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    Published under the joint sponsorship of
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    and the World Health Organization

    First draft prepared by Dr T. Vermeire,
    National Institute of Public Health and
    Environmental Protection, Bilthoven, The Netherlands

    World Health Orgnization
    Geneva, 1992

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    WHO Library Cataloguing in Publication Data


        (Environmental health criteria ; 127)

        1.Acrolein - adverse effects 2.Acrolein - toxicity
        3.Environmental exposure     4.Environmental pollutants 

        ISBN 92 4 157127 6        (LC Classification: QD 305.A6)
        ISSN 0250-863X

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    1. SUMMARY


         2.1. Identity
         2.2. Physical and chemical properties
         2.3. Conversion factors
         2.4. Analytical methods


         3.1. Natural sources
         3.2. Anthropogenic sources
               3.2.1. Production
               Production levels and processes
               3.2.2. Uses
               3.2.3. Waste disposal
               3.2.4. Other sources


         4.1. Transport and distribution between media
         4.2. Abiotic degradation
               4.2.1. Photolysis
               4.2.2. Photooxidation
               4.2.3. Hydration
         4.3. Biotransformation
               4.3.1. Biodegration
               4.3.2. Bioaccumulation


         5.1. Environmental levels
               5.1.1. Water
               5.1.2. Air
         5.2. General population exposure
               5.2.1. Air
               5.2.2. Food
         5.3. Occupational exposure


         6.1. Absorption and distribution
         6.2. Reaction with body components
               6.2.1. Tracer-binding studies
               6.2.2. Adduct formation
               Interactions with sulfhydryl groups
                In vitro interactions with nucleic
         6.3. Metabolism and excretion


         7.1. Single exposure
               7.1.1. Mortality
               7.1.2. Effects on the respiratory tract
               7.1.3. Effects on skin and eyes
               7.1.4. Systemic effects
               7.1.5. Cytotoxicity  in vitro
         7.2. Short-term exposure
               7.2.1. Continuous inhalation exposure
               7.2.2. Repeated inhalation exposure
               7.2.3. Repeated intraperitoneal exposure
         7.3. Biochemical effects and mechanisms of toxicity
               7.3.1. Protein and non-protein sulfhydryl depletion
               7.3.2. Inhibition of macromolecular synthesis
               7.3.3. Effects on microsomal oxidation
               7.3.4. Other biochemical effects
         7.4. Immunotoxicity and host resistance
         7.5. Reproductive toxicity, embryotoxicity, and teratogenicity
         7.6. Mutagenicity and related end-points
               7.6.1. DNA damage
               7.6.2. Mutation and chromosomal effects
               7.6.3. Cell transformation
         7.7. Carcinogenicity
               7.7.1. Inhalation exposure
               7.7.2. Oral exposure
               7.7.3. Skin exposure
         7.8. Interacting agents


         8.1. Single exposure
               8.1.1. Poisoning incidents
               8.1.2. Controlled experiments
               Vapour exposure
               Dermal exposure
         8.2. Long-term exposure


         9.1. Aquatic organisms
         9.2. Terrestrial organisms
               9.2.1. Birds
               9.2.2. Plants


         10.1. Evaluation of human health risks
               10.1.1. Exposure
               10.1.2. Health effects
         10.2. Evaluation of effects on the environment








    Dr  G. Damgard-Nielsen, National Institution of Occupational Health,
        Copenhagen, Denmark

    Dr  I. Dewhurst, Division of Toxicology and Environmental Health,
        Department of Health, London, United Kingdom

    Dr  R. Drew, Toxicology Information Services, Safety Occupational
        Health and Environmental Protection, ICI Australia, Melbourne,
        Victoria, Australia

    Dr  B. Gilbert, Technology Development Company (CODETEC), Cidade
        Universitaria, Campinas, Brazil ( Rapporteur)

    Dr  K. Hemminki, Institute of Occupational Health, Helsinki ( Chairman)

    Dr  R. Maronpot, Chemical Pathology Branch, Division of Toxicology,
        Research and Testing, National Institute of Environmental Health
        Sciences, Research Triangle Park, North Carolina, USA

    Dr  M. Noweir, Industrial Engineering Department, College of
        Engineering, King Abdul Aziz University, Jeddah, Saudi Arabia

    Dr  M. Wallén, National Chemicals Inspectorate, Solna, Sweden


    Ms  B. Labarthe, International Register of Potentially Toxic
        Chemicals, United Nations Environment Programme, Geneva,

    Dr  T. Ng, Office of Occupational Health, World Health Organization,

    Dr  G. Nordberg, International Agency for Research on Cancer, Lyon,

    Professor F. Valic, IPCS Consultant, World Health Organization,
    Geneva, Switzerland ( Responsible Officer and Secretary)a

    Dr  T. Vermeire, National Institute of Public Health and
        Environmental Protection, Bilthoven, The Netherlands


    a Vice-rector, University of Zagreb, Zagreb, Yugoslavia


         Every effort has been made to present information in the
    criteria documents as accurately as possible without unduly delaying
    their publication.  In the interest of all users of the
    environmental health criteria documents, readers are kindly
    requested to communicate any errors that may have occurred to the
    Manager of the International Programme on Chemical Safety, World
    Health Organization, Geneva, Switzerland, in order that they may be
    included in corrigenda.

                                  *   *   *

         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. 7988400 or


         A WHO Task Group on Environmental Health Criteria for Acrolein
    met in Geneva from 7 to 11 May 1990.  Dr M. Mercier, Manager, IPCS,
    opened the meeting and welcomed the participants on behalf of the
    heads of 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 acrolein.

         The first draft of this monograph was prepared by Dr T.
    Vermeire, National Institute of Public Health and Environmental
    Protection, Bilthoven, Netherlands.  Professor F. Valic was
    responsible for the overall scientific content, and Dr P.G. Jenkins,
    IPCS, for the technical editing.

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


    BOD       biochemical oxygen demand

    COD       chemical oxygen demand

    EEC       European Economic Community

    HPLC      high-performance liquid chromatography

    LOAEL     lowest-observed-adverse-effect level

    NAD       nicotinamide adenine dinucleotide

    NADPH     reduced nicotinamide adenine dinucleotide phosphate

    NIOSH     National Institute for Occupational Safety and Health

    NOAEL     no-observed-adverse-effect level

    1.  SUMMARY

         Acrolein is a volatile highly flammable liquid with a pungent,
    choking, disagreeable odour.  It is a very reactive compound.

         The world production of isolated acrolein was estimated to be
    59 000 tonnes in 1975.  A still larger amount of acrolein is
    produced and consumed as an intermediate in the synthesis of acrylic
    acid and its esters.

         Analytical methods are available for the determination of
    acrolein in various media. The minimum detection limits that have
    been reported are 0.1 µg/m3 air (gas chromatography/mass
    spectrometry), 0.1 µg/litre water (high-pressure liquid
    chromatography), 2.8 µg/litre biological media (fluorimetry),
    590 µg/kg fish (gas chromatography/mass spectrometry), and
    1.4 µg/m3 exhaust gas (high-pressure liquid chromatography).

         Acrolein has been detected in some plant and animal sources
    including foods and beverages.  The substance is primarily used as
    intermediate in chemical synthesis but also as an aquatic biocide.

         Emissions of acrolein may occur at sites of production or use. 
    Important acrolein emissions into the air arise from incomplete
    combustion or pyrolysis of organic materials such as fuels,
    synthetic polymers, food, and tobacco. Acrolein may make up 3-10% of
    total vehicle exhaust aldehydes.  Smoking one cigarette yields
    3-228 µg acrolein.  Acrolein is a product of photochemical oxidation
    of specific organic air pollutants.

         Exposure of the general population will predominantly occur via
    air. Oral exposure may occur via alcoholic beverages or heated

         Average acrolein levels of up to approximately 15 µg/m3 and
    maximum levels of up to 32 µg/m3 have been measured in urban air. 
    Near industries and close to exhaust pipes, levels that are ten to
    one hundred times higher may occur.  Extremely high air levels in
    the mg/m3 range can be found as a result of fires.  In indoor air,
    smoking one cigarette per m3 of room-space in 10-13 min was found
    to lead to acrolein vapour concentrations of 450-840 µg/m3. 
    Workplace levels of over 1000 µg/m3 were reported in situations
    involving the heating of organic materials, e.g., welding or heating
    of organic materials.

         Acrolein is degraded in the atmosphere by reaction with
    hydroxyl radicals. Atmospheric residence times are about one day. 
    In surface water, acrolein dissipates in a few days.  Acrolein has a
    low soil adsorption potential.  Both aerobic and anaerobic
    degradation have been reported, although the toxicity of the
    compound to microorganisms may prevent biodegradation.  Based on the

    physical and chemical properties, bioaccumulation of acrolein would
    not be expected to occur.

         Acrolein is very toxic to aquatic organisms.  Acute EC50 and
    LC50 values for bacteria, algae, crustacea, and fish are between
    0.02 and 2.5 mg/litre, bacteria being the most sensitive species. 
    The 60-day no-observed-adverse-effect level (NOAEL) for fish has
    been determined to be 0.0114 mg/litre. Effective control of aquatic
    plants by acrolein has been achieved at dosages of between 4 and
    26 mg/litre.h.  Adverse effects on crops grown on soil irrigated by
    acrolein-treated water have been observed at concentrations of
    15 mg/litre or more.

         In animals and humans the reactivity of acrolein effectively
    confines the substance to the site of exposure, and pathological
    findings are also limited to these sites. A retention of 80-85%
    acrolein was found in the respiratory tract of dogs exposed to
    400-600 mg/m3.  Acrolein reacts directly with protein and
    non-protein sulfhydryl groups and with primary and secondary amines. 
    It may also be metabolized to mercapturic acids, acrylic acid,
    glycidaldehyde or glyceraldehyde. Evidence for the last three
    metabolites has only been obtained  in vitro.

         Acrolein is a cytotoxic agent.   In vitro cytotoxicity has
    been observed at levels as low as 0.1 mg/litre.  The substance is
    highly toxic to experimental animals and humans following a single
    exposure via different routes.  The vapour is irritating to the eyes
    and respiratory tract. Liquid acrolein is a corrosive substance. 
    The NOAEL for irritant dermatitis from ethanolic acrolein was found
    to be 0.1%.  Experiments with human volunteers, exposed to acrolein
    vapour, show a lowest-observed-adverse-effect level (LOAEL) of
    0.13 mg/m3, at which level eyes may become irritated within 5 min. 
    In addition, respiratory tract effects are evident from 0.7 mg/m3. 
    At higher single exposure levels, degeneration of the respiratory
    epithelium, inflammatory sequelae, and perturbation of respiratory
    function develop.

         The toxicological effects from continuous inhalation exposure
    at concentrations from 0.5 to 4.1 mg/m3 have been studied in rats,
    dogs, guinea-pigs, and monkeys.  Both respiratory tract function and
    histopathological effects were seen when animals were exposed to
    acrolein at levels of 0.5 mg/m3 or more for 90 days.

         The toxicological effects from repeated inhalation exposure to
    acrolein vapour at concentrations ranging from 0.39 mg/m3 to 11.2
    mg/m3 have been studied in a variety of laboratory animals. 
    Exposure durations ranged from 5 days to as long as 52 weeks.  In
    general, body weight gain reduction, decrement of pulmonary
    function, and pathological changes in nose, upper airways, and lungs
    have been documented in most species exposed to concentrations of
    1.6 mg/m3 or more for 8 h/day.  Pathological changes include

    inflammation, metaplasia, and hyperplasia of the respiratory tract.
    Significant mortality has been observed following repeated exposures
    to acrolein vapour at concentrations above 9.07 mg/m3.  In
    experimental animals acrolein has been shown to deplete tissue
    glutathione and in  in vitro studies, to inhibit enzymes by
    reacting with sulfhydryl groups at active sites.  There is limited
    evidence that acrolein can depress pulmonary host defences in mice
    and rats.

         Acrolein can induce teratogenic and embryotoxic effects if
    administered directly into the amnion.  However, the fact that no
    effect was found in rabbits injected intravenously with 3 mg/kg
    suggests that human exposure to acrolein is unlikely to affect the
    developing embryo.

         Acrolein has been shown to interact with nucleic acids
     in vitro and to inhibit their synthesis both  in vitro and
     in vivo.  Without activation it induced gene mutations in bacteria
    and fungi and caused sister chromatid exchanges in mammalian cells. 
    In all cases these effects occurred within a very narrow dose range
    governed by the reactivity, volatility, and cytotoxicity of
    acrolein.  A dominant lethal test in mice was negative.  The
    available data show that acrolein is a weak mutagen to some
    bacteria, fungi, and cultured mammalian cells.

         In hamsters that were exposed for 52 weeks to acrolein vapour
    at a level of 9.2 mg/m3 for 7 h/day and 5 days/week and were
    observed for another 29 weeks, no tumours were found.  When hamsters
    were exposed to acrolein vapour similarly for 52 weeks, and, in
    addition, to intratracheal doses of benzo[a]pyrene weekly or to
    subcutaneous doses of diethylnitrosamine once every three weeks, no
    clear co-carcinogenic action of acrolein was observed. Oral exposure
    of rats to acrolein in drinking-water at doses of between 5 and
    50 mg/kg body weight per day (5 days/week for 104-124 weeks) did not
    induce tumours.  In view of the limited nature of all these tests,
    the data for determining the carcinogenicity of acrolein to
    experimental animals are considered inadequate.  In consequence, an
    evaluation of the carcinogenicity of acrolein to humans is also
    considered impossible.

         The threshold levels of acrolein causing irritation and health
    effects are 0.07 mg/m3 for odour perception, 0.13 mg/m3 for eye
    irritation, 0.3 mg/m3 for nasal irritation and eye blinking, and
    0.7 mg/m3 for decreased respiratory rate.  As the level of
    acrolein rarely exceeds 0.03 mg/m3 in urban air, it is not likely
    to reach annoyance or harmful levels in normal circumstances.

         In view of the high toxicity of acrolein to aquatic organisms,
    the substance presents a risk to aquatic life at or near sites of
    industrial discharges, spills, and biocidal use.


    2.1  Identity

         Chemical formula:      C3H4O

         Chemical structure:


         Relative molecular     56.06

         Common name:           acrolein

         Common synonyms:       acraldehyde, acrylaldehyde (IUPAC name),
                                acrylic aldehyde, propenal, prop-2-enal,

         Common trade           Acquinite, Aqualin, Aqualine, Biocide,
         names:                 Magnicide-H, NSC 8819, Slimicide

         CAS chemical name:     2-propenal

         CAS registry           107-02-8

         RTECS registry         AS 1050000

         Specifications:        commercial acrolein contains 95.5% or
                                more of the compound and, as main
                                impurities, water (up to 3.0% by weight)
                                and other carbonyl compounds (up to 1.5%
                                by weight), mainly propanal and acetone. 
                                Hydroquinone is added as an inhibitor of
                                polymerization (0.1-0.25% by weight)
                                (Hess  et al., 1978).

    2.2  Physical and chemical properties

         Acrolein is a volatile, highly flammable, lacrimatory liquid at
    ordinary temperature and pressure.  Its odour is described as burnt
    sweet, pungent, choking, and disagreeable (Hess  et al., 1978;
    Hawley, 1981).  The compound is highly soluble in water and in
    organic solvents such as ethanol and diethylether. The extreme
    reactivity of acrolein can be attributed to the conjugation of a
    carbonyl group with a vinyl group within its structure.  Reactions
    shown by acrolein include Diels-Alder condensations, dimerization
    and polymerization, additions to the carbon-carbon double bond,

    carbonyl additions, oxidation, and reduction.  In the absence of an
    inhibitor, acrolein is subject to highly exothermic polymerization
    catalysed by light and air at room temperature to an insoluble,
    cross-linked solid.  Highly exothermic polymerization also occurs in
    the presence of traces of acids or strong bases even when an
    inhibitor is present.  Inhibited acrolein undergoes dimerization
    above 150 °C.  Some physical and chemical data on acrolein are
    presented in Table 1.

    Table 1.  Some physical and chemical data on acrolein

    Physical state                       mobile liquid

    Colour                               colourless (pure) or
                                         yellowish (commercial)

    Odour perception threshold           0.07 mg/m3 a

    Odour recognition threshold          0.48 mg/m3 b

    Melting point                        -87 °C

    Boiling point (at 101.3 kPa)         52.7 °C

    Water solubility (at 20 °C)          206 g/litre

    Log  n-octanol-water partition       0.9c

    Relative density (at 20 °C)          0.8427

    Relative vapour density              1.94

    Vapour pressure (at 20 °C)           29.3 kPa (220 mmHg)

    Flash point (open cup)               -18 °C

    Flash point (closed cup)             -26 °C

    Flammability limits                  2.8-31.0% by volume

    a  Sinkuvene (1970) (see Table 12)
    b  Leonardos  et al. (1969) (see Table 12)
    c  Experimentally derived by Veith  et al. (1980)

    2.3  Conversion factors

         At 25 °C and 101.3 kPa (760 mmHg), 1 ppm of acrolein =
    2.29 mg/m3 air and 1 mg of acrolein per m3 air = 0.44 ppm.

    2.4  Analytical methods

         A summary of relevant methods of sampling and analysis is
    presented in Table 2.

         Tejada (1986) presented data showing that the air analysis HPLC
    method employing a 2,4-dinitrophenylhydrazine-coated SP cartridge
    (Kuwata  et al., 1983) is equivalent to that using impingers with
    2,4-dinitrophenylhydrazine in acetonitrile (Lipari & Swarin, 1982). 
    The latter method was also evaluated in several laboratories and was
    found adequate for the evaluation of the working environment (Perez
     et al., 1984).  Nevertheless, the separation of
    2,4-dinitrophenylhydrazine derivatives of acrolein and acetone by
    HPLC can present difficulties (Olson & Swarin, 1985).  A highly
    sensitive electrochemical detection method was found by Jacobs &
    Kissinger (1982) to be suitable and was later improved by Facchini
     et al. (1986).

         A personal sampling device for firemen, which employs molecular
    sieves, was described by Treitman  et al. (1980).  Other sampling
    methods using solid sorbents coated with 2,4-dinitrophenylhydrazine,
    as applied by Kuwata  et al. (1983) for location monitoring, were
    found suitable for personal sampling procedures (Andersson  et al.,
    1981; Rietz, 1985).

         The NIOSH procedure for industrial air monitoring involves
    absorption onto N-hydroxymethylpiperazine-coated XAD-2 resin and gas
    chromatographic analysis of the toluene eluate (US-NIOSH, 1984). 
    This method has been validated by a Shell Development Company
    analytical laboratory and was not revised by NIOSH in 1989.

        Table 2.  Sampling, preparation, and analysis of acrolein


    Medium      Sampling method                  Analytical method      Detection    Sample         Comments                   Reference
                                                                        limit        size

    air         absorption in ethanolic          UV spectrometry        20 µg/m3     0.02 m3        suitable for location      Manita &
                solution of                                                                         monitoring; designed       Goldberg
                thiosemicar-bazide                                                                  for analysis of ambient    (1970)
                and hydrochloric acid                                                               air; interference from
                                                                                                    other alpha, ß-unsaturated

    air         absorption in ethanolic          colorimetry            20 µg/m3     0.05 m3        suitable for location      Cohen &
                solution of                                                                         monitoring; designed       Altshuller
                4-hexylresor-cinol,                                                                 for analysis of ambient    (1961), Katz
                mercuric chloride, and                                                              and industrial air and     (1977), Harke
                trichloroacetic acid                                                                exhaust gas; slight        et al. (1972)
                                                                                                    interference from dienes
                                                                                                    and alpha, ß-unsaturated
                                                                                                    aldehydes; also suitable
                                                                                                    for analysis of smoke

    air         absorption in aqueous            colorimetry            20 µg/m3     0.06 m3        suitable for location      Pfaffli (1982),
                sodium bisulfite;                                                                   monitoring; designed       Katz (1977),
                addition of ethanolic                                                               for analysis of ambient    Ayer & Yeager
                solution of                                                                         and industrial air and     (1982)
                4-hexylresorcinol,                                                                  cigarette smoke
                mercuric chloride, and
                trichloroacetic acid;

    Table 2 (contd).


    Medium      Sampling method                  Analytical method      Detection    Sample         Comments                   Reference
                                                                        limit        size

    air         collection on molecular          fluorimetry            2 µg/m3      0.06 m3        suitable for location      Suzuki & Imai
                sieve 3A and 13X;                                                                   monitoring; designed       (1982)
                desorption by heat;                                                                 for analysis of ambient
                collection in water;                                                                air; interference from
                reaction with aqueous                                                               croton-aldehyde and
                o-aminobiphenyl-sulfuric                                                            methylvinyl ketone
                acid; heating

    air         adsorption on Poropak N;         gas chromatography     < 600        0.003-0.008    suitable for personal      Campbell & Moore
                desorption by heat               with flame ionization  µg/m3        m3             monitoring                 (1979)

    air         adsorption on Tenax GC           gas chromatography     0.1          0.006-0.019    suitable for location      Krost et al.
                desorption by heat;              with mass              µg/m3        m3             and personal               (1982)
                cryofocussing                    spectrometric                       (breakthrough  designed for
                                                 detection                           volume)        analysis of ambient air

    air         cryogradient sampling on         gas chromatography     0.1 µg/m3    0.003 m3       suitable for location      Jonsson & Berg
                siloxane-coated                  with flame                                         monitoring; designed       (1983)
                chromosorb W AW;                 ionization and mass                                for analysis of ambient
                desorption by heat               spectrometric                                      air

    air         absorption into ethanol;         gas chromatography     1 µg/m3      0.003-0.04     suitable for location      Nishikawa et al.
                reaction with aqueous            with electron                       m3             monitoring; designed       (1986)
                methoxyamine                     capture detection                                  for analysis of ambient
                hydrochlo-ride-sodium                                                               air
                acetate; bromination;
                adsorption on SP-cartridge;
                elution by diethyl ether

    Table 2 (contd).


    Medium      Sampling method                  Analytical method      Detection    Sample         Comments                   Reference
                                                                        limit        size

    air         absorption into aqueous          gas chromatography     435          0.01 m3        designed for analysis      Saito et al.
                2,4-DNPH hydrochloride;          with flame             µg/m3                       of exhaust gas             (1983)
                extraction by chloroform;        ionization detection
                                                 and anthracene as
                                                 internal standard

    air         collection in cold trap;         gas chromatography                                 designed for analysis      Rathkamp et al.
                warming trap                                                                        of tobacco smoke           (1973)

    air         direct introduction              gas chromatography     0.1          2 cm3          designed for analysis      Richter &
                                                                        g/m3                        of tobacco smoke           Erfuhrth (1979)

    air         adsorption on                    HPLC with UV           0.5          0.1 m3         suitable for location      Kuwata et al.
                2,4-DNPH-phosphoric acid         detection              µg/m3                       monitoring; designed       (1983)
                coated SP-cartridge;                                                                for analysis of
                elution by acetonitrile                                                             industrial and ambient

    air         absorption into solution         HPLC with UV           11           0.02 m3        suitable for location      Lipari & Swarin
                of 2,4-DNPH-perchloric           detection              µg/m3                       monitoring; designed       (1982)
                acid in acetonitrile;                                                               for analysis of exhaust

    air         absorption into solution         HPLC with              1.4          0.02 m3        suitable for location      Swarin & Lipari
                of 2-diphenylacetyl-1,3-         fluorescence           µg/m3                       monitoring; designed       (1983)
                indandione-1-hydrazone           detection                                          for analysis of exhaust
                and hydrochloric acid in                                                            gas

    Table 2 (contd).


    Medium      Sampling method                  Analytical method      Detection    Sample         Comments                   Reference
                                                                        limit        size

    air         absorption into aqueous          HPLC with              10 µg/       1 cigarette    designed for analysis      Manning et al.
                2,4-DNPH-hydrochloric            UV detection           cigarette                   of cigarette smoke         (1983)
                acid and chloroform                                                                 gas phase

    air         absorption into                  gas chromatography     229          0.05 m3        suitable for               US-NIOSH (1984)
                2-(hydroxymethyl)                with                   µg/m3                       personal monitoring
                piperidine on XAD-2;             nitrogen-specific
                elution by toluene               detector

    water       addition of                      colorimetry            400          0.0025         slight interference        Cohen &
                4-hexyl-resorcinol-mercuric                             µg/litre     litre          from dienes and alpha,     Altshuller (1961)
                chloride solution and                                                               ß-unsaturated aldehydes
                trichloroacetic acid to
                sample in ethanol

    water       reaction with methoxylamine      gas chromatography     0.4                         designed for analysis      Nishikawa et al.
                hydrochloride-sodium             with electron          µg/litre                    of rain water              (1987a)
                acetate; bromination;            capture detection
                adsorption on SP
                cartridge; elution by
                diethyl ether

    water       reaction with 2,4-DNPH;          HPLC with              29                          designed for analysis      Facchini et al.
                with addition of                 electro-chemical       µg/litre                    of fog and rain water      (1986)
                iso-octane                       detection

    Table 2 (contd).


    Medium      Sampling method                  Analytical method      Detection    Sample         Comments                   Reference
                                                                        limit        size

    water       low pressure distillation;       HPLC with UV           < 0.1        1000 ml        designed for analysis      Greenhoff &
                cryofocussing into aqueous       detection              µg/litre                    of beer                    Wheeler (1981)
                2,4-DNPH-hydro-chloric acid;
                extraction by chloroform;
                TLC and magnesia-silica-gel
                column chromatography

    biological  reaction with aqueous            fluorimetry            2.8          2 ml           designed for analysis      Alarcon (1968)
      media     m-aminophenol-hydroxyl-                                 µg/litre                    of biological media
                hydrochloric acid;

    tissue      homogenization; reaction         HPLC with UV                                                                  Boor & Ansari
                with aqueous                     detection                                                                     (1986)
                2,4-DNPH-sulfuric acid;
                extraction by chloroform

    food        ultrasonic homogenization        gas chromatography     590          1000 mg        designed for analysis      Easley et al.
                in cooled water; purging         with mass              µg/kg                       of volatile organic        (1981)
                by helium; trapping on           spectrometric                                      compounds in fish
                Tenax GC-silica-gel-charcoal;    detection
                desorption by heat


    3.1  Natural sources

         Acrolein is reported to occur naturally, e.g., in the essential
    oil extracted from the wood of oak trees (IARC, 1979), in tomatoes
    (Hayase  et al., 1984), and in certain other foods (section

    3.2  Anthropogenic sources

    3.2.1  Production  Production levels and processes

         In 1975, the worldwide production of acrolein was estimated to
    be 59 000 tonnes, although at this time production figures probably
    only related to isolated acrolein (Hess  et al., 1978).  It is
    mainly produced in the USA, Japan, France, and Germany.  In
    addition, acrolein is produced as an unisolated intermediate in the
    synthesis of acrylic acid and its esters.  In 1983, 216 000 to
    242 000 tonnes of acrolein was reported to be used in the USA for
    this purpose, amounting to 91-93% of the total production in that
    country (Beauchamp et al.,1985).  Formerly acrolein was produced by
    vapour phase condensation of acetaldehyde and formaldehyde (Hess
     et al., 1978).  Although this process is now virtually obsolete,
    some production via this pathway has continued in the USSR (IRPTC,
    1984).  Worldwide, most acrolein is now produced by the direct
    catalytic oxidation of propene.  Catalysts containing bismuth,
    molybdenum, and other metal oxides enable a conversion of propene of
    over 90% and have a high selectivity for acrolein.  By-products are
    acrylic acid, acetic acid, acetaldehyde, and carbon oxides (Hess
     et al., 1978; Ohara  et al., 1987). Another catalyst used for
    this process, cuprous oxide, has a lower performance (Hess  et al.,
    1978; IRPTC, 1984).  Emissions

         Closed-systems are used in production facilities, and releases
    of acrolein to the environment are expected to be low, especially
    when the compound is directly converted to acrylic acid and its
    esters.  The compound is emitted via exhaust fumes, process waters
    and waste, and following leakage of equipment.  Production losses in
    the USA in 1978 were estimated to be 35 tonnes or approximately 0.1%
    of the amount of isolated acrolein produced (Beauchamp  et al.,

         The air emission factor of acrolein in the synthesis of
    acrylonitrile in the Netherlands has been reported to be 0.1-0.3 kg
    per tonne of acrylonitrile (DGEP, 1988). Acrolein has also been
    identified in the process streams of plants manufacturing acrylic

    acid (Serth  et al., 1978).  The application of acrolein as a
    biocide brings the chemical directly into the aquatic environment.

    3.2.2  Uses

         The principal use of acrolein is as an intermediate in the
    synthesis of numerous chemicals, in particular acrylic acid and its
    lower alkyl esters and DL-methionine, an essential amino acid used
    as a feed supplement for poultry and cattle. In the USA, in 1983, 91
    to 93% of the total quantity of acrolein produced was converted to
    acrylic acid and its esters, and 5% to methionine (Beauchamp
     et al., 1985). Other derivatives of acrolein are:
    2-hydroxyadipaldehyde, 1,2,6-hexanetriol, lysine, glutaraldehyde,
    tetrahydro-benzaldehyde, pentanediols, 1,4-butanediol,
    tetrahydrofuran, pyridine, 3-picoline, allyl alcohol, glycerol,
    quinoline, homopolymers, and copolymers (Hess  et al., 1978).

         Among the direct uses of acrolein, its application as a biocide
    is the most significant one.  Acrolein at a concentration of
    6-10 mg/litre in water is used as an algicide, molluscicide, and
    herbicide in recirculating process water systems, irrigation
    channels, cooling water towers, and water treatment ponds (Hess
     et al., 1978). About 66 tonnes of acrolein is reported to be used
    annually in Australia to control submersed plants in about 4000 km
    of irrigation channels (Bowmer & Sainty, 1977; Bowmer & Smith,
    1984).  Acrolein protects feed lines for subsurface injection of
    waste water, liquid hydrocarbon fuels and oil wells against the
    growth of microorganisms, and at 0.4-0.6 mg/litre it controls slime
    formation in the paper industry.  The substance can also be used as
    a tissue fixative, warning agent in methyl chloride refrigerants,
    leather tanning agent, and for the immobilization of enzymes via
    polymerization, etherification of food starch, and the production of
    perfumes and colloidal metals (Hess  et al., 1978; IARC, 1985).

    3.2.3  Waste disposal

         Acrolein wastes mainly arise during production and processing
    of the compound and its derivatives.

         Aqueous wastes with low concentrations of acrolein are usually
    neutralized with sodium hydroxide and fed to a sewage treatment
    plant for biological secondary treatment.  Concentrated wastes are
    reprocessed whenever possible or burnt in special waste incinerators
    (IRPTC, 1985).

    3.2.4  Other sources

         Incomplete combustion and thermal degradation (pyrolysis) of
    organic substances such as fuels, tobacco, fats, synthetic and
    natural polymers, and foodstuffs frequently result in the emission
    of aldehydes.  Reported levels are presented in section 5.1.2. 
    Emission rates for several of such sources are presented in Table 3.

         The major sources of aldehydes in ambient air formed by
    incomplete combustion and/or thermal degradation are residential
    wood burning, burning of coal, oil or natural gas in power plants,
    burning of fuels in automobiles, and burning of refuse and
    vegetation (Lipari  et al., 1984).  Formaldehyde is the major
    aldehyde emitted, but acrolein may make up 3 to 10 % of total
    automobile exhaust aldehydes and 1 to 13% of total wood-smoke
    aldehydes (Fracchia  et al., 1967; Oberdorfer, 1971; Lipari
     et al., 1984).  Modern catalytic converters in automobiles almost
    completely remove these aldehydes from exhaust gases.  Acrolein may
    constitute up to 7% of the aldehydes in cigarette smoke (Rickert
     et al., 1980).

         Aldehydes are also formed by photochemical oxidation of
    hydrocarbons in the atmosphere.  Leach  et al. (1964) concluded
    that formaldehyde and acrolein would constitute 50% and 5%,
    respectively, of the total aldehyde present in irradiated diluted
    car exhaust.  Acrolein was considered to be mainly a product of
    oxidation of 1,3-butadiene (Schuck & Renzetti, 1960; Leach  et al.,
    1964), but propene (Graedel  et al., 1976; Takeuchi & Ibusuki,
    1986), 1,3-pentadiene, 2-methyl-1,3-pentadiene (Altshuller &
    Bufalini, 1965), and crotonaldehyde (IRPTC, 1984) have also been
    implicated. The photooxidation of 1,3-butadiene in an irradiated
    smog chamber, also containing nitrogen monoxide and air, gave rise
    to the formation of acrolein (55% yield based on 1,3-buta-diene
    initial concentrations).  The rate of formation of acrolein was the
    same as that of 1,3-butadiene consumption.  (Maldotti  et al.,
    1980).  Cancer chemotherapy patients receiving cyclo-phosphamide are
    exposed to acrolein, which results from the metabolism of this drug.

        Table 3.  Emission rates of aldehydes


    Source                                    Total          Formaldehyde    Acrolein       Unit            Reference

    Residential wood burning                  0.6-2.3        0.089-0.708     0.021-0.132    g/kg            Lipari et al. (1984)
    Power plants - coal                                      0.002                          g/kg            Natusch (1978)
                 - oil                                       0.1                            g/kg
                 - natural gas                               0.2                            g/kg
    Automobiles  - petrol                     0.01-0.08                                     g/km            Lipari et al. (1984)
                                              0.4-2.3        0.2-1.6         0.01-0.16      g/litre         Guicherit & Schulting
                                              8.4-63         4-38            1-2            mg/min          Lies et al. (1986)
                 - diesel                     0.021                                         g/km            Lipari et al. (1984)
                                              1-2            0.5-1.4         0.03-0.20      g/litre         Guicherit & Schulting
                                                             0.0080          0.0002         g/litre         Smythe & Karasek (1973)
                                              44             18              3              mg/min          Lies et al. (1986)
    Vegetation burning                        0.003                                         g/kg            Lipari et al. (1984)
    Cigarette smoking                         82-1203                        3-228          µg/cigarette    see section 5.2.1
    Pyrolysis of flue-cured tobacco                                          42-82          µg/g            Baker et al. (1984)
    Heating in air (at up to 400 °C) of
      - polyethylene                                         up to 75        up to 20       g/kg            Morikawa (1976)
      - polypropylene                                        up to 54        up to  8       g/kg
      - cellulose                                            up to 27        up to  3       g/kg
      - glucose                                              up to 18        up to  1       g/kg
      - wood                                                 up to 15        up to  1       g/kg
    Smouldering cellulosic materials                         0.66-10.02      0.46-1.74      g/kg
    Hot wire cutting (50 cm long at 215 °C)
      of PVC wrapping film                                                   27-151         ng/cut          Boettner & Ball (1980)


    4.1  Transport and distribution between media

         Acrolein is released into the atmosphere during the production
    of the compound itself and its derivatives, in industrial and
    non-industrial processes involving incomplete combustion and/or
    thermal degradation of organic substances, and, indirectly, by
    photochemical oxidation of hydrocarbons in the atmosphere. Emissions
    to water and soil occur during production of the compound itself and
    its derivatives, and through biocidal use, spills, and waste
    disposal (chapter 3).

         Intercompartmental transport of acrolein should be limited in
    view of its high reactivity, as is discussed in sections 4.2. and
    4.3.  Considering the high vapour pressure of acrolein, some
    transfer across the water-air and soil-air boundaries can be
    expected.  In a laboratory experiment Bowmer  et al. (1974)
    explained a difference of 10% between the amount of total aldehydes
    (acrolein and non-volatile degradation products, see section 4.2) in
    an open tank and that in closed bottles by volatilization.  It was
    noted that volatilization may be greatly increased by turbulence.

         Adsorption to soil, often involving probable reaction with soil
    components, may impair the transfer of a compound to air or ground
    water.  The tendency of untreated acrolein to adsorb to soil
    particles can be expressed in terms of Koc, the ratio of the
    amount of chemical adsorbed (per unit weight of organic carbon) to
    the concentration of the chemical in solution at equilibrium.  Based
    on the available empirical relationships derived for estimating
    Koc, a low soil adsorption potential is expected (Lyman  et al.,
    1982).  Experimentally, acrolein showed a limited (30% of a 0.1%
    solution) adsorbability to activated carbon (Giusti  et al., 1974).

    4.2  Abiotic degradation

         Once in the atmosphere, acrolein may photodissociate or react
    with hydroxyl radicals and ozone.  In water, photolysis or hydration
    may occur.  These processes will be discussed in the following

    4.2.1  Photolysis

         Acrolein shows a moderate absorption of light within the solar
    spectrum at 315 nm (with a molar extinction coefficient of 26
    litre/mol per cm) and therefore would be expected to be
    photoreactive (Lyman  et al., 1982).  However, irradiation of an
    acrolein-air mixture by artificial sunlight did not result in any
    detectable photolysis (Maldotti  et al., 1980).  Irradiation of
    acrolein vapour in high vacuum apparatus at 313 nm and 30-200 °C
    resulted in the formation of trace amounts of ethene and carbon
    oxides (Osborne  et al., 1962; Coomber & Pitts, 1969).

    4.2.2  Photooxidation

         Experimentally determined rate constants for the pseudo first
    order reaction between acrolein and hydroxyl radicals in the
    atmosphere are presented in Table 4. Also shown are the atmospheric
    residence times, which can be derived from the rate constants
    assuming a 12-h daytime average hydroxyl radical concentration of
    2 x 10-15 mol/litre (Lyman  et al., 1982). The estimated
    atmospheric residence time of acrolein of approximately 20 h will
    decrease with increasing hydroxyl radical concentrations in more
    polluted atmospheres and increase with the decline in temperature,
    and consequently the rate of reaction, at higher altitudes.  Other
    variations will be caused by seasonal, altitudinal, diurnal, and
    geographical fluctuations in the hydroxyl radical concentration.

         Other potentially significant gas-phase reactions in the
    atmosphere may occur between acrolein and ozone or nitrate radicals. 
    Experimentally determined rate constants and atmospheric residence
    times for these reactions are shown in Table 4.  The atmospheric
    residence times were estimated assuming a 24-h average ozone
    concentration of 1.6 x 10-9 mol/litre (Lyman  et al., 1982) and a
    12-h night-time average nitrate radical concentration of 4.0 x
    10-12 mol/litre (Atkinson  et al., 1987).  It can be concluded
    that the tropospheric removal processes for acrolein are dominated
    by the reaction with hydroxyl radicals. Carbon monoxide,
    formaldehyde, glycoaldehyde, ketene, and peroxypropenyl nitrate have
    been identified as products of the reaction between acrolein and
    hydroxyl radicals (Edney  et al., 1982), and glyoxal was also
    suggested to be one of the reaction products (Edney  et al., 1982,

         As discussed in section 3.2.4, acrolein is also formed by the
    photochemical degradation of hydrocarbons in general and
    1,3-butadiene in particular. When mixtures of acrolein or
    1,3-butadiene with nitrogen monoxide and air were irradiated in a
    smog chamber, the time required for the half-conversion of
    1,3-butadiene to acrolein was always shorter than that required for
    the half conversion of acrolein.  It was concluded that in a real
    atmospheric environment, with continuous emissions of 1,3-butadiene,
    acrolein will be continuously formed (Bignozzi  et al., 1980).

        Table 4.  Rate constants and calculated atmospheric residence times for gas-phase reactions of acrolein.


    Reactant       Temperature      Technique used      Rate constant            Atmospheric       Reference
                      (°C)                              (litre/mol per sec)      residence time

    OH radical         25           relative rate          16   x 109                  17          Maldotti et al. (1980)
                       25           relative rate          11.4 x 109                  24          Kerr & Sheppard (1981)
                       23           absolute rate          20.6 x 109                  13          Edney et al. (1982)
                       26           relative rate          11.4 x 109                  24          Atkinson et al. (1983)
                       23           relative rate          12.3 x 109                  23          Edney et al. (1986a)
    O3                 23           absolute rate          16.9 x 104                1029          Atkinson et al. (1981)
    NO3                25           relative rate          35.5 x 104                 391          Atkinson et al. (1987)

    4.2.3  Hydration

         Acrolein does not contain hydrolysable groups but it does react
    with water in a reversible hydration reaction to 3-hydroxypropanal. 
    The equilibrium constant is pH independent and increases appreciably
    with increasing initial acrolein concentration, presumably because
    of the reversible dimerization of 3-hydroxypropanal (Hall & Stern,
    1950).  In more dilute solutions the equilibrium constant was found
    to approach 12 at 20 °C (Pressman & Lucas, 1942; Hall & Stern,
    1950), indicating that approximately 92% of acrolein is in the
    hydrated form at equilibrium.  This agrees well with the equilibrium
    concentrations found in buffered solutions of acrolein at 21 °C
    (Bowmer & Higgins, 1976).

         The hydration of acrolein is a first order reaction with
    respect to acrolein.  The rate constants are independent of the
    initial acrolein concentrations but increase with increasing acid
    concentrations (Pressman & Lucas, 1942; Hall & Stern, 1950) and also
    when the pH is raised from 5 to 9 (Bowmer & Higgins, 1976).  In
    dilute buffered solutions of acrolein in distilled water the rate
    constant is 0.015 h-1 at 21 °C and pH 7, corresponding to a
    half-life of 46 h.  However, although in laboratory experiments an
    equilibrium is reached with 8% of the original acrolein and 85% of
    total aldehydes still present, these do not persist in river waters
    so that other methods of dissipation must exist (Bowmer  et al.,
    1974; Bowmer & Higgins, 1976; see also section 4.3.1).

         The dissipation of acrolein in field experiments in irrigation
    channels also followed first order kinetics and was faster than
    could be predicted assuming hydration alone.  First order rate
    constants, based on the data thought to be most reliable varied
    between 0.104 and 0.208 h-1 at pH values of 7.1 to 7.5 and
    temperatures of 16 to 24 °C.  From these rate constants, half-lives
    of between 3 and 7 h can be calculated (O'Loughlin & Bowmer, 1975;
    Bowmer & Higgins, 1976; Bowmer & Sainty, 1977).  The latter data
    agree better than the laboratory data with the results of bioassays
    with bacteria and fish, which show that aged acrolein solutions
    become biocidally inactive after approximately 120 to 180 h at a pH
    of 7 (Kissel  et al., 1978).  Apparently processes other than
    hydration also contribute to acrolein dissipation, e.g., catalysis
    other than acid-base catalysis, adsorption, and volatilization
    (Bowmer & Higgins, 1976).

    4.3  Biotransformation

    4.3.1  Biodegradation

         No biological degradation of acrolein was observed in two BOD5
    tests with unacclimated microorganisms (Stack, 1957; Bridie  et al.,
    1979a) or in an anaerobic digestion test with unacclimated
    acetate-enriched cultures (Chou  et al., 1978).  In two of these

    cases this was explained by the toxicity of the test compound to
    microorganisms (Stack, 1957; Chou  et al., 1978).  The BOD5 of
    acrolein in river water containing microorganisms acclimated to
    acrolein over 100 days was found to be 30% of the theoretical oxygen
    demand (Stack, 1957). Applying methane fermentation in a mixed
    reactor with a 20-day retention time, seeded by an acetate-enriched
    culture, a 42% reduction in COD was achieved after 70-90 days of
    acclimation to a final daily feed concentration of 10 g/litre (Chou
     et al., 1978). In a static-culture flask-screening procedure,
    acrolein (at a concentration of 5 or 10 mg/litre medium) was
    completely degraded aerobically within 7 days, as shown by gas
    chromatography and by determination of dissolved organic carbon and
    total organic carbon (Tabak  et al., 1981).

         As discussed in section 4.2.3, acrolein in water is in
    equilibrium with its hydration product. Bowmer & Higgins (1976)
    observed rapid dissipation of this product in irrigation water after
    a lag period of 100 h at acrolein levels below 2-3 mg/litre and
    suggested that this could be due to biodegradation.

    4.3.2  Bioaccumulation

         On the basis of the high water solubility and chemical
    reactivity of acrolein and its low experimentally determined log
     n-octanol-water partition coefficient of 0.9 (Veith  et al.,
    1980), no bioaccumulation would be expected. Following the exposure
    of Bluegill sunfish to 14C-labelled acrolein (13 µg/litre water)
    for 28 days, the half-time for removal of radiolabel taken up by the
    fish was more than 7 days (Barrows et al, 1980).  Although the
    accumulation of acrolein derived radioactively in this study was
    described by the authors as bioaccumulation, it does not represent
    bioaccumulation of acrolein  per se but rather incorporation of the
    radioactive carbon into tissues following the reaction of acrolein
    with protein sulfhydryl groups or metabolism of absorbed acrolein
    and incorporation of label into intermediary metabolites (see
    chapter 6) (Barrows  et al., 1980).


    5.1  Environmental levels

    5.1.1  Water

         Concentrations of acrolein measured in various types of water
    at different locations are summarized in Table 5.

    5.1.2  Air

         Concentrations of acrolein measured in air at different
    locations are summarized in Table 6. Sources of acrolein (see
    chapter 3) are reflected in the levels found.

    5.2  General population exposure

    5.2.1  Air

         The general population can be exposed to acrolein in indoor and
    outdoor air (Table 6).  Levels of up to 32 µg/m3 have been
    measured in outdoor urban air in Japan, Sweden, and the USA.  In
    addition, both smokers and non-smokers are exposed to acrolein as
    the product of pyrolysis of tobacco.  An extensive data base shows a
    delivery of 3-228 µg of acrolein per cigarette to the smoker via the
    gas-phase of mainstream smoke, the amount depending on the type of
    cigarette and smoking conditions (Artho & Koch, 1969; Testa &
    Joigny, 1972; Rathkamp  et al., 1973; Rylander, 1973; Guerin
     et al., 1974; Hoffmann  et al., 1975; Richter & Erfuhrth, 1979;
    Magin, 1980; Rickert  et al., 1980; Manning  et al., 1983; Baker
     et al., 1984). The delivery of total aldehydes was found to be
    82-1255 µg per cigarette (Rickert  et al., 1980), consisting mainly
    of acetaldehyde (Harke  et al., 1972; Rathkamp  et al., 1973).  In
    the mainstream smoke of marijuana cigarettes, 92 µg of acrolein per
    cigarette was found (Hoffmann  et al., 1975).  Non-smokers are
    mainly exposed to the side-stream smoke of tobacco products. 
    Smoking 1 cigarette per m3 of room-space in 10-13 min was found to
    lead to acrolein levels in the gas-phase of side-stream smoke of
    0.84 mg/m3 (Jermini  et al., 1976), 0.59 mg/m3 (derived from
    Harke  et al., 1972), and 0.45 mg/m3 (derived from Hugod  et al.,
    1978).  In one of these experiments it was observed that the
    presence of people in the room reduced the acrolein levels, probably
    by respiratory uptake and condensation onto hair, skin, and
    clothing, (Hugod  et al., 1978).  Evidence has also been presented
    that acrolein is associated with smoke particles.  The fraction of
    acrolein thus associated can be deduced to be 20-75% of the total
    (Hugod  et al., 1978; Ayer & Yeager, 1982).

         The 30-min average acrolein levels measured in air grab-samples
    from four restaurants were between 11 and 23 µg/m3, the maximum
    being 41 µg/m3 (Fischer  et al., 1978).

        Table 5.  Environmental levels of acrolein in water


    Type of water             Location                Detection limit      Levels observeda        Reference
                                                      (µg/litre)           (µg/litre)

    Surface water       USA, irrigation canal,        not reported                                 Bartley & Gangstad (1974)
                        point of application                                       100
                           16 km downstream                                         50
                           32 km downstream                                         35
                           64 km downstream                                         30

    Ground water        USA, water in community       0.1-3.0                       nd             Krill & Sonzogni (1986)
                        and private wells

    Fog water           Italy, Po valley              29                          nd-120           Facchini et al. (1986)

    Rain water          Italy, Po valley              29                            nd             Facchini et al. (1986)

    Rain water          USA, 4 urban locations        not reported                  nd             Grosjean & Wright (1983)
                        USA, 1 urban location                                       50b

    Rain water          Japan, source unknown         0.04                     nd (2 samples)      Nishikawa et al. (1987a)
                                                                            1.5-3.1 (3 samples)

    a   nd = not detected
    b   includes acetone

    Table 6.  Environmental levels of acrolein in air


    Type of site                          Country                Detection limit      Levels observeda       Reference
                                                                 (µg/m3)              (mg/m3)

    Not defined                           The Netherlands                             0.001                  Guicherit & Schulting (1985)

    Urban                                 Los Angeles, USA       7                    nd-0.025               Renzetti & Bryan (1961)
    Urban                                 Los Angeles, USA                            0.002-0.032            Altshuller & McPherson (1963)
                                                                                      (average, 0.016)

    Urban, busy road                      Sweden                 0.1                  0.012                  Jonsson & Berg (1983)

    Urban                                 Japan                  0.5                  nd                     Kuwata et al. (1983)
    Urban                                 Japan                  1                    0.002-0.004            Nishikawa et al. (1986)

    Urban, highway                        USSR                                        nd-0.022               Sinkuvene (1970)
    Residential,                          USSR
      100 m from highway                                                              nd-0.013

    Industrial,                           USSR                                        2.5 (max. of           Plotnikova (1957)
       50 m from petrochemical plant                                                  25/25 samples)
     2000 m from petrochemical plant                                                  0.64 (max. of
                                                                                      21/27 samples)
     1000 m from oil-seed mill            USSR                                        0.1-0.2                Chraiber et al. (1964)
      150 m from oil-seed mill            USSR                                        0.32                   Zorin (1966)

    Near coal coking plant                Czechoslovakia                              0.004-0.009            Masek (1972)
                                                                                      (average, 0.007)

    Table 6 (contd).


    Type of site                          Country                Detection limit      Levels observeda       Reference
                                                                 (µg/m3)              (mg/m3)

    Near pitch coking plant               Czechoslovakia                              0.101-0.37
                                                                                                             (average, 0.223)
    Enamelled wire plants (two),          USSR                                                               Vorob'eva et al. (1982)
      300 m from plants                                                               0.28-0.36
     1000 m from plants                                                               0.14-0.46
     "control area"                                                                   0.001-0.23

    Coffee roasting outlet                USA                    200                  0.59                   Levaggi & Feldstein (1970)
    Incinerator                                                  0.5                  0.5-0.6                Kuwata et al. (1983)

    Fire-fighters' personal monitors      Boston, USA            1150                 > 6.9 (10% of samples) Treitman et al. (1980)
      in over 200 structural fires                               (1-litre sample)     > 0.69 (50% of samples)

    Enclosed space of 8 m3 containing     Japan                                       > 69 (44% of samples)  Morikawa & Yanai (1986)
      burning household combustibles                                                  1370 (max)
      (15% synthetics)

    Enclosed space, pyrolysis of 2-5 g    USA                                                                Potts et al. (1978)
      of polyethylene foam in 147 litres;
      chamber at 380 °C                                                               128-355
      chamber at 340 °C                                                               < 4.6
      chamber at 380 °C, red oak                                                      18.32-412.2
      chamber at 245 °C, wax candles                                                  98.47-249.61
      chamber combustion of 2-5 g of                                                  4.58-52.67
        polyethylene foam

    Cooking area, heating of sunflower    USSR                                        1.1 (max)              Turuk-Pchelina (1960)
      oil at 160-170 °C

    Table 6 (contd).


    Type of site                          Country                Detection limit      Levels observeda       Reference
                                                                 (µg/m3)              (mg/m3)

    Beside exhaust of cars,                                                           0.46-27.71             Cohen & Altshuller (1961),
      unidentified fuel                                                                                      Seizinger & Dimitriades (1972),
                                                                                                             Nishikawa et al. (1986, 1987b)
    Beside exhaust of engines,                                                        0.130-50.6             Sinkuvene (1970),
      gasoline                                                                                               Saito et al. (1983)
      diesel                                                                          0.58-7.2               Sinkuvene (1970),
                                                                                                             Klochkovskii et al. (1981),
                                                                                                             Saito et al. (1983)
    Beside exhaust of cars,                                                           up to 6.1              Hoshika & Takata (1976)
      gasoline                                                                                               Lipari & Swarin (1982)
      diesel                                                                          0.5-2.1                Smythe & Karasek (1973),
                                                                                                             Lipari & Swarin (1982),
                                                                                                             Swarin & Lipari (1983)
      ethanol                                                    11                   nd                     Lipari & Swarin (1982)

    Near jet engine                                                                   nd-0.12                Miyamoto (1986)

    a   max = maximum;  nd = not detected

    5.2.2  Food

         In newly prepared beer, acrolein was found at a level of
    2 µg/litre in one study (Greenhoff & Wheeler, 1981) but was not
    detected in another (Bohmann, 1985). Aging can raise the level to
    5 µg/litre (Greenhoff & Wheeler, 1981).  Higher concentrations were
    reported in another study (Diaz Marot et al, 1983).  However, in
    this case the eight compounds identified after a single
    chromatographic procedure, except for acetaldehyde, did not include
    the principal components identified after three successive
    chromatographic procedures by the earlier authors (Greenhoff &
    Wheeler, 1981) so that superimposition of acrolein and other
    compounds may have occurred.

         The identification of acrolein in wines (Sponholz, 1982)
    followed adjustment of the pH to 8 and distillation procedures that
    might have generated acrolein from a precursor.  Similar
    restrictions may apply to determinations in brandies (Rosenthaler &
    Vegezzi, 1955; Postel & Adam, 1983).  Heated and aged bone grease
    contained an average level of 4.2 mg/kg (Maslowska & Bazylak, 1985).
    Acrolein was further detected as a volatile in "peppery" rums and
    whiskies (Mills  et al., 1954; Lencrerot  et al., 1984), apple
    eau-de-vie (Subden  et al., 1986), in white bread (Mulders & Dhont,
    1972), cooked potatoes (Tajima  et al., 1967), ripe tomatoes
    (Hayase  et al., 1984), vegetable oils (Snyder  et al., 1985), raw
    chicken breast muscle (Grey & Shrimpton, 1966), turkey meat
    (Hrdlicka & Kuca, 1964), sour salted pork (Cantoni  et al., 1969),
    heated beef fat (Umano & Shibamoto, 1987), cooked horse mackerel
    (Shimomura  et al., 1971), and as a product of the thermal
    degradation of amino acids (Alarcon, 1976).

    5.3  Occupational exposure

         Concentrations of acrolein measured at different places of work
    are summarized in Table 7.

        Table 7.  Occupational exposure levels


    Type of site                          Country                Detection limit      Levels observeda       Reference
                                                                 (µg/m3)              (mg/m3)

    Production plant for acrolein         USSR                                        0.1-8.2                Kantemirova (1975, 1977)
      and methyl mercaptopropionic

    Plant manufacturing disposable        USA                    20                   nd-0.07                Schutte (1977)
      microscope drapes, polyethylene
      sheets cut by a hot wire

    Workshop where metals, coated         USSR                                        0.11-0.57 (venting)    Protsenko et al. (1973)
      with anti-corrosion primers                                                     0.73-1.04
      are welded                                                                      (no venting)
    Workshop where metals are gas-cut                                                 0.31-1.04
    Workshop where metals (no primer)                                                 nd
      are welded

    Coal-coking plants                    Czechoslovakia                              0.002-0.55             Masek (1972)
    Pitch-coking plants                                                               0.11-0.493

    Rubber vulcanization plant            USSR                                        0.44-1.5               Volkova & Bagdinov (1969)

    Expresser and forepress shops         USSR                                        2-10b                  Chraiber et al. (1964)
      in oil seed mills

    Plant producing thermoplastics        Finland                20                   nd                     Pfaffli (1982)

    Engine workshops, welding             Denmark                15                   0.031-0.605c           Rietz (1985)

    a   nd = not detected                                                        c   3 out of 13 samples
    b   It should be noted that these levels exceed normal tolerance.


    6.1  Absorption and distribution

         The reactivity of acrolein towards free thiol groups (section
    6.3) effectively reduces the bioavailability of the substance. 
    Controlled experiments on systemic absorption and kinetics have not
    been conducted, but there are indications that acrolein is not
    highly absorbed into the system since toxicological findings are
    restricted to the site of exposure (see chapters 8 & 9).  The fact
    that McNulty  et al. (1984) saw no reduction in liver glutathione
    following inhalation exposure also suggests that inhaled acrolein
    does not reach the liver to any great extent (section 7.3.1).

         Experiments with mongrel dogs showed a high retention of
    inhaled acrolein vapour in the respiratory tract.  The inhaled
    vapour concentrations were measured to be between 400 and
    600 mg/m3.  Retention was calculated by subtracting the amount
    recovered in exhaled air from the amount inhaled.  The total tract
    retention at different ventilation rates was 80 to 85%. Upper tract
    retention, measured after severing the trachea just above the
    bifurcation, was 72 to 85% and was also independent of the
    ventilation rate.  Lower-tract retention, measured after tracheal
    cannulation, was 64 to 71% and slightly decreased as ventilation
    rate increased (Egle, 1972).  Evidence for systemic absorption of
    acrolein from the gastrointestinal tract was reported by Draminski
     et al. (1983), who identified a low level of acrolein-derived
    conjugates in the urine of rats after the ingestion of a single dose
    of 10 mg/kg body weight.  This dose killed 50% of the animals in
    this study.

    6.2  Reaction with body components

    6.2.1  Tracer-binding studies

         The  in vitro binding of 14C-labelled acrolein to protein
    has been investigated using rat liver microsomes.  Acrolein was
    found to bind to microsomal protein in the absence of NADPH or in
    the presence of both NADPH and a mixed-function oxidase inhibitor. 
    Incubation following the addition of free sulfhydryl-containing
    compounds reduced binding by 70-90%, while the addition of lysine
    reduced binding by 12%.  Using gel electrophoresis-fluorography it
    was shown that acrolein, incubated with a reconstituted cytochrome
    P-450 system, migrated mostly with cytochrome P-450.  It was
    concluded that acrolein is capable of alkylating free sulfhydryl
    groups in cytochrome P-450 (Marinello  et al., 1984).

         When rats received tritium-labelled acrolein intraperitoneally
    24 h after partial hepatectomy, the percentages of total liver
    radioactivity recovered in the acid-soluble fraction, lipids,
    proteins, RNA, and DNA were approximately 94, 3.5, 1.2, 0.6, and
    0.4%, respectively, during the first 5 h after exposure.
    Distribution of label was stable for at least 24 h.  Acrolein was
    bound to DNA at a rate of 1 molecule per 40 000 nucleotides.

         A similar DNA-binding rate was observed for the green alga
     Dunaliella bioculata at a 10 times higher acrolein concentration
    (Munsch  et al., 1974a). In  in vitro studies, labelled acrolein
    was found to bind to native calf thymus DNA and other DNA polymerase
    templates at rates of 0.5-1 molecule per 1000 nucleotides (Munsch
     et al., 1974b).  In a follow-up experiment with  Dunaliella
     bioculata, quantitative autoradiography and electron microscopy
    showed that the preferential area of cellular fixation for acrolein
    was the nucleus.  This fixation was stable for at least 2 days,
    while that in the plastid and cytoplasm decreased initially (Marano
    & Demèstere, 1976).  As no adducts were identified in these studies,
    these data were considered unsuitable for evaluation.

    6.2.2  Adduct formation

         The findings of the tracer-binding studies (section 6.2.1) are
    not surprising considering the reactivity of acrolein, which makes
    the molecule a likely candidate for interactions with protein and
    non-protein sulfhydryl groups and with primary and secondary amine
    groups such as occur in proteins and nucleic acids.  These reactions
    are most likely to be initiated by nucleophilic Michael addition to
    the double bond (Beauchamp  et al., 1985; Shapiro  et al., 1986). 
    Beauchamp  et al. (1985) discussed extensively the interactions
    with protein sulfhydryl groups and primary and secondary amine
    groups.  Interactions with sulfhydryl groups

         The non-enzymatic reaction between equimolar amounts of
    acrolein and glutathione, cysteine or acetylcysteine in a buffered
    aqueous solution proceeds rapidly to near-completion, forming stable
    adducts (Esterbauer  et al., 1975; Alarcon, 1976). 
    Acrolein-acetylcysteine and acrolein-cysteine adducts yield on
    reduction  S-(3-hydroxypropyl)mercapturic acid and
     S-(3-hydroxypropyl)-cysteine, respectively (Alarcon, 1976).  The
    reaction between glutathione and acrolein may be catalysed by
    glutathione  S-transferase, as was shown for acrolein-diethylacetal
    and crotonaldehyde (Boyland & Chasseaud, 1967). Biochemical and
    toxicological investigations provide more evidence for the
    interaction, either enzymatic or non-enzymatic, between acrolein and
    free sulfhydryl groups.  In summary, it has been observed that:

         *    acrolein exposure of whole organisms or tissue fractions
              results in glutathione depletion (section 7.3.1);
         *    co-exposure of organisms to acrolein and free
              sulfhydryl-containing compounds protects against the
              biological effects of acrolein (sections 7.3.3, 7.3.4, and
         *    acrolein can inhibit enzymes containing free sulfhydryl
              groups on their active site (section 7.3);
         *    glutathione conjugates appear in the urine of
              acrolein-dosed rats (section 6.3).  In vitro interactions with nucleic acids

         Non-catalytic reactions occur between acrolein and cytidine
    monophosphate (Descroix, 1972), deoxyguanosine (Hemminki  et al.,
    1980), and deoxyadenosine (Lutz  et al., 1982).  Chung  et al.
    (1984) have identified the nucleotides resulting from the reaction
    between acrolein and deoxyguanosine or calf thymus DNA (at 37 °C and
    pH 7) in phosphate buffer.  The adducts identified were the 6- and
    8-hydroxy derivatives of cyclic 1,N2-propano-deoxyguanosine. These
    adducts were shown to be formed in a dose-dependent fashion in
    Salmonella typhimurium TA100 and TA104 following exposure to
    acrolein and identification of the DNA adducts by an immunoassay
    (Foiles  et al., 1989; see also section 7.6.2).  Shapiro  et al.
    (1986) reported that acrolein reacts with cytosine and adenosine
    derivatives (at 25 °C and pH 4.2), yielding cyclic 3,N4 adducts of
    cytosine derivatives and 1,N6 adducts of adenosine derivatives. 
    The reaction between guanosine and acrolein yields the cyclic 1,N2
    adduct (at 55 °C and pH 4).

         The demonstration that acrolein can cause or enhance the
    formation of complexes between DNA strands (DNA-DNA crosslinking)
    and between DNA and cellular proteins (DNA-protein crosslinking) is
    indirect evidence that acrolein interacts with nucleic acids. This
    subject is discussed further in section 7.6.1. However, no studies
    have demonstrated unequivocally the interaction of acrolein with DNA
    following  in vivo administration to animals.

    6.3  Metabolism and excretion

         Acrolein is expected to be eliminated from the body via
    glutathione conjugation (section  Draminski  et al.
    (1983) administered acrolein in corn oil orally to Wistar rats at a
    dose of 10 mg/kg body weight. The urinary metabolites identified by
    gas chromatography with mass spectrometric detection were
     S-carboxylethyl-mercapturic acid and its methyl ester, the latter
    possibly being the result of methylation of the urine samples prior
    to gas chromatography.  In expired air a volatile compound was
    detected by gas chromatography, which was not identified; it was
    reported that its retention time did not correspond to that of
    methyl acrylate, acrolein or allyl alcohol.  The reduced form of

     S-carboxylethyl-mercapturic acid, i.e. S-hydroxypropyl-mercapturic
    acid, was identified by paper and gas chromatography as the sole
    metabolite in the urine of CFE rats injected subcutaneously with a
    1% solution of acrolein in arachis oil at a dose of approximately
    20 mg/kg body weight (Kaye, 1973).  This metabolite was collected
    within 24 h and accounted for 10.5% of the total dose (uncorrected
    for a recovery of 58%).  These data indicate that conjugation with
    glutathione may dominate the metabolism of acrolein.

         Data obtained  in vitro show that acrolein can also be a
    substrate of liver aldehyde dehydrogenase (EC and lung or
    liver microsomal epoxidase (EC (Patel  et al., 1980). 
    Acrolein, at concentrations of approximately 200 mg/litre medium,
    was oxidized to acrylic acid by rat liver S9 supernatant, cytosol,
    and microsomes, but not by lung fractions, in the presence of NAD+
    or NADP+. The reaction proceeded faster with NAD+ as cofactor
    than with NADP+ and was completely inhibited by disulfiram (Patel
     et al., 1980).  Rikans (1987) studied the kinetics of this
    reaction: mitochondrial and cytosolic rat liver fractions each
    contained two aldehyde dehydrogenase activities with Km values of
    22-39 mg/litre and 0.8-1.4 mg/litre.  Microsomes contained a high
    Km activity. Incubation of rat liver or lung microsomes in the
    presence of acrolein and NADPH yielded glycidaldehyde and its
    hydration product glyceraldehyde, showing involvement of microsomal
    cytochrome P-450-dependent epoxidase (Patel  et al., 1980). 
    Postulated pathways of acrolein metabolism are summarized in
    Figure 1.

         In a human study, the intravenous injection of 1g
    cyclophosphamide resulted in the excretion of 1.5% acrolein
    mercapturic acid adduct in the urine (Alarcon, 1976).

         As for the fate of the primary metabolites of acrolein, it has
    been proposed that acrylic acid is methylated and subsequently
    conjugated to yield  S-carboxyl-ethylmercapturic acid, which is a
    known metabolite of methyl acrylate (Draminski  et al., 1983). 
    However, methyl acrylate has never been reported as a metabolite of
    either acrolein or acrylic acid.  It seems more likely that acrylic
    acid is incorporated into normal cellular metabolism via the
    propionate degradative pathway (Kutzman  et al., 1982; Debethizy
     et al., 1987).  Glycidaldehyde has been shown to be a substrate
    for lung and liver cytosolic glutathione  S-transferase (EC and can also be hydrated to glyceraldehyde (Patel  et al.,
    1980). Glyceraldehyde can be metabolized via the glycolytic

    FIGURE 1


    7.1  Single exposure

    7.1.1  Mortality

         The available acute mortality data are summarized in Table 8. 
    Most tests for the determination of the acute toxicity of acrolein
    do not comply with present standards.  Nevertheless, retesting is
    not justified for ethical reasons and in view of the overt high
    toxicity of acrolein following inhalation or oral exposure (Hodge &
    Sterner, 1943).

         In addition to the data in Table 8, an oral LD95 of
    11.2 mg/kg body weight for Charles River rats, observed for 24 h,
    has been reported (Sprince  et al., 1979).  Draminski  et al.
    (1983) reported the deaths of 5/10 rats given 10 mg/kg body weight
    in corn oil by gavage.

    7.1.2  Effects on the respiratory tract

         In vapour exposure tests, the effects observed in experimental
    animals have almost exclusively been local effects on the
    respiratory tract and eyes.

         In the LC50 studies, effects on the respiratory tract were
    clinically observed as nasal irritation and respiratory distress in
    rats (Skog, 1950; Potts  et al., 1978; Crane  et al., 1986),
    hamsters (Kruysse, 1971), mice, guinea-pigs, and rabbits (Salem &
    Cullumbine, 1960) at exposure levels of between 25 mg/m3 for 4 h
    and 95 150 mg/m3 for 3 min.  Rats exposed for 10 min to
    concentrations of 750 or 1000 mg/m3 suffered asphyxiation
    (Catilina  et al., 1966).

         Histopathological investigations in experiments with
    vapour-exposed rats (Skog, 1950; Catilina  et al., 1966; Potts
     et al., 1978; Ballantyne  et al., 1989), hamsters (Kilburn &
    McKenzie, 1978), guinea-pigs (Dahlgren  et al., 1972; Jousserandot
     et al, 1981), and rabbits (Beeley  et al., 1986) revealed varying
    degrees of degeneration of the respiratory epithelium consisting of
    deciliation (see also  in vitro work on cytotoxicity discussed in
    7.1.5), exfoliation, necrosis, mucus secretion, and vacuolization. 
    Also observed were acute inflammatory changes consisting of
    infiltration of white blood cells into the mucosa, hyperaemia, 
    haemorrhages, and intercellular oedema.  Proliferative changes of
    the respiratory epithelium, in the form of early stratification and
    hyperplasia, were observed in hamsters 96 h after exposure to
    13.7 mg/m3 for 4 h (Kilburn & McKenzie, 1978).

        Table 8.  Acute mortality caused by acrolein


    Species/strain             Sex             Route of exposure       Observation      LD (mg/kg bw)            Reference
                                                                       period (days)    or LC50 (mg/m3)a

    Rat (Wistar)               male            inhalation (10 min)            8             750                  Catilina et al. (1966)b

    Rat (Wistar)               not reported    oral                          14             46 (39-56)           Smyth et al. (1951)g

    Rat (unspecified           not             inhalation (30 min)           21             300                  Skog (1950)b,c
    strain)                    reported

    Rat (Sprague-Dawley)       male            inhalation (30 min)           14             95-217               Potts et al. (1978)d

    Rat (Sprague-Dawley)       male and        inhalation (1 h)              14             65 (60-68)           Ballantyne et al. (1989)
                               female          inhalation (4 h)              14             20.8 (17.5-24.8)

    Rat (Sherman)              male and        inhalation (4 h)              14             18                   Carpenter et al. (1949)b,e

    Hamster (Syrian golden)    male and        inhalation (4 h)              14             58 (54-62)           Kruysse (1971)

    Table 8 (contd)


    Species/strain             Sex             Route of exposure       Observation      LD (mg/kg bw)            Reference
                                                                       period (days)    or LC50 (mg/m3)a

    Mouse (unspecified         male            inhalation (6 h)               1             151                  Philippin et al. (1970)f

    Mouse (NMRI)               not reported    intraperitoneal                6             7                    Warholm et al. (1984)g

    a  Where available, 95% confidence limits are given in parentheses.
    b  Determination of acrolein levels was not reported.
    c  No mortality at 100 mg/m3, 100% mortality at 700 mg/m3.
    d  Approximate value:  no mortality at 33 mg/m3, 1/7 and 7/7 died at 95 and 217 mg/m3, respectively.
    e  Approximate value:  2-4/6 died.
    f  No mortality at 71 mg/m3, 100% mortality at 273 mg/m3.
    g  The vehicle was water.

         Functional changes in the respiratory system following acrolein
    vapour exposure have been investigated in guinea-pigs and mice. A
    rapidly reversible increase in respiratory rate was observed in
    intact guinea-pigs during exposure to 39 mg/m3 for 60 min (Davis
     et al., 1967) and to 0.8 mg/m3 or more for 2 h (Murphy  et al.,
    1963) followed by a decrease in respiratory rate and an increase in
    tidal volume.  No changes in pulmonary compliance were reported. 
    Davis  et al. (1967) did not observe these effects in
    tracheotomized animals and concluded that they were caused by reflex
    stimulation of upper airway receptors and not by
    bronchoconstriction. Murphy  et al. (1963), observing that
    anticholinergic bronchodilators, aminophylline and isoproterenol,
    but not antihistaminics, reduced the acrolein-induced increase in
    respiratory resistance, concluded that acrolein caused
    bronchoconstriction mediated through reflex cholinergic stimulation. 
    In another experiment, an increase in respiratory resistance was
    also observed in anaesthetized, tracheotomized guinea-pigs with
    transected medulla during exposure to 43 mg/m3 for up to 5 min
    (Guillerm  et al., 1967b). The effect was not reversed by atropine.
    It was concluded by the authors that acrolein did not cause
    bronchoconstriction via reflex stimulation, but probably via
    histamine release. When anaesthetized mice were exposed to 300 or
    600 mg/m3 for 5 min via a tracheal cannula, respiratory
    resistance, respiratory rate, and tidal volume decreased and
    pulmonary compliance increased at an unspecified time after exposure
    (Watanabe & Aviado, 1974).

         The concentration that produces a 50% decrease in respiratory
    rate (RD50) as a result of reflex stimulation of trigeminal nerve
    endings in the nasal mucosa (sensory irritation) has been used as an
    index of upper respiratory tract irritation.  This effect reduces
    the penetration of noxious chemicals into the lower respiratory
    tract.  The rate of respiration was measured in a body
    plethysmograph, only the animals' heads being exposed to the
    acrolein vapour.  Depending on the strain, RD50 values for mice
    ranged from 2.4 to 6.6 mg/m3 (Kane & Alarie, 1977; Nielsen
     et al., 1984; Steinhagen & Barrow, 1984). In rats a RD50 of
    13.7 mg/m3 was found (Babiuk  et al., 1985).

    7.1.3  Effects on skin and eyes

         Animal skin irritation tests have not been performed and skin
    irritation has not been mentioned as an effect in the acute
    inhalation tests reported.

         One special  in vivo eye irritation test involved
    vapour-exposed and control rabbits.  At analysed concentrations of
    acrolein (method not specified)  between 4.3 and 5.9 mg/m3,
    maintained over 4 h, slight chemosis was observed but no iritis
    (Mettier  et al., 1960).  Eye irritation was observed clinically in

    rodents in several acute inhalation tests, but was not graded (Skog,
    1950; Salem & Cullumbine, 1960; Kruysse, 1971; Potts  et al.,

    7.1.4  Systemic effects

         With respect to systemic effects, most studies have been
    performed at concentrations far above the lethal dose.  When rats
    were exposed to concentrations of acrolein between 1214 and
    95 150 mg/m3 during various periods of time, incapacitation,
    indicated by the inability to walk in a rotating cage, and
    convulsions were observed after 2.8 min at the highest concentration
    and after 27 to 34 min at the lowest concentration.  These effects
    were followed by death after several minutes.  Cyanosis of the
    extremities and agitation were observed at levels of 22 900 mg/m3
    or more (Crane  et al., 1986).

         The effects of acrolein on the cardiovascular system were
    investigated by Egle & Hudgins (1974).  Rats anaesthetized by sodium
    pentobarbital and exposed only via the mouth and nose to
    concentrations between 10 and 5000 mg/m3 for 1 min showed an
    increase in blood pressure at all exposure levels.  The heart rate
    was increased at concentrations from 50 mg/m3 to 500 mg/m3 but
    decreased at 2500 and 5000 mg/m3.  Intravenous experiments
    suggested that increased blood pressor responses resulted from the
    release of catecholamines from sympathetic nerve endings and from
    the adrenal medulla and that the decreased heart rate effect was
    mediated by the vagus nerve (Egle & Hudgins, 1974).

         In an acute oral test with rats exposed at 11.2 mg/kg body
    weight, decreased reflexes, body sag, poor body tone, lethargy,
    stupor, and tremors were observed, as well as respiratory distress
    (Sprince  et al., 1979).

         Because acrolein was shown to induce acute cytotoxicity of the
    rat urinary bladder mucosa when instilled directly into the bladder
    lumen (Chaviano  et al., 1985), this end-point was investigated
     in vivo.  Two days after a single oral or intraperitoneal dose of
    25 mg/kg body weight to ten rats per group, focal simple hyperplasia
    of the urinary bladder was detected in the three surviving rats
    dosed intraperitoneally.  None of the orally exposed rats showed
    this effect, but all exhibited severe erosive haemorrhagic
    gastritis.  Both orally and intraperitoneally exposed rats showed
    eosinophilic degeneration of hepatocytes. No abnormalities were
    observed in sections of lungs, kidneys, and spleen. Acrolein was
    also administered intraperitoneally at single doses of 0.5, 1, 2, 4,
    or 6 mg/kg body weight.  Proliferation of the bladder mucosa was
    evaluated autoradiographically by measuring [3H-methyl]thymidine
    incorporation in exposed versus control rats 5 days after the
    intraperitoneal injection of acrolein and was found to be increased
    nearly two-fold at the highest dose.  Body weight gain was decreased

    at the two highest doses.  Histopathological evaluation of the liver
    and urinary bladder did not reveal abnormalities (Sakata  et al.,

    7.1.5  Cytotoxicity in vitro

         As shown in Table 9, mammalian cell viability is affected by
    acrolein  in vitro at nominal concentrations of 0.1 mg/litre or
    more (not corrected for interaction with culture medium components
    or volatilization).  The concentration at which formaldehyde
    exhibited a similar degree of cytotoxicity was about 6 to 100 times
    higher (Holmberg & Malmfors, 1974; Pilotti  et al., 1975; Koerker
     et al., 1976; Krokan  et al., 1985).

         Acrolein is a known inhibitor of respiratory tract ciliary
    movement  in vitro.  After a 20-min exposure to an acrolein
    concentration of 34-46 mg/m3, the ciliary beating frequency of
    excised sheep trachea decreased by 30% (Guillerm  et al., 1967a). 
    Exposure to 13 mg/m3 for 1 h is the greatest exposure that does
    not stop ciliary activity in excised rabbit trachea (Dalhamn &
    Rosengren, 1971).  The no-observed-effect-level for longer exposure
    periods would be expected to be lower than 13 mg/m3.  Other
     in vitro investigations into the inhibition of ciliary movement by
    acrolein were reviewed by Izard & Libermann (1978).

    7.2  Short-term exposure

    7.2.1  Continuous inhalation exposure

         In two subchronic inhalation studies with rats, changes in
    weight gain, longevity, behaviour, and several physiological
    parameters were reported (Gusev  et al., 1966; Sinkuvene, 1970). 
    Unfortunately, the reports did not give sufficient details on the
    exposure conditions and protocols and the studies are thus of
    limited value in evaluating the toxicological properties of

        Table 9.   In vitro cytotoxicity of acrolein


    Cell type                              Exposure      Effect                          Concentration       Reference
                                           period (h)                                    (mg/litre medium)

    Rat cardiac fibroblasts/myocytes          4          increased lactate                                   Toraason et al. (1989)
                                                         dehydrogenase release               > 2.8

    Rat cardiac myocytes                      2          abolished myocine beat              > 2.8

                                              4          decreased ATP levels                > 0.56

    Mouse Ehrlich Landschutz                  5          92% survivala                         1             Holmberg & Malmfors (1974)

    Diploid ascites tumour cells              5          53% survivala                         5

    Mouse B P8 ascites sarcoma cells         48          20% growth rate inhibition            0.6           Pilotti et al. (1975)
                                             48          94% growth rate inhibition            5.6

    Mouse C1300 neuroblastoma cells          24          50% survivala                         1.7           Koerker et al. (1976)

    Mouse L 1210 leukaemia cells              1          70-80% survivala                      1.1           Wrabetz et al. (1980)

                                              1          < 15% survivala                       2.8

    Chinese hamster ovary cells               5          100% mitotis inhibition               0.6           Au et al. (1980)

    Adult human bronchial                     1          92% colony-forming efficiency         0.06          Krokan et al. (1985)
      fibro-blasts                            1          45% colony-forming efficiency         0.2

    Table 9 (contd).


    Cell type                              Exposure      Effect                          Concentration       Reference
                                           period (h)                                    (mg/litre medium)

    Adult human lymphocytes                  48          decreased replicative index           0.6           Wilmer et al. (1986)
                                             48          100% mitosis inhibition               2.2

    Human K562 chromic myeloid                1          marked reduction in                 > 0.3           Crook et al. (1986a,b)
      leukaemia cells                                    colony-forming ability
    Human bronchial epithelial cells          1          20% colony-forming efficiency         0.06          Grafström et al. (1988)

                                              1          50% colony-forming efficiency         0.06-0.17
                                              1          50% survivala                         0.34

                                              3          clonal growth rate inhibition       > 0.17

                                              3          increase in cross-linkage
                                                         envelope formation                  > 0.06

                                              3          decreased plasminogen
                                                         activator activity                  > 0.56

    Human fibroblasts                         5          63% cell count reduction            < 0.017         Curren et al. (1988)

    DNA-repair deficient human
      fibroblasts                             5          63% cell count reduction              0.045

    a  measured as dye exclusion

         Groups of 7 or 8 Sprague-Dawley rats of both sexes, 7 or 8
    Princeton or Hartley-derived guinea-pigs of both sexes, 2 male
    pure-bred Beagle dogs, and 9 male squirrel-monkeys were exposed to a
    vapourized acrolein-ethanol-water mixture for 90 days (Lyon  et al.,
    1970).  The measured acrolein concentrations were 0, 0.5 (two groups
    for each species), 2.3, and 4.1 mg/m3 and the ethanol
    concentrations were below 18.7 mg/m3. Pathological investigations
    did not include weighing of tissues and organs or examination of the
    tracheas at the lowest exposure level.  There was no
    treatment-related mortality.  One monkey died at 0.5 mg/m3 and one
    at 2.3 mg/m3 due to accidental infections.  Body weight gain
    reduction was only found in rats at 2.3 and 4.1 mg/m3. 
    Clinically, ocular discharge and salivation were observed in dogs at
    2.3 and 4.1 mg/m3 and in monkeys at 4.1 mg/m3. Monkeys kept
    their eyes closed at 2.3 mg/m3.  No adverse effects on
    haematological or biochemical parameters were observed in any of the
    animals.  At necropsy, occasional pulmonary haemorrhage and focal
    necrosis in the liver were found in three rats at 2.3 mg/m3. 
    Pulmonary inflammation and occasional focal liver necrosis were also
    observed in guinea-pigs at this concentration.  Sections of lung
    from two of the four dogs exposed at 0.5 mg/m3 revealed focal
    vacuolization, hyperaemia, and increased secretion of bronchiolar
    epithelial cells, slight bronchoconstriction, and moderate
    emphysema. At 2.3 mg/m3, focal inflammatory reactions involved
    lung, kidney, and liver.  Bronchiolitis and early broncho-pneumonia
    were seen in one dog.  At 4.1 mg/m3, both dogs had confluent
    bronchopneumonia. All nine monkeys at 4.1 mg/m3 showed squamous
    metaplasia and six of them showed basal cell hyperplasia in the
    trachea.  None of the species revealed other treatment-related
    changes (Lyon  et al., 1970).

         Bouley  et al. (1975) exposed a total of 173 male SPF-OFA rats
    to a measured acrolein vapour concentration of 1.26 mg/m3 for a
    period of 15 to 180 days and used control groups of equal size.  No
    mortality occurred.  Sneezing was observed from day 7 to day 21 in
    the treated animals, and body weight gain and food consumption were
    reduced.  There was an increase in relative lung weight in rats
    killed on day 77 but not in rats killed on days 15 or 32.  The
    relative liver weight was decreased at day 15 but not thereafter,
    and the number of alveolar macrophages was decreased at days 10 and
    26 but not at days 60 or 180.  When groups of 16 rats were infected
    by one LD50 dose of airborne  Salmonella enteriditis on day 18 or
    day 63, mortality increased from 53% in controls to 94% in the
    exposed rats infected on day 18.  No changes were observed in
    biochemical parameters, including the amount of liver DNA per mg of
    protein in a group of partially hepatectomized rats, or in the
    response of spleen lymphocytes to phytohaemagglutinin in rats
    exposed for 39 to 57 days.  Other end-points were not investigated.

    7.2.2  Repeated inhalation exposure

         Lyon  et al. (1970) exposed groups of rats, guinea-pigs, dogs,
    and monkeys to acrolein vapour at concentrations of 0, 1.6. and
    8.5 mg/m3 for 8 h per day and 5 days per week over 6 weeks.  With
    the exception of the exposure levels, period, and frequency, the
    protocol was the same as that for the continuous inhalation exposure
    described in section 7.2.1.  Two deaths occurred among the nine
    monkeys at 8.5 mg/m3.  There was body weight gain reduction in
    rats and body weight loss (not statistically significant) in monkeys
    at 8.5 mg/m3. Clinically, eye irritation and salivation were
    observed in dogs and monkeys and difficult breathing in dogs at
    8.5 mg/m3.  No adverse effects on haematological or biochemical
    parameters were observed in any of the animals.  At necropsy,
    sections of lung from all animals exposed to 1.6 mg/m3 showed
    chronic inflammatory changes. Additionally, some showed emphysema. 
    At 8.5 mg/m3, squamous metaplasia and basal cell hyperplasia were
    observed in the trachea of both dogs and monkeys.  In addition,
    bronchopneumonia was noted in dogs and necrotizing bronchitis and
    bronchiolitis in monkeys.  Focal calcification of the tubular
    epithelium was noted in the kidneys of rats and monkeys at
    8.5 mg/m3.

         Groups of male Sprague-Dawley rats were also exposed to
    acrolein vapour at measured concentrations of 0, 0.39, 2.45, and
    6.82 mg/m3 for 6 h per day and 5 days per week over 3 weeks (Leach
     et al., 1987).  Subgroups were used for immunological
    investigations (section 7.4) and for histopathological examination
    of nasal turbinates and lungs.  Body weight gain was depressed from
    week 1 up to the end of the exposure period at 6.82 mg/m3. 
    Absolute, but not relative, spleen weight was reduced at this
    exposure level.  There were no histological effects on the lungs,
    but the respiratory epithelium of the nasal turbinates showed
    exfoliation, erosion, and necrosis, as well as dysplasia and
    squamous metaplasia at 6.82 mg/m3.  In addition, the mucous
    membrane covering the septum and lining the floor of the cavity
    showed hyperplasia and dysplasia (Leach  et al., 1987).

         Another experiment involved Dahl rats of two lines, one
    susceptible (DS) and one resistant (DR) to salt-induced hypertension
    (Kutzman  et al., 1984). Groups of 10 female rats of each line were
    exposed to measured acrolein concentrations of 0, 0.89, 3.21, and
    9.07 mg/m3 for 6 h per day and 5 days per week over 61-63 days. 
    One week after the exposure, survivors were killed for pathological
    and compositional analysis of the lung following behavioural and
    clinical chemistry testing.  At 9.07 mg/m3, all DS rats died
    within 11 days and 4 DR rats died within the exposure period. 
    Reduced body weights were measured in the surviving DR rats during
    the first 3 weeks, followed by an almost normal body weight gain. 
    Biochemical changes were found in DR rats at 9.07 mg/m3 and
    included increases in lung hydroxyproline and elastin, serum

    phosphorus, and in the activities of serum alkaline phosphatase,
    alanine aminotransferase (EC, and aspartate
    aminotransferase (EC  No effects were observed on
    exploratory behaviour, locomotor activity, blood pressure, lung
    protein, blood urea nitrogen, or on serum creatinine, uric acid, or
    calcium.   At necropsy of survivors, DR rats exposed to 9.07 mg/m3
    had increased relative weights of several organs, especially the
    lungs.  It was noted by the authors that the exposed rats gained a
    considerable amount of weight during the week following exposure. 
    In both rat lines, concentration-related increases were observed in
    lymphoid aggregates in pulmonary parenchyma, in collections of
    intra-alveolar macrophages with foamy cytoplasm, and in
    hyperplastic/metaplastic terminal bronchiolar epithelial changes. 
    Multifocal interstitial pneumonitis and squamous metaplasia of the
    tracheal epithelium were also found in DR rats exposed to
    9.07 mg/m3. In contrast, dead and moribund rats, especially those
    of the DS strain, mainly exhibited severe bronchial and bronchiolar
    epithelial necrosis with exfoliation, oedema, haemorrhage, and
    varying degrees of bronchopneumonia.  Adverse effects were absent in
    nasal turbinates and in non-pulmonary tissues (Kutzman  et al.,

         In follow-up studies, groups of 32 to 57 male Fischer-344 rats
    were exposed in exactly the same way as described for the Dahl rats. 
    Surviving rats were tested for pulmonary function one week after
    exposure and then killed and examined for compositional analysis,
    morphometry, and (in nine rats per group) pathological changes in
    the lung (Kutzman  et al., 1985; Costa  et al., 1986).  At
    9.07 mg/m3, 56% mortality occurred.  After an initial body weight
    loss over the first 10 days, weight gain became comparable to that
    of controls.  There was an increase in the relative weight of
    several organs, especially the lungs.  Lungs also showed an increase
    in water content and in the levels of elastin and hydroxyproline,
    but not in the levels of protein and DNA.  The hydroxyproline level
    was also elevated at 3.21 mg/m3.  Histologically, surviving rats
    treated with 3.21 or 9.07 mg/m3 demonstrated an exposure-related
    increase in effects on the respiratory tract consisting of
    bronchiolar epithelial necrosis with exfoliation, bronchiolar
    mucopurulent plugs, an increase in bronchiolar and alveolar
    macrophages, and focal pneumonitis.  At 3.21 mg/m3, there was
    type II cell hyperplasia and at 9.07 mg/m3 tracheal,
    peribronchial, and alveolar oedema and acute rhinitis.  The severity
    of lung lesions was highly variable and three of the nine rats
    examined at 9.07 mg/m3 did not exhibit histological damage. 
    Moribund rats mainly showed severe acute bronchopneumonia and focal
    alveolar and tracheal oedema with exfoliation in the bronchi and
    bronchioles (Kutzman  et al., 1985).  In another report from the
    same research group, the results of pulmonary function testing and
    morphometry disclosed air-flow dysfunction at 9.07 mg/m3, which
    was correlated with the presence of focal peribronchial lesions and
    the lung elastin concentrations.  In contrast, the rats exposed at

    0.89 mg/m3 exhibited enhanced flow-volume dynamics, whereas no
    effects on lung function were present in the 3.21-mg/m3 group
    (Costa  et al., 1986).

         Groups of six Wistar rats and ten Syrian golden hamsters of
    both sexes were exposed to acrolein vapour at measured
    concentrations of 0, 0.9, 3.2, and 11.2 mg/m3 for 6 h per day and
    5 days per week over 13 weeks (Feron  et al., 1978).  Within the
    first month of exposure to 11.2 mg/m3, half the number of rats of
    each sex died.  One hamster died at this exposure level because of
    renal failure. A treatment-related decrease in body weight gain and
    food intake was observed in rats exposed to 3.2 mg/m3 or more. 
    Hamsters showed decreased body weight gain at 11.2 mg/m3, but food
    intake was not examined.  At this exposure level, all animals kept
    their eyes closed, rats showed bristling hair, and hamsters showed
    salivation and nasal discharge.  Haematological investigation and
    urinalysis in week 12 showed no changes in rats.  In hamsters,
    urinalysis revealed no changes, but females showed increases in the
    number of erythrocytes, packed cell volume, haemoglobin content, and
    number of lymphocytes and a decrease in the number of neutrophilic
    leucocytes.  Changes in relative organ weights, which were
    considered by the authors to be related to the treatment, were found
    in the lung, heart, and kidneys of both species and in the adrenals
    of rats exposed to 11.2 mg/m3.  Histological changes were confined
    to the respiratory tract.  In the nose, rats exhibited an
    exposure-related increase in squamous metaplasia and neutrophilic
    infiltration of the mucosa at levels of 0.9 mg/m3 or more (at
    0.9 mg/m3 each effect was observed in one male) and occasional
    necrotizing rhinitis at 11.2 mg/m3.  Hamsters also showed these
    effects at 11.2 mg/m3 but only minimal inflammatory changes at
    3.2 mg/m3.  In the larynx and trachea of rats exposed to
    11.2 mg/m3, squamous metaplasia was also observed and was
    accompanied by hyperplasia in bronchi and bronchioli.  At this
    exposure level, the larynx of hamsters was slightly thickened and
    focal hyperplasia and metaplasia were found in the trachea. 
    Inflammatory changes were present in the bronchi, bronchioli, and
    alveoli of rats and included haemorrhage, oedema, accumulations of
    alveolar macrophages, an increase in mucus-producing cells in the
    bronchioli, and bronchopneumonia.  The authors noted considerable
    variation between individual rats in the degree of the lesions
    (Feron  et al., 1978).

         Feron & Kruysse (1977) exposed groups of 36 Syrian golden
    hamsters of both sexes to acrolein vapour at measured levels of 0
    and 9.2 mg/m3 for 7 h per day and 5 days per week over 52 weeks. 
    Except for 6 males and 6 females, the hamsters were observed for a
    further 29 weeks after the exposure period.  Overall mortality was
    38% in exposed hamsters and 33% in controls.  Body weight was
    slightly and reversibly decreased at the end of the exposure period. 
    The other effects observed at the end of the exposure period were
    essentially similar (but less severe) to those described above for

    hamsters exposed to 11.2 mg/m3 for 13 weeks, but hyperplasia was
    not observed.  Histological changes were restricted to the anterior
    half of the nasomaxillary turbinates and were still found in 20% of
    the animals at week 81.  At that time they mainly consisted of a
    thickened submucosa and exudation into the lumen.  Epithelial
    metaplasia, but not hyperplasia, was noted.  No tumours were found.

         Histopathological examination of the respiratory tract of male
    Swiss-Webster mice was the object of a study involving groups of 16
    to 24 male mice exposed to measured concentrations of 3.9 mg/m3
    for 6 h per day during 5 days (Buckley  et al., 1984).  The lesions
    observed were restricted to the nose and were most severe in the
    anterior respiratory epithelium and on the free margins of the
    nasomaxillary turbinates and the adjacent nasal septum.  They
    consisted of severe deciliation, moderate exfoliation, erosion,
    ulceration and necrosis, severe squamous metaplasia, moderate
    neutrophilic infiltration, and a slight serofibrinous exudate. 
    Lesions in the olfactory epithelium were largely confined to the
    dorsal meatus and consisted of moderate ulceration and necrosis, and
    slight squamous metaplasia.  The nasal squamous epithelium was not
    affected (Buckley  et al., 1984).

         One special investigation concerned the effects of acrolein
    vapour on the respiratory functions of male Swiss mice exposed to
    100 mg/m3 for two daily periods of 30 min each for 5 weeks.  Body
    weights were not affected.  There was a decrease in pulmonary
    compliance, but no effects were found on pulmonary resistance,
    respiratory volume, or functional residual capacity. The lungs
    showed an increase in phospholipid content (Watanabe & Aviado,1974).

         In summary, the toxicological effects on a variety of
    laboratory animals from repeated inhalation exposure to acrolein
    vapour at concentrations ranging from 0.39 mg/m3 to 11.2 mg/m3
    have been studied.  Exposure durations ranged from 5 days to as long
    as 52 weeks.  In general, body weight gain reduction, decrement of
    pulmonary function, and pathological changes in nose, upper airways,
    and lungs have been documented in most species exposed to acrolein
    concentrations of 1.6 mg/m3 or more.  Pathological changes include
    inflammation, metaplasia, and hyperplasia of the respiratory tract. 
    Significant mortality has been observed following repeated exposures
    to acrolein vapour at concentrations above 9.07 mg/m3.

    7.2.3  Repeated intraperitoneal exposure

         Groups of ten intact or adrenalectomized NMRI mice were
    injected intraperitoneally with saline or acrolein in water at daily
    doses of 4 to 16 mg/kg body weight for 1 to 6 days.  One week after
    the last injection the mice were killed for autopsy.

         Clinical signs of toxicity were hunched posture, inactivity,
    and ruffled fur.  Total body weight and relative thymus and spleen
    weights showed a dose-related reduction, while the adrenals showed
    an increase in relative weight.  Histologically, thymic necrosis and
    splenic atrophy were the only changes observed.  These changes were
    absent in controls and in adrenalectomized mice. The levels of
    reduced glutathione and the activity of glutathione  S-transferase
    in liver cytosol were unchanged, but the rate of glutathione
    synthesis was increased.  Repeated exposure to acrolein caused a
    progressively less pronounced effect on mortality (Warholm  et al.,

    7.3  Biochemical effects and mechanisms of toxicity

    7.3.1  Protein and non-protein sulfhydryl depletion

         A dose-related non-protein sulfhydryl (reduced glutathione)
    depletion was observed in the nasal respiratory mucosa of male
    Fischer rats after nose-only exposure for 3 h to acrolein vapour at
    concentrations of 0.23-11.4 mg/m3 (McNulty  et al., 1984; Lam
     et al., 1985).  Depletion of glutathione in the liver was not
    observed at these exposure levels (McNulty  et al., 1984). The
    glutathione depletion in the nasal mucosa appeared irreversible at
    11.4 mg/m3 (McNulty  et al., 1984). In female C3Hf/HeHa mice,
    intraperitoneally exposed once to doses between 20 and 80 mg/kg body
    weight and killed 2 h later, a dose-related decrease in liver
    glutathione levels was observed. These doses are however extremely
    high considering the fact that a dose of 4.5 mg/kg body weight was
    lethal within 1.7 h (Gurtoo  et al., 1981a).

         A dose-related  in vitro glutathione depletion has been
    observed in human bronchial fibroblasts (Krokan  et al., 1985),
    human bronchial epithelial cells (Grafström  et al., 1988), human
    chronic myeloid leukemia cells (Crook  et al., 1986b), and human
    and rat phagocytic cells (Witz  et al., 1987) from the lowest
    acrolein concentration tested (56 µg/litre).  The effect has also
    been reported to occur in isolated rat hepatocytes (Zitting &
    Heinonen, 1980; Dawson  et al., 1984; Dore & Montaldo, 1984; Ku &
    Billings, 1986) and in rat liver or lung microsomal suspensions
    (Patel  et al., 1984), the lowest-observed-effect level being
    1400 µg/litre (Dawson  et al., 1984).  Ku & Billings (1986)
    observed that both mitochondrial and cytosolic glutathione levels
    were decreased.

         As a result of acrolein exposure, there was a decrease in the
    level of both membrane surface and soluble protein sulfhydryl groups
    in  in vitro human and rat phagocytic cells (Witz  et al., 1987)
    and a decrease in the level of soluble protein sulfhydryl compounds
    in human bronchial epithelial cells (Grafström  et al., 1988). 
    Acrolein has also been shown to cause a decrease in membrane surface
    protein sulfhydryl groups in rat hepatocytes (Ku & Billings, 1986)

    and to reduce the protein sulfhydryl content of liver and lung
    microsomal preparations (Patel  et al., 1984).

    7.3.2  Inhibition of macromolecular synthesis

         When partially hepatectomized Wistar rats were exposed
    intraperitoneally to a single acrolein dose of 0.5, 1.6, 2.0, or
    2.7 mg/kg body weight, a dose-related inhibition of the synthesis of
    DNA and RNA was measured in liver and lung cells (Munsch &
    Frayssinet, 1971).

         Inhibition of DNA, RNA, and/or protein synthesis has been
    observed in  Escherichia coli (Kimes & Morris, 1971), the slime
    mold  Physarum polycephalum (Leuchtenberger  et al., 1968), the
    alga  Dunaliella bioculata (Marano & Puiseux-Dao, 1982), and in
     in vitro mammalian cells such as mouse kidney cells (Leuchtenberger
     et al., 1968) and polyoma transformed Chinese hamster cells
    (Alarcon, 1972).  Acrolein was shown to inhibit RNA polymerase in
    isolated rat liver nuclei (Moule & Frayssinet, 1971) and isolated
    rat liver DNA polymerase (Munsch  et al., 1973).  The activity of
    the latter enzyme is associated with at least one functional
    sulfhydryl group, and preincubation of the enzyme with
    2-mercaptoethanol protected against the inhibitory action of
    acrolein.  Since acrolein did not inhibit isolated  Escherichia coli
    polymerase I, devoid of sulfhydryl groups in its active centre,
    Munsch  et al. (1973) suggested that the inhibitory action of
    acrolein is caused by a reaction with sulfhydryl groups.

    7.3.3  Effects on microsomal oxidation

         In  in vitro studies, acrolein has been shown to convert rat
    liver cytochrome P-450 to cytochrome P-420 and to inhibit rat liver
    NADPH-cytochrome-c reductase (EC in a time- and
    concentration-related fashion (Marinello  et al., 1978; Ivanetich
     et al., 1978; Berrigan  et al., 1980; Gurtoo  et al., 1981b;
    Marinello  et al., 1981; Patel  et al., 1984; Cooper  et al.,
    1987).  A concomitant decrease occurred in the activity of several
    monooxygenases: benzphetamine  N-demethylase, aniline hydroxylase,
    ethylmorphine  N-demethylase (Patel  et al., 1984), and
    7-ethoxyresorufin  O-deethylase (Cooper  et al., 1987).  The
    lowest-observed-effect levels reported were 2 mg/litre for
    inactivation of cytochrome P-450 (Gurtoo  et al., 1981b) and
    25 mg/litre for inhibition of NADPH-cytochrome- c reductase
    (Marinello et al.,1981).  It was also shown that the addition of
    sulfhydryl-containing agents, such as cysteine, acetylcysteine,
    glutathione, dithiothreitol, and semicarbazide, reduced the above
    effects, suggesting that acrolein produces them by reacting with
    sulfhydryl groups at the active sites.

    7.3.4  Other biochemical effects

          In vivo studies with Holtzman rats have shown that rat liver
    alkaline phosphatase (EC and tyrosine aminotransferase
    (EC activities are increased markedly after inhalation of
    acrolein for 4 h at a concentration of 14.7 mg/m3 or after a
    single intraperitoneal injection of acrolein in water at doses of
    1.5-6 mg/kg body weight (Murphy  et al., 1964; Murphy, 1965).  The
    increase in alkaline phosphatase activity following intraperitoneal
    injection was shown to be dose related (Murphy, 1965).  The effects
    were reduced by prior adrenalectomy or hypophysectomy or by
    pretreatment with protein synthesis inhibitors such as actinomycin
    D, puromycin, and ethionine, suggesting that the irritant action of
    acrolein stimulates the pituitary-adrenal system to release
    glucocorticoids, which act to increase the synthesis of adaptive
    liver enzymes (Murphy, 1965; Murphy & Porter, 1966). Increased
    plasma and adrenal levels of corticosterone were measured in
    Holtzman rats one hour after a single intraperitoneal injection
    (3 mg/kg body weight) of acrolein in water (Szot & Murphy, 1971). 
    The hypersecretion of glucocorticoids could also explain the
    observed increase in liver glycogen level following intraperitoneal
    exposure to acrolein at a dose of 1.5 mg/kg body weight (Murphy &
    Porter, 1966).

         At a concentration of 5.6 mg/litre, acrolein produced an 80%
    inhibition of the noradrenaline-induced oxygen consumption of
    isolated hamster brown fat cells (Pettersson  et al., 1980).  In
    addition, Zollner (1973) observed an acrolein-induced inhibition of
    the respiration of intact rat liver mitochondria and found evidence
    for an inhibition at three different sites: glutamate transport,
    inorganic phosphorus transport, and the enzyme succinic
    dehydrogenase (EC

         Several sulfhydryl-sensitive enzymes have been shown to be
    inhibited by acrolein  in vitro, e.g., rabbit muscle L-lactate
    dehydrogenase (EC, yeast glucose-6-phosphate
    dehydro-genase (EC, and yeast alcohol dehydrogenase
    (EC (Benedict & Stedman, 1969), porcine lung
    15-hydroxyprosta-glandin dehydrogenase (EC (Liu & Tai,
    1985), rat liver or urothelium  S-adenosyl-L-methionine-
    DNA(cytosine-5)- methyltransferase (EC (Cox  et al.,
    1988), and  O6-methylguanine-DNA methyltransferase (EC
    in cultured human bronchial fibroblasts (Krokan et al, 1985).  In
    two of these studies glutathione was shown to afford protection
    against inhibition of the enzyme (Liu & Tai, 1985; Cox  et al.,

         It has been suggested that the formation of a Schiff base
    between acrolein and sensitive amine groups is responsible for the
    observed inhibition  in vitro of Salmonella typhimurium
    deoxyribose-5-phosphate aldolase (EC at a concentration of

    approximately 14 mg/litre (Wilton, 1976) and human plasma
    alpha1-proteinase inhibitor (Gan & Ansari, 1987).

         Acrolein was shown to cause a concentration-dependent increase
    in lipid peroxidation in isolated rat hepatocytes at levels that
    also decreased glutathione concentrations (Zitting & Heinonen,
    1980).  Preincubation of washed rat liver microsomes with acrolein
    abolished the protective effect of glutathione against
    iron/ascorbate-induced lipid peroxidation (Haenen et al, 1988).  The
    authors claimed that the protective effect of glutathione was
    mediated by vitamin E scavenging membrane lipid radicals.  It was
    suggested that acrolein was inhibiting a glutathione-dependent
    reductase enzyme responsible for reducing vitamin E radicals back to
    vitamin E.

    7.4  Immunotoxicity and host resistance

         Acrolein has been found to depress pulmonary host defenses in a
    number of tests.

         In female Swiss mice, exposed to measured concentrations of
    1.1, 6.9, and 14.2 mg/m3 for 8 h, a concentration-related increase
    in the survival of  Staphylococcus aureus was seen at levels of
    6.9 mg/m3 or more (Astry & Jakab, 1983).  A concentration- and
    time-related increase in the  survival of  S. aureus and  Proteus
     mirabilis was found in male Swiss CD-1 mice exposed to measured
    concentrations of 2.3 to 4.6 mg/m3 for 24 h. When the mice were
    also infected with Sendai virus, intrapulmonary bacterial death was
    further suppressed (Jakab, 1977).  An increased survival of
     Klebsiella pneumoniae, but no increased mortality from pneumonia
    following challenges with  Streptococcus zooepidemicus, was
    observed in female CD-1 mice after exposure to acrolein at a
    measured concentration of 0.23 mg/m3 for 3 h per day over 5 days
    (Aranyi  et al., 1986).  In female CR/CD-1 mice, exposure to a
    measured acrolein concentration of 4.6 mg/m3, for one period of
    6 h or for 7 consecutive daily periods of 8 h, resulted in an
    increased mortality from  Streptococcus pyogenes and Salmonella
    typhimurium, respectively, but not from influenza A virus (Campbell
     et al., 1981).

         Sherwood  et al. (1986) exposed groups of 33 male
    Sprague-Dawley rats to acrolein vapour at analysed concentrations of
    0.39, 2.45 or 6.82 mg/m3 for 3 weeks (6 h per day and 5 days per
    week).  The relative pulmonary bactericidal activity to
     K. pneumoniae was not affected nor was the number of alveolar
    cells.  However, the number of peritoneal macrophages was decreased
    at concentrations of 2.45 mg/m3 or more, and alveolar and
    peritoneal macrophages had altered phagocytic and enzymic patterns
    at > 0.39 mg/m3.

         When SPF-OFA rats were exposed continuously to a measured
    acrolein concentration of 1.26 mg/m3 for 18 days, they exhibited
    an increased mortality from an infection by  Salmonella enteritidis. 
    However, no such effect was observed following 63 days of exposure
    (Bouley  et al., 1975).

         Acrolein has been shown to inhibit  in vitro protein synthesis
    (Leffingwell & Low, 1979), and phagocytosis and ATPase (EC activity (Low  et al., 1977) in rabbit pulmonary
    alveolar macrophages.  Inhibition of a graft-versus-host reaction in
    rats was found after Wistar rat spleen cells were incubated
     in vitro with acrolein and injected into all four feet of hybrid
    F1 rats.  In addition, a decreased mitogen response of human
    peripheral lymphocytes was recorded (Whitehouse  et al., 1974). 
    Acrolein was also found to inhibit  in vitro chemotaxis of human
    polymorphonuclear leucocytes (Bridges  et al., 1977).

    7.5  Reproductive toxicity, embryotoxicity, and teratogenicity

         Two  in vivo exposure studies have been reported.  In one, 3
    male and 21 female SPF-OFA rats were exposed continuously to
    acrolein vapour at a measured concentration of 1.26 mg/m3 for 25
    days and allowed to mate on day 4. It should be noted that the
    exposure period did not cover the complete spermatogenic period of
    60 days.  The number of pregnant animals and the number and mean
    weight of the fetuses were unaffected in comparison to the control
    rats (Bouley  et al., 1985).  In the second study, groups of 12 to
    16 New Zealand rabbits were injected (into the ear vein) with a
    solution of acrolein in saline (3, 4.5 or 6 mg/kg body weight) on
    the 9th day of gestation.  At 4.5 and 6 mg/kg body weight, maternal
    toxicity was indicated by the death of 3 and 6 dams, respectively,
    and embryotoxicity by a dose-related increase in resorptions which
    was significant at 6 mg/kg body weight.  It was also reported that
    the number of malformed and retarded fetuses increased in a
    dose-related manner, although the increases were statistically
    non-significant.  No effects on maternal toxicity, embryotoxicity or
    fetuses were noted at 3 mg/kg body weight (Claussen  et al., 1980).

         A clear effect on the development of the embryo  in vivo was
    observed only when acrolein was administered close to the target
    site by intra-amniotic injection.  Using groups of 12 to 19 pregnant
    New Zealand rabbits, 0, 10, 20, or 40 µl of a 0.84% solution of
    acrolein in saline was injected into the amnion of all embryos in
    one of the uterine horns on the 9th day of gestation. The embryos in
    the other uterine horn received saline only and served as controls.
    The dams were killed on day 28 of gestation.  There was a
    dose-related increase in the rate of resorptions and malformations,
    significant at doses of 20 µl or more per embryo.  Malformations
    included deformed and asymmetric vertebrae, spina bifida, deformed
    and fused ribs, and lack or fusion of sternum segments.  No effect
    was observed on the number of implantations and fetuses or on fetal
    growth (Claussen  et al., 1980).  A similar study was carried out

    on pregnant Sprague-Dawley rats injected with acrolein doses of 0,
    0.1, 1.0, 2.5, 5.0, 10.0 or 100 µg per fetus in 10 ml of saline on
    the 13th day of pregnancy.  The dams were killed on day 20 of
    gestation. A dose-related increase in the percentage of dead and
    resorbed fetuses per litter was observed at all dose levels.  The
    total number of litters at each dose level varied from 4 to 18.  The
    percentage of malformed fetuses per litter also was increased in a
    dose-related manner at doses of up to 5 µg per fetus. The increase
    was significant only up to this dose level, probably because at
    higher doses there were few surviving fetuses. Treatment-related
    effects included oedema, micrognathia, hindlimb and forelimb
    defects, and hydrocephaly (Slott & Hales, 1985). These results
    confirmed the findings of an earlier, identical test using dose
    levels of 0.1, 10, and 100 µg per fetus (Hales, 1982).

         Acrolein was also shown to be embryotoxic and teratogenic in
    the rat whole embryo culture system. As with embryos exposed in
    vivo, the concentration range for teratogenicity was very narrow
    (Slott & Hales, 1986).  Schmid  et al. (1981) and Mirkes  et al.
    (1984) observed embryotoxicity but no teratogenicity in the same
    test system, this being probably the result of the different test
    conditions used (Slott & Hales, 1986).  Depletion of glutathione by
    buthionine sulfoximine enhanced the embryotoxicity and
    teratogenicity of acrolein in the  in vitro studies of Slott &
    Hales (1987a), whereas exogenous glutathione afforded protection
    against these effects (Slott & Hales, 1987b).

         In a mouse limb bud culture system, acrolein induced impairment
    of limb bud differentiation, indicative of a teratogenic action
    (Stahlmann  et al., 1985). When acrolein was injected into chicken
    eggs, embryotoxic and teratogenic effects were observed (Kankaanpaa
     et al., 1979; Korhonen  et al., 1983; Chhibber & Gilani, 1986).

         In summary, acrolein can induce teratogenic and embryotoxic
    effects if administered directly to the embryos or fetuses. 
    However, the fact that no effect was found in rabbits injected
    intravenously with 3 mg/kg suggests that neither skin contact nor
    inhalation of acrolein is likely to affect the developing embryo.

    7.6  Mutagenicity and related end-points

    7.6.1  DNA damage

          In vitro studies have revealed interactions between acrolein
    and DNA and RNA (Munsch  et al., 1974b; section 6.2.1).  Acrolein
    has also been found to react with purine and pyrimidine bases or
    intact DNA in vitro, and several adducts have been identified
    (Descroix, 1972; Hemminki  et al., 1980; Lutz  et al., 1982; Chung
     et al., 1984; Shapiro  et al., 1986; section  Cyclic
    deoxyguanosine DNA adducts were formed in a dose-dependent fashion
    in acrolein-exposed Salmonella typhimurium TA100 and TA104.  This

    adduct formation correlated with the induction of reverse mutations
    in these strains (section 7.6.2; Foiles  et al., 1989).

         No data on the formation of DNA adducts following exposure of
    animals to acrolein are available.

         Incubation of Fischer-344 rat nasal mucosal homogenate with
    acrolein resulted in a concentration-dependent increase in
    DNA-protein cross-linking, which was not observed following
    inhalation exposure of rats to acrolein at a concentration of
    4.6 mg/m3 for 6 h (Lam  et al., 1985).  According to the authors
    this could be explained by the preferential reaction of acrolein
    with sulfhydryl groups.  DNA-protein cross-linking and single strand
    breaks were observed  in vitro in human bronchial fibroblasts at
    cytotoxic concentrations of 1.7 mg/litre or more (Grafström  et al.,
    1986, 1988), and there was indirect evidence for some formation of
    DNA interstrand cross-linking (Grafström  et al., 1988).  No
    DNA-protein or DNA interstrand cross-linking was induced by acrolein
    in mouse L1210 leukemia cells at cytotoxic levels that  produced
    single strand breaks and/or alkali-labile sites in these cells
    (Erickson  et al., 1980) or in human chronic myeloid leukemia cells
    (Crook  et al., 1986a).  In non-mammalian assays, Fleer & Brendel
    (1982) did not find DNA interstrand cross-linking or single strand
    breaks in MB1072-2B yeast cells and Kubinski  et al. (1981)
    observed DNA-cell binding in  Escherichia coli in the presence of a
    rat liver S9 fraction.  These studies demonstrate that effects on
    DNA occur only at cytotoxic concentrations of acrolein.

         Results of DNA repair tests are not available. Acrolein has
    been demonstrated to inhibit  O6-methylguanine-DNA
    methyltransferase (EC; section 7.3.4) and, therefore, can
    be expected to reduce the capacity for repair of  O6-guanine
    alkylations in DNA (Krokan  et al., 1985).

    7.6.2  Mutation and chromosomal effects

         The results of tests for the induction of gene mutations and
    chromosome damage by acrolein are summarized in Table 10.

         In point mutation assays with Salmonella typhimurium, the
    positive or equivocal responses obtained were all observed within a
    narrow dose range of up to 10-56 µg per plate, higher doses being
    toxic. Clearly positive, dose-related increases in revertant
    colonies per plate at 2-5 times the background rate were observed in
    the absence of metabolic activation only in TA100 (Lutz  et al.,
    1982; Foiles  et al., 1989; Hoffman  et al., 1989), TA104 (Marnett
     et al., 1985; Foiles  et al., 1989; Hoffman  et al., 1989), and
    TA98 (Lijinsky & Andrews, 1980).  Khudoley  et al. (1986) reported
    positive results in strains TA98 and TA100 without specifying dose
    levels or revertant rates.  Some evidence for indirect mutagenicity
    was found in strains TA1535 (Hales, 1982) and TA100 (Haworth

     et al., 1983), the slight increase in TA100 revertants being dose
    related.  However, negative results, both with and without metabolic
    activation, have also been obtained in these strains.  Some of these
    negative results were clearly related to the incubation conditions,
    which were probably highly toxic, e.g., those obtained in spot tests
    (Andersen  et al., 1972; Florin  et al., 1980).  In Salmonella
    typhimurium TA100 and TA104, strains that show a clear mutagenic
    response to acrolein, DNA-acrolein adducts have also been identified
    (section 7.6.1).

         Acrolein did not induce sex-linked recessive lethality in
     Drosophila melanogaster adults (Zimmering  et al., 1985), but
    induced a 12-fold increase in sex-linked recessive lethality in
    hatching eggs and larva at an exposure level that was not reported
    but caused over 75% larval death (Rapoport, 1948). In the latter
    test, treatment of adults was reported to be less effective.

         Three cytogenetic tests have been carried out with acrolein,
    two in Chinese hamster ovary cells (Au  et al., 1980; Galloway
     et al., 1987) and one in human lymphocytes (Wilmer  et al.,
    1986).  Acrolein was shown to induce sister chromatid exchanges in
    the absence of a metabolic activating system in all three studies. 
    The lowest effective concentration was 56 µg/litre (Galloway
     et al., 1987).  No increase in chromosome aberrations was reported
    in one study (Galloway  et al., 1987), while chromosome breakage
    was reported in another study at cytotoxic concentrations (Au
     et al., 1980).

         Three properties of acrolein make it difficult to test for
    mutagenicity: its high cytotoxicity, which prevents the expression
    of any mutagenic activity, and its high reactivity and volatility,
    which prevent it reaching the target sites.  However, acrolein can
    be considered to be a weak mutagen in some bacterial and fungal test
    systems in the absence of metabolic activating systems  and to
    induce sister chromatid exchange in cultured mammalian cells.

    7.6.3  Cell transformation

         Acrolein (0.4 µg/ml) has been found not to exhibit transforming
    potential in C3H/10T1/2 cells but to initiate the process of
    transformation. The latter was measured by exposing cultures to
    acrolein for 24 h and, subsequently, to a phorbol ester for 6 weeks
    (Abernethy  et al., 1983).

        Table 10.  Tests for gene mutation and chromosomal damage by acrolein


    Test description      Organism     Species/strain/cell type                Resulta    Reference


    Gene mutations

    Reverse mutations     bacteria     Salmonella typhimurium TA1535           ±(+S9)     Hales (1982)
                                                                                  -       Florin et al. (1980); Loquet et al. (1981);
                                                                                          Haworth et al. (1983); Lijinsky & Andrews (1980)
                                       Salmonella typhimurium TA100            +(-S9)     Lutz et al. (1982); Khudoley et al., 1986;
                                                                                          Foiles et al. (1989); Hoffman et al. (1988)
                                                                               ±(+S9)     Haworth et al. (1983)
                                                                                  -       Florin et al. (1980); Loquet et al. (1981);
                                                                                          Basu & Marnett (1984); Lijinsky & Andrews (1980)
                                       Salmonella typhimurium TA104            +(-S9)     Marnett et al. (1985); Foiles et al. (1989);
                                                                                          Hoffman et al. (1989)
                                       Salmonella typhimurium TA102               -       Marnett et al. (1985)
                                       Salmonella typhimurium TA98             +(-S9)     Lijinsky & Andrews (1980); Khudoley et al. (1986)
                                                                                  -       Florin et al. (1980); Loquet et al. (1981);
                                                                                          Haworth et al. (1983); Basu & Marnett (1984)
                                       Salmonella typhimurium TA1537              -       Florin et al. (1980); Haworth et al. (1983);
                                                                                          Lijinsky & Andrews (1980)
                                       Salmonella typhimurium TA1538              -       Basu & Marnett (1984); Lijinsky & Andrews (1980)
                                       Salmonella typhimurium, 8 strains          -       Andersen et al. (1972)
                                       Escherichia coli 343/113                   -       Ellenberger & Mohn (1976, 1977)b
                                       Escherichia coli WP2 uvrA               ±(-S9)     Hemminki et al. (1980)
                          yeast        Saccharomyces cerevisiae S211, S138        -       Izard (1973)
    Forward mutations     yeast        Saccharomyces cerevisiae N123           +(-S9)     Izard (1973)c

    Table 10 (contd).


    Test description      Organism     Species/strain/cell type                Resulta    Reference


    Forward mutations     man          normal fibroblasts                      -(-S9)     Curren et al. (1988)
                                       DNA-repair-deficient fibroblasts        +(-S9)     Curren et al. (1988)
                          hamster      V79 cells                               +(-S9)     Smith et al. (1990)

    Sex-linked lethal     insect       Drosophila melanogaster, hatching          +       Rapoport (1948)d
    mutations                          eggs and young larva
                                       Drosophila melanogaster, adults            -       Zimmering et al. (1985)e

    Chromosomal damage

    Aberrations           hamster      ovary cells in vitro                    ±(+S9)     Au et al. (1980)
                                                                               ±(-S9)     Galloway et al. (1987)

    Sister chromatid      hamster      ovary cells in vitro                    +(-S9)     Au et al. (1980)
    exchanges                                                                  +(-S9)     Galloway et al. (1987)
                          man          lymphocytes in vitro                    +(-S9)     Wilmer et al. (1986)

    Dominant lethal       mouse        germ cells                                 -       Epstein & Shafner (1968)
    (ip exposure)

    a   + = >2 x background rate or statistically significant (P < 0.05); ± = equivocal; - = negative.
    b   Details for this test were not reported.
    c   Plate test for  petite mutations (production of a respiratory-deficient mutant).
    d   Doses were not reported.  Treatment of adults was found to be less effective.
    e   Exposure via feeding solution or via injection.

    7.7  Carcinogenicity

    7.7.1  Inhalation exposure

         Inhalation experiments of appropriate duration specifically
    designed to assess the carcinogenicity of acrolein vapour have not
    been conducted.

         An 81-week study (52 weeks of acrolein exposure at 9.2 mg/m3
    followed by 29 weeks without exposure) on groups of 36 Syrian golden
    hamsters of both sexes is described in section 7.2.2.  The effects
    of treatment included a persistent and statistically significant
    reduction in body weight in females, an increased relative brain
    weight in males and females at 52 weeks, and an increased relative
    lung weight in females at 52 weeks.  Apart from one small tracheal
    papilloma in an acrolein-exposed female, no respiratory tract
    tumours were observed in control or treated hamsters (Feron &
    Kruysse, 1977).  In order to elucidate a possible co-carcinogenic
    action of acrolein, Feron & Kruysse (1977) also exposed groups of 30
    Syrian golden hamsters of both sexes to measured acrolein vapour
    concentrations of 0 or 9.2 mg/m3, 7 h per day and 5 days per week
    for 52 weeks, and, for the same period, either weekly to an
    intratracheal dose of benzo [a]pyrene or once every 3 weeks to a
    subcutaneous dose of diethylnitrosamine. Total dose levels were 18.2
    or 36.4 mg benzo [a]pyrene and 2.1 µl diethylnitrosamine. Survivors
    were killed at week 81, and all hamsters were subjected to
    postmortem examination.  The mortality rate in the groups treated
    with benzo [a]pyrene was slightly higher than in other groups. The
    incidence of benzo [a]pyrene-induced respiratory tract tumours was
    slightly (but statistically insignificantly) higher in females also
    exposed to acrolein vapour.  In these females, at the higher dose
    level of benzo [a]pyrene, respiratory tract tumours occurred
    earlier and the number of malignant tumours was slightly increased. 
    Taken together, these observations might suggest an enhancing effect
    of acrolein on benzo [a]pyrene carcinogenesis in the respiratory
    tract, but the effect cannot be considered proven.

         In a study by Le Bouffant  et al. (1980), rats, 20 animals per
    group, were exposed to 18.3 mg/m3, 1 h/day and 5 days/week, for 10
    or 18 months.  No tumours or metaplasias were found.

    7.7.2  Oral exposure

         In a study by Lijinsky & Reuber (1987), groups of 20
    Fischer-344 rats of both sexes were exposed to weekly prepared
    acrolein of unspecified purity in drinking-water. Each cage of four
    rats received 80 ml of acrolein solutions at concentrations of 100
    or 250 mg/litre for 124 weeks (males only) or 625 mg/litre for 104
    weeks (both sexes) for 5 days per week (this was estimated by the
    Task Group to be equivalent to approximately 5, 12.5, and 50 mg/kg
    body weight per day, respectively).  Total doses were 1200, 3100,

    and 6500 mg per rat, respectively. Controls were left untreated. 
    Survivors were killed at week 123-132 and all rats were subjected to
    postmortem examination.  The mean survival time was about 120 weeks
    for experimental and control groups.  There was a marginal, but not
    statistically significant, increase in the incidence of adrenal
    cortical adenomas (5/20) in female rats at 625 mg/litre, compared to
    concurrent controls (1/20), and a decrease in the incidence of
    pituitary neoplasms in both sexes at 625 mg/litre.  In addition, 2
    of 20 females given 625 mg/litre had hyperplastic nodules of the
    adrenal cortex.  The authors cited historic control values for
    adrenal cortical adenomas or carcinomas in female Fischer-344 rats
    from other laboratories as 1.3% at 26 months of age and 4.8% in a
    lifespan study.  Because of limited numbers of animals used and
    concerns regarding the purity and stability of acrolein in the dosed
    drinking-water, the authors of this study did not consider it to be
    a definitive carcinogenicity bioassay.  In addition, the Task Group
    considered the historical control values quoted by the authors to be
    of limited use in evaluating the importance of the tumour incidence
    found in this study.

         Acrolein appeared to be too toxic to Syrian golden hamsters
    following oral exposure by gavage in corn oil to conduct an
    effective carcinogenicity study (Lijinsky & Reuber, 1987).

    7.7.3  Skin exposure

         In a study by Salaman & Roe (1956), a group of 15 S strain mice
    of unspecified sex and age received weekly doses of 0.5% acrolein in
    acetone for 10 weeks. The total dose was 12.6 mg per rat, although
    the purity of the acrolein was not reported. The control group
    comprised 20 mice.  From day 25 after the first acrolein treatment,
    the mice received once per week a skin application of 0.17% croton
    oil (0.085% in weeks 2 and 3) for 18 weeks. Croton oil and acrolein
    were applied alternately at 3 or 4 day intervals. At the end of
    treatment, the mortality rate and the incidence of skin papillomata
    were similar to those of the controls treated only with croton oil. 
    However, this study must be considered inadequate because of the
    limited number of animals used and the short duration of the

    7.8  Interacting agents

         Free sulfhydryl-containing compounds have been found to give
    protection against the adverse effects of acrolein  in vitro, e.g.,
    the inhibition of enzymes involved in macromolecular synthesis
    (Munsch  et al., 1973), liver microsomal cytochrome P-450s
    (Marinello  et al., 1978; Berrigan  et al., 1980; Gurtoo  et al.,
    1981b, Patel  et al., 1984; Cooper  et al., 1987), and several
    other sulfhydryl-sensitive enzymes (Liu & Tai, 1985; Cox  et al.,
    1988), the adverse effects on rabbit alveolar macrophages (Low  et
     al., 1977; Leffingwell & Low, 1979), and the impairment of mouse
    limb bud differentiation (Stahlmann  et al., 1985). Free
    sulfhydryl-containing agents protected against the acute lethal
    effects of acrolein in Charles River rats (Sprince  et al., 1979)
    and in DBA/2J mice (Gurtoo  et al., 1981a).

         When Swiss-Webster mice were exposed to acrolein-formaldehyde
    mixtures, the percentage decrease in respiratory rate was found to
    be less than the sum of the percentage decreases due to each
    compound alone (Kane & Alarie,1978). In acrolein-exposed Fischer-344
    rats, pretreatment with formaldehyde resulted in a lower percentage
    decrease in respiratory rate compared to non-pretreated rats (Babiuk
     et al., 1985). It was suggested in both investigations that
    acrolein and formaldehyde competed for the same receptor
    (competitive agonism). In a comparable experiment, the maximum
    percentage decrease in the respiratory rate of Swiss-Webster mice
    exposed to a mixture of acrolein and sulfur dioxide was lower than
    that of acrolein alone. This antagonistic effect was thought to be
    caused by a chemical reaction in the air phase between the two
    compounds, which reduced the effective concentrations (Kane &
    Alarie, 1979).

         In Fischer-344 rats exposed to formaldehyde vapour
    (7.4 mg/m3) once for 6 h, co-exposure to acrolein vapour
    (4.6 mg/m3) resulted in a higher increase in DNA-protein
    cross-linking than was observed with formaldehyde alone. Acrolein
    alone did not increase DNA-protein cross-linking in this experiment
    (Lam  et al., 1985).

         In a study by Hales  et al. (1988), anaesthetized,
    artificially ventilated mongrel dogs were exposed to acrolein or
    hydrochloric acid with added synthetic smoke composed of carbon
    particles for 10 min.  The dogs were exposed to smoke with or
    without analytically determined acrolein concentrations of <
    458 mg/m3, 458-687 mg/m3 or > 687 mg/m3.  Smoke with
    acrolein, but not smoke with hydrochloric acid, produced
    non-cardiogenic, peribronchiolar pulmonary oedema in a
    concentration- and time-related fashion.  Both acrolein and
    hydrochloric acid produced airway damage consisting of mucosal
    degeneration and desquamation and inflammatory cell infiltration. 
    Acrolein at levels above 458 mg/m3 also caused fibrin deposition
    in the alveolar spaces that juxtaposed injured bronchioles.


    8.1  Single exposure

    8.1.1  Poisoning incidents

         One man was exposed dermally and by inhalation when acrolein
    was sprayed into his face following an accident in a chemical plant.
    Immediately, his face and eyelids were burnt. Within 20 h he was
    hospitalized with fever, cough, frothy sputum, cyanosis, and acute
    respiratory failure. Two months after the accident, the opening of
    the right bronchus was obstructed and the upper trachea showed
    slight oedema with haemorrhagic spots. At 18 months he had developed
    chronic bronchitis and emphysema, which might have been a sequel of
    the accidental exposure (Champeix  et al., 1966).

         One case of attempted oral suicidal intoxication has been
    reported. The man swallowed approximately 1.5 g of acrolein in a
    glass of orange juice. Blood was found in his stomach and the number
    of red and white blood cells was increased.  Gastroscopic
    examination showed shrinkage of the stomach and a massive chronic
    gastritis with erosions and ulceration. Further examination of the
    stomach revealed regenerating mucous membranes, few mucous glands,
    granulation and scarring of the serosa, shrinkage and stenosis of
    the pylorus, lymphadenitis, and haemosiderin deposition in lymph
    nodes. The man was successfully treated by gastrectomy (Schielke,

         Two cases of suspected exposure to acrolein have been reported. 
    The death of two young boys who inhaled smoke from an overheated
    frier for approximately 2 h was thought to be related to acrolein
    exposure, although other chemicals might also have been involved.
    One of the boys was found dead, while the other suffered from acute
    respiratory failure.  Following oxygen therapy, the second boy died
    due to asphyxia. At autopsy a massive cellular desquamation of the
    bronchial lining was observed.  The tracheal and bronchial lumina
    were filled with debris and the lungs showed multiple infarcts
    (Gosselin  et al., 1979).

         Four female factory workers operating a machine for cutting and
    sealing polyethylene bags and a fifth sitting next to the machine
    complained of a burning sensation in the eyes, a feeling of dryness
    and irritation in the nose and throat, and itching and irritation of
    the skin of the face, neck and forearms. These complaints were
    related to the smoke developed.  The presence of formaldehyde and
    "acrolein and/or other aldehydes" in the smoke was suspected and
    confirmed. During heavy smoke exposure, itching eruptions developed
    on exposed skin. Drowsiness and headache was also experienced. All
    symptoms were reversible (Hovding, 1969).

    8.1.2  Controlled experiments  Vapour exposure

         Several studies with volunteers have been conducted with the
    object of establing thresholds for odour perception and recognition
    and for effects on the eyes, nose, respiratory tract, and nervous
    system. The results of these studies are summarized in Table 11. The
    exposure period was up to 60 min.  In most cases the concentration
    of acrolein was determined colorimetrically, although a few reports
    did not include a description of the analytical method (Plotnikova,
    1957; Sinkuvene, 1970; Harada, 1977).  Sinkuvene (1970) reported the
    threshold for changes in the electrical activity of the brain
    cortex, as measured by electro-encephalography, to be 0.05 mg/m3. 
    However, this result cannot be evaluated since experimental data
    were not provided.  The odour perception threshold for sensitive
    people was 0.07 mg/m3.

         In studies by Weber-Tschopp  et al. (1977), groups of human
    volunteer students of both sexes were exposed either for 60 min to
    acrolein at a concentration of 0.69 mg/m3 or to gradually
    increasing acrolein concentrations from 0 up to 1.37 mg/m3 over
    35 min followed by a 5-min exposure to 1.37 mg/m3.  In further
    experiments with side-stream cigarette smoke instead of pure
    acrolein vapour, it was noted that the effects of pure acrolein
    vapour were small compared to those produced by side-stream smoke
    with the same acrolein vapour concentration. It was concluded that
    acrolein was only to a minor extent responsible for the effects
    observed (Weber-Tschopp  et al., 1976). It must be noted, however,
    that a significant part of the acrolein in side-stream cigarette
    smoke may be associated with particulate matter (Ayer & Yeager,
    1982) and would not have been measured. This may have resulted in an
    underestimation of the acrolein concentration in the smoke.  Many of
    the studies considered in this section are old and the analytical
    techniques are often poorly described; the absolute figures reported
    may, therefore, be suspect.  Dermal exposure

         In an investigation into irritant dermatitis possibly caused by
    contaminants present in diallylglycol carbonate monomer, patch tests
    were conducted with acrolein in ethanol at concentrations of 0.01,
    0.1, 1, and 10% on groups of 8, 10, 48, and 20 volunteers,
    respectively. At 1%, six positive reactions were recorded, four
    cases of serious oedema with bullae and two of erythema.  At 10%,
    all subjects showed positive reactions with bullae, necrosis,
    inflammatory cell infiltrate, and papillary oedema (Lacroix  et al.,

        Table 11.  Thresholds for acute effects of acrolein on humans


    Concentration       Exposure                        Effect                                        Reference
      (mg/m3)         period (min)


        0.05                           changes in electrical activity of brain cortex              Sinkuvene (1970)
        0.07                           odour perception by most sensitive individuals              Sinkuvene (1970)
        0.13               5           no or medium subjective eye irritation                      Darley et al. (1960)a
        0.21               5           increased incidence of subjective eye irritation            Weber-Tschopp et al. (1977)b
        0.34              10           increased incidence of subjective nasal irritation          Weber-Tschopp et al. (1977)b
        0.34              30           time-related increase in eye-blink frequency                van Eick (1977)a
        0.39              10           increased incidence of subjective annoyance                 Weber-Tschopp et al. (1977)b
        0.48                           odour recognition                                           Leonardos et al. (1969)
        0.59              15           increase in eye-blink frequency                             Weber-Tschopp et al. (1977)b
        0.6               10           increase in sensitivity to light                            Plotnikova (1957)
        0.69              40           decrease in respiratory rate; increased incidence of        Weber-Tschopp et al. (1977)c
                                       subjective general irritation of eyes, nose, and neck
        0.69              10           increase in eye-blink frequency                             Weber-Tschopp et al. (1977)c
        1                  3           slight subjective conjunctival irritation                   Plotnikova (1957)
        1                  3           stinging sensation in nose                                  Plotnikova (1957)
        1.1                5           increased incidence of subjective eye irritation            Stephens et al. (1961)a
        1.1                5           increase in tear volume, pH,and lysozyme activity           Harada (1977)
        1.37              35           decrease in respiratory rate                                Weber-Tschopp et al. (1977)b
        1.5                3           pneumographic changes in rhythm and amplitude of            Plotnikova (1957)
                                       respiratory movements

    Table 11 (contd).


    Concentration       Exposure                                Effect                                Reference
      (mg/m3)         period (min)


        1.7                3           reflex action on optical chronaxy                           Plotnikova (1957)
        1.88                           extreme subjective irritation of all exposed mucosae;       Sim & Pattle (1957)
                                       lacrimation within 20 seconds
        2.80                           extreme subjective irritation of all exposed mucosae;       Sim & Pattle (1957)
                                       lacrimation within 5 seconds
        3                  5           medium to severe subjective eye irritation                  Darley et al. (1960)a
        4                2-3           acute subjective conjunctival and nasal irritation;         Plotnikova (1957)
                                       painful sensation in nasopharyngeal region

    a   exposure of eyes only
    b   exposure to gradually increasing concentrations up to 1.37 mg/m3
    c   exposure to a fixed concentration

    8.2  Long-term exposure

         No data are available on the long-term exposure of humans to


    9.1  Aquatic organisms

         A summary of acute aquatic toxicity data is presented in
    Table 12. In most of these studies, the amount of acrolein added was
    reported but the concentrations present were not measured.  In these
    cases, the actual concentrations may have been lower than the
    nominal ones in view of the volatility of the substance and its
    hydration rate (see section 4.2).

         One of the studies in Table 12 (Lorz  et al., 1979) is a
    comparatively detailed examination of the acute toxicity of acrolein
    to Coho salmon.  Within 144 h of exposure to 0.075 mg/litre or more,
    all fish died.  In surviving fish the activity of gill
    Na+,K+-ATPase (EC and the tolerance to subsequent
    sea-water exposure were not affected at concentrations up to
    0.05 mg/litre. A histological examination of the gills, kidneys, and
    liver at 0, 0.05, and 0.1 mg/litre revealed concentration-dependent
    adverse effects.

         A 3-generation 64-day test with the crustacean  Daphnia magna
    was conducted in a flow-through open system with well water at
    20 °C, a pH between 7.0 and 7.3, a dissolved oxygen concentration of
    7.5 mg/litre, and a water hardness of 35 mg CaCO3/litre.  The
    highest concentration that did not result in mortality was
    0.0169 mg/litre (acrolein concentrations were measured in this
    study).  Survival was reduced at levels of 0.0336 mg/litre or more,
    but the number of young per female was not affected even at the
    highest concentration tested, 0.0427 mg/litre (Macek  et al.,

         Macek  et al. (1976) also reported on a 60-day test with
    fathead minnow  (Pimephales promelas) in a flow-through open system
    with well water at 25 °C, a pH between 6.6 and 6.8, a dissolved
    oxygen concentration of 8.2 mg/litre, and a water hardness of 32 mg
    CaCO3/litre.  The highest concentration without adverse effects
    was 0.0114 mg/litre (acrolein concentrations were measured in this
    study). At 0.0417 mg/litre, there was increased mortality among
    offspring.  No adverse effects were found on survival and mortality
    of adults, number of spawnings and number of eggs per female, number
    of eggs per spawn, length of offspring, or hatchability.

         It is clear from Table 12 why acrolein is also used as an
    algicide, slimicide, and molluscicide.

        Table 12.  Acute aquatic toxicity of acrolein


    Organism    Species         Temperature  pH    Dissolved  Hardness   Stat/flow      Exposure  Parameterb        Concentration  Reference
                                   (°C)            O2 (mg/    (mg CaCO3  open/          period                      (mg/litre)
                                                   litre)     per litre)                closeda

    Fresh water

     alga       Enteromorpha       25                                    stat, closed    24 h     50% inhibition        1.8c       Fritz-
                intestinalis                                                                      of photosynthesis                Sheridan

     alga       Cladophora         25                                    stat, closed    24 h     50% inhibition        1.00c
                glomerata                                                                         of photosynthesis

     alga       Anabaena           25                                    stat, closed    24 h     50% inhibition        0.69c
                                                                                                  of photosynthesis

     bacterium  Proteus            37        7.0                         stat, closed     2 h     50% growth            0.02       Brown &
                vulgaris                                                                          reduction                        Fowler

     bacterium  Pseudomonas        25        7.0                         stat, closed    16 h     TT                    0.21       Bringmann
                putida                                                                                                             & Kuhn

     protozoan  Entosiphon         25        6.9                         stat, closed    72 h     TT                    0.85       Bringmann
                sulcatum                                                                                                           (1978)

     protozoan  Chilomonas         20        6.9                         stat, closed    48 h     TT                    1.7        Bringmann
                paramecium                                                                                                         et al.

    Table 12 (contd).


    Organism    Species         Temperature  pH    Dissolved  Hardness   Stat/flow      Exposure  Parameterb        Concentration  Reference
                                   (°C)            O2 (mg/    (mg CaCO3  open/          period                      (mg/litre)
                                                   litre)     per litre)                closeda

     protozoan  Uronema            25        6.8                         stat, closed    20 h     TT                    0.44       Bringmann
                parduczi                                                                                                           & Kuhn

     mollusc    snail             21-25                                  flow, open      48 h     99-100%               20-25      Unrau et
                (Bulinus                                                                          mortality                        al. (1965)d

     mollusc    snail                                                    stat, open       3 h     100% mortality       10          Ferguson
                (Biomphalaria                                                            24 h     10% mortality         1.25       et al.
                glabrata), eggs                                                                                                    (1961)

     mollusc    snail (Biomphalaria                                      stat, open      24 h     98% mortality        10          Ferguson
                glabrata), adults                                        24 h                     35% mortality         2.5        et al.

     crustacean water flea         20        7.0-  7.5        35         stat, open      48 h     LC50                  0.057      Macek et
                (Daphnia magna)              7.3                                                                                   al. (1976)

     crustacean water flea         22        7.0-             154        stat, closed    48 h     EC50f                 0.093      Randall &
                (Daphnia magna)              8.2                                                                                   Knopp (1980)

     crustacean water flea         22        7.4-  6-9        173        stat, closed    48 h     LC50                  0.083      LeBlanc
                (Daphnia magna)              9.4                                                                                   (1980)

     fish       harlequin fish     20        7.2              20         flow, open      48 h     LC50                  0.06       Alabaster
                (Rasbora                                                                                                           (1969)

    Table 12 (contd).


    Organism    Species         Temperature  pH    Dissolved  Hardness   Stat/flow      Exposure  Parameterb        Concentration  Reference
                                   (°C)            O2 (mg/    (mg CaCO3  open/          period                      (mg/litre)
                                                   litre)     per litre)                closeda

     fish       fathead minnow     25        6.6-  8.2        32         flow, open      144 h    LC50                  0.084      Macek et
                (Pimephales                  6.8                                                                                   al.
                promelas)                                                                                                          (1976)e

     fish       golden orfe        20        7-8   > 5        200-300    stat            48 h     LC50                  0.25 &     Juhnke &
                (Leuciscus idus                                                                                         2.5        Ludemann
                melanotus)                                                                                                         (1978)

     fish       goldfish           20        6-8   > 4        108        stat, open      24 h     LC50                < 0.08       Bridie
                (Carassius                                                                                                         et al.
                auratus)                                                                                                           (1979)c e

     fish       Bluegill          21-23      6.5-  10-        32-48      stat, closed    96 h     LC50                  0.09       Buccafusco
                sunfish                      7.9   0.3                                                                             et al.
                (Leopomis                                                                                                          (1981)

     fish       Coho salmon        10        7.4-  > 10       100        stat, open      96 h     LC50                  0.068      Lorz et al.
                (Oncorhynchus                7.6                                                                                   (1979)g

    Table 12 (contd).


    Organism    Species         Temperature  pH    Dissolved  Hardness   Stat/flow      Exposure  Parameterb        Concentration  Reference
                                   (°C)            O2 (mg/    (mg CaCO3  open/          period                      (mg/litre)
                                                   litre)     per litre)                closeda


     mollusc    common mussel      15                                    stat, closed     6 h     40% mortality         0.6        Rijstenbil
                (Mytilus edulis)                                                          6 h     70% mortality         1.0        & van Galen
                                                                                          8 h     70% detached          0.57       (1981)e h

    a  static or flow-through test, open or closed system
    b  TT = toxic threshold for inhibition of cell multiplication
    c  exposure to Magnacide-H (92% acrolein, 8% inert ingredients)
    d  field study, resurgence of snails was delayed by 8 to 12 months
    e  analysis for acrolein was reported
    f  the effect was complete immobilization
    g  static-renewal test
    h  static-renewal test (1.6% salinity)

    9.2  Terrestrial organisms

    9.2.1  Birds

         The LD50 for the adult starling  (Sturnus vulgaris) was
    reported to be > 100 mg/kg body weight. The birds were observed for
    7 days after dosing, but only two birds per dose were tested
    (Schafer, 1972).

    9.2.2  Plants

         Acrolein is used as biocide, particularly to control aquatic
    plants such as  Elodea canadensis, Vallisneria spiralis
    (ribbonweed), and  Potamogeton tricarinatus (floating pondweed). 
    In Australia, a maximum concentration of about 15 mg/litre over a
    period not exceeding a few hours has been imposed.  In the USA,
    acrolein is injected into larger channels over longer periods at low
    concentrations (approximately 0.1 mg/litre over 48 h) (Bowmer &
    Sainty, 1977). It has been shown that the dosage of acrolein
    required for control, as defined by the product of time and
    concentration required for 80% reduction in biomass, is independent
    of the separate values of concentration and time, provided that the
    concentration exceeds 0.1 mg/litre and the dosage exceeds 2 mg/litre
    per h.  In tank experiments, the minimum dosages required for 80%
    control of ribbonweed and floating pondweed were about 4 and
    26 mg/litre per h, respectively (Bowmer & Sainty, 1977).  The
    effective dosage (> 80% kill) for  Elodea canadensis was 8 to
    10 mg/litre per h (Van Overbeek  et al., 1959; Bowmer & Smith,
    1984).  Sublethal concentrations of acrolein stimulated the growth
    of  Elodea (Bowmer & Smith, 1984).

         Elongation of pollen tubes of lily seeds  (Lilium longiflorum)
    was inhibited completely after a 5-h exposure to acrolein vapour at
    a measured concentration of 0.91 mg/m3, a temperature of 28 °C,
    and a relative humidity of 60%.  A 10% inhibition was found after
    1 h (Masaru er al., 1976).

         The nature and extent of adverse effects on various crops grown
    in soil irrigated by acrolein-treated water have been investigated
    in two studies.  Acrolein concentrations varied between 15 and
    50 mg/litre of supply water.  Most furrow-irrigated crops, including
    beans, clover, corn, and millet, did not show any damage. 
    Significant damage to foliage was observed in cotton at acrolein
    concentrations of 25 mg/litre or more, but there was no evidence of
    chronic or residual phytotoxicity.  Slight damage to the foliage of
    cucumbers and tomatoes was observed at 40 mg/litre.  Vegetable
    seedlings in contact with treated water were damaged even at the
    lowest concentrations used (Unrau  et al., 1965; Ferguson  et al.,


    10.1  Evaluation of human health risks

    10.1.1  Exposure

         Exposure of the general population to acrolein occurs mainly
    via air. Exposure via water would only be significant in cases of
    ingestion of, or skin contact with, acrolein deliberately applied as
    a biocide to irrigation water. Oral exposure to acrolein may also
    occur via alcoholic beverages or heated foodstuffs (chapters 3 and

         In urban areas, average levels of up to 15 µg/m3 and maximum
    levels of up to 32 µg/m3 have been measured away from industrial
    sources. Near industries and close to the exhaust pipes of vehicles,
    engines, and combustion appliances, levels ten to one hundred times
    higher may occur.  Extremely high levels of acrolein in the mg/m3
    range can be found as a result of fires (section 5.2.1).

         Major indoor sources of acrolein are combustion appliances and
    tobacco smoking (section 3.2.4). Levels of acrolein in smoke from
    indoor open fires for cooking or heating purposes have not been
    reported.  Smoking one cigarette per m3 of room-space in 10-13 min
    has been shown to lead to acrolein vapour concentrations of
    450-840 µg/m3 (section 5.2.1). Recent occupational exposure levels
    of acrolein in the air at sites of its production or processing are
    not available.  Workplace levels of over 1000 µg/m3 have been
    reported in situations involving the heating of organic materials
    (section 5.3).

         In summary, the main source of exposure of the general
    population to acrolein is via tobacco smoke.  General environmental
    pollution by vehicle exhaust and the smoke of burning organic
    materials is the next most important source.

    10.1.2  Health effects

         Owing to the reactivity of acrolein, retention at the site of
    entry into the body, usually the respiratory tract, is high
    (section 6.1).  Primary pathological findings are limited
    principally to these sites (sections 7 and 8). Any acrolein absorbed
    is liable to react directly with protein and non-protein sulfhydryl
    groups or with primary and secondary amines such as those found in
    proteins and nucleic acids (sections 6.2 and 7.3). Acrolein may also
    be metabolized to mercapturic acids, acrylic acid, glycidaldehyde or
    glyceraldehyde (section 6.3). Evidence for the last three
    metabolites has only been obtained  in vitro.

         Acrolein is a cytotoxic agent (section 7.1.5) highly toxic to
    experimental animals and man following acute exposure via different
    routes (sections 7.1.1 and 8.1.1).  The vapour is very irritating to
    the eyes and the respiratory tract.  Liquid acrolein is a corrosive
    substance. The no-observed-adverse-effect level for irritant
    dermatitis from ethanolic acrolein was found to be 0.1% (section  The odour perception threshold for the most sensitive
    individuals is reported to be 0.07 mg/m3 (  Experiments
    with human volunteers show a lowest-observed-adverse-effect level of
    0.13 mg/m3, at which level eyes may become irritated after 5 min. 
    In addition to irritation of the eyes, changes in respiratory tract
    function are evident at or above 0.7 mg/m3 (40-min exposure)
    (section  At higher concentrations, degeneration of the
    respiratory epithelium and irritation of all exposed mucosa develop.
    Oedematous changes in the tracheal and bronchial mucosa and
    bronchial obstruction can be expected after very high exposure to
    acrolein vapour (section 8.1).

         There are no human toxicological data from long-term exposure
    to acrolein.  The toxicity from exposure to acrolein vapour has been
    relatively well investigated in several animal studies for exposure
    periods of up to 52 weeks (section 7.2).  Both respiratory tract
    function and histopathological effects have been observed at
    0.5-0.8 mg/m3 (continuous exposure).  Toxicological effects in the
    respiratory tract have been documented in most animal species
    exposed repeatedly to acrolein concentrations of 1.6-3.2 mg/m3 or
    more, and mortality has occurred following exposure to
    concentrations above 9 mg/m3.  There is limited evidence that
    acrolein can depress pulmonary host defenses in mice and rats.

         Acrolein can induce teratogenic and embryotoxic effects if
    administered directly into the amnion.  However, the fact that no
    effect was found in rabbits injected intravenously with 3 mg/kg
    suggests that human exposure to acrolein is unlikely to affect the
    developing embryo (section 7.5).

         Acrolein has been shown to interact with DNA and RNA  in vitro
    and to inhibit their synthesis both  in vivo and in vitro.  In
     vitro, it induces gene mutations in bacteria and fungi and sister
    chromatid exchanges in mammalian cells (section 7.6).  There is
    inadequate evidence to allow the mutagenic potential in humans to be
    assessed reliably.

         One long-term drinking-water study with rats (130 weeks) and
    two inhalation tests, one with hamsters (81 weeks) and the other
    with rats (40 or 70 weeks), failed to demonstrate carcinogenic or
    clear co-carcinogenic effects of acrolein (section 7.7).  Due to the
    shortcomings of the tests used, acrolein cannot be considered to
    have been adequately tested for carcinogenicity and no conclusions
    concerning its carcinogenicity are possible.

         The threshold levels of acrolein that cause irritation and
    health effects are 0.07 mg/m3 for odour perception, 0.13 mg/m3
    for eye irritation, 0.3 mg/m3 for nasal irritation and eye
    blinking,  and 0.7 mg/m3 for decreased respiratory rate.  Since
    the level of acrolein rarely exceeds 0.030-0.040 µg/m3 in polluted
    urban air or smoke-filled restaurants, acrolein alone is unlikely to
    reach annoyance or harmful levels in normal circumstances.  Provided
    that acrolein concentrations are maintained below 0.05 mg/m3, most
    of the population will be spared from any known annoyance or health
    effects.  However, in polluted urban areas and smoke-filled rooms,
    acrolein is present in combination with other irritating aldehydes,
    and control of acrolein alone is not sufficient to prevent annoyance
    or harmful effects.

    10.2  Evaluation of effects on the environment

         Acrolein is released into the environment during production of
    the compound itself and its derivatives, in processes involving
    incomplete combustion and/or pyrolysis of organic substances, by
    photochemical oxidation of specific air pollutants, and through
    biocidal use, spills, and waste disposal (chapter 3).

         Degradation in the atmosphere begins mainly by reaction with
    hydroxyl radicals.  The calculated atmospheric residence time is
    approximately one day (section 4.2).  Photolysis does not occur to a
    significant degree (section 4.2.1). In natural water, acrolein
    dissipates fairly rapidly as a result of catalysed hydration,
    reactions with organic material, and volatilization (sections 4.2
    and 4.3).  Acrolein has a low soil adsorption potential
    (section 4.1). Aerobic and anaerobic biodegradation of the compound
    has been reported, although its toxicity to microorganisms may
    prevent biodegradation (section 4.3.1).  Based on its physical and
    chemical properties, bioaccumulation would not be expected to occur
    (section 4.3.2). It can be concluded that acrolein is unlikely to
    persist in any environmental compartment.

         Acrolein is very toxic to aquatic organisms. Acute EC50 or
    LC50 values for various species range between 0.02 and
    2.5 mg/litre. The 60-day NOAEL for fish (fathead minnow) is
    0.0114 mg/litre (section 9.1).

         In view of the high toxicity of acrolein to aquatic organisms,
    the substance presents a risk to aquatic life at or near sites of
    industrial discharges, spills, and biocidal use.


    a)   Human exposure characteristics should be further evaluated.
         This applies to exposure due to environmental and  
         occupational air, as well as to intake from food and beverages.

    b)   These evaluations should include determinations of other  
         chemicals that occur with acrolein and that interact or have  
         biological effects similar to those due to acrolein exposure.

    c)   The most important target organ for airborne acrolein exposure
         is the respiratory system.  Therefore, further studies
         including epidemiological studies should focus on this system
         and particularly on the occupational environment.  Possible
         decreases in host resistance to respiratory infections should
         be investigated.

    d)   The uptake of acrolein in the different parts of the
         respiratory system should be examined further.  The metabolism
         and excretion of acrolein, as well as of its metabolites from
         the respiratory system, should be given high priority as there
         is an almost total lack of information about these processes.

    e)   The efficacy of sulfhydryl compounds, such as  N-acetylcysteine
         or 2-mercaptoethylsulfonic acid sodium salt (MESNA) as
         antidotes for acrolein poisoning should be evaluated.


         Evidence for the potential carcinogenicity of acrolein has been
    evaluated by the International Agency for Research on Cancer (IARC,
    1979, 1985, 1987).  The evidence for carcinogenicity was considered
    to be inadequate both in animals and in humans.  Thus no evaluation
    could be made of the carcinogenicity of acrolein to humans.

         Regulatory standards established by national bodies in various
    countries and the EEC are summarized in the data profile of the
    International Register of Potentially Toxic Chemicals (IRPTC, 1990)
    and are tabulated in the Health and Safety Guide for Acrolein (WHO,


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     situ with acidified 2,4-dinitrophenylhydrazine for sampling
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    TESTA, A. & JOIGNY, C. (1972) Dosage par chromatographie en phase
    gazeuse de l'acroléine et d'autres composés alpha,ß-insaturés de la
    phase gazeuse de la fumée de cigarette.  Ann. Serv. Exploit. ind.
    Tab. Allumettes - Div. Etud. Equip., 10: 67-81.

    BIAGINI, R.E. (1989) Comparative toxicity of allylamine and acrolein
    in cultured myocytes and fibroblasts from neonatal rat heart. 
    Toxicology, 56: 107-117.

    TREITMAN, R.D., BURGESS, W.A., & GOLD, A. (1980) Air contaminants
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    TURUK-PCHELINA, Z.F. (1960) [Acrolein releases into the air while
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    UMANO, K. & SHIBAMOTO, T. (1987) Analysis of headspace volatiles
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    US-NIOSH (1984)  NIOSH manual of analytical methods, 3rd ed.,
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    VAN OVERBEEK, J., HUGHES, W.J., & BLONDEAU, R. (1959) Acrolein for
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         L'acroléine est un liquide volatil extrêmement inflammable dont
    l'odeur, âcre et suffocante, est très désagréable. C'est un composé
    très réactif.

         En 1975, on estime que la production mondiale d'acroléine en
    tant que telle était de 59 000 tonnes. On en produit et consomme
    encore davantage comme intermédiaire pour la synthèse de l'acide
    acrylique et de ses esters.

         On dispose d'un certain nombre de méthodes d'analyse pour la
    recherche et le dosage de l'acroléine dans divers milieux. On a fait
    état de limites inférieures de détection de l'ordre de 0,1 µg/m3
    dans l'air (chromatographie en phase gazeuse/spectrométrie de
    masse), de 0,1 µg/l dans l'eau (chromatographie liquide à haute
    pression), de 2,8 µg/litre dans les milieux biologiques
    (fluorimétrie), de 590 µg/kg dans le poisson (chromatographie en
    phase gazeuse/spectrométrie de masse) et de 1,4 µg/m3 dans les gaz
    d'échappement (chromatographie liquide à haute pression).

         On a trouvé de l'acroléine dans certains produits d'origine
    végétale et animale et notamment dans des denrées alimentaires et
    des boissons. L'acroléine est utilisée principalement comme
    intermédiaire en synthèse organique, mais également comme produit
    biocide en milieu aquatique.

         Des émissions d'acroléine peuvent se produire sur les lieux de
    production ou d'utilisation. Elles peuvent être importantes dans
    l'air à la suite de la combustion ou de la pyrolyse incomplète de
    produits organiques tels que combustibles, polymères de synthèse,
    dans certains aliments et le tabac. L'acroléine peut représenter
    jusqu'à 3-10 % des aldéhydes totaux présents dans les gaz
    d'échappement des véhicules à moteur. La consommation d'une
    cigarette fournit de 3 à 228 µg d'acroléine. L'acroléine est un
    produit d'oxydation photochimique de certains polluants organiques
    de l'atmosphère.

         La population générale est essentiellement exposée par
    l'intermédiaire de l'air. Une exposition peut également se produire
    par voie orale par suite de la consommation de boissons alcoolisées
    ou de denrées alimentaires chauffées.

         On a mesuré dans l'air des villes des concentrations moyennes
    d'acroléine atteignant environ 15 µg/m3 avec des maxima allant
    jusqu'à 32 µg/m3. A proximité d'installations industrielles et de
    pots d'échappement, des concentrations dix à cent fois plus élevées
    sont possibles. Les incendies peuvent donner naissance à des teneurs
    très élevées d'acroléine, de l'ordre du mg/m3 d'air.  A
    l'intérieur des habitations, on a observé que la consommation d'une
    cigarette par m3 d'air dans un local en l'espace de 10 à

    13 minutes produisait des concentrations en vapeurs d'acroléine de
    l'ordre de 450 à 840 µg/m3. Sur les lieux de travail, on a signalé
    des teneurs dépassant 100 µg/m3 dans des cas où l'on élevait la
    température de certains produits organiques, par exemple lors du
    chauffage ou du soudage de ces substances.

         Dans l'atmosphère, l'acroléine est dégradée par réaction avec
    les radicaux hydroxyles. Sa durée de séjour dans l'atmosphère est de
    l'ordre d'une journée. Dans les eaux de surface, l'acroléine se
    dissipe en quelques jours. Elle est faiblement adsorbée aux
    particules du sol. On a fait état de dégradation aérobie et
    anaérobie, encore que la toxicité du composé pour les
    micro-organismes puisse faire obstacle à sa biodégradation. Compte
    tenu des propriétés physiques et chimiques de l'acroléine, il ne
    semble pas que cette substance ait une tendance à la

         L'acroléine est extrêmement toxique pour les organismes
    aquatiques. Pour les bactéries, les algues, les crustacés et les
    poissons, sa toxicité aiguë, estimée d'après les valeurs de la CE50
    et de la CL50, se situe entre 0,02 et 2,5 mg/litre, les bactéries
    étant l'espèce la plus sensible. Pour le poisson, on a fixé à
    0,0114 mg/litre la dose sans effet nocif observable à 60 jours.
    L'acroléine détruit efficacement les végétaux aquatiques à des doses
    comprises entre 4 et 26 mg/litre.h. A partir de 15 mg/litre, on
    observe des effets nocifs sur les cultures irriguées au moyen d'eau
    traitée à l'acroléine.

         Chez l'homme et l'animal, l'acroléine reste confinée sur son
    site d'exposition en raison de sa réactivité et les observations
    pathologiques sont également limitées à ce site. Chez des chiens
    exposés à des doses de 400 à 600 mg/m3, on a observé un taux de
    rétention de 80 à 85 % au niveau des voies respiratoires.
    L'acroléine réagit directement sur les groupements sulfhydryles
    protéiques et non protéiques ainsi que sur les amines primaires et
    secondaires. Elle peut également être métabolisée en acide
    mercapturique, en acide acrylique, en glycidaldéhyde ou en
    glycéraldéhyde. Les trois derniers métabolites n'ont été observés
    qu' in vitro.

         L'acroléine est un agent cytotoxique. Sa cytotoxicité s'observe
     in vitro dès 0,1 mg/litre. Elle est extrêmement toxique pour les
    animaux de laboratoire et l'homme, à la suite d'une seule exposition
    quelle qu'en soit la voie. Sa vapeur est irritante pour l'oeil et
    les muqueuses respiratoires. Le liquide est corrosif et on a
    constaté qu'en solution éthanolique le seuil d'apparition d'une
    dermatite d'irritation était de 0,1%. L'expérimentation sur des
    volontaires humains exposés à des vapeurs d'acroléine a permis de
    fixer à 0,13 mg/m3 la dose la plus faible produisant des effets
    nocifs observables; à cette dose, une irritation des yeux se produit
    en l'espace de cinq minutes. En outre, les effets au niveau des

    voies respiratoires deviennent évidents à partir de 0,7 mg/m3. Une
    seule exposition à des doses plus élevées entraîne une
    dégénérescence de l'épithélium respiratoire, des séquelles
    inflammatoires et une perturbation de la fonction respiratoire.

         On a étudié sur des rats, des chiens, des cobayes et des singes
    les effets toxicologiques de l'inhalation continue d'acroléine à des
    concentrations de 0,5 à 4,1 mg/m3. Des effets histopathologiques
    et des effets sur la fonction respiratoire ont été observés chez les
    animaux exposés à des teneurs supérieures ou égales à 0,5 mg/m3
    pendant 90 jours.

         On a étudié sur divers animaux de laboratoire les effets
    toxicologiques d'expositions répétées par la voie respiratoire à des
    vapeurs d'acroléine, à des concentrations allant de 0,39 mg/m3 à
    11,2 mg/m3. La durée de l'exposition allait de cinq jours à
    52 semaines. En général, on a fait état chez la plupart des espèces
    exposées huit heures par jour à des concentrations de 1,6 mg/m3 ou
    davantage, d'une réduction du gain de poids, d'une diminution de la
    fonction respiratoire et de modifications pathologiques au niveau du
    nez, des voies respiratoires supérieures et des poumons. Parmi les
    modifications anatomopathologiques figuraient une inflammation, une
    métaplasie et une hyperplasie des voies respiratoires. On a observé
    une mortalité importante après expositions répétées à des vapeurs
    d'acroléine à des concentrations dépassant 9,07 mg/m3. Chez
    l'animal d'expérience, on a montré que l'acroléine provoquait une
    déplétion du glutathion tissulaire  in vivo et une inhibition des
    enzymes  in vitro par réaction sur les groupements sulfhydryles au
    niveau des sites actifs. Il existe quelques données selon lesquelles
    l'acroléine est susceptible d'amoindrir les défenses pulmonaires de
    l'hôte chez la souris et le rat.

         L'acroléine peut produire des effets tératogènes et
    embryotoxiques lorsqu'on l'introduit directement dans l'amnios.
    Toutefois, l'absence d'effets chez des lapins à qui elle avait été
    injectée par voie intraveineuse à la dose de 3 mg/kg incite à penser
    que l'exposition de l'homme à l'acroléine ne devrait pas avoir
    d'effet nocif sur le développement de l'embryon.

         On a montré que l'acroléine interagissait avec les acides
    nucléiques  in vitro et en inhibait la synthèse tant  in vitro
    qu' in vivo. Sans avoir besoin d'être activée, elle produit des
    mutations géniques chez les bactéries et les champignons et induit
    des échanges entre chromatides soeurs dans les cellules
    mammaliennes. Dans tous les cas, ces effets se sont produits dans un
    intervalle de dose extrêmement limité qui était fonction de la
    réactivité, de la volatilité et de la cytotoxicité de l'acroléine.
    Une épreuve de mutation létale dominante chez la souris a donné des
    résultats négatifs. Les données disponibles montrent que l'acroléine
    est faiblement mutagène pour certains champignons et bactéries et
    certaines cultures de cellules mammaliennes.

         Des hamsters ont été exposés pendant 52 semaines à des vapeurs
    d'acroléine à la dose de 9,2 mg/m3, 7 heures par jour et 5 jours
    par semaine, puis ont été placés en observation pendant les 29
    semaines suivantes; aucune tumeur n'a été observée. En exposant ces
    hamsters dans les mêmes conditions à des vapeurs d'acroléine et
    pendant la même durée avec, en outre, des doses intra-trachéennes
    hebdomadaires de benzo[a]pyrène ou des doses sous-cutanées une fois
    toutes les trois semaines de diéthylnitrosamine, on n'a pas non plus
    observé d'effets co-cancérogènes bien nets attribuables à
    l'acroléine. Des rats exposés par voie orale à de l'acroléine dans
    leur eau de boisson à des doses comprises entre 5 et 50 mg/kg par kg
    de poids corporel (quotidiennement, cinq jours par semaine pendant
    100 à 124 semaines) n'ont pas présenté de tumeur. En raison du
    caractère limité de toutes ces épreuves, on estime que les données
    qui permettraient d'évaluer la cancérogénicité de l'acroléine chez
    l'animal d'expérience sont encore insuffisantes. De ce fait, il est
    impossible pour l'instant d'évaluer la cancérogénicité de
    l'acroléine pour l'homme.

         Les différents seuils de concentration auxquels apparaissent
    les différents effets de l'acroléine sont les suivants : perception
    d'une odeur, 0,007 mg/m3, irritation oculaire, 0,3 mg/m3,
    irritation du nez et clignement des yeux, 0,03 mg/m3, réduction de
    la fréquence respiratoire, 0,7 mg/m3. Comme la concentration de
    l'acroléine dépasse rarement 0,03 mg/m3 dans l'air des villes,
    elle n'est pas susceptible de constituer une nuisance dans les
    circonstances normales.

         Du fait de sa forte toxicité pour les organismes aquatiques,
    l'acroléine présente un danger pour la faune et la flore aquatique à
    proximité ou sur les sites de décharge de déchets industriels, en
    cas de déversements et là où l'on utilise ce produit comme biocide.

    1.  RESUMEN

         La acroleína es un líquido volátil, sumamente inflamable, con
    un olor pungente, asfixiante y desagradable.  Se trata de un
    compuesto muy reactivo.

         La producción mundial de acroleína aislada se calculó en 59 000
    toneladas en 1975.  Se produce y consume una cantidad aún mayor de
    acroleína como intermediaria en la síntesis de ácido acrílico y sus

         Se dispone de métodos analíticos para determinar la acroleína
    presente en diversos medios.  Los límites mínimos de detección que
    se han comunicado son 0,1 µg/m3 de aire (cromatografía
    gaseosa/spectrometría de masas), 0,1 µg/litro de agua (cromatografía
    líquida a alta presión), 2,8 µg/litro de medio biológico
    (fluorimetría), 590 µg/kg en peces (cromatografía
    gaseosa/espectrometría de masas), y 1,4 µg/m3 de gases de escape
    (cromatografía líquida a alta presión).

         La acroleína se ha detectado en algunos vegetales y animales,
    inclusive en alimentos y bebidas.  La sustancia se usa
    principalmente como intermediaria en la síntesis química aunque
    también como biocida acuático.

         Pueden producirse emisiones de acroleína en sus lugares de
    producción o de uso.  Las emisiones importantes a la atmósfera se
    deben a la combustión incompleta o la pirólisis de materiales
    orgánicos como ser combustibles, polímeros sintéticos, alimentos y
    tabaco.  La acroleína puede representar el 3-10% de los aldehídos
    totales presentes en los escapes de automóviles.  El humo de un
    cigarrillo libera 3-228 µg de acroleína.  La acroleína es uno de los
    productos de la oxidación fotoquímica de ciertos contaminantes
    orgánicos de la atmósfera.

         La exposición de la población general se produce principalmente
    por el aire.  La exposición por vía oral puede producirse por el
    consumo de bebidas alcohólicas o alimentos calentados.

         En la atmósfera urbana se han medido niveles promedio de
    acroleína de hasta unos 15 µg/m3 y niveles máximos de hasta
    32 µg/m3.  En las cercanías de las industrias y junto a los caños
    de escape pueden registrarse niveles entre 10 y 100 veces
    superiores.  Como resultado de incendios pueden hallarse niveles
    sumamente elevados en el aire, del orden de mg/m3.  En el aire
    cerrado de interiores, el consumo de un cigarrillo por m3 de
    volumen de la habitación produjo en 10-13 minutos concentraciones de
    vapor de acroleína de 450-840 µg/m3.  En el medio ambiente laboral
    se han detectado niveles de más de 1000 µg/m3 en situaciones que
    entrañaban aumento de temperatura de materiales orgánicos, por
    ejemplo durante la soldadura o el calentamiento.

         La acroleína se degrada en la atmósfera por reacción con
    radicales hidroxilo.  El tiempo de persistencia en la atmósfera es
    de aproximadamente un día.  En aguas de superficie, la acroleína se
    disipa en pocos días.  Tiene un bajo potencial de adsorción en el
    suelo.  Se ha observado su degradación en condiciones aerobias y
    anaerobias, si bien la toxicidad del compuesto para los
    microorganismos puede impedir la biodegradación.  En vista de sus
    propiedades físicas y químicas, es improbable que se produzca
    bioacumulación de acroleína.

         La acroleína es sumamente tóxica para los organismos acuáticos. 
    Los valores de la CE50 y la CL50 correspondientes a bacterias,
    algas, crustáceos y peces se encuentran entre 0,02 y 2,5 mg/litro,
    siendo las bacterias los organismos más sensibles.  En peces se ha
    determinado que el nivel sin observación de efectos adversos (NOAEL)
    a 60 días es de 0,0114 mg/litro.  Se ha conseguido combatir
    eficazmente los vegetales acuáticos con dosis de acroleína
    comprendidas entre 4 y 26 mg/litro.h.  Se han observado efectos
    adversos en cultivos que crecen en suelos irrigados con agua tratada
    con acroleína en concentraciones de 15 mg/litro o más.

         En el animale y en el ser humano la reactividad de la acroleína
    limita efectivamente la sustancia al lugar de exposición; los
    hallazgos patológicos se limitan asimismo a esos lugares.  En el
    tracto respiratorio de perros expuestos a 400-600 mg/m3 se
    encontró una retención del 80-85% de acroleína.  La acroleína
    reacciona directamente con los grupos sulfhidrilo contenidos en
    radicales proteicos o no proteicos y con aminas primarias y
    secundarias. También puede ser metabolizado a ácidos mercaptúricos,
    ácido acrílico, glicidaldehído o gliceraldehído.  Estos tres últimos
    metabolitos sólo se han encontrado  in vitro.

         La acroleína es un agente citotóxico.  Se ha observado
    citotoxicidad  in vitro con niveles de solamente 0,1 mg/litro.  La
    sustancia es sumamente tóxica para los animales de experimentación y
    el ser humano tras una exposición única por diferentes vías.  El
    vapor es irritante para los ojos y el tracto respiratorio.  En
    estado líquido es corrosiva.  Con respecto a la dermatitis
    irritante, se encontró que el NOAEL de la acroleína etanólica era de
    0,1%.  Los experimentos con voluntarios humanos expuestos a vapores
    de acroleína mostraron un nivel mínimo de observación de efectos
    (LOAEL) de 0,13 mg/m3, dosis con la que los ojos pueden irritarse
    al cabo de cinco minutos.  Además, se observan efectos en el tracto
    respiratorio a partir de 0,7 mg/m3.  Con exposiciones aisladas a
    niveles más altos, aparecen: degeneración del epitelio respiratorio,
    secuelas inflamatorias y trastorno de la función respiratoria.

         Los efectos toxicológicos de la exposición por inhalación
    continua de concentraciones comprendidas entre 0,5 y 4,1 mg/m3 se
    han estudiado en la rata, el perro, el cobayo y el mono.  Se
    observaron efectos sobre la función respiratoria y trastornos

    histopatológicos cuando se expuso a los animales a niveles de
    acroleína de 0,5 mg/m3 o más, durante 90 días.

         Los efectos toxicológicos de la inhalación repetida de vapores
    de acroleína en concentraciones comprendidas entre 0,39 mg/m3 y
    11,2 mg/m3 se han estudiado en diversos animales de laboratorio. 
    Las duraciones de la exposición variaron entre 5 días y hasta 52
    semanas.  En general, se han documentado: reducción de la
    adquisición de peso corporal, disminución de la función pulmonar y
    cambios patológicos en la nariz, las vías aéreas superiores y los
    pulmones en la mayoría de las especies expuestas a concentraciones
    de 1,6 mg/m3 o más, durante 8 h/día.  Entre los cambios
    patológicos se observaron inflamación, metaplasia e hiperplasia del
    tracto respiratorio.  Se ha observado un nivel significativo de
    mortalidad tras la exposición repetida a concentraciones de vapor de
    acroleína superiores a 9,07 mg/m3.  En animales de
    experimentación, se ha demostrado que la acroleína agota el
    glutatión tisular y que  in vitro inhibe enzimas reaccionando con
    los grupos sulfhidrilo de los sitios activos.  Hay limitada
    evidencia de que la acroleína pueda deprimir las defensas pulmonares
    en el ratón y la rata.

         La acroleína puede inducir efectos teratogénicos y
    embriotóxicos si se administra directamente en el amnios.  No
    obstante, el hecho de que no se observaran efectos en ratones a los
    que se inyectó 3 mg/kg por vía intravenosa sugiere que la exposición
    humana a la acroleína tiene pocas probabilidades de afectar al
    embrión en desarrollo.

         Se ha demostrado que la acroleína interacciona con los ácidos
    nucleicos  in vitro y que inhibe su síntesis tanto  in vitro como
    in vivo. Sin activación, indujo mutaciones génicas en bacterias y
    hongos y provocó intercambios de cromátidas hermanas en células de
    mamíferos.  En todos los casos esos efectos se produjeron en un
    margen muy reducido de concentraciones, limitado por la reactividad,
    la volatilidad y la citotoxicidad de la acroleína.  Un ensayo de
    letalidad dominante en ratones dio resultado negativo.  Los datos
    disponibles muestran que la acroleína es un mutágeno débil para
    ciertas bacterias, hongos y cultivo celular de mamífero.

         No se encontraron tumores en hámsters expuestos durante 52
    semanas a vapores de acroleína con una concentración de 9,2 mg/m3
    durante 7 h/día, 5 días a la semana, y observados durante 29 semanas
    más.  Cuando se expusieron hámsters a vapores de acroleína en las
    mismas condiciones durante 52 semanas y, además, a dosis
    intratraqueales de benzo[a]pireno semanalmente o a dosis subcutáneas
    de dietilnitrosamina una vez cada tres semanas, no se observó una
    acción cocarcinogénica clara de la acroleína.  La exposición de
    ratas por vía oral a la acroleína en el agua de bebida, en dosis
    comprendidas entre 5 y 50 mg/kg de peso corporal al día
    (5 días/semana durante 104-124 semanas) no indujo tumores.  Dado el

    carácter limitado de todos esos ensayos, se considera que no se
    dispone de datos suficientes para determinar la carcinogenicidad de
    la acroleína en los animales de experimentación.  En consecuencia,
    se considera asimismo imposible evaluar la carcinogenicidad de la
    acroleína para el ser humano.

         Los umbrales de acroleína que causan irritación y efectos en la
    salud son 0,07 mg/m3 en el caso de la percepción del olor,
    0,13 mg/m3 en la irritación ocular, 0,3 mg/m3 en la irritación
    nasal y el parpadeo, y 0,7 mg/m3 en la disminución del ritmo
    respiratorio.  Puesto que el nivel de acroleína raras veces supera
    los 0,03 mg/m3 en el aire urbano, es poco probable que alcance
    niveles molestos o nocivos en circunstancias normales.

         En vista de la elevada toxicidad de la acroleína para los
    organismos acuáticos, la sustancia representa un riesgo para la vida
    acuática en las proximidades de las zonas donde se producen vertidos
    y escapes industriales, y en los lugares donde se usa como biocida.

    See Also:
       Toxicological Abbreviations
       Acrolein (HSG 67, 1991)
       Acrolein (ICSC)
       Acrolein (CICADS 43, 2002)
       Acrolein (IARC Summary & Evaluation, Volume 63, 1995)