Reddy M. R. K, Mastan S. A. Algal Toxins and their Impact on Human Health. Biomed Pharmacol J 2011;4(1)
Manuscript received on :November 12, 2010
Manuscript accepted on :December 20, 2010
Published online on: 26-11-2015
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M. Radha Krishna Reddy and S. A. Mastan

P.G Department of Biotechnology and Microbiology, DNR College, PG Courses and Research Centre, Bhimavaram - 534 202 India.

Abstract

Different species of fresh water Blue Green Algae namely Anabaena sp., Aphanizomenon sp., Coleosphaerium sp., Gloeotrichia sp, Lyngbea sp., Microcystis sp.and Nodularia sp. are capable of producing a number of toxins. These toxins are secondary metabolites which are highly toxic to human beings and other animals. These toxins belong to different classes such as cyclic peptides, Alkaloides and Lipopolysaccharides.

Keywords

Blue Green Algae; Toxins; Human Health

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Introduction

Algal toxins are organic molecules produced by a variety of algal species from fresh, brackish and marine waters (Falconer, 1993). Over the past three decades, the occurrence of harmful toxic algal incidents has increased in many parts of the World (  Anderson , 1989 and Shum way, 1990). Many bloom forming species of algae are capable of producing biologically active secondary metabolites which are highly toxic to human health and other animals (Pearson et al., 2010). Cyanobacteria can produce different type of Cyanotoxins which belongs to four major classes namely Neurotoxins, Hepatotoxins, Cytotoxins, Dermatotoxins and Lipo polysaccharides. The present review reports an overview of various toxins of algae and their impact on human health and other animals.

Eutrophication       

Eutrophication is a process whereby water bodies such as lakes, estuaries, or slow moving streams receive excess nutrients that stimulate excessive plant growth such as algae, periphyton attached algae and naissance plant weeds. This enhanced plant growth often called an Algal Bloom and it reduces the dissolved oxygen, decreased transparency of light, bottom phytoplankton died in the water. When dead plant material decomposes and can cause other organisms to die (Thyagarajan et al., 2007).

Cyanobacteria

Cyanobacteria also known as Blue Green Algae Gram-Negative, Photo synthetic, prokaryote found in a variety of habitats such as Fresh, Brackish, marine, hyper saline, volcanic ash, desert sand, rocks  and terrestrial environments. (Chorus & Bartram 1999). They play important role in the biological cycling of elements and show diversity of aquatic communities. Cyanobacteria have both beneficial and detrimental properties. When judged from human perspective the extensive growth of Cyanobacteria can create a considerable nuisance for management of inland waters and they may also release various toxic substances in to the water. The water quality problems caused by dense population of Cyanobacteria are intrinsic, many and various and can have a great impact on the health of humans and other animals. (Masango,2007).

Toxins produced by Blue Green Algae

Of the more than 50 genera of blue green algae at least 8 have exhibited toxic characteristics of these include Anabaena sp., Aphanizomenon sp., Coelosphaerium sp., Gleotrichia sp., Lyngbea sp., Nodularia sp., and Nostoc sp. (Mike Collins, 1978). The incidents of toxicity of these blue green algae have been reported by Schwimmer and Schwimmer 1964; 1968). The earliest reports of Cyanobacteria poisoning may have been around 1,000 years ago. When general Zlu-Ge-Ling reported mortalities in troops that drank water from a river in southern China. But first known incidents of Cyanobacteria toxin poisoning was from an Australian lake in 1878 (Chorus and Bartram,1999, Francis, 1878 )

Cyanobacteria produce variety of toxins called cyanotoxins. Cyanotoxins are diverse group of natural toxins. In spite of their aquatic origin most of the Cyanobacteria that have been identified, so far appear to be more hazardous to humans and other aquatic animals   ( Carmichel, 1992 ;  Chorus  and Bartrman,1999 ;  Falconer and Humpage , 2005 and Codd et al., 2005a).

Neurotoxins

Neurotoxins are produced by different genera of Cyanobacteria including Anabaena sp, Aphanizomenon sp, Microcystis sp, Planktothrix sp, Raphidopsis sp, Cylindrospermium sp, Phormidium sp, and Oscillatoria sp.

Neurotoxins of Oscillatoria sp. and Anabaena sp. have been responsible for animal poisoning (Carmichael 1997; Braind et al., 2003; John.,H; Rodgers.JR, 2008). Neurotoxins usually cause acute effects in vertebrates including rapid paralysis of the peripheral skeletal and respiratory muscles. Neurotoxins affect the nervous system of the animals. Anatoxin-A inhibits transmission at the neuromuscular junction by molecular mimicry of the neurotransmitter, Acetylcholine ( John.H  &Rodgers JR  et al.,  2008)

Hepatotoxins

The cyclic penta peptide Nodularin is most commonly produced from the filamentous, planktonic, Cyanobacterium, Nodularia spumigena. This species generally form toxic blooms in brackish and estuarine environment (Pearson et al.,2010). Nodularin is a potent hepatotoxin for humans and other animal. It induces liver hemorrhage in mice, when it injected in artificial way. The toxic effects of nodularin are primarily associated with the hepatic cells due to active transport of the toxin to liver via the bile acid, multi specific organic anion transporters (Pearson et al., 2010; Runnegar et al., 1995). The consumption of N.spumigena may cause massive liver hemorrhage in animals (Nehring.,1993; Carmichael and Eshedor.,1988; Carmichel.,1994; Francis 1878).

Saxitoxins

Saxitoxins are heterocyclic guanidine neurotoxins act like carbamate pesticides  produced by different fresh water algae like Anabaena circinalis, Aphanizomenon., Aphanizomenon gracilie., Lyngbea wolleri  are responsible for shell fish poisoning. Blooms of these toxic species have led to mass kills of fish, native mammals and live stock as well as the contamination of fresh water resources. ( Negri Jones.,GJ et al 1995; Sawyer Gentile., 1968). Saxitoxin bind to site I on the voltage –dependent Sodium channel inhibiting channel conductance and thereby causing blockade of neuronal activity

Paralytic shell fish poisoning symptoms generally onset with in 30 min of ingestion and invariably begin with a tingling or burning of lips, tounge and throat increase to total numbness of face (Lewellyn.,2006). The saxitoxin causes several health problems in humans include perspiration, vomiting, diarrhea. In case of acute poisoning numbness may be spread to neck and extremities and progress to muscular weakness, loss of motor coordination, and finally leads to paralysis (Lewellyn, 2006 ).

Lipopolysacchrides (LPS)

Lipopolysaccharides are known as irritant toxins and are generally found in the outer membrane of the cell wall of Gram-negative bacteria, including Cyanobacteria, where they form complexes with proteins and phospholipids. It is generally the fatty acid component of the LPS molecule that elicits an irritant allergic response in humans and mammals. Cyanobacterial LPS are considerably less potent than LPS from pathogenic Gram-negative bacteria such as Salmonella (Chorus and Bartram, 1999 and Masango,2007). LPS is a potent activator of macrophages and can results in the production of cytokines and growth factors.

Cylindrospermopsin

Cylindrospermopsin is a polyketide derived alkaloid was first discovered in 1979, when 148 people were hospitalized with the symptoms of hepatoenteritis on palm island (Queen land) Australia, it was due to C.racibarskii.( Bourkae et al., 1980; Byth et al., 1980; Hawkins et al 1985; Ohtaic et al.,1992). It also effects domestic animals. ( Saker et al.,1999). Generally it is a cytotoxin that blocks glutathione, protein synthesis, and cytochrome p450.  (Runnegar et al.,1995; Runnegar et al.,1994; Froscio et al., 2003). It also interfering with systems of Liver, Nerves, Thymus and Heart and is considered a potential carcinogen. (Runnegar et al.,1995; Runnegar et al., 1994; Runneagr et al.,2002; Kiss et al.,2002).

Cylindrospermopsin is produced by eight fresh water Cyanobacterial members includes Cylindrospermopsis raciborskii, Aphanizomenon ovalisporum, Aphanizomenon flos- aquae Anabaena bergi, Anabaena lapponica, Lyngbya  wollei, Rhaphidiopsis carvata, Umezakia natans. Out of these eight members Cylindrospermopsis raciborskii presents a major problem for eater management on globally. ( Neilan et al.,2003).

Anatoxins

There are three families of cyanobacterial neurotoxins are known namely Anatoxin-a and Homoanatoxin-a, Anatoxin-a(s), Saxitoxin ( Mahmood & Carmichael 1987; Carmichael et al., 1992). Anatoxin-a is one of the neurotoxic alkaloids tht have been produced from cyanobacteria include Anabaena, Planktothrix,(Oscillatoria), Aphanizomenon, Cylindrospermum, Microcystis spp. Anatoxin-a is a bi cyclic secondary amine that mimics the neurotransmitter acetyl choline and binds to the nicotinic acetyl choline receptor at the axon terminal at the neuro muscular interface Botana, 2007.Huisman et al., 2005. Binding of anatoxin- a is irreversible, the sodium channel is locked open, becomes over stimulate, fatigued and eventually paralyzed. ( Carmichael, 1975). Anatoxin-a exposure results in a lack of oxygen to the brain, subsequent convulsions and death by suffocation.

Homo Anatoxin produced by Oscillatoria formosa , it is a methyl analogue of  Anatoxin-(A)  (Carmichael 1992)

Anatoxin-a (s) produced by A.flos-aquae, ( Matsunaga et al., 1989)  and induced salivation in mice by which it can be differentiated from other cyanobacterial neurotoxins. It acts as an irreversible anti cholinesterase inhibitor (   Mahmood  &  Carmichael, 1987).

Contactdermatitis

Allergic dermal reactions of varying severity have been reported from a number of fresh water cyanobacterial genera. Anabaena sp., Aphanizomenon sp., Nodularia sp., Oscillatoria sp., Gleotrichia sp.,  after  recreational exposure. Reports from USA have recorded allergic reactions from recreational exposure and the cyanobacterial pigment, Cyanophycin has been shown to be responsible in one case ( Cohen and Reif et al., 1953). Skin irritations were a frequent symptoms found in an epidemiological study by Pilotto et al (1997). Heise (1949) described that  ocular and nasal irritation in swimmers exposed to Oscollatoriaceae. Cyanobacterial toxins can cause severe allergic reactions in sensitive individuals (Cohen and  Reif et al.,  1953)

Microcystins

Microcystins produced by Microcystis aeruginosa., Microcystis viridis., Aphanizomenon flos-aquae.,  Oscillatoria haplosporium and Anabaena species are associated with Microcystins. M.aeruginosa are most frequently associated with the algal blooms and associated with hepatotoxicity. (Chorus&Bartram et al., 1999 ;  Hitzfeld and  Hoger, 2000). Microcystins are cyclic   hepta peptides with variable aminoacids at seven different positions. The microcystins are generally associated with Hepato toxicity ( Chorus and Bartram ,1999.)

The name microcystis derived from the toxins that were first isolated from Microcystis.aeruginosa. The toxicity of microcystis is due to their strong binding to protein phosphatases ( Chorus and Bartram 1999; Hitzfeld,and Hoger et al., 2000; Pilotti et al.,1999; Tervola and Eriksson &Brautigan 1994; Runnegar&Gerdes et.al 1991; Runnegar&Berndt et al 1995; Dawson 1998.)

Up on ingestion, Microcystin is transported to liver by organic anion transport proteins where they exert their toxicity via inhibition of proteins. Inhibition of protein phosphates can lead to excessive phospharylation of structural filaments, subsequent cytoskeletal degradation and breakdown of hepatic ultra structure. ( Eriksson and Toivola et al 1990; Sahin & Tencalla et al 1995). Neighboring cells and sinusoidal capillaries causes blood to become pooled in the liver tissues. This ultimately results in local tissue damage, organ failure and hemorrhagic shock.

References

  1. Anderson.D.M., Toxical algal blooms and red tides; aglobal perspective in red tides in biology, Environmental sciences and toxicology, (1989).
  2. Banker.R; Carmeli.S; Werman.M., Teltsch.B., Porat.R.; Sukenik.A. Uracil moiety is required for toxicity of the cyanobacteria  hepatotoxin cylindrospermopsin . J.toxicol. Environ. Health part A 62, 281-288, (2001).
  3. Byh.S., Palm island mystery disease Med.J.Aust 2, 40-42, (1980).
  4. Bourke.A.T.C., Hawes.R.B., Neilson.A., Stallman.N.B. An out break of hepatoenteritis (the palm island mystery diseases.) globally caused by algal intoxication. Toxicon 21, 45-48, (1983)
  5. Briand.J.F.S. Jaequet.,  C.Bernard and J.F. Humberd.  Health hazards for terrestrial vertebrates from toxic cyanobacteria in surface water ecosystem. Vet. Res 34:361-377, (2003).
  6. Botana.,L; Phycotoxins chemistry and Biochemistry. Black well publishing ISBN 13: 978-0-8138-2700-1-.345 pp., (2007).
  7. Chorus.I., Bartram.J., Toxic cyanobacteria in water. A guide to their public health consequences, monitoring and management, E&FN Spon, London, UK, (1999).
  8. Carmichael.w.w., cyanobacteria secondary metabolities- the cyanotoxins. A journal of applied bacteriology 72:445-459, (1992).
  9. Chorus.I& Bartam.J. Toxic cyanobacteria in water. A guide to their public health consequences, monitoring and management Ist Ed London; E&FN spon.(1999)
  10. Codd.G.A.,  J.Lindsay.F.M.,  Young.L.,  Morrison.L.f.,  Metcalf.JS.,  Harmful cyanobacteria: from man mortalities to management measures in J.Haisman H.C.P. Matthisjis and P.M Visser ( Edu), Harm full cyanobacteria springer, Dordrecht, The Netherland PP 1-23,(2005)
  11. Carmichael.W.W.,  Erans.W.R ., Yin.QQ.,  Bell.P.,  Moczy.Dolwsky.  E. Evidence for paralytic Shell fish poisonins in the fresh water cyanobacteria Lygbya.Wollei( Farlow.N Gomont), Comb. Nov.Appl.Environ. Microbial. 63, 3104-3110 (1997)
  12. Chorus.I & Bartram.J.  Toxic cyanobacteria in water; a guide to public health consequences, monitoring and manbagement. London: E&FN Spon (1999).
  13. Chorus.I & Bartran.J. Toxic cyanobacteria in water .a guide to the public health consequences in monitoring and management Ist  Ed London E& FN ,Spon( 1999)
  14. Chorus.I&Batram.J Toxic cyanobacteria in water a guide to public health consequences monitoring and management Ed London E& FN Spon (1999).
  15. Carmichael., W.W; Eschedor., J.T; Patterson.,G.M; Moore.R.E; Toxicity and partial structureof a hepato toxic peptide produced by the Cyanobacterium Nodularia spumigena Mertens emend L 575 from NewZealand. Appl.Environ.Microbial, 54, 2257-2263, (1988).
  16. Carmichael,w.w. The toxins of Cyanobacteria Sci.am 64-72 (1994).
  17. Cohen.,S.G; reif, Cyanobacteria cuteneous sensitization to blue green algae Journal of Allergy 24:452-457., (1953).
  18. Dawson., R.M.The toxicology of Microcystins Toxicon 36,953-962., (1998).
  19. Erikson., J.E; Toivola.,D ; Meriluoto.,J.A; Karaki.,H; han.,Y.G; Hartshrone.,D; Hepatocyte deformation induced by cyanobacterial toxins reflects inhibition of protein phosphatases Biochem. Biophys.Res.Commun.173., 1347-1353., (1990).
  20. FrocisoS.M;  Humpage,A.R;  Burcham,P.C;  Falconer.I.R., cylindro spermopsin-induced protein synthesis inhibition and its dissociation from acute toxicity in mouse hepatocytes Environ toxicol water Qual. 18, 243-251, (2003).
  21. Francis.G   poisonous Australian lake. Nature 18, 11-12., (1878)
  22. Falconer.,I.R; Humpage.,A.R; Health risk assessment of cyanobacterial (Blue Green Algal) toxins in drinking water. International Journal of Environmental Research and Public Health 2:43-50., (2005).
  23. Falconer.I.R.,  Algal toxin in sea foods and drinking water .SanDiego., Accademic press.pp 22k. (1993)
  24. Hawkins.P.R., Runnegar.M.T.C., Jaksson.A.R.B., Falconer.I.R., Severe hepato toxicity caused by the toxical cyanobacteria (BGA)cylindrospermopsis .racibarskii(WoloSzynska). Seenaya and subbaraju isolated from a domestic water supply resvoir. Applied environmental Microbiology 50:1292-1295, (1985).
  25. Huisman.,J; Matthijs.,H; and Visser.,P; Harmful Cyanobacteria AQE C3. Springer.Netherlands ISBN-1-4020-3009-6.241 pp,  (2005).
  26. John.H., Rodgers.Jr. Algal toxins in pond aqua culture, SRAC Publication No. 4065
  27. Kiss.T., Vehovsky.A., Hiripi.L., Kovacs.A., Boros.L membrabe effect of toxins isolated from cyanobacterial cylindrospermopsis.raciborskii on identified molluscan neurons Comp. BioChem.Physiol.C: Toxical Pharmacol. 131,167-176  (2002).
  28. Leanne person; Trochomihali; Michelle Moffitt;  Ralf Kellman; and Brett Neilan; 8, 1650-1680; Doi: 10.3390/md 805,650, Mar. drugs (2010)
  29. Llewellyn.L.E., Saxitoxin , a toxic marine natural product that targets a multitude of receptors Nat.Prod.Rep. 23,200-222, (2006).
  30. Mahmood.,N.A;Carmichel., W.W;Anatoxin-a(s), an anticholineesterase from Cyanobacterium Anabaena-flos-aquae NCR-525-17. Toxicon 25:1221-1227.,( 1987).
  31. Masango,M.G.;A comparative analysis of thecytotoxicity of cynotoxinsusing in vitro (cell culture)and invivo (Mouse) Assay ,Thesl submitted the University of Pretiria,pp-1-93.(2007)
  32. Norris, R.L ., Eagleshman, G.K ;  Pierens. P .,  Snow, G.A., Smith , N.J., Uniswell, R.K., Seawright, A.A.,  Moore, N.M.R   Deocy cylindrospermopsin, an analogus of cylindrospermopsin from cylindrospermopsis.racibarskii. Environ. Tocal. Water Qual 14, 163-165, (1999).
  33. Neilan.BA., Salker.M.L., Fastner.J., Toraokne.A ., Burns.B.P. Phylogeography of the invasive cyanobacteria cylindrospermopsis.raciborskii Mol.Ecd, 12,133-140, (2003)
  34. Nehring.S 1993.,  Carmichael &Eschdor  1988, Carmichael 1994;  Francis (1878).
  35. Negri .A.P. Jones .G.J., Hind marsh.M., Sheep mortality associated shell fish posoining from Cyanobacteria  Anabaena.circinals. Toxiccon 33, 1321-1329, (1995).
  36. Neihring.,S; Mortality of dogs associated with a mass development of Nodularia speumigena (cyanophyceae) in a brakscih lake at the Jerman north sea coast.J. Plankton Res. 15, 867-872., (1993).
  37. Ohtani.I.,  Moore.R.E.,  Runnegar.M.T.C.,  Cylindrospermopsin.potential hepato toxin from the blue green algae cylindrospermopsis. Raciborskii J.A.M Chem Soc 114, 7914-7942 , (1992).
  38. Pilotto,L.S; Douglas,R.S; Burch,M.D; Cameron.,s; Beers.,M; Rough.,g.r; Robinson.,P; Kirk.,K; Cowie.,C.T; Hardiman.,S; Moore.,C; Health effects of recreational water related activities.Australia & Newzealand Journal of Public Health 21:562-266., (1997).
  39. Runnegar,M.T; Kong,S.M; Zhong,Y.Z; Lu, S.C. Inhibition of reduced glutathione synthesis by cyanobacteriall alkaloid Cylindrospermopsin in cultured rat hepatocytes. Biochem.Pharma. Col.49, 219-225., (1995)
  40. Reyero.M.,  Cacho.E.,  Martinez. Vazquez.J.,  Marina.A.,  Fraga.S.,  Franco.J.,  Evidence of saxitoxin derivatives of causative agents in the 1997 mass mortality of monk seals in the Kate Blame penionsula Nat. Toxins 7,311-315.,(1999)
  41. Runnegar.M.T.C., Kongs.M Zhong. Y.N.,  Lu.sc., inhibition of reduced glutathione synthesis by cyanobacterial alkaloid cylindrospermopsin, alkaloid from cylindrospermopsin is cultured at rat hepatocytes . Biochem. Biophys.Res. Commun 201,235-241 (1994).
  42. Runnegar.M.T.C.,  Kongs.M  Zhong. Y.N., Lu.sc., the role of glutathione in the toxicity of novel cyanobacterial alkaloid cylindrospermopsin in cultured rat hepatocytes  Biochem. Biophys., Res. Commun, 201, 235-241 , (1994).
  43. Runnegar.M.T.C.,  Xie. C.,  Sindu B.B.,  Wallace.G.A.,  Wein.Ref. S.M., Kuhlenkemp.J., invitro hepatotoxicity of the cyanobacterial alkaloid cylindrospermopsis and related synthetic analogus. Toxicol, Sci.67, 81-87, (2002).
  44. Runnegar,M; Berndt.,N; Kaplowitz.,N; Microcystin uptake and inhibition of protein phosphatases: effects of chemo protectents and self inhibition in relation to known hepatic transporters. Toxicol. Appl. Pharmacol. 134, 264-272.,( 1995).
  45. Runnegar.M.T.C.,  Kongs.M  Zhong. Y.N., Lu.Sc; Inhibition of reduced Glutathione synthesis by cyanobacterial alkaloid Cylindrospermopsin in cultured rat hepatocytes.
  46. BioChem.Physiol.C: Toxical Pharmacol 49, 219-225., 1995.
  47. Runnegar.M.T; Kongs.,M; Zhong., Y.Z; Ge.ZL; Lu., Sc; The role of glutathione in the toxicity of novel cyanobacterial alkaloid Cylindrospermopsin in cultured rat hepatocytes. Biochem. Biophys. Res. Commun.201, 235-241., (1994).
  48. Runnegar.,M; berndt.,N; Kaplowitz., N; Microcystin up ptake and inhibition of protein phosphatase: Effects of chemo protectents and self inhibition in relation to known hepatic transporters. Toxicol. Appl.Pharmacol. 1341 264-272., (1975).
  49. Sahin., A;  Tencalla.,F.G; Dietrich.,D.R; Mez.,K; Naegeli.,H; Enzymatic analysis of liver samples from rainbow trout for diagnosis of Blue-green algae induced toxicosis.Am.J.Vet Res. 56, 1110-1115., (1995)
  50. Sawyer.P.J., Gentile.J.H.,  Sanner.J.J.J., Demonstration of toxin from Aphanisomenon. Flos-aquae(L) Ralfs. Cam.J. Microbial 14,1199-1204, (1968).
  51. Schwimmer.D& Schwimmer.M.,  Medical aspects of physiology  P.279-358 in D.Jackson(ed), algae, man at the environment. Syracuse university press, Syracuse, NY (1968).
  52. Schwimmer.D & Schwimmer.M ., Algae and medicine P.368-412. in D.Jackson(ed), algae and man. Plenum publishing of Newyork (1964).
  53. Skulberg.O.M.,  Carmichael.W.W.,  Andersnon.R.A.,  Matsunaga.S.,  Moore.R.E., Skulberg.R., investigation of neurotoxic oscillatorian strain (cyanophyceae) and its toxin. Isolation and characterization of homoanatoxin-a. Environmental toxicology and chemistry 11:321-329., (1992)
  54. Salker.M.L, Thomas.A.P., Norton.J.H. Cattle mortality attributed to the toxic cyanobacterium cylindrospermopsis.racibarskii is an out break region of Northern Queens land Environ. Toxical. Water Qual. 14,179-182, (1999).
  55. Terao.K., Ohmori.S., Lagarshi.I., Watanabe.M.F., Harade.K.I.,Watanabae.M. Electron microscopic studies can experimental poisoning in mice induced by cyclindrospermopsin isolated from (Blue green algae) Umazakia.natans . Toxicon 32,833-843, (1994).
  56. Thyagarajan.G., Ramesh.K., Rajakumar.D , water technology centre., department of Agronomy, tamilnadu agricultural university, Cimbatore, Science tech (2007)
  57. Toivola., D.m; Erikson.,J.E; & Brautigen.,D.L. Identification of protein phosphatase 2A as the primary target for Microcystin-LR in rat liver homogenates FEBS LETT 344,175-180. (1994)
  58. Wiegand.C., Salmer.M.L., Pflugmacher.S., Ecotoxicological effects of selected cyanobacteria secondary metabolites ; a short preview. Toxicol. Appl. Pharmacol .203,201-218, (2005).
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