Ricin and Ricinus communis in pharmacology and toxicology-from ancient use and “Papyrus Ebers” to modern perspectives and “poisonous plant of the year 2018”

  • Heike FrankeEmail author
  • Reinhold Scholl
  • Achim Aigner


While probably originating from Africa, the plant Ricinus communis is found nowadays around the world, grown for industrial use as a source of castor oil production, wildly sprouting in many regions, or used as ornamental plant. As regards its pharmacological utility, a variety of medical purposes of selected parts of the plant, e.g., as a laxative, an anti-infective, or an anti-inflammatory drug, have been described already in the sixteenth century bc in the famous Papyrus Ebers (treasured in the Library of the University of Leipzig). Quite in contrast, on the toxicological side, the native plant has become the “poisonous plant 2018” in Germany. As of today, a number of isolated components of the plant/seeds have been characterized, including, e.g., castor oil, ricin, Ricinus communis agglutinin, ricinin, nudiflorin, and several allergenic compounds. This review mainly focuses on the most toxic protein, ricin D, classified as a type 2 ribosome-inactivating protein (RIP2). Ricin is one of the most potent and lethal substances known. It has been considered as an important bioweapon (categorized as a Category B agent (second-highest priority)) and an attractive agent for bioterroristic activities. On the other hand, ricin presents great potential, e.g., as an anti-cancer agent or in cell-based research, and is even explored in the context of nanoparticle formulations in tumor therapy. This review provides a comprehensive overview of the pharmacology and toxicology-related body of knowledge on ricin. Toxicokinetic/toxicodynamic aspects of ricin poisoning and possibilities for analytical detection and therapeutic use are summarized as well.


Ricinus communis Papyrus Ebers Ricin Castor oil Intoxication Nanoparticles Immunotoxins Tumor therapy 



Before Christ


Biological and Toxin Weapons Convention


Castor bean allergenic fraction


Centers for Disease Control and Prevention


Carcinoembryonic antigen


Central nervous system


Chemical Weapons Convention


Enzyme-linked immunosorbent assay


European Medicines Agency


Enhanced permeability and retention


Endoplasmic reticulum


Energy return-on-energy investment


Establishment of Quality Assurance for the Detection of Biological Toxins of Potential Bioterrorism Risk


Joint Food and Agriculture Organization


Food and Drug Administration


Histidine-rich fusogenic peptide


Hepatitis B virus


Human epidermal growth factor receptor 2


Immunoglobulin G






International Union of Pure and Applied Chemistry


Lethal dose 50%


Lateral flow assay


Liquid chromatography/mass spectrometry


Matrix-assisted laser desorption/ionization time-of-flight


Mannose receptor


Multiwalled carbon nanotubes


Organization for the Prohibition of Chemical Weapons


Pokeweed anti-viral proteins


Polymerase chain reaction


Polyethylene glycol


Reactive oxygen species


Ricinus communis agglutinin


Ribosome-inactivating protein type 2


Ricin A chain


Ricin B chain


RNA interference


Virus-like particles


Vascular lead syndrome


World Health Organization



Parts of this article on the history of the plant Ricinus communis in the Papyrus Ebers were presented at the Symposium on the Occasion of the 30. Anniversary of the Postgraduate Study Program (PGS) “Toxicology and Environmental Protection” at the University of Leipzig (March 23, 2018). PGS graduation theses by Jörg Pietsch (2004), Gabriele Baranius (2009), and Thorsten Meißner (2017) as well as a study work prepared by Avina Graefe (2012) contributed to this review article and are greatly acknowledged. The authors are grateful to Dr. Jens Grosche (Effigos AG) for providing Fig. 4. The authors also wish to thank Adelgunde Graefe (PGS “Toxicology and Environmental Protection,” University of Leipzig) and Thomas Gruner (Library of the Medical Faculty, University of Leipzig) for their support.

Author contribution statement

HF, RS, and AA wrote the manuscript. HF took the photos, HF and AA created figures and tables. All authors read and approved the manuscript.

Compliance with ethical standards

Not applicable.

Conflict of interest

The authors declare that they have no conflicts of interest.

Supplementary material

210_2019_1691_Fig5_ESM.png (7.7 mb)
Suppl. Figure 1

Examples of the world wide distribution of the plant Ricinus communis: (A) La Reunion (on a roadside, up to 10 m high); (B) La Reunion (forest landscape, accompanied by palms); (C) Namibia (Chobe National Park); (D) Madagaskar (Tulear); (E) Vietnam (Hanoi); (F) Ecuador; (G) Costa Rica (Rio Tarcoles); (H) Germany (Botanical Garden, Leipzig). (PNG 7863 kb)

210_2019_1691_MOESM1_ESM.tif (15.4 mb)
High Resolution Image (TIF 15726 kb)
210_2019_1691_MOESM2_ESM.pptx (459 kb)
Suppl. Figure 2 Amino acid sequence alignment of ricin in comparison with the type 1 RIPs Gelonin, Trichosanthin, Momordin, Bouganin, Pokeweed anti-viral protein (PAP), Saponin, and Dianthin. Alignment was performed using Clutal Omega ( (PPTX 458 kb) (PPTX 458 kb)
210_2019_1691_MOESM3_ESM.pptx (235 kb)
Suppl. Figure 3 Amino acid sequence alignment of ricin and mistletoe lectin-1 from Viscum album. Colors indicate sequence domains encoding for the signal peptide, A-chain, linker, and B-chain. Alignment was performed using Clutal Omega ( Asterisks indicate sequence identities. (PPTX 234 kb)
210_2019_1691_MOESM4_ESM.pptx (69 kb)
Suppl. Figure 4 Toxic effects of ricin (PPTX 69 kb)
210_2019_1691_MOESM5_ESM.pptx (69 kb)
Suppl. Figure 5 Examples of the different applications of castor oil and its derivatives today (PPTX 69 kb)
210_2019_1691_MOESM6_ESM.docx (27 kb)
Suppl. Table 1 Examples of representative LD50 values of different kinds of toxins (DOCX 26.8 kb)


  1. Abal P, Louzao MC, Antelo A, Alvarez M, Cagide E, Vilariño N, Vieytes MR, Botana LM (2017) Acute oral toxicity of tetrodotoxin in mice: determination of lethal dose 50 (LD50) and no observed adverse effect level (NOAEL). Toxins (Basel) 9(3):pii: E75. Google Scholar
  2. Abbas M, Ali A, Arshad M, Atta A, Mehmood Z, Tahir IM, Iqbal M (2018) Mutagenicity, cytotoxic and antioxidant activities of Ricinus communis different parts. Chem Cent J 12(1):3. Google Scholar
  3. Abdul WM, Hajrah NH, Sabir JSM, Al-Garni SM, Sabir MJ, Kabli SA, Saini KS, Bora RS (2018) Therapeutic role of Ricinus communis L. and its bioactive compounds in disease prevention and treatment. Asian Pac J Trop Med 11(3):177–185Google Scholar
  4. Amlot PL, Stone MJ, Cunningham D, Fay J, Newman J, Collins R, May R, McCarthy M, Richardson J, Ghetie V et al (1993) 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 82:2624–2633Google Scholar
  5. Amouri M, Mohellebi F, Zaid TA, Aziza M (2017) Sustainability assessment of Ricinus communis biodiesel using LCA approach. Clean Techn Environ Policy 19:749–760. Google Scholar
  6. Araki T, Funatsu G (1987) The complete amino acid sequence of the B-chain of ricin E isolated from small-grain castor bean seeds. Ricin E is a gene recombination product of ricin D and Ricinus communis agglutinin. Biochim Biophys Acta 911:191–200Google Scholar
  7. Arnold W (2017) Rizinus, Wunderbaum - Ricinus communis: Accessed 18 March 2019
  8. Ashley CE, Carnes EC, Phillips GK, Durfee PN, Buley MD, Lino CA, Padilla DP, Phillips B, Carter MB, Willman CL, Brinker CJ, Caldeira Jdo C, Chackerian B, Wharton W, Peabody DS (2011) Cell-specific delivery of diverse cargos by bacteriophage MS2 virus-like particles. ACS Nano 5:5729–5745Google Scholar
  9. Audi J, Belson M, Patel M, Schier J, Osterloh J (2005) Ricin poisoning: a comprehensive review. JAMA 294:2342–2351. PMID 16278363 Google Scholar
  10. Balint GA (1974) Ricin: the toxic protein of castor oil seeds. Toxicology 2:77–102Google Scholar
  11. Baluna R, Vitetta ES (1997) Vascular leak syndrome: a side effect of immunotherapy. Immunopharmacology 37:117–132Google Scholar
  12. Baluna R, Rizo J, Gordon BE, Ghetie V, Vitetta ES (1999) Evidence for a structural motif in toxins and interleukin-2 that may be responsible for binding to endothelial cells and initiating vascular leak syndrome. Proc Natl Acad Sci U S A 96:3957–3962Google Scholar
  13. Bharadwaj S, Rathore SS, Ghosh PC (2006) Enhancement of the cytotoxicity of liposomal ricin by the carboxylic ionophore monensin and the lysosomotropic amine NH4Cl in Chinese hamster ovary cells. Int J Toxicol 25:349–359Google Scholar
  14. Bigi MFMA, Torkomian VLV, de Groote STCS, Hebling MJB, Bueno OC, Pagnocca FC, Fernandes JB, Vieira PC, da Silva MFGF (2004) Activity of Ricinus communis (Euphorbiaceae) and ricinine against the leaf-cutting ant Atta sexdens rubropilosa (hymenoptera: Formicidae) and the symbiotic fungus Leucoagaricus gongylophorus. Pest Manag Sci 60:933–938Google Scholar
  15. Bilge A, Howell-Clark J, Ramakrishnan S, Press OW (1994) Degradation of ricin A chain by endosomal and lysosomal enzymes-the protective role of ricin B chain. Ther Immunol 1:197–204Google Scholar
  16. Blakey DC, Watson GJ, Knowles PP, Thorpe PE (1987) Effect of chemical deglycosylation of ricin A chain on the in vivo fate and cytotoxic activity of an immunotoxin composed of ricin A chain and anti-Thy 1.1 antibody. Cancer Res 47:947–952Google Scholar
  17. Bourrie BJ, Casellas P, Blythman HE, Jansen FK (1986) Study of the plasma clearance of antibody--ricin-A-chain immunotoxins. Evidence for specific recognition sites on the A chain that mediate rapid clearance of the immunotoxin. Eur J Biochem 155:1–10Google Scholar
  18. Bradberry SM, Dickers KJ, Rice P, Griffiths GD, Vale JA (2003) Ricin poisoning. Toxicol Rev 22(1):65–70Google Scholar
  19. Brey RN III, Mantis NJ, Pincus SH, Vitetta ES, Smith LA, Roy CJ (2016) Recent advances in the development of vaccines against ricin. Hum Vaccin Immunother 5:1196–1201. Google Scholar
  20. Buch C (2018) Pflanzenporträts 2018; Ricinus communis - Rizinus, Wunderbaum (Euphorbiaceae), p 1–7, Bochumer Botanischer Verein, wwwbotanik-bochumde. Accessed 18 March 2019
  21. Buonocore C, Alipour M, Omri A, Pucaj K, Smith MG, Suntres ZE (2011) Treatment of ricin A-chain-induced hepatotoxicity with liposome-encapsulated N-acetylcysteine. J Drug Target 1:1–9. ISSN 1061-186X print/ISSN 1029-2330 online. Google Scholar
  22. Burrows WD, Renner SE (1999) Biological warfare agents as threats to potable water. Environ Helth Perspekt 107:975–984Google Scholar
  23. Butterworth AG, Lord JM (1983) Ricin and Ricinus communis agglutinin subunits are all derived from a single-size polypeptide precursor. Eur J Biochem 137:57–65. Google Scholar
  24. Byers VS, Rodvien R, Grant K, Durrant LG, Hudson KH, Baldwin RW, Scannon PJ (1989) Phase I study of monoclonal antibody-ricin A chain immunotoxin XomaZyme-791 in patients with metastatic colon cancer. Cancer Res 49:6153–6160Google Scholar
  25. Cazal C d M, Batalhão JR, Domingues Vde C, Bueno OC, Filho ER, Forim MR, da Silva MF, Vieira PC, Fernandes JB (2009) High-speed counter-current chromatographic isolation of ricinine, an insecticide from Ricinus communis. J Chromatogr A 1216(19):4290–4294. Google Scholar
  26. Challoner KR, McCarron MM (1990) Castor bean intoxication: review of reported cases. Ann Emerg Med 19:1177–1183Google Scholar
  27. Chen Z, Zhang J, Chen G (2008) Simultaneous determination of flavones and phenolic acids in the leaves of Ricinus communis Linn. By capillary electrophoresis with amperometric detection. J Chromatogr B Analyt Technol Biomed Life Sci 863(1):101–106. Google Scholar
  28. Cook DL, David J, Griffiths GD (2006) Retrospective identification of ricin in animal tissues following administration by pulmonary and oral routes. Toxicology 223:61–70Google Scholar
  29. Crompton R, Gall D (1980) Georgi Markov - death in a pellet. Medico-Legal J 48:51–62Google Scholar
  30. Dai J, Zhao L, Yang H, Guo H, Fan K, Wang H, Qian W, Zhang D, Li B, Wang H et al (2011) Identification of a novel functional domain of ricin responsible for its potent toxicity. J Biol Chem 286:12166–12171Google Scholar
  31. Darby SM, Miller ML, Allen RO (2001) Forensic determination of ricin and the alkaloid marker ricinine from castor bean extracts. J Forensic Sci 46(5):1033–1042 PMID: 11569541Google Scholar
  32. de la Cruz R, Pastor AM, Delgado-García JM (1994) The neurotoxic effects of Ricinus communis agglutinin-II. J Toxicol Toxin Rev 14(1):1–46. Google Scholar
  33. Despeyroux D, Walker N, Pearce M, Fisher M, McDonnell M, Bailey SC, Griffiths GD, Watts P (2000) Characterization of ricin heterogeneity by electrospray mass spectrometry, capillary electrophoresis, and resonant mirror. Anal Biochem 279:23–36Google Scholar
  34. Deus-de-Oliveira N, Felix SP, Carrielo-Gama C, Fernandes KV, Damatta RA, Machado OL (2011) Identification of critical amino acids in the IgE epitopes of Ric c 1 and Ric c 3 and the application of glutamic acid as an IgE blocker. PLoS One 6(6):e21455. Google Scholar
  35. Diac M, Matei MC, Manea C, Schiopu C, Iliescu DB, Furnica C, Chistol RO, Knieling A (2017) Intoxication with ricin-biochemical weapon. Rev Chim 68(6):1329–1332Google Scholar
  36. Diaz R, Pallares V, Cano-Garrido O, Serna N, Sanchez-Garcia L, Falgas A, Pesarrodona M, Unzueta U, Sanchez-Chardi A, Sanchez JM, Casanova I, Vazquez E, Mangues R, Villaverde A (2018) Selective CXCR4(+) cancer cell targeting and potent antineoplastic effect by a nanostructured version of recombinant ricin. Small 14:e1800665Google Scholar
  37. Dimitriadis GJ, Butters TD (1979) Liposome-mediated ricin toxicity in ricin-resistant cells. FEBS Lett 98:33–36Google Scholar
  38. Duracova M, Klimentova J, Fucikova A, Dresler J (2018) Proteomic methods of detection and quantification of protein toxins. Toxins 10:99. doi:
  39. Eastmond PJ (2004) Cloning and characterization of the acid lipase from castor beans. J Biol Chem 279(44):45540–45545Google Scholar
  40. Elimam AM, Elmalik KH, Ali FS (2009) Larvicidal, adult emergence inhibition and oviposition deterrent effects of foliage extract from Ricinus communis L against Anopheles arabiensis and Culex quinquefasciatus in Sudan. Trop Biomed 26(2):130–139Google Scholar
  41. Endo Y, Tsurugi K (1987) RNA N-glycosidase activity of ricin A-chain. Mechanism of action of the toxic lectin ricin on eukaryotic ribosomes. J Biol Chem 262:8128–8130Google Scholar
  42. Endo Y, Mitsui K, Motizuki M, Tsurugi K (1987) The mechanism of action of ricin and related toxic lectins on eukaryotic ribosomes. The site and the characteristics of the modification in 28S ribosomal RNA caused by the toxins. J Biol Chem 262:5908–5912Google Scholar
  43. Engert A, Diehl V, Schnell R, Radszuhn A, Hatwig MT, Drillich S, Schon G, Bohlen H, Tesch H, Hansmann ML, Barth S, Schindler J, Ghetie V, Uhr J, Vitetta E (1997) A phase-I study of an anti-CD25 ricin A-chain immunotoxin (RFT5-SMPT-dgA) in patients with refractory Hodgkin's lymphoma. Blood 89:403–410Google Scholar
  44. Epler K, Padilla D, Phillips G, Crowder P, Castillo R, Wilkinson D, Wilkinson B, Burgard C, Kalinich R, Townson J, Chackerian B, Willman C, Peabody D, Wharton W, Brinker CJ, Ashley C, Carnes E (2012) Delivery of ricin toxin a-chain by peptide-targeted mesoporous silica nanoparticle-supported lipid bilayers. Adv Healthc Mater 1:348–353Google Scholar
  45. Fabbrini MS, Katayama M, Nakase I, Vago R (2017) Plant ribosome-inactivating proteins: progresses, challenges and biotechnological applications (and a few digressions). Toxins (Basel) 9(10):pii: E314. PMID:29023422; PMCID:PMC5666361 Google Scholar
  46. Ferdous AJ, Stembridge NY, Singh M (1998) Role of monensin PLGA polymer nanoparticles and liposomes as potentiator of ricin A immunotoxins in vitro. J Control Release 50:71–78Google Scholar
  47. Ferraz AC, Angelucci MEM, Da Costa ML, Batista IR, de Oliveira BH, da Cunha C (1999) Pharmacological evaluation of ricinine, a central nervous system stimulant isolated from Ricinus communis. Pharmacol Biochem Behav 63:367–375Google Scholar
  48. Ferraz AC, Anselmo-Franci JA, Perosa SR, de Castro-Neto EF, Bellissimo MI, de Oliveira BH, Cavalheiro EA, Naffah-Mazzacoratti MDG, da Cunha C (2002) Amino acid and monoamine alterations in the cerebral cortex and hippocampus of mice submitted to ricinine-induced seizures. Pharmacol Biochem Behav 72:779–786Google Scholar
  49. Fidias P, Grossbard M, Lynch TJ Jr (2002) A phase II study of the immunotoxin N901-blocked ricin in small-cell lung cancer. Clin Lung Vancer 3:219–222Google Scholar
  50. Fodstad O, Olsnes S (1977) Studies on the accessability of ribosomes to inactivation by the toxic lectins abrin and ricin. Eur J Biochem 74:209–215Google Scholar
  51. Fodstad O, Olsnes S, Pihl A (1976) Toxicity, distribution and elimination of the cancerostatic lectins abrin and ricin after parenteral injection into mice. Br J Cancer 34:418–425Google Scholar
  52. Fodstad O, Kvalheim G, Godal A, Lotsberg J, Aamdal S, Host H, Pihl A (1984) Phase I study of the plant protein ricin. Cancer Res 44:862–865Google Scholar
  53. Foxwell BM, Detre SI, Donovan TA, Thorpe PE (1985) The use of anti-ricin antibodies to protect mice intoxicated with ricin. Toxicology 34:79–88Google Scholar
  54. Frankel AE, Laver JH, Willingham MC, Burns LJ, Kersey JH, Vallera DA (1997) Therapy of patients with T-cell lymphomas and leukemias using an anti-CD7 monoclonal antibody-ricin A chain immunotoxin. Leuk Lymphoma 26:287–298Google Scholar
  55. Franz DR (1997) Defense against toxin weapons. In: Sidell FR et al (eds) Textbook of military medicine, part 1: medical aspects of chemical and biological warfare. Office of the Surgeon General, Department of the Army, Washington D.C., pp 603–620Google Scholar
  56. Franz D, Jaax N (1997) Ricin toxin. In: Zajtchuk R, Bellamy RF (eds) Textbook of military medicine: part I, medical aspects of chemical and biological warfare. Office of the Surgeon General of the Army, TMM Publications, Washington, pp 631–642Google Scholar
  57. Fredriksson SÅ, Wunschel DS, Lindström SW, Nilsson C, Wahl K, Åstot C (2018) A ricin forensic profiling approach based on a complex set of biomarkers. Talanta 186:628–635. Google Scholar
  58. Friede MH, von Holt C (1991) Ricin B-chain promotes the internalisation of liposomal contents into rat hepatoma cells. Biochim Biophys Acta 1069:273–280Google Scholar
  59. Friese J, Gleitz J, Gutser UT, Heubach JF, Matthiesen T, Wilffert B, Selve N (1997) Aconitum sp. alkaloids: the modulation of voltage-dependent Na+ channels, toxicity and antinociceptive properties. Eur J Pharmacol 337(2–3):165–174Google Scholar
  60. Frohne D, Pfänder HJ (2004) Giftpflanzen- Ein Handbuch für Apotheker, Ärzte, Toxikologen und Biologen. 5. Auflage. Wissenschaftliche Verlagsgesellschaft mbH, StuttgartGoogle Scholar
  61. Fulton RJ, Uhr JW, Vitetta ES (1988) In vivo therapy of the BCL1 tumor: effect of immunotoxin valency and deglycosylation of the ricin A chain. Cancer Res 48:2626–2631Google Scholar
  62. Funatsu G, Funatsu M (1977) Separation of the two constituent polypeptide chains of ricin D. Agric Biol Chem 41:1211–1215Google Scholar
  63. Furman RR, Grossbard ML, Johnson JL, Pecora AL, Cassileth PA, Jung SH, Peterson BA, Nadler LM, Freedman A, Bayer RL, Bartlett NL, Hurd DD, Cheson BD, Cancer Leukemia Group B, Eastern Cooperative Oncology G (2011) A phase III study of anti-B4-blocked ricin as adjuvant therapy post-autologous bone marrow transplant: CALGB 9254. Leuk Lymphoma 52:587–596Google Scholar
  64. Gage E, Hernandez MO, O'Hara JM, McCarthy EA, Mantis NJ (2011) Role of the mannose receptor (CD206) in innate immunity to ricin toxin. Toxins 3(9):1131–1145. Google Scholar
  65. Gal Y, Mazor O, Falach R, Sapoznikov A, Kronman C, Sabo T (2017) Treatments for pulmonary ricin intoxication: current aspects and future prospects. Toxins 9(10):E311. Google Scholar
  66. Garber EAE (2008) Toxicity and detection of ricin and abrin in beverages. J Food Prot 71:1875–1883Google Scholar
  67. Gardas A, Macpherson I (1979) Microinjection of ricin entrapped in unilamellar liposomes into a ricin-resistant mutant of baby hamster kidney cells. Biochim Biophys Acta 584:538–541Google Scholar
  68. Germer R (1982) Öle, In: Lexikon der Ägyptologie IV, Megiddo-Pyramiden, Hrsg. v. W Helck, Wiesbaden, Sp. 552Google Scholar
  69. Ghalioungui P (1987) The Ebers Papyrus: a new English translation, commentaries, and glossaries. CairoGoogle Scholar
  70. Greenwood JS, Helm M, Gietl C (2005) Ricinosomes and endosperm transfer cell structure in programmed cell death of the nucellus during Ricinus seed development. Proc Natl Acad Sci U S A 102:2238–2243Google Scholar
  71. Griffin T, Rybak ME, Recht L, Singh M, Salimi A, Raso V (1993) Potentiation of antitumor immunotoxins by liposomal monensin. J Natl Cancer Inst 85:292–298Google Scholar
  72. Griffiths GD (2011) Understanding ricin from a defensive viewpoint. Toxins 3(11):1373–1392. Google Scholar
  73. Griffiths GD, Leek MD, Gee DJ (1987) The toxic plant proteins ricin and abrin induce apoptotic changes in mammalian lymphoid tissues and intestine. J Pathol 151:221–229Google Scholar
  74. Griffiths GD, Rice P, Allenby AC, Bailey C, Upshall DG (1995) Inhalation toxicology and histopathology of ricin and abrin toxins. Inhal Toxicol 7(2):269–288. Google Scholar
  75. Griffiths GD, Phillips GJ, Holley J (2007) Inhalation toxicology of ricin preparations: animal models, prophylactic and therapeutic approaches to protection. Inhal Toxicol 19:873–887Google Scholar
  76. Grossbard ML, Lambert JM, Goldmacher VS, Spector NL, Kinsella J, Eliseo L, Coral F, Taylor JA, Blattler WA, Epstein CL et al (1993) Anti-B4-blocked ricin: a phase I trial of 7-day continuous infusion in patients with B-cell neoplasms. J Clin Oncol 11:726–737Google Scholar
  77. Hänsel R, Keller K, Rimpler H, Schneider G (1994) Hagers Handbuch der Pharmazeutischen Praxis: Drogen P-Z Folgeband 2. Springer Verlag Berlin Heidelberg GmbH (Hager's handbook of pharmaceutical practice)Google Scholar
  78. Hartley MR, Lord JM (2004) Cytotoxic ribosome-inactivating lectins from plants. Biochim Biophys Acta 1701:1–14Google Scholar
  79. Hasegawa N, Kimura Y, Oda T, Komatsu N, Muramatsu T (2000) Isolated ricin B-chain-mediated apoptosis in U937 cells. Biosci Biotechnol Biochem 64:1422–1429Google Scholar
  80. Hassan Y, Ogg S, Ge H (2018) Expression of novel fusion antiviral proteins ricin a chain-pokeweed antiviral proteins (RTA-PAPs) in Escherichia coli and their inhibition of protein synthesis and of hepatitis B virus in vitro. BMC Biotechnol 18(1):47. PMID:30081895 PMCID:PMC6080542 Google Scholar
  81. Hauschild F (1960) Pharmakologie und Grundlagen der Toxikologie, 2nd. Thieme, Leipzig, p 568Google Scholar
  82. Hausmann A, Müller GC (2006) The biblical worms on Jonah's Ricinus were Olepa schleini larvae (Lepidoptera, Arctiidae). Mitt Münch Ent Ges 95:5–99 ISSN 0340-4943Google Scholar
  83. He X, McMahon S, Henderson TD II, Griffey SM, Cheng LW (2010) Ricin toxicokinetics and its sensitive detection in mouse sera or feces using immuno-PCR. PLoS One 5.
  84. Henry MA, Lesnick E, Westrum LE, Johnson LR, Canfield RC (1987) Ultrastructure of degenerative changes following ricin application to feline dental pulps. J Neurocytol 16:601–611Google Scholar
  85. Herrera L, Bostrom B, Gore L, Sandler E, Lew G, Schlegel PG, Aquino V, Ghetie V, Vitetta ES, Schindler J (2009) A phase 1 study of Combotox in pediatric patients with refractory B-lineage acute lymphoblastic leukemia. J Pediatr Hematol Oncol 31:936–941Google Scholar
  86. Hu R, Zhai Q, Liu W, Liu X (2001) An insight into the mechanism of cytotoxicity of ricin to hepatoma cell: roles of Bcl-2 family proteins, caspases, ca(2+)-dependent proteases and protein kinase C. J Cell Biochem 81(4):583–593Google Scholar
  87. Hu WG, Yin J, Chau D, Hu CC, Cherwonogrodzky JW (2014) Anti-ricin protective monoclonal antibodies. Ricin Toxin:145–158Google Scholar
  88. Hughes JN, Lindsay CD, Griffiths GD (1996) Morphology of ricin and abrin exposed endothelial cells is consistent with apoptotic cell death. Hum Exp Toxicol 15:443–451Google Scholar
  89. Inns RH, Tuckwell NJ, Bright JE, Marrs TC (1990) Histochemical demonstration of calcium accumulation in muscle fibres after experimental organophosphate poisoning. Hum Exp Toxicol 9:245–250. Google Scholar
  90. Ishiguro M, Funatsu G, Funatsu M (1971a) Biochemical studies on ricin III. Reinvestigation on the purification of lioin. Agr Biol Chem 35:724–728Google Scholar
  91. Ishiguro M, Funatsu G, Funatsu M (1971b) Biochemical studies on ricin IV. Amino acid analysis, carboxyl and amino terminal amino acids of ricin D. Agr Biol Chem 35:729–733Google Scholar
  92. Ishiguro M, Mitarai M, Harada H, Sekine I, Nishimori I, Kikutani M (1983) Biochemical studies on oral toxicity of ricin. I Ricin administered orally can impair sugar absorption by rat small intestine. Chem Pharm Bull (Tokyo) 31:3222–3227Google Scholar
  93. Iversen TG, Frerker N, Sandvig K (2012) Uptake of ricinB-quantum dot nanoparticles by a macropinocytosis-like mechanism. J Nanobiotechnol 10:33Google Scholar
  94. Jang SH, Wientjes MG, Lu D, Au JL (2003) Drug delivery and transport to solid tumors. Pharm Res 20:1337–1350Google Scholar
  95. Johnson RC, Lemire SW, Woolfitt SW, Ospina M, Preston KP, Olson CT et al (2005) Quantification of ricinine in rat and human urine: a biomarker for ricin exposure. J Anal Toxicol 29:149–155Google Scholar
  96. Kalb SR, Barr JR (2009) Mass spectrometric detection of ricin and its activity in food and clinical samples. Anal Chem 81:2037–2042Google Scholar
  97. Kalb SR, Schieltz DM, Becher F, Astot C, Fredriksson SA, Barr JR (2015) Recommended mass spectrometry-based strategies to identify ricin-containing samples. Toxins 7:4881–4894. Google Scholar
  98. Kobert R (1906) Lehrbuch der Intoxikationen, vol 2. Ferdinand Enke, StuttgartGoogle Scholar
  99. Komatsu N, Oda T, Muramatsu T (1998) Involvement of both caspase-like proteases and serine proteases in apoptotic cell death induced by ricin, modeccin, diphtheria toxin, and pseudomonas toxin. J Biochem 124:1038–1044Google Scholar
  100. Korcheva V, Wong J, Corless C, Iordanov M, Magun B (2005) Administration of ricin induces a severe inflammatory response via nonredundant stimulation of ERK, JNK, and P38 MAPK and provides a mouse model of hemolytic uremic syndrome. Am J Pathol 166(1):323–339. Google Scholar
  101. Korcheva V, Wong J, Lindauer M, Jacoby DB, Iordanov MS, Magun B (2007) Role of apoptotic signaling pathways in regulation of inflammatory responses to ricin in primary murine macrophages. Mol Immunol 44(10):2761–2771. Google Scholar
  102. Kumar O, Sugendran K, Vijayaraghavan R (2003) Oxidative stress associated hepatic and renal toxicity induced by ricin in mice. Toxicon: Off J Int Soc Toxinol 41:333–338Google Scholar
  103. Kumar O, Sugendran K, Pant SC, Vijayaraghavan R (2004) Effect of ricin on some biochemical, haematological and histopathological variables. Def Sci J 54:493–502Google Scholar
  104. Lambert JM, Goldmacher VS, Collinson AR, Nadler LM, Blattler WA (1991) An immunotoxin prepared with blocked ricin: a natural plant toxin adapted for therapeutic use. Cancer Res 51:6236–6242Google Scholar
  105. Lappi DA, Kapmeyer W, Beglau JM, Kaplan NO (1978) The disulfide bond connecting the chains of ricin. Proc Natl Acad Sci U S A 75:1096–1100Google Scholar
  106. Laske DW, Muraszko KM, Oldfield EH, DeVroom HL, Sung C, Dedrick RL, Simon TR, Colandrea J, Copeland C, Katz D, Greenfield L, Groves ES, Houston LL, Youle RJ (1997) Intraventricular immunotoxin therapy for leptomeningeal neoplasia. Neurosurgery 41:1039–1049 discussion 1049-1051Google Scholar
  107. LeMaistre CF, Rosen S, Frankel A, Kornfeld S, Saria E, Meneghetti C, Drajesk J, Fishwild D, Scannon P, Byers V (1991) Phase I trial of H65-RTA immunoconjugate in patients with cutaneous T-cell lymphoma. Blood 78:1173–1182Google Scholar
  108. Leshin J, Danielsen M, Credle JJ, Weeks A, O’Connell KP, Dretchen K (2010) Characterization of ricin toxin family members from Ricinus communis. Toxicon 55:658–661Google Scholar
  109. Li C, Yan R, Yang Z, Wang H, Zhang R, Chen H, Wang J (2017) BCMab1-Ra, a novel immunotoxin that BCMab1 antibody coupled to ricin A chain, can eliminate bladder tumor. Oncotarget 8:46704–46705Google Scholar
  110. Li Y, Liu W, Sun C, Zheng M, Zhang J, Liu B, Wang Y, Xie Z, Xu N (2018) Hybrids of carbon dots with subunit B of ricin toxin for enhanced immunomodulatory activity. J Colloid Interface Sci 523:226–233Google Scholar
  111. Lin JY, Liu SY (1986) Studies on the antitumor lectins isolated from the seeds of Ricinus communis (castor bean). Toxicon 24(8):757–765Google Scholar
  112. Lin JY, Tserng KY, Chen CC, Lin LT, Tung TC (1970) Abrin and ricin: new anti-tumour substances. Nature 227(18):292–293Google Scholar
  113. Lin JY, Chang YC, Huang LY, Tung TC (1973) The cytotoxic effects of abrin and ricin on Ehrlich ascites tumor cells. Toxicon: Off J Int Soc Toxinol 11:379–381Google Scholar
  114. Lindauer M, Wong J, Magun B (2010) Ricin toxin activates the NALP3 inflammasome. Toxins (Basel) 2(6):1500–1514. Google Scholar
  115. Ling EA, Wen CY, Shieh JY, Yich TY, Wong WC (1991) Ultrastructural changes of the nodose ganglion cells following an intraneural injection of Ricinus communis agglutin-60 into the vagus nerve in hamsters. J Anat 179:23–32Google Scholar
  116. Lopez Nunez OF, Pizon AF, Tamama K (2017) Ricin poisoning after oral ingestion of castor beans: a case report and review of the literature and laboratory testing. J Emerg Med 53(5):e67–e71. Google Scholar
  117. Lopez MAR, Perez GS, Hernandez CR, Fefer PG, Sanchez MAZ (2010) Activity of Ricinus communis (Euphorbiaceae) against Spodoptera fr ugiperda (Lepidoptera: Noctuidae). Afr J Biotechnol 9:1359–1365Google Scholar
  118. Lord JM, Spooner RA (2011) Ricin trafficking in plant and mammalian cells. Toxins 3:787–801Google Scholar
  119. Lord JM, Roberts LM, Robertus D (1994) Ricin: structure, mode of action, and some current applications. FASEB J 8:201–208Google Scholar
  120. LoRusso PM, Lomen PL, Redman BG, Poplin E, Bander JJ, Valdivieso M (1995) Phase I study of monoclonal antibody-ricin A chain immunoconjugate Xomazyme-791 in patients with metastatic colon cancer. Am J Clin Oncol 18:07–312Google Scholar
  121. Lynch TJ Jr, Lambert JM, Coral F, Shefner J, Wen P, Blattler WA, Collinson AR, Ariniello PD, Braman G, Cook S, Esseltine D, Elias A, Skarin A, Ritz J (1997) Immunotoxin therapy of small-cell lung cancer: a phase I study of N901-blocked ricin. J Clin Oncol 15:723–734Google Scholar
  122. Ma L, Hsu CH, Patterson E, Thadani U, Robinson CP (1996) Ricin depresses cardiac function in the rabbit heart. Toxicol Appl Pharmacol 138(1):72–76. Google Scholar
  123. Madan S, Ghosh PC (1992) Enhancing potency of liposomal monensin on ricin cytotoxicity in mouse macrophage tumor cells. Biochem Int 28:287–295Google Scholar
  124. Madan S, Vasandani VM, Ghosh PC (1993) Potentiation of ricin cytotoxicity by liposomal monensin under in vitro and in vivo conditions. Indian J Biochem Biophys 30:405–410Google Scholar
  125. Magnusson S, Kjeken R, Berg T (1993) Characterization of two distinct pathways of endocytosis of ricin by rat liver endothelial cells. Exp Cell Res 205(1):118–125. Google Scholar
  126. Manjunatha DH, Chua LS (2014) The anti-inflammatory and wound healing properties of honey. Eur Food Res Technol 239(6):1003–1014. Google Scholar
  127. Mensah MB, Awudza JAM, O’Brien P (2018) Castor oil: a suitable green source of capping agent for nanoparticle syntheses and facile surface functionalization. R Soc Open Sci 5:180824. Google Scholar
  128. Messmann RA, Vitetta ES, Headlee D, Senderowicz AM, Figg WD, Schindler J, Michiel DF, Creekmore S, Steinberg SM, Kohler D, Jaffe ES, Stetler-Stevenson M, Chen H, Ghetie V, Sausville EA (2000) A phase I study of combination therapy with immunotoxins IgG-HD37-deglycosylated ricin A chain (dgA) and IgG-RFB4-dgA (Combotox) in patients with refractory CD19(+), CD22(+) B cell lymphoma. Clin Cancer Res 6:1302–1313Google Scholar
  129. Mise T, Funatsu G, Ishiguro M, Funatsu M (1977) Isolation and characterization of ricin E from castor beans. Agric Biol Chem 41(10):2041–2046. Google Scholar
  130. Morlon-Guyot J, Helmy M, Lombard-Frasca S, Pignol D, Pieroni G, Beaumelle B (2003) Identification of the ricin lipase site and implication in cytotoxicity. J Biol Chem 278:17006–17011Google Scholar
  131. Mosinger M (1951) Necrosing or clastic effects of ricin on different organs and on experimental sarcomas. C R Seances Soc Biol Fil 145:412–415Google Scholar
  132. Mutlu H, Meier MAR (2010) Castor oil as a renewable resource for the chemical industry. Eur J Lipid Sci Technol 112:10–30Google Scholar
  133. Muto S, Beevers H (1974) Lipase activities in castor bean endosperm during germination. Plant Physiol 54(1):23–28Google Scholar
  134. Nascimento VV, Castro HC, Abreu PA, Oliveira AEA, Fernandez JH, Araujo JS, Machado OLT (2011) In silico structural characteristics and α-amylase inhibitory properties of Ric c 1 and Ric c 3, allergenic 2s albumins from Ricinus communis seeds. J Agric Food Chem 59:4814–4821. Google Scholar
  135. Neville DM Jr, Youle RJ (1982) Monoclonal antibody-ricin or ricin A chain hybrids: kinetic analysis of cell killing for tumor therapy. Immunol Rev 62:75–91Google Scholar
  136. Nicolson GL, Poste G (1978) Mechanism of resistance to ricin toxin in selected mouse lymphoma cell lines. J Supramol Struct 8:235–245Google Scholar
  137. Noy-Porat T, Alcalay R, Epstein E, Sabo T, Kronman C, Mazor O (2017) Extended therapeutic window for post-exposure treatment of ricin intoxication conferred by the use of high-affinity antibodies. Toxicon 127:100–105. PMID: 28089771Google Scholar
  138. Ogunniyi DS (2006) Castor oil: a vital industrial raw material. Bioresour Technol 97(9):1086–1091Google Scholar
  139. Olaifa JI, Matsumura F, Zeevaart JAD, Mullin CA, Charalambous P (1991) Lethal amounts of ricinine in green peach aphids (Myzus persicae) (Suzler) fed on castor bean plants. Plant Sci 73(2):253–256Google Scholar
  140. Olsnes S (2004) The history of ricin, abrin and related toxins. Toxicon: Off J Int Soc Toxinol 44:361–370Google Scholar
  141. Olsnes S, Pihl A (1973a) Different biological properties of the two constituent peptide chains of ricin, a toxic protein inhibiting protein synthesis. Biochemistry 12(16):3121–3126Google Scholar
  142. Olsnes S, Pihl A (1973b) Isolation and properties of abrin: a toxic protein inhibiting protein synthesis evidence for different biological functions of its two constituent-peptide chains. Eur J Biochem 35:179–185 PMID:4123356Google Scholar
  143. Olsnes S, Saltvedt E, Pihl A (1974) Isolation and comparison of galactose-binding lectins from Abrus precatorius and Ricinus communis. J Biol Chem 249:803–810Google Scholar
  144. Ory RL, Yatsu LY, Kircher HW (1968) Association of lipase activity with the spherosoines of Ricinus communis. Arch Biochem 123:255–264. Google Scholar
  145. Pabis S, Kula J (2016) Synthesis and bioactivity of (R)-ricinoleic acid derivatives: a review. Curr Med Chem 23(35):4037–4056Google Scholar
  146. Patel VR, Dumancas GG, Kasi Viswanath LC, Maples R, Subong BJJ (2016) Castor oil: properties, uses, and optimization of processing parameters in commercial production. Lipid Insights 9:1–12. Google Scholar
  147. Patocka J (2018) Highly toxic ribosome-inactivating proteins as chemical warefare or terrorist agents. Mil Med Sci Lett (Voj Zdrav Listy) 87:1–11 ISSN 0372-7025Google Scholar
  148. Pecot CV, Calin GA, Coleman RL, Lopez-Berestein G, Sood AK (2011) RNA interference in the clinic: challenges and future directions. Nat Rev Cancer 11:59–67Google Scholar
  149. Pittman CT, Guido J, Hamelin EI, Blake TA, Johnson RC (2013) Analysis of a ricin biomarker, ricinine, in 989 individual human urine samples. J Anal Toxicol 37(4):237–240. Google Scholar
  150. Poelchen W, Wirkner K (2003) Ein potenzieller biologischer Kampfstoff. Pharmazeutische Zeitung online (06/2003)Google Scholar
  151. Preijers FW, Tax WJ, De Witte T, Janssen A, vd Heijden H, Vidal H, Wessels JM, Capel PJ (1988) Relationship between internalization and cytotoxicity of ricin A-chain immunotoxins. Br J Haematol 70:289–294Google Scholar
  152. Press OW, Vitetta ES, Farr AG, Hansen JA, Martin PJ (1986) Evaluation of ricin A-chain immunotoxins directed against human T cells. Cell Immunol 102:10–20Google Scholar
  153. Prigent J, Panigai L, Lamourette P, Sauvaire D, Devilliers K et al (2011) Neutralising antibodies against ricin toxin. PLoS One 6(5):e20166.
  154. Ramsden CS, Drayson MT, Bell EB (1989) The toxicity, distribution and excretion of ricin holotoxin in rats. Toxicology 55(1–2):161–171Google Scholar
  155. Rana M, Dhamija H, Prashar B, Sharma S (2012) Ricinus communis L. – a review. Int J Pharmacol Res 4(4):1706–1711Google Scholar
  156. Rao PV, Jayaraj R, Bhaskar AS, Kumar O, Bhattacharya R, Saxena P, Dash PK, Vijayaraghavan R (2005) Mechanism of ricin-induced apoptosis in human cervical cancer cells. Biochem Pharmacol 69:855–865Google Scholar
  157. Rathore SS, Ghosh PC (2008) Effect of surface charge and density of distearylphosphatidylethanolamine-mPEG-2000 (DSPE-mPEG-2000) on the cytotoxicity of liposome-entrapped ricin: effect of lysosomotropic agents. Int J Pharm 350:79–94Google Scholar
  158. Tchou-Wong KM, Roy CJ, Parent C, Cabrera M, Guillemain J, Mac Loughlin R, Levacher E, Fontayne A, Douziech-Eyrolles L, Junqua-Moullet A, Guilleminault L, Thullier P, Guillot-Combe E, Vecellio L, Heuzé-Vourc'h N (2016) Development of a drug delivery system for efficient alveolar delivery of a neutralizing monoclonal antibody to treat pulmonary intoxication to ricin. J Control Release 234:21–32.
  159. Ribeiro BD, Machado de Castro A, Zarur Coelho MA, Guimarães Freire DM (2011) Production and use of lipases in bioenergy: a review from the feedstocks to biodiesel production. Enzym Res:615803.
  160. Robert Koch-Institut (2017) RKI-Ratgeber für Ärzte: Rizin-Intoxikation. Epid Bull 32:315–321. Google Scholar
  161. Roberts LM, Lamb FI, Pappin DJ, Lord JM (1985) The primary sequence of Ricinus communis agglutinin. Comparison with ricin. J Biol Chem 260:15682–15686Google Scholar
  162. RÖMPP Lexikon Chemie, 10. Auflage (1996-1999) Band 2: Cm – G. Herausgegeben von Falbe J, Regitz M. Georg Thieme VerlagGoogle Scholar
  163. Rosenfeld R, Alcalay R, Mechaly A, Lapidoth G, Epstein E, Kronman C, Fleishman SJ, Mazor O (2017) Improved antibody-based ricin neutralization by affinity maturation is correlated with slower off-rate values. Protein Eng Des Sel 30(9):611–617. PMID: 28472478Google Scholar
  164. Roth L, Daunderer M, Kormann K (2008) Giftpflanzen – Pflanzengifte. Vorkommen, Wirkung, Therapie. Allergische und phototoxische Reaktionen, 5. Aufl. HamburgGoogle Scholar
  165. Roxas-Duncan VI, Smith LA (2012) Ricin perspective in bioterrorism, Dr. Stephen Morse (Ed.) ISBN:978-953-51-0205-2Google Scholar
  166. Roy CJ, Hale M, Hartings JM, Pitt L, Duniho S (2003) Impact of inhalation exposure modality and particle size on the respiratory deposition of ricin in BALB/c mice. Inhal Toxicol 15:619–638. Google Scholar
  167. Roy CJ, Song K, Sivasubramani SK, Gardner DJ, Pincus SH (2012) Animal models of ricin toxicosis. Curr Top Microbiol Immunol 357:243–257. Google Scholar
  168. Sandvig K, Skotland T, van Deurs B, Klokk TI (2013) Retrograde transport of protein toxins through the Golgi apparatus. Histochem Cell Biol 140:317–326. Google Scholar
  169. Sausville EA, Headlee D, Stetler-Stevenson M, Jaffe ES, Solomon D, Figg WD, Herdt J, Kopp WC, Rager H, Steinberg SM et al (1995) Continuous infusion of the anti-CD22 immunotoxin IgG-RFB4-SMPT-dgA in patients with B-cell lymphoma: a phase I study. Blood 85:3457–3465Google Scholar
  170. Scarpa A, Guerci A (1982) Various uses of the castor oil plant (Ricinus communis L.): a review. J Ethnopharmacol 5:117–137Google Scholar
  171. 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 154:471–476Google Scholar
  172. Schnell R, Staak O, Borchmann P, Schwartz C, Matthey B, Hansen H, Schindler J, Ghetie V, Vitetta ES, Diehl V, Engert A (2002) A phase I study with an anti-CD30 ricin A-chain immunotoxin (Ki-4.dgA) in patients with refractory CD30+ Hodgkin's and non-Hodgkin's lymphoma. Clin Cancer Res 8:1779–1786Google Scholar
  173. Schnell R, Borchmann P, Staak JO, Schindler J, Ghetie V, Vitetta ES, Engert A (2003) Clinical evaluation of ricin A-chain immunotoxins in patients with Hodgkin's lymphoma. Ann Oncol 14:729–736Google Scholar
  174. Scholl R (2002) Der Papyrus Ebers. Die größte Buchrolle zur Heilkunde Ägyptens, Leipzig (Schriften aus der Universitätsbibliothek Leipzig, 7).Google Scholar
  175. Sehgal P, Khan M, Kumar O, Vijayaraghavan R (2010) Purification, characterization and toxicity profi le of ricin isoforms from castor beans. Food Chem Toxicol 48:3171–3176. Google Scholar
  176. Sehnke PC, Ferl RJ (1999) Processing of preproricin in transgenic tobacco. Protein Expr Purif 15:188–195. Google Scholar
  177. Sehnke PC, Pedrosa L, Paul AL, Frankel AE, Ferl RJ (1994) Expression of active, processed ricin in transgenic tobacco. J Biol Chem 269(36):22473–22476Google Scholar
  178. Selvaggi K, Saria EA, Schwartz R, Vlock DR, Ackerman S, Wedel N, Kirkwood JM, Jones H, Ernstoff MS (1993) Phase I/II study of murine monoclonal antibody-ricin A chain (XOMAZYME-Mel) immunoconjugate plus cyclosporine A in patients with metastatic melanoma. J Immunother Emphasis Tumor Immunol: Off J Soc Biol Ther 13:201–207Google Scholar
  179. Severino LS, Auld DL, Baldanzi M et al (2012) A review on the challenges for increased production of castor. Agron J 104(4):853. Accessed 18 March 2019Google Scholar
  180. Sha O, Yew DT, Ng TB, Yuan L, Kwong WH (2010) Different in vitro toxicities of structurally similar type I ribosome-inactivating proteins (RIPs). Toxicol in Vitro 24(4):1176–1182. Google Scholar
  181. Shaik MS, Ikediobi O, Turnage VD, McSween J, Kanikkannan N, Singh M (2001) Long-circulating monensin nanoparticles for the potentiation of immunotoxin and anticancer drugs. J Pharm Pharmacol 53:617–627Google Scholar
  182. Simmons BM, Stahl PD, Russell JH (1986) Mannose receptor-mediated uptake of ricin toxin and ricin A chain by macrophages. Multiple intracellular pathways for a chain translocation. J Biol Chem 261(17):7912–7920. PMID 3711116Google Scholar
  183. Singh A, Kaur J (2017) Activity of foliage extracts of Ricinus communis L. (Euphorbiaceae) against myiasis causing larvae of Chrysomya bezziana Villeneuvae (Diptera: Calliphoridae). J Vet Med Res 4(1):1070Google Scholar
  184. Singh M, Griffin T, Salimi A, Micetich RG, Atwal H (1994) Potentiation of ricin A immunotoxin by monoclonal antibody targeted monensin containing small unilamellar vesicles. Cancer Lett 84:15–21Google Scholar
  185. Singh M, Ferdous AJ, Kanikkannan N, Faulkner G (2001) Stealth monensin immunoliposomes as potentiator of immunotoxins in vitro. Eur J Pharm Biopharm 52:13–20Google Scholar
  186. Slominska-Wojewodlzka M, Sandvig K (2013) Ricin and ricin-containing immunotoxins: insights into intracellular transport and mechanism of action in vitro. Antibodies 2:236–269Google Scholar
  187. Smallshaw JE, Richardson JA, Pincus S, Schindler J, Vitetta ES (2005) Preclinical toxicity and efficacy testing of RiVax, a recombinant protein vaccine against ricin. Vaccine 23:4775–4784. Google Scholar
  188. Smith DC, Salio M, Lord JM, Roberts LM, Cerundolo V (2004) Lack of dendritic cell maturation by the plant toxin ricin. Eur J Immunol 34(8):2149–2157. Google Scholar
  189. Soler-Rodríguez AM, Ghetie MA, Oppenheimer-Marks N, Uhr JW, Vitetta ES (1993) Ricin A-chain and ricin A-chain immunotoxins rapidly damage human endothelial cells: implications for vascular leak syndrome. Exp Cell Res 206(2):227–234Google Scholar
  190. Sousa NL, Cabral GB, Vieura PM, Balsoni AB, Aragao FJL (2017) Sci Rep 7:15385. Google Scholar
  191. Sparapani M, Buonamici L, Ciani E, Battelli MG, Ceccarelli G, Stirpe F, Contestabile A (1997) Toxicity of ricin and volkensin, two ribosome-inactivating proteins, to microglia, astrocyte, and neuron cultures. Glia 20(3):203–209Google Scholar
  192. Spies JR, Coulson EJ (1964) The chemistry of allergens: XVI. Ion exchange fractionation of the castor bean allegen, CB-1A, and antigenic specificity relationships of the fractions. J Biol Chem 239:1818–1827Google Scholar
  193. Spitler LE, del Rio M, Khentigan A, Wedel NI, Brophy NA, Miller LL, Harkonen WS, Rosendorf LL, Lee HM, Mischak RP et al (1987) Therapy of patients with malignant melanoma using a monoclonal antimelanoma antibody-ricin A chain immunotoxin. Cancer Res 47:1717–1723Google Scholar
  194. Srivastava A, Mathur RM, Prakash R, Agrawal S (2016) Studies on Ricinus lipase enzyme isolated from castor seeds. Orient J Chem 32(2):1235–1247. Google Scholar
  195. Stern D, Skiba M, Kampa B, Worbs S, Dorner BG (2018) Anforderungen an Rizin-Nachweismethoden zur Detektion und Identifizierung aus Verdachtsproben. Toxichem Krimtech 85(3):100Google Scholar
  196. Stillmark H (1888) Ueber Ricin, ein giftiges Fragment aus den Samen von Ricinus comm. L und einigen anderen Euphorbiaceen; PhD Thesis, Kaiserliche Universität zu Dorpat: Tartu, EstoniaGoogle Scholar
  197. Stone MJ, Sausville EA, Fay JW, Headlee D, Collins RH, Figg WD, Stetler-Stevenson M, Jain V, Jaffe ES, Solomon D, Lush RM, Senderowicz A, Ghetie V, Schindler J, Uhr JW, Vitetta ES (1996) A phase I study of bolus versus continuous infusion of the anti-CD19 immunotoxin, IgG-HD37-dgA, in patients with B-cell lymphoma. Blood 88:1188–1197Google Scholar
  198. Streit WJ, Kreutzberg GW (1988) Response of endogenous glial cells to motor neuron degeneration induced by toxic ricin. J Comp Neurol 268(2):248–263. Google Scholar
  199. Tarsio JF, Kelleher PJ, Tarsio M, Emery JM, Lam DM (1997) Inhibition of cell proliferation on lens capsules by 4197X-ricin A immunoconjugate. J Cataract Refract Surg 23(2):260–266Google Scholar
  200. Taubenschmid J, Stadlmann J, Jost M, Klokk TI, Rillahan CD, Leibbrandt A, Mechtler K, Paulson JC, Jude J, Zuber J, Sandvig K, Elling U, Marquardt T, Thiel C, Koerner C, Penninger JM (2017) A vital sugar code for ricin toxicity. Cell Res 27(11):1351–1364. Google Scholar
  201. Taylor S, Massiah A, Lomonossoff G, Roberts LM, Lord JM, Hartley M (1994) Correlation between the activities of five ribosome-inactivating proteins in depurination of tobacco ribosomes and inhibition of tobacco mosaic virus infection. Plant J 5:827–835Google Scholar
  202. Teuscher E, Lindequist U (2010) Biogene Gifte (Biologie-Chemie-Pharmakologie-Toxikologie), Wissenschaftliche Verlagsgesellschaft mbH Stuttgart; 3. Auflage. ISBN 978-3-8047-2438-9Google Scholar
  203. Thiermann H, Zöller L, Szinicz (2013) Chemische und biologische Kampfstoffe. In: Marquardt H, Schäfer SG, Barth H (eds) Toxikologie. Wissenschaftliche Verlagsgesellschaft Stuttgart, 3. Auflage, pp 915–954 ISBN 978-3-8047-2876-9Google Scholar
  204. Thorpe SC, Kemeny DM, Panzani RC, McGurl B, Lord M (1988) Allergy to castor bean II Identification of the major allergens in castor bean seeds. J Allergy Clin Immunol 82:67–72Google Scholar
  205. Timar J, McIntosh DP, Henry R, Cumber AJ, Parnell GD, Davies AJ (1991) The effect of ricin B chain on the intracellular trafficking of an A chain immunotoxin. Br J Cancer 64:655–662Google Scholar
  206. Tokuyama T, Daly J, Witkop B (1969) The structure of batrachotoxin, a steroidal alkaloid from the Colombian arrow poison frog, Phyllobates aurotaenia, and partial synthesis of batrachotoxin and its analogs and homologs. J Am Chem Soc 91(14):3931–3938. Google Scholar
  207. Tong WM, Sha O, Ng TB, Cho EY, Kwong WH (2012) Different in vitro toxicity of ribosome-inactivating proteins (RIPs) on sensory neurons and Schwann cells. Neurosci Lett 524(2):89–94. Google Scholar
  208. Törnquist E, Liu L, Mattsson P, Svensson M (1997) Response of glial cells and activation of complement following motorneuron degeneration induced by toxic ricin. Neurosci Res 28:167–175Google Scholar
  209. Toth RT, Angalakurthi SK, Van Slyke G, Vance DJ, Hickey JM, Joshi SB, Middaugh CR, Volkin DB, Weis DD, Mantis NJ (2017) High-definition mapping of four spatially distinct neutralizing epitope clusters on RiVax, a candidate ricin toxin subunit vaccine. Clin Vaccine Immunol 24(12):e00237–17. Google Scholar
  210. Tunaru S, Althoff TF, Nüsing RM, Diener M, Offermanns S (2012) Castor oil induces laxation and uterus contraction via ricinoleic acid activating prostaglandin E 3 receptors. PNAS.
  211. Tyagi N, Ghosh PC (2011) Folate receptor mediated targeted delivery of ricin entrapped into sterically stabilized liposomes to human epidermoid carcinoma (KB) cells: effect of monensin intercalated into folate-tagged liposomes. Eur J Pharm Sci 43:343–353Google Scholar
  212. Tyagi N, Rathore SS, Ghosh PC (2011) Enhanced killing of human epidermoid carcinoma (KB) cells by treatment with ricin encapsulated into sterically stabilized liposomes in combination with monensin. Drug Deliv 18:394–404Google Scholar
  213. Tyagi N, Rathore SS, Ghosh PC (2013) Efficacy of liposomal monensin on the enhancement of the antitumour activity of liposomal ricin in human epidermoid carcinoma (KB) cells. Indian J Pharm Sci 75:16–22Google Scholar
  214. Tyagi N, Tyagi M, Pachauri M, Ghosh PC (2015) Potential therapeutic applications of plant toxin-ricin in cancer: challenges and advances. Tumour Biol 36:8239–8246Google Scholar
  215. Upasani SM, Kotkar HM, Mendki PS, Maheshwari VL (2003) Partial characterization and insecticidal properties of Ricinus communis L. foliage flavonoids. Pest Manag Sci 59:1349–1354Google Scholar
  216. van Horssen PJ, van Oosterhout YV, de Witte T, Preijers FW (1995) Cytotoxic potency of CD22-ricin A depends on intracellular routing rather than on the number of internalized molecules. Scand J Immunol 41:563–569Google Scholar
  217. Vandenborre G, Smagghe G, Van Damme EJM (2011) Plant lectins as defense proteins against phytophagous insects. Phytochemistry 72:1538–1550. Google Scholar
  218. Vasandani VM, Madan S, Ghosh PC (1992) In vivo potentiation of ricin toxicity by monensin delivered through liposomes. Biochim Biophys Acta 1116:315–323Google Scholar
  219. Verougstraete N, Helsloot D, Deprez C, Heylen O, Casier I, Croes K (2018) Lethal injection of a castor bean extract: ricinine quantification as a marker for ricin exposure using a validated LC-MS/MS method. J Anal Toxicol.
  220. Vieira C, Evangelista S, Cirillo R, Lippi A, Maggi CA, Manzini S (2000) Effect of ricinoleic acid in acute and subchronic experimental models of inflammation. Mediators Inflamm 9(5):223–228. Google Scholar
  221. Vijayan K, Anuradha HJ, Nair CV, Pradeep AR, Awasthi AK, Saratchandra B, Rahman SAS, Singh KC, Chakraborti R, Urs SR (2006) Genetic diversity and differentiation among populations of the Indian eri silkworm, Samia cynthia ricini, revealed by ISSR markers. J Insect Sci 6:30 (online: [])Google Scholar
  222. Vitetta E (2006) Biomedical and biodefense uses for ricin. An original interview. Accessed 01.02.2019, available: from
  223. Vitetta ES, Stone M, Amlot P, Fay J, May R, Till M, Newman J, Clark P, Collins R, Cunningham D et al (1991) Phase I immunotoxin trial in patients with B-cell lymphoma. Cancer Res 51:4052–4058Google Scholar
  224. Vitetta ES, Smallshaw JE, Coleman E et al (2005) A pilot clinical trial of a recombinant ricin vaccine in normal humans. PNAS 103:2268–2273 ISSN (printed): 0027-8424 ISSN (electronic)Google Scholar
  225. Vitetta ES, Smallshaw JE, Coleman E, Jafri H, Foster C, Munford R, Schindler J (2006) A pilot clinical trial of a recombinant ricin vaccine in normal humans. Proc Natl Acad Sci U S A 103:2268–2273Google Scholar
  226. von Fischer-Benzon R (1894) Altdeutsche Gartenflora. Untersuchungen über die Nutzpflanzen des deutschen Mittelalters, ihre Wanderung und ihre Vorgeschichte im klassischen Altertum. Kiel und Leipzig, Verlag von Lipsius & Tischer Accessed 18 March 2019
  227. Vyleta ML, Wong J, Magun BE (2012) Suppression of ribosomal function triggers innate immune signaling through activation of the NLRP3 inflammasome. PLoS One 7(5):e36044. Google Scholar
  228. Wachira SW, Omar S, Jacob JW, Wahome M, Alborn HT, Spring DR et al (2014) Toxicity of six plant extracts and two pyridone alkaloids from Ricinus communis against the malaria vector Anopheles gambiae. Parasit Vectors 7(1):312–319Google Scholar
  229. Waller GR, Skursky L (1972) Translocation and metabolism of ricinine in the castor bean plant, Ricinus communis L. Plant Physiol 50(5):622–626Google Scholar
  230. Watanabe Y, Osawa T (1987) Effect of ricin or ricin A-chain encapsulated in anti-carcinoembryonic antigen (CEA) antibody-bearing liposomes on CEA-producing tumor cells. Chem Pharm Bull 35:740–747Google Scholar
  231. Wawrzynczak EJ, Watson GJ, Cumber AJ, Henry RV, Parnell GD, Rieber EP, Thorpe PE (1991) Blocked and non-blocked ricin immunotoxins against the CD4 antigen exhibit higher cytotoxic potency than a ricin A chain immunotoxin potentiated with ricin B chain or with a ricin B chain immunotoxin. Cancer Immunol Immunother 32(5):289–295Google Scholar
  232. Weber M (2014) The use of ricin abrin or modeccin in the context of criminal or terrorist attacks. Accessed 18 March 2019
  233. Weber M (2018) Bedrohungspotential des Bio-Kampfstoffes Rizin. Toxichem Krimtech 85(3):97–99Google Scholar
  234. Weber M, Schulz H (2011) Immunological detection of ricin and castor seeds in beverages. Food Consum Prod Toxichem Krimtech 78(Special Issue):276Google Scholar
  235. Weller U, Dauzenroth ME, Meyer zu Heringdorf D, Habermann E (1989) Chains and fragments of tetanus toxin. Separation, reassociation and pharmacological properties. Eur J Biochem 182:649–656Google Scholar
  236. Weng X, Wang M, Ge J, Yu S, Liu B, Zhong J, Kong J (2009) Carbon nanotubes as a protein toxin transporter for selective HER2-positive breast cancer cell destruction. Mol BioSyst 5:1224–1231Google Scholar
  237. Westendorf J (2013) Naturstoffe. In: Marquardt H, Schäfer SG, Barth H, Toxikologie. Wissenschaftliche Verlagsgesellschaft Stuttgart, 3. Auflage, 1133. ISBN 978-3-8047-2876-9Google Scholar
  238. Worbs S, Köhler K, Pauly D, Avondet MC, Schaer M, Dorner MB, Dorner BG (2011) Ricinus communis intoxications in human and veterinary medicine-a summary of real cases. Toxins 3(10):1332–1372. Google Scholar
  239. Worbs S, Skiba M, Söderström M, Rapinoja ML, Zeleny R, Russmann H, Schimmel H, Vanninen P, Fredriksson SA, Dorner BG (2015) Characterization of ricin and R. communis agglutinin reference materials. Toxins 7:4906–4934. Google Scholar
  240. Wu YH, Shih SF, Lin JY (2004) Ricin triggers apoptotic morphological changes through caspase-3 cleavage of BAT3. J Biol Chem 279:19264–19275Google Scholar
  241. Wu F, Fan S, Martiniuk F, Pincus S, Muller S, Kohler H, Tchou-Wong KM (2010) Protective effects of anti-ricin A-chain antibodies delivered intracellularly against ricin-induced cytotoxicity. World J Biol Chem 1:188–195Google Scholar
  242. Xu N, Yuan H, Liu W, Li S, Liu Y, Wan J, Li X, Zhang R, Chang Y (2013) Activation of RAW264.7 mouse macrophage cells in vitro through treatment with recombinant ricin toxin-binding subunit B: involvement of protein tyrosine, NF-κB and JAK-STAT kinase signaling pathways. Int J Mol Med 32(3):729–735. Google Scholar
  243. Zahir AA, Rahuman AA, Bagavan A et al (2010) Evaluation of botanical extracts against Haemaphysalis bispinosa Neumann and Hippobosca maculata Leach. Parasitol Res 107(3):585–592. Google Scholar
  244. Zhan J, Zhou P (2003) A simplified method to evaluate the acute toxicity of ricin and ricinus agglutinin. Toxicology 186:119–123Google Scholar
  245. Zhang L, Hsu CH, Robinson CP (1994) Effects of ricin administration to rabbits on the ability of their coronary arteries to contract and relax in vitro. Toxicol Appl Pharmacol 129(1):16–22. Google Scholar
  246. Zhang J, Qin DA, Cheng BX, Ru XQ, Li H, Li L, Yang HP (1999) Preparation, characteristics and toxicity of ricin-containing galactosyl ceramide liposomes. Sheng Wu Hua Xue Yu Sheng Wu Wu Li Xue Bao (Shanghai). Acta biochimica et biophysica Sinica 1999;31(4):472-474.


  1. Final report on the safety assessment of Ricinus communis (Castor) seed oil, hydrogenated castor oil, glyceryl ricinoleate, glyceryl ricinoleate se, ricinoleic acid, potassium ricinoleate, sodium ricinoleate, zinc ricinoleate, cetyl ricinoleate, ethyl ricinoleate, glycol ricinoleate, isopropyl ricinoleate, methyl ricinoleate, and octyldodecyl ricinoleate (2007) Int J Toxicol. 26 Suppl 3:31–77.
  2. Patent (1983) (US 4398937, "Selective algaecides for control of cyanochloronta"(1983 Date of Patent)). Accessed 23 July 2019.
  3. “Giftpflanze des Jahres 2018”; Botanischer Sondergarten Wandsbek:; Accessed 18 March 2019
  4. Clutal Omega:; Accessed 29 March 2019
  5. European Medicines Agency (2012): Assessment report on Viscum album L., herba (2012); EMA/HMPC/246778/2009; Committee on Herbal Medicinal Products (HMPC);Google Scholar

Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Rudolf-Boehm-Institute of Pharmacology and Toxicology, Medical FacultyUniversity of LeipzigLeipzigGermany
  2. 2.Department of HistoryUniversity of LeipzigLeipzigGermany
  3. 3.Rudolf-Boehm-Institute of Pharmacology and Toxicology, Clinical Pharmacology, Medical FacultyUniversity of LeipzigLeipzigGermany

Personalised recommendations