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.
Puffer fish contain the potent neurotoxin tetrodotoxin.
Tetrodotoxin is probably synthesized by a bacterial or dinoflagellate species associated with the puffer fish. The toxin is concentrated in the liver, gonads, and skin. The level of toxicity is seasonal, and in Japan, fugu is only served from October through March. Tetrodotoxin acts to block diffusion of sodium through the sodium channel, preventing depolarization and propagation of action potentials in nerve cells. All of the observed toxicity is secondary to this blockade of the action potential.