Ricin is a plant poison. The seeds of Ricinus communis (also known as the castor bean plant, see Fig. 1+2) from the Euphorbiaceae family contain about 1-2% ricin. The poison provides the plant with natural protection from insect pests. This subtropical to tropical plant is predominantly cultivated on a large scale in India, Brazil and China for the production of castor oil. It is frequently found as a magnificent ornamental plant in the garden.
  • Fig. 1: Blossoming castor bean bush
  • Fig. 2: Seed kernels of Ricinus communis

Ricin, a Dual-Use Substance

The ricin-producing plant is of economic interest for the production of castor oil and the numerous industrial, medical and cosmetic products derived thereof (Worbs et al., 2011). The oil contains high levels of the unusual fatty acid ricinoleic acid that is valued for its unique chemical properties. Furthermore, with respect to medical applications, the ability of the A-subunit to induce cell death has been exploited for the development of immunotoxins. Immunotoxins combine the toxic principle of a toxin with the exquisite binding specificity of antibodies in one chimeric molecule (Strebhardt et al., 2008). Ricin A-chain was one of the first examples of a toxin coupled to monoclonal antibodies against cell surface proteins and was used experimentally for the treatment of various cancers (Zhou et al., 2010; Spitler et al., 1987; Frankel et al., 2009; Schindler et al., 2011). However, unexpected side effects like the so-called vascular leak syndrome hampered the efforts (Wu et al., 2005; Vitetta et al., 1993; Baluna et al., 1997), but progress has been made recently including phase I or III clinical trials, respectively (Schindler et al., 2011; Furman et al. 2011).

On the other hand, ricin has attracted dangerous interest as it has a history of military, criminal and terroristic use. The toxin has been explored for potential military use by different nations. It was included in different weapons programs during World War II (codename: compound W), and weaponised material was later produced until the 1980s (Audi et al., 2005; Franz et al., 1997; Zilinska et al., 1997; Kirby et al., 2004). Based on its history, ricin is a prohibited substance both under the Chemical Weapons Convention (CWC, schedule 1 compound) and the Biological Weapons Convention (BWC) and its possession or purification is strictly regulated and controlled by the Organization for the Prohibition of Chemical Weapons (OPCW). The world-wide availability of the plant has also made ricin a potential agent of bioterrorism. It is therefore listed as category B agent of potential bioterrorism risk by the Centers for Disease Control and Prevention (Schieltz et al., 2011; Moran et al., 2002). Ricin has gained notoriety as the most likely agent used in the assassination of the Bulgarian dissident Georgi Markov in London in 1978 and the attempted murder of Vladimir Kostov in Paris (Crompton et al., 1980). In the past, the focus fell on the toxin for criminal use and various attempted acts of bioterrorism. To provide a few examples, ricin was found in threat letters to members of the US Senate and the White House (in 2003/2004); Ricinus communis seeds and means for the preparation of ricin have been discovered during a raid against terrorists in London in 2002. In a number of cases worldwide, the production and possession of ricin has been well documented. These aspects of ricin are reviewed by Griffiths, 2011.

Chemical structure and properties

Fig. 3: A-B protein toxin ricin (2AAI.pdb). B-chain blue ribbon with bound carbohydrates, A-chain red ribbon. Fig. 3: A-B protein toxin ricin (2AAI.pdb). B-chain blue ribbon with bound carbohydrates, A-chain red ribbon.
Ricin is a glycoprotein which inhibits intracellular protein synthesis through ribosomal inactivation. It is thought that because of its enzymatic property a single ricin molecule can translocate to the cytosol and thus kill the cell.

It has a molecular weight of around 64 kDa (approx. 570 amino acids) and is composed of two structural sub-units, the A and B chains, which are connected by an intermolecular disulphide bond (see Fig. 3). The B chain has two binding sites where specific glycans latch on to the cell surface (lectin) and stimulate endocytosis in the cytosol of the target cells. The A chain is an enzyme (RNA-N-glycosidase) that inactivates the ribosomes of the endoplasmic reticulum by removing a specific adenine.


The toxicity of ricin greatly depends on the route of exposure. For example, oral exposure is much less toxic than inhalation or injection exposure (for a review see Worbs et al., 2011).

LD50 in mice:
Oral 20 mg/kg
Injection intravenously 0.002–0.008 mg/kg
Inhalation 0.003–0.01 mg/kg

However, there are several reasons why data extrapolated from animal tests to humans should be interpreted with great caution. According to the literature, the oral toxicity of ricin in humans varies from 0.003 to 20 mg/kg.

Analytical methods

  • Immunoassays: screening for ricin in complex matrices, also in multiplex formats (Pauly et al., 2009; Poli et al.,1994; He et al.,2010)
  • Mass spectrometry: detection of peptide fingerprint, differentiation of cultivars (Kull et al., 2012; Östin et al.,2007; Brinkworth et al.,2010)
  • Functional methods: e.g. measurement of cytotoxicity on cells (Pauly et al., 2012); activity-based MS-assays to detect the release of adenine (Becher et al., 2007; Kalb and Barr, 2009)


Audi, J.; Belson, M.; Patel, M.; Schier, J.; Osterloh, J. (2005). Ricin poisoning: A comprehensive review. J. Am. Med. Assoc. 294, 2342–2351.

Baluna, R.; Vitetta, E.S. (1997). Vascular leak syndrome: A side effect of immunotherapy. Immunopharmacology 37, 117–132.

Becher, F.; Duriez, E.; Volland, H.; Tabet, J.C.; Ezan, E. (2007). Detection of functional ricin by immunoaffinity and liquid chromatography-tandem mass spectrometry. Anal. Chem. 79, 659–665.

Brinkworth, C.S. (2010). Identification of ricin in crude and purified extracts from castor beans using on-target tryptic digestion and MALDI mass spectrometry. Anal. Chem. 82, 5246–5252.

Crompton, R.; Gall, D. (1980). Georgi Markov-death in a pellet. Med. Leg. J. 48, 51–62.

Frankel, A.E.; Woo, J.-H.; Neville, D.M. (2009). Principles of Cancer Biotherapy, 5th ed.; Springer Netherlands: Dodrecht, The Netherlands

Franz, D.R.; Jaax, N.K. (1997). Ricin Toxin. In Medical Aspects of Chemical and Biological Warfare; Sidell, F.R., Takafuji, E.T., Franz, D.R., Eds.; TMM Publications: Washington, DC, USA, 631–642.

Furman, R.R.; Grossbard, M.L.; Johnson, J.L.; Pecora, A.L.; Cassileth, P.A.; Jung, S.-H.; Peterson, B.A.; Nadler, L.M.; Freedman, A.; Bayer, R.-L.; et al. (2011). A phase III study of anti-B4-blocked ricin as adjuvant therapy post-autologous bone marrow transplant: CALGB 9254. Leuk. Lymphoma 52, 587–596.

Griffiths, G.D. (2011). Understanding ricin from a defensive viewpoint. Toxins (Basel) 3, 1373-92.

He, X.; McMahon, S.; Henderson, T.D., II; Griffey, S.M.; Cheng, L.W. (2010). Ricin toxicokinetics and its sensitive detection in mouse sera or feces using immuno-PCR. PLoS One 5, 0012858.

Kalb, S.R.; Barr, J.B. (2009) Mass spectrometric detection of ricin and its activity in food and clinical samples. Anal. Chem. 81, 2037–2042.

Kirby, R. (2004) Ricin toxin: A military history. CML Army Chem. Rev. PB 3–04, 38–40.

Kull, S., Kirchner, S., Pauly, D., Stoermann, B., Dorner, M.B., Lasch, P., Naumann, D., Dorner, B.G. (2010). Multiplex detection of microbial and plant toxins by immunoaffinity enrichment and matrix-assisted laser desorption/ionization mass spectrometry. Anal. Chem. 82, 2916-24.

Moran, G.J. (2002). Threats in bioterrorism. II: CDC category B and C agents. Emerg. Med. Clin. North Am. 20, 311–330. Östin, A.; Bergström, T.; Fredriksson, S.A.; Nilsson, C. (2007). Solvent-assisted trypsin digestion of ricin for forensic identification by LC-ESI MS/MS. Anal. Chem. 79, 6271–6278.

Pauly, D., Kirchner, S., Stoermann, B., Schreiber, T., Kaulfuss, S., Schade, R., Zbinden, R., Avondet, M.A., Dorner, M.B., Dorner, B.G. (2009). Simultaneous quantification of five bacterial and plant toxins from complex matrices using a multiplexed fluorescent magnetic suspension assay. Analyst 134, 2028 – 2039.

Pauly, D., Worbs, S., Kirchner, S., Shatohina, O., Dorner, M.B., Dorner, B.G. (2012). Real-Time Cytotoxicity Assay for Rapid and Sensitive Detection of Ricin from Complex Matrices. PLoS ONE 7 (4): e35360

Poli, M.A.; Rivera, V.R.; Hewetson, J.F.; Merrill, G.A. (1994). Detection of ricin by colorimetric and chemiluminescence ELISA. Toxicon 32, 1371–1377.

Schieltz, D.M.; McGrath, S.C.; McWilliams, L.G.; Rees, J.; Bowen, M.D.; Kools, J.J.; Dauphin, L.A.; Gomez-Saladin, E.; Newton, B.N.; Stang, H.L.; et al. (2011). Analysis of active ricin and castor bean proteins in a ricin preparation, castor bean extract, and surface swabs from a public health investigation. Forensic. Sci. Int. 209, 70–79.

Schindler, J.; Gajavelli, S.; Ravandi, F.; Shen, Y.; Parekh, S.; Braunchweig, I.; Barta, S.; Ghetie, V.; Vitetta, E.; Verma, A. (2011). A phase I study of a combination of anti-CD19 and anti-CD22 immunotoxins (combotox) in adult patients with refractory B-lineage acute lymphoblastic leukaemia. Br. J. Haematol., 1–6.

Spitler, L.E.; del Rio, M.; Khentigan, A.; Wedel, N.I.; Brophy, N.A.; Miller, L.L.; Harkonen, W.S.; Rosendorf, L.L.; Lee, H.M.; Mischak, R.P.; et al. (1987). Therapy of patients with malignant melanoma using a monoclonal antimelanoma antibody-ricin A chain immunotoxin. Cancer Res. 47, 1717–1723. Strebhardt, K.; Ullrich, A. (2008). Paul Ehrlich’s magic bullet concept: 100 years of progress. Nat. Rev. Cancer 8, 473–480.

Vitetta, E.S.; Thorpe, P.E.; Uhr, J.W. (1993). Immunotoxins: Magic bullets or misguided missiles? Trends Pharmacol. Sci. 14, 148–154.

Worbs, S., Köhler, K., Pauly, D., Avondet, M.A., Schaer, M., Dorner, M.B., Dorner, B.G. (2011). Ricinus communis intoxications in human and veterinary medicine - a summary of real cases. Toxins 3(10):1332-72.

Wu, A.M.; Senter, P.D. (2005). Arming antibodies: Prospects and challenges for immunoconjugates. Nat. Biotechnol. 23, 1137–1146.

Zhou, X.-X.; Ji, F.; Zhao, J.-L.; Cheng, L.-F.; Xu, C.-F. (2010). Anti-cancer activity of anti-p185Her-2 ricin A chain immunotoxin on gastric cancer cells. J. Gastroenterol. Hepatol. 25, 1266–1275.

Zilinskas, R.A. (1997). Iraq’s biological weapons. J. Am. Med. Assoc. 278, 418–424.