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PLANTS-TOXALBUMINS

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Classification   |    Detailed evidence-based information

Substances Included Synonyms

Therapeutic Toxic Class

    A) The toxalbumins belong to the larger class of plant lectins which refers to plant molecules with a specific affinity for animal cell receptors. The toxalbumins are large (albumin size) molecules with a tertiary structure involving 2 approximately equal size subunits joined with a single disulfide bond.

Specific Substances

    A) ABRUS PRECATORIUS (contains abrin)
    1) Buddhist Rosary Bead
    2) Crab's Eyes
    3) Indian Bead
    4) Indian Licorice Seed
    5) Jequirity Bean
    6) Jungle Bead
    7) Love Bean
    8) Lucky Bean
    9) Mienie-mienie
    10) Ojo de pajaro
    11) Prayer Bead
    12) Rosary Pea
    13) Seminole Bead
    14) Weather Plant
    15) TOXALBUMINS
    16) ABRIN
    17) AGGLUTININ (CONTAINS ABRIN)
    RICINUS COMMUNIS (contains ricin)
    1) Castor Bean Plant (synonym)
    2) Castor Oil Plant
    3) Koll
    4) Mole Bean
    5) Moy Bean
    6) Palma Christi
    7) RICIN
    8) RICININE
    9) RICINE
    ROBINIA PSEUDOACACIA (contains robin and phasin)
    1) Black Acacia
    2) Black Locust
    3) Phasin
    4) ROBIN
    HURA CREPITANS
    1) Sandbox tree
    JATROPHA CURCAS
    1) Barbados nut
    2) Curcas bean
    3) Physic nut
    4) Purge nut
    JATROPHA GOSSYPIFOLIA
    1) Bellyache bush
    JATROPHA HASTATA
    1) Perrigrina
    JATROPHA MACROHIZA
    1) Devil's Potato
    JATROPHA MULTIFIDA
    1) Coral Plant
    2) Physic nut

Available Forms Sources

    A) SOURCES
    1) TOXALBUMINS - Several genetically unrelated plants including the black locust (Robina pseudoacacia), castor bean (Ricinus communis), European mistletoe (Viscum album), and jequirity bean (Abrus precatorius) contain chemically similar high molecular weight glycoproteins (toxalbumins).
    B) USES
    1) ABRUS PRECATRIUS - A series of poisonings from beaded jewelry using the rosary pea in the Boston area resulted in banning such jewelry (Hart, 1963).
    2) ORDEAL POISON - The seeds of this plant were used as an ordeal poison in Africa and Madagascar (Hart, 1963).
    3) HERBAL - Its irritating properties were use to treat trachoma. Cold infusions were placed on the conjunctiva. It was also used to decrease corneal opacities. Because of serious side effects, it is no longer used (Hart, 1963).
    4) NON-MEDICAL - RICIN has been used as a chemical warfare agent (Budavari, 1989), a reagent for pepsin and trypsin (Sax & Lewis, 1987), an experimental antitumor and immunosuppressive agent (HSDB , 1990), and as a commercial mole killer (Hayes, 1982).

Overview

Life Support

    A) This overview assumes that basic life support measures have been instituted.

Clinical Effects

    0.2.1) SUMMARY OF EXPOSURE
    A) USES: Plants containing toxalbumins grow in the wild (mainly in tropical areas) or are used for ornamental purposes (mostly in warmer areas). Seeds (abrin) of Abrus precatorius are brightly colored and used for decorative purposes (eg, bracelets or necklaces). The beans from Ricinus communis (ricin) are a commercial source of castor oil and the remaining powder (pomace) is used as a fertilizer. Castor oil and its derivatives, which are used in a variety of products and extracted from the seeds of the castor plant, have ricin removed as part of the purification process. In addition, the Jatorpha species contain poisonous seeds; the toxin, jatorphin, is a plant lectin (toxalbumin) related to ricin. There are concerns that ricin might be used as a chemical warfare agent.
    B) TOXICOLOGY: RICIN: Ricin is a protein consisting of 2 approximately equal in size subunits (A and B) bound by disulfide bonds. The B part of the toxin binds to galactose containing receptors in the cell wall, allowing the intact ricin protein to be actively transported into a cell. The A part then inhibits protein synthesis by disabling the 60S ribosomal units. Disruption of protein synthesis inhibition is considered the primary mode of toxicity. Other mechanisms that may contribute include activation of apoptotic pathways, direct cell membrane damage, and release of cytokine inflammatory mediators. ABRIN: Abrin, a toxalbumin that can be found in the seeds of the Abrus precatorius plant acts via a similar mechanism and function to ricin. However, abrin is considered more potent.
    C) EPIDEMIOLOGY: Exposures in the United States are very uncommon, and severe manifestations are even rarer.
    D) WITH POISONING/EXPOSURE
    1) OVERDOSE: INGESTION: MILD TO MODERATE TOXICITY: CASTOR BEANS or ABRUS SEEDS: Significant toxicity is not expected after ingestion of intact or whole seeds. Nausea, vomiting, diarrhea and abdominal pain may develop. SEVERE TOXICITY: CASTOR BEARS or ABRUS SEEDS: The majority of patients that ingest castor beans or abrus precatorius seeds recover with supportive care. However, there have been reports of severe toxicity. Nausea, vomiting and diarrhea generally develop within hours of severe overdose, and may lead to volume depletion and hypotension. Severe irritation of the GI mucosa may develop, which may result in gastrointestinal hemorrhage and sloughing of tissue. Electrolyte abnormalities may occur. Fever may develop early. Severe exposures may ultimately result in death, reflecting the severe cytotoxic effects of the toxins to the liver, central nervous system, and kidneys. ABRUS PRECATORIUS: Other systemic effects such as hepatic and renal damage, decreased mental status, coma and seizures may be delayed several days after ingestion of Abrus precatorius seeds. INHALATION EXPOSURE: Inhalation exposure to toxalbumins is generally mild. Castor beans do contain an allergen protein that may cause an asthma-like reaction in susceptible individuals. Poison by inhalation of ricin can in rare cases cause systemic symptoms such as fevers and arthralgias and can proceed to respiratory distress and death. DERMAL EXPOSURE: Dermal exposures are generally mild and are due to allergens in the parent plants rather than toxalbumins. EYE EXPOSURE: It may result in mild irritation. PARENTERAL EXPOSURE: Parenteral exposures are very rare and usually intentional. In one case, local tissue necrosis from a ricin injection may have potentiated a bacterial infection. Clandestine injection of a pellet filled with ricin caused a high fever within a few hours, an elevated white count, hypotension and hypothermia, and death 3 days after the original injury.
    0.2.3) VITAL SIGNS
    A) WITH POISONING/EXPOSURE
    1) FEVER may be the major and presenting clinical feature; hypotension may also be observed.
    0.2.4) HEENT
    A) EYES: Both miosis and mydriasis have been reported. Retinal hemorrhages may be seen in poisoning. Application of abrin to the eyes may result in mild irritation to loss of eye tissue, depending on the concentration.
    0.2.5) CARDIOVASCULAR
    A) Fast, weak pulse is common. No direct cardiotoxic effects are generally seen. Shock due to fluid and electrolyte loss may occur.
    0.2.6) RESPIRATORY
    A) Castor beans contain an allergen protein that has caused various asthma-like reactions.
    0.2.9) HEPATIC
    A) Liver damage may occur in serious overdoses. Disturbances in carbohydrate metabolism may occur if liver function deteriorates.
    B) Other hepatic enzymes may also be increased, such as ALT, total bilirubin, AST, alkaline phosphatase, and GGT.
    0.2.10) GENITOURINARY
    A) Hematuria is often seen. Serum creatinine may be elevated.
    0.2.13) HEMATOLOGIC
    A) Toxalbumins are hemagglutinating. Effects in poisoning are minimal, even though the effect is prominent in vitro.
    0.2.20) REPRODUCTIVE
    A) No specific toxicities have been noted in pregnancy of humans. Abrin has been used by herbalists as an abortifacient.
    B) Birth defects and seizures were reported in an infant born to a young mother who had taken castor oil seed (Ricinus commuis) orally as a contraceptive for 8 weeks after conception.

Laboratory Monitoring

    A) Monitor vital signs and mental status.
    B) Monitor serum electrolytes, renal function, and liver enzymes in symptomatic patients.
    C) Laboratory radioimmunoassay is available to measure ricin levels after ingestion, however, specific ricin concentrations are neither readily available nor useful in guiding therapy.

Treatment Overview

    0.4.2) ORAL/PARENTERAL EXPOSURE
    A) MANAGEMENT OF MILD TO MODERATE TOXICITY
    1) Significant toxicity is not expected after ingestion of intact or whole seeds (ie, castor bean, abrus precatorius seeds). Management of mild to moderate toxicity requires only good supportive care. Treatment may include volume resuscitation for vomiting and diarrhea, and electrolyte restoration for abnormalities.
    B) MANAGEMENT OF SEVERE TOXICITY
    1) Severe toxicity may require more aggressive treatment, including intubation and the use of pressors for hypotension. Treat seizures with benzodiazepines, add propofol or barbiturates, if seizures persist.
    C) INHALATION EXPOSURE
    1) Move patient to fresh air and observe for respiratory distress, and treat symptomatic patients as necessary with supplemental oxygen, inhaled beta adrenergic agonists, or intubation.
    D) DERMAL EXPOSURE
    1) Remove contaminated clothing and wash exposed area thoroughly with soap and water.
    E) EYE EXPOSURE
    1) Irrigate exposed eyes with copious amounts of water or normal saline for at least 15 minutes, removing contact lenses first if the patient wears them. If the patient continues to have irritation, pain, swelling, lacrimation, or photophobia after eye wash, a more detailed ophthalmologic exam should be performed.
    F) PARENTERAL EXPOSURE
    1) Parenteral exposure may be very difficult to detect. Local excision of injected ricin toxin as soon as possible after exposure may prevent or alleviate systemic effects.
    G) DECONTAMINATION
    1) PREHOSPITAL: Decontamination is generally not necessary if the seeds were known to have been swallowed intact without chewing. Prehospital use of activated charcoal should be considered if the patient is not already vomiting and the ingestion is recent (within the last hour), or if there will be a delay in transport to a healthcare facility of an hour or more. Contraindications of activated charcoal include a depressed mental status that might lead to a compromised airway, seizures, or other comorbidities that might be adversely affected by induced emesis.
    2) DERMAL or EYE EXPOSURE: Decontaminate by washing the skin or irrigating the eyes.
    3) HOSPITAL: Decontamination is generally not necessary if seeds are known to have been swallowed intact without chewing. Administer activated charcoal, if the ingestion is relatively recent (within the past hour) and the patient is able to protect their airway. Gastric lavage may also be considered for a relatively recent or very large ingestion that has occurred within the past hour. There is no evidence for the use of additional doses of activated charcoal. Whole bowel irrigation with polyethylene glycol solution might be considered for ingestions of multiple seeds, especially if the patient presents more than an hour after ingestion, but it has not been studied.
    H) AIRWAY MANAGEMENT
    1) In mild to moderate toxicity, airway management is unlikely to be an issue. However, patients with more severe toxicity may exhibit depressed mental status or other symptoms that may require intubation.
    I) ANTIDOTE
    1) There is no specific antidote available.
    J) ENHANCED ELIMINATION
    1) Due to their large molecular size (ricin: 66 kilodaltons; abrin: 65 kilodaltons), hemodialysis is unlikely to be useful, although charcoal hemoperfusion may adsorb circulating toxalbumins (although there is no reported clinical experience with this method). There is also no evidence for the use of urinary alkalinization or multiple dose activated charcoal to enhance toxin elimination.
    K) PATIENT DISPOSITION
    1) HOME CRITERIA: Asymptomatic patients who have inadvertently ingested intact seeds without chewing can be monitored at home. Patients with deliberate ingestions and those who have chewed the seeds should be referred to a healthcare facility.
    2) OBSERVATION CRITERIA: All symptomatic patients those with intentional ingestions, and those who have swallowed chewed or broken seeds (ie, castor bean or abrus precatorius seeds) should be sent to a healthcare facility for observation until they are clearly improved or asymptomatic. Of note, most patients with significant toxicity develop GI effects within 6 to 12 hours, but more severe manifestations may develop for 1 to 5 days. If a patient is asymptomatic after 12 hours, they may be discharged; however, the patient should be instructed to return to the hospital if symptoms develop after that period.
    3) ADMISSION CRITERIA: All symptomatic patients should be admitted. Depending on the severity of illness, a patient may require an ICU admission. Criteria for discharge from the hospital should include either resolution of all symptoms or clear improvement from the toxicity.
    4) CONSULT CRITERIA: Consult a medical toxicologist or poison center for any patient with symptoms of a significant exposure. Consultation from law enforcement may be needed if there is a history of exposure to purified ricin. For intentional self-harm exposures, a psychiatric consult is necessary.
    L) PITFALLS
    1) The most difficult issue in managing these patients may be in making the diagnosis. Assays for detection for toxalbumin exposure exists, but are not readily available. Thus, a careful initial history and investigation is necessary in making the diagnosis.
    M) TOXICOKINETICS
    1) There is extremely limited data available concerning the toxicokinetics of toxalbumins in humans. Oral absorption is poor. The half-life of ricin was 2 days in one patient. Most patients with significant toxicity develop GI effects within 6 to 12 hours, but more severe manifestations may develop for 1 to 5 days.
    N) PREDISPOSING CONDITIONS
    1) Patients at extremes of age or in poor health may be more sensitive to the toxic effects of toxalbumins.
    O) DIFFERENTIAL DIAGNOSIS
    1) The differential diagnosis can include certain mushroom poisonings, organophosphate toxicity, and other causes of severe gastrointestinal symptoms.

Range Of Toxicity

    A) SUMMARY: Minimal toxicity is expected, if the beans are swallowed intact without chewing. Ricin is considered among one of the most toxic compounds known to man. It is theorized that a single castor bean may be severely toxic and even lethal to a child. Different estimates have been made for the minimal lethal dose to adults and may be influenced by a number of variables, such as the qualities (eg, size and weight) of the castor beans ingested, as well as the patient's own comorbidities.
    B) CASTOR BEANS: These beans contain approximately 1% to 10% of ricin. Estimates for minimal lethality include 8 to 10 castor beans or 30 mg up to 1 mg/kg for an adult. However, there are case reports of children ingesting 2 or more castor beans and adults ingesting up to 30 castor beans with survival, though they did have symptoms of gastroenteritis.
    C) RICIN INJECTION: An injection of less than 3 mcg/kg of ricin is thought to be able to cause death.
    D) ABRIN: The abrin content in a single Abrus precatorius seed is approximately 0.15%. Though there is a case report of death following ingestion of a single bean, there are also reports of survival after ingestion of multiple abrin beans.

Clinical Effects

Heent

    3.4.1) SUMMARY
    A) EYES: Both miosis and mydriasis have been reported. Retinal hemorrhages may be seen in poisoning. Application of abrin to the eyes may result in mild irritation to loss of eye tissue, depending on the concentration.
    3.4.3) EYES
    A) WITH POISONING/EXPOSURE
    1) CASTOR BEAN: MYDRIASIS has been reported (Balint, 1974).
    2) CASTOR BEAN: MIOSIS was seen in 3 of 4 patients in one report (Malizia et al, 1977).
    a) ABRUS PRECATORIUS: Miosis occurred in a 42-year-old man after ingesting Abrus precatorius seeds (white with black eye) (Pillay et al, 2005)
    b) JATROPHA MULTIFIDA: Miosis occurred in 4 siblings after eating the fruit of Jatropha multifida plant (Koltin et al, 2006).
    3) ABRUS PRECATORIUS: PAPILLEDEMA was observed in a teenager and an adult after intentionally ingesting up to 10 crushed seeds of Abrus precatorius. Each patient also had manifestations of raised intracranial pressure. On admission, one patient was stuporous with multiple episodes of seizures; she died 4 days after ingestion. The other patient recovered completely after several weeks of intensive supportive care (Subrahmanyan et al, 2008).
    4) CONJUNCTIVITIS: Instillation into the eye produces a dose-related irritation which ranges from mild conjunctivitis to loss of substance from the eye itself (Hart, 1963).
    5) CASTOR BEAN: OPTIC NERVE INJURY has been reported (Balint, 1974).
    6) RETINAL HEMORRHAGES may be seen in cases of intoxication (Hart, 1963).
    3.4.6) THROAT
    A) IRRITATION of the oropharynx may result from direct exposure to the toxalbumins, especially abrin (Kingsbury, 1964; Hart, 1963).

Cardiovascular

    3.5.1) SUMMARY
    A) Fast, weak pulse is common. No direct cardiotoxic effects are generally seen. Shock due to fluid and electrolyte loss may occur.
    3.5.2) CLINICAL EFFECTS
    A) HYPOTENSIVE EPISODE
    1) WITH POISONING/EXPOSURE
    a) CASTOR BEAN: No direct cardiac toxicity has been attributed to toxalbumins. Cardiovascular shock, the usual cause of death, seems to be related to fluid imbalance, rather than to any direct cardiovascular action (Challoner & McCarron, 1990).
    b) CASTOR BEAN: Symptoms usually begin within 12 hours after ricin ingestion. These are nonspecific and may include nausea, vomiting, diarrhea, and abdominal pain. The clinical effects may progress to hypotension, liver failure, renal dysfunction and death due to multiorgan failure or cardiovascular collapse (Audi et al, 2005).
    c) CASTOR BEAN: CASE REPORT: A 42-year-old man was admitted with epigastric pain, nausea and vomiting after ingesting a herbal mixture containing a large amount of ricin bean powder to treat constipation. His initial laboratory studies showed evidence of a coagulopathy, followed by elevated liver enzymes and renal failure. Hypotension was present throughout his hospital course despite the use of inotropic agents. On day 3, the patient died of a cardiopulmonary arrest that did not respond to resuscitation efforts (Assiri, 2012).
    B) CARDIOVASCULAR FINDING
    1) CASTOR BEAN: BETA BLOCKADE: A slight beta blockade effect has been reported (Balint, 1974).
    C) TACHYCARDIA
    1) WITH POISONING/EXPOSURE
    a) Pulse is often weak and rapid, in both animal and human poisonings (Hui et al, 2004; Sullivan & Chavez, 1981; Lampe & Fagerstrom, 1968; Emery, 1887).

Summary Of Exposure

    A) USES: Plants containing toxalbumins grow in the wild (mainly in tropical areas) or are used for ornamental purposes (mostly in warmer areas). Seeds (abrin) of Abrus precatorius are brightly colored and used for decorative purposes (eg, bracelets or necklaces). The beans from Ricinus communis (ricin) are a commercial source of castor oil and the remaining powder (pomace) is used as a fertilizer. Castor oil and its derivatives, which are used in a variety of products and extracted from the seeds of the castor plant, have ricin removed as part of the purification process. In addition, the Jatorpha species contain poisonous seeds; the toxin, jatorphin, is a plant lectin (toxalbumin) related to ricin. There are concerns that ricin might be used as a chemical warfare agent.
    B) TOXICOLOGY: RICIN: Ricin is a protein consisting of 2 approximately equal in size subunits (A and B) bound by disulfide bonds. The B part of the toxin binds to galactose containing receptors in the cell wall, allowing the intact ricin protein to be actively transported into a cell. The A part then inhibits protein synthesis by disabling the 60S ribosomal units. Disruption of protein synthesis inhibition is considered the primary mode of toxicity. Other mechanisms that may contribute include activation of apoptotic pathways, direct cell membrane damage, and release of cytokine inflammatory mediators. ABRIN: Abrin, a toxalbumin that can be found in the seeds of the Abrus precatorius plant acts via a similar mechanism and function to ricin. However, abrin is considered more potent.
    C) EPIDEMIOLOGY: Exposures in the United States are very uncommon, and severe manifestations are even rarer.
    D) WITH POISONING/EXPOSURE
    1) OVERDOSE: INGESTION: MILD TO MODERATE TOXICITY: CASTOR BEANS or ABRUS SEEDS: Significant toxicity is not expected after ingestion of intact or whole seeds. Nausea, vomiting, diarrhea and abdominal pain may develop. SEVERE TOXICITY: CASTOR BEARS or ABRUS SEEDS: The majority of patients that ingest castor beans or abrus precatorius seeds recover with supportive care. However, there have been reports of severe toxicity. Nausea, vomiting and diarrhea generally develop within hours of severe overdose, and may lead to volume depletion and hypotension. Severe irritation of the GI mucosa may develop, which may result in gastrointestinal hemorrhage and sloughing of tissue. Electrolyte abnormalities may occur. Fever may develop early. Severe exposures may ultimately result in death, reflecting the severe cytotoxic effects of the toxins to the liver, central nervous system, and kidneys. ABRUS PRECATORIUS: Other systemic effects such as hepatic and renal damage, decreased mental status, coma and seizures may be delayed several days after ingestion of Abrus precatorius seeds. INHALATION EXPOSURE: Inhalation exposure to toxalbumins is generally mild. Castor beans do contain an allergen protein that may cause an asthma-like reaction in susceptible individuals. Poison by inhalation of ricin can in rare cases cause systemic symptoms such as fevers and arthralgias and can proceed to respiratory distress and death. DERMAL EXPOSURE: Dermal exposures are generally mild and are due to allergens in the parent plants rather than toxalbumins. EYE EXPOSURE: It may result in mild irritation. PARENTERAL EXPOSURE: Parenteral exposures are very rare and usually intentional. In one case, local tissue necrosis from a ricin injection may have potentiated a bacterial infection. Clandestine injection of a pellet filled with ricin caused a high fever within a few hours, an elevated white count, hypotension and hypothermia, and death 3 days after the original injury.

Respiratory

    3.6.1) SUMMARY
    A) Castor beans contain an allergen protein that has caused various asthma-like reactions.
    3.6.2) CLINICAL EFFECTS
    A) BRONCHOSPASM
    1) WITH POISONING/EXPOSURE
    a) CASTOR BEAN: ASTHMA: Pulmonary sensitization and asthma-like reactions were seen on continued exposure to the pumace remaining after castor oil extraction, and when burlap bags that contained castor beans were reused (Bernton, 1973; Brugsch, 1960).
    B) TOXIC INHALATION INJURY
    1) WITH POISONING/EXPOSURE
    a) Poison by inhalation of ricin has been reported (Kacnelson, 1960). Inhalation exposure symptom onset is usually within 8 hours. Symptoms usually seen are cough, dyspnea, arthralgias, and fever. The patient's clinical picture may progress to respiratory distress and death. Other organ system manifestations may not be observed (Audi et al, 2005).
    C) ACUTE LUNG INJURY
    1) WITH POISONING/EXPOSURE
    a) In one patient who developed adult respiratory distress syndrome (ARDS), tracheal aspirate fluid showed protein content the same as serum, suggesting a high capillary permeability (Snodgrass, 1982).

Neurologic

    3.7.2) CLINICAL EFFECTS
    A) CENTRAL NERVOUS SYSTEM DEFICIT
    1) WITH POISONING/EXPOSURE
    a) SUMMARY: Somnolence and loss of consciousness have been reported with toxalbumin exposure (Sahni et al, 2007; Lampe & Fagerstrom, 1968; Emery, 1887).
    b) ABRUS PRECATORIUS: Coma with depressed deep tendon reflexes and down-going plantar reflexes occurred in a 42-year-old man after ingesting Abrus precatorius seeds (white with black eye) (Pillay et al, 2005).
    c) JATROPHA MULTIFIDA: After eating the fruit of Jatropha multifida plant, 2 of 4 siblings became mildly obtunded (Koltin et al, 2006). In another exposure, 2 young boys were noted to be obtunded and mildly disoriented approximately 90 minutes after ingesting a large amount of fruit (approximately 10 each) from the J. multifida plant. Recovery was complete following aggressive fluid and electrolyte replacement (Levin et al, 2000).
    B) ENCEPHALITIS
    1) WITH POISONING/EXPOSURE
    a) ABRUS PRECATORIUS: A 30-year-old woman developed bloody diarrhea, epigastric pain, vomiting, and deep coma (a Glasgow Coma Score of 5 [E1M3V1]) 7 to 8 hours after ingesting 3 to 4 seeds of a plant called "ratti" (jequirity pea - Abrus precatorius). The examination of the right eye showed pupillary dilatation with downwards deviations, suggestive of third nerve palsy. She also experienced two episodes of generalized seizures in the hospital. Laboratory results revealed hepatic and renal toxicity. MRI brain scan showed altered signal intensity in bilateral peritrigonal, parieto-occipital white matter, external and internal capsules, and lentiform nuclei, suggestive of demyelination. She was diagnosed with acute demyelinating encephalitis. Her condition deteriorated further and she died 3 days later (Sahni et al, 2007).
    C) RAISED INTRACRANIAL PRESSURE
    1) WITH POISONING/EXPOSURE
    a) ABRUS PRECATORIUS: CASE REPORTS: Two women ingested up to 10 seeds of Abrus precatorius and had evidence of raised intracranial pressure and papilledema. One patient recovered normal sensorium, 3 weeks after intensive supportive care (including mannitol, dexamethasone and acetazolamide) with no permanent sequelae. The other patient died after developing stupor and seizures, 4 days after ingestion (Subrahmanyan et al, 2008).
    D) HEADACHE
    1) WITH POISONING/EXPOSURE
    a) CASE SERIES: In one case series (n=20), approximately 40% of Indian children (age range 8 to 13) developed headache, 30 minutes to 2 hours after ingesting 1 to 4 Jatropha Curcas nuts (Kulkarni et al, 2005).
    E) SEIZURE
    1) WITH POISONING/EXPOSURE
    a) Seizures have been reported in animal studies, but have been reported infrequently in humans (Frohne & Pfander, 1984; Hart, 1963). Muscle fasciculations may appear (Lampe & Fagerstrom, 1968).
    b) ABRUS PRECATORIUS: However, seizures have been documented in several cases reports of Abrus precatorius seed ingestion (Subrahmanyan et al, 2008; Sahni et al, 2007; Pillay et al, 2005).
    c) ABRUS PRECATORIUS: Seizures and altered sensorium occurred in a 42-year-old man after ingesting Abrus precatorius seeds (white with black eye) (Pillay et al, 2005).
    d) ABRUS PRECATIORIUS: Seizures occurred in a 30-year-old woman after ingesting 3 to 4 seeds of a plant called "ratti" (jequirity pea - Abrus precatorius) (Sahni et al, 2007).
    F) OPTIC NEURITIS
    1) WITH POISONING/EXPOSURE
    a) NERVE EFFECTS: Optic nerve damage has been reported with ricin. Hypoglossal and vagus nerves, binding and transporting ricin, suggests specific receptors in neural tissue (Helke et al, 1985).

Gastrointestinal

    3.8.2) CLINICAL EFFECTS
    A) HEMORRHAGIC DIARRHEA
    1) WITH POISONING/EXPOSURE
    a) TOXALBUMINS: Frequent stools, including bloody diarrhea and tenesmus, are well known signs of toxalbumin toxicity (Pillay et al, 2005; Malizia et al, 1977; Kopferschmitt et al, 1983).
    b) CASTOR BEAN: Diarrheal fluids are commonly heme positive and may be grossly bloody within 3 hours (Spyker et al, 1982).
    c) Dehydration may result from diarrhea (Ingle et al, 1966) (Wedin et al, 1986).
    B) GASTROINTESTINAL TRACT FINDING
    1) WITH POISONING/EXPOSURE
    a) SUMMARY: Vomiting and abdominal pain are frequently reported symptoms (Sahni et al, 2007; Levin et al, 2000; Aplin & Eliseo, 1997; Palatnick & Tenenbein, 2000).
    b) ONSET: Symptoms usually begin within 12 hours after ricin ingestion. These are nonspecific and may include nausea, vomiting, diarrhea, and abdominal pain. The clinical effects may progress to hypotension, liver failure, renal dysfunction, and death due to multiorgan failure or cardiovascular collapse (Audi et al, 2005).
    c) INCIDENCE: In one study, all 57 exposures developed vomiting and diarrhea (Ingle et al, 1966).
    1) CASE SERIES: In a Philippine study of Jatropa ingestions, 64% developed vomiting and 52% had abdominal pain; 98% were discharged 24 to 48 hours post exposure (Makalinao, 1993).
    2) CASE SERIES: In a case series of 20 Indian children (age 8 to 13 years), vomiting, abdominal pain, and diarrhea occurred in 95%, 25%, and 50% of children, respectively, 30 minutes to 2 hours after ingesting 1 to 4 Jatropha Curcas nuts. Approximately 5% of children were asymptomatic. Following supportive therapy, all patients recovered completely within 6 hours (Kulkarni et al, 2005).
    d) CASTOR BEAN or ABRUS: POTENTIAL SEVERITY: The severity of an exposure is often dependent on the degree of mastication of the seeds which contain the toxalbumins (Kinamore et al, 1980). Symptoms may be delayed for several days (Brugsch, 1960).
    e) CASTOR BEAN: EPIDEMIOLOGY: Reed (1998) reported that in South Africa it is not unusual to find a clustering of cases of toxic gastroenteritis among young children who ingest the seeds of the castor oil plant (ricinus communis). It is suggested that the unique marbled pattern appearance of the seeds may be very attractive to children, and that the multiple seeds found in the pod are shared (Reed, 1998).
    f) CASE SERIES
    1) CASTOR BEAN SEED
    a) A retrospective, observational review was conducted by the California Poison Control Centers from 2001 to 2011 to determine the characteristics of castor bean seed (Ricinus communis) exposure, serious morbidity and mortality were not reported and there were no reports of delayed symptoms. Gastrointestinal symptoms were the most common (59 cases (67%) clinical finding. Ingesting 10 or more seeds was likely to result in gastrointestinal symptoms compared to those ingesting 10 or less seeds (odds ratio 7.5 (95% Confidence Interval). In one case, nausea and diarrhea occurred after ingesting 6 ground castor bean seeds with complete recovery in 24 hours. Another patient ingested 10 chewed castor bean seeds and developed gastrointestinal symptoms (ie, nausea, vomiting, diarrhea, and abdomina pain) and recovered after 8 days; laboratory studies remained normal. Hematochezia and vomiting occurred in a patient that intentionally ingested and injected castor bean seed extract requiring hospital admission for 2 days with complete recovery. In all cases, symptoms were self-limited (Thornton et al, 2014).
    g) CASE REPORTS
    1) ADULTS
    a) CASTOR BEAN: Vomiting was noted 3 hours after ingesting 30 castor bean seeds in a 21-year-old (Kopferschmitt et al, 1983).
    b) CASTOR BEAN: Vomiting was seen an hour after ingesting 12 castor beans in a 26-year-old (Spyker et al, 1982).
    2) ABRUS PRECATORIUS: Bloody diarrhea and abdominal pain occurred in 2 patients after ingesting Abrus precatorius seeds (Sahni et al, 2007; Pillay et al, 2005).
    3) JATROPHA MULTIFIDA: Watery diarrhea and protracted vomiting developed in 4 siblings after eating the fruit of Jatropha multifida plant (Koltin et al, 2006). In another exposure, 2 healthy boys (age 9.5 years and 8.5 years) developed intractable vomiting, colicky abdominal pain and watery diarrhea 90 minutes after ingesting large amounts of fruit (approximately 10 pieces each) from a Jatropha multifida plant. The children recovered following aggressive fluid and electrolyte replacement and urine alkalization (Levin et al, 2000).
    4) CASE REPORT: An 8-year-old boy began vomiting repeatedly approximately 2.5 hours after chewing on a piece of bark from the Black Locust (Robinia pseudoacacia) tree. He also developed tachycardia (114 bpm), an elevated alkaline phosphatase level (183 units/L), and a increased white blood cell count (18.4 x 10(3)/L). The patient's vomiting resolved and his white blood cell count normalized with supportive care. He was discharged approximately 5 days postingestion, despite persistent elevation of his alkaline phosphatase level (251 units/L) (Hui et al, 2004).

Hepatic

    3.9.1) SUMMARY
    A) Liver damage may occur in serious overdoses. Disturbances in carbohydrate metabolism may occur if liver function deteriorates.
    B) Other hepatic enzymes may also be increased, such as ALT, total bilirubin, AST, alkaline phosphatase, and GGT.
    3.9.2) CLINICAL EFFECTS
    A) INJURY OF LIVER
    1) WITH POISONING/EXPOSURE
    a) CARBOHYDRATE METABOLISM: Deterioration in liver function with resulting disturbances in carbohydrate metabolism are somewhat like diabetes mellitus (Balint, 1978). Histochemically, injuries seem to be mainly of the smooth endoplasmic reticulum and depletion of liver glycogen.
    b) CASTOR BEAN: LIVER FAILURE: Symptoms usually begin within 12 hours after ricin ingestion. These are nonspecific and may include nausea, vomiting, diarrhea, and abdominal pain. The clinical effects may progress to hypotension, liver failure, renal dysfunction and death due to multiorgan failure or cardiovascular collapse (Audi et al, 2005).
    c) ABRUS PRECATORIUS: Hepatotoxicity (serum alanine aminotransferase 400 Units/L; bilirubin 2 mg/dL, alkaline phosphatase 10 Units/L) occurred in a 30-year-old woman 7 to 8 hours after ingesting 3 to 4 seeds of a plant called "ratti" (jequirity pea - Abrus precatorius) (Sahni et al, 2007).
    B) LIVER ENZYMES ABNORMAL
    1) WITH POISONING/EXPOSURE
    a) ABRUS PRECATORIUS: Elevations of liver enzymes have been documented due to Jequirity Bean poisoning (Niyogi, 1977) and following ingestion of ricin bean powder (Assiri, 2012). Transient signs of liver damage were noted in children who ingested from 0.5 to 6 seeds (Kaszas & Papp, 1960). Elevations of liver enzymes were also reported in 2 young boys who ingested the fruit of a Jatropha multifida plant, which completely resolved upon follow-up at 3 weeks (Levin et al, 2000).
    b) CASTOR BEAN: CASE REPORT: A 42-year-old man developed elevated liver enzymes 2 days after ingesting a large amount of castor bean powder for the treatment of constipation. Despite treatment measures, the patient died on day 3 of a cardiopulmonary arrest (Assiri, 2012).
    c) CASTOR BEAN: CASE REPORT: Delayed evidence of laboratory liver dysfunction at 72 hours (ALT 51 Units/L, AST 150 Units/L, alkaline phosphatase 912 Units/L, total bilirubin 14 mg/dL, and GGT 101 Units/L) occurred in a 20-month-old female who ate the contents of a package of castor beans (the actual number of seeds unknown) (Palatnick & Tenenbein, 2000). Labs were within normal limits one month later.
    d) CASE REPORT: An 8-year-old boy began vomiting repeatedly approximately 2.5 hours after chewing on a piece of bark from the Black Locust (Robinia pseudoacacia) tree. He also developed tachycardia (114 bpm), an elevated alkaline phosphatase level (183 units/L), and a increased white blood cell count (18.4 x 10(3)/L). The patient's vomiting resolved and his white blood cell count normalized with supportive care. He was discharged approximately 5 days postingestion, despite persistent elevation of his alkaline phosphatase level (251 units/L) (Hui et al, 2004).

Genitourinary

    3.10.1) SUMMARY
    A) Hematuria is often seen. Serum creatinine may be elevated.
    3.10.2) CLINICAL EFFECTS
    A) SERUM CREATININE RAISED
    1) WITH POISONING/EXPOSURE
    a) CASTOR BEAN: A transiently elevated serum creatinine was the only GU effect noted with ricin (Wedin et al, 1986). Mild proteinuria, acetonuria, and azotemia were reported after castor bean ingestion (Malizia et al, 1977).
    b) ABRUS PRECATORIUS: Elevated creatinine levels (1.6 mg/dL) occurred in a 42-year-old man after ingesting Abrus precatorius seeds (white with black eye) (Pillay et al, 2005).
    c) CASTOR BEAN: Elevated creatinine (150 Unitsmol/L {normal: up to 123 Unitsmol/L}) and urea levels were observed in a patient following the ingestion of an herbal mixture containing ricin bean powder. He also presented with elevated liver enzymes and a coagulopathy. Hypotension persisted throughout his hospital course despite inotropic therapy. On day 3, he died of a cardiopulmonary arrest (Assiri, 2012).
    B) ABNORMAL RENAL FUNCTION
    1) WITH POISONING/EXPOSURE
    a) SUMMARY: Symptoms usually begin within 12 hours after ricin ingestion. These are nonspecific and may include nausea, vomiting, diarrhea, and abdominal pain. The clinical effects may progress to hypotension, liver failure, renal dysfunction and death due to multiorgan failure or cardiovascular collapse (Audi et al, 2005).
    b) ABRUS PRECATORIUS: Renal toxicity (blood urea 89 mg/dL, serum creatinine 3 mg/dL) occurred in a 30-year-old woman 7 to 8 hours after ingesting 3 to 4 seeds of a plant called "ratti" (jequirity pea - Abrus precatorius) (Sahni et al, 2007).
    C) BLOOD IN URINE
    1) WITH POISONING/EXPOSURE
    a) CASTOR BEANS: Microscopic hematuria and cylindruria were noted briefly 5 days after an 8-year-old ingested 12 castor beans (Malizia et al, 1977). A urinalysis may be grossly bloody with many red cells but no casts (Spyker et al, 1982).
    b) ABRUS PRECATORIUS: Mild proteinuria and occasional RBCs were detected in urinalysis of a 42-year-old man after he ingested Abrus Precatorius seeds (white with black eye) (Pillay et al, 2005).

Acid-Base

    3.11.2) CLINICAL EFFECTS
    A) ACIDOSIS
    1) WITH POISONING/EXPOSURE
    a) MINIMAL EFFECT: Major acid-base difficulties are not characteristic of toxalbumin poison.
    b) Lactate and pyruvate concentrations may rise. However, the lactic to pyruvate proportion is preserved.

Hematologic

    3.13.1) SUMMARY
    A) Toxalbumins are hemagglutinating. Effects in poisoning are minimal, even though the effect is prominent in vitro.
    3.13.2) CLINICAL EFFECTS
    A) BLOOD COAGULATION DISORDER
    1) WITH POISONING/EXPOSURE
    a) CASTOR BEAN: CASE REPORT: A 42-year-old man was admitted with epigastric pain, nausea and vomiting after ingesting a herbal mixture containing ricin bean powder. His initial laboratory studies showed evidence of a coagulopathy (ie, prothrombin time 19 second {control 12 seconds} and a prolonged activated partial thromboplastin time, 56 seconds {control 32 seconds}), followed by elevated liver enzymes and renal failure. Hypotension was present throughout his hospital course despite the use of inotropic agents. On day 3, the patient died of a cardiopulmonary arrest that did not respond to resuscitation efforts (Assiri, 2012).
    B) ERYTHROCYTE AGGLUTINATION
    1) WITH POISONING/EXPOSURE
    a) CASTOR BEAN: Hemagglutination is seen in animal and laboratory work (Waller et al, 1966), but is almost never seen in actual poisonings (Jelinikova & Vesely, 1960; Corwin, 1961).
    b) CASTOR BEAN: Intravascular aggregation (sludge formation) of red cells was produced experimentally with ricin within 60 minutes of exposure (Balint, 1974).
    c) It is now known that the hemagglutinating agent is not ricin, but another lectin (sometimes called ricine) (Lin & Li, 1980).
    C) LEUKOCYTOSIS
    1) WITH POISONING/EXPOSURE
    a) JATROPHA MULTIFIDA: After eating the fruit of Jatropha multifida plant, 4 siblings developed leukocytosis (23.4 x 10(9)/L; 18.8 x 10(9)/L; 25.4 x 10(9)/L; 22.8 x 10(9)/L) (Koltin et al, 2006).

Dermatologic

    3.14.2) CLINICAL EFFECTS
    A) DERMATITIS
    1) WITH POISONING/EXPOSURE
    a) SUMMARY: Skin eruptions are not often seen with toxalbumins.
    b) LOCUST: An erythematous eruption is described after exposure to locust bark (Emery, 1887).
    c) JATROPHA MULTIFIDA: Allergic dermatitis may occur following contact with these plants, which contain allergenic glycoproteins (Levin et al, 2000).
    B) HYPERSENSITIVITY REACTION
    1) WITH POISONING/EXPOSURE
    a) CASTOR BEAN: Sensitization to castor bean (IgE response) may occur, with the main allergen being a 25 storage albumin (proposed name Ric cI) (Thorpe et al, 1988a; Thorpe et al, 1988b). Both Type 1 (immediate) and Type IV (delayed) reactions have been reported in industrial settings (Kanerva et al, 1990).
    1) CASTOR BEAN: Shivering without fever was reported in one case where 30 castor beans were ingested (Kopferschmitt et al, 1983).
    b) ZINC RICINOLEATE: This chemical has been used in deodorants, and been shown to be a sensitizer and to produce rashes in individuals (Dooms-Goossens et al, 1987).
    C) CELLULITIS
    1) WITH POISONING/EXPOSURE
    a) CASTOR BEAN: A 53-year-old man chewed 13 castor beans and subcutaneously injected himself in the inner thigh with the masticated product in a suicide attempt. He subsequently developed cellulitis at the injection site that progressively spread to the back of the lower leg. Enterococcus faecalis was the bacterium isolated from the pus and the necrotic tissues. The patient recovered following parenteral antibiotic administration and debridement of the necrotic tissue (Passeron et al, 2004). It is believed that the initial tissue necrosis was due to ricin found in the castor beans and that ricin also acted as a cofactor for the pathogenicity of the bacterium resulting in E. faecalis infection.

Musculoskeletal

    3.15.2) CLINICAL EFFECTS
    A) FATIGUE
    1) WITH POISONING/EXPOSURE
    a) MALAISE and general weakness are associated with toxalbumin poisoning.

Immunologic

    3.19.2) CLINICAL EFFECTS
    A) ACUTE ALLERGIC REACTION
    1) WITH POISONING/EXPOSURE
    a) CASTOR BEAN: Ricin is an antigen. Castor bean powder is an allergic problem in handlers (Lindenbaum, 1966).
    b) TOXALBUMINS: The toxalbumins are NOT known to have an acute or chronic immunostimulation or suppression effect.
    c) JATROPHA species in a particular J. multifida contain allergenic glycoproteins that may cause anaphylaxis (Levin et al, 2000).
    d) CASTOR BEANS: Various parts of the plant are known allergens (Saragea et al, 1966).
    1) CASTOR BEAN: POLLEN: An allergic reaction to castor bean pollen which included sneezing, lacrimation, itching, rhinorrhea, cough, and wheezing, has been described (Lindenbaum, 1966).
    2) CASTOR BEAN OR POMACE: Intense respiratory irritation, eye irritation, itching and burning of the nose, and wheals and blisters have been seen as an allergic reaction to castor bean pomace (Bernton, 1945), or castor beans (Robbins, 1923).
    3) ANAPHYLAXIS was reported in one case where a castor bean on a necklace was crushed and the powder inadvertently rubbed into the patient's eyes (Lockey & Dunkelberger, 1969).

Reproductive

    3.20.1) SUMMARY
    A) No specific toxicities have been noted in pregnancy of humans. Abrin has been used by herbalists as an abortifacient.
    B) Birth defects and seizures were reported in an infant born to a young mother who had taken castor oil seed (Ricinus commuis) orally as a contraceptive for 8 weeks after conception.
    3.20.2) TERATOGENICITY
    A) SKELETAL MALFORMATION
    1) Moderate growth retardation, craniofacial dysmorphia, absence deformity of limbs, vertebral segmentation defect, and seizures were described in an infant born to a young mother who had taken castor oil seed (Ricinus commuis) orally as a contraceptive for 8 weeks after conception (El Mauhoub et al, 1983).
    3.20.3) EFFECTS IN PREGNANCY
    A) ABORTION
    1) Abrin has been used by herbalists as an abortifacient (Hart, 1963).
    B) LACK OF EFFECT
    1) No specific toxicities have been noted in pregnancy of humans.
    3.20.4) EFFECTS DURING BREAST-FEEDING
    A) BREAST MILK
    1) Toxalbumins probably do not appear in breast milk.
    2) MILK STIMULATION - Castor beans have found wide use, both systemically and topically, in stimulating breast milk production in many countries.

Vital Signs

    3.3.1) SUMMARY
    A) WITH POISONING/EXPOSURE
    1) FEVER may be the major and presenting clinical feature; hypotension may also be observed.
    3.3.3) TEMPERATURE
    A) FEVER may be the major and presenting clinical feature (Pillay et al, 2005; Knight, 1979). Ricin, and presumably the other toxalbumins, has an pyrogenic effect in animals (Balint, 1974).
    B) CASE SERIES: In one case series (n=20), approximately 40% of Indian children (age range 8 to 13) developed fever, 30 minutes to 2 hours after ingesting 1 to 4 Jatropha Curcas nuts (Kulkarni et al, 2005).
    3.3.4) BLOOD PRESSURE
    A) Hypotension may occur due to fluid loss.
    3.3.5) PULSE
    A) Tachycardia may occur due to fluid loss.

Laboratory Monitoring

Monitoring Parameters Levels

    4.1.1) SUMMARY
    A) Monitor vital signs and mental status.
    B) Monitor serum electrolytes, renal function, and liver enzymes in symptomatic patients.
    C) Laboratory radioimmunoassay is available to measure ricin levels after ingestion, however, specific ricin concentrations are neither readily available nor useful in guiding therapy.
    4.1.2) SERUM/BLOOD
    A) BLOOD/SERUM CHEMISTRY
    1) Careful attention should be given to fluid and electrolyte balance, and hepatic enzymes.
    2) GLUCOSE METABOLISM - Major alterations in glucose metabolism occur in experimental ricin intoxication. Glycogen stores decrease, gastrointestinal absorption of glucose decreases, and glucose concentrations fall. Blood sugar values are expected to fall (Malizia et al, 1977; Lampe, 1976).
    3) OTHER LABORATORY: Urea nitrogen, amino acid hydrogen, and inorganic phosphate levels may rise. Serum aspartate, alanine aminotransferases, total bilirubin, alkaline phosphatase, GGT, and lactate dehydrogenase would be expected to rise (Malizia et al, 1977; Frohne & Pfander, 1984) (Palatnick & Tenenbein, 1997).
    B) HEMATOLOGIC
    1) Monitor hematologic parameters.

Methods

    A) IMMUNOASSAY
    1) Immunologic methods are available for detection of ricin. These include a radioimmunoassay and an enzyme linked immunosorbent assay (ELISA) (Godal et al, 1981; Godal et al, 1984). These are not widely available nor of any clinical importance.
    B) GAS CHROMATOGRAPHY/MASS SPECTROMETRY and LIQUID CHROMATOGRAPHY
    1) Darby et al (2001) were able to use mass spectrometry successfully as a screening tool, and to provide presumptive identification of samples containing the alkaloid ricinine by GC/MS and LC/MS. The authors suggested that these methods were both rapid and reliable in correctly identifying the ricin toxin; and the methods could be a complementary technique for the identification and determination of castor bean extract(s) (Darby et al, 2001).
    C) TANDEM MASS SPECTROMETRY
    1) McGrath et al (2011) developed a mass-spectrometry based method to detect ricin in beverages (ie, tap water, milk, apple juice and orange juice). Absolute quantification was performed using isotope dilution mass spectrometry with a linear ion trap. This method allows for the identification of ricin A chain and B chain and for distinction of ricin from ricin agglutinin. The limit of detection was 0.64 ng/mL (10 fmol/mL) (McGrath et al, 2011).
    D) BIOASSAY
    1) A bioassay using the Chinese hamster ovary cell assay was described by Spyker et al (1982) and could be used in detecting ricin in body fluids. There is also a mouse toxicity and a Vero cell cytotoxicity test (Wannemacher et al, 1991).
    E) IMMUNOCHROMATOGRAPHIC TEST
    1) A rapid, simple, immunochromatographic test was developed to detect ricin with a sensitivity of 1 ng ricin/mL which can be read with the naked eye. It is intended for the rapid diagnosis of an aerosolized ricin poisoning using nasal swabs of exposed individuals. The antibodies used in the test are specific for ricin A chain. It purportedly has limited cross reactivity with other lectins, its range can extend to 10 mcg/mL with a plateau from 10 to at least 250 mcg/mL with no "hook effect" (no decrease in the signal with increasing concentrations of antigen) (Guglielmo-Viret et al, 2007).
    F) OTHER
    1) Panzani & Johansson (1986) reported a radio-allergo-sorbent test (RAST) demonstrated a 95% correlation with skin test in 41 patients with known sensitivity to castor bean and a 97% correlation in 49 patients with no contact, a remote contact, or a close contact with castor bean. This in vitro test may offer a risk-free diagnostic alternative to skin testing for potent allergens (Panzani & Johansson, 1986).

Treatment

Life Support

    A) Support respiratory and cardiovascular function.

Patient Disposition

    6.3.1) DISPOSITION/ORAL EXPOSURE
    6.3.1.1) ADMISSION CRITERIA/ORAL
    A) All symptomatic patients should be admitted. Depending on the severity of illness, a patient may require an ICU admission. Criteria for discharge from the hospital should include either resolution of all symptoms or clear improvement from the toxicity.
    6.3.1.2) HOME CRITERIA/ORAL
    A) Asymptomatic patients who have inadvertently ingested intact seeds without chewing can be monitored at home. Patients with deliberate ingestions and those who have chewed the seeds should be referred to a healthcare facility.
    6.3.1.3) CONSULT CRITERIA/ORAL
    A) Consult a medial toxicologist or poison center for any patient with symptoms of a significant exposure. Consultation from law enforcement may be needed if there is a history of exposure to purified ricin. For intentional self-harm exposures, a psychiatric consult is necessary.
    6.3.1.5) OBSERVATION CRITERIA/ORAL
    A) All symptomatic patients those with intentional ingestions, and those who have swallowed chewed or broken seeds (ie, castor bean or abrus precatorius seeds) should be sent to a healthcare facility for observation until they are clearly improved or asymptomatic. Of note, most patients with significant toxicity develop GI effects within 6 to 12 hours, but more severe manifestations may develop for 1 to 5 days. If a patient is asymptomatic after 12 hours, they may be discharged; however, the patient should be instructed to return to the hospital if symptoms develop after that period.
    1) CASTOR BEAN SEED
    a) A retrospective, observational review was conducted by the California Poison Control Centers from 2001 to 2011 to determine the characteristics of castor bean seed (Ricinus communis) exposure, serious morbidity and mortality were not reported and there were no reports of delayed symptoms. Gastrointestinal symptoms were the most common (59 cases (67%)) clinical finding. Ingesting 10 or more seeds was likely to result in gastrointestinal symptoms compared to those ingesting 10 or less seeds (odds ratio 7.5 (95% Confidence Interval)). In one case, nausea and diarrhea occurred after ingesting 6 ground castor bean seeds with complete recovery in 24 hours. Another patient ingested 10 chewed castor bean seeds and developed gastrointestinal symptoms (ie, nausea, vomiting, diarrhea, and abdomina pain) and recovered after 8 days; laboratory studies remained normal. Hematochezia and vomiting occurred in a patient that intentionally ingested and injected castor bean seed extract requiring hospital admission for 2 days with complete recovery. Of the 22 (26%) cases, requiring hospital admission the median length of stay was 2 days (range, 1 to 10 days) and the median number of seeds ingested was 8.5 seeds (range, 1 to 20 seeds). In most cases, patient's admitted to chewing the seeds. However, symptoms were self-limited in all cases (Thornton et al, 2014).

Monitoring

    A) Monitor vital signs and mental status.
    B) Monitor serum electrolytes, renal function, and liver enzymes in symptomatic patients.
    C) Laboratory radioimmunoassay is available to measure ricin levels after ingestion, however, specific ricin concentrations are neither readily available nor useful in guiding therapy.

Oral Exposure

    6.5.1) PREVENTION OF ABSORPTION/PREHOSPITAL
    A) SUMMARY
    1) Decontamination is generally not necessary if the seeds were known to have been swallowed intact without chewing. Prehospital use of activated charcoal should be considered if the patient is not already vomiting and the ingestion is recent (within the last hour), or if there will be a delay in transport to a healthcare facility of an hour or more. Contraindications of activated charcoal include a depressed mental status that might lead to a compromised airway, seizures, or other comorbidities.
    B) ACTIVATED CHARCOAL
    1) PREHOSPITAL ACTIVATED CHARCOAL ADMINISTRATION
    a) Consider prehospital administration of activated charcoal as an aqueous slurry in patients with a potentially toxic ingestion who are awake and able to protect their airway. Activated charcoal is most effective when administered within one hour of ingestion. Administration in the prehospital setting has the potential to significantly decrease the time from toxin ingestion to activated charcoal administration, although it has not been shown to affect outcome (Alaspaa et al, 2005; Thakore & Murphy, 2002; Spiller & Rogers, 2002).
    1) In patients who are at risk for the abrupt onset of seizures or mental status depression, activated charcoal should not be administered in the prehospital setting, due to the risk of aspiration in the event of spontaneous emesis.
    2) The addition of flavoring agents (cola drinks, chocolate milk, cherry syrup) to activated charcoal improves the palatability for children and may facilitate successful administration (Guenther Skokan et al, 2001; Dagnone et al, 2002).
    2) CHARCOAL DOSE
    a) Use a minimum of 240 milliliters of water per 30 grams charcoal (FDA, 1985). Optimum dose not established; usual dose is 25 to 100 grams in adults and adolescents; 25 to 50 grams in children aged 1 to 12 years (or 0.5 to 1 gram/kilogram body weight) ; and 0.5 to 1 gram/kilogram in infants up to 1 year old (Chyka et al, 2005).
    1) Routine use of a cathartic with activated charcoal is NOT recommended as there is no evidence that cathartics reduce drug absorption and cathartics are known to cause adverse effects such as nausea, vomiting, abdominal cramps, electrolyte imbalances and occasionally hypotension (None Listed, 2004).
    b) ADVERSE EFFECTS/CONTRAINDICATIONS
    1) Complications: emesis, aspiration (Chyka et al, 2005). Aspiration may be complicated by acute respiratory failure, ARDS, bronchiolitis obliterans or chronic lung disease (Golej et al, 2001; Graff et al, 2002; Pollack et al, 1981; Harris & Filandrinos, 1993; Elliot et al, 1989; Rau et al, 1988; Golej et al, 2001; Graff et al, 2002). Refer to the ACTIVATED CHARCOAL/TREATMENT management for further information.
    2) Contraindications: unprotected airway (increases risk/severity of aspiration) , nonfunctioning gastrointestinal tract, uncontrolled vomiting, and ingestion of most hydrocarbons (Chyka et al, 2005).
    6.5.2) PREVENTION OF ABSORPTION
    A) ACTIVATED CHARCOAL
    1) Decontamination is generally not necessary if seeds are known to have been swallowed intact without chewing. Administer activated charcoal, if the ingestion is relatively recent (within the past hour) and the patient is able to protect their airway.
    2) CHARCOAL ADMINISTRATION
    a) Consider administration of activated charcoal after a potentially toxic ingestion (Chyka et al, 2005). Administer charcoal as an aqueous slurry; most effective when administered within one hour of ingestion.
    3) CHARCOAL DOSE
    a) Use a minimum of 240 milliliters of water per 30 grams charcoal (FDA, 1985). Optimum dose not established; usual dose is 25 to 100 grams in adults and adolescents; 25 to 50 grams in children aged 1 to 12 years (or 0.5 to 1 gram/kilogram body weight) ; and 0.5 to 1 gram/kilogram in infants up to 1 year old (Chyka et al, 2005).
    1) Routine use of a cathartic with activated charcoal is NOT recommended as there is no evidence that cathartics reduce drug absorption and cathartics are known to cause adverse effects such as nausea, vomiting, abdominal cramps, electrolyte imbalances and occasionally hypotension (None Listed, 2004).
    b) ADVERSE EFFECTS/CONTRAINDICATIONS
    1) Complications: emesis, aspiration (Chyka et al, 2005). Aspiration may be complicated by acute respiratory failure, ARDS, bronchiolitis obliterans or chronic lung disease (Golej et al, 2001; Graff et al, 2002; Pollack et al, 1981; Harris & Filandrinos, 1993; Elliot et al, 1989; Rau et al, 1988; Golej et al, 2001; Graff et al, 2002). Refer to the ACTIVATED CHARCOAL/TREATMENT management for further information.
    2) Contraindications: unprotected airway (increases risk/severity of aspiration) , nonfunctioning gastrointestinal tract, uncontrolled vomiting, and ingestion of most hydrocarbons (Chyka et al, 2005).
    B) GASTRIC LAVAGE
    1) Gastric lavage may also be considered for a relatively recent or very large ingestion that has occurred within the past hour.
    2) INDICATIONS: Consider gastric lavage with a large-bore orogastric tube (ADULT: 36 to 40 French or 30 English gauge tube {external diameter 12 to 13.3 mm}; CHILD: 24 to 28 French {diameter 7.8 to 9.3 mm}) after a potentially life threatening ingestion if it can be performed soon after ingestion (generally within 60 minutes).
    a) Consider lavage more than 60 minutes after ingestion of sustained-release formulations and substances known to form bezoars or concretions.
    3) PRECAUTIONS:
    a) SEIZURE CONTROL: Is mandatory prior to gastric lavage.
    b) AIRWAY PROTECTION: Place patients in the head down left lateral decubitus position, with suction available. Patients with depressed mental status should be intubated with a cuffed endotracheal tube prior to lavage.
    4) LAVAGE FLUID:
    a) Use small aliquots of liquid. Lavage with 200 to 300 milliliters warm tap water (preferably 38 degrees Celsius) or saline per wash (in older children or adults) and 10 milliliters/kilogram body weight of normal saline in young children(Vale et al, 2004) and repeat until lavage return is clear.
    b) The volume of lavage return should approximate amount of fluid given to avoid fluid-electrolyte imbalance.
    c) CAUTION: Water should be avoided in young children because of the risk of electrolyte imbalance and water intoxication. Warm fluids avoid the risk of hypothermia in very young children and the elderly.
    5) COMPLICATIONS:
    a) Complications of gastric lavage have included: aspiration pneumonia, hypoxia, hypercapnia, mechanical injury to the throat, esophagus, or stomach, fluid and electrolyte imbalance (Vale, 1997). Combative patients may be at greater risk for complications (Caravati et al, 2001).
    b) Gastric lavage can cause significant morbidity; it should NOT be performed routinely in all poisoned patients (Vale, 1997).
    6) CONTRAINDICATIONS:
    a) Loss of airway protective reflexes or decreased level of consciousness if patient is not intubated, following ingestion of corrosive substances, hydrocarbons (high aspiration potential), patients at risk of hemorrhage or gastrointestinal perforation, or trivial or non-toxic ingestion.
    C) WHOLE BOWEL IRRIGATION
    1) Whole bowel irrigation with polyethylene glycol solution might be considered for ingestions of multiple seeds, especially if the patient presents more than an hour after ingestion, but it has not been studied.
    6.5.3) TREATMENT
    A) SUPPORT
    1) MANAGEMENT OF MILD TO MODERATE TOXICITY: Significant toxicity is not expected after ingestion of intact or whole seeds (ie, castor bean, abrus precatorius seeds). Management of mild to moderate toxicity requires only good supportive care. Treatment may include volume resuscitation for vomiting and diarrhea, and electrolyte restoration for abnormalities.
    2) MANAGEMENT OF SEVERE TOXICITY: Severe toxicity may require more aggressive treatment, including intubation and the use of pressors for hypotension. Treat seizures with benzodiazepines, add propofol or barbiturates, if seizures persist.
    B) MONITORING OF PATIENT
    1) Monitor vital signs and mental status.
    2) Monitor serum electrolytes, renal function, and liver enzymes in symptomatic patients.
    3) Laboratory radioimmunoassay is available to measure ricin levels after ingestion, however, specific ricin concentrations are neither readily available nor useful in guiding therapy.
    C) EXPERIMENTAL THERAPY
    1) Many antidotes have been investigated, but no specific treatments are available for toxalbumin exposures (Corwin, 1961). Various antibodies have been developed, but are not used clinically (Hart, 1963).
    2) Both a goat antiricin polyclonal and a mouse antiricin A-chain monoclonal antibody have been shown to neutralize ricin in castor bean extract (Wannemacher et al, 1991; Lemley & Wright, 1991).
    a) PRELIMINARY HUMAN STUDY: RECOMBINANT RICIN VACCINE (RiVax): A pilot clinical trial with 15 volunteers was conducted to determine the safety and efficacy of a recombinant ribotoxic A chain (RTA) ricin vaccine (RiVax(TM) following preclinical trials in mice and rabbits indicating that the vaccine was safe (Smallshaw et al, 2007; Smallshaw et al, 2002). Three groups of 5 volunteers were administered the vaccine intramuscularly 3 times at monthly intervals with doses of 10, 33 or 100 mcg of the vaccine. The vaccine was considered safe and produced only mild injection site symptoms in most patients. No grade 3 or 4 toxicities were reported. Ricin-neutralizing antibodies were produced in 1 of 5 subjects in the low dose-group, 4 of 5 subjects in the intermediate-dose group, and all 5 subjects in the high-dose group. The authors suggested further study and development of the vaccine (Vitetta et al, 2006).
    D) FLUID/ELECTROLYTE BALANCE REGULATION
    1) Fluid and electrolyte status may deteriorate suddenly and severely due to vomiting and diarrhea, as well as generalized capillary injury. Fluid and electrolyte status, as well as fluid loss must be corrected with appropriate fluid and electrolyte replacement.
    2) MAINTENANCE of adequate fluid volume and high urine flow rates should have a major role in preventing development of acute renal failure.
    E) HYPOGLYCEMIA
    1) Monitor for alterations (increased or decreased) in blood sugar. Use dextrose infusion for maintenance.

Inhalation Exposure

    6.7.1) DECONTAMINATION
    A) Move patient from the toxic environment to fresh air. Monitor for respiratory distress. If cough or difficulty in breathing develops, evaluate for hypoxia, respiratory tract irritation, bronchitis, or pneumonitis.
    B) OBSERVATION: Carefully observe patients with inhalation exposure for the development of any systemic signs or symptoms and administer symptomatic treatment as necessary.
    C) INITIAL TREATMENT: Administer 100% humidified supplemental oxygen, perform endotracheal intubation and provide assisted ventilation as required. Administer inhaled beta-2 adrenergic agonists, if bronchospasm develops. Consider systemic corticosteroids in patients with significant bronchospasm (National Heart,Lung,and Blood Institute, 2007). Exposed skin and eyes should be flushed with copious amounts of water.

Eye Exposure

    6.8.1) DECONTAMINATION
    A) EYE IRRIGATION, ROUTINE: Remove contact lenses and irrigate exposed eyes with copious amounts of room temperature 0.9% saline or water for at least 15 minutes. If irritation, pain, swelling, lacrimation, or photophobia persist after 15 minutes of irrigation, an ophthalmologic examination should be performed (Peate, 2007; Naradzay & Barish, 2006).

Dermal Exposure

    6.9.1) DECONTAMINATION
    A) DERMAL DECONTAMINATION
    1) DECONTAMINATION: Remove contaminated clothing and wash exposed area thoroughly with soap and water for 10 to 15 minutes. A physician may need to examine the area if irritation or pain persists (Burgess et al, 1999).

Enhanced Elimination

    A) HEMODIALYSIS
    1) Due to their large molecular size (ricin: 66 kilodaltons; abrin: 65 kilodaltons), hemodialysis is unlikely to be useful.
    B) HEMOPERFUSION
    1) Charcoal hemoperfusion may adsorb circulating toxalbumins. No clinical experience has been reported.

Abstracts

Case Reports

    A) RICIN: A 49-year-old Bulgarian defector was struck in the thigh with a bored out 1.5 mm platinum pellet while waiting for a bus near London's Waterloo bridge in September of 1978. The pellet had been drilled out with an internal volume of 0.28 cu mm. Within a few hours the patient became very sick with a high fever. On admission to St. James Hospital the next day, his fever continued, his white count reached 33,000, his condition rapidly declined with falling blood pressure and temperature; he died 3 days after the injury. Though no specific isolation of poison was obtained, authorities were satisfied that "the symptomatology and exceptionally high toxicity for such a small dose made ricin virtually the only choice" (Knight, 1979).
    B) CASTOR BEANS: A family of four chewed 2,3,8, and 10 castor beans respectively. Three developed miosis, all four developed nausea and vomiting and the two patients with the higher doses had abdominal cramping, diarrhea, and dehydration. The 12-year-old who had chewed 2 seeds, complained of vomiting and nausea for 3 days without diarrhea. The 8-year-old who chewed 10 seeds had copious diarrhea and dehydration. This patient developed microscopic hematuria and cylindruria on the 5th day for a brief time. These patients were treated with urine alkalization to avoid hemoglobin precipitation of the tubules and vigorous fluid replacement. All recovered without sequelae (Malizia et al, 1977).
    C) ABRUS PRECATORIUS: A 42-year-old man developed bloody diarrhea, abdominal pain, seizures, altered sensorium, fever, coma with depressed reflexes, and bilateral constricted pupils after eating Abrus precatorius seeds (white with black eye). A lumbar puncture revealed evidence of hemorrhage, and increased CSF protein and lymphocytes. Urinalysis showed mild proteinuria and occasional RBCs, along with a serum creatinine of 1.6 mg/dL. Following supportive therapy, he recovered without further sequelae (Pillay et al, 2005).

Range Of Toxicity

Summary

    A) SUMMARY: Minimal toxicity is expected, if the beans are swallowed intact without chewing. Ricin is considered among one of the most toxic compounds known to man. It is theorized that a single castor bean may be severely toxic and even lethal to a child. Different estimates have been made for the minimal lethal dose to adults and may be influenced by a number of variables, such as the qualities (eg, size and weight) of the castor beans ingested, as well as the patient's own comorbidities.
    B) CASTOR BEANS: These beans contain approximately 1% to 10% of ricin. Estimates for minimal lethality include 8 to 10 castor beans or 30 mg up to 1 mg/kg for an adult. However, there are case reports of children ingesting 2 or more castor beans and adults ingesting up to 30 castor beans with survival, though they did have symptoms of gastroenteritis.
    C) RICIN INJECTION: An injection of less than 3 mcg/kg of ricin is thought to be able to cause death.
    D) ABRIN: The abrin content in a single Abrus precatorius seed is approximately 0.15%. Though there is a case report of death following ingestion of a single bean, there are also reports of survival after ingestion of multiple abrin beans.

Minimum Lethal Exposure

    A) SPECIFIC SUBSTANCE
    1) RICIN
    a) ORAL
    1) Ricin is among the most toxic compounds known.
    2) A single castor bean may be severely toxic and perhaps lethal to a child.
    3) 8 to 10 beans is generally considered to be the minimum lethal dose for an adult (Balint, 1974).
    4) A dose of 1 mg/kg orally is probably close to the minimum lethal dose as the toxin is very poorly absorbed (Kopferschmitt et al, 1983). It has been estimated that 30 mg of ricin orally in an adult would be potentially lethal (Kaszas & Papp, 1960).
    5) Ricin doses estimated from the number of castor beans ingested may not be accurate due to a number of variabilities including size, weight, and moisture content of the beans, the region, season, and period of plant growth at the time of harvesting the beans, and the degree of mastication, age, and comorbidities of the patient who ingested the beans (Audi et al, 2005).
    b) INJECTED
    1) HUMAN: The human death due to a ricin laden projectile probably represented less than 3 mcg/kg (Knight, 1979).
    2) ANIMAL DATA: The mouse mean lethal dose is 1 nanogram ricin nitrogen intraperitoneally/gram body weight (1 mcg/kg) with death occurring after 48 hours (Budavari, 1989).
    c) RICIN CONTENT OF CASTOR BEANS
    1) Castor beans generally contain about 1% to 10% ricin (Waller & Negi, 1958; Balint, 1974). Balint (1974) has calculated that 1 kg of ricin would be lethal to 3.6 million people as compared to an equal amount of cyanide being lethal only to 116,000 (Balint, 1974).
    2) ABRIN
    a) ORAL
    1) Death followed ingestion of a single Abrus precatorius that had been chewed (Hart, 1963).
    2) Sublethal toxicity has occurred with one-half to 2 chewed beans (Hart, 1963).
    b) ABRIN CONTENT IN ABRUS PRECATORIUS
    1) Estimated to be 0.15% (Lin et al, 1971).
    3) ABRUS PRECATORIUS
    a) A 30-year-old woman developed bloody diarrhea, epigastric pain, vomiting, and deep coma (a Glasgow Coma Score of 5 [E1M3V1]) 7 to 8 hours after ingesting 3 to 4 seeds of a plant called "ratti" (jequirity pea - Abrus precatorius). The examination of the right eye showed pupillary dilatation with downwards deviations, suggestive of third nerve palsy. She also experienced two episodes of generalized seizures in the hospital. Laboratory results revealed hepatic and renal toxicity. MRI brain scan showed altered signal intensity in bilateral peritrigonal, parieto-occipital white matter, external and internal capsules, and lentiform nuclei, suggestive of demyelination. She was diagnosed with acute demyelinating encephalitis. Her condition deteriorated further and she died 3 days later (Sahni et al, 2007).

Maximum Tolerated Exposure

    A) CASE REPORTS
    1) RICIN (ORAL)
    a) As many as 30 castor beans have been taken orally (some had been chewed) by an adult with survival. Ricin was measured by radioimmunoassay and demonstrated that very little had been absorbed (Kopferschmitt et al, 1983).
    b) Twelve chewed castor beans were ingested by a 21-year-old man with eventual recovery; self-induced vomiting began in this case one-half hour after ingestion (Wedin et al, 1986).
    c) A child ingested 2 or more castor beans, and 2 adults ingested 4 castor beans each; they developed severe gastroenteritis, but no sequelae (Challoner & McCarron, 1990).
    2) ABRUS PRECATORIUS
    a) A 42-year-old man developed bloody diarrhea, abdominal pain, seizures, altered sensorium, fever, coma with depressed reflexes, respiratory failure, and bilateral constricted pupils after eating Abrus precatorius seeds (white with black eye). Following supportive therapy, he recovered without further sequelae (Pillay et al, 2005).
    B) CASE SERIES
    1) CASTOR BEAN SEED
    a) A retrospective, observational review was conducted by the California Poison Control Centers from 2001 to 2011 to determine the characteristics of castor bean seed (Ricinus communis) exposure, serious morbidity and mortality were not reported and there were no reports of delayed symptoms. Gastrointestinal symptoms were the most common (59 cases (67%) clinical finding. Ingesting 10 or more seeds was likely to result in gastrointestinal symptoms compared to those ingesting 10 or less seeds (odds ratio 7.5 (95% Confidence Interval). In one case, nausea and diarrhea occurred after ingesting 6 ground castor bean seeds with complete recovery in 24 hours. Another patient ingested 10 chewed castor bean seeds and developed gastrointestinal symptoms (ie, nausea, vomiting, diarrhea, and abdomina pain) and recovered after 8 days; laboratory studies remained normal. Hematochezia and vomiting occurred in a patient that intentionally ingested and injected castor bean seed extract requiring hospital admission for 2 days with complete recovery. Of the 22 (26%) cases, requiring hospital admission the median length of stay was 2 days (range, 1 to 10 days) and the median number of seeds ingested was 8.5 seeds (range, 1 to 20 seeds). In most cases, patient's admitted to chewing the seeds. However, symptoms were self-limited in all cases (Thornton et al, 2014).

Serum Plasma Blood Concentrations

    7.5.2) TOXIC CONCENTRATIONS
    A) TOXIC CONCENTRATION LEVELS
    1) GENERAL
    a) Toxalbumins are not typically measured.
    b) RICIN LEVELS - In one case, radioimmunoassay following an oral ingestion of 30 beans by an adult resulted in a plasma ricin level of 1.5 micrograms/liter and a urine level of 0.3 micrograms/liter. The 24 hour excretion of ricin was 0.72 microgram per day. This investigator found only 0.35 milligram of ricin in 0.9 gram seeds (Kopferschmitt et al, 1983).

Toxicity Information

    7.7.1) TOXICITY VALUES
    A) LD50- (INHALATION)MOUSE:
    1) 3 to 5 mcg/kg (ricin particles less than 5 micrometers in size) (Audi et al, 2005)
    B) LD50- (INTRAPERITONEAL)MOUSE:
    1) 70 ng/25 g (Olsnes & Pihl, 1973)
    C) LD50- (ORAL)MOUSE:
    1) 30 mg/kg (Audi et al, 2005)
    D) LD50- (SUBCUTANEOUS)MOUSE:
    1) 0.2 mg/kg (Niyogi, 1969)

Pharmacology Toxicology

Pharmacologic Mechanism

    A) The toxalbumins, diphtheria toxin, botulinus toxin, and probably many other potent toxins share a unique two-step pharmacology (Olsnes et al, 1974).
    B) RICIN -
    1) Ricin has a molecular weight of 66,000.
    2) It consists of two approximately equal size subunits (A and B) bound by disulfide linkage. When the link is broken, the toxicity to intact cells is essentially nullified. The B part of the toxin binds to galactose containing receptors in the cell wall, and the intact two part toxin is actively transported into the cell (Olsnes et al, 1974).
    3) Thereafter, the A part or effector subunit inhibits protein synthesis, probably by disabling the 60S ribosomal subunits (Gessner & Irvin, 1980). This process must be enzymatically multiplied since less than 10 molecules of ricin can kill a HELA cell in culture and there are about 500,000 ribosomes per cell.
    C) CANCER RESEARCH -
    1) The extreme toxicity of the A part has placed this compound clearly in the center of the development of immunotoxicologic agents for cancer chemotherapy. Such agents combine the tumor selectivity of an antibody to the specific antigenic marker on the tumor with an extremely potent poison such as the ricin B unit (Howell & Villemez, 1984).
    2) These agents seem to hold considerable promise as anti-cancer or anti-cancer chemotherapy and ricin is thus far the most widely applied toxin (Onozaki et al, 1972; Lin et al, 1970; Casellas et al, 1985).

Toxicologic Mechanism

    A) PROTEIN SYNTHESIS INHIBITION - Although the principal toxicity of the toxalbumins appear to be protein synthesis inhibition (Greco et al, 1974; Spyker et al, 1982), other toxicologic mechanisms of action may occur including apoptosis pathways, direct cell membrane damage, alteration of membrane structure and function, and release of cytokine inflammatory mediators (Audi et al, 2005). Clinical effects include:
    1) An initial aggregation/sludge formation of red cells within the first hour
    2) Adrenal insufficiency
    3) Hepatic and adrenal failure
    4) Endothelial damage
    5) In severe cases, diffuse and profound capillary hemorrhage occurs
    B) AMINO ACIDS - Abrin does not inhibit mitochondrial respiration in vitro, but does interfere with amino acid incorporation in the liver (study done on rats)(Lin et al, 1971).

Physicochemical

Physical Characteristics

    A) The amino acid composition has been studied for ricin which is found to contain 20% glutamic acid, 15% leucine, 11.7% arginine, 6% lysine, and smaller amounts of the other amino acids.

Molecular Weight

    A) ABRIN: A chain--30,000; B chain-- 35,000; Total-- 65,000 (Olsnes et al, 1974)
    B) RICIN: A chain-- 32,000; B chain-- 34,000; Total-- 66,000 (Olsnes et al, 1974)

Animal Toxicology

Clinical Effects

    11.1.1) AVIAN/BIRD
    A) CHICKENS - In hens, Ricinus toxicity is seen as moulting, emaciation, and cessation of laying. Chicks poisoned with 5% in their diet, developed impaired vision, growth depression, locomotor difficulties, anemia, and enterohepatonephropathies (El Badwi et al, 1992).
    11.1.2) BOVINE/CATTLE
    A) Exposure to contaminated cattle cake led to severe diarrhea with blood clots in the stool. There were two abortions, and milk flow was severely reduced (Fox, 1961).
    B) In another exposure, 9 of 25 newborn calves died after being fed 1 kg of castor bean cake daily. They developed swollen joints, watery diarrhea, weak pulse, shortness of breath, and severe weakness (Mel'nik & Koltun, 1973).
    C) Eleven cattle fed castor bean husks died or were killed because they were too weak to stand, had a fast, weak pulse, had subnormal temperatures, and were passing feces containing blood and mucus. The lethal dose in this case was estimated at being about 250 grams of husks (Anderson, 1948).
    11.1.3) CANINE/DOG
    A) Several dogs died of circulatory failure after experiencing severe gastroenteritis with hemorrhage. They had eaten a "fertilizer" that contained 25 percent castor beans (Krieger-Huber, 1980).
    11.1.4) CAPRINE/GOAT
    A) Profuse diarrhea and abdominal pain were seen in a goat who died from eating castor beans. The beans were found in its stomach (Anon, 1982).
    11.1.5) EQUINE/HORSE
    A) Poisoned horses develop symptoms similar to cattle. Early symptoms could be confused with a respiratory infection (Cooper & Johnson, 1984; Lapcevic et al, 1960).
    B) Forty eight horses were poisoned when castor beans were accidentally mixed with grain during shipping (McCunn et al, 1945). Signs included tachycardia, sweating, fever, rocking gait, muscle spasms, and abdominal pain.
    11.1.10) PORCINE/SWINE
    A) Severe vomiting and diarrhea, weakness, incoordination, and a seizure were seen in pigs fed a meal containing 0.3 to 1.4 grams of castor seed husk per 100 grams of feed. Recovery was not complete, even three months later (Geary, 1950).

Range Of Toxicity

    11.3.2) MINIMAL TOXIC DOSE
    A) GENERAL
    1) Estimated Lethal Dose (Cooper & Johnson, 1984)
    1) Cattle: 1 to 2 g/kg
    2) Fowl: 1 to 2 g/kg
    3) Goat: 5.5 g/kg
    4) Horse: 0.1 g/kg
    5) Pig: 1 to 2 g/kg
    6) Rabbit: 1 to 2 g/kg
    7) Sheep: 1 to 2 g/kg

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