Acute paralysis after seafood ingestion

Fernández-Fígares, M.; Fernández, Villar; Postigo, M.; Feron, Pascale

doi:10.1016/j.neucli.2013.08.013

Cited by 6 publications

(5 citation statements)

References 13 publications

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“…The presence of TTX and regulated marine toxins such as the paralytic shellfish toxins saxitoxins in pufferfish from the Atlantic has been recently reported [14]. Furthermore, recent reports have described the presence of this potent neurotoxin in mollusks and gastropods worldwide [3,5,6,8,11,28,32] raising growing concerns about TTX regulation in fish and mollusks [10,20]. Recently EFSA reported a mean human exposure level for TTX after clams, mussels, or oysters ingestion of 0.02, 0.03, and 0.09 µ g/kg b.w., respectively, whereas for the other bivalves the level of acute exposure to TTX was zero [20].…”

Section: Discussionmentioning

confidence: 99%

“…In this case, both TTX and its analogue 5,6,11-trideoxyTTX were identified in the digestive tract of the shellfish and in the urine and plasma of the intoxicated patient. As a result of the ingestion of the trumpet shellfish, the patient suffered general paralysis and required mechanical ventilation during 52 h after the intoxication, recovering 72 h after hospital admission [6,7]. In fact, recently, the presence of TTX in juvenile pufferfish Lagocephalus sceleratus, previously considered non-toxic, has been reported in European coasts, mainly in the Mediterranean Sea [2,8] with some of the tissues containing TTXs amounts that reached 2 mg/kg [9].…”

Section: Introductionmentioning

confidence: 99%

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Oral Chronic Toxicity of the Safe Tetrodotoxin Dose Proposed by the European Food Safety Authority and Its Additive Effect with Saxitoxin

Boente-Juncal

Otero

Rodríguez³

et al. 2020

Toxins

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Tetrodotoxin (TTX) is a potent natural toxin causative of human food intoxications that shares its mechanism of action with the paralytic shellfish toxin saxitoxin (STX). Both toxins act as potent blockers of voltage-gated sodium channels. Although human intoxications by TTX were initially described in Japan, nowadays increasing concern about the regulation of this toxin in Europe has emerged due to its detection in fish and mollusks captured in European waters. Currently, TTX is only regularly monitored in Dutch fishery products. However, the European Food Safety Authority (EFSA) has established a safety level of 44 µg/kg TTX as the amount of toxin that did not cause adverse effects in humans. This level was extrapolated considering initial data on its acute oral toxicity and EFSA remarked the need for chronic toxicity studies to further reduce the uncertainty of future toxin regulations. Thus, in this work, we evaluated the oral chronic toxicity of TTX using the safety levels initially recommended by EFSA in order to exclude potential human health risks associated with the worldwide expanding presence of TTX. Using internationally recommended guidelines for the assessment of oral chronic toxicity, the data provided here support the proposed safety level for TTX as low enough to prevent human adverse effects of TTX even after chronic daily exposure to the toxin. However, the combination of TTX with STX at doses above the maximal exposure level of 5.3 µg/kg body weight derived by EFSA increased the lethality of TTX, thus confirming that both TTX and paralytic shellfish toxins should be taken into account to assess human health risks.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Oral Chronic Toxicity of the Safe Tetrodotoxin Dose Proposed by the European Food Safety Authority and Its Additive Effect with Saxitoxin

Boente-Juncal

Otero

Rodríguez³

et al. 2020

Toxins

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“…The first report of poisoning due to TTX in Europe is from Malaga, Spain. A 49‐year‐old man consumed trumpet clam ( Charonia lampas sualiae ) that had been caught off the southern coast of Portugal and sold in a local fish market (Rodriguez et al., ; Fernandez‐Ortega et al., ; Fernández‐Fígares et al., ). He boiled it for 45 min, then ate the ventral portion and a few minutes later started to feel perioral numbness, which extended to both arms, followed by abdominal pain, nausea and vomiting.…”

Section: Assessmentmentioning

confidence: 99%

Risks for public health related to the presence of tetrodotoxin (TTX) and TTX analogues in marine bivalves and gastropods

Knutsen¹,

Alexander²,

Barregård³

et al. 2017

EFS2

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Tetrodotoxin (TTX) and its analogues are produced by marine bacteria and have been detected in marine bivalves and gastropods from European waters. The European Commission asked EFSA for a scientific opinion on the risks to public health related to the presence of TTX and TTX analogues in marine bivalves and gastropods. The Panel on Contaminants in the Food Chain reviewed the available literature but did not find support for the minimum lethal dose for humans of 2 mg, mentioned in various reviews. Some human case reports describe serious effects at a dose of 0.2 mg, corresponding to 4 lg/kg body weight (bw). However, the uncertainties on the actual exposure in the studies preclude their use for derivation of an acute reference dose (ARfD). Instead, a group ARfD of 0.25 lg/kg bw, applying to TTX and its analogues, was derived based on a TTX dose of 25 lg/kg bw at which no apathy was observed in an acute oral study with mice, applying a standard uncertainty factor of 100. Estimated relative potencies for analogues are lower than that of TTX but are associated with a high degree of uncertainty. Based on the occurrence data submitted to EFSA and reported consumption days only, average and P95 exposures of 0.00-0.09 and 0.00-0.03 lg/kg bw, respectively, were calculated. Using a large portion size of 400 g bivalves and P95 occurrence levels of TTX, with exception of oysters, the exposure was below the group ARfD in all consumer groups. A concentration below 44 lg TTX equivalents/kg shellfish meat, based on a large portion size of 400 g, was considered not to result in adverse effects in humans. Liquid chromatography with tandem mass spectroscopy (LC-MS/MS) methods are the most suitable for identification and quantification of TTX and its analogues, with LOQs between 1 and 25 lg/kg.

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“…As a low dosage of TTX can barely cross the blood–brain barrier [ 20 , 21 ], in a certain dose range, TTX predominantly affects the conduction of the peripheral nervous system and skeletal muscles via the blocking of Na v 1.4, Na v 1.6 and Na v 1.7 [ 19 ]; thus, the influence of TTX on the peripheral nervous system and skeletal muscles requires further investigation. Previous studies showed a trend for self-healing in TTX poisoning [ 22 , 23 , 24 , 25 ], but the process lacked detailed descriptions. Therefore, we established TTX poisoning models via i.m.…”

Section: Discussionmentioning

confidence: 99%

Acute Toxic Effects of Tetrodotoxin in Mice via Intramuscular Injection and Oral Gavage

Wang¹,

Zhang²,

Song³

et al. 2023

Toxins

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Tetrodotoxin (TTX) is a highly fatal marine biotoxin. Constantly increasing intoxications and the lack of specific antitoxic drugs in clinical applications highlight the need for further research into the toxic effects of TTX. Current reports on poisoning cases and the TTX toxicity mechanism suggest that the blocking of voltage-gated sodium channels (VGSCs) by TTX is probably reversible, but direct evidence of this is lacking, as far as we are aware. This study explored the acute toxic effects of TTX at sub-lethal doses via different routes, analyzing variations in muscle strength and TTX concentration in the blood in mice. We found that the loss of muscle strength in mice caused by TTX was dose-dependent and reversible, and the death time and muscle strength variations after oral gavage with TTX appeared to occur later and were more variable than those after intramuscular injection. In conclusion, we systematically compared the acute toxic effects of TTX for two different administration routes at sub-lethal doses, directly verifying the reversible reaction of TTX blocking VGSCs and speculating that averting a complete block of VGSCs by TTX could be an effective strategy for preventing death from TTX poisoning. This work may provide data for the diagnosis and treatment of TTX poisoning.

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Acute paralysis after seafood ingestion

Cited by 6 publications

References 13 publications

Oral Chronic Toxicity of the Safe Tetrodotoxin Dose Proposed by the European Food Safety Authority and Its Additive Effect with Saxitoxin

Oral Chronic Toxicity of the Safe Tetrodotoxin Dose Proposed by the European Food Safety Authority and Its Additive Effect with Saxitoxin

Risks for public health related to the presence of tetrodotoxin (TTX) and TTX analogues in marine bivalves and gastropods

Acute Toxic Effects of Tetrodotoxin in Mice via Intramuscular Injection and Oral Gavage

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