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 Ms G.K. Montizaan,
    National Institute of Public Health and
    Environmental Hygiene, Bilthoven, Netherlands

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

    World Health Orgnization
    Geneva, 1994

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    coordination of laboratory testing and epidemiological studies, and
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    WHO Library Cataloguing in Publication Data


        (Environmental health criteria ; 161)

        1.Phenols - standards  2.Environmental exposure 

        ISBN 92 4 157161 6        (NLM Classification: QD 341.P5)
        ISSN 0250-863X

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    1. SUMMARY

         1.1. Identity, physical and chemical properties, analytical
         1.2. Sources of human and environmental exposure
         1.3. Environmental transport, distribution and transformation
         1.4. Environmental levels and human exposure
         1.5. Kinetics and metabolism
         1.6. Effects on laboratory mammals, and  in vitro test
         1.7. Effects on humans
         1.8. Effects on organisms in the environment
         1.9. Summary of evaluation
               1.9.1. Human health
               1.9.2. Environment


         2.1. Identity
         2.2. Physical and chemical properties
         2.3. Conversion factors
         2.4. Analytical methods
               2.4.1. Sampling and pre-treatment
               2.4.2. Analysis


         3.1. Natural sources
         3.2. Anthropogenic sources
               3.2.1. Production
               3.2.2. Industrial processes
               3.2.3. Non-industrial sources
         3.3. Endogenous sources
         3.4. Uses


         4.1. Transport and distribution between media
         4.2. Abiotic degradation
               4.2.1. Air
               4.2.2. Water
         4.3. Biodegradation


         5.1. Environmental levels
               5.1.1. Air
               5.1.2. Water and sediment
         5.2. Occupational exposure
               5.2.1. Production
               5.2.2. Application of phenolic resins
               5.2.3. Other occupational situations
         5.3. General population exposure
               5.3.1. Indoor air
               5.3.2. Food and drinking-water


         6.1. Absorption
               6.1.1. Animal uptake studies
               6.1.2. Human uptake studies
         6.2. Distribution
         6.3. Metabolic transformation
               6.3.1. Metabolite identification
               6.3.2. Covalent binding to macromolecules
               6.3.3. Location
         6.4. Elimination and excretion
         6.5. Biological monitoring


         7.1. Single exposure
               7.1.1. LD50 values
               7.1.2. Effects
         7.2. Short-term exposure
               7.2.1. Oral exposure
               7.2.2. Dermal exposure
               7.2.3. Inhalation exposure
               7.2.4. Subcutaneous exposure
               7.2.5. Ear exposure
         7.3. Skin and eye irritation; sensitization
         7.4. Long-term exposure
         7.5. Reproduction, embryotoxicity and teratogenicity
               7.5.1. Reproductive toxicity
               7.5.2. Embryotoxicity/teratogenicity
               In vivo studies
               In vitro studies

         7.6. Mutagenicity and related end-points
               7.6.1. Mutagenicity studies
               Bacterial systems
               Non-mammalian eukaryotic systems
               Mammalian  in vitro systems
               Mammalian  in vivo systems: somatic
               Mammalian  in vivo systems: germ cells
         7.7. Carcinogenicity
               7.7.1. Oral exposure
               7.7.2. Dermal exposure
               7.7.3. Inhalation exposure
               7.7.4. Two-stage carcinogenicity studies
         7.8. Special studies
               7.8.1. Neurotoxicity
               7.8.2. Myelotoxicity
               7.8.3. Immunotoxicology
               7.8.4. Biochemical effects


         8.1. General population exposure
               8.1.1. Controlled studies
               8.1.2. Case reports
               Dermal exposure
               Oral exposure
               Inhalation exposure
               Exposure by injection
         8.2. Occupational exposure
         8.3. Organoleptic data


         9.1. Microorganisms
         9.2. Aquatic organisms
               9.2.1. Freshwater organisms
               Short-term studies
               Long-term studies
               9.2.2. Marine organisms
               Short-term studies
               Long-term studies
               9.2.3. Accumulation
               9.2.4. Metabolism
         9.3. Terrestrial organisms


         10.1. Evaluation of human health risks
               10.1.1. Exposure
               10.1.2. Toxicity
               10.1.3. Evaluation

         10.2. Evaluation of effects on the environment
               10.2.1. Environmental levels
               10.2.2. Toxicity
               10.2.3. Evaluation









    Dr L.E. Hansen, dk-Teknik, Soeborg, Denmark

    Dr R.J. Kavlock, Developmental Toxicology Division, Health Effects
         Research Laboratory, US Environmental Protection Agency,
         Research Triangle Park, North Carolina, USA

    Dr C.J. Price, Neurotoxicology Program Development, Center for Life
         Sciences and Toxicology, Research Triangle Institute, Research
         Triangle Park, North Carolina, USA

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

    Dr A. Smith, Health and Safety Executive, Toxicology Unit, Bootle,
         Merseyside, United Kingdom ( Joint Rapporteur)

    Professor J.A. Sokal, Institute of Occupational Medicine and
         Environmental Health, Sosnowiec, Poland ( Chairman)

    Dr S.H.H. Swierenga, Health and Welfare Canada, Drugs Directorate,
         Ottawa, Ontario, Canada ( Joint Rapporteur)

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


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


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

                                  *   *   *

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

                                  *   *   *

         This publication was made possible by grant number 5 U01
    ES02617-14 from the National Institute of Environmental Health
    Sciences, National Institutes of Health, USA.


         A Task Group on Environmental Health Criteria for Phenol met at
    the British Industrial and Biological Research Association (BIBRA)
    Toxicology International, Carshalton, United Kingdom from 26 to 30
    April 1993. Dr D. Anderson welcomed the participants on behalf of
    the host institution, and Professor F. Valic opened the Meeting on
    behalf of the three cooperating organizations of the IPCS
    (UNEP/ILO/WHO). The Task Group reviewed and revised the draft
    monograph and made an evaluation of the risks for human health and
    the environment from exposure to phenol.

         The first draft of this monograph was prepared by Ms G.K.
    Montizaan, National Institute of Public Health and Environmental
    Hygiene, Bilthoven, the Netherlands.

         Professor F. Valic was responsible for the overall scientific
    content of the monograph and for the organization of the meeting,
    and Dr P.G. Jenkins, IPCS, was responsible for the technical editing
    of the monograph.

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


    DMBA       dimethylbenzathraline

    EEC        European Economic Community

    LOAEL      lowest-observed-adverse-effect level

    MATC       maximum acceptable tolerance concentration

    NOAEL      no-observed-adverse-effect level

    NOEL       no-observed-effect level

    NOLC       no-observed lethal concentration

    PCE        polychromatic erythrocytes

    TT         toxicity threshold

    1.  SUMMARY

    1.1  Identity, physical and chemical properties, analytical methods

         Phenol is a white crystalline solid which melts at 43 °C and
    liquefies upon contact with water. It has a characteristic acrid
    odour and a sharp burning taste. It is soluble in most organic
    solvents; its solubility in water is limited at room temperature;
    above 68 °C it is entirely water-soluble. Phenol is moderately
    volatile at room temperature. It is a weak acid, and in its ionized
    form very sensitive to electrophile substitution reactions and

         Phenol may be collected from environmental samples by
    absorption in NaOH solution or onto solid sorbents. Desorption is
    achieved by acidification, steam distillation and ether extraction
    (from solutions) or by thermal or liquid desorption (from solid
    sorbents). The most important analytical techniques are gas
    chromatography in combination with flame ionization/electron capture
    detection, and high-performance liquid chromatography in combination
    with ultraviolet detection. The lowest reported detection limit for
    air is 0.1 µg/m3. Phenol can be measured in blood and urine; in
    urine samples a detection limit of 0.5 µg/litre has been reported.

    1.2  Sources of human and environmental exposure

         Phenol is a constituent of coal tar, and is formed during the
    natural decomposition of organic materials. The major part of phenol
    present in the environment, however, is of anthropogenic origin.
    Production and use of phenol and its products, especially phenolic
    resins and caprolactam, exhaust gases, residential wood burning and
    cigarette smoke are potential sources. Another potential source is
    the atmospheric degradation of benzene under the influence of light,
    whereas the presence of phenol in liquid manure may also contribute
    considerably to its atmospheric levels. Benzene and phenol
    derivatives may, by  in vivo conversion, form a source of
    endogenous human phenol exposure.

         The worldwide production of phenol appeared to be fairly
    constant throughout the 1980s, the USA being the most important
    producer. Its major use is as a feedstock for phenolic resins,
    bisphenol A and caprolactam. Some medical and pharmaceutical
    applications are also known.

    1.3  Environmental transport, distribution and transformation

         The main emissions of phenol occur to air. The major part of
    phenol in the atmosphere will be degraded by photochemical reactions
    to dihydroxybenzenes, nitrophenols and ring cleavage products, with
    an estimated half-life of 4-5 h. A minor part will disappear from

    the air by wet deposition (rain). Phenol is expected to be highly
    mobile in soil, but transport and reactivity may be affected by pH.

         Phenol in water and soil may be degraded by abiotic reactions
    as well as microbial activity to a number of compounds, the most
    important being carbon dioxide and methane. The proportion of
    biodegradation to the overall degradation of phenol is determined by
    many factors, such as concentration, acclimation, temperature, and
    the presence of other compounds.

    1.4  Environmental levels and human exposure

         No data are available on atmospheric phenol levels. Background
    levels are expected to be less than 1 ng/m3. Urban/suburban levels
    vary from 0.1 to 8 µg/m3, while concentrations in source-dominated
    areas (industry) were reported to be up to two orders of magnitude
    higher. Phenol has been detected in rain, surface water and ground
    water, but data are very scarce. Elevated phenol levels have been
    reported in sediments and ground waters due to industrial pollution.

         Occupational exposure to phenol may occur during the production
    of phenol and its products, during the application of phenolic
    resins (wood and iron/steel industry) and during a number of other
    industrial activities. The highest concentration (up to 88 mg/m3)
    was reported for workers in the ex-USSR quenching coke with
    phenol-containing waste water. Most other reported concentrations
    did not exceed 19 mg/m3.

         For the general population, cigarette smoke and smoked food
    products are the most important sources of phenol exposure, apart
    from the exposure via air. Exposure by way of drinking-water and
    inadvertently contaminated food products should be low; phenol has
    an objectionable smell and taste, which in most cases leads to
    non-acceptance by the consumer.

    1.5  Kinetics and metabolism

         Phenol is readily absorbed by all routes of exposure. After
    absorption, the substance is rapidly distributed to all tissues.

         Absorbed phenol mainly conjugates with glucuronic acid and
    sulfuric acid and, to a lesser extent, hydroxylates into catechol
    and hydroquinone. Phosphate conjugation also occurs. The formation
    of reactive metabolites (4,4-biphenol and diphenoquinone) has been
    demonstrated in  in vitro studies with activated human neutrophils
    and leucocytes.

         The relative amounts of glucuronide and sulfate conjugates vary
    with dose and animal species. A shift from sulfation to
    glucuronidation was observed in rats after increasing the phenol

         The liver, the lung, and the gastrointestinal mucosa are the
    most important sites of phenol metabolism. The relative role played
    by these tissues depends on route of administration and dose.

          In vivo and  in vitro studies have demonstrated covalent
    binding of phenol to tissue and plasma proteins. Some phenol
    metabolites also bind to proteins.

         Urinary excretion is the major route of phenol elimination in
    animals and humans. The rate of urinary excretion varies with dose,
    route of administration, and species. A minor part is excreted in
    the faeces and expired air.

    1.6  Effects on laboratory mammals, and in vitro test systems

         Phenol has moderate acute toxicity for mammals. Oral LD50
    values in rodents range from 300 to 600 mg phenol/kg body weight.
    Dermal LD50 values for rats and rabbits range from 670 to 1400
    mg/kg body weight, respectively, and the 8-h LC50 for rats by
    inhalation is more than 900 mg phenol/m3. Clinical symptoms after
    acute exposure are neuromuscular hyperexcitability and severe
    convulsions, necrosis of skin and mucous membranes of the throat,
    and effects on lungs, nerve fibres, kidneys, liver, and the pupil
    response to light.

         Solutions of phenol are corrosive to skin and eyes. Phenol
    vapours can irritate the respiratory tract. There is evidence that
    phenol is not a skin sensitizer.

         The most important effects reported in short-term animal
    studies were neurotoxicity, liver and kidney damage, respiratory
    effects and growth retardation. Toxic effects in rat kidney have
    been reported to occur at oral dose levels of 40 mg/kg per day or
    more. Liver toxicity was evident in rats administered at least 100
    mg/kg per day. In a limited 14-day study in rats, an oral
    no-observed-adverse-effect level (NOAEL) of 12 mg/kg per day was
    reported, based on kidney effects. In this experiment miosis (an
    iris response to light) was still inhibited at 4 mg/kg per day;
    however, the health significance of this finding is not clear. Some
    biological changes were reported to occur in the intestinal mucosa
    and kidneys of mice at dose levels below 1 mg/kg per day, a finding
    of uncertain toxicological significance.

         There are no adequate studies on the reproductive toxicity of
    phenol. Phenol has been identified as a developmental toxicant in
    studies with rats and mice. In two multiple dose rat studies, NOAEL
    values of 40 mg/kg per day (the lowest-observed-adverse-effect level
    (LOAEL) was 53 mg/kg per day) and 60 mg/kg per day (the LOAEL was
    120 mg/kg per day) have been reported. In the mouse, the NOAEL was
    140 mg/kg per day (the LOAEL was 280 mg/kg per day).

         The majority of bacterial mutagenicity tests have given
    negative results. Mutations, chromosomal damage and DNA effects have
    been observed in mammalian cells in vitro. Phenol has no effect on
    intercellular communication (measured as metabolic cooperation) in
    cultured mammalian cells. Induction of micro-nuclei in bone marrow
    cells of mice has been observed in some studies. No micronuclei were
    observed in mice studies at lower doses.

         Two carcinogenicity studies have been conducted with male and
    female rats and mice receiving phenol in their drinking-water.
    Malignancies (e.g., C-cell thyroid carcinoma, leukaemia) were only
    seen in low-dose male rats. No adequate dermal or inhalation
    carcinogenicity studies have been conducted. Two-stage
    carcinogenicity studies have shown that phenol, applied repeatedly
    to mouse skin, has promoting activity.

    1.7  Effects on humans

         A wide range of adverse effects has been reported following
    well-documented human exposure to phenol by the dermal, oral or
    intravenous routes. Gastrointestinal irritation has been reported
    following ingestion. Local effects following dermal exposure range
    from painless blanching or erythema to corrosion and deep necrosis.
    Systemic effects include cardiac dysrhythmias, metabolic acidosis,
    hyperventilation, respiratory distress, acute renal failure, renal
    damage, dark urine, methaemoglobinaemia, neurological effects
    (including convulsions), cardiovascular shock, coma and death. The
    lowest reported dose resulting in a human death was 4.8 g by
    ingestion; death occurred within 10 min.

         The potential for poisoning through inhalation of phenol
    vapours has long been recognized, but no cases of death following
    this route of exposure have been reported. Symptoms associated with
    inhalation of phenol included anorexia, weight loss, headache,
    vertigo, salivation and dark urine.

         Phenol is not a sensitizing agent.

         The human odour threshold for phenol has been reported to range
    from 0.021 to 20 mg/m3 in air. The odour threshold for phenol in
    water has been reported to be 7.9 mg/litre, and the taste threshold
    0.3 mg/litre in water.

         Adequate human data on the carcinogenicity of phenol are not

    1.8  Effects on organisms in the environment

         In studies on single bacteria species, the EC50 values found
    for growth inhibition varied from 244 to 1600 mg phenol/litre. A
    toxicity threshold of 64 mg phenol/litre was found. Values for

    protozoa and fungi were of the same order of magnitude as for
    bacteria; for algae, they were somewhat lower.

         Phenol is toxic to higher freshwater organisms. The lowest
    LC50 or EC50 values for crustaceans and fish lie between 3 and 7
    mg phenol/litre. The data on the acute toxicity to marine organisms
    are comparable with those for freshwater organisms. In long-term
    studies on crustacea and fish species, a remarkable difference in
    sensitivity has been observed; the LC1 values from embryo-larval
    tests on  Salmo and  Carassius proved to be much lower (0.2 and 2
    µg phenol/litre, respectively) than the corresponding values for
    other fish species (NOLC 2.2-6.1 mg/litre) and amphibia, or from
    reproduction tests on crustacea (NOLC 10 mg phenol/litre). Data from
    long-term tests on marine organisms are not available.

         The bioconcentration factors of phenol in various types of
    aquatic organisms are in general very low (< 1-10), although some
    higher values (up to 2200) have also been reported. Phenol,
    therefore, is not expected to bioaccumulate significantly.

         The available data concerning the fate and effects of phenol in
    terrestrial organisms are very scarce. A 120-h EC50 for millet was
    found to be 120-170 mg/litre, and in a contact test the LC50 for
    earthworm species was 2.4-10.6 µg/cm2.

    1.9  Summary of evaluation

    1.9.1  Human health

         The general population is primarily exposed to phenol by
    inhalation. Repeated oral exposure may arise from consumption of
    smoked food or drinking-water.

         Data are inadequate to determine the degree of exposure of the
    general population, but an upper-limit estimate of the daily intake
    can be made. On the basis of "the worst case scenario", an estimate
    can be made assuming that an individual will be maximally exposed to
    phenol through continuous inhalation of heavily contaminated air
    with frequent consumption of smoked food items and of drinking-water
    containing phenol up to the taste threshold. The estimated maximal
    total daily intake of phenol for such a 70-kg individual is
    calculated to be 0.1 mg/kg body weight per day.

         The lowest NOAEL values identified in animal experiments are
    for kidney and developmental effects, and in rats lie within the
    range of 12-40 mg/kg body weight per day. Using an uncertainty
    factor of 200, a range of 60-200 µg/kg body weight per day is
    recommended as the upper limit of the total daily intake (TDI).
    Considering the upper-limit estimate of human daily intake of 100
    µg/kg body weight per day, it is concluded that the average general
    population exposure to phenol from all sources is below this range.

         A reason for concern is some evidence that phenol may be
    genotoxic and the fact that there is insufficient data to discount
    with certainty the possible carcinogenicity of the compound. The
    evaluation must be kept under periodic review.

    1.9.2  Environment

         Phenol is not expected to bioaccumulate significantly. Phenol
    is toxic to aquatic organisms; an environmental concern level of
    0.02 µg/litre can be determined applying the modified US EPA method.
    Adequate data on plants and terrestrial organisms are lacking.

         Intercompartmental transport of phenol mainly occurs by wet
    deposition and by leaching through soil. Generally, the compound is
    not likely to persist in the environment. The scarce exposure data
    do not allow the evaluation of the risk from phenol to either
    aquatic or terrestrial ecosystems. However, in view of the derived
    environmental concern level for water, it is reasonable to assume
    that aquatic organisms may be at risk in any surface or sea water
    contaminated with phenol.


    2.1  Identity

    Chemical formula:  C6H6O

    Chemical structure:


    Relative molecular mass:    94.11

    Common name:                phenol

    Common synonyms:            acidum carbolicum, acidum phenolicum,
                                acidum phenylicum, benzaphenol, benzene
                                phenol, benzenol carbolic acid,
                                hydroxybenzene (IUPAC), oxybenzene,
                                monohydroxybenzene, monophenol, phenic
                                acid, phenol alcohol, phenyl hydrate,
                                phenyl hydroxide, phenylic acid

    Common trade names:         carbololie (NLD), fenololie (NLD),
                                kristalliertes Kreosot (GER),
                                Steinkohlenkreosot (GER),
                                Steinkohlenteerkreosot (GER), venzénol
                                (FRA), ENT 1814.

    CAS registry number:        108-95-2

    CAS chemical name:          phenol

    2.2  Physical and chemical properties

         Some physical and chemical properties of phenol are given in
    Table 1.

    Table 1.  Some physical and chemical properties of phenola

    Boiling point (101.3 Pa)                181.75 °C

    Melting point                           43 °C
                                            40.9 °C (ultrapure material)

    Relative density (20 °/4 °)b            1.071

    Relative vapour density (air = 1)       3.24

    Vapour pressure     (20 °C)             0.357 mmHg
                        (50 °C)             2.48 mmHg
                        (100 °C)            41.3 mmHg

    Saturation concentration in air (20°C)  0.77 g/m3

    Solubility in water (16 °C)             67 g/litrec

    Log n-octanol/water partition
    coefficient (log Pow)                   1.46d

    Dissociation constant in water
    at 20 °C (Ka)                           1.28 x 10-10

    Flash-point         (closed cup)        80 °C
                        (open cup)          79 °C
                                            85 °Ce

    Flammability limits                     1.3-9.5%

    a From: Kirk-Othmer (1980); RIVM (1986)
    b Weast (1987)
    c Above 68.4 °C phenol is entirely soluble in water
    d The Pow of phenol is very much dependent on pH; pH at log
      Pow = 1.46 was not given
    e Budavari  et al. (1989)

         Phenol has a melting point of 43 °C and forms white to
    colourless crystals (Budavari  et al., 1989). It has also been
    described as a colourless to pink solid or thick liquid (NIOSH,
    1985a). Phenol has a characteristic acrid smell and a sharp burning
    taste. Odour and taste threshold values are reported in section 8.3.
    In the molten state, it is a clear, colourless liquid with a low
    viscosity. A solution with approximately 10% water is called
    phenolum liquefactum, as this mixture is liquid at room temperature.
    Phenol is soluble in most organic solvents (aromatic hydrocarbons,
    alcohols, ketones, ethers, acids, halogenated hydrocarbons). The
    solubility is limited in aliphatic solvents.

         The chemical properties of phenol are affected by the resonance
    stabilization possibilities of phenol and, in particular, of the
    phenolate ion. Because of this, phenol reacts as a mild acid. In the
    presence of electrophilic groups (meta-indicators), the acidic
    properties are emphasized.

         Phenol is sensitive to oxidizing agents. Splitting of the
    hydrogen atom from the phenolic hydroxyl group is followed by
    resonance stabilization of the resulting phenyloxy radical. The
    radical formed can easily be further oxidized. Depending on the
    oxidizing agent applied and the reaction conditions, various
    products, such as dihydroxy- and trihydroxybenzenes and quinones are
    formed. These properties make phenol suitable as an antioxidant,
    functioning as a radical trapping agent. Phenol undergoes numerous
    electrophilic substitution reactions, such as halogenation and
    sulfonation. It also reacts with carbonyl compounds in both acidic
    and alkaline media. In the presence of formaldehyde, phenol is
    readily hydroxymethylated with subsequent condensation to resins.

    2.3  Conversion factors

         1 mg/m3 = 0.26 ppm
         1 ppm = 3.84 mg/m3

    2.4  Analytical methods

         Analytical methods for phenol are shown in Table 2.

    2.4.1  Sampling and pre-treatment

         Phenol in air samples may be collected by absorption in NaOH
    solution contained in wash bottles or on filters impregnated with
    NaOH solution. Phenol in air, water and solid waste samples may be
    collected (directly or after extraction) in tubes containing solid
    sorbent (Tenax, silica gel or, less commonly, carbon) (IARC, 1989).
    For large air volumes, the NaOH method is usually preferred, whereas
    for smaller quantities (personal air sampling, for instance) solid
    sorbent tubes have been reported to be more practical (RIVM, 1986).

         Release of phenol from aqueous solutions (including NaOH
    sorbent, and also urine) is achieved by acidification, steam
    distillation and/or ether extraction. After adsorption onto Tenax,
    thermal desorption at 250 °C is usually preferred (the whole sample
    may be inserted directly into a gas chromatograph), whereas, in the
    case of silica gel, liquid desorption with chloroform is generally
    applied. There is a small possibility of chemical conversion during
    heating, whereas Tenax may react with ozone to form small quantities
    of phenol. Only one analysis per sample is possible in the case of
    thermal desorption. The use of liquid desorption allows more
    analyses per sample, but because of the unavoidable dilution the
    detection limit is higher (RIVM, 1986).

    Table 2.  Methods for the detection of phenol in air
    Sampling                              Volume of air   Pre-treatment           Analysis                 Detection limit  Reference
                                          (litre)         before analysis         (µg/m3)

    Absorbance in NaOH solution           100             acidification           GC and FID               10 µg per        NIOSH (1984)
    in a wash bottle; 1 litre/min         sample

    Absorbance in NaOH solution           25 000          acidification and       GC and FID               4                Katz (1977)
    in an impinger; 20 litre/min                          steam distillation

    Glass fibre filter impregnated with   600             acidification and       GC and FID               13               Kifune (1979)
    NaOH and glycerol; 120 litre/min                      extraction with ether

    Absorbance in NaOH solution in        1000            acidification and       colorimetry with         2                Katz (1977)
    an impinger; 28 litre/min                             steam distillation      4-amino antipyrine

    Absorbance in NaOH solution           -               none                    colorimetry with         700              Hensehler (1975)
    in a wash bottle; 1 litre/min                                                 4-amino antipyrine

    Absorbance in NaOH solution in        150             conversion in an        HPLC with UV detector    0.2              Kuwata et al.
    a sinter wash bottle; 1-2 litre/min                   azophenol derivate      (254 nm)                                  (1980)

    Absorbance in Na2CO3 solution;        30              calibration at pH = 10  UV at 235 nm at 2 pH     160              Zavorovskaya &
    1 litre/min                                           and pH = 7              values                                    Nekhorosheva (1981)

    Absorbance in NaOH solution in        300             calibration at pH = 12  UV at 241 and 295 nm     20               Bergshoeff (1960)
    an impinger; 28 litre/min                             and at pH = 6

    Tenax with and without KOH;           5               thermal desorption;     GC and FID               0.1              Hoshika & Muto
    0.25 litre/min                                        250 °C                                                            (1979)

    Tenax; 0.1 litre/min                  4               thermal desorption;     GC and FID               1                Russell (1975)
                                                          260 °C

    Tenax; 0.5-1 litre/min                70              thermal desorption;     GC and MS                0.3              Hagemann et
                                                          250 °C                                                            al. (1978)

    Table 2 (contd)
    Sampling                              Volume of air   Pre-treatment           Analysis                 Detection limit  Reference
                                          (litre)         before analysis         (µg/m3)

    Tenax; 0.75 litre/min                 90              thermal desorption;     IR with 20 m gas         300              Podolak et al.
                                                          300 °C                  cuvette                                   (1981)

    Silica gel                            25              liquid desorption       GC and FID               3                Dimitriev &
                                                          with chloroform                                                   Mishchikhin (1983)

    Silica gel; 0.05-2 litre/min          10              liquid desorption       HPLC with UV detector    50               Oomems &
                                                          with chloroform         (275 nm)                                  Schuurhuis (1983)

    Drägen tube gas detection             0.5             none                    reading of colorisation  19 000           Leichnitz (1982)

    2.4.2  Analysis

         The most important analytical techniques for the detection of
    phenol are gas chromatography (GC) in combination with flame
    ionization detection (FID), and high-performance liquid
    chromatography (HPLC) in combination with ultraviolet (UV)
    detection. The identification of phenol by GC/FID has been improved
    by reaction of phenols with bromide or pentafluoro-benzyl bromide,
    and the use of electron capture detection (Hoshika & Muto, 1979; US
    EPA, 1986a). The identification of phenol using HPLC can be improved
    by reaction with, for example,  p-nitrobenzene diazonium
    tetrafluoroborate to form azo derivatives (Kuwata  et al., 1980).

         Detection limits of the above techniques for air samples are
    given in Table 2. For the GC/FID detection of phenol in water, using
    electron capture detection following derivatization with
    pentafluorobenzyl bromide, a detection limit of approximately 0.2
    µg/litre has been reported (US EPA, 1986a).

         GC in combination with mass spectrometry (MS) is more sensitive
    than with FID, but is more expensive. This technique, using either
    packed or capillary columns, was reported to have practical
    quantitative limits of approximately 1 mg phenol/kg wet weight for
    soil/sediment samples, 1-200 mg phenol/kg for wastes, and 10
    µg/litre for groundwater samples (US EPA, 1986b,c).

         Another reported analytical technique is colorimetry after
    reaction of phenol with 4-amino antipyrine, in the presence of
    potassium ferricyanide, to form an antipyrine dye. The detection
    limit of this technique for water samples, after steam distillation,
    was reported to be 1 µg/litre (American Public Health Association,
    1985). For air samples of 1 m3, the detection limit was reported
    to be 2 µg/m3 (see Table 2). The interference by para-substituted
    phenols and chlorophenols is low (RIVM, 1986).

         Infrared (IR) detection of phenol is a rather insensitive
    method, and is highly susceptible to interference by other compounds
    such as water vapour. However, it is a rapid and specific method
    which allows directly readable continuous measurement. It is
    considered to be attractive only at air concentrations of more than
    1000 µg/m3, for example in leakage tests and industrial warning
    systems (RIVM, 1986). Also directly readable is the Dräger gas
    detection tube (see Table 2); however, the detection limit is very
    high (> 19 000 µg/m3).

         For the GC/FID detection of total phenol in urine samples,
    after acidification and ether extraction, a detection limit of 0.5
    µg/litre was estimated (NIOSH, 1985b). Colorimetric methods for the
    determination of free phenol in both urine and blood are available.
    In one method, phenol reacts with  p-nitroaniline following
    deproteinization and extraction with diethyl ether. Other phenols

    will interfere (Müting  et al., 1970). In another method, phenol
    reacts with ammonia and  N-chlorosuccinimide in alkaline media with
    sodium nitroprusside as a catalyst. This method was found to be
    applicable in the range of 3-24 mg/litre, using spiked samples of
    urine (Amlathe  et al., 1987). The concentration of total phenol in
    urine and plasma can be determined by GC/MS following hydrolysis of
    glucuronide and sulfate conjugates with sulfuric acid and
    derivatization with propanoic anhydride. The detection limit is
    reported to be 10 µg/litre (Pierce & Nerland, 1988).


    3.1  Natural sources

         Phenol is a constituent of coal tar, and is formed during the
    natural decomposition of organic materials. Increased environmental
    levels may result from forest fires (Hubble  et al., 1981).

         Phenol has been detected among the volatile components from
    liquid manure at concentrations of 7-55 µg/kg dry weight (Spoelstra,
    1978). In the Netherlands, for example, the contribution from this
    source to the overall phenol emission into air in 1983 has been
    calculated to be 15%, assuming complete volatilization of phenol and
    an average phenol concentration in manure of 30 µg/kg dry weight
    (RIVM, 1986).

    3.2  Anthropogenic sources

    3.2.1  Production

         The most commonly used production method for phenol, on a
    worldwide scale, is from cumene (isopropylbenzene). In the USA, for
    example, more than 98% of phenol is produced by this method (IARC,
    1989). Phenol is also produced from chlorobenzene and toluene. A
    small but steady supply of phenol is recovered as a by-product of
    metallurgical coke manufacture (IARC, 1989). The emission factor of
    phenol into air during production by the cumene process has been
    reported to be 0.16 g phenol emitted per kg phenol produced (UBA,

         In Table 3, information is presented concerning the production
    of phenol in various countries in 1981. This information was derived
    from the open literature (Chemfacts, 1978-1981; United Nations,
    1980; SRI, 1982; CID-TNO, 1984; IARC, 1989) and, where necessary,
    was extrapolated to 1981. There have been no major production
    changes according to data available up to 1986 (IARC, 1989).

    3.2.2  Industrial processes

         Phenol is the basic feedstock from which a number of
    commercially important materials are made, including phenolic
    resins, bisphenol A (2,2-bis-1-hydroxyphenylpropane), capro-lactam,
    alkyl phenols, as well as chlorophenols such as pentachlorophenol
    (IARC, 1989).

    Table 3.  Production of phenol in 1981 and 1986 (kilotonne/year)
    Country                       Production          Production
                                  in 1981a            in 1986b

    Brazil                        50

    Bulgaria                      35

    Czechoslovakia                44                  46

    Finland                       32

    France                        150

    Germany, Federal
    Republic of                   247

    Italy                         223

    India                         14

    Japan                         215                 260

    Mexico                        20

    The Netherlands               166

    Poland                        66

    Romania                       66

    Spain                         55                  70

    United Kingdomc               110                 53

    USA                           1350                1413

    USSR                          497                 515

    Other countries               34

    European Community (total)    920

    Total                         3374

    a  Chemfacts (1978-1981); United Nations (1980); SRI (1982); CID-TNO
       (1984); IARC (1989)
    b  From IARC (1989)
    c  Phenol is no longer produced in the UK

         The most important phenol emissions result from the use of
    phenolic resins. Phenolic resins are used as a binding material in,
    for example, insulation materials, chipboard and triplex, paints and
    casting sand foundries. Their contents vary from 2-3% for insulation
    material to > 50% for moulds (Bollig & Decker, 1980). Emissions are
    approximately proportional to the concentration of free phenol,
    which is present as a monomer in these materials (1-5%) (Bollig &
    Decker, 1980). In addition, phenol may be released as a result of
    thermal decomposition of the resins.

         In foundries, phenol emissions develop both during the
    production of moulds and kernels and during founding (TNO, 1978).
    The content of free phenol may rise by up to 12% (Ryser & Ulmer,
    1980). Emission factors reported by RIVM (1986) were 0.35 g phenol
    emitted per kg used casting sand, 2-5 g phenol emitted per kg resin
    in the production of casting sand, and 10 g phenol emitted per kg
    resin during the production of moulds by the "hot-box" procedure.

         Other industrial activities in which phenol may be emitted to
    the air, as well as some of their reported emission factors, are
    listed below:

    *    production of phenol resins (0-0.5 g phenol emitted per kg
         resin produced) (RIVM, 1986)
    *    production of phenols and phenol derivatives
    *    production of caprolactam (0.02-0.05 g phenol emitted per kg
         cyclohexanone (an intermediate) produced (RIVM, 1986)
    *    production of cokes
    *    production of insulation materials
    *    process emissions

         Emissions to water may also result from processing.

    3.2.3  Non-industrial sources

         Phenol has been detected in the exhaust gases of private cars
    at concentrations of 0.3 ppm (approximately 1.2 mg/m3) to 1.4-2.0
    ppm (5.4-7.7 mg/m3) (Kuwata  et al., 1980; Verschueren, 1983). It
    has also been identified in cigarette smoke, in quantities that are
    comparable to an average emission of 0.4 mg/cigarette (Groenen,
    1978). Emission gases from all material incinerators and home fires,
    especially wood-burning, may contain substantial quantities of
    phenol (Den Boeft  et al., 1984).

         Another potential source of phenol is the atmospheric
    degradation of benzene under the influence of light (Hoshino &
    Akimoto, 1978).

         Phenols have been detected in smoked foods (section 5.3.2).

    3.3  Endogenous sources

         An important additional source of human phenol exposure may be
    the  in vivo formation from various xenobiotics, e.g., benzene
    (Pekari  et al., 1992).

    3.4  Uses

         The largest single use of phenol is the production of phenolic
    resins. Next is its use in the production of caprolactam, an
    intermediate in the production of nylon 6, and 2,2-bis-1-
    hydroxyphenylpropane (bisphenol A), which is mainly used in the
    production of phenolic resins (Kirk-Othmer, 1980).

         The various applications of phenol as a percentage of total
    1981 consumption, in the USA and western Europe, are summarized in
    Table 4 (Kirk-Othmer, 1980). The data presented are in close
    agreement with the 1986 USA data reported by IARC (1989).

    Table 4.  Use of phenol in 1981 (% total consumption)a
    Production of                      USA                 West Europe

    Phenolic resins                    48                  36

    Bisphenol A(2,2-bis-1-
    hydroxyphenylpropane)              18                  17

    Caprolactam                        15                  28

    Other products                     19                  19

    Total                              100                 100

    a From: Kirk-Othmer (1980)

         Phenol was widely used in the 19th century for wound treatment
    and as an antiseptic and local anaesthetic. The medical uses of
    phenol today include incorporation into disinfectants, antiseptics,
    lotions, salves and ointments (IARC, 1989). Another medical
    application of phenol is its use as a neurolytic agent, applied in
    order to relieve spasm and chronic pain (Wood, 1978).

         In addition to the applications mentioned in section 3.2.2,
    phenol is used in the manufacture of paint and varnish removers,
    lacquers, paints, rubber, ink, illuminating gases, tanning dyes,
    perfumes, soaps and toys (IARC, 1989).


    4.1  Transport and distribution between media

         No data have been found concerning wet and dry deposition of
    phenol. Since phenol in air is present almost exclusively in the gas
    phase, dry deposition (by particle deposition) is expected to be
    negligible. Wet deposition may contribute to the disappearance of
    phenol from the atmosphere: when phenol was measured during seven
    episodes of rain in Portland, Oregon, USA, relatively high
    concentrations were found in the rain water (Leuenberger  et al.,

         Based on its relatively high solubility in water and the
    relatively low vapour pressure at room temperature, phenol is
    expected to end up largely in the water phase upon distribution
    between air and water. Consequently, transport from air to soil and
    water is likely (RIVM, 1986). Volatilization from dry near-surface
    soil should be relatively rapid (Howard, 1989).

         Theoretical deposition rates for phenol were estimated assuming
    a behaviour similar to SO2, and comparing with the rate of reaction
    of phenol with hydroxyl radicals (see below). Based on this
    comparison, it was concluded that most phenol in the atmosphere is
    degraded chemically, rather than transported (RIVM, 1986).

         Partition coefficient (Koc) values of phenol for two silt
    loams were reported to be 39 and 91 dm3/kg. Based on these Koc
    values, phenol would be expected to be highly mobile in soil, and
    therefore may leach to ground water (Howard, 1989). This was
    confirmed by Scott  et al. (1982) who found low adsorption of
    phenol to two sterile silt loams (pH 5.4, organic matter content 1.1
    and 3.6, respectively), as shown by Freundlich K values of 0.57 and
    1.19, respectively. Based on the pKa (log (1.28 x 10 -10)),
    phenol exists in a partially dissociated state in water and moist
    soils and, therefore, its transport and reactivity may be affected
    by pH (Howard, 1989). Upon measurement of the sorption and
    desorption of phenol from water to surface sediment (pH 6.21-6.35;
    organic matter content of fine fraction (< 2 µM) was 10.2%), phenol
    appeared to bind strongly to the soil. The estimated Koc was 2900
    dm3/kg (Isaacson & Frink, 1984). However, no correction was made
    for any degradation occurring during the experiments. The adsorption
    of phenol onto soil or microbial biomass may be decreased by the
    presence of phenol derivatives (Boyd, 1982; Selvakumar & Hsieh,

    1988). Phenol has been detected in ground water as a result of
    leaching (see section 5.1.2).

    4.2  Abiotic degradation

    4.2.1  Air

         Phenol may react in air with hydroxyl and NO3 radicals, and
    undergo other photochemical reactions to form dihydroxy-benzenes,
    nitrophenols, and ring cleavage products (Atkinson  et al., 1979;
    Bruce  et al., 1987). The half-life for phenol in air was found to
    be 4-5 h under photochemically reactive conditions in a smog chamber
    (Spicer  et al., 1985); this is in good agreement with the
    estimated half-life of phenol in air of 5 h based on its estimated
    reaction rate with hydroxyl radicals (RIVM, 1986). Howard (1989)
    reported an estimated half-life of 15 h for the reaction of phenol
    with hydroxyl radicals in air. The reaction of phenol with nitrate
    radicals during the night may be a significant removal process; a
    half-life of 15 min has been estimated at an atmospheric
    concentration of 2x108 nitrate radicals per cm3 (Howard, 1989).

         Phenol absorbs light in the region of 290-330 nm and therefore
    could photolyse (Howard, 1989).

    4.2.2  Water

         Phenols generally react in sunlit natural water via reaction
    with photochemically produced hydroxyl and peroxy radicals; typical
    half-lives were reported to be 100 and 19.2 h, respectively (Howard,

         Phenol was found to be oxidized to carbon dioxide in water
    under experimental conditions (temperature approximately 50 °C), in
    the presence of oxygen and sunlight, at a rate of 11% per 24 h
    (Knoevenagel & Himmelreich, 1976). It was reported to react with
    nitrate ions in dilute aqueous solutions to form dihydroxybenzenes,
    nitrophenols, nitrosophenol and nitroquinone, presumably by a
    radical mechanism involving hydroxyl and phenoxyl radicals (Niessen
     et al., 1988). Phenol has been found to react with nitrous acid in
    waste water to form cyanide (Adachi  et al., 1987), and to form
    chlorophenols in chlorinated drinking-water (Jarvis  et al., 1985)
    and p-benzoquinone in the presence of chlorine dioxide (Wajon  et
     al., 1982).

    4.3  Biodegradation

         Bacteria play a major role in the degradation of phenol in
    soil, sediment and water. The number of bacteria capable of
    utilizing phenol is usually a small percentage of the total
    population present in, for example, a soil sample (Hickman & Novak,
    1989). However, repeated phenol exposure may result in acclimation

    (the promotion of strains capable of utilizing phenol as food)
    (Young & Rivera, 1985; Colvin & Rozich, 1986; Shimp & Pfaender,
    1987; Wiggins & Alexander, 1988; Tibbles & Baecker, 1989).

         Phenol may be converted by bacteria under aerobic conditions to
    carbon dioxide (Southworth  et al., 1985; Ursin, 1985; Aelion  et
     al., 1987; Dobbins  et al., 1987; Aquino  et al., 1988), and
    under anaerobic conditions to carbon dioxide (Bak & Widdell, 1986;
    Tschech & Fuchs, 1987) or methane (Healy & Young, 1979; Ehrlich  et
     al., 1982; Young & Rivera, 1985; Fedorak & Hrudey, 1986; Fedorak
     et al., 1986). Benzoate, catechol,  cis-cis-muconate,
    ß-ketoadipate, succinate and acetate have all been identified as
    intermediates in the biodegradation of phenol (Paris  et al., 1982;
    Krug  et al., 1985; Fedorak  et al., 1986; Knoll & Winter, 1987).
    Some of the carbon derived from the degradation of phenol may be
    incorporated into the bacterial biomass (Chesney  et al., 1985).

         Phenol may be degraded in its free form as well as after
    adsorption onto soil or sediment, although the presence of sorbent
    reduces the rate of biodegradation (Shimp & Young, 1987; Knezovich
     et al., 1988).

         When phenol is the only carbon source, it can be degraded in a
    biofilm reactor with first-order kinetics at concentrations below
    about 20 µg/litre at 10 °C. The first-order rate constants are 3 to
    30 times higher than those of easily degraded organic compounds at
    100- to 1000-fold higher concentrations (Arvin  et al., 1991).
    Reported phenol degradation rates suggest rapid aerobic degradation
    in sewage (typically > 90% with an 8-h retention time), soil
    (typically complete biodegradation in 2-5 days), fresh water
    (typically complete biodegradation in < 1 day), and sea water
    (typically 50% in 9 days) (Howard, 1989). Anaerobic biodegradation
    is slower (Baker & Mayfield, 1980).

         The contribution of bacteria to the overall rate of degradation
    may be affected by a number of factors such as phenol concentration
    (Baker & Mayfield, 1980; Ursin, 1985; Hwang  et al., 1989),
    temperature (Baker & Mayfield, 1980; Bak & Widdell, 1986; Hwang  et
     al., 1986; Thornton-Manning et al, 1987; Gurujeyalashmi & Oriel,
    1989), sunlight (Hwang  et al., 1986), soil depth (Dobbins  et
     al., 1987; Federle, 1988), the presence of other nutrients
    required for bacterial growth (Rubin & Alexander, 1983; Fedorak &
    Hrudey, 1986; Rozich & Colvin, 1986; Thorton-Manning  et al.,
    1987), the presence of other pollutants (Southworth  et al., 1985;
    Hoffmann & Vogt, 1988; Wang  et al., 1988; Namkoong  et al., 1989)
    and bacterial abundance (Tranvik  et al., 1991).


    5.1  Environmental levels

    5.1.1  Air

         No data are available for background levels of phenol in air,
    away from emission sources. They are expected to be low (< 1 ng
    phenol/m3) (RIVM, 1986).

         Higher levels of phenol in air may be expected for urban areas,
    mainly due to traffic emissions. Urban phenol concentrations have
    been reported for Osaka, Japan (1-4 µg phenol/m3; Kuwata  et al.,
    1980), Nagoya, Japan (0.2-8 µg phenol/m3 with an average of 1.7 µg
    phenol/m3; Hoshika & Muto, 1979, 1980), Paris, France (0.7-8 µg
    phenol/m3; Hagemann  et al., 1978), and Portland, USA (0.22 to
    0.42 µg phenol/m3; Leuenberger  et al., 1985). Despite
    differences in analytical techniques, the first three series of
    measurements showed good agreement. The Portland results were lower,
    but came from air samples taken during rain periods; phenol was also
    detected in rain water (see section 5.1.2).

         Ambient air levels of phenol have been extensively monitored in
    the highly industrialized and urbanized Upper Silesia region of
    Poland (Sanitary Epidemiological Station, Katowice, 1991). Levels
    during 1990 ranged from 3.8 to 26.6 µg/m3, the highest values
    being in the areas of greatest industrial concentration.

         Hoshika & Muto (1979, 1980) reported a phenol level of
    approximately 190 µg/m3 "near" a phenolic resin factory (no
    details). Kuwata  et al. (1980) found phenol levels of 0.8-3.5
    mg/m3 in foundry emissions (no details).

         Based on limited data, median ambient atmospheric levels of
    phenol (based on estimated 24-h averages) were estimated by
    Brodzinsky & Singh (1982) to be 0.12 µg/m3 for urban/suburban
    areas (7 samples) in the USA (which is lower than reported above for
    several cities), and 104 µg/m3 (2-170 µg/m3) for source-
    dominated areas (83 samples) in the USA.

    5.1.2  Water and sediment

         Levels of phenol dissolved in rain water from Portland, USA,
    were found to range from 0.08 to 1.2 µg/litre and averaged above
    0.28 µg/litre; gas phase concentrations ranged from 220-410 ng/m3
    (Leuenberger  et al., 1985).

         Concentrations reported for surface water in the Netherlands
    were 2.5-6.5 µg/litre for two major rivers, 0.3-7 µg/litre for
    lakes, and 1.5 µg/litre for coastal waters (the given concentrations
    include other phenolic substances) (RIVM, 1986). Industrial rivers

    in the USA were reported to contain 0-5 µg/litre, but 3-24 µg/litre
    was reported for Lake Huron. Phenol was also detected in 2/100 raw
    water supplies in 1977 in the US EPA National Organics Monitoring
    Survey (Howard, 1989).

         Drinking-water levels of phenol in the USA have been reported
    to be around 1 µg/litre or otherwise below the detection limit
    (summarized by Howard, 1989). Phenol was detected (no quantitative
    data) in drinking-water in the USA from 5 out of 14 drinking-water
    plants surveyed and in Great Britain in 2 out of 4 sites (Fielding
     et al., 1981). Higher groundwater levels have been reported
    following industrial activity (e.g. 6.5-10 000 µg/litre in two
    aquifers 15 months after a coal gasification project; summarized by
    Howard, 1989). Phenol was detected at a maximum concentration of
    1130 mg/litre in nine wells in Wisconsin after a spill, and was
    detectable for at least 1.5 years after the spill (Delfino & Dube,

         Phenol was not detected in water samples from three areas in
    Japan analysed for an environmental survey; however, levels of
    0.03-0.04 mg/litre were detected in 3 out of 9 bottom sediment
    samples from the same regions (Fujii, 1978).

         Other sediment concentrations reported were 13 000 µg/kg in
    samples from Lake Huron, "not detected" in an unspecified industrial
    river in the USA, < 1000 µg/kg (dry weight) as the median
    concentration in 9% of sediment samples from 318 data points in the
    USA, and 10 µg/kg (dry weight) in samples collected 6 km from a
    wastewater treatment discharge zone in California (summarized by
    Howard, 1989).

         Phenol was detected in 63 out of 165 sediments from sampling
    areas in the Puget Sound region (Tetra Tech. Inc., 1986). Half the
    samples had a concentration of phenol below 40 µg/kg sediment (dry
    weight); the maximum level was 1700 µg/kg.

         Levels of phenol with means of 0.01-5.7 mg/litre (maximum up to
    53 mg/litre) have been reported in effluents from various industrial
    sources (summarized by Howard, 1989). Highest levels were associated
    with the iron and steel industry. Limited quantitative data from the
    VIEW Database (ATSDR, 1989) for ground water at hazardous waste
    sites indicated maximum levels of 2.48 to 85 000 µg/litre (average
    33 800 µg/litre, 6 data points).

         No data have been found indicating the presence of phenol in
    soil. Phenol is not likely to persist in soil because of rapid
    biodegradation (section 4.3) or transport to ground water or air
    (section 4.1).

    5.2  Occupational exposure

         Occupational exposure to phenol may occur during the production
    of phenol and phenol derivatives, during the production of phenolic
    resins and other products derived from phenol, during processing of
    the latter materials, and during a number of other activities.

    5.2.1  Production

         Personal air samples of workers involved in the production of
    phenol by the cumene process in the ex-USSR contained on average 5.8
    mg phenol/m3. For workers occupied in the production of phenol
    from chlorobenzene, the mean exposure level was 1.2 mg phenol/m3
    (Mogilnicka & Piotrowski, 1974). Values reported in the same
    publication for workers in two phenol resin-producing industries
    were 0.6-3 mg phenol/m3.

    5.2.2  Application of phenolic resins

         Occupational exposure during the processing of phenolic resins
    appears to be partly determined by the content of free phenol in the
    applied resin (Bollig & Decker, 1980; Ryser & Ulmer, 1980).

         In the wood industry, indoor phenol concentrations of 0.3 mg
    per m3 (Winkler, 1981) and 1.5 mg/m3 (range 0.8-2.6) (Gilli  et
     al., 1980) have been reported. Concentrations in the breathing
    zone of wood workers were 1.3-2.6 mg phenol/m3 (Gspan  et al.,
    1984). In another study, concentrations of < 0.04 to 1.9 mg
    phenol/m3 were found at plywood plants (Kauppinen  et al., 1986).

         In iron and steel foundries, average hourly phenol
    concentrations of 0.4-4.5 mg/m3 were reported in the manufacture
    of moulds or kernels (Schütz & Wolf, 1980). Phenol concentrations of
    1-4 mg/m3 were measured in a foundry in Osaka, Japan (Kuwata  et
     al., 1980). Local phenol concentrations were reported to be as
    high as 75-420 mg/m3 due to the thermal degradation of the resin.
    However, this effect of thermal degradation was not reflected in
    hourly concentrations measured during the foundry process: values of
    3-16 mg phenol/m3, with an average of 10 mg phenol/m3, were
    reported by Schütz & Wolf (1980), and a maximum hourly average of
    2.7 mg phenol/m3 was reported by Ryser & Ulmer (1980). (It is not
    known whether these results were obtained in personal or area air
    samples). Phenol concentrations during the operation of an electric
    furnace in a steel factory in Pueblo, Colorado, USA, were 0.04, 0.18
    and 0.20 mg/m3 in the vicinity of the furnace. General room air
    samples taken during operation of a grey iron foundry were below the
    detection limit (Gunter, 1987).

    5.2.3  Other occupational situations

         Exposure levels of 5-88 mg phenol/m3 have been reported for
    employees in the ex-USSR who quenched coke with waste water
    containing 0.3-0.8 g/litre phenol (Petrov, 1960).

         Measurements at coal gasification and liquefaction plants in
    the USA showed relatively low phenol concentrations (< 0.08 mg
    per m3) at various sites (Dreibelbis & Hawthorne, 1985).

         In a Japanese bakelite factory, area samples contained 0-12.5
    mg phenol/m3 (Ohtsuji & Ikeda, 1972).

         In a synthetic fibre factory in Japan, concentrations of 19 mg
    phenol/m3 were measured, whereas in a USA fibrous glass wool
    factory concentrations of 0.05-1.3 mg phenol/m3 were reported
    (Dement  et al., 1973; Ogata  et al., 1986).

         The concentrations of phenol in creosote vapour, analysed in
    seven creosote impregnation plants in Finland, ranged from < 0.1 to
    1.8 mg/m3 air (Heikkilä  et al., 1987). The highest exposures
    occurred during the cleaning of creosote warming chambers.

         During the dissection of cadavers by dental students, phenol
    breathing zone concentrations ranged from 5 to 19 mg phenol/m3.
    (The high phenol concentrations resulted from the applied embalming
    solution, in combination with inadequate ventilation) (Boiano,

    5.3  General population exposure

    5.3.1  Indoor air

         Borovik & Dmitriev (1981) found a maximal concentration of 0.02
    µg phenol/m3 in hospitals in the ex-USSR. It is, however, not
    clear from where the phenol originated; it may have been used as a
    disinfectant in these hospitals.

         No information has been found with regard to phenol
    concentrations in residential houses and apartments. Cigarette
    smoking must be considered as the most important potential source in
    dwellings. A distinction should be made between the main stream (the
    smoke inhaled by the smoker) and the side stream (produced by the
    smouldering cigarette itself). It was estimated that 0.01-0.22 mg
    phenol per cigarette was released in the mainstream, while the
    sidestream phenol content was 2.6 times higher. In the case of
    various Japanese cigarettes, 0.3-0.4 mg phenol was emitted into air
    during burning (Kuwata  et al., 1980). For an unventilated room of
    50 m3, the smoking of one cigarette would thus result in a phenol
    concentration of 6-8 µg/m3.

    5.3.2  Food and drinking-water

         Phenol is found in smoked meat and fish products. The wood
    smoke with which such products are treated contains, among other
    ingredients, a wide range of phenols and phenol ethers, which
    contribute significantly to the characteristic smoke aroma (smell
    and taste) of the product.

         Phenol is absorbed into the food products during smoking.
    Quantitative data, however, are scarce, since phenols are usually
    determined as a group. According to Toth (1982), the total phenol
    content of smoked sausage is 70 mg/kg; Bratzler  et al. (1969)
    found a content of 37 mg/kg in the outer layer of the product, and
    lower contents in the inner part. Luten  et al. (1979) determined a
    number of individual phenols in smoked herring and found a phenol
    content, depending on the duration of smoking, of approximately
    10-30 mg/kg. Potthast (1976, 1982) measured 2-18 mg/kg in smoked ham
    and liver sausage.

         If liquid smoke derivates are used in order to give a smoky
    flavour to fish and meat products, the end product also contains
    phenol. However, with regard to smell and taste aspects, phenol is
    not the most important phenolic compound from wood smoke. In this
    respect, methoxy and dimethoxy phenols are more important, together
    with aliphatic fatty acids and carboxyl compounds.

         Phenol may also enter food unintentionally by, for instance,
    contamination in transport or from packaging materials, or contact
    with other phenol-containing materials. However, these accidental
    cases would probably be detected and lead to non-acceptance by the
    consumer, owing to the conspicuous phenol smell and taste (see
    section 8.3 for odour and taste thresholds).

         Phenol has been found in botton pits fish from 5 sites in
    Commencement Bay in Tacoma, USA, at a maximum average of 0.14 mg/kg
    and an overall maximum of 0.22 mg/kg (Nicola  et al., 1987).

         Little information is available with respect to the occurrence
    of phenol in drinking-water. Surface and ground waters intended for
    the production of drinking-water in the Netherlands were reported to
    contain 1-9 µg phenol/litre (phenol index, including other phenolic
    compounds) (RIVM, 1986). Phenol was found in a domestic water supply
    in the USA at a level of 1 µg/litre (Ramanathan, 1984). Cases of
    drinking-water pollution with phenol have been reported in the UK
    and the USA; the phenol water concentrations were reported to be
    5-10 µg and 5-120 mg per litre, respectively (see section
    Chlorination of drinking-water may result in the formation of
    chlorophenols from phenol, which greatly adds to the objectionable
    smell and taste (Jarvis  et al., 1985).


         Phenol and conjugated metabolites of phenol occur naturally in
    animal and human tissue and can be detected in the urine, faeces,
    saliva and sweat. The body's production of phenol depends on the
    type of diet: a high protein or meat diet promotes phenol formation.

    6.1  Absorption

         Phenol is readily absorbed through all routes, such as the
    lungs, intact and abraded skin, and the gastrointestinal tract of
    both humans and animals (Von Oettingen, 1949; Deichmann & Keplinger,

    6.1.1  Animal uptake studies  Pulmonary

         There are no  in vivo data on absorption of phenol following
    inhalation exposure. However,  in vitro studies by Hogg  et al.
    (1981), using 14C-phenol with excised trachea-lung preparations
    and isolated perfused rat lung, demonstrated that phenol can be
    rapidly and efficiently absorbed in the lungs.  Dermal

         The extent of absorption of phenol through rabbit skin is more
    strongly influenced by the area of the skin exposed than by the
    concentration of the applied solution in water (Deichmann &
    Witherup, 1944; Liao & Oehme, 1980).

         In studies with the hairless mouse, phenol destroyed the
    stratum corneum (Behl  et al., 1983a). Similar effects were
    reported by Huq  et al. (1986) and Jetzer  et al. (1986).
    Absorption of phenol through thermally damaged mouse skin  in vitro
    was also reported to be greatly enhanced (Behl  et al., 1983b). In
    contrast, Deichmann  et al. (1952) observed that injury of the
    rabbit skin caused by phenol appeared to retard the rate of

         The permeability of mouse skin to phenol from aqueous solution
     in vitro increased with increasing temperature of the carrier
    solution (from 10 to 37 °C) (Jetzer  et al., 1988).

         Measurement of the permeation constant of phenol through
    hairless mouse skin at 37 °C  in vitro yielded a value of 18 800 ±
    3000 cm/h (Huq  et al., 1986; Jetzer  et al., 1986).  Intestinal

         When a single oral dose of 25 mg/kg body weight was
    administered to rats, pigs or sheep, more than 95% was absorbed (Kao
     et al., 1979).

          In vitro studies showed that aqueous solutions of phenol
    placed into ligated sections of the gastrointestinal tract had the
    fastest absorption rate in the colon, followed by the ileum. The
    absorption rate in the stomach was much slower (Deichmann &
    Keplinger, 1963).

    6.1.2  Human uptake studies  Pulmonary

         The retention of phenol in the bodies of eight human volunteers
    exposed to 6-20 mg/m3 by inhalation only for 8 h was 70%-80%
    during the course of the study (Piotrowski, 1971). Ohtsuji & Ikeda
    (1972) reported similar observations.  Dermal

         Human skin absorption of phenol vapour (5-25 mg/m3) occurs
    rapidly (Ruedemann & Deichmann, 1953). Fatal cases reflect the rapid
    rate of absorption of phenol through the skin (Turtle & Dolan, 1922;
    Duverneuil & Ravier, 1962; Hinkel & Kintzel, 1968; Lewin & Cleary,
    1982). The retention in eight human volunteers, exposed to phenol
    vapour at concentrations of 6-20 mg/m3, by skin only, for 6 h was
    70-80% (Piotrowski, 1971). Piotrowski (1971) proposed the following
    formula for calculating the absorption rate of phenol vapour through
    the skin: 

         A = (0.35)C

         where A is the amount of phenol absorbed in mg/h per unit area
    and C is the phenol air concentration in mg/m3.

         Concentrations of between 5 and 10% phenol denature epidermal
    protein, and this can partly prevent absorption. The phenol-protein
    complex is not stable and by dissociation of phenol the substance
    may exert its action over a period of time (Schmidt & Maibach,

         Phenol was detected in the urine of 4 out of 16 infants (2-5
    months) with seborrhoeic eczema who were skin-painted twice daily
    for 48 h with a commercial paint containing 4% (w/v) phenol and 8%
    (w/v) resorcinol (Rogers  et al., 1978). In adults, a single
    topical application of 4 µg phenol/cm2 on 13 cm2 of the ventral
    forearm, reportedly gave an absorption of 4.4% of the administered

    dose (Feldman & Maibach, 1970). The period of exposure and the
    concentration of phenol are both factors that determine the extent
    of absorption (Piotrowski, 1971; Roberts  et al., 1977;
    Baranowska-Dutkiewicz, 1981).

          In vitro studies have also shown that phenol from aqueous
    solutions (1% w/v) readily penetrates human skin (Roberts  et al.,
    1977, 1978). A value of 8200 cm/h was obtained as the permeation
    constant of phenol through human skin at 25 °C (Flynn & Yalkowsky,
    1972). In an  in vitro study with human abdominal skin, 10.9% of
    the applied dose was absorbed. This study showed an excellent
    qualitative, but a somewhat less accurate quantitative, agreement
    between the  in vivo and  in vitro skin absorption of 12 compounds
    (Franz, 1975).

    6.2  Distribution

         Phenol is rapidly distributed to all tissues in exposed

         In rabbits, 15 min after oral administration of 0.5 g
    phenol/kg, chemical analysis indicated that the liver contained the
    highest concentration of total phenol followed by the central
    nervous system, lungs and blood. After 82 min, phenol was fairly
    uniformly distributed over all tissues. The proportion of free to
    conjugated phenol changed with time, and, after 360 min, most of the
    phenol was conjugated (Deichmann, 1944).

         After a single oral administration of 14C-phenol (207 mg/kg)
    to rats, the highest concentration ratios between tissue and plasma
    were found in liver (42%), followed by spleen, kidney, adrenal,
    thyroid and lungs, with a peak tissue level occurring after 0.5 h
    (Liao, 1980; Liao & Oehme, 1981a).

         Highest tissue residues were found after 2 h in the kidneys and
    livers of mice and rats treated intravenously (Gbodi & Oehme, 1978;
    Wheldrake  et al., 1978; Greenlee  et al., 1981).

    6.3  Metabolic transformation

    6.3.1  Metabolite identification

         Studies employing several species have demonstrated that
    conjugation with glucuronic acid and sulfate are major metabolic
    pathways for phenol. Hydroxylation to hydroquinone and catechol also
    occurs (Williams, 1938, 1959; Garton & Williams, 1949; Bray  et
     al., 1952a,b,c; Parke & Williams, 1953).

          In vitro studies have shown the formation of 4, 4'-biphenol
    and diphenoquinone by neutrophils, activated leucocytes and by

    horseradish peroxidase following addition of phenol (Eastmond  et
     al., 1986).

         Phenol metabolism in rabbits was studied by Deichmann &
    Keplinger (1963). During the first 24 h following oral
    administration of a sublethal dose of 300 mg phenol/kg body weight,
    23% of the administered dose was recovered as exhaled carbon
    dioxide. Trace amounts of catechol and hydroquinone were also
    detected in the breath. Over the same period, 72% of the dose was
    excreted in the urine (48% of which was excreted as free and 52% as
    conjugated phenols), 1% was excreted in the faeces, 4% remained in
    the carcass, and trace amounts were exhaled.

         Oral administration of 14C-phenol (1.2 mg/kg) to rats
    resulted in at least 80% excretion in urine within 24 h, with 68% as
    phenyl sulfate and 12% as phenyl glucuronate (Edwards  et al.,

         A pronounced shift from sulfation to glucuronidation was
    observed in rats after increasing the phenol dose (Koster  et al.,
    1981). This observed shift is apparently due to a saturation of the
    overall sulfation process, rather than to a depletion of inorganic
    sulfate (Weitering  et al., 1979; Koster  et al., 1981; Koster,
    1982). A limited availability of 3-phosphoadenosine-5-phosphosulfate
    may account for the decreased proportion of phenol conjugation to
    sulphate at relatively high doses (Ramli & Wheldrake, 1981).
    Repeated administration of phenol, however, did not affect
    glucuronide synthesis in rats (Takemori & Glowacki, 1962).

         The pig has limited ability for phenol sulfation. The domestic
    cat lacks the ability for glucuronic acid conjugation of phenol. In
    cats, phenyl phosphate has been detected as a metabolite in small
    amounts, in addition to sulfate conjugates (Capel  et al., 1974;
    French  et al., 1974).

         Following oral administration of 14C-phenol (0.01 mg/kg) to
    three men, 90% of the dose was excreted in the urine within 24 h,
    mainly as phenyl sulfate (77%) and phenyl glucuronide. Small amounts
    of guinol sulfate and guinol glucuronide were also present (Capel
     et al., 1972b).

         Several investigators have confirmed the above-mentioned
    results using  in vitro methods (DeMeio & Arnolt, 1944; Capel  et
     al., 1972b; Shirkey  et al., 1979; Hogg  et al., 1981; Koster
     et al., 1981; Sawahata & Neal, 1983).

    6.3.2  Covalent binding to macromolecules

         Early pharmacokinetic studies (measuring distribution volumes)
    in dogs, pigs and goats suggested that tissue binding occurs (Oehme,
    1969). Further animal studies have indicated that phenol and/or its

    metabolites bind covalently to tissue protein, mainly in the liver
    (Bolt, 1977; Illing & House, 1980; Jergil  et al., 1982; Smart &
    Zannoni, 1984). Binding to rabbit bone marrow mitochondrial DNA in
    studies with isolated cells has also been reported (Rushmore  et
     al., 1984).  in vivo and  in vitro studies have demonstrated
    covalent binding of radiolabelled phenol to plasma proteins from
    humans, dogs, rats and trout (Liao, 1980; Liao & Oehme, 1981a,b;
    Judis, 1982; Schmieder & Henry, 1988). Reactive phenol metabolites
    formed by peroxidases bind readily to proteins (Eastmond  et al.,
    1986, 1987a) and DNA (Subrahmanyam & O'Brien, 1985).

    6.3.3  Location

         Quantitatively, the most important sites of phenol conjugation
    are the liver, lung and gastrointestinal mucosa. The relative roles
    played by these tissues depend on the route of administration and
    the dose.

         The liver is an important site of phenol metabolism. After
    direct administration of phenol into the hepatic circulation, the
    liver showed considerable first-pass metabolism in rats (Cassidy &
    Houston, 1980; Houston & Cassidy, 1982). Phenol-metabolizing enzymes
    have been detected in rabbit hepatic microsomes (Koop  et al.,

         Other tissues, such as lungs, intestines and kidneys, also play
    an important role in phenol metabolism (Quebbemann & Anders, 1973;
    Powell  et al., 1974; Houston & Cassidy, 1982). Phenol
    sulfotransferases, which catalyse phenol sulfation, occur in a
    variety of human tissues (intestinal wall, lungs, platelets, adrenal
    glands, brain, placenta, etc.) (Campbell  et al., 1987; Gibb  et
     al., 1987). After oral uptake of phenol, there is a very large
    first-pass metabolism in the intestines. The lungs also show
    considerable first-pass metabolism (as was established after direct
    administration into the pulmonary circulation of rats) (Cassidy &
    Houston, 1980; Houston & Cassidy, 1982). Due to saturation of
    hepatic enzymes, extrahepatic tissues play an increasing role in the
    conjugation of phenol as the dose of phenol increases; at doses
    higher than 5 mg/kg body weight, intestinal conjugation in rats
    exceeds the contribution of the hepatic and pulmonary enzymes
    (Cassidy & Houston, 1984).

         Myeloperoxidases isolated from human neutrophils and
    peroxidative enzymes from activated human leucocytes mediate the
    formation of reactive phenol metabolites including 4,4'-biphenol and
    diphenoquinone. Myeloperoxidase-mediated hydroxylation occurs in
    addition to hepatic cytochrome P-450 oxidation. In several species,
    myeloperoxidase activity has been reported in bone marrow, where it
    may play a role in phenol metabolism and toxicity (Eastmond  et
     al., 1986, 1987a; Subrahmanyam  et al., 1991).

    6.4  Elimination and excretion

         Urinary excretion is the major route of phenol elimination in
    animals and humans. The rate of excretion varies with dose, route of
    administration and animal species (Deichmann, 1944; Capel  et al.,
    1972a,b). Of 18 animal species studied by Capel  et al. (1972a,b),
    the 24-h urinary excretion of phenol was greatest in the rat (95% of
    the 25 mg/kg body weight oral dose) and the lowest in the squirrel
    monkey (only 31% of the dose). Liao & Oehme (1981a,b) reported a
    half-life of 4 h in rats.

         Five days after oral gavage with 14C-phenol (0.1 mg/kg body
    weight), only 0.3% of the applied dose was retained in rats (Freitag
     et al., 1985).

         Only minor amounts of unchanged phenol are excreted in exhaled
    air or in faeces (Deichmann & Keplinger, 1963). Less than 1% of an
    orally administered dose of 300 mg phenol/kg body weight to rabbits
    was found in the faeces after 24 h (Deichmann, 1944).

         Phenol conjugates may also be excreted in the bile of rats
    (4.6% of a 50 mg/kg dose) (Abou-el-Makarem  et al., 1967). It has
    been suggested that biliary excretion of phenol plays an important
    role when urinary excretion is impeded. Rats, whose kidneys were
    ligated, showed a marked increase in biliary excretion of phenol
    metabolites (Weitering  et al., 1979). Furthermore, it has been
    reported that phenol and its metabolites can undergo enterohepatic
    circulation in rats (Gbodi & Oehme, 1978).

         Urinary excretion of phenol in human volunteers exposed to
    phenol vapour via inhalation (chamber studies) or skin, occurred
    with an excretion rate constant of k = 0.2/h. For a one-compartment
    model, this corresponds to a half-life of approximately 3.5 h
    (Piotrowski, 1971).

    6.5  Biological monitoring

         The US ACGIH has listed a biological exposure index for phenol
    of 250 mg/g creatinine for end-of-shift urine samples (ACGIH, 1991).

         The excretion of phenol and phenol conjugates in the urine may
    be used as an index of exposure, but it should be noted that there
    are other causes that may lead to phenol excretion in the urine. One
    of these is benzene exposure; other possible significant sources are
    food and drugs (Docter & Zielhuis, 1967; Ikeda & Ohtsuji, 1969;
    Fishbeck  et al., 1975; Paradowski  et al., 1981). Elevated
    urinary phenol excretion is thus not a specific index of exposure to
    phenol. Furthermore, the large range of "normal" urine values
    (phenol concentrations have been found to vary from 0.5 to 81.5
    mg/litre) (Deichmann & Schafer, 1942; Docter & Zielhuis, 1967;
    Piotrowski, 1971; Gspan  et al., 1984; Pekari  et al., 1992) would

    appear to limit the usefulness of urinary phenol excretion as an
    accurate index of low occupational exposure levels. 

         In volunteers, after a single 8-h exposure to phenol vapour 
    concentrations of up to 6.8 mg/m3, the phenol excretion in urine 
    increased up to a maximum of 100 mg total phenol/litre (Piotrowski, 
    1971). In workers occupationally exposed to 10 mg phenol/m3, 
    concentrations in urine of up to 262 mg/litre were reported 
    (Ohtsuji & Ikeda, 1972). However, another recent study, using more 
    specific methods of analysis, showed good correlation (R=0.91) between 
    exposure levels in the range 5-17 mg/m3 and the total concentration 
    of phenyl sulfate and phenyl glucuronide in the urine at the end of the
    workshift (Ogata  et al., 1986).


    7.1  Single exposure

    7.1.1  LD50 values

         After oral administration of phenol to mice, rats and rabbits,
    LD50 values ranged from 300-600 mg phenol/kg body weight. No
    LC50 values have been reported in the published literature.
    However, after inhalation of 900 mg phenol/m3 by rats for 8 h, no
    deaths were observed. The dermal LD50 (by occlusive and
    non-occlusive techniques) was 670 mg/kg body weight for rats and
    850-1400 mg phenol/kg body weight for rabbits. LD50 values for
    intraperitoneal injection were in the range of 127-223 mg phenol/kg
    body weight for rats.

         A summary of LD50 values is given in Table 5.

    7.1.2  Effects

         The acute lethality of phenol, associated with exposure to high
    concentrations, is generally attributed to a depressing effect on
    the central nervous system (see also section 7.8.1). The clinical
    effects of phenol poisoning are independent of the route of
    administration. Reported symptoms include neuromuscular
    hyperexcitability, including twitching and severe convulsions. Heart
    rate at first increases, then becomes slow and irregular. Blood
    pressure at first increases slightly, then falls markedly.
    Salivation, marked dyspnoea and a decrease in body temperature are
    also among the effects reported (Deichmann & Witherup, 1944; Von
    Oettingen & Sharples, 1946; Farquharson  et al., 1958; Ernst  et
     al., 1961; Deichmann & Keplinger, 1963; Oehme & Davis, 1970;
    Pullin  et al., 1978; Liao & Oehme, 1980; Reid  et al., 1982).

         After oral ingestion, the mucous membranes of the throat and
    oesophagus showed swelling, corrosion, and necrosis, with
    haemorrhages (Deichmann & Keplinger,1963).

         In a study by Schlicht  et al. (1992), female Fischer-344 rats
    were administered 0, 12, 40, 120 or 224 mg phenol/kg body weight by
    gavage in a water vehicle. Animals were examined for clinical signs,
    and neurotoxicity and systemic (liver, kidney, adrenal and thymus)
    effects, 4-20 h after treatment. Tremors were observed 1-2 min after
    dosing in the two highest dose groups. The pupil response to light
    (miosis) was significantly inhibited at all dose levels at 24 h
    after exposure. Locomotor activity was reduced at 224 mg/kg. At this
    dose level, 2/6 animals had hepatocyte necrosis, 4/6 had renal
    vascular stasis and 4/6 had necrosis of the thymus. At 120 mg/kg,
    liver necrosis was present in 1/7 animals, as was necrosis of the
    thymus gland.

        Table 5.  Acute animal toxicity of phenol LD50 values
    Species    Route of         LD50 values    Vehicle       Reference
               administration   (mg/kg body

    Mouse      oral             300                          Von Oettingen &
                                                             Sharples (1946)

    Mouse      oral             427                          Kostovetskii &
                                                             Zholdakova (1971)
    Rat        oral             340-530        2-7% in
                                               water         Deichmann &
                                                             Witherup (1944)

    Rat        oral             512                          Kostovetskii &
                                                             Zholdakova (1971)

    Rat        oral             445-520        water         Thompson & Gibson

    Rat        oral             400            water         Schlicht  et al.

    Rat        dermal           670            undiluted     Conning & Hayes
                                (570-780)                    (1970); Brown et al.

    Rat        intraperitoneal  127-223        water or      Thompson & Gibson

    Rabbit     oral             400-600        2-7% in       Deichmann &
                                               water         Witherup (1944)

    Rabbit     dermal           850                          Flickinger (1976)

    Rabbit     dermal           1400                         Vernot  et al. (1977)
             In various animal species, inhalation of phenol adversely
    affected the lungs, causing hyperaemia, infarcts, bronchopneumonia,
    purulent bronchitis and hyperplasia of the peribronchial tissues
    (Von Oettingen, 1949).

         Sensory irritation was measured in mice by the Alarie assay. A
    50% decrease in respiratory rate (RD50) was found at 638 mg
    phenol/m3 (De Ceaurriz  et al., 1981).

         Ocular and nasal irritation, tremors and incoordination were
    reported in rats exposed via inhalation to 906 mg/m3 for 8 h
    (Flickinger, 1976).

         Other pathological abnormalities induced by phenol by various
    routes of administration included demyelination of nerve fibres (see
    also section 7.8.1), myocardial degeneration and necrosis (Deichmann
    & Keplinger, 1963; Liao & Oehme, 1980). Kidney damage (vacuolization
    and enlargement of cells) and liver damage (e.g., enlargement of
    hepatic cells) were also observed (Oehme & Davis, 1970; Coan  et
     al., 1982). Urine was usually dark or "smoky" in appearance,
    probably due to oxidation products of phenol (Solliman, 1957).

    7.2  Short-term exposure

    7.2.1  Oral exposure

         In a study by Schlicht  et al. (1992), groups of eight female
    Fischer-344 rats received oral doses of phenol in a water vehicle of
    0, 4, 12, 40 or 120 mg/kg body weight daily for 14 days. Tremors
    were apparent only after the first dose at the highest level.
    Exposure to 120 mg/kg per day was lethal to all rats within 11 days.
    The pupil response (miosis) was decreased one day after the last
    dose for all but the highest surviving dose group (the incidences
    were 100%, 50%, 62% and 76% for the 0, 4, 12 and 40 mg/kg groups,
    respectively). Locomotor activity was not affected after the 4th,
    9th or 14th dose. No hepatic effects were observed at 40 mg/kg per
    day, while 3/8 animals had renal vascular stasis. There were no
    histological effects at 12 mg/kg per day. At 40 mg/kg per day, the
    pathological changes in the kidneys included two animals with
    tubular degeneration in the papillar region, and one with protein
    casts in the tubules. The pathological report attributed these
    findings to decreased vascular perfusion (MacPhail, personal
    communication to the IPCS).

         Rats were administered, by gavage, 20 daily doses of 10, 50 or
    100 mg phenol/kg body weight. At necropsy, slight effects on liver
    and kidneys were reported at 100 mg phenol/kg body weight (Dow
    Chemical Company, 1976).

         Rats receiving 50 or 100 mg phenol/kg body weight, by gavage,
    over a 6-month period (135 doses, presumably daily, 5 days/week)
    were reported to show slight to moderate kidney damage.
    Administration of 100 mg phenol/kg body weight apparently resulted
    in slight liver changes (Dow Chemical Company, 1976).

         In a range-finding study, carried out prior to a long-term
    carcinogenicity study, mice and rats were provided with tap water
    containing 0, 100, 300, 1000, 3000 or 10 000 mg phenol/litre for 13
    weeks. Mean body weight gain was decreased only in mice and rats
    receiving 10 000 mg phenol/litre (NCI, 1980). In these

    drinking-water studies, the highest daily doses were calculated to
    be approximately 2000 mg phenol/kg body weight for mice and 1000 mg
    phenol/kg body weight for rats.

         Phenol was provided to rats in drinking-water for 12 months at
    0, 800, 1200, 1600, 2000 and 2400 mg phenol/litre. Depressed weight
    gain was observed in rats receiving doses > 2000 mg/litre. The
    corresponding daily dose was calculated by the authors of the study
    to be > 200 mg/kg body weight (Deichmann & Oesper, 1940).

    7.2.2  Dermal exposure

         In a study by Deichmann  et al. (1950), rabbits were exposed
    to 1.18-7.12% phenol in water (64-380 mg phenol/kg body weight) for
    5 h/day, 5 days/week, for 18 days. Dose-related systemic effects
    (tremors, death) were observed in rabbits exposed to > 2.37%
    phenol (130 mg phenol/kg body weight), while skin irritation
    (hyperaemia, tissue necrosis) occurred at doses of > 3.56% phenol
    (190 mg phenol/kg body weight). This effect was particularly
    apparent when the application sites were bandaged.

    7.2.3  Inhalation exposure

         No studies reported or conducted according to contemporary
    standards were available.

         In a study by Deichmann  et al. (1944), rats, rabbits and
    guinea-pigs were exposed to concentrations of 100-200 mg phenol
    vapour/m3, 7 h/day, for 5 days/week. Rats exposed for a period of
    74 days did not show any gross or microscopic evidence of injury.
    Rabbits survived a 3-month exposure but, at autopsy, lung and heart
    damage and indications of liver and kidney damage were found.
    Guinea-pigs were the most susceptible. Five out of twelve died after
    12 days of exposure, and the remaining seven were killed after 29
    days of exposure. Prior to death, guinea-pigs showed weight loss,
    respiratory difficulties, and signs of paralysis. At autopsy, there
    was evidence of acute lobular pneumonia, vascular damage, and
    hepatic and renal damage; the total (free and conjugated) phenol
    content of the blood was 14 mg/litre. The rabbits had similar, but
    less severe, symptoms.

         Groups of 10 monkeys, 50 rats and 100 mice were exposed to 19
    mg phenol/m3, 8 h/day, 5 days/week for 90 days. Concurrent control
    groups were exposed to fresh air only. No deaths occurred and there
    was no reduction in weight gain of treated animals. There were no
    statistically significant adverse effects observed when the animals
    were assessed by a stress test involving swimming performance. A
    range of clinical chemistry, haematology and urinalysis parameters
    were not affected by exposure to phenol. Routine histology was
    performed on the liver, lungs, kidneys, brain and heart. The results
    of the percentage of animals showing evidence of "pathological

    change" indicated effects in the liver and kidneys of exposed
    animals. However, the author of the study concluded that no clinical
    or pathological changes occurred that were of toxicological
    importance. It is not clear if the upper respiratory tract was
    examined in this study in order to look for evidence of irritation
    (Sandage, 1961).

         Continuous exposure to 100 mg phenol/m3 for 15 days
    significantly affected the central nervous system of rats, as was
    demonstrated by their performance in the "tilted plane" test. Plasma
    levels of potassium, magnesium, lactate dehydrogenase, aspartate
    aminotransferase (ASAT), alanine aminotransferase (ALAT) and
    glutamate dehydrogenase were elevated. Haemoglobin, haematocrit, and
    plasma sodium, calcium and chloride levels were unaffected (Dalin &
    Kristofferson, 1974).

    7.2.4  Subcutaneous exposure

         Subcutaneous exposure to phenol was studied principally to
    obtain information about neurological or haematopoietic effects (see
    sections 7.8.1 and 7.8.2). No other effects were reported.

    7.2.5  Ear exposure

         Instillation of phenol (form and amount not specified) into the
    inner ear round window of Sprague-Dawley rats caused morphological
    damage to the organ of Corti in the basal coil. The outer hair cells
    appeared to be more sensitive to phenol than the inner hair cells,
    which were mostly intact. As a result of the damage, impairment of
    inner ear function was noted (as determined by auditory brain stem
    recordings) which was regressive for lower sound frequencies, but
    appeared to be permanent for higher frequencies (Anniko  et al.,

    7.3  Skin and eye irritation; sensitization

         Local damage to the skin, following exposure to phenol, was
    found to include erythema, inflammation, discoloration, eczema,
    papillomas and necrosis (Deichmann, 1949; Deichmann  et al., 1950;
    Conning & Hayes, 1970; Pullin  et al., 1978). For example, in
    rabbits, 0.5 g phenol, moistened with physiological saline, produced
    necrosis of both the intact and abraded skin (Flickinger, 1976).

         Solutions of 10-14% (v/v) phenol in water have been reported to
    cause transient delayed erythema (after 0.5-5 h) and acute vascular
    permeability, as assessed by exudation of intravenously injected
    Evans blue, in guinea-pigs after dermal treatment for 1 min (Steele
    & Wilhelm, 1966).

         In one study, an increase in ear thickness was used as an index
    of skin irritation (inflammation). Maximal responses to phenol were

    observed one hour after application of 1-2 mg phenol to the ear of
    female ICR mice. Significant thickening could still be detected 6
    weeks after exposure (Patrick  et al., 1985).

         When phenol, in glycerine dilutions down to 10% or 5% aqueous
    solutions, was applied to the rabbit eye, severe damage (complete
    destruction to opaque corneas) was seen. Immediate water irrigation
    was very effective in preventing the opacity. A delay of 10 seconds
    reduced this effectiveness (Murphy  et al., 1982).

         Fourteen days after the application of 0.1 g phenol to the
    rabbit eye, all eyes exhibited keratoconus and pannus formation
    (Flickinger, 1976).

         Phenol gave negative results in a Magnussen and Kligman skin
    sensitization test (Itoh, 1982).

    7.4  Long-term exposure

         No adequate data are available. Studies on carcinogenicity are
    presented in section 7.7.

    7.5  Reproduction, embryotoxicity and teratogenicity

    7.5.1  Reproductive toxicity

         No adequate studies conducted according to current protocols
    are available.

         Heller & Pursell (1938) exposed rats to 100-12 000 mg
    phenol/litre drinking-water, corresponding to calculated approximate
    daily oral doses of 10-1200 mg phenol/kg body weight. General
    appearance, growth and fecundity were normal for rats exposed to
    100-1000 mg/litre for five generations and to 3000 or 5000 mg/litre
    for three generations. Stunted growth was noted in the offspring of
    rats exposed to 7000 mg/litre. Many of the offspring died at levels
    of 8000 mg/litre because of maternal neglect. At 10 000 mg/litre,
    the offspring died at birth, and at 12 000 mg/litre there was no

    7.5.2  Embryotoxicity/teratogenicity  In vivo studies

         Phenol was evaluated for maternal and developmental toxicity in
    timed-pregnant Sprague-Dawley rats (20-22 confirmed pregnancies per
    group). Distilled water (vehicle) or phenol (30, 60 or 120 mg/kg per
    day) was administered daily by gavage in a volume of 5 ml/kg of body
    weight throughout the period of major organogenesis (gestational
    days 6-15). Dams were weighed on the day of sperm detection
    (gestational day 0), prior to daily dosing, and at termination

    (gestational day 20); observations for clinical signs of toxicity
    were conducted during the treatment period. At termination
    (gestational day 20), maternal liver weight, gravid uterine weight
    and status of uterine implantation sites (i.e. number of implants,
    resorptions, late fetal deaths and live fetuses) for each dam were
    recorded. Each live fetus was weighed, sexed and examined for
    external morphological abnormalities. Visceral examination of each
    fetus was performed using a fresh tissue dissection method;
    approximately one-half of the fetal heads from each litter were
    fixed (Bouins' solution) and sectioned free-hand for examination of
    internal structures; carcasses (one-half without heads) were cleared
    and stained with Alizarin Red S prior to skeletal examination. All
    control and phenol-treated dams survived to scheduled sacrifice, and
    no distinctive treatment-related signs of toxicity were noted.
    Pregnancy rates at termination were high (95-100% per group) and no
    litters were totally resorbed, so that a total of 20-22 live litters
    per group (268-293 fetus per group) was available for examination.
    No significant dose-related changes were noted for the following
    end-points: maternal body weight (gestational day 0, 6, 11, 15 or
    20), maternal body weight gain (treatment period, gestational period
    or gestational period corrected for gravid uterine weight), maternal
    liver weight, gravid uterine weight, prenatal mortality, live litter
    size or incidence of morphological abnormalities (malformations or
    variations). However, average fetal body weight per litter was
    significantly reduced at the high-dose (93% of average control
    weight) (Jones-Price  et al., 1983a).

         In a study by Kavlock (1990), phenol was administered by oral
    gavage to groups of Sprague-Dawley rats on day 11 of gestation (day
    1 : sperm plug) at 0, 100, 333, 667 and 1000 mg phenol/kg body
    weight. The vehicle used in this study was a 4:4:1:1 mixture of
    water, Tween 20, propylene glycol and ethanol. Maternal toxicity
    (decreased weight gain) was seen at the two highest doses. Offspring
    viability and growth were not affected up to postnatal day 6,but
    hind limb paralysis was observed in some offspring in the two
    highest dose groups.

         In a screening assay, groups of 17-21 Fischer-344 rats received
    0, 40 or 53.3 mg phenol/kg body weight by gavage in water on
    gestation days 6-15. There were no significant effects on maternal
    body weight gain. One of 15 pregnant females resorbed the entire
    litter at 40 mg/kg and 2 of 16 did so at 53.3 mg/kg (there were no
    similar effects in 153 control litters in the study). All three
    females had severe respiratory syndromes (rales and dyspnoea). One
    high-dose female with symptoms of respiratory toxicity delivered a
    low weight litter that had poor viability. Kinked tails were present
    in 2 of 4 surviving pups in that litter. Litter size on postnatal
    days 1 and 6 was significantly reduced at 53.3 mg/kg but not at 40
    mg/kg. There were no effects on pup body weights on postnatal days 1
    or 6 (Narotsky & Kavlock, 1993).

         Phenol was evaluated for maternal and developmental toxicity in
    timed-pregnant Swiss albino (CD-1) mice (22-29 confirmed pregnancies
    per group). Distilled water (vehicle) or phenol (70, 140 or 280
    mg/kg per day) was administered daily by gavage in a volume of 10
    ml/kg of body weight throughout the period of major organogenesis
    (gestational days 6-15). Dams were weighed on the day of vaginal
    plug detection (gestational day 0), prior to daily dosing
    (gestational days 6-15), and at termination (gestational day 17);
    observations for clinical signs of toxicity were conducted during
    the treatment period. Evaluation of maternal and developmental
    end-points at termination (gestational day 17) were the same as for
    rats (see description from the study by Jones-Price  et al., 1983a,
    above). Toxicity observed at the high-dose level included 11%
    mortality (4/36 treated females), clinical signs (especially tremor
    and ataxia), reduced maternal body weight (gestational day 17),
    reduced maternal body weight gain (treatment period, gestational
    period and gestational period corrected for gravid uterine weight),
    and a trend only toward reduced maternal liver weight. Pregnancy
    rates at termination ranged from 71 to 84%; no litters were totally
    resorbed so that 22-29 live litters (214-308 fetuses) were available
    for examination. No dose-related changes were noted for prenatal
    mortality, live litter size or incidence of morphological
    abnormalities, except for an apparent increase in cleft palate
    (8/214 fetuses in the high dose versus 0/308 among controls). (It
    should be noted that cleft palate is a malformation to which the
    CD-1 mouse is predisposed under conditions of maternal stress).
    Average fetal body weight per litter was significantly reduced (82%
    of average control weight) in the highest dose group (Jones-Price
     et al., 1983b).

         In a study by Minor & Becker (1971), groups of Sprague-Dawley
    rats were given 20, 63, or 200 mg phenol/kg body weight
    intraperitoneally on days 9-11 or 12-14 of gestation. Fetal body
    weight was reduced in the highest dose group treated on days 12-14.
    No gross anomalies were observed, and intrauterine death was not
    increased at any dose level.  In vitro studies

         In the chick embryotoxicity screening test (CHEST), 130
    substances were tested. For each compound, 120 selected White
    Leghorn Fowl embryos, aged 1.5, 2, 3 and 4 days of incubation, were
    used. Phenol did not exhibit embryotoxic properties in this test up
    to 100 µg, and was one of the least embryotoxic compounds tested
    (Jelinek  et al., 1985).

         In a study by Oglesby  et al. (1992), phenol was added to
    cultures of five rat embryos on gestational day 10 at
    concen-trations of 0 to 100 µg/ml. Embryos were examined 42 h later
    for viability, growth and morphology. Viability was not affected at
    any concentration, but a low incidence of tail defects was observed

    at 100 µg/ml, and embryonic growth was decreased at 75 and 100
    µg/ml. When hepatocytes isolated from pregnant rats were co-cultured
    with the embryos, the toxicity to the embryos was increased. Tail
    defects were observed at 25 and 50 µg/ml, and growth was reduced at
    these concentrations. Without the presence of hepatocytes, phenol
    was the least toxic of 13 para-substituted phenols tested in this
    system; however, it was the only one which became more embryotoxic
    when hepatocytes were present.

         When phenol was added to cultures of human embryonic palatal
    mesenchyme cells, cell growth was 50% inhibited at a concentration
    (IC50) of 0.8 mM (78 µg/litre) (Pratt & Willis, 1985).

    7.6  Mutagenicity and related end-points

         Data on mutagenicity and related end-points are summarized in
    Tables 6, 7, 8 and 9, respectively.

    7.6.1  Mutagenicity studies  Bacterial systems

         Phenol has been tested for mutagenicity by a number of authors
    in various strains of  Salmonella typhimurium and was shown to be
    reproducibly negative, both with and without metabolic activation
    (Epler  et al., 1979; Gilbert  et al., 1980; Rapson  et al.,
    1980; Pool & Lin, 1982; Haworth  et al., 1983). A positive effect
    was observed in strain TA98 in the presence of an exogenous
    metabolic activation system in a study employing a modified culture
    medium (Wild  et al., 1980; Gocke  et al., 1981).

         A positive effect was reported for phenol in a fluctuation test
    with strain TA100 after metabolic activation, but no data were given
    on toxicity (Koike  et al., 1988; abstract). A positive result was
    reported in a mutation test with  Escherichia coli B/Sd-4; however,
    the applied dose levels were highly toxic (Demerec  et al., 1951).  Non-mammalian eukaryotic systems

         Negative data were obtained in the absence of exogenous
    metabolic activation with the eukaryotic microorganism
     Saccharomyces cerevisiae. At high doses and in the presence of an
    activation system, a positive result was obtained (Cotruvo  et al.,
    1977). Phenol induced mitotic segregation in  Aspergillus nidulans
    (Crebelli  et al., 1987).

        Table 6.  Tests for genotoxicity in bacteria

    Species           Strain       Measured end-point    Test conditions            Metabolic       Resultsb       Reference

    Escherichia coli  Sol-4        reverse mutation      0.1-0.2%; 3-24 h           -               +              Demerec et al.
                                                         (survival less than 2%)                                   (1951)

                      AB1899 nm    filamentation         10-500 µg/ml; 3-4 h                        -              Nagel et al.

    Salmonella        TA100        reverse mutation      fluctuation test           -               -              Koike et al.
    typhimurium                                          0-500 ng/well              + (rat)         + (no data     (1988)
                                                                                                    on toxicity)

                      TA98         reverse mutation      1000-fold concentration    + and -         -              Epler et al.
                      TA100        range in DMSOc        (1979)

                      TA1535       reverse mutation      0-100 µg/plate             -               -              Gilbert et al.
                      TA1538       reverse mutation      0-50 µg/plate              -               -

                      TA98         reverse mutation      0-3333 µg/plate in         -               -              Haworth et al.
                      TA100                              DMSO; preincubation        + (rat)         -              (1983)
                      TA1535                                                        + (hamster)     -
                      TA98         reverse mutation      0-3333 µg/plate in         -               -              Haworth et al.
                      TA100        preincubation H2O;                               + (rat)         -              (1983)
                      TA1535                                                        + (hamster)     -

                      TA98         reverse mutation      0.5-5000 µg/plate in       + and - (rat)   -              Pool & Lin
                      TA100        DMSO (5000 µg toxic)                                                            (1982)

    Table 6 (contd).

    Species           Strain       Measured end-point    Test conditions            Metabolic       Resultsb       Reference

                      TA100        reverse mutation      0.1-1000 µg/plate          -               -              Rapson et al.

                      TA98         reverse mutation      0-100 µmol/plate (99.5%    -               -              Wild et al.
                                                         purity with 0.15% + (rat)  +                              (1980)
                                                         cresols as main impurity,
                                                         non-standard media)

    a  + = present; - = absent
    b  + = positive; - = negative
    c  DMSO = dimethyl sulfoxide

    Table 7.  Tests for genotoxicity in non-mammalian eukaryotic systems

    Species          Strain     Measured end-point         Test conditions           Metabolic      Resultsa   Reference


     Saccharomyces   D3         mitotic recombination      10-5, 10-3 dilution of    -              -          Cotruvo et al.
     cerevisiae                                            phenol in saline          + (rat)        +          (1977)

     Aspergillus                mitotic segregation        5-20 mM                   -              +          Crebelli et al.
     nidulans                                                                                                  (1987)


     Drosophila      Oregon-R   SLRLb                      phenol vapour 24 h;                      -          Sturtevant
     melanogaster                                          0.2, 0.25, 0.5% in                       -          (1952)
                                                           saline, injection

                                                           0.01, 0.1, 1.2% in                       -
                                                           Holtfreter solution;
                                                           vaginal douch

                     Berlin K   SLRL                       50 nM in 5% saccharose;                  -          Wild et al.
                                                           feeding, 3 broods F1                                (1980); Gocke
                                                           generation                                          et al. (1981)

                                                           injection                                -          Woodruff et al.


     Salmo gairdneri            chromosomal aberrations    0.3-0.6 µl/litre, 72 h                   +          Al-Sabti (1985)

    a  + = positive; - = negative
    b  SLRL = sex-linked recessive lethal mutations

    Table 8.   In vitro phenol genotoxicity in mammalian cells

    Species          Cell type        End-pointa           Conditions                Activationb    Resultc    Reference

    Chinese hamster  CHO-WBL          CA                   500-800 µg/ml             -              -          Ivett et al. (1989)

                                                           2000-3000 µg/ml           + (rat)        +

    Chinese hamster  V79 lung         forward mutation     0-500 µg/ml               + (mouse)      +          Pashin & Bakhitova
                                      HPRT                 (500 µg/ml toxic)                                   (1982)

    Chinese hamster  CHO-WBL          SCE                  300-400 µg/ml             -              +          Ivett et al. (1989)

                                                           2000-3000 µg/ml           + (rat)        +

    Chinese hamster  V79 lung         intercellular        not reported              -              -          Chen et al. (1984)

                     V79 lung         intercellular        250 µg/ml                 -              -          Malcolm et al. (1985)

                     V79 lung         intercellular        10-75 µg/ml               -              -          Bohrman et al. (1988)

    Mouse            L5178Y lymphoma  forward mutation     600-1800 µg/ml            + and -        ?          McGregor et al.
                                      TK                                                                       (1988)

                     L5178Y           forward mutation     180-890 µg/ml             -              +          Wangenheim &
                                                           (530 µg/ml toxic)                                   Bolcsfoldi (1988)

                                                           5.6-41 µg/ml              + (rat)        +
                                                           (20 µg/ml toxic)

    Mouse            L5178Y           DNA synthesis        9.4-940 µg/ml             -              +          Pellack-Walker
                                      inhibition                                                               et al. (1985)

                     L5178Y           DNA strand breaks    16-470 µg/ml              -              -          Garberg et al.
                                                           16-470 µg/ml              + (rat)        +          (1988)

    Table 8 (contd).

    Species          Cell type        End-pointa           Conditions                Activationb    Resultc    Reference

                     L5178Y           DNA strand breaks    94 µg/ml                  -              -          Pellack-Walker & Blumer

    Human            T-lymphocytes    SCE                  0.47-282 µg/ml            -              +          Erexson et al. (1985)

                     lymphocytes      SCE                  188 µg/ml                 -              -          Jansson et al. (1986)

                     lymphocytes      SCE                  1.7-470 µg/ml             + (rat)        +          Morimoto & Wolff
                                                           (470 µg/ml toxic)                                   (1980)

                     lymphocytes      SCE                  282 µg/ml                 + (rat)        +          Morimoto et al.

    Human            fibroblast       DNA repair           0.094-9400 µg/ml                         +          Poirier et al. (1975)

                     HeLa             DNA synthesis        188 µg/ml                 + (rat)        +          Painter & Howard
                                      inhibition                                                               (1982)

                     WI-38            DNA synthesis        0.094-9400 µg/ml                         +          Poirier et al. (1975)

    a  CA = chromosome aberrations; HPRT = hypoxanthine guanine phosphoribosyl transferase locus; TK = thymidine kinase locus;
       SCE = sister chromatid exchange
    b  - = absent; + = present; 
    c  - = negative; + = positive

    Table 9.  Phenol genotoxicity in in vivo mammalian systems

    Species/Strain    Measured end-point             Test conditions                     Remarks                Resultsa    Reference
                                                     (sampling times)

    Mouse/CD-1        micronuclei in bone            265 mg/kg, oral                     bone marrow            +           Ciranni et al.
                      marrow                         (0, 18, 24, 42 or 48 h)             depression                         (1988a)

    Mouse/CD-1        micronuclei in maternal bone   gestation day 13, 265 mg/kg,        maternal bone marrow   +           Ciranni et al.
                      marrow and fetal liver         oral (15, 18, 24, 30, 36 or 40 h)   depression                         (1988a)

    Mouse/CD-1        micronuclei in bone            250 mg/kg, oral (30 h)              convulsive seizures    -           Gad-El Karim et
                      marrow                                                                                                al. (1986)

    Mouse/CD-1        micronuclei in bone            265 mg/kg, i.p.                     bone marrow            +           Ciranni et al.
                      marrow                         (18, 24, 42 or 48 h)                depression                         (1988a)

    Mouse/CD-1        micronuclei in bone            40, 80 or 160 mg/kg, i.p.           no bone marrow         -           Barale et al.
                      marrow                         (18 h)                              depression                         (1990)

    Mouse/NMRI        micronuclei in bone            47, 94 or 188 mg/kg, i.p.           no information on      -           Gocke et al.
                      marrow                         0, 24 h (30 h)                      toxicity                           (1981)

    Mouse/Porton      chromosomal aberrations in     2 ml of 0.08, 0.8 or 8 mg/litre                            +           Bulsiewicz (1977)
                      spermatogonia, primary         solution, oral, daily for five
                      spermatocytes                  generations

    Rat/Sprague-      chromosomal aberrations in     72-180 mg/kg, i.p.                  LD1-LD30, no change    -           Thompson &
     Dawley           bone marrow                    300-510 mg/kg, oral (20 h)          in mitotic index                   Gibson (1984)

    Rat/Sprague-      DNA strand breaks (alkaline    7.9, 26 or 79 mg/kg, i.p. (2.6      -                                  Skare & Schrotel
     Dawley           elution in rat testis)         or 24 h) 4, 13.2 or 39.5 mg/kg,                                        (1984)
                                                     i.p. for 5 days

    a  + = positive; - = negative; i.p. = intraperitoneal injection

         In  Drosophila melanogaster, no statistically significant
    sex-linked recessive lethals were obtained after exposure to phenol
    via a variety of techniques (Sturtevant, 1952; Wild  et al., 1980;
    Gocke  et al., 1981; Woodruff  et al., 1985). However, when an
    unusual technique was used, i.e. exposing isolated gonads  in vitro
    and implanting them in host larvae, several types of mutations were
    induced (Hadorn & Niggli, 1946).

         When rainbow trout ( Salmo gairdneri) were exposed to phenol
    for 72 h at concentrations of 0.3 and 0.6 µl phenol/litre water, the
    percentage of chromosomal aberrations in gill and kidney tissue was
    significantly increased, at both concentrations, in a dose-related
    way. Of these aberrations, 30% were structural, 45% consisted of
    aneuploidy, and 25% were non-specified metaphases (Al-Sabti, 1985).  Mammalian in vitro systems

         Data on  in vitro genotoxicity in mammalian cells are given in
    Table 8.

         In a Chinese hamster V79 lung cell/HPRT mutation test, phenol
    gave a positive result with metabolic activation. The highest dose
    decreased survival by approximately 50% (Pashin & Bakhitova, 1982).
    In a mouse lymphoma L5178Y cell/TK mutation test, there were
    statistically significant and dose-related increases in mutation
    frequency in the presence and absence of metabolic activation
    (Wangenheim & Bolcsfoldi, 1988). However, in another laboratory this
    test yielded non-conclusive results (McGregor  et al., 1988).

         As part of the US NTP testing program, phenol was evaluated for
    induction of chromosomal aberrations and sister chromatid exchange
    (SCE) in Chinese hamster ovary (CHO) cells (Ivett  et al., 1989).
    At a delayed harvest time (22.5 h), there were significantly
    increased incidences of aberrations in cultures that included a
    metabolic activation system from induced rat liver. Although a
    dose-response effect was seen, the frequency of aberrations in the
    absence of activation was low and the authors reported a negative
    result. Regarding SCE induction, positive results were obtained,
    both with and without activation. In additional studies, phenol
    induced SCE in human lymphocytes  in vitro, both in the presence
    and in the absence of metabolic activation (Morimoto & Wolff, 1980;
    Morimoto  et al., 1983; Erexson  et al., 1985). Negative results
    (SCE) have also been reported (Jansson  et al., 1986).

         Phenol gave negative results in three studies in Chinese
    hamster V79 cell metabolic cooperation assays (Chen  et al., 1984;
    Malcolm  et al., 1985; Bohrman  et al., 1988).  Mammalian in vivo system: somatic cells

         In a bone marrow micronucleus test, groups of four Swiss CD-1
    mice (sex not specified) were orally administered 265 mg phenol/kg
    body weight and were sacrificed at 0, 18, 24, 42 and 48 h. Bone
    marrow depression (decreased polychromatic erythrocytes/normocytes
    (PCE/NCE) ratio) persisted at least up to 48 h after dosing. A
    slight, but statistically significant, increase in the number of
    micronuclei was seen at 24 h (3 micronuclei/1000 cells versus 1.5
    micronuclei/1000 cells; 3000 cells scored per mouse) (Ciranni  et
     al., 1988b).

         In a further study to asses the transplacental clastogenicity
    of phenol, groups of 4 pregnant Swiss CD-1 mice received 265 mg
    phenol/kg/body weight by oral gavage on day 13 of gestation. After
    15, 18, 24, 30, 36 or 40 h, animals were sacrificed and adult bone
    marrow cells and fetal liver cells were scored for micronuclei.
    Slight, but statistically significant, increases in the frequency of
    micronucleated PCE in adult bone marrow were observed at 15, 18 and
    24 h (3.8, 4.0 and 5.0 micronuclei/1000 cells, respectively,
    compared with 2/1000 for negative controls). A statistically
    significant reduction in the PCE/NCE ratio was seen at 18 and 36 h.
    Phenol had no effect on the frequency of micronuclei in fetal liver
    (Ciranni  et al., 1988a).

         Bone marrow liver cells were also evaluated for the formation
    of micronuclei, 30 h after oral administration of 0 or 250 mg
    phenol/kg body weight to groups of five males Swiss CD-1 mice
    (Gad-El Karim  et al., 1986). Uptake was indicated by convulsive
    seizures in all mice receiving phenol (1000 PCEs scored per mouse).

         Phenol (265 mg/kg body weight), administered to Swiss CD-1 mice
    by a single intraperitoneal injection, was reported to increase the
    frequency of micronuclei in bone marrow PCEs 18 h post-treatment (7
    micronuclei/1000 cells). The increased frequency decreased at 24 h
    and was no longer statistically significant at 42 h. A decreased
    PCE/NCE ratio persisted in tests up to 48 h post-treatment (Ciranni
     et al., 1988b).

         Barale  et al. (1990) reported a negative result in a bone
    marrow micronucleus test in Swiss CD-1 mice 18 h after treatment
    with phenol. There was no effect on the PCE/NCE ratio.

         Gocke  et al. (1981) briefly reported a negative result in a
    bone marrow micronucleus test, in which NMRI mice were sampled at 30
    h, following i.p. injection of 47-188 mg phenol/kg. No information
    on toxicity was given.

         The results of these and other studies are summarized in Table
    9.  Mammalian in vivo systems: germ cells

         Skare & Schrotel (1984) obtained negative results in studies of
    DNA strand breakage in rat testis. In one experiment, rats received
    by intraperitoneal injection 0, 7.9, 26 or 79 mg phenol/kg body
    weight and were sacrificed at 2.6 or 24 h post-treatment. Similar
    results were obtained with further groups of rats that received 4,
    13.2 and 39.5 mg phenol/kg body weight daily for 5 days before

         In an unconventional study involving dosing (0, 6.4, 64 and 640
    mg phenol/kg body weight) of five successive generations of male and
    female mice, large numbers of structural and numerical chromosomal
    aberrations were reported in spermatocytes and spermatozoa, with
    dose- and generation-related increases. The study was carried out
    with 138 male mice from an inbred stock after skin testing
    (Bulsiewicz, 1977).

    7.7  Carcinogenicity

         The evidence for the carcinogenicity of phenol in experimental
    animals, based on the studies summarized below, was recently
    considered by the IARC (1989) to be inadequate. Phenol was
    classified by US EPA in Group D (data inadequate for evaluating the
    carcinogenic potential) (Bruce  et al., 1987).

    7.7.1  Oral exposure

         In an NCI (1980) study, groups of 50 male and 50 female
    B6C3F1 mice were given drinking-water containing 0, 2500 or 5000
    mg phenol/litre for 103 weeks. As matched controls, groups of 50
    male and 50 female mice received tap water. There was a dose-related
    decrease in water consumption and mean body weight gain in all
    groups of mice. In mice receiving 5000 mg phenol/litre, an increase
    in the number of uterine endometrial stromal polyps (5/48 = 10%) was
    observed (in matched controls the incidence was 1/50 = 2%). There
    was no evidence of an increased incidence of malignant tumours. The
    other observed neoplasms were of the usual number and type found in
    mice of this strain and age (NCI, 1980).

         Groups of 50 male and 50 female Fischer-344 rats received 0,
    2500 or 5000 mg phenol/litre drinking-water for 103 weeks, while the
    matched control group received tap water. Male and female rats given
    5000 mg/litre showed a decrease in mean body weight from week 20
    onwards. There were statistically significant increased incidences
    of phaeochromocytomas, leukaemias, lymphomas and C-cell thyroid
    carcinomas in males of the low-dose group (NCI, 1980). NTP
    considered this study negative for carcinogenicity due to the lack
    of a dose-response for the neoplasms and the lack of response in

    7.7.2  Dermal exposure

         Three studies examined the potential carcinogenicity of phenol
    following dermal application (Rusch  et al., 1955, Boutwell  et
     al., 1956; Bernard & Salt, 1982). However, none is considered
    adequate for the evaluation of carcinogenicity due to the short
    duration of exposure and/or use of inappropriate vehicles.

    7.7.3  Inhalation exposure

         No studies have been reported for this route of exposure.

    7.7.4  Two-stage carcinogenicity studies

         A dose of 3 mg phenol in acetone was applied to ICR/Ha Swiss
    mice 3 times per week for 52 weeks after initiation with 150 µg
    DMBA. Papilloma development was enhanced, compared with that of mice
    exposed to DMBA alone (Van Duuren  et al., 1968; Van Duuren &
    Goldschmidt, 1976). These observations were in agreement with those
    from earlier reports on the promotional activity of phenol (Boutwell
     et al., 1955, 1956; Salamon & Glendenning, 1957; Boutwell & Bosch,
    1959; Wynder & Hoffmann, 1961).

         A dose of 3 mg phenol in acetone applied 3 times weekly for 460
    days to female ICR/Ha Swiss mice after initiation with 5 µg
    benzo[a]pyrene had a slight promoting activity. Simultaneous
    application of both agents showed a partial reduction in carcinomas
    compared with mice treated with benzo[ a]pyrene alone (Van Duuren
     et al., 1971, 1973; Van Duuren & Goldschmidt, 1976).

    7.8  Special studies

    7.8.1  Neurotoxicity

         Tremors, convulsions, coma and death were reported after
    intraperitoneal and subcutaneous doses of phenol (Deichmann &
    Witherup, 1944; Ernst  et al., 1961; Windus-Podehl  et al., 1983).
    The tremors were enhanced by prior monoamine depletion following
    reserpine treatment (Suzuki & Kisara, 1985).

         Upon histological examination of rats in which convulsions had
    been induced by subcutaneous phenol injection (200 mg/kg body weight
    given once a week for two weeks), two out of six animals showed
    spinal cord and spinal root degeneration (Veronesi  et al., 1986).

         Phenol, given either intravenously or intra-arterially (250
    µg), facilitated neuromuscular transmission and antagonized
    neuromuscular blockade by D-tubocurarine in cats. The effect was
    determined to be pre-synaptic in origin (Blaber & Gallagher, 1971).

         Phenol caused diminution of the compound action potential in
    preparations of the saphenous nerve after acute and chronic
    perfusion (Schaumburg  et al., 1970).

         Groups of five male CD-1 mice were supplied with drinking-water
    containing 0, 4.7, 19.5 or 95.2 mg phenol/litre for 4 weeks, at the
    end of which the concentrations of various neurotransmitters and
    their metabolites were measured in different parts of the brain. The
    largest effects were seen in levels of noradrenaline in the
    hypothalamus (significant decreases of 29 and 40% in the mid- and
    high-dose groups) and of dopamine in the corpus striatum
    (significant decreases of 21, 26 and 35% in the low-, mid- and
    high-dose groups). There were dose-related, but not always
    statistically significant, decreases in all of the neurochemicals
    measured in the hypothalamus: noradrenaline, dopamine,
    vanillylmandelic acid (VMA), 3,4-dihydroxy-phenylacetic acid
    (dopac), homovanillic acid (HVA), serotonin (5-HT) and
    5-hydroxyindoleacetic acid (5-HIAA). There were significant
    decreases in VMA in the midbrain, corpus striatum and cortex, 5-HT
    in the midbrain, corpus striatum and medulla oblongata, and dopac in
    the cerebellum in the high-dose group only. There were also
    significant decreases in 5-HT and 5-HIAA in the hypothalamus of the
    mid- and high-dose groups (Hsieh  et al., 1992).

         Continuous exposure of rats to 0.012, 0.12 and 5.3 mg
    phenol/m3 for 61 days caused a shorter extensor muscle chronaxy
    and an increase in whole-blood cholinesterase activities in rats at
    concentrations above 0.012 mg phenol/m3 (Mukhitov, 1964).

    7.8.2  Myelotoxicity

         Because phenol is an important metabolite of benzene, which is
    known to exert a toxic effect on bone marrow (including leukaemia)
    after metabolic activation, many studies have been performed to
    investigate the possible myelotoxic action of phenol.

         In an  in vitro assay for toxicity to primary murine
    haematopoietic cell cultures, phenol showed slight and variable
    activity at a concentration of 0.4 mM, but there was marked toxicity
    at 2 mM. In comparison, the phenol metabolites catechol and
    hydroquinone exhibited marked toxicity at 0.04 mM (Seidel  et al.,

         Subcutaneous treatment with phenol (245 mg/kg body weight)
    significantly inhibited erythropoiesis in mice 48 h after treatment,
    as indicated by a 59Fe uptake assay (Bolcsak & Nerland, 1983).

         Intraperitoneal injection of 0-150 mg phenol/kg body weight to
    male B6C3F1 mice, twice daily for 12 days, did not result in a
    suppression of bone marrow cellularity. However, simultaneous
    treatment of mice with 75 mg phenol/kg body weight and 25-75 mg

    hydroquinone/kg body weight (another benzene metabolite), produced a
    dose-related decrease in bone marrow cellularity, which was much
    more pronounced than after treatment with hydroquinone only. The
    observed effect closely resembled the myelotoxic effect of benzene
    (Eastmond  et al., 1987b).  Subsequent  in vitro studies by these
    and other investigators confirmed that phenol (0.01-1 mM) stimulates
    further bioactivation of hydroquinone to myelotoxic compounds in
    bone-marrow cells (Eastmond  et al., 1987b; Subrahmanyam  et al.,

         No haematopoietic toxicity was found in rats after daily
    subcutaneous injections of 250-750 mg phenol/kg body weight for 1
    week. Of the rats receiving 750 mg phenol/kg body weight, 50% died
    (Mitchell, 1972).

         Six consecutive subcutaneous injections of 50 mg phenol/kg body
    weight to mice resulted in a slightly but significantly reduced
    number of granulopoietic stem cells and bone marrow cellularity in
    the tibia (Tunek  et al., 1981).

    7.8.3  Immunotoxicology

         One immunological study has been reported. Female CD1 mice were
    exposed to 19 mg phenol/m3 (5 ppm), either as a single 3-h
    exposure or as five daily 3-h exposures. Neither the susceptibility
    of the animals to experimentally induced streptococcus aerosol
    infection nor their pulmonary bactericidal activity was
    significantly affected (Aranyi  et al., 1986).

         Groups of five male CD-1 mice were supplied with drinking-water
    containing 0, 4.7, 19.5 or 95.2 mg phenol/litre for 4 weeks, at the
    end of which various haematological and immunological parameters
    were measured. The erythrocyte count was statistically significantly
    decreased, compared with control values, in all treated groups in a
    dose-related manner, but total and differential leucocyte counts
    were unaffected. Total spleen cellularity was decreased in a
    non-significant dose-related manner. The highest dose suppressed the
    stimulation of cultured splenic lymphocytes by the B-cell mitogen
    lipopolysaccharide, the T-cell mitogen phytohaemagglutinin, and the
    T- and B-cell mitogen pokeweed, but not by concanavatin. The mid and
    high doses suppressed the animals' antibody production in response
    to a T-cell-dependent antigen, i.e. sheep erythrocytes (Hsieh  et
     al., 1992).

    7.8.4  Biochemical effects

         In a study on the biochemistry of intestinal mucosa, mice were
    provided with 0,5, 50 or 500 mg phenol/litre drinking-water
    (calculated by the authors to be 1, 10 and 100 mg phenol/kg body
    weight) for 5 days or 5 months at 1-day intervals. An increase in
    glucose-6-phosphatase, succinate dehydrogenase and cytochrome

    oxidase activities in the intestinal mucosa was observed in mice
    receiving > 0.02 mg phenol/kg body weight for 5 days. A decrease
    in these activities was seen at 2 mg phenol/kg body weight. After 5
    months administration of 0.02 and 0.2 mg phenol/kg body weight, the
    enzyme activity had returned to normal, but the highest dose group
    showed a decline (or even a lack) of activity in the cells of the
    intestinal mucosa (Olowska  et al., 1980).

         In another study of biochemical effects, mice were provided for
    5 days (killed 24 h after the last application) and 35 days (killed
    30 days after the last application) with aqueous solutions of 0.08,
    0.8 or 8 mg phenol/litre. The authors of the study calculated the
    doses to be approximately 0.016, 0.16 and 1.6 mg phenol/kg body
    weight per day, respectively. Only the lowest dose of 0.08 mg
    phenol/litre evoked considerable changes in the localization of
    glucose-6-phosphatase, 5 days after treatment. Changes in alkaline
    phosphatase localization in the kidney were seen at 0.8 and 8 mg
    phenol/litre. Full recovery occurred after 30 days (Laszczynska  et
     al., 1983).

         Inhalation exposure of 50 male white rats to 0.4 mg
    phenol/m3, 24 h/day, 7 days/week, for 3 months, resulted in some
    inhibition of oxidative phosphorylation in the lungs, liver and
    kidneys. An increase in the rate of glycolysis was also observed in
    the lungs and kidneys (Skvortsova & Vysochina, 1976).


    8.1  General population exposure

    8.1.1  Controlled studies

         In the Kligman maximization test, phenol did not cause
    sensitization in 24 human volunteers (Kligman, 1966).

         It was reported by Rea  et al. (1987) that, in a group of 134
    "chemically sensitive" patients where several volatile organic
    chemicals were detected in the blood, 107 (80%) reacted adversely
    after a challenge exposure to phenol alone (0.008 mg/m3). The
    criteria used to identify "sensitive patients" and "adverse
    reactions" were not specified. The toxicological significance of
    this finding is not known.

         Mukhitov (1964) reported that six 5-min inhalation exposures to
    phenol at 0.015 mg/m3 produced an increased sensitivity to light
    in each of 3 dark-adapted subjects.

    8.1.2  Case reports

         Various reports have appeared on the adverse effects of phenol
    in individuals or groups of humans after intentional (e.g.,
    therapeutic) as well as accidental short-term exposure to phenol.  Dermal exposure

         The use of phenol as a disinfectant and antiseptic was
    introduced by Lister (1867). However, its use has been restricted by
    intoxications caused by these applications (Table 10).

         Local effects after dermal phenol exposure consisted of
    erythema or painless blanching (Dreisbach, 1983), and, in more
    severe cases, corrosion (Schmidt & Maibach, 1981) and necrosis. The
    use of 5-10% phenol dressings for antiseptic purposes, for example,
    has led to many cases of necrosis of the skin and underlying
    tissues. When fingers and toes have been involved, amputation has
    sometimes been necessary. Due to their high toxicity, these
    dressings are no longer used (Cronin & Brauer, 1949; Deichmann,
    1949; De Groote & Lambotte, 1960; Abraham, 1972).

         Phenol chemical peel is a technique which has been used in
    superficial surgery of the skin for the last 30 years (Ersek, 1991).
    The phenolic mixture used classically is 3 ml of 50% phenol, 2 ml of
    water, 8 drops of soap and 8 drops of croton oil. This is applied to
    the skin to reduce pigmentation. Topical use of phenol as a chemical
    face-peel has been reported as being associated with cardiac
    dysrhythmias in "up to 30% of adults" (Morrison  et al., 1991), but
    only a single case report has been published (Warner & Harper,
    1985). This report concerned a 10-year-old boy who had a solution,
    consisting of 40% phenol and 0.8% croton oil in hexachlorophene soap
    and water, applied to a large nevus covering 1.9% of his body
    surface whilst under anaesthesia (60% nitrous oxide and 3%
    halothane) and receiving a total of 200 ml of lactated Ringer's
    solution intravenously. After 55 min of treatment, multifocal and
    coupled premature ventricular complexes were detected by ECG, but
    blood pressure remained stable and plasma sodium and potassium
    concentrations were normal. An intravenous infusion of 250 mg
    bretylium sulfate suppressed the dysrhythmia and the boy had an
    uneventful recovery.

         Systemic intoxication can occur very rapidly after absorption
    of phenol through the skin (Table 10). Most significantly,
    cardiovascular shock (sometimes resulting in death) and severe
    metabolic acidosis occur. Truppman & Ellenby (1979) observed cardiac
    arrhythmias (supraventricular as well as ventricular) in 10 out of
    42 patients within 10 min after the application of approximately 5%
    phenol on half of the face for cosmetic treatment. Hyperventilation,
    kidney damage and methaemoglobinaemia have also been observed in
    several cases of exposure to phenol.

    Table 10.  Human dermal toxicity of phenol
    Concentration   Medium        Contact duration   Circumstances                 Most severe response        References

    100             crystals      30 min             in glove                      grangrene                   Abraham (1972)

    80-100          water         20 min             spill on hip, thigh, death    Turtle & Dolan
                                                     scrotum                       (1922)

    80-100          water         2-4 days           closed dressings on           11 persons exposed:         Lister (1867)
                                                     open wounds                   1 death, 8 gas gangrene,
                                                                                   11 tissue necrosis

    78              water         2-5 min            4-5 litres spilt on           coma                        Duverneuil &
                                                     upper half of body                                        Ravier (1962)

    43.5            waste water   1 min              spill on lower half of body   shock                       Evans (1952)

    5               ointment      7 days             closed dressing on cut        gangrene                    Schussler &
                                                                                                               Stern (1911)

    2               water         2.5 days           moist dressing over burns     death                       Cronin & Brauer
                                                     on 30% of body surface                                    (1949)

    2               water         11 h               closed bandage on             death                       Hinkel & Kintzel
                                                     infant umbilicus                                          (1968)

         Foxall  et al. (1991) reported a case of acute renal failure
    following an industrial accident in which a man was partially
    submerged for a few seconds in a solution of 20% phenol in
    dichloromethane. He immediately showered, but was subsequently found
    in a state of collapse. His extremities were cold and he had 50%
    body burns. He developed nausea and vomiting after taking fluids.
    Anuria ensued, with a rise in plasma creatinine, but treatment with
    intravenous furosemide and haemodyalisis (daily for seven days, then
    with decreasing intervals for a further 18 days), allowed adequate
    urinary volumes to be produced. Respiratory distress required
    intensive care treatment. Marginal polyuria persisted one year after
    the accident.  Oral exposure

         Cases of oral intoxication have occurred as a result of
    accidental and intentional ingestion. Local and systemic effects
    have been described in the literature, symptoms being similar to
    those following dermal exposure. Case reports have been published
    (Model, 1889; Stajduhar-Caric, 1968; Haddad  et al., 1979).

         Death occurred within 10 min of ingestion of 4.8 g phenol
    (Andersen, 1869). However, ingestion of 56.7 g of a phenol-saline
    mixture was reported to have occurred without complaints (Leider &
    Moser, 1961), and an individual survived the ingestion of 57 g
    phenol (88%) after intensive treatment. Symptoms in the latter study
    included severe gastrointestinal irritation, as well as the expected
    cardiovascular and respiratory effects (Bennett  et al., 1950).

         A severe accidental phenol spill in Wisconsin in 1974
    contaminated ground water which was being used as drinking-water.
    Approximately one month later, several people living near the spill
    complained of health effects. Six months after the spill, medical
    histories were taken from 100 people who had consumed
    phenol-contaminated water (the authors estimated the daily exposure
    to be 10-240 mg phenol/person). In retrospect, a statistically
    significant increase was found in diarrhoea, mouth sores, dark urine
    and burning of the mouth, which had persisted for an average of 2
    weeks. No significant abnormalities were found 6 months after
    initial exposure upon physical examination or laboratory analysis.
    Urinary phenol levels were not elevated (Delfino & Dube, 1976; Baker
     et al., 1978).

         A river in North Wales, United Kingdom, used for the
    preparation of drinking-water, was accidentally contaminated with
    phenol (Jarvis  et al., 1985). When the water was chlorinated,
    various chlorophenols appeared to have been formed. A retrospective
    postal survey of 344 households that received the contaminated tap
    water and 250 control households was carried out. Significantly more
    gastrointestinal illnesses, as well as other symptoms, were claimed
    in the contaminated areas than in the unexposed areas. Phenol

    concentrations in drinking-water were conservatively estimated to
    have been 4.7-10.3 µg/litre for some days (Jarvis  et al., 1985).  Inhalation exposure

         Very few cases of adverse effects after short-term phenol
    vapour exposure have been reported.

         Hospital outbreaks of severe idiopathic neonatal unconjugated
    hyperbilirubinaemia have been associated with the phenol-containing
    disinfectant used for cleaning the nursery equipment, floors and
    walls. When the disinfectant was no longer used, the epidemic
    subsided (Daum  et al., 1976; Wysowski  et al., 1978; Doan  et
     al., 1979).

         Studies of occupational inhalation exposure are described in
    section 8.2.  Exposure by injection

         Phenol has been used as a neuron blocking agent in patients
    suffering from spasm following, for example, spinal cord damage or
    cerebrovascular stroke (Wood, 1978, review; Nathan, 1959; Cooper  et
     al., 1965; Khalili & Betts, 1967; Gibson, 1987). It has also been
    used to relieve chronic pain (Wood, 1978; Benzon, 1979; Smith,
    1984). Treatment involved administering the phenol by intravenous
    injection or perfusion, or by direct injection into the spinal cord.
    Reported side-effects of phenol therapy were convulsions, transient
    paraesthesia, leg weakness, urinary and fecal incontinence, one case
    of a severe arterial block in the upper arm requiring amputation,
    and one case of acute bronchospasm (Wood, 1978, review; Benzon,
    1979; Gibson, 1987; Atkinson & Skupak, 1989). In addition, there
    have been reports of phenol-induced cardiac dysrhythmia in adults
    (Forrest & Ramage, 1987) and in children, in whom an incidence of
    19% was reported (Morrison  et al., 1991).

    8.2  Occupational exposure

         Poisoning due to chronic inhalation of phenol was known 100
    years ago, primarily as a disorder in physicians and their helpers,
    under the term "carbol marasmus" (Lister, 1867). A classical case of
    phenol marasmus was described in a worker employed for 13´ years in
    a laboratory boiling phenol solutions. Symptoms were anorexia,
    weight loss, headache, vertigo, salivation and dark urine (Merliss,

         A few studies are available concerning occupational exposure of
    workers in bakelite factories. Workers were exposed to phenol, and
    simultaneous exposure to formaldehyde occurred. Elevated phenol
    urine levels, unspecified complaints, and chronic airway obstruction
    were observed (Schoenberg & Mitchell, 1975; Knapik  et al., 1980).

         Twenty-nine cases of poisonings among workers, who, during a
    3-year period, quenched coke with a waste-water solution containing
    0.3-0.8 g phenol/litre, were attributed to phenol intoxication.
    Phenol vapour concentrations in the air ranged from 0.5 to 12.2
    mg/m3. The number of workers and the symptoms of intoxication were
    not specified. The author did not consider the potential of dermal
    absorption (Petrov, 1960).

         A case-control study was carried out on 57 cases among 3805
    workers from the Finnish wood industry (particle board, plywood,
    sawmill or formaldehyde glue) suffering from respiratory cancer. The
    inhalatory exposure level to phenol and frequency of multiple
    exposure to pesticides were found to be significantly higher for
    cancer cases, but the exposure to wood dust was not significantly
    different between cases and controls (Kauppinen  et al., 1986). The
    number of cases in this study was small, and confounding exposures
    were inadequately controlled.

         In a case-control study of 6678 rubber workers, employed in
    areas where phenol was used, exposure to phenol was not associated
    with increased risks of cancer of the respiratory tract, stomach or
    prostate or of lymphosarcoma or lymphatic leukaemia (Wilcosky  et
     al., 1984).

         A mortality study was conducted among 14 861 white male workers
    engaged in the production or use of phenol and formaldehyde in five
    companies within the USA. The follow-up comprised more than 360 000
    man-years. Mortality rates from all causes combined were similar to
    those in the general population of the USA. Excesses of cancer of
    the oesophagus, cancer of the kidney and Hodgkin's disease were
    observed among the workers exposed to phenol, but these did not show
    any exposure-response relationship and were not statistically
    significant. Reduced mortality ratios were observed for cancer of
    the buccal cavity and pharynx, cancer of the stomach, cancer of the
    brain, arteriosclerotic heart disease, emphysema, disease of the
    digestive system and cirrhosis of the liver, although these
    reductions were not statistically significant. For arteriosclerotic
    heart disease, emphysema and cirrhosis of the liver, there were
    inverse relationships between mortality rates and duration of phenol
    exposure and cumulative phenol exposure levels (Dosemeci  et al.,

         A cardiovascular disease (CVD) mortality study was conducted
    among 1282 white male production workers in a large rubber- and
    tyre-manufacturing plant. Exposure estimates for 25 solvents were
    available (concentrations were not measured). The CVD mortality
    during 15-year follow-up period was analyzed in exposed and not
    exposed workers. The known association between CS2 exposures and
    ischemic heart diseases (IHD) was confirmed, and two other solvents,
    ethanol and phenol, were also found to be predictors of IHD. Phenol
    showed the strongest association with CVD mortality. However, some

    confounders (cigarette smoking, hypertension and high serum
    cholesterol) were not controlled and unrecognized chemical
    atherogens could also, according to the authors, influence the
    results (Wilcosky & Tyroler, 1983).

    8.3  Organoleptic data

         The odour threshold for phenol has been reported to range from
    0.021 to 20 mg/m3 (Van Gemert & Nettenbreijer, 1977; Van Gemert,

         The geometric mean of 16 air odour thresholds and 6 water odour
    thresholds for phenol was reported by Amoore & Hautala (1983) to be
    0.16 mg/m3 (0.040 ppm, with a standard error of 0.026 ppm). In
    this calculation, the original literature was reviewed and values
    which diverged more than 100-fold from the nearest of two or more
    other thresholds were eliminated. Both detection and recognition
    values were included. The water detection threshold for phenol,
    based upon multiplying the calculated air odour threshold by the
    water-air distribution ratio, was reported by the same authors to be
    7.9 mg/litre.

         A taste threshold value of 0.3 mg/litre in water has been
    reported (US EPA, 1992).


         The toxicity of phenol has been studied in microorganisms
    (e.g., bacteria, fungi, algae and protozoa) and numerous aquatic
    invertebrates and vertebrates (Buikema  et al., 1979). Because of
    this vast amount of data, a selection has been made, based on the
    reliability of the data and the relevance of the test organisms.
    Details of acute and long-term aquatic toxicity studies, considered
    to be adequately performed and reported, are included in Tables 11
    and 12. Less adequate studies are reported in the text only.

    9.1  Microorganisms

         Reliable phenol toxicity data for microorganisms are given in
    Table 11.

         In microorganisms, growth inhibition is usually observed after
    phenol exposure. In studies on single bacterial species, the EC50
    values (EC50 = calculated concentration affecting 50% of test
    population) found for growth inhibition varied from 244 mg
    phenol/litre in a newly developed, 6-h test with  Pseudomonas putida
    (Slabbert, 1986) to 1600 mg phenol/litre after 18 h of exposure in a
    more conventional test with  Aeromonas hydrophila (Dutka & Kwann,
    1981). Bringmann & Kühn (1977) reported a toxicity threshold of 64
    mg/litre after 16 h. EC50 values for reduced photoluminescence in
     Photobacterium phosphoreum of 28-34 mg phenol/litre (Dutka  et
     al., 1983) and 40 mg phenol/litre (Curtis  et al., 1982) have
    been reported. In activated sludge, the EC50 for a reduced oxygen
    uptake was reported to be 520-1500 mg phenol/litre, whereas a lower
    value was found for substrate consumption inhibition (104 mg
    phenol/litre) (Miksch & Schürmann, 1988; Volskay & Grady, 1988). The
    lowest reported concentration affecting activated sludge was 10 mg
    phenol/litre; 1 mg phenol/litre had no effect (Baird  et al.,

         Reported toxicity thresholds for protozoa were of the same
    order of magnitude as for bacteria: 33-144 mg phenol/litre
    (Bringmann & Kühn, 1959, 1980; Dive & LeClerq, 1977; Bringmann  et
     al., 1980). For algae, values were somewhat lower, but were
    observed after a longer exposure period: 6 mg phenol/litre for
    cyanobacteria (blue-green algae) and 8 mg phenol/litre for green
    algae, after 7-8 days of exposure (Bringmann & Kühn, 1978, 1980).
    The IC50 values (concentration causing 50% growth inhibition)
    reported for various fungi by Kwasniewska & Kaiser (1983) were of
    the same order of magnitude as the above EC50 values for bacterial
    growth inhibition: 460-1000 mg phenol/litre. These values are also
    within the range of concentrations observed by Babich & Stotzky
    (1985) to cause initial or complete growth inhibition in various
    fungi (100-1000 mg phenol/litre and 750->1000 mg phenol/litre,

    Table 11.  Acute aquatic toxicity of phenol

    Organism                 Temperature  pH           Dissolved   Hardness     Methoda  Test         Parameterb  Concentration   Reference
                             (°C)                      oxygen      (mg CaCO3/            duration                 (mg/litre)
                                                       (mg/litre)  litre)

    Freshwater Organisms

    Photobacterium           15           6.5-6.7                               S        5, 10,       EC50c       28, 32, 34      Dutka et al.
    phosphoreum                                                                          15 min                                   (1983)

    Pseudomonas putida       25           7.0                      80.1         S        16 h         TTc         64              Bringmann &
                                                                                                                                  Kuhn (1977)
                             27           7.2                                   S        6 h          EC50        244             Slabbert

    Microcystis aeruginosa   27           7.0                      72.3         S        8 days       TT          6               Bringmann &
                                                                                                                                  Kuhn (1978)

    Green algae
    Scenedesmus              27           7.0                      72.3         S        7 days       TT          8               Bringmann &
    quadricauda                                                                                                                   Kuhn (1980)

    Chilomonas               20           6.9                                   S        48 h         TT          65              Bringmann et
    paramaecium                                                                                                                   al. (1980)

    Colpidium campylum       20                                                 S        43 h         TTd         100             Dive & LeClerq

    Entosiphon sulcatum      25           6.9                      80.1         S        72 h         TT          33              Bringmann &
                                                                                                                                  Kuhn (1980)

    Microregma heterostoma   27           7.5-7.8      213.6                    S        28 h         TT          30e             Bringmann &
                                                                                                                                  Kuhn (1959)

    Table 11 (contd).

    Organism                 Temperature  pH           Dissolved   Hardness     Methoda  Test         Parameterb  Concentration   Reference
                             (°C)                      oxygen      (mg CaCO3/            duration                 (mg/litre)
                                                       (mg/litre)  litre)

    Uronema parduczi         25           7.3                                   S        20 h         TT          144             Bringmann &
                                                                                                                                  Kuhn (1980)
    Asellus aquaticus        11 ± 1       7.5-8.1                  99.5 ± 7.7   S        24, 48,      LC50        230, 200,       Green et al.
                                                                                         96 h                     180f            (1985)

    Cypris subglobosa        20.4         7.9          8.4         204          S        12, 24, 48,  LC50        173, 167,       Rao et al.
                                                                                         72, 96 h                 137, 122, 72    (1983)

    Daphnia magna            19.8-20.9    7.7-8.3                  157 ± 4      S        48 h         LC50        13              Gersich et
                                                                                                                                  al. (1986)
                             19 ± 1       8.2 ± 0.3                199.4        S        48 h         LC50        100f            Hermens (1984)
                             19 ± 1       8.2 ± 0.3                199.4        S        48 h         EC50g       9f              Hermens (1984)
                             17.2 ± 0.5   7.4 ± 0.2    8.7 ± 1.1   44.7         S        24 h         LC50h       13              Holcombe et
                                                                                                                                  al. (1987)
                                                                                S        48 h         EC50g       7               Keen & Baillod
                             22 ± 1       6.8-7.8      7.6 ± 0.2   146 ± 15     S        48 h         LC50        8               Lewis (1983)

    Gammarus pulex           11 ± 1       7.5-8.1      99.5 ± 7.7               S        24, 48,      LC50        106, 85,        Green et al.
                                                                                         96 h                     69f             (1985)
                             7 ± 1        8.3          10.9        250          R        24, 48,      LC50        100, 89,        Stephenson
                                                                                         72, 96 h                 67, 51          (1983)

    Ceriodaphnia dubia       25 ± 1       8.18 ± 0.04              57.1 ± 4.1   S        48 h         LC50        3.1             Oris et al.

    Indoplanorbis                                                               S        12, 24, 48,  LC50        265, 215, 200,  Agrawal (1987)
    exustus                                                                              72, 96 h                 156, 126

    Table 11 (contd).

    Organism                 Temperature  pH           Dissolved   Hardness     Methoda  Test         Parameterb  Concentration   Reference
                             (°C)                      oxygen      (mg CaCO3/            duration                 (mg/litre)
                                                       (mg/litre)  litre)

    Lymnaea acuminata        20 ± 2       7.9 ± 0.2    5.5 ± 1.5   190-223      R        12, 24, 48,  LC50        270, 219, 205,  Gupta & Rao
                                                                                         72, 96 h                 158, 129        (1982)

    Limnodrilus              11 ± 1       7.5-8.1                  99.5 ± 7.7   S        24, 48,      LC50        960, 870,       Green et al.
    hoffmeisteri                                                                         96 h                     780f            (1985)

    Polycelis felina         18           7-8.5        -i**          300-500      S        96 h         LC50        64f             Erben et al.

    Polycelis tenuis         11 ± 1       7.5-8.1                  99.5 ± 7.7   S        24, 48,      LC50        230, 200,       Green et al.
                                                                                         96 h                     88f             (1985)

    Brachydanio rerio        25 ± 0.5     8.0-8.3      -i          350-375      CF       48, 96 h     LC50        31, 29f         Fogels &
                                                                                                                                  Sprague (1977)
                             24 ± 1                    > 6         64           R        6, 12, 24,   LC50        35, 31, 28,     Razani et al.
                                                                                (12 h)   48, 72, 96 h             26, 25, 25f     (1986a)

    Campostoma anomalum      23                        -i                       R        48 h         LC50        18f             Chagnon &
                                                                                (24 h)                                            Hlohowskyj

    Catostomus               17.2 ± 0.5   7.4 ± 0.2    8.7 ± 1.1   44.7         S        96 h         LC50h       11              Holcombe et
    commersoni                                                                                                                    al. (1987)

    Jordanella floridae      25 ± 0.5     8.0-8.3      -i          350-375      CF       48, 96 h     LC50        36, 36f         Fogels &
                                                                                                                                  Sprague (1977)

    Lebistes reticulatus     28-31.8      7.8-8.2      5.7-7.2     218-239      R        12, 24, 48,  LC50        103, 83, 64,    Gupta et al.
                                                                                (24 h)   72, 96 h                 50, 48          (1982a)

    Table 11 (contd).

    Organism                 Temperature  pH           Dissolved   Hardness     Methoda  Test         Parameterb  Concentration   Reference
                             (°C)                      oxygen      (mg CaCO3/            duration                 (mg/litre)
                                                       (mg/litre)  litre)

    Lepomis macrochirus      17.2 ± 0.5   7.4 ± 0.2    8.7 ± 1.1   44.7         S        96 h         LC50h       17              Holcombe et
                                                                                                                                  al. (1987)

    Leuciscus idus           20                                                 S        48 h         LC50        14, 25          Jünke &
    melanotus                                                                                                                     Lüdemann

    Notopterus notopterus    23-26.5      6.8-7.6      5.9-7.8     60-70        S        24, 48, 72,  LC50        14, 14, 13,     Verma et al.
                                                                                         96 h                     13              (1980)

    Pimephales promelas      17.2 ± 0.5   7.4 ± 0.2    8.7 ± 1.1   44.7         S        96 h         LC50h       25              Holcombe et
                                                                                                                                  al. (1987)
                             25 ± 2                    6.2-8.2     43-49        CF       96, 192 h    LC50        29, 23f         Phipps et al.

    Rasbora                  20           7.2                      250          S        24, 48 h     LC50        8, 7            Alabaster
    heteromorpha                                                                                                                  (1969)

    Rutilus rutilus          10.3 ± 0.3   7.8 ± 0.02               257-260      S        48 h         LC50        10f             Solbé et al.

    Salmo gairdneri          15 ± 0.5     8.0-8.3      -i          350-375      CF       48, 96 h     LC50        12 12f          Fogels &
                                                                                                                                  Sprague (1977)
                             17.2 ± 0.5   7.4 ± 0.2    8.7 ± 1.1   44.7         S        96 h         LC50i       11              Holcombe et
                                                                                                                                  al. (1987)

    Baetis rhodani           11 ± 1       7.5-8.1                  99.5 ± 7.7   S        24, 48,      LC50        19, 19, 16f     Green et al.
                                                                                         96 h                                     (1985)

    Chironomus riparius      11 ± 1       7.5-8.1                  99.5 ± 7.7   S        24, 48,      LC50        1050, 500,      Green et al.
                                                                                         96 h                     240f            (1985)

    Table 11 (contd).

    Organism                 Temperature  pH           Dissolved   Hardness     Methoda  Test         Parameterb  Concentration   Reference
                             (°C)                      oxygen      (mg CaCO3/            duration                 (mg/litre)
                                                       (mg/litre)  litre)

    Hydropsyche              11 ± 1       7.5-8.1                  99.5 ± 7.7   S        24, 48,      LC50        940, 720,       Green et al.
    angustipennis                                                                        96 h                     260f            (1985)

    Marine Organisms

    Artemia salina                                                              S        24, 48 h     LC50j       157, 56         Price et al.

    Canthocamptus            synthetic medium according to Cairns               S        48 h         LC50j       9               Rao & Nath

    Gammarus duebeni         5 ± 0.6      7.7 ± 0.1    8.4 ± 0.3   0.6%k        CF       96 h         LC50        183f            Oksama &
                             16 ± 0.6     7.7 ± 0.1    8.4 ± 0.3   0.6%k        CF       96 h         LC50        89f             (1979)

    Mesidotea entomon        5 ± 0.6      7.7 ± 0.1    8.4 ± 0.3   0.6%k        CF       96 h         LC50        176f            Oksama &
                             10 ± 0.6     7.7 ± 0.1    8.4 ± 0.3   0.6%k        CF       96 h         LC50        186f

    Panopeus herbstii        25                                    25 pptk      R        96 h         LC50        53              Key & Scott
                                                                                24 h                                              (1986)

    Crassostrea              24 ± 1                                seak         R        48 h (eggs)  LC50        58              Davis & Hidu
    virginica                                                                                                                     (1969)

    Mercenaria               24 ± 1                                seak         R        48 h (eggs)- LC50j       53-55           Davis & Hidu
    mercenaria                                                                           12 days                                  (1969)

    Table 11 (contd).

    Organism                 Temperature  pH           Dissolved   Hardness     Methoda  Test         Parameterb  Concentration   Reference
                             (°C)                      oxygen      (mg CaCO3/            duration                 (mg/litre)
                                                       (mg/litre)  litre)

    Ophryotrocha             21                                    seak         S        48 h         LC50        100-330         Parker (1984)

    Phoxinus phoxinus        5 ± 0.7      7.7 ± 0.1    8.4 ± 0.3   0.6%k        CF       96 h         LC50        10              Oksama &

    a  S = static test; CF = continuous flow test; R = renewal test (semi-static test)
    b  EC50 = median effect concentration = calculated concentration causing effect in 50% of population; LC50 = median lethal concentration
       TT = toxicity threshold, i.e. concentration affecting growth in > 3% of population
    c  effect: reduction in photoluminescence
    d  minimal concentration affecting growth
    e  river water
    f  concentration of test compound analysed during assay
    g  immobility
    h  simultaneous testing of 8 species
    i  no data; aerated
    j  reported was TLm, or median toxicity limit
    k  salinity; sea = sea water

    Table 12.  Long-term aquatic toxicity of phenol

    Organism      Temperature  pH           Dissolved  Hardness    Methoda  Test duration           Parameterb        Concentration  Reference
                  (°C)                      oxygen     (mg/litre                                                      (mg/litre)
                                            (mg/litre) CaCO3)

    Freshwater Organisms

    Daphnia       19 ± 1       8.2                     199         R        16 days                 NOEC (growth)     0.16           De Neer et
    magna                                                          (48 h)                                                            al. (1988)
                  19 ± 1       8.2 ± 0.3               199         R        21 days                 NOLC              10c            Hermens
                                                                                                    NOEC (repro)      3.2c           (1984)
                                                                                                    NOEC (growth)     3.2c

    Ceriodaphnia  25 ± 1       8.18 ± 0.04             57.1 ± 4.1  R        4 days                  NOEC (repro)      4c             Oris et al.
    dubia                                                          (48 h)   7 days                  NOEC (survival)d  4c             (1991)

    Brachydanyo   24 ± 1       6.1-6.5      6.4-8.5    57-61       R        3 months (adults)       NOLC              4.9            Razani et
    rerio                                                          (24 h)                                                            al. (1986b)
                                                                                                    NOEC (spawning)   < 2.2
                                                                   R        2 months (test started  NOEC (growth)     2.2
                                                                   (48 h)   with eggs from adults   NOLC              < 2.2
                                                                            exposed to same
                                                                            concentrations; all
                                                                            eggs hatched after
                                                                            2-3 days)

    Table 12 (contd).

    Organism      Temperature  pH           Dissolved  Hardness    Methoda  Test duration           Parameterb        Concentration  Reference
                  (°C)                      oxygen     (mg/litre                                                      (mg/litre)
                                            (mg/litre) CaCO3)

    Carassius     19-24        7.78         6.2-9.0    197.5       CF       8 days after hatching   LC1 (at hatch)    0.002c         Birge et
    auratus                                                                 (test was started with                                   al. (1979)
                                                                            eggs (1-2 h after
                                                                            spawning) which
                                                                            hatched completely
                                                                            within 3.5 days)

    Pimephales    25 ± 1       8.0          5.3        725.3       CF       30 days after hatching  NOEC (hatching)   83.2c          De Graeve
    promelas                                                                                                                         et al.
                                                                                                    NOEC (growth)     0.75c          (1980)

    Pimephales    25 ± 1       8.0          5.3        725.3       CF                               NOLC              6.1c,e
    promelas      25 ± 2       7.2-7.9      7.7        46.0        CF       38 days after hatching  NOLC              3.57c,f        Holcombe
                                                                            (test was started with  NOEC (growth)     1.83c          et al.
                                                                            eggs within 24 h after  NOEC (hatching)   3.57c,f        (1982)

    Salmo         12-14        7.78         6.2-9.0    197.5       CF       8 days after hatching   LC1 (at hatch)    0.0002c        Birge et
    gairdneri                                                               (test was started with                                   al. (1979)
                                                                            eggs (20 min after
                                                                            fertilization) which
                                                                            hatched completely
                                                                            within 22 days)

    Table 12 (contd).

    Organism      Temperature  pH           Dissolved  Hardness    Methoda  Test duration           Parameterb        Concentration  Reference
                  (°C)                      oxygen     (mg/litre                                                      (mg/litre)
                                            (mg/litre) CaCO3)

                  13.3-14.2    7.4-8.1      8.6-10.2   100         CF       4 days after hatching   NOLC              0.009c,e       Black et
                                                                            (test was started with                                   al. (1983)
                                                                            eggs (20 min after      NOEC (hatching)   0.009c,f
                                                                            fertilization) which
                                                                            hatched within
                                                                            23 days)

                               7.8          5.7        579.9       CF       58 days after hatching  NOEC (growth)     0.1c,g         De Graeve
                                                                            (test was started with                                   et al.
                                                                            eyed eggs which hatched                                  (1980)
                                                                            completely within 48 h)

    a  S = static test; CF = continuous flow test; R = renewal test (semi-static)
    b  NOEC = no-observed-effect concentration = highest tested concentration without observed effect; NOLC = no-observed-lethal concentration.
       An LC1 is a calculated value which is, to some extent, comparable to the observed NOLC value used in other studies.
    c  phenol concentration analysed during test
    d  survival was a more sensitive end-point than reproduction
    e  calculated from results by Task Group
    f  highest concentration tested
    g  extrapolated by authors

         An increase in salinity (0-30%) increased the toxicity of
    phenol to fungi (Babich & Stotzky, 1985).

    9.2  Aquatic organisms

    9.2.1  Freshwater organisms  Short-term studies

         The most important sublethal acute effects observed in
    freshwater species after phenol exposure were a reduced heart rate
    and damage to the epithelium of gills (with loss of function),
    liver, kidneys, intestines and blood vessels. One study reported the
    occurrence of severe seizures, mediated by the central nervous
    system, in  Salmo gairdneri after exposure to sublethal phenol
    concentrations (Bradbury  et al., 1989). In invertebrates, growth
    inhibition was usually observed. Some EC50 values for the latter
    organisms are given in Table 11.

         Most toxicity studies concentrated on lethal effects. Death was
    usually preceded by immobility, loss of equilibrium, paralysis and
    respiratory distress (Razani  et al., 1986a; Tonapi & Varghese,
    1987; Green  et al., 1988; Chagnon & Hlohowskyj, 1989). Toxicity
    testing, where the same species was used by different research
    workers in different waters, resulted in LC50 values (LC50 :
    calculated concentration causing death in 50% of test group) that
    varied widely, as can be seen from Table 11.

         Environmental factors may affect the toxicity of phenol (Brown
     et al., 1967; Miller & Ogilvie, 1975; Ruessink & Smith, 1975;
    Cairns  et al., 1976; Reynolds  et al., 1978; Birge  et al.,
    1979; Dalela  et al., 1980; Gluth & Hanke, 1983; Gupta  et al.,
    1983a,b; Stephenson, 1983). Hardness and pH, however, do not appear
    to have a large impact on phenol toxicity. The toxicity for various
    fungi and fish species, for example, did not change significantly
    over the pH range of 5-8; toxicity for fungi and some fish species
    was not influenced at all by hardness, whereas phenol was slightly
    more toxic in soft than in hard waters for the carp (Herbert, 1962;
    Pickering & Henderson, 1966; EIFAC, 1972; Babich & Stotzky, 1985).
    The effect of temperature appeared to be variable (Cairns  et al.,
    1978; Babich & Stotzky, 1985). Since temperature influences both the
    uptake and the detoxification (conjugation) of phenol (Green  et
     al., 1988), phenol toxicity could be enhanced, as well as
    diminished, by increasing temperature, depending on which parameter
    was influenced most.

         Several biological factors also influence the response of the
    biota to phenol, e.g., strain type, nutritional status, size,
    embryonal or developmental stage, crowding and physiological
    adaptation (Dowden & Benett, 1965; Alexander & Clarke, 1978; Birge
     et al., 1979; Flerov, 1979; De Graeve  et al., 1980; Kordylewska,

    1980; Gupta  et al., 1982b; Mayes  et al., 1982; Black  et al.,
    1983; Lewis, 1983).

         Comparison of 48-h LC50 values from Table 11 shows that, in
    general, fish are the most sensitive freshwater species with respect
    to phenol toxicity. The 48-h LC50 values for some selected fish
    species ranged from 7 to 64 mg/litre. For crustaceans, this range
    was 3.1-200, and for molluscs it was 200-205 mg/litre; for insects,
    it was 19-720 mg/litre and for worms 200-870 mg/litre. Upon
    simultaneous testing of eight species at concentrations up to 51 mg
    phenol/litre, no toxicity was observed for larvae of the amphibian
     Xenopus laevis, for the snail  Aplexa hypnorum or the insect
     Tanytarsus dissimilis. Where toxicity was observed, LC50 values
    were included in Table 11 (Holcombe  et al., 1987). The data
    presented in Table 11 are in good agreement with the order of
    increasing tolerance to phenol proposed by Alekseyev & Antipin
    (1976): fish-crustaceans-tolerant insects-worms-molluscs-highly
    tolerant insects.  Long-term studies

         Most long-term studies with freshwater species have concerned
    growth, reproduction and/or mortality; these studies are discussed
    below. Studies considered to be adequately performed and reported
    are included in Table 12.

         A few long-term studies with freshwater fish have been designed
    to detect sublethal effects of phenol exposure. Increased
    proteolysis as a result of stress, mild kidney damage, and an
    inhibitory effect on the development and maturation of the ovary,
    secondary to a liver dysfunction, were some of the effects reported
    (Dangé, 1986; Gupta & Dalela, 1987; Kumar & Mukerjee, 1988).

         In a life-cycle test using  Daphnia magna, the maximum
    acceptable tolerance concentration (MATC) proved to be 1.5-6.3 mg
    phenol/litre (US EPA, 1980). These results are comparable with the
    no-observed-effect concentration (NOEC) values for growth and
    reproduction (both 3.2 mg phenol/litre) found by Hermens (1984) and
    Oris  et al. (1991). De Neer  et al. (1988), however, found a
    considerably lower NOEC value of 0.16 mg phenol/litre for growth of
     Daphnia magna under similar experimental conditions.

         Exposure of adult  Brachydanio rerio to 2.2, 4.9 or 24 mg
    phenol/litre for 3 months resulted in 67% mortality at the highest
    concentration; the no-observed-lethal concentration (NOLC) was 4.9
    mg phenol/litre. At 24 mg phenol/litre, only immature oocytes were
    found in surviving fish; at the two lower concentrations both
    immature and mature oocytes were observed, whereas spawning was
    delayed. In subsequent embryo-larval tests, starting with the eggs
    of exposed adults, mortality appeared to be maximal during embryonic

    development and the initial larval stage. All larvae died within 12
    days at 4.9 mg phenol/litre. At 2.2 mg phenol/litre, larval
    mortality was still slightly increased, but surviving animals showed
    normal growth and development (Razani  et al., 1986b).

         In two embryo-larval bioassays on  Pimephales promelas, growth
    proved to be the most sensitive criterion: the NOEC values were 0.75
    and 1.83 mg phenol/litre (De Graeve  et al., 1980; Holcombe  et
     al., 1982).

         The results of the embryo-larval test on  Salmo gairdneri
    given by Birge  et al. (1979) (LC1:0.2 µg/litre) and Black  et
     al. (1983) (NOEC:9 µg/litre) are much lower than those obtained by
    De Graeve  et al. (1980) (NOECgrowth: 0.1 mg/litre), probably
    because the latter test was started with eyed eggs, whereas the
    former two tests were started with just-fertilized eggs.

         In addition, Birge  et al. (1979) studied the influence of
    phenol in an embryo-larval test on  Carassius auratus and found a
    LC1 of 2.0 µg phenol/litre.

         Dumpert (1987) reported a NOLC value of 10 mg phenol/litre for
    larvae of the amphibian  Xenopus laevis; larval mortality was 100%
    within 3 weeks at 50 mg phenol/litre. Larval growth was slightly,
    but not significantly, retarded at 5 and 10 mg phenol/litre.
    Hatching was normal at all tested concentrations. However, the
    results may not be reliable because test solutions were renewed only
    once a week, whereas aeration may also have contributed to
    undetected loss of phenol. In other embryo-larval bioassays on five
    amphibian species,  Rana ripiens and  Rana catesbeiana were the
    least tolerant. These species exhibited about equal sensitivity to
    phenol (LC1: 1.0 and 1.1 mg phenol/litre, respectively; LC10:
    5.2 and 8.5 mg phenol/litre, respectively (Birge  et al., 1980).

    9.2.2  Marine organisms  Short-term studies

         In acute toxicity studies on some marine organisms
    (crustaceans, worms, snails and fish), the LC50 values ranged from
    8.8-330 mg phenol/litre (see Table 11). In general, the
    sensitivities of marine and freshwater organisms for phenol were

         At a sublethal phenol concentration, activities of some enzymes
    appeared to be decreased in the brain, liver and muscle tissue of
     Sarotherodon mossambicus; this effect was independent of salinity
    (Ravichandran & Anantharaj, 1984).  Long-term studies

         No adequate data are available on long-term toxicity to marine

    9.2.3  Accumulation

         The bioconcentration factor of phenol may be calculated, using
    a log Pow value of 1.46 (pH not stated, see Table 1) and the
    formula log BCF = 0.79 log Pow -0.40 (Veith & Kosian, 1983). This
    yields a bioconcentration factor of 5.7, which is very low and does
    not indicate any potential for bioaccumulation.

         The experimental bioconcentration factors, reported by Hardy
     et al. (1985) for algae, by Erben (1983) for flatworms, by Erben
    (1982) for snails, by Key & Scott (1986) for crabs, and by Call  et
     al. (1980) and Kobayashi & Akitake (1975) for fish, are in
    agreement with the calculated value. Other studies, however,
    reported higher values. The bioconcentration factor for  Daphnia
     magna, as assessed from 14C measurements, was reported to be
    1375 after 24 h, with an estimated half-life upon depuration of 8 h.
    A lower bioconcentration factor (277) was calculated from uptake and
    depuration rate constants (Dauble  et al., 1986). The
    bioconcentration factors for phenol, as determined by 14C
    measurements in a 5-day experiment with activated sludge, in a 24
    h-experiment with the alga  Chlorella fusca, and a 3-day experiment
    with the fish  Leuciscus idus melanotus, were 2200, 200 and 20,
    respectively (Freitag  et al., 1985).

         Uptake was usually complete (the equilibrium level reached)
    within 1-2 days. Initially, excretion was also rapid, but it usually
    slowed down after some hours, and depuration was reported to be
    incomplete. The amount of unchanged phenol still present after 24 h
    in the alga  Scenedesmus quadricauda, for example, was 22% (Hardy
     et al., 1985), whereas radioactivity from 14C showed a retention
    of 80% after 96 h of depuration in the mud crab  Panopeus herbstii
    (Key & Scott, 1986).

         Based on reported and estimated bioconcentration factors for
    aquatic organisms, phenol is not expected to bioaccumulate

    9.2.4  Metabolism

         The metabolism of phenol in fish yields the known phenyl
    conjugates (phenyl sulfate and phenyl glucuronide) and quinol
    sulfate (Kobayashi  et al., 1976; Layiwola & Linnecar, 1981; Nagel,
    1983; Nagel & Urich, 1983; Kasokat  et al., 1987). In the excreta
    of the frog  Rana temporaria, the same metabolites were found after
    phenol injection, together with catechol, catechol sulfate and
    traces of resorcinol.  Xenopus laevis, another amphibian, appeared

    to be unable to glucuronidate phenol, but compensated this by
    increasing the production of other metabolites compared to  Rana
     temporaria (more quinol sulfate and phenyl sulfate, and, in
    addition, resorcinol sulfate) (Beyer & Frank, 1985; Görge  et al.,

         Phenol metabolism may be induced by prior exposure to phenol or
    phenol derivatives, as was observed for sulfate conjugation in the
    clam  Ruditapes phillippinarum (Kobayashi  et al., 1987).

    9.3  Terrestrial organisms

         Phenol may be taken up by, and stored in, the cuticle membranes
    of various plants, such as tomatoes and green pepper fruits, and
    rubber leaves (Shafer & Schönherr, 1985). Labelled phenol was
    demonstrated to be taken up by soybean roots. The label stayed in
    the roots, and was not transported to the shoot, which was
    attributed to the metabolism of phenol by the plant into immobile
    compounds (McFarlane  et al., 1987). Millet seeds appeared to be
    more sensitive to the toxicity of phenolic compounds than lettuce
    and cucumber seeds. The 120-h EC50 value for root elongation
    inhibition in millet was determined to be 120-170 mg phenol/litre
    (Wang, 1986).

         The toxicity of phenols for four earthworm species (Neuhauser
     et al., 1986) was compared with those of other chemicals using two
    standardized tests developed by the EEC, the 2-day contact test and
    the 14-day artificial soil test. Of ten classes of chemicals, phenol
    was the most toxic in the contact test, with LC50 values of
    2.4-10.6 µg/cm2, regardless of species. A lower relative toxicity
    was reported by the same authors using the artificial soil test.


    10.1  Evaluation of human health risks

    10.1.1  Exposure

         The main way in which the general population can be exposed, on
    a long-term basis, to phenol present in ambient air is as a result
    of industrial emissions and various combustion processes. Other
    inhalation sources include the decomposition of organic materials,
    liquid manure, and the atmospheric degradation of benzene.
    Inhalation and dermal exposure may arise from contact with
    contaminated water or consumer products containing phenol. Indirect
    exposure of man through the food chain is not likely to add
    significantly to long-term inhalation exposure, in view of the short
    life-time of the compound in the environment (section 10.2.1.).
    Individuals may ingest phenol via drinking-water from contaminated
    surface water or ground water. Repeated oral exposure may arise from
    the consumption of smoked food items. Endogenous production of
    phenol may be influenced by the diet and exposure to certain drugs
    and other xenobiotics.

         The exposure data available are inadequate to determine the
    degree of exposure of the general population or of specific groups
    at risk, including workers.

         An upper-limit estimate of the daily intake can be made for
    long-term exposure of the general population. In this hypothetical
    case, it is assumed that an individual will be maximally exposed to
    phenol through continuous inhalation of air from a heavily
    industrialized area, with frequent consumption of smoked food items
    with a high phenol content, and of drinking-water containing phenol
    up to the taste threshold. The estimate is summarized in the table

    Source          Quantity of source   Phenol           Phenol intake

    Air             20 m3/day            200 µg/m3        4 mg/day

    Smoked food     200 g/week           70 mg/kg         2 mg/day

    Drinking-water  2 litres/day         300 µg/litre     0.6 mg/day

         Assuming an average body weight of 70 kg, the total daily
    intake of this maximally exposed individual will be 0.1 mg/kg body

    weight per day. The daily intake by the general population can be
    expected to be much less than this figure.

    10.1.2  Toxicity

         Phenol has moderately acute toxicity for animals. The oral
    LD50 for various animal species range from 300 to 600 mg phenol/kg
    body weight, and the LC50 for rats by inhalation is more than 900
    mg phenol/m3.

         In humans, the lowest acutely lethal oral dose was reported to
    be 4.8 g, which is approximately 70 mg/kg body weight. Local, as
    well as systemic, effects have been reported in humans, consisting
    of irritation, necrosis, cardiovascular effects, metabolic acidosis,
    neurological effects and methaemoglobinaemia. Several fatal cases
    have been reported after oral or dermal intoxication. No documented
    cases of death by inhalation of phenol have been found.

         Solutions of phenol are corrosive to the skin and eyes. Phenol
    vapours can irritate the respiratory tract. Phenol is not a skin
    sensitiser in guinea-pigs or humans.

         The most important effects reported in short-term animal
    studies were neurotoxicity, liver and kidney damage, respiratory
    effects and growth retardation. Toxic effects in rat kidney have
    been reported to occur at oral dose levels of 40 mg/kg per day or
    more. Liver toxicity was evident in rats administered at least 100
    mg/kg per day. In a limited 14-day study on rats, an oral NOAEL of
    12 mg/kg per day was reported based on kidney effects. In this
    experiment, miosis (an iris response to light) was inhibited at 4
    mg/kg per day (the lowest dose tested). However, the health
    significance of this finding is not clear. Some biochemical changes
    have been reported to occur in the intestinal mucosa and kidneys of
    mice at dose levels below 1 mg/kg per day. The toxicological value
    of these insufficiently reported biochemical observations is not

         There have been no long-term general toxicity studies in
    animals or adequate epidemiological studies.

         No adequate studies on the reproductive toxicity of phenol have
    been reported. Phenol has been identified as a developmental
    toxicant in studies with rats and mice. In two multiple-dose rat
    studies, NOAELs of 40 mg/kg per day (the LOAEL was 53 mg/kg per day)
    and 60 mg/kg per day (the LOAEL was 120 mg/kg per day) have been
    reported. For the mouse, the NOAEL was 140 mg/kg per day (the LOAEL
    was 280 mg/kg per day).

         There is some evidence that phenol is genotoxic to mammalian
    cells  in vitro. Based on the induction of bone marrow micronuclei
    in several studies with mice, phenol may have genotoxic potential.

         Oral (drinking-water) animal carcinogenicity bioassays did not
    give evidence of a carcinogenic potential of phenol. No animal
    inhalation or adequate dermal carcinogenicity studies are available.
    Two-stage carcinogenicity studies with mice showed that phenol
    applied to the skin does have tumour-promoting activity. Adequate
    human data on carcinogenicity are not available.

    10.1.3  Evaluation

         Accidental high exposure to phenol may cause severe local
    effects, systemic intoxications and even death. The available data
    do not suggest a strong potential for cumulative health effects from
    chronic exposure.

         The lowest NOAELs identified are for kidney and developmental
    effects, and in rats are in the range of 12-40 mg/kg body weight per
    day. The Task Group decided to derive a tolerable daily intake
    (TDI), taking into consideration this range. An uncertainty factor
    of 200 (including factors of 10 for interspecies variation, 10 for
    intraspecies variation, and 2 to account for the limited data base
    on the toxicity of phenol in animals) was considered appropriate. A
    range of 60-200 µg/kg per day was recommended as the upper limit of
    the TDI by the Task Group. As the Task Group's upper-limit estimate
    of human daily intake is 100 µg/kg body weight per day (section
    10.1.1), it can be concluded that the average general population
    exposure to phenol from all sources will be well below this range.

         There remain, however, two reasons for concern. The available
    data suggest that phenol may be genotoxic, and there is insufficient
    data to discount the possibility that phenol is carcinogenic. For
    these reasons, it is particularly important that this evaluation of
    phenol be kept under periodic review.

    10.2  Evaluation of effects on the environment

    10.2.1  Environmental levels

         Once released into the environment, intercompartmental
    transport of phenol may occur by wet deposition from air to sea
    water and surface water and soil, and, as the compound can be
    expected to be highly mobile in soil, by leaching through soil.
    Evaporation will be slow from water and can only be expected
    following contamination of relatively dry soil.

         Phenol, however, is generally not likely to persist in either
    air, sea or surface water, soil or sewage. It readily reacts
    photochemically and is rapidly biodegraded aerobically, mainly to
    carbon dioxide. Anaerobic degradation to carbon dioxide or methane
    also occur. Half-lives will be in the range of several hours for
    photodegradation and in the range of hours to days for aerobic
    biodegradation. Anaerobic biodegradation also occurs, albeit at a

    slower rate. Low removal rates of phenol in ground water and soil
    may occur, e.g., following spills, with subsequent inhibition of the
    microbial populations.

         The scarce environmental exposure data available give some
    support for the above conclusions:

    *    reported ambient air levels are low (< 8 µg/m3 for urban
         areas; < 200 µg/m3 for heavily industrialized areas);
    *    phenol has been detected in rain water;
    *    reported surface water levels are low (< 24 µg/litre);
    *    levels in ground water have only been found at highly
         contaminated sites.

    10.2.2  Toxicity

         Based on reported and estimated bioconcentration factors for
    aquatic organism, phenol is not expected to bioaccumulate
    significantly. The data base on aquatic toxicity is considered
    adequate for evaluation. Phenol is toxic to aquatic organisms: the
    lowest EC50 for water organisms is estimated to be 3.1 mg/litre
    (48-h LC50 for  Ceriodaphnia dubia). The lowest chronic NOEC is
    estimated to be 0.2 µg/litre (8-day LC1 for  Salmo gairdneri).
    Applying the modified US EPA method, an Environmental Concern Level
    of 0.02 µg/litre can be derived for water. In general, fish are the
    most sensitive species and the sensitivities of marine and
    freshwater organisms are similar. Adequate data on plants and
    terrestrial organisms are not available.

    10.2.3  Evaluation

         The scarce exposure data available do not allow any firm
    conclusions with regard to the degree of risk from phenol to either
    aquatic or terrestrial ecosystems. However, in view of the derived
    Environmental Concern Level of phenol for aquatic organisms, it is
    reasonable to assume that these organisms may be at risk in any
    surface or sea water subject to phenol contamination, in spite of
    the rapid degradation of this compound.


         There is a need for the following items:

    a)   further investigation of the  in vivo genotoxicity of phenol;

    b)   more animal toxicology studies, including 90-day oral and
         inhalation studies, carcinogenicity bio-assays by the
         inhalation route, and neurotoxicity and multigeneration
         reproductive toxicity studies (including evaluation in

    c)   assessment of environmental and occupational exposures and
         evaluation of health effects in occupational populations;

    d)   further evaluation of the dose-duration-effect relationships,
         reversibility/persistence and health significance of the
         reported phenol-induced inhibition of the pupillary response to

    e)   further data on the toxicity of phenol for plants and
         terrestrial organisms.


         The carcinogenic risk of phenol was evaluated in 1989 by the
    International Agency for Research on Cancer (IARC, 1989). The
    summary evaluation from the IARC Monograph is reproduced here.


         Phenol is a basic feedstock for the production of phenolic
    resins, bisphenol A, caprolactam, chlorophenols and several
    alkylphenols and xylenols. Phenol is also used in disinfectants and
    antiseptics. Occupational exposure to phenol has been reported
    during its production and use, as well as in the use of phenolic
    resins in the wood products industry. It has also been detected in
    automotive exhaust and tobacco smoke.

    Experimental carcinogenicity data

         Phenol was tested for carcinogenicity by oral administration in
    drinking-water in one strain of mice and one strain of rats. No
    treatment-related increase in the incidence of tumours was observed
    in mice or in female rats. In male rats, an increase in the
    incidence of leukaemia was observed at the lower dose, but not at
    the higher dose. Phenol was tested extensively in the two-stage
    mouse skin model and showed promoting activity.

    Human carcinogenicity data

         In one case-control study of workers in various wood
    industries, an increased risk was seen for tumours of the mouth and
    respiratory tract in association with exposure to phenol; however,
    the number of cases was small and confounding exposures were
    inadequately controlled.

    Other relevant data

         In humans, phenol poisoning can occur after skin absorption,
    inhalation of vapours or ingestion. Acute local effects are severe
    tissue irritation and necrosis. At high doses, the most prominent
    systemic effect is central nervous system depression. Phenol causes
    irritation, dermatitis, central nervous system effects and liver and
    kidney toxicity in experimental animals.

         Phenol induced micronuclei in female mice and sister chromatid
    exchange in cultured human cells. It did not inhibit intercellular
    communication in cultured animal cells. It induced mutation but not
    DNA damage in cultured animal cells. It did not induce recessive
    lethal mutation in Drosophila. It had a weak effect in inducing
    mitotic segregation in  Aspergillus nidulans. Phenol did not induce
    mutation in bacteria.


         There is inadequate evidence for the carcinogenicity of phenol
    in humans.

         There is inadequate evidence for the carcinogenicity of phenol
    in experimental animals.

    Overall evaluation

         Phenol is not classifiable as to its carcinogenicity to humans
    (Group 3)".


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    1.  Identité, propriétés physiques et chimiques et méthodes

         Le phénol se présente sous la forme d'un solide cristallin
    blanc qui fond à 43 °C et se liquéfie par contact avec l'eau. Il
    dégage une odeur âcre caractéristique et possède une saveur forte et
    piquante. Il est soluble dans la plupart des solvants organiques; sa
    solubilité dans l'eau est limitée à la température ambiante;
    au-dessus de 68 °C il est entièrement soluble dans l'eau. Le phénol
    est modérément volatil à la température ambiante. C'est un acide
    faible, et, sous sa forme ionisée, il est très sensible aux
    réactions de substitution électrophile et à l'oxydation.

         On peut recueillir le phénol dans des échantillons prélevés
    dans l'environnement par absorption dans une solution de soude ou
    par adsorption sur un solide. La désorption s'effectue par
    acidification, entraînement à la vapeur et extraction à l'éther (à
    partir des solutions) ou par voie thermique ou en phase liquide
    (lorsqu'il est adsorbé sur un solide). Les méthodes d'analyse les
    plus importantes sont la chromatographie en phase gazeuse avec
    détection par ionisation de flamme ou capture d'électrons ou encore
    la chromatographie liquide à haute performance avec détection en
    lumière ultra-violette. La limite de détection la plus basse qui ait
    été signalée dans l'air est de 0,1 µg par m3. On peut doser le
    phénol dans le sang et les urines; dans les échantillons d'urine, on
    a fait état d'une limite de détection de 0.5 µg/litre.

    2.  Sources d'exposition humaine et environnementale

         Le phénol est un constituant du goudron de houille et il se
    forme au cours de la décomposition naturelle des substances
    organiques. La majeure partie du phénol présent dans l'environnement
    provient cependant de l'activité humaine. Les sources potentielles
    en sont la production et l'utilisation, tel quel ou sous forme de
    dérivés, en particulier de résines phénoliques et de caprolactame,
    les gaz d'échappement, la combustion de bois de construction et la
    fumée de cigarette. Une autre source potentielle est constituée par
    la dégradation atmosphérique du benzène sous l'action de la lumière,
    la présence de phénol dans le purin pouvant également fortement
    contribuer à sa concentration dans l'atmosphère. Les dérivés du
    benzène et du phénol peuvent, par conversion  in vivo, constituer
    une source d'exposition humaine endogène.

         La production de phénol dans le monde s'est montrée
    relativement constante pendant les années 1980, les Etats-Unis
    d'Amérique en étant le premier producteur. Il est principalement
    utilisé pour la fabrication des résines phénoliques, du bisphénol A
    et de la caprolactame. On en connaît également un certain nombre
    d'applications médicales et pharmaceutiques.

    3.  Transport, distribution et transformation dans l'environnement

         Les principales émissions de phénol se produisent dans l'air.
    La majeure partie du phénol présent dans l'atmosphère finit par être
    dégradée par voie photochimique en dihydroxybenzènes, nitrophénols
    et dérivés résultant de l'ouverture du cycle, avec une demi-vie
    estimative de 4 à 5 heures. Une petite quantité est éliminée de
    l'air par dépôt humide (pluie). Le phénol devrait présenter une
    forte mobilité dans le sol mais son transport et sa réactivité
    peuvent être affectés par le pH.

         Le phénol présent dans l'eau et le sol peut être décomposé par
    des réactions abiotiques ainsi que par l'activité microbienne en un
    certain nombre de produits, dont les plus importants sont le dioxyde
    de carbone et le méthane. La part des réactions biologiques dans la
    décomposition globale du phénol dépend de nombreux facteurs tels que
    la concentration, l'acclimatation, la température et la présence
    d'autres composés.

    4.  Concentrations dans l'environnement et exposition humaine

         On ne possède aucune donnée sur la concentration atmosphérique
    du phénol. La concentration de fond est vraisemblablement inférieure
    à 1 ng/m3. Les valeurs en milieu urbain et suburbain varient de
    0,1 à 8 µg/m3 alors que dans les zones où prédominent les sources
    de phénol (zones industrielles) les concentrations signalées peuvent
    être jusqu'à 100 fois plus élevées. On a décelé du phénol dans l'eau
    de pluie, les eaux superficielles et les eaux souterraines mais les
    données sont très rares. On a fait état de concentrations élevées de
    phénol dans des sédiments et des eaux souterraines par suite de
    pollution industrielle.

         Il peut y avoir exposition professionnelle au phénol lors de la
    production de ce produit et de ses dérivés, lors de l'enduction avec
    des résines phénoliques (industrie du bois et métallurgie) et lors
    d'un certain nombre d'autres activités industrielles. La
    concentration la plus élevée qui ait été signalée (jusqu'à 88
    mg/m3) concernait des ouvriers de l'ex-URSS employés à
    l'extinction du coke avec des eaux usées contenant du phénol. La
    plupart des autres concentrations évoquées ne dépassaient 19

         En ce qui concerne la population dans son ensemble, c'est la
    fumée de cigarette et les aliments fumés qui constituent les plus
    importantes sources d'exposition au phénol, si l'on excepte
    l'exposition par voie atmosphérique. L'exposition par l'eau de
    boisson ou la consommation par inadvertance de produits alimentaires
    contaminés devraient rester faibles; le phénol a en effet une odeur
    et une saveur désagréables, ce qui dans la plupart des cas devrait
    alarmer le consommateur.

    5.  Cinétique et métabolisme

         Le phénol est facilement absorbé par toutes les voies
    d'exposition. Après absorption, il se répartit rapidement dans
    l'ensemble des tissus.

         Une fois résorbé, il forme essentiellement des conjugués avec
    l'acide glucuronique et l'acide sulfurique, et, dans une moindre
    mesure, des hydroxylates avec le catéchol et l'hydroquinone. Il y a
    également conjugaison avec les phosphates. La formation de
    métabolites réactifs (4,4-biphénol et diphénoquinone) a été mise en
    évidence lors d'études  in vitro portant sur des neutrophiles et
    des leucocytes humains activés.

         La proportion relative de glucuronides et de sulfo-conjugués
    varie avec la dose et l'espèce animale. Chez le rat, on a observé
    qu'en augmentant la dose de phénol, la formation de sulfo-conjugués
    l'emportait sur celle de glucuro-conjugués.

         C'est essentiellement dans le foie, les poumons et au niveau de
    la muqueuse gastro-intestinale que le phénol est métabolisé. Le rôle
    relatif joué par ces divers tissus dépend de la voie
    d'administration et de la dose.

         Des études  in vivo et  in vitro ont montré que le phénol se
    fixait aux protéines tissulaires et plasmatiques par liaison
    covalente. Certains métabolites du phénol se lient également aux

         C'est principalement par la voie urinaire que la phénol est
    excrété chez l'animal et l'homme. Le taux d'excrétion urinaire varie
    selon la dose, la voie d'administration et l'espèce. Une faible
    proportion est excrétée dans les matières fécales et l'air expiré.

    6.  Effets sur les animaux d'expérience et les systèmes
        d'épreuve in vitro

         Le phénol présente une toxicité aiguë modérée pour les
    mammifères. La DL50 par voie orale varie chez les rongeurs de 300
    à 600 mg de phénol/kg de poids corporel. La DL50 dermique varie
    respectivement de 670 à 1400 mg/kg de poids corporel chez le rat et
    le lapin et pour le rat, la CL50 à 8h. par voie respiratoire est
    supérieure à 900 mg de phénol/m3. Après exposition aiguë, les
    symptômes cliniques sont une hyperexcitabilité neuromusculaire, des
    convulsions graves, une nécrose de la peau et des muqueuses de la
    gorge et l'on note également des effets au niveau des poumons, des
    fibres nerveuses, des reins, du foie et de la pupille (réflexe

         Les solutions de phénol sont agressives pour la peau et les
    yeux. A l'état de vapeur, le phénol peut irriter les voies

    respiratoires. On est fondé à croire que le phénol n'agit pas comme
    sensibilisateur cutané.

         Les effets les plus importants relevés lors d'études à court
    terme sur l'animal consistaient en neurotoxicité, lésions hépatiques
    et rénales, troubles respiratoires et retard de croissance. A des
    doses orales quotidiennes de 40 mg/kg ou davantage on a observé des
    effets néphrotoxiques chez le rat. Chez la même espèce, il y avait
    une évidente hépatotoxicité aux doses supérieures ou égales à 100
    mg/kg/jour. Lors d'une étude limitée de 14 jours sur des rats, on a
    obtenu, pour la dose par voie orale sans effets nocifs observables,
    une valeur de 12 mg/kg/jour, le critère retenu étant les effets sur
    le rein. Dans cette expérience, il y avait encore inhibition du
    myosis (réaction de l'iris à un stimulus lumineux) à la dose
    quotidienne de 4 mg/kg; toutefois, l'importance médicale de cette
    observation demeure incertaine. On a signalé la présence de
    certaines altérations biologiques au niveau de la muqueuse
    intestinale et des reins chez des souris recevant des doses
    quotidiennes inférieures à 1 mg/kg, observation dont l'importance
    toxicologique n'est pas non plus bien claire.

         Il n'y a pas eu d'études satisfaisantes sur la toxicité du
    phénol pour la fonction de reproduction. Toutefois, la toxicité du
    phénol paraît se manifester par son action délétère sur le
    développement du rat et de la souris. Lors de deux études au cours
    desquelles des rats ont reçu des doses multiples de phénol, on a
    obtenu, pour la dose sans effets nocifs observables, une valeur de
    40 mg/kg/jour (pour la dose la plus faible sans effets nocifs
    observables, cette valeur était de 53 mg/kg/jour) et de 60
    mg/kg/jour respectivement (dans ce cas, la dose la plus faible sans
    effets nocifs observables était de 120 mg/kg/jour). Chez la souris,
    la dose sans effets nocifs observables était de 140 mg/kg/jour (dose
    minimale sans effets nocifs observables: 280 mg/kg/jour).

         La plupart des tests de mutagénicité bactérienne ont donné des
    résultats négatifs. Cependant, des épreuves effectuées  in vitro
    sur des cellules mammaliennes ont révélé la présence de mutations,
    de lésions chromosomiques et d'effets sur l'ADN. Le phénol est sans
    effet sur la communication intercellulaire (mesurée par la
    coopération métabolique) dans des cultures de cellules mammaliennes.
    Un certain nombre d'études ont mis en évidence l'induction de
    micro-noyaux dans des cellules de moelle osseuse murine. Toutefois,
    les études sur la souris n'ont pas révélé la présence de
    micro-noyaux à doses plus faibles.

         Deux études de cancérogénicité ont été effectuées sur des rats
    et des souris mâles et femelles à qui l'on administrait du phénol
    mêlé à leur eau de boisson. On n'a observé d'affections malignes (à
    savoir cancers médullaires de la thyroïde, leucémies) que chez les
    rats mâles soumis à de faibles doses. On n'a pas effectué d'études
    de cancérogénicité en bonne et due forme utilisant la voie

    percutanée ou la voie respiratoire. Des études de cancérogénicité en
    deux phases ont montré que le phénol pouvait se comporter comme un
    agent tumoro-promoteur lorsqu'on l'appliquait à plusieurs reprises
    sur la peau de la souris.

    7.  Effets sur l'homme

         Des cas bien documentés d'exposition humaine au phénol par la
    voie percutanée, buccale ou intraveineuse, ont donné lieu à
    l'observation d'effets indésirables très divers. Il a été fait état
    d'une irritation des voies gastro-intestinales après ingestion de
    phénol. Après exposition de la peau, les effets observés localement
    vont d'un blémissement cutané indolore ou d'un érythème à la
    corrosion et à la nécrose profonde. Parmi les effets généraux, on a
    noté les troubles suivants: arythmies cardiaques, acidose
    métabolique, hyperventilation, détresse respiratoire, insuffisance
    rénale aiguë, lésions rénales, urines foncées, méthémoglobinémie,
    troubles neurologiques (notamment des convulsions), choc
    cardio-vasculaire, coma et mort. La dose orale la plus faible qui
    ait entraîné un décès humain était de 4,8 g; la mort est survenue
    dans les 10 minutes.

         Le risque d'intoxication par inhalation de vapeurs de phénol
    est connu depuis longtemps, mais on n'a pas signalé de décès
    consécutif à ce type d'accident. Les symptômes produits par
    l'inhalation de phénol consistent notamment en anorexie, perte de
    poids, maux de tête, vertiges, salivation et coloration foncée des

         Le phénol n'est pas un agent sensibilisateur.

         Le seuil olfactif pour l'homme serait 0,021 à 20 mg/m3 d'air.
    Pour le phénol en solution aqueuse, on a fait état d'un seuil
    olfactif de 9 mg/litre, le seuil gustatif étant de 0,3 mg/litre

         On ne dispose pas de données suffisantes sur le pouvoir
    cancérogène du phénol.

    8.  Effets sur les êtres vivants dans leur milieu naturel

         Lors d'études portant sur une seule espèce de bactéries, on a
    obtenu, pour la CE50 relative à l'inhibition de la croissance, des
    valeurs allant de 244 à 1600 mg de phénol/litre. On a constaté que
    le seuil de toxicité se situait à 64 mg de phénol/litre. Pour les
    protozoaires et les champignons, les valeurs étaient du même ordre
    que pour les bactéries; pour les algues elles étaient un peu
    inférieures. Le phénol est toxique pour les organismes dulçaquicoles
    supérieurs. Pour les crustacés et les poissons, les valeurs les plus
    faibles de la CL50 ou de CE50 se situent entre 3 et 7 mg de
    phénol/litre. Les données concernant la toxicité aiguë du phénol

    pour les organismes marins sont comparables à celles dont on dispose
    au sujet des organismes d'eau douce. Des études à long terme sur des
    crustacés et diverses espèces de poissons ont révélé des différences
    de sensibilité remarquables; c'est ainsi que les valeurs de la CL1
    provenant d'épreuves sur des embryons et des larves de  Salmo et de
     Carassius se sont révélées très inférieures (respectivement 0,2 et
    2 µg de phénol/litre) aux valeurs correspondantes pour d'autres
    espèces de poissons (concentration sans effet létal observable,
    2,2-6,1 mg/litre) et d'amphibiens, ou tirées d'études sur la
    reproduction des crustacés (concentration sans effet létal
    observable, 10 mg de phénol/litre). On ne dispose pas de données sur
    des épreuves à long terme qui auraient été pratiquées sur des
    organismes marins.

         En général le facteur de bioconcentration du phénol chez les
    divers types d'organismes aquatiques est très bas (<1-10) encore
    qu'on ait signalé parfois des valeurs plus élevées (jusqu'à 2200).
    Il est donc vraisemblable que le phénol ne subit pas d'accumulation
    biologique importante.

         Les données dont on dispose au sujet de la destinée et des
    effets du phénol chez les organismes terrestres sont très peu
    nombreuses. La CE50 à 120 h. est de 120 à 170 mg/litre pour le
    millet et lors d'une épreuve par contact, on a obtenu pour la CL50
    chez le lombric, une valeur comprise entre 2,4 et 10,6 µg/cm3.

    9.  Résumé de l'évaluation

    9.1  Santé humaine

         La population dans son ensemble est essentiellement exposée au
    phénol par la voie respiratoire. Par voie orale, il peut y avoir
    exposition répétée par suite de la consommation d'eau de boisson
    contaminée ou d'aliments fumés.

         On ne dispose pas de données suffisantes pour déterminer
    l'ampleur de l'exposition de la population générale, mais on peut
    donner une limite estimative supérieure de l'absorption quotidienne.
    En mettant les choses au pire, on peut considérer que l'exposition
    maximale se produit chez un individu qui inhale en permanence de
    l'air fortement contaminé et consomme souvent des aliments fumés ou
    de l'eau de boisson qui contient du phénol à des concentrations
    atteignant le seuil gustatif. On a calculé que la dose quotidienne
    ingérée maximale totale estimative pour un individu de ce genre
    pesant 70 kg était de 0,1 mg/kg de poids corporel.

         Les valeurs de la dose sans effets nocifs observables obtenues
    par expérimentation animale en prenant comme critères les troubles
    rénaux et les effets sur le développement étaient, chez le rat, de
    l'ordre de 12 à 40 mg/kg de poids corporel et par jour. En utilisant
    un coefficient d'incertitude de 200, on peut recommander comme

    limite supérieure de la dose journalière totale une valeur située
    entre 60 et 200 µg/kg de poids corporel. En prenant pour l'homme une
    dose quotidienne limite de 100 µg/kg de poids corporel, on peut
    conclure que l'exposition de toutes origines au phénol de la
    population dans son ensemble se situe en-dessous de ces valeurs.

         On peut être préoccupé par le fait que, selon certaines
    données, le phénol pourrait être génotoxique et que d'autre part, on
    ne possède pas suffisamment de résultats pour écarter avec certitude
    l'éventualité que le phénol soit cancérogène. L'évaluation de ce
    composé doit être revue périodiquement.

    9.2  Environnement

         Le phénol ne subit probablement pas d'accumulation biologique
    importante. Il est toxique pour les organismes aquatiques; en
    appliquant la méthode modifiée de l'Agence de protection de
    l'environnement des Etats-Unis, on peut considérer que la
    concentration préoccupante de cette substance dans l'environnement
    est de 0,02 µg/litre. On manque de données suffisantes sur son
    action chez les plantes et les organismes terrestres.

         Il peut y avoir transport du phénol d'un compartiment à l'autre
    de l'environnement par dépôt humide ou par lessivage du sol. En
    général, ce composé ne devrait pas persister dans l'environnement.
    Les rares données dont on dispose sur l'exposition ne permettent pas
    d'évaluer le risque qu'il présente pour les écosystèmes aquatiques
    ou terrestres. Toutefois, en tenant compte de la valeur de sa
    concentration préoccupante pour l'environnement aquatique, il est
    raisonnable de considérer qu'en cas de contamination par le phénol
    des eaux de surface ou des eaux marines, il y a un risque pour les
    organismes aquatiques.


    1.  Identidad, propiedades físicas y químicas, métodos analíticos

         El fenol es un sólido cristalino, blanco, que funde a 43 oC y
    se licúa al contacto con el agua. Posee un olor acre característico
    y un sabor ardiente fuerte. Es soluble en la mayor parte de los
    disolventes orgánicos. A temperatura ambiente, su solubilidad en
    agua es limitada; por encima de 68 oC es completamente hidrosoluble.
    El fenol es moderadamente volátil a temperatura ambiente. Es un
    ácido débil y, en su forma ionizada, muy sensible a las reacciones
    de sustitución electrofílica y a la oxidación.

         El fenol se puede obtener a partir de muestras ambientales por
    absorción en una solución de NaOH o en contacto con sorbentes
    sólidos. La desorción se lleva a cabo por acidificación, destilación
    al vapor y extracción con éter (a partir de soluciones) o mediante
    desorción térmica o líquida (a partir de sorbentes sólidos). Las
    técnicas analíticas más importantes son la cromatografía de gases en
    combinación con la detección de ionización por conductor y de
    captura de electrones, y la cromatografía en fase líquida, de alta
    presión, en combinación con la detección por luz ultravioleta. En el
    aire, el límite de detección más bajo que se haya notificado es de
    0,1 µg/m3. Se puede determinar la presencia de fenol en la sangre
    y la orina; en muestras de orina se ha registrado un límite de
    detección de 0,5 µg/litro.

    2.  Fuentes de exposición humana y ambiental

         El fenol es uno de los componentes del alquitrán de hulla y se
    forma durante la descomposición natural de materiales orgánicos. No
    obstante, la mayor parte del fenol presente en el medio ambiente es
    de origen antropogénico. Algunas fuentes potenciales son la
    producción y el uso de fenol y de sus productos, especialmente
    plásticos fenólicos y caprolactama, los gases de escape, la quema de
    leña y el humo de los cigarrillos. Otra fuente potencial es la
    degradación atmosférica del benceno por la influencia de la luz, si
    bien la presencia del fenol en los purines puede asimismo tener
    considerable influencia en sus niveles atmosféricos. Los derivados
    del benceno y del fenol pueden, mediante una conversión  in vivo,
    constituir una fuente de exposición humana endógena a fenol.

         Según parece, la producción mundial de fenol fue bastante
    regular a lo largo del decenio de 1980, en que los Estados Unidos
    fueron el productor más importante. Se usa principalmente como
    materia básica de las resinas fenólicas, del bisfenol A y de la
    caprolactama. También se le conocen algunas aplicaciones médicas y

    3.  Transporte, distribución y transformación en el medio ambiente

         Las principales emisiones de fenol van al aire. La mayor parte
    del fenol existente en la atmósfera se degradará mediante reacciones
    fotoquímicas frente a los dihidroxibencenos, los nitrofenoles y los
    productos de rotura del anillo, con una semivida, estimada en 4 a 5
    hs. Una parte menor desaparecerá del aire por deposición hídrica
    (lluvia). Se piensa que el fenol es móvil en el suelo, pero el pH
    puede influir en el transporte y la reactividad.

         El fenol presente en el agua y el suelo puede degradarse por
    reacciones abióticas, así como por la actividad microbiana, dando
    lugar a un número de compuestos, los más importantes de los cuales
    son el dióxido de carbono y el metano. La proporción entre la
    biodegradación y la degradación general del fenol está determinada
    por múltiples factores, como la concentración, la aclimación, la
    temperatura y la presencia de otros compuestos.

    4.  Niveles ambientales y exposición humana

         No se dispone de datos sobre los niveles atmosféricos de fenol.
    Se supone que los niveles básicos son inferiores a 1 ng/m3. Los
    niveles urbanos y suburbanos oscilan entre 0,1 y 8 µg/m3, mientras
    que se ha notificado que las concentraciones en las zonas próximas
    al foco de emisión (industria) alcanzan magnitudes cien veces
    superiores. Se ha detectado fenol en la lluvia y en las aguas
    superficiales y subterráneas, pero los datos son muy escasos. En
    sedimentos y aguas subterráneas se han notificado niveles elevados
    de fenol debidos a la contaminación industrial.

         La exposición profesional al fenol puede tener lugar durante la
    producción del mismo y de sus derivados, la aplicación de resinas
    fenólicas (industrias maderera y siderúrgica) y algunas otras
    actividades industriales. La concentración más alta (hasta 88
    mg/m3) se ha notificado en relación con trabajadores de la antigua
    Unión Soviética que apagaban el coque con aguas residuales que
    contenían fenol. La mayor parte de las restantes concentraciones
    notificadas no rebasan los 19 mg/m3.

         Para la población en general, el humo de cigarrillo y los
    alimentos ahumados constituyen las fuentes más importantes de
    exposición al fenol, aparte de la exposición a través del aire. La
    exposición a través del agua potable y de los alimentos contaminados
    por inadvertencia probablemente sea baja; el fenol tiene un olor y
    un sabor desagradables, que en la mayor parte de los casos provocan
    el rechazo del consumidor.

    5.  Cinética y metabolismo

         El fenol se absorbe fácilmente por todas las vías de
    exposición. Tras la absorción, la sustancia se distribuye
    rápidamente a todos los tejidos.

         El fenol absorbido se conjuga principalmente con el ácido
    glucurónico y el ácido sulfúrico y, en menor medida, se hidroxila en
    pirocatequina e hidroquinona. También se conjuga con los fosfatos.
    La formación de metabolitos reactivos (4,4-bifenol y difenoquinona)
    se ha demostrado en estudios  in vitro con neutrófilos y leucocitos
    humanos activados.

         Las cantidades relativas de glucurono y sulfoconjugados varían
    según la dosis y la especie animal. Tras aumentar la dosis de fenol,
    se observó en las ratas un cambio de la sulfatación a la

         El hígado, los pulmones y la mucosa gastrointestinal
    constituyen los sitios más importantes del metabolismo fenólico. La
    función relativa desempeñada por esos tejidos depende de la vía de
    administración y de la dosis.

         Estudios  in vivo e  in vitro han demostrado la unión
    covalente del fenol con las proteínas tisulares y plasmáticas.
    Algunos metabolitos fenólicos se unen asimismo a las proteínas.

         La excreción por la orina es la principal vía de eliminación
    del fenol en los animales y en los seres humanos. La tasa de
    excreción urinaria varía en función de la dosis, de la vía de
    administración y de la especie. Una parte menor se excreta a través
    de las heces y del aire espirado.

    6.  Efectos en mamíferos de laboratorio y en sistemas de
        prueba in vitro

         El fenol tiene una toxicidad aguda moderada en los mamíferos.
    En los roedores, los valores de la DL50 por vía oral oscilan entre
    300 y 600 mg de fenol/kg de peso corporal. Los valores de la
    DL50por vía cutánea para ratas y conejos oscilan entre 670 y 1400
    mg/kg de peso corporal, respectivamente, y el valor de la CL50 por
    inhalación a las 8 horas en las ratas es superior a los 900 mg de
    fenol/m3. Los síntomas clínicos después de la exposición aguda son
    hiperexcitabilidad neuromuscular y convulsiones graves, necrosis de
    la piel y de las mucosas de la garganta y efectos en los pulmones,
    fibras nerviosas, riñones, hígado y en la respuesta pupilar a la

         Las soluciones de fenol son corrosivas para la piel y los ojos.
    Los vapores de fenol pueden irritar las vías respiratorias. Existen
    pruebas de que el fenol no produce sensibilización cutánea.

         Los efectos más importantes notificados a partir de estudios de
    corta duración en animales fueron neurotoxicidad, lesiones hepáticas
    y renales, trastornos respiratorios y retraso del crecimiento. Se
    han notificado efectos tóxicos en el riñón de las ratas con dosis
    por vía oral de 40 mg/kg al día o más. La toxicidad en el hígado
    resultó evidente en las ratas a las que se habían administrado al
    menos 100 mg/kg diarios. En un estudio limitado de 14 días de
    duración realizado en ratas se notificó un nivel sin efectos
    adversos observados (NOAEL) de 12 mg/kg al día por vía oral, basado
    en los efectos renales. En este experimento, la miosis (respuesta
    del iris a la luz) se mantuvo inhibida con 4 mg/kg al día; sin
    embargo, no está claro el significado médico de este hallazgo. Se
    notificó la existencia de algunos cambios biológicos en la mucosa
    intestinal y los riñones de ratones con dosis inferiores a 1 mg/kg
    al día, dato de significado toxicológico incierto.

         No hay estudios adecuados sobre la toxicidad reproductiva del
    fenol. En estudios con ratas y ratones el fenol ha sido identificado
    como tóxico del desarrollo. En dos estudios de dosis múltiples en
    ratas, se han notificado NOAEL de 40 mg/kg al día (el más bajo nivel
    sin efectos adversos observados (LOAEL) fue de 53 mg/kg al día) y de
    60 mg/kg al día (el LOAEL fue de 120 mg/kg al día). En el ratón, el
    NOAEL fue de 140 mg/kg al día (el LOAEL fue de 280 mg/kg al día).

         La mayor parte de las pruebas de mutagenicidad bacteriana han
    dado resultados negativos. En células  in vitro de mamíferos se han
    observado mutaciones, lesiones cromosómicas y efectos en el ADN. El
    fenol no tiene efectos en la comunicación intercelular (medida como
    cooperación metabólica) en cultivos de células de mamíferos. En
    algunos estudios se ha observado la inducción de micronúcleos en
    células de médula ósea de ratones. Con dosis más bajas no se
    observaron micronúcleos en estudios con ratones.

         Se han llevado a cabo dos estudios de carcinogenicidad con
    ratas y ratones machos y hembras a los que se administró fenol con
    el agua de beber. Sólo se observó malignidad (por ejemplo, carcinoma
    de células C de la tiroides y leucemia) en ratas macho con dosis
    bajas. No se han realizado estudios adecuados de carcinogenicidad
    por vía dérmica o por inhalación. Estudios de carcinogenicidad de
    dos fases han mostrado que el fenol, aplicado repetidamente a la
    piel del ratón, tiene efectos activadores. 

    7.  Efectos en el ser humano

         Se ha notificado una larga serie de efectos adversos en el ser
    humano resultantes de la exposición bien documentada al fenol por
    vía cutánea, oral o intravenosa. Se ha notificado irritación
    gastrointestinal tras su ingestión. Los efectos locales de la
    exposición cutánea van desde el emblanquecimiento o el eritema
    indoloros hasta la corrosión y la necrosis profunda. Entre los
    efectos sistémicos cabe citar disritmias, acidosis metabólica,

    hiperventilación, disnea, insuficiencia renal aguda, lesiones
    renales, orinas oscuras, metahemoglobinemia, trastornos neurológicos
    (incluidas convulsiones), choque cardiovascular, coma y muerte. La
    dosis mínima reportada como causante de muerte en el ser humano es
    de 4,8 g por ingestión; la muerte se produjo en menos de 10 minutos.

         Durante mucho tiempo se ha reconocido la posibilidad de
    envenenamiento por inhalación de los vapores de fenol, pero no se
    han reportado casos mortales relacionados con esta vía de
    exposición. Los síntomas que se asocian a la inhalación de fenol
    consisten, entre otros, en anorexia, pérdida de peso, dolor de
    cabeza, vértigo, salivación y orinas oscuras.

         El fenol no es un agente sensibilizante.

         El umbral de percepción del fenol por el olfato humano oscila
    entre 0,021 y 20 mg/m3 en el aire. Se ha notificado un umbral de
    percepción del fenol en el agua de 7,9 mg/litro, y un umbral de
    percepción por el gusto de 0,3 mg/litro en el agua.

         No se dispone de datos adecuados sobre la carcinogenicidad del
    fenol en el ser humano.

    8.  Efectos en los seres vivos del medio ambiente

         En estudios con bacterias de especie única, los valores de la
    CE50 con inhibición del crecimiento oscilaron entre 244 y 1600 mg
    de fenol/litro. Se comprobó un umbral de toxicidad de 64 mg de
    fenol/litro. Los valores para los protozoarios y los hongos fueron
    de la misma cuantía que para las bacterias, mientras que para las
    algas fueron ligeramente inferiores.

         El fenol es tóxico para los organismos superiores de agua
    dulce. Los valores más bajos de la CL50 o la CE50, para
    crustáceos y peces se sitúan entre 3 y 7 mg de fenol/litro. Los
    datos sobre la toxicidad aguda para organismos marinos son
    comparables a los correspondientes a organismos de agua dulce. En
    estudios de larga duración sobre especies de crustáceos y de peces
    se han observado notables diferencias de sensibilidad; los valores
    de la CL1 en pruebas con embriones y larvas de  Salmo y
     Carassius resultaron mucho más bajos (0,2 y 2 µg de fenol/litro,
    respectivamente) que los valores correspondientes a otras especies
    de peces (NOLC de 2,2-6,1 mg/litro) y anfibios, o que los obtenidos
    en pruebas de reproducción en crustáceos (NOLC de 10 mg de
    fenol/litro). No se dispone de datos acerca de pruebas de larga
    duración realizadas en organismos marinos.

         Los factores de bioconcentración del fenol en diversos tipos de
    organismos acuáticos son en general muy bajos (< 1-10), aunque se
    han notificado también algunos valores más altos (hasta 2200). Así
    pues, no se prevé que la bioacumulación del fenol sea significativa.

         Los datos sobre el destino y los efectos del fenol en
    organismos terrestres son muy escasos. En el mijo se determinó una
    CE50 a las 120 horas de 120-170 mg/litro mientras que, en una
    prueba de contacto, la CL50 para especies de lombrices resultó ser
    de 2,4-10,6 µg/cm2.

    9.  Resumen de la evaluación

    9.1  Salud humana

         La población en general está expuesta al fenol principalmente
    por inhalación. La exposición repetida por vía oral puede producirse
    por el consumo de alimentos ahumados o de agua potable.

         No existen datos suficientes para determinar el grado de
    exposición de la población en general, pero se puede calcular la
    cantidad máxima ingerida diariamente. Basándose en "la peor de las
    hipótesis" se puede realizar una estimación suponiendo que un
    individuo estará expuesto en grado máximo al fenol mediante la
    inhalación continua de aire intensamente contaminado acompañada de
    un consumo frecuente de productos alimenticios ahumados y de agua
    que contenga fenol hasta niveles de percepción por el gusto. En
    total, la ingesta máxima diaria de fenol en un individuo de 70 kg se
    calcula en 0,1 mg/kg de peso corporal al día.

         Los valores de NOAEL más bajos identificados en experimentos
    con animales se refieren a efectos en el riñón y en el desarrollo, y
    en las ratas se sitúan dentro de un margen de variación de 12-40
    mg/kg de peso corporal al día. Utilizando un factor de incertidumbre
    de 200, se recomienda como límite máximo de la ingesta diaria total
    (IDT) entre 60 y 200 µg/kg de peso corporal al día. Teniendo en
    cuenta que el límite máximo de la ingesta diaria en seres humanos se
    calcula en 100 µg/kg de peso corporal al día, se llega a la
    conclusión de que la exposición media de la población en general al
    fenol, sea cual fuere la fuente, se encuentra por debajo de este

         Son motivo de preocupación algunas indicaciones de que el fenol
    podría ser genotóxico y el hecho de que no haya datos suficientes
    para descartar con seguridad la posible carcinogenicidad del
    compuesto. La evaluación debe mantenerse sujeta a revisión

    9.2  Medio ambiente

         No se prevé una bioacumulación importante del fenol. Este
    compuesto es tóxico para los organismos acuáticos; mediante la
    aplicación del método modificado de la Agencia de los EE.UU. para la
    Protección del Medio Ambiente, se puede determinar un nivel en medio
    ambiente de preocupación de 0,02 µg/litro. Se carece de datos
    adecuados sobre plantas y organismos terrestres.

         El transporte de fenol entre compartimientos se produce
    principalmente por deposición hídrica y filtración a través del
    suelo. En general, es poco probable que el compuesto persista en el
    medio ambiente. La escasez de datos sobre la exposición no permiten
    evaluar el riesgo que representa el fenol para los ecosistemas tanto
    acuáticos como terrestres. Sin embargo, habida cuenta del nivel de
    preocupación ambiental que se ha establecido en relación con el
    agua, es razonable suponer que los organismos acuáticos pueden
    correr riesgo en cualquier agua superficial o marina contaminada con

    See Also:
       Toxicological Abbreviations
       Phenol (HSG 88, 1994)
       Phenol (ICSC)
       PHENOL (JECFA Evaluation)
       Phenol (PIM 412)
       Phenol (IARC Summary & Evaluation, Volume 71, 1999)