The skin of these newts contains tetrodotoxin, which is about 100 times as toxic as potassium cyanide. 25 milligrams of this toxin would be sufficient to kill an adult human. One website (http://www.env.gov.bc.ca/wld/frogwatch/whoswho/factshts/rsnewt.htm) claims that one newt contains enough toxin to kill 25,000 mice; this implies that a single newt contains enough toxin to kill several humans of average body weight. However, the toxicity of rough-skinned newts varies across their range and probably between individuals.

Newts are not a food item for humans, but the tropical pufferfish -- which also contains tetrodotoxin -- is sometimes eaten. The Japanese serve them as "fugu" and, despite the safety of properly-prepared fugu, inexpert cooking results in a few dozen cases of tetrodotoxin poisoning each year. The effects of fugu poisoning are probably similar to what one would see in poisoning from eating a rough-skinned newt.

Tetrodotoxin blocks nerve channels. Early symptoms of poisoning are numbness of the tongue, lips, and face. If a substantial amount of the poison has been eaten then general paralysis follows. Death occurs due to paralysis of the diaphragm and interruption of the heartbeat.