Scientific Opinion on marine biotoxins in shellfish – Emerging toxins : Ciguatoxin group 1 EFSA Panel on Contaminants in the Food Chain

The EFSA Panel on Contaminants in the Food Chain (CONTAM Panel) assessed the risks to human health related to the consumption of ciguatoxin (CTX)-group toxins in fish. CTX-group toxins occur in fish as a result of biotransformation of precursor gambiertoxins produced by the benthic dinoflagellate Gambierdiscus toxicus. CTX-group toxins cause ciguatera fish poisoning. They are mainly found in Pacific, Caribbean and Indian Ocean regions and are classified as Pacific (P), Caribbean (C) and Indian Ocean (I) CTX-group toxins. Recently CTX-group toxins were identified for the first time in fish in Europe. Currently there are no regulatory limits for CTX-group toxins in fish in Europe, but the regulation requires that no fish products containing CTX-group toxins are placed on the market. The toxicological database for CTX-group toxins is limited, comprising mostly acute toxicity studies. In view of the acute toxicity of CTX-group toxins the CONTAM Panel considered establishing an acute reference dose (ARfD). However, due to the very limited quantitative data both in experimental animals as well as related to human intoxications, the CONTAM Panel concluded that the establishment of an oral ARfD was not possible. Based on case reports on human intoxications it appears that a concentration of 0.01 μg P-CTX-1 equivalents/kg fish is expected not to exert effects in sensitive individuals when consuming a single fish meal. The mouse bioassay (MBA) has been widely used to detect CTX-group toxins. However, due to insufficient detection capability and ethical concerns the MBA is not considered an appropriate method. In vitro (cytotoxicity and receptor binding) assays have been developed as alternative, but they need further development. Liquid chromatography-tandem mass spectrometry methods can be of value for the quantification of CTX-group toxins, but certified reference standards and reference materials need to be provided to allow method development and (inter-laboratory) validation.

[1]  T. Yasumoto,et al.  Ciguatera incidence and fish toxicity in Okinawa, Japan. , 2010, Toxicon : official journal of the International Society on Toxinology.

[2]  G. Shaw,et al.  Human fatality associated with Pacific ciguatoxin contaminated fish. , 2010, Toxicon : official journal of the International Society on Toxinology.

[3]  G. Shaw,et al.  Establishing a public health analytical service based on chemical methods for detecting and quantifying Pacific ciguatoxin in fish samples. , 2010, Toxicon : official journal of the International Society on Toxinology.

[4]  R. Lewis,et al.  Rapid extraction combined with LC-tandem mass spectrometry (CREM-LC/MS/MS) for the determination of ciguatoxins in ciguateric fish flesh. , 2009, Toxicon : official journal of the International Society on Toxinology.

[5]  E. Levin,et al.  Repeat exposure to ciguatoxin leads to enhanced and sustained thermoregulatory, pain threshold and motor activity responses in mice: relationship to blood ciguatoxin concentrations. , 2008, Toxicology.

[6]  R. Dickey Ciguatera Toxins: Chemistry, Toxicology, and Detection , 2008 .

[7]  C. Tamaru,et al.  Detection of ciguatoxin in fish tissue using sandwich ELISA and neuroblastoma cell bioassay , 2008, Journal of clinical laboratory analysis.

[8]  Y. Hokama,et al.  Development of an enzyme‐linked immunosorbent assay for the detection of ciguatoxin in fish tissue using chicken immunoglobulin Y , 2008, Journal of clinical laboratory analysis.

[9]  G. Nikolaidis,et al.  Morphological identification of two tropical dinoflagellates of the genera Gambierdiscus and Sinophysis in the Mediterranean Sea , 2008 .

[10]  H. Darius,et al.  Ciguatera risk assessment in two toxic sites of French Polynesia using the receptor-binding assay. , 2007, Toxicon : official journal of the International Society on Toxinology.

[11]  Michael V Arnett,et al.  Ciguatera fish poisoning: impact for the military health care provider. , 2007, Military medicine.

[12]  W. Catterall,et al.  Voltage-gated ion channels and gating modifier toxins. , 2007, Toxicon : official journal of the International Society on Toxinology.

[13]  Y. Bentur,et al.  Ciguatoxin-like substances in edible fish on the eastern Mediterranean* , 2007, Clinical toxicology.

[14]  J. Ramsdell,et al.  Optimization of ciguatoxin extraction method from blood for Pacific ciguatoxin (P-CTX-1). , 2007, Toxicon : official journal of the International Society on Toxinology.

[15]  R. Lewis Ciguatera: Australian perspectives on a global problem. , 2006, Toxicon : official journal of the International Society on Toxinology.

[16]  R. Lewis,et al.  Ciguatoxins: Cyclic Polyether Modulators of Voltage-gated Iion Channel Function , 2006, Marine Drugs.

[17]  L. D. Boada,et al.  Ciguatera Fish Poisoning, Canary Islands , 2005, Emerging infectious diseases.

[18]  M. Chinain,et al.  Biomonitoring of ciguatoxin exposure in mice using blood collection cards. , 2005, Toxicon : official journal of the International Society on Toxinology.

[19]  M. Dechraoui,et al.  Use of two detection methods to discriminate ciguatoxins from brevetoxins: application to great barracuda from Florida Keys. , 2005, Toxicon : official journal of the International Society on Toxinology.

[20]  M. Vieytes,et al.  Detection of sodium channel activators by a rapid fluorimetric microplate assay. , 2004, Chemical research in toxicology.

[21]  R. Lewis,et al.  Direct and indirect effects of ciguatoxin on guinea-pig atria and papillary muscles , 1986, Naunyn-Schmiedeberg's Archives of Pharmacology.

[22]  R. Lewis,et al.  Analysis of toxin profiles in three different fish species causing ciguatera fish poisoning in Guadeloupe, French West Indies , 2002, Food additives and contaminants.

[23]  R. Lewis,et al.  Multiple ciguatoxins present in Indian Ocean reef fish. , 2002, Toxicon : official journal of the International Society on Toxinology.

[24]  R. Lewis,et al.  Characterisation of multiple Caribbean ciguatoxins and congeners in individual specimens of horse-eye jack (Caranx latus) by high-performance liquid chromatography/mass spectrometry. , 2002, Toxicon : official journal of the International Society on Toxinology.

[25]  R. Lewis,et al.  Isolation and characterisation of Indian Ocean ciguatoxin. , 2002, Toxicon : official journal of the International Society on Toxinology.

[26]  M. Vieytes,et al.  A fluorimetric method based on changes in membrane potential for screening paralytic shellfish toxins in mussels. , 2001, Analytical biochemistry.

[27]  R. Lewis,et al.  The changing face of ciguatera. , 2001, Toxicon : official journal of the International Society on Toxinology.

[28]  T. Yasumoto The chemistry and biological function of natural marine toxins. , 2001, Chemical record.

[29]  R. Lewis,et al.  Ciguatera: recent advances but the risk remains. , 2000, International journal of food microbiology.

[30]  Sonia E. Guzma´n-Pe´rez and Douglas L. Park Ciguatera Toxins: Chemistry and Detection , 2000 .

[31]  K. Terao Ciguatera Toxins: Toxinology , 2000 .

[32]  M. Chinain,et al.  Structural Elucidation of Ciguatoxin Congeners by Fast-Atom Bombardment Tandem Mass Spectroscopy , 2000 .

[33]  L. Lehane,et al.  Ciguatera update , 2000, The Medical journal of Australia.

[34]  J. Vernoux,et al.  Hyperosmolar d-mannitol reverses the increased membrane excitability and the nodal swelling caused by Caribbean ciguatoxin-1 in single frog myelinated axons , 1999, Brain Research.

[35]  R. Lewis,et al.  HPLC/tandem electrospray mass spectrometry for the determination of Sub-ppb levels of Pacific and Caribbean ciguatoxins in crude extracts of fish. , 1999, Analytical chemistry.

[36]  M. Dechraoui,et al.  Ciguatoxins and brevetoxins, neurotoxic polyether compounds active on sodium channels. , 1999, Toxicon : official journal of the International Society on Toxinology.

[37]  R. Lewis,et al.  Structure of Caribbean Ciguatoxin Isolated from Caranx latus. , 1998 .

[38]  Y. Hokama,et al.  A simple membrane immunobead assay for detecting ciguatoxin and related polyethers from human ciguatera intoxication and natural reef fishes. , 1998, Journal of AOAC International.

[39]  M. Satake,et al.  Isolation and structures of new ciguatoxin analogs, 2,3-dihydroxyCTX3C and 51-hydroxyCTX3C, accumulated in tropical reef fish , 1998 .

[40]  Y. Hokama,et al.  Simplified solid-phase membrane immunobead assay (MIA) with monoclonal anti-ciguatoxin antibody (MAb-CTX) for detection of ciguatoxin and related polyether toxins. , 1998, Journal of natural toxins.

[41]  R. Lewis,et al.  Isolation and characterisation of Caribbean ciguatoxins from the horse-eye jack (Caranx latus). , 1997, Toxicon : official journal of the International Society on Toxinology.

[42]  J. Williamson,et al.  A Queensland family with ciguatera after eating coral trout , 1997, The Medical journal of Australia.

[43]  R. Lewis,et al.  Identification of Caribbean ciguatoxins as the cause of an outbreak of fish poisoning among U.S. soldiers in Haiti. , 1997, Toxicon.

[44]  M. Satake,et al.  Isolation and structure of ciguatoxin-4A, a new ciguatoxin precursor, from cultures of dinoflagellate Gambierdiscus toxicus and parrotfish Scarus gibbus. , 1996, Bioscience, biotechnology, and biochemistry.

[45]  J. Quod,et al.  Ciguatera in Réunion Island (SW Indian Ocean): epidemiology and clinical patterns. , 1996, Toxicon : official journal of the International Society on Toxinology.

[46]  T. Yasumoto,et al.  Morphological observations of diarrhea in mice caused by experimental ciguatoxicosis. , 1996, Toxicon : official journal of the International Society on Toxinology.

[47]  T. Yasumoto,et al.  Determinations of marine toxins in foods. , 1995, Journal of AOAC International.

[48]  R. Lewis,et al.  Purification and characterisation of large and small maitotoxins from cultured Gambierdiscus toxicus. , 1994, Natural toxins.

[49]  W. Lange,et al.  Ciguatera fish poisoning. , 1994, American family physician.

[50]  R. Lewis,et al.  Recovery of ciguatoxin from fish flesh. , 1993, Toxicon : official journal of the International Society on Toxinology.

[51]  M. Wekell,et al.  Tetrazolium-based cell bioassay for neurotoxins active on voltage-sensitive sodium channels: semiautomated assay for saxitoxins, brevetoxins, and ciguatoxins. , 1993, Analytical biochemistry.

[52]  J. Molgó,et al.  Ciguatoxin extracted from poisonous moray eels Gymnothorax javanicus triggers acetylcholine release from Torpedo cholinergic synaptosomes via reversed Na+ –Ca2+ exchange , 1993, Neuroscience Letters.

[53]  M. Satake,et al.  Gambierol: A New Toxic Polyether Compound Isolated from the Marine Dinoflagellate Gambierdiscus toxicus. , 1993 .

[54]  M. Satake,et al.  The structure of CTX3C, a ciguatoxin congener isolated from cultured Gambierdiscus toxicus , 1993 .

[55]  R. Lewis,et al.  Multiple ciguatoxins in the flesh of fish. , 1992, Toxicon : official journal of the International Society on Toxinology.

[56]  R. Lewis,et al.  Ciguatoxins are potent ichthyotoxins. , 1992, Toxicon : official journal of the International Society on Toxinology.

[57]  R. Lewis,et al.  Liquid chromatographic mass spectrometric methods for the determination of marine polyether toxins. , 1992, Bulletin de la Societe de pathologie exotique.

[58]  R. Norton,et al.  Purification and characterization of ciguatoxins from moray eel (Lycodontis javanicus, Muraenidae). , 1991, Toxicon : official journal of the International Society on Toxinology.

[59]  T. Yasumoto,et al.  Light and electron microscopic studies of pathologic changes induced in mice by ciguatoxin poisoning. , 1991, Toxicon : official journal of the International Society on Toxinology.

[60]  J. Osterloh,et al.  Normal fetal outcome after maternal ciguateric toxin exposure in the second trimester. , 1991, Journal of toxicology. Clinical toxicology.

[61]  R. Lewis,et al.  Strain dependent production of ciguatoxin precursors (gambiertoxins) by Gambierdiscus toxicus (Dinophyceae) in culture. , 1991, Toxicon : official journal of the International Society on Toxinology.

[62]  D. Blythe,et al.  Mother's milk turns toxic following fish feast. , 1990, JAMA.

[63]  T. Yasumoto,et al.  Structures and Configurations of Ciguatoxin from the Moray Eel Gymnothorax javanicus and Its Likely Precursor from the Dinoflagellate Gambierdiscus toxicus , 1990 .

[64]  T. Yasumoto,et al.  Structures of ciguatoxin and its congener , 1989 .

[65]  Y. Ohizumi,et al.  The mode of inotropic action of ciguatoxin on guinea‐pig cardiac muscle , 1988, British journal of pharmacology.

[66]  T. Iwashita,et al.  Some chemical properties of maitotoxin, a putative calcium channel agonist isolated from a marine dinoflagellate. , 1988, Journal of biochemistry.

[67]  R. Lewis Negative inotropic and arrhythmic effects of high doses of ciguatoxin on guinea-pig atria and papillary muscles. , 1988, Toxicon : official journal of the International Society on Toxinology.

[68]  M. Lazdunski,et al.  Ciguatoxin and brevetoxins share a common receptor site on the neuronal voltage‐dependent Na+ channel , 1987, FEBS letters.

[69]  Y. Hokama,et al.  ASSESSMENT OF A RAPID ENZYME IMMUNOASSAY STICK TEST FOR THE DETECTION OF CIGUATOXIN AND RELATED POLYETHER TOXINS IN FISH TISSUES , 1987 .

[70]  L. Yokochi,et al.  An Enzyme Immunoassay for the Detection of Ciguatoxin: And Competitive Inhibition by Related Natural Polyether Toxins , 1984 .

[71]  M. Lazdunski,et al.  Ciguatoxin is a novel type of Na+ channel toxin. , 1984, The Journal of biological chemistry.

[72]  Y. Shimizu Paralytic shellfish poisons. , 1984, Fortschritte der Chemie organischer Naturstoffe = Progress in the chemistry of organic natural products. Progres dans la chimie des substances organiques naturelles.

[73]  Y. Hokama,et al.  A rapid enzyme-immunoassay for the detection of ciguatoxin in contaminated fish tissues. , 1983, Toxicon : official journal of the International Society on Toxinology.

[74]  J. Pearn,et al.  Ciguatera and pregnancy , 1982, The Medical journal of Australia.

[75]  A. H. Banner,et al.  A radioimmunoassay for the detection of ciguatoxin. , 1977, Toxicon : official journal of the International Society on Toxinology.

[76]  S. K. Hong,et al.  Effect of ciguatoxin on sodium transport across the frog skin. , 1971, Toxicology and applied pharmacology.

[77]  A. H. Banner,et al.  Toxicity of the Surgeonfishes , 1971 .

[78]  M. Rayner,et al.  The Effect of Ciguatera Toxin on Aplysia Neurons 1 , 1970, Proceedings of the Society for Experimental Biology and Medicine. Society for Experimental Biology and Medicine.

[79]  R. Bagnis Ciguatera fish poisoning in French Polynesia. , 1967 .