UNITED NATIONS ENVIRONMENT PROGRAMME
INTERNATIONAL LABOUR ORGANISATION
WORLD HEALTH ORGANIZATION
INTERNATIONAL PROGRAMME ON CHEMICAL SAFETY
ENVIRONMENTAL HEALTH CRITERIA 191
Acrylic Acid
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.
First draft prepared at the National Institute of Health Sciences,
Tokyo, Japan, and the Institute of Terrestrial Ecology, Monk's Wood,
United Kingdom
Published under the joint sponsorship of the United Nations
Environment Programme, the International Labour Organisation, and the
World Health Organization, and produced within the framework of the
Inter-Organization Programme for the Sound Management of Chemicals.
World Health Organization
Geneva, 1997
The International Programme on Chemical Safety (IPCS) is a joint
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of the biological action of chemicals.
WHO Library Cataloguing in Publication Data
Acrylic Acid
(Environmental health criteria ; 191)
1.Acrylates - adverse affects 2.Acrylates - toxicity
3.Environmental exposure 4.Occupational exposure
I.Series
ISBN 92 4 157191 8 (NLM Classification: QV 50)
ISSN 0250-863X
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CONTENTS
ENVIRONMENTAL HEALTH CRITERIA FOR ACRYLIC ACID
PREAMBLE
ABBREVIATIONS
1. SUMMARY AND RECOMMENDATIONS
2. IDENTITY, PHYSICAL AND CHEMICAL PROPERTIES, AND ANALYTICAL
METHODS
2.1. Identity
2.1.1. Primary constituent
2.1.2. Technical product
2.2. Physical and chemical properties
2.2.1. Physical properties
2.2.2. Chemical properties
2.3. Conversion factors
2.4. Analytical methods
2.4.1. In air
2.4.2. In industrial effluents
2.4.3. In polyacrylate materials
2.4.4. In biological samples
3. SOURCES OF HUMAN AND ENVIRONMENTAL EXPOSURE
3.1. Natural occurrence
3.2. Anthropogenic sources
3.2.1. Production levels and processes
3.2.1.1 Manufacturing process
3.2.1.2 Impurities
3.2.1.3 Other sources
3.2.1.4 Production data
3.2.2. Experimental production of acrylic
acid by bacterial isolates
3.2.3. Uses
4. ENVIRONMENTAL TRANSPORT, DISTRIBUTION AND TRANSFORMATION
4.1. Transport and distribution between media
4.2. Transformation
4.2.1. Abiotic degradation
4.2.2. Biodegradation
4.2.2.1 Aerobic biodegradation
4.2.2.2 Anaerobic biodegradation
4.2.3. Bioaccumulation and biomagnification
5. ENVIRONMENTAL LEVELS AND HUMAN EXPOSURE
5.1. Environmental levels
5.2. General population exposure
5.3. Occupational exposure during manufacture,
formulation or use
6. KINETICS AND METABOLISM
6.1. Human studies
6.2. Studies on experimental animals
6.2.1. Absorption, distribution and excretion
6.2.1.1 Oral exposure
6.2.1.2 Inhalation exposure
6.2.1.3 Dermal exposure
6.2.1.4 Intravenous administration
6.2.2. Metabolism
6.2.2.1 In vitro investigations
6.2.2.2 In vivo investigations
6.2.2.3 Metabolic pathways
7. EFFECTS ON EXPERIMENTAL ANIMALS AND IN VITRO TEST SYSTEMS
7.1. Single exposure
7.2. Irritation and sensitization
7.2.1. Eye irritation
7.2.2. Skin irritation and sensitization
7.2.2.1 Skin irritation
7.2.2.2 Skin sensitization
7.2.3. Upper respiratory tract irritation
7.3. Short-term exposure
7.3.1. Oral
7.3.2. Inhalation
7.4. Long-term exposure
7.5. Reproduction, embryotoxicity and teratogenicity
7.5.1. Reproduction
7.5.2. Embryotoxicity and teratogenicity
7.5.2.1 Oral
7.5.2.2 Inhalation
7.5.2.3 Intraperitoneal
7.6. Mutagenicity and related end-points
7.6.1. In vitro and insect studies
7.6.2. In vivo mammalian studies
7.7. Carcinogenicity
7.8. Other studies
7.9. Factors modifying toxicity
8. EFFECTS ON HUMANS
8.1. General population exposure
8.1.1. Acute toxicity
8.1.1.1 Poisoning accidents
8.2. Occupational exposure
8.2.1. Poisoning accidents
8.2.2. Effects of short- and long-term exposure
9. EFFECTS ON ORGANISMS IN THE ENVIRONMENT
9.1. Microorganisms
9.2. Aquatic organisms
9.3. Terrestrial organisms
10. EVALUATION OF HUMAN HEALTH RISKS AND EFFECTS ON THE ENVIRONMENT
10.1. Evaluation of human health risks
10.1.1. Exposure of the general population
10.1.2. Occupational exposure
10.1.3. Toxic effects
10.1.3.1 Carcinogenic and mutagenic effects
10.1.3.2 Non-cancer effects
10.1.4. Risk evaluation
10.1.4.1 Inhalation exposure
10.1.4.2 Oral exposure
10.2. Evaluation of effects on the environment
10.2.1. Exposure
10.2.2. Effects
10.2.3. Risk evaluation
11. CONCLUSIONS AND RECOMMENDATIONS FOR PROTECTION OF HUMAN HEALTH
11.1. Conclusions
11.2. Recommendations for protection of human health
12. FUTURE RESEARCH
13. PREVIOUS EVALUATIONS BY INTERNATIONAL BODIES
14. REFERENCES
RESUME ET RECOMMANDATIONS
RESUMEN Y RECOMENDACIONES
NOTE TO READERS OF THE CRITERIA MONOGRAPHS
Every effort has been made to present information in thecriteria
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Criteria monographs, readers are requested to communicate any errors
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This publication was made possible by grant number 5 U01
ES02617-15 from the National Institute of Environmental Health
Sciences, National Institutes of Health, USA, and by financial support
from the European Commission.
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The Federal Ministry for the Environment, Nature Conservation and
Nuclear Safety, Germany, provided financial support for this
publication.
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WHO TASK GROUP ON ENVIRONMENTAL HEALTH CRITERIA FOR ACRYLIC ACID
Members
Dr B.I. Ghanayem, National Institute of Environmental Health
Sciences, Research Triangle Park, North Carolina, USA
Dr D. Guth, Office of Research and Development, National Centre
for Environmental Assessment, Research Triangle Park North
Carolina, USA
Mr L. Heiskanen, Environmental Health and Safety Unit,
Department of Health and Family Services, Canberra, Australia
Mr P.D. Howe, Institute of Terrestrial Ecology, Monks Wood,
Abbots Ripton, Huntingdon, United Kingdom ( Co-rapporteur)
Dr P. Lundberg, Department of Toxicology and Chemistry,
National Institute for Working Life, Sweden ( Chairman)
Dr K. Rydzynski, The Nofer Institute of Occupational Medicine,
Lodz, Poland ( Co-rapporteur)
Dr R.O. Shillaker, Pesticides Safety Directorate, Ministry of
Agriculture, Fisheries & Food, United Kingdom
Dr S.A. Soliman, Department of Pesticide Chemistry, Faculty of
Agriculture, Alexandria University, Alexandria, Egypt
Observers
Dr M. Wooder, Rohm and Haas Uk, Ltd., Croydon, Surrey, United
Kingdom (representing the American Industrial Health Council)
Dr A. Lombard, Service Hygiène Industrielle Toxicologique, ELF-
ATOCHEM, Paris, France (representing the Centre for Ecotoxicology
and Toxicology of Chemicals)
Secretariat
Dr B.H. Chen, International Programme on Chemical Safety, World
Health Organization, Geneva, Switzerland ( Secretary)
IPCS TASK GROUP ON ENVIRONMENTAL HEALTH CRITERIA FOR ACRYLIC ACID
A WHO Task Group on Environmental Health Criteria for Acrylic
Acid met at the Institute of Terrestrial Ecology, Monks Wood,
Huntington, United Kingdom, from 16 to 19 April 1996. Dr S. Dobson
opened the meeting and welcomed the participants on behalf of the
Institute. Dr B.H. Chen, IPCS, welcomed the participants on behalf of
the Director, IPCS, and the three IPCS cooperating organizations
(UNEP/ILO/WHO). The Task Group reviewed and revised the draft
monograph and made an evaluation of the risks for human health and the
environment from exposure to acrylic acid.
Dr K. Rydzynski, the Nofer Institute of Occupational Medicine,
Poland, prepared the first draft of this monograph. Dr R.O.
Shillaker, Pesticides Safety Directorate, Ministry of Agriculture,
Fisheries and Food, United Kingdom, contributed to the preparation of
the first draft. The second draft was prepared by Dr K. Rydzynski
incorporating comments received following the circulation of the first
draft to the IPCS Contact Points for Environmental Health Criteria.
Dr D. Guth, National Centre for Environmental Protection, USA,
contributed to the preparation of the final text of the evaluation.
The meeting was chaired by Dr P. Lundberg, National Institute for
Working Life, Sweden.
Dr B.H. Chen and Dr P.G. Jenkins, IPCS Central Unit, were
responsible for the overall scientific content and technical editing,
respectively.
The efforts of all who helped in the preparation and finalization
of the document are gratefully acknowledged.
ABBREVIATIONS
ACGIH American Conference of Governmental Industrial
Hygienists
CHO Chinese hamster ovary
EC50 median effective concentration
FID flame ionization detector
GC gas chromatography
GSH reduced glutathione
GV guidance value
HPLC high performance liquid chromatography
LC50 median lethal concentration
LD50 median lethal dose
LOAEL lowest-observed-adverse-effect level
LOEL lowest-observed-effect concentration
NMR nuclear magnetic resonance
NOAEL no-observed-adverse-effect level
NOEC no-observed-effect concentration
NOEL no-observed-effect level
OSHA Occupational Safety and Health Administration (USA)
TCA tricarboxylic acid cycle
TI tolerable intake
TT toxicity threshold
UDS unscheduled DNA synthesis
1. SUMMARY AND RECOMMENDATIONS
Acrylic acid is a colourless liquid, with an irritating acrid
odour, at room temperature and pressure. The odour threshold of
acrylic acid is low (0.20-3.14 mg/m3). It is miscible with water and
most organic solvents.
Acrylic acid is commercially available in two grades; technical
grade and glacial grade. Acrylic acid polymerizes easily when exposed
to heat, light or metals, and a polymerization inhibitor is therefore
added to commercial products.
The worldwide production of acrylic acid in 1994 was estimated to
be approximately 2 million tonnes. It is used primarily as a starting
material in the production of acrylic esters as a monomer for
polyacrylic acid and salts and as a co-monomer with acrylamide for
polymers used as flocculants, with ethylene for ion-exchange resin
polymers, with methyl ester for polymers, and with itatonic acid for
other co-polymers.
Acrylic acid residues in air and other media can be quantified by
means of gas chromatographic, high performance liquid chromatographic
and polarographic techniques. The detection limits of these methods
are 14 ppm in air and 1 ppm in other media.
Acrylic acid has been reported to occur naturally in marine algae
and has been found in the rumen fluid of sheep.
Being miscible with water, acrylic acid would not be expected to
adsorb significantly to soil or sediment. Under soil conditions,
chemicals with low Henry's Law constants are essentially non-volatile.
However, the vapour pressure of acrylic acid suggests that it
volatilizes from surface and dry soil.
Acrylic acid emitted into the atmosphere will react with
photochemically produced hydroxyl radicals and ozone, resulting in
rapid degradation. There is no potential for long-range atmospheric
transport of acrylic acid because it has an atmospheric lifetime of
less than one month.
Acrylic acid may be formed by hydrolysis of acrylamide monomer
from industrial waste in soil, especially under aerobic conditions.
When released into water, acrylic acid readily biodegrades. The
fate of acrylic acid in water depends on chemical and microbial
degradation. Acrylic acid is rapidly oxidized in water and can
therefore potentially deplete oxygen if discharged in large quantities
into a body of water. Acrylic acid has been shown to be degraded under
both aerobic and anaerobic conditions.
No quantitative data on levels of acrylic acid in ambient air,
drinking-water or soil are available. However, acrylic acid occurs in
wastewater effluent from its production via the oxidation of
propylene.
No data on general population exposure are available. However,
consumers may be exposed to unreacted acrylic acid in household goods
such as water-based paints. People living in the vicinity of plants
producing acrylic acid or its esters or polymers may be exposed to
acrylic acid in the ambient air. A potential source of internal
exposure to acrylic acid may result from metabolism of absorbed
acrylic acid esters.
Inhalation and contact with skin are important routes of
occupational exposure.
Regardless of the route of exposure, acrylic acid is rapidly
absorbed and metabolized. It is extensively metabolized, mainly to
3-hydroxy propionic acid, CO2 and mercapturic acid, which are
eliminated in the expired air and urine. Owing to its rapid metabolism
and elimination, the half-life of acrylic acid is short (minutes) and
therefore it has no potential for bioaccumulation.
Although a wide range of LD50 values has been reported, most
data indicate that acrylic acid is of low to moderate acute toxicity
by the oral route and moderate acute toxicity by the inhalation or
dermal route.
Acrylic acid is corrosive or irritant to skin and eyes. It is
unclear what concentration is non-irritant. It is also a strong
irritant to the respiratory tract.
Positive and negative skin sensitization results have been
reported with acrylic acid, but it appears that the positive results
may be due to an impurity.
In drinking-water studies on rats, the no-observed-adverse-effect
level (NOAEL) was 140 mg/kg body weight per day for decreased body
weight gain in a 12-month study and 240 mg/kg body weight per day for
histopathological changes in the stomach. A chronic drinking-water
study on rats showed no effect at the highest dose tested (78 mg/kg
body weight per day). A lowest-observed-adverse-effect level (LOAEL)
of 15 mg/m3 (5 ppm) by the inhalation route was observed in mice
exposed to acrylic acid for 90 days, based on very mild nasal lesions
in females at this level. Nasal effects in rats were observed at
225 mg/m3 (75 ppm), but not at 15 or 75 mg/m3 (5 or 25 ppm).
Available reproduction studies indicate that acrylic acid is not
teratogenic and has no effect on reproduction.
Both positive and negative results have been obtained in
in vitro genotoxicity tests. An in vivo bone marrow chromosome
aberration assay gave negative results. No firm conclusions can be
drawn from an in vivo DNA binding study or from a dominant lethal
assay.
Available data do not provide evidence for an indication of
carcinogenicity of acrylic acid, but the data are inadequate to
conclude that no carcinogenic hazard exist.
There have been no reports of poisoning incidents in the general
population. No occupational epidemiological studies have been
reported.
Because acrylic acid toxicity occurs at the site of contact,
separate guidance values are recommended for oral and inhalation
exposure. Guidance values of 9.9 mg/litre for drinking-water and
54 µg/m3 for ambient air for the general population are proposed.
The toxicity of acrylic acid to bacteria and soil microorganisms
is low.
Algae are the most sensitive group of aquatic organisms studied,
with EC50 values, based on growth, ranging from 0.04 to 63 mg/litre
and a no-observed-effect concentration (NOEC) for the most sensitive
species of 0.008 mg/litre. EC50 values (based on immobilization) for
Daphnia magna are 54 mg/litre (24 h) and 95 mg/litre (48 h). Acrylic
acid is more toxic to daphnids than is the alkaline salt. Acute
toxicity studies with fish have yielded results ranging from
27 mg/litre (96-h LC50) for the rainbow trout to 315 mg/litre (72-h
LC50) for the golden orfe. The 96-h NOEC for acrylic acid toxicity to
rainbow trout was found to be 6.3 mg/litre, based on a lack of
sublethal/behavioural responses.
Because of its low octanol-water partition coefficient, acrylic
acid is unlikely to bioconcentrate in aquatic organisms. There have
been no reports of biomagnification in food chains.
No data are available concerning the effects of acrylic acid on
terrestrial organisms.
2. IDENTITY, PHYSICAL AND CHEMICAL PROPERTIES, AND ANALYTICAL METHODS
2.1 Identity
2.1.1 Primary constituent
Common name: acrylic acid
CAS name: 2-propenoic acid
CAS registry number: 79-10-7
EEC No: 607-061-00-8
DOT UN: 22-18-29
RTECS Number: AS 4375000
Synonyms: acroleic acid (Sax & Lewis, 1989)
2-propenoic acid (Sax, 1984)
vinylformic acid (Sittig, 1985)
propene acid (Sax, 1984)
ethylenecarboxylic acid
(Verschueren, 1983)
UN 2218
propenoic acid (Weast et al., 1989)
ethene carboxylic acid (IUPAC name)
Chemical formula: C3H4O2
Chemical structure:
Relative molecular mass: 72.06
2.1.2 Technical product
Acrylic acid is commercially available in two grades: technical
grade (94%) for esterification and glacial grade (98-99.5% by weight
and a maximum of 0.3% water by weight) for production of water-soluble
resins (IARC, 1979; CHRIS, 1989). Acrylic acid polymerizes easily when
exposed to heat, light or metals, and so a polymerization inhibitor is
added to commercial acrylic acid to prevent the strong exothermic
polymerization (NLM, 1989). The inhibitors that are usually used in
acrylic acid preparations are the monomethyl ether of hydroquinone
(methoxyphenol) at 200 ± 20 ppm, phenothiazine at 0.1% and
hydroquinone at 0.1%. Methylene blue at 0.5 to 1.0% and N,N'-
diphenyl- p-phenylenediamine at 0.05% can also be used (IARC, 1979;
CHRIS, 1989; OHM/TADS, 1989; BASF, 1993).
2.2 Physical and chemical properties
2.2.1 Physical properties
Acrylic acid is a colourless liquid at room temperature and
pressure (IARC, 1979; Windholz, 1983; CHRIS, 1985). It has an
irritating acrid odour and it is totally miscible with water and most
organic solvents. Some of the most important physical properties of
acrylic acid are summarized in Table 1.
Table 1. Physical and chemical properties of acrylic acid
Property Value References
Odour threshold concentration (mg/m3) 0.20-3.14 Fazzalari, 1978; Amoore & Hautala, 1983;
Ruth, 1986; Grudzinski, 1988; HSDB, 1989
Melting point (°C at 1 atm) 12.3-14.0 CHRIS, 1989; Weast et al., 1989
Boiling point (°C at 1 atm) 141.3-141.6 CHRIS, 1989; Weast et al., 1989
Flash point (°C)
open cup
closed cup 54.0-68.3 IARC, 1979; Kirk-Othmer, 1984; Sax & Lewis 1989;
46-48.5 Elf Atochem, 1992; BASF, 1994a
Autoignition temperature (°C) 390-446 IARC, 1979; HSDB, 1989; BASF, 1992; Elf Atochem, 1992
Flammable limits (%)
lower 28 HSDB, 1989
upper
Burning rate (mm/min) 1.6 CHRIS, 1989
Specific gravity (g/ml at 20°C) 1.0497-1.0511 IARC, 1979; CHRIS, 1989; Weast et al., 1989
Relative vapour density (air =1 at 20°C) 2.5 HSDB, 1989
Viscosity (mPa.s at 20°C) 1.22-1.30 BASF, 1992; Elf Atochem, 1992
Saturated concentration in air
(g/m3 at 20°C) 22.8 Verschueren, 1983
Volatility (mmHg at 20°C) 3.1; 7.76 Riddick et al., 1986
Vapour pressure (mmHg)
at 39°C 10 OHM/TADS, 1989
at 75°C 60
Table 1. (contd)
Property Value References
Henry's law constant (atm.m3/mol) 3.2 × 10-7 Singh et al., 1984
Surface tension (dyne/cm) 28.1 at 30°C Dean, 1987
Heat of fusion (cal/g) 30.03-37.03 CHRIS, 1989; Weast et al., 1989
Heat of polymerization (cal/g) -257 CHRIS, 1989
Heat of combustion (cal/g) -327 at 25°C Weast et al., 1989
Heat of vaporization (cal/g) 10.955 Weast et al., 1989
Activated carbon absorbability (g/g) 0.129 Verschueren, 1983
Partition coefficient (log Kow at 20-25°C) 0.161-0.46 Korenman & Lunicheva, 1972; GEMS, 1983; Hansch & Leo, 1987;
BASF, 1988
Dissociation constant (pKa at 25°C) 4.25 Weast et al., 1989
Critical temperature (°C) 342 CHRIS, 1985
Critical pressure (atm) 57 CHRIS, 1985
Solubility: in water and most organic completely Dean, 1987; Sax & Lewis, 1989; Weast et al., 1989
solvents (alcohol, chloroform, benzene) miscible
Refractive index (nD20-25) 1.4224-1.4185 Kirk-Othmer, 1984
Maximum absorption (nm, in methanol) 252 Weast et al., 1989
2.2.2 Chemical properties
Acrylic acid preparations containing polymerization inhibitors
are reasonably stable when stored at 15-25°C and handled according to
supplier's recommendations. Heating can cause vigorous polymerization
in some circumstances. Acrylic acid reacts readily with free radicals
and electrophilic or nucleophilic agents (Kirk-Othmer, 1984). It may
polymerize in the presence of acids (sulfuric acid, chlorosulfonic
acid), alkalis (ammonium hydroxide), amines (ethylenediamine,
ethyleneimine, 2-aminoethanol), iron salts, elevated temperature,
light, peroxides, and other compounds that form peroxides or free
radicals. In the absence of an inhibitor, peroxides are formed when
oxygen is sparged into acrylic acid. This mixture can undergo violent
polymerization if heated to 60°C (CHRIS, 1989). The mechanism of auto-
accelerating polymerization of acrylic acid in hexane-methanol
solution, which can become explosive, has been studied by Bretherick
(1985).
Acrylic acid rapidly decomposes in the atmosphere by
photochemical attack on the double bond (NLM, 1989; OHM/TADS, 1989).
Acrylic acid is corrosive to many metals but not to stainless
steel or aluminium (Kirk-Othmer, 1984; AAR, 1987).
2.3 Conversion factors
In air:
1 ppm = 3.0 mg/m3 (NLM, 1989)
1 mg/m3 = 0.33 ppm (NLM, 1989)
2.4 Analytical methods
2.4.1 In air
A summary of methods for the detection of acrylic acid in air is
given in Table 2.
Table 2. Methods for the analysis of acrylic acid in air
Sampling Analytical methods Detectiona Detection limit Comment Reference
methods
Air samples absorbed GC on a glass column FID 33 mg/ml acetone The method is Vincent &
on silica gel treated packed with 1% FFAP (lower) to significantly Guient, 1982
with p-methoxyphenol on Chromosorb T 2084 mg/ml acetone affected by high
followed by desorption (upper); this is humidity. Samples
with acetone (94% equivalent to can be stored for
recovery) concentrations ranging up to 11 days at
from 0.5 ppm to 30 ppm room temperature or
(1.5-90 mg/m3) of under refrigeration
acrylic acid in a without affecting
48-litre sample volume recovery. Recommended
as useful for
determining acrylic
acid in the
occupational
environment
Table 2. (contd)
Sampling Analytical methods Detectiona Detection limit Comment Reference
methods
Air samples Reverse phase UV detector 1 g per sample; The sensitivity of OSHA, 1981
collected by HPLC 210 nm assuming 24 litre the analytical
drawing a known sample volume, this method permits
volume of air column: 25 cm × is equivalent to sampling times
through two 4.6 mm i.d. 0.042 mg/m3 as short as
XAD-8 sampling stainless steel (0.014 ppm) 15 min. Under
tubes connected column packed conditions of
in series, with Zorbax 8 m this procedure,
followed by ODS-bound, spherical the possibility
desorption with silica particles of interference
methanol/water from acetaldehyde,
(1:1) mobile phase: acetic acid,
96:4 (V/V) acrylamide,
water/acetonitrile acrolein,
containing 0.1% by acrylonitrile,
volume phosphoric methacrylic
acid; flow rate: acid is excluded.
1 ml/min; injection Method recommended
volume: 25 litre and fully validated
retention by OSHA for acrylic
time:6 min acid determinations
in workplace air
Table 2. (contd)
Sampling Analytical methods Detectiona Detection limit Comment Reference
methods
Air is pumped HPLC equipped Conductivity 1 mg/m3 air The method is Simon et
through a florisil with Aminex HPX detector (10 litre rapid, easy and al., 1989
tube at a rate of OFH organic acid sample volume) appears suitable for
1 litre/min. The analysis column the determination
sorbent is mixed (300 mm × 7.8 mm). of acrylic acid
with water (5 ml) Eluent, 2.5 × 10-4 when present in
and 1N H2SO4 (10 µl) M benzoic acid industrial emissions
prior to injection is pumped at containing other
to the chromatographic 0.8 ml/min aliphatic acids
system
a FID = Flame ionisation detector
Air samples are collected on silica gel treated with
p-methoxyhydroquinone used as an inhibitor of polymerization
(Vincent & Guient 1982) or on XAD-8 sampling tubes (OSHA, 1981). XAD-8
sampling tubes contain solid sorbent, i.e. acrylic ester polymer, of
16-50 mesh (OSHA, 1981).
After separation with gas chromatographic (GC) technique or
reverse phase high performance liquid chromatography (HPLC), flame
ionization detection (Vincent & Guient 1982) or UV detection at 210 nm
(OSHA, 1981) are utilized, respectively. The latter method was
modified and recommended by OSHA as a fully validated method for the
determination of acrylic acid in workplace air (OSHA, 1981). This
method, when coupled with an ion suppression technique, proved
successful for the retention and separation of acrylic acid.
A retention time of approximately 6 min is obtained with a Dupont
Zorbax ODS 8-µm silica packed column and a water/acetonitrile (96:4)
mobile phase containing 0.1% (by volume) phosphoric acid. The
phosphoric acid serves to suppress the ionization of acrylic acid
resulting in the retention of the undissociated form of the molecule.
Under these conditions acrylic acid is separated from potential
interfering substances: methacrylic acid, acrylamide, acrolein,
acrylonitrile and acetic acid. Propanoic acid, a saturated precursor
of acrylic acid, can be resolved from acrylic acid in a 13-min
analysis at 1 ml/min flow rate using a 0.1% aqueous phosphoric acid
mobile phase. Detection of acrylic acid at 210 nm is approximately 100
times more sensitive than that of propanoic acid, owing to the
unsaturated nature of acrylic acid. This method permits the detection
of acrylic acid in the presence of very high levels of propanoic acid.
A third method utilizes high-performance ion-exclusion
chromatography with conductimetric detection (Simon et al., 1989). The
use of 2.5 × 10-4 M benzoic acid as the mobile phase in this method
allows the separation of acrylic acid from propionic acid and other
aliphatic acids.
2.4.2 In industrial effluents
A gas chromatographic method has been developed for the analysis
of acrylic acid and some other related pollutants present in small
quantities in the effluent from a methyl acrylate plant in India
(Singh & Thomas, 1985). In this method, effluent samples were injected
directly to the GC system without prior extraction or concentration. A
Porapak Q (4 feet × 1/8 inch I.D.) column and a FID were utilized in
this method. The experimental parameters for the analysis are: column
temperature, 165°C; injector and detector temperature, 250°C; carrier
gas, N2 at 50 ml/min; hydrogen pressure, 1.3 kg/cm2; air pressure,
2.2 kg/cm2 and injection volume, 1-10 µl. The method was found to be
sensitive for detecting acrylic acid at concentrations as low as
1 ppm.
2.4.3 In polyacrylate materials
A differential pulse polarographic method was used for the
determination of residual acrylic acid in sodium polyacrylate
polymeric systems (Husain et al., 1991). The method has the advantage
of analysing acrylic acid in trace quantities directly without
resorting to separation techniques. Sample solutions of the tested
polymers were extracted with N,N-dimethylformamide several times and
the extraction mixture was made up to 25 ml, with the solvent
tert-butyl ammonium iodide (0.02 M) in N,N-dimethylformamide
serving as the supporting electrolyte. The polarographic measurements
were performed with a Metrohm E-506 Polarecord equipped with a three-
electrode system (a dropping mercury electrode (DME), Ag/AgCl
(saturated KCl) reference electrode, and an auxiliary platinum
electrode). Using this method, free acrylic acid in polymers at levels
of 10-100 ppm can be measured with a precision of ± 3%.
2.4.4 In biological samples
Methods for the analysis of acrylic acid in aqueous samples and
tissues extracts in metabolic studies have been reported (Mao et al.,
1994; Mitchell & Petersen, 1988; Black et al., 1995). In these
methods, high-performance ion-exclusion chromatography and/or reverse
phase HPLC with radiometric, refractive index, photo diode-array and
UV detectors were used for the separation and quantification of
acrylic acid.
In another study, residues of acrylic acid in an anaerobic
degradation mixture were quantified using a gas chromatographic
technique with a flame ionization detector (FID) (Stewart et al.,
1995). The column was an 80/120 Carbopak B-DA/4% Carbowax 20 M. The
column and FID temperatures were 175 and 200°C, respectively. The
carrier gas was helium at a flow rate of 24 ml/min. The detection
limit was 1 mg/litre.
3. SOURCES OF HUMAN AND ENVIRONMENTAL EXPOSURE
3.1 Natural occurrence
Acrylic acid has been reported to occur naturally in the
following species of marine algae: 9 species of Chlorophyceae, 10
species of Rhodophyceae and 11 species of Phaeophyceae (Sieburth,
1960, Glombitza, 1970a,b, 1979). It is also produced in
Phaeodactylum tricornutum, Phaeocystis spp. and Polysiphonia
lanosa (Brown et al., 1977), as a result of hydrolysis of dimethyl-ß-
propiothetin (Verschueren, 1983).
Acrylic acid has been identified as an antibacterial substance in
oysters (Brown et al., 1977), scallops, ( Patinopecten yessoensis)
(Kodama & Ogata, 1983), and the digestive tract of penguins (Sieburth,
1960; Herwig 1978). It is thought to originate from the phytoplankton
Protogonyaulax (Kodama & Ogata, 1983), Phaeocystis spp (Sieburth,
1960) and Phaeodactylum tricornutum (Brown et al., 1977) on which
the molluscs and penguins fed. It has also been shown that under
natural conditions acrylic acid is generated by certain species of
algae and acts as a microbiocide (Glombitza, 1970a,b, 1979; Heyser &
Glombitza, 1972). It has also been identified as the agent responsible
for the antimicrobial activity of the marine algae Gracilaria
corticata and Ulva lactuca (Bandara et al., 1988).
Acrylic acid has been found in the rumen fluid of sheep as a
result of bacterial fermentation of carbohydrates (Noble & Czerkawski,
1973), where it is converted by rumen microorganisms to propionic acid
(Whanger & Matrone, 1967). It can also be produced from lactic acid by
the anaerobic rumen bacterium Megasphaera elsdenii in the presence
of 3-butynoic acid (Sanseverino et al., 1989).
Acrylic acid has been found in agricultural rum obtained by
fermentation of sugarcane juice by the action of Micrococci spp
(Ganou-Parfait et al., 1988).
3.2 Anthropogenic sources
3.2.1 Production levels and processes
3.2.1.1 Manufacturing process
The first commercial process for the manufacture of acrylic acid
and its esters involved hydrolysis of ethylene cyanohydrin in sulfuric
acid. This route is no longer commercially significant (Kirk-Othmer
1984).
Most commercial acrylic acid is now produced via a process in
which propylene is vapour-oxidized to acrolein, which is in turn
oxidized at 300°C with molybdenum-vanadium catalyst to acrylic acid
(NLM, 1989). Other methods of production are as follows:
* a modification of the Reppe process by the reaction of acetylene,
carbon monoxide and alcohol with a nickel catalyst;
* by hydrolysis of acrylonitrile;
* condensation of ethylene oxide with hydrocyanic acid followed by
reaction with sulfuric acid at 160°C;
* a process in which formaldehyde undergoes a type of aldol
reaction with a large molar excess of acetic acid in the vapour
phase in a catalyst tube containing calcium Decalso (Kirk-
Othmer, 1984);
* a heterolytic dehydration pathway of lactic acid in supercritical
water (Mok et al., 1989).
3.2.1.2 Impurities
Commercial acrylic acid is available in two grades: technical and
glacial. Glacial grade is 98-99.5% acrylic acid (NLM, 1989). This may
contain, as impurities, water up to 0.3% w/w and acrylic acid dimer up
to 0.1% w/w (BASF, 1992; Elf Atochem, 1992).
3.2.1.3 Other sources
Acrylic acid has also been detected in trace amounts in
commercial propionic acid (Kostanyan et al., 1969).
3.2.1.4 Production data
Available data on the production of acrylic acid are shown in
Table 3.
Table 3. Production data
Country Year Production of Reference
acrylic acid
(in kilotonnes)
China 1994 105 CEFICA (1995)a
European Community 1975 155 IARC (1979)
1994 665 CEFIC (1995)a
Japan 1976 70 IARC (1979)
1994 420 CEFIC (1995)a
Korea 1994 60 CEFIC (1995)a
Taiwan 1994 50 CEFIC (1995)a
USA 1993 332 US ITC (1983)
1985 361 US ITC (1985)
1986 348 US ITC (1986)
1987 499 US ITC (1987)
1988 480 US ITC (1988)
1991 554 NLM (1991)
1994 685 CEFIC (1995)a
a Submission of the European Council of Chemical Industry
Federations (CEFIC) to the European Union Chemicals risk
assessment document.
The worldwide production of acrylic acid was approximately
1.13 million tonnes in 1991 (Chemical Marketing Reporter, 1992).
Worldwide capacity for acrylic acid production was reported to be
2 million tonnes in 1994 (CEFIC, 1995).
3.2.2 Experimental production of acrylic acid by bacterial isolates
The following bacterial species have been utilized in
experimental systems to produce acrylic acid:
* from acrylonitrile: (1) by the action of epsilon-caprolactum-
induced Rhodococcus rhodochrous J1 (Nagasawa et al., 1990);
with a periodic substrate feeding system the highest accumulation
(390 g/litre) was obtained; (2) by Arthrobacter sp. isolated
from petrochemical industry waste (Narayanasamy et al., 1990).
* from acrylamide by the action of Pseudomonas sp. and
Xanthomonas maltophilia isolated from herbicide-contaminated
soils (Nawaz et al., 1993, 1994); batch culture of these bacteria
completely degraded 62.8 mM acrylamide to acrylic acid and
ammonia in 24 and 48 h, respectively.
3.2.3 Uses
Acrylic acid is used primarily: as a starting chemical for ethyl
acrylate, n-butyl acrylate, methyl acrylate, 2-ethylhexyl acrylate;
as a monomer for polyacrylic acid and salts, cross-linked high (and
low) molecular weight polymers; as a co-monomer with acrylamide for
polymers used as flocculants; with ethylene for ion-exchange resin
polymers; with methyl ester for polymers; and with methylene succinic
acid (itaconic acid) for other co-polymers (SRI, 1981; NLM, 1989).
In 1987, 25% of the acrylic acid produced in the USA was used for
surface coatings; 20% for polyacrylic acid and salts, including super-
absorbent polymers, detergents, water treatment and dispersants; 13%
for textiles and non-wovens; and 9% for adhesives and sealants
(Kavaler, 1987).
Until 1979, in the European Union countries more than 80% of
acrylic acid was used for the production of polyacrylates and in Japan
90% was used in the production of acrylic esters (IARC, 1979). In
1988, European use of acrylic acid was 69% for esters, 10% for
detergents, 8.5% for flocculants and dispersants and 6.5% for super-
absorbers (CEFIC, 1995).a
a Submission of the European Council of Chemical Industry
Federations (CEFIC) to the European Union chemicals risk
assessment document.
Other uses are in the production of copolymers for dental
adhesives (Bowen, 1979), in the production of hydrogels used for
contact lenses (Kirk-Othmer, 1984), in surface coating formulations
(Kirk-Othmer, 1984), and in latex applications to increase stability
in order to prevent premature coagulation (Kirk-Othmer, 1984).
4. ENVIRONMENTAL TRANSPORT, DISTRIBUTION AND TRANSFORMATION
4.1 Transport and distribution between media
Acrylic acid is miscible with water (Riddick et al., 1986) and
therefore would not be expected to adsorb significantly to soil or
sediment (Lyman et al., 1982). The Henry's Law constant for acrylic
acid is reported to be 3.2 × 10-7 atm m3/mol (Singh et al., 1984).
Under soil conditions, chemicals with such low Henry's Law constants
are essentially non-volatile (Lyman et al., 1982). However, the vapour
pressure of acrylic acid suggests that it volatilizes from surface and
dry soil (Howard, 1991).
The adsorption and desorption of acrylic acid were examined in
five different soils: an aquatic sandy loam sediment, a loamy sand, a
clay loam and two loams. The average Koc for the adsorption of
acrylic acid to soil was 43, and ranged from 23 to 63. The Koc values
for the desorption data were widely scattered with values ranging from
18 to 837. This indicates that the degree of adsorption is not
correlated to the organic carbon content (OC), which ranged from 0.46%
for the loamy sand to 4.58% for one of the loams. The results of this
study indicate a high mobility of acrylic acid through soil (Archer &
Horvath, 1991).
Using the fugacity model of Mackay & Peterson (1981) the
theoretical distribution of acrylic acid has been estimated. About 97%
of acrylic acid released to the environment should be associated with
the aquatic environment (the water phase), approximately 1.6% in air,
1% in sediment and < 1% in soils, suspended solids and biota
(Staples, 1993).
Since the atmospheric lifetime of acrylic acid is less than one
month (Atkinson, 1987), there is no potential for long-range transport
of this compound.
4.2 Transformation
4.2.1 Abiotic degradation
The UV absorption band of acrylic acid extends to about 320 nm
(Weast & Astle, 1985). Vapour phase acrylic acid reacts with
photochemically produced hydroxyl radicals primarily by addition to
the double bond and with atmospheric ozone, resulting in an estimated
overall half-life of 6.6 h to 6.5 days (Atkinson & Carter, 1984).
Based upon the estimated rate constant for vapour phase reactions and
assuming hydroxyl radical concentrations of 5 × 105 radicals per cm3
and an ozone concentrations of 7 × 1011 molecules per cm3 (Atkinson
and Carter, 1984; Atkinson, 1987), a half-life of 2.5-23.8 h was
estimated by Howard et al. (1991).
Acrylic acid was found to be stable to hydrolysis at pH values
between 3.7 and 11 (Shah, 1990).
4.2.2 Biodegradation
4.2.2.1 Aerobic biodegradation
When added to water, acrylic acid is rapidly oxidized, and
wastewater containing the compound can deplete reservoirs of oxygen
(Ekhina & Ampleeva, 1977).
Several biodegradability studies show that acrylic acid will
readily biodegrade (Lyman et al., 1982; Keystone Environmental
Resources, 1989a; Douglas & Bell, 1992). The BOD5 (biological
oxygen demand, 5 days) for glacial acrylic acid, using acclimated,
fresh dilution water and raw sewage from a local treatment plant as
the inoculum, was determined to be 0.315 g of oxygen consumed per gram
of product. The COD (chemical oxygen demand) under the same conditions
was 1.48 g/g (Keystone Environmental Resources, 1989)a; therefore,
the BOD5/COD ratio was 0.21. A BOD5/COD ratio of 0.26 was also
reported by Lyman et al. (1982). Biodegradation of acrylic acid in a
14-day BOD test was up to 68% (CITI, 1992). Acrylic acid at a
concentration of 3 mg/litre attained 81% biodegradation within 28 days
in a closed-bottle test based on the consumption of oxygen (Douglas &
Bell, 1992). The pass level of 60% was reached within 10 days of
exceeding the 10% level, and so acrylic acid is considered to be
"readily biodegradable" according to EC classification criteria (EEC,
1988).
The metabolism of 14C-acrylic acid in sandy loam soil has been
studied under aerobic conditions for up to 28 days after treatment at
a rate of 100 mg/kg. Acrylic acid was rapidly metabolized; after 3
days no acrylic acid was detected in soil extracts. Carbon dioxide
evolution accounted for 72.9% of applied radioactivity by day 3 and a
total of 81.1% over the 28-day study period. The half-life for acrylic
acid under these conditions was estimated to be less than 1 day
(Hawkins et al., 1992).
Acrylic acid formed from hydrolysis of acrylamide added to soil
was totally degraded within 15 days of its formation (Nishikawa et
al., 1979). In a 42-day screening study using a sewage seed inoculum,
71% of acrylic acid was mineralized under aerobic conditions. After
previous acclimatization, 81% of acrylic acid degraded to carbon
dioxide in 22 days (Pahren & Bloodgood 1961; Chou et al., 1978).
a Report sent by J.M. Flaherty to J. McLanghlin, Rohm and Haas
Spring House (work order numbers M8903002 and M8902005).
A collection of strains utilizing acrylonitrile, acrylamide and
acrylic acid as sole carbon and/or nitrogen source was isolated from
environmental samples. Strains with maximum decomposing activity were
identified as Pseudomonas pseudoalcaligenes 6p; P.alkaligenes 5g
and Brevibacterium spp. 13 PA (Moiseeva et al., 1991).
An aerobic gram-negative bacterium ( Pseudomonas sp.) isolated
from tropical garden soil was found to be able to degrade a high
concentration of acrylamide (4 mg/litre) to acrylic acid and ammonia,
which were utilized as sole carbon and nitrogen sources, respectively,
for growth (Shanker et al., 1990).
A strain of Byssochlamys sp. produced ß-hydroxypropionic acid
(ß-HPA) when grown on media containing high concentrations of acrylic
acid. The maximal production of ß-HPA was 4.8% when the initial
culture medium contained 7% acrylic acid and 2% glucose and the
initial culture pH was adjusted to 7.0 (Takamizawa et al., 1993).
Acrylic acid has been reported to be significantly degraded
(> 30%) in the MITI test, a biodegradability screening test of the
Japanese Ministry of International Trade and Industry (Sasaki, 1978).
Acrylic acid was completely degraded in a standard Zahn-Wellens test
and the authors concluded that it is biodegradable (BASF, 1993).
Acrylic acid has been found to be degraded by a strain of
Alcaligenes denitrificans isolated from a landfill soil. The
bacterium degraded acrylic acid through the intermediate formation of
L-(+)-lactic and acetic acids, which were further metabolized
(Andreoni et al., 1990).
4.2.2.2 Anaerobic biodegradation
Speece (1983) reported that acrylic acid can undergo ultimate
anaerobic biodegradation. In an anaerobic screening study utilizing
10% sludge from a secondary digester as an inoculum, acrylic acid was
judged to be degradable, with over 75% of theoretical methane being
produced within 8 weeks of incubation (Shelton & Tiedje, 1984).
In another study, acrylic acid was toxic to unacclimated
anaerobic acetate-enriched cultures and was poorly utilized (21%) in a
completely mixed anaerobic reactor with a 20-day hydraulic retention
time after a 90-day acclimatization period (Chou et al., 1978). A
possible explanation for the conflicting results of anaerobic
degradation is the observation that acetate cultures have to exhaust
the acetic acid as carbon and energy source before they can utilize a
cross-fed compound (Chou et al., 1978).
The biodegradability of acrylic acid using methanogenic acetate
enrichment culture was studied by Stewart et al. (1995). Acrylic acid
was degraded with almost no effect on methanogens with spikes up to
100 mg/litre. However, concentrations of 500, 1000 and 1500 mg/litre
were found to inhibit the methanogens for several days before
recovery. Acrylic acid was eventually degraded to less than 1 mg/litre
(> 99% of initial concentration) in all cases by the end of the
study (55 days).
4.2.3 Bioaccumulation and biomagnification
From the low value for log Kow, ranging from 0.161 to 0.46
(Hansch & Leo, 1987; BASF, 1988), one would expect the
bioconcentration of acrylic acid in organisms to be negligible Bysshe
(1990) using a regression equation calculated theoretical
bioconcentration factors ranging from 0.78 to 1.3. Veith et al. (1979)
estimated the bioconcentration factor to be in the range of 1.6 to
2.4.
There have been no reports of biomagnification of acrylic acid in
the food chain.
5. ENVIRONMENTAL LEVELS AND HUMAN EXPOSURE
5.1 Environmental levels
No quantitative data are available for environmental levels of
acrylic acid in ambient air, water or soil. Acrylic acid has been
found to occur naturally in some marine algae (Sieburth, 1960; Brown
et al., 1977) and some molluscs (Kodama & Ogata, 1983). The acrylic
acid content of Phaeocystis spp. can be 7.4% of dry weight
(Sieburth, 1960). Other marine algae have been found to contain
acrylic acid: Chlorophyceae, 0.124-16.5 mg/g dry weight;
Rhodophyceae, 0-0.131 mg/kg dry weight; and Phaeophyceae 0-0.02 mg/g
dry weight (Glombitza, 1970a, 1979).
5.2 General population exposure
No data are available for general population exposure. However,
consumers may be exposed to unreacted acrylic acid in the following
household goods: polishes, paints and coatings, adhesives, rug
backing, plastics, textiles and paper finishes (USEPA, 1981).
Information on the typical content of unreacted acrylic acid in these
kinds of products is unavailable.
Populations living in the vicinity of plants producing acrylic
acid or manufacturing its esters or polymers may be exposed to acrylic
acid in the ambient air. The concentrations of emitted vapours of
acrylic acid in the plume from such plants were found to vary from 22
to 183 mg/m3 (Grudzinski, 1988). However, there are no data on
concentrations of acrylic acid in the ambient air of populated areas.
Acrylic acid occurs in wastewater effluents from its production
by the oxidation of propylene at concentrations not exceeding
0.5 mg/litre (Wise & Fahrentholdt, 1981). After treatment of
wastewater from a production facility in Europe, acrylic acid levels
were below the limit of detection (0.1 mg/litre) (CEFIC, 1995)a.
However, effluent from a methyl acrylate plant in India was found to
contain 2500 mg/litre as acrylic acid (Singh & Thomas, 1985).
a Submission of the European Council of Chemical Industry
Federations (CEFIC) to the European Union chemicals risk
assessment document.
Since there is evidence that acrylic acid esters are hydrolysed
to acrylic acid in laboratory animals (Ghanayen et al., 1987) and in
human tissues in vitro (Wiegand, 1990), a potential source of
internal exposure to acrylic acid may result from metabolism of
absorbed acrylic acid esters (Frederick et al., 1994; Sanders et al.,
1988).
5.3 Occupational exposure during manufacture, formulation or use
Occupational exposure is the most important means of human
exposure to acrylic acid. Inhalation and contact with skin are
important routes of exposure.
The National Institute of Occupational Safety and Health (NIOSH)
conducted two observational nationwide surveys, a decade apart, to
determine the extent of exposure of workers to a variety of substances
in their work environment. The National Occupational Hazard Survey
(NOHS) was conducted during 1972-1974 using a stratified probability
sample of 4636 businesses in 67 metropolitan areas throughout the USA
employing nearly 900 000 workers (NIOSH 1974, 1977). According to the
NOHS, an estimated 28 600 workers were potentially exposed to acrylic
acid, approximately 10% of whom were exposed to acrylic acid and 90%
to trade-name products. However, this estimation excluded the exposure
of the general population to trade-name chemicals possibly containing
acrylic acid. Acrylic acid was seen in 16 major industry groups and in
41 occupational groups in the NOHS.
During 1981-1983 NIOSH conducted the National Occupational
Exposure Survey (NOES), using a stratified probability sample of 4490
businesses in 98 different geographic locations of the USA employing
nearly 1.8 million workers (NIOSH, 1990). According to the NOES, an
estimated 96 500 workers were potentially exposed to acrylic acid,
approximately 10% of whom were exposed to acrylic acid and 90% to
trade-name products. Acrylic acid was seen in 25 major industry groups
and in 67 occupational groups (NIOSH, 1990).
One study conducted at a large manufacturing facility of the Rohm
and Haas Company in the USA, where several chemicals including acrylic
acid and a variety of acrylates and methacrylates were used, indicated
that ethyl acrylate and acrylic acid levels varied from 0.01 to
56 ppm. Most areas of the plant had levels (as 8-h time-weighted
averages) well below the hygiene standards recommended at that time by
the OSHA and the ACGIH of 10 ppm for acrylic acid and 5 ppm for ethyl
acrylate (ACGIH, 1988, OSHA, 1989). Many of the available industrial
hygiene data were specific for high, short-term exposure tasks
(5-40 min samples) when chemicals were pumped into containers for
shipping or when lines were open for new connections, or to obtain
samples. They revealed levels at the high end of the above-mentioned
range (Schwartz et al., 1989).
Exposures of workers to acrylic acid for short periods of time of
less than 15 min and for full shift expressed as time-weighted average
(TWA) concentration have been compiled from four producing companies.
Operators had a mean short-term exposure limit (STEL) value of
8.4 mg/m3 (range < 0.3 to 189 mg/m3); loading/unloading operations
a mean of 3.9 mg/m3 (range 1.2 to 12 mg/m3); and those engaged in
quality assurance a mean of 0.3 mg/m3 (range of less than 0.3 to
0.6 mg/m3). Concerning the 8-h TWA, the operators showed levels of
0.48 mg/m3 (range of 0.03 to 3 mg/m3) and loading/unloading
operations a mean of 0.39 mg/m3 (range of 0.27 to 1.98 mg/m3)
(Casciery & Clary, 1993).
No such data are available from other countries.
6. KINETICS AND METABOLISM
6.1 Human studies
Apart from in vitro skin absorption studies, no data are
available on kinetics, metabolism or elimination or acrylic acid in
humans.
The absorption of 14C-acrylic acid (site of label unspecified)
dissolved in acetone, water or phosphate buffer (pH 6.5) was tested
using samples of excised (postmortem) human and mouse skin in vitro
(Corrigan & Scott, 1988). Acrylic acid concentrations of 0.01, 0.1,
1.0 and 4.0% were applied at 100 µl/cm2 under occlusive conditions.
Samples were taken from the receptor fluid up to 32 h. Rates of
absorption decreased in the order of magnitude as follows: acetone >
water > phosphate buffer. Independent of the vehicle, the absorption
rate increased as a function of acrylic acid concentration.
Permeability coefficients, which ideally are concentration-independent
expressions of absorption rate, for human skin ranged from 0.37 to
0.72 × 10-3 cm/h for water and from 0.47 to 1.81 × 10-4 cm/h for
phosphate buffer. Permeability coefficients were not calculated for
acetone because of evaporation of this volatile vehicle during the
course of the experiments (Corrigan & Scott, 1988).
A briefly reported in vitro percutaneous penetration study
using excised human cadaver skin indicated that 14C-acrylic acid
absorption can vary significantly as a function of pH and delivery
vehicle. In vitro flux, estimated after a 1 mg dose was applied,
varied by 600 times within the treatments studied and decreased in the
order: acetone (600 µg/cm2 per h) > phosphate buffer pH 6.0
(23 µg/cm2 per h) > ethylene glycol (15 µg/cm2 per h) > phosphate
buffer pH 7.4 (1 µg/cm2 per h) (D'Souza and Francis, 1988).
6.2 Studies on experimental animals
6.2.1. Absorption, distribution and excretion
6.2.1.1 Oral exposure
After oral gavage administration of an aqueous solution of
(1-11C)-acrylic acid (26 µg/kg body weight) to female Sprague-Dawley
rats, it was rapidly absorbed and expired mainly as 11CO2 within 1 h
post-administration. The uptake appeared biphasic. The short alpha-
phase had an apparent first-order absorption constant (Ka) of 19% of
the available dose per minute (biological half-time = 3.6 min) and the
Ka of the ß-phase was 30% (biological half-time = 23 min). Relative
retention of radiolabel (dpm per g tissue versus dpm per g body
weight) after 65 min was above unity in liver (2.6), adipose tissue
(1.9), small intestine (1.5), kidneys (1.2) and spleen (1.0).
Approximately 6% of the radiolabel was excreted in the urine within
65 min (Kutzman et al., 1982).
In another study, single gavage doses of 4, 40 or 400 mg/kg body
weight of (2,3-14C)-acrylic acid in 0.5% aqueous methylcellulose
solution were administered to male Sprague-Dawley rats. Approximately
35, 55 and 60%, respectively, of the administrated dose were
eliminated, mostly as 14CO2, within 8 h. By 24 h 50-65% of the dosed
radioactivity was eliminated and the excretion of radioactivity had
virtually ceased. After 72 h, 44-65% of the administrated
radioactivity had been eliminated as 14CO2; 2.9-4.3% in urine, 2.4-
3.6% in the faeces and 18.9-24.6% remained in the tissues examined
(liver, stomach, muscle, blood, plasma, adipose tissue). The residual
radioactivity was highest in the adipose tissue (9-15%), followed by
muscle (6.5-7.5%) and liver (1.7-2.2%) (De Bethizy et al., 1987).
The disposition of (1-14C)-acrylic acid was also determined in
male Sprague-Dawley rats following oral administration by gavage in
water at 400 mg/kg body weight. Excretion of acrylic acid-derived
radioactivity was determined by collection of urine, faeces and
expired air for 72 h following administration. The predominant route
of excretion was in the expired air with approximately 80% of the
radioactivity exhaled as 14CO2 within 24 h and 83.2% after 72 h.
Elimination of radioactivity as exhaled volatile organic compounds was
negligible (less than 0.5% of the radiolabel). Within 24 h of dose
administration, excretion of radioactivity accounted for 5.0% in the
urine and 8.8% of the radiolabel in faeces. Tissue concentrations of
radioactivity after 72 h were generally low: 0.4% of the total dose in
the liver, 0.39% in muscle and 0.18% in skin (Winter & Sipes, 1993).
A comparative bioavailability and disposition study in male
Fischer-344 rats and male C3H mice after a single administration of
(1-14C)-acrylic acid (40 or 150 mg/kg body weight in water) by gavage
has been conducted. This study confirmed that acrylic acid is rapidly
absorbed and metabolized. In rats and mice about 80-90% of the dose
was exhaled as 14CO2 within 24 h (Black et al., 1995). In rats,
excretion of radiolabel in urine and faeces within 72 h accounted for
< 5% and < 1% of the dose, respectively. Elimination of
radioactivity in rats as exhaled organic volatile compounds was less
than 0.5% of the radiolabel. Similar patterns were observed in male
mice (Black et al., 1995).
6.2.1.2 Inhalation exposure
A tissue distribution study has been conducted in 39 female
Sprague-Dawley rats nose-exposed to (1-11C)-acrylic acid vapour for
1 min (concentration not indicated). Radioactivity was widely
distributed; 90 seconds after exposure 18.3% of the delivered dose
remained in the rats. Approximately 28.0% of this radioactivity was
associated with the snout and 42.9% of the radioactivity was found in
the head; this was considered to be solubilized in the mucous of the
turbinates and the nasopharynx. After 65 min, the activity in the
snout was reduced to 8.1% and approximately 60% of the label was
expired as 11CO2. The elimination of labelled CO2 appeared to be
biphasic, with a half-time of approximately 30.6 min during the
alpha-phase. The amount of radioactivity retained in liver and fat
increased markedly between 1.5 and 65 min post-exposure (Kutzman et
al., 1982).
6.2.1.3 Dermal exposure
In one in vitro experiment, the dermal penetration capacity of
(1-14C)-acrylic acid was tested using excised mouse skin. Skin slices
were treated in a diffusion chamber with 0.01, 0.1, 1 and 4% (w/v)
100 µl/cm2 of acrylic acid dissolved in acetone, water or phosphate
buffer pH 6.5. The results were comparable with the study performed on
excised human skin (section 6.1). Permeability coefficients for mouse
skin were 0.96-1.73 × 10-3 cm/h for water and 1.91-3.1 × 10-4 cm/h
for phosphate buffer. The permeability coefficients and steady-state
absorption rate data indicate that mouse skin is approximately three
times more permeable than human skin to acrylic acid (Corrigan &
Scott, 1988). This difference may not be biologically significant.
In a briefly reported study, male Sprague-Dawley rats were
administered dermally 5 mg 14C-acrylic acid per kg body weight
(D'Souza & Francis, 1988). Phosphate buffer of pH 6 or 7.4 or acetone
was used as a formulating agent. In each case the formulation was
applied to the shaved back of the rats and covered with a glass
chamber. The rate of appearance of 14CO2 measured at 0.5, 1, 2, 4,
8, 16 and 24 h after application was used as a measure of the
absorption rate of acrylic acid. The absorption rate was dependent on
the vehicle and decreased in the following order, acetone > phosphate
buffer of pH 6 > phosphate buffer of pH 7.4. Cumulative absorption
after 24 h was 22% from acetone, approximately 19% from phosphate
buffer of pH 6, and 9% from phosphate buffer of pH 7.4. The results of
the in vivo investigations were comparable to those of the in
vitro studies obtained by the same authors (D'Souza & Francis, 1988).
The disposition of (1-14C)-acrylic acid was determined in male
Sprague-Dawley rats after topical application of 100 µl of a 4% (v/v)
solution of acrylic acid in acetone to an area of 8.4 cm2 of the skin
(501 µg/cm2) using a skin-mounted, charcoal-containing trap covered
with fixed aluminium discs to ensure complete recovery of the label.
Excretion of acrylic-acid-derived radioactivity was determined by
collection of urine, faeces and expired air for 72 h following
administration of acrylic acid. Approximately 73% of the radioactivity
volatilized from the skin and was trapped in the charcoal sorbent.
After 72 h, 6% of radioactivity was detected at the site of
application in the skin or on the skin surface. Approximately 75% of
the absorbed dose, representing about 16% of the applied dose, was
exhaled as 14CO2 within 12 h. Excretion of radioactivity in the
urine accounted for approximately 9% of the applied radioactivity
(approximately 4% of the absorbed dose), the faeces containing only
negligible amounts of radioactivity. After 72 h, less than 0.4% of the
applied dose was retained in tissues other than skin (Winter & Sipes,
1993).
In another study, 1% (v/v) acetone solutions of 14C-acrylic acid
at doses of 10 or 40 mg/kg were applied to the clipped skin of the
shoulder region of male F-344 rats or male C3H/HeN Crl BR mice. A non-
occlusive "frame" device was cemented to the skin surface of animals
to allow for free evaporation of acrylic acid, which was trapped using
on-line volatile organic traps. Since this technique was inefficient,
activated-charcoal-impregnated filter paper sheets were placed
occlusively on the treated skin surface of a second high dose group of
animals to provide for absorption of evaporating acrylic acid (Black
et al., 1995). In rats, the reported 72-h recovery was low and ranged
from 50 to 60% of the applied dose. Evaporation accounted for most of
the applied acrylic acid, but approximately 26 and 19% of the applied
high and low doses were absorbed in rats within 72 h, respectively.
The major route of elimination of absorbed acrylic acid was via
exhalation of 14CO2 and accounted for 69.5 and 77% of the absorbed
low and high doses, respectively. Minimal faecal elimination of
absorbed acrylic-acid-derived radioactivity was reported (< 1%), and
tissues and carcasses contained approximately 2-3% of the absorbed
chemical at 72 h.
In mice, the 72-h recovery ranged from 61.5 to 84.0% of the
applied acrylic acid dose. As in the rat experiments, while most of
the applied acrylic acid was lost to evaporation, absorption accounted
for 11-12% of the applied dose. Exhalation of 14CO2 accounted for
83.5 and 77.7% of the absorbed high and low doses, respectively.
Elimination via other routes was negligible, and less than 1% of the
absorbed dose remained in the tissues and carcasses at 72 h (Black et
al., 1995).
6.2.1.4 Intravenous administration
Single i.v. doses of (1-14C)-labelled acrylic acid (10 mg/kg
body weight in phosphate-buffered saline) were given to male F-344
rats and male C3H/HeNCrlBR mice into the tail veins. In rats 63% of
the 14C-dose was eliminated as 14CO2 after 4 h and 68% after 72 h,
while almost no 14C was recovered as exhaled organic volatiles.
Tissue samples (liver, kidney and fat) and plasma contained 1.9% at 1
h, 0.4% at 8 h, and 0.2% at 72 h of the recovered dose. Overall the
recovery was 72.8 ± 10.8%. In mice, 51% of the radioactivity was
exhaled as 14CO2 over the 72-h collection period, the majority
exhaled in the first 4 h. The volatile radioactive fractions were
about 0.6% of the total dose. Overall, 55.7 ± 6.6% of this intravenous
10 mg/kg dose was recovered in mice (Frantz & Beskitt, 1993).
6.2.2 Metabolism
6.2.2.1 In vitro investigations
Oxidation of (2,3-14C)-acrylic acid was studied by incubating
acrylic acid with hepatic microsomal preparations obtained from male
Sprague-Dawley rats. No metabolites were detected by HPLC and acrylic
acid was recovered unchanged from the incubation mixture (De Bethizy
et al., 1987).
Results of the in vitro metabolism of (1-14C)-acrylic acid
incubated with freshly isolated hepatocytes and liver homogenates of
male F-344 rats or mitochondria isolated from liver homogenates of
male F-344 rats indicate that acrylic acid is rapidly metabolized to
14CO2. Addition of equimolar amounts of propionic acid, 3-hydroxy-
propionic acid or 3-mercaptopropionic acid caused a significant
inhibition of the oxidation of acrylic acid by isolated mitochondria.
A single major metabolite co-eluting with 3-hydroxypropionic acid was
found by HPLC analysis in the mitochondrial incubation mixtures. The
authors suggested that acrylic acid is metabolized in vitro by
mammalian enzymes to CO2 via 3-hydroxypropionate by the non-vitamin-
B12 - dependent pathway for propionate metabolism (Finch & Frederick,
1992).
The oxidation rate of acrylic acid in 13 different tissues
(liver, kidney, forestomach, glandular stomach, small and large
intestine, spleen, brain, heart, lung, skeletal muscle, fat and skin)
of male and female C3H/HeNCrlBR mice was measured by incubating tissue
slices with (1-14C)-acrylic acid and collecting 14CO2. All the
tissues studied oxidized acrylic acid to a certain extent, but
activity in kidney, followed by liver, was much higher than in other
tissues. Oxidation of acrylic acid followed pseudo-Michaelis-Menten
kinetics in the liver, kidney and skin, with a Km for all these
tissues of approximately 0.67 mM. Marked differences were observed in
the Vmax values, 2890 ± 436 nmol/h per g for kidney, 616 ± 62 nmol/h
per g for liver and 47.9 ± 5.8 nmol/h per g for skin. Half-lives in
these tissues were 0.13, 0.867 and 10.2 h, respectively. Lung,
glandular stomach, heart, spleen, fat and large intestine preparations
oxidized acrylic acid at rates from 10 to 40% of the rate determined
in the liver; in the remaining tissues reaction rates were less than
10% of those in the liver. Rates of metabolism in tissues from male
and female mice were similar.3-Hydroxypropionic acid was the only
metabolite detected by HPLC analysis following incubation of tissues
with (1-14C)-acrylic acid. To determine if CO2 was formed from the
C1 carbon, and if acetyl-CoA was derived from carbons 2 and 3 of
acrylic acid, the authors incubated (2,3-14C)-acrylic acid and
(1-14C)-acetate with liver and kidney slices and measured the rate of
14CO2 formation. It was concluded that CO2 originated from C1, but
that acetyl-CoA was derived from carbons 2 and 3 of acrylic acid. Both
substrates were oxidized well by the tissues, thus providing for the
complete metabolism of acrylic acid to CO2. The results demonstrate
that the rate of acrylic acid metabolism varies significantly among
mouse tissues and suggested that the kidneys and liver are major sites
of acrylic acid metabolism (Black et al., 1993).
6.2.2.2 In vivo investigations
After oral administration of (2,3-14C)-acrylic acid (4, 40 or
400 mg/kg body weight in 0.5% methylcellulose) to male Sprague-Dawley
rats, the major portion of the radioactivity (up to 65%) was exhaled
as 14CO2 within 24 h. In urine four metabolites were identified by
HPLC analysis. One of the two major metabolites eluted very near to
the solvent front and did not co-elute with acetic acid pyruvic acid
or lactic acid. The second metabolite co-eluted with 3-hydroxypro-
pionic acid. Traces of two other unidentified residues were also
detected. Radioactivity could not be detected at the retention times
corresponding to that of 2,3-epoxypropionic acid, glyceric acid or
N-acetyl- S-(2-carboxy-2-hydroxyethyl)-cysteine, suggesting that
acrylic acid is not epoxidized to 2,3-epoxypropionic acid in vivo.
It was suggested that acrylic acid was metabolized by the non-vitamin-
B12-dependent pathway for propionic acid metabolism, with degradation
to CO2 being the main route of elimination. Residual radioactivity in
tissues may be due to incorporation of 14C from acrylic acid into
acetyl-CoA (De Bethizy et al., 1987).
Using HPLC and NMR analysis, 3-hydroxypropionic acid, N-acetyl-
S-2-(2-carboxyethyl)-cysteine and N-acetyl- S-(2-carboxyethyl)-
cysteine-S-oxide were identified as urinary metabolites after oral
administration of (2,3-14C)-acrylic acid (400 mg/kg body weight in
water by gavage) to male Sprague-Dawley rats. According to the
authors, the detection of mercapturates may be a consequence of the
high dose used in this study (Winter et al., 1992).
HPLC analysis for acrylic acid and its metabolites in rats
revealed that a metabolite that coeluted with 3-hydroxypropionic acid
was found in the urine, plasma and liver of rats that had received
acrylic acid by gavage. Furthermore, a material that co-eluted with
authentic acrylic acid was detected in the urine and liver, but not in
the plasma, of these rats. Acrylic acid, but not 3-hydroxypropionic
acid, was also detected in the urine of rats after cutaneous
application (Black et al., 1995). In mice, 3-hydroxypropionic acid was
identified in the liver after gavage administration of acrylic acid.
No acrylic acid was detected in the liver of these animals (Black et
al., 1995).
6.2.2.3 Metabolic pathways
Acrylic acid is rapidly metabolized to CO2, a major metabolite
formed via acrylyl-CoA by the non-vitamin-B12-dependent pathway of
mammalian propionate catabolism (Finch & Frederick, 1992; Winter et
al., 1992; Black et al., 1993; Winter & Sipes, 1993). This pathway
occurs in the mitochondrion (Finch & Frederick, 1992) and consist of
reactions analogous to fatty acid ß-oxidation (Schultz, 1991).
ß-oxidation is the major route of propionate catabolism in many
invertebrates and plants (Wegner et al., 1968; Halarnkar & Blomquist,
1989); however the primary pathway of propionate catabolism in mammals
is that involving the vitamin-B12-dependent enzyme, methyl-malonyl-
CoA mutase (Black et al., 1993). A small amount of 3-hydroxypropionic
acid was identified as the major urinary metabolite of acrylic acid
(De Bethizy et al., 1987; Winter et al., 1992). There is no evidence
to suggest that epoxide intermediates are formed during the metabolism
of acrylic acid (De Bethizy et al., 1987). N-acetyl- S-(2-
carboxyethyl) cysteine and N-acetyl- S-(2-carboxyethyl) cysteine-
S-oxide were identified in the urine of rats that had received
400 mg/kg (2,3,-14C)-acrylic acid by gavage (Winter et al., 1992),
suggesting a direct reaction between acrylic acid and reduced
glutathione.
The major route of metabolism for acrylic acid esters has been
shown to involve the rapid cleavage of the ester bond by carboxyl
esterases (see Fig. 1) (Ghanayem et al., 1987; Sanders et al., 1988;
Frederik et al., 1994). Thus exposure to acrylic acid esters may
constitute a significant internal exposure to acrylic acid. A
secondary metabolic pathway involves conjugation of the acrylic acid
ester with glutathione to yield acetyl- S-(2-carboxyethyl) cysteine
alkylesters. (Ghanayem et al., 1987; Sanders et al., 1988). This
intermediate may be further metabolized to N-acetyl- S-(2-
carboxyethyl) cysteine and N-acetyl- S-(2-carboxyethyl)-cysteine-
S-oxide. However, it is currently uncertain what proportion of N-
acetyl- S-(2-carboxyethyl) cysteine, or its oxide, formed from the
metabolism of the acrylic acid esters originates from the reaction of
the intact ester with glutathione and what proportion originates from
the conjugation of the released acrylic acid with glutathione (see Fig
1).
On the basis of available information, proposed metabolic
pathways for acrylic acid are summarized in Fig. 1. The proposed
scheme also includes relationships between metabolism of acrylic acid
and its esters (e.g., ethyl acrylate) and metabolism of propionate via
the major vitamin-B12-dependent pathway.
7. EFFECTS ON EXPERIMENTAL ANIMALS AND IN VITRO TEST SYSTEMS
7.1 Single exposure
The acute toxicity of acrylic acid is difficult to ascertain,
owing to the wide range of LD50 values reported (Table 4). However
most data indicate that the substance is of low to moderate toxicity
by the oral and inhalation routes and of moderate toxicity by the
dermal route. It has been proposed that the wide variation in oral
LD50 values may be due to the different forms in which acrylic acid
has been applied, i.e. undiluted, in aqueous solution at various
concentrations or in neutralized solution (BG Chemie, 1991).
Stomach lesions, necrosis and haemorrhage have been reported
following oral dosing of rats with acrylic acid (Ghanayem et al.,
1985; DeBethizy et al., 1987). The lowest dose at which lesions were
seen was 144 mg/kg.
CrL:CDBR rats were exposed (whole body) to aerosol (mean mass
median diameter of 2.3 µm ± 2.3) concentrations of acrylic acid
ranging from 8775 to 14 145 mg/m3 (2925 to 4715 ppm) for 30 min, 8139
to 12 624 mg/m3 (2713 to 4208 ppm) for 60 min, and 3669 to
10 239 mg/m3 (1223 to 3413 ppm) for 120 min. Additionally, rats were
exposed (whole body) to acrylic acid vapour concentrations ranging from
2784 to 6426 mg/m3 (928 to 2142 ppm) for 60 min. Exposure to acrylic
acid produced treatment-related signs of nasal mucosa, upper airway and
lower airway irritation, ocular irritation, corneal opacities and
dermal toxicity in all experimental groups. Deaths, as a function of
both aerosol concentration and exposure duration, were seen in the
30-, 60- and 120-min aerosol exposures. No deaths resulted from the
vapour exposures. Following the 14-day observation period, necropsies
revealed treatment-related alterations of the lungs, eyes and skin
consistent with that of an irritant. However, comparison of LC values
suggested no difference in toxicity between the aerosol and vapour
(Hagan & Emmons, 1991).
Table 4. The acute toxicity (LD50 and LC50) of acrylic acid for experimental animals
Species Route Parameter Dose Reference
Mouse oral LD50 830 mg/kg Klimkina et al., 1969
Mouse oral LD50 1200 mg/kg Zeller, 1958
Rat oral LD50 193 mg/kg IARC, 1979
Rat oral LD50 340 mg/kg Carpenter et al., 1974
Rat oral LD50 1350 mg/kg Majka et al., 1974
Rat oral LD50 1500 mg/kg Zeller, 1958
Rat oral LD50 2520 mg/kg Fassett, 1963
Rat oral LD50 2100-3200 mg/kg Miller, 1964
Rat oral LD50 2500 mg/kg Verschueren, 1983
Mouse subcutaneous LD50 1590 mg/kg Sittig, 1985
Rabbit percutaneous LD50 295 mg/kg Carpenter et al., 1974
Rabbit percutaneous LD50 640 mg/kg Gelbke & Hofman, 1979
Rabbit percutaneous LD50 750 mg/kg IARC, 1979
Rabbit percutaneous LD50 950 mg/kg Fassett, 1963
Mouse inhalation LC50 (2 h) 5300 mg/m3 RTECS, 1989
Rat inhalation LC50 (30 min) 26 000 mg/m3 Hagan & Emmons, 1991
LC50 (60 min) 11 100 mg/m3
LC50 (120 min) 7500 mg/m3
Table 4. (contd.)
Species Route Parameter Dose Reference
Rat inhalation LC50 (4 h) 3600 mg/m3 Majka et al., 1974
Rat inhalation LC50 (4 h) > 5100 mg/m3 Klimisch & Zeller, 1980
Mouse intraperitoneal LD50 17 mg/kg Lawrence et al., 1972
Mouse intraperitoneal LD50 128 mg/kg RTECS, 1989
Mouse intraperitoneal LD50 140 mg/kg Zeller, 1958
Rat intraperitoneal LD50 24 mg/kg Majka et al., 1974
Rat intraperitoneal LD50 24 mg/kg Singh et al., 1972
In a single inhalation study in rats, no deaths occurred when
six animals were exposed to acrylic acid at a concentration of
12 000 mg/m3 (4000 ppm) for 4 h and observed over 14 days (Union
Carbide Corp., 1977).
A single 4-h exposure of six rats to 6000 mg/m3 (2000 ppm) of
acrylic acid caused no death (Carpenter et al., 1974).
One 5-h exposure to an atmosphere saturated with acrylic acid
(6000 ppm or 17 700 mg/m3) given to four rats (2 male, 2 female)
produced nose and eye irritation, respiratory difficulty and
unresponsiveness in all rats. One rat died. Histopathological
examination showed lung haemorrhage and degenerative changes in the
liver and kidney tubules of all rats (Gage, 1970), but these were
possibly secondary changes in dying animals.
Rats exposed for 1 h to acrylic acid concentrations of 300, 900
or 1500 mg/m3 (100, 300 or 500 ppm) exhibited exposure-dependent
decreases in both respiratory frequency and minute volume (Silver et
al., 1981).
In a sensory irritation study, the single exposure to acrylic
acid vapour estimated for a 50% reduction of the respiratory rate
(RD50) was 1539 mg/m3 (513 ppm) in F344/N rats and 2055 mg/m3
(685 ppm) in B6C3F1 mice. During exposure to 225 mg/m3 (75 ppm) of
acrylic acid vapour for 6 h, a 20-30% decrease in minute volume was
observed in both species (Buckley et al., 1984).
7.2 Irritation and sensitization
7.2.1 Eye irritation
Application of acrylic acid in different concentrations (glacial,
10%, 3% and 1%) to rabbit eyes revealed that it is corrosive in high
concentrations, i.e. glacial and 10%; 1% and 3% solution caused eye
irritancy (Majka et al., 1974). There are also other reports of
undiluted acrylic acid causing eye irritation and corneal damage
(Carpenter et al. 1974; BG Chemie, 1991).
7.2.2 Skin irritation and sensitization
7.2.2.1 Skin irritation
Undiluted acrylic acid is corrosive to rabbit skin (Carpenter et
al., 1974; Majka et al., 1974; BG Chemie, 1991). A study with rabbits
reported that a one-minute exposure to a 50% or 20% aqueous solution
caused, respectively, erythema and oedema or slight erythema (BG
Chemie, 1991). Another study reported a 10% solution to be corrosive
when applied to rabbit skin and that a 0.6-5% solution caused
irritation of various severity (Majka et al., 1974).
The irritant effects of repeated dermal exposure have also been
investigated. A 5% acrylic acid solution in acetone caused skin
irritation in the mouse after daily non-occlusive application for 14
days (DePass et al., 1984). No irritation was seen with a 1% solution.
In another study, groups of three strains of mice received dermal
applications of 0.1 ml acrylic acid in acetone 3 times a week for 13
weeks at concentrations of 0, 1 or 4% (Tegeris et al., 1987, 1988). At
4%, there were signs of significant skin irritation (desquamation,
fissures and eschar), with proliferative, degenerative and
inflammatory changes being detected histologically in the epidermis
and dermis, from weeks 1 to 2. At 1%, minimal proliferative changes,
detected histologically, were the only effects seen. No differences
were found between the response of the three strains of mice.
7.2.2.2 Skin sensitization
Acrylic acid has been tested for contact sensitivity in guinea-
pigs. In one study, a 20% aqueous solution of pure unstabilized
acrylic acid was applied to the skin once a day until definite skin
irritation was seen. When challenged topically 11 days later with a 2%
solution, there was no evidence of skin sensitization up to 24 h post-
challenge (BG Chemie, 1991).
In another study, the highest non-irritating concentration of
acrylic acid (not specified) was applied topically four times in 10
days. At the time of the third application, Freund's adjuvant was
injected intradermally. When challenged two weeks later, none of the
10 guinea-pigs showed evidence of skin sensitization (Rao et al.,
1981).
Three out of six guinea-pigs exposed to acrylic acid, said to be
99% pure, showed a skin sensitization response in a Polak test (Parker
& Turk, 1983). Induction was by dermal injections of a total of 1 mg
acrylic acid, together with adjuvant, followed by topical challenge
with 5% acrylic acid. However, the impurities and inhibitors of the
acrylic acid used were not mentioned in the report.
Acrylic acid was found to be an extreme sensitizer by the guinea
pig maximization test and a weak sensitizer by the Landsteiner Draize
test. The compound used for testing was considered pure, but no
analytical data were provided (Magnusson & Kligman, 1969).
Acrylic acid gave a clearly positive result in the Freunds
Complete Adjuvant test in guinea-pigs (Waegemaekers & van der Walle,
1984). Induction was by three intradermal injections of 1.2% followed
by topical application of 2.2 or 7.2%. The positive response was
believed to be due to the historical impurity, alpha,ß-
diacryloxypropionic acid. This impurity was identified in acrylic acid
from just one of three suppliers. Limited testing of acrylic acid from
the other two suppliers gave negative skin sensitization results. It
should be noted that the impurity is not present in acrylic acid
resulting from current production methods involving distillation.
Commercial acrylic acid also contains a small amount of
polymerization inhibitors, usually hydroquinone monomethyl ether
(methoxyphenol). This is a known skin sensitizer in guinea-pigs (van
der Walle et al., 1982). Other inhibitors used with acrylic acid have
also been reported to have skin-sensitizing properties, namely pheno-
thiazine (Costellati et al., 1990) and diphenyl- p-phenylenediamine
(Magnusson et al., 1968; Kalimo et al., 1989). However, it is unclear
whether the small amount of one of these inhibitors present
(0.02-0.1%) could contribute to the skin-sensitizing properties of
commercial acrylic acid.
7.2.3 Upper respiratory tract irritation
Olfactory cell proliferation, as measured by tritiated thymidine
incorporation, was investigated in male F-344 rats and B6C3F1 mice
exposed to 224 mg/m3 (75 ppm) acrylic acid 6 h daily for 5 days. A
17-fold increase in cell proliferation occurred in mice and a 4-fold
increase in rats (Swenberg et al, 1986). Further information on upper
respiratory tract irritation is given in sections 7.1 and 7.3.2.
7.3 Short-term exposure
Results of key studies on the short-term repeated exposure
effects of acrylic acid are presented in Table 5.
Table 5. Key studies on the noncarcinogenic effects of repeated exposures to acrylic acid
Species, route and dosage LOELa NOELa Observed effects Reference
Rat, Fisher-344 oral, 250 mg/kg bw/day 83 mg/kg bw/day Decreased body weight, De Pass et al.,
drinking-water, 0, 83, reduced water and food 1983
250, 750 mg/kg body consumption, changes in
weight/day for 3 months organ weights
Rat, Wistar, gavage, 0, 150 mg/kg bw/day 50% mortality in both Hellwig et al.,
150, 375 mg/kg bw/day, treatment groups, dose- 1993
5 times/week for 3 dependent irritation in the
months forestomach and
glandular stomach,
purulent rhinitis, tubular
nephroses
Rat, Wistar, oral,
drinking-water, 0, 9, 61,
140, 331 mg/kg body
weight/day for 3 months 331 mg/kg bw/day 140 mg/kg bw/day Reduced water and food Hellwig et al.,
consumption in males 1993
Rat, Wistar, oral, 140 mg/kg bw/day 61 mg/kg bw/day Reduced water and food Hellwig et al.,
drinking-water, 0, 9, 61, consumption in males 1993
140, 331 mg/kg body
weight/day for 12 months
Table 5. (contd.)
Species, route and dosage LOELa NOELa Observed effects Reference
Rat, Wistar, oral, 78 mg/kg bw/day No treatment-related Hellwig et al.,
drinking-water, 0, 8, 27, toxic effects including 1993
78 mg/kg body tumorogenicity
weight/day for 26
(males) or 28 (females)
months
Rat, inhalation, 80, 300 300 ppm 80 ppm Nose irritation, lethargy Gage, 1970
ppm, 6 h/day 5 (900 mg/m3) (240 mg/m3) reduced body weight gain
days/week,
20 exposures
Rat, Fisher-344 225 ppm (675 75 ppm Decrease of adipose Miller et al.,
inhalation, 0, 25, 75, mg/m3) (225 mg/m3) tissue in females, lesions 1979
225 ppm, 6 h/day, of nasal mucosa
5 days/week for 2 weeks
Rat, Fisher 344 75 ppm 25 ppm Lesions of nasal olfactory Miller et al.,
inhalation, 0, 5, 25, (225 mg/m3) (75 mg/m3) epithelium 1981
75 ppm, 6 h/day,
5 days/week for
13 weeks
Rat, F-344, and mouse 75 ppm Olfactory cell proliferation Swenberg et al.,
B6C3F1 inhalation, (225 mg/m3) 17-fold in mice, 4-fold in 1986
75 ppm, 6 h/day, 5 days rats
Table 5. (contd.)
Species, route and dosage LOELa NOELa Observed effects Reference
Mouse, B6C3F1 25 ppm Decrease in body weight Miller et al.,
inhalation, 0, 25, 74, (75 mg/m3) gain, lesions in nasal 1979
223 ppm, 6 h/day mucosa
5 days/week for 2 weeks
Mouse, B6C3F inhalation 5 ppm 5 ppm Atrophy, disorganization, Lomax et al.,
0, 5, 25 ppm for 6 or 22 22 h/day 6 h/day necrosis of the olfactory 1994
h/day and 25 ppm for epithelium of nasal
4.4 h/day for 2 weeks, cavity. Recovery after 6
6 weeks recovery period weeks except for mice
exposed to 25 ppm for
22 h/day where
metaplasia was seen
Mouse, B6C3F1 5 ppm Slight focal lesions of Miller et al.,
inhalation, 0, 5, 25, (15 mg/m3) nasal olfactory 1981
75 ppm, 6 h/day 5 epithelium
days/week for 13 weeks
a LOEL = lowest-observed-effect level; NOEL = no-observed-effect level
7.3.1 Oral
Acrylic acid was administered via oral gavage to ten rats for 20
days with doses increasing by 50% every fourth day (range:
135 mg/kg to 684 mg/kg). Reduction in body weight gain and minor
histopathological changes in the stomach were found at higher doses
(Majka et al., 1974).
In a 3-month study (Hellwig et al., 1993), groups of 10 male and
10 female Wistar rats were gavaged, 5 times per week, with acrylic
acid at doses of 150 or 375 mg/kg body weight. A control group of 10
males and 10 females was gavaged with water. A high mortality rate was
observed in experimental groups; 50% of both males and females in the
low-dose group and 60% (males) and 90% (females) in the high-dose
group died. Cyanosis, dyspnoea and irritation ulceration of
forestomach and glandular stomach, purulent rhinitis and lung
emphysema and alveolar hyperaemia were the main findings reported.
Necrotizing tubular nephroses were seen in the animals that died
during the study. The symptoms and histopathological findings were
substantially the same in both groups, but they were less pronounced
and observed in a smaller number of animals given acrylic acid at
150 mg/kg body weight.
Acrylic acid was given to Wistar rats in drinking-water for
3 months as part of a 12-month study (Hellwig et al., 1993). Further
details are given in section 7.4.
In a subchronic study acrylic acid was incorporated into the
drinking-water of rats (15/sex/group) for 3 months, resulting in doses
of 0,83, 250 and 750 mg/kg per day. At the high and intermediate dose
levels, reduction in body weight gain and changes in organ weights
were observed. These effects coincided with a dose-related reduction
in food and water consumption. At the 83 mg/kg dose, the only effect
was a slight reduction in water consumption. No significant treatment-
related histological effects were seen at any dose level (DePass et
al., 1983).
7.3.2 Inhalation
In a short-term inhalation study (Gage, 1970) no adverse effects
were observed in eight rats (four males and four females) exposed to
240 mg/m3 (80 ppm) acrylic acid vapour, 6 h/day, 5 days/week for 20
exposures. Eight rats (four males and four females) exposed at
900 mg/m3 (300 ppm) showed signs of nasal irritation, lethargy and
reduced body weight gain. Histological and haematological examinations
we