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PLANTS-CHINABERRY

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Classification   |    Detailed evidence-based information

Substances Included Synonyms

Therapeutic Toxic Class

    A) Melia azedarach, also known commonly as Chinaberry, is a tree that grows in Asia, Australia, Hawaii, Africa, South America, and parts of the southern United States. It should not be confused with the Neem oil tree (Azadirachta indica formerly known as Melia azadirachta). The fruit and bark are considered poisonous. Some genetic variations may exist producing variations in toxin content. The ripe fruit may be more toxic than the unripe fruit which is more toxic than other parts.
    B) NOTE: The common names applied to this plant are also used to refer to a number of other plants of different genus and species. This plant should NOT be confused with the common lilac, cedar, or umbrella tree of commerce.

Specific Substances

    A) COMMON NAMES
    1) African Lilac Tree
    2) Bead Tree
    3) Chinaberry
    4) China berry tree
    5) China Tree
    6) False Sycamore
    7) Hog Bush
    8) Indian Lilac
    9) Japanese Bead Tree
    10) Inia
    11) Paradise Tree
    12) Persian Lilac
    13) Pride of China
    14) Pride of India
    15) Syrian Bead Tree
    16) Texas Umbrella Tree
    17) West Indian Lilac
    18) Reference: (Nelson et al, 2007)
    BOTANICAL NAME
    1) Melia azedarach
    2) Family: Meliaceae
    3) Reference: (Nelson et al, 2007)

Available Forms Sources

    A) USES
    1) The plant has been used as an herbal medication. The seeds and fruit oil have been used for intestinal worms (Lust, 1974), and the rootbark as a purgative, emetic, and menstrual aid (Westbrook & Preacher, 1986).
    2) The seeds are sometimes used in rosaries (Turner & Szczawinski, 1991).
    3) The leaf or seed extracts have been used in the treatment of rheumatism, leprosy, scrofula, and skin conditions. Extracts have been investigated for their antiviral, antihelmenthic, and antitumor activity (Benencia et al, 1994).
    4) In Africa, plant extracts have been used to treat malaria, fevers, and venereal diseases (Benencia et al, 1994), and has been used for the treatment of leprosy, eczema, and asthma in South Africa (Oelrichs, 1983).
    5) MEDICINAL USE: It has been used as an antihelmenthic in China and the Island of Marituis, and has been used as a tonic and purgative in Algeria (Oelrichs, 1983). In China, it has been formulated for both oral and topical use (Phua et al, 2008).
    6) It is used as a fast-growing shade tree along roads and in villages in Indonesia (Bahri et al, 1992).

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: Melia azedarach, also known commonly as Chinaberry, is a tree that grows in Asia, Australia, Hawaii, Africa, South America, and parts of the southern United States. This is a tree that is grown as an ornamental or may be a weed in hedgerows. It may grow as tall as 50 feet. The leaves are compound and composed to 2 inch long leaflets that are lance-shaped with toothed edges. Each large leaf is about 1 to 3 feet long. The flowers are lilac, borne in large terminal clusters. They are about 1 inch across, fragrant and have 5 to 6 narrow petals. The fruit is a round, fleshy, thin skinned cherry-like berry which is green when immature, and yellow as it matures. It contains 3 to 5 smooth, black seeds.
    B) BACKGROUND: Chinaberry should not be confused with the Neem oil tree (Azadirachta indica formerly known as Melia azadirachta).
    C) USES: The plant has been used as an herbal medication. The seeds and fruit oil have been used for intestinal worms. It has been used as an antihelmenthic in China and the Island of Marituis, and has been used as a tonic and purgative in Algeria.
    D) TOXICITY: The fruit and bark are considered poisonous. It has been suggested that the entire plant may be toxic. Some genetic variations may exist producing variations in toxin content. The ripe fruit may be more toxic than the unripe fruit which is more toxic than other parts.
    E) TOXIN: Two toxins have been identified: Neurotoxin: tetranortriterpene; Gastrointestinal: an unidentified toxin.
    F) ROUTE: Potential human poisoning may occur after consuming 6 to 9 fruits, 30 to 40 seeds or 400 g of the bark of the Melia azedarach (ie, Chinaberry).
    G) WITH POISONING/EXPOSURE
    1) ONSET: Symptoms may begin within 1 hour or may be delayed several hours; and death, may occur within 12 to 24 hours. However, effects of chronic exposure appear variable and may be delayed up to weeks.
    2) ADVERSE EFFECTS: Gastrointestinal (vomiting, diarrhea) and CNS (eg, lethargy, coma, respiratory failure, seizures, paralysis) symptoms can occur. Based on limited reports other events have included generalized weakness, alteration in electrolytes (ie, hypokalemia, hypomagnesemia), elevated liver enzymes and creatinine kinase.
    0.2.4) HEENT
    A) Patients may grind their teeth. Mydriasis may be a late effect.
    0.2.6) RESPIRATORY
    A) Patients may have difficulty breathing, become cyanotic and can suffocate.
    0.2.7) NEUROLOGIC
    A) Reported effects can include: partial and total paralysis, ataxia and lack of coordination, sleeplessness, seizures, and a stuporous or comatose state.
    0.2.8) GASTROINTESTINAL
    A) Intense gastroenteritis, vomiting, and diarrhea may occur, which may produce hypovolemia.
    0.2.9) HEPATIC
    A) Mild elevations in liver enzymes have occurred in several adults after ingesting a tonic containing M. azedarach.
    B) Animal autopsy has shown fatty degeneration of the liver.
    0.2.10) GENITOURINARY
    A) Decreased urine output has been reported after ingestion of herbal leaf preparations. Animal autopsy has shown hyperemia of the kidneys if the animal survives a few days after ingestion.
    0.2.12) FLUID-ELECTROLYTE
    A) Severe thirst may be occur following ingestion. Severe, persistent vomiting and/or diarrhea may cause hypovolemia. Alterations in electrolytes (ie, hypokalemia, hypomagnesemia) may develop.
    0.2.14) DERMATOLOGIC
    A) Patients may be cold, sweaty, and pale.
    0.2.15) MUSCULOSKELETAL
    A) Myodegeneration muscular contractions and spasmodic quivering occurred in animals fed Melia extracts.
    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) At the time of this review, no data were available to assess the carcinogenic potential of this agent.
    0.2.22) OTHER
    A) An extract of the root bark from Melia azedarach exhibited cytotoxic activity in vitro.

Laboratory Monitoring

    A) There is no specific test for the toxins in this plant that are available in a clinical setting.
    B) Significant vomiting and/or diarrhea may require fluid and electrolyte monitoring. Heme test for blood in vomitus or stool as indicated.
    C) Monitor renal function, urine output, and liver function following significant ingestions.

Treatment Overview

    0.4.2) ORAL/PARENTERAL EXPOSURE
    A) MANAGEMENT OF MILD TO MODERATE TOXICITY
    1) Treatment is primarily symptomatic and supportive. Onset can occur within an hour or it can be variable. Significant vomiting and/or diarrhea may develop following exposure. Administer intravenous fluids and antiemetics as needed. Persistent altered mental status and seizure activity can indicate a more severe poisoning.
    B) MANAGEMENT OF SEVERE TOXICITY
    1) Treatment is primarily symptomatic and supportive. Monitor neurologic function closely. If seizures develop, treat with benzodiazepines.
    C) DECONTAMINATION
    1) PREHOSPITAL: GI decontamination is unlikely to be of benefit as spontaneous vomiting can occur following exposure. Based on limited data, CNS depression or seizure activity has occurred following exposure in some cases; therefore, prehospital decontamination should be avoided.
    2) HOSPITAL: Consider activated charcoal only after a significant ingestions if the patient is alert, not vomiting and can protect their airway.
    D) ANTIDOTE
    1) There is no specific antidote.
    E) AIRWAY MANAGEMENT
    1) Airway support is unlikely to be necessary following a minor or moderate exposure. Airway support may be necessary if a patient develops significant CNS depression, respiratory difficulty or seizure activity.
    F) ENHANCED ELIMINATION
    1) At the time of this review, there have been no reports addressing the utilization of extracorporeal elimination techniques in poisoning with this agent.
    G) PATIENT DISPOSITION
    1) HOME CRITERIA: An asymptomatic child or a child with mild vomiting following a "taste" ingestion of plant material can be monitored at home with adult supervision.
    2) OBSERVATION CRITERIA: Patients with CNS symptoms, persistent vomiting, those with deliberate abuse or a self harm ingestion should be referred to a healthcare facility. Patients should be observed until symptoms of intoxication have resolved.
    3) ADMISSION CRITERIA: Patients with persistent altered mental status, seizure activity or respiratory insufficiency should be admitted.
    4) CONSULT CRITERIA: Consult a poison center or medical toxicologist for assistance in managing severe poisonings or following a significant plant ingestion by a child.

Range Of Toxicity

    A) TOXICITY: The toxin content may vary based on genetic variations. Potential human poisoning may occur after consuming 6 to 9 fruits, 30 to 40 seeds or 400 g of the bark of the Melia azedarach (Chinaberry). In Argentina, the berries are considered harmless. However, analysis of toxins varies from plants collected within the same region. PEDIATRIC: A child died after ingesting 6 to 8 berries of an African strain.

Clinical Effects

Neurologic

    3.7.1) SUMMARY
    A) Reported effects can include: partial and total paralysis, ataxia and lack of coordination, sleeplessness, seizures, and a stuporous or comatose state.
    3.7.2) CLINICAL EFFECTS
    A) PARALYSIS
    1) WITH POISONING/EXPOSURE
    a) Partial and total paralysis have occurred (Lampe & McCann, 1985). Death may be due to paralysis (Lockey & Maxwell, 1986).
    1) Paralysis, respiratory failure and death may occur within 12 to 24 hours (Westbrooks & Preacher, 1986).
    B) NEUROLOGICAL FINDING
    1) WITH POISONING/EXPOSURE
    a) CASE REPORTS: In a series of 5 adults who consumed a tonic from the bark of M. azedarach for various conditions, one patient developed numbness over her lips and drooling along with general weakness and unsteady gait following the consumption of the tonic for 3 weeks. Her spouse also consumed the tonic and also developed drooling and generalized weakness. Both patients were hospitalized and fully recovered following supportive care (Phua et al, 2008).
    C) COMA
    1) WITH POISONING/EXPOSURE
    a) Patients may become stuporous or comatose (Schvartsman, 1979; Kiat, 1969; Lockey & Maxwell, 1986). Ingestion of herbal leaf preparations have caused lethargy (Perkins K & Payne W, 1978).
    D) ATAXIA
    1) WITH POISONING/EXPOSURE
    a) Ataxia may occur following an exposure (Lampe & McCann, 1985). It has also bee reported following ingestion of a tonic from the bark of M. azedarach used for various conditions (Phua et al, 2008).
    E) SEIZURE
    1) WITH POISONING/EXPOSURE
    a) Seizures have been observed (Lampe & McCann, 1985).
    F) INSOMNIA
    1) WITH POISONING/EXPOSURE
    a) Sleeplessness has been reported with some intoxications (Covacevich et al, 1987).

Gastrointestinal

    3.8.1) SUMMARY
    A) Intense gastroenteritis, vomiting, and diarrhea may occur, which may produce hypovolemia.
    3.8.2) CLINICAL EFFECTS
    A) VOMITING
    1) WITH POISONING/EXPOSURE
    a) Intense gastroenteritis and vomiting may develop (Lampe & McCann, 1985; Carratala, 1939). Oral irritation and bloody vomiting were observed after overdoses of herbal leaf preparations (Perkins K & Payne W, 1978).
    B) DIARRHEA
    1) WITH POISONING/EXPOSURE
    a) Diarrhea may develop (Phua et al, 2008). The combination of vomiting and diarrhea may produce hypovolemia (Lampe & McCann, 1985).

Summary Of Exposure

    A) DESCRIPTION: Melia azedarach, also known commonly as Chinaberry, is a tree that grows in Asia, Australia, Hawaii, Africa, South America, and parts of the southern United States. This is a tree that is grown as an ornamental or may be a weed in hedgerows. It may grow as tall as 50 feet. The leaves are compound and composed to 2 inch long leaflets that are lance-shaped with toothed edges. Each large leaf is about 1 to 3 feet long. The flowers are lilac, borne in large terminal clusters. They are about 1 inch across, fragrant and have 5 to 6 narrow petals. The fruit is a round, fleshy, thin skinned cherry-like berry which is green when immature, and yellow as it matures. It contains 3 to 5 smooth, black seeds.
    B) BACKGROUND: Chinaberry should not be confused with the Neem oil tree (Azadirachta indica formerly known as Melia azadirachta).
    C) USES: The plant has been used as an herbal medication. The seeds and fruit oil have been used for intestinal worms. It has been used as an antihelmenthic in China and the Island of Marituis, and has been used as a tonic and purgative in Algeria.
    D) TOXICITY: The fruit and bark are considered poisonous. It has been suggested that the entire plant may be toxic. Some genetic variations may exist producing variations in toxin content. The ripe fruit may be more toxic than the unripe fruit which is more toxic than other parts.
    E) TOXIN: Two toxins have been identified: Neurotoxin: tetranortriterpene; Gastrointestinal: an unidentified toxin.
    F) ROUTE: Potential human poisoning may occur after consuming 6 to 9 fruits, 30 to 40 seeds or 400 g of the bark of the Melia azedarach (ie, Chinaberry).
    G) WITH POISONING/EXPOSURE
    1) ONSET: Symptoms may begin within 1 hour or may be delayed several hours; and death, may occur within 12 to 24 hours. However, effects of chronic exposure appear variable and may be delayed up to weeks.
    2) ADVERSE EFFECTS: Gastrointestinal (vomiting, diarrhea) and CNS (eg, lethargy, coma, respiratory failure, seizures, paralysis) symptoms can occur. Based on limited reports other events have included generalized weakness, alteration in electrolytes (ie, hypokalemia, hypomagnesemia), elevated liver enzymes and creatinine kinase.

Heent

    3.4.1) SUMMARY
    A) Patients may grind their teeth. Mydriasis may be a late effect.
    3.4.2) HEAD
    A) TEETH GRINDING: Some intoxications have resulted in patients grinding their teeth (Covacevich et al, 1987; Oelrichs, 1983).
    3.4.3) EYES
    A) MYDRIASIS has been observed as a late effect and may be due to shock (Lampe & Fagerstrom, 1968).
    B) PTOSIS was observed in 2 patients following the ingestion of a tonic containing boiled bark of M. azedarach. Symptoms began within several days in one patient. Both patients completely recovered following supportive care (Phua et al, 2008).
    3.4.4) EARS
    A) MALIGNANT ULCERS have developed after forcing the fruit into the nose (Oelrichs, 1983).

Respiratory

    3.6.1) SUMMARY
    A) Patients may have difficulty breathing, become cyanotic and can suffocate.
    3.6.2) CLINICAL EFFECTS
    A) ACUTE RESPIRATORY INSUFFICIENCY
    1) WITH POISONING/EXPOSURE
    a) Patients may have difficulty breathing, become cyanotic and can suffocate (Steyn, 1934; Schvartsman, 1979).

Hepatic

    3.9.1) SUMMARY
    A) Mild elevations in liver enzymes have occurred in several adults after ingesting a tonic containing M. azedarach.
    B) Animal autopsy has shown fatty degeneration of the liver.
    3.9.2) CLINICAL EFFECTS
    A) LIVER ENZYMES ABNORMAL
    1) WITH THERAPEUTIC USE
    a) CASE REPORTS: In a series of 5 adults who consumed a tonic from the bark of M. azedarach for various conditions, 4 patients developed mild liver enzyme (ie, aspartate transaminase, alanine transaminase and alkaline phosphatase) elevations. Each patient fully recovered following supportive care (Phua et al, 2008).
    3.9.3) ANIMAL EFFECTS
    A) ANIMAL STUDIES
    1) LIVER FATTY
    a) Animal autopsy has shown fatty degeneration of the liver if the animals have lived a few days after ingestion (Kingsbury, 1964).

Genitourinary

    3.10.1) SUMMARY
    A) Decreased urine output has been reported after ingestion of herbal leaf preparations. Animal autopsy has shown hyperemia of the kidneys if the animal survives a few days after ingestion.
    3.10.2) CLINICAL EFFECTS
    A) TOXIC NEPHROPATHY
    1) WITH POISONING/EXPOSURE
    a) Decreased urine output has been reported after ingestion of herbal leaf preparations (Perkins K & Payne W, 1978).
    3.10.3) ANIMAL EFFECTS
    A) ANIMAL STUDIES
    1) NEPHROPATHY TOXIC
    a) Animal autopsy has shown hyperemia of the kidneys if the animal survives a few days after ingestion (Kingsbury, 1964).

Dermatologic

    3.14.1) SUMMARY
    A) Patients may be cold, sweaty, and pale.
    3.14.2) CLINICAL EFFECTS
    A) EXCESSIVE SWEATING
    1) WITH POISONING/EXPOSURE
    a) Patients may be cold, sweaty, and pale following intoxication (Lockey & Maxwell, 1986; Covacevich et al, 1987).

Musculoskeletal

    3.15.1) SUMMARY
    A) Myodegeneration muscular contractions and spasmodic quivering occurred in animals fed Melia extracts.
    3.15.2) CLINICAL EFFECTS
    A) SERUM CREATININE RAISED
    1) WITH POISONING/EXPOSURE
    a) CASE REPORTS: In a series of 5 adults who consumed a tonic from the bark of M. azedarach for various conditions, 3 patients developed mild elevations in creatinine kinase (range: 226 to 434 Units/liter). Each patient fully recovered following supportive care (Phua et al, 2008).
    B) ASTHENIA
    1) WITH POISONING/EXPOSURE
    a) CASE REPORTS: In a series of 5 adults who consumed a tonic from the bark of M. azedarach for various conditions, 3 patients complained of mild weakness and general malaise. Each patient fully recovered following supportive care (Phua et al, 2008).
    3.15.3) ANIMAL EFFECTS
    A) ANIMAL STUDIES
    1) MYOPATHY
    a) Myopathy was observed on histological exam in rats fed 0.25% dried leaves from Melia azedarach. Weakness and progressive hind-limb paralysis was also found (Bahri et al, 1991).
    2) ACUTE TOXICITY
    a) Rapid muscular contractions and spasmodic quivering (i.e. similar to shivering) developed in pigs fed an acute oral toxic dose of purified Melia toxin from berries (Oelrichs, 1983).

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) At the time of this review, no data were available to assess the carcinogenic potential of this agent.

Genotoxicity

    A) An extract of the root bark from Melia azedarach exhibited cytotoxic activity in vitro.
    B) Senanin-type liminoids isolated from Melia azedarach exhibited cytotoxic activity against P388 cells in vitro (Itokawa et al, 1995).

Laboratory Monitoring

Monitoring Parameters Levels

    4.1.1) SUMMARY
    A) There is no specific test for the toxins in this plant that are available in a clinical setting.
    B) Significant vomiting and/or diarrhea may require fluid and electrolyte monitoring. Heme test for blood in vomitus or stool as indicated.
    C) Monitor renal function, urine output, and liver function following significant ingestions.
    4.1.2) SERUM/BLOOD
    A) BLOOD/SERUM CHEMISTRY
    1) Monitor renal function, urine output, and liver function following a significant ingestion (Phua et al, 2008; Lampe & McCann, 1985).
    a) CASE REPORTS: In a series of 5 adults who consumed a tonic from the bark of M. azedarach for various conditions, 4 patients developed mild liver enzyme (ie, aspartate transaminase, alanine transaminase and alkaline phosphatase) elevations. Each patient fully recovered following supportive care (Phua et al, 2008).

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 with persistent altered mental status, seizure activity or respiratory insufficiency should be admitted.
    6.3.1.2) HOME CRITERIA/ORAL
    A) An asymptomatic child or a child with mild vomiting following a "taste" ingestion of plant material can be monitored at home with adult supervision.
    6.3.1.3) CONSULT CRITERIA/ORAL
    A) Consult a poison center or medical toxicologist for assistance in managing severe poisonings or following a significant plant ingestion by a child.
    6.3.1.5) OBSERVATION CRITERIA/ORAL
    A) Patients with CNS symptoms, persistent vomiting, those with deliberate abuse or a self harm ingestion should be referred to a healthcare facility. Patients should be observed until symptoms of intoxication have resolved.

Monitoring

    A) There is no specific test for the toxins in this plant that are available in a clinical setting.
    B) Significant vomiting and/or diarrhea may require fluid and electrolyte monitoring. Heme test for blood in vomitus or stool as indicated.
    C) Monitor renal function, urine output, and liver function following significant ingestions.

Oral Exposure

    6.5.1) PREVENTION OF ABSORPTION/PREHOSPITAL
    A) SUMMARY
    1) GI decontamination is unlikely to be of benefit as spontaneous vomiting can occur following exposure. Based on limited data, CNS depression or seizure activity has occurred following exposure in some cases; therefore, prehospital decontamination should be avoided.
    6.5.2) PREVENTION OF ABSORPTION
    A) SUMMARY
    1) Gastrointestinal decontamination is not recommended because of the potential for CNS depression and seizures.
    B) 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 primarily symptomatic and supportive. Onset can occur within an hour or it can be variable. Significant vomiting and/or diarrhea may develop following exposure. Administer intravenous fluids and antiemetics as needed. Persistent altered mental status and seizure activity can indicate a more severe poisoning.
    2) MANAGEMENT OF SEVERE TOXICITY
    a) Treatment is primarily symptomatic and supportive. Monitor neurologic function closely. If seizures develop, treat with benzodiazepines.
    B) MONITORING OF PATIENT
    1) Monitor fluid status and electrolyte balance in patients that develop significant vomiting and/or diarrhea.
    2) Monitor neurologic and respiratory function as indicated.
    3) Monitor renal function, urine output, and liver function following a significant ingestion.
    a) CASE REPORTS: In a series of 5 adults who consumed a tonic from the bark of M. azedarach for various conditions, 4 patients developed mild liver enzyme (ie, aspartate transaminase, alanine transaminase and alkaline phosphatase) elevations. Each patient fully recovered following supportive care (Phua et al, 2008).
    4) There is no specific test for the toxins in this plant that are available in a clinical setting.
    C) SEIZURE
    1) SUMMARY
    a) Attempt initial control with a benzodiazepine (eg, diazepam, lorazepam). If seizures persist or recur, administer phenobarbital or propofol.
    b) Monitor for respiratory depression, hypotension, and dysrhythmias. Endotracheal intubation should be performed in patients with persistent seizures.
    c) Evaluate for hypoxia, electrolyte disturbances, and hypoglycemia (or, if immediate bedside glucose testing is not available, treat with intravenous dextrose).
    2) DIAZEPAM
    a) ADULT DOSE: Initially 5 to 10 mg IV, OR 0.15 mg/kg IV up to 10 mg per dose up to a rate of 5 mg/minute; may be repeated every 5 to 20 minutes as needed (Brophy et al, 2012; Prod Info diazepam IM, IV injection, 2008; Manno, 2003).
    b) PEDIATRIC DOSE: 0.1 to 0.5 mg/kg IV over 2 to 5 minutes; up to a maximum of 10 mg/dose. May repeat dose every 5 to 10 minutes as needed (Loddenkemper & Goodkin, 2011; Hegenbarth & American Academy of Pediatrics Committee on Drugs, 2008).
    c) Monitor for hypotension, respiratory depression, and the need for endotracheal intubation. Consider a second agent if seizures persist or recur after repeated doses of diazepam .
    3) NO INTRAVENOUS ACCESS
    a) DIAZEPAM may be given rectally or intramuscularly (Manno, 2003). RECTAL DOSE: CHILD: Greater than 12 years: 0.2 mg/kg; 6 to 11 years: 0.3 mg/kg; 2 to 5 years: 0.5 mg/kg (Brophy et al, 2012).
    b) MIDAZOLAM has been used intramuscularly and intranasally, particularly in children when intravenous access has not been established. ADULT DOSE: 0.2 mg/kg IM, up to a maximum dose of 10 mg (Brophy et al, 2012). PEDIATRIC DOSE: INTRAMUSCULAR: 0.2 mg/kg IM, up to a maximum dose of 7 mg (Chamberlain et al, 1997) OR 10 mg IM (weight greater than 40 kg); 5 mg IM (weight 13 to 40 kg); INTRANASAL: 0.2 to 0.5 mg/kg up to a maximum of 10 mg/dose (Loddenkemper & Goodkin, 2011; Brophy et al, 2012). BUCCAL midazolam, 10 mg, has been used in adolescents and older children (5-years-old or more) to control seizures when intravenous access was not established (Scott et al, 1999).
    4) LORAZEPAM
    a) MAXIMUM RATE: The rate of intravenous administration of lorazepam should not exceed 2 mg/min (Brophy et al, 2012; Prod Info lorazepam IM, IV injection, 2008).
    b) ADULT DOSE: 2 to 4 mg IV initially; repeat every 5 to 10 minutes as needed, if seizures persist (Manno, 2003; Brophy et al, 2012).
    c) PEDIATRIC DOSE: 0.05 to 0.1 mg/kg IV over 2 to 5 minutes, up to a maximum of 4 mg/dose; may repeat in 5 to 15 minutes as needed, if seizures continue (Brophy et al, 2012; Loddenkemper & Goodkin, 2011; Hegenbarth & American Academy of Pediatrics Committee on Drugs, 2008; Sreenath et al, 2009; Chin et al, 2008).
    5) PHENOBARBITAL
    a) ADULT LOADING DOSE: 20 mg/kg IV at an infusion rate of 50 to 100 mg/minute IV. An additional 5 to 10 mg/kg dose may be given 10 minutes after loading infusion if seizures persist or recur (Brophy et al, 2012).
    b) Patients receiving high doses will require endotracheal intubation and may require vasopressor support (Brophy et al, 2012).
    c) PEDIATRIC LOADING DOSE: 20 mg/kg may be given as single or divided application (2 mg/kg/minute in children weighing less than 40 kg up to 100 mg/min in children weighing greater than 40 kg). A plasma concentration of about 20 mg/L will be achieved by this dose (Loddenkemper & Goodkin, 2011).
    d) REPEAT PEDIATRIC DOSE: Repeat doses of 5 to 20 mg/kg may be given every 15 to 20 minutes if seizures persist, with cardiorespiratory monitoring (Loddenkemper & Goodkin, 2011).
    e) MONITOR: For hypotension, respiratory depression, and the need for endotracheal intubation (Loddenkemper & Goodkin, 2011; Manno, 2003).
    f) SERUM CONCENTRATION MONITORING: Monitor serum concentrations over the next 12 to 24 hours. Therapeutic serum concentrations of phenobarbital range from 10 to 40 mcg/mL, although the optimal plasma concentration for some individuals may vary outside this range (Hvidberg & Dam, 1976; Choonara & Rane, 1990; AMA Department of Drugs, 1992).
    6) OTHER AGENTS
    a) If seizures persist after phenobarbital, propofol or pentobarbital infusion, or neuromuscular paralysis with general anesthesia (isoflurane) and continuous EEG monitoring should be considered (Manno, 2003). Other anticonvulsants can be considered (eg, valproate sodium, levetiracetam, lacosamide, topiramate) if seizures persist or recur; however, there is very little data regarding their use in toxin induced seizures, controlled trials are not available to define the optimal dosage ranges for these agents in status epilepticus (Brophy et al, 2012):
    1) VALPROATE SODIUM: ADULT DOSE: An initial dose of 20 to 40 mg/kg IV, at a rate of 3 to 6 mg/kg/minute; may give an additional dose of 20 mg/kg 10 minutes after loading infusion. PEDIATRIC DOSE: 1.5 to 3 mg/kg/minute (Brophy et al, 2012).
    2) LEVETIRACETAM: ADULT DOSE: 1000 to 3000 mg IV, at a rate of 2 to 5 mg/kg/min IV. PEDIATRIC DOSE: 20 to 60 mg/kg IV (Brophy et al, 2012; Loddenkemper & Goodkin, 2011).
    3) LACOSAMIDE: ADULT DOSE: 200 to 400 mg IV; 200 mg IV over 15 minutes (Brophy et al, 2012). PEDIATRIC DOSE: In one study, median starting doses of 1.3 mg/kg/day and maintenance doses of 4.7 mg/kg/day were used in children 8 years and older (Loddenkemper & Goodkin, 2011).
    4) TOPIRAMATE: ADULT DOSE: 200 to 400 mg nasogastric/orally OR 300 to 1600 mg/day orally divided in 2 to 4 times daily (Brophy et al, 2012).
    7) RECURRING SEIZURES
    a) RECURRING SEIZURES
    1) If seizures are not controlled by the above measures, patients will require endotracheal intubation, mechanical ventilation, continuous EEG monitoring, a continuous infusion of an anticonvulsant, and may require neuromuscular paralysis and vasopressor support. Consider continuous infusions of the following agents:
    a) MIDAZOLAM: ADULT DOSE: An initial dose of 0.2 mg/kg slow bolus, at an infusion rate of 2 mg/minute; maintenance doses of 0.05 to 2 mg/kg/hour continuous infusion dosing, titrated to EEG (Brophy et al, 2012). PEDIATRIC DOSE: 0.1 to 0.3 mg/kg followed by a continuous infusion starting at 1 mcg/kg/minute, titrated upwards every 5 minutes as needed (Loddenkemper & Goodkin, 2011).
    b) PROPOFOL: ADULT DOSE: Start at 20 mcg/kg/min with 1 to 2 mg/kg loading dose; maintenance doses of 30 to 200 mcg/kg/minute continuous infusion dosing, titrated to EEG; caution with high doses greater than 80 mcg/kg/minute in adults for extended periods of time (ie, longer than 48 hours) (Brophy et al, 2012); PEDIATRIC DOSE: IV loading dose of up to 2 mg/kg; maintenance doses of 2 to 5 mg/kg/hour may be used in older adolescents; avoid doses of 5 mg/kg/hour over prolonged periods because of propofol infusion syndrome (Loddenkemper & Goodkin, 2011); caution with high doses greater than 65 mcg/kg/min in children for extended periods of time; contraindicated in small children (Brophy et al, 2012).
    c) PENTOBARBITAL: ADULT DOSE: A loading dose of 5 to 15 mg/kg at an infusion rate of 50 mg/minute or lower; may administer additional 5 to 10 mg/kg. Maintenance dose of 0.5 to 5 mg/kg/hour continuous infusion dosing, titrated to EEG (Brophy et al, 2012). PEDIATRIC DOSE: A loading dose of 3 to 15 mg/kg followed by a maintenance dose of 1 to 5 mg/kg/hour (Loddenkemper & Goodkin, 2011).
    d) THIOPENTAL: ADULT DOSE: 2 to 7 mg/kg, at an infusion rate of 50 mg/minute or lower. Maintenance dose of 0.5 to 5 mg/kg/hour continuous infusing dosing, titrated to EEG (Brophy et al, 2012)
    2) Endotracheal intubation, mechanical ventilation, and vasopressors will be required (Brophy et al, 2012) and consultation with a neurologist is strongly advised.
    3) Neuromuscular paralysis (eg, rocuronium bromide, a short-acting nondepolarizing agent) may be required to avoid hyperthermia, severe acidosis, and rhabdomyolysis. If rhabdomyolysis is possible, avoid succinylcholine chloride, because of the risk of hyperkalemic-induced cardiac dysrhythmias. Continuous EEG monitoring is mandatory if neuromuscular paralysis is used (Manno, 2003).

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) SUMMARY
    1) At the time of this review, there have been no reports addressing the utilization of extracorporeal elimination techniques in poisoning with this agent.

Range Of Toxicity

Summary

    A) TOXICITY: The toxin content may vary based on genetic variations. Potential human poisoning may occur after consuming 6 to 9 fruits, 30 to 40 seeds or 400 g of the bark of the Melia azedarach (Chinaberry). In Argentina, the berries are considered harmless. However, analysis of toxins varies from plants collected within the same region. PEDIATRIC: A child died after ingesting 6 to 8 berries of an African strain.

Minimum Lethal Exposure

    A) SUMMARY
    1) The fruit and the bark are considered poisonous and there is great variability in the symptoms seen due to genetic variations of the plant (Nelson et al, 2007). The ingestion of as few as 6 to 8 berries have been fatal in some geographic locations, but in other areas the fruits may be eaten without harm. The ripe fruit is thought to be more toxic than the unripe fruit, which is more toxic than other parts of the plant (Bahri et al, 1992).
    2) Based on Chinese medical literature, human toxicity of Melia azedarach (Chinaberry) may occur with ingestion of 6 to 9 fruits, 30 to 40 seeds, or 400 g of the bark (Phua et al, 2008).
    3) Six to 8 berries have been said to cause the death of a young child (Hardin & Arena, 1974; Lockey & Maxwell, 1986); however, this was due to a strain that grows in Africa (Covacevich et al, 1987), and there is considerable variation in toxicity among strains.
    4) Fruit growing in one area of New South Wales were not found to be toxic, yet fruit from two other areas of New South Wales were found to contain toxins (Oelrichs, 1983).

Toxicity Information

    7.7.1) TOXICITY VALUES
    A) ANIMAL DATA
    1) LD50- (INTRAPERITONEAL)MOUSE:
    a) 250 mg/kg
    2) LD50- (ORAL)MOUSE:
    a) 16 mg/kg (Oelrichs, 1983)

Pharmacology Toxicology

Toxicologic Mechanism

    A) The seeds, leaves, bark, and roots contain a toxic tetranortriterpene neurotoxin that have been variously called azadarin, margosin or mangrovin (Oelrichs, 1983; Lampe & McCann, 1985; Lockey & Maxwell, 1986).
    B) The plant also contains a resin that acts on the gastrointestinal tract (Oelrichs, 1983).
    C) Toxic components include meliatoxins A1, A2, B1, and B2. They are tetranorterpinoids of the liminoid class (found in the fruits) and are responsible for nervous system effects. Meliatoxins may not be found in all samples of plant material (Orelichs, 1983).
    D) Cytotoxic and bitter liminoids have been isolated from Melia species (Itokawa et al, 1995; Srivastava, 1986).
    E) All parts contain a saponin, the leaves contain paraisine, and the fruit azaridine, and the bark margosine and tannin (Perkins K & Payne W, 1978).
    F) Salannin tetranorterpenoid found in several Melia species demonstrates biological activity against a variety of insects (Yamasaki et al, 1988; (Keeler & Tu, 1991).
    G) A liminoid extract from an Indian species of Melia demonstrated antibacterial activity against four organisms in vitro (Srivastava, 1986).
    H) Leaves of Melia collected in Argentina contain an antiviral factor which shows activity in vitro and in mice. The extract was shown to inhibit interferon production (Andrei et al, 1990; Andrei et al, 1986).

Animal Toxicology

Clinical Effects

    11.1.9) OVINE/SHEEP
    A) Sheep have a susceptibility similar to, but slightly less than, that of pigs. Symptoms seen are similar to those in humans (Kingsbury, 1964).
    11.1.10) PORCINE/SWINE
    A) Pigs are particularly sensitive to the effects of the toxins. Symptoms seen are similar to those in humans (Kingsbury, 1964).
    11.1.13) OTHER
    A) OTHER
    1) Poisoning has been seen in goats, cattle, fowl and other animals, but they seem to be less susceptible than pigs and sheep (Kingsbury, 1964).

Range Of Toxicity

    11.3.2) MINIMAL TOXIC DOSE
    A) SWINE
    1) Toxicity is approximately 0.5 percent of the animal's weight, but there is great variability (Kingsbury, 1964).
    B) SHEEP
    1) Toxicity is approximately 0.5 percent of the animal's weight, but there is great variability (Kingsbury, 1964).

Sources

    A) GENERAL
    1) Although animals have been poisoned in North America, the species of chinaberry found here seem to be less toxic than those in other places (Kingsbury, 1964).

References

General Bibliography

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