Ciguatoxin

1111.31344

1111.31

2UKQ3B7696

White solid

241

2.5

1.38±0.1 g/cm3(Predicted)

Intravenous-rat LD50: 11 mg/kg; peritoneal-mouse LD50: 0.25 mg/kg

Flammable, decomposes toxic nitrogen oxide gas when burning

A complex toxic principle in bony fishes; has both fat- and water-soluble fractions. Ninhydrin test positive. It is a type of quaternary ammonium compound, and one fraction is said to be an irreversible anticholinesterase. The pharmacology is unknown.|MW: 1095.31. White amorphous solid. /CTX-2/|MW 1095.31. White amorphous solid. /CTX-3/

Treasury is low temperature, ventilated, dry; stored separately from food raw materials

SRP: Criteria for land treatment or burial (sanitary landfill) disposal practices are subject to significant revision. Prior to implementing land disposal of waste residue (including waste sludge), consult with environmental regulatory agencies for guidance on acceptable disposal practices.

WHO; Environ Health Criteria 37: Aquatic (Marine and Freshwater) Biotoxins (1984).[Available from, as of August 7, 2013: http://www.inchem.org/documents/ehc/ehc/ehc37.htm]

Marine pelagic cyanobacteria Trichodesmium are widespread in the New Caledonia (off the eastern coast of Australia) lagoon. Blooms of these Oscillatoriales are suspected to be a potential source of toxins in the ciguatera food chain and were previously reported to contain certain types of paralysing toxins. In the present study, toxicity experiments were conducted on lipid- and water-soluble extracts of freeze-dried samples of these cyanobacteria. Lipid-soluble fractions revealed a ciguatoxin-like activity in both in vivo (mouse bioassay) and in vitro (mouse neuroblastoma cells assay and receptor binding assay using tritiated brevetoxin-3) assays. The water-soluble fractions tested on mice exhibited neurotoxicity with paralytic symptoms. These toxicities have also been observed with benthic filamentous cyanobacteria within the Oscillatoriales order, also collected in New Caledonia. This study provides an unprecedented evidence of the toxicity of Trichodesmium species from the New Caledonia lagoon. This survey also demonstrates the possible role of these cyanobacteria in ciguatera fish poisoning.

most toxic

Mannitol (1 g/kg iv) is currently the treatment of choice for acute ciguatera, but confirmation of this treatment's apparent efficacy awaits further experimental or controlled clinical evidence. In mice, mannitol (1 g/kg iv) administered before or after ip ciguatoxin did not influence the signs of intoxication or the time to death. The effects of oral ciguatoxin differed from those following ip ciguatoxin, but again iv mannitol provided no detectable benefit. Development of hypothermia was rapid in mice receiving ip or oral ciguatoxin and was unaffected by iv mannitol. A sublethal ip dose of ciguatoxin initially retarded (day 0-4) but then accelerated (day 4-12) the growth of mice. Mannitol (iv) had no influence on these effects of ciguatoxin on the growth of mice. Ciguatoxin inhibited responses of isolated diaphragms to nerve stimulation (ED50 = 9 x 10(-11) M), while directly stimulated diaphragms were inhibited by five-fold higher concentrations. Mannitol (50 mM) added to the organ bath did not influence the ciguatoxin-induced inhibition of diaphragm responses to nerve stimulation in vitro. Responses of isolated diaphragm to nerve stimulation were normal in preparations removed from ciguatoxin-treated mice displaying pronounced dyspnoea (gasping). However, responses to nerve stimulation were reduced in preparations removed from mice immediately following death from ciguatoxin. Mannitol (iv) partially protected the phrenic nerve-diaphragm from this effect of ciguatoxin in vivo. /The authors/ conclude that the lethal effects of ciguatoxin in mice probably stem from a central action, and suggest that species differences may account for the absence of any marked beneficial effect of iv mannitol in the mouse model for ciguatera in humans.|Electrophysiological studies were performed on the ventral tail nerve of adult rats following intraperitoneal injection of a crude extract of ciguatoxin from known toxic fish flesh. Ciguatoxin induced significant slowing of both mixed and motor nerve conduction velocities and also significant reductions in both motor and mixed nerve amplitudes. Both absolute and supernormal periods were significantly prolonged together with an increase in the magnitude of the supernormal response. These electrophysiological disturbances were modified or blocked by intraperitoneal lidocaine. These findings suggest that lidocaine may have a potential therapeutic application in the treatment of the neurological disturbance in acute ciguatera poisoning in humans.|This report describes the action of ciguatoxin-1, the major ciguatoxin present in fishes that cause ciguatera, on the contractile activity of human cardiac musculature. Ciguatoxin-1 caused a large, sustained and concentration-dependent positive inotropy in human atrial trabeculae that were obtained during coronary artery bypass surgery from otherwise healthy hearts. Atenolol (a beta 1-adrenoceptor selective antagonist without local anaesthetic-type activity) or low concentrations of tetrodotoxin abolished the positive inotropy caused by ciguatoxin-1, indicating that ciguatoxin-1 stimulated neural elements present in this tissue to release noradrenaline. The positive inotropic action of ciguatoxin-1 did not stem from a significant direct action on myocardial voltage-dependent sodium channels, nor did it stem from significant alpha 1- or beta 2-adrenoreceptor stimulation. Ciguatoxin-1 caused positive inotropy in preparations stimulated at between 0.02 and 2.0 Hz. Mannitol, currently the treatment of choice for ciguatera, did not significantly reverse the positive inotropy induced by ciguatoxin-1 in human atrial trabeculae.|Ciguatoxin-1b, the major toxin involved in ciguatera fish poisoning, and D-mannitol were examined on frog nodes of Ranvier using confocal laser scanning microscopy and conventional current and voltage-clamp techniques. During the action of 10 nM ciguatoxin-1b, an increase in nodal volume was observed as determined by digital image processing and three-dimensional reconstruction of axons. The increase was prevented by blocking Na + channels with tetrodotoxin. Ciguatoxin-1b (10 nM) induced high frequency action potential discharges up to 70-100 Hz. Analysis of Na+ current revealed that the toxin modified a current fraction which was activated at resting membrane potential and failed to inactivate. Increasing the osmolality of the external solution by about 50% with D-mannitol restored the nodal volume to its control value and suppressed spontaneous action potentials. In addition, D-mannitol affected unmodified and ciguatoxin-1b-treated Na+ currents in a similar manner causing a reduction of maximum conductance, negative shifts of current reversal potential and modification of the voltage-dependence of current activation and inactivation. In conclusion, ciguatoxin-1b induced a tetrodotoxin-sensitive swelling of nodes of Ranvier and selectively affected the Na+ current of myelinated axons.|For more Interactions (Complete) data for CIGUATOXIN (8 total), please visit the HSDB record page.

LD50 Mouse ip 0.25 ug/kg

/AQUATIC SPECIES/ Ciguatoxins are lipophilic polyether toxins which concentrate in the viscera and flesh of coral reef associated finfish. In this study, /the investigators/ quantify the adverse effects of ciguatoxin on fish embryos by microinjection into the egg yolk of medaka (Oryzias latipis) embryos. Embryos microinjected with 0.1-0.9 pg/egg (ppb) of ciguatoxin exhibit cardiovascular, muscular, and skeletal abnormalities and those injected with higher levels (1.0-9.0 pg/egg) exhibit significantly reduced hatching success. The sensitivity of embryonic fish to direct oocyte exposure indicates that maternal transfer of low levels of ciguatoxin may represent an unrecognized threat to the reproductive success of reef fish and a previously undetected ecological consequence of proliferation of ciguatoxin-producing algae in reef systems increasingly impacted by human perturbations.|/AQUATIC SPECIES/ The absolute refractory period, relative refractory period, and the duration and magnitude of the supernormal period were measured after incubation of fish nerves with ciguatoxin and other channel modifying compounds, tetrodotoxin, veratridine, verapamil, and lignocaine. In vitro electrophysiological studies were carried out on the lateral line nerve of the whiting, Sillago ciliata Cuvier. Electrophysiological changes in fish nerves after exposure to ciguatoxin (0.3 MU/mL) and veratridine (1 x 10-5 M) are similar to changes that occur in mammalian nerves and include an increase in the absolute refractory period, the relative refractory period, and the magnitude and duration of supernormality. The effects of ciguatoxin (0.3 MU/mL) in fish nerves were antagonised by tetrodotoxin (5 x 10-10 M), verapamil (5 x 10-7 M), and lignocaine (1 x 10-5 g/mL). The nerves of Sillago ciliata used in this study responded to ciguatoxin and its antagonists in a similar manner to mammalian nerves, suggesting that these teleost nerves have no specific electrophysiological mechanism to cope with this toxin.

Potent sodium channel activators found in a wide variety of fish, the toxins were ultimately traced to a dinoflagellate Gambierdiscus spp.|A dinoflagellate, Gambierdiscus toxicus, has been identified as the source of ciguatoxin and maitotoxin. G. toxicus is an armoured dinoflagellate with two flagella, living around coral reefs, closely attached to macroalgae, such as Turbinaria ornata, Amphiroa sp., and Jania sp. Ciguatoxin and maitotoxin have been isolated from the biodetritus layer on coral reefs, from G. toxicus collected from sea water, and from axenic cultures of G. toxicus. ... Strains of G. toxicus, able to produce ciguatoxin and maitotoxin, have repeatedly been isolated from macroalgae such as Halimeda sp., Penicillus sp., Acetabularia sp. and Gracilaria sp., and from coral reef off the coast of Florida. These findings elucidate the origin of toxicity of Florida barracuda (Sphyranea barracuda), a fish species often associated with cases of ciguatera in US(1).|In general, ciguatoxin-containing species are limited to fish that feed on algae and the detritus of coral reefs, particularly the surgeon-fish (Ctenochaetus striatus), parrot-fish (Scarus gibbus), and the larger reef carnivores that prey on these herbivores. Thus, the larger carnivores such as moray eels, snappers, groupers, carrangs, Spanish mackerels, emperors, certain in-shore tunas, and barracuda are most toxic(1).|Natural disturbances of the coral reefs, such as hurricanes and storms ... provide conditions for growth of the macroalgae to which Gambierdiscus toxicus cells are attached, resulting in increased dinoflagellate populations. These disturbances, which cause increased numbers of ciguatoxic fish and increased toxin levels in the affected fish resulting in increased incidence rates of ciguatera, may have long-lasting effects, up to 10 - 15 years after the disturbance took place.

Man-made disturbances, such as blasting of reefs, crashing of ship anchors, and building of piers or wharfs, provide conditions for growth of the macroalgae to which Gambierdiscus toxicus cells are attached, resulting in increased dinoflagellate populations. These disturbances, which cause increased numbers of ciguatoxin-containing fish and increased toxin levels in the affected fish resulting in increased incidence rates of ciguatera, may have long-lasting effects, up to 10 - 15 years after the disturbance took place(1).

Ciguatoxins are potent sodium channel activators found in a wide variety of fish; the toxins were ultimately traced to a dinoflagellate Gambierdiscus spp. Ciguatoxin has been isolated from the biodetritus layer of coral reefs, from the dinoflagellate Gambierdiscus toxicus collected from seawater, and from axenic cultures of G. toxicus. Natural disturbances of the coral reefs, such as hurricanes and storms as well as man-made disturbances, such as blasting of reefs, crashing of ship anchors, and building of piers or wharfs, also provide conditions for growth of the macroalgae to which Gambierdiscus toxicus cells are attached, resulting in increased dinoflagellate populations. These disturbances, which cause increased numbers of ciguatoxic fish and increased toxin levels in the affected fish resulting in increased incidence rates of ciguatera, may have long-lasting effects, up to 10 - 15 years after the disturbance took place. This family of lipid soluble polyether toxins are responsible for ciguatera food poisoning. In general, ciguatoxin-containingc species are limited to fish that feed on algae and the detritus of coral reefs, particularly the surgeon-fish (Ctenochaetus striatus), parrot-fish (Scarus gibbus), and the larger reef carnivores that prey on these herbivores. Thus, the larger carnivores such as moray eels, snappers, groupers, carrangs, Spanish mackerels, emperors, certain in-shore tunas, and barracuda are most toxic. Structural variations are associated with the oceanic region from which the dinoflagellate originates. The recent detection of the CTX-producing tropical genus Gambierdiscus in the eastern Atlantic Ocean of the northern hemisphere and in the Mediterranean Sea, as well as the confirmation of CFP in the Canary Islands and possibly in Madeira, has raised the question of the possible contribution of climate change to the distribution of toxin-producing microalgae and ciguateric fish. The general population may be exposed to ciguatoxin via ingestion of certain infected fish species. (SRC)

Aim: To characterize the risks of Ciguatera Fish Poisoning and to consider whether dietary recommendations need refining in view of those risks. Background - Regular fish consumption has been recommended for both primary and secondary prevention of cardiovascular disease. Ciguatera Fish Poisoning (CFP) is the most frequently reported intoxication resulting from fish consumption in Australia. The ciguatoxin are produced by the unicellular Gambierdiscus toxicus, a component of plankton typically associated with bleached coral reefs. The clinical syndrome included gastrointestinal and prominent neurological symptoms. Regular fish consumers may accumulate a subclinical toxin level, and may be at increased risk of developing clinical and/or recurrent CFP. Method - Medline, USDA, AFFA, CSIRO and AHA databases and websites search. Results - Cold water fish species do not constitute a CFP risk and have a favorable long chain n-3 fatty acid profile, (Tuna, Atlantic Salmon, Blue-eye and Sardines). Warm water mackerels and reef fish, particularly Coral Trout pose the most significant CFP risk. Conclusions - Recommendations regarding fish intake ought to include consideration of CFP as risks may outweigh benefits for some fish species.

Ciguatera fish poisoning (CFP) occurs mainly when humans ingest finfish contaminated with cigatoxins (CTXs). ... Reports of CFP cases in European hospitals have been described in several countries, and are mostly due to travel to CFP endemic areas. Additionally, the recent detection of the CTX-producing tropical genus Gambierdiscus in the eastern Atlantic Ocean of the northern hemisphere and in the Mediterranean Sea, as well as the confirmation of CFP in the Canary Islands and possibly in Madeira, constitute other reasons to study the onset of CFP in Europe. The question of the possible contribution of climate change to the distribution of toxin-producing microalgae and ciguateric fish is raised. The impact of ciguatera onset on European Union (EU) policies will be discussed with respect to EU regulations on marine toxins in seafood. Critical analysis and availability of methodologies for CTX determination is required for a rapid response to suspected CFP cases and to conduct sound CFP risk analysis.

Substances which, when ingested, inhaled, or absorbed, or when applied to, injected into, or developed within the body in relatively small amounts may, by their chemical action, cause damage to structure or disturbance of function. (From Dorland, 27th ed) (See all compounds classified as Poisons.)

In this study, /the researchers/ determined the toxicokinetic parameters of the Pacific ciguatoxin P-CTX-1 in rats after an intravenous (iv) dose of 0.13 ng P-CTX-1 per g of body weight. The ciguatoxin activity was assessed over time in blood using the sensitive functional Neuro2a assay. The data were analyzed with a two-compartmental model. After exposure, the ciguatoxin activity exhibited a rapid (alpha half-life of 6 min) and extensive distribution into tissues (apparent steady state volume of distribution of 7.8 L). Ciguatoxin elimination from blood was slower with a beta half-life estimated at 35.5 hr. The toxicokinetic parameters determined from this study were compared to data previously obtained after oral and intraperitoneal exposure of rats to 0.26 ng P-CTX-1 per g of body weight. Maximal bioavailability was determined by the area under the concentration curve, and was used to calculate the absolute P-CTX-1 bioavailabilities for oral and intraperitoneal routes of exposures of 39% and 75%, respectively.|Ciguatoxin accumulates in all fish tissues, especially the liver and viscera, of "at risk" species.|Ciguatera in humans is typically caused by the consumption of reef fish that have accumulated Ciguatoxins (CTXs) in their flesh. Over a six month period, /the researchers/ captured 38 wild adult great barracuda (Sphyraena barracuda), a species commonly associated with ciguatera in The Bahamas. /The researchers/ sampled three tissues (i.e., muscle, liver, and blood) and analysed them for the presence of ciguatoxins using a functional in vitro N2A bioassay. Detectable concentrations of ciguatoxins found in the three tissue types ranged from 2.51 to 211.74pg C-CTX-1 equivalents/g. Blood and liver toxin concentrations were positively correlated (P=0.86, P=0.003), indicating that ... blood sampling provides a non-lethal method of detecting ciguatoxin in wild fish. Non-lethal blood sampling also presents opportunities to couple this approach with biotelemetry and biologging techniques that enable the study of fish distribution and movement. To demonstrate the potential for linking ciguatoxin occurrence with barracuda spatial ecology, /the researchers/ also present a proof-of-concept case study where blood samples were obtained from 20 fish before releasing them with acoustic transmitters and tracking them in the coastal waters using a fixed acoustic telemetry array covering 44km(2). Fish that tested positive for CTX may have smaller home ranges than non-toxic fish (median distance travelled, U=2.21, P=0.03). Results presented from this study may help identify high risk areas and source-sink dynamics of toxins, potentially reducing the incidence and human health risk of ciguatera fish poisoning. Moreover, development of the non-lethal sampling approach and measurement of ciguatera from blood provide future opportunities to understand the mechanistic relationship between toxins and the spatial ecology of a broad range of marine fish species.|Ciguatoxins are also transmitted in breast milk and are able to cross the placenta and affect the fetus.|For more Absorption, Distribution and Excretion (Complete) data for CIGUATOXIN (6 total), please visit the HSDB record page.

In this study /the researchers/ determined the toxicokinetic parameters of the Pacific ciguatoxin P-CTX-1 in rats after an intravenous (iv) dose of 0.13 ng P-CTX-1 per g of body weight. ... After exposure, the ciguatoxin activity exhibited a rapid (alpha half-life of 6 min) and extensive distribution into tissues (apparent steady state volume of distribution of 7.8 L). Ciguatoxin elimination from blood was slower with a beta half-life estimated at 35.5 hr. ...

The pharmacological action of ciguatoxin is related to its direct effects on excitable membranes rather than to its antichlolinesterase properties. Ciguatoxin has a potent depolarising action due to a selective increase in sodium permeability in the nerve cells and striated muscle, which can be counteracted by calcium ions. The effect of ciguatoxin on smooth muscle can be explained by a potent releasing action of the toxin on endogenous norepinephrine from adrenergic nerve terminals and a potentiating effect on the postsynaptic membrane.|Agents acting on signaling systems for neurotransmitters and causing dysregulation of the momentary activity of electrically excitable cells such as neurons and muscle cells: Ciguatoxin interferes with the voltage-gated sodium ion channel causing neuronal activation/convulsions. /from table/|Ciguatoxins are potent, lipophilic sodium channel activator toxins which bind to the voltage sensitive (site 5) sodium channel on the cell membranes of all excitable tissues.|Ciguatoxins and brevetoxins, through different vectors, are responsible for human intoxications characterized mainly by neurological disturbances. The molecular target of these families of lipid-soluble cyclic polyethers is the voltage-gated sodium channel, a fundamental transmembrane protein involved in cellular excitability. The different toxins share a common binding site (the receptor-site 5) located on the alpha sub-unit of this neuronal transmembrane protein. Electrophysiological studies of the mode of action of ciguatoxins and brevetoxins identify these toxins as specific sodium channel activators. Indeed, during the action of these phycotoxins, sodium channels remain permanently opened, at the resting membrane potential, which produces a continuous entry of sodium ions in most excitable cells. Such a sodium entry has various consequences on sodium-dependent physiological mechanisms, consisting in a membrane depolarization which, in turn, causes spontaneous and/or repetitive action potential discharges and thereby increases membrane excitability. These neuronal discharges may be transient or continuous according to the preparation and the toxin tested. The increase in membrane excitability during the action of ciguatoxins and brevetoxins is responsible for the different effects exerted by these toxins on various chemical synapses and secretory cells. Another consequence of the continuous entry of sodium ions into cells was revealed. ... These phycotoxins cause a marked increase in the volume of nodes of Ranvier of myelinated nerve fibres, motor nerve terminals innervating skeletal muscle and perisynaptic non-myelinating Schwann cell somata. This increase could be reversed by hyperosmotic external solutions and completely prevented by the blockade of voltage-gated sodium channels.|For more Mechanism of Action (Complete) data for CIGUATOXIN (14 total), please visit the HSDB record page.

To assess the effectiveness of IV Mannitol treatment for Ciguatera Poisoning, 35 patients were treated from the Miami-Caribbean area with symptoms of acute and chronic Ciguatera Poisoning. Information was collected on demographics, fish type and location, timing and type of symptoms, and response to treatment. IV Mannitol ... given within 48 hours dramatically decreased the acute morbidity of Ciguatera Poisoning without serious side effects. Treatment also appears to be safe and effective in chronic cases up to eight weeks from ingestion of toxic fish.|/EXPERIMENTAL/ Ciguatera, the most common form of non-bacterial ichthyosarcotoxism, is caused by consumption of fish that have bioaccumulated the polyether sodium channel activator ciguatoxin. The neurological symptoms of ciguatera include distressing, often persistent sensory disturbances such as paraesthesias and the pathognomonic symptom of cold allodynia. /The researchers/ show that intracutaneous administration of ciguatoxin in humans elicits a pronounced axon-reflex flare and replicates cold allodynia. To identify compounds able to inhibit ciguatoxin-induced /voltage-gated sodium channel/ (Nav) responses, /the researchers/ developed a novel in vitro ciguatoxin assay using the human neuroblastoma cell line SH-SY5Y. Pharmacological characterisation of this assay demonstrated a major contribution of Nav1.2 and Nav1.3, but not Nav1.7, to ciguatoxin-induced Ca2+ responses. Clinically available Nav inhibitors, as well as the Kv7 agonist flupirtine, inhibited tetrodotoxin-sensitive ciguatoxin-evoked responses. To establish their in vivo efficacy, /the researchers/ used a novel animal model of ciguatoxin-induced cold allodynia. However, differences in the efficacy of these compounds to reverse ciguatoxin-induced cold allodynia did not correlate with their potency to inhibit ciguatoxin-induced responses in SH-SY5Y cells or at heterologously expressed Nav1.3, Nav1.6, Nav1.7 or Nav1.8, indicating cold allodynia might be more complex than simple activation of Nav channels. These findings highlight the need for suitable animal models to guide the empiric choice of analgesics, and suggest that lamotrigine and flupirtine could be potentially useful for the treatment of ciguatera.|Treatment depends on early diagnosis and the early administration of intravenous mannitol. The early identification of the neurological features in sentinel patients has the potential to reduce the number of secondary cases in cluster outbreaks.|/SRP:/ Immediate first aid: Ensure that adequate decontamination has been carried out. If patient is not breathing, start artificial respiration, preferably with a demand valve resuscitator, bag-valve-mask device, or pocket mask, as trained. Perform CPR if necessary. Immediately flush contaminated eyes with gently flowing water. Do not induce vomiting. If vomiting occurs, lean patient forward or place on the left side (head-down position, if possible) to maintain an open airway and prevent aspiration. Keep patient quiet and maintain normal body temperature. Obtain medical attention. /Poisons A and B/|For more Antidote and Emergency Treatment (Complete) data for CIGUATOXIN (7 total), please visit the HSDB record page.

/SIGNS AND SYMPTOMS/ The phenomenon of sensitization has been observed where persons who previously were intoxicated with ciguatoxin may suffer a recurrence of typical ciguatera symptoms after eating fish that do not cause symptoms in other persons. Such sensitization can occur many months or even years after an attack of ciguatera fish poisoning.|/SIGNS AND SYMPTOMS/ Neurological disturbances usually resolve within weeks of onset, although some symptoms may persist for months or even years. Symptoms such as pruritus, arthralgia and fatigue can also persist for months or years. Analysis of ciguatoxins in blood samples suggests that the toxin can be stored in adipose tissue and that symptoms may recur during periods of stress, such as exercise, weight loss, or excessive alcohol consumption. Sensitivity to alcohol may also persist for years after the first attack.|/SIGNS AND SYMPTOMS/ The clinical picture is quite variable. Typically, symptoms occur within 1-6 hr of ingestion of toxic fish. Initial symptoms usually include nausea, malaise, and numbness and tingling of the lips, tongue, and throat. Patients may later develop some or all of the following signs and symptoms: vomiting, abdominal cramps, diarrhea, paraesthesia of the extremities, itching myalgia, and arthralgia. In more severe cases, ataxia, weakness, blurred vision, insomnia, sinus bradycardia, dysrhythmias, and hypotension may develop. A symptom that particularly suggests the diagnosis is alternating sensations of cold and hot. The duration of illness is variable. Most of the patients recover within 3 days, but malaise, paraesthesia, pruritus, and ataxia may persist for weeks or even years in severe cases. Patients repeatedly poisoned by ciguatoxic fish may develop a resurgence of ciguatera symptoms even after eating fish containing little or no detectable toxin.|/SIGNS AND SYMPTOMS/ The common clinical manifestations are a combination of gastrointestinal and neurologic symptoms. Severe poisoning may be associated with seizures and respiratory paralysis.|For more Human Toxicity Excerpts (Complete) data for CIGUATOXIN (30 total), please visit the HSDB record page.

Ciguatoxin

Ciguatoxin and maitotoxin have been isolated from the biodetritus layer of coral reefs, from the dinoflagellate Gambierdiscus toxicus collected from seawater, and from axenic cultures of G. toxicus.|Family of lipid soluble polyether toxins responsible for ciguatera food poisoning; structural variations are associated with the oceanic region from which the dinoflagellate originates. /Ciguatoxins/|Toxin profiles of representative ciguatera species caught at different locations of Japan were investigated in fish flesh by high-performance liquid chromatography tandem mass spectrometry (LC-MS/MS) analysis. Identification and quantification of 16 toxins were facilitated by the use of 14 reference toxins prepared by either synthesis or isolation from natural sources and the previous LC-MS data thereof. Sodium adduct ions [M + Na]+ were used as parent and product ions. Distinct regional differences were unveiled: ciguatoxin-1B type toxins were found in snappers and groupers from Okinawa, ciguatoxin-3C type toxins were found in a spotted knifejaw, Oplegnathus punctatus, from Miyazaki located 730 km north of Okinawa, and both types of toxins were found in a red snapper, Lutjanus bohar, from Minamitorishima (Marcus) Island. Twelve toxins were identified in a dinoflagellate, Gambierdiscus toxicus, collected as the primary toxin source in French Polynesia. Occurrence of M-seco-toxins in fish and oxidized toxins in the dinoflagellate was confirmed for the first time. The present LC-MS/MS method is rapid, specific, and accurate. It not only outperforms the currently employed mouse bioassays but also enables the study of the toxin dynamics during the food chain transmission.

For ciguatoxin, a mouse injection test ... The method consists of injecting serially-diluted semipurified toxin extracts into mice and observing the mortality ratio for 24 hr. The results are obtained as mouse units, and one mouse unit is defined as the amount of toxin that kills a mouse (20 g body weight) in 24 hr. The method does not distinguish between ciguatoxin and scaritoxin.|A bioassay for ciguatoxin in fish has been developed on the basis of feeding cats or mongooses a ration containing 100 g of the fish to be tested per kg ration. The cat is less satisfactory, because it may regurgitate part of the test meal. Test animals were observed for 48 hr, with the response rated from 0 (no response) to 5 (death within 48 hr). ... A bioassay using mosquitoes (Aedes aegypti) has been developed. The procedure involves intrathoracic injection in mosquitoes of serially-dilated extract from fish, and the toxicity of the fish is expressed as mosquito LD50. A good correlation between the mosquito bioassay and the mouse bioassay was observed. All the tests described above appear to be non-specific and only semiquantitative at best.|A radioimmunoassay for ciguatoxin has been developed, using antibodies produced against a conjugate of human serum albumin and ciguatoxin isolated from toxic moray eel. Results of the assay were correlated with those of the assays on mongoose, mouse, and guinea-pig atrium. All the three assay procedures showed good correlation when ciguatoxin was present in fish tissues in high concentrations.|Ciguatera fish poisoning (CFP) is a food intoxication caused by exposure to ciguatoxins (CTXs) in coral reef fish. Rapid analytical methods have been developed recently to quantify Pacific-CTX-1 (P-CTX-1) in fish muscle, but it is destructive and can cause harm to valuable live coral reef fish. Also fish muscle extract was complex making CTX quantification challenging. Not only P-CTX-1, but also P-CTX-2 and P-CTX-3 could be present in fish, contributing to ciguatoxicity. Therefore, an analytical method for simultaneous quantification of P-CTX-1, P-CTX-2, and P-CTX-3 in whole blood of marketed coral reef fish using sonication, solid-phase extraction (SPE), and liquid chromatography tandem mass spectrometry (LC-MS/MS) was developed. The optimized method gave acceptable recoveries of P-CTXs (74-103%) in fish blood. Matrix effects (6-26%) in blood extracts were found to be significantly reduced compared with those in muscle extracts (suppressed by 34-75% as reported in other studies), thereby minimizing potential for false negative results. The target P-CTXs were detectable in whole blood from four coral reef fish species collected in a CFP-endemic region. Similar trends in total P-CTX levels and patterns of P-CTX composition profiles in blood and muscle of these fish were observed, suggesting a relationship between blood and muscle levels of P-CTXs. This optimized method provides an essential tool for studies of P-CTX pharmacokinetics and pharmacodynamics in fish, which are needed for establishing the use of fish blood as a reliable sample for the assessment and control of CFP.|Ciguatera is a significant food-borne disease caused by potent polyether toxins (ciguatoxins) which accumulate in the flesh of ciguateric reef fish at risk levels > 0.1 ppb for Pacific ciguatoxins. Research on ciguatera has been severely hindered by the lack of analytical methods that detect and characterize low levels of ciguatoxin in crude extracts of fish. Here we report a new procedure for ciguatoxin analysis based on gradient reversed-phase HPLC/tandem mass spectrometry (HPLC/MS/MS). The method gave a linear response to pure Pacific and Caribbean ciguatoxins (P-CTX-1 and C-CTX-1) and the structurally related brevetoxin (PbTx-2) spiked into crude extracts of fish. Levels equivalent to 40 ppt P-CTX-1, 100 ppt C-CTX-1, and 200 ppt PbTx-2 in fish flesh could be detected by HPLC/MS/MS. Using P-CTX-1 as an internal standard, the analysis of extracts of 30 ciguateric fish from the Caribbean Sea (8 toxic, 12 borderline, and 10 nontoxic by mouse bioassay) confirmed the reliability of the method and allowed an estimated risk level of > 0.25 ppb C-CTX-1 to be established. HPLC/MS/MS provides a sensitive analytical approach, not previously available, for the determination of Pacific and Caribbean ciguatoxins at sub-ppb levels in fish flesh.