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    This report contains the collective views of an international group of
    experts and does not necessarily represent the decisions or the stated
    policy of the United Nations Environment Programme, the International
    Labour Organisation, or the World Health Organization.

    Published under the joint sponsorship of
    the United Nations Environment Programme,
    the International Labour Organisation,
    and the World Health Organization

    World Health Orgnization
    Geneva, 1983

         The International Programme on Chemical Safety (IPCS) is a
    joint venture of the United Nations Environment Programme, the
    International Labour Organisation, and the World Health
    Organization. The main objective of the IPCS is to carry out and
    disseminate evaluations of the effects of chemicals on human health
    and the quality of the environment. Supporting activities include
    the development of epidemiological, experimental laboratory, and
    risk-assessment methods that could produce internationally
    comparable results, and the development of manpower in the field of
    toxicology. Other activities carried out by the IPCS include the
    development of know-how for coping with chemical accidents,
    coordination of laboratory testing and epidemiological studies, and
    promotion of research on the mechanisms of the biological action of

        ISBN 92 4 154088 5 

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    (c) World Health Organization 1983

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    1.1. Summary
         1.1.1. Properties and analytical methods
         1.1.2. Sources of exposure
         1.1.3. Industrial and environmental levels of exposure
         1.1.4. Monitoring of acrylonitrile uptake
         1.1.5. Absorption, distribution, biotransformation,
                and elimination
         1.1.6. Effects on experimental animals
         1.1.7. Effects on man
    1.2. Recommendations for further research


    2.1. Physical and chemical properties of acrylonitrile
         2.1.1. Physical properties
         2.1.2. Chemical properties
    2.2. Analytical methods
         2.2.1. Sampling methods
         2.2.2. Analytical methods for determining acrylonitrile
        Determination of acrylonitrile and its
                         metabolites in biological materials


    3.1. Natural occurrence
    3.2. Industrial technology, production data, and projection
    3.3. Use patterns
    3.4. Disposal of wastes
    3.5. Accidental release
    3.6. Environmental persistence


    4.1. Exposure of the general population
         4.1.1. Air
         4.1.2. Water
         4.1.3. Food
         4.1.4. Other sources of exposure
    4.2. Occupational exposure
    4.3. Estimate of human exposure from all environmental media


    5.1. Absorption
         5.1.1. Human studies
        Uptake through inhalation
        Dermal absorption
        Uptake by other routes

         5.1.2. Experimental animal studies
        Uptake through inhalation
        Dermal absorption
        Uptake by other routes
    5.2. Distribution and toxicokinetics
         5.2.1. Human studies
         5.2.2. Experimental animal studies
    5.3. Biotransformation and elimination
         5.3.1. Human studies
         5.3.2. Experimental animal studies
        The oxidative pathways of acrylonitrile 
        Mercapturic acids formed in
                         acrylonitrile biotransformation
        The glucuronic acid conjugate
                         of acrylonitrile metabolism
        Quantitative aspects of acrylonitrile
                         biotransformation and elimination of
                         its metabolites



    7.1. Acute toxicity
         7.1.1. Lethal doses and concentrations
        Lethal doses
        Lethal concentrations in air
        Lethal concentrations in water
         7.1.2. Clinical observations
         7.1.3. Biochemical changes and mechanisms of
                acrylonitrile toxicity
        Effect on cytochrome oxidase
        Effect on sulfhydryls
        Interaction with the microsomal oxidation system
                         as a possible mechanism of toxicity
        Observations on the possible participation of 
                         membrane lipid peroxidation in the mechanism 
                         of toxicity
        Studies on antidotes
    7.2. Subacute toxicity
         7.2.1. Inhalation exposure
         7.2.2. Oral administration
         7.2.3. Subcutaneous administration and
                intraperitoneal administration
         7.2.4. Clinical observations in animal studies
        Body weight, food and water consumption
        Organ weights and pathology
        Immune system
        Nervous system
    7.3. Chronic toxicity
         7.3.1. Body weight, food and water intake

         7.3.2. Organ weights
         7.3.3. Pathology and histology
         7.3.4. Haematology and clinical chemistry
         7.3.5. Nervous system
         7.3.6. Kidney function
    7.4. Teratogenicity and embryotoxicity
    7.5. Mutagenicity
         7.5.1. Bacterial systems
         7.5.2. Yeast assays
         7.5.3.  Drosophila melanogaster
         7.5.4. Mammalian cell  in vitro assays
         7.5.5. Mammalian  in vivo assays
    7.6. Carcinogenicity


    8.1. Acrylonitrile
         8.1.1. Acute toxicity
        Inhalation exposure
        Dermal exposure
         8.1.2. Chronic toxicity - occupational exposure
        Clinical observations
        Other organs
        Nervous system
        Dermal effects
    8.2. Mutagenicity
    8.3. Carcinogenicity
    8.4. Simultaneous occupational exposure to acrylonitrile and 
         other chemicals
         8.4.1. Acute toxicity
         8.4.2. Chronic toxicity


    9.1. Sources and levels of exposure
    9.2. Acrylonitrile toxicity



    While every effort has been made to present information in 
the criteria documents as accurately as possible without unduly 
delaying their publication, mistakes might have occurred and are 
likely to occur in the future.  In the interest of all users of 
the environmental health criteria documents, readers are kindly 
requested to communicate any errors found to the Manager of the 
International Programme on Chemical Safety, World Health 
Organization, Geneva, Switzerland, in order that they may be 
included in corrigenda, which will appear in subsequent volumes. 

    In addition, experts in any particular field dealt with in 
the criteria documents are kindly requested to make available to 
the WHO Secretariat any important published information that may 
have inadvertently been omitted and which may change the 
evaluation of health risks from exposure to the environmental 
agent under examination, so that the information may be 
considered in the event of updating and re-evaluation of the 
conclusions contained in the criteria documents. 

                         *  *  *

    A detailed data profile and a legal file can be obtained from
the International Register of Potentially Toxic Chemicals, Palais
des Nations, 1211 Geneva 10, Switzerland (Telephone no. 988400 -



Dr I. Gut, Institute of Hygiene & Epidemiology, Prague,

Dr V.V. Ivanov, State Medical Institute, Krasnoyarsk, USSR

Dr J. Kopecky, Institute of Hygiene & Epidemiology, Prague,

Dr W.N. Rom, Rocky Mountain Center for Occupational &
   Environmental Health, School of Medicine, University of
   Utah, Salt Lake City, Utah, USA

Dr M. Sharratt, BP Group Occupational Health Centre,
   Sunbury-on-Thames, England  (Chairman)

Dr J. Sokal, Institute of Occupational Medicine, Lodz, Poland

Dr. L. Zisser, Department of Occupational Medicine, Kupat
   Holin - District Yehuda, Rehovoth, Israel  (Vice-Chairman)

 Representatives of other organizations

Dr A. Berlin, Health & Safety Directorate, Commission of the
   European Communities, Luxembourg

Dr R.A. Baxter, Monsanto Europe, Brussels (representing the
   Association of Plastic Manufacturers in Europe - APME)


Dr M.H. Draper, Medical Officer-Toxicologist, International
   Programme on Chemical Safety  (Secretary)

Dr K.W. Jager, Consultant, International Programme on Chemical


    Further to the recommendations of the Stockholm United 
Nations Conference on the Human Environment in 1972, and in 
response to a number of World Health Assembly resolutions 
(WHA23.60, WHA24.47, WHA25.58, WHA26.68) and the recommendations 
of the Governing Council of the United Nations Environment 
Programme, (UNEP/GC/10, July 3 1973), a programme on the 
integrated assessment of the health effects of environmental 
pollution was initiated in 1973.  The programme, known as the WHO 
Environmental Health Criteria Programme, has been implemented 
with the support of the Environment Fund of the United Nations 
Environment Programme.  In 1980, the Environmental Health 
Criteria Programme was incorporated into the International 
Programme on Chemical Safety (IPCS).  The result of the 
Environmental Health Criteria Programme is a series of criteria 

    The Institute of Hygiene and Epidemiology (Director, 
Professor Bohumir Rosicky), Prague, was responsible, as a Lead 
Institution of the IPCS, for the preparation of the first and 
second drafts, which were written and coordinated by Dr I. Gut 
and Dr J. Kopecky of that Institute. 

    The Task Group for the Environmental Health Criteria for 
Acrylonitrile met in Prague in the Institute of Hygiene and 
Epidemiology from 4-8 July 1983.  The meeting was opened by 
Professor B. Rosicky, and Dr M.H. Draper welcomed the 
participants and representatives of the organizations on behalf 
of the three organizations co-sponsoring the IPCS (UNEP/ILO/WHO).  
The Task Group reviewed and revised the second draft criteria 
document and made an evaluation of the health risks of exposure 
to acrylonitrile. 

    The efforts of all who helped in the preparation and the 
finalization of the document are gratefully acknowledged. 

                         * * *

    Partial financial support for the publication of this 
criteria document was kindly provided by the United States 
Department of Health and Human Services through a contract from 
the National Institute of Environmental Health Sciences, Research 
Triangle Park, North Carolina, USA - a WHO Collaborating Centre 
for Environmental Health Effects. 


1.1.  Summary

1.1.1.  Properties and analytical methods

    Acrylonitrile (CH2=CH-C-N) is a volatile, colourless, 
flammable liquid with a sweet characteristic odour.  It is used 
in the production of acrylic and modacrylic fibres, resins and 
rubbers, and as a chemical intermediate.  It has been employed as 
a fumigant.  Exposure to both the vapour and the liquid can occur 
at the workplace, the highest atmospheric concentrations 
occurring in acrylic fibre production. 

    For the control of exposure to acrylonitrile at the 
workplace, sampling should preferably be from the breathing zone 
of the worker; active and passive sampling techniques are 

    The most widely used analytical techniques are the gas 
chromatographic techniques; these are particularly sensitive if 
nitrogen-sensitive and specific sensors are used.  High-pressure 
liquid chromatographic, infra-red, and colorimetric methods may 
be useful, where gas chromatography is not available.  Methods 
have been developed for the determination of acrylonitrile in 
blood, food, water, etc.  Determination of acrylonitrile-derived 
mercapturic acids in urine may prove to be of value for the 
biological monitoring of exposure. 

1.1.2.  Sources of exposure

    Acrylonitrile is emitted from industrial plants in the form 
of vapours and in aqueous effluents; exposure of the population 
living near plants cannot therefore be excluded.  The total 
emissions from acrylonitrile plants have been estimated to be 
about 2.2% of total production, but these figures have decreased 
recently.  Polymers contain various concentrations of free 
acrylonitrile; when used for packaging in the food industry, 
minute amounts of the monomer may pass into the food.  
Acrylonitrile may also enter the environment accidentally, during 
its storage and transport. 

1.1.3.  Industrial and environmental levels of exposure

    Contamination of water and food is possible but, with the 
exception of the contamination of water supplies through 
accidental spillage, levels of exposure would be low.  The 
highest potential for exposure is at the workplace, both through 
inhalation of vapour and contamination of the skin by liquid 

1.1.4.  Monitoring of acrylonitrile uptake

    The most significant uptake of acrylonitrile vapour is 
through the respiratory tract.  Exposure is commonly monitored by 
determining the time-weighted average atmospheric concentrations. 

    Estimation of acrylonitrile-derived mercapturic acids in 
urine is a promising method for the biological monitoring of 
exposure, but further validating studies are needed. 

1.1.5.  Absorption, distribution, biotransformation, and 

    In animals, acrylonitrile is readily absorbed both through 
the skin and by inhalation.  Systemic and even fatal effects are 
possible via these routes. 

    The distribution of acrylonitrile within the animal body is 
fairly uniform.  There are no indications of accumulation in 
animal tissues following prolonged exposure. 

    At least 10 different metabolites of acrylonitrile have been 
identified.  Mercapturic acids are the major metabolites of 
acrylonitrile  in vivo.  Urinary excretion of acrylonitrile-
derived mercapturic acids is proportional to the internal 
concentration of acrylonitrile. 

    Elimination of acrylonitrile, as such, in expired air is 
negligible, but a small percentage is eliminated in the urine. 

1.1.6.  Effects on experimental animals

    Acrylonitrile induces a variety of toxic effects.  Effects 
due to over-exposure are non-specific and mainly related to the 
gastro-intestinal and respiratory tracts, the central nervous 
system, and the kidneys.  Respiratory distress, lethargy, 
convulsions, and coma occur with lethal or near-lethal exposures 
(7500 mg/m3, inhalation).  Dogs are most sensitive, and rats 
least sensitive to acrylonitrile, with mice, guinea-pigs, cats, 
and monkeys in an intermediate position.  However, the 
information available from these studies is too fragmentary to 
indicate clear no-observed-adverse-effect levels. 

    Extensive dermal exposure to the liquid may be lethal.  At 
lower exposures, irritation of the skin and mucous membranes can 

    The most typical biochemical changes caused by acrylonitrile 
are inhibition of sulfhydryl-dependent enzymes (lactate 
dehydrogenase, LDH (EC, sorbitol dehydrogenase, SDH (EC, pyruvate oxidase (EC and a reduction in the 
concentrations of glutathione and protein sulfhydryls in the 
blood and various organs, resulting in a disturbance of glucose 
utilization. The cyanide generated causes inhibition of 
cytochrome oxidase (EC but this seems to be of less 
significance than the above-mentioned metabolic disturbances, at 
low exposure levels. 

    Exposure to some organic solvents in addition to 
acrylonitrile may significantly enhance its toxic effects. 

    Acrylonitrile can cause embryotoxic and teratogenic effects, 
but only at levels near the toxic dose level for the specific 
experimental animal. 

    It is probable that acrylonitrile is not mutagenic itself, 
but that its metabolites are responsible for the positive effects 
in various test systems.  It is mutagenic in  in vitro systems 
(bacterial tests and cell cultures), but not in  in vivo systems, 
such as the dominant lethal assay. 

    On the basis of the results of several animal studies, using 
a wide dose-range, there is sufficient evidence to suggest that 
acrylonitrile is a carcinogen in the rat. 

1.1.7.  Effects on man

    Symptoms of over-exposure in man are non-specific.  They are 
related to the gastrointestinal and respiratory tracts, and to 
the central nervous system and include headache, insomnia, 
nausea, vomiting, diarrhoea, fatigue, mild jaundice, and 
irritation and inflammation of the respiratory tract and mucous 
membranes.  In more severe cases, unconsciousness and convulsions 
may occur.  Fatalities have been reported following exposure to 
acrylonitrile, especially following its use as a fumigant.  
Dermal exposure, especially to liquid acrylonitrile, may cause 
irritation, erythema, and blisters. Toxic and allergic dermatitis 
can occur. 

    While a correlation between exposure to acrylonitrile and the 
incidence of cancer in man has not been demonstrated conclusively 
in human epidemiological studies, the findings are not 
incompatible with this supposition.  Thus, there is no reason to 
disregard the evidence that has been provided by animal studies. 

    It follows that exposure to acrylonitrile should be kept as 
low as possible at the workplace and in the general environment, 
and that skin contact with liquid acrylonitrile should be 

1.2.  Recommendations for Further Research

    The Task Group noted that valuable information from industry, 
while available to national and international bodies, had not 
been published.  This greatly reduces the value of these studies, 
as they are unavailab1e for peer review and critical examination 
by the scientific community. 

    The Group recommended the following studies:

(a) Improvement and validation of passive sampling techniques
    with special attention to interfering substances;

(b) Validation of the measurement of acrylonitrile and
    acrylonitrile-derived mercapturic acids in urine as
    methods for biological monitoring for workplace exposure,
    with regard to analytical aspects and sampling conditions;

(c) Investigation of the environmental fate of acrylonitrile
    including photochemical degradation;

(d) Further investigation of the mechanisms of action and the
    nature of acute and chronic toxic effects in conditions
    relevant to human exposure;

(e) Studies on the carcinogenicity of acrylonitrile in
    relation to animal species other than the rat;

(f) Further investigation of the metabolism and toxicokinetics
    of acrylonitrile in different animal species, in order to
    obtain information that will assist in the interpretation
    of biological monitoring data in man;

(g) Further examination of the immunological aspects of the
    action of acrylonitrile in man and animals;

(h) Further studies on the effects of acrylonitrile on

(i) Investigations on reproductive outcome and mutagenicity in
    human beings occupationally exposed to acrylonitrile.

    Epidemiological data with good indications of past and 
present exposure levels should be available, to ensure an 
adequate health risk evaluation. 


2.1.  Physical and Chemical Properties of Acrylonitrile

2.1.1.  Physical properties

    Acrylonitrile (CH2=CH-C-N) is a volatile, colourless, 
flammable liquid with a sweet, characteristic odour.  It is 
slightly soluble in water and miscible with most organic solvents 
(American Cyanamid, 1959).  The vapours are explosive, cyanide 
gas being produced.  The explosive range in air at 25 C has a 
lower limit of 3.05%, and an upper limit of 17.0%, by volume 
(Patty, 1963).  The olfactory threshold level for acrylonitrile 
averages 40.4 mg/m3 (18.6 ppm) and ranges from 0.007 to 109.4 
mg/m3 (0.0031 to 50.4 ppm) (Baker, 1963). Important physical 
constants and properties of acrylonitrile are summarized in 
Table 1. 

2.1.2.  Chemical properties

        Structural formula:   H         H
                               \       /
                                \3   2/
                                 C = C
                                /     \
                               /       \  
                              H         C - N

         Synonyms:  cyanoethylene, 2-propenenitrile, vinyl

         CAS Registry Number: 107-13-1.

    The reactions of acrylonitrile involve the double bond (C=C) 
and/or the cyano group (CN) (American Cyanamid, 1959). It 
polymerizes to polyacrylonitrile, and copolymerizes with, e.g., 
styrene, butadiene, esters of acrylic or methacrylic acid, to 
form various resins, nitrile rubber, and acrylic and modacrylic 
fibres.  Hydration produces acrylamide or acrylic acid and 
esterification the corresponding acrylic esters. Reductive 
coupling produces adiponitrile.  With compounds containing active 
hydrogen(s) (AH molecules such as the biologically-important 
compounds containing the nucleophilic -CH, -NH, and -SH groups), 
cyanoethylation takes place: 

        A-H + CH2 = CH-CN  +  A-CH2CH2CN

(American Cyanamid, 1959).  This reaction is of particular
importance in relation to its fate in biological systems;
covalent binding of acrylonitrile to the tissue components has
been demonstrated (section  Direct oxidation of
acrylonitrile with hydroperoxide compounds affects the cyano
group of acrylonitrile, although in biological systems, it is

probable that oxidation of the double bond to the oxirane,
glycidonitrile (CH2 - CH-CN) occurs (Kopecky et al., 1980a,b).
                 \   /

Table 1.  Physical properties of acrylonitrilea 
appearance                          colourless liquid

boiling point                       77.3 C at 760 mm pressure

density                             0.8060 (20 C), 0.8004 (25 C)

flash point (tag open cup)          0 C
            (closed cup)            -4.4 C

freezing point                      -83.55,  0.05 C

ignition temperature                481 C

relative molecular mass             53.06

octanol/H2O partition coefficient   0.12b 

odour                               faintly pungent

refractive index                    nD 25  =  1.3888

% solubility in waterc              7.2%  (0 C)
                                    7.35% (20 C)
                                    7.9%  (40 C)

vapour pressure (mm Hg)             50    (8.7 C)
                                    100   (23.6 C)
                                    250   (45.5 C)
                                    500   (64.7 C)
                                    760   (77.3 C)

partial vapour pressure             log P = 7.518  -  1644.7
     water azeotrope                                      TK
                                    (i.e., 80 mm at 20 C)

Conversion factor for vapour        1 mg/m3 = 0.4605 ppm
     (25 C; 760 mm Hg)             1 ppm = 2.17 mg/m3 
                                    1 mg/litre water = 1 ppm
a  From: American Cyanamid (1959, 1974).
b  From: Dorigan et al. (1976); antilog of -0.92.
c  Acrylonitrile is miscible with most organic solvents.

    There have not been any experimental studies but, as a 
reactive olefine, it would be expected that acrylonitrile would 
be oxidized in the atmosphere under the influence of ultraviolet 
radiation (UVR) or by reactive oxygen species (atomic oxygen, OH 
radicals, ozone).  The atmospheric half-life of acrylonitrile is 
estimated to be 9-10 h (Suta, 1979). 

    Technical-grade acrylonitrile is more than 99% pure. Except 
for water, impurities and stabilizers are present at mg/kg levels 
only.  Possible contaminants are shown in Table 2.  Spontaneous 
explosive polymerization of pure acrylonitrile may occur, in the 
absence of oxygen, on exposure to visible light or alkali 
(DuPont, 1977).  A yellow colour may slowly develop on standing, 
particularly after excessive exposure to light.  Water improves 
the stability of acrylonitrile, and the technical-grade product 
is stabilized against self-polymerization and colour formation by 
the addition of hydroquinone monomethyl ether and water. 

2.2.  Analytical Methods

    In this section, sampling methods, sample storage, and 
analytical methods for determining acrylonitrile and its 
metabolites are discussed.  The only breakdown products 
considered are those detected  in vivo, as these are the only 
ones of importance for assessing levels of exposure to 

2.2.1.  Sampling methods

    Sorption tubes are widely used for sampling acrylonitrile in 
air, because samples can be taken over a prolonged period from 
the breathing zone of the worker.  The solid sorbent gas samplers 
have been critically reviewed by Crisp (1980).  Of the solid 
sorbents, activated charcoal, porous polymers, or silica gel are 
most commonly used.  Adsorbed acrylonitrile is later desorbed, 
generally by a solvent (methanol or carbon disulfide) or 
thermally, and determined by gas chromatography.  Several devices 
have been developed for sampling workplace air.  A sorbent 
sampling tube fastened to the worker's shoulder and a pump 
fastened to the belt may be worn for a whole working shift 
without discomfort.  Muhtarova (1977) described significant 
differences between the results of static sampling and personal 
monitoring in determining acrylonitrile exposure in workers.  
Personal monitoring gives a better indication.  Area 
concentrations can be determined by detector tubes, to give an 
immediate indication of the level (CIA, 1978; Grote et al., 

    In the widely-used NIOSH method S156 (NIOSH, 1976), a known 
volume of air is drawn through a charcoal tube (divided into 2 
sections in order to check that the adsorption capacity has not 
been swamped), and the charcoal is desorbed by methanol for 30 
min.  This method was validated by NIOSH over a concentration 
range of 17.5-70.0 mg/m3 (8.1-32.3 ppm) at 22 C and 760 mm Hg 
using a 20-litre sample; the coefficient of variation was 0.073.  
However, the suspicion that acrylonitrile may be a human 
carcinogen (NIOSH, 1978) led to the need to determine lower 
concentrations of acrylonitrile in air.  With a simple 
modification in method S156, using a desorbing solvent of 2% v/v 
acetone solution in carbon disulfide, Gagnon & Posner (1979) were 
able to achieve a sensitivity of 1.1 mg/m3 (0.5 ppm) based on an 
air sample volume of 15 litres.  The samples are stable for at 

least a week, even in the absence of a stabilizer.  A similar 
method, developed by the Midwest Research Institute for sampling 
air near acrylonitrile plants (Going et al., 1979), involves the 
use of charcoal tubes, sampling air at 1 litre/min, desorbing the 
sample with carbon disulfide, and analysing by gas 
chromatography.  However, high humidity and interference from 
other substances can reduce collection efficiency on charcoal; 
these problems can be overcome by the use of porous polymer 
absorbents and thermal desorption techniques (Campbell & Moore, 
1979; United Kingdom Health and Safety Executive, 1981). 

Table 2.  Specifications for acrylonitrile from two producersa 
Specifications                DuPont              Monsanto
acetone, mg/kg max.           n.r.b               300

acetonitrile, mg/kg max.      500                 500

aldehydes, as acetaldehyde     
mg/kg max.                    50                  50

iron, mg/kg max.              0.1                 0.2

hydrocyanic acid, mg/kg max.  10                  5

peroxides, as hydrogen
peroxide, mg/kg max.          0.3                 1.0

water, %                      2.5-4.5             2.5-4.5

inhibitor, MEHQc, mg/kg       35 - 50             35 - 50

acidity, as acetic acid,
mg/kg max.                    35                  20

pH, 5% aqueous solution       5.5-7.5             n.r.b 

non-volatile matter,
mg/kg max.                    100                 100

refractive index at 25 C     1.3880 - 1.3892     1.3880 - 1.3892

appearance                    clear & free        clear & free 
                              flowing             flowing
a  From: DuPont (1977) and Monsanto (1977a).
b  n.r. = not reported.
c  MEHQ - hydroquinone monomethyl ether (methylhydroquinone).

    While many industrial hygiene personal monitoring 
measurements have been carried out using these methods, over the 
last 3-4 years an increasing number of "passive" samplers (gas 
badges) (Silverstein, 1977) have been developed.  The advantages 
of these devices are that there are no moving parts to break 

down, regular flow calibration is unnecessary, and no bulky, 
expensive pumps are required. 

    Benson & Boyce (1981) and Benson et al. (1981) described a 
passive dosimeter in which acrylonitrile was adsorbed on a porous 
polymer (PorapakRN) contained in a removable element, and 
determined by thermal desorption gas chromatography.  It can be 
used satisfactorily for determining acrylonitrile concentrations 
in air under a range of atmospheric conditions, when working to 
a control limit of 8.7 mg/m3 (4 ppm) but, at a concentration of 
4.4 mg/m3 (2 ppm), a 40% error has been reported.  These devices 
are now considered to be as reliable as the more conventional 
pump and tube methods (Rose & Perkins, 1982). 

    The head-space sampling method is useful for the 
determination of residual acrylonitrile monomer in copolymers and 
by-products, since it is more sensitive (detection limit 1.1 
mg/m3 (0.5 ppm)) than direct injection (detection limit 21.7 
mg/m3 (10 ppm)) (Steichen, 1976).  It involves the equilibration 
of a solid polymer with air in a closed vessel. Free monomer is 
partitioned between the polymer phase and the "head-space" air, 
and the monomer concentration in the head-space is then 
determined (Steichen, 1976).  Oomens (1980) gives a detection 
limit for acrylonitrile of 0.02 mg/m3 (0.01 ppm) with the aid of 
a similar method, applying the more sensitive and specific PND 
detector.  The procedure has been used for determining the 
acrylonitrile monomer in copolymer solutions (McNeal & Breder, 
1981), plastic packaging, and beverages (Gawell, 1979).  Gawell's 
method is suitable for determining acrylonitrile at 
concentrations as low as 0.1 mg/kg, in plastics, and 0.005 mg/kg, 
in beverages.  The method has also been used for determining 
acrylonitrile in food-simulating solvents (US FDA, 1977a) and, 
with a detection limit of 0.5 mg/kg, in acrylonitrile-derived 
copolymers (Steichen, 1976). 

    Continuously recording gas chromatographic methods have been 
developed for monitoring atmospheric concentrations of 

    Samples of water containing acrylonitrile can be acidified by 
sulfuric acid to a pH < 4 and then kept at 0 C until analysed 
(Going et al., 1979). 

2.2.2.  Analytical methods for determinating acrylonitrile

    Acrylonitrile can be determined using instrumental methods: 
gas chromatography, possibly high-pressure liquid chromatography, 
infrared spectroscopy, polarography, and chemical titrimetric and 
colorimetric methods. 

(a)   Gas chromatography

    This is the most frequently used method for acrylonitrile 
determination, particularly in conjunction with the charcoal 
sampling method.  A number of gas chromatographic procedures have 

been developed for different types of samples.  Until recently, 
almost all involved flame ionization detection, but attention is 
now being paid to thermoionic nitrogen-selective detectors 
(Shevchik, 1976) in the determination of acrylonitrile (e.g., US 
FDA, 1977a; Gawell, 1979; McNeal & Breder, 1981). 

    Various column packings have been evaluated for the 
determination of acrylonitrile by gas chromatography, e.g., in 
the air (Parsons & Mitzner, 1975; Russell, 1975) (Table 3). 
Porous polymer column packings have the advantage of resolving 
acrylonitrile from methanol (frequently used to desorb 
acrylonitrile from charcoal) and of being useful for direct 
injection of aqueous acrylonitrile samples. 

    Examples of gas chromatographic methods for determining 
acrylonitrile in a variety of products and samples containing 
acrylonitrile are given in Table 4, together with the detection 

    Borg-Warner Chemicals (1977) developed a continuous-recording 
gas chromatograph that reportedly detects acrylonitrile below 1.1 
mg/m3 (0.5 ppm).  A portable gas chromatograph for the 
determination of acrylonitrile in air was developed by Vistron 
(personal communication, 1978) and a direct injection gas 
chromatograph for acrylonitrile determinations was tested by 
Union Carbide Corporation (1977); preliminary results indicate a 
detection limit below 2.2 mg/m3 (1 ppm). 

(b)   High-pressure liquid chromatography

    A high-pressure liquid chromatograph method has been 
developed for the determination of residual acrylonitrile monomer 
in acrylic polymer and fibre (US Consumer Product Safety 
Commission, 1978).  The acrylic polymer or fibre is heated above 
its glass transition temperature and refluxed continuously under 
water.  The extract is distilled and analysed.  No interference 
from contaminants has been noted. 

(c)   Infrared spectroscopy

    Direct determination of acrylonitrile in air by IR 
spectroscopy, using wavelength 10.49 m, 20 C and 760 mm Hg, and 
a 250 cm gas cell, has been reported to have a detection limit of 
about 0.5 ppm (v/v).  The equipment is expensive, requires skill 
to use, and is sensitive to physical damage.  A portable IR 
analyser for "on-the-spot" detection of acrylonitrile in air, 
with a detection limit of 0.4 mg/m3 (0.2 ppm), has been 
recommended by Jacobs & Syrjala (1978). 

Table 3.  Gas chromatographic conditions for acrylonitrile determination
Packing                   Conditions                    Comments                    Reference
Tenax                     80 C, 15 cc/min N2, -,       Used by American Cyanamid
                          60 x 0.3 cm, Teflon           for water analysis

0.4% Carbowax 1500 on     100 C, 30 cc/min He, -,      Head space analysis of      Steichen (1976)
Carbopax A                80 x 0.3 cm, stainless steel  residual monomer

Porapak Q, 50/80 mesh     155 C, 50 cc/min N2, -,      NIOSH method for acrylo-    NIOSH (1976)
                          120 x 0.6 cm stainless steel  nitrile in air

Porapak Q, 50/80 mesh     160 C, 30 cc/min N2,         Poor resolution from        Barrett (1974)
                          3.2 min, 150 x 0.3 cm         methanol
                          stainless steel

Porapak N, 50/80 mesh     170 C, 40 cc/min N2,         Resolved from methanol      Barrett (1974)
                          10.5 min, 270 x 0.3 cm
                          stainless steel

Chromosorb 101, 50/60 or  110 C to 200 C at           ASTM approved method for    ASTM (1981)
porous styrene divinyl    10 C/min, 25 ml/min He,      nitriles in water
benzene polymer           240 x 0.3 cm stainless

Porapak Q, 50/80 mesh     156 C, 50 cc/min He,         Used with a trapping        Bellar & Sigsby 
                          11.8 min, 360 x 0.3 cm        column for combustion       (1980)  
                          stainless steel               effluents

10% SP - 1000, 60/80      150 C, 45 cm/min             Acrylonitrile plus various  Marano et al. (1978)
mesh supelcopore                                        organic vapours
a  Column temperature, carrier gas and flow rate, retention time, column parameters.

Table 4.  Determination of acrylonitrile in different acrylonitrile-containing 
samples and products
Sample source                   Detection limit     Reference
water solution                  10 mg/kg            Ramstad & Nicholson (1982)

polyacrylonitrile               10 - 100 mg/kg      Reichle & Tengler (1968)

vinylidene chloride-            10 mg/kg            UK Ministry of Agriculture,  
acrylonitrile coated film                           Fisheries & Food (1982)

food samples                    0.01 - 0.02 mg/kg   UK Ministry of Agriculture, 
                                                    Fisheries & Food (1982)

acrylic co-polymers             0.5 mg/kg           Steichen (1976)
                                70  mg/kg           McNeal & Breder (1981)

carbonated beverage (simulated) 1 mg/kg             McNeal & Breder (1982)

fumigant residue in cereals &   0.1 mg/kg           Heuser & Scudmore (1969)
other foods 

air of acrylonitrile plants     n.s.                Cincolella et al. (1981)

acetone extract of styrene-     1 mg/kg             US Consumer Product Safety 
acrylonitrile resins                                Commission (1978)
n.s.  =  not stated

(d)  Polarography

    A polarographic method for the determination of acrylonitrile 
was first reported by Bird & Hale (1952).  Berck (1960) used the 
method of Daues & Hamner (1957) to determine acrylonitrile 
residues in walnuts.  Aqueous extracts of styrene-acrylonitrile 
copolymer (Petrova et al., 1972), the volatile fractions of 
styrene copolymer (Uhde & Koehler, 1967), and industrial waste 
water (Ponomarev et al., 1974) have also been analysed using 
polarography.  A method developed by Rogaczewska (1964) had a 
sensitivity of 10 mg/litre and 40 mg/m3 for the determination of 
acrylonitrile in solution and in air, respectively. 

(e)  Colorimetric methods

    In one method, the acrylonitrile-containing sample is 
hydrolysed by a strong base to ammonia, which is determined by 
the Nessler reagent (Rogaczewska, 1965; Aarato & Bittera, 1972).  
The detection limit of this method is about 6 mg/m3 (3 ppm) in 
air.  A modification using hypochlorite and sodium salicylate has 
a detection limit of 0.5 mg/m3 (Rogaczewska, 1976). 

    A modified hydrolytic method using hydrogen peroxide under 
acidic conditions has been developed for the determination of 
acrylonitrile in air (American Industrial Hygiene Association, 

1970; Maddock et al., 1977).  The sensitivity is in the range of 
20-300 g/ml of absorbing solution. 

    Another colorimetric method is based on the formation of 
cyanogen bromide under the influence of UVR and the production of 
a pink colour by coupling the cyanogen bromide with benzidine in 
pyridine solution.  Using this method, Kanai & Hashimoto (1965) 
determined acrylonitrile in the expired air, blood, and urine of 
exposed animals.  This method has been further used for the 
determination of acrylonitrile in air (Krynska, 1970; Tada, 1971; 
Russkih, 1972, 1973) with a detection limit of 0.4 - 0.5 mg/m3, 
and in food (Kroeller, 1970) and waste water (Ghersin et al., 
1969) with a detection limit of 2 mg/1itre.  When the sample 
contains both acrylonitrile and cyanide, the cyanide should be 
removed before analysis (Aldridge, 1944; Bruce et al., 1955; 
Kanai & Hashimoto, 1965). 

(f)  Titrimetric methods

    A titrimetric method based on the cyanoethylation of a 
sulfhydryl compound (lauryl mercaptan), by acrylonitrile, has 
been described (Haslam & Newlands, 1955).  An excess of the thiol 
is added to the acrylonitrile sample and, after the reaction, it 
is determined by iodometric or amperometric titration or by 
Ellman's reagent.  Although this method is specific, it is 
neither rapid nor sensitive enough. 

    A titrimetric method for determining acrylonitrile, developed 
by Terent'ev & Obtemperanskaya (1956), consists of the release of 
sodium hydroxide by the reaction of acrylonitrile with sodium 
sulfite.  A paper-strip modification of this method has recently 
been reported by Rajendran & Muthu (1981).  It is used for the 
detection of acrylonitrile in air and fumigated foodstuffs. 

(g)  Other analytical methods

    Other methods are not frequently used.  The 
spectrophotometric method of Hall & Stevens (1977), in which 
formation of a pyridine-acrylonitrile complex is determined at 
435.4 nm, suffers from interference from cyanide, which must be 
separated out of the solution.  Determination of acrylonitrile and its metabolites in
biological materials

(a)  Acrylonitrile in urine

    Sato et al. (1975) have modified the method of Aldridge 
(1944); acrylonitrile in urine is separated by azeotropic 
distillation and then determined by gas chromatography.  The 
detection limit is 5 g/litre. 

    More recently, Houthuijs et al. (1982) developed a method 
using head-space chromatography, which has a detection limit of 2 
g/litre.  Two millilitre aliquots of urine are equilibrated at 
90 C in 25 ml vials for 3-5 h; the vapour phase is injected 

automatically in a gas chromatograph, with a 15% carbowax column 
and a phosphor-nitrogen detector. 

(b)  Acrylonitrile metabolites in urine

    (i)  Acrylonitrile-derived mercapturic acids

    A gas-chromatographic method has been developed by Draminski 
& Trojanowska (in press) for the determination of 2-cyanoethyl-
mercapturic acid in the urine of workers exposed to acrylonitrile.  
The mercapturic acid is extracted from urine and derivatized by 
diazomethane to the methyl ester. The precision of this method is 
10% for 2-cyanoethyl-mercapturic acid in the concentration range 
of 50-350 mg/litre of urine. 

    A general procedure for determining the total amount of 
mercapturic acids (more generally the total amount of thioethers) 
in urine has been described by Seutter-Berlage et al. (1977, 
1978) and modified by Van Doorn et al. (1979) and Buffoni et al. 
(1982).  Deproteinized urine is hydrolysed with sodium hydroxide 
for 50 min at 100 C; this converts the mercapturic acids (and 
generally all thioethers) to the corresponding thiols.  After 
cooling and acidification, SH-groups are assayed by the method of 
Ellman (1959). 

    (ii)  Thiocyanate levels

    The colorimetric method (the formation of a coloured complex 
of thiocyanate with ferric ion) was developed in 1943 (Lawton et 
al., 1943). 

    Very recently, Imanari et al. (1982) applied the high-
performance liquid chromatographic technique, using a strong base 
ion-exchanger column for such determinations.  The method has 
been shown to differentiate well between the urinary thiocyanate 
levels found in smokers and non-smokers. 


3.1.  Natural Occurrence

    Acrylonitrile does not occur as a natural product.

3.2.  Industrial Technology, Production Data and Projection

    Current production is based on catalytic ammoxidation of
propylene in the vapour phase (Idol, 1974):

2CH2 = CH-CH3 + 2 NH3 + 3 O2 -------> 2 CH2 = CH-CN + 6 H2O

Bismuth phosphomolybdate is the most frequently used catalyst.  
The chief by-products are acetonitrile and hydrogen cyanide.  
Processes previously used in the production of acrylonitrile 
were:  (i) the catalytic addition of hydrogen cyanide to 
acetylene; (ii) the catalytic dehydration of ethylene to 
cyanohydrin; and  (iii) the catalytic reaction of propylene with 
nitric oxide.  These processes are no longer used by the major 
manufacturers in the world. 

    In 1976, the known production of acrylonitrile was about 2.4 
million tonnes (IARC, 1979).  US manufacturers produced 0.69 
million tonnes, Western European manufacturers, 0.92 million 
tonnes, and Japanese manufacturers, 0.63 million tonnes.  
Production figures for East European countries and the USSR are 
not available. 

    The average annual growth of acrylonitrile production was 
about 11% during 1965-1975 (Anonymous, 1977).  While further 
growth was expected during the early 1980s, because of increased 
demands for polyacrylamide in tertiary oil recovery (Pujado et 
al., 1977), this did not occur owing to a general recession in 
world trade.  The West European figure for 1981 is of the order 
of 800 000 tonnes (Personal communication), approximately 15% 
less than in 1976. 

3.3.  Use Patterns

    The use pattern for acrylonitrile and its products in the USA 
in 1976 and Western Europe in 1977 are presented in Table 5 
(IARC, 1979). 

    In a mixture with carbon tetrachloride, acrylonitrile has 
also been used as a fumigant for tobacco (Berg, ed., 1977) and 
for flour milling and bakery equipment. 

Table 5.  The use patterns of acrylonitrile and its products in the
USA (1976) and Western Europe (1977)a 
Product                % of               % of product production
                       USA  W. Europe

acrylic and            48   68            82 - clothing and home
modacrylic fibres                              furnishings
                                          18 - export

acrylonitrile-         21   15            88 - pipe fittings, automotive
butadiene-styrene and                          vehicle components, etc.
acrylonitrile-styrene                     12 - automobile instrument
resins                                         panels, household items

adiponitrile           12   --            mainly hexamethylenediamine

other products         19   17            21 - nitrile elastomers
                                          21 - acrylamide
                                          16 - barrier resins
                                          42 - polyether polymer
                                               polyols, fatty diamines,
a  From:  IARC (1979).

    Pesticides containing acrylonitrile have been withdrawn by 
the manufacturers.  Acrylonitrile polymers and copolymers are 
components of products intended for use in contact with food, 
e.g., (i) vinyl resin coatings; (ii) adhesives; (iii) 
cellophane; (iv) paper and paperboard components (limited); (v) 
polyolefin films; (vi) elastomers - for repeated use; and (vii) 
rigid, semi-rigid, and modified acrylic and vinyl plastics.  In 
the USA, the amount of acrylic component may not exceed that 
which is reasonably required to produce the intended effect (US 
FDA, 1977b). 

    The acrylonitrile content of containers fabricated from 
acrylonitrile copolymers and the possible migration of 
acrylonitrile into foods and beverages have been reviewed (US 
FDA, 1977a).  The use of copolymers of acrylonitrile for making 
beverage bottles was banned in the USA in September, 1977. 

    The Canada Food and Drugs Act and Regulations (1982) prohibit 
the sale of any food in packaging containing acrylonitrile, such 
that the compound may pass into the food. 

    Table 6 shows the levels of residual acrylonitrile in several 
polymers, some acrylonitrile derivatives, and products fumigated 
with acrylonitrile (US Consumer Product Safety Commission, 1978). 

Table 6.  Levels of residual acrylonitrile found in various 
Product                                 Acrylonitrile   
acrylic and modacrylic fibres           1 mg/kga 

acrylonitrile-butadiene-styrene resins  30-50 mg/kga 

styrene-acrylonitrile resins            15 mg/kga 

nitrile rubber and latex material       0-750 mg/kga 

acrylamide                              25-50 mg/kga 

polyether polymer polyols               100-300 mg/kga 

shelled walnuts                         0-8.5 mg/kgb 

US cigarettes (non-filtered)           1-2 mg/100 cigarettesc 
a   From: US Consumer Product Safety Commission (1978).
b   38 days after fumigation with a mixture of acrylonitrile 
    and carbon tetrachloride (Berck, 1960).
c   From: Burin et al. (1974); Wynder & Hoffmann (1967).

    The total emissions from acrylonitrile plants in the USA, in 
1974, have been estimated to be about 2.2% of the total 
production (Table 7) (Patterson et al., 1976).  More recent 
estimates (Suta, personal communication, 1982), following the 
introduction of stricter emission controls, indicate an overall 
reduction in emissions and a change in pattern (for 1981, 800 
tonnes for acrylonitrile production and 3000 tonnes for end-
product manufacture). 

3.4.  Disposal of Wastes

    Acrylonitrile may also enter the environment during storage, 
transport, transfer, and end-use.  A detailed study on the entry 
of acrylonitrile into the environment was carried out by the 
Midwest Research Institute for the EPA (Going et al., 1979).  
Air, water, and soil were sampled at, and near to, acrylonitrile 
and acrylamide production plants and acrylonitrile-derived resin, 
fibre, and elastomer production plants. 

    During acrylonitrile production, the fo1lowing wastes are 
produced:  gaseous wastes; liquid wastes (waste water column 
bottoms, acetonitrile column bottoms, heavy ends, crude 
acetonitrile, hydrogen cyanide); and solid wastes (catalyst fines 
and organic polymers).  Three types of on-site disposal methods 
have been described by Hughes & Horn (1977): (a) flare; (b) 
thermal incineration; and (c) deep-well pond and deep-well 

Table 7.  Acrylonitrile emissions from plants 
in the USA in 1974a 
Source                        Emission (tonnes)
acrylonitrile production      6400

end-product manufacture       5900

bulk storage                  1800

total emission                14 100
a  From: Patterson et al. (1976).

    Much liquid waste from acrylonitrile-manufacturing plants is 
discharged directly into deep wells, after pre-treatment using 
alkaline hydrolysis, the biodegradable effluent being disposed of 
in publicly-owned treatment works.  In some cases, organic wastes 
are incinerated (Lowenbach et al., 1978). 

    Deep-well injection is no longer considered a viable method 
in the USA; to control the drilling of new wells, an industrial 
discharger must re-apply for a permit (US EPA, 1977). 

    Lowenbach et al. (1978) extensively reviewed the alternative 
biological, chemical, and physical methods of treating waste 
waters from acrylonitrile manufacture, but a detailed discussion 
of these is not within the scope of this report. 

3.5.  Accidental Release

    Acrylonitrile may be released accidentally into the 
environment.  Its half-life in air is estimated to be 9-10 h 
(section 2.1.2).  In water, the half-life, as estimated by the 
BOD test, is 5-7 days.  Although these data would indicate that 
small spillages would not present a problem, initial high levels 
of acrylonitrile may have severe local effects.  No 
bioaccumulation or food chain concentration potential has been 
noted (US Dept of Transportation, 1974), but it was observed that 
the concentration of acylonitrile in the ground water increased 
when it rained several months after an accidental spillage 
occurred.  The persistence of acrylonitrile in the water of wells 
located within 30 m of a spill of 91 000 litres of acrylonitrile 
from a tank car was followed for about 1 year (Miller & Villaume, 
1978).  No attempt was made to contain or clean up the spill for 
108 days and water from 5 wells showed acrylonitrile 
concentrations ranging from 46 up to 3520 mg/litre during this 
time.  On day 108, contaminated soil was removed, but levels of 
acrylonitrile actually increased in some wells.  Levels decreased 
after about 170 days, when contaminated ground water was pumped 
away; a sample of this ground water contained an acrylonitrile 
concentration of 144 mg/litre.  It is possible that the high 
concentration of acrylonitrile produced by the spill was lethal 
to bacteria, precluding biological degradation.  However, no 
quantitative measurements of soil or water organisms were made. 

3.6.  Environmental Persistence

    Acrylonitrile is readily degraded by acclimated anaerobic 
microorganisms (Mills & Stack, 1955).  Aerobic degradation with 
activated sludge is complete in 20 days (Miller & Villaume, 1978; 
Freeman et al., 1981).  The residual level after aerated 
activated sludge treatment was below 0.1 mg/kg. Acrylonitrile has 
been shown to inhibit anaerobic organisms (For fish toxicity, see 
Table 11). 


4.1.  Exposure of the General Population

4.1.1.  Air

    The possibility of exposure to acrylonitrile-contaminated air 
is limited to residents near industrial production and processing 
sites.  In the vicinity of 2 plants producing acrylonitrile, high 
concentrations of the monomer, ranging from 390 to 608 mg/m3 
(180-280 ppm) were found near the exhausts of both ships and 
storage tanks (Sato et al., 1979). Going et al. (1979) determined 
acrylonitrile concentrations in samples of air, soil, water, and 
sediments around 11 industrial sites.  The concentrations of 
acrylonitrile in air varied from < 0.1 - 325 g/m3 ; the highest 
levels were found at an acrylonitrile-, butadiene-styrene resin 
plant and an acrylonitrile/acrylamide plant.  The occurrence of 
acrylonitrile was highly correlated with the wind patterns; the 
highest levels were found downwind of the plant or at points 
crosswind but close to the plant.  The air also contained 
xylenes, ethylbenzene, dichlorobenzenes, toluene, 
trimethylbenzenes, and styrene. 

4.1.2.  Water

    Acrylonitrile was present in effluent discharged from 
chemical and latex manufacturing plants (Shackelford & Keith, 
1976), and was detected at 0.1 g/litre in effluent discharged 
from an acrylic fibre-manufacturing plant in the USA (Europ-Cost, 
1976).  Near 11 industrial sites (Going et al., 1979), the 
highest acrylonitrile levels in water were 3.5 and 4.3 mg/litre 
from an acrylic/modacrylic fibre plant and a nitrile elastomer 
plant, respectively.  There was no apparent correlation between 
air levels and water concentrations.  No acrylonitrile was found 
in the soil and sediments.  Water samples from some plants also 
contained propionitrile. 

4.1.3.  Food

    Contamination of food from polymer packaging material 
containing free acrylonitrile has been reported.  Following a 
study on the migration of acrylonitrile from ABS and AS resins, 
Tatsuno et al. (1979) concluded that after long-term preservation 
of food in ABS and AS resins the concentration of acrylonitrile 
in food may rise to 0.05 mg/kg.  Further studies on food-
simulating solvents showed that migration of acrylonitrile 
occurred from ABS and AS resins into 4% acetic acid, 20% ethanol, 
heptane, and olive oil; it was concluded that resins containing 
acrylonitrile levels of more than 10 mg/kg should not be used for 
packaging foods containing alcohol (Tatsuno et al., 1980).  
Nitrile resins made from copolymers of acrylonitrile and other 
monomers (e.g., methyl acrylate) are no longer used in the USA to 
make beverage bottles (US FDA, 1977a).  In a study performed in 
Sweden, the amount of acrylonitrile monomer found in nitrile 
resin bottles was 2-5 mg/kg.  The amount in the beverage was 

generally 0.002 - 0.003 mg/kg, but two samples contained as much 
as 0.009 mg/kg (Vaz, 1981, personal communication).  A government 
survey of the acrylonitrile content of food suggested that the 
average intake of acrylonitrile in the United Kingdom was likely 
to be less than 0.3 g/person per day (United Kingdom Ministry of 
Agriculture, Fisheries & Food, 1982). 

    An acrylonitrile concentration of 0-19 mg/kg was detected in 
dry food fumigated with acrylonitrile at a concentration of 10 
g/m3 .  The study was carried out using radioactive acrylonitrile 
and provided information that acrylonitrile levels in the stored 
food decreased by 30-70% over a period of 2 months (Pfeilsticker 
et al., 1977). 

4.1.4.  Other sources of exposure

    Free acrylonitrile monomer has been found in commercial 
acrylonitrile polymers at levels of less than 1 mg/kg (acrylic 
and modacrylic fibres), 15 mg/kg (styrene-acrylonitrile resins), 
30-50 mg/kg (ABS resins) and 0-750 mg/kg (nitrile rubbers and 
latex materials) (US Consumer Product Safety Commission, 1978). 

    Another possible source of acrylonitrile environmental 
exposure is accidental spillage during transport.  The following 
estimates have been made of the incidence of the accidental 
release of acrylonitrile per year: during transport in barges - 
0.0117; in trucks - 0.063; and by rail - 0.17 (Miller & Villaume, 
1978).  This means, for example, that during transport by rail, 
one accident would occur approximately every 6 years. 

4.2.  Occupational Exposure

    Up to 12 000 workers in the USA were thought to have come 
into major contact with acrylonitrile during 1976 and possibly 
some 125 000 workers were exposed, to some extent (Miller & 
Villaume, 1978).  It has also been estimated that as many as 
400 000 may have had some contact with acrylonitrile in 1976. 
The exposures reported in several countries are shown in Table 8. 

    The introduction of a lower exposure limit in several
countries is likely to have decreased the actual exposure to
acrylonitrile at the workplace.

    As acrylonitrile vapour is twice as dense as air, spills
and leaks in enclosed buildings may lead to harmful
accumulations of vapour, especially in low-lying areas
(Baxter, 1979).  The same author describes various
possibilities for preventing this, such as the use of double
mechanical seals, enclosed drainage systems, well-ventilated
sampling points, etc.  Plant design should aim at complete
containment of acrylonitrile, both as a liquid and a vapour.

Table 8.  Concentration of acrylonitrile in the air at work-places
Operation                    Acrylonitrile in            Reference
                             work-place air (mg/m3)
                             Average level  Range
Acrylonitrile production     5 - 0.5b       -            Zotova (1975a)
  during loading (open air) 5              0.2 - 60     Cincolella et al. (1981)
  near ACN tanks or pumps    45             4 - 125      Cincolella et al. (1981)
                             -              4.2 - 7.2    Gincheva et al. (1977)

Acrylic fibre production                    3 - 20       Orusev et al. (1973)
                             -              <11          Enikeeva et al. (1976)
                             -              <11          Sakurai & Kusumota (1972)
                             -              <45
                             4.6 - 31a,s    <2.2 - >43   Sakurai et al. (1978)
                             0.2 - 9.1a,t   -

  polymerization             8              <4 - >20     Czajkowska et al. (1969)
                             <4             <1 - >10     Lodz Sanit. Inspec. Survey (1981)
                             25             2 - 103      Cincolella et al. (1981)

  spinning                   6              1.5 - 20     Czajkowska et al. (1969)
                             <4             <1 - >10     Lodz Sanit. Inspec. Survey (1981)
                             9.5                         Sakurai et al. (1978)

Thermosetting plastic plant  1.4                         Scupakas (1968)

Rubber footwear plant                       1 - 11       Volkova & Bagdinov (1969)

Unspecified chemical         0.6 - 6                     Babanov et al. (1959)

Production of acryl-         4a,s,t         0 - 22       Iwasaki et al. (1980)
butadiene-styrene resin 

  polymerization             30             0 - 200      Cincolella et al. (1981)

Production of nitrile rubber

  rubber - polymerization    4              1 - 27       Cincolella et al. (1981)

  reactor cleaning           36t            5 - 54       Cincolella et al. (1981)

Acrylic dispersions          78             9 - 600      Cincolella et al. (1981)
(Latex production 
a  2 or more factories evaluated.
b  average levels over 5 years.
t  time-weighted average concentration.
s  spot.
    A code of practice has recently been published for the safe 
design, construction, and use of plants (CIA, 1978). Safe 
handling, engineering, and work practices, controls, compliance 
programmes, personal protective equipment, housekeeping, employee 
information and training, signs and labels, etc. for work with 
acrylonitrile have been described by the OSHA (1981). 

    Exposure to acrylonitrile may also occur through skin 
contact.  Acrylonitrile was shown to contaminate the skin of 
workers, their clothing and tools, also the equipment, walls, 
windows, handrails, handles, etc. in the workplace and was not 
easy to remove.  A protective paste of household soap, mineral 
oil, glycerine, and china clay was said to reduce contamination 
of the palms of the hands by 67% (Zotova, 1975a). 

    Acrylonitrile can penetrate clothing and leather shoes 
(American Cyanamid, 1976).  Dermal contact with liquid 
acrylonitrile may cause local skin damage, severe dermatitis, and 
systemic toxicity, and must therefore be prevented by high 
standards of industrial hygiene. 

4.3.  Estimate of Human Exposure from All Environmental Media

    The production and use of acrylonitrile at the workplace 
provide the greatest potential for exposure.  Airborne exposure 
to acrylonitrile near industrial sites appears to pose the 
highest potential risk for the general population; the potential 
for exposure through water and food appears to be low by 


5.1.  Absorption

5.1.1.  Human studies  Uptake through inhalation

    The retention of acrylonitrile in the respiratory tract in 3 
volunteers exposed to a concentration of 20 mg/m3 for up to 4 h 
was 46  1.6% and did not change throughout the inhalation period 
(Rogaczewska & Piotrowski, 1968).  Dermal absorption

    Rogaczewska & Piotrowski (1968) applied liquid acrylonitrile 
to the forearm skin of 4 human volunteers and estimated that the 
average absorption rate was 0.6 mg/cm2 per h.  Uptake by other routes

    No data avai1able.

5.1.2.  Experimental animal studies  Uptake through inhalation

    Young et al. (1977) determined the recovery of 14C 
acrylonitrile in rats exposed to 11 or 220 mg/m3 (5 or 100 ppm) 
for 6 h in a "nose only" inhalation chamber.  In the first 9 days 
following the start of inhalation, 82.2% of the radioactivity was 
recovered from the urine, after the higher dose, and 68.5%, after 
the lower dose, 3-4% occurred in the faeces; and 6% and 2.6%, 
respectively, were expired as 14CO2.  Dermal absorption

    Three rabbits breathing pure air while their skin (315-350 
cm2 ) was exposed to an atmosphere containing an acrylonitrile 
concentration of 1-4.2 g/m3, survived, whereas 3 other rabbits 
breathing pure air with the skin exposed to 44-62 g/m3 died 
within 2.5-4 h.  Inhalation exposure to 0.58-0.67 g/m3 was fatal 
for 3 rabbits within 2-3 h (Rogaczcwska, 1975).  The author 
interprets these data as suggesting that dermal absorption of 
vapour is about 100 times less efficient than its pulmonary 
absorption.  The immersion of rabbit ear in liquid acrylonitrile 
was fatal for the animal within a few hours (Rogaczewska, 1971). 

    Subcutaneous (sc) or intravenous (iv) administration of
14C-acrylonitrile at 0.5 mmole/kg body weight to rats resulted
in faster and greater elimination of radioactivity in the first 4 
h than after oral administration (Gut et al., 1980).  Uptake by other routes

    Young et al. (1977) calculated that after oral administration 
of 0.1 mg or 10 mg of 14C-acrylonitrile per kg body weight, 85-
100% of acrylonitrile was absorbed in rats. The absorption rate 
was lower in rats after oral administration than after sc or ip 
administration (Nerudova et al., 1980a; Gut et al., 1981).  After 
ip administration, the blood concentration of acrylonitrile 
reached a maximum in several minutes and then decreased rapidly 
(Nerudova et al., 1980a; Gut et al., 1981).  After ip and oral 
administration of 1,2-14C acrylonitrile and acrylo14C-nitrile to 
rats, 82-93% of the radioactivity was recovered from the urine 
and some 3-7% exhaled unchanged in the breath in 24 h (Sapota, 

5.2.  Distribution and Toxicokinetics

5.2.1.  Human studies

    No data available.

5.2.2.  Experimental animal studies

    Acrylonitrile concentrations in blood and liver reach higher 
levels after iv or ip administration than after oral 
administration; concentrations rapidly decrease in blood (t0.5 = 
19 min) and liver (t0.5 = 15 min after iv and 21 min after ip 
administration) (Nerudova et al., 1980a; Gut et al., 1981).  The 
apparent t0.5 after oral administration is 61 min in blood and 70 
min in liver, but this appears to be due to slow absorption 
rather than to slow elimination.  The area under the acrylonitrile 
concentration/time curve for blood was higher than for liver 
after oral, iv, or ip administration (Gut et al., 1981), 
indicating rapid transformation of acrylonitrile by the liver.  
Extrapolation of acrylonitrile blood levels after ip or iv 
administration in rats to zero time indicated that the apparent 
volume of distribution was unity, and that concentrations of free 
acrylonitrile in the rest of the body were unlikely to be greater 
than that in the blood (Nerudova et al., 1980a). 

    Young et al. (1977) followed the distribution of 
radioactivity in rats after a single oral or iv dose of 14 C-
acrylonitrile.  Radioactivity was found in the lung, liver, 
kidney, stomach, intestines, skeletal muscle, blood, and other 
organs and tissues, but high levels of radioactivity occurred in 
erythrocytes, skin, and stomach regardless of the dose and route.  
The high levels in the stomach wall after iv administration 
support the observation of Nerudova et al. (1980a) that, after iv 
administration, acrylonitrile is excreted into the stomach lumen. 

    After single intraperitoneal and oral administration to
rats of 1,2-14C acrylonitrile and acrylo14C-nitrile, most of
the 14C found in the tissues was associated with erythrocytes,
liver, and kidneys, lower levels being found in the lung and

brain.  The 14C in the erythrocytes was still largely retained
48 h after administration.  Significant differences in the
rates of 14C loss from tissues occurred with 1,2-14C
acrylonitrile and acrylo14C-nitrile given orally (Sapota &
Draminski, 1981; Sapota, 1982).

    After oral administration to rats, up to a maximum of 94%
of 14C from 1-14C acrylonitrile in erythrocytes was found to
be covalently bound to cytoplasmic and membrane proteins, whereas 
90% of the radioactivity from potassium cyanide in erythrocytes 
was found in the haem fraction of haemoglobin (Farooqui & Ahmed, 

    After a single ip injection of 2,3-14C acrylonitrile in
male rats, radioactivity was generally highest in the blood, 
intermediate in the spleen, liver, and kidney, and lower in other 
tissues.  The percentage of the dose remaining in the body after 
9 days was estimated to be about 5% of the administered dose 
(Hashimoto & Kimura, 1977). 

    A semi-quantitative study using whole-body autoradiography 
(Sandberg & Slanina, 1980) confirmed that, after iv 
administration to rats, acrylonitrile and/or its metabolites 
accumulate in the blood, liver, kidney, stomach mucosa, adrenal 
cortex, intestinal contents, and hair follicles of rats.  After 
oral administration to the monkey (Sandberg & Slanina, 1980), 
high radioactivity levels were detected in the liver, kidney, 
intestinal mucosa, adrenal cortex, and blood. As total 
radioactivity was measured in the studies of Young et al. (1977), 
Sandberg & Slanina (1980), and Sapota & Draminski (1981), it was 
impossible to differentiate acrylonitrile from its metabolites or 
from acrylonitrile bound covalently to proteins (Bolt et al., 
1978; Gut et al., 1981); thus, these studies are difficult to 
interpret from the point of view of the chemobiokinetics of free 

    Peter & Bolt (1981) found that 12 h after ip or iv 
administration of 2,3-14C acrylonitrile, about half of the 
radioactivity remaining in the tissues was irreversibly bound to 
proteins.  The rapid elimination of acrylonitrile mercapturic 
acid after iv, ip, or sc administration (Gut et al., 1981a) 
indicates that most of the acrylonitrile-derived radioactivity in 
the distribution studies was associated with cyanoethylglutathione, 
or subsequent intermediate metabolites including acrylonitrile 
mercapturic acid. 

    Thus, it is impossible to determine conclusively from the 
present data whether the relatively high levels of acrylonitrile-
14C radioactivity in the erythrocytes, kidney, spleen, liver, 
adrenals, stomach walls, and skin are due to free acrylonitrile, 
its metabolites, or cyanoethylated proteins.  However, the 
chemobiokinetics of free acrylonitrile in blood and liver (Nerudova 
et al., 1981) suggest that its distribution is fairly uniform and 
that higher levels of radioactivity in some organs and erythrocytes 
are due to reaction products of acrylonitrile with soluble and 
protein sulfhydryls. 

    Information on the subcellular distribution of 1,14C
acrylonitrile in rat can be found in Ahmed et al. (1982). Sato et 
al. (1982) studied the distribution and accumulation of 2,3-14C 
acrylonitrile in the rat.  They observed a longer retention of 
acrylonitrile in brain and muscle.  The cytosol fractions of brain, 
liver, and kidney showed a relatively high specific radioactivity. 

    The evidence, available at present, on the distribution of 
acrylonitrile in the body, and on tissue damage following exposure, 
does not indicate increased accumulation in any particular tissue 
or organ, except erythrocytes, and there is no indication from 
animal studies of tissue accumulation following long-term exposure. 

5.3.  Biotransformation and Elimination

    Levels of acrylonitrile metabolites in blood and their 
relationship to atmospheric acrylonitrile concentrations or to the 
dose administered are usually considered together, in studies on 
the relationship between the dose or concentration of acrylonitrile 
and the elimination of metabolites in urine. They will therefore be 
considered together in the following section. 

5.3.1.  Human studies

    Acrylonitrile is metabolized partly to thiocyanate.  Blood 
thiocyanate levels of volunteers exposed to acrylonitrile 
concentrations below 45 mg/m3 (22 ppm) for 30 min returned to normal 
after 24 h, while elevated levels were still present 12 h after 
exposure to 110 mg/m3 (50 ppm) for 30 min (Wilson & McCormick, 

    Draminski & Trojanowska (in press) reported that at airborne 
acrylonitrile concentrations of between 3 and 10 mg/m3, 
concentrations of  S-(2-cyanoethyl) mercapturic acid in the urine of 
13 workers exposed to acrylonitrile, fell in the range of 50-200 

5.3.2.  Experimental animal studies

    Acrylonitrile is partly metabolized to cyanide, which is then 
transformed by rhodanese (EC to thiocyanate and eliminated 
in urine (Dudley & Neal, 1942; Brieger et al., 1952; Ghiringhelli, 
1954).  However, the fate of the major portion of administered 
acrylonitrile was not clear until recently.  Recent studies have 
shown that the major urinary metabolites in rats, hamsters, guinea-
pigs, rabbits, and dogs are mercapturic acids resulting from the 
glutathione-S-transferase(s) (EC -catalysed conjugation 
of acrylonitrile or glycidonitrile with glutathione (section  At present, at least 10 acrylonitrile metabolites have 
been isolated and/or identified in animal urine. 

    The oxidative pathway leads to the liberation of cyanide via an 
epoxide (glycidonitrile) and cyanohydrin (Kopecky et al., 1980a,b).  
Cyanohydrin spontaneously decomposes to cyanide and glycolaldehyde 
which, together with 2-cyanoethanol, cyanoacetic acid, and acetic 

acid, have been found as  in vitro metabolites of acrylonitrile 
(Duverger-van Bogaert et al., 1981).  Only 2-cyanoethanol and 
cyanoacetic acid were detected in the urine of rats administered 
acrylonitri1e intraperitoneally (Lambotte-Vandepaer et al., 1981a).  
The proposed routes of the oxidative pathway are shown 
diagrammatically in Fig. 1; some of the biotransformation steps are 

    The existence of a glucuronoconjugate of acrylonitrile was
reported in the urine of rats after oral administration of
acrylonitrile (Hoffman et al., 1976).  Two metabolites of
acrylonitrile ( S-[2-cyanoethyl] cysteine and  S-[2-cyanoethyl]
mercapturic acid) were identified by Dahm (1977) in rats given
radiolabelled acrylonitrile, but he was unable to identify a
third metabolite, as it was unstable.  Young et al. (1977)
found that acrylamide was not a metabolite as had been
suggested by Hashimoto & Kanai (1965).  The same authors also
identified carbon dioxide as a metabolite in rats, but they
were unable to detect significant quantities of free
acrylonitrile or cyanide in the urine of exposed rats, though
Hashimoto & Kanai (1965) estimated that 15% of an iv dose of
acrylonitrile was eliminated unchanged in the urine and
expired air of the rabbit.

FIGURE 1  The oxidative pathway of acrylonitrile metabolism

    The oxidative pathway of acrylonitrile biotransformation 
includes a number of consecutive enzyme-catalyzed or spontaneous 
reactions.  The first step, oxidation of acrylonitrile to 
glycidonitrile, is catalyzed by hepatic microsomal mono-oxygenases 
(Abreu & Ahmed 1980; Kopecky et al., 1980a,b; Guengerich et al., 
1981; Ahmed & Abreu, 1982). Glycidonitrile is a reactive 

intermediate, and a number of its metabolites have been recorded; 
in  in vitro experiments it is transformed by epoxide hydrolase (EC to glycolaldehyde cyanohydrin, which decomposes 
spontaneously to hydrocyanic acid (cyanide) and glycoealdehyde 
(Kopecky et al., 1979, 1980a,b; Abreu & Ahmed, 1980; Duverger-van 
Bogaert, 1981a).  The yield of cyanide in the  in vitro experiments 
depends on the techniques used (Nerudova et al., 1980b). Besides 
forming conjugation products with glutathione (section, 
glycidonitrile rearranges to cyanoacetaldehyde, which is further 
reduced to 2-cyanoethanol or oxidized to cyanoacetic acid.  Acetic 
acid is also present (Duverger-van Bogaert, 1981). 

    The results of animal studies have shown that cyanide formed  in 
 vivo is subsequently converted by rhodanese (EC to 
thiocyanate and eliminated in urine (e.g., Dudley & Neal, 1942; 
Brieger et al., 1952; Ahmed & Patel, 1981). Thiocyanate has been 
directly measured in the urine of various animals after 
acrylonitrile administration (Lawton et al., 1943; Mallette, 1943; 
Czajkowska, 1971; Efremov, 1976b).  Rats administered acrylonitrile 
at 60 mg/kg body weight, excreted thiocyanate in the urine at a 
constant rate of 0.53 mg/h with an excretion half period of 13 h 
(Czajkowska, 1971). Sulfhydryl compounds (cysteine, BAL, and 
Unithiol) increase the activity of rhodanese in the conversion of 
cyanide to thiocyanate  in vitro, as well as  in vivo (e.g., 
Frankenberg, 1980).  A similar increase with acrylonitrile has not 
been convincingly demonstrated (Gut et al., 1975), perhaps because 
of the inhibiting properties of acrylonitrile on rhodanese.  Mercapturic acids formed in acrylonitrile biotransformation 

    Cyanoethylation of naturally-occurring sulfhydryl compounds 
plays an important role in acrylonitrile metabolism.  Acrylonitrile 
forms stable conjugates with L-cysteine and L-glutathione  in vitro 
(Hashimoto & Kanai, 1965; Gut et al., 1975) and a portion of 
absorbed acrylonitrile is thus prevented from being metabolized to 
cyanide.  Depressed levels of sulfhydryl compounds have been 
reported following acrylonitrile administration (e.g., Wisniewska-
Knypl et al., 1970; Hashimoto & Kanai, 1972; Vainio & Mkinen, 
1977; Dinu & Klein, 1976; Szabo et al., 1977).  The spontaneous 
conjugation of glutathione with acrylonitrile or glycidonitrile 
proceeds very slowly; glycidonitrile forms  S-(2-cyano-2-
hydroxyethyl)-L-glutathione and  S-(1-cyano-2-hydroxyethyl)-L-
glutathione in the ratio of about 1:1.  In the enzyme-catalysed 
conjugation this ratio shifts to about 3:1 (Holechek & Kopecky, 
1981).  These authors demonstrated that no cyanide was released 
from the conjugation product of acrylonitrile with GSH, while 
cyanide was released from the conjugation product of glycidonitrile 
with GSH.  This study confirmed the findings of Boyland & Chasseaud 
(1967, 1968) concerning the participation of glutathione- S-
alkylene transferase(s) (EC in the cyanoethylation 
reaction of glutathione.  Since glutathione conjugates are 
precursors of mercapturic acids, the occurrence of mercapturic 
acids derived from acrylonitrile and glycidonitrile may be expected 
in the urine of animals exposed to acrylonitrile. 

    The major metabolite of acrylonitrile in the rat, rabbit, and 
other animals was found to be 2-cyanoethylmercapturic acid (Dahm, 
1977; Wright, 1977; Ahmed & Patel, 1979; Kopecky et al., 1979, 
1980a,b,c, 1981; Langvardt et al., 1980; Sapota & Draminski, 1981; 
Sapota & Chmielnicka, 1981; Van Bladeren et al., 1981; Ghanayem & 
Ahmed, 1982).  While 2-cyanoethylmer-capturic acid was the sole 
mercapturic acid identified in the urine of rats after iv 
administration of acrylonitrile, a second mercapturic acid of 
unestablished structure was also excreted after oral 
administration.  Langvardt et al. (1980), using 1-14C- or 2,3-14C-
acrylonitrile, found seven radioactive metabolites in rat urine.  
The 3 major metabolites included thiocyanate and 2-
cyanoethylmercapturic acid.  The third was tentatively identified 
as 4-acetyl-5-cyanotetra-hydro-1,4-2 H-thiazine-3-carboxylic acid.  
The 4 remaining metabolites represented at least one third of the 
total activity excreted; their chemical structures are not known, 
but none contained the -CN group of acrylonitrile.  Different 
results were reported by van Bladeren et al. (1981).  In common 
with Kopecky & Langvardt and colleagues, they isolated 
2-cyanoethylmercapturic acid from the urine of orally-dosed rats; 
however, 2-hydroxyethylmercapturic acid was also excreted.  It is 
suggested that this second mercapturic acid may be formed via one 
of the conjugates of glutathione with glycidonitrile,  S-(2-cyano-
2-hydroxyethyl)-L-glutathione.  The amount of mercapturic acids 
excreted relative to the dose was approximately constant up to a 
dose of acrylonitrile of 26.5 mg/kg body weight.  At higher doses, 
the amount of mercapturic acids excreted remained constant.  These 
authors and Wright (1977) suggested that this might be a 
consequence of the depletion of available glutathion at the higher 
dose levels. It seems likely that, at high exposure levels, the 
preferred metabolic pathway (conjugation of glutathione with 
acrylonitrile or its metabolite) is overloaded, and another unknown 
metabolic pathway takes over.  After an oral dose to rats of 1-14C 
acrylonitrile, 4 metabolites were found in the bile, 2 major 
metabolites being GSH conjugates of acrylonitrile (Ghanayem & 
Ahmed, 1982). 

    The report by Dahm (1977) that rats administered acrylonitrile 
excreted  S-(2-cyanoethyl)-L-cysteine has not been confirmed by any 
of the authors who have examined the glutathione conjugation 
pathway of acrylonitrile biotransformation.  Fig. 2 illustrates 
the proposed routes of mercaptide formation from acrylonitrile. 

FIGURE 2  The glucuronic acid conjugates of acrylonitrile metabolism 

    Rats treated with doses of acrylonitrile ranging from 20 to 40 
mg/kg body weight (Hoffman et al., 1976) excreted significantly 
more glucuronic acid than untreated controls or rats administered 
10 mg acrylonitrile/kg body weight.  This suggests that 
acrylonitrile-derived glucuronide might be the alternative 
substance to conjugate metabolites (van Bladereu et al., 1981).  
The results of Lambotte-Vandepaer et al. (1980) support this 
theory.  The mutagenicity of rat urine after administration of 
acrylonitrile at 30 mg/kg body weight was enhanced by treatment 
with beta-D-glucuronidase (EC prior to the Ames' 
mutagenicity assay.  This indicates that a glucuronide was cleaved 
to give a free mutagenic agent derived from acrylonitrile.  The 
dose fits the dose range that evokes a significant increase in 
glucuronic acid excretion (Hoffmann et al., 1976) and is of the 
same magnitude as that at which van Bladeren et al. (1981) 
demonstrated a depletion of glutathione in rat liver.  Quantitative aspects of acrylonitrile bio-transformation 
and elimination of its metabolites 

(a)  Effect of acrylonitrile concentration and dose

    The relationship between acrylonitrile concentrations in the 
air, cyanide and thiocyanate in the blood, and thiocyanate in the 
urine was described by Brieger et al. (1952).  At acrylonitrile 
concentrations between 55 and 220 mg/m3 (25 and 100 ppm), the blood 
and urine thiocyanate concentrations were proportional to inhaled 
acrylonitrile concentrations in rats. However, the cyanide content 
of blood was measurable only at the highest acrylonitrile 
concentration.  In dogs, cyanide could be detected in blood at an 
acrylonitrile concentration of 110 mg/m3 and cyanide concentrations 
in blood were proportional to the inhaled acrylonitrile 
concentrations in the range of 110-220 mg/m3 (50 - 100 ppm).  Data 
indicate that a certain acrylonitrile concentration must be exceeded 
to provide conditions for the formation of enough cyanide to surpass 
the metabolic capacity of rhodanese or the supply of co-factors; 
this concentration is lower in the dog than in the rat. 

    In mice and rats, the dose of acrylonitrile was directly 
related to the cyanide levels in blood, liver, kidney, and brain 
(Ahmed & Patel, 1981), and, in rats, the ip administration of 
acrylonitrile at 20-60 mg/kg body weight or oral administration at 
15-60 mg/kg body weight also produced a proportional increase in 
thiocyanate excretion in the urine. 

    However, thiocyanate is always present in urine (9 mg/litre in 
rats) (Brieger et al., 1952), and the acrylonitrile exposures 
required to exceed this level significantly are high.  Thus, urine 
thiocyanate levels would not give an accurate estimate of exposure 
at the atmospheric acrylonitrile concentrations found in industry, 
at present. 

    The observation of Hoffmann et al. (1976) suggested a possible 
alternative conjugating route for metabolites at higher 
acrylonitrile exposure levels involving glucuronic acid.  Before 
this is confirmed, the effects on carbohydrate metabolism and 
glucose utilization in rats must be considered, as well as the 
possibility that this alternative pathway of glucose metabolism 
leading to the formation of glucuronic acid, and thus elevated 
glucuronic acid levels in urine, may be stimulated by acrylonitrile.  
From the standpoint of a possible exposure test, however, it is 
emphasized that high doses of acrylonitrile are required to 
increase excretion of glucuronic acid in urine, but such doses 
would only occur in cases of accidental overexposure. 

(b)  Differences between species

    The work of Brieger et al. (1952) revealed that, at the same 
acrylonitrile exposure concentrations, cyanide blood levels in dogs 
were far higher than in rats.  This was apparently due to a less 
efficient detoxification of cyanide to thiocyanate in dogs since, 
when exposed to an acrylonitrile concentration of 217 mg/m3 (100 
ppm), the total sum of cyanide and thiocyanate concentrations in 
blood was about 260 mol/litre in dogs and 840 mol/litre in rats.  
Although the normal thiocyanate blood level was about 150 
mol/litre in the rat and only about 55 mol/litre in the dog, the 
elevation caused by acrylonitrile was far higher in rats, 
suggesting that rats metabolize acrylonitrile to cyanide at a 
substantially higher rate and are able to detoxify it more 
efficiently than dogs. 

    Mice excrete more thiocyanate than rats, at a given dose of 
acrylonitrile, even though detoxification of cyanide to thiocyanate 
in mice is apparently less efficient than in rats. Co-administration
of acrylonitrile and thiosulfate resulted in a 3-fold increase in 
thiocyanate excretion in mice, while in rats the effect was much 
smaller (Gut et al. 1975; Silver et al., 1982).  Moreover, the 
thiosulfate significantly reduced mortality in mice, but the 
reduction in rat mortality was only slight, confirming that 
enhanced detoxification of cyanide in mice is important. 

    Ahmed & Patel (1981) also observed that the rate of metabolism 
of acrylonitrile was higher in mice than in rats. 

(c)  Time course of elimination of acrylonitrile metabolites

    The excretion in urine of 14C-acrylonitrile-derived mercapturic 
acids follows shortly after ip, sc, iv, or oral administration of 
14C-acrylonitrile in rats (Gut et al., 1981a) and rapidly 
decreases, whereas the excretion of thiocyanate from acrylonitrile 
given orally or intra-peritoneally increases after a time lag 
culminating between hours 8 and 12 in rats, but sooner in mice and 
Chinese hamsters (Gut et al., 1975).  The time course of 
acrylonitrile-derived mercapturic acid excretion in rats was 
closely correlated with free acrylonitrile concentrations in blood 
and liver (Nerudova et al., 1980a; Gut et al., 1981a), while that 
of thiocyanate was not, whatever the route of administration. 

(d)  Effect of the route of administration

    The excretion of thiocyanate by rats, mice, and Chinese 
hamsters after oral, ip, sc, and iv administration of 14C-
acrylonitrile represented 20-40%, 5%, 5%, and 1%, respectively, of 
the dose administered.  However, urinary excretion of radioactivity 
was almost quantitative (Gut et al., 1981a); subtracting the 
thiocyanate excretion from total urinary metabolites (radioactivity) 
revealed that excretion of acrylonitrile-mercapturic acids (and 
other possible acrylonitrile metabolites) is independent of the 
route of administration (Kopecky et al., 1980a).  When 1-14C-
acrylonitrile was administered orally to rats, 27% of the dose had 
been excreted in the bile in 6 h, mainly in the form of 2 
glutathione conjugates of acrylonitrile (Ghanayem & Ahmed, 1982). 

(e)  Metabolic interactions of acrylonitrile with other xenobiotics

    Oral administration of an equimolar dose of acrylonitrile (0.5 
mmol/kg body weight) to rats did not influence the elimination of 
phenol from benzene.  However, benzene, toluene, ethylbenzene, or 
styrene (0.5 mmol/kg body weight) markedly decreased the rate and 
total excretion of thiocyanate from an equal dose of acrylonitrile 
given orally; higher doses of the solvents caused greater 
inhibition (Gut et al., 1981). On the other hand, subcutaneous 
administration of benzene and styrene increased the excretion of an 
equal dose of 14C-acrylonitrile (0.5 mmol/kg body weight) during 
the first 4 h and decreased it between the 8th and l2th hours 
(owing to inhibited thiocyanate formation and excretion).  The 
total of metabolites excreted was unaffected.  The co-administration
of industrial solvents markedly increased the lethality of 
acrylonitrile (Gut et al., 1981a).  Inhibition of the oxidative 
metabolism of acrylonitrile in rats by a cytochrome P-450 inhibitor 
(1-phenylimidazole) inhibited completely the excretion of  N-
acetyl- S-(2-hydroxyethyl) L-cysteine in favour of the excretion of 
 N-acetyl- S-(2-cyanoethyl)-L-cysteine (van Bladeren et al., 1981).  
The latter compound, the authors considered, resulted from direct 
cyanoethylation of glutathione, whereas the former was formed via 
the epoxide, glycidonitrile.  Overnight fasting and cobaltous 
chloride pre-treatment increased the biliary excretion of 
metabolites, while phenobarbital did not induce any change, and 
dimethyl maleate significantly decreased the excretion (Ghanayem & 
Ahmed, 1982). 


    Studies, particularly animal studies, on the absorption, 
distribution, biotransformation, and elimination of acrylonitrile 
have shown that a small fraction of the acrylonitrile absorbed is 
rapidly eliminated in the urine without biotransformation, while 
the remainder is biotransformed via several pathways, a number of 
metabolites being excreted in urine; some of these metabolites are 
unique to acrylonitrile. 

    The absorption studies have also clearly shown that, in 
addition to uptake of acrylonitrile by inhalation, skin penetration 
can be an important route of entry, particularly in the presence of 
liquid acrylonitrile.  Thus, in human studies, unless performed 
under controlled conditions, a good correlation cannot necessarily 
be expected between a bioindicator of uptake and ambient air 
measurements of acrylonitrile, even when carried out with personal 

    Possible indicators of acrylonitrile uptake at present include:  
acrylonitrile in urine, acrylonitrile-derived mercapturic acids in 
urine, total thioethers in urine, and thiocyanates in urine. 

    Houthuijs et al. (1982) studied the excretion pattern of 
acrylonitrile in the urine of 15 exposed workers over a 7-day 
period, with a control group of 41 unexposed workers.  They noted 
that the concentrations of acrylonitrile in urine peaked at the 
end, or shortly after the end, of the working day, decreasing 
rapidly until the beginning of the next working day without, 
however, falling to the levels in the control group. Correlations 
have been found between acrylonitrile concentrations in air and 
those in urine.  In the control group, a significant increase in 
the acrylonitrile excretion in urine was found with the number of 
cigarettes smoked.  For a mean acrylonitrile concentration in air 
of 0.28 mg/m3 (0.13 ppm), the mean acrylonitrile level in urine at 
the end of the working day was 38 g/litre, using the headspace 
chromatographic technique.  In the control group for non-smokers, 
the mean level of acrylonitrile in urine was 2 g/litre and for 
smokers (20-30 cigarettes per day) 9.0 g/litre. 

    Sakurai et al. (1978) have also established a relationship 
between acrylonitrile concentrations in air and levels in urine for 
a group of 102 exposed workers and compared them with 62 controls.  
For an air concentration of 0.2 mg/m3 (0.1 ppm) (as measured by 
personal samplers), an acrylonitrile level in urine of 3.0 g/litre 
was found, using the Sato et al. (1975) method of analysis 
(separation by azeotropic distillation and determination by gas 
chromatography).  The urine samples were collected at the end of 
the working day. At an air concentration of 1.1 mg/m3 (0.5 ppm), 
the level of acrylonitrile in urine was 19.7 g/litre, and at a 
concentration in air of 9 mg/m3 (4.2 ppm) the corresponding level 
in urine was 359.6 g/litre.  Acrylonitrile could not be detected 
in the urine of controls.  At the same time, an increase in the 
thiocyanate level in urine was noted, particularly at the higher 
exposure levels. 

    According to Houthuijs et al. (1982), the differences found 
between the urine levels of acrylonitrile in the two studies are 
most likely due to differences in analytical techniques. 

    The validity of the determination of urine levels of 
acrylonitrile using gas chromatography-head space analysis for 
monitoring acrylonitrile-exposed workers was established by Benchev 
et al. (1982). 

    A promising method for estimating total acrylonitrile uptake 
seems to be the determination of acrylonitrile-derived mercapturic 
acids; such acids are specific for acrylonitrile and are absent 
from normal urine.  They have been shown in experimental animal 
studies to be well correlated with the free acrylonitrile 
concentration in blood (Nerudova et al., 1980; Gut et al., 
1981a,b); animal data also indicate that the capacity of the enzyme 
systems to produce the acrylonitrile-derived mercapturic acids is 
unlikely to be exceeded at the exposure levels of interest (van 
Bladeren et al., 1981).  Draminski & Trojanowska (1983) established 
the presence of  S-(2-cyanoethyl) mercapturic acid in the urine of 
13 workers exposed to acrylonitrile, using a gas chromatographic 
technique.  The concentrations ranged between 50 and 200 mg/litre 
for ambient acrylonitrile levels between 3.3 and 9.8 mg/m3 (1.5 and 
4.5 ppm).  The "total thioethers" were also determined in the urine 
samples by a spectrophotometric method (Kopecky, 1982) and shown to 
be strongly correlated with the  S-(2-cyanoethyl) mercapturic acid 
excretion, indicating that, in the case of exposure to pure 
acrylonitrile, the major part of the sum of "thioethers" is 
represented by this specific mercapturic acid. 

    Increased glucuronic acid excretion was reported by Ostrovskaja 
et al. (1976) in 45.5% of workers exposed to acrylonitrile 
concentrations of 0.7-1.5 mg/m3 (0.3-0.7 ppm). 

    The recent studies reported above show that biological 
monitoring may become a suitable approach for assessing 
acrylonitrile uptake, in particular in relation to the working 
environment.  Both acrylonitrile in urine and acrylonitrile-derived 
mercapturic acids in urine seem to be the most suitable 
bioindicators of uptake, at present, as they have the advantage of 
specificity.  More work is needed to resolve the apparent 
discrepancies due to analytical techniques and to determine the 
half-lives.  This should make it possible to establish the most 
appropriate sampling time with respect to exposure and help in the 
determination of the concentrations of concern. 

    Interest in the determination of total "thioethers" in urine as 
a bioindicator of uptake lies in the greater simplicity of the 
analytical techniques used.  However, more work is needed, 
particularly with regard to interferences and half-lives. 

    The possibility of estimating acrylonitrile exposure in smokers 
was suggested by Della Fiorentina & De Wiest (1979), who observed 
that determination of carboxyhaemoglobin in blood makes it possible 
to calculate the amount of thiocyanate present in urine that is due 
to smoking, and thus to calculate the uptake of acrylonitrile.  
However, experience shows that there can be marked variations in 
thiocyanate levels in smokers, which greatly exceed those in non-
smokers occupationally-exposed to acrylonitrile (Czajkowska et al., 


7.1.  Acute Toxicity

7.1.1.  Lethal doses and concentrations  Lethal doses

    The range of acute LD50 values for acrylonitrile in different 
laboratory mammals is generally between 25 and 186 mg/kg body 
weight (Table 9), though a value of 282 mg/kg body weight was 
observed when liquid acrylonitrile was applied to the skin of the 
tail of male rats (Zotova, 1976).  Mice are more sensitive than 
rats, guinea-pigs, and rabbits.  There seems to be little 
consistency in the effects of route or vehicle of administration, 
or of sex, on the LD50 level.  The LD50 for dogs was not reported, 
but they tolerated iv administration of acrylonitrile at 50 mg/kg 
body weight and died after 300 mg/kg (Graham, 1965).  The LD50 
values reported are an order of magnitude higher than the LD50 for 
cyanide (one of the metabolites of acrylonitrile), but markedly 
lower than those for industrial solvents and monomers of plastics 
(the LD50 for benzene and its derivatives being about 2000-3000 
mg/kg body weight).  Lethal concentrations in the air

    The range of acute LC50 s for 4-h inhalation of acrylonitrile is 
between 150 and 1250 mg/m3 (Table 10).  Dogs appeared to be the 
most sensitive of the species tested and the sensitivity decreased 
in the following order: mice, rabbits, cats, rats, guinea-pigs, the 
latter being apparently the most resistant to inhalation exposure.  
The exposure of 315-350 cm2 of the skin of rabbits to an 
acrylonitrile concentration of 44-62 g/m3, in an exposure chamber, 
such that the animals were breathing pure air, proved fatal after 
2.5-4 h.  Inhalation exposure to 0.58-0.67 g/m3 was fatal for 3 
rabbits within 2-3 h (Rogaczewska, 1975). 

    In the 3 species of insects tested in a fumigation chamber
for 8 h, the LC50 value was found to be 700-1900 mg/m3 (Bond &
Buckland, 1976).  Lindgren et al. (1954) exposed 8 insect
species for 2 or 6 h and found LC50 values of 1000-4500 mg/m3 .

Table 9.  Acute LD50 values for acrylonitrile: effect of animal species
strain and route of administration
Species/strain/sex         Number      Route    LD50 (mg/kg    Vehicle     Reference
                                                body weight)
mouse/-/male               M + F 333   oral     36             water       Tullar (1947)
mouse/-/female             M + F 333   oral     48             water       Tullar (1947)
mouse/-/M + F              169         oral     40             olive oil   Tullar (1947)
mouse/H strain/-           -           oral     25             physiol.    Benesh & Cherna 
                                                               saline      (1959)
mouse/-/-                  -           oral     40-46          -           American Cyanamid 
mouse/-/female             M + F 325   ip       48             water       Tullar (1947)
mouse/-/male               M + F 325   ip       40             water       Tullar (1947)
mouse/NMRI or "SPF"/-      -           ip       50             -           Zeller et al. 
mouse/ICR/female           -           ip       47             -           Yoshikawa (1968)
mouse/H strain/-           -           sc       35("technical  physiol.    Benesh & Cherna 
                                                AN")          saline      (1959)
mouse/"inbred"/male        60          sc       50 (2 h)      physiol.    Graham (1965)
                                                25 (24 h)
mouse/BN/male              60          sc       34             -           Knobloch et al. 
rat/Sherman/-              groups of   oral     93             -           Smyth & Carpenter 
                           6-10                                            (1948)
rat/Wistar/-               -           oral     101            -           Paulet & Vidal 
rat/Wistar or Stock/-      -           oral     128            -           Zellar et al.     
rat/Wistar-Stamm/male      -           oral     82             -           von Borchardt 
                                                                           et al. (1970)  
rat/Wistar-Stamm/female    -           oral     86             -           von Borchardt 
                                                                           et al. (1970)
rat/-/M + F                80          oral     84             water       Tullar (1947)
rat/-/M + F                51          oral     72             olive oil   Tullar (1947)
rat/Wistar/-               -           oral     78             physiol.    Benesh & Cherna 
                                                               saline      (1959)
rat/Sprague-Dawley/male    20          oral     186            water       Monsanto (1975)
rat/Sprague-Dawley/female  20          oral     186            water       Monsanto (1975)

Table 9.  (contd.)
Species/strain/sex         Number      Route    LD50 (mg/kg    Vehicle     Reference
                                                body weight)

rat/Wistar/male            110         ip       100            -           Knobloch et al. 
rat/Wistar/-               -           ip       65             poly-       Paulet & Vidal 
                                                               ethylene    (1975)
rat/Wistar/male            110         sc       80             -           Knobloch et al. 
rat/"albino"/male          -           sc       96             water       Magos (1962)
rat/"white"/male           -           skin of  282            liquid      Zotova (1976)
                                       tail                    acrylonitrile
rat/"white"/male           -           skin of  148            liquid      Zotova (1976)
                                       abdomen                 acrylonitrile
guinea-pig/-/-             -           oral     50             -           Carpenter et al. 
guinea-pig/-/-             -           oral     85             olive oil   Tullar (1947)
guinea-pig/-/M & F         30          oral     56             -           Jedlicka et al. 
guinea-pig/-/-             -           sc       130            -           Ghiringhelli (1954)
guinea-pig/-/-             11          iv       72             water       Tullar (1947)
guinea-pig/Hartley-/male   12 or more  intact   0.46 ml/kg     -           Roudabush et al. 
                                       skin                                (1965)
                                       abraded  0.86 ml/kg     -           Roudabush et al. 
                                       skin                                (1965)
guinea-pig/-/-             -           skin     0.25 ml/kg     -           Smyth & Carpenter 
rabbit/-/-                 -           oral     93             -           Lefaux (1966)
rabbit/-/-                 -           iv       69             -           Paulet & Desnos 
rabbit/"white"/M & F       12 or more  abraded  0.28 ml/kg     -           Roudabush et al. 
                                       skin                                (1965)

Table 10.  Acute lethal effect of single inhalation of acrylonitrile: effect of
duration and concentration of acrylonitrile
Species/strain/sex     Number   Concentration  Duration  Mortality  Reference
                                (mg/m3)       (h)      (died/
white mouse/stock/-    6        600            0.5       0/6        McOmie (1949)
                       6        1500           0.5       5/6        McOmie (1949)
                       6        5800           0.5       5/6        McOmie (1949)
                       6        900            1         1/6        McOmie (1949)
                       6        900            2         3/6        McOmie (1949)
                       6        1700           1         6/6        McOmie (1949)

mouse/BN/male          12       300            4         LC50       Knobloch et al. (1971)

rat/Sherman/-          6        1085           4         0/6        Smyth & Carpenter et al. (1971)
                       6        2170           4         6/6        Smyth & Carpenter et al. (1971)

rat/Sherman/female     6        1085           4         2/6 to     Carpenter et al. (1949)

rat/Wistar/-           20       54             7         0/20       Brieger et al. (1952)
                       20       109            7         0/20       Brieger et al. (1952)
                       20       163            7         0/20       Brieger et al. (1952)
                       20       217            7         4/20       Brieger et al. (1952)

rat/Wistar/male        12       470            4         LC50       Knobloch et al. (1971)

rat/Osborne-Mendel/-   16       2750           1         0/16       Dudley & Neal (1942)
                       16       3230           1         4/16       Dudley & Neal (1942)
                       16       5300           1         13/16      Dudley & Neal (1942)
                       16       660            2         0/16       Dudley & Neal (1942)
                       16       1290           2         6/16       Dudley & Neal (1942)
                       16       2730           2         16/16      Dudley & Neal (1942)
                       16       280            4         0/16       Dudley & Neal (1942)
                       16       680            4         5/16       Dudley & Neal (1942)
                       16       1380           4         16/16      Dudley & Neal (1942)
                       16       290            8         0/16       Dudley & Neal (1942)
                       16       460            8         1/16       Dudley & Neal (1942)
                       16       590            8         7/16       Dudley & Neal (1942)
                       16       690            8         15/16      Dudley & Neal (1942)

Table 10. (contd.)
Species/strain/sex     Number   Concentration  Duration  Mortality  Reference
                                (mg/m3)       (h)      (died/
rat/Wistar/male        3        650            3         1/3        Appel et al. (1981)
                       3        1100           2         3/3        Appel et al. (1981)
                       3        2600           0.5       1/3        Appel et al. (1981)
                       6        3000           0.5       6/6        Appel et al. (1981)

guinea-pig/-/-         8        580            4         0/8        Dudley & Neal (1942)
                       8        1250           4         5/8        Dudley & Neal (1942)
                       8        2520           4         8/8        Dudley & Neal (1942)

guinea-pig/-/-         12       990            4         LC50       Knobloch et al. (1971)

rabbit/"albino"/-      2        290            4         0/2        Dudley & Neal (1942)
                       2        560            4         2/2        Dudley & Neal (1942)
                       2        1260           4         2/2        Dudley & Neal (1942)
rabbit/-/-             5        670 - 1100     2-3       5/5        Rogaczewska (1975)

cat/-/-                4        210            4         0/4        Dudley & Neal (1942)
                       2        600            4         0/2        Dudley & Neal (1942)
                       2        1300           4         2/2        Dudley & Neal (1942)

dog/-/-                3        63             4         0/3        Dudley & Neal (1942)
                       2        140            4         1/2        Dudley & Neal (1942)
                       3        213            4         0/3        Dudley & Neal (1942)
                       2        240            4         2/2        Dudley & Neal (1942)

dog/-/-                4        108            7         0/4        Brieger et al. (1952)
                       4        163            7         0/4        Brieger et al. (1952)
                       6        213            7         6/6        Brieger et al. (1952)

Rhesus monkey/-/-      3        163            7         1/3        Brieger et al. (1952)
---------------------------------------------------------------------------------------------------  Lethal concentrations in water

(a)  Fish

    Acute toxicity, determined by a static bioassay at 25 C, 
revealed TLm (median tolerance limit, i.e., a concentration of 
acrylonitrile killing 50% of the test organisms within a specified 
time) values ranging from 25.5 to 44.6 mg/litre at 24 h, and from 
11.8 to 33.5 mg/litre at 96 h.  There were no apparent significant 
differences in the sensitivity of various kinds of fish (Table 11). 

(b)  Invertebrates

    For the brown shrimp  (Crangon crangon), the LC50 for a 24-h 
exposure was 10-33 mg/litre (Portman & Wilson, 1971). Bandt (1953) 
exposed several species of arthropods (a shrimp-like crustaceae and 
3 types of larvae) to 20-100 mg acrylonitrile/litre water and found 
marked species and individual differences: a lethal effect was 
observed in some species with 25 mg/litre after 48 h, while other 
species were not affected after 3 days.  The most resistant species 
were unaffected by 100 mg/litre after 24-48 h.  The results of 
studies by Rajendran & Muthu (1981) showed that acrylonitrile 
affects the activity of the phosphorylase and acetylcholinesterase 
enzymes in  Tribolium castaneum Herbst, and  Trogoderma granarium 

7.1.2.  Clinical observations

    The inhalation studies of Dudley & Neal (1942), Brieger et al. 
(1952), and Rogaczewska (1975), and the results of oral and 
parenteral administration (Ghiringhelli, 1954; Benesh & Cherna, 
1959; Paulet & Despos, 1961; Graham, 1965; Paulet et al., 1966) 
indicate that animals inhaling lethal concentrations of 
acrylonitrile, or administered lethal dosages of acrylonitrile 
orally or parenterally, showed rather similar effects: excitability 
and stimulated breathing, shallow rapid breathing, slow gasping 
breathing, apnoea, convulsions, and death.  Vomiting occurred in 
cats, dogs, and monkeys after inhaling acrylonitrile, and in rats 
following parenteral administration.  Reddening of the skin of the 
ears, nose, and feet (in rhesus monkeys, also of the face and 
genital organs) and mucosa was accompanied by lachrymation, nasal 
discharge, and salivation, not only after inhalation exposure, but 
also following oral and sc administration, while hind-leg 
incoordination, paresis or paralysis, were observed in rats after 
oral administration, and in rabbits after iv administration. 

Table 11.  Median tolerance limit values (TLm)a for various fish exposed to 
Species                Water type         TLm (mg/litre)    Reference
                                       24 h    48 h   96 h
Fathead minnow         hard            32.7    16.7   14.3   Henderson et al. (1961)
 (Pimphales promelas)   soft            34.3    21.5   18.1   Henderson et al. (1961)

Minnow  (Phoxinus       -               38.2    17.6   -      Marcoci & Ionescu (1974)

Bluegill  (Lepomis      soft            25.5    14.3   11.8   Henderson et al. (1961)

Guppy  (Lebistes        soft            44.6    33.5   33.5   Henderson et al. (1961)

Goldfish  (Carassius    -               -       -      40     Paulet & Vidal (1975)

Carp  (Cyprinus         -               37.4    24.0   -      Marcoci & Ionescu (1974)

Rainbow trout          hard            -       70     -      Jackson & Brown (1970)
 (Salmo gairdneri) 

Pin perch              sea             24.5    -      -      Daugherty & Garett (1951)
(marine fish)         (30/l tank)
 (Lagodon rhomboides) 

Rainbow trout          tap,            -       5b     -      Sloof (1979)
 (Salmo gairdneri)     dechlorinated,
                       3.6 mg/litre

                       hard            15      -      -      Sloof (1979)

Zebra fish             same            (LC50)
a   TLm median tolerance limit, a concentration of acrylonitrile killing
    50% of the test organisms within a specified time.
b   Minimal concentration changing respiratory frequency.

(a)  Effects on the skin

    Direct application of liquid acrylonitrile to the shaved skin 
of rabbits induced slight local vasodilation immediately, without 
any systemic effect (1-2 ml covering 100-200 cm2) or with an 
increased respiratory rate (3 ml over 300 cm2) (McOmie, 1949).  
Tuller (1947) observed erythema in only one of 3 areas of abraded 
skin, following application of 1 ml of acrylonitrile on a gauze pad 
covered by rubber sheeting. However, Zeller et al. (1969) found 
that a 15-min application of acrylonitrile on a cotton pad to 
shaved skin resulted in skin oedema, and a 20-h application, in 

slight necrosis. Guinea-pigs appear to be more sensitive than 
rabbits; the application of a 2% solution of acrylonitrile in 
acetone for 24 h, under occlusion,