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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, 1985

         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
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    toxicology. Other activities carried out by the IPCS include the
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    coordination of laboratory testing and epidemiological studies, and
    promotion of research on the mechanisms of the biological action of

        ISBN 92 4 154189 X    

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    1.1. Summary
         1.1.1. Properties, uses, and analytical methods
         1.1.2. Environmental sources and environmental
                transport and distribution
         1.1.3. Environmental levels and exposures
         1.1.4. Metabolism of acrylamide
         1.1.5. Effects on man and animals
         1.1.6. Mutagenicity and carcinogenicity
         1.1.7. Teratogenicity and reproduction
         1.1.8. Dose-effect and dose-response relationships
         1.1.9. Evaluation of health risks for man
    1.2. Recommendations for further research
         1.2.1. Analysis
         1.2.2. Exposure
         1.2.3. Metabolism and indicators of exposure
         1.2.4. Effects


    2.1. Identity
    2.2. Chemical and physical properties
    2.3. Sampling and analytical methods


    3.1. Production levels, processes, and uses
         3.1.1. World production
         3.1.2. Production processes
         3.1.3. Uses
    3.2. Release into the environment
    3.3. Disposal of wastes


    4.1. Transport in the environment
    4.2. Biomagnification and bioconcentration
    4.3. Transformation


    5.1. Environmental levels
         5.1.1. Ambient air and soil
         5.1.2. Water
         5.1.3. Food
    5.2. General population exposure
    5.3. Occupational exposure


    6.1. Experimental animal studies
         6.1.1. Absorption and distribution
         6.1.2. Metabolism
         6.1.3. Elimination and excretion
    6.2. Human studies


    7.1. Neurological effects
         7.1.1. Neurobehavioural effects
         7.1.2. Electrophysiological effects
        Peripheral effects
        Central nervous system effects
         7.1.3. Morphological effects
         7.1.4. Biochemical effects
        Effects on axonal transport
        Effects on energy production
                         and neuronal metabolism
        Effects on CNS neurochemistry
    7.2.  In vitro toxicity studies
    7.3. Effects on other organs
    7.4. Genotoxic effects and carcinogenicity studies
         7.4.1. Mutagenicity and other related short-term tests
         7.4.2. Carcinogenicity studies
    7.5. Teratogenicity and reproductive studies
    7.6. Factors modifying effects
         7.6.1. Chemical modification of acrylamide toxicity
         7.6.2. Age
         7.6.3. Sex differences
         7.6.4. Species
    7.7. Dose-response and dose-effect relationships
         7.7.1. Dose-response relationships
         7.7.2. Dose-effect relationships
        Manifestations of neuropathy
        Electrophysiological effects
        Morphological effects
        Effects on axonal transport
        Neurobehavioural effects


    8.1. Clinical studies and case reports
    8.2. Epidemiological studies
    8.3. Dose-effect and dose-response relationships


    9.1. Aquatic organisms
         9.1.1. Invertebrates
         9.1.2. Fish and amphibia
    9.2. Terrestrial plants
    9.3. Microorganisms



    11.1. General considerations
    11.2. Assessment of exposure
    11.3. Assessment of adverse effects
    11.4. Exposure of the environment
    11.5. Occupational exposure




Dr N. Aldridge, Medical Research Council, Carshalton, Surrey,
   United Kingdom  (Chairman)

Dr M. Berlin, Monitoring and Assessment Research Centre,
   University of London, London, United Kingdom

Prof J. Cavanagh, Institute of Neurology, London, United

Dr K. Hashimoto, Department of Hygiene, School of Medicine,
   Kanazawa University, Ishikawa, Japan  (Vice-Chairman)

Dr D.G. Hatton, US Food and Drug Administration, Department of
   Health and Human Services  (Rapporteur)

Prof M. Ikeda, Department of Environmental Health, Tohoku
   University School of Medicine, Sendai, Japan

Dr P. Le Quesne, National Hospital for Nervous Diseases,
   London, United Kingdom

Prof A. Massoud, Ain Shams University, Cairo, Egypt

Dr P.K. Ray, Industrial Toxicology Research Centre, Lucknow,

Prof I.V. Sanotsky, Research Institute of Industrial Hygiene
   and Occupational Diseases, USSR Academy of Medical
   Sciences, Moscow, USSR

Dr H.A. Tilson, Laboratory of Behavioral and Neurological
   Toxicology, NIEHS, Research Triangle Park, North Carolina,

 Representatives from Other Organizations

Mr S. Batt, Monitoring and Assessment Research Centre,
   University of London, London, United Kingdom

Dr L. Shukar, Monitoring and Assessment Research Centre,
   University of London, London, United Kingdom

Mr J.D. Wilbourn, International Agency for Research on Cancer,
   Unit of Carcinogen Identification and Evaluation, Lyons,

 WHO Secretariat

Dr M. Draper, International Programme on Chemical Safety,
   World Health Organization, Geneva, Switzerland

Dr E.M.B. Smith, International Programme on Chemical Safety,
   World Health Organization, Geneva, Switzerland  (Secretary)

Ms A. Sunden, International Register of Potentiallly Toxic
   Chemicals, Geneva, Switzerland


    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 -


    Following the recommendations of the United Nations 
Conference on the Human Environment held in Stockholm in 1972, 
and in response to a number of World Health Assembly resolutions 
(WHA23.60, WHA24.47, WHA25.58, WHA26.68), and the recommendation 
of the Governing Council of the United Nations Environment 
Programme, (UNEP/GC/10, 3 July 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 

    A WHO Task Group on Environmental Health Criteria for 
Acrylamide was held at the British Industries Biological Research 
Association (BIBRA), Carshalton, Surrey, United Kingdom, from 
3-5 December, 1984.  Dr E.M.B. Smith opened the meeting on behalf 
of the Director-General.  The Task Group reviewed and revised the 
draft criteria document and made an evaluation of the health risks 
of exposure to acrylamide. 

    The initial draft was prepared by DR M. BERLIN with the 
assistance of DR L. SHUKAR and MR S. BATT of the MONITORING AND 

    The efforts of all who helped in the preparation and 
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.  The UK Department of Health 
and Social Security generously supported the cost of printing. 


1.1.  Summary

1.1.1.  Properties, uses, and analytical methods

    Acrylamide is a white crystalline solid produced from 
acrylonitrile, which is present as a residue in technical grades 
of acrylamide at concentrations ranging from 1 to 100 mg/kg.  
Acrylamide readily undergoes polymerization, resulting in a 
highly cross-linked insoluble gel of polyacrylamide.  Commercial 
polyacrylamide contains 0.05 - 5.0% acrylamide.  Hydroquinone 
monomethylether, t-butylpyrocatechol,  N-phenyl-2-naphthylamine, 
and copper (ion) may be used as stabilizers. 

    Acrylamide is mainly used in the production of polymers and 
copolymers for various purposes.  Polyacrylamides are useful as 
flocculents in the treatment of waste water and the purification 
of drinking-water.  Acrylamide is also used as a grouting agent 
and in the construction of dam foundations and tunnels. 

    Methods for the determination of acrylamide in polymers, air, 
water, and biological materials have been devised using gas 
chromatography, high-performance liquid chromatography, and 
differential pulse polarography.  No method has so far been 
described for the determination of either acrylamide bound to 
blood and tissue proteins or its metabolites in the urine. 

    The reported sensitivity for the determination of acrylamide 
in air, using gas chromatography, is 5 g/m3 and, using electron 
capture and flame ionization detection, 30 g/m3.  Sampling of 
acrylamide (vapour and dust) in air is performed using midget 
impingers.  Determination of acrylamide in polyacrylamide can be 
accomplished, with a sensitivity of less than 1 mg/kg, using 
differential pulse polarography.  The detection limit for 
acrylamide in water is 0.1 g/litre, using electron capture gas 
chromatography after derivatization, though the recovery of 
acrylamide is rather poor.  Derivatization followed by high-
performance liquid chromatography is less sensitive (0.2 g/litre), 
but is more suitable for the routine analysis of both natural and 
polluted water.  Free acrylamide in biological samples such as 
plasma and tissue homogenates can be determined, by electron 
capture-gas chromatography, with a detection limit of 10 

1.1.2.  Environmental sources and environmental transport and 

    All acrylamide in the environment is man-made, the main 
source being the release of the monomer residues from 
polyacrylamide used in water treatment or in industry.  The most 
important environmental contamination results from the use of 
acrylamide in soil grouting, because of contamination of ground 
water.  Chemical decontamination of acrylamide-containing liquid 
wastes and solids is possible, but the costs, in most instances, 
are high. 

    Because it is highly soluble in water, acrylamide is 
extremely mobile in the aqueous environment and is readily 
leachable in soil.  It is unlikely to enter and be transported in 
the atmosphere to any significant extent, because of its low 
vapour pressure.  Biodegradation is likely to occur. 

    A wide variety of microbes possess the ability to degrade 
acrylamide.  However, there is a latent period of several days 
before there is any significant degradation.  The residence 
period for acrylamide may be of the order of days, weeks, or 
months, in rivers and coastal areas of low microbial activity.  
The half-life in aerobic soil, which is of the order of several 
days at 20 C, increases with decreasing temperature. 

    Acrylamide is unlikely to be removed during sewage treatment 
and has been shown to pass through waterworks mainly unchanged. 

1.1.3.  Environmental levels and exposures

    Because polyacrylamide is used in water treatment, residues 
of acrylamide may be found in potable water.  In most countries, 
such residues are limited to 0.25 g/litre by maintaining the 
concentration of acrylamide monomer in the polyacrylamide used 
for water treatment at 0.05%.  Concentrations of acrylamide in 
effluents from polyacrylamide-using factories generally range 
from less than 1 to 50 g/litre.  However, 1.5 mg 
acrylamide/litre has been measured downstream from industrial 
effluent discharges.  Levels reported in receiving streams and 
rivers are variable and dependent on the extent of dilution.  A 
level of 0.3 g/litre was detected at a waterworks intake 
downstream from an effluent discharge from a clay pit.  In the 
vicinity of local grouting operations, high levels of acrylamide 
may be found in wells and ground water; a concentration of 400 
mg/litre was reported in one such well. 

    Monitoring of acrylamide concentrations in air and soil close 
to 6 acrylamide-producing plants in the USA failed to demonstrate 
any acrylamide in the air (detection limit 0.1 g/m3) or in the 
soil (detection limit 0.02 mg/kg). 

    Polyacrylamides are also used in the washing and packaging of 
prepacked foods and vegetables.  The US Food and Drug 
Administration has limited the amount of monomer in 
polyacrylamide for use in paper or cardboard in contact with food 
to 0.2% (2 g/kg).  In the Federal Republic of Germany, the level 
of polyacrylamide used in foodstuff packaging is limited to 0.3% 
(3 g/kg) and the level of residual acrylamide monomer to 0.2% 
(2 g/kg)a. 

a   Bundesministerium fr Jugend, Familie und Gesundheit,
    personal communication, 1984.

    Occupational exposure to acrylamide occurs mainly through 
skin absorption and inhalation in acrylamide-producing plants.  
Personal sampling in such plants has shown average levels in 
workplace air of about 0.6 mg/m3, with a range of 0.1 - 3.6 mg/m3 
in heavily-exposed areas.  Measurements resulting from stationary 
sampling were generally 2 - 3 times lower.  This indicates the 
importance of taking work procedures into account in the 
assessment of exposure.  Published figures from the USA indicate 
that about 20 000 workers may be exposed to acrylamide.  Although 
exposure levels have not been reported for grouters, the 
potential for hazard from this use is probably greater than from 
other uses, because of the uncontrolled nature of the exposure. 

1.1.4.  Metabolism of acrylamide

    Acrylamide is readily absorbed by ingestion, inhalation, and 
through the skin.  Absorbed acrylamide is distributed in body 
water compartments and passes through the placental barrier.  In 
rats, biotransformation of acrylamide occurs through glutathione 
conjugation and through decarboxylation.  At least 4 urinary 
metabolites have been found in rat urine, of which mercapturic 
acid and cysteine- S-propionamide have been identified.  
Acrylamide and its metabolites are accumulated (protein-bound) in 
both nervous system tissue and blood (bound to haemoglobin).  
Accumulation in the liver and kidney as well as the male 
reproductive system has also been demonstrated.  The results of 
animal studies indicate that acrylamide is largely excreted as 
metabolites in urine and bile.  Because of the enterohepatic 
circulation of biliary metabolites, faecal excretion is minimal.  
Two-thirds of the absorbed dose is excreted with a half-life of a 
few hours.  However, protein-bound acrylamide or acrylamide 
metabolites in the blood, and possibly in the central nervous 
system, have a half-life of about 10 days.  The net elimination 
in urine of acrylamide metabolites is constant in the rat and is 
independent of dose within the range 1 - 200 mg/kg body weight.  
Acrylamide has been identified in rat milk during lactation.  
There are no data indicating any major differences in acrylamide 
metabolism between man and other mammals. 

1.1.5.  Effects on man and animals

    Acrylamide is toxic and an irritant.  Cases of acrylamide 
poisoning show signs and symptoms of local effects due to 
irritation of the skin and mucous membranes and systemic effects 
due to the involvement of the central, peripheral, and autonomic 
nervous systems.  Local irritation of the skin or mucous 
membranes is characterized by blistering and desquamation of the 
skin of the hands (palms) and feet (soles) combined with blueness 
of the hands and feet.  Effects on the central nervous system are 
characterized by abnormal fatigue, sleepiness, memory 
difficulties, and dizziness.  With severe poisoning, confusion, 
disorientation, and hallucinations occur.  Truncal ataxia is a 
characteristic feature, sometimes combined with nystagmus and 
slurred speech.  Excessive sweating in the limb extremities is a 
common observation. 

    Signs of central nervous system and local skin involvement 
may precede peripheral neuropathy by as much as several weeks.  
Peripheral neuropathy can involve loss of tendon reflexes, 
impairment of vibration sense, loss of other sensation, and 
muscular wasting in peripheral parts of the extremities.  Nerve 
biopsy shows loss of large diameter nerve fibres as well as 
regenerating fibres.  Autonomic nervous system involvement is 
indicated by excessive sweating, peripheral vasodilation, and 
difficulties in micturition and defaecation.  After cessation of 
exposure to acrylamide, most cases recover, although the course 
of improvement is prolonged and can extend over months to years. 

    In animal studies, early changes in visual-evoked potentials 
(VEP), preceding clinical signs, as well as changes in 
somatosensory-evoked potentials (SEP), have been seen. 
Morphological studies have revealed degenerative changes 
principally in peripheral nerve axons, with less severe changes 
in the longer fibres of the central nervous system.  Degeneration 
of Purkinje cells has been observed in chronically-intoxicated 
animals.  The changes are most pronounced in the nerve endings of 
myelinated sensory fibres.  The nerve endings show enlarged 
"boutons terminaux" and a widespread enlargement of nerve terminals 
from the accumulation of neurofilaments.  This occurs in both the 
peripheral and central nervous systems.  Impairment of retrograde 
and, to a lesser degree, anterograde axonal transport has been 
found in sensory fibres, and interference with glycolysis and 
protein synthesis, the latter preceding the onset of clinical 
signs, has been observed in biochemical studies.  Studies of 
neurotransmitter distribution and receptor binding in the brains of 
rats have revealed changes induced by acrylamide.  In rats, changes 
in the concentration of neurotransmitters and in striatal dopamine 
receptor binding have been related to behavioural changes. 

    Degenerative changes in renal convoluted tubular epithelium 
and glomeruli and fatty degeneration and necrosis of the liver 
have been seen in monkeys given large doses of acrylamide.  In 
rats, impairment of hepatic porphyrin metabolism has been 

1.1.6.  Mutagenicity and carcinogenicity

    Acrylamide (> 99% pure) was not mutagenic in  Salmonella 
 typhimurium in the presence or absence of a metabolic activation 

    Acrylamide of unknown purity induced chromosomal aberrations 
in the spermatocytes of male mice and was reported to increase 
cell transformation frequency in Balb 3T3 cells, in the presence 
of a metabolic activation system. 

    Acrylamide was shown to be an initiator for skin tumours in 
mice when administered by various routes.  It increased the 
incidence of lung tumours in mice-screening assays. 

    A 2-year study on rats administered acrylamide in the 
drinking-water has been conducted but has not been fully reported 
or evaluated. 

    No epidemiological data on cancer due to exposure to 
acrylamide are available and, from the available data, it is not 
possible to form a conclusion concerning the carcinogenicity of 

1.1.7.  Teratogenicity and reproduction

    There is no evidence in either man or animals of any gross 
teratogenic effects resulting from acrylamide exposure. 
Absorption of acrylamide by the fetus has been demonstrated in 
animal (pig, dog, rabbit, rat) studies.  Oral administration of 
acrylamide, between the 7 - 16th days of gestation in rats, 
decreased the binding of dopamine receptors in the striatal 
membranes in 2-week-old pups, a fact that may be explained by 
postnatal exposure through lactation as well as prenatal effects.  
Degeneration of seminiferous tubules, and chromosome aberrations 
in spermatocytes have been seen in acrylamide-treated male mice.  
Depressed plasma levels of testosterone and prolactin have also 
been observed.  However, fertility studies have not been 

1.1.8.  Dose-effect and dose-response relationships

    A total of over 60 cases of acrylamide poisoning in man have 
been reported in the literature.  No human epidemiological 
studies relating exposures to effects are available; the current 
lack of methods for biological monitoring or assessing the extent 
of exposure makes such studies impossible.  From clinical 
experience, it appears that acute exposure to high doses of 
acrylamide induces signs and symptoms of effects on the central 
nervous system, whereas peripheral neuropathy is a feature of 
long-term cumulative exposure to smaller doses.  Peripheral signs 
of neuropathy appear after a latent period.  This latent period 
is dose-dependent and decreases with increasing dose.  In animal 
studies, the onset of peripheral neuropathy parallels the 
accumulation of acrylamide bound to protein in the nervous system 
and, similarly, acrylamide bound to haemoglobin in erythrocytes. 

    The LD50 was of the same order of magnitude for all mammals 

    A statistically-significant increase in the incidence of 
mesothelioma of the scrotal cavity was observed in rats after 
long-term (2-year) administration in the drinking-water of 
acrylamide at 0.5 mg/kg body weight per day.  There are no 
reports of increases in any other types of tumour at this dose 
level.  However, administration over 2 years of 2 mg 
acrylamide/kg body weight per day not only increased the 
incidence of a variety of tumour types (both benign and 
malignant) but also decreased the life expectancy in both male 
and female rats.  The smallest long-term dose of acrylamide 

reported in one study to be associated with adverse neurological 
effects in rats was 1 mg/kg body weight per day.  This dose caused 
morphological changes in the sciatic nerves. 

1.1.9.  Evaluation of health risks for man

    There are insufficient epidemiological data regarding 
occupational or environmental exposure to acrylamide to serve as 
a basis for a quantitative risk evaluation.  Experimental animal 
data indicate that there are no major species differences among 
mammals with respect to acrylamide metabolism or sensitivity to 
its neurotoxic effects.  Extrapolation from animal dose-effect 
data suggests that an absorbed dose of 0.12 mg/kg body weight per 
day (derived from total dose to surface area data) could cause 
adverse neurological effects in man.  As acrylamide is readily 
absorbed through the skin and by inhalation and ingestion, these 
effects are probably independent of the route of exposure.  
Applying a safety factor of 10 to the extrapolated minimum dose 
for neurological effects would indicate that an absorbed dose of 
0.012 mg/kg body weight per day should not be exceeded.  Animal 
data are not sufficient to draw any conclusions concerning the 
carcinogenicity of acrylamide.  Acrylamide is associated with 
adverse effects on testicular function in experimental animals.  
No data regarding these effects in human beings are available. 

    Biological monitoring would be the method of choice in the 
assessment of human exposure to acrylamide, particularly as skin 
absorption is the major route of exposure.  So far, no such 
method has been devised, though results of experimental animal 
studies indicate that the level of acrylamide bound to 
erythrocytes in blood is a measure of the absorbed dose. 

    The most suitable method for the early assessment of adverse 
effects in human beings exposed to acrylamide is the 
electrophysiological examination of peripheral nerves, such as 
measurements of both sensory and motor nerve action potential 
amplitudes and electromyography (EMG).  The sensitivity of this 
method is strongly enhanced if pre-exposure baseline measurements 
have been performed.  Quantitative assessment of vibration 
sensation offers considerable promise as a sensitive and easily 
applicable method.  The results of experimental animal studies 
indicate that other electrophysiological procedures or parameters 
such as sensory and visual evoked potentials may also be useful. 

    Exposure of the environment to acrylamide is mainly limited 
to the contamination of water.  Grouting operations may 
contaminate drinking-water supplies.  Special precautions must 
therefore be taken to limit ground water contamination and, where 
necessary, to prevent its use as drinking-water.  Effluents from 
industries producing or using polyacrylamide, communal sewage 
plants, and from waterworks may also contaminate drinking-water 
supplies, if they are taken from polluted water sources.  The 
current limit for the acrylamide content of drinking-water in 
many countries is 0.25 g/litre.  The acrylamide content of 
drinking-water can be maintained at an acceptable level by 

limiting the amount of acrylamide monomer in the polyacrylamide 
used for water treatment to 0.05%.  Under exceptional conditions, 
swimming in water close to industrial effluents containing 
acrylamide may present a hazard. 

    Preventive measures, such as the enclosure of production 
procedures and the wearing of protective clothing, should be used 
to prevent occupationally-exposed workers absorbing more than 
0.012 mg/kg body weight per day.  The concentration in the 
workroom air should not exceed 0.1 mg/m3.  Ventilated face masks 
may be used to prevent inhalation of acrylamide.  It is possible 
that underlying neurological disease and/or the administration of 
neuroactive drugs might alter human sensitivity to acrylamide 
but, in the absence of definite evidence that this has occurred, 
no specific recommendations can be made. 

1.2.  Recommendations for Further Research

1.2.1.  Analysis

    A method for the determination of acrylamide, bound to 
haemoglobin in red blood cells, should be devised to provide a 
means for the biological monitoring of human exposure to 
acrylamide.  No methods for assessing the concentration of 
acrylamide metabolites in urine are available; such analyses 
would be useful for the assessment of recent exposure, and 
methods should be devised. 

1.2.2.  Exposure

    The development of biological monitoring methods would be 
useful in the routine screening of occupationally-exposed 

1.2.3.  Metabolism and indicators of exposure

    To evaluate fully the health effects and risks associated 
with acrylamide exposure, it is important to elucidate the 
mechanism of neurotoxicity.  Both the proximal toxic agent and 
the primary biochemical lesion need to be identified.  Studies 
should be carried out to investigate further the relationship 
between the concentration of the toxic moiety in the central 
nervous system and possible indicators of exposure, such as the 
concentration of erythrocyte-bound acrylamide or metabolites in 
the urine. 

1.2.4.  Effects

    Further studies on animals are required to establish the no-
observed-adverse-effect levels for morphological changes in the 
central nervous system and to assess the carcinogenic potential 
of acrylamide. 

    Provided that methods for the biological monitoring of 
acrylamide exposure can be devised, epidemiological studies 
should be performed to relate exposure to both neurological 
effects and to the incidence of cancer in acrylamide-exposed 
workers.  Electrophysiological methods, such as the measurement 
of visual and sensory-evoked potentials, that have proved to be 
useful in experimental animal studies, should be evaluated in 
human studies.  More experience is needed in assessing the 
sensitivity and value of quantitative sensory testing.  Further 
studies should be performed to design suitable procedures for the 
health monitoring of an occupationally-exposed population.  
Further animal studies are needed on the effects of acrylamide on 
the developing nervous system and the process of ageing. 


2.1.  Identity

Chemical structure:         H   H   O   H
                            |   |   ||  |
                            C = C - C - N
                            |           |
                            H           H

Chemical formula:           C3H5NO

Synonyms:                   acrylic amide, akrylamide, propen-
                            amide, propenoic acid amide

CAS registry number:        79-06-1

RTECS registry number:      AS 3325000

Relative molecular mass:    71.08

2.2.  Chemical and Physical Properties

    Acrylamide is a white, odourless, crystalline solid that is 
highly soluble in water and reacts through its amide group or 
double bond.  Reactions of the amide group include hydrolysis, 
dehydration, and alcoholysis.  The Diels-Alder reaction, 
polymerization, and the addition of nucleophilic reactants across 
the conjugated ethylenic bond are characteristic reactions.  The 
chemical is stable in solution at room temperature and does not 
polymerize spontaneously.  Commercial solutions of the monomer may 
be stabilized with hydroquinone, t-butylpyrocatechol,  N-phenyl-2-
naphthylamine, or other antioxidants (Windholz et al., 1976).  In 
addition to carbamoylethylation and hydrolysis to acrylic acid, 
acrylamide readily undergoes polymerization and copolymerization 
resulting in a highly cross-linked insoluble gel.  The physical 
properties of acrylamide are summarized in Table 1. 

    Polyacrylamide is a white, odourless solid, soluble in water, 
insoluble in solvents such as methanol, ethanol, and hexane, and 
at least 1% soluble in glycerol, ethyl acetate, glacial acetic 
acid, and lactic acid.  The polymer is safe in relation to both 
fire and explosion (Bikales, 1973).  Levels of residual 
acrylamide monomer in polyacrylamide range from 0.05 to 5%, 
depending on the intended use of the product (Croll et al., 

    The level of residual acrylonitrile monomer in polyacrylamide 
has been estimated to be approximately 1 mg/kg (1 ppm).  In 
addition to polyacrylamide,  N-hydroxymethylacrylamide and 
 N,N'-methylenebisacrylamide are produced commercially from 
acrylamide.  The levels of residual acrylamide in these products 
are not known. 

Table 1.  Physical properties of acrylamide
Appearance                          white crystals

Relative molecular mass             71.08

Melting point                       84.5  0.3 C

Vapour pressure                     0.009 kPa at 25 C
                                    0.004 kPa at 40 C
                                    0.09 kPa at 50 C

Boiling point                       87 C at 0.267 kPa
                                    103 C at 0.667 kPa
                                    125 C at 3.33 kPa

Heat of polymerization              19.8 Kcal/mole

Density                             1.122 g/cm at 30 C

Solubility in g/litre               acetone             631
 solvent at 30 C                   benzene             3.46
                                    chloroform          26.6
                                    ethanol             862
                                    ethylacetate        126
                                    n-heptane           0.068
                                    methanol            155
                                    water               2155
Conversion factor

1 ppm acrylamide in air = 5 mg/m3
Adapted from:  Bikales (1973).

2.3.  Sampling and Analytical Methods

    A number of sampling methods have been devised for 
acrylamide, though no one technique has proved suitable for 
collecting both aerosol and vapour.  A portable pump with a 
membrane filter has been used to collect samples of acrylamide 
aerosol, and midget fritted glass bubblers have been used for the 
determination of acrylamide vapour in air.  Silica-gel sampling 
tubes with membrane filters and midget impingers have been used 
to collect both dust and vapour, the use of midget impingers 
being more efficient than sampling tubes for vapour collection.  
However, a method for sampling gaseous acrylamide using a 
specially-designed sampling tube packed with Flucin-F as the 
solid absorbent has been reported (Suzuki & Suzumura, 1977). 

    A variety of methods has been reported in the literature for 
determining levels of acrylamide in environmental media and 
biological tissues.  Those shown in Table 2 represent the most 
sensitive and/or most widely-used methods.  Acrylamide reacts 
with diazomethane in methanol-ether solution to form a pyrazoline 
derivative that can react with 4-dimethylaminocinnamaldehyde to 

form a brightly coloured (purple) Schiff base complex (Mattocks, 
1968).  This reaction is not specific for acrylamide and is 
insufficiently sensitive for determination in environmental 

    Acrylamide can be converted to its 2,3-dibromopropionamide 
derivative for use with the electron capture detector (ECD).  For 
waste water, as little as 0.1 g acrylamide/litre (as its 2,3-
dibromopropionamide derivative) has been detected by this method 
(Croll & Simkins, 1972).  The detection limit for biological 
samples was 20 g/litre in a biological extract of 0.5 ml (Poole et 
al., 1981).  Levels of 0.1 mg acrylamide/kg (0.1 ppm) in polymer or 
impinger samples (Skelly & Husser, 1978) and 0.2 g/litre (as the 
2,3-dibromopropionamide derivative) in natural and polluted water 
samples (Brown & Rhead, 1979) can be determined by means of the UV 
detection of acrylamide after separation by high-performance liquid 
chromatography (HPLC).  Differential pulse polarography can be used 
to determine acrylamide residues in polyacrylamide with a detection 
limit of less than 1 mg/kg (1 ppm) (Betso & McLean, 1976).  Dust 
and airborne samples (collected by particle and vapour filtration 
in a water impinger) have also been analysed by this technique with 
a reported sensitivity of 0.5 g/litre in the final extract (NIOSH, 

    The gas chromatography (GC) method using the 2,3-
dibromopropionamide derivative and the selective and sensitive 
ECD are the most suitable for trace level determination of 
acrylamide in environmental and biological samples though, for 
the analysis of water samples (natural and polluted), the assay 
of the derivative by HPLC has several advantages over ECGLC.  
These include the suitability for routine analysis, speed of 
determination, and stability of the calibration curve using 
different UV lamps and columns (Brown & Rhead, 1979). 

    Methods for determining impurities found in commercial 
acrylamide (acrylate, ammonium salts, acrylonitrile, 
nitrilotrispropionamide, and butanol insolubles) have been 
described by Norris (1967). 

Table 2.  Analytical techniques for determining acrylamide concentrations in environmental media and 
biological tissues
Technique         Sensitivity     Application                  Comments                   Reference       
Titration         precision       assay of commercial          interference by acrylic    Norris (1967)   
 (bromate-         0.3%          product (sales               acid, ethyl acrylate,                      
 bromide method)                  specification)                N,N'-methylene-bis-                     
Bromination/elec- 5 g/m3         determination of             no interference reported;  NIOSH (1976)    
 tron capture gas                 acrylamide vapour in air     conversion efficiencies                      
 chromatography                                                from monomer to brominated                   
                                                               derivative unknown                            
Flame ionization  0.05 - 5 mg/m3  determination of             using sampling tube        Suzuki &           
 detector; gas    (0.01 - 1 ppm)  acrylamide vapour in air     packed with Flusin-F       Suzumura (1977)    
 chromatography                                                treated with phosphoric                       
 (FID/GC)                                                      acid), the recovery of                             
                                                               acrylamide = 82 - 86%

High-performance  0.1 mg/kg       (a) determination of acryl-  no prior separation of     Skelly & Husser         
 liquid chroma-   (0.1 ppm)       amide monomer in polyacryl-  impurities is required;    (1978)                  
 tography                         amide; (b) acrylamide in     recovery of acrylamide                              
 (reverse phase)                  wipe and impinger samples    = 96%                                              
Direct current    optimum range   determination of monomeric   interference by acrylo-    MacWilliams             
 (DC) polaro-     = 0.01 - 0.5%   acrylamide in poly-          nitrile; cationic and      et al. (1965)            
 graphy           (100 - 5000     acrylamide                   anionic species                                    

Differential      < 1 mg/kg       determination of monomeric   interference by acrylo-    Betso & McLean         
 pulse polaro-                    acrylamide in poly-          nitrile, ethyl acrylates,  (1976)                  
 graphy (DPP)                     acrylamides                  cationic and anionic                               
                                                               species; some substituted                         
                                                               acrylamides; recovery of                            
                                                               acrylamide > 90%                                   

Table 2.  (contd.)
Technique               Sensitivity     Application          Comments                    Reference         
Bromination/electron    optimum range   determination        at low concentrations       Croll & Simkins   
 capture-gas chromat-   = 0.1 g/litre  of acrylamide        (> 0.25 g/litre)           (1972)         
 ography                - 1 mg/litre    in water             analytical interferences                    
                                                             must be removed; conversion                 
                                                             to derivative varies with                   
                                                             water quality; recovery of                  
                                                             acrylamide = 34 - 66%                       
Bromination/high-       0.2 g/litre    determination of     interference by natural     Brown & Rhead   
 performance liquid                     acrylamide in        organic compounds;          (1979)          
 chromatography                         natural and          recovery of acrylamide (as                  
 (reverse phase)                        polluted water       derivative) = 70  9%                       
Colorimetry             0.1 g/ml       urine analysis       interference by aldehydes   Mattocks (1968) 
                        (0.1 ppm)                            ketones, pyrroles, indoles,                 
                                                             hydrazines, chromatic                       
Bromination/electron    20 g/litre     determination of     only suitable for           Poole et al.    
 capture-gas chromat-   (corresponding  acrylamide in        measuring unbound (free)    (1981)          
 ography                to a final      biological samples:  acrylamide; recovery of                     
                        derivatized     (a) plasma           acrylamide 80-90% (in the                   
                        extract of      (b) tissue           concentration range 10 -                    
                        0.5 ml from a       homogenates      1000 ppb)                                   
                        0.5 ml tissue                                                                    

    There is no evidence that acrylamide or its commercially 
significant derivatives are directly produced in the environment. 

3.1.  Production Levels, Processes, and Uses

3.1.1.  World production

    Acrylamide was first produced in 1893 in Germany, and 
commercial production began in 1954.  The annual production of 
acrylamide in the USA for 1979, 1980, and 1981 was approximately 
30 000, 35 000, and 37 000 tonnes, respectively.  The estimated 
production of acrylamide in Japan for 1984 was approximately 36 000 
tonnes (Kagaken Kogyo Nippo, 1980).  The Stanford Research 
Institute estimated the total annual production capacity of firms 
manufacturing acrylamide in 1982 to be 63 500 tonnes.  Conway et 
al. (1979) forecast an increase in the level of production over the 
next few years. 

3.1.2.  Production processes

    Acrylamide monomer is produced commercially by either the 
sulfuric acid hydration or the catalytic hydration of 
acrylonitrile.  Since its introduction in the early 1970s, the 
catalytic process has become the preferred process, and has been 
the only process used in the USA since 1981 (US EPA, 1981).  It 
possesses many advantages over the sulfate process in that high-
purity acrylamide is produced (99.5 - 99.9% compared with 98%), 
there are no undesirable by-products, the conversion efficiency 
is greater (97% compared with 80%), and an expensive acrylamide 
purification step is avoided (Conway et al., 1979; US EPA, 1981). 

    In the catalytic process, acrylonitrile is hydrated to 
acrylamide in the following reaction: 

    CH2 = CHCN + H2O ------------> CH2 = CHCONH2
                      70 - 120 C

This is essentially a continuous process in which unreacted 
acrylonitrile is recycled back to the reactor.  Acrylonitrile and 
the catalyst are removed from the product by evaporation and 
filtration, respectively.  The aqueous acrylamide solution 
produced requires no further treatment or purification. 
Polymerization inhibitors are not required at any stage in the 
process (Davis et al., 1976).  A typical 50% aqueous acrylamide 
solution produced by this process contains 48 - 52% acrylamide 
and a maximum of 0.05% of polymer (ECT, 1978).  Residual 
acrylonitrile has been reported at levels between 1 and 100 mg/kg 
(i.e., up to 0.01%) (US EPA, 1980a). 

    Although monomer manufacture does not generate large volumes 
of by-products, acrylamide-containing waste streams are generated 
during polyacrylamide production (Conway et al., 1979). 

3.1.3.  Uses

    The major use of acrylamide and its derivatives is in the 
production of polymers and copolymers for various purposes. In 
the USA, the only large-scale use of acrylamide, other than in 
the manufacture of polymers, is as a chemical grout; this 
consumed 1100 tonnes (3%) of domestically-produced monomer in 
1980 (US EPA, 1980a).  The relative amounts of acrylamide used in 
water treatment may vary from country to country.  The various 
uses of acrylamide monomer, domestically produced and imported, 
are summarized in Fig. 1. 


    Polyacrylamides are used as flocculents to separate solids 
from aqueous solutions in mining operations, in the disposal of 
industrial wastes, and in the purification of water supplies 
(Tilson, 1981).  The largest market for acrylamide polymers is in 
the treatment of sewage and wastewater (40% of total acrylamide 
production in 1973 in the USA) (Blackford, 1974). 

    Numerous derivatives of acrylamide appear in the literature.  
The two most commercially important are  N-hydroxymethyl-
acrylamide and  N,N-methylenebisacrylamide.  N-hydroxymethyl-
acrylamide is used in the textile industry as a cross-linking 
agent and  N,N-methylenebisacrylamide is used mainly as a 
copolymer in acrylamide grout and in the manufacture of 
photo-polymer printing plates.  Some of the minor uses of 
polyacrylamides are summarized in Table 3. 

Table 3.  Minor uses of polyacrylamides
Coal dust loss preventative            Pigment-binding resins
Coal floatation                        Polyester laminating resins
Dental fillers                         Printing pastes
Drilling fluid additives               Propellant binders
Elastomer curing agent                 Rodent repellents
Electro-refining                       Shaving creams
Emulsion stabilizers                   Soil stabilizers
Flooding agents for petroleum          Suspending agents
 recovery                              Textile resins for warp sizing,
Hair sprays                             printing, shrinkproofing, anti-
Ion-exchange polymers                   static treatments, binding non-
Leather-treating agents                 woven fabrics, improving dye
Moulding resins to increase             receptivity, increasing dimen-
 strength, raise softening temp-        sional stability of viscose
 erature, or to serve as plasti-        rayon
 cizing components                     Thickening agents
Paper additives and resins for         Gel electrophoretic separation
 faster draining, improved filler       of biochemicals
 retention, coating, sizing, wet
 and dry strength improvements
From:  US EPA (1981).

3.2.  Release into the Environment

    Acrylamide monomer may enter the environment from a number of 
sources.  Because closed systems are now used in acrylamide 
manufacture (section 3.1.2), production processes are unlikely to 
be a source of environmental contamination, except in the event 
of a leak from the reactor. 

    Contamination of water by acrylamide, discharged in effluent 
from industries using or manufacturing polyacrylamide, has been 
reported (Croll et al., 1974; Conway et al., 1979; Brown et al., 

    Another potential source is the release of acrylamide monomer 
residues from polyacrylamide flocculents used in processes such 
as sludge or conditioning of oil tailings and clarification of 
waste and drinking-waters.  Croll et al. (1974) demonstrated 
that, in many water-treatment processes, acrylamide is not 
removed (section 4.3). 

    Localized contamination may also arise from the use of 
acrylamide in grouting operations.  The technology exists for the 
 in situ cross-linking of the polymer as opposed to the monomer 
in such operations, thereby decreasing environmental exposure.  
However, it is not known to what extent this technique is 
employed (US EPA, 1980a). 

    Direct contamination from spills and leaks may also occur 
during transportation, storage, use, and disposal of either 
acrylamide or polyacrylamide (Conway et al., 1979). 

    The Dow Chemical Company has estimated that releases of 
acrylamide monomer into the environment during manufacture and 
use could amount to 95 tonnes annually.  A draft report prepared 
for the US EPA estimated a higher figure of 250 tonnes (US EPA, 

3.3.  Disposal of Wastes

    Decontamination of solid and liquid wastes containing 
acrylamide may be achieved by chemical means, e.g., using 
potassium permanganate or ozone (Croll et al., 1974) or by 
biological degradation (Davis et al., 1976; Arai et al., 1981).  
Acrylamide waste may be disposed of by incineration, provided 
nitrogen oxides are scrubbed from flue gases (HBTHC, 1981).  
However, the cost of removing a large percentage of acrylamide in 
waste streams is high. 


4.1.  Transport in the Environment

    Acrylamide and its monomeric analogues have a high mobility 
in an aqueous environment and are readily leachable in soil.  
Acrylamide may travel great distances in the ground water of deep 
rock aquifers, where biodegradability is reportedly absent 
(Conway et al., 1979).  Lande et al. (1979) found acrylamide to 
have a higher mobility (leaching) and lower rate of degradation 
in sandy soils than in clay soils.  Since grouting with acrylamide 
is recommended for sandy soils, a potential hazard for ground water 
contamination may exist.  However, no studies have been made of its 
behaviour in subsurface soil where most grouting applications take 
place.  Acrylamide is unlikely to enter and be distributed in the 
atmosphere to any significant extent, because of its low vapour 
pressure.  Biodegradation is liable to occur to some extent; 
acrylamide should not be regarded as a persistent substance, 
although its rate of degradation may vary with environmental 
conditions (Davis et al., 1976). 

4.2.  Biomagnification and Bioconcentration

    Solubility, partition coefficients, and polarity will affect 
the fate of acrylamide analogues.  Since many acrylamides are 
highly water soluble and are degraded by microorganisms (Brown et 
al., 1980c), it is unlikely that they will bioconcentrate in food 
chain organisms in significant quantities (Metcalf et al., 1973; 
Neely et al., 1974).  Log Po/w (n-octanol/water partition 
coefficient), based on methods of Hansch & Leo (1979), yields an 
approximate value of -1.65 (US EPA, 1980a).  This value indicates 
that the solubility of acrylamide in water is very high compared 
with its solubility in lipids.  Thus, it is considered that 
bioconcentration of organisms in the fatty tissues will be 
minimal.  Similarly, on the basis of its water solubility, 
biomagnification of acrylamide in the food chain is not expected 
(Metcalf et al., 1973). 

4.3.  Transformation

    A wide variety of microbes possess the ability to degrade 
acrylamide (Croll et al., 1974; Lande et al., 1979; Brown et al., 
1980a) under light or dark, anaerobic or aerobic conditions.  
However, periods of several days may elapse prior to any 
significant degradative losses (Conway et al., 1979; Brown et 
al., 1982).  An amidase-producing microorganism belonging to the 
genus  Rhodococcus (strain 10 021R), isolated from the sewage of 
an acrylamide plant, was found to convert acrylamide monomer 
(even in an acrylamide gel stabilizer) into the less toxic 
acrylic acid.  This microorganism was found to be non-virulent in 
experimental animals (even at high doses) and hence, its possible 
use in the control of environmental pollution has been suggested 
(Arai et al., 1981). 

    The residence period of acrylamide may be of the order of 
days, weeks, or months in a river of low microbial activity. 
Brown et al. (1980a) also showed that degradation rates in 
samples of river water, continuously exposed to low levels of 
acrylamide (6 - 50 g/litre), were faster than those in river 
samples not previously exposed.  Acrylamide entering a water 
course may be present for several days (Brown et al., 1980a). 
Under aerobic conditions, acrylamide has been shown to be readily 
degraded in fresh water by bacteria, with a half-life of 55 - 70 
h, after acclimatization of the bacteria to the compound for 33 - 
50 h (Conway et al., 1979).  Half-lives in estuarine or salt 
water are slightly longer (Croll et al., 1974).  Cherry et al. 
(1956) studied the effects of acrylamide (10 mg/litre) on the 
chemical oxygen demand (COD) in filtered river water.  The 
initial half-life was approximately 5 days.  When the samples were 
re-exposed to acrylamide, the COD decreased more rapidly.  Croll et 
al. (1974) monitored the concentration of acrylamide in river water 
containing acrylamide at 8 g/litre.  After a time-lag of 
approximately 100 h, the acrylamide degraded rapidly.  The addition 
of acrylamide at 10 g/litre to natural waters, which had already 
been exposed to acrylamide, resulted in a shorter time-lag and 
faster degradation rates. 

    In laboratory experiments, acrylamide was not adsorbed by 
sewage sludge, natural sediments, clays, peat, or synthetic 
resins over the pH range 4 - 10.  Therefore, removal by this 
means seems unlikely unless converted to a less polar and/or 
charged compound.  Temporary entrainment in a polymeracrylamide-
particle matrix may occur during flocculation processes, and rapid 
leaching will occur should such a matrix remain in contact with 
water for a period of time (Brown et al., 1980c).  Polyacrylamide 
is used for the conditioning of waterworks sludge.  Since 92 - 100% 
of the residual acrylamide in the polymer is leached out in the 
sludge-conditioning process, care must be taken to ensure that any 
conditioned sludge supernatant which is returned to the main flow, 
does not raise the acrylamide concentration in finished water above 
acceptable levels.  A removal rate of 75% was calculated by Croll 
et al. (1974) for an overloaded sewage works receiving an 
acrylamide effluent of 1.1 mg/litre. 

    Lande et al. (1979) found a faster rate of degradation and 
lower mobility of acrylamide in silt clay soils than in clay 
loam, loamy fine sand, or loam.  Acrylamide is recommended for 
grouting on sandy soils, in which it has a relatively low rate of 
degradation and a high mobility.  Unfortunately, no studies have 
been carried out on the behaviour of acrylamide in subsurface 
soil where most grouting applications take place. 

    The half-life of acrylamide in aerobic silt loam was of the 
order of 20 - 45 h at a concentration of 25 mg/kg and a 
temperature of 22 C, and 94.5 h at 500 mg/kg and 20 C. 
Increasing the acrylamide concentration or decreasing the 
temperature increased the half-life (Lande et al., 1979; 
Abdelmagid & Tabatabai, 1982).  The behaviour of acrylamide 

(100 mg/kg) in soil-plant systems was investigated by Nishikawa 
et al. (1979).  Acrylamide decomposed mainly by hydrolysis to 
form acrylic acid.  In upland farming conditions (aerobic 
conditions), there was a rapid decrease in total organic carbon 
(TOC), up to 15 days after application, whereas in wet-land 
(rice) conditions, the decrease was slow.  These fluctuations in 
TOC under both types of farming conditions corresponded closely 
to the changes in TOC originating from acrylamide and acrylic 
acid (Nishikawa et al., 1979). 

    Polyacrylamide may be hydrolysed, but acrylamide monomer is 
not formed in solutions.  Some photosensitized polymerization is 
possible for certain acrylamide derivatives.  However, major 
modification of the molecule as a consequence of 
chemical/photochemical reaction seems unlikely (Davis et al., 


5.1.  Environmental Levels

5.1.1.  Ambient air and soil

    The results of monitoring studies in the USA, performed near 
6 plants producing acrylamide and/or polyacrylamides, showed 
average acrylamide levels in the air of less than 0.2 g/m3, in 
either vapour or particulate form, and less than 0.02 mg/kg (0.02 
ppm) in soil or sediment samples (Going, 1978). 

5.1.2.  Water

    The Committee on New Chemicals for Water Treatment in the 
United Kingdom recommended that:  commercial polyacrylamide used in 
the treatment of drinking-water should not contain more than 0.05% 
acrylamide monomer, the average amount of polymer added to water 
should not exceed 0.5 mg/litre, and the maximum dose should not 
exceed 1.0 mg/litre (UK Ministry of Housing and Local Government, 

    Although limits have been recommended for the amount of 
polyacrylamide used in the clarification of drinking-water, much 
higher levels may be encountered in other uses, where polymers 
with a higher monomer content are used at much higher levels.  
For example, polyacrylamides used for effluent treatment may 
contain monomer levels of between 1 and 50 g/kg (Croll et al., 
1974).  If effluent from such processes were to enter water 
subsequently treated for public supply, then the acrylamide 
concentration derived from the raw water source might be higher 
than that resulting from the clarification process.  The 
acrylamide contents of effluents from several industries using 
polyacrylamide are shown in Table 4. 

    Brown et al. (1980b) did not detect any acrylamide in 
effluents from the china-clay industry, after several months of 
polymer use (analytical detection limit, 0.2 g/litre).  Croll et 
al. (1974) detected 16 g acrylamide/litre in the effluent from a 
clay pit, which resulted in an acrylamide level of 1.2 g/litre in 
the receiving stream.  Further downstream at a waterworks intake, 
this level had dropped to 0.3 g/litre. 

    Environmental monitoring at sites of acrylamide and 
polyacrylamide production in the United Kingdom and the USA 
indicates that levels of acrylamide reaching surface waters from 
industrial effluent would generally be difficult to detect below 
1 g/litre (Croll & Simkins, 1972; Going & Thomas, 1979).  A 
value of 1.5 mg/litre was recorded by Going (1978) in a small 
stream receiving effluent directly downstream from a 
polyacrylamide producing plant in the USA.  High levels have also 
been found in the vicinity of local grouting operations (Croll et 
al., 1974).  Igisu et al. (1975) reported a level of 400 mg 
acrylamide/litre in well-water in Japan that had been 
contaminated from a grouting operation 2.5 metres away. 

Table 4.  Concentrations of acrylamide in some industrial effluents
Effluent                           Acrylamide     Reference            
Colliery A; tailings lagoon         42            Croll et al. (1974)  
Colliery B; tailings lagoon         39            Croll et al. (1974)  
Colliery C; coal washing;           1.8           Croll et al. (1974)  
 effluent lagoon                                                       
Colliery/coking plant effluent      0.74          Croll et al. (1974)  
Paper mill A; treated effluent      0.47          Croll et al. (1974)  
Paper mill B; treated effluent      1.2           Croll et al. (1974)  
Clay pit                            16.0          Croll et al. (1974)  
Paper mill A & B; treated effluent  < 1.0         Brown et al. (1980b) 
Paper mill A & B; process water     < 1.0         Brown et al. (1980b) 
Paper mill C; treated effluent      14.4          Brown et al. (1980b) 
Paper mill C; process water         45.4          Brown et al. (1980b) 

    No acrylamide (detection limit 4 g/litre) was detected in 
process waters from a sewage works, either before or after 
polymer addition (Brown et al., 1980a).  In another works, 
samples of vacuum- and pressure-filtered sewage sludge, 
conditioned with polyacrylamide, were found to contain up to 0.1 
g acrylamide/litre.  On the basis of the acrylamide content and 
polymer dosage, these filtrates would have contained up to 25 g 
acrylamide/litre, had no degradation and/or adsorption occurred 
(Croll et al., 1974). 

    The fate of acrylamide monomer in waterworks sludge 
conditioning (using the polymer) was investigated by Croll et al. 
(1974).  In 2 waterworks, between 74 and 87% of acrylamide 
(residual monomer from the polymer) passed into the recovered 
water.  This water was either returned directly to the waterworks 
intake or disposed of as an effluent.  No acrylamide was detected 
by Brown et al. (1980b) in process waters from a waterworks using 
polyacrylamide for effluent treatment (detection limit 0.2 
g/litre).  The authors also investigated the effects of 
accidental polymer overdosing.  A maximum concentration of 8.6 g 
acrylamide/litre was detected in backwash water, 30 min after 
spiking with 100 times the normal polymer dosage.  The effluent 
was diluted approximately 12 times, in river water 500 metres 
downstream from the discharge (0.7 g/litre).  Such effluents 
from over-loaded water- or sewage sludge-conditioning works could 
present a hazard to water supplies taken downstream of the 
effluent discharge (Croll et al., 1974). 

5.1.3.  Food

    The US Food and Drug Administration has established a maximum 
acrylamide residue level of 0.2% (2 g/kg) for acrylamide polymers 
used in paper or paperboard in contact with foodstuffs (Bikales, 
1973).  Similarly, in the Federal Republic of Germany, the 
Federal Health Authority have recommended that the level of 

polyacrylamide used as an agent for retention (Table 3) in 
foodstuff packaging should not exceed 0.3%.  This should not 
include more than 0.2% monomer.  The use of polyacrylamides in the 
washing of pre-packed foods and vegetables and the clarification 
and stabilization of wines has been described (MacWilliams, 1973; 
Croll et al., 1974).  In the USA, polyacrylamide used in the 
washing of fruits and vegetables must not contain more than 0.2% (2 
g/kg) acrylamide monomer (IRPTC, 1983).  No data regarding the 
levels of acrylamide in foods or the potential effects that such 
contamination might have on the environment are available.  Brown 
et al. (1980b) mentioned the possibility of acrylamide consumption 
by farm animals, via feed containing industrial or sewage sludges. 

5.2.  General Population Exposure

    The general population is potentially exposed to acrylamide 
by inhalation, skin absorption, water, and by ingestion of food. 

    In the Federal Republic of Germany, the level of residual 
monomer in polyacrylamide used in hair sprays is limited to 0.01% 
(0.1 g/kg)a. 

5.3.  Occupational Exposure

    Information on occupational exposure to acrylamide is sparse.  
In 1976, NIOSH estimated that approximately 20 000 workers might 
be exposed to acrylamide in the USA; however, there is no 
indication that this figure included grouting workers and Conway 
et al. (1979) estimated that this group of workers could number 
at least 2000 by 1980.  A large number of laboratory workers are 
also potentially exposed to acrylamide during the preparation of 
polyacrylamide gels for electrophoresis.  Although exposure 
levels have not been reported for grouters, the potential for 
hazard from this use is probably greater than that from other 
uses because of the uncontrolled nature of the grouters' 

    No epidemiological studies are available, and only limited
air monitoring data (Vistron Company, USA), on acrylamide
concentrations in the workplace.  Stationary air sampling
showed acrylamide concentrations ranging from 0.1 to 0.4 mg/m3
for a control room, from 0.1 to 0.9 mg/m3 for a bagging room,
and from 0.1 to 0.4 mg/m3 for a processing area.  The sampling
was performed during an 8-h working day, and the values cited
represented weekly averages.  In another factory in the USA,
personal sampling (4 h) revealed acrylamide exposure levels of
0.76 mg/m3 and 0.52 mg/m3 for 2 packers, 0.48 mg/m3 for a
reactor operator, and 0.52 mg/m3 for a dryer operator (NIOSH,
1976).  In another factory, both personal sampling and stationary
sampling were performed during 1974-75.  Personal sampling
concentrations ranged from 0.1 to 3.6 mg/m3, with the highest
concentrations seen in the bagging area.  The median value for
all personal monitoring data was 0.6 mg/m3, while the stationary
a   Bundesministerium fr Jugend, Familie und Gesundheit, 1984.

sampling showed concentrations ranging from 0.1 to 0.3 mg/m3.
Thus, in 2 factories, the personal sampling measurements were
between 2 and 3 times higher than stationary sampling measurements
(NIOSH, 1976).

    A recommended threshold limit value/time-weighted average
(TLV/TWA) for acrylamide in workroom air is 0.3 mg/m3 and the
short-term exposure limit (TLV-STEL) is 0.6 mg/m3 (ACGIH,
1984).  Other recommended occupational exposure levels (for
acrylamide in workroom air) for various countries are shown in
Table 5.

Table 5.  Occupational exposure levels for acrylamide in workroom 
air of various countriesa
Country               Exposure limit   Category of   Notation
                      (mg/m3)          limitb 
Australia             0.3              TWAc          Sd
Belgium               0.3                            S
Finland               0.3              TWA           S
Germany, Federal      0.3              MAKe          Sf
 Republic of
Hungaryg              0.3              TWA
                      1.5              STEL
Italy                 0.3              TWA           S
Japan                 0.3              MACh          S
Netherlands           0.3              TWA           S
Sweden                0.3              TWA           S
                      0.9              STELi
Switzerland           0.3              MAC           S
United Kingdom        0.3              TWA           S
                      0.6              STEL


 (a) NIOSH/OSHA       0.3              PELj          S
 (b) ACGIH            0.3              TWA           S
                      0.6              STEL

USSRk                 0.2              MAC

Yugoslavia            0.3              TWA           S
a   From:  ILO (1980) and IRPTC (1983).
b   Category of limit:  broad definition of type of limit stated. 
    For exact meaning of terms, refer to individual country 
c   TWA (time-weighted average):  a mean exposure limit averaged 
    generally over a working day whereby, within prescribed limits, 
    excursions above the level specified are permitted, provided 
    they are compensated for by excursions below the level specified.
d   SI:  specified as a skin irritant.
e   MAK:  maximum worksite concentration.

Table 5.  (contd.)
f   S (skin absorption):  this designation refers to the potential
    contribution of cutaneous absorption either by airborne or, more
    particularly, by direct contact.
g   From:  Hungary, State Ministry of Health (1978).
h   MAC:  maximum allowable concentration.
i   STEL (short-term exposure limit):  a maximum concentration 
    allowed for a short specified duration.
j   PEL:  permissible exposure limit.
k   From:  USSR, Ministry of Health (1979).

Note:   Occupational exposure levels and limits are derived in 
        different ways, possibly using different data and expressed 
        and applied in accordance with national practices.  These 
        aspects should be taken into account when making comparisons.


6.1.  Experimental Animal Studies

6.1.1.  Absorption and distribution

    Acrylamide has been reported to induce neurotoxic effects in 
many animal species following absorption via the respiratory, 
dermal, and oral routes (Hamblin, 1956).  The absorption and 
distribution of acrylamide applied dermally to rabbits was 
studied by Hashimoto & Ando (1975).  A single 30-min application 
of a 10 - 30% aqueous solution of [1-14C]-acrylamide rapidly 
penetrated the skin (auto-radiography showed a concentration of 
14C in the hair follicles) and appeared in the blood in 2 forms, 
mainly protein-bound, and in a free water-soluble form.  About 
50% of the radioactivity in the blood was associated with the 
protein-bound fraction, 24 h after cessation of contact.  This 
value increased to about 90%, when there was daily contact with 
acrylamide (30-min duration) for 7 days.  Similar patterns of 
distribution were observed after intravenous (iv) administration.  
In rats, Hashimoto & Aldridge (1970) found that the highest 
levels of radioactivity after a single iv dose (100 mg/kg body 
weight) were in whole blood.  After 24 h, the plasma contained 
little radiolabel and  in vitro binding to haemoglobin was 
demonstrated; this suggested that the protein-bound radioactivity 
in the blood was associated with the red blood cells.  By 14 
days, the majority of free/soluble radiolabel had disappeared in 
both blood and tissues.  However, the protein-bound radiolabel 
remained at 100% and 25% of the 24-h levels in blood and tissues, 
respectively.  During the 48 h following an iv dose of [1,3-14C]-
acrylamide at 50 mg/kg (Young et al., 1979), the concentration of 
radiolabel decreased in selected rat tissues but increased in red 
blood cells to a plateau that was between 10 and 90 times higher 
than the levels in the other tissues examined. 

    Miller et al. (1982) determined the extractable fraction of 
parent acrylamide in tissues obtained from rats, at various time 
intervals after an iv dose of [14C]-acrylamide at 10 mg/kg body 
weight.  Values, which ranged from 85 to 100% at 15 min, 
decreased as time progressed (10 - 50% at 12 h and less than 1% 
after 24 h).  The extractable fraction from the blood was only 
50% at 15 min and less than 1% at 12 h.  Covalent binding of 
acrylamide to cysteine residues in rat haemoglobin was 
demonstrated by Hashimoto & Aldridge (1970) and binding occurred 
at the 4 active sulphydryl groups in the haemoglobin molecule. It 
seems likely that the non-extractable fraction  in vivo is due to 
this reaction or its metabolites.

    The only biological component that has substantial irreversible 
binding and has been found to concentrate acrylamide (as 14C) is 
the red blood cell.  Pastoor & Richardson (1981) found that 3 h 
after iv administration to rats, uptake of acrylamide by red blood 
cells was essentially complete and had plateaued.  The plateau 
level was closely correlated with dose (r2 = 0.995) and was 
determined to be 2.0  0.2% of the dose per ml of red blood 

cells.  After iv administration of 10 mg [14C]-acrylamide/kg body 
weight, the binding to erythrocytes in rats plateaued at 12% of 
the dose and accounted for essentially all of the 14C in the 
blood (Miller et al., 1982).  When acrylamide was given to rats 
(30 mg/kg body weight per day), the blood concentration rose to a 
plateau of about 400 mg/kg, on day 9 (Young et al., 1979). 

    Measurements of unbound acrylamide in the blood of rats given 
a single iv dose indicated that acrylamide is distributed 
throughout total body water within 30 min (Edwards, 1975a).  
Fetal absorption of acrylamide has been reported in various 
mammalian species demonstrating the permeability of the placenta 
(section 7.5) (Edwards, 1976a; Ikeda et al., 1983).  Miller et 
al. (1982) studied the distribution and fate of orally-
administered [14C]-acrylamide (10 mg/kg body weight) in rats.  
An absorption phase, which had peaked by the end of the first 
hour, was observed in liver, fat, kidney, and testis.  Acrylamide 
is highly soluble in water and poorly soluble in lipids.  
Concentration in particular tissues is due, either to covalent 
binding to particular proteins, or to an accumulation of 
metabolites, e.g., in the liver and kidney.  The concentration of 
radiolabel in neural tissue (brain, spinal cord, and sciatic 
nerve) did not differ significantly from that in non-neural 
tissue, except for that in red blood cells (Poole et al., 1981; 
Miller et al., 1982).  Ando & Hashimoto (1972) reported that the 
distribution of radiolabel in the sciatic nerve was 2.5 times 
greater in the distal half of this tissue.  Acrylamide has also 
been reported to concentrate in the sciatic nerve terminals, with 
accumulation taking place directly from the blood stream 
(Hashimoto, 1980).  Hashimoto & Aldridge (1970) detected a 
considerable amount of protein-bound radioactivity in the brain 
and spinal cord of rats, 14 days after a single iv dose (100 
mg/kg body weight) of [14C]-acrylamide.  They suggested that this 
finding could be significant if protein binding were involved in 
the primary lesion. 

6.1.2.  Metabolism

    The biotransformation of acrylamide has been shown to be 
mainly mediated through glutathione conjugation (Pastoor et al., 
1980; Dixit et al., 1981a; Miller et al., 1982).  Studies by 
Dixit et al. (1981a) established that the reaction of acrylamide 
with glutathione occurs by both non-enzymic and enzymic 
(catalysed by glutathione- S-transferase (GST) (EC 
reactions and occurs in both the liver and the brain.  Edwards 
(1975a) demonstrated biliary excretion of a glutathione conjugate 
of acrylamide ( S-beta-propionamido-glutathione) after iv 
administration to rats.  In studies by Miller et al. (1982), 15% 
of the dose (as total 14C) was excreted in the bile within 6 h of 
oral administration to rats; only 1% was parent acrylamide. 

    Miller et al. (1982) detected at least 4 urinary metabolites 
after the oral administration of [14C]-acrylamide to rats.  The 
major metabolite was mercapturic acid ( N-acetyl-cysteine- S-
propionamide), which accounted for 48% of the dose.  Unmetabolized 

acrylamide (2%) and 3 non-sulfur-containing metabolites (total 
14%) were also present in the urine; cysteine- S-propionamide was 
identified as a urinary metabolite by Dixit et al. (1982). 

    Glutathione conjugation is presumed to be a detoxifying 
process, since Dixit et al. (1980a) demonstrated an earlier onset 
of toxicity after depletion of hepatic glutathione stores and 
Edwards (1975b) found that the glutathione conjugate did not 
induce any neurotoxic effects.  Concurrent administration of 
methionine (involved in the synthesis of glutathione) with 
acrylamide has also been shown to reduce the neurotoxic potency 
of acrylamide (Hashimoto & Ando, 1971).  Inhibition of GST by 
acrylamide has been reported by Dixit et al. (1981b), Mukhtar et 
al. (1981), and Das et al. (1982).  Thus, acrylamide may inhibit 
not only its own detoxification, but also that of other toxic 
xenobiotics along this pathway.  Pre-exposure of rats to 
acrylamide has been shown to inhibit the biliary excretion of 
methylmercury, which requires glutathione for its 
biotransformation (Refsvik, 1978). 

    Hashimoto & Aldridge (1970) reported that 6% of an iv dose
of [1-14C]-acrylamide, was exhaled by rats as [14C]-carbon
dioxide (14CO2), for 8 h after administration.  No exhaled
14CO2 was detected by Miller et al. (1982) using
[2,3-14C]-acrylamide.  It would appear, therefore, that
acrylamide is metabolized, to a small extent, by cleavage of
the carbonyl group.  Apparently, the remaining 2-carbon
fragment is not metabolized to carbon dioxide.

    Efforts to demonstrate the role of the microsomal mixed-
function oxidase (MFO) (EC system in the 
biotransformation of acrylamide have not been successful.  There is 
evidence suggesting that, under  in vitro conditions, a reactive 
metabolite of acrylamide is formed by the MFO system, which 
inhibits aniline hydroxylase activity and cytochrome P-450 in rats 
(Ortiz et al., 1981).   In vivo studies by Das et al. (1982) also 
demonstrated a decrease in hepatic MFO enzyme levels.  Similar 
studies on mice by Nilsen et al. (1978) demonstrated a reduction in 
only one form of hepatic cytochrome P-450 (P-45047), without any 
change in the total amount of cytochrome P-450.  A reduction in 
both cutaneous and hepatic aryl hydrocarbon hydroxylase (AHH) 
activity was observed in mice following topical application of 
acrylamide (Mukhtar et al., 1981).  Edwards et al. (1978) reported 
a 15% depletion of microsomal cytochrome P-450 in rats after a 
single subcutaneous (sc) dose of acrylamide. This observation was 
accompanied by a 100% increase in liver porphyrins; there is 
evidence that reactive metabolites of allyl groups formed via 
cytochrome P-450 are responsible for the abnormal degradation of 
haem (Ortiz de Montellano & Mico, 1980). 

    SKF 525A is an inhibitor of hepatic mixed-function oxidases 
(decreased detoxification or bioactivation) while phenobarbital 
increases them (increases bioactivation and/or detoxification) 
and also induces glutathione  S-transferases (detoxification).  
Kaplan et al. (1973) reported that pretreatment of rats with SKF 

525A, to inhibit hepatic mixed-function oxidase activity, 
enhanced the neurological effects and lethality of acrylamide.  
On the other hand, acrylamide-induced changes in striatal 
dopaminergic receptors were completely prevented by SKF 525A 
(Agrawal et al., 1981a).  With regard to the effects of hepatic 
microsomal inducers on the development of acrylamide neuropathy, 
Kaplan et al. (1973) reported a significantly delayed onset of 
ataxia after ip administration of acrylamide following 
pretreatment of rats with phenobarbital (or DDT), while Edwards 
(1975b) failed to obtain similar results after oral 
administration.  Hashimoto & Tanii (1981) reported that 
phenobarbital treatment reduced neuro- and testicular toxic 
effects due to acrylamide, or selected analogues in mice.  
However, Kaplan et al. (1973) found that the delayed onset of 
neurotoxicity was accompanied by a greater degree of peripheral 
nerve injury in pretreated animals.  In studies by Tanii & 
Hashimoto (1981), phenobarbital pretreatment did not increase the 
rate of  in vitro metabolism of acrylamide, but increased the 
rate of reaction of acrylamide with glutathione by some 40%.  
Because it has not yet been established whether the biological 
effects of acrylamide are due to the parent compound or to a 
bioactivated derivative, it is difficult to interpret the results 
of these studies. 

6.1.3.  Elimination and excretion  Elimination

    Acrylamide (as total 14C) was eliminated from rat tissues
in a biphasic manner (Miller et al., 1982).  In the first 
component, the elimination half-life in most tissues was less 
than 5 h and, in the second, 8 days or less.  Testes and skin had 
slower elimination rates with initial half-lives of 8 and 11 h, 
respectively.  An interesting observation was that the 
elimination of radiolabel in neural tissue did not differ 
significantly from that in non-neural tissue. 

    The amount of 14C in blood remained constant at 12% of the 
dose for up to 7 days.  However, 14C in plasma was eliminated 
very rapidly.  The terminal elimination half-life for acrylamide 
in blood (as 14C) was reported by Pastoor & Richardson (1981) to 
be about 10 days, which is close to the figure of 13 days 
suggested by Hashimoto & Aldridge (1970). 

    In contrast to the kinetics for total 14C, the elimination of
parent acrylamide fitted a monoexponential curve.  The half-life 
of parent acrylamide in blood was 1.7 h (Miller et al., 1982), 
which is comparable with the figure of 1.9 h reported by Edwards 
(1975a).  Pastoor & Richardson (1981) estimated that the half-
life of plasma acrylamide was approximately 2.5 h.  They also 
observed that the semi-log plasma elimination curves became more 
linear as the dose increased from 2 to 20 mg/kg body weight (iv 
administration), which implied a saturation of elimination 
pathways at higher doses.  The elimination of parent acrylamide 

from tissues corresponded with that seen in the blood.  Within 24 
h, no detectable levels were found in any tissue (Miller et al., 
1982).  The conclusion is that the half-life for parent 
acrylamide in blood and tissues makes it unlikely that this form 
accumulates in the body.  Excretion

    The excretion half-life of parent acrylamide in rat urine
was 7.8 h (Miller et al., 1982) (section 6.1.1).  Using
[1-14C]-acrylamide, Hashimoto & Aldridge (1970) reported that
approximately 6% of the dose was exhaled as 14CO2.  In an
extensive study of the kinetics of both orally- and iv-administered 
[2,3-14C]-acrylamide, it was shown that the rate of elimination 
of the radiolabel in urine was independent of the route of 
administration.  Within 24 h, about two-thirds of the dose was 
excreted in the urine and three-quarters in 7 days.  Faecal 
excretion was small (4.8% in 24 h and 6% by 7 days).  Since 15% 
of the dose appeared in the bile within 6 h, acrylamide or its 
derivatives must undergo enterohepatic circulation.  Thus, 
approximately 80% of the radiolabel was excreted within 7 days 
and, of this, a very large proportion (90%) was in the form of 

    When [14C]-acrylamide was given to rats daily by gavage or
in the drinking-water at 30 mg/kg body weight per day, the daily 
excretion of radioactivity in the urine was nearly constant 
during the 14-day period (Young et al., 1979), most of the dose 
being excreted as 2 major metabolites together with a small 
amount of the parent compound.  Miller et al. (1982) reported 
that the excretion rates of radiolabel in urine, following 
administration of 1 - 100 mg acrylamide/kg body weight were 
independent of dose, implying zero order elimination kinetics.  
Excretion of both free and protein-bound [14C] acrylamide has 
been demonstrated in the milk of rats, during lactation (section 
7.5) (Walden & Schiller, 1981). 

6.2.  Human Studies

    Limited data are available on absorption, distribution, 
elimination, and metabolism in human beings, and these have 
mainly been derived from clinical observations in cases of 
poisoning.  The findings in animal studies that acrylamide is 
readily absorbed, whatever the route of exposure, is supported by 
clinical observations.  The majority of human cases of acrylamide 
poisoning reported in the literature have occurred through skin 
absorption (Fujita et al., 1961; Auld & Bedwell, 1967; Garland & 
Patterson, 1967; Morviller, 1969; Graveleau et al., 1970; 
Takahashi et al., 1971; Cavigneaux & Cabasson, 1972; Davenport et 
al., 1976; Mapp et al., 1977).  Poisoning by ingestion of 
contaminated water has also been reported (Igisu et al., 1975), 
indicating efficient gastrointestinal absorption of acrylamide.  
However, quantitative data on absorption or excretion in human 
beings are not available at present.  There are no methods for 

determining acrylamide or its metabolites in blood or excreta, 
and such methods are urgently needed.  Animal data suggest that 
the concentration of acrylamide in red blood cells might serve as 
an index of body burden of acrylamide (Edwards, 1976b; Pastoor & 
Richardson, 1981).  However, no studies are available on the 
relationship between the blood concentration of acrylamide and 
its toxic effects or on human urinary excretion of acrylamide and 
its metabolites. 


7.1.  Neurological Effects

    Regardless of species, nearly all studies on acrylamide 
intoxication involve manifestations of various degrees of 
neurotoxicity; however, it must be emphasized that polyacrylamide 
itself is not neurotoxic.  Some effects of acute acrylamide 
intoxication are shown in Table 6.  Results of experimental 
animal studies suggest that central nervous system (CNS) effects 
predominate in acute acrylamide poisoning, whereas, on repeated 
administration of divided doses, signs of peripheral neuropathy 
become more evident (Le Quesne, 1980).  The general toxicological 
profile of poisoning, following prolonged exposure to repeated 
doses, includes tremors, incoordination, ataxia, muscular 
weakness, distended bladder, and loss of weight.  In acute 
single-dose studies on cats, Kuperman (1958) described ataxic 
tremors together with severe tonic-clonic convulsions and other 
signs of diffuse central excitation.  With prolonged intoxication 
in cats, incoordination was the first malfunction observed, 
followed by limb weakness (McCollister et al., 1964; Le Quesne, 
1980).  The development of neuropathy usually begins with the 
involvement of the distal parts of limbs and slowly progresses to 
the proximal regions of the body. 

7.1.1.  Neurobehavioural effects

    Numerous investigators have used neurobehavioural techniques 
to detect and quantify the neurotoxic effects of acrylamide, 
including effects on motor and sensory function, on-going 
performance, and cognitive processes. 

    The procedures and the effects of acrylamide on neuromotor 
function in rats are listed in Table 7 according to sensitivity, 
i.e., the lowest cumulative dose required to produce a 
significant alteration.  Motor dysfunction, as measured by 
impaired rotarod performance, hind-limb splay, and hind-limb 
weakness, can be observed in the dose range 100 - 320 mg/kg.  In 
other procedures involving a conditioned motor response, such as 
food-reinforced, schedule-controlled behaviour (VI or FR), changes 
in performance have been observed in the dose range 25 - 75 mg/kg. 
Tilson et al. (1979) associated neuromuscular weakness with 
histopathological alterations, i.e., loss of fibres and axonal 
swelling in peripheral nerves, both during dosing and following 
cessation of exposure.  Other studies with mice have also shown 
that motor dysfunction can be quantified using neurobehavioural 
procedures that assess motor coordination and neuromuscular 
strength (Gilbert & Maurissen, 1982; Teal & Evans, 1982). 

Table 6.  Clinical signs of acute acrylamide intoxication in mammals
Species      Route     Dose         Mortality  Clinical signs                       Reference
                       body weight) 
Mouse        oral      100 - 1000   -          postural and motor incoordination;   Kuperman (1957)
                                               convulsions; death
Mouse        dermal    (40% sol.)   100%       50% mortality within 45 min          Novikova (1979)
Rat          oral      100 - 200    -          tremor; general weakness; death      Fullerton & Barnes
Rat          ip        100 - 1000   -          ataxia; general weakness; death      Kuperman (1958)
Rat          oral      126          0/5        slight weight loss; coma             McCollister et al.
Rat          oral      256          5/5        death within 24 h                    McCollister et al.
Guinea-pig   oral      126          1/4        tremors; pupil dilation              McCollister et al.
Guinea-pig   oral      252          4/4        death within 24 h                    McCollister et al.

Table 6. (contd.)
Species      Route     Dose         Mortality  Clinical signs                       Reference
                       body weight) 
Rabbit       sc        500          -          postural and motor incoordination;   Kuperman (1957)
                                               convulsions; death
Rabbit       oral      63           0/4        slight weight loss                   McCollister et al.
Rabbit       oral      126          1/4        tremors; pupil dilation              McCollister et al.
Rabbit       oral      252          4/4        death within 24 h                    McCollister et al.
Rabbit       dermal    500 - 1000   1/5        oedema; death                        McCollister et al.
Cat          iv or ip  65 - 70      -          postural and motor incoordination    Kuperman (1957)
Cat          iv        5000         -          general weakness; circulatory        Kuperman (1957)
                                               collapse; death
Cat          ip        100          -          unconsciousness after 24 h; severe   McCollister et al.
                                               effects or death                     (1964)
Dog          oral      100          -          convulsions; postural and motor      Kuperman (1957)
Table 7.  Summary of effects of acrylamide on motor function of rats
Test                 Route        Least effective    Reference
                                  cumulative dose   
Taste aversion       oral         10                 Anderson et al.
Food-reinforced      gavage       25                 Tilson & Squibb
 variable-interval                                   (1982)
 (VI) responding                                                
Open-field           ip           50                 Gipon et al.
 rearing                                             (1977)
Altered gait         ip           50                 Jolicoeur et al.
Food-reinforced      gavage       75                 Tilson et al.
 fixed-ratio (FR)                                    (1980)
Horizontal motor     ip           100                Gipon et al.
 activity                                            (1977)
Hind-limb            gavage       100                Tilson & Cabe
 weakness                                            (1979)
Hind-limb splay      ip           150                Edwards &
                                                     Parker (1977)
                     ip           200                Jolicoeur et al.
                     (oral)       280                Edwards &
                     diet                            Parker (1977)
Rotarod              ip           300                Gipon et al.
                     ip           320                Kaplan & Murphy
                                                     (1972); Kaplan
                                                     et al. (1973)
Inclined board       gavage       500                Fullerton &
                                                     Barnes (1966)
Running wheel        (oral)       550                Lewkowski et al.
 activity            diet                            (1978)
Motor activity       gavage       600                Tilson et al.
 (automex)                                           (1979)

    Responses associated with appetitive and/or consummatory 
behaviour have also been used to quantify acrylamide-induced 
toxicity.  Teal & Evans (1982) found that administration of 
acrylamide for 30 days produced a considerable increase in 

periodic milk-licking, even in severely intoxicated animals. 
These effects are presumed to be associated with disturbances in 
water balance (Gipon et al., 1977) and may be associated with 
alterations in thirst and hunger regulation in the hypothalamus. 

    Blunting of tactile sensitivity is recognized as an early 
effect following exposure to acrylamide; such sensory signs 
usually precede motor involvement.  Recently, Maurissen et al. 
(1983) used operant psychophysical techniques to assess vibratory 
or electrical stimuli applied to the fingertips. Monkeys dosed 
orally with 10 mg/kg acrylamide, 5 days per week, for up to 9 
weeks, were found to exhibit impaired vibration sensitivity 
before the onset of neuromuscular effects.  Sensory effects were 
evident for several months after dosing ceased.  Sural nerve 
biopsies did not reveal a clear association between loss of nerve 
fibres and degree of sensory loss.  These and other data suggest 
that vibration sensory loss is probably due to dysfunction of the 
end-organ receptors.  Spencer & Schaumburg (1977) reported that 
the generator potential of the Pacinian corpuscle was decreased 
by acrylamide exposure at a time when pathology was not evident. 

    Maurissen et al. (1983) also found that sensitivity to the 
electrical stimulus did not change, suggesting that acrylamide 
differentially affected the mechanoreceptors.  Studies on rats 
have shown that acrylamide does not markedly affect 
responsiveness to thermal stimuli, even when motor dysfunction is 
present (Pryor et al., 1983). 

    Anderson et al. (1982) studied the effects of acrylamide on 
conditioned taste aversion, considered to be due to interoceptive 
effects discernible by the animal.  Taste aversion was observed 
following a single dose of acrylamide given by gavage, suggesting 
that acrylamide can induce effects at doses much lower than those 
required to induce neurohistopathological changes, and the 
neurological substrates or processes involved may be different 
from those mediating the expression of central peripheral distal 

    Where animals survived the effects of acute poisoning, 
recovery was usually rapid and complete (Spencer & Schaumburg, 
1974b).  Similarly, after long-term poisoning, neuropathy was 
reversible, though recovery was often slow (McCollister et al., 
1964; Hopkins & Gilliatt, 1971). 

7.1.2.  Electrophysiological effects  Peripheral effects

    Various electrophysiological parameters have been used to 
help characterize the development of the lesion in acrylamide-
induced peripheral neuropathy.  Fullerton & Barnes (1966) 
administered repeated doses (20 - 30 and 10 - 14 mg acrylamide/kg 
body weight per day) to rats.  Concomitant with the appearance of 
major clinical symptoms (after 3 weeks on the high dose and 12 
weeks on the low dose), the maximal motor conduction velocity 
(MCV) was reduced significantly by about 20%.  Similar reductions 
in MCV have been reported for cats (29%) and monkeys (24%) by 
Leswing & Ribelin (1969) and dogs (11%) by Satchell et al. (1982) 
with various dosage regimens and durations of exposure.  The 
reduction in MCV has been correlated with selective degeneration 
of the fast-conducting, large-diameter fibres (Fullerton & 
Barnes, 1966; Hopkins & Gilliatt, 1971; Spencer & Schaumburg, 

    Hopkins & Gilliatt (1971) carried out serial conduction 
studies on motor and sensory nerves in baboons, given relatively 
large total amounts of acrylamide (10 or 15 mg per day for 
several months).  Conduction velocity became reduced in all 
nerves, the greatest reduction being 38% in the anterior tibial 
nerve.  This occurred when there had already been considerable 
reduction in the amplitude of the evoked muscle action potential.  
The authors also studied recovery of conduction velocity and 
action potential amplitude on cessation of intoxication.  In a 
severely affected baboon treated with 15 mg acrylamide/kg body 
weight per day for 94 days, the amplitude of the nerve action 
potentials was still reduced after 1 year, but, after 2 years, it 
had returned to 80% of normal.  The amplitude of the muscle 
action potentials of less severely affected baboons (receiving 
acrylamide at 10 mg/kg body weight per day for 89 or 115 days) 
returned to normal within 2 - 3 months. 

    Sumner & Asbury (1974) measured conduction velocities in 
single sensory nerve fibres in acrylamide-intoxicated cats. They 
reported that the earliest change was failure of muscle spindle 
(type 1a) and Golgi tendon organ (type 1b) afferent terminals to 
initiate impulses.  An important conclusion of the single fibre 
study was that no reduction in conduction velocity could be 
demonstrated in surviving nerve fibres or in the proximal parts 
of fibres that had degenerated peripherally.  These findings 
confirm the suggestion that reduction in MCV is due to 
degeneration of the largest, most rapidly conducting nerve 
fibres.  Lowndes et al. (1978) studied the changes in the 
responses of primary and secondary endings of muscle spindles 
during the early stages of acrylamide intoxication in the cat.  
They reported that the earliest detectable change was an elevated 
threshold and diminished response of muscle spindle endings, 
which occurred prior to abnormalities in neuromuscular function.  
These findings confirmed previous data that large diameter 
sensory fibres are involved early in the toxicity.  Surviving 
axons did not display any slowing of conduction velocity. 

    Von Burg et al. (1981) determined the conduction velocities 
of sensory and motor nerves, both  in vivo and  in vitro, in 
mice administered acrylamide (300 mg/kg body weight per week, 
ip).  Despite an early decrease in isolated sensory (sural) nerve 
conduction velocity, a significant reduction (13%) was not 
observed until the third week of treatment, when tibial nerve MCV 
was also reduced (20%).  Similarly, significant  in vivo  
differences in conduction velocity were not observed until the 
third week, when the conduction velocities of the sciatic-sural 
and sciatic-tibial nerves were reduced by 24% and 43%, 
respectively, although a reduced velocity of the sciatic-sural 
nerve was first observed after 2 weeks of treatment. 

    Anderson (1981) studied nerve action potentials using 
isolated sural and sciatic nerves from rats given a cumulative 
dose of 100 mg/kg body weight.  A change in the waveform of the 
sural nerve action potential and an increase in the relative 
refractory period were observed as little as 24 h after a single 
dose of 100 mg/kg body weight.  In a further study (Anderson, 
1982), no effects were observed on sciatic nerve action 
potential, amplitude, or velocity 24 h after administration of 
25 - 100 mg/kg body weight, despite a significant increase in the 
duration of the evoked muscle action potential.  The significance 
of these findings in the context of early nerve changes is not 
clear.  Central nervous system effects

    There have been relatively few electrophysiological studies 
on the central nervous system.  Kuperman (1958) found 
electroencephalographic (EEG) abnormalities in acrylamide-treated 
cats prior to the development of ataxia (Table 8).  These studies 
clearly indicated that the primary neural locus was subcortical 
and it was proposed that this locus was the mesencephalic 
tegmentum.  The effects of acrylamide on spinal cord function 
were investigated in the cat by Goldstein & Lowndes (1979).  
Animals receiving 7.5 mg acrylamide/kg body weight per day were 
observed to have a reduced unconditioned spinal monosynaptic 
reflex (MSR), when the cumulative dose reached 75 mg/kg body 
weight, with no observable signs of peripheral neuropathy. 

    Boyes & Cooper (1981) measured the far-field somato-sensory-
evoked potentials (SSEPs) in acrylamide-intoxicated rats in order 
to determine the location of dysfunction in the specific 
somatosensory pathway.  The results indicated that damage may 
have occurred throughout the ascending somato-sensory system 
without damage to cortical areas. 

Table 8.  Dose-effect relationship between EEG change and signs of acrylamide intoxication in catsa
Daily dose  Number of  Number       Days to 25%        Cumulative dose resulting in:                    
(mg/kg      cats       showing 25%  increasec    25% increaseb  Maximum    Ataxiac   First neurolog-
body                   frequency                 (range)        increasec  (mg/kg)   ical deficit
weight)                increaseb                 (mg/kg)        (mg/kg)              (range in mg/kg) 
15          5          4            4.5  2      60 - 75        86  11    95  4    75 - 105
25          9          6            3.3  25     25 - 75        71  11    104  15  50 - 100
40          6          6            2.8  29     40 - 80        80  0     80  0    40 - 80

65          5          4            1.3  7      65             65  0     65  0     65

Total       25         20
a  Adapted from:  Kuperman (1958).
b  Asynchronous high-frequency pattern.
c  Mean  percent SD.
    Short-latency somatosensory evoked potentials (SLSEP) in 
monkeys during acrylamide intoxication were studied by Arezzo et 
al. (1982).  The potential produced by activity at the rostral 
end of the fasiculus gracilis (SLSEP2) was reduced, before 
abnormalities were detected in other central tracts or peripheral 

    Electrophysiological evidence of damage to optic nerve 
components was reported by Vidyasagar (1981).  Alterations in 
visual-evoked potentials (VEPs) in female monkeys (macaque) were 
reported by Merigan et al. (1982) following short-term acrylamide 
exposure.  VEP latencies were prolonged after 20 daily doses (10 
mg/kg body weight per day), well before overt signs of toxicity 

7.1.3.  Morphological effects

    The histopathological effects of acrylamide in peripheral 
nerves were investigated by Fullerton & Barnes (1966).  At doses 
inducing clinical effects in animals (section, primary 
axonal degeneration was observed with secondary demyelination of 
the sciatic, tibial, median, and ulnar nerves (as seen in 
Wallerian degeneration).  Distal nerve segments were more 
severely affected than proximal segments.  Medium- to large-
diameter fibres (8 - 9 m) were more susceptible to degeneration.  
Hopkins & Gilliatt (1971) also reported that the longest and 
largest fibres (10 - 16 m) of both motor and sensory nerves were 
most severely affected in acrylamide-intoxicated baboons (19 
mg/kg body weight per day for 118 days).  No abnormalities were 
reported in the proximal sciatic nerve or spinal cord in animals 
exhibiting severe peripheral axonal (distal) degeneration 
(Fullerton & Barnes, 1966). 

    Ultrastructural changes in the nerves of cats, administered 
3 mg acrylamide/kg body weight per day in the drinking-water (252 - 
294 days), were studied by Schaumburg et al. (1974).  Tissue 
biopsies from hind feet, after completion of the study, showed a 
loss of all types of myelinated fibres in distal nerves.  Only a 
few small and large myelinated nerve fibres were seen in plantar 
nerve twigs and most fibres had completely degenerated (bands of 
Bungner).  Many unmyelinated nerve fibres were present.  Most of 
the muscle fibres were vacuolated and shrunken. 

    In studies by Gipon et al. (1977), significant swelling in 
terminal axons and arborizations in rat muscle were reported at a 
cumulative dose of acrylamide of 550 mg/kg body weight (50 mg/kg, 
every other day).  At this dose, 50 - 60% of large peripheral 
nerve fibres showed signs of degeneration.  No histological 
abnormalities were reported in the spinal cord, but the 
techniques employed may not have been adequate. 

    Axonal degeneration in cats given 10 mg acrylamide/kg body 
weight per day was evident by 49 days and was preceded by massive 
accumulation of neurofilaments and enlarged mitochondria in the 

peripheral nerve fibres, which were evident by 22 days (Prineas, 
1969).  Similar findings were reported in the sciatic nerves of 
adult and suckling rats (4 - 12 injections of acrylamide at 50 
mg/kg body weight, 3 doses per week), when no evidence of 
abnormalities could be seen by light microscopy (Suzuki & Pfaff, 
1973).  Accumulation of neurofilaments and invaginations of the 
axolemna have also been observed under similar conditions in dogs 
(Thomann et al., 1974; Satchell et al., 1982). 

    In a study by Schaumburg et al. (1974), morphological changes 
in the terminals of sensory and motor nerve fibres were examined 
in the paws of cats administered acrylamide intraperitoneally at 
10 mg/kg body weight per day, for 7 - 32 days.  Pacinian 
corpuscle axons in the hind feet were the first terminals to 
display degeneration.  The first change was a loss of filopod 
axonal processes, sometimes accompanied by neurofilamentous 
hyperplasia.  The axolemna disappeared and the axoplasm was 
phagocytosed by inner core cells.  Shortly afterwards, changes 
were seen in juxtaposed Pacinian corpuscles, followed by 
degeneration of primary annulospiral endings of muscle spindles, 
secondary muscle spindle endings, and motor nerve terminals, in 
that order.  All these endings accumulated neurofilaments prior 
to degeneration.  These results not only demonstrated 
ultrastructural changes prior to clinical signs, but also that 
sensory nerve terminals were more sensitive than motor nerve 
terminals.  Unmyelinated fibres in somatic nerves were observed 
to be relatively resistant to the effects of acrylamide. 

    Concurrent with axonal degeneration and secondary myelin 
breakdown, Suzuki & Pfaff (1973) reported the appearance of 
endoneural macrophages and a proliferation of Schwann cells in 
the sciatic nerves of adult rats after 26 injections  of 
acrylamide (50 mg/kg body weight, 3 doses per week).  After 4 
injections, microscopic examination revealed myelin figures in 
Schwann cells and enlarged fibres within the sciatic nerve.  These 
changes became more prominent after 8 injections.  Examination of 
nerves from rats receiving 26 injections revealed numerous axonal 
sprouts growing within the Schwann cells.  Honeycomb-like 
interdigitation of Schwann cell-axon networks was observed prior to 
hind limb weakness in acrylamide-intoxicated rats (Spencer & 
Schaumburg, 1977).  Ultrastructural observations in mice led to the 
suggestion that Schwann cell damage occurred after the onset of 
axonal demyelination (Von Burg et al., 1981). 

    Accumulation of smooth endoplasmic reticulum (SER) and other 
organelles within peripheral and central nervous system neuronal 
axons has been reported following acrylamide exposure (Cavanagh & 
Gysbers, 1981; Chrtien et al., 1981).  Such accumulation in 
tibial nerves was observed several days before the onset of 
axonal degeneration (Cavanagh & Gysbers, 1981).  The same changes 
have, however, been observed in other toxic neuropathies and are 
probably of a non-specific nature. 

    Regenerating fibres have been found in nerves of rats 
administered repeated low doses of acrylamide, as shown by the 
presence of fibres with inappropriately short internodal lengths 
for their diameter (Fullerton & Barnes, 1966).  In long-term 
acrylamide intoxication, regeneration may occur simultaneously 
with continuing degeneration, but the regeneration is severely 
retarded.  Kemplay & Cavanagh (1984) reported a prolonged 
inhibition of spontaneous sprouting from motor end-plates at the 
neuromuscular junction in female rats.  This inhibition was 
apparent 24 h after a single dose (90 mg/kg body weight) and 
lasted for 4 weeks.  Acrylamide also reduced the number and 
length of reactionary terminal sprouts following partial 

    Degeneration in large sympathetic and parasympathetic and, 
therefore, probably sensory-myelinated fibres, demonstrating the 
involvement of the autonomic nervous system in acrylamide 
neuropathy, has been observed (Post & McLeod, 1977a).  Studies in 
cats showed impaired neural control of the mesenteric vascular 
bed of a type indicating damage to post-ganglionic unmyelinated 
fibres (Post & McLeod, 1977b).  Acrylamide has been shown to 
cause megaoesophagus in greyhounds (Satchell & McLeod, 1981) due 
to impairment of mechanoreceptors, the afferent fibres of which 
pass through the vagus nerve (Satchell et al., 1982). 

    Ultrastructural changes in the cell bodies (perikarya) of 
dorsal root ganglia (DRG) in cats that had received a cumulative 
dose of 320 mg acrylamide/kg body weight subcutaneously, at 10 
mg/kg body weight per day, were studied by Prineas (1969).  A 
disturbance in granular endoplasmic reticulum (GER), a breakdown 
in polyribosomes, ribosomal dislocation, and an increase in the 
amount of electron-dense material in the cytoplasm were reported.  
Using light microscopy, Sterman (1982) detected a spectrum of 
perikaryal changes in both large and small neurons of lumbar DRG 
in rats administered a cumulative dose of acrylamide at 350 mg/kg 
body weight (50 mg/kg body weight per day).  These changes 
occurred prior to significant peripheral nerve damage and 
included nuclear eccentricity, peripherally-located Nissl bodies, 
and increased numbers of perineuronal cells.  In a further study, 
Sterman (1983) observed ultrastructural changes between days 5 
and 9 of acrylamide treatment (50 mg/kg body weight per day). 
Quantitative morphometric study revealed significant perikaryal 
modifications after 5 - 6 days of treatment, which had progressed 
by 8 - 9 days.  Qualitatively, altered profiles had nuclear 
eccentricity and capping, marked changes in mitochondrial 
morphology, and modifications of ribosomes and Nissl granules.  
Neurons that appeared normal by light microscopy often displayed 
ultrastructural changes. 

    The results of microscopic examination of the brain and/or 
spinal cord have been reported in acrylamide-intoxicated rats 
(Fullerton & Barnes, 1966), mice (Bradley & Asbury, 1970), cats 
(Kuperman, 1958; McCollister et al., 1964), dogs (Thomann et al., 
1974), and monkeys (McCollister et al., 1964).  No abnormalities 
attributable to acrylamide were reported in these studies.  

Prineas (1969) demonstrated ultrastructural changes in nerve 
fibres and boutons terminaux in the anterior spinal grey matter 
after subcutaneous injection of a cumulative dose of 320 mg 
acrylamide/kg body weight (10 mg/kg per day).  Small myelinated 
fibres frequently contained excessive numbers of neurofilaments 
associated with local fibre swelling.  Similarly, 5 - 15% of the 
boutons terminaux were enlarged and contained large numbers of 
neurofilaments. At the cervical level, in the latter stages of 
intoxication (between 32 and 49 days), there were pronounced 
changes in the gracile nucleus.  Small myelinated fibres 
displayed neurofilamentous hyperplasia, many mitochondria, dense 
body and fine granular material, and unusual tubulo-vesicular 
profiles.  Myelin degeneration and axonal abnormalities were 
rarely observed. 

    A selective and progressive loss of Purkinje cells, in the 
cerebella of