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

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

    World Health Organization
    Geneva, 1982

        The International Programme on Chemical Safety (IPCS) is a joint
    venture of the United Nations Environment Programme, the International
    Labour Organisation, and the World Health Organization. The main
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    with chemical accidents, coordination of laboratory testing and
    epidemiological studies, and promotion of research on the mechanisms
    of the biological action of chemicals.

    ISBN 92 4 154080 X

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         1.1. Summary
               1.1.1. Properties and analytical methods
                Analytical methods
               1.1.2. Sources of environmental pollution
               1.1.3. Environmental concentrations and levels of exposure
                General population exposure
                Occupational exposure
               1.1.4. Effects on experimental animals
               1.1.5. Clinical and epidemiological studies in man
               1.1.6. Evaluation of health risks
               1.1.7. Control measures
         1.2. Recommendations for further studies
               1.2.1. Analytical aspects
               1.2.2. Sources and levels in the environment
               1.2.3. Studies on experimental animals
               1.2.4. Human studies

         2.1. Properties and analytical methods
               2.1.1. Chemical composition and properties
               2.1.2. Methods of sampling and analysis
                Gases and vapours
         2.2. Sources of environmental pollution
               2.2.1. Natural occurrence
               2.2.2. Man-made sources
                Disposal of waste
         2.3. Toxicological effects of crude oils
               2.3.1. Effects on experimental animals
               2.3.2. Effects on man

         3.1. Properties and analytical methods
               3.1.1. Chemical composition and properties
                Special boiling point solvents (SBPs)
                White spirits
                High boiling aromatic solvents
               3.1.2. Purity of petroleum solvents
               3.1.3. Methods of sampling and analysis

         3.2. Sources of environmental pollution
               3.2.1. Natural occurrence
               3.2.2. Man-made sources
         3.3. Environmental exposure levels
         3.4. Environmental distribution and transformation
         3.5. Metabolism
               3.5.1. Absorption
               3.5.2. Distribution in the body
               3.5.3. Biotransformation
               3.5.4. Elimination
         3.6. Effects on experimental animals
               3.6.1. Short-term exposure
               3.6.2. Long-term exposure
               3.6.3. Mutagenicity, teratogenicity, and carcinogenicity
         3.7. Effects on man
               3.7.1. Controlled exposures
                Effects of dermal exposure
                Effects of inhalation
               3.7.2. Epidemiological studies
                Occupational exposure
                General population exposure
               3.7.3. Clinical studies
                Effects of dermal exposure
                Effects of inhalation
                Effects of ingestion

         4.1. Properties and analytical methods
               4.1.1. Chemical and physical properties
                Purity of product
               4.1.2. Methods of sampling and analysis
         4.2. Sources of environmental pollution
               4.2.1. Natural occurrence
               4.2.2. Man-made sources
                Disposal of waste
         4.3. Environmental exposure levels
         4.4. Environmental distribution and transformation
         4.5. Metabolism
         4.6. Effects on experimental animals
               4.6.1. Short-term exposure
                Effects of dermal exposure

               4.6.2. Long-term exposure
                Carcinogenic effects
                Effects of dermal exposure and
                                 subcutaneous administration
                Effects of inhalation and intratracheal
                Dietary studies
         4.7. Effects on man
               4.7.1. Occupational exposure
                Skin disorders
                Skin carcinogenicity
                Effects of off mist exposure
         4.8. Clinical studies

    5. BITUMEN
         5.1. Properties and analytical methods
               5.1.1. Chemical and physical properties
               5.1.2. Methods of sampling and analysis
         5.2. Sources of environmental pollution
               5.2.1. Natural sources
               5.2.2. Man-made sources
         5.3. Environmental exposure levels
         5.4. Environmental distribution and transformation
         5.5. Metabolism
         5.6. Effects on experimental animals
               5.6.1. Short-term exposure
               5.6.2. Long-term exposure
         5.7. Effects on man
               5.7.1. Epidemiological studies
                Occupational exposure
                General population exposure
                High (accidental) exposure
               5.7.2. Clinical studies

         6.1. Crude oils
         6.2. Petroleum solvents
         6.3. Lubricating base oils, greases, and waxes
         6.4. Bitumen

         7.1. General
         7.2. Petroleum solvents
         7.3. Lubricating base oils, greases, and waxes
         7.4. Bitumen



        While every effort has been made to present information in the
    criteria documents as accurately as possible without unduly delaying
    theft publication, mistakes might have occurred and are likely to
    occur in the future. In the interest of all users of the environmental
    health criteria documents, readers are kindly requested to communicate
    any errors found to the Division of Environmental Health, World Health
    Organization, Geneva, Switzerland, in order that they may be included
    in corrigenda which will appear in subsequent volumes.

        In addition, experts in any particular field dealt with in the
    criteria documents are kindly requested to make available to the WHO
    Secretariat any important published information that may have
    inadvertently been omitted and which may change the evaluation of
    health risks from exposure to the environmental agent under
    examination, so that the information may be considered in the event of
    updating and re-evaluation of the conclusions contained in the
    criteria documents.



    Dr D. A. Akintonwa, Department of Biochemistry, Faculty of Medicine,
         University of Calabar, Calabar, Nigeria

    Dr L. Boniforti, Department of Contaminants, Laboratory of Toxicology,
         Institute of Health, Rome, Italy

    Dr K. W. Jager, Shell Internationale Research, Maatschappij B.V., The
         Hague, Netherlands  (Rapporteur)

    Professor L. Jirásek, 1st Dermatological Clinic, Charles University,
         Prague, Czechoslovakia

    Professor A. A. Kasparov, Institute of Industrial Hygiene and
         Occupational Diseases, Academy of Medical Sciences, Moscow, USSR

    Professor W. O. Phoon, Department of Social Medicine and Public
         Health, Faculty of Medicine, University of Singapore, Singapore

    Dr M. Rouhani, Institute of Occupational Safety and Health, Ministry
         of Labour and Social Affairs, Teheran, Iran (Present address:
         Nice, France)

    Dr E. Schmidt, Directorate of Malariology and Environmental
         Sanitation, Ministry of Health and Welfare, Caracas, Venezuela

    Dr N. K. Weaver, American Petroleum Institute, Washington DC, USA

     Representatives of other organizations

    Dr P. V. C. Pinnagoda, International Labour Organisation, Geneva,

    Professor L. Parmeggiani, Permanent Commission and International
         Association on Occupational Health

    Dr J. W. Huismans, International Register of Potentially Toxic
         Chemicals, United Nations Environment Programme, Geneva,

    Mr J. Wilbourn, International Agency for Research on Cancer, Lyons,


    Dr A. David, Medical Officer, Office of Occupational Health, World
         Health Organization, Geneva, Switzerland  (Co-Secretary)

    Dr M. A. El Batawi, Chief Medical Officer, Office of Occupational
         Health, World Health Organization, Geneva, Switzerland

    Mrs B. Goelzer, Scientist, Office of Occupational Health, World Health
         Organization, Geneva, Switzerland  (Co-Secretary)

    Dr Y. Hasegawa, Medical Officer, Environmental Health Criteria and
         Standards, World Health Organization, Geneva, Switzerland

    Dr M. Sharratt, Senior Toxicologist, BP Group Occupational Health
         Centre, Middlesex, England  (Temporary Adviser)


        Further to the recommendations of the Stockholm United Nations
    Conference on the Human Environment in 1972, and in response to a
    number of World Health Assembly Resolutions and the recommendation of
    the Governing Council of the United Nations Environment Programme, a
    programme on the integrated assessment of the health effects of
    environmental pollution was initiated in 1973. The programme, known as
    the WHO Environmental Health Criteria Programme, has been implemented
    with the support of the Environment Fund of the United Nations
    Environment Programme. In 1980, the Environmental Health Criteria
    Programme was incorporated into the International Programme on
    Chemical Safety. The result of the Environmental Health Criteria
    Programme is a series of criteria documents.

        The Office of Occupational Health, WHO, was the unit responsible
    for the development of the Environmental Health Criteria document on
    Selected Petroleum Products.

        The Task Group for this document met in Geneva from 15-19 October
    1979. The meeting was opened by Dr M. A. El Batawi, Chief, Office of
    Occupational Health, who welcomed the participants and the
    representatives of other international organizations on behalf of the

        The Task Group reviewed and revised the second draft criteria
    document and made an evaluation of the health risks of exposure to
    selected petroleum products.

        The first and second drafts were prepared by Dr K. W. Jager,
    Shell Internationale Research, Maatschappij B. V., The Hague,
    Netherlands. Comments on the second draft, which have been
    incorporated in this report, were received from the national focal
    points for the WHO Environmental Health Criteria Programme in
    Australia, the Federal Republic of Germany, Mexico, the United
    Kingdom, and the USA, and from the WHO Collaborating Centres of
    Occupational Health in: Chile, Finland, Indonesia, Netherlands,
    Singapore, Sweden, Switzerland, the United Kingdom, and the USSR.
    Additional comments were received from Dr. R. E. Eckardt (USA), Dr M.
    Rouhani (Iran), from the International Petroleum Industry
    Environmental Conservation Association, and from the American
    Petroleum Institute.

        The collaboration of these national institutions, international
    organizations, and individual experts is gratefully acknowledged. The
    Secretariat also wishes to thank Dr K. W. Jager and Dr M. Sharratt for
    their invaluable assistance in the final stages of the preparation of
    the document.

        As the final text of the evaluation could not be distributed at
    the meeting, it was circulated to all participants in November 1978.
    The comments received were then considered by the Rapporteur and some
    members of the Secretariat, and suggested alterations were included.
    Later, section 2.1.2, Methods of sampling and analysis, was completely
    rewritten by Mr. T. P. C. M. van Dongen of the Shell Laboratory
    (Amsterdam) and Dr K. W. Jager, the Rapporteur.

        The document has been based, primarily, on original publications
    listed in the reference section. However, several recent reviews of
    health aspects of petroleum products have also been used, including:
    Petroleum Handbook (1966); API Toxicology Reviews (API, 1965, 1967,
    1969); US DHEW (1970); and Lazarev & Levina (1976).

        The purpose of this document is to review and evaluate available
    information on the biological effects of some petroleum products, and
    to provide a scientific basis for decisions aimed at the protection of
    human health from the adverse consequences of exposure to these
    substances in both the occupational and general environments.

        It was only feasible to discuss several groups of related
    products, and to select priorities among them. Thus, non-fuel products
    derived from crude oils are considered in three broad groups, i.e.,
    petroleum solvents, lubricating base-oils, and bitumens. These have
    been selected as priorities, because of their widespread use and
    because large sub-groups of the population may come into close contact
    with them through occupational or domestic use. Moreover, adverse
    health effects are known to occur from occupational exposure to some
    of these products.

        Base chemicals derived from the cracking of crude oil fractions,
    such as ethylene, propylene, and other olefins, and fuels derived from
    crude oils ranging from gasoline to heavy fuel oil, are not discussed
    in this document. As fuels and non-fuels of a similar boiling range
    may have similar effects, e.g., on the skin or, after aspiration, on
    the respiratory tract, most toxicological data discussed in this
    review are more or less relevant to crude oil-derived fuels of a
    similar boiling range. In fact, it is impossible to make a strict
    division between data relating to fuels and non-fuels and they have
    been considered together, whenever relevant.

        The published literature and other available information have
    been critically evaluated and where possible, an attempt has been made
    to establish whether or not, under certain conditions, a potential
    risk to man exists. Suggestions for avoiding established risks and for
    further studies have also been made.

        The environmental impact, if any, of the products has only been
    considered where it is directly related to the health of man.

        Details of the WHO Environmental Health Criteria Programme
    including some terms frequently used in the document may be found in
    the general introduction to the Environmental Health Criteria
    Programme published together with the environmental health criteria
    document on mercury (Environmental Health Criteria 1, Mercury, Geneva,
    World Health Organization, 1976), now also available as a reprint.

        Financial support for the publication of this criteria document
    was kindly provided by the United States Department of Health and
    Human Services through a contract from the National Institute of
    Environmental Health Sciences, Research Triangle Park, North Carolina,
    USA -- a WHO Collaborating Centre for Environmental Health Effects.

        The following conversion factors have been used in the present

    benzene   1 ppm = 3.0 mg/m3

    gasoline  1 ppm = 4.5 mg/m3a

    heptane   1 ppm = 4.0 mg/m3

    hexane    1 ppm = 3.6 mg/m3

    octane    1 ppm = 4.85 mg/m3

    pentane   1 ppm = 3.0 mg/m3

    toluene   1 ppm = 3.75 mg/m3

    xylene    1 ppm = 4.35 mg/m3


    a  A conversion factor for gasoline of 1 ppm = 4.5 mg/m3 has been
       used throughout the document, though this factor normally varies
       according to the composition of the gasoline.


    1.1  Summary

    1.1.1  Properties and analytical methods  Properties

         (a) Crude oils are a complex mixture of straight and branched
    chain paraffinic,  cycloparaffinic, aromatic and polynuclear aromatic
    hydrocarbons together with small amounts of sulfur and nitrogen
    compounds. The composition of crude oils varies considerably with
    geographical origin. They can be broadly divided into paraffinic,
    asphaltic, and mixed crude oils. Paraffinic crude oils provide large
    amounts of paraffinic hydrocarbons, paraffin wax, and high grade oils,
    while asphaltic crude oils province more cycloparaffins and high
    viscosity lubricating oils.

         (b) Petroleum solvents, produced by the distillation of crude
    oils, are also complex mixtures of hydrocarbons. They are generally
    classified on the basis of distillation ranges. Special boiling-point
    solvents, such as petroleum ether and rubber solvent, are mixtures of
    C-5 to C-9 normal- and branched-chain paraffins and cycloparaffins
    with a boiling-range of 30-160°C. With solvents such as Stoddard
    solvent, mineral spirits, and low aromatic white spirits, the chain
    lengths are longer (C-7 to C-12) and the boiling-range higher
    (150-220°C) and they contain various amounts of aromatic compounds.
    Higher boiling-point solvents (B.P. 160-300°C) containing more than 9
    carbon atoms per molecule are also produced.

         (c) Lubricant base oils, greases, and waxes are products with
    boiling-points in the range of 300-700°C that are normally produced by
    high-vacuum distillation of the residues of the initial distillation.

         (d) Bitumen, the solid and semi-solid residue of the
    distillation process, varies from a highly viscous liquid to a brittle
    solid, at ambient temperatures, and consists of a mixture of
    asphaltenes (high relative molecular mass aromatic and heterocyclic
    hydrocarbons), resins (polymers formed from unsaturated hydrocarbons
    during processing), together with saturated hydrocarbons and aromatic
    hydrocarbons containing one or more benzene rings per molecule
    (including polynuclear aromatic hydrocarbons).  Analytical methods

        A vast and specialized literature on sampling methods and
    analytical techniques is available for petroleum products. Many
    techniques have proved useful, e.g., infrared spectroscopy, thin-layer
    chromatography, ultraviolet fluorescent spectrometry, capillary
    gaschromatography, and chromatography combined with mass spectrometry.

    1.1.2  Sources of environmental pollution

         (a) Crude oil is normally transported in large volumes in
    tankers and pipelines. Breakdown or leakage of these may cause a major
    and sudden environmental hazard. Less significant degrees of pollution
    have resulted from the cleaning out of oil tankers. Certain volatile
    components, especially hydrogen sulfide but also other sulfur
    compounds, acids, and hydrocarbons may contaminate the atmosphere near
    oilfields and refineries.

         (b) As a rule, petroleum solvents do not present serious
    pollution problems for the general population, since they are mainly
    used in industry and seldom domestically. Spillage or use in poorly
    ventilated rooms or without proper control measures may cause serious
    work-place pollution. Solvents containing  n-hexane or benzene may
    present particular hazards with respect to health.

         (c) Because of theft nature and uses, lubricating base oils,
    greases, and waxes rarely present problems for the general population
    though spillage may create localized environmental problems. However,
    in industry, some of these products, especially the metal working
    oils, may produce marked contamination of the workplace and equipment.

         (d) From the available evidence, it appears that bitumen is not
    a significant source of environmental pollution but, under certain
    conditions, occupational exposure may occur.

    1.1.3  Environmental concentrations and levels of exposure  General population exposure

        Little information is available concerning the concentrations of
    petroleum products in air, water, or food. Most of the crude oils are
    produced from deep wells, but natural seepage occurs on land and on
    the sea-bed. Natural bitumen and asphalt deposits occur in several
    parts of the world. There are not sufficient data available to
    estimate the total environmental exposure of human beings to these
    petroleum products. On occasions, the general population may be
    exposed for short periods to fumes from heated bitumen used in road
    building or roofing. Small amounts of hydrocarbons, probably derived
    from petroleum hydrocarbons, have been found in shell fish. Volatile
    petroleum components may contribute to atmospheric pollution near
    refineries, and storage and pumping areas.  Occupational exposure

         (a) Crude oil is usually handled in closed systems from oil
    well to refinery, so that workers are not exposed to it, unless a
    serious breakdown or leakage occurs. However, volatile components can
    escape at well heads, pump glands, or through vents in storage tanks
    and tanks on ships.

         (b) Petroleum solvents are extensively manufactured and are
    widely used in many occupations. Because of their volatility,
    industrial exposure to "special-boiling-point" spirits can sometimes
    be high. Excessive exposure has occurred and has caused ill health in
    workshops where ventilation was insufficient. With white spirits, skin
    contact is usually of greater importance than inhalation, at least at
    ambient temperatures. Skin contact is particularly important in
    relation to high aromatic solvents, since the aromatic moieties tend
    to penetrate skin readily. Both skin contact and exposure to fumes or
    mists of high boiling-point aromatic solvents can occur

         (c) The extent of occupational exposure to lubricating oils,
    greases, and waxes depends on the occupation and on the precautions
    adopted. Some lubricants and transformer oils are handled only
    occasionally, while work with automatic lathes of old design can
    result not only in direct contamination of clothes and exposed skin,
    but also in the inhalation of oil mist that may be produced by the
    machine and will further contaminate the skin and clothing. Moreover,
    other equipment, floors, and even roofs may become contaminated.

         (d) Extensive exposure to bitumen may occur in such occupations
    as roadbuilding and repairing, roofing, and flooring.

    1.1.4  Effects on experimental animals

    (a) Crude oil

        Toxicological studies on mice and rabbits have shown that, in
    general, the tumorogenicity of crude oils is lower than that of some
    distilled fractions.

    (b) Petroleum solvents

        The few data available suggest that solvents are readily absorbed
    when inhaled or ingested and that excretion is also rapid. The
    metabolic products of benzene and  n-hexane are well established but
    the metabolism of other petroleum solvents is not well documented.

        Animal studies have been complicated by the fact that mixtures
    have generally been studied and that the composition of superficially
    similar products can vary greatly. However, studies on representative
    samples have demonstrated that solvents present a low oral and
    percutaneous hazard for rats. Skin is severely damaged only on
    prolonged, repeated contact; "short-chain" solvents mainly have a
    defatting action, while dermatotoxic effects are found with

    "longer-chain" solvents. In general, the higher the aromatic content
    of the solvents, the more intense the effects, whatever the route of
    exposure. In short-term exposure (4-8 h) of rats, atmospheric
    concentrations causing the death of 50% of animals (LC50) ranged
    mainly from approximately 1000-15 000 ppm. The main signs of poisoning
    were respiratory tract irritation, depression of the central nervous
    system (CNS), and coma, followed rapidly by death.

        The presence of small volumes of solvent in the respiratory tract
    led to chemical pneumonitis in all species tested. The degree of
    injury depended on the viscosity rather than on the chemical nature of
    the materials; the higher the viscosity, the lower the possibility of
    aspiration into the deeper parts of the lungs.

        Repeated exposure of rats, cats, and dogs to the vapours of a
    wide range of petroleum solvents showed that the toxicity was
    consistently low. However, exposure to  n-hexane resulted in
    pathological changes similar to those associated with peripheral
    neuropathy in man. The maximum no-observed-adverse-effect level for
     n-hexane is not yet certain. Results of teratogenicity studies on a
    wide range of hydrocarbon solvents have been essentially negative.

        Benzene and the aromatic extracts are the only well-defined
    petroleum solvents for which carcinogenicity has been reported.

    (c) Lubricating base oils, greases, and waxes

        These substances are of low acute oral and dermal toxicity,
    though high oral doses have a laxative effect.

        In long-term studies on mice, rats, guineapigs, and rabbits, it
    has been demonstrated that the carcinogenic activity of these products
    resides in the polynuclear aromatic hydrocarbon fraction. By suitable
    refining, oils, greases, and waxes can be obtained that consistently
    give negative results in skin-painting tests. The most potentially
    carcinogenic substances have been found among the 4,5, and 6 condensed
    ring polynuclear compounds with relative molecular masses ranging from
    230 to 330. Experimental evidence suggests that some long-chain
    aliphatic, alicyclic, and alkylaromatic hydrocarbons may act as
    co-carcinogens, when applied to the skin together with the
    carcinogenic fraction.

        It has been shown that washing the skin of animals after
    application of carcinogenic oils decreases both the number and rate of
    appearance of tumours. The degree of reduction is related to the time
    between application and washing. A lowering of the frequency of
    application of the oils also reduces the rate of tumour development.

        Carcinogenic activity has been demonstrated in certain
    metal-working and textile oil formulations and there is evidence that
    carcinogenic polynuclear aromatic compounds may be produced, when oil
    products are subjected to high temperatures.

        Aspiration of oils has been shown to induce a foreign body
    reaction in animal lungs as well as lipid pneumonia. However, when
    animals were exposed to oil mist, very little was retained in the
    lungs, and lipid pneumonia did not occur, even at high exposure
    levels. From studies on the mouse, rat, hamster, rabbit, and dog, it
    would appear that atmospheric exposure to 5 mg/m3 of oil mist is
    without risk.

        Oral administration of food-grade mineral oils and waxes to rats
    did not result in any carcinogenic or chronic toxic effects.

    (d) Bitumens

        Although some bitumens applied to the skin of mice exhibit
    carcinogenic activity, it is low compared with that of coal tar, and
    it is generally accepted that the toxicity of bitumens is low.

    1.1.5  Clinical and epidemiological studies in man

    (a) Crude oils

        Many cases of keratotic changes and epithelioma on exposed parts
    of the skin have been reported in workers exposed to crude oils. The
    relative roles of the oil and of other factors, e.g., sunlight, is

    (b) Petroleum solvents

        Petroleum solvents with boiling-ranges up to 230°C are primary
    irritants, though their irritant and defatting actions decrease as the
    boiling-range increases. Solvents of naphthenic origin or with a high
    aromatic content tend to be the most irritant. On repeated contact,
    the keratin layer of the skin is damaged, making the skin more
    susceptible to other irritants, sensitizing agents, and bacteria.

        Acute occupational poisoning by gasoline vapour has usually been
    the result of entering unpurged gasoline tanks or other premises,
    where high concentrations of gasoline vapour have accumulated. With
    increasing concentrations of gasoline vapour, exposed subjects may
    experience drowsiness, dullness, numbness, and headache followed by
    dizziness, ataxia, and nausea. Exposure to higher concentrations of
    vapour, or for a longer period, may lead to loss of consciousness
    followed by death, which may be preceded by convulsions.

        In the last 15 years, an increasing number of cases of
    polyneuropathy have been reported in workers exposed to high
    concentrations of volatile petroleum solvents, mainly consisting of
    technical hexane. Though  n-hexane seems to play a major role, the
    possibility that other components of the solvents may have a similar
    or synergistic action cannot be ruled out.

        Ingestion of large volumes of solvent is usually well tolerated,
    unless aspiration occurs. Small volumes (1-2 ml) of kerosene will, if
    aspirated, cause acute chemical pneumonitis, which is often fatal. The
    prognosis of chemical aspiration pneumonitis has improved over the
    past years with improved methods of treatment. Where no aspiration
    occurs, the symptoms are similar to those following over-exposure to

        Long-term exposure to low vapour concentrations has been reported
    to produce non-specific symptoms such as nervousness, loss of
    appetite, and nausea. Other symptoms referable to the peripheral and
    central nervous systems, the gastrointestinal tract, the lungs, eyes,
    and reproductive system have also been described. No
    dose-concentration effect relationships can be derived from present
    knowledge either for short-term or long-term exposures. It is
    considered probable that blood abnormalities, previously reported
    following exposure to solvents, were, in fact, due to the presence of
    benzene in the solvents.

    (c) Lubricating oils, greases, and waxes

        Exposure of the skin to these products can induce several types
    of disorder including primary irritation, oil ache, hyperkeratosis,
    and photosensitivity. The degree of severity of these disorders
    depends on the nature of the oil, the integrity of skin, the frequency
    and length of contact, and individual susceptibility. In general,
    lower-boiling-point materials have a more pronounced defatting effect,
    while the higher-boiling-point materials induce the formation of acne.
    In many cases, additives or contaminants in the oils are responsible
    for the disorders, rather than the oil itself.

        Prolonged exposure to non-solvent, refined mineral oils has been
    associated with the induction of cancer of the scrotum, e.g., in
    machine operators and those involved in spinning operations. Less
    frequently, cancer at other sites, including the hand and forearm,
    lung, and bronchus have been associated with exposure to oils
    containing significant concentrations of polynuclear aromatic
    compounds. Results of epidemiological studies have suggested an
    association between exposure to oil mist and an increased incidence of
    pulmonary cancer. However, the exact levels of exposure to the oils
    and polynuclear aromatic compounds in these studies is not known. Very
    rarely, cases have been reported of lipid pneumonia associated with
    prolonged exposure to high concentrations of oil mist. Whether there
    was a causal relationship is uncertain.

    (d) Bitumen

        Evidence from epidemiological studies on workers in oil
    refineries, highway construction, roofing industries, and bitumen
    transport firms strongly suggests that petroleum-based bitumens do not
    present a significant health hazard.

        The possibility that bitumen and the vapours emanating from it
    might contribute to the overall incidence of cancer of the skin and of
    the respiratory tract has to be considered in view of their content of
    polynuclear aromatic compounds, but there are no data to substantiate

    1.1.6  Evaluation of health risks

        Available information indicates that the health risks for the
    general population from the production of crude oil and the
    manufacture and use of petroleum products are very low. Under normal
    circumstances, there is, at the most, a nuisance because of pollution
    of the air and/or water.

        The major risks are related to the health of workers involved in
    the manufacture or handling of these products.

        Exposure to high concentrations of the vapour of petroleum
    solvents can produce narcotic effects. Long-term exposures to low
    concentrations have been reported to produce non-specific symptoms.
    The no-observed-adverse-effect level of exposure has not been
    established for these products. Prolonged exposure to  n-hexane has
    resulted in the development of polyneuropathies most of which have
    proved reversible on cessation of exposure. In the case of solvents
    containing benzene, the possibility of bone marrow depression and
    leukaemogenesis must be borne in mind. Prolonged skin contact with
    petroleum solvents can lead to contact irritative dermatitis, but only
    rarely to contact allergic dermatitis.

        Both types of skin disease occur more frequently in professions
    using products derived from base oils, especially metal-working oils.
    Such diseases may cause considerable distress, they affect the general
    well-being and reduce the capacity to work. Skin cancer has been
    described in workers after prolonged and intensive exposure to less
    refined base oil derivatives, e.g., the metal-working oils formerly in
    use. Practically all these skin diseases appeared in occupations where
    hygiene and working conditions were poor. These factors were as
    important as the intrinsic toxicity of the oils.

        Exposure to low concentrations of mists of highly refined oils
    appears to be without serious health hazards; this is not necessarily
    the case with less refined oils, which have been reported to cause an
    increased incidence of cancer of the respiratory tract, after
    prolonged high-level exposure.

        There is no evidence to suggest that the production and use of
    bitumens presents a health hazard for the general population and for
    workers (other than burns from splashes of hot bitumen).

    1.1.7  Control measures

        Every effort should be made to avoid the contamination of
    workers, the workplace, or the general environment with petroleum
    products. This can be achieved by appropriate technological measures
    and good work practice.

        As far as possible, products containing highly toxic compounds
    should be avoided and alternatives sought.

        Where contact is unavoidable, suitable protective equipment
    should be used. Health education of employers and workers should be
    promoted emphasizing the necessity for maintaining high standards of
    personal hygiene. When necessary, pre-employment, and regular periodic
    medical examinations should be carried out on exposed workers.

        Adequate control programmes should be implemented, including the
    disposal of many types of waste oil products.

    1.2  Recommendations for further studies

    1.2.1  Analytical aspects

        A major problem in assessing the health hazards of petroleum
    products is that the majority have been developed and specified
    according to their physical properties such as the boiling-point and
    viscosity rather than their chemical composition. Products with the
    same physical properties may vary considerably in chemical composition
    (e.g., different proportions of isomers) and, hence, biological
    properties. It is, therefore, important for future experimental animal
    and human studies that analytical methods should be available to
    establish the chemical structure of the products to which subjects are
    exposed, and research into suitable methods should continue.
    Analytical methods suitable for determining low concentrations of
    solvents and oil products and their individual components in the
    environment should continue to be developed and some consideration
    should be given to the development of simple control techniques at the
    work-site level.

    1.2.2  Sources and levels in the environment

        In some cases, the use of aromatic extracts and highly aromatic
    base oils should be reconsidered and alternatives sought, where there
    might be a risk of carcinogenic effects on the skin and respiratory

        More information is needed on the concentrations of petroleum
    products and their constituents in the work-place and the general
    environment, especially in the neighbourhood of refineries and
    petrochemical plants. Such data would result in more meaningful
    epidemiological studies and would be of use in the development of
    suitable measures to control pollution and the exposure of the general

        There is a need to understand more fully the factors responsible
    for the production of oil mists and the importance to health of
    inhalation of particles of various sizes. Most oil mists contain
    chemical additives and the possible effects of these, when inhaled by
    man, must be considered.

        Improved methods for quantifying human exposure to petroleum
    products in the working environment are required. While inhalation
    exposure can be estimated from atmospheric monitoring, the extent of
    exposure through skin contact has rarely, if ever, been examined.

        International cooperation is needed in the elaboration and
    clarification of exposure limits for petroleum products and their
    components in water, air, and the working environment. These should be
    based on adequate evaluation of their risks.

    1.2.3  Studies on experimental animals

        More studies are needed of the mechanisms by which petroleum
    products produce injury in experimental animals. Little information is
    available on the metabolism and pharmacokinetics of the components of
    oils. In particular, elucidation of the dose/time/effect relationships
    of exposure of animals to  n-hexane would be of value in assessing
    acceptable human exposure levels. Information on the neurotoxicity of
    other components of petroleum solvents and on their ability to act
    synergistically with  n-hexane should also be sought. The possible
    effects of petroleum solvents on aspects of the reproductive
    processes, not already studied in depth, should be examined. A quick
    and reliable analytical method for determining 4, 5, and 6 condensed
    ring polynuclear aromatic compounds needs to be developed and its
    predictive value in assessing carcinogenic potential examined.
    Similarly, a short-term biological test for carcinogenicity,
    applicable to oil products, would be of great value in providing a
    method for the rapid assessment of the potential carcinogenicity of

    1.2.4  Human studies

        Further studies to determine the dose-effect relationships of
    exposure to a wide range of petroleum oil and solvent products would
    be of value, particularly in relation to long-term exposure. In such
    studies, the possibility that any adverse effect produced by exposure
    might be influenced by working conditions (e.g., general work
    environment, heat, stress, and noise) should be considered and, if
    necessary, investigated. As well as studying general health, possible
    specific actions on the cardiovascular, gastrointestinal, and central
    and peripheral nervous systems should be considered. Possible
    susceptible groups, and factors such as age, sex, state of health, and
    genetic background should also be taken into consideration. There is a
    need to assess the extent of health problems caused by the use of
    petroleum products in the developing countries, where exposure
    conditions may be less well controlled; relatively few studies
    relating to these problems have been carried out.

        Efforts should be made to develop common criteria for the
    detection and definition of health effects in order to allow
    comparison of findings between different research workers and
    institutes throughout the world.

    2.  CRUDE OILS

    2.1  Properties and Analytical Methods

    2.1.1  Chemical composition and properties

        Crude oils originate from the decomposition and transformation of
    aquatic, mainly marine, animals and plants that became buried under
    successive layers of mud and silt some 15-500 million years ago; they
    are essentially very complex mixtures of many thousands of different
    hydrocarbons. Depending on the source, the oils contain various
    proportions of straight and branched-chain paraffins, cycloparaffins,
    and naphthenic, aromatic, and polynuclear aromatic hydrocarbons. The
    younger oils are characterized by their more asphaltic nature. As many
    "paraffins" of high relative molecular mass may contain naphthenic
    and/or aromatic rings, this should not be understood as a sharp
    division between defined chemical entities.

        The hydrocarbons may be gaseous, liquid, or solid, under normal
    conditions of temperature and pressure, depending on the number and
    arrangement of carbon atoms in the molecules. As a general rule, at
    ambient temperatures, compounds with molecules containing up to 4
    carbon atoms are gaseous; those with 5-20 carbon atoms, liquid; and
    those with more than 20 carbon atoms, solid. In crude oil, gaseous and
    solid compounds occur dissolved in the liquid fraction. Solidification
    of crude oils is caused by the presence of waxy normal paraffins of
    high relative molecular mass. Unsaturated hydrocarbons such as olefins
    and alkynes do not occur in crude oils.

        Crude oils are similar to coal in that they are greatly enriched
    in carbon and hydrogen compared with the average composition of the
    earth's crust. Both are excellent sources of carbon for chemical

        The sulfur content of crude oil ranges from less than 2 to
    60 g/kg, depending on the origin of the oil. The sulfur is present not
    only as sulfide but also as mercaptans, thiophenes, and more complex
    organic sulfur compounds. The level of organic nitrogen compounds in
    most crude oils is less than 1 g/kg, but some may occasionally contain
    as much as 20 g/kg. Nitrogen compounds in crude oil are complex and
    mostly unidentified structures, which, through thermal decomposition
    during the distillation process of crude oil, are converted to simpler
    structures. Crude oils may also contain some naphthenic acids and
    phenolic compounds (Petroleum Handbook, 1966).

        As crude oils are the decomposition products of former aquatic
    animal and plant organisms, it is not surprising that they contain
    most, if not all, of the known elements. These are mainly present in
    few small quantities, i.e., only in mg/kg or small fractions of mg/kg.
    However, nickel, molybdenum, and mercury levels are sometimes as high
    as 10 mg/kg and vanadium levels, 50 mg/kg (Mason, 1966; Bertine &
    Goldberg, 1971). More complete coverage of crude oil trace elements
    can be found in BP (1975).

        Crude oils vary widely in appearance and consistency from country
    to country and from field to field. They range from yellowish brown,
    mobile liquids to black, viscous semi-solids. The differences are due
    to the different proportions of the various molecular types and sizes
    of hydrocarbons. One crude oil may contain mostly paraffins, another
    mostly naphthenes. Whether paraffinic or naphthenic, one may contain a
    large quantity of lower hydrocarbons and be mobile or contain a lot of
    dissolved gas; another may consist mainly of higher hydrocarbons and
    be highly viscous, with little or no dissolved gas. The nature of the
    crude oil governs, to a certain extent, the nature of the products
    that can be manufactured from it and their suitability for special
    applications. A naphthenic crude oil will be more suitable for the
    production of asphaltic bitumen, a paraffinic crude oil for wax. A
    naphthenic crude oil, and even more so an aromatic one, will yield
    lubricating oils with viscosities that are sensitive to temperature.
    However, with modern refining methods there is greater flexibility in
    the use of crude oils to produce any desired type of product. Crude
    oils are usually classified into three groups, according to the nature
    of the hydrocarbons they contain:

    (a) Paraffin base crude oils

        These contain paraffin wax, but little or no asphaltic matter.
    They consist mainly of paraffinic hydrocarbons and usually give good
    yields of paraffin wax and high-grade lubricating oils.

    (b) Asphaltic base crude oils

        These contain little or no paraffin wax, but asphaltic matter is
    usually present in large proportions. They consist mainly of
    naphthenes and yield lubricating oils that are more viscosity
    sensitive to temperature than those from paraffin base crude oils.
    These crude oils are now often referred to as naphthene base crude

    (c) Mixed base crude oils

        These contain substantial amounts of both paraffin wax and
    asphaltic matter. Both paraffins and naphthenes are present together
    with a certain proportion of aromatic hydrocarbons.

        This classification is a rough-and-ready division into types and
    should not be used too strictly. Most crude oils exhibit considerable
    overlapping of the types described and by far the majority are of the
    mixed base type (Petroleum Handbook, 1966).

        A useful compilation of the various characteristics and
    approximate composition of most relevant crude oils is given in Anon

    2.1.2  Methods of sampling and analysis

        As the methods of sampling and analysis are the same for crude
    oils, petroleum solvents, and lubricant base oils, a general
    discussion follows.

        The petroleum products dealt with in this document are mostly
    complex mixtures of closely related chemical compounds, identified as
    a product on the basis of certain physical and chemical
    characteristics related to their intended use. Because of the complex
    nature of these products, only some of the relatively simple,
    low-boiling components can be determined individually, and even these
    cannot be selectively monitored in the working area without
    appreciable expense. Thus monitoring for groups of compounds such as
    "total hydrocarbons", etc. is often unavoidable. The objective of the
    analysis will, in general, be to determine the concentration of any
    particular suspected component class rather than to identify the
    product. Moreover, because of differences in the volatility,
    solubility, etc. of the components, the product will lose its
    "identity" the moment is escapes from its original confinement and
    enters the environment.

        Potential health hazards associated with handling petroleum
    products mainly arise from skin contact and inhalation. By proper
    precautionary measures, the risk of skin contact can easily be
    controlled. The occurrence of air contaminants, however, quite often
    escapes human perception and this section will be devoted to ways of
    assessing levels of contaminants in air.

        Based on their different toxicological behaviour, 3 classes of
    air contaminants can be distinguished, namely: gases and vapours
    (from, e.g., solvents, petrol); mists (from, e.g., higher-boiling
    refined oils); and fumes (from, e.g., high-boiling aromatic extracts,

        Sampling and analysis for these 3 classes will be discussed
    separately and particular attention will be given to single components
    at present considered to be the most hazardous, such as benzene,
     n-hexane, and polycyclic hydrocarbons.

        Though, in the context of this Environmental Health Criteria
    document, methods for the monitoring of both the air in the workplace
    and the ambient air are relevant, only methods for work-place
    monitoring will be briefly reviewed. The most sensitive methods for
    monitoring work-place air could also be used for monitoring the
    generally much lower levels in the ambient air.

        The most frequent reason for sampling the air in the workplace is
    to measure the concentration of hazardous agents to which the worker
    may be exposed. The preferred way of assessing the exposure level is
    to determine the time-weighted average (TWA) concentration for a
    normal 8-h working day in the breathing zone of an individual worker.
    For area monitoring, fixed station or portable monitors are used. Data
    obtained in this way are independent of the presence and movement
    pattern of the worker.

        A detailed description of sampling strategy is given, for
    instance, in NIOSH (1977a).

        An alternative method for the determination of the amount
    absorbed by a worker is biological monitoring, i.e., assessment of the
    absorbed substance or its metabolites in biological material (urine,
    blood, expired air). Such methods are available for many substances,
    but unfortunately not for petroleum products, with the exception of
    benzene and its homologues and, to a certain extent,  n-hexane. The
    principles of biological monitoring have been reviewed by many
    authors, e.g., Piotrowski (1977).

        The types of pollutants that occur in the work-place can be
    divided into 2 broad categories, based on their physical state,
    namely: gaseous pollutants and aerosols. Methods for sampling gaseous
    pollutants are different from those for aerosols.  Gases and vapours

        For personal monitoring, sampling and analysis are usually
    performed in 2 separate steps. Samples are collected, mostly over a
    prolonged period of time, from the breathing zone of the worker by
    passing the contaminated air at a flow rate of 50-200 ml per min
    (using a personal sampling pump carried by the worker) through a small
    tube containing a suitable adsorbent (NIOSH, 1973; Clayton & Clayton,
    1978; Voborsky, 1980). For hydrocarbon vapours, activated charcoal is
    one of the best adsorbents.

        Recently, passive dosimeters, based on diffusion of the substance
    into an adsorbing layer, have been developed and marketed. Though
    laboratory studies have shown these dosimeters to be as accurate as
    adsorbent tubes using sampling pumps, more field data are needed to
    prove their validity.

        For grab samples, the contaminated air may also be collected in
    Tedlar, Mylar, or Saran bags or in gas pipettes. Such samples must be
    analysed as soon as possible, because of possible sample losses.

        The techniques used for personal monitoring can also be used for
    area monitoring. In many instances, however, the high specificity and
    accuracy that can be obtained by the sophisticated methods used for
    the analysis of personal monitoring samples is not required and
    relatively simple, direct reading instruments can often be used when
    searching for leakages, when monitoring areas with only a single
    substance as a contaminant, or when monitoring areas where the total
    hydrocarbon level is generally below the exposure limit for any of the
    individual substances of concern.

        The most simple direct reading instrument is the colorimetric
    indicator tube, usually used with a hand pump, a wide variety of which
    are available. However, while it is true that colorimetric indicator
    tubes are of low initial cost and simple and convenient to use, there
    are distinct limitations and potential errors inherent in this method.
    A manual describing the applications and limitations of these devices
    is available (AIHA, 1976). Other, commercially available, direct
    reading instruments include portable infrared instruments, portable
    gas chromatographs, and non-specific analysers, such as total
    hydrocarbon analysers (ACGIH, 1978b).

        An analytical procedure may, however, include several of the
    following steps: sample recovery, concentration, pre-separation,
    derivatization, and analysis.

        The sample can be recovered from solid collection media by
    solvent extraction or by thermal desorption. When a liquid absorbent
    is used, a concentration step may be required.

        Very many analytical techniques are available. However, as the
    quantities of organic material to be determined are generally minute
    and concealed in a matrix of many other substances, some analytical
    techniques are especially suitable, such as gas chromatography (GC),
    gas chromatography and mass spectrometry (GC/MS), and high-pressure
    liquid chromatography (HPLC) with ultraviolet or fluorescence

        Criteria for the choice of analytical technique include:
    specificity required; quantities involved; ease of operation;
    suitability for automation; and cost per analysis.

        The principles of the analytical techniques mentioned are
    described extensively in many monographs. For example a short
    description of all relevant analytical techniques is given in NIOSH
    (1973). Thus, only those for total hydrocarbons,  n-hexane, and
    benzene will be discussed here.

    (a) Total hydrocarbons

        Colorimetric indicator tubes are available from most
    manufacturers for the determination of total hydrocarbons in the
    work-place air. These tubes normally cover the range from about
    100 ppm to several thousand ppm (corresponding to gasoline levels
    ranging from 450 mg/m3 to several grams per m3 if a conversion
    factor of 4.5 is applied). Many commercial instruments are also
    available (ACGIH, 1978), the most reliable being those based on flame
    ionization detection. These methods are generic in nature and the
    instruments have to be calibrated, e.g., against methane or
     n-octane. The read-out is not absolute, as the detector response
    differs according to the composition of the hydrocarbons.

    (b)  n-Hexane

        Depending on the situation, one of the 2 following approaches can
    be applied in analysing specifically for  n-hexane:

        (i)  n-Hexane as the main contaminant: direct area monitoring
    can be performed using either a flame ionizing detector, without
    previous separation (total hydrocarbon detector), or the total
    hydrocarbon or low range  n-hexane colorimetric indicator tubes
    ( n-hexane tubes are non-specific and react to all hydrocarbons; the
    range is from about 20 mg/m3 upwards).

        The NIOSH method S-90 (NIOSH, 1977-79), using the charcoal
    tube/carbon disulfide desorption method with GC-analysis on packed
    columns is suitable for personal monitoring.

        (ii)  n-Hexane present as one of the constituents of a
    hydrocarbon mixture: In this case the matrix is very complicated. It
    is more or less a prerequisite to use capillary GC to obtain a
    satisfactory separation. Sample recovery is preferably carried out
    with a 2-step thermal desorption, though solvent desorption using a
    solvent with a longer retention time on the GC column (e.g., decane)
    could be used.

        Recently, it has been suggested that the urinary excretion of
    hexane metabolites could be used for monitoring occupational exposure
    to n-hexane and its isomers (Perbellini et al., 1981).

    (c) Benzene

        If benzene is the main pollutant, total hydrocarbon analysers,
    or, even better, the benzene colorimetric indicator tubes can be used
    (ranges available: from 0.15 to 150 mg/m3, sensitive to other
    aromatic compounds, somewhat sensitive to hydrocarbons).

        In all cases, the personal monitoring charcoal-tube/carbon-di-
    sulfide-desorption/GC-analysis method can be used, i.e., NIOSH method
    S-311 (NIOSH, 1977-79).

        A detailed description of the determination of benzene in work
    environments can be found in CONCAWE (1981a).

        Biological monitoring for benzene exposure is carried out by
    measuring the elimination of phenol (metabolite of benzene) in urine.
    Several colorimetric methods (using 2,6-dibromo- N-chloro-
     p-benzoquinoneimine-Gibbs reagent, 2,6-dibromoquinone-4-chlorimide,
    diazo- p-nitroaniline or 4-dimethylamino-2,3-dimethyl-l-phenyl-
    3-pyrazolin-5-one (4-aminopyrine)) or gas chromatographic methods are
    available. A concentration of phenol in urine of more than 25 mg/litre
    indicates some exposure to benzene (Truhaut & Murray, 1978).  Aerosols

        The sampling of aerosols is performed by drawing a measured
    volume of air through a filter, an impaction or impingement device, or
    an electrostatic or thermal precipitator. The most common method,
    especially for personal monitoring, consists of drawing air, at a
    well-defined rate, through a filter. For personal monitoring, a
    portable pump and a suitable filter in a filter-holder, located in the
    worker's breathing zone, is used.

        For area monitoring, some direct reading instruments for grab
    sampling are also available based on, e.g., light-scattering,
    attenuation of beta radiation, and changes in the resonant frequency
    of a piezoelectric quartz crystal (ACGIH, 1978).

        In some cases, size-selective sampling is necessary. This can be
    accomplished by placing a cyclone or elutriator in front of the
    sampler, or by the use of special-size selective sampling devices.
    When, however, the aerosol also presents a hazard through absorption
    via the gastrointestinal tract, total particulate matter should be

        In many instances, the total particulate concentration in air is
    the only information needed, in which case, a gravimetric
    determination of the material collected is all that is required.

        On the other hand, if it is necessary to determine the
    benzene-soluble matter present in the total particulate matter
    collected, the collected matter must first be extracted with benzene.
    The extract must then be evaporated to dryness and the residue weighed
    (NIOSH, 1977-79). When more detail is required concerning the
    composition of the aerosol collected, the benzene extract should be
    analysed for the substances of concern.


        Aerosols generated from refined oils and oils with a relatively
    low aromatic content are often referred to as mists. The methods of
    analysis most frequently used for mists consist of drawing air, at a
    well-defined rate, through a preweighed and preconditioned glass-fibre
    filter and recording the weight gain. If the weight gain indicates
    that the total particulate concentration in the work atmosphere is
    well below the appropriate exposure limits, no further analytical
    action is required for the air sample. However, when concentrations in
    excess of such levels are found, investigators invariably require
    determination of the oil content of the filter.

        For this purpose, the filter is extracted with a suitable solvent
    and the oil content of the extract determined, either gravimetrically
    (after evaporation of the solvent) or spectrophotometrically, using
    ultraviolet or infrared adsorption or fluorescence spectrophotometry
    (CONCAWE, 1981b; NIOSH, 1977-79).

        The exposure limits for mists are mainly established as total
    particulate oil mist and, for general investigations and control work,
    it is recommended that sampling should be designed to take this into
    account. Nevertheless, there may be some occasions when the
    investigator feels it necessary to assess the concentration of
    respirable particles in the mist, and special sampling techniques,
    e.g., using a cyclone, will need to be employed. Experience, however,
    does suggest that, in general, the equivalent diameter of particles '
    in oil mists in engineering workshops is well below 5 µm and hence
    they may be regarded as respirable. Thus, it is common industrial
    practice to sample for total particulate matter.

        For area monitoring, one of the direct reading devices mentioned
    earlier could also be used.


        Aerosols generated from high-boiling aromatic extract oils and
    bitumens are called fumes.

        Where exposure to fumes from materials containing significant
    concentrations of polycyclic aromatic hydrocarbons, such as aromatic
    extract oils, is likely to occur, some guidance can be gained from the
    AGGIH TLV-TWA of 0.2 mg/m3 for particulate polycyclic aromatic
    hydrocarbons (as benzene-soluble material BSM). Coal tar pitch
    volatiles include the fused polycyclic hydrocarbons that volatilize
    from the distillation residues of coal, petroleum, wood, and other
    organic matter. In the case of aromatic extract oils, the fact that a
    major part of the BSM consists of non-polycyclic aromatic compounds
    should be taken into account (NIOSH, 1977b).

        With regard to the present standard for BSM, the analytical
    method is as follows: total particulate matter suspended in air is
    collected on a glass-fibre filter, with a silver membrane back-up
    filter. The filter is extracted with benzene, using ultrasonic
    agitation. An aliquot of the extract is evaporated to dryness and the
    residue is weighed (NIOSH, 1977-79).

        If it is felt necessary to characterize more fully the polycyclic
    aromatic hydrocarbons (PAHs) present in the benzene extract of the
    fume samples. further analysis of these extracts can be performed as

    (a)  GC method (Grimmer & Böhnke, 1972; Grimmer, 1979): The filter
         extract is treated in several steps to isolate a fraction,
         enriched in PAHS. This fraction is then analysed by capillary
         GC/MS. For very complex products, the aerosol composition might
         be too complicated to obtain a reasonable chromatogram, even
         after all the pre-separation steps.

    (b)  HPLC separation with fluorescence detection (Das & Thomas, 1978;
         Belinky, 1980).

         The filter extract is evaporated and dissolved in 0.5-1 ml of
         benzene. This extract is directly injected into the HPLC
         instrument. As the fluorescence detector only records the highly
         unsaturated molecules, the larger part of the matrix does not
         give any signal at all on the detector. Only the
         alkyl-substituted and unsubstituted polycyclic aromatic compounds
         give rise to a detector signal.

         Specificity for selected substances can be increased
         substantially by a proper choice of excitation and emission
         wavelengths. For the more volatile polycyclic aromatic
         hydrocarbons, like pyrene, some losses may occur during sampling,
         due to volatilization. If these more volatile polycyclic aromatic
         hydrocarbons are also of interest, the filter collector could be
         backed up by a silicagel tube. The silicagel from this tube is
         then treated in the same way as the filter.

    2.2  Sources of Environmental Pollution

    2.2.1  Natural occurrence

        Crude oils are exclusively natural products, most of which are
    produced from artificial wells. Natural seepage of crude oils occurs
    in various parts of the world, not only on land, but also on the
    sea-bed; however, this represents only a minor source of environmental
    pollution in comparison with man-made sources.

    2.2.2  Man-made sources  Production

        Taking world-wide figures, total crude oil production for 1973
    was about 2900 million tonnes, i.e., approximately 10 times the crude
    oil production in 1938. The rate of growth of production has declined
    since 1973 (the 1979 level was just over 3200 million tonnes), and
    very little overall increase, if any, is expected in the near future.  Uses

        In some areas, e.g., Japan, certain unrefined crude oils are used
    as fuels.

        Negligible amounts of unrefined oils are used for such
    applications as road construction and malaria control.

        In some areas, where crude oils come to the surface in natural
    seepage, they have been used by the local population, since
    prehistoric times, for a number of purposes, but mainly for heating
    and lighting.

        Nearly. all the crude oil produced is processed in refineries
    into various fuel and non-fuel fractions.

        An example of an integrated flow scheme for the processing of
    crude oil is shown in Fig. 1. The crude oil distillation (a
    straightforward distillation process) and subsequent
    vacuum-distillation (distillation under high vacuum) of the residues
    of the first process splits crude oil into its basic fractions which,
    after further treatment, purification, and sometimes blending with
    additives, are used as commercial products. The major petroleum
    fractions are listed in Table 1 in broad categories according to
    increasing boiling-point.

        Certain petroleum fractions, such as naphtha or wax can be
    submitted to various thermal or catalytic cracking processes and to
    other refinery processes such as alkylation, and isomerization. In the
    course of these processes, long-chain paraffinic hydrocarbon molecules
    are broken down into smaller molecules including unsaturated
    (olefinic) compounds. Some of these olefins may stay in the
    end-product of the cracking process, others, especially if under the
    influence of high temperatures and catalysts, will react among each
    other and form more complex structures ranging from iso-octanes to
    polynuclear aromatic hydrocarbons (Badger, 1962).

        The products obtained from cracking processes can be distilled
    into various fractions in a similar way to crude oils, though
    obviously the composition of the fractions is different. For instance,
    they contain a certain percentage of olefins that are highly valued as
    base materials for the chemical industry. By suitable choice of
    cracking procedures, the yield of special compounds such as gasoline
    components or olefins can be boosted. On the other hand, fractions
    derived from the cracking of petroleum products contain a higher
    percentage of polynuclear aromatic hydrocarbons than corresponding
    straight-run crude oil fractions. The implications of this will be
    discussed later.

    TABLE 1.  Range of major petroleum fractions

    Fuels                    Boiling range     Non fuels

    natural gas
    refinery gas
    liquefied petroleum      <10 °C
    gas (LPG)

    gasolines                 35 °C            petroleum solvents
    kerosenes                                  naphtha
    gas oils                 300 °C

    heavy fuel oils          300 °C            base oils also used for
                                               lubricating, metal
                                               working and textile oils
                             700 °C            petroleum waxes

                             >700 °C           bitumens, coke


        Examples of olefinic base chemicals derived from cracking
    processes are: ethylene, acetylene, propylene, butylenes, pentenes,
    and higher aliphatic olefins, such as butadiene, isoprene.

        It is outside the scope of this review to give further details
    and other refining processes.

    FIGURE 1  Disposal of waste

        In a refining process, the release of oil into refinery effluents
    is practically negligible and of a lower order of magnitude than
    tanker washings in tankers that do not use the "load-on-top" system.
    Waste gas in production fields is generally burnt on the spot. In
    refineries and chemical plants, it may be necessary to burn some gas
    at a flare for reasons of safety, and some oil and gas is consumed as
    refinery fuel. Atmospheric pollutants in and around refineries
    basically consist of saturated and unsaturated hydrocarbons, carbon
    monoxide, hydrogen sulfide, and sulfur dioxide (Poliansky &
    Musserskaja, 1971; Krasovitskaja, 1976). Sulfur dioxide, hydrogen
    sulfide, and mercaptan emissions are not discussed in this review and
    emissions of hydrocarbon vapours into the atmosphere from storage
    terminals, filling stations, and cars will be covered in another

    2.3  Toxicological Effects of Crude Oils

        As, in this document, crude oils are discussed only to provide
    background information for the petroleum solvents, lubricating base
    oils, and bitumens derived from them, no detailed discussion will
    follow concerning environmental exposure levels, environmental
    distribution and transport, physiological factors relating to
    mammalian uptake, dose-response relationships, and maximum permissible
    levels. Most of the relevant aspects will, however, be covered in the
    sections on fractions derived from the crude oils. This also applies
    to toxicological effects on experimental animals and man, with the
    exception of a very few studies that are related to crude oil exposure

        The toxicological and nuisance aspects of hydrogen sulfide and
    mercaptans have been reviewed in detail by Miner (1969) and Sullivan
    (1969). A review on hydrogen sulfide has been prepared by NIOSH
    (1977c) and an Environmental Health Criteria document on hydrogen
    sulfide has recently been published (WHO, 1982).

    2.3.1  Effects on experimental animals

        Leitch (1924) examined 16 untreated crude oils from various parts
    of the world for their carcinogenicity by applying them 3 times a week
    to the skin of mice and found significant differences in
    tumorigenicity among these oils. Similar results were reported by
    Hieger & Woodhouse (1952) in skin tests on mice and rabbits. The
    tumorigenicity of the crude oils they examined was low in comparison
    with that of some of the distilled fractions. Skin tests were also

    carried out on mice and rabbits by Antonov & Lints (1960), who found
    that Saratov oil possessed weak carcinogenic properties. The main
    causes of death in these tests, however, were pneumonia and general
    intoxication, probably from absorption of oil components through the
    skin. The authors found that rabbits were more sensitive than mice, as
    did Hieger & Woodhouse (1952).

        Batt-Neal & Wolman (1977) demonstrated skin tumorigenicity and
    amyloid deposition following skin exposure of mice to saturated
    acetone extracts of various oils collected from beaches.

    2.3.2  Effects on man

        Examination of 743 oilfield workers exposed to California crude
    oil and excessive sunlight revealed that 7 of them had epitheliomas on
    exposed parts of the body and that nearly 20% had keratotic changes on
    the hands, forearms, face, and neck. Five of the 7 subjects, who
    developed epitheliomas, were blonds, though blonds were in the
    minority in this group of workers (Schwartz et al., 1947).

        During 1938-39, Schwartz saw 189 cases of carcinomas on exposed
    parts of the skin; 128 were in males, 71 of whom were oilfield workers
    20 others being workers exposed to excessive sunlight only. Emmett
    (1975) mentions the strong potentiating effect of UV radiation on
    other potentially carcinogenic exposures. In southern Texas, however,
    the incidence of skin carcinomas in 330 oilfield workers was low,
    which underlines the fact that Texas and Pennsylvania oils are known
    to be less carcinogenic than California oil (Twort & Ing, 1928).

        In a study on 50 volunteer operators, who had not previously been
    in contact with oil and petroleum products, crude oil was applied to
    the skin of the inner surface of the forearm, for periods of 3-6 h. An
    inflammatory reaction of the skin developed with moderate erythema,
    oedema, and slight burning. Changes in the thermosensitive threshold
    were noted, as well as an increase in the permeability of the
    epidermis (Gusein-Zade, 1975).


    3.1  Properties and Analytical Methods

    3.1.1  Chemical composition and properties

        Only solvents consisting of hydrogen and carbon alone and
    produced from petroleum will be considered in this review. It should
    be noted, however, that similar solvents are also produced from coal.

        Petroleum solvents consist of complex mixtures of hydrocarbons
    reflecting the hydrocarbon constituents of the crude oil or, more
    usually, the intermediate refinery streams from which they are
    distilled. Because of their complex nature, classification is a
    problem and no standard, worldwide-accepted nomenclature exists.
    However, providing that it is recognized that considerable overlapping
    and many exceptions occur, they can be classified into 3 broad
    subdivisions, based on distillation ranges:

    (a)  special-boiling-point solvents (SBPs) - grades with narrow or
         wide distillation ranges within the main limits of 30-160°C;

    (b)  white spirits - grades distilling within the main range
         150-220°C, the boiling-points of individual grades usually
         ranging over more than 20°C;

    (c)  high-boiling aromatic solvents - grades distilling in the range
         160-300°C with final boiling-points above 220°C.

        Benzene, toluene, and the xylene isomers occur as components of
    petroleum solvents, but as they fall more naturally into the category
    of chemical intermediates, they will be referred to here only in so
    far as they are important as components of the mixtures being

        Two further clarifications can be made. Firstly, it is common
    industrial practice to ascribe the name of the predominant isomer
    present to the petroleum solvent; thus the descriptions pentane,
    isopentane, hexane, isohexane, and heptane are commonly met. However,
    in almost all cases, the amount of the named isomer present in an
    industrial scale product will not exceed 95% v/v of the solvent and
    may be as small as 30% v/v.

        Second, most petroleum solvents are marketed on the basis of
    typical physical properties rather than on chemical specifications,
    because of the limitations during refining of controlling the complex
    mixtures of isomers that make up the petroleum solvents. As production
    techniques become more sophisticated, greater control is possible and
    more properties can be specified within narrower limits. However, even
    when such narrow limits are met, the mixture of components present may
    vary, because of variations in the types of crude oil being processed
    and alterations in conditions in processing units.

        To meet the wide range of properties required by the market,
    several different processes are used. Distillation is the common
    process setting the volatility range. Chemical conversion techniques,
    including reforming, alkylation, and hydrogenation, alter the chemical
    composition and hence the solvency, as do physical conversion
    techniques such as solvent extraction and molecular sieve separation.
    Specific treatments such as caustic soda and sulfuric acid washing and
    clay percolation are frequently applied to remove odourous substances,
    chiefly sulfur compounds.

        The reader is referred to Boenheim & Pearson (1973) for detailed
    discussions of the chemical and physical composition and uses of
    petroleum solvents.  Special-boiling-point solvents (SBPs)

        These are highly purified naphtha fractions with specially
    selected boiling ranges. The boiling range may be narrow or wide, and
    generally falls within the limits of 30-160°C: SBPs are classified
    according to their boiling range, e.g., SBP 62/82. Petroleum ether,
    lighter fluid, spot remover, and rubber solvent are consumer products
    in this range. Generally, SBPs consist of a mixture of hydrocarbons in
    the C-5 to C-9 range: normal and branched paraffins, cycloparaffins,
    and aromatic compounds. They contain only traces of olefins. An
    example of the composition of a typical sample of straight run (i.e.,
    non-dearomatized) SBP 80/110 is given in Table 2.  White spirits

        The boiling-range of this group of solvents falls within the
    limits 150-220°C (intermediate between gasoline and kerosene). These
    solvents can be classified into low-aromatic grades (approximately
    15-20% aromatic hydrocarbons) and high-aromatic grades (45% or more
    aromatic hydrocarbons). They generally consist of hydrocarbons in the
    C-7 to C-12 range, again including normal and branched paraffins as
    well as naphthenic (cycloparaffins) and aromatic compounds. Olefins
    are present in trace amounts only. Stoddard solvent, mineral spirits,
    low-aromatic white spirits (LAWS) and turpentine-substitute are
    well-known examples from this range.  High-boiling aromatic solvents

        Aromatic hydrocarbons occur naturally in certain crude oils in
    widely varying concentrations. They are also formed during secondary
    processes such as thermal and catalytic reforming. They can be
    concentrated and extracted by solvent extraction.

        Apart from benzene, toluene, and xylene, which will not be
    discussed separately in this review, this group includes solvents with
    an aromatic content of 80-100%, and a wide boiling-range from 160 to
    300°C. High-boiling aromatic solvents are obtained by distillation or
    solvent extraction from refinery fractions such as kerosene and
    lubricating base oils, and consist of very complex mixtures of
    hydrocarbons with more than 9 carbon atoms per molecule. The
    composition of a typical sample of one of these aromatic hydrocarbons
    from the middle range (distillation range approximately 192-203°C) is
    given in Table 3.

        Most aromatic solvents are highly purified "white" solvents.
    Those in the higher boiling range, derived from lubricating base oil
    stocks by solvent extraction, may be less pure and coloured. They are
    often by-products and are used as solvents for various technical
    purposes. In many cases, they are referred to as "processing oils"
    instead of solvents, and considered under lubricating oils.

    3.1.2  Purity of petroleum solvents

        In these complex mixtures, impurity is, of course, a matter of
    definition. Components that are taken out in the course of the various
    refining and treating processes used to obtain the more pure solvents
    could be regarded as such. The major impurities would then be sulfur
    compounds such as hydrogen sulfide, mercaptans, and thiophens, as well
    as, olefins and other reactive unsaturated hydrocarbons.

        A second category of impurities includes the hydrocarbons that
    have been demonstrated to be carcinogenic in animals and man, such as
    benzene, the polynuclear hydrocarbons and related heterocyclic
    compounds containing nitrogen or sulfur.

        TABLE 2. Composition of typical sample of SBP 80/110a

    Hydrocarbon   Hydrocarbon                    % mass present        Boiling
    type                                           in sampleb         point °C

    normal        n-pentane                            0.2              36.2
    paraffins     n-hexane                             8.2              69.0
                  n-heptane                           17.2              98.4

    branched      2 methyl butane Tc                   0.1              27.9
    paraffins     2,2 dimethyl butane T               trace             49.7
                  2,3 dimethyl butane T                0.3              58.0
                  2 methyl pentane                     1.5              60.3
                  3 methyl pentane                     1.6              63.3
                  2,2 dimethyl pentane                 1.0              79.2
                  2,4 dimethyl pentane                 1.3              80.5
                  2,2,3 trimethyl butane T             0.3              80.9
                  2,3 dimethyl pentane                 9.7              89.8
                  3 methyl hexane                      9.2              91.9
                  3 ethyl pentane                      3.1              93.5
                  2,2,4 trimethyl pentane             trace             99.2
                  2,2 dimethyl hexane                 trace            106.8
                  2,5 dimethyl hexane                  0.6             109.1
                  3,3 dimethyl hexane T               trace            112.0
                  2,3 dimethyl hexane                  0.8             115.66
                  3,4 dimethyl hexane                 trace            117.7
                  3 methyl heptane                     0.5             118.9

    cyclo C-6     cyclohexane                          8.4              80.7
    paraffins     methyl cyclohexane                  14.2             100.9

    cyclo C-5     cyclopentane T                      trace             49.3
    paraffins     methyl cyclopentane                  4.7              71.8
                  1,1 dimethyl cyclopentane T          2.9              87.9
                  1-cis-3-dimethyl                     1.9              90.8
                  cyclopentane T

    TABLE 2. (contd).

    Hydrocarbon   Hydrocarbon                         % mass present    Boiling
    type                                                in sampleb     point °C

    cyclo C-5     1-trans-3-dimethyl                        2.7          91.7
    paraffins     cyclopentane T
    contd.        1-trans-2-dimethyl                        0.5          91.9
                  cyclopentane T
                  1-cis-2-dimethyl cyclopentane T           0.5          99.5
                  ethyl cyclopentane                        0.6         103.5
                  1,1,3 trimethyl cyclopentane T            0.8         104.9
                  1-trans-2-cis-4-trimethyl                 0.4         109.3
                  cyclopentane T
                  1-trans-2-cis-3-trimethyl                 0.4         110.2
                  cyclopentane T
                  1,1,2 trimethyl cyclopentane T            0.3         113.7

    unidentified                                                        Probably
    paraffins                                               1.1         110.0

    aromatic      benzene                                   0.7          80.1
    compounds     toluene                                   3.9         110.6

    olefins                                                 0.4

    a  From: Shell International Petroleum Co., London (unpublished data).
    b  Average of duplicate analyses.
    c  T = tentative identification.

    TABLE 3. Composition of typical sample of Solvesso 150a

    Hydrocarbon                              % v/v of solvent

    n-butylbenzene                                  2.47
    sec-butylbenzene                                0.08
    tert-butylbenzene                               0.05
    m-cymene                                        0.13
    o-cymene                                        0.01
    p-cymene                                        0.52
    1.2-diethylbenzene                              1.72
    1.3-diethylbenzene                              1.10
    1.4-diethylbenzene                              0.56
    1.2-dimethyl-3-ethylbenzene                     2.86
    1.2-dimethyl-4-ethylbenzene                     6.64
    1.3-dimethyl-2-ethylbenzene                     0.71
    1.3-dimethyl-4-ethylbenzene                     4.17
    1.3-dimethyl-5-ethylbenzene                     2.80
    1.4-dimethyl-2-ethylbenzene                     3.26
    m-ethyltoluene                                  0.37
    o-ethyltoluene                                  0.02
    p-ethyltoluene                                  0.01
    indane                                          0.46
    isobutylbenzene                                 0.32
    isopropylbenzene                                0.01
    1-methyl-3-t-butylbenzene                       0.76
    1-methyl-2-n-propylbenzene                      1.26
    1-methyl-3-n-propylbenzene                      2.08
    1-methyl-4-n-propylbenzene                      1.93
    1-methylindane                                  0.91
    2-methylindane                                  2.43
    4-methylindane                                  9.28
    5-methylindane                                  2.02
    naphthalene                                     4.03
    n-propylbenzene                                 0.00
    1.2,3,4-tetramethylbenzene                      3.66
    1.2,3,5-tetramethylbenzene                      8.84
    1.2,4,5-tetramethylbenzene                      5.53
    toluene                                         0.02
    1.2,3-trimethylbenzene                          0.10
    1.2,4-trimethylbenzene                          0.05
    1,3,5-trimethylbenzene                          0.01

    a Courtesy Esso Standard Oil Company, New York, N.Y.,
      USA (From: Gerarde, 1960).

    TABLE 3. (contd).

    Hydrocarbon                              % v/v of solvent

    m-xylene                                        0.05
    o-xylene                                        0.03
    p-xylene                                        0.03
    C-11-naphthalenes                               0.31
    C-11-indanes                                    3.58
    C-11-alkylbenzene                              18.27
    C-12-alkylbenzene                               0.73
    C-12-indanes                                    0.08
    C-13-alkylbenzene                               0.02
    C-10-indenes                                    0.10
    C-11-indenes                                    0.07
    C-12-naphthalenes                              trace
    C-12-indenes                                    0.10
    aromatic compounds                 Total       94.55

        Generally, the total sulfur content, the olefin content, and the
    total aromatic content are specified for commercial petroleum
    solvents. Where special products such as food-grade materials are
    concerned, the benzene content is specified as well as the UV
    absorption limits at certain wavelengths, as a measure of the
    polynuclear aromatic hydrocarbon content.

    3.1.3  Methods of sampling and analysis

        See section 2.1.2.

    3.2  Sources of Environmental Pollution

    3.2.1  Natural occurrence

        Petroleum solvents do not occur in nature as such, but only as
    components of the crude oils from which they are derived.
    Environmental pollution is always man-made and related to the use of
    the solvents.

    3.2.2  Man-made sources  Production

        Because there is no uniform system of definition and
    classification of petroleum solvents, firm statistics concerning the
    magnitude of production of this group of materials do not exist. The
    best estimate of the world-wide production of the group of solvents
    would be 9 million tonnes for the year 1979.  Uses

        It is not feasible to give more than a general outline of the
    uses of the range of petroleum solvents.

    (a) SpeciaL-boiling-point solvents (SBPs)

        SBPs are mainly used as: solvents and thinners in lacquers and
    paints; extraction solvents for perfumes, for vegetable oils and oil
    and fats of animal origin; quick-drying solvents in printing-ink,
    coatings, and adhesives; lighter fuel; and for dry-cleaning and
    degreasing purposes.

    (b) White spirits

        White spirits are mainly used as: solvents and thinners for
    lacquers, paints, resins, and printing-ink; solvents in formulations
    of chemical products, e.g., pesticides; and for metal degreasing, wool
    degreasing, and dry-cleaning.

    (c) Aromatic extracts

        The higher-boiling and less-purified aromatic extracts have very
    good solvent properties for many polymers and are used as
    ex-tender-oils in rubber, plastics, and bitumens, and also as solvents
    in printing-ink and pesticide formulations. Furthermore, they can be
    used as base-materials in the manufacture of carbon black.

    3.3  Environmental Exposure Levels

        Specific data are not available concerning levels of petroleum
    solvents in air, water, food, or other environmental media. However,
    low concentrations of hydrocarbons found in mussels have probably been
    derived from petroleum hydrocarbons present in the environment
    (Ehrhardt & Heineman, 1975).

        Because of the relatively low boiling-range of these solvents,
    industrial exposure to vapour may sometimes be high. This is known to
    occur, especially in small workshops with insufficient ventilation,
    where, for example, adhesives are used routinely. Although a lot of
    consumer products may contain these solvents, excessive domestic
    exposure would not normally be expected unless neat solvent were used
    for cleaning purposes, indoors. Very limited, indirect exposure of the
    general population is possible following the use of these solvents as
    extractants in the production of food-grade vegetable oils.

        Exposure to the higher-boiling and less-purified aromatic
    extracts is mainly confined to occupational situations, where
    excessive skin-contact may occur, or exposure to vapour in processes
    carried out at elevated temperatures or with high-speed machines that
    could give rise to fumes or mists. This will be considered in detail
    under lubricating base oils.

    3.4  Environmental Distribution and Transformation

        Data on the distribution between media, environmental
    transformation and degradation, interaction with physical, chemical,
    or biological factors and bioconcentration, are not available for
    petroleum solvents.

        However some information exists concerning the behaviour and
    degradation of crude oil in water (Floodgate, 1972, Hellmann & Zehle,
    1972), and of hydrocarbons in general (Walker et al., 1975), and there
    is much information on the microbial degradation of individual
    petroleum hydrocarbons (Van der Linden & Thysse, 1965; Haines &
    Alexander, 1974).

        From these publications it can be seen that the subject is highly
    complex and many factors have to be taken into account, such as the
    composition of the oil product, the extent of dispersion into the
    medium, and climatic conditions.

    3.5  Metabolism

    3.5.1  Absorption

        The kinetics are determined by diffusion rates, solubility in
    fat, and the concentration gradients in the individual compartments of
    the body.

        The highly volatile C-5, C-6, and C-7 paraffins, cycloparaffins,
    and aromatic hydrocarbons readily pass across the alveolar membrane
    into the bloodstream and are transported within minutes to the central
    nervous system. Longer-chain homologues can, to a certain extent, also
    pass the alveolar membrane, but their principal effect is local. This
    was shown by Gerarde (1963) in studies on rats.

        The alveolar air and blood concentrations of white spirit have
    been measured in man following inhalation (Åstrand et al., 1975).
    Aromatic hydrocarbons were absorbed to a greater extent into the
    bloodstream than aliphatic hydrocarbons (approximate values being 62%
    and 50%, respectively). Similar uptake values in man were shown for
    the aromatic hydrocarbons, benzene and toluene, by Nomiyama & Nomiyama
    (1974), for xylene by Sedivec & Flek (1976), Åstrand et al. (1978),
    and Riihimäki et al. (1979), and for ethylbenzene by Bardodej &
    Bardodejová (1970). Nomiyama & Nomiyama (1974) demonstrated a much
    lower pulmonary absorption for  n-hexane, the only aliphatic compound
    that they tested; it was also rapidly excreted.

        The skin is only permeable to hydrocarbons of a certain size.
    With paraffinic substances, the maximum chain length appeared to be up
    to 14 C-atoms (Scheuplein & Blank, 1971). Aromatic compounds have a
    more compact structure and, in studies on guineapigs, Hoekstra &
    Phillips (1967) showed that compounds from this group with a higher
    number of C atoms could still pass the skin barrier.

        The absorption of vapours through the skin is of minor
    importance. For example, in man, whole body skin exposure to
    2250 mg/m3 (600 ppm) of toluene was equivalent to an inhalation
    exposure of less than 37.5 mg/m3 (10 ppm) (Riihimäki & Pfäffli,
    1978). However, absorption during immersion in liquid solvents may be
    considerable. Percutaneous absorption during immersion of both hands
    in pure xylene was equal to an inhalation exposure of 435 mg/m3
    (100 ppm) (Engström et al., 1977). The permeation of xylene is thus
    about 20 nmol/min per cm2 (Engström et al., 1977; Riihimäki, 1979)
    and that for toluene, 3 µmol/min per cm2 (Cohr & Stockholm, 1979).
    Cutaneous exposure was probably a major route of absorption in 2 cases
    of acute renal failure with oliguria, caused by exposure to diesel oil
    (Barrientos et al., 1977; Crisp et al., 1979).

        Data for absorption in the intestinal tract are not available,
    but it is presumed that it would resemble absorption in the alveoli
    rather than that through the skin.

    3.5.2  Distribution in the body

        Tissue hexane levels in rats, following inhalation of anaesthetic
    concentrations, were measured by Böhlen et al. (1973). The tissue
    distribution generally depended on exposure time and was proportional
    to the lipid content of an organ until saturation occurred. The liver
    was a special case for, as its lipid level changed rapidly, the
    saturation level varied. Hexane was also apparently bound to some
    blood components.

        Women working at conveyor belts gluing parts of rubber footwear
    had concentrations of petroleum solvents (no details on
    physicochemical properties given) in the blood ranging from 2 . 35 ±
    0.4 up to 4.6 ± 0.6 mg/litre at concentrations in the air of
    100-300 mg/ m3. The solvent concentration in the blood increased with
    increasing length of the working period from 1.6 mg/litre in the first
    year to 2.5 mg/litre after 3.5 years and 3.4 mg/litre after 7-8 years
    of service.

        Wistar rats were exposed to the solvents used in the factory at
    concentrations in air of 300-1000 mg/m3 for 30-45 days, 4 h/day. The
    concentration of solvent in the blood amounted to 0.45 ± 0.05 -
    1.2 ± 0.01 mg/litre (Lipovskij et al., 1977a).

        Transfer of petroleum solvents through the placenta was studied
    in 85 pregnant women workers in the rubber industry, who came into
    contact with petroleum solvents during work (physicochemical
    properties of the solvents not defined, concentration in the air of
    the operating premises 300 ± 10 mg/m3). The average level of solvents
    in the blood of 46 pregnant women, on whom abortion was performed, was
    1.27 ± 0.3 mg/litre. A level of 3.29 ± 0.6 mg/kg was found in the
    tissue of the embryo. Women giving birth to a child (39 women) had a
    level of solvents in the blood of 2.5 ± 0.3 g/litre, while the content
    in the blood of the umbilical cord was 3.5 ± 0.3 g/litre. The
    concentration of solvents in the blood of the newborn infants was
    twice that of the mothers.

        Pregnant Wistar rats were exposed to the same solvent at a
    concentration of 300 ± 10 mg/m3, for 48 days, 4 h per day. The
    solvent was present in the blood, brain, liver, placenta, uterus, and
    fetal tissues (Lipovskij et al., 1979).

    3.5.3  Biotransformation

        In both man and animals, the aliphatic hydrocarbons are generally
    considered to be biochemically inert and excreted in the same form
    (Williams, 1959). However, it has been shown that some normal alkanes
    will, at least in part, be oxidized by the mammalian organism. For
    example, Ichihara et al. (1969) demonstrated the oxidation of decane
    in animals such as mice and rats, and the oxidative pathway of
     n-hexane to hexane-2,5-dione and hexane-2,5-diol via
    methyl- n-butylketone has been well established (see for example
    Spencer et al., 1978).

        As far as the metabolism of the cycloparaffins and aromatic
    hydrocarbons is concerned, the half-life, form, and rate of excretion
    of each component of the solvent has to be considered. It should be
    mentioned, however, that the metabolism of individual compounds will
    not be discussed in this document and readers are referred to the
    reviews by Williams (1959) and Gerarde (1960).

        The carcinogenicity of the solvents is thought to be due to the
    presence of benzene and some of the polynuclear aromatic compounds.

    3.5.4  Elimination

        The elimination of the lower-boiling solvents (SBP type) in both
    animals and man is usually rapid and mainly occurs via the respiratory
    tract. However, in the case of ingestion of the heavier solvents
    (white spirits), elimination mainly takes place with the faeces
    (Browning, 1965).

    3.6  Effects on Experimental Animals

        It has been mentioned in section 3.1.1, that the petroleum
    solvents under discussion in this document are more or less complex
    mixtures of a range of hydrocarbons. For the commercial products, the
    specification given generally includes the specific gravity,
    boiling-range, and total content of aromatic hydrocarbons. The
    concentrations of individual components vary, within certain limits,
    with the source of the crude oil from which the solvent is derived,
    and with the processes by which it is produced. These facts should be
    kept in mind because:

    (a)  the toxicity data developed for a certain solvent-specification
         indicate the order of magnitude of the toxicity of this type of

    (b)  in practice it would be impossible and impracticable to carry out
         complete toxicity testing on every single solvent on the market.
         It is only sensible to develop toxicity data for typical
         representative samples of a certain boiling range and within a
         certain specification of aromatic content. In the evaluation of
         the results, however, the analytical composition of the material
         - especially its contents of  n-hexane, benzene, and polynuclear
         aromatic hydrocarbons should be taken into account.

    3.6.1  Short-term exposure

        Hine & Zuidema (1970) examined various aspects of the acute
    toxicity of 10 samples of petroleum solvents that contained components
    representative of the range of hydrocarbons found in commercial
    petroleum solvents. Four were aromatic solvents containing at least
    98% aromatic hydrocarbons (coded A) and 6 were non-aromatic solvents
    containing less than 1% aromatic hydrocarbons (coded S). The boiling
    ranges and principal components of the samples examined are given in
    Table 4.

        Acute oral, inhalation, and percutaneous toxicity and skin and
    eye irritancy were examined for all samples. Intratracheal aspiration
    was simulated with 2 samples and repeated skin irritation tests were
    carried out using 5 of the samples. Undiluted samples were used for
    the investigations, all of which were carried out on rats with the
    exception of skin and eye irritancy and skin toxicity rests in which
    rabbits were used.

        TABLE 4.  The boiling-range and principal components of solvents examined for
              acute toxicitya

    Sample  Boiling-range              Principal components

    A-1     281-286°F   (138-141°C)    C-8 aromatic compounds (ortho, meta, and
                                       paraxylene; ethyl benzene)
    A-2     362-398°F   (163-203°C)    C-9, C-10 and C-11 aromatic compounds
    A-3     364-408°F   (188-209°C)    C-10 and C-11 aromatic compounds
    A-4     384-507°F   (196-264°C)    C-11 to C-14 aromatic compounds
    S-1     149-166°F   (65-75°C)      C-6 normal and isoparaffins (hexanes) and
                                       naphthenes (cyclohexane, methylcyclopentane)
    S-2     196-220°F   (91-104°C)     C-7 normal and isoparaffins (heptanes) and naphthenes
                                       (methylcyclohexane, dimethylcyclopentane)
    S-3     313-356°F   (156-180°C)    C-9 and C-10 normal and isoparaffins and naphthenes
    S-4     368-395°F   (187-212°C)    C-11 and C-12 normal and isoparaffins and naphthenes
    S-5     345-402°F   (174-216°C)    C-12 isoparaffins
    S-6     384-500°F   (195-260°C)    C-13 to C-16 normal and isoparaffins and naphthenes

    a From: Hine & Zuidema (1970).
        The findings of Hine & Zuidema (1970) which are summarized in
    Table 5, showed that all the solvents tested could be considered of
    low hazard to health unless aspirated or inhaled in extremely high
    concentrations. Aromatic solvents were more toxic than non-aromatic
    materials, the dose of solvent required to kill 50% of rats, when
    administered orally or percutaneously, being lower for aromatic than
    for non-aromatic solvents. Skin and eye irritancy were also greater
    with aromatic solvents. The toxicity of the vapours could not be
    compared, because the volatility of samples varied greatly. All
    solvents induced similar toxic effects, whatever the route of

    administration, including central nervous system depression
    (characterized by incoordination, prostration, and coma) followed by
    death. Convulsions sometimes occurred. All solvents caused skin and
    eye irritation though, in general, as the chain length of the
    non-aromatic solvents increased their irritant properties decreased.
    Repeated skin exposure led to skin irritation and necrosis with all

        Hoekstra & Phillips (1963) found that light mineral oils, when
    applied topically to the skin of guineapigs, caused epidermal
    hypertrophy, hyperplasia, hyperkeratosis, and depilation. Examination
    of the effects of various oil fractions demonstrated that the main
    effect of the short-chain volatile paraffins was to defat the skin,
    while longer-chain and aromatic hydrocarbons had a dermatoxic effect
    that was related to the permeability of the skin to these compounds.
    The maximum dermatoxic effect was seen with hydrocarbons containing
    14-19 carbon atoms, while a transition to non-dermatoxicity occurred
    around 21-23 carbon atoms. This was confirmed with pure  n-paraffins,
    but variations may exist with other types of hydrocarbons.
    Simultaneous application of innocuous long-chain substances together
    with irritant short-chain substances greatly reduced their toxicity,
    though this effect was less marked with aromatic solvents.

        In further studies on the effects of inhaling the vapours of
    hydrocarbon solvents (Carpenter et al. 1977a, b, c), the acute (4-h
    exposure) LC50 and no-observed-adverse-effect concentrations were
    studied in rats cats, and dogs. Results are summarized in Table 6.

        These studies confirmed the occurrence of central nervous system
    depression and there was also evidence of respiratory tract irritancy.
    There were no marked or consistent differences between the species
    examined. The major factor determining the acute inhalation hazard was
    the volatility of the solvent, those containing 9 or more carbon atoms
    tending to be insufficiently volatile to produce concentrations high
    enough to be lethal over a short period of exposure. One exception was
    a "high naphthenic" solvent, which was peculiar also in that
    depression was not preceded by signs of irritation of the respiratory
    tract, so that there was no warning of overexposure. Increased
    aromatic content did not consistently result in increased inhalation
    toxicity, though earlier work (Lazarew, 1929) suggested that the acute
    inhalation toxicity of gasoline vapours increased with increasing
    contents of cycloparaffins and aromatic hydrocarbons. The narcotic
    action was also found to increase in each step by a factor of 3 in the
    series - pentane, hexane, heptane, and octane (Fühner, 1921). Swann et
    al (1974) found that anaesthesia occurred with these compounds at
    concentrations of 32 000 ppm or more and that respiratory tract
    irritation increased with chain length. Full anaesthesia can be
    produced with gasoline (Haggard, 1921), but anaesthetic concentrations
    are little lower than those that cause convulsions and death
    (Browning, 1965).

        TABLE 5. Toxicity of solvents. Summary of resultsa

    Test                 Sample         Result                   Classification

    Oral                  A-1        10.0(7.5-13.3)              practically non-toxic
    LD50                  A-2         4.5(3.0-6.8)               slightly toxic
    (ml/kg)               A-3        13.3(7.5-23.7)              practically non-toxic
                          A-4        12.3(8.1-18.7)              practically non-toxic
                          S-1            >25.0b                  relatively harmless
                          S-2            >25.0b                  relatively harmless
                          S-3            >25.0b                  relatively harmless
                          S-4            >25.0b                  relatively harmless
                          S-5            >25.0b                  relatively harmless
                          S-6            >25.0b                  relatively harmless
    Vapour                A-1      6 350(4 670-8 640)            slightly toxice
    exposure              A-2            >2 450b                 SVNTARTd
    LC50 in ppm           A-3             >580c                  SVNTART
    for 4 h               A-4             >553c                  SVNTART
                          S-1     73 680(66 310-79 940)          practically non-toxic
                          S-2         14 000-16 000              practically non-toxic
                          S-3          2 000-2 600               slightly toxic
                          S-4             >710                   SVNTART
                          S-5             >792                   SVNTART
                          S-6             >263                   SVNTART
    Aspiration            A-4             5/10                   hazardous
    (mortality)           S-6             5/10                   hazardous
    Primary               A-1             2.21                   moderately irritating
    skin                  A-2             2.04                   moderately irritating
    irritation            A-3             2.17                   moderately irritating
                          A-4             2.79                   moderately irritating
                          S-1             1.92                   slightly irritating
                          S-2             1.13                   slightly irritating
                          S-3             2.38                   moderately irritating
                          S-4             1.04                   slightly irritating
                          S-5             1.29                   slightly irritating
                          S-6             0.75                   minimally irritating
    Eye                   A-1             6.33                   moderately irritating
    irritation            A-2              6.0                   moderately irritating
                          A-3             4.33                   moderately irritating
                          A-4             3.67                   slightly irritating
                          S-1             0.33                   minimally irritating
                          S-2              1.0                   minimally irritating
                          S-3              2.0                   minimally irritating
                          S-4               0                    minimally irritating
                          S-5               0                    minimally irritating
                          S-6               0                    minimally irritating

    TABLE 5. (contd).

    Test                 Sample         Result                   Classification

    4-h                   A-1          approx. 5.0               practically non-toxic
    percutaneous          A-2          approx. 5.0               practically non-toxic
    LD50 rangefind        A-3          approx. 5.0               practically non-toxic
    (ml/kg)               A-4          approx. 5.0               practically non-toxic
                          S-1             >5.0                   practically non-toxic
                          S-2             >5.0                   practically non-toxice
                          S-3             >5.0                   practically non-toxice
                          S-4          approx. 5.0               practically non-toxice
                          S-5              5.0                   practically non-toxice
                          S-6              5.0                   practically non-toxice
    Repeated            benzene            3.6
    skin                toluene            3.5
    irritationf            A-1              3.3

    a   From: Hine & Zuidema (1970).
    b   Doses above this amount not practical for testing.
    c   Maximum concentration obtainable at 25 °C.
    d   SVNTART = Saturated vapours not toxic at room temperature.
    e   Lowest toxicity classification may be "relatively harmless"
    f   Scored according to the method of Draize.

        The greatest health hazard arises when hydrocarbon solvents are 
    aspirated into the lungs. This rapidly induces acute chemical
    pneumonitis, which is characterized by pulmonary oedema and
    haemorrhage, and is generally fatal (Waring, 1933; Lesser et al.,
    1943; Gerarde, 1959). Gerarde (1959) demonstrated that the ratio of
    the oral and intratracheal LD50s was 140:1 for kerosene, the
    intra-tracheal LD50 being 0.2 ml for rats. This and other evidence
    demonstrated that pulmonary injury was caused by direct contact with
    the solvent and not by solvent present in the blood, following its
    absorption through the gastrointestinal tract.

        TABLE 6.  Toxicity of solventsa

    Coined      Boiling       Compositionb      Major                  4-8h LC50c          13-wk Inhalation         Human data       Recommended
    name        range °C             %          Constituents           mg/litre (ppm)      NEL mg/litre (ppm)                        hygiene
                                                carbon                                                        Odour       Sensory    limit
                           P      N      A      number        rat      dog      cat        rat     dog        threshold   threshold  mg/litre
                                                                                                              mg/m3       mg/litre   (ppm)
                                                                                                              (ppm)       (ppm)

    V.M. & P.   118-151    55.4   32.7   11.9   C-7 to C-10   16       >8       >19        2.8     2.8        0.7-7       2.1           2.0
    Naphtha                                                   (3400)   (>1700)  (>4100)    (600)   (800)      (0.15- 1.5) (450)        (430)
    Stoddard    153-194    47.7   37.6   14.7   C-8 to C-12   >8.2     >2.9     > 10       1.1     1.9        0.5 - 5     7.85         1.15
    solvent                                                   (>1400)  (>510)   (>1700)    (190)   (330)      (09-.9)     (>150)       (200)
    Rubber      75-112     41.4   53.6    4.9   C-6 to C-7    61       >5.9     >49        7.9     7.9        40          1.7           1.7
    solvent                                                   (15000)  (>1500)  (>12000)   (2000)  (2000)     (10)        (430)        (430)
    Mixed       138-141       -      -    100   C-8           29       >5.4     <41        3.5     3.5        0.6-6       >0.46        0.46
    xylenes                                                   (6700)   (>1200)  (<9500)    (810)   (180)      (.14-1.4    (>110)       (110)
    '60'        128-159   c28.8  c21.4  c49.5   C-8 to C-9    24       >9.5     <20        0.44    1.4        10          C. 1.3       0.44
    Solvent                                                   (4900)   (>1900)  (<4100)    (90)    (280)      (2)         (260)        (90)
    '70'        157-211    16.5   15.7   67.8   C-9 to C-11   >4.4     >2.4     >2         1.1     1.1        4           0.32         0.32
    Solvent                                                   (>810)   (>440)   (>370)     (200)   (200)      (0.7)       (59)         (59)
    '140'       184-205    60.8   35.7    3.4   C-5 to C-12   >0.27    >0.21>   >          >0.23   >0.23      4           0.31         0.23
    Flash                                       (sic)         (>43)    (>33)    saturated  (>37)   (>37)      (0.6)       (49)         (37)
    aliphatic                                                                   vapour
    '80'        96-142      9.7   18.9   71.4   C-6 to C-8    27       >2.1     >24        > 1.7   > 1.7      4           0.45         0.45
    Thinner                                                   (6200)   (>480)   (>5500)    (>390)  (>390)     (0.9)       (100)        (100)
    '50'        98- 105    66.3    0.6   33.1   C-7           33       >3.4     >30        2.4     2.4        10          1.7           1.7
    Thinner                                                   (8300)   (>600)   (>7600)    (600)   (600)      (2.5)       (430)        (430)
    Deodorised  208-272    55.2  40.~9    3.9   not stated    >0.1     This value applies for all toxicity evaluation and is             0.1
    kerosene                                    probably      (14)     a saturated atmosphere at room temperature.                      (14)
                                                C 12 to

    TABLE 6. (contd)

    Coined       Boiling       Compositionb      Major                  4-8h LC50c          13-wk Inhalation        Human data       Recommended
    name         range °C             %          Constituents           mg/litre (ppm)      NEL mg/litre (ppm)                       hygiene
                                                 carbon                                                        Odour      Sensory    limit
                            P      N      A      number        rat      dog      cat        rat     dog        threshold  threshold  mg/litre
                                                                                                               mg/m3      mg/litre   (ppm)
                                                                                                               (ppm)      (ppm)

    '40'         187-231    35.4   32.9   31.5   C-9 to C-13   >0.2     >0.25    >7         0.22    0,22       1          0.21         0.15
    Thinner                                                    (>33)    (>41)    (aerosol)  (36)    (36)       (0.17)     (35)         (25)
    Toluene      95-110     38.7   15.4   45.9   C-6 to C-7    35       >3       >31        3.9     3.9        10         1.9           1.9
    concentrate                                                (8800)   (>760)   (>7800)    (980)   (980)      (2.5)      (480)        (480)
    'High        184-206     0.3    0.8   98.9   C-9 to C-12   >0.38    This value applies for all animal       0.4        0.15         0.15
    aromatic                                                   (>66)    toxicity evaluations and is a           (0.07)     (26)         (26)
    solvent                                                             saturated atmosphere at room temperature
    'High       157- 183    29.0   69.9    1.1   not stated    5.3      3.8      -          2.1     -          -          -             2.1
    naphthenic                                   probably      (960)    (>690)              (380)                                      (380)
    solvent'                                     C-9 to
    'Naphthenic  151-200    24.7   37.2   38.1   C-9 to C-11   >10      -        -          2.2     -          -          -             2.2
    aromatic                                                            (some               (380)                                      (380)
    solvent'                                                            aerosol

    a   Summary of data from Carpenter et al. (1977a,b,c).
    b   p = paraffins, N = naphthenes, A = aromatic compounds.
    c   For details of actual length of LC50 exposure, see original papers.
    d   NEL/No-ill effect/exposures 6th/day, 5 days/week for 13 weeks.


        The same author found that viscosity appeared to be the property
    that determined the aspiration hazard of liquid hydrocarbons.
    Lower-boiling-point solvents (B.P. up to 100°C) evaporated so rapidly
    in the mouth of anaesthetized rats that death was due to CNS
    depression following absorption of the vapours. Higher-boiling-point
    solvents tended to induce chemical aspiration pneumonitis. With
    alkanes, the aspiration hazard decreased sharply with solvents
    containing 16 or more carbon atoms, probably because the viscosity of
    such solvents prevented aspiration into the alveoli. In the aromatic
    series, side-chains containing more than 6 carbon atoms also tended to
    diminish the aspiration hazard, as did blending with more viscous
    lubricants (Gerarde, 1963).

    3.6.2  Long-term exposure

        The repeated skin tests of Hoekstra & Phillips (1963) and Hine &
    Zuidema (1970) have already been mentioned in section 3.6.1.

        Smyth & Smyth (1928) exposed guineapigs for 4 h/day, 6 days/
    week, for a total of 65 exposures to a gasoline-type solvent
    (boiling-range 145-183°C) at a concentration of 6750 mg/m3. During
    the earlier exposures, the animals appeared to be restless. This was
    followed by slight narcotic effects. Diarrhoea and albuminuria
    developed temporarily, but blood, lung, and other changes were absent.

        In a recent series of inhalation studies on various hydrocarbon
    fractions, Carpenter et al. (1977a, b, c) provided much new
    information on the toxicity of a wide range of solvents. Physical
    properties and the general chemical constitution are detailed in the
    papers and the approximate compositions are given in Table 6. The
    no-observed-adverse-effect levels of individual solvents following
    inhalation studies over 13 weeks in rats and dogs is also tabulated,
    together with the human sensory response (section In
    general, these studies were remarkable in the lack of toxicity that
    they indicated. The few toxic effects that did occur, were usually
    kidney damage in rats and minor haematological variations.

        Other long-term animal studies have been carried out with the
    lower-boiling fractions and more specifically with technical hexane
    and technical heptane, because of their possible neurotoxic effects
    and to establish a safe level of industrial exposure (TLV).

        Mature female Wistar rats were exposed to petroleum solvent
    vapour (physicochemical properties not given) at a concentration of
    300 ± 8.2 mg/m3 for 30-45 days, for 4 h/day. The serotonin content of
    the myometrium in exposed rats equalled 75.7 ± 2.6 µg/kg compared with
    68.47 ± 2.5 µg/kg in the control group. Uterine contractions were more
    numerous and stronger in exposed animals. The level of solvent in the
    venous blood was 2.0 ± 0.4 mg/litre. In the uterine tissues it was
    almost twice as high (3.8 ± 0.6 mg/kg). The increase in serotonin
    content in the organism could cause disturbances in the transport of
    the fertilized egg cell and the nidation, and subsequently, early
    abortion (Lipovskij, 1978).

        Miyagaki (1967) exposed 5 groups of 10 male mice to vapour
    concentrations of technical hexane of 360, 900, 1800, 3600, and
    7200 mg/m3. There was a sixth control group. The exposures lasted
    24 h/day, 6 days/week, over a period of one year. The composition of
    the hexane used is uncertain. The measured vapour concentrations
    correlated well with those calculated. Electromyographical studies
    were carried out and strength-duration curves, electrical reaction
    time, flexor/extensor ratios, and gait-posture were observed. The
    muscular atrophy of the hind legs was measured and in some of the
    animals, histological examination of the distal mucles of the hind
    legs was carried out. Evidence of neurogenic muscular atrophy was only
    seen in the group receiving the highest exposure. At the lowest
    exposure level (360 mg/m3), no changes were found in any of the
    variables studied. At the other levels, changes were found related to
    the severity and duration of exposure. Based on their results, the
    authors proposed a reduction in the TLV to 360 mg/m3.

        In a different study, which included a group of 5 rats (sex and
    age not stated) exposed to a hexane concentration of 3060 mg/m3, over
    a period of 143 days (no other details given) and a control group, no
    significant differences were found in average body weights and blood
    values (haematocrit, total serum protein, and protein fractions)
    between treated and control animals. Histological examination of
    "many" organs revealed only a "slight reaction of the RES in the
    spleen" in the exposed animals. In the sciatic nerve and its
    ramifications, injuries such as degeneration of myelin and axon
    cylinders were seen. The myoneural junction remained unaffected. The
    exposed group manifested some decrease in nocturnal activity (Kurita,

        Truhaut et al. (1973) published the results of
    electrophysiological studies on rats exposed to technical hexane or
    technical heptane. The air concentration of hexane was 7200 ±
    720 mg/m3 and that of heptane, 6000 ± 600 mg/m3 (calculated and
    expressed as  n-hexane and  n-heptane). The duration of exposure was
    5 h/day, 5 days/week for 1-6 months. The initial weight of the male
    and female rats was 150g. No data on the growth-weight curves were
    included. The composition of technical hexane was given as:

     n-pentane                              0.3%
    methyl-2-pentane and cyclopentane     25.1%
    methyl-3-pentane                      18.4%
     n-hexane                              45.8%
    methylcyclopentane                     8  %
    methylhexanes                          1.2%
    benzene                                1.2%

    and that of technical heptane as:

    methyl-2-hexane plus dimethyl 2,3 pentane plus cyclohexane        9.8%
    methyl-3-hexane                                                  16.2%
     n-heptane                                                        52.4%
    dimethyl 2,4 hexane plus methylcyclohexane                       15.4%
    methylheptane                                                     3.3%
    benzene                                                           0.1%
    toluene                                                           2.8%

        Electrophysiological studies were carried out on isolated sciatic
    and saphenous nerves taken from anaesthetized rats. During the first 2
    months of exposure, no changes were found in any of the treatments
    but, in the succeeding months, symptoms of neural involvement were
    detected, in general, increasing with the duration of exposure. The
    signs were: decrease in conduction-velocity, increase in refractory
    period, and decrease in excitability. Histopathological examination
    did not reveal clear-cut demyelination, but early indications of this
    type of change were certainly found. Truhaut has recently cast doubt
    on these findings, stating that his experimental method was not
    sufficiently rigorous to allow his earlier conclusions to be made
    (Truhaut, 1978).

        Numerous studies on the neuropathological effects of  n-hexane
    have been published including a review by Schaumburg & Spencer (1976).
    Rats exposed for 24 h/day to an  n-hexane concentration of
    1440-2160 mg/m3 for about 20 weeks developed peripheral neuropathy.
    Toxicity data on the presumptive  in vivo neurotoxic oxidation
    products of  n-hexane have also been published (Spencer et al.,
    1978). It should be mentioned that many authors have used the term
    " n-hexane" loosely; the tested material often really consisted of
    various C-6 hydrocarbons.

        Some other hydrocarbon solvents have been implicated as possibly
    causing neuropathy, following prolonged exposure to high
    concentrations. As these reports are generally related to human
    exposure, they will be considered in section Of relevance is
    the observation that toluene inhaled by rats over a period of one year
    induced electrophysiological changes at concentrations of 7500 mg/m3
    and 750 mg/m3 but not at 375 mg/m3 (Matsumoto, 1971). Fournas & Hine
    (1958) exposed rats to high concentrations of various alkyl aromatic
    hydrocarbons and found some clinical evidence of neurotoxicity with
    most of the compounds tested;  p-t-butyltoluene was shown to induce
    CNS damage in rats by Ungar et al. (1955).

    3.6.3  Mutagenicity, teratogenicity, and carcinogenicity  Mutagenicity

        The potential mutagenic activity of selected petroleum products
    was assessed using a battery of  in vivo and  in vitro bioassays,
    including the dominant lethal test, the Ames' test (with and without
    activation), the mouse lymphoma cell transformation test, and
    observations on cytogenicity. The following products elicited negative
    responses in one or more tests: VM&P Naphtha, Stoddard Solvent, mixed
    xylenes, "60 Solvent", "70 Solvent", 140° Flash Aliphatic Solvent, "50
    Thinner", kerosene, toluene, high solvency naphtha- unleaded petrol,
    and No. 2 heating oil (40% aromatic compounds). Positive mouse
    lumphoma cell transformation tests were elicited by benzene, diesel
    fuel, No. 2 heating oil, and jet A fuel; positive results in
    cytogenetic tests (clastogenic responses) were obtained with rubber
    solvents, "60 Solvent", high aromatic solvent, No. 2 heating oil, and
    jet A fuel. For each of these products the Ames bacterial bioassay was
    negative (API, 1974, 1975b, c, 1977a, 1978a, d, f, 1979d).  Teratogenicity

        Tests for teratogenicity induced by inhalation of high and low
    doses of benzene, Stoddard Solvent, toluene, mixed xylenes, unleaded
    petrol, high aromatic solvent,  n-hexane, diesel fuel, VM&P naphtha,
    kerosene, rubber solvent, jet fuel A, and No. 2 heating oil were all
    negative. However, benzene exposure at 120 mg/m3 induced a
    statistically significant increase in fetal resorptions in rats (API,
    1974, 1975a, b, c, 1977 a, b, 1978a-f, 1979a-d).  Carcinogenicity

        Carcinogenicity tests have only been conducted on the group of
    high-boiling aromatic extracts derived from the solvent refining of
    lubricating base oils. These studies will be considered together with

    long-term studies on lubricating base oils, but, in short, practically
    the whole of the carcinogenic polynuclear aromatic hydrocarbons were
    found in the extracts from the base oils. However, the carcinogenic
    activity of the extracts was considerably less than that of
    coal-tar-derived products.

        Similar carcinogenicity studies have not been carried out with
    the lower boiling aromatic solvents (white spirits). Such studies
    would be indicated, though the content of potentially carcinogenic 4,
    5 and 6 condensed ring polynuclear aromatic hydrocarbons in these
    aromatic solvents is probably much lower than in high boiling aromatic
    solvents, because of the lower boiling range. Lijinsky & Raha (1961)
    mention, however, that no commercial distillation procedure will
    completely remove all traces of polynuclear aromatic hydrocarbons from
    petroleum solvents and that special treatment is necessary to achieve
    this. Though, in most cases, the authors found very low concentrations
    (in the µg/m3-range), they are of the opinion that these levels
    should be investigated, particularly in food-grade material.

    3.7  Effects on Man

    3.7.1  Controlled exposures  Effects of dermal exposure

        Klauder & Brille (1947) patch-tested petroleum solvents of
    various boiling ranges on the skin of human volunteers. They found a
    correlation between the boiling ranges of the petroleum products of
    paraffinic origin and their irritant and defatting action on the skin.
    Both effects decreased, the higher the boiling range. Petroleum
    solvents with boiling ranges up to and including that of kerosene
    (approximately 230°C) were found to be primary irritants. Petroleum
    solvents of naphthenic origin or with a high aromatic content were
    more irritant than solvents of paraffinic origin of the same boiling
    range. The skin of Negroes showed a higher tolerance than that of

        Pre-existing skin disease may increase the susceptibility of the
    skin to the effects of contact with petroleum solvents and will also
    facilitate uptake by this route (Klauder & Brille, 1947; Riihimäki &
    Pfäffli, 1978).

        The effects of various solvents on the horny layer of the skin
    were examined by Malten et al. (1968) and Spruit et al. (1970). They
    found that petroleum ether (SBP 40/65) caused serious irritation of
    human forearm skin, when applied for periods of 10-30 min. When
    applied for 15 min on 6 successive days, injury occurred in the horny
    layer. Recovery -- as measured by water vapour loss -- could take up
    to 6 weeks. The skin irritation and the changes in the composition of
    the horny layer were independent phenomena.

        Tagami & Ogino (1973) applied undiluted refined kerosene to the
    arm of a volunteer in an occluded patch-test. After 1 h, a burning
    sensation developed, slight erythema appeared after 2 h, and after
    7 h, the skin was tender and very red, even beyond the patch-test
    site. After 12 h, the burning sensation had subsided but a large tense
    bulla had appeared surrounded by small scattered vesicles. This
    changed into a large flaccid purulent bulla 24 h later, which easily
    broke, leaving a raw surface. The main differences between the test
    situations just described were:  (a) a marked difference in boiling
    range (volatility and skin penetration) of the products tested; and
     (b) the length of exposure, the effect increasing with increasing
    duration of exposure.

        The same authors then applied 85%, 70%, 55%, and 40% dilutions of
    the kerosene in mineral oil in covered skin test on 34-adult male
    Negro and Caucasian volunteers. The skin of all the subjects reacted
    to 85% kerosene solution, the 70% solution caused skin irritation in
    29 subjects, the 55% solution in 8, and the 40% solution was
    completely without effect. The skin of Negroes appeared to be less
    irritated by kerosene than that of Caucasians; the influence of age
    was not clear. No definite correlation was found between individual
    response to kerosene and the permeability of the horny layer of the
    skin (Tagami & Ogino, 1973).  Effects of inhalation

        Inhalation of air containing petrol at concentrations of
    1350-3150 mg/m3 for 18 min by human volunteers did not cause any
    symptoms; a 14-min exposure to 12 600-31 500 mg/m3 induced dizziness
    (Fieldner et al., 1921). Davis et al. (1960) exposed human volunteers
    for 30 min to concentrations of petrol of 900, 2250, or 4500 mg/m3 in
    air. Very few symptoms were noted. Itching and burning of the eyes was
    apparent in most subjects in the highest exposure group.

        The human odour- and sensory irritation thresholds were measured
    as part of the toxicity evaluation of solvents carried out by
    Carpenter et al. (1977a) (Table 6). It can be seen that vapours of
    hydrocarbon solvents can be detected at rather low concentrations, but
    that unpleasant odour and irritation only become apparent at much
    higher concentrations. Nevertheless, in establishing an exposure limit
    for each solvent, human sensory data were often limiting factors.

        In volunteer studies, psychological functions were affected by a
    50-min exposure to a concentration of white spirit of 4000 mg/m3
    resulting in a prolonged reaction time and impaired short-term memory.
    Lower concentrations did not have any effect (Gamberale et al., 1975).

    3.7.2  Epidemiological studies

        A distinction between epidemiological and clinical studies has
    always been difficult in view of the inadequacy of reporting. The
    various aspects will therefore be discussed under headings relevant to
    the information available.  Occupational exposure

    (a) Haematological effects

        Benzene is unquestionably the most dangerous hydrocarbon used in
    industry and the benzene content of some petroleum solvents presents a
    major long-term hazard for man. In particular, special boiling
    solvents in the lower-boiling range may contain a considerable
    percentage of benzene (Gerarde, 1960). In this review, it is
    impossible to consider in detail the effects of benzene, which
    basically causes bone-marrow depression and has a leukaemogenic
    action. Excellent reports on all aspects of benzene toxicity can be
    found in: ILO (1968); Deutsche Forschungsgemeinschaft (1970); IARC
    (1974); and Laskin & Goldstein (1977).

        In the past, benzene-like effects have also been ascribed to
    other low-boiling petroleum solvents. However, there now seems to be
    general agreement that these effects only occur, when benzene is
    present in the mixture (Browning, 1959, 1965).

    (b) Neuropathological effects

        The neuropathological effects of inhalation of petroleum solvents
    in man have been discussed in a number of reviews including those of
    Cavanagh (1973), Allen (1975), Seppäläinen (1975), Comstock (1977),
    and Savolainen (1977). The reviews include discussions of methods used
    to evaluate human neuropathy.

        Over the past 15 years, an increasing number of cases of
    poly-neuropathy and other neurotoxic effects have been described in
    workers exposed to hydrocarbon solvents. Many of these cases have been
    associated with prolonged and repeated exposure to high concentrations
    of  n-hexane. Frequently, such exposure has resulted from poor
    ventilation in a workroom in which solvents containing high
    concentrations of hexane have been used. Miyagaki (1967) reported
    hexane concentrations in air of 1800-3600 mg/m3 in the workroom and
    7200 mg/m3 near the source in a work-place where 17 cases of
    peripheral neuropathy occurred. Yamamura (1967) and Inoue et al.
    (1970) found concentrations ranging from 1800-9000 mg/m3 in a work
    place where, over a 9-year period, 93 out of the 1662 workers suffered

    from polyneuritis. These workers used glue in the manufacture of vinyl
    sandals for 8-14 h daily, probably for more than 5 days each week,
    over long periods, in poorly ventilated rooms. The presence of hexane
    in glues is reported to have caused similar incidents in Italy and
    Iran (Capellini et al., 1968; Scrima & de Rosa, 1973; Ghazai, 1974).
    In most cases, the extent of exposure to hexane was uncertain, either
    because air concentrations were not measured or because excessive skin
    contamination occurred; workers frequently handled the glues and
    washed residues off the skin with hexane-containing solvents. In other
    cases, air concentrations were measured. Hexane concentrations of
    approximately 2340 mg/m3 (but at times up to 4680 mg/m3) were found
    in a small, poorly ventilated workroom in which 3 women, who developed
    polyneuropathy, had worked; again excessive skin contact took place
    (Herskowitz et al, 1971; Ishii et al., 1972). Glue was also the source
    of hexane concentrations of 1000-4000 mg/m3 found by Paulson &
    Waylonis (1976) in the air of a work-place where 8 out of 50 employees
    developed mild neuropathy.

        The main clinical manifestation in these cases was polyneuropathy
    of the glove-and-stocking type with sensations of numbness and cold.
    This was accompanied by muscular weakness and headaches. Gradual
    recovery was usual, when exposure ceased, with the exception of some
    subjects who had severe muscular atrophy. Peripheral nerve biopsy
    showed demyelination with relative preservation of the axon. Iida
    et al. (1969) reported that in 44 cases there was a reasonable, but
    not exact, correlation between clinical findings and electromyography
    and nerve conduction velocity data.

        Optic involvement was observed by Inoue et al. (1970). The
    neuro-ophthalmological function was studied by Raitta et al. (1978) in
    15 workers who had been exposed at work over periods of 5-21 years to
    hexane concentrations of 1800-3600 mg/m3, with occasional levels of
    10 800 mg/m3. Defective colour discrimination was found in 12 of the
    workers and slight macular changes in 11 out of 15. The visually
    evoked potentials and electroretinograms were interpreted by
    Seppäläinen et al. (1979) as indicating cerebral dysfunction, probably
    a conduction block in intracerebral axons.

        Polyneuropathy attributable to the inhalation of hexane has also
    been observed in "glue sniffers" -- subjects who inhale solvent
    vapours to induce elation or other states of mind. Cases including
    very rare cases following medicinal use, were described by Schwarz
    (1933), Browning (1965), Karani (1966), Gonzales & Downey (1972),
    Matsumura et al. (1972), Taher et al. (1974) and Korobkin et al.
    (1975). Other incidents have been reported or reviewed by Shirabe et
    al. (1974), and Poklis & Burkett (1977). While hexane appears to have
    played a major role, a direct or synergistic action of other
    components cannot be ruled out.

        Some cases have been described that were thought to arise from
    the long-term, continuous domestic use of kerosene stoves in poorly
    ventilated rooms (Contamin et al., 1960). Under simulated conditions,
    hexane concentrations of about 1440 mg/m3 were produced in
    experimental rooms by Lièvre et al. (1967).

        The possibility of the production of peripheral neuropathy by
    components other than hexane, or the intensification of the activity
    of hexane, is suggested by some clinical reports. Cargill (1972)
    (cited by Gaultier et al., 1973) described peripheral neuritis in
    workers using glue containing cyclohexane, gasoline "c", and methyl
    ketone, and Franco et al. (1979) reported sensory and peripheral motor
    conduction disturbances, where exposure to cyclohexane had occurred.
    The condition was described by Gaultier et al. (1973) in subjects who
    had been in prolonged contact with a glue solvent containing 80%
    pentane, 5% hexane, and 14% heptane. Gasoline concentrations of
    2250 mg/m3 were found in the workshop atmosphere. Atmospheric
    gasoline concentrations of up to 5625 mg/m3 (mainly  n-pentane,
     n-hexane, and  n-heptane) were found in workshops where workers had
    developed polyneuropathy and had complained of insomnia, irritability,
    and other non-specific CNS symptoms. White spirit has also been
    implicated as a cause of peripheral neuropathy (Gaultier et al.,
    1973). Heavy exposure to jet fuel vapours was reported in workers who
    experienced dizziness, palpitations, nausea, and headaches, later
    followed by signs and symptoms of polyneuropathy; higher vibration
    thresholds, compared with unexposed controls were also found. (Knave
    et al., 1976).

        Other symptoms besides those of polyneuropathy have been
    described in subjects exposed to hydrocarbon solvents. Sterner (1941)
    reported headaches, nausea, mental depression, anorexia, inability to
    concentrate and sustain activity, and slight anaemia, in workers
    exposed to gasoline vapours (used to dilute spray paint) containing
    5-10% aromatic hydrocarbons and producing concentrations of total
    aromatic hydrocarbons in air of 300-800 ppma. Knave et al. (1978)
    compared 30 workers, occupationally exposed to jet fuel, with
    unexposed controls. The average period of exposure was 17 years and
    the estimated TWA exposure was 300 mg/m3. Significant differences
    were found between exposed and unexposed groups in the incidence and
    prevalence of psychiatric symptoms, psychological test results,
    especially attention and sensorimotor speed, and in
    electroencephalograms. Exposure of car painters, over many years, to
    low concentrations (31.8% of the Finnish TLV on average) of solvent
    mixtures containing toluene, xylene, butyl acetate, and "white

    spirit", was found to be associated with an increased incidence of
    sleep disturbance, absentmindedness, falling asleep while watching the
    television, and headaches. Lower peripheral nerve conduction
    velocities, psychomotor impairment, and personality changes were more
    common in exposed than in control subjects. Further studies are needed
    to elucidate the significance of such findings (Hänninen et al., 1976;
    Seppäläinen et al., 1978).

        In summary, the most serious adverse neurological effect of
    hydrocarbon solvents in man is the production of peripheral
    neuropathy. Observations in man and studies on experimental animals
    support the view that exposure to  n-hexane is the principal cause.
    However, the synergistic activity of other hydrocarbons is possible;
    such a phenomenon has been reported following the sniffing of a glue
    thinner containing both the neuropathic solvent, methyl- n-butyl
    ketone, and the non-neuropathic solvent, methyl ethyl ketone
    (Altenkirch et al., 1977). At present, the possibility that other
    hydrocarbons also have some neurotoxic activity cannot be ruled out.
    Peripheral neuropathy has occurred only in conditions of prolonged and
    repeated exposure to high concentrations of hydro-carbon solvent
    vapour in air; in many cases, there was also excessive skin contact.
    Atmospheric exposure levels in excess of 2 g/m3 are usually
    encountered where peripheral neuropathy is seen, but more studies are
    required to clarify the situation, and until this is done, close
    supervision is needed to ensure that the TLV for solvents is not
    exceeded. Further studies are also necessary to determine the
    significance of psychological disturbances and of neurophysiological
    findings in workers exposed to lower levels of the hydrocarbons.

    (c) Effects on reproductive functions

        Examination of 408 female workers in petroleum refineries, who
    had been subjected to long-term exposure to hydrocarbons, hydrogen
    sulfide, and other products related to the treatment of sulfurous
    crude, revealed disturbances in the menstrual function, mainly in the
    form of hypomenstruation and pre-menstrual syndromes. According to
    Suhanova & Melnikova (1974), such disturbance of the menstrual
    function in female workers in refineries and in persons suffering from
    chronic intoxication from petroleum products (36 persons in the age
    bracket 30-39 years) is caused by the hypo-functioning of the ovaries.


    a  Since the composition is not given, it is not possible to
       transform this concentration into mg/m3, the adopted SI unit.

        Beskrovnaja et al. (1979) studied the gynaecological disease rate
    in more than 5000 female operators in plants producing rubber articles
    (petroleum solvent vapour concentration in the air of 250-350 mg/m3).
    They observed disturbances in the menstrual cycle in workers with more
    than 5 years' service and a high frequency of metrorrhagia. As the
    period of service increased, a reduction in the frequency of
    miscarriages was noticed, which was interpreted by the authors as
    possible adaptation. A disturbance of the ovarian function was noted
    in 24.4% of the workers examined, mostly in the form of a functional
    deficiency of corpus luteum.

        Investigations of vaginal smears of 184 female gluers in the
    rubber industry in the age bracket 18-38 years revealed a disturbance
    of the ovarian function with reduced estrogen stimulation in 21.7% of
    the women (10.4% in the control group). This figure was related to the
    period of service. After 10 years service, the percentage was twice as
    high as after 5 years' service.

        Women who had been in contact with petroleum solvents were found
    to have a reduced estrogen level in the blood (22.2 µg/day compared
    with 29.6 µg/day in the control group). Essentially, no changes were
    observed in the excretion of the follicle-stimulating and luteinizing
    hormone pregnanediol. The authors of this study assumed that the
    sensitivity of the ovaries towards the stimulating effect of the
    gonadotrophins was reduced (Hrustaleva et al., 1979).

        Novikov et. al. (1979) studied lactation in 332 nursing mothers
    288 of whom worked in the rubber industry (vulcanizers, pressers,
    gluers). The concentration of petroleum solvents (the physico-chemical
    properties of which are not described) in the air of the operating
    premises was predominantly 300 mg/m3. Hypolactation, found in 23.8%
    of the women compared with 6.7% in the control group was related to
    length of service. Hydrocarbon solvents were found in the milk of all
    the persons examined (71) in concentrations of 0.50 ± 0.05 mg to
    0.60 ± 0.09 mg/litre. The serotonin content of the blood of these
    women was significantly lower than in the control group. It is assumed
    that hypolactation was the result of the effect of solvents on the
    lactation control mechanism via the hypothalamus and the
    serotoninergic system.

    (d) Effects on the skin

        Skin can also be affected by exposure to solvents. In a study on
    skin conditions and other diseases in 54 gasoline and diesel station
    workers, skin conditions related to exposure to gasoline and diesel
    fuel were minimal and did not interfere with capacity to work. Only
    dryness, chapping, and reddening of the skin were found. The dark skin
    of Indonesians seemed to be more resistant to these effects. The
    gasoline vapour in the working environment caused some non-specific
    symptoms in addition to those resulting from heavy out-door work
    (Suma'mur & Susianti Wenas, 1979).  General population exposure

        Data are not available concerning the exposure of the general
    population to petroleum solvents with the exception of that of
    "sniffers" and addicts already mentioned in section

    3.7.3  Clinical studies

        It should be noted that literature surveys of clinical studies
    and clinical effects have been published by Gerarde (1960), Browning
    (1965), and Levina (1976).  Effects of dermal exposure

        In general, petroleum solvents have a defatting action on the
    skin and, on repeated contact, cause injury to the horny layer
    (section This makes the skin more susceptible to other
    irritants, sensitizing agents, and bacteria. It may also result in
    progressive dermatitis, characterized successively by dryness,
    redness, chapping and scaling, which could lead, by sensitization, to
    eczema. These stages of dermatitis may be seen in workers in garages
    or automobile repair shops, who wash their hands with solvents, petrol
    or kerosene (Tagami & Ogino 1973). The more aromatic solvents, in
    particular, can cause a significant degree of primary skin irritation.
    The defatting action and primary irritation caused by petroleum
    solvents decrease, the higher the boiling range section 3.6.1).

        Cases in which gasoline or kerosene remains in contact with the
    skin for prolonged periods mainly occur in children or in unconscious
    accident-cases, when clothing has become soaked with the solvent. In
    such cases, the lesions start with a burning sensation and erythema,
    followed by the formation of small or large vesicles, blisters, or
    even extensive epidermolysis. The vesicles and blisters may become
    mucopurulent in a few days. The acute picture is that of a chemical
    burn, (Helbling, 1950; Aidin, 1958; Ainsworth, 1960; Stewart, 1960;
    Browning, 1965; Hunter, 1968; Tagami & Ogino 1973).

        Gasoline may occasionally be absorbed through the skin in toxic
    quantities if large areas of skin such as the hands and forearms are
    regularly exposed (Hayhurst, 1936), or in cases of extensive
    epidermolysis in contact with gasoline-soaked clothing. However
    inhalation of vapour plays a significant additional role in all these
    cases and generally is the main route of absorption (Browning, 1965).  Effects of inhalation

        The acute effect of massive overexposure to gasoline vapour is
    mainly narcosis with loss of consciousness and possibly convulsions,
    which may be fatal (Browning, 1965). Octane causes rapid and deep
    narcosis, pentane and hexane are less powerful narcotics, but they and
    heptane exert a paralytic effect on the central nervous system and its
    respiratory centre.

        In more gradual overexposure, the symptoms just described may be
    preceded by eye irritation, irritation of the respiratory tract,
    dizziness, headache, and a sense of drunkenness.

        A gasoline concentration of 9000 mg/m3 can be breathed without
    significant ill-effects by most people but susceptible subjects may
    show symptoms after exposure to 1350-2250 mg/m3 (Ainsworth, 1960). At
    31 500 mg/m3, dizziness and symptoms of drunkenness may appear.
    Exposures in excess of 45 000 mg/m3 soon become intolerable and may
    rapidly prove fatal (Machle, 1941, Aidin, 1958). Lower and higher
    values have been quoted, obviously depending on the composition of the
    gasoline (Browning, 1965). The margin of safety between narcosis and
    respiratory arrest is very narrow in exposures to high concentrations
    of gasoline (Wang, 1961).

        Absorption of gasoline vapour by inhalation may be very rapid if
    the concentration is high, especially with the lower members of the
    paraffinic range, and symptoms can appear within a few minutes.
    Excretion, probably of unchanged vapours, takes place mainly via the
    lungs (Browning, 1965).

        Acute occupational poisoning by gasoline vapour is mostly caused
    by entering unpurged gasoline tanks or other premises where high
    concentrations of gasoline may have accumulated. Exposure to high
    concentrations may also occur in car accidents, when victims are
    trapped and/or unconscious.

        Histopathological changes found in subjects who have died after
    exposure to high concentrations of gasoline vapour include: hyperaemia
    and petechial haemorrhages in the lungs, and, sometimes, necrosis of
    the alveolar walls. There may be haemorrhages or effusions in internal
    organs and serous cavities (Helbling, 1950; Ainsworth, 1960; Browning,
    1965). Liver and kidney may show fatty degeneration. Hyperaemia and
    oedema of the brain are common in this condition and myelin swelling
    may occur (Machle, 1941).

        Long-term exposure to low (unspecified) vapour concentrations may
    cause nonspecific symptoms of the nervous system and digestive tract
    (Zielhuis, 1961; Browning, 1965; Muhametova & Podrez, 1975; Sehtman et
    al., 1979), including changes in liver function and in the visual
    organ. In women, the reproductive organs may be affected (Muhametova &
    Podrez, 1975; Sehtman et al., 1979). Neurological disturbances, as
    described in section may develop (Hayhurst, 1936; Machle,
    1941; Browning, 1965). Browning (1965) considered that significant
    changes observed in the blood count were caused by the presence of
    benzene in the solvent.

        This chronic form of toxicity may be found in small,
    insufficiently ventilated workshops where solvents, or products
    containing them, are handled in an unsatisfactory way (section and when these materials are used in substantial amounts in
    enclosed spaces, particularly for cleaning or degreasing (Anon.,
    1974).  Effects of ingestion

        Accidental ingestion of petroleum distillates in the range of
    petroleum solvents is an important cause of poisoning in children
    (Waring, 1933; Nunn & Martin, 1934; Lesser et al., 1943; Carithers,
    1955; Daeschner et al., 1957; Gerarde, 1959, 1963). Most cases,
    however, are caused by gasoline and kerosene and fewer by petroleum
    solvents. The symptomatology is the same in all cases.

        Coughing, choking, and gagging are often noted at the time of
    ingestion of these substances. Respiratory embarrassment may be
    present early, indicating that aspiration has taken place. Epigastric
    discomfort may develop, followed by vomiting with a further risk of
    aspiration. Aspiration by one mechanism or another is reported to
    occur in up to 95% of cases in children, but this depends on the
    situation and on the type (boiling-range) of the solvent involved.
    Aspiration is less common in adults, but may occur when trying to
    siphon gasoline from a tank. Small amounts of kerosene of the order of
    1-2 ml, if aspirated, can cause severe and even fatal pulmonary
    changes. On the other hand, if aspiration does not occur, much larger

    quantities can be tolerated (Daeschner et al., 1957; Hensen, 1959;
    Browning, 1965). Browning (1965) quotes a value of 7.5 g/kg body
    weight, but this may depend on the type of solvent. Children appear to
    be more susceptible to the toxic effects than adults (Siwe, 1932). In
    cases where aspiration does not take place, and especially with the
    lower-boiling solvents, central nervous system symptoms may develop
    such as lethargy, convulsions, and coma. With smaller doses, the
    symptoms include vertigo, headache, and signs of drunkenness. Nausea,
    vomiting, and diarrhoea may occur and the stools may be blood-tainted.

        In uncomplicated cases, the gastrointestinal symptoms will
    disappear within 48 h. Pulmonary symptomatology will not develop, if
    aspiration has not occurred and if there was no massive exposure to

        The syndrome of acute chemical aspiration pneumonitis will be
    described in a wider context in section 4.8. Human experience is in
    accordance with the results of experimental animal studies (section
    3.6.1). Chemical pneumonitis with pulmonary oedema and haemorrhagic
    frothy sputum may develop extremely rapidly following aspiration of
    petroleum solvents. Roentgenographic changes may be seen within a few
    hours, especially at the lung bases. Later, bacterial pneumonia can
    complicate the situation (Daeschner et al., 1957; Gerarde, 1963).

        The prognosis of aspiration of hydrocarbon solvents appears to
    have improved with better treatment in the course of time. Siwe (1932)
    reported that 50% of the cases he reported were fatal, Nunn & Martin
    (1934) reported 28% mortality following the ingestion of gasoline and
    9.2% following kerosene-ingestion, and Blattner (1951) reported that
    death resulted in 10-14% of cases of kerosene poisoning. Recently, 3
    cases have been described, where exposure to diesel oil seemed to
    cause acute renal failure with oliguria (Reidenberg et al., 1964;
    Barrientos et al., 1977; Crisp et al., 1979). However, in 2 cases,
    absorption seemed to have been mainly through the skin (section


    4.1  Properties and Analytical Methods

    4.1.1  Chemical and physical properties

        Base oils are a limited group of petroleum products in the
    boiling-range of 300-700°C, normally derived from the high-vacuum
    distillation of the residues of the crude-distilling process. These
    oils undergo a further refining process before being used.

        Lubricating oils, metal-working oils, and related products are
    produced by blending base oils in order to obtain the desired physical
    properties. Chemical additives are frequently added, usually in small
    amounts (a few mg to a few g/kg) to improve the performance of the
    lubricant. In some special cases, higher concentrations are necessary.
    Additives belong to the following general categories: viscosity-index
    improver, emulsifiers, wetting agents, antioxidants, dispersants,
    antiwear additives, extreme pressure additives, rust-inhibitors,
    antifoam agents, pourpoint depressants, and germicides.

        Greases based on mineral oil consist of solid or semisolid
    dispersions of metallic soaps and other thickeners in a mineral oil

        Petroleum waxes are crystalline solids at normal temperature.
    "Slack wax", a soft, impure paraffin-wax is obtained in the
    manufacture of lubricating base oils from paraffinic crude oils by a
    dewaxing process. Slack wax can be refined into 2 types of commercial
    wax: paraffin wax and microcrystalline wax.

        Base oils are very complex mixtures of hundreds to thousands of
    different hydrocarbons, containing straight-chain and branched
    paraffins, cycloparaffins, naphthenic, aromatic, and polynuclear
    aromatic hydrocarbons in the range of C-17 and higher. The separate
    molecules are so large, that any molecule may, for instance, contain
    one or more aromatic rings with one or more long side-chains.

        The actual composition depends on the source of the crude oil,
    from which the product is derived, and the manufacturing and treating
    processes used. They range from thin, easily flowing "spindle oils" to
    thick "cylinder oils". A limited number of base oils are used for
    blending to obtain the commercial products. As the relation between
    viscosity and temperature is an important factor in this field, base
    oil grades are characterized by their viscosity and viscosity index
    (VI). The higher the viscosity index, the less the change in viscosity
    with temperature.

        Low viscosity index (LVI) oils are used whenever the viscosity
    temperature characteristics and oxidation stability are of less
    importance. In general, they are derived from naphthenic oils and
    undergo treatment with sulfuric acid and clay or are given a
    hydro-finishing treatment.

        Medium viscosity index (MVI) oils, can be used as a base for
    general-purpose lubricants. They can be derived from naphthenic (MVIN)
    or paraffinic (MVIP) feedstocks. MVIP has to be dewaxed and can also
    be solvent refined, acid- and clay-treated or hydro-treated.

        High viscosity index (HVI) oils, are prepared by both solvent
    refining and dewaxing of paraffinic feedstocks. They are used for
    gasoline and diesel engine oils and for turbine lubricants, because
    they are, in general, more oxidation-stable than other base oils and
    have appropriate viscosity/temperature characteristics.

        White oils are generally produced by more drastic refining of MVI
    oils, in order to remove unsaturated compounds, aromatic compounds,
    and other constituents that influence colour, odour, taste, and
    acceptability as food-grade material. Solvent extraction followed by
    repeated treatment with oleum and alkali is used. Hydrogenation is
    another means of producing such oils.

        Medicinal oil is the highest purified grade, which complies with
    the requirements of the various national pharmacopoeias and
    regulations on food-grade material. As liquid paraffin, the same grade
    is used as a lubricant for food-handling machines and as an ingredient
    in pharmaceutical preparations and cosmetics.

        Technical white oils, less rigidly purified than medicinal oil,
    are non-carcinogenic oils that can be used for the lubrication of
    textile machinery, spinning mules, etc., but are mainly used in the
    cosmetic industry in the manufacture of hair-oils, creams, etc.

        Aromatic extracts, which are obtained in the solvent-refining
    process, have already been discussed in section 3.1.1.

        Petroleum waxes consist essentially of high relative molecular
    mass paraffinic hydrocarbons with approximately 20-40 carbon atoms per
    molecule. Paraffin waxes consist mainly of normal paraffins together
    with some iso and cycloparaffins. They are macrocrystalline with a
    melting-point of 43-71°C.

        Microcrystalline waxes on the other hand, consist mainly of iso
    and cycloparaffins with some alkylated aromatic hydrocarbons. They are
    mostly soft materials, but may sometimes be a hard brittle solid.

        When highly purified, the colour may be white, however, it is
    usually yellow or amber, sometimes even black. The melting-point is
    60-90°C. The paraffin oil content ranges from 5 to 50 g/kg.

        Petrolatum is also known as petroleum jelly and is a
    micro-crystalline wax with a high oil content.  Purity of Product

        As these oils and waxes are complex mixtures, the nature and
    proportion of potentially undesirable "impurities" depends to a large
    extent on the definition of the term and on the degree of refining. In
    the range from the highest refined oil -- for example, white medicinal
    oil -- to the least refined oil, "impurities" could include
    polynuclear aromatic hydrocarbons and unsaturated hydrocarbon

        It is clear that highly purified products can be obtained at the
    cost of extra refining and treating processes. Paraffin waxes are an
    example of progressive refining: fully refined paraffin wax is a white
    solid material containing an oil concentration of less than 5 g/kg. It
    is odourless and tasteless and has a melting-point of 50-70°C. Candle
    waxes range from fully refined paraffin wax to less refined waxes
    containing oil levels of up to 15 g/kg. This type of wax is not
    completely colourless and odourless. Scale wax and match wax contain
    an oil residue of up to 30 g/kg.

    4.1.2  Methods of sampling and analysis

        See section 2.1.2.

    4.2  Sources of Environmental Pollution

    4.2.1  Natural occurrence

        Base oils occur in nature only as components of the crude oils
    from which they are derived.

    4.2.2  Man-made sources  Production

        As mentioned earlier, lubricating base oils are a group of
    petroleum distillates and residues in the boiling-range 300-700°C,
    derived by high-vacuum distillation of the residues obtained in crude
    oil distillation (section 4.1.1). In order to obtain base oils with
    the qualities and specifications needed for various applications,
    further refining and treatment of the various distillate fractions is
    needed. The main processes used are:

    (a) Solvent extraction

        This is a process by which aromatic hydrocarbons can be extracted
    from oil fractions, thus obtaining a low aromatic or aromatic-free
    raffinate, and a high aromatic extract. Liquid sulfur dioxide,
    sulfolane, benzene, phenol, or furfural can be used as solvents for
    this purpose. The raffinate can be used for producing a lubricating
    base oil, the extract can be used as a solvent (see under petroleum

    (b) Dewaxing process

        In this process, "slack wax" is separated (crystallized) from
    base oil fractions obtained from paraffinic crude oil residues. This
    is done by cooling, followed by filter-pressing. The separation of wax
    and oil under chilled conditions is facilitated by the addition of
    solvent. The resulting wax may still have an oil content of up to
    100-400 g/kg.

    (c) Acid treatment

        The oil is mixed with 98% sulfuric acid and the acid sludge is
    centrifuged off. This is usually followed by clay treatment in which
    the oil is mixed with absorbent clay, followed by filtration. This
    neutralizes the oil and improves colour, odour, and stability.

    (d) Hydrofinishing

        This is a catalytic hydrogen treatment at elevated temperature
    and pressure. Improved stability and colour of the oil is obtained by
    the hydrogenation of unstable compounds, which removes sulfur and
    saturated olefins, diolefins, and aromatic components.

        As the definition and classification of lubricating base oils are
    not clear, it is difficult to give precise production data for this
    group of products. The best current estimate is 35-38 million tonnes
    per year. Though there was a decrease in the annual production after
    1973, lubricant production has subsequently increased, but at a lower
    rate.  Uses

        In general, the main functions of lubricating oils and
    metal-working oils are: to reduce friction, to remove generated heat,
    to remove debris from the contact area, and to protect against
    corrosion. In addition, mineral oils are used as hydraulic media in a
    wide variety of applications. Very general remarks have already been
    made concerning the composition of, and the various additives in,

    lubrication oils, metal-working oils, and greases. The following is a
    list of the most important categories of products on the market, from
    which it is clear that the great majority are handled in industrial
    situations, and that the general population has regular contact with
    only a few such products:

    (a)  Industrial lubricating oils, which can vary from thin spindle-oil
         to the very viscous oils used in steam engines;

    (b)  Lubricants for internal combustion engines of various types;

    (c)  Crankcase, compressor, gear, and turbine oils;

    (d)  Greases for bearings and other purposes;

    (e)  Hydraulic, transformer, insulating, heat-transmission oils;

    (f)  Cooling, quenching, anticorrosion, and mould oils;

    (g)  Metal-working oils: cutting, grinding, rolling, drilling,
         drawing-oil, a multitude of products for specific purposes. They
         consist in general of complex mixtures with various additives,
         for use in the neat state and also as water extendible fluids or

    (h)  Textile oils: spindle, hatching, technical white lubricating oil;

    (i)  Process oils: used in printing-inks, as rubber extenders, and as
         technical white oils in cosmetics, etc;

    (j)  Waxes of various grades and purity;

    (k)  Medicinal white oil used for medicinal and food-grade

        The manufacturing, treating, and purification processes used in
    the preparation of the base oils vary according to the future
    application of the commercial product.

        Many of the products can undergo considerable changes during use.
    This should be borne in mind in extrapolating from used oils to the
    original product in the case of adverse health effects, e.g., in the
    case of skin sensitization. The following are a few examples of
    changes that may occur:

        (a) During use, the chemical and physical characteristics of
    lubricating oils change, mainly because of contamination, oxidation,
    and polymerization. Metal particles, airborne dust, water, and, in the
    case of internal combustion engine oils, small quantities of fuel,
    acids, and soot, are the main contaminants. All this can result in the
    formation of sludge.

        (b) Metal-working oils become contaminated in use with a wide
    variety of foreign matter, in particular metal particles (and ions).
    Water-based metal-working emulsions can also be affected by bacteria,
    yeasts, and fungi. Oxidation and heat cracking may occur at the
    application point, causing smoke, steam, and oil mist to be emitted
    into the working environment. Nitrite may be added to most water-based
    cutting oils, thus these sometimes contain carcinogenic nitrosamines
    (Zingmark & Rappe, 1977).

        Cutting oils, lubricating oils, and greases can also contain
    diethanolamine, which may react with nitrites and nitrogen oxides in
    the air to form nitrosamines.

        (c) Quenching oils are used for hardening steel. Oxidation and
    cracking of the oil can occur because of the high temperatures
    involved. The amount of benzo (alpha) pyrene in lubricating oils
    increases considerably when they are exposed to heat during use, as in
    motor-car engines, metal quenching, and other processes (Thony et al.,
    1975).  Disposal of waste

        Without a proper method for the disposal of used lubricating and
    other oils, severe environmental contamination and hazards may occur.

        There is a vast literature on methods for the disposal, reuse,
    and recovery of industrial lubricants and much research is being done
    in this field. It would be out of context in this document to go into
    a detailed discussion of the various aspects. For this, the reader is
    referred to Concawe Report 9/73 (Concawe Task Force, 1973) and API
    publication No. 4036 (API, 1969), which contain discussions on the
    situations in Western Europe and the USA, respectively, as well as on
    more general aspects.

        At present, the main ways of disposal are:

    (a)  dumping in sewage systems, waterways, etc; this is illegal in
         many countries and ecologically undesirable;

    (b)  dumping into the ground, in garbage dumps, in dry wells, if
         approved by local authorities;

    (c)  using as road oils, etc;

    (d)  controlled incineration or burning for heat value;

    (e)  re-refining and other recycling methods.

    4.3  Environmental Exposure Levels

        Specific data are not available concerning levels of this group
    of products in air, water, food, or other environmental media, levels
    of possible contamination, and uptake by man.

        Depending on occupation and on the hygiene precautions adopted,
    skin exposure in workers can vary from minimal to very high. No
    systematic measurements have been carried out in this field. Exposure
    to oil mists occurs in certain manufacturing processes and
    applications, such as the operation of automatic lathes. This type of
    exposure has been measured by various authors and will be discussed in
    section Secondary oral intake of unknown quantities of
    mineral oil can take place under these conditions.

        When "sulphofrezol" (approximate composition: 50-60% "goudron"
    (?flux oil), 40-50% spindle oil distillate, and 1.7% sulfur) was used
    as a lubricating and cooling liquid on metal-working lathes, the air
    of the operating premises was found to contain an oily aerosol in
    concentrations of 1-50 mg/m3, hydrocarbons at 26- 150 mg/m3, carbon
    monoxide at 8-12 mg/m3, formaldehyde at 0.05-1.2 mg/m3, sulfur
    dioxide at 2-20 mg/ms, and benzo(alpha)pyrene at 0.01-0.2 mg/m3.
    When multicomponent lubricating-cooling liquids containing chlorine
    and fluorine compounds are used as additives, hydrogen chloride and
    other substances may also find their way into the workroom air. It is
    therefore essential to provide the metal-working lathes with
    vapour-extracting facilities (Medved' et al., 1976).

    4.4  Environmental Distribution and Transformation

        Data on lubricating base oils concerned with distribution among
    media, environmental transformation and degradation, interaction with
    physical, chemical, or biological factors, and bioconcentration are
    not available. However, as mentioned in section 3.4, there is a lot of
    information concerning the microbial degradation of individual
    petroleum hydrocarbons. For example, it has been shown that certain
    polynuclear aromatic hydrocarbons in lubricating oils can be oxidized
    by bacteria; benzo(alpha)pyrene and benzo(alpha)anthracene have been
    shown to be oxidized to cis-dihydrodiols. The oxidation is not thought
    to reach the stage of carcinogenic activation found in mammals, as
    this would result in a trans-configuration (Gibson et al., 1975).

    4.5  Metabolism

        Because of the complex and variable composition of compounds in
    this group, only a few factual data relating to their metabolism can
    be given.

        The skin barrier is permeable only to hydrocarbons of a certain
    relative molecular mass and structure. For paraffinic substances this
    appears to be up to 20 carbon atoms. However, from their studies on
    guineapigs, Hoekstra & Phillips (1963) reported that, because aromatic
    compounds have a more compact structure, compounds in this group with
    a higher number of carbon atoms might still pass through the skin

        In studies on mice, rats, hamsters, rabbits, and dogs, mineral
    oil droplets were phagocytosed in the lungs and clinical observations
    in man have shown that deposition takes place in the hilar nodes, from
    where they may be transported to other organs such as the spleen
    (Sante, 1949; Proudfit et al., 1950; Shoshkes et al., 1950; Wagner et
    al., 1964). Almost all (95-99%) of ingested food-grade mineral oil
    leaves the body unchanged in the faeces, 1-5% being absorbed as such
    via the intestinal mucosa. Phagocytosis may play a part in this. The
    ingested part of the oil is transported throughout the body via the
    lymphatics and the bloodstream. Storage takes place in adipose tissue
    or in the fat in organs. After excessive exposure, mineral oil
    droplets have been identified in mesenteric and portal lymph nodes,
    and also in liver, spleen, and adipose tissue in man (Stryker, 1941;
    Ebert et al., 1966; Boitnott & Margolis, 1966b).

        Data relating to food-grade mineral oil have been reviewed in WHO
    (1974). Very few data are available on the biotransformation and rate
    of elimination of this group of products but data concerning some of
    the components are referred to in section 3.5.

        Injections of 0.5 ml of various mineral oils were made in the
    peritoneal cavity of mice and the oil recovered after 7-24 days (Twort
    et al., 1937). Both the refractive index and density of the oil had
    decreased proportionally, probably as the result of chemical
    transformation in the body. Treatment of mineral oil with sulfuric
    acid and clay, or solvent extraction had a similar effect. The solvent
    extracts, however, showed increased refractive indices and densities.
    The authors suggested that both parameters might be useful indicators
    of the carcinogenicity of the mineral oil.

    4.6  Effects on Experimental Animals

    4.6.1  Short-term exposure

        Data are not available concerning the LD50s of base oils but the
    oral and dermal LD50 data available for commercial lubricating oils
    indicate that, in general, these products are only moderately or
    slightly toxic.

        Acute no-observed-adverse-effect levels have not been determined.
    Oral studies with food-grade mineral oils show that these are
    laxatives. The same applies to non-food-grade commercial mineral oils,
    though it is impossible to predict whether in a certain case a toxic
    or laxative effect will prevail.  Effects of dermal exposure

        More factual information is available on the acute or short-term
    effects of mineral base oils on the skin. In a very thorough study
    Hoekstra & Phillips (1963) examined the effects of mineral oils and
    their fractions on the skin of guineapigs. It appeared that very
    short-chain paraffins had a mainly defatting action on the skin and
    that the effects of longer-chain and aromatic hydrocarbons were
    closely related to the permeability of the skin to these compounds. We
    can do no better than cite the summary of this work:

        "A number of light mineral oils applied topically to the skin of
    guinea-pigs caused a marked epidermal hypertrophy, hyperplasia,
    hyperkeratosis, and subsequent depilation. This dermatoxic effect
    could not be closely related to source of the crude oil or its
    viscosity, degree of refinement, or the acid used in refinement.

        " n-Paraffin, isoparaffin, naphthene and aromatic fractions
    separated from light mineral oil each produced the dermatoxic effect
    as did highly purified individual paraffins from C-12 to C-18. Oleic
    acid caused only a slight dermatoxic effect. Fractional distillation
    of an aromatic-free mineral oil demonstrated that while all
    lower-boiling fractions were dermatoxic, a distillation range was
    reached at which the fractions were innocuous to the skin. This was
    also true for  n-paraffin-, isoparaffin-, monocyclic naphthene-, and
    polycyclic naphthene-rich fractions derived from a mineral oil.
    Fractional distillation of the aromatic hydrocarbons from mineral oil
    representing the same distillation range did not yield fractions
    without skin-damaging effect. Crude estimates of the molecular size of
    the  n-paraffins, isoparaffins, monocyclic naphthenes, and polycyclic
    naphthenes by comparison with the boiling-temperatures of known,
    homologous series of hydrocarbons indicated that the maximum skin
    damage resulted from hydrocarbons of about 14 to 19 carbon atoms. The
    transition point to non-dermatoxic hydrocarbons occurred at about
    21-23 carbon atoms. This was verified with purified  n-paraffins.
    Variations may exist for the different types of hydrocarbons.

        "Simultaneous application of the innocuous "higher-boiling"
    mineral oil fractions with dermatoxic "lower-boiling" fractions or
    with hexadecane greatly reduced or eliminated the skin-damaging
    effects. The alleviation of the skin damage from aromatic fractions by
    simultaneous application of the "higher-boiling", non-aromatic
    fractions was much less pronounced.

        "The hyperkeratotic reaction of the skin to petroleum
    hydrocarbons appears to he a very general response to lipid solvents
    and is not related to any specific reactive group or type of
    structure. Molecular size seems to be very important in determining
    the dermatoxic properties of hydrocarbons, the larger molecules being
    innocuous. Under the conditions of the experiments the very
    low-molecular weight hydrocarbons also had little or no dermatoxic
    properties, presumably because of their volatility. It is postulated
    that the skin barrier is permeable only to hydrocarbons of a certain
    maximal effective size and that penetration into or through the
    barrier is essential for the initiation of the hyperkeratotic
    response. The alleviation of the dermatoxic effect of hydrocarbons by
    admixture with innocuous, higher molecular weight hydrocarbons, is
    likewise explained by a reduction in penetration of the dermatoxic
    component through the Skin barrier" (Hoekstra & Phillips, 1963)

    4.6.2  Long-term exposure

        Most long-term studies with mineral oils have been concerned with
    the carcinogenicity of the compounds. Data concerning mutagenicity,
    embryotoxicity, and teratogenicity are lacking.  Carcinogenic effects

        The carcinogenic activity of certain polynuclear aromatic
    hydrocarbons is attributed to electronic structural features of the
    molecule. The various theories on these mechanisms are discussed in
    detail by Arcos & Argus (1974), Bergel (1974), and Jerina & Daly
    (1974). Carcinogenic polynuclear aromatic hydrocarbons have regions of
    high-electron density in their molecules, the so-called K-regions that
    are readily epoxidized by tissue mixed-function oxidases and more
    specifically by the enzyme aryl hydrocarbon hydroxylase.

        Polynuclear aromatic hydrocarbons are in fact precarcinogens,
    which, though harmless in themselves, are metabolized in the body, by
    the combined action of mixed function oxidase and epoxide hydratase
    (, to biologically reactive intermediates that constitute the
    ultimate carcinogens (Sims et al., 1974). The enzymes responsible are
    active in the liver, and in other organs such as the skin, lungs, and

        Whether, in fact this metabolism leads to detoxication or to
    "lethal synthesis" may differ with various polynuclear aromatic
    hydrocarbons and may depend on many other factors (Anon., 1975). The
    short-lived epoxides resulting from the metabolism of at least some of
    the polynuclear aromatic hydrocarbons are probably the activated
    metabolites with the real carcinogenic effects.

        Evidence is now accumulating that it is the 7,8 dihydroxy-
    benzpyrene - 9,10 oxide of 3,4 benzo(alpha)pyrene that is the
    ultimate carcinogen and, consequently, this has now superseded the
    K-region epoxide in biological importance with regard to
    carcinogenicity (Yang et al., 1976; Thakker et al., 1977; Yagi et al.,
    1977; Koreeda et al., 1978). The enzyme aryl hydrocarbon monooxygenase
    (according to recent international rules of nomenclature) in the case
    of 3,4 benzo(alpha)pyrene, is referred to as benzopyrene
    3-monooxy-genase (EC (de Pierre & Ernster, 1978).

        There are indications that the tissue concentrations of the
    enzyme aryl hydrocarbon hydroxylase vary considerably with the age,
    sex, species, strain, and environment of the animal (Nebert & Gelboin,
    1969). Outside agents, such as polynuclear aromatic hydrocarbons, can
    induce the activity of this enzyme (Wattenberg, 1972). It seems that
    the inducibility depends on genetic factors in both mice and human
    subjects (Nebert et al., 1972; Kellerman et al., 1973). In mice, it
    seems to depend on a single dominant autosomal gene (Nebert et al,
    1972).  Effects of dermal exposure and subcutaneous

        Leitch (1922) repeatedly painted crude shale oil on the skin of
    mice. He obtained skin tumours in a substantial percentage of the
    mice. Similar tests were carried out by Twort & Ing (1928) and Twort &
    Twort (1931) using a range of crude oil as well as more refined
    products of both shale oil and petroleum oil. They found that
    petroleum oils had a lower and sometimes negligible carcinogenic
    activity compared with shale oils. Naphthenic oils were less active
    than oils with a high aromatic content. The more potent fractions
    could be extracted with solvents from the oils.

        Acid treatment of the oils decreased the carcinogenic activity
    and heavier-grade oils were less potent than spindle oils.

        Oils with a boiling-point above 370°C, derived from fluid
    catalytic cracking, appeared to be carcinogenic to the skin of mice.
    The most potent fraction distilled between 430 and 550°C, and the
    carcinogenic activity was contained in the aromatic components of
    these oils.

        Woodhouse (1934) compared the carcinogenicity of sulfur-
    dioxide-solvent-extracts of spindle distillates, derived from
    crude oils from different parts of the world, with that of the
    unrefined spindle oils and coal-tar, using a mouse-skin-painting
    technique. He found that in all cases, the carcinogenic activity,
    which was more or less characterized by its UV-fluorescence spectrum,
    was concentrated in the solvent extract. Potency varied according to

    the source of the crude oil. The potency of the most active extract,
    however, was lower than the activity of coal-tar. By thorough
    sulfur-dioxide-solvent refining, the carcinogenicity of the spindle
    oil was almost completely removed. The same author (Woodhouse, 1950)
    reported studies on the carcinogenic activity of various petroleum
    fractions and extracts. Results were in line with his previous
    findings and with those of other workers. Three white oils including
    medicinal liquid paraffin gave negative results.

        More recent studies have been aimed at identifying the
    carcinogenic substances.

        Dilution of carcinogenic oils with non-carcinogenic oils more
    than proportionally reduced the carcinogenic activity, which at times
    disappeared completely. Mild hydrogenation or treatment with active
    absorbents reduced, but did not abolish carcinogenicity. Mild acid
    treatment, on the other hand, did not have such an effect (Smith et
    al., 1951). Eight samples of unrefined "slack waxes" obtained from
    pressing operations -- still containing 12-29% of oil -- were painted
    3 times a week on the skin of white mice (Smith et al., 1951).
    Aromatic extracts, obtained by the solvent refining of these waxes,
    were examined in the same way. After skin-painting for almost the life
    span of the animals, some benign rumours were found with all samples
    and in a few cases, skin carcinomas developed. The aromatic extracts,
    however, were much more active. The authors concluded that the
    aromatic components which were removed by further refining of the
    waxes, were the cause of the carcinogenic activity of "slack waxes".

        Fischer et al. (1951) described methods for the determination of
    polynuclear aromatic hydrocarbons: the ultraviolet absorption method,
    the caffein extraction method, the chromatographic ref-ractometric
    method, and the maleic anhydride method. Levels, determined by any of
    these methods, were fairly well correlated with the tumorigenic
    potency of these oils as established in animal experiments. These
    analytical techniques are relatively simple and much more rapid than
    long-term animal experiments. They are considered to have some
    predictive value. A further development is the DMSO
    extraction/refractive index method.

        The correlation between the analytical data and the carcinogenic
    activity in skin-painting studies on mice is now under investigation
    (Shell Toxicology Laboratory -- private communication) and encouraging
    results have been obtained with the lower- and higher- range
    polynuclear hydrocarbons. The compounds in the middle range are still
    under investigation.

        Auld (1940) considered that it was not the general
    UV-fluorescence that was characteristic of carcinogenicity but the
    pattern of the spectrum and its classification. However, in a report
    by the Analytical Subcommittee of the Institute of Petroleum
    (Catchpole et al., 1971a), it was concluded that, at the time of the
    report, there was no suitable, easy and quick method for determining
    either the total polynuclear aromatic hydrocarbons or individual
    carcinogens in them.

        The tumorigenic activity of various concentrations of a large
    number of pure aromatic hydrocarbons was examined in different strains
    and species of animals by Hartwell (1951), who found that the potent
    substances contained 4,5, or 6 condensed aromatic rings with
    relative-molecular masses ranging from 230 to 320.

        Cook et al. (1958) tried to isolate individual carcinogens from 3
    Kuwait crude oils by fractional distillation and various treatment
    processes. They tested the fractions obtained on the skin of mice and
    rabbits and found that more of the carcinogenic activity was contained
    in the fraction distilling between 350 and 400°C and that this
    activity was associated with the aromatic constituents. Solvent
    extraction with aqueous acetone or furfural removed the activity,
    which passed into the extract (20% of the original fraction). Several
    polynuclear aromatic hydrocarbons such as di-, tri-, and tetramethyl-
    phenanthrenes, tetramethylfluorene, 1-methylpyrene, 1,2-benzofluorene
    and 8-methyl-1,2-benzofluorene could be identified in these extracts
    as well as some complex organic sulfur compounds such as
    dibenzothiophen derivatives and polycyclic thiophens, a number of
    which are known to have carcinogenic activity. Pentamethyl-carbazole
    was identified as an example of a complex organic nitrogen compound.
    Similar findings were obtained by Bogovsky et al. (1960) on
    fractionating Estonian shale oil.

        Approximately 100 fractions were separated from a catalytically
    cracked oil by various techniques (Tye et al., 1966). Selected
    fractions were chemically analysed and assayed for carcinogenicity by
    repeated application to the skin of C3H mice. In the highest-boiling
    fractions (438-455°C), the major carcinogens were 4 and 5 ringed
    polynuclear aromatic hydrocarbons, benzo(alpha)pyrene as a
    characteristic carcinogen was present at a concentration of 0.4%. In
    the intermediate boiling range (404-438°C), unsubstituted and
    methyl-substituted 4-ringed polynuclear aromatic hydrocarbons formed
    the major carcinogens, benz (a)anthracene and its alkyl homologues
    being present at a concentration of 0.4%. In the low-boiling fraction
    (339-404°C), assorted smaller molecules including alkyl-3-ringed
    polynuclear aromatic hydrocarbons were present.
    Benzo (c)phenanthrenes, the most dominant carcinogens in this
    fraction, were present at a concentration of 0.01%. The carcinogenic
    potency in the bioassay was found in the intermediate- and
    high-boiling fraction (boiling-range 404-455°C); fractions boiling at
    under 349°C did not appear to be carcinogenic.

        Generally, where the alkyl-substituted 4-6 condensed-ring
    polynuclear aromatic hydrocarbons were concerned, the longer the
    side-chain, the lower the carcinogenic activity (Auld, 1950).

        These findings were confirmed by the United Kingdom Medical
    Research Council (1968), who reported similar studies. Uncracked crude
    oil fractions boiling at above 350°C, which had the highest
    carcinogenic activity in skin tests on mice and rabbits, contained the
    same or similar polynuclear aromatic hydrocarbons; no other new
    carcinogens were found. After solvent extraction, the carcinogenic
    activity of the extract was much higher than that of the raffinate,
    which was very low.

        The carcinogenicity of individual polynuclear aromatic
    hydrocarbons will not be discussed in this document. For this, the
    reader should refer to IARC (1973).

        The fact that various cracking processes considerably increase
    the contents of polynuclear aromatic hydrocarbons in mineral oils has
    been demonstrated by Kennaway (1925), Twort & Fulton (1930), Twort &
    Twort (1935), Pates (1952), and Dietz et al. (1952). Kennaway (1925)
    discovered that skin cancer of mice could be produced with synthetic
    tars obtained by pyrolising substances like acetylene, isoprene,
    yeast, human skin, and a non-carcinogenic petroleum. Badger (1962)
    pyrolysed a whole range of aliphatic and simple aromatic hydrocarbons
    at 700°C. It was concluded from an analysis of the resulting tars
    that, at high temperatures, polycyclic aromatic hydrocarbons were
    formed from simpler hydrocarbons via primary radicals formed by
    carbon-hydrogen and carbon-carbon fission. The same process occurred
    at 550°C, but to a much lesser extent.

        Skin tests on C3H-mice using 15 base oils with known content of
    polynuclear aromatic hydrocarbons, which, in some cases, only differed
    in theft refining history, revealed that solvent-refining removed the
    carcinogenic components to such an extent that none of the oils
    treated in this manner induced carcinomas (Bingham et al., 1965).
    Solvent extraction was carried out with the usual solvents including
    phenol, cresol, and furfural. Conventional acid and clay treatment
    only removed certain of the polynuclear aromatic hydrocarbons and all
    oils treated in this way still retained some carcinogenic activity. In
    these tests, a general correlation was again found between the content
    of 4 and 5 ring polynuclear aromatic hydrocarbons and the
    carcinogenicity of the base oils examined.

        Catchpole et al. (1971b) compared mass spectrometry analysis of
    an untreated distillate with its solvent-treated and its hydrogenated
    derivatives. The decrease in polynuclear aromatic hydrocarbons
    thiophenes, and sulfur in both treated samples compared with the
    untreated sample was quite marked. Smaller differences were found
    between the levels in the two refined samples.

        In studies by Boehme & Huehnermann (1966), the relative amounts
    of aromatic compounds present in some of the more purified mineral oil
    products were determined from their UV absorption spectra. The
    relative concentrations were:

                   medicinal white oil               1
                   paraffin waxes                  100
                   micro crystalline waxes         300
                   white petrolatum               1000
                   yellow petrolatum            10 000

        The carcinogenicity of a sample of amber petrolatum was tested on
    the skin of mice. A 15% solution of the petrolatum in iso-octane, did
    not show any significant carcinogenicity. The solvent-extracted
    aromatic fraction (1.2% of the original material) tested in iso-octane
    solution at 50 times its concentration in the petrolatum did not
    produce any carcinogenic effects on mouse skin (Lijinski et al.,
    1966). Studies are reported by Oser et al. (1965) in which 3 kinds of
    pharmaceutical and food-grade petrolatum were administered to mice in
    the form of a single subcutaneous injection of 100 mg of petrolatum
    per mouse. Observations over 18 months did not reveal any carcinogenic
    or other toxic effects.

        Liquid paraffin was found to be non-carcinogenic in long-term skin
    testing on mice by Twort & Twort (1931) and Woodhouse (1934). White
    mineral oil was also found to be non-carcinogenic in mice after
    long-term skin application (WHO, 1974).

        Shubik et al. (1962) examined 36 samples of petroleum wax. Eight
    samples contained identifiable polynuclear aromatic hydrocarbons; the
    highest concentration was 0.64 mg/kg. The results of skin and
    subcutaneous testing follow in the author's words:

        "Five petroleum waxes were tested by repeated skin application in
    benzene solution to mice and rabbits. In addition one of the test
    waxes was fractionated and its aromatic and non-aromatic components
    were tested separately on mice, also by repeated skin applications.
    Solvent-treated controls were kept. No carcinogenic effects were
    detected. Five petroleum waxes were tested in mice by subcutaneous
    implantation in disc form. Fibrosarcomas developed around the implants
    with incidences correlated to the melting points of the waxes. In
    addition, one of the test waxes was fractionated and its aromatic and
    non-aromatic components tested separately; the same wax was also
    tested subcutaneously in powdered form. The findings indicate that the
    subcutaneous sarcomas occurred as a result of the physical rather than
    the chemical properties of the materials."

        From the various studies, it would seen that there is no relation
    between the carcinogenicity of a lubricating base oil and its
    potential to cause dermatitis.

        In all the previously mentioned studies and others by Horton et
    al. (1963) and Bingham & Horton (1966), there is general agreement
    that the carcinogenicity of a mineral oil is largely related to the
    aromatic fraction with a boiling-point above 370°C, and more
    particularly to the polynuclear aromatic hydrocarbons containing 4-6
    condensed benzene rings. However, some long-chain, aliphatic,
    alicyclic, and alkyl-aromatic hydrocarbons from a lower boiling-range
    with 10-20 carbon atoms, such as  n-dodecane, cyclohexyl-decane, and
    dodecyl-benzene may act as accelerators or co-carcinogens. Though
    completely non-carcinogenic themselves, they were found to increase
    tumour incidence and reduce the time of appearance, when carcinogenic
    fractions dissolved in them were applied, to the skin of mice (Horton
    et al., 1963; Bingham & Horton, 1966). However, in order to act as a
    cocarcinogen,  n-dodecane must be present in a concentration of
    20-30% or more. Such solutions in accelerating solvents show an
    unusual capacity to spread upon the skin (Horton et al., 1957, 1965).

        In a further study on the effects of co-carcinogenic compounds on
    the carcinogenic action of benzo(alpha)pyrene and benz (a)anthracene
    on the skin of mice (Bingham & Falk, 1969), the co-carcinogenicity of
     n-dodecane was confirmed. However, when the authors claim "that
    there is a 1000-fold increase in the enhancement of potency of low
    concentrations of benzo(alpha)pyrene and benz (a)anthracene when
    dodecane is the diluent", this statement may not be fully justified by
    the results obtained in relatively small numbers of animals per test
    group. Nevertheless 50%  n-dodecane in the solvent decaline doubled
    or trebled the tumour incidence in the highest dose-group, and tumours
    were found at much higher dilutions than when decaline alone was used
    as a solvent. When 2-dodecanol and 2-phenyldodecane were used in
    various concentrations in the solvent of benzo(alpha)pyrene, higher
    concentrations of these 2 substances shortened the interval of
    appearance of tumours rather than increasing the total incidence of

        From this it would appear that these accelerators would not have
    any effect, when present in an intrinsically non-carcinogenic oil, and
    that they would only have an effect in other oils, when present in
    appreciable concentrations. This effect seems to be due, at least in
    part, to the spreading power of the solvent causing more intimate
    contact with a greater skin area. On the other hand, a more plausible
    explanation could be an increase in P-450 enzyme induced by dodecane,
    which possibly does not occur with 2-dodecanol and 2-phenyldodecane.
    3,4 Benzo(alpha)pyrene can induce P-450 microsomal mixed function
    oxidase and this can also catalyse arylhydrocarbon (AH) monooxygenase
    activity (de Pierre & Ernster, 1978). The increase in P-450 induced by
    dodecane will accelerate and increase the formation of the ultimate
    carcinogen 3,4 benzo(alpha)pyrene and thus increase the total
    incidence of tumours. However, these substances will not normally be
    present in base oils and related products, because they fall into a
    different boiling range.

        Apart from this, some frequently used additives - which in
    themselves are non-carcinogenic - such as elemental sulfur and some
    sulfur-containing compounds such as benzyldisulfide, ditertiary
    butylpolysulfide and ditertiary octylpolysulfide (Horton et al., 1965;
    Bingham et al., 1965; Bingham & Horton 1966) as well as certain
    phenols (Boutwell & Bosch 1959) have also been shown to enhance the
    carcinogenic activity of polynuclear aromatic hydrocarbons on the
    mouse skin. Addition of sulfur to a non-carcinogenic oil did not, of
    course, have any effect on the carcinogenicity (Bingham et al., 1965).
    Baldwin et al. (1964) reported that additives such as lead naphthenate
    did not have an enhancing effect and there are indications that other
    components of complex mineral oils with a boiling-range above 370°C
    act as inhibitors of the carcinogenic effect of polynuclear aromatic
    hydrocarbons, e.g., the saturated (probably cyclic) hydrocarbons
    (Bingham & Horton, 1966).

        Sunderland et al. (1951) reported skin tests of mineral oil
    fractions on mice, under various conditions. They found that washing
    the skin with soap and water, after the application of the oil,
    reduced both the number of tumours and the rate of appearance. The
    reduction was related to the length of the interval between oil
    application and washing. Painting once, instead of twice, weekly
    greatly reduced the rate of tumour appearance.

        From human experience (section, it is known that the
    ultraviolet radiation of sunshine has a potentiating effect on the
    carcinogenicity of mineral oils. Similar indications exist from animal
    studies (Emmett, 1975). It has also been demonstrated that certain
    co-carcinogenic  n-alkanes may increase the carcinogenic potential of
    certain wavelengths of UV light on mouse skin (Bingham & Word, 1977).

        In comparative studies with various mineral oil fractions on the
    skin of mice and rabbits, it became apparent that the rabbit skin was
    more sensitive than the mouse skin according to the type, number, and
    growth rate of tumours (Cruickshank & Squire 1950; Hieger & Woodhouse
    1952; Antonov & Lints 1960; UK Medical Research Council, 1968). In
    some instances, mineral oil fractions were non-carcinogenic to mouse
    skin, but positive on the skin of rabbits (Shubik & Saffiotti), 1954).
    While, rats and guineapigs are apparently less sensitive than mice
    (Sugiura et al., 1949; Desoille et al., 1973) Rhesus monkeys appear to
    be fairly sensitive (Sugiura et al., 1949).

        As to the suspected causes of intra- and inter- species
    differences in susceptibility to polynuclear aromatic hydrocarbons,
    the levels of the enzymes forming and detoxifying the biological
    reactive intermediates, the ultimate carcinogens, in the tissue of the
    various strains and species might be one of the important factors
    (section Clear intra-species differences in tumorigenic
    response have been reported by, for example, Smith & Sunderland (1951)
    and Gilman & Vesselinovitch (1955).

        In addition to these studies on "pure" mineral oil fractions and
    various additives, some studies with metal working oils and textile
    oils have been published.

        Two cutting oils based on sulfurized mineral oils, were diluted
    with water and were tested in various concentrations on the skin of 3
    strains of mice. Both were found to be carcinogenic. A marked
    reduction in incidence and an increase in induction time of tumours
    was found at a dilution of 1:8 compared with 1:4 (Gilman &
    Vesselinovitch, 1955). The same authors (Gilman & Vesselinovitch,
    1956) compared a straight cutting oil and a water-soluble cutting
    fluid in 2 different strains of mice. They found a consistent,
    comparable but low incidence of skin tumours in 3 separate trials.

        In a later study, 3 commercial additive-containing cutting oils,
    one of which was an emulsifiable oil, were repeatedly applied to mouse
    skin for up to 31 weeks. Carcinogenic skin changes were observed with
    all these oils but were, possibly, less marked with the emulsifiable
    oil. In addition to these carcinogenic effects, focal necrosis of the
    liver associated with amyloid deposition and amyloidosis of the skin,
    spleen, and kidneys were observed. The additives may have had a
    contributory effect in some of the pathological changes observed
    (Jepson et al., 1977).

        In the case of cutting oils, the temperatures to which the oils
    are exposed at the cutting edges of the tools are such that cracking
    of the oil might conceivably occur and theoretically a
    non-carcinogenic cutting oil might become carcinogenic during use. An
    unspecified cutting oil from the sump of a machine was tested on the
    skin of mice and rabbits. It induced benign tumours in rabbits only
    (Cruickshank & Squire, 1950). As the fresh oil was not examined, no
    conclusion can be drawn concerning the previously-mentioned

        Unused cutting oil, used cutting oil, and residue from the sump
    were compared in skin tests on 2 strains of mice by Dargent et al.
    (1967). Both used and unused cutting oil caused a high incidence of
    skin ulceration. Hyperkeratosis and papillomas were more frequent in
    the case of used oils and a single case of skin cancer occurred in the
    groups of mice treated with used oil and sump residue.

        Cutting and quenching oils, fresh and used, were tested on the
    skin of rats, guineapigs, and mice. All tests on rats and guineapigs
    were negative. In mice, skin tumours were more numerous and more
    malignant with used oils than with fresh oil. Only used oils produced
    tumours in organs distant from the site of application. The unused
    quenching oil was found to contain a benzo(alpha)pyrene level of
    0.6-0.8 mg/kg (ppm); in the used oil, this fraction had increased to
    20 mg/kg, which is in agreement with the finding of its increased

    carcinogenicity. The increase in carcinogenic poly-nuclear aromatic
    hydrocarbons may be the result of thermal cracking due to the heat of
    the process (Desoille et al., 1973). The studies of Thony et al.
    (1975) indicated that the increase in poly-nuclear aromatic
    hydrocarbons in cutting oils was very small and considerably less than
    for quenching oils and engine oils. The benzo(alpha)pyrene content of
    new cutting oils ranged from 0 to 150 mg/kg, compared with 0 to
    250 mg/kg for used cutting oils.

        A sample of commercial jute batching oil of unspecified origin and
    composition, containing a concentration of 3,4-benzopyrene of less
    than 1 mg/kg, was tested for carcinogenic activity on the skin of
    mice. The oil in question induced malignant skin tumours in 6 out of
    24 test animals and proved to be a potent tumour promotor in mice
    pre-treated with 7,12-dimethylbenz (a)anthracene (DMBA) (Roe et al.,

        To summarize, it may be concluded that:  (a) the carcinogenic
    activity of mineral oils seems to be related mainly to the presence
    and concentration of certain polynuclear aromatic hydrocarbons,
    containing 4,5, or 6 condensed rings; and  (b) cracking processes
    tend to increase the polynuclear aromatic hydrocarbon contents in
    petroleum products. For example such compounds may accumulate in a
    metal working oil in contact with the host cutting edge of a tool.

        The polynuclear aromatic hydrocarbon content of mineral oils can
    be decreased by solvent extraction and/or by hydrogenation. Acid
    treatment is less effective for this purpose.

        Analytical methods for the determination of total polynuclear
    aromatic hydrocarbons should provide a useful, quick, and cheap tool
    for predictive screening of mineral oils for carcinogenicity. These
    methods should be biologically validated. The correlation will not
    always be good, because the carcinogenicity of polynuclear aromatic
    hydrocarbons varies considerably and because of the unpredictable
    effects of cocarcinogens, inhibitors, and accelerators.

        Various substances that are used as additives such as sulfur
    compounds, as well as substances that may normally be present in
    mineral oils, such as  n-dodecane, may act as cocarcinogens. Other
    saturated hydrocarbons, normally present, may act as inhibitors of the
    same effect.

        It is clear from animal studies that washing with soap and water
    substantially reduces the hazard to the skin of repeated and long
    contact with potentially carcinogenic oils.  Effects of inhalation and intratracheal exposures

        The aspiration hazard and toxicity for animals of a number of
    hydrocarbons and hydrocarbon mixtures was determined by Gerarde
    (1963). This study has been discussed in more detail in section 3.6.1.
    He found that the aspiration hazard decreased with increased viscosity
    of the product and with mixtures containing low viscosity products.

        Mice were exposed to mists of various mineral and vegetable oils
    with an average droplet size of 2.5 µm, 80% of the particles retained
    in all areas of the lungs were 2.5 µm or less in diameter. The highest
    concentration of retained particles was found around the terminal
    bronchioles and alveolar ducts in all parts of both lungs. Oil
    particles were immediately phagocytosed, a process that was
    essentially completed within 48 h, unless prolonged exposures (2-4
    weeks) had been given. The initial concentration of retained oil
    droplets was similar for all types of oil mists. During a 90-h
    follow-up, however, the concentration of vegetable oil droplets
    decreased progressively, whereas the concentration of mineral oil
    droplets remained practically unchanged. After 2-4 weeks of exposure,
    mineral oil droplet retention gave rise to localized slight
    foreign-body reactions as well as to a few patches of lipoid
    pneumonia. Of the other oils, only cod liver oil caused a moderate
    foreign-body reaction (Shoshkes et al., 1950).

        The effects of prolonged inhalation of oil mists (mineral oil
    levels in air of 63-132 mg/m3) were observed in mice, rats, rabbits,
    and monkeys. Ordinary automobile lubricating oil and a smoke-screening
    oil, were tested for periods varying from 100 to 365 consecutive days
    (Lushbaugh et al., 1950) The authors found that surprisingly little
    oil accumulated in the lungs and that whatever was retained was
    rapidly phagocytosed and transferred to the pulmonary connective
    tissue and the hilar lymph nodes. Lipoid pneumonia was not found to be
    a hazard at these dosages, though the incidence of infectious
    pneumonia in the exposed monkeys greatly increased. Many exposed
    monkeys died of a hyperplastic gastritis, probably because much of the
    inhaled oil was initially deposited in the nasal passages and
    subsequently swallowed. Hyper-plastic gastritis was especially evident
    with the shale oil (which is different from petroleum oil) used as
    smoke screening oil (Lushbaugh, 1947). No significant increase in
    tumour incidence or reduction in the latent period of tumour
    production was found in the mouse study.

        Hueper & Payne (1960) compared the carcinogenicity of various
    petroleum products and coal-tar in long-term tests on mice, rats, and
    guineapigs. Rats and guineapigs were exposed for 6 h/day, 4 days a
    week, for up to 2 years, to a cutting oil mist consisting of a 10:1
    mixture of neutral paraffin and prime lard oil. In some cases, this
    caused multi-focal adenomatosis in the lungs of the animals. A
    carcinoma of the lung was found in only 1 of 105 exposed rats and not
    in any of 65 guineapigs.

        In tests on mice, Wagner et al. (1961) found that inhalation of
    either mineral or motor oil mist reduced the acute lethal effects of
    respired oxidants such as ozone and nitrogen dioxide. The effect was
    demonstrable only after a latent period of up to 8-9 days following
    oil mist exposure and was thought to result from the formation of a
    thin film of oil on the alveolar surfaces.

        Long-term inhalation toxicity studies using a highly purified
    white mineral oil, composed of naphthene-based saturated hydrocarbons,
    were reported by Wagner et al. (1964). Five species of laboratory
    animals (dog, rabbit, rat, hamster, mouse) were exposed daily, for
    periods from one year to 26 months, to a petroleum-base mineral oil
    mist at concentrations of 5 mg/m3, the current USA threshold limit
    value, and 100 mg/m3. Histological evaluation of tissues of the dogs
    and rats exposed to 100 mg/m3 showed significant pulmonary alveolar
    and hilar lymph node oil deposition and/or lipid granuloma formation
    after 12 months of exposure. In addition, these animals showed
    significant increases in the activities of basic and
    magnesium-activated phosphatases.

        Body-weight gain, haematological variables, and respiratory
    function values did not deviate significantly from the control data at
    any of the exposure levels. Studies with a spontaneous
    pulmonary-tumour-susceptible strain of mouse presented equivocal
    evidence of an increased rate of tumour formation at the 100 mg/m3
    concentration. These findings suggest that prolonged exposure to a
    mineral oil mist concentration of 5 mg/m3 would not present any toxic
    hazard. It would appear, however, that protracted exposure at
    approximately 100 mg/m3 would, in time, produce harmful physiological

        The toxicity of aerosols of various petroleum oils (industrial,
    transformer, and compressor distillates) differed only slightly in a
    long-term experiment by Lutov (1974). White rats were exposed to
    concentrations of 13, 30, and 60 mg/m3 for 5 h/day, for 6 months.
    Changes in the electrocardiogram, and reductions in arterial pressure,
    respiratory frequency, and immunological reactivity were seen even at
    12-13 mg/m3, which was considered to be just above the threshold
    level. A concentration of 5 mg/m3 is recommended as a maximum
    permissible concentration for petroleum oil aerosols without

        In a further long-term study on white rats, Lutov et al. (1976)
    studied the toxicity of petroleum oil aerosols in concentrations
    ranging from 11.4 ± 1.5 to 61.4 ± 5.2 mg/m3 in combination with
    products obtained by thermo-decomposition, i.e., hydrocarbons in
    concentrations ranging from 200.0 ± 5.8 to 410.0 ± 12.8 mg/m3 and
    carbon monoxide in concentrations ranging from 11.2 ± 1.5 to
    35.4 ± 4.6 mg/m3. White female rats were exposed for, 5 h/day over a
    6-month period. The combined exposure was found to produce more marked
    effects on the parameters tested in the earlier experiment.

        The minimum concentrations of oil aerosol that caused functional
    changes in the respiratory system with a single inhalation were in the
    range of 860-1200 mg/m3. When concentrations of 53 and 60 mg/m3 were
    used in the long-term experiment, physical growth was impaired and the
    functional condition of the nervous system and the liver changed.
    There were morphological changes in the lungs including a
    catarrhal-desquamative bronchitis, a swelling of the alveolar
    membranes, formation of oleogranules, and the presence of a large
    quantity of oleophages and oil droplets in the lymphatic vessels and
    the peribronchial and bronchopulmonary lymphatic nodules. At
    concentrations of 10-17 mg/m3, the changes were slight and
    reversible. A maximum admissible concentration in the air of a work
    place of 5 mg/m3 is the official USSR exposure limit (Ivanov et al.,

        In tests on rabbits, Laughlen (1925) demonstrated that mineral oil
    given by mouth or nose can enter the trachea. Corper & Freed (1922),
    injected olive oil and medicinal mineral oil intratracheally into
    rabbits in amounts of 0.5-1.0 ml. The oil was readily aspirated into
    the finest pulmonary divisions and into the alveoli. It was retained
    for months and caused a mild proliferative reaction typical of a
    foreign body reaction. In studies by Pinkerton (1928), rabbits and
    puppies were injected intratracheally with animal, vegetable, and
    medicinal oil. Complete removal of the oil from the lungs took several
    months in all cases. Neutral vegetable oil produced practically no
    reaction, animal oils caused giant cell formation and rapid and marked
    pulmonary fibrosis. Mineral oil was rapidly phagocytosed, giant cell
    formation and slight fibrosis were apparent after 2-3 months, and
    storage of the oil took place in the bronchial lymph nodes.  Dietary studies

        Long-term oral studies have not been conducted with lubricating
    base oils.

        Lushbaugh & Hackett (1948/1949) carried out a study in which rats
    received an average of 0.2 ml/rat per day of a highly refined
    diesel-engine lubricating oil, used as smoke screening oil, in theft
    diet for a period of 14 months. In this group of 40 rats, 2 developed
    foci of colonic mucosal hyperplasia and one developed colonic

        Results of various dietary studies using food-grade and
    pharma-ceutical-grade materials, such as medicinal and food-grade
    mineral oil, and food-grade paraffin waxes are included in the
    following summary, though these studies with highly purified material
    are not representative for the less purified grades.

        Schmahl & Reiter (1933) fed 2% (w/v) mineral oil in the diet of
    rats for 500 days without adverse effects. In studies by Daniel et al.
    (1953), rats were kept for 15 months on diets supplemented with 10%
    liquid paraffin, without adverse effects. Five kinds of petroleum
    waxes were tested by feeding rats a diet containing 10% of the wax for
    2 years. The rats were then observed until natural death. No toxic or
    carcinogenic effects were found (Shubik et al., 1962). In the studies
    by Oser et al. (1965), already reported in section, 3 kinds of
    petrolatum were also administered to rats in the diet at 50 mg/kg
    diet. Observations over 2 years did not reveal any carcinogenic or
    other toxic effects.

    4.7   Effects on Man

        The general population does not have any contact with base oils;
    contact with the commercial products derived from them will, at most,
    be occasional and of a lower order of magnitude than occupational
    exposure. Cases of accidental ingestion are exceptions.

        However, pharmaceutical grade liquid paraffin in the form of
    medicinal oil is widely used as a laxative (faecal softener).

        Occupational exposure to base oils is restricted to the small
    group of workers who manufacture them in oil refineries and to workers
    in blending units, who mix and blend them with additives in order to
    produce commercial products such as lubricating oils, greases,
    metal-working oils, and textile oils. These activities are normally
    carried out in closed systems in which case occupational contact is
    minimal and discontinuous, usually accidental. This also applies, when
    the finished product is put into containers.

    4.7.1  Occupational exposure

        Epidemiological and clinical data concerning base oils are almost
    non-existent. Thus, in this section, it is only possible to analyse
    epidemiological studies of workers exposed to products containing base
    oils, such as lubricating oils, metal-working oils, and textile oils.

        From the list of lubricating oil products given in section 4.2.2,
    it is clear that various groups of workers are occupationally exposed
    to these products, the most widely-used being the metal-working oils
    and textile oils.

        The magnitude of occupational exposure varies considerably. In the
    case of some lubricants and transformer oils, handling is only
    occasional, and, even then, exposure is minimal. In other situations,
    such as in the earlier years of mule spinning and in work with
    automatic lathes of old design, extremely high exposure did - and
    sometimes still does occur. Not only is there continuous direct
    contamination of clothes and exposed parts of the skin, but the rapid
    movement of the machinery may turn the oil into an aerosol and thus
    generate an oil mist that can be inhaled and further contaminate skin
    and clothing. Equipment and floors may become covered with an oil-film
    and situations have been described where oil even dripped from the

        A certain degree of oil mist generation may also occur in the
    printing and rubber industries and with pneumatic equipment (e.g.,
    drills), especially under conditions of limited ventilation such as
    are found underground.

        Even under the best technical conditions, it may sometimes be
    difficult to completely avoid contamination. For example, in the case
    of toolsetters, the wearing of protective clothing impedes easy
    movement, and clothing, including underwear, may become soaked with

        Henry (1946/1947) gave an excellent insight into the types and
    magnitude of occupational exposure up to the time of the report. It is
    known that some of these conditions had continued for a period of
    about 20 years. However, in many countries, great improvements have
    been made since then. An understanding of the range of such exposures
    is needed to put epidemiological studies of later years into
    perspective, especially in view of the long latency of carcinogenic
    effects. In the evaluation of such studies, it has to be kept in mind
    that today's findings may reflect the industrial hygiene situation of
    20-30 years ago.  Skin disorders

        A great variety of skin disorders attributed to working with
    mineral oil or with products based on mineral oils, such as metal
    working fluids, are mentioned in the medical literature. This is not
    surprising considering the many factors that influence theft
    development (van Raalte, 1963; Key et al., 1966; Kipling, 1968;
    Hodgson, 1970, 1973).

        The main factors include:  (a) the degree of intrinsic potential
    of a mineral oil product to damage the skin;  (b) the integrity of
    the skin;  (c) the degree and continuity of contact between oil and
    skin; and  (d) individual predisposition.

        The situation, however, is more complex than this, for, in actual
    practice, a multitude of other factors may influence the main
    conditions to such an extent and in such a complex way, that a
    cause-and-effect relationship may become obscured. Most authors agree
    that practically all skin disorders attributed to exposure to mineral
    oil products can be prevented entirely by adequate industrial and
    personal hygiene practices, and that the majority of cases have
    occurred in workshops where inadequate conditions prevailed.

        Some of the more important factors in the complex interplay are:

    (a) Factors related to the mineral oil product used:

        (i)     Base oil:

                the lower the boiling-point of the oil, the more
                pronounced the solvent action of the product; this causes
                defatting of the skin and leads to dryness, chapping,
                scaling, and cracking;

                the higher the boiling-point, the more blocking of skin
                pores occurs, giving rise to acne formation;

                some mineral oils are more irritant than others; the
                lower-boiling fractions are sometimes, but not always,
                more irritant than higher-boiling fractions (section

                mineral oils themselves do not appear to be sensitizers.

        (ii)    Additives:

                these may be primary irritants or sensitizers in theft own
                right (e.g., chromium salts), though manufacturers try to
                avoid the use of such additives;

                solvents and detergents increase the defatting effect of
                the lower boiling-range oils;

                some chlorinated additives, such as chlorinated
                naphthalenes, may cause chloracne. The use of chlorinated
                naphthalenes was discontinued in most countries, many
                years ago.

        (iii)   Changes in the composition of the oil that may occur
                during its use:

                cracking of oil fractions may occur due to heat;

                reactions may occur between components of the mixture or
                between them and materials that are added at a later

                metal salts or ions may be formed in the mixture or
                solution in the case of metal-working oils; in the case
                of, for example, chromium and nickel, this can cause skin
                reactions in sensitized workers.

        (iv)    Impurities of all kinds may accumulate in, for instance,
                metal-working oil baths in which the oil is not regularly
                changed. Important among these impurities are: metal
                particles, which may cause microtraumata of the skin; and
                microorganisms, which may cause inflammation of the skin
                by way of infection or exotoxins; bacteria, yeasts, or
                fungi may be present in mono- or mixed culture, and some
                of these organisms can degrade an oil and form potentially
                irritating compounds.

    (b) Factors related to the work situation:

        (i)     design of workshop and equipment determine to a large
                extent the magnitude and duration of exposure to the oil,
                and whether this exposure is continuous or intermittent;

        (ii)    availability of general and exhaust ventilation of
                sufficient design and capacity may determine whether there
                is exposure to oil mist or not;

        (iii)   use of protective clothing such as gloves, will diminish
                duration and intensity of skin contact;

        (iv)    general hygienic facilities such as wash basins near the
                work-place, shower facilities, frequent changing and
                laundering of work clothing, all of which help in limiting
                the extent and duration of exposure;

        (v)     hands and contaminated parts of the body should be washed
                with fatty toilet soap and, after washing the skin should
                be treated with a suitable emollient cream; use of
                solvents, and alkaline or abrasive soaps for washing can
                damage the skin and contribute to the occurrence of skin

    (c) Individual factors:

        (i)     general and hereditary conditions of the skin may
                predispose to adverse skin effects from all sorts of

        (ii)    work discipline and safety-mindedness can influence the
                duration and intensity of the exposure;

        (iii)   proper use of safety equipment and general hygiene
                facilities, as well as personal hygiene in the form of
                frequent bathing and changing of underwear, will help to
                avoid over- and prolonged exposure.

        Contamination of the skin may often occur despite all precautions
    taken, particularly in the case of metal-working oils. Wiping with
    oil-soaked rags is an additional source of contamination and may cause
    skin lesions. Continuous wearing of oil-contaminated clothing is an
    important factor in the etiology of scrotal cancer. Rapidly rotating
    machinery may generate oil foams and mists.

        The most common form of skin disorder is acute or chronic contact
    irritative (toxic) dermatitis caused by the irritative action of
    various components, additives, and/or impurities in mineral oils.
    Dermatitis may be preceded by defatting and/or maceration of the skin.
    Mechanical irritation, microtraumata, and skin cuts may play a role in
    its origin. Clinical signs of contact irritative dermatitis are, in
    order of severity, erythema, oedema, bullae or necrosis, and sharp
    demarcation of the affected areas from unaffected ones.

        The other type of dermatitis is contact allergic dermatitis
    (synonym: contact eczema) caused by allergic sensitization to various
    allergens. Additives or impurities are the most allergenic components
    of oil formulations. The signs of eczema are more variable then those
    of toxic dermatitis and include erythema, papulae, vesiculae, bullae,
    scales, hyperkeratoses, and rhagades. These lesions have a tendency to
    spread into areas that have not been in direct contact with the
    allergen. Eczema may be preceded by contact irritative dermatitis,
    from which it develops by secondary sensitization.

        Oil folliculitis, or oil acne is characterized by the triad
    comedones, folliculitis, and follicular scars. The lesions are found
    on the parts of the body with the greatest exposure. Friction from
    clothing and machinery rubbing the oil into the exposed parts of the
    skin, is an important additional factor. First there is plugging of
    the hair follicles and pores of the skin by follicular hyperkeratosis,

    cell debris, and oil with its impurities, followed by blackheads and
    secondary infection. Poor personal hygiene is the main cause. Oil acne
    occurs more often in the earlier years of exposure to oil. Later,
    there appears to be a gradual change in the reaction of the skin to
    the oil (Kinnear et al., 1954). Chlorinated naphthalenes and related
    compounds have given rise to chloracne.

        Photosensitivity is an abnormal sensitivity of the skin to
    sunlight caused by certain constituents of coal-tar, but also
    sometimes by mineral oil constituents. Related to this is melanosis,
    the general darkening of the skin that may follow acute
    photodermatitis, as well as toxic melanoderma, which develop after
    long-term exposure to oils containing certain anthracene fractions.
    Both photosensitivity and melanosis rarely result from exposure to
    mineral oil.

        Hyperkeratosis may occur either together with dermatitis and oil
    acne of long standing, or in isolation -- mostly on the forearms or
    other heavily exposed parts of the body. Two forms of hyperkeratosis
    can be distinguished:  (a) circular, white and flat hyperkeratotic
    areas of a few mm in diameter, sometimes in the form of smooth
    plaques; these may occur in small clusters and are slightly raised
    above the level of the surrounding skin; and  (b) a second form,
    which may occur at the same time, and consists of rugose, pigmented
    warts that are considerably raised above the surrounding tissue level.
    The pattern is generally irregular, but may be round or oval.

        Precarcinogenic changes may be present in the hyperkeratotic
    plaques in the form of rough, slightly raised patches, which sometimes
    may take the form of horns or warts. In themselves these forms are
    still harmless, but they have a tendency to become malignant. As soon
    as these forms contain some malignant cells they are called
    keratoacanthomata. After growing for a certain period, they may be
    shed from the skin. Another form of precarcinogenic change that may be
    encountered is the shark- or shagreen-skin, a pigmented, atrophic
    skin, beset with small horns and warts.

        A basal cell carcinoma (basalioma) is a very slowly enlarging
    tumour of the skin. It may ulcerate, or invade the area round it, but,
    in general, it does not metastasize. The most common form of malignant
    tumour is the squamous cell carcinoma (spinalioma), starting as a
    small tumour, that may arise from a keratosis or in apparently healthy
    skin. It continues to grow, starts ulcerating, invades surrounding
    tissues and eventually may metastasize. None of these conditions is
    limited to mineral oil exposure. Similar changes may occur as a result
    of UV-light exposure, excessive doses of X-rays, exposure to pitch
    coal-tar, or ingestion of arsenic. A specific localization, however,
    is the epithelium of the scrotum. In this case "it is reasonable to
    assume that it could be caused by occupational exposure to soot, tar,
    pitch, or oil" (Kipling, 1968).

        A combination of various potentiating factors, such as mineral oil
    contact and exposure to sunlight (UV-radiation) increases the tendency
    to develop skin cancer (Schwartz et al., 1947; Smiley, 1951; Kinnear
    et al., 1954; Emmett, 1975). This is especially pronounced in persons
    with fair hair.  Skin carcinogenicity

        The history of the development of skin cancer as a result of
    exposure to mineral oil, as well as the major epidemiological
    literature related to the subject have been reviewed by the
    International Agency for Research on Cancer (IARC, 1973). To quote
    theft findings:

        "Volkmann (1875) described scrotal cancers among workers producing
    paraffin by the distillation of coal-tar. Subsequently, Liebe (1892)
    noted the absence of such hazard among workers exposed to pure
    paraffin. Several investigators have since shown that cancers among
    paraffin workers are not due to the paraffin but to impurities in oils
    produced during processing (Leitch, 1922; Hendricks et al., 1959).
    Refined paraffin is free of PAH and does not induce skin cancer in
    mice (Shubik et al., 1962).

        "Bell (1876) first described cancer of the scrotum in a Scottish
    shale oil worker. In a 23-year period, 49 Scottish paraffin workers
    developed skin cancer of which 13 were scrotal (Henry, 1946).

        "The cotton mule spinning industry in Great Britain originally
    used shale oil for the lubrication of the spindles (Henry, 1946). The
    first case of death from scrotal cancer in a worker who used shale oil
    in mule spinning occurred in 1923 (Bridge & Henry, 1928). In the years
    1920 to 1943, there were 1303 legally notified cases of skin cancer in
    the British mule spinning industry, including 824 of the scrotum.
    There were 575 fatal cases of scrotal cancer recorded between 1911 and
    1938 (Henry, 1946).

        "In Great Britain, the Mule Spinning Regulations have ensured that
    since 1953 only oil drastically refined with sulphuric acid shall be
    used in mule spinning and that mule spinners shall be medically
    examined every six months. These measures, together with the marked
    decline of the process of mule spinning, have produced a sustained
    fall in the incidence of cancer of the scrotum in Great Britain.

        "Cutting oils used by workers to cut metals were found to increase
    the risk of skin cancer in Birmingham, England (Cruickshank & Squire,
    1950; Cruickshank & Gourevitch, 1952), particularly among workers in
    automatic machine shops. Between 1950 and 1967, 187 cases of scrotal
    cancer occurred in this region, of which at least two-thirds could be
    attributed to oil (Waterhouse, 1971).

        "At the present time toolsetters and setter operators in automatic
    shops who use neat cutting oil have an increased risk of cancer. The
    work requires constant contact with the machines and consequent
    contamination with the oil. In the Birmingham area of England, a high
    frequency of skin and scrotal cancer from oil has occurred,
    particularly among bar automatic machine workers; but other
    engineering practices also present a cancer hazard, e.g., metal
    rolling, tube drawing, metal hardening and machine operating. Although
    the major risk is from exposure to undiluted oils, emulsions have been
    incriminated occasionally. The industries most affected are those with
    automatic shops, such as nut and bolt manufacturers. Workers have also
    been affected after exposure during the changing of transformer oil in
    electrical sub-stations and during the painting or spraying of mould
    oil for brick- and tile-making or concrete moulding, in drop forging,
    rubber mixing, wire drawing, rope making and in the jute industry and
    from grease in metal working (Kipling, 1968).

        "In France, in the valley of the river Arve in the Savoy Alps,
    there have occurred since 1955 at least 60 cases of cancer of the
    scrotum together with many cases of cancer of the skin among the bar
    automatic machine workers (décolleteurs). The very high frequency in
    the relatively small population of the valley was observed mainly
    among the self-employed and workers in small premises (Thony & Thony,
    1970). They were in contact with undiluted cutting oils.

        "Cancers of the larynx, lung and stomach have also been attributed
    to oil mist (Southam, 1928); and recently evidence has been produced
    that persons who developed cancer of the scrotum are significantly
    more liable to develop cancers at other sites, e.g., in the
    respiratory tract or upper digestive tract (Holmes et al., 1970)."

        Kinnear et al. (1954, 1955) published the results of an extensive
    epidemiological study of skin disease in jute workers in relation to
    mineral oil exposure. They found a high incidence of premalignant
    changes on the skin of the exposed parts of the body in long-term,
    older workers and isolated cases of scrotal carcinoma.

        Bingham & Horton (1966) estimated the latent period for skin
    cancer caused by mineral oil exposure to be 50-54 years (range 4-75
    years). In the case of crude paraffin oil, they mentioned an average
    of 15-18 years (range 3-35 years). In these cases, the range may be
    more important than the average, though the average indicates that, in
    general, the latent period is very long. A considerable proportion of
    the cases of skin epithelioma caused by mineral oil exposure had such
    a long latency period that the disease only appeared after retirement
    from active work (Cruickshank & Gourevitch, 1952; Kinnear et al.,

        Five cases of squamous cell carcinoma of the hand and forearm and
    one of the scrotum occurred in machine operators at a plant in
    Ontario, Canada (Mastromatteo, 1955). These workers had been exposed,
    for an average of 21 years, to cutting fluids that were subsequently
    demonstrated to be carcinogenic in animal tests (Gilman &
    Vesselinovitch, 1955).

        Milne (1970) traced 5 cases of carcinoma of the scrotum, as
    registered in the Central Cancer Registry of Victoria, Australia, and
    found that, in all cases, the carcinomas occurred during or after the
    seventh decade of life. Three of the subjects had had intensive
    contact with mineral oils throughout theft working life, one was a
    stoker in a gas-works, and the fifth had always been involved in
    administrative work.

        In the Netherlands, a recent survey demonstrated that scrotal
    cancer occurred only sporadically and was not correlated with
    occupational exposure to mineral oil (Pruyn & Reijnierse, 1972;
    Fokkens et al., 1972; van Raalte, 1972).

        Eight cases of scrotal cancer were discovered by Avellan et al.
    (1967), over a period of 24 years, among 250 automatic lathe operators
    in Gothenburg, Sweden. Diagnosis was made when the operators were
    between 54 and 66 years of age and after periods of exposure to
    mineral oil ranging from 19 to 43 years. In the words of the authors:

        "All of the cases occurred among operators who began their work
    during the era when the exposure, as a result of the prevailing
    machine construction, was considerable and before the regulations and
    the controls, which were instituted after the discovery of the first
    cases, had been set up."

        Wahlberg (1974) analysed 34 cases of scrotal cancer reported to
    the Swedish Cancer Registry between 1958 and 1970. Seven cases (21%)
    had been heavily exposed, occupationally, in the past to oil. and oil
    mist, e.g., as automatic lathe operators. One of this group developed
    a primary lung cancer.

        A retrospective study of 298 cases of scrotal cancer registered in
    the Birmingham region in the United Kingdom between 1936 and 1972 was
    reported by Brown et al. (1975). The incidence of scrotal cancer was
    5-6 cases per million males per year, whereas for the whole of the
    United Kingdom, the incidence is 1-2 cases per million males per year.
    The patients or relatives were interviewed in 109 cases: 94 had been
    exposed to mineral oil (mainly tool-setters and machine operators, and
    all cases had been exposed to cutting oil, 14 had been exposed to
    pitch or tar, and, in 7 cases, there was no apparent occupational
    exposure. In 298 cases of scrotal cancer, 52 other primary rumours
    were noted; of these, 42 arose following the scrotal cancer including

    15 skin tumours and 12 bronchial tumours. The incidence of both these
    types of cancers was much in excess of what would be expected
    statistically. The majority of the group with second primary tumours
    were machine operators and tool-setters (75% in the case of bronchial
    carcinoma). The authors postulated that in these cases both primary
    rumours were initiated by the same carcinogen.

        After studying all the available literature, Desoille et al.
    (1973) concluded that, in general, and with the exception of certain
    extreme situations, the number of tumours caused by exposure to
    mineral oils was low. According to Auld (1950) and Eckhardt (1957),
    though certain cutting oils and other mineral oils are carcinogenic to
    the skin, the degree of carcinogenicity is very low compared with that
    of coal-tar, pitch, and shale oil. In their opinion, and that of most
    other authors, e.g., Avellan et al. (1967), even this level of
    carcinogenicity would disappear, if a minimum of industrial and
    personal hygiene measures were adhered to. On the other hand, Auld
    (1950), Desoille et al. (1973), Thony et al. (1975) and many others
    urge that alternative products should be developed that do not expose
    the workers to a tumorigenic hazard.

        In a further report on the skin cancer epidemic in the French Arve
    Valley, Thony et al. (1975) recorded 133 epithelioma cases in 15
    years, mostly of the scrotum. The incidence in these workers was 36
    times that expected in the general population. In workers in small
    workshops with poor industrial and personal hygiene, the incidence was
    found to be 3 times higher than in the larger plants. The average age
    was 54 years (range 35-75 years) and the average exposure 30 years
    (range 15-50 years), at the time of clinical diagnosis. In addition,
    an increased incidence of bronchopulmonary tumours was found,
    especially in the  décolleteurs. Officially until 1947, but in
    practice possibly until 1950, coaltar-derived anthracene oils were
    used, which originally contained benzo(alpha)pyrene levels of up to
    1000 mg/kg. The level was later reduced to 10 mg/kg. These oils may be
    responsible for many of the previously mentioned cases, but skin
    cancer also occurred in some of the workers exposed only to the
    petroleum-derived oils that were used exclusively later on. Fresh
    cutting oils, as delivered to the users, contained benzo(alpha)pyrene
    levels ranging from 0.5 to 145 µg/litre and the concentration of
    carcinogens was found to increase during use, though not to the same
    extent as that in quenching oils (2-100 times with an average of 30
    times), and in lubricating oils for internal combustion engines.  Effects of oil mist exposure

        Southam (1928) was the first to attribute cancers of the larynx,
    lung, and stomach to oil mist exposure.

        In a report by Huguenin et al. (1950), 32 out of 144 patients with
    lung cancer had been in prolonged and intense contact with oil mist in
    the past. Old metal-working machines with improper protection against
    oil mist, processes where oil vapour arose from contact with hot
    metal, and high-pressure cleaning of machines with oil, were found in
    the places where these patients had worked. Hendricks et al. (1962)
    considered the observations of Huguenin et al. (1950) to be of
    doubtful significance in view of the high incidence of this disease in
    non-oil-mist-exposed groups. Nevertheless, the conditions in these
    cases may have been such, that a causal relationship, in at least some
    of them, cannot altogether be excluded.

        More printing industry workers were found among cases of bronchial
    carcinoma in a Stockholm clinic (8 out of 125) than would have been
    expected (Ask-Upmark, 1955). Certain industrial processes where oil
    mist might occur were studied by Hendricks et al. (1962), who gave an
    indication of possible exposures in their table of actual exposures
    measured in various industries (Table 7).

        The average particle size in the oil mists varied according to the
    generating process and was found to be about 1.0-5.0 µm.

        In 241 Kodak workers exposed to oil mist (Ely et al., 1970), no
    significant differences were found, either in mortality, respiratory
    symptoms, and disease, or in lung function compared with a control

        In the same year, Holmes et al. (1970) produced evidence, that
    persons who developed cancer of the scrotum were significantly more
    liable to develop cancers of the respiratory tract and the upper
    digestive tract.

        Similar findings have been reported in a preliminary paper by
    Waterhouse (1972). An excess of primary tumours at other sites (skin,
    respiratory and upper alimentary tracts) was found in men with scrotal

        From animal studies, it appears that oil mist particles larger
    than 5 µm will not easily penetrate into the lungs, but will be
    retained mainly in the nasopharynx and upper respiratory tract.
    Smaller particles, especially those of 2.5 µm and less, will readily
    pass into the alveoli, where they will be phagocytosed and passed on
    to the lymph nodes. When this mechanism cannot cope with the

    situation, in cases of continuously repeated high exposure to oil
    mists, a chemical pneumonitis and chronic lipid pneumonia may develop
    (Proudfit et al., 1950; Foe & Bigham, 1954), but this appears to be an
    extremely exceptional condition. Clinical details and examples of this
    will be discussed in section 4.8.

    TABLE 7.  Exposure to oil mist in selected industries

    Type of industry                 Observations   Exposure range
                                                    oil mist mg/m3

    brass and aluminium production       5          1.4-20.7
    copper mining                        7          5.4-22.0
    automobile manufacture              37          1.0-56.5
    manufacture of steel products       33          0.8-50.0
    newspaper (press room)               8          2.0-16.6
    screw manufacture                    6          1.0-14.2

    From: Hendricks et al. (1962).

        In 12 out of 19 workers with oil mist exposures ranging from 9 to
    18 years, Jones (1961) found a marked linear and reticular pattern in
    the radiograms of the lungs. Exposures ranged from 1 to 9 mg/m3 with
    70% of the particles of the order of 1 µm.

        Various groups of research workers have studied different aspects
    of the printing industry. Printing-ink consists chiefly of a
    suspension of carbon black in mineral oil or aromatic extracts of
    mineral oil. Modern high-speed newsprint presses can generate fairly
    high concentrations of ink-mist aerosol. Most particles, however, are
    outside the respirable range and may end up in the stomach, rather
    than in the lungs of exposed workers. Lippmann & Goldstein (1970)
    found an average droplet size of 14 µm (ranging up to 30 µm) in the
    press rooms of the New York Times. The time-weighted average
    concentration of respirable mist particles was found to be 1.4 mg/m3
    against a total time-weighted average mist concentration of
    8.6 mg/m3. In a parallel epidemiological study in the same firm,
    mortality and morbidity data over a 15-year period were compared for
    pressmen and compositors. No significant differences in respiratory
    mortality or morbidity were found (Goldstein & Benoit, 1970).

        In a similar study by Pasternak & Ehrlich (1972), there was no
    increase in respiratory symptoms or decrement in respiratory
    performance in 778 New York pressmen compared with 1207 compositors.
    No significant differences in death rates, were found in those who
    were less than 40 years old when first employed, even if they had
    worked for more than 20 years. In those first employed when they were
    more than 40 years old and with more than 20 years of employment,
    there was a significantly higher death rate in pressmen compared with
    compositors. The reason for this finding was not clear. The mean oil
    mist concentration measured in the 3 workshops concerned was
    3.7-5.2 mg/m3.

        Moss et al. (1972) analysed the causes of death of 3485 former
    full-time printing industry workers from London and Manchester, who
    died in the period 1952-66; Greenberg (1972) studied the death
    certificates of 670 male printing workers who died between 1954 and
    1966. In both studies, an excess number of cancers of the lung and
    bronchus were found. This excess was more marked in Manchester and
    greatest in machine-room men. The authors concluded that the slight
    excess found might or might not be due to occupation. They considered
    that an occupational cause was more likely in the case of the greater
    excess in the Manchester machine-room men.

        These studies in the printing industry have been mentioned in
    relation to mineral oil exposure. However, the same data could be
    related to carbon black and even to lead exposure. Similar
    considerations should be kept in mind in the evaluation of the data in
    other occupations where many other factors might also play a role,
    either individually or combined with the mineral oil used, as, for
    instance, chromium in the metal-working industry.

        In studies in 34 metal-working firms in Baden-Würtemberg (FGR),
    the frequency of respiratory complaints (cough, expectoration, and
    dyspnoea) in 443 workers exposed to oil mist for long periods was
    compared with that in 398 unexposed controls, matched for age. Mineral
    oil mist exposures from cutting oils had ranged from 40 to 150 mg/m3
    over long periods. The highest incidence of complaints was found among
    unexposed smokers, the lowest incidence amongst non-smoking,
    oil-mist-exposed workers. The authors did not find any signs of
    irritative effects from oil-mist exposure, but a significant
    protective effect against the well-known irritant effects of smoking
    (Drasche et al., 1974). This finding is in line with findings in
    experimental animals, that previous exposure to oil mist reduces the
    lethal effects of respiratory oxidants such as ozone and nitrogen
    dioxide in mice (Wagner et al., 1961). The authors stated that
    conclusions could not be drawn from this study in relation to the
    carcinogenicity of these oil mists in the respiratory tract.

        During the cold processing of metal, the concentration of mineral
    oil mist in the air (spindle oil aerosol) fluctuated from 3 to
    40 mg/m3 (on average 10 mg/m3). During an examination of 77 lathe
    operators (men and women), functional disturbances found to occur in
    the respiratory system, in particular after a period of service of
    more than 10 years, included a reduction in the active volume and the
    maximum ventilation of the lungs and an increase in oxygen requirement
    and in its coefficient of utilization (Bruskin & Demcenko, 1975).

        A 30-year retrospective cancer mortality study was carried out by
    Decoufle (1976) on 5189 workers engaged in metal-working for at least
    one year. No significant differences in cancer mortality were
    observed, when compared with the general population. Indications of
    increased incidences of respiratory and digestive cancer, observed
    when comparison was made on an age group or exposure basis, were not
    statistically significant.

        Decoufle (1978) published a further study on a group of 2485 male
    workers employed between 1938 and 1967 in jobs exposing them to
    various levels of cutting oil mists. Compared with the total death
    rate of the US male population, no significant differences were
    observed for 15 cancer site categories. However, a 2-fold risk of
    cancers of the stomach and large intestine (combined) was seen after
    20 years of follow-up in the subgroup of men with 5 or more years'
    exposure to cutting oil mists, prior to 1938. Deaths from nonmalignant
    respiratory disease were significantly fewer than expected. These
    results suggested that occupational exposure to soluble and insoluble
    cutting oil mists, during various metal machining processes, did not
    pose a health hazard in terms of respiratory cancer and fatal
    nonmalignant respiratory disease, but might be associated with certain
    forms of gastrointestinal cancer.

        To summarize, it can be concluded from the literature that
    oil-mist exposure can give rise to pulmonary disease, but only after
    prolonged exposure in workplaces with unsatisfactory hygienic
    conditions. If oils with a low content of polynuclear aromatic
    hydrocarbons are used in situations where oil mists can be generated
    and the TLV for oil mists is not exceeded, this problem is unlikely to

    4.8  Clinical Studies

        Clinical studies on the effects of mineral base oils and products
    derived from them on the skin have been discussed together with
    epidemiological studies in sections and It was felt,
    that compilation of individual case-histories from the literature on
    this subject was superfluous. Adverse effects resulting from the
    surgical use of paraffin for cosmetic purposes, and those following
    grease-gun accidents have not been considered in this review.

        Clinical studies on the effects of these products after ingestion
    show that the main effects are caused by aspiration, which may be a
    complication of ingestion, and usually occurs during subsequent
    spontaneous or induced vomiting. Otherwise, there is general agreement
    that mineral base oils, lubricating oils, and greases have a low order
    of toxicity, when ingested (Gerarde, 1960). At the most, some
    gastrointestinal symptoms, such as abdominal cramps and diarrhoea,

        There was evidence from a clinical case study that prolonged
    ingestion of mineral oil over a number of years could result in oil
    deposition in the small intestine, abdominal lymph nodes, liver, and
    spleen and lungs. This produced significant structural and functional
    abnormalities that were considered to have contributed to the
    patient's death (Nochomovitz et al., 1975).

        White mineral oil (pharmaceutical grade) is a base oil
    specification intended for oral use. It is a highly purified base oil
    distillate, mainly containing saturated paraffinic fractions, and it
    has to be free of polynuclear aromatic hydrocarbons. It is used as a
    laxative, in pharmaceutical formulations, and as a food-grade
    lubricant. From studies with radio-opaque oil, it appears possible
    that a small amount of mineral oil, when taken orally as a laxative
    just before retiring, may gain entrance into the lungs. Though this is
    not of any consequence if it occurs only once, a cumulative effect in
    the lungs might result, if it occurs repeatedly, day after day, over
    several years (Sante, 1949; Miller et al, 1962).

        Clinical experience of the effects of inhalation of mineral oil in
    the lungs is in agreement with the results of animal studies (section In man, mineral oil is rapidly phagocytosed and transferred
    to the regional lymph nodes. In contrast with vegetable oil and oil of
    animal origin, however, mineral oil cannot be metabolized and is
    deposited in the interstitial tissue and in the lymph nodes, where it
    induces a cellular reaction, with the appearance of giant cells that
    may result in fibrosis of more or less extensive lung areas. The
    resulting clinical and pathological picture depends to a large extent
    on whether there has been massive, acute over-exposure, with the
    body's defence mechanisms overwhelmed (see (a)), or whether long-term,
    low-level exposure has occurred, where the defence mechanisms can cope
    with the daily exposure and no disease will become apparent, until the
    signs and symptoms of the secondary fibrotic reaction appear (see
    (b)), (Pinkerton, 1927, 1928; Cannon, 1940; Freiman et al., 1940; Moel
    & Taylor, 1943).

        A few typical clinical entities can be recognized:

         (a) Diffuse acute mineral oil pneumonia is practically always
    the result of an accidental massive aspiration of mineral oil (Sante,
    1949; Proudfit et al., 1950; Weissman, 1951; Foe & Bigham, 1954;
    Gerarde, 1960). It is, in fact, a chemical pneumonitis frequently with
    a superimposed secondary infection, progressing into an interstitial
    proliferative inflammation. Cases resulting from aspiration following
    accidental ingestion of products containing gasoline, kerosene, or
    other petroleum solvents in the same boiling-range are well-known from
    the clinical literature. Many cases have occurred as a result of
    aspiration of seawater contaminated with diesel oil by survivors of
    sinking ships (Weissman, 1951).

        Aspiration of mineral oils in the boiling-range under discussion
    may have similar results. This can happen when choking occurs, while
    taking white medicinal oil. This acute type of mineral oil pneumonitis
    is not likely to occur as a result of occupational exposure to oil
    mist. Clinically, all signs and symptoms of an acute massive
    pneumonitis are present with elevated temperature and a chest X-ray
    typical for this condition. Oil droplets may be found in the sputum
    and, histologically, the condition is characterized by intra-alveolar
    accumulation of oil-laden phagocytes and inflammatory cells. Acute
    mineral oil pneumonia is a special form of lipoid pneumonia, which
    presents a similar clinical picture and is the result of aspiration of
    vegetable or animal oil (mainly cod liver oil, but also egg-yolk and
    milk). Though in these cases a similar severe acute pneumonia may
    develop, the oil can be metabolized and disappears completely after a
    certain time (Sante, 1949). With oils of animal origin, such as cod
    liver oil, however, the reaction of the body (lungs and other internal
    organs) can be much more serious than with mineral oils (Young et al.,

         (b) Diffuse chronic mineral oil pneumonia occurs as a result of
    gradually developing fibrotic and proliferative changes in both lungs.
    It may follow years after the acute form, or without an acute
    beginning after a long, practically asymptomatic period as a result of
    repeated smaller "aspirations", such as those resulting from regular
    massive use of mineral-oil-based laxatives, nose-drops, or nose-sprays
    (Pinkerton, 1927; Bishop, 1940; Freiman et al., 1940). The apparently
    rare cases of mineral oil pneumonitis following prolonged occupational
    exposure to excessive oil mist concentrations fall into this category
    (Sante, 1949; Proudfit et al., 1950; Weissman, 1951; Foe & Bigham,
    1954; Gerarde, 1960). Reports from the literature suggest that in some
    of these cases, at least, a predisposing factor was present in the
    form of a pre-existent or concomitant lung disease (Freiman et al.,
    1940; Weissman, 1951; Forbes & Markham, 1967). Increasing dyspnoea and
    productive cough are the most important symptoms. The chest X-ray

    generally shows increased perihilar opacities with signs of lung
    fibrosis and diffuse patchy opacities. Oil droplets or oil-laden
    phagocytes may be found in sputum or in tissue derived from lung
    biopsy (Goodwin, 1934; Bishop, 1940; Freiman et al., 1940; Rossier &
    Bühlmann, 1949; Sante, 1949; Proudfit et al., 1950; Borrie & Gwynne,

         (c) Paraffinomas are large fibrous nodules or globules of liquid
    mineral oil embedded in dense hyaline fibrous tissue. They represent a
    separate form of the chronic mineral oil pneumonitis in which
    oil-laden phagocytes, destroyed by pressure, atrophy in the fibrous
    scar tissue formed. Paraffinomas may be found singly or in clusters
    around the large bronchial branches or at the site of the hilar lymph
    nodes. It may be difficult to differentiate a paraffinoma from a lung
    tumour radiologically (Brown & Biskind, 1941; Wood, 1943; Sante, 1949;
    Proudfit et al., 1950; Weissman, 1951; Bryan & Boitnott, 1969; Borrie
    & Gwynne, 1973). Aspiration biopsy may help in the differential
    diagnosis (Nathanson et al., 1943).

        Boitnott & Margolis (1966a) have described analytical methods for
    the identification of the various oils in human tissues. Mineral oil
    droplets may pass from the hilar nodes via the thoracic duct into the
    systemic circulation (Pinkerton, 1927; Young et al., 1939; Freiman et
    al., 1940; Boitnott & Margolis, 1966b). As a result of this
    transmission, oil droplets have been found in the liver, spleen, and
    other organs (Pinkerton & Moragues, 1940; Rewell, 1947).

        The general pattern found in young children is slightly different
    from that found in adults. Pinkerton (1927) described 6 cases of
    lipoid pneumonia in children and data on 25 cases in children have
    been summarized by Goodwin (1934). Seven cases have been reported by
    Ikeda (1935) and 27 cases by Bromer & Wolman (1939). There is general
    agreement that fats and oils of animal origin play a more important
    role than mineral oil in lipoid pneumonia in infants and young
    children. Furthermore, the acute massive aspiration type is more
    frequently seen in children than the chronic form. The main causal
    factors in these observations are: false passage of a gavage tube,
    false deglutition in bottle-feeding with the baby lying on its back --
    especially in cases of debilitating disease, and also aspiration
    following forced administration of milk or cod liver oil with or
    without vomiting or choking (Freiman et al, 1949).

        With regard to adults, Ikeda (1937) summarized 106 cases from the
    literature, Graef (1939) 22 cases, Bishop (1940) 136 cases, Freiman et
    al. (1940) 58 cases, and Moel & Taylor (1943) 20 cases. They concluded
    that lipid pneumonia, especially the diffuse chronic form, occurs more
    frequently in adults than is generally believed. Liquid paraffin is by
    far the most important etiological agent in the adult. Debilitated

    states, dysphagia and impaired cough reflexes, because of neurological
    or other disorders, are important predisposing factors. The authors
    stress, however, that mineral oil is widely used without evident harm,
    even in elderly persons. Wherever there is a real indication for this
    type of medication, they see no reason to discontinue it. Extensive
    use, especially self-medicated, of liquid paraffin intranasally or via
    the oral route by debilitated or dysphagic patients should, however,
    be discouraged (Bishop, 1940; Freiman et al., 1940).

        As a matter of interest, a few cases of lipoid pneumonia have been
    described in relation to the intratracheal administration of
    mineral-oil-based mixtures by opera singers, prior to every
    performance on the stage, in order to improve the quality of the voice
    (Even, 1947; Facquet & Langeard, 1947; Meyer, 1976). A similar case
    was described by Garvin (1939) as a result of intratracheal

        From the literature, it is apparent that with the recognition of
    the causal factors and the change from oil-based to water-based
    nose-drops, the incidence of the type of lipid pneumonia just
    described has drastically decreased, since the end of the forties.

        The following more or less typical cases, in which there was -- or
    might have been -- a relation between occupational exposure to oil
    mist and the occurrence of lipid pneumonia, were found in the
    literature. Proudfit et al. (1950) reported a case of chronic lipid
    pneumonia in a 40-year-old man who had been spraying mineral oil for
    17 years; he had a typical chest X-ray. The chief complaints were
    cough, shortness of breath, and fatigue. Mineral oil droplets were
    identified in the sputum; 3 years later the condition had progressed
    slightly. A case of lipid pneumonia was described by Weissman (1951)
    in which the disease apparently developed on the basis of
    long-standing pulmonary fibrosis as the result of blast-spraying of
    machine parts with mineral oil; no mask had been used as protection
    against the inhalation of nebulized oil. Foe & Bigham (1954) reported
    the case of a 30-year-old aircraft mechanic who complained of fatigue,
    shortness of breath on exertion, and frequent chest colds. Lipid
    pneumonia was diagnosed from a lung biopsy. The mechanic had been
    spray-cleaning aircraft engines with a mixture of 50% kerosene and 50%

        Two cases of progressive respiratory disease, which developed in
    the fifth decade of life were described by Forbes & Markham (1967).
    Both patients had a moderate to heavy smoking history; one, in
    addition to this, had a family history of asthma; dyspnoea and
    wheezing were the major signs in each case. Both reacted well to
    treatment, but recurrence of signs and symptoms was related to working
    with cutting oils, the composition of which was not mentioned.

        The epidemiological data on the possible relationship between
    cancer of the respiratory tract and long-term occupational exposure to
    oil mist has been discussed in section There is some evidence
    that in cases where an unsatisfactory industrial hygiene situation
    coincided with the use of an oil with probable carcinogenic
    properties, such a causal relationship might exist. On the other hand,
    various extensive studies have shown that, in general, it is certainly
    not a major problem.

        However, Wood (1943) reported a fatal case of extensive lipid
    pneumonia in a house-maid who had used oily nose-drops in large
    quantities for recurrent sinusitis over a period of 10 years. At
    postmortem, an alveolar-cell carcinoma was found in the lungs. The
    author suggested that there might have been a causal relationship
    between the 2 diseases, though he assumed that this occurrence would
    be rare. Two cases of bronchogenic carcinoma were described by Sante
    (1949). In the first case, the malignant epithelial tumour was
    situated in an area of dense fibrotic tissue, typical of a
    paraffinoma. In the other case, a squamous cell carcinoma was found
    together with lipid pneumonia in an early stage of organization. The
    author felt that there might have been an etiological relationship in
    the first case, but considered this less likely in the second case.
    Both patients had taken a tablespoon of mineral oil as a laxative,
    just before retiring, for years. Volk (1964) studied a series of more
    than 100 cases of mineral oil pneumonia and noted that not one case of
    bronchogenic carcinoma occurred in this group. In addition, he
    reviewed 114 consecutive autopsies of adenocarcinoma of the lung in
    which he did not find any lesions that might be associated with
    mineral oil pneumonia.

        A rapidly lethal case of multifocal alveolar cell carcinoma of the
    lung was reported in a 63-year-old man who had centrifuged used
    cutting oil for 23 years and had been exposed continuously to oil mist
    of this type during that period (Despierres et al, 1965). Wahlberg
    (1974) described one case of primary lung cancer in 7 men who
    developed scrotal cancer following heavy occupational exposure to oil
    and oil mist in, for example, automatic lathe operation. A case in
    which achalasia led to chronic mineral oil pneumonia was reported by
    Bryan & Boitnott (1969). An adenocarcinoma developed in the area of
    scarring resulting from the mineral oil and caused death. On the basis
    of a literature study and theft own findings, the authors concluded
    that the pathogenesis might be related to the pulmonary scarring
    rather than directly to the mineral oil (see also Yokoo & Suckow,
    1961). However, the authors also considered that there was no reason
    to suppose that carcinomas were more likely to arise in a scar induced
    by mineral oil than in a scar of a different origin (Bryan & Boitnott,

    5.  BITUMEN

    5.1  Properties and Analytical Methods

    5.1.1  Chemical and physical properties

        The term bitumen is applied to solid and semi-solid residues from
    the distillation of suitable crude oils. This product is known as
    "asphalt" in the USA. In most other countries, the term asphalt is
    reserved for certain natural deposits and for mechanically made
    mixtures of bitumen and mineral matter.

        Bitumen is the residue obtained by atmospheric and vacuum
    distillation of certain types of crude oil. It is generally a black or
    dark-brown material, ranging from a highly viscous liquid to a solid
    and brittle substance at normal ambient temperatures, depending on the
    proportion of light fractions removed. On heating, bitumen softens
    gradually and eventually becomes fluid. Grades are characterized by
    their "penetration" and "softening" point. According to the Petroleum
    Handbook (1966), bitumen can be considered as a colloidal system of
    highly condensed aromatic particles in an oil with ring-type
    molecules. From this statement, it is clear that bitumen is a very
    complex mixture of mainly high-boiling hydrocarbons. Its composition
    varies widely with the geographical source of the crude oil and the
    process of manufacture. For example, a mixture of 6 samples was found
    to contain:

    (a) 32% asphaltenes: high-relative-molecular-mass aromatic compounds
        and heterocyclic hydrocarbons of which some are unsaturated. They
        are soluble in carbon disulfide but insoluble in petroleum

    (b) 32% resins: polymers resulting from the processing of unsaturated

    (c) 14% saturated hydrocarbons: hydrocarbons in which the carbon atoms
        are connected by a single bond; and

    (d) 22% aromatic hydrocarbons: hydrocarbons containing one or more
        benzene rings per molecule, including condensed polycyclic
        aromatic hydrocarbons (Simmers et al., 1959; Simmers, 1964).

        While the appearance and engineering applications of bitumens and
    asphalts are similar to those of coal-tars and pitches, fundamental
    differences exist between these 2 classes of materials (Puzinauskas &
    Corbett, 1978). Bitumen is generally derived from crude oil by a
    process that does not involve cracking or thermal conversion, and
    coal-tars and pitches are obtained by high-temperature carbonization
    of bituminous coal. Chemically, coal-tar materials are mainly composed

    of highly condensed-ring aromatic and heterocyclic hydrocarbons.
    Bitumens, on the other hand, contain a much higher proportion of high
    relative molecular mass paraffinic and naphthenic hydrocarbons and
    their derivatives. Under comparable heating during application and
    use, coal-tars generate substantially higher emissions of polynuclear
    aromatic hydrocarbons than bitumen. While epidemiological surveys of
    workers engaged in the production of coal-tar have revealed an
    increased incidence of lung cancer, no increases in cancer or other
    adverse effects have been observed in studies on workers involved in
    the manufacture and application of asphalt.

        The benzo(alpha)pyrene content of petroleum bitumens derived from
    various Russian crude oils was determined by Janyseva et al. (1963).
    They demonstrated that the benzo(alpha)pyrene content of straight-run
    bitumen was considerably lower (of the order of 0.6 mg/kg) than that
    of bitumens derived from cracking residues (of the order of
    4-272 mg/kg). Schamp & van Wassenhove (1972) reported
    benzo(alpha)-pyrene levels of 3-5 mg/kg in bitumens.

    5.1.2  Methods of sampling and analysis

        See section 2.1.2.

    5.2  Sources of Environmental Pollution

    5.2.1  Natural sources

        Natural bitumen and asphalt deposits occur in various parts of the
    world, mainly as a result of mineral oil seepage from the ground. The
    most well-known natural asphalt deposit is the Trinidad Lake, which
    contains a mixture of about 39% bitumen, 32% mineral matter, and 29%
    water and gas.

    5.2.2  Man-made sources  Production

        Total world-wide bitumen production reached 90 million tonnes in
    1973. As with crude oil, this was approximately 10 times the immediate
    pre-war level. Bitumen production rose to 100 million tonnes in 1979
    and is expected to continue to increase in the future, although at a
    lower rate of growth than in the past.

        The following types of bitumen are produced by refining and

    "Straight" bitumen

        The residue of atmospheric or vacuum distillation of
    asphaltic-based crude oils. For special applications, very hard
    pitch-type bitumen residues can be obtained by distilling cracked

    "Blown" bitumen

        Manufactured by feeding air-bubbles countercurrent through a
    column of hot molten straight bitumen. Oxidation reactions occur
    leading to dehydrogenation and polymerization of the unsaturated and
    aromatic components. In this process, large condensed aromatic nuclei
    may also formed.

    "Cutback" bitumen (or more fluid bitumen grades)

        Obtained by mixing bitumen with petroleum solvents or mineral oil,
    sometimes with coal-tar or high aromatic extracts.

    Bitumen emulsion

        Made by emulsifying 50-65% of bitumen in water in the presence of
    0.5-1.0% of an emulsifier, usually soap and generally used cold for
    both roadmaking and industrial purposes.  Uses

        The main use of bitumen is for paving roads. It is also used in:

    (a) lining irrigation canals, water reservoirs, dams, and dykes;

    (b) mastic asphalt for industrial flooring;

    (c) bituminized felts for roofing;

    (d) protective coatings, for walls, motor-cars, water mains;

    (e) adhesives for the building industry;

    (f) coal briquetting;

    (g) electrical insulation; and

    (h) battery-making.

    5.3  Environmental Exposure Levels

        Apart from walking or riding on bituminous pavements and roads,
    the general population will not normally come into contact with
    bitumen, except in the form of protective coatings and coal
    briquettes. On the other hand, the general population can, on
    occasion, be exposed to fumes from heated bitumens for short periods
    of time during road-building or the covering of roofs. Emissions from
    asphalt roads have been mentioned in the literature as a possible
    source of exposure for the general population, but such exposure is
    considered to be as negligible. Recent evidence from the Federal
    Republic of Germany and the USA confirms this (Hettche, 1963).

        Occupational exposure to bitumen may be much more intensive in
    certain professions and may range from accidental splashing with hot
    bitumen to repeated and prolonged contact of the skin with the more
    liquid bitumen grades or to exposure to fumes from heated bitumen.

    5.4  Environmental Distribution and Transformation

        No specific data relating to bitumens are available in relation to
    distribution among media, environmental transformation and
    degradation, interaction with physical, chemical, or biological
    factors, and bioconcentration. On the other hand, there is a lot of
    information on the microbial degradation of individual petroleum
    hydrocarbons (section 3.4).

    5.5  Metabolism

        Uptake and storage of the light fractions contained in bitumens
    may occur; however, no specific data exist on this subject.

        Bitumens occur in a variety of commercial products. The
    composition of these products may vary widely depending on the
    geographical origin of the crude oil used and the manufacturing
    process applied. These facts may influence the results of metabolic
    studies, all of which are concerned with the exposure of experimental
    animals. Human data are lacking.

    5.6  Effects on Experimental Animals

    5.6.1  Short-term exposure

        No data are available on acute toxicity, exposures related to
    adverse effects, interactions, and species comparisons. It is
    generally accepted that the acute toxicity of bitumens is low.

    5.6.2  Long-term exposure

        No data appear to have been published on toxic effects in specific
    organs, teratogenicity, or reproduction. The data on mutagenicity are
    limited. On the other hand, substantial experimental work has been
    carried out concerning the carcinogenic effects of bitumens on skin.

        Twort & Fulton (1930) examined the carcinogenic effects of various
    synthetic tars and their fractions on the skin of mice. The
    carcinogenic activity varied according to the compound used and with
    the temperature of pyrolysis. Results of these studies confirmed the
    earlier finding of Kennaway (1925), that the temperature at which the
    tar formed was an important factor in the production of carcinogenic
    substances. Cancer of the skin of mice was induced by applications of
    the synthetic residues obtained from heating substances such as
    acetylene, isoprene, a noncarcinogenic petroleum, yeast, and human
    skin. The yield of carcinogens decreased when carbonization had
    occurred at temperatures above 950°C. The yield was greatest between
    850 and 870°C; less between 600 and 750°C, and negligible at 500°C.
    Furthermore, the authors found that the carcinogenic activity of the
    synthetic residues could be reduced considerably by oxidation or
    reduction (by various methods) or by dilution with oleic acid.

        A wide range of aliphatic and simple aromatic hydrocarbons were
    pyrolysed by Badger (1962), who showed that polynuclear aromatic
    hydrocarbons were formed from simpler hydrocarbons at 700°C via
    primary radicals formed by carbon-hydrogen and carbon-carbon fission
    (cracking) at this elevated temperature. The same process occurred to
    a much lesser extent at 550°C.

        According to Bogovski et al. (1963), thermal distillation of a tar
    to coke decreased the carcinogenic activity by the formation of
    irreversible condensation products from polynuclear aromatic
    hydrocarbons, together with other high molecular compounds. In
    long-term, skin-painting experiments on white mice, the authors showed
    that such a coking process reduced the tumour incidence from 68% to
    3.7% in the case of shale-oil tar. As shale-oil tars have a much
    higher carcinogenic activity than petroleum residues (Twort & Twort,
    1931), it might be expected that coking of petroleum residues would
    reduce the carcinogenicity of the material still further.

        The carcinogenic effects of bitumen on the skin of C-57 black mice
    was studied by Simmers and co-workers (1959). In a first series of
    tests, they used a mixture of 6 samples from Southern Californian
    refineries, in which both steam- and aft-blown bitumens were mixed.
    Painted twice weekly on the skin for a lifetime, the mixture caused 12
    dermoid carcinomas in 68 animals, compared with none in the untreated
    control group. Formation of cancer was preceded by hair loss, dryness
    and scaling of the skin, and papilloma formation. After subcutaneous
    injection, 8 sarcomas occurred in 62 animals at the site of injection
    compared with none in the control group. However, the relevance of
    results from such subcutaneous studies is questionable.

        In an inhalation study on the same pooled sample and using the
    same strain of mice, the animals inhaled an aerosol of bitumen
    droplets suspended in moist air for 30 min/day, 5 days per week, for
    up to nearly 17 months (Simmers, 1964). Changes found on microscopic
    examination were minimal and included occasional congestion, acute
    bronchitis, pneumonitis, bronchial dilatation, and some peribronchial
    round-cell infiltration. In a second inhalation study, the animals
    were exposed to cooled smoke from bitumen at 120°C for 6-7´ h/day, 5
    days a week, for up to 21 months. In this study, peribronchial
    round-cell infiltration, bronchitis, pneumonitis, abscess formation,
    loss of cilia, epithelial atrophy, and necrosis were more common.
    Squamous cell metaplasia was rare, but hyperplasia was more commonly
    seen. The changes in both experiments were patchy, rather
    non-specific, and similar to those described as a result of exposure
    to other air pollutants.

        In his next series of tests, Simmers (1965a) compared the
    carcinogenicity of straightrun and air-blown bitumen in prolonged
    regular skin application tests and after single or repeated
    subcutaneous injection. Undiluted air-blown bitumen did not induce
    tumours, when applied to the skin, probably because the bitumen was
    too hard; when dissolved in toluene the incidence of skin cancers
    increased to 45%. This may be the result of better contact with, or
    penetration into the skin. On the other hand, the polynuclear aromatic
    hydrocarbons might be concentrated by the solvent. In a similar
    skin-painting study with straight-run bitumen, skin cancers occurred
    in only 14%. The same trend was apparent after subcutaneous injection,
    where 0 and 13% tumours were found at the site of injection with
    straight-run and air-blown bitumen, respectively. The author presumed
    that this difference in response resulted from a difference in
    chemical composition. Although the aromatic fraction of air-blown
    bitumen was lower than that of straight-run bitumen, it contained more
    complex aromatic hydrocarbons due to polymerization and condensation
    caused by the air-blowing.

        Straight-run bitumen was separated into 4 fractions, which were
    painted 3 times a week, continuously, on the skin of the same strain
    of mice (Simmers 1965b). The fraction containing most of the saturated
    compounds and aromatic hydrocarbons -- which also showed practically
    all the UV light fluorescence -- induced considerably more skin
    rumours (43.3%) than straight-run and air-blown bitumens had done in
    earlier studies. The author pointed out that, though fluorescence was
    not a guarantee of carcinogenic activity, polynuclear aromatic
    hydrocarbons known to be carcinogenic are fluorescent. In this
    context, both Kennaway & Heiger (1930) and Berenblum et al. (1947)
    suggested that these compounds -- even in very small quantities --
    might be discovered by this method. The 4 bitumen fractions used in
    the previous study were injected subcutaneously -- once or repeatedly
    -- in the same strain of mice, at various doses (Simmers, 1966). A
    variety of benign and malignant tumours resulted, both at the
    injection site and in distant organs. The dose seemed to be more
    important for tumour formation than the duration of exposure.

        Hueper & Payne (1960) compared the carcinogenicity of various
    petroleum products and coal-tar in long-term tests on mice, rats, and
    guineapigs. Four road-bitumens of different geographical and
    manufacturing origin were applied to the skin of, or injected
    intra-muscularly into, mice and rats. In some of the test-animals,
    tumours were found at the site of application. Fumes from heated
    coal-tar and from a blown bitumen used as a roofing bitumen did not
    induce cancers of the lungs in rats and guineapigs in inhalation
    experiments lasting up to 2 years. However, the general typical
    reactions found in lung-tissue were the same as those described by
    Simmers (1964). Condensates of the coal-tar fumes were highly
    carcinogenic when applied to the skin and intramuscularly in mice;
    condensates of the blown bitumens fumes were non-carcinogenic to the
    skin of mice and rabbits in similar tests.

        Petroleum residues derived from cracking were painted 3 times a
    week for a lifetime on the skin of albino mice. Depending on the
    cracking process, the residues exhibited various degrees of
    carcinogenic activity, but none were as active as a higher temperature
    generated coal-tar. Only those fractions distilled from the tar above
    370°C showed carcinogenic activity. Blending with a noncarcinogenic
    oil increased the carcinogenic activity of one bitumen, possibly
    because of better skin penetration (Smith et al., 1951).

        Kireeva (1968) painted groups of white SS-57 mice, once a week
    throughout the life span, with 40% solutions in benzene of various
    bitumens derived from Ukrainian crudes and coal-tar pitch. The
    control-group was painted with benzene only. With coal-tar pitch, skin
    tumours appeared in 88.4% of the animals; with bitumens prepared from
    cracking residues, they occurred in 9.5-18.4%, and with straight-run
    bitumens, depending on its origin, in only 0.0-4.6% of the animals.

        Benzene solutions of 8 bitumens of different geographical origin
    and 2 coal-tar pitches were applied twice weekly to the skin of Swiss
    albino mice throughout their lifetime. Benzene alone was applied to
    control animals (Wallcave et al., 1971). The polynuclear aromatic
    hydrocarbon content of the coal-tar pitches was found to be several
    orders of magnitude greater than that of the bitumens examined. Only
    one carcinoma and 5 papillomas were observed in 218 mice treated with
    bitumens, whereas over 90% of the coal-tar pitch treated animals
    developed such tumours. Again, it was suggested that the tumour
    incidence depended on the polynuclear aromatic hydrocarbon content of
    the product tested.

        Benzene solutions of the bitumen or polynuclear aromatic fractions
    of Athabasca tar sands were not mutagenic for  Salmonella typhimurium.
    This may have been a reflection of the complex interactions occurring
    with such hydrocarbon mixtures (Shahin & Fournier, 1978).

        To summarize, in animal studies, some bitumens have been shown to
    possess some carcinogenic activity, when applied to the skin, while
    inhalation studies with bitumen vapours have proved to be negative.
    The carcinogenicity of bitumens depends to a certain degree on the
    method of production (cracking, blowing) or mixing. "Cutback" with
    high aromatic oil or coal-tar facilitates skin-contact and increases
    the carcinogenicity of the mixture. The carcinogenic activity,
    however, is low in comparison with that of coal-tar. Moreover, as Siou
    (1972) in a literature study on bitumens concluded, it is difficult to
    extrapolate from these animal data to man, because the contact with
    bitumen, even in occupational exposures, is of a quite different order
    to regularly repeated skin application throughout the life span of a
    test animal.

    5.7  Effects on Man

    5.7.1  Epidemiological studies  Occupational exposure

        Henry (1947), in his analysis of 3753 cases of skin cancer, found
    only one case in which bitumen might have been involved. The man had
    worked for 23 years as a road-worker and had been exposed to coal-tar
    in the earlier years.

        The health and the causes of death of 96 workers who had worked in
    a bitumen plant since it opened, including those who had left the
    company was reviewed by Hoogendam (1962). Exposures ranged up to 40
    years. Thirty-nine workers had been exposed for more than 20 years and
    at least 15 had been exposed for more than 30 years. No significant
    differences were found in theft general health pattern and no cases of

    skin tumours were found. One man, who had worked for 40 years in this
    plant died at the age of 55 of bronchial carcinoma. It is impossible
    to determine whether there was a relation with his work in this case.
    Vital capacities and forced expiratory volume (FEV) of those still
    working did not differ from those of a control group.

        The mortality rate of refinery workers was compared with those of
    other workers in a study on 15 437 employees of an oil refinery over
    the 29-year period 1935-63. A comparison was also made with data from
    a similar group of the outside population. The incidence of lung
    cancer was no greater in the refinery operators than in the other
    groups (Baird, 1967).

        Baylor & Weaver (1968) compared the health of 462 asphalt workers
    in 25 oil refineries with that of 379 controls. Each of the asphalt
    workers had been engaged in this type of work for at least 5 years
    with an average of 15.1 years, service. No significant differences in
    health were found between the 2 groups. The authors also studied the
    medical literature of the 20 years preceding theft publication and
    were unable to find one single case of lung or skin cancer that could
    be attributed to petroleum bitumens. Furthermore, an extensive search
    for information on the health of workers was carried out with road
    construction firms (31 companies in 24 states with 11 478 man-years of
    asphalt working and 15 boards of health of the state highway
    commissions), roofing industries (3 firms with over 1100 long-term
    bitumen workers), and bitumen trucking firms (with over 5000 drivers).
    This gave no indication that bitumen constituted a health hazard or
    that there were cancers of the skin or lungs in these groups that
    could be attributed to working with bitumen. Similar indirect
    information was obtained from 6 large insurance companies. The authors
    concluded that the bitumens in current use did not present a
    significant health hazard and that the study indicated that the
    carcinogenic or other harmful properties of most commercial asphalts
    under the present commercial usage -- if present at all -- are likely
    to be of a very low order.

        Studies conducted on behalf of the API did not reveal any
    occupational health hazards for a "medium-exposure group" of petroleum
    refinery workers. This group included asphalt workers, grease, and
    lubricant workers (Tabershaw/Cooper Associates Inc. 1974/75).

        Hermann (1975) and Hettche (1963) drew similar conclusions to
    those of Baylor & Weaver (1968) in inferring that bitumens including
    blown grades, were biologically inactive and that vapours from hot mix
    plants were not carcinogenic.  General population exposure

        Measurement of emissions of polynuclear aromatic hydrocarbons from
    various industrial processes, including bitumen "blowing" and the
    manufacture of asphalt hot-road-mixture, revealed that these
    industrial processes were not major sources of benzo(alpha)pyrene
    emissions (used as an indicator for polynuclear aromatic hydrocarbons
    emission) and certainly emitted less than residential and small
    industrial coal-burning furnaces (Von Lehmden et al., 1965).

        In the literature, the possibility is mentioned that vapours
    emanating from asphalt, or dust arising from it might contribute to
    the overall incidence o f cancer of the respiratory tract (Hueper,
    1961; Berge, 1969). There are not, however, any data to substantiate
    this assumption and, in extrapolating the results of animal testing on
    bitumen-vapour inhalation, the chances of such an effect occurring
    among the general population seem quite remote. It can be presumed
    that a lot of the confusion has been generated by the former use of
    coaltar and mixed grades for this purpose, a fact which clearly has
    not always been taken into consideration by those working in the

        In the USSR, however, the use of "carcinogenic" road material
    (that is material containing benzo  (a) pyrene) as the upper layer of
    roads is forbidden in heavily populated areas. In practice, this means
    that coal-tar must not be used for this purpose and that petroleum
    bitumen should be used instead (Gorbov & Fomenko, 1962).  High (accidental) exposure

        Burrell (1957) found a very high incidence of oesophageal cancer
    in a group of Bantu confined to one location in East London (South
    Africa). The author related this to the long-term preparation and use
    of the soporific alcoholic concoction "cidiviki", which was locally
    fermented in drums still containing a ¨-inch coating of"cutback"
    bitumen. The author presumed that enough carcinogenic material could
    have leached out into the brew to have at least acted as a

        The most common accidental over-exposure in handling bitumen is
    the occurrence of burns from hot bitumen splashes. A few cases,
    however, have been described, in which a skin tumour developed within
    1-3 months of a burn caused by hot bitumen, coal-tar, or crude oil
    (Bang, 1923; Huguenin, 1925; Gunsett, 1930; Sträuli 1957). Considering
    the total number of such bums, only a very small proportion develop
    into rumours and these cases relate to combinations of such burns with
    fresh scar tissue and/or lesions of the mucous membranes. Tumours have
    been described in similar situations following heat burns by wood,
    welding electrodes, etc. (Gunsett, 1930; Sträuli, 1957). Such skin
    tumours can occur in burn scars and are often multifactorial (Emmett,

        In relation to the vast amount of bitumen that has been used for
    many decades, the reports of tumours are extremely scarce. In fact, it
    can be postulated that, though, from animal testing, it is known that
    some bitumens are weak carcinogens, there is no evidence from normal
    occupational exposure to indicate that these compounds are a
    carcinogenic hazard to the skin or the respiratory tract. This would
    also indicate that the present pattern of use of bitumens would not
    cause any hazard, whatsoever, for the general population.

        The Asphalt Institute studied emissions from the hot-mix process
    for the manufacture of paving asphalts (Puzinauskas & Corbett, 1975).
    The concentration of polynuclear aromatic hydrocarbons in the
    particulate emission was low at 340 mg/m3 and the average
    concentration of benzo(alpha)pyrene was very low at 13 ng/m3.

    5.7.2  Clinical studies

        These relate mainly to bitumen skin burns and will not be
    considered here. Other clinical data have been included in the
    description of the epidemiological data.

        The skin of fair-haired persons might be more prone to react
    adversely to repeated prolonged exposure to UV-radiation in sunlight
    in combination with bitumen exposure (Smiley, 1951; Kinnear et al.
    1954; Emmett, 1975).


    6.1  Crude Oils

        Crude oil is normally handled in a closed system from the oil
    well, via storage tanks, pipelines, and shipment by tankers to the
    refineries. Under these conditions, health hazards to, and death of
    workers involved in these operations will occur only when a serious
    breakdown or leakage occurs. Volatile components escaping at well
    heads, at pump glands, or through vents in storage tanks and ships'
    tanks may, under certain conditions, constitute a similar health
    hazard; hydrogen sulfide, if present, is the most acutely toxic
    component but detailed consideration is outside the scope of this
    review. These volatile components may also contribute to the pollution
    of the atmosphere in storage or pumping areas. To the general
    population, this is mainly a nuisance problem, because of the odour
    from the hydrogen sulfide and mercaptans involved. Crude oil pollution
    of seas and inland waterways as a result of accidents with crude oil
    tankers or pipelines may, at times, cause a major and sudden
    environmental hazard. Tank washings from tankers not using the
    "load-on-top" system are another source of pollution of the sea with
    crude oils. However, this particular aspect falls outside the scope of
    this review.

        Atmospheric concentrations of the volatile components of crude oil
    were found to be lower near marine drilling rigs than land-based rigs.
    Differences in temperature and air movement have been shown to be the
    main causes.

        The lower temperature of marine pipelines encourages
    solidification of waxy compounds of the crude oil on their inner
    surfaces. During their repair, the clothes and skin of workers may be
    contaminated by these compounds (Alekperov et al., 1974).

    6.2  Petroleum Solvents

        Though petroleum products are widely used, they do not generally
    present a health risk for the general population, as their volatility
    prevents them accumulating in the ambient air in concentrations high
    enough to cause adverse health effects. However, if improperly used in
    closed, poorly ventilated rooms, they may become a cause of accidental
    acute poisoning. Under these conditions, the lower-boiling solvents
    may also present a fire hazard.

        Cases of accidental ingestion may occur, especially in children.
    Serious and even fatal lung disease may develop when aspiration in the
    lungs occurs. Absorption from the gut, however, is generally not a
    serious health hazard.

        Substances with a strong odour may cause a nuisance, when present
    in the ambient air, even in very low concentrations. The same applies
    to the possible contamination of drinking-water through leakage of
    petroleum solvents from containers.

        Health impairment due to occupational exposure to petroleum
    solvents occurs only infrequently in normal work practice. Repeated
    skin contact may result in contact irritative dermatitis and only
    rarely in contact allergic dermatitis. Continuous day-to-day exposure
    to excessive vapour concentrations (which usually occur in poorly
    ventilated workshops) may give rise to general non-specific symptoms
    of ill-health. Some solvents, however, have a specific systemic
    effect, e.g., benzene (bone marrow depression, leukaemogenesis) and
     n-hexane (polyneuropathies). Polyneuropathies also occur in cases of
    abusive use of petroleum solvents by "sniffers" and addicts.

        Accidental exposure to excessive vapour concentration may cause
    narcosis, which can be followed very rapidly by respiratory arrest and
    death. Accidental over-exposure of the skin, especially if the solvent
    is allowed to remain in contact with the skin, may cause skin
    irritation, possibly leading to chemical burns.

        Blood dyscrasia does not occur through exposure to petroleum
    solvents that do not contain benzene. The specific long-term health
    hazards of exposure to benzene and petroleum solvents that contain a
    substantial percentage of benzene will not be discussed in this

        The high aromatic residues that are still used, occasionally, as
    solvents for specific purposes may pose a carcinogenic risk to the
    skin or on inhalation, if such contact is intensive and prolonged.

    6.3  Lubricating Base Oils, Greases, and Waxes

        This group of products is unlikely to present a health risk for
    the general population, even with gross accidental over-exposure.
    Unrestricted and indiscriminate oral or nasal administration of white
    medicinal oil can occasionally give rise to the occurrence of lipid
    pneumonia, when pre-existent disease or other conditions predispose to
    the entry of mineral oil into the respiratory tract.

        Prolonged and intensive contact of the skin with metal-working
    oils during occupational exposure results in a high incidence of skin
    disorders and relatively more cases of skin cancer have occurred in
    such occupations. Improvements in both industrial and personal hygiene
    have reduced the incidence of malignant and non-malignant diseases of
    the skin. Results from animal studies indicate that substitution of
    the oils, formerly used, by more refined products may significantly

    contribute to the prevention of skin cancer caused by exposure to oil
    under poor standards of industrial hygiene. Because chronic lung
    disease following exposure to oil mist is extremely rare and an
    increase in the incidence of pulmonary carcinoma has only been
    reported under exposure conditions where skin cancer occurs, it seems
    reasonable to assume that these occupational diseases can be prevented
    by suitable preventive measures.

    6.4  Bitumen

        The health risks associated with bitumen appear to be minimal,
    because contact is unlikely. Occupational exposure is not associated
    with an increase in cancer of the skin or the respiratory tract. The
    most significant occupational hazard is burning of the skin from
    splashes of heated bitumen.

        Certain bitumen grades, however, such as those derived from
    cracked oils, and those mixed with coal-tar or high aromatic extracts,
    may have a carcinogenic potential and, therefore, require special
    precautions in handling.


    7.1  General

        Every effort should be made not to contaminate workers, the work
    place, or the general environment with petroleum products. Proper
    design of machinery, equipment and the workshop, enclosure of
    processes, adequate ventilation, provision of protective clothing and
    adequate facilities for personal hygiene, suitable education and
    supervision, and development of safe working procedures are essential
    basic requirements; good hygienic work practices can achieve a great
    deal in protecting the worker.

        Care should be taken, when developing products, to ensure that
    levels of the most toxic components, e.g., benzene,  n-hexane, and
    polynuclear aromatic hydrocarbons are known, so that proper controls
    can be devised for the use of the products.

        Products containing such highly toxic components should, when
    possible, be avoided and alternatives sought, where exposure is
    unavoidable or is likely to occur. Products which, during use, may
    generate more and highly toxic contaminants should be identified and
    efforts made to reduce contamination. Care should be exercised when
    handling and using such products and consideration given to the need
    for renewal of products at appropriate intervals. In relation to
    metal-working, the danger of repeatedly "topping-up" machinery over
    long periods with a product, and of mixing different products in one
    machine, is emphasized.

        Where contact is unavoidable, suitable protective equipment should
    be used, although this should always be used as the last resort. Where
    skin contact is inevitable, efforts should be made to limit or avoid
    not only benzene,  n-hexane, and polynuclear aromatic hydrocarbons
    but also any additives that may have an adverse effect on the skin.
    The use of abrasives and solvents in cleansing the skin should be

        In the less developed countries, there is often a lack of
    awareness concerning the need for proper control measures when
    handling petroleum products. In these countries, the health education
    of employers and workers should be promoted with reference to the
    products. Adequate control programmes should be implemented using
    known techniques. Whenever necessary, these should be modified to fit
    the particular circumstances of the country.

        In addition, proper planning is necessary to control the disposal
    of the many types of waste oil products so that environmental
    contamination is avoided. Thought must also be given to the need to
    control the siting of housing and amenities in relation to petroleum
    refineries and petrochemical plants.

    7.2  Petroleum Solvents

        Excessive exposures to these products should be avoided. Proper
    education of manufacturers and users and appropriate labelling of
    consumer products are important. Regular control of workroom
    atmospheric concentrations of petroleum solvents is indicated,
    especially in smaller workshops.

        Petroleum solvents are, with the exception of benzene and
     n-hexane, less toxic than most other solvents and, with suitable
    precautions, can be safely used. For this reason, and because they are
    cheap, they are widely used in industry and their replacement by other
    solvents is unlikely in the foreseeable future.

    7.3  Lubricating Base Oils, Greases, and Waxes

        The only way in which members of the general population could,
    under normal circumstances, be over-exposed to any of this group of
    compounds would be in the indiscriminate use of medicinal liquid
    paraffin. Excessive use -- especially self-administered -- of this
    material, intranasally or via the oral route, by debilitated or
    dysphagic patients should be discouraged.

        The main possibilities of over-exposure occur in the occupational
    situation. Without going into detail, the following factors should be
    considered with the aim of avoiding hazardous exposures:

        (a) Avoid contact by technological means including: proper design
    of equipment, machinery, and workshop; proper design and operation of
    general and exhaust ventilation systems in places where oil mist
    generation cannot be avoided; use of base oils with the lowest content
    of polynuclear aromatic hydrocarbons that can practically be achieved
    by suitable refining processes; limiting of the concent of additives
    that have adverse effects on the skin; frequent changing of oil in
    situations where carcinogenic compounds might be generated by heat;
    avoidance of the reuse of used oils, without refining, for other
    purposes where they might cause a health hazard; education and
    instruction in all these safe-working procedures, and supervision of
    their proper execution;

        (b) Use of safe-working procedures and, where required, protective
    clothing and proper protective equipment; availability of general
    hygienic facilities including wash-basins in or near the work-place,
    shower facilities, lockers for private clothing outside the
    contaminated area; regular changing and laundering of working clothes
    and underwear; the use of suitable emollient skin creams and in some
    instances barrier creams. Abrasives and solvents should not be used
    for cleaning the skin.

        (c) Periodic medical examinations.

        These precautions have been compiled and adapted from the
    following references: Kipling (1968); UK Medical Research Council
    (1968); Cruickshank (1969); Desoille et al. (1973); BRMA (undated).
    Manufacturer can contribute by ensuring that these precautions are
    observed in their own premises and by giving the proper information
    and guidance to the consumer (see also Eckardt, 1967).

        Government actions vary from country to country depending on local
    legislation and practice. They may range from supervision and control
    of the measures taken by industry to the issue of directives or codes
    of practice. Cautionary notices can be issued (e.g., HMSO, 1979),
    which have to be displayed in the working place, as well as leaflets
    for the workers (e.g., HMSO, 1967). Diseases caused by mineral oil may
    be notifiable as occupational diseases, according to national

        Consumer education on the possible hazards of the products used
    and their safe handling can best be done by the manufacturing
    industries, when possible in cooperation with relevant Government

        Medical action in this field would consist of cooperating in the
    team supervising the industrial hygiene of the operation, in
    pre-placement examination and selection, and later in the periodic
    medical follow-up of the exposed workers.

        Various other organic liquids meet requirements for lubricating
    oils and greases. Carboxylic esters are generally used. These
    synthetic lubricants, however, are not in abundant supply, are
    expensive, and are not likely to be widely used outside their specific
    field of application. Replacement products are sometimes more
    hazardous. For instance, cutting oils may be replaced by mixtures
    containing ethanolamine that give rise, under certain conditions, to
    the formation of nitrosamines.

        When safe lubricating base oils are used there is, on the other
    hand, no reason from an occupational health point of view to use such
    alternatives, not even in places where long-term intensive skin
    contact and/or oil mist exposure might take place. In these cases,
    industrial hygiene should be improved and personal hygiene should be
    closely supervised, regardless of the product used, to avoid excess

    7.4  Bitumen

        In road-building which is the major application of bitumen,
    alternative materials such as plastics and resins are far too
    expensive for general use. Coal-tar, which was used previously,
    presents a greater environmental health hazard than bitumen. Other
    alternatives would be concrete and bricks.

        In various other applications, such as flooring, roofing,
    protective coatings, and adhesives, alternative materials are
    available, but these are not always superior in quality and/or
    competitive in price.


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    See Also:
       Toxicological Abbreviations