Ricin - it takes so little to get a lethal dose – University of Copenhagen

14 May 2018

Ricin - it takes so little to get a lethal dose

Natural toxin

Accidental and intended intoxications by ricin in humans and animals have been known for centuries. An amount as small as a grain of table salt can be sufficient to kill an adult if it is ingested, inhaled, or injected. It inhibits protein synthesis even if present in extremely small concentrations

Ricin is a highly toxic, naturally occurring protein produced by the plant Ricinus communis (Figure 1). It is a perennial flowering plant species in the spurge family, Euphorbiaceae and contains the toxin ricin within its seeds (Figure 2). Ricinus communis is grown worldwide on an industrial scale for the production of castor oil. Castor bean seeds are used in the production of oil and ricin makes up 3% to 5% of the "waste mash" that is produced during this process.

Ricin is a globular glycoprotein that is composed of different protein chains (Figure 3). The two ricin polypeptide chains have molecular weights of 30 kDa (A) and 33 kDa (B), and are normally linked by a single disulfide bond. It is classified as a Type II ribosome-inactivating protein (RIP). The A chain confers cellular toxicity, while the B chain is essential for cell binding. Once in the target cell, a single ricin molecule can inactivate more than 1500 ribosomes per minute that ultimately resulting in cell death. 

Figure 3. Structure of ricin. The A chain is shown in blue and the B chain in orange

Ricin exerts toxicity by inhibiting protein synthesis. The median lethal dose (LD50) of ricin is around 22 micrograms per kilogram of body weight if the exposure is from injection or inhalation. An estimated lethal oral dose in humans is approximately 1 milligram per kilogram. The large discrepancy in oral and systemic toxicity is likely due to the harsh digestive conditions found in the stomach and epithelium and innate immune barriers present in the intestinal tract. There is no effective treatment available for ricin intoxication and currently investigations are ongoing for possible vaccines and ricin inhibitors. 

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References:

  • He, Xiaohua et al. “Ricin Toxicokinetics and Its Sensitive Detection in Mouse Sera or Feces Using Immuno-PCR.” Ed. Immo A. Hansen. PLoS ONE 5.9 (2010): e12858. PMC. Web. 13 May 2018.
  • Worbs S, Köhler K, Pauly D, et al. Ricinus communis Intoxications in Human and Veterinary Medicine-A Summary of Real Cases. Toxins. 2011;3(10):1332-1372. doi:10.3390/toxins3101332.
  • Sjur Olsnes and Alexander Pihl. Different biological properties of the two constituent peptide chains of ricin a toxic protein inhibiting protein synthesis. Biochemistry 1973 12 (16), 3121-3126. DOI: 10.1021/bi00740a028