Contact Us    Contact Us     |     Feedback
MOBILE VIEW  | 

BERBERINE

Export To Excel

Classification   |    Detailed evidence-based information

Substances Included Synonyms

Therapeutic Toxic Class

    A) Berberine is a benzodioxoloquinolizine alkaloid found in several genera of plants, including the genera Berberis and Coptis. It is employed as a bitter stomachic in various herbs, and has had some use as an antibiotic and antimalarial and has been used for many years to treat diarrhea and dysentery.
    B) Berberine's physiological actions are relatively weak, but estimations on its toxicity vary considerably.

Specific Substances

    1) Berberine
    2) Umbelatine
    3) CAS 2086-83-1
    4) BERBERIN
    5) UMBELLATINE

Available Forms Sources

    A) SOURCES
    1) PLANTS - Berberine is found naturally in many plants, but especially in the Berberis, Hydrastis, and Mahonia genera in concentrations of 1% to 4% (Schulz, 1962; Osol & Farrar, 1955).
    2) This chemical accumulates preferentially in the root and stem bark where it appears as a yellow coloration (Frohme & Pfander, 1983).
    B) USES
    1) BERBERINE SULFATE - Berberine is used in its sulfate salt as an amoebicide against Entamoeba histolytica at a concentration of 0.5 to 1 mg/mL and has been shown to be effective at this concentration (Sabbaiah & Amin, 1967). Berberine has been used as a bitter or as a flavoring agent in food and alcoholic beverages (JEF Reynolds , 2000).
    2) HERBAL PRODUCTS - The Indian agent Daruharidra contains berberine and is used as a febrifuge, carminative, and skin ulcer dressing (Osol & Farrar, 1955). In traditional medicines this compound has been used for its antiinflammatory and antimicrobial effects (McGuffin et al, 1997).
    a) Representative Herbs Which Contain Berberine Include:
    1) Andira intermis (Duke, 1985)
    2) Argemone mexicana (Duke, 1974)
    3) Berberis vulgaris (Duke, 1985)
    4) Chelidonium majus (Duke, 1985)
    5) Coptis chinensis (McGuffin et al, 1997)
    6) Coptis groenlandica (McGuffin et al, 1997)
    7) Eschscholzia california (Watt & Breyer-Brandwijk, 1962)
    8) Hydrastis canadensis (Duke, 1985)
    9) Mahonia aquifolia (Duke, 1985)
    10) Mahonia nervosa (McGuffin et al, 1997)
    11) Mahonia repens (McGuffin et al, 1997)
    12) Papaver somniferum (Anon, 1979),
    13) Phellodendron amurense (McGuffin et al, 1997)
    14) Phellodendron chinense (McGuffin et al, 1997)
    15) Sanguinaria canadensis (Duke, 1985)
    3) Berberine's physiological actions are relatively weak (Osol & Farrar, 1955), but estimations on its toxicity vary considerably (Gosselin et al, 1984).

Overview

Life Support

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

Clinical Effects

    0.2.1) SUMMARY OF EXPOSURE
    A) Berberine is an isoquinoline alkaloid found in several genera of plants which has a fairly weak physiologic depressant action on the heart and CNS, and is a weak local anesthetic.
    0.2.4) HEENT
    A) Intense pain was produced when berberine was infiltrated in the conjunctiva of the eye.
    0.2.5) CARDIOVASCULAR
    A) Berberine has, in animal and human experiments, caused hypotension, bradycardia, and vasodilation. It appears to have both a direct action and an action via the vagal system.
    0.2.6) RESPIRATORY
    A) Respiratory depression has been seen with very large doses in animal experimentation.
    0.2.7) NEUROLOGIC
    A) Berberine has both central CNS depressant action and a weak local anesthetic action.
    0.2.8) GASTROINTESTINAL
    A) Berberine is a smooth muscle stimulant which causes stimulation of intestinal peristalsis and bile secretions.
    0.2.9) HEPATIC
    A) Berberine displaces bilirubin from human serum albumin in vitro. In animals berberine causes increased total serum bilirubin concentration.
    0.2.10) GENITOURINARY
    A) Animals exposed to lethal doses developed nephritis.
    B) Berberine is also thought to be a uterine smooth muscle relaxant.
    0.2.14) DERMATOLOGIC
    A) Pain, hyperpigmentation, flushing, and dermatitis have all been seen after dermal exposure or infiltration of berberine.
    0.2.20) REPRODUCTIVE
    A) Berberine is not recommended during pregnancy. There are no studies documenting effects of this agent used during pregnancy, however, berberine has shown paradoxical effects of uterine contractions as well as anticonvulsive activity in laboratory animals.
    0.2.21) CARCINOGENICITY
    A) Berberine appears to have anti-tumor activity. Kuo et al (1995) have demonstrated an induction of apoptosis by berberine on HL-60 promyelocytic leukemic cells by its ability to interact with DNA to form a berberine-DNA complex. These authors suggest that berberine may induce changes in DNA conformation by its interaction with DNA.

Laboratory Monitoring

    A) No laboratory values are useful in determining outcome or prognosis.

Treatment Overview

    0.4.2) ORAL/PARENTERAL EXPOSURE
    A) ACTIVATED CHARCOAL: Administer charcoal as a slurry (240 mL water/30 g charcoal). Usual dose: 25 to 100 g in adults/adolescents, 25 to 50 g in children (1 to 12 years), and 1 g/kg in infants less than 1 year old.
    B) EMESIS: Ipecac-induced emesis is not recommended because of the potential for CNS depression.
    C) All other treatment is symptomatic and supportive.
    0.4.4) EYE EXPOSURE
    A) DECONTAMINATION: 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, the patient should be seen in a healthcare facility.
    0.4.5) DERMAL EXPOSURE
    A) OVERVIEW
    1) DECONTAMINATION: Remove contaminated clothing and jewelry and place them in plastic bags. Wash exposed areas with soap and water for 10 to 15 minutes with gentle sponging to avoid skin breakdown. A physician may need to examine the area if irritation or pain persists (Burgess et al, 1999).

Range Of Toxicity

    A) No oral toxic dose has been established for berberine in humans. A massive overdose would be expected to result in CNS depressant effects.
    B) A therapeutic dose has ranged from 60 to 300 mg.
    C) The concentration of berberine in most plant products ranges from 1 to 4%.

Clinical Effects

Summary Of Exposure

    A) Berberine is an isoquinoline alkaloid found in several genera of plants which has a fairly weak physiologic depressant action on the heart and CNS, and is a weak local anesthetic.

Vital Signs

    3.3.3) TEMPERATURE
    A) Lowered body temperature was reported in animals given large doses of berberine (Sollmann, 1957).

Heent

    3.4.1) SUMMARY
    A) Intense pain was produced when berberine was infiltrated in the conjunctiva of the eye.
    3.4.3) EYES
    A) Intense pain was produced when berberine was infiltrated into the conjunctiva for the treatment of trachoma (Watt & Breyer-Brandwijk, 1962).

Cardiovascular

    3.5.1) SUMMARY
    A) Berberine has, in animal and human experiments, caused hypotension, bradycardia, and vasodilation. It appears to have both a direct action and an action via the vagal system.
    3.5.2) CLINICAL EFFECTS
    A) HYPOTENSIVE EPISODE
    1) Berberine may cause a transient drop in blood pressure (Kulkarni, 1972).
    B) VASODILATATION
    1) CASE SERIES - A dose of 0.2 mg/kg/min decreased both systemic and pulmonary vascular resistance in 12 human patients with refractive congestive heart failure (Marin-Neto et al, 1988).
    C) TORSADES DE POINTES
    1) CASE SERIES - Torsades de pointes-type ventricular tachycardia developed in 4 patients with refractory congestive heart failure 1 to 12 hours after receiving an infusion of 0.2 mg/kg/min for 30 minutes (Marin-Neto et al, 1988).
    3.5.3) ANIMAL EFFECTS
    A) ANIMAL STUDIES
    1) BRADYCARDIA
    a) Bradycardia was reported in dogs and cats at doses of 2 mg/kg (Chopra, 1932). Doses of 1 to 10 mg of berberine in animals stimulated heart muscle and increased coronary artery flow, but larger doses depressed the heart (Jang, 1941). Berberine appeared to have more specificity for the postsynaptic alpha-1 adrenoreceptors than presynaptic alpha-2 adrenoreceptors when studied in isolated animal organs (Olmez & Ilhan, 1992).
    b) RABBITS - Neto (1993) has demonstrated in the rabbit model a decrease, which is concentration-dependent, in the spontaneous frequency of sinoatrial cells which was accompanied by phase 4 depolarization depression. He also demonstrated a concentration-dependent increase in the action potential duration in canine Purkinje and ventricular muscles.
    2) VASODILATATION
    a) Vasodilation was reported in dogs and cats given 2 mg/kg. This action was caused both by a direct effect and by stimulation of the vagus (Osol & Farrar, 1955). Berberine was shown to cause a relaxing effect on isolated guinea pig aortic strips and cultured arterial smooth muscle cells, which would result in vasodilation and hypotension (Bova et al, 1992).

Respiratory

    3.6.1) SUMMARY
    A) Respiratory depression has been seen with very large doses in animal experimentation.
    3.6.3) ANIMAL EFFECTS
    A) ANIMAL STUDIES
    1) RESPIRATORY DEPRESSION
    a) Respiratory depression was seen in poisoned animals (Osol & Farrar, 1955), but generally only in doses high enough to cause respiratory arrest (Frohne & Pfander, 1984). Doses lower than this have had little respiratory effect.

Neurologic

    3.7.1) SUMMARY
    A) Berberine has both central CNS depressant action and a weak local anesthetic action.
    3.7.2) CLINICAL EFFECTS
    A) CENTRAL NERVOUS SYSTEM DEFICIT
    1) Berberine is a sedative in mice (Hartwell, 1971), and it is considered by most sources to be a central depressant in humans in large doses (Sollmann, 1957; Lewis, 1996).
    B) ABSENCE OF SENSATION
    1) Berberine was found in experiments to have a local anesthetic effect on mucous membranes and subcutaneous tissues (Seery & Bieter, 1940; Reynolds, 1982).

Gastrointestinal

    3.8.1) SUMMARY
    A) Berberine is a smooth muscle stimulant which causes stimulation of intestinal peristalsis and bile secretions.
    3.8.2) CLINICAL EFFECTS
    A) DRUG-INDUCED GASTROINTESTINAL DISTURBANCE
    1) Berberine is a smooth muscle stimulant that promotes intestinal peristalsis (Frohne & Pfander, 1984; Shin et al, 1993).
    3.8.3) ANIMAL EFFECTS
    A) ANIMAL STUDIES
    1) GASTROINTESTINAL DISORDER
    a) Berberine stimulates bile secretions in mice (Hartwell, 1971).
    b) Berberine has been shown to relax the guinea-pig isolated ileum (Olmez & Ilhan, 1992) and the isolated rat fundus (Lin & Chang, 1995).

Hepatic

    3.9.1) SUMMARY
    A) Berberine displaces bilirubin from human serum albumin in vitro. In animals berberine causes increased total serum bilirubin concentration.
    3.9.2) CLINICAL EFFECTS
    A) NEONATAL JAUNDICE
    1) Bilirubin toxicity resulting in kerniterus in Chinese infants was suspected to be due to berberine, contained in the Chinese herb, Coptis chinensis. Berberine displaces bilirubin from human serum albumin in vitro (Chan, 1993).
    3.9.3) ANIMAL EFFECTS
    A) ANIMAL STUDIES
    1) JAUNDICE
    a) In RATS intraperitoneal berberine administration for 7 days resulted in a significant increase in the fraction of unbound bilirubin, and an elevation of total bilirubin (Chan, 1993).

Genitourinary

    3.10.1) SUMMARY
    A) Animals exposed to lethal doses developed nephritis.
    B) Berberine is also thought to be a uterine smooth muscle relaxant.
    3.10.2) CLINICAL EFFECTS
    A) ATONY OF UTERUS
    1) Berberine is thought to be a uterine smooth muscle relaxant (Sollmann, 1957).
    3.10.3) ANIMAL EFFECTS
    A) ANIMAL STUDIES
    1) GLOMERULONEPHRITIS
    a) Lethal doses in animals caused hemorrhagic nephritis (Frohne & Pfander, 1984).

Dermatologic

    3.14.1) SUMMARY
    A) Pain, hyperpigmentation, flushing, and dermatitis have all been seen after dermal exposure or infiltration of berberine.
    3.14.2) CLINICAL EFFECTS
    A) DERMATITIS
    1) Several plant species containing berberine cause dermatitis, as does the wood and spines of these species. These reactions are thought to be due to berberine (Mitchell & Rook, 1979; Schwartz, 1938).
    B) PAIN
    1) When berberine was infiltrated into the skin for treatment of Leishmaniasis, it caused intense pain (Watt & Breyer-Brandwijk, 1962).
    C) VASODILATATION
    1) CASE SERIES - Flushing was seen in 2 of 12 patients receiving berberine infusions of 0.2 mg/kg/min for 30 minutes (Marin-Neto et al, 1988).
    3.14.3) ANIMAL EFFECTS
    A) ANIMAL STUDIES
    1) SKIN DISCOLORATION
    a) Hyperpigmentation was noted after intracutaneous injection in animals (Seery & Bieter, 1940).

Reproductive

    3.20.1) SUMMARY
    A) Berberine is not recommended during pregnancy. There are no studies documenting effects of this agent used during pregnancy, however, berberine has shown paradoxical effects of uterine contractions as well as anticonvulsive activity in laboratory animals.
    3.20.3) EFFECTS IN PREGNANCY
    A) PREGNANCY CATEGORY
    1) Berberine is not recommended during pregnancy. There are no studies documenting effects of this agent used during pregnancy, however, berberine has shown paradoxical effects of uterine contractions as well as anticonvulsive activity in laboratory animals (McGuffin et al, 1997).

Carcinogenicity

    3.21.1) IARC CATEGORY
    A) IARC Carcinogenicity Ratings for CAS2086-83-1 (International Agency for Research on Cancer (IARC), 2016; International Agency for Research on Cancer, 2015; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2010; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2010a; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2008; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2007; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2006; IARC, 2004):
    1) Not Listed
    3.21.2) SUMMARY/HUMAN
    A) Berberine appears to have anti-tumor activity. Kuo et al (1995) have demonstrated an induction of apoptosis by berberine on HL-60 promyelocytic leukemic cells by its ability to interact with DNA to form a berberine-DNA complex. These authors suggest that berberine may induce changes in DNA conformation by its interaction with DNA.

Genotoxicity

    A) Berberine appears to have anti-tumor activity. Kuo et al (1995) have demonstrated an induction of apoptosis by berberine on HL-60 promyelocytic leukemic cells by its ability to interact with DNA to form a berberine-DNA complex. These authors suggest that berberine may induce changes in DNA conformation by its interaction with DNA.

Laboratory Monitoring

Monitoring Parameters Levels

    4.1.1) SUMMARY
    A) No laboratory values are useful in determining outcome or prognosis.
    4.1.2) SERUM/BLOOD
    A) OTHER
    1) Berberine levels are not available as a standard hospital laboratory measurement.
    2) The effects of berberine are primarily on the cardiovascular and central nervous systems and do not alter laboratory values until near death.

Methods

    A) CHROMATOGRAPHY
    1) Chen & Chang (1995) describe a high-performance liquid chromatography (HPLC) method for the determination of berberine in plasma, urine and bile, which has high specificity, sensitivity, accuracy and reproducibility.

Treatment

Life Support

    A) Support respiratory and cardiovascular function.

Monitoring

    A) No laboratory values are useful in determining outcome or prognosis.

Oral Exposure

    6.5.1) PREVENTION OF ABSORPTION/PREHOSPITAL
    A) EMESIS/NOT RECOMMENDED -
    1) EMESIS: Ipecac-induced emesis is not recommended because of the potential for CNS depression.
    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) There is no specific antidote for berberine intoxication.
    2) The primary treatment is aggressive supportive care of cardiac and respiratory function.
    B) MONITORING OF PATIENT
    1) Since animals fatally poisoned with berberine developed nephritis, kidney function may need to be followed if large quantities have been ingested to evaluate the potential for damage in humans.

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 ABSORPTION
    1) Exposure through the skin is not a normal route of exposure for berberine, and only one reference mentioned that it may be absorbed through the skin to cause toxic reactions (Sax, 1984).
    2) Berberine usually leaves a yellow stain on the skin.
    B) OTHER
    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).

Range Of Toxicity

Summary

    A) No oral toxic dose has been established for berberine in humans. A massive overdose would be expected to result in CNS depressant effects.
    B) A therapeutic dose has ranged from 60 to 300 mg.
    C) The concentration of berberine in most plant products ranges from 1 to 4%.

Therapeutic Dose

    7.2.1) ADULT
    A) SPECIFIC SUBSTANCE
    1) BERBERIS ROOT - 1 to 2 grams has been used for emetic dose (Anon, 1983).
    2) BERBERINE (ALKALOID) - 60 to 300 milligrams has been used as an adult therapeutic dose (Osol & Farrar, 1955). Berberine has also been used against cholera in doses of up to 150 milligrams/day (Reynolds, 1982).

Maximum Tolerated Exposure

    A) GENERAL/SUMMARY
    1) No toxic dose has been established for berberine. A massive overdose would be expected to result in CNS depression (Lewis, 1996).
    2) Berberine is most often encountered in herbal or plant products. Concentration in the original plant is 1 to 4 percent.
    3) A therapeutic dose of 300 milligrams in an adult is contained within approximately 7.5 grams of a 4 percent berberine containing plant.
    B) ANIMAL DATA
    1) Oral toxic doses in animals have not been reported, but subcutaneous toxic to lethal doses have ranged from 18 to 100 milligrams/kilogram.

Workplace Standards

    A) ACGIH TLV Values for CAS2086-83-1 (American Conference of Governmental Industrial Hygienists, 2010):
    1) Not Listed

    B) NIOSH REL and IDLH Values for CAS2086-83-1 (National Institute for Occupational Safety and Health, 2007):
    1) Not Listed

    C) Carcinogenicity Ratings for CAS2086-83-1 :
    1) ACGIH (American Conference of Governmental Industrial Hygienists, 2010): Not Listed
    2) EPA (U.S. Environmental Protection Agency, 2011): Not Listed
    3) IARC (International Agency for Research on Cancer (IARC), 2016; International Agency for Research on Cancer, 2015; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2010; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2010a; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2008; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2007; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2006; IARC, 2004): Not Listed
    4) NIOSH (National Institute for Occupational Safety and Health, 2007): Not Listed
    5) MAK (DFG, 2002): Not Listed
    6) NTP (U.S. Department of Health and Human Services, Public Health Service, National Toxicology Project ): Not Listed

    D) OSHA PEL Values for CAS2086-83-1 (U.S. Occupational Safety, and Health Administration (OSHA), 2010):
    1) Not Listed

Toxicity Information

    7.7.1) TOXICITY VALUES
    A) LD50- (ORAL)MOUSE:
    1) 329 mg/kg (RTECS, 2000)
    B) LD50- (SUBCUTANEOUS)MOUSE:
    1) 18 mg/kg (Tatken & Lewis, 1983)
    2) 18 mg/kg (RTECS, 2000)

Pharmacology Toxicology

Pharmacologic Mechanism

    A) Berberine has been shown to have strong positive inotropic and peripheral resistance-lowering effects in dogs (Marin-Neto et al, 1988; Neto, 1993). In humans an infusion of 0.02 mg/kg per minute for 30 minutes reduced heart rate by 14% (Marin-Neto et al, 1988).
    B) Infusion of 0.2 mg/kg/min for 30 minutes produced (Marin-Neto et al, 1988):
    1) Decreased systemic vascular resistance (48%)
    2) Decreased pulmonary vascular resistance (41%)
    3) Decreased right atrium end-diastolic pressure (28%)
    4) Decreased left ventricular end-diastolic pressure (32%)
    5) Increased cardiac index (45%)
    6) Increased stroke index (45%)
    7) Increased LV ejection fraction (56%)
    C) Berberine is not thought to possess digitalis or adrenergic properties (Maroko et al, 1982).
    D) Berberine lowers peripheral vascular resistance and stimulates cardiac inotropism (Krol et al, 1982; Vik-Mo et al, 1983) Zalewski et al, 1983).
    E) Dogs poisoned with digitalis or aconitine were treated for their cardiac arrhythmias. Berberine antagonized these effects (Krol et al, 1982a; Ksiezycka et al, 1983; Wang et al, 1994). Wang et al (1994) proposes the mechanism to be suppression of delayed afterdepolarizations, which may also be in part due to decreased sodium influx.
    F) Berberine reduces the tonic contraction of the longitudinal muscle of the isolated rat gastric fundus. It is proposed that the major mechanism for this relaxant effect is the inhibition of extracellular calcium entry into the muscle (tonic phase) by berberine. At much higher doses, berberine may also prevent the mobilization of intracellular calcium (Lin & Chang, 1995).
    G) Berberine has been shown to increase ileal contractility by these possible mechanisms (Shin et al, 1993):
    1) Increased acetylcholine release from postganglionic parasympathetic nerve terminals
    2) Increased acetylcholine retention through inhibited cholinesterase activity
    3) Alpha 2-adrenoceptor blockade, possibly in the postganglionic parasympathetic nerve.

Toxicologic Mechanism

    A) Berberine is a weak local anesthetic, a central depressant in large doses, a cardiac depressant, vasodilator, anticonsulvant, and smooth muscle relaxant (Osol & Farrar, 1955; Shaffer, 1985) Chun et al, 1985).
    B) Berberine is also known to have antimicrobial properties (Lewis & Elvin-Lewis, 1983; Leung, 1980).
    C) Has a mild antitumor effect (Duke, 1985). Kuo et al (1995) have demonstrated an induction of apoptosis by berberine on HL-60 promyelocytic leukemic cells by its ability to interact with DNA to form a berberine-DNA complex. These authors suggest that berberine may induce changes in DNA conformation by its interaction with DNA.
    D) Berberine stimulates bile secretions in humans (Leung, 1980).

Physicochemical

Physical Characteristics

    A) Berberine can be white but usually yellow crystal or needle. It is thought there are 3 forms, the most common acts as a quaternary base. There is also a tautomeric pseudo-base and an imino aldehyde form (Osol & Farrar, 1955).

Molecular Weight

    A) BERBERINE: 336.39 (JEF Reynolds , 2000)
    B) BERBERINE SULFATE: 768.84 (Lewis, 1996)
    C) BERBERINE SULFATE TRIHYDRATE: 822.9 (Lewis, 1996)

References

General Bibliography

    1) 40 CFR 372.28: Environmental Protection Agency - Toxic Chemical Release Reporting, Community Right-To-Know, Lower thresholds for chemicals of special concern. National Archives and Records Administration (NARA) and the Government Printing Office (GPO). Washington, DC. Final rules current as of Apr 3, 2006.
    2) 40 CFR 372.65: Environmental Protection Agency - Toxic Chemical Release Reporting, Community Right-To-Know, Chemicals and Chemical Categories to which this part applies. National Archives and Records Association (NARA) and the Government Printing Office (GPO), Washington, DC. Final rules current as of Apr 3, 2006.
    3) 49 CFR 172.101 - App. B: Department of Transportation - Table of Hazardous Materials, Appendix B: List of Marine Pollutants. National Archives and Records Administration (NARA) and the Government Printing Office (GPO), Washington, DC. Final rules current as of Aug 29, 2005.
    4) 62 FR 58840: Notice of the National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances - Proposed AEGL Values, Environmental Protection Agency, NAC/AEGL Committee. National Archives and Records Administration (NARA) and the Government Publishing Office (GPO), Washington, DC, 1997.
    5) 65 FR 14186: Notice of the National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances - Proposed AEGL Values, Environmental Protection Agency, NAC/AEGL Committee. National Archives and Records Administration (NARA) and the Government Publishing Office (GPO), Washington, DC, 2000.
    6) 65 FR 39264: Notice of the National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances - Proposed AEGL Values, Environmental Protection Agency, NAC/AEGL Committee. National Archives and Records Administration (NARA) and the Government Publishing Office (GPO), Washington, DC, 2000.
    7) 65 FR 77866: Notice of the National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances - Proposed AEGL Values, Environmental Protection Agency, NAC/AEGL Committee. National Archives and Records Administration (NARA) and the Government Publishing Office (GPO), Washington, DC, 2000.
    8) 66 FR 21940: Notice of the National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances - Proposed AEGL Values, Environmental Protection Agency, NAC/AEGL Committee. National Archives and Records Administration (NARA) and the Government Publishing Office (GPO), Washington, DC, 2001.
    9) 67 FR 7164: Notice of the National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances - Proposed AEGL Values, Environmental Protection Agency, NAC/AEGL Committee. National Archives and Records Administration (NARA) and the Government Publishing Office (GPO), Washington, DC, 2002.
    10) 68 FR 42710: Notice of the National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances - Proposed AEGL Values, Environmental Protection Agency, NAC/AEGL Committee. National Archives and Records Administration (NARA) and the Government Publishing Office (GPO), Washington, DC, 2003.
    11) 69 FR 54144: Notice of the National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances - Proposed AEGL Values, Environmental Protection Agency, NAC/AEGL Committee. National Archives and Records Administration (NARA) and the Government Publishing Office (GPO), Washington, DC, 2004.
    12) AIHA: 2006 Emergency Response Planning Guidelines and Workplace Environmental Exposure Level Guides Handbook, American Industrial Hygiene Association, Fairfax, VA, 2006.
    13) 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.
    14) American Conference of Governmental Industrial Hygienists : ACGIH 2010 Threshold Limit Values (TLVs(R)) for Chemical Substances and Physical Agents and Biological Exposure Indices (BEIs(R)), American Conference of Governmental Industrial Hygienists, Cincinnati, OH, 2010.
    15) Anon: British Herbal Pharmacopoeia. Keighley: British Herbal Medicine Association, 1983.
    16) Bova S, Padrini R, & Goldman WF: On the mechanism of vasodilating action of berberine: possible role of inositol lipid signaling system. J Pharmacol & Experimental Therapeutics 1992; 261:318-323.
    17) Budavari S: The Merck Index, 12th ed, Merck & Company, Inc, Whitehouse Station, NJ, 1996.
    18) Burgess JL, Kirk M, Borron SW, et al: Emergency department hazardous materials protocol for contaminated patients. Ann Emerg Med 1999; 34(2):205-212.
    19) Chan E: Displacement of bilirubin from albumin by berberine. Biol Neonate 1993; 63:201-208.
    20) Chen CM & Chang HC: Determination of berberine in plasma, urine and bile by high-performance liquid chromatography. J Chromatography 1995; 665:117-123.
    21) Chopra: Indian J Med Res 1932; 19:1193.
    22) Chyka PA, Seger D, Krenzelok EP, et al: Position paper: Single-dose activated charcoal. Clin Toxicol (Phila) 2005; 43(2):61-87.
    23) DFG: List of MAK and BAT Values 2002, Report No. 38, Deutsche Forschungsgemeinschaft, Commission for the Investigation of Health Hazards of Chemical Compounds in the Work Area, Wiley-VCH, Weinheim, Federal Republic of Germany, 2002.
    24) 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.
    25) Das Gupta & Dikshit: Indian Med Gaz 1929; 64:67.
    26) Duke JA: Handbook of Medicinal Herbs, CRC Press, Boca Raton, FL, 1985.
    27) EPA: Search results for Toxic Substances Control Act (TSCA) Inventory Chemicals. US Environmental Protection Agency, Substance Registry System, U.S. EPA's Office of Pollution Prevention and Toxics. Washington, DC. 2005. Available from URL: http://www.epa.gov/srs/.
    28) Elliot CG, Colby TV, & Kelly TM: Charcoal lung. Bronchiolitis obliterans after aspiration of activated charcoal. Chest 1989; 96:672-674.
    29) FDA: Poison treatment drug product for over-the-counter human use; tentative final monograph. FDA: Fed Register 1985; 50:2244-2262.
    30) Fischl & Kussat: Zrschr ges exp. Med 1931; 78:805.
    31) Frohne P & Pfander HJ: A Colour Atlas of Poisonous Plants, Wolfe Publishing Ltd, London, UK, 1984.
    32) Golej J, Boigner H, Burda G, et al: Severe respiratory failure following charcoal application in a toddler. Resuscitation 2001; 49:315-318.
    33) Gosselin RE, Smith RP, & Hodge HC: Clinical Toxicology of Commercial Products, 5th ed, William & Wilkins, Baltimore, MD, 1984.
    34) Graff GR, Stark J, & Berkenbosch JW: Chronic lung disease after activated charcoal aspiration. Pediatrics 2002; 109:959-961.
    35) Guenther Skokan E, Junkins EP, & Corneli HM: Taste test: children rate flavoring agents used with activated charcoal. Arch Pediatr Adolesc Med 2001; 155:683-686.
    36) Harris CR & Filandrinos D: Accidental administration of activated charcoal into the lung: aspiration by proxy. Ann Emerg Med 1993; 22:1470-1473.
    37) Hartwell JL: Lloydia 1971; 34:103.
    38) IARC Working Group on the Evaluation of Carcinogenic Risks to Humans : IARC Monographs on the Evaluation of Carcinogenic Risks to Humans: 1,3-Butadiene, Ethylene Oxide and Vinyl Halides (Vinyl Fluoride, Vinyl Chloride and Vinyl Bromide), 97, International Agency for Research on Cancer, Lyon, France, 2008.
    39) IARC Working Group on the Evaluation of Carcinogenic Risks to Humans : IARC Monographs on the Evaluation of Carcinogenic Risks to Humans: Formaldehyde, 2-Butoxyethanol and 1-tert-Butoxypropan-2-ol, 88, International Agency for Research on Cancer, Lyon, France, 2006.
    40) IARC Working Group on the Evaluation of Carcinogenic Risks to Humans : IARC Monographs on the Evaluation of Carcinogenic Risks to Humans: Household Use of Solid Fuels and High-temperature Frying, 95, International Agency for Research on Cancer, Lyon, France, 2010a.
    41) IARC Working Group on the Evaluation of Carcinogenic Risks to Humans : IARC Monographs on the Evaluation of Carcinogenic Risks to Humans: Smokeless Tobacco and Some Tobacco-specific N-Nitrosamines, 89, International Agency for Research on Cancer, Lyon, France, 2007.
    42) IARC Working Group on the Evaluation of Carcinogenic Risks to Humans : IARC Monographs on the Evaluation of Carcinogenic Risks to Humans: Some Non-heterocyclic Polycyclic Aromatic Hydrocarbons and Some Related Exposures, 92, International Agency for Research on Cancer, Lyon, France, 2010.
    43) IARC: List of all agents, mixtures and exposures evaluated to date - IARC Monographs: Overall Evaluations of Carcinogenicity to Humans, Volumes 1-88, 1972-PRESENT. World Health Organization, International Agency for Research on Cancer. Lyon, FranceAvailable from URL: http://monographs.iarc.fr/monoeval/crthall.html. As accessed Oct 07, 2004.
    44) International Agency for Research on Cancer (IARC): IARC monographs on the evaluation of carcinogenic risks to humans: list of classifications, volumes 1-116. International Agency for Research on Cancer (IARC). Lyon, France. 2016. Available from URL: http://monographs.iarc.fr/ENG/Classification/latest_classif.php. As accessed 2016-08-24.
    45) International Agency for Research on Cancer: IARC Monographs on the Evaluation of Carcinogenic Risks to Humans. World Health Organization. Geneva, Switzerland. 2015. Available from URL: http://monographs.iarc.fr/ENG/Classification/. As accessed 2015-08-06.
    46) JEF Reynolds : Martindale: The Extra Pharmacopeia (Internet version). The Pharmaceutical Press. London, UK (Internet Version). Edition expires 2000; provided by Truven Health Analytics Inc., Greenwood Village, CO.
    47) Jang: J Pharmacol 1941; 71:178.
    48) Krol R, Zalewski A, & Cheung WM: Additive effects of berberine and ouabain on myocardial contractility (abstr). Clin Res 1982; 30:673-A.
    49) Krol R, Zalewski A, & Maroko PR: Beneficial effects of berberine, a new positive inotropic agent, on digitalis-induced ventricular arrhythmias (abstr). Circulation 1982a; 66(Suppl II):56.
    50) Ksiezycka E, Cheung WM, & Maroko PR: Antiarrhythmic effects of berberine on aconitine-induced ventricular and supraventricular arrhythmias (abstr). Clin Res 1983; 312:197-A.
    51) Kulkarni SK: Japan J Pharmacol 1972; 22:11.
    52) Leung AY: Encyclopedia of Common Natural Ingredients Used in Food, Drugs, and Cosmetics, John Wiley & Sons, New York, NY, 1980.
    53) Lewis RJ Sr: Sax's Dangerous Properties of Industrial Materials, 9th ed, Van Nostrand Reinhold, New York, NY, 1996.
    54) Lewis WH & Elvin-Lewis MPF: Contributions of herbology to modern medicine and dentistry. In: Keeler R & Tu A: Handbook of Natural Toxins, Vol 1, Plant & Fungal Toxins, Marcel Dekker, Inc, New York, 1983, pp 317.
    55) Lin WC & Chang HL: Relaxant effects of berberine on the rat fundus. Res Comm in Molecular Path & Pharmacology 1995; 90:333-346.
    56) Marin-Neto JA, Maciel BC, & Secches AL: Cardiovascular effects of berberine in patients with severe congestive heart failure. Clin Cardiol 1988; 11:253-260.
    57) Maroko PR, Zalewski A, & Krol R: Protoberberine alkaloids - a new family of inotropic agents (abstr). Circulation 1982; 66(suppl II):137.
    58) McGuffin M, Hobbs C, & Upton R: American Herbal Products Association's Botanical Safety Handbook, CRC Press, Boca Raton, FL, 1997.
    59) Mitchell J & Rook A: Botanical Dermatology, Greengrass, Vancouver, BC, 1979.
    60) NFPA: Fire Protection Guide to Hazardous Materials, 13th ed., National Fire Protection Association, Quincy, MA, 2002.
    61) NRC: Acute Exposure Guideline Levels for Selected Airborne Chemicals - Volume 1, Subcommittee on Acute Exposure Guideline Levels, Committee on Toxicology, Board on Environmental Studies and Toxicology, Commission of Life Sciences, National Research Council. National Academy Press, Washington, DC, 2001.
    62) NRC: Acute Exposure Guideline Levels for Selected Airborne Chemicals - Volume 2, Subcommittee on Acute Exposure Guideline Levels, Committee on Toxicology, Board on Environmental Studies and Toxicology, Commission of Life Sciences, National Research Council. National Academy Press, Washington, DC, 2002.
    63) NRC: Acute Exposure Guideline Levels for Selected Airborne Chemicals - Volume 3, Subcommittee on Acute Exposure Guideline Levels, Committee on Toxicology, Board on Environmental Studies and Toxicology, Commission of Life Sciences, National Research Council. National Academy Press, Washington, DC, 2003.
    64) NRC: Acute Exposure Guideline Levels for Selected Airborne Chemicals - Volume 4, Subcommittee on Acute Exposure Guideline Levels, Committee on Toxicology, Board on Environmental Studies and Toxicology, Commission of Life Sciences, National Research Council. National Academy Press, Washington, DC, 2004.
    65) Naradzay J & Barish RA: Approach to ophthalmologic emergencies. Med Clin North Am 2006; 90(2):305-328.
    66) National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for 1,2,3-Trimethylbenzene (Proposed). United States Environmental Protection Agency. Washington, DC. 2006k. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=090000648020d68a&disposition=attachment&contentType=pdf. As accessed 2010-08-12.
    67) National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for 1,2,4-Trimethylbenzene (Proposed). United States Environmental Protection Agency. Washington, DC. 2006m. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=090000648020d68a&disposition=attachment&contentType=pdf. As accessed 2010-08-16.
    68) National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for 1,2-Butylene Oxide (Proposed). United States Environmental Protection Agency. Washington, DC. 2008d. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=090000648083cdbb&disposition=attachment&contentType=pdf. As accessed 2010-08-12.
    69) National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for 1,2-Dibromoethane (Proposed). United States Environmental Protection Agency. Washington, DC. 2007g. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=09000064802796db&disposition=attachment&contentType=pdf. As accessed 2010-08-18.
    70) National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for 1,3,5-Trimethylbenzene (Proposed). United States Environmental Protection Agency. Washington, DC. 2006l. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=090000648020d68a&disposition=attachment&contentType=pdf. As accessed 2010-08-16.
    71) National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for 2-Ethylhexyl Chloroformate (Proposed). United States Environmental Protection Agency. Washington, DC. 2007b. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=090000648037904e&disposition=attachment&contentType=pdf. As accessed 2010-08-12.
    72) National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Acrylonitrile (Proposed). United States Environmental Protection Agency. Washington, DC. 2007c. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=090000648028e6a3&disposition=attachment&contentType=pdf. As accessed 2010-08-12.
    73) National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Adamsite (Proposed). United States Environmental Protection Agency. Washington, DC. 2007h. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=090000648020fd29&disposition=attachment&contentType=pdf. As accessed 2010-08-16.
    74) National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Agent BZ (3-quinuclidinyl benzilate) (Proposed). United States Environmental Protection Agency. Washington, DC. 2007f. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=09000064803ad507&disposition=attachment&contentType=pdf. As accessed 2010-08-18.
    75) National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Allyl Chloride (Proposed). United States Environmental Protection Agency. Washington, DC. 2008. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=090000648039d9ee&disposition=attachment&contentType=pdf. As accessed 2010-08-12.
    76) National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Aluminum Phosphide (Proposed). United States Environmental Protection Agency. Washington, DC. 2005b. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=090000648020c5ed&disposition=attachment&contentType=pdf. As accessed 2010-08-16.
    77) National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Arsenic Trioxide (Proposed). United States Environmental Protection Agency. Washington, DC. 2007m. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=0900006480220305&disposition=attachment&contentType=pdf. As accessed 2010-08-16.
    78) National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Automotive Gasoline Unleaded (Proposed). United States Environmental Protection Agency. Washington, DC. 2009a. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=0900006480a7cc17&disposition=attachment&contentType=pdf. As accessed 2010-08-12.
    79) National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Biphenyl (Proposed). United States Environmental Protection Agency. Washington, DC. 2005j. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=09000064801ea1b7&disposition=attachment&contentType=pdf. As accessed 2010-08-16.
    80) National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Bis-Chloromethyl Ether (BCME) (Proposed). United States Environmental Protection Agency. Washington, DC. 2006n. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=090000648022db11&disposition=attachment&contentType=pdf. As accessed 2010-08-16.
    81) National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Boron Tribromide (Proposed). United States Environmental Protection Agency. Washington, DC. 2008a. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=09000064803ae1d3&disposition=attachment&contentType=pdf. As accessed 2010-08-12.
    82) National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Bromine Chloride (Proposed). United States Environmental Protection Agency. Washington, DC. 2007d. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=090000648039732a&disposition=attachment&contentType=pdf. As accessed 2010-08-12.
    83) National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Bromoacetone (Proposed). United States Environmental Protection Agency. Washington, DC. 2008e. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=09000064809187bf&disposition=attachment&contentType=pdf. As accessed 2010-08-12.
    84) National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Calcium Phosphide (Proposed). United States Environmental Protection Agency. Washington, DC. 2005d. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=090000648020c5ed&disposition=attachment&contentType=pdf. As accessed 2010-08-16.
    85) National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Carbonyl Fluoride (Proposed). United States Environmental Protection Agency. Washington, DC. 2008b. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=09000064803ae328&disposition=attachment&contentType=pdf. As accessed 2010-08-12.
    86) National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Carbonyl Sulfide (Proposed). United States Environmental Protection Agency. Washington, DC. 2007e. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=090000648037ff26&disposition=attachment&contentType=pdf. As accessed 2010-08-12.
    87) National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Chlorobenzene (Proposed). United States Environmental Protection Agency. Washington, DC. 2008c. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=09000064803a52bb&disposition=attachment&contentType=pdf. As accessed 2010-08-12.
    88) National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Cyanogen (Proposed). United States Environmental Protection Agency. Washington, DC. 2008f. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=09000064809187fe&disposition=attachment&contentType=pdf. As accessed 2010-08-15.
    89) National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Dimethyl Phosphite (Proposed). United States Environmental Protection Agency. Washington, DC. 2009. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=0900006480a7cbf3&disposition=attachment&contentType=pdf. As accessed 2010-08-12.
    90) National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Diphenylchloroarsine (Proposed). United States Environmental Protection Agency. Washington, DC. 2007l. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=090000648020fd29&disposition=attachment&contentType=pdf. As accessed 2010-08-16.
    91) National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Ethyl Isocyanate (Proposed). United States Environmental Protection Agency. Washington, DC. 2008h. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=090000648091884e&disposition=attachment&contentType=pdf. As accessed 2010-08-15.
    92) National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Ethyl Phosphorodichloridate (Proposed). United States Environmental Protection Agency. Washington, DC. 2008i. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=0900006480920347&disposition=attachment&contentType=pdf. As accessed 2010-08-15.
    93) National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Ethylbenzene (Proposed). United States Environmental Protection Agency. Washington, DC. 2008g. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=09000064809203e7&disposition=attachment&contentType=pdf. As accessed 2010-08-15.
    94) National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Ethyldichloroarsine (Proposed). United States Environmental Protection Agency. Washington, DC. 2007j. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=090000648020fd29&disposition=attachment&contentType=pdf. As accessed 2010-08-16.
    95) National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Germane (Proposed). United States Environmental Protection Agency. Washington, DC. 2008j. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=0900006480963906&disposition=attachment&contentType=pdf. As accessed 2010-08-15.
    96) National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Hexafluoropropylene (Proposed). United States Environmental Protection Agency. Washington, DC. 2006. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=09000064801ea1f5&disposition=attachment&contentType=pdf. As accessed 2010-08-15.
    97) National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Ketene (Proposed). United States Environmental Protection Agency. Washington, DC. 2007. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=090000648020ee7c&disposition=attachment&contentType=pdf. As accessed 2010-08-15.
    98) National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Magnesium Aluminum Phosphide (Proposed). United States Environmental Protection Agency. Washington, DC. 2005h. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=090000648020c5ed&disposition=attachment&contentType=pdf. As accessed 2010-08-16.
    99) National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Magnesium Phosphide (Proposed). United States Environmental Protection Agency. Washington, DC. 2005g. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=090000648020c5ed&disposition=attachment&contentType=pdf. As accessed 2010-08-16.
    100) National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Malathion (Proposed). United States Environmental Protection Agency. Washington, DC. 2009k. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=09000064809639df&disposition=attachment&contentType=pdf. As accessed 2010-08-15.
    101) National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Mercury Vapor (Proposed). United States Environmental Protection Agency. Washington, DC. 2009b. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=0900006480a8a087&disposition=attachment&contentType=pdf. As accessed 2010-08-12.
    102) National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Methyl Isothiocyanate (Proposed). United States Environmental Protection Agency. Washington, DC. 2008k. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=0900006480963a03&disposition=attachment&contentType=pdf. As accessed 2010-08-15.
    103) National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Methyl Parathion (Proposed). United States Environmental Protection Agency. Washington, DC. 2008l. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=0900006480963a57&disposition=attachment&contentType=pdf. As accessed 2010-08-12.
    104) National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Methyl tertiary-butyl ether (Proposed). United States Environmental Protection Agency. Washington, DC. 2007a. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=09000064802a4985&disposition=attachment&contentType=pdf. As accessed 2010-08-15.
    105) National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Methylchlorosilane (Proposed). United States Environmental Protection Agency. Washington, DC. 2005. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=090000648020c5f4&disposition=attachment&contentType=pdf. As accessed 2010-08-15.
    106) National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Methyldichloroarsine (Proposed). United States Environmental Protection Agency. Washington, DC. 2007i. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=090000648020fd29&disposition=attachment&contentType=pdf. As accessed 2010-08-16.
    107) National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Methyldichlorosilane (Proposed). United States Environmental Protection Agency. Washington, DC. 2005a. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=090000648020c646&disposition=attachment&contentType=pdf. As accessed 2010-08-15.
    108) National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Nitrogen Mustard (HN1 CAS Reg. No. 538-07-8) (Proposed). United States Environmental Protection Agency. Washington, DC. 2006a. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=090000648020d6cb&disposition=attachment&contentType=pdf. As accessed 2010-08-15.
    109) National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Nitrogen Mustard (HN2 CAS Reg. No. 51-75-2) (Proposed). United States Environmental Protection Agency. Washington, DC. 2006b. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=090000648020d6cb&disposition=attachment&contentType=pdf. As accessed 2010-08-15.
    110) National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Nitrogen Mustard (HN3 CAS Reg. No. 555-77-1) (Proposed). United States Environmental Protection Agency. Washington, DC. 2006c. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=090000648020d6cb&disposition=attachment&contentType=pdf. As accessed 2010-08-15.
    111) National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Nitrogen Tetroxide (Proposed). United States Environmental Protection Agency. Washington, DC. 2008n. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=090000648091855b&disposition=attachment&contentType=pdf. As accessed 2010-08-12.
    112) National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Nitrogen Trifluoride (Proposed). United States Environmental Protection Agency. Washington, DC. 2009l. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=0900006480963e0c&disposition=attachment&contentType=pdf. As accessed 2010-08-12.
    113) National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Parathion (Proposed). United States Environmental Protection Agency. Washington, DC. 2008o. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=0900006480963e32&disposition=attachment&contentType=pdf. As accessed 2010-08-12.
    114) National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Perchloryl Fluoride (Proposed). United States Environmental Protection Agency. Washington, DC. 2009c. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=0900006480a7e268&disposition=attachment&contentType=pdf. As accessed 2010-08-12.
    115) National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Perfluoroisobutylene (Proposed). United States Environmental Protection Agency. Washington, DC. 2009d. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=0900006480a7e26a&disposition=attachment&contentType=pdf. As accessed 2010-08-15.
    116) National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Phenyl Isocyanate (Proposed). United States Environmental Protection Agency. Washington, DC. 2008p. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=090000648096dd58&disposition=attachment&contentType=pdf. As accessed 2010-08-12.
    117) National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Phenyl Mercaptan (Proposed). United States Environmental Protection Agency. Washington, DC. 2006d. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=090000648020cc0c&disposition=attachment&contentType=pdf. As accessed 2010-08-16.
    118) National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Phenyldichloroarsine (Proposed). United States Environmental Protection Agency. Washington, DC. 2007k. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=090000648020fd29&disposition=attachment&contentType=pdf. As accessed 2010-08-16.
    119) National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Phorate (Proposed). United States Environmental Protection Agency. Washington, DC. 2008q. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=090000648096dcc8&disposition=attachment&contentType=pdf. As accessed 2010-08-12.
    120) National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Phosgene (Draft-Revised). United States Environmental Protection Agency. Washington, DC. 2009e. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=0900006480a8a08a&disposition=attachment&contentType=pdf. As accessed 2010-08-12.
    121) National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Phosgene Oxime (Proposed). United States Environmental Protection Agency. Washington, DC. 2009f. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=0900006480a7e26d&disposition=attachment&contentType=pdf. As accessed 2010-08-12.
    122) National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Potassium Cyanide (Proposed). United States Environmental Protection Agency. Washington, DC. 2009g. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=0900006480a7cbb9&disposition=attachment&contentType=pdf. As accessed 2010-08-15.
    123) National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Potassium Phosphide (Proposed). United States Environmental Protection Agency. Washington, DC. 2005c. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=090000648020c5ed&disposition=attachment&contentType=pdf. As accessed 2010-08-16.
    124) National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Propargyl Alcohol (Proposed). United States Environmental Protection Agency. Washington, DC. 2006e. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=090000648020ec91&disposition=attachment&contentType=pdf. As accessed 2010-08-16.
    125) National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Selenium Hexafluoride (Proposed). United States Environmental Protection Agency. Washington, DC. 2006f. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=090000648020ec55&disposition=attachment&contentType=pdf. As accessed 2010-08-16.
    126) National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Silane (Proposed). United States Environmental Protection Agency. Washington, DC. 2006g. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=090000648020d523&disposition=attachment&contentType=pdf. As accessed 2010-08-16.
    127) National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Sodium Cyanide (Proposed). United States Environmental Protection Agency. Washington, DC. 2009h. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=0900006480a7cbb9&disposition=attachment&contentType=pdf. As accessed 2010-08-15.
    128) National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Sodium Phosphide (Proposed). United States Environmental Protection Agency. Washington, DC. 2005i. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=090000648020c5ed&disposition=attachment&contentType=pdf. As accessed 2010-08-16.
    129) National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Strontium Phosphide (Proposed). United States Environmental Protection Agency. Washington, DC. 2005f. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=090000648020c5ed&disposition=attachment&contentType=pdf. As accessed 2010-08-16.
    130) National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Sulfuryl Chloride (Proposed). United States Environmental Protection Agency. Washington, DC. 2006h. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=090000648020ec7a&disposition=attachment&contentType=pdf. As accessed 2010-08-16.
    131) National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Tear Gas (Proposed). United States Environmental Protection Agency. Washington, DC. 2008s. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=090000648096e551&disposition=attachment&contentType=pdf. As accessed 2010-08-12.
    132) National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Tellurium Hexafluoride (Proposed). United States Environmental Protection Agency. Washington, DC. 2009i. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=0900006480a7e2a1&disposition=attachment&contentType=pdf. As accessed 2010-08-12.
    133) National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Tert-Octyl Mercaptan (Proposed). United States Environmental Protection Agency. Washington, DC. 2008r. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=090000648096e5c7&disposition=attachment&contentType=pdf. As accessed 2010-08-12.
    134) National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Tetramethoxysilane (Proposed). United States Environmental Protection Agency. Washington, DC. 2006j. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=090000648020d632&disposition=attachment&contentType=pdf. As accessed 2010-08-17.
    135) National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Trimethoxysilane (Proposed). United States Environmental Protection Agency. Washington, DC. 2006i. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=090000648020d632&disposition=attachment&contentType=pdf. As accessed 2010-08-16.
    136) National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Trimethyl Phosphite (Proposed). United States Environmental Protection Agency. Washington, DC. 2009j. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=0900006480a7d608&disposition=attachment&contentType=pdf. As accessed 2010-08-12.
    137) National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Trimethylacetyl Chloride (Proposed). United States Environmental Protection Agency. Washington, DC. 2008t. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=090000648096e5cc&disposition=attachment&contentType=pdf. As accessed 2010-08-12.
    138) National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Zinc Phosphide (Proposed). United States Environmental Protection Agency. Washington, DC. 2005e. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=090000648020c5ed&disposition=attachment&contentType=pdf. As accessed 2010-08-16.
    139) National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for n-Butyl Isocyanate (Proposed). United States Environmental Protection Agency. Washington, DC. 2008m. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=09000064808f9591&disposition=attachment&contentType=pdf. As accessed 2010-08-12.
    140) National Institute for Occupational Safety and Health: NIOSH Pocket Guide to Chemical Hazards, U.S. Department of Health and Human Services, Centers for Disease Control and Prevention, Cincinnati, OH, 2007.
    141) National Research Council : Acute exposure guideline levels for selected airborne chemicals, 5, National Academies Press, Washington, DC, 2007.
    142) National Research Council: Acute exposure guideline levels for selected airborne chemicals, 6, National Academies Press, Washington, DC, 2008.
    143) National Research Council: Acute exposure guideline levels for selected airborne chemicals, 7, National Academies Press, Washington, DC, 2009.
    144) National Research Council: Acute exposure guideline levels for selected airborne chemicals, 8, National Academies Press, Washington, DC, 2010.
    145) Neto FR: Electropharmacological effects of berberine on canine cardiac Purkinje fibres and ventricular muscle and atrial muscle of the rabbit. Br J Pharmacol 1993; 108:534-537.
    146) None Listed: Position paper: cathartics. J Toxicol Clin Toxicol 2004; 42(3):243-253.
    147) Olmez E & Ilhan M: Evaluation of the a-adrenoceptor antagonistic action of berberine in isolated organs. Arzneimittel-Forschung 1992; 42:1095-1097.
    148) Osol A & Farrar GE: The Dispensatory of the United States of America, 25th ed, JB Lippincott Co, Philadelphia, PA, 1955.
    149) Peate WF: Work-related eye injuries and illnesses. Am Fam Physician 2007; 75(7):1017-1022.
    150) Pollack MM, Dunbar BS, & Holbrook PR: Aspiration of activated charcoal and gastric contents. Ann Emerg Med 1981; 10:528-529.
    151) Rau NR, Nagaraj MV, Prakash PS, et al: Fatal pulmonary aspiration of oral activated charcoal. Br Med J 1988; 297:918-919.
    152) Reynolds JEF: Martindale: The Extra Pharmacopoeia, 28th ed, The Pharmaceutical Press, London, UK, 1982.
    153) Sabbaiah TV & Amin AH: Nature 1967; 215:527.
    154) Sabir PT: Indian J Physiol Pharmacol 1971; 15:111.
    155) Sax NI: Dangerous Properties of Industrial Materials, 6th ed, Van Nostrand Reinhold Company, New York, NY, 1984.
    156) Schulz ER: Berberine in the common barberry (Berberis vulgaris). J Am Pharm Assoc 1962; 15:33.
    157) Schwartz WF: Foreign body (Barberry) dermatitis. Archs Derm Syph 1938; 37:872.
    158) Seery TM & Bieter RN: A contribution to the pharmacology of berberine. J Pharmacol 1940; 69:64.
    159) Shaffer JE: Inotropic and chronotropic activity of berberine on isolated guinea pigs atria. J Cardiovasc Pharmacol 1985; 7:307.
    160) Shin DH, Yu H, & Hsu WH: A paradoxical stimulatory effect of berberine on guinea-pig ileum contractility: possible involvement of acetylcholine release from the postganglionic parasympathetic nerve and cholinesterase inhibition. Life Sciences 1993; 53:1495-1500.
    161) Sollmann T: A Manual of Pharmacology, 8th ed, WB Saunders, Co, Philadelphia, PA, 1957.
    162) Spiller HA & Rogers GC: Evaluation of administration of activated charcoal in the home. Pediatrics 2002; 108:E100.
    163) Thakore S & Murphy N: The potential role of prehospital administration of activated charcoal. Emerg Med J 2002; 19:63-65.
    164) U.S. Department of Energy, Office of Emergency Management: Protective Action Criteria (PAC) with AEGLs, ERPGs, & TEELs: Rev. 26 for chemicals of concern. U.S. Department of Energy, Office of Emergency Management. Washington, DC. 2010. Available from URL: http://www.hss.doe.gov/HealthSafety/WSHP/Chem_Safety/teel.html. As accessed 2011-06-27.
    165) U.S. Department of Health and Human Services, Public Health Service, National Toxicology Project : 11th Report on Carcinogens. U.S. Department of Health and Human Services, Public Health Service, National Toxicology Program. Washington, DC. 2005. Available from URL: http://ntp.niehs.nih.gov/INDEXA5E1.HTM?objectid=32BA9724-F1F6-975E-7FCE50709CB4C932. As accessed 2011-06-27.
    166) U.S. Environmental Protection Agency: Discarded commercial chemical products, off-specification species, container residues, and spill residues thereof. Environmental Protection Agency's (EPA) Resource Conservation and Recovery Act (RCRA); List of hazardous substances and reportable quantities 2010b; 40CFR(261.33, e-f):77-.
    167) U.S. Environmental Protection Agency: Integrated Risk Information System (IRIS). U.S. Environmental Protection Agency. Washington, DC. 2011. Available from URL: http://cfpub.epa.gov/ncea/iris/index.cfm?fuseaction=iris.showSubstanceList&list_type=date. As accessed 2011-06-21.
    168) U.S. Environmental Protection Agency: List of Radionuclides. U.S. Environmental Protection Agency. Washington, DC. 2010a. Available from URL: http://www.gpo.gov/fdsys/pkg/CFR-2010-title40-vol27/pdf/CFR-2010-title40-vol27-sec302-4.pdf. As accessed 2011-06-17.
    169) U.S. Environmental Protection Agency: List of hazardous substances and reportable quantities. U.S. Environmental Protection Agency. Washington, DC. 2010. Available from URL: http://www.gpo.gov/fdsys/pkg/CFR-2010-title40-vol27/pdf/CFR-2010-title40-vol27-sec302-4.pdf. As accessed 2011-06-17.
    170) U.S. Environmental Protection Agency: The list of extremely hazardous substances and their threshold planning quantities (CAS Number Order). U.S. Environmental Protection Agency. Washington, DC. 2010c. Available from URL: http://www.gpo.gov/fdsys/pkg/CFR-2010-title40-vol27/pdf/CFR-2010-title40-vol27-part355.pdf. As accessed 2011-06-17.
    171) U.S. Occupational Safety and Health Administration: Part 1910 - Occupational safety and health standards (continued) Occupational Safety, and Health Administration's (OSHA) list of highly hazardous chemicals, toxics and reactives. Subpart Z - toxic and hazardous substances. CFR 2010 2010; Vol6(SEC1910):7-.
    172) U.S. Occupational Safety, and Health Administration (OSHA): Process safety management of highly hazardous chemicals. 29 CFR 2010 2010; 29(1910.119):348-.
    173) United States Environmental Protection Agency Office of Pollution Prevention and Toxics: Acute Exposure Guideline Levels (AEGLs) for Vinyl Acetate (Proposed). United States Environmental Protection Agency. Washington, DC. 2006. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=090000648020d6af&disposition=attachment&contentType=pdf. As accessed 2010-08-16.
    174) Vik-Mo H, Faria DB, & Cheung WH: Beneficial effects of berberine on left ventricular function in dogs with heart failure (abstr). Clin Res 1983; 31:224-A.
    175) Wang YX, Yao XJ, & Tan YH: Effects of berberine on delayed afterdepolarizations in ventricular muscles in vitro and in vivo. J Cardiovascular Pharmacology 1994; 23:716-722.
    176) Watt JM & Breyer-Brandwijk MG: The Medicinal and Poisonous Plants of Southern Africa, 2nd ed, E & S Livingstone, Edinburgh, UK, 1962.