, Molnar E, Vasas G, Grigorszky I, Borbely G. Microcystin-LR alters the growth, anthocyanin content and single-stranded DNase enzyme activities in Sinapis alba L. seedlings. Aquat Toxicol 2003;62:1-9.

45. Pflugmacher S, Wiegand C, Beattie KA, Codd GA, Steinberg CEW. Uptake of the cyanobacterial hepatotoxin microcystin- LR by aquatic macrophytes. J Appl Bot 1998;72:228-32.

46. Yin LY, Huang JQ, Huang WM, Li DH, Wang GH, Liu YD. Microcystin-RR-induced accumulation of reactive oxygen species and alteration of antioxidant systems in tobacco BY-2 cells. Toxicon 2005;46:507-12. doi: 10.1016/j. toxicon.2005.06.015

47. Pflugmacher S. Possible allelopathic effects of cyanotoxins, with reference to microcystin-LR, in aquatic ecosystems. Environ Toxicol 2002;17:407-13. doi: 10.1002/tox.10071

48. Codd GA, Metcalf JS, Beattie KA. Retention of Microcystis aeruginosa and microcystin by salad lettuce (Lactuca sativa) after spray irrigation with water containing cyanobacteria. Toxicon 1999;37:1181-5.

49. Mitrović SM, Allis O, Furey A, James KJ. Bioaccumulation and harmful effects of microcystin-LR in the aquatic plants Lemna minor and Wolffia arrhiza and the filamentous alga Chladophora fracta. Ecotoxicol Environ Safe 2005;61:345-52. doi: 10.1016/j.ecoenv.2004.11.003

50. Jarvenpaa S, Lundberg-Niinisto C, Spoof L, Sjovall O, Tyystjarvi E, Meriluoto J. Effects of microcystins on broccoli and mustard, and analysis of accumulated toxin by liquid chromatography-mass spectrometry. Toxicon 2007;49:865-74. doi: 10.1016/j.toxicon.2006.12.008

51. Crush JR, Briggs LR, Sprosen JM, Nichols SN. Effect of irrigation with lake water containing microcystins on microcystin content and growth of ryegrass, clover, rape, and lettuce. Environ Toxicol 2008;23:246-52. doi: 10.1002/ tox.20331

52. Chen J, Dai J, Zhang H, Wang C, Zhou G, Han Z, Liu Z. Bioaccumulation of microcystin and its oxidative stress in the apple (Malus pumila). Ecotoxicology 2010;19:796-803. doi: 10.1007/s10646-009-0456-5

53. Peuthert A, Chakrabarti S, Pflugmacher S. Uptake of microcystins-LR and -LF (cyanobacterial toxins) in seedlings of several important agricultural plant species and the correlation with cellular damage (lipid peroxidation). Environ Toxicol 2007;22:436-42.

54. Rahman M, Podder AK, van Hove C, Begum T, Heulin T, Hartmann A. Biological Nitrogen Fixation Associated with Rice Production. Dordrecht: Kluwer Academic Publisher; 1996.

55. Chen J, Xie P. Seasonal dynamics of the hepatotoxic microcystins in various organs of four freshwater bivalves from the large eutrophic lake Taihu of subtropical China and the risk for human consumption. Environ Toxicol 2005;20:572-84. doi: 10.1002/tox.20146

56. Chen J, Xie P. Tissue distributions and seasonal dynamics of the hepatotoxic microcystins-LR and -RR in two freshwater shrimps, Palaemon modestus and Macrobrachiumnipponensis, from a large shallow, eutrophic lake of the subtropical China. Toxicon 2005;45:615-25.

57. Negri AP, Bunter O, Jones B, Llewellyn L. Effects of the bloom forming alga Trichodesmium erythraeum on the pearl oyster Pinctada maxima. Aquaculture 2004;232:91-102. doi: 10.1016/S0044-8486(03)00487-3

58. Saker ML, Metcalf JS, Codd GA, Vasconcelos VM. Accumulation and depuration of the cyanobacterial toxin cylindrospermopsin in the freshwater mussel Anodontacygnea. Toxicon 2004;43:185-94. doi: 10.1016/j. toxicon.2003.11.022

59. Negri AP, Jones GJ. Bioaccumulation of paralytic shellfish poisoning (PSP) toxins from the cyanobacterium Anabaenacircinalis by the freshwater mussel Alathyria condola. Toxicon 1995;33:667-78. doi: 10.1016/0041-0101(94)00180- G

60. Chen J, Xie P, Guo LG, Zheng L, Ni LY. Tissue distributions and seasonal dynamics of the hepatotoxic microcystins-LR and -RR in a freshwater snail (Bellamya aeruginosa) from a large shallow, eutrophic lake of the subtropical China. Environ Pollut 2005;134:423-30.

61. White SH, Duivenvoorden LJ, Fabbro LD, Eaglesham GK. Influence of intracellular toxin concentrations on cylindrospermopsin bioaccumulation in a freshwater gastropod (Melanoides tuberculata). Toxicon 2006;47:497-509. doi: 10.1016/j.toxicon.2005.12.011

62. Magalhaes VF, Marinho MM, Domingos P, Oliveira AC, Costa SM, Azevdeo LO, Azevedo SMFO. Microcystins (cyanobacteria hepatotoxins) bioaccumulation in fish and crustaceans from Sepetiba Bay (Brasil, RJ). Toxicon 2003;42:289-95. doi: 10.1016/S0041-0101(03)00144-2

63. Malbrouck C, Kestemont P. Effects of microcystins on fish. Environ Toxicol Chem 2006;25:72-86.

64. Tencalla F, Dietrich D. Biochemical characterization of microcystin toxicity in rainbow trout (Oncorhynchus mykiss). Toxicon 1997;35:583-95. doi: .1016/S0041-0101(96)00153-5

65. Malbrouck C, Trausch G, Devos P, Kestemont P. Effect of microcystin-LR on protein phosphatase activity and glycogen content in isolated hepatocytes of fed and fasted juvenile goldfish Carassius auratus L. Toxicon 2004;44:927-32. doi: 10.1016/j.toxicon.2004.09.003

66. Gotz J, Probst A, Mistl C, Nitsch RM, Ehler E. Distinct role of protein phosphatase 2A subunit C[alpha] in the regulation of E-cadherin and [beta]-catenin during development. Mech Dev 2000;93:83-93.

67. Li XY, Wang J, Liang JB, Liu YD. Toxicity of microcystins in the isolated hepatocytes of common carp (Cyprinus carpio L.). Ecotoxicol Environ Saf 2007;67:447-51. doi: 10.1016/ j.ecoenv.2006.10.003

68. Palikova M, Navratil S, Tichy F, Sterba F, Marsalek B, Blaha L. Histopathology of carp (Cyprinus carpio L.) larvae exposed to cyanobacteria extract. Acta Vet Brno 2004;73:253-7. doi:10.2754/avb200473020253

69. Malbrouck C, Trausch G, Devos P, Kestemont P. Hepatic accumulation and effects of microcystin-LR on juvenile goldfish Carassius auratus L. Comp Biochem Physiol C Pharmacol Toxicol 2003;135:39-48.

70. Li XY, Chung IK, Kim JI, Lee JA. Subchronic oral toxicity of microcystin in common carp (Cyprinus carpio L.) exposed to Microcystis under laboratory conditions. Toxicon 2004;44:821-7. doi: 10.1016/j.toxicon.2004.06.010

71. Xie LQ, Xie P, Guo LG, Li L, Miyabara Y. Organ distribution and bioaccumulation of microcystins in freshwater fish at different trophic levels from the eutrophic Lake Chaohu, China. Environ Toxicol 2005;20:293-300.

72. Romo S, Fernandez F, Ouahid Y, Baron-Sola A. Assessment of microcystins in lake water and fish (Mugilidae, Liza sp.) in the largest Spanish coastal lake. Environ Monit Assess 2012;184:939-49. doi: 10.1007/s10661-011-2011-0

73. Kozlowsky-Suzuki B, Wilson AE, Ferrao-Filho AS. Biomagnification or biodilution of microcystins in aquatic foodwebs? Meta-analyses of laboratory and field studies. Harmful Algae 2012;18:47-55. doi: 10.1016/j. hal.2012.04.002

74. Peng L, Liu Y, Chen W, Liu L, Kent M, Song L. Health risks associated with consumption of microcystin-contaminated fish and shellfish in three Chinese lakes: Significance for freshwater aquacultures. Ecotoxicol Environ Saf 2010;73:1804-11. doi: 10.1016/j.ecoenv.2010.07.043

75. Papadimitriou T, Kagalou I, Bacopoulos V, Leonardos ID. Accumulation of microcystins in water and fish tissues: an estimation of risks associated with microcystins in most of the Greek Lakes. Environ Toxicol 2010;25:418-27. doi: 10.1002/tox.20513

76. Deblois CP, Aranda-Rodriguez R, Giani A, Bird DF. Microcystin accumulation in liver and muscle of tilapia in two large Brazilian hydroelectric reservoirs. Toxicon 2008;51:435-48. doi: 10.1016/j.toxicon.2007.10.017

77. Zhang D, Xie P, Liu Y, Qiu T. Transfer, distribution and bioaccumulation of microcystins in the aquatic food web in Lake Taihu, China, with potential risks to human health. Sci Total Environ 2009;407:2191-9. doi: 10.1016/j. scitotenv.2008.12.039

78. Ibelings BW, Chorus I. Accumulation of cyanobacterial toxins in freshwater ‘‘seafood’’ and its consequences for public health: A review. Environ Pollut 2007;150:177-92.

79. Saker ML, Eaglesham GK. The accumulation of cylindrospermopsin from the cyanobacterium Cylindrospermopsis raciborskii in tissues of the redclaw crayfish Cherax quadricarinatus. Toxicon 1999;37:1065-77. doi: 10.1016/S0041-0101(98)00240-2

81. Galvao JA, Oetterer M, Bittencourt-Oliveira Mdo C, Gouvea- Barros S, Hiller S, Erler K, Luckas B, Pinto E, Kujbida P. Saxitoxins accumulation by freshwater tilapia (Oreochromisniloticus) for human consumption. Toxicon 2009;54:891-4. doi: 10.1016/j.toxicon.2009.06.021

81. Berry JP, Jaja-Chimedza A, Davalos-Lind L, Lind O. Apparent bioaccumulation of cylindrospermopsin and paralytic shellfish toxins by finfish in Lake Catemaco (Veracruz, Mexico). Food Addit Contam Part A Chem Anal Control Expo Risk Assess 2012;29:314-21. doi: 10.1080/19 440049.2011.597785

82. Ferrao-Filho AS, Kozlowsky-Suzuki B. Cyanotoxins: Bioaccumulation and effects on aquatic animals. Marine Drugs 2011;9:2729-72. doi:10.3390/md9122729

83. Carmichael WW, Drapeau C, Anderson DM. Harvesting of Aphanizomenon flos-aquae Ralfs ex Born. and Flah. var. flos-aquae (Cyanobacteria) from Klamath Lake for human dietary use. J Appl Phycol 2000;12:585-95.

84. Jensen GS, Ginsberg DI, Drapeau C. Blue-green algae as an immuno-enhancer and biomodulator. JANA 2001; 3:24-30.

85. Lindermann B. Complicated Child? Simple Options. Ramona (CA): Ransom Hill Press; 1995.

86. Gilroy DJ, Kauffman KW, Hall RA, Huang X, Chu FS. Assessing potential health risks from microcystin toxins in bluegreen algae dietary supplements. Environ Health Perspect 2000;108:435-9. doi:10.2307/3454384

87. Draisci R, Ferretti E, Palleschi L, Marchiafava C. Identification of anatoxins in blue-green algae food supplements using liquid chromatography-tandem mass spectrometry. Food Addit Contam 2001;18:525-31.

88. Ballot A, Krienitz L, Kotut K, Wiegand C, Metcalf JS, Codd GA, Pflugmacher S. Cyanobacteria and cyanobacterial toxins in three alkaline rift valley lakes of Kenya - Lakes Bogoria, Nakuru and Elmenteita. J Plankton Res 2004;26:925-35. doi: 10.1093/plankt/fbh084

89. Ballot A, Krienitz L, Kotut K, Wiegand C, Pflugmacher S. Cyanobacteria and cyanobacterial toxins in the alkaline crater lakes Sonachi and Simbi, Kenya. Harmful Algae 2005;4:139-50. doi: 10.1016/j.hal.2004.01.001

90. Iwasa M, Yamamoto M, Tanaka Y, Kaito M, Adachi Y. Spirulina-associated hepatotoxicity. Am J Gastroenterol 2002;97:3212-3. doi: 10.1111/j. 1572-0241.2002.07145.x

91. Rapala J, Sivonen K, Luukkainen R, Niemela SI. Anatoxina concentration in Anabaena and Aphanizomenon under different environmental conditions and comparison of growth by toxic and non-toxic Anabaena-strains: A laboratory study. J Appl Phycol 1993;5:581-91. doi: 10.1007/BF02184637

92. Pereira P, Onodera H, Andrinolo D, Franca S, Araujo F, Lagos N, Oshima Y. Paralytic shellfish toxins in the freshwater cyanobacterium Aphanizomenon flos-aquae, isolated from Montargil reservoir, Portugal. Toxicon 2000;38:1689-702. doi: /10.1016/S0041-0101(00)00100-8

93. Ferreira FMB, Soler JMF, Fidalgo ML, Fernandez-Vila P. PSP toxins from Aphanizomenon flos-aquae (cyanobacteria) collected in the Crestuma-Lever reservoir (Douro river, northern Portugal). Toxicon 2001;39:757-61. doi: 10.1016/ S0041-0101(00)00114-8

94. Cox PA, Banack SA, Murch SJ, Rasmussen U, Tien G, Bidigare RR, Metcalf JS, Morrison LF, Codd GA, Bergman B. Diverse taxa of cyanobacteria produce beta-Nmethylamino- L-alanine, a neurotoxic amino acid. Proc Nat Acad Sci USA 2005;102:5074-8.

95. Lawrence JF, Niedzwiadek B, Menard C, Lau BP, Lewis D, Kuiper- Goodman T, Carbone S, Holmes C. Comparison of liquid chromatography/mass spectrometry, ELISA, and phosphatase assay for the determination of microcystins in blue-green algae products. J AOAC Int 2001;84:1035-44.

96. Yu FY, Liu BH, Chou HN, Chu FS. Development of a sensitive ELISA for the determination of microcystins in algae. J Agric Food Chem 2002;50:4176-82. doi: 10.1021/ jf0202483

97. Hoeger SJ, Dietrich DR. Possible health risks arising from consumption of blue-green algae food supplements. Sixth International Conference on Toxic Cyanobacteria; 21-27 June 2004. Bergen, Norway. Abstract p. 30.

98. Saker ML, Jungblut AD, Neilan BA, Rawn DFK, Vasconcelos VM. Detection of microcystin synthetase genes in health food supplements containing the freshwater cyanobacterium Aphanizomenon flos-aquae. Toxicon 2005;46:555-62. doi: 10.1016/j.toxicon.2005.06.021

99. Schaeffer D, Malpas P, Barton L. Risk assessment of microcystin in dietary Aphanizomenon flos-aquae. Ecotoxicol Environ Saf 1999;44:73-80.

100. Azevedo SM, Carmichael WW, Jochimsen EM, Rinehart KL, Lau S, Shaw GR, Eaglesham GK. Human intoxication by microcystins during renal dialysis treatment in Caruaru- Brazil. Toxicology 2002;181-182:441-6. doi: 10.1016/S0300-483X(02)00491-2

101. Fawell J, James C, James H. Toxins from Blue-Green Algae: Toxicological Assessment of Microcystin-LR and a Method for Its Determination in Water. Marlow: Water Research Centre; 1994.

102. Humpage AR, Hardy SJ, Moore EJ, Froscio SM, Falconer IR. Microcystins (cyanobacterial toxins) in drinking water enhance the growth of aberrant crypt foci in the mouse colon. J Toxicol Environ Health A 2000;61:155-65.

103. Botha N, Van de Venter M, Downing TG, Shepard EG, Gehringer EG. The effect of intraperitoneally administered microcystin-LR on the gastrointestinal tract of Balb/c mice. Toxicon 2004;43:251-4.doi:10.1016/j.toxicon.2003.11.026,

104. Maidana M, Carlis V, Galhardi FG, Yunes JS, Geracitano LA, Monserrat JM, Barros, DM. Effects of microcystins over short- and long-term memory and oxidative stress generation in hippocampus of rats. Chem Biol Interact 2006;159:223-4.

105. Žegura B, Volčič M, Lah TT, Filipič M. Different sensitivities of human colon adenocarcinoma (CaCo-2), astrocytoma (IPDDC-A2) and lymphoblastoid (NCNC) cell lines to microcystin-LR induced reactive oxygen species and DNA damage. Toxicon 2008;52:518-25. doi: 10.1016/j. toxicon.2008.06.026

106. Soares RM, Cagido VR, Ferraro RB, Meyer-Fernandes JR, Rocco PRM, Zin WA, Azevedo SMFO. Effects of microcystin-LR on mouse lungs. Toxicon 2007;50:330-8. doi: 10.1016/j.toxicon.2007.04.003,

107. Milutinović A, Zorc-Pleskovič R, Petrovič D, Zorc M, Šuput D. Microcystin-LR induces alterations in heart muscle. Folia Biol (Praha) 2006;52:116-8.

108. Nobre ACL, Jorge MCM, Menezes DB, Fonteles MC, Monteiro HSA. Effects of microcystin-LR in isolated perfused rat kidney. Brazil J Med Biol Res 1999;32:985-8.

109. Milutinović A, Sedmak B, Horvat-Žnidaršić I, Šuput D. Renal injuries induced by chronic intoxication with microcystins. Cell Mol Biol Lett 2002;7:139-41.

110. Milutinović A, Živin M, Zorc-Plesković R, Sedmark B, Šuput D. Nephrotoxic effects of chronic administration of microcystins-LR and -YR. Toxicon 2003;42:281-8.

111. Ding XS, Li XY, Duan HY, Chung IK, Lee JA. Toxic effects of microcystis cell extracts on the reproductive system of male mice. Toxicon 2006;48:973-9. doi: 10.1016/j. toxicon.2006.07.039

112. Li H, Xie P, Li G, Hao L, Xiong Q. In vivo study on the effects of microcystin extracts on the expression profiles of proto-oncogenes (c-fos, c-jun and c-myc) in liver, kidney and testis of male Wistar rats injected i.v. with toxins. Toxicon 2009;53:169-75. doi: 10.1016/j.toxicon.2008.10.027

113. Ufelmann H, Kruger T, Luckas B, Schrenk D. Human and rat hepatocyte toxicity and protein phosphatase 1 and 2A inhibitory activity of naturally occurring desmethylmicrocystins and nodularins. Toxicology 2012;293:59-67. doi: 10.1016/j.tox.2011.12.011

114. Novakova K, Babica P, Adamovsky O, Blaha L. Modulation of gap-junctional intercellular communication by series of cyanobacterial samples from nature and laboratory cultures. Toxicon 2011;58:76-84.doi:10.1016/j.toxicon.2011.05.006

115. Chen J, Xie P, Li L, Xu J. First identification of the hepatotoxic microcystins in the serum of a chronically exposed human population together with indication of hepatocellular damage. Toxicol Sci 2009;108:81-9. doi: 10.1093/toxsci/kfp009

Archives of Industrial Hygiene and Toxicology

The Journal of Institute for Medical Research and Occupational Health

Journal Information


IMPACT FACTOR 2017: 1.117
5-year IMPACT FACTOR: 1.335



CiteScore 2017: 1.24

SCImago Journal Rank (SJR) 2017: 0.341
Source Normalized Impact per Paper (SNIP) 2017: 0.494

Cited By

Metrics

All Time Past Year Past 30 Days
Abstract Views 0 0 0
Full Text Views 269 269 21
PDF Downloads 132 132 19