Tetrodotoxin Toxicity

Updated: May 24, 2018
  • Author: Theodore I Benzer, MD, PhD; Chief Editor: Asim Tarabar, MD  more...
  • Print

Practice Essentials

Poisoning with the neurotoxin tetrodotoxin (TTX) occurs after ingestion of various species of puffer fish (see the image below).

Puffer fish. Puffer fish.

The flesh of the puffer fish (ie, fugu) is considered a delicacy in Japan. It is prepared by chefs specially trained and certified by the government to prepare the flesh free of the toxic liver, gonads, and skin. Despite these precautions, many cases of tetrodotoxin poisoning are reported each year in patients ingesting fugu.

Poisonings usually occur after eating fish caught and prepared by uncertified handlers.

The toxic dose is not clear because puffer fish have different concentrations of tetrodotoxin. A dose of 1-2 mg of purified toxin can be lethal. Reported cases from the Centers for Disease Control and Prevention (CDC) have documented toxicity with ingestion of as little as 1.4 ounces of puffer fish.

Tetrodotoxin also is found in the the following:

  • Gastropod mollusc

  • The eggs of horseshoe crabs

  • Newts of the genus Taricha

  • The skin of Atelopid frogs

  • The skin and viscera of porcupine fish, globefish, balloon fish, blowfish, sunfish, toadfish, blue-ringed octopus, and some species of salamanders [1]

Detection of tetrodotoxins in European bivalve shellfish in the United Kingdom along the English Channel has been reported, although concentrations were low in comparison to published minimum lethal doses for humans. [2]  



Puffer fish contain the potent neurotoxin tetrodotoxin. TTX is thought to be synthesized by a bacterial or dinoflagellate species associated with the puffer fish. [3, 4]

The toxin is concentrated in the liver, gonads, and skin. The level of toxicity is seasonal, and, in Japan, fugu is served only from October through March.

Tetrodotoxin is a heat-stable (except in alkaline environments) and water-soluble nonprotein.

It is a heterocyclic, small, organic molecule that acts directly on the electrically active sodium channel in nerve tissue (see the image below).

Chemical structure of tetrodotoxin. Chemical structure of tetrodotoxin.

Tetrodotoxin blocks diffusion of sodium through the sodium channel, thus preventing depolarization and propagation of action potentials in nerve cells.

All of the observed toxicity is secondary to blockade of the action potential. Tetrodotoxin acts on the central and the peripheral nervous systems (ie, autonomic, motor, sensory nerves).

Tetrodotoxin also stimulates the chemoreceptor trigger zone in the medulla oblongata and depresses the respiratory and vasomotor centers in that area.

Recent study using tetrodotoxin therapeutically shows that tetrodotoxin used in conjunction with bupivacaine prolonged the local anesthetic effect. [5] If tetrodotoxin begins to be used clinically, the incidence of toxicity may increase.




United States

Reports of tetrodotoxin poisoning are rare in the United States. A 1996 report documents three cases of tetrodotoxin toxicity from persons who ingested contaminated fugu imported by a coworker from Japan. [6] A 2014 report describes two patients in Minneapolis, Minnesota, who developed tetrodotoxin poisoning  after consuming dried puffer fish purchased during a recent visit to New York City; the patients noted that two friends who consumed the same fish had similar but milder symptoms and had not sought care. [7]


Despite the careful training and certification of fugu chefs in Japan, cases of mortality and morbidity from puffer fish ingestion continue to be reported. Estimates vary, but up to 50 deaths may occur each year from tetrodotoxin poisoning in Japan.


Mortality rates are difficult to calculate, but estimates of mortality approach 50%, even with modern supportive medical care. Patients who live through the acute intoxication (ie, first 24 h) usually recover without residual deficits. Recovery takes days to occur.


No known racial predilection exists. However, the poisoning is more common in Japanese people because of their dietary preferences for fugu.