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

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

    World Health Organization
    Geneva, 1989

        The International Programme on Chemical Safety (IPCS) is a joint
    venture of the United Nations Environment Programme, the International
    Labour Organization, and the World Health Organization. The main
    objective of the IPCS is to carry out and disseminate evaluations of
    the effects of chemicals on human health and the quality of the
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    epidemiological, experimental laboratory, and risk-assessment methods
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    development of manpower in the field of toxicology. Other activities
    carried out by the IPCS include the development of know-how for coping
    with chemical accidents, coordination of laboratory testing and
    epidemiological studies, and promotion of research on the mechanisms
    of the biological action of chemicals.

    WHO Library Cataloguing in Publication Data

    Chlorophenols other than pentachlorophenol

    (Environmental health criteria; 93)

    1. Chlorophenols     I. Series

    ISBN 92 4 154293 4        (NLM Classification: QV 223)
    ISSN 0250-863X

    (c) World Health Organization 1989

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    1. SUMMARY
         1.1. Identity, physical and chemical properties,
                analytical methods
         1.2. Sources of human and environmental exposure
                1.2.1. Production figures
                1.2.2. Manufacturing processes
                1.2.3. Uses
                1.2.4. Waste disposal
                1.2.5. Release of chlorophenols into the environment
                1.2.6. Natural sources
         1.3. Environmental transport, distribution, and transformation
                1.3.1. Degradation
                1.3.2. Bioaccumulation
                1.3.3. Effects of physical chemical and biological
                         factors on degradation
         1.4. Environmental levels and human exposure
                1.4.1. Chlorophenol levels in the environment
                1.4.2. Chlorophenol levels in food, drinking-water, and
                         treated wood
         1.5. Kinetics and metabolism
         1.6. Effects on organisms in the environment
         1.7. Effects on experimental animals and  in vitro systems
         1.8. Effects on man
                1.8.1. Non-occupational exposure
                1.8.2. Occupational exposure


         2.1. Identity
         2.2. Physical and chemical properties
         2.3. Conversion factors
         2.4. Analytical methods
                2.4.1. Sample collection and storage
                2.4.2. Sample preparation and analysis


         3.1. Natural occurrence
         3.2. Man-made sources
                3.2.1. Production levels and processes
                   World production figures
                   Manufacturing processes

                3.2.2. Uses
                   Wood treatment
                   Water treatment
                   Intermediates in industrial syntheses
                3.2.3. Other sources
         3.3. Waste disposal
         3.4. Losses of chlorophenols into the environment


         4.1. Transport and distribution
                4.1.1. Atmospheric movement
                4.1.2. Soil movement
                4.1.3. Transport in aquatic environments
         4.2. Degradation and bioaccumulation
                4.2.1. Degradation
                   Abiotic degradation
                   Degradation by microorganisms
                4.2.2. Bioaccumulation
         4.3. Effects of other physical, chemical, or biological factors
                4.3.1. pH
                4.3.2. Lack of oxygen
                4.3.3. Inorganic nutrients
                4.3.4. Organic matter
                4.3.5. Temperature
         4.4. Persistence


         5.1. Environmental levels
                5.1.1. Air
                5.1.2. Water
                5.1.3. Soil
                5.1.4. Food and feed, drinking-water
                   Livestock feed
                5.1.5. Treated wood
                5.1.6. Terrestrial and aquatic organisms
                   Other non-human vertebrates

         5.2. General population exposure
         5.3. Occupational exposure


         6.1. Absorption
         6.2. Distribution
                6.2.1. Tissue distribution following chlorophenol
                6.2.2. Tissue distribution following exposure to
                         chemicals metabolized to chlorophenols
         6.3. Metabolic transformation
         6.4. Elimination and excretion


         7.1. Laboratory toxicity studies
                7.1.1. Acute toxicity
                7.1.2. Long-term toxicity
                7.1.3. Organoleptic effects
         7.2. Toxicity studies under natural environment conditions
                7.2.1. Bacteria
                7.2.2. Phytoplankton
                7.2.3. Zooplankton
                7.2.4. Fish
                7.2.5. Effects on physical and chemical variables
         7.3. Treatment levels


         8.1. Acute studies
         8.2. Skin and eye irritation; sensitization
         8.3. Short-term exposure
         8.4. Long-term exposure
         8.5. Reproduction, embryotoxicity, and teratogenicity
         8.6. Mutagenicity and related end-points
         8.7. Carcinogenicity
         8.8. Factors modifying toxicity; metabolism
         8.9. Mechanisms of toxicity, mode of action


         9.1. Acute toxicity
         9.2. Long-term exposure
                9.2.1. Effects on skin and mucous membranes
                9.2.2. Systemic effects
                9.2.3. Psychological and neurological effects
                9.2.4. Reproductive effects

                9.2.5. Carcinogenicity
                   Case-control studies reviewed by IARC
                   Cohort studies reviewed by IAC
                   More recent studies


         10.1. Evaluation of human health risks
                10.1.1. Exposure levels
                  Non-occupational exposure
                  Occupational exposure
                10.1.2. Toxic effects
                10.1.3. Risk evaluation
         10.2. Evaluation of effects on the environment
                10.2.1. Levels of exposure
                10.2.2. Transport
                10.2.3. Degradation
                10.2.4. Bioaccumulation
                10.2.5. Persistence
                10.2.6. Toxic effects on environmental organisms
                10.2.7. Risk evaluation


         11.1. Production
         11.2. Disposal
         11.3. Occupational exposure
         11.4. General population exposure
         11.5. Recommendations for future research
                11.5.1. Environmental Aspects
                11.5.2. Toxicology
                11.5.3. Epidemiology






    Dr U.G. Ahlborg, Unit of Toxicology, National Institute of
        Environmental Medicine, Stockholm, Sweden

    Dr L.A. Albert, Division of Studies on Environmental Pollution,
        National Institute for Research on Biotic Resources, Vera Cruz,
        Mexico  (Vice-Chairman)

    Dr F.A. Chandra, Toxicology and Environmental Health, Department of
        Health and Social Security, London, United Kingdom

    Dr A. Gilman, Industrial Chemicals and Product Safety Section, Bureau
        of Chemical Hazards, Environmental Health Directorate, Department
        of National Health and Welfare, Tunney's Pasture, Ottawa, Canada

    Dr I. Gut, Biotransformation, Institute for Hygiene and Epidemiology,
        Prague, Czechoslovakia  (Chairman)

    Dr R. Jones, Health and Safety Executive, Bootie, Merseyside, United

    Dr J. Kangas, Kuopio Regional Institute of Occupational Health,
        Kuopio, Finland

    Dr E. Lynge, Danish Cancer Registry, Institute of Cancer Epidemiology,
        Copenhagen, Denmark

    Dr U.G. Oleru, Department of Community Health, College of Medicine,
        University of Lagos, Lagos, Nigeria

    Dr J.K. Selkirk, Division of Toxicology Research and Testing,
        Carcinogenesis and Toxicological Evaluation Branch, National
        Institute of Environmental Health Sciences, Research Triangle
        Park, NC, USA

    Dr A. van der Gen, Leiden University, Leiden, Netherlands


    Dr S. Lambert (European Chemical Industry Ecology and Toxicology
        Centre), Rhne Poulenc, Dcines Charpieu, France


    Dr G.C. Becking, Team Leader, International Programme on Chemical
        Safety, Interregional Research Unit, World Health Organization,
        Research Triangle Park, NC, USA  (Secretary)

    Dr T. Kauppinen, International Agency for Research on Cancer, Lyons,

    Mr R. Newhook, Bureau of Chemical Hazards, Environmental Health
        Directorate, Department of National Health and Welfare, Tunney's
        Pasture, Ottawa, Canada  (Temporary Adviser, Rapporteur)


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


        A detailed data profile and a legal file can be obtained from the
    International Register of Potentially Toxic Chemicals, Palais des
    Nations, 1211 Geneva 10, Switzerland (Telephone no. 7988400-7985850).


        A WHO Task Group on Environmental Health Criteria for
    Chlorophenols other than Pentachlorophenol met at the Monitoring and
    Assessment Research Centre, London, United Kingdom, on 21-25 March,
    1988. Dr M. Hutton opened the meeting and welcomed the members on
    behalf of the host institute and on behalf of the United Kingdom
    Department of Health and Social Security, who sponsored the meeting.
    Dr G.C. Becking addressed the meeting on behalf of the three
    Cooperating Organizations of the IPCS (UNEP, ILO, and WHO). The Task
    Group reviewed and revised the draft criteria document and made an
    evaluation of the risks for human health and the environment from
    exposure to chlorophenols other than pentachlorophenol.

        The drafts of this document were prepared by Mr R. NEWHOOK and
    Dr A. GILMAN, Health Protection Branch, Ottawa, Canada. Dr G. BECKING,
    IPCS Interregional Research Unit, was responsible for the overall
    scientific content of the document and Mrs M.O. HEAD, Oxford, England,
    for the editing.

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


        Partial financial support for the publication of this criteria
    document was kindly provided by the United States Department of Health
    and Human Services, through a contract from the National Institute of
    Environmental Health Sciences, Research Triangle Park, North Carolina,
    USA -- a WHO Collaborating Centre for Environmental Health Effects.
    The United Kingdom Department of Health and Social Security generously
    supported the costs of printing.

    1.  SUMMARY

    1.1  Identity, Physical and Chemical Properties, Analytical Methods

        Chlorophenols (CPs) are organic chemicals formed from phenol
    (1-hydroxybenzene) by substitution in the phenol ring with one or more
    atoms of chlorine. Nineteen congeners are possible, ranging from
    monochlorophenols to the fully chlorinated pentachlorophenol (PCB).
    Chlorophenols, particularly trichlorophenols (T3CP), tetrachloro-
    phenols (T4CP), and PCP, are also available as sodium or potassium

        Chlorophenols are solids at room temperature, except for 2-MCP,
    which is a liquid. The aqueous solubility of chlorophenols is low, but
    the sodium or potassium salts of chlorophenols are up to four orders
    of magnitude more soluble in water than the parent compounds. The
    acidity of chlorophenols increases as the number of chlorine sub-
    stitutions increases. The  n-octanol/water partition coefficients
    of chlorophenols increase with chlorination, indicating a propensity
    for the higher chlorophenols to bioaccumulate. Taste and odour
    thresholds are quite low.

        Technical grade chlorophenol products are heterogeneous mixtures
    of chlorophenols, unreacted precursors, and a variety of dimeric
    microcontaminants. As a result of the semiquantitative nature of the
    reaction of chlorine with molten phenol, commercial formulations of
    chlorophenols contain substantial quantities of other chlorophenols.
    When the alkaline hydrolysis of chlorobenzenes is used to manufacture
    chlorophenols, the technical product can contain unreacted

        A number of other compounds are present as microcontaminants in
    technical tri- and tetrachlorophenol preparations, as a result of the
    elevated reaction temperatures used. These include the polychlorinated
    dibenzo- p-dioxins (PCDDs), polychlorinated dibenzofurans (PCDFs),
    polychlorinated phenoxyphenols ("predioxins"), polychlorinated
    diphenyl ethers, polychlorinated benzenes, and polychlorinated
    biphenyls. Lower chlorophenol preparations do not contain detectable
    levels of dioxins, presumably because their manufacture does not occur
    at sufficiently high temperatures. Tri- and tetrachloro-dibenzo-
     p-dioxins predominate in T3CP formulations, while the hexa, hepta,
    and octa congeners are the major PCDD contaminants in technical T4CP
    and PCP. 2,3,7,8-Tetra-chlorodibenzo- p-dioxin (2,3,7,8-TCDD) occurs 
    primarily as a contaminant of 2,4,5,-T3CP, though it is present at
    low g/litre concentrations in T4CP, PCP, and Na-PCP. Chlorophenol
    formulations contain a similar array of PCDFs. Phenoxyphenols may
    comprise as much as 1-5% of the formulation.

        A large number of sampling and analytical methods have been
    developed for the determination of chlorophenols in different media.
    Sensitive methods, such as gas chromatography, high-performance liquid
    chromatography, and mass spectrometry are increasingly used.

    1.2  Sources of Human and Environmental Exposure

    1.2.1  Production figures

        Recent data on production levels of chlorophenols other than PCP
    are not readily available. Around 1975, the combined global production
    of all chlorophenols approached 200 million kg; slightly more than
    half of this quantity consisted of non-PCP chlorophenols, primarily
    2,4-dichlorophenol (2,4-DCP), 2,4,5-trichlorophenol (2,4,5-T3CP),
    and 2,3,4,6-tetrachlorophenol (2,3,4,6-T4CP). Consumption has since
    declined in some countries as a consequence of health-based concerns
    (particularly for 2,4,5-T3CP), and the use of alternative wood
    preservatives. Some European countries and the USA are major producers
    and consumers of chlorophenols.

    1.2.2  Manufacturing processes

        The compounds 2-MCP, 4-MCP, 2,4-DCP, 2,3,4-T3CP, 2,4,6-T3CP,
    2,3,4,6-T4CP, and PCP have been made by direct stepwise chlorination
    of phenol or lower chlorinated phenols at a high temperature; a
    catalyst is necessary if the last two chlorophenols are being
    produced. Alternatively, some chlorophenols (2,5-DCP, 3,4-DCP,
    2,4,5-T3CP, 2,3,4,5-T4CP and PCP) can be produced by the alkaline
    hydrolysis of the appropriate chlorobenzene.

        Both methods yield contaminants that are themselves potential
    health hazards, including polychlorinated dibenzo- p-dioxins (PCDDs),
    polychlorinated dibenzofurans (PCDFs), and 2-phenoxyphenols.

    1.2.3  Uses

        Chlorophenols are toxic for a wide range of organisms, a property
    that accounts for many of their uses. Large quantities of higher
    chlorophenols are used in pressure treatment in the wood preservation
    industry; in addition, substantial amounts of the sodium salts of
    T4CP, PCP, and T3CP are used to surface-treat fresh-cut logs and
    lumber against sapstain fungi and surface mould. Large quantities of
    lower chlorophenols serve as intermediates in the production of
    pesticides, such as T4CP, PCP, 2,4-D, and 2,4,5-T. The use of 2,4,5-T
    has been discontinued in a number of countries. Lesser amounts of
    chlorophenols are used as wood preservatives in agricultural and
    domestic applications, and as additives to inhibit microbial growth in
    a wide array of products, such as adhesives, oils, textiles, and
    pharmaceutical products.

    1.2.4  Waste disposal

        As a result of process design, the quantities of chlorophenolic
    wastes generated are reportedly small. Available treatment methods for
    such waste should prove satisfactory, if they are carefully applied.
    Gravity separation is the primary treatment method most often used to
    recover oil and the associated chlorophenol for recycling and
    treatment. Organisms during secondary treatment degrade roughly 90% of
    most chlorophenol waste, provided that they are acclimated to the
    waste, and precautions are taken against shock loadings. Adsorption
    onactivated carbon as a final clean-up step removes almost 100% of
    remaining waste chlorophenols in waste-streams. Incineration appears
    to be an effective means of disposal, if the temperatures are high
    enough and residence times long enough to ensure complete combustion
    and prevent the formation of PCDDs and PCDFs in the incinerator.

    1.2.5  Release of chlorophenols into the environment

        Patterns of losses to the environment appear similar in most
    industrialized countries. The majority of chlorophenol wastes are
    released in spills and leaching from treated lumber (PCP, NaPCP,
    NaT4CP), and as contaminants or breakdown products of agricultural
    pesticides (2,4-DCP, 2,4,5-T3CP). Substantial amounts of
    chlorophenol wastes (NaT4CP, NaPCP) are released from sawmills,
    planer mills, and the incineration of wood wastes. Significant amounts
    of chlorophenols can be formed and subsequently released into the
    environment from the chlorine bleaching process in pulp and
    paper-mills, the chlorination of waste-water and drinking-water, and
    the incineration of municipal waste. A significant amount of wastes is
    discharged from manufacturing sites. Losses during storage and
    transport are negligible. No estimates are available of the quantities
    of chlorophenols released as a result of the disinfection of
    waste-waters with chlorine, volatilization, or domestic uses of
    products containing these compounds.

    1.2.6  Natural sources

        While some chlorophenols and related organohalogens occur
    naturally, as metabolites of certain flora and fauna, these sources
    are thought to make a negligible contribution to overall environmental

    1.3  Environmental Transport, Distribution, and Transformation

        Chlorophenols adsorb strongly on acidic soils, and those with a
    high organic content. Leaching is more significant in basic and
    mineral soils. Studies to date have not addressed the quantitative
    contribution of these processes to the transport of chlorophenols
     in situ.

        Adsorption appears to play an important role in surface waters.
    Chlorophenols that are not degraded in the water body are incorporated
    into the sediments, most likely because they adsorb on sediment
    particulates. They may persist in sediments for years. However, it is
    not known how important this process is for lower chlorophenols, since
    they should be adsorbed to a lesser extent than the T4CPs and PCP
    studied to date.

        While a large part of the chlorophenols entering natural waters is
    probably degraded, they are nonetheless fairly persistent and, thus,
    may be transported considerable distances by water.

        Although chlorophenols are principally water and soil
    contaminants, some atmospheric movement occurs, and low levels of PCP
    have been found in rain, snow, and outdoor air. No corresponding
    measurements have been made for other chlorophenols, but it is highly
    probable that they too are transported in this manner.

    1.3.1  Degradation

        Chlorophenol residues are removed from the environment by both
    biological and non-biological degradation. Laboratory studies have
    shown that ultraviolet radiation can break down chlorophenols in a
    matter of hours to days, and the shifts in the ratio of PCP to some of
    its breakdown products  in situ suggest that this process is
    important in exposed habitats.

        A large number of bacteria and fungi from different habitats are
    able to degrade chlorophenols in the laboratory, sometimes eliminating
    tens of mg/litre in a matter of hours or days. Degradation is
    generally slowest for the higher chlorinated phenols, and for those
    with a chlorine in the "meta" position. Previous exposure to a given
    chlorophenol or a related compound enables a microorganism to
    metabolize it immediately and/or at a faster rate, presumably by
    inducing the necessary enzymes. In general, anaerobic biodegradation
    of these compounds is much slower than aerobic metabolism.
    Considerable overlap appears to exist in the rates of biodegradation
    of the compounds in different habitats.

        But chlorophenols should only persist in environments where the
    rates of these transformations are minor. The persistence of
    chlorophenols other than PCP has not been studied under controlled
    conditions, but spills and applications of PCP as a herbicide
    reportedly disappear in a matter of weeks or months.

    1.3.2  Bioaccumulation

        Bioaccumulation of chlorophenols appears to be moderate, and most
    bioconcentration factors (BCFs) fall roughly between 100 and 1000. The
    biocentration factor is usually a positive function of the chlorine
    number, and there are no obvious relationships between it and the type
    of organism (algae, plants, invertebrates, fish). Once exposure is
    discontinued, chlorophenols clear rapidly from biota, indicating that
    the bioaccumulation observed in field studies is the result of
    long-term exposure rather than persistence.

    1.3.3  Effects of physical, chemical, and biological factors on

        Both the rate of evaporation and the extent of adsorption of PCP
    (and undoubtedly other chlorophenols) are inversely related to pH. In
    contrast, the rates of photolysis of 4-MCP and 2,4-DCP both increase
    with pH, and shortage of oxygen, inorganic nutrients, or organic
    matter may all influence the biodegradation rate of various lower
    chlorophenols. Higher temperatures increase the rates of evaporation,
    photolysis, and microbial degradation of chlorophenols, although the
    last process obviously has an upper limit.

    1.4  Environmental Levels and Human Exposure

    1.4.1  Chlorophenol levels in the environment

        Data on levels of chlorophenols other than PCP in the environment
    are not available for air. Levels of PCP in outdoor air range from 1
    to several ng/m3. Work-place air concentrations of chlorophenols are
    much higher. Facilities in which chlorophenols are used, such as
    sawmills, often have air levels of several tens of g/m3, while in
    manufacturing facilities, concentrations may be in the mg/m3 range.

        Residues of all chlorophenol isomers have been found in fresh and
    marine waters. In relatively undeveloped areas, levels are often
    undetectable in receiving waters, and only occasionally exceed
    1 g/litre close to industrial sources of chlorophenols. In receiving
    waters from heavily industrialized regions, ambient levels are
    somewhat higher, but still median concentrations do not exceed
    1 g/litre, while the maximum concentrations in surface waters and
    ground waters can reach several g/litre. As a result of spills,
    isolated levels as high as 61 000 g/litre of chlorophenols (T4CP +
    PCP) in ground water, and 18 090 g/litre in surface waters have been

        Levels of some chlorophenols in effluents from chemical and wood
    preservation industries may reach several thousand g/litre, though
    typical levels are in the low g/litre range, and dilution apparently
    reduces these to the observed low ambient levels.

        Chlorophenol concentrations in sediments are generally higher than
    those in the overlying water. Levels in sediments from waters not
    receiving large chlorophenol inputs generally contain less than 1 g
    of the individual chlorophenols/kg dry sediment. The maximum levels of
    all chlorophenol isomers in fresh-water sediments in industrialized
    regions seldom exceed 50 g/kg. However, in some instances, thousands
    of g chlorophenols/kg have been detected in fresh-water sediments
    adjacent to point sources (spillage sites and effluent discharges).

        In waters receiving chlorophenolic wastes, invertebrates generally
    contain from trace levels to 20 g of chlorophenols from the
    surrounding environments/kg wet tissue, though levels approaching
    200 g/kg have been observed in some instances. Fish can contain
    similar whole-body levels of chlorophenols, usually concentrated in
    the liver and viscera. For example, liver tissues from sculpins
    inhabiting polluted waters contained up to 1600 g/kg wet weight. In
    birds, muscle tissues exhibited only trace to moderate (50 g/kg wet
    weight) levels of chlorophenols, however, higher concentrations have
    been found in single samples of liver, brain, kidney, and eggs. For
    instance, a level of 1017 g 2,4-DCP/kg (fresh weight) was found in
    the kidney of an eagle.

    1.4.2  Chlorophenol levels in food, drinking-water, and treated wood

        Quantities of T4CP range from trace to several g/kg in carrots,
    potatoes (also 2,4-DCP), turnips, cabbages, beets, and raw milk,
    though contamination from treated wood storage containers can elevate
    these levels considerably. Recent restrictions on the agricultural use
    of chlorophenols have reduced this contamination. T4CP has been
    detected in poultry, but no reports of residues in other meat have
    been found.

        Drinking-water supplies are characterized by relatively low
    concentrations of chlorophenols. While a variety of congeners have
    been detected, these are usually present in the range of 10-3 to
    10-1 g/litre.

        Concentrations of PCP or T4CP in treated wood are predictably
    high, and can reach several hundred mg/kg of wood dust or shavings.

    1.5  Kinetics and Metabolism

        The lower chlorophenols are readily absorbed across the skin of
    both laboratory animals and human beings. The results of studies on
    rats further suggest that absorption via the skin is greater for the
    sodium salts than for the parent molecules (2,3,5,6-T4CP and its salt
    were used). Ingested chlorophenols are also readily taken up from the
    gastrointestinal tract. The absorption of inhaled lower chlorophenols
    by experimental animals has not been studied.

        Experimental animals accumulate chlorophenols mostly in the liver
    and kidney, and to a lesser extent in the brain, muscle, and fat
    tissues. The higher levels in the liver and kidney may reflect their
    greater circulating blood volume, as well as the role these organs
    play in the detoxification and elimination of these compounds. Related
    compounds, such as trichlorophenyl acetate, 2,4-D, Nemacide, Silvex,
    2,4,5-T, and lindane, yield similar tissue distributions of
    chlorophenol metabolites.

        In the animals studied to date, most chlorophenols were rapidly
    conjugated to glucuronates or sulfates in the liver. This binding, and
    also dechlorination and methylation, serve to detoxify these
    compounds. At present, the only chlorinated phenol that is known to be
    metabolized to a more toxic substance is 2,3,5,6,-T4CP, which gives
    rise to tetrachloro- p-hydroquinone. The corresponding quinone has
    been shown to bind covalently to protein and DNA.

        Chlorophenols are eliminated by test mammals primarily through the
    urine (roughly 80-90%), in both free and bound forms. Smaller amounts
    are eliminated in faecal matter. A single dose of chlorophenols is
    virtually eliminated within one to several days. Elimination rates
    appear to be even more rapid for some tissues.

    1.6  Effects on Organisms in the Environment

        The available information on the effects of chlorophenols in the
    environment centres primarily on aquatic organisms. Considerable
    overlap exists in the concentrations that are toxic for bacteria,
    phytoplankton, plants, invertebrates, and fish, most of the EC50 and
    LC50 values falling in the several mg/litre range. Toxicity generally
    increases with the degree of chlorination of the phenol ring. However,
    chlorophenols with chlorine in the 3 and 5 positions ("meta"
    chlorophenols) are often more toxic than expected solely on the basis
    of their chlorine number. Species-specific sensitivity can override
    these general patterns. Furthermore, particularly in the case of the
    higher chlorophenols, acute toxicity is a strong inverse function of
    pH, reflecting the degree of ionization of the chemical. In long-term
    studies, sublethal levels of 2,4-DCP reduced both growth and survival
    of fathead minnows. In one study, exposure to a concentration of only
    0.5 g 2,4,6-T3CP/litre was fetotoxic in trout.

        Fish kills have resulted from PCP spills, some of which have also
    involved T4CP. In controlled field studies, exposure to large
    quantities (100-5000 g/litre) of chlorophenols (4-MCP, 2,4-DCP,
    2,4,6-T3CP) generally impaired algal primary production and
    reproduction, altered algal species composition dramatically, and

    reduced zooplankton biomass and production. These studies shed little
    light on the hazard, if any, presented by the low-level contamination
    observed in most environments. The low concentrations of several
    chlorophenols typically found in moderately contaminated waters have
    been reported to impair the flavour of fish.

    1.7  Effects on Experimental Animals and  In Vitro Systems

        In rats, lethal doses of lower chlorinated phenols resulted in
    tremors and convulsions (except for T4CP and some T3CPs), hypotonia,
    and, after death, a rapid onset of rigor mortis. Acute LD50s for rats
    for all lower chlorophenols and routes of administration ranged from
    130 to 4000 mg/kg body weight. The range of toxicity of the compounds
    generally occurred in the following order: T4CPs > MCP > DCPs >
    T3CPs, when the toxicant was administered either orally or by
    subcutaneous injection. When injected intraperitoneally, the
    toxicities of MCP, DCPs, and T3CPs were similar, while T4CP was 2-3
    times more toxic. In studies on dermal exposure, 2,3,5,6-T4CP was the
    most toxic of the T4CP isomers. These variations according to route
    of administration may reflect differences in the rate of absorption of
    the compounds. Acute effects are attributable to the parent
    chlorophenol itself rather than to the microcontaminants.

        Some reports have indicated that lower chlorinated phenols cause
    mild irritation of the eye in rats. This effect increases with the
    number of chlorine atoms on the phenol ring. Skin sensitization has
    not been shown for the chlorophenols.

        Short-term exposures of rats and mice to 2,4-DCP at hundreds of
    mg/kg have been consistently associated with increased spleen and
    liver weights and, in some instances, with haematological or
    immunological effects. The very few studies concerning exposure to
    various tri- and tetrachlorophenols have also identified
    exposure-related changes in the weight or histology of the liver and,
    in some instances, of the spleen or kidney. In one study, combined
    pre- and postnatal exposure to 2-MCP and 2,4-DCP resulted in
    haematological changes in exposed rats, but only 2,4-DCP elicited
    immune responses.

        Several lower chlorophenols appear to be mildly fetotoxic, though
    the data are inconsistent in this regard. While female rats exposed to
    2-MCP, 2,4-DCP, or 2,4,6-T3CP in the drinking-water produced smaller
    litters with an increased frequency of stillborn offspring in one
    study, similar or higher exposures in other studies did not have any
    effects on these and other reproductive parameters. A dose of 30 mg/kg
    body weight per day of pure or technical 2,3,4,6-T4CP delayed
    ossification of fetal skull bones, but was not embryolethal.

        Birth defects did not arise as a result of daily exposure of rats
    to concentrations of up to 500 mg 2-MCP/litre, 300 mg 2,4-DCP/litre
    (both in the drinking-water), 1000 mg 2,4,6-T3CP/kg body weight and
    30 mg 2,3,4,6-T4CP/kg body weight (both by gavage).

        Limited information indicates that 2,4,6-T3CP (in yeast and
    mammalian test systems) and 2,3,4,6-T4CP (Chinese hamster cell
    cultures) elicited weak mutagenic responses, but were not clastogenic.
    Most of the other chlorophenols that have been tested have been found
    to be non-mutagenic in the few test systems used (primarily

        Exposure of rats and mice (both sexes) to 2,4-DCP for 2 years at
    doses as high as 440 and 1300 mg/kg body weight per day, respectively,
    proved negative with respect to carcinogenicity. In a test with a
    similar design, 2,4,6-T3CP at doses of up to 10 000 mg/kg body
    weight per day caused cancer in mice (hepatocellular carcinomas or
    adenomas) and male rats (lymphomas, leukaemia). The 2,4,6-T3CP used
    was commercial grade and was not analysed for impurities, such as
    PCDDs and PCDFs.

        Studies on rats on the carcinogenicity of 2-MCP or 2,4-DCP
    (500 g/litre and 300 g/litre, respectively, for 15-24 months) were
    inadequate. Some chlorophenols appeared to be promoters (MCPs,
    2,4-DCP, and 2,4,5-T3CP); others did not.

        Exposure of female rats to 2,4-DCP in the drinking-water, at
    0-300 mg/litre, altered the major immune function in offspring exposed
    prenatally and postnatally, but not in rats exposed only  in utero.
    In contrast, in a similar study, a concentration of 2-MCP as high as
    500 mg/litre did not have any adverse effects on the immune systems of

        The major effects observed with lethal exposures to chlorophenols
    indicated a general effect on the nervous system. Long-term studies
    implicated the liver and kidney as organs that accumulate high
    concentrations of chlorophenols and are often adversely affected by
    exposure to chlorophenols, perhaps reflecting their roles in the
    detoxification and elimination of xenobiotics. On the basis of the
    suppression of cell-mediated immunity in rats exposed to 2,4-DCP, it
    can be assumed that the thymus and spleen may be target organs.

        The toxicology of chlorophenols is complicated by the presence of
    PCDD and PCDF microcontaminants in technical grade products.
    Assessment of toxicity studies with chlorophenols requires a knowledge
    of the types, levels, and effects of the microcontaminants that are
    present in the formulation studied, because some PCDDs and PCDFs are
    extremely toxic.

        The major mode of action in the acute toxicity of chlorophenols
    involves the uncoupling of oxidative phosphorylation and the
    inhibition of the electron transport system. These effects are related
    to the number of chlorine atoms on the molecule and to a lesser extent
    by their positions on the molecule. PCP is 40 times more potent than
    2,4-DCP as an uncoupler. The chlorophenate ion is evidently
    responsible for the uncoupling reaction, while the undissociated
    molecule causes convulsions.

        Other enzyme systems are also inhibited by exposure to
    chlorophenols  in vitro, though, in some instances, such inhibition
    is not observed with  in vivo exposures.

    1.8  Effects on Man

    1.8.1  Non-occupational exposure

        Low (usually 10 mg/kg) levels of the lower chlorinated phenols are
    found in the serum, urine, and adipose tissues of the general
    population. The major identifiable sources of these chlorophenols are
    food and drinking-water. Chlorophenol levels in the ambient atmosphere
    have not been measured.

        In the only instance of acute exposure of the general population
    to chlorophenols, an explosion at a manufacturing plant contaminated
    an area, with a population of 37 000 persons, with sodium hydroxide,
    2,4,5-T3CP, and TCDD. However, the effects, if any, of the released
    2,4,5-T3CP were masked by those of TCDD. Clinical symptoms
    attributed to TCDD were recorded in the exposed individuals. No toxic
    effects have been attributed to the low concentrations of
    chlorophenols typical of most non-occupational exposures. However,
    undesirable organoleptic effects are produced by chlorophenols at very
    low concentrations.

    1.8.2  Occupational exposure

        Worker exposure is a major concern in industries in which
    chlorophenols are used extensively, as respiratory and dermal
    absorption of these compounds results in measurable levels in the
    blood and urine of exposed workers. In the manufacture of
    chlorophenols, clinical symptoms associated with exposure include eye,
    nose, and airway irritation, dermatitis, chloracne, and porphyria.
    Abnormal liver function tests, changes in brain wave activity, and
    slowed visual reaction time have been reported in association with
    high-level exposure.

        In sawmill workers, Na-T4CP exposures have caused numerous cases
    of dermatitis and respiratory irritation. Eye, nose, and airway
    irritation from exposure to T3CP have been reported by gas mask

        Conflicting results have come from epidemiological studies
    relating cancer incidence and mortality to chlorophenol exposure in
    the work place. Associations between soft-tissue sarcoma, malignant
    lymphoma, and nasal and nasopharyngeal cancer, have been shown in some
    epidemiological studies, but not in others. Exposure levels have not
    been accurately determined in these studies, and the conflicting
    results remain unresolved, at present.


    2.1  Identity

        Chlorophenols are organic chemicals formed from phenol
    (1-hydroxybenzene) by substitution in the phenol ring with one or more
    atoms of chlorine. Nineteen congeners are possible, ranging from
    mono-chlorophenols to the fully substituted pentachlorophenol.a
    However, this document does not deal with pentachlorophenol, which has
    been evaluated previously (WHO, 1987b). The chlorophenols
    (particularly trichlorophenols and tetrachlorophenols) are also used
    in the form of sodium or potassium salts. The CAS number, name,
    chemical (molecular) formula, commercial uses, and common synonyms and
    trade names for each chlorophenol congener, are presented in Table 1.
    The general chemical structure for the chlorophenol congeners is shown



    a  The chlorophenol congeners are designated as follows:
       monochlorophenols (MCP); dichlorophenols (DCP); trichlorophenols
       (T3CP); tetrachlorophenols (T4CP); pentachlorophenol (PCP).
       Chlorine substitution is also indicated: 2,4-dichlorophenol
       (2,4-DCP); 2,4,6-trichlorophenol (2,4,6-T3CP), etc.

        Table 1.  Information on the identity of chlorophenol congenersa

    CAS numberb  Common name                Abbreviation   Molecular    Common synonymsc               Common trade
                                                           formula                                     names

    95-57-8      2-monochlorophenol         2-MCP          C6H5ClO      o-chlorophenol;

    108-43-0     3-monochlorophenol         3-MCP          C6H5ClO      m-chlorophenol;

    106-48-9     4-monochlorophenol         4-MCP          C6H5ClO      p-chlorophenol;

    576-24-9     2,3-dichlorophenol         2,3-DCP        C6H4Cl20
    120-83-2     2,4-dichlorophenol         2,4-DCP        C6H4Cl20     NCl-C55345
    583-78-8     2,5-dichlorophenol         2,5-DCP        C6H4Cl20
    87-65-0      2,6-dichlorophenol         2,6-DCP        C6H4Cl20
    95-77-2      3,4-dichlorophenol         3,4.DCP        C6H4Cl20
    591-35-5     3,5-dichlorophenol         3,5-DCP        C6H4Cl20
    15950-66-0   2,3,4-trichlorophenol      2,3,4-T3CP     C6H3Cl30
    933-78-8     2,3,5-trichlorophenol      2,3,5-T3CP     C6H3Cl30
    933-75-5     2,3,6-trichlorophenol      2,3,6-T3CP     C6H3Cl30
    95-95-4      2,4,5-trichlorophenol      2,4,5-T3CP     C6H3Cl30     NCl-C61187                     Collunosol;
                                                                                                       Dowicide 2;
                                                                                                       Dowicide B;
                                                                                                       Preventol 1

    Table 1.  (contd).

    CAS numberb  Common name                Abbreviation   Molecular    Common synonymsc               Common trade
                                                           formula                                     names

    88-06-2      2,4,6-trichlorophenol      2,4,6-T3CP     C6H3Cl30     NCl-C02904                     Dowicide 2; Omal;

    609-19-8     3,4,5-trichlorophenol      3,4,5-T3CP     C6H3Cl30

    4901-51-3    2,3,4,5-tetrachlorophenol  2,3,4,5-T4CP   C6H2Cl40
    58-90-2      2,3,4,6-tetrachlorophenol  2,3,4,6-T4CP   C6H2Cl40     Dowicide 6
    935-95-5     2,3,5,6-tetrachlorophenol  2,3,5,6-T4CP   C6H2Cl40

    a  From: Jones (1981).
    b  Chemical Abstracts Service Registry number.
    c  From: NIOSH (1983) and Verschueren (1983).

    Note:  Owing to the planar nature of the phenol ring, other congeners (e.g., 2,4,5,6-T4CP) are possible, but these are
           identical in structure to the listed congeners.

        Technical grade chlorophenols are heterogeneous mixtures of
    chlorophenol congeners, unreacted precursors, and a variety of dimeric
    microcontaminants. For example, Cochrane et al. (1983) found that
    technical 2,4-DCP contained on average, 92.24% 2,4-DCP, 4.48% 2,6-DCP,
    1.24% 2,4,6-T3CP, 1.09% 2-MCP, and 0.46% 4-MCP.

    Similarly, Levin et al. (1976) examined the composition of 3
    commercial chlorophenol formulations used to control fungi in Swedish
    sawmills and found that Na-2,4,6-T3CP contained approximately 5%
    T4CP, Na-2,3,4,6-T4CP included 5% T3CP and 10% PCP, and technical
    NaPCP contained 5% T4CP.

        Kleinman et al. (1986) determined that commercial Na-T4CP, used
    in the USA, contained 3.1% PCP, 20.7% 2,3,4,6-T4CP, and less than
    0.4% of other chlorophenol congeners. These results are typical,
    showing that roughly 2-12% T4CP congeners occur in technical PCP
    formulations, together with trace quantities of several lower
    chlorophenols (Jones, 1981; Lanouette et al., 1984).

        Contamination of technical chlorophenols varies according to the
    production process used. Because of the elevated reaction temperatures
    used to produce chlorophenols, a number of compounds are present as
    microcontaminants in technical chlorophenol preparations prepared by
    this procedure. These include the polychlorinated dibenzo- p-dioxins
    (PCDDs) polychlorinated dibenzofurans (PCDFs), polychlorinated
    diphenyl ethers, polychlorinated phenoxyphenols, polychlorinated
    benzenes, and polychlorinated biphenyls. Where the alkaline hydrolysis
    of chlorobenzenes is used to manufacture chlorophenols, the technical
    product also contains the unreacted chlorobenzene. Technical
    chlorophenol salts usually also contain an excess of sodium or
    potassium hydroxide.

        While commercial MCP and DCP contain little or no detectable PCDDs
    and PCDFs, presumably because their manufacture does not involve high
    enough temperatures, other chlorophenols may contain up to many mg/kg
    of particular PCDDs, and PCDFs (Firestone et al., 1972; Woolson et
    al., 1972; Levin et al., 1976; Levin & Nilsson, 1977; Rappe et al.,
    1979; Cedar, 1984; Kleinman et al., 1986). Concentrations of PCDDs and
    PCDFs in some American and European chlorophenols are provided in
    Table 2. Tri- and tetrachloro-dibenzoxo-dioxins predominate in T3CP
    formulations, while the hexa, hepta, and octa congeners are the major
    PCDD contaminants in technical T4CP and PCP (Firestone et al., 1972;
    Rappe et al., 1978a). 2,3,7,8-Tetrachloro-dibenzo- p-dioxin
    (2,3,7,8-TCDD) occurs primarily as a contaminant of 2,4,5-T3CP
    (Table 2), though it is present at low g/kg concentrations in T4CP,
    PCP, and NaPCP (Hagenmaier, 1986; Hagenmaier & Brunner, 1987).
    Predioxins (chlorinated phenoxyphenols) may comprise as much as 5% of
    technical CP preparations (Levin et al., 1976; Levin & Nilsson, 1977).

        Most of the data in Table 2 concern chlorophenol formulations from
    the 1970s. As a result of modifications in production chemistry, it is
    likely that the levels of microcontaminants in current formulations
    are somewhat lower. Indeed, all of the 1986 tetrachlorophenol products
    assayed by Agriculture Canada (1987) contained levels of H6CDD that
    were several times lower than those in the earlier reports (Table 2).

    2.2  Physical and Chemical Properties

        Data on some physical and chemical properties of chlorophenols are
    summarized in Table 3. All of the CPs are solids at room temperature,
    except for 2-MCP, which is a liquid. They have strong odours that have
    been described as pungent or medicinal, particularly those of
    2-monochlorophenol (2-MCP) and 2,4-dichlorophenol (2,4-DCP). Taste and
    odour thresholds are so low that Maximum Acceptable Concentrations of
    chlorophenols in drinking-water are based on organoleptic rather than
    toxicological criteria (US EPA, 1980c; WHO, 1984).

        Although the solubility in water of all chlorophenols is poor,
    varying from 2.1  10-1 mol/litre for 2-MCP t o 7.9  10-4 mol/litre
    for 2,3,4,6-T4CP (US EPA 1980c) they readily dissolve in a number of
    organic solvents. In contrast, the sodium or potassium salts of
    chloropenols (most commonly NaT3CP, NaT4CP, and NaPCP) are up to
    four orders of magnitude more soluble in water than the parent
    compounds. The acidity of chlorophenols increases as the number of
    chlorine substitutions increases. Thus, ionization of the higher
    chlorophenols begins at a lower pH than that of the lower
    chlorophenols (pH approximately 3.5 versus 7 for PCP and 2-MCP,
    respectively), with important implications for the interactions
    between pH and chlorophenol sorption (section, or toxicity
    (section 6.1.1). The  n-octanol-water partition coefficient of
    chlorophenols also increases with chlorination, indicating a
    propensity on the part of the higher chlorophenols to bioaccumulate.

    2.3  Conversion Factors

        MCP  1 mg/m3 = 0.190 ppm;   1 ppm = 5.258 mg/m3
        DCP  1 mg/m3 = 0.150 ppm;   1 ppm = 6.667 mg/m3
        T3CP 1 mg/m3 = 0.124 ppm;   1 ppm = 8.076 mg/m3
        T4CP 1 mg/m3 = 0.105 ppm;   1 ppm = 9.488 mg/m3

        Table 2.  Polychlorodibenzo-p-dioxins (PCDDs) and polychtorodibenzofurans (PCDFs) in some American and European
              mono-, di-, tri-, and tetrachlorophenolsa

    Formulation        PCDD                   Concentration           PCDF           Concentration        Year
                                              (mg/kg)                                (mg/kg)              sample

    2-MCP              ND                                             T4CDF          presentb             1967

    2,4-DCP            ND                                             ND                                  1970

    2,6-DCP            ND                                             ND                                  1970d

    Na-2,4,5-T3CP      ND                                             ND                                  1967

    Na-2,4,5-T3CP      2,7-D2CDD                  0.72                ND             1969
                       2,3,7,8-T4CDDc             1.4

    2,4,5-T3CP         1,3,6,8-T4CDD              0.30                ND             1969
                       2,3,7,8-T4CDc              6.2

    2,4,5-T3CP         P5CDD                      1.5                 ND                                  1970

    2,4,5-T3CP         ND                                             T3CDF          presentb             1970

    2,4,5-T3CP         2,3,7,8-T4CDD              0.07                ND                                  1970

    2,4,6-T3CPf        2,3,7-T3CDD               93                   T4CDF           1.5                 1970d
                       1,3,6,8-T4CDD             49                   P5CDF          17.5
                                                                      H6CDF          36
                                                                      H7CDF           4.8

    Table 2.  (contd.)

    Formulation        PCDD                   Concentration           PCDF           Concentration        Year
                                              (mg/kg)                                (mg/kg)              sample

    2,3,4,6-T4CP       H6CDDc                    15                   H6CDF          presentb             1970d
                       H6CDDc                    14                   H7CDF          present
                       H6CDDc                     5.1                 O8CDF
                       O8CDD                      0.17

    2,3,4,6-T4CP       H6CDc                      4.1                T4CDF          < 0.5                 1967
                                                                      P5CDF          10                   (PCDDs);
                                                                      H6CDF          70                   1967d
                                                                      H7CDF          70                   (PCDFs)
                                                                      O8CDF          10

    2,3,4,6-T4CPf      ND                                             T4CDF          presentb             1967d
                                                                      H6CDF          present

    2,3,4,6-T4CPe      T4CDD                      0.7                 T4CDF          ca.10                1970d
                       P5CDD                      5.2                 P5CDF          ca.10
                       H6CDD                      9.5                 H6CDF          ca.60-70
                       H7CDD                      5.6                 H7CDF          ca.60-70
                       O8CDD                      0.7                 O8CDF          ca.10

    2,3,4,6-T4CPe      T4CDD                      0.4                 T4CDF          ca.10                1970d
                       P5CDD                      3.5                 P5CDF          ca.10
                       H6CDD                      5.3                 H6CDF          ca.60-70
                       H7CDD                      2.1                 H7CDF          ca.60-70
                       O8CDD                      0.3                 O8CDF          ca.10

    Table 2.  (contd.)

    Formulation        PCDD                   Concentration           PCDF           Concentration        Year
                                              (mg/kg)                                (mg/kg)              sample

    TCP/PCPg           H6CDD                  1-4 (n = 6)             not reported   1986
                       H7CDD                  40-102 (n = 6)          not reported
                       O8CDD                  27-55 (n = 6)           not reported

    Na-T4CP/PCPg       H6CDD                  N.D.-4 (n = 13)         not reported   1986
                       H7CDD                  10-119 (n = 13)         not reported
                       O8CDD                  5-330 (n = 13)          not reported

    a  Reports of PCDDs from Firestone et al (1972), except where otherwise indicated; quantitative data on
       PCDF concentrations from Rappe et al. (1978a).
    b  Unquantified. See Firestone et al. (1972).
    c  Confirmed by combined gas chromatography-mass spectrometry,
    d  Not reported.
    e  Rappe et al. (1979).
    f  Rappe et al. (1978b).
    g  Agriculture Canada (1987).
    ND:  No congener detected; limit of detection from Firestone et al. (1972) is approximately 0.02 ppm for PCDDs,
         that from Rappe et al. (1978a) is roughly 0.01-0.04 mg/kg (Buser & Bosshardt, 1976).

    Table 3.  Physical and chemical properties of chlorophenols other than pentachlorophenola

    Compound       Relative      Density           Boiling point         Melting point    Flash    Vapour             log
                   molecular                       (C at 760 mm)        (C at 760 mm)   point    pressure           n-octanol/
                   mass                                                                   (C)     (mm)               water
                                                                                                   (temperature)      partition

    2-MCP          128.56        1.2634 (20/4)     174.9                 9                 63.9    1 (12.1 C)        2.15b
    3-MCP          128.56        1.268 (25/4)      214                   33                        1 (44.2 C)        2.50b
    4-MCP          128.56        1.2651 (30/4)     219.75                43.2-43.7        121.1    1 (49.8 C)        2.39b

    2,3-DCP        163                             206                   57-59
    2,4-DCP        163           1.38 (60/7)       210                   45               62       1 (76.5 C)        3.06c
    2,5-DCP        163                             211 (744 mm)          59                                           3.20c
    2,6-DCP        163                             219-220 (740 mm)      68-69                     1 (59.5 C)d
    3,4-DCP        163                             253.5 (767 mm)        68
    3,5-DCP        163                             253 (757 mm)          68

    2,3,4-T3CP     197.45        sublimes          83.5
    2,3,5-T3CP     197.45        248.5-249.5       62
    2,3,6-T3CP     197.45                          272                   58
    2,4,5-T3CP     197.45        1.68 (25/25)e     sublimes              68-70.5                   1 (72 C)          3.72f
                                                                         (275 mm)                  1 (53 C)          3.62c
                                                                                                   1 (76.5 C)

    Table 3.  (contd).

    Compound       Relative      Density           Boiling point         Melting point    Flash    Vapour             log
                   molecular                       (C at 760 mm)        (C at 760 mm)   point    pressure           n-octanol/
                   mass                                                                   (C)     (mm)               water
                                                                                                   (temperature)      partition

    2,4,6-T3CP     197.45        1.49 (75/4)e      246                   69.5             113.9
    3,4,5-T3CP     197.45                          271-277 (746 mm)      101

    2,3,4,5-T4CP   231.98        1.67d             sublimes              116-117
    2,3,4,6-T4CP   231.98        1.6 (60/4)g       150 (15 mm)           70               1 (100 C)                  4.10c
    2,3,5,6-T4CP   231.98                          115

    a  Principal source: Jones (1981).
    b  From: Fujita et al. (1964).
    c  From: Stockdale & Selwyn (1971).
    d  From: US EPA (1980a).
    e  From: Kozak et al. (1979).
    f  From: Leo et al. (1971).
    g  From: Verschueren (1983).


    2.4  Analytical Methods

    2.4.1  Sample collection and storage

        Proper sampling and sample storage are essential prerequisites for
    residue determinations, particularly as picogram or nanogram
    quantities are often encountered in environmental samples. It is,
    therefore, important to minimize contamination, and to collect
    representative samples.

        Chlorophenols in the air have been collected by drawing air
    through an absorbent liquid at a given rate for a given period, using
    absorbents such as potassium carbonate (Dahms & Metzher, 1979) or
    ethylene glycol (Wyllie et al., 1975). If a significant proportion of
    the chlorophenols present is likely to bind to container walls, as
    occurs with water samples, glass containers are preferable to plastic
    ones (Kozak et al., 1979).

        To avoid erroneous determinations, samples should be processed
    immediately or appropriate steps taken to avoid losses through
    degradation. If samples are to be stored for an extended length of
    time after collection, major losses of chlorophenols may occur as a
    result of photodecomposition, oxidation, biodegradation, or
    evaporation (section 4). If it is necessary to store samples, changes
    in residue levels can be reduced by refrigeration or freezing. The
    American Public Health Association (Greenberg et al., 1985) recommends
    preserving waste-water samples containing phenolic compounds by
    acidification with phosphoric acid and treatment with copper sulfate,
    prior to refrigeration.

    2.4.2  Sample preparation and analysis

        The early procedures used to analyse for chlorophenols were
    reviewed by Bevenue & Beckman (1967). Most were colorimetric
    techniques, the most popular being the 4-aminoantipyrine method; none
    of the methods was either very specific or sensitive. They are no
    longer widely used, and are not discussed here. Instead, more
    sophisticated analytical techniques are being increasingly used,
    including thin-layer chromatography (TLC), gas chromatography (GC),
    high-performance liquid chromatography (HPLC), ion exchange
    chromatography, infrared (IR) and ultraviolet (uv) spectroscopy, mass
    spectrometry (MS), and mass fragmentography. Table 4 includes examples
    of the techniques available for the sampling and determination of
    chlorophenols other than pentachlorophenols. An indication of the
    sensitivity of each method is given, when available.

        Table 4.  Analytical methods for chlorophenols other than PCPa

    Matrix     Chlorophenol     Sampling, extraction          Analytical method          Detection limit/      Reference

    Air        T4CP             Bubbler collection;           Derivatization with        0.05 g/m3            Dahms & Metzner
                                absorption in                 acetyl chloride; GC                              (1979)
                                potassium carbonate           analysis, EC detector
                                solution; hexane

    Air        3-MCP            Polyether-type                HPLC analysis, EC          5 ng                  US EPA (1980d)
               4-MCP            polyurethane foam;            detector
               2,4-DCP          Soxhlet extraction
               2,4,5-T3CP       with diethyl ether/
               2,4,6-T3CP       hexane; evaporation;
                                extraction with NaOH,
                                buffered with phosphoric

    Water      2-MCP            Adsorption on                 Florisil column                                  Eichelberger
               2,4-DCP          activated carbon;             with anhydrous                                   et al. (1970)
               2,4,5-T3CP       adsorbates extracted          sodium sulfate for
               2,4,6-T3CP       with chloroform then          clean-up; GC analysis
                                sodium hydroxide
                                followed by ethyl ether

    Table 4.  (cont'd).

    Matrix     Chlorophenol     Sampling, extraction          Analytical method          Detection limit/      Reference

    Surface    2-MCP            Adsorption on                 Form pentafluorobenzyl                           Kawahara (1971)
    water      2,4-DCP          activated carbon;             ether derivatives;
                                adsorbates extracted          GC analysis
                                with chloroform then
                                partitioned into acetone

    Water      2-MCP            Methylene chloride            HPLC analysis,             4.2-12.6 ng;          Realini (1981)
               2,4-DCP          extraction of acidified       UV254 detector             93-97%
               2,4,6-T3CP       sample, followed
                                by ion-pair extraction
                                of basic sample with

    Air        T4CP             Collection in 0.1 N           GC analysis,               0.5 g/m3             Kleinman et al.
                                sodium hydroxide in           EC detector                                      (1986)
                                impingers, acidification,
                                extraction with toluene

    Air        T3CP             Collection in                 Acetylation and            2-5 g/m3             Kauppinen &
               T4CP             toluene in impingers,         extraction with                                  Lindroos (1985)
                                extraction into basic         hexane; GC analysis,
                                borax solution                EC detector

    Table 4.  (cont'd).

    Matrix     Chlorophenol     Sampling, extraction          Analytical method          Detection limit/      Reference

    Water      4-MCP            Adsorb basic sample           GC analysis, Fl            80-102%               Chriswell et al.
               2,4,6-T3CP       on anion exchange             detector; confirmation                           (1975)
                                resin; extraction             by GC-MS
                                of hydrochloric acid
                                and acetone-water
                                eluates with methylene

    Water      T3CP             Adsorb on XAD-4               Derivatization with        T3CP: 1 g/litre,     Woodrow et al.
               T4CP             resin; extract with           diazomethane;              74.8-77.7%;           (1976)
                                acetone, hydrochloric         dissolve in hexane;        T4CP: 0.5 g/litre,
                                acid; concentrate,            HPLC clean-up on           46.7-61.4%;
                                then dilute with              Partisil silica            PCP: 0.5 g/litre,
                                water; partition              column; GC analysis        72.5-85.1%
                                with sodium sulfate,          with EC detector
                                dry over

    Surface    2,4-DCP          Addition of sodium            Extract & derivatize       1-2 ng/litre,         Abrahamsson & Xie
    waste, or  2,6-DCP          phosphate buffer              by adding                  98-105%               (1983)
    drinking-  2,4,6-T3CP       solution, for acid            hexane containing
    water      2,3,4,6-T4CP     waste-water pH                internal standard
                                adjustment to 7               (2,6-dibromophenol)
                                with sodium                   and acetic anhydride
                                hydroxide                     directly to sample;
                                                              GC analysis, EC

    Table 4.  (cont'd).

    Matrix     Chlorophenol     Sampling, extraction          Analytical method          Detection limit/      Reference

    Urine      2,4-DCP          Partitioned into              Purified by TLC; GC                              Kurihara & Nakajima
    (mouse)    2,4,5-T3CP       ethanol or benzene,           analysis thermal                                 (1974)
               2,4,6-T3CP       and water, both               conductivity detector;
                                phases analysed;              confirmation by MS
                                enzyme hydrolysis
                                of water soluble CP

    Urine      T3CP             Benzene extraction            Der. with diazom           1 g/litre,           Edgerton et al.
    (human,    T4CP             from acidified,               ethane; separation on      89.3-97.0%            (1979)
    rat)                        hydrolysed solution           acid alumina column;
                                GC analysis, EC detector;
                                GC-MS confirmation

    Urine      T4CP             Acidic hydrolysis;            LC analysis column:        23 g/litre,          Pekari & Aitio
    (human)                     hexane/isopropanol            Spherisorb ODS;            54.6%                 (1982)
                                extraction;                   mobile phase:
                                evaporation and               methanol +
                                redistillation in             ammonium carbonate;
                                methanol-water                UV254 detector

    Table 4.  (cont'd).

    Matrix     Chlorophenol     Sampling, extraction          Analytical method          Detection limit/      Reference

    Urine      2-MCP            Hydrolyse conjugates          Der. with sodium                                 Hargesheimer & Courts
    (human)    4-MCP            in acidified sample           bicarbonate then                                 (1983)
               2,4-DCP          by boiling; make              acetic anhydride
               2,6-DCP          basic with sodium             extraction methylene
               2,4,5-T3CP       hydroxide extract             chloride; GC analysis,
               2,4,6-T3CP       with methylene                EC and FI detectors;
                                chloride; neutralize,         confirmation by MS
                                dry with sodium

    Blood      3-MCP            Hydrolysis with               HPLC analysis,             5 ng,                 US EPA (1980d)
    (human)    4-MCP            hydrochloric acid             EC detector                80-100%
               2,4-DCP          extraction with hexane
               2,4,5-T3CP       ethyl ether;
                                extraction with sodium
                                hydroxide, buffered
                                with phosphoric acid

    Table 4.  (cont'd).

    Matrix     Chlorophenol     Sampling, extraction          Analytical method          Detection limit/      Reference

    Animal     2,4-DCP          Optional alkaline             Der. to trimethylsilyl     0.02 mg/kg            Clark et al. (1975)
    tissue     2,4,5-T3CP       digestion; acid               ether; GC analysis         (2,4-DCP);
    (sheep                      hydrolysis;                                              0.01 mg/kg, > 95%
    cattle)                     distillation with water;                                 (2,4,5-T3CP)
                                methylene chloride

    Sediment   T4CP             Homogenization; toluene       Derivatization             0.5-25 g/kg,         Butte et al. (1983)
    and clams                   extraction from               pyrolytic ethylation       76.7-98.8%
                                acidified sample              with triethylsulfonium
                                2,4,6-tribromophenol          iodide; GC analysis,
                                as internal standard          EC detector;
                                                              Confirmation by MS

    Fish       2-MCP            Gel permeation                Derivatization with        2-MCP-47%             Stalling et al.
    tissue     2,4-DCP          chromatography to remove      pentafluorobenzyl          2,4-DCP-78%           (1979)
               2,4,6-T3CP       lipids, free fatty            bromide; silica            2,4,6-T3CP-86%
                                acids; acid-base              gel chromatography         PCP-63%
                                extraction                    clean-up; GC analysis,
                                                              EC detector

    Meat and   2,4-DCP          Alkaline digestion;           Derivatization             10 g/kg,             Sackmauerova-Veningerova
    poultry    2,3,4-T3CP       steam distillation of         with methyl iodide;        92-98%                et al. (1981)
    livers     2,4,5-T3CP       acidified sample;             GC analysis;
               2,4,6-T3CP       toluene extraction            EC detector
                                dry sodium sulfate,

    Table 4.  (cont'd).

    Matrix     Chlorophenol     Sampling, extraction          Analytical method          Detection limit/      Reference

    Muscle     2,4-DCP          Blended in                    GC analysis,                                     Sherman et al. (1972)
    (hen)                       hexane-sulfuric acid;         EC detector
                                extraction with
                                NaOH, then hexane

    Liver      2,4-DCP          Ground; dried with            Florisil column                                  Sherman et al. (1972)
    (hen)                       sodium sulfate eluted         for clean-up; GC
                                with hexane;                  analysis, EC detector
                                extraction of eluate
                                with acetonitrile,
                                then hexane; dried
                                with sodium sulfate

    Soil       2-MCP            Steam distillation of         GC analysis, EC            < 0.1 mg/kg           Narang et al. (1983)
               2,4-DCP          acidified sample;             detector                   2-MCP-59%;
               2,4,6-T3CP       extraction with                                          2,4-DCP-64%;
                                toluene dichloromethane                                  2,4,6-T3CP-70%
                                eluted through anhydrous
                                sodium sulfate
                                extraction with

    Table 4.  (cont'd).

    Matrix     Chlorophenol     Sampling, extraction          Analytical method          Detection limit/      Reference

    Wood       2,3,4,6-T4CP     Extraction with diethyl       Elution from TLC           200 mg/kg dust        Levin & Nilsson (1977)
    dust                        ether; evaporation;           with n-hexane;             70%
                                dissolve in acetone           derivatization
                                and TLC (silica gel)          with diazomethane;
                                                              GC with Ni63
                                                              EC detector

    Wood       2,4,6-T3CP       Pumped through                GC analysis, EC                                  Kauppinen & Lindroos
    dust       2,3,4,6-T4CP     membrane filter;              detector                                         (1985)
                                Soxhlet extraction
                                with diethyl ether;
                                evaporate; dissolved
                                in hexane

    a  GC = gas chromatography.
       TLC = thin-layer chromatography.
       HPLC = high-performance liquid chromatography.
       MS = mass spectrometry.
       EC = electron capture detection.
       FID = flame ionization detection.



    3.1  Natural Occurrence

        Some chlorophenols are present in the environment independent of
    man-made input. Dichlorophenols have been detected in a variety of
    organisms (Siuda, 1980). 2,4-Dichlorophenol occurs naturally in a
     Penicillium sp., while 2,6-DCP serves as a sex pheromone for several
    species of tick. A number of related organohalogens are also found in
    flora and fauna (Arsenault, 1976; Siuda, 1980). However, these sources
    cannot account for the significant amounts of chlorophenols,
    particularly the higher chlorinated phenols, found in the environment.

    3.2  Man-made Sources

    3.2.1  Production levels and processes  World production figures

        Reliable data on production levels of chlorophenols other than PCP
    are not readily available. In 1975, the combined global production of
    all chlorophenols approached 200 million kilograms (Table 5). Slightly
    more than half consisted of chlorophenols other than PCP, with
    2,4-DCP, 2,4,5-T3CP, and 2,3,4,6-T4CP predominating. Where
    commercial use data are available, recent figures indicate that
    consumption has declined (IARC, 1986). Chlorophenols are used in
    countries other than those shown in Table 5, but the quantities used
    are not known. Information on PCP production is presented in WHO
    (1987b).  Manufacturing processes

        While most chlorophenols can be produced by several different
    procedures, only a few methods are actually used in commercial
    manufacture (Doedens, 1963; Freiter, 1979). Most chlorophenols are
    made by the direct stepwise chlorination of phenol or lower
    chlorinated phenols at an elevated temperature. The compounds 2-MCP,
    4-MCP, 2,4-DCP, 2,6-DCP, 2,4,6-T3CP, 2,3,4,6-T4CP, and PCP are
    manufactured by this means. The manufacture of T4CP or PCP requires
    the use of a catalyst, such as iodine, aluminium chloride (AlCl3),
    ferric chloride (FeCl3), or antimony chloride (SbCl3). The process
    is not quantitative, with the result that batches of one chlorophenol
    will usually contain substantial amounts of other CPs (section 2.1).

        Table 5.  Production/consumption of chlorophenols other than PCP

    Country    Compound                  Year     Production/           Reference

    Global     total chlorophenols       1975     1.8  108 (P)a        Levin & Nilsson

               non-PCP                   1978     0.98  108 (P)        Ahlborg &
               chlorophenolsb                                           Thunberg

    Canada     total chlorophenols       1976     3.4  106 (C)         Jones (1981)
               non-PCP chlorophenols              1.5  106 (C)b

               total chlorophenols       1981     > 5.266  106 (C)     Jones (1984)
                                         1981     4.000  106 (P)
               non-PCP chlorophenols     1981     > 3.730  106 (C)

               tetrachlorophenol         1981     7.86  105 (C)        Jones (1984)
               and Na-T4CP                        12.44  105 (P)

               Na-T3CP                   1981     3.0  103 (C)         Jones (1984)
                                                  1.0  103 (P)

               2,4-dichlorophenol        1981     3.700  106 (C)       Jones (1984)
                                                  1.850  106 (P)

               total chlorophenols       1984     3.89  106 (S)        Environment
               non-PCP chlorophenols     1984     4.91  105 (S)b       Canada

               tetrachlorophenol         1984     4.9  105 (S)         Environment
               and Na-T4CP                                              Canada

               2,4,5-trichlorophenol     1984     < 1.0  103 (S)       Environment
               and Na-2,4,5-T3CP                                        Canada

    Europe     monochlorophenols                  4.5  106 (P)         Krijgsheld &
                                                                        van der Gen
               2,4-dichlorophenol                 9.1  106 (P)         (1986)

    Table 5. (contd).

    Country    Compound                  Year     Production/           Reference

    United     total chlorophenols       1972     > 1.14  106 (C)d     Ahlborg &
    Kingdom                                                             Thunberg

    USA        total chlorophenols       1976     > 2.421              Buikema et al.
                                                  107 (S,P)c,d          (1979)

               non-PCP chlorophenols     1976     > 1.995              Buikema et al.
                                                   106 (S,P)b           (1979)
               2,4-Dichlorophenol        1976     1.995  106 (S)

    a  P = production, C = consumption, S = sales volume.
    b  By difference, from data presented in reference.
    c  Sales approximate consumption, since most use is domestic (Jones, 1981).
    d  A conservative estimate, derived by adding figures for major chlorophenols.
        Alternatively, some chlorophenols are produced by the alkaline
    hydrolysis of hexachlorobenzene (HCB) or other chlorobenzenes in
    methanol, ethylene glycol, and other solvents. The compounds 2,5-DCP,
    3,4-DCP, 2,4,5-T3CP, 2,3,4,5-T4CP, 2,3,5,6-T4CP, and PCP can be
    synthesized by this type of reaction (Doedens, 1963; Freiter, 1979).

        Both methods may yield contaminants that are themselves potential
    health hazards, specifically PCDDs, PCDFs, and 2-phenoxyphenols
    (section 2.1), especially if optimum reaction conditions are not
    maintained (particularly temperature and pressure) in the production
    of higher chlorophenols. In addition, chlorophenols derived from the
    hydrolysis of chlorobenzenes may include substantial amounts of the
    initial isomer in the final product.

    3.2.2  Uses

        The uses of commercial chlorophenols are summarized in Table 6.
    These compounds are biocides, a property that accounts for many of
    their uses. Chlorophenols, particularly tetra-, and to a lesser
    extent, trichlorophenols, have been used as bactericides, algicides,
    molluscicides, acaricides, fungicities, and mould inhibitors, and for
    less specific uses, such as general antiseptics and disinfectants.
    Chlorophenols are also used as intermediates in the production of
    certain herbicides, dyes, and drugs.

        At present, use patterns are more restricted than is indicated in
    Table 6. For example, revisions to Canadian standards for chlorophenol
    in 1980 resulted in a sharp reduction in use in domestic interiors,
    agriculture, the leather industry, and as slimicides in the pulp and
    paper industries. Both the quantities and patterns of use are even
    more restricted in some countries. For example, in Sweden and Finland,
    chlorophenols are no longer used, or use is severely restricted in the
    wood preservation or pulp and paper industries (Ahlborg & Thunberg,
    1980; Lindroos et al., 1987).

        Most chlorophenols are applied in the form of a chlorophenol-oil
    mixture, but some are dissolved in a "clean" carrier that can be
    recovered, such as methylene chloride (Jones, 1981). In contrast, the
    sodium salts of higher chlorophenols (particularly T3CP, T4CP, and
    PCP) are readily soluble in water.  Wood treatment

        Large quantities of higher chlorophenols are used in wood
    preservation (Table 6). In Canada in 1981, most chlorophenol-treated
    wood was preserved by pressure treatment with pentachlorophenol
    (Table 7). This compound has been evaluated previously (WHO, 1987b),
    and will not be covered here.

        Substantial amounts of the sodium salts of T4CP (ca. 13% of total
    1981 chlorophenol consumption: Table 7), and lesser amounts of NaT3CP
    and NaPCP have been used to protect fresh-cut logs and lumber. These
    compounds, which are readily soluble in water, are used to surface-
    treat lumber by dipping or spraying to protect against sapstain or
    mould. Some plywood mills also use T4CP to reduce decay and mould,
    and insect attack. The preservative is usually added to the glue.  Agriculture

        At one time, chlorophenol-treatment was widely used in
    agriculture, to prevent wood decay in buildings, food containers, and
    horticultural timbers. Recently, such chlorophenol applications have
    been considerably restricted in some countries (section 3.2.2), and as
    a result, the quantities of non-PCP chlorophenols used in agriculture
    are minor (Jones, 1981).

        Table 6.  Principal uses and reactions of selected chlorophenols other than PCPa

    Compound                 Principal uses                 Other uses

    2-chlorophenol           Intermediate for               Polymer intermediate for
                             further chlorination to        fire-retardant varnishes;
                             2,4-dichlorophenol,            cotton fabric treatment
                             2,4,6-trichlorophenol,         to provide rot resistance;
                             and pentachlorophenol          ingredient in coal
    4-chlorophenolb          Intermediate for
                             higher chlorophenols;
                             intermediate dyes,
                             fungicides, and drugs

    2,4-dichlorophenol       Intermediate for               Intermediate for
                             production of 2,4-D and        production of Sesone,
                             other herbicides;              Nitrofen, Nemacide,
                             ingredient of                  Genite-EM-923; raw
                             antiseptics; starting          material for polyester
                             material for higher            films; mothproofing;
                             chlorophenols                  miticide

    2,4,5-trichlorophenol    Intermediate in                Germicides and
                             manufacture of 2,4,5-T         ingredients of
                             and related herbicides;        germicidal soaps
                             fungicide, bactericide,

    2,4,6-trichloropenol     Precursor for higher CPs;
                             germicide, particularly for
                             preservation of wood,
                             leather, glue, and textiles;
                             intermediate in preparation
                             of insecticides and soap

    2,3,4,6-                 Fungicide and bactericide      Preservative for latex
    tetrachlorophenol,       for wood preservation;         and leather; preservative
    and its sodium salt      sodium salt is sapstain        in glue for plywood
                             inhibitor; pesticide

    a  From: US EPA (1979).
    b  From: US EPA (1980c).

        T4CP is an active ingredient in formulations of PCP used as wood
    preservatives for homes, and as an additive to paints and stains
    (Table 6). Sales in Canada for these purposes contribute only a small
    fraction to the total PCP market (Jones, 1981) (Table 7) as a result
    of recent government restrictions on their use (section 3.2.2). T3CP
    is used as a general-purpose home antiseptic and as the active
    ingredient in some throat lozenges. At one time, 4-MCP was found in
    disinfectants for home, farm, dental, hospital, and veterinary uses,
    but has been largely replaced by other chemicals (Exon, 1984).

        Table 7.  Canadian use patterns for chlorophenols and their sodium
              salts in 1981a

    Use                      Product    Consumptionb       % of Total
                                        (kg  103/year)

    Wood preservation        PCP          1536               25.2
    (pressure treatment)

    Wood protection          Na-PCP         32                0.5
    (surface treatment)      Na-T4CP       786               12.9
                             Na-T3CPc        1                0.02

    Intermediates for        2,4-DCPd     3700               60.7
    phenoxy herbicides

    Additives in products    NaPCP          38                0.6
    listed in footnote e     NaT3CPc         2                0.03

    Total                                 6095

    a  From: Jones (1984).
    b  Includes chlorophenols present in exports (13.6% of total
       consumption), principally treated wood products.
    c  Chlorophenols are no longer registered for use in Canada.
    d  2,4-D is no longer produced domestically, though considerable
       quantities continue to be imported.
    e  Adhesives, construction materials, fabrics, fibreboard
       products, finished paper, leather, paper machine felts,
       photographic solutions, pulp and paper process solutions,
       rayon emulsions, rubber, rubber gaskets.  Water treatment

        Information is lacking on the use of non-PCP chlorophenols in
    water-treatment applications (Jones, 1981).  Additives

        Sodium salts of T3CP and T4CP have been used to inhibit
    microbial growth in a diverse array of products (Tables 6 & 7). These
    applications make up only a small fraction of the total consumption of
    chlorophenols (Jones, 1981).  Intermediates in industrial syntheses

        Production of chlorophenols is stepwise and not quantitative,
    hence lower chlorophenols are generally recycled within a reactor
    system, or recycled from other manufacturing processes in the
    production of the higher chlorinated phenols. The lower chlorophenols
    also serve as intermediates in the production of other pesticides
    (Table 6). Large amounts of 2,4-DCP are consumed in the manufacture of
    the phenoxy herbicide 2,4-D (Table 7), and also as a precursor for the
    production of the pesticides Sesone, Nitrofen, Nemacide, and
    Genite-EM-923. 2,4,5-T3CP is used in the manufacture Ronnel(R),
    2,4,5-T, and related herbicides, while 4-MCP is used in the production
    of the germicide 4-chlorophenol- o-cresol. Small amounts of lower
    chlorinated phenols have been used in the manufacture of some dyes and

    3.2.3  Other sources

        Chlorophenols are also generated by human activity via several
    indirect routes. They are formed as by-products of chlorine bleaching
    in paper-mills, and subsequently released into the environment
    (Ahlborg & Thunberg, 1980; Xie et al., 1986) (section The
    chlorination of municipal and industrial wastes, and municipal
    drinking-water can give rise to mono-, di-, and trichlorophenols in
    the g/litre range (NRCC, 1978). At these levels, the taste and odour
    of water may be affected locally, though the chlorophenol
    concentrations are well below those that produce any observable toxic
    effect in test organisms (section 6.1). The incomplete incineration of
    chlorophenol wastes can release substantial quantities of these
    compounds into the environment (section 3.4). The lower chlorinated
    phenols are also formed as a result of the bioconversion of lower
    chlorinated benzenes and related compounds (Ballschmiter & Scholz,
    1980). The contributions of these sources to environmental release or
    human exposures to chlorophenols are generally not well-defined, and
    are not considered in subsequent sections.

    3.3  Waste Disposal

        Waste-waters containing chlorophenols arise from three sources,
    i.e., the manufacture of chlorophenols, the manufacture of compounds
    in which chlorophenols are used as intermediates, and wood-treatment
    facilities. Both manufacturers and regulatory agencies have emphasized
    appropriate process design, in order to minimize the volume of waste
    generated, particularly in the treatment of lumber (Richardson, 1978).

        Information on the handling of chlorophenol-containing wastes in
    Canada is limited. In the past, some industries disposed of
    2,3,4,6-T4CP and PCP-contaminated wastes as raw effluent into deep
    wells, or into lagoons, prior to discharge into the North Saskatchewan
    River (Jones, 1981). However, most Canadian wood-treatment plants
    report that they do not have any discharge and are able to dispose of
    their minimal wastes by incineration, or containment and evaporation
    in lagoons. Data to confirm the adequacy of such treatments are
    generally not collected (Richardson, 1978), but they are probably
    adequate, if applied correctly.

        While waste-water treatment plants have been used in only a few
    large wood-preserving plants and by some chemical manufacturers (US
    EPA, 1979), their use is increasing in response to environmental
    concerns. Such methods and their efficiency have been described (US
    EPA, 1979).

        Usually primary treatment is applied only in instances where the
    chlorophenol in question is dissolved in a carrier oil, when gravity
    separation tanks are used to recover the oil and associated
    chlorophenol for subsequent recycling or waste treatment. A few plants
    also use hay or sand filtration to remove some oil droplets and wood
    particles (Richardson, 1978). Flocculation is not widely used, because
    flocculents have proved ineffective or inconsistent in removing
    chlorophenols (US EPA, 1979).

        Chlorophenols are effectively removed by secondary treatment under
    favourable conditions. Roughly 90% of total phenols were removed from
    waters containing wastes from the manufacture of phenoxy herbicides in
    aerated lagoons (US EPA, 1971) or by trickling filter/activated sludge
    treatments (Mills, 1959). Several laboratory and treatment-plant
    studies have shown that PCP can be degraded by activated sludge (Dust
    & Thompson, 1973; Kirsch & Etzel, 1973; Etzel & Kirsch, 1974; Moos et
    al., 1983; Guthrie et al., 1984; Hickman & Novak, 1984), a fluidized
    bed reactor (Hakulinen & Salkinoja-Salonen, 1982), and a biofilm
    reactor (Salkinoja-Salonen et al., 1984). However, of 14 municipal
    treatment plants surveyed by the US EPA, 8 did not remove any of the
    PCP load, while the remainder were considered to remove PCP (6-87%)
    primarily by adsorption on solids (Hickman & Novak, 1984).

    Furthermore, degradation by microorganisms is sharply reduced, when
    chlorophenol concentrations are excessive (Broecker & Zahn, 1977;
    Reiner et al., 1978; El-Gohary & Nasr, 1984; Salkinoja-Salonen et al.,
    1984). If secondary treatment facilities are to remove chlorophenols
    reliably, they must include acclimated organisms, and chlorophenol
    concentrations must be dilute and fairly stable (Hickman & Novak,
    1984). These considerations suggest that such wastes are best handled
    by a facility designed specifically to treat them, rather than being
    treated at general-purpose sewage-treatment plants.

        Chemical oxidation, using such chemicals as chlorine or potassium
    permanganate, may also be effective in treating
    chlorophenol-contaminated wastes. While chlorination of municipal
    wastes can actually produce mono-, di-, and tri- chlorophenols, they
    are subsequently oxidized together with higher chlorophenols to
    compounds that are less toxic and/or more biodegradable (US EPA, 1979;
    Sithole & Williams, 1986).

        Adsorption of chlorophenols on activated carbon is sometimes used
    as a final clean-up step for waste-waters, though this is feasible
    only when waste treatment is handled in the same plant from start to
    finish. Removal of 2,4-DCP (Aly & Faust, 1964) and PCP (Richardson,
    1978) approaches 100% using this method.

        Incineration has also been used to dispose of chlorophenol wastes,
    but the available information deals mainly with PCP. A controlled air
    incinerator destroyed more than 99.99% of PCP in treated wood at
    combustion temperatures of between 916 and 1032C, and yielded no
    measurable T4CDD or T4CDF in the off-gas (Stretz & Vawuska, 1984).
    However, incinerator temperatures must be high enough and residence
    times long enough to ensure complete combustion. Rappe et al. (1978b)
    demonstrated that burning technical T4CP at low temperatures
    increased the content of PCDDs. Similarly, low-temperature destruction
    in hog-fuel or "wigwam" burners fed chlorophenol-contaminated sawdust
    and wood shavings can lead to the formation of PCDDs and PCDFs (Crosby
    et al., 1981).

    3.4  Losses of Chlorophenols into the Environment

        In the absence of information from other countries, releases of
    chlorophenols into the Canadian environment for 1981 (Jones, 1984) are
    presented in Table 8 by way of an example. Of the 5.27  106 kg of
    chlorophenols consumed in Canada in 1984, 1.37  106 kg (26%) were
    eventually released into the environment. A large proportion (less
    than 28%) of these releases would have been as PCP and NaPCP, but the
    data compiled in the table do not distinguish these from T4CP and

        Table 8. Chlorophenol releases into the Canadian environment in 1981a

             Source                                      Quantity (kg  103/year)

    1. Releases in wastes from production sites
                            emissions                         3
                            effluents                        70
                            solids                            -
                                 sub-total                 > 73

    2. Releases in other wastes
             (a) Industrial
                  (i)  Wood preservation sites
                            liquid                            2
                            solids                            -
                            incineration (hog-fuel)           -
                            landfill                          1 (PCP, T4CP)
                                 sub-total                  > 3

                  (ii) Saw-mill/planer mill
                            liquid                           21
                            solids                            -
                  (ii) Incineration (hog-fuel)              272
                       Pulp mills/landfill                    -
                                 sub-total                 >293 (NaPCP, NaT4CP)

             (b) Agricultural
                       solids (livestock litter)
             (c) Domestic
                       incineration (mun.)

    3. Releases during storage and transport
       (solids and liquids)
             (a) Industrial                                 3.5
             (b) Agricultural                               3.4
             (c) Domestic                                   0.1
                                 sub-total                  7.0

    Table 8. (cont'd).

             Source                                      Quantity (kg  103/year)

    4. Releases in situ from treated products
                            (solids and liquids)
             (a) Industrial                                 618
             (b) Agricultural                               370  (2,4-DCP)
             (c) Domestic                                     1
                                 sub-total                  989
             Grand total                                 > 1365

    a  From: Jones (1984).

        In 1981, a significant amount (ca. 5%) of the total releases of
    chlorophenols in Canada occurred from production sites. Following this
    estimate, production of all chlorophenols ceased in Canada. However,
    this route could be a significant source of chlorophenol contamination
    in countries where they are still manufactured. Releases from plants
    will include a variety of chlorophenols from the manufacture of
    chlorophenols and chlorophenol-derived products. A small proportion of
    these materials reaches the environment after incineration (Table 8),
    but the bulk of the chlorophenols released from production sites in
    Canada is diluted and released as untreated effluent.

        Losses into the environment during the storage and transport of
    chlorophenols are small (Table 8), comprising less than 1% of the
    total production.

        The majority (>70%) of the chlorophenols released into the
    Canadian environment arose from treated products (Table 8). About
    two-thirds of these came from industrial sources, which were not
    identified by Jones (1984). Petrochemical drilling fluids contain
    large amounts of chlorophenols (from 700 to 1400 mg NaPCP/kg), to
    prevent fermentation of polysaccharides, starch, and polymers (Jones,
    1981). Once used, the drilling waste is stored on site, in sumps that
    are often subject to flooding and washing out. In-service treatment
    with wood preservatives, principally PCP and its salts, also results
    in some spillage. Large spills have been responsible for fish kills in
    waters contaminated in this fashion (Jones, 1981). In addition,
    unknown, but presumably large, quantities of PCP and T4CP are leached
    from treated lumber in storage or in service. The remaining third of

    the environmental releases, which Jones (1984) identifies as primarily
    2,4-DCP, is from agricultural sources. Commercial preparations of
    pesticides, particularly 2,4-D, 2,4,5-T, and Lindane, contain
    chlorophenols as contaminants. Furthermore, chlorophenols are among
    the early degradation products of these widely-used chemicals.
    Chlorophenols from these sources contaminate soils treated with the
    pesticides, and runoff from these soils finds its way into adjacent
    water bodies and ground water.

        Much of the remaining input of chlorophenols into the environment
    occurs in the form of industrial wastes. These comprise roughly 22% of
    the total chlorophenol releases, primarily as NaT4CP and NaPCP. Most
    of these are released in liquid wastes from pulp-mills (where they are
    by-products of chlorine bleaching), untreated wastes from sawmills,
    planer mills, and other facilities where they are used in wood
    preservation, and during incineration of contaminated sawdust and wood
    shavings. Losses of other chlorophenols from such commercial uses are
    negligible (Table 8).

        The quantities of chlorophenols lost to the atmosphere by
    volatilization are not known. Nanogram-per-litre quantities of
    chlorophenols have been detected in rainfall and snow (Paasivirta et
    al., 1985), suggesting that significant quantities volatilize or are
    adsorbed on airborne particulates.

        The contributions to the environmental load of chlorophenols from
    municipal and industrial chlorination processes, the metabolism of
    other chlorinated compounds to chlorophenols, and the domestic use of
    such products as cosmetics, drugs, home-care products, stains, wood
    preservatives, and pesticides are not known.


    4.1  Transport and Distribution

    4.1.1  Atmospheric movement

        While chlorophenols are considered to be primarily water and soil
    contaminants, atmospheric movement also occurs. Measurable quantities
    of chlorophenols have been detected in air, rainfall, and snow,
    sometimes far from obvious point sources (Paasivirta et al., 1985)
    (section 5.1.1). Furthermore, considerable quantities of chlorophenols
    are released as part of incinerator emissions. The relative
    contributions of volatilization and adsorption on particulates to
    these atmospheric levels are not known.  Volatilization

        No estimates of the rate of volatilization of chlorophenols in the
    environment have been published. It appears that losses through this
    process are minimal in natural waters. If the half-times for
    volatilization of 2-MCP and 4-MCP from 0.38 cm of still water measured
    by Chiou et al. (1980) are extrapolated to 1 m depth, the estimated
    half-times are 395 h and 3421 h, respectively (Krijgsheld & van der
    Gert, 1986).

        Diffusion, a process related to volatilization, does not
    contribute significantly to the long-range transport of substances in
    either the soil or aquatic habitats, though it is essential in the
    local replacement of materials lost through volatilization or

    4.1.2  Soil movement  Adsorption

        Environmental transport of chlorophenols, particularly in soils,
    can be affected by adsorption on particulates. Such deposition is
    quite variable. Acidic soils bind chlorophenols strongly, while
    adsorption is minimal under alkaline conditions. Chlorophenols also
    adsorb on organic matter, with the result that adsorption is strong in
    organic soils, but low in mineral soils.

        Thus, Aly & Faust (1964) found that large amounts of three types
    of clay were necessary to adsorb small quantities of 2,4-DCP in
    aqueous suspensions, even under extremely acidic conditions
    (pH 3.6-4.8). Seip et al. (1986) compared the migration rates of
    tritiated water and of dilute solutions (12.5-25 g/litre) of 2,4-DCP,
    2,4,6-T3CP, 2,3,4,6-T4CP, and PCP through packed soil columns. All
    of the chlorophenols migrated more slowly than water. Adsorption was

    moderate in a weakly acid inorganic soil and a basic soil with a
    higher organic content, while no chlorophenols were detected in the
    eluate from a soil with both a low pH and a high content of organic
    matter. In studies by Choi & Aomine (1972, 1974), strongly acidic
    soils adsorbed PCP, while weakly acidic or neutral soils did not
    adsorb it at all. Moreover, soils with a high organic content adsorbed
    PCP strongly, regardless of their pH, while hydrogen peroxide
    digestion of organic matter reduced apparent adsorption (Choi &
    Aomine, 1974). Miller & Faust (1973) confirmed that sorption of a
    number of phenolic compounds on organo-clay was pH-dependent.

        It is difficult to assess the impact of adsorption on chlorophenol
    transport in the environment from the results of the preceding
    studies. Chlorophenol dynamics observed by Seip et al. (1986) suggest
    that chlorophenols bound to soils are continually turned over, and
    that binding sites may be saturated under the appropriate conditions,
    leading to increased mobility and a decreased residence time of
    chlorophenols in the soil body.  Leaching

        In instances when adsorption is minimal, leaching will be an
    important means of chlorophenol transport in the soil. Most
    chlorophenols should be carried into ground- and surface-waters from
    soils that are neutral or alkaline or have a low organic content, or
    through which material can percolate rapidly. No information has been
    found on the leaching of the lower chlorophenols, but Kuwatsuka (1972)
    noted that much of the PCP applied to flooded rice paddies was carried
    through the soil in solution, and it has been reported by Jones (1981)
    that Na-PCP leaches readily from soils.

    4.1.3  Transport in aquatic environments

        While a large fraction of the chlorophenols entering waters is
    probably degraded  in situ (section 4.2), they are nonetheless
    moderately soluble and fairly persistent, and so can be transported
    considerable distances by water. For example, Fox & Joshi (1984)
    detected elevated levels of T4CP and PCP in the surface waters of the
    Bay of Quinte, Lake Ontario, as far away as 82 km from the
    wood-preserving plant where they originated.

        Chlorophenols that are not degraded are concentrated in the
    sediments, perhaps through adsorption on sediment particulates.
    Schellenberg et al. (1984) determined that sorption of chlorophenols
    on natural sediments and aquifer materials was a combined function of
    the pH, the organic carbon content of the potential sorbent, and the
    partition coefficients (known also as soil adsorption coefficients).
    Adsorption was quite strong on non-mineral sediments. Xie et al.
    (1986) observed that the disappearance of chlorophenolic compounds

    discharged from a sulfate pulp-mill was related to the partition
    coefficients of the compounds, and that sediment concentrations were
    quite high near to their source (section, suggesting that
    adsorption strongly influenced the transport of chlorophenolic
    compounds. It was reported by Eder & Weber (1980) that the
    concentration factor (relative to water) of chlorophenols in the
    sediments (38- to 680-fold) and suspended solids (6.3- to 240-fold) of
    the Weser estuary was inversely related to the degree of ionization of
    the chlorophenol. In contrast, Kuiper & Hantsveit (1984) reported that
    both the water and the sediment on the bottom of marine enclosures
    contained similar levels of 4-MCP and 2,4-DCP; this discrepancy is not
    obviously attributable to differences in system pH, or the nature of
    the particulates.

    4.2  Degradation and Bioaccumulation

    4.2.1  Degradation

        As yet, there are few studies addressing the persistence of
    chlorophenols in the environment.  Abiotic degradation

    (a) Photodecomposition

        Many, if not all, chlorophenol isomers are degraded to some extent
    by exposure to ultraviolet radiation (UVR). The breakdown most often
    involves an oxidation reaction that dechlorinates the molecule (Boule
    et al., 1982), though a variety of reactions have been described.

        2,4-DCP in aqueous solution was decomposed in a matter of minutes
    by irradiation from a UV lamp (Aly & Faust, 1964; Crosby & Tutass,
    1966; Nakagawa & Crosby, 1974). The major pathway involved the
    degradation of 2,4-dichlorophenol to 4-chlorocatechol, which in turn
    produced 1,2,4-benzenetriol, and finally a mixture of polyquinoid
    humic acids (Crosby & Tutass, 1966). A similar sequential degradation
    was reported for 2,4,5-T3CP (Crosby & Wong, 1973). Freitag et al.
    (1982) reported that 65.8% of 14C-2,4,6-T3CP on silica gel was
    degraded after 17 h of UVR exposure. No organic by-products were
    detected, most radioactivity being recovered as carbon dioxide.

        The breakdown of chlorophenols is markedly affected by the number
    and position of chlorine substituents on the molecule. Under UVR,
    2,4-DCP degrades to diameric products (Crosby & Tutass, 1966), while
    2,5-DCP degrades to 4-resorcinol (Crosby & Wong, 1973). Omura &
    Matsuura (1971) found that alkaline solutions of monochlorophenols
    degraded as follows: 2-MCP (82.5% lost in 5 h at 40C) to a complex

    mixture with much resinous material, 3-MCP (70%) to resorcinol, and
    4-MCP (55%) to hydroquinone, phenol, and three diphenyls. Aqueous
    solutions of the three monochlorophenol isomers yielded similarly
    varied products in studies by Boule et al. (1982). In later work,
    Boule et al. (1984) determined that among the dichlorophenol
    congeners, substitution at the ortho and meta positions made the
    chemical more reactive than para substitution.

        Only one study has been reported on whether photolysis
    significantly reduces concentrations of chlorophenols other than PCP
     in situ. Hwang et al. (1986) concluded that photolysis was the
    principal degradative pathway (half-life of 3 h or less) for 2,4-DCP,
    2,4,5-T3CP, and PCP, but not 4-MCP, in estuarine surface waters
    (though they noted that mineralization by other mechanisms was
    substantially photo-inhibited under the experimental conditions). Fox
    & Joshi (1984) observed an increase in the ratio of T4CP/PCP in
    surface waters with increasing distance from a wood-preserving plant
    discharge, suggesting that substantial photolysis of PCP occurred, but
    noted that the concentrations were remarkably stable, once the
    chlorophenols were incorporated into the sediments.

    (b) Chemical degradation

        There is one report that indicates that chlorophenols may be
    degraded in the environment by chemical processes. Baker & Mayfield
    (1980) observed losses of 2-MCP, 4-MCP, and 2,4-DCP from sterile
    washed silica sand, sterile aerobic soils, non-sterile anaerobic
    soils, and sterile anaerobic soils. Microbial contamination,
    photolysis, and volatilization were eliminated as causes. The authors
    suggested that the chlorophenols were auto-oxidized, or broken down at
    catalytic sites, but did not eliminate polymerization as a means of
    loss. A number of other research workers, using a wide range of
    chlorophenols, have not detected such abiotic losses (Alexander &
    Aleem, 1961; Aly & Faust, 1964; Tabak et al., 1964; Boyd & Shelton,
    1984).  Degradation by microorganisms

        Although chlorophenols are quite toxic for microorganisms in
    general, they are nonetheless readily metabolized by a large number
    that occur in soils, natural waters, sediments, and sewage sludges.
    This decomposition is often quite rapid, i.e., completed in a matter
    of hours or days. For instance, of 206 isolates from a petroleum waste
    lagoon, 46% were able to degrade chlorophenols as a sole source of
    carbon after acclimation to the particular chlorophenol (Tabak et al.,
    1964). Up to 95% of the added 3-MCP and 4-MCP (initially 150 and
    300 mg/litre respectively) was consumed in 3-6 days, while the same
    amount of 2,4-DCP (200 mg/litre) and 2,4,6-T3CP (initially
    300 mg/litre) disappeared in 7-10 days. No breakdown of 2,6-DCP was
    observed. Similarly, in batch cultures enriched with 50 mg
    chlorophenol/litre and inoculated with soil, 2-MCP, 4-MCP, 2,4-DCP,

    and 2,4,6-T3CP were readily biodegraded and were often removed
    completely in less than 10 days, while 2,6-DCP was only metabolized in
    some studies; 3-MCP, 2,5-DCP, 2,3-DCP, 3,4-DCP, 3,5-DCP, 2,4,5-T3CP,
    2,3,4,6-T4CP and PCP were refractory (Alexander & Aleera, 1961).
    Using an acclimated, activated sludge derived from soil, Ingols et al.
    (1966) observed complete ring degradation of the following compounds
    at 100 mg/litre: 2-MCP in 3 days, 3-MCP in 2 days, 4-MCP in 3 days,
    2,4-DCP in 5 days, and 2,4,6-T3CP in 3 days. As much as 52% of
    2,5-DCP disappeared in 4 days. No decomposition of sodium
    pentachlorophenate occurred. More recently, aerobic microorganisms in
    clay loam soils were able to degrade most of the 2-MCP, 4-MCP,
    2,4-DCP, 2,6-DCP, or 2,4,6-T3CP present (100 mg/kg) within a few days
    without a lag phase (Baker & Mayfield, 1980). More than 70% of added
    3-MCP, 3,4-DCP, 2,4,5-T3CP, and PCP disappeared within 80-100 days,
    while 3,4,5-T3CP and 2,3,4,5-T4CP levels were little changed after
    160 days.

        The results of many other studies have confirmed that most
    chlorophenols can be metabolized by certain microorganisms in water
    (Aly & Faust, 1964; Lee & Ryan, 1979; Baker et al., 1980;
    Blades-Fillmore et al., 1982; Hwang et al., 1986), sediment (Lee &
    Ryan, 1979; Baker et al., 1980), soil (Walker, 1954; Loos et al.,
    1967; Spokes & Walker, 1974; Baker et al., 1980; Pal et al., 1980),
    and activated sludge (Baird et al., 1974; Pitter, 1976; Pal et al.,
    1980; Boyd & Shelton, 1984).

        While bacteria are most frequently studied as the agents
    responsible for chlorophenol biotransformation, they are not alone in
    this capability. Fungi on wood shavings, used as litter for broiler
    chickens, converted 2,3,4,6-T4CP to 2,3,4,6-tetrachloroanisole,
    leading to a musty taint in the chicken flesh (Curtis et al, 1972; Gee
    & Peel, 1974). The genera  Aspergillus and  Penicillium readily
    degrade chlorophenols. Walker (1973) determined that a yeast isolated
    from soil and grown on phenol could metabolize 2-MCP, 3-MCP, 4-MCP,
    and 2,4-DCP, but not 2,6-DCP.

        The relative rate of degradation of chlorophenols generally
    decreases as the number of chlorine atoms on the phenolic ring
    increases (Alexander & Aleem, 1961; Tabak et al., 1964; Ingols et al.,
    1966; Baker & Mayfield, 1980). However, it is possible to obtain the
    reverse result with organisms able to use PCP as the sole carbon
    source: the KC3 bacterium studied by Chu & Kirsch (1973) grew on
    2,3,4,6-T4CP and 2,4,6-T3CP, but metabolized the dichlorophenois
    poorly; the monochlorophenols were not metabolized at all. Rates of
    biodegradation are further affected by the relative position of the
    chlorine atoms on the phenolic ring. Compounds with a chlorine in the
    meta position are generally more stable than those without (Alexander
    & Aleera, 1961; Chu & Kirsch, 1973; Etzel & Kirsch, 1974; Baker &
    Mayfield, 1980). The chlorophenolic products of PCP degradation in
    soils  in vitro support this hypothesis (Ide et al., 1972).

        Microorganisms that have been previously exposed to a compound are
    usually able to metabolize it immediately when re-exposed, and at a
    faster rate than unexposed organisms (Walker, 1954; Alexander &
    Aleera, 1961; Tyler & Finn, 1974; Pal et al., 1980; Blades-Fillmore et
    al., 1982), presumably because exposure induces the enzymes necessary
    to metabolize the chlorophenol. Microorganisms not previously
    acclimated often exhibit a lag time of as much as several days before
    they begin to degrade the compound (Bollag et al., 1968; Spokes &
    Walker, 1974; Lee & Ryan, 1979; de Kreuk & Hantsveit, 1981).
    Similarly, prior exposure to a structurally related compound can
    facilitate the metabolism of chlorophenols, indicating that the
    enzymes induced by the original compound are somewhat nonspecific. As
    noted earlier, PCP-adapted microorganisms utilize T3CPs and T4CPs
    readily (Chu & Kirsch, 1973), while bacteria raised on phenol, lower
    chlorophenols, or phenoxyacetic acids are able to metabolize various
    other lower chlorophenols (Tabak et al., 1964; Loos et al., 1967;
    Walker, 1973; Spokes & Walker, 1974; Boyd & Shelton, 1984).

        Research workers have found little or no anaerobic biodegradation
    of chlorophenols (Gee & Peel, 1974; Lee & Ryan, 1979; Baker &
    Mayfield, 1980; Horowitz et al., 1982; Pignatello et al., 1986). The
    persistence of PCP and T4CP in sediment cores, several decades old,
    which were presumably anaerobic, supports these findings (Fox & Joshi,
    1984). However, under the right conditions, anaerobic metabolism can
    be substantial: acclimated anaerobic sludge from a municipal sewage
    plant degraded 25 mg monochlorophenols/litre in a few days (Boyd &
    Shelton, 1984).

        Only a few studies can be used to compare chlorophenol
    biodegradation between habitats under conditions that may be readily
    extrapolated to a natural situation. The  in vitro aerobic breakdown
    of 2-MCP, 4-MCP, and 2,4-DCP (100 mg/kg) has been studied in clay loam
    soil (Baker & Mayfield, 1980; Baker et al., 1980), freshwater
    sediments (Baker et al., 1980), and streams (Baker et al., 1980) at
    temperatures ranging from 0 to 23C. In soil incubated at 23C, at
    least 70% of added 2-MCP disappeared in 0.5-1.0 days, 4-MCP in 1-2
    days, and 2,4-DCP in 7-20 days (Baker & Mayfield, 1980). In contrast,
    decomposition in sediments was slower: at 20C, 2-MCP disappeared in
    10-15 days, 4-MCP, in 30 days, and 73% of 2,4-DCP, in 15-30 days
    (Baker et al., 1980). Virtually no biological degradation of
    monochlorophenols occurred in the stream water at 20C, but 2,4-DCP
    levels were reduced by 74% in 10 days at 20C. These differences may
    be related to the favourable conditions for microorganisms that exist
    in soils and sediments, in which levels of organic matter and
    particulate surface area are high. Addition of sterile sediments or
    several inert substances enhanced the degradation of 50 g
    2,4,6-T3CP/litre in river water (Blades-Fillmore et al., 1982).

        In other reports, chlorophenol degradation in water has proceeded
    more rapidly (eliminated in 1-3 weeks) (de Kreuk & Hantsveit, 1981;
    Blades-Fillmore et al., 1982; Hwang et al., 1986). It is possible that
    chlorophenols are generally degraded faster in soils and aerobic
    sediments than in water but, wherever a suitable combination of
    microflora and physical and chemical factors occurs, these general
    differences can be overridden.

        In summary, a number of microorganisms from a variety of habitats
    can readily degrade chlorophenols, especially if previous exposure to
    these compounds has induced the enzymes necessary for their
    metabolism. This process is slowest with exposure to the higher
    chlorophenols, particularly those that are meta-substituted. The
    results of incubation studies in the laboratory suggest that
    biodegradation is most rapid in aerobic soils and sediments, and is
    reduced in anaerobic or nutrient-poor habitats.

    4.2.2  Bioaccumulation

        A number of field and laboratory studies have yielded information
    on the bioaccumulation of the chlorophenols. Most of these have
    involved aquatic organisms. Although organisms ranging from bacteria
    to fish generally contain higher levels of chlorophenol residues than
    the environment at large, the concentrations are not large compared
    with those of some other chemicals. Most bioconcentration factors
    (BCFs) fall between 1  102 and 1  103 (Table 9), and substantial
    biomagnification is not evident. Ernst & Weber (1978) and Ernst (1979)
    suggested that  Lanice conchilega displayed exceptionally high BCFs
    because of an unusual halogen metabolism (detectable levels of
    bromophenols were noted, unlike the other invertebrates studied).

        The results of most of the studies in which a range of
    chlorophenols has been surveyed have indicated that bioconcentration
    is a positive function of chlorine number (Kobayashi et al., 1979;
    Hattula et al., 1981b). The higher BCF with increasing chlorine
    substitution most likely results from the high partition coefficient
    or the lower dissociation constant. Other experimental conditions,
    such as length of exposure and exposure concentration, may also
    contribute to the substantial range of BCF values shown in Table 9.

        Clearance rates of chlorophenols from biota are rapid, indicating
    that the bioaccumulation observed in field studies is the result of
    long-term exposure rather than persistence. Landner et al. (1977)
    reported that 2,4,6-T3CP was eliminated from rainbow trout livers,
    three weeks after dosing was discontinued. Similarly, 84-92% of
    2,4,5-T3CP was lost from fathead minnows in the first day after
    exposure (Call et al., 1980), and the half-life for 2-MCP in bluegills
    was less than 1 day (Barrows et al., 1980).

    4.3  Effects of Other Physical, Chemical, or Biological Factors

    4.3.1  pH

        One of the major factors affecting the transport, breakdown, and
    toxicity (section 6) of chlorophenols is pH. Because chlorophenols are
    weak acids in aqueous solution, they exist primarily in the molecular
    form under acidic conditions, while the anion predominates at neutral
    or basic pH. Since the molecular and ionic forms of chlorophenols
    react differently, pH affects a variety of processes that in turn
    influence chlorophenol dynamics. Ionization is further affected by the
    degree of chlorine saturation of the chlorophenol; in general, higher
    chlorophenols are increasingly acid. Throughout the pH range
    characterizing physiological and environmental situations,
    monochlorophenols are present mainly in their molecular form while,
    above pH 3.5, PCP is primarily dissociated. No information on the
    interaction of pH and evaporation of lower chlorophenols was
    available. In their studies on PCP volatilization, Kloppfer et al.
    (1982) determined that the half-life for PCP disappearance, through
    volatilization from their apparatus, was 167 h at pH 3.3 and 3120 h at
    pH 6. No evaporation was detected at pH8.

        Similarly, pH influences particulate sorption phenomena through
    changes in the molecular form of the chlorophenol. As was discussed in
    section 4.2, adsorption on soils, sediments, and suspended solids is
    inversely related to pH.

        The rate of the photolysis of chlorophenols is also altered by pH.
    Aly & Faust (1964) determined that the breakdown of 2,4-DCP in aqueous
    solution was extremely rapid under alkaline conditions and relatively
    slow under acidic conditions: approximate half-lives for photolysis at
    pH values of 4, 7, and 9 were 34, 15, and 2 min, respectively.
    Similarly, Omura & Matsuura (1971) reported that the rate of
    photolysis of 4-MCP increased as the pH increased. In addition, pH
    exerts an influence on the biodegradation of chlorophenols. An
    activated sludge culture grew well on 2-MCP and 3-MCP at neutral, but
    not at alkaline pH (Ingols et al., 1966). Tyler & Finn (1974)
    determined that a  Pseudomonas species grew best on 2,4-DCP at a pH
    range of 7.1-7.8.

        Table 9.  Bioconcentration estimates for various chlorophenols from field and laboratory data

    Organism          Compound       Length of     Bioconcentration    Remarks                               Reference
                                     exposure      factora


    Oedogonium        2,4,6-T3CP     36                 1720           Aquatic microcosm, 0.5 g/litre,      Virtanen & Hattula
                                                                       long-term exposure                    (1982)
    Echinodorus       2,4,6-T3CP     36                 1000           Aquatic microcosm, 0.5 g/litre,      Virtanen & Hattula
                                                                       long-term exposure                    (1982)
    Elodea            2,4,6-T3CP     36                 4460           Aquatic microcosm, 0.5 g/litre,      Virtanen & Hattula
                                                                       long-term exposure                    (1982)

    Chlorella         2,4,6-T3CP     1                    51           50 g/litre screening test,           Freitag et al.
    fusca var.                                                         as 14C                                (1982)
    vacuolate         2,4,6-T3CP     1                   580           49 g/litre screening test,           Korte et al.
                                                                       as 14C                                (1978)

    Lymnae            2,4,6-T3CP     36                 3020           Aquatic microcosm, 0.5 g/litre       Virtanen & Hattula
    (adult)                                                            long-term exposure                    (1982)

    Lanice            2,4,5-T3CP     indefinite      24 088b           Field data                            Ernst & Weber
    conchilega        2,4,6-T3CP     indefinite      20 269b           Field data                            (1978)
                      2,3,4,S-T4CP   indefinite      17 625b           Field data
                      2,3,4,6 +
                      2,3,S,6-T4CP   indefinite      11 163b           Field data

    Table 9. (cont'd).

    Organism          Compound       Length of     Bioconcentration    Remarks                               Reference
                                     exposure      factora

    Invertebrates (contd).

    Mytilus edulis    2,3,4,6-T4CP   indefinite        45-60           Field data, receiving waters          Folke et al.
                                                                       for dump leachate                     (1984)


    Roach             2,3,4,6-T4CP   indefinite          200           Field data, pulp-mill inputs          Paasivirta et al.
    (Rutilus)                                                                                                (1985)

    Pike              2,3,4,6-T4CP   indefinite          150           Field data, pulp-mill inputs          Paasivirta et al.
    (Esox lucius)                                                                                            (1985)

    Trout (Salmo      2,4-DCP        1                    10           1.7 mg/litre (LC50)                   Hattula et al.
    trutta)           2,3,5-T3CP     1                    12           0.8 mg/litre (LC50)                   (1981b)
                      2,3,4,6-T4CP   1                   450           0.5 mg/litre (LC50)

    Poecilia young    2,4,6-T3CP     36                1 020           Aquatic microcosm, 0.5 g/litre       Virtanen & Hattula
    female            2,4,6-T3CP     36               12 180           long-term exposure                    (1982)
    male              2,4,6-T3CP     36                7 000

    Fathead           2,4,5-T3CP     28                 1900           Aquatic microcosm, 4.8 mg/litre,      Call et al. (1980)
    minnow            2,4,5-T3CP     28                 1800           single addition, 49.3 g/litre
    (Pimephales                                                        as 14C

    Table 9. (cont'd).

    Organism          Compound       Length of     Bioconcentration    Remarks                               Reference
                                     exposure      factora

    Sunfish           2,3,5,6-T4CP   indefinite                        Muscle/field data, Mississippi        Pierce & Victor
                                                                       lake/spill in December, n = 2         (1978)
                                     6 Januaryd           79           Muscle/spill in December, n = 2
                                     27 Aprild            21
                      2,3,5,6-T4CP   indefinite                        Liver/spill in December, n = 1        Pierce & Victor
                                     6 Januaryd          962           Liver/spill in December, n = 2        (1978)
                                     27 April             72

    Bluegill          2-MCP          28                  214           Continuous-flow aquarium,             Barrows et al.
    (Lepomis                                                           2-MCP at 9.18 l&g/litre,              (1980)
    macrochirus)                                                       as 14C

    Bass              2,3,5,6-T4CP   indefinite                        Muscle/field data, Mississippi        Pierce & Victor
                                                                       lake                                  (1978)
                                     6 Januaryd          218           Spill in December, n = 2
                                     27 Aprild          4962           Muscle, n = 2

    Catfish           2,3,5,6-T4CP   indefinited                       Muscle, n = 1
                                     6 Januaryd          222           Muscle, n = 2
                                     27 Aprild            53
                      2,3,5,6-T4CP   indefinited                       Liver, n = 1
                                     6 Januaryd         8608           Liver, n = 2
                                     27 April           1005

    Table 9. (cont'd).

    Organism          Compound       Length of     Bioconcentration    Remarks                               Reference
                                     exposure      factora

    Fish (contd.)

    Goldfish          2-MCP          25h                   6.4         Static lab. assay, 16 mg/litrec       Kobayashi et al.
                      4-MCP          25h                  10.1         Static lab. assay, 9 mg/litrec        (1979)
                      2,4-DCP        25h                  34           Static lab. assay, 7.8 mg/litrec
                      2 4 5-T3CP     25h                  62           Static lab. assay, 1.7 mg/litrec
                      2,4,6-T3CP     25h                  20           Static lab. assay, 10.0 mg/litrec
                      2,3,4,6-T4CP   25h                  93           Static lab. assay, 0.75 mg/litrec

    Golden orfes      2,4,6-T3CP     3                   310           50 g/litre, screening test           Freitag et al.
    (Leuciscus idus                                                                                          (1982)

    Golden orfes      2,4,6-T3CP     3                   250           30 g/litre, screening test           Korte et al.
    (Leuciscus idus                                                                                          (1978)

    a  Ratio of concentration in organism or tissue:water.
    b  Based on bioconcentration relative to PCP.
    c  Concentrations near LC50 values, but still sublethal.
    d  Sampling date.


    4.3.2  Lack of oxygen

        In general, higher chlorinated phenols are persistent in anaerobic
    environments, because of the low microbial degradation of
    chlorophenols under such conditions. (section

    4.3.3  Inorganic nutrients

        Inorganic nutrients may restrict the rate of chlorophenol
    biodegradation where a shortage of nutrients limits microbial
    activity. Striking seasonal variations noted in the rate of 4-MCP
    degradation in natural sea water incubated in the laboratory (de Kreuk
    & Hantsveit, 1981) were not related to microbial biomass, but
    paralleled the levels of phosphate and nitrate in the samples.
     In vitro addition of nutrients to the sea water stimulated
    biodegradation. Similar results were reported by Kuiper & Hantsveit

    4.3.4  Organic matter

        Like inorganic nutrients, levels of organic matter can influence
    the microbial breakdown of chlorophenols through the control of
    microbial biomass and activity. For example, while chlorophenol
    decomposition was apparent in most soils studied (section, it
    was virtually absent from those containing little or no organic matter
    (Kuwatsuka, 1972). Similarly, low heterotrophic activity, determined
    by the low concentrations of organic substances in water (typically
    mg/kg) relative to those found in soils or sediments (g/kg), may
    account for differences observed in chlorophenol biodegradation
    between these environmental compartments (section Organic
    matter bound to the surface of the soil or sediment particulates may
    also absorb chlorophenols and thereby affect their transport (sections, 4.1.3).

    4.3.5  Temperature

        Volatilization is a direct function of temperature. In their
    studies of PCP evaporation, Kloppfer et al. (1982) determined that the
    half-life for volatilization of PCP was 653 h at 23C, 328 h at 30C,
    and 211 h at 40C. Photolysis can also be temperature-dependent. Omura
    & Matsuura (1971) found that higher solution temperatures increased
    the photodecomposition of 4-MCP. The microbial breakdown of lower
    chlorophenols as a function of temperature was investigated in water,
    soil, and sediment by Baker et al. (1980). As expected, biodegradation
    was higher at 20C or 4C than at 0C. However, high temperatures also
    limit the microbial decomposition of chlorophenols; Tyler & Finn
    (1974) found that growth of  Pseudomonas on 2,4-DCP fell off sharply
    above 25C.

        Under some conditions, exposure of chlorophenols to elevated
    temperatures, such as those used in heating and burning, can lead to
    the formation of chlorinated dibenzo- p-dioxins (PCDDs) and
    dibenzofurans (PCDFs) (Rappe et al., 1978b). Many PCDDs and PCDFs are
    extremely persistent in the environment and are toxic for living
    systems (WHO, in press).

    4.4  Persistence

        As a consequence of chlorophenol decomposition through photolysis,
    biodegradation, and perhaps chemical catalysis, virtually all
    chlorophenol compounds will be eliminated from most environments.
    Some, notably PCP and the lower chlorophenols with a chlorine in the
    meta position, will persist for a longer time than others, but even
    these should eventually be broken down, wherever suitable light
    exposure or microorganisms occur.

        No information is available on the persistence of chlorophenols in
    air. Photodecomposition may be an important removal mechanism,
    particularly for the higher chlorophenols (Callahan et al., 1979).

        The long-term persistence of chlorophenol isomers is only expected
    where there is a lack of degradative activity and/or outward
    transport, allowing them to accumulate, as is illustrated by the range
    of residence times for chlorophenols in aquatic environments.
    Substantial quantities of chlorophenols were eliminated from  in situ
    marine pelagic enclosures (4-MCP and 2,4-DCP) (Kuiper & Hansveit,
    1984) and from fresh waters  in vitro: 2-MCP and 4-MCP (Ettinger &
    Ruchhoft 1950; 2,4-DCP (Aly & Faust, 1964); 2,4,6-T3CP and PCP
    (Schauerte et al., 1982; Sugiara et al., 1984) in roughly 1-3 weeks.
    In contrast, it has been shown that T4CP and PCP in sediments, where
    photolysis and apparently biodegradation are minimal, may persist for
    years (Pierce & Victor, 1978; DeLaune et al., 1983; Fox & Joshi,

        A similar range of persistences has been reported for soils. Most
    of 2-MCP and 4-MCP was removed by microorganisms in soil after 10 and
    20 days, respectively (Walker, 1954). Virtually all of 2,3,4,5-,
    2,3,4,6-, and 2,3,5,6-T4CP (100 mg/kg dry soil) disappeared from
    paddy soils after 4 weeks of incubation  in vitro (Ide et al., 1972).
    Concentrations of trichlorophenols and tetrachlorophenols derived from
    PCP degradation  in vitro were in turn, substantially reduced after
    many days (Kuwatsuka & Igarashi, 1975). The disappearance of at least
    90% of added PCP from soils  in vitro took from 21 to 205 days,
    proceeding most rapidly in soils with a moderate to high organic
    content and acclimated microorganisms (Kozak et al., 1979).

        Most studies of chlorophenol metabolism have only monitored the
    disappearance of the parent compound, but a few others have indicated
    that subsequent metabolism may completely mineralize CPs. Thus,
    labelled 4-MCP, 2,4-DCP, and 2,4,5-T3CP were converted to 14CO2 in
    the  in vitro incubation of estuarine waters and sediments (Lee &
    Ryan, 1979; Hwang et al., 1986). About one half of the radioactivity
    added to aerobic artificial streams as 14C-PCP was recovered as
    carbon dioxide after 21 days (Pignatello et al., 1983). Pure cultures
    and activated sludges may also mineralize chlorophenols to carbon
    dioxide (Teidje & Alexander, 1969; Duxbury et al., 1970; Chu & Kirsch,
    1973; Moos et al., 1983). Methane may be produced under anaerobic
    conditions (Boyd & Shelton, 1984), but more often little or no
    mineralization occurs in anaerobic sediments and sludges (Lee & Ryan,
    1979; Horowitz et al., 1982; Pignatello et al., 1983).

        In most instances, aerobic metabolism involves dechlorination and
    hydroxylation, which are usually followed by cleavage of the phenol
    ring at the ortho position and subsequent complete degradation. The
    products of ring cleavage at the meta position are more resistant to
    degradation and tend to accumulate in the medium. Reductive
    dechlorination is an initial step towards complete mineralization
    under anaerobic conditions (Krijgsheld & van der Gen, 1986).


    5.1  Environmental Levels

        A substantial amount of research has been carried out on the
    concentration of pentachlorophenol in the environment; however,
    relatively few studies have been concerned with the determination of
    the levels of other chlorophenols. Nonetheless, enough information is
    available to make a preliminary survey of the residues of these
    chlorophenols in the environment.

    5.1.1  Air

        No information is available on the ambient levels of
    chlorophenols, other than PCP, in the atmosphere. The data on PCP are
    limited but may provide a useful indication of the potential for
    atmospheric distribution of the other chlorophenols. Measurable
    quantities of PCP are present in ambient air, and are surprisingly
    ubiquitous: Cautreels et al. (1977) detected 0.93 and 0.25 ng PCP/m3
    in the mountains high above La Paz, Bolivia, a presumably
    uncontaminated environment. Concentrations at 4 sites in Antwerp,
    Belgium, ranged from 5.7 to 7.8 ng PCP/m3. It is not known whether
    the compound was present as a vapour, or adsorbed on airborne
    particulates. Presumably as a result of such transport, chlorophenols
    have been detected in rainwater, alpine lakes, and snow (Bevenue et
    al., 1972; Paasivirta et al., 1985).

    5.1.2  Water

        Residues of all chlorophenol isomers have been detected in aquatic
    systems. Generally, residues are present at measurable concentrations
    in discharges from such sources as manufacturing plants,
    wood-treatment facilities, municipal waste discharges, and in the
    receiving waters adjacent to these sources. Concentrations in other
    receiving waters are more sporadic and quite low. While the levels are
    low, chlorophenols have been detected in some of the least polluted
    waters in the world.

        Most reports of chlorophenol levels in water are from sites in the
    vicinity of wood-treatment facilities. For instance, Fox & Joshi
    (1984) measured concentrations of PCP and tetrachlorophenols in water,
    sediments, and selected biota from the Bay of Quinte, in an
    investigation of contamination by a wood-treatment plant. Levels of
    both T4CP (2,3,4,5 plus 2,3,5,6) and PCP generally declined with
    increasing distance from the source. Adjacent subsurface water levels
    of T4CP ranged from 0.005 to 0.086 g/litre over the summer of 1978,
    while at the furthest site, 100 km distant, the range was 0.005-
    0.030 g/litre. Surface film samples contained T4CP concentrations
    from 2.3-200 times higher than those below the surface. Bacon (1978)

    assayed chlorophenols in the effluent from a Kraft pulp-mill at St.
    John, New Brunswick, and found 2,4-DCP and 2,4,6-T3CP in the samples
    before and after chlorination and caustic extraction. No chlorophenols
    were detected in the receiving waters, perhaps as a result of tidal
    flushing. Similarly, in a Great Lakes survey conducted by the Ontario
    Ministry of the Environment (Jones, 1981), chlorophenol congeners were
    detected in receiving waters: samples from the St. Mary's River near a
    pulp and paper-mill did not contain any detectable levels of
    chlorophenols, while 1 of 10 samples taken from near another mill on
    Thunder Bay, contained 4 g DCP/litre, and 2 contained 3 and 23 g
    T3CP/litre, respectively.

        An Environment Canada survey (1979) of British Columbia coastal
    waters for chlorophenol contaminants in surface waters, effluents,
    sediments (section, and biota (section 5.1.6) did not reveal
    any DCP or T3CP residues in water samples, but low levels of T4CP
    (and PCP) were present at almost all sites: tetrachlorophenol
    concentrations ranged from trace levels to 1.0 g/litre in fresh
    waters and 5.2 g/litre in sea water. Effluent concentrations of T4CP
    were high at 2 out of 4 discharges sampled (530 and 8270 g/litre),
    even exceeding PCP levels. Garrett (1980) reported sources and levels
    of chlorophenols in sediments (section, fish (section 5.1.6),
    and a variety of discharges from industry, waste disposal systems, and
    runoff from landfills in the lower Fraser River and estuary. The most
    frequently detected chlorophenols were 2,4,6-T3CP, 2,3,4,6-T4CP, and
    PCP. Levels in most discharges were less than 7 g/litre. Discharges
    from municipal sewage-treatment plants in the same study also
    contained several chlorophenols, most frequently 2,4,6-T3CP
    (trace-1.2 g/litre), 2,3,4,6-T4CP (trace-28.3 g/litre) and PCP.

        As in the Canadian studies, levels in receiving waters in the USA
    are typically low. Morgade and co-workers (1980) did not find any
    detectable levels of chlorophenols, other than PCP, in drinking-waters
    in Dade County, Florida.  In vitro chlorination of secondary sewage
    effluent and power plant cooling waters, using chlorine levels and
    treatment times similar to those used in practice, yielded only
    g/litre quantities of 2-MCP, 3-MCP, and 4-MCP (Jolley et al., 1975).

        Pierce & Victor (1978) measured the levels of PCP and some of its
    degradation products (2,3,5,6-T4CP and PCP-OCH3) in a Mississippi
    lake contaminated by an overflow from a wood pole-treatment plant.
    Prior to the spill, levels of 2,3,5,6-T4CP in the water were low,
    ranging from 0.07 to 0.21 g/litre. Concentrations were higher after
    the spill (0.25-2 g/litre), and remained relatively stable for at
    least 4 months. Sediment (section and fish tissue (section
    5.1.6) samples were also collected.

        Dutch research workers have monitored chlorophenol levels in the
    water and sediments of the major rivers in industrial areas in the
    Netherlands since 1976 (Wegman & Hofstee, 1979; Wegman & van den
    Broek, 1983). In both reports, maximum levels of all chlorophenols,
    other than PCP, seldom exceeded 1 g/litre. Medians for the most
    frequent congeners for 6 rivers in 1976 and 1977 ranged as follows:
    2,6-DCP, trace-0.15 g/litre; 2,4,5-T3CP, trace-0.15 g/litre;
    2,4,6-T3CP, trace-0.19 g/litre; 2,3,4,6-T4CP, trace-0.11 g/litre
    (Wegman & Hofstee, 1979). Likewise, Piet & de Grunt (1975) reported
    that levels of monochlorophenols ranged from not detectable to
    20 g/litre, dichlorophenols from not detectable to 1.5 g/litre, and
    trichlorophenols from not detectable to 0.1 g/litre in Netherland
    rivers and coastal waters. These ranges include the levels reported by
    Zoeteman (1975) for Rhine river water and drinking-water. Zoeteman et
    al. (1981) compiled information on concentrations of a variety of
    chemicals in Dutch ground waters. The highest concentrations of
    chlorophenols reported were as follows: 2,3,6-T3CP, 1 g/litre;
    2,4,5-T3CP, 2 g/litre; 2,3,4,6-T4CP, 3 g/litre; 2,3,5,6-T4CP,
    5 g/litre; PCP, 1 g/litre.

        In the Glatt river in Switzerland, concentrations of 2,3,4,6-T4CP
    over the year averaged about 0.04-0.05 g/litre at each of several
    stations along a 35-km stretch of the river (Ahel et al., 1984).

        Paasivirta et al. (1985), assayed water, snow, ash, benthic
    invertebrates, fish, and birds from relatively unpolluted Finnish
    lakes for chlorophenol residues. (Levels in the biota are reported in
    section 5.1.6). The compounds 2,6-DCP, 2,4-DCP, 2,4,6-T3CP,
    2,4,5-T3CP, 2,3,4,6-T4CP, and PCP were widespread, and present at
    g/litre concentrations in pulp-bleaching liquors and ng/litre levels
    in lake waters (Table 10). Chlorination of some waters elevated the
    concentration of the total chlorophenols measured almost 6-fold, from
    0.043 g/litre to 0.243 g/litre. Elevated levels have been associated
    with specific discharges in Europe. Leachate from a Danish chemical
    dump site used during 1953-71 contained, among other compounds, PCP
    and T4CP, the latter ranging in concentration from 0.030 to
    80 g/litre (Folke et al., 1984). Folke (1984) analysed effluent from
    a Danish sewage-treatment plant, which received a portion of its
    wastes from the manufacture of phenoxy herbicides, for a number of
    chlorophenols. The effluent contained 0.1 g 2-MCP/litre, 0.03 g
    4-MCP/litre, 0.5 g 2,4-DCP/ litre, 0.6 g 2,6-DCP/litre, 8 g
    2,4,6-T3CP/litre, and 0.03 g 2,3,4,6-T4CP/litre.

        Table 10.  Concentration (g/litre) of chlorophenols in Finnish pulp mill waste
               liquors and fresh watersa

    Chlorophenol                            Type of sample

                    Waste liquorsb   Fresh watersb     Janakka water   Jyvaskyla
                                                       raw     tap     tap

    2,6-DCP         ND - 12c         ND - 0.073        0.010   0.062   0.272
    2,4-DCP         ND - 11          ND - 0.014        0.014   0.053   0.093
    2,4,6-T3CP      15 - 28          ND - 0.011        ND      0.030   0.014
    2,4,5-T3CP      ND - 66          ND - 0.019        0.019   0.059   0.035
    2,3,4,6-T4CP    ND - 10          ND - 0.090        ND      0.016   0.009
    PCP             ND - 01          0.064 - 0.011             0.023   0.005

    a  From Paasivirta et al. (1985).
    b  Range reported.
    c  ND -- Not detectable.

        A similar variety of congeners was detected in effluent from a
    sewage-treatment plant that was processing paper-mill wastes.
    Lindstrom & Nordin (1976) found 115 g 2,4,6-T3CP/litre in spent
    bleach liquors from kraft mill pulp chlorinated  in vitro, and noted
    that dichlorophenols were also present.

        As in Canada, high concentrations of chlorophenols in European
    fresh waters are associated with wood-treatment facilities. Waters on
    the sites of 2 Finnish sawmills, in which a sodium chlorophenate
    preservative (mostly Na-2,3,4,6- T4CP, with substantial quantities of
    the 2,4,6-T3CP and PCP salts) was used to protect against sapstain
    fungi, contained total chlorophenol concentrations ranging from 1.6 to
    20 000 g/litre. The highest concentration occurred in a blind drain
    adjacent to the dip site (Valo et al., 1984). Off-site levels in
    ground water and lake water were much lower, with a maximum of 1.17 g
    chlorophenols/litre. Concentrations of chlorophenols in the effluent
    from a Swedish sawmill on two separate dates were, respectively: 8.3
    and 24 g 2,4-DCP/litre; 40 and 22 g 2,4,6-T3CP/litre; 7.5 and
    5.8 g 2,3,4,6-T4CP/litre (Xie et al., 1986).

        Chlorophenols are also widespread in European marine waters,
    generally at lower concentrations than in fresh waters. Weber & Ernst
    (1978) noted that coastal waters off the Federal Republic of Germany
    yielded only trace quantities (1 ng/litre) of 2,4-/2,5-DCP, 2,6-DCP,
    2,4,5-T3CP, 2,4,6- T3CP, 2,3,4,5-T4CP, and 2,3,4,6/2,3,5,6-T4CP.
    Danish marine waters receiving chemical dump leachate including T4CP
    (at 0.030-80 g/litre) showed corresponding levels in water of
    0.006-0.008 g/litre (Folke et al., 1984). Chlorophenol levels in
    coastal waters off Sweden fell off rapidly with increasing distance
    from a sulfate pulp-mill, from maximum concentrations on one date of
    0.123 g 2,4-DCP/litre, 0.040 g 2,6-DCP/litre, 0.370 g
    2,4,6-T3CP/litre, and 0.084 g 2,3,4,6-T4CP/litre to undetectable
    levels (Xie et al., 1986). For example, the half-distances for
    2,4,6-T4CP and 2,3,4,6-T4CP disappearance were 1 and 0.8 km,
    respectively (see also sections 4.1.3,  Sediments

        Chlorophenol concentrations in sediments are for the most part
    much greater than those in the overlying water. This may reflect
    adsorption of the chlorophenols on suspended particulates in the water
    column, with subsequent sedimentation. For instance, Eder & Weber
    (1980) reported higher levels of chlorophenols (di- to penta-) in both
    sediments and suspended solids compared with those in water.

        Fox & Joshi (1984) analysed sediment cores for T4CP and PCP in
    their study of chlorophenol contamination from a wood-preservation
    facility on the Bay of Quinte, Lake Ontario. For the upper sediments
    (1/2-cm sections of the top 5 cm of the core) levels ranged from 1 to
    48 g/kg dry weight. In a similar study, Environment Canada (1979)
    analysed sediments in British Columbia waters associated with
    wood-preservation plants. T4CP was present at all 11 sites, and
    ranged from a trace to 1600 mg/kg dry sediment. T3CP was found at 4
    of the 11 sites, with as much as 170 g/kg of dry sediment measured.
    Although the kraft pulp-mill effluent studied by Bacon (1978)
    contained 2,4-DCP and 2,4,6-T3CP, only PCP was detected in sediment
    samples downstream.

        As a result of a PCP spill from a pole-treatment plant, sediments
    in a Mississippi lake were contaminated with PCP and its degradation
    products, including 2,3,5,6-T4CP (Pierce & Victor, 1978). Four months
    after the spill, the levels of 2,3,5,6-T4CP in surface sediment
    ranged from 3.8 to 71 g/kg dry sediment whereas, 1 month after the
    spill, levels of between 12 and 97 g/kg dry sediment had been

        Interpretation of these results is confounded by their
    variability, the residence time (several weeks) of PCP in the water
    column, and a 1974 spill at the same site. T4CP was present in the
    sediments of a nearby, reportedly uncontaminated, pond at 1 g/kg.

        High concentrations of DCP and T3CP were present in sediments
    adjacent to hazardous waste dumps near the Niagara River, at maximum
    levels of approximately 2000 and 500 g/kg, respectively (Elder et
    al., 1981).

        In studies in progress on chlorophenols that are present in
    surface and coastal waters and sediments in The Netherlands, the
    compounds 2,5-DCP, 2,3,5-T3CP, 2,4,5-T3CP, 2,3,4,5-T4CP,
    2,3,4,6-T4CP, and PCP are observed most frequently (Wegman & van den
    Broek, 1983). In the industrial regions that have been the focus of
    this research, moderate levels of contamination prevail (several g/kg
    of dry sediment for most isomers) (Table 11).

    Table 11.  Levels of chlorophenols (g/kg) in sediments from Dutch
               surface waters and the Weser estuary

    Compound      Lake Ketelmeera       Other Netherlanda     Weser
                                        surface waters        Estuaryb
                                        (Range)               (Mean)
                  Median    Maximum

    3-MCP            -       43
    2,3-DCP        1.9        2.2
    2,4-DCP        4.4       10            ND - 3.6           1.170
    2,5-DCP        6.3       11            ND - 3.8
    2,6-DCP        1.8       31            ND - 2.5
    3,4-DCP        9.8       49            ND - 4.1
    3,5-DCP        6.6       12            ND - 9.3
    2,3,4-T3CP     0.7        0.8          ND - 0.6
    2,3,5-T3CP     2.4       11            ND - 1.5
    2,4,5-T3CP     6.4       15            ND - 6.3           1.170
    2,4,6-T3CP     1.9        3.7          ND - 0.9           0.300
    3,4,5-T3CP     1.2       19            ND - 1.7           0.310
    2,3,4,5-T4CP   0.9        8.9          ND - 0.9
    2,3,4,6-T4CP   1.7        4.9          ND - 1.7           1.546
    2,3,5,6-T4CP   1.4        2.8          ND - 0.4

    a  From:Wegman & van den Broek (1983) (dry sediment).
    b  From: Eder & Weber (1980) (wet sediment).

        Paasivirta et al. (1980) analysed sediments and biota (section
    5.1.6) from three Finnish lakes for several chlorophenols and related
    compounds. In one lake, contaminated only from sawmills upstream,
    concentrations of T3CP and T4CP were 4.68 and 33.4 g/kg of
    sediment; respectively (Table 12, section, while in another
    lake downstream from a pulp-mill, the corresponding values were 27.7
    and 50.1 g/kg. The third lake, further downstream from pulp and paper
    inputs, contained intermediate levels of both compounds.

        Levels in estuarine and marine sediments overlap considerably with
    those from fresh waters. Butte et al. (1985) determined chlorophenol
    concentrations in sediments and clams (section 5.1.6) from a German
    bight that had received untreated PCP waste from a pulp and paper-mill
    for 13 or 14 years, until 2 years before the study. Sediments from one
    site near the former discharge contained from 28.3 to 30.9 g
    2,3,4,5-T4CP/kg of dry sediment, while those from another site
    contained 92.8 g 2,3,4,5-T4CP/kg and 7.9-11.6 g 2,3,4,6- plus
    2,3,5,6-T4CP/kg. Sediments taken some distance from the discharge
    contained only 1.2 g 2,3,4,5-T4CP/kg or less. Eder & Weber (1980)
    reported levels of chlorophenols (di- to penta-) that corresponded
    with the lower end of the range for The Netherlands surface waters;
    mean concentrations of chlorophenols other than pentachlorophenol
    ranged from 0.300-1.546 g/litre. Similar levels were found in Baltic
    Sea sediments from a site 2 km distant from a sulfate pulp-mill; these
    contained 0.9 g/kg dry sediment of 2,4-DCP, 0.4 g 2,4,6-T3CP/kg,
    and 3.1 g 2,3,4,6-T4CP/kg (Xie, 1983). In a subsequent study, higher
    levels of the same congeners were found at this location (Xie et al.,
    1986). While surface sediments from sites roughly 5-10 km from the
    discharge contained levels of chlorophenol that were near or below the
    limits of detection, sediments 2 km or less from the mill contained as
    much as 16 g 2,4-DCP/kg dry sediment, 19 g 2,4,6-T3CP/kg, and 89 g

    5.1.3  Soil

        Information on ambient levels of chlorophenol residues in soils is
    limited, perhaps reflecting limited use of these compounds on soils.
    The processes of degradation and movement also combine to reduce soil
    residues (section 4).

        The sole report on levels of chlorophenols in Canadian soils is
    undoubtedly atypical of the environment at large. Garrett (1980)
    reported that soil samples from the former site of a pesticide plant
    in Richmond, British Columbia contained 2 mg T4CP/kg dry soil,
    0.18 mg T3CP/kg, as well as low levels of PCP.

        Valo et al. (1984) assayed chlorophenols in the soil and water
    (section 5.1.2) around two Finnish sawmills where lumber was treated
    against sap-staining fungi. Soils at both facilities were heavily
    contaminated with chlorophenols; up to 70 mg/kg were found near the
    dipping site, and up to 6 mg/kg occurred in a storage area for the
    preserved wood. Soil outside the storage area contained only
    0.1 mg/kg. The most common chlorophenols in the preservative
    formulation also predominated in the near-surface soils, but lower
    chlorinated phenols (particularly dichlorophenols) became increasingly
    important further down the soil horizon, presumably as a result of
    decomposition of the preservative. In general, chlorophenol
    concentrations declined in the progressively deeper layers.

        Kitunen et al. (1987) determined the concentrations of
    chlorophenols and their contaminants in soil near the preserving
    facilities at 4 different sawmills. Concentrations of chlorophenols in
    soil ranged from 500 to 3500 mg/kg, polychlorinated phenoxyphenols,
    from 1-5 mg/kg, and polychlorinated dibenzofurans, from 0.2-5 mg/kg.
    No clear decrease in the soil concentrations of these compounds was
    seen during the first year after the mill stopped using technical

    5.1.4  Food, feed, and drinking-water  Food

        Little information is available on residues in food of
    chlorophenols, other than PCP. Low-level contamination undoubtedly
    occurs as a result of contact with treated wood storage and transport
    containers, and from herbicide applications. However, both of these
    uses are prohibited in a number of countries (section 3.2.2); hence,
    the following cases may overestimate the extent of contamination.

        Both T4CP and PCP were identified in agricultural products by the
    Alberta Department of Agriculture (Jones, 1981). Trace levels of T4CP
    (mainly 1 g/kg, maximum 45 g/kg) occurred in grab samples of
    carrots, potatoes, turnips, and beets. T4CP concentrations as high as
    472 g/kg occurred as a result of contamination from treated wood.

        No residues were detected in 45 samples of Southern Ontario milk
    analysed for 2,4,5-T3CP, 2,4,6-T3CP, 2,3,4,6-T4CP, and PCP (Frank
    et al., 1979).

        In the USA, Bristol et al. (1982) determined 2,4-DCP
    concentrations in 3 varieties of potatoes sprayed with 2,4-D as a
    growth regulator at an application rate of 140 g/ha. Levels of
    chlorophenol, which could arise as a contaminant or degradation
    product of the herbicides, varied slightly in 3 varieties of potatoes,
    but ranged between 3 and 8.8 g/kg. Potatoes not sprayed with 2,4-D
    did not contain any detectable 2,4-DCP.

        Stijve (1981) determined chlorophenol residues in edible products
    derived from the bones and hides industry, where PCP was used as a
    preservative and disinfectant. Fleshing grease intended as an
    ingredient in cow feed, contained 50-480 g 2,4,5-T3CP/kg, 2060-13
    400 g 2,3,4,6-T4CP/kg, and 210-1090 g PCP/kg. A survey of 50
    samples of edible gelatins (worldwide distribution), which are
    produced from the collagen in hides and bones, all contained PCP; 30%
    also contained 2,3,4,6-T4CP and trace amounts of trichlorophenols. In
    some countries, where chlorophenola are used for the disinfection of
    hides, chiorophenol levels in some gelatins range from 1000 to
    5000 g/kg.

        Chlorophenols have been found at very low levels in the tissues of
    commercial livestock and poultry. Fartington & Munday (1976) found
    2,3,4,6-T4CP (at 2-3 g/kg) in chicken flesh from 3 out of 4 shops in
    the United Kingdom.  Livestock feed

        No data are available on levels of the lower chlorophenols in
    animal feed. Jones (1981) cited a case in which a boxcar that had been
    used to ship PCP was later filled with feed oats, contaminating the
    oats with roughly 2000 mg PCP/kg. Presumably, the feed was
    simultaneously contaminated with T4CP at roughly 10% of the PCP
    levels, given the usual formulation for technical Na-PCP. Livestock
    illness and mortality were associated with this incident.  Drinking-water

        Data on chlorophenol residues in drinking-water are quite limited,
    but suggest that levels vary considerably between locations. Sithole &
    Williams (1986) reported that low levels of a number of lower
    chlorophenols occurred infrequently in potable waters at 40 Canadian
    treatment plants. Chlorination increased the concentrations of 2-MCP
    (maximum observed: 65 ng/litre), 4-MCP (127 ng/litre), 2,4-DCP
    (72 ng/litre), 2,6-DCP (33 ng/litre), and 2,4,6-T3CP (719 ng/litre),
    but decreased those of 2,3,4,5-T4CP (reduced below the limit of
    detection) and PCP (34 ng/litre). Lower chlorophenols were not
    detected in drinking-water supplies from Dade County, Florida (Morgade
    et al., 1980). Dietz & Traud (1978) found low concentrations of a
    variety of CP congeners in drinking-water from the Ruhr area of the
    Federal Republic of Germany, including: 3-6 ng 2,4-DCP/litre; 20 ng
    2,6-DCP/litre; 1 ng 2,4,6-T3CP/litre; 1 ng 2,3,5-T3CP/litre; 3 ng
    2,4,5-T3CP/litre; 1 ng 2,3,4,5-T3CP/litre; and 3 ng
    2,3,4,6-T4CP/litre. For comparison, levels in the effluent from a
    sewage plant were concurrently 2 orders of magnitude higher.

        In contrast, Paasivirta et al. (1985) found a number of
    chlorophenols in Finnish tap waters at levels roughly one order of
    magnitude higher than those in the German study (Table 10). As these
    data indicate, chlorophenol concentrations in drinking-water are
    generally quite low; indeed, the low threshold concentrations
    producing undesirable organoleptic (taste and odour) properties would
    make higher levels in drinking-water unacceptable (WHO, 1984 and Table

    5.1.5  Treated wood

        The treatment of wood continues to be an important use for
    chlorophenols (section 3.2.2), with considerable potential for
    environmental contamination, as well as general and occupational human
    exposure. In 1978-79, levels of chlorophenols, principally PCP, were
    measured in samples of wood shavings that were used as livestock
    litter in Southern Ontario (Jones, 1981). No trichlorophenols were
    detected, but T4CP, PCP, and related chlorinated anisoles were
    quantified. T4CP levels were as high as 70 mg/kg. Daniels & Swan
    (1979) determined that 15 lumber samples from a British Columbia
    sawmill protected with a commercial formulation of T4CP and PCP salts
    ("sodium penta") contained on average 44 g chlorophenols/cm2 (range,
    29-86 g/cm2), most of which was T4CP.

        In the United Kingdom, Parr et al. (1974) found that wood shavings
    from imported wood used as litter for hens were contaminated with the
    sodium salts of T4CP and PCP. When lumber is planed, most of the
    chlorophenates are removed in the shavings. As a result, levels of
    2,3,4,6-T4CP and PCP in fresh litter are quite high. According to
    Parr et al.(1974), T4CP concentrations averaged 54 mg/kg and ranged
    from 4 to 310 mg/kg. When the litter is used, chlorophenol levels fall
    off as they are converted to their corresponding chloroanisoles (Gee &
    Peel, 1974): spent litter contained on average 0.7 mg T4CP/kg.
    Similarly, Curtis et al.(1972) measured as much as 100 mg
    2,3,4,6-T4CP/kg in fresh shavings and sawdust from the United

        Levin & Nilsson (1977) assayed for T4CP, PCP, and related
    compounds in wood dust from a Swedish sawmill. The wood had been
    treated with 2% Na-2,3,4,6-T4CP; T4CP levels in the dust ranged from
    100 to 800 mg/kg.

    5.1.6  Terrestrial and aquatic organisms  Invertebrates

        Invertebrates contain levels of chlorophenols that are higher than
    those found in the environment at large, reflecting moderate
    bioconcentration by these organisms (section 4.2.2). Environment
    Canada (1979) found tetrachlorophenol in invertebrates from the
    receiving waters for wood-treatment plant effluents in British
    Columbia. In fresh waters, crayfish  (Pacifasticus sp.) pincer muscle
    contained traces of T4CP. The same tissue from a marine crab  (Cancer
     magister) contained T4CP levels ranging from a trace to 20 g/kg
    wet weight. One clam  (Macoma) sampled contained 12 g T4CP/kg,
    presumably in muscle tissue. T3CP was not detected in any of the
    organisms. Similar chlorophenol burdens were reported by Bacon (1978),
    who assayed for 2,4-DCP, 2,4,6-T3CP, and PCP in lipids from a clam
     (Mya arenia) and sandshrimp  (O'angon septemspinosa) from waters
    receiving pulp-mill effluent. Trace quantities of 2,4-DCP were present
    in both organisms, while 2,4,6-T3CP levels ranged from undetectable
    to 7.2 g/kg wet weight for the clam and 9.2 g/kg wet weight for the

        During the course of their survey of chlorophenol residues in the
    Weser Estuary and German Bight, Ernst & Weber (1978) determined that a
    polychaete  (Lanice conchilega) contained on average 11.8 g 2,4-DCP
    and 2,5-DCP/kg, 19.3 g 2,4,5-T3CP/kg, 26 g 2,4,6-T3CP/kg, 7 g
    2,3,4,5-T4CP/kg, 66.9 g 2,3,4,6-T4CP and 2,3,5,6-T4CP/kg, and
    117.5 g PCP/kg (all values wet weight).

        Paasivirta et al. (1980) have surveyed levels of chlorophenols in
    a variety of biota in 3 lakes with different chlorophenol inputs
    (section and Table 12). Plankton generally contained little or
    no tri-chlorophenol, but relatively high concentrations of
    tetrachlorophenol. Mussels  (Anodonta piscinalis) and sponges
     (Spongilla lacustris) contained moderate levels of both T3CP and
    T4CP. Chlorophenol burdens in organisms from the different lakes
    generally ranked in the same order as the perceived chlorophenol
    inputs into the 3 lakes.

    In more recent work (Paasivirta et al., 1985), mussels, chironomids,
    sponges, and fly larvae from Lake Vatia, 5 km downstream from a
    pulp-mill, were analysed for several chlorophenols. Low levels
    (usually not detected to 20 g/kg fresh weight) of chlorophenols were
    found in all invertebrates except sponges, which inexplicably
    contained 195 g 2,4-DCP/kg fresh weight and 22 g 2,4,6-T3CP/kg.

        Table 12.  Chlorophenol levels in various environmental compartments in three
               Finnish Lakes (g/kg wet weight, except for sediment, dry weight)a,b,c

    Population   Lake   N      Trichlorophenol             Tetrachlorophenol
                               X       S        CV         X      S      CV

                 Kd     8     0.79     1.6      2.03      20.2   40.0    1.98
    Pike         pd     6    17.3     18.1      1.05      11.1   14.9    1.34
                 Vd    10    13.6     19.1      1.40      19.0   12.4    0.65

    Roach        K      9    ND       ND                   2.19   1.82   0.83
                 P     10     4.67     5.29     1.13       6.41   3.42   0.53
                 V     10    55.9     53.4      0.96      11.5    8.26   0.72

    Mussel       K     10    ND       ND                   2.83   4.44   1.57
                 P      9     1.44     2.21     1.53       7.44   3.47   0.47

    Sponge       K      5     0.36     0.80     2.22       6.30   6.36   1.01
                 P      5     6.86     9.14     1.33       1.45   2.43   1.68
                 V      5     4.96     3.73     0.75       2.56   1.12   0.44

    Plankton     K      4    ND       ND                  ND     ND
    (100 m)     P      4    ND       ND                   9.28  10.0    1.08
                 V      4     2.45     4.90     2.00       9.90   1.73   0.17

    Plankton     K      4    ND       ND        7.95      15.6    1.96
    (25 m)      P      4    NO       ND        14.3      10.5    0.73
                 V      3    ND       ND        23.1       4.08   0.18

    Sediment     K      5     4.68    10.4      2.22      33.4   38.6    1.16
     (0-2 cm)    P      5    10.7     15.1      1.42      37.5   29.3    0.78
                 V      5    27.7     17.2      0.62      50.1   17.3    0.35

    a  From: Paasivirta et al. (1980).
    b  N = number of samples analysed;
       x = mean;
       s = standard deviation;
       cv = coefficient of variation.
    c  Wet weight of plankton was calculated from dry weight by multiplying by
    d  Lake areas: K = Konnevesi; P = Paijanne; V = Vatia.

        Butte et al. (1985) analysed clams from a German bight that had
    received untreated PCP-contaminated discharge from a paper-mill for a
    number of years (section Clams near the discharge contained
    0.7-55.6 g 2,3,4,5-T4CP/kg dry tissue, while those further away
    contained, at the most, 2.6 g 2,3,4,5-T4CP/kg and 0.2 g 2,3,4,6-
    plus 2,3,5,6-T4CP/kg. Similar low concentrations of 2,3,4,6-T4CP and
    PCP were found in blue mussels  (Mytilus edulis) from Danish coastal
    waters (Folke & Birklund, 1986). Tissue levels of T4CP averaged from
    0.2 to 2.9 g/kg fresh weight (1-23 g/kg dry weight) for mussels from
    various locations in 1985, with no obvious relation to a nearby
    chemical dump from which chlorophenols were leaching.  Fish

        In general, levels of chlorophenols in fish are similar to, or
    slightly higher than, those in invertebrates. Bacon (1978) studied
    chlorophenol levels in different tissues from several fish species
    from the St. John River estuary, New Brunswick, which receives
    pulp-mill effluents. Residues of 2,4-DCP and, 2,4,6-T3CP were
    detected, usually at several tens of g/kg wet weight and several
    g/kg wet weight respectively, in all tissues including muscle,
    viscera, skin, and liver (calculated from per-lipid-weight data in
    original publication). In some instances, levels in liver were much
    higher than this; concentrations as high as 242.9 g 2,4-DCP/kg and
    128 g T3CP/kg (wet weight) were measured. In surface and coastal
    waters in British Columbia, Environment Canada (1979) detected T4CP
    in marine and freshwater sculpins. Across all sites, skeletal muscle
    burdens averaged 30 g/kg wet weight, and ranged from a trace to
    100 g/kg. Levels were roughly an order of magnitude higher in liver.
    Similarly, Garrett (1980) reported that marine sculpins  (Leptocottus
     armams) from the lower Fraser River were the principal fish with
    detectable amounts of T4CP, averaging 24.9 g/kg wet weight, and
    ranging from a trace to 62 g/kg. Significant levels of T4CP were
    also found in squawfish, which averaged 10.5 g/kg wet weight and
    contained as much as 18 g/kg. Chlorophenol levels were higher in fish
    that were caught in the industrialized areas of the river. Spottail
    shiners  (Notropis hudsonius) from Lakes Erie and Ontario contained
    2,4,5-T3CP and 2,4,6-T3CP at maximum concentrations of 22 and
    33 g/kg (wet weight, whole fish), respectively (Canada-Ontario Review
    Board, 1981).

        Similar tissue concentrations have been detected in fish from
    European waters. In Finnish lakes spanning a gradient of chlorophenol
    inputs (Paasivirta et al., 1980), skeletal muscle of roach contained
    on average 0-55.9 g T3CP/kg wet weight, and 2.19-11.5 g T4CP/kg
    (Table 12). Chlorophenol concentrations in roach muscle were related

    to the chlorophenol inputs into the lake. In contrast, levels in pike
    skeletal muscle (average ranges 0.79-17.3 g T3CP/kg, and
    11.1-20.2 g T4CP/kg) bore no relation to chlorophenol inputs. In
    subsequent studies (Paasivirta et al., 1981, 1983, 1985), average CP
    levels in muscle of pike, burbot, ide, and roach taken from waters
    receiving pulp-mill discharges also fell within the same range, except
    in the case of heavily polluted waters.

        In Lake Tiiranselka, which receives a large volume of pulp-mill
    effluent, average concentrations of 2,4,6-T3CP and 2,3,4,6-T4CP in
    pike muscle were 37.02 and 125.02 g/kg wet weight, respectively. Two
    species of Baltic salmon analysed for chlorophenols contained similar
    levels of contamination to those found in fish from moderately
    polluted lakes (Paasivirta et al., 1985). Muscle tissue of salmon from
    2 rivers and a hatchery contained an average of 3 g 2,4,6-T3CP/kg
    fresh weight, 1.8 g 2,4,5-T3CP/kg, and 12.5 g 2,3,4,6-T4CP/kg.
    Fish collected in the vicinity of a pulp-mill effluent in Sweden
    contained 2,4,6-trichlorophenol and related compounds that were
    present in the discharge (Landner et al., 1977). Perch  (Perca
     fluviatilis) contained levels of 2700 g/kg in liver fat (62.1 g/kg
    fresh weight), while Northern Pike  (Esox lucius) contained
    400-500 g/kg (27.5-40.4 g/kg fresh weight).

        Extremely high chlorophenol levels have occurred as a result of
    accidental spills. Following contamination of a Mississippi lake by
    PCP in December 1976 (section, levels of the degradation
    product 2,3,5,6-T4CP in sunfish liver and muscle increased by 1-2
    orders of magnitude (Pierce & Victor, 1978) (Table 13). Four to 5
    months after the spill, liver levels in sunfish were approaching
    pre-spill levels, while levels in muscle tissue apparently cleared
    more slowly. Bass and catfish showed particularly high levels of T4CP
    after the spill, but unfortunately no baseline data were provided.  Other non-human vertebrates

        Data on chlorophenol concentrations in vertebrates other than fish
    or human beings are quite limited. Purple martin fledglings analysed
    for chlorophenol residues contained 2 g T4CP/kg (Jones, 1981). The
    tissue analysed was not specified. Levels of CP residues in eggs,
    embryos, and chick tissues of ring-billed gulls on the Ottawa and St
    Lawrence Rivers have been reported (NRCC, 1982). The compounds
    2,4-DCP, 2,4,5-T3CP, 2,4,6-T3CP, and PCP were present in most
    tissues, the highest concentrations occurring in liver and brain
    (Table 14). Paasivirta et al. (1985) measured chlorophenol residues in
    the muscle tissue of 45 juvenile starlings from southern Finland.
    Detectable levels of residues were not common: 2 birds contained 1 g
    2,3,4,6-T4CP/kg fresh muscle and 2 others contained 1 and 2 g
    2,4,6-T4CP/kg, respectively.

    Table 13.  Levels of 2,3,5,6-T4CP in tissues of fish from a
               Mississippi lake (USA) contaminated by PCP from a
               wood-pole treatment facilitya

    Date             Fish        Concentration (g/kg wet weight)
                                 Muscle             Liver

    October 11/76b   Sunfish 1      <1                30
                     Sunfish 2      <1                50

    January 6/77     Sunfish 1      95               950
                     Sunfish 2      60               NAc
                     Bass 2        300              1600
                     Bass 3        130              8200
                     Catfish 1     219              8500

    April 27/77      Sunfish 1      27                25
                     Sunfish 2      22               150
                     Catfish 1      82              1400
                     Catfish 2      41               940

    a  From: Pierce & Victor (1978).
    b  Spill in December, 1976.
    c  NA = not analysed.

    Table 14.  Range of concentrations (g/kg) of several chlorophenols
               in ring-billed gull eggs, embryos, and chick tissuesa

                  2,4-DCP       2,4,5-T3CP    2,4,6-T3CP

    Fresh eggs      0-176       0-26          12-87

    Embryos                     7             25

    Chick liver    14-210       0             47-157

    Chick brain   177-476       NDb           144-234

    a  From: NRCC (1982).
    b  ND = not detectable.

        The same authors analysed osprey eggs, and the pectoral muscle,
    brain, liver, eggs, and kidney of white-tailed eagles. 2,3,4,6-T4CP
    levels in osprey eggs ranged from 0 to 17 g/kg fresh weight; MCPs,
    DCPs, and T3CPs were not detected. Similarly, only 2,3,4,6-T4CP
    occurred (15-22 g/kg fresh weight) in fresh eagle eggs. Fresh eagle
    muscle tissue (2 samples) contained moderate levels of 2,4,6-T3CP (26
    and 50 g/kg respectively) and 2,3,4,6-T4CP (0 and 26 g/kg). Single
    samples of eagle brain, liver, and kidney revealed that all of these
    tissues contained chlorophenol residues, some at high levels; kidney,
    for example, contained 1017 g 2,4-DCP/kg.

    5.2  General Population Exposure

        The general population is exposed to chlorinated phenols through
    diverse sources and routes, which have been summarized by the NRCC
    (1982). Chlorophenols can be ingested as contaminants in food
    including produce sprayed with phenolic pesticides, flesh of livestock
    given feed contaminated with these pesticides, and general food items,
    usually at mg/kg levels (section 5.1.4).

        In addition, sub-g/litre quantities of chlorophenol congeners
    have been detected in drinking-water (section 5.1.4). These 2 routes
    of exposure are generally considered to be the major sources of
    exposure of the general population to chlorophenols (US EPA, 1980c).
    In addition, minor quantities may be taken up through the dermal and
    respiratory routes. Sources include industrial discharges (solid,
    liquid, atmospheric) of chlorophenolic wastes, exposure to treated
    wood, exposure to general consumer products including adhesives,
    textiles, wood-treatment products, mouth-washes and disinfectants, and
    break down products of hexachlorobenzene and phenoxy acid herbicides.

        Because of this diversity of sources of chlorophenols, there are
    no comprehensive estimates of the chlorophenol levels to which the
    general population is exposed. On the basis of preliminary estimates
    from the literature of total chlorinated phenol residues in food,
    water, air, and miscellaneous sources, the Canadian Department of
    National Health and Welfare (NHW, 1988) estimated typical
    non-occupational exposure to all chlorophenols to be:

          6.0 g/person per day in food
          2.8 g/person per day in water
          1.9 g/person per day in air
          2.0 g/person per day from other sources
         12.7 g/person per day in total (= 0.18 g/kg body weight per day
              for 70-kg adult).

        Similarly, the NRCC (1982) estimated that the total chlorophenol
    exposure per day in the general population in Canada was 10-30 g/
    person (0.17-0.50 g/kg body weight per day for a 60-kg adult). This
    estimate was based on the following assumptions: 6 g/person per day
    from food; 4 g/person per day from water; and 20 g/person per day
    from air. The last figure is extremely high, based on monitoring data,
    and was derived by assuming that indoor rooms were treated with a
    chlorophenol preservative. This figure should be considered tentative
    in view of the meagre data base available on environmental levels.

        On the basis of approximate levels of several trichlorophenols in
    drinking-water and fish flesh, SENES (1985) estimated the daily
    general population intake of each of 2,4,5-T3CP, 2,4,6-T3CP, and
    (2,3,5- + 2,3,6-) T3CP to be 0.44 g/person per day. If it is assumed
    that the uptake of each of the remaining 2 isomers is also
    0.44 g/person per day, the total T3CP intake would then be
    2.20 g/person per day.

        These low estimated levels of exposure are confirmed by the few
    studies in which the residue levels of lower chlorinated phenols have
    been determined in the general population. Although contamination
    generally appears to be widespread, the concentrations of
    chlorophenols in the tissues and fluids of people, not occupationally
    exposed, are extremely low.

        Kutz et al. (1978) determined the levels of pesticide-related
    phenolic residues in human urine samples from all over the USA with a
    limit of detection of 5-30 g/litre. In over 1.7% of 400 samples
    collected from the general population, 2,4,5-T3CP was present at a
    mean concentration of less than 5 g/litre, and a maximum of
    32.4 g/litre.

        In comparing different methods of detection of hexachlorobenzene
    and 2,4,5-T3CP in human serum and urine, Yost et al. (1984) found
    2,4,5-T3CP levels in the 2 fluids, in the USA, to be 0.25-
    6.7 g/litre and 0.25-1.9 g/litre, respectively. Samples were pooled
    from the general population, but neither the sample size nor the site
    of origin was specified.

        As part of the development of an analytical method for
    chlorophenols, Edgerton et al. (1980) determined chlorophenol
    concentrations in urine samples from the general population. The
    origin of the samples was not specified, but was presumably the
    southeastern USA. Chlorophenol concentrations ranged widely as

        2,6-DCP, 1-112 g/litre; 2,4-/2,5-DCP, 2-161 g/litre (mean,
    34.1); 3,5-DCP, 15-44 g/litre; 2,4,5-T3CP, 1-9 g/litre;
    2,4,6-T3CP, 1-6 g/litre; 2,3,4,6-T4CP, 2-15 g/litre.

        Similar levels of T4CP were found in urine samples from 25
    members of the general population in Barcelona, Spain (Gomez-Catalan
    et al., 1987). The mean urine concentration was 6.2 g/litre (standard
    error of mean = 1.6). No trichlorophenols were detected.

        In Dade County, Florida, where large quantities of lindane
    (gamma-HCH) and Bromophos ( O-(4-bromo-2,5-dichlorophenyl)  O,O 
    dimethyl-phosphorothioate) are used in agriculture, Morgade et al.
    (1980) measured the serum concentrations of 2,4-DCP, 2,3,5-, 2,4,5-,
    2,4,6-T3CP, 2,3,4,5-, 2,3,4,6-T4CP, and PCP in 58 female residents.
    In addition, 10 samples of human adipose tissue from autopsies were
    analysed for the same series of compounds. No detectable levels of any
    of the non-fully substituted chlorophenols were found in the serum or
    adipose tissue of the study group, but traces of PCP were found in the
    drinking-water and in both biological compartments.

        Williams et al. (1984) analysed adipose tissue from autopsies of
    male and female residents of Ottawa (n = 84) and Kingston (n = 91),
    Ontario, for organochlorine residues. Levels of 2,3,4,5-T4CP were
    typically 6 or 7 g/kg tissue, and did not differ significantly
    between locations or sexes. Tissues from Kingston contained roughly 3
    times more of other T4CPs (2,3,4,6 plus 2,3,5,6; male 24 g/kg;
    female 20 g/kg) than those from Ottawa (male 6 g/kg; female
    8 g/kg), but this difference was not statistically significant.

        These data support the hypothesis that the general population is
    exposed to very low levels of the lower-chlorinated phenols. However,
    estimates of this burden are highly speculative at present, as data
    are lacking for most congeners. Quantitative analyses for these
    compounds in meat, poultry, produce, and drinking-water are scarce.
    Atmospheric measurements have not been documented at all, and the
    extent of dermal absorption by the general population, assumed to be
    low, is not known.

    5.3  Occupational Exposure

        The potential for both acute and long-term exposure to
    chlorophenols may be heavy for workers from industries using these
    compounds. The routes of exposure for Canadian workers have been
    summarized by NRCC (1982); the same routes undoubtedly apply in most
    other countries. Large numbers of workers are exposed to
    chlorophenols, other than PCP, in the lumber industry, particularly in
    instances where lumber is surface-treated with Na-T4CP, during the
    dipping, sorting, handling, planing, trimming, or the grading of

    In-service treatment of wood by painters, wood preservation workers,
    or telephone linemen could result in similar dermal and inhalation
    exposure. Employees in the chemical industry, who are involved in the
    manufacture of chlorophenols or their derivatives, may also be exposed
    to high levels. The same is true of employees in manufacturing
    industries that use chlorophenols as preservatives, such as the
    photographic, paint, textile, rubber, construction, electrical,
    pharmaceutical, and disinfectant industries. Finally, employees
    working with products containing chlorophenols may be exposed, such as
    commercial applicators and farmers using phenoxy herbicides, or those
    exposed to treated wood in the fields of construction (carpentry), or
    railways. For such occupational exposures, inhalation and dermal
    absorption are the major routes of uptake.

        Unfortunately, there is little quantitative information on
    occupational exposure to low chlorine-substituted chlorophenols. As
    might be expected of such moderately volatile compounds, high
    atmospheric concentrations are found in work areas where they are in
    use. In addition, the body fluids of persons working in such areas
    contain elevated levels of chlorophenols. In general, concentrations
    of chlorophenols in air at chemical manufacturing plants can reach
    mg/m3 levels while much lower concentrations occur in facilities in
    the lumber industry that use chlorophenols.

        Ott et al. (1980) examined worker exposure to T3CP and 2,4,5-T at
    a manufacturing plant in the USA. The time-weighted average
    concentrations of T3CP in the air at work locations adjacent to the
    reactor, salt wheel, acid wheel, and dryer, were 2.1, 2.1, 9.7, and
    1.6 mg/m3 respectively.

        In a factory manufacturing PCP in Japan, crude exhaust air vented
    from a"drying room" contained 3.54 mg T4CP/m3 and 14.04 mg PCP/m3
    (Akisada, 1964). Urine-T4CP concentrations of personnel in the
    factory ranged from 0.07 to 0.37 mg/litre, compared with 0.01-
    0.03 mg/litre for unexposed persons.

        An industrial hygiene survey of worker exposure to chlorophenols
    and hexachlorobenzene at a PCP-production facility revealed that
    workers in different tasks were exposed to average concentrations of
    2,3,4,6- plus 2,3,5,6-T4CP of 0.016-0.320 mg/m3 in conjunction with
    several-times-higher exposures to PCP. The highest average exposures
    were experienced by handymen and block-casting workers (Marlow, 1986).

        Recent data from Kauppinen & Lindroos (1985) showed much lower
    average atmospheric chlorophenol levels in 10 Finnish sawmills,
    ranging from 24 to 75 g/m3. The values given are the sum of the
    three chlorophenols present, as the Na-2,3,4,6-T4CP formulation used
    also contained 10-20% 2,4,6-T3CP and 5% PCP. The highest mean
    concentrations in the general work place occurred at the site where
    the solution was prepared and at the machine stacking the lumber. Much

    higher levels were also detected inside the drying kilns, where
    chlorophenol concentrations averaged 5800 g/m3. Levels of
    2,4,6-T3CP were measured separately; particularly high concentrations
    were noted at the machine stacking site (58 g/m3) and the outdoor
    dipping site (44 g/m3), while it could not be detected at the
    preparation site. Average urine levels of T4CP and PCP (measured
    together) ranged from 0.10 to 3.3 mol/litre (approximately
    25-825 g/litre). The highest mean concentration occurred among the
    loaders at the trough dipping area (mean air levels 55 g/m3, dermal
    uptake substantial), while the other urine values parallelled the
    atmospheric readings in terms of relative concentration.

        Kauppinen (1986) reported that air concentrations of chlorophenols
    (T4CP and PCP combined) for a variety of tasks in Finnish plywood
    plants usually ranged from < 1 to 6 g/m3. The levels in air plus
    wood dust, where plywood was sawed, ranged from 3 to 6 g/m3 and were
    usually higher than those in air at work sites where wood dust was

        A detailed study of the chlorophenol exposure of sawmill workers
    in a pulp, paper, and sawmill complex in British Columbia was
    conducted by Embree et al. (1984). They divided the workers into 3
    groups: a control group of 351 workers in areas with no identifiable
    air contaminants; a group of 31 workers in close proximity to recently
    treated lumber, who did not have manual contact with it (airborne
    exposure); and a group of 40 who handled recently treated lumber
    (dermal plus airborne exposure). Air levels of chlorophenols were
    determined using personal monitors. Tetrachlorophenol levels in the
    plant air were elevated, and similar for the airborne group (3.3 
    2.1 g/m3; mean  standard deviation), and the dermal-plus-airborne
    group (3.0  2.7 g/m3). Serum levels were related to perceived
    exposure in a dose-dependent manner; tetrachlorophenol concentrations
    for the dermal-plus- airborne group (204  92 g/litre) were
    approximately twice those in the airborne group (112  136 g/litre),
    and 8 times those in the controls (26  7 g/litre). Urine levels for
    the 2 exposed groups were also dose-dependent (airborne 93 
    43 g/litre; dermal-plus-airborne 125  20 g/litre). Urine levels in
    the control group were not reported.

        Similar urine concentrations were reported for American
    wood-workers exposed to Permatox(R) (3% PCP, 21% 2,3,4,6- T4CP)
    (Kalman & Hortsman, 1983). Of 47 workers, 28 showed urine levels of
    more than 100 g 2,3,4,6-T4CP/litre, 13, levels between 20 and
    100 g/litre, and 6 levels of less than 20 g/litre. Air levels were
    reportedly below 25 g/m3. Because atmospheric concentrations were
    this low, the authors suggested that the individuals with the highest
    urine levels were taking up most of the dose through non-respiratory
    routes, most likely dermal. Over a 2-week holiday period, T4CP levels
    in the three groups declined by averages of 84%, 67%, and 34%,
    respectively, a slower rate of elimination than that found in
    experimental animals (section 6.4).

        Kleinman et al. (1986) and Fenske et al. (1987) also evaluated the
    extent and impact of occupational exposure to Permatox(R) in 100
    workers from a lumber-mill in Washington State. Plant air
    concentrations of T4CP ranged from 0.8 to 12.2 g/m3, while no PCP
    was detected (limit of detection 0.5 g/m ). It was estimated that
    dermal exposure accounted for 95% of the dose taken up by exposed
    workers. Average chlorophenol concentrations in the urine were higher
    for exposed workers than for controls (range of averages:
    T4CP-exposed = 31.2-497.5 g/litre, control = 6.3-28.7 g/litre;
    PCP-exposed = 57.4-102.8 g/litre, control = 28.9-38.8 g/litre).

        In a recent report, 230 sawmill workers in Finland were examined
    for urinary levels of chlorophenols (Lindroos et al., 1987). In
    occupations where dermal exposure was greatest, workers (n = 112) had
    a median urinary chlorophenol level of approximately 1.8 mg/litre
    (range, 0.02-49 mg/litre, assuming all chlorophenols were T4CP)
    whereas employees (n = 34) exposed mainly via the respiratory route
    had a median urinary level of 0.2 mg chlorophenols/litre (range,
    0.02-3.1 mg/litre). These results support the hypothesis of Kalman &
    Hortsman (1983) regarding the importance of the dermal route of
    exposure for chlorophenols.

        The chlorophenol levels in urine among workers handling imported
    lumber treated with 2,3,4,6-T4CP ranged from 0.13 to 2.2 mol/litre
    (30.2-510.4 g/litre, assuming all chlorophenols were T4CP) with a
    mean value of 0.86 mol/litre (199.5 g/litre) (Rappe et al., 1982).

        These exposure data are static, and, as such, give no information
    on the actual amount of chlorophenols taken up by a worker. In the
    course of designating permissible levels of chlorophenol exposure for
    regulatory purposes, the US EPA (1978) modelled the chlorophenol
    exposure experienced by a worker performing various tasks (Table 15).

        The exposure levels indicate that, as expected, occupational
    exposure to chlorophenols is much higher than non-occupational; these
    rates of uptake are 2 or more orders of magnitude higher than
    estimates of exposure of the general population to all chlorophenols
    summarized in section 5.2.

        However, the estimates of chlorophenol burdens given in Table 15
    are for 2,4,5-T3CP (the use of which has been discontinued in many
    countries), and are based on speculative scenarios that exaggerate
    worker exposure to this compound. Despite the longstanding concern for
    the potential health hazards associated with occupational exposure to
    chlorophenols, meaningful estimates of worker exposure to the
    chlorophenols that are currently extensively used do not appear to
    have been made to date. Exposures have been estimated qualitatively

    or, at best, semi-quantitatively. Although occupational uptake of
    chlorophenols is thought to be principally through inhalation and
    dermal absorption, there are no data on the rates of such uptake. To
    obtain such information, air monitoring should be continuous
    throughout the shift, using personal monitors, and urine levels of
    chlorophenols should be measured for consecutive 24-h periods.

    Table 15.  Estimates of occupational exposure to 2,4,5-T3CPa

    Site                  Dermal exposure    Inhalation exposure
                               (g/kg body weight per day)

    Cooling tower              3.7b                23c
    Water Systems            14d                    90.3e
    Pulp and paper mill       2f                   55g
    Tannery                   49h                  87i
    Hospital                 70j                    9k

    a  From: US EPA (1978).
    b  Exposure to 100 ml containing 22 mg Na-2,4,5-T3CP/litre; 10%
       absorption for 60-kg female maintenance worker.
    c  100% relative humidity, 20 C; therefore, 1 m3 air contains
       0.0173 litre H2O with 22 mg Na-2,4,5-T3CP/litre H2O;
       breathing rate, 1.8 m3/litre for 2 h; 60-kg female worker.
    d  Exposure to 100 ml containing 87 mg Na-2,4,S-T3CP/litre; 10%
       absorption; 60-kg female worker.
    e  As footnote c, but product concentration 87 mg
       Na-2,4,5-T3CP/litre H2O.
    f  Exposure to 80 ml (13  10 ml; one hand) containing 15 mg
       Na-2,4,5-T3CP/litre; 10% absorption; 60-kg female worker.
    g  As footnote c, but product concentration 15 mg
       Na-2,4,5-T3CP/litre H20, 7-h exposure.
    h  Exposure to 1.4 litre containing 21 g Na-2,4,5-T3CP/litre;
       10% absorption;
    i  60-kg female worker. As footnote c, but product concentration
       21 g Na-2,4,S-T3CP/litre H2O, 8-h exposure.
    j  Exposure to 1 cup (0.24 litre; 16 cups per gallon) containing
       686 mg Na-2,4,S-T3CP per gallon; 10% absorption; 60-kg
       female worker.
    k  Hospital volume, 1800 m3; recommended air ventilation rate,
       60 m3/h per person; 60 persons; 8-h day; total circulated air,
       28 800 m3; 100 gallons disinfectant used; 100 cups remain giving
       a total of 4.3 g Na-2,4,5-T3CP; volatilization at 25 C;
       breathing rate, 1.8 m3/h; 8-h day; 60-kg worker.


    6.1  Absorption

        Hoben et al. (1976a) exposed male Sprague-Dawley rats to an
    aerosol of sodium-PCP (repeated exposures to about 5.9 mg PCP/kg body
    weight) and found very rapid absorption into the blood. Unfortunately,
    no information is available on the absorption of the lower chlorinated
    phenols via the mammalian lung during inhalation exposure.

        In general, chlorophenols are readily absorbed through the skin.
    Using the skin of the hairless mouse, Huq et al. (1986) found that
    aqueous solutions of 2-MCP, 2,4-DCP, and 2,4,6- T3CP readily
    penetrated the skin, provided that the compound was not ionized (i.e.,
    pH pKa).  In vitro studies on epidermal membranes from human skin
    taken at autopsy showed penetration by 2-MCP, 4-MCP, 2,4-DCP, and
    2,4,6-T3CP (Roberts et al., 1977, 1978). The lipophilic character of
    the solutes and their hydrogen-bonding capacity are the 2 main
    features determining this penetration. Shen et al. (1983) investigated
    the dermal absorption of T4CP in Sprague-Dawley rats and found the
    Na-2,3,5,6-T4CP was more toxic than 2,3,5,6-T4CP itself. Toxic
    amounts of 2,3,4,6-T4CP in organic solvents can be absorbed through
    the skin (Gosselin et al., 1976), and the use of 2,4,5-T3CP in
    hospitals has been suggested as a potential problem because of its
    absorption through the skin (US EPA, 1978). Similarly, on the basis of
    data concerning urine levels of chlorophenols, absorption through the
    skin has been reported to be a major route of exposure among workers
    occupationally exposed to chlorophenols or to their salts (section

        The greater part of orally-administered tri- and
    tetra-chlorophenols is recovered in the urine and faeces of test
    animals (section 6.4), indicating that lower chlorophenols are readily
    absorbed through the gastrointestinal tract. More than 90% of the oral
    dose was excreted in the urine of volunteers after ingestion of PCP,
    which indicates similarly effective absorption via the
    gastrointestinal tract in human beings (Braun et al., 1979).

    6.2  Distribution

    6.2.1  Tissue distribution following chlorophenol exposure

        No information is available on the distribution of
    mono-chlorophenols in animal systems.

        With respect to dichlorophenols, single intravenous injections of
    2,4-DCP (10 mg/kg body weight) in Sprague-Dawley rats weighing
    250-300 g resulted in a maximum concentration (17.7 mg/kg of tissue) in
    the kidney, 10 min after injection (Somani & Khalique, 1982). Levels
    in liver, brain, and fat peaked at 15 min at 10.5 mg/kg, 3.2 mg/kg,
    and 4.1 mg/kg tissue, respectively. A level of 1.64 mg/litre was
    recorded in plasma, 10 min after injection.

        Following intraperitoneal administration of 25 mg 2,4,6-T3CP/kg
    body weight to male Wistar rats (Pekari et al., 1986), concentrations
    in all tissues assayed were maximal, 30 min after injection: kidney
    levels peaked at 329  117 nmol/g, while maximum concentrations were
    progressively lower in blood, liver, fat, muscle, and brain.

        Hattula et al. (1981a) reported that Wistar rats fed 2,3,4,6-T4CP
    in olive oil at 100 mg/kg intragastrically for 55 days showed the
    following tissue concentrations of 2,3,4,6-T4CP: kidney, 5.1 mg/kg;
    spleen, 3.2 mg/kg; liver, 2.2 mg/kg; brain, 1.2 mg/kg; and muscle,
    0.46 mg/kg tissue.

    6.2.2  Tissue distribution following exposure to chemicals metabolized
           to chlorophenols

        The distribution of chlorophenols as metabolites following the
    administration of other organochlorine compounds has been investigated
    in several studies. Like the original chlorophenols, these metabolites
    accumulate most often in the kidney and liver. Clark et al. (1975)
    investigated the tissue distribution of 2,4-DCP in sheep and cattle
    fed 2,4-D. Cattle were given a diet containing 2,4-D at 0, 300, 1000,
    or 2000 mg/kg (9, 30, or 60 mg/kg body weight per day). Muscle, fat,
    liver, and kidney were analysed for 2,4-DCP. Sheep were given a diet
    containing 2,4-D at 2000 mg/kg for 28 days. At 2000 mg 2,4-D/kg in the
    diet, 2,4-DCP concentrations in kidney and liver from sheep were
    0.26 mg/kg tissue and 0.16 mg/kg tissue, respectively; in cattle,
    levels were 1.06 mg/kg and 0.31 mg/kg tissue, respectively.

        In laying hens fed VC-13 Nemacide(R) [ O-(2,4-dichlorophenyl)-
     O,O-diethyl phosphorothioate) at a dose of 800 mg/kg for 55 days,
    Sherman et al. (1972) reported similar levels of 2,4-DCP in both liver
    tissue and egg yolk (average values ranged from 0.122 to 0.613 mg/kg).
    2,4-DCP was not detected in the muscle and fat of these birds.

        Levels of 2,4,5,-T3CP in the tissues of sheep and cattle fed
    trichlorophenoxy acid herbicides for 28 days were determined by Clark
    et al. (1975). In sheep fed Silvex (2-(2,4,5- trichlorophenoxy)-
    propionic acid) at 2000 mg/kg, residues of 2,4,5-T3CP were 0.22 mg/kg
    in liver and 0.17 mg/kg in kidney.

        Cattle fed this compound at 9, 30, or 60 mg/kg body weight had
    2,4,5-T3CP tissue concentrations ranging from 0.06 to 0.48 mg/kg in
    the liver and from 0.05 to 0.10 mg/kg in kidney. No residues were
    detected in samples of muscle and fat from sheep or cattle fed Silvex.
    Sheep exposed to 2,4,5-T in the diet at 2000 mg/kg for 28 days
    exhibited 2,4,5-T3CP levels of 6.1 mg/kg, 0.90 mg/kg, 0.13 mg/kg, and
    0.05 mg/kg tissue, in the liver, kidney, muscle, and fat,

        Sheep dosed orally with Erbon(R) (2-(2,4,5-trichloro-phenoxy)
    ethyl 2,2-dichloropropionate) metabolized it to 2,4,5-T3CP and
    2-(2,4,5-trichlorophenoxy) ethanol in less than 7 h (Wright et al.,
    1970). Most of these compounds were eliminated in the urine (section
    6.4), but mg/kg quantities of 2,4,5-T3CP and the other metabolite
    were found in the kidney, liver, omental fat, muscle, and brain of
    sheep given 100 mg Erbon(R)/kg body weight daily for 10 days (5.54,
    3.14, 2.06, 1.00, and 0.21 mg/kg, respectively).

        Male Wistar rats dosed with 8 mg lindane (gamma-hexachlorocyclo-
    hexane)/kg body weight by gavage for 19 days showed 2,4,6-T3CP and
    2,3,4,6-T4CP in heart tissue, 2,3,4,6- T4CP and/or 2,3,5,6-T4CP in
    the liver, and 2,4,6-T3CP and 2,3,4,6-T4CP in the kidney (Engst et
    al., 1976), but no quantitative data were given.

    6.3  Metabolic Transformation

        The major metabolic transformation for the lower chlorinated
    chlorophenols appears to be conjugation with sulfate or glucuronate,
    prior to clearance in the urine. Perhaps, because of similarities
    between the structure and lipophilicity of T4CP and PCP, a small
    proportion of these congeners undergo the same dechlorination and/or
    oxidation reactions that PCP does prior to conjugation (Renner &
    Mcke, 1986).

        As much as 84.7% of administered 2-MCP was reportedly excreted as
    sulfate and glucuronate conjugates in dogs (Karpow, 1893). In the
    rabbit, oral administration of monochlorobenzene resulted in surf ate
    and glucuronide conjugates of 2-MCP in the urine (Lindsay-Smith et
    al., 1972). It has been suggested that in mice  o-methylation might
    be a relevant mechanism for 2-MCP detoxification (Angel & Rogers,
    1972). Similarly, conjugates were detected in the kidney, liver, fat,
    brain, and plasma of rats after the iv injection of 2.5-3 mg 2,4-DCP
    (10 mg/kg body weight) (Somani & Khalique, 1982). Of the total
    conjugates determined, glucuronide conjugates were the major

    metabolite in kidney (79.6%), liver (62.7%), brain (77.9%), and plasma
    (79.5%). No glucuronide conjugates were found in fat. Free 2,4-DCP did
    not accumulate in rat tissues and was rapidly metabolized to its
    conjugates. In another study using 14C-2,4-DCP on isolated perfused
    rat liver, Somani et al. (1984) demonstrated that the liver is capable
    of the formation of glucuronide conjugates, and that 2 dichlorometho-
    xyphenols are metabolites of 2,4-DCP when glucuronide formation is
    blocked by galactosamine (section 8.8).

        Bahig et al. (1981) have suggested that, in rats, 2,4,6-T3CP is
    isomerized to 2,4,5- and 2,3,6-T3CP before being excreted as
    glucuronide conjugates. However, in a similar study on rats given
    25 mg 2,4,6-T3CP/kg body weight (ip), 83  11% was present in the
    blood as glucuronides rather than being converted to another isomer
    (Pekari et al., 1986).

        Concerning T4CP, Ahlborg & Larsson (1978) showed that, of the 3
    isomers, only 2,3,5,6-T4CP was metabolized to a significant extent in
    the rat. Thirty-five percent of the given dose (10 mg/kg body weight
    by ip injection) was metabolized to tetrachloro- p-hydroquinone,
    which, when also given ip, is more toxic than the parent compound
    (section 8.9). Trichloro- p-hydroquinone was a minor metabolite of
    the other isomers. Recently, it has been shown that the microsomal
    metabolism of PCP yields tetrachloro-1,2-and tetrachloro-1, 4-hydro-
    quinone (van Ommen et al. 1986). Covalent binding to protein and DNA
    occurs via the corresponding tetrachloroquinones (van Oremen et al.,
    1988). To what extent this kind of metabolic activation plays a role
    in the toxicity of lower chlorinated phenols is not known, at present.

        The metabolism of compounds that axe structurally related to
    chlorophenols also yields conjugates of chlorophenols. Kurihara &
    Nakajima (1974) studied the metabolism in mice of injected 14C-hexa-
    chlorocyclohexane (14C-HCH). The major metabolites were conjugates of
    2,4,6-T3CP with sulfate or glucuronide, as well as conjugates of
    2,4-DCP. The proportion of 2,4,6-T3CP sulfate to glucuronide
    conjugates varied from 80%:20% to 40%:60%, depending on whether
    gamma-HCH or beta-HCH was used. Trace amounts of free 2,4,6-T3CP and
    2,4,5-T3CH were also found in the urine. Koransky et al. (1975) also
    found that injection of 14C-HCH into rats resulted in glucuronide
    and sulfate urinary metabolites of 2,4,6- and 2,4,5-T3CP; small
    amounts of the free phenols were also detected. The ratio of sulfate
    to glucuronide conjugates was not determined. Engst et al. (1976)
    found that lindane (gamma-HCH) administration in rats produced free
    2,4,6-T3CP, 2,3,4,6- and/or 2,3,5,6-T4CP and PCP in the urine, as
    well as glucuronide-bound 2,3,4-T3CP, 2,3,4,5-, 2,3,4,6- and/or

        In terms of glucuronide formation of PCP, the rat is probably a
    better model for human beings than the monkey, which does not
    metabolize this compound (Braun et al., 1978, 1979). Whether the rat
    model can be used to predict human responses to the lower chlorinated
    phenols is not known at present, since no human data exist. However,
    hydrolysis of human urine samples indicated that most of the T4CP in
    human urine is conjugated (Dahms & Metzner, 1979; Butte, 1984; Currie
    & McDonald, 1986).

    6.4  Elimination and Excretion

        In experimental mammals, chlorophenols are eliminated primarily in
    the urine. For example, Freitag et al. (1982) administered 14C-2,4,6-
    T3CP to rats orally for 3 days to examine retention, dispersion, and
    excretion rates. Within 7 days, 82.3% of the label was excreted in the
    urine and 22.2% in the faeces. At sacrifice on the 8th day, residues
    in the liver, lung, and adipose tissues were below the level of
    detection (i.e., less than 0.01% of the label), whereas the carcass
    retained 7.8% of the label. Bahig et al. (1981) found that 92.5% of a
    daily oral dose (25 g by gavage) of 14C-2,4,6-T3CP was excreted by
    rats in the urine, while 6.4% was found in the faeces. Thus, the
    ingested 2,4,6-T3CP was largely eliminated within 24 h. Similarly,
    Ahlborg & Thunberg (1980) reported that 2,4,5-T3CP given to rats was
    excreted rapidly (within 24 h) with very little retention by the
    animal, and Pekari et al. (1986) estimated the half-times for the
    elimination of 2,4,6-T3CP from the blood, liver, muscle, fat, brain,
    and kidney of rats at between 1.4 and 1.8 h, after dosing ip with
    25 mg/kg body weight.

        Excretion by rats of the different T4CP isomers injected
    intraperitoneally was examined by Ahlborg & Larsson (1978). While
    2,3,5,6-T4CP was eliminated in the urine within 24 h and
    2,3,4,6-T4CP within 48 h, only 60% of the injected 2,3,4,5-T4CP was
    collected in 72 h.

        In a study on the elimination of 2,4,-DCP from various tissues in
    the rat following intravenous administration of 10 mg/kg body weight
    (Somani & Khalique, 1982), the compound was eliminated most rapidly
    from brain tissue followed by plasma, fat, liver, and kidney.
    Half-lives for 2,4-DCP were 6 min in the brain, 10 min in fat and
    plasma, 15.1 min in the liver, and 30.1 min in the kidney.

        Much of the information on the excretion of chlorophenols has come
    from studies of the uptake and clearance of chlorophenols that have
    been formed metabolically from other compounds. As in the studies
    described previously, these chlorophenols are generally eliminated
    rapidly in the urine. Thus, Lindsay-Smith et al. (1972) identified
    free and conjugated forms of all monochlorophenol isomers in the urine

    of rabbits dosed with 14C-monochlorobenzene. Similarly, 2,4-DCP was
    eliminated in the urine of rats injected with Nemacide(R) (67% of
    dose excreted as 2,4-DCP within 3 days) (Shafik et al., 1973). Shafik
    et al. (1973) also found that rats cleared 53% of a dose of
    Ronnel(R) ( O, O-dimethyl- O (2,4,5-trichloro-phenyl)phosphoro-
    thioate) as 2,4,5-T3CP within 2 days. A sheep given 50 mg/kg body
    weight of Erbon(R) [2-(2,4,5-trichloro-phenoxy)-ethyl 2,2-dichloro-
    propionate] as an oral drench metabolized it to 2,4,5-T3CP and
    2-(2,4,5-trichloro-phenoxy) ethanol in less than 7 h (Wright et al.,
    1970). Within 96 h, 68.42% of the dose was eliminated in the urine and
    1.74% in the faeces, approximately half of these amounts as

        Karapally et al. (1973) identified chlorinated phenols derived
    from lindane in rabbit urine. Of the 14 chlorophenols identified,
    comprising at least 19.9% of the total dose, the most abundant were
    (in decreasing order) 2,4,5-T3CP, 2,3,5-T3CP, 2,4,6-T3CP,
    2,3,4,6-T4CP, 2,3-DCP, 2,4-DCP, and 2,3,4-T3CP. The results of a
    similar study on the rat (Engst et al., 1976) showed that 2,4,6-T3CP,
    2,3,4,6-T4CP and/or 2,3,5,6-T4CP, and 2,3,4,5-T4CP derived from
    lindane were eliminated via the urine. Chadwick & Freal (1972)
    observed that, following one week of dosing with lindane, rats
    excreted 3,4-DCP, 2,4,5-T3CP, 2,3,5-T3CP, 2,4,6-T3CP,
    2,3,4,5-T3CP, and 2,3,4,6-T4CP for at least 1 month.

        The clearance from tissues of chlorophenols derived from other
    compounds may be slower than their elimination via the urine. Sherman
    et al. (1972) found that from 60 to 83% of the 2,4-DCP metabolized
    from Nemacide(R) disappeared from the liver of chickens within 21
    days of the cessation of dosing. 2,4-DCP found in the yolk of eggs
    from these hens dropped to non-detectable levels in 10 days for the
    high-dose (800 mg/kg diet) group, while at the lower dosages (50, 100,
    200 mg/kg diet), a shorter time was required for complete clearance
    (see also section 6.2). In sheep fed 2,4,5-T3CP at 2000 mg/kg diet
    (Clark et al., 1975), liver and kidney 2,4,5-T3CP levels remained
    relatively constant one week after exposure ceased, while muscle
    concentrations dropped roughly 3-fold.


        There are few studies on the effects of chlorophenols, other than
    PCP, on organisms in the environment. This lack of information may
    stem, in part, from the fact that many wastes contain other
    potentially toxic components in addition to chlorophenols. Moreover,
    most laboratory studies on the toxicity of chlorophenols for
    environmental organisms have involved much higher exposure levels than
    those that are usually found in the environment.

        The information that is available on the effects of chlorophenols
    deals primarily with aquatic habitats, perhaps because many point
    discharges of chlorophenols are released into water bodies.

    7.1  Laboratory Studies

    7.1.1  Acute toxicity

        Recent laboratory studies on the acute toxicity of chlorophenols
    for aquatic biota are summarized in Table 16. The data are derived
    primarily from studies published since 1980; information from research
    prior to this date is presented by Jones (1981). In general, the
    patterns evident in the review by Jones (1981) are also seen in the
    more recent data (Table 16).

        Considerable overlap exists in the chlorophenol levels that
    produce toxic effects in bacteria, phytoplankton, macrophytes,
    invertebrates, and fish (Table 16). For instance, LeBlanc (1984)
    (Table 16) reported that LC50 values compiled for 4-MCP toxicity in
    algae  (Selenastrum, capricornutum, Skeletonema costatum),
    invertebrates  (Daphnia magna), and fish  (Lepomis macrochirus,
     Cyprinidon variegatus) ranged from 3.27-5.35 mg/litre. Most of the
    EC50/LC50 values for other organisms compiled in Table 16 also fall
    within the several mg/litre range. However, there are isolated reports
    of certain bacterial, fungal, and protozoan processes that are
    insensitive to chlorophenol exposure (Table 16).

        In general, chlorophenol toxicity for aquatic organisms increases
    with the degree of chlorination of the phenol ring (Table 16),
    presumably as a result of increasing lipophilicity (Table 3).

        Table 16.  Acute toxicity of chlorophenols for aquatic biota

    Test organism      Test          Chlorophenol   Concentration        Criterion                    Reference
                       conditions                   (mg/litre)

    Scenedesmus        SB, FW        3,5-DCP           5.32 (EC50)       Growth rate, Weibull model   Christensen & Nyholm
    spicatus                                           5.87 (EC50)       Growth rate, Probit model    (1984)
                                                       6.10 (EC50)       Growth rate, Logit model
    Selenastrum        SB, FW        4-MCP             5.01 (EC50)       Growth                       LeBlanc (1984)

    Skeletonema        SB, FW        4-MCP             3.27 (EC50)       Growth                       LeBlanc (1984)

    Bacillus sp.       SB, FW        2-MCP           700
                                     3-MCP           450
                                     4-MCP           400
                                     2,3-DCP         130
                                     2,4-DCP          75
                                     2,5-DCP          85
                                     2,6-DCP         550
                                     3,4-DCP          52                 IC50c reduction in           Liu et al. (1982)
                                     3,5-DCP          25                 activity after 30 min
                                     2,3,4-T3CP       13                 incubation with toxicant
                                     2,3,5-T3CP       10
                                     2,3,6-T3CP      190

    Table 16.  (cont'd).

    Test organism      Test          Chlorophenol   Concentration        Criterion                    Reference
                       conditions                   (mg/litre)


    Bacillus sp.                     2,4,5-T3CP       12
    (contd).                         2,4,6-T3CP      240
                                     3,4,5-T3CP        5
                                     2,3,4,5-T4CP      4
                                     2,3,5,6-T4CP     54

    Photobacterium     SW            2-MCP            33.8                                            Ribo & Kaiser
    phosphoreum                      3-MCP            14.1                                            (1983)
    (Microtox(R))                    4-MCP             8.30
                                     2,3-DCP           4.92
                                     2,4-DCP           5.52
                                     2,5-DCP           9.38              EC50 for inhibition
                                     2,6-DCP          13.2               of light emission with
                                     3,4-DCP           1.63              30-min toxicant exposure
                                     3,5-DCP           2.77
                                     2,3,4-T3CP        1.25
                                     2,3,5-T3CP        1.11
                                     2,3,6-T3CP       12.7
                                     2,4,5-T3CP        1.27
                                     2,4,6-T3CP        7.68
                                     3,4,5-T3CP        0.359
                                     2,3,4,5-T4CP      0.176
                                     2,3,4,6-T4CP      1.27
                                     2,3,5,6-T4CP      2.22

    Table 16.  (cont'd).

    Test organism      Test          Chlorophenol   Concentration        Criterion                    Reference
                       conditions                   (mg/litre)

    Activated          SB, FW        3,5-DCP          30.2               IC50 for O2                  Dutka & Kwan
    sludge                                                               consumption, 3 h             (1984)

    Photobacterium     SW            2-MCP            22.1               EC50 for inhibition          Indorato et al.
    phosphoreum                      2,4-DCP           3.36              of light emission with       (1984)
                                                                         toxicant exposure

    Activated          SB, FW        3,5-DCP           7                 EC50 for O2                  King (1984)
    sludge                                                               consumption

    Nitrifying                       5                                   EC50 for nitrate and
    activated                                                            nitrite production

    Photobacterium     SW            3.2                                 EC50 for light emission

    Sewage                           8                                   EC50 for growth inhibition,
    microorganisms                                                       6 h

    Sewage                           6                                   EC50 for growth inhibition,
    microorganisms                                                       16 h

    Sewage effluent                  15                                  EC50 for BOD, 5 days,

    Table 16.  (cont'd).

    Test organism      Test          Chlorophenol   Concentration        Criterion                    Reference
                       conditions                   (mg/litre)


    Photobacterium     SW            3,5-DCP           2.9               EC50 for light emission      Dutka & Kwan (1984)
    phosphoreum                                                          after 15 min

    Pseudomonas        SB, FW        3,5-DCP           3.2               EC50 for growth              Dutka & Kwan (1984)
    fluorescens                                                          inhibition, 18 h

    Activated          FB, FW        2-MCP           104.4                                            Beltrame et al.
    sludge                           3-MCP            67.5                                            (1984)
                                     4-MCP            71.0
                                     2,3-DCP          55.1
                                     2,4-DCP          47.6
                                     2,5-DCP          50.2
                                     2,6-DCP          65.2               IC50 for phenol
                                     3,4-DCP          42.7               biodegradation
                                     3,5-DCP          58.3
                                     2,3,4-T3CP       27.4
                                     2,3,5-T3CP       22.3
                                     2,3,6-T3CP       39.3
                                     2,4,5-T3CP       23.6
                                     2,4,6-T3CP       42.0
                                     3,4,5-T3CP       19.6
                                     2,3,4,5-T4CP     20.4
                                     2,3,4,6-T4CP     40.5
                                     2,3,5,6-T4CP     44.3

    Table 16.  (cont'd).

    Test organism      Test          Chlorophenol   Concentration        Criterion                    Reference
                       conditions                   (mg/litre)


    Nitrobacter        SB, FW        2-MCP            50                 25 and 27% inhibition of     Wang & Reed (1984)
                                                                         nitrite uptake
                                     3-MCP            50                 0 and 15% inhibition of
                                                                         nitrite intake
                                     4-MCP            50                 0 and 5% inhibition of
                                                                         nitrite intake
                                     2,3-DCP          30                 96 and 73% inhibition of
                                                                         nitrite intake
                                     2,4-DCP          30                 21 and 77% inhibition of
                                                                         nitrite intake
                                     2,4,6-T3CP       10                 88 and 100% inhibition of
                                                                         nitrite intake

    Nitrosomonas       SB, FW        2-MCP           100                 24% loss in ATP              Parker & Pribyl
    europa                           2,4,6-T3CP      150                 17.6% loss in ATP            (1984)

    Escherichia        SB, FW        2-MCP           100                 6.5% loss in ATP
    coil                             2,4,6-T3CP      150                 12.9% loss in ATP

    Pseudomonas        SB, FW        2,3,4,5-T4CP     10                 0% reduction in CFUs,        Trevors et al.
    fluorescens                                                          1-h exposure                 (1982)
                                                      25                 86.6 and 87.2% reduction
                                                                         in CFUs, 1-h exposure
                                                      35                 99.4 and 99.9% reduction
                                                                         in CFUs, 1-h exposure
                                                      23.2               LC50 of CFUs, 1-h exposure

    Table 16.  (cont'd).

    Test organism      Test          Chlorphenol    Concentration        Criterion                    Reference
                       conditions                   (mg/litre)


    Tetrahymena                      2-MCP            67.97
                                     4-MCP            36.68              IC50 for growth              Schultz &
                                     2,4-DCP          15.00              at 60 h                      Riggin (1985)
                                     2,5-DCP          12.15
                                     2,4,6-T3CP        3.99
                                     2,3,5,6-T4CP      1.40


    16 fungal          SB            3-MCP           257.1               Average minumum              Ruckdeschel &
    strains,                         4-MCP           184.9               concentration for            Renner (1986)
    (14 genera)                      2,3-DCP          60.8               complete inhibition
                                     2,4-DCP          54.1               of growth
                                     2,5-DCP          54.8
                                     2,6-DCP         180.8
                                     3,4-DCP          30.1
                                     3,6-DCP          13.2
                       SB            2,3,4-T3CP       11.6
                                     2,3,5-T3CP      140.4
                                     2,4,5-T3CP       19.2
                                     2,4,6-T3CP        4.1
                                     2,3,4,5-T4CP      4.6
                                     2,3,4,6-T4CP     72.8
                                     2,3,5,-T4CP     119.7

    Table 16.  (cont'd).

    Test organism      Test          Chlorophenol   Concentration        Criterion                    Reference
                       conditions                   (mg/litre)

    Fungi (contd).

    Pichia             SB            Na-4-MCP        145                 IC50 for culture growth      Kwasniewska &
    (fermentative                    Na-2,4-DCP       42.5                                            Kaiser (1983)
    yeast)                           Na-2,4,5-T3CP     4.3

    Rhodoturula        SB            Na-4-MCP         62.5               IC50 for culture growth
    rubra                            Na-2,4-DCP       16.5
    (oxidative                       Na-2,4,5-T3CP     2.0


    Daphnia magna      SB, FW        2-MCP            22                 24-h LC50                    LeBlanc (1980)
    (water flea)                                       2.6               48-h LC50
                                     4-K4CP            8.8               24-h LC50
                                                       4.1               48-h LC50
                                     2,4-DCP        > 10                 24-h LC50
                                                       2.6               48-h LC50
                                     2,4,5-T3CP        3.8               24-h LC50
                                                       2.7               48-h LC50
                                     2,4,6-T3CP       15                 24-h LC50
                                                       6.0               48-h LC50
                                     2,3,4,6-T4CP    > 1.0               24-h LC50
                                                       0.29              48-h LC50
                                     2,3,5,6-T4CP      2.5               24-h LC50
                                                       0.57              48-h LC50

    Table 16.  (cont'd).

    Test organism      Test          Chlorophenol   Concentration        Criterion                    Reference
                       conditions                   (mg/litre)


    Daphnia magna                    2-MCP          17.95                IC50 for                     Devillers &
    (water flea)                     3-MCP          15.78                immobilization               Chambon (1986)
                                     4-MCP          8.07                 after 24 h
                                     2,3-DCP        5.19
                                     2,4-DCP        2.68
                                     2,6-DCP        9.38
                                     3,4-DCP        2.77
                                     3,5-DCP        2.09
                                     2,3,4-T3CP     2.24
                                     2,3,5-T3CP     2.28
                                     2,3,6-T3CP     7.38
                                     2,4,5-T3CP     2.08
                                     2,4,6-T3CP     5.47
                                     3,4,5-T3CP     0.88
                                     2,3,4,5-T4CP   1.76
                                     2,3,5,6-T4CP   2.27

    Astacus            SB, FW        2,3,6-T3CP     5.4 at pH 6.5        8-day LC50                   Kaila &
    fluviatilis                                     19.0 at pH 7.5       8-day LC50                   Saarikoski (1977)

    Mysidiopsis        SB, SW        4-MCP          29.7 at pH 6         96-h LC50                    LeBlanc (1984)

    Table 16.  (cont'd).

    Test organism      Test          Chlorophenol   Concentration        Criterion                    Reference
                       conditions                   (mg/litre)

    Invertebrates (contd).

    Palaemonetes       SS, SW        2,4-DCP        2.55(I)a; 2.16 (M)b  96-h LC50                    Rao et al. (1981)
    pugio                            2,4,6-T3CP     3.95(I); 1.21 (M)    96-h LC50
    (grass shrimp)                   2,4,5-T3CP     1.12(I); 0.64 (M)    96-h LC50
                                     2,3,4,5-T4CP   0.86(I); 0.37 (M)    96-h LC50
                                     2,3,4,6-T4CP   3.70(I); 0.81 (M)    96- LC50
                                     2,3,5,6-T4CP   4.10(I); 1.17 (M)    96-h LC50

    Palaemonetes       SS, SW        2,3,4,5-T4CP   0.30                 EC50 for intermolt           Rao et al. (1981)
    pugio                                                                limb regeneration
    (grass shrimp)                   2,3,4,6-T4CP   0.78                 EC50 for intermolt
                                                                         limb regeneration


    Pimephales         SB/FB, F-W    2-MCP          11.0-13.0            96-b LC50 flowthrough        Phipps et al.
    promelas                                        6.3                  192-h LC50 flowthrough       (1981)
    (fathead                                        9.7                  48-h LC50 static
    minnow)                          2,4-DCP        8.2-8.3              96-h LC50 flowthrough
                                                    6.5                  192-h LC50 flowthrough
                                                    8.4                  48-h LC50 Static
                                     2,4,6-T3CP     8.6-9.7              96-h LC50 flowthrough
                                                    5.8-6.4              192-h LC50 flowthrough
                                                    7.7                  48-h LC50 static

    Cyprinidon         SB, SW        4-MCP          5.7                  24-h LC50                    Heitmuller et al.
    variegatus                                      5.4                  48-h LC50                    (1981)
    (sheepshead                                     5.4                  72-h LC50
    minnow)                                         5.4                  96-h                         LC50
                                                    3.2                  NOECc

    Table 16.  (cont'd).

    Test organism      Test          Chlorophenol   Concentration        Criterion                    Reference
                       conditions                   (mg/litre)

    Fish (contd).

    Cyprinidon                       2,4,5-T3CP        2.4               24-h LC50
    variegatus                                         1.7               48-h LC50
    (contd).                                           1.7               72-h LC50
                                                       1.7               96-h LC50
                                                       1.0               NOECc
                                     2,3,5,6-T4CP      2.0               24-h LC50
                                                       2.0               48-h LC50
                                                       2.0               72-h LC50
                                                       1.9               96-h LC50
                                                       1.0               NOECc

    Salmo trutta       SB, FW        2,4-DCP           1.7               24-h LC50                    Hattula et al.
    (trout)                          2,6-DCP           4.0                                            (1981b)
                                     2,3,5-T3CP        0.8
                                     2,4,5-T3CP        0.9
                                     2,3,4,6-T4CP      1.1

    Poecilia           SS, FW        4-MCP            49.0 at pH 5       96-h-LC50                    Saarikoski &
    reticulatus                                       61.0 at pH 6       96-h LC50                    Viluksela (1981)
    (guppy)                                           66.0 at pH 7       96-h LC50
                                     2,4,5-T3CP       50.0 at pH 5       96-h LC50
                                                       6.3 at pH 7       96-h LC50
                                                      15.3 at pH 8       96-h LC50
                                     2,4,6-T3CP        3.1 at pH 5       96-h LC50
                                                       4.5 at pH 6       96-h LC50
                                                      11.6 at pH 7       96-h LC50
                                                      39.8 at pH 8       96-h LC50

    Table 16.  (cont'd).

    Test organism      Test          Chlorophenol   Concentration        Criterion                    Reference
                       conditions                   (mg/litre)

    Poecilia           SB, FW        2-MCP            13.5 at pH 7.8     24-h LC50                    Knemann &
    reticulatus                                        7.1 at pH 6.1     24-h IC50                    Musch (1981)
    (guppy)                          3-MCP             7.9 at pH 7.8     24-h LC50
                                                       6.4 at pH 6.1     24-h LC50
                                     2,4-DCP           5.9 at pH 7.8     24-h LC50
                                                       3.3 at pH 6.1     24-h LC50
                                     3,5-DCP           4.7 at pH 7.8     24-h LC50
                                                       2.6 at pH 6.1     24-h LC50
                                     2,3,5-T3CP        4.7 at pH 7.8     24-h LC50
                                                       0.88 at pH 6.1    24-h LC50
                                     2,3,6-T3CP       13.3 at pH 7.8     24-h LC50
                                                       0.94 at pH 6.1    24-h LC50
                                     3,4,5-T3CP        2.4 at pH 7.8     24-h LC50
                                     2,3,4,5-T4CP      1.1 at pH 6.1     24-h LC50
                                     2,3,5,6-T4CP      2.3 at pH 7.8     24-h LC50
                                                       0.44 at pH 6.1    24-h LC50
                                                       3.9 at pH 7.8     24-h LC50
                                                       0.36 at pH 6.1    24-h LC50

    Carassius          SB, FW        2-MCP            16                 25-h LC50                    Kobayashi et al.
    auratus                          4-MCP             9.0                                            (1979)
    (goldfish)                       2,4-DCP           7.8
                                     2,4,5-T3CP        1.7
                                     2,4,6-T3CP       10.0
                                     2,3,4,6-T4CP      0.75

    Table 16.  (cont'd).

    Test organism      Test          Chlorophenol   Concentration        Criterion                    Reference
                       conditions                   (mg/litre)

    Fish (contd).

    Lebistes           S8, FW        2-MCP            13.4               24-h LC50                    Benoit-Guyod et al.
    reticulatus                      3-MCP            27.0                                            (1984)
    (guppy)                          4-MCP             9.0
                                     2,3-DCP          18.0
                                     2,4-DCP           6.8
                                     2,5-DCP          11.0
                                     2,6-DCP           8.9

    Lebistes                         3,4-DCP           7.4
    reticulatus                      3,5-DCP           6.1
    (guppy)                          2,3,6-T3CP       53.0
                                     2,4,5-T3CP        2.7
                                     2,4,6-T3CP        2.3
                                     2,3,4,5-T4CP      1.70
                                     2,3,5,6-T4CP      3.60

    Lepomis            SB, FW        2-MCP             7.2               24-h LC50                    Buccafusco
    macrochirus                                        6.6               96-h LC50                    et al. (1981)
    (bluegill)                       4,-MCP            4.0               24-h LC50
                                                       3.8               96-h LC50
                                     2,4-DCP           4.7               24-h LC50
                                                       2.0               96-h LC50
                                     2,4,5-T3CP        0.61              24-h LC50
                                                       0.45              96-h LC50
                                     2,4,6-T3CP        0.72              24-h LC50
                                                       0.32              96-h LC50

    Table 16.  (cont'd).

    Test organism      Test          Chlorophenol   Concentration        Criterion                    Reference
                       conditions                   (mg/litre)

    Fish (contd).

                                     2,3,4,6-T4CP      0.19              24-h LC50
                                                       0.14              96-h LC50
                                     2,3,5,6-T4CP      0.40              24-h LC50
                                                       0.17              96-h LC50


    Lemna minor        SB, FW        4-MCP           282.8               50% chlorosis of fronds      Blackman et al.
    (duckweed)                       2,4-DCP          58.7                                            (1955)
                                     2,4,6-T3CP        5.9
                                     2,4,5-T3CP        1.7
                                     2,3,4,6-T4CP      0.6

    a  SB = Static bioassay.
       SS = Semistatic bioassay.
       SW = Marine.
       FB = Continuous flow bioassay.
       FW = Fresh water.
       M = Molting.
       I = Intermolt.
    b  NOEC = No-observed-effect concentration.
    c  IC50 = Concentration resulting in 50% inhibition.


        The position of the chlorines on the phenol ring also influences
    chlorophenol toxicity. Chlorophenols with chlorines in the 2 and 6
    positions are often relatively non-toxic (Kobayashi et al., 1979;
    Hattula et al., 1981b; Liu et al., 1982; Ribo & Kaiser, 1983;
    Devillers & Chambon, 1986; Ruckdeschel & Renner, 1986), perhaps,
    because the chlorines shield the hydroxyl group. These patterns
    parallel the biodegradability of the compounds, as ortho-substituted
    chlorophenols are less stable than their meta-substituted isomers
    (section However, the effects of chlorine position on
    toxicity are not evident in all of the studies included in Table 16,
    suggesting that the toxicity of any particular chlorophenol is highly

        In addition, pH affects the toxicity of chlorophenols (Table 16).
    At low pH, a given chlorophenol is relatively toxic, because it is
    mainly in the form of molecules that can readily cross biological
    membranes. As the pH is increased, chlorophenol toxicity is reduced
    because the ionic form becomes abundant. Under the range of conditions
    in most natural habitats, this effect becomes more important as the
    number of chlorines in the chlorophenol increases, because the pKa is
    related to chlorine number. Thus, monochlorophenol toxicity is
    relatively unchanged by environmental pH, whereas that of
    pentachlorophenol, which is present in the molecular form only under
    very acid conditions, is greatly affected.

        Studies on the toxicity of chlorophenols for terrestrial organisms
    in the environment are much more limited. Blackman et al. (1955)
    determined that the EC50s of several chlorophenols for the inhibition
    of radial growth of the mould  Trichoderma viride were as follows:
    4-MCP, 47.6 mg/litre agar; 2,4-DCP, 8.6 mg/litre; 2,4,6-T3CP,
    5.7 mg/litre; and 2,3,4,6-T4CP, 0.8 mg/litre. A similar pattern of
    increasing toxicity with increasing chlorination of chlorophenols was
    also observed by Sund & Nomura (1963) in their investigation of the
    inhibition of seed germination by a number of chlorophenols. In
    addition, they noted that chlorination at the 3 or 5 position enhanced
    chlorophenol toxicity for germinating seeds. In a survey on the
    contact toxicity of chemicals for the earthworm  Eisenia foetida
    (Roberts & Dorough, 1984), 2,4-DCP and 2,4,5-T3CP were classified as
    extremely toxic, on the basis that their 48-h LC50 values fell within
    the range of 1-10 g/cm2 of filter paper.

    7.1.2  Long-term toxicity

        There are very few studies on the long-term effects of
    chlorophenols on environmental organisms. Holcombe et al. (1982)
    exposed the embryo, larval, and early juvenile stages of fathead
    minnows to a range of sublethal concentrations of 2,4-DCP and other
    phenolic compounds, in 32-day flow-through tests using Lake Superior

    water. Survival of larvae and juvenile minnows was significantly
    reduced after exposure for 28 days to 2,4-DCP at 460 g/litre. The
    growth of larval and juvenile stages was reduced by 1240 g
    2,4-DCP/litre. Hatching success was unaffected by the maximum
    concentration used (1240 g/litre).

        Survival, reproduction, and growth were all reduced in  Daphnia
     magna exposed to 2,4-DCP concentrations of 1.48 mg/litre in
    long-term (21-day) static renewal tests (Gersich & Milazzo, 1988).

        In a study more relevant to field conditions, Virtanen & Hattula
    (1982) used a flow-through aquarium microcosm with levels of
    2,4,6-T3CP of 0.5 g/litre, in order to track its incorporation into
    sediment, algae, invertebrates, and fish. Male and female  Poecilia
     reticulatus fish were included in the microcosm, and aspects of
    their reproduction and histopathology were monitored. Over a 10-month
    period following their 56-day exposure in the aquarium and subsequent
    transfer to uncontaminated water, only 90 offspring were born to
    exposed fish and 22 of these died. Control fish produced 180
    offspring, only 8 of which died. In addition, several offspring from
    exposed parents had abnormally curved spines. Thus, under the test
    conditions, 2,4,6-T3CP appeared to be very fetotoxic, and perhaps
    teratogenic. No histological changes were noted in the livers or
    kidneys of  P. reticulatus as a result of these exposures.

    7.1.3  Organoleptic effects

        Exposure to low levels of chlorophenols can also impair the
    flavour of fish (see section 7.2.4). According to Boetius (1954), as
    little as 0.1 Ul 2-MCP/litre (v/v) tainted the flesh of eels and
    oysters after exposure for 11 and 4 days, respectively. Shumway &
    Palerisky (1973) estimated the threshold concentrations of several
    chlorophenols for the impairment of the flavour of rainbow trout to
    be: 2-MCP, 60 g/litre; 3-MCP, 25 g/litre; 4-MCP, 45 g/litre;
    2,3-DCP, 84 g/litre; 2,4-DCP, 1 g/litre; 2,5-DCP, 23 g/litre;
    2,6-DCP, 35 g/litre; and 2,4,6-T3CP, 52 g/litre.

    7.2  Toxicity Studies under Natural Environmental Conditions

    7.2.1  Bacteria

        During the course of studies in Dutch coastal waters, Kuiper &
    Hantsveit (1984) examined the effects of the addition of 4-MCP and
    2,4-DCP on plankton communities enclosed in 1500-litre plastic bags.
    In the first of 3 studies, total bacterial densities (by direct count)
    were prevented from increasing by 0.1 and 1 mg 2,4-DCP/litre but, in a
    second study, 2,4-DCP at 1 mg/litre did not have any effect on total

    bacterial densities, and, in the final study, 1 mg 2,4-DCP/litre was
    necessary to inhibit bacterial population growth. No effects of 4-MCP
    were detected, even at 1 mg/litre. As treatments were not replicated
    and bacterial densities were quite variable, it is not clear whether
    the effects observed were in fact responses to chlorophenol exposure.

        In contrast, when 5 mg 2,4,6-T3CP/litre was added to enclosures
    in a West German pond, the numbers of aerobic heterotrophic bacteria
    (by plate count) in the water increased more than 10 times compared
    with the controls, within 4 days (Schauerte et al, 1982). This
    response coincided with the disappearance of  Daphnia from the
    CP-treated tubes, suggesting that the increase was the result of a
    release from grazing by the  Daphnia.

        There has been some concern that chlorophenols in industrial
    wastes may impair the efficiency of secondary waste treatment through
    their toxic effects on bacteria. Using a bench-scale activated sludge
    plant, Broecker & Zahn (1977) determined that the degradation of waste
    water declined after exposure to 25 g 3,5-DCP/litre. Similarly, in a
    laboratory scale model of a trickling filter (El-Gohary & Nasr, 1984),
    exposure of acclimated microbes to 50 mg 2,4-DCP/litre reduced
    Biological Oxygen Demand (BOD), and Chemical Oxygen Demand (COD).
    However, chlorophenols in industrial wastes are unlikely to pose a
    serious hazard for organisms important for secondary treatment. Levels
    of chlorophenol entering treatment facilities are far below those used
    in the studies just described (Folke, 1984), and recovery from shock
    loadings of chlorophenols is rapid (El-Gohary & Nasr, 1984).

    7.2.2  Phytoplankton

        Kuiper & Hantsveit (1984) monitored the response of enclosed
    marine plankton to chlorophenol additions, and determined that
    exposure to chlorophenols affected algal biomass, composition, and
    activity. In the first of 3 studies, 1 mg 4-MCP or 2,4-DCP/litre
    prevented the increase in algal biomass (as chlorophyll) that occurred
    in control enclosures. Large flagellates made up a greater proportion
    of the algal community in 1 mg/litre-treated enclosures compared with
    controls, perhaps because grazing was reduced (section 7.3). Primary
    productivity generally parallelled the dynamics of algal biomass, as
    it was reduced by exposure to 1 mg 4-MCP/litre; however, the addition
    of 1 mg 2,4-DCP/litre did not affect photosynthetic radiolabelled
    dissolved inorganic carbon (DIC) uptake. Results were generally
    similar during the 2 subsequent manipulations, though the magnitude
    and timing of the effects varied.

        In their studies on ponds, Schauerte et al. (1982) observed major
    shifts in the species composition of the phytoplankton following the
    addition of 5 mg 2,4,6-T3CP/litre. The large population of the
    blue-green alga  Chroococcus limneticus was sharply reduced, and the
    diatom  Nitzschia acicularis was eliminated, while the flagellated
    algae  Euglena and  Trachelomonas appeared in large numbers
    following exposure to 2,4,6-T3CP. The dynamics of other
    phytoplankton, which were less abundant, were not discussed.

        Chorophenols were among the toxicants used by Erickson & Hawkins
    (1980), who measured the response of estuarine phytoplankton
    communities to 15 compounds produced during the chlorination of sea
    water. Natural phytoplankton assemblages, pumped from the estuary to
    flow-through aquaria in the laboratory, were insensitive to
    chlorophenol concentrations of 0.5-2 mg/litre. Photosynthetic
    radiolabelled DIC uptake was not depressed by exposure to 2 mg
    2,4,6-T3CP or 4-MCP/litre.

    7.2.3  Zooplankton

        Marine zooplankton were strongly affected by chlorophenol
    additions during field studies in 1500-litre plastic enclosures
    (Kuiper & Hantsveit, 1984). While the zooplankton communities in the
    control enclosures and those treated with 0.1 mg 4-MCP/litre or 0.1 mg
    2,4-DCP/litre displayed similar dynamics, total biomass and production
    in enclosures treated with 1 mg 4-MCP/litre and 1 mg 2,4-DCP/litre
    were reduced relative to controls throughout the first three-quarters
    of the study. All life-history stages of several copepod species were
    similarly affected. Results in subsequent studies were generally
    similar, though the magnitude of the impact varied.

        More severe effects for  Daphnia exposed to 5 mg
    2,4,6-T3CP/litre were reported by Schauerte et al. (1982) during
    studies on a pond. From initial levels of more than 20 individuals per
    100 ml before the toxicant was added,  Daphnia was eliminated from
    T3CP-treated enclosures in 3 days. The abundance of  Daphnia in
    control enclosures was high and stable during the 24 days of the

    7.2.4  Fish

        There are no controlled field studies on the effects of
    chlorophenols on fish, but fish kills have occurred as a result of
    chlorophenol spills. Mackenzie et al. (1975) compiled information on
    such incidents in British Columbia salmon waters during 1960-73. In
    one instance, an over- flow from a lumber-treatment tank released both
    T4CP and PCP into the Mamquam Channel in 1973, killing an estimated
    500 adult and juvenile coho salmon.

        Chlorophenols may also impair the flavour of fish, even when
    present in the minute quantities detected in moderately-contaminated
    natural waters (section 7.1.3). Chatterjee (1974) reported that kraft
    and groundwood pulp discharges into Lakes Superior and Huron, which
    included phenolic compounds, were apparently responsible for the
    tainting of flesh from fish captured nearby.

    7.2.5  Effects on physical and chemical variables

        The only instance in which chlorophenols affected physical or
    chemical factors in the environment apparently involved a secondary
    effect. In studies in which 5 mg 2,4,6-T3CP/litre was added to
    enclosures in a pond, oxygen levels declined from initial levels of
    3-4 mg/litre to less than 1 mg/litre, within 6 days of treatment, as
    the balance between heterotrophic and autotrophic metabolism shifted
    (Schauerte et al., 1982). Apart from this secondary effect, physical
    and chemical variables appear insensitive to CP additions. Schauerte
    et al. (1982) did not find any significant differences in temperature,
    pH, hardness, sulfide, carbonate, or chloride levels between control
    and 2,4,6-T3CP-treated enclosures. Similarly, levels of phosphate,
    ammonia, nitrate, nitrite, silicate, and pH were unaffected by
    additions of as much as 1 mg 4-MCP or 2,4-DCP/litre (Kuiper &
    Hantsveit, 1984).

    7.3  Treatment Levels

        Unfortunately, the effects of chlorophenols at the low (mg/litre)
    levels that characterize the aquatic environment at large (section
    5.1.2) were not examined in most of these studies. As a result, they
    shed little light on the possible hazards presented by the widespread
    low-level contamination observed in most environments. The microcosm
    study by Virtanen & Hattula (1982) was an exception in this regard.
    However, the mg/litre concentrations used by most research workers are
    relevant to major accidental spills of chlorophenols in the


    8.1  Acute Studies

        In general, the toxicity of chlorophenols increases with an
    increase in the chlorination of the phenol molecule. A convulsant
    effect is associated with the less-chlorinated phenols and oxidative
    phosphorylation uncoupling is more prominent with the highly
    substituted compounds (Ahlborg & Thunberg, 1980; Jones, 1981; Exon,

        Farquharson et al. (1958) studied the effects of a series of
    chlorophenols on male albino rats (Table 17). Symptoms associated with
    the lethal intraperitoneal injection of the monochlorophenols, 2,6-DCP
    and 2,4,6-T3CP, as well as phenol, included an initial increase in
    physical activity (rapid running, nose rubbing) followed by tremors,
    convulsions, and loss of righting reflex. With 2,3,6-T3CP, rats
    suffered convulsions only when handled, and otherwise lay prostrate
    with hypotonia. Hypotonia, starting at the hind limbs, was observed
    within 2-3 min of injection with 2,4-DCP, 2,3,6-, 3,4,5- and
    2,4,5-T3CP, T4CP, and PCP. Body temperature was slightly reduced by
    phenol, MCPs and DCPs, while T3CP caused a slight elevation and T4CP
    and PCP a marked rise in temperature (4-4.5C). Respiratory rate
    increased initially then declined as coma developed, especially with
    T4CP and PCP. The extremities were cyanosed and asphyxial spasms
    occurred about 30 seconds before death. With T4CP and PCP,
    respiration stopped usually one-half to 2 min before cessation of the
    heart, whereas with the other chlorophenols, respiration ceased
    concomitantly with the heart or just before.

        Animal studies indicate that most mono-, di-, and tri-
    chlorophenols are moderately toxic when administered orally, with
    LD50 values ranging between 230 and 4000 mg/kg body weight
    (Table 18). In general, the less-chlorinated phenols have an acute
    oral toxicity very close to that of phenol. T4CP is considerably more
    acutely toxic, with LD50 values of between 100 and 400 mg/kg body
    weight (Ahlborg & Thunberg, 1980; Hattula et al., 1981a). Thus, the
    data indicate that the general order of decreasing acute toxicity is:
    T4CP, MCP, DCP, T3CP.

        The subcutaneous and intraperitoneal routes of exposure have also
    been investigated (Table 18). As with oral administration,
    subcutaneous injections revealed a general order of decreasing acute
    toxicity of: T4CP, MCP, DCP, T3CP.

        Table 17.  Effect of lethal chlorophenol doses given intraperitoneally to ratsa

    Compound                Convulsant      Hypotonia       Max.          Respiration     Rigor mortis
                                            onset (min)     change                        onset (min)
                            activity                        in temp.

    Ether                                                                                 50

      2(o)                  +                  -b            -2.0             -d          > 5.2 < 50
      3(m)                  +                  -b            -2.5             -d          > 5.2 < 50
      4(p)                  +                  -b            -2.5             -d          > 5.2 < 50


      2,4-                  (occasional        2-3c          -0.5             -d          > 5.2 < 50
      2,6-                  +                  -b            -0.7             -d          > 5.2 < 50

      3,4,5-                -                  2-3           + 0.5            -d          < 5
      2,4,5-                -                  2-3           + 0.5            -d          < 5
      2,4,6-                +                                + 0.5            -d          < 5
      2,3,6-                (sometimes         2-3           + 0.5                        < 5

    Table 17.  (cont'd).

    Compound                Convulsant      Hypotonia       Max.          Respiration     Rigor mortis
                                            onset (min)     change                        onset (min)
                            activity                        in temp.

      2,3,4,6-              -                  2-3           + 4.0            -e          < 6

      2,3,4,5,6-            -                  2-3           + 4.5            -e          < 5

    a  From Farquharson et al. (1958).
    b  Apparent after convulsions have lessened.
    c  Muscle twitches evoked by auditory and mechanical stimuli.
    d  Initial increase, then decrease as coma developed; asphyxial spasms 30
       seconds before death; ceases just before or simultaneously with cardiac arrest.
    e  Ceases 1/2 to 2 min before stopping of heart.

    Table 18.  Acute toxicity (LD50s) of phenols and chlorophenols for rats and micea

                                                   RAT                               MOUSE
                              Oral          Subcutaneous   Dermal      IP            Oral                 Subcutaneous   IP

    Phenol                    530-650b      669            250         300           344                  360            -

        -2(o)                 670           950            -           230           347, 345c            -              -
        -3(m)                 570           1390           -           355           521, 530c            -              -
        -4(p)                 261           1030           -           281           1373, 1422c          -              -

        -2,3                  -             -              -           -             2585, 2376c          -              -
        -2,4                  580, 4000d    1730           -           430           1276, 1352c 1600h    -              -
        -2,5                  -             -              -           -             1600, 946c           -              -
        -2,6                  2940          1730           -           390           2198, 2120c          -              -
        -3,4                  -             -              -           -             1685, 2046c          -              -
        -3,5                  -             -              -           -             2643, 2389c          -              -

        -2,3,6                -             -              -           308           -                    -              -
        -2,4,5                820e          2260           -           355           -                    -              -
        -2,4,6                820e          -              -           276           -                    -              -
        -3,4,5                -             -              -           372           -                    -              -

    Table 18 (contd).

                                                  RAT                                MOUSE
                              Oral          Subcutaneous   Dermal      IP            Oral                 Subcutaneous   IP


        -2,3,4,5              -             -              > 2000h     -             400g                 -              97g
        -2,3,4,6              140, 360f     210g           -           130           131g                 120i           82g
        -2,3,5,6                                           > 2000h                   109g                                48g
        -Commercial                                        485-565h    -                                  -              -


        -2,3,4,5              -             -              > 2000h     -             -                    -              -
        -2,3,5,6              -             -              294-469h    -             -                    -              -

    a  Principle database NIOSH (1983). LD50 values given as mg/kg body weight.
    b  Babich & Davis (1981).
    c  Borzelleca et al. (1985a). Data for males presented first, then females.
    d  Kobayashi et al. (1972).
    e  More recent values in US EPA (1979) are 4 times higher (2460-2960 mg/kg).
    f  Hattula et al. (1981a).
    g  Ahlborg & Larsson (1978).
    h  Shen et al. (1983) commercial mixture was primarily 2,3,4,6-T3CP.
    i  Kozak et al. (1979).


        However, in ip injection studies, the toxicities of the mono-,
    di-, and trichlorophenols were comparable while T4CP was 2-3 times
    more toxic.

        The only study available on the acute dermal toxicity of the less
    chlorinated phenols was carried out by Shen et al. (1983). In this
    investigation, Sprague-Dawley rats of both sexes were given 2,3,4,5-,
    2,3,5,6-T4CP, their sodium salts, or a commercial T4CP preparation
    containing over 90% of 2,3,4,6-T4CP and 5-10% of PCP. A very low
    dermal toxicity was reported for 2,3,4,5-T4CP, its phenate salt, and
    2,3,5,6-T4CP, while the sodium salt of 2,3,5,6-T4CP had the highest
    toxicity of all, followed by the commercial T4CP (Table 18). The
    relatively high toxicity of the commercial T4CP could result from its
    content of PCP. The rapid death of the rats (usually 6 h) argues
    against any role being played by the microcontaminants, because the
    PCDDs and PCDFs are usually associated with delayed acute toxicity.

        The effects on animals of these less-chlorinated phenols
    administered via inhalation have not been investigated. However, it
    can be inferred from the one report on the inhalation of sodium-PCP
    (Hoben et al., 1976b) that the toxicity via inhalation would be
    greater than that associated with the oral, intraperitoneal,
    subcutaneous, or dermal routes.

        In their study on the toxicity of 3 different T4CP isomers in
    mice, Ahlborg & Larsson (1978) noted that the LD50 values for all 3
    isomers were lower with ip injection than with oral (gavage)
    administration. This effect of the mode of administration on toxicity
    is apparent in the data on the other chlorophenols (Table 18) and may
    be related to differences in the rates of absorption, metabolism, and
    excretion of these compounds. The low toxicity values obtained with
    subcutaneous injections may be due to a low rate of absorption. The
    vehicle used for administration can also have a significant influence
    on absorption.

    8.2  Skin and Eye Irritation; Sensitization

        Very little information is available on skin and eye irritation or
    sensitization in experimental animals exposed to chlorophenols. Only
    very slight irritation was noted in rabbits following the application
    of dry 2,4,5-T3CP to their skin (McCollister et al., 1961). The
    authors suggested that mild erythema might be caused by high
    concentrations of the material in solution. In a study on the dermal
    toxicity of the T4CP isomers, Shen et al. (1983) found that
    dermatosis occurred in rats painted with 2,3,4,5-T4CP or its phenate
    salt but not with the other 2 isomers or their salts.

    8.3  Short-term Exposure

        All the available information on short-term exposure has been
    obtained by means of oral studies, except for one report concerning
    dermal application. Information is lacking on the effects of
    inhalation and other routes of exposure in experimental animals.

        Exon & Koller (1985) investigated the possible immunological
    effects of 3 chlorophenols on rats exposed both prenatally and
    post-natally. Weanling female rats (3 weeks of age) were given 2-MCP
    (98% pure) (0, 5, 50, or 500 mg/litre), 2,4-DCP (99% pure), or
    2,4,6-T3CP (98% pure); (both at 0, 3, 30, or 300 mg/litre) in the
    drinking-water, for 90 days from weaning through breeding and
    pregnancy. A randomly chosen group of offspring was given the same
    dose regime as the dams for an additional 12-15 weeks after weaning.
    Both groups were observed for another 10 weeks. 2-MCP did not have any
    adverse effects on humoral immunity, cell-mediated immunity, or
    macrophage function in the exposed progeny at any of the exposure
    levels. Exposure of progeny to the highest concentration of 2,4-DCP
    significantly enhanced (P less than 0.05) humoral immune
    responsiveness and decreased cell-mediated immunity in rats with both
    prenatal and postnatal treatments, but not in rats exposed only
     in utero. 2,4,6-T3CP did not have any effects on the immune
    responses tested. Spleen and liver weights were increased in the
    progeny receiving water containing 2,4-DCP or 2,4,6-T3CP at
    300 mg/litre, but not 2-MCP. The authors suggested that this increase
    in organ weight was due to hyperplasia, as no histological anomalies
    were observed.

        Exon & Koller (1985) also monitored haematological parameters and
    organ weights in exposed rat progeny. Combined pre- and postnatal
    (24 months) exposure to 500 mg 2-MCP/litre or 300 mg 2,4-DCP/litre
    significantly elevated red blood cell counts, haemoglobin
    concentrations, and packed cell volumes of offspring. Each of the 3
    compounds was also fetotoxic (section 8.5).

        In studies by Kobayashi et al. (1972), 2,4-DCP in the diet at the
    maximum dose of 230 mg/kg body weight per day, over a 6-month period,
    caused swelling of the hepatocytes in male mice but did not
    substantially affect liver, kidney, spleen, or adrenal histology.
    Furthermore, no significant exposure-related changes were observed in
    organ weight, body weight, food consumption, serum concentrations of
    liver enzymes, or numbers of red and white blood cells.

        In a 90-day study, Borzelleca et al. (1985b) exposed mice of both
    sexes to 2,4-DCP in their drinking-water at mean daily doses of 40,
    114, or 383 mg/kg body weight for males, and 50,143, or 491 mg/kg body
    weight for females. These dosages were calculated from daily water
    consumption data and the concentrations added to the drinking-water.
    At the end of the study period, there were no significant
    treatment-related differences in organ weights, electrolyte levels,
    haematological factors, or the activities of hepatic mixed-function
    oxidases (MFO) or serum enzymes.

        In short-term studies that were preliminary to a carcinogenicity
    bioassay (section 8.6), rats and mice of both sexes were fed diets
    containing 2500-40 000 mg 2,4-DCP/kg for 13 weeks (NTP, 1988). All
    animals survived to the end of the study, except the mice receiving
    the highest dose, all of which died. Male mice and rats of both sexes
    receiving the 20 000 mg/kg diet showed reduced final mean body
    weights. Dose-related effects were apparent in the form of bone-marrow
    atrophy in rats and liver damage (necrosis, multi-nucleated
    hepatocytes) in mice.

        A study on the short-term exposure of rats and rabbits to
    2,4,5-T3CP was carried out by McCollister et al. (1961). Rabbits,
    given 20 oral doses of 500 mg/kg body weight over a 28-day period,
    showed only "very slight kidney and liver changes". In rats receiving
    18 doses of 1000 mg/kg body weight over a 24-day period, there was a
    slight increase in kidney weight, while growth, mortality,
    haematological parameters, and the histology of the lung, heart,
    liver, kidney, spleen, adrenal, pancreas, and testis were unaffected.

        In the same report, male and female rats given a diet containing
    0, 0.1, 0.3, or 1.0 g 2,4,5-T3CP/kg for 98 days did not exhibit
    behavioural changes, increased mortality, changes in food consumption,
    growth, or histology (McCollister et al., 1961). At the 10 g/kg level,
    an increase in the frequency of day-time urination was noted in both
    males and females, as well as significant growth retardation in
    females. Kidney and liver degeneration, which was judged reversible,
    was also found at this exposure level.

        During the course of a study on reproduction (section 8.5.1),
    Blackburn et al. (1986) dosed rats for 5 days per week (males, 11
    weeks; females, 2 weeks and through gestation) by gavage with 0, 100,
    500 or 1000 mg 2,4,6-T3CP/kg body weight in corn oil. A number of
    rats from the 1000 mg/kg group died as a result of treatment (males, 8
    out of 25; females, 3 out of 40). Males and females in this group
    exhibited significant but transitory weight loss compared with
    controls. Male kidney, liver, lung, adrenal, spleen, heart, testis,
    prostate, seminal vesicle, and epididymis weights were unaffected by
    all levels of 2,4,6-T3CP exposure. Females dosed at 1000 mg/kg body
    weight lost hair, were lethargic, and breathed irregularly.

        In a range-finding study, rats and mice of both sexes were exposed
    to 2,4,6-T3CP for 7 weeks to determine the maximum tolerated dose
    (NCI, 1979). The compound was given in the feed up to a maximum level
    of 46 000 mg/kg for rats and 31 500 mg/kg for mice. Weight gain was
    reduced in both male and female rats at all exposure levels, but only
    at the 2 highest dose levels (21 500 and 31 500 mg/kg) in mice. At the
    highest dose, a moderate to marked increase in splenic haematopoeisis
    was found in the rats and midzonal vacuolation of hepatocytes was seen
    in 2 males. All tissues in the mice were normal at the end of 7 weeks.

        Hattula et al. (1981a) dosed rats by garage daily with 0, 10, 50,
    or 100 mg 2,3,4,6-T4CP/kg body weight in olive oil for 55 days.
    Histological changes were found only in the liver, even though the
    kidneys and spleen contained higher concentrations of 2,3,4,6-T4CP.
    This finding suggests that 2,3,4,6-T4CP has a specific effect on the
    liver of rats.

    8.4  Long-Term Exposure

        Investigations of the effects of long-term exposure to
    chlorophenols have been designed primarily to test their carcinogenic
    properties and are described in section 8.7.

    8.5  Reproduction, Embryotoxicity, and Teratogenicity

        Exon & Koller (1981, 1983) and Exon et al. (1984) examined the
    effects of 2-MCP (98% pure; 0, 5, 50, or 500 mg/litre), 2,4-DCP (99%
    pure; 0, 3, 30, or 300 mg/litre), and 2,4,6- T3CP (98% pure; 0, 3,
    30, or 300 mg/litre) on reproductive parameters in mice exposed via
    drinking-water (section 8.3). Females were exposed from 3 weeks of age
    until breeding at 90 days, and through-out gestation to parturition.
    Reanalysis of their original data (Exon & Koller, 1985) led the
    authors to conclude that there was a weakly significant (P less than
    0.1) effect of 2-MCP at 500 mg/litre and 2,4-DCP and 2,4,6-T3CP at
    300 mg/litre, expressed as reduced litter size. The percentage of
    stillborn offspring compared with controls tended to increase in all
    exposed groups. However, the differences were not significant at P
    less than 0.05.

        In mice, sperm motility and penetration of ova were not affected
    by acute (0.1 to 1 mmol/litre) and long-term exposure (90 days at
    50-500 mg/kg body weight per day) to 2,4-DCP (Seyler et al., 1984).
     In vitro penetration was depressed by 2,5-, 3,4-, or 3,5-DCP at
    1 mmol/litre, and it appeared that this concentration of 3,4- or
    3,5-DCP also disrupted the sperm acrosome.

        The effects of oral dosing with 2,4,6-T3CP on rat reproduction
    were investigated by Blackburn et al. (1986). Male rats were given 0,
    100, 500, or 1000 mg 2,4,6-T3CP/kg body weight in corn oil, by
    gavage, 5 days per week, for 11 weeks.

        These exposures to T3CP did not significantly affect male sexual
    behaviour (mount and ejaculation latencies, number of mounts and
    intromissions), plasma-testosterone levels, or sperm counts, motility,
    or morphology. Males from the control and 1000 mg/kg groups were then
    mated with unexposed females, which were sacrificed on day 18 of
    gestation. The exposure regime of the males did not significantly
    affect litter size, sex ratio, mean pup weight by sex, number of dead
    fetuses, or the numbers of resorptions or implantation sites. As part
    of the same study, female rats were dosed in the same manner as the
    males for 5 days per week over 2 weeks and then mated, after which
    dosing continued until day 21 of gestation. No treatment-related
    effects were evident in the breeding success, mean litter size, or
    offspring survival of these females. Litter weights were initially
    significantly reduced in the 500 and 1000 mg/kg body weight groups,
    but this difference had disappeared at 4 days postpartum. This effect
    was suggested to have been a secondary manifestation of female
    toxicity (section 8.2), or of initial differences in litter size
    between treatments.

        In a teratogenicity study of 2,4,5-trichlorophenoxyacetic acid
    (Neubert & Dillman, 1972), 2,4,5-T3CP was also tested, but only at
    doses of 0.9 or 9 mg/kg body weight per day. A slight increase in
    embryo mortality was observed at the higher dose, but its significance
    is unclear. No teratogenic effects were observed.

        Schwetz et al. (1974) studied the embryotoxic and fetotoxic
    effects on rats of purified (99.6%) 2,3,4,6-T4CP and commercial grade
    2,3,4,6-T4CP (73% T4CP + 27% PCP plus 100 ppm total of each of
    dioxins and dibenzofurans). Doses of 10 and 30 mg/kg were given by
    gavage to pregnant rats from day 6 to day 15 of gestation, after which
    they were sacrificed on day 21. A delay in ossification of the skull
    bones was found. Neither of the compounds was embryolethal (evidenced
    by no increase in resorptions or abortions) even at the high dose of
    30 mg/kg per day. No differences were observed in the toxicity of the
    2 grades of T4CP.

        Chlorinated phenols do not appear to be teratogenic for
    experimental animals. Of the compounds tested, levels as high as
    500 mg 2-MCP/litre in drinking-water (Exon & Koller, 1981), 300 mg
    2,4-DCP/litre in drinking-water (Exon et al., 1984), 1000 mg
    2,4,6-T3CP/kg body weight (Blackburn et al., 1986), and 30 mg
    2,3,4,6-T4CP/kg body weight (Schwetz et al. 1974) did not produce any
    teratogenic effects in rats.

    8.6  Mutagenicity and Related End-Points

        Rasanen et al. (1977) found that all dichlorophenol isomers, 4 out
    of 6 trichlorophenols, and 2,3,4,6-T4CP were negative in  Salmonella
     typhimurium mutagenicity bioassays. Similarly, Haworth et al. (1983)
    reported that 2,3-, 2,4-, 2,5-, 2,6-, 3,4-, 3,5-DCPs and 2,4,5- and
    2,4,6-T3CP were negative in  S. typhimurium TA 98, 100, 1535 and
    1537 strains. Nestmann et al. (1980) reported similar findings for
    2,6-DCP and 2,4,5-T3CP. It was reported by Kinae et al. (1981) that
    2,4,6-T3CP was negative in  S. typhimurium TA 98, 100, and 1537
    strains, with and without exogenous metabolic activation, but positive
    in a  B. subtilis recombination assay. At a concentration of
    400 mg/litre, purified 2,4,6-T3CP caused a weak but significant
    increase in the frequency of forward mutations, but did not affect
    intergenic or intragenic re-combinations in the yeast  Saccharomyces
     cervisiae MP-1 strain (Fahrig et al. 1978).

        In mutagenicity studies conducted to supplement a carcinogenicity
    bioassay (NTP, 1988), 2,4-DCP did not produce any revertant colonies
    in  S. typhimurium strains TA 98, 100, or 1537 and yielded equivocal
    results with TA 1535 only in the presence of hamster S9 activation. In
    the mouse L5178Y assay (without metabolic activation),
    trifluorothymidine resistance was increased by 2,4-DCP exposure. In
    the same study,  in vitro exposure of Chinese hamster ovary cells to
    2,4-DCP increased the frequency of sister chromatid exchanges, but did
    not cause chromosomal aberrations.

        Hattula & Knuutinen (1985) showed that purified 2,4,6- T3CP and
    2,3,4,6-T4CP were weakly mutagenic in V-79 Chinese hamster cells
     in vitro, in the absence of metabolic activation by hepatocyte
    co-cultures. They were both non-mutagenic in the presence of metabolic
    activation by hepatocyte co-cultures. 2,6-DCP and PCP were negative
    regardless of the presence of metabolic activators, and 2,4,6-T3CP
    did not induce chromosomal aberrations or sister chromatid exchanges
    in cultures of Chinese hamster ovary cells (Galloway et al., 1987).

        Only very few data are available from  in vivo studies, and these
    are limited to the mouse spot test (Fahrig et al., 1978). Pregnant
    mice were injected intraperitoneally with 50 or 100 mg purified
    2,4,6-T3CP/kg body weight on day 10 of gestation. Examination of
    offspring revealed an increased frequency of coat spots (0.6% in the
    50 mg/kg group versus 0.1% in controls), indicative of a weak
    mutagenic response.

    8.7  Carcinogenicity

        Both 2,4,6-T3CP and 2,4-DCP have been tested for carcinogenicity
    in a 2-year bioassay. The other lower chlorophenols have not been
    adequately tested for their carcinogenic properties.

        A 2-year carcinogenicity study on 2,4-DCP was recently completed
    under the US National Toxicology Program (NTP, 1988). Test animals fed
    diets containing 2,4-DCP (more than 99% pure) received the following
    average calculated doses (mg/kg body weight):


                        F344/N rats              B6C3F1 mice
         Male           Female    Male           Female

         Low dose       210       120            800       430
         High dose      440       250            1300      820

        Mean body weights were reduced, usually by several percent, in all
    of the high-dose groups, as well as the low-dose groups of female
    mice. Mean food consumption was reduced in all treated groups, by
    several percent in rats, and in a dose-related manner in mice (up to
    22%). No significant differences in the survival of any treated group
    occurred. There were dose-related increases in the incidence of
    multinucleated hepatocytes in male mice. No compound-related increases
    in the incidence of neoplastic lesions were observed; in fact, these
    were reduced for mononuclear cell leukaemia in male rats (both doses)
    and malignant lymphomas in female mice (high dose only).

        Innes et al. (1969) tested 120 pesticides and industrial chemicals
    for tumorigenicity in male and female mice. The individual compounds
    were administered at a maximum tolerated dose, by stomach tube, from 7
    days of age to 4 weeks old, and then in the diet at approximately the
    same dosage. The 100 mg/kg daily dose of Omal or Dowicide 2S
    (2,4,6-T3CP) increased tumour incidence in the treated animals at the
    end of 72 weeks. The authors recommended additional statistical
    evaluation and/or studies before a meaningful interpretation could be

        A long-term oral exposure study was carried out on rats and mice
    to test the carcinogenicity of 2,4,6-T3CP (NCI, 1979). Male and
    female F344 rats were given dose levels of 2,4,6-T3CP of 5000 and
    10 000 mg/kg in the feed for 106 weeks. Male B6C3F1 mice were dosed at
    the same levels as the rats for 105 weeks. Female mice were initially
    given dietary levels of 10 000 and 20 000 mg/kg for 38 weeks, which
    were then reduced to 2500 and 5000 mg/kg, respectively, for the
    remaining 67 weeks of the study, because they showed a marked
    reduction in weight gain. At the end of the study, the treated male
    rats showed a significantly higher incidence of malignant lymphomas
    and leukaemias. Leukocytosis and monocytosis of the peripheral blood
    and hyperplasia of the bone marrow were found in those that did not
    show lymphomas and leukaemias. No lymphomas and/or leukaemias were

    detected in female rats, but leukocytosis and monocytosis of
    peripheral blood and bone-marrow hyperplasia were evident. Both male
    and female mice displayed a dose-related statistically significant
    incidence of both hepatocellular carcinomas and adenomas. It was
    concluded that 2,4,6-T3CP was carcinogenic for male Fisher rats and
    both sexes of B6C3F1 mice under the assay conditions used.

        Boutwell & Bosch (1959) studied the tumour-promoting action of 2-
    and 3-MCP, 2,4-DCP, 2,4,5-T3CP, and 2,4,6- T3CP in mice following
    the dermal application of 9,10- dimethyl-l,2-benzanthracene (DMBA)
    (25 l of 0.3% DMBA in benzene) as an initiator. One week after a
    single exposure to DMBA, twice weekly applications of 25 l of a 20%
    solution of the test compound in benzene were made for 12-24 weeks.
    The control group received the pre-treatment dose of DMBA only. The
    authors reported that the monochlorophenols, 2,4- DCP, and 2,4,5-T3CP
    all had a tumour-promoting action similar to that of phenol, while
    2,4,6-T3CP did not have any effect on tumour promotion.

        Exon & Koller (1981,1985) carried out 15 to 24-month studies on
    the effects of pre- and postnatal exposure of rats to 2-MCP and
    2,4-DCP. No evidence of tumour initiation was revealed with exposure
    to 2-MCP (98% pure) at 500 mg/litre drinking-water, or to 2,4-DCP
    (99% pure) at 300 mg/litre drinking-water (Exon & Koller, 1985).
    However, 2-MCP acted as a promoter of the carcinogenic activity of
    ethylnitrosoures (ENU), reducing tumour latency and increasing tumour
    incidence in male rats exposed both pre- and postnatally, compared
    with controls receiving only ENU.

        There is sufficient evidence of the carcinogenicity for animals of
    2,3,7,8-TCDD (IARC, 1987) and a mixture of two H6CDD isomers (NCI,
    1979), which may be present as microimpurities in some technical

    8.8  Factors Modifying Toxicity Metabolism

        Any factor that can interfere with sulfate and/or glucuronide
    conjugation would modify the toxicity of a chlorophenol by inhibiting
    chlorophenol detoxification. Somani et al. (1984) demonstrated with an
    isolated liver-perfusion system that the glucuronide conjugation of
    14C-2,4-DCP can be blocked by galactosamine in the rat. In high
    enough concentrations, galactosamine or similar compounds would
    prolong the residence time in the body and thus the toxicity of the
    chlorophenol molecule.

        In some instances, metabolism of chlorophenol yields molecules
    that are more, rather than less, toxic than the parent molecule. For
    example, when injected into rats intraperitoneally, tetrachloro-
     p-hydroquinone, a metabolite of 2,3,5,6-T4CP, is much more toxic
    than the parent compound (Ahlborg & Larsson, 1978).

        The toxicology of chlorophenols is further complicated by
    micro-contaminants in technical grade products, particularly in the
    higher chlorinated compounds. Some of these impurities are themselves
    extremely toxic. Conversely, microcontaminants are known to induce
    enzymes that can affect the rate of chlorophenol metabolism and
    excretion (Ahlborg & Thunberg, 1978). For these reasons, assessment of
    toxicity studies with chlorophenols requires a knowledge of the types,
    levels, and toxicology of the contaminants present. This is
    particularly true when extrapolating animal studies (which often
    involve the use of purified compounds) to human beings, who are
    generally exposed to technical formulations. The residue
    concentrations and toxicology of the dibenzodioxin and dibenzofuran
    microcontaminants have been reviewed by WHO (in press).

    8.9  Mechanisms of Toxicity, Mode of Action

        The major mode of action of chlorophenols appears to be the
    uncoupling of oxidative phosphorylation. The strength of the
    uncoupling effect is related to the degree of chlorination: PCP is the
    strongest inhibitor of oxidative phosphorylation, MCP the weakest
    (Farquharson et al., 1958; Mitsuda et al., 1963; Weinbach & Garbus,
    1965; Carlson, 1978). To a lesser extent, inhibition of oxidative
    phosphorylation is affected by the positions of the chlorine atoms on
    the molecule. There appears to be a relationship between chlorination
    and the toxicity of PCP and T4CP (Table 18), although there is no
    clear-cut relationship between the degree of chlorination and
    toxicityin MCP, DCP, and the T3CP series. PCP and to a lesser extent
    other chlorophenols, depending on their degree of chlorination, have
    been shown to bind strongly to mitochondrial protein (Weinbach &
    Garbus, 1965). At low levels, PCP uncouples oxidative phosphorylation,
    at intermediate levels, it inhibits the formation of high-energy
    intermediates in the phosphorylation system and, at high
    concentrations, it inhibits the electron transport system (Mitsuda et
    al., 1963). PCP has been shown to bind directly to mitochondrial
    ATPase (Stockdale & Selwyn, 1971). Inhibition of ATPase would prevent
    the breakdown of ATP to ADP and energy release to the mitochondria. In
    response to the reduced availability of energy, a compensatory
    increase in catabolism would be expected. Increased catabolism would
    result in higher rates of oxygen consumption and, under short-term
    exposure conditions, depletion of metabolic stores. With oxidative
    phosphorylation uncoupled, the energy provided by catabolism would be
    released as heat. This process would underlie, respectively, the
    elevated respiratory rate and body temperature, and the long-term
    weight loss observed in intoxicated organisms (Weinbach, 1957;
    Farquharson et al., 1958; Mitsuda et al., 1963; Wood et al., 1983).
    Similarly, Exon & Koller (1985) suggested that the immune effects of

    2,4-DCP might result from the uncoupling of oxidative phosphorylation,
    thus impairing cellular energy production in immunocompetent cells, or
    perhaps, from a direct toxic effect on subpopulations of cells
    involved in immune responses. The uncoupling of phosphorylation
    appears to be due to the chlorophenate ion, while the convulsant
    action is caused by the undissociated molecule (Farquharson et al.,

        Chlorophenol toxicity may also result from a more general
    inhibition of enzyme activity by these compounds. Arrhenius et al.
    (1977) demonstrated that, in rat liver microsomal preparations,
    purified chlorophenols selectively inhibited cytochrome P-450 activity
    at the terminal oxygenation step of the MFO enzyme system by
    interfering with the coupling of flavin to this enzyme. 2,4-DCP,
    2,4,6-T3CP, and 2,3,4,6-T4CP concentrations of 0.3 mmol-3 mmol/litre
    showed a weaker inhibition of C-oxygenation than PCP. Kaneki & Tanaka
    (1984) reported that the inhibition of porcine lipase activity and, to
    a lesser extent, wheat germ lipase activity increased with the number
    of chlorine atoms on the phenol ring. The inhibiting action of PCP was
    greater than that of 2,3,4,6-T4CP, which in turn was stronger than
    2,3,6- T3CP, while DCP and MCP did not have any effect. Carlson
    (1978) found that certain T3CP isomers inhibited glucuronyl
    transferase activity and EPN detoxification  in vitro, but not
     in vivo. The reason for these effects could be the absence from the
     in vitro preparations of binding proteins or alternate metabolic
    enzyme systems (Somani et al., 1984).

        The mechanisms of carcinogenicity or co-carcinogenicity of
    chlorophenols (section 8.7) remain unresolved at present. Exon &
    Koller (1985) suggested that chlorophenols may play a role in
    carcinogenicity by altering the toxicity of carcinogens (by inhibiting
    detoxifying enzymes, damaging DNA, or altering DNA repair) or by
    reducing immunosurveillance. It has been shown by Vizethun & Goerz
    (1979) that 2,4,5-T3CP and PCP can induce different species of
    cytochrome P-450 in nuclei and microsomes. The importance of this
    finding in relation to carcinogenesis is as yet unclear, but nuclear
    monoxygenases could play a critical role in cell alterations, because
    of their proximity to DNA and their ability to induce binding of
    electrophilic compounds.


        As a result of the diverse range of applications of chlorophenols
    (section 3.2.2), there is considerable potential for human exposure to
    these compounds and their associated contaminants. Knowledge
    concerning the toxic effects of chlorophenols on people is based
    primarily on studies on persons employed in the chemical-manufacturing
    industry, where mainly DCP and T3CP are involved, and the
    wood-preservation/ protection industries, where T3CP, T4CP, and PCP
    are the major forms used (see reviews by Behrbohm, 1959, Kozak et al,
    1979, and Ahlborg & Thunberg, 1980). Reports of chlorophenol toxicity
    in the general population are few in number, though chlorophenol
    contamination of human tissues and fluids seems widespread (sections
    5.2, 5.3).

    9.1  Acute Toxicity

        Accidental and suicidal poisonings with commercial chlorinated
    phenols have been reported (WHO, 1987b), and a number of the most
    heavy acute exposures have resulted in death. With the support of
    animal studies, the signs and symptoms of acute exposure to
    chlorinated phenols include: convulsions (especially with
    less-chlorinated phenols), ataxia, mental and physical fatigue,
    headache, dizziness, disorientation, tachycardia, body temperature
    change (decreased with monochlorophenols, increased with,
    particularly, tetrachlorophenols and pentachlorophenol), and increased
    sweating. Cyanosis and asphyxia spasms shortly precede death. Death is
    apparently due to cardiac arrest and is followed, at least in animals,
    by rapid rigor mortis, especially with T3CP and T4CP poisoning.

        In general, the acute toxicity of chlorophenols in animals
    increases with the number of chlorine atoms in the molecule (section
    7.1.1). In man, the only published estimate of a minimum lethal oral
    dose (LDLo) for any chlorophenol is for PCP (29 mg/kg body weight,
    approximately 2 g for an average person) (WHO, 1987b). The human LDLo
    for unchlorinated phenol is estimated to be 140 mg/kg body weight.

        Acute exposure of human beings to lower chlorophenols has also
    occurred as a result of industrial accidents during the production of
    2,4,5-T3CP and has been most consistently associated with chloracne
    (a persistent form of acne with keratotic follicles associated with
    exposure to chlorinated compounds) and symptoms of liver toxicity.

        For example, in April 1968, an explosion in a reactor producing
    2,4,5-T3CP at a manufacturing plant in England released a
    considerable amount of 2,4,5-T3CP and TCDD, exposing 14 people inside
    the plant (May, 1973). Abnormalities in liver function tests (elevated
    thymol turbidity, zinc turbidity), serum-transaminases, and urine
    analyses were detected immediately after the incident; 10 days later,

    the same tests gave normal values. Plant activity resumed but, by
    December, 79 cases of chloracne were reported, some of whom also
    suffered from conjunctivitis. The entire building was then thoroughly
    cleaned, the interior walls resurfaced, and contaminated equipment was
    buried. In a follow-up study conducted 10 years after the accident,
    the frequencies of chromosomal aberrations and sister chromatid
    exchange rates in lymphocyte cultures from exposed subjects were
    normal (Blank et al., 1983).

        To date, acute exposure of the general population to lower
    chlorinated chlorophenols has been documented only from the ICMESA
    plant accident in Seveso, Italy. An over-heated chemical reactor
    discharged a cloud containing sodium hydroxide, Na-T3CP, and TCDD
    into the atmosphere, contaminating an area south of the factory
    containing 37 000 people (Hay, 1976; Del Como et al., 1982). Within 2
    weeks of the accident, toxic effects were being treated in some 500
    people (Hay, 1976). The most prevalent signs of exposure were skin
    burns and chloracne, which was evident in 193 of the inhabitants. The
    highest soil concentrations of 2,3,7,8-TCDD were associated with the
    most severe cases of chloracne (Caramaschi et al., 1982). An
    international steering group formed by the Italian government stated
    in their final 1984 document that, with the exception of chloracne, no
    clear health effects remained in the 193 persons in Seveso who were
    registered as having chloracne, 20 of whom still showed symptoms in
    1984. Exposed children had indications of increased enzyme activities
    (increased D-glucaric acid in the urine) up to 3 years after exposure
    (WHO, in press).

    9.2  Long-term Exposure

    9.2.1  Effects on skin and mucous membranes

        Workers may display a variety of overt symptoms of chlorophenol
    exposure. Persons often complain of irritations of the skin, mucous
    membranes and respiratory tract as a result of direct airborne
    contact. In addition, chronic skin ailments, particularly chloracne,
    but also other skin lesions, ulcerations, and porphyria cutanea tarda
    have been reported, mainly from plants manufacturing chlorophenols for
    phenoxy-acetic acid herbicides. Clinical indications of liver damage
    and haematological and neurological effects have also been reported,
    particularly in association with high exposures.

        For instance, among workers in a 2,4-DCP and 2,4,5-T3CP
    manufacturing plant in the USA, 29 cases of chloracne and 11 cases of
    porphyria were detected (Bleiberg et al., 1964). In addition to the
    two chlorophenols, PCDDs and PCDFs, acetic acid, phenol,
    monochloroacetic acid, and sodium hydroxide may have contributed to
    the symptoms of the workers. Poland et al. (1971) examined employees
    from the same plant 6 years after the report of Bleiberg et al.

    (1964). Of the 73 male workers examined, 48 (66%) had some degree of
    acne, and chloracne was found in 13 workers (18%). The severity of the
    chloracne was not correlated with job location within the plant or
    duration of employment, suggesting that there is a large variation in
    the susceptibility of individuals to exposure to chlorophenols or
    their contaminants.

        Workers exposed to 2,4,5-T3CP in a production plant in the USSR
    also developed dermatitis, as reported by Kozak et al. (1979).
    Similarly, an incident of acute dermatitis in Russian agricultural
    workers exposed to copper trichlorophenate was reported (Kozak et al,

        Ott et al. (1980) examined the effects of exposure to commercial
    2,4,5-T3CP and 2,4,5-T at a plant in the USA. In unacclimated
    personnel, levels of less than 4 mg T3CP/m3 and/or 0.1 mg
    2,4,5-T/m3 caused nasal irritation, sneezing, and a bitter taste in
    the mouth. TCDD concentrations in both preparations were less than
    1 mg/kg, in 1966, and 0.1 mg/kg, after 1972. Medical records of 204
    exposed employees over the period 1950-76, did not reveal any cases of
    chloracne or porphyria. The mortality rate of employees was lower than
    expected (6 versus 13.3 expected) in workers exposed for less than 1
    year and close to expected in those exposed for 1 year or more
    (5 versus 7 expected).

        In clinical studies on workers at a 2,4,5-T-manufacturing plant
    (presumably exposed to 2,4,5-T3CP and its microcontaminants),
    exposure was strongly associated with the development of chloracne,
    plus increased prevalences of actinic elastosis and hirsutism (Suskind
    & Hertzberg, 1984).

        Jirasek et al. (1974) and Pazelerova et al. (1974) reported the
    cases of about 80 people with both acute (industrial accident) and
    long-term (up to 6 years) exposure to Na-T3CP, tetrachlorobenzene,
    the sodium salt of trlchlorophenoxyacetate, and their contaminants.
    Symptoms developed as long as 18 months after exposure. Chloracne
    appeared in 96% of 55 people examined.

        In lumber-mill workers, lesions and ulcerations were found in skin
    areas in direct contact with a Na-T4CP solution, usually through
    soaked clothing (Stingily, 1940). On the basis of roughly 300-400
    cases, it was concluded that Na-T4CP caused the dermatitis while the
    subsequent chronic lesions and nicerations were caused by fungal

        Kleinman et al. (1986) and Fenske et al. (1987) evaluated the
    extent and impact of occupational exposure to Permatox 100 (20.7%
    2,3,4,6-T4CP, 3.1% PCP, plus substantial quantities of PCDDs and
    PCDFs) in workers from a lumber mill in Washington state. The results
    of their monitoring of air and urine are presented in section 5.3. In
    health effects questionnaires, exposed workers complained
    significantly more frequently than controls of headaches, eye and
    upper respiratory irritations, and unusual sweating, though there was
    no significant correlation between urinary levels and the frequency of
    these symptoms. The effects of exposure to a commercial Na-T4CP
    solution (containing hexa-, hepta-, and oetachlorodibenzo- p-dioxins,
    dibenzofurans, and probably PCP and T3CP) were investigated by
    Sterling et al. (1982) in workers at 2 sawmills in British Columbia,
    Canada. The study included 1014 men with from 1 to over 20 years of
    known exposure, compared with 103 loggers and outdoor municipal
    workers, who served as controls. In self-administered questionnaires,
    exposed workers reported significantly increased incidences of various
    dermatological, upper respiratory, and general respiratory symptoms,
    as well as eye irritation. These disorders were significantly more
    frequent in the high-exposure group (247 workers) than in the workers
    considered to be in the low/moderate-exposure group (767 workers),
    who, in turn, had a higher incidence than the controls.

        A detailed study of chlorophenol exposure in a sawmill in the same
    geographical area was carried out by Embree et al. (1984) (section
    5.3). They divided the workers into a control group from areas with no
    identifiable air contaminants, a group of workers who worked in close
    proximity to recently treated lumber but who did not have manual
    contact (airborne), and a group who were responsible for the manual
    handling of recently treated lumber (dermal plus airborne). Serum and
    urine levels of chlorophenols were related to exposure in a
    dose-dependent manner (section 5.3). From health histories, the only
    symptoms that occurred significantly more frequently in exposed
    workers were a productive cough and a reduced rate of forced
    exhalation in the "airborne" group. These symptoms could not be
    attributed to chlorophenol exposure, as the "dermal-plus-airborne"
    group were exposed to similar atmospheric chlorophenol levels and had
    higher levels of overall exposure, yet recorded a significantly lower
    incidence of productive coughing.

        Alexandersson & Hedenstierna (1982) examined the effects of
    long-term exposure to T3CP vapours in workers at a gas-mask factory.
    Trichlorophenol vapour, because of its characteristic smell, was used
    at the factory for checking leaks in gas masks. Complaints of eye,
    nose, and airway irritation were voiced by 7 individuals who had been
    employed in testing masks for from 2 to 10 or more years. Pulmonary
    function tests revealed that exposed workers displayed reduced forced
    expiratory flow and increased closing volume in the lungs compared
    with controls.

    9.2.2  Systemic effects

        Effects on liver and kidney function and haematological parameters
    have also been investigated in workers exposed to chlorophenols. The
    findings have been generally negative. In studies on Canadian sawmill
    workers (Enarson et al., 1986), serum levels of creatinine, bilirubin,
    glutamic oxaloacetic transaminase, and alkaline phosphatase, and
    patient histories of jaundice, liver, kidney, and heart disease did
    not differ from those of the controls. Blood-leukocyte counts and
    haematocrit decreased, and urine-erythrocyte levels increased
    following chlorophenate exposure. These effects were significant only
    for the haematocrit and haematuria, and only for workers handling
    treated lumber.

        Sterling et al. (1982) reported that chlorophenol-exposed sawmill
    workers filling out self-administered questionnaires reported
    significantly increased incidences of gastrointestinal,
    musculoskeletal, acute systemic, liver, kidney, and neurological

        In the study on industrial workers exposed to di- and
    tri-chlorophenols, Bleiberg et al. (1964) reported elevated
    coproporphyrin excretion in the maintenance men that could have been
    due to more intense, though sporadic, exposure. Hepatotoxic effects
    were not found in the study group.

        Initially, more than one-third of Czechoslovakian 2,4,5-T3CP- and
    2,4,5-T-manufacturing workers described by Jirasek et al. (1974) and
    Pazelerova et al. (1974) showed indications of mild liver damage,
    which, in some instances, was confirmed by needle biopsy. The workers
    had increased serum levels of cholesterol (56%), total lipids (67%),
    and lipid-phosphorus (42%). A small but significant decrease in
    serum-albumin, and an increase in serum-globulin were also found.

    9.2.3  Psychological and neurological effects

        A range of psychological and neurological symptoms have also been
    associated with exposure to chlorophenols, often in association with
    other chemicals. Workers from a plant in the USSR who were
    occupationally exposed to 4-MCP complained of "... sleep disorders
    (usually sleepiness and sometimes insomnia), irritability, frequent
    mood changes, and rapid fatigability" (Gurova, 1964).

        Similarly, Kleu & Goltz (1971) reported that 10 persons suffering
    from chloracne as a result of 15 years' exposure to a T3CP
    formulation complained of "... decreased sexual activity, easy
    fatigability, alcohol intolerance, and loss of interest ... reduced
    vital psychic and intellectual capacities combined with neurasthenia
    and mental depression". The actual occupations of these individuals
    were not stated.

        Gilioli et al. (1983) conducted electroencephalographic analyses
    of workers exposed to T3CP and TCDD at the Seveso plant in Italy,
    site of an accident in 1976. These workers had both long-term, and
    possibly acute high-level exposure to TCDD and T3CP. Exposed workers
    generally exhibited an increased incidence of abnormal EEG tracings,
    which were particularly associated with increased proportions of theta
    waves, and had a slower visual reaction time than a non-exposed group.

        The 2,4,5-T3CP-and 2,4,5-T-manufacturing employees reported by
    Jirasek et al. (1974) and Pazelerova et al. (1974) showed neurological
    abnormalities, including myographic changes in 23% of those tested.
    Neurasthenic symptoms were present in 60% of the workers, compared
    with 30-40% of the general population. Some of the workers complained
    of fatigue, loss of appetite, weight loss, and abdominal pain.

    9.2.4  Reproductive effects

        The effects of chlorophenols on reproduction have been
    investigated in 3 studies. Corddry (1981) provided data on pregnancy
    outcomes in women married to workers from a sawmill in British
    Columbia using Na-T4CP and Na-PCP. Analysis of data from 43 women,
    with a total of 100 pregnancies, did not reveal any significant
    differences in the pregnancy outcomes of women living with exposed men
    compared with those living with unexposed men. A slight trend towards
    more adverse pregnancy outcomes in the exposed group disappeared when
    corrected for alcohol consumption. Male fertility was not studied.

        Suskind & Hertzberg (1984) reported pregnancy outcomes in the
    families of male workers manufacturing 2,4,5-T (and with probable
    exposure to 2,4,5-T3CP and 2,3,7,8-T4CDD) compared with those of
    other males from the same plant. There were no significant differences
    between the families of exposed and non-exposed workers, but the rates
    for stillbirth and death during the first 4 weeks were higher in the
    families of exposed workers.

        The pregnancy outcomes were surveyed in wives of workers from a
    chlorophenol-manufacturing plant in Michigan, USA, potentially exposed
    to PCP, 2,4,5-T3CP, and their microcontaminants for the group as a
    whole (Townsend et al., 1982). There was no significant association
    between exposure to dioxins (these were the focus of the study) and
    adverse pregnancy outcomes. When the conceptions were divided into
    subgroups according to risk factors associated with the mother, a
    subgroup of 9 TCDD-exposed conceptions was identified of which 3 were
    spontaneous abortions.

    9.2.5  Carcinogenicity

        A large number of epidemiological studies have been published
    concerning human cancer outcomes following occupational exposure to
    chlorophenols, phenoxy herbicides (made from and contaminated with
    chlorophenols), and chlorinated dibenzo- p-dioxins and dibenzofurans
    (microcontaminants found in some chlorophenols and phenoxy
    herbicides). Most of these studies have been described and reviewed in
    several publications by the International Agency for Research on
    Cancer (IARC, 1979, 1986, 1987), and readers are referred to the IARC
    monographs for details of individual studies. Only the conclusions of
    these studies are given in this publication with the emphasis on
    studies that specifically concern exposure of populations to
    chlorophenols. Studies that address the effects of exposure to phenoxy
    herbicides in general and MCPA, and do not involve substantial
    concomitant exposure to chlorophenols are not discussed. These
    include: cohort studies on phenoxy herbicide sprayers (Axelson et al.,
    1980; Hogsted & Westerlund, 1980); studies on Vietnam war veterans
    (Royal Commission on the Use and Effects of Chemical Agents on
    Australian Personnel in Vietnam, 1985; Lathrop et al., 1987); and
    workers involved in the manufacture of MCPA (Coggon et al., 1986).
    Case-control studies covering phenoxy herbicide exposure, but with no
    mention of exposure to chlorophenols (Balarajan & Acheson, 1984;
    Greenwald et al., 1984; Kogan & Clapp, 1985; Hoar et al., 1986; Kang
    et al., 1986; Vineis et al., 1987) and data from occupational
    mortality statistics in which exposure data are inferred only from job
    titles are also not included (Milham, 1982, 1985; Callagher &
    Threlfall, 1984).  Case-control studies reviewed by IARC

        Soft tissue sarcoma (STS) was studied in individuals exposed to
    chlorophenols and other chlorophenol-based chemicals in Sweden
    (Hardell & Sandstrom, 1979; Eriksson et al., 1981), New Zealand (Smith
    et al., 1984), and the USA (Woods et al., 1987). Relative risks (RR)
    of STS for exposure to chlorophenols alone were elevated in both of
    the Swedish studies (RR = 6.6; 96% CI, 2.1-20.9; and RR = 3.3; 95%
    CI, 1.3-8.1) and for one potentially exposed subgroup in the New
    Zealand study (RR = 7.2; 90% CI, 1-ND). They were not elevated in the
    US study, unless the subgroup of cases with Scandinavian names
    (RR = 7.2; 95% CI, 2.1-24.7) and the subgroup of lumber graders
    (RR = 2.6, 95% CI, 1.1-6.4) were considered separately. Chlorophenol
    exposures (2,4,6-T3CP, PCP, and others) were poorly described and not
    quantified. Case-control studies of malignant lymphomas (Hodgkins
    disease and non-Hodgkins lymphoma) have also been carried out in
    Sweden (Hardell et al., 1981), New Zealand (Pearce et al., 1986), and

    the USA (Woods et al., 1987). In Sweden, low-grade exposure (up to one
    week continuous or 1 month intermittent) and high-grade exposure
    (greater than the low-grade exposure criteria) to unspecified types of
    chlorophenols resulted in relative risk values of 2.2 (95%
    CI, 1.1-4.6) and 7.6 (95% CI, 3.2-17.7), respectively. In the New
    Zealand study of 83 cases of non-Hodgkins lymphoma, exposures were not
    classified into high or low, and were not quantified; however, some
    cases were not likely to have been exposed to 2,4,6-T3CP and PCP.

        The relative risk for non-Hodgkins lymphoma in pelt department
    workers with potential exposure to 2,4,6- T3CP was 1.9 (90%
    CI, 0.9-4.0); however, other meat workers without exposure to
    chlorophenols had a relative risk of the same order. In the US study,
    the relative risks for non-Hodgkins lymphoma were not elevated for
    groups exposed to low, medium, or high levels of chlorophenols.

        A statistically significant increase in nasal and nasopharyngeal
    cancer was found among workers exposed to chlorophenols (mainly tri-,
    tetra-, and pentachlorophenol) in a Swedish case-control study
    (Hardell et al., 1982). In an inter-Nordic study, 2 cases of sinonasal
    cancer out of 167 were identified as having been exposed to
    chlorophenols (not further specified) compared with 0/167 colorectal
    cancer controls (Hernberg et al., 1983). In a Danish study, no
    association was found between sinonasal cancer and potential exposure
    to chlorophenols, as inferred from employment records (Olsen &
    Moller-Jensen, 1984).

        The results of 2 Swedish studies did not show statistically
    significant associations between primary liver cancer or colon cancer,
    and exposure to chlorophenols (mainly tri-, tetra-, and
    pentachlorophenol) (Hardell, 1981; Hardell et al., 1984).

        No significant associations were found between multiple myeloma
    and potential exposure to chlorophenols (probably mainly
    penta-chlorophenol) in a case-control study carried out in New Zealand
    (Pearce et al., 1986).  Cohort studies reviewed by IARC

        Three follow-up studies have been undertaken on small groups of
    workers exposed to 2,3,7,8-TCDD during accidents in the manufacture of
    2,4,5-T3CP (Cook et al., 1980; Zack & Suskind, 1980; Thiess et al.,
    1982). When combined, these cohort studies show 19 cancer deaths
    observed versus 14.7 expected (RR = 1.29; 95% CI, 0.78-2.02). Two
    studies (Ott et al., 1980; Zack & Galley, 1983) covered workers
    employed in the manufacture of 2,4,5-T from 2,4,5-T3CP. The observed
    cancer deaths versus expected cancer deaths for these cohorts were 1
    versus 3.6 and 35 versus 30.9, respectively.

        A total of 3 deaths from soft-tissue sarcoma (STS) were identified
    in US cohorts studied by Honchar & Halperin (1981). This was
    equivalent to 2.9% of the deaths in the 4 cohorts, where approximately
    only 0.07% would be expected. Later, one additional STS case was
    observed in one of these cohorts (Cook, 1981), and an additional 3
    cases of STS were reported in workers in 2,4,5-T-manufacturing plants
    (Johnson et al., 1981; Moses & Selikoff, 1981). Fingerhut et al.
    (1984) reviewed the histological specimens for the 7 cases reported as
    having STS. In the review, 5 of the 7 cases were diagnosed as having
    STS. A review of the employment records for the 7 patients showed that
    all of them had worked in 2,4,5-T-manufacturing plants; 4 of the
    patients had specific assignments to 2,4,5-T3CP or 2,4,5-T

        A cohort study on workers in 2 Danish chemical plants (Lynge,
    1985), in which 2,4-D and 2,4-DP were produced together with MCPA and
    MCPP, showed the overall cancer incidence to be close to that of the
    Danish population (208 observed cases and 216.5 expected). In men, 5
    cases of STS were observed, where 1.84 were expected. The number of
    malignant lymphoma cases in men was 7, with 5.37 expected cases. In
    the subgroup of men assigned to the phenoxy herbicide-manufacturing
    department, 11 lung cancer cases were observed in men, when 5.33 cases
    were expected.  More recent studies

        A Swedish study on soft-tissue sarcoma and exposure to phenoxy
    acid herbicides and chlorophenols was recently repeated using 55 new
    cases diagnosed in 1978-83 (Hardell & Eriksson, 1988). In addition to
    comparing the cases with controls from the general population, a
    control group of patients with cancers other than malignant lymphoma
    and nasopharyngeal cancer was selected. An elevated relative risk for
    exposure to phenoxy herbicides was found, but no statistically
    significant differences were observed between cases and controls with
    regard exposure to chlorophenols. The relative risk for chlorophenols
    was based on only 4 exposed cases.

        In a case-control study nested within a cohort of Finnish
    woodworkers, no association was found between respiratory cancer and
    exposure to chlorophenols (mainly tetra- and trichlorophenols), but
    this result was based on only 3 exposed cases (Kauppinen et al.,

        In a more recent cohort study on 2192 employees at a plant
    involved in the production of higher chlorophenols and phenoxy acids
    (Cook et al., 1987; Ott et al., 1987), mortality during the period
    1940-82 among workers with potential occupational exposure to
    chlorophenols was similar to that of US white males for all causes and
    for all cancers; there were 81 observed cancer deaths versus 79.3
    expected deaths. No statistically significant excesses of mortality
    were observed for the cancers of a prior interest (nasal and
    nasopharyngeal, stomach, liver, connective and soft tissue,
    lymphomas). Excesses in mortality that did not reach the 5% level of
    probability were reported for stomach cancer (6/3.8) and non-Hodgkins
    lymphoma (5/2.6).

        A cohort of 878 persons, employed in the manufacture of 2,4-D at
    the same plant between 1945 and 1983, was followed up for mortality
    until 1983. Some of these employees may also have been exposed to
    other chlorophenols at the plant site. There were 20 cancer deaths
    against 16.9 expected. There were 5 deaths from lymphatic and
    haematopoietic cancer against 2.5 expected. Two cases had
    lymphosarcoma and reticuiosarcoma, and there was one case of Hodgkins
    disease. Both workers who died from non-Hodgkins lymphoma had had
    potential exposure to PCDDs. Death certificates were reviewed with
    special attention directed to soft-tissue sarcoma, but no cases were
    identified (Bond et al., 1988).


    10.1  Evaluation of Human Health Risks

    10.1.1  Exposure levels  Non-occupational exposure

        Exposure to chlorophenols other than pentachlorophenol may occur
    via ingestion, inhalation, or dermal absorption (section 5.2). The
    general population is thought to be exposed mainly through the
    ingestion of food and drinking-water. These compounds have not been
    quantified in the ambient atmosphere, but atmospheric levels are
    likely to be of the same order of magnitude (ng/m3) as those of PCP.
    Even with 100% absorption, uptake via this route would be much less
    than 1 g/day. Similarly, even though low levels of the lower
    chlorinated phenols occur widespread throughout the environment,
    direct dermal contact with these compounds will not be an important
    route of exposure for the general population. Non-occupational
    exposure (inhalation, dermal) to chlorophenol-treated lumber has not
    been investigated, but may be significant, if chlorophenols are used
    for extensive treatment of the interior of houses. Significant
    exposures may also occur if consumers use chlorophenol-based products
    without appropriate care and protection.

        An estimate of non-occupational exposure through the ingestion of
    drinking-water and food can be made using representative published
    concentrations of the major commercial chlorophenols other than
    pentachlorophenol. The daily exposure of a 60-kg person in Canada to
    2,4-DCP, 2,4,5-T3CP, and 2,3,4,6-T4CP is estimated in Table 19, on
    the basis of assumptions detailed in the table. These calculated
    exposures may be overestimates in that residue determinations are
    generally taken from contaminated areas, and because kinetic or
    metabolic studies usually involve high chlorophenol concentrations. On
    the other hand, estimates have not been made for all foodstuffs; for
    example, no data were found for fruits, dairy products, or nuts.
    Exposure to other chlorophenols, in particular 2,4,6-T3CP, cannot be
    estimated, because there are insufficient data on the concentrations
    present in water and food. Nevertheless, the values calculated should
    suffice as a first approximation of exposure.

        Table 19.  Estimated daily per capita exposure to 2,4-DCP, 2,4,5-T3CP, and 2,3,4,6-T4CP from food and drinking-water in Canada

    Source         Daily                 2,4-DCP                         2,4,5-T3CP                    2,3,4,6-T4CP
                   in Canada      Concentration   Exposure      Concentration    Exposure       Concentration     Exposure
                   (kg)a          (g/kg fresh    (g/kg        (g/kg fresh     (g/kg         (g/kg            (g/kg
                                  weight)         body weight   weight)          body weight    fresh weight)     body weight
                                                  per day)b                      per day)                         per day)

    Tap            1.4            0.093c          0.002         0.035c           0.0008         0.009c            0.0002
    water          (litres)d

    potatoes       0.36           6e              0.036         0.041f           0.0002         1.917g            0.011

    Meat and
    poultry        0.26           5h              0.022         0.034f           0.0002         3i                0.013

    Fish and
    seafood        0.019          13.75j          0.004         0.76k            0.0002         10.3k             0.003

    exposure                                      0.064                          0.0014                           0.027

    Table 19.  (contd).

    Source         Daily                 2,4-DCP                         2,4,5-T3CP                    2,3,4,6-T4CP
                   in Canada      Concentration   Exposure      Concentration    Exposure       Concentration     Exposure
                   (kg)a          (g/kg fresh    (g/kg        (g/kg fresh     (g/kg         (g/kg            (g/kg
                                  weight)         body weight   weight)          body weight    fresh weight)     body weight
                                                  per day)b                      per day)                         per day)

    Tolerable                                     200.0l                         100.0m                           10.0n
    daily intake
    (g/kg body
    weight per

    a  Per capita per day in 1984 (Statistics Canada, 1986).
    b  Based on a 60-kg person.
    c  Jyvaskyla, Finland (Paasivirta et al., 1985).
    d  Water consumption for 60 kg man per day (NHW, 1983).
    e  Average for potatoes treated with 2,4-D (Bristol et al., 1982).
    f  Assuming that the ratio of 2,4-DCP: 2,4,5-T3CP is the same as for 1984 Canadian imports.
    g  Average from Alberta Government assay (Jones, 1981), assuming all T4CP is 2,3,4,6-T4CP.
    h  Muscle concentration from chickens fed 50 mg Nemacide/kg, 7 days post-treatment (Sherman et al., 1972).
    i  Upper concentration detected in chicken flesh from British shops (Farrington & Munday, 1976).
    j  Mean muscle concentration calculated as g/kg wet weight Bacon, (1978).
    k  Mean muscle concentration (Paasivirta et al., 1985).
    l  NOEL taken from Kobayashi et al. (1972) using a 500-fold safety factor.
    m  NOEL taken from McCollister et al. (1961) using a 1000-fold safety factor.
    n  NOEL taken from Schweiz et al. (1974) using a 1000-fold safety factor.


        The daily ingestion of these chlorophenols by a 60-kg person is
    estimated to be 3.84 g of 2,4-DCP; 0.084 g of 2,4,5-T3CP, and
    1.62 g of 2,3,4,6-T4CP (on the basis of data in Table 19 and
    calculated for a 60-kg person). These values are presented on a
    per-unit-weight basis in Table 19. In Canada, the amount of PCP used
    is approximately equal to the amounts of all other chlorophenols
    combined, suggesting that PCP exposure is roughly equal to that of the
    other chlorophenols. Thus, the total estimated exposure of Canadians
    to all chlorophenols including PCP is about 10 g/person per day. This
    value agrees with the 10-30 g/ person per day estimated by NRCC
    (1982) and the 12.7 g/person per day estimated by NHW (1988) (section
    5.2) for the general population in Canada. The total estimated
    exposure levels in other countries may differ from this value,
    depending on product use patterns, food and water consumption, and
    levels of environmental contamination.

        Although the above estimate of exposure is based on limited
    information on residue levels and uptake rates, it is supported by the
    low levels of chlorophenols found in human tissues and fluids; in the
    few studies available, g/kg quantities have been detected in human
    tissues and fluids (section 5.2).  Occupational exposure

        The potential exposure to chlorophenols may be significant for
    certain workers employed in the lumber industry, pesticide manufacture
    and use, use of treated wood for construction, railroad ties, or
    telephone poles, and a variety of other industries in which
    chlorophenols are used as biocides. In the work place, exposure would
    be mainly through dermal absorption and inhalation; ingestion of the
    compounds is more likely to occur if eating, drinking, and smoking are
    allowed in the work area, or if proper cleansing procedures are not
    practised. The air in work areas where chlorophenols are used contains
    elevated concentrations of chlorophenols. Concentrations of 14 mg/m3
    have been reported in such work areas, but typical concentrations were
    1-3 orders of magnitude below this in work places studied recently in
    North America and Scandinavia (section 5.3). Persons working in high
    exposure areas have elevated levels of chlorophenols in their body
    fluids, particularly if their job combines dermal and inhalation
    exposure to chlorophenols. Urine levels of up to 49 mg T4CP/litre
    have been reported (section 5.3).

        Few data are available with which to model uptake and excretion of
    chlorophenols other than PCP. However, preliminary estimates of some
    occupational exposures can be derived from recent reports of
    concentrations in the urine of workers in the sawmill industry, where
    handling of treated wood and the proximity of workers to the
    open-treatment apparatus can result in relatively high uptake of

        Urinary concentrations of employees at Finnish, American, and
    Canadian sawmills have been compiled in Table 20, and have been used
    to estimate worker exposure in this industry. These estimates are
    based on two principal assumptions. First, it was assumed that urinary
    concentrations of T4CP reach a sustained level following long-term
    exposure, since Braun et al. (1979) calculated that PCP in the urine
    of exposed persons reached a fairly constant level within one week.
    Second, it was assumed that all T4CP is cleared in the urine, because
    it is known that human beings clear 86% of administered PCP in urine
    (Braun et al., 1979) and that rats clear more than 95% of single doses
    of 2,3,4,6-T4CP and 2,3,5,6-T4CP (the major tetrachlorophenols in
    commercial preparations) via the urine (Ahlborg & Larsson, 1978).

        On the basis of these assumptions, the urinary concentrations in
    Table 20, and a urine production of 1.4 litres daily, a 60-kg sawmill
    worker is estimated to take up from 2 to 42 g/kg per day on average
    (Table 20). Estimates of the exposure of workers with the highest
    urine concentrations from each study, who presumably had extensive
    dermal uptake of chlorophenates, ranged from 53 to 1142 g/kg per day.
    A more comprehensive knowledge of chlorophenol levels and fluxes and
    their dynamics would be necessary for a better estimate.

        As expected, the estimated occupational exposure is much higher
    (often 2 or more orders of magnitude) than that calculated for members
    of the general population. This difference is confirmed by levels of
    chlorophenols measured in the biological tissues and fluids of
    workers, and the ambient atmosphere (sections 5.2, 5.3), as well as
    the association of intoxications and adverse symptoms with
    occupational exposure to chlorophenols (section 9).

        Since the foregoing calculations are based on only 5 studies, all
    involving sawmills, these estimates are not directly applicable to
    other occupations and/or geographical regions.

    10.1.2  Toxic effects

        Acute lethal doses of lower chlorophenols in experimental mammals
    (section 8.1) are associated with restlessness, hyperpyrexia, rapid
    respiratory rates, at axia, and eventually dyspnoea, coma, and death.
    MCPs, DCPs, and 2,4,6-T3CP are convulsive agents, while the other
    trichlorophenols and tetrachlorophenols are not. All of the
    chlorophenols are irritating or corrosive to the skin, eyes, and
    mucuous membranes (section 8.2).

        Table 20.  Estimates of occupational exposure to tetrachlorophenols (based on urinary concentrations from recent studies
               on exposed workers)

    Situation                                                          Estimated intake                   Reference
                             Urinary concentrations (g/litre)         g/kg body weight per day)a
                             Median/mean           Maximum             Averageb       Maximum

    Finnish sawmill;         Dermal exposure primarily                Dermal exposure                     Lindroos et al. (1987)
    workers exposed to       1809.4c (median)       48 924.6          42              1142
    KY-S (NaT4CP)
    formulation; 1980-81     Respiratory exposure primarily           Respiratory exposure
                             208.8c (median)          3085.3          5                 72

    Finnish sawmill;         2841.5d,e (mean)       39 436.6d,e       66               920                Kauppinen & Lindroos (1985)
    workers exposed to                                                (1985)

    Canadian (British        423f (mean)             1479f            10                35                Currie & McDonald (1986)
    Columbia) planer                                                  (1986)
    mill; workers
    exposed to NaT4CP;

    Washington state (USA)   160.4g (mean)            2255            4                 53                Kleinman et al. (1986)
    sawmill; workers
    exposed primarily to
    NaT4CP; 1981-82

    Table 20.  (contd).

    Situation                                                          Estimated intake                   Reference
                             Urinary concentrations (g/litre)         g/kg body weight per day)a
                             Median/mean           Maximum             Averageb       Maximum

    Canadian (British        Dermal + airborne exposure               Dermal + airborne exposure          Embree et al. (1984)
    Columbia) sawmill;       1250e (mean)                             29
    workers; exposed to
    Na-T4CP; 1978-79         Airborne only                            Airborne only
                             930e                                     22

    a  For a 60-kg worker.
    b  Based on mean concentration, except for estimate from Lindroos et al. (1987), which is based on the median.
    c  Assumes all chlorophenols are T4CP, which predominates in these formulations.
    d  Not clear if sample hydrolysed.
    e  Assumes free concentrations are 10% of total concentrations.
    f  From samples collected on final morning of a 5-day work week.
    g  Grand mean for exposed workers, all dates.
    Note:  No correction for density has been made in any table entries.


        Short-term exposure of experimental animals to 2,4-DCP,
    2,4,5-T3CP, 2,4,6-T3CP, or 2,3,4,6-T4CP produces moderate adverse
    effects on the liver, kidney, and spleen, while 2,4-DCP is also
    haematotoxic and immunotoxic (section 8.2). 2-MCP, 2,4-DCP,
    2,4,5-T3CP, 2,4,6-T3CP, and 2,3,4,6-T4CP produce fetotoxic or
    embryo-toxic effects, but none of the chlorophenols tested to date has
    produced teratogenic effects. Isomers of DCP other than 2,4-DCP may
    reduce male fertility (section 8.5).

        2,4,6-T3CP and 2,3,4,6-T4CP appear to have some mutagenic
    capability; however, chlorophenols do not appear to be potent mutagens
    capable of exerting significant genotoxic effects (section 8.6). There
    is sufficient evidence that 2,4,6-T3CP (commercial grade) is an
    animal carcinogen. However, the trichlorophenol used in this study was
    not analysed for PCDD and PCDF microcontaminants. 2,4-DCP (more than
    99% pure) was found not to be carcinogenic in mice and rats. The other
    lower chlorophenols have not been adequately tested for their
    carcinogenic properties. Some chlorophenols appear to be tumour
    promoters; others do not (section 8.6).

        The microcontaminants in the commercial grades of the more highly
    chlorinated phenols can lead to toxic effects even more severe than
    those produced by the chlorophenol itself (sections 6.3, 8.9). Their
    possible significance in terms of the carcinogenicity of 2,4,6-T3CP
    should not be overlooked.

        Toxic effects in man from acute exposure to high concentrations of
    the lower chlorinated phenols include acute and chronic skin
    irritation, chloracne, respiratory disorders, recurring headaches,
    dizziness, nausea, vomiting, loss of coordination, tremor, weakness,
    and lethargy (section 9.1).

        The question of carcinogenicity in man from exposure to
    chlorophenols is a matter of controversy. IARC concluded that there is
    limited evidence of carcinogenicity from occupational exposure to
    chlorophenols. Following a review of studies published since the IARC
    evaluation, the Task Group still finds this conclusion appropriate.

    10.1.3  Risk Evaluation

        The information available to date indicates that the general
    population is exposed to low levels of chlorinated phenols. As derived
    in section 10.1, the estimated exposure to the major chlorophenols
    other than PCP of a person who does not work with these compounds is
    0.0833 g/kg per day. This burden is made up of 0.058 g 2,4-DCP/kg
    per day, 0.0013 g 2,4,5-T3CP/kg per day, and 0.024 g
    2,3,4,6-T4CP/kg per day. People who manufacture or apply
    chlorophenols predictably experience much higher levels of exposure.
    As an example, the total estimated average exposures to T4CP for
    sawmill workers ranged from 2 to 42 g/kg per day (section

        For comparison with these estimated exposures, Tolerable Daily
    Intake (TDI) levels have been calculated (from no-observed-effect
    levels determined in short- term studies) of 100 mg/kg body weight for
    2,4-DCP (mice, in feed) (Kobayashi et al., 1972), 100 mg/kg body
    weight for 2,4,5-T3CP (rats, oral) (McCollister et al., 1961), and
    10 mg/kg body weight for 2,3,4,6-T4CP (rats, oral) (Schwetz et al.,
    1974). Using an uncertainty factor of 1000 for 2,4,5- T3CP and
    2,3,4,6-T4CP, because of the lack of long-term animal data, and an
    uncertainty factor of 500 for 2,4-DCP, because of the availability of
    long-term data (WHO, 1986), the TDI values for 2,4-DCP, 2,4,5-T3CP,
    and 2,3,4,6-T4CP were estimated to be 200, 100, and 10 g/kg per day,
    respectively. The long-term carcinogenicity study available for
    2,4-DCP (section 8.7) does not provide data that would alter this
    estimate. The embryotoxicity data available for 2,4,5- T3CP (section
    8.5) were found to be of too limited significance to be taken into

        Non-occupational exposure levels are usually well below these
    values, indicating that the anticipated health hazards for the general
    population from exposure to chlorophenols other than PCP are minimal.
    The estimated occupational intakes are considerably higher, especially
    when there is skin contact with chlorophenols (Table 20). Exposure
    levels in sawmills may, in some cases, exceed the TDI values.

        If tetra- or trichlorophenol preparations are used in wood
    protection, workers can also be exposed to 2,4,6-T3CP. There is
    sufficient evidence that 2,4,6-T3CP is carcinogenic for mice and
    rats. Because of the arbitrary nature of assumptions inherent in
    developing estimates of exposure, and extrapolating from effects on
    animals to effects on human beings, risk assessments are never
    precise. Nevertheless, it is prudent to ensure that human exposure to
    2,4,6-T3CP is kept to a minimum.

        Acute exposure to high concentrations of chlorophenol formulations
    can be a significant hazard for the health of workers involved in the
    production or use of chlorophenols. While no deaths have been reported
    with exposure to chlorophenols other than PCP, fatalities due to high
    exposure to the latter are well documented. Exposures to non-PCP
    chlorophenols result in adverse signs and symptoms similar to those
    caused by PCP. Exposure to commercial formulations of chlorinated
    phenols has been associated with an increased relative risk of
    soft-tissue sarcomas, lyrephotons, and nasal and nasopharyngeal
    cancers in some studies; such associations have not been found in
    other similar studies.

        On the basis of toxicological effects and current exposure levels,
    there does not appear to be any strong reason for eliminating all use
    of chlorophenols. Furthermore, the need to reduce the levels of
    exposure to chlorophenols appears minimal as long as the necessary
    precautions to prevent high-level dermal and respiratory uptake are
    observed. Exposure of the general population is much lower, and in the
    absence of release from an industrial accident, the overall risk from
    sustained non-occupational exposure is probably negligible.
    Chlorophenols produce undesirable organoleptic effects at very low
    concentrations. Contamination of the environment and of drinking-water
    with chlorophenols above the threshold for organoleptic effects is
    therefore unacceptable. Comprehensive monitoring of chlorophenol
    levels, sources, and fluxes is essential to characterize both
    occupational and non-occupational exposure to these compounds, and to
    alert the responsible agency to potentially hazardous exposures where
    they exist.

        Microcontaminants, in particular PCDDs and PCDFs, found in
    commercial formulations of tri-, tetra-, and pentachlorophenol, are
    probably the causal agents for chloracne in human beings. PCDD and
    PCDF levels in commercial preparations should be kept as low as
    technically feasible. Care should also be taken to minimize their
    formation during the incineration of wastes containing chlorophenols.

    10.2  Evaluation of Effects on the Environment

    10.2.1  Levels of exposure

        Data on levels of chlorophenol residues other than PCP in the
    environment are limited primarily to aquatic habitats, and indicate
    that chlorophenol contamination is widespread in these systems. This
    contamination may result from either the use or the formation of
    chlorophenols, e.g., in the chlorine-bleaching process in pulp and
    paper-mills (sections 3.2, 3.3, 3.4). Where data are not available on
    levels of other chlorophenols in the environment and for evaluation
    purposes, examples of monitoring data on PCP are used. On the basis of
    relative rates of degradation and use patterns, it is likely that, in
    general, environmental levels of other chlorophenols would be lower
    than those found for PCP.

        Ambient levels of PCP in air are less than 1 ng/m3 in
    uncontaminated areas, while concentrations of several ng/m3 have been
    detected in residential areas. Other chlorophenols may well be present
    at comparable levels, but confirmatory data are lacking.

        Residues of all chlorophenol congeners have been found in fresh
    and marine waters (section 5.1.2). In Canada, concentrations are often
    undetectable at the ng/litre level in receiving waters, and only
    occasionally exceed 1 g/litre; these higher levels are only observed
    in close proximity to industrial sources of chlorophenols,

    particularly pulp and paper-mills. Ambient levels are higher in waters
    in the industrialized areas of Europe, but median concentrations still
    do not exceed 1 g/litre, and maximum concentrations in surface waters
    and groundwaters only reach several g/litre in heavily industrialized
    regions. Levels of particular chlorophenols in industrial effluents
    can reach several thousand g/litre (section 5.1.2), but dilution
    apparently reduces these to the low ambient levels observed.

        Chlorophenol concentrations in sediments are usually higher than
    those in the overlying water (section 5.1.2), as a result of
    adsorption and low rates of anaerobic degradation. Water bodies not
    receiving large chlorophenol inputs generally contain less than 1 g
    of chlorophenol congeners per kg dry sediment. Typical levels of all
    chlorophenol congeners in fresh-water sediments of industrialized
    regions are less than 50 g/kg of dry sediment. In some instances,
    hundreds or thousands of g/kg have been detected from sites adjacent
    to spills or discharges.

        Soils may contain significant quantities of chlorophenols,
    particularly at timber preservation facilities, or where phenoxy
    herbicides have been applied. Levels as high as 70 mg chlorophenols/kg
    were detected in soils from Finnish sawmills (section 5.1.3), but
    ambient levels in soil were found to be much lower (< 0.1 mg/kg).

    10.2.2  Transport

        While chlorophenols are considered to be mainly water and soil
    contaminants, some atmospheric movement also occurs. PCP has been
    detected in rain, snow, and in the air (section 5.1.1), and presumably
    other chlorophenols are also transported in this manner. Adsorption
    controls chlorophenol transport in acidic or organic soils, but is
    much less important in basic or mineral soils (section In
    surface waters, the fraction that is not degraded is incorporated into
    the sediments, most likely through adsorption on sedimenting
    particulates (section 4.1.3). While much of the chlorophenols entering
    natural waters are probably degraded by photolysis or microorganisms,
    they are moderately soluble and fairly persistent, and so can be
    transported considerable distances by water (section 4.1.3).

    10.2.3  Degradation

        Both abiotic and biotic degradation eliminate chlorophenols from
    the environment. Numerous  in vitro studies have shown that
    ultraviolet radiation can rapidly break down chlorophenols. Evidence
    suggests that photolysis is important in natural surface waters
    (section, and presumably in other exposed habitats. A large
    number of microorganisms from different habitats are able to degrade
    chlorophenols in laboratory cultures. In some instances, quantities as

    high as tens of mg/litre are eliminated in a matter of hours or days
    (section, though it is necessary to acclimate them first.
    Degradation is generally slowest for the higher chlorinated congeners
    or those with a chlorine atom in the meta position. In general,
    anaerobic biodegradation of these compounds, if it occurs at all, is
    much slower than aerobic metabolism. Some evidence suggests that
    biodegradation is faster in soil than in sediments, and slower in
    stream waters.

    10.2.4  Bioaccumulation

        Bioaccumulation of chlorophenols appears moderate, and most
    bioconcentration factors (BCFs) fall between 100 and 1000.
    Bioconcentration is usually a positive function of chlorine number.
    There are no obvious patterns in BCF in relation to the type of
    organism (for algae, plants, invertebrates, and fish). Once exposure
    is discontinued, chlorophenols clear rapidly from biota, indicating
    that the bioaccumulation observed in field studies is the result of
    long-term exposure rather than persistence.

    10.2.5  Persistence

        Chlorophenols should only persist in the environment where the
    rates of the various degradative processes are minor. Indeed, residues
    in sediments, where photolysis and apparently microbial degradation
    are minimal, have been estimated to be decades old (section 4.4).
    Herbicidal applications and spills of PCP in soils reportedly
    disappear in a matter of weeks or months.

    10.2.6  Toxic effects on environmental organisms

        Considerable overlap exists in the chlorophenol concentrations
    that are toxic for bacteria, phytoplankton, plants, invertebrates, and
    fish. Most of the LC50 and EC50 values for these organisms, which to
    date have been primarily aquatic, fall within the several mg/litre
    range (Table 16). Toxicity generally increases with the degree of
    chlorination of the phenol ring, though chlorophenols with chlorines
    in the 2 and 6 positions are often less toxic than expected on the
    basis of the number of chlorines. Particularly in the case of the
    higher chlorophenols, acute toxicity is a strong inverse function of
    pH, as the phenol form of the compound is more toxic than the ionized
    form. Exposure to chlorophenols affects a wide variety of processes in
    environmental organisms (section 7) (Table 16).

        In controlled field studies on aquatic ecosystems, exposure to
    high concentrations (100-5000 mg/litre) of lower chlorophenols
    generally impairs algal production and reproduction, alters the algal
    species composition dramatically, and reduces zooplankton biomass and
    production. The low levels of chlorophenols present in moderately
    contaminated waters have been reported to impair the flavour of fish.
    There is very little information on the toxic effects exerted by
    concentrations similar to ambient levels.

    10.2.7  Risk evaluation

        The information available to assess the environmental hazards
    presented by chlorophenols other than PCP is deficient in at least 2
    respects:  (a) knowledge of the quantities of chlorophenols entering
    the environment, and of their subsequent dynamics, is insufficient for
    all chlorophenols other than PCP; and  (b) not enough toxicology
    studies using concentrations characteristic of the environment have
    been conducted. As a result, it is not yet possible to predict
    quantitatively the environmental impact of the widespread low-level
    contamination that has recently become apparent (section 5).

        However, it is possible to get a first approximation of the hazard
    presented by a given chlorophenol, by comparing the levels that
    produce toxic effects on test organisms  in vitro with the residue
    concentrations that have been measured in the environment. The
    information for such a comparison is presented in Table 21, using data
    for aquatic organisms and environments. It is necessary to restrict
    the data in this manner because the vast majority of studies on the
    environmental toxicity of chlorophenols have been on aquatic test

        Furthermore, this focus is appropriate because many producers and
    users of chlorophenols still discharge them as wastes into water
    bodies (section 3.2.3).

        The environmental data in Table 21 include measured levels for
    each chlorophenol in water, sediment, and effluent, since these are
    the environmental sources most readily comparable with the results of
    toxicity studies. The latter data are taken from the laboratory
    toxicity studies outlined in section 5.1.2 and include the
    concentrations that cause toxic effects, the no-observed-effect
    levels, and those showing organoleptic effects in fish and
    drinking-water. In order to ensure that the comparison of
    environmental concentrations and toxic levels provides a margin of
    safety, the environmental data used for evaluation are the maximum

    values reported in highly-contaminated industrialized waters, while
    the levels producing toxic effects are the minimum levels reported to
    cause effects from a large number of studies compiled by Buikema et
    al. (1979), and Jones (1981, 1984). Table 21 is designed so that
    comparisons can be made across the rows; because of the diversity of
    test conditions, organisms, and response variables, the data on the
    toxicity of the individual compounds are not directly comparable.

        In virtually all instances, the maximum ambient levels in water
    and sediments are orders of magnitude below the lowest concentrations
    that are toxic for aquatic organisms: effects typically occur in the
    mg/litre range, while environmental levels are generally in the
    g/litre range. On this basis, it appears that the ambient
    chlorophenol levels measured in aquatic environments are unlikely to
    have adverse effects on the ecosystems receiving them, except in the
    case of accidental spills, high-concentration, point-source
    discharges, or in the immediate vicinity of manufacturers' undiluted
    waste streams. However, the elevated concentrations found in some
    industrialized regions, or in habitats adjacent to discharges, can
    compromise the flavour and/or smell of drinking-water and fish.

        It is advisable to control chlorophenol discharges into the
    environment at levels that would not increase the present
    environmental concentrations, in view of the taste and odour effects
    of chlorophenols and the lack of data on the long-term effects on
    ecosystems from the present low levels of chlorophenols detected.
    Furthermore, the levels of such microcontaminants as PCDDs and PCDFs
    in technical formulations of T3CP and T4CP should be reduced as much
    as possible, in order to decrease the levels of such toxic chemicals
    released into the environment.

        Table 21.  Maximum reported water, sediment, and effluent levels, contrasted with minimum levels producing toxic and organoleptic
               effects and no-observed-effect levels

    Compound       Maximum reported                    Lowest reported levels         No-observed-effect      Organoleptic
                   environmental levels                causing toxic effects          level (NOEL)            threshold in water

                   Water    Sedimentn    Effluents     Level        Effect            Level    Parameter      Drinking-    Fish
                   (g/     (g/kg)      (g/litre)    (g/litre)   (g/litre)                                 watera      flesha

    2-MCP          2.3m                  4p            2600         Daphnia           1000     Daphnia                         60
                                                                    magna                      magna
                                                                    48-h LC50b                 survivalb

    3-MCP          6.0m     43           6p            1800         Unidentified      10000    Chlorella      0.1              25
                                                                    fish                       pyrenoidosa
                                                                    24-h TLmd                  growthc

    4-MCP          3.9m                  150q          4100         Daphnia           500      Estuarine      0.1              45
                                                                    magnab                     phytoplankton
                                                                    48-h LC50                  growthe

    2,3-DCP        0.72m    2.2                                                                               0.04             84

    Table 21. (contd).

    Compound       Maximum reported                    Lowest reported levels         No-observed-effect      Organoleptic
                   environmental levels                causing toxic effects          level (NOEL)            threshold in water

                   Water    Sedimentn    Effluents     Level        Effect            Level    Parameter      Drinking-    Fish
                   (g/     (g/kg)      (g/litre)    (g/litre)   (g/litre)                                 watera      flesha

    2,4-DCP        0.59m    10           3304          100          Crayfish                                  0.3-8.0          1.0
                                                                    elevation of

    2,5-DCP        0.29m    11                                                                                0.5              23

    2,6-DCP        0.45m    31           2204          4000         Salmo trutta                              0.2-2.0          35
                                                                    24-h LC50g

    3,4-DCP        0.23m    49                         5000         Fishhdeath                                0.3

    3,5-DCP        0.52m    12                         1500         Shrimp
                                                                    96-h lethal

    2,3,4-T3CP     0.04n    0.8          3.64          2000         Shrimp
                                                                    96-h lethal

    2,3,5-T3CP     0.28n    11                         800          Salmo truttag
                                                                    24-h LC50

    Table 21. (contd).

    Compound       Maximum reported                    Lowest reported levels         No-observed-effect      Organoleptic
                   environmental levels                causing toxic effects          level (NOEL)            threshold in water

                   Water    Sedimentn    Effluents     Level        Effect            Level    Parameter      Drinking-      Fish
                   (g/     (g/kg)      (g/litre)    (g/litre)   (g/litre)                                 watera        flesha

    2,3,6-T3CP     0.36n                               2700         Shrimp                                    0.5
                                                                    96-h lethal

    2,4,5-T3CP     0.66m    15           2400q         640          Palaemonetes      100      Rainbow trout  1.0              52
                                                                    96-h LC50j

    2,4,6-T3CP     2.5m     3.7          3120q         .0.5         Guppy             < 410    Daphnia        2.0
                                                                    fecundity                  magna
                                                                    offspring                  survival

    2,4,6-T3CP     2.5m     3.7          3120q         > 100-       Fathead minnow
                                                         < 1000     96-h TLm

    Table 21. (contd).

    Compound       Maximum reported                    Lowest reported levels         No-observed-effect      Organoleptic
                   environmental levels                causing toxic effects          level (NOEL)            threshold in water

                   Water    Sedimentn    Effluents     Level        Effect            Level    Parameter      Drinking-    Fish
                   (g/     (g/kg)      (g/litre)    (g/litre)   (g/litre)                                 watera      flesha

    2,3,4,5-T4CP   0.02n    8.9          12q           < 300        Grass shrimp

    2,3,4,6-T4CP   3r       4.9          2100q         290          Daphnia           10       Daphnia        1.0
                                                                    magna                      magnab
                                                                    48-h LC50b                 survival

    2,3,5,6-T4CP   5r       2.8          35            570          Daphnia 10                 Daphnia
                                                                    magna                      magna
                                                                    48-h LC50b                 survivalb


    a  Organoleptic threshold is for drinking-water (US EPA, 1980c) and ambient water that leads to the tainting of fish
       flesh (Shumway & Palensky, 1973).
    b  LeBlanc (1980).                         j  Rao et al. (1981).
    c  Huang & Gloyna (1968).                  k  Virtanen & Hattula (1982).
    d  Ingols et al. (1966).                   l  Barnhart & Campbell (1972).
    e  Erickson & Hawkins (1980).              m  Wegman & Hofstee (1979).
    f  Telford (1974).                         n  Wegman & van den Broek (1983).
    g  Hattula et al. (1981b).                 p  Jolley et al. (1975).
    h  Jones (1981).                           q  Garrett (1980).
    i  McLeese et al. (1979).                  r  Zoeteman et al. (1981).


    11.1  Production

     (a) The concentrations of microcontaminants in chlorophenols and
    products derived from them should be determined and specified.

     (b) Levels of PCDDs and PCDFs in chlorophenols and related products
    should be kept as low as is technically possible.

     (c) Since data on the quantities of chlorophenols produced and
    consumed are not available for most countries, international agencies
    should seek the assistance of industry to compile such data in
    different countries.

    11.2  Disposal

    (a) Disposal of chlorophenols and chlorophenol-contaminated waste
    should be carried out in a manner that minimizes their release into
    the environment. Contaminated waste waters should undergo primary and
    secondary treatment. Chlorophenols should only be incinerated at high
    temperatures and under strictly controlled conditions.

     (b) Contamination of surface and ground waters with chlorophenols
    arising as a result of industrial chlorination processes or waste
    treatments using chlorine should be avoided as far as is technically

    11.3  Occupational Exposure

     (a) Work-place exposure to chlorophenols should be minimized, and
    absorption of these compounds through the dermal and inhalation routes
    prevented, by:

    --  enclosure and automation of industrial processes that use

    --  adequate ventilation of the work area;

    --  provision of appropriate protective clothing for employees working
        with chlorophenols;

    --  provision of proper washing and laundry facilities;

    --  instruction of workers in the safe use and handling of
        chlorophenols, the importance of personal hygiene (washing before
        eating or smoking, showering before leaving work, and daily
        laundering of clothing), and the application of proper emergency

    --  provision of eating and rest areas in the work place that are
        isolated from potential chlorophenol contamination.

     (b) The effectiveness of measures to reduce occupational exposure
    should be surveyed by monitoring both the work-place air and the urine
    of the workers.

    11.4  General Population Exposure

     (a) The availability and use of consumer products containing
    chlorophenols should be reduced wherever practicable.

     (b) Products containing chlorophenols should be clearly labelled by
    the manufacturer to alert the consumer to their toxicity and to
    instruct consumers in the safe use and handling of these products.

     (c) The use of tri- and tetrachlorophenols for wood preservation
    should be avoided where such wood is to be used:

    --  for shipping or storing food;

    --  for the retention of soil on which food may be grown;

    --  for animal housing or bedding on farms.

    11.5  Recommendations for Future Research

    11.5.1  Environmental Aspects

        Given the continued release of chlorophenols into the environment,
    research is needed to study:

     (a) the transport and distribution of chlorophenols in the

     (b) the effects of long-term exposure to chlorophenols on both
    aquatic and terrestrial organisms at concentrations typical of the

     (c) the suitability of controlled landfill sites for the disposal of
    chlorophenols and related wastes;

     (d) means of reducing the contribution of industrial and municipal
    chlorination to the overall environmental releases of chlorophenols.

    11.5.2  Toxicology

        The toxicology database for chlorophenols other than PCP has major
    deficiencies, particularly for tetrachlorophenols. A more accurate
    estimate of the risk posed by these chemicals necessitates research

     (a) uptake, distribution, metabolism, and excretion of
    chlorophenols, especially in man;

     (b) further study of the effects of chlorophenols on reproduction;

     (c) the  in vivo genotoxic potential of chlorophenols;

     (d) long-term carcinogenicity studies with pure and technical grade
    2,4,5-T3CP, 2,4,6-T3CP, and 2,3,4,6-T4CP;

     (e) the cancer-promoting potential of chlorophenols;

     (f) the mechanism of toxicity of chlorophenols at the molecular

     (g) the extent to which the toxic effects exerted by technical grade
    chlorophenols are attributable to microcontaminants;

     (h) the contribution made by the biotransformation of other
    chlorinated compounds (e.g., hexachlorobenzene) to the human body
    burden of chlorophenols.

    11.5.3  Epidemiology

     (a) Epidemiological investigations of previously-studied cohorts
    should be followed-up and updated.

     (b) Studies on new groups of workers exposed specifically to
    chlorophenols, i.e., sawmill employees working with these compounds,
    should be conducted. End-points studied should not only be cancers,
    but should also include pulmonary, reproductive, and other effects.

     (c) The higher chlorinated PCDDs and PCDFs, which occur as
    contaminants in several chlorophenols, have long half-lives in human
    beings and can therefore be used as indicators of exposure to the
    higher chlorophenols. Since the present contradictory results from
    epidemiological studies may, in part, be because of inaccurate
    information on exposure to CPs, the potential use of PCDD and PCDF
    concentrations in human tissues and fluids as markers of previous
    exposure to these chlorophenols should be investigated.


        A guideline value of 10 g/litre was recommended by WHO (WHO,
    1984) for 2,4,6-trichlorophenol in drinking-water, based on animal
    carcinogenicity data using a conservative mathematical model. In the
    supporting documentation for this guideline value (WHO, 1985), it was
    noted that the taste threshold level for 2,4,6-T3CP was 1.0 g/litre
    and that, on the basis of aesthetic qualities, the level would be
    0.1 g/litre. Guideline values for other individual CPs were not set,
    but the odour threshold concentration of 0.1 g/litre was considered
    appropriate for chlorophenols other than pentachlorophenol.

        The carcinogenicity of 2,4,5- and 2,4,6-T3CP has been evaluated
    by the International Agency for Research on Cancer (IARC, 1979, 1986).
    It was concluded that: there was sufficient evidence for
    carcinogenicity in animals for 2,4,6-T3CP and inadequate data for the
    assessment of the carcinogenicity of 2,4,5-T3CP in animals. IARC
    (1986) also concluded that there was limited evidence for the
    carcinogenicity of occupational exposures to all chlorophenols for
    human beings. Although not stated directly in the IARC monographs,
    occupational exposures were primarily to T3CP and T4CP formulations.

        Regulatory standards for chlorophenols established by national
    bodies in different countries and the EEC are summarized in the Legal
    File of the International Register of Potentially Toxic Chemicals
    (IRPTC, 1986).


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    See Also:
       Toxicological Abbreviations