"All parts of the tree contain strong toxins.[10] Its milky white sap contains phorbol and other skin irritants, producing strong allergic contact dermatitis.[11]

Standing beneath the tree during rain will cause blistering of the skin from mere contact with this liquid: even a small drop of rain with the sap in it will cause the skin to blister. Burning the tree may cause ocular injuries if the smoke reaches the eyes.[12] Contact with its milky sap (latex) produces bullous dermatitis, acute keratoconjunctivitis and possibly large corneal epithelial defects.[13]

Although the fruit is potentially fatal if eaten, no such occurrences have been reported in the modern literature.[14] Ingestion can produce severe gastroenteritis with bleeding, shock, and bacterial superinfection, as well as the potential for airway compromise due to edema.[15]

When ingested, the fruit is reportedly "pleasantly sweet" at first, with a subsequent "strange peppery feeling ... gradually progress[ing] to a burning, tearing sensation and tightness of the throat." Symptoms continue to worsen until the patient can "barely swallow solid food because of the excruciating pain and the feeling of a huge obstructing pharyngeal lump."[5]

In some parts of its range, many trees carry a warning sign – for example on Curaçao – while others are marked with a red "X" on the trunk to indicate danger. In the French Antilles the trees are often marked with a painted red band roughly 1 metre (3 ft) above the ground.[16]

Although the plant is toxic to many birds and other animals, the black-spined iguana (Ctenosaura similis) is known to eat the fruit and even live among the limbs of the tree.[10]

The tree contains 12-deoxy-5-hydroxyphorbol-6-gamma-7-alpha-oxide, hippomanins, mancinellin, and sapogenin. Phloracetophenone-2,4-dimethylether is present in the leaves, while the fruits possess physostigmine.[17]

A poultice of arrowroot (Maranta arundinacea) was used by the Arawak and Taíno as an antidote against such poisons.[18] The Caribs were known to poison the water supply of their enemies with the leaves.[12] Spanish explorer Juan Ponce de León died shortly after an injury incurred in battle with the Calusa in Florida—being struck by an arrow that had been poisoned with manchineel sap.[19]"