Bi Ma Zi

Ricin is the whole safety story of this drug and the reason the seed and the oil must never be discussed as one substance. It is a type 2 ribosome-inactivating protein: the B chain is a galactose-binding lectin that attaches to cell-surface glycoproteins and drives endocytosis, and the A chain is an RNA N-glycosidase that depurinates a single adenine in the sarcin-ricin loop of 28S rRNA, irreversibly halting protein synthesis. One molecule reaching the cytosol can inactivate ribosomes catalytically, and there is no antidote. Parenteral and inhalational lethal doses in the region of 5 to 10 micrograms per kilogram are cited; oral toxicity is far lower because absorption is poor and the seed coat is hard, but seeds must be chewed to release the toxin and deaths have followed ingestion. Reports put toxicity within reach of as few as two chewed seeds in a child, while survival after thirty seeds is also documented, so the dose-response is wide and unpredictable. Ingestion causes haemorrhagic gastroenteritis with vomiting and bloody diarrhoea, hypovolaemia, then hepatic, renal and cardiovascular failure over one to several days. Crucially, ricin does not partition into the oil and is denatured by the heat of processing, so pharmaceutical castor oil contains none of it. Purified ricin is a Schedule 1 chemical under the Chemical Weapons Convention and a controlled select agent in the United States and elsewhere; possessing or preparing it is a criminal matter quite apart from any clinical question.

A closely related lectin from the same seed. It is far less cytotoxic than ricin because its ribosome-inactivating activity is weaker and its cell entry less efficient, but it is a powerful haemagglutinin and is haemolytic if it reaches the bloodstream. It contributes to the toxicity of crude seed material and is one reason crude preparations behave less predictably than purified toxin.

A minor alkaloid of low toxicity in its own right, but of considerable practical importance as a forensic and clinical marker: ricinine is small, stable and renally excreted, so it can be measured in urine to confirm castor bean exposure when ricin itself cannot be detected. Hamelin and colleagues demonstrated this in a non-lethal ingestion. In suspected castor seed poisoning, urinary ricinine is the usable confirmatory test.

This is the active principle of castor oil, entirely separate from ricin. Intestinal lipases release free ricinoleic acid, which Tunaru and colleagues showed is a specific agonist at the EP3 prostanoid receptor. Acting on smooth muscle rather than on intestinal epithelium, it produces the laxative effect, and acting on uterine smooth muscle it produces the contractions behind castor oil's traditional use to induce labour: EP3-knockout mice show neither effect. This is a genuine, well-characterised pharmacology, and it is why castor oil is a stimulant laxative with real potency and real potassium and fluid consequences, not a bland emollient.

Potent respiratory and contact allergens responsible for the occupational asthma, rhinitis and dermatitis long documented in castor bean processing and in communities living near castor mills. They are a hazard of the dust and cake, not of the refined oil, and they act independently of ricin, so allergic reactions can occur at exposures far below any toxic dose.

The state materia medica of 659 CE contains the earliest Chinese entry for Bi Ma Zi, distinguishing locally grown from imported castor seed. Use is described in external and drawing applications rather than as a routine internal purgative.

Li Shizhen gathers the earlier accounts of Bi Ma Zi and records its principal traditional applications as topical: pounded seed applied as a paste to draw out toxin from sores and abscesses, and applied to points on the face or scalp in wind-stroke and facial deviation. He also records the pressed oil as a purgative. The seed is treated as a toxic (du) substance throughout.