Topic Editor: Grant E. Fraser, M.D., FRACGP, FACRRM, ASTEM
Review Date: 3/31/2013
Definition
Ricin is a potent biological toxin derived from the castor bean plant Ricinus communis that is poisonous to humans through accidental or intentional ingestion, inhalation, injection, or dermal/ocular exposure. Ricin primarily induces toxicity by inhibiting protein synthesis with resulting cellular death.
Description
- Ricin is a glycoprotein obtained as a byproduct from the beans of the plant Ricinus communis after the castor oil has been extracted
- When purified, ricin is a water-soluble white powder, stable over a wide pH range, and inactivated at higher temperatures
- The molecular weight of ricin ranges from 60–65 kDa
- Two different polypeptide chains bound together by a disulfide bond make up ricin
- The A-chain (~32 kDa) targets the ribosome, inhibiting protein synthesis, and has been termed a ribosome-inactivating protein (RIP)
- The B-chain (~34 kDa) attaches to cell-surface receptors, and is an galactose/N-acetylgalactosamine-binding lectin
- The primary routes of exposure include ingestion, inhalation, parenteral administration, and dermal/ocular exposure. A much smaller quantity of ricin is required if it is aerosolized or injected
- Dermal exposure is unlikely to result in toxicity and with dimethyl sulfoxide (DMSO) mixed could potentially achieve toxic levels of absorption
- the most lethal of which are inhalation and parenteral routes
- Ricin may be delivered through either aerosol dispersal of particles less than 10 µm (generally 1-5 µm), contamination of food or drink, or direct injection of the solubilized form
- Pathophysiology
- Upon being absorbed, ricin's B-chain attaches to the glycolipids and galactose-containing glycoproteins on cell surfaces and enters the cell via endocytosis
- After endocytosis, ricin further travels through the Golgi apparatus to the endoplasmic reticulum where the disulfide bond between A and B chain is broken. The A chain molecule dislocates into the cytosol where it inactivates eukaryotic ribosomes, thus interrupting cellular protein synthesis with resulting cellular dysfunction and eventual death
- The manifestations of ricin poisoning may mimic gastroenteritis or respiratory diseases
- The approximate lethal oral dose (LD50) for ricin in humans is 30 mcg/kg of body weight (approximately 8 castor beans)
- Inhaled or injected, the LD50 for ricin in humans is 1/10th of that required when ingested (e.g. 3 mcg/kg of body weight)
- Ricin is a potential bioterrorism weapon and has been classified as a Class B biothreat by the Centers for Disease Control and Prevention (CDC). In practicality, it is difficult to deliver and requires significant quantities unless aerosolized or injected
Epidemiology
Incidence/prevalence
- More than 750 documented cases of ricin poisoning in humans have been reported in literature with the majority of clinical cases caused by castor bean ingestion
- Only a single incidence of workers being exposed to particulate matter from castor beans in a castor oil processing facility has been reported
- Use or development of ricin as a biological weapon has been reported in a number of nations starting before World War I
Age
- All age groups are equally at risk of developing ricin toxicity
Gender
- Both genders are equally at risk of developing ricin toxicity
Risk factors
- Accidental or purposeful ingestion of castor beans
- Consumption of food or drink contaminated with ricin
- Individuals involved in castor oil production
- Individuals who are victims of exposures involving ricin aerosolized, ingested or injected
- Individuals with underlying comorbidities such as respiratory or gastrointestinal disease may require a lower level of exposure to result in toxicity or death
Etiology
- The only source of ricin is the castor bean plant Ricinus communis, a perennial shrub of the spurge family Euphorbiaceae . It is a common weed that grows globally in warm climates
- The toxicity of Ricinus communis plant is well known; the seed contains the highest concentration of ricin
- Castor oil is commercially extracted for use as a laxative, lubricant, and in cosmetics
- Castor beans contain about 30% to 35% oil which is extracted using either cold pressing or solvent extraction
- Once the oil is extracted and clarified from the castor beans, ricin can be extracted from the residual mass
- Ricin is virtually absent in castor oil as it does not partition well into oil
- The approximate human lethal dose (LD50) of ricin in is 3 mcg/kg if injected or aerosolized (30 mcg/kg if ingested)
History
- The signs and severity of symptoms of ricin toxicity depend on the route of exposure and the dose
- Initial symptoms may occur in <6 hours following ingestion of ricin and within 8 hours of inhalation
- The symptoms typically progress over a period of 4–36 hours. Patients remaining asymptomatic for 12 hours after exposure have a low likelihood of developing toxicity
- Ingestion
- Bloody diarrhea
- Hematuria
- Hematemesis
- Hallucinations
- Melena
- Nausea
- Persistent vomiting
- Inhalation
- Arthralgia
- Chest tightness
- Cough
- Confusion
- Cyanosis
- Dyspnea
- Fever
- Myalgia
- Nasal congestion
- Nausea
- Profuse sweating
- Thirst
- Weakness
- Injection
- Anorexia
- Fever
- Headache
- Injection site erythema or induration
- Pain and enlarged lymph nodes
- Rigors
- Severe abdominal pain
- Dermal/ocular exposure
- Itchy and watery eyes
- Redness and pain of eyes and skin
- Urticaria
Physical findings on examination
- Ingestion
- Altered mental status
- Decreased skin turgor
- Dilated pupils
- Flat jugular veins
- Hematemesis
- Hypotension
- Melena
- Seizures
- Severe dehydration
- Sore throat
- Inhalation
- Crackles (rales)
- Cyanosis
- Diaphoresis
- Respiratory distress
- Wheezing
- Injection
- Fever
- Hypotension
- Induration at injection site
- Lymphadenopathy
- Tachycardia
- Tachypnea
- Dermal/ocular exposure
- Conjunctivitis
- Skin erythema
Blood Tests findings
Laboratory findings relate to monitoring of the condition (renal/hepatic dysfunction, electrolyte abnormalities), and diagnosis of the condition with specific tests for ricin exposure. It is important to note that many findings will relate to underlying shock and may appear similar to septic shock.
Complete blood count (CBC)
- Nonspecific CBC findings can include leukocytosis and thrombocytopenia
Chemistry
Arterial blood gas
- Arterial blood gas analysis generally shows evidence of metabolic acidosis and hypoxia due to organ dysfunction and on a cellular basis inability to maintain homeostasis due to inhibition of protein synthesis
Other laboratory test findings:
Urinalysis
- Hematuria and myoglobinuria may be detected in urine samples
- A method for measuring the urinary concentration of ricinine, a marker of ricin exposure for up to 48 hours after exposure is available from the CDC
- One study of non-exposed individuals examining ricinine in urinary specimens of 989 individuals found that 1.2% of specimens had measurable levels (range 0.186-4.15 ng/mL). It is important to note that consumer products contain castor bean products which may lead to some level of ricinine in some individuals
Immunological methods
- Enzyme-linked immunosorbent assay (ELISA) allows ricin detection in biological samples for up to 48 hours with a detection limit of ~200 pg/ml, although these assays lack validation and are not available commercially
Other methods
- Other novel methods for detecting ricin in biological samples, such as matrix-assisted laser desorption-ionization mass spectrometry (MALDI-MS), have shown promising results
Other diagnostic test findings
- Various testing methods are available for detection of ricin in environmental samples
- Time-resolved fluorescence immunoassay
- Fiber-optic biosensors utilize fluorescent-labeled anti-ricin IgG antibodies to detect minute quantities of ricin in contaminated samples
- Polymerase chain reaction (PCR)
- PCR may be used to detect and reproduce the genetic portions of the DNA contained in the castor bean plant that specifically produce ricin
Ricin poisoning resembles other poisoning and clinical condition manifestations and requires consideration of this diagnosis in order to differentiate it.
- Ingestion and GI illness
- Localized
- Chemical or Toxin
- Caustic chemicals (corrosives, acids, alkalis)
- Diarrheal shellfish poisoning due to okadaic acid in bivalves
- Medications (e.g., colchicines, salicylates, digoxin)
- Mushrooms (e.g., Boletes species, Lactarius species)
- Plants (e.g., Phytolacca species, solanine-containing plants)
- Simple hydrocarbons
- Strong detergents
- Infectious
- Anisakiasis
- Enterotoxins of Staphylococcus aureus, Bacillus cereus (Type I), and Clostridium perfringens
- Escherichia coli
- Late presentation of enteric pathogens (eg, salmonella, shigella, cholera, Campylobacter jejuni, Yersinia enterocolitica)
- Q fever
- Tularemia
- Multiorgan dysfunction
- Chemical
- Abrin (toxin similar to ricin from the rosary pea plant)
- Certain mushroom species (eg, Amanita phalloides)
- Metals (eg, arsenic, mercury, copper, lead, cadmium, phosgene, others)
- Pharmaceuticals (eg, colchicine, antimetabolite cancer drugs)
- Infectious diseases resulting in sepsis may produce a similar syndrome
- Inhalation and respiratory illness
- Chemicals or toxins
- Abrin (toxin similar to ricin from the rosary pea plant)
- Irritant gases: ozone, chlorine, phosphine, phosgene, oxides of nitrogen
- Metal fume fever
- Paraquat
- Particulate irritants: smoke, fumes, acid mists, dusts
- Polymer fume fever
- Infectious diseases
- Anthrax
- Bacterial or viral agents that cause a diffuse, nonlocalized pneumonic process
- Influenza
- Inhalational tularemia
- Pneumonic plague
- Q fever
- Pulmonary diseases
General treatment items
- No specific antidote or antitoxin therapy has been found useful for ricin poisoning
- Treatment is primarily supportive and varies depending upon the route and severity of the exposure
- In cases of dermal exposure, the patient requires decontamination, with removal of contaminated clothing and jewelry. The area exposure should be thoroughly cleaned, preferably with 0.5% sodium hypochlorite solution (1 part of household bleach with 9 parts of water), or if bleach is not available, copious soap and water. Generally, with dilute bleach, 15 minutes of flushing is adequate and should be followed with simple soap and water washing of the area
- Oral ingestion of ricin should be treated with a single-dose of activated charcoal in non-vomiting patients up to 2 hours after ingestion. Consideration of need for airway protection in highly symptomatic patients may require endotracheal intubation. Gastric lavage may be appropriate in patients presenting within 1 hour of ingestion
- Supportive therapy; particularly with oral ingestion, may require significant fluid resuscitation, and replacement of electrolytes through means of intravenous (IV) fluids
- Inhalational exposure requires supportive treatment, which can include O2 administration in cases of hypoxia, use of bronchodilators with reactive airways, endotracheal intubation with respiratory failure not responding to BiPap or CPAP (bi-level or continuous positive airway pressure)
- Vasopressors such as dopamine or norepinephrine may be needed to treat shock with circulatory collapse in severe cases
Medications indicated with specific doses
Vasopressor agents
- Dopamine [IV]
- Norepinephrine [IV]
AdsorbentsDisposition
- Admission criteria
- Patients with suspected ricin exposure require hospital admission for observation and supportive care
- The clinical progression following ingestion, inhalation, or injection occurs over 4 to 36 hours during which intensive monitoring is essential
- Discharge criteria
- Patients not showing symptoms for 12 hours following exposure have a low likelihood of developing toxicity and generally can safely be discharged with precautions to return if symptoms develop
- Discharged patients have a risk of developing late respiratory symptoms after 20–24 hours. Patients should be advised to present for emergency department review if symptoms occur
Prevention
- The best method to prevent ricin poisoning is avoiding exposure, given that no specific treatment apart from supportive therapy and early decontamination is available
- Emergency response personnel and healthcare providers should take precautions to avoid accidental exposure by utilizing personal protective equipment (PPE) and self-contained breathing apparatus
- Measures to prevent ricin poisoning depend upon the population at risk (military or civilian)
- If ricin arsenals are suspected in the situation of war, military personnel should undertake pre-exposure prevention measures which include physical obstruction of methods of exposure (inhalation, dermal), or chemical detoxification post exposure
- If exposure is unavoidable, inhalation once it occurs is not reversible; ingestion can be treated with lavage or activated charcoal, and dermal exposure can be flushed/washed from the affected areas. Cases of injection may benefit from early surgical excision
- Immunization
- Both active immunization (vaccine) and passive immunization (ricin-specific antibodies) against ricin exposure have been investigated in animal studies, and have shown promising results
- Humans trials are currently underway for RiVax, a recombinant vaccine developed to protect against ricin exposure
- A phase 1 study of RiVax demonstrates an ability to safely induce ricin-protecting antibodies in humans
- Another small phase 1B study demonstrated that antibody titers and neutralizing activity of RiVax could be significantly augmented by adsorbing it on alhydrogel
Prognosis
- If death is going to occur, it generally occurs within 36-72 hours of exposure. Survival is likely if the patient does not succumb within 3–5 days
- Castor bean ingestion has been associated with a mortality rate of 1.9%
- The mortality rate is ~6% in symptomatic patients who are untreated or given limited supportive care
Pregnancy/pediatric effects on condition
- Ricin poisoning in pregnant women is not well documented. Thus, it is difficult to evaluate the adverse effects of ricin exposure on a developing fetus
- As with most conditions in pregnancy, maternal toxicity level relates to impact on a developing fetus
Synonyms/Abbreviations
Ricin toxicity
ICD-9-CM
- 989.89 Toxic effect of other substance, chiefly nonmedicinal as to source, not elsewhere classified
ICD-10
- T57.8X1A Toxic effect of other specified inorganic substances, accidental (unintentional), initial encounter
- T57.8X2A Toxic effect of other specified inorganic substances, intentional self-harm, initial encounter
- T57.8X3A Toxic effect of other specified inorganic substances, assault, initial encounter
