IPCS INCHEM Home


    UNITED NATIONS ENVIRONMENT PROGRAMME
    INTERNATIONAL LABOUR ORGANISATION
    WORLD HEALTH ORGANIZATION


    INTERNATIONAL PROGRAMME ON CHEMICAL SAFETY



    ENVIRONMENTAL HEALTH CRITERIA 191





    Acrylic Acid








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


    First draft prepared at the National Institute of Health Sciences,
    Tokyo, Japan, and the Institute of Terrestrial Ecology, Monk's Wood,
    United Kingdom


    Published under the joint sponsorship of the United Nations
    Environment Programme, the International Labour Organisation, and the
    World Health Organization, and produced within the framework of the
    Inter-Organization Programme for the Sound Management of Chemicals.


    World Health Organization
    Geneva, 1997

         The International Programme on Chemical Safety (IPCS) is a joint
    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

    Acrylic Acid

    (Environmental health criteria ; 191)

    1.Acrylates - adverse affects      2.Acrylates - toxicity
    3.Environmental exposure           4.Occupational exposure
    I.Series

    ISBN 92 4 157191 8                 (NLM Classification: QV 50)
    ISSN 0250-863X

         The World Health Organization welcomes requests for permission to
    reproduce or translate its publications, in part or in full.
    Applications and enquiries should be addressed to the Office of
    Publications, World Health Organization, Geneva, Switzerland, which
    will be glad to provide the latest information on any changes made to
    the text, plans for new editions, and reprints and translations
    already available.

    (c) World Health Organization 1997

         Publications of the World Health Organization enjoy copyright
    protection in accordance with the provisions of Protocol 2 of the
    Universal Copyright Convention. All rights reserved. The designations
    employed and the presentation of the material in this publication do
    not imply the expression of any opinion whatsoever on the part of the
    Secretariat of the World Health Organization concerning the legal
    status of any country, territory, city or area or of its authorities,
    or concerning the delimitation of its frontiers or boundaries. The
    mention of specific companies or of certain manufacturers' products
    does not imply that they are endorsed or recommended by the World
    Health Organization in preference to others of a similar nature that
    are not mentioned. Errors and omissions excepted, the names of
    proprietary products are distinguished by initial capital letters.

    CONTENTS

    ENVIRONMENTAL HEALTH CRITERIA FOR ACRYLIC ACID

    PREAMBLE

    ABBREVIATIONS

    1. SUMMARY AND RECOMMENDATIONS

    2. IDENTITY, PHYSICAL AND CHEMICAL PROPERTIES, AND ANALYTICAL
         METHODS

         2.1. Identity
               2.1.1. Primary constituent
               2.1.2. Technical product
         2.2. Physical and chemical properties
               2.2.1. Physical properties
               2.2.2. Chemical properties
         2.3. Conversion factors
         2.4. Analytical methods
               2.4.1. In air
               2.4.2. In industrial effluents
               2.4.3. In polyacrylate materials
               2.4.4. In biological samples

    3. SOURCES OF HUMAN AND ENVIRONMENTAL EXPOSURE

         3.1. Natural occurrence
         3.2. Anthropogenic sources
               3.2.1. Production levels and processes
                       3.2.1.1   Manufacturing process
                       3.2.1.2   Impurities
                       3.2.1.3   Other sources
                       3.2.1.4   Production data
               3.2.2. Experimental production of acrylic
                       acid by bacterial isolates
               3.2.3. Uses

    4. ENVIRONMENTAL TRANSPORT, DISTRIBUTION AND TRANSFORMATION

         4.1. Transport and distribution between media
         4.2. Transformation
               4.2.1. Abiotic degradation
               4.2.2. Biodegradation
                       4.2.2.1   Aerobic biodegradation
                       4.2.2.2   Anaerobic biodegradation
               4.2.3. Bioaccumulation and biomagnification

    5. ENVIRONMENTAL LEVELS AND HUMAN EXPOSURE

         5.1. Environmental levels
         5.2. General population exposure
         5.3. Occupational exposure during manufacture,
               formulation or use

    6. KINETICS AND METABOLISM

         6.1. Human studies
         6.2. Studies on experimental animals
               6.2.1. Absorption, distribution and excretion
                       6.2.1.1   Oral exposure
                       6.2.1.2   Inhalation exposure
                       6.2.1.3   Dermal exposure
                                 6.2.1.4   Intravenous administration
               6.2.2. Metabolism
                       6.2.2.1    In vitro investigations
                       6.2.2.2    In vivo investigations
                       6.2.2.3   Metabolic pathways

    7. EFFECTS ON EXPERIMENTAL ANIMALS AND  IN VITRO TEST SYSTEMS

         7.1. Single exposure
         7.2. Irritation and sensitization
               7.2.1. Eye irritation
               7.2.2. Skin irritation and sensitization
                       7.2.2.1   Skin irritation
                       7.2.2.2   Skin sensitization
               7.2.3. Upper respiratory tract irritation
         7.3. Short-term exposure
               7.3.1. Oral
               7.3.2. Inhalation
         7.4. Long-term exposure
         7.5. Reproduction, embryotoxicity and teratogenicity
               7.5.1. Reproduction
               7.5.2. Embryotoxicity and teratogenicity
                       7.5.2.1   Oral
                       7.5.2.2   Inhalation
                       7.5.2.3   Intraperitoneal
         7.6. Mutagenicity and related end-points
               7.6.1.  In vitro and insect studies
               7.6.2.  In vivo mammalian studies
         7.7. Carcinogenicity
         7.8. Other  studies
         7.9. Factors modifying toxicity

    8. EFFECTS ON HUMANS

         8.1. General population exposure
               8.1.1. Acute toxicity
                       8.1.1.1   Poisoning accidents

         8.2. Occupational exposure
               8.2.1. Poisoning accidents
               8.2.2. Effects of short- and long-term exposure

    9. EFFECTS ON ORGANISMS IN THE ENVIRONMENT

         9.1. Microorganisms
         9.2. Aquatic organisms
         9.3. Terrestrial organisms

    10. EVALUATION OF HUMAN HEALTH RISKS AND EFFECTS ON THE ENVIRONMENT

         10.1. Evaluation of human health risks
               10.1.1. Exposure of the general population
               10.1.2. Occupational exposure
               10.1.3. Toxic effects
                       10.1.3.1  Carcinogenic and mutagenic effects
                       10.1.3.2  Non-cancer effects
               10.1.4. Risk evaluation
                       10.1.4.1  Inhalation exposure
                       10.1.4.2  Oral exposure
         10.2. Evaluation of effects on the environment
               10.2.1. Exposure
               10.2.2. Effects
               10.2.3. Risk evaluation

    11. CONCLUSIONS AND RECOMMENDATIONS FOR PROTECTION OF HUMAN HEALTH

         11.1. Conclusions
         11.2. Recommendations for protection of human health

    12. FUTURE RESEARCH

    13. PREVIOUS EVALUATIONS BY INTERNATIONAL BODIES

    14. REFERENCES

    RESUME ET RECOMMANDATIONS

    RESUMEN Y RECOMENDACIONES
    

    NOTE TO READERS OF THE CRITERIA MONOGRAPHS

         Every effort has been made to present information in thecriteria
    monographs as accurately as possible without unduly delaying their
    publication.  In the interest of all users of the Environmental Health
    Criteria monographs, readers are 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 Châtelaine, Geneva, Switzerland (telephone no. + 41 22 -
    9799111, fax no. + 41 22 - 7973460, E-mail irptc@unep.ch).

                                 *     *     *

         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.

                                 *     *     *

         The Federal Ministry for the Environment, Nature Conservation and
    Nuclear Safety, Germany, provided financial support for this
    publication.

    Environmental Health Criteria

    PREAMBLE

    Objectives

         In 1973 the WHO Environmental Health Criteria Programme was
    initiated with the following objectives:

    (i)     to assess information on the relationship between exposure to
            environmental pollutants and human health, and to provide
            guidelines for setting exposure limits;

    (ii)    to identify new or potential pollutants;

    (iii)   to identify gaps in knowledge concerning the health effects of
            pollutants;

    (iv)    to promote the harmonization of toxicological and
            epidemiological methods in order to have internationally
            comparable results.

         The first Environmental Health Criteria (EHC) monograph, on
    mercury, was published in 1976 and since that time an ever-increasing
    number of assessments of chemicals and of physical effects have been
    produced.  In addition, many EHC monographs have been devoted to
    evaluating toxicological methodology, e.g., for genetic, neurotoxic,
    teratogenic and nephrotoxic effects.  Other publications have been
    concerned with epidemiological guidelines, evaluation of short-term
    tests for carcinogens, biomarkers, effects on the elderly and so
    forth.

         Since its inauguration the EHC Programme has widened its scope,
    and the importance of environmental effects, in addition to health
    effects, has been increasingly emphasized in the total evaluation of
    chemicals.

         The original impetus for the Programme came from World Health
    Assembly resolutions and the recommendations of the 1972 UN Conference
    on the Human Environment.  Subsequently the work became an integral
    part of the International Programme on Chemical Safety (IPCS), a
    cooperative programme of UNEP, ILO and WHO.  In this manner, with the
    strong support of the new partners, the importance of occupational
    health and environmental effects was fully recognized. The EHC
    monographs have become widely established, used and recognized
    throughout the world.

         The recommendations of the 1992 UN Conference on Environment and
    Development and the subsequent establishment of the Intergovernmental
    Forum on Chemical Safety with the priorities for action in the six
    programme areas of Chapter 19, Agenda 21, all lend further weight to
    the need for EHC assessments of the risks of chemicals.

    Scope

         The criteria monographs are intended to provide critical reviews
    on the effect on human health and the environment of chemicals and of
    combinations of chemicals and physical and biological agents.  As
    such, they include and review studies that are of direct relevance for
    the evaluation.  However, they do not describe  every study carried
    out.  Worldwide data are used and are quoted from original studies,
    not from abstracts or reviews.  Both published and unpublished reports
    are considered and it is incumbent on the authors to assess all the
    articles cited in the references.  Preference is always given to
    published data.  Unpublished data are only used when relevant
    published data are absent or when they are pivotal to the risk
    assessment.  A detailed policy statement is available that describes
    the procedures used for unpublished proprietary data so that this
    information can be used in the evaluation without compromising its
    confidential nature (WHO (1990) Revised Guidelines for the Preparation
    of Environmental Health Criteria Monographs. PCS/90.69, Geneva, World
    Health Organization).

         In the evaluation of human health risks, sound human data,
    whenever available, are preferred to animal data.  Animal and
     in vitro studies provide support and are used mainly to supply
    evidence missing from human studies.  It is mandatory that research on
    human subjects is conducted in full accord with ethical principles,
    including the provisions of the Helsinki Declaration.

         The EHC monographs are intended to assist national and
    international authorities in making risk assessments and subsequent
    risk management decisions.  They represent a thorough evaluation of
    risks and are not, in any sense, recommendations for regulation or
    standard setting.  These latter are the exclusive purview of national
    and regional governments.

    Content

         The layout of EHC monographs for chemicals is outlined
    below.

    *    Summary - a review of the salient facts and the risk evaluation
         of the chemical
    *    Identity - physical and chemical properties, analytical methods
    *    Sources of exposure
    *    Environmental transport, distribution and transformation
    *    Environmental levels and human exposure
    *    Kinetics and metabolism in laboratory animals and humans
    *    Effects on laboratory mammals and  in vitro test systems
    *    Effects on humans
    *    Effects on other organisms in the laboratory and field
    *    Evaluation of human health risks and effects on the environment

    *    Conclusions and recommendations for protection of human health
         and the environment
    *    Further research
    *    Previous evaluations by international bodies, e.g., IARC, JECFA,
         JMPR

    Selection of chemicals

         Since the inception of the EHC Programme, the IPCS has organized
    meetings of scientists to establish lists of priority chemicals for
    subsequent evaluation.  Such meetings have been held in: Ispra, Italy,
    1980; Oxford, United Kingdom, 1984; Berlin, Germany, 1987; and North
    Carolina, USA, 1995. The selection of chemicals has been based on the
    following criteria: the existence of scientific evidence that the
    substance presents a hazard to human health and/or the environment;
    the possible use, persistence, accumulation or degradation of the
    substance shows that there may be significant human or environmental
    exposure; the size and nature of populations at risk (both human and
    other species) and risks for environment; international concern, i.e.
    the substance is of major interest to several countries; adequate data
    on the hazards are available.

         If an EHC monograph is proposed for a chemical not on the
    priority list, the IPCS Secretariat consults with the Cooperating
    Organizations and all the Participating Institutions before embarking
    on the preparation of the monograph.

    Procedures

         The order of procedures that result in the publication of an EHC
    monograph is shown in the flow chart.  A designated staff member of
    IPCS, responsible for the scientific quality of the document, serves
    as Responsible Officer (RO).  The IPCS Editor is responsible for
    layout and language.  The first draft, prepared by consultants or,
    more usually, staff from an IPCS Participating Institution, is based
    initially on data provided from the International Register of
    Potentially Toxic Chemicals, and reference data bases such as Medline
    and Toxline.

         The draft document, when received by the RO, may require an
    initial review by a small panel of experts to determine its scientific
    quality and objectivity.  Once the RO finds the document acceptable as
    a first draft, it is distributed, in its unedited form, to well over
    150 EHC contact points throughout the world who are asked to comment
    on its completeness and accuracy and, where necessary, provide
    additional material.  The contact points, usually designated by
    governments, may be Participating Institutions, IPCS Focal Points, or
    individual scientists known for their particular expertise.  Generally
    some four months are allowed before the comments are considered by the
    RO and author(s).  A second draft incorporating comments received and
    approved by the  Director,  IPCS, is then  distributed to Task Group
    members, who carry out the peer review, at least six weeks before
    their meeting.

    FIGURE 1

         The Task Group members serve as individual scientists, not as
    representatives of any organization, government or industry.  Their
    function is to evaluate the accuracy, significance and relevance of
    the information in the document and to assess the health and
    environmental risks from exposure to the chemical.  A summary and
    recommendations for further research and improved safety aspects are
    also required.  The composition of the Task Group is dictated by the
    range of expertise required for the subject of the meeting and by the
    need for a balanced geographical distribution.

         The three cooperating organizations of the IPCS recognize the
    important role played by nongovernmental organizations.
    Representatives from relevant national and international associations
    may be invited to join the Task Group as observers.  While observers
    may provide a valuable contribution to the process, they can only
    speak at the invitation of the Chairperson. Observers do not
    participate in the final evaluation of the chemical; this is the sole
    responsibility of the Task Group members.  When the Task Group
    considers it to be appropriate, it may meet  in camera.

         All individuals who as authors, consultants or advisers
    participate in the preparation of the EHC monograph must, in addition
    to serving in their personal capacity as scientists, inform the RO if
    at any time a conflict of interest, whether actual or potential, could
    be perceived in their work.  They are required to sign a conflict of
    interest statement. Such a procedure ensures the transparency and
    probity of the process.

         When the Task Group has completed its review and the RO is
    satisfied as to the scientific correctness and completeness of the
    document, it then goes for language editing, reference checking, and
    preparation of camera-ready copy.  After approval by the Director,
    IPCS, the monograph is submitted to the WHO Office of Publications for
    printing.  At this time a copy of the final draft is sent to the
    Chairperson and Rapporteur of the Task Group to check for any errors.

         It is accepted that the following criteria should initiate the
    updating of an EHC monograph: new data are available that would
    substantially change the evaluation; there is public concern for
    health or environmental effects of the agent because of greater
    exposure; an appreciable time period has elapsed since the last
    evaluation.

         All Participating Institutions are informed, through the EHC
    progress report, of the authors and institutions proposed for the
    drafting of the documents.  A comprehensive file of all comments
    received on drafts of each EHC monograph is maintained and is
    available on request.  The Chairpersons of Task Groups are briefed
    before each meeting on their role and responsibility in ensuring that
    these rules are followed.

    WHO TASK GROUP ON ENVIRONMENTAL HEALTH CRITERIA FOR ACRYLIC ACID

     Members

    Dr B.I. Ghanayem, National Institute of Environmental Health
         Sciences, Research Triangle Park, North Carolina, USA

    Dr D. Guth, Office of Research and Development, National Centre
         for Environmental Assessment, Research Triangle Park North
         Carolina, USA

    Mr L. Heiskanen, Environmental Health and Safety Unit,
         Department of Health and Family Services, Canberra, Australia

    Mr P.D. Howe, Institute of Terrestrial Ecology, Monks Wood,
         Abbots Ripton, Huntingdon, United Kingdom ( Co-rapporteur)

    Dr P. Lundberg, Department of Toxicology and Chemistry,
         National Institute for Working Life, Sweden ( Chairman)

    Dr K. Rydzynski, The Nofer Institute of Occupational Medicine,
         Lodz, Poland ( Co-rapporteur)

    Dr R.O. Shillaker, Pesticides Safety Directorate, Ministry of
         Agriculture, Fisheries & Food, United Kingdom

    Dr S.A. Soliman, Department of Pesticide Chemistry, Faculty of
         Agriculture, Alexandria University, Alexandria, Egypt

     Observers

    Dr M. Wooder, Rohm and Haas Uk, Ltd., Croydon, Surrey, United
         Kingdom (representing the American Industrial Health Council)

    Dr A. Lombard, Service Hygiène Industrielle Toxicologique, ELF-
         ATOCHEM, Paris, France (representing the Centre for Ecotoxicology
         and Toxicology of Chemicals)

     Secretariat

    Dr B.H. Chen, International Programme on Chemical Safety, World
         Health Organization, Geneva, Switzerland ( Secretary)

    IPCS TASK GROUP ON ENVIRONMENTAL HEALTH CRITERIA FOR ACRYLIC ACID

         A WHO Task Group on Environmental Health Criteria for Acrylic
    Acid met at the Institute of Terrestrial Ecology, Monks Wood,
    Huntington, United Kingdom, from 16 to 19 April 1996.  Dr S. Dobson
    opened the meeting and welcomed the participants on behalf of the
    Institute.  Dr B.H. Chen, IPCS, welcomed the participants on behalf of
    the Director, IPCS, and the three IPCS cooperating organizations
    (UNEP/ILO/WHO).  The Task Group reviewed and revised the draft 
    monograph and made an evaluation of the risks for human health and the
    environment from exposure to acrylic acid.

         Dr K. Rydzynski, the Nofer Institute of Occupational Medicine,
    Poland, prepared the first draft of this monograph.  Dr R.O.
    Shillaker, Pesticides Safety Directorate, Ministry of Agriculture,
    Fisheries and Food, United Kingdom, contributed to the preparation of
    the first draft.  The second draft was prepared by Dr K. Rydzynski
    incorporating comments received following the circulation of the first
    draft to the IPCS Contact Points for Environmental Health Criteria. 
    Dr D. Guth, National Centre for Environmental Protection, USA,
    contributed to the preparation of the final text of the evaluation. 
    The meeting was chaired by Dr P. Lundberg, National Institute for
    Working Life, Sweden.

         Dr B.H. Chen and Dr P.G. Jenkins, IPCS Central Unit, were
    responsible for the overall scientific content and technical editing,
    respectively.

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

    ABBREVIATIONS

    ACGIH          American Conference of Governmental Industrial
                   Hygienists
    CHO            Chinese hamster ovary
    EC50           median effective concentration
    FID            flame ionization detector
    GC             gas chromatography
    GSH            reduced glutathione
    GV             guidance value
    HPLC           high performance liquid chromatography
    LC50           median lethal concentration
    LD50           median lethal dose
    LOAEL          lowest-observed-adverse-effect level
    LOEL           lowest-observed-effect concentration
    NMR            nuclear magnetic resonance
    NOAEL          no-observed-adverse-effect level
    NOEC           no-observed-effect concentration
    NOEL           no-observed-effect level
    OSHA           Occupational Safety and Health Administration (USA)
    TCA            tricarboxylic acid cycle
    TI             tolerable intake
    TT             toxicity threshold
    UDS            unscheduled DNA synthesis
    
    1.  SUMMARY AND RECOMMENDATIONS

         Acrylic acid is a colourless liquid, with an irritating acrid
    odour, at room temperature and pressure. The odour threshold of
    acrylic acid is low (0.20-3.14 mg/m3). It is miscible with water and
    most organic solvents.

         Acrylic acid is commercially available in two grades; technical
    grade and glacial grade. Acrylic acid polymerizes easily when exposed
    to heat, light or metals, and a polymerization inhibitor is therefore
    added to commercial products.

         The worldwide production of acrylic acid in 1994 was estimated to
    be approximately 2 million tonnes. It is used primarily as a starting
    material in the production of acrylic esters as a monomer for
    polyacrylic acid and salts and as a co-monomer with acrylamide for
    polymers used as flocculants, with ethylene for ion-exchange resin
    polymers, with methyl ester for polymers, and with itatonic acid for
    other co-polymers.

         Acrylic acid residues in air and other media can be quantified by
    means of gas chromatographic, high performance liquid chromatographic
    and polarographic techniques. The detection limits of these methods
    are 14 ppm in air and 1 ppm in other media.

         Acrylic acid has been reported to occur naturally in marine algae
    and has been found in the rumen fluid of sheep.

         Being miscible with water, acrylic acid would not be expected to
    adsorb significantly to soil or sediment. Under soil conditions,
    chemicals with low Henry's Law constants are essentially non-volatile.
    However, the vapour pressure of acrylic acid suggests that it
    volatilizes from surface and dry soil.

         Acrylic acid emitted into the atmosphere will react with
    photochemically produced hydroxyl radicals and ozone, resulting in
    rapid degradation. There is no potential for long-range atmospheric
    transport of acrylic acid because it has an atmospheric lifetime of
    less than one month.

         Acrylic acid may be formed by hydrolysis of acrylamide monomer
    from industrial waste in soil, especially under aerobic conditions.

         When released into water, acrylic acid readily biodegrades. The
    fate of acrylic acid in water depends on chemical and microbial
    degradation. Acrylic acid is rapidly oxidized in water and can
    therefore potentially deplete oxygen if discharged in large quantities
    into a body of water. Acrylic acid has been shown to be degraded under
    both aerobic and anaerobic conditions.

         No quantitative data on levels of acrylic acid in ambient air,
    drinking-water or soil are available. However, acrylic acid occurs in
    wastewater effluent from its production via the oxidation of
    propylene.

         No data on general population exposure are available. However,
    consumers may be exposed to unreacted acrylic acid in household goods
    such as water-based paints. People living in the vicinity of plants
    producing acrylic acid or its esters or polymers may be exposed to
    acrylic acid in the ambient air. A potential source of internal
    exposure to acrylic acid may result from metabolism of absorbed
    acrylic acid esters.

         Inhalation and contact with skin are important routes of
    occupational exposure.

         Regardless of the route of exposure, acrylic acid is rapidly
    absorbed and metabolized. It is extensively metabolized, mainly to
    3-hydroxy propionic acid, CO2 and mercapturic acid, which are
    eliminated in the expired air and urine. Owing to its rapid metabolism
    and elimination, the half-life of acrylic acid is short (minutes) and
    therefore it has no potential for bioaccumulation.

         Although a wide range of LD50 values has been reported, most
    data indicate that acrylic acid is of low to moderate acute toxicity
    by the oral route and moderate acute toxicity by the inhalation or
    dermal route.

         Acrylic acid is corrosive or irritant to skin and eyes. It is
    unclear what concentration is non-irritant. It is also a strong
    irritant to the respiratory tract.

         Positive and negative skin sensitization results have been
    reported with acrylic acid, but it appears that the positive results
    may be due to an impurity.

         In drinking-water studies on rats, the no-observed-adverse-effect
    level (NOAEL) was 140 mg/kg body weight per day for decreased body
    weight gain in a 12-month study and 240 mg/kg body weight per day for
    histopathological changes in the stomach. A chronic drinking-water
    study on rats showed no effect at the highest dose tested (78 mg/kg
    body weight per day). A lowest-observed-adverse-effect level (LOAEL)
    of 15 mg/m3 (5 ppm) by the inhalation route was observed in mice
    exposed to acrylic acid for 90 days, based on very mild nasal lesions
    in females at this level. Nasal effects in rats were observed at
    225 mg/m3 (75 ppm), but not at 15 or 75 mg/m3 (5 or 25 ppm).

         Available reproduction studies indicate that acrylic acid is not
    teratogenic and has no effect on reproduction.

         Both positive and negative results have been obtained in
     in vitro genotoxicity tests. An  in vivo bone marrow chromosome
    aberration assay gave negative results. No firm conclusions can be
    drawn from an  in vivo DNA binding study or from a dominant lethal
    assay.

         Available data do not provide evidence for an indication of
    carcinogenicity of acrylic acid, but the data are inadequate to
    conclude that no carcinogenic hazard exist.

         There have been no reports of poisoning incidents in the general
    population. No occupational epidemiological studies have been
    reported.

         Because acrylic acid toxicity occurs at the site of contact,
    separate guidance values are recommended for oral and inhalation
    exposure. Guidance values of 9.9 mg/litre for drinking-water and
    54 µg/m3 for ambient air for the general population are proposed.

         The toxicity of acrylic acid to bacteria and soil microorganisms
    is low.

         Algae are the most sensitive group of aquatic organisms studied,
    with EC50 values, based on growth, ranging from 0.04 to 63 mg/litre
    and a no-observed-effect concentration (NOEC) for the most sensitive
    species of 0.008 mg/litre. EC50 values (based on immobilization) for
     Daphnia magna are 54 mg/litre (24 h) and 95 mg/litre (48 h). Acrylic
    acid is more toxic to daphnids than is the alkaline salt. Acute
    toxicity studies with fish have yielded results ranging from
    27 mg/litre (96-h LC50) for the rainbow trout to 315 mg/litre (72-h
    LC50) for the golden orfe. The 96-h NOEC for acrylic acid toxicity to
    rainbow trout was found to be 6.3 mg/litre, based on a lack of
    sublethal/behavioural responses.

         Because of its low octanol-water partition coefficient, acrylic
    acid is unlikely to bioconcentrate in aquatic organisms. There have
    been no reports of biomagnification in food chains.

         No data are available concerning the effects of acrylic acid on
    terrestrial organisms.
    

    2.  IDENTITY, PHYSICAL AND CHEMICAL PROPERTIES, AND ANALYTICAL METHODS

    2.1  Identity

    2.1.1  Primary constituent

    Common name:             acrylic acid

    CAS name:                2-propenoic acid

    CAS registry number:     79-10-7

    EEC No:                  607-061-00-8

    DOT UN:                  22-18-29

    RTECS Number:            AS 4375000

    Synonyms:                acroleic acid (Sax & Lewis, 1989)
                             2-propenoic acid (Sax, 1984)
                             vinylformic acid (Sittig, 1985)
                             propene acid (Sax, 1984)

                             ethylenecarboxylic acid
                             (Verschueren, 1983)
                             UN 2218
                             propenoic acid (Weast et al., 1989)
                             ethene carboxylic acid (IUPAC name)

    Chemical formula:        C3H4O2

    Chemical structure:

    CHEMICAL STRUCTURE 1

    Relative molecular mass: 72.06

    2.1.2  Technical product

         Acrylic acid is commercially available in two grades: technical
    grade (94%) for esterification and glacial grade (98-99.5% by weight
    and a maximum of 0.3% water by weight) for production of water-soluble
    resins (IARC, 1979; CHRIS, 1989). Acrylic acid polymerizes easily when
    exposed to heat, light or metals, and so a polymerization inhibitor is
    added to commercial acrylic acid to prevent the strong exothermic
    polymerization (NLM, 1989). The inhibitors that are usually used in
    acrylic acid preparations are the monomethyl ether of hydroquinone
    (methoxyphenol) at 200 ± 20 ppm, phenothiazine at 0.1% and
    hydroquinone at 0.1%. Methylene blue at 0.5 to 1.0% and  N,N'-
    diphenyl- p-phenylenediamine at 0.05% can also be used (IARC, 1979;
    CHRIS, 1989; OHM/TADS, 1989; BASF, 1993).

    2.2  Physical and chemical properties

    2.2.1  Physical properties

         Acrylic acid is a colourless liquid at room temperature and
    pressure (IARC, 1979; Windholz, 1983; CHRIS, 1985). It has an
    irritating acrid odour and it is totally miscible with water and most
    organic solvents. Some of the most important physical properties of
    acrylic acid are summarized in Table 1.



        Table 1.  Physical and chemical properties of acrylic acid

                                                                                                                              

    Property                                      Value              References
                                                                                                                              

    Odour threshold concentration (mg/m3)         0.20-3.14          Fazzalari, 1978; Amoore & Hautala, 1983;
                                                                     Ruth, 1986; Grudzinski, 1988; HSDB, 1989

    Melting point (°C at 1 atm)                   12.3-14.0          CHRIS, 1989; Weast et al., 1989
    Boiling point (°C at 1 atm)                   141.3-141.6        CHRIS, 1989; Weast et al., 1989
    Flash point (°C)
         open cup
         closed cup                               54.0-68.3          IARC, 1979; Kirk-Othmer, 1984; Sax & Lewis 1989;
                                                  46-48.5            Elf Atochem, 1992; BASF, 1994a

    Autoignition temperature (°C)                 390-446            IARC, 1979; HSDB, 1989; BASF, 1992; Elf Atochem, 1992

    Flammable limits (%)
         lower                                    28                 HSDB, 1989
         upper

    Burning rate (mm/min)                         1.6                CHRIS, 1989

    Specific gravity (g/ml at 20°C)               1.0497-1.0511      IARC, 1979; CHRIS, 1989; Weast et al., 1989

    Relative vapour density (air =1 at 20°C)      2.5                HSDB, 1989

    Viscosity (mPa.s at  20°C)                    1.22-1.30          BASF, 1992; Elf Atochem, 1992

    Saturated concentration in air
     (g/m3 at 20°C)                               22.8               Verschueren, 1983

    Volatility (mmHg at 20°C)                     3.1; 7.76          Riddick et al., 1986

    Vapour pressure (mmHg)
         at 39°C                                  10                 OHM/TADS, 1989
         at 75°C                                  60
                                                                                                                              

    Table 1.  (contd)

                                                                                                                              

    Property                                      Value              References
                                                                                                                              

    Henry's law constant (atm.m3/mol)             3.2 × 10-7         Singh et al., 1984

    Surface tension (dyne/cm)                     28.1 at 30°C       Dean, 1987

    Heat of fusion (cal/g)                        30.03-37.03        CHRIS, 1989; Weast et al., 1989

    Heat of polymerization (cal/g)                -257               CHRIS, 1989

    Heat of combustion (cal/g)                    -327 at 25°C       Weast et al., 1989

    Heat of vaporization (cal/g)                  10.955             Weast et al., 1989

    Activated carbon absorbability (g/g)          0.129              Verschueren, 1983

    Partition coefficient (log Kow at 20-25°C)    0.161-0.46         Korenman & Lunicheva, 1972; GEMS, 1983; Hansch & Leo, 1987;
    BASF, 1988

    Dissociation constant (pKa at 25°C)           4.25               Weast et al., 1989

    Critical temperature (°C)                     342                CHRIS, 1985

    Critical pressure (atm)                       57                 CHRIS, 1985

    Solubility: in water and most organic         completely         Dean, 1987; Sax & Lewis, 1989; Weast et al., 1989
     solvents (alcohol, chloroform, benzene)      miscible

    Refractive index (nD20-25)                    1.4224-1.4185      Kirk-Othmer, 1984

    Maximum absorption (nm, in methanol)          252                Weast et al., 1989
                                                                                                                              
    

    2.2.2  Chemical properties

         Acrylic acid preparations containing polymerization inhibitors
    are reasonably stable when stored at 15-25°C and handled according to
    supplier's recommendations. Heating can cause vigorous polymerization
    in some circumstances. Acrylic acid reacts readily with free radicals
    and electrophilic or nucleophilic agents (Kirk-Othmer, 1984). It may
    polymerize in the presence of acids (sulfuric acid, chlorosulfonic
    acid), alkalis (ammonium hydroxide), amines (ethylenediamine,
    ethyleneimine, 2-aminoethanol), iron salts, elevated temperature,
    light, peroxides, and other compounds that form peroxides or free
    radicals. In the absence of an inhibitor, peroxides are formed when
    oxygen is sparged into acrylic acid. This mixture can undergo violent
    polymerization if heated to 60°C (CHRIS, 1989). The mechanism of auto-
    accelerating polymerization of acrylic acid in hexane-methanol
    solution, which can become explosive, has been studied by Bretherick
    (1985).

         Acrylic acid rapidly decomposes in the atmosphere by
    photochemical attack on the double bond (NLM, 1989; OHM/TADS, 1989).

         Acrylic acid is corrosive to many metals but not to stainless
    steel or aluminium (Kirk-Othmer, 1984; AAR, 1987).

    2.3  Conversion factors
         In air:
         1 ppm   = 3.0 mg/m3 (NLM, 1989)
         1 mg/m3 = 0.33 ppm (NLM, 1989)

    2.4  Analytical methods

    2.4.1  In air

         A summary of methods for the detection of acrylic acid in air is
    given in Table 2.



        Table 2.  Methods for the analysis of acrylic acid in air

                                                                                                                                                

    Sampling                 Analytical methods      Detectiona     Detection limit          Comment               Reference
    methods
                                                                                                                              

    Air samples absorbed     GC on a glass column    FID            33 mg/ml acetone         The method is         Vincent &
    on silica gel treated    packed with 1% FFAP                    (lower) to               significantly         Guient, 1982
    with  p-methoxyphenol     on Chromosorb T                        2084 mg/ml acetone       affected by high
    followed by desorption                                          (upper); this is         humidity. Samples
    with acetone (94%                                               equivalent to            can be stored for
    recovery)                                                       concentrations ranging   up to 11 days at
                                                                    from 0.5 ppm to 30 ppm   room temperature or
                                                                    (1.5-90 mg/m3) of        under refrigeration
                                                                    acrylic acid in a        without affecting
                                                                    48-litre sample volume   recovery. Recommended
                                                                                             as useful for
                                                                                             determining acrylic
                                                                                             acid in the
                                                                                             occupational
                                                                                             environment
                                                                                                                              

    Table 2.  (contd)

                                                                                                                              

    Sampling                 Analytical methods      Detectiona     Detection limit          Comment               Reference
    methods
                                                                                                                              

    Air samples              Reverse phase           UV detector    1 g per sample;          The sensitivity of    OSHA, 1981
    collected by             HPLC                    210 nm         assuming 24 litre        the analytical
    drawing a known                                                 sample volume, this      method permits
    volume of air             column: 25 cm ×                        is equivalent to         sampling times
    through two              4.6 mm i.d.                            0.042 mg/m3              as short as
    XAD-8 sampling           stainless steel                        (0.014 ppm)              15 min. Under
    tubes connected          column packed                                                   conditions of
    in series,               with Zorbax 8 m                                                 this procedure,
    followed by              ODS-bound, spherical                                            the possibility
    desorption with          silica particles                                                of interference
    methanol/water                                                                           from acetaldehyde,
    (1:1)                     mobile phase:                                                   acetic acid,
                             96:4 (V/V)                                                      acrylamide,
                             water/acetonitrile                                              acrolein,
                             containing 0.1% by                                              acrylonitrile,
                             volume phosphoric                                               methacrylic
                             acid; flow rate:                                                acid is excluded.
                             1 ml/min; injection                                             Method recommended
                             volume: 25 litre                                                and fully validated
                             retention                                                       by OSHA for acrylic
                             time:6 min                                                      acid determinations
                                                                                             in workplace air
                                                                                                                              

    Table 2.  (contd)

                                                                                                                              

    Sampling                 Analytical methods      Detectiona     Detection limit          Comment               Reference
    methods
                                                                                                                              

    Air is pumped            HPLC equipped           Conductivity   1 mg/m3 air              The method is         Simon et
    through a florisil       with Aminex HPX         detector       (10 litre                rapid, easy and       al., 1989
    tube at a rate of        OFH organic acid                       sample volume)           appears suitable for
    1 litre/min. The         analysis column                                                 the determination
    sorbent is mixed         (300 mm × 7.8 mm).                                              of acrylic acid
    with water (5 ml)        Eluent, 2.5 × 10-4                                              when present in
    and 1N H2SO4 (10 µl)     M benzoic acid                                                  industrial emissions
    prior to injection       is pumped at                                                    containing other
    to the chromatographic   0.8 ml/min                                                      aliphatic acids
    system
                                                                                                                              

    a  FID = Flame ionisation detector
    
         Air samples are collected on silica gel treated with
     p-methoxyhydroquinone used as an inhibitor of polymerization
    (Vincent & Guient 1982) or on XAD-8 sampling tubes (OSHA, 1981). XAD-8
    sampling tubes contain solid sorbent, i.e. acrylic ester polymer, of
    16-50 mesh (OSHA, 1981).

         After separation with gas chromatographic (GC) technique or
    reverse phase high performance liquid chromatography (HPLC), flame
    ionization detection (Vincent & Guient 1982) or UV detection at 210 nm
    (OSHA, 1981) are utilized, respectively. The latter method was
    modified and recommended by OSHA as a fully validated method for the
    determination of acrylic acid in workplace air (OSHA, 1981). This
    method, when coupled with an ion suppression technique, proved
    successful for the retention and separation of acrylic acid.

         A retention time of approximately 6 min is obtained with a Dupont
    Zorbax ODS 8-µm silica packed column and a water/acetonitrile (96:4)
    mobile phase containing 0.1% (by volume) phosphoric acid. The
    phosphoric acid serves to suppress the ionization of acrylic acid
    resulting in the retention of the undissociated form of the molecule.
    Under these conditions acrylic acid is separated from potential
    interfering substances: methacrylic acid, acrylamide, acrolein,
    acrylonitrile and acetic acid. Propanoic acid, a saturated precursor
    of acrylic acid, can be resolved from acrylic acid in a 13-min
    analysis at 1 ml/min flow rate using a 0.1% aqueous phosphoric acid
    mobile phase. Detection of acrylic acid at 210 nm is approximately 100
    times more sensitive than that of propanoic acid, owing to the
    unsaturated nature of acrylic acid. This method permits the detection
    of acrylic acid in the presence of very high levels of propanoic acid.

         A third method utilizes high-performance ion-exclusion
    chromatography with conductimetric detection (Simon et al., 1989). The
    use of 2.5 × 10-4 M benzoic acid as the mobile phase in this method
    allows the separation of acrylic acid from propionic acid and other
    aliphatic acids.

    2.4.2  In industrial effluents

         A gas chromatographic method has been developed for the analysis
    of acrylic acid and some other related pollutants present in small
    quantities in the effluent from a methyl acrylate plant in India
    (Singh & Thomas, 1985). In this method, effluent samples were injected
    directly to the GC system without prior extraction or concentration. A
    Porapak Q (4 feet × 1/8 inch I.D.) column and a FID were utilized in
    this method. The experimental parameters for the analysis are: column
    temperature, 165°C; injector and detector temperature, 250°C; carrier
    gas, N2 at 50 ml/min; hydrogen pressure, 1.3 kg/cm2; air pressure,
    2.2 kg/cm2 and injection volume, 1-10 µl. The method was found to be
    sensitive for detecting acrylic acid at concentrations as low as
    1 ppm.

    2.4.3  In polyacrylate materials

         A differential pulse polarographic method was used for the
    determination of residual acrylic acid in sodium polyacrylate
    polymeric systems (Husain et al., 1991). The method has the advantage
    of analysing acrylic acid in trace quantities directly without
    resorting to separation techniques. Sample solutions of the tested
    polymers were extracted with  N,N-dimethylformamide several times and
    the extraction mixture was made up to 25 ml, with the solvent
     tert-butyl ammonium iodide (0.02 M) in  N,N-dimethylformamide
    serving as the supporting electrolyte. The polarographic measurements
    were performed with a Metrohm E-506 Polarecord equipped with a three-
    electrode system (a dropping mercury electrode (DME), Ag/AgCl
    (saturated KCl) reference electrode, and an auxiliary platinum
    electrode). Using this method, free acrylic acid in polymers at levels
    of 10-100 ppm can be measured with a precision of ± 3%.

    2.4.4  In biological samples

         Methods for the analysis of acrylic acid in aqueous samples and
    tissues extracts in metabolic studies have been reported (Mao et al.,
    1994; Mitchell & Petersen, 1988; Black et al., 1995). In these
    methods, high-performance ion-exclusion chromatography and/or reverse
    phase HPLC with radiometric, refractive index, photo diode-array and
    UV detectors were used for the separation and quantification of
    acrylic acid.

         In another study, residues of acrylic acid in an anaerobic
    degradation mixture were quantified using a gas chromatographic
    technique with a flame ionization detector (FID) (Stewart et al.,
    1995). The column was an 80/120 Carbopak B-DA/4% Carbowax 20 M. The
    column and FID temperatures were 175 and 200°C, respectively. The
    carrier gas was helium at a flow rate of 24 ml/min. The detection
    limit was 1 mg/litre.

    3.  SOURCES OF HUMAN AND ENVIRONMENTAL EXPOSURE

    3.1  Natural occurrence

         Acrylic acid has been reported to occur naturally in the
    following species of marine algae: 9 species of Chlorophyceae, 10
    species of Rhodophyceae and 11 species of Phaeophyceae (Sieburth,
    1960, Glombitza, 1970a,b, 1979). It is also produced in
     Phaeodactylum  tricornutum,  Phaeocystis spp. and  Polysiphonia
    lanosa (Brown et al., 1977), as a result of hydrolysis of dimethyl-ß-
    propiothetin (Verschueren, 1983).

         Acrylic acid has been identified as an antibacterial substance in
    oysters (Brown et al., 1977), scallops, ( Patinopecten yessoensis)
    (Kodama & Ogata, 1983), and the digestive tract of penguins (Sieburth,
    1960; Herwig 1978). It is thought to originate from the phytoplankton
     Protogonyaulax (Kodama & Ogata, 1983),  Phaeocystis spp (Sieburth,
    1960) and  Phaeodactylum tricornutum (Brown et al., 1977) on which
    the molluscs and penguins fed. It has also been shown that under
    natural conditions acrylic acid is generated by certain species of
    algae and acts as a microbiocide (Glombitza, 1970a,b, 1979; Heyser &
    Glombitza, 1972). It has also been identified as the agent responsible
    for the antimicrobial activity of the marine algae  Gracilaria
     corticata and  Ulva lactuca (Bandara et al., 1988).

         Acrylic acid has been found in the rumen fluid of sheep as a
    result of bacterial fermentation of carbohydrates (Noble & Czerkawski,
    1973), where it is converted by rumen microorganisms to propionic acid
    (Whanger & Matrone, 1967). It can also be produced from lactic acid by
    the anaerobic rumen bacterium  Megasphaera elsdenii in the presence
    of 3-butynoic acid (Sanseverino et al., 1989).

         Acrylic acid has been found in agricultural rum obtained by
    fermentation of sugarcane juice by the action of  Micrococci spp
    (Ganou-Parfait et al., 1988).

    3.2  Anthropogenic sources

    3.2.1  Production levels and processes

    3.2.1.1  Manufacturing process

         The first commercial process for the manufacture of acrylic acid
    and its esters involved hydrolysis of ethylene cyanohydrin in sulfuric
    acid. This route is no longer commercially significant (Kirk-Othmer
    1984).

         Most commercial acrylic acid is now produced via a process in
    which propylene is vapour-oxidized to acrolein, which is in turn
    oxidized at 300°C with molybdenum-vanadium catalyst to acrylic acid
    (NLM, 1989). Other methods of production are as follows:

    *    a modification of the Reppe process by the reaction of acetylene,
         carbon monoxide and alcohol with a nickel catalyst;

    *    by hydrolysis of acrylonitrile;

    *    condensation of ethylene oxide with hydrocyanic acid followed by
         reaction with sulfuric acid at 160°C;

    *    a process in which formaldehyde undergoes a type of aldol
         reaction with a large molar excess of acetic acid in the vapour
         phase in a catalyst tube containing calcium Decalso (Kirk-
         Othmer, 1984);

    *    a heterolytic dehydration pathway of lactic acid in supercritical
         water (Mok et al., 1989).

    3.2.1.2  Impurities

         Commercial acrylic acid is available in two grades: technical and
    glacial. Glacial grade is 98-99.5% acrylic acid (NLM, 1989). This may
    contain, as impurities, water up to 0.3% w/w and acrylic acid dimer up
    to 0.1% w/w (BASF, 1992; Elf Atochem, 1992).

    3.2.1.3  Other sources

         Acrylic acid has also been detected in trace amounts in
    commercial propionic acid (Kostanyan et al., 1969).

    3.2.1.4  Production data

         Available data on the production of acrylic acid are shown in
    Table 3.

    Table 3.  Production data

                                                                        

    Country                  Year     Production of     Reference
                                      acrylic acid
                                      (in kilotonnes)
                                                                        

    China                    1994         105           CEFICA (1995)a

    European Community       1975         155           IARC (1979)
                             1994         665           CEFIC (1995)a

    Japan                    1976          70           IARC (1979)
                             1994         420           CEFIC (1995)a

    Korea                    1994          60           CEFIC (1995)a

    Taiwan                   1994          50           CEFIC (1995)a

    USA                      1993         332           US ITC (1983)
                             1985         361           US ITC (1985)
                             1986         348           US ITC (1986)
                             1987         499           US ITC (1987)
                             1988         480           US ITC (1988)
                             1991         554           NLM (1991)
                             1994         685           CEFIC (1995)a
                                                                        

    a    Submission of the European Council of Chemical Industry
         Federations (CEFIC) to the European Union Chemicals risk
         assessment document.

         The worldwide production of acrylic acid was approximately
    1.13 million tonnes in 1991 (Chemical Marketing Reporter, 1992).
    Worldwide capacity for acrylic acid production was reported to be
    2 million tonnes in 1994 (CEFIC, 1995).

    3.2.2  Experimental production of acrylic acid by bacterial isolates

         The following bacterial species have been utilized in
    experimental systems to produce acrylic acid:

    *    from acrylonitrile: (1) by the action of epsilon-caprolactum-
         induced  Rhodococcus rhodochrous J1 (Nagasawa et al., 1990);
         with a periodic substrate feeding system the highest accumulation
         (390 g/litre) was obtained; (2) by  Arthrobacter sp. isolated
         from petrochemical industry waste (Narayanasamy et al., 1990).

    *    from acrylamide by the action of  Pseudomonas sp. and
          Xanthomonas maltophilia isolated from herbicide-contaminated
         soils (Nawaz et al., 1993, 1994); batch culture of these bacteria
         completely degraded 62.8 mM acrylamide to acrylic acid and
         ammonia in 24 and 48 h, respectively.

    3.2.3  Uses

         Acrylic acid is used primarily: as a starting chemical for ethyl
    acrylate,  n-butyl acrylate, methyl acrylate, 2-ethylhexyl acrylate;
    as a monomer for polyacrylic acid and salts, cross-linked high (and
    low) molecular weight polymers; as a co-monomer with acrylamide for
    polymers used as flocculants; with ethylene for ion-exchange resin
    polymers; with methyl ester for polymers; and with methylene succinic
    acid (itaconic acid) for other co-polymers (SRI, 1981; NLM, 1989).

         In 1987, 25% of the acrylic acid produced in the USA was used for
    surface coatings; 20% for polyacrylic acid and salts, including super-
    absorbent polymers, detergents, water treatment and dispersants; 13%
    for textiles and non-wovens; and 9% for adhesives and sealants
    (Kavaler, 1987).

         Until 1979, in the European Union countries more than 80% of
    acrylic acid was used for the production of polyacrylates and in Japan
    90% was used in the production of acrylic esters (IARC, 1979). In
    1988, European use of acrylic acid was 69% for esters, 10% for
    detergents, 8.5% for flocculants and dispersants and 6.5% for super-
    absorbers (CEFIC, 1995).a

              

    a    Submission of the European Council of Chemical Industry
         Federations (CEFIC) to the European Union chemicals risk
         assessment document.

         Other uses are in the production of copolymers for dental
    adhesives (Bowen, 1979), in the production of hydrogels used for
    contact lenses (Kirk-Othmer, 1984), in surface coating formulations
    (Kirk-Othmer, 1984), and in latex applications to increase stability
    in order to prevent premature coagulation (Kirk-Othmer, 1984).

    4.  ENVIRONMENTAL TRANSPORT, DISTRIBUTION AND TRANSFORMATION

    4.1  Transport and distribution between media

         Acrylic acid is miscible with water (Riddick et al., 1986) and
    therefore would not be expected to adsorb significantly to soil or
    sediment (Lyman et al., 1982). The Henry's Law constant for acrylic
    acid is reported to be 3.2 × 10-7 atm m3/mol (Singh et al., 1984).
    Under soil conditions, chemicals with such low Henry's Law constants
    are essentially non-volatile (Lyman et al., 1982). However, the vapour
    pressure of acrylic acid suggests that it volatilizes from surface and
    dry soil (Howard, 1991).

         The adsorption and desorption of acrylic acid were examined in
    five different soils: an aquatic sandy loam sediment, a loamy sand, a
    clay loam and two loams. The average Koc for the adsorption of
    acrylic acid to soil was 43, and ranged from 23 to 63. The Koc values
    for the desorption data were widely scattered with values ranging from
    18 to 837. This indicates that the degree of adsorption is not
    correlated to the organic carbon content (OC), which ranged from 0.46%
    for the loamy sand to 4.58% for one of the loams. The results of this
    study indicate a high mobility of acrylic acid through soil (Archer &
    Horvath, 1991).

         Using the fugacity model of Mackay & Peterson (1981) the
    theoretical distribution of acrylic acid has been estimated. About 97%
    of acrylic acid released to the environment should be associated with
    the aquatic environment (the water phase), approximately 1.6% in air,
    1% in sediment and < 1% in soils, suspended solids and biota
    (Staples, 1993).

         Since the atmospheric lifetime of acrylic acid is less than one
    month (Atkinson, 1987), there is no potential for long-range transport
    of this compound.

    4.2  Transformation

    4.2.1  Abiotic degradation

         The UV absorption band of acrylic acid extends to about 320 nm
    (Weast & Astle, 1985). Vapour phase acrylic acid reacts with
    photochemically produced hydroxyl radicals primarily by addition to
    the double bond and with atmospheric ozone, resulting in an estimated
    overall half-life of 6.6 h to 6.5 days (Atkinson & Carter, 1984).
    Based upon the estimated rate constant for vapour phase reactions and
    assuming hydroxyl radical concentrations of 5 × 105 radicals per cm3
    and an ozone concentrations of 7 × 1011 molecules per cm3 (Atkinson
    and Carter, 1984; Atkinson, 1987), a half-life of 2.5-23.8 h was
    estimated by Howard et al. (1991).

         Acrylic acid was found to be stable to hydrolysis at pH values
    between 3.7 and 11 (Shah, 1990).

    4.2.2  Biodegradation

    4.2.2.1  Aerobic biodegradation

         When added to water, acrylic acid is rapidly oxidized, and
    wastewater containing the compound can deplete reservoirs of oxygen
    (Ekhina & Ampleeva, 1977).

         Several biodegradability studies show that acrylic acid will
    readily biodegrade (Lyman et al., 1982; Keystone Environmental
    Resources, 1989a; Douglas & Bell, 1992). The BOD5 (biological
    oxygen demand, 5 days) for glacial acrylic acid, using acclimated,
    fresh dilution water and raw sewage from a local treatment plant as
    the inoculum, was determined to be 0.315 g of oxygen consumed per gram
    of product. The COD (chemical oxygen demand) under the same conditions
    was 1.48 g/g (Keystone Environmental Resources, 1989)a; therefore,
    the BOD5/COD ratio was 0.21. A BOD5/COD ratio of 0.26 was also
    reported by Lyman et al. (1982). Biodegradation of acrylic acid in a
    14-day BOD test was up to 68% (CITI, 1992). Acrylic acid at a
    concentration of 3 mg/litre attained 81% biodegradation within 28 days
    in a closed-bottle test based on the consumption of oxygen (Douglas &
    Bell, 1992). The pass level of 60% was reached within 10 days of
    exceeding the 10% level, and so acrylic acid is considered to be
    "readily biodegradable" according to EC classification criteria (EEC,
    1988).

         The metabolism of 14C-acrylic acid in sandy loam soil has been
    studied under aerobic conditions for up to 28 days after treatment at
    a rate of 100 mg/kg. Acrylic acid was rapidly metabolized; after 3
    days no acrylic acid was detected in soil extracts. Carbon dioxide
    evolution accounted for 72.9% of applied radioactivity by day 3 and a
    total of 81.1% over the 28-day study period. The half-life for acrylic
    acid under these conditions was estimated to be less than 1 day
    (Hawkins et al., 1992).

         Acrylic acid formed from hydrolysis of acrylamide added to soil
    was totally degraded within 15 days of its formation (Nishikawa et
    al., 1979). In a 42-day screening study using a sewage seed inoculum,
    71% of acrylic acid was mineralized under aerobic conditions. After
    previous acclimatization, 81% of acrylic acid degraded to carbon
    dioxide in 22 days (Pahren & Bloodgood 1961; Chou et al., 1978).

              

    a    Report sent by J.M. Flaherty to J. McLanghlin, Rohm and Haas
         Spring House (work order numbers M8903002 and M8902005).

         A collection of strains utilizing acrylonitrile, acrylamide and
    acrylic acid as sole carbon and/or nitrogen source was isolated from
    environmental samples. Strains with maximum decomposing activity were
    identified as  Pseudomonas pseudoalcaligenes 6p;  P.alkaligenes 5g
    and  Brevibacterium spp. 13 PA (Moiseeva et al., 1991).

         An aerobic gram-negative bacterium ( Pseudomonas sp.) isolated
    from tropical garden soil was found to be able to degrade a high
    concentration of acrylamide (4 mg/litre) to acrylic acid and ammonia,
    which were utilized as sole carbon and nitrogen sources, respectively,
    for growth (Shanker et al., 1990).

         A strain of  Byssochlamys sp. produced ß-hydroxypropionic acid
    (ß-HPA) when grown on media containing high concentrations of acrylic
    acid. The maximal production of ß-HPA was 4.8% when the initial
    culture medium contained 7% acrylic acid and 2% glucose and the
    initial culture pH was adjusted to 7.0 (Takamizawa et al., 1993).

         Acrylic acid has been reported to be significantly degraded
    (> 30%) in the MITI test, a biodegradability screening test of the
    Japanese Ministry of International Trade and Industry (Sasaki, 1978).
    Acrylic acid was completely degraded in a standard Zahn-Wellens test
    and the authors concluded that it is biodegradable (BASF, 1993).

         Acrylic acid has been found to be degraded by a strain of
     Alcaligenes denitrificans isolated from a landfill soil. The
    bacterium degraded acrylic acid through the intermediate formation of
    L-(+)-lactic and acetic acids, which were further metabolized
    (Andreoni et al., 1990).

    4.2.2.2  Anaerobic biodegradation

         Speece (1983) reported that acrylic acid can undergo ultimate
    anaerobic biodegradation. In an anaerobic screening study utilizing
    10% sludge from a secondary digester as an inoculum, acrylic acid was
    judged to be degradable, with over 75% of theoretical methane being
    produced within 8 weeks of incubation (Shelton & Tiedje, 1984).

         In another study, acrylic acid was toxic to unacclimated
    anaerobic acetate-enriched cultures and was poorly utilized (21%) in a
    completely mixed anaerobic reactor with a 20-day hydraulic retention
    time after a 90-day acclimatization period (Chou et al., 1978). A
    possible explanation for the conflicting results of anaerobic
    degradation is the observation that acetate cultures have to exhaust
    the acetic acid as carbon and energy source before they can utilize a
    cross-fed compound (Chou et al., 1978).

         The biodegradability of acrylic acid using methanogenic acetate
    enrichment culture was studied by Stewart et al. (1995). Acrylic acid
    was degraded with almost no effect on methanogens with spikes up to
    100 mg/litre. However, concentrations of 500, 1000 and 1500 mg/litre
    were found to inhibit the methanogens for several days before

    recovery. Acrylic acid was eventually degraded to less than 1 mg/litre
    (> 99% of initial concentration) in all cases by the end of the
    study (55 days).

    4.2.3  Bioaccumulation and biomagnification

         From the low value for log Kow, ranging from 0.161 to 0.46
    (Hansch & Leo, 1987; BASF, 1988), one would expect the
    bioconcentration of acrylic acid in organisms to be negligible Bysshe
    (1990) using a regression equation calculated theoretical
    bioconcentration factors ranging from 0.78 to 1.3. Veith et al. (1979)
    estimated the bioconcentration factor to be in the range of 1.6 to
    2.4.

         There have been no reports of biomagnification of acrylic acid in
    the food chain.

    5.  ENVIRONMENTAL LEVELS AND HUMAN EXPOSURE

    5.1  Environmental levels

         No quantitative data are available for environmental levels of
    acrylic acid in ambient air, water or soil. Acrylic acid has been
    found to occur naturally in some marine algae (Sieburth, 1960; Brown
    et al., 1977) and some molluscs (Kodama & Ogata, 1983). The acrylic
    acid content of  Phaeocystis spp. can be 7.4% of dry weight
    (Sieburth, 1960). Other marine algae have been found to contain
    acrylic acid:  Chlorophyceae, 0.124-16.5 mg/g dry weight;
     Rhodophyceae, 0-0.131 mg/kg dry weight; and  Phaeophyceae 0-0.02 mg/g
    dry weight (Glombitza, 1970a, 1979).

    5.2  General population exposure

         No data are available for general population exposure. However,
    consumers may be exposed to unreacted acrylic acid in the following
    household goods: polishes, paints and coatings, adhesives, rug
    backing, plastics, textiles and paper finishes (USEPA, 1981).
    Information on the typical content of unreacted acrylic acid in these
    kinds of products is unavailable.

         Populations living in the vicinity of plants producing acrylic
    acid or manufacturing its esters or polymers may be exposed to acrylic
    acid in the ambient air. The concentrations of emitted vapours of
    acrylic acid in the plume from such plants were found to vary from 22
    to 183 mg/m3 (Grudzinski, 1988). However, there are no data on
    concentrations of acrylic acid in the ambient air of populated areas.

         Acrylic acid occurs in wastewater effluents from its production
    by the oxidation of propylene at concentrations not exceeding
    0.5 mg/litre (Wise & Fahrentholdt, 1981). After treatment of
    wastewater from a production facility in Europe, acrylic acid levels
    were below the limit of detection (0.1 mg/litre) (CEFIC, 1995)a.
    However, effluent from a methyl acrylate plant in India was found to
    contain 2500 mg/litre as acrylic acid (Singh & Thomas, 1985).

              

    a    Submission of the European Council of Chemical Industry
         Federations (CEFIC) to the European Union chemicals risk
         assessment document.

         Since there is evidence that acrylic acid esters are hydrolysed
    to acrylic acid in laboratory animals (Ghanayen et al., 1987) and in
    human tissues  in vitro (Wiegand, 1990), a potential source of
    internal exposure to acrylic acid may result from metabolism of
    absorbed acrylic acid esters (Frederick et al., 1994; Sanders et al.,
    1988).

    5.3  Occupational exposure during manufacture, formulation or use

         Occupational exposure is the most important means of human
    exposure to acrylic acid. Inhalation and contact with skin are
    important routes of exposure.

         The National Institute of Occupational Safety and Health (NIOSH)
    conducted two observational nationwide surveys, a decade apart, to
    determine the extent of exposure of workers to a variety of substances
    in their work environment. The National Occupational Hazard Survey
    (NOHS) was conducted during 1972-1974 using a stratified probability
    sample of 4636 businesses in 67 metropolitan areas throughout the USA
    employing nearly 900 000 workers (NIOSH 1974, 1977). According to the
    NOHS, an estimated 28 600 workers were potentially exposed to acrylic
    acid, approximately 10% of whom were exposed to acrylic acid and 90%
    to trade-name products. However, this estimation excluded the exposure
    of the general population to trade-name chemicals possibly containing
    acrylic acid. Acrylic acid was seen in 16 major industry groups and in
    41 occupational groups in the NOHS.

         During 1981-1983 NIOSH conducted the National Occupational
    Exposure Survey (NOES), using a stratified probability sample of 4490
    businesses in 98 different geographic locations of the USA employing
    nearly 1.8 million workers (NIOSH, 1990). According to the NOES, an
    estimated 96 500 workers were potentially exposed to acrylic acid,
    approximately 10% of whom were exposed to acrylic acid and 90% to
    trade-name products. Acrylic acid was seen in 25 major industry groups
    and in 67 occupational groups (NIOSH, 1990).

         One study conducted at a large manufacturing facility of the Rohm
    and Haas Company in the USA, where several chemicals including acrylic
    acid and a variety of acrylates and methacrylates were used, indicated
    that ethyl acrylate and acrylic acid levels varied from 0.01 to
    56 ppm. Most areas of the plant had levels (as 8-h time-weighted
    averages) well below the hygiene standards recommended at that time by
    the OSHA and the ACGIH of 10 ppm for acrylic acid and 5 ppm for ethyl
    acrylate (ACGIH, 1988, OSHA, 1989). Many of the available industrial
    hygiene data were specific for high, short-term exposure tasks
    (5-40 min samples) when chemicals were pumped into containers for
    shipping or when lines were open for new connections, or to obtain
    samples. They revealed levels at the high end of the above-mentioned
    range (Schwartz et al., 1989).

         Exposures of workers to acrylic acid for short periods of time of
    less than 15 min and for full shift expressed as time-weighted average
    (TWA) concentration have been compiled from four producing companies.
    Operators had a mean short-term exposure limit (STEL) value of
    8.4 mg/m3 (range < 0.3 to 189 mg/m3); loading/unloading operations
    a mean of 3.9 mg/m3 (range 1.2 to 12 mg/m3); and those engaged in
    quality assurance a mean of 0.3 mg/m3 (range of less than 0.3 to
    0.6 mg/m3). Concerning the 8-h TWA, the operators showed levels of
    0.48 mg/m3 (range of 0.03 to 3 mg/m3) and loading/unloading
    operations a mean of 0.39 mg/m3 (range of 0.27 to 1.98 mg/m3)
    (Casciery & Clary, 1993).

         No such data are available from other countries.

    6.  KINETICS AND METABOLISM

    6.1  Human studies

         Apart from  in vitro skin absorption studies, no data are
    available on kinetics, metabolism or elimination or acrylic acid in
    humans.

         The absorption of 14C-acrylic acid (site of label unspecified)
    dissolved in acetone, water or phosphate buffer (pH 6.5) was tested
    using samples of excised (postmortem) human and mouse skin  in vitro
    (Corrigan & Scott, 1988). Acrylic acid concentrations of 0.01, 0.1,
    1.0 and 4.0% were applied at 100 µl/cm2 under occlusive conditions.
    Samples were taken from the receptor fluid up to 32 h. Rates of
    absorption decreased in the order of magnitude as follows: acetone >
    water > phosphate buffer. Independent of the vehicle, the absorption
    rate increased as a function of acrylic acid concentration.
    Permeability coefficients, which ideally are concentration-independent
    expressions of absorption rate, for human skin ranged from 0.37 to
    0.72 × 10-3 cm/h for water and from 0.47 to 1.81 × 10-4 cm/h for
    phosphate buffer. Permeability coefficients were not calculated for
    acetone because of evaporation of this volatile vehicle during the
    course of the experiments (Corrigan & Scott, 1988).

         A briefly reported  in vitro percutaneous penetration study
    using excised human cadaver skin indicated that 14C-acrylic acid
    absorption can vary significantly as a function of pH and delivery
    vehicle.  In vitro flux, estimated after a 1 mg dose was applied,
    varied by 600 times within the treatments studied and decreased in the
    order: acetone (600 µg/cm2 per h) > phosphate buffer pH 6.0 
    (23 µg/cm2 per h) > ethylene glycol (15 µg/cm2 per h) > phosphate
    buffer pH 7.4 (1 µg/cm2 per h) (D'Souza and Francis, 1988).

    6.2  Studies on experimental animals

    6.2.1.  Absorption, distribution and excretion

    6.2.1.1  Oral exposure

         After oral gavage administration of an aqueous solution of
    (1-11C)-acrylic acid (26 µg/kg body weight) to female Sprague-Dawley
    rats, it was rapidly absorbed and expired mainly as 11CO2 within 1 h
    post-administration. The uptake appeared biphasic. The short alpha-
    phase had an apparent first-order absorption constant (Ka) of 19% of
    the available dose per minute (biological half-time = 3.6 min) and the
    Ka of the ß-phase was 30% (biological half-time = 23 min). Relative
    retention of radiolabel (dpm per g tissue versus dpm per g body
    weight) after 65 min was above unity in liver (2.6), adipose tissue
    (1.9), small intestine (1.5), kidneys (1.2) and spleen (1.0).
    Approximately 6% of the radiolabel was excreted in the urine within 
    65 min (Kutzman et al., 1982).

         In another study, single gavage doses of 4, 40 or 400 mg/kg body
    weight of (2,3-14C)-acrylic acid in 0.5% aqueous methylcellulose
    solution were administered to male Sprague-Dawley rats. Approximately
    35, 55 and 60%, respectively, of the administrated dose were
    eliminated, mostly as 14CO2, within 8 h. By 24 h 50-65% of the dosed
    radioactivity was eliminated and the excretion of radioactivity had
    virtually ceased. After 72 h, 44-65% of the administrated
    radioactivity had been eliminated as 14CO2; 2.9-4.3% in urine, 2.4-
    3.6% in the faeces and 18.9-24.6% remained in the tissues examined
    (liver, stomach, muscle, blood, plasma, adipose tissue). The residual
    radioactivity was highest in the adipose tissue (9-15%), followed by
    muscle (6.5-7.5%) and liver (1.7-2.2%) (De Bethizy et al., 1987).

         The disposition of (1-14C)-acrylic acid was also determined in
    male Sprague-Dawley rats following oral administration by gavage in
    water at 400 mg/kg body weight. Excretion of acrylic acid-derived
    radioactivity was determined by collection of urine, faeces and
    expired air for 72 h following administration. The predominant route
    of excretion was in the expired air with approximately 80% of the
    radioactivity exhaled as 14CO2 within 24 h and 83.2% after 72 h.
    Elimination of radioactivity as exhaled volatile organic compounds was
    negligible (less than 0.5% of the radiolabel). Within 24 h of dose
    administration, excretion of radioactivity accounted for 5.0% in the
    urine and 8.8% of the radiolabel in faeces. Tissue concentrations of
    radioactivity after 72 h were generally low: 0.4% of the total dose in
    the liver, 0.39% in muscle and 0.18% in skin (Winter & Sipes, 1993).

         A comparative bioavailability and disposition study in male
    Fischer-344 rats and male C3H mice after a single administration of
    (1-14C)-acrylic acid (40 or 150 mg/kg body weight in water) by gavage
    has been conducted. This study confirmed that acrylic acid is rapidly
    absorbed and metabolized. In rats and mice about 80-90% of the dose
    was exhaled as 14CO2 within 24 h (Black et al., 1995). In rats,
    excretion of radiolabel in urine and faeces within 72 h accounted for
    < 5% and < 1% of the dose, respectively. Elimination of
    radioactivity in rats as exhaled organic volatile compounds was less
    than 0.5% of the radiolabel. Similar patterns were observed in male
    mice (Black et al., 1995).

    6.2.1.2  Inhalation exposure

         A tissue distribution study has been conducted in 39 female
    Sprague-Dawley rats nose-exposed to (1-11C)-acrylic acid vapour for 
    1 min (concentration not indicated). Radioactivity was widely
    distributed; 90 seconds after exposure 18.3% of the delivered dose
    remained in the rats. Approximately 28.0% of this radioactivity was
    associated with the snout and 42.9% of the radioactivity was found in
    the head; this was considered to be solubilized in the mucous of the
    turbinates and the nasopharynx. After 65 min, the activity in the
    snout was reduced to 8.1% and approximately 60% of the label was
    expired as 11CO2. The elimination of labelled CO2 appeared to be

    biphasic, with a half-time of approximately 30.6 min during the
    alpha-phase. The amount of radioactivity retained in liver and fat
    increased markedly between 1.5 and 65 min post-exposure (Kutzman et
    al., 1982).

    6.2.1.3  Dermal exposure

         In one  in vitro experiment, the dermal penetration capacity of
    (1-14C)-acrylic acid was tested using excised mouse skin. Skin slices
    were treated in a diffusion chamber with 0.01, 0.1, 1 and 4% (w/v)
    100 µl/cm2 of acrylic acid dissolved in acetone, water or phosphate
    buffer pH 6.5. The results were comparable with the study performed on
    excised human skin (section 6.1). Permeability coefficients for mouse
    skin were 0.96-1.73 × 10-3 cm/h for water and 1.91-3.1 × 10-4 cm/h
    for phosphate buffer. The permeability coefficients and steady-state
    absorption rate data indicate that mouse skin is approximately three
    times more permeable than human skin to acrylic acid (Corrigan &
    Scott, 1988). This difference may not be biologically significant.

         In a briefly reported study, male Sprague-Dawley rats were
    administered dermally 5 mg 14C-acrylic acid per kg body weight
    (D'Souza & Francis, 1988). Phosphate buffer of pH 6 or 7.4 or acetone
    was used as a formulating agent. In each case the formulation was
    applied to the shaved back of the rats and covered with a glass
    chamber. The rate of appearance of 14CO2 measured at 0.5, 1, 2, 4,
    8, 16 and 24 h after application was used as a measure of the
    absorption rate of acrylic acid. The absorption rate was dependent on
    the vehicle and decreased in the following order, acetone > phosphate
    buffer of pH 6 > phosphate buffer of pH 7.4. Cumulative absorption
    after 24 h was 22% from acetone, approximately 19% from phosphate
    buffer of pH 6, and 9% from phosphate buffer of pH 7.4. The results of
    the  in vivo investigations were comparable to those of the  in
    vitro studies obtained by the same authors (D'Souza & Francis, 1988).

         The disposition of (1-14C)-acrylic acid was determined in male
    Sprague-Dawley rats after topical application of 100 µl of a 4% (v/v)
    solution of acrylic acid in acetone to an area of 8.4 cm2 of the skin
    (501 µg/cm2) using a skin-mounted, charcoal-containing trap covered
    with fixed aluminium discs to ensure complete recovery of the label.
    Excretion of acrylic-acid-derived radioactivity was determined by
    collection of urine, faeces and expired air for 72 h following
    administration of acrylic acid. Approximately 73% of the radioactivity
    volatilized from the skin and was trapped in the charcoal sorbent.
    After 72 h, 6% of radioactivity was detected at the site of
    application in the skin or on the skin surface. Approximately 75% of
    the absorbed dose, representing about 16% of the applied dose, was
    exhaled as 14CO2 within 12 h. Excretion of radioactivity in the
    urine accounted for approximately 9% of the applied radioactivity
    (approximately 4% of the absorbed dose), the faeces containing only
    negligible amounts of radioactivity. After 72 h, less than 0.4% of the
    applied dose was retained in tissues other than skin (Winter & Sipes,
    1993).

         In another study, 1% (v/v) acetone solutions of 14C-acrylic acid
    at doses of 10 or 40 mg/kg were applied to the clipped skin of the
    shoulder region of male F-344 rats or male C3H/HeN Crl BR mice. A non-
    occlusive "frame" device was cemented to the skin surface of animals
    to allow for free evaporation of acrylic acid, which was trapped using
    on-line volatile organic traps. Since this technique was inefficient,
    activated-charcoal-impregnated filter paper sheets were placed
    occlusively on the treated skin surface of a second high dose group of
    animals to provide for absorption of evaporating acrylic acid (Black
    et al., 1995). In rats, the reported 72-h recovery was low and ranged
    from 50 to 60% of the applied dose. Evaporation accounted for most of
    the applied acrylic acid, but approximately 26 and 19% of the applied
    high and low doses were absorbed in rats within 72 h, respectively.
    The major route of elimination of absorbed acrylic acid was via
    exhalation of 14CO2 and accounted for 69.5 and 77% of the absorbed
    low and high doses, respectively. Minimal faecal elimination of
    absorbed acrylic-acid-derived radioactivity was reported (< 1%), and
    tissues and carcasses contained approximately 2-3% of the absorbed
    chemical at 72 h.

         In mice, the 72-h recovery ranged from 61.5 to 84.0% of the
    applied acrylic acid dose. As in the rat experiments, while most of
    the applied acrylic acid was lost to evaporation, absorption accounted
    for 11-12% of the applied dose. Exhalation of 14CO2 accounted for
    83.5 and 77.7% of the absorbed high and low doses, respectively.
    Elimination via other routes was negligible, and less than 1% of the
    absorbed dose remained in the tissues and carcasses at 72 h (Black et
    al., 1995).

    6.2.1.4  Intravenous administration

         Single i.v. doses of (1-14C)-labelled acrylic acid (10 mg/kg
    body weight in phosphate-buffered saline) were given to male F-344
    rats and male C3H/HeNCrlBR mice into the tail veins. In rats 63% of
    the 14C-dose was eliminated as 14CO2 after 4 h and 68% after 72 h,
    while almost no 14C was recovered as exhaled organic volatiles.
    Tissue samples (liver, kidney and fat) and plasma contained 1.9% at 1
    h, 0.4% at 8 h, and 0.2% at 72 h of the recovered dose. Overall the
    recovery was 72.8 ± 10.8%. In mice, 51% of the radioactivity was
    exhaled as 14CO2 over the 72-h collection period, the majority
    exhaled in the first 4 h. The volatile radioactive fractions were
    about 0.6% of the total dose. Overall, 55.7 ± 6.6% of this intravenous
    10 mg/kg dose was recovered in mice (Frantz & Beskitt, 1993).

    6.2.2  Metabolism

    6.2.2.1   In vitro investigations

         Oxidation of (2,3-14C)-acrylic acid was studied by incubating
    acrylic acid with hepatic microsomal preparations obtained from male
    Sprague-Dawley rats. No metabolites were detected by HPLC and acrylic
    acid was recovered unchanged from the incubation mixture (De Bethizy
    et al., 1987).

         Results of the  in vitro metabolism of (1-14C)-acrylic acid
    incubated with freshly isolated hepatocytes and liver homogenates of
    male F-344 rats or mitochondria isolated from liver homogenates of
    male F-344 rats indicate that acrylic acid is rapidly metabolized to
    14CO2. Addition of equimolar amounts of propionic acid, 3-hydroxy-
    propionic acid or 3-mercaptopropionic acid caused a significant
    inhibition of the oxidation of acrylic acid by isolated mitochondria.
    A single major metabolite co-eluting with 3-hydroxypropionic acid was
    found by HPLC analysis in the mitochondrial incubation mixtures. The
    authors suggested that acrylic acid is metabolized  in vitro by
    mammalian enzymes to CO2 via 3-hydroxypropionate by the non-vitamin-
    B12 - dependent pathway for propionate metabolism (Finch & Frederick,
    1992).

         The oxidation rate of acrylic acid in 13 different tissues
    (liver, kidney, forestomach, glandular stomach, small and large
    intestine, spleen, brain, heart, lung, skeletal muscle, fat and skin)
    of male and female C3H/HeNCrlBR mice was measured by incubating tissue
    slices with (1-14C)-acrylic acid and collecting 14CO2. All the
    tissues studied oxidized acrylic acid to a certain extent, but
    activity in kidney, followed by liver, was much higher than in other
    tissues. Oxidation of acrylic acid followed pseudo-Michaelis-Menten
    kinetics in the liver, kidney and skin, with a Km for all these
    tissues of approximately 0.67 mM. Marked differences were observed in
    the Vmax values, 2890 ± 436 nmol/h per g for kidney, 616 ± 62 nmol/h
    per g for liver and 47.9 ± 5.8 nmol/h per g for skin. Half-lives in
    these tissues were 0.13, 0.867 and 10.2 h, respectively. Lung,
    glandular stomach, heart, spleen, fat and large intestine preparations
    oxidized acrylic acid at rates from 10 to 40% of the rate determined
    in the liver; in the remaining tissues reaction rates were less than
    10% of those in the liver. Rates of metabolism in tissues from male
    and female mice were similar.3-Hydroxypropionic acid was the only
    metabolite detected by HPLC analysis following incubation of tissues
    with (1-14C)-acrylic acid. To determine if CO2 was formed from the
    C1 carbon, and if acetyl-CoA was derived from carbons 2 and 3 of
    acrylic acid, the authors incubated (2,3-14C)-acrylic acid and
    (1-14C)-acetate with liver and kidney slices and measured the rate of
    14CO2 formation. It was concluded that CO2 originated from C1, but
    that acetyl-CoA was derived from carbons 2 and 3 of acrylic acid. Both
    substrates were oxidized well by the tissues, thus providing for the
    complete metabolism of acrylic acid to CO2. The results demonstrate
    that the rate of acrylic acid metabolism varies significantly among
    mouse tissues and suggested that the kidneys and liver are major sites
    of acrylic acid metabolism (Black et al., 1993).

    6.2.2.2  In vivo investigations

         After oral administration of (2,3-14C)-acrylic acid (4, 40 or
    400 mg/kg body weight in 0.5% methylcellulose) to male Sprague-Dawley
    rats, the major portion of the radioactivity (up to 65%) was exhaled
    as 14CO2 within 24 h. In urine four metabolites were identified by
    HPLC analysis. One of the two major metabolites eluted very near to

    the solvent front and did not co-elute with acetic acid pyruvic acid
    or lactic acid. The second metabolite co-eluted with 3-hydroxypro-
    pionic acid. Traces of two other unidentified residues were also
    detected. Radioactivity could not be detected at the retention times
    corresponding to that of 2,3-epoxypropionic acid, glyceric acid or
     N-acetyl- S-(2-carboxy-2-hydroxyethyl)-cysteine, suggesting that
    acrylic acid is not epoxidized to 2,3-epoxypropionic acid  in vivo.
    It was suggested that acrylic acid was metabolized by the non-vitamin-
    B12-dependent pathway for propionic acid metabolism, with degradation
    to CO2 being the main route of elimination. Residual radioactivity in
    tissues may be due to incorporation of 14C from acrylic acid into
    acetyl-CoA (De Bethizy et al., 1987).

         Using HPLC and NMR analysis, 3-hydroxypropionic acid,  N-acetyl-
     S-2-(2-carboxyethyl)-cysteine and  N-acetyl- S-(2-carboxyethyl)-
    cysteine-S-oxide were identified as urinary metabolites after oral
    administration of (2,3-14C)-acrylic acid (400 mg/kg body weight in
    water by gavage) to male Sprague-Dawley rats. According to the
    authors, the detection of mercapturates may be a consequence of the
    high dose used in this study (Winter et al., 1992).

         HPLC analysis for acrylic acid and its metabolites in rats
    revealed that a metabolite that coeluted with 3-hydroxypropionic acid
    was found in the urine, plasma and liver of rats that had received
    acrylic acid by gavage. Furthermore, a material that co-eluted with
    authentic acrylic acid was detected in the urine and liver, but not in
    the plasma, of these rats. Acrylic acid, but not 3-hydroxypropionic
    acid, was also detected in the urine of rats after cutaneous
    application (Black et al., 1995). In mice, 3-hydroxypropionic acid was
    identified in the liver after gavage administration of acrylic acid.
    No acrylic acid was detected in the liver of these animals (Black et
    al., 1995).

    6.2.2.3  Metabolic pathways

         Acrylic acid is rapidly metabolized to CO2, a major metabolite
    formed via acrylyl-CoA by the non-vitamin-B12-dependent pathway of
    mammalian propionate catabolism (Finch & Frederick, 1992; Winter et
    al., 1992; Black et al., 1993; Winter & Sipes, 1993). This pathway
    occurs in the mitochondrion (Finch & Frederick, 1992) and consist of
    reactions analogous to fatty acid ß-oxidation (Schultz, 1991).
    ß-oxidation is the major route of propionate catabolism in many
    invertebrates and plants (Wegner et al., 1968; Halarnkar & Blomquist,
    1989); however the primary pathway of propionate catabolism in mammals
    is that involving the vitamin-B12-dependent enzyme, methyl-malonyl-
    CoA mutase (Black et al., 1993). A small amount of 3-hydroxypropionic
    acid was identified as the major urinary metabolite of acrylic acid
    (De Bethizy et al., 1987; Winter et al., 1992). There is no evidence
    to suggest that epoxide intermediates are formed during the metabolism
    of acrylic acid (De Bethizy et al., 1987).  N-acetyl- S-(2-
    carboxyethyl) cysteine and  N-acetyl- S-(2-carboxyethyl) cysteine-
     S-oxide were identified in the urine of rats that had received

    400 mg/kg (2,3,-14C)-acrylic acid by gavage (Winter et al., 1992),
    suggesting a direct reaction between acrylic acid and reduced
    glutathione.

         The major route of metabolism for acrylic acid esters has been
    shown to involve the rapid cleavage of the ester bond by carboxyl
    esterases (see Fig. 1) (Ghanayem et al., 1987; Sanders et al., 1988;
    Frederik et al., 1994). Thus exposure to acrylic acid esters may
    constitute a significant internal exposure to acrylic acid. A
    secondary metabolic pathway involves conjugation of the acrylic acid
    ester with glutathione to yield acetyl- S-(2-carboxyethyl) cysteine
    alkylesters. (Ghanayem et al., 1987; Sanders et al., 1988). This
    intermediate may be further metabolized to  N-acetyl- S-(2-
    carboxyethyl) cysteine and  N-acetyl- S-(2-carboxyethyl)-cysteine-
     S-oxide. However, it is currently uncertain what proportion of  N-
    acetyl- S-(2-carboxyethyl) cysteine, or its oxide, formed from the
    metabolism of the acrylic acid esters originates from the reaction of
    the intact ester with glutathione and what proportion originates from
    the conjugation of the released acrylic acid with glutathione (see Fig
    1).

         On the basis of available information, proposed metabolic
    pathways for acrylic acid are summarized in Fig. 1. The proposed
    scheme also includes relationships between metabolism of acrylic acid
    and its esters (e.g., ethyl acrylate) and metabolism of propionate via
    the major vitamin-B12-dependent pathway.

    FIGURE 2

    7.  EFFECTS ON EXPERIMENTAL ANIMALS AND IN VITRO TEST SYSTEMS

    7.1  Single exposure

         The acute toxicity of acrylic acid is difficult to ascertain,
    owing to the wide range of LD50 values reported (Table 4). However
    most data indicate that the substance is of low to moderate toxicity
    by the oral and inhalation routes and of moderate toxicity by the
    dermal route. It has been proposed that the wide variation in oral
    LD50 values may be due to the different forms in which acrylic acid
    has been applied, i.e. undiluted, in aqueous solution at various
    concentrations or in neutralized solution (BG Chemie, 1991).

         Stomach lesions, necrosis and haemorrhage have been reported
    following oral dosing of rats with acrylic acid (Ghanayem et al.,
    1985; DeBethizy et al., 1987). The lowest dose at which lesions were
    seen was 144 mg/kg.

         CrL:CDBR rats were exposed (whole body) to aerosol (mean mass
    median diameter of 2.3 µm ± 2.3) concentrations of acrylic acid
    ranging from 8775 to 14 145 mg/m3 (2925 to 4715 ppm) for 30 min, 8139
    to 12 624 mg/m3 (2713 to 4208 ppm) for 60 min, and 3669 to 
    10 239 mg/m3 (1223 to 3413 ppm) for 120 min. Additionally, rats were
    exposed (whole body) to acrylic acid vapour concentrations ranging from
    2784 to 6426 mg/m3 (928 to 2142 ppm) for 60 min. Exposure to acrylic
    acid produced treatment-related signs of nasal mucosa, upper airway and
    lower airway irritation, ocular irritation, corneal opacities and
    dermal toxicity in all experimental groups. Deaths, as a function of
    both aerosol concentration and exposure duration, were seen in the
    30-, 60- and 120-min aerosol exposures. No deaths resulted from the
    vapour exposures. Following the 14-day observation period, necropsies
    revealed treatment-related alterations of the lungs, eyes and skin
    consistent with that of an irritant. However, comparison of LC values
    suggested no difference in toxicity between the aerosol and vapour
    (Hagan & Emmons, 1991).



        Table 4.  The acute toxicity (LD50 and LC50) of acrylic acid for experimental animals

                                                                                                             

    Species     Route               Parameter         Dose                Reference
                                                                                                             

    Mouse       oral                LD50              830 mg/kg           Klimkina et al., 1969

    Mouse       oral                LD50              1200 mg/kg          Zeller, 1958

    Rat         oral                LD50              193 mg/kg           IARC, 1979

    Rat         oral                LD50              340 mg/kg           Carpenter et al., 1974

    Rat         oral                LD50              1350 mg/kg          Majka et al., 1974

    Rat         oral                LD50              1500 mg/kg          Zeller, 1958

    Rat         oral                LD50              2520 mg/kg          Fassett, 1963

    Rat         oral                LD50              2100-3200 mg/kg     Miller, 1964

    Rat         oral                LD50              2500 mg/kg          Verschueren, 1983

    Mouse       subcutaneous        LD50              1590 mg/kg          Sittig, 1985

    Rabbit      percutaneous        LD50              295 mg/kg           Carpenter et al., 1974

    Rabbit      percutaneous        LD50              640 mg/kg           Gelbke & Hofman, 1979

    Rabbit      percutaneous        LD50              750 mg/kg           IARC, 1979

    Rabbit      percutaneous        LD50              950 mg/kg           Fassett, 1963

    Mouse       inhalation          LC50 (2 h)        5300 mg/m3          RTECS, 1989

    Rat         inhalation          LC50 (30 min)     26 000 mg/m3        Hagan & Emmons, 1991

                                    LC50 (60 min)     11 100 mg/m3

                                    LC50 (120 min)    7500 mg/m3
                                                                                                             

    Table 4. (contd.)

                                                                                                             

    Species     Route               Parameter         Dose                Reference
                                                                                                             

    Rat         inhalation          LC50 (4 h)        3600 mg/m3          Majka et al., 1974

    Rat         inhalation          LC50 (4 h)        > 5100 mg/m3        Klimisch & Zeller, 1980

    Mouse       intraperitoneal     LD50              17 mg/kg            Lawrence et al., 1972

    Mouse       intraperitoneal     LD50              128 mg/kg           RTECS, 1989

    Mouse       intraperitoneal     LD50              140 mg/kg           Zeller, 1958

    Rat         intraperitoneal     LD50              24 mg/kg            Majka et al., 1974

    Rat         intraperitoneal     LD50              24 mg/kg            Singh et al., 1972
                                                                                                             
    

         In a single inhalation study in rats, no deaths occurred when
    six animals were exposed to acrylic acid at a concentration of
    12 000 mg/m3 (4000 ppm) for 4 h and observed over 14 days (Union
    Carbide Corp., 1977).

         A single 4-h exposure of six rats to 6000 mg/m3 (2000 ppm) of
    acrylic acid caused no death (Carpenter et al., 1974).

         One 5-h exposure to an atmosphere saturated with acrylic acid
    (6000 ppm or 17 700 mg/m3) given to four rats (2 male, 2 female)
    produced nose and eye irritation, respiratory difficulty and
    unresponsiveness in all rats. One rat died. Histopathological
    examination showed lung haemorrhage and degenerative changes in the
    liver and kidney tubules of all rats (Gage, 1970), but these were
    possibly secondary changes in dying animals.

         Rats exposed for 1 h to acrylic acid concentrations of 300, 900
    or 1500 mg/m3 (100, 300 or 500 ppm) exhibited exposure-dependent
    decreases in both respiratory frequency and minute volume (Silver et
    al., 1981).

         In a sensory irritation study, the single exposure to acrylic
    acid vapour estimated for a 50% reduction of the respiratory rate
    (RD50) was 1539 mg/m3 (513 ppm) in F344/N rats and 2055 mg/m3
    (685 ppm) in B6C3F1 mice. During exposure to 225 mg/m3 (75 ppm) of
    acrylic acid vapour for 6 h, a 20-30% decrease in minute volume was
    observed in both species (Buckley et al., 1984).

    7.2  Irritation and sensitization

    7.2.1  Eye irritation

         Application of acrylic acid in different concentrations (glacial,
    10%, 3% and 1%) to rabbit eyes revealed that it is corrosive in high
    concentrations, i.e. glacial and 10%; 1% and 3% solution caused eye
    irritancy (Majka et al., 1974). There are also other reports of
    undiluted acrylic acid causing eye irritation and corneal damage
    (Carpenter et al. 1974; BG Chemie, 1991).

    7.2.2  Skin irritation and sensitization

    7.2.2.1  Skin irritation

         Undiluted acrylic acid is corrosive to rabbit skin (Carpenter et
    al., 1974; Majka et al., 1974; BG Chemie, 1991). A study with rabbits
    reported that a one-minute exposure to a 50% or 20% aqueous solution
    caused, respectively, erythema and oedema or slight erythema (BG
    Chemie, 1991). Another study reported a 10% solution to be corrosive
    when applied to rabbit skin and that a 0.6-5% solution caused
    irritation of various severity (Majka et al., 1974).

         The irritant effects of repeated dermal exposure have also been
    investigated. A 5% acrylic acid solution in acetone caused skin
    irritation in the mouse after daily non-occlusive application for 14
    days (DePass et al., 1984). No irritation was seen with a 1% solution.
    In another study, groups of three strains of mice received dermal
    applications of 0.1 ml acrylic acid in acetone 3 times a week for 13
    weeks at concentrations of 0, 1 or 4% (Tegeris et al., 1987, 1988). At
    4%, there were signs of significant skin irritation (desquamation,
    fissures and eschar), with proliferative, degenerative and
    inflammatory changes being detected histologically in the epidermis
    and dermis, from weeks 1 to 2. At 1%, minimal proliferative changes,
    detected histologically, were the only effects seen. No differences
    were found between the response of the three strains of mice.

    7.2.2.2  Skin sensitization

         Acrylic acid has been tested for contact sensitivity in guinea-
    pigs. In one study, a 20% aqueous solution of pure unstabilized
    acrylic acid was applied to the skin once a day until definite skin
    irritation was seen. When challenged topically 11 days later with a 2%
    solution, there was no evidence of skin sensitization up to 24 h post-
    challenge (BG Chemie, 1991).

         In another study, the highest non-irritating concentration of
    acrylic acid (not specified) was applied topically four times in 10
    days. At the time of the third application, Freund's adjuvant was
    injected intradermally. When challenged two weeks later, none of the
    10 guinea-pigs showed evidence of skin sensitization (Rao et al.,
    1981).

         Three out of six guinea-pigs exposed to acrylic acid, said to be
    99% pure, showed a skin sensitization response in a Polak test (Parker
    & Turk, 1983). Induction was by dermal injections of a total of 1 mg
    acrylic acid, together with adjuvant, followed by topical challenge
    with 5% acrylic acid. However, the impurities and inhibitors of the
    acrylic acid used were not mentioned in the report.

         Acrylic acid was found to be an extreme sensitizer by the guinea
    pig maximization test and a weak sensitizer by the Landsteiner Draize
    test. The compound used for testing was considered pure, but no
    analytical data were provided (Magnusson & Kligman, 1969).

         Acrylic acid gave a clearly positive result in the Freunds
    Complete Adjuvant test in guinea-pigs (Waegemaekers & van der Walle,
    1984). Induction was by three intradermal injections of 1.2% followed
    by topical application of 2.2 or 7.2%. The positive response was
    believed to be due to the historical impurity, alpha,ß-
    diacryloxypropionic acid. This impurity was identified in acrylic acid
    from just one of three suppliers. Limited testing of acrylic acid from
    the other two suppliers gave negative skin sensitization results. It
    should be noted that the impurity is not present in acrylic acid
    resulting from current production methods involving distillation.

         Commercial acrylic acid also contains a small amount of
    polymerization inhibitors, usually hydroquinone monomethyl ether
    (methoxyphenol). This is a known skin sensitizer in guinea-pigs (van
    der Walle et al., 1982). Other inhibitors used with acrylic acid have
    also been reported to have skin-sensitizing properties, namely pheno-
    thiazine (Costellati et al., 1990) and diphenyl- p-phenylenediamine
    (Magnusson et al., 1968; Kalimo et al., 1989). However, it is unclear
    whether the small amount of one of these inhibitors present
    (0.02-0.1%) could contribute to the skin-sensitizing properties of
    commercial acrylic acid.

    7.2.3  Upper respiratory tract irritation

         Olfactory cell proliferation, as measured by tritiated thymidine
    incorporation, was investigated in male F-344 rats and B6C3F1 mice
    exposed to 224 mg/m3 (75 ppm) acrylic acid 6 h daily for 5 days. A
    17-fold increase in cell proliferation occurred in mice and a 4-fold
    increase in rats (Swenberg et al, 1986). Further information on upper
    respiratory tract irritation is given in sections 7.1 and 7.3.2.

    7.3  Short-term exposure

         Results of key studies on the short-term repeated exposure
    effects of acrylic acid are presented in Table 5.



        Table 5.  Key studies on the noncarcinogenic effects of repeated exposures to acrylic acid

                                                                                                                                                

    Species, route and dosage       LOELa               NOELa              Observed effects                Reference
                                                                                                                                                

    Rat, Fisher-344 oral,           250 mg/kg bw/day    83 mg/kg bw/day    Decreased body weight,          De Pass et al.,
    drinking-water, 0, 83,                                                 reduced water and food          1983
    250, 750 mg/kg body                                                    consumption, changes in
    weight/day for 3 months                                                organ weights

    Rat, Wistar, gavage, 0,         150 mg/kg bw/day                       50% mortality in both           Hellwig et al.,
    150, 375 mg/kg bw/day,                                                 treatment  groups, dose-        1993
    5 times/week for 3                                                     dependent irritation in the
    months                                                                 forestomach and
                                                                           glandular stomach,
                                                                           purulent rhinitis, tubular
                                                                           nephroses

    Rat, Wistar, oral,
     drinking-water, 0, 9, 61,
     140, 331 mg/kg body
     weight/day for 3 months        331 mg/kg bw/day    140 mg/kg bw/day   Reduced water and food          Hellwig et al.,
                                                                           consumption in males            1993

    Rat, Wistar, oral,              140 mg/kg bw/day    61 mg/kg bw/day    Reduced water and food          Hellwig et al.,
     drinking-water, 0, 9, 61,                                             consumption in males            1993
     140, 331 mg/kg body
     weight/day for 12 months

                                                                                                                                                

    Table 5. (contd.)

                                                                                                                                                

    Species, route and dosage       LOELa               NOELa              Observed effects                Reference
                                                                                                                                                

    Rat, Wistar, oral,                                  78 mg/kg bw/day    No treatment-related            Hellwig et al.,
     drinking-water, 0, 8, 27,                                             toxic effects including         1993
      78 mg/kg body                                                        tumorogenicity
     weight/day for 26
     (males) or 28 (females)
     months

    Rat, inhalation, 80, 300        300 ppm             80 ppm             Nose irritation, lethargy       Gage, 1970
     ppm, 6 h/day 5                 (900 mg/m3)         (240 mg/m3)        reduced body weight gain
     days/week,
     20 exposures

    Rat, Fisher-344                 225 ppm (675        75 ppm             Decrease of adipose             Miller et al.,
    inhalation, 0, 25, 75,          mg/m3)              (225 mg/m3)        tissue in females, lesions      1979
     225 ppm, 6 h/day,                                                     of nasal mucosa
     5 days/week for 2 weeks


    Rat, Fisher 344                 75 ppm              25 ppm             Lesions of nasal olfactory      Miller et al.,
     inhalation, 0, 5, 25,          (225 mg/m3)         (75 mg/m3)         epithelium                      1981
     75 ppm, 6 h/day,
     5 days/week for
     13 weeks

    Rat, F-344, and mouse           75 ppm                                 Olfactory cell proliferation    Swenberg et al.,
     B6C3F1 inhalation,             (225 mg/m3)                            17-fold in mice, 4-fold in      1986
     75 ppm, 6 h/day, 5 days                                               rats
                                                                                                                                                

    Table 5. (contd.)

                                                                                                                                                

    Species, route and dosage       LOELa               NOELa              Observed effects                Reference
                                                                                                                                                

    Mouse, B6C3F1                   25 ppm                                 Decrease in body weight         Miller et al.,
     inhalation, 0, 25, 74,         (75 mg/m3)                             gain, lesions in nasal          1979
     223 ppm, 6 h/day                                                      mucosa
    5 days/week for 2 weeks

    Mouse, B6C3F inhalation         5 ppm               5 ppm              Atrophy, disorganization,       Lomax et al.,
     0, 5, 25 ppm for 6 or 22       22 h/day            6 h/day            necrosis of  the olfactory      1994
     h/day and 25 ppm for                                                  epithelium of nasal
     4.4 h/day for 2 weeks,                                                cavity.  Recovery after 6
     6 weeks recovery period                                               weeks except for mice
                                                                           exposed to 25 ppm for
                                                                           22 h/day where
                                                                           metaplasia was seen

    Mouse, B6C3F1                   5 ppm                                  Slight focal lesions of         Miller et al.,
     inhalation, 0, 5, 25,          (15 mg/m3)                             nasal olfactory                 1981
     75 ppm, 6 h/day 5                                                     epithelium
     days/week for 13 weeks
                                                                                                                                                

    a  LOEL = lowest-observed-effect level; NOEL = no-observed-effect level
    

    7.3.1  Oral

         Acrylic acid was administered via oral gavage to ten rats for 20
    days with doses increasing by 50% every fourth day (range:
    135 mg/kg to 684 mg/kg). Reduction in body weight gain and minor
    histopathological changes in the stomach were found at higher doses
    (Majka et al., 1974).

         In a 3-month study (Hellwig et al., 1993), groups of 10 male and
    10 female Wistar rats were gavaged, 5 times per week, with acrylic
    acid at doses of 150 or 375 mg/kg body weight. A control group of 10
    males and 10 females was gavaged with water. A high mortality rate was
    observed in experimental groups; 50% of both males and females in the
    low-dose group and 60% (males) and 90% (females) in the high-dose
    group died. Cyanosis, dyspnoea and irritation ulceration of
    forestomach and glandular stomach, purulent rhinitis and lung
    emphysema and alveolar hyperaemia were the main findings reported.
    Necrotizing tubular nephroses were seen in the animals that died
    during the study. The symptoms and histopathological findings were
    substantially the same in both groups, but they were less pronounced
    and observed in a smaller number of animals given acrylic acid at
    150 mg/kg body weight.

         Acrylic acid was given to Wistar rats in drinking-water for
    3 months as part of a 12-month study (Hellwig et al., 1993). Further
    details are given in section 7.4.

         In a subchronic study acrylic acid was incorporated into the
    drinking-water of rats (15/sex/group) for 3 months, resulting in doses
    of 0,83, 250 and 750 mg/kg per day. At the high and intermediate dose
    levels, reduction in body weight gain and changes in organ weights
    were observed. These effects coincided with a dose-related reduction
    in food and water consumption. At the 83 mg/kg dose, the only effect
    was a slight reduction in water consumption. No significant treatment-
    related histological effects were seen at any dose level (DePass et
    al., 1983).

    7.3.2  Inhalation

         In a short-term inhalation study (Gage, 1970) no adverse effects
    were observed in eight rats (four males and four females) exposed to
    240 mg/m3 (80 ppm) acrylic acid vapour, 6 h/day, 5 days/week for 20
    exposures. Eight rats (four males and four females) exposed at
    900 mg/m3 (300 ppm) showed signs of nasal irritation, lethargy and
    reduced body weight gain. Histological and haematological examinations
    were normal. Higher doses for shorter periods of time, i.e. 4500 mg/m3
    (1500 ppm) for 4 × 6 h, resulted in nasal discharge, lethargy,
    retarded weight gain and kidney congestion.

         In a 2-week subacute inhalation study by Miller et al. (1979a,
    1981a), F-344 rats and B6C3F1 mice (5/sex/group) were exposed to
    actual concentrations of 0, 75, 225 or 675 mg/m3 (0, 25, 75 or

    225 ppm) acrylic acid vapour for 6 h/day, 5 days/week for 2 weeks.
    Significant decreases in body weight gain were seen in exposed groups
    at 675 mg/m3. Decreased body weight gain in male mice at 75 and 
    225 mg/m3 was not considered to be exposure-related because of the low
    initial weight and unusually large weight gain in the controls. A
    reduction of adipose tissue was observed in female rats at 675 mg/m3.
    Rats had lesions of the nasal mucosa at 675 mg/m3. In mice lesions of
    the nasal mucosa were observed in 2/5 males and 4/5 females at 75 mg/m3
    and in all mice exposed to 225 or 675 mg/m3. The lesions were
    described as slight focal degeneration in the olfactory epithelium. No
    effects on lung or trachea were observed in rats or mice.

         Fifteen F-344 rats/sex/group and 15 B6C3F1 mice/sex/group were
    exposed to actual concentrations measured by infrared analysis of 0,
    15, 75 or 225 mg/m3 (0, 5, 25 or 75 ppm) acrylic acid (Miller et al.,
    1979a, 1981a). The exposure was 6 h/day for 5 days/week for 13 weeks.
    Animals were observed twice per day. There were no treatment-related
    deaths in rats or mice during the study period. Mean body weight gains
    of female mice in the 75 and 225 mg/m3 exposure groups after 12 weeks
    of exposure were significantly lower than controls. There were no
    significant differences in organ weights, clinical chemistry
    parameters, urinalysis parameters or gross pathology that could
    clearly be related to exposure. Slight focal degeneration of the nasal
    olfactory epithelium was observed in rats at 225 mg/m3 but no effects
    were seen at 15 or 75 mg/m3. In mice, there was a clear exposure-
    related increase in focal degeneration of the olfactory nasal
    epithelium at > 25 mg/m3. Lesions of the olfactory epithelium were
    detected histopathologically in all male and female mice in the 
    225 mg/m3 exposure group, in all males and 9/10 females in the
    75 mg/m3 group and in 1/10 males and 4/10 females in the
    15 mg/m3 group. The lesions were described as very slight at 15 mg/m3,
    slight at 75 mg/m3 and slight to moderate at 225 mg/m3.

         In a whole-body inhalation study, groups of 10 B6C3F1 female
    mice were exposed to 0, 15 or 75 mg/m3 (0, 5 or 25 ppm) acrylic acid
    vapour for 6 or 22 h/day for 2 weeks. An additional group of mice was
    exposed to 75 mg/m3 for 4.4 h/day for 2 weeks. No histopathological
    lesions in the nasal cavity were detected in mice exposed to 0 or 15
    mg/m3 for 6 h/day. Histopathological lesions were observed in the
    olfactory epithelium of the dorsal meatus of the nasal cavity in all
    other groups. These lesions included atrophy, disorganization,
    necrosis, desquamation of the epithelium and nasal cell hypertrophy.
    Lesions were more severe after the 22 h exposure at 75 mg/m3. After a
    6-week recovery period, the olfactory epithelium was normal except for
    mice exposed to 75 mg/m3 for 22 h/day where metaplasia was seen
    (replacement of olfactory epithelium with respiratory-like epithelium)
    (Lomax et al., 1994).

         Animals exposed to 720 mg/m3 (240 ppm) for 4 h/day, 6 days/week,
    for 5 weeks exhibited decreased body weight gain, increased urinary
    secretion of phenol red, reduced urine-concentrating ability, nasal
    discharge and increased reticulocyte count. Histopathological 
    examination revealed lesions of the gastric mucosa after repeated
    doses of acrylic acid. Inflammation of the upper respiratory tract was
    also seen (Majka et al., 1974).

    7.4  Long-term exposure

         Results of the studies of long-term repeated exposure effects to
    acrylic acid are presented in Table 5.

         In a 12-month study (Hellwig et al., 1993), Wistar rats
    (20/group/sex) were given drinking-water containing 120, 800, 2000 or
    5000 mg/litre (equivalent to doses of 9, 61, 140, 331 mg/kg body
    weight/day, respectively). Satellite groups (10 rats/group/sex) were
    treated concurrently for 3 months. Both in satellite groups and
    12-months exposure groups, a reduction in drinking-water and/or feed
    consumption and retarded body weight gain were observed in males at
    140 and 331 mg/kg per day (2000 and 5000 mg/litre), probably due to
    the unpalatability of acrylic acid at these concentrations.
    Differences between groups in the results of clinico-chemical,
    haematological and urinalytical examinations as well as in gross
    pathological and histopathological findings were not treatment-
    related. The no-observed-effect level (NOEL) was 61 mg/kg body weight
    (800 mg/litre).

         Acrylic acid was given to Wistar rats in drinking-water for 26
    (males) and 28 (females) months in a chronic/carcinogenicity study
    (Hellwig et al., 1993). Further details are given in section 7.7.

    7.5  Reproduction, embryotoxicity and teratogenicity

    7.5.1  Reproduction

         Results of key studies on the reproductive system are shown in
    Table 6.



        Table 6.  Reproductive effects of acrylic acid exposure in female rats and mice and developmental effects in their offspring

                                                                                                                                                

    Type of study      Species, route         Parental                       Developmental                       Observed effects
    and reference      and dosage
                                       LOEL               NOEL           LOEL            NOEL           Parental            Developmental
                                                                                                                                                

    Reproduction       Rat Fischer     250 mg/kg      83 mg/kg      750 mg/kg       250 mg/kg     Decreased body      Decrease in
    and development    344; oral,      bw/day         bw/day        bw/day          bw/day        weight and food     body weight gain
    (dePass et al.,    drinking-                                                                  consumption         of male and
    1983)              water; 0, 83,                                                                                  female pups,
                       250, 750 mg/kg                                                                                 decrease in
                       bw/day for 3                                                                                   liver, kidney,
                       months before                                                                                  heart and spleen
                       mating and                                                                                     weight in male
                       through-out                                                                                    pups and liver
                       gestation and                                                                                  weight in female
                       lactation                                                                                      pups

    Two-generation     Rat Wistar;     240 mg/kg      53 mg/kg      240 mg/kg       53 mg/kg      Fertility not       Retarded growth
    reproductive       oral, drinking- bw/day         bw/day        bw/day          bw/day        affected. Reduced   of F1 and F2 pups
    toxicity           water, 0, 500,                                                             food and water
    (BASF, 1994a)      2500, 5000 ppm                                                             consumption,
                       (53, 240,                                                                  reduced body
                       460 mg/kg/day)                                                             weights, gross
                                                                                                  and
                                                                                                  histopathological
                                                                                                  changes in stomach

    Developmental      Rat Sprague-    -              -             2.4 mg/kg                     No data             Increased
    toxicity           Dawley,                                      bw                                                resorptions
    (Singh et al.,     intraperitoneal                                                            and number
    1972)              0, 2.4, 4, 8,                                                                                  of gross and
                       8.0 mg/kg bw                                                                                   skeletal
                       i.p. on days 5,                                                                                abnormalities
                       10 and 15 of
                       gestation
                                                                                                                                                

    Table 6. (contd.)

                                                                                                                                                

    Type of study      Species, route         Parental                       Developmental                       Observed effects
    and reference      and dosage
                                       LOEL               NOEL           LOEL            NOEL           Parental            Developmental
                                                                                                                                                

    Developmental      Rat Sprague-    360 mg/m3      -             -               1080          Decreased           None
    toxicity           Dawley,         (120 ppm)                                    mg/m3         body weight,
    (Klimisch &        inhalation,                                                  (360 ppm)     food consumption
    Hellwig,           0, 40, 120,                                                                uterus-to-body
    1991)              360 ppm for                                                                weight; eye and
                       10 days during                                                             nose irritation
                       gestation
                       (days 6
                       through
                       15)

    Developmental      Rabbit New      180            90 mg/m3      -               --            Squamous            -
    toxicity           Zealand white,  mg/m3          (30 ppm)                                    metaplasia
    (Chun et al.,      inhalation, 0,  (60 ppm)                                                   erosions,
    1993)              30, 60, 125,                                                               ulcerations in
                       250 ppm (0,                                                                olfactory
                       90, 180, 375,                                                              epithelium
                       750 mg/m3)
                       during
                       gestation
                       (days 10-23)

    Developmental      Rabbit New      225 mg/m3      75 mg/m3      -               675           Perinasal,          None
    toxicity           Zealand white,  (75 ppm)       (25 ppm)                      mg/m3         perioral
    (Neeper-           inhalation                                                   (225 ppm)     wetness,
    Bradley &          0, 25, 75,                                                                 nasal
    Kubena, 1993)      225 ppm                                                                    congestion,
                       (0, 75, 225,                                                               blepharospasm

                       675 mg/m3)
                       during
                       gestation
                       (days 6-18)
                                                                                                                                                
    

         A one-generation study was conducted in which 10 male and 20
    female rats received acrylic acid orally, in drinking-water, at doses
    of 83, 250 or 750 mg/kg body weight per day for 3 months, after which
    the animals were mated; this formed part of the subchronic study
    reported in section 7.3.1. (DePass et al., 1983). Exposure was
    continued throughout gestation and lactation.

         Maternal toxicity at the two highest doses included decreased
    body weight gain and decreased food consumption. An apparent decrease
    in the fertility of females, as well as a reduction in gestation
    index, number of live pups/litter and percentage of pups weaned at the
    highest dose, was observed, but this difference was not statistically
    significant when compared with the control group. Unusually low
    fertility in the control group makes interpretation difficult.

         In a two-generation reproductive toxicity study (BASF, 1994a),
    Wistar rats were exposed to acrylic acid in drinking-water at levels
    of 500, 2500 or 5000 mg/litre. Acrylic acid did not impair
    reproductive function in either of the parental generations exposed to
    any dose level. Clear signs of toxicity, including reduced food and
    water consumption, reduced body weight and/or body weight gain, and
    gross and histopathological changes in the stomach, were observed in
    both parental generations exposed to 5000 mg/litre. At the 
    2500 mg/litre level, signs of toxicity were present in the second
    parental generation animals. No adverse effects were observed in either
    parental generation exposed to 500 mg/litre. Signs of developmental
    toxicity, including retarded growth of F1 and F2 pups and some
    delays in physical development of F2 pups only, were observed at 
    5000 mg/litre but less so at 2500 mg/litre. It is difficult to evaluate
    the role of acrylic acid in the decreased pup weights, because of the
    combined effects of reduced water consumption and the poor
    palatability of water containing acrylic acid. The greatest effects on
    body weight occurred during the period of early life around weaning.
    Developmental toxicity was not observed at 500 mg/litre. Thus, 
    500 mg/litre (equivalent to 53 mg/kg per day) was a NOEL for both
    generations of offspring and also a NOAEL for general toxicity in the
    second parental generation. The NOEL for general toxicity in the first
    parental generation was 2500 mg/litre (equivalent to 240 mg/kg per
    day).

         In a study by Vojtisek et al. (1991) cows were given 16 kg/day
    clover grass silage, treated with 3 litres acrylic acid/tonne, from
    day 57.6 ± 21.1 before parturition, for 107 days. Control groups of
    eight cows were given the same amount of silage, but treated with 4
    litres formic acid/tonne from day 55.5 ± 21.9 before parturition.
    Changes in clinical chemistry and haematological parameters observed
    in the course of the experiment (on days 0, 39, 65 and 107) were of no
    toxicological importance. No differences in colostrum density, body
    weight, clinico-chemical or haematological examinations of live calves
    were seen.

    7.5.2  Embryotoxicity and teratogenicity

    7.5.2.1  Oral

         In the experiment of DePass et al., (1983) (see also section
    7.5.1) there was a statistically significant decrease in body weight
    of the male and female pups at the highest dose (750 mg/kg per day),
    which was maternally toxic. The male pups also exhibited significant
    decreases in absolute and relative liver weights and in absolute
    kidney and heart weights at 750 mg/kg per day. The female pups showed
    a significant decrease in absolute and relative spleen weight and in
    absolute liver weight at the highest dose. There was an increase in
    relative brain weight in both sexes at this dose.

    7.5.2.2  Inhalation

         Groups of 30 pregnant Sprague-Dawley rats were exposed to nominal
    concentrations of 0, 120, 360 or 1080 mg/m3 (0, 40, 120, or 360 ppm)
    acrylic acid vapour for 6 h/day for 10 days during gestation (day 6 to
    day 15 of gestation) (Klimisch & Hellwig, 1991). There was clear
    evidence of maternal toxicity at 1080 mg/m3 consisting of eye and
    nose irritation, as well as reduced body weight gain and food
    consumption. The latter two effects were also seen at 360 mg/m3 and
    there was an indication of minimal maternal toxicity at 40 ppm
    (reduced body weight gain). There were no effects on preimplantation
    loss, the number of live fetuses and resorption, fetal size or on the
    appearance of the soft tissues and skeleton of the fetuses. This study
    identified a NOAEL for developmental effects of 1080 mg/m3 and a
    LOAEL for maternal toxicity of 1080 mg/m3.

         An inhalation developmental study has also been reported in
    rabbits (Neeper-Bradley & Kubena, 1993). In the range-finding study
    (Chun et al., 1993), groups of eight pregnant New Zealand white
    rabbits were exposed to 0, 90, 180, 375 or 750 mg/m3 (0, 30, 60, 125
    or 250 ppm) acrylic acid vapour for 6 h/day on days 10-23 of
    gestation. Three animals per group were necropsied on day 23 of
    gestation, and the remaining animals were examined on day 29.
    Exposure-related maternal toxicity at 375 and 750 mg/m3 was observed,
    including signs of nasal irritation and reduced body weight. Final
    body weight was reduced to a lesser degree in animals exposed to 90
    and 180 mg/m3. Histopathological examination of a single section of
    the nose showed adverse effects in the olfactory epithelium. The
    lesions included squamous metaplasia, epithelial erosion and
    ulceration of the epithelium, and increased in severity with
    increasing exposure concentration. The effect first appeared in the 
    90 mg/m3 group at day 23 and in the 180 mg/m3 group at day 29.
    In the main developmental study (Neeper-Bradley & Kubena, 1993), groups
    of 16 pregnant rabbits were exposed to 0, 75, 225 or 675 mg/m3 (0, 25,
    75 or 225 ppm) acrylic acid vapour for 6 h/day on gestation days 6-18.
    Maternal toxicity was evident in groups exposed to 225 or 675 mg/m3,
    but not to 75 mg/m3 (NOEL). Signs of nasal irritation, including
    perinasal wetness and nasal congestion, were observed. Significant
    decrements in food consumption and body weight gain were observed

    occasionally during exposure, but the body weights at the end of the
    exposure were not significantly affected. Histopathological 
    examination of maternal tissues was not performed. No exposure-
    related adverse effects were observed in the number of corpora lutea
    and total, viable or nonviable implantations; preimplantation loss;
    fetal length or weight; or on morphological abnormalities (skeletal
    or soft tissue). This study identified a NOEL for developmental
    effects of 675 mg/m3.

    7.5.2.3  Intraperitoneal

         When acrylic acid was injected intraperitoneally into pregnant
    female Sprague Dawley rats at doses of 0, 2.4, 4.8, or 8.0 mg/kg on
    days 5, 10 and 15 of gestation, the chemical was both embryotoxic and
    teratogenic (Singh et al., 1972). The number of resorptions and the
    number of gross and skeletal abnormalities increased with increasing
    acrylic acid concentration, and the NOEL was identified at the low
    dose (i.e. 2.4 mg/kg). Fetotoxicity (decreased number of live fetuses
    and mean fetal weight) was observed at a dose of 2.4 mg/kg. This study
    is difficult to interpret as the control groups treated with distilled
    water, normal saline and cotton-seed oil also showed gross and
    skeleton abnormalities. There was also no information about maternal
    toxicity.

    7.6  Mutagenicity and related end-points

    7.6.1  In vitro and insect studies

         Acrylic acid was found to be without mutagenic activity in five
    test strains of  Salmonella typhimurium with and without activation
    by rat and hamster liver microsomal preparations using both plate and
    liquid suspension assays (Lijinsky & Andrews, 1980). Although negative
    responses were reported in all strains, no cytotoxicity was observed
    at the concentrations tested (up to 1000 µg/plate).

         Acrylic acid was also evaluated for mutagenicity in the
    Salmonella/microsome preincubation assay using the standard protocol
    approved by the National Toxicology Program. Acrylic acid was tested
    at doses of 0, 10, 33, 100, 333, 1000 and 3333 µg/plate in four
     Salmonella typhimurium strains (TA98, TA100, TA1535 and TA1537) in
    the presence and absence of Aroclor-1254-induced rat or hamster liver
    S9. Acrylic acid was negative in these tests and the highest non-toxic
    dose level tested in any Salmonella test strain was 1000 µg/plate. The
    3333 µg/plate dose level was toxic and caused a complete clearing of
    the background lawn (Zeiger et al., 1987).

         In another study (Cameron et al., 1991) acrylic acid was also
    found to be negative in the Salmonella assay, both in the presence and
    the absence of both Aroclor-1254-induced rat or hamster liver S9 mix.

         Three mammalian gene mutation studies have been reported. No
    increase in mutation frequency was seen in a CHO/HPRT gene mutation

    assay with or without Aroclor 1254-induced rat liver S9 (McCarthy et
    al., 1992). The upper dose levels in this single experiment resulted
    in a reasonable amount of toxicity (survival reduced by up to 65-76%).
    In two mouse lymphoma L5178Y TK+/- studies positive results have been
    obtained. A concentration-related increase in mutant frequency was
    observed with and without rat liver S9 in association with an
    acceptable level of toxicity (Cameron et al., 1991). The authors did
    not state if there was any adjustment of pH. In the other study,
    conducted without exogenous metabolic activation, there were
    concentration-related increases in mutant frequency in two separate
    experiments in the presence of marked but not excessive toxicity.
    Small colonies predominated, which suggested a clastogenic effect;
    this was confirmed by chromosome analysis. Acrylic acid was tested at
    concentrations of 300, 450 and 500 µg/ml in this study but the authors
    did not state if there was any adjustment of pH  (Moore et al., 1988).

         A single experiment was conducted with CHO cells exposed to
    acrylic acid solutions adjusted to pH 7 at concentrations that reduced
    cloning efficiency by up to 58-65% (McCarthy et al., 1992). A
    concentration-related increase in the percentage of cells with
    chromosome aberrations, primarily chromatid breaks and exchanges, was
    observed in the presence and absence of rat liver S9. A positive
    result has also been briefly reported for this  in vitro chromosome
    aberration assay using CHL cells in the absence of exogenous metabolic
    activation (Ishidate, 1988).

         The effect of acrylic acid on unscheduled DNA synthesis (UDS) in
    rat hepatocytes has been investigated in one unreplicated assay
    (McCarthy et al., 1992). There was no increase in UDS at
    concentrations up to those closely approaching a very toxic level.
    Similar dose levels of acrylic acid in a single UDS experiment with
    SHE cells gave a negative result (Wiegand et al., 1989).

         Negative results have also been obtained in a micronucleus test
    and a transformation test, both with SHE cells, as well as in the
    Drosophila sex-linked recessive lethal assay (Wiegand et al., 1989;
    McCarthy et al., 1992).

         In a study by Segal et al. (1987), it was reported that acrylic
    acid forms 2-carboxyethyl adducts with adenine, guanine and thymine
    following  in vitro reaction with calf thymus DNA. These adducts are
    identical to those formed with the same bases following  in vitro
    reaction of carcinogen ß-propionolactone. The relevance of the results
    of this study is questionable because appropriate control treatments
    were not conducted and the 2-carboxyethyl adducts were formed after
    long treatment period.

         In contrast to the results above, Frederick & Reynolds (1989)
    found that incubation of the negatively charged acrylate anion with
    two representative nucleophiles, methylamine and imidazole, did not
    result in the formation of adducts of the acrylate ion to the
    nucleophile.

         It is suggested that binding of acrylic acid to cellular
    nucleophiles might be due to small amounts of the unionized acid in
    the equilibrium between acrylate anion and acrylic acid at cellular
    pH. However, this event is considered to be insignificant  in vivo,
    based upon the rapid metabolism and excretion of acrylic acid
    (Frederick & Reynolds, 1989).

    7.6.2  In vivo mammalian studies

         Preliminary results indicated no DNA adducts in the stomach and
    liver of rats after oral dosing (Sagelsdorf et al., 1988). Although
    DNA adducts were found in the skin of mice after dermal application,
    the investigators concluded that further work was needed to confirm
    the significance of these findings. No firm conclusions can therefore
    be drawn from these preliminary results.

         No increase in the incidence of chromosomal aberrations was
    observed in the bone marrow of rats following acute or repeated
    exposure to acrylic acid (McCarthy et al., 1992). Rats either received
    a single gavage dose of up to 1000 mg/kg acrylic acid or were exposed
    to up to 5000 mg/litre in the drinking-water for 5 days. There was no
    effect on the mitotic index of the bone marrow but there was evidence
    of systemic toxicity.

         Negative results were reported in a dominant lethal assay with
    mice following acute or repeated exposure to acrylic acid (McCarthy et
    al., 1992). Male CD-1 mice received either a single gavage dose of up
    to 324 mg/kg or daily gavage doses of up to 162 mg/kg for 5 days. The
    fact that the dose levels were selected not to exceed the LD1 for
    acute dosing and 0.5 LD1 for repeat dosing limits the value of this
    study.

    7.7  Carcinogenicity

         In a carcinogenicity study (Hellwig et al., 1993), Wistar rats
    (50/group/sex) were given acrylic acid in the drinking-water at
    concentrations of 0, 120, 400 or 1200 mg/litre (0, 8, 27, or
    78 mg/kg body weight per day, respectively) over 26 (males) or 28
    (females) months. The highest concentration was selected because of
    evidence of palatability problems at 2000 and 5000 mg/litre in an
    earlier chronic drinking-water study. At 1200 mg/litre there was some
    evidence for slightly reduced water consumption. In comparison with
    the controls, mortality was not increased by administering acrylic
    acid. No clear toxic effects were revealed in the groups. The few
    statistically significant differences in some haematological
    parameters between groups were considered to be of an incidental
    nature. The extensive histopathological examination revealed no clear
    treatment-related non-neoplastic tissue changes. The incidence and
    organ distribution of the tumours found in the groups treated with
    acrylic acid for 26/28 months did not differ from those of the
    controls. In this study the NOEL was 78 mg/kg body weight per day.

         It has been reported that when 25 µl of a 1% solution 
    (i.e. 0.25 mg) of acrylic acid was applied topically in acetone
    on the dorsal skin three times a week for their lifetime to 40
    male C3H/HeJ mice, no malignancies were observed at the site of
    application (De Pass et al., 1984).

         When 1 mg (14 µmol) of acrylic acid was applied topically in
    acetone 3 times a week to 30 female ICR/HA (currently designated
    Hsd:(ICR)Br) mice for 1.5 years, squamous cell carcinomas were
    observed in two of the mice (Cote et al., 1986). No conclusion can be
    drawn from this study, because only an abstract was issued, it was not
    subsequently published in full and an independent review of this study
    (Sivak, 1987) uncovered many inconsistencies and hence questioned the
    validity of the findings.

         Acrylic acid was assayed for carcinogenic activity in female
    Hsd:(ICR)bR mice by subcutaneous injection of 20 µmol (approx 1.4 mg) 
    in 0.05 µl trioctanoin, once a week for 52 weeks. The mice were then
    observed for an additional 93 days (total 450 days) when the survivors
    were killed. Two mice with sarcomas at the site of application were
    observed out of 30 mice (Segal et al., 1987). This would be an
    expected finding as an irritant solution was repeatedly given by
    subcutaneous injection. Injections for this length of time frequently
    result in sarcomas, no matter what the compound, because of repeated
    insult.

    7.8  Other studies

         In contrast to some of its esters, acrylic acid did not
    significantly decrease non-protein sulfhydryl content (NPSH) in the
    liver, blood or forestomach after oral dosing of rats with up to 
    400 mg/kg body weight (as 8% acrylic acid solution in 0.5% methyl-
    cellulose solution). However, a significant depletion of NPSH was
    observed in the glandular stomach at doses above 4 mg/kg (as 0.8%
    acrylic acid solution) (Miller et al., 1981b; De Bethizy et al., 1987).

         Acrylic acid was found to be ineffective in inducing GSH
    depletion, lipid peroxidation and haemolysis (Ferrali et al., 1989).

         It was reported that methylethyl- n-butyl and 2-ethyl-hexyl
    acrylates, when inhaled by male Wistar rats, induced hyperglycaemia
    but that acrylic acid was without effect (Vodicka et al., 1990).

         Rats received neutralized acrylic acid (50 mg/kg) intra-
    peritoneally for 8 consecutive days and were observed for central and
    peripheral nervous system effects. They showed a 25 % decrease in body
    weight gain but no signs of neurotoxicity (Kohriyama et al., 1994).

         In an  in vitro study, acrylic acid was more potent than
    acrylamide as an inhibitor of creatinine kenase (CK) activity in rat
    brain homogenates. However, when the two chemicals were given
    intraperitoneally 50 mg/kg per day for 8 days to rats, only acrylamide

    inhibited CK activity in the brain. The 14C level in the brain, 24 h
    after the injection of 14C-labelled chemicals, was more than seven
    times greater with acrylamide then with acrylic acid (Kohriyama et
    al., 1994).

         Single intraperitoneal injections of up to 2.2 mg/kg body weight
    of acrylic acid to Wistar rats had no effect on the hepatic activity
    of ornithine decarboxylase, which was measured for tumour-promoting
    activity (van de Zande et al., 1986).

         Laparotomies were carried out on pregnant Sprague-Dawley rats on
    day 13 of pregnancy under anaesthesia, and half of the developing
    fetuses were injected with 10, 100 or 1000 µg acrylic acid per fetus.
    One fetus injected with 100 µg acrylic acid showed slight
    hydrocephalus and microcephalia. A dose of 1000 µg resulted in 78%
    resorption (Slott & Hales, 1985).

         It was reported that acrylic acid interferes with incorporation
    of thymidine into DNA and uracil into RNA in  Staphylococcus aureus
    and  Escherichia coli (Glombitza & Heyser, 1971).

    7.9  Factors modifying toxicity

         No studies on factors modifying the toxicity of acrylic acid have
    been reported.

    8.  EFFECTS ON HUMANS

    8.1  General population exposure

    8.1.1  Acute toxicity

    8.1.1.1  Poisoning accidents

         There have been no reports on poisoning accidents in the general
    population or on the short- or long-term effects of acrylic acid on
    the general population.

    8.2  Occupational exposure

    8.2.1  Poisoning accidents

         There have been no reports on poisoning accidents due to
    occupational exposure.

    8.2.2  Effects of short- and long-term exposure

         Fowler (1990) described the case of a male chemical worker who
    developed acute generalized urticaria after working with acrylic acid
    and acrylate compounds. Immediate hypersensitivity testing showed a
    severe local reaction to 2% acrylic acid (which was apparently not
    irritant), but no reaction to other acrylate compounds. The acrylic
    acid used for testing was thought to be pure but it was not analysed
    for the presence of alpha,ß-diacryloxypropionic acid. Re-exposure of
    the worker in the workplace to acrylic acid resulted in generalized
    urticaria.

         No cross-sensitization to 0.1% acrylic acid was observed in six
    patients who had exhibited hypersensitivity to acrylate-based sealants
    (Conde-Salazar et al., 1988).

    9.  EFFECTS ON ORGANISMS IN THE ENVIRONMENT

    9.1  Microorganisms

         The toxic threshold (EC3) level for inhibition of growth of the
    bacterium,  Pseudomonas putida was 41 mg/litre after exposure for
    16 h to a neutralized solution of acrylic acid (Bringmann & Kühn,
    1980). Stewart et al. (1995) studied the anaerobic degradation of
    acrylic acid in 55-day tests in glucose-acetate enrichment culture. At
    100 mg/litre of acrylic acid there was minimal effect on acetate
    utilization by methanogens; concentrations of 500, 1000 and
    1500 mg/litre inhibited acetate utilization for a period of time
    before recovery.

         In a study of the effect of acrylic acid on the soil carbon
    cycle, it was shown that acrylic acid in soil (sandy loam soil), at
    levels of up to 100 mg/kg soil, had no effect on the respiration of
    the soil microflora. However, a concentration of 1000 mg/kg acrylic
    acid completely suppressed respiration (Hossack et al., 1992).

    9.2  Aquatic organisms

         The toxicity of acrylic acid to aquatic organisms is summarized
    in Table 7. Algae appear to be the most sensitive group with EC50
    values, based on growth, ranging from 0.04 to 63 mg/litre; and a NOEC
    for the most sensitive species of 0.008 mg/litre. Other acute toxicity
    studies range from 27 mg/litre (96-h LC50) for the rainbow trout to
    315 mg/litre (72-h LC50) for the golden orfe. A 96-h NOEC for glacial
    acrylic acid toxicity to rainbow trout was found to be 6.3 mg/litre
    based on a lack of sublethal/behavioural responses, e.g., quiescence,
    fish on bottom of test vessel, loss of equilibrium and erratic
    swimming, at this concentration (Bowman, 1990). Neutralized acrylic
    acid was found to be less toxic to daphnids than the non-neutralized
    solution (Bringmann & Kühn, 1982).

    9.3  Terrestrial organisms

         No data on terrestrial organisms have been reported.



        Table 7.  Toxicity of acrylic acid to aquatic organisms

                                                                                                                                                

    Species           Testa          Experimental                     Criticalb     Critical           Comments               Reference
                                     conditions                       end-point     acrylic acid
                                                                                    concentration
                                                                                    (mg/litre)
                                                                                                                                                

    Blue-green        CMIT           Exposure duration 8 days;        TT (EC3)      0.15               the toxic threshold    Bringmann &
    alga                             temp. 27°C; neutralized                                           with extinction        Kühn, 1978
    Microcystis                      pollutant solution; static                                        values > 3% lower
    aeruginosa                       closed flasks shaken once                                         than for controls
                                     a day; the
                                     concentration of the
                                     algae suspension measured
                                     turbidimetrically at 578 nm

    Green alga        CMIT           Exposure duration 7 days;        TT (EC3)      18                 as above               Bringmann &
    Scenedesmus                      temp. 27°C; neutralized                                                                  Kühn, 1980
    quadricauda                      pollutant solution; static
                                     closed flasks shaken once a
                                     day; the concentration of
                                     the algal suspension measured
                                     turbidi-metrically at 578 nm

    Green alga        CMIT           96-h static algal assay;         EC50          0.17               50% algal              Forbis, 1989
    Selenastrum                      acrylic acid exposure                                             growth
    capricornutum                    concentrations ranged from                                        inhibition
    (Printz)                         0.15 to 1.9 mg/litre

    Green alga        algal          Exposure duration                EC50          0.04               50% algal              BASF, 1994b
    Scenedesmus       inhibition     72 h                                                              biomass
    subspicatus       test                                                                             inhibition

                                                                      EC50          0.13               50% algal
                                                                                                       growth rate
                                                                      LOEC          0.016              inhibition

                                                                      NOEC          0.008
                                                                                                                                                

    Table 7. (contd)

                                                                                                                                                

    Species           Testa          Experimental                     Criticalb     Critical           Comments               Reference
                                     conditions                       end-point     acrylic acid
                                                                                    concentration
                                                                                    (mg/litre)
                                                                                                                                                

    Green alga        algal          Exposure duration                EC50          1.53               50% algal              SNF, 1995
    Chlorella         inhibition     72 h; nominal acrylic                                             biomass
    vulgaris          test (OECD     acid exposure                                                     inhibition
                      No. 201)       concentrations
                                     ranged from 0.2 to               EC50          63.0               50% algal
                                     4.7 mg/litre for                                                  growth rate
                                     biomass test and were                                             inhibition
                                     50 and 100 mg/litre
                                     for growth rate
                                     inhibition test

    Protozoan         CMIT           Exposure duration                TT (EC5)      20                 the toxic              Bringmann &
    Entosiphon                       72 h; temp. 25°C;                                                 threshold with         Kühn, 1982
    sulcatum                         pollutant solution                                                extinction
    (Stein)                          adjusted to pH 6.9;                                               values > 5%
                                     static closed flasks;                                             lower than for
                                     the number of                                                     controls
                                     protozoans was
                                     determined by
                                     means of cell counter

    Water flea        Daphnia        Exposure duration                EC50          765                after 24 h             Bringmann &
    Daphnia           immobilization 24 h; temp. 20°C;                                                 50% of exposed         Kühn, 1982
    magna             test           pH 7.8-8.2;                                                       organisms were
    (Straus)                         performed in 50 ml                                                immobilized in
                                     beakers covered with                                              neutralized test.
                                     filter paper;
                                     10 organisms/
                                     20 ml test solution;
                                     9 h illumination/
                                     15 h dark
                                                                                                                                                

    Table 7. (contd)

                                                                                                                                                

    Species           Testa          Experimental                     Criticalb     Critical           Comments               Reference
                                     conditions                       end-point     acrylic acid
                                                                                    concentration
                                                                                    (mg/litre)
                                                                                                                                                

                                                                      EC100         5000               100% immobilized
                                                                                                       after 24 h in
                                                                                                       neutralized test

                                                                                                       Acrylic acid in
                                                                                                       non-neutralized
                                                                                                       test
                                                                      EC50          54                 in non-neutralized
                                                                                                       test
                                                                      EC100         91

    Water flea      Daphnia          Dynamic test. Acrylic acid       EC50          95                 after 48 h 50% of      Burgess, 1990
    Daphnia magna   immobilization   exposure concentrations                                           exposed organisms
                    test             ranged from 7.9-110                                               were immobilized
                                     mg/litre.

                                     Exposure duration 48 h;          NOEC          23                 based on mortality
                                     temp. 19-20°C; pH 6.7-7.7;
                                     dissolved O2 7.9-8.0 mg/litre

    Golden orfe     L15-Fish test    Exposure duration                LC0           210                no lethality           Juhnke &
    Leuciscus idus  German           48 h; temp. 19-21°C; pH 7-8;                                                             Luedemann,
    melanotus       standard         dissolved O2                                                                             1978
                    method for the   > 5 mg/litre; 10-fish            LC50          315                death of 50%
                    contaminants     per 10 litre test                                                 of exposed
                    of water,        solution; continuous                                              fish
                    waste water      aeration
                    and sludge
                                                                      LC100         420                death of all
                                                                                                       exposed fish
                                                                                                                                                

    Table 7. (contd)

                                                                                                                                                

    Species           Testa          Experimental                     Criticalb     Critical           Comments               Reference
                                     conditions                       end-point     acrylic acid
                                                                                    concentration
                                                                                    (mg/litre)
                                                                                                                                                

    Rainbow trout   A flow-through   Exposure duration 96 h;          LC50          27                 death of 50%           Bowman,
    Oncorhynchus    toxicity test    measured glacial acrylic                                          of exposed             1990
    mykiss                           acid exposure                    NOEC          6.3                fish
                                     concentrations ranged                                             lack of
                                     from 6.3 to 90 mg/litre;                                          sublethal/
                                     20 fish per group                                                 behavioural
                                                                                                       responses

    Common carp                      Exposure duration                LC100         100                                       Nishiuchi,
    Cyprinus                         24 h                                                                                     1975
    carpio
                                                                                                                                                

    a    CMIT = Cell multiplication inhibition test
    b    TT = Toxicity threshold
    

    10.  EVALUATION OF HUMAN HEALTH RISKS AND EFFECTS ON THE
         ENVIRONMENT

    10.1  Evaluation of human health risks

    10.1.1  Exposure of the general population

         Very limited data are available on general population exposure.
    Exposure of the general population to acrylic acid may occur by the
    dermal route via contact with unreacted acrylic acid in household
    goods such as water-based paints or detergents. Exposure is also
    possible from inhalation due to evaporation of acrylic acid from
    paint.

         Exposure of the general population through drinking-water and via
    ambient air might be assumed. Exposure through drinking-water is
    possible from surface or groundwater contamination while inhalation
    exposure could occur in the vicinity of industrial emissions. However,
    there is no data on measured ambient air concentrations in populated
    areas and no data are available on acrylic acid concentrations in
    drinking-water. It was reported that acrylic acid might occur in
    wastewater effluent from industrial facilities at concentrations not
    exceeding 0.5 mg/litre. However, effluent levels of 2500 mg/litre were
    reported at a methyl acrylate production facility in India. After
    treatment acrylic acid concentration was below the limit of detention
    (0.1 mg/litre) in wastewater from a production facility in Europe.

         Food is an unlikely source of exposure to commercially derived
    acrylic acid because it is not known to be used in applications that
    involve direct contact with food.

    10.1.2  Occupational exposure

         The most important means of human exposure to acrylic acid is
    occupational exposure via inhalation and skin contact. On the basis of
    statistical estimates derived from a NIOSH survey conducted in
    1972-1974, 28 600 workers were potentially exposed to acrylic acid in
    the USA. More recently, NIOSH estimated that 96 500 workers were
    potentially exposed in the USA.

         One study conducted at a factory, where a number of chemicals
    including acrylic acid and a variety of acrylates and methacrylates
    were used, indicated that levels in air of acrylic acid and ethyl
    acrylate varied from 0.03 to 168 mg/m3 (0.01 to 56 ppm). However, the
    8-h TWA levels of most areas of the plant were well below the hygienic
    standard of 30 mg/m3 (10 ppm) for acrylic acid recommended by OSHA
    and ACGIH at the time of the study.

         Exposures of workers to acrylic acid have been compiled from four
    producing companies. Operators had a mean 8 h-exposure value of 
    0.48 mg/m3 (range of 0.03 to 3 mg/m3); during loading/unloading
    the mean 8 h-exposure was 0.39 mg/m3 (range of 0.27 to 1.98 mg/m3).

    10.1.3  Toxic effects

         Although a wide range of LD50 values has been reported, most
    data indicate that acrylic acid is of low to moderate acute toxicity
    by the oral route, moderate acute toxicity by the inhalation route and
    moderate acute toxicity by the dermal route.

         Acrylic acid is corrosive or irritant to skin and eyes. It is
    unclear what concentration is non-irritant. Although a 1% solution has
    been reported to irritate rabbit skin and eyes, no externally visible
    irritation was seen in one mouse study following repeated dermal
    application of 1%. Acrylic acid is also a strong irritant to the
    respiratory tract.

         Both positive and negative results have been obtained in skin
    sensitization tests with acrylic acid, but it appears that the
    positive findings may have been due to the impurity alpha,ß-
    diacryloxypropionic acid.

    10.1.3.1  Carcinogenic and mutagenic effects

         Both positive and negative results have been obtained in
     in vitro genotoxicity tests. Notably, acrylic acid was negative in
    the Ames test and  in vitro UDS assay, positive in a chromosome
    aberration assay (with pH adjustment) and in the  in vitro lymphoma
    cell assay. Chromosome damage was also demonstrated in one lymphoma
    assay. An  in vivo bone marrow chromosome aberration assay was
    negative. No firm conclusions can be drawn from an  in vivo
    DNA-binding study or from a dominant lethal assay. There are no
    satisfactory  in vivo genotoxicity data for sites of initial contact,
    e.g., nasal epithelium or skin.

         A single chronic cancer bioassay of acrylic acid, administered in
    drinking-water, has been reported. Male and female Wistar rats were
    given drinking-water containing 120, 400 or 1200 mg/litre (estimated
    doses were 8, 27 and 78 mg/kg body weight per day), after preliminary
    3- and 12-month studies showed reduced water consumption and body
    weight gain in groups of rats receiving drinking-water containing 2000
    or 5000 mg/litre. No systemic effects, including weight change or
    histopathology, and no increase in tumour incidence resulted from
    acrylic acid exposure. Although the lack of any toxic effects in this
    study suggests that the maximum tolerated dose was not achieved, it
    appears that the high dose in this study was approaching a maximum
    tolerance dose (MTD), based on the mild body weight effects noted at
    140 mg/kg per day in a 12-month study and at 240 mg/kg per day in a
    two-generation reproductive study. Apart from not reaching the MTD,
    the study used adequate number of animals (50), was well documented
    and reported complete histopathology.

         There has been no cancer bioassay conducted in a second species
    by the oral route, nor any inhalation cancer bioassay. Available data
    are inadequate to evaluate the carcinogenic potential of acrylic acid
    via the dermal route.

         There have been several chronic bioassays conducted on related
    compounds that are relevant to evaluation of the potential
    carcinogenicity of acrylic acid. Chronic inhalation studies have been
    reported for methyl acrylate, butyl acrylate and ethyl acrylate. All
    of these studies exposed rats to 0, 5, 25 or 75 ppm of the acrylates
    for 2 years, which was followed by complete necropsy and histopa-
    thological evaluation. The acrylate esters are rapidly metabolized to
    acrylic acid and alcohols by nasal, blood and other tissue carboxyl-
    esterases. In all of these studies a concentration-dependent increase
    in nasal olfactory degeneration was observed, and the response was
    very similar to the response observed in a subchronic inhalation study
    of acrylic acid. There were no treatment-related increases in tumour
    incidence in these studies. Although there may have been quantitative
    differences in the tissue doses of acrylic acid, the acrylate ester
    studies provide supportive evidence that carcinogenic effects do not
    occur in tissues exposed chronically to acrylic acid.

         Two cancer bioassays via oral exposure have been conducted with
    ethyl acrylate, a gavage study in F-344 rats and B6C3F1 mice (NTP,
    1986) and a drinking-water study in Wistar rats. The highest dose was
    similar in the two studies and produced lesions of the forestomach.
    However, the gavage study resulted in a dose-dependent increase in
    tumour incidence in both sexes of rats and mice while the drinking-
    water study did not. The gavage study suggests a potential for
    carcinogenic effects for ethyl acrylate, and, by extension, for the
    other acrylate esters and acrylic acid. The greater potency for this
    effect in a gavage study may relate to the contact site toxicity of
    these compounds. Gavage may not always be an appropriate exposure
    method for direct irritants because of the extremely high local doses
    that are achieved, compared to the local doses in a drinking-water
    study.

         A similar result can be seen in 3-month gavage and drinking-water
    studies. The drinking-water study caused mildly reduced body weight
    gain compared to controls, while the gavage study, at very similar
    doses, resulted in lethality in most of the dosed animals. These
    results suggest that the gavage route of exposure should play little
    role in the risk assessment of acrylic acid because human exposures
    are not likely to result in repeated high-concentration doses.

         Current practice requires strong evidence to conclude that a
    chemical is not a carcinogenic hazard, usually including adequate
    chronic bioassays in two species. A second species chronic bioassay is
    not available for acrylic acid, and the acrylate ester inhalation and
    drinking-water bioassays described above were carried out on rats. The
    existing acrylic acid bioassay is adequate and demonstrated no cancer
    effects. No epidemiological evidence regarding potential
    carcinogenicity of acrylic acid is available. Based on the available
    data, one cannot definitively conclude that acrylic acid does not pose
    a carcinogenic hazard to humans, although substantial relevant data do
    not suggest a cancer hazard.

    10.1.3.2  Non-cancer effects

     a)  Route-specific effects

         Both oral and inhalation exposures show effects at the site of
    contact. Inhalation exposures resulted in nasal effects in studies of
    2  weeks to 3 months in duration and at various exposure
    concentrations. High concentration drinking-water exposure to acrylic
    acid resulted in forestomach lesions. No other specific organ
    pathology has been consistently demonstrated in either oral or
    inhalation studies. Metabolic studies show rapid metabolism and
    clearance of acrylic acid that is similar for several routes of
    exposure, and there is no evidence of bioaccumulation of this
    chemical. The available evidence supports the conclusion that systemic
    toxicity is not likely to occur, and that the effects of oral and
    inhalation exposure can be treated as independent events with no
    additivity of doses received by the different routes of exposure. For
    this reason, guidance values will be derived separately for oral and
    inhalation routes.

     b)  Developmental and reproductive effects

         The toxicity data base for acrylic acid includes inhalation
    developmental studies in rats and rabbits and oral reproductive
    studies in rats. No specific reproductive or developmental effects
    were observed in any of these studies. The only effects observed
    included nasal effects in the inhalation studies and stomach lesions
    and reduced body weight gain in the drinking-water studies. Based on
    these results and the evidence for specific site-of-contact effects
    described above, the potential hazards for developmental and
    reproductive effects have been adequately studied and are not critical
    to the human health risk assessment.

     c)  Oral gavage studies

         As described above (section 10.1.3.1) the 3-month gavage and
    drinking-water studies showed important differences in toxicity,
    depending on the method of dosing. The drinking-water study revealed
    reduced body weight gain compared to controls, while the gavage study,
    at very similar daily doses, showed lethality in most of the dosed
    animals. Therefore, the gavage route of exposure should be of little
    importance in the risk assessment of acrylic acid because human
    exposures are not likely to result in repeated high-concentration oral
    doses.

     d)  Critical oral studies

         Potential critical studies include a 3-month drinking-water study
    in rats, 3-, 12- and 26- to 28-month drinking-water studies in rats,
    and a two-generation reproductive study in rats. Table 8 summarizes
    the effects seen in these studies and the determination of which
    effects are considered adverse.



        Table 8.  Summary of adverse effect levels in drinking-water studies on ratsa

                                                                                                                        

    LOAEL      NOAEL      Effectb                                                        Reference
                                                                                                                         

    750        250        Body weight; 81 and 84% of controls in males and females,      DePass et al., 1983
                          respectively, at 750; 95% of C in females at 250

    none       331        Body weight:                                                   Hellwig et al., 1993
                          males: 93% of C at 331;                                        (3-month study)
                          females: no effect

    331        140        Body weight:                                                   Hellwig et al., 1993
                          males: 91% of C at 331, 94% of C at 140;                       (12-month study)
                          females; no effect

    none       78         no effects                                                     Hellwig et al., 1993
                                                                                         (26- to 28-month studies)

    460        240        460: stomach irritation, body weight: 91% of C in F0 males,    BASF, 1993
                          65% of C in F1 pups, 85% of C in F1 (both sexes), 68% of C
                          in F2 pups

                          240: body weight: 89% of C in F1 pups, 88% of C in F2 pups
                                                                                                                         

    a    concentrations are given in mg/kg body weight per day
    b    C = control group; F0 = first parental generation; F1 = second parental generation
    

         A consistent finding throughout the drinking-water studies was
    decreased water consumption, probably due to taste aversion and
    sometimes accompanied by decreased food consumption. Reductions in
    body weight appear to parallel decreased water consumption and were
    worse in the pups in the reproductive study. The water consumption
    effect makes the body weight changes difficult to interpret as a
    direct toxic effect of acrylic acid, but the possibility that the
    effect was at least partly a direct result of acrylic-acid-induced
    irritation cannot be ruled out. The body weight effects are therefore
    considered to be adverse when the magnitude of the effect approaches a
    10% reduction. A somewhat larger change in the pup weight would be
    required to be considered adverse, because the largest weight
    decrements were seen at the end of active nursing and the beginning of
    weaning; they may be more severely affected by the reduced water
    consumption because of the greater maternal need for water intake
    during this time and the unknown effects of taste aversion on weaning
    behaviour. Based on these considerations and the presence of stomach
    histopathology at 460 mg/kg body weight per day, the NOAEL in the two-
    generation reproduction study was 240 mg/kg body weight per day. The
    NOAEL based on body weight changes in the 12-month studies was 
    140 mg/kg body weight per day.

     e)  Critical inhalation studies

         In a subchronic study, which is the only study that is
    potentially a critical study for inhalation, lesions in the nasal
    epithelium were seen in rats at 225 mg/m3 (75 ppm) and in mice at
    15 mg/m3 (5 ppm). The lesion in mice was described as very slight at
    15 mg/m3 (5 ppm), slight at 75 mg/m3 (25 ppm), and slight to
    moderate at 225 mg/m3 (75 ppm). Despite the mild nature of the
    response at 15 mg/m3 (5 ppm), there was a clear increase in incidence
    and severity of this lesion with increasing exposure concentration, so
    it must be considered adverse.

     f)  Progression of lesions

         There is suggestive evidence from both inhalation and oral routes
    of exposure that the effects caused by acrylic acid are largely
    determined by the exposure concentration and are relatively less
    affected by the duration of exposure in repeated exposure studies.

         In the oral studies, even if different LOAEL and NOAEL values
    could be defined by the 3-month and 12-month oral drinking studies,
    the effects on weight are similar for the two exposure durations. In
    inhalation studies in mice, the severity of the lesions in animals
    exposed for 6 h/day to 75 mg/m3 (25 ppm) was very similar in the
    2-week and the 90-day studies, although limited description of the
    lesions in the 2-week study makes this conclusion tenuous. Additional
    2-week studies included groups exposed to 15 and 75 mg/m3 (5 and 
    25 ppm) for 6 h/day. The 75 mg/m3 (25 ppm) group showed effects similar
    to those seen in the subchronic study, suggesting limited progression
    over this time-frame. The 15 mg/m3 (5 ppm) group exposed for 6 h/day 

    showed no effect after 2 weeks, so slight progression does occur at
    low concentrations, given that lesions were observed in the 90-day
    study. The 2-week study also included recovery groups, which showed
    that the lesions were completely reversed in animals exposed to 
    15 mg/m3 (5 ppm) for 22 h and 75 mg/m3 (25 ppm) for 6 h, but
    not in animals exposed to 75 mg/m3 (25 ppm) for 22 h/day.

         Comparison of the subchronic and chronic inhalation studies of
    the acrylate esters also supports the conclusion that there is limited
    progression of nasal lesions. Some progression of lesions does occur,
    but much less than would be predicted by an assumption of a constant
    concentration × time relationship.

    10.1.4  Risk evaluation

    10.1.4.1  Inhalation exposure

         The LOAEL of 15 mg/m3 (5 ppm) from the subchronic study is used
    as the basis for the guidance value. The appropriate uncertainty
    factors (UF) include 5 for inter-individual differences and 10 as a
    composite UF for interspecies, LOAEL to NOAEL and subchronic to
    chronic extrapolations. Reduced uncertainty for these aspects of the
    guidance value (GV) for inhalation results from the information
    discussed previously in this monograph. The inter-individual
    uncertainty is reduced because of the direct-acting nature of the
    toxicity, which does not involve metabolism. The uncertainty in
    extrapolating from a LOAEL to a NOAEL is reduced because the lesion at
    the LOAEL is very mild and reversible. The uncertainty in
    extrapolating from a subchronic to a chronic exposure is reduced
    because of the evidence discussed above showing limited progression.
    The interspecies uncertainty is reduced because of the direct-acting
    nature of the toxicity of acrylic acid and because the mouse is
    apparently very sensitive. The toxicity of acrylic acid is clearly
    limited to the site of deposition and is not dependent on metabolic
    activation. Since the deposition is controlled by physical
    interactions, there is little reason to expect significantly greater
    deposition in humans.

         Based on these considerations, the GVair for inhalation exposure
    of the general population may be calculated as follows:

    GVair = 15mg/m3 ×   6  ×   5   ×   1  = 54 µg/m3
                      24      5      50

    where:

    15 mg/m3 = LOAEL for mice

    6/24 and 5/7 = duration of exposure in h/day and weeks/day,
    respectively

    50 = total uncertainty factor

    10.1.4.2  Oral exposure

         For oral exposure the GV can be calculated based on NOAEL values
    in the 12-month oral study (140 mg/kg body weight per day), the two-
    generation reproductive study (240 mg/kg body weight per day) or the
    NOAEL in the chronic study (78 mg/kg body weight day). The chronic
    study is used to derive the GV because a lifetime exposure study is
    preferred to a short-duration study. The chronic study found no effect
    at the highest dose tested. The NOAEL is supported by the finding of
    adverse effects on body weight at 331 mg/kg body weight per day in the
    12-month study and body weight effects and stomach pathology in the
    two-generation reproductive study at 460 mg/kg body weight per day.
    With these supporting studies, the NOAEL from the chronic study can be
    used with confidence. A total uncertainty factor of 25 is based on a
    factor of 5 for inter-individual variability, and a factor of 5 for
    interspecies variability and for the lack of an adequate oral study in
    a second species. Reduced uncertainty factors are used for
    interspecies and inter-individual differences because of the direct-
    acting nature of the toxicity, as described in section 10.1.4.1. The
    need for a second species is suggested by the apparent differences in
    sensitivity between rats and mice in the subchronic inhalation study.

         Based on these considerations, the GVoral for drinking-water
    exposure may be calculated as follows:

         Tolerance intake  =  78  = 3.1 mg/kg
                              25

         From the above calculation a guidance value for oral intake of
    acrylic acid may be derived according to the following formula:

         GVoral = 3.1 × 64 ‰ 2 = 99 mg/litre

    where:

    3.1 mg/kg body weight per day = tolerable intake (TI)
    64 = average weight (kg) of human body
    25 = uncertainty factor
     2 = average intake of drinking water (litres/day)

         However, the Task Group expressed significant concern regarding
    the guidance value for oral intake calculated above, because of the
    difference in toxicity between drinking-water and gavage exposures.
    Exposure levels only 50-fold above the GV calculated above were lethal
    to 50% of the animals in the 90-day gavage study, and comparison with
    effects in the 90-day drinking-water study revealed a very significant
    difference between the two dosing methods. High doses taken over a
    short time period have much more severe effects.

         The concern is reduced by the fact that the local effects in the
    stomach might be determined by both concentration of delivered dose
    and total dose, so the same total dose delivered in more dilute
    solutions results in lesser effects, as shown for ethyl acrylate. The

    concentration in drinking-water needed to deliver the TI dose is
    probably far less than that required to cause direct effects, and is
    not a public health concern if small amounts are ingested over the
    course of the day, approximating to continuous exposure. The
    possibility remains that a large part of the TI could be delivered
    over a short time via drinking-water.

         Because of potential differences in individual drinking
    behaviour, the Task Group decided that a risk of effects still exists
    at the TI calculated above. For this reason an additional uncertainty
    factor of 10 was applied to derive the GV for drinking-water.

         Thus, the final guidance value for oral intake of acrylic acid
    is:

         GVoral = 99  mg/litre = 9.9 mg/litre
                  10

    10.2  Evaluation of effects on the environment

    10.2.1  Exposure

         Acrylic acid has been found to occur naturally in some species of
    marine alga. No quantitative data are available regarding
    environmental levels in ambient air or soil. It was reported that
    acrylic acid might occur in wastewater effluent from industrial
    facilities at concentrations not exceeding 0.5 mg/litre. Effluent
    levels of (2500 mg/litre) have been reported at a methyl acrylate
    production facility in India. After treatment acrylic acid was below
    the limit of detection (0.1 mg/litre) in wastewater from a production
    facility in Europe.

         Acrylic acid is miscible with water and, therefore, would not be
    expected to adsorb significantly to soil or sediment. Acrylic acid is
    eliminated from the environment by both abiotic and biotic
    degradation. Photolysis reactions are possible processes, but aerobic
    degradation constitutes the major route of breakdown. Microorganisms
    are capable of degrading acrylic acid under aerobic and anaerobic
    conditions.

         In soil, acrylic acid biodegrades very rapidly, the half-life
    being less than one day. There is no potential for long-range
    atmospheric transport of acrylic acid since it has an atmospheric
    lifetime of less than one month.

         Bioaccumulation of acrylic acid in organisms, based on the low
    octanol-water partition coefficient, is likely to be negligible. There
    has been no report of biomagnification of acrylic acid in food chains.

    10.2.2  Effects

         The toxicity of acrylic acid to bacteria and soil microorganisms
    is low.

         Algae are the most sensitive group of aquatic organisms studied,
    with EC50 values based on growth ranging from 0.04 to 63 mg/litre and
    a NOEC for the most sensitive species of 0.008 mg/litre. Acrylic acid
    has low to moderate acute toxicity for invertebrates and fish with
    LC50 values ranging from 27 to 315 mg/litre. The 96-h NOEC was
    6.3 mg/litre for rainbow trout, based on a lack of sublethal/
    behavioural responses.

         No data are available concerning the effects of acrylic acid on
    terrestrial organisms in the environment.

    10.2.3  Risk evaluation

         If released into the environment acrylic acid will partition to
    water where it will be readily degraded. Therefore, it is unlikely to
    pose a problem in the general environment. In the case of spills,
    acrylic acid is likely to cause localized mortality to aquatic
    organisms both from direct toxicity and oxygen depletion. There is
    likely to be a problem near to outfalls from plants discharging
    acrylic acid if there is inadequate sewage treatment. The toxicity of
    acrylic acid to bacteria and soil microorganisms is low. No data are
    available concerning the effects of acrylic acid on terrestrial
    organisms in the environment; however, data from laboratory mammals
    suggest a low risk.

    11.  CONCLUSIONS AND RECOMMENDATIONS FOR PROTECTION OF HUMAN HEALTH

    11.1  Conclusions

         The risks associated with occupational exposure to acrylic acid
    are low, as long as good industrial practice is followed. There is a
    lack of quantitative data on the levels of exposure for the general
    population. However, no obvious adverse effects on the general
    population have been identified.

         Acrylic acid poses minimal risk for the general environment
    except in the case of uncontrolled discharge.

    11.2  Recommendations for protection of human health

         It is recommended that exposure of the general population to
    acrylic acid in the ambient air and drinking-water does not exceed the
    guidance values given in this monograph.

    12.  FUTURE RESEARCH

    a)   Monitoring of acrylic acid concentrations in ambient air, water,
         soil and effluent should be carried out. Research should be
         undertaken to lower the analytical detection limit in water.

    b)   Further  in vivo studies on the genotoxic potential of acrylic
         acid at the initial site of contact are recommended.

    c)   The carcinogenicity of acrylic acid should be assessed in a well-
         controlled two-species bioassay (with both sexes) using proper
         exposure levels via inhalation or dermal exposure.

    d)   Better understanding of the relationship between persistent
         tissue damage and tumour formation would aid the risk assessment
         for an irritant chemical such as acrylic acid.

    e)   Additional research on the development of models describing the
         disposition and kinetics of acrylic acid is needed. Such models
         should focus on species differences in order to allow more
         confident extrapolation from animals to humans. In addition,
         models allowing comparison of acrylic acid dose for various
         acrylate esters would be useful to allow complete use of
         available data.

    f)   Since many workers are exposed to acrylic acid, epidemiological
         studies are needed, which should concentrate on the following
         end-points:

         i)   rhinitis, laryngitis and olfactory function;
         ii)  respiratory tract disease;
         iii) skin disease.

    13.  PREVIOUS EVALUATIONS BY INTERNATIONAL BODIES

         The carcinogenicity of acrylic acid has been evaluated by the
    International Agency for Research on Cancer (IARC, 1979, 1987). Data
    on the carcinogenicity of the compound for humans were considered
    inadequate. There was inadequate evidence for carcinogenicity in
    animals. Therefore, IARC considered acrylic acid not classifiable as
    to its carcinogenicity to humans.

    REFERENCES

    AAR (1987) Emergency handling of hazardous materials in surface
    transportation. Washington, DC, Association of America Railroads,
    Hazardous Systems (BOE), 11 pp.

    ACGIH (1988) Threshold limit values for chemical substances and
    physical agents and biological exposure indices for 1988-1989.
    Cincinnati, Ohio, American Conference of Governmental Industrial
    Hygienists.

    ACGIH (1990) Threshold limit values for chemical substances and
    physical agents and biological exposure indices for 1990-1991.
    Cincinnati, Ohio, American Conference of Governmental Industrial
    Hygienists, p 9.

    Amoore JE & Hautala E (1983) Odor as an aid to chemical safety: Odor
    thresholds compared with threshold limit values and volatilities for
    214 industrial chemicals in air and water dilution. J Appl Toxicol,
    3(6): 272-290.

    Andreoni V, Bernasconi S, Sorlini C, & Villa M (1990) Microbial
    degradation of acrylic acid.  Ann Microbiol, 40: 279-287.

    Archer G & Horvath MK (1991) Adsorption and desorption of acrylic acid
    to soils. Painesville, Ohio, Ricerca Inc., Department of Environmental
    Sciences (Document No. 3193-88-0214-EF-001).

    Atkinson R (1987) A structure-activity relationship for the estimation
    of rate constants for gas-phase reactions of OH radicals with organic
    compounds. Int J Chem Kinet, 19: 799-828.

    Atkinson R & Carter WPL (1984) Kinetics and mechanisms of the gas-
    phase reactions of ozone with organic compounds under atmospheric
    conditions. Chem Rev, 84: 437-470.

    Bandara BMR, Gunatilaka AAL, Kumar NS, & Wimalasiri WR (1988)
    Antimicrobial activity of some marine algae of Sri Lanka. J Natl Sci
    Counc (Sri Lanka), 16(2): 209-221.

    BASF (1958) [Report on biological tests for crude and pure acrylic
    acid.] Ludwigshafen, Germany, BASF AG, Toxicology Department
    (Unpublished report No. VII/365-366) (in German).

    BASF (1988) [Determination of the distribution coefficient log Pow of
    acrylic acid in 1-octanol/water at room temperature (25°C).]
    Ludwigshafen, Germany, BASF AG, Analytical Laboratory, pp 1-4 (in
    German).

    BASF (1992) Acrylic acid glacial P. Technical information monomers.
    Ludwigshafen, Germany, BASF AG.

    BASF (1993) [Examination of the biological degradability or the
    elimination potential, respectively, of acrylic acid (pure P)
    according to the experimental design of Zahn-Wellens (DUU/OM Project
    No. 92/2641/10/1).] Ludwigshafen, Germany, BASF AG (in German).

    BASF (1994a) Continuous administration in the drinking-water over 2
    generations (1 liter in the first and 1 liter in the second
    generation) (Project No. 71RO114/92011). Ludwigshafen, Germany, BASF
    AG.

    BASF (1994b) [Determination of the inhibitory effect of acrylic acid
    (pure) on the cell replication of the green algae  Scenedesmus
     supsicatus.] Ludwingshafen, Germany, BASF AG  (Unpublished
    experiment No. 94/0840/60/1) (in German).

    BG Chemie (1991) Acrylic acid. In: Toxicological evaluations, Volume
    2. Berlin, Springer-Verlag, pp 39-73.

    Black KA (1993) 14C-Acrylic acid. Comparative bioavailability study
    in male mice and rats -analysis of tissues. Spring House,
    Pennsylvania, Rohm and Haas Company, Toxicology Department (Report
    No. 93R-200).

    Black KA, Finch L, & Frederick CB (1993) Metabolism of acrylic acid to
    carbon dioxide in mouse tissues. Fundam Appl Toxicol, 21: 97-104.

    Black KA, Beskitt JL, Tallant MJ, & Frantz SW (1994) Disposition of
    acrylic acid (AA) in C3H mice after the oral, cutaneous and
    intravenous routes (Rohm and Haas Company, Spring House, PA and Bushy
    Run Research Center, Export, PA). Toxicologist, 14(1): 430 (Abstract
    1705).

    Black KA, Beskitt JL, Finch L, Tallant MJ, Udinsky JR, & Frantz ST
    (1995) Disposition and metabolism of acrylic acid in C3H mice and
    Fischer 344 rats after oral or cutaneous administration. J Toxicol
    Environ Health, 45: 291-311.

    Borzelleca JF, Larson PS, Hennigar GR, Huf EG, Crawford EM, & Smith RB
    (1964) Ethyl acrylate and methyl methacrylate: Studies on the chronic
    oral toxicity of monomeric ethyl acrylate and methyl methacrylate.
    Toxicol Appl Pharmacol, 6: 29-36.

    Bowen RL (1979) Adhesive bonding of various materials to hard tooth
    tissues. XVIII: Synthesis of a polyfunctional surface-active
    comonomer. J Dent Res, 58: 1101-1107.

    Bowman JE (1990) Acute flow-through toxicity of glacial acrylic acid
    to rainbow trout ( Salmo gairdneri). Columbia, Missouri, Analytical
    Bio-Chemistry Laboratories Inc., Aquatic Toxicology Division (Report
    No. 37343).

    Bretherick L (1985) Handbook of reactive chemical hazards, 3rd ed.
    Boston, Massachusetts, Butterworth, 351 pp.

    Bringmann G & Kühn R (1978) Testing of substances for their toxicity
    threshold: model organisms  Microcytis (Diplocystis) aeruginosa and
     Scenedesmus quadricauda.  Mitt Int Ver Limnol, 21: 275-284.

    Bringmann G & Kühn R (1980) Comparison of the toxicity thresholds of
    water pollutants to bacteria, algae, and protozoa in the cell
    multiplication inhibition test. Water Res, 14: 231-241.

    Bringmann G & Kühn R (1982) [Results of toxic action of water
    pollutants on  Daphnia magna Straus tested by an improved
    standardized procedure.] Z Wasser-Abwasser-Forsch, 15: 1-6 (in
    German).

    Brown RK, McMeekin TA, & Balis C (1977) Effect of some unicellular
    algae on  Escherichia coli populations in sea water and oysters. J
    Appl Bacteriol, 43: 129-136.

    Buckley LA, James RA, & Barrow CS (1984) Differences in nasal cavity
    toxicity between rats and mice exposed to acrylic vapor. Toxicologist,
    4(1): 1 (Abstract only).

    Burgess D (1990) Acute flow-through toxicity of acrylic acid to
     Daphnia magna. Columbia, Missouri, Analytical Bio-Chemistry
    Laboratories Inc. (Report No. 37344).

    Bysshe SE (1990) Bioconcentration factor in aquatic organisms. In:
    Lyman WJ, Reehle WF, & Rosenblatt DN ed. Handbook of chemical property
    estimation methods for environmental behaviour of organic compounds.
    Washington, DC, American Chemical Society, vol 15, pp 1-30.

    Cameron TP, Rogers-Back AM, Lawlor TE, Harbel JW, Seifried HE, &
    Dunkel VC (1991) Genotoxicity of multifunctional acrylates in the
    Salmonella/mammalian-microsome assay and mouse lymphoma TK+/- assay.
    Environ Mol Mutagen, 17: 264-271.

    Carpenter CP, Weil CS, & Smyth HF Jr (1974) Range-finding toxicity
    data: List VIII. Toxicol Appl Pharmacol, 28: 313-319.

    Casciery T & Clary J (1993) Acrylic acid health effects overview. In:
    Taylor TB, Murphy SR, & Hunt EK ed. Health effect assessments of the
    basic acrylates. Boca Raton, Florida, CRC Press, p 13.

    Chemical Marketing Reporter (1992) Acrylic grows at rapid pace, but so
    does the world's capacity. Chem Mark Report, July 20.

    Chou WL, Speece RE, & Siddiqi RH  (1978) Acclimation and degradation
    of petrochemical wastewater components by methane fermentation.
    Biotechnol Bioeng Symp, 8: 391-414.

    CHRIS (1985) CHRIS hazardous chemical data. Washington, DC, US
    Department of Transportation, US Coast Guard (CD-ROM version by
    Micromedex Inc., Denver, Colorado).

    CHRIS (1989) CHRIS hazardous chemical data. Washington, DC, US
    Department of Transportation, US Coast Guard (CD-ROM version by
    Micromedex Inc., Denver, Colorado.

    Chun JS, Kubena MF, & Neeper-Bradley TL (1993) Developmental toxicity
    dose range-finding study of inhaled acrylic acid vapor in New Zealand
    white rabbits. Export, Pennsylvania, Union Carbide Corporation (Bushy
    Run Research Center Report No. 92N1007).

    CITI (Japanese Chemicals Inspection and Testing Institute) ed. (1992)
    Acrylic acid. In: Biodegradation and bioaccumulation: Data of existing
    chemicals based on the CSCL Japan.  Tokyo, Japan Chemical Industry
    Ecology-Toxicology and Information Center, pp 2-83.

    Conde-Salazar L, Guimaraens D, & Romero LV (1988) Occupational
    allergic contact dermatitis from anaerobic acrylic reactants. Contact
    Dermatitis, 18: 129-132.

    Corrigan MA & Scott R (1988) Acrylic acid:  In vitro absorption
    through human and mouse skin. Macclesfield, United Kingdom, Imperial
    Chemical Industries PLC, Central Toxicology Laboratory (Report No.
    CTL/P/2047).

    Costellati L, Guglielmin AM, Vistoli O, Carboni GP, & Rambaldi R
    (1990) [Allergic contact dermatitis - evaluation of patch tests in
    animal fodder plant workers.] Med Lav,  81: 296-300 (in Italian).

    Cote IL, Hochwalt A, Seidman I, Budzilovich G, Solomon JJ, & Segal A
    (1986) Acrylic acid: Skin carcinogenesis in ICR/HA mice. Toxicologist,
    6: 235.

    Dean JA (1987) Handbook of organic chemistry. New York, McGraw-Hill
    Book Co., pp 1-76.

    De Bethizy ID, Udinsky JR, & Scribner HE (1987) The disposition and
    metabolism of acrylic acid and ethyl acrylate in male Sprague-Dawley
    rats. Fundam Appl Toxicol, 8(4) 549-561.

    DePass LR, Woodside MD, Garman RH, & Weil CS (1983) Subchronic and
    reproductive toxicology studies on  acrylic acid in the drinking water
    of the rat. Drug Chem Toxicol, 6(1): 1-20.

    DePass LR, Fowler EH, Meckley DR, & Weil CS (1984) Dermal oncogenicity
    bioassays of acrylic acid, ethyl acrylate and butyl acrylate. J
    Toxicol Environ Health, 14: 115-120.

    Douglas MT & Bell G (1992) Assessment of ready biodegradability of
    acrylic acid (Closed bottle test). Huntingdon, United Kingdom,
    Huntingdon Research Centre (HRC Confidential Report No. BMM 1/91329).

    D'Souza RW & Francis WR (1988) Vehicle and pH effects on the dermal
    penetration of acrylic acid:  in vitro- in vivo correlation.
    Toxicologist, 8: 831.

    EEC (1988) Methods for the determination of ecotoxicity,
    biodegradation. Activated sewage sludge respiration inhibition test.
    In: Council Directive of 18 November 1987 adapting to technical
    progress for the ninth time Directive 67/548/EEC on the approximation
    of the laws, regulations and administrative provisions relating to the
    classification, packaging and labelling of dangerous substances
    (88/302/EEC). Off J Eur Comm, L133: 118-122.

    Ekhina RS & Ampleeva GP (1977) [Combined effect of six acrylates on
    the sanitary status of a reservoir.] Vodemov, 1977: 157-164 (in
    Russian).

    Elf Atochem (1992) Norsocryl AA, acrylic acid specifications. Paris,
    Elf Atochem.

    Fassett DW (1963) Organic acids, anhydrides, lactones, acid halides
    and amides, thioacids. In: Patty FA ed. Industrial hygiene and
    toxicology, 2nd ed. New York, Wiley-Interscience, vol 2, p 1794.

    Fazzalari FA ed. (1978) Compilation of odor and taste threshold values
    data. Philadelphia, Pennsylvania, American Society for Testing and
    Materials, p 141.

    Ferrali M, Ciccoli L, & Comporti M (1989) Allyl alcohol-induced
    hemolysis and its relation to iron release and lipid peroxidation.
    Biochem Pharmacol, 38(1): 1819-1826.

    Finch L & Frederick CB (1992) Rate and route of oxidation of acrylic
    acid to carbon dioxide in rat liver. Fundam Appl Toxicol, 19:
    498-504.

    Forbis AD (1989) Acute toxicity of acrylic acid to  Selenastrum
     capricornutum Printz. Columbia, Missouri, Analytical Bio-Chemistry
    Laboratories Inc., Aquatic Toxicology Division (Report No. 37345).

    Fowler JH Jr (1990) Immediate contact hypersensitivity to acrylic
    acid. Dermatol Clin, 8: 193-195.

    Frantz SW & Beskitt JL (1993) 14C-Acrylic acid: comparative
    bioavailability study in male mice and rats. Export, Pennsylvania,
    Bushy Run Research Center (Report No. 92 N 1005).

    Frantz SW, Beskitt JL, Tallant MJ, & Black KA (1994) Disposition of
    acrylic acid (AA) in  Fischer rats after the oral, cutaneous and
    intravenous routes. Toxicologist, 14(1): 430 (Abstract 1704).

    Frederick CB & Reynolds CH (1989) Modeling the reactivity of acrylic
    acid and acrylate anion with biological nucleophiles. Toxicol Lett,
    47(3): 241-247.

    Frederick CB, Udinsky JR, & Finch L (1994) The regional hydrolysis of
    ethyl acrylate to acrylic acid in the rat nasal cavity. Toxicol Lett,
    70: 49-56.

    Gage JC (1970) The subacute inhalation toxicity of 109 industrial
    chemicals. Br J Ind Med, 27: 1-18.

    Ganou-Parfait B, Fahrasmane L, Celestine-Myrtil DA, Parfait A, & Galzy
    P (1988)  Micrococcus in rum technology in the French West Indies.
    Microbiol Aliments Nutr, 6(3): 273-277.

    Gelbke HP & Hofmann HTh (1979) [Report on testing for acute inhalation
    risk of acrylic acid (pure) in Sprague-Dawley rats.] Ludwigshafen,
    Germany, BASF AG, Department of Toxicology (in German).

    Ghanayem BI, Maronpot RR, & Matthews HB (1985) Ethyl acrylate-induced
    gastric toxicity: II. Structure-toxicity relationships and mechanism.
    Toxicol Appl Pharmacol,  80: 336-344.

    Ghanayem BI, Burka LT, & Matthews HB (1987) Ethyl acrylate
    distribution, macromolecular binding, excretion and metabolism in male
    Fischer 344 rats. Fundam Appl Toxicol, 9: 389-397.

    Glombitza KW (1970a) [Antimicrobial contents of algae: 2. Presence of
    acrylic acid in different sea algae.] Planta Med, 18(3): 210-221 (in
    German).

    Glombitza KW (1970b) [Antimicrobiol contents in algae: 3. Quantitative
    determination of acrylic acid in sea algae.] Planta  Med, 18(4):
    231-234 (in German).

    Glombitza KW (1979) Antibiotics from algae. In: Hoppe HA, Levring T, &
    Tanaka J ed. Marine algae in pharmaceutical science. Berlin, New York,
    Walter de Gruyter, pp 303-307.

    Glombitza KW & Heyser R (1971) [Antimicrobial constituent compounds in
    algae - Part 4: Effect of acrylic acid on respiration and synthesis of
    macromolecular in  Staphylococcus aureus and  Escherichia coli.]
    Helgoal Wiss Meeresunters, 22(3/4): 442-453 (in German).

    Grudzinski UJ (1988) [Substantiation of single maximum permissible
    levels of acrylic acid in the air of populated regions.] Gig I Sanit,
    9: 64-65 (in Russian).

    Hagan JV & Emmons HF (1991) Acrylic acid: Acute inhalation study in
    rats (Protocol No. 87P-240). Spring House, Pennsylvania, Rohm and Haas
    Company, Toxicology Department (Report No 87R-106).

    Halarnkar PJ & Blomquist GJ (1989) Comparative aspects of propionate
    metabolism. Comp Biochem Physiol, 92B: 227-231.

    Hansch C & Leo A (1987) The log P database. Claremont, California,
    Pomona College, p 391.

    Hawkins DR, Kirkpatrick D, Aikens PJ, & Saxton JE (1992) The
    metabolism of acrylic acid in soil under aerobic conditions.
    Huntingdon, United Kingdom, Huntingdon Research Centre (HRC
    Confidential Report No. 93A/920625).

    Hellwig J, Deckerdt K, & Freisberg KO (1993) Subchronic and chronic
    studies of the effects of oral administration acrylic acid to rats.
    Food Chem Toxicol, 31: 1-18.

    Herwig N (1978) Nutritious antibiotics. Mar Aquarist, 8(5): 48-50.

    Heyser R & Glombitza KW (1972) Effect of acrylic acid on glycolysis
    and citric acid cycle in bacteria: 5. Antimicrobiol components in
    algae. Arch Pharm, 305(11): 863-870.

    Hossack DJN, Thomas FJ, & Ruckman SM (1992) Acrylic acid: Effects on
    soil carbon cycle (respiration). Huntingdon, United Kingdom,
    Huntingdon Research Centre (HRC Confidential Report No. BMM 2/920228).

    Howard PH, Boethlings RS, Jarris WF, Meylan WM, & Midalenko EM (1991)
    Handbook on environmental degradation rates. Chelsea, Michigan, Lewis
    Publishers.

    Husain S, Sastry GSR, Prasad PR, & Sarma VR (1991) Differential pulse
    polarographic determination of residual acrylic acid in sodium
    polyacrylate. Electroanalysis, 3: 71-72.

    IARC (1979) Some monomers, plastics and synthetic elastomers, and
    acrolein. Lyon, International Agency for Research on Cancer, pp 47-71
    (IARC Monograph on the Evaluation of the Carcinogenic Risk of
    Chemicals to Humans, Volume 19).

    IARC (1987) Overall evaluations of carcinogenicity: An updating of
    IARC monographs, volumes 1 to 42. Lyon, International Agency for
    Research on Cancer, p 56 (Monographs on the Evaluation of the
    Carcinogenic Risk of Chemicals to Humans, Supplement 7).

    IRPTC (1992) IRPTC legal file. Geneva, United Nations Environment
    Programme, International Register of Potentially Toxic Chemicals.

    Ishidate M (1988) Data book of chromosomal aberration test  in vitro.
    Amsterdam, Oxford, New York, Elsevier Science Publishers.

    Juhnke I & Luedemann D (1978) [Results of testing of 200 chemical
    compounds for acute fish toxicity using the Golden Orfe test.]
    Z. Wasser Abwasser Forschung, 11(5): 61-164 (in German).

    Kalimo K, Jolanki R, Estlander T, & Kanerva L (1989) Contact allergy
    to antioxidants in industrial greases. Contact Dermatitis, 20:
    151-152.

    Kavaler AR (1987) Chemical profile on acrylic acid. Chem Mark Report,
    232(23): 62.

    Kirk-Othmer (1978-1984) Kirk-Othmer encyclopedia of chemical
    technology, Volumes 1-26,  3rd ed. New York, John Wiley and Sons.

    Klimisch HJ & Hellwig J (1991) The prenatal inhalation toxicity of
    acrylic acid in rats. Fundam Appl Toxicol, 16(4): 656-666.

    Klimisch HJ & Zeller H (1980) [Acute inhalation toxicity in the rat.]
    Ludwigshafen/Rhine, Germany, BASF AG, Department of Toxicology (in
    German).

    Klimkina NV, Bolding ZN, & Sergeev AN (1969) [Experimental basis for
    maximum permissible content of acrylic acid in reservoir waters.] Prom
    Zag Vodoemov, 9: 171-185 (in Russian, with English abstract).

    Kodama M & Ogata T (1983) Acrylic acid, as an antibacterial substance
    in scallop.  Bull Jpn Soc Sci Fish, 49(7): 1103-1107.

    Kohriyama K, Matsuoka M, & Igisu H (1994) Effects of acrylamide and
    acrylic acid on creatinine kinase activity in the rat brain. Arch
    Toxicol, 68(1): 67-70.

    Korenman IM & Lunicheva EV (1972) Distribution of acrylic acid between
    organic solvents and water. J Appl Chem (USSR), 45: 1101-1105.

    Kostanyan GG, Dadayan AA, & Safuryan GE (1969) [Polarographic
    determination of acrylic acid in commercial propionic acid.] Arm Khem,
    22: 1044 (in Russian with English abstract).

    Kutzman RS, Meyer GI, & Wolf AP (1982) The biodistribution and
    metabolic fate of (11C) acrylic acid in the rat after acute inhalation
    exposure or stomach intubation. J Toxicol Environ Health, 10(6):
    969-980.

    Lawrence WH, Bass GE, Purcell WP, & Autian J (1972) Use of
    mathematical models in the study of structure-toxicity relationships
    of dental compounds: I. Esters of acrylic acid and methacrylic acids.
    J Dent Res, 51: 526.

    Lijinsky W &  Andrews AW (1980) Mutagenicity of vinyl compounds in
     Salmonella typhimurium. Teratog Carcinog Mutagen, 1: 259-267.

    Lomax LG, Brown OW, & Frederick CB (1994) Regional histopathology of
    the mouse nasal cavity following two weeks of exposure to acrylic acid
    for either 6 or 22 h per day. Abstract presented at a Meeting on Nasal
    Toxicity and Dosimetry of Inhaled Xenobiotics: Implications for human
    health, Durham, North Carolina, 20-22 September 1993. Inhal Toxicol,
    6: 445-449.

    Lyman WJ, Reehl WF, & Rosenblatt DH (1982) Handbook of chemical
    property estimation methods: Environmental behavior of organic
    compounds. New York, McGraw-Hill Book Co., pp 9-65.

    McCarthy KL, Thomas WC, Aardema MJ, Seymour JL, Putman DL, Yang LL,
    Curren RD, & Valencia R (1992) Genetic toxicology of acrylic acid.
    Food Chem Toxicol, 30: 505-515.

    Mackay D & Peterson S (1981) Calculating fugacity. Environ Sci
    Technol, 15: 1006-1014.

    Magnusson B & Kligman AM (1969) The identification of contact
    allergens by animal assay:  The Guinea pig maximization test. J Invest
    Dermatol, 52: 268-276.

    Magnusson B, Blohm S, Fregert S, Hjorth N, Hovding G, Pirila V, & Skog
    E (1968)  Routine patch testing: IV. Supplementary series of test
    substances for Scandinavian countries. Acta Dermato-Venereol, 48:
    110-114.

    Majka J, Knobloch K, & Stetkiewicz J (1974) [Evaluation of acute and
    subacute toxicity of acrylic acid.] Med Prac, 25: 427-35 (in
    Polish).

    Mao J, Doane R, & Kovacs F Jr (1994) Separation of acrolein and its
    possible metabolites using different modes of high performance liquid
    chromatography. J Liq Chromatogr, 17: 1811-1819.

    Miller ML (1964) Acrylic acid polymers. In: Bikales NM ed.
    Encyclopedia of polymer science and technology, plastics, resins,
    rubbers, fibers. New York, Interscience Publishers, vol 1, pp 197-226.

    Miller RR, Ayres JA, & Jersey GC (1979a) Acrylic acid 90-day vapor
    inhalation study with rats and mice - Final report. Midland, Michigan,
    Dow Chemical Company, Toxicology Research Laboratory, Health and
    Environmental Science (Report No. 79RC-1024).

    Miller RR, Ayres JA, & Jersey GC (1979b) Acrylic acid 10-day vapor
    inhalation study with rats and mice - Final report. Midland, Michigan,
    Dow Chemical Company, Toxicology Research Laboratory, Health and
    Environmental Science (Report No. 79RC-1015).

    Miller RR, Ayres JA, Jersey GC, & McKenna MJ (1981a) Inhalation
    toxicity of acrylic acid.  Fundam Appl Toxicol, 1(3): 271-277.

    Miller RR, Ayres JA, Rampy LW, & McKenna MJ (1981b) The metabolism of
    acrylate esters in rat tissue homogenates. Fundam Appl Toxicol,
    1(6): 410-414.

    Miller RR, Young JT, Kociba RJ, Keyes DG, Bodner KM, Calhoun LL, &
    Ayers JA (1985) Chronic toxicity and oncogenicity bioassay of inhaled
    ethyl acrylate in Fischer 344 rats and B6C31 mice. Drug Chem Toxicol,
    8: 1-42.

    Mitchell DY & Petersen DR (1988) Inhibition of rat liver aldehyde
    dehydrogenases by acrolein. Drug Metab Dispos, 16: 37-42.

    Moiseeva TN, Kozulin SV, Kulikova LK, & Voronin SP (1991) Screening of
    strains decomposing acrylic acid and its derivatives. Soviet-
    Biotechnology, 1991(6): 119-125.

    Mok WSL (1989) Formation of acrylic acid from lactic acid in
    supercritical water. J Org Chem, 54(19): 4596-4602.

    Moore MM, Amtower A, Doerr CL, Brock KH, & Dearfield KL (1988)
    Genotoxicity of acrylic acid, methyl acrylate, ethyl acrylate, methyl
    methacrylate, and ethyl methacrylate in L5178Y mouse lymphoma cells.
    Environ Mol Mutagen, 11: 49-63.

    Nagasawa T, Nakamura T, & Yamada H (1990) Production of acrylic acid
    and methacrylic acid using  Rhodococcus rhodochrous J1 nitrilase.
    Appl Microbiol Biotechnol, 34(3): 322-324.

    Narayanasamy K, Shukla S, & Parekh LJ (1990) Utilization of
    acrylonitrile by bacteria isolated from petrochemical waste waters.
    Indian J Exp Biol, 28(10): 968-971.

    Nawaz MS, Franklin W, & Cerniglia CE (1993) Degradation of acrylamide
    by immobilized cells of  Xanthomonas maltophilia. Can J Microbiol,
    39(2): 207-212.

    Nawaz MS, Franklin W, & Cerniglia CE (1994) Degradation of aliphatic
    amide mixture by immobilized and nonimmobilized cells of  Pseudomonas
     sp. Environ Sci Technol, 28(6): 1106-1109.

    Neeper-Bradley TL & Kubena MF (1993) Developmental toxicity evaluation
    of inhaled acrylic acid vapor in New Zealand white rabbits. Export,
    Pennsylvania, Union Carbide Corporation (Bushy Run Research Center
    Report No. 92N1008).

    NIOSH (1974) National occupational hazard survey (NOES). Cincinnati,
    Ohio, National Institute for Occupational Safety and Health, Division
    of Surveillance, Hazard Evaluations, and Field Studies (NIOSH
    Publications No. 74-127).

    NIOSH (1977) National occupational hazard survey (NOES). Cincinnati,
    Ohio, National Institute for Occupational Safety and Health, Division
    of Surveillance, Hazard Evaluations, and Field Studies (NIOSH
    Publications No. 77-213).

    NIOSH (1989) Registry of toxic effects of chemical substances.
    Cincinnati, Ohio, National Institute for Occupational Safety and
    Health (CD-ROM version by Canadian Centre for Occupational Safety and
    Health, Hamilton, Ontario).

    NIOSH (1990) National occupational exposure survey (NOES). Cincinnati,
    Ohio, National Institute for Occupational Safety and Health, Division
    of Surveillance, Hazard, Evaluations, and Field Studies (Unpublished
    provisional data as of January 7, 1990).

    Nishikawa H, Hosomura H, Sonoda H, & Inagaki M (1979) [Behaviour of
    acrylamide in a soil-vegetation system.] Kenkyu Hokoku-Gifu-Ken Kogyo
    Gijutsu Senta, 11: 31-34 (in Japanese).

    Nishiuchi Y (1975) Toxicity of formulated pesticides to some
    freshwater organisms. Suisan Zoshoku, 23: 132.

    NLM (1989) Hazardous substances data bank. Bethesda, Maryland,
    National Library of Medicine (CD-ROM version by Micromedex Inc.,
    Denver, Colorado).

    NLM (1991) Hazardous substances data bank. Bethesda, Maryland,
    National Library of Medicine (CD-ROM version by Micromedex Inc.,
    Denver, Colorado).

    Noble RC & Czerkawski JW (1973) A gas-chromatographic method for the
    determination of low concentrations of acrylic acid in mixtures of C2
    to C5 fatty acids in biological materials. Analyst, 98: 122-125.

    NTP (1986) Carcinogenesis studies of ethyl acrylates (CAS No.
    140-88-5) in F344/N and B6C3F1 mice (gavage studies). Research
    Triangle Park, North Carolina, National Toxicology Program, 224 pp
    (NTP Technical Report Series No. 259; NIH Publication No. 87-2515).

    OHM/TADS (1989) Oil and hazardous material - Technical assistance
    Washington, DC, US Environmental Protection Agency (CD-ROM version by
    Micromedex Inc., Denver, Colorado).

    OSHA (1981) OSHA analytical methods manual. Part 1 - Organic
    substances: Method 28. Washington, DC, US Department of Labor,
    Occupational Safety and Health Administration.

    OSHA (1989) Department of Labor, Occupational Safety and Health
    Administration - 29 CFR, Part 1910: Air Contaminants. Final Rule. Fed
    Reg, 54(12): 2332-2983.

    Pahren HR & Bloodgood DE (1961) Biological oxidation of several vinyl
    compounds.  J Water Pollut Control Fed, 33(3): 233-238.

    Parker D & Turk JL (1983) Contact sensitivity to acrylate compounds in
    guinea pigs. Contact Dermatitis, 9(1): 55-60.

    Rao KS, Betso JE, & Olson KJ (1981) A collection of guinea pig
    sensitisation  test results -grouped by chemical class. Drug Chem
    Toxicol, 4: 331-351.

    Reininghaus W, Koestner A, & Klimisch HJ (1991) Chronic toxicity and
    oncogenicity of inhaled methyl acrylate and  n-butyl acrylate in
    Sprague-Dawley rats. Food Chem Toxicol, 29(5): 329-339.

    Riddick JA, Bunger WB, & Sakano T (1986) Organic solvents physical
    properties and methods of purification. In: Techniques of chemistry,
    4th ed. New York, Wiley-Interscience, vol 2, p 1325.

    Ruth JH (1986) Odour thresholds and irritation levels of several
    chemical substances: a review. Am Ind Hyg Assoc J, 47: A/143.

    Sagelsdorf P, Lutz WK, & Schlatter C (1988) Investigation of the
    potential for covalent binding of acrylic acid  in vivo after oral
    and dermal administration, preliminary results. Schwerzenbach bei
    Zurich, Switzerland, Toxicology Institute of the University of
    Zurich's Swiss Federal Institute of Technology (Report No.TOXETHZ
    1044K).

    Sanders JM, Burka LT, & Matthews HB (1988) Metabolism and disposition
    of  n-butyl acrylate in male Fischer rats. Drug Metab Dispos,
    16(3): 429-434.

    Sanseverino J, Montenecourt BS, & Sands JA (1989) Detection of acrylic
    acid formation in  Megasphaera elsdenii in the presence of 3-butynoic
    acid. Appl Microbiol Biotechnol, 30(3): 239-242.

    Sasaki S (1978) In: Hutizinger O ed. The scientific aspects of the
    chemical substance control law in Japan in aquatic pollutants
    transformation and biological effects. Oxford, New York, Pergamon
    Press, pp 283-298.

    Sax NI (1984) Dangerous properties of industrial chemicals, 6th ed.
    New York, Van Nostrand Reinhold Co., p 129.

    Sax NI & Lewis R (1989) Dangerous properties of industrial chemicals,
    7th ed. New York, Van Nostrand Reinhold Co., pp 71-72.

    Schultz H (1991) Beta-oxidation of fatty acid. Biochem Biophys,
    1081: 109-120.

    Schwartz BS, Doty RL, Moroe C, Frye R, & Barker S (1989) Olfactory
    function in chemical workers exposed to acrylate and methacrylate
    vapors. Am J Public Health, 79(5): 613-618.

    Segal A, Fedyk J, Meclchionne S, & Seidman I (1987) The isolation and
    characterization of 2-carboxyethyl adducts following  in vitro
    reaction of acrylic acid with calf thymus DNA and bioassay of acrylic
    acid in female Hsd:(ICR)Br mice. Chem-Biol Interact, 61: 189-197.

    Shah JF (1990) A hydrolysis study of 14C-acrylic acid. Painesville,
    Ohio, Ricerca Inc.

    Shanker R, Ramakrishna C, & Seth PK (1990) Microbial degradation of
    acrylamide monomer. Arch Microbiol, 154(2): 192-198.

    Shelton DR & Tiedje JM (1984) General method for determining anaerobic
    biodegradation potential. Appl Environ Microbiol, 47: 850-857.

    Sieburth JMN (1960) Acrylic acid, an "antibiotic" principle in
     Phaeocystis blooms in Antarctic waters. Science, 132: 676-677.

    Silver EH, Leith DE, & Murphy SD (1981) Potentiation by triorthotolyl
    phosphate of acrylate  ester-induced alterations in respiration.
    Toxicology, 22(3): 193-203.

    Simon P, Brand F, & Lemacon C (1989) Florisil sorbent sampling and ion
    chromatographic determination of airborn aliphatic carboxylic acids. J
    Chromatogr, 479: 445-451.

    Singh M & Thomas M (1985) Analysis of effluent from a methyl acrylate
    plant by gas chromatography. Indian J Environ Health, 27: 361-364.

    Singh AR, Lawrence WH, & Autian J (1972) Embryonic-fetal toxicity and
    teratogenic effects of a group of methacrylate esters in rats. J Dent
    Res, 51(6): 1632-1638.

    Singh HB, Jaber HM, & Davenport HE (1984) Reactivity/volatility
    classification of selected organic chemicals: Existing data. Menlo
    Park, California, SRI International, p 190 (EPA-600/3-84-082).

    Sittig M (1985) Handbook of toxic and hazardous chemicals and
    carcinogens, 2nd ed. Park Ridge, New Jersey, Noyes Data Corporation, p
    43.

    Sivak A (1987) Evaluation of acrylic acid mouse skin tumour bioassay
    and DNA adduct study performed at New York University Medical Center.
    New York, New York University (Report No. ADL/558.46 to the Celanese
    Corporation).

    Slott VL & Hales BF (1985) Teratogenicity and embryolethality of
    acrolein and structurally related compounds in rats. Teratology,
    32(1): 65-72.

    SNF (1995) Inhibition test (72 h) in freshwater unicellular algae.
    Licata-Messana L, SEPC (Société d'Ecotoxicologie et de Physico-
    Chimie). Saint Etienne, France, Société Nouvelle Floerger.

    Speece RE (1983) Anaerobic biotechnology for industrial wastewater
    treatment. Environ Sci Technol, 17: A416-A427.

    SRI International (1981) Production and use profile for CHIP of
    acrylic acid. Menlo Park, California, SRI International (US EPA
    Technical Directive 5.16).

    Staples RE (1993) Evaluation of the environmental fate and
    ecotoxicological parameters for several acrylic monomers. Washington,
    DC, Assessment Technologies BAMM.

    Stewart JM, Bhattacharya SK, Madura RL, Mason SH, & Schonberg JC
    (1995) Anaerobic treatability of selected organic toxicants in
    petrochemical wastes. Water Res, 29: 2730-2738.

    Swenberg JA, Gross EA, & Randall HW (1986) Localization and
    quantitation of cell proliferation following exposure to nasal
    irritants. In: Barrow CS ed. Toxicology of nasal passages. Washington,
    DC, Hemisphere Publishing Corporation, pp 291-300.

    Takamizawa K, Horitsu H, Ichikawa T, Tawai K, & Suzuki T (1993) Beta-
    hydroxypropionic acid production by  Byssochlamys sp grown on acrylic
    acid. Appl Microbiol Biotechnol, 40(2/3): 196-200.

    Tegeris AS, Balmer MF, Morton MF, Buckley IR, & Garner FM (1987)
    13-week mouse comparative skin irritation study with acrylic acid.
    Washington, DC, Basic Acrylate Monomer Manufacturers Association
    (Unpublished report).

    Tegeris AS, Balmer MF, Garner FM, Thomas WC, Murphy SR, McLaughlin JE,
    & Seymour JL (1988) A 13-week skin irritation study with acrylic acid
    in 3 strains of mice. Toxicologist, 8: 127.

    Union Carbide Corporation (1977) Toxicology studies: acrylic acid
    glacial. New York, Union Carbide Corporation, Industrial and
    Toxicology Department.

    US EPA (1981) Chemical hazard information profile: Acrylic acid (CAS
    No 79-10-7). Washington, DC, US Environmental Protection Agency, TSCA
    Assistance Division (EPA 749F9400.6).

    US ITC (1977) Synthetic organic chemicals - US production and sales.
    Washington, DC, International Trade Commission.

    US ITC (1983) Synthetic organic chemicals - US production and sales.
    Washington, DC, US International Trade Commission.

    US ITC (1985) Synthetic organic chemicals - US production and sales.
    Washington, DC, US International Trade Commission.

    US ITC (1986) Synthetic organic chemicals - US production and sales.
    Washington, DC, US International Trade Commission.

    US ITC (1987) Synthetic organic chemicals - US production and sales.
    Washington, DC, US International Trade Commission.

    US ITC (1988) Synthetic organic chemicals - US production and sales.
    Washington, DC, US International Trade Commission.

    US National Fire Protection Association (1986) Fire protection guide
    on hazardous materials, 9th ed. Boston, Massachusetts, US National
    Fire Protection Association, pp 40-42.

    Van der Walle HB, Seutter LPC, & Delbressine E (1982) Concomitant
    sensitization to hydroquinone and  p-methoxyphenol in the guinea
    pig; inhibitors in acrylic monomers. Contact Dermatitis, 8: 147-154.

    Van der Zande L, Kunnen R, Uijtewaal B, Van Wijk R, & Bisschop A
    (1986) Effect on hepatic ornithine decarboxylase of some food
    additives and synthetic elastomers. Food Addit Contam, 3(1): 57-62.

    Veith GD, DeFoe DL, & Bergstedt BV (1979) Measuring and estimating the
    bioconcentration factor of chemicals in fish. J Fish Res Board Can,
    36: 1040-1048.

    Verschueren K (1983) Handbook of environmental data of organic
    chemicals, 2nd ed. New York, Van Nostrand Reinhold Co., p 161.

    Vincent WJ & Guient V (1982) The development of air sampling and
    analytical methodology for determining occupational exposure. Am Ind
    Hyg Assoc J, 43(7): 499-504.

    Vodicka P, Gut I, & Frantick E (1990) Effects of inhaled acrylic acid
    derivatives in rats. Toxicology, 65(´): 209-222.

    Vojtisek B, Hronova B, Hamrik J, Jambor V, Zezula V, Zendulka I,
    Dvorak R, & Sisak M (1991) [The effect of clover silage treated with
    acrylic acid on selected indicators of metabolism in cows around the
    time of parturition and the status of their calves.] Vet Med (Praha),
    36: 273-280 (in Czech).

    Waegemaekers TH & van der Walle HB (1984)  Alpha,  beta-
    diacryloxypropionic acid, a sensitizing impurity in commercial acrylic
    acid. Dermatol Beruf Umwelt, 32: 55-58.

    Weast RC & Astle MJ (1985) CRC handbook of data on organic compounds,
    Volumes I and II. Boca Raton, Florida, CRC Press Inc., pp V1, 42, 57.

    Weast RC, Lide DR, Astle MJ, & Beyer WH ed. (1989) Acrylic acid. In:
    CRC handbook of chemistry and physics, 70th ed. Boca Raton, Florida,
    CRC Press, p C-57.

    Wegner WS, Reeves HC, Rabin R, & Ajl SI (1968) Alternate pathways of
    metabolism of short-chain fatty acids. Bacteriol Rev, 32: 1-26.

    Whanger PD & Matrone G (1967) Metabolism of lactic, succinic and
    acrylic acids by rumen microorganisms from sheep fed sulphur-adequate
    and sulphur-deficient diet. Biochem Biophys Acta, 136: 27-35.

    Wiegand HJ (1990) Species differences in the metabolism of  n-butyl
    acrylate. Naunyn- Schmiedebergs Arch Pharmacol, 341: 512 (Abstract
    47).

    Wiegand HJ, Schiffmann D, & Henschler D (1989) Non-genotoxicity of
    acrylic acid and  n-butyl acrylate in a mammalian cell system (SHE
    cells). Arch Toxicol, 63: 250-251.

    Windholz M ed. (1983) Merck index, 10th ed. Rahway, New Yersey, Merck
    & Co. Inc.

    Winter SM & Sipes IG (1993) The disposition of acrylic acid in the
    male Sprague-Dawley rat following oral or topical administration. Food
    Chem Toxicol, 31: 615-621.

    Winter SM, Weber GL, Gooley PR, MacKenzie NE, & Sipes IG (1992)
    Identification and comparison of the urinary metabolites of
    [1,2,3-13C3] acrylic acid and [1,2,3-13C3]propionic acid in the rat by
    homonuclear 13C nuclear magnetic resonance spectroscopy. Drug Metab
    Dispos, 20: 665-672.

    Wise HE & Fahrenthold PD (1981) Occurrence and predictability of
    priority pollutants in wastewater of the organic chemicals and
    plastics/synthetic fibers industrial categories - ACS 1981 National
    Meeting, Division of Industrial Chemistry Symposium on Treatability of
    Industrial Aqueous Effluents. Washington, DC, American Chemical
    Society.

    Zeiger E, Anderson B, Haworth S, Lawlor T, Mortelmans K, & Speck W
    (1987) Salmonella mutagenicity tests: III. Results from testing of 255
    chemicals. Environ Mutagen, 9: 1-110.

    1.  RESUME ET RECOMMANDATIONS

         L'acide acrylique est un liquide incolore qui dégage une odeur
    âcre et irritante à la température et à la pression ordinaires. Le
    seuil olfactif de l'acide acrylique est bas (0,20-3,14 mg/m3). Il est
    miscible à l'eau et à la plupart des solvants organiques.

         L'acide acrylique existe dans le commerce en deux qualités;
    l'acide acrylique technique et l'acide acrylique glacial. Il se
    polymérise facilement sous l'action de la chaleur, de la lumière ou en
    présence de métaux, c'est pourquoi un inhibiteur de polymérisation est
    ajouté aux produits du commerce.

         La production mondiale d'acide acrylique a été estimée à environ
    2 millions de tonnes en 1994. On l'utilise essentiellement comme une
    matière première pour la production d'esters acryliques, comme
    monomère pour la production de l'acide polyacrylique et de ses sels,
    comme comonomère avec l'acrylamide pour la préparation de polymères
    utilisés comme floculants, avec l'éthylène pour la préparation de
    résines échangeuses d'ions, l'ester méthylique sevant par aillleurs à
    la préparation d'un certain nombre d'autres copolymères.

         Il est possible de doser les résidus d'acide acrylique présents
    dans l'air et dans d'autres milieux par chromatographie en phase
    gazeuse, par chromatographie en phase liquide à haute performance ou
    encore par polarographie. Les limites de détection de ces méthodes
    sont de 14 ppm dans l'air et de 1 ppm dans les autres milieux.

         L'acide acrylique existe à l'état naturel dans certaines algues
    marines et on en a également trouvé dans les sécrétions du rumen chez
    les ovins.

         Comme il est miscible à l'eau, l'acide acrylique ne devrait pas
    s'adsorber de manière importante aux particules du sol ou aux
    sédiments. Dans le sol, les composés chimiques à faible constante de
    Henry sont essentiellement non volatils. Toutefois, la tension de
    vapeur de l'acide acrylique donne à penser qu'il se volatilise en
    surface du sol ou lorsque le sol est sec.

         L'acide acrylique libéré dans l'atmosphère réagit sur les
    radicaux hydroxyles et sur l'ozone produits par voie photochimique et
    se décompose alors rapidement. L'acide acrylique ne risque pas d'être
    transporté dans l'atmosphère sur une longue distance car sa durée de
    vie atmosphérique est inférieure à un mois.

         L'acide acrylique peut se former par hydrolyse de l'acrylamide
    monomère présent dans les déchets industriels enfouis dans le sol, en
    particulier dans des conditions d'aérobiose.

         Lorsqu'il est libéré dans l'eau, l'acide acrylique est facilement
    biodégradé. Sa destinée dans l'eau est liée à sa dégradation par voie
    chimique ou microbienne. Il est rapidement oxydé et risque donc de

    provoquer une désoxygénation des étendues d'eau dans lesquelles il est
    déversé en grandes quantités. On a montré que l'acide acrylique
    pouvait être décomposé dans des conditions d'aérobiose ou
    d'anaérobiose.

         On ne dispose d'aucune donnée quantitative sur les concentrations
    d'acide acrylique dans l'air ambiant, l'eau de boisson ou le sol.
    Toutefois, on sait qu'il est présent dans les effluents liquides
    déversés sur les sites où on le prépare par oxydation ménagée du
    propylène.

         On ne possède aucune donnée sur l'exposition de la population en
    général. Toutefois, les consommateurs peuvent être exposés à de
    l'acide acrylique libre présent dans des produits ménagers tels que
    certaines peintures à l'eau. Les personnes qui vivent à proximité
    d'unités de production d'acide acrylique ou de ses esters ou
    polymères, peuvent être exposées à l'acide acrylique présent dans
    l'air ambiant. L'absorption d'esters acryliques peut constituer une
    source potentielle d'exposition interne à l'acide acrylique.

         L'inhalation et le contact sont deux voies importantes
    d'exposition professionnelle.

         Quelle que soit la voie d'exposition, l'acide acrylique est
    rapidement résorbé et métabolisé. Il est métabolisé dans une forte
    proportion, principalement en acide 3-hydroxypropionique, en CO2 et
    en acide mercapturique qui sont éliminés ensuite dans l'air expiré et
    dans les urines. Du fait de sa métabolisation et de son élimination
    rapides, la demi-vie de l'acide acrylique est brève (quelques minutes)
    et il n'a donc aucune tendance à la bioaccumulation.

         On a fait état de valeurs très diverses pour la DL50, mais la
    plupart des données indiquent que l'acide acrylique présente une
    toxicité aiguë modérée à faible par la voie orale et une toxicité
    aiguë modérée par la voie respiratoire ou percutanée.

         L'acide acrylique est corrosif ou irritant pour la peau et les
    yeux. On ne sait pas avec précision au-dessous de quelle concentration
    il n'est plus irritant. Il est également très irritant pour les voies
    respiratoires.

         On a obtenu des résultats positifs et négatifs lors d'épreuves de
    sensibilisation cutanée avec de l'acide acrylique, mais il semble que
    les résultats positifs obtenus étaient dus à la présence d'une
    impureté.

         Lors d'études au cours desquelles des rats ont absorbé de l'acide
    acrylique dans leur eau de boisson, on a constaté que la dose sans
    effet nocif observable (NOAEL) était de 140 mg/kg de poids corporel
    par jour, le critère retenu étant la réduction du gain de poids sur
    12 mois, et de 240 mg/kg de poids corporel par jour, la critère retenu
    dans ce cas étant la présence d'anomalies histologiques au niveau de

    l'estomac. Le même type d'étude chronique sur des rats a montré qu'à
    la dose la plus élevée étudiée (78 mg/kg de poids corporel et par
    jour), il n'y avait aucun effet observable. La dose la plus faible
    provoquant un effet observable (LOAEL) a été de 15 mg/m3 (5 ppm) par
    la voie respiratoire chez des souris exposées pendant 90 jours à de
    l'acide acrylique, le critère retenu étant en présence de lésions
    nasales infimes chez les femelles. Des effets au niveau du nez ont
    également été observés chez des rats à la dose de 225 mg/m3, soit
    75 ppm, mais pas à celle de 15 ou 75 mg/m3 (5 ou 25 ppm).

         Les études de reproduction dont on connaît les résultats
    indiquent que l'acide acrylique n'est pas tératogène et qu'il n'a
    aucun effet sur la reproduction.

         Les épreuves de génotoxicité  in vitro ont donné des résultats
    positifs et des résultats négatifs. Une épreuve pratiquée  in vivo, à
    la recherche d'aberration chromosomique dans la moelle osseuse, a
    donné des résultats négatifs. Aucune conclusion définitive n'a pu être
    tirée d'une étude  in vivo sur la liaison à l'ADN ni de la recherche
    de mutations létales dominantes.

         Les données disponibles ne donnent pas de résultats indicatifs
    d'un pouvoir cancérogène de l'acide acrylique, toutefois ces données
    sont insuffisantes pour conclure qu'il n'y a aucun risque.

         On a signalé des cas d'intoxication dans la population générale,
    mais aucune étude épidémiologique en milieu professionnel n'a été
    publiée.

         Comme l'action toxique de l'acide acrylique se manifeste au point
    de contact, des valeurs guides distinctes sont recommandées pour
    l'exposition par voie orale et l'exposition par la voie respiratoire.
    On propose des valeurs guides de 9,9 mg/litre dans l'eau de boisson et
    de 54 µg/m3 dans l'air ambiant pour la population générale.

         L'acide acrylique est faiblement toxique pour les bactéries et
    les micro-organismes terricoles.

         Parmi les organismes aquatiques étudiés, ce sont les algues qui
    constituent le groupe le plus sensible, avec des valeurs de la CE50
    pour la croissance, qui vont de 0,04 à 63 mg/litre et une
    concentration sans effet observable (NOEC) chez l'espèce la plus
    sensible, qui est de 0,008 mg/litre. Pour la daphnie, les valeurs de
    la CE50 (critère : immobilisation) sont de 54 mg/litre sur 24 heures
    et de 95 mg/litre sur 48 heures. L'acide acrylique est plus toxique
    pour les daphnies que ses sels alcalins. En ce qui concerne la
    toxicité aiguë, les études toxicologiques sur des poissons ont donné
    les résultats suivants : de 25 mg/litre (CL50 à 96 heures) pour la
    truite arc-en-ciel, à 315 mg/litre (CL50 à 72 heures) pour l'orfe. En
    se basant sur l'absence de réponse sublétale et comportementale, on a
    observé que la concentration d'acide acrylique sans effet observable
    était de 6,3 mg/litre pour la truite arc-en-ciel.

         Du fait que son faible coefficient de partage entre l'octanol et
    l'eau, l'acide acrylique a peu de chances de subir une
    bioconcentration chez les organismes aquatiques. Par ailleurs, on n'a
    pas signalé de cas de bioamplification le long de la chaîne
    alimentaire.

         On ne dispose d'aucune donnée concernant les effets de l'acide
    acrylique sur les organismes terrestres.

    1.  RESUMEN Y RECOMENDACIONES

         El ácido acrílico es un líquido incoloro que desprende un olor
    acreirritante a temperatura y presión ambiente.  Su umbral de olor es
    bajo (0,20-3,14 mg/m3).  Es  miscible en agua y en la mayor parte de
    los disolventes orgánicos.

         El ácido acrílico está disponible en el comercio en dos
    calidades:  técnica y glacial.  Como se polimeriza fácilmente si se
    expone al calor, a la luz o a metales, los productos comerciales
    contienen un inhibidor de la polimerización.

         La producción mundial de ácido acrílico en 1994 se estimó en
    aproximadamente 2 millones de toneladas.  Principalmente se utiliza
    como materia prima en la producción de ésteres acrílicos, como
    monómero para ácidos y sales poliacrílicos, y como comonómero con
    acrilamida para polímeros que sirven de agentes de floculación, con
    etileno para polímeros de resina intercambiadora de iones, con éster
    metílico para polímeros y con ácido itacónico para otros copolímeros.

         Los residuos de ácido acrílico en el aire y en otros medios
    pueden cuantificarse mediante técnicas de cromatografía de gases,
    cromatografía líquida de alta resolución y polarografía.  Los límites
    de detección de esos métodos son de 14 ppm en el aire y 1 ppm en otros
    medios.

         Se ha notificado la presencia natural de ácido acrílico en algas
    marinas, y se le ha encontrado en el líquido ruminal de las ovejas.

         Por ser miscible en agua, no cabe prever que el ácido acrílico se
    adsorba de manera significativa en el suelo o en los sedimentos.  En
    el suelo, las sustancias químicas con bajas constantes de Henry son
    esencialmente no volátiles.  Sin embargo, la presión de vapor del
    ácido acrílico indica que éste se volatiliza del suelo superficial y
    del suelo seco.

         El ácido acrílico liberado en la atmósfera reacciona con los
    radicales hidroxilos y el ozono de origen fotoquímico, degradándose
    rápidamente.  El transporte atmosférico del ácido acrílico a grandes
    distancias no es posible, porque su permanencia en la atmósfera es
    inferior a un mes.

         El ácido acrílico puede formarse por hidrólisis del monómero
    acrilamida en desechos industriales presentes en el suelo,
    especialmente en condiciones aeróbicas.

         Liberado en el agua, el ácido acrílico se biodegrada rápidamente. 
    Su destino en el agua depende de la degradación química y microbiana. 
    El ácido acrílico se oxida rápidamente en el agua; descargado en
    grandes cantidades en una masa de agua, puede agotar el oxígeno.  Se
    ha demostrado que la degradación se produce en condiciones aeróbicas y
    anaeróbicas.

         No se dispone de datos cuantitativos sobre niveles de ácido
    acrílico en el aire ambiente, el agua potable o el suelo.  Sin
    embargo, se sabe que el ácido acrílico está presente en los efluentes
    de su producción por oxidación del propileno.

         No hay datos sobre la exposición de la población general.  No
    obstante, los consumidores podrían estar expuestos al ácido acrílico
    en productos de uso doméstico tales como las pinturas a base de agua. 
    La población residente en las cercanías de fábricas productoras de
    ácido acrílico o de sus ésteres o polímeros puede estar expuesta al
    ácido acrílico en el aire ambiente.  Una posible fuente de exposición
    interna puede ser el metabolismo de los ésteres del ácido acrílico
    absorbidos.

         La inhalación y el contacto con la piel son importantes vías de
    exposición ocupacional.

         Independientemente de la vía de exposición, el ácido acrílico se
    absorbe y metaboliza con rapidez.  Se metaboliza ampliamente, sobre
    todo en ácido 3-hidroxipropiónico, CO2 y ácido mercaptúrico, que se
    eliminan en el aire expirado y por la orina.  Debido a su rápido
    metabolismo y eliminación, la semivida del ácido acrílico es breve
    (minutos), por lo que no tiene potencial de bioacumulación.

         Aunque se ha notificado una amplia gama de valores de DL50, la
    mayor parte de los datos indica que el ácido acrílico tiene una
    toxicidad aguda de baja a moderada por vía oral, y moderada por
    inhalación o por vía cutánea.

         El ácido acrílico es corrosivo o irritante para la piel y los
    ojos.  No se sabe con certeza a qué concentración no es irritante. 
    También irrita fuertemente las vías respiratorias.

         En cuanto a la sensibilización de la piel al ácido acrílico, se
    han notificado resultados positivos y negativos, pero es posible que
    los positivos se deban a una impureza.

         En estudios con agua potable en ratas, el nivel sin efectos
    negativos observados (NOAEL) fue de 140 mg/kg de peso corporal al día
    para la reducción del aumento de peso corporal en un estudio de 12
    meses de duración, y de 240 mg/kg de peso corporal al día para las
    alteraciones histopatológicas en el estómago.  Un estudio de
    exposición crónica al agua potable en ratas no reveló efectos a la
    dosis más alta ensayada (78 mg/kg de peso corporal al día).  En
    ratones expuestos al ácido acrílico por inhalación durante 90 días se
    detectó un nivel inferior con efectos negativos observados (LOAEL) de
    15 mg/m3 (5 ppm), sobre la base de lesiones nasales muy ligeras en
    las hembras.  En las ratas se observaron efectos nasales a 225 mg/m3
    (75 ppm), pero no a 15 ni a 75 mg/m3 (5 ó 25 ppm).

         Los estudios de reproducción disponibles indican que el ácido
    acrílico no es teratogénico, ni tiene efecto alguno en la
    reproducción.

         En las pruebas de genotoxicidad  in vitro se han obtenido
    resultados tanto positivos como negativos.  Una prueba de aberración
    cromosómica en médula ósea  in vivo dio resultados negativos.  Un
    estudio  in vivo de unión de ADN y una prueba de dominancia letal no
    permitieron sacar conclusiones definitivas.

         Los datos disponibles no indican que el ácido acrílico sea
    carcinógeno, pero esos datos son insuficientes para concluir que no
    existe ningún riesgo de carcinogenicidad.

         No se han comunicado casos de intoxicación en la población
    general. Tampoco se han notificado estudios epidemiológicos
    ocupacionales.

         Puesto que la toxicidad del ácido acrílico afecta al lugar en que
    se produce el contacto, se recomiendan valores de orientación
    distintos para la exposición oral y por inhalación.  Para la población
    general se proponen valores de orientación de 9,9 mg/litro para el
    agua potable y de 54 œg/m3 para el aire ambiente.

         La toxicidad del ácido acrílico para las bacterias y los
    microorganismos del suelo es baja.

         Las algas son el grupo de organismos acuáticos más sensible entre
    los estudiados, con unos valores de CE50 , sobre la base del
    crecimiento, que van de 0,04 a 63 mg/litro y una concentración sin
    efectos observados (NOEC) para la especie más sensible de 0,008
    mg/litro.  Los valores de CE50 (basados en la inmovilización) para
     Daphnia magna son de 54 mg/litro (24 horas) y 95 mg/litro (48
    horas).  El ácido acrílico es más tóxico para los dáfnidos que la sal
    alcalina.  Estudios de toxicidad aguda en peces han dado resultados
    que oscilan entre 27 mg/litro (CL50 a las 96 horas) para la trucha
    arco iris y 315 mg/litro (CL50 a las 72 horas) para  Leuciscus idus. 
    La NOEC a las 96 horas para la toxicidad del ácido acrílico en la
    trucha arco iris se ha establecido en 6,3 mg/litro, sobre la base de
    la ausencia de respuestas subletales/comportamentales.

         Debido a su bajo coeficiente de reparto octanol/agua, es poco
    probable que el ácido acrílico sea objeto de bioconcentración en
    organismos acuáticos.  No se conocen casos de bioamplificación en
    cadenas alimentarias.

         No se dispone de datos sobre los efectos del ácido acrílico en
    organismos terrestres.
    



    See Also:
       Toxicological Abbreviations
       Acrylic acid (HSG 104, 1997)
       Acrylic acid (ICSC)
       Acrylic acid  (IARC Summary & Evaluation, Volume 71, 1999)