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

    First draft prepared by Mrs. J. de Fouw, National Institute of Public
    Health and Enviromental Protection, Bilthoven, Netherlands

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

    World Health Organization
    Geneva, 1995

         The International Programme on Chemical Safety (IPCS) is a joint
    venture of the United Nations Environment Programme, the International
    Labour Organisation, and the World Health Organization. The main
    objective of the IPCS is to carry out and disseminate evaluations of
    the effects of chemicals on human health and the quality of the
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    of the biological action of chemicals.

    WHO Library Cataloguing in Publication Data


    (Environmental health criteria ; 167)

    1.Acetadehyde - adverse effects  2.Enviromental exposure   I.Series

    ISBN 92 4 157167 5                 (NLM Classification: QU 99)
    ISSN 0250-863X

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    1.   SUMMARY

         1.1   Identity, physical and chemical properties,
               and analytical methods
         1.2   Sources of human and environmental exposure
         1.3   Environmental transport, distribution, and
         1.4   Environmental levels and human exposure
         1.5   Kinetics and metabolism
               1.5.1   Absorption, distribution, and elimination
               1.5.2   Metabolism
               1.5.3   Reaction with other components
         1.6   Effects on organisms in the environment
               1.6.1   Aquatic organisms
               1.6.2   Terrestrial organisms
         1.7   Effects on experimental animals and  in vitro test
               1.7.1   Single exposure
               1.7.2   Short- and long-term exposures
               1.7.3   Reproduction, embryotoxicity, and
               1.7.4   Mutagenicity and related end-points
               1.7.5   Carcinogenicity
               1.7.6   Special studies
         1.8   Effects on humans
         1.9   Evaluation of human health risks and effects on the


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


         3.1   Natural occurrence
         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
         4.3   Biodegradation


         5.1   Environmental levels
               5.1.1   Air
               5.1.2   Water
               5.1.3   Soil
               5.1.4   Food
               5.1.5   Cigarette smoke
         5.2   General population exposure
         5.3   Occupational exposure


         6.1   Absorption
         6.2   Distribution
               6.2.1   Animal studies
                Distribution after inhalation
                Distribution to the embryo and
                Distribution to the brain
               6.2.2   Human studies
         6.3   Metabolism
               6.3.1   Animal studies
                Respiratory tract
                Testes and ovaries
                Embryonic tissue
                Metabolism during pregnancy
               6.3.2   Human studies

         6.4   Elimination
         6.5   Reaction with cellular macromolecules
               6.5.1   Proteins
               6.5.2   Nucleic acids


         7.1   Aquatic organisms
         7.2   Terrestrial organisms


         8.1   Single exposure
               8.1.1   LD50 and LC50 values
         8.2   Short-term exposure
               8.2.1   Oral
               8.2.2   Inhalation
               8.2.3   Dermal
               8.2.4   Parenteral
         8.3   Skin and eye irritation; sensitization
         8.4   Long-term exposure
               8.4.1   Oral
               8.4.2   Inhalation
         8.5   Reproductive and developmental toxicity
         8.6   Mutagenicity and related end-points
               8.6.1   Bacteria
               8.6.2   Non-mammalian eukaryotic systems
                Gene mutation assays
                Chromosome alterations
               8.6.3   Cultured mammalian cells
                Gene mutation assays
                Chromosome alterations and sister
                                 chromatid exchange
               8.6.4    In vivo assays
                Somatic cells
                Germ cells
               8.6.5   Other assays
                DNA single-strand breaks
                DNA cross-linking
               8.6.6   Cell transformation
         8.7   Carcinogenicity bioassays
               8.7.1   Inhalation exposure
               8.7.2   Co-carcinogenicity and promotion studies
         8.8   Neurological effects
         8.9   Immunological effects
               8.9.1   Direct effects on immune cells
               8.9.2   Generation of antibodies reacting with
                       acetaldehyde-modified proteins
               8.9.3   Related immunological effects
         8.10  Biochemical effects


         9.1   General population exposure
         9.2   Occupational exposure
               9.2.1   General observations
               9.2.2   Clinical studies
               9.2.3   Epidemiological studies
         9.3   Effects of endogenous acetaldehyde
               9.3.1   Effects of ethanol possibly attributable to
                       acetaldehyde or acetaldehyde metabolism


         10.1  Evaluation of human health risks
               10.1.1  Exposure
               10.1.2  Health effects
               10.1.3  Approaches to risk assessment
         10.2  Evaluation of effects on the environment






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

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         A detailed data profile and a legal file can be obtained from the
    International Register of Potentially Toxic Chemicals, Case postale
    356, 1219 Châtelaine, Geneva, Switzerland (Telephone No. 9799111).

                                      *     *     *

         This publication was made possible by grant number
    5 U01 ES02617-15 from the National Institute of Environmental Health
    Sciences, National Institutes of Health, USA, and by financial support
    from the European Commission.

    Environmental Health Criteria



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    FIGURE 1



    Mrs I. Arts, Department of Biological Toxicology, TNO Nutrition and
       Food Research, Zeist, The Netherlands

    Dr R.E. Barry, Faculty of Medicine, University of Bristol, Bristol
       Royal Infirmary, Bristol, United Kingdom

    Professor D. Beritic-Stahuljak, Andrija œtampar School of Public
       Health, Faculty of Medicine, University of Zagreb, Zagreb, Croatia

    Dr Sai Mei Hou, Karolinska Institute, Huddinge, Sweden

    Dr M.E. Meek, Environmental Health Directorate, Priority Substances
       Section, Health & Welfare Canada, Tunney's Pasture, Ottawa, Canada

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

    Professor G. Obe, University of Essen, Essen, Germany

    Professor T.V.N. Persaud, Department of Anatomy, Faculty of   
       Medicine, University of Manitoba, Winnipeg, Manitoba, Canada

    Mr D. Renshaw, Department of Health, Elephant & Castle, London, United

    Dr A. Smith, Health and Safety Executive, Toxicology Unit, Bootle,
       Merseyside, United Kingdom  (Co-rapporteur)

    Professor A. Watanabe, Toyama Medical and Pharmaceutical University,
       Faculty of Medicine, Toyama, Japan

    Dr S. Worrall, Department of Biochemistry, University of Queensland,
       Brisbane, Queensland, Australia

     Representatives from other organizations

    Dr V. Krutovskikh, Programme of Multistage Carcinogenesis,
       International Agency for Research on Cancer, Lyon, France


    Mrs J. de Fouw, National Institute of Public Health and Environmental
       Protection, Bilthoven, The Netherlands

    Professor F. Valic, IPCS Consultant, World Health Organization,
       Geneva, Switzerland, also Vice-Rector, University of Zagreb,
       Zagreb, Croatia  (Responsible Officer and Secretary)


         A WHO Task Group on Environmental Health Criteria for
    Acetaldehyde met in Geneva from 6 to 10 December 1993. Professor F.
    Valic opened the meeting on behalf of the three cooperating
    organizations of the IPCS (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 acetaldehyde.

         The first draft of this monograph was prepared by Mrs J. de Fouw,
    National Institute of Public Health and Environmental Protection,
    Bilthoven, The Netherlands.

         Professor F. Valic was responsible for the overall scientific
    content of the monograph and for the organization of the meeting, and
    Mrs M.O. Head of Oxford for the technical editing of the monograph.

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


         This monograph will deal mainly with the effects of direct
    exposure to acetaldehyde.  However, it should be borne in mind that
    for most people exposure to acetaldehyde will occur through the
    consumption of alcoholic beverages (IARC, 1988).  These beverages
    contain ethanol, which is metabolized to acetaldehyde by alcohol
    dehydrogenase (ADH).  ADH activity has been detected in nearly every
    tissue including liver, kidney, muscle, intestine, ovary, and testes
    (Buehler et al., 1983; Agarwal & Goedde, 1990).

         However, data concerning metabolically formed acetaldehyde will
    only be considered when no data are available on direct exposure.

         The accurate determination of acetaldehyde in body fluid and
    tissue samples is relatively difficult.  Only the most recent
    techniques take into account artifactual acetaldehyde formation in
    biological samples, especially those containing ethanol (Eriksson &
    Fukunaga 1993).  As values for concentrations of acetaldehyde given in
    older references may well have been overestimates, absolute values are
    only given when necessary.

    1.  SUMMARY

    1.1  Identity, physical and chemical properties, and analytical

         Acetaldehyde is a colourless, volatile liquid with a pungent
    suffocating odour.  The reported odour threshold is 0.09 mg/m3. 
    Acetaldehyde is a highly flammable and reactive compound that is
    miscible in water and most common solvents.

         Analytical methods are available for the detection of
    acetaldehyde in air (including breath) and water.  The principal
    method is based on the reaction of acetaldehyde with
    2,4-dinitrophenylhydrazine and subsequent analysis of the hydrazone
    derivatives by high pressure liquid chromatography or gas

    1.2  Sources of human and environmental exposure

         Acetaldehyde is a metabolic intermediate in humans and higher
    plants and a product of alcohol fermentation.  It has been identified
    in food, beverages, and cigarette smoke.  It is also present in
    vehicle exhaust and in wastes from various industries.  Degradation of
    hydrocarbons, sewage, and solid biological wastes produces
    acetaldehyde, as well as the open burning and incineration of gas,
    fuel oil, and coal.

         More than 80% of the acetaldehyde used commercially is produced
    by the liquid-phase oxidation of ethylene with a catalytic solution of
    palladium and copper chlorides.  Production in Japan was 323 thousand
    tonnes in 1981. In the USA, production was 281 thousand tonnes in 1982
    while in Western Europe it was 706 thousand tonnes in 1983.  Most
    acetaldehyde produced commercially is used in the production of acetic
    acid.  It is also used in flavourings and foods.

         The annual emission of acetaldehyde from all sources in the USA
    is estimated to be 12.2 million kg.

    1.3  Environmental transport, distribution, and transformation

         Because of its high reactivity, intercompartmental transport of
    acetaldehyde is expected to be limited.  Some transfer of acetaldehyde
    to air from water and soil is expected because of the high vapour
    pressure and low sorption coefficient.

         It is suggested that the photo-induced atmospheric removal of
    acetaldehyde occurs predominantly via radical formation. Photolysis is
    expected to contribute another substantial fraction to the removal
    process.  Both processes cause a reported daily loss of about 80% of
    atmospheric acetaldehyde emissions.  Reported half-lives of
    acetaldehyde in water and air are 1.9 h and 10-60 h, respectively.

         Acetaldehyde is readily biodegradable.

    1.4  Environmental levels and human exposure

         Levels of acetaldehyde in ambient air generally average
    5 µg/m3.  Concentrations in water are generally less than
    0.1 µg/litre.  Analysis of a wide range of foodstuffs in the
    Netherlands showed that concentrations, generally less than 1 mg/kg,
    occasionally ranged up to several 100 mg/kg, particularly in some
    fruit juices and vinegar.

         By far, the main source of exposure to acetaldehyde for the
    majority of the general population is through the metabolism of
    alcohol.  Cigarette smoke is also a significant source of exposure. 
    With respect to other media, the general population is exposed to
    acetaldehyde principally from food and beverages, and, to a lesser
    extent, from air.  The contribution from drinking-water is negligible.

         Available data are inadequate to determine the extent of exposure
    to acetaldehyde in the workplace.  Workers may be exposed in some
    manufacturing industries and during alcohol fermentation, where the
    principal route of exposure is most likely inhalation with possible
    dermal contact.

    1.5  Kinetics and metabolism

    1.5.1  Absorption, distribution, and elimination

         Available studies on toxicity indicate that acetaldehyde is
    absorbed through the lungs and gastrointestinal tract; however, no
    adequate quantitative studies have been identified.  Absorption
    through the skin is probable.

         Following inhalation by rats, acetaldehyde is distributed to the
    blood, liver, kidney, spleen, heart, and other muscle tissues.  Low
    levels were detected in embryos after maternal intraperitoneal (ip)
    injection of acetaldehyde (mouse) and following maternal exposure to
    ethanol (mouse and rat).  Potential production of acetaldehyde has
    also been observed in rat fetuses and in the human placenta,
     in vitro.

         Distribution of acetaldehyde to brain interstitial fluid, but not
    to brain cells, has been demonstrated following ip injection of
    ethanol.  A high affinity, low Km ALDHa may be important in
    maintaining low levels of acetaldehyde in the brain during the
    metabolism of ethanol.

         Acetaldehyde is taken up by red blood cells and, following
    ethanol consumption in humans and in baboons,  in vivo,
    intracellular levels can be 10 times higher than plasma levels.

         Following oral administration, virtually no unchanged
    acetaldehyde is excreted in the urine.

    1.5.2  Metabolism

         The major pathway for the metabolism of acetaldehyde is by
    oxidation to acetate under the influence of NADb-dependent ALDH. 
    Acetate enters the citric acid cycle as acetyl-CoA.  There are several
    isoenzymes of ALDH with different kinetic and binding parameters that
    influence acetaldehyde oxidation rates.

         ALDH activity has been localized in the respiratory tract
    epithelium (excluding olfactory epithelium) in rats, in the renal
    cortex and tubules in the dog, rat, guinea-pig, and baboon, and, in
    the testes in the mouse.

         Acetaldehyde is metabolized by mouse and rat embryonic tissue
     in vitro. Acetaldehyde crosses the rat placenta, in spite of
    placental metabolism.

         Though there is some metabolism of acetaldehyde in human renal
    tubules, the liver is the most important metabolic site.

         Several isoenzymic forms of ALDH have been identified in the
    human liver and other tissues.  There is polymorphism for the
    mitochondrial ALDH.  Subjects who are homozygous or heterozygous for a
    point mutation in the mitochondrial ALDH corresponding gene have low
    activity of this enzyme, metabolize acetaldehyde slowly, and are
    intolerant of ethanol.

         The metabolism of acetaldehyde can be inhibited by
    crotonaldehyde, dimethylmaleate, phorone, disulfiram, and calcium


    a  ALDH = acetaldehyde dehydrogenase.

    b  NAD = nicotinamide adenine dinocleotide.

    1.5.3  Reaction with other components

         Acetaldehyde forms stable and unstable adducts with proteins. 
    This can impair protein function, as evidenced by inhibition of enzyme
    activity, impaired histone-DNA binding, and inhibition of
    polymerization of tubulin.

         Unstable adducts of acetaldehyde of undetermined significance
    occur  in vitro with nucleic acids.

         Acetaldehyde can react with various macromolecules in the body,
    preferentially those containing lysine residues, which can lead to
    marked alterations in the biological function of these molecules.

    1.6  Effects on organisms in the environment

    1.6.1  Aquatic organisms

         LC50s in fish ranged from 35 (guppy) to 140 mg/litre (species
    not specified).  An EC5 of 82 mg/litre and an EC50 of 42 mg/litre
    were reported for algae and Daphnia magna, respectively.

    1.6.2  Terrestrial organisms

         Acetaldehyde in air appears to be toxic for some microorganisms
    at relatively low concentrations.

         Aphids were killed when exposed to acetaldehyde at a
    concentration of 0.36 µg/m3 for 3 or 4 h.

         Median lethal values were 8.91 mg/litre per h and 7.69 mg/litre
    per h for the slug species, Arion hortensis and Agriolimax
    reticulatus, respectively.

         Inhibition of seed germination in the onion, carrot, and tomato
    by acetaldehyde (up to 1.52 mg/litre) was reversible, whereas
    inhibition of  Amaranthus palmeri, similarly exposed, was
    irreversible.  Acetaldehyde at 0.54 µg/m3 damaged lettuce.

    1.7  Effects on experimental animals and  in vitro test systems

    1.7.1  Single exposure

         LD50s in rats and mice and LC50s in rats and Syrian hamsters
    showed that the acute toxicity of acetaldehyde is low.  Acute dermal
    studies were not identified.

    1.7.2  Short- and long-term exposures

         In repeated dose studies, by both the oral and inhalation routes,
    toxic effects at relatively low concentrations were limited
    principally to the sites of initial contact.  In a 28-day study in
    which acetaldehyde at 675 mg/kg body weight (no-observedeffect level
    (NOEL): 125 mg/kg body weight) was administered in the drinking-water
    to rats, effects were limited to slight focal hyperkeratosis of the
    forestomach.  Following administration of a single dose level (0.05%
    in the drinking-water) for 6 months (estimated by the Task Group to be
    approximately 40 mg/kg body weight) in a biochemical study,
    acetaldehyde induced synthesis of rat liver collagen, an observation
    that was supported by  in vitro data.

         Following inhalation, NOELs for respiratory effects were
    275 mg/m3 in rats exposed for 4 weeks and 700 mg/m3 in hamsters
    exposed for 13 weeks.  At lowest-observed-effect levels, degenerative
    changes were observed in the olfactory epithelium in rats
    (437 mg/m3) and the trachea (2400 mg/m3) in hamsters. 
    Degenerative changes in the respiratory epithelium and larynx were
    observed at higher concentrations.  No repeated dose dermal studies
    were identified.

    1.7.3  Reproduction, embryotoxicity, and teratogenicity

         In several studies, parenteral exposure of pregnant rats and mice
    to acetaldehyde induced fetal malformations.  In the majority of these
    studies, maternal toxicity was not evaluated.  No data on reproductive
    toxicity were identified.

    1.7.4  Mutagenicity and related end-points

         Acetaldehyde is genotoxic  in vitro, inducing gene mutations,
    clastogenic effects, and sister-chromatid exchanges (SCEs) in
    mammalian cells in the absence of exogenous metabolic activation. 
    However, negative results were reported in adequate tests on
    Salmonella.  Following intraperitoneal injection, acetaldehyde induced
    SCEs in the bone marrow of Chinese hamsters and mice.  However,
    acetaldehyde administered intraperitoneally did not increase the
    frequency of micronuclei in early mouse spermatids.  There is indirect
    evidence from  in vitro and  in vivo studies to suggest that
    acetaldehyde can induce protein-DNA and DNA-DNA cross-links.

    1.7.5  Carcinogenicity

         Increased incidences of tumours have been observed in inhalation
    studies on rats and hamsters exposed to acetaldehyde.  In rats, there
    were dose-related increases in nasal adenocarcinomas and squamous cell
    carcinomas (significant at all doses).  However, in hamsters,
    increases in nasal and laryngeal carcinomas were non-significant.  All
    concentrations of acetaldehyde administered in the studies induced
    chronic tissue damage in the respiratory tract.

    1.7.6  Special studies

         Adequate studies on the potential neuro- and immunotoxicity of
    acetaldehyde were not identified.

    1.8  Effects on humans

         In limited studies on human volunteers, acetaldehyde was mildly
    irritating to the eyes and upper respiratory tract following exposure
    for very short periods to concentrations exceeding approximately 90
    and 240 mg/m3, respectively.  Cutaneous erythema was observed in
    patch testing with acetaldehyde, in twelve subjects of "Oriental

         One limited investigation in which the incidence of cancer was
    examined in workers exposed to acetaldehyde and other compounds has
    been reported.

         On the basis of indirect evidence, acetaldehyde has been
    implicated as the putatively toxic metabolite in the induction of
    alcohol-associated liver damage, facial flushing, and developmental

    1.9  Evaluation of human health risks and effects on the environment

         The acute toxicity of acetaldehyde by the inhalation or oral
    route in studies conducted on animals was low.  According to studies
    on humans and animals, acetaldehyde is mildly irritating to the eyes
    and the upper respiratory tract.  In limited studies on human
    volunteers, acetaldehyde was mildly irritating to the eyes and upper
    respiratory tract (section 1.8).  Cutaneous erythema has also been
    observed in the patch testing of humans. Although a possible mechanism
    has been identified, available data are inadequate to assess the
    potential of acetaldehyde to induce sensitization.

         Available data on the effects of acetaldehyde following ingestion
    are limited.  Following oral administration of 675 mg/kg body weight
    per day to rats, a borderline increase in hyper-keratosis of the
    forestomach was observed (NOEL: 125 mg/kg body weight).  In rats
    exposed to a dose level of approximately 40 mg acetaldehyde/kg body
    weight in the drinking-water for 6 months, there was an increase in
    collagen synthesis in the liver, the significance of which is unclear.

         On the basis of studies on rats and hamsters, the target tissue
    in inhalation studies is the upper respiratory tract.  In available
    studies, the lowest concentration at which effects were observed was
    437 mg/m3 following administration for 5 weeks.  The NOELs
    identified for respiratory effects were 275 mg/m3 in rats exposed
    for 4 weeks and 700 mg/m3 in hamsters exposed for 13 weeks.

         At concentrations that induced tissue damage in the respiratory
    tract, increased incidences were observed of nasal adenocarcinomas and
    squamous cell carcinomas in the rat and laryngeal and nasal carcinomas
    in the hamster.

         There is evidence to suggest that acetaldehyde causes genetic
    damage to somatic cells  in vivo.

         Available data are inadequate for the assessment of the potential
    reproductive, developmental, neurological, or immunological effects
    associated with exposure to acetaldehyde in the general, or
    occupationally exposed, populations.

         On the basis of data on irritancy in humans, a tolerable
    concentration of 2 mg/m3 has been derived.  Since the mechanism of
    induction of tumours by acetaldehyde has not been well studied, two
    approaches were adopted for the provision of guidance with respect to
    this end-point, i.e., the development of a tolerable concentration
    based on division of an effect level for irritancy in the respiratory
    tract of rodents by an uncertainty factor, and, estimation of lifetime
    cancer risk based on linear extrapolation.  The tolerable
    concentration is 0.3 mg/m3.  The concentrations associated with a
    10-5 excess lifetime risk are 11-65 µg/m3.

         The limited available data preclude definitive conclusions
    concerning the potential risks of acetaldehyde for environmental
    biota.  However, on the basis of the short half-lives of acetaldehyde
    in air and water and the fact that it is readily biodegradable, the
    impact of acetaldehyde on organisms in the aquatic and terrestrial
    environments is expected to be low, except, possibly, during
    industrial discharges or spills.


    2.1  Identity

    Chemical formula:       C2H4O

    Chemical structure:     CH3-CHO

    Common name:            acetaldehyde

    Common synonyms:        ethanal; acetic aldehyde; acetylaldehyde;
                            ethylaldehyde; diethylacetal;
                            1,1-diethyoxy ethane

    CAS chemical name:      acetaldehyde

    CAS registry number:    75-07-0

    RTECS registry number:  AB 1925000

    2.2  Physical and chemical properties

         The most important physical and chemical properties of
    acetaldehyde are given in Table 1.

         Acetaldehyde is a volatile liquid with a pungent, suffocating
    odour that is fruity in dilute concentrations. The odour threshold for
    acetaldehyde is reported to be 0.09 mg/m3 (0.05 ppm).  This was a
    geometric average of all available literature data (Amoore & Hautala,
    1983).  In the case of carbon dioxide solutions in acetaldehyde, the
    acetaldehyde odour is weakened by the carbon dioxide (Hagemeyer,

         Acetaldehyde is a highly reactive compound that undergoes
    numerous condensation, addition, and polymerization reactions.  It
    decomposes at temperatures above 400°C, forming principally methane
    and carbon monoxide.  Acetaldehyde is highly flammable when exposed to
    heat or flame, and, in air, it can be explosive.  Acetaldehyde can
    react violently with acid anhydrides, alcohols, ketones, phenols,
    NH3, HCN, H2S, P, halogens, isocyanates, strong alkalies, and
    amines.  It is miscible in all proportions with water and the most
    common organic solvents.  In aqueous solutions, acetaldehyde exists in
    equilibrium with the hydrate, CH3 CH(OH)2.  The enol form, vinyl
    alcohol (CH2=CHOH) exists in equilibrium with acetaldehyde to the
    extent of approximately one molecule per 30 000 (Hagemeyer, 1978).

    Table 1.  Physical and chemical properties of acetaldehydea

    Colour                                    colourless
    Relative molecular mass                   44.1
    Boiling point at 101.3 kPa                20.2°C
    Melting point                             -123.5°C
    Octanol/water partition coefficient as    0.63
    log Pow
    Flash point, closed cup                   -38°C
    Autoignition temperature                  185-193°C
    Explosion limits of mixtures with air     4.5-60.5 vol % acetaldehyde
    Vapour pressure at   -50°C                2.5 kPa
                           0°C                44.0 kPa
                       20.16°C                101.3 kPa
    Specific gravity (20/4)                   0.778
    Relative vapour density                   1.52
    Refractive index 20/D                     1.33113
    Dissociation constant at 0°C, Ka          0.7 × 10-14
    Solubility                                miscible in water and most
                                              common solvents

    a  From: Hagemeyer (1978); IPCS/CEC (1990).

         Commercial acetaldehyde should have the following typical
    specifications: purity, 99% min; acidity (as acetic acid), 0.1% max,
    and a specific gravity of 0.804-0.811 (0°/20°C) (US NRC, 1981).

    2.3  Conversion factors

    1 mg acetaldehyde/m3 air    =  0.56 ppm at 25°C and 101.3 kPa
                                   (760 mmHg).
    1 ppm                       =  1.8 mg acetaldehyde/m3 air.

    2.4  Analytical methods

         Several analytical procedures used for the sampling and
    determination of acetaldehyde in various media are summarized in
    Table 2.

        Table 2.  Sampling, preparation, and determination of acetaldehydea

    Medium     Sampling method                   Analytical method      Detection     Sample         Comments                   Reference
                                                                        limit         size

    Air      collection in a midget              HPLC with             18 µg/m3      20 litre      designed for analysis of    Lipari & Swarin
             impinger containing 2,4-DNPH        spectrophotometric                                automobile exhaust          (1982)
             in acetonitrile with                detection
             perchloric acid as catalyst

    Air      collection in a tube containing     HPLC with             0.9 µg/m3     2 litre       suitable for analysis of    Jarke et al.
             a thermal stable organic polymer    spectrophotometric                                indoor and outdoor air      (1981)
             based on 2,6-diphenyl-p-            detection
             phenylene oxide

    Air      adsorption on a silica gel          GC-FTD                0.09-0.45     50-100        suitable for analysis of    Aoyama & Yashiro
             treated with 2,4-DNPH                                     µg/m3         litre         smog and automobile         (1983)

    Air      collection in a 2,4-DNPH            HPLC with             < 18 µg/m3    < 20 litre    suitable for long-term      Tejada (1986)
             coated Sep-PAK cartridge,           spectrophotometric                                sampling at low µg/m3
             acidified with HCl                  detection                                         (ppb) levels in ambient
                                                                                                   air, or, for short-term
                                                                                                   sampling at low mg/m3
                                                                                                   (ppm) levels in diluted
                                                                                                   automotive exhaust

    Table 2 (contd).

    Medium     Sampling method                   Analytical method      Detection     Sample         Comments                   Reference
                                                                                      limit          size

    Air      collection in annular denuders      HPLC with UV          0.36 µg/m3    100 litre     suitable for analysis of    Possanzini et
             coated with 2,4-DNPH                absorbance or                                     outdoor and indoor          al. (1987)
             detection                           voltametric

    Air      collection and derivatization       HPLC with UV          90 µg/m3      5 litre       suitable for personal       Binding et al.
             on 2,4-DNPH coated                  detection                                         monitoring of 5-min,        (1986)
             Chromosorb P                                                                          short-term values as
                                                                                                   well as for continuous
                                                                                                   sampling over a whole
                                                                                                   work shift

    Air      collection on DNPH-coated C18       HPLC with UV          12 ng per                   suitable for ambient        Grosjean (1991)
             cartridge                           detection             cartridge                   monitoring

    Air      collection and derivatization       HPLC with UV          32 mg/m3b     60 litre      suitable for short-term     US NIOSH (1987)
             in midget bubblers containing       detection                                         exposure sampling;
             Girard T solution                                                                     interference with other
                                                                                                   aldehydes and volatile
                                                                                                   ketones should be

    Table 2 (contd).

    Medium     Sampling method                   Analytical method      Detection     Sample         Comments                   Reference
                                                                        limit         size

    Air      collection in a Chromosorb 104      GC-FID                0.1 µg/litre  1.5 litre     suitable for monitoring     Watanabe (1988)
             tube installed in an automated                                                        of outdoor and indoor
             sampler                                                                               pollution

    Air      collection on a XAD-2 sorbent       GC-FID                1.3 mg/m3c    3 litre       suitable for short-term     US NIOSH (1989)
             coated with 2-(hydroxymethyl)-                                                        exposure sampling and for
             piperidine                                                                            analysis of field samples

    Water    derivatization in a two-phase       HPLC with             21 µg         --            designed for analysis of    Facchini et
             system by addition of 2,4-DNPH      electrochemical                                   fog and rain water          al. (1986)
             and isooctane                       detection

    Water    purging with nitrogen gas and       sweeping by rapid     200 µg/       5 ml          suitable for analysis of    Spingarn et
             collection on a Tenax GC            heating of trap       litre                       aqueous solution and        al. (1982)
             sorbent and silica gel trap         into GC-MS                                        industrial effluent

    Water    derivatization with 2,4-DNPH        HPLC; the reaction    < 10 µg per   1 ml          suitable for routinely      Steinberg &
             (in acetonitrile)                   mixture is analysed   sample                      monitoring rain, fog,       Kaplan (1984)
             directly, without                   and mist samples
             prior separation of
             the DNPH-derivatives

    Table 2 (contd).

    Medium        Sampling method                  Analytical method      Detection     Sample         Comments                 Reference
                                                                          limit         size

    Water      collection in a PTFE-cartridge      HPLC with UV         0.3 µg/litre   500 ml       designed for analysis of   Takami et
               packed with sulfonated cation       detection                                        water samples at the low   al. (1985)
               exchange resin charged with                                                          µg/litre levels

    Water      collection of aqueous solution      HS-GC-FID            25 µg/litre    10 ml        designed for the           Gramiccioni
               in vials, no special treatments                                                      quantification of          et al. (1986)
               released from plastics                                                               acetaldehyde
               into aqueous foods

    Water      collection on cyanogen bromide      spectrophotometric   0.6 mg/        30 µlitre    immobilized aldehyde       Almuaibed &
               activated Sepharose 4B              detection            litre                       dehydrogenase makes the    Townshend (1987)
               containing aldehyde                                                                  determination more
               dehydrogenase; soluble aldehyde                                                      economic and simpler
               dehydrogenase injected in the
               sampler flow stream using a
               double injection technique

    Beverage   collection of the 2,6-              HPLC with            0.01 µg per    15 ml        designed for analysis of   Okamoto et
               dimethylpyridine derivative         spectrophotometric   sample                      wine                       al. (1981)
               on a 3-aminopropyl-                 detection
               triethoxysiloxane or a
               Nucleosil 5NH2 treated silica
               gel with propionaldehyde as
               internal standard

    Table 2 (contd).

    Medium        Sampling method                  Analytical method   Detection    Sample         Comments                     Reference
                                                                       limit        size

    Beverage   steam distillation followed by        HPLC with UV      ± 5 µg/      500 ml         designed for analysis of    Piendl et
               liquid liquid extraction,             detection         litre                       beer                        al. (1981)
               derivatization with p-nitrobenzyl-
               oxyamine-hydrochloride with T-2
               undecenal as internal standard

    Beverage   conversion of acetaldehyde            HS-GC-FID         ± 1 mg/      5 ml           designed as a rapid         Jones et al.
               acetals and bisulfite addition                          litre                       means by which the          (1986)
               products to free acetaldehyde by                                                    acetaldehyde production
               a series of 1-min acid, base,                                                       and consumption
               and iodine treatments followed                                                      pattern of different
               by a 10-min equilibration period                                                    wines can be predicted

    Breast     collection of volatile compounds      thermal           --           60 ml          designed for                Pellizari et
    milk       on a Tenax cartridge after            desorption                                    determination in breast     al. (1982)
               warming milk and purging with         into GC-MS                                    milk

    Blood      precipitation of protein with         GC headspace      4.4 µg per   -              designed for analysis of    Eriksson et
               perchloric acid                       analysis          sample                      blood in order to reduce    al. (1982)
               artificial formation
               of acetaldehyde

    Blood      derivatization with 2,4-DNPH          HPLC with UV      4.4 ng per   2 ml           designed for analysis of    Pezzoli et
               with butyraldehyde as internal        detection         sample                      blood                       al. (1984)
               standard and perchloric acid
               (for protein precipitation)

    Table 2 (contd).

    Medium    Sampling method                   Analytical method     Detection      Sample           Comments                  Reference
                                                                      limit          size

    Blood   rapid separation                    plasma: HPLC with     > 0.9 ng      0.5 ml          designed for analysis of   Di Padova et
            plasma: deproteinization and        spectrophotometric    per sample    plasma          plasma and red blood       al. (1986)
            derivatization with 2,4-DNPH        detection                                           cells
            haemolysate: deproteinization       haemolysate:
            and mixed with semicarbazide        HS-GC-FID

    Blood   separation of plasma and            HPLC with             11 µg per     1 ml            suitable for clinical      Peterson &
            haemolysate plasma:                 fluorescence          sample        plasma          use                        Polizzi (1987)
            1,3-cyclo-hexanedione and           detection                           or RBC
            isooctane haemolysate:                                                  haemolysate
            1,3-cyclo-hexadione both in
            presence of ammonium ion

    Blood   reaction with 1,3-cyclo-hexanone    HPLC with             4.4 µg per    50-100          designed for microassays   Ung-Chhun &
            in the presence of ammonium ion     fluorescence          sample        µlitre          with negligible            Collins (1987)
            propionaldehyde used as internal    detection                                           interference

    Blood   collection in an organic solution   HPLC with             > 0.13 µg     1 ml            designed for analysis of   Rideout et
            of 2-diphenylacetyl-                spectrofluometric     per sample                    blood; with minor          al. (1986)
            1,3-indandione-1-hydrazone, and     detection                                           modifications also
            forming fluorescent azine                                                               suitablefor analysis of
            derivative-precipitation of                                                             beverages, breath, and
            proteins                                                                                tissue

    Table 2 (contd).

    Medium     Sampling method                   Analytical method      Detection     Sample         Comments                   Reference
                                                                        limit         size

    Blood    reaction with methanolic solution   HPLC; the             4.4 µg/litre  1 ml blood    suitable for assessment     Lynch et
    and      of 2,4-DNPH, with                   acetaldehyde adduct                 1 g tissue    of acetaldehyde levels in   al. (1983)
    tissue   dinitrophenyl-[14C]-formaldehyde    was identified by                                 clinical and experimental
             as internal standard                co-chromatography                                 studies of ethanol
                                                 with the authentic                                metabolism and alcoholic
                                                 derivative and by                                 beverages
                                                 mass spectrometry

    a  2,4-DNPH = 2,4-dinitrophenylhydrazine; HPLC = high pressure liquid chromatography; GC-FID = gas chromatography with flame ionization
       detection; GC-FTD = gas chromatography with flame thermionic detection; GC-MS = gas chromatography with mass spectrometric detection;
       HS-GC-FID = head space gas chromatography with flame ionization detection.
    b  minimum working range (estimated LOD: 1.6 mg/m3).
    c  minimum working range (estimated LOD: 0.67 mg/m3).

         The most specific and sensitive analytical method, widely used to
    date, is based on the reaction of acetaldehyde with
    2,4-dinitro-phenylhydrazine (2,4-DNPH) and the subsequent analysis of
    the hydrazone derivatives by high pressure liquid chromatography
    (HPLC) or gas chromatography (GC).  Methods mentioned by US NIOSH are
    based on derivatization with Girard T solution followed by HPLC
    analysis with UV detection (US NIOSH, 1987), or, on derivatization
    with 2-(hydroxymethyl)piperidine followed by GC analysis with a flame
    ionization detector (FID) (US NIOSH, 1989).  In the method based on
    Girard T derivation, other volatile aldehydes compete for the Girard T
    reagent.  Chromatographic conditions may be adjusted to resolve
    acetaldehyde from other aldehydes.

         Spingarn et al. (1982) determined volatile organic compounds in
    aqueous solutions, including acetaldehyde, using a technique in which
    the compounds were purged from the solution by bubbling with an inert
    gas into a trap containing a Tenax sorbent and silica gel.  The
    analytes were separated by GC and detected with either specific
    ionization detection or MS.  An improvement in detection limits,
    compared with those of the widely used spectrophotometric method of
    analysing carbonyls in aqueous solution, was obtained by Facchini et
    al. (1986) by means of an electrochemical detector.

         In the determination of acetaldehyde in blood, two main
    difficulties exist.  The first is related to its disappearance from
    blood prior to measurement and the second is related to the formation
    of acetaldehyde in blood after collection.  According to Pezzoli et
    al. (1984), the addition of butyraldehyde to blood, as an internal
    standard, immediately after withdrawal, obviates some of the
    inconveniences in the determination of acetaldehyde in blood.  The
    addition of butyric acid makes it possible to obtain results both for
    the interaction of the aldehyde group of the acetaldehyde with amino
    groups, and for the formation and extraction of the derivative
    compound.  However, Di Padova et al. (1986) stated that the addition
    of butyraldehyde was not specific for the determination of the
    acetaldehyde but was related to the aldehyde group reactivity. 
    Therefore, they described an improved procedure for measuring
    acetaldehyde in plasma, based on rapid separation, 2,4-DNPH
    derivatization, and HPLC analysis, and a procedure for measuring
    acetaldehyde in red blood cells, based on the use of a semicarbazide
    solution and analysis by head space gas chromatography.


    3.1  Natural occurrence

         Acetaldehyde is a metabolic intermediate in humans and higher
    plants and it is a product of alcohol fermentation (IARC, 1985).  It
    has been identified as a volatile component of mature cotton leaves
    and cotton blossoms (Berni & Stanley, 1982) and as a component in the
    essential oil of alfalfa at a concentration of about 0.2% (Kami,
    1983).  It occurs in food, various fruits, and several spices (see
    section 5.1.4) and in oak and tobacco leaves (Furia & Bellanca, 1975;
    US NRC, 1985).

         Acetaldehyde is formed in the atmosphere in a variety of ways. 
    It is generated by the oxidation of non-methane hydrocarbons both in
    the background troposphere and in photochemical smog (Grosjean, 1982).

    3.2  Anthropogenic sources

    3.2.1  Production  Production levels and processes

         Until 1968, most acetaldehyde produced in the USA was made by the
    partial oxidation of ethanol over a silver catalyst; however,
    currently less than 5% of US production is based on this process.  The
    liquid-phase oxidation of ethylene using a catalytic solution of
    palladium and copper chlorides was first used commercially in the USA
    in 1960 and more than 80% of the world production of acetaldehyde is
    made by this process.  The remainder is produced by the oxidation of
    ethanol and the hydration of acetylene.  Acetaldehyde is produced by a
    limited number of companies over the world.  The total production of
    acetaldehyde in the USA in 1982 amounted to 281 thousand tonnes. 
    Total acetaldehyde production in Western Europe in 1982 was 706
    thousand tonnes, and the production capacity was estimated to have
    been nearly 1 million tonnes.  In Japan, the estimated production in
    1981 was 323 thousand tonnes (Hagemeyer, 1978; IARC, 1985).  Emissions

         Eimutis et al. (1978) estimated that the annual atmospheric
    emissions of acetaldehyde in the USA amounted to 12.2 thousand tonnes
    (Table 3).  Emissions of acetaldehyde in the Netherlands in the year
    1980 were reported to be 584 tonnes (Guicherit & Schulting, 1985).

    Table 3.  Emission and sources of acetaldehyde in the USA

    Source                                                Emissions

    Residential external combustion of wood                 5056.4
    Coffee roasting                                         4411.4
    Acetic acid manufacture                                 1460.9
    Vinyl acetate manufacture from ethylene                 1094.6
    Ethanol manufacture                                       57.8
    Acrylonitrile manufacture                                 51.6
    Acetic acid manufacture from butane                       20.8
    Crotonaldehyde manufacture                                 4.5
    Acetone and phenol manufacture from cumene                 1.9
    Acetaldehyde manufacture by hydration of ethylene          0.5
    Polyvinyl chloride manufacture                             0.2
    Acetaldehyde manufacture by oxidation of ethanol           0.1

    3.2.2  Uses

         Acetaldehyde is an important intermediate in the production of
    acetic acid, ethyl acetate, peracetic acid, pentaerythritol, chloral,
    glyoxal, alkylamines, and pyridines (Hagemeyer, 1978).  The use
    pattern for the estimated 281 thousand tonnes of acetaldehyde produced
    in the USA in 1982 was as follows: acetic acid 61%, pyridine and
    pyrine bases 9%, peracetic acid 8%, pentaerythritol 7%, 1,3-butylene
    glycol 2%, chloral 1%, and other applications (including use as a food
    additive and exports) 12%.  The use pattern for the estimated 706
    thousand tonnes of acetaldehyde produced in Western Europe was as
    follows: acetic acid 62%, ethyl acetate 19%, pentaerythritol 5%,
    synthetic pyridines 3%, and all other uses 11% (IARC, 1985).

         Acetaldehyde is used for the flavourings: berry, butter,
    chocolate, apple, apricot, banana, grape, peach, black walnut, and
    rum, and it is used in the following foods: beverages, ice cream and
    ices, candy, baked goods, gelatin desserts, and chewing gum (Furia &
    Bellanca, 1975; US NRC, 1981, 1985).  Acetaldehyde is also used in
    perfumes, aniline dyes, plastics, in the manufacture of synthetic
    rubber, in the silvering of mirrors, in the hardening of gelatin
    fibres, and in the laboratory (Verschueren, 1983).

    3.2.3  Waste disposal

         Degradation of hydrocarbons, sewage, and solid biological wastes
    produces acetaldehyde.  It has been detected in effluents from
    sewage-treatment plants and chemical plants (US EPA, 1975; Shackelford
    & Keith, 1976).

         Acetaldehyde has been identified as a constituent in the wastes
    from petroleum refining, coal processing, the oxidation of alcohols,
    saturated hydrocarbons, or ethylene, and the hydration of acetylene
    (IARC, 1985).

    3.2.4  Other sources

         Acetaldehyde is detected as a combustion product of plastics and
    polycarbonate and polyurethane foams of western European origin
    (Hagen, 1967; Boettner et al., 1973).

         Acetaldehyde occurs in vehicle exhaust at levels of
    1.4-8.8 mg/m3 in gasoline exhaust, about 5.8 mg/m3 in diesel
    exhaust (Verschueren, 1983), and 51.6% acetaldehyde/ n-hexane GC peak
    area ratio in exhaust gas oxygenates (Hugues & Hum, 1960).  It also
    occurs in the open burning and incineration of gas, fuel oil, and
    coal, and evaporation products of perfumes (Verschueren, 1983).

         Acetaldehyde has been identified in fresh tobacco leaves and in
    tobacco smoke (concentrations ranging from 2.1 to 4.6 mg/litre smoke)
    (Buyske et al., 1956; Osborne et al., 1956; Mold & McRae, 1957).

         When Lipari et al. (1984) measured aldehyde emissions from
    wood-burning fireplaces, they ranged from 0.08 to 0.20 g/kg of wood
    burned, based on tests with cedar, jack pine, red oak, and green ash.

         Acetaldehyde emissions from wood-burning furnaces and
    stoves were also measured in a Swedish study (Rudling et al., 1981)
    and in a Norwegian study (Ramdahl et al., 1982).  In the Swedish
    study, the emissions ranged from 1-72 mg/kg wood in prechamber ovens
    to 9-710 mg/kg wood in fireplace stoves. In the Norwegian study, the
    reported emissions from stoves were 14.4 mg/kg dry wood under normal
    burning conditions and up to 992 mg/kg dry wood under low-efficiency


    4.1  Transport and distribution between media

         Acetaldehyde can enter the atmosphere during production of the
    compound itself, as a product of incomplete combustion, and also as a
    by-product of fermentation (Grosjean, 1982).

         Photochemical oxidation of acetaldehyde has been shown to be an
    important process in the chemistry of photochemical smog (Bagnall &
    Sidebottom, 1984; Leone & Seinfeld, 1984).  Present theories ascribe
    the importance of acetaldehyde to its being a precursor of
    peroxyacetylnitrate (PAN) in polluted atmospheres (Kopczynski et al.,
    1974; Grosjean et al., 1983; Bagnall & Sidebottom, 1984; Moortgat &
    McQuigg, 1984).  Acetaldehyde is likely to be a precursor of acetic
    acid, which is a component of natural precipitation and contributes to
    its acidity (Moortgat & McQuigg, 1984).

         Intercompartmental transport of acetaldehyde is expected to be
    limited, because of its high reactivity.  However, because of the high
    vapour pressure of acetaldehyde, some transfer to air from water and
    soil can be expected.

         The tendency of acetaldehyde to adsorb on 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.  On the basis of the available
    empirical relationships derived for estimating Koc, a low soil
    adsorption potential is expected (Lyman et al., 1982).  Koch & Nagel
    (1988) calculated a soil sorption coefficient of 0.90 for
    acetaldehyde, and, therefore, acetaldehyde was classified as a
    compound with a very low sorption tendency.

    4.2  Abiotic degradation

         It is suggested that photo-induced atmospheric removal of
    acetaldehyde occurs predominantly via radical formation.  Singh et al.
    (1982) reported that photolysis and reaction with hydroxyl radicals
    cause a daily loss rate of about 80% of atmospheric acetaldehyde
    emissions.  Grosjean et al. (1983) reported that the reaction with
    hydroxyl radicals could remove 50-300 tonnes of carbonyls from the Los
    Angeles air over a 12-h daytime period and, thus, is considered to be
    a major removal process for all aldehydes.  The absolute rate constant
    for the reaction of the hydroxyl radical with acetaldehyde was
    determined over a temperature range of 26-153°C by Atkinson & Pitts
    (1978).  At 26°C, they obtained a rate constant of (1.60 ± 0.16) ×
    10-11 cm3 per molecule per second.  This results in a half-life
    for acetaldehyde of 10 h, using a 12-h daytime average hydroxyl

    radical concentration of 2 × 10-15 mol/litre (Lyman et al., 1982). 
    Hustert & Parlar (1981) reported that 49.5% acetaldehyde was
    photochemically degraded (reaction with hydroxyl radicals) after a 2-h
    radiation (lambda > 230 nm) at 25°C, which, contrary to Atkinson &
    Pitts (1978), shows a half-life of 2 h.  Atkinson et al. (1984)
    obtained a rate constant of (1.34 ± 0.28) × 10-15 for the gas-phase
    reaction of nitrate radicals with acetaldehyde at 25°C.  This results
    in a half-life for acetaldehyde of 59.6 h using a 12-h nighttime
    average nitrate radical concentration of 4.0 × 10-12 mol/litre
    (Atkinson et al., 1987).

         There is a considerable amount of evidence that acetaldehyde in
    aqueous solution is in equilibrium with its hydrated form
    CH3CH(OH)2.  The degree of hydration decreases with increasing
    temperature (e.g., at 0°C, the fraction of acetaldehyde hydrated is
    0.73; at 25°C, it is 0.59) (Bell & Clunie, 1952).

         Von Burg & Stout (1991) reported a half-life of 1.9 h for
    acetaldehyde in river water; no other details were provided.

    4.3  Biodegradation

         Several studies have revealed significant degradation of
    acetaldehyde by mixed cultures obtained from sludges and settled
    sewage.  Hatfield (1957) reported the ability of acclimatized sludge
    to oxidize acetaldehyde (major portion of the biological and chemical
    oxygen demand (BOD and COD) removed within a 4-h aeration period). 
    Ludzack & Ettinger (1960) determined the BOD for acetaldehyde in
    activated sludge at 20°C and found that 93% of the acetaldehyde was
    removed after an observation period of 1/3-5 days and an
    acclimatization period of 30 days.  Thom & Agg (1975) and Speece
    (1983) also reported that acetaldehyde was easily biodegradable by
    biological sewage treatment (additional information was not provided). 
    However, Gerhold & Malaney (1966) reported little degradation of
    acetaldehyde by unacclimatized municipal sludge with a BOD of 27.6% as
    a percentage of the theoretical oxygen demand in 24 h.

         Acetaldehyde is also degraded by anaerobic biological treatment
    with unacclimatized acetate-enriched cultures.  A COD-removal of 97%
    was obtained at the end of a 90-day acclimatization period in
    completely mixed reactors with a 20-day hydraulic retention time, no
    solids recycle, and a final daily feed concentration of
    10 000 mg/litre (Chou & Speece, 1978).

         Acetaldehyde is reported to be readily biodegradable using the
    biodegradability MITI test, defined in OECD Guidelines for testing of
    chemicals (OECD, 1992).


    5.1  Environmental levels

    5.1.1  Air

         The concentrations of acetaldehyde in uncontaminated Arctic air
    masses, determined over a 24-h period, ranged from not detected to
    0.54 µg/m3 (Cavanagh et al., 1969).

         In samples collected during April 1981, the levels of
    acetaldehyde in the air in Pittsburg (PA) and Chicago (Il) were
    0.36-4.68 µg/m3 and 1.62-6.12 µg/m3, respectively (Singh et al.,
    1982).  In samples collected at 7 other locations in the USA between
    1975 and 1978, mean concentrations in ambient air were 5-124 µg/m3
    (Brodzinsky & Singh, 1982).

         Schulam et al.(1985) determined the levels of acetaldehyde in air
    (June-August 1983) in the urban location of Schenectady (NY) and the
    rural location of Whiteface Mountain (NY).  Concentrations of
    acetaldehyde were similar in the two locations (the levels of
    acetaldehyde varied from 0.36 to 1.44 µg/m3, detection limit:
    0.29 µg/m3).

         The average ambient atmospheric level of acetaldehyde, measured
    during the four seasons at Brookhaven National Laboratory (Upton, Long
    Island, NY) from July 1982 to May 1983, was 5.2 µg/m3, with a mean
    minimum concentration in winter of 1.8 µg/m3 and a mean maximum
    value in summer of 15.1 µg/m3 (Tanner & Meng, 1984).  Concentrations
    of acetaldehyde in the air in Tulsa, OK (sampled in July 1978), Rio
    Blanco County, CO (sampled in July 1978), and the Great Smoky
    Mountains, TN (sampled in September 1978), ranged up to 14.9, 16.9,
    and 23.9 µg/m3, respectively (Arntz & Meeks, 1981).

         Mean concentrations of acetaldehyde in the air in Tokyo during
    four seasons in 1985-86 ranged from 2.2 to 7.3 µg/m3 (Watanabe,
    1987).  Seasonal trends were not noted.  Concentrations of
    acetaldehyde in an environmental survey conducted by the Japan
    Environment Agency in 1987 ranged from 0.9 to 22 µg/m3 (number of
    sites sampled unspecified) (Japan Environment Agency, 1989).

         The mean concentration of acetaldehyde was 2 µg/m3 at three
    locations in the Netherlands, namely, the island of Terschelling (one
    of the least polluted areas of the country), Delft (suburban), and
    Vlaardingen (heavily industrialized area) (Guicherit & Schulting,

         Grosjean (1991) reported levels of acetaldehyde in ambient air,
    sampled every sixth day over a one-year period, at six locations in
    Southern California between September 1988 and September 1989. 
    Concentrations ranged up to 23.3 µg/m3 (13 ppb) with average values
    at the various locations ranging from 5.2 to 8.6 µg/m3
    (2.9-4.8 ppb).

         The mean concentration of acetaldehyde in fog samples taken in
    November, 1985 in the Po Valley (Italy) was 21 µg/litre (Facchini et
    al., 1986).  At urban locations in California (Los Angeles) and Alaska
    (Fairbanks), concentrations of acetaldehyde ranged from 0.007 to
    0.13 µg/ml in ice fog (Alaska), 0 to 0.11 µg/ml in rain (CA), 0 to
    0.59 µg/ml in cloud (CA), 0.10 to 0.11 µg/ml in mist (CA), and 0.006
    to 0.17 µg/ml in fog (CA) (Grosjean & Wright, 1983).

    5.1.2  Water

         No quantitative data on concentrations of acetaldehyde in raw
    water supplies were identified.

         Acetaldehyde has been detected in drinking-water from
    Philadelphia and Seattle at levels of up to 0.1 µg/litre (Keith et
    al., 1976).  No other information was provided.

    5.1.3  Soil

         Data on concentrations of acetaldehyde in soil were not

    5.1.4  Food

         Acetaldehyde has been detected in a wide range of foodstuffs (US
    NRC, 1981, 1985; Horvath et al., 1983; Feron et al., 1991), though few
    quantitative data are available.  In a variety of foodstuffs analysed
    in the Netherlands including fruits and juices, vegetables, milk
    products, bread, eggs, fish, meat, and alcoholic beverages,
    concentrations were generally less than 1 mg/kg, but occasionally
    ranged up to several hundred mg/kg, particularly in some fruit juices
    and alcoholic beverages; in vinegar, a maximum value of 1060 mg/kg was
    reported (Maarse & Visscher, 1992).   Acetaldehyde has been identified
    in alcoholic beverages, such as beer and wine (Okamoto et al., 1981;
    Piendl et al., 1981; Jones et al., 1986); levels in 18 English beers
    ranged from 2.6 to 13.5 mg/litre (Delcour et al., 1982).  Levels of
    0.2 to 1.2 mg/litre were found in wine samples in Japan (Okamato et
    al., 1981), while Margeri et al. (1984) reported levels of
    acetaldehyde in wines ranging between about 30 and 80 µg/litre.

         Acetaldehyde has been detected, but not quantified, in breast
    milk in the USA (detection limit not reported) (Pellizari et al.,

    5.1.5  Cigarette smoke

         Acetaldehyde is present in tobacco leaves and in cigarette smoke
    (Furia & Bellanca, 1975; US NRC, 1985).  Hoffman et al. (1975)
    detected acetaldehyde in the smoke of tobacco (980 µg per cigarette)
    and marijuana (1200 µg/cigarette).  The concentration in smoke from
    several cigarettes ranged from 0.87 to 1.22 mg per cigarette or from
    1.14 to 1.37 mg/cigarette, depending on the method of detection.  The
    concentration of acetaldehyde in three types of low-tar cigarettes
    ranged from 0.09 to 0.27 mg/cigarette (Manning et al., 1983).

    5.2  General population exposure

         Acetaldehyde is a metabolic product of ethanol.  On the basis of
    the assumptions that a standard drink contains 10 g of ethanol and
    that about 90% of imbibed alcohol is metabolized to acetaldehyde,
    alcoholic beverages are  generally by far the most significant source
    of exposure to acetaldehyde for the general population.

         On the basis of the content of acetaldehyde in cigarettes
    reported in section 5.1.5, it is likely that cigarettes contribute
    significantly to the total intake of acetaldehyde by smokers. 
    Assuming that smoke contains about 1 mg acetaldehyde per cigarette,
    that 20 cigarettes are smoked per day, and a mean adult body weight of
    64 kg (WHO, in press), intake from mainstream smoke would be about
    300 µg/kg body weight per day.

         On the basis of the average dietary intake of food groups in
    different regions of the world (WHO, in press) and the contents of
    acetaldehyde in foodstuffs and non-alcoholic beverages in the
    Netherlands (Maarse & Visscher, 1992), food (particularly fruit
    juices) may be one of the principal sources of exposure to
    acetaldehyde in the general environment.  More representative data on
    mean concentrations in foodstuffs have not been identified, but, on
    the basis of the ranges of concentrations determined in the Dutch
    survey, intake in food is estimated to range from just less than 10 to
    several hundred µg/kg body weight per day.

         Data from recent studies in various locations in the world
    indicate that mean concentrations of acetaldehyde in ambient air range
    from 2 to 8.6 µg/m3 (Guicheret & Schulting, 1985; Watanabe, 1987;
    Grosjean, 1991) (section 5.1.1).  Data on concentrations of
    acetaldehyde in indoor air were not identified.  On the basis of a
    daily inhalation volume for adults of 22 m3, a mean body weight for
    males and females of 64 kg (WHO, in press), and the assumption that
    mean concentrations are approximately 5 µg/m3, the mean intake of
    acetaldehyde from ambient air for the general population is estimated
    to be 1.7 µg/kg body weight per day.

         Limited identified data on concentrations of acetaldehyde in
    drinking-water indicate that they are generally less than 0.1 µg/litre
    (Keith et al., 1976).  Assuming a daily volume of ingestion for adults
    of 1.4 litres and a mean body weight for males and females of 64 kg
    (WHO, in press), and that levels are less than 0.1 µg/litre, the
    estimated intake of acetaldehyde from drinking-water for the general
    population would not exceed 0.002 µg/kg body weight per day.

    5.3  Occupational exposure

         Workers are exposed to acetaldehyde in the organic chemicals
    industry and in the fabricated rubber, plastic, and fermentation
    industries (US NIOSH, 1980, 1981).  Concentrations of acetaldehyde
    were below the detection limits (1-3.4 mg/m3) in five studies in
    which the workroom air of plants, such as those in textile finishing,
    propylene bottle production, and ureaformaldehyde foam-insulation
    manufacturing, was monitored (Rosensteel & Tanaka, 1976; Ahrenholz &
    Gorman, 1980; Herrick, 1980; Chrostek & Shoemaker, 1981; Chrostek,
    1981).  Bittersohl (1975) reported levels of acetaldehyde of
    1-7 mg/m3 in the hydrogenation unit of a chemical factory after
    equipment leakages.

         Concentrations of acetaldehyde to which workers may be exposed
    near aircraft with low-smoke combustor engines were found to range
    from 139 to 394 µg/m3 (Miyamoto, 1986).


    6.1  Absorption

         No studies are available on animals or humans concerning the
    absorption of acetaldehyde.  However, the results of toxicity studies
    indicate that absorption via the lungs and gastrointestinal tract does
    occur.  The physical and chemical properties of acetaldehyde indicate
    that absorption via the skin is also possible.

    6.2  Distribution

    6.2.1  Animal studies  Distribution after inhalation exposure

         Distribution studies were conducted on overnight-starved, male
    Sprague-Dawley rats exposed (whole-body) to unknown concentrations of
    acetaldehyde vapour for 1 h.  Acetaldehyde was recovered in total
    blood, liver, kidneys, spleen, heart muscle, and skeletal muscle.  No
    other tissues were studied.  The concentration of acetaldehyde in the
    liver was relatively low (Hobara et al., 1985; Watanabe et al., 1986). 
    This can be attributed to rapid metabolism by hepatocytes.  Distribution to the embryo and fetus

         No studies are available concerning routes of relevance to

         Acetaldehyde was detected in the embryo up to 2 h after maternal
    ip injection of 200 mg acetaldehyde/kg body weight in CD-1 mice on day
    10 of gestation; acetaldehyde was measured within 5 min of injection. 
    Following maternal ip injection of 79 mg ethanol/kg body weight,
    acetaldehyde was measured up to 12 h after injection; however, levels
    were low and approached the limit of sensitivity (Blakley & Scott,

         Several other studies have demonstrated the presence of
    acetaldehyde in the embryos of rats (Espinet & Argiles, 1984; Gordon
    et al., 1985; Guerri & Sanchis, 1985; Clarke et al., 1986),
    guinea-pigs, and ewes (Clarke, 1988) exposed to ethanol. Embryological
    and cytogenic studies with ethanol and acetaldehyde in preimplantation
    mouse embryos  in vitro showed that acetaldehyde is three times more
    toxic than ethanol.  It has been suggested that the preimplantation
    mouse embryo is able to convert ethanol to acetaldehyde, and that the
    enzyme involved is alcohol dehydrogenase (ADH) (Lau et al., 1991)  Distribution to the brain

         In the only study involving a route of relevance to humans,
    following a single intragastric administration of 4500 mg ethanol/kg
    body weight to male and female Wistar rats, acetaldehyde was detected
    in the blood and in brain interstitial fluid collected from the
    caudate nucleus and the thalamushypothalamus region.  Following
    administration of disulfiram (an inhibitor of the aldehyde
    dehydrogenase (ALDH)-catalysed oxidation of acetaldehyde to acetate)
    20 h prior to exposure to ethanol, there was a 6-fold increase in the
    concentration of acetaldehyde in the blood and brain.  Although
    acetaldehyde was found in interstitial fluid, none was detected in
    whole brain (Westcott et al., 1980).

         In albino rats treated first with pyrazole, an inhibitor of ADH,
    injected (ip) with a solution of acetaldehyde in saline (200 mg/kg
    body weight per day) for 10 days, and then sacrificed 30 min after
    receiving the last injection, acetaldehyde was detected in the brain,
    liver, and blood (Prasanna & Ramakrishnan, 1984b, 1987).

         A study by Pettersson & Kiessling (1977) indicated the importance
    of ALDH activity, with a low Michaelis constant, in maintaining a low
    level of brain acetaldehyde during ethanol metabolism.  They detected
    acetaldehyde and ethanol in the cerebrospinal fluid of rats after
    intraperitoneal administration of ethanol alone or of ethanol followed
    by acetaldehyde.

    6.2.2  Human studies

         The percentage of acetaldehyde retained by 8 volunteers inhaling
    acetaldehyde vapour (100-800 mg/m3) from a recording respirometer
    ranged from 45 to 70%, at different respiratory rates.  Total
    respiratory tract retention was the same whether the vapour was
    inhaled through the nose or the mouth.  A direct relationship was
    found between the contact time and uptake, independent of rate.  Thus,
    the critical factor in determining acetaldehyde uptake is the duration
    of the ventilatory cycle (Egle, 1970).

         Baraona et al. (1987) used the blood of 5 healthy individuals, 6
    alcoholic patients, and 2 baboons to show that, after alcohol
    consumption, most of the blood acetaldehyde was found in the red blood
    cells.   In vivo, the acetaldehyde concentration in red cells was
    about 10 times higher than that in the plasma.  No significant
    variations were seen between the 3 groups.

         Studies using the perfused human placental cotyledon indicated
    that the human placenta has the potential to produce acetaldehyde,
    which can enter the fetal circulation.  Furthermore, partial transfer
    of acetaldehyde from maternal to fetal blood may occur (Karl et al.,

    6.3  Metabolism

    6.3.1  Animal studies

         The main pathway for the metabolism of acetaldehyde is shown in
    Fig. 1.

     FIGURE 1  Liver

         The main pathway for the metabolism of acetaldehyde is by rapid
    oxidation to acetate, which enters the citric acid cycle in an
    activated form as acetyl-CoA and is metabolized to CO2 and H2O.

         Although catalase and other oxidases may contribute to metabolism
    (Brien & Loomis, 1983), because of its high affinity, at least 90% of
    acetaldehyde is oxidized by mitochondrial ALDH (Hellström-Lindahl &
    Weiner, 1985) reducing NAD+ to NADH in the process.  This step can
    be blocked by disulfiram.

         There are multiple molecular forms of ALDH with different kinetic
    properties that influence the rate of removal of acetaldehyde
    (Marjanen, 1973; Parilla et al., 1974; Teschke et al., 1977).

         Acetaldehyde is a highly reactive molecule that can react with
    many other large or small molecules by adduction, condensation, or
    polymerization.  These pathways may have little quantitative
    significance in acetaldehyde metabolism, but the by-products may have
    biological significance (Collins et al., 1979; Sorrell & Tuma, 1985).

         Acetaldehyde is the primary metabolic product of ethanol
    oxidation.  Since ethanol is oxidized to acetaldehyde mole for mole,
    and, since the exposure to exogenous acetaldehyde is small, endogenous
    acetaldehyde resulting from the metabolism of ingested ethanol is
    likely to be the most important source of exposure for most people. 
    Oxidation of ethanol to acetaldehyde occurs predominantly under the
    influence of ADH, of which there are many isoenzymic forms.  Like
    ALDH, ADH is also NAD dependent.  The inseparable metabolism of
    ethanol and acetaldehyde results in the reduction of NAD+, thus,
    affecting the redox state of the liver causing secondary metabolic
    consequences.  Respiratory tract

         ALDH localization in the respiratory tract of Fischer-344 rats
    was studied by Bogdanffy et al. (1986).  Histochemical studies
    indicated activity principally in the nasal respiratory epithelium,
    especially in the supranuclear cytoplasm of ciliated epithelial cells. 
    Activity was also high in the Clara cells of the lower bronchioles. 
    The tracheal epithelia possessed only low levels of ALDH.  The
    olfactory epithelium was almost devoid of ALDH activity.

         Casanova-Schmitz et al. (1984) characterized at least 2
    isoenzymes of ALDH in rat nasal mucosa homogenates.  Kidneys

         In an  in vitro study, Michoudet & Baverel (1987a,b) studied the
    metabolism of acetaldehyde in isolated dog, rat, guinea-pig, and
    baboon kidney-cortex tubules.

         Acetaldehyde was found to be metabolized by the tubules at high
    rates and in a dose-dependent manner in all four species.  It was
    noted that, at all acetaldehyde concentrations, most of the
    acetaldehyde removed was recovered as acetate in dog, guinea-pig, and
    baboon, but not in rat kidney tubules.  Testes and ovaries

         There are no studies on the capacity of the testes or ovaries to
    mediate the biotransformation of acetaldehyde.  However, ALDH activity
    has been identified in the testes of Swiss-Webster mice (Anderson et
    al., 1985).  Embryonic tissue

         In an  in vitro study, the ability of CBA/beige mouse (10 days
    old) and Wistar rat (12 days old) embryos to metabolize acetaldehyde
    was reported by Priscott & Ford (1985).  Metabolism during pregnancy

         After intravenous administration of acetaldehyde (10 mg/kg body
    weight) blood acetaldehyde levels were higher in pregnant rats than in
    virgin rats.  Acetaldehyde at high concentrations was able to cross
    the placental barrier very rapidly.  At low maternal concentrations,
    it was metabolized by aldehyde dehydrogenase activity in the placenta
    and fetal liver, and acetaldehyde was not detected in fetal blood. 
    Above the acetaldehyde threshold, the metabolic capacity of the
    feto-placental unit was surpassed and acetaldehyde was detected in
    fetal blood (Zorzano & Herrera, 1989).

    6.3.2  Human studies

         No high quality studies of the  in vivo metabolism of
    acetaldehyde in humans have been identified.  Accurate assays for
    acetaldehyde in blood and tissues have only recently become available
    (Harade et al., 1978a,b).

         Human liver ALDH consists of at least 4 main isoenzymes, which
    are also present in many other tissues (Koivula, 1975; Goedde et al.,
    1979).  Mitochondrial ALDH is inactive in at least 40% of the Oriental
    population.  The frequently observed intolerance to alcohol (the
    "flushing" reaction) is linked to this deficiency, which is produced
    by an inherited positive mutation in the corresponding gene (Yoshida
    et al., 1984; Goedde & Agarwal, 1986, 1987; Hsu et al., 1988). 
    Subjects with phenotypic deficiency have always shown the presence of
    at least one mutant gene (heterozygous or homozygous) (Crabb et al.,
    1989; Goedde et al., 1989; Singh et al., 1989).

          In vitro, acetaldehyde (0.04-0.88 g/litre) was metabolized at
    high rates and in a dose-dependent manner in isolated human
    kidney-cortex tubules (Michoudet & Baverel, 1987b).

    6.4  Elimination

         In dogs, urinary excretion of acetaldehyde was essentially
    non-existent following administration of a single dose of 600 mg
    acetaldehyde/kg body weight, via a stomach tube (Booze & Oehme, 1986).

    6.5  Reaction with cellular macromolecules

    6.5.1  Proteins

         Acetaldehyde can react with nucleophilic groups, such as amino,
    hydroxyl, and sulfydryl groups, through nucleophilic attack on the
    carbonyl carbon atom of acetaldehyde to give both stable and unstable
    adducts (Tuma et al., 1984).  Several adduct structures, formed when
    acetaldehyde reacts with proteins  in vitro, have been identified,
    but have not yet been described fully.

         The best characterized nucleophiles able to form adducts with
    acetaldehyde are amino groups, notably the alpha-amino terminus of
    peptides and proteins and the epsilon-amino group on the side-chain of
    lysine residues.  These reactions are shown in Fig. 2.

         The structure of 2-methylimidazolidin-4-one adducts has been
    confirmed by proton NMR (Gidley et al., 1981) and 13C-NMR
    spectroscopy (San George & Hoberman, 1986).   N-ethylation lysine
    residues have been demonstrated by Tuma et al. (1984).

         In a series of studies on lysine-dependent enzymes, Mauch et al.
    (1986, 1987) were able to demonstrate that incubation of purified
    enzymes with acetaldehyde for 1 h at 37°C led to inhibition of their
    catalytic activity.  Lysine non-dependent enzymes were not affected by
    this treatment.  A similar study involving the incubation of rat liver
    histone H1 with physiological concentrations of acetaldehyde showed
    that spontaneously stable adducts were formed on lysine residues at
    the carboxy terminus, a site crucial for its function as a eukaryotic
    repressor (Niëmela et al., 1990).  This acetaldehyde-modified histone
    H1 showed impaired DNA binding activity.

         Tuma et al. (1987) have characterized the interaction of
    acetaldehyde with a "highly reactive" lysine residue in purified
    alpha-tubulin, which is only available in the monomeric form.  They
    found that modification of this residue was the critical factor in the
    inhibition of tubulin polymerization by acetaldehyde, and that
    modification of 5% of these residues was enough to inhibit tubulin
    polymerization completely  in vitro.  Crebelli et al. (1989) found
    similar effects: 0.075% v/v (13.5 mmol/litre) acetaldehyde partially
    inhibited the  in vitro polymerization of cattle brain tubulin, and
    0.15% (27 mmol/litre) caused complete inhibition.

         Incubation of calf brain microtubular proteins also resulted in
    decreased polymerization, in an analogous manner to tubulin (McKinnon
    et al., 1987a,b).  Thus, acetaldehyde modification can impair the
    molecular function of macromolecules, which can lead to marked
    alterations in biological function.

    FIGURE 2

         No data are available on the formation of acetaldehydemodified
    proteins in animals or humans directly exposed to acetaldehyde. 
    However, some data are available on proteins modified by acetaldehyde
    derived from ethanol metabolism.  In these studies, proteins carrying
    acetaldehyde adducts were shown to be present in the liver cytosol of
    rats fed ethanol for periods of 3 weeks, 12 months, or 27 months
    (Worrall et al., 1991a). Acetaldehyde-modified proteins have also been
    detected in the plasma (Liu et al., 1990) and haemoglobin of
    alcoholics (Niemela & Israel, 1992).  Furthermore, a limited
    immunohistochemical study has demonstrated the presence of
    acetaldehyde-modified proteins in the livers of some alcoholics
    (Niemela et al., 1991).  These studies demonstrate that acetaldehyde
    adducts can form in the body.  The possible immunological consequences
    of adduct formation will be discussed in section 8.9.

    6.5.2  Nucleic acids

         No data are available from  in vivo studies on the generation of
    DNA adducts.

         Acetaldehyde reacts with nucleosides and deoxynucleosides at pH
    6.5 and 37°C  in vitro to form unstable adducts by binding to the
    exocyclic amino groups of adenine, cytosine, and guanine (Hemminki &
    Suni, 1984).  Addition of a reducing agent (sodium borohydride) leads
    to the formation of stable adducts, of which the main one was
    identified as N2-ethylguanosine using mass spectrometry and NMR.
    Similar data for the formation of unstable adducts formed by reacting
    acetaldehyde with ribonucleosides and deoxyribonucleosides was
    reported by Fraenkel-Conrat & Singer (1988).  When ethanol was present
    in the reaction mixture, a different type of adduct was formed, which
    was identified by fast atom bombardment and proton NMR to be a mixed
    acetal (-NH-CH(CH3)-OR). These adducts were found to have half-lives
    varying from 2.5 to 24 h at pH 7.5 and 37°C, depending on the base


    7.1  Aquatic organisms

         An LC50 (semi-static study) of 35 mg/litre was found for
    acetaldehyde in the guppy (Poecilia reticulata; 10 laboratory-reared
    and acclimatized fish, 2-3 months old) (Deneer et al., 1988).  Grahl
    (1983) reported an LC50 (48-96 h) of 124 mg/litre for acetaldehyde
    in fish (no additional information was provided).  Juhnke & Luedemann
    (1978) presented the results for fish obtained in the Golden Orfe
    test, and found an LC50 of 140-124 mg/litre for acetaldehyde (no
    additional information was provided).  An LC50 (static conditions;
    96-h) of 53 mg/litre was reported for the bluegill  (Lepomis
     macrochirus) by Von Burg & Stout (1991).

         Acetaldehyde had a depressing effect on the aggressive behaviour
    of the fish cichlid  (Cichlasoma nigro fasciatum) at concentrations
    that did not cause locomotor decrements in this species (Peeke &
    Figler, 1981).

         An EC5 (48-h; population growth) of 82 mg/litre and an EC50
    (48-h; static conditions; immobilization) of 42 mg/litre were reported
    for protozoa  (Chilomonas paramecium) and the waterflea  (Daphnia
     magna), respectively (Von Burg & Stout, 1991).

    7.2  Terrestrial organisms

         Aharoni & Barkai-Golan (1973) studied the effects of acetaldehyde
    vapours on the germination and colony-forming potential of two fungi
    species, Alternaria tenuis and Stemphylium botryosum.  The rate of
    growth inhibition increased with both concentration and time of
    exposure.  The exposure of the spores was conducted at room
    temperature.  A. tenuis, the more sensitive species, was inactivated
    by 0.54 µg acetaldehyde/m3 applied for 5 h, whereas 1.08 µg
    acetaldehyde/m3 for 2 h, was needed to inactivate S. botryosum

         Pittevils et al. (1979) reported the activity of acetaldehyde
    against the fungi affecting stored apples and pears  (Colletotrichum
     gloeosporioides, Cryptosporiopsis malicorticis, Phlyctaena
     vagabunda, Botrytis cinerea, and Alternaria tenuis).  Acetaldehyde
    was rapidly lethal at low concentrations: after a 24-h treatment
    period, the lethal concentration of acetaldehyde ranged from
    0.036 µg/m3  (A. tenuis) to 0.09 µg/m3  (C. gloeosporioides).
    Acetaldehyde remained lethal for the five fungi, even when the
    treatment lasted only 20 min (0.90 µg/m3 for  P. vagabunda, C.
     malicorticis, and  A. tenuis, and 0.36 µg/m3 for  C. gloeosporioides
    and  B. cinerea).

         The fungi  Botrytis cinerea, Penicillium expansum, Rhizopus
     stolonifer, Monilinia fructicola, Erwinia carotovora, and
     Pseudomonas fluorescens were killed, when exposed to
    acetaldehyde vapours at concentrations ranging from 0.045 to
    3.6 µg/m3, applied for 0.5 to 120 min at room temperature (Aharoni &
    Stadelbacher, 1973).

         Aharoni et al. (1979) studied acetaldehyde as a fumigant for
    control of the green peach aphid  (Myzus persicae) on head lettuce
     (Lactuca sativa).  When aphids were placed on the lettuce prior to
    fumigation, 0.36 µg acetaldehyde/m3  and a 3-4 h exposure were
    required for 100% mortality.  A similar treatment (0.27-0.36 µg/m3
    for 4 h) was found to cause 100% mortality of aphids on lettuce by
    Stewart et al. (1980).

         The fumigant effect of acetaldehyde was tested on the garden slug
     (Arion hortensis; weight range, 0.2-0.5 g) and the grey field slug
     (Agriolimax reticulatus; weight range, 0.3-0.6 g).  It caused both
    species to close the pulmonary aperture and to secrete excess
    'irritation' mucus.  Medial lethal values of 7.69 ± 0.21 mg/litre
    per h for  A. reticulatus and of 8.91 ± 0.81 mg/litre per h for
     A. hortensis were found (Henderson, 1970).

         The seed germination of the onion  (Allium cepa L.), carrot
     (Daucus carota L.), Palmer Amaranth  (Amaranthus palmeri S Wats.),
    and tomato  (Lycopersicon esculentum Mill.) after exposure to
    acetaldehyde (up to 1.52 mg/litre), was examined by Bradow & Connick
    (1988).  After a 3-day exposure, acetaldehyde inhibited the seed
    germination of all four plants by more than 50%.  Seeds inhibited by a
    3-day exposure to acetaldehyde followed by a 4-day recovery period
    germinated to the same extent as the controls after seven days, except
    for the Palmer Amaranth, which remained inhibited.

         Acetaldehyde at concentrations of 0.54-1.08 µg/m3 affected head
    lettuce  (Lactuca sativa), as evidenced by dark-green, water-soaked,
    necrotic areas on the outer leaves of the lettuce.  Concentrations of
    up to 0.36 µg/m3 did not affect the lettuce (Aharoni et al., 1979;
    Stewart et al., 1980).


    8.1  Single exposure

    8.1.1  LD50 and LC50 values

         Relevant data are summarized in Table 4.

         Oral LD50s for acetaldehyde in rats and mice ranged from 660 to
    1930 mg/kg body weight.  LC50s (0.5-4 h) in rats and Syrian hamsters
    ranged from 24 to 37 g/m3.  It is, therefore, concluded that the
    acute toxicity of acetaldehyde is low.  LD50 values by the dermal
    route were not available.

         LD50s for intratracheal, subcutaneous, intraperitoneal, and
    intravenous administration are also presented in Table 4.

        Table 4.  LD50/LC50 values for acetaldehyde

    Species        Route of                 LD50/LC50                    Reference

    Rat            oral                  1930 mg/kg body weight        Smyth et al. (1951)
    Rat            oral                  660 mg/kg body weight         Sprince et al. (1974)
    Mouse          oral                  1230 mg/kg body weight        US NRC (1977)
    Dog            oral                  > 600 mg/kg body weight       Booze & Oehme (1986)
    Rat            inhalation            24 g/m3; 4 h                  Appelman et al. (1982)
    Rat            inhalation            37 g/m3; 0.5 h                Skog (1950)
    hamster        inhalation            31 g/m3; 4 h                  Kruysse (1970)
    hamster        intratracheal         96.1 mg/kg body weight        Feron & De Jong (1971)
    Rat            subcutaneous          640 mg/kg body weight         Skog (1950)
    Mouse          subcutaneous          560 mg/kg body weight         Skog (1950)
    Mouse          intraperitoneal       500 mg/kg body weight         Truitt & Walsh (1971)
    Mouse          intravenous           165 mg/kg body weight         O'Shea & Kaufman
    (pregnant)                                                         (1979)
    8.2  Short-term exposure

    8.2.1  Oral

         Oral administration in the drinking-water of 675 mg
    acetaldehyde/kg body weight to Wistar rats, daily for 4 weeks,
    resulted in slight to moderate focal hyperkeratosis of the forestomach

    in 8/10 males and 8/10 females.  No effects were observed at lower
    dose levels of 25 and 125 mg/kg body weight.  In the control group,
    very slight focal hyperkeratosis of the forestomach was noted in 6/20
    females and 3/20 males (1/20 slight).  At the top dose (675 mg/kg),
    relative kidney weights were slightly increased in males, urinary
    production was decreased, and there were variations in serum
    biochemistry, most of which were attributable to reduced water intake. 
    There were no effects in the liver.  The no-observed-effect level
    (NOEL) was 125 mg/kg, the lowest-observed-effect level (LOEL) was
    675 mg/kg (Til et al., 1988).

    8.2.2  Inhalation

         Male Sprague-Dawley rats were continuously exposed to
    acetaldehyde vapour for 22 days at levels gradually increasing from
    750 mg/m3 for a few days up to 2500 mg/m3 for the last few days. 
    By gradually increasing the concentrations, mortality in the early
    period following exposure to 2000-2500 mg/m3 was prevented,
    presumably because of metabolic adaptation; sudden, high, blood
    acetaldehyde levels inducing vagal reflex reactions may result in
    respiratory inhibition, and, as a consequence, death (Lamboeuf et al.,
    1987; Latge et al., 1987).

         Groups of 10 male and 10 female Wistar rats were exposed to
    acetaldehyde at 0, 720, 1800, 3950, or 9000 mg/m3 (0, 400, 1000,
    2200, or 5000 ppm) for 6 h/day, 5 days/week, for 4 weeks. Mortality
    was slightly increased at 3950 and 9000 mg/m3, whereas growth was
    retarded at 1800 mg/m3 and above in males, and at 9000 mg/m3 in
    females.  At 9000 mg/m3, relative liver weight decreased, and
    relative lung weight in males increased.  No treatment-related
    histopathological changes were observed in the liver.  Degenerative
    changes of the nose were observed after exposure to all concentrations
    (720 mg/m3-9000 mg/m3), with hyperplasia and metaplasia occurring
    at concentrations of 3950 mg/m3 or more.  A NOEL was not identified
    (LOEL: 720 mg/m3) (Appelman et al., 1982).

         Groups of 10 male Wistar rats were exposed to acetaldehyde, for
    6 h/day, 5 days/week, for 4 weeks, in three different patterns:  (a)
    as a continuous daily exposure of 6 h to 0, 270, or 900 mg/m3 (0,
    150, or 500 ppm),  (b) as two daily exposures of 3 h to similar
    concentrations with an intervening 1.5-h period with no exposure, or
     (c) as two daily 3-h periods of exposure to similar concentrations
    with an intervening 1.5-h period with eight short (5-min) peaks of 6
    times the basic concentration, resulting in time-weighted average
    concentrations of 0, 255, or 1050 mg/m3, respectively.  Though there
    were no indications of toxicity following continuous or interrupted
    exposures to 270 and 900 mg/m3 and intermittent high/low exposure to
    255 mg/m3, intermittent high/low exposure to 1050 mg/m3 induced
    growth retardation (Appelman et al., 1986).

         At 900 mg/m3, the observed effects were very similar to the
    ones reported earlier by Appelman et al. (1982) at 720 mg/m3. 
    Variation of the pattern of exposure, by including a 1.5-h break, or
    by additionally including eight 5-min, 6-fold higher peak exposures,
    did not alter the observed degenerative effects.  No effects were
    observed in Wistar rats exposed to a lower concentration, 5 days/week
    for 4 weeks, either as a "continuous" (6 h/day) exposure of
    270 mg/m3, or as a time-weighted average of 255 mg/m3 after the
    described intermittent low-high exposure.  The NOEL was 255 mg/m3,
    6-h TWA (LOEL = 1050 mg/m3, 6-h time weighted average) (Appelman et
    al., 1986).

         In another study, groups of 12 male Wistar rats were exposed to 0
    or 437 mg acetaldehyde/m3 (0 or 243 ppm), 8 h/day, 5 days per week,
    for 5 weeks.  Hyperplasia of the olfactory epithelium and nasal
    inflammation were observed in exposed animals, and on the basis of
    lung function tests, residual volume and functional residual capacity
    were increased, indicating some (unspecified) damage of the distal
    airways (Saldiva et al., 1985).

    8.2.3  Dermal

         No relevant studies were identified.

    8.2.4  Parenteral

         Effects in the liver have been reported in several studies, but
    only at very high doses.  Intraperitoneal injection of male albino
    rats with 200 mg acetaldehyde/kg body weight, daily, for 10 days, with
    additional pyrazole treatment to inhibit the conversion of
    acetaldehyde to ethanol, caused fatty accumulation in the liver, as
    indicated by accumulation of total lipids, triacyl glycerols, and
    total cholesterol, increased glycogenolysis, and a shift in metabolism
    from the citric acid cycle towards the pentose phosphate pathway in
    the liver.  Serum triacyl glycerol, total cholesterol, and free fatty
    acid levels were also increased.  Changes were similar in rats not
    receiving pyrazole pretreatment (Prasanna & Ramakrishnan, 1984a,
    1987).  The same treatment altered thyroid function, as indicated by
    lower serum T4 and decreased iodine uptake in male albino rats, though
    these effects may have been secondary to the observed hepatic changes
    (Prasanna et al., 1986) and histopathological changes of the pancreas,
    with resulting changes in trypsinogen levels and amylase secretion and
    activity in female Sprague-Dawley rats (Majumdar et al., 1986).

    8.3  Skin and eye irritation; sensitization

         No relevant data were identified.

    8.4  Long-term exposure

    8.4.1  Oral

         In rats exposed to 0.05% acetaldehyde in drinking-water
    (estimated by the Task Group to be approximately 40 mg/kg body weight)
    for 6 months, there was an increase in collagen synthesis in the liver
    (Bankowski et al., 1993).  The toxicological significance of this
    observation is not known; no other effects were examined.

    8.4.2  Inhalation

         Non-neoplastic effects observed in carcinogenicity studies are
    discussed in section 8.7.1.

         Groups of 20 Syrian hamsters were exposed to acetaldehyde vapour
    at 0, 700, 2400, or 8200 mg/m3 (0, 390, 1340, or 4560 ppm) for
    6 h/day, 5 days/week, for 13 weeks.  Increased relative lung and heart
    weights as well as growth retardation were reported after exposure to
    8200 mg/m3, though there were no increases in mortality in any of
    the exposed groups (Kruysse et al., 1975).  At the highest
    concentration, there were severe degenerative, hyperplastic, and
    metaplastic changes in the epithelium as well as subepithelial glands
    and turbinate bones.  Rhinitis was observed, with abundant nasal
    discharge and salivation.  The epithelium of the larynx, trachea, and
    lungs was damaged, with some focal hyperplasia and metaplasia,
    accompanied by tracheitis and focal bronchopneumonia.  Changes in the
    tracheal epithelium were also observed at 2400 mg/m3.  At
    700 mg/m3, no significant effects were observed (NOEL: 700 mg/m3;
    LOEL: 2400 mg/m3).

    8.5  Reproductive and developmental toxicity

         Studies on reproductive effects have not been identified.  A
    number of studies on developmental effects have been conducted,
    primarily to investigate the role of acetaldehyde in ethanol-induced
    teratogenicity.  However, in all of these studies, acetaldehyde was
    administered by injection rather than by the principal routes of
    exposure in the occupational and general environments (i.e., ingestion
    and inhalation).  Results of identified studies in which acetaldehyde
    was administered during gestation to rats and mice by intraperitoneal,
    intravenous, or amniotic injection are presented in Table 5.  Though
    dose-related embryotoxic, fetotoxic, and teratogenic effects were
    observed in most of these studies, particularly those on rats,
    maternal toxicity was not adequately assessed or reported in any of
    these investigations.  Dose-related embryotoxic effects were also
    observed in  in vitro studies on rat embryos exposed to acetaldehyde
    (Popov et al., 1981; Campbell & Fantel, 1983).

         Effects on the placenta have been observed following
    intraperitoneal injection of acetaldehyde into pregnant rats
    (Sreenathan et al., 1984a).  In an  in vitro study on human placental
    membrane vesicles, very high concentrations (approximately 100 times
    higher than the highest reported levels in blood), inhibited L-alanine
    transport (Asai et al., 1985).

    8.6  Mutagenicity and related end-points

         Relevant data are summarized in Table 6.

    8.6.1  Bacteria

         Acetaldehyde was not mutagenic when tested adequately in standard
    preincubation assays with  S. typhimurium.

         Statistically significant mutagenic responses were induced in
     E. coli WP2uvrA in preincubation assays without metabolic activation
    at 37°C (Veghelyi et al., 1978) and 0°C (Igali & Gazso, 1980).  In
    contrast, in another study on the same strain, results were negative
    (Hemminki et al., 1980).

    8.6.2  Non-mammalian eukaryotic systems  Gene mutation assays

         Acetaldehyde (0.1% or 1.0% for 2 h) induced mutations in
    genes that affect the egg-laying system of Caenorhabditis elegans
    (Greenwald & Horvitz, 1980).

         Acetaldehyde induced sex-linked recessive lethal mutations in
     Drosophila melanogaster (Woodruff et al., 1985).  Chromosome alterations

         Acetaldehyde induced chromosome malsegregation and mitotic
    cross-over (yA2 marker) in  Aspergillus nidulans diploid strain P1
    during early conidial germination (Crebelli et al., 1989).

         There was a dose-related increase in chromosomal aberrations in
     Vicia faba root tips exposed to acetaldehyde (Rieger & Michaelis,
    1960).  Acetaldehyde also induced chromosome aberrations, micronuclei,
    and sister chromatid exchanges (SCEs) in the root meristem cells of
     Allium cepa (Cortes et al., 1986).

        Table 5.  Developmental toxicity

    Species    Exposure                   Dose                            Effects                                               Reference

    Rat      day 10, 11, or 12;      0, 50, 75, 100 mg/kg    fetal resorption, malformations (oedema, microcephaly,            Sreenathan
             days 10-12 of           body weight, ip         micrognathia, micromelia, hydrocephaly, exencephaly), growth      et al. (1982,
             pregnancy; days                                 retardation; reduced placental weight; 50 mg/kg body weight,      1984b)
             8-15 (50 mg/kg                                  days 8-15: delays in ossification; skeletal malformations,
             body weight per                                 such as wavy ribs; no discussion of maternal effects

    Rat      days 8-15 of            50, 75, 100 or 150      increase in resorption, and fetal death (changes were dose        Padmanabhan
             pregnancy               mg/kg body weight,      dependent); malformations: oedema, microcephaly, micrognathia,    et al. (1983)
                                     ip                      micromelia, syndactyly, hydronephrosis and subcutaneous
                                                             haemorrhage in the face, fore- and hind paws; reduced mean
                                                             placental weight and umbilical cord length; increased amniotic
                                                             fluid weight
                                                             maternal toxicity: rel. reduced water, food consumption, rel.
                                                             reduced body weight gain, 50 mg and above

    Rat      day 13 of pregnancy     1% or 10% solution      10%: 100% mortality; 1%: 80% malformations versus 14% in          Bariliak &
    embryo                           amniotic injections     controls                                                          Kozachuk

    Rat      days 9-12 of pregancy   1% (100 mg/kg body      reduction in head length; no effects on morphological             Ali &
                                     weight), ip             scores or crown rump length                                       Persaud (1988)

    Table 5 (contd).

    Species    Exposure                   Dose                            Effects                                               Reference

    Rat      days 8-13 of            10 or 50 mg/kg body     reduced performance in surface righting, olfactory                Schreiner
             pregnancy               weight, ip              discrimination, and learning ability; lower startle amplitudes    et al. (1987)
                                                             in an auditory startle habituation test; maternal toxicity not    Abstract
                                                             addressed; age of testing of offspring not specified

    Rat      day 5 of gestation      0.03-0.04 µg/kg body    retarded blastulation                                             Checiu et
                                     weight examination on                                                                     al. (1984)
                                     day 5 of gestation

    Mouse    day 7 or 8 of           0.32 g/kg, iv           exencephaly, mandibular and maxillary hypoplasia;                 Webster et
             pregnancy; day 9                                polydactyly club foot; no discussion of maternal effects          al. (1983)
             or 10 of pregnancy

    Mouse    day 10 of pregnancy     1000 mg/kg, ip          no increase in resorptions or malformed fetuses or decrease       Blakley &
                                                             in fetal weight; no discussion of maternal effects                Scott (1984a)

    Mouse    day 7, 8 or 9 of        31 or 62 mg/kg body     dose-dependent embryolethality; non-closure of anterior or        O'Shea &
             pregnancy               weight, iv;             posterior neuropore; smaller embryos; no discussion of            Kaufman
                                     examination on day      maternal effects                                                  (1979)
                                     10 or 19 of gestation

    Mouse    day 9 of pregnancy      2, 4, 6% (8 ml/kg       no intermediate cellular effeects                                 Bannigan &
                                     body weight), ip                                                                          Burke (1982)

    Mouse    day 6, 7 or 8 of        62 mg/kg body weight,   neural tube effects; embryonic mortality; no discussion           O'Shea &
             pregnancy; and days     iv; examination on      of maternal effects                                               Kaufman
             6-8, 7-8 or 7-9 of      day 10 or 12 of                                                                           (1981)
             pregnancy               gestation

    Table 6.  Tests for gene mutation, chromosomal damage, and sister chromatid exchanges induced by acetaldehyde

    Test system                Measured end-point            Test conditions                          MA      RES        Reference

    Prokaryotic systems

    Escherichia coli WP2uvrA   reverse mutations           40 µg/ml; preincubated in capped tubes      -      +      Veghelyi et al. (1978)

    Escherichia coli WP2uvrA   reverse mutations           0.88-441 µg/ml; incubated in capped         -      -      Hemminki et al. (1980)
                                                           tubes at 37°C

    Escherichia coli Wp2uvrA   reverse mutations           0.8 µg/ml; incubated in capped tubes        -      +      Igali & Gazso (1980)
                                                           at 0°C

    Salmonella typhimurium
    TA102                      reverse mutations           1014 µg/plate; liquid preincubation         -      -      Marnett et al. (1985)
    TA104                                                                                                     -

    Salmonella typhimurium     reverse mutations           33-10 000 µg/plate; liquid preincubation    +      -      Mortelmans et al. (1986)
    TA1535                                                                                             -      -
    TA1537                                                                                             +      -
                                                                                                       -      -
    TA97                                                                                               +      -
                                                                                                       -      -
    TA98                                                                                               +      -
                                                                                                       -      -
    TA100                                                                                              +      -
                                                                                                       -      -

    Table 6 (contd).

    Test system                Measured end-point            Test conditions                          MA      RES        Reference

    Salmonella typhimurium     concentration not given;                                                +      -      Sasaki & Endo (1978)
    TA100                      liquid preincubation

    Non-mammalian eukaryotic systems

    Allium cepa root           chromosomal aberration      7.5-7500 µg/ml                              -      +      Cortés et al. (1986)
    meristem cells             and SCE                                                                        +

    Vicia faba root tips       chromosomal aberration      220-2205 µg/ml for 24 h at 12°C             -      +      Rieger & Michaelis (1960)

    Caenorhabditis elegans     gene mutation               794-7940 µg/ml for 2 h                      -      +      Greenwald & Horvitz

    Drosophila melanogaster    sex-linked recessive        22 500 mg/litre in 10% ethanol by                  +      Woodruff et al. (1985)
    Canton-S wild-type         lethal mutations            25 000 mg/litre in 10% ethanol by                  -

    Aspergilus nodulans        chromosomal                 198-2381 µg/ml                                     +      Crebelli et al. (1989)
    Diploid P1                 malsegregation

    In vitro mammalian systems

    Mouse lymphoma L5178Y      forward mutation (tk        176-353 µg/ml for 4 h                       -      +      Wangenheim & Bolcsfoldi
    cells                      locus)                                                                                (1986, 1988)

    Chinese hamster ovary      chromosomal aberration      88-5000 µg/ml                               -      +      Au & Badr (1979)

    Table 6 (contd).

    Test system                Measured end-point            Test conditions                          MA      RES        Reference

    Chinese hamster ovary      SCE                         1.3-13 µg/ml                                -      +      Brambilla et al. (1986)

    Chinese hamster ovary      SCE                         8-80 µg/ml for 1 h                          +      +      De Raat et al. (1983)
    cells                                                                                              -      +

    Chinese hamster ovary      SCE                         2-12 µg/ml for 24 h                         -      +      Obe & Beek (1979)

    Chinese hamster ovary      SCE                         4-8 µg/ml for 8 days                        -      +      Obe & Ristow (1977)

    Chinese hamster ovary      hyperploidy                 0.35-1.05 mmol/litre                        -      +      Dulout & Furnus (1988)
    cells                      hypoploidy                                                                     +

    Human lymphocytes          forward mutations           26.5-106 µg/ml for 24 h                     -      +      He & Lambert (1990)
                               (hprt locus)                8.8-26.5 µg/ml for 48 h

    Human lymphocytes          chromosomal aberration      0.1-20 mmol/litre added                            +      Obe et al. (1985)
                               every 12 h for 5 days

    Human lymphocytes          chromosomal aberration      8-15 µg/ml                                  -      +      Obe et al. (1979)
                               (normal Franconis

    Table 6 (contd).

    Test system                Measured end-point            Test conditions                          MA      RES        Reference

    Human lymphocytes          chromosomal aberration      0.8 µg/ml 2x/day, 4 days                    -      +      Obe et al. (1978)

    Human lymphocytes          chromosomal aberration      4-48 µg/ml for 72 h                         -      +      Boehlke et al. (1983)
                               SCE                                                                            +

    Human (whole blood,        chromosomal aberration      20-40 µg/ml                                        +      Badr & Hussain (1977)

    Human lymphocytes          SCE                         4.4-106 µg/ml for 1-70 h                    -      +      He & Lambert (1985)

    Human lymphocytes          SCE                         4.4-13 µg/ml for 70 h                       -      +      Lambert & He (1988)

    Human lymphocytes          SCE                         4.4-18 µg/ml for 72 h                              +      Helander & Lindahl-
                                                                                                                     Kiessling (1991)

    Human lymphocytes          SCE                         4.4-22 µg/ml for 48 h                              +      Sipi et al. (1992)

    Human lymphocytes          SCE                         4-8 µg/ml for 90 h                          -      +      Jansson (1982)

    Human lymphocytes          SCE                         0.04-4.4 µg/ml for 55 h                     -      +      Knadle (1985)

    Human lymphocytes          SCE                         5.5-88 µg/ml for 48 h                       -      +      Norppa et al. (1985)

    Human lymphocytes          SCE                         reaction mixture added to whole blood       -      +      Obe et al. (1986)
                                                           samples in dialysis tube;                   +      +
                                                           concentration not given

    Human lymphocytes          SCE                         4-16 µg/ml for 24 h                         -      +      Ristow & Obe (1978)

    Table 6 (contd).

    Test system                Measured end-point            Test conditions                          MA      RES        Reference

    Human lymphocytes          chromosomal aberration      1.8-35 µg/ml for 72 h                       -      +      Véghelyi & Osztovics

    Human lymphocytes          SCE                         1.8-35 µg/ml for 72 h                              +      Véghelyi et al. (1978)

    Wistar rat (skin           chromosomal aberration      4.4-44 µg/ml for 12, 24, or 48 h            -      +      Bird et al. (1982)
    fibroblast)                (micronuclei)

    Mouse embryo               cell transformation         10-100 µg acetaldehyde/ml for 24 h          -      -      Abernethy et al. (1982)
    C3H/10T1/2 cells                                       10-100 µg/ml followed by 0.25 µg                   +
                                                           TPA/ml 2x/week

    Rat (HRRT kidney cells)    cell transformation         acetaldehyde                                -      -      Eker & Sanner (1986)
                                                           acetaldehyde followed by TPA and PDD               +

    MA = Metabolic activation; RES = Result.

    8.6.3  Cultured mammalian cells  Gene mutation assays

         Acetaldehyde induced gene mutations at the hypoxanthineguanine
    phosphoribosyl transferase (hprt) locus in human lymphocytes
     in vitro; there was a statistically significant and dose-related
    increase in the frequency of mutants (He & Lambert, 1990). 
    Acetaldehyde produced a significant dose-related increase in forward
    mutations in a mouse lymphoma L5178Y thimidine kinase locus assay,
    without exogenous metabolic activation (Wangenheim & Bolcsfoldi, 1986,
    1988).  Chromosome alterations and sister chromatid exchange

         Dose-dependent increased frequencies of chromosome aberrations
    have been observed in human lymphocytes following incubation with
    acetaldehyde (Badr & Hussain, 1977; Obe et al., 1978, 1979, 1985;
    Veghelyi & Ostovics, 1978; Boehlke et al., 1983).

         Acetaldehyde induced a dose-dependent increase in chromosomal
    damage in Chinese hamster ovary cells, though it was reported that the
    activity was reduced (not quantified) in the presence of liver
    homogenate fraction (Au & Badr, 1979).  Dose-related increases in
    micronuclei and chromosome aberrations were observed in cultured rat
    skin fibroblasts in the absence of metabolic activation (Bird et al.,

         SCE was induced by acetaldehyde (1.3-106 µg/ml) in the absence of
    exogenous metabolic activation in Chinese hamster ovary cells and
    human lymphocyte cultures (Obe & Ristow, 1977; Ristow & Obe, 1978;
    Veghelyi et al., 1978; Veghelyi & Osztovics, 1978; Obe & Beek, 1979;
    Jansson, 1982; Boehlke et al., 1983; De Raat et al., 1983; He &
    Lambert, 1985; Knadle, 1985; Norppa et al., 1985; Brambilla et al.,
    1986; Obe et al., 1986; Lambert & He, 1988; Helander &
    Lindahl-Kiessling, 1991; Sipi et al., 1992).  The increase in SCEs in
    Chinese hamster ovary cells was less pronounced after addition of an
    exogenous metabolic activating system (De Raat et al., 1983). 
    Similarly, addition of NAD+ and ALDH to human lymphocyte cultures
    exposed to acetaldehyde decreased SCE induction (Obe et al., 1986). 
    Addition of 1-amino-cyclopropanol, an inhibitor of ALDH, to human
    lymphocytes enhanced SCE induction by acetaldehyde (Helander &
    Lindahl-Kiessling, 1991).  These observations suggest that ALDH may
    reduce the genotoxic potential of acetaldehyde.

         Acetaldehyde induced aneuploidy has been reported in Chinese
    hamster ovary cells (Dulout & Furnus, 1988).  However, mainly
    hypoploid cells were increased and, therefore, no firm conclusion can
    be drawn from these studies.  Acetaldehyde induced SCE in
    pre-implantation mouse embryos  in vitro (Lau et al., 1991).

    8.6.4  In vivo assays

         Only limited data are available on the genotoxicity of
    acetaldehyde  in vivo.  Somatic cells

         C57BL/6J mice (only 2 animals of unspecified sex at each dose
    level) received daily intraperitoneal doses of 0, 6, or 12 mg
    acetaldehyde/kg body weight per day, for 5 days, and blood samples
    were collected on days 3-6.  The frequencies of micronuclei in mature
    peripheral erythrocytes on days 5 and 6 (combined) were significantly
    increased at the low dose, but not at the high dose (Ma et al., 1985). 
    No information on the frequency in polychromatic erythrocytes was
    provided, so the possibility that this result was due to increased
    erythropoiesis instead of mutagenesis cannot be discounted.  This
    study was reported only in the form of an abstract.

         Groups of 6-7 Chinese hamsters (male and female) received 0.01,
    0.1, or 0.5 mg acetaldehyde/kg body weight in saline by single
    intraperitoneal injection and were killed 24 h later.  Doses of
    0.6 mg/kg body weight were lethal in preliminary tests.  The
    frequencies of SCEs in bone-marrow metaphases were elevated at 0.5 mg
    acetaldehyde/kg body weight, but not at the lower doses (Korte & Obe,
    1981).  These observations support earlier findings in a more limited
    study at an embryotoxic dose in mice and indicate  in vivo formation
    of SCEs (Obe et al., 1979).

         Female Wistar rats were injected with 0.02 ml of 1% acetaldehyde
    intra-amniotically on day 13 of pregnancy. Embryonic cells were
    obtained 24 h later for cytogenetic analysis.  Exposed rat embryos had
    a higher frequency of chromosomal aberrations (mostly chromatid gaps
    and breaks) than controls (Barilyak & Kozachuk, 1983).  There was no
    increase in the frequency of aneuploid cells.  Germ cells

         Hybrid male mice ((C57B1/6J × C3H/He)F1), 4/dose group, were
    injected intraperitoneally with a single dose of 0, 125, 250, 375, or
    500 mg acetaldehyde/kg body weight in saline.  Thirteen days after
    exposure, the frequency of micronuclei in early spermatids was not
    increased, though there were adequate positive controls (Lahdetie,

    8.6.5  Other assays

         Relevant data are summarized in Table 7.  DNA single-strand breaks

         No single-strand breaks were detected with the alkaline elution
    assay in DNA from various sources, after exposure  in vitro to
    acetaldehyde (Sina et al., 1983; Marinari et al., 1984; Harris et al.,
    1985; Lambert et al., 1985; Saladino et al., 1985).  DNA cross-linking

         There is some indirect evidence suggesting DNA cross-linking by

         Ristow & Obe (1978) observed enhanced reannealing of heat
    denatured, isolated, calf thymus DNA following incubation with
    acetaldehyde.  It was suggested that this may have been due to DNA-DNA
    cross-linking, because thermally denatured DNA will not reanneal in
    this assay, unless complimentary DNA strands are held together by

         Altered alkaline elution patterns indicative of DNA-DNA
    cross-links were observed with DNA isolated from cultured human
    leukocytes and exposed initially to acetaldehyde and then to X-rays
    (Lambert et al., 1985; Lambert & He, 1988).  DNA-protein cross-linking
    was not observed by Harris et al. (1985) or by Saladino et al. (1985)
    after exposure of human bronchial epithelial cells  in vitro, but it
    was observed by Lam et al. (1986) after incubation of either calf
    thymus nucleohistones or fresh homogenates of the nasal mucosa of rats
    with acetaldehyde.  The possibility that acetaldehyde induces
    DNA-protein cross-links in male Fischer-344 rat nasal mucosa has been
    indirectly studied by measuring the extractability of DNA from
    insoluble proteins following  in vitro and  in vivo exposures. 
    Decreased extractability of DNA was observed in preparations from
    tissue homogenates exposed to acetaldehyde at concentrations of 100
    and 500 mmol per litre but not 10 mmol/litre.  Similarly, decreased
    extractability was observed in nasal mucosal preparations from rats
    exposed for 6 h to 1000 or 3000 mg/litre (ppm) but not 100 or
    300 mg/litre (ppm) (Lam et al., 1986).

        Table 7.  Other tests indicative of genetic damage induced by acetaldehyde

    Test system                     Measured end-point           Test conditions              Results        Reference

    Calf thymus DNA                DNA-DNA cross-links           44 100 µg/ml for 30 min         +          Ristow & Obe (1978)

    Calf thymus nucleohistones     DNA-protein cross-links       4410-44 100 µg/ml               -          Lam et al. (1986)

    Chinese hamster ovary          DNA single-strand breaks      no details                      -          Marinari et al. (1984)
    K1-cells                       DNA-DNA cross-links                                           +

    Rat hepatocytes                DNA single-strand breaks      1.3 µg/ml for 3 h               -          Sina et al. (1983)

    Human bronchial epithelial     DNA single-strand breaks      unknown concentration;          -          Harris et al. (1985)
    cells                          DNA-protein cross-links       6 h                             -

    Human bronchial epithelial     DNA single-strand breaks      up to 44 µg/ml for 1 h          -          Saladino et al. (1985)
    cells                          DNA-protein cross-links                                       -

    Human leukocytes               DNA single-strand breaks      441-882 µg/ml for 4 h           -          Lambert et al. (1985)
                                   DNA-DNA cross-links                                           +

    Human lymphocytes              DNA-DNA cross-links           441 µg/ml                       +          Lambert & He (1988)


    8.6.6  Cell transformation

         Acetaldehyde did not initiate cell transformation in cultured
    C3H/10T1/2 cells in the presence of the tumour promotor
    12- O-tetradecanoylphorbol-13-acetate (TPA) (Abernethy et al., 1982).

         Acetaldehyde initiated cell transformation in a rat kidney cell
    line (HRRT) after pretreatment with tumour promotors (Eker & Sanner,

    8.7  Carcinogenicity bioassays

    8.7.1  Inhalation exposure

         Only one carcinogenicity study in which animals were exposed by
    inhalation to acetaldehyde over a lifetime has been performed.  In
    other carcinogenicity bioassays, animals were exposed for shorter

         Wistar rats (55/sex per dose) were exposed for life (6 h/day, 5
    days/week, for 28 months) to acetaldehyde concentrations of 1350,
    2700, or 1800-5400 mg/m3 (the last concentration was gradually
    reduced from 5400 mg/m3 in week 20 to 1800 mg/m3 in week 52). 
    Satellite groups of 5-10 additional rats of each sex were killed at
    13, 26, and 52 weeks.  Growth retardation occurred throughout the
    study at all dose levels.  Mortality was greater than in controls in
    all dose groups and all of the animals in the high-dose group had died
    by week 102.  At week 52, there were degenerative changes in the
    olfactory nasal epithelium at all dose levels including slight to
    severe hyperplasia and keratinized stratified metaplasia of the larynx
    (high dose only) and degenerative changes of the upper respiratory
    epithelium (including papillomatous hyperplasia at the top dose only). 
    In the trachea, there was focal flattening and irregular arrangement
    of the epithelium in 3/10 top-dose males at 52 weeks.  In satellite
    groups of 30 rats per sex, for which there was a 26-week recovery
    period after 52 weeks of exposure, there was evidence of partial
    regeneration of the olfactory epithelium in the low- and mid-dose
    groups; there was also progression from hyperplasia and metaplasia to
    neoplasia in some animals.  At 28 months, carcinomas of the nose
    developed in all exposed groups (Table 8).  Although tumour incidence
    was dose-related, the latency period appeared to be independent of
    concentration.  First tumours in all groups appeared during the 12th
    month of exposure.  The incidence of tumours was not increased in the
    lungs, larynx, and trachea.

         In simultaneously exposed groups of 30 Wistar rats/sex per dose,
    exposure was terminated after 52 weeks and the animals killed
    following a recovery period of 26 weeks.  After the recovery period,
    both mortality and nasal tumour incidence were very similar to those
    in the groups in which exposure had been continued for 26 more weeks
    (Woutersen et al., 1984, 1986; Woutersen & Feron, 1987).

         Groups of Syrian golden hamsters (36/sex per dose) were exposed
    for 52 weeks (7 h/day, 5 days/week) to a concentration gradually
    reduced from 4500 mg/m3 in week 9 to 2970 mg/m3 in week 52.  At
    week 52, six animals/sex per dose were killed; the remaining animals
    (30/sex per dose) were killed after a recovery period of 29 weeks.  At
    the end of the recovery period, nasal carcinomas were observed in 1/26
    males and 1/27 females versus 0/24 and 0/23 in controls, and the
    incidence of laryngeal carcinomas was increased (5/23 in males, 3/20
    in females, against 0/20 and 0/22 in controls).  No tumours were
    observed in bronchi or lungs (Feron et al., 1982).

    Table 8.  Incidence of nasal tumours in Wistar rats after 28 months
              of exposurea,b

    Types of tumour             0          1350        2700        2760c
                               mg/m3      mg/m3       mg/m3       mg/m3


    Squamous cell carcinoma     1/49      1/52        10/53*      16/49***
    Adenocarcinoma              0/49      16/52***    31/53***    21/49***
    Carcinoma in situ           0/49      0/52        0/53        1/49


    Squamous cell carcinoma     0/50      0/48        5/53        17/53***
    Adenocarcinoma              0/50      6/48*       28/53***    23/53***
    Carcinoma in situ           0/50      0/48        3/53        5/53

    a  From: Woutersen et al. (1986).
    b  Total number of tumour-bearing animals not specified.
       Significance: Fisher Exact Test *P < 0.05, **P < 0.01, ***P <
    c  The highest concentration was gradually reduced from
       5400 mg/m3 during the first 20 weeks to 1800 mg/m3 in week
       52; the time-weighted average concentration for 28 months of
       exposure was calculated by the Task Group to be 2760 mg/m3.

         Groups of 35 male Syrian hamsters were exposed by inhalation to 0
    or 2700 mg acetaldehyde/m3 (0 or 1500 ppm) for 7 h/day, 5 days/week
    for 52 weeks.  At 52 weeks, 5 animals were killed for pathological
    examination.  The remainder of the animals were maintained for a
    further 26-week recovery period.  Body weight gain was less in the
    exposed animals and mortality was increased from week 52 onwards.

    There was a slight, but significant, decrease in rbc, haemoglobin, and
    haematocrit in exposed animals.  Relative kidney weights were
    increased and urinary levels of protein and GOT were elevated.  There
    were marked lesions in the nasal cavity of animals killed at 52 weeks:
    flattened epithelial cells with bizarre nuclei, fewer subepithelial
    glands, submucosal thickening, and keratinizing stratified squamous
    metaplasia of olfactory and respiratory epithelium.  There was also
    slight focal hyperplasia and metaplasia of the epithelium of the
    trachea.  There was partial or complete recovery from these lesions in
    the animals killed at the end of the recovery period.  There were no
    tumours of the respiratory tract in any of the animals exposed to
    acetaldehyde (Feron, 1979).

         Weekly intratracheal administration of 0.2 ml of 2 or 4%
    acetaldehyde in saline during a period of 52 weeks, followed by a
    recovery period of another 52 weeks, did not induce any tumours in the
    respiratory tract of male and female Syrian golden hamsters (Feron,

    8.7.2  Co-carcinogenicity and promotion studies

         In a mid-term test (Ito Model), groups of 19-20 male F344 rats
    received a single intraperitoneal injection of diethylnitrosamine and
    then various concentrations of acetaldehyde (2.5% and 5%, associated
    with a recorded daily intake of 1.66 and 2.75 mg/kg body weight) in
    their drinking-water, from week 2 until termination in week 6.  All
    rats had a two-thirds partial hepatectomy in week 3, in order to
    stimulate cell proliferation.  At 6 weeks, there was a significant
    decrease in liver and body weight in all exposed animals, but
    acetaldehyde had no effect on the development of glutathione
     S-transferase (placental type)-positive liver cell foci (Ikawa et
    al., 1986).

         There were laryngeal tumours in 7/31 male and 6/32 female Syrian
    golden hamsters exposed to a mixture of isoprene (approximately
    2.09 mg/m3 or 750 ppm), methyl chloride (approximately 1.94 mg/m3
    or 950 ppm) methyl nitrite (approximately 0.49 mg/m3 or 195 ppm) and
    acetaldehyde (approximately 2340 mg/m3 or 1300 ppm) for 6 h/day, 5
    days/week, over 23 months.  There were no tumours of the respiratory
    tract in controls (Feron et al., 1985).  The authors suggested that
    the laryngeal effects observed in hamsters exposed to the vapour
    mixture were most probably caused by acetaldehyde alone (presumably
    based on comparison with results in studies on hamsters exposed to
    acetaldehyde alone).

         There was no evidence of co-carcinogenicity in Syrian golden
    hamsters exposed either by simultaneous inhalation exposure to
    acetaldehyde and intratracheal instillation of benzo(a)pyrene (Feron,
    1979; Feron et al., 1982) or by intratracheal instillation of
    diethylnitrosamine (Feron et al., 1982) for 52 weeks followed by

    recovery periods of 26-28 weeks.  Nor was there any evidence of the
    co-carcinogenicity of acetaldehyde following simultaneous
    intratracheal instillations of acetaldehyde and either benzo (a)pyrene
    or diethylnitrosamine for 52 weeks, followed by a recovery period of
    52 weeks (Feron et al., 1982).

    8.8  Neurological effects

         Secondary effects of acetaldehyde on the respiratory and
    cardiovascular systems, attributed to its influence on the autonomic
    nervous system, have been observed following acute exposure of
    experimental animals to acetaldehyde, principally by infusion or
    intravenous administration.  In two identified studies in which
    animals were exposed by a route more relevant to environmental or
    occupational exposure (i.e., inhalation), a 50% decrease in
    respiratory rate was observed in two strains of mice and in rats
    during inhalation of 5000 mg/m3 for 10 min (Steinhagen & Barrow,
    1984; Babiuk et al., 1985; Takahashi et al., 1986).

         Neurological effects following exposure by routes most relevant
    to environmental and occupational exposure (i.e., inhalation and
    ingestion) were limited to biochemical changes in the brain in
    short-term studies on rats and mice exposed to relatively high
    concentrations of acetaldehyde (750-13 230 mg/m3). Reported effects
    included changes in the phospholipid fractions and increases in the
    concentrations of monoamines and Na+/K+ATPase (Ortiz et al., 1974;
    Shiohara et al., 1985; Latge et al., 1987; Roumec et al., 1988). 
    Manifestations of neurotoxicity were not examined in any of these

         In the only identified study in which histopathological effects
    on the nervous system were reported, degeneration was observable using
    both light and electron microscopy in the cerebral cortex of rats
    receiving a single intraperitoneal injection of 5 mg acetaldehyde/kg
    body weight (Phillips, 1987).

         In a short-term study involving intravenous exposure (24-26 mg/kg
    body weight per day, for 20 days), the level of salsolinol in the
    brain of rats was increased (Myers et al., 1985).  Biochemical effects
    of acetaldehyde on the brain have also been observed  in vitro in
    cerebral cortical neurons and brain microsomal preparations (Lahti &
    Majchrowicz, 1969; Cederbaum & Rubin, 1977; Kuriyama et al., 1987).

    8.9  Immunological effects

    8.9.1  Direct effects on immune cells

         Only one study has been carried out on whole animals.  In a study
    on CD1 mice exposed to 324 mg/m3, 3 h/day for 5 days, the
    bacteriocidal activity of alveolar macrophages was reduced by 15%. 
    However, acetaldehyde did not affect mortality following streptococcal
    infection (Aranyi et al., 1986).

         In  in vitro studies, 0.01% acetaldehyde caused a significant
    inhibition of human granulocyte chemotaxis (Schopf et al., 1985).  At
    0.03%, acetaldehyde inhibited the release of lysozyme from monocytes,
    but granulocytes were unaffected.  The generation of oxygen radicals
    by zymosan particle-stimulated monocytes and granulocytes was
    inhibited by acetaldehyde in a dose-dependent manner.  In a similar
    study in which peripheral mononuclear cells were incubated with
    acetaldehyde, decreased lytic activity against K562 cells was observed
    at concentrations higher than 12 µmol per litre (Fink & Dancygier,
    1988).  In another study, acetaldehyde decreased 3H thymidine
    incorporation into phytohaemagglutinin or Concanavalin A - stimulated
    human lymphocytes (Levallois et al., 1987).

    8.9.2  Generation of antibodies reacting with acetaldehyde-modified

         The modification of proteins has been described in section 6.5.1. 
    In several studies, these modified proteins induced an immune response
    when injected into rabbits and mice (Israel et al., 1986; Worrall et
    al., 1989).  The reactivity of the resulting antibodies towards
    proteins, modified by acetaldehyde  in vitro, is independent of the
    carrier protein.  These studies demonstrate  (a) that
    acetaldehyde-modified proteins are immunogenic; and  (b) that
    antibodies raised against a single modified protein will cross-react
    with any other protein modified in the same manner.

         Passive immunization of rats with a monoclonal IgE
    antiacetaldehyde adduct antibody, derived from mice immunized with
    acetaldehyde-modified proteins, rendered these animals hypersensitive
    to acetaldehyde-modified proteins (Israel et al., 1992).

         No immunization studies analogous to those described above have
    been carried out on humans.  In several studies, the presence of
    antibodies, reactive with proteins modified by acetaldehyde  in vitro,
    has been reported in the plasma of alcoholics (Niemela et al., 1987;
    Hoerner et al., 1988; Worrall et al., 1990, 1991a,b).  The results of
    these studies suggest that acetaldehyde-modified proteins are
    generated in humans.

    8.9.3  Related immunological effects

         In rat liver membrane vesicles, exposed to acetaldehyde  in vitro,
    superoxide anion production by neutrophils was significantly enhanced
    (Williams & Barry, 1986).  In a further study, human liver plasma
    membranes, modified by acetaldehyde, activated complement protein C3
    components (Barry & McGivan, 1985).

    8.10  Biochemical effects

         Biochemical effects have been observed in cultured hepatocytes,
    liver homogenates and mitochondrial fractions, purified enzymes,
    isolated hepatic lipid membranes and whole liver preparations,
    including: metabolic effects on lipid peroxidation (Stege, 1982;
    Mueller & Sies, 1987; Shaw & Jayatilleke, 1987), phospholipid
    metabolism (Snyder, 1988), transaminase activity (Solomon, 1987;
    Snyder, 1988), carbohydrate and lipid metabolism (Matsuzaki & Lieber,
    1977; Cederbaum & Dicker, 1981), and mitochondrial respiration
    (Cederbaum et al., 1974).  Increased hepatic collagen synthesis has
    also been observed (Savolainen et al., 1984; Brenner & Chojkier,

         Metabolic effects have been observed in other  in vitro systems
    including: renal cortex tubules (Michoudet & Baverel, 1985: altered
    pyruvate/lactate metabolism), kidney, and muscle microsomal
    preparations (Cederbaum & Rubin, 1977: inhibition of pyruvate
    dehydrogenase), perfused hearts and cardiac whole homogenates
    (Schreiber et al., 1972, 1974: myocardial protein synthesis and
    inhibition of cardiac microsomal protein synthesis; Rawat, 1979:
    reduced protein synthesis; Segel, 1984: no effect on mitochondrial
    respiration), myocardial cells (McCall & Ryan, 1987: no effect on
    Na+/K+-ATPase), leukocytes (Green & Baron, 1986: inhibition of
    Na+/K+-ATPase), erythrocytes (Helander & Tottmar, 1987: inhibition
    of the disappearance rate of biogenic aldehydes; Ninfali et al., 1987:
    induction of intracellular reduced state; Solomon, 1988: inhibition of
    aldolase-mediated by acetaldehyde oxidation- and inhibition of the
    aminotransferases-mediated by non-oxidative acetaldehyde
    metabolization; Atukorala et al., 1988: inhibition of transketolase),
    and leukocytes and platelets (Helander & Tottmar, 1987: inhibition of
    the disappearance rate of biogenic aldehydes).


    9.1  General population exposure

         No specific studies were available.

    9.2  Occupational exposure

    9.2.1  General observations

         Acute exposure to acetaldehyde vapours has resulted in irritation
    of the eyes and mucous membranes, reddening of the skin, pulmonary
    oedema, headache, and sore throat.  Repeated exposure causes
    dermatitis and conjunctivitis.  Ingestion causes nausea, vomiting,
    diarrhoea, narcosis, and respiratory failure.  Liquid acetaldehyde was
    reported to cause superficial injury of the cornea.  These effects
    were reported in reviews and not in documented studies (Grant, 1974;
    Hagemeyer, 1978; Dreisbach, 1987).  In addition, a statement was found
    in a textbook stating that prolonged exposure to acetaldehyde caused a
    decrease in red and white blood cells plus a sustained rise in blood
    pressure; however, no further information was available (Hagemeyer,

    9.2.2  Clinical studies

         A group of 12 volunteers were exposed in a chamber to various
    nominal concentrations of acetaldehyde vapour on 15 different
    occasions.  No atmospheric sampling was performed.  At 90 mg/m3
    (50 ppm), the majority of the group experienced some degree of eye
    irritation.  Several subjects were discomforted at a lower
    concentration of 45 mg/m3 (25 ppm), but no details were provided
    (Silverman et al., 1946).

         A group of 14 "healthy male" volunteers, aged 18-45 years, were
    exposed in a 100 m3 chamber to a measured concentration of
    acetaldehyde vapour of 240 mg/m3 (134 ppm) for 30 min.  This
    concentration was said to be mildly irritating to the upper
    respiratory tract.  No other clinical signs were reported (Sim &
    Pattle, 1957).

         Twelve volunteers of Oriental ancestry were patch-tested with
    acetaldehyde (75%), ethanol (75%), and ethyl acetate (25%).  With
    acetaldehyde treatment, cutaneous erythema was seen in all 12
    subjects, whereas ethanol was positive in 5 subjects.  No vascular
    response was detected for the acetaldehyde metabolite, ethyl acetate
    (Wilkin & Fortner, 1985).

         In an additional study, increased heart rate, ventilation, and
    calculated respiratory dead space, and a decrease in alveolar CO2
    levels were reported, following intravenous infusion of acetaldehyde
    (5% v/v) in young male volunteers (Asmussen et al., 1948).

    9.2.3  Epidemiological studies

         A very limited investigation was performed on an unspecified
    number of people, selected from 150 workers who had been employed for
    20 years or more in a chemical factory.  Nine cases of cancer were
    identified (all in male smokers) 5 of which were in the respiratory
    tract, 2 in the oral cavity, 1 in the stomach, and 1 in the caecum. 
    The number of respiratory cancers was higher than expected compared
    with the prevalence in the national population (not corrected for
    smoking).  In parts of the factory, there was exposure to a variety of
    chemicals. In one area, 1-7 mg acetaldehyde/m3 had been measured,
    together with 5-70 mg butyraldehyde/m3, 1-7 mg crotonaldehyde/m3,
    2-6 mg  n-butanol per m3, and about 15 mg ethylhexanol/m3.  Other
    areas of the factory were known to have higher concentrations of
    vapours of aldehydes and aldol, which caused irritation of the eyes
    and upper respiratory tract (Bittersohl, 1974, 1975).

    9.3  Effects of endogenous acetaldehyde

    9.3.1  Effects of ethanol possibly attributable to acetaldehyde or
           acetaldehyde metabolism

         There is no direct evidence to link acetaldehyde with liver
    injury.  However, data obtained from animal models and human subjects
    suggest that acetaldehyde may play a role in liver damage, especially
    that associated with ethanol (sections 3.1.1 and 8.10).

         An increased sensitivity to ethanol with respect to facial
    flushing was observed in certain human populations (especially of
    Oriental origin), which was ascribed to genetic differences in
    acetaldehyde elimination, due to aldehyde dehydrogenase polymorphism
    (Goedde & Agarwal, 1986, 1987; Eriksson, 1987; see also section

         The fetal alcohol syndrome is a specific pattern of congenital
    abnormalities found in children of mothers who drink heavily.  The
    abnormalities most typically associated with alcohol-induced
    developmental effects can be grouped into four categories: central
    nervous system dysfunction (mental retardation, microcephaly,
    hyperactivity); growth deficiencies (reduced prenatal length and
    especially weight, with no catch-up postnatal growth; reduced adipose
    tissue, normal growth hormone, cortisol, and gonadotropins); a
    characteristic cluster of facial abnormalities (short palpebral
    fissures, short upturned nose, hypoplastic philtrum, thinned upper-lip
    vermillion, flattened midface); and variable major and minor
    malformations (such as, heart failure, anomalies of the genitalia,
    joints, and palmar creases) (Clarren & Smith, 1978).

         The mechanisms by which ethanol produces its developmental
    effects are not completely understood, and no data are available with
    respect to ethanol doses and/or blood levels needed for such effects. 
    It is generally assumed that acetaldehyde, as the primary metabolite,
    may contribute to the developmental effects of ethanol.  Several
    animal studies have demonstrated the direct teratogenic effect of
    acetaldehyde (Ali & Persaud, 1988; see also section 8.5); however, no
    reports are available with respect to the direct teratogenicity of
    acetaldehyde in humans.


    10.1  Evaluation of human health risks

    10.1.1  Exposure

         By far, the principal source of exposure to acetaldehyde for the
    majority of the general population is through the metabolism of
    alcohol.  Cigarette smoke is also a significant source of exposure for
    smokers.  With respect to other media, the general population is
    exposed to acetaldehyde principally from food, and to a lesser extent
    from air.  Intake from drinking-water is negligible compared with that
    from other media.

         Available data are inadequate to determine the extent of exposure
    to acetaldehyde in the workplace.  Workers may be exposed in some
    manufacturing industries and during alcohol fermentation, where the
    principal route is most likely inhalation and, possibly, dermal

    10.1.2  Health effects

         Acetaldehyde is a reactive molecule that adducts to
    macromolecules and can also condense or polymerise with  small
    molecules.  Although quantitatively unimportant in acetaldehyde
    metabolism, these by-products may have important biological effects.

         In studies conducted on animals, the acute toxicity of
    acetaldehyde by the oral or inhalation routes was low.  Oral LD50s
    ranged from 660 to 1930 mg/kg body weight and LC50s (0.5-4 h) from
    24 to 37 g/m3.  RD50s in rats and mice are slightly greater than
    5000 mg/m3.

         Data on the irritant effects of acetaldehyde on the skin and eye
    are restricted to those from limited studies on human volunteers.  It
    was mildly irritating to the eyes and upper respiratory tract
    following acute exposure for very short periods, in limited studies on
    human volunteers at concentrations exceeding approximately 90 and
    240 mg/m3, respectively (Silverman et al., 1946; Sim & Pattle,
    1957).  Cutaneous erythema was observed in the patch testing of twelve
    subjects of "Oriental ancestry" with acetaldehyde (Wilkin & Fortner,
    1985).  Although a possible mechanism has been identified, available
    data are inadequate to assess the potential of acetaldehyde to induce

         Available data relevant to the assessment of the potential
    adverse effects in humans of exposure to acetaldehyde in the
    occupational and general environments are limited to those on
    irritation mentioned above.  The remainder of this evaluation is,
    therefore, based on studies on animals.

         Effects of acetaldehyde following oral administration to animals
    have been much less well studied than those following inhalation.  In
    one of the two available studies by the oral route, the
    no-observed-effect level (NOEL) following four weeks of administration
    of acetaldehyde to rats was 125 mg/kg body weight per day (Til et al.,
    1988).  At the next higher concentration (675 mg/kg body weight per
    day), a borderline increase in hyperkeratosis of the forestomach was
    observed.  In rats exposed to 0.05% acetaldehyde (estimated by the
    Task Group to be approximately 40 mg/kg body weight) in the
    drinking-water for 6 months, there was an increase in collagen
    synthesis in the liver (Bankowski et al., 1993).  No other effects
    were examined and the toxicological significance of this observation
    is unknown.

         Acetaldehyde has induced gene mutations, clastogenic effects, and
    sister chromatid exchanges (SCE) in mammalian cells  in vitro.
    Though available data on genotoxicity  in vivo are limited, increases
    in SCE have been observed in hamsters and mice exposed
    intraperitoneally to acetaldehyde (Obe et al., 1979; Korte & Obe,
    1981).  This suggests genetic damage to somatic cells  in vivo.
    Available data are inadequate to assess the potential of acetaldehyde
    to induce genetic damage in mammalian germ cells  in vivo.

         On the basis of studies on rats and hamsters, the target tissue
    in inhalation studies is the upper respiratory tract.  In the
    respiratory tract, degenerative changes of the olfactory epithelium in
    rats and trachea in hamsters have been observed at the lowest
    concentrations. Degenerative changes in the respiratory epithelium and
    larynx have been observed at higher concentrations.  In available
    studies, the lowest concentration at which effects were observed
    (degenerative changes in the olfactory epithelium of rats) was
    437 mg/m3 following administration for 5 weeks (Saldiva et al.,
    1985). The NOELs identified for respiratory effects were 275 mg/m3
    in rats exposed for 4 weeks (Appelman et al., 1986) and 700 mg/m3 in
    hamsters exposed for 13 weeks (Kruysse et al., 1975).

         Increased incidences of tumours have been observed in inhalation
    studies on rats and hamsters exposed to acetaldehyde.  In rats, there
    were dose-related increases in nasal adenocarcinomas and squamous cell
    carcinomas (significant at all doses of 1350 mg/m3 and greater)
    (Woutersen et al., 1986) and non significant increases in laryngeal
    and nasal carcinomas in hamsters (Feron et al., 1982).  All
    concentrations of acetaldehyde administered in these studies induced
    tissue damage in the respiratory tract.  On the basis of limited
    available data, no conclusions can be drawn concerning the potential
    of acetaldehyde to promote tumours.

         The distribution of nasal lesions induced in rats exposed to
    acetaldehyde in inhalation studies correlates with regional
    deficiencies in ALDH, observed in a different strain of rats,
    prompting the authors to suggest that regional susceptibility to the
    toxic effects may be due, at least in part, to a lack of ALDH in the
    susceptible regions (Bogdanffy et al., 1986).

         Available data are inadequate for assessment of the potential
    reproductive, developmental, neurological, or immunological effects
    associated with exposure to acetaldehyde in occupationally exposed or
    general populations.

    10.1.3  Approaches to risk assessment

         The following guidance is provided as a potential basis for
    derivation of limits of exposure by relevant authorities.  Though the
    principal sources of exposure to acetaldehyde in the general
    population are through the metabolism of alcohol, in cigarette smoke,
    and food, air is believed to be the main route of exposure in the
    occupational environment.  In addition, available data are inadequate
    to provide guidance concerning the potential risks associated with
    oral exposure to acetaldehyde.  On this basis, only air is addressed

         On the basis of data on irritancy in humans, a tolerable
    concentration can be derived as follows:

                                45 mg/m3
    Tolerable concentration =               = 2 mg/m3 (2000 µg/m3)


    no effects were observed in a limited study on human volunteers at
    45 mg/m3 (Silverman et al., 1946) and 20 is the uncertainty factor
    (×10 for intraspecies variation and × 2 for the poor quality of the

         Data suggest that acetaldehyde causes genetic damage to
    somatic cells  in vivo.  The irritancy of acetaldehyde may also play
    an important role in the development of tumours in the nose and larynx
    of rats and hamsters, respectively, exposed by inhalation, though all
    concentrations of acetaldehyde administered in carcinogenesis
    bioassays induced both irritancy and nasal tumours.  Therefore, two
    approaches were adopted for the provision of guidance with respect to
    the potential carcinogenicity of acetaldehyde.

         In the first, a tolerable concentration (TC) was derived on the
    basis of division of an effect level for irritancy in the respiratory
    tract of rodents by an uncertainty factor, based on the principles
    outlined in WHO (in press) and the assumption that there is a
    threshold for acetaldehyde-induced cancer of the respiratory tract in
    rodents exposed via inhalation.  There is some support for this
    approach on the basis of relevant data on the analogues of
    acetaldehyde, i.e., formaldehyde and glutaraldehyde, which have
    similar spectra of  in vitro mutagenic effects, but are clearly not
    mutagenic  in vivo (IARC, 1985; WHO, 1989).  Thus,

                                275 mg/m3
    Tolerable concentration =                = 0.3 mg/m3 (300 µg/m3)


    275 mg/m3 was the NOEL for irritation in rats in a 4-week study
    (Appelman et al., 1986) and 1000 is the uncertainty factor (×10 for
    interspecies variation, ×10 for intraspecies variation and ×10 for a
    less than long-term study and severity of effect, i.e.,
    carcinogenicity associated with irritation).

         Since the mechanism of induction of tumours by acetaldehyde has
    not been well studied, lifetime cancer risk has also been estimated on
    the basis of a default model (i.e., linearized multistage) (WHO, in
    press).  However, it is very likely that, since estimated risk is
    based on tumour incidence at concentrations that induce irritancy in
    the respiratory tract and no-observed-effect levels for irritancy are
    well below these concentrations, the true cancer risk is most likely
    much lower at concentrations generally present in the environment and
    may, indeed, be zero.

         Concentrations associated with a 10-5 excess lifetime risk (lower
    95% confidence limits) for nasal tumours (adenocarcinomas, squamous
    cell carcinomas, and carcinomas  in situ) in male and female rats, in
    the only carcinogenicity study in which animals were exposed via
    inhalation to acetaldehyde over the lifetime (Woutersen et al., 1986),
    calculated on the basis of the linearized multistage model (Global
    82), are 11-65 µg/m3.  The high-dose animal groups were excluded in
    the derivation of these estimates because of early mortality.  A body
    surface area correction was not incorporated.

    10.2  Evaluation of effects on the environment

         Acetaldehyde enters the environment during industrial production,
    as a product of incomplete combustion (e.g., in vehicle exhausts) and
    as a product of alcohol fermentation.  Once released,
    intercompartmental transport of acetaldehyde is expected to be
    limited, because of its reactivity.  However, because of its high
    vapour pressure and low tendency for sorption onto soil, it is most
    likely to be present in air.  Acetaldehyde is readily biodegradable;
    approximate half-lives are 10-60 h and 1.9 h in air and water,

         No quantitative data on levels in ambient water were identified. 
    However, on the basis of concentrations measured in drinking-water,
    levels in the aquatic environment are expected to be low (i.e., less
    than 0.1 µg/litre).  Concentrations in ambient air average about
    5 µg/m3.

         Acetaldehyde is slightly toxic for fish.  The lowest reported
    LC50 was 35 µg/litre  (Poecilia reticulata).  No long-term toxicity
    tests have been performed.  Acetaldehyde is toxic for micro-organisms
    at relatively low concentrations.  Seed germination of several plants
    was inhibited by more than 50% after exposure to 1.52 mg/litre (3 h). 
    There were no effects on lettuce exposed to 0.36 µg/m3 acetaldehyde.

         The limited available data preclude definitive conclusions
    concerning the potential risks of acetaldehyde for environmental
    biota.  However, on the basis of the short half-lives of acetaldehyde
    in air and water and the fact that it is readily biodegradable, the
    impact of acetaldehyde on organisms in the aquatic and terrestrial
    environments is expected to be low, except, possibly, during
    industrial discharges or spills.


    1.   Additional studies on the fate in the environment and impact of
         acetaldehyde on biota.

    2.   Additional information on exposure of workers in the occupational
         environment and levels in the vicinity of industrial facilities.

    3.   Carcinogenesis bioassays by the inhalation route including doses
         that do not induce cytotoxicity (e.g., 275  mg/m3).

    4.   Studies on the biological significance of byproducts of
         acetaldehyde, such as acetaldehyde-modified proteins.

    5.   Studies on pathogenicity, reproductive and developmental
         toxicity, and genotoxicity  in vivo by relevant routes of

    6.   Additional studies on toxicity following ingestion in
         experimental animals.

    7.   Studies of irritation in workers exposed to acetaldehyde.


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    1.  Identité, propriétés physiques et chimiques et méthodes d'analyse

         L'acétaldéhyde est un liquide incolore et volatil à l'odeur acre
    et suffocante.  D'après la littérature, son seuil olfactif est de
    0,09 mg/m3.  L'acétaldéhyde est un composé très inflammable et
    réactif qui est miscible à l'eau et à la plupart des solvants

         Il existe un certain nombre de méthodes d'analyse pour la
    recherche de l'acétaldéhyde dans l'air (y compris dans l'haleine) et
    dans l'eau.  La principale méthode repose sur la réaction de
    l'acétaldéhyde avec la 2,4-dinitrophénylhydrazine, puis analyse de
    l'hydrazone obtenue par chromatographie liquide à haute pression ou
    chromatographie en phase gazeuse.

    2.  Sources d'exposition humaine et environnementale

         L'acétaldéhyde est un intermédiaire métabolique chez l'homme et
    les plantes supérieures; c'est également un produit de la fermentation
    alcoolique.  On a décelé sa présence dans certaines denrées
    alimentaires et boissons ainsi que dans la fumée de cigarette.  Il est
    également présent dans les gaz d'échappement des véhicules à moteur
    ainsi que dans divers déchets industriels.  La décomposition des
    hydrocarbures, des effluents d'égouts et des déchets biologiques
    solides produit de l'acétaldéhyde, de même que la combustion à l'air
    libre ou, selon le cas, l'incinération du gaz, du mazout et de la

         Plus de 80% de l'acétaldéhyde utilisé à des fins commerciales est
    produit par l'oxydation en phase liquide de l'éthylène en présence
    d'une solution catalytique de chlorures de palladium et de cuivre.  Au
    Japon, la production était de 323.000 tonnes en 1981.  Aux Etats-Unis
    d'Amérique elle a été de 281.000 tonnes en 1982 et en Europe
    occidentale de 706.000 tonnes en 1983.  La majeure partie de
    l'acétaldéhyde produit commercialement est utilisé pour la préparation
    de l'acide acétique.  On l'utilise également pour la préparation de
    certains arômes et denrées alimentaires.

         On estime qu'aux Etats-Unis d'Amérique, les émissions annuelles
    d'acétaldéhyde de toutes origines atteignent 12,2 millions de kg.

    3.  Transport, distribution et transformation dans l'environnement

         En raison de la forte réactivité de l'acétaldéhyde, le transport
    intercompartimental de ce composé devrait être limité.  On peut
    s'attendre à un certain transfert d'acétaldéhyde de l'air vers l'eau
    et le sol en raison de sa forte tension de vapeur et de son faible
    coefficient de sorption.

         On pense que l'élimination photo-induite de l'acétaldéhyde
    atmosphérique passe essentiellement par la formation de radicaux.  La
    photolyse devrait jouer également un rôle important dans le processus
    d'élimination. Environ 80% des émissions d'acétaldéhyde dans
    l'atmosphère sont éliminés chaque jour par ces deux processus. 
    D'après la littérature, la demi-vie de l'acétaldéhyde dans l'eau et
    l'air est respectivement égale à 1,9 heure et 10-60 heures.

         L'acétaldéhyde est facilement biodégradable.

    4.  Concentrations dans l'environnement et exposition humaine

         Les concentrations moyennes d'acétaldéhyde dans l'environnement
    sont généralement égales à 5 µg/m3.  Dans l'eau, elles sont
    généralement inférieures à 0,1 µg/litre.  L'analyse de denrées
    alimentaires très diverses effectuées aux Pays-Bas a montré que leur
    teneur en acétaldéhyde est généralement inférieure à 1 mg/kg, mais
    peut atteindre occasionnellement jusqu'à plusieurs centaines de mg/kg,
    en particulier dans certains jus de fruit et dans le vinaigre.

         Pour la population générale, la principale source d'exposition à
    l'acétaldéhyde est de loin le métabolisme de l'alcool.  La fumée de
    cigarette constitue également une importante source d'exposition.  En
    ce qui concerne les autres véhicules, la population générale est
    exposée à l'acétaldéhyde essentiellement par l'intermédiaire de la
    nourriture et des boissons et, dans une moindre mesure, de l'air. 
    L'eau de boisson est négligeable à cet égard.

         Les données disponibles sont insuffisantes pour qu'on puisse
    évaluer l'ampleur de l'exposition à l'acétaldéhyde sur les lieux de
    travail.  Les travailleurs peuvent y être exposés dans certaines
    industries ainsi que lors de la fermentation de l'alcool; dans ces
    conditions la principale voie d'exposition est très probablement
    l'inhalation avec possibilité également de contacts cutanés.

    5.  Cinétique et métabolisme

    5.1  Absorption, distribution et élimination

         Les données toxicologiques dont on dispose indiquent que
    l'acétaldéhyde est résorbé au niveau des poumons et des voies
    digestives; toutefois on ne connaît pas d'études quantitatives
    appropriées qui aient été consacrées à ce problème.  Il est probable
    qu'il y a également une résorption cutanée.

         Après avoir fait inhaler de l'acétaldéhyde à des rats, on a
    constaté qu'il se répartissait dans le sang, le foie, les reins, la
    rate, le coeur et le tissu musculaire.  De faibles quantités en ont
    été décelées dans des embryons après injection intrapéritonéale à la
    mère (souris) ainsi qu'après exposition de la mère à de l'éthanol
    (souris et rat). Il pourrait également y avoir production
    d'acétaldé-hyde  in vitro chez les foetus de rat et dans le placenta

         Après injection intrapéritonéale d'éthanol, on a pu mettre en
    évidence la distribution de l'acétaldéhyde dans le liquide
    interstitiel de l'encéphale, à l'exclusion des cellules cérébrales. Il
    est possible qu'une acétaldéhyde-déshydrogénase de forte affinité et
    de faible Km joue un rôle important dans le maintien de faibles
    concentrations d'acétaldéhyde dans le cerveau au cours de la
    métabolisation de l'éthanol.

         On a constaté que chez l'homme et les babouins, l'acétaldéhyde
    pouvait être fixé par les globules rouges  in vivo, la concentration
    intraglobulaire pouvant atteindre dix fois la concentration

         Après administration par voie orale, il n'y a pratiquement pas
    d'acétaldéhyde qui soit excrété tel quel dans les urines.

    5.2  Métabolisme

         La principale voie métabolique de l'acétaldéhyde consiste dans
    une oxydation en acétate sous l'action de l'ALDHa NADb-dépendante.
    L'acétate entre dans le cycle de l'acide citrique sous forme
    d'acétyl-CoA.  Il existe plusieurs isoenzymes de l'ALDH présentant
    divers paramètres cinétiques et paramètres de liaison qui influent sur
    la vitesse d'oxydation de l'acétaldéhyde.

         Chez le rat, on a pu localiser une activité ALDH dans
    l'épithélium respiratoire (à l'exclusion de l'épithélium olfactif),
    alors que cette localisation se situe au niveau du rein chez la souris
    et au niveau du cortex et des tubules rénaux chez le chien, le rat, le
    cobaye et le babouin.

         Les tissus embryonnaires de souris et de rat métabolisent
    l'acétaldéhyde  in vitro.  L'acétaldéhyde traverse le placenta du rat
    malgré l'existence d'un métabolisme placentaire.


    a  acétaldéhyde-déshydrogénase

    b  nicotinamide-adénine-dinucléotide

         Il y a un certaine métabolisation de l'acétaldéhyde au niveau des
    tubules rénaux chez l'homme mais c'est le foie qui est le principal
    site du métabolisme.

         Chez l'homme, on a décelé la présence de plusieurs formes
    isoenzymatiques d'ALDH, au niveau du foie et d'autres tissus.  Il y a
    également un polymorphisme de l'ALDH michocondrial.  Les sujets qui
    sont homozygotes ou hétérozygotes pour une mutation ponctuelle du gène
    correspondant à l'ALDH mitrochondriale, présentent une faible activité
    ALDH, métabolisent lentement l'acétaldéhyde et ne supportent pas
    l'alcool éthylique.

         Le crotonadéhyde, la maléate de diméthyle, la phorone, le
    disulfirame et le carbamide calcique inhibent le métabolisme de

    5.3  Réactions avec d'autres constituants

         L'acétaldéhyde forme des adduits stables ou instables avec les
    protéines.  Ces adduits peuvent perturber la fonction de ces protéines
    comme le montre d'ailleurs l'inhibition des enzymes, les difficultés
    de liaison entre histones et ADN et l'inhibition de la polymérisation
    de la tubuline.

         Des adduits instables de l'acétaldéhyde dont on connaît mal
    l'importance se forment  in vitro avec les acides nucléiques.

         L'acétaldéhyde peut réagir sur diverses macromolécules de
    l'organisme, de préférence avec celles qui sont porteuses de résidus
    de lysine; cette réaction peut conduire à des altérations importantes
    de la fonction biologique de ces molécules.

    6.  Effets sur les êtres vivants dans leur milieu naturel

    6.1  Organismes aquatiques

         Chez les poissons la CL50 peut varier de 35 mg/litre (guppy) à
    140 mg/litre (espèces non précisées).  Une CE5 de 82 mg/litre et une
    CE50 de 42 mg/litre ont été observées respectivement chez des algues
    et chez  Daphnia magna.

    6.2  Organismes terrestres

         La présence d'acétaldéhyde dans l'air se révèle toxique pour
    certains microorganismes, à des concentrations relativement faibles.

         Des aphidiens ont été tués par exposition de 3 à 4 heures à de
    l'acétaldéhyde à une concentration de 0,36 µg/m3.

         Chez deux espèces de limaces,  Arion hortensis et  Agriolimax
    reticulatus, on a observé des concentrations létales médianes
    respectivement égales à 8,91 mg/litre et par heure et 7,69 mg/litre et
    par heure.

         L'acétaldéhyde provoque une inhibition réversible de la
    germination des oignons, des carottes et des tomates à des
    concentrations allant jusqu'à 1,52 mg/litre; par contre cette
    inhibition est irréversible pour  Amaranthus palmeri, dans les mêmes
    conditions d'exposition.  A la concentration de 0.54 µg/m3,
    l'acétaldéhyde a détérioré des laitues.

    7.  Effets sur les animaux de laboratoire et les systèmes d'épreuve
        in vitro

    7.1  Exposition unique

         Les valeurs de la DL50 pour le rat et la souris et de la CL50
    pour le rat et le hamster doré montrent que la toxicité aiguë de
    l'acétaldéhyde est faible.  On n'a pas connaissance d'études relatives
    à la toxicité cutanée aiguë de l'acétaldéhyde.

    7.2  Exposition à court et à long terme

         Lors d'études au cours desquelles des doses ont été administrées
    à plusieurs reprises, tant par la voie orale que par la voie
    respiratoire, les effets toxiques observés à des concentrations
    relativement faibles se limitaient essentiellement aux points de
    contact initiaux.  Lors d'une étude de 28 jours au cours de laquelle
    de l'acétaldéhyde a été administré à des rats, mélangé à leur eau de
    boisson, à la dose de 675 mg/kg de poids corporel (dose sans effets
    observables 125 mg/kg de poids corporel), on a constaté que les effets
    se limitaient à une légère hyperkératose focale au niveau de la
    portion cardiaque de l'estomac.  Après administration d'acétaldéhyde à
    concentration constante de 0,05% dans l'eau de boisson pendant une
    durée de 6 mois (le Groupe de travail estime que cela correspond à peu
    près à 40 mg/kg de poids corporel) au cours d'une étude biochimique,
    on a constaté que l'acétaldéhyde provoquait la synthèse de collagène
    au niveau du foie chez le rat, observation d'ailleurs corroborée par
    les résultats obtenus  in vitro.

         Lors d'une étude d'inhalation de 4 semaines chez le rat et de 13
    semaines chez le hamster, on a obtenu, pour la concentration sans
    effets respiratoires observables, des valeurs respectivement égales à
    275 mg/m3 et 700 mg/m3.  Aux concentrations les plus faibles
    produisant un effet, on a observé des altérations dégénératives au
    niveau de l'épithélium olfactif chez le rat (437 mg/m3) et de la
    trachée (2400 mg/m3) chez le hamster.  Des altérations dégénératives
    de l'épithélium respiratoire et du larynx ont été observées à des
    concentrations plus élevées.  On n'a pas connaissance d'études
    relatives à l'administration répétée d'acétaldéhyde au niveau cutané.

    7.3  Reproduction, embryotoxicité et tératogénicité

         Plusieurs études montrent que des malformations foetales peuvent
    survenir par suite de l'exposition parentérale de rattes et de souris
    gravides à l'acétaldéhyde.  Dans la plupart de ces études, on n'a pas
    étudié la toxicité pour la mère.  On n'a pas pu trouver de données
    relatives à la toxicité de l'acétaldéhyde pour la fonction de

    7.4  Mutagénicité et points d'aboutissement des effets correspondants

          In vitro, l'acétaldéhyde est génotoxique et produit des
    mutations géniques, des effets clastogènes ainsi que des échanges
    entre chromatides soeurs dans des cultures de cellules mammaliennes en
    l'absence d'activation métabolique exogène.  Toutefois, des épreuves
    effectuées dans les règles sur des salmonelles ont donné des résultats
    négatifs.  Après avoir injecté de l'acétaldéhyde par voie
    intrapéritonéale à des hamsters chinois et à des souris, on a constaté
    que ce composé produisait des échanges entre chromatides soeurs au
    niveau de la moelle osseuse.  Cependant, de l'acétaldéhyde administré
    par la même voie n'a pas eu pour conséquence un accroissement de la
    fréquence des micronoyaux dans les spermatides de souris récemment
    formés.  On peut déduire indirectement de certaines études  in vitro
    et  in vivo que l'acétaldéhyde est susceptible de produire des
    pontages protéines-ADN et ADN-ADN.

    7.5  Cancérogénicité

         Des études d'inhalation effectuées sur des rats et des hamsters
    ont permis de constater un accroissement de l'incidence des tumeurs. 
    Chez le rat, il s'agissait d'une augmentation, liée à la dose, de la
    fréquence des adénocarcinomes au niveau de la muqueuse nasale ainsi
    que des carcinomes spino-cellulaires (accroissement significatif à
    toutes les doses). Toutefois chez le hamster, l'accroissement constaté
    de la fréquence des carcinomes du nez et du larynx n'était pas
    significatif.  A toutes les concentrations d'acétaldéhyde, on a
    constaté l'apparition de lésions tissulaires chroniques au niveau des
    voies respiratoires.

    7.6  Etudes spéciales

         On n'a pas connaissance d'études appropriées portant sur la
    neuro- et l'immunotoxicité potentielle de l'acétaldéhyde.

    8.  Effets sur l'homme

         Lors d'études limitées portant sur des volontaires humains, on a
    constaté que l'acétaldéhyde avait un effet légèrement irritant sur les
    yeux et les voies respiratoires supérieures, après exposition de très
    brève durée à des concentrations respectivement supérieures à environ
    90 et 240 mg/m3.  Après l'application d'un timbre inbibé
    d'acétaldéhyde, on a constaté la présence d'un érythème cutané chez 12
    sujets "d'ascendance orientale".

         On a signalé l'existence d'une enquête limitée au cours de
    laquelle on a étudié l'incidence des cancers chez des travailleurs
    exposés à de l'acétaldéhyde.

         On possède des preuves indirectes que le métabolite toxique
    supposé être à l'origine des lésions hépatiques imputables à l'alcool,
    de bouffées de chaleur et d'effets sur la développement, est en fait

    9.  Evaluation des risques pour la santé humaine et des effets
        sur l'environnement

         Les études effectuées sur l'animal montrent que, par voie
    respiratoire ou par voie orale, l'acétaldéhyde n'est que faiblement
    toxique.  D'après les études effectuées sur l'animal mais également
    sur l'homme, on a constaté que ce composé était légèrement irritant
    pour l'oeil et les voies respiratoires supérieures.  Chez l'homme,
    l'application d'un timbre cutané inbibé d'acétaldéhyde peut provoquer
    l'apparition d'un érythème cutané.  On pense avoir découvert le
    mécanisme à l'origine de cet effet mais les données disponibles sont
    encore insuffisantes pour qu'on puisse évaluer le pouvoir
    sensibilisateur de l'acétaldéhyde.

         On ne dispose que de données limitées sur les effets d'une
    ingestion d'acétaldéhyde.  Après administration d'acétaldéhyde par
    voie orale à des rats à la dose quotidienne de 675 mg/kg de poids
    corporel, on a constaté un accroissement limite de l'hyperkératose au
    niveau de la portion cardiaque de l'estomac (dose sans effets nocifs
    observables:  125 mg/kg de poids corporel).  Après avoir fait boire à
    des rats six mois durant de l'eau contenant environ 40 mg
    d'acétaldéhyde/kg de poids corporel, on a constaté un accroissement de
    la synthèse du collagène hépatique, effet dont la signification reste

         D'après des études effectuées sur des rats et des hamsters, ce
    sont les voies respiratoires supérieures qui constituent l'organe
    cible de l'acétaldéhyde lorsque ce composé est inhalé.  D'après les
    résultats obtenus, la concentration la plus faible à laquelle on a

    commencé à observer des effets était de 437 mg/m3, après une période
    d'administration de 5 semaines.  Chez des rats exposés pendant 4
    semaines, la dose sans effets respiratoires observables était de
    275 mg/m3; elle était de 700 mg/m3 chez des hamsters exposés
    pendant 13 semaines.

         Aux concentrations qui produisaient des lésions tissulaires des
    voies respiratoires, on a observé un accroissement de l'incidence des
    adénocarcinomes du nez et des carcinomes spino-cellulaires chez le
    rat; il y a également eu accroissement des carcinomes du larynx et du
    nez chez le hamster.

         On est fondé à penser qu' in vivo, l'acétaldéhyde provoque des
    lésions génétiques dans les cellules somatiques.

         les données disponibles sont insuffisantes pour qu'on puisse
    apprécier les effets qu'une exposition à l'acétaldéhyde pourrait avoir
    sur la reproduction, le développement ainsi que les fonctions
    neurologiques et immunologiques de la population générale ou de la
    population professionnellement exposées.

         Pour ce qui est du pouvoir irritant de ce composé chez l'homme,
    on estime que la concentration tolérable est de 2 mg/m3.  Etant
    donné que le mécanisme d'induction de tumeurs par l'acétaldéhyde n'a
    pas été bien étudié, on a adopté deux approches concernant ce point
    d'aboutissement de son action toxique, à savoir la fixation d'une
    concentration tolérable qui serait obtenue en divisant la dose
    irritante pour les voies respiratoires chez les rongeurs, par un
    certain facteur d'incertitude et l'estimation d'un risque de cancer
    sur toute la durée de l'existence, en procédant par extrapolation
    linéaire.  La concentration tolérable est de 0,3 mg/m3.  La
    concentration produisant un excès de risque de 10-5 sur toute la durée
    de la vie se situe entre 11-65 µg/m3.

         Les données limitées dont on dispose ne permettent pas de tirer
    des conclusions définitives quant au risque que l'acétaldéhyde
    pourrait représenter pour l'ensemble de la faune et de la flore. 
    Toutefois, si l'on considère la courte durée de vie de l'acétaldéhyde
    dans l'air et dans l'eau et le fait qu'il est facilement
    biodégradable, on est amené à penser que ce composé n'est guère
    menaçant pour les organismes aquatiques ou terrestres, sauf peut-être
    en cas de décharge ou de déversement de produits industriels.


    1.  Identidad, propiedades físicas y químicas y métodos analíticos

         El acetaldehído es un líquido incoloro, volátil y de olor acre y
    sofocante.  El umbral señalado para el olor es de 0,09 mg/m3.  El
    acetaldehído es un compuesto muy inflamable y reactivo, soluble en
    agua y en la mayoría de los disolventes comunes.

         Existen métodos de análisis para la detección del acetaldehído en
    el aire (incluso en el aliento) y en el agua.  El principal de ellos
    se basa en la reacción del producto con 2,4-dinitrofenilhidracina y
    ulterior análisis de los derivados de la hidrazona por cromatografía
    de líquidos a alta presión o cromatografía de gases.

    2.  Fuentes de exposición humana y ambiental

         El acetaldehído es un producto intermedio del metabolismo en los
    hombres y en las plantas superiores, y también proviene de la
    fermentación alcohólica.  Ha sido identificado en los alimentos, las
    bebidas y el humo de los cigarrillos.  También se encuentra en los
    gases de escape de los vehículos y en ciertos desechos industriales. 
    La degradación de los hidrocarburos, las aguas residuales y los
    desechos biológicos sólidos produce acetaldehído, como también lo
    hacen la combustión al aire libre y la incineración de gas, fuel oil y

         Más del 80% del acetaldehído usado comercialmente proviene de la
    oxidación en fase líquida de etileno con una solución catalítica de
    paladio y cloruros de cobre.  En 1981, la producción japonesa fue de
    323 000 toneladas.  En los Estados Unidos de América fue de 281 000
    toneladas en 1982 y en Europa occidental de 706 000 toneladas en 1983. 
    La mayoría del acetaldehído producido comercialmente se destina a la
    fabricación de ácido acético.  También se utiliza en sustancias
    aromáticas y en alimentos.

         En los Estados Unidos, la emisión anual de acetaldehído de todo
    origen se calcula en 12,2 millones de kilogramos.

    3.  Transporte, distribución y transformación en el medio ambiente

         Debido a su alta reactividad, el transporte intercompartimental
    de acetaldehído debe ser limitado.  Es de suponer que hay cierta
    transferencia de la sustancia al aire desde el agua y el suelo, como
    consecuencia de la fuerte presión del vapor y el bajo coeficiente de

         Es posible que la eliminación fotoinducida del acetaldehído en la
    atmósfera tenga lugar principalmente por formación de un radical.  La
    fotosíntesis puede también contribuir bastante al proceso de
    eliminación.  La pérdida resultante de acetaldehído proveniente de
    emisiones en la atmósfera es de alrededor del 80%.  La vida media de
    la sustancia en el agua y en el aire es de 1,9 h y 10-60 h,

         El acetaldehído es muy biodegradable.

    4.  Niveles medioambientales y exposición humana

         Los niveles de acetaldehído en el aire ambiente suelen ser por
    término medio de 5 µg/m3.  Las concentraciones en el agua no llegan
    en general a 0,1 µg/litro.  El análisis de diversos alimentos en los
    Países Bajos demostró que las concentraciones, normalmente inferiores
    a 1 mg/kg, a veces llegaban a 100 mg/kg, particularmente en algunos
    zumos de frutas y en el vinagre.

         La principal fuente, con mucho, de exposición al acetaldehído
    para la mayoría de la población es el metabolismo del alcohol.  El
    humo del cigarrillo es también una fuente significativa.  Aparte de
    eso pueden mencionarse en segundo lugar los alimentos y bebidas y, en
    menor grado, el aire.  La contribución del agua de beber es

         No existen datos suficientes para determinar la importancia de la
    exposición al acetaldehído en el lugar de trabajo.  El personal puede
    estar expuesto en algunas industrias manufactureras y donde hay
    fermentación con producción de alcohol, siendo la principal vía la
    inhalación y posiblemente el contacto con la piel.

    5.  Cinética y metabolismo

    5.1  Absorción, distribución y eliminación

         Los estudios existentes sobre toxicidad indican que el
    acetaldehído se absorbe por los pulmones y el conducto
    gastrointestinal; sin embargo, no parecen existir análisis
    cuantitativos adecuados.  Es probable la absorción por la piel.

         En las ratas, el acetaldehído inhalado se distribuye por la
    sangre, pasando al hígado, el riñón, el bazo, el corazón y otros
    tejidos musculares.  Se han detectado bajos niveles en embriones de
    ratón tras inyectar la sustancia a la madre por vía intraperitoneal o
    tras exposición de ratas o ratones hembra a etanol.  La producción
    potencial de acetaldehído  in vitro se ha observado en fetos de rata
    y en la placenta humana.

         Tras inyección intraperitoneal de etanol se ha demostrado la
    distribución de acetaldehído en el líquido intersticial pero no en las
    células del cerebro.  Una alta afinidad y escaso Km ALDHa pueden ser
    importantes para mantener bajos niveles de acetaldehído en el cerebro
    durante el metabolismo del etanol.

         El acetaldehído es absorbido por los eritrocitos y, tras consumo
    de etanol, los niveles intracelulares en hombres y babuinos pueden ser
     in vivo 10 veces más altos que los del plasma.

         Después de la administración por vía oral, la excreción de
    acetaldehído por la orina prácticamente no cambia.

    5.2  Metabolismo

         Un medio importante en el metabolismo del acetaldehído es la
    oxidación para pasar a acetato bajo la influencia de una ALDH
    dependiente de NADb.  El acetato pasa al ciclo de ácido cítrico como
    acetil-CoA.  Hay varios isoenzimas de ALDH con distintos parámetros
    cinéticos y de ligazón que influyen en la rapidez de la oxidación del

         Se ha detectado actividad de la ALDH en el epitelio del tracto
    respiratorio (excluido el de las vías olfativas) de ratas, en el
    cortex renal y los túbulos del perro, la rata, el cobayo y el babuino,
    y también en los testículos del ratón.

         El acetaldehído es metabolizado  in vitro por el tejido
    embrionario del ratón y la rata.  La sustancia atraviesa la placenta
    del ratón, pese al metabolismo placentario.

         Aunque hay algún metabolismo en los túbulos renales humanos, el
    principal órgano metabolizador es el hígado.

         En el hígado y otros tejidos humanos se han detectado varias
    formas isoenzimáticas de ALDH.  En las mitocondrias la ALDH presenta
    polimorfismo.  Los sujetos que son homozigóticos o heterozigóticos por
    una mutación singular del gen correspondiente a la ALDH de las
    mitocondrias presentan poca actividad de esta enzima, metabolizan el
    acetaldehído lentamente y no toleran el etanol.

         El metabolismo del acetaldehído puede ser inhibido por el
    crotonaldehído, el dimetilmaleato, el forón, el disulfiram y la
    carbamida de calcio.

    5.3  Reacción con otros compuestos

         El acetaldehído puede formar aductores estables e inestables con
    las proteínas.  Eso menoscaba la función proteínica, como lo demuestra
    la inhibición de la actividad enzimática, la menor ligazón histona-ADN
    y la polimerización inhibida de la tubulina.

         Los aductores inestables, de importancia indeterminada, se
    producen  in vitro con ácidos nucleicos.

         El acetaldehído puede reaccionar con diversas macromoléculas en
    el organismo humano, de preferencia las que contienen residuos de
    lisina, lo que puede conducir a notables alteraciones de la función
    biológica de dichas moléculas.

    6.  Efectos sobre los organismos presentes en el medioambiente

    6.1  Organismos acuáticos

         La CL50 para los peces va de 35  (Lebistes reticulatus) a
    140 mg/litro (especies no especificadas).  Se ha señalado una CE5 de
    82 mg/litro y una CE50 de 42 mg/litro para las algas y para  Daphnia
     magna, respectivamente.

    6.2  Organismos terrestres

         El acetaldehído atmosférico a concentraciones relativamente bajas
    parece ser tóxico para algunos microorganismos.

         Los afidios mueren cuando son expuestos a concentraciones de
    0,36 µg/m3 durante tres o cuatro horas.

         Para las especies de babosa  Arion hortensis y  Agriolimax
     reticulatus se han registrado valores letales medios de
    8,91 mg/litro y 7,69 mg/litro por hora, respectivamente.

         La inhibición de la germinación para la semilla de cebolla,
    zanahoria y tomate tratada con acetaldehído (hasta 1,52 mg/litro) es
    reversible, mientras que la de  Amaranthus palmeri expuesta del mismo
    modo es irreversible.  El acetaldehído a 0,54 µg/m3 es perjudicial
    para la lechuga.

    7.  Efectos en animales experimentales y sistemas de prueba in vitro

    7.1  Exposición única

         El acetaldehído tiene una toxicidad aguda baja, con una DL50 en
    ratas y ratones y una CL50 en ratas y hámsters sirios.  No se han
    encontrado estudios de toxicidad dérmica aguda.

    7.2  Exposición a corto y a largo plazo

         En estudios reiterados del efecto tóxico de dosis por vía oral y
    por inhalación, los efectos tóxicos de concentraciones relativamente
    bajas se limitaron más bien a los puntos de contacto inicial. En un
    estudio de 28 días en el que se administró a ratas con el agua de
    beber acetaldehído a razón de 675 mg/kg de peso corporal (nivel sin

    efecto observado (NOEL) = 125 mg/kg de peso corporal) los efectos se
    limitaron a una ligera hiperqueratosis focal en la parte anterior del
    estómago.  En un estudio bioquímico, tras la administración a ratas de
    dosis singulares (0,05% en el agua de beber) durante seis meses
    (equivalente según el Grupo Especial a alrededor de un 40 mg/kg de
    peso corporal), el acetaldehído indujo la síntesis de colágeno
    hepático, observación corroborada mediante pruebas  in vitro.

         El nivel sin efecto respiratorio observado (NOEL) fue de
    275 mg/m3 para ratas expuestas a acetaldehído por inhalación durante
    cuatro semanas y 700 mg/m3 en hámsters expuestos durante 13 semanas.
    A los niveles más bajos de efecto observado se produjeron cambios
    degenerativos del epitelio olfativo en ratas (437 mg/m3) y de la
    tráquea (2400 mg/m3) en hámsters.  A concentraciones superiores se
    produjeron cambios degenerativos del epitelio respiratorio y de la
    laringe.  No se han identificado estudios dérmicos con dosis

    7.3  Reproducción, embriotoxicidad y teratogenicidad

         En varios estudios, la exposición parenteral de ratas y ratones
    gestantes a acetaldehído produjo malformaciones fetales.  En la
    mayoría de esos estudios no se evaluó la toxicidad materna.  Tampoco
    se dispone de datos sobre la toxicidad reproductiva.

    7.4  Mutagenicidad y otros efectos finales afines

         El acetaldehído es genotóxico  in vitro e induce mutación de los
    genes, con efectos clastogénicos e intercambios de cromatidios
    hermanos (SCE) en las células de mamíferos, en ausencia de activación
    metabólica exógena.  Sin embargo se han registrado resultados
    negativos en pruebas adecuadas con Salmonella.  Tras inyección
    intraperitoneal, el acetaldehído indujo SCE en la médula ósea de
    hámsters chinos y ratones pero, en cambio, no hizo aumentar la
    frecuencia de los micronúcleos en las espermátides precoces de ratón. 
    Indirectamente, ciertos estudios  in vitro e  in vivo parecen
    indicar que el acetaldehído puede inducir enlaces cruzados
    proteína-ADN y ADN-ADN.

    7.5  Carcinogenicidad

         Se ha observado una mayor incidencia de tumores en ratas y
    hámsters expuestos a acetaldehído por inhalación.  En las ratas, los
    adenocarcinomas nasales aumentaron según la dosis pero los carcinomas
    de células escamosas fueron significativos independientemente de la
    dosis.  Por el contrario, en los hámsters, el aumento de los
    carcinomas nasales y laríngeos fue insignificante.  A todas las
    concentraciones, el acetaldehído administrado en los estudios produjo
    daños irreversibles del tejido respiratorio.

    7.6  Estudios especiales

         No se conocen estudios adecuados sobre la neurotoxicidad y la
    inmunotoxicidad potencial del acetaldehído.

    8.  Efectos en el ser humano

         En estudios limitados con voluntarios, el acetaldehído produjo
    irritación moderada de los ojos y de las vías respiratorias superiores
    tras exposición por muy breves periodos a concentraciones que excedían
    algo de 90 y 240 mg/m3, respectivamente.  Las pruebas de parche
    efectuadas con acetaldehído produjeron eritema cutáneo en 12 sujetos
    de «ascendencia oriental».

         Se ha tenido conocimiento de una investigación limitada sobre la
    incidencia del cáncer entre trabajadores expuestos a acetaldehído y
    otras sustancias.

         Según pruebas indirectas, el acetaldehído participa como
    metabolito potencialmente tóxico en la inducción de las afecciones
    hepáticas, la congestión facial y las alteraciones del desarrollo
    asociadas con el alcohol.

    9.  Evaluación de los riesgos para la salud humana y los efectos en el
        medio ambiente

         Los estudios efectuados con animales indican que la toxicidad
    aguda del acetaldehído por inhalación o por vía oral es baja.  Según
    las investigaciones con sujetos humanos y con animales, esa sustancia
    es algo irritante para los ojos y las vías respiratorias superiores. 
    Esos mismos efectos se han apreciado en voluntarios a los que se
    administró acetaldehído (sección 1.8).  Se ha observado eritema
    cutáneo consiguiente a las pruebas de parche en sujetos humanos. 
    Aunque se ha identificado un posible mecanismo, los datos de que se
    dispone son insuficientes para calcular el potencial del acetaldehído
    como inductor de sensibilización.

         Existe poca información sobre los efectos del acetaldehído
    ingerido.  Tras administrar diariamente a ratas por vía oral 675 mg/kg
    de peso corporal (NOEL = 125 mg/kg de peso corporal) se observó un
    aumento liminar de la hiperqueratosis en la parte anterior del
    estómago.  En las ratas que ingirieron durante seis meses con el agua
    de beber dosis aproximadas de 40 mg/kg de peso corporal hubo un
    aumento de la síntesis de colágeno en el hígado, cuya significación
    está por dilucidar.

         Los estudios de inhalación con ratas y hámsters permiten afirmar
    que el tejido sensible es el de las vías respiratorias superiores.  La
    concentración más baja a la que se observaron efectos fue 437 mg/m3
    durante cinco semanas.  El NOEL identificado del tracto respiratorio
    fue 275 mg/m3 en ratas expuestas durante cuatro semanas y
    700 mg/m3 en hámsters expuestos durante 13 semanas.

         A las concentraciones que producen daños en los tejidos del
    tracto respiratorio se observaron aumentos de la incidencia del
    adenocarcinoma nasal y del carcinoma de células escamosas en la rata,
    y de los carcinomas laríngeos y nasales en el hámster.

         Hay indicios de que el acetaldehído produce  in vivo
    alteraciones genéticas en las células somáticas.

         No se dispone de datos suficientes para determinar si el
    acetaldehído tiene efectos en la reproducción y el desarrollo o en el
    estado neurológico o inmunológico de la población general o de la que
    está particularmente expuesta por razón de su trabajo.

         A partir de datos sobre la acción irritante en sujetos humanos se
    ha considerado que la concentración tolerable es de 2 mg/m3.  El
    mecanismo de inducción de tumores por el acetaldehído no está bien
    estudiado.  En consecuencia, se han adoptado dos criterios
    orientativos a ese respecto; a saber, la determinación de una
    concentración tolerable obtenida dividiendo un nivel de efecto
    irritante en el tracto respiratorio de los roedores por un factor de
    incertidumbre, y la estimación del riesgo de cáncer mediante
    extrapolación linear.  La concentración tolerable resulta ser de
    0,3 mg/m3.  Las concentraciones asociadas con un aumento del riesgo
    permanente de 10-5 son de 11-65 µg/m3.

         La escasez de datos impide llegar a conclusiones definitivas
    sobre los riesgos potenciales del acetaldehído para la biota en el
    medio ambiente.  Sin embargo, basándose en la breve vida media del
    acetaldehído en el aire y en el agua, asi como en el hecho de que es
    fácilmente biodegradable, cabe afirmar que los efectos de esa
    sustancia en los organismos terrestres y acuáticos son escasos,
    excepto posiblemente con ocasión de descargas industriales o vertidos.

    See Also:
       Toxicological Abbreviations
       Acetaldehyde (HSG 90, 1995)
       Acetaldehyde (ICSC)
       ACETALDEHYDE (JECFA Evaluation)
       Acetaldehyde (IARC Summary & Evaluation, Volume 71, 1999)