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CBRNE - Ricin

Author: Ferdinando L Mirarchi, DO, Medical Director, Department of Emergency Medicine, Hamot Medical Center; Assistant Clinical Professor, Department of Emergency Medicine, Drexel University School of Medicine
Contributor Information and Disclosures

Updated: Feb 14, 2008

Introduction

Background

Ricin is a potent toxin that has potential to be used as an agent of biological warfare and as a weapon of mass destruction (WMD). Ricin is widely available, easily produced, and derived from the beans of the castor plant (Ricinus communis).

In attempting to evaluate and discuss agents that can be used as WMDs, the question, "What can cause a maximum credible event?" is hopefully answered. A maximum credible event is one that could cause a large loss of life in addition to disruption, panic, and an overwhelming use of civilian healthcare resources. For an agent to be considered capable of causing a maximum credible event, it should be highly lethal, inexpensively and easily produced in large quantities, stable in aerosol form, and have the ability to be dispersed (1-5 µm). The ideal agent also is communicable from person to person and has no treatment or vaccine.

When ricin's characteristics are applied to this model, its use appears limited but should not be underestimated. Ricin is produced easily and inexpensively, is highly toxic, is stable in aerosolized form, and has no treatment or approved vaccine. Its toxicity when compared to living replicating biological agents limits ricin's use. A large amount of ricin is necessary to produce the desired effect of a WMD. For example, the amount of ricin necessary to cover a 100-km² area and cause 50% lethality, assuming aerosol toxicity of 3 mcg/kg and optimum dispersal conditions, is approximately 4 metric tons, whereas only 1 kg of Bacillus anthracis is required. Ricin, however, would have efficacy as a disabling agent. Its use as a food and water contaminant easily could incapacitate many and overwhelm local healthcare resources. Thus, its use as a food and water contaminant is a major concern because of ricin's ease of availability.

Ricin can be disseminated as an aerosol, by injection, or as a food and water contaminant.

Pathophysiology

Ricin is a widely available potential toxin that is produced easily. It is a potent protein derived from the beans of the castor plant (R communis). Castor beans are used in the production of castor oil, a brake and hydraulic fluid constituent. The aqueous phase of the process, termed the "waste mash," is 5-10% ricin. Separating this 66,000-dalton protein requires chromatography, a common undergraduate chemistry skill. Ricin's ease of availability and its lethality make it an attractive agent for use in biological warfare and for potential use as a WMD. Routes of exposure are respiratory (inhaled aerosol), gastrointestinal (GI [ingested]), and parenteral (injected). Clinical manifestations depend on the route of exposure and the amount of absorption.

Ricin is composed of 2 hemagglutinins and 2 toxins. The toxins RCL III and RCL IV are dimers of approximately 66,000 daltons in molecular weight. The toxins have an "A" and a "B" chain, which are polypeptides and joined by a disulfide bond. The B chain binds to cell surface glycoproteins and affects entry into the cell by an unknown mechanism. The A chain acts on the 60S ribosomal subunit and prevents the binding of elongation factor-2. This inhibits protein synthesis and leads to cell death. This basic structure of ricin is similar to those of the botulinum toxin, cholera toxin, diphtheria toxin, tetanus toxin, and insulin.

Frequency

United States

From 1991-1997, 3 cases were related to ricin. In 1991 in Minnesota, 4 members of the Patriots Council, an extremist group that held antigovernment and antitax ideals and advocated the overthrow of the US government, were arrested for plotting to kill a US marshal with ricin.¹ The ricin was produced in a home laboratory. They planned to mix the ricin with the solvent dimethyl sulfoxide (DMSO) and then smear it on the door handles of the marshal's vehicle. The plan was discovered, and the 4 men were convicted. In 1995, a man entered Canada from Alaska on his way to North Carolina.¹ Canadian custom officials stopped the man and found him in possession of several guns, $98,000, and a container of white powder, which was identified as ricin. Lastly, in 1997, a man shot his stepson in the face. Investigators discovered a makeshift laboratory in his basement and found agents such as ricin and nicotine sulfate.

Three US Senate office buildings were closed February 3, 2004, after ricin was found in the mailroom that serves Senate Majority Leader Bill Frist's office. No injuries were reported.

International

In December 2002, 6 terrorist suspects were arrested in Manchester, England; their apartment was serving as a "ricin laboratory."¹ Among them was a 27-year-old chemist who was producing the toxin. Later, on January 5, 2003, British police raided 2 residences around London and found traces of ricin, which led to an investigation of a possible Chechen separatist plan to attack the Russian embassy with the toxin; several arrests were made.²

Mortality/Morbidity

Mortality and morbidity depend on the route and amount of exposure.

• Dermal exposure
  • Dermal exposure of ricin is of little concern because the absorption amount is insignificant.
  • To be absorbed dermally, ricin must be enhanced with a strong solvent such as DMSO.
  • Dermal symptoms depend on the type of solvent and length of exposure. Dermal exposure probably is unable to achieve toxicity.
• Gastrointestinal exposure
  • The LD50 (lethal dose for 50% of exposed population) for GI exposures is 30 mcg/kg.
  • Ricin's lethality is diminished when ingested secondary to poor absorption.
  • In the past, castor bean ingestions were reported to be fatal, but multiple case reports prove otherwise. Many documented cases are related to ingestions of multiple seeds and voluntary ingestion of ricin without fatality.
  • If ingested in sufficient amounts, ricin can cause severe gastroenteritis, GI hemorrhage, and hepatic, splenic, and renal necrosis. Death may occur secondary to circulatory collapse.
• Parenteral exposure
  • Parenteral exposures can be rapidly fatal, with an LD50 similar to aerosol exposure.
  • The highly publicized case of Georgi Markov is evidence of the rapidly fatal nature of parenteral exposure. Markov, an exiled Bulgarian broadcaster, was waiting for a bus in 1978 when he was jabbed with an umbrella in the lower extremity.¹ He then developed severe gastroenteritis and high fevers and died 3 days later. At autopsy, a small 1.5-mm metallic sphere was found at the wound site. It had 2 tiny holes and could hold a volume of 0.28 mm³. No toxin was isolated. Because of the small volume and rapid demise of the patient, ricin was believed to be the only capable inciting agent. The coroner recreated the scenario by injecting a pig with a similar dose of ricin. The pig died in a similar manner 26 hours later.
  • Ricin, if injected, can cause severe local necrosis of muscle and regional lymph nodes with organ involvement and death.
• Aerosol exposure
  • The LD 50 for aerosol exposure is 3 mcg/kg.
  • Aerosol exposure causes weakness, fever, cough, and pulmonary edema within 18-24 hours and severe respiratory distress and death within 36-72 hours.
  • In rodents, aerosol exposure is characterized by necrotizing airway lesions causing tracheitis, bronchitis, bronchiolitis, and interstitial pneumonia with perivascular and alveolar edema.

Clinical

History

• In the case of an isolated attack such as an assassination attempt, no historical markers may be present.
• A victim may relate the pain of an antecedent injection, but this may be overlooked during the history.
• A patient is unlikely to be aware of contamination of ingested foods or beverages.
• If a number of patients are affected simultaneously, by either ingestion or inhalation, the subsequent cluster of patients presenting with similar symptoms over a brief time may alert an astute clinician to the possibility of an intentional act. This is especially true in the case of an inhalation incident (ingestion initially may mimic food poisoning).

Physical

Perform a complete physical examination with any exposure.

• In parenteral exposure, inspect the site for induration, erythema, and the possibility of a retained foreign body. These physical findings may be present prior to or at the time of systemic manifestations.
• In aerosol exposure, the presentation is that of a rapidly progressive acute lung injury, with findings consistent with the stage of progression from a physical examination with normal findings through hypoxia, cyanosis, labored breathing, tachypnea, tachycardia, and progressive respiratory failure.
• In GI exposure, physical examination should be consistent with that for gastroenteritis and volume depletion. If the dose was sufficient and the disease had progressed, frank hematemesis and/or bloody diarrhea or melena may be present.

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