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GLUCAGON

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Classification   |    Detailed evidence-based information

Substances Included Synonyms

Therapeutic Toxic Class

    A) Glucagon is a single-chain polypeptide hormone that contains 29 amino acids and is identical to human glucagon. It primarily acts to maintain glucose production through both glycogenolysis and gluconeogenesis, proteolysis in muscle tissue and lipolysis in adipose tissue to increase serum glucose.

Specific Substances

    1) Glucagon
    2) Glucagon hydrochloride
    3) CAS 16941-32-5
    4) Molecular Formula: C(153)H(225)N(43)O(49)S
    1.2.1) MOLECULAR FORMULA
    1) C153H225N43O49S (Prod Info GlucaGen(R) subcutaneous injection, intramuscular injection, intravenous injection, 2015)

Available Forms Sources

    A) FORMS
    1) Glucagon Emergency Kit - Glucagon 1 mg (1 unit) with 1 mL of sterile water for reconstitution in a disposable syringe (Prod Info glucagon injection, 2005; Prod Info GLUCAGEN(R) HYPOKIT injection, 2004).
    B) USES
    1) HYPOGLYCEMIA - Glucagon is used in the treatment of severe hypoglycemia in patients with adequate liver glycogen stores (Prod Info glucagon injection, 2005). Glucagon kits are available for emergency use and contain 1 vial containing 1 mg of glucagon {rDNA origin} for injection with a disposable syringe containing 1 mL of sterile water for reconstitution (Prod Info GLUCAGEN(R) HYPOKIT injection, 2004; Prod Info GLUCAGEN(R) HYPOKIT injection, 2004). It should be administered either by the intramuscular or subcutaneous route to patients that are unconscious or unable to swallow. Once the patient regains consciousness, an oral carbohydrate should be given to prevent secondary hypoglycemia and to partly restore potentially depleted hepatic glycogen stores. If no response to glucagon, seek medical help immediately (Pearson, 2008).
    2) ANTIDOTE (BETA-ADRENERGIC and CALCIUM CHANNEL BLOCKERS) - Glucagon has been used in the treatment of beta blocker and calcium channel blocker overdose (Lee, 2004; Bailey, 2003; Papadopoulos & O'Neil, 2000). It has cardiac inotropic and chronotropic effects. There is also in vitro evidence that glucagon decreases conduction time (Seger, 2006).
    3) In cases of symptomatic bradycardia and hypotension following a beta-blocker overdose, high-dose glucagon is considered first-line antidote therapy (Shepherd, 2006). The clinical effects following a calcium channel blocker overdose can be similar to a beta-adrenergic antagonist overdose, which can include hypotension, bradycardia, heart block, and myocardial depression. Animal studies have shown that glucagon can reverse the myocardial depression that is observed with nifedipine, diltiazem and verapamil toxicity (Howland, 2006).
    a) CALCIUM CHANNEL BLOCKER - A 59-year-old man took a "handful" of 30-mg extended-release tablets and was admitted with hypotension. Despite pharmacologic support, blood pressure ranged from 55/40 to 77/53 mmHg. The patient was given 1 mg of glucagon IV every 3 minutes for a total of 4 doses; blood pressure increased to 127/78 mmHg and the patient became more alert. A glucagon drip was started and maintained for approximately 17 hours when the patient was weaned from norepinephrine. The patient completely recovered (Papadopoulos & O'Neil, 2000).
    4) TRICYCLIC ANTIDEPRESSANTS (TCA) - TCAs, sodium channel blocking agents, can produce cardiotoxicity. In case reports of TCA cardiotoxicity, use of glucagon has been associated with improved hemodynamic function when used in conjunction with multiple other agents. It has been shown that glucagon improves action potential, which suggests that it can increase the movement of sodium ions into the cardiac cell and decrease conduction time (Seger, 2006; Sensky & Olczak, 1999).
    a) CASE REPORT - A 36-year-old woman developed profound hypotension (persistent systolic hypotension of 50-60 mmHg), cardiac dysrhythmias, and seizures following a dothiepin overdose. Although the patient was receiving several inotropic agents, the administration of a 10 mg bolus of glucagon improved blood pressure to 90 mmHg. Several further doses of glucagon were given and the patient recovered fully by day 5. Heart rate was stable after the second dose of glucagon (Sensky & Olczak, 1999). The authors concluded that glucagon significantly contributed to the hemodynamic stabilization and improvement of this patient.
    5) DIAGNOSTIC AID - Parenteral administration of glucagon can relax smooth muscle and diminish intestinal motility, therefore; it is useful in the radiologic examination of the stomach, duodenum, small bowel, and colon (Prod Info glucagon injection, 2005).(Maglinte & Chernish, 1992).
    6) COMATOSE PATIENTS/NOT RECOMMENDED - Glucagon had been recommended in the past as an initial treatment for all comatose patients to treat suspected hypoglycemia; its use is NO longer recommended. Two disadvantages of its use: (1) a patient must have adequate glycogen stores, and (2) it takes time for it to act. Intravenous dextrose (0.5 to 1.0 g/kg of 50% dextrose) is the preferred agent to give to all patients that present with an altered mental status thought to be related to hypoglycemia. Glucagon can have a role in treating hypoglycemia in the home (ie, prepared Glucagon kits) when intravenous dextrose is not available. In patients with insulinoma, glucagon can produce a rebound hypoglycemia following a temporary rise in blood sugar (Howland, 2006).

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: Glucagon is indicated for the treatment of severe hypoglycemia, and to treat beta blocker overdose and less commonly calcium channel blocker overdose. It may also be used as a diagnostic aid and to treat esophageal foreign bodies.
    B) PHARMACOLOGY: Glucagon induces liver glycogen breakdown, releasing glucose from the liver. Hepatic stores of glycogen are needed for glucagon to produce an antihypoglycemic effect. Binding of glucagon to receptors on the heart stimulates conversion of DTP to cyclic AMP, which increases heart rate and strength of contraction.
    C) EPIDEMIOLOGY: Overdose is uncommon.
    D) WITH THERAPEUTIC USE
    1) ADVERSE EFFECTS: Nausea and vomiting may be expected. Severe reactions are not anticipated. Reactive hypoglycemia can develop following the administration of glucagon. Hypokalemia may also occur. Acute allergic reactions (including urticaria, respiratory distress, and hypotension) have been reported rarely following intravenous administration.
    E) WITH POISONING/EXPOSURE
    1) MILD TO MODERATE TOXICITY: Symptoms of nausea, vomiting, gastric hypotonicity and diarrhea would be expected following overdose. Toxicity is anticipated to be an extension of adverse events reported and may include: hyperglycemia or hypoglycemia, hypokalemia, and an increase in blood pressure.
    2) SEVERE TOXICITY: Based on its short half-life, significant protracted overdose effects are not expected to develop.
    0.2.8) GASTROINTESTINAL
    A) WITH THERAPEUTIC USE
    1) Nausea and vomiting are the most common effects with therapeutic use.
    B) WITH POISONING/EXPOSURE
    1) Nausea, vomiting and gastric hypotonicity are anticipated following exposure.
    0.2.12) FLUID-ELECTROLYTE
    A) WITH THERAPEUTIC USE
    1) Hypokalemia is possible with therapeutic use or following exposure.
    0.2.20) REPRODUCTIVE
    A) Glucagon is classified as FDA pregnancy category B. There are no adequate and well-controlled studies of glucagon in pregnant women. Studies in rats and rabbits have shown no harm to the fetus nor impairment of fertility.

Laboratory Monitoring

    A) Assess fluid and electrolyte status in patients with significant nausea and vomiting.
    B) Monitor serial blood glucose following exposure; hyperglycemia or hypoglycemia can develop.
    C) Hypokalemia may occur in overdose.
    D) Monitor vital signs.

Treatment Overview

    0.4.2) ORAL/PARENTERAL EXPOSURE
    A) Treatment is symptomatic and supportive. Refer to the PARENTERAL EXPOSURE section for treatment recommendations following exposure.
    0.4.6) PARENTERAL EXPOSURE
    A) MANAGEMENT OF MILD TO MODERATE TOXICITY
    1) In cases of overdose, treatment is symptomatic and supportive. Rebound hypoglycemia may occur following therapeutic use or acute toxicity of glucagon. Treat significant hypoglycemia with IV dextrose followed by 300 grams daily or more of carbohydrates when the patient is tolerating oral feedings to supplement IV dextrose and prevent secondary hypoglycemia. Nausea, vomiting and a decrease in GI tract motility may develop. Administer IV fluids/electrolytes as indicated. Monitor vital signs for alterations in blood pressure (hypo- or hypertension) and pulse. Monitor serum potassium.
    B) MANAGEMENT OF SEVERE TOXICITY
    1) Severe toxicity is not anticipated in most cases. Glucagon has a short half-life (less than an hour), significant protracted overdose effects are not anticipated. Assess and treat hypoglycemic symptoms. Monitor blood pressure. If severe hypertension develops, phentolamine mesylate has been shown to lower blood pressure for the brief period that control is necessary.
    C) DECONTAMINATION
    1) PREHOSPITAL: Decontamination is not necessary. Glucagon is administered parenterally. Following inadvertent ingestion it is rapidly destroyed in the gastrointestinal tract. Consider activated charcoal only if a mixed ingestion is suspected; protect airway as necessary.
    2) HOSPITAL: Decontamination is not necessary. Glucagon is administered parenterally. Consider activated charcoal only if a mixed ingestion is suspected; protect airway as necessary.
    D) AIRWAY MANAGEMENT
    1) Airway management is unlikely to be necessary.
    E) HYPOGLYCEMIA
    1) Rebound hypoglycemia may occur following therapeutic use or acute toxicity of glucagon. DEXTROSE: If patient symptomatic or has a blood glucose level less than 60 mg/dL administer an IV bolus (50 mL) of 50% dextrose over a period of 2 to 3 minutes. Once the patient is alert they should eat a high carbohydrate meal. Monitor blood glucose; serial readings. In children administer 2 to 4 mL/kg of D25W.
    F) HYPOKALEMIA
    1) Monitor serum potassium. Administer oral or IV potassium chloride as necessary.
    G) PATIENT DISPOSITION
    1) OBSERVATION CRITERIA: Patients should be observed until symptoms resolve and blood glucose is stable. Based on its short half-life, patients can likely be managed in the Emergency Department, and discharged to home once the patient is tolerating oral feedings.
    2) ADMISSION CRITERIA: Patients with persistent alterations in blood glucose or blood pressure may need to be admitted.
    3) CONSULT CRITERIA: Consult with a medical toxicologist or poison center if the clinical symptoms persist or in whom the diagnosis is unclear.
    H) PREDISPOSING CONDITIONS
    1) Patients with a history of having insulinoma may have an exaggerated insulin release following glucagon administration. Glucagon should also be administered with caution in patients with a history of glucagonoma. Adequate glucose stores in the liver (as glycogen) are needed for glucagon to reverse hypoglycemia; therefore glucagon should be used cautiously in patients with prolonged fasting, starvation, adrenal insufficiency or chronic hypoglycemia because these states can result in low levels of glucose release in the liver and produce an inadequate reversal of hypoglycemia by glucagon.
    I) PHARMACOKINETICS
    1) Glucagon induces liver glycogen breakdown, releasing glucose from the liver. Hepatic stores of glycogen are needed for glucagon to produce an antihypoglycemic effect. If given for the treatment of severe hypoglycemia, blood glucose concentration can rise within 10 minutes of injection; maximal concentrations are reached at approximately 30 minutes. The duration of hyperglycemic action after IV or IM injection is 60 to 90 minutes. Apparent half-life after IM injection is 45 minutes and may reflect prolonged absorption from the injection site. Glucagon is degraded in the liver, kidney and plasma.
    J) DIFFERENTIAL DIAGNOSIS
    1) Patients with a history of hypo- or hyperglycemia related to a disease process (ie, diabetes mellitus, adrenal insufficiency). Other agents that produce or potentiate alterations in blood glucose.

Range Of Toxicity

    A) There are no reports of overdose in humans. Intravenous bolus doses of 10 mg have been tolerated in adults receiving glucagon for beta-blocker overdose.

Clinical Effects

Summary Of Exposure

    A) USES: Glucagon is indicated for the treatment of severe hypoglycemia, and to treat beta blocker overdose and less commonly calcium channel blocker overdose. It may also be used as a diagnostic aid and to treat esophageal foreign bodies.
    B) PHARMACOLOGY: Glucagon induces liver glycogen breakdown, releasing glucose from the liver. Hepatic stores of glycogen are needed for glucagon to produce an antihypoglycemic effect. Binding of glucagon to receptors on the heart stimulates conversion of DTP to cyclic AMP, which increases heart rate and strength of contraction.
    C) EPIDEMIOLOGY: Overdose is uncommon.
    D) WITH THERAPEUTIC USE
    1) ADVERSE EFFECTS: Nausea and vomiting may be expected. Severe reactions are not anticipated. Reactive hypoglycemia can develop following the administration of glucagon. Hypokalemia may also occur. Acute allergic reactions (including urticaria, respiratory distress, and hypotension) have been reported rarely following intravenous administration.
    E) WITH POISONING/EXPOSURE
    1) MILD TO MODERATE TOXICITY: Symptoms of nausea, vomiting, gastric hypotonicity and diarrhea would be expected following overdose. Toxicity is anticipated to be an extension of adverse events reported and may include: hyperglycemia or hypoglycemia, hypokalemia, and an increase in blood pressure.
    2) SEVERE TOXICITY: Based on its short half-life, significant protracted overdose effects are not expected to develop.

Cardiovascular

    3.5.2) CLINICAL EFFECTS
    A) FINDING OF INCREASED BLOOD PRESSURE
    1) WITH THERAPEUTIC USE
    a) An increase in blood pressure can occur in patients with coronary artery disease or pheochromocytoma (Prod Info GlucaGen(R) intravenous intramuscular subcutaneous injection, 2010).
    b) HIGH-DOSE THERAPY: Intravenous glucagon administration can produce a dose-dependent positive inotropic and chronotropic effects. Transient increases in blood pressure and pulse rate may occur with glucagon administration (Prod Info GlucaGen(R) intravenous intramuscular subcutaneous injection, 2010; Sensky & Olczak, 1999).
    B) HYPERTENSIVE CRISIS
    1) WITH THERAPEUTIC USE
    a) In select patients, hypertensive crisis can develop in patients with pheochromocytoma, due to the release of catecholamines following glucagon administration (Prod Info GlucaGen(R) intravenous intramuscular subcutaneous injection, 2010; Howland, 2006).
    C) TACHYCARDIA
    1) WITH THERAPEUTIC USE
    a) An increase in heart rate has been reported with the therapeutic use of glucagon (Prod Info GlucaGen(R) intravenous intramuscular subcutaneous injection, 2010; Bailey, 2003; Hashimoto et al, 2002).
    b) DIAGNOSTIC USE: In a prospective, randomized, multicenter study of 240 patients referred for an upper gastrointestinal endoscopy, transient increases in heart rate of 10 beats/min above baseline were observed, but gradually declined by the end of the procedure in patients receiving glucagon (Hashimoto et al, 2002).
    D) VASOSPASM
    1) WITH THERAPEUTIC USE
    a) Hepatic Artery Vasospasm
    1) DIAGNOSTIC STUDY: A 69-year-old man with a history of vasculitis with possible renal and mesenteric involvement underwent digital subtraction angiography and received a contrast agent, as well as 1 mg of glucagon IV to slow bowel motility. Vasospasm of the hepatic artery branches were noted during visceral angiography; the event was noted to be transient, but reproducible with a repeat injection of glucagon (Dziedzic & Smith, 2007). The authors were unable to determine the exact cause for this response.

Gastrointestinal

    3.8.1) SUMMARY
    A) WITH THERAPEUTIC USE
    1) Nausea and vomiting are the most common effects with therapeutic use.
    B) WITH POISONING/EXPOSURE
    1) Nausea, vomiting and gastric hypotonicity are anticipated following exposure.
    3.8.2) CLINICAL EFFECTS
    A) NAUSEA AND VOMITING
    1) WITH THERAPEUTIC USE
    a) Nausea is the most common event reported with therapy; vomiting may also develop (Prod Info GlucaGen(R) intravenous intramuscular subcutaneous injection, 2010; Chernish & Maglinte, 1990).
    b) An investigation of the mechanism for glucagon-induced nausea suggests that the reaction is not mediated by effects on the brain, but rather due to the delay in gastric emptying caused by glucagon. Delayed gastric emptying may inhibit the proximal small intestine and prevent transport and assimilation of nutrients, leading to nausea and vomiting (Ranganath et al, 1999).

Hepatic

    3.9.2) CLINICAL EFFECTS
    A) VASOSPASM
    1) WITH THERAPEUTIC USE
    a) Hepatic Artery Vasospasm
    1) DIAGNOSTIC STUDY: A 69-year-old man with a history of vasculitis with possible renal and mesenteric involvement underwent digital subtraction angiography and received a contrast agent, as well as 1 mg of glucagon IV to slow bowel motility. Vasospasm of the hepatic artery branches were noted during visceral angiography; the event was noted to be transient, but reproducible with a repeat injection of glucagon (Dziedzic & Smith, 2007). The authors were unable to determine the exact cause for this response.

Endocrine

    3.16.2) CLINICAL EFFECTS
    A) HYPERGLYCEMIA
    1) WITH THERAPEUTIC USE
    a) Hyperglycemia can potentially occur with high-dose therapy or a continuous glucagon infusion (Papadopoulos & O'Neil, 2000).
    b) CASE REPORT: Hyperglycemia was the only adverse event reported in an adult following a severe nifedipine overdose. The patient received a glucagon infusion for hemodynamic stability for approximately 17 hours. The patient recovered uneventfully (Papadopoulos & O'Neil, 2000).
    B) HYPOGLYCEMIA
    1) WITH THERAPEUTIC USE
    a) Hypoglycemia can develop with glucagon administration and may be dose-dependent (Prod Info GlucaGen(R) intravenous intramuscular subcutaneous injection, 2010; Howland, 2006). Reactive hypoglycemia can occur as a response to glucagon-induced hyperglycemia, which stimulates insulin release (DeWitt & Waksman, 2004a; Hashimoto et al, 2002; White, 1999; Thoma et al, 1996).
    b) DIAGNOSTIC USE: In a prospective, randomized, multicenter study of 240 patients referred for an upper gastrointestinal endoscopy, mild to severe hypoglycemia occurred in 15 (25%) and 5 (8.3%) patients treated with glucagon, as compared to 9 (15%) and 1 (1.7%), patients receiving butyl scopolamine, respectively. The administration of glucose tablets (given approximately 60 minutes after the procedure) also significantly reduced the incidence of hypoglycemia in the glucagon group (Hashimoto et al, 2002).

Immunologic

    3.19.2) CLINICAL EFFECTS
    A) HYPERSENSITIVITY REACTION
    1) WITH THERAPEUTIC USE
    a) There have been infrequent reports of allergic reactions, including urticaria, respiratory distress, and hypotension, following parenteral administration of glucagon (Prod Info GlucaGen(R) intravenous intramuscular subcutaneous injection, 2010).
    b) CASE REPORT: A 41-year-old man with a history of asthma experienced a severe allergic reaction to glucagon administered prior to contrast barium abdominal examination. Within two minutes of receiving 1 mg of IV glucagon, the patient became dizzy and short of breath. Despite treatment with oxygen, subcutaneous adrenaline, intravenous steroids, and hydration, symptoms progressed to include shaking and chills. Contrast medium was never administered, and with further treatment, the patient slowly improved (Herskovitz & Sendovski, 1997).

Reproductive

    3.20.1) SUMMARY
    A) Glucagon is classified as FDA pregnancy category B. There are no adequate and well-controlled studies of glucagon in pregnant women. Studies in rats and rabbits have shown no harm to the fetus nor impairment of fertility.
    3.20.2) TERATOGENICITY
    A) ANIMAL STUDIES
    1) GLUCAGON
    a) RATS: No harm to the fetus was found when rats were administered animal-sourced glucagon doses up to 40 times the human dose based on a mg/m(2) basis (Prod Info glucagon rDNA origin intravenous injection, intramuscular injection, subcutaneous injection, 2012).
    2) GLUCAGON HYDROCHLORIDE
    a) RABBITS: No harm to the fetus was found rabbits were administered glucagon hydrochloride doses up to 200 times the human dose based on mg/m(2) (Prod Info GlucaGen(R) intramuscular injection, intravenous injection, subcutaneous injection, 2014).
    b) RATS: No harm to the fetus was found rats were administered glucagon hydrochloride doses up to 100 times the human dose based on mg/m(2) (Prod Info GlucaGen(R) intramuscular injection, intravenous injection, subcutaneous injection, 2014).
    3.20.3) EFFECTS IN PREGNANCY
    A) PREGNANCY CATEGORY
    1) Glucagon and glucagon hydrochloride are classified by the manufacturer as FDA pregnancy category B (Prod Info GlucaGen(R) intramuscular injection, intravenous injection, subcutaneous injection, 2014; Prod Info glucagon rDNA origin intravenous injection, intramuscular injection, subcutaneous injection, 2012).
    B) LACK OF EFFECT
    1) GLUCAGON
    a) The data are limited in treating pregnant women with glucagon. Data has shown that infants born to 16 women who received glucagon for treating hypoglycemia during pregnancy had no major malformations at birth (Rayburn et al, 1987). Until additional data are available, caution should be exercised with glucagon use in a pregnant woman.
    3.20.4) EFFECTS DURING BREAST-FEEDING
    A) BREAST MILK
    1) GLUCAGON: It is unknown if glucagon is excreted in human breast milk; however, as glucagon is a peptide and intact glucagon is not absorbed from the gastrointestinal tract, it is unlikely to cause harm to an exposed infant. Additionally, any exposure to the infant would likely be limited given glucagon's short plasma half-life (Prod Info GlucaGen(R) intramuscular injection, intravenous injection, subcutaneous injection, 2014; Prod Info glucagon rDNA origin intravenous injection, intramuscular injection, subcutaneous injection, 2012).
    3.20.5) FERTILITY
    A) ANIMAL STUDIES
    1) GLUCAGON
    a) RATS: No evidence of impaired fertility was found when rats were administered animal-sourced glucagon doses up to 40 times the human dose based on a mg/m(2) basis (Prod Info glucagon rDNA origin intravenous injection, intramuscular injection, subcutaneous injection, 2012).
    2) GLUCAGON HYDROCHLORIDE
    a) RATS: Glucagon hydrochloride has not been tested in animal fertility studies. However, studies in rats do not suggest that pancreatic glucagon causes impaired fertility (Prod Info GlucaGen(R) intramuscular injection, intravenous injection, subcutaneous injection, 2014).

Carcinogenicity

    3.21.1) IARC CATEGORY
    A) IARC Carcinogenicity Ratings for CAS16941-32-5 (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

Laboratory Monitoring

Monitoring Parameters Levels

    4.1.1) SUMMARY
    A) Assess fluid and electrolyte status in patients with significant nausea and vomiting.
    B) Monitor serial blood glucose following exposure; hyperglycemia or hypoglycemia can develop.
    C) Hypokalemia may occur in overdose.
    D) Monitor vital signs.

Treatment

Life Support

    A) Support respiratory and cardiovascular function.

Patient Disposition

    6.3.1) DISPOSITION/ORAL EXPOSURE
    6.3.1.1) ADMISSION CRITERIA/ORAL
    A) Patients with persistent alterations in blood glucose or blood pressure may need to be admitted.
    6.3.1.3) CONSULT CRITERIA/ORAL
    A) Consult with a medical toxicologist or poison center if the clinical symptoms persist or in whom the diagnosis is unclear.
    6.3.1.5) OBSERVATION CRITERIA/ORAL
    A) Patients should be observed until symptoms resolve and blood glucose is stable. Based on its short half-life, patients can likely be managed in the Emergency Department, and discharged to home once the patient is tolerating oral feedings.

Monitoring

    A) Assess fluid and electrolyte status in patients with significant nausea and vomiting.
    B) Monitor serial blood glucose following exposure; hyperglycemia or hypoglycemia can develop.
    C) Hypokalemia may occur in overdose.
    D) Monitor vital signs.

Oral Exposure

    6.5.1) PREVENTION OF ABSORPTION/PREHOSPITAL
    A) Decontamination is not necessary. Glucagon is administered parenterally, and can be a potent emetic. Following inadvertent ingestion, decontamination is not indicated because glucagon, a polypeptide, is rapidly destroyed in the gastrointestinal tract.
    B) Consider activated charcoal only if a mixed ingestion is suspected; protect airway as necessary.
    6.5.2) PREVENTION OF ABSORPTION
    A) Following inadvertent oral ingestion, decontamination is not necessary because glucagon, a polypeptide, is rapidly destroyed in the gastrointestinal tract (Prod Info glucagon injection, 2005).
    6.5.3) TREATMENT
    A) SUPPORT
    1) In cases of glucagon overdose, treatment should be symptomatic and supportive.
    B) MONITORING OF PATIENT
    1) Monitor blood glucose and serum electrolytes. Monitor fluid status in patients with severe vomiting. Replace electrolytes and fluids as indicated.
    2) In a patient with persistent vomiting, assess patient's ability to protect airway.
    3) Assess bowel function; gastric hypotonicity is possible following acute exposure.
    C) HYPOGLYCEMIA
    1) Rebound hypoglycemia may occur following therapeutic use or acute toxicity of glucagon. Monitor blood glucose; serial readings may be indicated.
    2) GLUCOSE: If a patient is symptomatic or has a blood glucose level less than 60 mg/dL administer an IV bolus (50 mL) of 50% dextrose over a period of 2 to 3 minutes. Improvement will usually be seen in less than 5 minutes. In children administer 2 to 4 ml/kg of 25% dextrose.
    a) Monitor blood glucose levels regularly to maintain a blood glucose level of 100 mg/dL.
    3) CARBOHYDRATES: Administer 300 grams daily or more of carbohydrates when the patient awakens to supplement IV dextrose and prevent secondary hypoglycemia.
    D) HYPOKALEMIA
    1) Monitor serum potassium.
    2) Administer oral or intravenous potassium chloride to correct hypokalemia.

Enhanced Elimination

    A) LACK OF EFFECT
    1) It is not anticipated that forced diuresis, peritoneal dialysis, hemodialysis, or charcoal hemoperfusion would be beneficial following a glucagon exposure (Prod Info glucagon injection, 2005). Based on its short half-life, these interventions are not indicated.

Range Of Toxicity

Summary

    A) There are no reports of overdose in humans. Intravenous bolus doses of 10 mg have been tolerated in adults receiving glucagon for beta-blocker overdose.

Therapeutic Dose

    7.2.1) ADULT
    A) SEVERE HYPOGLYCEMIA
    1) For adults weighing more than 25 kg, give 1 mg by subQ, IM or IV injection (Prod Info GlucaGen(R) subcutaneous injection, intramuscular injection, intravenous injection, 2013).
    B) DIAGNOSTIC IMAGING
    1) STOMACH, DUODENAL BULB, DUODENUM, AND SMALL BOWEL: 0.2 to 0.5 mg given by IV injection or 1 mg given by IM injection (Prod Info GlucaGen(R) subcutaneous injection, intramuscular injection, intravenous injection, 2013)
    2) COLON: 0.5 to 0.75 mg IV injection and 1 to 2 mg IM injection (Prod Info GlucaGen(R) subcutaneous injection, intramuscular injection, intravenous injection, 2013)
    C) ANTIDOTE FOR CARDIAC TOXICITY
    1) BETA-BLOCKER TOXICITY: Antidotal therapy for beta-blocker overdose is based on animal studies and cases reported in the literature. Glucagon is usually considered the first-line therapy in this setting. However, glucagon is used in conjunction with other agents in most patients. High dose therapy is recommended (Shepherd, 2006).
    2) CALCIUM CHANNEL BLOCKER (CCB): Glucagon improves the myocardial depression observed with these agents (eg, verapamil, nifedipine and diltiazem). Some authors suggest that glucagon should be combined with amrinone (inamrinone) (Howland, 2006), while other suggest that high-dose insulin may be a more promising antidote to CCB toxicity (Shepherd, 2006).
    3) DOSING: An initial intravenous bolus dose of 50 mcg/kg over 1 to 2 minutes is recommended (3 to 5 mg in a 70 kg person); up to 10 mg may be used in adults if the initial bolus dose is ineffective. Following the initial bolus, if an improvement is observed start a continuous INFUSION of 2 to 5 mg/hour (maximum 10 mg/hr) in 5% dextrose in water. The infusion can be slowly weaned as the patient improves. NOTE: This dosing regimen is based on case reports only (Howland, 2006; Shepherd, 2006).
    a) There is experimental evidence that tachyphylaxis can occur with a continuous glucagon administration. It is unclear if this occurs in humans. Desensitization may also develop with continued dosing (Howland, 2006).
    7.2.2) PEDIATRIC
    A) HYPOGLYCEMIA
    1) CHILD WEIGHING LESS THAN 25 KG OR LESS THAN 6 YEARS OF AGE: 0.5 mg (0.5 mL) subQ, IM or IV push (Prod Info GlucaGen(R) subcutaneous injection, intramuscular injection, intravenous injection, 2013)
    2) CHILD WEIGHING GREATER THAN 25 KG OR GREATER THAN 6 YEARS OF AGE: 1 mg (1 mL) subQ, IM or IV push (Prod Info GlucaGen(R) subcutaneous injection, intramuscular injection, intravenous injection, 2013)
    B) GLUCAGON STIMULATION TEST
    1) 0.03 mg/kg IM; maximum 1 mg/dose (di Iorgi et al, 2010; Secco et al, 2009) or 0.1 mg/kg IM; maximum 1 mg/dose (Strich et al, 2009).

Minimum Lethal Exposure

    A) A minimum lethal dose in humans has not been established.
    B) ANIMAL DATA: In mice and rats, the median lethal intravenous dose is approximately 300 mg/kg and 38.6 mg/kg, respectively (Prod Info glucagon injection, 2005).

Maximum Tolerated Exposure

    A) A maximum tolerated dose in humans has not been established.
    B) ANTIDOTE FOR CARDIAC TOXICITY: Glucagon is a first-line antidotal therapy for beta-blocker overdose (Shepherd, 2006). An initial bolus of 50 to 150 mcg/kg (usually about 10 mg in an adult) over 1 minute; followed by a continuous IV infusion of 50 to 100 mcg/kg/hr (DeWitt & Waksman, 2004).

Workplace Standards

    A) ACGIH TLV Values for CAS16941-32-5 (American Conference of Governmental Industrial Hygienists, 2010):
    1) Not Listed

    B) NIOSH REL and IDLH Values for CAS16941-32-5 (National Institute for Occupational Safety and Health, 2007):
    1) Not Listed

    C) Carcinogenicity Ratings for CAS16941-32-5 :
    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 CAS16941-32-5 (U.S. Occupational Safety, and Health Administration (OSHA), 2010):
    1) Not Listed

Pharmacology Toxicology

Pharmacologic Mechanism

    A) Glucagon, a polypeptide hormone similar to human glucagon, increases blood glucose concentration and relaxes the gastrointestinal tract smooth muscles. It converts liver glycogen into glucose and is used in the treatment of hypoglycemia (Prod Info glucagon injection powder for solution, 2005).

Toxicologic Mechanism

    A) Glucagon administration can result in hyperglycemia and rebound hypoglycemia. The increase in blood sugar can result in an immediate increase in insulin secretion, which can result in an intracellular shift in potassium resulting in hypokalemia (Howland, 2006). Following exposure, alterations in blood sugar and possibly hypokalemia should be anticipated, along with nausea and vomiting. Airway management and protection may be indicated in these patients.

Physicochemical

Physical Characteristics

    A) GlucaGen is a sterile lyophilized white powder that is soluble in water (Prod Info GlucaGen(R) subcutaneous injection, intramuscular injection, intravenous injection, 2015).

Ph

    A) 2.5 to 3.5 (Prod Info GlucaGen(R) subcutaneous injection, intramuscular injection, intravenous injection, 2015)

Molecular Weight

    A) 3483 (Prod Info GlucaGen(R) subcutaneous injection, intramuscular injection, intravenous injection, 2015)

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) 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.
    14) Bailey B: Glucagon in beta-blocker and calcium channel blocker overdoses: a systematic review. J Toxicol Clin Toxicol 2003; 41(5):595-602.
    15) Chernish & Maglinte: Glucagon: common untoward reactions-review and recommendations. Radiology 1990; 177, Issue 1:145-6.
    16) 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.
    17) DeWitt CR & Waksman JC: Pharmacology, pathophysiology and management of calcium channel blocker and beta-blocker toxicity. Toxicol Rev 2004; 23:223-238.
    18) DeWitt CR & Waksman JC: Pharmacology, pathophysiology and management of calcium channel blocker and beta-blocker toxicity. Toxicol Rev 2004a; 23(4):223-238.
    19) Dziedzic TS & Smith TP: Glucagon-induced vasospasm of hepatic artery branches during visceral angiography. Cardiovasc Intervent Radiol 2007; Epub:--.
    20) 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/.
    21) Hashimoto T, Adachi K, Ishimura N, et al: Safety and efficacy of glucagon as a premedication for upper gastrointestinal endoscopy--a comparative study with butyl scopolamine bromide. Aliment Pharmacol Ther 2002; 16(1):111-118.
    22) Herskovitz PI & Sendovski U: Severe allergic reaction to intravenous injection of glucagon. Radiology 1997; 202:879.
    23) Howland MA: Antidotes in Depth. In: Goldfrank LR, Flomenbaum N, Hoffman RS, et al, eds. Goldfrank's Toxicologic Emergencies. 8th ed., 8th ed. McGraw-Hill, New York, NY, 2006, pp 826-828.
    24) 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.
    25) 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.
    26) 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.
    27) 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.
    28) 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.
    29) 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.
    30) 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.
    31) 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.
    32) Lee J: Glucagon use in symptomatic beta blocker overdose. Emerg Med J 2004; 21(6):755-755.
    33) Maglinte DD & Chernish SM: The optimal dose of glucagon: what is enough. Radiology 1992; 183(2):326-327.
    34) NFPA: Fire Protection Guide to Hazardous Materials, 13th ed., National Fire Protection Association, Quincy, MA, 2002.
    35) 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.
    36) 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.
    37) 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.
    38) 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.
    39) 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.
    40) 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.
    41) 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.
    42) 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.
    43) 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.
    44) 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.
    45) 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.
    46) 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.
    47) 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.
    48) 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.
    49) 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.
    50) 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.
    51) 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.
    52) 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.
    53) 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.
    54) 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.
    55) 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.
    56) 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.
    57) 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.
    58) 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.
    59) 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.
    60) 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.
    61) 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.
    62) 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.
    63) 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.
    64) 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.
    65) 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.
    66) 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.
    67) 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.
    68) 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.
    69) 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.
    70) 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.
    71) 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.
    72) 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.
    73) 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.
    74) 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.
    75) 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.
    76) 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.
    77) 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.
    78) 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.
    79) 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.
    80) 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.
    81) 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.
    82) 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.
    83) 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.
    84) 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.
    85) 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.
    86) 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.
    87) 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.
    88) 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.
    89) 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.
    90) 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.
    91) 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.
    92) 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.
    93) 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.
    94) 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.
    95) 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.
    96) 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.
    97) 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.
    98) 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.
    99) 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.
    100) 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.
    101) 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.
    102) 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.
    103) 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.
    104) 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.
    105) 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.
    106) 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.
    107) 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.
    108) 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.
    109) 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.
    110) 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.
    111) 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.
    112) 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.
    113) 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.
    114) National Research Council : Acute exposure guideline levels for selected airborne chemicals, 5, National Academies Press, Washington, DC, 2007.
    115) National Research Council: Acute exposure guideline levels for selected airborne chemicals, 6, National Academies Press, Washington, DC, 2008.
    116) National Research Council: Acute exposure guideline levels for selected airborne chemicals, 7, National Academies Press, Washington, DC, 2009.
    117) National Research Council: Acute exposure guideline levels for selected airborne chemicals, 8, National Academies Press, Washington, DC, 2010.
    118) Papadopoulos J & O'Neil MG: Utilization of a glucagon infusion in the management of a massive nifedipine overdose. J Emerg Med 2000; 18(4):453-455.
    119) Pearson T: Glucagon as a treatment of severe hypoglycemia: safe and efficacious but underutilized. Diabetes Educ 2008; 34(1):128-134.
    120) Pontiroli AE, Calderara A, Perfetti MG, et al: Pharmacokinetics of intranasal, intramuscular and intravenous glucagon in healthy subjects and diabetic patients. Eur J Clin Pharmacol 1993; 45:555-558.
    121) Product Information: GLUCAGEN(R) HYPOKIT injection, glucagon [rDNA origin] injection. Novo Nordisk,Inc, Princeton, NJ, 2004.
    122) Product Information: GlucaGen(R) intramuscular injection, intravenous injection, subcutaneous injection, glucagon rDNA origin intramuscular injection, intravenous injection, subcutaneous injection. Boehringer Ingelheim Pharmaceuticals, Inc. (per DailyMed), Ridgefield, CT, 2014.
    123) Product Information: GlucaGen(R) intravenous intramuscular subcutaneous injection, glucagon rDNA origin intravenous intramuscular subcutaneous injection. Novo Nordisk Inc., Princeton, NJ, 2010.
    124) Product Information: GlucaGen(R) subcutaneous injection, intramuscular injection, intravenous injection, glucagon rDNA origin subcutaneous injection, intramuscular injection, intravenous injection. Bedford Laboratories (per DailyMed), Bedford, OH, 2013.
    125) Product Information: GlucaGen(R) subcutaneous injection, intramuscular injection, intravenous injection, glucagon rDNA origin subcutaneous injection, intramuscular injection, intravenous injection. Novo Nordisk Inc. (per FDA), Plainsboro, NJ, 2015.
    126) Product Information: glucagon injection powder for solution, glucagon injection powder for solution. Eli Lilly and Company, Indianapolis, IN, 2005.
    127) Product Information: glucagon injection, glucagon injection. Eli Lilly and Company, Indianapolis, IN, 2005.
    128) Product Information: glucagon rDNA origin intravenous injection, intramuscular injection, subcutaneous injection, glucagon rDNA origin intravenous injection, intramuscular injection, subcutaneous injection. Lilly USA, LLC (per DailyMed), Indianapolis, IN, 2012.
    129) Ranganath L, Schaper F, Gama R, et al: Mechanism of glucagon-induced nausea (letter). Clin Endocrinol 1999; 51:260-261.
    130) Rayburn W, Piehl E, & Sanfield J: Reversing severe hypoglycemia during pregnancy with glucagon therapy. Am J Peritinatol 1987; 4:259-261.
    131) Secco A, di Iorgi N, Napoli F, et al: The glucagon test in the diagnosis of growth hormone deficiency in children with short stature younger than 6 years. J Clin Endocrinol Metab 2009; 94(11):4251-4257.
    132) Seger DL: A critical reconsideration of the clinical effects and treatment recommendations for sodium channel blocking drug cardiotoxicity. Toxicol Rev 2006; 25(4):283-296.
    133) Sensky PR & Olczak SA: High-dose intravenous glucagon in severe tricyclic poisoning. Postgrad Med J 1999; 75(888):611-612.
    134) Shepherd G: Treatment of poisoning caused by beta-adrenergic and calcium-channel blockers. Am J Health Syst Pharm 2006; 63(19):1828-1835.
    135) Strich D , Terespolsky N , & Gillis D : Glucagon stimulation test for childhood growth hormone deficiency: timing of the peak is important. J Pediatr 2009; 154(3):415-419.
    136) Thoma ME, Glauser J, & Genuth S: Persistent hypoglycemia and hyperinsulinemia: caution in using glucagon. Am J Emerg Med 1996; 14(1):99-101.
    137) 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.
    138) 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.
    139) 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-.
    140) 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.
    141) 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.
    142) 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.
    143) 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.
    144) 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-.
    145) U.S. Occupational Safety, and Health Administration (OSHA): Process safety management of highly hazardous chemicals. 29 CFR 2010 2010; 29(1910.119):348-.
    146) 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.
    147) White CM: A review of potential cardiovascular uses of intravenous glucagon administration. J Clin Pharmacol 1999; 39(5):442-447.
    148) di Iorgi N, Napoli F, Allegri A, et al: The accuracy of the glucagon test compared to the insulin tolerance test in the diagnosis of adrenal insufficiency in young children with growth hormone deficiency. J Clin Endocrinol Metab 2010; 95(5):2132-2139.