What Is Tetrodotoxin Poisoning?

  • Deepika RanaBachelor of Dental Surgery(BDS), Dentistry , H.P.Government Dental College, IGMC Shimla.Himachal Pradesh
  • Yue Qi Wang Master of Science - MS, Pharmacology, UCL

Want to know about tetrodotoxin poisoning? Are you finding it hard to differentiate between other toxins? Here are some easy-to-understand facts about tetrodotoxin poisoning.

By: Deepika Rana

Various kinds of puffer fish can cause tetrodotoxin (TTX) poisoning. TTX is a neurotoxin. It is notable for giving pufferfish eaters perioral numbness and is present in marine creatures.

Dive into a thorough investigation of TTX poisoning, including its fascinating history, the science underlying its effects and the critical actions to prevent and manage this toxin's consequences. Study all facets of TTX poisoning, including how it affects the environment and people's health.


Numerous marine animals contain the neurotoxin TTX. In Japan, the flesh of puffer fish, also known as fugu, is treasured and prepared only by chefs who have received special training and government certification. This is to ensure that the meat of the puffer fish is free of the deadly neurotoxin that is found in the liver, gonads, and skin. Regardless of these safety measures, fugu consumption is linked to numerous incidents of TTX poisoning each year.

Fish collected and prepared by unlicensed handlers generally result in poisonings. Cooking does not render the poison inactive because it is heat-stable. There are 26 recognised natural analogues of TTX. The toxin inhibits sodium channels, causing gastrointestinal, neurological and cardiac symptoms in poisoned people.

The antidote is presently unknown. Due to the variable TTX concentrations in puffer fish, the toxic dose is unknown. Purified toxins have a fatal dosage of 1-2 milligrams. The Centres for Disease Control and Prevention (CDC) has received reports of situations where eating as little as 1.4 ounces of puffer fish resulted in poisoning. Gastric lavage and mechanical ventilation are the only treatments for TTX poisoning that decrease fatalities until the toxin is removed from the body.

The Netherlands, the United Kingdom, France, Greece, and Italy have all reported finding TTX in bivalve shellfish, whereas amounts were small compared to the minimal lethal doses for humans. Thirty percent of the shellfish samples tested in New Zealand contained TTX. The concentrations were minimal, except for pipi (Paphies australis), a surf clam native to New Zealand, recording TTX at values of 0.044 mg/kg or higher. Bacterial or dinoflagellate species related to puffer fish synthesise TTX. The liver, gonads, and skin possess the majority of poison. Fugu is exclusively served in Japan from October to March because of its seasonal toxicity.

Only newts, toads, and frogs have TTX in terrestrial animals. Since TTX plays a defensive role in these species, its origin is endogenous. For instance, the epidermis of newts contains higher quantities of TTX than the liver, which supports the idea that TTX forms a defense against predators. TTX, a small, non-protein, heterocyclic organic molecule that is heat and water-stable.

TTX directly impacts the electrical activity of active sodium channels in neurons. It produces analgesia characteristics by blocking the start and conduction of electrical impulses in the peripheral nervous system, stimulating the chemoreceptor trigger zone in the medulla oblongata, and depressing the respiratory and vasomotor centres there.1,2


Ingesting seafood tainted with the TTX is the primary cause of poisoning. The toxin is naturally present in several distinct vertebrates and invertebrates of varying evolutionary distances. The toxin is present in the rough-skinned Western newts of the genus Taricha, the Eastern newt (Notophthalmus viridescens), and toads of the species Atelopus.

More than 20 different pufferfish species and certain angelfish are among the marine vertebrates that produces the toxin. Several species of the blue-ringed octopus, species of Niotha gastropods, and members of the group Naticidae (moon snails) are among the molluscs that carry TTX. Several species of starfish, various xanthid crabs, species of the phylum Chaetognatha (arrow worms), species of the phylum Nemertea (ribbon worms), some flatworms, and planarians of the genus Bipalium are among the other invertebrates that possess the toxin.

The fact that the animals themselves cannot generate the toxin explains why many distantly related taxa have evolved the capacity to produce TTX. The animals bioaccumulate the poison from their diets. The toxin is produced by bacteria, ingested by higher trophic level animals and gradually bioaccumulates.

Members of the genera Pseudoalteromonas, Pseudomonas, Vibrio, Aeromonas, Alteromonas, Shewanella, Roseobacter, Raoultella, Actinomycetes, Microbacterium, and Serratia are among the bacteria that are related to the creation of TTX. Those TTX-infected animals can withstand the toxin's neurological effects asthe sodium channel in these animals have a poor affinity for tetrodotoxin. As a result, the toxin does not prevent the opening of sodium channels in these species.

This toxin works by inhibiting voltage-gated sodium channels, which stops cell membranes from depolarising. This limits the movement of action potentials and prevents myocytes (muscle cells) and neurons from functioning.1 The table below displays the distribution of TTX in various animals and poisoning cases in different countries.

ChordataPufferfishJapan, Mexico, Bangladesh, Singapore, India, Hong Kong, China, Australia and the United StatesLiver, gonads and skin
PlatyhelminthesTurbellaria, FlatwormsWhole body
NemerteaRibbon wormsWhole body and digestive gland
MolluscaGastropodaJapan, Taiwan, China, New Zealand, Netherlands, United Kingdom, France, Greece, and ItalyWhole body, digestive gland, skin and salivary gland
AnnelidaPolychaetaWhole body
ArthropodaXanthidae crabsHorseshoe crabThailand, Japan, China, Hong Kong and TaiwanWhole body and eggs
EchinodermataStarfishWhole body
VertebrataPisces, Goby and AmphibiaSoutheast Asian countriesSkin, viscera, gonad, muscle, blood and eggs
Frogs and newtsSkin, egg, ovary, muscle, blood and liver3

Clinical presentation and symptoms

In 1941, Fukuda and Tani provided a clinical grading system for TTX poisoning. The quantity of TTX consumed, the interval between consumption and admission to the hospital, and any underlying illnesses are the three variables that affect the level of TTX intoxication.

The image below summarises the grading system of signs and symptoms.

Created by: Deepika Rana4,5

Paraesthesia, nausea, slurred speech, respiratory failure, aphonia, hypoxia, heart dysrhythmias, bradycardia, hypercapnia, and hypotension.

Diagnosis and medical assessment

Rapid and precise diagnosis is essential due to the symptoms' rapid progression and potential severity. The diagnostic procedure consists of:

Clinical evaluation

Healthcare providers examine the patient's symptoms, medical background, and exposure to tetrodotoxin sources, such as recent seafood eating.

Neurological assessment

Detailed neurological testing aims to assess muscle power, coordination, reflexes, and sensory abnormalities.

Laboratory tests

The diagnosis depends on food history since it lacks specific laboratory tests confirming TTX intake. The mouse bioassay is the gold standard technique accepted globally for assessing TTX toxicity in food matrices. The lack of specialist variations and limited sensitivity of biological tests prevent them from being entirely satisfactory.

Gas chromatography-mass spectrometry (GC-MS), immunoaffinity chromatography, high-performance liquid chromatography with post-column derivatization and fluorescence detection (HPLC-FLD), HPLC with ultraviolet (UV) detection, and liquid chromatography-mass spectrometry (LC-MS) are some of the analytical techniques for finding TTX in urine and blood samples of poisoned patients.

A particular enzyme-linked immunosorbent test (ELISA) assesses TTX in biological material in addition to approaches based on chromatography. Routine serum electrolyte, calcium, magnesium, and arterial blood gas (ABG) measurements are essential for excluding metabolic causes for diffuse sensory and motor neuron dysfunction.

Imaging studies

With the goal for doctors to rule out local lung pathology (such as aspiration pneumonia), patients with signs of cyanosis or respiratory insufficiency should get a chest x-ray. When a patient has severe abdominal discomfort or recurrent vomiting, get an upright x-ray of the abdomen to rule out blockage or hollow viscus perforation. 

Patients experiencing seizures or focal neurologic impairment need a brain computed tomography (CT) scan.2,4

Treatment and management

Due to the possible severity of symptoms, TTX poisoning requires immediate medical attention. Although there is no specific treatment, symptom management and supportive care are essential.

Supportive care

Give the ABC (airway, breathing, and circulation) thorough attention. Avoid making someone vomit. Muscle weakness and respiratory failure, which can happen shortly after ingesting TTX, may necessitate endotracheal intubation for delivering oxygen and airway protection. Fluids, pressors, and antiarrhythmics may need to be given intravenously (IV) in cases of cardiac dysfunction.

Monitoring and observation

Observe vital signs and oxygenation levels since patients can rapidly decompensate. Any changes in vital signs require immediate medical attention. Monitoring of heart function and evaluation of the patient for hypotension, dysrhythmias, and respiratory depression are imperative. It's crucial to check the patient for hypoxia, electrolyte imbalances, and hypoglycemia.


For all symptomatic individuals, the administration of activated charcoal is encouraged. Gastric lavage with a 2% sodium bicarbonate solution may help remove the unabsorbed toxin since TTX is less persistent in an alkaline environment. Gastric lavage happens when TTX ingestion introduces a life-threatening risk (often within an hour). Steroids, naloxone, cysteine, antihistamines, and cholinesterase inhibitors (neostigmine), among other recommended treatments, are not scientifically proven as beneficial.

Future treatment

Future successful treatment is possible. When oral TTX-poisoned mice were injected with a monoclonal neutralising antibody, 100% of the animals survived as opposed to 0% in the control group. There are currently no reports of its use in humans.2,8


Adopting safe eating habits when ingesting seafood and being aware of potential tetrodotoxin sources are two ways to prevent the poisoning. The following constitute crucial precautions.

Created by: Deepika Rana


How common is tetrodotoxin?

Although TTX poisoning is extremely rare, it is more common in Japan, Taiwan, and several Southeast Asian countries where puffer fish consumption is prevalent. Exact fatality rates are tough to obtain due to the disease's rarity.1

Can you survive tetrodotoxin poisoning?

The patient prognosis is favourable if they arrive at the emergency room conscious and survive the first 24 hours before experiencing respiratory arrest. Following that, symptoms often go away within 24 hours to 5 days.9

Is tetrodotoxin worse than cyanide?

One of the most potent neurotoxins, TTX is roughly 1200 times more lethal to humans than sodium cyanide (median lethal dose: 10 μg/kg versus 10 mg/kg).6,7


Due to its powerful effects on the neurological system, TTX poisoning, resulting from eating some marine animals like pufferfish, is a severe problem. Having a thorough understanding of TTX poisoning enables people to make better informed decisions. The adverse effects of the toxin can be reduced, making it safer to eat seafood by practising stringent culinary techniques and seeking prompt medical attention.


  1. Kotipoyina HR, Kong EL, Warrington SJ. Tetrodotoxin toxicity. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2023 [cited 2023 Aug 22]. Available from: http://www.ncbi.nlm.nih.gov/books/NBK507714/
  2. Tetrodotoxin toxicity: practice essentials, pathophysiology, etiology. 2021 Aug 9 [cited 2023 Aug 22]; Available from: https://emedicine.medscape.com/article/818763-overview
  3. Noguchi T, Onuki K, Arakawa O. Tetrodotoxin poisoning due to pufferfish and gastropods, and their intoxication mechanism. International Scholarly Research Notices [Internet]. 2011 Nov 30 [cited 2023 Aug 22];2011:e276939. Available from: https://www.hindawi.com/journals/isrn/2011/276939/
  4. Leung KSY, Fong BMW, Tsoi YK. Analytical challenges: determination of tetrodotoxin in human urine and plasma by lc-ms/ms. Mar Drugs [Internet]. 2011 Nov 8 [cited 2023 Aug 22];9(11):2291–303. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3229236/
  5. How CK, Chern CH, Huang YC, Wang LM, Lee CH. Tetrodotoxin poisoning. The American Journal of Emergency Medicine [Internet]. 2003 Jan 1 [cited 2023 Aug 22];21(1):51–4. Available from: https://www.sciencedirect.com/science/article/pii/S0735675702422097
  6. Lago J, Rodríguez LP, Blanco L, Vieites JM, Cabado AG. Tetrodotoxin, an extremely potent marine neurotoxin: distribution, toxicity, origin and therapeutical uses. Mar Drugs [Internet]. 2015 Oct 19 [cited 2023 Aug 23];13(10):6384–406. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4626696/
  7. Yang CC. Tetrodotoxin. In: Brent J, Burkhart K, Dargan P, Hatten B, Megarbane B, Palmer R, et al., editors. Critical Care Toxicology: Diagnosis and Management of the Critically Poisoned Patient [Internet]. Cham: Springer International Publishing; 2017 [cited 2023 Aug 23]. p. 2085–99. Available from: https://doi.org/10.1007/978-3-319-17900-1_39
  8. Haque MA, Islam QT, Ekram ARMS. Puffer Fish Poisoning. The Journal of Teachers Association RMC, Rajshahi [Internet]; 2008 Dec [cited 2023 Aug 23] TAJ 2008; 20(2): 199-202. Available from: https://citeseerx.ist.psu.edu/document?repid=rep1&type=pdf&doi=7918f861889677a817015b1b2d3f2e32e8ae6492
  9. Kheifets J, Rozhavsky B, Girsh Solomonovich Z, Marianna R, Soroksky A. Severe tetrodotoxin poisoning after consumption of lagocephalus sceleratus (Pufferfish, fugu) fished in Mediterranean Sea, treated with cholinesterase inhibitor. Case Reports in Critical Care [Internet]. 2012 Oct 9 [cited 2023 Aug 23];2012:e782507. Available from: https://www.hindawi.com/journals/cricc/2012/782507/
  10. Dhuhaibat ZKA, Zarzour T, Kasim Z, Zarzour T. Tetrodotoxin poisoning due to pufferfish ingestion in the united arab emirates. Cureus [Internet]. 2023 Jan 10 [cited 2023 Aug 24];15(1). Available from: https://www.cureus.com/articles/130552-tetrodotoxin-poisoning-due-to-pufferfish-ingestion-in-the-united-arab-emirate
This content is purely informational and isn’t medical guidance. It shouldn’t replace professional medical counsel. Always consult your physician regarding treatment risks and benefits. See our editorial standards for more details.

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Deepika Rana

Bachelor of Dental Surgery(BDS), Dentistry , H.P.Government Dental College, IGMC Shimla.Himachal Pradesh

Hi, I am Deepika Rana Dentist by profession finished my Clinical Research Certification Programme from Duke NUS Medical school, Singapore in 2022. I joined Klarity’s internship because of my ongoing desire to learn and educate others about medicine through Writing. I enjoy producing articles that give readers detailed information about a variety of ailments that can be accessed through the Health Library created by Klarity.

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