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

    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
    environment. Supporting activities include the development of
    epidemiological, experimental laboratory, and risk-assessment methods
    that could produce internationally comparable results, and the
    development of manpower in the field of toxicology. Other activities
    carried out by the IPCS include the development of know-how for coping
    with chemical accidents, coordination of laboratory testing and
    epidemiological studies, and promotion of research on the mechanisms
    of the biological action of 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.

                                      *     *     *

         A detailed data profile and a legal file can be obtained from the
    International Register of Potentially Toxic Chemicals, Case postale
    356, 1219 Chtelaine, 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



         In 1973 the WHO Environmental Health Criteria Programme was
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    *    Summary - a review of the salient facts and the risk evaluation
         of the chemical
    *    Identity - physical and chemical properties, analytical methods
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         JECFA, JMPR

    Selection of chemicals

         Since the inception of the EHC Programme, the IPCS has
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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 tampar 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 g/m3.  Concentrations in water are generally less than
    0.1 g/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 g/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 g/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 g/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 400C, 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                20.2C
    Melting point                             -123.5C
    Octanol/water partition coefficient as    0.63
    log Pow
    Flash point, closed cup                   -38C
    Autoignition temperature                  185-193C
    Explosion limits of mixtures with air     4.5-60.5 vol % acetaldehyde
    Vapour pressure at   -50C                2.5 kPa
                           0C                44.0 kPa
                       20.16C                101.3 kPa
    Specific gravity (20/4)                   0.778
    Relative vapour density                   1.52
    Refractive index 20/D                     1.33113
    Dissociation constant at 0C, 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 (0/20C) (US NRC, 1981).

    2.3  Conversion factors

    1 mg acetaldehyde/m3 air    =  0.56 ppm at 25C 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 g/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 g/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                                     g/m3         litre         smog and automobile         (1983)

    Air      collection in a 2,4-DNPH            HPLC with             < 18 g/m3    < 20 litre    suitable for long-term      Tejada (1986)
             coated Sep-PAK cartridge,           spectrophotometric                                sampling at low g/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 g/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 g/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 g/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 g         --            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 g/       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 g 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 g/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                                                          g/litre levels

    Water      collection of aqueous solution      HS-GC-FID            25 g/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 litre    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 g 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 g/      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 g 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 g 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 g per    50-100          designed for microassays   Ung-Chhun &
            in the presence of ammonium ion     fluorescence          sample        litre          with negligible            Collins (1987)
            propionaldehyde used as internal    detection                                           interference

    Blood   collection in an organic solution   HPLC with             > 0.13 g     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 g/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 26-153C by Atkinson & Pitts
    (1978).  At 26C, 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 25C, 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 25C.  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 0C, the fraction of acetaldehyde hydrated is
    0.73; at 25C, 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 20C 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 g/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 g/m3 and 1.62-6.12 g/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 g/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 g/m3, detection limit:
    0.29 g/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 g/m3, with a mean
    minimum concentration in winter of 1.8 g/m3 and a mean maximum
    value in summer of 15.1 g/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 g/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 g/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 g/m3 (number of
    sites sampled unspecified) (Japan Environment Agency, 1989).

         The mean concentration of acetaldehyde was 2 g/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 g/m3 (13 ppb) with average values
    at the various locations ranging from 5.2 to 8.6 g/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 g/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 g/ml in ice fog (Alaska), 0 to 0.11 g/ml in rain (CA), 0 to
    0.59 g/ml in cloud (CA), 0.10 to 0.11 g/ml in mist (CA), and 0.006
    to 0.17 g/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 g/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 g/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 g per cigarette)
    and marijuana (1200 g/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 g/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 g/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 g/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 g/m3, the mean intake of
    acetaldehyde from ambient air for the general population is estimated
    to be 1.7 g/kg body weight per day.

         Limited identified data on concentrations of acetaldehyde in
    drinking-water indicate that they are generally less than 0.1 g/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 g/litre, the
    estimated intake of acetaldehyde from drinking-water for the general
    population would not exceed 0.002 g/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 g/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 (Hellstrm-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 37C 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 (Nimela 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 37C  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 37C, 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 g acetaldehyde/m3 applied for 5 h, whereas 1.08 g
    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 g/m3  (A. tenuis) to 0.09 g/m3  (C. gloeosporioides).
    Acetaldehyde remained lethal for the five fungi, even when the
    treatment lasted only 20 min (0.90 g/m3 for  P. vagabunda, C.
     malicorticis, and  A. tenuis, and 0.36 g/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 g/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 g acetaldehyde/m3  and a 3-4 h exposure were
    required for 100% mortality.  A similar treatment (0.27-0.36 g/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 g/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 g/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 identif