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MONOSODIUM GLUTAMATE

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Classification   |    Detailed evidence-based information

Substances Included Synonyms

Therapeutic Toxic Class

    A) Monosodium glutamate (MSG) is a flavor enhancer.

Specific Substances

    1) Accent
    2) Ajinomoto
    3) alpha-Monosodium glutamate
    4) Anhydrous monosodium glutamate
    5) Chinese Seasoning
    6) E621
    7) Glutacyl
    8) Glutamic acid, monosodium salt, L-(+)-
    9) MSG
    10) Natrii Glutamas
    11) RL-50
    12) Sodium Glutamate
    13) Sodium hydrogen L-(+)-2-aminoglutarate monohydrate
    14) Vetsin
    15) Zest
    16) Chinese restaurant syndrome
    17) MSG (Monosodium glutamate)
    18) Sodium hydrogen L (+) alpha amino glutamate

Available Forms Sources

    A) FORMS
    1) In the grocery stores, MSG is sold as a fine, white crystal substance, similar in appearance to salt or sugar (Anon, 1995).
    2) LABEL LISTING: Foods and ingredients that contain glutamate as an inherent component (tomatoes, cheeses, meats, hydrolyzed protein products such as soy sauce, and autolyzed yeast extracts) are not required to list glutamate on the label. These ingredients are declared on the label by their common names. However, when MSG is added to food, the FDA requires "monosodium glutamate" to appear on the label. Other salts of glutamic acid (monopotassium glutamate, monoammonium glutamate) also have to be listed on labels and cannot appear under "spices", "natural flavoring", or other general terms (Anon, 2003).
    3) Anhydrous monosodium glutamate 29 grams or glutamic acid 25 grams is approximately equivalent to monosodium glutamate 32 grams (Sweetman, 2003).
    B) SOURCES
    1) Glutamate, a major building block of proteins, is released during breakdown of a protein molecule, and occurs naturally in many foods (eg; meat, milk, mushrooms, Parmesan cheese, and tomatoes) (Anon, 2003). Monosodium glutamate (MSG) is the monosodium salt of L-glutamic acid. It is produced by (HSDB, 2003; Anon, 2003):
    a) Fermentation of carbohydrate sources such as sugar beet molasses.
    b) Hydrolysis of vegetable proteins.
    c) Waste from beet-sugar molasses by acid hydrolysis.
    d) By action of Micrococcus glutamicus upon a carbohydrate and subsequent partial neutralization.
    2) To produce MSG, sugar beet products are mainly used in the US and in Europe; other carbohydrate sources (eg, sugar cane and tapioca) are often used in the Orient (HSDB, 2003).
    3) OCCUPATIONAL EXPOSURE: Dermal contact or inhalation of dusts at places where MSG is produced or used(HSDB, 2003).
    4) NON-OCCUPATIONAL EXPOSURE: Ingestion of MSG-containing foods (HSDB, 2003).
    C) USES
    1) MSG has the ability to increase salivation (HSDB, 2003). It has been used for many years as a flavor enhancer for a variety of foods such as Asian cuisines, canned vegetables, soups, and processed meats (Anon, 2003; HSDB, 2003). It has been estimated that the average daily intake of MSG is 0.3 to 1.0 grams in industrialized countries(Geha et al, 2000; Prawirohardjone et al, 2000).
    2) MSG has been used to treat patients with hyperammonemia in conditions such as hepatic encephalopathy. In the US, MSG has been used as a swine feed additive(HSDB, 2003).

Overview

Life Support

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

Clinical Effects

    0.2.1) SUMMARY OF EXPOSURE
    A) USES: Monosodium glutamate (MSG) has the ability to increase salivation. It has been used as a flavor enhancer for a variety of foods such as Asian cuisines, canned vegetables, soups, and processed meats. It has also been used to treat patients with hyperammonemia in conditions such as hepatic encephalopathy. It has been estimated that the average daily intake of MSG is 0.3 to 1 g in industrialized countries.
    B) DESCRIPTION: Glutamic acid, or glutamate, is a major "building block" of many proteins in foods, such as cheese, meat, pea, mushrooms, and milk. MSG is the monosodium salt of L-glutamic acid. Some glutamate is present in foods in a "free" form, not bound with other amino acids. It is only in this free form that glutamate can enhance a food's flavor. Part of the flavor-enhancing effect of tomatoes, certain cheeses, and fermented or hydrolyzed protein products is due to the presence of free glutamate.
    C) TOXICOLOGY: MSG SYMPTOM COMPLEX OR CHINESE RESTAURANT SYNDROME (CRS): Although several mechanisms have been proposed to explain CRS, none have been proven. Some of the following proposed mechanisms are listed: (1) The stimulation of peripheral receptors. (2) CRS was a form of acetylcholinosis: In one study, it was noted that the symptoms of CRS were similar to those observed after acetylcholine use. Glutamate can be converted to acetylcholine via the tricarboxylic acid (TCA) cycle, and drugs affecting the cholinergic mechanisms could modulate CRS symptoms. (3) CRS may be a manifestation of esophageal irritation. (4) Chinese meals increase plasma sodium levels, causing CRS. (5) Vitamin B6 deficiency in individuals may cause CRS. (6) CRS may be caused by histamine; In one study, it was found that some Chinese meals could contain levels of histamine close to the toxic threshold established by the FDA for histamine in foods.
    D) EPIDEMIOLOGY: Exposure is common. Severe toxicity is rare.
    E) WITH POISONING/EXPOSURE
    1) MSG SYMPTOM COMPLEX OR CHINESE RESTAURANT SYNDROME: Following the consumption of a meal with MSG, patients have reported one or more symptoms of a complex which includes headache, nausea, vomiting, abdominal pain, weakness, dizziness, syncope, flushing, tingling, lacrimation, sweating, tightness of face and neck, burning or pressure in the chest often radiating to the neck and arms, heartburn, and gastric distress. Supraventricular and ventricular tachycardia have also been reported. However, there is inadequate data to determine if MSG may have been a factor.
    0.2.20) REPRODUCTIVE
    A) In animal studies, MSG was not teratogenic. Glutamate crosses the placental barrier at a rate slower than that of simple diffusion; however, due to rapid metabolism of glutamate to glucose and lactate within the placenta, fetal glutamate plasma concentrations are much lower than maternal glutamate plasma concentrations.

Laboratory Monitoring

    A) No specific laboratory tests are necessary unless otherwise clinically indicated.
    B) Plasma concentrations are not readily available or clinically useful in the management of overdose.
    C) Monitor vital signs and mental status in symptomatic patients.
    D) Monitor serum electrolytes in patients with significant vomiting and/or diarrhea.

Treatment Overview

    0.4.2) ORAL/PARENTERAL EXPOSURE
    A) MANAGEMENT OF TOXICITY
    1) MANAGEMENT OF TOXICITY: Treatment is symptomatic and supportive. Toxicity is very unlikely. Correct any significant fluid and/or electrolyte abnormalities in patients with severe diarrhea and/or vomiting. In patients with acute allergic reaction, oxygen therapy, bronchodilators, diphenhydramine, corticosteroids, vasopressors and epinephrine may be required.
    B) DECONTAMINATION
    1) Gastrointestinal decontamination is generally not indicated after an acute ingestion. Toxicity is very unlikely.
    C) AIRWAY MANAGEMENT
    1) Ensure adequate ventilation and perform endotracheal intubation early in patients with severe allergic reactions or respiratory distress.
    D) ANTIDOTE
    1) None.
    E) ENHANCED ELIMINATION PROCEDURE
    1) There is no information regarding the effectiveness of hemodialysis or hemoperfusion for the removal of MSG from plasma.
    F) PATIENT DISPOSITION
    1) HOME CRITERIA: A patient with an inadvertent exposure, that remains asymptomatic can be managed at home.
    2) OBSERVATION CRITERIA: Symptomatic patients should be monitored until they are clearly improving and clinically stable.
    3) ADMISSION CRITERIA: Patients with severe symptoms despite treatment should be admitted.
    4) CONSULT CRITERIA: Consult a regional poison center or medical toxicologist for assistance in managing patients with severe toxicity or in whom the diagnosis is not clear.
    G) PITFALLS
    1) When managing a suspected overdose, the possibility of multidrug involvement should be considered. Missing an ingestion of another chemical or other possible etiologies for a patient’s symptoms. History of exposure may be difficult to obtain in some settings.
    H) DIFFERENTIAL DIAGNOSIS
    1) Includes other agents that may cause hypersensitivity reactions.

Range Of Toxicity

    A) TOXICITY: Flushing, facial pressure, chest pain, headache, and nausea have been reported in patients following the ingestion of food containing MSG. Patients usually experience these symptoms within an hour of eating 3 g or more of MSG on an empty stomach. In one study, very high oral doses of glutamate (147 g/day) given to adult humans as the sole source of nonessential nitrogen for 2 to 6 weeks was tolerated, with no neurological changes. In other studies, doses 60 to 150 mg MSG/kg body weight were also tolerated.

Clinical Effects

Summary Of Exposure

    A) USES: Monosodium glutamate (MSG) has the ability to increase salivation. It has been used as a flavor enhancer for a variety of foods such as Asian cuisines, canned vegetables, soups, and processed meats. It has also been used to treat patients with hyperammonemia in conditions such as hepatic encephalopathy. It has been estimated that the average daily intake of MSG is 0.3 to 1 g in industrialized countries.
    B) DESCRIPTION: Glutamic acid, or glutamate, is a major "building block" of many proteins in foods, such as cheese, meat, pea, mushrooms, and milk. MSG is the monosodium salt of L-glutamic acid. Some glutamate is present in foods in a "free" form, not bound with other amino acids. It is only in this free form that glutamate can enhance a food's flavor. Part of the flavor-enhancing effect of tomatoes, certain cheeses, and fermented or hydrolyzed protein products is due to the presence of free glutamate.
    C) TOXICOLOGY: MSG SYMPTOM COMPLEX OR CHINESE RESTAURANT SYNDROME (CRS): Although several mechanisms have been proposed to explain CRS, none have been proven. Some of the following proposed mechanisms are listed: (1) The stimulation of peripheral receptors. (2) CRS was a form of acetylcholinosis: In one study, it was noted that the symptoms of CRS were similar to those observed after acetylcholine use. Glutamate can be converted to acetylcholine via the tricarboxylic acid (TCA) cycle, and drugs affecting the cholinergic mechanisms could modulate CRS symptoms. (3) CRS may be a manifestation of esophageal irritation. (4) Chinese meals increase plasma sodium levels, causing CRS. (5) Vitamin B6 deficiency in individuals may cause CRS. (6) CRS may be caused by histamine; In one study, it was found that some Chinese meals could contain levels of histamine close to the toxic threshold established by the FDA for histamine in foods.
    D) EPIDEMIOLOGY: Exposure is common. Severe toxicity is rare.
    E) WITH POISONING/EXPOSURE
    1) MSG SYMPTOM COMPLEX OR CHINESE RESTAURANT SYNDROME: Following the consumption of a meal with MSG, patients have reported one or more symptoms of a complex which includes headache, nausea, vomiting, abdominal pain, weakness, dizziness, syncope, flushing, tingling, lacrimation, sweating, tightness of face and neck, burning or pressure in the chest often radiating to the neck and arms, heartburn, and gastric distress. Supraventricular and ventricular tachycardia have also been reported. However, there is inadequate data to determine if MSG may have been a factor.

Cardiovascular

    3.5.2) CLINICAL EFFECTS
    A) CONDUCTION DISORDER OF THE HEART
    1) WITH POISONING/EXPOSURE
    a) MSG-induced tachycardia has been reported in some patients (Goldberg, 1982; Freed & Carter, 1982; Gann, 1977).
    b) CASE REPORT: A healthy 36-year-old man developed ventricular tachycardia following the consumption of wonton soup with MSG. However, there is inadequate data to determine if MSG may have been a factor(Gann, 1977).
    c) CASE REPORT: A 42-year-old female developed weakness, flushing, headache, palpitations, chest discomfort, mild nausea and anxiety 30 minutes after ingesting 2.5 cans of wonton soup with MSG. An ECG revealed atrial fibrillation with a ventricular rate of 160 bpm (Goldberg, 1982).
    B) CHEST PAIN
    1) WITH POISONING/EXPOSURE
    a) MSG Symptom Complex or Chinese Restaurant Syndrome: Following the consumption of a meal with MSG, patients have reported one or more symptoms of a complex which includes weakness, dizziness, syncope, flushing, tingling, lacrimation, sweating, headache, tightness of face and neck, burning or pressure in the chest often radiating to the neck and arms, heartburn, and gastric distress (Sweetman, 2003; Yang et al, 1997; Goldberg, 1982).
    C) SYNCOPE
    1) WITH POISONING/EXPOSURE
    a) MSG Symptom Complex or Chinese Restaurant Syndrome: Following the consumption of a meal with MSG, patients have reported one or more symptoms of a complex which includes headache, weakness, dizziness, syncope, flushing, tingling, lacrimation, sweating, tightness of face and neck, burning or pressure in the chest often radiating to the neck and arms, heartburn, and gastric distress (Sweetman, 2003; Yang et al, 1997; Goldberg, 1982).

Respiratory

    3.6.2) CLINICAL EFFECTS
    A) ASTHMA
    1) WITH POISONING/EXPOSURE
    a) Although two studies have reported MSG-induced asthma attacks in asthmatic patients (Allen et al, 1987; Moneret-Vautrin, 1987), four additional studies could not confirm their results; reviewed in (Stevenson, 2000).

Neurologic

    3.7.2) CLINICAL EFFECTS
    A) HEADACHE
    1) WITH POISONING/EXPOSURE
    a) MSG Symptom Complex or Chinese Restaurant Syndrome: Following the consumption of a meal with MSG, patients have reported one or more symptoms of a complex which includes weakness, dizziness, syncope, flushing, tingling, lacrimation, sweating, headache, tightness of face and neck, burning or pressure in the chest often radiating to the neck and arms, heartburn, and gastric distress (Sweetman, 2003; Yang et al, 1997; Scopp, 1991; Goldberg, 1982).
    b) Individuals with vitamin B6 deficiency may experience headache, weakness, stiffness, and heartburn following the acute ingestion of excessive MSG (Ebadi et al, 1982).
    c) CASE REPORT: A 3-year-old girl developed confusion, slurred speech, slight ataxia, headache, nausea, vomiting and abdominal pain after eating Chinese food (Cochran & Cochran, 1984).
    B) ASTHENIA
    1) WITH POISONING/EXPOSURE
    a) MSG Symptom Complex or Chinese Restaurant Syndrome: Following the consumption of a meal with MSG, patients have reported one or more symptoms of a complex which includes weakness, dizziness, syncope, flushing, tingling, lacrimation, sweating, headache, tightness of face and neck, burning or pressure in the chest often radiating to the neck and arms, heartburn, and gastric distress (Yang et al, 1997; Goldberg, 1982).
    b) Individuals with vitamin B6 deficiency may experience headache, weakness, stiffness, and heartburn following the acute ingestion of excessive MSG (Ebadi et al, 1982).
    C) NEUROPATHY
    1) WITH POISONING/EXPOSURE
    a) CASE REPORT: Neuropathy (paresthesia of hands and feet) due to MSG intolerance has been reported in some patients (Freed & Carter, 1982).
    D) CLOUDED CONSCIOUSNESS
    1) WITH POISONING/EXPOSURE
    a) CASE REPORT: A 3-year-old girl developed confusion, slurred speech, slight ataxia, headache, nausea, vomiting and abdominal pain after eating Chinese food (Cochran & Cochran, 1984).
    E) ATAXIA
    1) WITH POISONING/EXPOSURE
    a) CASE REPORT: A 3-year-old girl developed confusion, slurred speech, slight ataxia, headache, nausea, vomiting and abdominal pain after eating Chinese food (Cochran & Cochran, 1984).

Gastrointestinal

    3.8.2) CLINICAL EFFECTS
    A) HEARTBURN
    1) WITH POISONING/EXPOSURE
    a) MSG Symptom Complex or Chinese Restaurant Syndrome: Following the consumption of a meal with MSG, patients have reported one or more symptoms of a complex which includes weakness, dizziness, syncope, flushing, tingling, lacrimation, sweating, headache, tightness of face and neck, burning or pressure in the chest often radiating to the neck and arms, heartburn, and gastric distress (Goldberg, 1982; Yang et al, 1997).
    b) Individuals with vitamin B6 deficiency may experience headache, weakness, stiffness, and heartburn following the acute ingestion of excessive MSG(Ebadi et al, 1982).
    B) ABDOMINAL PAIN
    1) WITH POISONING/EXPOSURE
    a) CASE REPORT: An 18-month-old boy developed abdominal pain, extreme irritability and flushing 10 minutes after ingesting Chinese noodles and wonton soup with MSG (Asnes, 1980).
    b) CASE REPORT: A 3-year-old girl developed confusion, slurred speech, slight ataxia, headache, nausea, vomiting and abdominal pain after eating Chinese food (Cochran & Cochran, 1984).
    C) NAUSEA AND VOMITING
    1) WITH POISONING/EXPOSURE
    a) Nausea and vomiting have been reported in some patients following the ingestion of food with MSG (Sweetman, 2003; Cochran & Cochran, 1984).
    b) CASE REPORT: A 3-year-old girl developed confusion, slurred speech, slight ataxia, headache, nausea, vomiting and abdominal pain after eating Chinese food (Cochran & Cochran, 1984).

Genitourinary

    3.10.2) CLINICAL EFFECTS
    A) INCONTINENCE
    1) WITH POISONING/EXPOSURE
    a) CASE REPORT: A 9-year-old boy experienced bladder and bowel incontinence and intermittent hyperactivity after eating meals with MSG. He recovered fully after being placed on a diet free of MSG (Asnes, 1980).

Dermatologic

    3.14.2) CLINICAL EFFECTS
    A) URTICARIA
    1) WITH POISONING/EXPOSURE
    a) In one study, it was suggested that MSG is an unusual (less than 3% at most) exacerbant of chronic idiopathic urticaria (Simon, 2000).
    B) FLUSHING
    1) WITH POISONING/EXPOSURE
    a) MSG Symptom Complex or Chinese Restaurant Syndrome: Following the consumption of a meal with MSG, patients have reported one or more symptoms of a complex which includes weakness, dizziness, syncope, flushing, tingling, lacrimation, sweating, headache, tightness of face and neck, burning or pressure in the chest often radiating to the neck and arms, heartburn, and gastric distress (Sweetman, 2003; Yang et al, 1997; Goldberg, 1982).
    b) CASE REPORT: An 18-month-old boy developed abdominal pain, extreme irritability and flushing 10 minutes after ingesting Chinese noodles and wonton soup with MSG (Asnes, 1980).
    C) EXCESSIVE SWEATING
    1) WITH POISONING/EXPOSURE
    a) MSG Symptom Complex or Chinese Restaurant Syndrome: Following the consumption of a meal with MSG, patients have reported one or more symptoms of a complex which includes headache, weakness, dizziness, syncope, flushing, tingling, lacrimation, sweating, tightness of face and neck, burning or pressure in the chest often radiating to the neck and arms, heartburn, and gastric distress (Sweetman, 2003; Yang et al, 1997; Goldberg, 1982).

Immunologic

    3.19.2) CLINICAL EFFECTS
    A) ACUTE ALLERGIC REACTION
    1) WITH POISONING/EXPOSURE
    a) Although allergic reactions have been reported in several individuals taking MSG in case reports, no evidence for an immune allergic mechanisms (eg; MSG-specific IgE) could be found (Pulce et al, 1992).
    b) Although, in one study, oral challenge with MSG produced symptoms in MSG-sensitive patients, no patient had the development of rhinoconjunctivitis, asthma, urticaria, angioedema, or anaphylactoid reaction. This suggests that conventional allergic mechanisms (eg; IgE and mast cells) probably do not play a role in the MSG symptom complex or Chinese Restaurant Syndrome (Yang et al, 1997).
    B) OROFACIAL GRANULOMATOSIS
    1) WITH POISONING/EXPOSURE
    a) CASE REPORT: MSG-induced orofacial granulomatosis has been reported in a 15-year-old female. A radioallergosorbent test (RAST) was performed and a positive response to a commercially available tomato paste (with MSG) was observed. After starting a MSG-free diet, an improvement in the facial swelling was noted (Oliver et al, 1991).

Reproductive

    3.20.1) SUMMARY
    A) In animal studies, MSG was not teratogenic. Glutamate crosses the placental barrier at a rate slower than that of simple diffusion; however, due to rapid metabolism of glutamate to glucose and lactate within the placenta, fetal glutamate plasma concentrations are much lower than maternal glutamate plasma concentrations.
    3.20.2) TERATOGENICITY
    A) LACK OF EFFECT
    1) In animal studies, MSG was not teratogenic (Pulce et al, 1992).
    3.20.3) EFFECTS IN PREGNANCY
    A) PLACENTAL BARRIER
    1) Glutamate crosses the placental barrier at a rate slower than that of simple diffusion; however, due to rapid metabolism of glutamate to glucose and lactate within the placenta, fetal glutamate plasma concentrations are much lower than maternal glutamate plasma concentrations (Pulce et al, 1992).

Carcinogenicity

    3.21.1) IARC CATEGORY
    A) IARC Carcinogenicity Ratings for CAS142-47-2 (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
    3.21.4) ANIMAL STUDIES
    A) LACK OF EFFECT
    1) In animal studies, there was no evidence for MSG-associated carcinogenicity (Pulce et al, 1992).

Laboratory Monitoring

Monitoring Parameters Levels

    4.1.1) SUMMARY
    A) No specific laboratory tests are necessary unless otherwise clinically indicated.
    B) Plasma concentrations are not readily available or clinically useful in the management of overdose.
    C) Monitor vital signs and mental status in symptomatic patients.
    D) Monitor serum electrolytes in patients with significant vomiting and/or diarrhea.

Treatment

Life Support

    A) Support respiratory and cardiovascular function.

Patient Disposition

    6.3.1) DISPOSITION/ORAL EXPOSURE
    6.3.1.1) ADMISSION CRITERIA/ORAL
    A) Patients with severe symptoms despite treatment should be admitted.
    6.3.1.2) HOME CRITERIA/ORAL
    A) A patient with an inadvertent exposure, that remains asymptomatic can be managed at home.
    6.3.1.3) CONSULT CRITERIA/ORAL
    A) Consult a regional poison center or medical toxicologist for assistance in managing patients with severe toxicity or in whom the diagnosis is not clear.
    6.3.1.5) OBSERVATION CRITERIA/ORAL
    A) Symptomatic patients should be monitored until they are clearly improving and clinically stable.

Monitoring

    A) No specific laboratory tests are necessary unless otherwise clinically indicated.
    B) Plasma concentrations are not readily available or clinically useful in the management of overdose.
    C) Monitor vital signs and mental status in symptomatic patients.
    D) Monitor serum electrolytes in patients with significant vomiting and/or diarrhea.

Oral Exposure

    6.5.1) PREVENTION OF ABSORPTION/PREHOSPITAL
    A) Gastrointestinal decontamination is generally not indicated after an acute ingestion. Toxicity is very unlikely.
    6.5.2) PREVENTION OF ABSORPTION
    A) Gastrointestinal decontamination is generally not indicated after an acute ingestion. Toxicity is very unlikely.
    6.5.3) TREATMENT
    A) SUPPORT
    1) MANAGEMENT OF TOXICITY
    a) Treatment is symptomatic and supportive. Toxicity is very unlikely. Correct any significant fluid and/or electrolyte abnormalities in patients with severe diarrhea and/or vomiting. In patients with acute allergic reaction, oxygen therapy, bronchodilators, diphenhydramine, corticosteroids, vasopressors and epinephrine may be required.
    B) MONITORING OF PATIENT
    1) No specific laboratory tests are necessary unless otherwise clinically indicated.
    2) Plasma concentrations are not readily available or clinically useful in the management of overdose.
    3) Monitor vital signs and mental status in symptomatic patients.
    4) Monitor serum electrolytes in patients with significant vomiting and/or diarrhea.
    C) HYPERSENSITIVITY REACTION
    1) SUMMARY
    a) Mild to moderate allergic reactions may be treated with antihistamines with or without inhaled beta adrenergic agonists, corticosteroids or epinephrine. Treatment of severe anaphylaxis also includes oxygen supplementation, aggressive airway management, epinephrine, ECG monitoring, and IV fluids.
    2) BRONCHOSPASM
    a) ALBUTEROL
    1) ADULT: 2.5 to 5 milligrams in 2 to 4.5 milliliters of normal saline delivered per nebulizer every 20 minutes up to 3 doses. If incomplete response administer 2.5 to 10 mg every 1 to 4 hours as needed, or 10 to 15 mg/hr by continuous nebulization as needed (National Heart,Lung,and Blood Institute, 2007). CHILD: 0.15 milligram/kilogram (minimum 2.5 milligrams) per nebulizer every 20 minutes up to 3 doses. If incomplete response administer 0.15 to 0.3 mg/kg (up to 10 mg) every 1 to 4 hours as needed, or 0.5 mg/kg/hr by continuous nebulization (National Heart,Lung,and Blood Institute, 2007).
    3) CORTICOSTEROIDS
    a) Consider systemic corticosteroids in patients with significant bronchospasm.
    b) PREDNISONE: ADULT: 40 to 80 milligrams/day. CHILD: 1 to 2 milligrams/kilogram/day (maximum 60 mg) in 1 to 2 divided doses divided twice daily (National Heart,Lung,and Blood Institute, 2007).
    4) MILD CASES
    a) DIPHENHYDRAMINE
    1) SUMMARY: Oral diphenhydramine, as well as other H1 antihistamines can be used as indicated (Lieberman et al, 2010).
    2) ADULT: 50 milligrams orally, or 10 to 50 mg intravenously at a rate not to exceed 25 mg/min or may be given by deep intramuscular injection. A total of 100 mg may be administered if needed. Maximum daily dosage is 400 mg (Prod Info diphenhydramine HCl intravenous injection solution, intramuscular injection solution, 2013).
    3) CHILD: 5 mg/kg/24 hours or 150 mg/m(2)/24 hours. Divided into 4 doses, administered intravenously at a rate not exceeding 25 mg/min or by deep intramuscular injection. Maximum daily dosage is 300 mg (Prod Info diphenhydramine HCl intravenous injection solution, intramuscular injection solution, 2013).
    5) MODERATE CASES
    a) EPINEPHRINE: INJECTABLE SOLUTION: It should be administered early in patients by IM injection. Using a 1:1000 (1 mg/mL) solution of epinephrine. Initial Dose: 0.01 mg/kg intramuscularly with a maximum dose of 0.5 mg in adults and 0.3 mg in children. The dose may be repeated every 5 to 15 minutes, if no clinical improvement. Most patients respond to 1 or 2 doses (Nowak & Macias, 2014).
    6) SEVERE CASES
    a) EPINEPHRINE
    1) INTRAVENOUS BOLUS: ADULT: 1 mg intravenously as a 1:10,000 (0.1 mg/mL) solution; CHILD: 0.01 mL/kg intravenously to a maximum single dose of 1 mg given as a 1:10,000 (0.1 mg/mL) solution. It can be repeated every 3 to 5 minutes as needed. The dose can also be given by the intraosseous route if IV access cannot be established (Lieberman et al, 2015). ALTERNATIVE ROUTE: ENDOTRACHEAL ADMINISTRATION: If IV/IO access is unavailable. DOSE: ADULT: Administer 2 to 2.5 mg of 1:1000 (1 mg/mL) solution diluted in 5 to 10 mL of sterile water via endotracheal tube. CHILD: DOSE: 0.1 mg/kg to a maximum of 2.5 mg administered as a 1:1000 (1 mg/mL) solution diluted in 5 to 10 mL of sterile water via endotracheal tube (Lieberman et al, 2015).
    2) INTRAVENOUS INFUSION: Intravenous administration may be considered in patients poorly responsive to IM or SubQ epinephrine. An epinephrine infusion may be prepared by adding 1 mg (1 mL of 1:1000 (1 mg/mL) solution) to 250 mL D5W, yielding a concentration of 4 mcg/mL, and infuse this solution IV at a rate of 1 mcg/min to 10 mcg/min (maximum rate). CHILD: A dosage of 0.01 mg/kg (0.1 mL/kg of a 1:10,000 (0.1 mg/mL) solution up to 10 mcg/min (maximum dose 0.3 mg) is recommended for children (Lieberman et al, 2010). Careful titration of a continuous infusion of IV epinephrine, based on the severity of the reaction, along with a crystalloid infusion can be considered in the treatment of anaphylactic shock. It appears to be a reasonable alternative to IV boluses, if the patient is not in cardiac arrest (Vanden Hoek,TL,et al).
    7) AIRWAY MANAGEMENT
    a) OXYGEN: 5 to 10 liters/minute via high flow mask.
    b) INTUBATION: Perform early if any stridor or signs of airway obstruction.
    c) CRICOTHYROTOMY: Use if unable to intubate with complete airway obstruction (Vanden Hoek,TL,et al).
    d) BRONCHODILATORS are recommended for mild to severe bronchospasm.
    e) ALBUTEROL: ADULT: 2.5 to 5 milligrams in 2 to 4.5 milliliters of normal saline delivered per nebulizer every 20 minutes up to 3 doses. If incomplete response administer 2.5 to 10 mg every 1 to 4 hours as needed, or 10 to 15 mg/hr by continuous nebulization as needed (National Heart,Lung,and Blood Institute, 2007).
    f) ALBUTEROL: CHILD: 0.15 milligram/kilogram (minimum 2.5 milligrams) per nebulizer every 20 minutes up to 3 doses. If incomplete response administer 0.15 to 0.3 milligram/kilogram (maximum 10 milligrams) every 1 to 4 hours as needed OR administer 0.5 mg/kg/hr by continuous nebulization (National Heart,Lung,and Blood Institute, 2007).
    8) MONITORING
    a) CARDIAC MONITOR: All complicated cases.
    b) IV ACCESS: Routine in all complicated cases.
    9) HYPOTENSION
    a) If hypotensive give 500 to 2000 milliliters crystalloid initially (20 milliliters/kilogram in children) and titrate to desired effect (stabilization of vital signs, mentation, urine output); adults may require up to 6 to 10 L/24 hours. Central venous or pulmonary artery pressure monitoring is recommended in patients with persistent hypotension.
    1) VASOPRESSORS: Should be used in refractory cases unresponsive to repeated doses of epinephrine and after vigorous intravenous crystalloid rehydration (Lieberman et al, 2010).
    2) DOPAMINE: Initial Dose: 2 to 20 micrograms/kilogram/minute intravenously; titrate to maintain systolic blood pressure greater than 90 mm Hg (Lieberman et al, 2010).
    10) H1 and H2 ANTIHISTAMINES
    a) SUMMARY: Antihistamines are second-line therapy and are used as supportive therapy and should not be used in place of epinephrine (Lieberman et al, 2010).
    1) DIPHENHYDRAMINE: ADULT: 25 to 50 milligrams via a slow intravenous infusion or IM. PEDIATRIC: 1 milligram/kilogram via slow intravenous infusion or IM up to 50 mg in children (Lieberman et al, 2010).
    b) RANITIDINE: ADULT: 1 mg/kg parenterally; CHILD: 12.5 to 50 mg parenterally. If the intravenous route is used, ranitidine should be infused over 10 to 15 minutes or diluted in 5% dextrose to a volume of 20 mL and injected over 5 minutes (Lieberman et al, 2010).
    c) Oral diphenhydramine, as well as other H1 antihistamines, can also be used as indicated (Lieberman et al, 2010).
    11) DYSRHYTHMIAS
    a) Dysrhythmias and cardiac dysfunction may occur primarily or iatrogenically as a result of pharmacologic treatment (epinephrine) (Vanden Hoek,TL,et al). Monitor and correct serum electrolytes, oxygenation and tissue perfusion. Treat with antiarrhythmic agents as indicated.
    12) OTHER THERAPIES
    a) There have been a few reports of patients with anaphylaxis, with or without cardiac arrest, that have responded to vasopressin therapy that did not respond to standard therapy. Although there are no randomized controlled trials, other alternative vasoactive therapies (ie, vasopressin, norepinephrine, methoxamine, and metaraminol) may be considered in patients in cardiac arrest secondary to anaphylaxis that do not respond to epinephrine (Vanden Hoek,TL,et al).

Enhanced Elimination

    A) LACK OF INFORMATION
    1) There is no information regarding the effectiveness of hemodialysis or hemoperfusion for the removal of MSG from plasma.

Range Of Toxicity

Summary

    A) TOXICITY: Flushing, facial pressure, chest pain, headache, and nausea have been reported in patients following the ingestion of food containing MSG. Patients usually experience these symptoms within an hour of eating 3 g or more of MSG on an empty stomach. In one study, very high oral doses of glutamate (147 g/day) given to adult humans as the sole source of nonessential nitrogen for 2 to 6 weeks was tolerated, with no neurological changes. In other studies, doses 60 to 150 mg MSG/kg body weight were also tolerated.

Maximum Tolerated Exposure

    A) Flushing, facial pressure, chest pain, headache, and nausea have been reported in patients following the ingestion of food containing MSG. Patients usually experience these symptoms within an hour of eating 3 g or more of MSG on an empty stomach (Sweetman, 2003).
    B) In one study, very high oral doses of glutamate (147 g/day) given to adult humans as the sole source of nonessential nitrogen for 2 to 6 weeks was tolerated, with no neurological changes (Bazzano et al, 1970). In other studies, doses 60 to 150 mg MSG/kg body weight were also tolerated (Geha et al, 2000).

Serum Plasma Blood Concentrations

    7.5.2) TOXIC CONCENTRATIONS
    A) TOXIC CONCENTRATION LEVELS
    1) Because of the slow absorption of glutamate from the gut and its metabolism within mucosal cells of the intestine and in the liver, low plasma glutamate levels are observed after large quantities of dietary protein. It has been suggested that the amount and the concentration of MSG ingested are important factors in the elevation of plasma glutamate levels (Pulce et al, 1992).

Workplace Standards

    A) ACGIH TLV Values for CAS142-47-2 (American Conference of Governmental Industrial Hygienists, 2010):
    1) Not Listed

    B) NIOSH REL and IDLH Values for CAS142-47-2 (National Institute for Occupational Safety and Health, 2007):
    1) Not Listed

    C) Carcinogenicity Ratings for CAS142-47-2 :
    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 CAS142-47-2 (U.S. Occupational Safety, and Health Administration (OSHA), 2010):
    1) Not Listed

Toxicity Information

    7.7.1) TOXICITY VALUES
    A) LD50- (INTRAPERITONEAL)RAT:
    1) 4253 mg/kg (Behavioral - Convulsions or effect on seizure threshold; Tetany) (RTECS, 2003)
    B) LD50- (ORAL)RAT:
    1) 16600 mg/kg (RTECS, 2003)
    C) LD50- (SUBCUTANEOUS)RAT:
    1) 5580 mg/kg (Behavioral - Tremor; Behavioral - Ataxia; Lung, Thorax, or Respiration - Cyanosis) (RTECS, 2003)
    D) LD50- (INTRAPERITONEAL)MOUSE:
    1) 3800 mg/kg (RTECS, 2003)
    E) LD50- (ORAL)MOUSE:
    1) 11400 mg/kg (RTECS, 2003)
    F) LD50- (SUBCUTANEOUS)MOUSE:
    1) 8200 mg/kg (Behavioral - Convulsions or effect on seizure threshold; Behavioral - Excitement) (RTECS, 2003)

Pharmacology Toxicology

Toxicologic Mechanism

    A) Although several mechanisms have been proposed to explain MSG Symptom Complex or Chinese Restaurant Syndrome (CRS), none have been proven.
    B) HUMAN
    1) Glutamic acid, or glutamate, is a major "building block" of many proteins in foods, such as cheese, meat, pea, mushrooms, and milk. Monosodium glutamate (MSG) is the monosodium salt of L-glutamic acid. Some glutamate is present in foods in a "free" form, not bound with other amino acids. It is only in this free form that glutamate can enhance a food's flavor. Part of the flavor-enhancing effect of tomatoes, certain cheeses, and fermented or hydrolyzed protein products is due to the presence of free glutamate. Hydrolyzed proteins, or protein hydrolysates, are acid-treated or enzymatically-treated proteins from certain food sources. They contain salts of free amino acids, including glutamates, at levels of 5 to 20 percent (Anon, 2003; HSDB, 2003; Anon, 1995).
    2) Many western scientists believe that MSG stimulates taste receptors in the tongue, while their eastern counterparts believe the chemical has a unique fifth basic taste, beyond salty, sweet, sour, and bitter, that they call "umami," derived from the Japanese word meaning "deliciousness" (Anon, 1995; Pulce et al, 1992).
    3) L-glutamate, a prototype of excitatory amino acid neurotransmitter, is used by 15% to 20% of synaptic connections in the CNS (Pulce et al, 1992).
    4) MSG Symptom Complex or Chinese Restaurant Syndrome (CRS) - Although several mechanisms have been proposed, none has been proven. In review articles (Geha et al, 2000; Pulce et al, 1992), some of the following proposed mechanisms are listed:
    a) The stimulation of peripheral receptors may be the mechanism for CRS: In one study, after MSG injection, restriction of circulation by the application of an axillary cuff confined burning sensation to the arm.
    b) CRS was a form of acetylcholinosis: In one study, it was noted that the symptoms of CRS were similar to those observed after acetylcholine use. Glutamate can be converted to acetylcholine via the tricarboxylic acid (TCA) cycle, and drugs affecting the cholinergic mechanisms could modulate CRS symptoms.
    c) CRS may be a manifestation of esophageal irritation.
    d) Chinese meals increase plasma sodium levels, causing CRS.
    e) Vitamin B6 deficiency in individuals may cause CRS.
    1) Glutamic oxaloacetic transaminase of erythrocytes (EGOT) is an important enzyme involved in the metabolism of glutamate. In one study, it was shown that individuals with relatively low basal activities of EGOT, responded to MSG with neurological symptomatology. However, when these patients (n=9) were given vitamin B6, 8 patients showed no symptoms after exposure to MSG. The authors evaluated these results as evidence of a deficiency of vitamin B6 in the tissues of those subjects who responded to MSG, by developing the neurologic symptoms of Chinese Restaurant Syndrome (Ebadi et al, 1982).
    f) CRS may be caused by histamine; In one study, it was found that some Chinese meals could contain levels of histamine close to the toxic threshold established by the FDA for histamine in foods.
    g) The bacterial contamination of boiled and fried rice from Chinese restaurant by Bacillus cereus.
    h) Immuno-allergic reaction (e.g.; anaphylactic reactions) may be considered to be involved in the occurrence of CRS.
    5) PROVOCATION TESTS
    a) Although a few reports described positive results, the majority of provocation tests, using MSG, failed to reproduce symptoms of CRS in patients (with a history of CRS or in healthy individuals) (Pulce et al, 1992).

Physicochemical

Physical Characteristics

    A) White, practically odorless, free-flowing crystals or crystalline powder; sweet-saline taste in large concentrations; no flavor in small quantity; freely soluble in water; sparingly soluble in alcohol (HSDB, 2003; Sweetman, 2003).

Molecular Weight

    A) 187.1 (Sweetman, 2003)

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