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In addition to disease caused by direct infection, some foodborne diseases are caused by the presence of a toxin in the food that was produced by a microbe in the food. For example, the bacterium Staphylococcus aureus can grow in some foods and produce a toxin that causes intense vomiting. The rare but deadly disease botulism occurs when the bacterium Clostridium botulinum grows and produces a powerful paralytic toxin in foods. These toxins can produce illness even if the microbes that produced them are no longer there.

Other toxins and poisonous chemicals can cause foodborne illness. People can become ill if a pesticide is inadvertently added to a food, or if naturally poisonous substances are used to prepare a meal. Every year, people become ill after mistaking poisonous mushrooms for safe species, or after eating poisonous reef fishes.