ACETONITRILE

Classification | Detailed evidence-based information

Substances Included Synonyms

Therapeutic Toxic Class

Specific Substances

1) Cyanomethane
2) Ethanenitrile
3) Ethyl nitrile
4) Methanecarbonitrile
5) Methyl Cyanide
6) CAS 75-05-8
7) CYANIDE, METHYL

1.2.1) MOLECULAR FORMULA
1) C2-H3-N

Available Forms Sources

1) Acetonitrile is a flammable, colorless, limpid liquid with an aromatic, ether-like odor, and it burns with a luminous flame. It is a highly polar liquid and is strongly reactive. It may be found as technical grade, nanograde, and spectophotometric grade (AAR, 1998; (ACGIH, 1991; Ashford, 1994; Budavari, 1996; ILO, 1998; Lewis, 1996; Lewis, 1997; Lewis, 1998; NFPA, 1994).
2) The following sculptured nail removers have been identified to contain acetonitrile (Caravati & Litovitz, 1988):

ACETONITRILE
PRODUCT	CONCENTRATION
*Ardell Instant Glue Remover (Ardell International, Inc)	98-100%
*Artificial Nail Tip and Glue Remover(OPI Products)	95% or more
Nailene Salon Quality Glue Remover(Pacific World Corporation)	Approx 84%
*Super Nail Glue Off (American International Industries)Super Nail Off	98-100%
*Super Nail Tip Off (American International Industries)
*Super Nail Wrap Off Instant Glue Dissolver(American International Industries)
*NOTE: This has been reformulated and no longer contains acetonitrile.

1) Acetonitrile is generated during ammoxidation, i.e. the reaction between propylene and ammonia. This reaction takes place during acrylonitrile production (Ashford, 1994).
2) Atmospheric releases of acetonitrile stem from incinerated polyacrylonitrile polymers, automobile exhausts, tobacco smoke, synthetic rubber manufacture, shale oil retorting, and turbine engines (Howard, 1993).

1) Acetonitrile is one of the more important organic nitriles in industrial use. It is used as a solvent in hydrocarbon extraction processes (especially for butadiene extraction). It is used as a starting material in the organic synthesis of acetophenone, alpha-naphthaleneacetic acid, thiamine, and acetamide. It is also used to remove tars, phenols, and coloring matter from petroleum hydrocarbons that are insoluble in acetonitrile, and in the extraction of fatty acids from fish liver oils and other animal and vegetable oils. Other uses include pharmaceutical manufacturing. Acetonitrile can be used as a polar solvent anytime a solvent with a rather high dielectric constant is required. (ACGIH, 1991; Ashford, 1994; Budavari, 1996; Clayton & Clayton, 1994; ILO, 1998; Lewis, 1997).
2) It is one of the ingredients of glue removers used for artificial fingernails (Basel and Cravey, 1995).

Overview

Life Support

Clinical Effects

0.2.1)

A) USES: Acetonitrile (CH3CN) is a by-product of acrylonitrile manufacture. It is a liquid with an ether-like odor. Acetonitrile is a volatile, highly polar solvent used to extract fatty acids and animal and vegetable oils. It is used in the petrochemical industry in extractive distillation based on its selective miscibility with water and organic compounds. It is used as a solvent for spinning synthetic fibers and in casting and molding plastics. In laboratories, it is widely used in high-performance liquid chromatographic (HPLC) analysis and as a solvent for DNA synthesis and peptide sequencing. It may be encountered in the home in high concentrations in certain glues and artificial nail removers.
B) TOXICOLOGY: Acetonitrile is readily absorbed in the lungs, skin, and gastrointestinal tract. All three routes have been implicated in human toxicity. Acetonitrile is metabolized in the liver in the cytochrome P450 system to cyanide. The liberation of cyanide accounts for the toxicity of acetonitrile. This metabolism also accounts for the delay in toxicity after exposure. Typically, toxic effects begin 2 to 13 hours after exposure as cyanide accumulates in the body.
C) EPIDEMIOLOGY: Exposures are uncommon, but deaths have been reported. Toxicity can occur after ingestion, inhalation, or dermal exposure. Occupational/industrial outbreaks have occurred and typically involve inhalational exposure. While acetonitrile containing glues and artificial nail removers have been banned by the European Economic Area since 2000, they may still be available in North America.
D) WITH POISONING/EXPOSURE

1) MILD TO MODERATE POISONING: Headache, nausea, vomiting, and dizziness may develop.
2) SEVERE POISONING: Severe manifestations may take 2 to 13 hours to develop and are due to cyanide accumulation. Vomiting usually precedes severe toxicity by at least 2 hours. Hypotension, acidosis, altered mental status, coma, Kussmaul respirations, respiratory failure, seizures, and cardiovascular collapse may occur. Gastrointestinal symptoms may also be present, especially with ingestions. Elevated anion gap metabolic acidosis and lactic acidosis are common after ingestion.

0.2.20)

A) No human reproductive studies have been found. Animal studies have shown birth defects following exposure to acetonitrile from various routes.

0.2.21)

A) At the time of this review, no studies were found on the possible carcinogenic activity of acetonitrile in humans.

Laboratory Monitoring

Treatment Overview

0.4.2)

A) MANAGEMENT OF MILD TO MODERATE TOXICITY

1) Treatment is symptomatic and supportive. Administer intravenous fluids and monitor carefully for evidence of more severe toxicity.

B) MANAGEMENT OF SEVERE TOXICITY

1) Treatment should include volume expansion, pressors as needed for hypotension, ventilatory support, and hydroxocobalamin or the cyanide antidote kit. Seizures should be considered an indication of severe toxicity and should be treated with benzodiazepines and hydroxocobalamin. Consider neurologic consult and continuous EEG monitoring for the sedated, chemically paralyzed, and intubated patient. Several patients with unrecognized acetonitrile exposure and cyanide toxicity have survived with ICU level supportive care (eg, volume expansion, pressor support, endotracheal intubation, and mechanical ventilation) in the absence of antidote administration.

C) DECONTAMINATION

1) PREHOSPITAL: Prehospital gastrointestinal decontamination is not recommended due to the potential for seizures and profound depression and subsequent aspiration risk.
2) HOSPITAL: Activated charcoal may be of benefit early after ingestion exposures. However, these patients are at risk for aspiration due to the potential for seizures and profound CNS depression. Activated charcoal should be reserved for the awake, alert, non-seizing patient, or the intubated patient. Consider orogastric lavage for patients with very recent ingestions who are alert and can protect the airway or are intubated.

D) AIRWAY MANAGEMENT

1) Ensure adequate ventilation and perform endotracheal intubation early in patients with severe CNS depression.

E) CYANIDE ANTIDOTE

1) A cyanide antidote, either hydroxocobalamin or the sodium nitrite/sodium thiosulfate kit, should be administered to symptomatic patients.

F) HYDROXOCOBALAMIN

1) Hydroxocobalamin should be given if any laboratory or clinical signs or symptoms of cyanide toxicity develop. ADULT: Administer 5 g (two 2.5 g vials, each reconstituted with 100 mL sterile 0.9% saline) as an IV infusion over 15 minutes. For severe poisoning, a second dose of 5 g may be infused intravenously over 15 minutes to 2 hours, depending on the patient's condition. PEDIATRIC: Limited experience; a dose of 70 mg/kg has been used in pediatric patients.

G) CYANIDE ANTIDOTE KIT

1) An alternative, a sodium nitrite/sodium thiosulfate kit, is administered as follows: SODIUM NITRITE: ADULT: 300 mg (10 mL of 3% solution) IV at a rate of 2.5 to 5 mL/min; PEDIATRIC: (with normal hemoglobin concentration) 0.2 mL/kg of a 3% solution (6 mg/kg) IV at a rate of 2.5 to 5 mL/min, not to exceed 10 mL (300 mg). A second dose, one-half of the first dose, may be administered 30 minutes later if there is inadequate clinical response. SODIUM THIOSULFATE: Follow sodium nitrite with IV sodium thiosulfate. ADULT: 50 mL (12.5 g) of a 25% solution; PEDIATRIC: 1 mL/kg of a 25% solution (250 mg/kg), not to exceed 50 mL (12.5 g) total dose. A second dose, one-half of the first dose, may be administered if signs of cyanide toxicity reappear. ALTERNATE ANTIDOTES: Kelocyanor(R) (dicobalt-EDTA) and 4-DMAP (4-dimethylaminophenol) are among the cyanide antidotes in clinical use outside the US.

H) ENHANCED ELIMINATION

1) Antidotes increase elimination, however, the role of hemodialysis is uncertain.

I) PATIENT DISPOSITION

1) HOME CRITERIA: Home observation should not be considered as even small volume exposures in initially asymptomatic patients have resulted in severe toxicity. Patients with inhalational exposures exposed in an industrial setting should seek health care as the amount and duration of exposure can be difficult to quantify.
2) OBSERVATION CRITERIA: All patients with potential acetonitrile exposures should be referred to a healthcare facility.
3) ADMISSION CRITERIA: Patients should be admitted to an ICU setting and monitored for at least 24 hours as toxicity is expected to be delayed while cyanide is being produced via hepatic metabolism.
4) CONSULT CRITERIA: Consult a medical toxicologist or poison center for any patient with significant toxicity or in whom the diagnosis is unclear.

J) PITFALLS

1) Most poor outcomes are associated with a failure to recognize an acetonitrile containing product or failure to recognize the expected 2 to 13 hour delay in toxicity.

K) TOXICOKINETICS

1) Cyanide concentrations in the serum typically become elevated 2 to 13 hours after exposure. The duration of toxicity is difficult to assess and may be prolonged by delay to care and worsening clinical condition rather than metabolic variation. Half-life of acetonitrile is 32 to 36 hours. Half-life of cyanide in cases of acetonitrile poisoning has been 15 to 44 hours.

L) DIFFERENTIAL DIAGNOSIS

1) Acetone exposure, methemoglobinemia, carbon monoxide exposure, cyanide from another source.

0.4.3)

A) 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.

Range Of Toxicity

Clinical Effects

Summary Of Exposure

Heent

3.4.2)

A) WITH POISONING/EXPOSURE

1) FLUSHING: One of two patients exposed to an airborne concentration of 160 ppm for 4 hours developed facial flushing 2 hours after exposure (ACGIH, 1980; Pozzani et al, 1959).

Cardiovascular

3.5.2)

A) CONDUCTION DISORDER OF THE HEART

1) WITH POISONING/EXPOSURE

a) Tachycardia, bradycardia, palpitations, and cardiac arrest have been reported in cases of acetonitrile poisoning following inhalation exposure (ITI, 1988; (Dequidt et al, 1974; Amdur, 1959) and following acetonitrile ingestion (Mueller & Borland, 1997; Boggild et al, 1990a; Caravati & Litovitz, 1988).

B) HYPOTENSIVE EPISODE

1) WITH POISONING/EXPOSURE

a) Hypotension has been reported following inhalation exposure (Amdur, 1959; Dequidt et al, 1974) and following acetonitrile ingestion (Mueller & Borland, 1997; Boggild et al, 1990; Caravati & Litovitz, 1988).

Respiratory

3.6.2)

A) CHEST PAIN

1) WITH POISONING/EXPOSURE

a) CHEST TIGHTNESS: Inhalation exposure to an airborne concentration of 40 ppm for 4 hours produced no immediate effect in human volunteers, but 1 individual developed chest tightness and a "cooling" sensation similar to that experienced when inhaling menthol. Inhalation of an airborne concentration of 80 ppm for 4 hours caused no clinical effects, and 1 of 2 subjects exposed to 160 ppm developed slight bronchial tightness 5 hours after exposure (Pozzani et al, 1959).

B) HYPERVENTILATION

1) WITH POISONING/EXPOSURE

a) HYPERPNEA has been reported (ITI, 1988) (Kurt et al, 1991; Turchen et al, 1991a).

3.6.3)

A) ANIMAL STUDIES

1) PULMONARY HEMORRHAGE

a) Pulmonary hemorrhage was seen in experimental animals fatally poisoned by inhalation (Proctor & Hughes, 1978). Pulmonary inflammation was seen in rats exposed to an airborne concentration of 665 ppm for 7 hours daily.

Neurologic

3.7.2)

A) COMA

1) WITH POISONING/EXPOSURE

a) INGESTION: Coma has been reported after ingestion of as little as 5 mL to 10 mL by a child, with a delayed onset of 12 hours (Kurt et al, 1991). Coma has been reported in 2 adults following ingestion of an estimated amount of 40 mL and 25 grams acetonitrile, with a delayed onset of 3 hours and 11 hours, respectively (Mueller & Borland, 1997; Jaeger et al, 1977).
b) INHALATION: Dizziness leading to coma has been reported (Dequidt et al, 1974; Amdur, 1959). Dizziness is also a symptom of chronic exposure (ITI, 1988).

B) SEIZURE

1) WITH POISONING/EXPOSURE

a) INGESTION: Seizures have been reported after ingestion of 5 to 10 mL by a child with a delayed onset of 12 hours (Kurt et al, 1991), 60 mL by an adult with a delayed onset of 11 hours (Turchen et al, 1991a), 25 grams by an adult with a delayed onset of 11 hours (Mueller & Borland, 1997), and an unknown amount by an adult with a delayed onset of 26 hours (Boggild et al, 1990).
b) INHALATION: Seizures have been reported following accidental inhalation exposure to acetonitrile (Amdur, 1959; Dequidt et al, 1974; ACGIH, 1980).
c) DELAYED ONSET SEIZURES: A 22-year-old woman died after presenting with cardiovascular collapse and severe metabolic acidosis at the 24th hour and seizures at the 42nd hour following ingestion of acetone and acetonitrile (Boggild et al, 1990).

C) AT RISK - FINDING

1) A history of fainting spells or convulsive disorders might present an added risk to persons working with toxic nitriles (HSDB , 1991).

Gastrointestinal

3.8.2)

A) NAUSEA AND VOMITING

1) WITH POISONING/EXPOSURE

a) Nausea and/or vomiting may follow acute inhalation or ingestion exposure (Caravati & Litovitz, 1988; Mueller & Borland, 1997; Turchen et al, 1991; Kurt et al, 1991; Geller et al, 1991; Losek et al, 1991). Nausea and/or vomiting have been observed to precede serious toxicity by several hours in most cases of ingestion. Vomiting may be bloody (Proctor & Hughes, 1978).

B) LOSS OF APPETITE

1) WITH POISONING/EXPOSURE

a) Anorexia may be noted in patients exposed chronically (ITI, 1988).

Acid-Base

3.11.2)

A) METABOLIC ACIDOSIS

1) WITH POISONING/EXPOSURE

a) Metabolic acidosis has been reported after ingestion of acetonitrile (Mueller & Borland, 1997; Kurt et al, 1991; Boggild et al, 1990; Turchen et al, 1991; Caravati & Litovitz, 1988).
b) CASE REPORT: Severe hypoxia and profound metabolic acidosis were reported in an adult following inhalation exposure to acetonitrile (Zavotsky et al, 2004).
c) Contributing factors to metabolic acidosis may also include hypotension, seizures, and cardiac arrest.

B) LACTIC ACIDOSIS

1) WITH POISONING/EXPOSURE

a) INGESTION: Lactic acidosis has been reported following ingestion (Boggild et al, 1990; Losek et al, 1991).
b) CASE REPORT: Severe lactic acidosis was reported in a 30-year-old lab technician who ingested a chemical later identified as acetonitrile. Following 3 doses of hydroxocobalamin and sodium thiosulfate and 400 mg disulfiram orally, the patient completely recovered with resolution of his acidosis (De Paepe et al, 2016).

Dermatologic

3.14.2)

A) DERMATITIS

1) WITH POISONING/EXPOSURE

a) Acetonitrile may cause skin irritation (Budavari, 1989). Chronic exposure may produce maculopapular vesicular dermatitis (ITI, 1988).

3.14.3)

A) ANIMAL STUDIES

1) IRRITATION

a) This liquid, when spilled on the belly of a rabbit, caused faint erythema of short duration (Proctor & Hughes, 1975).

2) PERCUTANEOUS ABSORPTION

a) SYSTEMIC POISONING: Dermal exposure has caused systemic poisoning in experimental animals (Pozzani et al, 1959).

Reproductive

3.20.1)

A) No human reproductive studies have been found. Animal studies have shown birth defects following exposure to acetonitrile from various routes.

3.20.2)

A) ANIMAL STUDIES

1) SKELETAL MALFORMATION

a) Pregnant hamsters exposed by either inhalation to airborne concentrations of 5,000 or 8,000 ppm or given 100 to 400 mg/kg oral or intraperitoneal doses of acetonitrile delivered offspring with severe axial skeletal disorders (Willhite, 1983). Injections of sodium thiosulfate antagonized the teratogenic effects (Willhite, 1983).

2) Elevated cyanide and thiocyanate levels were found in all tissue studied 2.5 hours after oral or intraperitoneal dosing, suggesting that in vivo liberation of cyanide from acetonitrile was responsible for the observed teratogenic effects (Willhite, 1983). Cyanide is an unconfirmed human reproductive hazard because it has been linked with congenital cretinism and goiter in populations subsisting on diets high in cyanogenic glycosides (eg, cassava). See "CYANIDE" management for further information.

3.20.3)

A) ANIMAL STUDIES

1) Inhalation of acetonitrile by pregnant animals may produce malformations in the offspring such as axial skeletal disorders, at maternally toxic levels (Hashimoto, 1991).
2) Acetonitrile was embryotoxic at high doses which were also toxic to the dams in rats, but did not cause birth defects (Johannsen, 1986).

Carcinogenicity

3.21.1)

A) IARC Carcinogenicity Ratings for CAS75-05-8 (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)

A) At the time of this review, no studies were found on the possible carcinogenic activity of acetonitrile in humans.

Genotoxicity

Laboratory Monitoring

Monitoring Parameters Levels

4.1.1)

A) Monitor vital signs and mental status.
B) Monitor serum electrolytes, renal function, and lactate concentration.
C) Institute continuous cardiac monitoring and obtain an ECG.
D) Cyanide concentrations in blood and tissue typically become elevated more than 2 hours post-exposure.
E) Serum acetonitrile concentrations may obtained from reference laboratories to confirm exposure but are not useful to guide therapy.
F) Treatment and disposition decisions should be based on reported exposure and symptoms; do not delay care waiting for serum acetonitrile or cyanide concentrations.

4.1.2)

A) BLOOD/SERUM CHEMISTRY

1) Patients exposed to 40 to 160 ppm for 4 hours did not have increased whole blood cyanide levels, but did have mildly elevated thiocyanate levels (Pozzani et al, 1959). Thiocyanate levels were inconsistently elevated and no conclusions could be drawn (ACGIH, 1980).

a) Because of this data and variability in experimental animal studies, no reliance should be placed on cyanide or thiocyanate levels. Cyanide ion was detected in a fatality due to an unknown, but high, concentration of acetonitrile.

2) A whole blood cyanide level of 6 mcg/mL (231 mcmol/L) was reported at 12 hours postexposure in a 2-year-old child who was found with an open bottle of acetonitrile-containing cosmetic (Caravati & Litovitz, 1988).
3) Monitor serum electrolytes, renal function, and lactate concentration.

4.1.4)

A) OTHER

1) ECG

a) Institute continuous cardiac monitoring and obtain an ECG.

2) MONITORING

a) Monitor vital signs and mental status.

Methods

1) In vitro, cyanide was NOT generated from acetonitrile added to whole blood during whole blood cyanide assays using the Conway microdiffusion technique (detection limit 0.01 mcg/mL), thus arguing strongly against the hypothesis that elevated whole blood cyanide levels measured following acetonitrile exposure might be artifactual (Kirk et al, 1989).

Treatment

Life Support

Patient Disposition

6.3.1)

6.3.1.1) ADMISSION CRITERIA/ORAL

A) Patients should be admitted to an ICU setting and monitored for at least 24 hours as toxicity is expected to be delayed while cyanide is being produced via hepatic metabolism.

6.3.1.2) HOME CRITERIA/ORAL

A) Home observation should not be considered as even small volume exposures in initially asymptomatic patients have resulted in severe toxicity. Patients with inhalational exposures exposed in an industrial setting should seek health care as the amount and duration of exposure can be difficult to quantify.

6.3.1.3) CONSULT CRITERIA/ORAL

A) Consult a medical toxicologist or poison center for any patient with significant toxicity or in whom the diagnosis is unclear.

6.3.1.5) OBSERVATION CRITERIA/ORAL

A) All patients with potential acetonitrile exposures should be referred to a healthcare facility.

Monitoring

Oral Exposure

6.5.1)

A) Prehospital gastrointestinal decontamination is not recommended due to the potential for seizures and profound CNS depression and subsequent aspiration risk.

6.5.2)

A) SUMMARY

1) In symptomatic patients, skip these steps until other major emergency measures, including use of the Cyanide Antidote Kit or alternative specific cyanide antidote and other life support measures, have been instituted.

B) ACTIVATED CHARCOAL

1) The usefulness of activated charcoal may be questionable, but one gram of activated charcoal may absorb 35 mg of potassium cyanide (Anderson, 1946). As acetonitrile must to be converted to cyanide by hepatic metabolism, activated charcoal may play a larger role than with cyanide alone.
2) 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.

3) 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)

A) MONITORING OF PATIENT

1) Monitor vital signs and mental status.
2) Monitor serum electrolytes, renal function, and lactate concentration.
3) Institute continuous cardiac monitoring and obtain an ECG.
4) Cyanide concentrations in blood and tissue typically become elevated more than 2 hours post exposure.
5) Serum acetonitrile concentrations may obtained from reference laboratories to confirm exposure but are not useful to guide therapy.
6) Treatment and disposition decisions should be based on reported exposure and symptoms; do not delay care waiting for serum acetonitrile or cyanide concentrations.
7) INTERPRETATION OF LABORATORY VALUES

a) The following set of screening laboratory values suggest poisoning with an agent that inhibits oxidative phosphorylation (ie, cyanide, hydrogen sulfide) (Hall & Rumack, 1986).

1) Arterial pO2: Usually relatively normal until the stage of apnea. Usually remains relatively normal until terminal stages of the poisoning if supplemental oxygen and assisted ventilation are provided.
2) Serum electrolytes: Elevated anion gap (Na - (Cl + CO2)) (normals 7 +/- 4 milliequivalents/liter (7 +/- 4 millimoles/liter)) is noted because of the presence of unmeasured organic anions (usually lactate) (Goldfrank, 1998)
3) Serum Lactate: Elevated (normals 0.6 to 1.8 milliequivalents/liter) (0.6 to 1.8 millimoles/liter) due to anaerobic metabolism with excessive production of lactic acid. Elevated serum lactate levels may correlate best with the presence of cyanide poisoning.
4) Arterio-Central Venous Measured %O2 Saturation Difference - Due to cellular inability to extract and use oxygen, more is present on the venous side. The MEASURED values of arterial and central venous %O2 saturation approach each other with MEASURED central venous %O2 saturation greater than 70%.
5) Arteriolization of venous blood gases (elevated venous pO2 or measured venous %O2 saturation) may serve as an early clue in the diagnosis of cyanide poisoning (Hall & Rumack, 1986; Johnson & Mellors, 1988).

B) OXYGEN

1) Administer 100% humidified supplemental oxygen with assisted ventilation as required.

a) Experimental animal data suggest that supplemental oxygen as adjunctive treatment for cyanide poisoning may increase the overall antidotal efficacy of sodium nitrite and sodium thiosulfate (Burrow et al, 1977; Way et al, 1966; Sheehy et al, 1968).
b) The Undersea Medical Society has classified cyanide in its Category 1 for hyperbaric oxygen therapy (HBO) (approved for third party reimbursement and known effective as treatment) (Myers & Schnitzer, 1984). This is in contrast to the existing literature which indicates that the role of HBO as an adjunct to specific antidotes has not been clearly established.
c) Experimental animal data suggest that hyperbaric oxygen may attenuate cyanide toxicity (Ivanov, 1959) (Skene et al, 1966; Takano et al, 1980), but not all studies have shown hyperbaric oxygen to improve outcome (Way et al, 1972).
d) Reported results of HBO in clinical cases of cyanide poisoning refractory to standard antidotal treatment (sodium nitrite and sodium thiosulfate) have been equivocal (Carden, 1970; Trapp, 1970; Litovitz et al, 1983) (Trapp et al, 1983) (Hart et al, 1985) Davis et al, 1988; Rosenberg et al, 1989; Feldman et al, 1990; Scolnick et al, 1993; Goodhart, 1994).
e) The role of HBO as an adjunct to specific antidotes has not been clearly established. Hyperbaric oxygen may be an adjunct to be considered in patients who are not responding to supportive care and specific antidotal therapy, and for those patients poisoned by both cyanide and carbon monoxide (Hart et al, 1985).

C) FLUID/ELECTROLYTE BALANCE REGULATION

1) Establish secure large bore IV line; consider placing at least two intravenous lines.

D) CYANIDE ANTIDOTE

1) A cyanide antidote, either hydroxocobalamin or the sodium nitrite/sodium thiosulfate kit, should be administered to patients with symptomatic poisoning.
2) HYDROXOCOBALAMIN - CYANOKIT(R)

a) ADULT DOSE: 5 g (two 2.5 g vials each reconstituted with 100 mL sterile 0.9% saline) administered as an intravenous infusion over 15 minutes. For severe poisoning, a second dose of 5 g may be infused intravenously over 15 minutes to 2 hours, depending on the patient's condition (Prod Info CYANOKIT(R) 2.5g IV injection, 2006).
b) PEDIATRIC DOSE: A dose of 70 mg/kg has been used in pediatric patients, based on limited post-marketing experience outside the US (Prod Info CYANOKIT(R) 2.5g IV injection, 2006).
c) INDICATIONS: Known or suspected cyanide poisoning.
d) ADVERSE EFFECTS: Transient hypertension, allergic reactions (including anaphylaxis), nausea, headache, rash. Hydroxocobalamin's deep red color causes red-colored urine in all patients, and erythema of the skin in most (Prod Info CYANOKIT(R) 2.5g IV injection, 2006).
e) LABORATORY INTERFERENCE: Because of its' color, hydroxocobalamin interferes with colorimetric determination of various laboratory parameters. It may artificially increase serum creatinine, bilirubin, triglycerides, cholesterol, total protein, glucose, albumin , alkaline phosphatase and hemoglobin. It may artificially decrease serum ALT and amylase. It may artificially increase urinary pH, glucose, protein, erythrocytes, leukocytes, ketones, bilirubin, urobilinogen, and nitrate (Prod Info CYANOKIT(R) 2.5g IV injection, 2006).
f) HEMODIALYSIS INTERFERENCE: Dialysis machines have a spectrophotometric safety measure that can shut down after detecting blood leaking across the dialysis membrane. Hydroxocobalamin has a deep red color and can permeate the dialysis membrane, coloring the dialysate and causing the hemodialysis machine to shut down erroneously. In one case report, a patient with cyanide poisoning underwent dialysis after receiving 5 g of IV hydroxocobalamin because of refractory acidemia, reduced kidney function and hyperkalemia. A blood leak alarm caused the dialysis machine to shut down erroneously, delaying therapy, and resulting in the death of the patient (Stellpflug et al, 2013).

3) CYANIDE ANTIDOTE KIT

a) OBTAIN AND PREPARE for administration a CYANIDE ANTIDOTE KIT.
b) Antidotes should be administered to patients who are significantly symptomatic with unstable vital signs, metabolic acidosis, impaired consciousness, seizures, coma, or cardiorespiratory compromise.
c) In instances when acetonitrile ingestion was recognized and treatment with specific cyanide antidotes was initiated within a few hours, patient survival was increased (Swanson et al, 1993). It has been suggested that intravenous sodium thiosulfate and perhaps nitrites be administered to symptomatic patients who have ingested acetonitrile prior to the onset of acidosis (Mueller et al, 1996).

E) SODIUM NITRITE

1) INDICATIONS

a) Sodium nitrite should be given initially and administered as soon as vascular access is established. A repeat dose of nitrite, in combination with thiosulfate, was used in one case where clinical deterioration occurred 34.5 hours after ingestion, resulting in hypotension. A subsequent clinical deterioration was treated with thiosulfate alone with an equivalent response (Turchen et al, 1991a).

1) Sodium thiosulfate can be given without sodium nitrite in patients who deteriorate after the initial administration of the antidote kit, provided that the patient is stable and the clinical condition does not warrant more aggressive therapy.

b) INDICATION

1) Sodium nitrite should be given initially and administered as soon as vascular access is established.
2) Further administration of sodium nitrite is dictated only by the clinical situation, provided no significant complications (hypotension, excessive methemoglobinemia) are present. Use with caution if carbon monoxide poisoning is also suspected.
3) The goal of nitrite therapy is to achieve a methemoglobin level of 20% to 30%. This level is not based on clinical data, but represents the tolerated concentration without significant adverse symptoms from methemoglobin in an otherwise healthy individual. Clinical response has been reported to occur with methemoglobin levels in the range of 3.6% to 9.2% (DiNapoli et al, 1989; Johnson et al, 1989a; Johnson & Mellors, 1988).

c) ADULT DOSE

1) 10 mL of a 3% solution (300 mg) administered intravenously at a rate of 2.5 to 5 mL/minute (Prod Info NITHIODOTE intravenous injection solution, 2011). Frequent blood pressure monitoring must accompany sodium nitrite injection and the rate slowed if hypotension occurs.
2) If there is inadequate clinical response, an additional dose of sodium nitrite at half the amount of the initial dose may be administered 30 minutes following the first dose (Prod Info NITHIODOTE intravenous injection solution, 2011).

d) PEDIATRIC DOSE

1) The recommended pediatric sodium nitrite dose is 0.2 mL/kg of a 3% solution (6 mg/kg) administered intravenously at a rate of 2.5 to 5 mL/minute, not to exceed 10 mL (300 mg) (Prod Info NITHIODOTE intravenous injection solution, 2011).
2) If there is inadequate clinical response, an additional dose of sodium nitrite at half the amount of the initial dose may be administered 30 minutes following the first dose (Prod Info NITHIODOTE intravenous injection solution, 2011; Berlin, 1970).
3) PRESENCE OF ANEMIA: If there is a reason to suspect the presence of anemia, the following initial sodium nitrite doses should be given, depending on the child's hemoglobin (sodium nitrite should not exceed the doses listed below; fatal methemoglobinemia may result) (Berlin, 1970):

a) Hemoglobin: 8 g/dL - Initial 3% sodium nitrite dose: 0.22 mL/kg (6.6 mg/kg)
b) Hemoglobin: 10 g/dL - Initial 3% sodium nitrite dose: 0.27 mL/kg (8.7 mg/kg)
c) Hemoglobin: 12 g/dL (average child) - Initial 3% sodium nitrite dose: 0.33 mL/kg (10 mg/kg)
d) Hemoglobin: 14 g/dL - Initial 3% sodium nitrite dose: 0.39 mL/kg (11.6 mg/kg)

F) SODIUM THIOSULFATE

1) Sodium thiosulfate is the second component of the cyanide antidote kit. It is supplied as 50 mL of a 25% solution and it is administered intravenously. There are no adverse reactions to thiosulfate itself. The pediatric dose is adjusted for weight and not hemoglobin concentration.
2) Sodium thiosulfate supplies sulfur for the rhodanese reaction, and is recommended after sodium nitrite, hydroxocobalamin, or 4-DMAP (4-dimethylaminophenol) administration (Marrs, 1988; Hall & Rumack, 1987).
3) DOSE

a) Follow sodium nitrite with IV sodium thiosulfate. ADULT: Administer 50 mL (12.5 g) of a 25% solution IV; PEDIATRIC: 1 mL/kg of a 25% solution (250 mg/kg), not to exceed 50 mL (12.5 g) total dose (Prod Info NITHIODOTE intravenous injection solution, 2011).
b) A second dose, one-half of the first dose, may be administered if signs of cyanide toxicity reappear (Prod Info NITHIODOTE intravenous injection solution, 2011).
c) Sodium thiosulfate is usually used in combination with sodium nitrite but may be used alone (Prod Info sodium thiosulfate IV injection, 2003).
d) Sodium thiosulfate can be administered without sodium nitrite in patients at risk to develop further methemoglobinemia (ie excessive methemoglobinemia or hypotension after initial sodium nitrite administration or in the presence of methemoglobinemia or carboxyhemoglobin in patients with smoke inhalation due to fire). Sodium thiosulfate can also be used in combination with hydroxocobalamin to treat cyanide poisoning (Howland, 2011)
e) CONTINUOUS INFUSION: It has been suggested that a continuous infusion of sodium thiosulfate be given after the initial bolus to maintain high thiosulfate levels. Low sodium intravenous fluids are required to avoid sodium overload. If large amounts of sodium thiosulfate are required, hemodialysis may be necessary to maintain a physiologic serum sodium level (Turchen et al, 1991a).
f) ADVERSE EVENTS: Sodium thiosulfate does not usually produce significant toxicity. Possible adverse events include hypotension, headache, nausea, vomiting, disorientation, and prolonged bleeding time (Prod Info NITHIODOTE intravenous injection solution, 2011).

G) ACIDOSIS

1) METABOLIC ACIDOSIS: Treat severe metabolic acidosis (pH less than 7.1) with sodium bicarbonate, 1 to 2 mEq/kg is a reasonable starting dose(Kraut & Madias, 2010). Monitor serum electrolytes and arterial or venous blood gases to guide further therapy.
2) Acidosis may be difficult to correct prior to administration of specific antidotes in serious cyanide poisoning cases (Hall & Rumack, 1986).

H) 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).

I) METHEMOGLOBINEMIA

1) While overwhelming methemoglobinemia has been reported following sodium nitrite therapy for cyanide poisoning in a child (Berlin, 1970), such instances are rare and usually occur in situations where the patient has been given excessive nitrite doses.

a) Inducing a "therapeutic methemoglobin level" of 20% to 30% may not be necessary to insure satisfactory clinical outcome because clinical response has occurred with methemoglobin levels in the range of 3.6% to 9.2% (DiNapoli et al, 1989) (Johnson et al, 1989).

2) If excessive methemoglobinemia occurs, some authors recommend that methylene or toluidine blue should not be used, as they could cause the release of cyanide from the cyanmethemoglobin complex.

a) In this instance, emergency exchange transfusion has been suggested (Berlin, 1970).
b) Hyperbaric oxygen therapy could be used to support the patient while preparations for exchange transfusion are being made.

3) However, methylene or toluidine blue have been used successfully in this setting without worsening the course of the cyanide poisoning (van Heijst et al, 1987).

a) There is some controversy over whether or not the induction of methemoglobinemia is the sodium nitrite mechanism of action in cyanide poisoning.

1) Administration of toluidine blue to prevent methemoglobinemia in cyanide poisoned rats treated with either sodium nitrite/sodium thiosulfate or 4-dimethylaminophenol did not affect the ability of these agents to restore cytochrome oxidase activity (Holmes et al, 1982; Way, 1983; Tadic, 1992).

b) As long as intensive care monitoring and further antidote doses are readily available, methylene or toluidine blue can most likely be safely administered in this setting.

J) DICOBALT EDETATE

1) Kelocyanor(R) (dicobalt-EDTA) is a highly effective cyanide chelating agent currently used clinically in Europe, Israel, and Australia (Davison, 1969; Hillman et al, 1974). It is not available in the USA.
2) PRECAUTIONS

a) Serious adverse effects include hypotension, cardiac dysrhythmias, decreased cerebral blood flow, and angioedema (Dodds & McKnight, 1985; Wright & Vesey, 1986). These adverse reactions are magnified when a patient does not have cyanide intoxication (Pronczuk de Garbino & Bismuth, 1981; Tyrer, 1981). Therefore, KELOCYANOR(R) SHOULD NOT BE USED IN CASES of MILD CYANIDE POISONING or DIAGNOSTIC UNCERTAINTY (Peden et al, 1986; Tyrer, 1981).
b) Severe anaphylactoid reactions with periorbital and massive facial edema and airway compromise may also occur (Dodds & McKnight, 1985; Wright & Vesey, 1986).
c) ADVERSE EFFECTS may include nausea, vomiting, tachycardia, hypotension, hypertension, anaphylactic reactions, massive facial and neck edema, chest pain, diaphoresis, nervousness, tremulousness, gastrointestinal hemorrhages, seizures, cardiac irregularities, and rashes (Prod Info, 1986; Prod Info, 1987; (Davison, 1969; Tyrer, 1981; Hillman et al, 1974).

K) 4-DIMETHYLAMINOPHENOL HYDROCHLORIDE

1) 4-DMAP is a methemoglobin-inducing agent used in some European countries for the treatment of acute cyanide poisoning. A more rapid onset of methemoglobin production is observed following administration of 4-DMAP than following sodium nitrite. Methemoglobin peaks at 5 minutes after DMAP versus 30 minutes after sodium nitrite (Kruszyna et al, 1982; Moore et al, 1987; Weger, 1990).
2) The dose of 4-DMAP is 3 mg/kg and it is coadministered with sodium thiosulfate at doses described above.
3) Excessive methemoglobinemia may be a major complication following the use of this agent (van Dijk et al, 1986). Hemolysis may occur with therapeutic doses (van Heijst et al, 1987).

L) EXPERIMENTAL THERAPY

1) STROMA-FREE METHEMOGLOBIN SOLUTION

a) Stroma-free methemoglobin (erythrocytes having hemoglobin oxidized to the ferric form followed by cell membrane removal in vitro) attenuates lethality and prevents hemodynamic changes in cyanide poisoning experimental animal models (Breen et al, 1996) (Ten Eyck et al, 1985). This allow provision of exogenous methemoglobin without compromising the oxygen-carrying capacity of native hemoglobin and removal of cell membranes eliminates antigenicity (Marrs, 1988a).
b) It has not been studied in human poisoning cases and is not available for human administration.

2) DISULFIRAM

a) CASE REPORT: A 30-year-old man presented with a cholinergic toxic syndrome following a witnessed ingestion of aldicarb. Laboratory data was unremarkable except for an elevated osmolal gap (31 mOsm/kg). Toxicologic analysis of blood and urine was negative for antidepressants, salicylates, paracetamol, benzodiazepines, barbiturates, phenothiazines, opioids, paraquat, and paranitrophenol. Gas chromatography with flame ionization identified the presence of acetone, suggested to be the cause of the elevated osmolal gap. Following supportive care, the cholinergic toxic syndrome resolved; however, 12 hours later, the patient developed agitation and severe lactic acidosis. Suspecting cyanogenic toxicity, IV hydroxocobalamin (5 g) and IV sodium thiosulfate (12.5 g) were administered, resulting in a decrease in the plasma lactate level and clinical improvement. Following repeat inspection of the gas chromatogram, it was suspected that acetonitrile was present instead of acetone, and was confirmed following injection of an acetonitrile standard into the gas chromatogram that produced a peak that completely corresponded with the peak in the patient sample. Laboratory analysis revealed elevated blood cyanide and plasma thiocyanate levels. Despite treatment, lactic acidosis recurred, requiring 2 more doses of hydroxocobalamin and sodium thiosulfate. However, the patient's elevated thiocyanate levels persisted and his lactate levels increased, and treatment with disulfiram 400 mg orally was initiated, resulting in resolution of his metabolic acidosis, the slowed decrease in acetonitrile concentration, and complete recovery. Interview of the patient revealed that he had ingested acetonitrile with aldicarb in a suicide attempt (De Paepe et al, 2016).

1) It is suggested that disulfiram inhibited acetonitrile metabolism by inhibition of CYP2E1 enzymes, as evidenced by the slowing in the decrease in acetonitrile concentration (De Paepe et al, 2016).

M) HYPOTENSIVE EPISODE

1) SUMMARY

a) Infuse 10 to 20 milliliters/kilogram of isotonic fluid and keep the patient supine. If hypotension persists, administer dopamine or norepinephrine. Consider central venous pressure monitoring to guide further fluid therapy.

2) DOPAMINE

a) DOSE: Begin at 5 micrograms per kilogram per minute progressing in 5 micrograms per kilogram per minute increments as needed (Prod Info dopamine hcl, 5% dextrose IV injection, 2004). If hypotension persists, dopamine may need to be discontinued and a more potent vasoconstrictor (eg, norepinephrine) should be considered (Prod Info dopamine hcl, 5% dextrose IV injection, 2004).
b) CAUTION: If ventricular dysrhythmias occur, decrease rate of administration (Prod Info dopamine hcl, 5% dextrose IV injection, 2004). Extravasation may cause local tissue necrosis, administration through a central venous catheter is preferred (Prod Info dopamine hcl, 5% dextrose IV injection, 2004).

3) NOREPINEPHRINE

a) PREPARATION: 4 milligrams (1 amp) added to 1000 milliliters of diluent provides a concentration of 4 micrograms/milliliter of norepinephrine base. Norepinephrine bitartrate should be mixed in dextrose solutions (dextrose 5% in water, dextrose 5% in saline) since dextrose-containing solutions protect against excessive oxidation and subsequent potency loss. Administration in saline alone is not recommended (Prod Info norepinephrine bitartrate injection, 2005).
b) DOSE

1) ADULT: Dose range: 0.1 to 0.5 microgram/kilogram/minute (eg, 70 kg adult 7 to 35 mcg/min); titrate to maintain adequate blood pressure (Peberdy et al, 2010).
2) CHILD: Dose range: 0.1 to 2 micrograms/kilogram/minute; titrate to maintain adequate blood pressure (Kleinman et al, 2010).
3) CAUTION: Extravasation may cause local tissue ischemia, administration by central venous catheter is advised (Peberdy et al, 2010).

N) ACUTE LUNG INJURY

1) ONSET: Onset of acute lung injury after toxic exposure may be delayed up to 24 to 72 hours after exposure in some cases.
2) NON-PHARMACOLOGIC TREATMENT: The treatment of acute lung injury is primarily supportive (Cataletto, 2012). Maintain adequate ventilation and oxygenation with frequent monitoring of arterial blood gases and/or pulse oximetry. If a high FIO2 is required to maintain adequate oxygenation, mechanical ventilation and positive-end-expiratory pressure (PEEP) may be required; ventilation with small tidal volumes (6 mL/kg) is preferred if ARDS develops (Haas, 2011; Stolbach & Hoffman, 2011).

a) To minimize barotrauma and other complications, use the lowest amount of PEEP possible while maintaining adequate oxygenation. Use of smaller tidal volumes (6 mL/kg) and lower plateau pressures (30 cm water or less) has been associated with decreased mortality and more rapid weaning from mechanical ventilation in patients with ARDS (Brower et al, 2000). More treatment information may be obtained from ARDS Clinical Network website, NIH NHLBI ARDS Clinical Network Mechanical Ventilation Protocol Summary, http://www.ardsnet.org/node/77791 (NHLBI ARDS Network, 2008)

3) FLUIDS: Crystalloid solutions must be administered judiciously. Pulmonary artery monitoring may help. In general the pulmonary artery wedge pressure should be kept relatively low while still maintaining adequate cardiac output, blood pressure and urine output (Stolbach & Hoffman, 2011).
4) ANTIBIOTICS: Indicated only when there is evidence of infection (Artigas et al, 1998).
5) EXPERIMENTAL THERAPY: Partial liquid ventilation has shown promise in preliminary studies (Kollef & Schuster, 1995).
6) CALFACTANT: In a multicenter, randomized, blinded trial, endotracheal instillation of 2 doses of 80 mL/m(2) calfactant (35 mg/mL of phospholipid suspension in saline) in infants, children, and adolescents with acute lung injury resulted in acute improvement in oxygenation and lower mortality; however, no significant decrease in the course of respiratory failure measured by duration of ventilator therapy, intensive care unit, or hospital stay was noted. Adverse effects (transient hypoxia and hypotension) were more frequent in calfactant patients, but these effects were mild and did not require withdrawal from the study (Wilson et al, 2005).
7) However, in a multicenter, randomized, controlled, and masked trial, endotracheal instillation of up to 3 doses of calfactant (30 mg) in adults only with acute lung injury/ARDS due to direct lung injury was not associated with improved oxygenation and longer term benefits compared to the placebo group. It was also associated with significant increases in hypoxia and hypotension (Willson et al, 2015).

Inhalation Exposure

6.7.1)

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)

A) OXYGEN

1) Administer 100% humidified supplemental oxygen with assisted ventilation as required.

B) Treatment should include recommendations listed in the ORAL EXPOSURE section when appropriate.

Eye Exposure

6.8.1)

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)

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)

A) SKIN ABSORPTION

1) Dermal exposure could result in absorption and systemic cyanide poisoning (Pozzani et al, 1959).

B) Treatment should include recommendations listed in the ORAL EXPOSURE section when appropriate.

Enhanced Elimination

1) Hemodialysis may be an effective adjunct treatment in situations that include severe acid-base derangements, renal insufficiency or failure by increasing thiocyanate clearance, thereby favoring thiosulfate-cyanide reaction to thiocyanate (Wesson et al, 1985).

a) It has, however, been used in only one reported case each of cyanide poisoning or acetonitrile poisoning, and antidote therapy with sodium nitrite and sodium thiosulfate was also administered (Wesson et al, 1985; Turchen et al, 1991a).

2) Hemodialysis and charcoal hemoperfusion were performed in an adult who ingested 59 mL of acetonitrile, from 66 to 70 hours postingestion. This resulted in correction of hypernatremia secondary to thiosulfate administration and reduction of thiocyanate levels to subtoxic levels. Removal of acetonitrile or cyanide could not be documented by these procedures. If large amounts of sodium thiosulfate are required, hemodialysis may be necessary to maintain a physiologic serum sodium level (Turchen et al, 1991a).
3) Limited animal studies, using historical controls and only a few animals, have so far shown some potential effectiveness of hemodialysis when combined with thiosulfate infusion in cyanide poisoning (Gonzales & Sabatini, 1989).
4) Hemodialysis cannot be considered standard therapy for cyanide poisoning at this time.

1) Charcoal hemoperfusion has also been used in one reported case of cyanide poisoning (Kreig & Saxena, 1987).

a) This patient also received supportive measures and sodium nitrite/thiosulfate antidotes.
b) The outcome in this case was no different from that of other patients treated similarly without hemoperfusion.

2) Hemoperfusion cannot be considered standard therapy for cyanide poisoning at this time.

Abstracts

Case Reports

1) ROUTE OF EXPOSURE

a) INHALATION: Fifteen painters were exposed to vapors from a liquid containing 30% to 40% acetonitrile (Amdur, 1959). These painters inhaled the vapors for several hours per day for 2 days, but concentration was unknown. Those with minor symptoms developed nausea, vomiting, headache, and lassitude. More seriously poisoned patients experienced a range of symptoms including extreme weakness, respiratory depression, coma, shock, hematemesis, and seizures. Workers had onset of symptoms varying from 4 to 12 or more hours after exposure.

1) One painter's symptoms began approximately 4 hours after leaving the job on the second exposure day. Signs and symptoms included nausea, vomiting, spitting blood, seizures, and coma, and the patient died approximately 14 hours after the last exposure. At autopsy, cyanide concentrations were 796 mcg% in whole blood, 215 mcg% in urine, 204 mcg% in kidney, 318 mcg% in spleen, and 128 mcg% in lungs.
2) Another painter developed signs and symptoms including nausea, vomiting, hypotension, shallow respirations, decreased respiratory rate, and diminished deep tendon reflexes. Improvement occurred in a few hours following treatment with oxygen, blood transfusion, ascorbic acid, and sodium thiosulfate.
3) A third painter developed nausea, diarrhea, and listlessness. On admission there were slate gray cyanosis and semiconscious with a low pulse rate and body temperature. Respirations were slow and shallow, motor power was impaired, and deep tendon reflexes were absent. Noticeable improvement occurred one-half hour following treatment with oxygen, blood transfusion, ascorbic acid, and sodium thiosulfate.
4) Several other workers who were less seriously affected had symptoms that included headache, nausea, and weakness.

b) INHALATION: Dequidt et al (1974) reported a fatal inhalation exposure in a 19-year-old worker in an industrial photographic laboratory who used acetonitrile mixed with boiling water.

1) The patient experienced nausea and abdominal pains about 4 hours after leaving work, vomiting occurred during the night, and the next morning the patient was comatose and seizing. Hypotension and cardiac arrest (with successful resuscitation) developed.
2) The nature of the poisoning was not apparent until the second hospital day. Blood cyanide level was 3.76 mcg/mL. The patient was treated with cobalt tetracemate and dihydroxycobalamin (2 ampules of dicobalt EDTA without apparent response).
3) Blood acetonitrile level and blood cyanide level on the third hospital day were 1.2 mg/dL and 10.38 mcg/mL, respectively. Four grams of hydroxycobalamin were given without apparent response. The patient died of cardiovascular collapse on the fifth hospital day (Dequidt et al, 1974a).

c) ORAL: A 22-year-old woman presented approximately 8 hours after presumed ingestion of an unknown amount of a substance later identified to contain acetone and acetonitrile. The patient remained drowsy but arousable over the next 18 hours and then became agitated followed by grand mal seizures and cardiac arrest. Following successful resuscitation, hypotension and acidosis developed that were refractory to sodium bicarbonate and vasopressors. Death occurred approximately 30 hours after ingestion.

1) Although neither acetonitrile nor cyanide were measured in blood or urine and there was no report of witnessing the patient's ingestion, the seizures, hypotension, and metabolic acidosis several hours after ingestion were consistent with previously reported cases of acetonitrile poisoning (Boggild et al, 1990).

d) ORAL: A middle aged couple died after an evening of drinking at home. Their son had returned home in the early morning and found the father vomiting; he was told that the mother was also ill. The couple were mixing drinks from reagent bottles labeled as ethanol that the man had brought home from work. The solution in the bottles was found to contain acetonitrile (Jones et al, 1992).
e) ORAL: A 26-year-old man reportedly drank 40 mL of acetonitrile. Nausea and vomiting occurred 3 hours after ingestion. The patient's condition was later characterized by coma, respiratory insufficiency, metabolic acidosis, shock, and 2 episodes of cardiac arrest.

1) Ten hours after ingestion, the patient was treated with cyanide antidotes but remained in a coma for 6 days. Muscle and liver degeneration occurred, but the patient eventually recovered. Thiocyanate was detectable in urine for 20 days after the poisoning (Jaeger et al, 1977).

f) ORAL: A 39-year-old woman ingested 59 mL of artificial nail remover containing 99% acetonitrile in a suicide attempt. The patient was asymptomatic for 7 hours, and then vomited. Gastric lavage was performed and activated charcoal given. The patient became unresponsive and experienced a seizure 11.5 hours after ingestion.

1) The patient's blood pH had decreased from 7.48 to 6.84. Rapid clinical improvement followed administration of the Cyanide Antidote Kit.
2) At approximately three 8 hour intervals after antidote therapy, the vital signs deteriorated. Acidosis and increasing whole blood cyanide levels were observed. At each occurrence the patient received additional antidotal therapy.
3) At 3 days post-ingestion, hemodialysis and charcoal hemoperfusion were performed to attempt to reduce a blood cyanide level of 11.76 mcg/mL. The patient recovered fully (Turchen et al, 1991a).

g) A 39-year-old woman ingested 25 grams of acetonitrile, vomited for one-half, and presented to the hospital 2 hours after ingestion with dizziness. Eleven hours after ingestion, the patient was nauseated, confused, diaphoretic, and tachycardic. Kussmaul respirations, metabolic acidosis, and rapid onset of coma developed.

1) The patient was given sodium nitrite and sodium thiosulfate intravenously. Methemoglobin level was 15% 2 hours later. Grand mal seizures occurred and 32 hours post-ingestion the patient was hypotensive and tachycardic with persistent acidosis.
2) The patient was given additional doses of sodium nitrite and sodium thiosulfate, including a continuous infusion of 3% sodium nitrite. The patient was discharged 26 days after admission. Peak blood acetonitrile and cyanide levels were 64 mcg/dL (7.5 hours post-ingestion) and 1.7 mcg/mL (17 hours post-ingestion), respectively (Mueller & Borland, 1997).

h) ORAL: A 30-year-old man drank approximately 5 mL of acetonitrile in a suicide attempt. Sodium thiosulfate 1 gram was given at 4.5 hours post-ingestion en route to the hospital. The patient presented with malaise; an additional 31 grams of sodium thiosulfate was given. The patient never developed complications. Measured acetonitrile level was 8 mg/dL and peak whole blood cyanide level was 17.3 mcg/mL (Michaelis et al, 1991).

1) ROUTE OF EXPOSURE

a) DERMAL: A 2-year-old, 12-kg boy was found with an open bottle of sculptured nail remover, with approximately 30 mL that had spilled on him and his bed. Eight hours post-exposure, the patient was found poorly responsive and had vomited. On admission to the hospital, hypotension and metabolic acidosis were present. The patient responded well to supportive care with oxygen, fluid resuscitation, and 20 mmol sodium bicarbonate. Cyanide antidotes were not administered. The patient recovered.

1) Initial cyanide level at approximately 12 hours after exposure was 6 mcg/mL (231 mcmol/L). At 61 hours after ingestion whole-blood cyanide level was 0.39 mcg/mL (15 mcmol/L) (Caravati & Litovitz, 1988).

b) ORAL: A 16-month-old, 11.8-kg boy ingested 15 to 30 mL of Super Nail Nail Off containing 98% to 100% acetonitrile. Spontaneous vomiting occurred approximately 20 minutes after ingestion. Later, the child was put to bed. The mother noted he was breathing noisily and heavily in his sleep. The next morning, about 12 hours after ingestion, the child was found dead in his crib (Caravati & Litovitz, 1988).
c) ORAL: A 2-year-old 15.8 kg girl ingested 5 to 10 mL of Nailene Glue Remover containing 84% acetonitrile. Initially the patient was asymptomatic and was evaluated and discharged from the emergency department. Twelve hours later the child was restless, moaning, and vomiting.

1) 14 hours after ingestion 3 tonic-clonic seizures were observed. Upon presentation to the emergency department, coma was present and whole blood cyanide level was 70.1 mcmol/L (189 mcg/dL). Treatment included administration of oxygen and a cyanide antidote kit. The patient awakened within minutes after treatment and fully recovered over 2 days (Kurt et al, 1991).

d) ORAL: A 3-year-old, 17.2 kg child ingested 15 to 30 mL of a glue-on nail remover containing 95% or more of acetonitrile, but was asymptomatic on presentation about 30 minutes postingestion. Gastric lavage was done and activated charcoal given.

1) Spontaneous emesis occurred 13 hours after ingestion. Mental confusion, repeated emesis, seizures, and crying developed 16 hours postingestion. Arterial blood gas values were PO2 of 316 mmHg, PCO2 of 25 mmHg, bicarbonate of 16.1 mmol/L, and pH of 7.42. Sodium thiosulfate was given at a dose of 35 mL of 25 percent solution over 30 minutes.
2) Clinical symptoms resolved and the child remained asymptomatic until discharge at 42 hours after ingestion (Geller et al, 1991).

e) ORAL: A 23-month-old child ingested approximately 60 mL of a 98% acetonitrile solution. Vomiting began 6 hours post-ingestion. The child was evaluated 6 hours later at a hospital and did not appear ill. At 24 hours post-ingestion the child became nonresponsive and his oxygen saturation was 93% on supplemental oxygen. Blood pH was never low; lactic acid was elevated.

1) Administration of amyl nitrate did not result in clinical improvement. Sodium thiosulfate was administered every 4 hours for 5 doses. The child's mental status returned to normal, oxygen saturation increased to 98% on room air, and discharge was on the third hospital day (Losek et al, 1991).

Range Of Toxicity

Summary

Minimum Lethal Exposure

1) ORAL

a) Ingestion of 1 to 2 g/kg of acetonitrile is lethal. Acute acetonitrile toxicity is due mainly to cyanide formation and the signs and symptoms of toxicity are the same as acute cyanide poisoning (IPCS, 1993).
b) CHILD: A 16-month-old 11.8-kg child ingested 15 to 30 mL (1.2 to 2.4 g/kg) of a nail glue remover containing 98% to 100% acetonitrile, and was found dead the following morning. No treatment was given (Caravati & Litovitz, 1988). The amount contained in an average swallow, 5 to 10 mL, is potentially lethal if untreated (Kurt et al, 1991).

2) INHALATION

a) Fifteen painters were exposed to vapors from a liquid containing 30% to 40% acetonitrile. These painters inhaled the vapors for several hours per day for 2 days, but concentration was unknown. Those with minor symptoms developed nausea, vomiting, headache, and lassitude. More seriously poisoned patients experienced a range of symptoms including extreme weakness, respiratory depression, coma, shock, hematemesis, and seizures .

a) Reported lethal inhalation exposures vary from case to case, even among individuals working on the same job. Symptoms associated with exposure to acetonitrile vapors show delayed onset and may indicate that acetonitrile is metabolized to cyanide more slowly than other, similar nitriles. The final clinical picture is the result of the effects of the intact cyanide molecule combined with the effects of gradually released cyanide ions (Clayton & Clayton, 1994; IPCS, 1993).

Maximum Tolerated Exposure

1) DERMAL

a) CHILD: Dermal exposure of approximately 30 mL of a 98% to 100% acetonitrile-containing nail product, in a 2-year-old boy, resulted in vomiting, hypotension, and metabolic acidosis. With supportive care, the patient recovered (Caravati & Litovitz, 1988a).

2) ORAL

a) Ingestion of acetonitrile typically causes labored breathing, ataxia, cyanosis, and coma (Clayton & Clayton, 1994).

1) CHILD: Oral ingestion of 5 to 10 mL of glue-on nail remover containing 84% acetonitrile by a 2-year-old child resulted in severe toxicity (coma, seizures, acidosis), which responded to the cyanide antidote kit (Kurt et al, 1991).
2) CHILD: Oral ingestion of 15 to 30 mL of a glue-on nail remover containing 95% acetonitrile by a 3-year-old child resulted in vomiting and seizures, which responded to a single sodium thiosulfate infusion. Gastric decontamination was performed about 30 minutes postingestion (Geller et al, 1991).
3) ADULT: A 60 kg adult male ingested approximately 5 mL acetonitrile and survived with treatment (Michaelis et al, 1991).

3) INHALATION

a) Exposure to acetonitrile vapor concentrations of up to 500 ppm causes irritation to the mucous membranes, headache, dizziness, and nausea. At extremely high concentrations, it can cause convulsions, coma, and death (Baselt & Cravey, 1995; Hathaway et al, 1996; Synder et al, 1990).
b) Human inhalation studies revealed that exposure to 40 ppm for 4 hours produced no reported adverse effects in three subjects; the subjects had no detectable blood cyanide levels, but one of the subjects had a slightly elevated urinary thiocyanate level. Two subjects exposed to 80 ppm for 4 hours reported no subjective responses, had no blood cyanide, and an inconsistent urinary thiocyanate level. Two subjects exposed to 160 ppm for 4 hours also did not show any changes in blood cyanide or urinary thiocyanate levels; however, one subject reported a slight flushing of the face 2 hours after exposure and a slight feeling of bronchial tightness 5 hours after exposure. Evidence for brief inhalations of lower concentrations of acetonitrile cannot be determined by blood cyanide or urinary thiocyanate levels (ACGIH, 1991; Clayton & Clayton, 1994; Hathaway et al, 1996; IPCS, 1993).
c) Fifteen painters were exposed to vapors from a liquid containing 30% to 40% acetonitrile. These painters inhaled the vapors for several hours per day for 2 days, but concentration was unknown. Those with minor symptoms developed nausea, vomiting, headache, and lassitude. More seriously poisoned patients experienced a range of symptoms including extreme weakness, respiratory depression, coma, shock, hematemesis, and seizures (Amdur, 1959).

4) Serum thiocyanate levels of less than 120 mg/L are associated with symptoms such as weakness, nausea, and abdominal pain. Severe toxicity due to exposure to high concentrations of acetonitrile was observed in 2 workers who had blood cyanide concentrations of 3 to 11 mg/L and serum thiocyanate levels of 160 to 230 mg/L (Baselt & Cravey, 1995).

Serum Plasma Blood Concentrations

7.5.2)

A) TOXIC CONCENTRATION LEVELS

1) CASE REPORTS -

a) In the fatal case described by Dequidt et al (1974), the acetonitrile blood level on the third day following exposure was 1,176 micrograms per deciliter.

1) A urine acetonitrile level from this patient obtained on the fourth day following exposure was 31.1 milligrams per liter.
2) At postmortem examination, the following acetonitrile levels were found in various tissues: heart, 613 micrograms/100 grams; lungs, 287 micrograms/100 grams; liver, 1,184 micrograms/100 grams; spleen, 934 micrograms/100 grams; kidneys, 1,355 micrograms/100 grams; pancreas and bladder, trace amounts (Dequidt et al, 1974).

b) Swanson & Krasselt (1994) report a fatal poisoning from an unknown source and dose of acetonitrile. A 39-year-old female was found dead approximately 30 hours after being seen alive. Postmortem laboratory analysis revealed acetonitrile concentrations of 31 and 56 milligrams/dL in two blood samples and a urine acetonitrile concentration of 44 milligrams/dL.
c) Measured peak whole blood cyanide levels in fatal cases have been 4.4, 7.96, and 10.38 micrograms per milliliter (Swanson & Krasselt, 1994; Dequidt et al, 1974; Amdur, 1959).

1) In one case, the peak measured level of 10.38 micrograms per milliliter was obtained on the third day following exposure, and had increased from 3.76 micrograms per milliliter on the second postexposure day (Dequidt et al, 1974).

d) Measured whole blood cyanide levels in survivors of acetonitrile exposure have ranged from undetectable to up to 0.72 micrograms per milliliter in very mildly symptomatic patients to 3.06 and 10.38 micrograms per milliliter in seriously ill patients who received treatment with sodium thiosulfate (Amdur, 1959).

1) One of these seriously ill survivors also was noted to have an increase in whole blood cyanide level from 9.7 micrograms per milliliter on the day following exposure to 10.38 micrograms per milliliter on the second postexposure day (Amdur, 1959).
2) A less seriously ill patient had an initial whole blood cyanide level of 0.58 micrograms per milliliter, but still had a level of 0.57 micrograms per milliliter 7 days after exposure (Amdur, 1959).

e) A 2-year-old child exposed to an acetonitrile-containing cosmetic had a reported whole blood cyanide level of 6 micrograms/milliliter (231 micromoles/liter) at 12 hours postexposure and 0.39 micrograms/milliliter (15 micromoles/liter) at 61 hours postexposure (Caravati & Litovitz, 1988).
f) The whole blood cyanide level in a two-year-old child approximately 14 hours after ingestion of nail remover containing 84 percent acetonitrile was 70.1 mcmol/L (189 mcg/dL) (Kurt et al, 1991).
g) Eight hours after ingestion of 60 mL of 99 percent acetonitrile a 39-year-old female's whole blood cyanide level was 313 mcg/dL (Turchen & Manoguerra, 1989).

2) SUMMARY

a) FATAL POISONINGS -

AGE	EXPOSURE ROUTE	BLOOD ACETONITRILE (mg/dL)	WHOLE BLOOD CYANIDE (mcg/mL)
Adult	Inhalation	--	8.0
Adult	Inhalation	1.2	1.1
16 mo	Ingestion	--	3.1
Adult	Ingestion	80	2.4
Adult	Ingestion	77	4.5
Adult	Unknown	56	4.4

1) (REFERENCES - Amdur, 1959; Dequidt, 1974; (Caravati & Litovitz, 1988) Jones, 1992;) (Swanson & Krasselt, 1994) ACUTE POISONING SURVIVORS -

AGE	EXPOSURE ROUTE	BLOOD ACETONITRILE (mg/dL)	WHOLE BLOOD CYANIDE (mcg/mL)
Adult	Inhalation	--	3.1
Adult	Inhalation	--	10
2 years	Ingestion	--	6.0
3 years	Ingestion	--	1.2
Adult	Ingestion	--	13
Adult	Ingestion	8	17.3
2 years	Ingestion	--	3.8
Adult	Ingestion	--	1.7

Workplace Standards

1) Editor's Note: The listed values are recommendations or guidelines developed by ACGIH(R) to assist in the control of health hazards. They should only be used, interpreted and applied by individuals trained in industrial hygiene. Before applying these values, it is imperative to read the introduction to each section in the current TLVs(R) and BEI(R) Book and become familiar with the constraints and limitations to their use. Always consult the Documentation of the TLVs(R) and BEIs(R) before applying these recommendations and guidelines.

a) Adopted Value

1) Acetonitrile

a) TLV:

1) TLV-TWA: 20 ppm
2) TLV-STEL:
3) TLV-Ceiling:

b) Notations and Endnotes:

1) Carcinogenicity Category: A4
2) Codes: Skin
3) Definitions:

a) A4: Not Classifiable as a Human Carcinogen: Agents which cause concern that they could be carcinogenic for humans but which cannot be assessed conclusively because of a lack of data. In vitro or animal studies do not provide indications of carcinogenicity which are sufficient to classify the agent into one of the other categories.
b) Skin: This refers to the potential significant contribution to the overall exposure by the cutaneous route, including mucous membranes and the eyes, either by contact with vapors or, of likely greater significance, by direct skin contact with the substance. It should be noted that although some materials are capable of causing irritation, dermatitis, and sensitization in workers, these properties are not considered relevant when assigning a skin notation. Rather, data from acute dermal studies and repeated dose dermal studies in animals or humans, along with the ability of the chemical to be absorbed, are integrated in the decision-making toward assignment of the skin designation. Use of the skin designation provides an alert that air sampling would not be sufficient by itself in quantifying exposure from the substance and that measures to prevent significant cutaneous absorption may be warranted. Please see "Definitions and Notations" (in TLV booklet) for full definition.

c) TLV Basis - Critical Effect(s): LRT irr
d) Molecular Weight: 41.05

1) For gases and vapors, to convert the TLV from ppm to mg/m(3):

a) [(TLV in ppm)(gram molecular weight of substance)]/24.45

2) For gases and vapors, to convert the TLV from mg/m(3) to ppm:

a) [(TLV in mg/m(3))(24.45)]/gram molecular weight of substance

e) Additional information:

B) NIOSH REL and IDLH Values for CAS75-05-8 (National Institute for Occupational Safety and Health, 2007):

1) Listed as: Acetonitrile
2) REL:

a) TWA: 20 ppm (34 mg/m(3))
b) STEL:
c) Ceiling:
d) Carcinogen Listing: (Not Listed) Not Listed
e) Skin Designation: Not Listed
f) Note(s):

3) IDLH:

a) IDLH: 500 ppm
b) Note(s): Not Listed

C) Carcinogenicity Ratings for CAS75-05-8 :

1) ACGIH (American Conference of Governmental Industrial Hygienists, 2010): A4 ; Listed as: Acetonitrile

2) EPA (U.S. Environmental Protection Agency, 2011): D ; Listed as: Acetonitrile

a) D : Not classifiable as to human carcinogenicity.

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 ; Listed as: Acetonitrile
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 CAS75-05-8 (U.S. Occupational Safety, and Health Administration (OSHA), 2010):

1) Listed as: Acetonitrile
2) Table Z-1 for Acetonitrile:

a) 8-hour TWA:

1) ppm: 40

a) Parts of vapor or gas per million parts of contaminated air by volume at 25 degrees C and 760 torr.

2) mg/m3: 70

a) Milligrams of substances per cubic meter of air. When entry is in this column only, the value is exact; when listed with a ppm entry, it is approximate.

3) Ceiling Value:
4) Skin Designation: No
5) Notation(s): Not Listed

Toxicity Information

7.7.1)

A) References: Lewis, 1996 RTECS, 1999

1) LD50- (INTRAPERITONEAL)MOUSE:

a) 175 mg/kg

2) LD50- (ORAL)MOUSE:

a) 269 mg/kg

3) LD50- (SUBCUTANEOUS)MOUSE:

a) 4480 mg/kg

4) LD50- (INTRAPERITONEAL)RAT:

a) 850 mg/kg

5) LD50- (ORAL)RAT:

a) 2730 mg/kg
b) 2460 mg/kg

6) LD50- (SUBCUTANEOUS)RAT:

a) 3500 mg/kg

7) TCLo- (INHALATION)HUMAN:

a) 160 ppm for 4H

8) TCLo- (INHALATION)MOUSE:

a) 800 ppm for 6H/13W-I

9) TCLo- (INHALATION)RAT:

a) Female, 1800 ppm for 6H -- at 6-20D of pregnancy, affected post-implantation mortality
b) 655 ppm for 7H/90D-I -- caused chronic pulmonary edema, changes in liver, and changes in renal tubules
c) 800 ppm for 6H/13W-I

Pharmacology Toxicology

Toxicologic Mechanism

1) The interaction of cyanide and cytochrome oxidase is best studied. Cytochrome oxidase is an iron-containing enzyme essential for oxidative phosphorylation and aerobic energy production. Cyanide induces cellular hypoxia by inhibiting the aa3 component of cytochrome oxidase, blocking efficient ATP production.
2) Lactate production is increased as the result of anaerobic energy production in an attempt to maintain ATP production. Pyruvate can no longer enter the Kreb's cycle from the glycolytic pathway and is converted to lactate. Cyanide also causes direct neurotoxicity by lipid peroxidation.

Physicochemical

Physical Characteristics

Ph

1) No information found at the time of this review.

Molecular Weight

Other

1) 40 ppm (Sittig, 1991)
2) The odor sensation is rapidly fatigued; odor is an unreliable index of exposure (Clayton & Clayton, 1994).

Animal Toxicology

References

General Bibliography

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FeedBack

ACETONITRILE

Classification | Detailed evidence-based information

Therapeutic Toxic Class

Specific Substances

Available Forms Sources

Life Support

Clinical Effects

Laboratory Monitoring

Treatment Overview

Range Of Toxicity

Summary Of Exposure

Heent

Cardiovascular

Respiratory

Neurologic

Gastrointestinal

Acid-Base

Dermatologic

Reproductive

Carcinogenicity

Genotoxicity

Monitoring Parameters Levels

Methods

Life Support

Patient Disposition

Monitoring

Oral Exposure

Inhalation Exposure

Eye Exposure

Dermal Exposure

Enhanced Elimination

Case Reports

Summary

Minimum Lethal Exposure

Maximum Tolerated Exposure

Serum Plasma Blood Concentrations

Workplace Standards

Toxicity Information

Toxicologic Mechanism

Physical Characteristics

Ph

Molecular Weight

Other

General Bibliography