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    UNITED NATIONS ENVIRONMENT PROGRAMME
    INTERNATIONAL LABOUR ORGANISATION
    WORLD HEALTH ORGANIZATION


    INTERNATIONAL PROGRAMME ON CHEMICAL SAFETY



    ENVIRONMENTAL HEALTH CRITERIA 181





    CHLORINATED PARAFFINS






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

    First draft prepared by Dr K. Kenne and Professor U.G. Ahlborg,
    Institute of Environmental Medicine, Karolinska Institute, Stockholm,
    Sweden


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


    World Health Organization
    Geneva, 1996

         The International Programme on Chemical Safety (IPCS) is a joint
    venture of the United Nations Environment Programme (UNEP), the
    International Labour Organisation (ILO), and the World Health
    Organization (WHO). The main objective of the IPCS is to carry out and
    disseminate evaluations of the effects of chemicals on human health
    and the quality of the environment. Supporting activities include
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    risk-assessment methods that could produce internationally comparable
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    Other activities carried out by the IPCS include the development of
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    Agriculture Organization of the United Nations, WHO, the United
    Nations Industrial Development Organization and the Organisation for
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    following recommendations made by the 1992 UN Conference on
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    is to promote coordination of the policies and activities pursued by
    the Participating Organizations, jointly or separately, to achieve the
    sound management of chemicals in relation to human health and the
    environment.

    WHO Library Cataloguing in Publication Data

    Chlorinated paraffins.

    (Environmental health criteria ; 181)

    1.Paraffin - adverse effects   2.Paraffin - toxicity
    3.Environmental exposure   I.Series

    ISBN 92 4 157181 0                 (NLM Classification: QV 800)
    ISSN 0250-863X

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    (c) World Health Organization 1996

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    CONTENTS

    ENVIRONMENTAL HEALTH CRITERIA FOR CHLORINATED PARAFFINS

    Preamble

    1. SUMMARY

        1.1. Properties, uses and analytical methods
        1.2. Sources of human and environmental exposure
        1.3. Environmental distribution and transformation
        1.4. Environmental levels and human exposure
        1.5. Kinetics and metabolism
        1.6. Effects on laboratory mammals and  in vitro
              test systems
        1.7. Effects on humans
        1.8. Effects on other organisms in the laboratory
              and field
        1.9. Evaluation of human health risks and effects on the
              environment

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

        2.1. Identity
              2.1.1. Relative molecular mass
              2.1.2. Common names
                      2.1.2.1   CAS registry number and names
                      2.1.2.2   Synonyms
              2.1.3. Technical products
        2.2. Chemical and physical properties
        2.3. Analysis
              2.3.1. Sampling
              2.3.2. Analytical methods

    3. SOURCES OF HUMAN AND ENVIRONMENTAL EXPOSURE

        3.1. Natural occurrence
        3.2. Anthropogenic sources
              3.2.1. Production levels and processes
              3.2.2. Uses
              3.2.3. Loss into the environment

    4. ENVIRONMENTAL TRANSPORT, DISTRIBUTION AND TRANSFORMATION

        4.1. Transport and distribution between media
        4.2. Transformation
              4.2.1. Abiotic transformation

              4.2.2. Biodegradation
                      4.2.2.1   Short chain length chlorinated
                                paraffins
                      4.2.2.2   Long chain length chlorinated
                                paraffins
                      4.2.2.3   Comparative studies
        4.3. Bioaccumulation and biomagnification
              4.3.1. Summary
              4.3.2. Aquatic vertebrates
                      4.3.2.1   Short chain length chlorinated
                                paraffins
                      4.3.2.2   Intermediate chain length chlorinated
                                paraffins
                      4.3.2.3   Long chain length chlorinated
                                paraffins
              4.3.3. Aquatic invertebrates
                      4.3.3.1   Short chain length chlorinated
                                paraffins
                      4.3.3.2   Intermediate chain length chlorinated
                                paraffins
                      4.3.3.3   Long chain length chlorinated
                                paraffins
                      4.3.3.4   Comparative studies
              4.3.4. Aquatic plants

    5. ENVIRONMENTAL LEVELS AND HUMAN EXPOSURE

        5.1. Environmental levels
              5.1.1. Air
              5.1.2. Water and sediment
              5.1.3. Soil
              5.1.4. Aquatic and terrestrial organisms
              5.1.5. Food and beverages
        5.2. General population exposure
              5.2.1. Concentrations in human tissues
        5.3. Occupational exposure

    6. KINETICS AND METABOLISM IN LABORATORY ANIMALS

        6.1. Absorption
              6.1.1. Oral exposure
              6.1.2. Dermal exposure
              6.1.3. Inhalation exposure
        6.2. Distribution
              6.2.1. Short chain length chlorinated paraffins
                      6.2.1.1   Mouse
                      6.2.1.2   Rat

              6.2.2. Intermediate chain length chlorinated paraffins
                      6.2.2.1   Rat
                      6.2.2.2   Mouse
                      6.2.2.3   Bird
                      6.2.2.4   Fish
              6.2.3. Long chain length chlorinated paraffins
                      6.2.3.1   Rat
                      6.2.3.2   Fish
                      6.2.3.3   Mussel
              6.2.4. Comparative studies
        6.3. Metabolic transformation
              6.3.1. Short chain length chlorinated paraffins
              6.3.2. Intermediate chain length chlorinated paraffins
        6.4. Elimination and excretion
              6.4.1. Short chain length chlorinated paraffins
              6.4.2. Intermediate chain length chlorinated paraffins
                      6.4.2.1   Rat
                      6.4.2.2   Mouse
                      6.4.2.3   Bird
              6.4.3. Long chain length chlorinated paraffins
              6.4.4. Comparative studies

    7. EFFECTS ON LABORATORY MAMMALS AND  IN VITRO TEST SYSTEMS

        7.1. Acute exposure
              7.1.1. Lethal doses
              7.1.2. Non-lethal doses
                      7.1.2.1   Oral route
                      7.1.2.2   Inhalation route
                      7.1.2.3   Intraperitoneal route
              7.1.3. Skin and eye irritation
                      7.1.3.1   Short chain length chlorinated
                                paraffins
                      7.1.3.2   Intermediate and long chain length
                                chlorinated paraffins
              7.1.4. Skin sensitization
        7.2. Repeated exposure
              7.2.1. Oral route
                      7.2.1.1   Short chain length chlorinated
                                paraffins
                      7.2.1.2   Intermediate chain length chlorinated
                                paraffins
                      7.2.1.3   Long chain length chlorinated
                                paraffins
                      7.2.1.4   Comparative studies
              7.2.2. Intraperitoneal route
                      7.2.2.1   Short chain length chlorinated
                                paraffins
                      7.2.2.2   Intermediate chain length chlorinated
                                paraffins
                      7.2.2.3   Comparative studies

        7.3. Neurotoxicity
              7.3.1. Short chain length chlorinated paraffins
              7.3.2. Intermediate chain length chlorinated paraffins
        7.4. Reproductive toxicity, embryotoxicity and
              teratogenicity
              7.4.1. Reproduction
              7.4.2. Embryotoxicity and teratogenicity
                      7.4.2.1   Short chain length chlorinated
                                paraffins
                      7.4.2.2   Intermediate chain length chlorinated
                                paraffins
                      7.4.2.3   Long chain length chlorinated
                                paraffins
        7.5. Mutagenicity and related end-points
              7.5.1. Prokaryotes
              7.5.2. Mammalian cells
                      7.5.2.1    In vitro studies
                      7.5.2.2    In vivo studies
                      7.5.2.3   Cell transformation
        7.6. Long-term exposure and carcinogenicity
              7.6.1. Oral route
                      7.6.1.1   Short chain length chlorinated
                                paraffins
                      7.6.1.2   Long chain length chlorinated
                                paraffins

    8. EFFECTS ON HUMANS

        8.1. General population exposure
              8.1.1. Controlled human studies
        8.2. Occupational exposure

    9. EFFECTS ON OTHER ORGANISMS IN THE LABORATORY AND FIELD

        9.1. Laboratory experiments
              9.1.1. Microorganisms
              9.1.2. Aquatic organisms
                      9.1.2.1   Aquatic plants
                      9.1.2.2   Invertebrates
                      9.1.2.3   Fish
              9.1.3. Terrestrial organisms
        9.2. Field observations

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

        10.1. Evaluation of human health risks
              10.1.1. Exposure levels
              10.1.2. Toxic effects
              10.1.3. Risk evaluation
                      10.1.3.1  Short chain compounds
                      10.1.3.2  Intermediate chain compounds
                      10.1.3.3  Long chain compounds

        10.2. Evaluation of effects on the environment
              10.2.1. Exposure levels
              10.2.2. Toxic effects
              10.2.3. Risk evaluation

    11. RECOMMENDATIONS FOR PROTECTION OF THE ENVIRONMENT

    12. FUTURE RESEARCH

    13. PREVIOUS EVALUATION BY INTERNATIONAL ORGANIZATIONS

    REFERENCES

    RESUME

    RESUMEN
    

    NOTE TO READERS OF THE CRITERIA MONOGRAPHS

        Every effort has been made to present information in the criteria
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    Environmental Health Criteria

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    WHO TASK GROUP ON ENVIRONMENTAL HEALTH CRITERIA FOR CHLORINATED
    PARAFFINS

     Members

    Professor U.G. Ahlborg, Institute of Environmental Medicine,
       Karolinska Institute, Stockholm, Sweden  (Vice-Chairman)

    Dr D. Anderson, British Industry Biological Research Association
       (BIBRA) Toxicology International, Carshalton, Surrey, United
       Kingdom

    Dr T. Beulshausen, Federal Environment Agency, Berlin, Germany

    Dr R.S. Chhabra, Environmental Toxicology Program, National Institute
       of Environmental Health Sciences, Research Triangle Park, North
       Carolina, USA

    Dr N. Gregg, Health and Safety Executive, Bootle, Merseyside, United
       Kingdom

    Mr P.D. Howe, Institute of Terrestrial Ecology, Monks Wood,
       Huntingdon, Cambridgeshire, United Kingdom  (Joint Rapporteur)

    Dr B. Jansson, Institute of Applied Environmental Research, Stockholm
       University, Solna, Sweden

    Dr K. Kenne, Institute of Environmental Medicine, Karolinska
       Institute, Stockholm, Sweden  (Joint Rapporteur)

    Dr M.E. Meek, Environmental Health Directorate, Health Canada, Ottawa,
       Ontario, Canada  (Chairman)

     Representatives of other Organizations

    Dr P. Montuschi, Institute of Pharmacology, Faculty of Medicine and
       Surgery, Catholic University of the Sacred Heart, Rome, Italy
       (Representing the International Union of Pharmacology)

    Mr D. Farrar, Occupational Health, ICI Chemicals and Polymers Limited,
       Runcorn, Cheshire, United Kingdom
       (Representing the European Centre for Ecotoxicology and Toxicology
       of Chemicals)

     Secretariat

    Dr E.M. Smith, International Programme on Chemical Safety, World
       Health Organization, Geneva, Switzerland  (Secretary)

    Mr J.D. Wilbourn, Unit of Carcinogen Identification and Evaluation,
       International Agency for Research on Cancer, Lyon, France

    ENVIRONMENTAL HEALTH CRITERIA FOR CHLORINATED PARAFFINS

         A WHO Task Group on Environmental Health Criteria for Chlorinated
    Paraffins met at the World Health Organization, Geneva, from 20 to 24
    March 1995.  Dr E.M. Smith, IPCS, welcomed the participants on behalf
    of Dr M. Mercier, Director of the IPCS, and on behalf the three IPCS
    cooperating organizations (UNEP/ILO/WHO).  The Group reviewed and
    revised the draft and made an evaluation of the risks for human health
    and the environment from exposure to chlorinated paraffins.

         The first draft was prepared at the Institute of Environmental
    Medicine, Karolinska Institute, Stockholm, Sweden, by Dr K. Kenne and
    Professor U.G. Ahlborg.  The second draft, incorporating comments
    received following circulation of the first drafts to the IPCS contact
    points for Environmental Health Criteria monographs, was also prepared
    by Dr Kenne and Professor Ahlborg.

         Dr E.M. Smith and Dr P. Jenkins, both of the IPCS Central Unit,
    were responsible for the scientific aspects of the monograph and for
    the technical editing, respectively.

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

    ABBREVIATIONS

    APDM     aminopyrine demethylase
    BCF      bioconcentration factor
    CD       coulometric detection
    CP       chlorinated paraffins
    CP-LH    chlorinated paraffin with long chain length and high degree
             of chlorination
    CP-LL    chlorinated paraffin with long chain length and low degree of
             chlorination
    CP-MH    chlorinated paraffin with medium chain length and high degree
             of chlorination
    CP-ML    chlorinated paraffin with medium chain length and low degree
             of chlorination
    CP-SH    chlorinated paraffin with short chain length and high degree
             of chlorination
    CP-SL    chlorinated paraffin with short chain length and low degree
             of chlorination
    EC50       median effective concentration
    ECD      electron capture detection
    GC       gas chromatography
    LC50     median lethal concentration
    LOAEL    lowest-observed-adverse-effect level
    LOEC     lowest-observed-effect concentration
    LOEL     lowest-observed-effect level
    LT50     median lethal time
    MS       mass spectrometry
    NCI      negative ion chemical ionization
    NOAEL    no-observed-adverse-effect level
    NOEL     no-observed-effect level
    PCB      polychlorinated biphenyl
    PVC      polyvinyl chloride
    TDI      tolerable daily intake
    TLC      thin-layer chromatography
    TSH      thyroid stimulating hormone
    UDP      uridine diphosphate

    1.  SUMMARY

    1.1  Properties, uses and analytical methods

         Chlorinated paraffins (CPs) are produced by chlorination of
    straight-chained paraffin fractions.  The carbon chain length of
    commercial chlorinated paraffins is usually between 10 and 30 carbon
    atoms, and the chlorine content is usually between 40 and 70% by
    weight.  Chlorinated paraffins are viscous colourless or yellowish
    dense oils with low vapour pressures, except for those of long carbon
    chain length with high chlorine content (70%), which are solid. 
    Chlorinated paraffins are practically insoluble in water, lower
    alcohols, glycerol and glycols, but are soluble in chlorinated
    solvents, aromatic hydrocarbons, ketones, esters, ethers, mineral oils
    and some cutting oils.  They are moderately soluble in unchlorinated
    aliphatic hydrocarbons.

         Chlorinated paraffins consist of extremely complex mixtures,
    owing to the many possible positions for the chlorine atoms. The
    products can be subdivided into six groups depending on chain length
    (short C10-13, intermediate C14-17 and long C18-30) and degree of
    chlorination (low (< 50%) and high (> 50%)).

         Chlorinated paraffins are used worldwide in widespread
    applications such as plasticizers in plastics (e.g., PVC), extreme
    pressure additives in metal working fluids, flame retardants and
    additives in paints.  Technical grade chlorinated paraffins may be
    contaminated by isoparaffins, aromatic compounds and metals, and
    normally contain stabilizers, which are added to inhibit
    decomposition.

         The analysis of chlorinated paraffins is difficult due to the
    extreme complexity of these mixtures.  In environmental samples, this
    is further complicated by interference from other compounds.  Analyses
    often require extensive clean-up of the samples and the use of
    specific detection methods.  Early methods were based on thin-layer
    chromatography for the clean-up and an unspecific argentation
    detection method on the plates.  Methods based on different column
    liquid chromatography are currently used for the clean-up, although it
    is difficult to isolate the chlorinated paraffins due to their wide
    range of physical properties.  Specific detection methods are
    therefore used; gas chromatography combined with mass spectrometry is
    now the most common technique.  The use of negative ions makes the
    detection even more specific.  Although use of these sophisticated
    techniques has improved the ability to analyse chlorinated paraffins,
    it is still impossible to determine exact concentrations.  Reported
    results should be regarded only as estimates of the true values.

    1.2  Sources of human and environmental exposure

         Chlorinated paraffins are not known to occur naturally.

         Chlorinated paraffins are produced by reacting liquid paraffin
    fractions with pure chlorine gas.  The reaction may require the use of
    a solvent, and often ultraviolet light is used as a catalyst.  In
    1985, the estimated world production of chlorinated paraffins was
    300 000 tonnes.

         The widespread uses of chlorinated paraffins probably provide the
    major source of environmental contamination.  Chlorinated paraffins
    may be released into the environment from improperly disposed
    metal-working fluids containing chlorinated paraffins or from polymers
    containing chlorinated paraffins.  Loss of chlorinated paraffins by
    leaching from paints and coatings may also contribute to environmental
    contamination.  The potential for loss during production and transport
    is expected to be less than that during product use and disposal.

         Owing to their thermal instability, chlorinated paraffins are
    expected to be degraded by incineration and thus would not be expected
    to volatilize in exhaust gases from incinerators.  However, it has
    been demonstrated that chlorinated aromatic compounds such as
    polychlorinated biphenyls, naphthalenes and benzenes are formed by
    pyrolysis of chlorinated paraffins under certain conditions.

    1.3  Environmental distribution and transformation

         Chlorinated paraffins adsorb strongly to sediment.  In water they
    are probably transported adsorbed on suspended particles, and in the
    atmosphere adsorbed to airborne particulates (and possibly in the
    vapour phase).  The half-lives for chlorinated paraffins in air have
    been estimated to range from 0.85 to 7.2 days, a period sufficiently
    long that the possibility of long-range transport cannot be excluded.

         Chlorinated paraffins are not readily biodegradable.  Short
    carbon chain length chlorinated paraffins with a chlorine content of
    less than 50% appear to be degradable under aerobic conditions with
    acclimated microorganisms, whereas the degradation appears inhibited
    at a chlorine content above 58%. Intermediate and long chain length
    chlorinated paraffins are degraded more slowly.

         Chlorinated paraffins are bioaccumulated in aquatic organisms,
    and the reported bioconcentration factors (BCFs) are in the range of 7
    to 7155 for fish and 223 to 138 000 for mussels.  In fish, chlorinated
    paraffins of short chain length are accumulated to a higher degree
    than intermediate and long chain length chlorinated paraffins.
    Radioactivity has been found mainly in bile, intestine, liver, fat and
    gills after administration of radiolabelled chlorinated paraffins. The
    uptake of chlorinated paraffins seems to be more efficient for short

    chlorinated paraffins with low chlorine content; the elimination rate
    is slowest for short chlorinated paraffins with high chlorine content. 
    The retention in fat-rich tissues appears to increase with increasing
    degree of chlorination.

    1.4  Environmental levels and human exposure

         Few data on levels of chlorinated paraffins in the environment
    are available.  Chlorinated paraffins have been detected in marine
    water samples in the United Kingdom at levels below 4 µg/litre.  In
    non-marine waters, levels below 6 µg/litre in the United Kingdom have
    been reported; in Germany, concentrations determined in 1994 were in
    the range of 0.08-0.28 µg/litre.  In water in the USA, concentrations
    were generally less than 0.03 µg/litre, although levels were above 1.0
    µg/litre in a small proportion (1.2%) of samples. In marine sediments,
    levels up to 600 µg/kg wet weight have been reported, and in
    non-marine sediments in the United Kingdom concentrations were up to
    15 000 µg/kg in industrialized regions and 1000 µg/kg in areas
    remote from industry. In sediments in an impoundment lagoon from a
    chlorinated paraffin manufacturing plant in the USA, concentrations as
    high as 170 000 µg/kg dry weight of long chain length chlorinated
    paraffins, 50 000 µg/kg of intermediate chain length chlorinated
    paraffins and 40 000 µg/kg of short chain length chlorinated paraffins
    were reported. In Germany, levels up to 83 µg/kg dry weight of C10-13
    and up to 370 µg/kg dry weight of C14-17 were reported in sediments in
    1994.  In Japan, levels in sediment ranged up to 8500 µg/kg.

         Chlorinated paraffins have been detected in various organisms. 
    Chlorinated paraffins are present in terrestrial mammals in Sweden at
    concentrations in the range of 32-88 µg/kg tissue (140-4400 µg/kg
    lipid).  However, chlorinated paraffins were not detected in sheep
    which were grazed remote from production of chlorinated paraffins in
    the United Kingdom.  In birds in the United Kingdom, concentrations
    ranged up to 1500 µg/kg and in fish in Sweden and the United Kingdom,
    levels ranged up to 200 µg/kg.  In mussels collected in the USA and
    United Kingdom, concentrations up to 400 µg/kg were reported. 
    However, levels of C10-20 in mussels collected close to a chlorinated
    paraffin plant effluent discharge ranged up to 12 000 µg/kg. 
    Chlorinated paraffins have also been detected in post mortem human
    tissues, i.e. in adipose tissue (median level of 100-190 µg/kg),
    kidney (median level below 90 µg/kg) and liver (median level below 90
    µg/kg).  In one limited survey, chlorinated paraffins, mostly C10-20,
    were present at levels of up to 500 µg/kg in approximately 70% of the
    samples of various food products.

         Information on occupational exposure to chlorinated paraffins is
    limited.  Very low levels of exposure to aerosols of short chain
    chlorinated paraffins (0.003-1.2 mg/m3) have been found to be
    associated with their use as metal-working fluids, although there is
    no information available on the proportion that is inhalable.  On the
    basis of mathematical modelling of exposure without any control
    measures, high levels of dermal contact (5-15 mg/cm2 per day) were

    estimated for speciality metal-working fluids which contain very high
    levels of short chain chlorinated paraffins, although absorption would
    be expected to be low.  Control measures would reduce dermal exposure.

    1.5  Kinetics and metabolism

         The toxicokinetics of chlorinated paraffins have been studied
    in experimental animals.  Adequate information for humans is not
    available.  Possible differences in toxicokinetics as a result of
    different chain lengths have not been sufficiently investigated. 
    Although the extent of absorption of chlorinated paraffins after oral
    administration is unknown, it appears to decrease with increasing
    chain length and degree of chlorination.  Percutaneous absorption may
    also occur depending on chain length, but would be limited (less than
    1% of a topical C18 dose).  No data on absorption via the lung is
    available.

         Distribution of chlorinated paraffins occurs mainly in the liver,
    kidney, intestine, bone marrow, adipose tissue and ovary.  Information
    on retention is insufficient but a low degree of chlorination may
    enhance retention time due to slower redistribution.  Chlorinated
    paraffins or their metabolites are present in the central nervous
    system up to 30 days after administration.  They may cross the
    blood-placental barrier.  There is no adequate information on the
    pathways of metabolism of chlorinated paraffins, although in
    radiolabelling studies CO2 has been identified as an end-product.

         Chlorinated paraffins may be excreted via the renal, biliary and
    the pulmonary routes (as CO2).  The relative extent of excretion
    via the different routes is difficult to establish due to the
    wide variability in different studies.  The total elimination of
    chlorinated paraffins decreases as the chlorine content increases, and
    compounds with high degrees of chlorination are mainly excreted (more
    than 50%) as CO2.  Chlorinated paraffins may be excreted in milk.

    1.6  Effects on laboratory mammals and  in vitro test systems

         The acute oral toxicity of chlorinated paraffins of various chain
    lengths is low. Toxic effects such as muscular incoordination and
    piloerection were most evident following single exposure to short
    chain length chlorinated paraffins.  On the basis of very limited
    data, the acute toxicity by the inhalation and dermal routes also
    appears to be low.  Mild skin and eye irritation has been observed
    after application of short and intermediate (skin irritation)
    chain length chlorinated paraffins.  Results of several studies
    indicate that short chain chlorinated paraffins do not induce skin
    sensitization.

         In repeated dose toxicity studies by the oral route, the liver,
    kidney and thyroid are the primary target organs for the toxicity of
    the chlorinated paraffins.  For the short chain compounds, increases

    in liver weight have been observed at lowest doses (lowest-observed-
    effect level is 50 to 100 mg/kg body weight per day and no-observed-
    effect level is 10 mg/kg body weight per day in rats).  At higher
    doses, increases in the activity of hepatic enzymes, proliferation
    of smooth endoplasmic reticulum and peroxisomes, replicative DNA
    synthesis, hypertrophy, hyperplasia and necrosis of the liver have
    also been observed.  Decreases in body weight gain (125 mg/kg body
    weight per day in mice), increases in kidney weight (100 mg/kg body
    weight per day in rats), replicative DNA synthesis in renal cells
    (313 mg/kg body weight per day) and nephrosis (625 mg/kg body weight
    per day in rats) have also been observed.  Increases in thyroid
    weight, and hypertrophy and hyperplasia of the thyroid (LOEL of
    100 mg/kg body weight per day in rats) and replicative DNA synthesis
    in thyroid follicular cells (LOEL of 313 mg/kg body weight per day)
    have been reported.  At higher doses (1000 mg/kg body weight per day),
    thyroid function is affected, as determined by free and total levels
    of plasma thyroxine and increased plasma thyroid-stimulating hormone
    in rats.

         For the intermediate chain compounds, effects observed at lowest
    doses are generally increases in liver and kidney weight (LOEL in rats
    of 100 mg/kg body weight per day; NOAEL in rats of 10 mg/kg body
    weight per day).  Increases in serum cholesterol and "mild, adaptive"
    histological changes in the thyroid have been reported at similar
    doses in female rats (NOAEL of 4 mg/kg body weight per day).

         For the long chain compounds, effects observed at lowest doses
    are multifocal granulomatous hepatitis and increased liver weights in
    female rats (LOAEL of 100 mg/kg body weight per day).

         In the only identified reproduction study, no adverse
    reproductive effects were reported following exposure of rats to an
    intermediate chain length chlorinated paraffin with 52% chlorine. 
    However, survival and body weights of the exposed pups were reduced
    (LOEL for non-significant decrease in body weight of 5.7-7.2 mg/kg
    body weight per day; LOAEL for decreased survival of 60-70 mg/kg body
    weight per day). In a limited number of studies of the developmental
    effects of the short, medium and long chain chlorinated paraffins,
    adverse effects in the offspring were observed for the short chain
    compounds only, at maternally toxic doses in rats (2000 mg/kg body
    weight per day).  For the medium and long chain compounds, no effects
    on the offspring were observed even at very high doses (1000 to
    5000 mg/kg body weight per day).

         Chlorinated paraffins do not appear to induce mutations in
    bacteria.  However, in mammalian cells, there is a suggestion of a
    weak clastogenic potential  in vitro but not  in vivo.  Chlorinated
    paraffins are also reported to induce cell transformation  in vitro.

         Long term carcinogenicity studies by oral gavage in rats and mice
    have been conducted on a short chain chlorinated paraffin (C12;
    58% Cl) and a long chain chlorinated paraffin (C23; 43% Cl).  For
    the short chain compound in B6C3F1 mice, there were increases in
    the incidence of hepatic tumours in males and females and tumours of
    the thyroid gland in females. In Fischer-344 rats exposed to the short
    chain compound, there were increases in hepatic tumours in males and
    females, renal tumours (adenomas or adenocarcinomas) in males, tumours
    of the thyroid in females and mononuclear cell leukaemias in males. 
    For the long chain chlorinated paraffin, the incidences of malignant
    lymphomas in male mice and tumours of the adrenal gland in female rats
    were increased.

    1.7  Effects on humans

         In spite of the widespread use of chlorinated paraffins, there
    are no case reports of skin irritation or sensitization.  This is
    supported by results of a limited number of studies in volunteers in
    which chlorinated paraffins have induced minimal irritancy in the
    skin, but not sensitization.

         Data on other effects of chlorinated paraffins in humans have not
    been identified.

    1.8  Effects on other organisms in the laboratory and field

         Chlorinated paraffins of short chain length have been shown to
    be acutely toxic to freshwater and saltwater invertebrates, with
    LC50-EC50 values ranging from 14 to 530 µg/litre.  Most of the acute
    toxicity tests on aquatic invertebrates for intermediate and long
    chain chlorinated paraffins exceed the water solubility.  However, a
    study on an intermediate chlorinated paraffin product shows acute
    toxicity to daphnids at an EC50 of 37 µg/litre.  Short, intermediate
    and long chain chlorinated paraffins appear to be of low acute
    toxicity to fish, with LC50 values well in excess of the water
    solubility.

         Short chain length chlorinated paraffins show long-term toxicity
    to algae, aquatic invertebrates and fish at concentrations as low
    as 19.6, 8.9 and 3.1 µg/litre, respectively; no-observed-effect
    concentrations appear to be in the range of 2 to 5 µg/litre for the
    most sensitive species tested.  An intermediate and a long chain
    product showed chronic effects on daphnids at concentrations of 20 to
    35 µg/litre and < 1.2 to 8 µg/litre, respectively.  Long-term
    toxicity to fish seems to be low.  No data are available on algae.

         On the basis of limited available data, the acute toxicity of
    chlorinated paraffins in birds is low.

    1.9  Evaluation of human health risks and effects on the environment

         It is likely that the principal source of exposure of the general
    population is food.  On the basis of limited data on concentrations
    present in foodstuffs, worst case estimates of daily intake in dairy
    products and mussels, respectively, are 4 and 25 µg/kg body weight
    per day.  In general, the calculated daily intakes of chlorinated
    paraffins are below the tolerable intakes for non-neoplastic effects
    or recommended values for neoplastic effects (short chain compounds).

         Provided that proper personal hygiene and safety procedures are
    followed, the risk to health for workers exposed to chlorinated
    paraffins is expected to be minimal.

         Available data indicate that chlorinated paraffins are
    bioaccumulative and persistent.  The data on environmental levels of
    short chain chlorinated paraffins indicate that in areas close to
    release sources there is a risk to both freshwater and estuarine
    organisms.  There is also a potential risk to aquatic invertebrates
    from intermediate and long chain chlorinated paraffin products.

         The enrichment of chlorinated paraffins in sediments, their
    resorption behaviour and aquatic toxicity indicate a potential risk
    for sediment-dwelling organisms.

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

    2.1  Identity

         Chlorinated paraffins (CPs) are produced by chlorination of
    normal paraffin fractions (straight-chain hydrocarbons, at least 98%
    linear), and have the general formula CxH(2x-y+2)Cly.  The length of
    the carbon chains is usually between 10 and 30 carbon atoms, and the
    chlorine content is between 20 and 70% by weight, although the
    commercial products normally fall within the 40-70% Cl range
    (Schenker, 1979).  In this monograph the different isomers will be
    referred to as Cx;y% Cl, i.e., a chlorinated paraffin with a carbon
    chain length of 12 and a chlorination degree of 60% will be referred
    to as C12;60% Cl.

         Commercial chlorinated paraffins, of which there are over 200,
    are very complex mixtures of  n-alkanes characterized by an average
    carbon chain length and chlorination degree.  Each grade varies in the
    range of carbon chain length, but also in the distribution and degree
    of chlorination.  The different technical grades have therefore
    specific physical and chemical properties which render them useful in
    such widespread applications as plasticizers in plastics such as
    polyvinyl chloride, extreme pressure additives, flame retardants and
    paints.

         The number of theoretically possible structures within the ranges
    C10-C30 and 40-70% Cl is enormous. Taking C12 and 60% Cl as an
    example, there are numerous possibilities, depending on the position
    of the chlorine atoms.  In just one of these structures (Fig. 1),
    there are 25=32 different diastereomers, owing to the five optical
    sites (indicated by an asterisk).

         The raw materials most frequently used for the production of
    chlorinated paraffins are normal paraffin feedstocks, which fall into
    three main categories:

    1) a liquid fraction including C10-C13 with an average of C12;

    2) a liquid fraction including C14-C17 with an average of C15; and

    3) a wax fraction including C20-C28 with an average of C24 (Strack,
    1986).

         A wax fraction including C18-C20 is also used.  Depending on
    the feedstock and the degree of chlorination, long chain length
    chlorinated paraffins (C18-30) range from being mobile to very viscous
    liquids, with the exception of the C20-30;70% Cl type, which is a
    solid.

    CHEMICAL STRUCTURE 1

         In general chlorinated paraffins are classified as short chain
    (C10-13), intermediate chain (C14-17) and long chain (C18-30).  These
    groups are further divided into two classes according to chlorine
    content: < 50% and > 50% chlorine.  A suggested classification of
    the different chlorinated paraffin isomers is shown in Table 1.  The
    suggested acronyms are used in this monograph.

    2.1.1  Relative molecular mass

         The relative molecular mass depends on the carbon chain length
    and the degree of chlorination.  The chlorinated paraffin C10;50.6%
    Cl has a relative molecular mass of 280.1, whereas that of C25;69% Cl
    is 1075.

    2.1.2  Common names

    2.1.2.1  CAS registry number and names

    63449-39-8     Paraffin waxes and hydrocarbon waxes, chloro
    85422-92-0     Paraffin oils and hydrocarbon oils, chloro
    61788-76-9     Alkanes, chloro
    68920-70-7     Alkanes, C6-18, chloro
    71011-12-6     Alkanes, C12-13, chloro
    84082-38-2     Alkanes, C10-21, chloro
    84776-06-7     Alkanes, C10-32, chloro
    84776-07-8     Alkanes, C16-27, chloro
    85049-26-9     Alkanes, C16-35, chloro
    85535-84-8     Alkanes, C10-13, chloro
    85535-85-9     Alkanes, C14-17, chloro
    85535-86-0     Alkanes, C18-28, chloro
    85536-22-7     Alkanes, C12-14, chloro
    85681-73-8     Alkanes, C10-14, chloro
    97659-46-6     Alkanes, C10-26, chloro
    97553-43-0     Paraffins (petroleum), normal C > 10, chloro
    106232-85-3    Alkanes, C18-20, chloro
    106232-86-4    Alkanes, C22-40, chloro
    108171-26-2    Alkanes, C10-12, chloro
    108171-27-3    Alkanes, C22-26, chloro

    FIGURE 2

    2.1.2.2  Synonyms

    Alkanes, chlorinated; alkanes (C10-12), chloro (60%); alkanes (C10-13),
    chloro (50-70%); alkanes (C14-17), chloro (40-52%); alkanes (C18-28),
    chloro (20-50%); alkanes (C22-26), chloro (43%); C12, 60% chlorine;
    C23, 43% chlorine; chlorinated alkanes; chlorinated hydrocarbon
    waxes; chlorinated paraffin waxes; chlorinated waxes; chloroalkanes;
    chlorocarbons; chloroparaffin waxes; paraffin, chlorinated; paraffins,
    chloro; paraffin waxes, chlorinated; paroils, chlorinated; poly-
    chlorinated alkanes; polychloro alkanes.

    2.1.3  Technical products

         Chlorinated paraffins are manufactured commercially by a number
    of companies and are marketed under a variety of trade names.  The
    trade names are followed by numbers, which often are related to the
    average chlorine content (in percent) of a particular preparation. 
    However, this is not a rule and the average chlorine content may have
    to be obtained from manufacturers' technical data.  More than 200
    chlorinated paraffin formulations are commercially available
    world-wide (Serrone et al., 1987), and some examples of these are
    given in Table 2.

         The carbon chain length of the chlorinated paraffins in a
    commercial mixture is variable, and the average chain length is
    usually specified by the manufacturer.  The composition of paraffins
    of different chain length in some commercial formulations is shown in
    Table 3.  The paraffin feedstocks are randomly chlorinated and the
    resulting chlorine contents are given as average values.

         Commercial chlorinated paraffins may be contaminated by
    isoparaffins (usually less than 1%), aromatic compounds (usually less
    than 0.1% (1000 ppm)) and metals (Schenker, 1979).

         Chlorinated paraffins normally contain stabilizers, which are
    added to inhibit decomposition.  Common stabilizers include epoxidized
    compounds such as epoxidized esters and soya bean oils (indicated in
    section 7.1.3 to be present at up to 3%), pentaerythritol, thymol,
    urea, glycidyl ethers, acetonitriles and organic phosphites (Schenker,
    1979; Strack, 1986; Houghton, 1993).  The concentration of stabilizers
    is usually below 0.05% w/w (Campbell & McConnell, 1980).

        Table 2.  Partial list of commercial chlorinated paraffinsa

                                                                                                                                      

    Average molecular formula  C12H15Cl11         C12H19Cl7           C15H26Cl6       C24H29Cl21     C24H42Cl8            C24H44Cl6

    Chlorine content (% w/w)   70                 60-65               50-52           70             48-54                40-42
                                                                                                                                      

    Manufacturers:

    Oxychem, USA               Chlorowax 70L      Chlorowax 500C                      Chlorowax 70   Chlorowax 50         Chlorowax 40

    Keil Chemical Div., USA    CW-200-70          CW-85-60            CW-52                          CW-220-50            CW-170

    Dover Chemical Corp.,      Paroil 170HV       Paroil 160          Paroil 152      Chlorez 700    Paroil 150S          Paroil 140
    USA                                                               Paroil 1048

    Plastifax, Inc., USAb      Plastichlor P-70   Plastichlor P-59                                   Plastichlor 50-220   Plastichlor
                                                  P-65                                                                    42-170

    ICI, Australia; Canada;    Cereclor 70L       Cereclor 60L        Cereclor S52    Cereclor 70    Cereclor 48          Cereclor 42
    UK; France

    Neville Chemical Co.,                         Unichlor 60L-60     Unichlor 50L-65                Unichlor 50-450      Unichlor 40-170
    USAb                                                                                                                  Unichlor 40-150

    Pearsall Chemical Co.,                        FLX-0012            FLX-0008                       CPF-0020             CPF-0004
    USA                                                                                              CPF-0003             CPF-0001

    Hüls AG, Germanyb          Chlorparaffin      Chlorparaffin       Chlorparaffin                                       Chlorparaffin
                               70C                60C                 52G                                                 40N

    Dynamit Nobel, Germanyb    Witaclor 171       Witaclor 160 -      Witaclor 350                   Witaclor 549         Witaclor 540
                                                  Witaclor 163        Witaclor 352

    Caffaro, Italy             Cloparin D70       Cloparin 1059       Cloparin 50     Cloparin S70                        Cloparin P42
                                                                                                                                      

    Table 2.  (Cont'd)

                                                                                                                                      

    Average molecular formula  C12H15Cl11         C12H19Cl7           C15H26Cl6       C24H29Cl21     C24H42Cl8            C24H44Cl6

    Chlorine content (% w/w)   70                60-65              50-52            70             48-54               40-42
                                                                                                                                      

    Hoechst AG, Germany        Chlorparaffin     Hordaflex LC60     Chlorparaffin    Chlorparaffin                      Chlorparaffin
                               Hoechst 70                           Hoechst 52fl     Hoechst 70fest                     Hoechst 40fl

    Rhône-Poulenc, France      Alaiflex 67B2     Ribeclor 60B2      Alaiflex 50A3                                       Alaiflex 40A8
                                                                                                                                      

    a    Other producers include Bann Quimica (Brazil), Excel Industry (India), Ajinomoto (Japan), Tosoh (Japan), Asahi Denka (Japan),
         Plasticlor (Mexico), NCP (South Africa)
    b    These companies have ceased production of chlorinated paraffins.
        Table 3.  Composition of paraffins obtained by dechlorination of
              different chlorinated paraffin preparations (Zitko, 1974b)

                                                                            

    Chlorinated                     Percentage of each paraffin
     paraffin
                                                                            
                      C21    C22    C23    C24    C25    C26    C27    C28
                                                                            

    Chloroparaffin,   4.5    10.0   15.7   19.3   18.5   15.3   9.8    6.7
     40%

    Clorafin 40       3.7    8.2    14.0   17.5   19.2   17.4   12.4   7.6

    CP 40             3.9    9.1    14.9   19.2   19.8   18.0   15.1   -

    Cereclor 42       3.6    8.8    14.7   18.6   19.5   17.2   11.5   6.0

    Chloroparaffin,   7.4    14.9   20.7   23.1   19.9   14.0   -      -
     50%
                                                                            


    2.2  Chemical and physical properties

         Chlorinated paraffins are viscous, colourless or yellowish, dense
    oils, except for the chlorinated paraffins of long carbon chain length
    (C20-C30) with high chlorine content (70%), which are solid. 
    Chlorinated paraffins have a characteristic slight and not unpleasant
    odour (Hardie, 1964).  The odour is probably due to small quantities
    of products of lower relative molecular mass with small but measurable
    vapour pressures (Howard et al., 1975).  Chlorinated paraffins
    themselves have very low vapour pressures.  The medium chain length
    C14-17;52% Cl has a vapour pressure of approximately 2 × 10-4 Pa at
    20°C (1-2 × 10-6 mmHg) (Campbell & McConnell, 1980), and the long
    chain length C23;42-54% Cl approximately 3 × 10-3 Pa when measured at
    65°C (2 × 10-5 mmHg) (Hardie, 1964).  The chemical and physical
    properties of chlorinated paraffins are determined by the carbon chain
    length of the paraffin and the chlorine content.  Increases in the
    carbon chain length and chlorination degree of a particular paraffin
    increase the viscosity and density but reduce the volatility.

         Chlorinated paraffins are practically insoluble in water, but
    many products can be emulsified with water (approximately 70/30
    chlorinated paraffin to water).  The water solubility of 14C-labelled
    polychloroundecane (C11;59% Cl) is reported to be 150-470 µg/litre,

    polychloropentadecane (C15;51% Cl) 5-27 µg/litre and the poly-
    chloropentacosanes (C25;43% Cl) < 5-6.4 µg/litre and (C25;70%
    Cl) < 5-5.9 µg/litre, depending on analytical method (Madeley &
    Gillings, 1983).  Campbell & McConnell (1980) reported the solubility
    of C16;52% Cl to be 10 µg/litre in freshwater and 4 µg/litre in
    seawater.  The solubility of C25;42% Cl was reported to be 3 µg/litre
    in seawater.  Chlorinated paraffins are also practically insoluble in
    lower alcohols, glycerol and glycols, but are soluble in chlorinated
    solvents, aromatic hydrocarbons, ketones, esters, ethers, mineral oil
    and some cutting oils.  They are moderately soluble in unchlorinated
    aliphatic hydrocarbons (Houghton, 1993).  Some physical properties of
    typical commercial chlorinated paraffins are summarized in Table 4.

         Assuming a water solubility of 5 µg/litre and a vapour pressure
    of 2 × 10-4 Pa as typical of a 52% chlorinated intermediate chain
    length paraffin, a Henry's Law constant of 10.9 may be calculated
    (Willis et al., 1994).

         A key property of chlorinated paraffins, particularly the high
    chlorine grades, is their nonflammability. This is due to the ability
    of chlorinated paraffins to release hydrochloric acid at elevated
    temperatures, and the hydrochloric acid inhibits the radical reaction
    in a flame.  This property is considerably enhanced by the addition of
    antimony trioxide (Houghton, 1993) or other additives.  Chlorinated
    paraffins are generally unreactive and stable in normal temperatures,
    but decompose significantly at temperatures above 300°C with the
    release of hydrochloric acid (Strack, 1986).  Prolonged exposure
    to light can also cause dehydrochlorination.  Degradation by
    dehydrochlorination can be accelerated at elevated temperatures in
    the presence of aluminium, zinc, and iron oxide or chloride (Howard
    et al., 1975; Houghton, 1993).  Dehydrochlorination leads to darkening
    of the material.

    2.3  Analysis

         The analysis of chlorinated paraffins is very difficult owing to
    the many congeners present in the products.  The properties of these
    congeners cover wide ranges, which makes it difficult to separate the
    chlorinated paraffins from other compounds that may interfere in the
    analysis.

        Table 4.  Physical properties of selected commercial chlorinated paraffinsa

                                                                                                                                      

    Paraffin      Chlorine   Colour hazen   Viscosityb    Densityb   Thermal stabilityc   Volatilityd   Refractive    Log Powe
    feedstock     content    (APHA)         (Pa.s)        (g/ml)     (% w/w HCl)          (% w/w)       index
                  % (w/w)
                                                                                                                                      

    C10-C13       50         100            0.08          1.19       0.15                 16.0          1.493         4.39-6.93
                  56         100            0.8           1.30       0.15                 7.0           1.508         NRg
                  60         125            3.5           1.36       0.15                 4.4           1.516         4.48-7.38
                  63         125            11.0          1.41       0.15                 3.2           1.522         5.47-7.30
                  65         150            30.0          1.44       0.20                 2.5           1.525         NR
                  70         200            8.0f          1.50       0.20                 0.5           1.537         5.68-8.01h

    C14-C17       40         80             0.07          1.10       0.2                  4.2           1.488         NR
                  45         80             0.2           1.16       0.2                  2.8           1.498         5.52-8.21
                  52         100            1.6           1.25       0.2                  1.4           1.508         5.47-8.01
                  58         150            40.0          1.36       0.2                  0.7           1.522         NR

    Wax C18-C20   47         150            1.7           1.21       0.2                  0.8           1.506         NR
                  50         250            18.0          1.27       0.2                  0.7           1.512         NR

    Wax (C> 20)   42         250            2.5           1.16       0.2                  0.4           1.506         9.29->12.83h
                  48         300            28.0          1.26       0.2                  0.3           1.516         8.69-12.83
                  70         100i           j             1.63       0.2                  NR            -             NR
                                                                                                                                      

    a    Data from Houghton (1993)                                                  f    At 50°C
    b    At 25°C unless otherwise noted                                             g    NR = not reported
    c    Measured in a standard test for 4 h at 175°C                               h    Data from Cereclor 42
    d    Measured in a standard test for 4 h at 180°C                               i    10 g in 100 ml toluene solvent
    e    Octanol:water partition coefficients. From: Renberg et al (1980)           j    Solid, softening point = 95-100°C
        2.3.1  Sampling

         To prevent contamination by trace amounts of chlorinated
    paraffins, samples or their extracts must not be allowed to come into
    contact with any plastic (especially PVC) container, stopper, cap
    liner or tubing, because these may contain chlorinated paraffins
    (Hollies et al., 1979).  All solvents should be rigorously tested
    before use, and it is recommended that glass distilled solvents are
    used.  All glassware should be decontaminated before use by heating at
    250°C for 24 h.  Water and sediment samples should be stored at
    ambient temperatures, and should be analysed within a month of
    sampling.

         Treatment of samples for the extraction of chlorinated paraffins
    is described in Table 5.

    2.3.2  Analytical methods

         Methods used for detection of chlorinated paraffins in various
    samples are shown in Table 5.

         Hollies et al. (1979) determined C13-17 and C20-30 chlorinated
    paraffin after clean-up of the samples on aluminium oxide columns. 
    The chlorinated paraffin fraction was then applied on a silica gel
    thin-layer chromatography (TLC) plate.  After forward elution with
     n-hexane and subsequently with toluene, and backward elution with
     n-hexane, chloride from the chlorinated aliphatics was transferred
    to an aluminium oxide plate at 240°C and developed with silver
    nitrate.  The resulting spots were quantified by visual comparison
    with spots of known amounts of reference materials.  Although the
    procedure is complicated and involves several evaporations to dryness,
    good recoveries were reported. Possible interference from a number of
    other chlorinated compounds was investigated and found to be
    negligible, but the method must still be regarded as fairly
    non-specific.

         Gas chromatographic analysis of chlorinated paraffin, using
    microcoulometric detection, has been described by Zitko (1973).  This
    method gives badly resolved chromatograms and there is a considerable
    risk of interference from other halogenated compounds. Owing to high
    temperatures in the gas chromatographic system there is also a risk of
    dehydrochlorination of the chlorinated paraffin congeners.  In a later
    study (Zitko & Arsenault, 1977), interference from other compounds was
    avoided by a solvent partitioning clean-up procedure.

        Table 5.  Analytical methods for the determination of chlorinated paraffins in various samplesa

                                                                                                                                      

    Sample       Preparation method                                       Analytical  Sample detection  Recovery         Reference
    matrix                                                                methodb     limitb
                                                                                                                                      

    Water        Extract with petroleum spirit; concentrate; purify by    TLC         500 ng/litre      90%              Hollies et
                 aluminium oxide chromatography, elute with toluene;                                                     al. (1979)
                 dry; dissolve in petroleum spirit

    Water        Extract with hexane; purify by aluminium oxide           GC/ECD      3 ng/litre        NR               Kraemer &
                 chromatography; elute with hexane/dichloromethane                                                       Ballschmiter
                 (4%); purify by silica gel chromatography, elute with                                                   (1987)
                 hexane:dichloromethane (19:1); dissolve in isooctane.

    Water        Extraction with hexane (particle phase Soxhlet           GC/         approx.           92-120%          Steele et
                 extracted), silica gel and aluminium oxide column        MS-NCI      1 µg/litre                         al. (1988)
                 chromatography

    Biological   Homogenize; extract with petroleum spirit:acetone        TLC         50 µg/kg          80-90%           Hollies et
     material    (2:1); dry; dissolve in petroleum spirit; extract with                                                  al. (1979)
                 dimethylformamide; wash; back-extract with Na2SO3
                 solution and petroleum spirit; purify by silica gel
                 chromatography, elute with CCl4; dry; dissolve in
                 acetone; extract with petroleum spirit:acetone (1:4)

    Cod muscle   Homogenize in n-hexane:acetone (1:2.5, v:v); extract     GC/MS       NR                98-114% at       Jansson et
     tissue      with 10% diethyl ether in n-hexane; evaporate; dissolve                                0.465 µg/sample  al. (1991)
                 in dichloromethane:n-hexane (1:1, v/v); purify by gel                                  and 89-92% at
                 permeation chromatography; concentrate; extract with                                   2.33 µg/sample
                 sulfuric acid; concentrated in organic phase

    Adipose      Homogenize in dichloromethane; percolate through         GC/MS       5 ng              80%              Schmid &
     tissue      anhydrous Na2SO4; remove solvent; dissolve residue in                                                   Müller (1985)
                 pentane; wash, dry and concentrate; purify by alumina
                 chromatography
                                                                                                                                      

    Table 5.  (Cont'd)

                                                                                                                                      

    Sample          Preparation method                                      Analytical  Sample detection   Recovery   Reference
    matrix                                                                  methodb     limitb
                                                                                                                                      

    Mineral oil     Extract fish in cyclohexane; introduce extract or       MS-NCI      NR                 NR         Gjos &
     and fish       mineral oil sample directly into mass spectrometer                                                Gustavsen
     extract                                                                                                          (1982)

    Fish fillets    Homogenize in petroleum ether; clean-up by irradiating  GC/CD       NR                 > 90%      Friedman &
                    extracts with high-intensity UV light (90 min, < 20°C)                                            Lombardo
                    in petroleum ether                                                                                (1975)

    Sewage          Homogenize in acetone; extract with pentane; wash, dry  GC/MS       5 ng               NR         Schmid &
     sludge         and concentrate; purify by alumina chromatography                                                 Müller (1985)

    Sediment        Dry at 70°C; extract with petroleum spirit;             TLC         50 µg/kg           80%        Hollies et
                    concentrate; purify by aluminium oxide                                                            al. (1979)
                    chromatography, elute with toluene; dry; dissolve
                    in petroleum spirit

    Sediment        Extract with acetone:hexane (1:1, v:v); wash, dry       GC/MS       5 ng               NR         Schmid &
                    and concentrate; purify by alumina chromatography                                                 Müller (1985)

    Sediment        Soxhlet extraction with hexane, silica gel and          GC/         approx.            52-64%     Steele et
                    aluminium oxide column chromatography                   MS-NCI      1 µg/litre                    al. (1988)
                                                                                                                                      

    a    Modified from IARC (1990)
    b    GC/MS = gas chromatography/mass spectrometry; GC/CD = gas chromatography/coulometric detection;
         GC/ECD = gas chromatography/electron capture detection; MS-NCI = negative-ion chemical ionization mass spectrometry;
         TLC = thin-layer chromatography; NR = not reported
             Attempts have been made to reduce the complexity of chlorinated
    paraffin mixtures by reductive dechlorination (Cooke & Roberts, 1980;
    Roberts et al., 1981; Sistovaris & Donges, 1987).  This method gives
    information on the "carbon skeleton" of the chlorinated paraffin
    compounds but no information on the chlorine content, and it is
    difficult to separate the response from that of unchlorinated
    hydrocarbons.

         Negative ion chemical ionization mass spectrometry (MS-NCI) was
    used by Gjös & Gustavsen (1982).  In this method the chlorinated
    paraffin fractions are introduced directly into the ion source of the
    mass spectrometer.  As the whole sample is analysed in a very short
    time, the concentration in the ion source is high and the sensitivity
    can therefore be high.  A serious disadvantage is that all other
    compounds in the sample come into the mass spectrometer at the same
    time, the risk of interference is high and an extensive clean-up of
    the samples is needed.

         Gas chromatography utilizing MS-NCI for the detection was used by
    Schmid & Müller (1985).  A fairly simple clean-up based on adsorption
    chromatography on aluminium oxide was used, but unfortunately this
    has been impossible to reproduce (Jansson, personal communication). 
    GC/MS-NCI was also used by Steele et al. (1988) to determine
    chlorinated paraffins after clean-up of samples on silica gel and
    aluminium oxide columns.  They used low inlet temperatures in the
    gas chromatograph to avoid thermolysis of the analysed compounds.

         The use of low temperatures and short capillary columns further
    decreases the risk of temperature-related break-down of chlorinated
    paraffins during gas chromatographic analysis (Jansson et al., 1991). 
    In this method a gel permeation column was also used to avoid
    interference from other chlorinated compounds, and the Cl2- and
    HCl2- ions were used to detect aliphatic chlorinated compounds
    selectively.

         Developments in chlorinated paraffin analysis have improved
    both selectivity and sensitivity.  However, although the reliability
    of results is now better, these are only estimates of the real
    concentrations as it is impossible to detect the individual substances.

    3.  SOURCES OF HUMAN AND ENVIRONMENTAL EXPOSURE

    3.1  Natural occurrence

         Chlorinated paraffins are not known to occur naturally.

    3.2  Anthropogenic sources

    3.2.1  Production levels and processes

         Liquid chlorinated paraffins were first used in large amounts
    during the period 1914-1918 as solvents for Dichloramine T in
    antiseptic nasal and throat sprays (Howard et al., 1975).  The
    commercial production of chlorinated paraffins for use as extreme
    pressure additives in lubricants started around 1930 (Schenker, 1979).

         Estimated data on the production of chlorinated paraffins are
    shown in Table 6. Chlorinated paraffins are produced in Australia,
    Brazil, Bulgaria, Canada, China, Germany, France, India, Italy, Japan,
    Mexico, Poland, Romania, Spain, Slovakia, South Africa, China
    (Province of Taiwan), Thailand, the United Kingdom, the USA, and the
    former USSR.  However, this may not be a complete list of producer
    countries.  It is believed that 50% of the chlorinated paraffins
    produced in the world have carbon chain lengths of between 14 and 17
    and a chlorine content of between 45 and 52%. In the United Kingdom
    approximately 80% of the total production of chlorinated paraffins is
    concentrated on the C14-17 chain length.  About 15% of the European
    consumption of chlorinated paraffins is estimated to be C10-13, 70%
    C14-17 and 15% C20-30 (Willis et al., 1994).

         Chlorinated paraffins are produced by reacting liquid paraffin
    fractions obtained from petroleum distillation with pure chlorine gas
    by a reaction mechanism involving free radicals (Schenker, 1979;
    Houghton, 1993).  The reaction is exothermic.  At a chlorine content
    above approximately 54% further chlorination is slow and difficult. 
    In the production of resinous chlorinated paraffins containing
    > 70% Cl, a solvent is usually added to decrease the viscosity
    (Howard et al., 1975).  Carbon tetrachloride has been the most
    commonly used solvent, and may be present in trace amounts in the
    final product, although alternative production methods are being
    developed because of the phase-out of carbon tetrachloride under the
    Montreal Protocol (D. Farrer, personal communication to the IPCS,
    1995).

         The substituted chlorine atoms are probably randomly distributed,
    and at a chlorination of 72% all of the carbon atoms are singly
    chlorinated.  Further chlorination is difficult since the first
    chlorine substitution decreases the reactivity of the other hydrogens
    on a particular carbon atom (Hardie, 1964).

    Table 6.  Estimated production of chlorinated paraffins

                                                                             

                                 Production        References
                                 (tonnes/year)
                                                                             

    Canada - 1990                2900              Camford Information
                                                   Services (1991)
    Germany - 1990/1991          20 000-30 000     BUA (1992)
    United Kingdom - 1992        50 000            Willis et al. (1994)
    USA - 1977                   37 000            Schenker (1979)
    USA - 1983                   45 000            NTP (1986a)
    USA - 1987                   45 000            IARC (1990)
    USA - 1990                   26 000            US EPA (1993)
    North America - 1978         60 000            Zitko (1980)
    Western Europe - 1978        105 000           Zitko (1980)
    Western Europe - 1985        95 000            IARC (1990)
    World, excluding             230 000           Campbell &
     Eastern Europe - 1977                         McConnell (1980)
    World - 1985a                300 000           Strack (1986)
                                                                             

    a    Excluding the former Soviet Union and the People's Republic of China.

         Depending on producer and paraffin feedstock, the temperature of
    the chlorination reaction is usually kept at 80-100°C to decrease the
    viscosity but at a temperature where the decomposition of the product
    is not extensive (Schenker, 1979; Houghton, 1993).  Since the reaction
    is exothermic heat removal is important in the process.  Ultraviolet
    light is often used as a catalyst (Schenker, 1979; Houghton, 1993). 
    Metal catalysts are avoided since they may promote dechlorination of
    the chlorinated paraffins.  Since for each tonne of chlorinated
    paraffin produced, approximately half a tonne of hydrochloric acid is
    generated, the linings of the reactor vessels must be chemically inert
    to avoid the formation of metal chlorides, which cause darkening of
    the product by decomposition (Strack, 1986; Houghton, 1993). 
    Additional procedures used in the production of the C20-30;70% Cl solid
    grade are stripping of the solvent and grinding of solid products
    (Schenker, 1979).

    3.2.2  Uses

         Chlorinated paraffins are used as secondary plasticizers for
    polyvinyl chloride (PVC) and can partially replace primary
    plasticizers such as phthalates and phosphate esters (Houghton, 1993). 
    The use of chlorinated paraffins has the advantage in comparison with
    conventional plasticizers of both increasing the flexibility of
    the material as well as increasing its flame retardancy and

    low-temperature strength (Howard et al., 1975).  Chlorinated paraffins
    are also used as extreme pressure additives in metal-machining fluids
    or as metal-working lubricants or cutting oils because of their
    viscous nature, compatibility with oils, and property of releasing
    hydrochloric acid at elevated temperatures.  The hydrochloric acid
    reacts with metal surfaces to form a thin but strong solid film of
    metal chloride lubricant.  In Sweden, the use of chlorinated paraffins
    in metal-working fluids has been reduced from 680 tonnes (1986) to
    139 tonnes (1993) as a part of a risk reduction programme (Swedish
    Environmental Protection Agency, 1994).  They are added to paints,
    coatings and sealants to improve resistance to water and chemicals,
    which is most suitable when they are used in marine paints, as
    coatings for industrial flooring, vessels and swimming pools (e.g.,
    rubber and chlorinated rubber coatings), and as road marking paints. 
    The flame-retarding properties of highly chlorinated paraffins make
    them important as additives in plastics, fabrics, paints and coatings. 
    The most effective fire-retardant action is obtained with a high
    degree of chlorination.

         By the late 1970s approximately 50% of chlorinated paraffins in
    the USA was used as extreme pressure lubricant additives in the
    metal-working industry; 25% was used in plastics and fire-retardant
    and water-repellant fabric treatments, and the rest was used in paint,
    rubber, caulks and sealants (Schenker, 1979).  In the United Kingdom,
    65-70% of the consumed chlorinated paraffins is used as a secondary
    plasticizer in PVC, about 10% in paint, about 10% in metal-cutting
    lubricants and about 10% in flame retardants and sealants (Willis et
    al., 1994).  In Canada approximately 55% of the chlorinated paraffins
    is used as plasticizers and 35-40% as high-pressure lubricant
    additives (Camford Information Services, 1991).  Some examples of
    applications for chlorinated paraffins of different chain-lengths are
    shown in Table 7.

    3.2.3  Loss into the environment

         Since chlorinated paraffins are produced without contact with
    water, the possibility of leakage into the environment by direct water
    discharge is low.  After chlorination the solvent is removed and
    residual amounts of chlorine gas and hydrogen chloride are removed by
    blowing air or other gases through the product.  This could possibly
    lead to some loss into the air, but since the chlorine gas and
    hydrochloric acid are recovered and the volatility of chlorinated
    paraffins is very low, the loss is likely to be very low (Howard et
    al., 1975).  Emission into the atmosphere during manufacture in
    Germany in 1990 was estimated to be about 250 kg/year (BUA, 1992). It
    is possible that chlorinated paraffins may be a by-product during
    chlorination of other hydrocarbon feedstocks if paraffins are present
    as contaminants.  This could lead to possible environmental
    contamination.

        Table 7.  Uses of various chlorinated paraffins

                                                                                                

    Paraffin        Chlorination (%)       Application
    feedstock
                                                                                                

    C10-13                                 plasticizer for PVC or plastics

    C10-13                                 metal-working fluids; sealants

    C10-13          approx. 70             flame retardants for rubber and soft plastics

    C14-17          40-60                  extreme pressure additives to metal-machining
                                           fluids, pastes, emulsions and lubricants

    C14-17          45-52                  the chlorinated paraffin most frequently used as a
                    (40-50)                plasticizer for plastics; also used for sealants

    C18-30          approx. 70             flame retardants for rigid plastics such
                                           as polyesters and polystyrene

    C> 20                                  plasticizer for PVC or plastics
                                                                                                
    
         Some loss into the environment could be expected during transport
    and storage.  If the drums which are used for the transport of
    chlorinated paraffins are cleaned for further use environmental
    release might occur.  Soil could be contaminated if empty drums are
    dumped at landfills.  Spills may occur, but clean-up using an
    adsorbent material is easy.  The adsorbent material would probably
    be deposited in a landfill, which in turn could lead to possible
    environmental contamination.

         The uses of chlorinated paraffins probably provide the major
    source of environmental contamination.  When chlorinated paraffins are
    used as plasticizers or additives in coatings, they are effectively
    dissolved in the polymers and will therefore leak into the environment
    only very slowly.  However, polymers containing chlorinated paraffins
    will act as sources of chlorinated paraffins for centuries after
    disposal.  A more likely route of leakage of chlorinated paraffins
    into the environment would be the improper disposal of oils containing
    chlorinated paraffins (Campbell & McConnell, 1980) or disposal of
    chlorinated paraffins of low quality (Howard et al., 1975).  Loss of
    chlorinated paraffins by removal from paints and coatings may also
    contribute to environmental contamination.

         It is estimated that a maximum of 55% of the cutting and
    lubricating oils sold to the engineering industry in Sweden becomes
    waste.  The rest is consumed or released into the air and water (KEMI,
    1991).  The largest consumer of chlorinated paraffins in Sweden
    (1400 tonnes/year) has estimated its emission of chlorinated paraffins
    to be 90 kg/year (0.06 g emission/kg chlorinated paraffin produced)
    (KEMI, 1991).

         Disposal of wastes containing chlorinated paraffins occurs
    through resource recovery, destructive incineration or landfill,
    usually on disposal sites for special wastes and in compliance with
    local regulations.  Owing to their thermal instability, chlorinated
    paraffins are expected to be degraded by incineration at low
    temperatures and thus would not be expected to volatilize in exhaust
    gases from an incinerator.  However, in a study by Bergman et al.
    (1984), chlorinated aromatic compounds such as PCBs, naphthalenes and
    benzenes were formed by pyrolysis of chlorinated paraffins (see
    section 4.2.1) although the conditions used were not identical to the
    operation conditions of waste incineration plants.  Chlorinated
    paraffins are not expected to be formed  de novo.  The disposal of
    chlorinated paraffins in landfills may give rise to leaching into
    water, but owing to the low water solubility and strong adsorption
    onto solids the amounts reaching water are likely to be low.

    4.  ENVIRONMENTAL TRANSPORT, DISTRIBUTION AND TRANSFORMATION

    4.1  Transport and distribution between media

         Considering the low vapour pressure (2 × 10-4 Pa at 20°C for
    C14-17;52% Cl to 3 × 10-3 Pa at 65°C for C23;42-54% Cl), low water
    solubility (3 to 470 µg/litre) and highly lipophilic nature of
    chlorinated paraffins (log Pow values range from 4.39 to > 12.83),
    it is likely that they will distribute mainly to the soil/sediment
    phase with very little volatilization occurring.  Chlorinated
    paraffins are likely to be transported in water as suspended
    particles, and in air as dust particles and possibly in the vapour
    phase.  However, no experimental data on this subject have been
    reported.

    4.2  Transformation

    4.2.1  Abiotic transformation

         No experimental data on the chemical stability of chlorinated
    paraffins under simulated environmental conditions have been reported. 
    However, their chemical reactivities suggest that they do not
    hydrolyse, oxidize or react by other mechanisms at significant rates
    under normal temperatures and neutral conditions (Howard et al.,
    1975).  Dehydrochlorination of chlorinated paraffins may possibly
    occur naturally in the presence of metal ion contamination.

         Because of the high adsorption tendency of chlorinated paraffins,
    gas phase reactions are assumed to contribute only little to
    degradation in the atmosphere (BUA, 1992).  However, calculated
    half-lives for chlorinated paraffins in air are reported to range from
    0.85 to 7.2 days (Slooff et al., 1992).  The theoretical values are
    shown in Table 8.

         The thermal degradation by pyrolysis of chlorinated paraffins at
    various temperatures (300, 500, 700°C) and times (10 sec to 20 min)
    was studied by Bergman et al. (1984).  The chlorinated paraffins were
    totally degraded, and, depending upon degree of chlorination of the
    chlorinated paraffin, several aliphatic and aromatic degradation
    products, such as polychlorinated biphenyls (PCBs), naphthalenes and
    benzenes, were detected. As much as 10 g of PCBs per kg chlorinated
    paraffin could be found after thermal degradation of C12;70% Cl
    (temperature not specified).  Smaller amounts of compounds were formed
    at lower temperatures.  Considering these results, processes where
    chlorinated paraffins are subjected to temperatures above 300°C could
    lead to environmental contamination and exposure to more persistent
    and toxic substances than the original chlorinated paraffins.


        Table 8.  Photochemical degradation of chlorinated paraffins in the
              atmosphere (From: Slooff et al., 1992)

                                                                             

    Carbon chain length      Koh (cm3/mol per sec)      Half-life (days)
                                                                             

    C10-C13                  9.0-14.9 × 10-12           1.2-1.8

    C14-C17                  14.9-18.9 × 10-12          0.85-0.8

    C15-C30                  20.2-31.1 × 10-12          0.5-0.8

    not specified            2.2-18.8 × 10-12           0.85-7.2
                                                                             
    
    4.2.2  Biodegradation

         Chlorinated paraffins are generally stable in the natural
    environment.

    4.2.2.1  Short chain length chlorinated paraffins

         A short chain length paraffin (C10-12) with 58% chlorination
    (CP-SH) was not readily biodegraded by activated sludge, under either

    aerobic or anaerobic conditions, over a 28-day period in an inherent
    biodegradability (modified Zahn-Wellens) test (Street & Madeley,
    1983a,b) or a 51-day period in a coupled units test (Mather et al.,
    1983).

    4.2.2.2  Long chain length chlorinated paraffins

         Zitko & Arsenault (1977) studied sediment spiked with 596 mg/kg
    dry weight of Cereclor 42 C24;42% Cl, CP-LL) or 357 mg/kg dry weight
    of Chlorez 700 (C24;70% Cl, CP-LH), which are both long chain length
    chlorinated paraffins but have different chlorine contents.  There was
    no clear trend in the results but they indicated that after 4 weeks
    the highly chlorinated Chlorez 700 was degraded to a greater extent
    than Cereclor 42.  The rate of degradation seems to have been higher
    under anaerobic conditions.

    4.2.2.3  Comparative studies

         In another study, the microbial degradation of several short,
    intermediate and long chain length chlorinated paraffins of different
    chlorination degree at concentrations of 2, 10 and 20 mg/litre was
    examined in a 25-day biochemical oxygen demand (BOD) test (Madeley &

    Birtley, 1980).  The degradation rate appeared to decrease with
    increasing carbon chain length and chlorination degree, and the short
    chain chlorinated paraffins with less than 50% Cl were degraded most
    rapidly and completely.  It can be concluded from the results that
    chlorinated paraffins with low chlorine contents (< 50% wt Cl) and,
    especially, short chain chlorinated paraffins, biodegrade slowly in
    the environment, particularly in the presence of adapted microbial
    populations, but that chlorinated paraffins with higher chlorine
    contents are unlikely to biodegrade under aerobic conditions. 
    Anaerobic microorganisms did not degrade Cereclor 42 (C24;42% Cl) in
    30 days when readily biodegradable alternative carbon sources were
    available.

         Omori et al. (1987) found that bacterial strains isolated from
    the soil degraded various chlorinated paraffins by dechlorination in
    the presence of  n-hexadecane. In a mixed culture of four strains,
    more than 50% of the chlorine was removed from the shorter paraffins
    with lower chlorine content (C14;43% Cl, CP-ML and C15;50% Cl, CP-MH)
    within 36 h.  Lower amounts of chlorine were removed from the
    chlorinated paraffins with longer chain lengths.  Activated sludge
    from a sewage treatment plant in Tokyo acclimatized to  n-hexadecane
    for 60 days showed only a limited amount (2%) of dechlorination of the
    chlorinated paraffins.  The bacterial dechlorination concerned the
    terminal chlorine, which produced 2- or 3-chlorinated fatty acids via
    ß-oxidation.

    4.3  Bioaccumulation and biomagnification

    4.3.1  Summary

         Chlorinated paraffins of short chain length accumulate in mussels
    and fish to a higher degree than intermediate and long chain length
    chlorinated paraffins.

         Data on bioaccumulation of chlorinated paraffins by aquatic
    organisms are summarized in Table 9.  Bioconcentration factors (BCFs)
    may be uncertain since the applied doses exceeded the water solubility
    in several experiments.

        Table 9.  Bioconcentration factors for some chlorinated paraffins

                                                                                                                                      

    Species                       Chlorinated paraffina            Exposure          Bioconcentration   Reference
                                                          Concentration   Duration   factor
                                                          (µg/litre)      (days)     (whole animal)b
                                                                                                                                      

    Marine diatom                 C10-12;58% Cl (CP-SH)   1.4             10         < 1                Thompson & Madeley (1983b)
     (Skeletonema costatum)                               17.8            10         3.5

    Freshwater green alga         C10-12;58% Cl (CP-SH)   35              10         1.5                Thompson & Madeley (1983d)
     (Selenastrum capricornutum)                          140             10         7.6
                                                          150             10         4.1

    Mussel                        C10-12;58% Cl (CP-SH)   2.3             147        40 900e            Madeley et al. (1983a)
     (Mytilus edulis)                                     10              91         24 800e

                                  C10-12;58% Cl (CP-SH)   13              60         25 292e            Madeley & Thompson (1983a)
                                                          130             60         12 177e

                                  C12;69% Cl (CP-SH)      0.13            28         138 000e           Renberg et al. (1986)
                                  C16;34% Cl (CP-ML)      0.13            28         6920e

                                  C14-17;52% Cl (CP-MH)   220             60         2856e              Madeley & Thompson (1983b)
                                                          3800c           60         429e

                                  C22-26;43% Cl (CP-LL)   120             60         1158e              Madeley & Thompson (1983c)
                                                          2180c           60         261e

                                  C22-26;70% Cl (CP-LH)   460             60         341e               Madeley & Thompson (1983d)
                                                          1330c           60         223e
                                                                                                                                      

    Table 9.  (Cont'd)

                                                                                                                                      

    Species                       Chlorinated paraffina            Exposure          Bioconcentration   Reference
                                                          Concentration   Duration   factor
                                                          (µg/litre)      (days)     (whole animal)b
                                                                                                                                      

    Rainbow trout                 C10-12;58% Cl (CP-SH)   3.1             168        3550e              Madeley & Maddock (1983b)
     (Oncorhynchus mykiss)                                14              168        5260e

                                  C10-12;58% Cl (CP-SH)   33              60         7155e              Madeley & Maddock (1983c)
                                                          3050c           60         1173e

                                  C14-17;52% Cl (CP-MH)   1050c           60         45e                Madeley & Maddock (1983c)
                                                          4500c           60         67e

                                  C22-26;43% Cl (CP-LL)   970             60         18e                Madeley & Maddock (1983c)
                                                          4000c           60         38e

                                  C20-30;70% Cl (CP-LH)   840             60         54e                Madeley & Maddock (1983c)
                                                          3800c           60         32e

    Bleaks                        C10-13;49% Cl (CP-SL)   125             14         770d,f             Bengtsson et al. (1979)
     (Alburnus alburnus)                 59% Cl (CP-SH)   125             14         740d,f             Bengtsson et al. (1979)
                                         71% Cl (CP-SH)   125             14         140d,f             Bengtsson et al. (1979)

                                  C14-17;50% Cl (CP-MH)   125             14         30d,f              Bengtsson et al. (1979)
                                  C18-26;49% Cl (CP-LL)   125             14         7d,f               Bengtsson et al. (1979)
                                                                                                                                      

    a    The classification of chlorinated paraffins is given in Table 1
    b    Ratio of the concentration of the chemical in the organism to the concentration of the chemical in the environment or food
    c    May exceed water solubility
    d    BCFs calculated by Zitko (1980)
    e    BCFs based on radioactivity (14C)
    f    BCFs based on parent compounds
        4.3.2  Aquatic vertebrates

    4.3.2.1  Short chain length chlorinated paraffins

         In a study by Lombardo et al. (1975), fingerling rainbow trout
     (Oncorhynchus mykiss) were fed a diet containing 10 mg/kg Chlorowax
    500C (C12;60% Cl, CP-SH) for 82 days.  Samples of 20 exposed and 10
    control fish were collected at approximately 2-week intervals during
    the time-period and analysed for chlorinated paraffin content by
    microcoulometric gas chromatography (Friedman & Lombardo, 1975).  The
    tissue level of chlorinated paraffins rose during the treatment period
    to 1.1 mg/kg (on tissue basis) or 18 mg/kg (on fat basis) after 82
    days (detection level: 0.5 mg/kg).  The experiment had to be
    terminated owing to the failure of the water supply, and it was not
    possible to determine whether a steady-state level had been reached.

         In studies (Madeley & Maddock, 1983b) on rainbow trout
     (Oncorhynchus mykiss) exposed to measured concentrations of 3.1 and
    14.3 µg/litre of 14C-labelled C10-12; 58% Cl (CP-SH) for a period of
    168 days, BCF value of 1300 (low dose) and 1600 (high dose) were
    observed in the flesh, 2800 (low dose) and 16 000 (high dose) in the
    liver, and 11 700 (low dose) and 15 500 (high dose) in the viscera;
    all values were determined from radioactivity measurements.  The BCF
    for the whole body was 3350 (low dose) and 5260 (high dose)
    (calculated values).  Half-lives for elimination in different organs
    were calculated to be the following: liver 9.9 (low dose) and 11.6
    days (high dose), viscera 23.1 (low dose) and 23.9 days (high dose),
    and flesh 16.5 (low dose) and 17.3 days (high dose).

         Rainbow trout  (Oncorhynchus mykiss) were exposed to measured
    concentrations ranging from 33 to 3050 µg/litre of C10-12;58% Cl
    (CP-SH) for 60 days (Madeley & Maddock, 1983c).  BCFs, which were
    determined in whole fish samples at the end of the test, were 7155
    (low dose) and 1173 (high dose) based on radioactivity measurements,
    and 7273 (low dose) and 574 (high dose) based on parent compound
    analysis.  Parent compound analysis was performed using a modification
    of the method of Hollies et al. (1979) (see section 2.3.2).

    4.3.2.2  Intermediate chain length chlorinated paraffins

         After 60 days exposure of rainbow trout  (Oncorhynchus mykiss)
    to measured concentrations of 1050 and 4500 µg/litre of intermediate
    length (C14-17) chlorinated paraffins with 52% Cl (CP-MH), whole body
    BCFs of 45 (low dose) and 67 (high dose) based on radioactivity
    measurements, and of 32 (low dose) and 42 (high dose) based on parent
    compound analysis were determined (Madeley & Maddock, 1983c).  The
    BCFs were determined at the end of the exposure period.  Parent
    compound analysis was performed using a modification of the method of
    Hollies et al. (1979) (see section 3.2.3).

    4.3.2.3  Long chain length chlorinated paraffins

         Juvenile Atlantic salmon  (Salmo salar) were exposed to Cereclor
    42 (C24;42% Cl, CP-LL) or Chlorez 700 (C24;70% Cl, CP-LH) by uptake
    from suspended solids or from food (Zitko, 1974a).  The fish were
    treated with either 1000 µg/litre of contaminated suspended solids for
    48 h and 144 h, or to 10 mg/kg or 100 mg/kg of contaminated food for
    181 days with a subsequent elimination period of 74 days.  No or very
    low accumulation of the chlorinated paraffins was observed.  However,
    the analytical method used determined the amount of chlorine and not
    of chlorinated paraffin; this method has been considered as nonspecific
    and of low sensitivity.

         After 60 days exposure of rainbow trout  (Oncorhynchus mykiss)
    to long chain chlorinated paraffins with 43% Cl (CP-LL) (970 or
    4000 µg/litre) or 70% Cl (CP-LH) (840-3800 µg/litre), whole body BCFs,
    based on measured exposure concentrations, of 17.9 (low dose, 43% Cl),
    37.6 (high dose, 43% Cl) and 53.8 (low dose, 70% Cl) and 32.5 (high
    dose, 70% Cl) were determined at the end of the study when measured as
    radioactivity.  BCF values of 3.6 (low dose, 43% Cl), 9.0 (high dose,
    43% Cl), 42.8 (low dose, 70% Cl) and 31.6 (high dose, 70% Cl), based
    on parent compound analysis, were determined (Madeley & Maddock,
    1983c).

    4.3.3  Aquatic invertebrates

    4.3.3.1  Short chain length chlorinated paraffins

         After 60 days exposure of mussels  (Mytilus edulis) to a short
    chain length paraffin with 58% Cl (CP-SH) at measured concentrations
    of 13 and 130 µg/litre, whole body BCFs were 25 292 and 12 177,
    respectively, based on radioactivity measurements, and 20 000 and
    7923 when measured as parent compound (Madeley & Thompson, 1983a).

         After exposure of mussels  (Mytilus edulis) for 147 days to
    14C-labelled short chain length chlorinated paraffin with 58% Cl
    (CP-SH) followed by a depuration period of 98 days (measured exposure
    dose: 2.3 µg/litre), or for 91 days followed by 84 days of depuration
    (measured exposure dose: 10.1 µg/litre), plateau levels of the
    chlorinated paraffin in tissues were reached.  Bioconcentration
    factors (BCFs) at the plateau levels were 40 900 for whole mussel
    tissue after exposure to 2.35 µg/litre and 24 800 after exposure to
    10.1 µg/litre based on wet tissue basis.  Of the different organs the
    digestive glands had the highest BCF values of 226 000 (low exposure)
    and 104 000 (high exposure).  Half-lives for the chlorinated paraffin
    in whole mussel tissue were 9.2-9.9 days (10.1 µg/litre) and 13.1-19.8
    days (2.35 µg/litre) (Madeley et al., 1983a).

    4.3.3.2  Intermediate chain length chlorinated paraffins

         After 60-day exposures of mussels  (Mytilus edulis) to
    intermediate chain length paraffin with 52% Cl (CP-MH) at measured
    concentrations of 220 and 3800 µg/litre (which was above the limit
    of solubility in water), whole body BCFs were 429-2856 based on
    radioactivity measurements and 339-2182 based on parent compound
    analysis (Madeley & Thompson, 1983b).

    4.3.3.3  Long chain length chlorinated paraffins

         In mussels exposed to measured concentrations of 120-2180
    µg/litre of long chain length chlorinated paraffin with 43% Cl (CP-LL)
    and 460-1330 µg/litre of long chain length chlorinated paraffin with
    70% Cl for 60 days, whole body BCFs of 1158-261 (43% Cl) and 341-223
    (70% Cl), respectively, were observed when measured as radioactivity,
    and 87.2-1000 (43% Cl) and 105-167 (70% Cl) when based on parent
    compound analysis (Madeley & Thompson, 1983c,d).  However, the high
    doses exceeded the water solubility of the chlorinated paraffins.

    4.3.3.4  Comparative studies

         The accumulation during four weeks of two 14C-labelled
    chlorinated paraffins, polychloro[1-14C]hexadecane (C16;34% Cl,
    CP-ML) and 1-chloropolychloro[1-14C]dodecane (C12;69% Cl, CP-SH), was
    studied in the mussel  (Mytilus edulis) by Renberg et al. (1986). 
    Both compounds showed rapid uptake when added at concentrations of
    0.13 µg/litre (C16;34% Cl) and 0.0029 µg/litre or 0.13 µg/litre
    (C12;69% Cl) in water for 28 days.  Steady-state levels were reached
    within 14 days after exposure to 0.13 µg/litre.  The authors
    calculated the BCF values to be 6920 for C16;34% Cl and 138 000 for
    C12;69% Cl, based on fresh weight.  The mussels exposed to C12;69% Cl
    were studied for an additional 28 days without exposure.  The
    elimination rate for this chlorinated paraffin was slow, and 33% of
    the radioactivity remained in the tissues after 28 days.

    4.3.4  Aquatic plants

         The BCF after 10 days exposure to short chain chlorinated
    paraffin with 58% chlorination (CP-SH) has been estimated to be 3.5
    for the diatom  Sceletonema costatum (17.8 µg/litre) and 1.5 for the
    green alga  Selenastrum capricornutum (35 µg/litre) (Thompson &
    Madeley, 1983a,b).

    5.  ENVIRONMENTAL LEVELS AND HUMAN EXPOSURE

    5.1  Environmental levels

         Techniques for the analysis of chlorinated paraffin are described
    in section 2.3.2.  The major problem connected with the analysis of
    environmental samples is interference from other compounds.  In
    earlier studies, when pre-separation techniques were not as well
    developed, the concentrations may have been overestimated.  Another
    problem is that the chlorinated paraffin composition in the
    environment may be different from that of the original products,
    and the quantitative analysis has to be based on comparisons with
    the original products.  These difficulties make it clear that
    analytical results have to be regarded more as estimates than exact
    concentrations.

    5.1.1  Air

         No information on levels in the atmosphere has been found in the
    literature.

    5.1.2  Water and sediment

         Levels of chlorinated paraffins in water and sediment in the
    United Kingdom are summarized in Table 10.  Chlorinated paraffins have
    been detected in United Kingdom sea water at levels in the range of
    0.5-4.0 µg/litre for C10-20 and less than 2.0 µg/litre for C20-30
    (Campbell & McConnell, 1980).  The levels in sediments from the same
    areas were analysed; chlorinated paraffins were detected only in a few
    samples at levels up to 500 µg/kg wet weight for C10-20 and 600 µg/kg
    for C20-30.  The levels of chlorinated paraffins are low in water from
    rivers and reservoirs not receiving industrial/domestic effluents
    (C10-20, 1 µg/litre or below; C20-30, 2 µg/litre or below) and for
    waterways in industrialized regions (C10-20, up to 6.0 µg/litre; C20-30,
    0.5 µg/litre or below).  The level of C10-20 in the latter regions was
    higher than for C20-30.  Chlorinated paraffins were not detected in
    five drinking-water reservoirs either in the water (detection limit:
    0.5 µg/litre) or the sediment (detection limit: 250 µg/kg) (Campbell &
    McConnell, 1980).  The levels of C10-20 in sediment from non-marine
    water remote from industry were in the range up to 1000 µg/kg, except
    for a sewage sludge sample from the Liverpool area, which had levels
    of 4000-10 000 µg/kg.  C20-30 was detected only in one sample at
    50 µg/kg.  The levels of chlorinated paraffins in sediments close to
    industrial plants were found to be higher (C10-20 up to 15 000 µg/kg;
    C20-30 up to 3200 µg/kg wet weight).  The levels in sediment from these
    industrial areas were 1000 times higher than in the overlaying water
    columns, indicating the ability of chlorinated paraffins to adsorb on
    suspended solids.

        Table 10.  Levels of chlorinated paraffins in United Kingdom water (µg/litre) and sediment (µg/kg)
               (From: Campbell & McConnell, 1980)a

                                                                                                                                      

                                                       C10-20                                         C20-30
                                                                                                                                
                                         Range         Median     No. of samples        Range         Median      No. of samples
                                                       level      below detection                     level       below detection
                                                                  limit                                           limit
                                                                                                                                      

    Sea water
         water                           ND-4.0        0.5        7/15                  ND-2.0        ND          13/18
         sediment                        ND-500        ND         14/18                 ND-600        ND          15/18

    Fresh water remote from industry
         water                           ND-1.0        0.5        7/13                  ND-2.0        ND          7/11
         sediment                        ND-1000       ND         4/6                   ND-< 250      ND          4/5

    Fresh water close to industry
         water                           ND-6.0        1-2        4/25                  ND-0.5        ND          8/10
         sediment                        ND-15 000     1800       2/21                  ND-3200       50          3/9
                                                                                                                                      

    a    ND = not detected (detection limit in water = 0.5 µg/litre; in sediment = 50 µg/kg)
             Levels of chlorinated paraffins in water and sediment in Germany
    are summarized in Tables 11 and 12.  In 1987, chlorinated paraffins
    were detected at concentrations of about 1 µg/litre for C10-13 and
    20 µg/litre for C14-18 in the Danube, downstream of the confluence
    with the River Lech (BUA, 1992). The corresponding contents in the
    sediment were 300 and 1800 µg/kg dry weight, respectively.  In 1994,
    chlorinated paraffin concentrations in the Danube and River Lech were
    in the range of 0.05 to 0.12 µg/litre for C10-C13 and < 0.05 to
    0.19 µg/litre for C14-C17.  Also in 1994, the chlorinated paraffin
    concentrations (C10-C13) in sediment varied from 6-10 µg/kg dry
    weight in the lake of Constance to maximum concentrations of 76 µg/kg
    dry weight in the River Lech and 83 µg/kg dry weight in the Rhine
    (BUA, 1992).

        Table 11.  Concentrations (µg/litre) of short and intermediate chain length
               chlorinated paraffins in surface water in Germany (From: BUA, 1992)a

                                                                                                 

    Location                                      1987                        1994
                                           C10-13       C14-18         C10-13       C14-17
                                                                                                  

    River Lech at Augsburg                                             0.05         < 0.05

    River Lech at Gersthofen               0.50         4.5            0.08           0.09
    (upstream from a chlorinated
    paraffin production plant)

    River Lech at Langweid                 0.60         4.0            0.10           0.19
    (downstream from a chlorinated
    paraffin production plant)

    River Lech at Rain                                                 0.12           0.17

    River Danube at Marxheim               1.2          4.0            0.06         < 0.06
    (downstream from the mouth of
    the River Lech)

    River Danube at Marxheim (upstream     1.2          20             0.06           0.07
    from the mouth of the River Lech)
                                                                                                  

    a    The data from 1994 were produced with a more specific method than those from 1987.
         The two data sets are therefore difficult to compare.
    
        Table 12.  Concentrations (µg/kg dry weight) of short and intermediate chain length
               chlorinated paraffins in sediments from Germany (From: BUA, 1992)a

                                                                                                  

    Location                                      1987                        1994
                                           C10-13       C14-18         C10-13       C14-17
                                                                                                  

    Bodensee (middle)
      0-5 cm depth                                                     9-10         70
      5-12 cm depth                                                    6-9          < 10

    River Rhine (141 km) at Rheinfelden                                33-38        60

    River Rhine (152 km) at Rheinfelden,
      upper layer                                                      53-60        140
      lower layer                                                      26-32        85

    River Rhine, near German-Dutch
    border (2 sites)                                                   60-83        145-205

    River Main (3 sites)                                               24-55        160-260

    Outer Alster, Hamburg                                              35-36        370

    River Elbe at Hamburg (2 sites)                                    16-25        130-230

    River Lech, upstream from              400          2200           < 5-7        < 10
    chlorinated paraffin production
    plant

    River Lech, downstream from            700          1700           70-76        325
    chlorinated paraffin production
    plant

    Danube downstream from mouth           300          1800
    of the River Lech
                                                                                                  

    a    The data from 1994 were produced with a more specific method than those from 1987.
         The two data sets are therefore difficult to compare.
    
         Chlorinated paraffins were detected in water samples collected
    in the Bermuda Islands (Kraemer & Ballschmiter, 1987).  Water samples
    down to a depth of 1200 m were analysed, and the highest concentration,
    about 50 µg/litre, was found in the surface film. Chlorinated paraffins
    were not detected in water from the Maldives (detection limit:
    3 ng/litre).

         In surface sediment from Lake Zürich, 5 µg/kg of a chlorinated
    paraffin mixture with a carbon chain length of C14-18 and 52% chlorine
    (CP-MH) was measured (Schmid & Müller, 1985). In the same study it
    was reported that sewage sludge from a sewage treatment plant in an
    urban industrialized region with known contamination of heavy metals
    and organochlorine compounds contained chlorinated paraffins at a
    concentration of 30 000 µg/kg.

         In a field study performed by the US Environmental Protection
    Agency (Murray et al., 1988), samples from two watersheds were
    analysed by the method of Schmid & Müller (1985).  Both were close to
    a chlorinated paraffin manufacturing plant (Sugar Creek, Ohio) or
    industry using lubricating oils (Tinkers Creek, Ohio).  Chlorinated
    paraffins were detected in most samples from Sugar Creek in the low
    ppb range (< 8 µg/litre) near drainage and downstream from the plant. 
    Only a few samples upstream from the plant contained detectable
    levels of chlorinated paraffins (< 0.3 µg/litre) (detection limit:
    0.15 µg/litre).  Of the three chlorinated paraffin fractions studied, the
    fraction containing the long carbon chain length C20-30; 40-50% Cl
    (CP-LL) was generally present at highest concentration.  Sediments
    contained higher concentrations.  As much as 170 000 µg/kg dry weight
    of C20-30 was detected in sediment in an impoundment lagoon, whereas
    50 000 µg/kg of C14-17;50-60% Cl (CP-MH) and 40 000 µg/kg C10-12;
    50-60% Cl (CP-SH) were measured in the same sample.  In mussels
    (family  Unionidae) collected downstream from the plant, there were
    detectable levels of chlorinated paraffins (280 µg/kg C10-12, 170 µg/kg
    C14-17, 180 µg/kg C20-30).  The report concluded that the observed
    levels were most likely due to the manufacturing plant.  The samples
    collected in Tinkers Creek did not contain detectable amounts of
    chlorinated paraffins.  Most of the samples contained organic
    compounds, largely halogenated aromatics, at levels high enough to
    interfere and mask the presence of chlorinated paraffins.  Chlorinated
    paraffins were detected in samples collected from the process wastes
    stream inside the chlorinated paraffin plant.  The levels in these
    samples were: C10-12, 8.1 µg/kg; C14-17, 1.3 µg/kg; C20-30, 2.2 µg/kg.

         In 1979, 51 water samples and 51 bottom sediment samples were
    collected at 17 sites in Japan and analysed for the presence of
    chlorinated paraffins (C8-32).  Chlorinated paraffins were not
    detected in any of the water samples, while 24 bottom sediment samples
    from 11 sites contained chlorinated paraffins at concentrations of 600
    to 10 000 µg/kg (wet or dry weight not specified) (Environment Agency,
    Japan, 1981).  In 1980, 120 water samples and 120 bottom sediment

    samples were collected at 40 sites in Japan and were analysed for the
    presence of chlorinated paraffins (C8-32).  Chlorinated paraffins
    were not detected in any of the water samples but 31 bottom sediment
    samples from 13 sites contained chlorinated paraffins at concentrations
    of 500 to 8500 µg/kg.  However, the analytical methods were not
    specified and the detection limits were high (the detection limit was
    10 µg/litre for water and 500 µg/kg for bottom sediment) (Environment
    Agency, Japan, 1983).

    5.1.3  Soil

         No data on the occurrence of chlorinated paraffins in soil have
    been reported.

    5.1.4  Aquatic and terrestrial organisms

         The levels of chlorinated paraffins in organisms from various
    ecosystems in Sweden, determined using the method of Jansson et al.
    (1991), are shown in Table 13.  Chlorinated paraffins were found in
    all samples in the range of 130-4400 ng/g lipid (6.6-210 µg/kg tissue)
    (Jansson et al., 1993).  The terrestrial animals rabbit and moose had
    higher chlorinated paraffin concentration in their fat than any of the
    aquatic animals.  The chlorinated paraffin levels in fish-eaters were
    approximately the same as in the fish, compared to the dioxin and PCB
    levels, which were several times higher in fish-eaters.  The levels
    in seal and herring indicated no or only low biomagnification of
    chlorinated paraffins in their food chains.

         In a study by Campbell & McConnell (1980), chlorinated paraffins
    were detected in mussels, fish, seals and seabirds, as well as in
    seabird eggs, using the analytical method of Hollies et al. (1979)
    (Table 14).  The levels of C10-20 were higher than those of C20-30 in
    most organisms.  Mussels collected close to a chlorinated paraffin
    plant effluent discharge had levels of C10-20 up to 12 000 µg/kg.  The
    measured levels in the organisms were close to the levels in the
    sediment near the organisms, but 100 to 1000 times higher than those
    of water, thus indicating bioaccumulation.  The authors also detected
    trace amounts of chlorinated paraffins (C10-20) in the tissues of sheep
    grazing near a plant producing chlorinated paraffins.  The tissues
    containing the highest levels were liver (200 µg/kg), fat and kidney
    (50 µg/kg).  The fleeces of the sheep contained higher levels
    (350 µg/kg), and the authors suggest that this might have been due to
    aerial transport.  No chlorinated paraffin could be detected in sheep
    grazing far from plants producing chlorinated paraffins (detection
    limit = 50 µg/kg).

        Table 13.  The levels of chlorinated paraffins in various terrestrial and aquatic
               organisms in Swedena

                                                                                                 

    Organism                    Samplesc     Tissue      Extracted     CP (µg/kg     CP (µg/kg
                                                         lipid (%)     lipid)        tissue)d
                                                                                                 

    Rabbit                      15           muscle      1.1           2900          31.9
    Moose                       13           muscle      2.0           4400          88
    Reindeer                    31           fat         56            140           78
    Whitefish                   35           muscle      0.66          1000          6.6
    Arctic char                 15           muscle      5.3           570           30.2
    Herring (Bothnian Sea)      100          muscle      5.4           1400          75.6
    Herring (Baltic Proper)     60           muscle      4.4           1500          66
    Herring (Skagerrack)        100          muscle      3.2           1600          51.2
    Ringed sealb                7            blubber     88            130           114.4
    Grey seal                   8            blubber     74            280           207
    Osprey                      35           muscle      4.0           530           21.2
                                                                                                 

    a    Data from Jansson et al. (1993)
    b    The ringed seal was from Kongsfjorden, Svalbard, Sweden
    c    Pooled samples
    d    Calculated from the reported data
    
         In a study by Campbell & McConnell (1980), chlorinated paraffins
    were detected in mussels, fish, seals and seabirds, as well as in
    seabird eggs, using the analytical method of Hollies et al. (1979)
    (Table 14).  The levels of C10-20 were higher than those of C20-30 in
    most organisms.  Mussels collected close to a chlorinated paraffin
    plant effluent discharge had levels of C10-20 up to 12 000 µg/kg.  The
    measured levels in the organisms were close to the levels in the
    sediment near the organisms, but 100 to 1000 times higher than those
    of water, thus indicating bioaccumulation.  The authors also detected
    trace amounts of chlorinated paraffins (C10-20) in the tissues of sheep
    grazing near a plant producing chlorinated paraffins.  The tissues
    containing the highest levels were liver (200 µg/kg), fat and kidney
    (50 µg/kg).  The fleeces of the sheep contained higher levels
    (350 µg/kg), and the authors suggest that this might have been due to
    aerial transport.  No chlorinated paraffin could be detected in sheep
    grazing far from plants producing chlorinated paraffins (detection
    limit = 50 µg/kg).

        Table 14.  Chlorinated paraffins in organisms in the United Kingdom
               (Campbell & McConnell, 1980)

                                                                                              

    Species                    Tissuea   No. of                 Carbon chain-length and
                                         specimens              concentration in tissues
                                         analysedb              (means and ranges)c
                                                                                            
                                                      C10-20 (µg/kg)         C20-30 (µg/kg)
                                                      mean     range         mean     range

                                                                                              

    Aquatic organisms

    Plaice                     NS        6            30       ND-200        30       ND-200
    (Pleuronectes platessa)

    Pouting                    NS        4            100      ND-200        ND       ND
    (Trisopterus luscus)

    Mussel                     NS        9            3250     100-12 000    10       NDe-100
    (Mytilus edulis)

    Pike                       NS        2            25       ND-50         25       ND-50
    (Esox lucius)

    Grey seal                  Liver     4            75       40-100        ND       ND
    (Halichoerus grypus)       and
                               blubber
                                                                                              

    Table 14.  Cont'd

                                                                                              

    Species                    Tissuea   No. of                 Carbon chain-length and
                                         specimens              concentration in tissues
                                         analysedb              (means and ranges)c
                                                                                            
                                                      C10-20 (µg/kg)         C20-30 (µg/kg)
                                                      mean     range         mean     range
                                                                                              

    Birds

    Heron                      Liver     NR           NR       500-1200      NR       NDe
    (Ardea cinerea)            Liver     NR           NR       100-1000      NR       100-1500

    Guillemot                  Liver     NR           NR       100-1100      NR       NDe
    (Uria aalge)

    Herring gull               Liver     NR           NR       200-900       NR       100-500
    (Larus argentatus)

    Seabird eggsd                        23           220      ND-2000       20       ND-100
                                                                                              

    a    NS = Not specified
    b    NR = Not reported
    c    ND = Not detected (detection limit = 50 µg/kg, except where stated otherwise)
    d    9 species
    e    Detection limit = 100 µg/kg
             In 1980, 108 fish samples were collected at 28 places in Japan
    and were analysed for the presence of chlorinated paraffins. 
    Chlorinated paraffins were not detected in any of the samples.  The
    detection limit was 500 µg/kg (Environment Agency, Japan, 1983).

    5.1.5  Food and beverages

         Chlorinated paraffins, mostly C10-20, were detected in various
    food products in a limited study (Table 15) using the analytical
    method of Hollies et al. (1979).  C20-30 chlorinated paraffins were
    detected only in a few samples.  C10-20 chlorinated paraffins were
    found at levels up to 500 µg/kg in approximately 70% of the samples
    (Campbell & McConnell, 1980).

         Chlorinated paraffin residues have been detected in fish and
    sheep (see section 5.1.4).

    Table 15.  Chlorinated paraffins (C10-20) in human foodstuffs
               (Campbell & McConnell, 1980)

                                                                        

    Foodstuff class                    No. of foodstuff     Concentration
                                       samples tested          (µg/kg)
                                                                        

    Dairy products                           13                  300

    Vegetable oils and derivatives           6                   150

    Fruit and vegetables                     16                  25

    Beverages                                6                   NDa
                                                                        

    a    Not detected (detection limit = 50 µg/kg)

    5.2  General population exposure

         Chlorinated paraffins have been detected on human hands (Campbell
    & McConnell, 1980).  The hands of eight human volunteers were swabbed
    with toluene, and all had chlorinated paraffin levels of 0.8-4.0 µg
    C10-20 (per two hands).  C20-30 chlorinated paraffins (2 µg)
    were detected only on one person.  The authors suggested that the
    chlorinated paraffin content in foodstuffs, as well as direct transfer
    from manufactured articles via the hands, could contribute to human
    exposure.

         Owing to the high octanol-water partition coefficient, it is
    likely that the principle source of exposure of the general population
    to chlorinated paraffins is food.  However, due to lack of data,
    exposure to chlorinated paraffins via other routes cannot be ruled
    out.

    5.2.1  Concentrations in human tissues

         Chlorinated paraffins have been detected in postmortem tissue
    samples.  Campbell & McConnell (1980) measured the amount in 24 tissue
    samples and found up to 600 µg/kg of C10-20 in adipose tissue (median
    level: 100-190 µg/kg), up to 500 µg/kg in kidney (median level below
    90 µg/kg) and up to 1500 µg/kg in liver (median level below 90 µg/kg). 
    C20-30 chlorinated paraffins were detected only in a few samples and
    at a low level.  Schmid & Müller (1985) also detected chlorinated
    paraffins in adipose tissue at a concentration of 200 µg/kg.

    5.3  Occupational exposure

         Occupational exposure to chlorinated paraffins is likely among
    workers in production plants or in industries using chlorinated
    paraffins.  The US National Occupational Exposure Survey (1981-1983)
    indicated that 573 000 workers, including 38 000 women, were
    potentially exposed to chlorinated paraffins (NIOSH, 1990).  In
    Denmark, it was reported that 60 000 workers in 175 companies have
    been potentially exposed to chlorinated paraffins since 1964 (the
    amount produced and imported annually is 5000 tonnes) (Hansen et al.,
    1992).

         Campbell & McConnell (1980) detected chlorinated paraffins on
    human hands using the method of Hollies et al. (1979) (see section
    2.3.2).  When the hands of a worker in a chlorinated paraffin
    laboratory were swabbed with toluene, 800 µg of C10-20 and 400 µg
    of C20-30 were detected.

         Historical exposure data from machine shops, reported as
    reflecting worst-case situations, indicated exposures to chlorinated
    paraffins of 0.003-1.15 mg/m3 for operation such as milling, cutting
    and grinding (HSE, 1992).  Other exposure data suggested exposures to
    chlorinated paraffins ranging from 0.003 to 0.21 mg/m3.  However,
    it is not clear if these levels of exposure were intermittent or
    time-weighted averages.  There is no information on whether or not
    chlorinated paraffin aerosols are in the inhalable size range.

         Occupational exposure to short chain chlorinated paraffins has
    been estimated by the United Kingdom Health and Safety Executive by
    mathematical modelling using the "Estimation and Assessment of
    Substance Exposure" (EASE), developed as part of the guidance on new
    and existing substances by the Commission of the European Union (CEU)
    (HSE, 1992).  This model takes into account physico-chemical data such
    as vapour pressure and process details such as temperatures and the
    use of local exhaust ventilation.  It does not take into account the
    attenuating effect of decontamination of equipment or use of personal
    protective equipment.

         During the production of short chain chlorinated paraffins in
    closed systems, exposure is likely to be intermittent, and the model
    predicts that inhalation exposure to a substrate with a vapour
    pressure of less than 0.001 kPa is negligible (0 to 0.1 ppm). 
    Assuming a non-dispersive pattern of use and intermittent skin
    contact, the model predicts that exposures of the hand and forearm
    will be in the range of 0.1-1 mg/cm2 per day.  During formulation of
    short chain chlorinated paraffins (in closed systems) the model
    predicts negligible (0-0.1 ppm) inhalation exposure with formulation
    process temperatures of 40-50°C.  Skin exposure to the hands and
    forearms during formulation is predicted to be 0.1-1 mg/cm2 per day.

    Occupational exposure to short chain chlorinated paraffins during
    their use as metal-working fluids is extensive and the model predicts
    exposure of 0.1-1.5 mg/cm2 per day, assuming a chlorinated paraffin
    content in the fluid of 2-10%, or 5-15 mg/cm2 per day for speciality
    fluids which may contain more than 80% chlorinated paraffin.

    6.  KINETICS AND METABOLISM IN LABORATORY ANIMALS

         There is a lack of systematic investigation of the influence of
    carbon chain length and degree of chlorination in studies on the
    kinetics of chlorinated paraffins.  Studies have almost exclusively
    concerned short and intermediate chain length chlorinated paraffins.

    6.1  Absorption

    6.1.1  Oral exposure

         Chlorinated paraffins are absorbed after oral administration. 
    From the data presented in section 6.5 it appears that short chain
    length compounds are more readily absorbed than longer chain length
    compounds.  Absorption decreases with increasing carbon chain length
    and degree of chlorination.

    6.1.2  Dermal exposure

         Chlorinated paraffins are slowly absorbed by the dermal route
    in Sprague-Dawley rats (Yang et al., 1987).  Two 14C-labelled
    chlorinated paraffins, C18;50-53% Cl (CP-LH) and C28;47% Cl (CP-LL),
    were applied to rat skin (5-7 animals of each sex) at a concentration
    of 66 mg/cm2, approximately equivalent to 2000 mg/kg body weight. 
    Only 0.7% (males) and 0.6% (females) of the C18 dose was absorbed
    after 96 h.  Only 0.02% of the C28 dose was absorbed in males whereas
    in females the level was not detectable.  This indicates that
    increasing chain length leads to decreased permeability.  Of the
    absorbed C18 dose, 40% was exhaled as 14C-labelled CO2, and 20% was
    excreted in urine and 20% in faeces.

         The absorption of two chlorinated paraffins through human skin
    has been studied  in vitro (Scott, 1989).  There was no absorption of
    Cereclor S52 (C14-19;52% Cl, CP-MH) following a 54-h application to
    the surface of the epidermal membranes using five different receptor
    media.  Similarly, using Cereclor 56L (C10-13; 56% Cl, CP-SH; 18.5% w/w
    solution in a typical cutting oil) no absorption was detected for 7 h,
    but after 23 h a slow but steady rate of absorption was detected
    (e.g., 0.05 ± 0.01 µg/cm2 per h ± SEM; n = 6; receptor medium PEG-20
    oleyl ether in saline), which was maintained for the duration of the
    experiment (56 h).  Owing to the anticipated low rate of absorption,
    the chlorinated paraffin samples were spiked with [14C] n-pentadecane
    and [14C] n-undecane for Cereclor S52 and 56L, respectively, in
    order to facilitate detection of the absorbed material. Measurement of
    the 14C-alkanes was taken as a surrogate for the chlorinated
    paraffins, on the assumption that their rates of absorption were
    similar.

    6.1.3  Inhalation exposure

         No data on retention of chlorinated paraffins by inhalation have
    been reported.

    6.2  Distribution

    6.2.1  Short chain length chlorinated paraffins

    6.2.1.1  Mouse

         Female C57Bl mice were administered 12.5 MBq/kg body weight
    (340 µCi) (for autoradiography) or 1.25 MBq/kg body weight (34 µCi)
    (for determination of radioactivity) of 14C-labelled chlorododecanes
    (C12) with different chlorine contents (17.5% [CP-SL], 55.9% [CP-SH]
    and 68.5% [CP-SH]) either by gavage or intravenous injection (Darnerud
    et al., 1982). Uptake of radioactivity was found by autoradiography to
    be highest in tissues with high cell turnover/high metabolic activity,
    e.g., intestinal mucosa, bone marrow, salivary glands, thymus and
    liver.  The highest radioactivity was achieved with the chlorinated
    paraffin that had the lowest chlorine content.  It was found that the
    long period of retention of heptane-soluble radioactivity, which
    indicated unmetabolized substance, in liver and fat after oral dosing
    increased with degree of chlorination.  In this study it was also
    found that 30 to 60 days after injection of C12;17.5% Cl and
    C12;55.9% Cl a considerable retention of radioactivity was seen in
    the central nervous system.  Exposure of late gestation mice showed a
    transplacental passage of radioactivity, and 14C-labelling was
    primarily noted in the liver, brown fat and intestine of the fetuses.

    6.2.1.2  Rat

         Radioactivity was found in the liver, kidneys, adipose tissue and
    ovaries of Fischer-344 rats following administration of an unspecified
    single dose by gavage of 14C-labelled chlorinated paraffin (C10-13;58%
    chlorination, CP-SH) at the end of a 90-day dosing by gavage with the
    same chlorinated paraffin (IRDC, 1984c).

    6.2.2  Intermediate chain length chlorinated paraffins

    6.2.2.1  Rat

         Radioactivity was found initially in the liver and kidneys and
    later in adipose tissue and the ovaries of Fischer-344 rats following
    a single dose by gavage of 14C-labelled C14-17;52% Cl (CP-MH) at the
    end of a 90-day dosing in the diet with the same chlorinated paraffin
    (IRDC, 1984b).

         In male Wistar rats fed with a diet containing 0.4 or 40 mg/kg
    [36Cl]Cereclor S52 (C14-17;52% Cl, CP-MH) for 8 (40 mg/kg) or 10 weeks
    (0.4 mg/kg), equilibrium levels of radioactivity were established in

    liver and abdominal fat within 1 and 7 weeks, respectively (Birtley et
    al., 1980).  The equilibrium concentrations were 7000 µg/kg in liver
    and 30 000-40 000 µg/kg in fat after high exposure.  No radioactivity
    was detected in the brain or adrenal glands.

    6.2.2.2  Mouse

         The distribution of orally administered 14C-labelled
    polychlorohexadecane (C16;69% Cl, CP-MH) in female C57Bl mice was
    examined by whole body autoradiography (Biessmann et al., 1983).
    A high level of radioactivity was observed in the liver, brown
    fat, intestine, gall bladder, adrenal cortex and kidney of mice
    administered approximately 15 µmol/kg.  A high uptake of radioactivity
    was also observed in corpora lutea on days 1-4, and was still present
    30 days after administration.  A high level of radioactivity was also
    observed in the adrenal cortex at shorter post-injection times, and in
    brown and white fat and in the liver, which were still labelled after
    30 days.

         14C-Labelled [1-14C]polychlorohexadecane (C16;34.1% Cl, CP-ML)
    was given to C57Bl mice either by gavage (females) or intravenously
    (both sexes) at a radioactivity level of 370 kBq/animal (10 µCi)
    (corresponding to 0.44 µmol of the chlorinated paraffin) (Darnerud &
    Brandt, 1982).  No difference in the distribution patterns was found
    between the oral and intravenous administration routes.  After
    analysis by autoradiography a high level of radioactivity was found in
    tissues with a high cell turnover rate and/or high metabolic activity,
    and lower levels could be seen in the white fat depots.  High levels
    of radioactivity were observed in the liver, kidneys, spleen, bone
    marrow, brown fat, intestinal mucosa, pancreas, salivary gland and the
    Harderian gland 24 h after intravenous injection.  After 12 days high
    levels of radioactivity were seen in the adrenal cortex, abdominal
    fat and in the bile.  Later after injection (30 days), prominent
    radiolabelling of the brain was found which was as high as in the
    liver.  The chlorinated paraffin was also administered intravenously
    to pregnant mice, and uptake of radioactivity in the fetuses was
    observed.  When the mice were administered on day 10 of pregnancy no
    tissue-specific localization was found, but after administration in
    late pregnancy (day 17) the distribution pattern after 6 h was similar
    to that of adult mice when examined 24 h after administration.

         The distribution of radioactivity in the brain and liver has been
    studied after gavage administration of 14C-labelled polychloro-
    hexadecane (C16;69% Cl, CP-MH) (1.48 MBq/kg body weight or 40 µCi,
    corresponding to 1.1 mg/kg body weight) to pre-weaning NMRI mice
    (Eriksson & Darnerud, 1985).  The chlorinated paraffin was
    administered by gavage at the age of 3, 10 and 20 days, and the
    animals were killed 24 h and 7 days later.  The radioactivity in the
    brain declined more rapidly in the 3-day-old mice compared to the
    10- and 20-day-old mice. In the 10-day-old mice approximately 0.02% of

    the total administered dose was detected in the brain 24 h after
    administration.  Approximately 80% of the radioactivity in the brain
    was still present after 7 days.  In the liver the radioactivity
    disappeared more rapidly both in younger and older animals.  The
    radioactivity in the brain was found primarily in the white matter
    of the cerebellum, in the space between the neocortex and the
    mesencephalon and thalamus, the corpus callosum, the pons and the
    outer part of medulla spinalis.  The radioactivity was higher in the
    parts of the brain which also stained for myelin, and the levels at
    7 days were almost the same as those at 24 h. After whole body
    autoradiography, high levels of radioactivity were found in the liver,
    intestinal contents, adipose tissue and adrenals.  A differential
    labelling of the liver was observed in the 3-day-old mice, where only
    certain parts of the liver lobules were labelled.

    6.2.2.3  Bird

         The distribution of 14C-labelled polychlorohexadecane (C16;69%
    Cl, CP-MH) in female Japanese quail  (Coturnix coturnix japonica) was
    examined by whole body autoradiography (Biessmann et al., 1983).  Four
    hours after a single dose by gavage of approximately 4.8 µmol/kg to
    quail, high levels of radioactivity were observed in the liver,
    intestine, gall bladder, egg yolk, kidney, ovary, blood, hypophysis
    and retina. Twelve days after administration, radioactivity was
    observed only in the uropygial gland, white fat, liver and egg yolk.

         A study of the distribution after oral administration by gavage
    of 0.74 MBq (20 µCi) (approximately 20 Ci/mol) of either 14C-labelled
    polychlorohexadecane (C16;34% Cl, CP-ML) or (1-14C)-labelled
    polychlorododecane (C12;56% Cl, CP-SH) in female Japanese quail
     (Coturnix coturnix japonica) was performed by Biessmann et al.
    (1982).  The distribution patterns for the two chlorinated paraffins
    were similar, and high levels of radioactivity were initially (up to
    1 day) found in the liver, intestinal mucosa, spleen, bone marrow,
    oviduct, gall bladder and kidney.  After 4 and 12 days, high
    radiolabelling was observed in fat, the yolk of the follicles and
    the contents of the uropygial glands.

         The uptake of Cereclor S52 (C14-17;52% Cl, CP-MH) in mallard ducks
     (Anas platyrynchos) or ring-necked pheasants  (Phasianus colchicus)
    was studied by Madeley & Birtley (1980).  After a single oral dose of
    Cereclor S52 (10 g/kg) in duck, the highest levels of chlorinated
    paraffins were detected in fat (67 mg/kg wet weight), gut (15 mg/kg)
    and heart (7 mg/kg).  The pheasants were exposed to 1000 mg/kg in the
    diet for 5 days.  Only low levels were found in the heart (3.1 mg/kg)
    and gut (1.4 mg/kg).  No visible fat was available in the pheasants
    due to immaturity.  The levels in other organs in both species were
    low.  The method of analysis was thin layer chromatography (Hollies
    et al., 1979).

    6.2.2.4  Fish

         The distribution of polychloro-[1-14C]hexadecane (C16;34% Cl,
    CP-ML) has been studied in carp  (Cyprinus carpio) and bleak
     (Alburnus alburnus) (Darnerud et al., 1983).  After a single
    intra-arterial injection of 60-80 µg in carp, about 6% of the dose was
    excreted as 14CO2 in 96 h.  Radioactivity was observed, in the
    intra-arterially injected carps or in bleak exposed to contaminated
    water (125 µg/litre) for 14 days, in the bile, intestine, kidney,
    liver, gills and, particularly in bleak, in the nasal cavity, lens and
    skin.

    6.2.3  Long chain length chlorinated paraffins

    6.2.3.1  Rat

         After oral administration of 14C-labelled C22-26;70% Cl (CP-LH)
    to Fischer-344 rats at the end of a 90-day exposure period, a small
    part of the dose was absorbed (Serrone et al., 1987).  The highest
    level of radioactivity was found in the liver.  Retention of
    radioactivity in adipose tissue, which was eliminated slowly, was also
    observed.  In an identical study, C20-30;43% Cl (CP-LL) gave the
    highest levels in the liver and ovary (Serrone et al., 1987).

    6.2.3.2  Fish

         Rainbow trout  (Oncorhynchus mykiss) were fed diets containing 47 or
    385 mg/kg (dry weight) of Cereclor 42 (C20-30;Cl 42%, CP-LL) containing
    a 14C-labelled pentacosane (C25) with 42% Cl for 35 days and
    a control diet for the following 49 days (Madeley & Birtley, 1980).
    The chlorinated paraffin accumulated in the fish during the exposure
    period, mostly in the liver and gut.  The radioactivity decreased
    during the elimination period, more rapidly in the gut and liver
    than in the flesh, but was still detectable at the end of the
    experiment.  When the chlorinated paraffin was determined by thin-layer
    chromatography a lower level was noted as compared to determination
    of 14C-labelled molecules, suggesting metabolism in the fish.  Up to
    70% of the assimilated 14C in tissues was not associated with
    chlorinated paraffin after feeding for 13 days.

    6.2.3.3  Mussel

         Mussels  (Mytilus edulis) were fed suspended yeast cells dosed
    with 524 mg/kg (dry weight) Cereclor 42 (C20-30;42% Cl, CP-LL)
    containing a 14C-labelled pentacosane (C25) with 42% chlorination for
    47 days, and were then fed with untreated yeast for a further 56 days
    (Madeley & Birtley, 1980).  The uptake reached a plateau level after
    26 days of exposure, and the tissue concentration was always below
    11 mg/kg.  The highest level of chlorinated paraffin was detected in

    the digestive glands.  The chlorinated paraffin was eliminated rapidly,
    and less than 10% remained at the end of the experiment.  There was no
    evidence of metabolism since the expelled radioactivity was in the
    form of the parent compound.

    6.2.4  Comparative studies

         The uptake of three 14C-labelled chlorinated paraffins, C16;23%
    Cl (CP-ML), C16;51% Cl (CP-MH) and C12;68% Cl (CP-SH), was studied in
    rainbow trout  (Oncorhynchus mykiss) by Darnerud et al. (1989). After
    exposure to 3.64 µmol (C16) or 1.74 µmol (C12) in water for 7
    days and to uncontaminated water for up to 21 days, radiolabelling was
    observed in the bile, eye lens, brain and fat for C16;23% Cl, in the
    bile, intestine, fat and liver for C16;51% Cl, and in fat, intestine,
    liver and bile for C12;68% Cl.  The three different chlorinated
    paraffins showed an initially high uptake in the olfactory organs and
    gills.  The retention of radioactivity in the olfactory organs and
    gills was relatively higher for C16;23% Cl than for the more highly
    chlorinated paraffins. The long-time retention of radioactivity in
    fat-rich tissues increased with the degree of chlorination of the
    chlorinated paraffin preparation.

         The short-term uptake and elimination of chlorinated paraffins in
    bleak  (Alburnus alburnus) were studied by Bengtsson et al. (1979). 
    Groups of bleak (15 in each) were exposed for 14 days to five
    different Witaclor mixtures (Table 16), which were added to natural
    Baltic Sea water (salinity 0.7%) giving a concentration of 125
    µg/litre of water.  Five fish were analysed to determine the chlorine
    content (Lunde & Steinnes, 1975) at the end of exposure, and the rest
    were analysed 1 and 7 days after treatment.  It was found that the
    uptake was more effective for those Witaclor mixtures with short
    carbon chain length and low degree of chlorination, i.e. Witaclor 149
    and 159.  The elimination rates were slow, and 75 to 90% was detected
    7 days after exposure.

         In an extended study, bleak were exposed to Witaclor 149
    (C10-13;49% Cl, CP-SL), Witaclor 171P (C10-13;71% Cl, CP-SH) and
    Witaclor 549 (C18-26;49% Cl, CP-LL) via contaminated food for 91 days. 
    This was followed by an elimination period of 316 days (Bengtsson &
    Baumann Ofstad, 1982).  The concentrations of chlorinated paraffins in
    the food were 590, 2500 and 5800 mg/kg of C10-13;49% Cl, 3180 mg/kg of
    C10-13;71% Cl and 3400 mg/kg of C18-26;49% Cl.  Three fish from
    each exposure group were analysed at different time-points during
    accumulation or elimination periods.  The most effective uptake was
    observed for C10-13;49% Cl, whereas the slowest uptake was detected for
    C18-26;49% Cl.  Efficiencies of uptake were 12% for C10-13;49% Cl, 6%
    for C10-13;71% Cl and 2% for C18-26;49% Cl.  The highest retention was
    observed for C10-13;71% Cl, which remained in the tissue at a
    steady-state level during the whole elimination period.  The uptake of
    C18-26;49% Cl was inefficient, and during the elimination period 50%

    was lost within 4 to 5 weeks.  The remaining amount appeared to be
    constant for the rest of the experiment.  The rate of elimination was
    slowest for the Witaclor mixture with the shortest carbon chain length
    and highest degree of chlorination.  After 625 days of depuration the
    fish still had detectable levels of C10-13;71% Cl, as determined by the
    analytical method of Gjos & Gustavsen (1982) (Renberg et al., 1986).

    Table 16.  Structures of the chlorinated paraffins used in a study on
               bleak (Alburnus alburnus) (From: Bengtsson et al., 1979)

                                                                          

    Tested         Carbon    Chlorine   Acronyma   Accumulation  Half-life
    formulation    chain     content               coefficientb  (days)b
                   length    (%)
                                                                          

    Witaclor 149   C10-C13   49         CP-SL           770           13

    Witaclor 159   C10-C13   59         CP-SH           740           34

    Witaclor 171P  C10-C13   71         CP-SH           140           7

    Witaclor 350   C14-C17   50         CP-MH           40            30

    Witaclor 549   C18-C26   49         CP-LL           10            7
                                                                          

    a    The classification is given in Table 1
    b    Calculated by Zitko (1980)

    6.3  Metabolic transformation

    6.3.1  Short chain length chlorinated paraffins

         Darnerud (1984) demonstrated that inducers and inhibitors of
    cytochrome P-450 (CYP) affect the rate of degradation of 14C-labelled
    polychlorinated dodecanes (C12) containing 68.5% (CP-SH), 55.9%
    (CP-SH) and 17.4% Cl (CP-SL) to 14CO2 in exposed C57Bl mice. 
    Pretreatment with the inhibitor piperonyl butoxide decreased the
    amount of 14CO2 formed, and the decrease was more pronounced with
    increasing degree of chlorination. The inhibitor metyrapone decreased
    the exhalation of 14CO2 but was only investigated in mice exposed
    to C12;68.5% Cl. The cytochrome P-450 (CYP2B1; CYP2B2) inducer,
    phenobarbital, moderately increased the rate of 14CO2 formation from
    chlorinated paraffin with 68% Cl, whereas the P-448 (CYP1A1; CYP1A2)
    inducer, 3-methylcholanthrene, did not affect the degradation rate,
    indicating a cytochrome P-450-dependent metabolism of chlorinated
    dodecanes yielding 14CO2.

    6.3.2  Intermediate chain length chlorinated paraffins

         Female Sprague-Dawley rats in groups of four were exposed
    intravenously to 5-6 mg/kg body weight of 14C-labelled poly-
    chlorinated hexadecane (C16;65% Cl, CP-MH) (Åhlman et al., 1986). 
    Less than 3% of the radioactivity in the bile was due to unchanged
    parent compound. The metabolites in the bile appeared to be conjugates
    of  N-acetylcysteine (mercapturic acid) and glutathione.

    6.4  Elimination and excretion

    6.4.1  Short chain length chlorinated paraffins

         The exhalation of 14CO2 was compared after single gavage or
    intravenous administration to female C57Bl mice of 1.25 MBq/kg body
    weight (34 µCi) of three chlorododecanes (C12) with different
    chlorine contents (17.5% [CP-SL], 55.9% [CP-SH] and 68.5% [CP-SH])
    (Darnerud et al., 1982).  Of the administered radioactive dose 52% of
    C12;17.5% Cl, 32% of C12;56% Cl and 8% of C12;68% Cl were exhaled as
    14CO2 within 12 h after dosing by either route.  The major excretion
    route for C12;56% Cl was by urine (intravenous: 21%; oral: 29%) and
    for C12;68% Cl was by faeces (intravenous: 8.6%; oral: 21%).  The
    total elimination decreased as the chlorine content increased.

    6.4.2  Intermediate chain length chlorinated paraffins

    6.4.2.1  Rat

         The half-time for removal of radioactivity from abdominal fat was
    estimated during and after dietary administration for 8 or 10 weeks of
    0.4 and 40 mg/kg feed of [36Cl]Cereclor S52 (C14-17;52% Cl, CP-MH) in
    male Wistar rats (Birtley et al., 1980).  Equilibrium in liver and
    abdominal fat was reached at 1 and 7 weeks, respectively.  The
    half-time for removal was about 8 weeks for abdominal fat, and it was
    observed that the level of radioactivity in the liver declined below
    the detection limit within one week.

         Female Sprague-Dawley rats in groups of four were exposed
    intravenously to 5-6 mg/kg body weight of 14C-labelled polychlorinated
    hexadecane (C16;65% Cl, CP-MH) (Åhlman et al., 1986).  Approximately
    10% of the administered dose was excreted in the bile after 24 h,
    whereas excretion in the urine and faeces was less than 0.5% after
    48 h.

    6.4.2.2  Mouse

         The elimination of radioactivity was studied in female C57Bl mice
    after gavage or intravenous administration of a uniformly 14C-labelled
    polychlorohexadecane (C16;69% Cl, CP-MH) (1.6 µmol/kg) (Biessmann
    et al., 1983).  After 8 h, only about 1% of the dose was exhaled 

    as 14CO2 for both administration routes.  Most of the
    radioactivity was excreted in faeces when administrated by gavage, and
    after 8 h 22% was recovered in faeces and 1.2% in urine.  After 96 h,
    66% was recovered in faeces and 2.9% in urine.  After intravenous
    administration, 2.1% was excreted in faeces and 1% in urine after 8 h,
    and 43% was excreted in faeces and 3% in urine after 96 h.

         The excretion of [1-14C]polychlorohexadecane (C16;34.1% Cl,
    CP-ML) (59 kBq/animal, or 1.5 µCi) after intravenous or gavage
    administration to C57Bl mice was studied by Darnerud & Brandt (1982). 
    Twelve hours after intravenous injection, 12% of the radioactive dose
    was recovered in urine, 44% in expired air (as 14CO2) and 4%
    in faeces. Twelve hours after gavage administration, 6% of the
    radioactive dose was recovered in urine, 33% in the expired air and
    14% in faeces.

    6.4.2.3  Bird

         The elimination of radioactivity was studied in female Japanese
    quail  (Coturnix coturnix japonica) after gavage or intravenous
    administration of a uniformly 14C-labelled polychlorohexadecane
    (C16;69% Cl, CP-MH) (0.48 µmol/kg) (Biessmann et al., 1983).  Of the
    administered dose, 1.6% was exhaled as 14CO2 after gavage
    administration and 0.9% after intravenous administration.  Of the
    administered dose 16% was excreted in faeces/urine after 8 h and 58%
    after 96 h.

    6.4.3  Long chain length chlorinated paraffins

         A 14C-labelled chlorinated paraffin, C18; 50-53% Cl (CP-LH), was
    administered by gavage as a single dose of 500 mg/kg to three female
    Sprague-Dawley rats (Yang et al., 1987).  After 24 h, 1% of the
    radioactive dose was recovered in the urine, 1.5% in the expired air
    and 22% in the faeces.  After 96 h, 1.9% of the radioactive dose was
    recovered in the urine, 3.3% in the expired air, 5% in body tissue and
    76% in the faeces.

    6.4.4  Comparative studies

         In a study by Beissmann et al. (1982), 148 kBq (4 µCi)
    (approximately 20 Ci/mol) of either 14C-labelled polychlorohexadecane
    (C16;34% Cl, CP-ML) or 14C-labelled polychlorododecane (C12;56% Cl,
    CP-SH) was administered by gavage to Japanese quail  (Coturnix
     coturnix japonica).  A considerably higher level of radioactivity
    was found in the gall bladder and kidney after C12 administration
    compared with C16.  On the other hand, the radioactivity in the yolk
    of the first ten eggs was higher after C16 gavage than after C12
    gavage.  After 8 h, 39% of the C16 dose and 22% of the C12 dose was
    exhaled as 14CO2, indicating that the rate of metabolism is
    influenced by the chain length and/or the degree of chlorination.

    7.  EFFECTS ON LABORATORY MAMMALS AND  IN VITRO TEST SYSTEMS

    7.1  Acute exposure

    7.1.1  Lethal doses

         The acute oral toxicity of chlorinated paraffins has been studied
    in rats and mice (Table 17).  In all studies, the LD50 was reported
    to be greater than the highest administered dose (i.e. always
    > 4 g/kg body weight).  After inhalation of Chlorowax 500C (C12;59% Cl,
    CP-SH), an LC50 was not established in the one reported study (LC50
    > 3300 mg/m3).  The LD50 for dermal exposure of rabbits to
    Chlorowax 500C (C12;59% Cl, CP-SH) was in excess of approximately
    13 g/kg body weight (Howard et al., 1975).

        Table 17.  Acute toxicity of chlorinated paraffins

                                                                                                   

    Chlorinated       Compounda       Species       Test           Exposure         Reference
    paraffin                                                       concentration
                                                                                                   

    C12;60% Cl        (CP-SH)         rat           oral LD50      > 13.6 g/kg      Bucher et
                                                                                    al. (1987)

    C12;59% Cl        Chlorowax       rat           oral LD50      > 21.5 g/kg      Howard et
                      500C (CP-SH)                                                  al. (1975)

    C12;59% Cl        Chlorowax       rabbit        dermal         > 13 g/kg        Howard et
                      500C (CP-SH)                  LD50                            al. (1974)

    C12;59% Cl        Chlorowax       rat           inhalation     > 3300           Howard et
                      500C (CP-SH)                  LC50           mg/m3            al. (1975)

    C12;60% Cl        (CP-SH)         mouse         oral LD50      > 27.2 g/kg      Bucher et
                                                                                    al. (1987)

    C10-13;41-70% Cl                  rat           oral LD50      > 4 g/kg         Birtley et
                                                                                    al. (1980)

    C14-17;51-60% Cl                  rat           oral LD50      > 4 g/kg         Birtley et
                                                                                    al. (1980)

    C24;40% Cl        Chlorowax 40    rat           oral LD50      > 17.7 g/kg      Howard et
                      (CP-LL)                                                       al. (1975)

    C23;43% Cl        (CP-LL)         rat           oral LD50      > 13.6 g/kg      Bucher et
                                                                                    al. (1987)
                                                                                                   

    Table 17.  (Cont'd)

                                                                                                   

    Chlorinated       Compounda       Species       Test           Exposure         Reference
    paraffin                                                       concentration
                                                                                                   

    C23;43% Cl        (CP-LL)         mouse         oral LD50      > 27.2 g/kg      Bucher et
                                                                                    al. (1987)

    C20-30;41-70% Cl                  rat           oral LD50      > 4 g/kg         Birtley et
                                                                                    al. (1980)

    C24;70% Cl        Chlorowax 70    rat           oral LD50      > 50 g/kg        Howard et
                      (CP-LH)                                                       al. (1975)

    C24;70% Cl        Chlorez 700     rat           oral LD50      > 50 g/kg        Howard et
                      (CP-LH)                                                       al. (1975)

    C24;70% Cl        Chlorowax 70    guinea-pig    oral LD50      > 25 g/kg        Howard et
                      (CP-LH)                                                       al. (1975)

    C24;70% Cl        Chlorez 700     guinea-pig    oral LD50      > 25 g/kg        Howard et
                      (CP-LH)                                                       al. (1975)
                                                                                                   

    a    The classification is given in Table 1
    
    7.1.2  Non-lethal doses

    7.1.2.1  Oral route

         In a single-administration experiment, F-344/N rats and B6C3F1
    mice were dosed by gavage up to 13.6 g/kg body weight (rats) and
    27.2 g/kg body weight (mice) of C12;60% Cl (CP-SH) or C23;43% Cl
    (CP-LL) dissolved in corn oil. No deaths or compound-related toxic
    effects were noted during the 14-day observation period.  However, the
    animals were inactive with diarrhoea for 2-6 days after dosing, which
    was attributed to the large volumes of material administered (NTP,
    1986a,b; Bucher et al., 1987).

         Female or male Wistar rats were administered by gavage a single
    oral dose of different chlorinated paraffins (C10-13; 41-51%, 51-61% or
    61-70% Cl), with a range of maximum doses of 4-13 g/kg body weight,
    and were observed for 7 days (ICI, 1965, 1966, 1968, 1969, 1971, 1973,
    1974a,b; Birtley et al., 1980).  Clinical signs of toxicity, such as
    piloerection, muscular incoordination and faecal and urinary
    incontinence, were observed in rats that received doses of 2 g/kg body

    weight or more (generally independent of the chlorine content). 
    Recovery was usually complete by day 7.  There were no deaths except
    for one rat treated with 13 g/kg body weight of C10-13;63% Cl.

         Similar findings were reported for C14-17;51-60% Cl and
    C20-30;41-51%, 51-61% or 61-70% Cl (Birtley et al., 1980).  The
    toxicity of these chlorinated paraffins was reported to be lower than
    that of the short chain length chlorinated paraffins.

    7.1.2.2  Inhalation route

         No toxic response was observed in rats exposed to a concentration of
    3300 mg/m3 of Chlorowax 500C (C12;59% Cl, CP-SH) for one hour (Howard
    et al., 1975)

    7.1.2.3  Intraperitoneal route

         Three different chlorinated paraffin preparations, Chlorez 700
    (C20;70% Cl, CP-LH), Paroil 170-HV (C11;70% Cl, CP-SH) and
    Chloroparaffin 40 (chain-length not given, 40% Cl), were administered
    intraperitoneally as single doses (Chlorez and Chloroparaffin
    100 mg/kg body weight; Paroil 52 mg/kg body weight) to male Wistar rats
    (Ahotupa et al., 1982).  The activities of various drug-metabolizing
    enzymes from liver, kidney and small intestinal mucosa were determined
    after 24 h, 7 days or 21 days.  Minor but significant changes in the
    intestinal activities of aryl hydrocarbon hydroxylase (increase),
    UDP-glucuronosyltransferase (decrease) and epoxide hydrolase
    (increase) were induced by Paroil 170-HV, and in the kidney activity
    of aryl hydrocarbon hydroxylase by Chlorez 700, when compared to
    polychlorinated biphenyls and naphthalenes.

    7.1.3  Skin and eye irritation

    7.1.3.1  Short chain length chlorinated paraffins

         In a study by Hoechst (1986b), 0.5 ml of undiluted C10-13;50%
    Cl(CP-SH) was applied under a semi-occlusive dressing to the shaven
    skin of three rabbits for 4 h.  The skin was examined for signs of
    irritation for up to 72 h after the chlorinated paraffin had been
    removed, but none were seen during the test.

         When 0.5 ml of C10-13;70% Cl(CP-SH) was applied under a
    semi-occlusive dressing to the shaven skin of three rabbits for 4 h,
    one rabbit showed clearly defined erythema (grade 2 on a 0-4 scale) at
    48 and 72 h.  The other two animals showed "slightly noticeable"
    erythema (grade 1).  Very slight oedema (grade 1) was noted in two
    animals for up to 24 h.  By day 7, all signs of irritation were
    completely resolved (Hoechst, 1983).

         Two studies investigated C10-13;70% Cl(CP-SH).  In one study the
    chlorinated paraffin contained 1 or 2% of an epoxidised vegetable oil
    stabilizer with and without additives (0.1% oxalic acid or 0.05%
    benzotriazole) (ICI, 1965).  Very mild to mild desquamation was only
    noted following the applications of chlorinated paraffins containing
    additives.  The reactions were described as occasional, transient and
    inconsistent.  It was not stated how many applications were made
    before these reactions were seen.  In another study, no signs of
    irritation were noted following repeated application of a chlorinated
    paraffin containing 0.1 or 2% benzoyl peroxide initiator (ICI, 1974a).

         Two studies investigated the effects of three C10-13;63%
    chlorinated paraffins (CP-SH), containing up to 3% epoxy soya oil
    stabilizers or other unspecified additives (ICI, 1973, 1974a).  For
    all three paraffins, erythema was usually noted following two to four
    applications, although on one occasion erythema was noted in 1/3
    animals after only one application.  The severity of the reactions was
    not described.  Desquamation was also noted following three or four
    applications and increased in severity with further treatments.  In
    one study (with 0.7% epoxy carboxylate stabilizer) the desquamation
    was described as severe following the fourth application when the
    study was terminated (ICI, 1973).

         Studies have been conducted using C10-13 chlorinated paraffins
    which were 48(CP-SL), 50, 52 or 55% chlorinated (CP-SH) (ICI,
    1967, 1968, 1969, 1971, 1974a,b).  In most of these studies the
    chloroparaffins contained 0.2 or 2% epoxy stabilisers.  In one study
    with 48 or 55% chlorinated paraffins, containing 0.2% epoxy octyl
    stearate stabilizer, no signs of irritation were noted (ICI, 1969). 
    In the other studies there was mild or slight erythema, and mild
    desquamation was usually noted following the second or third
    application.  In one study, testing C10-13;52% with 2% epoxidised octyl
    oleate stabilizer, erythema was noted following the first application
    (ICI, 1968).  It was observed in 4/5 of the studies that the reactions
    did not worsen following further applications, although in one study
    (testing a 52% chlorinated paraffin with unspecified additives),
    slight erythema, noted after the second application, worsened to
    severe erythema with slight necrosis after the third application, when
    the study was terminated (ICI, 1971).

         An unspecified volume of C10-13;40% Cl(CP-SL), containing 1% epoxy
    soya oil stabilizer, produced slight desquamation following the second
    application and mild erythema after the third (ICI, 1966).  This
    condition persisted throughout the remaining applications until the
    end of the study when small scattered ulcers developed.

         Two studies in rats were conducted to investigate the potential
    for skin irritation of two short chain length chlorinated paraffins
    (C10-11) which were 49% (CP-SL) and 60% chlorinated (CP-SH) (ICI, 1980,
    1982c).  Repeated and single application tests were conducted. No

    signs of irritation were noted following a single application of the
    more chlorinated paraffin, although slight desquamation was noted in
    2/6 rats, 3-6 h after the treatment with the less chlorinated
    paraffin.  Both chlorinated paraffins produced slight erythema and/or
    slight desquamation with repeated applications.

         Rats were treated with 0.1 ml of C14-17;51-60% Cl(CP-MH), or
    C20-30;41-51%(CP-LL), 51-61%(CP-LH) or 61-70% Cl(CP-SH), for up to
    six 24-h periods.  The treatment periods were separated by 24-h
    treatment-free periods. In some of the studies the chlorinated
    paraffins contained epoxy stabilizers.  Mild irritation was seen with
    C14-17 chlorinated paraffins, but it is not clear if the response was
    due to the stabilizer.  No signs of irritation were seen with C20-30
    (Birtley et al., 1980).

         A C10-13;61% chlorinated paraffin (Cereclor 60HS) and a 50%
    chlorinated paraffin (Cereclor 50 HS) of unidentified carbon chain
    length produced mild or moderate skin irritation following a single
    occlusive application to intact or abraded skin of rabbits.  It was
    stated that varying degrees of erythema persisted for 72 h (ICI
    1975a,b).

         In other studies (BUA, 1992) different short and long chain
    length chlorinated paraffins were applied to the skin and eyes of
    rabbits (skin: C10-13;58% Cl, C19;44% Cl, C20-30;70% Cl; eyes: C12;59%
    Cl, C20-30;70% Cl). Only a weak or no irritating effect was observed,
    which decreased with increasing chain length.

         The eye irritation potential of three different chlorinated
    paraffins, C10-13;65% Cl(CP-SH), which contained either 2.5 or 2% of
    two different additives or 0.7% of an epoxy stabilizer, was tested in
    two studies (ICI, 1971, 1974a).  Either 0.1 ml or "one drop" of the
    chloroparaffin was instilled into one conjunctival sac of groups
    of three rabbits.  Similar results were reported for all three
    formulations: practically no initial pain (2 on a 6-point scale) was
    noted.  Slight irritation (3 on a 8-point scale), shown by redness
    and chemosis (only noted in the formulation containing the epoxy
    stabilizer) of the conjunctiva with some discharge, lasted for 24 h. 
    One drop of 52% or 40% chlorinated paraffins, containing unspecified
    additives or 1% epoxy stabilizer, was also tested (ICI, 1966, 1971). 
    With the 52% chlorinated paraffin, slight immediate irritation was
    followed by slight redness of the conjunctiva which lasted for 24 h. 
    With the 40% chlorinated paraffin, mild congestion was noted at 1 h
    but no effects were seen at 24 h.

    7.1.3.2  Intermediate and long chain length chlorinated paraffins

         Intermediate and long chain chlorinated paraffins were tested
    in eye irritation studies with a single application of 0.1 ml of
    C14-17;51-60% Cl(CP-MH), C20-30;41-50%(CP-LL), 51-60% or 61-70%
    Cl(CP-LH).  No signs of eye irritation were seen (Birtley et al.,
    1980).

    7.1.4  Skin sensitization

         The maximization method was used to assess the skin sensitization
    potential of a chlorinated paraffin (C10-13;56% Cl, CP-SH) with 1%
    epoxide stabilizer (Edenol D81) and 1% tris-nonylphenyl phosphite
    (TNPP) (Hoechst, 1983b).  When challenged with undiluted chlorinated
    paraffin, 1/20 test animals showed hardly perceptible erythema 24 h
    after challenge, and 1/20 test and 1/10 control animals showed clearly
    defined erythema or slight oedema at 72 h.  The chlorinated paraffin
    tested did not induce skin sensitization in this study.

         The same chlorinated paraffin (C10-13;56% Cl, CP-SH), with 1% of a
    different epoxide stabilizer (Rutapox CY 160) and 1% TNPP, was tested
    using the same method (Hoechst, 1984).  When challenged with undiluted
    chlorinated paraffin, 5/20 test animals showed clearly defined erythema
    and another two showed hardly perceptible erythema.  None of the
    control animals showed any evidence of a skin reaction.  A second
    challenge was performed 2 weeks after the first.  On this occasion
    4/20 test animals showed clearly defined erythema and another four
    showed hardly perceptible erythema or slight oedema.  The authors
    concluded that the substance tested was a sensitizer.  However, as
    less than 30% of the test group showed a clear reaction and it is
    possible that the epoxide stabilizer was responsible for producing the
    sensitization reactions, this study is not considered to provide
    conclusive evidence that C10-13;56% Cl is a skin sensitizer.

         An undiluted chlorinated paraffin (C10-13;52% Cl, CP-SH) was
    applied to the ears of six guinea-pigs on three successive days (ICI,
    1971).  Slight erythema was noted when, 4 days later, undiluted
    chloroparaffin was applied to the animals' flanks, but it was not
    stated how many animals showed a reaction.  Four control animals also
    showed slight erythema at challenge.  It does not appear that this
    chlorinated paraffin elicited a sensitization response in this study.

    7.2  Repeated exposure

         Studies involving repeated exposure have demonstrated that the
    liver, kidneys and thyroid are the target organs for the toxicity of
    chlorinated paraffins.

    7.2.1  Oral route

    7.2.1.1  Short chain length chlorinated paraffins

    a)  Rat, 14-day studies

         In a range-finding study, a short chain chlorinated paraffin
    (C10-13;58% Cl) (CP-SH) was administered to Fischer-344 rats in
    the diet for 14 days at concentrations of 0, 900, 2700, 9100 and
    27 300  mg/kg feed, equivalent to approximately to 0, 100, 300, 1000
    and 3000 mg/kg body weight per day (IRDC, 1983c).  There were five male
    and five female rats per group. No deaths occurred during the study.  A
    marked reduction in body weight and food consumption was seen in the
    highest dose group, which was attributed to reduced palatability of
    the diet caused by the chlorinated paraffin.  The relative liver
    weight was increased (20-240%) in all dose groups compared to
    controls.  The activity of liver aminopyrine demethylase (APDM) was
    increased in females, and cytochrome P-450 values increased in both
    sexes in all dosed groups.  Liver enlargement was observed in some
    rats in the groups fed 2700 to 27 300 mg/kg, and a dose-related
    increase in the incidence of hepatocellular hypertrophy was present in
    all treated groups.  Myocardial atrophy was observed at the two
    highest dose levels although the relationship to treatment was
    unclear.  The lowest-observed-effect level (LOEL) in this study was
    100 mg/kg body weight per day.

         A short chain length chlorinated paraffin with 58% Cl (CP-SH) was
    administered by gavage in corn oil to Fischer-344 rats (five/dose of
    each sex) for 14 days at dose levels of 0, 30, 100, 300, 1000 and
    3000 mg/kg body weight per day (IRDC, 1981a).  A significant decrease
    in body weight gain in females in the high dose group was noted.  A
    dose-related increase in APDM activity was observed in females fed
    300-3000 mg/kg, whereas in males there was an increase only in the
    group treated with 1000 mg/kg.  Cytochrome P-450 levels were
    significantly increased in females treated with 1000 mg/kg, and
    microsomal protein concentration increased in females dosed with
    3000 mg/kg.  Liver enlargement occurred in both sexes in the 300, 1000
    and 3000 mg/kg groups, and mild hepatocellular hypertrophy in all
    animals of the 1000 and 3000 mg/kg groups.  The absolute and relative
    liver weight was increased (20-150%) at doses of 100 mg/kg or more. 
    Statistically significant reduction of thymus and ovary weight was
    observed at 3000 mg/kg.  The no-observed-effect level (NOEL) in this
    study was considered to be 30 mg/kg body weight per day and the LOEL
    100 mg/kg body weight per day, based on liver weight increases.

         In a 16-day study on F-344/N rats (groups of five), the animals
    were administered a short chain length chlorinated paraffin (C12;60%
    chlorination) (CP-SH) by gavage in corn oil daily (5 days per week) at
    doses of 0, 469, 938, 1875, 3750 and 7500 mg/kg body weight per day
    for 16 days (NTP, 1986a; Bucher et al., 1987).  At the highest dose

    level there was reduced body weight gain (22% in males and 16% in
    females), and 1/5 male rats and 2/5 females died before the end of the
    study.  Enlarged livers were observed in every dose group except the
    females fed 469 mg/kg.  No histopathology was performed.  The LOEL in
    this study was considered to be 469 mg/kg body weight per day.

    b)  Rat, 90-day studies

         Fischer-344 rats (groups of 10 males and 10 females) were given a
    short chain chlorinated paraffin (C12;60% chlorination) (CP-SH) in
    corn oil by gavage on 5 days a week for 13 weeks at doses of 0, 313,
    625, 1250, 2500 and 5000 mg/kg body weight per day (NTP, 1986a; Bucher
    et al., 1987).  Body weight gain was reduced by approximately 10% in
    males at the two highest dose levels.  A dose-related statistically
    significant increase in relative liver weight (17-100% for males;
    30-100% for females) was observed in all treated rats.  Hepatocellular
    hypertrophy was noted in all rats in the highest dose group, and
    nephrosis was more frequent in this group (10/10 males; 3/10 females)
    compared to controls (8/10 males; 0/10 females).  Rats in other dose
    groups were not examined microscopically.  On the basis of an increase
    in liver weight, the LOEL in this study was 313 mg/kg body weight per
    day.

         In a 13-week study Fischer-344 rats were administered a short
    chain length chlorinated paraffin (C10-13;58% Cl, CP-SH) in corn oil by
    gavage at doses of 0, 10, 100 and 625 mg/kg body weight per day in
    groups of 15 animals of each sex (IRDC, 1984a).  In the groups treated
    with 100 mg/kg or more, increased weights of the liver (30-110%) and
    the kidneys (20-100%) were observed.  At the highest dose level
    thyroid weights were increased.  Hepatocellular hypertrophy was
    observed at 100 and 625 mg/kg.  In these groups hypertrophy and
    hyperplasia of the thyroid were also observed.  There was trace-to-mild
    chronic nephrosis in the kidney of males treated with 625 mg/kg, and in
    females in the high-dose group, in which pigmentation of the renal
    tubular epithelia also occurred.  The NOEL was considered to be 10 mg/kg
    body weight per day on the basis that no treatment-related microscopic
    changes were found in any tissue at this dose.  The LOEL was 100 mg/kg
    body weight per day based on increased liver and kidney weights and
    hypertrophy in liver and thyroid.  When the same doses were
    administered in the diet essentially identical results were obtained
    (IRDC, 1984c).

         Male and female Fischer-344 rats (5 or 10 per group) were
    administered Chlorowax 500C (C12;58% Cl, CP-SH) in corn oil by gavage
    at doses of 0, 313 and 625 mg/kg body weight per day for up to 90 days
    (Elcombe et al., 1994).  The relative liver weight was increased at
    both doses (50 and 75%).  Hepatic peroxisomal ß-oxidation (palmitoyl
    CoA oxidation) was statistically significantly increased in a
    dose-related manner from day 15.  The activity of thyroxine-UDPG-
    glucuronosyltransferase was significantly increased (at least 150%) at

    both dose levels from day 15 onwards.  Thyroid follicular cell
    hypertrophy was observed at all time points, and hyperplasia at days
    56 and 91.  Replicative DNA synthesis was increased in thyroid
    follicular cells at day 91.  Renal tubular eosinophilia was observed
    in males from day 15.  In renal tubular cells replicative DNA
    synthesis was increased in males.  When a higher dose was administered
    (1000 mg/kg body weight per day) marked decreases in the levels of
    plasma thyroxine and increased plasma thyroid stimulating hormone were
    observed.  None of these effects were observed in male Dunkin Hartley
    guinea-pigs, which were administered the chlorinated paraffin at doses
    of 500 and 1000 mg/kg body weight per day.  The LOEL in rats was 313
    mg/kg body weight per day based on increased relative liver weights,
    hepatic peroxisomal ß-oxidation and thyroxine-UDPG-glucuronosyl-
    transferase activity.

    c)  Mouse, 14-day studies

         B6C3F1 mice in groups of five were administered C10;60% Cl
    (CP-SH) in corn oil by gavage daily for 16 days (NTP, 1986a; Bucher et
    al., 1987).  The doses were 938, 1875, 3750, 7500 and 15 000 mg/kg
    body weight per day.  All mice receiving 3750 mg/kg or more, and 4/5
    males and 2/5 females receiving 1875 mg/kg died before the end of the
    study.  Diarrhoea was observed in all dosed groups except females
    receiving 938 mg/kg.  Enlarged livers were found in all treated
    surviving mice.  No histopathological examinations were conducted.

    d)  Mouse, 90-day studies

         B6C3F1 mice (10 of each sex per dose) were exposed to C12;60%
    Cl (CP-SH) by gavage five days per week for 13 weeks (NTP, 1986a;
    Bucher et al., 1987).  The doses were 125, 250, 500, 1000 or
    2000 mg/kg body weight per day.  No clinical signs of toxicity were
    observed.  In the males the body weight gain was reduced by 13% at the
    highest dose level.  The relative liver weights showed a dose-related
    increase (17-160%) and were statistically significant from 250 mg/kg
    in females and from 500 mg/kg in males.  Hepatocellular hypertrophy
    was observed in animals of both sexes treated with 250 mg/kg or more.
    Focal hepatic necrosis was related to dosing at 500, 1000 and
    2000 mg/kg in males and at 2000 mg/kg in females.  The NOEL was
    125 mg/kg body weight per day, and the LOEL was 250 mg/kg body weight
    per day, based on hepatocellular hypertrophy.

    7.2.1.2  Intermediate chain length chlorinated paraffins

    a)  Rat, 14-day studies

         A chlorinated paraffin of intermediate chain length (C14-17) and
    52% chlorination (CP-MH) was administered to Fischer-344 rats in the
    diet at dosage levels of 150, 500, 1500, 5000 and 15 000 mg/kg feed,
    which was reported to correspond to an average compound intake of

    17.7, 57.7, 177, 562 and 1412 mg/kg body weight per day (IRDC, 1981b). 
    Five male and five female rats in each dose group were exposed daily
    for 14 days.  No mortality occurred among the treated animals. 
    Hepatic APDM activity was statistically significantly increased in
    males receiving 562 mg/kg body weight per day (5000 mg/kg feed) and in
    females receiving 1412 mg/kg body weight per day (15 000 mg/kg feed). 
    Slight increase in cytochrome P-450 values in male rats given
    177 mg/kg body weight per day (1500 mg/kg feed) was observed but
    appeared not to be related to dosing.  Increased relative liver weight
    was observed in the highest two dosage groups.  Microscopic examination
    of the liver revealed mild diffuse hepatocellular hypertrophy in all
    animals receiving 562 and 1412 mg/kg body weight per day (5000 and
    15 000 mg/kg feed).  The NOEL was reported to be 57.7 mg/kg body weight
    per day.  The LOEL was 177 mg/kg body weight per day in males based on
    increased cytochrome P-450 values and 562 mg/kg body weight per day in
    females based on increased liver weight and hepatocellular hypertrophy.

    b)  Rat, 90-day studies

         Male and female weanling Sprague-Dawley rats in groups of ten
    were fed diets containing 0, 5, 50, 500 or 5000 mg/kg of C14-17;52%
    Cl(CP-MH) for 13 weeks, yielding an average intake of 0, 0.4, 3.6, 36
    and 360 mg/kg body weight per day for males and 0, 0.4, 4.2, 43 and
    420 mg/kg body weight per day for females (Poon et al., in press). 
    There were no clinical signs of toxicity and no differences in body
    weight gain.  Relative liver weight was increased at 43 and 420 mg/kg
    body weight per day in females and at 360 mg/kg in males.  Relative
    kidney weight was increased at the highest dose level in both sexes. 
    Serum cholesterol was increased in females from 4.2 mg/kg in a
    dose-related manner.  In the highest dose group of both sexes elevated
    hepatic UDP-glucuronosyltransferase activity was observed, but only
    females at this dose level showed increased APDM activity.  Decreased
    hepatic vitamin A levels were detected in females at 43 mg/kg and in
    both sexes at the highest dose level.  Mild, adaptive histopathological
    changes were detected in the liver of both sexes at the two highest
    dose levels, and in the thyroid of males from 36 mg/kg and females
    from 4.2 mg/kg (reduced follicle sizes, collapsed angularity,
    increased height, cytoplasmic vacuolation and nuclear vesiculation).
    In the kidney, minimal changes were noted in the proximal tubules of
    males at 360 mg/kg, and in the inner medulla tubules of females at 43
    and 420 mg/kg.  The NOEL in this study was 4 mg/kg body weight per day.
    The LOEL was 36 mg/kg body weight per day (males) and 43 mg/kg body
    weight per day (females).

         In a 90-day feeding study, Wistar rats (groups of 24 males and 24
    females) were fed diets containing 0, 250, 500, 2500 and 5000 mg/kg
    feed of Cereclor S52 (C14-17;52% Cl, CP-MH) containing stabilizer (0.2%
    epoxidized vegetable oil) (Birtley et al., 1980).  A dose-related
    decrease in body weight gain in males fed 500 mg/kg feed or more was

    observed, which was accompanied by a reduction in food intake. 
    Significant increases in the relative liver weights in females were
    observed at 500 mg/kg feed or more and in males at 2500 mg/kg feed. 
    Significant increases in relative kidney weights were observed at
    5000 mg/kg feed in both sexes.  Microscopic examination of the liver
    showed evidence of a dose-related proliferation of the smooth
    endoplasmic reticulum in the hepatic cells from 500 mg/kg feed.
    Haematological investigation showed no abnormalities attributable to
    the test compound.  A tendency towards congestion of the kidney with
    increasing concentration of Cereclor S52 in the diet was also observed.
    The NOEL was 250 mg/kg feed (12.5 mg/kg body weight per day based on
    food consumption data) and the LOEL was 500 mg/kg feed (25 mg/kg
    body weight per day) based on increased relative liver weights and
    proliferation of smooth endoplasmic reticulum.

         A medium chain length chlorinated paraffin (C14-17;52% Cl, CP-MH)
    was evaluated for subchronic toxicity in Fischer-344 rats (IRDC,
    1984b).  The chlorinated paraffin was administered to the rats (15 of
    each sex per dose group) in the diet to provide dosage levels of 0,
    10, 100 and 625 mg/kg body weight per day for 13 weeks.  The
    treatment did not induce signs of toxicity, alter survival or cause
    ophthalmological changes.  A slight reduction of body weight gain
    (< 5%) was observed in both sexes at the highest dose, and was
    associated with reduced food consumption.  Traces of hepatocyte
    hypertrophy (at 625 mg/kg) and increased absolute and relative liver
    and kidney weights (at 100 and 625 mg/kg) were noted in both sexes. 
    Males in the high-dose group had an increased incidence of nephritis. 
    In addition, increased thyroid weight and thyroid hypertrophy and
    hyperplasia were observed in males at 625 mg/kg.  The NOEL was
    considered in the report to be 10 mg/kg body weight per day.  The LOEL
    was 100 mg/kg body weight per day based on increased liver and kidney
    weights.

    c)  Dog, 90-day studies

         The effects of Cereclor S52 (C14-17;52% Cl, CP-MH) (containing
    0.2% epoxidized vegetable oil as stabilizer) were studied in Beagle
    dogs (Birtley et al., 1980).  Four male and four female animals in
    each group were fed a diet corresponding to 0, 10, 30 or 100 mg/kg
    body weight daily for 90 days.  No effects were found, except for
    significantly increased serum alkaline phosphatase activity and
    relative liver weight in males exposed to 100 mg/kg and an increase in
    the smooth endoplasmic reticulum of hepatocytes from 30 mg/kg.  The
    NOEL was 10 mg/kg body weight per day.  The LOEL was 30 mg/kg body
    weight per day based on an increase of hepatic smooth endoplasmic
    reticulum.

    7.2.1.3  Long chain length chlorinated paraffins

    a)  Rat, 14-16 day studies

         Fischer-344 rats (groups of five) were exposed to C22-26;43% Cl
    (CP-LL) daily by gavage for 16 days at doses of 235, 469, 938, 1875 or
    3750 mg/kg body weight per day.  No compound-related clinical signs
    of toxicity or mortality were observed.  There were no changes
    in body weight gain and no gross lesions were observed at necropsy. 
    Histopathological examinations were not conducted (NTP, 1986b; Bucher
    et al, 1987).

         Fischer-344 rats, in groups of five of each sex, were fed long
    chain length paraffins of 70% chlorination for 14 days.  The dietary
    concentrations of the C22-26;70% Cl (CP-LH) were 0, 150, 500, 1500,
    5000 and 15 000 mg/kg feed, corresponding to an average compound
    intake of 0, 17.1, 55, 169, 565 and 1715 mg/kg body weight per day
    (IRDC, 1982b).  Tissues from liver, kidneys, spleen, lungs and
    mesenteric lymph nodes were examined microscopically.  Hepatic
    microsomal Lowry protein, APDM activity and cytochrome P-450 values
    were determined.  No significant toxic effects were noted, and no
    compound-related effects were found after microscopical examinations. 
    The NOEL was 1715 mg/kg body weight per day.

         A chlorinated paraffin, C22-26;43% Cl (CP-LL), was administered by
    gavage to Charles River 344 rats at doses of 0, 30, 100, 300, 1000 and
    3000 mg/kg body weight per day (IRDC, 1982c).  During the 14-day test
    period no signs of toxicity were observed.  Following sacrifice,
    tissues from the liver, spleen, kidneys, pancreas, thymus and eyes
    were examined microscopically; the only observation was a possible
    increase in kidney nephrolithiasis in females exposed to the highest
    dose level.  Hepatic microsomal Lowry protein, APDM activity and
    cytochrome P-450 values were determined and there were no alterations. 
    The NOEL was considered to be 3000 mg/kg body weight per day.

    b)  Rat, 90-day studies

         A long chain length chlorinated paraffin, C23;43% Cl (CP-LL),
    was administered to Fischer-344 rats in groups of 10 (each sex) by
    gavage for 13 weeks at doses of 235, 469, 938, 1875 or 3750 mg/kg body
    weight per day (NTP, 1986b; Bucher et al., 1987). No effects on body
    or organ weights and no clinical signs of toxicity were observed.  A
    dose-related increased incidence of granulomatous inflammation was
    noted in the livers of all exposed female rats but not in males.  The
    NOEL was 3750 mg/kg body weight per day for males.  For females the
    LOEL was 235 mg/kg body weight per day based on increased incidence of
    granulomatous inflammation in the liver.

         A long chain chlorinated paraffin (C20-30) with 43% Cl (CP-LL) was
    administered in corn oil by gavage for 90 days to Fischer-344 rats at
    three doses (100, 900 or 3750 mg/kg body weight per day) (IRDC,
    1984f).  Increases in liver weights and a multifocal granulomatous
    hepatitis characterized by inflammatory changes and necrosis were
    observed in all exposed females but not in males.  In female rats
    mineralization in the kidneys at the highest dose level was observed. 
    In addition to these observations, mild nephrosis was observed in the
    males in the highest dose group.  In males, the NOEL was 900 mg/kg
    body weight per day and the LOEL was 3750 mg/kg body weight per day
    (based on the occurrence of mild nephrosis).  In females the LOEL was
    100 mg/kg body weight per day based on liver effects.

         The chlorinated paraffin C22-26;70% Cl (CP-LH) was administered to
    Fischer-344 rats in the diet for 90 days at doses of 100, 900 and
    3750 mg/kg body weight per day (IRDC, 1984g).  Increased liver weight,
    hepatocellular hypertrophy and cytoplasmic fat vacuolation were noted
    at the highest dose level.  The alanine aminotransferase (ALT)
    activity was increased in both sexes at the highest dose level, and
    aspartate aminotransferase (AST) activity was also increased in
    females of this group.  The NOEL was considered to be 900 mg/kg body
    weight per day.  The LOEL was 3750 mg/kg body weight per day based on
    liver effects.

    c)  Mouse, 14-16 day studies

         B6C3F1 mice in groups of five were given C22-26;43% Cl (CP-LL) by
    gavage daily for 16 days at doses of 469, 938, 1875, 3750 or
    7500 mg/kg body weight per day  (NTP, 1986b; Bucher et al., 1987).  No
    compound-related clinical sign of toxicity or mortality was observed,
    there were no changes in body weight gain, and no gross lesions were
    observed at necropsy.  Histopathological examinations were not
    conducted.

    d)  Mouse, 90-day studies

         The long chain length chlorinated paraffin C23;43% Cl (CP-LL)
    was administered to B6C3F1 mice (in groups of 10 of each sex) by
    gavage for 13 weeks at dose levels of 469, 938, 1875, 3750 or
    7500 mg/kg body weight per day (NTP, 1986b; Bucher et al., 1987).  No
    effects on body or organ weights, no clinical signs of toxicity and no
    histopathological effects were observed.  The NOEL was 7500 mg/kg body
    weight per day.

    7.2.1.4  Comparative studies

         The effects of representative chlorinated paraffins on liver
    function and thyroid hormone function has been studied in male rats
    (Alpk:APFSD) and male mice (Alpk:APFCD-1) (Wyatt et al., 1993). 
    Groups of five male rats or five male mice received 0, 10, 50, 100,

    250, 500 or 1000 mg/kg body weight per day by gavage in corn oil, once
    daily for 14 days.  The chlorinated paraffins studied were Chlorowax
    500C (C10-13;58%Cl, CP-SH), Cereclor 56L (C10-13;56%, CP-SH) and
    Chlorparaffin 40C (C14-17;40% Cl, CP-ML).  Effects on liver function
    were assessed by changes in liver weight (expressed both as absolute
    weights and liver:body weight ratio) and peroxisome proliferation
    (expressed as the activity of palmitoyl co-enzyme A (CoA) oxidase). 
    All three chlorinated paraffins caused increases in liver weight and
    palmitoyl CoA oxidation, indicative of peroxisomal proliferation.  In
    general, the rat was more sensitive to the effects of the chlorinated
    paraffins on liver weight than the mouse.  The doses of chlorinated
    paraffin required to cause peroxisomal proliferation were, in general,
    greater than those causing effects on liver weight, although there
    appeared to be less of a difference in inter-species sensitivity. 
    However, the magnitude of the increase in palmitoyl CoA oxidation
    caused by the short chain chlorinated paraffins (approximately 10-fold
    increase as a maximal change) was greater than for the intermediate
    chain grade (approximately 4-fold increase as maximal change) (Table
    18).  The effect of the chlorinated paraffins on thyroid function was
    studied in the male rats receiving 1000 mg/kg body weight per day for
    14 days by measuring the plasma levels of triiodothyronine (T3) and
    thyroxine (T4) (free and total) and thyroid stimulating hormone
    (TSH), and also the activity of hepatic microsomal UDP glucuronosyl-
    transferase activity.  All three chlorinated paraffins (at 1000 mg/kg
    body weight per day) caused a reduction in plasma T4 levels (both
    free and total) and an increase in plasma TSH levels.  No effect was
    observed on plasma T3 levels.  All three chlorinated paraffins also
    caused an increase (two-fold) in the rate of glucuronidation of T4
    by hepatic microsomal UDP glucuronosyltransferase activity, suggesting
    that the impact on plasma T4 and TSH levels is due to increased
    clearance of T4 by hepatic metabolism.

    Table 18.  Effects of chlorinated paraffins on liver function in male rats and male mice
               (From: Wyatt et al., 1993)

                                                                                                

                     Increase in relative liver weight      Increase in palmitoyl CoA
                     (% liver:body weight ratio)            oxidase activity
                                                                                                

                          Rat              Mouse               Rat              Mouse

                     NOELa   LOELb     NOELa   LOELb      NOELa   LOELb     NOELa   LOELb
                                                                                                

    C10-13;58% Cl    74      100       215     250        184     250       180     250

    C10-13;56% Cl    51      50        70      100        600     1000      120     250

    C14-17;40% Cl    31      100       426     1000       473     500       252     500
                                                                                                

    a    Calculated using a three-parameter logit model (mg/kg body weight per day)
    b    Observed (mg/kg body weight per day)
    
         The hepatic effects of representative chlorinated paraffins have
    been studied in male and female F-344 rats, male and female B6C3F1
    mice and male Alpk:Dunkin Hartley guinea-pigs (Elcombe et al., in
    press).  Their effects were compared with a range of known inducers of
    hepatic enzymes.  Groups of 4-5 animals received 1000 to 2000 mg/kg
    body weight per day of each chlorinated paraffin (by gavage in corn
    oil) for 14 consecutive days.  The chlorinated paraffins studied were
    Chlorowax 500C (C10-13;58% Cl, CP-SH), Cereclor 56L (C10-13;56% Cl,
    CP-SH), Chlorparaffin 40G (C14-17;40% Cl, CP-ML) and Chlorowax 40
    (C20-30;43% Cl, CP-LL).  The short and intermediate chain length
    chlorinated paraffins increased liver:body weight ratios (approximately
    1.5 times) and elicited hepatocellular hypertrophy, peroxisome
    proliferation (assessed as increases in peroxisomal volume and
    palmitoyl CoA oxidase activity) and proliferation of hepatic cell
    smooth endoplasmic reticulum in both rats and mice.  These effects
    were not seen in rats or mice receiving the long chain chlorinated
    paraffin.  The short and intermediate chain length chlorinated

    paraffins also caused induction of cytochrome P-450 IV A1 (assessed by
    increases in lauric acid hydroxylation) and P-450 II B1/IIB2 (assessed
    by increases in ethoxycoumarin- O-diethylation) in the rat liver, but
    only P-450 IV A1 in the mouse liver.  The induction of the specific
    cytochrome P-450 isoenzymes was confirmed using SOS-polyacrylamide gel
    electrophoresis (SPS-PAGE) and Western immunoblotting of microsomes.

         The administration of the short or intermediate chain length
    chlorinated paraffins to guinea-pigs (1000 mg/kg body weight per day
    for 14 days) had a similar effect on liver:body weight ratios (1.5-fold
    increase) but had no effect on any of the hepatic ultrastructural or
    biochemical parameters measured.

    7.2.2  Intraperitoneal route

    7.2.2.1  Short chain length chlorinated paraffins

         Effects on both hepatic cytosolic and microsomal epoxide
    hydrolases have been observed in male C57Bl/6 mice after 5 daily
    intraperitoneal injection of 400 mg Cereclor 70L (C12;70% Cl, CP-SH)
    (Meijer & DePierre, 1987).  The hepatic cytosolic epoxide hydrolase
    activity was increased to 130% and the microsomal activity to 250% of
    the control. In addition, the amount of microsomal cytochrome P-450
    was increased by 50%, and cytosolic DT-diaphorase activity was
    increased 2- to 3-fold.  There was also liver enlargement.

    7.2.2.2  Intermediate chain length chlorinated paraffins

         Lundberg (1980) reported a significant, dose-related increase in
    total cytochrome P-450 in mice (strain not reported) injected
    intraperitoneally with different amounts of Cereclor S52 (C14-17;52%
    Cl, CP-MH) (from 0.6 mg to 63.4 mg) on 3 consecutive days.  The
     N-demethylation of ethylmorphine, a cytochrome P-450-dependent
    reaction, decreased at low concentrations but increased at higher
    concentrations.

    7.2.2.3  Comparative studies

         Male Sprague-Dawley rats were given intraperitoneal injections of
    1000 mg/kg of Witaclor 149, 159 or 171P (C10-13 with 49% [CP-SL], 59%
    [CP-SH] and 71% [CP-SH] chlorination, respectively), Witachlor 350
    (C14-17 with 49% chlorination [CP-ML] or Witachlor 549 (C18-26 with 49%
    chlorination [CP-LL]), each containing small amounts of epoxidated
    soy-bean oil as stabilizer, daily for 4 days (Nilsen et al., 1980,
    1981; Nilsen & Toftgård, 1981).  Treatment with the C10-13 chlorinated
    paraffins, but not those with longer chain lengths, caused increases
    in liver weight and an induction of various forms of microsomal
    cytochrome P-450.  The activity of  O-deethylation of 7-ethoxyresorufin
    was decreased by the C10-13 chlorinated paraffins with higher
    chlorine content, Witaclor 159 and 171P. The metabolism of

    benzo (a)pyrene was induced by each of the chlorinated paraffins. 
    Witaclor 149 (C10-13;49% Cl) caused a significant proliferation of the
    smooth endoplasmic reticulum (two-fold) whereas C18-26;49% Cl caused a
    smaller increase.  All three C10-13 chlorinated paraffins gave rise to
    increased occurrence and size of cytoplasmic lipid droplets.  Witachlor
    149 also caused an increase in the number and size of mitochondria and
    peroxisomes.  These latter effects were also observed to a lesser
    degree with both Witachlor 350 and Witachlor 549.

         Effects on microsomal enzymes, after intraperitoneal injection of
    Cereclor 42 (C22-26;42% Cl, CP-LL), Cereclor S58 (C14-17;58% Cl, CP-MH),
    Cereclor 70 (C23;70% Cl, CP-LH) and Cereclor 70L (C10-13;70% Cl) (1000
    mg/kg, once daily for 5 days) in liver from male Sprague-Dawley rats,
    have been observed (Meijer et al., 1981).  Microsomal epoxide hydrolase
    activity was increased by all Cereclors except C22-26;42% Cl.  In
    addition, the activity of glutathione- S-transferase was increased
    except in the case of C22-26;42% Cl, which decreased the activity
    slightly.  The amount of cytochrome P-450 was not changed.

    7.3  Neurotoxicity

    7.3.1  Short chain length chlorinated paraffins

         The motor capacity, measured as the capacity of adult male NMRI
    mice to remain on an accelerating rotarod, was determined after single
    intravenous injections of 0, 30, 97.5, 165, 232.5 and 300 mg/kg in
    groups of five mice of either Cereclor 50 LV (C10-13;49% Cl, CP-SL) or
    Cereclor 70L (C10-13;70% Cl, CP-SH) (Eriksson & Kihlström, 1985).  A
    statistically significant decrease in the motor capacity and rectal
    temperature was observed in mice receiving the highest dose of either
    compound.

    7.3.2  Intermediate chain length chlorinated paraffins

         Immature 10-day-old NMRI mice (groups of at least 6) were given a
    single peroral dose of 1 mg/kg body weight of polychlorohexadecane
    (C16; chlorination degree not specified) dissolved in a fat emulsion
    of egg lecithin and peanut oil (Eriksson & Nordberg, 1986).  A
    significantly decreased sodium-dependent choline uptake in the
    cerebral cortex, 65% of Vmax in controls, was measured 7 days after
    treatment indicating a pre-synaptic effect of this chlorinated
    paraffin.  No significant alteration in high- and low-affinity
    muscarinic binding in the cerebral cortex in the brains could be
    observed.

    7.4  Reproductive toxicity, embryotoxicity and teratogenicity

    7.4.1  Reproduction

         An intermediate chain length chlorinated paraffin (C14-17) with
    52% chlorination (CP-MH) was given in the diet to Charles River rats
    at dose levels of 0, 100, 1000 and 6250 mg/kg feed (equivalent to 0,
    6, 62 and 384 mg/kg body weight per day for the males and 0, 8, 74 or
    463 mg/kg body weight per day for the females based on food
    consumption data) (IRDC, 1985).  The diet was fed both males and
    females for 28 days before mating, during mating, and for females up
    to postnatal day 21.  Pups were given the same diet from weaning
    until 70 days of age.  No differences were observed in appearance,
    fertility, body-weight gain, food consumption or reproductive
    performance in the F0 generation.  Among the offspring, no adverse
    effects were observed prior to lactation day 7.  However, significantly
    decreased pup survival was observed in the high-dose group on lactation
    day 10.  None of the pups in this group survived to weaning.  Survival
    in pups from the mid-dose group was decreased by lactation day 21.  
    Necropsy findings in animals that died included pale liver, kidneys and
    lungs, and blood in the cranial cavity, brain, stomach and intestines.
    The pup weights were lower in the low-dose group (not statistically
    significant) and mid-dose group than in the control group on lactation
    day 21.  In females, the reduced weight continued after weaning but
    became less pronounced in males.  Other observations in the pups of
    the mid- and high-dose groups included bruised areas, decreased
    activity, laboured breathing, pale discoloration and/or blood around
    orifices.  Reduced erythrocyte count, haemoglobin and haematocrit were
    noted in the pups in the high-dose group on lactation day 6 relative to
    the control values obtained on lactation day 7.  The observations in
    this study could indicate a high exposure of the pups to chlorinated
    paraffins via the milk.  This is supported by preliminary results of
    a cross-fostering study showing a greater mortality in pups exposed
    via milk than in pups exposed only  in utero (Serrone et al., 1987).
    The LOEL was 5.7 mg/kg body weight per day (males) or 7.2 mg/kg body
    weight per day (females) in the F1 generation based on decreased
    pup weight.

    7.4.2  Embryotoxicity and teratogenicity

         Teratology studies are summarized in Table 19.

        Table 19.  Oral teratology studies with chlorinated paraffins

                                                                                                                                      

    Chlorinated paraffina    Species   LOEL          NOEL          Effects and remarks                                   References
                                       (mg/kg        (mg/kg
                                       body weight   body weight
                                       per day)      per day)
                                                                                                                                      

    CP-SH:  C10-13;58% Cl    rat       2000          500           maternal toxicity at 500 and 2000 mg/kg body weight   IRDC (1982a)
                                                                   per day; embryo-fetotoxicity and digital
                                                                   malformations at 2000 mg/kg body weight per day

            C10-13;58% Cl    rabbit    -             100                                                                 IRDC (1982d)

    CP-MH:  C14-17;52% Cl    rat       -             5000          slight maternal toxicity at 2000 and 5000 mg/kg       IRDC (1984d)
                                                                   body weight per day

            C14-17;52% Cl    rabbit    -             100           mean maternal body weight losses were seen during     IRDC (1983f)
                                                                   treatment at the high-dose level (80, 100, 160 mg/kg
                                                                   body weight per day) in a range-finding study

            C14-17;70% Cl    mouse     -             100b                                                                Darnerud &
                                                                                                                         Lundkvist
                                                                                                                         (1987)
                                                                                                                                      

    Table 19 (Cont'd)

                                                                                                                                      

    Chlorinated paraffina    Species   LOEL          NOEL          Effects and remarks                                   References
                                       (mg/kg        (mg/kg
                                       body weight   body weight
                                       per day)      per day)
                                                                                                                                      

    CP-LL:  C20-30;43% Cl    rat       -             5000                                                                IRDC (1983d)

            C20-30;43% Cl    rabbit    -             2000          slight increase in mean implantation loss and         IRDC (1982e)
                                                                   decreased number of viable fetuses at 5000 mg/kg
                                                                   body weight per day, which were not statistically
                                                                   significant

    CP-LH:  C22-26;70% Cl    rat       -             5000                                                                IRDC (1984e)

            C22-26,70% Cl    rabbit    -             1000          possible maternal toxicity (non-dosage-related        IRDC (1983b)
                                                                   congestion of lungs). In preliminary rabbit studies
                                                                   an increase in post-implantation loss was observed
                                                                   at > 1000 mg/kg body weight per day, but this effect
                                                                   was not observed in the main teratology study
                                                                                                                                      

    a    The classification is given in Table 1
    b    Single intraperitoneal injection on day 1
        7.4.2.1  Short chain length chlorinated paraffins

         The teratogenic potential of a short chain length paraffin
    (C10-13) with 58% Cl (CP-SH) was studied in pregnant Charles River COBS
    CD rats (IRDC, 1982a).  The rats, in groups of 25, were administered
    0, 100, 500 and 2000 mg/kg body weight per day in corn oil orally by
    gavage once daily from days 6 to 19 of gestation, and were examined on
    gestation day 20.  In the dams, the high dose treatment increased the
    frequency of mortality (32%) and decreased body weight gain, and the
    mid- and high-dose treatments resulted in dose-related adverse
    clinical signs, such as yellow or brown matting and staining of the
    anogenital fur, soft stool, red or brown matter (or staining) in the
    nasal region, decreased activity, oily fur and excessive salivation. 
    Treatment at the highest dose level, which was a maternally toxic
    dose, resulted in the appearance of fetal malformations such
    as adactyly and/or shortened digits, increased incidences of
    postimplantation loss and decreased numbers of viable fetuses.  Fetal
    body weight and incidence of delayed bone ossification were not
    affected by the treatment.  The NOEL for teratogenic effects was
    500 mg/kg body weight per day, which was also a slightly maternally
    toxic dose.

         Female Dutch Belted rabbits (groups of 16) were treated by gavage
    with a short chain length chlorinated paraffin (C10-13) with 58%
    chlorination (CP-SH) (IRDC, 1982d).  The rabbits were treated at dose
    levels of 0, 10, 30 and 100 mg/kg body weight per day on gestation
    days 6-27 and examined on day 28.  There were no adverse effects on
    survival, body weight gain, clinical signs or postmortem observations
    in dams.  The highest-dose group had an increased incidence of whole
    litter resorption (two dams), and in the group exposed to 30 mg/kg
    slight increases in the incidence of whole litter resorption (one dam)
    and early and late resorptions were observed.  Whole litter
    resorptions did not occur in the low-dose or control animals, but
    occurred in historical controls at an incidence of 13/277.  This
    indicated that the appearance of one or two dams with whole litter
    resorptions could occur by chance.  The NOAEL in this study was
    100 mg/kg body weight per day.

    7.4.2.2  Intermediate chain length chlorinated paraffins

         Female Charles River COBS CD rats were treated by gavage with an
    intermediate chain length chlorinated paraffin (C14-17;52% Cl) (CP-MH)
    (IRDC, 1984d). The administered dose levels (0, 500, 2000 and
    5000 mg/kg body weight per day) were given to groups of 25 animals on
    gestation days 6-19, and this was followed by examination on day 20. 
    The end-points studied were weight of the uterus, number and location
    of viable fetuses, early and late resorptions, the number of total
    implantations and corpora lutea, and the incidence of fetal
    malformations.  The treatment had no adverse effect on mortality, body
    weight gain or uterine weight of dams, but signs of toxicity, such as

    wet, matted and yellow-stained hair in the anogenital area and/or soft
    stools, were observed in the mid- and high-dose dams.  No treatment-
    related adverse effects were observed in the fetuses and there was no
    evidence of developmental effects.

         Female Dutch Belted rabbits were treated by gavage with an
    intermediate chain length chlorinated paraffin (C14-17;52% Cl) (CP-MH)
    in groups of 16 (IRDC, 1983f).  The dose levels were 0, 10, 30 and
    100 mg/kg body weight per day and were administered on gestation days
    6-27, followed by examination on day 28.  The end-points studied were
    weight of the uterus, number and location of viable fetuses, early and
    late resorptions, the number of total implantations and corpora lutea,
    and the incidence of fetal malformations.  In the dams, congestion of
    the lobes of the lung was noted in all treated groups at necropsy, but
    did not occur in a dose-related pattern.  No significant adverse
    effects were observed in fetuses and there were no developmental
    effects.

         In a study of NMRI mice, the animals were given a single
    intraperitoneal injection of 100 mg/kg body weight of polychloro-
    hexadecane (C16;70% Cl) (CP-MH) on the day the vaginal plug was
    observed (day 1) (Darnerud & Lundkvist, 1987).  The mice were killed
    on day 14 of pregnancy, and the number and weight of embryos and
    resorptions were determined.  No effects on implantation or embryonic
    survival were observed.

    7.4.2.3  Long chain length chlorinated paraffins

         Groups of 25 pregnant Charles River COBS CD rats were administered
    (500, 2000 and 5000 mg/kg body weight per day) a long chain chlorinated
    paraffin (C22-26;43% Cl) (CP-LL) by gavage from days 6 to 19 of
    gestation (IRDC, 1983d).  The end-points studied were weight of the
    uterus, number and location of viable fetuses, early and late
    resorptions, the number of total implantations and corpora lutea,
    and the incidence of fetal malformations.  In the dams, there were no
    adverse effects on appearance, mean body weight gain or mortality
    rate, and necropsy findings were normal.  No signs of developmental
    effects were noted in the pups.

         Female Charles River COBS CD rats (groups of 25 animals)  were
    treated by gavage with a long chain length chlorinated paraffin
    (C22-26;70% Cl) (CP-LH) (IRDC, 1984e).  The dose levels were 0, 500,
    2000 and 5000 mg/kg body weight per day on gestation days 6-19.  The
    rats were examined on day 20.  The end-points studied were the same as
    in the previous study.  No treatment-related adverse effects were
    observed in the dams or pups.

         Pregnant Dutch Belted rabbits in groups of 16 were exposed orally
    to long chain chlorinated paraffin (C22-26;43% Cl) (CP-LL) at doses of
    500, 2000 and 5000 mg/kg body weight per day in corn oil by gavage
    once daily from days 6 to 27 of gestation (IRDC, 1982e).  The
    end-points studied were the same as in the previous studies in this
    section.  No effects on maternal survival or body weight gain
    occurred.  In the highest-dose group there was a slight increase in
    mean implantation loss and a slight decrease in the mean number of
    viable fetuses when compared to the control group.  However, these
    alterations were not statistically significant.  In the fetuses no
    alterations related to the treatment were observed, although the
    number in the highest-dose group was limited.  Treatment of the
    rabbits at a dose level of 2000 mg/kg body weight per day or less did
    not produce a teratogenic response.  No developmental effects were
    noted.  The NOEL in this study was 2000 mg/kg body weight per day.

         Female Dutch Belted rabbits (groups of 16 animals) were given by
    gavage a long chain length chlorinated paraffin (C22-26;70% Cl) (CP-LH)
    (IRDC, 1983b).  Doses of 0, 100, 300 and 1000 mg/kg body weight per
    day were administered on gestation days 6-27, followed by examination
    on day 28.  The end-points studied were the same as in the earlier
    studies in this section.  The appearance, behaviour and body weight
    gain were normal in the treated dams, although at necropsy a
    non-dose-related increase in the occurrence of congested lungs was
    noted.  No adverse effects on the fetuses were observed and no
    developmental effects were noted.

    7.5  Mutagenicity and related end-points

         Chlorinated paraffins do not appear to induce mutations in
    bacteria.  However, in mammalian cells there is a suggestion of a weak
    clastogenic potential  in vitro but not, according to several reports,
     in vivo.  Chlorinated paraffins were also reported to induce cell
    transformation  in vitro.


        Table 20.  Mutagenicity of chlorinated paraffins in bacterial tests

                                                                                                                                      

              Chlorinated paraffina                  Dose (µg/plate)   S9    Bacterial strainsb    Effects    Reference
                                                                                                                                      

    Cereclor 50LV           C10-13;50% Cl (CP-SH)    2500              ±     TA1535                -          Birtley et al. (1980)
                                                                             TA1538                -
                                                                             TA100                 -
                                                                             TA98                  -

    Hordalub 80 (with 1%    C10-13;50% Cl (CP-SH)    10 000            ±     TA98                  +          Hoechst (1986a)
    epoxy stabilizer)                                                        TA100                 -
                                                                             TA1535                -
                                                                             TA1537                -
                                                                             TA1538                -
                                                                             WP2 uvrAc             -

    Chloroparaffin 56       C12;57% Cl (CP-SH)       5000              ±     TA98                  -          Hoechst (1988)
    (unstabilized)                                                           TA100                 -
                                                                             TA1535                -
                                                                             TA1537                -
                                                                             TA1538                -
                                                                             WP2 uvrAc             -

    Cereclor 70L            C10-13;70% Cl (CP-SH)    2300              ±     TA98                  -          Meijer et al. (1981)
                                                                             TA100                 -
                                                                             TA1537                -

    Cereclor S52            C14-17;52% Cl (CP-MH)    2500              ±     TA1535                -          Birtley et al. (1980)
      - stabilizer                                                           TA1538                -
                                                                             TA100                 -
                                                                             TA98                  -
      + stabilizer                                                                                 -
                                                                                                                                      

    Table 20.  Cont'd

                                                                                                                                      

              Chlorinated paraffina                  Dose (µg/plate)   S9    Bacterial strainsb    Effects    Reference
                                                                                                                                      

    Solvocaffaro C1642      C14-17;42% Cl (CP-ML)    1, 10,            ±     TA1535                -          Conz & Fumero (1988a)
                                                     100,                    TA1537                -
                                                     1000,                   TA1538                -
                                                     5000                    TA98                  -
                                                                             TA199                 -

    Meflex DC 029           C14-17;45% Cl (CP-ML)    1.6, 8,           ±     TA1535                -          Elliott (1989a)
                                                     40,                     TA1537                -
                                                     200,                    TA1538                -
                                                     1000,                   TA98                  -
                                                     5000                    TA1000                -

    Cereclor 42             C20-30;42% Cl (CP-LL)    2500              ±     TA1535                -          Birtley et al. (1980)
                                                                             TA1538                -
                                                                             TA100                 -
                                                                             TA98                  -

    Chorowax 40             C23;43% Cl (CP-LL)       10 000            ±     TA97                  -          NTP (1986b)
                                                                             TA98                  -
                                                                             TA100                 -
                                                                             TA1535                -
                                                                                                                                      

    a    The classification is given in Table 1
    b    Unless indicated otherwise, all strains refer to  Salmonella typhimurium
    c    Strain of  Escherichia coli
        7.5.1  Prokaryotes

         Most of the data demonstrate no mutagenic effects in four
     Salmonella typhimurium strains after treatment with short,
    intermediate or long chain length chlorinated paraffins at doses up to
    10 mg/plate (Table 20).  A very low but significant effect was
    detected in strain TA98 after treatment with the highly chlorinated
    short chain length chlorinated paraffin, Cereclor 70L (C10-12;70% Cl,
    CP-SH) (Meijer et al., 1981).  However, the observation is uncertain
    since no dose response was observed, the increase in revertants was
    low (less than 2-fold), and the increase was only found in the
    presence of metabolic fraction (S9) derived from Aroclor-1254-induced
    rat liver.  The results from this study were considered to be
    negative.  Another study apparently demonstrated positive results. 
    However, the increase in the number of revertants with TA100 in the
    presence of S9 was just less than two-fold, and in TA98, in the
    absence of S9, the increase only just reached two-fold (Hoechst,
    1986a).  Furthermore, the possibility that the epoxy stabilizer was
    responsible for the increase can not be discounted.

    7.5.2  Mammalian cells

         The results obtained from mammalian cell systems are summarized
    in Tables 21, 22 and 23.

    7.5.2.1  In vitro studies

         C12;60% Cl (CP-SH) was mutagenic in L5178Y mouse lymphoma cells
    at concentrations of 48 and 60 µg/ml in the absence of S9 mix (Myhr et
    al., 1990).

         When tested up to cytotoxic concentrations, C10-13;56% Cl(CP-SH)
    did not induce a significant, reproducible increase in the number of
    mutant colonies in Chinese hamster V79 cells (HPRT locus), either in
    the presence or absence of S9.

         Chlorowax 500C (C23;43% Cl, CP-LL) induced chromosome
    aberrations in the absence of S9 mix at a concentration of 5000 µg/ml
    and sister chromatid exchange (SCE) with and without S9 at 5, 500,
    1700 and 5000 µg/ml in Chinese hamster ovary (CHO) cells  in vitro
    (Anderson et al., 1990).

    7.5.2.2  In vivo studies

    a)  Short chain length chlorinated paraffins

         When C12;60% Cl (CP-SH) (0, 500, 1000 and 2000 mg/kg body weight
    was administrated in corn oil by gavage to Alpk:AP male rats (groups
    of 4), no effects on unscheduled DNA synthesis (UDS) in hepatocytes
    could be detected after exposure for 2 or 12 h (Ashby et al., 1990). 
    However, a moderate dose- and time-related induction of cell
    proliferation, measured as S-phase cells, in the hepatocytes was
    detected in animals exposed to 1000 and 2000 mg/kg for 12 h.
        Table 21.  Genotoxicity in mammalian cells  in vitro

                                                                                                                                      

    Chlorinated paraffin     Cell line          End-point           Exposure                           Effect         References
                                                                                                                                      

    CP-SH:  C10-13;56% Cl    Chinese hamster    mutations           5, 10, 15, 20, 30, 50, 75 µg/ml    -              Hoechst (1987)
                             V79 cells                              (±S9)

            C12;60% Cl       L5178Y mouse       mutations           12, 24, 36, 48, 60 and 72 µg/ml    + (from        Myhr et al.
                             lymphoma cells                         (-S9)                              60 µg/ml)      (1990)

    CP-LL:  C23;43% Cl       Chinese hamster    chromosome          1250-5000 µg/ml (±S9)              + (at 5000     Anderson et al.
                             ovary cells        aberrations                                            µg/ml + S9)    (1990)

            C23;43% Cl       Chinese hamster    sister chromatid    5, 500, 1700 and 5000 µg/ml        +a             Anderson et al.
                             ovary cells        exchange            (±S9)                                             (1990)
                                                                                                                                      

    a    The effect was observed at all concentrations

    Table 22.  Cell transformation in  in vitro mammalian cells

                                                                                                                                      

    Grade                    Cell line                    Exposure                                   Effect   References
                                                                                                                                      

    CP-SH:  C10-13;50% Cl    Baby hamster kidney cells    0.25, 2.5, 25, 250 and 2500 µg/ml (-S9)    -        Birtley et al. (1980)

            C10-13;58% Cl    Baby hamster kidney cells    44 µg/ml (-S9), 58 µg/ml (+S9)             +        ICI (1982a)

            C10-13;58% Cl    Baby hamster kidney cells    33 µg/ml (-S9), 88 µg/ml (+S9)             +        Richold et al. (1982a)

    CP-MH:  C14-17;52% Cl    Baby hamster kidney cells    0.25, 2.5, 25, 250 and 2500 µg/ml (-S9)    -        Birtley et al. (1980)

    CP-LL:  C20-30;42% Cl    Baby hamster kidney cells    0.25, 2.5, 25, 250 and 2500 µg/ml (-S9)    -        Birtley et al. (1980)

    CP-LH:  C20-26;70% Cl    Baby hamster kidney cells    10, 50, 100, 500 and 1000 µg/ml (±S9)      +a       Richold et al. (1982b)

            C22-26;70% Cl    Baby hamster kidney cells    10 µg/ml (+S9), 294 µg/ml (-S9)            +        ICI (1982b)
                                                                                                                                      

    a    The effect was observed at all concentrations

    Table 23.  Genotoxicity data from  in vivo mammalian cells

                                                                                                                                      

    Grade             Species and     End-point                Exposure                              No. of   Effect   References
                      strain                                                                         animals
                                                                                                                                      

    CP-SH:            Fischer-344     Chromosome aberrations   250, 750 and 2500 mg/kg body weight   8        -        IRDC (1983h)
      C10-12,58% Cl   rats            in bone marrow cells     per day for 5 days by gavage

      C10-13,58% Cl   Charles River   Dominant lethal          250, 750 and 2500 mg/kg body weight   15       -        IRDC (1983a)
                      COBS CD rats    mutations                per day for 5 days by gavage

      C10-13,58% Cl   NMRI mice       Micronucleus assay       50, 5000 mg/kg body weight (single    10       -        Muller (1989)
                                      in bone marrow cells     dose by gavage)

      C10-13,58% Cl   Hoe:NMRKF       Micronucleus assay       50, 5000 mg/kg body weight (single    10       -        Muller (1989)
                      SPF 71 mice     in bone marrow cells     dose by gavage)

      C12;60% Cl      Alpk: AP rats   DNA repair in            500, 1000 and 2000 mg/kg body weight  4        -        Ashby et
                                      hepatocytes              by gavage (single dose by gavage)                       al. (1990)
                                                               for 2 or 12 h

    CP-ML:            Crd: CD-1       Micronucleus assay       5000 mg/kg body weight (single dose   10       -        Conz &
      C14-17;42% Cl   (ICR) Br mice   in bone marrow cells     by gavage)                                              Fumero (1988b)

      C14-17;45% Cl   C57B1/6JFCD-1/  Micronucleus assay       3125, 5000 mg/kg body weight (single  10       -        Elliott
                      Alpk mice       in bone marrow cells     dose by gavage)                                         (1989b)
                                                                                                                                      

    Table 23.  (Cont'd)

                                                                                                                                      

    Grade             Species and     End-point                Exposure                              No. of   Effect   References
                      strain                                                                         animals
                                                                                                                                      

    CP-MH:            Fischer-344     Chromosome aberrations   500, 1500 and 5000 mg/kg body weight  8        -        IRDC (1983g)
      C14-17;52% Cl   rats            in bone marrow cells     per day for 5 days by gavage

    CP-LL:            Fischer-344     Chromosome aberrations   500, 1500 and 5000 mg/kg body weight  8        -        IRDC (1983i)
      C22-26;43% Cl   rats            in bone marrow cells     per day for 5 days by gavage

    CP-LH:            Fischer-344     Chromosome aberrations   500, 1500 and 5000 mg/kg body weight  8        -        IRDC (1983e)
      C20-30;70% Cl   rats            in bone marrow cells     per day for 5 days by gavage
                                                                                                                                      
             Sexually mature male Fischer-344 rats in groups of eight were
    dosed by gavage once daily for 5 days with a short chain length 
    chlorinated paraffin (C10-12;58% Cl, CP-SH) at doses of 0, 250, 750 or
    2500 mg/kg body weight per day (IRDC, 1983h).  Metaphase spreads of
    rat bone marrow cells were examined for chromosome aberrations.  In
    the group treated with 2500 mg/kg, all the rats except one died during
    the study.  Signs of overt toxicity were observed in most of these
    rats.  The rats receiving up to 750 mg/kg body weight per day did not
    show an increased mortality or frequency of chromosome or chromatid
    abnormalities, neither did the surviving rat from the highest dose
    group.  These observations indicate that toxic doses were administered
    to the rats.  Cytotoxicity was not assessed.  However, the information
    on distribution of short chain chlorinated paraffins following oral
    absorption (section 6.3.1) indicates that there would have been
    distribution to the bone marrow.  This chlorinated paraffin was not
    considered clastogenic in this test system.

         Sexually mature NMRI (Hoe, NMRKF [SPF71]) mice (groups of five
    males and five females) were given  single doses of 50 and 5000 mg/kg
    body weight Chlorowax 500C (C10-13;58% Cl, CP-SH) by gavage in sesame
    oil (Hoechst, 1989).  Responses at the high dose level were examined
    at 24, 48 and 72 h sampling times and the low dose level at a 24 h
    sampling time only.  There were no differences from control values
    either in polychromatic cells with micronuclei or in the ratio of
    polychromatic erythrocytes to normocytes.

         The dominant lethal mutation potential of a chlorinated paraffin
    of short chain length and 58% chlorination was examined in Charles
    River COBS CD rats (IRDC, 1983a).  Groups of 15 males were treated
    with 0, 250, 750 and 2000 mg/kg body weight per day in corn oil orally
    by gavage for five consecutive days.  Each male was then mated with 20
    untreated females.  There was no evidence of a mutagenic effect on the
    post-meiotic stage of spermatogenesis at any dose level, as shown by
    the absence of effect on the mean number of viable embryos during the
    first four weeks of mating.

    b)  Intermediate chain length chlorinated paraffins

         Sexually mature male Fischer-344 rats in groups of eight were
    given unstabilized chlorinated paraffin (C14-17;52% Cl, CP-MH) in corn
    oil by gavage once daily for 5 days at doses of 0, 500, 1500 and 5000
    mg/kg body weight per day (IRDC, 1983g).  Metaphase spreads of rat
    bone marrow cells were examined for chromosome aberrations.  No signs
    of toxicity were observed during the study, and the treatments did not
    produce any increase in the frequency of chromosome abnormalities,
    compared to the controls.

         Two studies yielding negative results in the mouse bone marrow
    micronucleus assay have been reported.  Sexually mature mice, of
    strains CRI: CD-1 (ICR) BR (Conz & Fumero, 1988b) and C57BL/6JF
    CD-1/ALpK (Elliott, 1989b) were used.  Conz & Fumero (1988b) studied
    Solvocaffaro C1642 (C14-17;42% Cl (CP-MH)) and Elliott (1989b) studied
    Melex DC 029 (C14-17;45% Cl).  In both studies groups of 10 animals:
    (five males and five females) were given the limit dose of 5000 mg/kg
    body weight by gavage in corn oil.  Elliott (1989b) also used a lower
    dose of 3125 mg/kg body weight.  Responses at 5000 mg/kg were examined
    at three sampling times (18, 43 and 66 h (Conz & Fumero, 1988b) or 24,
    48 and 72 h (Elliott, 1989b)).  Responses at the lower dose level
    (Elliott, 1989b) were examined at 24 h.  In both studies there were no
    differences from negative control values in either polychromatic cells
    with micronuclei or in the ratio of polychromatic erythrocytes to
    normocytes.  The positive control (mitomycin C [8 mg/kg body weight,
    Conz & Fumero, 1988b] or cyclophosphamide [65 mg/kg body weight,
    Elliott, 1989b]) produced the anticipated positive responses, thus
    verifying the sensitivity of the test systems.

    c)  Long chain length chlorinated paraffins

         When a long chain length paraffin with 70% chlorination (CP-LH)
    (in 1% carboxymethylcellulose) was administered by gavage to
    Fischer-344 rats (groups of 8) at doses of 500, 1500 and 5000 mg/kg
    body weight daily for 5 days, no increased frequency of chromosome
    abnormalities in bone marrow cells was observed indicating a lack of
    clastogenic activity under the experimental conditions (IRDC, 1983e). 
    Body weight gain was decreased in the high-dose group.

         Sexually mature male Fischer-344 rats in groups of eight were
    given (gavage once daily for 5 days) a long chain length chlorinated
    paraffin (C22-26;43% Cl, CP-LL) at doses of 500, 1500 and 5000 mg/kg
    body weight per day (IRDC, 1983i).  Metaphase spreads of rat bone
    marrow cells were examined for chromosome aberrations.  No signs of
    toxicity was observed during the study, and the treatment did not
    produce any increase in the frequency of chromosome abnormalities,
    compared to the controls.

    7.5.2.3  Cell transformation

         Chlorowax 500C (C10-13;58% Cl, CP-SH), was examined in a cell
    culture transformation test using baby hamster kidney (BHK) cells in
    soft agar (Richold et al., 1982a).  The cells were treated with doses
    from 3.125 µg/ml to 500 µg/ml (-S9) and from 6.25 µg/ml to 1000 µg/ml
    (+S9). Treatment with LC50 doses of 33 µg/ml (-S9) and 88 µg/ml (+S9)
    increased the transformation frequency 52 times in the absence of S9
    (the control was negative at 50% simulated survival) and 500 times in
    the presence of S9.

         Cereclor 50LV (C10-13;50% Cl, CP-SH) was not active at dose levels
    up to 2500 µg/ml in a cell transformation assay using BHK cells
    (Birtley et al., 1980).

         Cereclor S52 (C14-17;52% Cl, CP-MH) with or without stabilizer 
    did not induce transformation of BHK cells at doses up to 2500 µg/ml
    (Birtley et al., 1980).

         After treatment of BHK cells with a long chain length paraffin
    Electrofine S-70 (C20-26;70% chlorination, CP-LH) in doses from
    10 µg/ml to 1000 µg/ml (+S9), a dose-related increased frequency of
    transformed colonies was demonstrated at all dose levels (Richold et
    al., 1982b).

         Cereclor 42 (C20-30;42% Cl, CP-LL) was not active at dose levels
    up to 2500 µg/ml in a cell transformation assay in BHK cells (Birtley
    et al., 1980).

    7.6  Long-term exposure and carcinogenicity

    7.6.1  Oral route

    7.6.1.1  Short chain length chlorinated paraffins

         In a 2-year gavage study using Fischer-344 rats, groups of 50
    males and 50 females were given C12;60% Cl, CP-SH at doses of 312 or
    625 mg/kg per day, 5 days/week, for 104 weeks) (NTP, 1986a; Bucher et
    al., 1987).  After week 37, the body weights of the high-dose males
    were reduced by 10-23% compared with controls.  Survival of both
    low- and high-dose males and of low-dose females was significantly
    less than that of controls (at termination 27 male controls, 6
    low-dose and 3 high-dose males and 34 control females, 23 low-dose and
    29 high-dose females survived).  Additional groups of 20 male and 20
    female rats were added to each dose group for concurrent 6-month and
    12-month studies.  The spleen, liver, thymus, adrenal glands, brain,
    kidney and heart were weighed at necropsy in the 6- and 12-month
    studies.  Biochemical and haematological effects were not examined.

         The incidence of tumours, which was significantly increased, is
    presented in Table 24.  Liver neoplastic nodules and hepatocellular
    carcinomas combined in males and females occurred with a positive
    trend.  The incidence of kidney tubular cell adenomas and the combined
    incidence of adenomas and adenocarcinomas were significantly increased
    in low-dose male rats.  In low-dose females an increased incidence of
    thyroid follicular cell adenomas was observed, and in addition,
    adenomas and carcinomas combined showed an increased incidence in
    high-dose female rats.  Increased incidences of mononuclear cell

    leukaemia, pancreatic acinar cell adenomas and endometrial stromal
    polyps of the uterus (low-dose female rats) were observed.  The
    increased incidence of mononuclear cell leukaemia was dose-related in
    males but not in females.  Although the incidence of endometrial
    stromal polyps in the low-dose female rats was greater than in vehicle
    controls, these tumours were probably not treatment-related since
    there were no increases at higher doses.  The incidence of pancreatic
    acinar tumours was also increased in the low-dose group of males,
    although, owing to the higher incidence in concurrent compared to
    historical controls and the absence of a dose-response relationship,
    the increase was not considered to be treatment-related.

         In the same study some chronic non-neoplastic lesions were
    reported.  Hepatocellular hypertrophy was observed in 74% of the
    low-dose group and in nearly all of the high-dose rats, but in none
    of the control group.  Necrosis and angiectasis were observed in the
    livers in all dosed rats.  In addition to increased kidney weight at 6
    and 12 months in both sexes and dose levels, the incidence and
    severity of nephropathy was increased in dosed females, as was the
    severity of nephropathy in males in the concurrent 12-month study. 
    Erosion, inflammation and ulceration of the glandular stomach and the
    forestomach were seen in both groups of the dosed males.  Hyperplasia
    of the parathyroid was observed in both groups of exposed males and in
    high-dose females.

         Groups of 50 male and 50 female B6C3F1 mice were given C12;60%
    Cl, CP-SH by gavage at doses of 125 and 250 mg/kg 5 days a week for
    103 weeks (NTP, 1986a; Bucher et al., 1987).  The body weights of
    treated females were about 10% lower than those of controls during the
    second year.  The survival of treated males was not significantly
    different from that of the controls, but in the high-dose group of
    females fewer animals were still alive after week 100 in comparison
    with the control group.  The tumour incidences are shown in Table 25. 
    Increased incidences of liver adenomas and liver adenomas and
    carcinomas in combination were observed.  The incidences of thyroid
    follicular cell adenomas and carcinomas combined were increased in
    exposed female mice.  The incidences of alveolar/bronchiolar
    carcinomas were increased significantly in the high-dose group of male
    mice, and the trend with dose was also significant.  However, the
    incidences of alveolar/bronchiolar carcinomas and adenomas (combined)
    in males were not significantly greater than those in vehicle
    controls.  Among the non-neoplastic lesions, the incidence of
    nephrosis was increased in the high-dose group of females, but was
    decreased in dosed male mice compared to controls. Biochemical and
    haematological effects were not examined.

        Table 24.  Incidence of tumours in rats administered the chlorinated paraffin C12;60% chlorine
               (From: NTP, 1986a; Bucher et al., 1987)

                                                                                                                                      

    Dose            Hepatocellular    Hepatocellular    Hepatocellular        Follicular cell    Mononuclear        Adenomas or
    (mg/kg          neoplastic        carcinomas        neoplastic nodules    adenomas and       cell leukaemia     adeno-carcinomas
    body weight)    nodules                             and carcinomas        carcinomas of                         of the kidney
                                                                              the thyroid
                                                                                                                                      

    Males
      Control       0/50              0/50              0/50                  3/50               7/50               0/50
      312           10/50a            3/50a             13/50a                3/50               12/50b             9/50b
      625           16/48a            2/48              16/48a                3/50               14/50b             3/49

    Females
      Control       0/50              0/50              0/50                  0/50               11/50              0/50
      312           4/50              1/50              5/50a                 6/50a              22/50b             0/50
      625           7/50a             1/50              7/50a                 6/50a              16/50              0/50
                                                                                                                                      

    a    Incidental tumour test for trend, p < 0.05, increase relative to control
    b    Life table analysis, p < 0.05, increase relative to control
            Table 25.  Incidence of tumours in mice administered the chlorinated paraffin
               C12;60% chlorine (From: NTP, 1986a; Bucher et al., 1987)

                                                                                                

    Dose         Hepatocellular     Hepatocellular     Hepatocellular     Follicular cell
    (mg/kg       adenomas           carcinomas         adenomas and       adenomas and
    body                                               carcinomas         carcinomas of
    weight)                                                               the thyroid
                                                                                                

    Males
      Control    11/50              11/50              20/50              3/49
      125        20/50a             15/50              34/50a             4/50
      250        29/50a             17/50              38/50a             3/49

    Females
      Control    0/50               3/50               3/50               8/50
      125        18/50a             4/50               22/50a             12/49a
      250        22/50a             9/50b              28/50a             15/49a
                                                                                                

    a    Incidental tumour test for trend, p < 0.05, increase relative to control
    b    Life table analysis, p < 0.05, increase relative to control
    
    7.6.1.2  Long chain length chlorinated paraffins

         Groups of 50 male and 50 female Fischer-344 rats were treated by
    gavage with 1875 and 3750 mg/kg body weight (male rats) and 100, 300
    and 900 mg/kg body weight (female rats) of C23;43% Cl, CP-LL
    dissolved in corn oil on 5 days a week for 103 weeks (NTP, 1986b;
    Bucher et al., 1987).  The treatment did not affect body weight or
    survival, and no signs of clinical toxicity were observed.  Additional
    groups of 20 male and 20 female rats were exposed concurrently to the
    same doses for 6 or 12 months for analyses of the weights of the
    spleen, liver, thymus, adrenal glands, brain, kidneys and heart, serum
    hepatic enzymes, including sorbitol dehydrogenase, AST and ALT, and
    haematological parameters.

         In female rats that were administered the chlorinated paraffin,
    an increased incidence of adrenal gland medullary phaeochromocytomas
    was observed (1/50; 4/50; 6/50; 7/50, high dose statistically
    significant, significant positive trend).  In addition, an increased
    incidence of endometrial stromal polyps in the uterus was found in the
    low-dose group of the females, but this increase was not dose-related
    (9/50; 17/50; 10/50; 10/50, low dose statistically significant) (Table
    26).  In males, acinar cell tumours of the pancreas occurred with a
    negative trend.  The incidence of benign hepatocellular neoplasia was
    not increased in dosed rats.

    Table 26.  Incidence of tumours in rats administered C23;43% Cl
               (From: NTP, 1986b; Bucher et al., 1987)

                                                                      

    Dose (mg/kg body     Adrenal medulla,        Uterus, endometrial
    weight)              phaeochromocytomas      stromal polyps
                                                                      

    Females
        0                     1/50                     9/50
        100                   4/50                     17/50a
        300                   6/50                     10/50
        900                   7/50a                    10/50
                                                                      

    a    Incidental tumour test for trend, p < 0.05, increased relative
         to control

         Several non-neoplastic lesions were related to the administration
    of C23;43% Cl.  Relative liver weights were increased in exposed
    males at 12 months and in exposed females at 6 and 12 months.  The
    observed increases were dose-related.  Activities of several serum
    enzymes were also slightly elevated at both 6 and 12 months.  There
    were also variations in haematological parameters at 6 and 12 months,
    but only in females.  The primary non-neoplastic lesion related to
    administration of this chlorinated paraffin included a diffuse
    lymphohistiocytic inflammation in the liver and in the pancreatic and
    mesenteric lymph nodes in male and female rats in all exposed groups. 
    Splenic congestion was a secondary effect.

         Groups of 50 male and 50 female B6C3F1 mice were given, by
    gavage, C23;43% Cl, CP-LL dissolved in corn oil at doses of 2500 and
    5000 mg/kg on 5 days a week for 103 weeks (NTP, 1986b; Bucher et al.,
    1987).  The survival of the mice was not significantly different in
    treated groups compared to controls, and there were no clinical signs
    of toxicity.  However, in the female groups a  Klebsiella infection
    affected the animals after week 65, and 60 to 70% of the early deaths
    in each group were attributed to the infection. Low-dose males and
    females had lower weight gains than control or high-dose groups.  The
    incidence of malignant lymphomas was significantly increased in males
    of the high-dose group, and occurred with a positive trend (Table 27). 
    The incidences of hepatocellular carcinomas in females occurred with a
    positive trend, but the increase was not significant.  The incidences
    of adenomas and carcinomas of the liver (combined) were marginally
    increased in females.  Follicular cell carcinomas in males occurred
    with a positive trend (0/49; 0/48; 3/49) in the thyroid gland. 
    However, the incidence of follicular cell adenomas or carcinomas
    (combined) was not significantly greater than that in vehicle controls
    (1/49, 3/48; 5/49) and was within the range of historical controls for
    the test laboratory.  No significant increases in non-neoplastic
    lesions were attributed to administration in mice.

    Table 27.  Incidence of tumours in mice administered C23;43% Cl
               (From: NTP, 1986b; Bucher et al., 1987)

                                                                      

    Dose (mg/kg      Lymphoma      Hepatocellular      Hepatocellular
    body weight)                   carcinomas          adenomas and
                                   carcinomas
                                                                      

    Males
      0                6/50            9/50                18/50
      2500             12/50           12/50               21/50
      5000             16/50a,b        12/50               23/50

    Females
      0                15/50           1/50                4/50
      2500             12/49           1/49                3/49
      5000             20/50           6/50                10/50
                                                                      

    a    Incidental tumour test for trend, p < 0.05, increased relative
         to controls
    b    Life table test, p < 0.05, increased relative to controls

    8.  EFFECTS ON HUMANS

    8.1  General population exposure

    8.1.1  Controlled human studies

         Chlorinated paraffins C10-13;50 and 63% Cl(CP-SH) were applied,
    under occlusive dressings, to the upper arm of 26 volunteers
    (INVERESK, 1975).  After 24 h the applications were removed and one
    hour later skin reactions were examined by two independent assessors. 
    A second application was made and reactions were assessed after a
    further 24 h contact.  Mild erythema and dryness (average scores, read
    at the 24 and 50 h time points, of less than 2 and 1, respectively, on
    a 4-point scale) were recorded, which were comparable to scores in a
    liquid paraffin control group.

         Paroil 142 (C20-30;40-41% Cl, CP-LL) and Chlorez 700 (C24;70% Cl,
    CP-LH) were applied to the skin of 200 male and female volunteers for
    a 5-day period, then reapplied for 2 days beginning 3 weeks after the
    initial exposure. The dose level was not reported.  No primary local
    irritation, allergic response or other toxic responses were observed. 
    In a similar study, Chlorowax 70 (C24;70% Cl, CP-LH), Chlorowax 500C
    (C12;59% Cl, CP-SH) and Chlorowax 40 (C24;43% Cl, CP-LL) were applied
    to the skin of 200 males and female volunteers.  The exposure time
    period and amount of chlorinated paraffins used were not reported. 
    The treatments did not produce local irritation or allergic responses
    (Howard et al., 1975).

    8.2  Occupational exposure

         In a study on cutting fluid coolants, 134 non-exposed employees
    and 75 exposed employees were patch tested with various constituents
    of the cutting fluids including chlorinated paraffins (Menter
    et al., 1975).  No positive reactions were obtained with any of the
    constituents, although the authors themselves suggested that the tests
    were not sufficiently stringent, as some positive reactions were
    anticipated for some of the constituents tested.

         Positive skin reactions to chlorinated paraffin constituents were
    obtained in patch tests conducted on four employees suffering from
    scaly eczema, who had been exposed occupationally to cutting oils
    (English et al., 1986). However, the authors concluded that the
    reaction was due to additives in the cutting oil, which showed
    positive reactions when tested alone, rather than to the chlorinated
    paraffin.

    9.  EFFECTS ON OTHER ORGANISMS IN THE LABORATORY AND FIELD

    9.1  Laboratory experiments

    9.1.1  Microorganisms

         The inhibition of gas production in an anaerobic sewage sludge
    digestion process by C10-12;58% Cl (CP-SH) was studied by Madeley et
    al. (1983b).  A significant (> 10%) inhibition of gas production
    occurred at chlorinated paraffin concentrations of 3.2, 5.6 and 10%
    (w/w with respect to digester volatile suspended solids) during the
    first 3-4 days of the experiment, but the gas production recovered
    during the rest of the experiment until termination at day 10.  It
    was concluded in the report that the chlorinated paraffin induced a
    transient partial inhibition and no longer-term effects.

    9.1.2  Aquatic organisms 

         Acute toxicity data for aquatic invertebrates and fish are
    summarized in Table 28.  Chlorinated paraffins of short-chain length
    have been shown to be acutely toxic to both freshwater and saltwater
    invertebrates.  Most of the acute toxicity tests for intermediate
    and long chain chlorinated paraffins on aquatic invertebrates
    exceed the water solubility.  However, a study on intermediate
    chlorinated paraffins suggests that these may be acutely toxic.
    Short, intermediate and long chain chlorinated paraffins appear to
    be of low acute toxicity to fish, the LC50 values being well
    in excess of the water solubility.

    9.1.2.1  Aquatic plants

         Exposure of the freshwater alga  Selenastrum capricornutum for
    10 days to C10-12;58% Cl (CP-SH) at dose levels of 110, 220, 390, 570,
    900 and 1200 µg/litre resulted in a significant inhibition of growth
    at 570 µg/litre.  The calculated EC50 values for cell density over 4,
    7 and 10 days were 3690, 1550 and 1310 µg/litre,  respectively, which
    all exceeded the highest tested concentration (Thompson & Madeley,
    1983d).

         The marine alga  Skeletonema costatum was exposed to C10-12;58%
    Cl (CP-SH) for 10 days at concentrations of 0, 4.5, 6.7, 12.1, 19.6,
    43.1 and 69.8 µg/litre (Thompson & Madeley, 1983b).  Significant
    inhibition of growth was observed on the first 2 days from
    19.6 µg/litre.  The EC50 for cell density after 4 days was
    42.3-55.6 µg/litre, and EC50 for growth rate after 2 days was
    31.6 µg/litre.  No significant reduction in cell density was observed
    after 10 days, indicating an effect on duration of lag phase prior to
    exponential growth or a drop in chlorinated paraffin concentration after
    10 days.

        Table 28.  Acute toxicity of chlorinated paraffins to aquatic organisms

                                                                                                 

    Species               Chlorinated         Parameter        Concentration       Reference
                          paraffin                             (µg/litre)
                                                                                                 

    Water flea            C10-12;58% Cl       48-h EC50b       530                 Thompson &
    Daphnia magna         C10-12;58% Cl       72-h EC50b       24                  Madeley
    (freshwater)          C10-12;58% Cl       96-h EC50b       18                  (1983c)
                          C10-12;58% Cl       120-h EC50b      14
                          C14-17;52% Cl       48-h EC50b       37                  Frank &
                                                                                   Steinhäuser
                                                                                   (in press)

    Mysid shrimp          C10-12;58% Cl       96-h LC50        14.1-15.5           Thompson &
    Mysidopsis bahia                                                               Madeley
    (estuarine)                                                                    (1983a)

    Nitocra spinipes      C10-13;49% Cl       96-h LC50        100                 Tarkpea
    (marine               C10-13;70% Cl       96-h LC50        < 300               et al.
    crustacean)           C14-17;45% Cl       96-h LC50        9000                (1981)
                          C14-17;52% Cl       96-h LC50        > 10 × 106
                          C22-26;42% Cl       96-h LC50        > 1 × 106
                          C22-26;49% Cl       96-h LC50        > 10 × 106

    Bleak                 C10-13;49%,         96-h LC50        > 5 × 106           Lindén et
    Alburnus               63%, 71% Cla                                            al. (1979)
    alburnus              C10-13;56%, Cl      96-h LC50        > 10 × 106
    (estuarine)           C11.5;70% Cl        96-h LC50        > 10 × 106
                          C15.5;40% Cl        96-h LC50        > 5 × 106
                          C14-17;50%,         96-h LC50        > 5 × 106
                           52% Cla
                          C22-26;42% Cl       96-h LC50        > 5 × 106
                          C18-26;49% Cl       96-h LC50        > 5 × 106

    Rainbow trout         C20-30;42% Cl       96-h LC50        770 × 103           Madeley &
    Oncorhynchus                                                                   Birtley
    mykiss                                                                         (1980)
    (freshwater)
                                                                                                 

    a    Consecutive percentage chlorinations refer to different tests
    b    EC50 based on immobilization
    
    9.1.2.2  Invertebrates

         Short-term toxicity data for aquatic invertebrates are summarized
    in Table 29 and chronic toxicity data in Table 30.

         The freshwater crustacean  Daphnia magna was exposed to a short
    chain length paraffin with 58% Cl (CP-SH) (Thompson & Madeley, 1983c). 
    The chlorinated paraffin caused the organisms to float at or near the
    surface of the water at 75 µg/litre or more.  All water fleas died at
    16.3 µg/litre after 6 days in a continuous-flow experiment. The
    following LC50 values were calculated: 3 days, 24 µg/litre; 4 days,
    18 µg/litre; 5 days, 14 µg/litre; 6 to 21 days, 12 µg/litre.  No dead
    parent  Daphnia were observed at 8.9 µg/litre after 21 days of
    exposure, but 37% of the offspring were dead as compared to 6% and 9%
    in the controls. No increased mortality in the offspring was observed
    at 5.0 µg/litre.  The number of offspring per female was reduced at
    2.7 µg/litre.

          Daphnia magna was studied in a 48-h test with C14-17;52% Cl and
    C18-20;52% Cl.  Using the water-soluble fraction of a loading
    concentration of 100 mg/litre, an EC50 of 37 µg/litre for the
    intermediate chain length chlorinated paraffin and an EC0 of
    > 26 µg/litre for the long chain length chlorinated paraffin were
    observed.  In a 21-day reproduction test, daphnids were exposed to the
    water-soluble fraction of both chlorinated paraffins.  With a loading
    of 100 mg/litre, a no-observed-effect concentration of 4.4-8.8 µg/litre
    was found for reproduction rate and parent mortality (LOEC =
    19.9-35.6 µg/litre) for the intermediate chain length chlorinated
    paraffin.  For the long chain length chlorinated paraffin, a LOEC of
    < 1.2 µg/litre was found for the same two parameters.  In these
    studies it was observed that a higher loading concentration of
    10 g/litre caused an increase in the effect concentrations (Frank &
    Steinhäuser, in press).

         In studies of the marine shrimp  Mysidopsis bahia, the 96-h
    LC50 was between 14.1 and 15.5 µg/litre after exposure to a short
    chain length chlorinated paraffin with 58% Cl (CP-SH) (Thompson &
    Madeley, 1983a).  After 28 days of exposure to 0.6, 1.2, 2.4, 3.8 and
    7.3 µg/litre, increased mortality was observed but this was not
    treatment-related.  The increased mortality was significantly
    different from the control (at 1.2 and 2.4 µg/litre) but not from the
    solvent control, and was therefore considered as not related to the
    chlorinated paraffin concentration.  No treatment-related effects of
    this chlorinated paraffin on reproductive rate or growth over this
    time period were observed.

        Table 29.  Short-term toxicity data for aquatic invertebrates

                                                                                                                                      

    Chlorinated paraffin   Organism            LC50            Exposure  Other effects             LOEC          References
                                                               period
                                                                                                                                      

    C10-13;49% Cl (CP-SL)  Nitocra spinipes    100 µg/litre    96 h                                              Tarkpea et al.
                                                                                                                 (1981)

    C10-12;58% Cl (CP-SH)  Dapnia magna        24 µg/litre     3 days    Increased mortality in    8.9 µg/litre  Thompson & Madeley
                                                                         offspring after 21 days                 (1983c)

    C10-12;58% Cl (CP-SH)  Mysidopsis bahia    14.1-15.5       96 h      No effects after 28 days                Thompson & Madeley
                                               µg/litre                  of exposure up to                       (1983a)
                                                                         7.3 µg/litre

    C10-12;58% Cl (CP-SH)  Midge larvae,                       48 h      No adverse effects                      EG & G Bionomics
                           Chironomus tentans                            after exposure to                       (1983)
                                                                         18-162 µg/litre

    C10-13;70% Cl (CP-SH)  Nitocra spinipes    < 300 µg/litre  96 h                                              Tarkpea et al.
                                                                                                                 (1981)

    C14-17;45% Cl (CP-ML)  Nitocra spinipes    9000 µg/litre   96 h                                              Tarkpea et al.
                                                                                                                 (1981)

    C14-17;52% Cl (CP-MH)  Nitocra spinipes    > 10 × 106        96 h                                            Tarkpea et al.
                                               µg/litrea                                                         (1981)
                                                                                                                                      

    Table 29.  (Cont'd)

                                                                                                                                      

    Chlorinated paraffin   Organism            LC50            Exposure  Other effects             LOEC          References
                                                               period
                                                                                                                                      

    C22-26;42% Cl (CP-LL)  Nitocra spinipes    > 1 × 106         96 h                                            Tarkpea et al.
                                               µg/litrea                                                         (1981)

    C22-26;49% Cl (CP-LL)  Nitocra spinipes    > 10 × 106        96 h                                            Tarkpea et al.
                                               µg/litrea                                                         (1981)
                                                                                                                                      

    a    Exceeding the water solubility

    Table 30.  Chronic toxicity of chlorinated paraffins to aquatic invertebrates

                                                                                                                                      

    Chlorinated paraffin     Organism             Exposure     Effect                    Concentration   References
                                                  period                                 (µg/litre)
                                                                                                                                      

    C10-12;58% Cl            Water flea,          6-12 days    LC50                      12              Thompson & Madeley (1983c)
                             Daphnia magna
                                                  21 days      Increased mortality in    8.9
                                                               offspring after 21 days

    C10-12;58% Cl            Mysid shrimp,        28 days      No treatment-related      7.3             Thompson & Madeley (1983a)
                             Mysidopsis bahia                  effects

    C10-12;58% Cl            Midge larvae,        49 days      Halting adult             121             EG & G Bionomics (1983)
                             Chironomus tentans                emergence (100%)

    C10-12;58% Cl            Mussel,              60 days      LC50                      74              Madeley & Thompson (1983a)
                             Mytilus edulis
                                                  84 days      Growth reduction          9.3             Thompson & Shillabeer (1983)
                                                  91 days      23% mortality during      10.1            Madeley et al. (1983a)
                                                               exposure and 10%
                                                               mortality during
                                                               depuration

    C10-12;58% Cl (CP-SH)    Alga, Selenastrum    10 days      Inhibition of growth      570             Thompson & Madeley (1983d)
                             capricornutum

    C10-12;58% Cl (CP-SH)    Alga, Skeletonema    10 days      Inhibition of growth      19.6            Thompson & Madeley (1983b)
                             costatum

    C14-17;52% Cl (CP-MH)    Mussel               60 days      Decreased filtration      3800            Madeley & Thompson (1983b)
                             Mytilus edulis                    activity
                                                                                                                                      

    Table 30.  (Cont'd)

                                                                                                                                      

    Chlorinated paraffin     Organism             Exposure     Effect                    Concentration   References
                                                  period                                 (µg/litre)
                                                                                                                                      

    C14-17;52% Cl            Water flea,          21 days      Reproduction & parent     19.9-35.6       Frank & Steinhäuser (1994)
                             Daphnia magna                     mortality (LOEC)

    C18-20;52% Cl            Water flea,          21 days      Reproduction & parent     < 1.2           Frank & Steinhäuser (1994)
                             Daphnia magna                     mortality (LOEC)

    C22-26;43% Cl (CP-LL)    Mussel,              60 days      Decreased filtration      2.180           Madeley & Thompson (1983c)
                             Mytilus edulis                    activity

    C20-30;70% Cl (CP-LH)    Mussel,              60 days      Decreased filtration      1330            Madeley & Thompson (1983d)
                             Mytilus edulis                    activity
                                                                                                                                      
             Larvae of the midge  Chironomus tentans (second instar) were
    exposed to C10-12;58% Cl (CP-SH) concentrations from 18 to 162 µg/litre
    for 48 h (EG & G Bionomics, 1983).  No adverse effects could be
    detected.  Exposure to 61-394 µg/litre for the 49 days life cycle
    gave no effects except for halting adult emergence (100%) at 121 and
    394 µg/litre.

         The mussel  Mytilus edulis was exposed to 2.3 and 10.1 µg/litre
    of C10-12;58% Cl (CP-SH) for 147 days followed by 98 days of
    depuration (2.3 µg/litre) or 91 days followed by 84 days depuration
    (10.1 µg/litre) (Madeley et al. 1983a).  A third of the mussels in the
    high-dose group died during the exposure (23%) or depuration periods
    (10%), and 7% of those in the low dose group, but this did not differ
    significantly from the number of deaths in the acetone control.

         When the mussel  Mytilus edulis was studied over 60 days after
    exposure to 13, 44, 71, 130 and 930 µg/litre of C10-12;58% Cl (CP-SH),
    there was significant mortality at the three highest dose levels, the
    median lethal time (LT50) values being 59.3, 39.7 or 26.7 days,
    respectively (Madeley & Thompson, 1983a). The highest dose exceeded
    the maximal solubility of the chlorinated paraffin.  The LC50 for
    this 60-day period was 74 µg/litre.

         Mussels  (Mytilus edulis) were exposed to 2.3 and 9.3 µg/litre
    of a short chain length paraffin (58% Cl) (CP-SH) in sea water for 12
    weeks (Thompson & Shillabeer, 1983).  There were no mortalities at
    either concentration, but at 9.3 µg/litre a reduction in growth rate
    was observed, measured as shell length and tissue weight.

         Treatment of mussels  (Mytilus edulis) for 60 days with
    C14-17;52% Cl (CP-MH) at concentration of 220 and 3800 µg/litre
    gave no significant mortality, but there was an observed decrease
    (non-quantitative visual observation) in filtration activity at the
    higher concentration (Madeley & Thompson, 1983b).  The highest dose
    exceeded the maximal water solubility of the chlorinated paraffin.

         Treatment of mussels  (Mytilus edulis) with C22-26;43% Cl (CP-LL)
    at 120 or 2180 µg/litre or with C20-30;70% Cl (CP-LH) at 460 and
    1330 µg/litre for 60 days did not cause mortality, but visual
    observation suggested that the filtration activity was reduced at the
    higher dose levels (Madeley & Thompson, 1983c,d).  The highest doses
    exceeded the maximal solubility of the chlorinated paraffins.

    9.1.2.3  Fish

         Acute toxicity data are shown in Table 28 and chronic toxicity
    data for fish are summarized in Table 31.

        Table 31.  Chronic toxicity of chlorinated paraffins to fish

                                                                                                                                      

    Chlorinated paraffin   Organism                Exposure   Effect                      Concentration    References
                                                   period                                 (µg/litre)
                                                                                                                                      

    C10-13;49%, 59%,       Bleak,                  14 days    Behavioural effects         125 (single      Bengtsson & Baumann Ofstad
    71% Cl                 Alburnus alburnus                                              concentration)   (1982)

    C10-12;58% Cl          Sheepshead minnow,      32 days    Significantly reduced       279.7            Hill & Maddock (1983)
                           Cyprinodon variegatus              size of larvae (LOEC)

    C10-12;58% Cl          Rainbow trout           60 days    LC50                        340              Madeley & Maddock (1983c)
                           Oncorhynchus mykiss
                                                   60 days    Behavioural abnormalities   33

                                                   168 days   after 60-70 days of                          Madeley & Maddock (1983b)
                                                              depuration

                                                              50% mortality               3.1

                                                              100% mortality              14.3

    C14-17;50% Cl          Bleak,                  14 days    No observed effect          125 (single      Bengtsson et al. (1979)
                           Alburnus alburnus                                              concentration)

    C14-17;52% Cl          Rainbow trout,          60 days    No observed effect          1050             Madeley & Maddock (1983c)
                           Oncorhynchus mykiss

    C18-26;49% Cl          Bleak,                  14 days    No observed effect          125 (single      Bengtsson et al. (1979)
                           Alburnus alburnus                                              concentration)

    C20-30;43%, 70% Cl     Rainbow trout,          60 days    No observed effect          3800             Madeley & Maddock (1983c)
                           Oncorhynchus mykiss
                                                                                                                                      
             In a 96-h study on rainbow trout  (Oncorhynchus mykiss), no
    toxic effects or effects on behaviour were observed after exposure
    of the fish to an emulsion containing a mean concentration of
    770 000 µg/litre of Cereclor 42 (C20-30;42% Cl, CP-LL) (Madeley
    & Birtley, 1980).

         In bleak  (Alburnus alburnus) which were exposed to Witaclor 149
    (C10-13;49% Cl, CP-SL), Witaclor 159 (C10-13;59% Cl, CP-SH) and Witaclor
    171P (C10-13;71% Cl, CP-SH) (125 µg/litre of water) for 14 days, some
    effects on behaviour, such as sluggish movements, absence of shoaling
    behaviour and abnormal vertical postures were observed after 7 days
    (Bengtsson et al., 1979).  The effects disappeared after the fish had
    been kept in clean water for 2 days.  No effects on behaviour were
    observed after exposure to chlorinated paraffins with intermediate or
    long chain length chlorinated paraffins, Witaclor 350 (C14-17;50% Cl,
    CP-MH) or Witaclor 549 (C18-26;49% Cl, CP-LL), suggesting that
    behavioural toxicity is related to the carbon chain length of the
    chlorinated paraffin.  When bleak were given food contaminated with
    590, 2500 or 5800 mg/kg Witaclor 149 or 3180 mg/kg Witaclor 171P for
    91 days, effects on behaviour were noted (Bengtsson & Baumann Ofstad,
    1982).  After 5 weeks of exposure to the high dose of Witaclor 149,
    after 7 weeks of exposure to the medium dose and after 12 weeks of
    exposure to Witaclor 171P, the fish swam sluggishly and closer to the
    bottom than usual.  In addition, folded dorsal fins and minor balance
    problems were observed.  These effects gradually disappeared within 2
    weeks after exposure finished.

         Flounders  (Platichthys flesus) of both sexes were fed Witachlor
    149 (C12;49% Cl, CP-SL) or Chlorparaffin Hüls 70C (C12;70% Cl, CP-SH)
    on days 1 and 4 with a total exposure of 1000 mg/kg body weight (Haux
    et al., 1982).  The experiment was performed in both brackish and
    seawater.  The fish were examined 13 and 27 days after the first
    administration.  The male flounders did not appear to be affected by
    the two chlorinated paraffins.  C12;70% Cl did not induce any
    haematological responses, whereas C12;49% Cl seemed to affect the
    erythrocyte balance of female fish.  C12;49% Cl resulted in
    hypoglycaemia in marine female fish, whereas C12;70% Cl caused
    hyperglycaemia in female brackish water fish.  In females exposed to
    C12;49% Cl, a significant increase in benzo [a]pyrene hydroxylase
    activity was observed after 27 days in brackish water.  A decrease in
    6ß-hydroxylase activity in marine female fish and an increase in 5
    alpha,ß-reductase activity in brackish water female fish were induced
    by C12;70% Cl after 13 days.

         The hatchability of embryos and survival of larvae of the
    sheepshead minnow  (Cyprinodon variegatus) was unaffected by a 28-day
    exposure to short chain length paraffin with 58% Cl (CP-SH) (2.4, 4.1,
    6.4, 22.1 and 54.8 µg/litre (Hill & Maddock, 1983).  The treated
    minnows showed an increased larval growth compared to the acetone
    control.  When the larvae were exposed to 36.2, 71, 161.8, 279.7 and

    620.5 µg/litre for 32 days they were significantly smaller in the two
    highest exposure groups, but in the lower exposure groups (36.2 and
    71 µg/litre) they were significantly larger than the controls.  No
    effect was seen on survival of larvae and hatchability of embryos.

         In a study by Madeley & Maddock (1983c) four chlorinated paraffins
    were examined for their toxicity to rainbow trout  (Oncorhynchus mykiss)
    after exposure for 60 days.  C10-12;58% Cl was used at mean
    concentration of 33, 100, 350, 1070 and 3050 µg/litre. Significant
    mortality was observed with the highest three concentrations.  LT50
    values (mean lethal times) for these three concentrations were
    calculated as 44.7, 31.0 and 30.4 days, respectively.  The calculated
    60-day LC50 was 340 µg/litre.  Behavioural abnormalities, which
    were dose-related, were also observed.

         Rainbow trout  (Oncorhynchus mykiss) were exposed to 3.1 and
    14.3 µg/litre of C10-12;58% Cl (CP-SH) for 168 days followed by a
    depuration period of up to 105 days.  No deaths occurred during the
    exposure period, but during days 63 to 70 of the depuration period
    all of the trout exposed to 14.3 µg/litre died and there was a
    significantly increased mortality (50%) among those exposed to
    3.1 µg/litre (Madeley & Maddock, 1983b).  The relationship to
    chlorinated paraffin exposure is unknown, since the surviving fish
    recovered after day 70.

         Rainbow trout  (Oncorhynchus mykiss) were exposed to a short
    chain length paraffin (58% Cl) (CP-SH) for 168 days (Madeley &
    Maddock, 1983a) at 3.4 and 17.2 µg/litre.  The treatment did not cause
    any significant mortality or differences in growth, but small changes
    in behaviour such as increased food intake were observed (compared to
    controls).

         Madeley & Maddock (1983c) exposed rainbow trout  (Oncorhynchus
     mykiss) to 4500 and 1050 µg/litre of a chlorinated paraffin (C14-17;
    52% Cl, CP-MH) for 60 days.  No toxic effects were found.

         In other studies rainbow trout  (Oncorhynchus mykiss) were
    exposed to C22-26;43% Cl (CP-LL) for 60 days at concentrations of 900
    and 4000 µg/litre (Madeley & Maddock, 1983c) or to C20-30;70% Cl
    (CP-LH) at 3800, 1900 and 840 µg/litre (Madely & Maddock, 1983d).  No
    toxic effects were found.

    9.1.3  Terrestrial organisms

         A one-generation reproduction study was performed with Chlorowax
    500C (C10-13;58% Cl, CP-SH) on mallard ducks  (Anas platyrhynchos)
    (Shults et al., 1984).  The ducks were fed 0, 28, 166 and 1000 mg/kg
    diet for 22 weeks in groups of 20 pairs.  During the treatment the

    ducks were mated.  The treatment had no effect on the survival,
    physical condition, body weight or food  consumption of the adult
    ducks.  Decreased egg-shell thickness and a 10% loss of 14-day embryo
    viability were observed in the highest exposure group.

         The acute toxicity of orally administered Cereclor S52 (C14-17;52%
    Cl, CP-MH) was studied in ring-necked pheasants  (Phasianus
     colchicus) and mallard ducks  (Anas platyrhynchos) (Madeley &
    Birtley, 1980).  However, no abnormal clinical signs, mortality or
    effects on body weight gain were observed 14 days after a single oral
    dose by gavage of up to 24 606 mg/kg body weight (pheasant) and
    10 280 mg/kg body weight (duck) (five male and five female birds per
    group).  When the birds were fed with 1000 or 24 063 mg/kg diet of
    Cereclor S52 for 5 days followed by 3 days on normal food (five males 
    and five females per group), no abnormalities were found other than
    inferior food intake in ducks from the high-dose group.

         The toxicity of Cereclor 42 (C22-26;42% Cl, CP-LL), Cereclor 50LV
    (C10-13;49% Cl, CP-SL) and Cereclor 70L (C10-13;70% Cl, CP-SH) in chick
    embryos was studied by Brunström (1983).  The chlorinated paraffins
    were injected into the yolks of eggs incubated for 4 days at
    concentrations of 100 and 200 mg/kg egg (based on mean egg weights
    before incubation).  None of the three mixtures affected the hatching
    rate, incubation time, hatching weight, weight gain after hatching or
    the liver weights of the chicks.

         In an extension of this study the eggs were injected with
    300 mg/kg egg weight of the same Cereclors after 4 days of incubation
    (Brunström, 1985).  An increased liver weight was observed after
    treatment with C10-13;49% Cl and C10-13;70% Cl.  The microsomal
    concentration of cytochrome P-450 in chick embryos was increased by
    all three Cereclors.  The highest concentration was observed with
    C10-13;70% Cl.  This Cereclor was also found to increase the microsomal
    activity of APMD.  The other short-chain chlorinated paraffin,
    C10-13;49% Cl, produced decreased activities of aryl hydrocarbon
    hydroxylase (AHH) and 7-ethoxycoumarin  O-deethylase (ECOD).  The
    long chain length chlorinated paraffin in this study, C22-26;42% Cl,
    caused decreased activities of APDM and ECOD.  The greatest effects
    were observed after treatment with the most highly chlorinated
    short-chain paraffin, C10-13;70% Cl.

    9.2  Field observations

         No data concerning the effects of chlorinated paraffins in the
    field have been reported.

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

    10.1  Evaluation of human health risks

    10.1.1  Exposure levels

         Information on occupational exposure to chlorinated paraffins is
    very limited.  The principal route of exposure is likely to be dermal,
    particularly during their use as metal-working fluids.  There is also
    potential for the formation of inhalable aerosols during this use,
    though available information is inadequate to assess exposure via this
    route.

         Owing to the high octanol-water partition coefficient, it is
    likely that the principal source of exposure of the general population
    is food, although, owing to lack of data, exposure via other routes
    cannot be ruled out.  It should be noted, however, that the
    composition of chlorinated paraffins to which the population is
    exposed in the general environment may be considerably different from
    that of the commercial products, although it is not possible currently
    to distinguish the chemical composition of chlorinated paraffins with
    available methods of analysis.  In the only survey of foodstuffs
    identified, which was limited in scope, the highest concentration of
    chlorinated paraffins (average level of C10-20: 300 µg/kg) was present
    in dairy products (Table 15).  If the daily consumption of dairy
    products is assumed to be 1 kg per person, the daily intake of short
    and intermediate chain length chlorinated paraffins from this source
    would be 300 µg (4.3 µg/kg body weight, assuming an average body
    weight of 70 kg).  This is likely to be a worst-case estimate based on
    the lack of specificity of the analytical method.

         Exposure to chlorinated paraffins via food is also possible
    through the consumption of contaminated mussels.  Assuming a weekly
    consumption of 1 kg of mussels, as a worst case, this would correspond
    to a weekly intake of short and intermediate chain length chlorinated
    paraffins of 3250 µg, based on chlorinated paraffin levels found in
    mussels collected at various sites in the United Kingdom (Table 13)
    (6.7 µg/kg body weight per day, assuming an average body weight of
    70 kg).  If the mussels are collected in highly contaminated water
    (section 5.1.4) the weekly intake would be 12 000 µg, which
    corresponds to 25 µg/kg body weight per day.  The analytical method
    used was non-specific.

    10.1.2  Toxic effects

         In spite of the widespread use of the chlorinated paraffins,
    there have been no case reports of skin irritation or sensitization
    in humans. Results from a limited number of studies on volunteers
    show that chlorinated paraffins can induce minimal irritancy in
    the skin but not sensitization.  No other data concerning effects of
    chlorinated paraffins on humans have been reported.

         The acute oral toxicity of chlorinated paraffins of various chain
    lengths has been well studied in experimental animals and is low. 
    Toxic effects such as muscular incoordination and piloerection
    were most evident following single exposure to short chain length
    chlorinated paraffins.  On the basis of very limited data, the acute
    toxicity by the inhalation and dermal routes also appears to be low.
    Mild skin and eye irritation have been observed after application of
    short and intermediate (skin irritation) chain length chlorinated
    paraffins.  Results of several studies indicate that short chain
    chlorinated paraffins do not induce skin sensitization.

         In repeated dose toxicity studies by the oral route, the liver,
    kidney and thyroid have been shown to be the primary target organs for
    the toxicity of chlorinated paraffins (Table 32).  For the short chain
    compounds, increases in liver and kidney weight and hypertrophy of the
    liver and thyroid have been observed at lowest doses (LOEL = 100 mg/kg
    body weight per day; NOEL = 10 mg/kg body weight per day; rats).

         For the intermediate chain compounds, effects observed at lowest
    doses are generally increases in liver and kidney weight (LOEL in rats
    = 100 mg/kg body weight per day, respectively; NOAEL in rats =
    10 mg/kg body weight per day).  Increases in serum cholesterol and
    "mild, adaptive" histological changes in the thyroid have been reported
    at similar doses in female rats (NOAEL = 4 mg/kg body weight per day).

         For the long chain compounds, effects observed at lowest doses
    are multifocal granulomatous hepatitis and increased liver weight in
    female rats (LOAEL = 100 mg/kg body weight per day).

         Chlorinated paraffins do not appear to induce mutations in
    bacteria.  However, in mammalian cells, there is a suggestion of a
    weak  in vitro clastogenic potential but not in several  in vivo
    studies.  Chlorinated paraffins are also reported to induce  in vitro
    cell transformation.

        Table 32.  Effect levels (non-carcinogenic) in repeated dose toxicity tests

                                                                                                 

    Short chain length chlorinated paraffins

    Rats

    C10-13;58% Cl, 14-day dietary study in Fischer-344 rats,
    LOEL = 100 mg/kg body weight per day (increase in relative liver weights and activities of
    hepatic APDM and cytochrome P-450)

    C10-13;58% Cl, 14-day gavage study in Fischer-344 rats,
    LOEL = 100 mg/kg body weight per day (increase in relative liver weights);
    NOEL = 30 mg/kg body weight per day

    C10-13;58% Cl, 14-day gavage study in Alpk:APfSD rats,
    LOEL = 100 mg/kg body weight per day (increase in liver/body weight ratio);
    NOEL = 50 mg/kg body weight per day

    C10-13;56% Cl, 14-day gavage study in Alpk:APfSD rats,
    LOEL = 50 mg/kg body weight per day (increase in liver/body weight ratio);
    NOEL = 10 mg/kg body weight per day

    C12;58% Cl, 90-day gavage study in Fischer-344 rats
    LOEL = 313 mg/kg body weight per day (increase in relative liver weight, hepatic
    peroxisomal ß-oxidation and thyroxine-UdPG-glucuronosyltransferase; thyroid follicular
    cell hypertrophy and hyperplasia and increase in replicative DNA synthesis; renal tubular
    eosinophilia and increase in renal replicative DNA synthesis)
    No effects in Dunkin Hartley guinea-pigs
    NOEL = 1000 mg/kg body weight per day

    C10-13;58% Cl, 13-week gavage study in Fischer-344 rats,
    LOEL = 100 mg/kg body weight per day (increase in liver and kidney weights and hypertrophy
    of liver and thyroid);
    NOEL = 10 mg/kg body weight per day

    C12;60% Cl, 90-day gavage study in Fischer-344 rats,
    LOEL = 313 mg/kg body weight per day (increase in liver weight)

    C12;60% Cl, 2-year gavage study in Fischer-344 rats,
    LOAEL = 312 mg/kg body weight per day (increase in liver and kidney weights, hepatic
    hypertrophy, necrosis and angiectasis, nephropathy (females), erosion, inflammation and
    ulceration of the glandular stomach, hyperplasia of the parathyroid)
                                                                                                 

    Table 32.  (Cont'd)

                                                                                                 

    Short chain length chlorinated paraffins (cont'd)

    Mice

    C10-13;58% Cl, 14-day gavage study in Alpk:APfCD mice,
    LOEL = 250 mg/kg body weight per day (induction of peroxisomal fatty acid ß-oxidation and
    increase in liver weight);
    NOEL = 100 mg/kg body weight per day

    C10-13;56% Cl, 14-day gavage study in Alpk:APfCD mice
    LOEL = 100 mg/kg body weight per day (increase in liver weight);
    NOEL = 50 mg/kg body weight per day

    C12;60% Cl, 90-day gavage study in B6C3F1 mice,
    LOEL  = 250 mg/kg body weight per day (hepatocellular hypertrophy);
    NOEL = 125 mg/kg body weight per day

    C12;60% Cl, 2-year day gavage study in B6C3F1 mice,
    LOEL  = 125 mg/kg body weight per day (decrease in body weight gain (females))

    Intermediate chain length chlorinated paraffins

    Rats

    C14-17;52% Cl, 14-day dietary study in Fischer-344 rats,
    LOEL = 177 mg/kg body weight per day (slight increase in cytochrome P-450);
    NOEL = 57.7 mg/kg body weight per day

    C14-17;40% Cl, 14-day gavage study in Alpk:APfSD rats,
    LOEL = 10 mg/kg body weight per day (increase in liver weight; not dose-related)

    C14-17;52% Cl, 13-week study in Sprague-Dawley rats,
    NOAEL (females) = 4.2 mg/kg body weight per day (increase in serum cholesterol; "mild,
    adaptive" histopathological changes in the thyroid - reduced follicle sizes and collapsed
    angularity; increased height, cytoplasmic vacuolation and nuclear vesiculation);
    NOEL = 0.4 mg/kg body weight per day

    C14-17;52% Cl, 90-day dietary study in Wistar rats,
    LOEL (females) = 25 mg/kg body weight per day (increases in liver and kidney weights and
    proliferation of smooth endoplastic reticulum);
    NOEL = 12.5 mg/kg body weight per day

    C14-17;52% Cl, 90-day dietary study in Fischer-344 rats,
    LOEL = 100 mg/kg body weight per day (increased liver and kidney weights);
    NOEL = 10 mg/kg body weight per day
                                                                                                 

    Table 32.  (Cont'd)

                                                                                                 

    Intermediate chain length chlorinated paraffins (cont'd)

    Mice

    C14-17;40% Cl, 14-day gavage study in Alpk:APfCD-1 mice,
    LOEL = 500 mg/kg body weight (induction of peroxisomal fatty acid ß-oxidation);
    NOEL = 250 mg/kg body weight per day

    Dogs

    C14-17;52% Cl, 90-day dietary study in Beagle dogs,
    LOEL (males) = 30 mg/kg body weight per day (increased liver and kidney weights)
    NOEL = 10 mg/kg body weight per day (increased smooth endoplasmic reticulum)

    Long chain length chlorinated paraffins

    Rats

    C22-26;70% Cl, 14-day dietary study in Fischer-344 rats,
    NOEL = 1715 mg/kg body weight per day (no effects at any dose level)

    C22-26;43% Cl, 14-day dietary study in Charles River rats,
    NOEL = 3000 mg/kg body weight per day (no effects at any dose; observation of
    nephrolithiasis in females exposed to 3000 mg/kg body weight per day)

    C23;43% Cl, 90-day gavage study in Fischer-344 rats,
    LOAEL (females) = 235 mg/kg body weight per day (granulomatous inflammation in the liver)

    C20-30;43% Cl, 90-day gavage study in Fischer-344 rats,
    LOAEL (females) = 100 mg/kg body weight per day (multifocal granulomatous hepatitis and
    increased liver weight)

    C22-26;70% CL, 90-day dietary study in Fischer-344 rats,
    LOAEL = 3750 mg/kg body weight per day (increased liver weight, hepatocellular hypertrophy
    and cytoplasmic fat vacuolation; slight increase of chronic nephritis (males); increase in
    ALT and AST (females));
    NOEL = 900 mg/kg body weight per day

    C23;43% Cl, 90-day gavage study in Fischer-344 rats,
    LOAEL = 100 mg/kg body weight per day (increase in relative liver weights; increased
    activities of serum enzymes, variations in haematological parameters (in females); diffuse
    lymphohistiocytic inflammation in the livers, pancreatic and mesenteric lymph nodes)
                                                                                                 

    Table 32.  (Cont'd)

                                                                                                 

    Long chain length chlorinated paraffins (cont'd)

    Mice

    C23;43% Cl, 90-day gavage,
    NOEL = 7500 mg/kg body weight per day (no effects at any dose)

    C23;43% Cl, 90-day gavage,
    NOEL = 5000 mg/kg body weight per day (no effects at any dose)

                                                                                                 
             Two-year toxicity and carcinogenicity studies have been conducted
    for a short (C12;60% Cl) and a long chain chlorinated paraffin
    (C23;43% Cl) in both rats and mice.  For the short chain chlorinated
    paraffin, the incidences of liver and thyroid tumours were increased
    in mice at 125 and 250 mg/kg body weight per day.  In rats, the
    incidences of liver tumours in both sexes, thyroid tumours in females
    and renal cell tumours and leukaemias in males were increased at doses
    of 312 and 625 mg/kg body weight per day.  For the long chain
    chlorinated paraffin, the incidences of malignant lymphomas in male
    mice (2500-5000 mg/kg body weight per day) and phaeochromocytomas in
    female rats (900 mg/kg body weight per day) were increased.  On the
    basis of available data, therefore, the short chain chlorinated
    paraffin was carcinogenic in rats and mice.  No data are available on
    intermediate chlorinated paraffins.  For the long chain chlorinated
    paraffin, the evidence of carcinogenicity is limited, increased
    incidences of commonly occurring tumours having been observed at only
    one site in one sex of each species.

         Some possible mechanisms for the induction of tumours of the
    thyroid, liver and kidney have been suggested.  On the basis of 14-day
    mouse, rat and guinea-pig studies (Wyatt et al., 1993; Elcombe et al.,
    in press), with similar short chain and long chain chlorinated
    paraffins as used in the carcinogenesis bioassays, it was suggested
    that the liver tumours in mice and rats could be correlated with the
    degree of peroxisomal proliferation which occurs in the liver of these
    species at similar dose levels (250 mg/kg body weight per day).  No
    peroxisome proliferation was observed in the livers of guinea-pigs
    even at doses up to 1 to 2 g/kg body weight per day, although a
    similar increase in liver weight to that seen in mice and rats was
    observed.  No study on peroxisome proliferation in human hepatoctyes
    treated with a short chain chlorinated paraffin is available.

         Increased DNA synthesis has been demonstrated in hepatocytes and
    thyroid follicular cells in rats of both sexes and in proximal kidney
    tubular cells in males.  Perturbation of thyroid homeostasis and
    increased TSH secretion has been observed in the thyroid of rats. 
    These effects may be related to the development of tumours.

         Taking into consideration the available data, it appears that
    chlorinated paraffins do not mediate carcinogenic effects via direct
    interaction with DNA.

         In a reproduction study, no adverse reproductive effects were
    reported following exposure of rats to an intermediate chain length
    chlorinated paraffin with 52% chlorine. However, survival and body
    weight of the exposed pups were reduced (LOEL for non-significant
    decrease in body weight = 5.7 to 7.2 mg/kg body weight per day; LOAEL
    for decreased survival = 58.7 to 70 mg/kg body weight per day).  In a
    limited number of studies on the developmental effects of the short,
    medium and long chain chlorinated paraffins, adverse effects in
    offspring were observed, for the short chain compounds only, at
    maternally toxic doses in rats.

    10.1.3  Risk evaluation

         Available data indicate that absorption of chlorinated paraffins
    through the skin (the likely principal route of exposure in the
    occupational environment) is minimal.  Provided that proper personal
    hygiene and safety procedures are followed, the risk to the health of
    workers exposed to chlorinated paraffins is expected to be minimal.

    10.1.3.1  Short chain compounds

         On the basis of available data on repeated dose toxicity, a
    Tolerable Daily Intake (TDI) for non-neoplastic effects of short chain
    chlorinated paraffins for the general population can be developed:

              10 mg/kg body
              weight per day
    TDI =                       =    100 µg/kg body weight per day
                   100

    where 10 mg/kg body weight per day is the lowest reported
    no-observed-effect level (increases in liver and kidney weights
    and hypertrophy of the liver and thyroid at the next highest dose
    in a 13-week study on rats) (IRDC, 1984a); and 100 is the
    uncertainty factor (× 10 for interspecies variation; × 10 for
    intraspecies variation).

         On the basis of multistage modelling of the tumours with highest
    incidence (hepatocellular adenomas or carcinomas (combined) in male
    mice) in the carcinogenesis bioassay with short chain chlorinated
    paraffins, the estimated dose associated with a 5% increase in tumour

    incidence is 11 mg/kg body weight per day (amortized for period of
    administration).  After dividing this value by 1000 (uncertainty
    factor for a non-genotoxic carcinogen), it can be recommended that
    daily doses of short chain chlorinated paraffins for the general
    population should not exceed 11 µg/kg body weight, on the basis of
    neoplastic effects.

    10.1.3.2  Intermediate chain compounds

         On the basis of available data on repeated dose toxicity, a TDI
    for non-neoplastic effects of intermediate chain chlorinated paraffins
    can be developed:

              10 mg/kg body
              weight per day
    TDI =                      =   100 µg/kg body weight per day
                   100

    where 10 mg/kg body weight per day is the no-observed-adverse-effect
    level in both sexes (increases in liver and kidney weights at the next
    highest dose) (IRDC, 1984b); increases in serum cholesterol and "mild,
    adaptive" histological changes in the thyroid have been reported at
    similar doses in female rats (NOAEL = 4 mg/kg body weight per day)
    (Poon et al., in press); and 100 is the uncertainty factor (× 10 for
    interspecies variation; × 10 for intraspecies variation).

    10.1.3.3  Long chain compounds

         On the basis of available data on repeated dose toxicity, a TDI
    for non-neoplastic effects of long chain chlorinated paraffins can be
    developed:

              100 mg/kg body
              weight per day
    TDI =                       =    100 µg/kg body weight per day
                   1000

    where 100 mg/kg = the lowest-observed-adverse-effect levels in
    long-term studies (effects at this dose were multifocal granulomatous
    hepatitis and increased liver weight in female rats (NTP, 1986b;
    Serrone et al., 1987; Bucher et al., 1987); and 1000 = uncertainty
    factor (× 10 for intraspecies variation, × 10 for interspecies
    variation, × 10 for LOAEL rather than NOEL).

         In general, the calculated daily intake of chlorinated paraffins
    based on highly unlikely worst-case scenarios are below the TDIs for
    non-neoplastic effects or recommended values for neoplastic effects
    (short chain compounds) developed above.

    10.2  Evaluation of effects on the environment

    10.2.1  Exposure levels

         Data on chlorinated paraffin levels in the environment are
    limited, but the studies reported indicate widespread contamination,
    although the highest levels are found close to industries that
    manufacture or use chlorinated paraffins.

         Chlorinated paraffins bioaccumulate in aquatic organisms, and
    bioconcentration factors (BCFs) in the range of 7 to 7155 for fish and
    223 to 138 000 for mussels have been reported.  In fish, chlorinated
    paraffins of short chain length are accumulated to a higher degree
    than those of intermediate and long chain length.

         In the environment, chlorinated paraffins are persistent. 
    However, short-chain chlorinated paraffins with a low chlorine content
    appear to be degraded by acclimated microorganisms.

    10.2.2  Toxic effects

         Short chain length chlorinated paraffins are acutely toxic to
    freshwater and saltwater invertebrates at LC/EC50 concentrations
    ranging from 14 to 530 µg/litre.  The acute toxicity of short chain
    chlorinated paraffins to fish is low.  In long-term studies, the
    lowest-observed-effect concentrations for algae, daphnids and fish
    ranged from 3 to 20 µg/litre; NOECs appear to range from 2 to
    5 µg/litre for the most sensitive species tested.  The acute and
    long-term toxicity of intermediate and long chain length chlorinated
    paraffins to fish appears to be low.  However, in daphnids, chronic
    effects of an intermediate and a long-chain product have been observed
    at similar concentrations to those reported for short chain compounds.

         No studies on plants or terrestrial invertebrates have been
    reported.  The acute toxicity to birds is low.  Data from studies on
    laboratory mammals suggest a low risk for terrestrial mammals.

    10.2.3  Risk evaluation

         The evaluation of the environmental risks of chlorinated
    paraffins is complicated by the limited quality and quantity of
    information regarding environmental levels.  Available data indicate
    that chlorinated paraffins are bioaccumulative and persistent.

         The data on environmental levels of short-chain chlorinated
    paraffins indicate that in areas local to release sources, there is a
    risk to both freshwater and estuarine organisms.  Recent data indicate
    that there is also a potential risk to aquatic invertebrates from
    intermediate and long chain chlorinated paraffin products.

         The enrichment of chlorinated paraffins in sediments, their
    resorption behaviour and aquatic toxicity indicate a potential risk
    for sediment-dwelling organisms.

         The data regarding chlorinated paraffins in the terrestrial
    environment are insufficient to estimate the risk to soil-dwelling
    organisms.

    11.  RECOMMENDATIONS FOR PROTECTION OF THE ENVIRONMENT

         Since chlorinated paraffins are bioaccumulative and toxic to
    environmental organisms and owing to difficulties in monitoring
    environmental levels, it is recommended that use and disposal of these
    compounds should be controlled to avoid release to the environment.

    12.  FUTURE RESEARCH

         The following studies need to be undertaken:

    a)   development of more selective and sensitive methods of analysis
         in order to provide more reliable data on present and future
         levels of chlorinated paraffins in the occupational environment,
         soil, water, sediments, foodstuffs and human tissues;

    b)   further investigation of the influence of the chain lengths and
         degrees of chlorination on toxicodynamics and toxicokinetics of
         chlorinated paraffins, with particular regard to the relative
         extent and rate of absorption and excretion through different
         routes; studies to ascertain the metabolic pathways of
         chlorinated paraffins should also be performed;

    c)   investigation of the toxicokinetics and half-lives of chlorinated
         paraffins in mammals;

    d)   studies on perinatal toxicity;

    e)   further studies to examine effects on sediment-dwelling
         organisms.

    13.  PREVIOUS EVALUATION BY INTERNATIONAL ORGANIZATIONS

         Chlorinated paraffins have been evaluated by the International
    Agency for Research on Cancer (IARC, 1990).  It was concluded that
    there is sufficient evidence for the carcinogenicity of a commercial
    chlorinated paraffin product of average carbon chain length C12 and
    average degree of chlorination of 60% in experimental animals, and
    limited evidence for the carcinogenicity of a commercial chlorinated
    paraffin product of average carbon chain length C23 and average
    degree of chlorination of 43% in experimental animals.  The overall
    evaluation was that chlorinated paraffins of average carbon chain
    length C12 and average degree of chlorination of approximately 60%
    are possibly carcinogenic to humans (Group 2B).

    REFERENCES

    Åhlman M, Bergman Å, Darnerud PO, Egestad B, & Sjövall J (1986)
    Chlorinated paraffins: formation of sulphur-containing metabolites of
    polychlorohexadecane in rats. Xenobiotica, 16: 225-232.

    Ahotupa M, Hietanen E, Mantyla E, & Vainio H (1982) Effects of
    polychlorinated paraffins on hepatic, renal and intestinal
    biotransformation rates in comparison to the effects of poly-
    chlorinated biphenyls and naphthalenes. J Appl Toxicol, 2: 47-53.

    Anderson BE, Zeiger E, Shelby MD, Resnick MA, Gulati DK, Ivett JL, &
    Loveday KS (1990) Chromosome aberration and sister chromatid exchange
    test results with 42 chemicals. Environ Mol Mutagen, 16(Suppl 18):
    55-137.

    Ashby J, Lefevre PA, & Elcombe CR (1990) Cell replication and
    unscheduled DNA synthesis (UDS) activity of low molecular weight
    chlorinated paraffins in the rat liver  in vivo. Mutagenesis,
    5: 515-518.

    Bengtsson BE & Baumann Ofstad E (1982) Long-term studies on uptake and
    elimination of some chlorinated paraffins in the bleak,  Alburnus
     alburnus. Ambio, 11: 38-40.

    Bengtsson BE, Svanberg O, Lindén E, Lunde G, & Baumann Ofstad E (1979)
    Structure related uptake of chlorinated paraffins in bleaks ( Alburnus
     alburnus L). Ambio, 8: 121-122.

    Bergman Å, Hagman A, Jacobsson S, Jansson B, & Åhlman M (1984) Thermal
    degradation of polychlorinated alkanes. Chemosphere, 13: 237-250.

    Biessmann A, Brandt I, & Darnerud PO (1982) Comparative distribution
    and metabolism of two carbon-14 labeled chlorinated paraffins in
    Japanese quail  (Coturnix coturnix japonica). Environ Pollut,
    A28: 109-120.

    Biessmann A, Darnerud PO, & Brandt I (1983) Chlorinated paraffins:
    disposition of a highly chlorinated polychlorohexadecane in mice and
    quail. Arch Toxicol, 53: 79-86.

    Birtley RDN, Conning DM, Daniel JW, Ferguson DM, Longstaff E, & Swan
    AAB (1980) The toxicological effects of chlorinated paraffins in
    mammals. Toxicol Appl Pharmacol, 54: 514-525.

    Brunström B (1983) Toxicity in chick embryos of three commercial
    mixtures of chlorinated paraffins and of toxaphene injected into eggs.
    Arch Toxicol, 54: 353-357.

    Brunström B (1985) Effects of chlorinated paraffins on liver weight,
    cytochrome P-450 concentration and microsomal enzyme activities in
    chick embryos. Arch Toxicol, 57: 69-71.

    BUA (German Chemical Society Advisory Committee on Existing Chemicals
    of Environmental Relevance) (1992) [Chlorinated paraffins.] Weinheim,
    VCH Verlagsgesellschaft, 227 pp (BUA Report 93) (in German).

    Bucher JR, Alison RH, Montgomery CA, Huff J, Haseman JK, Farnell
    D, Thompson R, & Prejean JD (1987) Comparative toxicity and
    carcinogenicity of two chlorinated paraffins in F344/N rats and
    B6C3F1 mice. Fundam Appl Toxicol, 9: 454-468.

    Camford Information Services (1991) CPI product profiles: chlorinated
    paraffins. Don Mills, Ontario, Camford Information Services, 3 pp.

    Campbell I & McConnell G (1980) Chlorinated paraffins and the
    environment. 1. Environmental occurrence. Environ Sci Technol,
    14: 1209-1214.

    Conz A & Fumero S (1988a) Study of the capacity of Solvocaffaro C1642
    to induce gene mutations in strains of  Salmonella typhimurium.
    Turin, Istituto di Recerche Biomediche "Antoine Marxer", 37 pp (RBM
    Exp. No. 880367).

    Conz A & Fumero S (1988b) Micronucleus induction in bone marrow cells
    of mice treated by oral route with the test article Solvocaffaro
    C1642. Turin, Istituto di Recerche Biomediche "Antoine Marxer", 20 pp
    (RBM Exp. No. 880368).

    Cooke M & Roberts DJ (1980) Carbon skeleton capillary gas
    chromatography. J Chromatogr, 193: 437-443.

    Darnerud PO (1984) Chlorinated paraffins: Effect of some microsomal
    enzyme inducers and inhibitors of the degradation of 1-14C-chloro-
    dodecanes to 14CO2 in mice. Acta Pharmacol Toxicol,
    55: 110-115.

    Darnerud PO & Brandt I (1982) Studies on the distribution and
    metabolism of a 14C-labelled chlorinated alkane in mice. Environ
    Pollut, A27: 45-56.

    Darnerud PO & Lundkvist U (1987) Studies on implantation and embryonic
    development in mice given a highly chlorinated hexadecane. Pharmacol
    Toxicol, 60: 239-240.

    Darnerud PO, Biessmann A, & Brandt I (1982) Metabolic fate of
    chlorinated paraffins: degree of chlorination of [1-14C]-chloro-
    dodecanes in relation to degradation and excretion in mice. Arch
    Toxicol, 50: 217-226.

    Darnerud PO, Bengtsson BE, Bergman A, & Brandt I (1983) Chlorinated
    paraffins: disposition of a polychloro-[1-14C]-hexadecane in carp
     (Cyprinus carpio) and bleak  (Alburnus alburnus). Toxicol Lett,
    19: 345-351.

    Darnerud PO, Bergman Å, Lund BO, & Brandt I (1989) Selective
    accumulation of chlorinated paraffins (C12 and C16) in the olfactory
    organ of rainbow trout. Chemosphere, 18: 1821-1827.

    EG & G Bionomics (1983) The acute and chronic toxicity of a chlorinated
    paraffin (58% chlorination of short chain length  n-paraffins) to
    midges  (Chironomus tentans). Wareham, Massachusetts, EG & G Bionomics,
    39 pp (Report No. BW 83-6-1426).

    Elcombe CR, Watson SC, Wyatt I, & Foster JR (1994) Chlorinated
    paraffins (CP): Mechanisms of carcinogenesis. Toxicologist, 14: 276.

    Elcombe CR, Bars RG, Watson SC, & Foster JR (in press) Hepatic effects
    of chlorinated paraffins in mice, rats and guinea pigs: Species
    differences and implications for hepatocarcinogenicity. Xenobiotica.

    Elliott BM (1989a) Meflex DC029 (fully formulated) - Ames test.
    Macclesfield, Cheshire, Imperial Chemical Industries Ltd, 1 p (Report
    No. CTL/L/2668).

    Elliott BM (1989b) Meflex DC029 (fully formulated) - Mouse
    micronucleus test. Macclesfield, Cheshire, Imperial Chemical
    Industries Ltd, 1 p (Report No. CTL/L/2693).

    English JSC, Foulds I, White IR, & Rycroft JG (1986) Allergic contact
    sensitization to the glycidyl ester of hexahydrophthalic acid in a
    cutting oil. Contact Dermatitis, 15: 66-69.

    Environment Agency, Japan (1981) Environmental monitoring of chemicals:
    Annual report. Tokyo, Environment Agency, p 23.

    Environment Agency, Japan (1983) Environmental monitoring of chemicals:
    Annual report. Tokyo, Environment Agency, p 75.

    Eriksson P & Darnerud PO (1985) Distribution and retention of some
    chlorinated hydrocarbons and a phthalate in the mouse brain during the
    pre-weaning period. Toxicology, 37: 189-203.

    Eriksson P & Kihlström J (1985) Disturbance of motor performance and
    thermoregulation in mice given two commercial chlorinated paraffins.
    Bull Environ Contam Toxicol, 34: 205-209.

    Eriksson P & Nordberg A (1986) The effects of DDT, DDOH-palmitic
    acid, and a chlorinated paraffin on muscarinic receptors and the
    sodium-dependent choline uptake in the central nervous system of
    immature mice. Toxicol Appl Pharmacol, 85: 121-127.

    Frank U & Steinhäuser KG (in press) [Ecotoxicity of poorly soluble
    substances tested by  Daphnia toxicity of chlorinated paraffins.] Vom
    Wasser, 83 (in German).

    Friedman D & Lombardo P (1975) Photochemical technique for the
    elimination of chlorinated aromatic interferences in the gas-liquid
    chromatographic analysis for chlorinated paraffins. J Assoc Off Anal
    Chem, 58: 703-706.

    Gjos N & Gustavsen K (1982) Determination of chlorinated paraffins by
    negative ion chemical ionization mass spectrometry. Anal Chem,
    54: 1316-1318.

    Hansen J, Schneider T, Olsen JH, & Laursen B (1992) Availability of
    data on humans potentially exposed to suspected carcinogens in the
    Danish working environment. Pharmacol Toxicol, 72(Suppl 1): S77-S85.

    Hardie DWF (1964) Chlorocarbons and chlorohydrocarbons: Chlorinated
    paraffins. In: Kirk-Othmer encyclopedia of chemical technology. New
    York, John Wiley and Sons, vol 5, pp 231-240.

    Haux C, Larsson Å, Lidman U, Förlin L, Hansson T, & Johansson-Sjöbeck
    M-L (1982) Sublethal physiological effects of chlorinated paraffins on
    the flounder,  Platichtys flesus L. Ecotoxicol Environ Saf, 6: 49-59.

    Hill RW & Maddock BG (1983) Effect of a chlorinated paraffin (58%
    chlorination of short chain length  n-paraffins) on embryos and
    larvae of the sheepshead minnow  (Cyprinodon variegatus)-(study one).
    Brixham, Imperial Chemical Industries Ltd, Brixham Laboratory, 57 pp
    (Report No. BL/B/2326).

    Hoechst (1983a) [Chloroparaffin 70 liquid NV - Acute dermal
    irritation/corrosion in rabbits.] Frankfurt/Main, Hoechst AG, 11 pp
    (Report No. 83.0444) (in German).

    Hoechst (1983b) [Hordalub 80 + TNPP - Magnusson and Kligman's test for
    sensitising properties on Pirbright-White Guinea Pigs.] Frankfurt/Main,
    Hoechst AG, 17 pp (Report No. 83.0573) (in German).

    Hoechst (1984) [Hordalub 80 HT - Magnusson and Kligman's test for
    sensitising properties on Pirbright-White Guinea Pigs.] Frankfurt/Main,
    Hoechst AG, 18 pp (Report No. 84.0458) (in German).

    Hoechst (1986a) Hordalub 80 - Study of the mutagenic potential in
    strains of  Salmonella typhimurium (Ames Test) and  Escherichia coli.
    Frankfurt/Main, Hoechst AG, 28 pp (Report No. 86.1078).

    Hoechst (1986b) [Acute dermal irritation/corrosion in rabbits.]
    Frankfurt/Main, Hoechst AG, 12 pp (Report No. 86.1105) (in German).

    Hoechst (1987) Chloroparaffin 56 liquid - Detection of gene mutations
    in somatic cells in culture. HGPRT-test with V79 cells. Frankfurt/Main,
    Hoechst AG, 23 pp (Report No. 87.1719).

    Hoechst (1988) Chloroparaffin 56 liquid (unstabilized) - Study of the
    mutagenic potential in strains of  Salmonella typhimurium (Ames Test)
    and  Escherichia coli. Frankfurt/Main, Hoechst AG, 30 pp (Report No.
    88.0099).

    Hoechst (1989) Chlorowax 500C micronucleus test in male and female
    NMRI mice after oral administration. Frankfurt/Main, Hoechst AG, 24 pp
    (Report No. 89.0253).

    Hollies JI, Pinnington DF, Handley AJ, Baldwin MK, & Bennett D (1979)
    The determination of chlorinated long-chain paraffins in water,
    sediment and biological samples. Anal Chim Acta, 111: 201-213.

    Houghton KL (1993) Chlorinated paraffins. In: In: Kirk-Othmer
    encyclopedia of chemical technology. New York, John Wiley and Sons,
    vol 6, pp 78-87.

    Howard PH, Santodonato J, & Saxena J (1975) Investigations of selected
    potential environmental contaminants: chlorinated paraffins. Syracuse,
    New York, Syracuse University Research Corporation, 107 pp (Report No.
    68-01-3101).

    HSE (1992) Chlorinated paraffins. London, Health and Safety Executive,
    44 pp (Unpublished document).

    IARC (1990) Chlorinated paraffins. In: Some flame retardants and
    textile chemicals, and exposures in the textile manufacturing
    industry. Lyon, International Agency for Research on Cancer, pp 55-72
    (IARC Monographs on the Evaluation of Carcinogenic Risks to Humans,
    Volume 48).

    ICI (1965) Toxicological report: chlorinated hydrocarbons with added
    stabilizers: "Cereclor" P70 and 70L. Macclesfield, Cheshire, Imperial
    Chemical Industries Ltd, 15 pp (Report No. CTL/TR/464).

    ICI (1966) Toxicological report: 40% chlorinate of C10-13 normal
    paraffin. Macclesfield, Cheshire, Imperial Chemical Industries Ltd,
    4 pp (Report No. CTL/TR/524).

    ICI (1967) Toxicological report: "Cereclor" 50LV (MD.115) - 50%
    chlorinate of C10-13 normal paraffin. Macclesfield, Cheshire, Imperial
    Chemical Industries Ltd, 4 pp (Report No. CTL/TR/618).

    ICI (1968) Toxicological report: fire-resistant hydraulic fluid
    10B/1067. Macclesfield, Cheshire, Imperial Chemical Industries Ltd,
    7 pp (Report No. CTL/TR/635).

    ICI (1969) Toxicological report: skin irritancy and oral toxicity of
    chlorinated paraffins. Macclesfield, Cheshire, Imperial Chemical
    Industries Ltd, 11 pp (Report No. CTL/TR/691).

    ICI (1971) Toxicological report: fire-resistant hydraulic fluid
    45D-3271. Macclesfield, Cheshire, Imperial Chemical Industries Ltd,
    8 pp (Report No. CTL/T/831).

    ICI (1973) "Cereclor" 63L: local irritancy and acute oral toxicity.
    Macclesfield, Cheshire, Imperial Chemical Industries Ltd, 7 pp (Report
    No. CTL/T/938).

    ICI (1974a) "Cereclors" and "Hordolub": local irritancy and acute
    toxicity. Macclesfield, Cheshire, Imperial Chemical Industries Ltd,
    32 pp (Report No. CTL/T/962).

    ICI (1974b) "Cereclor" 50 HS: summary of local irritancy, skin
    sensitization and acute toxicity. Macclesfield, Cheshire, Imperial
    Chemical Industries Ltd, 3 pp (Report No. CTL/Z/0548).

    ICI (1975a) "Cereclor" 60 HS: primary skin irritation in rabbits.
    Macclesfield, Cheshire, Imperial Chemical Industries Ltd, 3 pp (Report
    No. CTL/Z/0813).

    ICI (1975b) "Cereclor" 50 HS: primary skin irritation in rabbits.
    Macclesfield, Cheshire, Imperial Chemical Industries Ltd, 3 pp (Report
    No. CTL/Z/0812).

    ICI (1980) Cloparin 1049 and "Meflex" DC029: a comparison of skin
    irritation potential. Macclesfield, Cheshire, Imperial Chemical
    Industries Ltd, 11 pp (Report No. CTL/T/1431).

    ICI (1982a) Cell transformation test for potential carcinogenicity of
    chlorinated paraffin (58% chlorination of short chain length
     n-paraffins). Macclesfield, Cheshire, Imperial Chemical Industries
    Ltd.

    ICI (1982b) Cell transformation test for potential carcinogenicity
    of chlorinated paraffin (70% chlorination of short chain length
     n-paraffins). Macclesfield, Cheshire, Imperial Chemical Industries
    Ltd.

    ICI (1982c) Cloparin 59: skin irritation study. Macclesfield,
    Cheshire, Imperial Chemical Industries Ltd, 14 pp (Report No.
    CTL/T/1737).

    Inveresk (1975) Patch testing of textile lubricants. Musselburgh,
    Inveresk Research International, 14 pp (Report No. 318).

    IRDC (1981a) 14-Day oral toxicity study in rats. Chlorinated paraffin:
    58% chlorination of short chain length  n-paraffins. Mattawan,
    Michigan, International Research and Development Corporation, 110 pp
    (Report No. 438-006).

    IRDC (1981b) 14-Day oral toxicity study in rats. Chlorinated paraffin:
    52% chlorination of long chain length  n-paraffins. Mattawan,
    Michigan, International Research and Development Corporation, 104 pp
    (Report No. 438-005).

    IRDC (1982a) Teratology study in rats. Chlorinated paraffin: 58%
    chlorination of short chain length  n-paraffins. Mattawan, Michigan,
    International Research and Development Corporation, 100 pp (Report
    No. 438-016).

    IRDC (1982b) 14-Day oral toxicity study in rats. Chlorinated paraffin:
    70% chlorination of long chain length  n-paraffins. Mattawan,
    Michigan, International Research and Development Corporation, 103 pp
    (Report No. 438/004).

    IRDC (1982c) 14-Day oral (gavage) toxicity study in rats. Chlorinated
    paraffin: 43% chlorination of long chain length  n-paraffins.
    Mattawan, Michigan, International Research and Development Corporation,
    110 pp (Report No. 438/005).

    IRDC (1982d) Teratology study in rabbits. Chlorinated paraffin: 58%
    chlorination of short chain length  n-paraffins. Mattawan, Michigan,
    International Research and Development Corporation, 95 pp (Report
    438-031).

    IRDC (1982e) Teratology study in rabbits. Chlorinated paraffin: 43%
    chlorination of long chain length  n-paraffins. Mattawan, Michigan,
    International Research and Development Corporation, 102 pp (Report
    438-030).

    IRDC (1983a) Dominant lethal study in rats. Chlorinated paraffin: 58%
    chlorination of short chain  n-paraffins. Mattawan, Michigan,
    International Research and Development Corporation, 54 pp (Report
    No. 438-011).

    IRDC (1983b) Teratology study in rabbits. Chlorinated paraffin: 70%
    chlorination of long chain length  n-paraffins. Mattawan, Michigan,
    International Research and Development Corporation, 245 pp (Report
    No. 438-045).

    IRDC (1983c) 14-Day dietary range-finding study in rats. Chlorinated
    paraffin: 58% chlorination of short chain length  n-paraffins.
    Mattawan, Michigan, International Research and Development Corporation,
    136 pp (Report No. 438-002).

    IRDC (1983d) Teratology study in rats. Chlorinated paraffin: 43%
    chlorination of long chain length  n-paraffins. Mattawan, Michigan,
    International Research and Development Corporation, 197 pp (Report
    No. 438-015).

    IRDC (1983e)  In vivo cytogenetic evaluation by analysis of rat bone
    marrow cells. Chlorinated paraffin: 70% chlorination of long chain
    length paraffins. Mattawan, Michigan, International Research and
    Development Corporation, 70 pp (Report No. 438-016).

    IRDC (1983f) Teratology study in rabbits. Chlorinated paraffin: 52%
    chlorination of intermediate chain length  n-paraffins. Mattawan,
    Michigan, International Research and Development Corporation, 195 pp
    (Report No. 438-032).

    IRDC (1983g)  In vivo cytogenetic evaluation by analysis of rat bone
    marrow cells. Chlorinated paraffin: 52% chlorination of intermediate
    chain length  n-paraffins. Mattawan, Michigan, International Research
    and Development Corporation, 62 pp (Report No. 438-014).

    IRDC (1983h)  In vivo cytogenetic evaluation by analysis of rat bone
    marrow cells. Chlorinated paraffins: 58% chlorination of short chain
    length  n-paraffins. Mattawan, Michigan, International Research and
    Development Corporation, 58 pp (Report No. 438-013).

    IRDC (1983i)  In vivo cytogenetic evaluation by analysis of rat bone
    marrow cells. Chlorinated paraffin: 43% chlorination of long chain
    length  n-paraffins. Mattawan, Michigan, International Research and
    Development Corporation, 56 pp (Report No. 438-012).

    IRDC (1984a) 13-week oral (gavage) toxicity study in rats with
    combined excretion, tissue level and elimination studies: determination
    of excretion, tissue level and elimination after single oral (gavage)
    administration to rats. Chlorinated paraffin: 58% chlorination of short
    chain length  n-paraffins; 14C labeled CP. Mattawan, Michigan,
    International Research and Development Corporation, 350 pp (Report
    No. 438-029/022).

    IRDC (1984b) 13-week oral (dietary) toxicity study in rats with
    combined excretion, tissue level and elimination studies: determination
    of excretion, tissue level and elimination after single oral (gavage)
    administration to rats. Chlorinated paraffin: 52% chlorination of
    intermediate chain length  n-paraffins, 14C labeled CP. Mattawan,
    Michigan, International Research and Development Corporation, 328 pp
    (Report No. 438-023/026).

    IRDC (1984c) 13-week oral (dietary) toxicity study in rats with
    combined excretion, tissue level and elimination study: determination
    of excretion, tissue level and elimination after single oral (gavage)
    administration to rats. Chlorinated paraffin: 58% chlorination of
    short chain length  n-paraffins; 14C labeled CP. Mattawan, Michigan,
    International Research and Development Corporation, 435 pp (Report
    No. 438-035/022).

    IRDC (1984d) Teratology study in rats. Chlorinated paraffin: 52%
    chlorination of intermediate chain length  n-paraffins. Mattawan,
    Michigan, International Research and Development Corporation, 105 pp
    (Report No. 438-017).

    IRDC (1984e) Teratology study in rats. Chlorinated paraffin: 70%
    chlorination of long chain length  n-paraffins. Mattawan, Michigan,
    International Research and Development Corporation, 99 pp (Report
    No. 438/045).

    IRDC (1984f) 13-week oral (gavage) toxicity study in rats with
    combined excretion, tissue level and elimination study: determination
    of excretion, tissue level and elimination after single oral (gavage)
    administration to rats. Chlorinated paraffin: 43% chlorination of long
    chain length  n-paraffins; 14C labeled CP. Mattawan, Michigan,
    International Research and Development Corporation, 275 pp (Report
    No. 438-028/021).

    IRDC (1984g) 13-week dietary toxicity study in rats with combined
    excretion, tissue level and elimination studies/determination of
    excretion, tissue level and elimination after single oral (gavage)
    administration to rats. Chlorinated paraffin: 70% chlorination of long
    chain length  n-paraffins; 14C labeled CP. Mattawan, Michigan,
    International Research and Development Corporation, 316 pp (Report
    No. 438-027/024).

    IRDC (1985) Reproduction range-finding study in rats. Chlorinated
    paraffin: 52% chlorination of intermediate chain length  n-paraffins.
    Mattawan, Michigan, International Research and Development Corporation,
    179 pp (Report No. 438-049).

    Jansson B, Andersson R, Asplund L, Bergman Å, Litze'n K, Nylund K,
    Reuthergårdh L, Sellström U, Uvemo U-B, Wahlberg C, & Wideqvist U
    (1991) Multiresidue method for the gas-chromatographic analysis of
    some polychlorinated and polybrominated pollutants in biological
    samples. Fresenius J Anal Chem, 340: 439-445.

    Jansson B, Andersson R, Asplund L, Litze'n K, Nylund K, Sellström U,
    Uvemo U-B, Wahlberg C, Wideqvist U, Odsjö T, & Olsson M (1993)
    Chlorinated and brominated persistent organic compounds in biological
    samples from the environment. Environ Toxicol Chem, 12: 1163-1174.

    KEMI (1991) Chlorinated paraffins. In: Freij L ed. Risk reduction of
    chemicals: A Government Commission Report. Solna, The Swedish National
    Chemicals Inspectorate, pp 167-187 (KEMI Report 1/91).

    Kraemer W & Ballschmiter K (1987) Detection of a new class of
    organochlorine compounds in the marine environment: the chlorinated
    paraffins. Fresenius Z Anal Chem, 327: 47-48.

    Lindén E, Bengtsson BE, Svanberg O, & Sundström G (1979) The acute
    toxicity of 78 chemicals and pesticide formulations against two
    brackish water organisms, the bleak  (Alburnus alburnus) and the
    harpacticoid  Nitocra spinipes. Chemosphere, 8: 843-851.

    Lombardo P, Dennison JL, & Johnson WW (1975) Bioaccumulation of
    chlorinated paraffin residues in fish fed Chlorowax 500C. J Assoc Off
    Anal Chem, 58: 707-710.

    Lundberg P (1980) Effects of some flame retardants on the liver
    microsomal enzyme systems. In: Cohn MJ ed. Microsomes, drug
    oxidations, and chemical carcinogenesis, 1979. New York, Academic
    Press, pp 853-856.

    Lunde G & Steinnes E (1975) Presence of lipid-soluble chlorinated
    hydrocarbons in marine oils. Environ Sci Technol, 9: 155-157.

    Madeley J & Birtley R (1980) Chlorinated paraffins and the
    environment. 2. Aquatic and avian toxicology. Environ Sci Technol,
    14: 1215-1221.

    Madeley JR & Gillings E (1983) Determination of the solubility of four
    chlorinated paraffins in water. Brixham, Imperial Chemical Industries
    Ltd, Brixham Laboratory, 23 pp (Report No. BL/B/2301).

    Madeley JR & Maddock BG (1983a) Effects of a chlorinated paraffin on
    the growth of rainbow trout. Chlorinated paraffin: 58% chlorination of
    short chain length paraffins. Brixham, Imperial Chemical Industries
    Ltd, Brixham Laboratory, 67 pp (Report No. BL/B/2309).

    Madeley JR & Maddock BG (1983b) The bioconcentration of a chlorinated
    paraffin in the tissues and organs of rainbow trout  (Salmo gairdneri).
    Brixham, Imperial Chemical Industries Ltd, Brixham Laboratory, 39 pp
    (Report No. BL/B/2310).

    Madeley JR & Maddock BG (1983c) Toxicity of a chlorinated paraffin to
    rainbow trout over 60 days. Chlorinated paraffin: 52% chlorination of
    intermediate chain length  n-paraffins. Brixham, Imperial Chemical
    Industries Ltd, Brixham Laboratory, 69 pp (Report No. BL/B/2202).

    Madeley JR & Maddock BG (1983d) Toxicity of a chlorinated paraffin to
    rainbow trout over 60 days. Chlorinated paraffin: 43% chlorination of
    long chain length  n-paraffins. Brixham, Imperial Chemical Industries
    Ltd, Brixham Laboratory, 71 pp (Report No. BL/B/2201).

    Madeley JR & Thompson RS (1983a) Toxicity of chlorinated paraffins to
    mussels  (Mytilus edulis) over 60 days. Chlorinated paraffin: 58%
    chlorination of short chain length  n-paraffins. Brixham, Imperial
    Chemical Industries Ltd, Brixham Laboratory, 71 pp (Report No.
    BL/B/2291).

    Madeley JR & Thompson RS (1983b) Toxicity of chlorinated paraffins to
    mussels  (Mytilus edulis) over 60 days. Chlorinated paraffin: 52%
    chlorination of intermediate chain length  n-paraffins. Brixham,
    Imperial Chemical Industries Ltd, Brixham Laboratory, 53 pp (Report
    No. BL/B/2289).

    Madeley JR & Thompson RS (1983c) Toxicity of chlorinated paraffins to
    mussels  (Mytilus edulis) over 60 days. Chlorinated paraffin: 43%
    chlorination of long chain length  n-paraffins. Brixham, Imperial
    Chemical Industries Ltd, Brixham Laboratory, 59 pp (Report No.
    BL/B/2288).

    Madeley JR & Thompson RS (1983d) Toxicity of chlorinated paraffins to
    mussels  (Mytilus edulis) over 60 days. Chlorinated paraffin: 70%
    chlorination of long chain length  n-paraffins. Brixham, Imperial
    Chemical Industries Ltd, Brixham Laboratory, 64 pp (Report No.
    BL/B/2290).

    Madeley JR, Thompson RS, & Brown D (1983a) The bioconcentration of a
    chlorinated paraffin by common mussel  (Mytilus edulis). Chlorinated
    paraffin: 58% chlorination of short chain length  n-paraffins.
    Brixham, Imperial Chemical Industries Ltd, Brixham Laboratory, 76 pp
    (Report BL/B/2351).

    Madeley JR, Windeatt AJ, & Street JR (1983b) Assessment of the
    toxicity of a chlorinated paraffin to the anaerobic sludge digestion
    product. Chlorinated paraffin: 58% chlorination of short chain length
     n-paraffins. Brixham, Imperial Chemical Industries Ltd, Brixham
    Laboratory, 25 pp (Report No. BL/B/2253).

    Mather JI, Street JR, & Madeley JR (1983) Assessment of the inherent
    biodegradability of a chlorinated paraffin, under aerobic conditions,
    by a method developed from OECD Test Guideline 302B. Chlorinated
    paraffin: 58% chlorination of short chain length  n-paraffins.
    Brixham, Imperial Chemical Industries Ltd, Brixham Laboratory, 56 pp
    (Report No. BL/B/2298).

    Meijer J & DePierre JW (1987) Hepatic levels of cytosolic, microsomal
    and "mitochondrial" epoxide hydrolases and other drug-metabolizing
    enzymes after treatment of mice with various xenobiotics and endogenous
    compounds. Chem-Biol Interact, 62: 249-269.

    Meijer J, Rundgren M, Åström A, DePierre JW, Sundvall A, & Rannug U
    (1981) Effects of chlorinated paraffins on some drug-metabolizing
    enzymes in rat liver and in the Ames test. Adv Exp Med Biol,
    A136: 821-828.

    Menter P, Harrison W, & Woodin WG (1975) Patch testing of coolant
    fractions. J Occup Med, 17(9): 565-568.

    Muller W (1989) Chlorowax 500C - Micronucleus test in male and female
    NMRI mice after oral administration. Frankfurt/Main, Hoechst AG,
    Pharma Research Toxicology and Pathology, 24 pp (Report No. 89.0253).

    Murray T, Frankenberry M, Steele DH, & Heath RG (1988) Chlorinated
    paraffins: A report on the findings from two field studies, Sugar
    Creek, Ohio, Tinkers Creek, Ohio. Volume 1: Technical report.
    Washington, DC, US Environmental Protection Agency, 150 pp (EPA-560/
    5-87/012).

    Myhr B, McGregor D, Bowers L, Riach C, Brown AG, Edwards I, McBride D,
    Martin R, & Caspary WJ (1990) L5178Y mouse lymphoma cell mutation
    assay results with 41 compounds. Environ Mol Mutagen, 16(Suppl 18):
    138-167.

    NIOSH (1990) National occupational exposure survey (1980-1983).
    Cincinnati, Ohio, National Institute for Occupational Safety and
    Health.

    Nilsen O & Toftgård R (1981) Effect of polychlorinated terphenyls and
    paraffins on rat liver microsomal cytochrome P-450 and  in vitro
    metabolic activities. Arch Toxicol, 47: 1-11.

    Nilsen O, Toftgård R, & Glaumann H (1980) Changes in rat liver
    morphology and metabolic activities after exposure to chlorinated
    paraffins. Dev Toxicol Environ Sci, 8: 525-528.

    Nilsen OG, Toftgård R, & Glaumann H (1981) Effects of chlorinated
    paraffins on rat liver microsomal activities and morphology.
    Importance of the length and the degree of chlorination of the carbon
    chain. Arch Toxicol, 49: 1-13.

    NTP (1986a) Toxicology and carcinogenesis studies of chlorinated
    paraffins (C12, 60% chlorine) (CAS No. 63449-39-8) in F344/N rats and
    B6C3F1 mice (gavage studies). Research Triangle Park, North Carolina,
    US Department of Health and Human Services, National Toxicology
    Program, 67 pp (Technical Report Series No. 308).

    NTP (1986b) Toxicology and carcinogenesis studies of chlorinated
    paraffins (C23, 43% chlorine) (CAS No. 63449-39-8) in F344/N rats and
    B6C3F1 mice (gavage studies). Research Triangle Park, North Carolina,
    US Department of Health and Human Services, National Toxicology
    Program, 66 pp (Technical Report Series No. 305).

    Omori T, Kimura T, & Kodama T (1987) Bacterial cometabolic degradation
    of chlorinated paraffins. Appl Microbiol Biotechnol, 25: 553-557.

    Poon R, LeCavalier P, Chan P, Viau C, Håkansson H, Chu I, & Valli VE
    (in press) Subchronic toxicity of a medium-chain chlorinated paraffin
    in the rat. J Appl Toxicol.

    Renberg L, Sundström G, & Sundh-Nygård K (1980) Partition coefficients
    of organic chemicals derived from reversed-phase thin-layer
    chromatography. Evaluation of methods and application on phosphate
    esters, polychlorinated paraffins and some PCB-substitutes.
    Chemosphere, 9: 683-691.

    Renberg L, Tarkpea M, & Sundström G (1986) The use of the bivalve
     Mytilus edulis as a test organism for bioconcentration studies. II.
    The bioconcentration of two 14C-labeled chlorinated paraffins.
    Ecotoxicol Environ Saf, 11: 361-372.

    Richold M, Allen JA, Williams A, & Ransome SJ (1982a) Cell
    transformation test for potential carcinogenicity of chlorinated
    paraffin (58% chlorination of short chain length  n-paraffins).
    Huntingdon, Huntingdon Research Centre, 40 pp (Report No. ICI
    399C/81468).

    Richold M, Allen JA, Williams A, & Ransome SJ (1982b) Cell
    transformation test for potential carcinogenicity of chlorinated
    paraffin (70% chlorination of long chain length  n-paraffins).
    Huntingdon, Huntingdon Research Centre, 30 pp (Report No. ICI
    399A/415/82313).

    Roberts DJ, Cooke M, & Nickless G (1981) Determination of poly-
    chlorinated alkanes via carbon skeleton capillary gas chromatography.
    J Chromatogr, 213: 73-81.

    Schenker BA (1979) Chlorinated paraffins. In: Mark HF, Othmer DF,
    Overberger CG, Seaborg GT, & Grayson M ed. Kirk-Othmer encyclopedia of
    chemical technology. New York, John Wiley and Sons, vol 5, pp 786-791.

    Schmid PP & Müller MD (1985) Trace level detection of chlorinated
    paraffins in biological and environmental samples, using gas
    chromatography/mass spectrometry with negative-ion chemical ionization.
    J Assoc Off Anal Chem, 68: 427-430.

    Scott RC (1989)  In vitro absorption of some chlorinated paraffins
    through human skin. Arch Toxicol, 63: 425-426.

    Serrone DM, Birtley RDN, Weigand W, & Millischer R (1987) Toxicology
    of chlorinated paraffins. Food Chem Toxicol, 25: 553-562.

    Shults SK, Serrone DM, Killeen JC, & Ignatoski JA (1984) A one-
    generation reproduction study in mallard ducks with chlorinated
    paraffins. Painesville, Ohio, SDS Biotech Corporation, 273 pp (Report
    No. 558-1IT-83-0032-003).

    Sistovaris N & Donges V (1987) Gas chromatographic determination of
    total polychlorinated aromates and chloro-paraffins following
    catalytic reduction in the injection port. Fresenius Z Anal Chem,
    326: 751-753.

    Slooff W, Bont PFH, Janus JA, & Annema JA (1992) Exploratory report on
    chlorinated paraffins. Bilthoven, The Netherlands, National Institute
    of Public Health and Environmental Protection, 47 pp (Report No.
    710401016).

    Steele DH, Sack TM, Moody LA, Murray TM, Glatz JA, & Breen JJ (1988) A
    negative chemical ionization GC/MS method for the determination of
    chlorinated paraffins in environmental samples. Presented at the 36th
    ASMS Conference on Mass Spectrometry and Allied Topics, San Francisco,
    5-10 June 1988. New York, American Society for Mass Spectrometry,
    2 pp.

    Strack H (1986) Chlorinated paraffins. In: Ullmann's encyclopedia of
    industrial chemistry. Weinheim, VCH Verlagsgesellschaft, vol A6,
    pp 323-330.

    Street JR & Madeley JR (1983a) Summary of experiments conducted in an
    attempt to determine the biodegradability of a chlorinated paraffin
    under anaerobic conditions by EPA test guide line CG2050. Brixham,
    Imperial Chemical Industries Ltd, Brixham Laboratory, 23 pp (Report
    BL/B/2363).

    Street JR & Madeley JR (1983b) Assessment of the fate of a chlorinated
    paraffin during aerobic sewage treatment by a modification of OECD
    test guideline 303A. Brixham, Imperial Chemical Industries Ltd,
    Brixham Laboratory, 70 pp (Report No. BL/B/2308).

    Swedish Environment Protection Agency (1994) Chlorinated paraffins in
    metal working. Solna, Swedish Environment Protection Agency, 10 pp
    (SEPA Report No. 4372).

    Tarkpea M, Lindén E, Bengtsson BE, Larsson Å, & Svanberg O (1981)
    [Products control studies at the Brackish Water Toxicology Laboratory,
    1979-80.] Nyköping, Swedish Environmental Protection Agency, 22 pp
    (NBL Report 1981-03-23) (in Swedish).

    Thompson RS & Madeley JR (1983a) The acute and chronic toxicity of a
    chlorinated paraffin (58% chlorination of short chain length
     n-paraffins) to the mysid shrimp  Mysidopsis bahia. Brixham, Imperial
    Chemical Industries Ltd, Brixham Laboratory, 55 pp (Report No.
    BL/B/2373).

    Thompson RS & Madeley JR (1983b) Toxicity of a chlorinated paraffin
    (58% chlorination of short chain length  n-paraffins) to the marine
    alga  Skeletonema costatum. Brixham, Imperial Chemical Industries
    Ltd, Brixham Laboratory, 57 pp (Report No. BL/B/2325).

    Thompson RS & Madeley JR (1983c) The acute and chronic toxicity of a
    chlorinated paraffin (58% chlorination of short chain length
     n-paraffins) to  Daphnia magna. Brixham, Imperial Chemical Industries
    Ltd, Brixham Laboratory, 70 pp (Report No. BL/B/2358).

    Thompson RS & Madeley JR (1983d) Toxicity of a chlorinated paraffin
    (58% chlorination of short chain length  n-paraffins) to the green
    alga  Selenastrum capricornutum. Brixham, Imperial Chemical Industries
    Ltd, Brixham Laboratory, 59 pp (Report No. BL/B/2325).

    Thompson RS & Shillabeer N (1983) Effect of a chlorinated paraffin
    (58% chlorination of short chain length  n-paraffins) on the growth
    of mussels  (Mytilus edulis). Brixham, Imperial Chemical Industries
    Ltd, Brixham Laboratory, 54 pp (Report No. BL/B/2331).

    US EPA (1993) RM2 exit briefing on chlorinated paraffins and olefins.
    Washington, DC, US Environmental Protection Agency, 42 pp.

    Willis B, Diment J, Dobson S, & Crookes M (1994) Environmental hazard
    assessment: Chlorinated paraffins. Garston, Watford, Building Research
    Establishment, 47 pp (Report No. TSD/19).

    Wyatt I, Coutts CT, & Elcombe CR (1993) The effect of chlorinated
    paraffins on hepatic enzymes and thyroid hormones. Toxicology,
    77: 81-90.

    Yang JJ, Roy TA, Neil W, Kreuger AJ, & Mackerer CR (1987) Percutaneous
    and oral absorption of chlorinated paraffins in the rat. Toxicol Ind
    Health, 3: 405-412.

    Zitko V (1973) Chromatography of chlorinated paraffins on alumina and
    silica columns. J Chromatogr, 81: 152-155.

    Zitko V (1974a) Uptake of chlorinated paraffins and PCB from suspended
    solids and food by juvenile atlantic salmon. Bull Environ Contam
    Toxicol, 12: 406-412.

    Zitko V (1974b) Confirmation of chlorinated paraffins by dechlor-
    ination. J Assoc Off Anal Chem, 57: 1253-1259.

    Zitko V (1980) Chlorinated paraffins. In: Hutzinger O ed. Handbook of
    environmental chemistry. Volume 3, Part A: Anthropogenic compounds.
    Berlin, Heidelberg, New York, Springer Verlag, pp 149-156.

    Zitko V & Arsenault E (1977) Fate of high molecular weight-chlorinated
    paraffins in the aquatic environment. Adv Environ Sci Technol, 8:
    409-418.

    RESUME

    1.  Propriétés, usages et méthodes d'analyse

         Les paraffines chlorées s'obtiennent par chloration des fractions
    paraffiniques à chaîne droite.  La chaîne des paraffines du commerce
    comporte habituellement 10 à 30 atomes de carbone et leur teneur en
    chlore est généralement comprise entre 40 et 70% en poids.  Ce sont
    des huiles visqueuses et denses, incolores ou jaunâtres, à faible
    tension de vapeur; toutefois, lorsque la chaîne carbonée est
    suffisamment longue et que la teneur en chlore est élevée (70%), on a
    affaire à des solides.  Les paraffines chlorées sont pratiquement
    insolubles dans l'eau, les alcools inférieurs, le glycérol et les
    glycols, mais solubles dans les solvants chlorés, les hydrocarbures
    aromatiques, les cétones, les esters, les éthers,les huiles minérales
    et certaines huiles de coupe. Elles sont modérément solubles dans les
    hydrocarbures aliphatiques non chlorés.

         En raison du nombre de positions possibles pour les atomes de
    chlore, les paraffines chlorées sont des mélanges ex trêmement
    complexes.  Selon la longueur de la chaîne (courte C10-13,
    intermédiaire C14-17, longue C18-30) et le degré de chloration (faible
    < 50%; élevé > 50%), on peut diviser ces produits en six groupes.

         Les paraffines chlorées sont très largement utilisées dans le
    monde entier pour diverses applications: plastifiants (par ex. Pour le
    PVC), additifs pour lubrifiants de pièces métalliques travaillant à
    très haute pression, retardateurs de flammes et additifs pour
    peintures.  Les produits de qualité technique peuvent contenir
    diverses impuretés: isoparaffines, métaux, composés aromatiques et en
    principe, ils sont additionnés de stabilisants destinés à en prévenir
    la décomposition.

         En raison de la très grande complexité des mélanges, l'analyse
    des paraffines chlorées est difficile.  Lorsqu'il s'agit de travailler
    sur des prélèvements effectués dans l'environnement, il s'y ajoute
    encore les interférences dues à la présence d'autres composés. 
    L'analyse proprement dite doit donc souvent être précédée d'une
    purification poussée des échantillons et faire appel à des moyens de
    détection spécifiques.  Au début, on purifiait le mélange par
    chromatographie en couche mince et on effectuait ensuite la révélation
    sur la plaque par une méthode non spécifique.  Actuellement, on
    utilise différentes techniques de chromatographie sur colonne pour la
    purification des échantillons, mais il est difficile d'isoler les
    paraffines chlorées en raison de la grande diversité de leurs
    propriétés physiques.  Dans ces conditions, il faut utiliser des
    méthodes de détection spécifiques; à l'heure actuelle, la plus
    utilisée est la chromatographie en phase gazeuse couplée à la
    spectrométrie de masse.  L'utilisation d'ions négatifs améliore encore

    la spécificité.  Toutefois, même si ces techniques élaborées
    facilitent l'analyse des paraffines chlorées, il encore impossible de
    déterminer les concentrations avec exactitude.  Les résultats publiés
    ne sont donc que des estimations.

    2.  Sources d'exposition humaine et environnementale

         On ne connaît pas de paraffines chlorées d'origine naturelle.

         Ces produits s'obtiennent par réaction du chlore gazeux sur des
    fractions paraffiniques liquides.  Il peut être nécessaire d'utiliser
    un solvant et la lumière ultraviolette sert souvent de catalyseur. 
    Pour 1985, la production mondiale de paraffines chlorées a été estimée
    à 300 000 tonnes.

         La pollution de l'environnement par les paraffines chlorées
    provient sans doute essentiellement du fait qu'elles sont d'un usage
    très répandu. Elles peuvent être déversées dans l'environnement
    lorsque des lubrifiants pour métaux ou des polymères qui en
    contiennent viennent à être dispersés sans précautions dans la nature. 
    Il peut également y avoir pollution si des paraffines chlorées passent
    dans l'environnement par lessivage de peintures ou de revêtements
    divers.  On pense que davantage de paraffines chlorées disparaissent
    dans la nature pendant la production et le transport que lors de
    l'utilisation des produits et de leur élimination.

         En raison de leur instabilité thermique, les paraffines chlorées
    doivent en principe être décomposées par l'incinération et donc ne pas
    réapparaître dans les gaz émis par les incinérateurs.  On a cependant
    montré que lors de la pyrolyse de ces produits, des dérivés chlorés
    d'hydrocarbures aromatiques-biphényle, naphtalène ou benzène
    polychlorés - peuvent se former dans certaines conditions.

    3.  Distribution et transformation dans l'environnement

         Les paraffines chlorées sont fortement adsorbées par les
    sédiments.  Dans l'eau, elles sont probablement transportées par
    les particules sur lesquelles elles sont adsorbées; dans l'air
    l'adsorption a vraisemblablement lieu sur les particules aéroportées
    (et peut être aussi dans la phase vapeur).  On estime que dans l'air,
    la demi-vie des paraffines chlorées est de 0,85 à 7,2 jours, cette
    durée étant suffisamment longue pour qu'on ne puisse exclure un
    transport sur de longues distances.

         Les paraffines chlorées ne sont pas facilement biodégradables. 
    En fait, celles qui ont une chaîne courte et une teneur en chlore
    de moins de 50% se révèlent biodégradables en aérobiose par des
    microorganismes acclimatés, la dégradation paraissant inhibée lorsque
    la teneur en chlore dépasse 58%.  La dégradation des paraffines
    chlorées à chaîne moyenne ou longue est plus lente.

         Les paraffines chlorées s'accumulent dans les organismes
    aquatiques et les facteurs de bioconcentration publiés vont de 7 à
    7155 pour les poissons et de 223 à 138 000 pour les moules.  Les
    poissons accumulent davantage les paraffines chlorées à courte chaîne
    que les composés à chaîne moyenne ou longue.  Après administration de
    produits radiomarqués, on a retrouvé la radioactivité principalement
    dans la bile, les intestins, le foie, les graisses et les branchies. 
    La fixation de ces composés semble donc facilitée par une chaîne
    courte et une faible teneur en chlore, les composés à chaîne longue,
    quant à eux, étant éliminés le plus lentement.  La rétention dans les
    tissus à forte adiposité augmente avec la teneur en chlore.

    4.  Concentrations dans l'environnement et exposition humaine

         On ne possède guère de données sur la concentration des
    paraffines chlorées dans l'environnement.  On en a décelé la présence
    au Royaume-Uni dans des échantillons d'eau de mer à des concentrations
    inférieures à 4 µg/litre.  Dans des eaux n'appartenant pas au domaine
    marin, on a mesuré dans ce même pays des concentrations inférieures à
    6 µg/litre; en Allemagne, les teneurs relevées en 1994 se situaient
    dans les limites de 0,08 à 0,28 µg/litre.  Aux Etats-Unis, la teneur
    des eaux en paraffines chlorées est en général inférieure à
    0,03 µg/litre, mais il est arrivé qu'on ait des concentrations
    supérieures à 1,0 µg/litre dans une faible proportion des échantillons
    (1,2%). Dans les sédiments marins, on a fait état de concentrations
    allant jusqu'à 600 µg/kg de poids frais, cette teneur pouvant aller, au
    Royaume-Uni, jusqu'à 15 000 µg/kg de poids frais pour des sédiments
    non marins provenant de régions industrialisées et atteindre encore
    1000 µg/kg de poids frais dans des zones à l'écart de toute industrie. 
    Aux Etats-Unis, on a trouvé, dans les eaux d'une retenue qui
    provenaient d'une usine produisant des paraffines chlorées, des
    sédiments dont la teneur atteignait, en poids sec, 170 000 µg/kg de
    dérivés à longue chaîne, 50 000 µg/kg de dérivés à chaîne moyenne et
    40 000 µg/kg de dérivés à chaîne courte.  En Allemagne, on a trouvé en
    1994 dans des sédiments les concentrations suivantes: jusqu'à 83 µg/kg
    de dérivés en C10-13 et jusqu'à 370 µg/kg de dérivés en C14-17.  Au
    Japon, la teneur des sédiments allait jusqu'à 8 500 µg/kg.

         La présence de paraffines chlorées a été mise en évidence dans un
    certain nombre d'organismes.  En Suède, on en a découvert chez des
    mammifères terrestres à des concentrations de 32 à 88 µg/kg de tissus
    (140-4400 µg/kg de lipides).  Cependant au Royaume-Uni, on n'a pas
    trouvé de paraffines chlorées chez des moutons qui paissaient à
    distance des lieux de production.  Dans ce même pays, la concentration
    allait jusqu'à 1500 µg/kg chez des oiseaux, et, en ce qui concerne les
    poissons, les teneurs pouvaient atteindre 200 µg/kg, valeur également
    relevée en Suède.  Dans des moules récoltées aux Etats-unis et au
    Royaume-Uni, on a signalé des concentrations pouvant atteindre
    400 µg/kg.  Il est vrai qu'à  proximité de la décharge d'une usine de
    paraffines chlorées, les moules en contenaient jusqu'à 12 000 µg/kg.

    Ces produits ont également été décelés lors d'autopsies dans des
    tissus humains, notamment dans les tissus adipeux (teneur médiane
    100-190 µg/kg), les reins (teneur médiane inférieure à 90 µg/kg) ainsi
    que dans le foie (teneur médiane inférieure à 90 µg/kg).  Lors d'une
    enquête de portée limitée, on a constaté que des paraffines chlorées,
    principalement des dérivés en C10-20, étaient présentes à des teneurs
    pouvant atteindre 500 µg/kg dans environ 70% des échantillons de
    denrées alimentaires.

         Les données concernant l'exposition professionnelle aux
    paraffines chlorées sont très limitées. On a constaté l'existence
    d'une très faible exposition à des aérosols de paraffines chlorées à
    chaîne courte (0,003-1,2 mg/m3), lors de l'utilisation de ces
    produits comme lubrifiants de pièces métalliques, mais on ne sait pas
    dans  quelle proportion ils sont respirables.  A partir d'un modèle
    mathématique de l'exposition et en l'absence de toute mesure de
    protection, on estime que ces lubrifiants à très forte teneur en
    paraffines chlorées à chaîne courte doivent très largement entrer en
    contact avec la peau (5-15 mg/cm2 par jour), même si l'absorption est
    vraisemblablement faibles.  Des mesures de protection devraient
    permettre de réduire l'exposition cutanée.

    5.  Cinétique et métabolisme

         La toxicocinétique des paraffines chlorées a été étudiée sur des
    animaux de laboratoire.  En ce qui concerne l'homme, les données sont
    insuffisantes.  On n'a pas suffisamment étudié les différences d'ordre
    toxicocinétique pouvant résulter des différences de longueur de
    chaîne.  On ignore le degré d'absorption des paraffines chlorées
    après administration orale, mais il semble qu'il diminue à mesure
    qu'augmentent  la longueur de la chaîne et la teneur en chlore.  Selon
    la longueur de la chaîne, l'absorption cutanée peut également être
    plus ou moins importante, mais elle devrait rester limitée (moins de
    1% d'une dose de C18 en application topique).  On ne dispose d'aucune
    donnée sur l'absorption au niveau pulmonaire.

         Les paraffines chlorées se répartissent principalement dans le
    foie, les reins, les intestins, la moelle osseuse, les tissus adipeux
    et les ovaires.  On ne dispose pas de données suffisantes sur la
    rétention de ces dérivés dans l'organisme mais semble qu'elle est plus
    longue lorsque ces produits ont une faible teneur en chlore, du fait
    d'une redistribution plus lente.  On les retrouve, accompagnées de
    leurs métabolites, dans le système nerveux central jusqu'à 30 jours
    après l'administration.  Il est possible qu'elles traversent la
    barrière foeto-placentaire.  On ne dispose pas d'informations
    suffisantes sur les voies métaboliques des paraffines chlorées, encore
    que des études à l'aide de molécules radiomarquées aient montré que le
    produit final en est le CO2.

         Les paraffines chlorées sont excrétées par la voie rénale,
    biliaire ou pulmonaire (sous la forme de CO2).  Etant donné les
    importantes variations d'une étude à l'autre, il est difficile
    d'établir la part relative de chacune de ces voies d'excrétion. 
    L'élimination totale diminue lorsque le degré de chloration augmente
    et les composés fortement chlorés sont principalement excrétés (à plus
    de 50%) sous la forme de CO2.  Il peut également y avoir excrétion
    dans le lait.

    6.  Effets sur les mammifères de laboratoire et les systèmes d'épreuve
         in vitro

         Quelle que soit la longueur de la chaîne, les paraffines chlorées
    ont une faible toxicité aiguë par voie orale.  Après administration
    d'une dose unique de produits à chaîne courte, les effets toxiques les
    plus évidents consistaient en une perte de la coordination musculaire
    et un hérissement des poils.  En s'appuyant sur le peu de données dont
    on dispose, on peut également dire que la toxicité aiguë par la voie
    respiratoire et la voie cutanée semble faible.  Après application ou
    instillation de paraffines chlorées à chaîne courte ou moyenne, on a
    observé une légère irritation de la peau (produits à chaîne moyenne)
    et des yeux.  Selon certaines études, les produits à courte chaîne ne
    provoquent pas de sensibilisation cutanée.

         Les études toxicologiques basées sur l'administration de doses
    répétées par voie orale ont montré que que le foie, les reins et la
    thyroïde sont les principales cibles des paraffines chlorées.  Dans le
    cas des composés à chaîne courte, on a constaté une augmentation du
    poids du foie au doses les plus faibles (la dose effective la plus
    faible est de 50 à 100 mg/kg de poids corporel sur une journée et la
    dose sans effet observable est de 10 mg/kg de poids corporel par
    jour).  A doses plus élevées, on a également observé une augmentation
    de l'activité des enzymes hépatiques, une prolifération du réticulum
    endoplasmique agranulaire et des peroxysomes, un accroissement de la
    synthèse réplicative de l'ADN, ainsi qu'une hypertrophie, une
    hyperplasie et une nécrose du foie.  D'autres effets ont été notés:
    diminution du poids corporel (125 mg/kg de poids corporel par jour
    chez la souris), augmentation du poids des reins (100 mg/kg de poids
    corporel par jour chez le rat), augmentation de la synthèse
    réplicative de l'ADN dans les cellules rénales (313 mg/kg de poids
    corporel par jour), et néphrose (625 mg/kg de poids corporel par jour
    chez le rat).  Par ailleurs, on a signalé une augmentation du poids de
    la thyroïde ainsi qu'une hypertrophie et une hyperplasie de cette
    glande (plus faible dose effective: 100 mg/kg de poids corporel par
    jour chez le rat) avec également un accroissement de la synthèse
    réplicative de l'ADN dans les cellules folliculaires (plus faible dose
    effective: 313 mg/kg de poids corporel par jour).  A doses plus
    élevées (1000 mg/kg de poids corporel par jour), la fonction
    thyroïdienne est affectée, comme en témoignent les taux de thyroxine
    (libre et totale) plasmatiques et l'augmentation de la thyréostimuline
    plasmatique chez le rat.

         En ce qui concerne les composés à chaîne moyenne, les effets
    observés aux doses les plus faibles sont généralement une augmentation
    du poids du foie et des reins (dose effective la plus faible chez
    le rat: 100 mg/kg de poids corporel par jour et dose sans effet
    observable chez le même animal: 10 mg/kg de poids corporel par jour). 
    A des doses analogues (dose sans effets observables de 4 mg/kg de
    poids corporel par jour) on a noté un accroissement du cholestérol
    sérique et des effets bénins "adaptatifs" consistant en modifications
    histologiques au niveau de la thyroïde.

          Dans le cas des composés à longue chaîne, les effets observés
    aux doses les plus faibles consistaient en une hépatite granulomateuse
    multifocale et et un accroissement du poids du foie chez les femelles
    (dose effective la plus faible de 100 mg/kg de poids corporel par
    jour).

         Dans la seule étude de reproduction dont on dispose, on n'a pas
    constaté d'effets nocifs chez des rats exposés à des paraffines à
    chaîne moyenne contenant 52% de chlore.  On a toutefois constaté une
    réduction de la survie et du poids corporel chez les ratons (dose la
    plus faible à laquelle on constatait une réduction non significative
    du poids corporel: 5,7-7,2 mg/kg de poids corporel par jour; dose la
    plus faible pour laquelle on constatait une réduction de la survie:
    60-70 mg/kg de poids corporel par jour).  Dans un petit nombre
    d'études consacrées aux effets, sur le développement, des paraffines
    chlorées à chaîne courte, moyenne ou longue, les effets observés sur
    la progéniture étaient imputables uniquement aux composés à chaîne
    courte, à des doses toxiques pour les mères (2000 mg/kg de poids
    corporel par jour).  Les composés à chaîne longue ou moyenne n'ont eu
    aucun effet de ce genre, même à dose très élevée (1000 à 5000 mg/kg de
    poids corporel par jour).

         Les paraffines chlorées ne semblent pas provoquer de mutations
    chez les bactéries.  Cependant, il pourrait y avoir un faible effet
    clastogène dans des cultures de cellules mammaliennes  in vitro (mais
    pas  in vivo).  Les paraffines chlorées provoqueraient également une
    transformation cellulaire  in vitro.

         Des études de cancérogénicité à long terme ont été effectuées sur
    des rats et des souris qui ont été gavées respectivement avec un
    composé à chaîne courte (C12; 58% Cl) et un composé à chaîne longue
    (C23; 43% Cl).  Chez les souris B6C3F1 ayant reçu le composé
    à chaîne courte, on a observé un accroissement de l'incidence de
    certaines tumeurs: hépatiques parmi les mâles et les femelles,
    thyroïdiennes parmi les femelles.  Chez les rats Fischer-344 exposés
    au composé à chaîne courte, il y avait augmentation des tumeurs
    hépatiques parmi les mâles et les femelles, des tumeurs rénales
    (adénomes et adénocarcinomes) parmi les mâles, des tumeurs

    thyroïdiennes parmi les femelles et des leucémies monocytaires parmi
    les mâles.  Dans le cas du composé à longue chaîne, on constaté une
    augmentation de l'incidence des lymphomes malins chez les souris mâles
    et de celle des tumeurs surrénaliennes chez les rattes.

    7.  Effets sur l'homme

         Malgré la très large utilisation qui est faite des paraffines
    chlorées, on ne connaît aucun cas d'irritation ou de sensibilisation
    cutanée.  Cette observation est corroborée par les résultats d'un
    petit nombre d'études sur des volontaires au cours desquelles on a
    observé une irritation cutanée minime, mais pas de sensibilisation.

         On n'a pas pu obtenir de données concernant d'autres effets des
    paraffines chlorées sur l'homme.

    8.  Effets sur les autres êtres vivants au laboratoire et dans leur
        milieu naturel

    On a montré que les paraffines chlorées à courte chaîne pouvaient
    provoquer des intoxications aiguës chez les invertébrés marins et les
    invertébrés d'eau douce, la valeur de la CL50 et de la CE50 allant de
    14 à 530 µg/litre.  Dans la plupart des épreuves de toxicité aiguë
    effectuées sur des invertébrés aquatiques avec des paraffines chlorées
    à chaîne moyenne ou longue, les concentrations utilisées étaient
    supérieures à la solubilité des composés dans l'eau.  Toutefois, selon
    une étude, une paraffine chlorée à chaîne moyenne serait toxique pour
    les daphnies, avec une CE50 de 37 µg/litre.  La toxicité aiguë des
    paraffines chlorées pour les poissons est faible, qu'il s'agisse de
    composés à chaîne courte, moyenne ou longue, la valeur de la CL50
    étant largement supérieure à la solubilité dans l'eau.

         Les paraffines chlorées à chaîne courte présentent une toxicité à
    long terme pour les algues, les invertébrés aquatiques et les poissons
    à des concentrations ne dépasssant pas 19,6, 8,9 et 3,1 µg/litre,
    respectivement; la concentration sans effet observable se situe entre
    2 et 5 µg/litre pour l'espèce la plus sensible étudiée.  Des produits
    à chaîne moyenne et à chaîne longue ont eu des effets chroniques
    sur des daphnies à des concentrations respectivement égales à
    20-35 µg/litre et à < 1,2-8 µg/litre.  Il semble que la toxicité à
    long terme soit faible pour les poissons.  On ne dispose d'aucune
    donnée concernant les algues.

         D'après les données limitées dont on dispose, on pense que la
    toxicité aiguë est faible pour les oiseaux.

    9.  Evaluation des risques pour la santé humaine et des effets sur
        l'environnement

         Il est probable que la nourriture soit la principale source
    d'exposition de la population générale.  D'après les données limitées
    dont on dispose au sujet des concentrations dans les denrées
    alimentaires, les estimation les plus pessimistes concernant les
    produits laitiers et les moules donnent  respectivement des apports
    journaliers de 4 et 25 µg/kg de poids corporel.  En général, les doses
    journalières calculées de paraffines chlorées se situent en dessous
    des valeurs tolérables relatives aux effets non néoplasiques ou des
    valeurs recommandées relatives aux effets néoplasiques (composés à
    chaîne courte).

         Dans la mesure où ils respectent les règles d'hygiène personnelle
    et les consignes de sécurité, les travailleurs exposés à des
    paraffines chlorées n'encourent qu'un risque minime.

         Les données disponibles montrent que les paraffines chlorées
    s'accumulent dans les tissus biologiques et sont persistantes. 
    D'après les données relatives à la concentration des dérivés à chaîne
    courte dans l'environnement, il y a un risque pour la faune
    dulçaquicole et estuarielle dans les zones proches des points de
    décharge.  Les dérivés à chaîne longue et moyenne représentent aussi
    un danger pour les invertébrés aquatiques.

         L'enrichissement des sédiments en paraffines chlorées, de même
    que les modalités de résorption et la toxicité de ces produits pour la
    faune aquatique sont l'indication d'un risque pour les organismes qui
    peuplent la vase.

    RESUMEN

    1.  Propiedades, usos y métodos analíticos

         Las parafinas cloradas (PC) se producen por la cloración de
    fracciones de parafina de cadena recta.  Por lo general, la cadena
    carbonada de las parafinas cloradas comerciales contiene de 10 a 30
    átomos de carbono, y su contenido de cloro oscila generalmente entre
    el 40% y el 70% por peso.  Las parafinas cloradas son aceites densos
    viscosos incoloros o amarillentos con bajas presiones de vapor, a
    excepción de las de cadena carbonada larga con elevado contenido
    de cloro (70%), que son sólidas.  Las parafinas cloradas son
    prácticamente insolubles en agua, alcoholes inferiores, glicerol y
    glicoles, pero son solubles en solventes clorados, hidrocarburos
    aromáticos, cetonas, ésteres, éteres, aceites minerales y algunos
    lubricantes para cuchillas.  Son medianamente solubles en
    hidrocarburos alifáticos no clorados.

         Las parafinas cloradas están formadas por mezclas sumamente
    complejas, lo que obedece a las múltiples posiciones posibles de los
    átomos de cloro.  Los productos pueden subdividirse en seis grupos,
    atendiendo a la longitud de la cadena (corta C10-13, media C14-17 y
    larga C18-30) y al grado de cloración (bajo (< 50%) y elevado
    (> 50%).

         Las parafinas cloradas se utilizan en todo el mundo en múltiples
    aplicaciones; se emplean como plastificantes en la fabricación de
    plásticos (tales como el policloruro de vinilo), como aditivos en
    fluidos para el laboreo de metales a presiones extremas, y como
    pirorretardantes y aditivos en la producción de pinturas.  Las
    parafinas cloradas de calidad técnica pueden estar contaminadas por
    isoparafinas, compuestos aromáticos y metales; por lo general
    contienen estabilizadores, añadidos para impedir la descomposición.

         El análisis de las parafinas cloradas resulta difícil debido a la
    enorme complejidad de esas mezclas.  En las muestras tomadas del medio
    ambiente, ello se ve complicado además por la interferencia de otros
    compuestos.  En muchos casos, los análisis requieren un considerable
    grado de descontaminación de las muestras y el empleo de métodos de
    detección específicos.  En el pasado, se empleaba como método de
    descontaminación la cromatografía en capa fina y un método no
    específico de detección por argentación en las placas.  En la
    actualidad se emplean métodos de descontaminación basados en la
    cromatografía líquida en diferentes columnas, aunque resulta difícil
    aislar las parafinas cloradas debido al gran número de sus propiedades
    físicas.  Por lo tanto, se emplean métodos de detección específicos;
    en la actualidad, la técnica más corriente es la cromatografía por gas
    combinada con la espectrometría de masas.  El uso de iones negativos
    permite una detección incluso más específica.  Si bien el empleo de

    esas técnicas avanzadas ha aumentado la capacidad de análisis de
    las parafinas cloradas, continúa siendo imposible determinar
    las concentraciones exactas.  Los resultados comunicados deben
    considerarse solamente estimaciones de los valores reales.

    2.  Fuentes de exposición del ser humano y del medio ambiente

         No se tiene conocimiento de la presencia en estado natural de las
    parafinas cloradas.

         Las parafinas cloradas son producto de la reacción de fracciones
    de parafina líquida con gas cloro puro.  La reacción puede requerir el
    empleo de un solvente, empleándose frecuentemente luz ultravioleta
    como catalizador.  Se estima que en 1985 la producción mundial de
    parafinas cloradas se elevó a 300 000 toneladas.

         Los usos muy difundidos de las parafinas cloradas son
    probablemente la principal fuente de contaminación ambiental.  Las PC
    podrían escapar al medio ambiente debido a la eliminación incorrecta
    de fluidos para el laboreo de metales que contienen parafinas cloradas
    o de polímeros que contienen parafinas cloradas.  La pérdida de
    parafinas cloradas como resultado de la lixiviación de pinturas y
    revestimientos podría ser también fuente de contaminación ambiental. 
    Cabe prever que las posibles pérdidas durante la producción y el
    transporte sean inferiores a las que ocurren durante el uso y
    eliminación de los productos.

         Debido a su inestabilidad térmica, es de suponer que las
    parafinas cloradas se degradan durante la incineración; por lo tanto,
    no es de esperar que se volatilicen en los gases de escape de los
    incineradores.  Sin embargo, se ha demostrado la formación de
    compuestos aromáticos clorados como, por ejemplo, bifenilos
    policlorados, naftalenas y benzinas, por pirólisis de las parafinas
    cloradas en ciertas condiciones.

    3.  Distribución y transformación en el medio ambiente

         Las parafinas cloradas experimentan una adsorción pronunciada en
    el sedimento.  En el agua son transportadas probablemente adsorbidas
    en partículas en suspensión, y en la atmósfera están adsorbidas en
    partículas transportadas por el aire (y posiblemente en la fase de
    vapor).  Se ha estimado que la semivida de las parafinas cloradas en
    el aire oscila entre 0,85 y 7,2 días; debido a la duración de ese
    período, no puede excluirse la posibilidad de su transporte a larga
    distancia.

         Las parafinas cloradas no son fácilmente biodegradables.  Las de
    cadena carbonada corta con un contenido de cloro inferior al 50%
    parecen ser degradables en condiciones aeróbicas con microorganismos
    aclimatados, mientras que la degradación parece estar inhibida cuando
    el contenido de cloro es superior al 58%.  Las de cadenas carbonadas
    media y larga se degradan más lentamente.

         Las parafinas cloradas se bioacumulan en los organismos
    acuáticos, habiéndose comunicado factores de bioconcentración que
    oscilan entre 7 y 7155 en el caso de peces y entre 223 y 138 000 en el
    de mejillones.  En los peces, las de cadena corta experimentan mayor
    acumulación que las de cadenas media y larga.  Se ha observado
    radioactividad principalmente en la bilis, el intestino, el hígado, la
    grasa y las agallas después de la administración de parafinas cloradas
    marcadas con radioisótopos.  La absorción de las parafinas cloradas
    parece ser más eficiente en el caso de las que tienen menor contenido
    de cloro; la tasa de eliminación es más lenta en el caso de aquellas
    que tienen un elevado contenido de cloro.  La retención en los tejidos
    ricos en grasa parece aumentar a medida que aumenta el grado de
    cloración.

    4.  Concentración en el medio ambiente y exposición del ser humano

         Se cuenta con poca información sobre la concentración de las
    parafinas cloradas en el medio ambiente. Se han detectado
    concentraciones inferiores a 4 µg/litro en muestras de agua de
    mar en el Reino Unido.  En aguas no marítimas, se ha informado de
    concentraciones de 6 µg/litro en el Reino Unido; en Alemania, las
    concentraciones determinadas en 1994 oscilaban entre 0,08 y
    0,28 µg/litro.  En los Estados Unidos, si bien las concentraciones en
    el agua eran generalmente inferiores a 0,03 µg/litro, se observaron
    concentraciones superiores a 1,0 µg/litro en una pequeña proporción
    (1,2%) de las muestras.  En los sedimentos marinos, se tiene noticias
    de concentraciones de hasta 600 µg/kg de peso húmedo, y en sedimentos
    no marinos en el Reino Unido las concentraciones han alcanzado hasta
    15 000 µg/kg en regiones industrializadas y 1000 µg/kg en zonas
    alejadas de la industria.  En los sedimentos en un embalse de
    confinamiento de una planta de fabricación de parafinas cloradas en
    los Estados Unidos, las concentraciones registradas llegaron a
    alcanzar 170 000 µg/kg peso seco de PC de cadena larga, 50 000 µg/kg
    de PC de cadena media y 40 000 µg/kg de PC de cadena corta.  En
    Alemania, se han comunicado en 1994 concentraciones de hasta 83 µg/kg
    de peso seco de C10-13 y de hasta 370 µg/kg de peso seco de C14-17 en
    sedimentos.  En el Japón, las concentraciones en el sedimento han
    llegado a alcanzar 8500 µg/kg.

         Se han detectado parafinas cloradas en diferentes organismos. 
    Se han encontrado en los mamíferos terrestres en Suecia en
    concentraciones que oscilan entre 32 y 88 µg/kg de tejido (140 a
    4400 µg/kg de lípidos).  Sin embargo, no se detectaron en ovejas que

    pastaban en zonas alejadas de la producción de parafinas cloradas en
    el Reino Unido.  Por lo que respecta a las aves, en el Reino Unido se
    observaron concentraciones que llegaron a alcanzar los 1500 µg/kg; en
    cuanto a los peces, se han comunicado concentraciones de hasta
    200 µg/kg en Suecia y el Reino Unido.  En los mejillones recogidos
    en los Estados Unidos y el Reino Unido, se tiene noticias de
    concentraciones que se han elevado a 400 µg/kg.  Con todo, en
    mejillones capturados en las cercanías de un punto de descarga de
    efluentes de una fábrica de parafinas cloradas se han registrado
    concentraciones de C10-20 que han alcanzado 12 000 µg/kg. En
    estudios post mortem se han detectado también PC en los tejidos
    humanos: en el tejido adiposo (concentración media de 100 a 190 µg/kg),
    los riñones (concentración media inferior a 90 µg/kg) y el hígado
    (concentración media inferior a 90 µg/kg).  En un estudio limitado, se
    detectaron concentraciones de hasta 500 µg/kg de parafinas cloradas, 
    principalmente C10-20, en un 70% de las muestras de diversos
    productos alimenticios.

         Se dispone de escasa información sobre la exposición ocupacional
    a las parafinas cloradas.  Se han observado niveles muy bajos de
    exposición a los aerosoles de PC de cadena corta (0,003 a 1,2 mg/m3)
    asociados con su uso en fluidos para el laboreo de metales, aunque no
    existe información disponible sobre la proporción que se puede
    inhalar.  Sobre la base de modelos matemáticos de la exposición sin
    medidas de control, se estimaron niveles elevados de contactos
    dérmicos (5 a 15 mg/cm2 al día) por lo que respecta a los fluidos
    especiales para labrado de metales que contienen concentraciones muy
    elevadas de PC de cadena corta, aunque cabe esperar que la absorción
    sea baja.  Las medidas de control permitirían reducir la exposición
    dérmica.

    5.  Cinética y metabolismo

         Se ha estudiado la toxicocinética de las parafinas cloradas en
    animales experimentales.  No se cuenta con información adecuada por lo
    que respecta a los seres humanos.  No se han realizado suficientes
    investigaciones sobre las posibles diferencias en materia de
    toxicocinética como consecuencia de las diferencias en la longitud de
    las cadenas.  Si bien se desconoce el grado de absorción de las PC
    después de su administración oral, éste parece disminuir a medida que
    aumenta la longitud de la cadena y el grado de cloración.  Según cuál
    sea la longitud de la cadena, puede producirse también absorción
    percutánea, aunque en un grado limitado (inferior al 1% de una dosis
    tópica de C18).  No se cuenta con datos sobre la absorción en el
    pulmón.

         La distribución de las parafinas cloradas ocurre principalmente
    en el hígado, los riñones, el intestino, la médula espinal, el tejido
    adiposo y los ovarios. Aunque no existe suficiente información en lo
    que respecta a la retención, un grado bajo de cloración podría

    aumentar el tiempo de retención al ser más lenta la redistribución.
    Se ha observado la presencia de PC, o de sus metabolitos, en el
    sistema nervioso central hasta 30 días después de su administración. 
    Podrían cruzar la barrera hemato-placentaria.  Si bien no se cuenta
    con información adecuada sobre las vías del metabolismo de las PC, en
    los estudios con radioisótopos se ha identificado el CO2 como
    producto final.

         Las parafinas cloradas pueden excretarse por vía renal, biliar y
    pulmonar (como CO2). Resulta difícil establecer el grado relativo de
    excreción por las diferentes rutas debido a la gran variabilidad de
    los diferentes estudios.  La total eliminación de esas sustancias
    disminuye a medida que aumenta el contenido de cloro, y los compuestos
    con elevado grado de cloración se excretan principalmente (más del
    50%) en forma de CO2.  Las PC pueden ser excretadas en la leche.

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

         Las parafinas cloradas de cadenas de diferentes longitudes
    presentan reducida toxicidad oral aguda.  Los efectos tóxicos como,
    por ejemplo, incoordinación muscular y piloerección resultaban más
    ostensibles después de una exposición aislada a parafinas cloradas de
    cadena corta.  Sobre la base de información muy limitada, la toxicidad
    aguda por inhalación y por contacto cutáneo parece ser también baja. 
    Se ha observado ligera irritación de la piel y de los ojos después de
    la aplicación de PC de cadena media (irritación cutánea).  Los
    resultados de varios estudios indican que las PC de cadena corta no
    provocan sensibilización cutánea.

         En estudios de toxicidad con dosis repetidas por vía oral, los
    órganos en que se manifiesta principalmente la toxicidad de las PC son
    el hígado, los riñones y la tiroides.  Por lo que respecta a los
    compuestos de cadena corta, se han registrado aumentos en el peso del
    hígado con las dosis más reducidas (en las ratas, el nivel más bajo de
    efecto observado es de 50 a 100 mg/kg peso corporal por día, y la
    concentración sin efectos observados es de 10 mg/kg de peso corporal
    al día).  Con posologías superiores, se han registrado también
    aumentos en la actividad de las enzimas hepáticas, proliferación
    del retículo endoplasmático liso y peroxisomas, síntesis de ADN
    replicante, hipertrofia, hiperplasia y necrosis del hígado.  Asimismo,
    se han observado disminución en el aumento del peso corporal
    (125 mg/kg de peso corporal por día en los ratones), aumentos del peso
    de los riñones (100 mg/kg de peso corporal por día en las ratas),
    síntesis de ADN replicante en las células renales (313 mg/kg de peso
    corporal por día) y nefrosis (625 mg/kg de peso corporal por día en
    las ratas).  Se han comunicado aumentos en el peso de la tiroides, e
    hipertrofia e hiperplasia de la tiroides (nivel más bajo de efecto
    observado de 100 mg/kg de peso corporal por día en las ratas) y
    síntesis de ADN replicante en las células foliculares de la tiroides

    (nivel más bajo de efecto observado de 313 mg/kg de peso corporal por
    día).  Con posologías superiores (1000 mg/kg de peso corporal por
    día), la función tiroidea se ve afectada, lo que se puede establecer
    por las concentraciones de tiroxina plasmática libre y total y la
    mayor concentración plasmática de la hormona tirotrófica en las ratas.

         En cuanto a los compuestos de cadena media, el efecto observado
    con las dosis más bajas es generalmente el aumento del peso del hígado
    y los riñones (nivel más bajo de efecto observado en las ratas de
    100 mg/kg de peso corporal al día; nivel sin efecto nocivo observado en
    las ratas de 10 mg/kg de peso corporal al día).  En estudios con ratas
    hembras, se han señalado aumentos en el colesterol sérico y cambios
    histológicos "ligeros, adaptativos" en la tiroides cuando se emplean
    posologías similares (nivel sin efecto nocivo observado de 4 mg/kg de
    peso corporal al día).

         Por lo que respecta a los compuestos de cadena larga, los efectos
    observados en ratas hembras con las posologías más bajas son hepatitis
    granulomatosa multifocal y aumento del peso del hígado (nivel más bajo
    de efecto nocivo observado de 100 mg/kg de peso corporal al día).

         En el único estudio sobre reproducción descrito, no se informó de
    efectos reproductivos adversos después de la exposición de las ratas a
    una PC de cadena media con 52% de cloro.  Con todo, la supervivencia y
    los pesos corporales de los hijuelos expuestos se redujo (el nivel más
    bajo de efecto observado para una disminución no significativa del
    peso corporal fue de 5,7 a 7,2 mg/kg de peso corporal por día; el
    nivel más bajo de efecto nocivo observado para menor supervivencia
    estuvo entre 60 y 70 mg/kg de peso corporal por día).  En un número
    limitado de estudios sobre los efectos de las PC de cadena corta,
    media y larga sobre el desarrollo de las camadas de las ratas, se
    registraron efectos adversos sólo en el caso de los compuestos de
    cadena corta, con dosis tóxicas para las madres (2000 mg/kg de peso
    corporal por día).  En cuanto a los compuestos de cadena media y
    larga, no se observaron efectos en la prole, incluso con posologías
    muy elevadas (1000 a 5000 mg/kg de peso corporal por día).

         Las parafinas cloradas no parecen inducir mutaciones en las
    bacterias.  Sin embargo, en las células de los mamíferos hay indicios
    de un bajo potencial clastógeno  in vitro pero no  in vivo.  También
    se tiene noticia de que las PC provocan transformación celular  in
     vitro.

         Se han llevado a cabo estudios de carcinogenicidad a largo plazo
    con ratas y ratones alimentados por sonda empleando una PC de cadena
    corta (C12; 58% de Cl) y una PC de cadena larga (C23; 43% de Cl).  En
    el caso de los ratones B6C3F1 expuestos al compuesto de cadena corta,
    se registraron aumentos en la incidencia de tumores hepáticos en los
    machos y las hembras, así como tumores de la glándula tiroides en las
    hembras.  En las ratas Fischer-344 expuestas al compuesto de cadena

    corta, se observó un mayor número de tumores hepáticos en los machos y
    las hembras, tumores renales (adenomas o adenocarcinomas) en los
    machos, tumores de la tiroides en las hembras y leucemias de las
    células mononucleares en los machos.  Por lo que respecta a las PC de
    cadena larga, se vio aumentada la incidencia de linfomas malignos en
    ratones machos y de tumores de la glándula adrenal en las ratas
    hembra.

    7.  Efectos en el ser humano

         A pesar del uso muy difundido de las parafinas cloradas, no hay
    informes de casos de irritación o de sensibilización dérmica.  Esto se
    ve corroborado por los resultados de un número limitado de estudios
    realizados con voluntarios en los que las PC provocaron mínima
    irritación dérmica, pero no sensibilización.

         No se dispone de datos sobre otros efectos de las PC en el ser
    humano.

    8.  Efectos en otros organismos en laboratorio y sobre el terreno

         Se ha demostrado que las parafinas cloradas de cadena corta son
    sumamente tóxicas para los invertebrados acuáticos, tanto de agua
    dulce como de mar, oscilando los valores de CL50-CE50 entre 14 y
    530 µg/litro.  La mayoría de las pruebas de toxicidad aguda para los
    invertebrados acuáticos con parafinas cloradas de cadena media y larga
    son superiores a la solubilidad en agua.  Sin embargo, en un estudio
    realizado con crustáceos  Daphnia con una PC de cadena media se
    observó toxicidad aguda con una CE50 de 37 µg/litro.  En el caso de
    los peces, las PC de cadena corta, media y larga parecen tener poca
    toxicidad aguda, con valores de CL50 muy superiores a la solubilidad
    en agua.

         Las parafinas cloradas de cadena corta presentan toxicidad a
    largo plazo a las algas, los invertebrados acuáticos y los peces
    con concentraciones tan bajas como 19,6, 8,9 y 3,1 µg/litro,
    respectivamente; en cuanto a las especies más sensibles estudiadas,
    las concentraciones sin efecto observado parecen oscilar entre 2 y
    5 µg/litro.  Un producto de cadena media y otro de cadena larga
    tuvieron efectos crónicos en crustáceos  Daphnia con concentraciones
    de 20 a 35 µg/litro y de < 1,2 a 8 µg/litro, respectivamente.  La
    toxicidad a largo plazo parece ser baja en el caso de los peces.  No
    se cuenta con datos sobre las algas.

         Atendiendo a los limitados datos disponibles, la toxicidad aguda
    de las PC en las aves es baja.

    9.  Evaluación de los riesgos para la salud de los seres humanos y de
        los efectos sobre el medio ambiente

         Los alimentos son probablemente la fuente principal de exposición
    de la población general. Sobre la base de los datos limitados sobre
    las concentraciones presentes en los alimentos, las estimaciones más
    desfavorables del consumo diario en los productos lácteos y mejillones
    son de 4 y 25 µg/kg peso corporal por día, respectivamente.  En
    general, se calcula que la cantidad de PC ingeridas diariamente es
    inferior al límite tolerable por lo que respecta a los efectos no
    neoplásicos, o a los valores recomendados en cuanto a los efectos
    neoplásicos (compuestos de cadena corta).

         Siempre que se sigan procedimientos adecuados de higiene y
    seguridad personal, cabe esperar que el riesgo para la salud de los
    trabajadores expuestos a las PC sea mínimo.

         La información disponible indica que las parafinas cloradas
    son bioacumulativas y persistentes.  Los datos sobre los niveles
    ambientales de las de cadena corta indican que en áreas cercanas a las
    fuentes de descarga existe riesgo para los organismos, tanto de agua
    dulce como estuarinos.  Asimismo, las de cadena media y larga pueden
    presentar riesgos para los invertebrados acuáticos.

         El enriquecimiento de las parafinas cloradas en los sedimentos,
    sus posibilidades de reabsorción y su toxicidad en medio acuático son
    indicios de posible riesgo para los organismos que habitan en los
    sedimentos.