Health and Safety Guide No. 100






    This is a companion volume to Environmental Health Criteria 168:

    Published by the World Health Organization for the International
    Programme on Chemical Safety (a collaborative programme of the United
    Nations Environment Programme, the International Labour Organisation,
    and the World Health Organization)

    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

    WHO Library Cataloguing in Publication Data

    Cresols: health and safety guide.

         (Health and safety guide ; no. 100)

         1.Cresols - adverse effects  2.Anti-infective agents
         3.Occupational exposure 4.  I.Series

         ISBN 92 4 151100 1          (NLM Classification: QD 341.P5)
         ISSN 0259-7268

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    (c) World Health Organization 1996

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    that are not mentioned.  Errors and omissions excepted, the names of
    proprietary products are distinguished by initial capital letters.




         1.1. Identity
         1.2. Physical and chemical properties
         1.3. Analysis
         1.4. Production and uses


         2.1. Environmental fate
         2.2. Exposure
         2.3. Uptake, metabolism, and excretion
         2.4. Effects on organisms in the environment
         2.5. Effects on experimental animals and  in vitro test systems
         2.6. Effects on humans


         3.1. Human health
         3.2. Environment


         4.1. Human health hazards, prevention and protection, first aid
               4.1.1. Information for physicians
               4.1.2. Health surveillance advice
         4.2. Explosion and fire hazards
               4.2.1. Explosion hazards
               4.2.2. Fire hazards
         4.3. Storage
         4.4. Transport
         4.5. Spillage
         4.6. Disposal




         7.1. Exposure limit values
         7.2. Specific restrictions
         7.3. Labelling, packaging, and transport
         7.4. Waste disposal



    The Environmental Health Criteria (EHC) monographs produced by the
    International Programme on Chemical Safety include an assessment of
    the effects on the environment and on human health of exposure to a
    chemical or combination of chemicals, or physical or biological
    agents. They also provide guidelines for setting exposure limits.

    The purpose of a Health and Safety Guide is to facilitate the
    application of these guidelines in national chemical safety
    programmes. The first three sections of a Health and Safety Guide
    highlight the relevant technical information in the corresponding EHC.
    Section 4 includes advice on preventive and protective measures and
    emergency action; health workers should be thoroughly familiar with
    the medical information to ensure that they can act efficiently in an
    emergency. Within the Guide is a Summary of Chemical Safety
    Information which should be readily available, and should be clearly
    explained, to all who could come into contact with the chemical. The
    section on regulatory information has been extracted from the legal
    file of the International Register of Potentially Toxic Chemicals
    (IRPTC) and from other United Nations sources.

    The target readership includes occupational health services, those in
    ministries, governmental agencies, industry, and trade unions who are
    involved in the safe use of chemicals and the avoidance of
    environmental health hazards, and those wanting more information on
    this topic. An attempt has been made to use only terms that will be
    familiar to the intended user. However, sections 1 and 2 inevitably
    contain some technical terms. A bibliography has been included for
    readers who require further background information.

    Revision of the information in this Guide will take place in due
    course, and the eventual aim is to use standardized terminology.
    Comments on any difficulties encountered in using the Guide would be
    very helpful and should be addressed to:

    The Director
    International Programme on Chemical Safety
    World Health Organization
    1211 Geneva 27



    1.1  Identity

    Common name:             Cresols ( o, m, p-isomers)

    Common structure:


          o-cresol                m-cresol               p-cresol

    Common synonyms:

         2-methyl phenol        3-methyl phenol       4-methyl phenol
         2-hydroxy toluene      3-hydroxy toluene     4-hydroxyl toluene
          o-cresylic acid         m-cresylic acid        p-cresylic acid
          o-kresol (German)       m-kresol (German)      p-kresol(German)

    Chemical formula:        C7H8O

    Common trade name:       cresylic acid (mixture of the three isomers)
                             cresylic acids (mixture of phenols)
                             tricresol (mixture of  o, m, p- isomers)
                             dicresol (mixture of  m- and  p- isomers)
                             lysol (mixture of 60 cresol: 40 soap)

    CAS registry

         95-48-7                109-39-4              106-44-5
         ( o-cresol)             ( m-cresol)            ( p-cresol)

    RTECS number:

         G06300000              G06125000             G06475000

    molecular mass:          108.14

    Conversion factors:      air at 25C:             1 ppm = 4.42 mg/m3
                                                      1 mg/m3 = 0.23 ppm

                             water:                   1 ppm = 1 mg/litre

                             solid or
                               semi-solid:            1 ppm = 1 mg/kg

    1.2  Physical and Chemical Properties

    Cresols are isomeric substituted phenols with a methyl substituent at
    one of the  o-, m-, or  p- positions relative to the OH-group.
    Physically, they are white crystalline solids or yellowish liquids
    with a strong phenol-like odour. The compounds are highly flammable,
    moderately soluble in water and soluble in ethanol, ether, acetone, or
    alkali hydroxides. Chemically, these alkylphenols undergo electro-
    philic substitution reactions at the vacant  o- or  p-positions 
    or undergo condensation reactions with aldehydes, ketones, or dienes.

    Physical and chemical data on cresols are presented in the Summary of
    Chemical Safety information (section 6).

    1.3  Analysis

    Cresols can be detected and quantified in a number of environmental
    media and biological samples. The most commonly used methods for
    determining the presence of cresols are gas chromatography-mass
    spectrophotometry (GC-MS) and high-performance liquid chromatography
    (HPLC). Sample detection limits are 1.33 ng/m3 for air;
    4-10 g/litre for water; 300 g/kg for soil and 0.5-1.0 mg/litre for
    urine. Air odour thresholds were reported to be 1.4-22, 0.007-1.2, and
    0.002-0.04 mg/m3 for  o-, m-, and  p-cresol, respectively.

    1.4  Production and Uses

    Cresols and cresol derivatives occur naturally in the oils of various
    flowering plants and trees, such as jasmine, easter lily, yucca,
    conifers, oaks, and sandalwoods.  p-Cresol is found in the urine of
    animals and humans. Commercially, cresols are produced as by-products
    in the fractional distillation of crude oil and coal tars and in coal
    gasification. They are also formed as by-products during the
    combustion of wood, coal, and cigarettes. The various isomers can be
    manufactured by the methylation of phenols, toluene sulfonation and
    alkaline hydrolysis, or the hydrolysis of 2-isopropyltoluene or
    alkaline chlorotoluene. Worldwide production is not known; annual
    production in the USA for 1990 was reported to be 38.3 million kg.

    Cresols have a wide variety of uses as solvents, disinfectants, or
    intermediates in the preparation of numerous products. They are
    commonly used in the production of fragrances, antioxidants, dyes,
    pesticides, and resins. In addition,  p-cresol is used in the
    production of lubricating oils, motor fuels, and rubber polymers,
    while  m-cresol is also used in the manufacture of explosives.


    2.1 Environmental Fate

    Environmental transport of cresols occurs through the vapour phase of
    the atmosphere and from the atmosphere to surface water and soil by
    rain-scavenging. Because of their volatilization, binding to sediment,
    and biodegradation, only small amounts of cresols are found in water.
    In soils, cresols are slightly to highly mobile, depending on the
    Koc value of the soil. Cresols have been detected in groundwater;
    therefore leaching does occur in soil.

    2.2  Exposure

    Exposure to cresols can occur through air, water, or food. The median
    air concentration of  o-cresols was 1.578 g/m3 (0.359 ppb) for 32
    source dominated sites in USA. In the USA, surface water
    concentrations ranged from below detection limits to 77 g/litre.
    Levels of 204 g/litre were reported in Japan in a river polluted from
    industrial effluents. Concentrations as high as 2100 g/litre for
     o-cresol and 1200 g/litre for mixed  m- and  p-cresols have been
    detected in waste waters. Concentrations of all three isomers in
    groundwater from undefined sources ranged from below detection limits
    to 100 mg/litre. Rainwater concentrations ranged from 240 to
    2800 ng/litre for  o-cresol and 380 to 2000 ng/litre for  p- and
     m-cresol combined. Cresols have been detected in foods and
    beverages. Concentrations in spirit beverages ranged from 0.01 to
    0.2 mg/litre. The amount in tobacco smoke was 75 g/85-mm, non-filter,
    American cigarette. The general population can be exposed to cresols
    through air inhalation, drinking-water, food, and beverage ingestion,
    and dermal contact. In general, the lack of adequate monitoring data
    makes the quantitative estimate of daily intakes of cresol from these
    sources impossible. Occupational exposure levels in air as high as
    5.0 mg/m3 have been reported.

    2.3  Uptake, Metabolism, and Excretion

    Cresols are absorbed across the respiratory and gastrointestinal
    tracts and through the skin. The rate and extent of absorption of
    cresols have not been studied specifically; however, studies have
    shown that both gastrointestinal and dermal absorption are rapid and
    extensive. Cresols are distributed to all the major organs. The
    primary metabolic pathway for cresols is conjugation with glucuronic
    acid and inorganic sulfate. Minor metabolic pathways for cresols
    include hydroxylation of the benzene ting and side-chain oxidation.
    The main route of elimination of cresols from the body is renal
    elimination in the form of conjugates.

    2.4  Effects on Organisms in the Environment

    Observations on microorganisms, invertebrates, and fish are available
    and show that cresols may represent a risk to non-mammalian organisms
    at point sources with high cresol concentrations, but not in the
    general environment.

    2.5  Effects on Experimental Animals and In Vitro Test Systems

    Acute poisoning with cresol vapours is unlikely due to the low vapour
    pressure of these compounds. Mean lethal concentrations of cresols for
    rats have been reported to be 29 mg/m3 for  o- and  p-cresols and
    58 mg/m3 for  m-cresols. Oral LD50 values in rats have been
    reported to be 121, 207, and 242 mg/kg body weight for  o-, p-, and
     m-isomers, respectively. Inter-species comparisons show that all
    three isomers are more toxic for mice than for rats and that toxicity
    increases with concentration. Systemic toxicity and death can result
    from dermal exposure. Dermal LD50 values in rabbits were 890, 2830,
    300, and 2000 mg/kg body weight for  o-, m-, p-, and mixed cresols,
    respectively. In rats, dermal LD50 values were 620, 1100, 750, and
    825 mg/kg body weight for  o-, m-, p-, and dicresol, respectively.

    Cresols are highly irritating to the skin and eyes of rabbits, rats,
    and mice.

    Short-term exposure to inhaled mixtures of  o-cresol aerosol and
    vapours resulted in irritation of the respiratory tract, small
    haemorrhages in the lung, body weight reduction, and degeneration of
    heart muscle, liver, kidney, and nerve cells. Short-term (28-days)
    oral exposure to approximately 800 mg/kg body weight per day and above
    resulted in reduced body weights, organ weight changes, and
    histopathological changes in the respiratory and gastrointestinal
    tracts of rats. In mice similarly exposed to 1500 mg/kg body weight,
    more severe effects were reported and, at the highest concentrations,
    death resulted from exposure to  o-, and  m-, and  p-cresols, but
    not from exposure to mixtures of the isomers.

    Exposure of rats to vapours of  o-, m-, or  p-cresol for up to 4
    months resulted in weight loss, reduced locomotor activity,
    inflammation of nasal membranes and skin, and changes in the liver.
    Oral exposures of up to 13 weeks of mice, rats, and hamsters resulted
    in mortality, tremors, reduced body weights, haematological effects,
    increased organ weights, and hyperplasia of nasal, and forestomach

    Oral and inhalation exposures to cresol isomers have resulted in
    lengthened estrus cycles, and histopathological changes in the uterus
    and ovaries of rats and mice. No adverse effects were observed on
    spermatogenesis in rats or mice. Mild letotoxic effects have been

    reported in rats and rabbits exposed to  o-, and  p-cresols, but
    only minor treatment-related developmental effects have been reported.
    Some evidence of genotoxicity has been reported in  in vitro studies
    with  o- and  p-cresols but not  m-cresol. No positive results were
    obtained in  in vivo studies; however, some evidence of promotive
    activities in skin has been reported. No studies of carcinogenicity
    have been reported for any cresol isomers.

    2.6  Effects on Humans

    Ingestion of cresols results in burning of the mouth and throat,
    abdominal pain, and vomiting. Target organs of ingested cresols in
    humans are the blood and kidneys and effects on the lungs, liver,
    heart, and central nervous system have also been reported. In severe
    cases, coma and death may result. Dermal exposure has been reported to
    cause severe skin burns, scarring, systemic toxicity, and death.

    Occupational exposure to cresols usually results from dermal contact.
    Acute exposures have resulted in severe bums, anuria, coma, and death.
    Very few data are available regarding the reproductive effects of
    cresols and no data are available on carcinogenicity in humans.


    3.1  Human Health

    Cresols, at concentrations normally found in the environment, do not
    pose any significant risk for the general population. However, the
    potential for adverse health effects exists for specific
    subpopulations and under conditions of high exposure.

    No information is available regarding the effects of long-term
    exposure to cresols. Thus, information to assess the carcinogenic
    hazard of cresols is inadequate. On the basis of the results of short-
    term studies, an NOAEL of 50 mg/kg body weight per day has been
    identified for all three isomers of cresols. Applying an uncertainty
    factor of 300 was recommended as follows: 10 to account for
    interspecies variation; 10 to account for the lack of long-term
    toxicity studies and possible genotoxic and promoting activity of
    cresols; and 3 to account for intraspecies variation based on the
    rapid and complete metabolism. Thus, an ADI of 0.17 mg/kg body weight
    per day can be developed for cresols.

         NOAEL = 50 mg/kg per day
         Uncertainty factor = 300
         ADI = 0.17 mg/kg body weight per day.

    3.2  Environment

    Observations on microorganisms, invertebrates, and fish show that
    cresols may present a risk for non-mammalian organisms at point
    sources with high cresol concentrations, but not in the general


    4.1  Human Health Hazards, Prevention and Protection, First Aid

    The human health hazards associated with certain types of exposure to
    cresols, together with preventive and protective measures and first
    aid are shown in the Summary of Chemical Safety Information
    (section 6).

    4.1.1  Information for physicians

    High oral or dermal exposure to cresols may rapidly prove fatal.
    Exposed patients should be decontaminated and treated symptomatically.
    Maintenance of breathing and circulation is necessary in cases of
    severe poisoning. There is no specific antidote. Treatment of local
    lesions and systemic intoxication is symptomatic.

    Monitor blood, liver, and kidney functions. Call the nearest Poisons
    Information Centre for further advice.

    4.1.2  Health surveillance advice

    The blood of individuals exposed to cresols on a frequent or long-term
    basis should be examined for haematological changes. Periodic medical
    examinations should also include testing of kidney and liver
    functions, and skin and eye sensitivity or irritation. Special
    attention should be given to pregnant females and females of child-
    bearing age.

    4.2  Explosion and Fire Hazards

    4.2.1  Explosion hazards

    The vapours of cresols may become explosive when exposed to heat or
    flames; the flash-point is approximately 80C. Cylinders containing
    liquid may explode in heat.

    4.2.2  Fire hazards

    Highly flammable and volatile cresols can cause severe toxic effects,
    including burning and irritation of the skin, eyes, and nasal

    4.3  Storage

    Cresols should be stored in well-sealed containers in cool, well-
    ventilated areas, away from sources of ignition.

    4.4  Transport

    Transport should be in well-sealed, protective containers which should
    be labelled indicating the high flammability and corrosive and
    poisonous nature of the substance.

    4.5  Spillage

    In the case of spillage, wear protective gloves and glasses and avoid
    direct contact with skin. Evacuate and ventilate the area. Absorb
    leaking liquid in sand, earth, or inert material, and deposit in
    sealed containers. Collect powdered material in the most convenient
    and safe manner and deposit in a sealable container.

    4.6  Disposal

    Dispose of as hazardous waste.


    Cresols are present in the environment in the air, water, and soil,
    and may undergo rapid chemical and biological transformation. It is
    unlikely that cresols bioaccumulate in the environment or food chain.

    Cresols are moderately toxic for aquatic bacteria, algae, and
    protozoa. The acute toxicity of cresols for invertebrates is low to
    moderate. Cresols have also been shown to be toxic for fish and birds.

    Contamination of the environment can be reduced by controlling
    emissions from industrial point sources. In addition, proper methods
    for the storage, transport, and waste disposal of cresols are
    recommended to reduce the incidence of accidental releases of cresols
    into the environment.


     This summary should be easily available to all health workers
     concerned with, and users of, cresols. It should be displayed at, or
     near, entrances to areas where there is potential exposure to
     cresols, and on processing equipment and containers. The summary
     should be translated into the appropriate language(s). All persons
     potentially exposed to the chemical should also have the instructions
     in the summary clearly explained.

     Space is available for insertion of the National Occupational
     Exposure Limit, the address and telephone number of the National
     Poison Control Centre, and local trade names.

        Cresols ( o, m, p isomers)

    Physical properties                       o-cresol        m-cresol         p-cresol       Other characteristics

    Relative molecular mass                  108.14         108.14          108.14         White crystalline solid or yellowish liquid;
    Melting point (C)                       30.94          12.22           34.74          soluble in ethanol, ethyl ether, acetone,
    Boiling point (C)                       191.0          202.32          201.94         benzene, aqueous alkali hydroxides; pbenolic-
    Water solubility (25C)                  25.95          22.70           21.52          like odour, highly corrosive, and strong
    Relative density (25C)                  1.135          1.030           1.154          irritant; highly reactive with metal (steel,
    Vapour density                           3.7            3.72            3.72           chromium, aluminum) and their alloys;
    Vapour pressure (25C)                   0.31           0.143           0.13           soluble in water
    Flash point (C)                         81             86              86
    Ignition temperature (C)                558            558             558
    Hazard/symptom                           Prevention/protection                         First aid

    Skin: Irritant, corrosive; severe        Protective clothing, gloves, and shoes        Wash immediately with large amount
    burns and scarring                                                                     of water; remove contaminated clothing;
                                                                                           obtain medical care

    Eyes: Corrosive, strong irritant;        Safety glasses                                Wash with water continuously for 30 min;
    lacrimation, redness                                                                   obtain medical care immediately

    Inhalation: Irritation and burning of    Adequate ventilation, use of respirators      Remove from exposure; provide fresh air
    nasal membrane; burning in nose                                                        and adequate ventilation; obtain medical
    and throat                                                                             care

    Ingestion: Irritation and burning of     Store in properly sealed containers;          Rinse mouth; obtain immediate medical care
    mouth, throat, and gastrointestinal      avoid contact with food or beverages
    tract; vomiting

    Environment: Toxic for aquatic and       Avoid environmental releases from
    terrestrial organisms                    industrial processes and accidental spills

    Cresols ( o, m, p isomers) (cont'd)
    Spillage                                   Storage                                       Fire and explosion

    Evacuate and ventilate area; collect       Store away from food and incompatible         Flash-point 81-86C; may be explosive in
    leaking liquid in sealed containers;       materials (metals) in well-labelled           reactions with metals; do not use near open
    absorb liquid in earth, sand, or inert     containers and well-ventilated areas;         fires; poisonous gas may be produced
    material; wear protective clothing         sources of ignition/open flames, and          in a fire
                                               smoking, must be prohibited

    The information in the following table has been extracted from the
    International Register of Potentially Toxic chemicals (IRPTC) legal

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

    7.1  Exposure Limit Values

    Values for exposure limits are given in the following table.

    7.2  Specific Restrictions

    Approved in the USA for use as a pesticide.

    7.3  Labelling, Packaging, and Transport

    In the USA, cresols (all isomers) have been designated as a hazardous
    substance R1987 and must be managed according to federal and/or state
    hazardous waste regulations.

    7.4  Waste Disposal

    In the USA, any sealed waste must be listed as hazardous waste,
    subject to handling, transport, storage, and disposal requirements,
    specified by CERLA, and the Clean Waste Act (effective date 1991).
    These regulations apply to all discharges.

    As a commercial chemical, cresols must be identified as "toxic waste",
    subject to restrictions and disposal regulations, permitting, and
    notification (effective date 1989).

    Any discharge into surface waters requires a permit under the Clean
    Water Act (effective date 1987).

        Exposure limit values
    Medium    Specification      Country/             Exposure limit        Valueb                      Effective
                                 organization         descriptiona                                        date

    Air       occupational       Argentina            8-h TWA               22 mg/m3                      May 1991
                                 Czech Republic       TWA                   20 mg/m3                      1985
                                                      CLV                   40 mg/m3                      1985
                                 Germany              8-h TWA               22 mg/m3                      1991
                                                      5-min STEL            44 mg/m3
                                 Japan                TWA                   22 mg/m3                      1991
                                 Russian              TWA                   0.5 mg/m3                     1989
                                   Federation         CLV                   1.5 mg/m3                     1989
                                 United Kingdom       8-h TWA               22 mg/m3                      1992
                                 USA                  TWA                   22 mg/m3                      1989

    Air       ambient            Russian                                    0.02 mg/m3( m-, p-cresols)     1983
                                   Federation                               0.028 mg/m3 ( o-cresol)

    a  TWA: time-weighted average;
       CLV: ceiling value;
       STEL: short-term exposure limit.
    b  Refers to  o-, m-, p-cresols unless otherwise specified.

    ATSDR (1992)  Toxicological profile for cresols. US Department of
    Health & Human Services, Agency for Toxic Substances and Disease

    CEFIC (1979)  Transport emergency cards for individual products.
    Chemical Industries Association Ltd.

    IPCS (1995)  Environmental Health Criteria 168: Cresols. Geneva,
    World Health Organization.

    IRPTC (1994)  Data profile (legal file) on cresols. Geneva,
    International Register of Potentially Toxic Chemicals.

    Sax NI & Lewis RJ (1989)  Dangerous properties of industrial
     materials, 7th ed. New York, Van Nostrand Reinhold Company.

    US NTP (1992)  Toxicity studies of cresols (CAS nos. 95-48-7,
     108-39-4, 106-44-5) in F344/N rats and B6C3F1 mice (feed studies).
    Research Triangle Park, North Carolina, National Toxicology Program.

    See Also:
       Toxicological Abbreviations
       Cresols (EHC 168, 1995)