Concise International Chemical Assessment Document 21


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

    First draft prepared by
    Mr R. Cary, Health and Safety Executive, Liverpool, United Kingdom,
    Dr S. Dobson, Institute of Terrestrial Ecology, Huntingdon, United
    Kingdom, and
    Dr N. Gregg, Health and Safety Executive, Liverpool, 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, 2000

           The International Programme on Chemical Safety (IPCS),
    established in 1980, is a joint venture of the United Nations
    Environment Programme (UNEP), the International Labour Organisation
    (ILO), and the World Health Organization (WHO). The overall objectives
    of the IPCS are to establish the scientific basis for assessment of
    the risk to human health and the environment from exposure to
    chemicals, through international peer review processes, as a
    prerequisite for the promotion of chemical safety, and to provide
    technical assistance in strengthening national capacities for the
    sound management of chemicals.

           The Inter-Organization Programme for the Sound Management of
    Chemicals (IOMC) was established in 1995 by UNEP, ILO, the Food and
    Agriculture Organization of the United Nations, WHO, the United
    Nations Industrial Development Organization, the United Nations
    Institute for Training and Research, and the Organisation for Economic
    Co-operation and Development (Participating Organizations), following
    recommendations made by the 1992 UN Conference on Environment and
    Development to strengthen cooperation and increase coordination in the
    field of chemical safety. The purpose of the IOMC is to promote
    coordination of the policies and activities pursued by the
    Participating Organizations, jointly or separately, to achieve the
    sound management of chemicals in relation to human health and the

    WHO Library Cataloguing-in-Publication Data


           (Concise international chemical assessment document ; 21)

           1.Furaldehyde - toxicity 2.Risk assessment 3.Occupational
           exposure 4.Environmental exposure I.International Programme
           on Chemical Safety II.Series

           ISBN 92 4 153021 9       (NLM Classification: QD 305.A6)
           ISSN 1020-6167

           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 2000

           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.









        6.1. Environmental levels

        6.2. Human exposure

            6.2.1. Oral exposure

            6.2.2. Inhalation exposure

            6.2.3. Dermal exposure



        8.1. Single exposure

        8.2. Irritation and sensitization

        8.3. Short-term exposure

        8.4. Long-term exposure

            8.4.1. Subchronic exposure

            8.4.2. Chronic exposure and carcinogenicity

        8.5. Genotoxicity and related end-points

        8.6. Reproductive and developmental toxicity

        8.7. Immunological and neurological effects



        10.1. Aquatic organisms

        10.2. Terrestrial organisms


        11.1. Evaluation of health effects

             11.1.1. Hazard identification and dose-response assessment

             11.1.2. Criteria for setting guidance values for 2-furaldehyde

             11.1.3. Sample risk characterization

        11.2. Evaluation of environmental effects

             11.2.1. Predicted environmental concentration

             11.2.2. Predicted no-effect concentration

             11.2.3. Environmental risk factors



        13.1. Health surveillance advice

        13.2. Advice to physicians

        13.3. Spillage










        Concise International Chemical Assessment Documents (CICADs) are
    the latest in a family of publications from the International
    Programme on Chemical Safety (IPCS) -- a cooperative programme of the
    World Health Organization (WHO), the International Labour Organisation
    (ILO), and the United Nations Environment Programme (UNEP). CICADs
    join the Environmental Health Criteria documents (EHCs) as
    authoritative documents on the risk assessment of chemicals.

        CICADs are concise documents that provide summaries of the relevant
    scientific information concerning the potential effects of chemicals
    upon human health and/or the environment. They are based on selected
    national or regional evaluation documents or on existing EHCs. Before
    acceptance for publication as CICADs by IPCS, these documents undergo
    extensive peer review by internationally selected experts to ensure
    their completeness, accuracy in the way in which the original data are
    represented, and the validity of the conclusions drawn.

        The primary objective of CICADs is characterization of hazard and
    dose-response from exposure to a chemical. CICADs are not a summary of
    all available data on a particular chemical; rather, they include only
    that information considered critical for characterization of the risk
    posed by the chemical. The critical studies are, however, presented in
    sufficient detail to support the conclusions drawn. For additional
    information, the reader should consult the identified source documents
    upon which the CICAD has been based.

        Risks to human health and the environment will vary considerably
    depending upon the type and extent of exposure. Responsible
    authorities are strongly encouraged to characterize risk on the basis
    of locally measured or predicted exposure scenarios. To assist the
    reader, examples of exposure estimation and risk characterization are
    provided in CICADs, whenever possible. These examples cannot be
    considered as representing all possible exposure situations, but are
    provided as guidance only. The reader is referred to EHC 1701 for
    advice on the derivation of health-based guidance values.

        While every effort is made to ensure that CICADs represent the
    current status of knowledge, new information is being developed
    constantly. Unless otherwise stated, CICADs are based on a search of
    the scientific literature to the date shown in the executive summary.
    In the event that a reader becomes aware of new information that would
    change the conclusions drawn in a CICAD, the reader is requested to
    contact IPCS to inform it of the new information.

    1    International Programme on Chemical Safety (1994)
          Assessing human health risks of chemicals: deriviation of
          guidance values for health-based exposure limits. Geneva, World
         Health Organization (Environmental Health Criteria 170).


           The flow chart shows the procedures followed to produce a CICAD.
    These procedures are designed to take advantage of the expertise that
    exists around the world -- expertise that is required to produce the
    high-quality evaluations of toxicological, exposure, and other data
    that are necessary for assessing risks to human health and/or the

           The first draft is based on an existing national, regional, or
    international review. Authors of the first draft are usually, but not
    necessarily, from the institution that developed the original review.
    A standard outline has been developed to encourage consistency in
    form. The first draft undergoes primary review by IPCS to ensure that
    it meets the specified criteria for CICADs.

           The second stage involves international peer review by scientists
    known for their particular expertise and by scientists selected from
    an international roster compiled by IPCS through recommendations from
    IPCS national Contact Points and from IPCS Participating Institutions.
    Adequate time is allowed for the selected experts to undertake a
    thorough review. Authors are required to take reviewers' comments into
    account and revise their draft, if necessary. The resulting second
    draft is submitted to a Final Review Board together with the
    reviewers' comments.

           The CICAD Final Review Board has several important functions:

    -      to ensure that each CICAD has been subjected to an appropriate
           and thorough peer review;

    -      to verify that the peer reviewers' comments have been addressed

    -      to provide guidance to those responsible for the preparation of
           CICADs on how to resolve any remaining issues if, in the opinion
           of the Board, the author has not adequately addressed all
           comments of the reviewers; and

    -      to approve CICADs as international assessments.

    Board members serve in their personal capacity, not as representatives
    of any organization, government, or industry. They are selected
    because of their expertise in human and environmental toxicology or
    because of their experience in the regulation of chemicals. Boards are
    chosen according to the range of expertise required for a meeting and
    the need for balanced geographic representation.

           Board members, authors, reviewers, consultants, and advisers who
    participate in the preparation of a CICAD are required to declare any
    real or potential conflict of interest in relation to the subjects
    under discussion at any stage of the process. Representatives of
    nongovernmental organizations may be invited to observe the
    proceedings of the Final Review Board. Observers may participate in
    Board discussions only at the invitation of the Chairperson, and they
    may not participate in the final decision-making process.

    FIGURE 1


           This CICAD on 2-furaldehyde was based on a review of human health
    concerns (primarily occupational) prepared by the United Kingdom's
    Health and Safety Executive (Gregg et al., 1997), but it also contains
    environmental information. Hence, this document focuses on exposures
    via routes relevant to occupational settings but also includes an
    environmental assessment. Data identified up to January 1997 were
    covered in the review. A further literature search was performed up to
    December 1997 to identify any new information published since the
    review was completed, but no relevant studies were identified.
    Information on the nature of the peer review and availability of the
    source document is presented in Appendix 1. Information on the peer
    review of this CICAD is presented in Appendix 2. This CICAD was
    approved as an international assessment at a meeting of the Final
    Review Board, held in Washington, DC, USA, on 8-11 December 1998.
    Participants at the Final Review Board meeting are listed in Appendix
    3. The International Chemical Safety Card (ISCS 0276) produced by the
    International Programme on Chemical Safety (IPCS, 1993) has also been
    reproduced in this document.

           2-Furaldehyde (C5H4O2) (CAS No. 98-01-1) is a liquid with a
    pungent "almond-like" odour. It is found in trace amounts in a number
    of dietary sources and is produced commercially in batch or continuous
    digesters where pentosans from agricultural residues are hydrolysed to
    pentoses and the pentoses are subsequently cyclodehydrated to
    2-furaldehyde. Industrial uses include the production of resins,
    abrasive wheels, and refractories, refining of lubrication oils, and
    solvent recovery. 2-Furaldehyde is also used, in very small
    quantities, as a flavouring agent.

           2-Furaldehyde is present in many food items as a natural product
    or as a contaminant. Its presence in drinking-water and mothers' milk
    has been reported, but levels were not sufficient for quantification.

           Measured occupational inhalation exposures are available, and
    estimations have also been made using a knowledge-based computer
    system, Estimation and Assessment of Substance Exposure (EASE).
    Generally, airborne exposure in all industries is below 8 mg/m3
    (2 ppm), 8-h time-weighted average (TWA). There is insufficient
    information to predict 15-min TWA exposures for most industries;
    however, a 15-min TWA exposure between 1.2 and 6.8 mg/m3 (0.3 and 1.7
    ppm) has been estimated in the flavouring industry. No measured data
    are available for dermal exposure. EASE-predicted dermal exposures
    between 0.1 and 1 mg/cm2 per day have been calculated for most
    industries, with higher exposures of between 1 and 5 mg/cm2 per day
    calculated for the industries manufacturing refractories and abrasive

           Toxicokinetic data are limited, but there are indications that
    2-furaldehyde is readily absorbed via the inhalation and dermal
    exposure routes. Animal studies demonstrate that, following oral
    administration in rats, 2-furaldehyde is readily absorbed and rapidly
    excreted mainly via the urine, although some elimination via exhaled
    carbon dioxide also occurs. Metabolism is characterized by oxidation
    or acetylation of the aldehyde group, followed by glycine conjugation.
    2-Furoylglycine is the major urinary metabolite; other minor
    metabolites include furoic acid, furanacrylic acid, and furanacryluric

           In humans, absorption of the vapour via both the lungs and skin
    has been demonstrated. Metabolism in humans appears similar to that in
    rats, with the majority of the retained dose being excreted as urinary
    2-furoylglycine. Furoic acid and furanacryluric acid are also detected
    as minor metabolites. Dermal absorption from liquid 2-furaldehyde has
    also been observed.

           Acute toxicity data from animals are variable; overall, however,
    2-furaldehyde is toxic by the inhalation and oral routes (4-h LC50,
    940 mg/m3 [235 ppm]; oral LD50, about 120 mg/kg body weight), with
    no clear information in relation to the dermal route. Respiratory
    tract irritation and lung damage are consistently observed following
    single and repeated inhalation exposure. Skin and eye irritation are
    also reported. Apparently no throat or eye irritation was noted in
    humans exposed to 40 mg/m3 (10 ppm) for 8 h or 80 mg/m3 (20 ppm) for
    4 h. In animals, no-observed-adverse-effect levels (NOAELs) of 80
    mg/m3 (20 ppm) and 208 mg/m3 (52 ppm) in studies of up to 13 weeks'
    duration have been identified in hamsters and rabbits, respectively,
    for non-neoplastic effects. Malignant and benign tumours have been
    observed in rats and mice following oral exposure to 60 and 50 mg/kg
    body weight, respectively, for 103 weeks. 2-Furaldehyde is clearly
    genotoxic  in vitro in mammalian cells; although no firm conclusions
    can be drawn on the genotoxic potential of 2-furaldehyde  in vivo,
    the possibility that genotoxicity could contribute to the carcinogenic
    process cannot be discounted. These factors prevent the reliable
    determination of a NOAEL for 2-furaldehyde.

           The lack of available data to serve as a basis for estimation of
    indirect exposure of individuals to 2-furaldehyde from the general
    environment precludes the characterization of potential cancer risks
    for the general population.

           In the occupational environment, there is a potential risk of
    carcinogenic and genotoxic effects. The level of risk is uncertain; as
    a result, there is a continuing requirement to reduce exposure levels
    as much as is reasonably practicable with the technology that is
    currently available.

           There are no adequate data available regarding reproductive or
    developmental effects; hence, it is not possible to evaluate the risk
    to human health for these end-points.

           The highest reported emissions of 2-furaldehyde to the
    environment are from the wood pulp industry. 2-Furaldehyde will be
    released to the atmosphere from natural and anthropogenic wood

           No atmospheric effects are expected, as 2-furaldehyde is
    destroyed by reaction with hydroxyl radicals at a calculated
    atmospheric half-life of 0.44 days. In urban air, reaction with
    nitrate radicals may be an additional degradation process. Direct
    photo-oxidation may also occur. Low vapour pressure and low Henry's
    law constant suggest only slow volatilization of 2-furaldehyde from
    water and soil surfaces.

           In water, hydrolysis is not expected to occur at environmental
    pH. The low octanol/water partition coefficient (log  Kow 0.41)
    suggests low capacity for bioaccumulation. Sorption coefficients
    ( Koc) suggest little sorption to particulates and high mobility in

           2-Furaldehyde is readily biodegraded in aerobic systems using
    sewage sludge and in surface waters. Degradation also takes place
    under anaerobic conditions, with a range of bacteria and other
    microorganisms capable of degrading the compound as sole carbon
    source. At high concentrations (>1000 mg/litre), 2-furaldehyde
    inhibits growth and metabolic activity of unadapted anaerobic
    cultures. However, acclimation increases the capacity of anaerobic
    sludges to degrade the compound.

           The highest reported concentrations of 2-furaldehyde in
    industrial wastewaters are from sulfite evaporator condensate (about
    15% of the waste stream from wood pulp mills), at an average of 274
    mg/litre. A single study quantified 2-furaldehyde in indoor and
    outdoor air at around 1 µg/m3; other studies have detected but not
    quantified the compound.

           Toxic thresholds for a variety of microorganisms have been
    reported to range from 0.6 to 31 mg/litre. Acute LC50s for fish range
    from 16 to 32 mg/litre.

           Based on estimated predicted environmental concentrations from
    wood pulp waste (expected to be the worst case) and the application of
    an uncertainty factor of 1000 to the limited acute toxicity test data,
    2-furaldehyde emissions are expected to pose a low risk to aquatic
    organisms. There are no data on which to base a terrestrial risk
    assessment, but emissions to land are expected to be low.


           2-Furaldehyde (C5H4O2; molecular weight 96.09; CAS No.
    98-01-1) is a liquid with a pungent "almond-like" odour. Its
    structural formula is given below. A common synonym is furfural.
    Others include furfurol, 2-furanaldehyde, fural, furfuraldehyde, and
    2-furancarboxaldehyde. 2-Furaldehyde is colourless when freshly
    distilled, but it darkens in contact with air. It is completely
    miscible with most organic solvents, except saturated aliphatic
    hydrocarbons, and is soluble in water (one source quotes 83 g/litre).
    Its log  Kow is 0.41, its vapour pressure is 0.144 kPa at 20°C, and
    its dimensionless Henry's law constant (air/water partition
    coefficient) is 1.5 × 10-4 (HSDB, 1998). Additional physical/chemical
    properties are presented on the enclosed International Chemical Safety
    Card (ISCS 0276).


           The conversion factors for 2-furaldehyde in air at 20°C and 101.3
    kPa are as follows:

                         1 ppm    =  4.0 mg/m3
                         1 mg/m3  =  0.25 ppm


           Long- and short-term personal monitoring can be undertaken by
    pumped sampling through XAD-2 resin impregnated with 2-(hydroxymethyl)
    piperazine, desorbing with solvent (toluene), and analysing with gas
    chromatography (NIOSH, 1987). The working range is 1.2-22 mg/m3
    (0.3-5.5 ppm) for a 12-litre sample. Alternatively, a thermal
    desorption tube may be used, in either the pumped or diffusive mode
    (Patel et al., 1988). The working range for both is 4-40 mg/m3 (1-10
    ppm) for a 10-litre sample. Screening measurements can be made with
    colorimetric detector tubes, but these are unselective and not very

           Biological monitoring of workers exposed to 2-furaldehyde is
    possible by the analysis of 2-furoic acid (after alkaline hydrolysis
    of the metabolite furoylglycine) in urine (Sedivec & Flek, 1978).
    Although people not occupationally exposed to 2-furaldehyde have
    background levels of 2-furoic acid in hydrolysed urine samples (from
    dietary sources), these are low compared with those resulting from
    occupational exposure (Nutley, 1989). The biological exposure index of
    the American Conference of Government Industrial Hygienists is 200 mg
    2-furoic acid/g creatinine (200 µmol/mmol creatinine), and a study in
    the United Kingdom found that a 2-furoic acid concentration of over
    160 mg/g creatinine (160 µmol/mmol creatinine) was likely to be due to
    exposure to 2-furaldehyde at over 8 mg/m3 (2 ppm) (Nutley, 1989).

           More sensitive analytical methods are required for monitoring in
    food. Determination of the 2,4-dinitrophenylhydrazone derivative of
    2-furaldehyde by high-performance liquid chromatography gives high
    specificity, with a detection limit of 10 nmol/litre in spirits (Lo
    Coco et al., 1992). A fast, semi-automatic, stopped-flow injection
    analysis in which pretreatment of diversely coloured and turbid food
    samples is not necessary has been developed (Espinosa-Mansilla et al.,


           2-Furaldehyde is found in a number of dietary sources. Because of
    its formation during the thermal decomposition of carbohydrates,
    2-furaldehyde is found in numerous processed foods and beverages,
    including cocoa, coffee, tea, beer, wine, milk products, and bread
    (Maga, 1979). It is also found in some fruits and vegetables, and it
    is added as a flavouring agent to some foods. Industry in the United
    Kingdom is voluntarily withdrawing 2-furaldehyde from addition to
    food, although the chemical will still be present in food as a result
    of its production during the thermal processing of anything containing
    sugars. 2-Furaldehyde has also been found in the essential oils of
    camphor, citronella, sassafras, lavender, and lime (Dunlop & Peters,

           2-Furaldehyde is produced commercially in batch or continuous
    digesters where pentosans from agricultural residues, including corn
    cobs, oat hulls, rice hulls, and bagasse, are hydrolysed to pentoses
    and the pentoses are subsequently cyclodehydrated to 2-furaldehyde.
    2-Furaldehyde is shipped in steel tank cars, aluminium tank trucks,
    and steel cans. When stored in bulk, the storage tanks normally have a
    nitrogen blanket to prevent ingress of oxygen, which can cause
    chemical degradation of the material.

           Estimates of worldwide production are not available. US
    production in 1983 was about 52 000 t (HSDB, 1998). The estimated
    range of US production was 14 000-60 000 t in 1986, 2000-7000 t in
    1990, and 11 000-45 000 t in 1994 (US EPA, 1998). Although
    2-furaldehyde is not manufactured in the United Kingdom, it is
    estimated that industry in the United Kingdom used approximately 3000
    t in 1992. The official statistics indicate that imports into the
    United Kingdom for the previous four years were 2800 t (1988), 3500 t
    (1989), 3000 t (1990), and 3500 t (1991) (Gregg et al., 1997).

           Industrial uses of 2-furaldehyde are summarized in Table 1. About
    40% of 2-furaldehyde imported into the United Kingdom is used in the
    production of resins, abrasive wheels, and refractories. The rest is
    used in the refining of lubrication oils. Contacts with United Kingdom
    industry in 1992 indicated that there was unlikely to be any
    significant change in the pattern of use of 2-furaldehyde in the
    foreseeable future.

        Table 1: Industrial uses of 2-furaldehyde in the United Kingdom.

    Industry                     Uses

    1. Petrochemicals            As a selective solvent in 
                                 the production of lubricating oils

    2. Refractories              As a reactive wetting agent in the
                                 production of refractory components

    3. Resin manufacture         (a) Production of phenolic resins
                                 (b) Production of cashew nutshell polymers

    4. Abrasive materials        As a reactive wetting agent for the resin
                                 binder system in the production of abrasive wheels

    5. Solvent recovery          Steam distillation of spent 2-furaldehyde
                                 for reuse by industry sectors 1, 2, and 4

    6. Flavouring                Used in very small quantities in
                                 synthetic/natural oil blends


           The highest reported emissions of 2-furaldehyde to the
    environment are from the wood pulp industry, with release to the
    hydrosphere (section 6); release to water from other uses appears to
    be substantially lower. The compound would be released to the
    atmosphere from wood fires, a natural as well as anthropogenic source.

           In the atmosphere, 2-furaldehyde will exist predominantly in the
    vapour phase; the half-life for destruction by interaction with
    hydroxyl radicals has been calculated at 0.44 days (HSDB, 1998).
    Night-time destruction in the urban atmosphere may involve reaction
    with nitrate radicals (Carter et al., 1981). Direct photo-oxidation
    may occur in the atmosphere, based on experimental demonstration that
    concentrations of 2-furaldehyde in wood smoke were reduced by
    irradiation at sunlight and ultraviolet frequencies. Addition of
    nitrogen oxides to wood smoke increased the rate of disappearance of
    the compound (Kleindienst et al., 1986).

           Virtually no degradation occurred in a solution of 2-furaldehyde
    in distilled water over 30 days, suggesting that hydrolysis is not an
    important process at environmental pH (Ettinger et al., 1954). 

           A Henry's law constant of 0.37 Pa.m3/mol at 25°C has been
    calculated (HSDB, 1998), corresponding to a dimensionless Henry's law
    constant (air/water partition coefficient) of 1.5 × 10-4. These
    values indicate slow volatilization from water and damp soil surfaces;
    an estimated half-life for volatilization from a model river of 9.9
    days has been reported (HSDB, 1998).

           2-Furaldehyde has a reported log  Kow of 0.41, indicating low
    capacity for bioaccumulation; calculated bioconcentration factors were
    less than 1.2 (HSDB, 1998). The sorption coefficient ( Koc) can be
    calculated as between 1.05 (Organisation for Economic Co-operation and
    Development [OECD] Technical Guidance Manual) and 1.62 (Karickhoff et
    al., 1979), indicating little sorption to particulates and a high
    capacity for mobility in soil.

           2-Furaldehyde was readily biodegraded in an aerobic batch culture
    at 200 mg chemical oxygen demand (COD)/litre, with non-adapted sewage
    sludge showing 96.3% degradation within 120 h and a degradation rate
    of 37 mg COD/g per hour (Pitter, 1976). In a flow-through aerobic
    laboratory bioreactor at an initial concentration of 300 mg/litre, 98%
    degradation of 2-furaldehyde was reported using acclimated sewage
    sludge. Degradation also occurred at a concentration of 1000 mg/litre
    (Rowe & Tullos, 1980). 2-Furaldehyde was readily biodegradable in the
    Japanese Ministry of International Trade and Industry (MITI) test

    (Kawasaki, 1980). Wang et al. (1994) screened a range of
    microorganisms for their ability to degrade 2-furaldehyde and reviewed
    the earlier literature; some strains of the aerobic bacteria
     Escherichia coli,  Pseudomonas putida, and  Rhodococcus
     erythropolis and the yeast  Hyphozyma rosoeniger were able to
    degrade the compound to a greater or lesser degree. Inhibitory effects
    of 2-furaldehyde on  Pseudomonas putida were seen at concentrations
    of 0.1% and above, with complete inhibition at 1% with exposure for 30
    min (Kim et al., 1983).

           2-Furaldehyde at 1 mg/litre was degraded completely in water from
    the Great Miami, Little Miami, and Ohio rivers (USA) within 3 days
    under aerobic conditions (Ettinger et al., 1954).

           Under anaerobic conditions, 2-furaldehyde was completely degraded
    to methane by unacclimated sewage sludge within 30 days at an initial
    concentration of 580 mg/litre. The rate of methane production was
    initially slower than in controls, indicating some interference of the
    compound in the metabolism of the methanogenic bacteria. At an initial
    concentration of 1160 mg/litre, gas production ceased after 5 days,
    and none of the gas produced was methane; gas production did not
    resume within the 28 days of the test, indicating that this
    concentration was toxic to unacclimated microorganisms. Using
    acclimated sludge (which had received 2-furaldehyde at 310 mg/litre
    continuously for 8 months), full degradation occurred at 1160
    mg/litre. At 2320 mg/litre, 2-furaldehyde was initially degraded
    rapidly, but then gas production slowed for the remainder of the test
    (Benjamin et al., 1984). A strictly anaerobic bacterium isolated from
    a fermentor degrading sulfite evaporator condensate from wood pulp
    production was able to use 2-furaldehyde as sole carbon source; the
    organism was tentatively identified as  Desulfovibrio sp. (Brune et
    al., 1983).  Methanococcus deltae was found to be able to use
    2-furaldehyde as sole carbon source, degrading the compound to
    furfuryl alcohol at initial concentrations of 5 and 10 mmol/litre (480
    and 960 mg/litre); however, growth of the bacterium was inhibited at
    concentrations of 20 and 25 mmol/litre (1920 and 2400 mg/litre). Other
    methanogenic bacteria ( Methanobacterium thermoautotrophicum,
      Methanosarcina barkeri, and  Methanococcus thermolithotrophicus)
    were unable to degrade the compound (Belay et al., 1997).


    6.1  Environmental levels

           2-Furaldehyde was detected in 1 out of 204 surface water samples
    from heavily industrialized areas in the USA at 2 µg/litre (detection
    limit 1 µg/litre) and in 1 out of 13 samples from the Lake Michigan
    basin, USA, at 2 µg/litre in the late 1970s (HSDB, 1998).

           2-Furaldehyde was not detected (detection limit 0.4 ng/litre) in
    33 samples of surface waters in the 1996 monitoring of the general
    environment in Japan (Japan Environment Agency, 1998). However, the
    compound was detected in 6 out of 15 air samples (detection limit 40
    ng/m3) in two cities (range 42-120 ng/m3). The analytical method was
    not stated in the publication.

           Levels of 2-furaldehyde in sulfite evaporator condensate, which
    represents about 15% of the wastewater flow from pulp mills, have been
    reported to range between 10 and 1280 mg/litre (Ruus, 1964) and
    between 179 and 471 mg/litre (average 274 mg/litre) (Benjamin et al.,
    1984). The 2-furaldehyde derives from pentoses in the wood pulp and is
    formed during the waste treatment in the evaporator. 2-Furaldehyde was
    detected in the wastewater of a synthetic rubber plant at 1.7 µg/litre
    (Keith, 1974).

           2-Furaldehyde was detected but not quantified in the air above
    the Black Forest, Germany, in 1984-85 (Juttner, 1986). Although
    2-furaldehyde has been identified in vehicle exhaust, it was not
    detectable in air sampled from a road tunnel in the USA (Hampton et
    al., 1982). The compound has been identified in smoke from burning
    wood (Lipari et al., 1984; Kleindienst et al., 1986). Mean
    concentrations of 2-furaldehyde measured in indoor and outdoor air in
    suburban New Jersey, USA, in summer 1992 were 1.06 µg/m3 (0.27 ppb)
    and 0.67 µg/m3 (0.17 ppb), respectively. The presence of the compound
    in indoor air was presumed to be from emissions during cooking (Zhang
    et al., 1994).

    6.2  Human exposure

    6.2.1  Oral exposure

           2-Furaldehyde has been identified but not quantified as a major
    flavour component in a range of food items, including beef, soy sauce,
    roasted nuts, fried bacon, nectarines, baked potatoes, clove oil,
    preserved mangoes, rum, roasted coffee, and blue cheese (HSDB, 1998).
    Levels reported in food are as follows: non-alcoholic beverages, 4
    mg/litre; alcoholic beverages, 10 mg/litre; ice creams, ices, etc., 13
    mg/kg; candy, 12 mg/kg; baked goods (unspecified), 17 mg/kg; gelatins
    and puddings, 0.8 mg/kg; chewing gum, 45 mg/kg; and syrups, 30
    mg/litre (HSDB, 1998). 2-Furaldehyde was qualitatively identified in
    two out of eight samples of mothers' milk from urban sites in the USA

    (Pellizzari et al., 1982). Qualitative identification of 2-furaldehyde
    in drinking-water has been reported from both the USA and Europe; no
    quantification was reported (Kool et al., 1982).

    6.2.2  Inhalation exposure

           The remainder of the human exposure data available to the authors
    of this CICAD are restricted to the occupational environment.

           Measured inhalation exposure information was provided to the
    United Kingdom's Health and Safety Executive by the petrochemical
    industry. The Health and Safety Executive's National Exposure Data
    Base contains information on exposure for the use of 2-furaldehyde in
    the refractory industry and for a number of miscellaneous processes.
    In all the exposure groupings below, when routine and breakdown
    maintenance takes place and significant exposure to airborne
    2-furaldehyde is anticipated, it is expected that appropriate
    respiratory protective equipment would be used to minimize inhalation

           Exposures in the petrochemicals, resin and polymer manufacture,
    and distillation industries are likely to be very similar. EASE
    (Version 2) predictions seem to be in accord with the limited amount
    of measured exposure information provided by the petrochemicals
    industry (Gregg et al., 1997). The EASE predictions indicate that 8-h
    TWA exposures will be somewhat below 8 mg/m3 (2 ppm). There is
    insufficient information to predict 15-min TWA exposures for these

           Exposures in the refractories and abrasive wheels manufacturing
    industries are likely to be very similar. The high exposures measured
    by the Health and Safety Executive in the refractories industry (20%
    of 8-h TWA exposures are greater than 40 mg/m3 [10 ppm]) are likely
    to be reduced following advice given about the application of
    efficient local exhaust ventilation and the enclosure of the process
    where possible (Gregg et al., 1997). The EASE-predicted 8-h TWA
    exposures likely to result from these improvements will be between 2
    and 12 mg/m3 (0.5 and 3 ppm) (Gregg et al., 1997). There is every
    likelihood that exposures will actually be at the lower end of the
    range -- i.e., less than 8 mg/m3 (2 ppm). There is insufficient
    information to predict 15-min TWA exposures for these industries.

           In the flavouring industry, very little 2-furaldehyde appears to
    be used. The EASE model predicts exposures to be low: the 15-min TWA
    exposure is between 1.2 and 6.8 mg/m3 (0.3 and 1.7 ppm), and the 8-h
    TWA is between 0.04 and 0.2 mg/m3 (0.01 and 0.05 ppm) (Gregg et al.,

           For oilseed residue application, no personal exposure was
    detected. The extent of this industry is not known, but it seems that
    8-h exposures to 2-furaldehyde are likely to be well below 8 mg/m3
    (2 ppm) (Gregg et al., 1997). No comment can be made upon likely
    short-term exposures.

           Little is known about the extent of the use of 2-furaldehyde in
    the glass reinforced plastics industry. It is very likely that the
    application of appropriate controls would result in 8-h TWA exposures
    to 2-furaldehyde being reduced to below 8 mg/m3 (2 ppm) (Gregg et
    al., 1997). No comment can be made upon possible short-term exposures.

    6.2.3  Dermal exposure

           The industrial processes can be grouped in a similar manner to
    that adopted for the general discussion of inhalation exposure above
    (section 6.2.2). These predictions do not take account of personal
    protective equipment that may be worn. Such equipment may
    significantly reduce dermal exposure.

           The EASE-predicted dermal exposures for the petrochemicals, resin
    and polymer manufacture, and distillation industries are similar
    -- namely, between 0.1 and 1 mg/cm2 per day (Gregg et al., 1997).

           For the refractories and abrasive wheels manufacturing
    industries, the EASE-predicted dermal exposures are between 1 and 5
    mg/cm2 per day (Gregg et al., 1997). If improvements are made to the
    process containment, opportunities for dermal contact will be reduced,
    and predicted exposures will be reduced to between 0.1 and 1 mg/cm2
    per day.

           For the use of 2-furaldehyde in the flavourings industry, the
    EASE prediction for dermal exposure is between 0 and 0.1 mg/cm2 per
    day (Gregg et al., 1997). Insufficient information is provided for the
    other minor uses to make predictions of dermal exposure.


           No animal studies are available examining the toxicokinetics of
    2-furaldehyde by the inhalation or dermal routes; however, signs of
    systemic toxicity observed in animal studies (see section 8) indicate
    that 2-furaldehyde is readily absorbed via both these routes of

           Animal studies demonstrate that, following oral administration in
    rats, 2-furaldehyde is readily absorbed and rapidly excreted, with up
    to 85% of the administered dose being detected in the urine within 24
    h (Nomier et al., 1992). Some elimination via exhaled carbon dioxide
    (7% of dose) also occurs. Metabolism is characterized by oxidation or
    acetylation of the aldehyde group, followed by glycine conjugation.
    2-Furoylglycine is the major urinary metabolite, accounting for
    approximately 80% of the administered dose (Laham & Potvin, 1989;
    Nomier et al., 1992; Parkash & Caldwell, 1994). Other minor
    metabolites include furoic acid, furanacrylic acid, and furanacryluric

           In humans, absorption of the vapour via both the lungs and skin
    has been demonstrated (Flek & Sedivec, 1978a,b). Metabolism appears
    similar to that in rats, with the majority of the retained dose being
    excreted as urinary 2-furoylglycine. Furoic acid and furanacryluric
    acid are also detected as minor metabolites. Dermal absorption from
    liquid 2-furaldehyde has also been observed.


    8.1  Single exposure

           Unpublished or briefly reported papers indicate 1-, 4-, and 6-h
    inhalation LC50 values in rats of 4148, 940, and 700 mg/m3 (1037,
    235, and 175 ppm), respectively (Woods & Seevers, 1956; Terrill et
    al., 1989). In contrast, an apparently well-conducted published study
    indicated a 1-h LC50 value in rats of 756 mg/m3 (189 ppm) (Gupta et
    al., 1991; Mishra et al., 1991). In the rat and other species,
    respiratory tract irritation and lung damage were consistently
    observed following inhalation exposure, with lung oedema and
    congestion being reported in one study in rats immediately after
    exposure to 380 mg/m3 (95 ppm) for 1 h. Oral LD50 values in rats
    were in close agreement, ranging from 122 to 158 mg/kg body weight
    (Woods & Seevers, 1955; SRI International, 1982). Toxic signs observed
    indicated central nervous system depressant effects, with convulsions
    also observed. The lungs also appeared to be a target organ via oral
    dosing. No reliable information was available for the dermal route of

    8.2  Irritation and sensitization

           No signs of skin irritation were noted in rabbits following a
    single application of liquid 2-furaldehyde for 12 h, although mild
    irritation was observed following a 48-h application (Woods & Seevers,
    1955). Intense but reversible skin irritation was reported in
    guinea-pigs after repeated application of undiluted liquid
    2-furaldehyde (Agakishiyev, 1989, 1990).

           A single instillation of liquid 2-furaldehyde produced gross
    corneal opacities in rabbits (Woods & Seevers, 1955). 2-Furaldehyde
    vapour produced eye irritation in several studies following repeated
    exposure in different species (Gardner, 1925; Feron et al., 1979;
    Gupta et al., 1991).

           No information is available on the ability of 2-furaldehyde to
    act as a skin or respiratory sensitizer.

    8.3  Short-term exposure

           The principal effects of repeated inhalation exposure were
    similar to those seen in single-exposure experiments. Groups of rats
    were exposed to 0 or 160 mg 2-furaldehyde/m3 (0 or 40 ppm) 1 h/day
    for 5, 15, or 30 days (Gupta et al., 1991; Mishra et al., 1991), and
    groups of rabbits were exposed to 208, 520, or 1040 mg/m3 (52, 130,
    or 260 ppm) 4 h/day, 5 days/week, for at least 60 exposures
    (Castellino et al., 1963). Respiratory irritation, hyperplasia and
    degeneration of the olfactory epithelium, and lung congestion, oedema,

    and inflammation were observed in rats following exposure to 160
    mg/m3 (40 ppm) (Gupta et al., 1991; Mishra et al., 1991) and in
    rabbits following exposure to 1040 mg/m3 (260 ppm) (Castellino et
    al., 1963). There was also evidence of kidney damage seen
    histopathologically and anaemia in rabbits following exposure to 520
    mg 2-furaldehyde/m3 (130 ppm). A NOAEL of 208 mg/m3 (52 ppm) was
    identified in rabbits; a NOAEL was not identified for rats.

    8.4  Long-term exposure

    8.4.1  Subchronic exposuren

           Groups of hamsters were exposed to 0, 80, 460, or 2208 mg/m3
    (0, 20, 115, or 552 ppm) 6 h/day, 5 days/week, for 13 weeks (Feron et
    al., 1979). Respiratory irritation, hyperplasia and degeneration of
    the olfactory epithelium, and lung congestion, oedema, and
    inflammation were observed in hamsters following exposure to 2208
    mg/m3 (552 ppm) (Feron et al., 1979). Slight atrophy and hyperplasia
    of the olfactory epithelium were also seen following exposure to 460
    mg/m3 (115 ppm). A NOAEL of 80 mg/m3 (20 ppm) was identified.

           Groups of 20 male and female rats received 0, 11, 22, 45, 90, or
    180 mg 2-furaldehyde/kg body weight per day by oral gavage, 
    5 days/week for 13 weeks (NTP, 1990). Mild to moderate centrilobular
    vacuolation of hepatocytes was observed among all treated groups,
    although there was no clear relationship between dose and incidence or
    severity of the observed effect.

           Groups of 20 male and 20 female mice received 0, 75, 150, 300,
    600, or 1200 mg 2-furaldehyde/kg body weight per day by oral gavage, 
    5 days/week for 13 weeks (NTP, 1990). Relative liver weights were
    increased in a dose-related manner in all treated groups.
    Centrilobular coagulative necrosis of hepatocytes was seen at
    150 mg/kg body weight per day or more, and mild mononuclear
    inflammatory cell infiltrate was seen in all treated groups.

    8.4.2  Chronic exposure and carcinogenicity

           No inhalation carcinogenicity studies in rats or mice were
    available. An inhalation study in hamsters showed no evidence that
    2-furaldehyde vapour had carcinogenic potential following 52 weeks'
    exposure to 1000-1600 mg/m3 (250-400 ppm), 7 h/day, 5 days/week, by
    this route (Feron & Kruysse, 1978). Nor was there any indication that
    2-furaldehyde was carcinogenic to hamsters after 36 weekly
    intratracheal instillations (Feron, 1972). However, both these studies
    are not satisfactory negative studies, owing to their limited

           In a gavage study, groups of 50 male and 50 female F344/N rats
    were treated with 0, 30, or 60 mg 2-furaldehyde/kg body weight per
    day, 5 days/week for 103 weeks (NTP, 1990). Animals were observed
    twice daily, weighed monthly, and subjected to a thorough gross and
    microscopic examination either at death or at the end of the study.
    Mortality in males was not significantly affected by 2-furaldehyde
    treatment throughout the study. Corresponding survival rates among
    females were 18/50, 32/50, and 28/50. However, 19 of the 22 top-dose
    deaths in females were attributed to accidental gavage errors. There
    were no differences in body weight between test and control animals
    throughout the study, and there were no treatment-related clinical
    signs of toxicity. The main non-neoplastic changes observed in test
    animals were minimal to mild centrilobular necrosis of the liver in
    male rats (3/50, 9/50, 12/50) and biliary dysplasia with fibrosis in
    two top-dose males.

           Two cases of cholangiocarcinoma were seen in two other top-dose
    males. The historical incidence of bile duct neoplasms in corn oil
    vehicle control male F344/N rats in this laboratory was reported to be
    3/2145 (0.1%). No other findings of biological significance were
    observed. Hence, in this study, treatment by gavage with 2-furaldehyde
    produced an increase in bile duct carcinoma in male rats only,
    although a valid assessment of the carcinogenicity of 2-furaldehyde in
    female rats cannot be made because of the low numbers of animals
    surviving to the end of the study. Also, the high incidence of
    accidental deaths casts doubt over the quality of the experimental

           Groups of 50 male and 50 female B6C3F1 mice were also dosed with
    0, 50, 100, or 175 mg 2-furaldehyde/kg body weight per day by gavage,
    5 days/week for 103 weeks, in the NTP study (NTP, 1990). Animals were
    observed twice daily, weighed monthly, and subjected to a thorough
    gross and microscopic examination either at death or at the end of the
    study. No significant differences in survival were observed between
    2-furaldehyde-treated and untreated animals throughout the study.
    There were no differences in body weight gain between test and control
    animals throughout the study, and there were no clinical signs of
    treatment-related toxicity.

           Non-neoplastic changes included chronic inflammation and
    multifocal green-brown, granular pigmentation of the subserosa of the
    liver in mid- and top-dose mice of each sex and forestomach
    hyperplasia in 2-furaldehyde-treated female mice only. The principal
    neoplastic changes observed were increases in hepatocellular adenomas
    and hepatocellular carcinomas in males (adenoma: 9/50 [18%], 13/50
    [26%], 11/49 [22%], 19/50 [38%]; carcinoma: 7/50 [14%], 12/50 [24%],
    6/49 [12%], 21/50 [42%]; in control, low-, mid-, and top-dose animals,
    respectively). Only adenomas were observed in females, the incidences
    being dose-related: 1/50 (2%), 3/50 (6%), 5/50 (10%), 8/50 (16%).
    Increases in adenomas and/or carcinomas were statistically significant

    only in the top-dose animals of both sexes. An increase in squamous
    cell papillomas of the forestomach was also seen in top-dose female
    mice, although this increase was not statistically significant (1/50
    [2%], 0/50 [0%], 1/50 [2%], 6/50 [12%] in control, low-, mid-, and
    top-dose animals). No other findings of biological significance were

           In an initiation/promotion study in mice using the dermal route,
    an increased incidence of skin tumours was seen when 2-furaldehyde was
    applied in combination with the promoting agent (5/20 compared with
    1/20 in controls that received the promoting agent in combination with
    dimethyl sulfoxide) (Miyakama et al., 1991). When 2-furaldehyde was
    applied in combination with acetone, no skin tumours were seen.

           Following the administration of an unstated amount of
    2-furaldehyde to rats for 5 months, evidence of pre-neoplastic changes
    (the formation of glutathione  S-transferase placental form, GST-P,
    foci) was seen in livers (Shimizu et al., 1989). Liver cirrhosis was
    observed in treated rats; overall, however, it is impossible to reach
    any conclusions about the possible mechanisms underlying cancer
    induction from this study (e.g., to what extent cell proliferation or
    direct mutagenicity may be involved in liver tumour formation).

    8.5  Genotoxicity and related end-points

           Experiments in cell-free systems have demonstrated that
    2-furaldehyde causes DNA damage (Hadi & Rehman, 1989). Although
    bacterial mutation studies with 2-furaldehyde have been largely
    negative, they have in general been inadequately reported (Zdzienicka
    & Tudek, 1978; McMahon et al., 1979; Loquet et al., 1981; Soska et
    al., 1981; Marnett et al., 1985; Mortelmans et al., 1986; Shinohara &
    Omura, 1986; Kim et al., 1987, 1988; Nakamura et al., 1987; Shane et
    al., 1988; Kato et al., 1989). However, 2-furaldehyde is clearly
    genotoxic in vitro in mammalian cell test systems, producing
    chromosomal aberrations, gene mutations, and sister chromatid
    exchanges (Stich et al., 1981; Gomez-Arroyo & Souza, 1985; McGregor et
    al., 1988; Nishi et al., 1989; NTP, 1990). In addition, one positive
    result and one negative result were obtained in  Drosophila tests
    (Woodruff et al., 1985; Rodriguez-Arnaiz et al., 1992).

           The genotoxic potential of 2-furaldehyde  in vivo is less
    certain, with positive results being claimed in a briefly reported
    cytogenetics study and negative results being reported in another
    cytogenetics study and a sister chromatid exchange study (Subramanyam
    et al., 1989; NTP, 1990). Further details of these studies are
    provided in the source document to this CICAD (Gregg et al., 1997).
    Overall, no firm conclusions can be drawn from these reports.

           Point mutations in K-ras and H-ras genes were seen in the
    2-furaldehyde-treated mouse livers taken from the NTP carcinogenicity
    assay, demonstrating genotoxicity (possibly direct) at the tumour site
    (Reynolds et al., 1987).

    8.6  Reproductive and developmental toxicity

           No studies specifically addressing these end-points are

    8.7  Immunological and neurological effects

           No studies specifically addressing these end-points are


           The only effects reported following single exposure in humans
    relate to irritation. Throat and eye irritation was apparently
    experienced by a small group of workers exposed to 200 mg/m3 (50 ppm)
    for at least 12 min.1 Apparently no irritation was noted with
    40 mg/m3 (10 ppm) for 8 h or 80 mg/m3 (20 ppm) for 4 h.

           An unknown volume of 50% liquid 2-furaldehyde did not produce
    skin irritation in workers (Nazyrov & Yampol'skaya, 1969).
    Insufficient information is available on the ability of 2-furaldehyde
    to act as a skin or respiratory sensitizer in humans.

           A limited number of studies have investigated the effects of
    repeated occupational exposure to 2-furaldehyde. One study suggested
    that 2-furaldehyde led to eye, nose, and throat irritation in
    situations where 10-min average 2-furaldehyde concentrations of 12-64
    mg/m3 (3-16 ppm) were measured (Apol & Lucas, 1975). However, other
    substances, including creosote and liquid resins, may have contributed
    to the effects, and no firm conclusions with respect to the role of
    2-furaldehyde can be drawn. In another study, no evidence of
    respiratory effects in 2-furaldehyde-exposed workers was noted when
    the highest average concentration was given as around 8 mg/m3 (2 ppm)
    (Pawlowicz et al., 1984). However, no duration for this level of
    exposure and no indication of peak concentrations were presented. No
    conclusions can be drawn from other studies because of poor reporting
    of exposure to 2-furaldehyde or because of the potential for
    confounding factors to influence the findings.

           No information was available on carcinogenicity in humans. The
    only genotoxicity information available in humans comes from an
    inadequate study that did not demonstrate any significant increase in
    the incidence of sister chromatid exchanges in a group of only six
    employees potentially exposed to unknown concentrations of
    2-furaldehyde (Gomez-Arroyo & Souza, 1985).

           No information is available on reproductive toxicity in humans.


    1  QO Chemicals Inc. (1981) Summary of sensory response
       criteria, furfural in air concentrations, Table 3.
       Unpublished data.


    10.1  Aquatic organisms

           Results of acute toxicity tests on aquatic organisms are
    summarized in Table 2. All concentrations are nominal.

    10.2  Terrestrial organisms

           An estimated oral LD50 value of >98 mg/kg body weight has been
    reported for the red-winged blackbird ( Agelaius phoeniceus)
    (Schafer et al., 1983).


    11.1  Evaluation of health effects

    11.1.1  Hazard identification and dose-response assessment

           Acute toxicity data from animals are variable; overall, however,
    2-furaldehyde is toxic by the inhalation and oral routes (4-h LC50,
    940 mg/m3 [235 ppm]; oral LD50, about 120 mg/kg body weight), with
    no clear information in relation to the dermal route.

           Human data on effects of 2-furaldehyde are extremely limited and
    of poor quality, although mucous membrane irritation has been
    identified as the principal effect following exposure to
    concentrations apparently as low as 12 mg/m3 (3 ppm) (10-min
    average). However, peak exposure concentrations were not given, and
    co-exposure with other substances was possible. In another study,
    exposure to 40 mg/m3 (10 ppm) for 8 h or 80 mg/m3 (20 ppm) for 4 h
    apparently did not cause throat or eye irritancy.

           From repeated-inhalation exposure studies in animals, the main
    non-neoplastic effects are toxicity to the lung and respiratory tract.
    NOAELs of 80 and 208 mg/m3 (20 and 52 ppm) have been identified in
    hamsters and rabbits, respectively, from studies of up to 4-6 h/day, 5
    days/week, for 13 weeks. Chronic oral exposure to 2-furaldehyde
    produced increased incidences of bile duct carcinomas in male rats,
    malignant and benign tumours in the liver in male mice, and benign
    tumours in the liver and forestomach in female mice. The development
    of the liver and forestomach tumours may be related to the chronic
    inflammatory effects noted at the same organ sites.

           The results of mutagenicity tests with bacteria were largely
    negative, although 2-furaldehyde is clearly genotoxic  in vitro in
    mammalian cells, producing chromosomal aberrations, gene mutations,
    and sister chromatid exchanges.  In vivo genotoxicity has not been
    adequately studied, and no firm conclusions can be drawn.

           There are no adequate data available regarding reproductive or
    developmental effects; hence, it is not possible to evaluate the risk
    to human health for these end-points.

    11.1.2  Criteria for setting guidance values for 2-furaldehyde

           2-Furaldehyde vapour and liquid are readily absorbed through the
    skin, and experiments suggest that skin absorption of vapour may
    account for a significant proportion of the total body burden. In view
    of the potential for skin absorption, biological monitoring is an
    important aspect of occupational exposure assessment. This is achieved
    by measuring 2-furoic acid (after alkaline hydrolysis of the
    metabolite furoylglycine) in urine.

        Table 2: Acute toxicity of 2-furaldehyde to aquatic organisms.

    Organism                         End-point                             Concentration           Reference

    Bacteria and cyanobacteria

    Pseudomonas putida               Toxic threshold (16-h EC3, growth)    16                      Bringmann & Kuhn (1976)

    Microcystis aeruginosa           Toxic threshold (8-day EC5, growth)   2.7                     Bringmann & Kuhn (1976)


    Saccharomyces cerevisiae         EC14, growth                          1                       Banerjee et al. (1981)


    Scenedesmus quadricaudata        Toxic threshold (7-day EC3, growth)   31                      Bringmann & Kuhn (1980a)


    Entosiphon sulcatum              Toxic threshold (72-h EC5, growth)    0.6                     Bringmann & Kuhn (1980a)

    Uronema parduczi                 Toxic threshold (growth)              11                      Bringmann & Kuhn (1980b)

    Chilomonas paramaecium           Toxic threshold (48-h EC5, growth)    3.9                     Bringmann & Kuhn (1980c)


    Mosquito fish                    96-h LC50                             2410                    Wallen et al. (1957)
    Gambusia affinis                 NOEC

    Bluegill sunfish                 96-h LC50                             16                      Turnbull et al. (1954)
    Lepomis macrochirus

    Fathead minnow                   96-h LC50                             32                      Mattson et al. (1976)
    Pimephales promelas

    a ECn is the effective concentration inhibiting the stated end-point (growth) by n%.

           The relative importance of genotoxicity and chronic inflammation
    in tumorigenesis is uncertain; because of this uncertainty, it is not
    possible to reliably identify a threshold below which exposure to
    2-furaldehyde would not result in some risk to human health.

           The lack of available data to serve as a basis for estimation of
    indirect exposure of individuals to 2-furaldehyde from the general
    environment precludes the characterization of potential cancer risks
    for the general population.

    11.1.3  Sample risk characterization

           It is recognized that there are a number of different approaches
    to assessing the risks to human health posed by genotoxic and
    carcinogenic substances. In some jurisdictions, there are a number of
    models for characterizing potency, which may be of some benefit in
    priority-setting schemes.

           The scenario chosen here as an example is occupational exposure
    in the United Kingdom. With respect to the irritant effects, in
    general, in the industries where 2-furaldehyde is used, the measured
    and predicted (using EASE modelling) exposure concentrations indicate
    that there is little risk that irritation to the respiratory tract or
    eyes will occur. However, in the manufacture of refractories and
    abrasive wheels, current exposures in some parts of these industries
    give rise to concern that there would be the risk of developing
    irritation. Given the eye irritation potential of 2-furaldehyde, there
    is a risk of developing eye irritation if appropriate personal
    protective equipment is not employed to prevent eye contact with the

           With respect to the risk of genotoxicity and carcinogenicity, the
    picture is unclear. Although the measured and predicted levels of
    exposure to 2-furaldehyde generally are relatively low in these
    industries, the risk of developing genetic damage at sites of initial
    contact cannot be discounted, and thus there is cause for concern that
    this may occur. The relative importance of genotoxicity and chronic
    inflammation in tumorigenesis is uncertain, and a NOAEL cannot be
    reliably identified because of this uncertainty. Consequently, it is
    concluded that because of this toxicological picture, it is not
    possible to identify a level of exposure at which one could be certain
    that genetic damage leading to tumour formation would not occur; thus,
    under contemporary occupational exposure conditions, there is cause
    for concern for genotoxicity and carcinogenicity, although it is not
    possible to reliably quantify this.

           In view of the irritative effects reported in workers
    occupationally exposed to low exposure concentrations of
    2-furaldehyde, a short-term limit is likely to be appropriate in
    addition to the 8-h TWA.

    11.2  Evaluation of environmental effects

           Although some emission to the atmosphere is expected from wood
    burning, no atmospheric effects are expected given the short half-life
    for reaction with hydroxyl and other radicals and possible
    photodegradation of 2-furaldehyde. The low volatilization of the
    compound from water and soil would not be expected to add
    significantly to atmospheric levels.

           The majority of 2-furaldehyde released to the environment will be
    released to surface waters. Release from the wood pulp industry seems
    to be the major source.

           2-Furaldehyde has a low capacity for bioaccumulation. Binding to
    particulates in soil and aquatic sediment is expected to be very low,
    making 2-furaldehyde mobile in the environment.

           2-Furaldehyde is readily biodegraded in aerobic sewage sludge and
    has also been shown to degrade in anaerobic systems. Acclimation of
    the sludge improves degradation. The compound is toxic to anaerobic
    degrading bacteria at concentrations above 1000 mg/litre in
    unacclimated sludges (these concentrations have been reported in wood
    pulp waste), although acclimation allows full degradation at these

           LC50s in fish range from 16 to 32 mg/litre, with a reported NOEC
    in an acute test of 10 mg/litre. There are no test results for aquatic
    invertebrates. Toxic thresholds (EC3 to EC5 for cell multiplication)
    for bacteria, cyanobacteria, algae, and protozoa range from 0.6 to 31

           Only one estimated toxicity value is available for terrestrial
    organisms, and little emission to land is expected; on this basis, no
    quantitative risk assessment can be attempted for the terrestrial

    11.2.1  Predicted environmental concentration

           Very limited monitoring studies are available for surface waters,
    with only two isolated measurements at 2 µg/litre reported. The sample
    risk assessment will be based on emissions from the wood pulp
    industry, the expected worst case. Reported concentrations in sulfite
    evaporator condensate range up to 1280 mg/litre, with average
    concentrations at 274 mg/litre in a more recent study. Since the
    evaporator condensate represents 15% of the total wastewater flow, the
    concentration in wastewater would be 41.1 mg/litre average.

           Based on the average concentration and mainly default values from
    the OECD Technical Guidance Manual, the initial concentration in
    rivers receiving treated wastewater would be as follows:

    PEClocal (water) =  Ceffluent/[(1 +  Kp(susp) ×  C(susp)) ×  D]


    *      PEClocal (water) is the predicted environmental concentration (g/litre)

    *       Ceffluent is the concentration of the chemical in the wastewater
           treatment plant effluent (g/litre), 

           calculated as  Ceffluent =  I × (100 -  P)/100,


            I    =      input concentration to the wastewater treatment plant
                       (0.041 g/litre)

            P    =      percent removal in the wastewater treatment plant (91%,
                       based on the "ready biodegradability" of the compound)

    *       Kp(susp) is the suspended matter/water adsorption coefficient,
           calculated as  Kp(susp) =  foc(susp) ×  Koc, where:

            foc(susp) =      the fraction of organic carbon in suspended matter
                                (default 0.1)

            Koc       =      the organic carbon/water partition coefficient
                                (1.05; see section 5)

    *       C(susp) is the concentration of suspended matter in the river
           water in kg/litre (default concentration 15 mg/litre)

    *       D is the dilution factor for river flow (taken as 1000 minimum,
           as the wood pulp process requires large water input and as plants
           will normally be sited on moderate to large rivers)

           Under these conservative conditions, PEClocal(water) = 3.7 µg/litre.

    11.2.2  Predicted no-effect concentration

           As no test results are available for aquatic invertebrates and no
    long-term test results are available, an uncertainty factor of 1000
    will be applied to the lowest reported acute LC50 of 16 mg/litre for
    the bluegill sunfish ( Lepomis macrochirus) to give a predicted
    no-effect concentration (PNEC) of 16 µg/litre. It is not considered
    justifiable to base the PNEC on toxic threshold values.

    11.2.3  Environmental risk factors

           The risk factor (PEC/PNEC ratio) for aquatic organisms is,
    therefore, 0.23, indicating low risk. The distribution of reported
    toxicity test results against the worst-case PEC is plotted in Figure
    1, illustrating the safety margin.




           The International Agency for Research on Cancer concluded that
    "There is inadequate evidence in humans for the carcinogenicity of
    2-furaldehyde" and that "There is limited evidence in experimental
    animals for the carcinogenicity of 2-furaldehyde." Its overall
    evaluation is that "2-Furaldehyde is not classifiable as to its
    carcinogenicity to humans" (IARC, 1995).

           2-Furaldehyde has previously been evaluated by the Joint Expert
    Committee on Food Additives (JECFA, 1999), whose conclusions are
    summarized as follows:

           Because of concern about the tumours observed in male mice given
           furfural and the fact that no NOEL [no-observed-effect level] was
           identified for hepatotoxicity in rats, the Committee was unable
           to allocate an ADI [acceptable daily intake]. Before reviewing
           the substance again, the Committee would wish to review the
           results of studies of DNA binding in mice and of a 90-day study
           of toxicity in rats to identify a NOEL for hepatotoxicity.


           Human health hazards, together with preventive and protective
    measures and first aid recommendations, are presented in the
    International Chemical Safety Card (ICSC 0276) reproduced in this

    13.1  Health surveillance advice

           An exposure surveillance program could include monitoring of
    2-furoic acid in urine after alkaline hydrolysis of the main
    metabolite of 2-furaldehyde, furoylglycine, immediately following

    13.2  Advice to physicians

           In case of poisoning, treatment is supportive.

    13.3  Spillage

           In the event of spillage, measures should be undertaken to
    prevent this chemical from mixing with acids, bases, or oxidants
    because of the risk of fire or explosion.


           Information on national regulations, guidelines, and standards is
    available from the International Register of Potentially Toxic
    Chemicals (IRPTC) legal file.

           The reader should be aware that regulatory decisions about
    chemicals, taken in a certain country, can be fully understood only in
    the framework of the legislation of that country. The regulations and
    guidelines of all countries are subject to change and should always be
    verified with appropriate regulatory authorities before application.                            

    FURFURAL                                                                                   ICSC: 0276
                                                                                               November 1998
    CAS #         98-01-1                            2-Furancarboxyaldehyde
    RTECS #       LT7000000                            2-Furaldehyde
    UN #          1199                                2-Furylmethanal
    EC #          605-010-00-4                       C5H4O2/C4H3OCHO
                                                      Molecular mass: 96.1
    TYPES OF HAZARD         ACUTE HAZARDS/                    PREVENTION                        FIRST AID/FIRE 
    /EXPOSURE               SYMPTOMS                                                            FIGHTING
    FIRE                    Combustible.                      NO open flames.                   Powder, alcohol-resistant foam, 
                                                                                                                                           water spray, carbon dioxide.
    EXPLOSION               Above 60°C explosive vapour/air   Above 60°C use a dosed system,
                            mixtures may be formed.           ventilation, and explosion-proof
                                                              electrical equipment.
    Inhalation              Cough. Headache. Laboured         Ventilation, local exhaust, or    Fresh air, rest. Refer for
                            breathing. Shortness of breath.   breathing protection.             medical attention.
                            Sore throat.
    Skin                    MAY BE ABSORBED! Dry skin.        Protective clothing.              Remove contaminated clothes.
                            Redness. Pain.                                                      Rinse skin with plenty of water
                                                                                                or shower. Refer for
                                                                                                medical attention.
    Eyes                    Redness. Pain.                    Face shield.                      First rinse with plenty of water 
                                                                                                for several minutes (remove contact
                                                                                                lenses if easily
                                                                                                possible), then take to a doctor.
    Ingestion               Abdominal pain. Diarrhoea.        Do not eat, drink, or smoke       Rinse mouth. Give plenty of water 
                            Headache. Sore throat.            during work.                      to drink. Refer for medical attention.

    SPILLAGE DISPOSAL                                                            PACKAGING & LABELLING
    Collect leaking liquid in sealable                                           Do not transport with food and feedstuffs.
    containers. Absorb remaining liquid in                                       EU Classification
    sand or inert absorbent and remove to safe place.                            Symbol: T
    Do NOT let this chemical enter the environment.                              R: 21-23/25-36137-40
    (Extra personal protection: self-contained                                   S: (1/2-)26-36137/39-45
    breathing apparatus).                                                        UN Classification
                                                                                 UN Hazard Class: 6.1
                                                                                 UN Subsidiary Risks: 3
                                                                                 UN Pack Group: II


    EMERGENCY RESPONSE                                                           STORAGE
    Transport Emergency Card: TEC (R)-84                                         Separated from strong bases, strong acids,
    NFPA Code: H2; F2; R0;                                                       strong oxidants, food and feedstuffs. Keep
                                                                                 in the dark. Well closed. Ventilation
                                                                                 along the floor.
    PHYSICAL STATE; APPEARANCE:                                                  ROUTES OF EXPOSURE:

    COLOURLESS TO YELLOW LIQUID, WITH CHARACTERISTIC                             The substance can be absorbed Into the body 
    ODOUR. TURNS RED-BROWN ON EXPOSURE TO AIR AND                                by inhalation, through the skin and by 
    LIGHT.                                                                       ingestion.

    PHYSICAL DANGERS:                                                            EFFECTS OF SHORT-TERM EXPOSURE:

    The vapour is heavier than air.                                              The substance irritates the eyes, the skin
                                                                                 and the respiratory tract.

    CHEMICAL DANGERS:                                                            EFFECTS OF LONG-TERM OR REPEATED EXPOSURE:

    The substance polymerizes under the                                          The liquid defats the skin. The substance may
    influence of acids) or base(s)                                               have effects on the liver.
    with fire or explosion hazard. Reacts
    violently with oxidants. Attacks
    many plastics.


    TLV (as TWA): 2 ppm; 7.9 mg/m3 (skin) (ACGIH 1998).
                                                     PHYSICAL PROPERTIES
    Boiling point: 162°C                                                         Explosive limits, vol% in air: 2.1-19.3
    Melting point: -36.5°C                                                       Octanol/water partition coefficient as log Pow: 0.41
    Relative density (water = 1): 1.16
    Solubility In water, g/100 ml at 20°C: 8.3
    Vapour pressure, kPa at 20°C: 0.144
    Relative vapour density (air = 1): 3.31
    Flash point: 60°C (c.c.)
    Auto-ignition temperature: 315°C
                                                      ENVIRONMENTAL DATA
    This substance may be hazardous to the environment; special attention should be given to water organisms.
    The odour warning when the exposure limit value is exceeded is insufficient.
                                                     ADDITIONAL INFORMATION

    LEGAL NOTICE     Neither the CEC nor the IPCS nor any person acting on behalf of the CEC or the IPCS is responsible for the use
                     which might be made of this information
    (c) IPCS, CEC 1999


    Agakishiyev D (1989) Skin irritation of laboratory animals caused by
    single and combined applications of petroleum refinery (furfural and
    D-11 mineral oil distillate).  Vestnik Dermatologii i Venerologii,
    65:51-56 (HSE Translation No. 14358A).

    Agakishiyev D (1990) Changes in guinea-pig skin and visceral
    morphology after multiple epicutaneous exposure to furfural and D-11
    mineral oil distillate and to a combination of the two.  Vestnik
     Dermatologii i Venerologii, 66(12):16-20 (HSE Translation No.

    Apol A, Lucas J (1975)  Health hazard evaluation/toxicity
    determination  report, Pacific Grinding Wheel Co., Marysville,
    Washington. Cincinnati, OH, US Department of Health, Education and
    Welfare, National Institute for Occupational Safety and Health (Report
    No. 73-18-171).

    Banerjee N, Bhatnagar R, Viswanathan L (1981) Inhibition of glycolysis
    by furfural in  Saccharomyces cerevisiae. European journal of applied
     microbiology and biotechnology, 11:226-228.

    Belay N, Boopathy R, Voskuilen G (1997) Anaerobic transformation of
    furfural by  Methanococcus deltae. Applied environmental
    microbiology, 63:2092-2094.

    Benjamin M, Woods S, Ferguson J (1984) Anaerobic toxicity and
    biodegradability of pulp mill waste constituents.  Water research,

    Bringmann G, Kuhn R (1976) Vergleichende Befunde der Schadwirkung
    wassergefahrdender Stoffe gegen Bakterien ( Pseudomonas putida) und
    Blaualgen ( Microcystis aeruginosa).  GasWasserfach-Wasser Abwasser,

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

    Bringmann G, Kuhn R (1980b) Bestimmung der biologischen Schadwirkung
    wassergefahrdender Stoffe gegen Protozoen II Backterienfressende
    Ciliaten.  Zeitschrift fuer Wasser und Abwasser Forschung, 13:26-31.

    Bringmann G, Kuhn R (1980c) Bestimmung der biologischen Schadwirkung
    wassergefahrdender Stoffe gegen Protozoen III Saprozoische
    Flagellaten.  Zeitschrift fuer Wasser und Abwasser Forschung,

    Brune G, Schoberth S, Sahm H (1983) Growth of a strictly anaerobic
    bacterium on furfural (2-furaldehyde).  Applied environmental
     microbiology, 46:1187-1192.

    Carter W, Winer A, Pitts J (1981) Effect of peroxyacetyl nitrate on
    the initiation of photochemical smog.  Environmental science and
     technology, 15:829-831.

    Castellino N, Elmino O, Rozera G (1963) Experimental research on
    toxicity of furfural.  Archives of environmental health, 7:574-582.

    Dunlop AP, Peters FN (1953)  The furans. New York, NY, Reinhold
    Publishing Corporation (American Chemical Society Monograph Series
    Vol. 119).

    Espinosa-Mansilla A, Muno de la Pena A, Salinas F (1993) Semiautomatic
    determination of furanic aldehydes in food and pharmaceutical samples
    by a stopped-flow injection analysis method.  Journal of the
     Association of Official Analytical Chemists International,

    Ettinger M et al. (1954) In:  Proceedings of the 8th Industrial Waste
     Conference, Purdue University, West Lafayette, IN [cited in HSDB,

    Feron V (1972) Respiratory tract tumours in hamsters after
    intratracheal instillations of benzo(a)pyrene alone and with furfural.
     Cancer research, 32:28-36.

    Feron V, Kruysse A (1978) Effects of exposure to furfural vapour in
    hamsters simultaneously treated with benzo(a)pyrene or
    diethylnitrosamine.  Toxicology, 11:127-144.

    Feron V, Kruysse A, Dreef-van-der-Meulen H (1979) Repeated exposure to
    furfural vapour: 13 week study in Syrian golden hamsters.
     Zentralblatt fuer  Bakteriologie, Parasitenkunde,
     Infektionskrankheiten und Hygiene, Abteilung 1, Originale, Reihe B,

    Flek J, Sedivec V (1978a) Absorption, metabolism and excretion of
    furfural in man.  Prac-Lek, 30 (5):172-177 (HSE Translation No. 143

    Flek J, Sedivec V (l978b) Absorption, metabolism and excretion of
    furfural in man.  International archives of occupational and
     environmental health, 41:159-168.

    Gardner H (1925)  Physiological effects of vapours from a few
     solvents  used in paints, varnishes and lacquers. Scientific
    Section, Educational Bureau, Paint Manufacturers' Association of the
    U.S. (Circulation No. 250).

    Gomez-Arroyo S, Souza V (1985)  In vitro and occupational induction
    of SCE in human lymphocytes with furfuryl alcohol and furfural.
     Mutation research, 156:233-238.

    Gregg C, Rajan R, Cocker J, Groves J (1997)  2-Furaldehyde. Sudbury,
    Suffolk, UK, HSE Books (Risk Assessment Document EH72/6; ISBN

    Gupta G, Mishra A, Agarwal D (1991) Inhalation toxicology of furfural
    vapours: an assessment of biochemical response in rat lungs.
     Journal of applied toxicology, 11:343-347.

    Hadi S, Rehman S (1989) Specificity of the interaction of furfural
    with DNA.  Mutation research, 225:101-106.

    Hampton C, Pierson W, Harvey T, Updegrove W, Marano R (1982)
    Hydrocarbon gases emitted from vehicles on the road. I. A qualitative
    gas-chromatography mass-spectrometry survey.  Environmental science
     and technology, 16:287-298.

    HSDB (1998)  Hazardous substances data bank. Published by Micromedex
    Inc. (Copyright 1998). Accessed via the CD-ROM version.

    IARC (1995) Dry cleaning, some chlorinated solvents and other
    industrial chemicals.  IARC monographs on the evaluation of
     carcinogenic risks to man, 63:409-429.

    IPCS (1993)  International Chemical Safety Card -- Furfural. Geneva,
    World Health Organization, International Programme on Chemical Safety
    (ICSC 0276).

    Japan Environment Agency (1998)  Chemicals in the environment, 1997
    ed. Tokyo, Japan Environment Agency, Environmental Health and Safety

    JECFA (1999)  Toxicological evaluation of certain food additives.
    Geneva, World Health Organization, International Programme on Chemical
    Safety, Joint FAO/WHO Expert Committee on Food Additives, pp. 33-56
    (WHO Food Additives Series 42). 

    Juttner F (1986) Analysis of organic-compounds (VOC) in the forest air
    of the southern Black Forest.  Chemosphere, 15:985-992.

    Karickhoff S, Brown D, Scott T (1979) Sorption of hydrophobic
    pollutants on natural sediments.  Water research, 13:241-248.

    Kato F, Araki A, Nozaki K, Matsushima T (1989) Mutagenicity of
    aldehydes and diketones.  Mutation research, 216:366-367.

    Kawasaki M (1980) Experiences with the test scheme under the Chemical
    Control Law of Japan: An approach to structure-activity correlations.
     Ecotoxicology and environmental safety, 4:444-454.

    Keith L (1974) Chemical characterization of industrial wastewaters by
    gas chromatography-mass spectrometry.  Science of the total
     environment, 3:87-102.

    Kim S, Hayase F, Kato H (1987) Desmutagenic effect of alpha-dicarbonyl
    and alpha-hydroxycarbonyl compounds against mutagenic heterocyclic
    amines.  Mutation research, 177:9-15.

    Kim S, Kim I, Yeum D, Park Y (1988) Desmutagenic action of sugar
    degradation products.  Korean journal of food science and technology,
    20 (1):119-124.

    Kim T, Hah Y, Hong S (1983) Toxic effects of furfural on
     Pseudomonas fluorescens. Korean journal of microbiology, 21:149-155.

    Kleindienst T, Shepson P, Edney E, Claxton L, Cupitt L (1986) Wood
    smoke -- measurement of the mutagenic activity of its gas-phase and
    particulate-phase photooxidation products.  Environmental science and
     technology, 20:493-501.

    Kool HJ, van Kreijl CF, Zoetman BCJ (1982) Toxicological assessment of
    organic compounds in drinking water.  Critical reviews in toxicology,

    Laham S, Potvin M (1989) Metabolism of furfural in the Sprague-Dawley
    rat.  Toxicology and environmental chemistry, 24:35-47.

    Lipari F, Dasch JM, Scruggs WF (1984) Aldehyde emissions from
    wood-burning fireplaces.  Environmental science and technology,

    Lo Coco F, Ceccon L, Valentini C, Novelli V (1992) High performance
    liquid chromatographic determination of 2-furaldehyde in spirits.
     Journal of chromatography, 590:235-240.

    Loquet C, Toussaint G, LeTalaer J (1981) Studies on mutagenic
    constituents of apple brandy and various alcoholic beverages collected
    in Western France, a high incidence area for oesophageal cancer.
     Mutation research, 88:155-164.

    Maga J (1979) Furans in foods. Critical review.  Food science and
     nutrition, 4:355-399.

    Marnett L, Hurd H, Hollstein M, Levin D, Esterbauer H, Ames B (1985)
    Naturally occurring carbonyl compounds are mutagens in  Salmonella
    tester strain TA 104.  Mutation research, 148:25-34.

    Mattson V, Arthur J, Walbridge C (1976)  Acute toxicity of selected
     organic compounds to fathead minnows. Duluth, MN, US Environment
    Protection Agency, Environmental Research Laboratory (Report No.

    McGregor D, Brown A, Cattanach P, Edwards I, McBride D, Caspary W
    (1988) Responses of the L5l78Y tk+/tk- mouse lymphoma cell forward
    mutation assay II: 18 coded chemicals.  Environmental molecular
     mutagenesis, 11:91-118.

    McMahon R, Cline J, Thompson C (1979) Assay of 855 test chemicals in
    ten tester strains using a new modification of the Ames test for
    bacterial mutagens.  Cancer research, 39:682-693.

    Mishra A, Dwivedi P, Verma A, Sinha M, Mishra J, Lal K, Pandya K,
    Dutta K (1991) Pathological and biochemical alterations induced by
    inhalation of furfural vapour in rat lung.  Bulletin of environmental
     contamination and toxicology, 47:668-674.

    Miyakama Y, Nishi Y, Kato K, Sato H, Takahashi M, Hayashi Y (1991)
    Initiating activity of eight pyrolysates of carbohydrates in a two
    stage mouse skin tumorigenesis model.  Carcinogenesis, 12:1169-1173.

    Mortelmans K, Haworth S, Lawlor T, Speck W, Tainer B, Zeiger E (1986)
     Salmonella mutagenicity tests 11: Results from the testing of 270
    chemicals.  Environmental mutagenesis, 8 (Suppl. 7):1-119.

    Nakamura S, Oda Y, Shimada T, Oki I, Sugimoto K (1987) SOS-inducing
    activity of chemical carcinogens and mutagens in  Salmonella
     typhimurium TA 1535/pSK1002. Examination of 151 chemicals.
     Mutation  research, 192:239-246.

    Nazyrov G, Yampol'skaya Y (1969) The effect of furan resins on the
    skin and skin allergies of persons employed in their manufacture.
     Trudy Institut Gigiena Truda i Professionalyne Zabolevaniya, 10:
    19-21 (HSE Translation No. 14480A).

    NIOSH (1987)  NIOSH Proficiency Analytical Testing (PAT) Program.
    Cincinnati, OH, US Department of Health, Education and Welfare,
    National Institute for Occupational Safety and Health (DHEW
    Publication No. 77-173).

    Nishi Y, Miyakama Y, Kato K (1989) Chromosome aberrations induced by
    pyrolysates of carbohydrates in Chinese hamster V79 cells.
     Mutation research, 227:117-123.

    Nomier A, Silveira D, McComish M, Chadwick M (1992) Comparative
    metabolism and disposition of furfural and furfural alcohol in rats.
     Drug metabolism and disposition, 20:198-204.

    NTP (1990)  Toxicology and carcinogenesis studies of furfural in
    F344/N  rats and B6C3F1 mice (gavage studies). Research Triangle
    Park, NC, US Department of Health and Human Services, Public Health
    Service, National Institutes of Health, National Toxicology Program
    (Technical Report Series No. 382; NIH Publication No. 90-2837).

    Nutley B (1989)  An analytical method for biological monitoring of
     furfural exposure. Sheffield, UK, Health and Safety Executive,
    Health and Safety Laboratories (Section Report IR/L/OT/89/1).

    Parkash M, Caldwell J (1994) Metabolism and excretion of
    [14C]furfural in the rat and mouse.  Food and chemical toxicology,

    Patel S, Robertson S, Brown R (1988) Method validation for atmospheric
    monitoring -- an illustration with furfural. In:  Proceedings of the
     Sixth Thermal Desorption Symposium, Anughaha, Windsor, UK.

    Pawlowicz A, Droszcz W, Garlicki A, Kutyla J, Kowalczyk M (1984)
    Effect of furfural on the respiratory system.  Medycyna Pracy,
    35:39-45 (HSE Translation No. 14361B).

    Pellizzari E, Hartwell T, Harris B, Waddell R, Whitaker D, Erickson M
    (1982) Purgeable organic compounds in mothers' milk.  Bulletin of
     environmental contamination and toxicology, 28:322-328.

    Pitter P (1976) Determination of biological degradability of organic
    substances.  Water research, 10:231-235.

    Reynolds S, Stower S, Patterson R, Maronpot R, Aaronson S, Anderson M
    (1987) Activated oncogenes in B6C3F1 mouse liver tumours:
    implications for risk assessment.  Science, 237:1309-1316. 

    Rodriguez-Arnaiz R, Morales P, Zimmering S (1992) Evaluation in
     Drosophila melanogaster of the mutagenic potential of furfural in
    the mei-9a test for chromosome loss in germ-line cells and the wing
    spot test for mutational activity in somatic cells. 
     Mutation research, 280:75-80.

    Rowe E, Tullos L (1980) Lube solvents no threat to waste treatment.
     Hydrocarbon processing, 59:63-65.

    Ruus L (1964) A study of waste waters from the forest products
    industry. 4. Composition of biochemical oxygen demand of condensate
    from spent sulfite liquor evaporation.  Svensk Papperstidning,

    Schafer E, Bowles W, Hurlbut J (1983) The acute oral toxicity,
    repellency and hazard potential of 998 chemicals to one or more
    species of wild and domestic birds.  Archives of environmental
     contamination and toxicology, 12:355-382.

    Sedivec V, Flek J (1978) Biologic monitoring of persons exposed to
    furfural vapours.  International archives of occupational and
     environmental health, 42:41-49.

    Shane B, Troxclair A, McMillin D, Henry C (1988) Comparative
    mutagenicity of 9 brands of coffee to  Salmonella typhimurium TA100,
    TA102, TA104.  Environmental molecular mutagenesis, 11:195-206.

    Shimizu A, Nakamura Y, Harada M, Ono T, Sato K, Inoue T, Kanisawa M
    (1989) Positive foci of glutathione  S-transferase placental form in
    the liver of rats given furfural by oral administration.
     Japanese journal of cancer research, 80:608-611.

    Shinohara K, Omura H (1986) Furans as mutagens formed by
    amino-carbonyl reactions.  Developmental food science, 3:353-362.

    Soska J, Koukalova B, Ebringer L (1981) Mutagenic activities of simple
    nitrofuran derivatives. Comparison of related compounds in the phage
    inductest, chloroplast-bleaching and bacterial-repair and mutagenicity
    tests.  Mutation research, 81:21-26.

    SRI International (1982)  The acute oral toxicity of furfural in
     various vehicles in the rat. Menlo Park, California (SRI Project No.
    LSC-4357; Compound Report No. 1, August 1982).

    Stich H, Rosin M, Wu C, Powrie W (1981) Clastogenicity of furans found
    in food.  Cancer letters, 13:89-95.

    Subramanyam S, Sailaja D, Rathnaprabha D (1989) Genotoxic assay of two
    dietary furans by some  in vivo cytogenetic parameters.
     Environmental molecular mutagenesis, 14 (Suppl. 15):239.

    Terrill J, Van Horn W, Robinson D, Thomas D (1989) Acute inhalation
    toxicity of furan, 2-methyl furan, furfuryl alcohol and furfural in
    the rat.  American Industrial Hygiene Association journal,

    Turnbull H, DeMann J, Weston R (1954) Toxicity of various refinery
    materials to fresh water fish.  Industrial and engineering chemistry,

    US EPA (1998) Toxic Substances Control Act: Inventory update rule 51.
    In:  Federal register. Washington, DC, US Environmental Protection

    Wallen I, Greer W, Lasater R (1957) Toxicity to  Gambusia affinis of
    certain pure chemicals in turbid waters.  Sewage and industrial
     wastes, 29:695-711.

    Wang P, Brenchley J, Humphrey A (1994) Screening microorganisms for
    utilization of furfural and possible intermediates in its degradation
    pathway.  Biotechnology letters, 16:977-982.

    Woodruff R, Mason J, Valencia R, Zimmering S (1985) Chemical
    mutagenesis testing in  Drosophila. V. Results of 53 coded compounds
    tested for the National Toxicology Program.  Environmental
    mutagenesis, 7:677-702. 

    Woods L, Seevers M (1955)  Toxicity of furfural. Unpublished report,
    University of Michigan Medical School, Ann Arbor, MI. 28 March 1955.

    Woods L, Seevers M (1956)  Toxicity of furfural. Unpublished report,
    University of Michigan Medical School, Ann Arbor, MI. February 1956.

    Zdzienicka M, Tudek B (1978) Mutagenic activity of furfural in
     Salmonella typhimurium TA 100.  Mutation research, 58:205-209.

    Zhang J, He Q, Lioy P (1994) Characteristics of aldehydes --
    concentrations, sources and exposures for indoor and outdoor
    residential microenvironments.  Environmental science and technology,


    Gregg et al. (1997):  2-Furaldehyde (Risk Assessment Document EH72/6)

           The authors' draft version of this Health and Safety Executive
    report was initially reviewed internally by a group of approximately
    10 Health and Safety Executive experts (mainly toxicologists, but also
    scientists from other relevant disciplines, such as epidemiology and
    occupational hygiene). The toxicology section of the amended draft was
    then reviewed by toxicologists from the United Kingdom Department of
    Health. Subsequently, the entire risk assessment document was reviewed
    by a tripartite advisory committee to the United Kingdom Health and
    Safety Commission, the Working Group for the Assessment of Toxic
    Chemicals (WATCH). This committee is composed of experts in toxicology
    and occupational health and hygiene from industry, trade unions, and

           The members of the WATCH committee at the time of the peer review
    were Mr Steve Bailey, Confederation of British Industries; Professor
    Jim Bridges, University of Surrey; Dr Ian Guest, Confederation of
    British Industries; Dr Alastair Hay, Trade Unions Congress; Dr Jenny
    Leeser, Confederation of British Industries; Dr Len Levy, Institute of
    Occupational Hygiene, Birmingham; Dr Mike Molyneux, Confederation of
    British Industries; Mr Alan Moses, Confederation of British
    Industries; Dr Ron Owen, Trade Unions Congress; Mr Jim Sanderson,
    Independent Consultant; and Dr Mike Sharratt, University of Surrey.


           The draft CICAD on 2-furaldehyde was sent for review to
    institutions and organizations identified by IPCS after contact with
    IPCS national Contact Points and Participating Institutions, as well
    as to identified experts. Comments were received from:

           Chinese Academy of Preventive Medicine, Ministry of Health,
           Beijing, People's Republic of China

           Federal Institute for Health Protection of Consumers & Veterinary
           Medicine, Berlin, Germany

           National Institute of Health Sciences, Tokyo, Japan

           National Institute of Public Health and Environmental Protection
           (RIVM), Bilthoven, The Netherlands

           Senatskommission der Deutschen Forschungsgemeinschaft, Bonn,

           United States Department of Health and Human Services (National
           Institute for Occupational Safety and Health, Cincinnati;
           National Institute of Environmental Health Sciences, Research
           Triangle Park), USA

           United States Environmental Protection Agency (Region VIII;
           National Center for Environmental Assessment, Washington, DC),

           World Health Organization/International Programme on Chemical
           Safety, Montreal, Canada


    Washington, DC, USA, 8-11 December 1998


    Dr T. Berzins, National Chemicals Inspectorate (KEMI), Solna, Sweden
    ( Vice-Chairperson)

    Mr R. Cary, Toxicology Unit, Health Directorate, Health and Safety
    Executive, Bootle, Merseyside, United Kingdom ( Rapporteur)

    Dr S. Dobson, Institute of Terrestrial Ecology, Monks Wood, Abbots
    Ripton, Huntingdon, Cambridgeshire, United Kingdom

    Dr O. Faroon, Agency for Toxic Substances and Disease Registry,
    Centers for Disease Control and Prevention, Atlanta, GA, USA

    Dr G. Foureman, National Center for Environmental Assessment, US
    Environmental Protection Agency, Research Triangle Park, NC, USA

    Dr H. Gibb, National Center for Environmental Assessment, US
    Environmental Protection Agency, Washington, DC, USA ( Chairperson)

    Dr R.F. Hertel, Federal Institute for Health Protection of Consumers &
    Veterinary Medicine, Berlin, Germany

    Dr I. Mangelsdorf, Documentation and Assessment of Chemicals,
    Fraunhofer Institute for Toxicology and Aerosol Research, Hanover,

    Dr A. Nishikawa, Division of Pathology, National Institute of Health
    Sciences, Tokyo, Japan

    Dr E.V. Ohanian, Office of Water/Office of Science and Technology,
    Health and Ecological Criteria Division, US Environmental Protection
    Agency, Washington, DC, USA

    Dr J. Sekizawa, Division of Chem-Bio Informatics, National Institute
    of Health Sciences, Tokyo, Japan

    Professor P. Yao, Institute of Occupational Medicine, Chinese Academy
    of Preventive Medicine, Ministry of Health, Beijing, People's Republic
    of China


    Dr K. Austin, National Center for Environmental Assessment, US
    Environmental Protection Agency, Washington, DC, USA

    Dr I. Daly (ICCA representative), Regulatory and Technical Associates,
    Lebanon, NJ, USA

    Ms K.L. Lang (CEFIC, European Chemical Industry Council,
    representative), Shell International, London, United Kingdom

    Ms K. Roberts (ICCA representative), Chemical Self-funded Technical
    Advocacy and Research (CHEMSTAR), Chemical Manufacturers Association,
    Arlington, VA, USA

    Dr W. Snellings (ICCA representative), Union Carbide Corporation,
    Danbury, CN, USA

    Dr M. Sweeney, Document Development Branch, National Institute for
    Occupational Safety and Health, Cincinnati, OH, USA 

    Dr K. Ziegler-Skylakakis, GSF-Forschungszentrum für Umwelt und
    Gesundheit GmbH, Institut für Toxikologie, Oberschleissheim, Germany


    Dr M. Baril, Institut de Recherches en Santé et Sécurité du Travail du
    Québec (IRSST), Montreal, Quebec, Canada

    Dr H. Galal-Gorchev, Chevy Chase, MD, USA

    Ms M. Godden, Health and Safety Executive, Bootle, Merseyside, United

    Dr R.G. Liteplo, Environmental Health Directorate, Health Canada,
    Ottawa, Ontario, Canada

    Ms L. Regis, Programme for the Promotion of Chemical Safety, World
    Health Organization, Geneva, Switzerland

    Mr A. Strawson, Health and Safety Executive, London, United Kingdom

    Dr P. Toft, Programme for the Promotion of Chemical Safety, World
    Health Organization, Geneva, Switzerland


           Ce CICAD relatif au 2-furaldéhyde est basé sur une mise au point
    rédigée par le Health and Safety Executive du Royaume-Uni au sujet des
    effets que ce composé pourrait avoir sur la santé humaine,
    principalement en milieu professionnel, mais aussi sur l'environnement
    en général (Gregg et al., 1997). Ce document est donc principalement
    consacré aux voies d'exposition qui existent sur lieux de travail,
    mais il comporte également une évaluation d'ordre écologique. Les
    données prises en compte vont jusqu'en janvier 1997. Une bibliographie
    complémentaire a été effectuée jusqu'à décembre 1997 afin de relever
    les données qui auraient pu être publiées après la première recherche
    bibliographique, mais sans résultat. On trouvera à l'appendice 1 des
    indications sur le mode d'examen par des pairs ainsi que sur les
    sources documentaires utilisées. Les renseignements concernant
    l'examen du CICAD par les pairs font l'objet de l'appendice 2. Ce
    CICAD a été approuvé en tant qu'évaluation internationale lors de la
    réunion du Comité d'évaluation finale qui s'est tenue à Washington du
    8 au 11 décembre 1998. La liste des participants à cette réunion
    figure à l'appendice 3. La fiche d'information internationale sur la
    sécurité chimique (ICSC No 0276) relative au 2-furaldéhyde, établie
    par le Programme internationale sur la sécurité chimique (IPCS, 1993),
    est également reproduite dans ce document.

           Le 2-furaldéhyde (C5H4O2) (No CAS 98-01-1) se présente sous la
    forme d'un liquide à l'odeur piquante, rappelant celle des amandes. On
    le trouve à l'état de traces dans diverses denrées alimentaires et il
    est produit industriellement par digestion en continu ou en discontinu
    des pentosanes contenus dans les déchets agricoles. Ces pentosanes
    sont hydrolysés en pentoses qui subissent ensuite une
    cyclodéshydratation en 2-furaldéhyde. On utilise ce composé dans
    l'industrie pour la production de résines, de meules et de substances
    réfractaires, pour le raffinage des huiles lubrifiantes et la
    récupération des solvants. On l'emploie également en très petites
    quantités comme aromatisant.

           Le 2-furaldéhyde est présent dans de nombreuses denrées
    alimentaires, soit naturellement soit comme contaminant. On en a
    signalé la présence dans l'eau destinée à la boisson et le lait
    maternel, mais en quantités non mesurables.

           On dispose de mesures portant sur l'exposition professionnelle
    par inhalation et des estimations ont été obtenues au moyen d'un
    système expert appelé Estimation and Assessment of Substance Exposure
    (EASE). En règle générale, dans l'ensemble des industries,
    l'exposition au 2-furaldéhyde présent dans l'air est inférieure à 8
    mg/m3 (2 ppm) en moyenne pondérée par rapport au temps calculée sur 8
    h (TWA). Pour la plupart des industries, cette donnée ne permet pas de

    prévoir l'exposition moyenne pondérée sur 15 minutes. Toutefois, on a
    calculé que dans l'industrie des aromatisants, l'exposition moyenne
    pondérée sur 15 min devait se situer entre 1,2 et 6,8 mg/m3
    (c'est-à-dire entre 0,3 et 1,7 ppm). On ne dispose d'aucune mesure de
    l'exposition par voie cutanée. Le système EASE donne une exposition
    cutanée comprise entre 0,1 et 1 mg/cm2 j-1 pour la plupart des
    industries, avec des valeurs plus élevées (entre 1 et 5 mg/cm2 j-1)
    dans la fabrication de matériaux abrasifs et de meules.

           Les données toxicocinétiques sont limitées, mais on est fondé à
    penser que le 2-furaldéhyde est facilement résorbé par la voie
    respiratoire et la voie percutanée. L'expérimentation animale montre
    qu'après administration par voie orale à des rats, le composé est
    facilement absorbé et rapidement excrété, principalement dans les
    urines, mais une petite partie passe également dans l'air expiré sous
    la forme de dioxyde de carbone. Le métabolisme du 2-furaldéhyde se
    caractérise par l'oxydation ou l'acétylation du groupement aldéhyde,
    suivie par une conjugaison avec la glycine. La 2-furoylglycine est le
    principal métabolite urinaire à côté de l'acide furoïque, de l'acide
    furanacrylique et de l'acide furanacrylurique, dont l'importance est

           Chez l'Homme, on a mis en évidence une résorption du
    2-furaldéhyde gazeux au niveau des poumons et de la peau. L'organisme
    humain métabolise ce composé de manière analogue à celui du rat, la
    majeure partie de la dose absorbée se retrouvant dans les urines sous
    la forme de 2-furoylglycine. L'acide furoïque et l'acide
    furanacrylurique sont également présents en moindre quantité. On
    observé une résorption du 2-furanaldéhyde par la voie percutanée.

           Chez l'animal, la toxicité aiguë du composé est variable :
    globalement, le 2-furaldéhyde est toxique par la voie respiratoire et
    la voie orale (CL50 à 4 h, 940 mg/m3 [235 ppm]; DL50 par voie orale,
    environ 120 mg/kg de poids corporel) et l'on ne possède pas de données
    claire au sujet de la voie percutanée. Après exposition unique ou
    répétée au produit par inhalation, on observe systématiquement une
    irritation des voies respiratoires et des lésions pulmonaires. On a
    également fait état d'irritation de la peau et des yeux. Il semble en
    revanche qu'on n'ait pas noté d'irritation de la gorge ou des yeux
    chez des sujets humains exposés à une concentration de 40 mg/m3 (10
    ppm) pendant 8 h ou de 80 mg/m3 pendant 4 h. Chez l'animal, on a
    obtenu, pour la dose sans effet nocif observable (NOAEL) relative aux
    effets cancérogènes, une valeur de 80 mg/m3 (20 ppm) dans le cas du
    hamster et de 208 mg/m3 (52 ppm) dans le cas du hamster, lors
    d'études qui se sont prolongées jusqu'à 13 semaines. Après avoir fait
    ingérer le composé à rats et des souris pendant 103 semaines, à des
    doses respectivement égales à 60 et 50 mg/kg de poids corporel, on a

    des tumeurs malignes et bénignes. Le 2-furaldéhyde est indéniablement
    génotoxique  in vitro sur des cultures de mammifères; on ne peut
    tirer de conclusions définitives quant à la génotoxicité de ce composé
     in vivo, mais on ne peut pas exclure non plus que cette génotoxicité
    soit réelle et qu'elle puisse contribuer au processus de
    cancérisation. Dans ces conditions, il n'est pas possible de
    déterminer avec certitude la valeur de la NOAEL.

           Faute de données utilisables pour l'estimation de l'exposition
    individuelle indirecte au 2-furaldéhyde présent dans l'environnement
    général, il est impossible de préciser le risque cancérogène que ce
    composé représente pour la population dans son ensemble.

           En milieu professionnel, il existe un risque d'effets
    cancérogènes et génotoxiques. Il y cependant incertitude quant au
    degré de risque; il est donc nécessaire de continuer à réduire
    l'exposition autant qu'il est techniquement possible de le faire.

           On ne dispose pas de données suffisantes concernant les effets du
    composé sur la reproduction et le développement; il n'est donc pas
    possible de déterminer s'il existe des risques de cette nature pour

           C'est l'industrie de la pâte à papier qui rejette le plus de
    2-furaldéhyde dans l'environnement. La combustion du bois, qu'elle
    soit naturelle ou d'origine humaine, entraîne également la libération
    de se composé dans l'atmosphère. 

           On ne prévoit pas d'effets atmosphériques étant donné que le
    2-furaldéhyde est détruit par réaction sur les radicaux hydroxyle, sa
    demi-vie calculée dans l'atmosphère étant égale à 0,44 jours. Dans
    l'air des villes, il peut également être décomposé par réaction avec
    des radicaux nitrate. Une photo-oxydation directe n'est pas non plus à
    exclure. Etant donné la faible valeur de la tension de vapeur et de la
    constante de Henry, sa volatilisation à partir de l'eau et du sol
    devrait être lente.

           Il ne devrait pas y avoir d'hydrolyse aux valeurs du pH
    rencontrées dans l'environnement. La faible valeur du coefficient de
    partage entre l'octanol et l'eau (log  Kow = 0,41) indique que la
    capacité de bioaccumulation est faible. Le coefficient de sorption
    ( Koc) montre que la fixation aux particules n'est pas importante et
    que le composé est par conséquent très mobile dans le sol.

           Le 2-furaldéhyde subit une biodégradation aérobie rapide dans les
    boues d'égout ainsi que dans les eaux superficielles. Cette
    décomposition se produit également en anaérobiose et de nombreuses
    bactéries et autres microorganismes sont capables d'utiliser ce
    composé comme seule source de carbone. A forte concentration (>1000
    mg/litre), le 2-furaldéhyde inhibe la croissance et l'activité

    métabolique des cultures anaérobies non adaptées. En revanche, le
    produit est plus facilement biodégradable par acclimatation des boues

           Les concentrations de 2-furaldéhyde les plus élevées qui aient
    été constatées dans des eaux résiduaires industrielles provenaient de
    condensats (environ 15 % des eaux résiduaires totales) rejetés par les
    évaporateurs à bisulfite d'une usine de pâte à papier, avec une
    moyenne de 274 mg/litre. On ne dispose que d'une seule étude donnant
    les résultats de dosages du 2-furaldéhyde dans l'air intérieur et
    extérieur; la valeur trouvée est d'environ 1 µg/m3; dans d'autres
    études, on a mis en évidence la présence du composé mais sans procéder
    à un dosage.

           Le seuil de toxicité pour divers microorganismes se situe entre
    0,6 et 31 mg/litre. Pour les poissons, la CL50 relative aux effets
    toxiques aigus est comprise entre 16 et 32 mg/litre.

           En se basant sur les concentrations auxquelles les rejets des
    usines de pâte à papier sont susceptibles de donner lieu dans
    l'environnement (cas le plus grave) et en prenant un facteur
    d'incertitude de 1000 pour tenir compte de ce que les données de
    toxicité aiguës sont limitées, on peut considérer que la libération de
    2-furaldéhyde dans l'environnement représente un danger pour les
    organismes aquatiques. On ne possède pas de données permettant
    d'évaluer le risque pour les organismes terrestres, mais en tout état
    de cause la décharge de 2-furaldéhyde au niveau du sol est
    vraisemblablement peu importante.


           El presente CICAD sobre el 2-furaldehído, preparado por la
    Dirección de Salud y Seguridad del Reino Unido (Gregg  et al., 1997),
    se basa en un examen de los problemas relativos a la salud humana
    (fundamentalmente ocupacionales), pero también contiene información
    ambiental. Por consiguiente, este documento se concentra sobre todo en
    la exposición a través de las rutas que son de interés para el entorno
    ocupacional, pero incluye también una evaluación ambiental. En este
    examen se han incorporado los datos identificados hasta enero de 1997.
    Se realizó una ulterior búsqueda bibliográfica hasta diciembre de 1997
    para localizar la nueva información que se hubiera publicado desde la
    terminación del examen, pero no se encontraron estudios de interés. La
    información acerca del carácter del examen colegiado del documento
    original y su disponibilidad figura en el apéndice 1. La información
    sobre el examen colegiado de este CICAD aparece en el apéndice 2. Este
    CICAD se aprobó como evaluación internacional en una reunión de la
    Junta de Evaluación Final celebrada en Washington, DC, Estados Unidos,
    los días 8-11 de diciembre de 1998. La lista de participantes en esta
    reunión figura en el apéndice 3. La Ficha internacional de seguridad
    química (ICSC 0276) preparada por el Programa Internacional de
    Seguridad de las Sustancias Químicas (IPCS, 1993), también se
    reproduce en el presente documento.

           El 2-furaldehído (C5H402) (CAS No 98-01-1) es un líquido de
    olor acre "semejante al de la almendra". Se encuentra en cantidades
    ínfimas en diversas fuentes de alimentos y se produce comercialmente
    en digestores de lotes o continuos en los cuales se hidrolizan
    pentosanos procedentes de residuos agrícolas a pentosas y éstas se
    ciclodeshidratan a 2-furaldehído. Entre los usos industriales cabe
    mencionar la producción de resinas, ruedas abrasivas, materiales
    refractarios, refinado de los aceites lubricantes y recuperación de
    disolventes. El 2-furaldehído se utiliza también, en cantidades muy
    pequeñas, como aromatizante.

           El 2-furaldehído está presente en numerosos alimentos, como
    producto natural o como contaminante. Se ha notificado su presencia en
    el agua potable y en la leche materna, pero las concentraciones no
    fueron suficientes para su cuantificación.

           Se dispone de mediciones de la exposición por inhalación en el
    puesto de trabajo y también se han efectuado estimaciones utilizando
    un sistema de computadora basado en los conocimientos, Estimación y
    evaluación de la exposición a la sustancia (EASE). En general, la
    exposición al compuesto en suspensión en el aire en todas las
    industrias es inferior a 8 mg/m3 (2 ppm), con un promedio ponderado
    por el tiempo (PPT) de ocho horas. No hay información suficiente para
    pronosticar exposiciones PPT de 15 minutos para la mayoría de las
    industrias; sin embargo, en la industria de los aromatizantes se ha

    estimado una exposición PPT de 15 minutos de 1,2 a 6,8 mg/m3 (0,3 y
    1,7 ppm). No se dispone de datos sobre mediciones de la exposición
    cutánea. Se han calculado las exposiciones cutáneas basadas en la EASE
    de 0,1 y 1 mg/cm2 al día para la mayoría de las industrias, con
    exposiciones superiores, entre 1 y 5 mg/cm2 al día, para las
    industrias de fabricación de materiales refractarios y ruedas

           Los datos toxicocinéticos son limitados, pero hay indicios de que
    el 2-furaldehído se absorbe fácilmente por las vías de exposición por
    inhalación y cutánea. Los estudios en animales demuestran que, tras la
    administración oral a ratas, el 2-furaldehído se absorbe fácilmente y
    excreta con rapidez sobre todo en la orina, aunque también se produce
    alguna eliminación a través del anhídrido carbónico exhalado. El
    metabolismo se caracteriza por la oxidación o la acetilación del grupo
    aldehído, seguida de la conjugación de la glicina. La 2-furoilglicina
    es el principal metabolito urinario; otros metabolitos secundarios son
    el ácido furoico, el ácido furanacrílico y el ácido furanacrilúrico.

           En el ser humano, se ha demostrado la absorción del vapor a
    través de los pulmones y la piel. El metabolismo en las personas
    parece ser semejante al de las ratas, excretándose la mayor parte de
    la dosis retenida como 2-furoilglicina urinaria. Se han detectado
    también como metabolitos secundarios el ácido furoico y el ácido
    furanacrilúrico. Se ha observado asimismo absorción cutánea a partir
    del 2-furaldehído líquido.

           Los datos sobre la toxicidad aguda en los animales son variables;
    en general, sin embargo, el 2-furaldehído es tóxico por inhalación y
    por vía oral (CL50 a los cuatro horas, 940 mg/m3 [235 ppm]; DL50 por
    vía oral, 120 mg/kg de peso corporal), no disponiéndose de información
    clara en relación con la vía cutánea. Se ha observado sistemáticamente
    irritación del sistema respiratorio y lesiones en los pulmones tras la
    exposición por inhalación a una dosis única y repetida. También se ha
    notificado irritación cutánea y ocular. Aparentemente no se detectó
    irritación en la garganta o en los ojos en personas expuestas a 40
    mg/m3 (10 ppm) durante ocho horas o a 80 mg/m3 (20 ppm) durante
    cuatro horas. En animales se han determinado concentraciones sin
    efectos adversos observados (NOAEL) de 80 mg/m3 (20 ppm) y 208 mg/m3
    (52 ppm) en estudios de hasta 13 semanas de duración en hámsteres y
    conejos, respectivamente, para los efectos no neoplásicos. Se han
    observado tumores malignos y benignos en ratas y ratones tras la
    exposición oral a 60 y 50 mg/kg de peso corporal, respectivamente,
    durante 103 semanas. El 2-furaldehído es claramente genotóxico  in
    vitro en células de mamíferos; aunque no se puede llegar a una
    conclusión definitiva sobre el potencial genotóxico del 2-furaldehído
     in vivo, no se puede descartar la posibilidad de que la
    genotoxicidad pueda contribuir al proceso carcinogénico. Estos
    factores impiden determinar de manera fidedigna una NOAEL para el

           La falta de datos disponibles que sirvan de base para la
    estimación de la exposición indirecta de las personas al 2-furaldehído
    del medio ambiente general impiden la caracterización de los posibles
    riesgos de cáncer para la población general.

           En el entorno del puesto trabajo, existe un riesgo potencial de
    efectos carcinogénicos y genotóxicos. El nivel de riesgo es incierto;
    en consecuencia, existe el requisito permanente de reducir los niveles
    de exposición todo lo que sea posible razonablemente con la tecnología
    disponible en la actualidad.

           No hay datos adecuados sobre los efectos en la reproducción o en
    el desarrollo; por consiguiente, no es posible evaluar el riesgo para
    la salud humana con respecto a estos efectos finales.

           Las emisiones más altas notificadas de 2-furaldehído al medio
    ambiente son las de la industria de la pasta de madera. El
    2-furaldehído se libera a la atmósfera en la combustión natural y
    antropogénica de madera.

           No se prevén efectos atmosféricos, puesto que el 2-furaldehído se
    destruye al reaccionar con los radicales hidroxilo, con una semivida
    atmosférica calculada de 0,44 días. En el aire urbano, la reacción con
    radicales nitrato puede representar un proceso de degradación
    adicional. También se puede producir fotooxidación directa. Los bajos
    valores de la presión de vapor y de la constante de Henry parecen
    indicar que solamente se produce una volatilización lenta del
    2-furaldehído de la superficie del agua y del suelo.

           No se prevé que con el pH del medio ambiente se produzca
    hidrólisis en el agua. El bajo coeficiente de reparto octanol/agua
    (log  Kow 0,41) deja entrever una escasa capacidad de
    bioacumulación. Los coeficientes de sorción ( Koc) parecen indicar
    una sorción escasa a partículas y una movilidad alta en el suelo.

           El 2-furaldehído se biodegrada fácilmente en sistemas aerobios
    utilizando fangos cloacales y en el agua superficial. También se
    produce degradación en condiciones anaerobias, gracias a una serie de
    bacterias y otros microorganismos capaces de utilizar el compuesto
    como única fuente de carbono. A concentraciones altas (>1000
    mg/litro), el 2-furaldehído inhibe el crecimiento y la actividad
    metabólica de cultivos anaerobios no adaptados. Sin embargo, la
    aclimatación aumenta la capacidad de degradación del compuesto en los
    fangos anaerobios.

           Las concentraciones más altas notificadas de 2-furaldehído en
    aguas residuales industriales corresponden al líquido condensado de
    los evaporadores de sulfito (alrededor del 15% de la corriente de
    residuos de las fábricas de pasta de madera), con un promedio de

    274 mg/litro. En un estudio aislado se cuantificó la concentración de
    2-furaldehído en el aire de espacios cerrados y abiertos en alrededor
    de 1 µg/m3; en otros estudios se ha detectado el compuesto, pero no
    se ha cuantificado.

           Se han notificado umbrales tóxicos para diversos microorganismos
    en una gama de 0,6 a 31 mg/litro. Las CL50 aguda para los peces
    oscila entre 16 y 32 mg/litro.

           Teniendo cuenta las concentraciones pronosticadas estimadas en el
    medio ambiente a partir de los residuos de la pasta de madera (se
    considera que es el peor de los casos) y la aplicación de un factor de
    incertidumbre de 1000 a los datos limitados de las pruebas de
    toxicidad aguda, cabe prever que las emisiones de 2-furaldehído
    plantearán un riesgo bajo para los organismos acuáticos. No se dispone
    de datos sobre los cuales basar una evaluación del riesgo terrestre,
    pero se supone que las emisiones a la tierra son bajas.

    See Also:
       Toxicological Abbreviations