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PLANTS-HOLLY

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Classification   |    Detailed evidence-based information

Substances Included Synonyms

Therapeutic Toxic Class

    A) Holly is the common name for a number of different species of the Ilex genus. Many are commonly used as garden plants and Christmas decorations.
    1) Ingestion of the berries is not uncommon (Anon, 1977; Veltri & Litovitz, 1984), but in one US study, 21 of 1051 (2%) plant ingestion calls involved holly (O'Leary, 1964).

Specific Substances

    A) ILEX AQUIFOLIUM (L)
    1) Christmas Holly
    2) Crocodile Holly
    3) English Holly
    4) European Holly
    5) Oregon Holly
    6) Prick Holly
    7) Sparked Holly
    ILEX ASPERLLA (Hook. & Arn) Champ. ex Benth.
    1) ILEX ASPERLLA (Hook. & Arn) Champ. ex Benth.
    ILEX CASSENE L.
    1) Mockingbird Bush
    2) Yopon
    ILEX CHINESIS
    1) Oriental Holly
    ILEX CORNUTA
    1) Chinese Holly
    ILEX GLABRA (L.) A. Gray
    1) ILEX GLABRA (L.) A. Gray
    ILEX OPACA (Ait.)
    1) American Holly
    ILEX PARAGUARIENSIS St. Hill
    1) Mate'
    2) Paraguay Tea
    3) Yerba Mate'
    ILEX PUBESCENS Hook et Arn.
    1) Maodongqing
    2) MDQ
    ILEX ROTUNDA
    1) ILEX ROTUNDA
    ILEX VERTICILLATA (L.) A. Gray
    1) ILEX VERTICILLATA (L.) A. Gray
    ILEX VOMITORIA (Ait.)
    1) Appalachian Tea
    2) Black Drink
    3) Carolina Tea
    4) Cassena
    5) Deer Holly
    6) Emetic Holly
    7) Evergreen Cassena
    8) Indian Black Drink
    9) Yaupon

Available Forms Sources

    A) SOURCES
    1) Ilex aquifolium leaves are known to contain traces of theobromine (Bohnic, 1959) and a saponin with hemolytic activity (Balansard & Flandrin, 1951).
    2) The fruits are thought to contain triterpene compounds (Budzikiewicz & Thomas, 1980; Thomas & Budzikiewicz, 1980a), and a bis-nor-monoterpene (30 mg in 20 grams of fruit) (Thomas & Budzikicwicz, 1980; (Cooper & Johnson, 1984).
    3) Older texts describe the constituents of I. aquifolium as being tannic acid, the bitter glycoside ilicin, ilexanthin, and ilicic acid but the relationship to the saponins, the triterpenes, and to the overall toxicity is unknown (Fournier, 1948; Alikaridis, 1987).
    4) A cyanogenc glycoside has also been discovered in various Ilex species (Willems, 1989).
    5) Ilex paraguayensis leaves contain 0.13% caffeine and saponins (Gosmann & Schenkel, 1989; Waud, 1932).
    B) USES
    1) Various species are used in folk medicine intended as antipyretics, teas, CNS stimulants, diuretics, and treatments for the common cold, tonsillitis, arthritis, and intestinal ulcers. Accidental ingestion of one of these herbal products may occur (Chen & Wen, 1990; Gosmann & Schenkel, 1989).
    2) Ilex asprella leaves contain a number of cytotoxic antineoplastic agents which are being tested against melanoma cell lines (Kashiwada et al, 1993). Specific toxicity from ingestion of raw leaves has not been mentioned.
    3) In China, Maodongqing ((MDQ) Ilex pubescens Hook et Arn) is an evergreen bush, in which an active extract has been obtained from the roots of this species. It is used to "improve circulation". In both experimental animals and humans it has been shown to lower blood pressure. MDQ is listed in the Chinese Pharmacopoeia of Herbal Medicine and is used clinically as a cardiovascular drug (includes treatment for angina, myocardial infarction, cerebral thrombosis, thrombophlebitis) and is available in a tablet form and an aqueous solution for intramuscular injection (Yang & Pang, 1986).
    a) In one study, experimental animals were given MDQ intravenously and developed hypotension which the authors suggested was probably due to histamine release (Yang & Pang, 1986).

Overview

Life Support

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

Clinical Effects

    0.2.1) SUMMARY OF EXPOSURE
    A) DESCRIPTION: Holly is from the Ilex species and the family Aquifoliaceae. Two commonly distributed forms of holly in the United States are English holly (Ilex aquifolium) and American holly (Ilex opaca).
    B) BACKGROUND: Although older literature cites cases ending in death, recent poison center experience would indicate gastrointestinal effects are much more common, with serious symptoms being reserved for ingestion of large numbers of berries.
    C) USES: Various species are used in folk medicine intended as antipyretics, teas, CNS stimulants, diuretics, and treatments for the common cold, tonsillitis, arthritis, and intestinal ulcers.
    D) TOXICOKINETICS: The berries contain the toxin saponin. Saponins can cause hemolysis in erythrocytes and alterations in permeability of small intestinal mucosal cells. It is suspected that saponins are partially responsible for the gastrointestinal effects observed. The toxin is found in some species of Ilex, but absorption through intact mucosa is minimal. Large ingestions may result in gastrointestinal symptoms.
    E) EPIDEMIOLOGY: Exposure can occur.
    F) WITH POISONING/EXPOSURE
    1) ADVERSE EFFECTS: Most ingestions result in minimal toxicity. Ingestion of a couple of berries most commonly results in mild to moderate gastritis and possible mild CNS depression.
    2) COMMON: Gastrointestinal symptoms are likely including nausea, vomiting, abdominal pain, and possibly diarrhea. Mild CNS depression is possible. Spiny leaves can cause mechanical damage.
    3) SERIOUS: Ingestion of a large quantity of berries may cause vomiting, diarrhea, dehydration, stupor and electrolyte imbalance. Allergic sensitization can occur. Worsening dermatitis may develop with repeat exposures.
    4) RARE: In rare cases, mydriasis, hyperthermia and drowsiness have developed.
    5) ADULTERANTS: Ilex teas have been adulterated with anticholinergic agents that have produced symptoms.
    0.2.3) VITAL SIGNS
    A) WITH POISONING/EXPOSURE
    1) Hyperthermia is an uncommon clinical effect of holly (Ilex aquifolium and Ilex opaca) exposure (Evens & Stellpflug, 2012).
    0.2.5) CARDIOVASCULAR
    A) Animal experiments have shown a digitalis-like effect, but this has not been seen in human poisonings. An herbal holly product, Maodongqing (Ilex pubescens), can cause hypotension following injection.
    0.2.7) NEUROLOGIC
    A) Various degrees of CNS depression may be expected with significant exposures to American and European hollies, but stimulation may be seen after ingestion of Mate', due to xanthine content.
    0.2.8) GASTROINTESTINAL
    A) Nausea, vomiting, diarrhea, and abdominal pain are common symptoms reported after ingestion.
    0.2.14) DERMATOLOGIC
    A) WITH POISONING/EXPOSURE
    1) The spiny leaves may cause mechanical irritation, but are considered nontoxic.
    0.2.20) REPRODUCTIVE
    A) At the time of this review, no data were available to assess the potential effects of exposure to this agent during pregnancy or lactation.
    0.2.21) CARCINOGENICITY
    A) Heavy use of some herbal Ilex products have been associated with an increase risk of cancer.

Laboratory Monitoring

    A) No specific lab work (CBC, electrolytes, urinalysis) is needed unless otherwise clinically indicated.
    B) Monitor fluids and electrolyte balance following significant vomiting and/or diarrhea.

Treatment Overview

    0.4.2) ORAL/PARENTERAL EXPOSURE
    A) MILD TO MODERATE TOXICITY
    1) Treatment is symptomatic and supportive. A few berries may produce nausea. Monitor fluid and electrolytes as necessary. Administer IV fluids to replace significant gastrointestinal loss.
    B) MANAGEMENT OF SEVERE TOXICITY
    1) Treatment is symptomatic and supportive. Severe toxicity is not anticipated. In significant exposures, the central nervous system should be monitored.
    C) DECONTAMINATION
    1) PREHOSPITAL: Gastrointestinal decontamination is unlikely to be necessary following a minor exposure (ie, ingestion of a few berries). Activated charcoal may not be indicated in patients that are already vomiting.
    2) HOSPITAL: Activated charcoal may be indicated when multiple berries have been ingested to minimize protracted emesis or diarrhea, if the patient is alert and the ingestion is recent. The airway may need to be protected before administration.
    D) PATIENT DISPOSITION
    1) HOME CRITERIA: A patient with an inadvertent minor exposure, that remains asymptomatic can be managed at home.
    2) OBSERVATION CRITERIA: Patients with a deliberate overdose, and those who are symptomatic, need to be monitored for several hours to assess fluid and electrolyte balance. Patients that remain asymptomatic can be discharged.
    3) ADMISSION CRITERIA: Patients should be admitted for severe vomiting, profuse diarrhea, severe abdominal pain, dehydration, electrolyte abnormalities and if persistent alterations in CNS function are present.
    4) CONSULT CRITERIA: Consult a poison center or medical toxicologist for assistance in managing patients with severe toxicity or in whom the diagnosis is not clear.

Range Of Toxicity

    A) TOXICITY: A minimum lethal human exposure is unknown. Ingestion of several berries may produce gastrointestinal symptoms. It is suggested that 20 to 30 berries is a toxic dose, although this has not been well documented.

Clinical Effects

Summary Of Exposure

    A) DESCRIPTION: Holly is from the Ilex species and the family Aquifoliaceae. Two commonly distributed forms of holly in the United States are English holly (Ilex aquifolium) and American holly (Ilex opaca).
    B) BACKGROUND: Although older literature cites cases ending in death, recent poison center experience would indicate gastrointestinal effects are much more common, with serious symptoms being reserved for ingestion of large numbers of berries.
    C) USES: Various species are used in folk medicine intended as antipyretics, teas, CNS stimulants, diuretics, and treatments for the common cold, tonsillitis, arthritis, and intestinal ulcers.
    D) TOXICOKINETICS: The berries contain the toxin saponin. Saponins can cause hemolysis in erythrocytes and alterations in permeability of small intestinal mucosal cells. It is suspected that saponins are partially responsible for the gastrointestinal effects observed. The toxin is found in some species of Ilex, but absorption through intact mucosa is minimal. Large ingestions may result in gastrointestinal symptoms.
    E) EPIDEMIOLOGY: Exposure can occur.
    F) WITH POISONING/EXPOSURE
    1) ADVERSE EFFECTS: Most ingestions result in minimal toxicity. Ingestion of a couple of berries most commonly results in mild to moderate gastritis and possible mild CNS depression.
    2) COMMON: Gastrointestinal symptoms are likely including nausea, vomiting, abdominal pain, and possibly diarrhea. Mild CNS depression is possible. Spiny leaves can cause mechanical damage.
    3) SERIOUS: Ingestion of a large quantity of berries may cause vomiting, diarrhea, dehydration, stupor and electrolyte imbalance. Allergic sensitization can occur. Worsening dermatitis may develop with repeat exposures.
    4) RARE: In rare cases, mydriasis, hyperthermia and drowsiness have developed.
    5) ADULTERANTS: Ilex teas have been adulterated with anticholinergic agents that have produced symptoms.

Vital Signs

    3.3.1) SUMMARY
    A) WITH POISONING/EXPOSURE
    1) Hyperthermia is an uncommon clinical effect of holly (Ilex aquifolium and Ilex opaca) exposure (Evens & Stellpflug, 2012).

Heent

    3.4.3) EYES
    A) WITH POISONING/EXPOSURE
    1) Mydriasis is an uncommon clinical effect of holly (Ilex aquifolium and Ilex opaca) exposure (Evens & Stellpflug, 2012).

Cardiovascular

    3.5.1) SUMMARY
    A) Animal experiments have shown a digitalis-like effect, but this has not been seen in human poisonings. An herbal holly product, Maodongqing (Ilex pubescens), can cause hypotension following injection.
    3.5.2) CLINICAL EFFECTS
    A) HYPOTENSIVE EPISODE
    1) WITH THERAPEUTIC USE
    a) HERBAL PRODUCT: A Chinese herbal holly product, Maodongqing, is used for the treatment of cardiovascular diseases (i.e., angina pectoris, hypertension, myocardial infarction, cerebral thrombosis, and thrombophlebitis). Injection of this product causes hypotension, ingestion may also produce hypotension, but this has not been tested clinically. Maodongqing is the common name for Ilex pubescens. In animal studies, the authors found that the hypotensive effects were probably due to histamine release (Yang & Pang, 1986).
    B) LACK OF EFFECT
    1) Cardiac effects were not reported after ingestions of berries (Rodriques et al, 1984).
    3.5.3) ANIMAL EFFECTS
    A) ANIMAL STUDIES
    1) HEART DISORDER
    a) Cardiotonic activity similar to that of digitalis was reported from extracts of the fruits and seeds of Ilex opaca and Ilex aquifolium. These experiments were done on frog and rabbit hearts (Waud, 1931) (Waud, 1932) (Waud, 1932a).

Respiratory

    3.6.2) CLINICAL EFFECTS
    A) DYSPNEA
    1) WITH POISONING/EXPOSURE
    a) Dyspnea is an uncommon clinical effect of holly (Ilex aquifolium and Ilex opaca) exposure (Evens & Stellpflug, 2012).

Neurologic

    3.7.1) SUMMARY
    A) Various degrees of CNS depression may be expected with significant exposures to American and European hollies, but stimulation may be seen after ingestion of Mate', due to xanthine content.
    3.7.2) CLINICAL EFFECTS
    A) ALTERED MENTAL STATUS
    1) WITH POISONING/EXPOSURE
    a) Various degrees of CNS depression have been reported after ingestion of American and European hollies (Arena, 1979).
    b) Altered mental status is an uncommon clinical effect of holly (Ilex aquifolium and Ilex opaca) exposure (Evens & Stellpflug, 2012).
    B) DROWSINESS
    1) WITH POISONING/EXPOSURE
    a) Drowsiness is an uncommon clinical effect of holly (Ilex aquifolium and Ilex opaca) exposure (Evens & Stellpflug, 2012).
    b) CASE SERIES: Two children ingested a "handful" of berries; one of the children became drowsy after vomiting several times (over 90 minutes). The child had been given ipecac prior to the drowsiness (Rodriques et al, 1984).
    C) ATAXIA
    1) WITH POISONING/EXPOSURE
    a) Ataxia is an uncommon clinical effect of holly (Ilex aquifolium and Ilex opaca) exposure (Evens & Stellpflug, 2012).

Gastrointestinal

    3.8.1) SUMMARY
    A) Nausea, vomiting, diarrhea, and abdominal pain are common symptoms reported after ingestion.
    3.8.2) CLINICAL EFFECTS
    A) NAUSEA AND VOMITING
    1) WITH POISONING/EXPOSURE
    a) Gastrointestinal complaints such as nausea, abdominal pain, diarrhea, and vomiting are the most common effects seen after ingestion of berries. As few as two berries may initiate symptoms such as nausea (Frohne & Pfander, 1983; Schilling & Speaker, 1980; Rodriques et al, 1984; Lampe & McCann, 1985).
    b) Vomiting continued intermittently for up to 20 hours in one case administered ipecac (Rodriques et al, 1984). The prolonged symptoms may have been contributed by the use of ipecac.
    B) DIARRHEA
    1) WITH POISONING/EXPOSURE
    a) Diarrhea is another frequent symptom reported after berry ingestion (Frohne & Pfander, 1983). It may occur up to 20 hours postingestion (Rodriques et al, 1984).
    b) Saponins generally cause the diarrhea and gastrointestinal upset that can occur following ingestion (DerMarderosian, 1996).

Hematologic

    3.13.2) CLINICAL EFFECTS
    A) HEMOLYSIS
    1) WITH POISONING/EXPOSURE
    a) Balansard & Flandrin (1951) isolated a saponin (heteroside) from the leaves that had hemolytic activity. Leaves are usually not ingested in human poisonings, and hemolysis is not a common finding after ingestion.

Dermatologic

    3.14.1) SUMMARY
    A) WITH POISONING/EXPOSURE
    1) The spiny leaves may cause mechanical irritation, but are considered nontoxic.
    3.14.2) CLINICAL EFFECTS
    A) SKIN IRRITATION
    1) WITH POISONING/EXPOSURE
    a) The thorny leaves of the holly may cause mechanical irritation, the leaves of most species are generally considered to be nontoxic (Evens & Stellpflug, 2012; DerMarderosian, 1996; Mitchell & Rook, 1979).
    B) ALLERGIC SENSITIZATION
    1) WITH POISONING/EXPOSURE
    a) Following repeat exposures to holly, allergic sensitization and worsening dermatitis can develop (Evens & Stellpflug, 2012).
    C) DERMATITIS
    1) WITH POISONING/EXPOSURE
    a) Dermatitis may occasionally develop following exposure (Evens & Stellpflug, 2012).

Musculoskeletal

    3.15.2) CLINICAL EFFECTS
    A) MUSCLE WEAKNESS
    1) WITH POISONING/EXPOSURE
    a) Muscle weakness is an uncommon clinical effect of holly (Ilex aquifolium and Ilex opaca) exposure (Evens & Stellpflug, 2012).

Reproductive

    3.20.1) SUMMARY
    A) At the time of this review, no data were available to assess the potential effects of exposure to this agent during pregnancy or lactation.
    3.20.2) TERATOGENICITY
    A) LACK OF INFORMATION
    1) At the time of this review, no data were available to assess the teratogenic potential of this agent.
    3.20.3) EFFECTS IN PREGNANCY
    A) LACK OF INFORMATION
    1) At the time of this review, no data were available to assess the potential effects of exposure to this agent during pregnancy or lactation.

Carcinogenicity

    3.21.2) SUMMARY/HUMAN
    A) Heavy use of some herbal Ilex products have been associated with an increase risk of cancer.
    3.21.3) HUMAN STUDIES
    A) ILEX PARAGUARIENSIS (MATE')-
    1) A case control study of 111 incident cases of bladder cancer and 222 controls found a 7 fold increase in risk for men who were heavy consumers of mate' tea. A similar result was found for women. Cases were adjusted for age, residence, social class, hospital of treatment, type of tobacco, smoking intensity, smoking duration, and vegetable consumption (DeStefani et al, 1991).

Laboratory Monitoring

Monitoring Parameters Levels

    4.1.1) SUMMARY
    A) No specific lab work (CBC, electrolytes, urinalysis) is needed unless otherwise clinically indicated.
    B) Monitor fluids and electrolyte balance following significant vomiting and/or diarrhea.

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) Patients should be admitted for severe vomiting, profuse diarrhea, severe abdominal pain, dehydration, electrolyte abnormalities and if persistent alterations in CNS function are present.
    6.3.1.2) HOME CRITERIA/ORAL
    A) A patient with an inadvertent minor exposure, that remains asymptomatic can be managed at home.
    6.3.1.3) CONSULT CRITERIA/ORAL
    A) Consult a poison center or medical toxicologist for assistance in managing patients with severe toxicity or in whom the diagnosis is not clear.
    6.3.1.5) OBSERVATION CRITERIA/ORAL
    A) Patients with a deliberate overdose, and those who are symptomatic, need to be monitored for several hours to assess fluid and electrolyte balance. Patients that remain asymptomatic can be discharged.

Monitoring

    A) No specific lab work (CBC, electrolytes, urinalysis) is needed unless otherwise clinically indicated.
    B) Monitor fluids and electrolyte balance following significant vomiting and/or diarrhea.

Oral Exposure

    6.5.1) PREVENTION OF ABSORPTION/PREHOSPITAL
    A) SUMMARY
    1) Gastrointestinal decontamination is unlikely to be necessary following a minor exposure (ie, ingestion of a few berries).
    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) 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.
    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).
    6.5.3) TREATMENT
    A) SUPPORT
    1) MANAGEMENT OF MILD TO MODERATE TOXICITY
    a) Treatment is symptomatic and supportive with special attention to replacement of fluids and electrolytes lost during vomiting and/or diarrhea (Lampe & McCann, 1985).
    2) MANAGEMENT OF SEVERE TOXICITY
    a) Treatment is symptomatic and supportive. Severe toxicity is not anticipated. In significant exposures, the central nervous system should be monitored.
    B) MONITORING OF PATIENT
    1) No specific lab work (CBC, electrolytes, urinalysis) is needed unless otherwise clinically indicated.
    2) Monitor fluids and electrolytes as indicated.

Enhanced Elimination

    A) SUMMARY
    1) No studies have addressed the utilization of extracorporeal elimination techniques in poisoning with this agent.

Abstracts

Case Reports

    A) CONTAMINATION
    1) Ilex paraguariensis (mate' tea) was reported to produce a number of cases of anticholinergic poisoning (e.g., agitation, incoherency, flushed and dry skin, tachycardia, dilated pupils). Mate' does not contain appreciable amounts of anticholinergic substances, but this particular tea was contaminated with atropine, scopolamine, and hyoscyamine (MMWR, 1995; DeAnnuntis et al, 1994).
    B) PEDIATRIC
    1) Rodriques et al (1984) reported 2-year-old twins who ate an unknown amount ("handful") of berries from the Ilex opaca species. The children were given 15 mL of ipecac and vomited within 50 minutes (Rodriques et al, 1984):
    a) The first twin, who appeared from the vomitus to have eaten more berries, vomited ten more times over the next 40 minutes and became drowsy. Because of further vomiting she was sent to her physician where she vomited small volumes of fluid about 40 times over the next 6 hours. She experienced an episode of green, watery, diarrhea, and vomited 3 more times during the next day.
    b) The second child vomited 5 times during the first 6 hours and passed a semi-solid stool at about 20 hours after ingestion. She did not become drowsy.
    c) Both children were without symptoms 20 hours after ingestion. The ipecac may have contributed to the drowsiness observed.

Range Of Toxicity

Summary

    A) TOXICITY: A minimum lethal human exposure is unknown. Ingestion of several berries may produce gastrointestinal symptoms. It is suggested that 20 to 30 berries is a toxic dose, although this has not been well documented.

Minimum Lethal Exposure

    A) SUMMARY
    1) A minimum lethal human exposure is unknown.
    2) Although 20 to 30 berries are often referred to as the "lethal dose" (Muenscher, 1957; DerMarderosian, 1996); however, no specific reference or cases could be found to document this number.

Maximum Tolerated Exposure

    A) SUMMARY
    1) As few as two berries may elicit gastrointestinal symptoms such as nausea (Frohne & Pfander, 1983).
    2) One study recorded 9 cases of slight symptoms from 64 exposure calls (Krienke & von Muhlendahl, 1980).

Pharmacology Toxicology

Toxicologic Mechanism

    A) The gastrointestinal effects are thought to be due to saponins (West et al, 1977; DerMarderosian, 1996), but the discovery of cyanogenic glucosides may confuse the picture. No specific toxin has been determined as the primary cause of the symptoms.

References

General Bibliography

    1) Alaspaa AO, Kuisma MJ, Hoppu K, et al: Out-of-hospital administration of activated charcoal by emergency medical services. Ann Emerg Med 2005; 45:207-12.
    2) Alikaridis F: Natural constituents of Ilex species. J Ethnopharmacol 1987; 20:121-144.
    3) Anon: Bulletin, National Clearinghouse for Poison Control Centers, US Food & Drug Administration, Rockville, MD, 1977.
    4) Arena JM: Are holly berries toxic? (Letter). JAMA 1979; 242:2341.
    5) Balansard J & Flandrin P: Heterosides of the leaves of the holly tree (Ilex aquifolium). Chem Abstr 1951; 45:7307.
    6) Bohnic P: Contribution to the knowledge of the chemistry of holly (Ilex aquifolium). Farm Vestn (Ljubljana) 1959; 10:57-58.
    7) Budzikiewicz H & Thomas H: p-Cumaroxy-ursolsaure, ein neur Inhaltstoff von Ilex aquifolium L. Z Naturforsch 1980; 35b:230-231.
    8) Chen ZL & Wen D-X: Ilexrotunin: a dimeric sinapaldehyde glucoside from Ilex rotunda. Planta Med 1990; 56:573.
    9) Chyka PA, Seger D, Krenzelok EP, et al: Position paper: Single-dose activated charcoal. Clin Toxicol (Phila) 2005; 43(2):61-87.
    10) Cooper MR & Johnson AW: Poisonous Plants in Britain. Ministry of Agriculture Fisheries and Food. Ref Book 161, Her Majesty's Stationery Office, Norwich, UK, 1984.
    11) Dagnone D, Matsui D, & Rieder MJ: Assessment of the palatability of vehicles for activated charcoal in pediatric volunteers. Pediatr Emerg Care 2002; 18:19-21.
    12) DeAnnuntis GJ, Fill S, & Meggs WJ: Anticholinergic poisoning from paraguay tea: A need for further regulation. Vet Hum Toxicol 1994; 36(4):359.
    13) DeStefani E, Correa P, & Fierro L: Black tobacco, mate', and bladder cancer. A case-controlled study from Uruguay. Cancer 1991; 67(2):536-540.
    14) DerMarderosian A: Topic: Holly - The Review of Natural Products, Facts and Comparisons, St. Louis, MO, 1996.
    15) Elliot CG, Colby TV, & Kelly TM: Charcoal lung. Bronchiolitis obliterans after aspiration of activated charcoal. Chest 1989; 96:672-674.
    16) Evens ZN & Stellpflug SJ : Holiday plants with toxic misconceptions. West J Emerg Med 2012; 13(6):538-542.
    17) FDA: Poison treatment drug product for over-the-counter human use; tentative final monograph. FDA: Fed Register 1985; 50:2244-2262.
    18) Fournier P: Plants Medicinales et Veneneuses de France, P LeChavalier, Paris, France, 1948.
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