Ricin

(BAN, USAN, rINN)

Chemical information

Ricino.
CAS — 9009-86-3.
NOTE. The title ricin is used for the castor seed in Chin. and Fr.

Profile

Ricin is a lectin present in castor seeds, the seeds of Ricinus communis (Euphorbiaceae). It is extremely toxic when given parenterally and the fatal dose by injection has been reported to be around 1 microgram/kg. The toxicity of orally ingested beans depends on how thoroughly they are chewed since the hard seed coat prevents absorption. Ingestion of as few as 3 castor seeds by a child and 4 by an adult may be fatal. Ricin may also be absorbed through abraded skin. It has potential use in aerosol form as an agent of chemical warfare. Toxic effects may be delayed for several days after exposure by any route. Early symptoms include severe gastrointestinal irritation, haemorrhage, vomiting, and diarrhoea, which may result in circulatory collapse. Abnormal liver function tests and pulmonary oedema have been reported. Ophthalmological disturbances ranging from irritation and conjunctivitis to optic nerve damage may occur; miosis and mydriasis have also been reported. Proteinuria, haematuria, and renal impairment may develop and serum creatinine levels may be raised. In severe cases haemolysis of the red blood cells with subsequent acute renal failure may occur. Fatalities due to multiorgan failure have occurred. If the patient presents within 1 hour of ingestion any seeds may be removed by gastric lavage and activated charcoal given. Treatment thereafter is symptomatic. After expression of the oil from castor seeds, the ricin remaining in the seed cake or ‘pomace’ is destroyed by steam treatment. The detoxified pomace is used as a fertiliser. Ricin conjugated with monoclonal or polyclonal antibodies is being studied in the treatment of cancers; zolimomab aritox is an example of such a conjugate. Some of these conjugates have been investigated for various malignancies, particularly leukaemias and lymphomas. To x i c i t y . A report of ricin toxicity after partial chewing and ingestion of 10 to 15 castor oil seeds,1 and reviews2-4 of ricin toxicity, including its potential as an agent of chemical warfare.
1. Aplin PJ, Eliseo T. Ingestion of castor oil plant seeds. Med J Aust 1997; 167: 260–1
2. Bradberry SM, et al. Ricin poisoning. Toxicol Rev 2003; 22: 65–70
3. Lord MJ, et al. Ricin: mechanisms of cytotoxicity. Toxicol Rev 2003; 22: 53–64
4. Audi J, et al. Ricin poisoning: a comprehensive review. JAMA 2005; 294: 2342–51.

Uses.

References to the use of ricin conjugates with monoclonal antibodies in the treatment of cancer.
1. Byers VS, et al. Phase I study of monoclonal antibody-ricin A chain immunotoxin XomaZyme-791 in patients with metastatic colon cancer. Cancer Res 1989; 49: 6153–60
2. Oratz R, et al. Antimelanoma monoclonal antibody-ricin A chain immunoconjugate (XMMME-001-RTA) plus cyclophosphamide in the treatment of metastatic malignant melanoma: results of a phase II trial. J Biol Response Mod 1990; 9: 345–54
3. Anonymous. Application considered for immunotoxin in treatment of graft-vs-host disease. JAMA 1991; 265: 2041–2
4. Amlot PL, et al. A phase I study of an anti-CD22-deglycosylated ricin A chain immunotoxin in the treatment of B-cell lymphomas resistant to conventional therapy. Blood 1993; 82: 2624–33
5. Senderowicz AM, et al. Complete sustained response of a refractory, post-transplantation, large B-cell lymphoma to an antiCD22 immunotoxin. Ann Intern Med 1997; 126: 882–5
6. Multani PS, et al. Phase II clinical trial of bolus infusion anti-B4 blocked ricin immunoconjugate in patients with relapsed B-cell non-Hodgkin’s lymphoma. Clin Cancer Res 1998; 4: 2599–2604
7. Dinndorf P, et al. Phase I trial of anti-B4-blocked ricin in pediatric patients with leukemia and lymphoma. J Immunother 2001; 24: 511–16
8. Schnell R, et al. Clinical evaluation of ricin A-chain immunotoxins in patients with Hodgkin’s lymphoma. Ann Oncol 2003; 14: 729–36
9. Tsimberidou AM, et al. Anti-B4 blocked ricin post chemotherapy in patients with chronic lymphocytic leukemia—long-term follow-up of a monoclonal antibody-based approach to residual disease. Leuk Lymphoma 2003; 44: 1719–25.
Published May 08, 2019.