Contact Us    Contact Us     |     Feedback
MOBILE VIEW  | 

VACOR

Export To Excel

Classification   |    Detailed evidence-based information

Substances Included Synonyms

Therapeutic Toxic Class

    A) Vacor(R) (PNU 2%) is a rodenticide marketed between 1975 and 1979 (Kenney et al, 1981).

Specific Substances

    1) DLP-87
    2) DLP 787
    3) PNU
    4) PYRIMINIL
    5) PYRIMINYL
    6) PYRIMINIL/VACOR
    7) PYRINURON
    8) RH-787
    9) VACOR
    10) CAS 53558-25-1
    1.2.1) MOLECULAR FORMULA
    1) C13-H12-N4-O3

Available Forms Sources

    A) FORMS
    1) PNU or pyriminil, alloxin, streptozocin and dithizone are substituted ureas.
    2) Vacor has the smell of peanuts (Johnson et al, 1980). Vacor does not actually contain peanut flavoring, but contains peanut oil which does not have the distinctive odor of peanuts (Litovitz, 1983).
    3) Vacor Rat Killer (yellow, resembles corn meal)
    4) DLP-787 2% Bait (yellow, resembles corn meal)
    5) DLP-787 10% House Mouse Tracking Powder (pale yellow to yellow-green powder)
    B) SOURCES
    1) Both DLP-787 2% Bait and DLP-787 10% House Mouse Tracking Powder are available only to Pest Control Operators.
    2) Vacor, 39 g, containing 2% PNU, has been removed from sale as of June, 1979 on the open market, but still is available to professional exterminators.
    C) USES
    1) These products contain the active ingredient RH-787, a single-dose, quick-kill rodenticide. They are used for control of Norway and roof rats, and the house mouse.

Overview

Life Support

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

Clinical Effects

    0.2.1) SUMMARY OF EXPOSURE
    A) MOST COMMON SIGNS/SYMPTOMS - Vacor(R) (PNU 2%) is an extremely toxic rodenticide that destroys pancreatic beta cells. Acute intentional ingestion frequently results in rapid onset of ketoacidosis-prone-insulin-dependent diabetes mellitus, severe persistent orthostatic hypotension, autonomic dysfunction (atonic esophagus, colon, bladder, pupils, impotence, decreased sweating, dysphagia), and sensorimotor peripheral neuropathy.
    1) Common presenting symptoms include nausea, abdominal pain, vomiting, blurred vision, polyuria, thirst, generalized weakness, and chills.
    B) COMMON SIGNS/SYMPTOMS - CNS findings are present in about 50% of deliberate overdose, including mildly decreased alertness, impaired memory, slurred speech, ataxia, myoclonus, choreiform movements, tremor, motor hyperactivity, EEG changes, nystagmus, hallucinations, delirium, confusion; can be acute or develop insidiously over several days.
    C) LESS COMMON SIGNS/SYMPTOMS - Mild pancreatitis, SIADH, diarrhea, cardiac arrhythmias, chest pain with ischemic EKG changes, ptosis, anorexia, generalized seizures, pneumonitis, and hypothermia have been reported.
    D) ONSET - Autonomic, peripheral, and CNS impairment often occurs within hours, but is occasionally delayed for up to 10 days. Onset of diabetes has varied from 4 hours to 7 days. Orthostatic hypotension is an early finding in about 50%, and is delayed for several days in the remainder.
    E) FATALITIES - Ingestion of as little as one-half of a single 39-gram package has resulted in death. Causes of death include ketoacidosis; perforations of esophagus, small bowel or colon; cardiac arrhythmias; and pneumonitis.
    F) EXPOSURE ROUTES - Most severe poisonings resulted from suicidal ingestion; systemic poisoning has not been reported from exposure by routes other than ingestion. Serious toxicity has rarely occurred following accidental ingestion in children.
    G) DECOMPOSITION PRODUCTS - When heated to decomposition, pyriminyl emits toxic fumes of oxides of nitrogen.
    0.2.3) VITAL SIGNS
    A) Severe persistent orthostatic hypotension is commonly reported.
    0.2.4) HEENT
    A) Miosis, visual field reduction, retinopathy, nystagmus, and unreactive or sluggishly reactive pupils may occur.
    0.2.5) CARDIOVASCULAR
    A) Severe persistent orthostatic hypotension occurs frequently within hours after ingestion of Vacor. Chest pain and cardiovascular collapse may occur.
    0.2.6) RESPIRATORY
    A) Chest pain and respiratory failure may occur.
    0.2.7) NEUROLOGIC
    A) MOST COMMON SIGNS/SYMPTOMS - Acute intentional ingestion frequently results in autonomic nervous system dysfunction (atonic esophagus, colon, bladder, pupils, impotence, decreased sweating, dysphagia), and sensorimotor peripheral neuropathy. Common presenting symptoms include generalized weakness, paresthesias, and loss of sensation.
    B) COMMON SIGNS/SYMPTOMS - CNS findings of encephalopathy are present in about 50% of deliberate overdoses, including mildly decreased alertness, impaired memory, slurred speech, ataxia, myoclonus, chorieform movements, tremor, motor hyperactivity, EEG changes, nystagmus, hallucinations, delirium, confusion; can be acute or develop insidiously over several days.
    C) LESS COMMON SIGNS/SYMPTOMS - Generalized seizures and coma have occasionally been reported.
    D) ONSET - Autonomic, peripheral, and CNS impairment often occurs within hours, but is occasionally delayed for up to 12 days.
    0.2.8) GASTROINTESTINAL
    A) Nausea, vomiting, abdominal pain, thirst, diarrhea, anorexia, mild pancreatitis, and hypomotility of the GI tract have been reported.
    0.2.9) HEPATIC
    A) Indications of liver injury have been reported in horses.
    0.2.10) GENITOURINARY
    A) Polyuria, glycosuria, and urinary retention have been reported.
    0.2.11) ACID-BASE
    A) A diabetic ketoacidosis-like reaction has been reported in several cases.
    0.2.15) MUSCULOSKELETAL
    A) Muscular weakness of the extremities has been reported.
    0.2.16) ENDOCRINE
    A) Initial hypoglycemia followed by persistent hyperglycemia (diabetes mellitus) is frequently reported following Vacor ingestion. Sweating, tachycardia, anxiety, and tremulousness may be absent during the initial hypoglycemic episode. The metabolic sequela of Vacor toxicity is an insulin dependent diabetes mellitus. SIADH has also been reported.
    0.2.20) REPRODUCTIVE
    A) At the time of this review, no data were available to assess the teratogenic potential of this agent.
    B) At the time of this review, no data were available to assess the potential effects of exposure to this agent during pregnancy or lactation.
    C) No information about possible male reproductive effects was found in available references at the time of this review.
    0.2.21) CARCINOGENICITY
    A) At the time of this review, no data were available to assess the carcinogenic potential of this agent.

Laboratory Monitoring

    A) Plasma Vacor levels are not clinically useful.
    B) Monitor blood and urine glucose, electrolytes, urinalysis, amylase, acid-base balance, ketones, and EKG carefully in symptomatic patients or in asymptomatic patients with history of deliberate ingestion.

Treatment Overview

    0.4.2) ORAL/PARENTERAL EXPOSURE
    A) EMESIS: Ipecac-induced emesis is not recommended because of the potential for CNS depression and seizures.
    B) ACTIVATED CHARCOAL: Administer charcoal as a slurry (240 mL water/30 g charcoal). Usual dose: 25 to 100 g in adults/adolescents, 25 to 50 g in children (1 to 12 years), and 1 g/kg in infants less than 1 year old.
    C) GASTRIC LAVAGE: Consider after ingestion of a potentially life-threatening amount of poison if it can be performed soon after ingestion (generally within 1 hour). Protect airway by placement in the head down left lateral decubitus position or by endotracheal intubation. Control any seizures first.
    1) CONTRAINDICATIONS: Loss of airway protective reflexes or decreased level of consciousness in unintubated patients; following ingestion of corrosives; hydrocarbons (high aspiration potential); patients at risk of hemorrhage or gastrointestinal perforation; and trivial or non-toxic ingestion.
    D) SEIZURES: Administer a benzodiazepine; DIAZEPAM (ADULT: 5 to 10 mg IV initially; repeat every 5 to 20 minutes as needed. CHILD: 0.1 to 0.5 mg/kg IV over 2 to 5 minutes; up to a maximum of 10 mg/dose. May repeat dose every 5 to 10 minutes as needed) or LORAZEPAM (ADULT: 2 to 4 mg IV initially; repeat every 5 to 10 minutes as needed, if seizures persist. CHILD: 0.05 to 0.1 mg/kg IV over 2 to 5 minutes, up to a maximum of 4 mg/dose; may repeat in 5 to 15 minutes as needed, if seizures continue).
    1) Consider phenobarbital or propofol if seizures recur after diazepam 30 mg (adults) or 10 mg (children greater than 5 years).
    2) Monitor for hypotension, dysrhythmias, respiratory depression, and need for endotracheal intubation. Evaluate for hypoglycemia, electrolyte disturbances, and hypoxia.
    E) NIACINAMIDE THERAPY - Niacinamide has been demonstrated to be an effective antidote to Vacor in the rat. Little experience is available of its antidotal efficacy following human exposure. Administration of niacinamide shortly after ingesting Vacor theoretically should offer protection.
    1) Dose of niacinamide: 500 mg IV or IM followed by 100 to 200 mg IV or IM every 4 hours to a total daily dose of 3 grams.
    2) Pediatric dose is one half of the suggested adult dose.
    3) Oral niacinamide (100 mg 3 to 5 times daily for 2 weeks) should be administered. There are no good data demonstrating the most effective therapy duration.
    F) INSULIN therapy should be instituted for probable onset of diabetes mellitus.
    G) MINERALOCORTICOID or other therapy may be necessary for severe orthostatic hypotension.
    0.4.3) INHALATION EXPOSURE
    A) Systemic poisoning has NOT been reported from routes of exposure other than ingestion. Carefully evaluate patients with inhalation exposure for the presence of toxicity BEFORE undertaking any of the following treatments.
    B) INHALATION: Move patient to fresh air. Monitor for respiratory distress. If cough or difficulty breathing develops, evaluate for respiratory tract irritation, bronchitis, or pneumonitis. Administer oxygen and assist ventilation as required. Treat bronchospasm with an inhaled beta2-adrenergic agonist. Consider systemic corticosteroids in patients with significant bronchospasm.
    C) SEIZURES: Administer a benzodiazepine; DIAZEPAM (ADULT: 5 to 10 mg IV initially; repeat every 5 to 20 minutes as needed. CHILD: 0.1 to 0.5 mg/kg IV over 2 to 5 minutes; up to a maximum of 10 mg/dose. May repeat dose every 5 to 10 minutes as needed) or LORAZEPAM (ADULT: 2 to 4 mg IV initially; repeat every 5 to 10 minutes as needed, if seizures persist. CHILD: 0.05 to 0.1 mg/kg IV over 2 to 5 minutes, up to a maximum of 4 mg/dose; may repeat in 5 to 15 minutes as needed, if seizures continue).
    1) Consider phenobarbital or propofol if seizures recur after diazepam 30 mg (adults) or 10 mg (children greater than 5 years).
    2) Monitor for hypotension, dysrhythmias, respiratory depression, and need for endotracheal intubation. Evaluate for hypoglycemia, electrolyte disturbances, and hypoxia.
    0.4.4) EYE EXPOSURE
    A) DECONTAMINATION: Remove contact lenses and irrigate exposed eyes with copious amounts of room temperature 0.9% saline or water for at least 15 minutes. If irritation, pain, swelling, lacrimation, or photophobia persist after 15 minutes of irrigation, the patient should be seen in a healthcare facility.
    0.4.5) DERMAL EXPOSURE
    A) OVERVIEW
    1) Systemic poisoning has NOT been reported from routes of exposure other than ingestion. Carefully evaluate patients with dermal exposure for the presence of toxicity BEFORE undertaking any of the following treatments.
    2) DECONTAMINATION: Remove contaminated clothing and jewelry and place them in plastic bags. Wash exposed areas with soap and water for 10 to 15 minutes with gentle sponging to avoid skin breakdown. A physician may need to examine the area if irritation or pain persists (Burgess et al, 1999).
    3) SEIZURES: Administer a benzodiazepine; DIAZEPAM (ADULT: 5 to 10 mg IV initially; repeat every 5 to 20 minutes as needed. CHILD: 0.1 to 0.5 mg/kg IV over 2 to 5 minutes; up to a maximum of 10 mg/dose. May repeat dose every 5 to 10 minutes as needed) or LORAZEPAM (ADULT: 2 to 4 mg IV initially; repeat every 5 to 10 minutes as needed, if seizures persist. CHILD: 0.05 to 0.1 mg/kg IV over 2 to 5 minutes, up to a maximum of 4 mg/dose; may repeat in 5 to 15 minutes as needed, if seizures continue).
    a) Consider phenobarbital or propofol if seizures recur after diazepam 30 mg (adults) or 10 mg (children greater than 5 years).
    b) Monitor for hypotension, dysrhythmias, respiratory depression, and need for endotracheal intubation. Evaluate for hypoglycemia, electrolyte disturbances, and hypoxia.

Range Of Toxicity

    A) Minimal lethal or toxic dose is not well established in the literature. Death has been reported following ingestion of one-half of a single 39 gram package.
    B) The estimated acute toxic dose of Vacor is 5 mg/kg. However, severity of intoxication must be based on clinical and laboratory findings.

Clinical Effects

Summary Of Exposure

    A) MOST COMMON SIGNS/SYMPTOMS - Vacor(R) (PNU 2%) is an extremely toxic rodenticide that destroys pancreatic beta cells. Acute intentional ingestion frequently results in rapid onset of ketoacidosis-prone-insulin-dependent diabetes mellitus, severe persistent orthostatic hypotension, autonomic dysfunction (atonic esophagus, colon, bladder, pupils, impotence, decreased sweating, dysphagia), and sensorimotor peripheral neuropathy.
    1) Common presenting symptoms include nausea, abdominal pain, vomiting, blurred vision, polyuria, thirst, generalized weakness, and chills.
    B) COMMON SIGNS/SYMPTOMS - CNS findings are present in about 50% of deliberate overdose, including mildly decreased alertness, impaired memory, slurred speech, ataxia, myoclonus, choreiform movements, tremor, motor hyperactivity, EEG changes, nystagmus, hallucinations, delirium, confusion; can be acute or develop insidiously over several days.
    C) LESS COMMON SIGNS/SYMPTOMS - Mild pancreatitis, SIADH, diarrhea, cardiac arrhythmias, chest pain with ischemic EKG changes, ptosis, anorexia, generalized seizures, pneumonitis, and hypothermia have been reported.
    D) ONSET - Autonomic, peripheral, and CNS impairment often occurs within hours, but is occasionally delayed for up to 10 days. Onset of diabetes has varied from 4 hours to 7 days. Orthostatic hypotension is an early finding in about 50%, and is delayed for several days in the remainder.
    E) FATALITIES - Ingestion of as little as one-half of a single 39-gram package has resulted in death. Causes of death include ketoacidosis; perforations of esophagus, small bowel or colon; cardiac arrhythmias; and pneumonitis.
    F) EXPOSURE ROUTES - Most severe poisonings resulted from suicidal ingestion; systemic poisoning has not been reported from exposure by routes other than ingestion. Serious toxicity has rarely occurred following accidental ingestion in children.
    G) DECOMPOSITION PRODUCTS - When heated to decomposition, pyriminyl emits toxic fumes of oxides of nitrogen.

Vital Signs

    3.3.1) SUMMARY
    A) Severe persistent orthostatic hypotension is commonly reported.
    3.3.4) BLOOD PRESSURE
    A) HYPOTENSION - Severe persistent orthostatic hypotension is commonly reported following Vacor intoxication. Onset may be delayed for a week after ingestion (Peoples & Maddy, 1979; LeWitt, 1980; Osterman et al, 1981; Kenney et al, 1981).

Heent

    3.4.1) SUMMARY
    A) Miosis, visual field reduction, retinopathy, nystagmus, and unreactive or sluggishly reactive pupils may occur.
    3.4.3) EYES
    A) MIOSIS - Eye involvement is usually limited to miosis with asymmetrical and sluggishly reactive pupils (Grant & Schuman, 1993).
    B) NYSTAGMUS is a manifestation of CNS involvement and is reported occasionally (Papasozomenos, 1980).
    C) PTOSIS of the eyelids has been reported (Grant & Schuman, 1993).
    D) PIGMENT RETINOPATHY was reported in two cases, occurring more than 4 years after ingestion. Concurrent ergotamine therapy may have contributed in one case. Pigmentation without visual impairment was produced with oral administration in the rabbit model; parenteral administration was not associated with ocular toxicity (Mindel et al, 1981; Mindel et al, 1988).
    E) VISUAL FIELD CONSTRICTION has been reported following Vacor(R) exposures.
    1) CASE REPORT - Severe visual field constriction, tunnel vision, and retinal edema were reported in one case of massive ingestion (Osterman et al, 1981).

Cardiovascular

    3.5.1) SUMMARY
    A) Severe persistent orthostatic hypotension occurs frequently within hours after ingestion of Vacor. Chest pain and cardiovascular collapse may occur.
    3.5.2) CLINICAL EFFECTS
    A) HYPOTENSIVE EPISODE
    1) Intermediate manifestations may include cardiovascular involvement such as atrial bigeminy (LeWitt, 1980). Late signs and symptoms may be indicative of cardiovascular collapse (Miller et al, 1978).
    B) ORTHOSTATIC HYPOTENSION
    1) Severe persistent orthostatic hypotension is commonly reported following Vacor intoxication which improves only minimally (LeWitt, 1980; Kenney et al, 1981) but may completely resolve within 11 months (Osterman et al, 1981). Onset may be delayed for a week after ingestion (Peoples & Maddy, 1979).
    C) CHEST PAIN
    1) Chest pain has been reported in suicide attempts (Pont et al, 1979).

Respiratory

    3.6.1) SUMMARY
    A) Chest pain and respiratory failure may occur.
    3.6.2) CLINICAL EFFECTS
    A) APNEA
    1) Intermediate symptoms may include chest pain followed by respiratory complications, such as bilateral bronchopneumonia. Respiratory failure may occur (EPA, 1977; Papasozomenos, 1980; Gallanosa et al, 1981).

Neurologic

    3.7.1) SUMMARY
    A) MOST COMMON SIGNS/SYMPTOMS - Acute intentional ingestion frequently results in autonomic nervous system dysfunction (atonic esophagus, colon, bladder, pupils, impotence, decreased sweating, dysphagia), and sensorimotor peripheral neuropathy. Common presenting symptoms include generalized weakness, paresthesias, and loss of sensation.
    B) COMMON SIGNS/SYMPTOMS - CNS findings of encephalopathy are present in about 50% of deliberate overdoses, including mildly decreased alertness, impaired memory, slurred speech, ataxia, myoclonus, chorieform movements, tremor, motor hyperactivity, EEG changes, nystagmus, hallucinations, delirium, confusion; can be acute or develop insidiously over several days.
    C) LESS COMMON SIGNS/SYMPTOMS - Generalized seizures and coma have occasionally been reported.
    D) ONSET - Autonomic, peripheral, and CNS impairment often occurs within hours, but is occasionally delayed for up to 12 days.
    3.7.2) CLINICAL EFFECTS
    A) DISORDER OF AUTONOMIC NERVOUS SYSTEM
    1) Severe and disabling autonomic impairment occurred in most cases of deliberate ingestion. The most predominant finding was postural hypotension, which could persist for years after exposure. Other autonomic findings were less persistent and included atonic esophagus, colon, bladder, and pupils. Symptoms included impotence, decreased sweating, urinary retention, and dysphagia (LeWitt, 1980; Rubenstein et al, 1980).
    B) SECONDARY PERIPHERAL NEUROPATHY
    1) Sensorimotor peripheral neuropathy developed in most patients after deliberate ingestion, often within the first 24 hours. Findings included loss of reflexes, impaired distal pinprick and vibratory sensation, paresthesias, and fine tremor of the extremities (LeWitt, 1980).
    2) Symptoms often progressed over several days; severe generalized weakness often lasted for weeks. Recovery was within one month in one-half of the patients (LeWitt, 1980; Pont et al, 1979; Gallanosa et al, 1981; Peoples & Maddy, 1979; Prosser & Karam, 1978).
    3) BURNING FEET - Severe burning feet have been reported following ingestion of Vacor-B. Vitamin B deficiency was suggested as a possible cause of this reaction (Lee & Kime, 1982).
    C) TOXIC ENCEPHALOPATHY
    1) CNS findings of encephalopathy are present in about 50% of deliberate overdoses including mildly decreased alertness, lethargy, stupor, impaired memory, slurred speech, ataxia, myoclonus, choreiform movements, tremor, motor hyperactivity, EEG changes, nystagmus, hallucinations, delirium, confusion; can be acute or develop insidiously over several days. Seizures, coma, and delayed encephalopathy are rarely reported (Gallanosa et al, 1981; LeWitt, 1980) Mindel, 1988; (Johnson et al, 1980).
    2) CASE REPORT - A 25-month-old child who ingested Vacor(R) had a major motor seizure before developing hyperglycemia (Johnson et al, 1980).
    3) CASE REPORT - A 48-year-old man developed delayed encephalopathy 12 days after ingestion, consisting of delirium and motor hyperactivity, with residual globally impaired intellectual function (LeWitt, 1980).
    4) CASE REPORT - Irreversible coma secondary to hypoglycemia has been reported following insulin treatment of Vacor-induced diabetes (Fears, 1980).

Gastrointestinal

    3.8.1) SUMMARY
    A) Nausea, vomiting, abdominal pain, thirst, diarrhea, anorexia, mild pancreatitis, and hypomotility of the GI tract have been reported.
    3.8.2) CLINICAL EFFECTS
    A) VOMITING
    1) Initial symptoms include nausea, abdominal pain, and emesis (Johnson et al, 1980; Pont et al, 1979).
    B) LOSS OF APPETITE
    1) Anorexia may be an intermediate symptom of intoxication (Gallanosa et al, 1981; Johnson et al, 1980).
    C) DRUG-INDUCED ILEUS
    1) Ileus may occur and intestinal perforations have been reported (Kenney et al, 1981; Miller et al, 1978).
    D) THIRST FINDING
    1) Thirst has been reported in several ingestions (Osterman et al, 1981; Kenney et al, 1981).
    E) DIARRHEA
    1) Severe diarrhea may occur (Miller et al, 1978).
    F) PANCREATITIS
    1) Mild pancreatitis has been reported (Pont et al, 1979).

Hepatic

    3.9.1) SUMMARY
    A) Indications of liver injury have been reported in horses.
    3.9.3) ANIMAL EFFECTS
    A) ANIMAL STUDIES
    1) HEPATOCELLULAR DAMAGE
    a) HORSES - Acute exposure in horses has resulted in indications of liver injury (HSDB , 2000).

Genitourinary

    3.10.1) SUMMARY
    A) Polyuria, glycosuria, and urinary retention have been reported.
    3.10.2) CLINICAL EFFECTS
    A) RETENTION OF URINE
    1) Urinary retention and bladder atony may occur. Reversible loss of bladder control has been reported frequently (Kenney et al, 1981; Osterman et al, 1981; Gallanosa et al, 1981).
    B) GLYCOSURIA
    1) Glycosuria and polyuria have been reported to occur approximately a week after ingestion (Peoples & Maddy, 1979; HSDB , 2000).

Acid-Base

    3.11.1) SUMMARY
    A) A diabetic ketoacidosis-like reaction has been reported in several cases.
    3.11.2) CLINICAL EFFECTS
    A) KETOSIS
    1) A diabetic ketoacidosis-like reaction has been reported in several cases (Gallanosa et al, 1981; Kenney et al, 1981; Peoples & Maddy, 1979).

Musculoskeletal

    3.15.1) SUMMARY
    A) Muscular weakness of the extremities has been reported.
    3.15.2) CLINICAL EFFECTS
    A) MUSCLE WEAKNESS
    1) Muscular weakness of the extremities has been reported after ingestion (Gallanosa et al, 1981).

Endocrine

    3.16.1) SUMMARY
    A) Initial hypoglycemia followed by persistent hyperglycemia (diabetes mellitus) is frequently reported following Vacor ingestion. Sweating, tachycardia, anxiety, and tremulousness may be absent during the initial hypoglycemic episode. The metabolic sequela of Vacor toxicity is an insulin dependent diabetes mellitus. SIADH has also been reported.
    3.16.2) CLINICAL EFFECTS
    A) HYPERGLYCEMIA
    1) Onset of hyperglycemia may occur in a few hours or be delayed up to 2 weeks. Diabetes mellitus associated with autonomic and peripheral neuropathy has been reported. Diabetes is a late and persistent result of Vacor intoxication (Peoples & Maddy, 1979; Gallanosa et al, 1981).
    3.16.3) ANIMAL EFFECTS
    A) ANIMAL STUDIES
    1) HYPERGLYCEMIA
    a) In vitro, Vacor suppressed glucose-stimulated release of insulin (Taniguchi et al, 1989).

Reproductive

    3.20.1) SUMMARY
    A) At the time of this review, no data were available to assess the teratogenic potential of this agent.
    B) At the time of this review, no data were available to assess the potential effects of exposure to this agent during pregnancy or lactation.
    C) No information about possible male reproductive effects was found in available references at the time of this review.
    3.20.4) EFFECTS DURING BREAST-FEEDING
    A) LACK OF INFORMATION
    1) At the time of this review, no data were available to assess the potential effects of exposure to this agent during lactation.

Carcinogenicity

    3.21.1) IARC CATEGORY
    A) IARC Carcinogenicity Ratings for CAS53558-25-1 (International Agency for Research on Cancer (IARC), 2016; International Agency for Research on Cancer, 2015; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2010; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2010a; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2008; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2007; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2006; IARC, 2004):
    1) Not Listed
    3.21.2) SUMMARY/HUMAN
    A) At the time of this review, no data were available to assess the carcinogenic potential of this agent.
    3.21.3) HUMAN STUDIES
    A) LACK OF INFORMATION
    1) At the time of this review, no data were available to assess the carcinogenic potential of this agent.

Genotoxicity

    A) At the time of this review, no data were available to assess the mutagenic or genotoxic potential of this agent.

Laboratory Monitoring

Monitoring Parameters Levels

    4.1.1) SUMMARY
    A) Plasma Vacor levels are not clinically useful.
    B) Monitor blood and urine glucose, electrolytes, urinalysis, amylase, acid-base balance, ketones, and EKG carefully in symptomatic patients or in asymptomatic patients with history of deliberate ingestion.
    4.1.2) SERUM/BLOOD
    A) BLOOD/SERUM CHEMISTRY
    1) Monitor serum glucose levels and amylase (Gallanosa et al, 1981).
    B) ACID/BASE
    1) Monitor acid-base balance.
    4.1.3) URINE
    A) URINALYSIS
    1) Monitor urine glucose and ketone concentrations (Morgan, 1989).
    4.1.4) OTHER
    A) OTHER
    1) ECG
    a) Monitor electrocardiogram for arrhythmias (Morgan, 1989).

Methods

    A) OTHER
    1) POLAROGRAPHY - Pulse polarography has been used to recover RH787 spikes in human liver samples (Whittaker & Osteryoung, 1976).

Treatment

Life Support

    A) Support respiratory and cardiovascular function.

Monitoring

    A) Plasma Vacor levels are not clinically useful.
    B) Monitor blood and urine glucose, electrolytes, urinalysis, amylase, acid-base balance, ketones, and EKG carefully in symptomatic patients or in asymptomatic patients with history of deliberate ingestion.

Oral Exposure

    6.5.1) PREVENTION OF ABSORPTION/PREHOSPITAL
    A) EMESIS/NOT RECOMMENDED
    1) EMESIS: Ipecac-induced emesis is not recommended because of the potential for CNS depression and seizures.
    B) ACTIVATED CHARCOAL
    1) PREHOSPITAL ACTIVATED CHARCOAL ADMINISTRATION
    a) Consider prehospital administration of activated charcoal as an aqueous slurry in patients with a potentially toxic ingestion who are awake and able to protect their airway. Activated charcoal is most effective when administered within one hour of ingestion. Administration in the prehospital setting has the potential to significantly decrease the time from toxin ingestion to activated charcoal administration, although it has not been shown to affect outcome (Alaspaa et al, 2005; Thakore & Murphy, 2002; Spiller & Rogers, 2002).
    1) In patients who are at risk for the abrupt onset of seizures or mental status depression, activated charcoal should not be administered in the prehospital setting, due to the risk of aspiration in the event of spontaneous emesis.
    2) The addition of flavoring agents (cola drinks, chocolate milk, cherry syrup) to activated charcoal improves the palatability for children and may facilitate successful administration (Guenther Skokan et al, 2001; Dagnone et al, 2002).
    2) CHARCOAL DOSE
    a) Use a minimum of 240 milliliters of water per 30 grams charcoal (FDA, 1985). Optimum dose not established; usual dose is 25 to 100 grams in adults and adolescents; 25 to 50 grams in children aged 1 to 12 years (or 0.5 to 1 gram/kilogram body weight) ; and 0.5 to 1 gram/kilogram in infants up to 1 year old (Chyka et al, 2005).
    1) Routine use of a cathartic with activated charcoal is NOT recommended as there is no evidence that cathartics reduce drug absorption and cathartics are known to cause adverse effects such as nausea, vomiting, abdominal cramps, electrolyte imbalances and occasionally hypotension (None Listed, 2004).
    b) ADVERSE EFFECTS/CONTRAINDICATIONS
    1) Complications: emesis, aspiration (Chyka et al, 2005). Aspiration may be complicated by acute respiratory failure, ARDS, bronchiolitis obliterans or chronic lung disease (Golej et al, 2001; Graff et al, 2002; Pollack et al, 1981; Harris & Filandrinos, 1993; Elliot et al, 1989; Rau et al, 1988; Golej et al, 2001; Graff et al, 2002). Refer to the ACTIVATED CHARCOAL/TREATMENT management for further information.
    2) Contraindications: unprotected airway (increases risk/severity of aspiration) , nonfunctioning gastrointestinal tract, uncontrolled vomiting, and ingestion of most hydrocarbons (Chyka et al, 2005).
    6.5.2) PREVENTION OF ABSORPTION
    A) EMESIS/NOT RECOMMENDED
    1) EMESIS: Ipecac-induced emesis is not recommended because of the potential for CNS depression and seizures.
    B) ACTIVATED CHARCOAL
    1) CHARCOAL ADMINISTRATION
    a) Consider administration of activated charcoal after a potentially toxic ingestion (Chyka et al, 2005). Administer charcoal as an aqueous slurry; most effective when administered within one hour of ingestion.
    2) CHARCOAL DOSE
    a) Use a minimum of 240 milliliters of water per 30 grams charcoal (FDA, 1985). Optimum dose not established; usual dose is 25 to 100 grams in adults and adolescents; 25 to 50 grams in children aged 1 to 12 years (or 0.5 to 1 gram/kilogram body weight) ; and 0.5 to 1 gram/kilogram in infants up to 1 year old (Chyka et al, 2005).
    1) Routine use of a cathartic with activated charcoal is NOT recommended as there is no evidence that cathartics reduce drug absorption and cathartics are known to cause adverse effects such as nausea, vomiting, abdominal cramps, electrolyte imbalances and occasionally hypotension (None Listed, 2004).
    b) ADVERSE EFFECTS/CONTRAINDICATIONS
    1) Complications: emesis, aspiration (Chyka et al, 2005). Aspiration may be complicated by acute respiratory failure, ARDS, bronchiolitis obliterans or chronic lung disease (Golej et al, 2001; Graff et al, 2002; Pollack et al, 1981; Harris & Filandrinos, 1993; Elliot et al, 1989; Rau et al, 1988; Golej et al, 2001; Graff et al, 2002). Refer to the ACTIVATED CHARCOAL/TREATMENT management for further information.
    2) Contraindications: unprotected airway (increases risk/severity of aspiration) , nonfunctioning gastrointestinal tract, uncontrolled vomiting, and ingestion of most hydrocarbons (Chyka et al, 2005).
    C) GASTRIC LAVAGE
    1) INDICATIONS: Consider gastric lavage with a large-bore orogastric tube (ADULT: 36 to 40 French or 30 English gauge tube {external diameter 12 to 13.3 mm}; CHILD: 24 to 28 French {diameter 7.8 to 9.3 mm}) after a potentially life threatening ingestion if it can be performed soon after ingestion (generally within 60 minutes).
    a) Consider lavage more than 60 minutes after ingestion of sustained-release formulations and substances known to form bezoars or concretions.
    2) PRECAUTIONS:
    a) SEIZURE CONTROL: Is mandatory prior to gastric lavage.
    b) AIRWAY PROTECTION: Place patients in the head down left lateral decubitus position, with suction available. Patients with depressed mental status should be intubated with a cuffed endotracheal tube prior to lavage.
    3) LAVAGE FLUID:
    a) Use small aliquots of liquid. Lavage with 200 to 300 milliliters warm tap water (preferably 38 degrees Celsius) or saline per wash (in older children or adults) and 10 milliliters/kilogram body weight of normal saline in young children(Vale et al, 2004) and repeat until lavage return is clear.
    b) The volume of lavage return should approximate amount of fluid given to avoid fluid-electrolyte imbalance.
    c) CAUTION: Water should be avoided in young children because of the risk of electrolyte imbalance and water intoxication. Warm fluids avoid the risk of hypothermia in very young children and the elderly.
    4) COMPLICATIONS:
    a) Complications of gastric lavage have included: aspiration pneumonia, hypoxia, hypercapnia, mechanical injury to the throat, esophagus, or stomach, fluid and electrolyte imbalance (Vale, 1997). Combative patients may be at greater risk for complications (Caravati et al, 2001).
    b) Gastric lavage can cause significant morbidity; it should NOT be performed routinely in all poisoned patients (Vale, 1997).
    5) CONTRAINDICATIONS:
    a) Loss of airway protective reflexes or decreased level of consciousness if patient is not intubated, following ingestion of corrosive substances, hydrocarbons (high aspiration potential), patients at risk of hemorrhage or gastrointestinal perforation, or trivial or non-toxic ingestion.
    6.5.3) TREATMENT
    A) SEIZURE
    1) SUMMARY
    a) Attempt initial control with a benzodiazepine (eg, diazepam, lorazepam). If seizures persist or recur, administer phenobarbital or propofol.
    b) Monitor for respiratory depression, hypotension, and dysrhythmias. Endotracheal intubation should be performed in patients with persistent seizures.
    c) Evaluate for hypoxia, electrolyte disturbances, and hypoglycemia (or, if immediate bedside glucose testing is not available, treat with intravenous dextrose).
    2) DIAZEPAM
    a) ADULT DOSE: Initially 5 to 10 mg IV, OR 0.15 mg/kg IV up to 10 mg per dose up to a rate of 5 mg/minute; may be repeated every 5 to 20 minutes as needed (Brophy et al, 2012; Prod Info diazepam IM, IV injection, 2008; Manno, 2003).
    b) PEDIATRIC DOSE: 0.1 to 0.5 mg/kg IV over 2 to 5 minutes; up to a maximum of 10 mg/dose. May repeat dose every 5 to 10 minutes as needed (Loddenkemper & Goodkin, 2011; Hegenbarth & American Academy of Pediatrics Committee on Drugs, 2008).
    c) Monitor for hypotension, respiratory depression, and the need for endotracheal intubation. Consider a second agent if seizures persist or recur after repeated doses of diazepam .
    3) NO INTRAVENOUS ACCESS
    a) DIAZEPAM may be given rectally or intramuscularly (Manno, 2003). RECTAL DOSE: CHILD: Greater than 12 years: 0.2 mg/kg; 6 to 11 years: 0.3 mg/kg; 2 to 5 years: 0.5 mg/kg (Brophy et al, 2012).
    b) MIDAZOLAM has been used intramuscularly and intranasally, particularly in children when intravenous access has not been established. ADULT DOSE: 0.2 mg/kg IM, up to a maximum dose of 10 mg (Brophy et al, 2012). PEDIATRIC DOSE: INTRAMUSCULAR: 0.2 mg/kg IM, up to a maximum dose of 7 mg (Chamberlain et al, 1997) OR 10 mg IM (weight greater than 40 kg); 5 mg IM (weight 13 to 40 kg); INTRANASAL: 0.2 to 0.5 mg/kg up to a maximum of 10 mg/dose (Loddenkemper & Goodkin, 2011; Brophy et al, 2012). BUCCAL midazolam, 10 mg, has been used in adolescents and older children (5-years-old or more) to control seizures when intravenous access was not established (Scott et al, 1999).
    4) LORAZEPAM
    a) MAXIMUM RATE: The rate of intravenous administration of lorazepam should not exceed 2 mg/min (Brophy et al, 2012; Prod Info lorazepam IM, IV injection, 2008).
    b) ADULT DOSE: 2 to 4 mg IV initially; repeat every 5 to 10 minutes as needed, if seizures persist (Manno, 2003; Brophy et al, 2012).
    c) PEDIATRIC DOSE: 0.05 to 0.1 mg/kg IV over 2 to 5 minutes, up to a maximum of 4 mg/dose; may repeat in 5 to 15 minutes as needed, if seizures continue (Brophy et al, 2012; Loddenkemper & Goodkin, 2011; Hegenbarth & American Academy of Pediatrics Committee on Drugs, 2008; Sreenath et al, 2009; Chin et al, 2008).
    5) PHENOBARBITAL
    a) ADULT LOADING DOSE: 20 mg/kg IV at an infusion rate of 50 to 100 mg/minute IV. An additional 5 to 10 mg/kg dose may be given 10 minutes after loading infusion if seizures persist or recur (Brophy et al, 2012).
    b) Patients receiving high doses will require endotracheal intubation and may require vasopressor support (Brophy et al, 2012).
    c) PEDIATRIC LOADING DOSE: 20 mg/kg may be given as single or divided application (2 mg/kg/minute in children weighing less than 40 kg up to 100 mg/min in children weighing greater than 40 kg). A plasma concentration of about 20 mg/L will be achieved by this dose (Loddenkemper & Goodkin, 2011).
    d) REPEAT PEDIATRIC DOSE: Repeat doses of 5 to 20 mg/kg may be given every 15 to 20 minutes if seizures persist, with cardiorespiratory monitoring (Loddenkemper & Goodkin, 2011).
    e) MONITOR: For hypotension, respiratory depression, and the need for endotracheal intubation (Loddenkemper & Goodkin, 2011; Manno, 2003).
    f) SERUM CONCENTRATION MONITORING: Monitor serum concentrations over the next 12 to 24 hours. Therapeutic serum concentrations of phenobarbital range from 10 to 40 mcg/mL, although the optimal plasma concentration for some individuals may vary outside this range (Hvidberg & Dam, 1976; Choonara & Rane, 1990; AMA Department of Drugs, 1992).
    6) OTHER AGENTS
    a) If seizures persist after phenobarbital, propofol or pentobarbital infusion, or neuromuscular paralysis with general anesthesia (isoflurane) and continuous EEG monitoring should be considered (Manno, 2003). Other anticonvulsants can be considered (eg, valproate sodium, levetiracetam, lacosamide, topiramate) if seizures persist or recur; however, there is very little data regarding their use in toxin induced seizures, controlled trials are not available to define the optimal dosage ranges for these agents in status epilepticus (Brophy et al, 2012):
    1) VALPROATE SODIUM: ADULT DOSE: An initial dose of 20 to 40 mg/kg IV, at a rate of 3 to 6 mg/kg/minute; may give an additional dose of 20 mg/kg 10 minutes after loading infusion. PEDIATRIC DOSE: 1.5 to 3 mg/kg/minute (Brophy et al, 2012).
    2) LEVETIRACETAM: ADULT DOSE: 1000 to 3000 mg IV, at a rate of 2 to 5 mg/kg/min IV. PEDIATRIC DOSE: 20 to 60 mg/kg IV (Brophy et al, 2012; Loddenkemper & Goodkin, 2011).
    3) LACOSAMIDE: ADULT DOSE: 200 to 400 mg IV; 200 mg IV over 15 minutes (Brophy et al, 2012). PEDIATRIC DOSE: In one study, median starting doses of 1.3 mg/kg/day and maintenance doses of 4.7 mg/kg/day were used in children 8 years and older (Loddenkemper & Goodkin, 2011).
    4) TOPIRAMATE: ADULT DOSE: 200 to 400 mg nasogastric/orally OR 300 to 1600 mg/day orally divided in 2 to 4 times daily (Brophy et al, 2012).
    B) NIACINAMIDE
    1) NOTE - NIACINAMIDE INJECTION IS NO LONGER COMMERCIALLY AVAILABLE
    a) IN THE UNITED STATES.
    2) NIACINAMIDE (not niacin or nicotinic acid): Has been demonstrated to be an effective antidote for streptozocin, alloxan, and pyriminil in the rat (Ganda et al, 1976; Rossini et al, 1975).
    a) In humans, little experience has been obtained using nicotinamide as an antidote. It appears to be most effective when given early after an ingestion, with less or no effect when given later. In one case where it was given 9 hours postingestion and another 14 hours postingestion, there was no appreciable effect (Pont et al, 1979).
    b) Nevertheless, the administration of large parenteral doses of niacinamide should be considered by the attending physician in those cases where Vacor or DLP-787 has been ingested.
    3) INTRAVENOUS DOSE - Initial dose ADULT: 500 milligrams intramuscularly or intravenously (slowly), follow with 100 to 200 milligrams intramuscularly or intravenously every 4 hours for up to 48 hours (Prod Info, 1976; (Howland et al, 1986). Adult dosage is 2 to 3 grams per day. CHILDREN - half the suggested adult dosage.
    4) MAXIMUM DOSE
    a) If signs of Vacor toxicity appear, niacinamide can be given every 2 hours but not to exceed a total of 3 grams each day for adults (Prod Info, 1976; (Miller et al, 1978).
    5) ORAL DOSE - Niacinamide 100 milligrams three to five times daily for two weeks can be administered. Treatment should be started as soon as possible after acute ingestion (Prod Info, 1976).
    6) LATE TREATMENT
    a) The experience with the initial use of niacinamide 3 to 4 days after the acute ingestion had taken place has not convincingly demonstrated improvement in the clinical course or outcome.
    7) Nicotinic acid has not been used in place of niacinamide. Animal studies have shown that nicotinic acid (niacin) has no effect on preventing diabetes, presumably due to inability to be taken up by pancreatic islet cells (Johnson et al, 1980).
    C) INSULIN (CLASS)
    1) Therapy for insulin dependent diabetes may be necessary.
    D) HYPOTENSIVE EPISODE
    1) Mineralocorticoids such as fludrocortisone (0.3 to 0.6 milligram/day) or deoxycorticosterone acetate (20 milligrams/day) have used with moderate success to treat the orthostatic hypotension.
    2) Dihydroergotamine was successfully used to treat hypotension refractory to steroids in one case (Benowitz et al, 1980), but was unsuccessful in another (Osterman et al, 1981).
    3) Oral ergotamine tartrate has been useful. However, the patient subsequently developed a bilateral toxic retinal vasculopathy, an extinguished electroretinogram, and a reduced dark-adaptation retinal sensitivity. These findings could have been attributed to Vacor toxicity, ergotamine toxicity, or a combination of the two (Mindel et al, 1981).
    4) Fluid loading, sodium loading, and elastic stockings are other measures that have been tried (Osterman et al, 1981; Benowitz et al, 1980).
    E) MONITORING OF PATIENT
    1) Monitor cardiac function and electrolyte balance closely.
    F) EXPERIMENTAL THERAPY
    1) OCULAR TOXICITY
    a) In rabbits, gentamicin 1 gram in 10 milliliters of water given orally 4 hours before, 1 hour before, and 4 hours after an oral dose of PNU 125 milligrams/kilogram was effective in preventing PNU-associated ocular toxicity (Mindel et al, 1988). Additional studies are needed to evaluate the efficacy of this treatment in humans.

Inhalation Exposure

    6.7.1) DECONTAMINATION
    A) Move patient from the toxic environment to fresh air. Monitor for respiratory distress. If cough or difficulty in breathing develops, evaluate for hypoxia, respiratory tract irritation, bronchitis, or pneumonitis.
    B) OBSERVATION: Carefully observe patients with inhalation exposure for the development of any systemic signs or symptoms and administer symptomatic treatment as necessary.
    C) INITIAL TREATMENT: Administer 100% humidified supplemental oxygen, perform endotracheal intubation and provide assisted ventilation as required. Administer inhaled beta-2 adrenergic agonists, if bronchospasm develops. Consider systemic corticosteroids in patients with significant bronchospasm (National Heart,Lung,and Blood Institute, 2007). Exposed skin and eyes should be flushed with copious amounts of water.
    6.7.2) TREATMENT
    A) PULMONARY ABSORPTION
    1) Systemic poisoning has NOT been reported from routes of exposure other than ingestion (EPA, 1985). Carefully evaluate patients with inhalation exposure for the presence of toxicity BEFORE undertaking any of the following treatments.
    B) SEIZURE
    1) SUMMARY
    a) Attempt initial control with a benzodiazepine (eg, diazepam, lorazepam). If seizures persist or recur, administer phenobarbital or propofol.
    b) Monitor for respiratory depression, hypotension, and dysrhythmias. Endotracheal intubation should be performed in patients with persistent seizures.
    c) Evaluate for hypoxia, electrolyte disturbances, and hypoglycemia (or, if immediate bedside glucose testing is not available, treat with intravenous dextrose).
    2) DIAZEPAM
    a) ADULT DOSE: Initially 5 to 10 mg IV, OR 0.15 mg/kg IV up to 10 mg per dose up to a rate of 5 mg/minute; may be repeated every 5 to 20 minutes as needed (Brophy et al, 2012; Prod Info diazepam IM, IV injection, 2008; Manno, 2003).
    b) PEDIATRIC DOSE: 0.1 to 0.5 mg/kg IV over 2 to 5 minutes; up to a maximum of 10 mg/dose. May repeat dose every 5 to 10 minutes as needed (Loddenkemper & Goodkin, 2011; Hegenbarth & American Academy of Pediatrics Committee on Drugs, 2008).
    c) Monitor for hypotension, respiratory depression, and the need for endotracheal intubation. Consider a second agent if seizures persist or recur after repeated doses of diazepam .
    3) NO INTRAVENOUS ACCESS
    a) DIAZEPAM may be given rectally or intramuscularly (Manno, 2003). RECTAL DOSE: CHILD: Greater than 12 years: 0.2 mg/kg; 6 to 11 years: 0.3 mg/kg; 2 to 5 years: 0.5 mg/kg (Brophy et al, 2012).
    b) MIDAZOLAM has been used intramuscularly and intranasally, particularly in children when intravenous access has not been established. ADULT DOSE: 0.2 mg/kg IM, up to a maximum dose of 10 mg (Brophy et al, 2012). PEDIATRIC DOSE: INTRAMUSCULAR: 0.2 mg/kg IM, up to a maximum dose of 7 mg (Chamberlain et al, 1997) OR 10 mg IM (weight greater than 40 kg); 5 mg IM (weight 13 to 40 kg); INTRANASAL: 0.2 to 0.5 mg/kg up to a maximum of 10 mg/dose (Loddenkemper & Goodkin, 2011; Brophy et al, 2012). BUCCAL midazolam, 10 mg, has been used in adolescents and older children (5-years-old or more) to control seizures when intravenous access was not established (Scott et al, 1999).
    4) LORAZEPAM
    a) MAXIMUM RATE: The rate of intravenous administration of lorazepam should not exceed 2 mg/min (Brophy et al, 2012; Prod Info lorazepam IM, IV injection, 2008).
    b) ADULT DOSE: 2 to 4 mg IV initially; repeat every 5 to 10 minutes as needed, if seizures persist (Manno, 2003; Brophy et al, 2012).
    c) PEDIATRIC DOSE: 0.05 to 0.1 mg/kg IV over 2 to 5 minutes, up to a maximum of 4 mg/dose; may repeat in 5 to 15 minutes as needed, if seizures continue (Brophy et al, 2012; Loddenkemper & Goodkin, 2011; Hegenbarth & American Academy of Pediatrics Committee on Drugs, 2008; Sreenath et al, 2009; Chin et al, 2008).
    5) PHENOBARBITAL
    a) ADULT LOADING DOSE: 20 mg/kg IV at an infusion rate of 50 to 100 mg/minute IV. An additional 5 to 10 mg/kg dose may be given 10 minutes after loading infusion if seizures persist or recur (Brophy et al, 2012).
    b) Patients receiving high doses will require endotracheal intubation and may require vasopressor support (Brophy et al, 2012).
    c) PEDIATRIC LOADING DOSE: 20 mg/kg may be given as single or divided application (2 mg/kg/minute in children weighing less than 40 kg up to 100 mg/min in children weighing greater than 40 kg). A plasma concentration of about 20 mg/L will be achieved by this dose (Loddenkemper & Goodkin, 2011).
    d) REPEAT PEDIATRIC DOSE: Repeat doses of 5 to 20 mg/kg may be given every 15 to 20 minutes if seizures persist, with cardiorespiratory monitoring (Loddenkemper & Goodkin, 2011).
    e) MONITOR: For hypotension, respiratory depression, and the need for endotracheal intubation (Loddenkemper & Goodkin, 2011; Manno, 2003).
    f) SERUM CONCENTRATION MONITORING: Monitor serum concentrations over the next 12 to 24 hours. Therapeutic serum concentrations of phenobarbital range from 10 to 40 mcg/mL, although the optimal plasma concentration for some individuals may vary outside this range (Hvidberg & Dam, 1976; Choonara & Rane, 1990; AMA Department of Drugs, 1992).
    6) OTHER AGENTS
    a) If seizures persist after phenobarbital, propofol or pentobarbital infusion, or neuromuscular paralysis with general anesthesia (isoflurane) and continuous EEG monitoring should be considered (Manno, 2003). Other anticonvulsants can be considered (eg, valproate sodium, levetiracetam, lacosamide, topiramate) if seizures persist or recur; however, there is very little data regarding their use in toxin induced seizures, controlled trials are not available to define the optimal dosage ranges for these agents in status epilepticus (Brophy et al, 2012):
    1) VALPROATE SODIUM: ADULT DOSE: An initial dose of 20 to 40 mg/kg IV, at a rate of 3 to 6 mg/kg/minute; may give an additional dose of 20 mg/kg 10 minutes after loading infusion. PEDIATRIC DOSE: 1.5 to 3 mg/kg/minute (Brophy et al, 2012).
    2) LEVETIRACETAM: ADULT DOSE: 1000 to 3000 mg IV, at a rate of 2 to 5 mg/kg/min IV. PEDIATRIC DOSE: 20 to 60 mg/kg IV (Brophy et al, 2012; Loddenkemper & Goodkin, 2011).
    3) LACOSAMIDE: ADULT DOSE: 200 to 400 mg IV; 200 mg IV over 15 minutes (Brophy et al, 2012). PEDIATRIC DOSE: In one study, median starting doses of 1.3 mg/kg/day and maintenance doses of 4.7 mg/kg/day were used in children 8 years and older (Loddenkemper & Goodkin, 2011).
    4) TOPIRAMATE: ADULT DOSE: 200 to 400 mg nasogastric/orally OR 300 to 1600 mg/day orally divided in 2 to 4 times daily (Brophy et al, 2012).
    C) NIACINAMIDE
    1) NOTE: NIACINAMIDE INJECTION IS NO LONGER COMMERCIALLY
    a) AVAILABLE IN THE UNITED STATES.
    2) NIACINAMIDE (not niacin or nicotinic acid): Has been demonstrated to be an effective antidote for streptozocin, alloxan, and pyriminil in the rat (Ganda et al, 1976; Rossini et al, 1975).
    a) In humans, little experience has been obtained using nicotinamide as an antidote. It appears to be most effective when given early after an ingestion, with less or no effect when given later. In one case where it was given 9 hours postingestion and another 14 hours postingestion, there was no appreciable effect (Pont et al, 1979).
    b) Nevertheless, the administration of large parenteral doses of niacinamide should be considered by the attending physician in those cases where Vacor or DLP-787 has been ingested.
    3) INTRAVENOUS DOSE - Initial dose Adult: 500 milligrams intramuscularly or intravenously (slowly), follow with 100 to 400 milligrams intramuscularly or intravenously every 4 hours for up to 48 hours (Prod Info, 1976; (Howland et al, 1986). Adult dosage is 2 to 3 grams per day. CHILDREN: half the suggested adult dosage.
    4) MAXIMUM DOSE - If signs of Vacor toxicity appear, niacinamide can be given every 2 hours but not to exceed a total of 3 grams each day for adults (Prod Info, 1976; (Miller et al, 1978).
    5) ORAL DOSE - Niacinamide 100 milligrams three to five times daily for two weeks can be administered. Treatment should be started as soon as possible after acute ingestion (Prod Info, 1976).
    6) LATE TREATMENT - The experience with the initial use of niacinamide 3 to 4 days after the acute ingestion had taken place has not convincingly demonstrated improvement in the clinical course or outcome.
    7) Nicotinic acid has not been used in place of niacinamide. Animal studies have shown that nicotinic acid (niacin) has no effect on preventing diabetes, presumably due to inability to be taken up by pancreatic islet cells (Johnson et al, 1980).
    D) INSULIN (CLASS)
    1) Therapy for insulin dependent diabetics may be necessary.
    E) HYPOTENSIVE EPISODE
    1) Mineralocorticoids such as fludrocortisone (0.3 to 0.6 milligrams/day) or deoxycorticosterone acetate (20 milligrams/day) have been used with moderate success to treat the orthostatic hypotension.
    2) Dihydroergotamine was successfully used to treat hypotension refractory to steroids in one case (Benowitz et al, 1980), but was unsuccessful in another (Osterman et al, 1981).
    3) Oral ergotamine tartrate has been useful. However, the patient subsequently developed a bilateral toxic retinal vasculopathy, an extinguished electroretinogram, and a reduced dark-adaptation retinal sensitivity. These findings could have been attributed to vacor toxicity, ergotamine toxicity, or a combination of the two (Mindel et al, 1981).
    4) Fluid loading, sodium loading, and elastic stockings are other measures that have been tried (Osterman et al, 1981; Benowitz et al, 1980).
    F) MONITORING OF PATIENT
    1) Monitor cardiac function and electrolyte balance closely.
    G) EXPERIMENTAL THERAPY
    1) OCULAR TOXICITY
    a) In rabbits, gentamicin 1 gram in 10 milliliters of water given orally 4 hours before, 1 hour before, and 4 hours after an oral dose of PNU 125 milligrams/kilogram was effective in preventing PNU-associated ocular toxicity (Mindel et al, 1988). Additional studies are needed to evaluate the efficacy of this treatment in humans.
    H) Treatment should include recommendations listed in the ORAL EXPOSURE section when appropriate.

Eye Exposure

    6.8.1) DECONTAMINATION
    A) EYE IRRIGATION, ROUTINE: Remove contact lenses and irrigate exposed eyes with copious amounts of room temperature 0.9% saline or water for at least 15 minutes. If irritation, pain, swelling, lacrimation, or photophobia persist after 15 minutes of irrigation, an ophthalmologic examination should be performed (Peate, 2007; Naradzay & Barish, 2006).

Dermal Exposure

    6.9.1) DECONTAMINATION
    A) DERMAL DECONTAMINATION
    1) DECONTAMINATION: Remove contaminated clothing and wash exposed area thoroughly with soap and water for 10 to 15 minutes. A physician may need to examine the area if irritation or pain persists (Burgess et al, 1999).
    6.9.2) TREATMENT
    A) SKIN ABSORPTION
    1) Systemic poisoning has NOT been reported from routes of exposure other than ingestion (EPA, 1985). Carefully evaluate patients with dermal exposure for the presence of toxicity BEFORE undertaking any of the following treatments.
    B) SEIZURE
    1) SUMMARY
    a) Attempt initial control with a benzodiazepine (eg, diazepam, lorazepam). If seizures persist or recur, administer phenobarbital or propofol.
    b) Monitor for respiratory depression, hypotension, and dysrhythmias. Endotracheal intubation should be performed in patients with persistent seizures.
    c) Evaluate for hypoxia, electrolyte disturbances, and hypoglycemia (or, if immediate bedside glucose testing is not available, treat with intravenous dextrose).
    2) DIAZEPAM
    a) ADULT DOSE: Initially 5 to 10 mg IV, OR 0.15 mg/kg IV up to 10 mg per dose up to a rate of 5 mg/minute; may be repeated every 5 to 20 minutes as needed (Brophy et al, 2012; Prod Info diazepam IM, IV injection, 2008; Manno, 2003).
    b) PEDIATRIC DOSE: 0.1 to 0.5 mg/kg IV over 2 to 5 minutes; up to a maximum of 10 mg/dose. May repeat dose every 5 to 10 minutes as needed (Loddenkemper & Goodkin, 2011; Hegenbarth & American Academy of Pediatrics Committee on Drugs, 2008).
    c) Monitor for hypotension, respiratory depression, and the need for endotracheal intubation. Consider a second agent if seizures persist or recur after repeated doses of diazepam .
    3) NO INTRAVENOUS ACCESS
    a) DIAZEPAM may be given rectally or intramuscularly (Manno, 2003). RECTAL DOSE: CHILD: Greater than 12 years: 0.2 mg/kg; 6 to 11 years: 0.3 mg/kg; 2 to 5 years: 0.5 mg/kg (Brophy et al, 2012).
    b) MIDAZOLAM has been used intramuscularly and intranasally, particularly in children when intravenous access has not been established. ADULT DOSE: 0.2 mg/kg IM, up to a maximum dose of 10 mg (Brophy et al, 2012). PEDIATRIC DOSE: INTRAMUSCULAR: 0.2 mg/kg IM, up to a maximum dose of 7 mg (Chamberlain et al, 1997) OR 10 mg IM (weight greater than 40 kg); 5 mg IM (weight 13 to 40 kg); INTRANASAL: 0.2 to 0.5 mg/kg up to a maximum of 10 mg/dose (Loddenkemper & Goodkin, 2011; Brophy et al, 2012). BUCCAL midazolam, 10 mg, has been used in adolescents and older children (5-years-old or more) to control seizures when intravenous access was not established (Scott et al, 1999).
    4) LORAZEPAM
    a) MAXIMUM RATE: The rate of intravenous administration of lorazepam should not exceed 2 mg/min (Brophy et al, 2012; Prod Info lorazepam IM, IV injection, 2008).
    b) ADULT DOSE: 2 to 4 mg IV initially; repeat every 5 to 10 minutes as needed, if seizures persist (Manno, 2003; Brophy et al, 2012).
    c) PEDIATRIC DOSE: 0.05 to 0.1 mg/kg IV over 2 to 5 minutes, up to a maximum of 4 mg/dose; may repeat in 5 to 15 minutes as needed, if seizures continue (Brophy et al, 2012; Loddenkemper & Goodkin, 2011; Hegenbarth & American Academy of Pediatrics Committee on Drugs, 2008; Sreenath et al, 2009; Chin et al, 2008).
    5) PHENOBARBITAL
    a) ADULT LOADING DOSE: 20 mg/kg IV at an infusion rate of 50 to 100 mg/minute IV. An additional 5 to 10 mg/kg dose may be given 10 minutes after loading infusion if seizures persist or recur (Brophy et al, 2012).
    b) Patients receiving high doses will require endotracheal intubation and may require vasopressor support (Brophy et al, 2012).
    c) PEDIATRIC LOADING DOSE: 20 mg/kg may be given as single or divided application (2 mg/kg/minute in children weighing less than 40 kg up to 100 mg/min in children weighing greater than 40 kg). A plasma concentration of about 20 mg/L will be achieved by this dose (Loddenkemper & Goodkin, 2011).
    d) REPEAT PEDIATRIC DOSE: Repeat doses of 5 to 20 mg/kg may be given every 15 to 20 minutes if seizures persist, with cardiorespiratory monitoring (Loddenkemper & Goodkin, 2011).
    e) MONITOR: For hypotension, respiratory depression, and the need for endotracheal intubation (Loddenkemper & Goodkin, 2011; Manno, 2003).
    f) SERUM CONCENTRATION MONITORING: Monitor serum concentrations over the next 12 to 24 hours. Therapeutic serum concentrations of phenobarbital range from 10 to 40 mcg/mL, although the optimal plasma concentration for some individuals may vary outside this range (Hvidberg & Dam, 1976; Choonara & Rane, 1990; AMA Department of Drugs, 1992).
    6) OTHER AGENTS
    a) If seizures persist after phenobarbital, propofol or pentobarbital infusion, or neuromuscular paralysis with general anesthesia (isoflurane) and continuous EEG monitoring should be considered (Manno, 2003). Other anticonvulsants can be considered (eg, valproate sodium, levetiracetam, lacosamide, topiramate) if seizures persist or recur; however, there is very little data regarding their use in toxin induced seizures, controlled trials are not available to define the optimal dosage ranges for these agents in status epilepticus (Brophy et al, 2012):
    1) VALPROATE SODIUM: ADULT DOSE: An initial dose of 20 to 40 mg/kg IV, at a rate of 3 to 6 mg/kg/minute; may give an additional dose of 20 mg/kg 10 minutes after loading infusion. PEDIATRIC DOSE: 1.5 to 3 mg/kg/minute (Brophy et al, 2012).
    2) LEVETIRACETAM: ADULT DOSE: 1000 to 3000 mg IV, at a rate of 2 to 5 mg/kg/min IV. PEDIATRIC DOSE: 20 to 60 mg/kg IV (Brophy et al, 2012; Loddenkemper & Goodkin, 2011).
    3) LACOSAMIDE: ADULT DOSE: 200 to 400 mg IV; 200 mg IV over 15 minutes (Brophy et al, 2012). PEDIATRIC DOSE: In one study, median starting doses of 1.3 mg/kg/day and maintenance doses of 4.7 mg/kg/day were used in children 8 years and older (Loddenkemper & Goodkin, 2011).
    4) TOPIRAMATE: ADULT DOSE: 200 to 400 mg nasogastric/orally OR 300 to 1600 mg/day orally divided in 2 to 4 times daily (Brophy et al, 2012).
    C) NIACINAMIDE
    1) NOTE - NIACINAMIDE INJECTION IS NO LONGER COMMERCIALLY AVAILABLE
    a) IN THE UNITED STATES.
    2) NIACINAMIDE (not niacin or nicotinic acid): Has been demonstrated to be an effective antidote for streptozocin, alloxan, and pyriminil in the rat (Ganda et al, 1976; Rossini et al, 1975).
    a) In humans, little experience has been obtained using nicotinamide as an antidote. It appears to be most effective when given early after an ingestion, with less or no effect when given later. In one case where it was given 9 hours postingestion and another 14 hours postingestion, there was no appreciable effect (Pont et al, 1979).
    b) Nevertheless, the administration of large parenteral doses of niacinamide should be considered by the attending physician in those cases where Vacor or DLP-787 has been ingested.
    3) INTRAVENOUS DOSE - Initial dose ADULT: 500 milligrams intramuscularly or intravenously (slowly), follow with 100 to 200 milligrams intramuscularly or intravenously every 4 hours for up to 48 hours (Prod Info, 1976; (Howland et al, 1986). Adult dosage is 2 to 3 grams per day. CHILDREN - half the suggested adult dosage.
    4) MAXIMUM DOSE
    a) If signs of Vacor toxicity appear, niacinamide can be given every 2 hours but not to exceed a total of 3 grams each day for adults (Prod Info, 1976; (Miller et al, 1978).
    5) ORAL DOSE - Niacinamide 100 milligrams three to five times daily for two weeks can be administered. Treatment should be started as soon as possible after acute ingestion (Prod Info, 1976).
    6) LATE TREATMENT
    a) The experience with the initial use of niacinamide 3 to 4 days after the acute ingestion had taken place has not convincingly demonstrated improvement in the clinical course or outcome.
    7) Nicotinic acid has not been used in place of niacinamide. Animal studies have shown that nicotinic acid (niacin) has no effect on preventing diabetes, presumably due to inability to be taken up by pancreatic islet cells (Johnson et al, 1980).
    D) INSULIN (CLASS)
    1) Therapy for insulin dependent diabetes may be necessary.
    E) HYPOTENSIVE EPISODE
    1) Mineralocorticoids such as fludrocortisone (0.3 to 0.6 milligram/day) or deoxycorticosterone acetate (20 milligrams/day) have used with moderate success to treat the orthostatic hypotension.
    2) Dihydroergotamine was successfully used to treat hypotension refractory to steroids in one case (Benowitz et al, 1980), but was unsuccessful in another (Osterman et al, 1981).
    3) Oral ergotamine tartrate has been useful. However, the patient subsequently developed a bilateral toxic retinal vasculopathy, an extinguished electroretinogram, and a reduced dark-adaptation retinal sensitivity. These findings could have been attributed to Vacor toxicity, ergotamine toxicity, or a combination of the two (Mindel et al, 1981).
    4) Fluid loading, sodium loading, and elastic stockings are other measures that have been tried (Osterman et al, 1981; Benowitz et al, 1980).
    F) MONITORING OF PATIENT
    1) Monitor cardiac function and electrolyte balance closely.
    G) EXPERIMENTAL THERAPY
    1) OCULAR TOXICITY
    a) In rabbits, gentamicin 1 gram in 10 milliliters of water given orally 4 hours before, 1 hour before, and 4 hours after an oral dose of PNU 125 milligrams/kilogram was effective in preventing PNU-associated ocular toxicity (Mindel et al, 1988). Additional studies are needed to evaluate the efficacy of this treatment in humans.
    H) Treatment should include recommendations listed in the ORAL EXPOSURE section when appropriate.

Abstracts

Case Reports

    A) ADULT
    1) An adult male ingested six packets of Vacor (4.56 grams of PNU). Within 8 hours he had developed weakness, blurred vision, polyuria, and thirst. The patient was admitted and lavaged. By 22 hours postingestion his plasma glucose was 628 mg/dL which was treated with fluids and insulin.
    2) Over the next 3 days, urinary retention, urinary and fecal incontinence, severe muscle weakness, visual field constriction, and orthostatic hypotension developed. He was treated with niacinamide 500 mg IV every 6 hours (initiated 72 hours postingestion). The route was changed to oral on the 5th to the 11th hospital day.
    3) Orthostatic hypotension continued for 11 months and loss of bladder control for 7 months. The hypotension was treated with steroids and dihydroergotamine (Osterman et al, 1981).

Range Of Toxicity

Summary

    A) Minimal lethal or toxic dose is not well established in the literature. Death has been reported following ingestion of one-half of a single 39 gram package.
    B) The estimated acute toxic dose of Vacor is 5 mg/kg. However, severity of intoxication must be based on clinical and laboratory findings.

Minimum Lethal Exposure

    A) GENERAL/SUMMARY
    1) LDLO (ORAL) MAN - 22,286 micrograms/kilogram (RTECS , 2000)
    B) CASE REPORTS
    1) ADULT
    a) Ingestion of one-half of one 39-gram packet (2 percent) proved fatal in a human adult (Peoples & Maddy, 1979).
    2) PEDIATRIC
    a) A 7-year-old child was found dead the day after ingesting one packet of DLP-787 (2 percent RH-787)(Fretthold et al, 1980).

Maximum Tolerated Exposure

    A) CASE REPORTS
    1) Acute toxicity was reported in 4 cases. These persons each ingested one to three 39-gram packages of Vacor, each package containing 2 percent N-3-pyridylmethyl-N-'p-nitrophenyl urea (PNU). The acute toxic dose was calculated to be roughly 5 milligrams PNU/kilogram (Gallanosa et al, 1981).
    2) In 9 additional cases of adults who each ingested 39 grams of Vacor, two died. Of the seven suvivors, all developed chronic hypotension and permanent diabetes mellitus.
    3) PNU - The minimum dose reported to produce symptoms was 390 milligrams or 5.6 milligrams/kilogram (LeWitt, 1980).

Workplace Standards

    A) ACGIH TLV Values for CAS53558-25-1 (American Conference of Governmental Industrial Hygienists, 2010):
    1) Not Listed

    B) NIOSH REL and IDLH Values for CAS53558-25-1 (National Institute for Occupational Safety and Health, 2007):
    1) Not Listed

    C) Carcinogenicity Ratings for CAS53558-25-1 :
    1) ACGIH (American Conference of Governmental Industrial Hygienists, 2010): Not Listed
    2) EPA (U.S. Environmental Protection Agency, 2011): Not Listed
    3) IARC (International Agency for Research on Cancer (IARC), 2016; International Agency for Research on Cancer, 2015; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2010; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2010a; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2008; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2007; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2006; IARC, 2004): Not Listed
    4) NIOSH (National Institute for Occupational Safety and Health, 2007): Not Listed
    5) MAK (DFG, 2002): Not Listed
    6) NTP (U.S. Department of Health and Human Services, Public Health Service, National Toxicology Project ): Not Listed

    D) OSHA PEL Values for CAS53558-25-1 (U.S. Occupational Safety, and Health Administration (OSHA), 2010):
    1) Not Listed

Toxicity Information

    7.7.1) TOXICITY VALUES
    A) References: RTECS, 1992 Gallanosa et al, 1981
    1) LD50- (ORAL)MOUSE:
    a) 56,500 mcg/kg
    b) 80 mg/kg
    2) LD50- (ORAL)RAT:
    a) 6200 mcg/kg
    b) 4.5 mg/kg

Pharmacology Toxicology

Toxicologic Mechanism

    A) PNU may act as a nicotinamide antagonist in the synthesis of the coenzyme and its phosphate, and possibly cause an insulin deficient form of diabetes as a direct pancreatic beta-cell toxin similar in action to alloxan and streptozocin (Gallanosa et al, 1981). Islet cell surface antibodies reported in patients who had ingested Vacor(R) may have significance in associating the cause and effect.

Physicochemical

Molecular Weight

    A) 272.26

Animal Toxicology

Clinical Effects

    11.1.5) EQUINE/HORSE
    A) A horse who had ingested 0.25 to 0.5 kilogram Vacor developed severe muscle fasciculations, sweating, dilated pupils, and tachycardia (66 beats/minute) within 24 hours. Other signs reported in intoxicated horses include colic, hindlimb weakness, ataxia, and persistent inappetence (Russell & Monin, 1978).
    11.1.13) OTHER
    A) OTHER
    1) Vomiting, abdominal pain, depression, ataxia, decreased respiratory rate, visual problems, muscle tremors, and coma.

Treatment

    11.2.1) SUMMARY
    A) GENERAL TREATMENT
    1) Begin treatment immediately.
    2) Keep animal warm and do not handle unnecessarily.
    3) Sample vomitus, blood, urine, and feces for analysis.
    B) ANIMAL POISON CONTROL CENTERS
    1) ASPCA Animal Poison Control Center, An Allied Agency of the University of Illinois, 1717 S. Philo Rd, Suite 36, Urbana, IL 61802, website www.aspca.org/apcc
    2) It is an emergency telephone service which provides toxicology information to veterinarians, animal owners, universities, extension personnel and poison center staff for a fee. A veterinary toxicologist is available for consultation.
    3) The following 24-hour phone number is available: (888) 426-4435. A fee may apply. Please inquire with the poison center. The agency will make follow-up calls as needed in critical cases at no extra charge.
    11.2.2) LIFE SUPPORT
    A) GENERAL
    1) MAINTAIN VITAL FUNCTIONS: Secure airway, supply oxygen, and begin supportive fluid therapy if necessary.
    11.2.4) DECONTAMINATION
    A) GASTRIC DECONTAMINATION
    1) DOGS/CATS
    a) EMESIS AND LAVAGE - If within 2 hours of exposure: induce emesis with 1 to 2 milliliters/kilogram syrup of ipecac per os. Dogs may vomit more readily with 1 tablet (6 milligrams) apomorphine diluted in 3 to 5 milliliters water and instilled into the conjunctival sac or per os. Dogs may also be given apomorphine intravenously at 40 micrograms/kilogram. Do not use an emetic if the animal is hypoxic. In the absence of a gag reflex or if vomiting cannot be induced, place a cuffed endotracheal tube and begin gastric lavage. Pass large bore stomach tube and instill 5 to 10 milliliters/kilogram water or lavage solution, then aspirate. Repeat 10 times.
    b) ACTIVATED CHARCOAL - Administer activated charcoal. Dose: 2 grams/kilogram per os or via stomach tube. Avoid aspiration by proper restraint, careful technique, and if necessary tracheal intubation.
    c) CATHARTIC - Administer a dose of a saline cathartic such as magnesium or sodium sulfate (sodium sulfate dose is 1 gram/kilogram). If access to these agents is limited, give 5 to 15 milliliters magnesium oxide (Milk of Magnesia) per os for dilution.
    2) RUMINANTS/HORSES/SWINE
    a) EMESIS - Do not attempt to induce emesis in ruminants (cattle) or equids (horses).
    b) ACTIVATED CHARCOAL - Adult horses: administer 0.5 to 1 kilogram of activated charcoal in up to 1 gallon warm water via nasogastric tube. Neonates: administer 250 grams (one-half pound) activated charcoal in up to 2 quarts water. Adult cattle: administer 2 to 9 grams/ kilogram of activated charcoal in a slurry of 1 gram charcoal/3 to 5 milliliters warm water via stomach tube. Sheep may be given 0.5 kilogram charcoal in slurry.
    c) CATHARTIC - Administer an oral cathartic: mineral oil (small ruminants and swine, 60 to 200 milliliters; equids and cattle, 0.5 to 1 gallon); magnesium sulfate (ruminants and swine, 1 to 2 grams/kilogram; equine, 0.2 to 0.9 grams/kilogram); or milk of magnesia (small ruminants, up to 0.25 gram/kilogram in 1 to 3 gallons warm water; adult cattle up to 1 gram/kilogram in 1 to 3 gallons warm water or 2 to 4 boluses MgOH per os). Give these solutions via stomach tube and monitor for aspiration.
    11.2.5) TREATMENT
    A) DOGS/CATS
    1) MAINTAIN VITAL FUNCTIONS - as necessary.
    2) NICOTINAMIDE - (Nicotinic acid) can be given as repeated injections of 50 to 100 milligrams intramuscularly every 4 hours for up to 8 injections. Oral administration of 25 to 50 milligrams 3 to 5 times daily can subsequently be used for 7 to 10 days (Russell & Monin, 1978).
    3) MONITOR blood glucose levels and treat with insulin, or conversely, for hypoglycemia as needed.
    4) FLUIDS - Begin intravenous administration of lactated ringers or other solution at a rate of up to 60 milliliters/kilograms/hour. If packed cell volume is less than 25 percent or total protein is less than 3.5 grams/deciliter, give 10 to 20 milliliters/kilogram of the appropriate solution (whole blood, plasma, packed cells or dextran).
    5) HYPOGLYCEMIC SEIZURES rarely occur.
    a) DIAZEPAM - Dose of diazepam for DOGS & CATS is 0.5 milligram/kilogram intravenous bolus; may repeat dose every ten minutes for four total doses. Give slowly over 1 to 2 minutes.
    b) PHENOBARBITAL - Phenobarbital may be used as adjunct treatment at 5 to 30 milligrams/kilogram over 5 to 10 minutes intravenously.
    c) REFRACTORY SEIZURES - Consider anaesthesia or heavy sedation. Administer pentobarbital to DOGS & CATS at a dose of 3 to 15 milligrams/kilogram intravenously slowly to effect. May need to repeat in 4 to 8 hours. Be sure to protect the airway.
    6) SUPPORTIVE CARE - Antibiotics, temperature regulation, and other supportive care may be necessary for several days or weeks.
    B) RUMINANTS/HORSES/SWINE
    1) MAINTAIN VITAL FUNCTIONS - Secure airway, supply oxygen and begin supportive fluid therapy if necessary.
    2) NICOTINAMIDE - One report of successful treatment in an adult horse used a regimen of 2.2 milligrams/kilogram body weight intravenously, then injections of 1 gram each intramuscularly every 6 to 12 hours for three more days (Russell & Monin, 1978).
    3) MONITOR blood glucose levels and treat with insulin, or conversely, for hypoglycemia as needed.
    4) FLUIDS -
    a) HORSES - Administer electrolyte and fluid therapy as needed. Maintenance dose of intravenous isotonic fluids: 10 to 20 milliliters/kilogram per day. High dose for shock: 20 to 45 milliliters/kilogram/hour. Monitor for packed cell volume, adequate urine output and pulmonary edema. Goal is to maintain a urinary flow of 0.1 milliliter/kilogram/minute (2.4 liters/hour for an 880 pound horse).
    b) CATTLE - Administer electrolyte and fluid therapy, orally or parenterally as needed. Maintenance dose of intravenous isotonic fluids for calves and debilitated adult cattle: 140 milliliters/kilogram/day. Dose for rehydration: 50 to 100 milliliters/kilogram given over 4 to 6 hours.
    5) SUPPORTIVE CARE for several days or weeks may be necessary.

Continuing Care

    11.4.1) SUMMARY
    11.4.1.2) DECONTAMINATION/TREATMENT
    A) GENERAL TREATMENT
    1) Begin treatment immediately.
    2) Keep animal warm and do not handle unnecessarily.
    3) Sample vomitus, blood, urine, and feces for analysis.
    B) ANIMAL POISON CONTROL CENTERS
    1) ASPCA Animal Poison Control Center, An Allied Agency of the University of Illinois, 1717 S. Philo Rd, Suite 36, Urbana, IL 61802, website www.aspca.org/apcc
    2) It is an emergency telephone service which provides toxicology information to veterinarians, animal owners, universities, extension personnel and poison center staff for a fee. A veterinary toxicologist is available for consultation.
    3) The following 24-hour phone number is available: (888) 426-4435. A fee may apply. Please inquire with the poison center. The agency will make follow-up calls as needed in critical cases at no extra charge.
    11.4.2) DECONTAMINATION
    11.4.2.2) GASTRIC DECONTAMINATION
    A) GASTRIC DECONTAMINATION
    1) DOGS/CATS
    a) EMESIS AND LAVAGE - If within 2 hours of exposure: induce emesis with 1 to 2 milliliters/kilogram syrup of ipecac per os. Dogs may vomit more readily with 1 tablet (6 milligrams) apomorphine diluted in 3 to 5 milliliters water and instilled into the conjunctival sac or per os. Dogs may also be given apomorphine intravenously at 40 micrograms/kilogram. Do not use an emetic if the animal is hypoxic. In the absence of a gag reflex or if vomiting cannot be induced, place a cuffed endotracheal tube and begin gastric lavage. Pass large bore stomach tube and instill 5 to 10 milliliters/kilogram water or lavage solution, then aspirate. Repeat 10 times.
    b) ACTIVATED CHARCOAL - Administer activated charcoal. Dose: 2 grams/kilogram per os or via stomach tube. Avoid aspiration by proper restraint, careful technique, and if necessary tracheal intubation.
    c) CATHARTIC - Administer a dose of a saline cathartic such as magnesium or sodium sulfate (sodium sulfate dose is 1 gram/kilogram). If access to these agents is limited, give 5 to 15 milliliters magnesium oxide (Milk of Magnesia) per os for dilution.
    2) RUMINANTS/HORSES/SWINE
    a) EMESIS - Do not attempt to induce emesis in ruminants (cattle) or equids (horses).
    b) ACTIVATED CHARCOAL - Adult horses: administer 0.5 to 1 kilogram of activated charcoal in up to 1 gallon warm water via nasogastric tube. Neonates: administer 250 grams (one-half pound) activated charcoal in up to 2 quarts water. Adult cattle: administer 2 to 9 grams/ kilogram of activated charcoal in a slurry of 1 gram charcoal/3 to 5 milliliters warm water via stomach tube. Sheep may be given 0.5 kilogram charcoal in slurry.
    c) CATHARTIC - Administer an oral cathartic: mineral oil (small ruminants and swine, 60 to 200 milliliters; equids and cattle, 0.5 to 1 gallon); magnesium sulfate (ruminants and swine, 1 to 2 grams/kilogram; equine, 0.2 to 0.9 grams/kilogram); or milk of magnesia (small ruminants, up to 0.25 gram/kilogram in 1 to 3 gallons warm water; adult cattle up to 1 gram/kilogram in 1 to 3 gallons warm water or 2 to 4 boluses MgOH per os). Give these solutions via stomach tube and monitor for aspiration.

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) AMA Department of DrugsAMA Department of Drugs: AMA Evaluations Subscription, American Medical Association, Chicago, IL, 1992.
    14) Alaspaa AO, Kuisma MJ, Hoppu K, et al: Out-of-hospital administration of activated charcoal by emergency medical services. Ann Emerg Med 2005; 45:207-12.
    15) 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.
    16) Benowitz NL, Byrd R, & Schambelan M: Dihydroergotamine treatment for orthostatic hypotension from vacor rodenticide. Ann Intern Med 1980; 92:387-388.
    17) Brophy GM, Bell R, Claassen J, et al: Guidelines for the evaluation and management of status epilepticus. Neurocrit Care 2012; 17(1):3-23.
    18) Burgess JL, Kirk M, Borron SW, et al: Emergency department hazardous materials protocol for contaminated patients. Ann Emerg Med 1999; 34(2):205-212.
    19) Caravati EM, Knight HH, & Linscott MS: Esophageal laceration and charcoal mediastinum complicating gastric lavage. J Emerg Med 2001; 20:273-276.
    20) Chamberlain JM, Altieri MA, & Futterman C: A prospective, randomized study comparing intramuscular midazolam with intravenous diazepam for the treatment of seizures in children. Ped Emerg Care 1997; 13:92-94.
    21) Chin RF , Neville BG , Peckham C , et al: Treatment of community-onset, childhood convulsive status epilepticus: a prospective, population-based study. Lancet Neurol 2008; 7(8):696-703.
    22) Choonara IA & Rane A: Therapeutic drug monitoring of anticonvulsants state of the art. Clin Pharmacokinet 1990; 18:318-328.
    23) Chyka PA, Seger D, Krenzelok EP, et al: Position paper: Single-dose activated charcoal. Clin Toxicol (Phila) 2005; 43(2):61-87.
    24) 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.
    25) Dagnone D, Matsui D, & Rieder MJ: Assessment of the palatability of vehicles for activated charcoal in pediatric volunteers. Pediatr Emerg Care 2002; 18:19-21.
    26) EPA: EPA chemical profile on vacor, Environmental Protection Agency, Washington, DC, 1985.
    27) EPA: Recognition and management of pesticide poisonings, 2nd ed, US Environmental Protection Agency, Washington, DC, 1977.
    28) 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/.
    29) Elliot CG, Colby TV, & Kelly TM: Charcoal lung. Bronchiolitis obliterans after aspiration of activated charcoal. Chest 1989; 96:672-674.
    30) Esposti MD, Ngo A, & Myers MA: Inhibition of mitochondrial complex I may account for IDDM induced by intoxication with the rodenticide Vacor. Diabetes 1996; 45:1531-1534.
    31) FDA: Poison treatment drug product for over-the-counter human use; tentative final monograph. FDA: Fed Register 1985; 50:2244-2262.
    32) Fears WB: Letter to the editor. N Engl J Medicine 1980; 302:1147.
    33) Fretthold D, Sunshine I, & Udinsky JR: Postmortem findings for a Vacor poisoning case. Clin Toxicol 1980; 16:175-180.
    34) Gallanosa AG, Spyker DA, & Curnow RT: Diabetes mellitus associated with autonomic and peripheral neuropathy after vacor rodenticides: a review. Clin Toxicol 1981; 18:441-449.
    35) Ganda OP, Rossini AA, & Like AA: Studies on streptozotocin. Diabetes 1976; 25:595-603.
    36) Golej J, Boigner H, Burda G, et al: Severe respiratory failure following charcoal application in a toddler. Resuscitation 2001; 49:315-318.
    37) Graff GR, Stark J, & Berkenbosch JW: Chronic lung disease after activated charcoal aspiration. Pediatrics 2002; 109:959-961.
    38) Grant WM & Schuman JS: Toxicology of the Eye, 4th ed, Charles C Thomas, Springfield, IL, 1993.
    39) Guenther Skokan E, Junkins EP, & Corneli HM: Taste test: children rate flavoring agents used with activated charcoal. Arch Pediatr Adolesc Med 2001; 155:683-686.
    40) HSDB : Hazardous Substances Data Bank. National Library of Medicine. Bethesda, MD (Internet Version). Edition expires 1993; provided by Truven Health Analytics Inc., Greenwood Village, CO.
    41) HSDB : Hazardous Substances Data Bank. National Library of Medicine. Bethesda, MD (Internet Version). Edition expires 2000; provided by Truven Health Analytics Inc., Greenwood Village, CO.
    42) Harris CR & Filandrinos D: Accidental administration of activated charcoal into the lung: aspiration by proxy. Ann Emerg Med 1993; 22:1470-1473.
    43) Hayes WJ Jr & Laws ER Jr: Handbook of Pesticide Toxicology, Volume 2, Academic Press, Inc, San Diego, CA, 1991, pp 1283-1286.
    44) Hegenbarth MA & American Academy of Pediatrics Committee on Drugs: Preparing for pediatric emergencies: drugs to consider. Pediatrics 2008; 121(2):433-443.
    45) Howland MA, Weisman R, & Sauter D: Nonavailability of poison antidotes. N Engl J Med 1986; 314:927-930.
    46) Hvidberg EF & Dam M: Clinical pharmacokinetics of anticonvulsants. Clin Pharmacokinet 1976; 1:161.
    47) 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.
    48) 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.
    49) 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.
    50) 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.
    51) 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.
    52) 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.
    53) 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.
    54) 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.
    55) Johnson D, Kubic P, & Levitt C: Accidental ingestion of vacor rodenticide: the symptoms and sequelae in a 25 month old child. Am J Dis Child 1980; 134:161-164.
    56) Kenney RM, Michaels IAL, & Flomenbaum NE: Poisoning with N-3-pyridylmethyl-N'-p-nitrophenylurea (Vacor): Immunoperoxidase demonstration of beta-cell destruction. Arch Pathol Lab Med 1981; 105:367-370.
    57) LeWitt PA: The neurotoxicity of the rat poison Vacor: a clinical study of 12 cases. N Engl J Med 1980; 302:73-77.
    58) Litovitz T: The sniffing bar. Ann Emerg Med 1983; 12:332.
    59) Loddenkemper T & Goodkin HP: Treatment of Pediatric Status Epilepticus. Curr Treat Options Neurol 2011; Epub:Epub.
    60) Manno EM: New management strategies in the treatment of status epilepticus. Mayo Clin Proc 2003; 78(4):508-518.
    61) Miller LV, Stokes JD, & Silpipat C: Diabetics mellitis and autonomic dysfunction after vacor rodenticide ingestion. Diabetes Care 1978; 1:73.
    62) Mindel JS, Kharlamb AB, & Friedman AH: N-3-pyridylmethyl-N'-p-nitrophenylurea ocular toxicity in man and rabbits. Br J Ophthalmol 1988; 72:584-590.
    63) Mindel JS, Rubenstein AE, & Franklin B: Ocular ergotamine tartrate toxicity during treatment of Vacor-induced orthostatic hypotension. Am J Ophthalmol 1981; 92:492-496.
    64) Morgan DP: Recognition and Management of Pesticide Poisonings, 4th ed. US Environmental Protection Agency, EPA-540/9-88-001, US Government Printing Office, Washington, DC, 1989.
    65) NFPA: Fire Protection Guide to Hazardous Materials, 13th ed., National Fire Protection Association, Quincy, MA, 2002.
    66) 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.
    67) 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.
    68) 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.
    69) 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.
    70) Naradzay J & Barish RA: Approach to ophthalmologic emergencies. Med Clin North Am 2006; 90(2):305-328.
    71) 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.
    72) 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.
    73) 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.
    74) 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.
    75) 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.
    76) 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.
    77) 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.
    78) 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.
    79) 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.
    80) 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.
    81) 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.
    82) 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.
    83) 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.
    84) 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.
    85) 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.
    86) 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.
    87) 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.
    88) 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.
    89) 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.
    90) 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.
    91) 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.
    92) 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.
    93) 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.
    94) 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.
    95) 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.
    96) 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.
    97) 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.
    98) 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.
    99) 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.
    100) 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.
    101) 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.
    102) 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.
    103) 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.
    104) 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.
    105) 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.
    106) 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.
    107) 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.
    108) 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.
    109) 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.
    110) 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.
    111) 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.
    112) 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.
    113) 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.
    114) 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.
    115) 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.
    116) 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.
    117) 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.
    118) 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.
    119) 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.
    120) 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.
    121) 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.
    122) 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.
    123) 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.
    124) 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.
    125) 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.
    126) 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.
    127) 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.
    128) 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.
    129) 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.
    130) 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.
    131) 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.
    132) 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.
    133) 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.
    134) 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.
    135) 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.
    136) 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.
    137) 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.
    138) 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.
    139) 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.
    140) 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.
    141) 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.
    142) 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.
    143) 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.
    144) 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.
    145) National Heart,Lung,and Blood Institute: Expert panel report 3: guidelines for the diagnosis and management of asthma. National Heart,Lung,and Blood Institute. Bethesda, MD. 2007. Available from URL: http://www.nhlbi.nih.gov/guidelines/asthma/asthgdln.pdf.
    146) 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.
    147) National Research Council : Acute exposure guideline levels for selected airborne chemicals, 5, National Academies Press, Washington, DC, 2007.
    148) National Research Council: Acute exposure guideline levels for selected airborne chemicals, 6, National Academies Press, Washington, DC, 2008.
    149) National Research Council: Acute exposure guideline levels for selected airborne chemicals, 7, National Academies Press, Washington, DC, 2009.
    150) National Research Council: Acute exposure guideline levels for selected airborne chemicals, 8, National Academies Press, Washington, DC, 2010.
    151) None Listed: Position paper: cathartics. J Toxicol Clin Toxicol 2004; 42(3):243-253.
    152) Osterman J, Zmyslinski RW, & Hopkins CB: Full recovery from severe orthostatic hypotension after Vacor rodenticide ingestion. Arch Intern Med 1981; 141:1505-1507.
    153) Papasozomenos S: The rat poison Vacor. N Engl J Med 1980; 302:1146-1147.
    154) Peate WF: Work-related eye injuries and illnesses. Am Fam Physician 2007; 75(7):1017-1022.
    155) Peoples SA & Maddy KT: Poisoning of man and animals due to ingestion of the rodent poison, Vacor. Vet Hum Toxicol 1979; 21:266-268.
    156) Pollack MM, Dunbar BS, & Holbrook PR: Aspiration of activated charcoal and gastric contents. Ann Emerg Med 1981; 10:528-529.
    157) Pont A, Rubino JM, & Bishop D: Diabetes mellitus and neuropathy following Vacor ingestion in man. Arch Intern Med 1979; 139:185-187.
    158) Product Information: diazepam IM, IV injection, diazepam IM, IV injection. Hospira, Inc (per Manufacturer), Lake Forest, IL, 2008.
    159) Product Information: lorazepam IM, IV injection, lorazepam IM, IV injection. Akorn, Inc, Lake Forest, IL, 2008.
    160) Prosser PR & Karam JH: Diabetics mellitus following rodenticide ingestion in man. JAMA 1978; 239:1148.
    161) RTECS : Registry of Toxic Effects of Chemical Substances. National Institute for Occupational Safety and Health. Cincinnati, OH (Internet Version). Edition expires 1992; provided by Truven Health Analytics Inc., Greenwood Village, CO.
    162) RTECS : Registry of Toxic Effects of Chemical Substances. National Institute for Occupational Safety and Health. Cincinnati, OH (Internet Version). Edition expires 2000; provided by Truven Health Analytics Inc., Greenwood Village, CO.
    163) Rau NR, Nagaraj MV, Prakash PS, et al: Fatal pulmonary aspiration of oral activated charcoal. Br Med J 1988; 297:918-919.
    164) Rossini AA, Arcangeli MA, & Cahill GF: Studies on alloxan toxicity on the beta cell. Diabetes 1975; 24:516-522.
    165) Rubenstein AE, Ginsberg-Fellner F, & Korczyn AD: Chronic autonomic neuropathy due to rodenticide ingestion. Neurology 1980; 30:442.
    166) Russell SH & Monin T: Rodenticide toxicosis in a horse. J Am Vet Med Assoc 1978; 172:270-271.
    167) Scott R, Besag FMC, & Neville BGR: Buccal midazolam and rectal diazepam for treatment of prolonged seizures in childhood and adolescence: a randomized trial. Lancet 1999; 353:623-626.
    168) Spiller HA & Rogers GC: Evaluation of administration of activated charcoal in the home. Pediatrics 2002; 108:E100.
    169) Sreenath TG, Gupta P, Sharma KK, et al: Lorazepam versus diazepam-phenytoin combination in the treatment of convulsive status epilepticus in children: A randomized controlled trial. Eur J Paediatr Neurol 2009; Epub:Epub.
    170) Taniguchi H, Yamashiro Y, & Chung MY: Vacor inhibits insulin release from islets in vitro. J Endocrinol Invest 1989; 12:273-275.
    171) Thakore S & Murphy N: The potential role of prehospital administration of activated charcoal. Emerg Med J 2002; 19:63-65.
    172) 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.
    173) 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.
    174) 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-.
    175) 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.
    176) 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.
    177) 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.
    178) 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.
    179) 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-.
    180) U.S. Occupational Safety, and Health Administration (OSHA): Process safety management of highly hazardous chemicals. 29 CFR 2010 2010; 29(1910.119):348-.
    181) 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.
    182) Vale JA, Kulig K, American Academy of Clinical Toxicology, et al: Position paper: Gastric lavage. J Toxicol Clin Toxicol 2004; 42:933-943.
    183) Vale JA: Position Statement: gastric lavage. American Academy of Clinical Toxicology; European Association of Poisons Centres and Clinical Toxicologists. J Toxicol Clin Toxicol 1997; 35:711-719.
    184) Whittaker JW & Osteryoung J: Trace determination of Vacor rodenticide by pulse polarography. Anal Chem 1976; 48:1418-1420.