EPA 749-F-94-004a     http://www.epa.gov/chemfact/s_acenit.txt

                           prepared by
                           August 1994

 This summary is based on information retrieved from a systematic
search limited to secondary sources (see Appendix A).  These sources
include online databases, unpublished EPA information, government
publications, review documents, and standard reference materials.  No
attempt has been made to verify information in these databases and
secondary sources.

Acetonitrile is metabolized in the body to hydrogen cyanide and    thiocyanate; these chemicals are thought to be
responsible for the  adverse effects of acetonitrile.


 A. Production

    There are four producers of acetonitrile in the United States:
    BP Chemicals; Dupont; J.T. Baker Chemical; and Sterling Chemicals.
    In 1992, 14.7 million kilograms (32.3 million pounds) were
    produced in the United States. (U.S. International Trade
    Commission 1994).

 B. Use

    Acetonitrile has a number of uses, primarily as an extraction
    solvent for butadiene; as a chemical intermediate in pesticide
    manufacturing; and as a solvent for both inorganic and organic
    compounds.  Uses also include use as a starting material for the
    production of acetophenone, alpha-naphthalenacetic acid, thiamine,
    and acetamidine; to remove tars, phenols, and coloring matter
    from petroleum hydrocarbons not soluble in acetonitrile; in the
    production of acrylic fibers; and in pharmaceuticals, perfumes,
    nitrile rubber, and ABS (acrylonitrile-butadiene-styrene) resins
    (HSDB 1994).

 C. Trends

    Because it is a byproduct of acrylonitrile production, production
    trends for acetonitrile should follow trends in acrylonitrile
    production, which are expected to generally mirror trends in
    United States economic growth (Mannsville, "Acrylonitrile," 1992.)


 A. Environmental Release

    Of the total acetonitrile released to the environment in 1992,
    11.3 million pounds were into the atmosphere, 20 million pounds
    were into underground sites, 50 thousand pounds were into surface
    water, and only 29 pounds were onto the land (TRI92 1994).  
    Acetonitrile has been detected in air near ground levels, ranging
    from 2 to 7 ppb in both urban and rural areas (HSDB 1994).  The
    chemical occurs naturally in coal tar and cigarette smoke (HSDB

 B. Transport

    Acetonitrile is expected to adsorb weakly to soils as predicted
    by its KOC value; removal occurs primarily by volatilization and
    leaching into groundwater (HSDB 1994).  Volatilization from
    surface waters is slow due to the high water solubility, moderate
    vapor pressure (91.1 mm Hg), and low Henry's law constant (3.46 x
    10-5 atmùm3/mole) of the chemical (HSDB 1994).  The water
    solubility of acetonitrile suggests that dissolution into clouds
    and raindrops may occur leading to possible removal in rainfall
    (U.S. EPA 1985).


Acetonitrile is metabolized in the body to hydrogen cyanide and
thiocyanate; these chemicals are thought to be responsible for the
adverse effects of acetonitrile.

A. Pharmacokinetics

   1. Absorption - Absorption of acetonitrile occurs after oral,
      dermal, or inhalation exposure.  Although no quantitative
      absorption data were found for oral exposure, signs of acute
      toxicity, observed after oral exposure, indicate that absorption
      occurs (U.S. EPA 1987).  In humans, 74% of acetonitrile was
      absorbed from cigarette smoke held in the mouth for 2 seconds;
      when inhaled into the lungs, absorption increased to 91% (U.S.
      EPA 1985; 1987).  Dogs exposed by inhalation to 16,000 ppm for
      4 hours appeared to reach steady-state blood concentrations
      within 3-4 hours (U.S. EPA 1985; 1987).

  2. Distribution - Acetonitrile and its metabolites are transported
     throughout the body in the blood (U.S. EPA 1985).  After oral or
     inhalation exposures to experimental animals, parent compound or
     metabolites were found in the brain, heart, liver, kidney,
     spleen, blood, stomach, and muscle (U.S. EPA 1985).  After a fatal
     human inhalation exposure, metabolites were also found in those
     organs as well as skin, lungs, intestine, testes, and urine (U.S.
     EPA 1985).

  3. Metabolism - Acetonitrile is metabolized to hydrogen cyanide
     and thiocyanate which are responsible for the toxic effects
     of the chemical (HSDB 1994; U.S. EPA 1985).  Metabolism is
     mediated by the cytochrome P-450 system (U.S. EPA 1985).

  4. Excretion - Acetonitrile is excreted as the parent chemical in
     expired air and as parent or metabolite in urine (U.S. EPA 1985).
     Urinary excretion of thiocyanate following oral exposure in rats
     ranged from 11.8% (U.S. EPA 1985) to 37% (HSDB 1994) of
     administered dose.  Concentrations of acetonitrile of 2.2-20
     microgram/100 mL of urine have been found for heavy smokers
     (U.S. EPA 1985).

B. Acute Toxicity

   Acetonitrile liquid or vapor is irritating to the skin, eyes, and
   respiratory tract.  At high enough doses, death can occur quickly
   from respiratory failure.  Lower doses cause typical symptoms of
   cyanide poisoning such as salivation, nausea, vomiting, anxiety,
   confusion, hyperpnea, dyspnea, rapid pulse, unconsciousness, and

   1. Humans - Liquid or vapor acetonitrile is irritating to eyes,
      skin, nose, and throat (Keith and Walters 1985). Concentrations
      of acetonitrile vapor up to 500 ppm cause irritation of mucous
      membranes (HSDB 1994).  Volunteers were exposed to 40, 80, or
      160 ppm for 4 hours; several hours after exposure one person had
      tightness of the chest after exposure to 40 ppm and another
      experienced flushing of the face and bronchial tightness after
      exposure to 160 ppm (ACGIH 1991).  The concentration of 160 ppm
      is roughly equivalent to a total of 19.5 mg/kg over the 4 hour
      period (see end note 1).  One photographic laboratory worker
      died after "massive" exposure to acetonitrile vapor; gastric
      distress and nausea began about 4 hours after exposure followed
      by hypersalivation, conjunctivitis, low urine output, low blood
      pressure, albumin in urine and cerebrospinal fluid, coma, and
      death due to cardiac and respiratory failure (HSDB 1994).  
      Similar signs and symptoms, including death, occurred in a worker

      painting the interior of a tank with a resin containing 30-40%
      acetonitrile (HSDB 1994).

   2. Animals - Oral LD50 values for acetonitrile in the rat range
      from 2.46 to 6.5 g/kg (U.S. EPA 1985).  The 4-hour inhalation
      LC50 varies with species from 2828 ppm in the rabbit to 16,000
      ppm in the rat; dermal LD50 values of 3.9 and 1.25 g/kg have been
      reported for the rabbit (U.S. EPA 1985).  Deaths occurred in dogs
      exposed by inhalation to 16,000 or 32,000 ppm; necropsy indicated
      pulmonary hemorrhage and vascular congestion (ACGIH 1991).

C. Subchronic/Chronic Toxicity

  Limited information was found on the adverse effects of long term
  human exposure to acetonitrile.  Animals exposed chronically by
  inhalation have liver vacuolization, cerebral hemorrhage, lung
  lesions including focal emphysema and proliferation of alveolar
  septa, and decreases in hematological parameters.  EPA has derived an
  oral reference dose (RfD) (see end note 2) of 0.006 mg/kg/day for
  acetonitrile, based on adverse blood effects observed in animal
  inhalation studies.  Confidence in this RfD is low; it may be changed
  in the near future, pending results of further review now being
  conducted by EPA.

  1. Humans - No information was found on the adverse effects of
     long term human exposure to acetonitrile.  Brief references
     appear in HSDB (1994), suggesting that chronic exposure to
     acetonitrile may cause headache, anorexia, dizziness, weakness,
     and macular, papular, or vesicular dermatitis.  No additional
     information was provided in support of these statements.

  2. Animals - Female mice exposed to 100, 200, or 400 ppm, 6
     hours/day, 5 days/week for 90 days had thymic atrophy at the
     middle and high doses and hepatic vacuolization at the high dose;
     dose-related decreases were observed in hematocrit, blood
     hemoglobin concentration, and erythrocyte and leucocyte counts
     (U.S. EPA 1994).  A no-observed-adverse effect level (NOAEL) for
     this study was 100 ppm (equivalent to 19.3 mg/kg/day).  Based on
     these inhalation data the U.S. EPA (1994) calculated an oral
     reference dose for acetonitrile of 0.006 mg/kg/day.  Similar
     hepatic and blood profile changes were observed in mice exposed to
     200 or 400 ppm 6.5 hours/day, 5 days/week for 13 weeks (ACGIH

     Rats exposed by inhalation to 166, 330, or 655 ppm acetonitrile
     7 hours/day, 5 days/week for 90 days had a dose-responsive
     increase in the severity of lung lesions.  Animals in the low and
     middle dose groups had "histiocytic clumps in alveoli,
     atelectasis, bronchitis or pneumonia"; high dose animals had
     alveolar congestion and focal edema, bronchial inflammation,
     desquamation, and excess mucus as well as swelling of the liver
     and kidneys and cerebral hemorrhage (U.S. EPA 1985; 1987).  Dogs
     and monkeys exposed to 350 ppm, 7 hours/day, 5 days/week for 91
     days had pulmonary lesions including focal emphysema, atelectasis
     and proliferation of alveolar septa; transient depression in
     hematocrit and hemoglobin values also occurred in dogs, and brain
     hemorrhages were observed in monkeys (U.S. EPA 1985; 1987).  
     Male and female mice (groups of 10/sex) were exposed to 25, 50,
     100, 200, or 400 ppm, 6 hours/day for 65 days. Decreased BUN, red
     blood cell counts, and hematocrit occurred in females exposed to
     the two highest doses, and increased liver weights were observed
     in males at 400 ppm and females at 100 and 200 ppm (U.S. EPA

G. Neurotoxicity

  Exposure to high concentrations of acetonitrile causes death by
  respiratory failure and has been shown to cause brain lesions in
  1. Humans - The nervous system is a major target for acetonitrile
     acute toxicity.  Acute exposure may cause salivation, nausea,
     vomiting, anxiety, confusion, hyperpnea, dyspnea, rapid pulse,
     unconsciousness, and convulsions followed by death from
     respiratory failure.  Chronic exposure may cause headache,
     anorexia, dizziness, and weakness (HSDB 1994).

  2. Animals - Acetonitrile inhalation caused cerebral hemorrhages in
     rats exposed to 655 ppm 7 hours/day, 5 days/week, for 90 days and
     monkeys exposed to 350 ppm 7 hours/day, 5 days/week, for 91 days
     (U.S. EPA 1987).