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

    Published under the joint sponsorship of the United Nations
    Environment Programme, the World Health Organization and the
    International Radiation Protection Association

    World Health Organization Geneva, 1979

    ISBN 92 4 154074 5

    (c) World Health Organization 1979

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         1.1. Summary
         1.2. Recommendations for further studies
              1.2.1. Measurement of ultraviolet radiation from
                      natural and artificial sources
               Measurement devices
               Monitoring of natural sources
               Monitoring of artificial sources
               Development of personal monitoring devices
               Improvement of high intensity sources
              1.2.2. Effects of UV-B, UV-A, and visible light on
                      cells and their constituents
              1.2.3. The relationship between ultraviolet radiation
                      and skin cancer
              1.2.4. Epidemiological studies of skin cancer and
                      ultraviolet radiation deficiency in man
               Non-melanoma skin cancer
               Malignant melanoma
               Identification of populations with
                                an increased risk of skin cancer
               UVR deficiency
              1.2.5. Studies of the interaction of ultraviolet radiation
                      and environmental chemicals
              1.2.6. Studies of beneficial effects
              1.2.7. Control measures and protection
               Control measures
               Sunscreen preparations
               Behavioural modifications


         2.1. Sources
              2.1.1. Solar radiation -- the biologically active UVR
               Influence of stratospheric constituents
               Influence of clouds, haze, and smog
               Amount of sea level solar ultraviolet
                                radiation in the biologically active
                                UVR spectrum
              2.1.2. Artificial sources
               Gas discharge arcs
               Fluorescent lamps
               Carbon arcs
               Quartz halogen lamps
               Oxyacetylene, oxyhydrogen, and plasma

         2.2. Detection and measurement of ultraviolet radiation
              2.2.1. Units and conversion factors
              2.2.2. Chemical and biological detectors
               Photographic plates
               Chemical methods
               Biological detectors
              2.2.3. Physical detectors
               Radiometric devices
               Photoelectric devices
              2.2.4. Measuring devices


         3.1. Introduction
              3.1.1. Absorption spectra
              3.1.2. Evaluation of administered and absorbed doses
              3.1.3. Action spectra
         3.2. The molecular basis of the effects of ultraviolet
              radiation on living matter
              3.2.1. Molecular lesions in DNA
              3.2.2. Consequences of photolesions
              3.2.3. Repair of UVR-induced lesions
               Prereplication repair
               Repair during or after replication
               SOS repair
         3.3. Bacteria and yeasts
              3.3.1. Effects on bacterial cell constituents
                      and macromolecular synthesis
              3.3.2. Sublethal effects
              3.3.3. Effects of ultraviolet radiation of wavelengths
                      longer than 280 nm
              3.3.4. Genetic factors in photosensitivity
              3.3.5. Repair of photolesions in bacteria
              3.3.6. Yeasts
         3.4. Protozoa
         3.5. Effects on mammalian cells in culture
              3.5.1. Sublethal effects
              3.5.2. Effects of UV-A
              3.5.3. Lesions produced in DNA
               Pyrimidine dimers
               DNA-protein cross-links
              3.5.4. The consequences of photolesions in mammalian cells
               Inhibition of DNA synthesis
               Chromosome aberrations and mutagenic
              3.5.5. The repair of photolesions
               Excision repair
               Repair during or after replication
               SOS repair

              3.5.6. Effects on cell-virus relationships
               Sensitivity to vital infection
               Viral transformation
               Activation of viruses
         3.6. Effects on invertebrates
              3.6.1. Effects on eggs and embryos of invertebrates
              3.6.2. Effects on insects

         3.7. Modification of the effects of ultraviolet radiation by
              chemical agents
              3.7.1. Halogenated analogues
              3.7.2. Caffeine
              3.7.3. Furocoumarins
              3.7.4. Other photosensitizing agents
              3.7.5. Protection by carotene
         3.8. Conclusions


         4.1. General aspects
         4.2. Acute reactions in skin
              4.2.1. Epidermal changes
              4.2.2. Erythema and inflammation
              4.2.3. Tanning
         4.3. Acute changes in the eye
              4.3.1. Photokeratitis and photoconjunctivitis
              4.3.2. Cataracts
         4.4. Effects of long-term exposure of skin to UVR
              4.4.1. UVR-induced mutagenesis and carcinogenesis
               Mechanism of UVR carcinogenesis
               Tumour types
              4.4.2. Species-specificity
              4.4.3. Ultraviolet radiation as an initiating agent
         4.5. Interactions between ultraviolet radiation and chemicals
              4.5.1. Chemically-enhanced photocarcinogenesis
              4.5.2. Interaction between light and chemical carcinogens
              4.5.3. UVR-induced carcinogen formation
         4.6. Physical and quantitative aspects of ultraviolet irradiation
              in animal studies
              4.6.1. Carcinogenic action spectrum
              4.6.2. Dose-response relationships
              4.6.3. Physical factors influencing UVR carcinogenesis
         4.7. The immune response to rumour induction


         5.1. Beneficial effects
         5.2. Induction of erythema in human skin
              5.2.1. Action spectra of human skin erythema

         5.3. Natural protection against erythema-inducing ultraviolet
              5.3.1. Melanin (see also section 4.2.3)
              5.3.2. Thickening of the stratum corneum
         5.4. Solar elastosis and other dermal effects of ultraviolet
              radiation (see also section 4.2)
         5.5. Ultraviolet radiation and skin cancer in man (see also
              section 4.2)
              5.5.1. Anatomical distribution of skin cancer
              5.5.2. Occupation and skin cancer
              5.5.3. Genetics and skin cancer
              5.5.4. Geographical distribution of non-melanoma skin
              5.5.5. Dose-response relationship for skin cancer (see also
                      section 4.5.2)
              5.5.6. Mortality from skin cancer
              5.5.7. Malignant melanoma
         5.6. Phototoxic and photoallergic diseases
              5.6.1. Phototoxicity
              5.6.2. Photoallergy
         5.7. Pterygium and cancer of the eye


         6.1. The significance and extent of different environmental
              sources of ultraviolet radiation and pathways
              of exposure
         6.2. Types of biological effects and their significance
              for human health
         6.3. The risk associated with combined exposure
              with other agents
         6.4. The population at risk -- geographical distribution,
              genetic influences, and occupation
         6.5. The reliability and range of known dose-effect and dose-
              response curves
              6.5.1. Dose-effect curves for acute skin erythema
              6.5.2. Averages and limits, minimal and slightly more
                      than minimal erythema doses
              6.5.3. The "erythema range" effects
              6.5.4. Dose-response curves for keratoconjunctivitis
              6.5.5. Dose-response relationship for photocarcinogenesis


         7.1. Range of exposure limits
              7.1.1. Exposure to solar ultraviolet radiation
              7.1.2. Occupational exposure to artificial
                      ultraviolet radiation
              7.1.3. Exposure of general population to artificial
                      ultraviolet radiation
              7.1.4. Measurement of natural and artificial
                      ultraviolet radiation

         7.2. Health effects of solar ultraviolet radiation
              in the general population
         7.3. UVR deficiency and its prevention
              7.3.1. Insolation and UV irradiation of built-up areas
              7.3.2. Sunbathing and air-bathing in the prevention
                      of UVR deficiency
              7.3.3. Artificial ultraviolet radiation in the prevention
                      of UVR deficiency
         7.4. Protection against ultraviolet radiation
              7.4.1. Sunscreen preparations
              7.4.2. Clothing
              7.4.3. Behavioural conformity with environment
              7.4.4. Occupational protection



        While every effort has been made to present information in the
    criteria documents as accurately as possible without unduly delaying
    their 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 J. Chavaudra, Institut Gustave Roussy, Villejuif, France

    Dr M. Faber, Finsen Laboratory, Finsen Institute, Copenhagen, Denmark
         a  (Chairman)

    Dr C. Fröhlich, World Radiation Center, Davos, Switzerland

    Dr Y. I. Prokopenko, Sysin Institute of General & Community Medicine,
         Moscow, USSR  (Vice Chairman)

    Dr Y. Skreb, Institute of Medical Research & Occupational Health,
         Zagreb, Yugoslavia

    Professor F. Stenbäck, Department of Pathology, University of Kuopio,
         Kuopio, Finland

    Professor F. Urbach, Temple University School of Medicine,
         Philadelphia, PA, USA  (Rapporteur)

    Professor M. Wassermann, Department of Occupational Health, Hadassah
         Medical School, The Hebrew University, Jerusalem, Israel

     Representatives of other organizations

    Dr R. D. Bojkov, Atmospheric Sciences Division, World Meteorological
         Organization, Geneva, Switzerland

    Mr M. Malone, Instruments & Observing Techniques Branch, Research &
         Development Department, World Meteorological Organization,
         Geneva, Switzerland


    Dr E. Komarov, Environmental Health Criteria & Standards, Division of
         Environmental Health, WHO, Geneva, Switzerland  (Secretary)

    Dr V. B. Vouk, Environmental Health Criteria & Standards, Division of
         Environmental Health, WHO, Geneva, Switzerland


    a Also representing the Committee on Non-Ionizing Radiation of the
      International Radiation Protection Association


        A WHO Task Group on Environmental Health Criteria for Ultraviolet
    Radiation met in Geneva from 30 October to 3 November 1978. Dr V.
    Vouk, Manager, Health Criteria and Standards, Division of
    Environmental Health opened the meeting on behalf of the
    Director-General. The Task Group reviewed and revised the third draft
    criteria document and made an evaluation of the health risks from
    exposure to ultraviolet radiation (UVR).

        The first draft was prepared by Professor F. Urbach of the Temple
    University School of Medicine, Philadelphia, PA, USA on the basis of
    reviews prepared by Dr Y. Skreb of the Institute of Medical Research
    and Occupational Health, Zagreb, Yugoslavia, Professor F. Stenbäck of
    the Department of Pathology, University of Kuopio, Kuopio, Finland,
    and the Sysin Institute of General and Community Medicine, USSR. The
    second and third drafts were prepared taking into account comments
    received from the national focal points and from the United Nations
    Environmental Programme (UNEP), the International Labour Organisation
    (ILO), the World Meteorological Organization (WMO), and the
    International Atomic Energy Agency (IAEA).

        The collaboration of these national institutions, international
    organizations, WHO collaborating centres, and individual experts is
    gratefully acknowledged. The Secretariat wishes to thank, in
    particular, Professor Urbach for his help in all phases of preparation
    of the document and Dr M. Faber of the Finsen Institute, Copenhagen,
    Denmark, who assisted the Secretariat in the final editing of the

        This document is based primarily on original publications listed
    in the reference section together with several recent reviews of the
    health aspects of UVR including publications by Urbach (1969),
    Fitzpatrick et al. (1974), and Forbes et al. (1978).

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


    1.1  Summary

        Exposure to ultraviolet radiation (UVR) occurs from both natural
    and artificial sources. The sun is the principal natural source. The
    known effects of UVR on man may be beneficial or detrimental,
    depending on a number of circumstances.

        Artificial UVR sources are widely used in industry and, because
    of the germicidal properties of certain portions of the UVR spectrum,
    they are also used in hospitals, biological laboratories, and schools.
    UVR is extensively used for therapeutic purposes, as in the prevention
    of vitamin D deficiency, the treatment of skin diseases, and for
    cosmetic purposes. Artificial UVR sources are available as consumer

        The migration of people between areas of different UVR exposure,
    whether for occupational or recreational reasons gives rise to
    unforseen exposures.

        UVR can be classified into UV-A, UV-B, and UV-C regions.
    Wavelengths in the UV-C region (200-280 nm) cause unpleasant, but
    usually not serious effects on the skin and eye. Although UV-C is very
    efficiently absorbed by nucleic acids, the overlying dead layers of
    skin absorb the radiation to such a degree that there is only mild
    erythema and, usually, no late sequelae, even after repeated
    exposures. Since solar UVR below 290 nm is effectively absorbed by
    stratospheric ozone, no such radiation reaches living organisms from
    natural sources.

        Most observed biological effects of UV-B radiation (280-320 nm)
    are extremely detrimental to living organisms. However, living
    organisms are usually protected from excessive solar UV-B radiation by
    feathers, fur, or pigments that absorb the radiation before it reaches
    sensitive physiological targets. Other means of protection include
    behavioural patterns and the ability to tolerate certain UV-B
    radiation injury because of molecular and other repair mechanisms.

        Much less is known about the biological effects of UV-A radiation
    (320-400 nm). It can augment the biological effects of UV-B, and doses
    of UV-A, which, alone, do not show any biological effect, can, in the
    presence of certain chemical agents, result in injury to tissues
    (phototoxicity, photoallergy, enhancement of photocarcinogenesis).

         Beneficial effects: It is now generally acknowledged that a
    long period of UVR deficiency may have a harmful effect on the human
    body. The best known manifestation of "UVR deficiency" is the
    development of vitamin D deficiency and rickets in children because of
    a disturbance in the phosphorus and calcium metabolism. The resultant

    effect on the bone-forming processes is accompanied by a sharp
    reduction in the defensive powers of the body, making it particularly
    vulnerable to many diseases. Appropriate measures to increase UV-B
    exposure by improving the architectural features of buildings
    (orientation of windows, use of UV-B transmitting window glass), the
    use of sun and sun-and-air bathing (solaria), and the development of
    artificial UVR sources and installations (photaria) have been shown to
    correct and prevent disease states due to UVR deficiency. In
    fair-skinned people, all the beneficial effects can be obtained with
    daily suberythemal doses.

         Harmful effects: These may be acute or chronic, and involve
    primarily the eyes and skin. The acute effects of UVR on the eyes
    consist of the development of photokeratitis and photoconjunctivitis,
    which are unpleasant but usually reversible and easily prevented by
    appropriate eyewear. Acute effects on the skin consist of solar
    erythema, "sunburn", which, if severe enough, may result in blistering
    and destruction of the surface of the skin with secondary infection
    and systemic effects, similar to a first or second degree heat burn.
    The skin has natural, adaptive protective mechanisms consisting of
    increased production of the skin pigment melanin, and thickening of
    the outer horny layer.

        Chronic effects on the eye consist of the development of
    pterygium and squamous cell cancer of the conjunctiva and perhaps
    cataracts. Chronic skin changes due to UVR consist of "aging" (solar
    elastosis) and the induction of premalignant changes (actinic
    keratoses) and malignant skin tumours (non-melanoma and melanoma skin
    cancers). The evidence for a causal association of UV-B radiation with
    these chronic changes, particularly with skin cancer induction, is
    reviewed in detail.

        Additional harmful effects (phototoxicity, photoallergy, and
    enhanced photocarcinogenesis) are produced by the interaction of UVR
    and a variety of environmental and medicinal chemicals. This results
    in acute and chronic skin changes caused by UVR of wavelengths which
    are not normally of an injurious nature.

        Ranges of exposure limits for solar UVR are described in
    section 7.1.

        The following criteria for occupational exposure levels in work
    places have been proposed:

        (a) for the UV spectral region of 315-400 nm, total irradiance on
    unprotected skin or eyes, based on either measurement or output data,
    should not exceed 10.0 W/m2 for periods of more than 100 seconds,
    and, for exposure times of 1000 seconds or less, the total radiant
    energy should not exceed 1.0 X 104 J/m2;

        (b) for the UV spectral region of 200-315 nm, total irradiance
    incident on unprotected skin or eyes, based on either measurement or
    output data, should not exceed 1.0 W/m2 of energy equivalent to the
    effective irradiance relative to a 270 nm monochromatic source for 8 h
    of exposure per day. (Details of the calculation and interpretation of
    "effective irradiance" are given in section 6.

        This exposure limit is applicable for acute effects only. The
    extent to which it must be changed when long-term effects are taken
    into account is unknown, because of lack of information concerning the
    dose-effect relationships in human skin carcinogenesis.

        It must be recognized that significant nonoccupational exposure
    to UVR occurs from exposure to sunlight, particularly during the
    summer months, and throughout the year in the tropics. Thus, exposure
    limits for the general population are difficult to recommend.

        The use of artificial UVR of appropriate wavelengths in
    suberythemal doses is also proposed for prophylactic purposes in
    populations living in UVR-deficient areas of the world, and for
    workers employed in workplaces without natural illumination.

        Finally, the document describes existing protection and control
    measures such as the containment of UVR sources, and methods for
    personal protection including the use of sunscreen preparations,
    clothing, transparent material for eye and skin protection, and
    behavioural modifications.

    1.2  Recommendations for Further Studies

        The following recommendations pertain to information needed for
    the adequate evaluation of health risks and the establishment of
    appropriate protective measures and guidelines.

    1.2.1  Measurement of ultraviolet radiation from natural and
           artificial sources  Measurement devices

        Instruments are needed that can integrate incident UVR from 200
    to 320 nm according to the "effectiveness action spectrum" for skin
    and eye proposed in section 6, in order to enforce the proposed
    standard for occupational exposure to UVR. Such instruments do not
    exist at present.

        The design and accuracy of instruments for measuring UV-A
    (320-400 nm) should be improved.

        Models for the evaluation of the effective absorbed dose in the
    critical cells of the skin must be developed taking spectral
    efficiency, pigmentation, skin thickness, and other relevant factors
    into consideration.  Monitoring of natural sources

        Accurate and continuous measurement of the UVR reaching the earth
    from the sun and sky (direct and global) is necessary to:

        (a) establish baseline levels;

        (b) establish the range of natural existing variation;

        (c) monitor persistent changes resulting from various causes
    (e.g., pollution); and

        (d) establish, more reliably, the relationship between the status
    of the stratospheric ozone layer and effective UVR for various
    biological systems.

        Measurements of the spectral distribution of solar UVR should be
    continued. A network of integrating UV-B meters should be established.
    Regular observations carried out in many areas of the world with
    identical instruments for long periods (a minimum of one complete
    sunspot cycle) are needed to obtain information on UVR climatology. Of
    particular importance are measurements north of latitude 55° and in
    the region of the tropics.

        An instrument capable of measuring UVR of wavelengths shorter
    than 290 nm should be developed, since such wavelengths can reach the
    earth, if the stratospheric ozone layer is compromised.  Monitoring of artificial sources

        Environmental monitoring of UVR sources is necessary to recognize
    and control direct and stray radiation. Wherever chemical substances
    are handled, the monitoring should cover the whole of the UVR
    spectrum.  Development of personal monitoring devices

        Population studies using personal monitoring devices for UV-B
    radiation are needed to determine the fraction of the daily natural UV
    dose received by persons at risk either from UVR deficiency or excess,
    or from occupational exposure. The daily amount of UVR received by
    human skin must vary greatly with occupation, behaviour, and local
    climatic and environmental conditions. Little is known about these
    factors and this seriously interferes with the interpretation of
    existing data on the relationship between UVR and the development of
    skin cancer and of chronic skin and eye damage. Thus, the development
    of personal UVR monitoring devices is of the utmost priority.  Improvement of high intensity sources

        One major problem in applying data from field measurements of UVR
    to the projection of changes in the incidence of skin cancer is the
    uncertainty of the shape of the action spectrum for skin carcino-
    genesis. Although the general direction and approximate limits of this
    action spectrum seem to parallel those for skin erythema, the fine
    structure of the carcinogenesis action spectrum is not known. The main
    reason for this is the lack of high intensity, narrow band, UV sources
    capable of irradiating relatively large areas (e.g., even the surface
    of one mouse). Improved high intensity, large-area solar simulators
    for chronic (1-2 year) animal studies are also urgently required.

    1.2.2  Effects of UV-B, UV-A, and visible light on cells and their

        Most of the information on the chemical and biological effects of
    UVR comes from experiments using UV-C (particularly 254 nm) radiation
    not normally found in sunlight reaching the earth's surface. There are
    recent studies showing direct and indirect effects on cells and
    cellular constituents of UV-B, UV-A, and visible light that differ
    considerably from those of UV-C. Thus, the chemical and biological
    effects of the wavelengths of UVR found in sunlight should be studied.
    There is much evidence that visible light can, under different
    conditions, either help cells to repair UVR-induced damage or can
    potentiate the detrimental effects of UVR. Thus, to better understand
    the effects of sunlight on man and his environment, experiments should
    be performed using natural sunlight or artificial lamps with
    well-known continuous spectra.

    1.2.3  The relationship between ultraviolet radiation and skin

        (a) A study is required of the effects of the interaction between
    UV-B and the rest of the solar spectrum in relation to DNA repair,
    malignant transformation, and skin tumour development.

        (b) Cellular genetics should be studied in relation to
    differences in UVR sensitivity, and defects in DNA repair.

        (c) Investigation is needed of the influence of change in the
    dose-rate of UV-B on skin carcinogenesis. Preliminary experiments show
    that protracting the delivery of a dose of UVR significantly increases
    skin carcinogenesis.

        (d) It is recommended that the effect of varying intervals
    between UVR exposures during carcinogenesis experiments should be
    studied in detail.

        (e) Studies are required to develop additional animal models,
    particularly for the study of the experimental induction of malignant

    1.2.4  Epidemiological studies of skin cancer melanoma and UVR
           deficiency in man  Non-melanoma skin cancer

        Since incidence data are extremely difficult to obtain
    accurately, prevalence data over a wide span of latitudes should be
    obtained first. Areas of study should be separated by at least 500 km
    north-south over a latitude span reaching beyond the most populated
    areas. The effect of altitude needs to be investigated. Data should
    include age at which the first tumour appears, sex, occupation, skin
    phenotype, and estimate of solar UV-B dose, obtained by personal
    dosimeters. It is of the utmost importance that all these studies be
    performed with a unified protocol, so that valid comparisons can be
    made. Promising areas for such studies are Australia (particularly
    Queensland), Finland, Scandinavia, South Africa, Yugoslavia, southern
    USSR, and the USA.  Malignant melanoma

        While much less common than non-melanoma skin cancer, malignant
    melanoma is a serious cancer with a survival rate similar to that of
    cancer of the breast. The relationship of malignant melanoma to UVR
    may be less obvious than that of non-melanoma skin cancer, and more
    detailed studies of the epidemiology, anatomical distribution, and
    associated factors of this severe skin cancer are urgently needed.  Identification of populations with an increased risk of skin

        Existing population studies on the prevalence or incidence of
    skin cancer suggest, very strongly, that persons with certain
    phenotypes such as fair skin, light eyes, and freckles, who burn
    easily and tan poorly, are at higher risk of developing skin cancer
    than others, and that this is a genetic trait (Celts).

        Efforts should be made to develop simple screening methods for
    the identification of the most susceptible members of the population.  UVR deficiency

        A study of the extent and distribution of the health effects of
    UVR deficiency is needed. The existing epidemiological studies in the
    USSR should be extended to other populations.

    1.2.5  Studies of the interaction of ultraviolet radiation
           and environmental chemicals

        Too little is known about the mechanisms of interaction of UVR
    and environmental chemical agents on biological systems. Many widely
    distributed natural or artificial chemicals (pesticides, halocarbons,
    etc.) can be altered by UVR, resulting in photoproducts that may be
    less or more biologically effective than the parent compound.

    Furthermore, many chemicals can be activated by UVR  in situ in
    biological systems and this activation may elicit a biological effect
    which neither the chemical nor the radiation alone exhibits

        Studies of the chemical, physical, and biological interaction of
    light and chemicals on biological systems at the subcellular,
    cellular, organ, and whole organism levels are much needed. Methods
    should also be developed to predict the extent and type of the
    photo-injury caused by such agents.

        An international registry and notification of photobiologically-
    effective agents would speed identification of such agents. This is
    particularly important for manufacturers and users of solaria for
    human use, now widely produced in various parts of the world.

    1.2.6  Studies of beneficial effects

        In the early photobiological literature, claims were made,
    supported by few data, of beneficial effects of UVR (other than
    Vitamin D production and subsequent effects on mineral metabolism). In
    recent years, scientists in the USSR have placed particular emphasis
    on studies of the primary mechanisms of beneficial UVR effects. More
    detailed comparable studies, particularly in man, under carefully
    controlled conditions, need to be carried out to determine the
    importance of such effects on man.

    1.2.7  Control measures and protection  Control measures

        Known UVR-emitting artificial sources should be clearly
    identified by appropriate hazard labels. Where possible, such sources
    should be housed in protective enclosures and equipped with
    appropriate safety devices including those necessary for eye and skin

        Appropriate information concerning the spectral composition,
    intensity, and handling of such sources should be provided. Licensing
    of high intensity sources is recommended.  Sunscreen preparations

        Existing sunscreen preparations differ widely in their
    effectiveness, cosmetic acceptability, and usefulness. Studies are
    needed to find new UVR absorbers, particularly in the UV-A region.
    Vehicles for application need to be improved to make such preparations
    resistant to wash-off and to ensure simple methods for the application
    of a sufficiently thick and even film to the skin.

        Methods for the uniform testing of sunscreens for effectiveness
    need to be developed and should be standardized and accepted on an
    international basis. Search for a systemically effective sunscreen is
    needed.  Behavioural modifications

        It is essential to educate the general population and workers
    concerning the profound importance of sunlight and the possibilities
    of either UVR deprivation or of acute and chronic UVR injury. It is
    also important to overcome the lack of respect for the biological
    effects of sunlight, simply because sunlight is ubiquitous, and the
    concept that, if something is natural, it must be totally beneficial
    and safe.


    2.1  Sources

        The UVR spectrum may be divided into three major components which
    induce significantly different biological effects: UV-A -- wavelengths
    from 400 nm to 320 nm (synonyms: long wave UVR, near UVR, black
    light); UV-B -- 320 to 280 nm (synonyms: middle UVR, "sunburn"
    radiation); UV-C -- 280 nm to 200 nm (synonyms: short wave UVR, far
    UVR, germicidal radiation). Wavelengths below 200 nm are of little
    biological significance, since radiation in this region ("vacuum UVR")
    is absorbed in very short pathlengths in air (Fig. 1).

    2.1.1  Solar radiation -- the biologically active UVR spectrum

        The sun, being essentially a very hot black body radiator, emits
    radiation within a wide range of wavelengths. The relative intensities
    of UV and visible radiation that reach the earth's surface depend, to
    a considerable extent, on attenuation by the atmosphere because of
    absorption and scattering. Below 320 nm, the intensity of UVR falls
    very rapidly because of absorption by stratospheric ozone. Virtually
    no radiation below 288 nm reaches the earth's surface. Thus, most
    known biological effects of solar radiation are confined to the
    extreme short end of the terrestrial solar spectrum and involve not
    more than about 1.5% of the total solar energy reaching the earth.

    FIGURE 1

        UVR is not only present in the direct solar beam, but also
    reaches the earth's surface as diffuse radiation, the solar UVR being
    scattered within the atmosphere. Under hazy and cloudy conditions this
    component can be very important.  Influence of stratospheric constituents

        The solar UVR flux that reaches the surface of the earth is a
    function of the solar spectral irradiance at the upper surface of the
    atmosphere and the absorption and scattering of UVR by the atmosphere.
    In the stratosphere, the spectral irradiance of the sun is mainly
    absorbed by ozone. Molecular ozone has a strong absorption band in the
    UVR centred at 250 nm and extending beyond 350 nm. The absorption
    coefficient falls off rapidly with wavelength and the attenuation of
    the incident solar flux is, therefore, a strong function of
    wavelength. In order to determine the impact on man of a change in the
    amount of ozone, these solar irradiances must be weighted with a
    suitable response function for human skin.

        The percentage increase in erythema-producing UVR is
    approximately 2 times the percentage decrease in ozone (Schulze,
    1970).  Influence of clouds, haze, and smog

        In addition to the absorption of the incident solar irradiance by
    ozone there is also molecular scattering by air and aerosols;
    reflection, scattering, and attenuation by clouds, haze, and smog near
    the ground; and reflection from the ground. The computation of the
    direct and diffuse radiation that impinges on a surface near the
    ground is well understood in theory, but difficult to carry out in
    practice, particularly if clouds, haze, and pollution are present
    (Belinsky & Andrienko, 1974; Green et al., 1975).

        The major factors affecting the amount of UVR in the 290-320 nm
    range that will reach the earth's surface are solar elevation (thus,
    season and latitude), and the type and amount of cloud cover and
    aerosols. The importance of atmospheric conditions and their
    variability from hour to hour and from day to day have been measured
    by Bener (1972) and Berger et al. (1975) (Fig. 2). Data on the effect
    of clouds, haze, and albedo have also been published by the Moscow
    State University group (Garadza, 1974).

    FIGURE 2  Amount of sea level solar ultraviolet radiation in the
             biologically active UVR spectrum

        The spectroradiometric measurements of global and sky UVR
    performed by Belinskij & Garadza (1962), Belinskij et al. (1968),
    Garadza (1965, 1967), Garadza & Nezval, (1971), Bener (1972), and
    Belinsky & Adrienko (1974) have served as the standards for all modern
    calculations, model systems, and comparisons with other measuring
    devices (Green et al., 1976). The global distribution of UVR has been
    illustrated by Schulze (1970) (Fig. 3).

    FIGURE 3

        Long-term results of actual measurements with an analogue
    integrating UVR dosimeter, having an action spectrum similar to that
    of skin erythema, are also available (Scotto et al., 1976). From these
    measurements, it is apparent that there are daily fluctuations,
    throughout the year, at each location. Weekly patterns are less
    erratic, and seasonal variations depend on the latitude. The solar UVR
    that causes skin erythema reaches a maximum intensity between 10h00
    and 14h00. About 60% of the daily dose reaches the ground between
    10h00 and 14h00, and 80% between 9h00 and 15h00 (Fig. 2). Similar
    observations over a shorter period of time, using an instrument based
    on a filtered selenium photocell, have given virtually the same
    results (Garadza, 1965).

    2.1.2  Artificial sources

        Any material heated to temperatures exceeding 2500 K begins to
    emit UVR. For practical purposes, sources emitting significant amounts
    of biologically effective UVR can be classified into confined gas
    discharge arcs, fluorescent lamps, and incandescent sources. It should
    be noted that any UVR source emitting intense radiation below 260 nm
    will produce ozone, which has to be removed to prevent any health
    hazard.  Gas discharge arcs

        The optical spectra produced by arcs depend on the nature of the
    gas molecules through which the current discharge takes place, its
    pressure, and the electrical conditions in the discharge.

        Direct gas discharge arcs are widely used for the generation of
    UVR. Generally, they differ from each other in such respects as the
    type of gas, pressure, starting mechanisms, lamp shape, reflector
    systems, electrodes, etc. (Andreev et al., 1975). As there is such a
    wide variety of these arcs, it is not possible to describe them all.
    However, the most important types are listed below.

         Low pressure mercury arcs. These vapour lamps emit several
    narrow UV bands. Most of the emitted power is of a wavelength of
    253.7 nm, which is near the maximum for germicidal effectiveness,
    hence its usefulness in the control of microorganisms.

         High pressure mercury arcs. These vapour arcs (operating at
    20-100 atmospheres, i.e., 200-1000 kPa, and usually encased in quartz
    envelopes) emit much broader and more intense bands of UVR than low
    pressure mercury arcs at wavelengths of 254, 297, 303, 313 and 365 nm.
    They are extensively used in industry in photochemical reactors and in
    printing. Other uses include phototherapy of skin diseases (Meyer &
    Seitz, 1949; Nilender & Gavanin, 1971).

         High pressure xenon arcs. These arc lamps may operate at very
    high internal pressures, and have the advantage that the spectral
    distribution of their radiant output shows a continuum similar to that
    of the sun above the stratosphere. Their output is quite constant over
    long periods of time, and they are available in a variety of
    configurations. The major problem with xenon arcs is their very high
    emission in the near infrared region (Gavrilova et al., 1975). Their
    uses are similar to those of mercury arcs.

         Flash tubes. Another form of gas discharge arc that produces
    UVR is usually referred to as the flash tube. The gas within a flash
    tube is excited and/or ionized, when a capacitor is discharged, to
    pass an avalanche of fast electrons through the gas between the
    electrodes. Depending on the gas used, i.e., xenon, krypton, argon,
    neon, etc., different optical spectra are produced.  Fluorescent lamps

        A fluorescent lamp contains an electric arc discharge source.
    UVR, generated at high efficiency by mercury vapour in an inert gas at
    low pressure, activates a coating of fluorescent material (phosphor)
    on the inner surface of a glass tube. The phosphor simply acts as a
    "transformer", converting shorter wavelength UVR into longer
    wavelength radiation, i.e., UV and/or visible light. The spectral
    characteristics, which depend on the phosphor used, vary with the gas
    pressure in the lamp, and the temperature at the coldest point in the

         "Fluorescent Sun" (FS) type UVR emitters. "Fluorescent Sun"
    type emitters contain a phosphor that emits more than half of its
    radiant output at wavelengths shorter than 340 nm. In general, the
    range of UVR emitted is from 275 to 380 nm, but the maximum is located
    at 313 nm. Thus, this light source is extremely effective in producing
    suntan, sunburn, and, at least in animals, cutaneous cancer. The
    linear configuration of fluorescent lamps has a distinct advantage for
    any application where a uniform irradiation field of considerable size
    is required. The disadvantage of these lamps is that there is very
    much less energy output per unit area compared with compact mercury or
    xenon high pressure arc sources (Sozin, 1975).

         "Black Light" (BL) type UVR emitters. The "Black Light" type
    UVR emitters are very similar in construction to the FS lamps, except
    that the phosphor used emits radiation ranging from 300 to 410 nm,
    with a maximum in the 350-365 nm region. Usually, BL lamps emit less
    than 0.1% of their total UVR in the less than 320 nm (i.e.,
    biologically most effective) region. Their primary use is for
    producing fluorescence in a variety of paints and inks. In recent
    years, such BL lamps have been used together with photoactive drugs
    such as 8-methoxypsoralen in phototherapy of skin diseases (Parrish et
    al., 1974).  Carbon arcs

        The arc is due to an electric discharge between two carbon
    electrodes in air at atmospheric pressure. The output of radiation
    from a carbon arc increases with increase in arc current and its more
    or less continuous shape depends, in part, on the type of metal added
    to the electrodes. The use of these arcs has been limited, because of
    gaseous waste products that require adequate venting, and the
    maintenance problems that result from consumable electrodes.  Quartz halogen lamps

        These are tungsten filament lamps, enclosed in a quartz envelope,
    filled with a small amount of a halogen gas, usually iodine or
    bromine. This allows operation at much higher temperatures without
    deposition of the metal on the envelope. Such lamps, which may operate
    at temperatures up to 3500 K or more, are stable and very intense.
    Their UVR output is mainly in the region above 330 nm, and their
    primary use is in illumination and as reference standard lamps.  Oxyacetylene, oxyhydrogen, and plasma torches

        Oil, coal, and gas flames normally operate below 2000 K and,
    thus, emit virtually no UVR. Oxyacetylene and oxyhydrogen flames burn
    at a much higher temperature and solids heated by these two flames may
    radiate UVR.

        Welding produces UVR in broad bands, which often appear as a
    continuous spectrum. The intensities of the various bands depend on
    many factors including the materials from which the electrodes are
    made, the discharge current, and the gases surrounding the arc. Arc
    welding is a common cause of UVR eye and skin damage.

        The plasma torch can produce temperatures of over 6000 K (the
    temperature at the surface of the sun) and intense UVR can result.
    Exposure to radiation from plasma torches can result in
    keratoconjunctivitis and sunburn, if eyes and skin are not protected.

    2.2  Detection and Measurement of Ultraviolet Radiation

        The measurement of UVR differs from that of visible radiation in
    that the eye cannot be used directly as a detecting instrument. Thus,
    other means for detection must be used, which can either be based on a
    physical principle, or on a chemical or biological reaction. The
    physical detectors are mainly used to measure instantaneous
    irradiance, whereas the chemical and biological detectors are normally
    used to determine radiant exposure (dose).a

    2.2.1  Units and conversion factors

        Table 1 describes terms frequently used in radiometric
    techniques, and Table 2 gives a simple scheme for conversion between
    commonly used irradiance units.

        In addition to these energy units, units of biological effect,
    based on interactions between UVR and living organisms, have been
    proposed. The oldest of these is the Finsen. More recently, a system
    of bactericidal units for evaluating UVR on the basis of its
    disinfectant effect and a system of erythema units for evaluating UVR
    on the basis of its beneficial effects on man have been described
    (Lazarev & Sokolov, 1971, 1974). In order to allow for intercomparison
    with other measurement units, the bactericidal and erythema quantities
    are now expressed in SI units (Sokolov, 1975, 1976).

    2.2.2  Chemical and biological detectors  Photographic plates

        The photographic plate is the usual detector in UV spectroscopy.
    The degree of blackening of the plate is a measure of radiation
    intensity. The measurement is made photometrically by means of some
    form of densitometer. Under carefully controlled conditions of
    exposure and development, this method is capable of a high degree of

        Ordinary photographic emulsions are sensitive in the region of
    280 to 500 nm.


    a Throughout the document, the term dose refers to the action
      spectrum weighted radiant exposure.  Chemical methods

        Chemicals which undergo some measurable change on exposure to UVR
    can be used for the measurement of radiant exposure. These methods are
    relatively simple, but are slow and require laborious analysis. They
    are sensitive to temperature and to small amounts of impurities. The
    most widely used detector has been the acetone-methylene blue
    reaction. A more accurate actinometer is based on the rate of
    photochemical decomposition of oxalic acid in the presence of uranyl
    acetate. A system based on the photolysis of iron (III) oxalate is
    more sensitive (Meyer & Seitz, 1949; Koller, 1965). Recently, chemical
    dosimeters with action spectra similar to that of human skin erythema
    have been reported by Zweig & Henderson (1976). Challoner et el.,
    (1976) have used change in the coloration of a plastic film for this
    purpose.  Biological detectors

        The human skin has been used as a UVR dosimeter in an indirect
    fashion (Robertson, 1975) and some work using microorganisms as a UVR
    dosimeter has been reported (Latarjet, 1977; Billen & Green, 1975).

    2.2.3  Physical detectors

        Physical detectors have been reviewed by Koller (1965) and Kiefer
    (1971).  Radiometric devices

        These radiation detectors depend for their response on the
    heating effect of radiation. The change of temperature due to heating
    can, for example, be detected with a thermopile or a resistance
    thermometer, that is a bolometer. Their spectral response is normally
    quite constant over a wide range of wavelengths. Because these sensors
    detect energy, they are not very sensitive to UVR and are mainly used
    for standardization.

        Table 1. Some basic radiometric terminology

            Term          SI         International     Definition    Comments and Synonyms
                         units          symbol

    Wavelength            nm, µm          lambda                     Nanometer = 10-9 metre (also
                                                                     called "millimicron", mµ;
                                                                     µm, micrometer, micron = 10-6

    Radiant energy        J               Qe                         1 joule = 1 watt second

    Radiant flux          W               phi, Pe         dQe         Rate of radiant energy delivery
                                                          dt         ("radiant power"). mW= 10-3W
                                                                     µW = 10-6 W

    Radiant intensity     W/sr            Ie              dPe        Describes the radiant flux emitted
                                                          d omega    by the source Into a given solid
                                                                     angle (solid angle expressed In

    Irradiance            W/m2            Ee              dPe        In photobiology, has been express
                                                          dA         in W/cm2, mW/cm2 or µW/cm3.
                                                                     Radiant flux arriving over
                                                                     a given area. Note Implied
                                                                     dependence of irradiance on the
                                                                     angle of the area being irradiated,
                                                                     relative to a beam. In a collimated,
                                                                     uniform beam, the irradiance
                                                                     Ee on a planar surface
                                                                     varies directly with cos theta, where
                                                                     theta = angle of incidence from normal
                                                                     to the surface ("dose-rate"
                                                                     "intensity", see section 2.2.1-1).

    Table 1 (contd)

            Term          SI         International     Definition    Comments and Synonyms
                         units          symbol

    Radiant exposure      J/m2            He              Ee x t     Has been expressed as J/cm2 or
                                                                     mJ/cm2. ("exposure dose",
                                                                     "dose", see section 2.2.1).


    Note: The subscript "e" serves to distinguish radiometric quantities from photometric quantities,
          which have a "v" subscript The "e" subscript is often dropped when only radiometric
          terms are used.
          t = exposure in seconds
    Table 2.  Conversion between irradiance units

                             W/m2         mW/cm2           µW/cm2

    1 W/m2           =         1            0.1             100
    1 mW/cm2         =        10            1                103
    1 µW/cm2         =         0.01        10-3               1
    1 erg/cm2 * s    =        10-3         10-4               0.1
    1 erg/m2 * s              10-7         10-8              10-5


    Similar conversions hold for radiant exposure units, if watts (W) are
    replaced by joules (J) in the table.
  Photoelectric devices

        These are detectors based on a quantum effect such as the
    production of electrons by absorbed photons. Their sensitivity varies
    inherently with the energy of the photon (the wavelength of the
    radiation). The place and width of the spectral response band depends
    on the detector material. In general, these detectors are much more
    sensitive than radiometric sensors.

        Photomultiplyers, photovoltaic cells, and some, semiconductors
    can be used for detecting UVR.

    2.2.4  Measuring devices

        In order to perform specific UVR measurements, the detector will
    normally be placed behind some wavelength selective device such as a
    bandpass filter or a monochromator.

        It is very important that particular attention is paid to the
    form of the spectral response, as this determines how the result can
    be used.

        For instance, the results from an instrument with a response
    according to the skin erythema will not be valuable for atmospheric
    research, or other biological effects, e.g., vision. This is because
    most of the detail of the spectral information is lost by integration

    over a specific action spectrum curve. On the other hand, high
    resolution data from a spectroradiometric device can be integrated
    afterwards for various uses. However, such measurements are much more
    complicated and expensive. Thus, there will always be a conflict
    between the information really needed and the amount of effort needed
    to acquire the data.

        Analogue integrating dosimeters are designed to simulate the
    action curve of a particular process, such as skin erythema
    (Robertson, 1969; Berger et al., 1975; Lazarev et al., 1975; Sivilova
    et al., 1975). Measurements with such a sensor are applicable only to
    biological responses with the same, or very similar, action spectra.


    3.1  Introduction

        All photobiological responses to UVR and visible radiation are
    dependent on the energy of the incident photons, with a maximum
    response at a fairly well-defined photon energy within a limited
    range, and a "threshold" beyond which the lower photon energies are
    very much less effective. This is mainly because of the ability of
    biologically important molecules to absorb appropriate photons, since
    without such absorption no effect is possible.

        The biological effectiveness of a beam of radiation depends on
    the photon flux and on the relative efficiency of the photon energy to
    produce a particular biological effect. When the beam contains photons
    with a range of energies, it is assumed that the overall effect is
    equal to the sum of all the individual contributions determined by the
    product of the intensity at each photon energy and its relative
    biological efficiency. The most spectacular photobiological effects,
    other than vision, involve photons of energy greater than about 3.9 eV
    (wavelength less than 320 nm). There are, however, some processes that
    operate on photons with energy between 4 and 3 eV and even less. When
    the effectiveness of a beam is to be evaluated, it is essential that
    the relative efficiency of all photon energies (or wavelengths) be
    known and allowed for, by comparing the appropriate action or response
    spectrum with the intensity spectrum of the beam.

    3.1.1  Absorption spectra

        Absorption of photons of UVR by a molecule results in the
    conversion of radiant energy into rotation-vibrational energy, and a
    change in the electronic configuration inside the molecule. In the
    ground state, most of the molecules are in a singlet state and
    absorption of light causes a transition into an excited singlet state
    from which they may pass into the excited triplet state of lower
    energy. For many molecules this metastable state is chemically
    reactive. However, the opposite is true for oxygen.

        The light-absorbing capacity of a molecule depends not only on
    the electronic configuration of the molecule but also on the
    possibility of higher energy states (Smith & Hanawalt, 1969). The
    absorption spectrum of a given substance is the quantitative
    description of its capacity for the absorption of photons in a
    particular range of electromagnetic frequencies.

        Among the components of living matter, only the unsaturated
    organic compounds should be taken into consideration, since others
    show negligible absorption (at least above 200 nm). The effects on
    water need not be dealt with, since it has practically no absorption
    above 185 nm (Jagger, 1969).

        Chromophores are the chemical groupings of a molecule that can
    absorb photons. Molecular constituents that contain conjugated double
    bonds freely absorb energy in the UV region. Benzene rings with one or
    two atoms of nitrogen show high absorption in the UV-B. Porphyrins,
    some steroids, and long-chain compounds such as carotene show good
    absorption in the UV-A.

        In the nucleic acids, the absorption takes place in the purines
    and pyrimidines which absorb at 260 nm.

        As far as proteins are concerned, tyrosine, tryptophane, and
    peptide bonds are the major chromophores. Absorption of UV photons by
    a protein is roughly equivalent to the sum of the absorption by its
    constituent amino acids. The absorption peak is usually located at
    280 nm.

    3.1.2  Evaluation of administered and absorbed doses

        While it is easy to measure the dose administered, the dose
    absorbed depends on: the composition of the medium, the constituents
    of which absorb differently in the UVR; the thickness of the medium;
    and on the heterogeneity of the cell material itself including the
    thickness of the cell layer, the distribution of the intracellular
    organelles and pigments, and the structure and configuration of the
    molecules at the time of irradiation (Jagger, 1967). As with
    microorganisms, most of the work on this subject has been done using
    the low pressure mercury arc, but more reports are now appearing in
    relation to UV-A and UV-B.

        In the UV-C, cells absorb in the nucleic-acid bland with a peak
    at 260 nm. Absorption between 270 and 290 nm with a peak at 280 nm
    corresponds to absorption by proteins (amino acids). In the UV-A and
    the UV-B, absorption varies considerably, depending on the quantity of
    absorbing intracellular molecules (porphyrins, haemoglobin,
    cytochrome, carotene, etc.) found in the natural state in certain

    3.1.3  Action spectra

        An action spectrum indicates the wavelengths that are most
    capable of producing a given effect. Comparison of an action spectrum
    with an absorption spectrum of certain constituents of an irradiated
    substance or cell often makes it possible to identify the component
    responsible for the effect obtained.

        In more complex systems, where secondary reactions enter into the
    effect measured, the identities of the absorption and action spectra
    become less definite, and the conclusions to be drawn, much less

        In bacteria for example, the curve of effectiveness of the UV
    wavelengths will peak at 265 nm and is similar to the absorption
    spectrum of nucleic acids. It may be deduced that the main target is
    DNA (Smith & Hanawalt, 1969).

    3.2  The Molecular Basis of the Effects of Ultraviolet Radiation on
         Living Matter

    3.2.1  Molecular lesions in DNA

        Deoxyribonucleic acid (DNA) is one of the most important target
    molecules for photobiological effects. DNA can be represented as a
    double-stranded helix built up of purine and pyrimidine bases, held
    together by sugar and phosphate groups. If the features of the DNA
    macromolecule and the universality of the cell structure of living
    organisms in which DNA represents the genetic heritage are considered,
    it can be anticipated that any lesion inflicted on DNA, however
    slight, may have serious repercussions. A lesion in a cell genome is
    always serious, because, in genera], the genome exists only in one
    copy in the cell concerned, whereas a lesion in a protein, even of the
    same magnitude, may remain undetected because there are many copies of
    the proteins. The latter is also true of ribonucleic acids (RNA).

        Most studies have been performed with low pressure mercury arcs
    emitting primarily UVR of 254 nm. Excellent reviews of this subject
    include those by Setlow (1968), Latarjet (1972), and Smith (1974).

        The effect of UVR is above all destructive. The most common
    changes produced in DNA are damage to the bases and to the
    polynucleotide chains. Damage to the bases may be unimolecular or
    bimolecular. Since pyrimidine bases are ten times more sensitive to
    UVR than purine bases, the only unimolecular reaction discussed will
    be the formation of pyrimidine hydrates.

        Bimolecular reactions are very numerous. They may occur between
    two bases, or between a base and another molecule. The most important
    effect is the formation of dimer compounds, particularly thymine
    dimers. Thymine dimers were demonstrated by Beukers & Berends (1960)
    in frozen solutions of irradiated pyrimidine (a special orientation of
    the bases being necessary before the dimers could be formed). The
    dimer brings about a twisting of the secondary helical structure of
    DNA and causes local denaturation. New biochemical methods have made
    it possible to detect dimers  in vivo in all types of irradiated
    cells studied. The number of dimers has been shown to be proportional
    to the dose of UVR and to vary with wavelength with a peak at 280 nm.
    While the production of dimers has been shown to be directly linked to
    the harmful effects of UVR on biological material, it is not the only
    serious lesion produced in DNA by UVR.

        Dimers are normally produced by UV-B but can also be formed after
    exposure to UV-A (Pollard, 1974) and after photosensitization
    reactions (Lamola & Yamane, 1967). Product additions to DNA bases are
    very numerous (Smith, 1974). Cross-links between DNA bases and
    proteins are generally formed after exposure to very high doses of
    UV-A (Varghese, 1973). They also occur following exposure to UV-A in
    the presence of photosensitizers such as acridine.

        Following exposure to UV-A, numerous addition products are formed
    with photosensitizing agents including the aromatic ketones,
    acetophenone, and benzophenone (Helene & Charlier, 1971), or the
    furocoumarins (Chandra, 1972). Polynucleotide chain breaks represent
    another type of lesion that may occur in DNA. RNA, the structure of
    which is similar to that of DNA, can be directly affected by UVR, but
    since the biosynthesis is a continuous process and RNA exists in
    multiple copies, very high doses of UVR are needed before such lesions
    have any serious repercussions. UVR also produces dimers in RNA (Huang
    & Gordon, 1973).

        The proteins that make up the bulk of the cell may sustain damage
    to the secondary or tertiary structures. Breaks may occur in peptide
    chains or bonds or cross-links (Smith, 1974).

    3.2.2  Consequences of photolesions

        The distortion produced in the DNA-molecule prevents it from
    carrying out its functions, i.e., transcription and replication may be
    blocked. These lesions can be recognized by repair enzymes or may act
    as a signal for other biological processes to intervene. They may
    result in cell death, genetic recombination, mutagenesis, or even

        Inhibition of DNA synthesis by UVR has long been known to occur
    (Kelner, 1953) and has been shown to be a sensitive parameter for
    evaluating the effects of UVR (Smith & Hanawalt, 1969). The restarting
    of DNA synthesis after a more or less long delay shows that
    photolesions can be repaired and these mechanisms are of greatest
    importance. Synthesis and transcription of RNA may also be blocked
    (Sauerbier, 1976).

    3.2.3  Repair of UVR-induced lesions

        The existence of several distinct repair mechanisms that operate
    in almost all cells but vary considerably in their respective
    effectiveness has been demonstrated in  in vivo studies of
    UVR-induced DNA lesions. The importance and complexity of the repair
    processes has been described in numerous reviews and in a book by
    Hanawalt & Setlow (1975).  Prereplication repair

         Photoreactivation. Photoreactivitation was the first discovered
    and most primitive mode of repair. As long ago as 1949, both Kelner
    and Dulbecco noted that certain bacteria contained a so-called
    "photoreactivating" enzyme. The enzyme has been shown to recognize the
    dimer and to bind to DNA in the dark. In a wet medium and with
    exposure to visible light or long-wave UVR (330 to 550 nm), which
    provides the energy needed for the reaction, the enzyme monomerizes
    the dimer by breaking the cyclobutane linkages, thus restoring the
    molecule to its original state. It is the only repair mechanism in
    which a primary UVR lesion can be chemically reversed and where repair
    is completed in a single enzymatic stage (Rupert, 1975). This mode of
    repair has been demonstrated in all living organisms including

         Excision repair. Unlike photoreactivation, this repair process
    does not require light. It takes place through recognition of the
    lesion by complex enzyme mechanisms. This repair process is not
    specific for UVR-induced dimers. Similar lesions caused by nitrogen
    mustard, 4-nitroquinoline, mitomycin C, nitrous acid, ionizing
    radiation etc., can be repaired by the same process.

        Following the formation of a dimer, DNA is incised at the bases
    near the dimer by a specific endonuclease. The DNA segment bearing the
    dimer is then eliminated by an exonuclease and the gap thus created is
    filled by local synthesis of DNA, the intact homologous strand serving
    as a template. The continuity of the strand is re-established by a
    ligase that welds the ends of the resynthesized portion to the
    undamaged continuous segment (Boyce & Howard-Flanders, 1964; Pettijohn
    & Hanawalt, 1964; Setlow & Carrier, 1964). This type of repair has
    been demonstrated in all living organisms including mammals.  Repair during or after replication

        This type of repair is not initiated by enzymatic recognition of
    the lesion. In this case, replication does occur but the lesion is
    ignored or bypassed. There remains a gap in the DNA on the side
    opposite to the damaged region which can be filled by a process of
    "recombination". Homologous DNA molecules with photolesions can use a
    process for the exchange of intact genetic material to weld together
    the undamaged segments and restore a normal DNA molecule (Rupp &
    Howard-Flanders, 1968).

        This mode of repair has also been observed in various types of
    cells. However the operational capacity of such repair processes is
    different from that of photoreactivation. These processes may become
    more easily saturated and, above certain UVR doses, the proportion of
    unrepaired lesions increases considerably.  SOS repair

        Since repair yields are never complete, the residual lesions may
    then cause errors such as mutations, the frequency of which seems to
    depend on the effectiveness of the repair systems. Witkin (1969) has
    analyzed the processes of error-prone repair in bacteria, which Radman
    (1975) named SOS repair.

        It occurs in phage and bacterial DNA which still contains lesions
    such as dimers. These can block the normal operation of other repair
    processes. The presence of these lesions represents an SOS signal for
    the triggering of certain repair mechanisms that are normally
    repressed. Replication is then effected by fraudulent incorporation of
    bases that cause mutations.

    3.3  Bacteria and Yeasts

        Most of the principles of molecular photobiology have been
    established as a result of work on  Escherichia coli and its numerous
    mutants, and on the specific phages that infect it. However, it must
    be remembered that these results may not, in all cases, be valid for
    mammalian cells.

    3.3.1  Effects on bacterial cell constituents and macromolecular

        Apart from chromosomes, structures containing membrane-bound DNA
    and structures containing RNA are the main targets for UVR-induced
    lesions, which are reflected in alterations in the templates needed
    for macromolecular syntheses. DNA synthesis is first blocked, at least
    for a time. The blockage is photoreversible. Changes in other
    biochemical constituents of varying importance may occur (Jacobson &
    Yatvi, 1976).

    3.3.2  Sublethal effects

        Functional alteration is shown by a slowing-down of the growth
    rate of bacteria, which may also grow abnormally without dividing into

        Survival is evaluated on the basis of counting the colonies that
    can be formed by surviving cells. This method is one of the most
    sensitive and most commonly used for evaluation of the biological
    effects of UVR at the cellular level.

    3.3.3  Effects of ultraviolet radiation of wavelengths longer
           than 280 nm

        Effects produced by UVR longer than 280 nm can be divided into
    those specific to these wavelengths and those that are similar to the

    effects of UV-C. The increase in complexity of the mechanisms that
    come into play at these wavelengths has been demonstrated by Mills et
    al., (1975) and Jagger (1976).

        A cell irradiated at 254 nm is said to tolerate 5´ times as many
    dimers as one irradiated at 365 nm. To kill  E.coli, a dose of UV-A
    one thousand times greater than that of UV-C or UV-B is required
    (Tyrell, 1973).

        A review by Jagger (1976), which emphasizes the complexity of the
    processes induced by UV wavelengths other than 254 nm, affords a
    glimpse of the difficulties that will be encountered in interpreting
    results relating to eukaryotic cells.

    3.3.4  Genetic factors in photosensitivity

        The UVR resistance or UVR sensitivity of the various bacterial
    mutants depends on the genetic make-up of the species concerned. The
    UVR doses that have to be used to produce the same effect, and the
    number of dimers, the induction and excision rate of which are
    responsible for this sensitivity, vary considerably (Hill, 1958;
    Setlow & Duggan, 1964; Lewis & Kumta, 1972). The enzymes responsible
    for the repairs of the lesions are also genetically coded as are the
    enzymes responsible for regulating the expression of the repair
    enzymes (Hanawalt & Setlow, 1975).

    3.3.5  Repair of photolesions in bacteria

        All the modes of repair described in section 3.2 are applicable
    to, and were mainly discovered in, bacteria. As long ago as 1963,
    Setlow & Setlow determined,  inter alia, the photoreactivation
    mechanisms demonstrating that monomerization was related to the
    decrease in the number of photolesions.

    3.3.6  Yeasts

        Yeasts are microorganisms but are nevertheless eukaryotic cells.
    Resnick (1969), Fabre (1971), Cox & Game (1974), and Haynes (1975),
    among others, have obtained a great variety of mutants with different
    photosensitivities. These mutants differ from the wild type with
    regard to UV lethality, mutagenesis, and recombination. Genetic
    analysis has shown that several recessive genes are involved in the
    control of these responses in a way that is already much more complex
    than that found in bacteria. Moustacchi et al. (1975) have reviewed
    the specific aspects of repair mechanisms in yeasts as a model for
    eukaryotic cell systems.

    3.4  Protozoa

        Protozoa, including the ciliata paramecium, tetrahymena, and
    blepharisma, and amoebae have proved very useful as tools for studies
    on the biological effects of UVR (Skreb et al., 1972; Whitson, 1972).

    3.5  Effects on Mammalian Cells in Culture

        An attempt has been made to apply the knowledge of the mechanisms
    of photolesion formation and repair discovered in microorganisms to a
    model more similar to the human body; namely established strains of
    mammalian cell cultures. The strains most commonly used are HeLa
    (human cells of cancerous origin), mouse L fibroblasts and Chinese
    hamster cells.

        The ability of a surviving cell to form a colony (Lee & Puck,
    1960) and the numerous parameters used in radiobiology (Elkind &
    Whitmore, 1967) have been widely used to study the effects of UVR on
    this material. Among the numerous works on this subject, reference has
    often been made to the review paper by Rauth (1970).

    3.5.1  Sublethal effects

        The most marked effects of UVR on cells are death, mutagenesis,
    and malignant transformation. Sublethal effects include various
    degrees of inhibition of growth and colony-forming ability. At low
    doses, the growth of L fibroblasts is merely slowed down. Higher
    doses, however, bring about lysis of the cells (Djordjevic & Tolmach,
    1967), although the value of lysis as a parameter is doubtful. All
    cell strains give a similar response.

        In a study of the colony-forming ability of synchronized and then
    irradiated cells, Djordjevic & Tolmach (1967) and Han & Sinclair
    (1969, 1971) found that cells were quite resistant at the beginning of
    G1 but that sensitivity began to increase at the end of G1 reaching
    a peak in the middle of the S phase of DNA synthesis. Thereafter,
    sensitivity gradually decreased. In G2, the situation varied
    according to the type of cell. However, all authors agree that peak
    sensitivity occurs from the beginning to the middle of the S phase of
    the cell cycle.

    3.5.2  Effects of UV-A

        Studies of the effects of UV-A on bacteria have made it possible
    to elucidate, at least in part, the complex phenomena that occur in
    mammalian cells. Wang et al. (1974) showed that cells can be damaged
    by UV-A or visible light (300-420 nm with a peak at 365 nm). The
    shoulder of the inactivation curve changes according to cell density,
    but the curves remain similar according to the origin of the strain.

        Evaluation of viability with trypan blue stain showed that, after
    exposure to 2 X 104 J/m2, 99% of human cells, 90% of mouse cells,
    and 50% of hamster cells were destroyed.

        The fact that survival depends on the density of the cell
    population suggests that perhaps some of the effects of UV-A are
    indirect. This is supported by the observation of Wang (1975) that the

    medium in which cells have been irradiated is toxic. Wang et al.,
    (1974) have also shown that riboflavin may cause considerable
    photosensitization of cells exposed to UV-A.

    3.5.3  Lesions produced in DNA

        The lesions produced by UVR in mammalian cellular DNA may be
    divided into two categories that are not mutually exclusive, i.e.,
    those that prevent replication processes and those that permit
    replication processes, but with considerable error.  Pyrimidine dimers

        It is thought that, as in other types of cells already mentioned,
    the formation of pyrimidine dimers results in the essential lesion
    that causes most of the effects observed. However, not all the
    observed effects can be attributed to dimers and other photoproducts
    should not be neglected.  DNA-protein cross-links

        As demonstrated some time ago (Smith & Hanawalt, 1969),
    DNA-protein cross-links are to be expected in view of the
    configuration of the DNA molecule, with its backbone folded back on
    itself and its association with chromosomal proteins.

        DNA-protein cross-links may also help to kill cells by preventing
    the switching-on of repair processes (Todd & Han, 1976).

    3.5.4  The consequences of photolesions in mammalian cells  Inhibition of DNA synthesis

        As in microorganisms, the major effect in mammalian cells is a
    more or less marked and long-lasting inhibition of DNA synthesis. The
    rate of synthesis can be estimated directly by incorporating tritiated
    thymidine into the DNA.  Chromosome aberrations and mutagenic effects

        As regards the effects of UVR on the chromosomes of mammalian
    cells, several types of lesions were described long ago including
    breaks and rearrangement. A review has been published by Rauth (1970).
    These lesions have been studied (among others) in Chinese hamster
    cells and human lymphocytes. Chromosome lesions are generally produced
    by low doses of UVR. Their production is enzyme-dependent and is
    related to repair mechanisms (Bender et al., 1973). They do not
    necessarily appear after the first division (Parrington, 1972). They
    can be photoreactivated and, therefore, are probably produced by
    pyrimidine dimers (Griggs & Bender, 1973). Rommelaere et al., (1973)
    discovered another widespread type of lesion in the form of
    sister-chromatid exchanges, the frequency of which increased greatly

    after UV irradiation. This parameter has been shown to be extremely
    sensitive (Ikushima & Wolff, 1974) and, thus, valuable in detecting
    very low doses of UVR, although it is not specific to that agent.

        UV and X-ray irradiation exert a synergistic effect on the
    frequency of chromosome breaks in human lymphocytes (Holmberg &
    Jonasson, 1974).

    3.5.5  The repair of photolesions

        Animal cells in culture also possess the ability to repair
    photolesions in DNA. While the lesions are comparable to those
    observed in bacteria, and have already been described, there are some
    differences in the repair mechanisms (Hanawalt & Setlow, 1975).  Photoreactivation

        It was believed that photoreactivation was absent from the cells
    of placental mammals. However, Sutherland (1974), using appropriate
    biochemical techniques, isolated an enzyme in human leukocytes with
    properties similar to those of the photoreactivating enzyme. In
    mammals, this enzyme is probably not expressed or is masked by other
    more effective repair mechanisms. Its presence in other tissues --
    nervous, hepatic, and renal -- which are never exposed to light,
    suggests that it may have other functions.  Excision repair

        The number of dimers formed in human cells increases linearly
    with the dose of UVR, if the cells are fixed immediately after
    irradiation (Cleaver & Trosko, 1969). After a variable lapse of time,
    cells begin to excise their dimers in the way already described
    (Cleaver et al., 1972). Edenberg & Hanawalt (1973) showed that, four
    hours after irradiation with 0.2 J/m2, about 50% of the dimers had
    been excised. The proportion varied between 30 and 90% depending on
    the type of cell.

        Repair replication had already been detected by autoradiography
    and shown to be unscheduled DNA synthesis which differed from the
    synthesis of normal replication (Rasmussen & Painter, 1964).

        Excision repair has been detected in rodents even though the
    efficiency is very low.  Repair during or after replication

        Numerous authors have shown by various biochemical methods that
    synthesis of DNA of low relative molecular mass takes place
    immediately after irradiation and that, a short time afterwards, this
    newly-formed DNA is of normal mass (Painter, 1975).

        The dimers prevent replication from being carried out
    continuously. Replication probably occurs between the dimers that have
    not yet been excised, leaving gaps in the new strands opposite each
    dimer of the parental strand (Lehmann, 1972). The mechanism by which
    replication fills the gaps has not yet been properly elucidated, nor
    has the degree to which the replication is error-free. It is probable
    that part, at least, of the repair is inaccurate as a result of errors
    of replication opposite a lesion. Depending on the degree of accuracy,
    either repair is total or a lesion persists that may lead to death,
    mutation, or carcinogenesis.  SOS repair

        As will be seen later, in mammalian cells, the repair systems of
    the host cell may play a part in repairing an irradiated virus
    developing in the cell.

    3.5.6.  Effects on cell-virus relationships  Sensitivity to vital infection

        Infection with herpes virus is enhanced in mammalian cells
    exposed to UV-A (Mills et al., 1975). Relatively low exposures
    increase infectivity by 20-30% and it remains high for several days.  Vital transformation

        UV-C increases the rate of transformation of mouse and hamster
    cells by various viruses (Lytle et al., 1970). However, it does not
    induce direct transformation in all cell species. Certain
    photosensitizing agents enhance this viral transformation (Casto,
    1973).  Activation of viruses

        Since some mammalian cells harbour viruses that normally remain
    latent, their activation or induction might transform them and endow
    them with the characteristics of cancer cells. UV-C exposure of rat or
    hamster cells, transformed by certain oncogenic viruses, can activate
    the production of virus particles (Hellman et al., 1974), whereas
    irradiation of normal cells can activate tumour viruses of the
    leukemia-leukosis type (Lytle, 1971).

        However, there is nothing to show that malignant transformation
    necessarily involves the development of an oncogenic virus.

    3.6  Effects on Invertebrates

        Since the invertebrates are extremely heterogeneous, it is very
    difficult to draw general conclusions, and the data on the response of
    certain invertebrates will be given without such conclusions.

    3.6.1  Effects on eggs and embryos of invertebrates

        Hamilton (1973) emphasized the value of invertebrate eggs for
    radiation studies. Since UVR has low penetration, only very
    transparent small eggs can be totally irradiated. The others must be
    stripped or dechorionated by physical or chemical means. The whole egg
    or part of an egg has been irradiated with UVR mainly to destroy
    certain cells, in order to watch how development proceeds in their
    absence and thus deduce the role they play. Some doses, while not
    preventing segmentation, arrest the onset of differentiation at the
    sensitive stage represented by the end of blastulation and the
    beginning of gastrulation.

        Wavelengths of 225-313 nm have caused appreciable delays in
    development. Undivided eggs have been shown to be highly sensitive to
    UVR (Hsiao, 1975). There has been very little work using UV-A.

        In conclusion, it may be said that, in general, eggs are well
    protected against the harmful effects of UVR. If they are directly
    exposed, they respond to UV irradiation by means of the mechanisms
    already described. From the time when the cells begin to
    differentiate, the quality and intensity of the photolesions and their
    repair depend on the stage of differentiation of the embryo. If it is
    not an advanced stage, regulatory mechanisms sometimes enable
    photolesions produced at an early stage, when the cells are still
    totipotential, to be eliminated naturally.

    3.6.2  Effects on insects

        Insects comprise a major part of ecosystems. UVR may act on the
    vital processes of the insects in different ways and these have been
    summarized by Hsiao (1975).

        From the large numbers of papers that have been written, a first
    conclusion is that UV-B is perceived by numerous insects. Several
    diurnal and nocturnal species show positive phototropism towards UVR.
    Most of the UV-A lamps used to trap insects have an emission spectrum
    with a peak at 360 nm corresponding to the peak sensitivity of the UV
    receptors in the insects. However, the peak differs slightly for each

        Solar UVR has been found to modify the biological clock in
    insects and other arthropods.

        Photoreactivation and other types of repair have been
    demonstrated in insects.

    3.7  Modification of the Effects of Ultraviolet Radiation by Chemical

        Numerous chemical agents increase the photochemical reactivity of
    nucleic acids. They act in various ways, by becoming incorporated in
    the nucleic acids, or by forming various complexes with them that
    increase their absorption or reactivity. They can also absorb UVR
    directly and transfer the energy to nucleic acids.

        Various physical factors may change the intensity of irradiation
    and the efficiency of the repair systems.

        The way in which irradiation is carried out, ie., whether it is
    continuous or fractionated, total or partial is also important in the
    evaluation of the final results.

    3.7.1  Halogenated analogues

        Incorporation of 5-bromouracil (5-BrU) and 5-bromodeoxyuridine
    (5-BUdR) sensitizes both viruses and cells to UVR. A very detailed
    review has been made by Hutchinson (1973).

    3.7.2  Caffeine

        Caffeine is a trimethylxanthine that acts by inhibiting the
    repair systems. At doses not themselves toxic, caffeine considerably
    increases the effects of UVR.

        The absence of any effect of caffeine on excision repair suggests
    that it acts by interfering with a post-replication system (Cleaver &
    Thomas, 1969).

    3.7.3  Furocoumarins

        Photosensitizers are becoming increasingly important among agents
    that modify the effects of UVR on biological systems.

        Furocoumarins are natural products isolated from plants.
    Important applications in therapy have led to thorough studies of
    their mode of action at the molecular level (Chandra, 1972; Pathak et
    al., 1974).

        Musajo et al., (1974) have shown,  in vitro, that furocoumarins
    exert photosensitizing effects following irradiation at wavelengths of
    320-400 nm. These effects result from the formation of certain
    addition products with DNA and particularly from the linking of the
    furocoumarin molecule with the pyrimide bases. These products may
    cause breaks in the molecule and thus prevent if from carrying out its
    functions. Oxidation of amino acids may also occur in proteins.

        The so-called 'linear' furocoumarins such as psoralen react with
    native DNA in the presence of UVR to make, monofunctional and
    bifunctional addition products. The latter cause cross-linking between
    the DNA strands. Certain so-called 'angular' furocoumarins (angelicin)
    can only give rise to monofunctional addition products.

        These addition products cause lesions that can be repaired by the
    excision repair mechanism. Monofunctional addition products seem to be
    easier to repair than bifunctional products (Chandra et al., 1976).

        Depending on their molecular structure, not all the furocoumarins
    show the same degree of photosensitization. Ben Hur & Elkind (1973)
    demonstrated that, following exposure of hamster cells to UV-A, 11% of
    the addition products were formed between the complementary strands.
    During incubation in the dark, 90% of the cross-links gradually
    disappeared from the DNA.

        These reactions have found applications in the treatment of
    certain skin diseases, particularly psoriasis.

    3.7.4  Other photosensitizing agents

        Charlier & Helene (1972) carried out an  in vitro analysis of
    the photochemical reactions of benzophenone and acetophenone with
    purine and pyrimide derivatives in aqueous solution during irradiation
    with light between 400 and 600 nm. Dimers and chain breaks were the
    essential lesions.

        The effects of light on bacteria in the presence of
    photosensitizing chemicals such as toluidine blue and acridine yellow
    were compared by Harrison (1967). The four sorts of lesions observed
    -- lack of colony-forming capacity, DNA lesions and mutations, changes
    in cell permeability, and enzyme inactivation -- were similar in both

        Rauth & Domon (1973) studied the mechanisms of photosensitization
    in animal cells in cultures with 1-cyclohexyl-3(2-morpholinyl-4-ethyl)
    carbodiimide metho- p-toluene sulfonate (CMEC), which binds
    preferentially to partially denatured regions of DNA after irradiation
    at 254 nm, thus inhibiting replication and increasing lethality.

    3.7.5  Protection by carotene

        Since the work of Cohen-Bazire & Stanier (1958), some
    investigations have established the protective role of carotene
    against the photodynamic effects of light, in very special cases.
    Since the energy level of carotenes is very low, they can accept, by
    transfer, the energy of sensitizers transformed into the triplet state
    and even the energy of oxygen transformed into the singlet state by
    exposure to light.

        Mutant strains of bacteria and fungi lacking carotenoids have
    proved much more sensitive to photodynamic effects than normal
    strains, but this effect is only valid for wavelengths shorter than
    those that carotenes absorb (Mathews & Krinsky, 1965).

    3.8  Conclusions

        Knowledge of the molecular basis for the biological effects of
    UVR has emphasized the importance of the photolesions produced in DNA
    and the effectiveness of the enzymatic stages of repair, both of which
    depend on the genetic make-up of the organism concerned.

        Studies of the sensitivity of mutants, on one hand, and of
    factors able to modify the effects of irradiation, on the other, will,
    perhaps, make it possible to strengthen repair systems and to increase
    the resistance of organisms to UVR.

        The great differences observed make it difficult to lay down
    protection standards.


    4.1  General Aspects

        The anatomical structure of the skin of vertebrate animals
    resembles that of man in many respects. The surface stratum corneum is
    important in affecting the penetration of UVR (Fig. 4), the
    thicknesses of the stratum spinosum and stratum granulosum also affect
    the relative amounts of UVR reaching the dermis. Other constituents of
    the skin, e.g., the melanocyte population, the Langerhans cells,
    vascular structures, as well as cutaneous innervation vary in amount
    and distribution from species to species, but remain basically the

    FIGURE 4

    4.2  Acute Reactions in the Skin

    4.2.1  Epidermal changes

        Histological investigations of the early effects of UV
    irradiation on animal skin show the changes that occur in the
    epidermal cells particularly well.

        Twenty-four hours after a single irradiation of skin with an
    unfiltered mercury vapour lamp at doses between four and eight times
    the minimal erythema dose, distinct signs of cell injury can be seen
    including vacuolation of the cell cytoplasm and increased or decreased
    density of the nucleus (Stenbäck, 1975a).

        One distinctive feature, observed in both man (Daniels et al.,
    1961) and experimental animals (Woodcock & Magnus, 1976) 24 hours
    after exposure, is the presence of "sunburn cells" (SBC), scattered
    diffusely throughout the superficial epidermis. These cells are
    characterized by a densely-staining, glassy, homogeneous cytoplasm and
    pyknotic nuclei. The appearance is similar to that of an individual
    cell undergoing keratinization and thus, the process is regarded as a
    form of individual cell shrinkage necrosis or dyskeratosis.

        Following these early effects, hyperplasia, induced by radiation,
    is observed (Blum et al., 1959; Stenbäck, 1975a). An increase in
    mitosis indicates the onset of hyperplasia, which begins after about
    two days.

        Quantitative measurements have been made of the following aspects
    of the effects of single doses of UVR on mouse skin (Blum et al.,
    1959): (a) incidence of mitotic figures; (b) number of epidermal cells
    per unit area; (c) epidermal thickness; (d) dermal thickness; (e) mean
    nuclear diameter; and (f) number of groups of mitotic figures. All the
    aspects measured changed in a similar fashion quantitatively following
    irradiation; they increased rapidly at first, reaching a maximum and
    then fell gradually towards normal. Soffen & Blum (1961) found a
    gradual increase in epidermal thickness reaching a maximum between 8
    and 14 days. These changes represent repair of the cell injury caused
    by UVR; at the same time, the hyperplasia protects against further UV

        For a long time, it was believed that thickening of the horny
    layer was the essential adaptive change to UV irradiation in the
    environment. The idea now prevails that melanin granules in the horny
    layer and the Malpighian layer accumulate to form a protective screen
    which is not only significant, but possibly even more important for
    light protection than the thickness of the horny layer alone.

    4.2.2  Erythema and inflammation

        Sunburn (UVR erythema) and suntanning are the visible signs of UV
    injury to the skin and the repair of such injury. UV erythema is
    evidence of an inflammatory reaction to radiation, and appears after a
    latent period of a few hours.

        Erythema caused by UVR is confined to the exposed areas and
    reflects blood vessel dilation and increased blood flow in the dermis.
    It is often assumed that the initial photochemical reaction is in the
    epidermis, where photon absorption by keratinocytes may lead to
    liberation of intracellular substances that diffuse into the papillary
    dermis to cause vasodilation. This diffusion theory is supported by
    the existence of a latent period between exposure and erythema, and by
    the fact that much of the radiant energy of the erythemogenic
    wavelength region is absorbed by the epidermis. However, there may
    also be direct injury to the vascular endothelium or to other sites in
    the dermis.

        Most studies of the mechanism of "sunburn" have used artificial
    sources of UV-B or sources in which the spectral distribution is such
    that UV-B is assumed to provide the major erythemogenic influence. In
    experimental animals, the vascular response to UVR is biphasic. A
    transient immediate vasopermeability is followed, after a latent
    period of 2-8 hours, by a delayed, prolonged, increased,
    vasopermeability and vasodilation. In some animal models, the initial
    vasopermeability is accompanied by a faint erythema, which may begin
    during exposure. This immediate effect has been attributed to
    histamine release, possibly due to a direct effect of photons on
    dermal mast cells. There is evidence that serotonin may also play some
    role. In rats and guineapigs, serotonin and histamine antagonists
    suppress the immediate phase of UVR vascular responses.  In vivo
    studies of human skin have shown the transient appearance of kinins
    within minutes of UV irradiation. Kinin was not found after the onset
    of delayed erythema.

        The mediators of the delayed phase of UVR-induced vascular
    response have been difficult to define. Antihistamines do not suppress
    the delayed erythema phase of the vascular response to UVR in
    guineapigs, rats, or man. Kinins have been stated to be either absent
    or not elevated. Delayed erythema was not suppressed by various
    inhibitors of proteases, plasminogen activitors, or kallikrein.
    Serotonin has been found in urine following exposure to UVR, but the
    significance of this finding is not clear.

        More recently, prostaglandins, a group of long-chain fatty acids
    with vasoactive properties, have been implicated as possible mediators
    of the delayed phase of erythema. Prostaglandins are produced in human
    and animal skin (prostaglandin groups E and F), intradermal injection
    of prostaglandins produces erythema (PGE mainly, PGF group are much
    less active), and furthermore the production of prostaglandins
    increases following UVR exposure. Indomethacin is a potent inhibitor

    of the conversion of arachnidonic acid to active prostaglandin, a
    reaction catalyzed by the enzyme prostaglandin synthase. Topical
    indemethacin produces a profound and prolonged blanching of
    UV-B-induced, delayed erythema in both human subjects and guineapigs.
    In man, intradermal indomethacin has been shown to consistently
    decrease erythema due to UV-B but not all areas of erythema caused by
    irradiation with UV-C; these effects appear to be due to the
    inhibition of prostaglandin synthase.

        It has been suggested that the complex reaction known as
    "sunburn" may result from the release of hydrolytic enzymes and
    possibly other substances by lysosomes within keratinocytes.

        Histochemical studies of human skin exposed to UVR were
    consistent with the theory that specific damage to lysosomal membranes
    caused partial to complete rupture and release of enzymes.

        The release of lysosomal enzymes may not only lead to damage of
    the keratinocytes but may also release enzymes, vasodilator
    substances, or subsequently formed cell-breakdown products into the
    dermis, where they may directly or indirectly lead to erythema. It has
    been suggested that the immediate erythema caused by UV irradiation
    results from disruption of lysosomes of endothelial cells with release
    of chemical mediators. The delayed erythema could then result from
    secondary diffusion of proteinases from the epidermis, following
    lysosomal rupture. It is also possible that direct photon damage to
    the lysosomes of mast cells of the dermis or endothelial cells of
    dermal blood vessels may play a role in the delayed erythema of

        Multiple chromophores may exist in skin, and irradiation probably
    leads to activation of a complicated cascade of mediators, the final
    endpoint of which is erythema. Multiple pathways may exist. It is also
    possible that photons have direct effects on blood vessels or nerves.
    UVR causes dilation of isolated exposed dermal blood vessels. Dermal
    proteins may be directly changed by radiation (Magnus, 1977).

    4.2.3  Tanning

        In addition to erythema, another consequence of exposure to UVR
    is the pigmentation of the skin generally known as "tanning". This
    becomes noticeable about 48 h after exposure and increases gradually
    for several days. Tanning is, in part, due to migration of the pigment
    melanin already present in the basal cells to the more superficial
    layers of the skin where it has a greater effect on the appearance of
    the reflected light. It is also partly due to the formation of new

        It is generally accepted that repeated irradiation with UVR
    induces increases in the population of melanocytes in the epidermis of
    man and experimental animals. With regard to the mechanism of this
    phenomenon, the following processes or possibilities have been

    considered: (a) increased division of melanocytes; (b) activation of
    pigment formation in amelanogenic melanocytes: (c) migration of dermal
    melanocytes into the epidermis; (d) various combinations of these
    processes (Quevedo et al., 1965). That division of melanocytes occurs
    has been shown in murine skin by Quevedo et al. (1963). Further,
    published reports have provided evidence in support of the occurrence
    of activation of amelogenic melanocytes in man (Mishima & Widlan,
    1967) and experimental animals (Reynolds, 1954; Quevedo & Smith, 1963;
    Miyazaki et al., 1968; Sato, 1971). However, the relative contribution
    of each process remains to be established. In a study using tritiated
    thymidine, it was demonstrated that approximately 1.1% of
    dopa-positive epidermal melanocytes were labelled in hairless mice
    receiving 9 daily exposures to UVR (Sato & Kawada, 1972). However, an
    attempt to trace the labelled melanocytes using split epidermal sheets
    was unsuccessful.

    4.3  Acute Changes in the Eye

    4.3.1  Photokeratitis and photoconjunctivitis

        Although more energetic than the visible portion of the
    electromagnetic spectrum, UVR cannot be detected by the visual
    receptors in mammals, including man, because of absorption by the
    ocular media. Thus, exposure to UVR may result in ocular damage before
    the recipient is aware of the potential danger. Many cases of
    keratitis of the cornea and cataracts of the lens have been reported
    due to exposure to UVR produced by welding arcs, high-pressure pulsed
    lamps, and the reflection of solar radiation from snow and sand.

        Extensive reviews of the literature on the biological effects of
    UVR have been compiled by Verhoeff et al. (1916) and Buchanan et al.
    (1960). Verhoeff and his colleagues included all the, then available,
    research data in their report and formulated some of the basic
    hypotheses regarding ocular damage caused by UVR. Research on
    threshold values and destructive and repair processes was summarized
    by Duke-Elder (1926). Buschke et al. (1945) stressed the destructive
    effects of UVR on the corneal epithelial cell nuclei, the loss of
    epithelial adhesion to Bowman's membrane, and the inhibiting effects
    of UVR on the healing process.

        In studies by Cogan & Kinsey (1946), a monochromator was used to
    evaluate the sensitivity of the cornea to individual spectral lines.
    Their work, which was, for the most part, carried out with one to four
    rabbits, provides the most reliable quantitative data on damaging
    threshold values of UV energy of individual wavelengths. They
    established a long wavelength limit of between 306 and 326 nm and a
    threshold of 152 J/m2 at 288 nm for the rabbit.

        Ordinary clinical photokeratitis is characterized by a period of
    latency that tends to vary inversely with the severity of exposure.
    The latent period may be as short as 30 min or as long as 24 h, but is
    usually 6-12 h. Conjunctivitis follows, often accompanied by erythema

    of facial skin and eyelids. There is a sensation of a foreign body or
    "sand" in the eyes and various degrees of photophobia, lacrimation,
    and blepharospasm. The importance of these acute symptoms lies in the
    fact that the individual is visually incapacitated for 6-24 h and that
    the ocular system, unlike the skin, does not develop tolerance to
    repeated exposure to UVR. Almost all discomfort disappears within
    48 h, and exposure rarely results in permanent damage.

        Pitts & Kay (1969) and Pitts (1970) sought to establish the
    experimental threshold for photokeratitis in rabbits and primates,
    including man. Rabbits and monkeys showed a maximum sensitivity to UVR
    at 270 nm. The radiant exposure threshold for man at 270 nm was
    50J/m2 compared with 110 J/m2 for the rabbit and 60 J/m2
    for the monkey.

        The UVR incident on the eye is absorbed in turn by the cornea,
    the aqueous humor, the lens, and the vitreous humor before reaching
    the retina. Absorption is greater in the lens than in the cornea, and
    is least in the aqueous humor. Below 300 nm, most of the UVR is
    absorbed in the cornea and aqueous humor and very little penetrates as
    far as the lens.

        As a result of observations at above-threshold intensities, it
    was felt that the reaction of the cornea to exposure to UVR wavebands
    of 220 to 250 nm was different from that to wavebands of 250 to
    310 nm. For exposures below 250 nm, signs and symptoms occurred soon after
    exposure, and symptoms always returned to normal approximately 14 h
    later. For exposure above 250 nm, symptoms did not generally occur
    until 9 to 11 h after exposure, and visual acuity remained below
    normal for 24 h after exposure. The differences observed were
    attributed to the differences in the absorption of the different
    wavebands. The shorter wavebands are absorbed in the outer corneal
    epithelial layers, which undergo rapid change, whereas the longer
    wavebands are absorbed in the deeper epithelial layers which show
    delayed changes because these cells are more viable. Thus, the lesions
    produced by shorter wavelengths are rapidly repaired while, at the
    longer wavelengths, there is a delayed and more serious response
    (Pitts & Cullen, 1977).

    4.3.2  Cataracts

        A cataract is a partial or complete loss of transparency of the
    crystalline lens or its capsule. The wavelengths that affect the lens
    appear to be in the same area as those that are most effective in
    producing erythema on human skin.

        Bachem (1956), using a filtered UVR system, concluded that
    exposure to repeated high doses of longer UVR wavelengths could cause
    cataracts through cumulative effects. He reported that the action
    spectrum for cataracts began abruptly between 293 and 297 nm, reached
    a peak near 297 nm, and fell abruptly near 313 nm. Minimal effects
    existed through the remainder of the near UVR. In both the rabbit and

    guineapig, reversible lenticular "blurring" occurred 5 to 10 days
    after exposure. With repeated excessive exposures to the 297-355 nm
    wavebands, irreversible lenticular opacities occurred after a latent
    period of between 2.5 and 15 months.

        Bachem (1956) concluded that since daylight does not contain any
    UV-C or far infrared, and since both the visible and near infrared are
    freely transmitted by the ocular media, it would appear that UV-B and
    A are responsible for cataracts.

        The chemical effects of UV-A exposure on tryptophan were studied
    by Zigman et al. (1973) using human crystalline lenses. They found
    that exposure of tryptophan to UV-A led to the formation of chromatic
    photoproducts which bound to the lens proteins, altered their colour
    and changed the solubility. Human lens material without added
    tryptophan did not show chromatic changes on exposure to UV-A, until
    48 h after exposure. Tryptophan showed an excitation wavelength at
    278 nm and a fluorescent emission at 330 nm. However, following
    exposure to UV-A, tryptophan showed an additional 360 nm excitation
    and 440 nm fluorescence similar to that found in the brunescent human
    cataract lenses. The UV irradiance for these studies was 30-50 W/m2
    at 365 nm and exposures were made for at least several hours. These
    exposure levels exceed those expected from sunlight for the same
    period of time.

        Thus, exposure of the eye to UV-A, for sufficient periods of
    time, with an irradiance comparable to the irradiance level of
    sunlight may interfere with the synthesis of lens proteins, catalyse
    insoluble lens protein, and may result in chromatic changes in the
    lens. While the basic mechanisms remain to be found, the evidence
    clearly demonstrates that both  in vitro and  in vivo exposure to
    UV-A can enhance cataractous changes in the crystalline lens.

        Recently, Pitts & Cullen (1977) have studied the effects of the
    300 nm-400 nm wavelength range on the rabbit eye  in vivo. The
    criteria used to determine corneal damage were epithelial debris,
    epithelial stippling, epithelial granules, epithelial haze, epithelial
    exfoliation, stromal haze, stromal opacities, and endothelial
    disturbances. Anterior chamber signs included flare and cells. The
    crystalline lens criteria were subcapsular opacities, capsular and
    stromal haze, stromal opacities, and increased prominence of the
    anterior suture. Criteria for the iris were the presence of the
    anterior chamber signs, changes in clarity of the iris stroma, and
    sluggish pupillary response.

        Tables 3 and 4 show data for corneal and lenticular damage in the
    290 nm-400 nm wavelength range for the rabbit. Limited data above
    300 nm for the human eye do not allow a detailed comparison; however,
    the human corneal threshold was considerably below that for either
    the rabbit or the nonhuman primate.

        Table 3.  UV threshold data for the rabbit cornea and lensa
                                                                     Threshold radiant exposure
      Wavelength        Threshold radiant exposure (J/m2)              permanent damage (J/m2)

                         corneal      lens        time to              lens       time for permanent
                        threshold   threshold    disappear           threshold     damage to appear

          295               200        7500        24 h               10 000              2 h
          300               500        1500         3 days              5000             24 h
          305               700        3000         7 days              5000             24 h
          310               550        7500         2 weeks           15 000             24 h
          315            22 500      45 000         1 week            60 000             24 h
          320            75 000    > 80 000          --                  --               --
          335           109 000   > 150 000          --                  --               --
          365         > 250 000   > 250 000          --                  --               --


    a From: Pitts & Cullen (1977).

    Table 4.  Permanent lenticular opacitiesa

     Wavelength    Radiant exposure      Appearance of    Permanenceb of
        (nm)            (J/m2)          lens opacities    lens opacities

         300             5000               24 h           permanent
         305             5000               24 h           permanent
         310           15 000               24 h           permanent
         315           60 000               24 h           permanent

    a From: Pitts & Cullen (1977).
    b Lenticular opacities present one month after exposure.

        Phototoxic psoralen derivatives have been used recently in the
    treatment of certain dermatological conditions. Such compounds caused
    UV-A-induced corneal opacities and cataracts in mice (Griffin, 1959;
    Koch, 1967).

        Research on the effects of psoralens on the production of
    cataracts in man needs to be pursued. As more and more people are
    subjected to dermatological treatment using UV photosensitizing
    compounds, the role of these compounds and their effects on the ocular
    system should be defined.

    4.4  Effects of Long-Term Exposure of Skin to UVR

        UV irradiation induces an inflammatory response and ulceration in
    both the epidermis and the dermis, the latter being infiltrated with
    leukocytes in the region of the lesions, and to a much lesser extent
    between them. These lesions ulcerate and the epidermis may disappear
    for a time in the centre. However, peripherally there is particularly
    active hyperplasia. The basal membrane (between the epidermis and
    dermis) may disappear for a time in the regions of these "open"
    lesions. Between the lesions, the infiltration of leukocytes is
    relatively slight.

        Injury to the epidermis and dermis, brought about by long-term
    exposure to UVR leads to dermal alteration, fibrosis, and elastosis,
    as well as to epidermal atrophy. However, experimental production of
    cutaneous elastotic changes in animals by artificial UV irradiation
    has only been reported rarely. Using histochemical methods, Sams et
    al. (1964) demonstrated focal dermal elastosis in mice after prolonged
    exposure to artificial UVR. UVR-induced changes in connective tissue
    were also seen in rat skin by Nakamura & Johnson (1968).

    4.4.1  UVR-induced mutagenesis and carcinogenesis  Mutagenesis

        The nature of the effects of UVR on DNA, described earlier, shows
    the importance and the specificity of the lesions in genetic material
    and focuses interest on the mutations that might result in the various
    cell types studied. The production of such mutations has best been
    demonstrated in bacteria.

        Among many others, Grossman (1968), Eisenstark (1971), and Witkin
    (1976) have proposed, analysed, and verified some complex mechanisms
    that control UVR-induced mutagenesis. It will be recalled also that,
    according to the results obtained by Radman (1975), most of the
    UVR-induced mutations would appear to be errors introduced in the DNA
    during error-prone SOS repair.

        Mammalian cells in culture have proved to be very suitable
    material for the study of UVR mutagenesis (Kao & Puck, 1969). There is
    quite good agreement between the dose of UVR and the proportion of
    mutants (Bridges & Huckle, 1970).

        Fox (1974) has shown that caffeine can reduce the rate of
    mutations induced by UVR in cultures of rodent cells by inhibiting a
    process of error-prone repair.

        Isolation and study of UVR sensitive mutants in animal cells have
    found remarkable applications in the study of various human xeroderma
    pigmentosum mutants (Cleaver, 1973). However, such mutations in
    mammalian germinal cells are not possible, because the cells are
    located below the depths of penetration of UVR.  Mechanism of UVR carcinogenesis

        In order to understand the possible mechanisms of UVR
    carcinogenesis, it has been necessary to study the formation and
    excision of pyrimidine directs, unscheduled DNA synthesis, and all the
    data valid for the range from bacteria to mammalian cells.

        It is now generally believed that UVR carcinogenesis results from
    a succession of events originating in a photolesion of the genetic

        From the numerous studies that have led to en elucidation of some
    of these mechanisms, it emerges that faulty DNA repair can increase
    the frequency of carcinogenesis in the following ways: by causing
    alterations in DNA, which also find expression in an increased
    frequency of chromosome aberrations and a rise in mutation rate; by
    increasing the rate of transformation of normal cells into cancer
    cells; and by facilitating the expression of latent oncogenic viruses
    able to trigger cancerous growth (Setlow, 1973; Trosko & Chu, 1973).

        Errors induced by DNA repair during the initiation phase of
    carcinogenesis seem to be the most likely mechanism leading to UVR
    cancers.  Tumour types

         Epidermal tumours. The first visible step in UVR-induced
    epidermal tumour formation in animal skin consists of cell
    proliferation, i.e., an increase in the number of squamous cells and
    cell layers, which gradually become papillomatous in character
    (Stenbäck, 1978). This is accompanied by an increase in cellular
    atypia, nuclear enlargement, hyperchromatism, indentation, and
    prominence of nucleoli. This basically proliferative response is
    frequently replaced by a dysplastic progression showing a solar
    keratosis-like pattern with cellular pleomorphism, occasionally with
    pseudo-epitheliomatous hyperplasia-like features, which ultimately
    invade the dermis. The tumours first seen are acanthomatous papillomas
    (trichoepitheliomas), with a predominantly epithelial component or
    fibropapillomas in which the tumour is composed of a fibrous stroma
    covered by squamous epithelium.

        The malignant tumours that ultimately develop are squamous cell
    carcinomas of different types including: solid keratin containing
    tumours; moderately differentiated, individually keratinizing tumours
    with distinct intercellular bridges; and less-differentiated,
    non-keratinizing spindle cell tumours, in which ultrastructural
    analysis reveals squamous cell patterns.

        Keratoacanthomas, i.e., proliferating epithelium on a cup-shaped
    base, are relatively more frequent in animals of different species
    receiving large doses of UVR than in animals treated with chemical

        Epidermal tumours are easily induced by different agents in mouse
    skin (Stenbäck, 1969). Winkelman et al. (1960) reported the production
    of squamous cell carcinomas on the backs of hairless mice exposed to
    UVR. Further studies established that carcinomas could be induced in
    this animal almost to the exclusion of sarcoma formation (Epstein &
    Epstein, 1963). In early studies, epithelial tumours were reported in
    both rats and mice (Findlay, 1930; Herlitz et al., 1930; Putschar &
    Holz, 1930), but in later studies the deeper lying dermal tumour
    response to UVR predominated. No mention of skin sarcomas was made,
    however, in the studies of Beard et al. (1936) on albino rats in which
    12 animals exhibited 9 carcinomas of the external ear, 6 sarcomas of
    the eye, and 1 carcinoma of the skin of the nose.

        The difference in the distribution of tumour types, with
    sarcomatous growth predominating in haired mice and carcinomas in man
    (Urbach, 1969) may, in part, be explained by the difference in
    penetration of UVR, a greater amount reaching the dermis in mice
    (Kirby-Smith et al., 1942; Everett et al., 1966).

         Dermal tumours. Another type of neoplastic progression seen in
    mice, particularly after intensive treatment with large doses of UVR
    over a short time period, consists of ulceration, scarring, and the
    subsequent formation of dermal tumours. These tumours begin as
    aggregates of regularly built, elongated cells with small monomorphic
    nuclei. Epithelial proliferation is occasionally observed as a
    secondary phenomenon. The tumours rarely extend grossly through the
    surface. In the early stages, they appear to be papillomas, although
    they consist entirely of fibroblastic cells. Some tumours are
    remarkably acellular, with a prominent fibrillary pattern. The tumours
    are composed of large, polymorphic cells with prominent nuclei.
    Ultrastructural analysis shows the predominant cellular components --
    a dark cell type, with hyperchromatic nuclei and scanty cytoplasm, and
    a light cell type, with large nuclei and abundant cytoplasmic
    ribosomes (Stenbäck, 1975a). The same cell types are also seen in
    malignant tumours, in which the cellular polymorphism frequently is
    considerable, with nuclear atypism and enlargement, numerous nucleoli
    and a generally disorganized arrangement. Sarcoma induction is partly
    species-specific, as these tumours were not seen in UV-irradiated
    Syrian golden hamsters (Stenbäck, 1975b) nor were they seen in
    hairless mice (Epstein & Epstein, 1963) or guineapigs, susceptible to
    chemical sarcoma induction (Stenbäck, 1969, 1975b).

        An infrequent neoplastic alteration in several animal species is
    the vascular tumour (Stenbäck, 1975b). This begins as a proliferation
    of dilated vascular spaces with regular endothelial lining. Rarely,
    the endothelium proliferates to the point of forming angiosarcomas, or
    invasive tumours composed of large, atypical cells arranged in a
    nodular pattern.

        The role of the dermis in epidermal rumour formation has been
    emphasized by numerous investigators (Orr, 1938; Mackie & McGovern,
    1958). A proliferation of elastic tissue was induced experimentally in
    mice, by Sams et al. (1964), through repeated exposure to UVR.
    Similarly, Magnus & Johnson (1965) stimulated formation of elastotic
    tissue, following early destruction of elastic fibres, with radiation
    of 300 nm from a monochromatic source. Nakamura & Johnson (1968)
    reported that dermal elastic tissue proliferation occurred in albino
    rats after chronic irradiation with UVR, only after discontinuation of
    the exposure. It was postulated by Johnson et al. (1968) that this
    change was the result of photochemically-induced alterations in
    fibroblast function, rather than the degradation of normal elastic
    fibres. In support of this concept, Epstein et al. (1969) noted that
    unscheduled DNA synthesis occurred in connective tissue cells of the
    upper dermis within minutes of exposure to UVR shorter than 320 nm,
    demonstrating a direct effect of UVR on dermal fibroblasts.

        Because of its frequent association with skin cancer formation,
    actinic elastosis has been considered to play an important role in
    tumour development. However, Sams and his co-workers (1964) and Graham
    & Helwig (1965) demonstrated that actinic elastosis was not essential
    for the development of epidermal malignancies. Furthermore, the

    experimental production of elastosis in animals has not been
    associated with cancer formation, nor has UVR-induced experimental
    cancer depended on the presence of this change (Epstein & Epstein,

        Adnexal tumour formation is not as common in UVR-treated animals
    (Stenbäck, 1975) as in, for example, carcinogen-treated rats
    (Zackheim, 1964; Stenbäck, 1969). Hyperplasia and cystic
    disorganization of hair follicle walls is very common, but rarely
    progresses to grossly visible neoplasia. Trichoepitheliomas with
    barely visible follicular arrangements are rarely seen. Even more
    uncommon are hamartomatous tumours, hair follicle-derived
    trichofolliculomas, and sebaceous gland tumours. Sebaceous gland
    epitheliomas and carcinomas are even rarer. In a study in 1930,
    Putschar & Holtz reported only a very small number of basal cell
    carcinomas in rats.

         Pigmented tumours. Studies on the induction of pigmented
    tumours with UVR have been less successful. Benign, dermal melanocytic
    lesions, or blue nevi, have been observed in hairless mice exposed to
    UVR (Epstein et al., 1967). They were grossly seen as papules, 2-20 mm
    in diameter, histologically composed of tightly arranged, heavily
    pigment-laden polyhedral cells. Subcutaneous accumulation of pigmented
    cells has also been seen in pigmented animal strains, as well as in
    the skin of the Syrian golden hamster (Stenbäck, 1976). Such tumours
    were possibly spontaneous, as the incidence was very low -- only
    around 4% -- and unrelated to treatment. They were composed of
    polyhedral or spindle-like cells arranged in a whorl-like pattern
    beginning as hyperplasia of perifollicular melanocytes, before
    spreading both laterally and deeply in the dermis. These tumours do
    not show junctional activity; they do not metastasize and rarely kill
    the host.

        Melanomas, the type of greatest interest from an epidemiological
    standpoint, are rarely seen in animals. Benign melanocytomas are
    easily induced by treatment with chemical carcinogens as shown by
    Shubik et al. (1960) and Rappaport et al. (1961). Fortner et al.
    (1961) reported spontaneous melanomas in hamsters, similar to those in
    man. However, the sensitivity of these animals to UVR is not known.
    The effect of pigment, in general, in animal models has received
    little attention. Freeman & Knox (1964a) induced melanocytoma in 67%
    of a pigmented strain of rats. The tumours had an average latency
    period of 193 days. In albino rats there was an 8% tumour incidence
    with a 283-day latency period.

    4.4.2  Species-specificity

        Three specific factors -- pigment, hair, and thickness of the
    stratum corneum -- have been found to alter susceptibility to tumour
    induction. It was found that pigmented mice required significantly
    more radiation to induce tumours than albino animals. Hair offered
    even greater protection (Blum et al., 1959), and thus the hairless rat

    appeared to be a likely subject for tumour induction studies. However,
    the results of Hueper's (1941) extensive studies indicated that this
    animal was, in fact, quite resistant to UV penetration because of its
    thick stratum corneum. Since pigment, hair, and the stratum corneum
    were limiting factors, the ears of albino mice and rats became the
    traditional test sites for experimental production of cancer by UV
    irradiation. A remarkable amount of quantitative data has been
    accumulated using this system. The usual tumour produced in this
    tissue was a sarcoma (Roffo, 1934; Grady et al., 1943b). Thus, the
    albino ear model could not be used for evaluating qualitative changes
    associated with epidermal carcinogenesis, which is the primary process
    induced by UVR in human skin.

        Winkelman and his co-workers (1960) reported the production of
    squamous cell carcinomas on the backs of hairless mice exposed to UVR.
    Further studies established that carcinomas could be induced in this
    animal almost to the exclusion of sarcomas (Epstein & Epstein, 1963;
    Epstein, 1965). In addition, UVR-induced pigmented tumours were
    reported in pigmented hairless mice (Epstein et al., 1967). Thus, the
    hairless mouse has provided a model for both the qualitative and
    quantitative examination of the carcinogenicity of UVR.

        Though penetration of UVR appears to be of obvious importance,
    other factors also influence the type of growth induced by UVR. Grady
    et al. (1943 a) found that the size of individual doses did not have
    any effect on the carcinoma/sarcoma ratio in the albino, hairy mouse
    but that reduced intervals between exposures increased the number of
    epidermal carcinomas. These findings suggest that various tissues
    respond differently to the carcinogenic effects of UVR (Stenbäck,
    1975a). In part, this may be associated with differences in
    penetration of various wavelengths of UVR. Furthermore, there are
    great species differences in the repair capability of cells.

    4.4.3  Ultraviolet radiation as an initiating agent

        The two-stage concept for skin tumour formation proposed by
    Berenblum & Shubik (1949), supposed formation of dormant tumour cells
    by a single application of a carcinogen. These latent tumour cells
    were provoked by the subsequent application of a promoter to form
    visible tumours. In his studies on the induction of skin cancer by
    exposure to UVR, Blum (1969) indicated that the process was continuous
    beginning with the first exposure and progressing to ultimate tumour
    formation. Blum's conclusions were based on experiments in which he
    (Blum et al., 1943) and Rusch et al. (1941) could not produce tumours,
    unless exposures were carried out over a minimum of 2 ´ months,
    regardless of the amount of energy used. Blum's experiments suggested
    that, with shorter exposure periods, tumour formation was not
    accelerated enough to become visible within the lifetime of the
    experimental animal. Epstein & Roth (1968), using a single exposure to
    UVR as an initiatior and treatment with croton oil as a promotor,
    concluded that croton oil stimulated rumour formation, the
    characteristics of which were established by initial exposure to UVR.

    The results of these studies were significantly different from those
    encountered when a chemical carcinogen was used as the initiator
    (Stenbäck, 1969).

    4.5  Interactions between Ultraviolet Radiation and Chemicals

    4.5.1  Chemically-enhanced photocarcinogenesis

        An equally significant problem concerns photo-induced
    carcinogenesis following the application to the skin of agents which
    are phototoxic, but not in themselves carcinogenic.

        A portion of the sunlight spectrum is carcinogenic, even in the
    absence of an exogenous photosensitizer. At the current rate of
    introduction of new compounds into the environment, it has become
    increasingly important to determine whether a readily demonstrable
    property, such as phototoxicity, can be used to predict compounds or
    treatment regimes that could enhance photocarcinogenesis.

        Concepts of chemical interaction with UVR-photocarcinogenesis are
    of recent origin. Blum (1969) and Emmett (1973) reviewed a number of
    reports dealing with the influence of phototoxic substances on
    photocarcinogenesis. The results frequently appeared to be in
    disagreement, a situation possibly reflecting differences in
    technique, including solvent, routes of administration, light sources,
    criteria for tumour recognition, and in statistical evaluation (Blum,
    1969). In addition, characteristics of some compounds (toxicity,
    carcinogencity, instability) rendered their interactions with light
    complex, and their analysis difficult.

        The relative enhancing effects on photocarcinogenesis of two
    widely recognized photoactive compounds 8-methoxypsoralen, (8-MOP) and
    anthracene were studied by Forbes et al. (1976). Both compounds were
    phototoxic, but only the 8-MOP solutions markedly enhanced
    photocarcinogenesis. Thus, the ability of a chemical to induce
    phototoxicity is not always sufficient to augment

    4.5.2  Interaction between light and chemical carcinogens

        The fact that UVR can alter several phenanthrene carcinogens
    photochemically has been known for some time. The studies of Davies et
    al. (1972 a, b) showed that the carcinogenicity of 7,12
    dimethylbenz(a)anthracene (DMBA) was reduced by light according to the
    demonstrable photochemical lability of the compound. There was also
    evidence that an additional time-dependent factor could influence this
    effect. Thus, it appears that, at least in the case of DMBA-treated
    animals, light may contribute in two opposing ways:  (a) by
    degradation of the carcinogen to non-carcinogenic products and  (b) 
    by stimulating a phototoxic response that appears to coincide with a
    relatively increased tumour yield.

        Depending on the wavelengths of the UVR used, carcinogens can be
    photodegraded to a less carcinogenic compound, or can induce
    phototoxicity which may augment carcinogenesis or cause such a severe
    local phototoxic reaction that the epithelial skin cells are nearly
    all destroyed. Thus, either enhancement or inhibition of skin
    carcinogenesis may occur, depending upon the carcinogen and the
    wavelength of the light source used.

    4.5.3  UVR-induced carcinogen formation

        The photochemical conversion of sterols to carcinogenic
    substances has been proposed as a potential explanation for the
    cancer-causing effects of light upon skin (Black & Douglas, 1973). It
    has recently been demonstrated,  in vitro, that one such compound,
    cholesterol-5a-oxide, which possesses carcinogenic properties
    (Bishoff, 1969), is formed in human skin exposed to UVR (Black & Lo,

    4.6  Physical and Quantitative Aspects of Ultraviolet Irradiation in
         Animal Studies

    4.6.1  Carcinogenic action spectrum

        Determination of the effective wavelengths or "action spectrum"
    is one of the primary objectives in the study of photobiological
    responses. However, data are not available for the action spectrum of
    UVR-induced cancer formation. The paucity of this information for one
    of the most extensively studied photobiological reactions is due to a
    number of factors, including the large number of potential
    wavelengths, the considerable number of animals necessary and the
    length of time (a matter of many months or years) required for
    exposure to each wavelength, the difficulties in immobilizing
    experimental animals, and the need for an especially good
    monochromator with practically no stray light contamination. Though
    the complete curve of the carcinogenic spectrum is not known, certain
    aspects have been determined by less sophisticated methods. Roffo
    (1934) reported that windowglass filtration eliminated the
    carcinogenic effects of sunlight on white rats. Thus the offending
    rays of the sun would be found approximately between 290-320 nm. A
    number of investigators using mercury arc and fluorescent sun lamps
    with filters have confirmed that, under their experimental conditions,
    320 nm represented the longer wavelength limit for cancer formation
    (Griffin et al., 1955; Blum, 1969). Furthermore, carcinogenic
    responses have been produced by radiation as short at 230.2 nm (Roffo,
    1934) and skin cancer has long been known to be induced by UV-C and
    UV-B. Thus the action spectrum appears to include wavelengths between
    230 and 320 nm but wavelengths between 290 and 320 nm have been shown
    to have significantly greater carcinogenic effects than UVR shorter
    than 260 nm (Rusch et al., 1941; Blum, 1943; Blum & Lippincott, 1943;
    Kelner & Taft, 1956; Tung et al., 1971).

        Freeman (1975) performed a series of experiments to provide more
    specific comparative data by testing the hypothesis that the action
    spectrum for carcinogenesis parallelled that for erythema. In these
    studies, squamous cell carcinomas developed at approximately the same
    rate and frequency, when UVR exposure was proportional to that for
    erythema, with a decreasing potency from 300 to 320 nm. No tumours
    occurred in mice exposed to 290 nm. These cancer-producing wavelengths
    are also responsible for the normal phototoxic sunburn reaction.
    Longer UV and visible light are neither erythema-producing nor
    carcinogenic under ordinary conditions.

        It cannot be assumed that the action spectra for human skin
    erythema and mouse skin photocarcinogenesis are, similar, unless a
    common chromophore or action mechanism is involved. Setlow (1974)
    proposed that the common denominator was the action spectrum for
    affecting DNA. Making some allowance for the skin transmission of UVR,
    he showed that the shapes of action spectra for DNA, erythema, and
    possibly skin cancer production were similar and could be made to

    4.6.2  Dose-response relationships

        The second law of photochemistry (the law of reciprocity of
    Bunsen & Roscoe) states that photochemical action depends only on the
    product of the light intensity and the duration of exposure. This law,
    however, holds only for primary photochemical action, and cannot be
    applied to secondary reactions. Since the biological endpoints that
    can be observed, such as erythema, pigmentation, skin cancer
    production, etc., are certainly indirect effects, and since we still
    know little about the primary photochemical reactions that underlie
    them, it is not surprising that "reciprocity"' holds only for some of
    the effects studied.

        In the first quantitative photocarcinogenesis experiments ever
    performed, Blum (1969) found that, within relatively narrow limits
    (approximate factor of 5), differences in dose, intensity, or interval
    between doses did not alter the shape or slope of tumour incidence
    curves, but only their positions on the log-time axis. Blum, however,
    was careful to point out that this was only true, as long as the
    experimental conditions remained the same until the time the tumours

        With the accumulated data, he surmised that UVR-induced cancer
    formation was a continuous process that began with the initial
    exposure and that the appearance of tumours within the lifetime of the
    animal depended on sufficient acceleration of the growth process.

        In the majority of studies on photocarcinogenesis, fixed doses of
    UVR have been given at a fixed dose rate, and the interval between
    doses altered, but in increments of at least 24 hours. Such
    experiments, while very valuable, are far removed from the conditions
    found in nature under which human skin is exposed. Man is exposed to a

    relatively low UVR flux that varies with time of day, season, and
    environmental conditions, such as cloud cover, and also during the
    exposure period.

        Two recent animal experiments have shown that both varying the
    UVR dose increment and varying the dose-rate while the daily dose
    remains constant, affects UVR-induced skin carcinogenesis.

        In the first experiment, groups of hairless mice were exposed to
    doses of UVR from a bank of "Fluorescent Sun" (FS) lamps known to
    produce skin cancer in these animals. Equal doses of UVR were
    delivered in periods of 5 minutes, 50 minutes, or 500 minutes. Thus,
    while the doses (given 5 times weekly) were the same, the flux varied
    by a factor of 10 or 100. Striking differences in both tumour
    development time and tumour yield were noted. The animals given the
    total UVR dose in 5 minutes developed tumours later and in smaller
    numbers than those given the same total dose in 50 or 500 minutes
    (Forbes, personal communication). Thus, protracting the UVR dose over
    longer time periods resulted in a striking increase in the
    carcinogenic effects of the radiation.

        In another experiment, mice were exposed to UVR doses per day
    differing by a factor of two. As Blum had found previously, the lower
    daily dose resulted in the delayed onset of first tumours without
    significantly changing the shape of the response curve (Forbes, 1978).

    4.6.3  Physical factors influencing UVR carcinogenesis

        Although the tumour-promoting properties of such physical factors
    as freezing, scalding, and wounding have been described for chemical
    carcinogenesis systems, little information is available about the
    effects of these factors on UVR-induced cancer formation. Bain & Rusch
    (1943) reported that increasing the temperature to 35-38°C accelerated
    the tumour growth rate. The stimulating effects of heat on UVR
    carcinogenesis were confirmed by Freeman & Knox (1964b). Heat also
    enhanced the acute injury response to UVR.

        Temperature does not affect the photochemical reactions that
    follow UV irradiation, but it does affect many of the biochemical
    reactions that follow the initial photochemical change (Blum, 1941,
    1969). Although it is known that heat adversely affects
    photosensitivity (Lipson & Baldes, 1960), and other phenomena of light
    injury (Bovie & Klein, 1919; Hill & Eidenow, 1923), and that heat
    alters the effects of X-ray (Carlson & Jackson, 1959), the influence
    of heat on burns produced by sunlight or UVR has rarely been
    considered (Freeman & Knox, 1964b).

        Other studies have shown that high winds and high humidity
    significantly increase tumour incidence (Zilov, 1971; Owens et al.,

    4.7  The Immune Response to Tumour Induction

        A number of studies have shown that the immune status of the host
    and tumour induction are potentially interactive processes. Chemical
    carcinogens cause alterations of the host immune-response, the type
    and extent of which depend on the rumour-inducing agent (Curtis,
    1975). UVR also profoundly affects immunological reactivity,
    particularly the immune response to skin tumours induced by UVR.
    Studies leading to this conclusion were prompted by an observation by
    Kripke (1974) that tumours induced by UVR in C3Hf mice were highly
    antigenic and are usually immunologically rejected when transplanted
    to normal, nonirradiated syngeneic recipients. This raised the
    question as to why these tumours were able to grow progressively in
    their primary host without succumbing to immunological rejection. In
    an extensive series of experiments, Kripke & Fisher (1976) found that
    pretreatment of mice with UVR for periods of time too short to induce
    skin tumours made them unable to reject transplants of UVR-induced
    tumours, even though such transplants were immunologically rejected by
    unexposed animals. This indicates that UVR-exposed mice are
    systemically altered in a way that prevents immunological rejection of
    highly antigenic UVR-induced tumours.

        Similarly, inability of unexposed secondary hosts to reject
    UVR-induced tumours after transfer of lymphoid cells from UVR-treated
    mice has been established, and demonstrates the immunological nature
    of the systemic alteration in the UVR-treated mice (Fisher & Kripke,
    1977). Furthermore, the failure of lymphoid cells from UVR-exposed
    mice to react against UVR-induced tumours is due to the presence of
    suppresser T lymphocytes in the lymphoid organs of UVR-treated
    animals. In spite of their inability to reject highly antigenic
    UVR-induced tumours, UVR-exposed mice respond normally to most other
    antigens (Kripke, et al., 1977; Norbury et al., 1977). The one
    exception is that UVR-treated mice have a transient defect in antigen
    processing in the skin, which is reflected in their inability to
    develop contact hypersensitivity reactions (Jessup et al., 1978).

        The finding that a selective immunological defect precedes the
    appearance of UVR-induced primary tumours suggests that the immune
    system might control early UVR-induced skin cancers and that tumours
    ultimately appear because of this interference by UVR with host
    defence mechanisms.

        The carcinogenic action of polycyclic hydrocarbons has been
    associated with their immunosuppressive action (Stenbäck, 1969).
    Immunodeficiency states and immunosuppression therapy are both
    associated with an increased rumour incidence. Immunosuppressive
    agents, such as antilymphocyte serum, enhance both chemically- and
    UVR-induced tumour formation (Nathanson et al., 1973, 1976).


    5.1  Beneficial Effects

        In addition to the direct effects on the skin, UVR produces a
    number of systemic effects. It has the capacity to increase the tonus
    of the sympathico-adrenal system, enhances mitochondrial and
    microsomal enzyme activity and the non-specific immunity level, and
    increases the secretion of a number of hormones (Tung, 1976).

        Systolic and diastolic blood pressures are reduced before sunburn
    appears and may even be reduced with exposures so mild that no visible
    erythema is produced (Aitken, 1937). Blood pressure gradually falls
    for 24 hours, and lowered pressure may persist for several days.
    Studies have demonstrated that the exercise tolerance of children
    receiving UVR through the winter is greater than that of control
    groups not receiving radiation (Ronge, 1948; Zilov, 1971).

        Other changes that have been attributed to UVR exposure include
    reduction in serum cholesterol, increase in the glucose tolerance
    curve, and decrease in serum tyrosine (Kameneckaja & Mitrofanova,

        Seasonal changes in various diseases are often considered to be
    evidence of UVR effects, but there are many other climatic variables
    that change with the season, including temperature and daylength.
    Blood volume, blood content of the skin, blood flow in the skin, and
    hydration of the skin due to sweating vary with seasonal adaptation.
    Thus few changes in disease patterns can be attributed to the effects
    of UVR alone.

        Data have been obtained indicating that the body's tolerance
    towards exposure to chemical substances such as nitrites, benzpyrene,
    carcinogens etc, which produce general toxic, carcinogenic, and
    allergenic effects depends, to some extent, on the degree of exposure
    to UVR (Gabovic et al., 1975; Prokopenko & Zabulueva, 1975;
    Prokopenko, 1976). Prophylactic treatment with UVR preceding specific
    immunization reduces the risk of vaccination allergy and helps to
    increase the effectiveness of the immunization (Talanova et al.,

        Where sizeable populations live in far northern areas, it is now
    generally acknowledged that a long period of UVR deficit may have a
    harmful effect on the human body. Numerous investigations indicate
    that lack of exposure to solar UVR can lead to the development of a
    pathological condition known as "UVR deficiency" or "light
    starvation". The most frequent manifestation of this disease condition
    is a disturbance in mineral metabolism and the development of Vitamin
    D deficiency and rickets in children, accompanied by a sharp reduction
    in the defensive powers of the body, making it particularly vulnerable
    to unfavourable environmental factors. The development of UVR
    deficiency is confirmed by data from a survey conducted, mainly among

    children, in different photoclimatic zones of the USSR (Belikova et
    al., 1975; Dancig, 1975), and from a survey of ships' crews working in
    the north and in the tropics.

         Vitamin D. Sunbathing is popular, and there is a widespread
    feeling that "sunlight is good for you", but the physiological
    benefits that presumably underlie the feeling of well-being have not
    been adequately explained or studied.

        The only thoroughly established beneficial effect of UVR on the
    skin is the conversion of 7-dehydrocholesterol to Vitamin D3. Several
    investigators have helped to promote the understanding of the
    mechanisms of Vitamin D production and its metabolism and functioning.

        It has long been noted that prolonged limitation or complete
    absence of exposure of the human skin to solar UVR makes natural
    activation of Vitamin D impossible and is an important factor in the
    spread among the population of "chronic latent D avitaminosis"
    reflected in widespread rickets and dental caries. Data from the
    previously mentioned survey by Belikova et al. (1975) indicate that,
    despite an overall reduction in the incidence of rickets and in its
    severity, it is still frequent among young children in the north of
    the USSR. Morbidity indices for rickets at latitude 65°N are 2.5-3
    times as high as at latitude 45°N.

        Comparative investigations among healthy children aged 3-6 years
    in the central zone of the USSR and beyond the Polar Circle have also
    confirmed that disturbances in mineral metabolism in children in the
    far north occur earlier and are more marked (Talanova & Zabalueva,

        In this connection, it is of some interest that Vitamin D
    deficiency may have a direct effect on the pathogenesis of dental
    caries (Dancig, 1974).

        The problems associated with UVR deficiency are frequently
    enhanced by social factors and by degree of pigmentation (Loomis,

         Phototherapy. Some information on the beneficial effects of UVR
    comes from the past and present use of sunlight and UVR in medical

        In the pre-antibiotic era, several forms of skin tuberculosis and
    skin infections were treated with UVR. At present, UVR treatment in
    medicine is largely confined to treating skin diseases, such as
    psoriasis, acne, atopic dermatitis, and recurrent boils. There have
    been reports that UVR, administered in gradually increasing doses, has
    been helpful in the treatment of both chronic pneumonia (Boguckij et
    al., 1975), and rheumatic diseases in childhood (Karacevceva, 1971).

    5.2  Induction of Erythema in Human Skin

        Erythema solare, or more commonly "sunburn", consists, in its
    mildest form, of a reddening of the skin that appears 1-6 hours after
    exposure to erythemogenic UVR and gradually fades in 1-3 days. In its
    more severe forms, sunburn results in inflammation, blistering, and
    peeling of the skin; it is followed by tanning of the skin, which
    becomes noticeable within 2 or 3 days of irradiation.

        The amount of radiation required to produce solar erythema
    provides a convenient measure of UVR dosage. The actual amount of
    energy required varies with the wavelength of the radiation, since
    some regions of the spectrum are more effective than others. Because
    of large variations from one individual to another, as well as
    variations between different parts of the body, an "erythema unit"
    cannot be determined with the same accuracy as physical units or even
    units of visual luminosity. There are also appreciable variations in a
    given individual from time to time, depending upon such factors as
    physical condition and previous exposure. The methods for evaluating
    erythema introduce additional variables. There is a latent period
    after exposure before reddening of the skin is observable. Thus, the
    length of time after exposure that the observation is made will affect
    the results. In spite of these limitations, a "sunburn unit" (SU),
    based on the effect of solar UVR on the average untanned human white
    skin, provides a useful method of rating and comparing various sources
    of UVR.

        The use of the SU (Lazarev & Sokolov, 1971) is based upon the
    applicability of the Bunsen-Roscoe law of reciprocity (see section
    4.6.2). Over a reasonable range of exposure times, skin erythema
    depends on the total UVR dose, but is independent of exposure rate and
    duration (Seidl, 1969).

        Monochromatic sources of radiation are not generally considered,
    but the erythemal effectiveness depends upon the sum of the effects of
    those wavelengths that are present. In the case of a line spectrum,
    the total effect is calculated by adding the weighted intensities of
    the various lines of the source, the weighting depending on the action
    spectrum in use.

        By adopting this method, the erythemal equivalent of any
    particular distribution of radiant energy may be calculated and
    expressed as the equivalent amount of energy at a particular
    wavelength (e.g., 296.7 nm) that would produce the same erythemal
    effect as the given heterogenous radiation (section 6).

        Numerous factors contribute to the complexity of the erythema
    response (skin temperature, sweating, dose-rate, etc., section 6). In
    applying the reciprocity law to polychromatic radiation, the fact that
    the observed differences in biological effects of different
    wavelengths may introduce inaccuracies must be considered.

    5.2.1  Action spectra of human skin erythema

        Hausser & Vahle (1927) reported the first precise determination
    of the action spectrum for the erytherna of human skin; a double peak
    was shown with maxima at about 250 and 297 nm and a minimum at about
    280 nm. In these and related studies, the skin of several individuals
    was exposed to UVR from a mercury arc passed through a double-quartz-
    prism monochromator, and the influence of wavelength, exposure time
    and rate of exposure upon the nature, degree, and course of erythema
    was examined. Similar action spectra were published by Coblentz et al.
    (1932), Lukiesh et al. (1939), and Magnus (1977) (Fig. 5).

    5.3  Natural Protection against Erythema-inducing Ultraviolet Radiation

    5.3.1  Melanin (see also section 4.2.3)

        Skin tanning during and following sun exposure is one of the
    major protective devices of the skin against further damage by UVR.
    The UVR range from 290 to 320 nm produces sunburn and subsequent new
    pigment formation. UVR in the range of 320 to 400 nm produces little
    erythema, except at very high doses, but may produce immediate pigment
    darkening and other increases in melanin pigment in those who have
    this capacity.

    FIGURE 5

        Constitutional skin colour in man is the "baseline" colour that
    develops in the absence of exposure to solar radiation or other
    environmental influences and results from genetically determined
    levels of melanin pigmentation. Facultative skin colour or "tan" is
    the increase in melanin pigmentation above the constitutional level
    which is induced by UVR or by pituitary hormones such as the
    melanocyte-stimulating or the adrenocorticotropic hormones. The
    facultative tanning (darkening) response induced by solar irradiation
    can be divided into immediate tanning (IT), which occurs within
    minutes of exposure to sunlight, and delayed tanning (DT), which
    becomes evident several days after exposure (for review see
    Fitzpatrick et al., 1974).

         Immediate tanning (IT). IT, also called immediate pigment
    darkening (IPD), is best seen in pigmented individuals. In general,
    the darker the unexposed, baseline, inherited colouration, the greater
    the ability to exhibit IT.

        Within 5-10 min of exposure to the noonday sun, a gradual
    darkening is noticed, which is confined to exposed skin. If exposure
    continues, darkening increases until it reaches a maximum after about
    1 h of irradiation. The colour ranges from light brown to dark brown
    or, in the more deeply pigmented races, from grey-brown to black.
    Brief exposures to sunlight may lead to slight to moderate IT, which
    begins to fade within 30 min of the end of exposure and is scarcely
    visible after 3-8 h. Prolonged exposure to sunlight or high-intensity
    artificial long wave UVR sources can lead to striking IT that lasts
    longer than 36 hours. IT is optimally produced by both long wave UVR
    and visible light.

         Delayed tanning (DT). DT, also referred to as "true
    melanogenesis", becomes visible 72 hours after exposure to UVR,
    although electron microscope studies have shown ultrastructural
    evidence of the formation of new melanosomes and melanin much earlier.
    The major action spectrum of DT is the same as that for sunburn but DT
    can also follow exposure to UV-C and UV-A and shorter wavelength
    visible light.

        Exposure to UVR can also modify the pattern of distribution of
    melanosomes in keratinocytes. In Mongoloid peoples, repeated UVR
    exposure results in a predominance of non-aggregated single
    melanosomes. Interpretation of variations in melanosome packaging
    within the epidermis must take into account the history of the
    previous exposure of individuals to solar radiation and other factors.

        Once present, melanin acts as a neutral density filter and
    decreases the amounts of UVR that can reach tile lower layer of the
    skin containing viable keratinocytes or penetrate into the dermis to
    strike blood vessels. As constitutional or facultative pigmentation
    increases, the dose of UVR required to produce erythema increases.

    5.3.2  Thickening of the stratum corneum

        Thickening and brownish discoloration of the stratum corneum of
    light-exposed areas of human skin are noted after exposure to UVR.
    While a protective effect unquestionably exists, it is of relatively
    less practical importance than the protection afforded by melanin

    5.4  Solar Elastosis and Other Dermal Effects of Ultraviolet Radiation
         (See also section 4.2)

        Sunlight may have many effects on the skin, and one of the most
    important both clinically and cosmetically is aging. Gross changes in
    actinically damaged skin are a dry, coarse, leathery appearance,
    laxity with wrinkling, and various pigmentary changes. Frequently, in
    elderly and even in some relatively young fair-skinned adults, there
    is a striking difference between light-exposed regions and those
    protected by clothing. A weather-beaten farmer often appears
    considerably older than a clerk of comparable age. Black skin has
    natural protection because of its high melanin content and elderly
    Negroes often appear deceptively young (Silverstone & Searle, 1970).

        It now seems clear that collagen degeneration in the dermis is
    independent of age and is determined simply by the cumulative amount
    of injury from UVR. This depends on the degree and frequency of
    exposure and the extent of natural (and artificial) protection
    afforded to the patient's skin by the thickening of the stratum
    corneum, melanin pigment, clothing, or chemical sunscreens.

        The visible cutaneous changes usually interpreted as "aging" are
    apparently due, to a large extent, to chronic exposure to sunlight.

    5.5  Ultraviolet Radiation and Skin Cancer in Man
         (See also Section 4.2)

        Classical evidence supporting the role of sunlight, particularly
    of UVR, as a causal factor in human skin cancer can mainly be
    summarized in the form of six associations of skin cancer (Urbach et
    al., 1972):

         (a) Association with exposed areas of the skin. Among
    white-skinned people, skin cancers occur most frequently on the parts
    of the body most exposed to sunlight -- the head, neck, arms, and
    hands, and the legs of women.

         (b) Association with protection against UVR. Among races with
    dark skin, in which pigment filters UVR, there is very little skin
    cancer and the disease does not occur predominantly in areas of the
    skin exposed to the sun. Sunburn and skin cancer arise in the same
    tissue, and UVR is known to cause sunburn. It appears that those who
    are more susceptible to skin cancer sunburn more easily. White-skinned
    people of Celtic origin are more susceptible to both skin cancer and
    sunburn while those of Latin origin are less susceptible.

         (c) Association with the amount of exposure to the sun. Among
    fair-skinned people, there appears to be a greater prevalence of skin
    cancer in those who spend more time outdoors.

         (d) Association with the intensity of solar exposure. The
    incidence of skin cancer among white-skinned people increases with
    increasing proximity to the equator and thus with increasing solar
    radiation and intensity of UVR.

         (e) Association with UVR in laboratory studies. Skin cancer can
    be produced in mice with repeated doses of UVR in the same spectral
    range that produces sunburn in the human skin.

         (f) Association with insufficient ability to repair DNA damaged
    by UVR. Those with the recessive disease xeroderma pigmentosum, who
    have a defect in DNA repair, develop skin cancer prematurely. Such
    persons are photosensitive, and develop tumours, induced by exposure
    to solar UVR. They frequently die of skin cancer before reaching adult

    5.5.1  Anatomical distribution of skin cancer

        Numerous studies have shown that, in fair-skinned people, skin
    cancers arise primarily on sites exposed to sunlight. It has been
    demonstrated that about 90% of all basal cell carcinomas and more than
    half of all squamous cell carcinomas occur on the head and neck. The
    majority of those squamous cell cancers not occurring on the head and
    neck are found on the hands and forearms; the ears of females are
    markedly protected by hair (Silverstone & Searle, 1970; Swanbeck &
    Hillstrom, 1971).

        Comparing the sites of non-melanoma cancers with studies made of
    the geometry of insolation of the head and neck areas, it becomes
    clear that two thirds of all basal cell carcinomas occur on the skin
    sites receiving the highest doses of UVR, and that virtually all
    squamous cell carcinomas occur at these sites (Urbach et al., 1972).

        The anatomical distribution of malignant melanoma, a less common
    but more deadly form of skin cancer, suggests a less striking
    association with UVR exposure. However, there has been a considerable
    increase in the prevalence of this type of cancer on the legs of women
    during the past 25 years and a special form of melanoma, lentigo
    maligna, almost always arises on the face.

    5.5.2  Occupation and skin cancer

        As has been pointed out previously, surveys of the incidence of
    skin cancer other than malignant melanoma are, generally, not very
    reliable. Consequently, data concerning the relationship between
    occupation and skin cancer incidence are also scarce. From the studies
    carried out in Queensland, Australia, and in Galway, Ireland, the most
    reliable sources, it appears that those in outdoor occupations are the

    most highly exposed and, therefore, at the highest risk. Thus farmers,
    fishermen, sailors, and others such as road workers, roofers,
    policemen, and postmen, have a higher incidence of skin cancer than
    office and factory workers (Swanbeck & Hillstörm, 1971; Gordon &
    Silverstone, 1976).

    5.5.3  Genetics and skin cancer

        In several carefully controlled studies comparing patients with
    non-melanoma and melanoma skin cancer to age-sex matched controls from
    the same populations, a distinct association was found between skin
    cancer and light coloured eyes, fair complexion, light hair colour,
    poor ability to tan, ease of sunburning, and a history of repeated
    severe sunburn. Furthermore, whenever looked for, there was a higher
    prevalence of Celtic stock among skin cancer patients (Silverstone &
    Searle, 1970; Urbach et al., 1972). Xeroderma pigmentosum (XP) is a
    hereditary skin disease in man. Studies on cells from the patients
    have supplied the most decisive arguments regarding the relationships
    between photolesion repair and carcinogenesis. Persons suffering from
    this disease show abnormal pigmentation and a high incidence of skin
    cancers triggered off by exposure to the solar UVR. Cleaver (1973),
    who was the first to draw attention to the possible causes of the
    disease, has written a critical review of the main biochemical and
    genetic studies which reveal the extreme complexity, but also the
    ingenuity and logic of the molecular processes that play a part in the
    development of the disease.

        In general, it has proved possible to establish a correlation
    between the level of DNA repair and the seriousness of the symptoms in
    XP patients.

        Numerous and more complex studies have shown that the various
    degrees of UVR sensitivity observed in XP patients correspond to
    different sensitivity mutants. Using techniques such as cell fusion
    and complementation, several groups have been distinguished that are
    characterized by various defects in the repair mechanisms (Kraemer et
    al., 1975). Some mutants show normal excision but no repair synthesis
    (Lehmann et al., 1975). In others, repair replication would seem to be
    normal, but chain breaks appear more slowly than in normal cells.
    Caffeine emphasizes these differences still further (Fornace et al.,

        Although the mechanisms are far from completely elucidated, they
    show the considerable value of this kind of genetic disorder, in which
    the problems of the photolesions and their repair and of
    carcinogenesis are intimately linked.

    5.5.4  Geographical distribution of non-melanoma skin cancer

        Incidence data for skin cancer, other than melanoma, must be
    treated with considerable reserve. Many cancer registries do not
    register non-melanoma skin cancer at all, and those that do are
    uniformly incomplete, since most of these tumours are treated in
    physicians' offices and either not reported at all or reported without
    histological verification.

        A survey of the recorded geographical distribution of
    non-melanoma skin cancer has been made by Cutchis (1978) (Fig. 6 and
    7). From the data of Scotto et al. (1974), it appears that in Iowa,
    USA, for instance, the incidence of skin cancer in males rose from
    61.4/100 000 in 1950 to 174/100 000 in 1972. This approximately 3-fold
    increase is also noticeable in all areas in Texas, with the exception
    of El Paso, where the incidence rate actually decreased, and Houston,
    where the increase was apparently only 2-fold. The Texas data
    (MacDonald, 1976) showed that incidence rates increased with
    descending latitude, but not in a stepwise fashion. In the most recent
    5-year period (1962-1966), the rate for El Paso was 183/100 000 and
    that for San Antonio (1° further south) was 147.35/100 000. In San
    Antonio, a large part of the permanent population consisted of retired
    military personnel and their families. Most of these people had spent
    much less time in the sunny south than the permanent population in El
    Paso. The highest incidence rate was found at Corpus Christi at
    latitude 28°N (371/100 000). This was significantly greater than the
    incidence at Harlingen (284.5/100 000), at latitude 26°N. At Corpus
    Christi, there was another factor involved besides exposure, i.e., a
    great preponderance of Celtic inhabitants whose forebears migrated to
    that area about a century ago. Thus the disproportionately high
    incidence of skin cancer in Corpus Christi could be due to a
    combination of intense insolation and a very susceptible population, a
    situation similar to that existing in Queensland, Australia.

        These findings demonstrate how important the confounding social
    factors can be in evaluating skin cancer statistics in relation to UVR

         Europe. In Europe, just as in the USA and Australia, a marked
    north-south gradient of non-melanoma skin cancer exists.

        In 1976, Waterhouse et al. reported skin cancer incidence rates
    for males and females as follows: Sweden -- 10.6 and 6.5/100 000;
    Denmark -- 33.4 and 24.5; Federal Republic of Germany -- 7.3 and 4.6;
    UK -- 40.3 and 21.4; and Yogoslavia -- 23.2 and 22.8. Other reports
    suggest incidences in the German Democratic Republic of 43.9 and
    40.3/100 000 (Herold & Berndt, 1968), and in Bulgaria, of 42.2 for
    rural and 25.0 for urban people (Anchev et al., 1968).

    FIGURE 6

    FIGURE 7

        In the USSR, skin cancer morbidity increases from north to south.
    According to these data, skin cancer represents 15-26% of the total
    cancer morbidity in the south, and 9-14° in the north (Caklin, 1974).

         Africa. Information concerning skin cancer in Africa, gathered
    from various sources, but mainly from the reports of Oettle (1962) and
    Davies et al. (1965), show that the native Africans have extremely low
    rates of both non-melanoma and melanoma skin cancer.

        The incidence rates in the Johannesburg Bantus and in Uganda are
    of the order of 1-2/100 000 for non-melanoma skin cancer (almost all
    squamous cell carcinomas of the lower extremities) and 0.4-0.6/100 000
    for malignant melanoma (almost all located on the foot) (Oettle,
    1962). A more recent study in the Sudan shows a somewhat higher
    incidence rate, particularly for squamous cell carcinomas (Malik et
    al., 1974).

        The exceptions are albino Negroes, who are extremely prone to the
    development of skin cancer. In South Africa, albinism is quite common
    among the Bantus. Oettle (1962) estimated a crude annual incidence
    rate of 579/100 000 for male and 408/100 000 for female albino Bantus
    for squamous cell carcinomas of the skin. Interestingly, the rates for
    basal cell carcinoma were recorded as only 36/100 000 for both sexes
    combined, as only 1 case was found.

         India. Incidence data for skin cancer in India are not
    available. However, it is clear that the majority of skin cancers seen
    in hospitals occur in fair-skinned people. Among native indians,
    special types of squamous cell carcinomas of the skin are found such
    as the Kangri, Dhoti, and Chutta cancers, which are presumably due to
    extreme heat, smoke, and chronic friction (Mulay, 1962).

         China and Japan. While incidence figures are again not
    available, it is clear that skin cancer is uncommon in the Province of
    Taiwan, China, and Japan. This is also borne out by a reversal of the
    usual basal cell to squamous cell carcinoma ratio. Squamous cell
    carcinomas are 2-3 times more common than basal cell cancers, and may
    arise at the site of premalignant skin changes such as burns, chronic
    trauma, or secondary to arsenic ingestion (Miyaji, 1962; Yeh, 1962).

         Australia and New Zealand. Probably the best skin cancer
    surveys of recent years have been carried out in Australia,
    particularly in Queensland, by Gordon & Silverstone (1976). Their
    values for the incidence of skin cancer in various parts of Australia
    are reported in Table 5.

    Table 5.  Skin cancer in Australiaa

    Annual incidence per 100 000 population

                                 Male                   Female

                                         Age                     Age
                           Crude    standardized   Crude    standardized

    Victoria (40°S)          68.5        66.6        50.5        38.5
    Queensland              265.1       265.1       174         155.8
      Brisbane (28°S)       242                     172
      Townsville (19°S)     466                     300


    a From: Gordon & Silverstone (1976).

        Comparable demographic data in those areas of the world that are
    warm and sunny and to which people from northern Europe including the
    United Kingdom have migrated are given in Table 6.

    Table 6.  Examples of high incidence of skin cancer. Annual incidence
              per 100 000 population by sexa

              Region                  Male       Female      Latitude

    S.W. England                       28        15          53°N
    South Africa -- Cape Whites       133        72          35°--25°S
    Texas (non-Latin)                 168        106         28°--32°N
    Queensland (Whites)               265        156         28°--10°S


    a From: Gordon & Silverstone (1976).

        Skin cancer tends to appear at a much earlier age in the
    Queensland population than in populations living further away from the

        If the distribution of annual solar UVR (Green et al., 1975) is
    plotted against the incidence of skin cancer on a global basis, it can
    be shown that skin cancer incidence doubles for every 10° decrease in
    latitude. The Australian data would fit this concept, particularly in
    Queensland, where the difference in incidence between Brisbane and
    Townsville is about two to one and the difference in latitude about

        Not as much work on skin cancers has been done in New Zealand as
    in Australia; however good estimates of skin cancer incidence have
    been reported by Eastcott (1962). These are: 113/100 000 for basal
    cell carcinoma, 38/100 000 for squamous cell carcinoma; and
    5.5/100 000 for malignant melanoma. These rates are considerable
    lower than those for Australia, but New Zealand is much further from
    the equator and thus receives less UVR.

    5.5.5  Dose-response relationship for skin cancer (see also 
           section 4.5.2)

        Although a correlation between the incidence of skin malignancy
    and solar UVR levels has not yet been established with great accuracy,
    it has been possible to demonstrate a correlation between latitude and
    skin cancer incidence (Gordon & Silverstone (1976), Fig. 8). Some
    confounding factors have been obtained from animal experiments.

    FIGURE 8

        There are data that indicate that physical and chemical factors
    may attenuate or intensify the carcinogenic effect of UVR
    (Sviderskaja, 1971). Chronic exposure of animals to small doses of
    ionizing radiation reduces resistance to the carcinogenic effects of
    UVR, increasing the incidence and reducing the length of the latent
    period. UV-B radiation has variable effects on the growth of
    transplanted and chemically induced tumours. UV-B radiation can affect
    the resistance of the body to tumour formation, increasing it with use
    of sub-erythemal doses and considerably reducing it with large doses
    (Dancig et al., 1975). These data, although obtained in animal systems
    only, may be of great significance for human health, since the
    resistance of the body to exposure to various harmful factors in the
    environment operates against a certain background of natural UVR.

    5.5.6  Mortality from skin cancer

        In contrast to malignant melanoma, where mortality in most series
    stiff exceeds 40%, the fatality rate in non-melanoma skin cancer is as
    low as 1%. However, it would be incorrect to try to draw conclusions
    from disease specific mortality rates.

    5.5.7  Malignant melanoma

        Both the incidence and the mortality rates of malignant melanoma
    are rising rapidly in all countries in which they have been studied,
    with mortality rates doubling in a 10-15 year period (Elwood & Lee,

        The incidence varies from less than 1/100 000 in Japan, Nigeria,
    and India to as high as 24/100 000 in Queensland, Australia. The rise
    in incidence and mortality has been much greater in younger people
    than in those over 65 years of age, implying that a causal mechanism
    operates from an early age. The increase has been greater at certain
    body sites and thus the site distribution has changed. The most
    striking increase in incidence has been on the lower limbs in females
    and the trunk in men (MacGovern, 1977).

        In countries where such data are available, there is a distinct
    association between latitude of residence and development of malignant
    melanoma (Lancaster, 1956; Magnus, 1973; Movshovitz & Modan, 1973;
    Elwood et al., 1974). The closer to the equator and the longer the
    residence in countries with high insolation, the higher, in general,
    is the incidence of malignant melanoma.

        However, while there is usually a demonstrable latitude gradient
    within a country, the latitude association in much less marked than
    that for non-melanoma skin cancer. For instance, incidence rates for
    malignant melanoma in Norway and Sweden are much higher than in
    England and France both of which are much further south (Cutchis,
    1978, Fig. 6 and 7).

        Basal cell and squamous cell carcinoma, which are considered to
    be due primarily to chronic UV-B exposure, are commonest on the areas
    of skin exposed to sunlight, occur at a later age than malignant
    melanoma, and are strikingly associated with severe solar damage to
    the skin. In contrast, malignant melanoma occur more often on the
    trunk of men and legs of women than non-melanoma skin cancer, and only
    one type, the lentigo maligna melanoma (comprising not more than 15%
    of all melanoma), is associated with histological UVR-induced skin
    damage (McGovern & Mackie, 1959).

        Thus, it appears that non-melanoma and melanoma skin cancers are
    related to UVR exposure in different ways. Table 7 lists the
    similarities and differences between these two types of tumours.
    Parallel increases in melanoma and non-melanoma skin cancer cannot be
    expected, as the latent period for malignant melanoma is apparently
    much shorter than that for non-melanoma skin cancer. Reasons suggested
    for the differences between the two types include: the greater
    sensitivity of melanocytes to UVR (McGovern, 1977); the presence of
    some secondarily produced circulating factor (Lee & Merrill, 1970);
    and intermittent overdoses of UVR (Fears et al., 1977).

        In the absence of an experimental animal model, and with the
    present state of knowledge, it must be assumed that there is some
    association between UVR and the development of malignant melanoma.
    Thus any additional UVR exposure of susceptible individuals may
    increase the risk of development of this very serious malignant skin

    5.6  Phototoxic and Photoallergic Diseases

    5.6.1  Phototoxicity

        Light-induced damage to the skin that does not depend on an
    allergic mechanism may be considered phototoxic. Theoretically, these
    reactions will occur in everyone, if the skin is exposed to enough
    light energy of the proper wavelengths and if enough molecules that
    will absorb these wavelengths are present. The radiation must
    penetrate to the absorbing molecules for the reaction to occur.
    Clinically, phototoxic reactions are usually characterized by erythema
    (and at times oedema) occurring from a few minutes to several hours
    after exposure, followed by hyperpigmentation and desquamation. The
    sunburn reaction is the classical example of response to a phototoxic
    effect (Ippen, 1969).

        Table 7. Comparison of epidemiological factors in the etiology of malignant melanoma and
             non-melanoma skin cancer

             Factor                  Malignant melanoma                 Non-melanoma skin cancer

    Latitude of residence         Increases linearly within          Increases geometrically with
                                  countries, Incidence not           latitude.
                                  strictly related to latitude

    Age of onset                  3rd and 4th decade most            6th to 8th decade most common.

    Sex                           Moderate preponderance for         Great preponderance for males.

    Anatomical distribution:      Back, anterior torso, upper        Head and neck (particularly ears
    Male, white                   extremity, head, and neck.         and lip), upper back, hand,
                                                                     upper extremity.

    Anatomical distribution:      Back, lower leg, upper             Head and neck (ears and lower
    female white                  extremity, head, and neck.         lip, spared), hands, upper
                                                                     extremity, anterior chest.

    Anatomical distribution:      Soles, mucous membranes            Anterior lower extremities, other
    Black and oriental            palms, nail bed. (all sites        (all sites rare).

    Racial (genetic) factors      Celtic background, Scandinavians   Celtic background, Scandinavians.
                                  Rare in pigmented races.           Rare in pigmented races.

    Table 7 (contd).


             Factor                  Malignant melanoma                 Non-melanoma skin cancer

    Possible etiological          Genetic (xeroderma pigmentosum     Genetic (XP)
    factors                       XP, B-K mole)                      Physical (UVR, X-ray)
                                  Physical (UVR, trauma)             Chemical (arsenic, coal tar).
                                  Chemical (PCBsa, alpha-DOPA)
                                  Developmental (nevi)


    a PCBs = polychlorinated biphenyls.

        From the clinical point of view, the erythema produced by various
    phototoxic agents differs greatly in type of onset and type of
    reaction; the ability of the agents to elicit pigmentation also

        In contrast to the usual acute solar erythema, which begins after
    a latent period of a few hours, peaks at 24 h, and subsides in a few
    days to be replaced by moderate melanin pigmentation, the erythema due
    to photodynamic compounds appears immediately after or during
    radiation, may be associated with striking wheal formation, and
    disappears in 3-6 h. Pigmentation is usually minimal.

        The erythema due to furocoumarins (8-MOP) begins later than that
    caused by solar radiation, peaks at 48-72 h, may persist for days, and
    is followed by very intense pigmentation.

        Despite a considerable amount of investigation, the mechanisms by
    which phototoxic responses occur are not well understood. In the case
    of the exogenous photosensitizer, either the molecule alone or a
    complex of the chemical and cellular organelles becomes excited by the
    absorption of light; triplet states and free radicals, or both, may be

        Certain dyes and chemicals such as methylene blue, acriflavine,
    rose bengal, and porphyrins produce photochemical effects on living
    and non-living substrates only in the presence of oxygen. The
    photo-dynamically active substance becomes excited and forms a triplet
    state or a free radical. The excited chemical may also form peroxides
    and then oxidize the substrate. Other possibilities include passing
    the energy from the excited chemical to the biological substrate,
    which then becomes oxidized, or the activated chemical may be able to
    accept electrons, resulting in the oxidation of the substrate. After
    excitation, the photosensitizing molecules return to the ground state
    and are structurally unchanged.

        Photosensitizing compounds may be endogenous, i.e., formed in the
    body, usually by abnormal metabolism (e.g., porphyrins), or exogenous,
    i.e., contacted externally or given as medication.

        Exogenous photosensitizers may reach the skin by topical or
    systemic routes and the reactions may be phototoxic or photoallergic
    in nature. The action spectra for most of the phototoxic agents that
    may cause skin disorders in man lie in the long-wavelength UVR range
    (320-400 nm).

         Contact photosensitizers include: cosmetics such as perfumes,
    colognes, after-shave lotions (essential oils and psoralens),
    lipsticks (fluorescein derivatives), creams, and hair preparations
    (coal tar derivatives); and plants that cause phytophotodermatitis
    such as Persian limes, pink rot-infested celery, many members of the
    Umbelliferae and Rutaceae orders. These problems are primarily due to

    psoralen compounds and therapeutic agents including phenothiazines and
    sulfonamides (usually used therapeutically), halogenated
    salicylanilides, sunscreens, and blankophores (usually photoallergic).

         Systemic photosensitizers include: thiazide diuretics;
    antibacterial sulfonamides; sulfonylurea antidiabetic drugs;
    phenothiazines (especially chlorpromazine); and antibiotics
    (especially dimethylchlortetracycline).

        A large number of other drugs may occasionally induce

    5.6.2  Photoallergy

        Photoallergy can be defined as an acquired altered capacity of
    the skin to react to light energy alone or in the presence of a
    photosensitizer (Harber & Baer, 1969).

        In photoallergic reactions, the photosensitizer leads to the
    formation of the photohapten, which binds (covalently) with a suitable
    carrier molecule to form the complete photoantigen. The carrier may be
    a protein, polypeptide, mucopolypeptide, mucopolysaccharide, or other
    macromolecule present in the skin. Once developed, photoallergy can
    apparently occur with light energy alone, but presumably small
    quantitites of the photoantigen are still present in the skin and
    involve a circulating antibody or a cell-mediated response. In
    contrast to phototoxicity, photoallergy is uncommon and is
    characterized clinically by such reactions as immediate urticaria or
    delayed papular or eczematous responses similar to contact dermatitis.

        The hallmark of a sunlight-induced reaction, whether toxic or
    allergic, is the distribution of the eruption. The exposed areas of
    the face, neck, upper extremities, and, in women, the anterior surface
    of the legs and the proximal, dorsal areas of the feet are mainly
    involved. Exposure while driving may accentuate the eruption on the
    side of the face and arm adjacent to the window. The upper eyelids,
    subnasal and submental areas, flexural aspects of the wrists, and the
    antecubital fossae tend to be spared. Clothing generally provides
    protection, but reactions can be produced by penetration of UVR
    especially through the light fabrics worn in summer.

        The most common photoallergens are: 3,5-dibromosalicylanilide
    (3,5 DBS); 4,5 dibromosalicylanilide (4,5 DBS); tribromosalicylanilide
    (TBS); hexachlorophene; bithionol; and trichlorcarbanilide.

    5.7  Pterygium and Cancer of the Eye

        While detailed epidemiological evidence does not seem to exist,
    there is a clinical impression among competent ophthalmologists that a
    latitude gradient exists for the development of pterygium of the eye,
    a benign hyperplasia of the bulbar conjunctiva which may eventually
    interfere with vision by growing over the pupil (Dolezova, 1976).

        Epidermoid carcinoma of the bulbar conjunctiva is a rare neoplasm
    which appears with increased frequency in people living in the tropics
    or subtropics (Afghanistan, Colombia, Ethiopia, Haiti, Malawi, Middle
    East, Nigeria, Pakistan, Senegal, South Africa, and Uganda). It has
    also been reported in cattle in the same region. Such tumours of the
    eye can be induced in experimental animals with artificial UVR. Early
    lesions, which are exophytic and tend to be papillary, are often
    accompanied by basophilic degeneration of subepithelial collagen and
    chronic inflammation.

        The tumours are moderately to poorly differentiated keratinizing
    epidermoid carcinomas.

        In contrast to carcinoma of the skin, carcinoma of the eye is
    more common in dark-skinned people, probably because of much greater
    UVR exposure, and lack of pigment in the conjunctiva.


    6.1  The Significance and Extent of Different Environmental Sources of
         Ultraviolet Radiation and Pathways of Exposure

        The major health risks from natural UVR arise from chronic,
    excessive, and unwise exposure to solar radiation. Section 2.1.1 of
    this document describes in detail the wavelengths and quantities of
    solar UVR that reach the earth and factors affecting it.

        Briefly, depending on latitude and stratospheric ozone
    concentration, the shortest wavelength measured (at noon, near the
    equator) in solar radiation is about 290 nm. In most regions of earth,
    the lower cut-off limit is at about 295 nm. The spectral composition
    and radiation intensity of solar UVR is greatly influenced by
    latitude, season, time of day (i.e., angle of the sun), cloud cover,
    and the albedo of the surface. About two thirds of the skin-erythema-
    producing solar UVR reaches the earth between 10h00 and 14h00.

        In man, the extent of human exposure to solar UVR varies with
    posture. In the upright position, esentially only portions of the
    head, back of the neck, shoulders, forearms, and hands are exposed. In
    addition, the skin of the thighs and upper arms may be heavily

    exposed in some occupations such as driving a tractor. Exposure also
    varies with time of day and local weather conditions; clothing
    (wearing of hats, short- or long-sleeved shirts, shorts, etc.); work
    and social habits; and ground albedo (snow, ice, and sand being the
    only effective reflectors).

        The maximum amount of solar UVR to which an individual could be
    exposed in one day, represents about 25 minimal erythema skin doses,
    i.e., about 7500 J/m2 of radiation equivalent to the skin erythema
    effect of 297 nm monochromatic UVR.

        Occupational exposure from artificial sources is either
    inadvertent, when the sources produce UVR as a by-product, or
    deliberate, when sources are designed to generate UVR to use its
    properties. Depending on the characteristics of the source (section
    2.1), the spectral composition of the emitted UVR can contain
    wavelengths in the UV-A, UV-B, and UV-C regions.

        Some industrial processes in which UV energy is a by-product are
    welding, plasma torch operations, photoelectric scanning, and hot
    metal operations. Because of the germicidal properties of certain
    portions of the UV spectrum, artificial sources are used in hospitals,
    biological laboratories, schools, and industry. Other common
    applications are illumination, advertising, crime detection, chemical
    synthesis and analysis, photoengraving, food, water, and air
    sterilization, vitamin production, and medical diagnosis. Many other
    occupations are listed in Table 8. New sources, such as UV lasers and
    fluorescent panels, are being developed.

        Table 8.  Occupations potentially associated with UVR exposure

    aircraft workers           furnace workers                oil field workers
    barbers                    gardeners                      pipeline workers
    bath attendants            gas mantle workers             plasma torch operators
    brick layers               glass blowers                  printers railroad track workers
    burners, metal             glass furnace workers          ranchers
    cattleman                  hairdressers                   road workers
    construction workers       herders                        seamen
    cutters, metal             iron workers                   skimmers, glass
    drug makers                lifeguards                     steel mill workers
    electricians               lithographers                  stockmen
    farmers                    metal casting inspectors       stokers
    fisherman                  miners, open pit               tobacco irradiators
    food irradiators           nurses                         vitamin D preparation makers
    foundry workers                                           welders


        The amount of UVR exposure from artificial sources depends on the
    spectral composition, radiant intensity, distance from source,
    shielding, etc., and must de determined for individual conditions.

    6.2  Types of Biological Effects and Their Significance for Human

        Since UVR penetrates essentially only into the skin and eyes of
    man, the deleterious effects on these organs are of the greatest
    importance. The acute and chronic effects of UVR are described in
    detail in sections 4 and 5. Also of concern, however, are the
    deleterious effects of "UVR deficiency" which can occur at latitudes
    of about 60° (section 7.2).

        Acute effects of UVR in the 250-320 nm wavelength range consist
    of reddening, swelling, and blistering of the skin, occurring 3-24 h
    after exposure, followed in 3-6 days by the production of melanin
    ("suntan"), in those capable of producing this pigment.

        Acute effects on the eye consist of painful keratoconjunctivitis,
    which recedes in 36-48 h.

        After many years of repeated UVR exposure, the skin of
    susceptible individuals becomes leathery, wrinkled, and discoloured
    ("aging changes") and skin cancer may develop (sections 5.4 and 5.5).
    The degree to which these changes develop depends not only on the UVR
    dose, but also, to a large extent, on the genetic background, and
    particularly on the ability of the skin to pigment. For this reason,
    "aging" changes and skin cancer are very much less common in
    genetically heavily pigmented individuals.

        The development of "aging" changes is irreversible, and presents
    a major cosmetic (and thus psychological) problem, particularly for

        While skin cancer, with the exception of malignant melanoma, is
    rarely fatal, it constitutes a social burden in terms of loss of work,
    and medical expenses.

    6.3  The Risk Associated with Combined Exposure with Other Agents

        The interaction of UVR of various wavelengths, particularly UV-A
    (320-400 nm), with natural and artificial chemical agents may result
    in a variety of deleterious effect not elicited by UVR or the chemical
    agents alone.

        Among the most common of these effects are the phenomena of
    phototoxicity, photoallergy, and chemically enhanced
    photocarcinogenesis (sections 4.5 and 5.6). Fortunately, the actual
    risk from such photobiological responses is small, as yet.

        Of the phototoxic agents, the psoralens (furocoumarins) occur in
    the rind of most citrus fruit, and in many green leafy plants. Contact
    occurs most often in fruit pickers, others involved in the citrus
    industry, and through the use of bergamot-containing perfumes. The
    phototoxic reactions simulate sunburn. Acute skin and eye
    phototoxicity are frequent, and sometimes serious, problems in workers
    handling tars, such as roofers and road workers. Similar findings have
    been made in creosote workers (Emmett, 1977a). Chronic phototoxicity,
    and perhaps enhancement of carcinogenicity can also be induced by coal
    tar products and phenanthrene carcinogen-containing materials. At risk
    are roofers, road workers, and those in the tar and pitch-using
    industries. The extent of augmentation of photocarcinogenesis in man
    by this route is not known.

        The introduction of man-made photoactive chemicals into the
    environment is increasing. Serious, although small, outbreaks of
    photoallergic reactions have been reported caused by soap additives
    (halogenated salicylanilides), antibiotics (bithionol, griseofulvin),
    drugs (chlortetracycline, thiazides, chlorpromazine), and, most
    recently, compounds deliberately used in photochemical processes, such
    as printing inks (Emmett, 1977b).

        As yet, the risk of such reactions occurring is very small, but
    with the continued introduction of new chemicals into the environment,
    it is bound to increase.

    6.4  The Population at Risk -- Geographical Distribution, Genetic
         Influences and Occupation

        As far as exposure to solar UVR is concerned, virtually the whole
    of the world's population is at some risk. However, the degree of risk
    varies greatly.

        Of primary importance is the geographical distribution of the
    population. Between latitudes 30° and 50°, the intensity and amount
    (dose) of erythema-effective (and presumably carcinogenic) solar UVR
    increases linearly with latitude towards the equator. This increase,
    however, is modified by such conditions as cloud cover, the presence
    of aerosols and "smog", the altitude above sea level (approximately a
    15% increase in UVR for each 1000 metres elevation), and the degree of
    obstruction of the sky by mountains, buildings, trees, etc.

        Another factor of importance is genetic. Constitutional skin
    pigmentation acts as a highly protective factor against the
    deleterious effects of UVR on skin. Consequently, at least as far as
    advanced "aging" changes and skin cancer are concerned, only subjects
    with minimal or slight constitutional pigmentation are at risk. More
    than two thirds of the world's population is more or less dark skinned
    and has little chance of developing such UVR-induced changes. However,
    pale skinned human beings living in tropical climates run a very high
    risk of developing skin cancer. The highest incidence of solar skin
    neoplasms exists in Queensland, Australia, where the combination of a

    primarily Northern European and Celtic population and a latitude near
    the equator results in a greater risk from occupational and social
    outdoor exposure. In contrast, little skin cancer is found in the
    native populations of tropical Africa, although latitude and exposure
    are similar.

        Table 9 shows the best available estimate of the number of
    workers at risk from industrial exposure to various sources of UVR in
    the USA. Data from other countries were not available to the Task

    Table 9.  Number of workers exposed to UVR (estimate from
              Chicago Metropolitan Survey extrapolated to the
              population of the USA)

        standard industrial classifications 19-39          211 000

     Transportation and communication
        standard industrial classifications 40-49           49 000

     Wholesale, miscellaneous retail, service stations
        standard industrial classifications 50, 55, 59      17 000

        standard industrial classifications 79-89           41 000

                                                 Total     320 000

        As already pointed out, workers in many occupations are exposed
    to various levels of artificial UVR.

    6.5  The Reliability and Range of Known Dose-Effect and Dose-Response

    6.5.1  Dose-effect curves for acute skin erythema

        Erythema due to 254 nm radiation appears within 3-4 h of
    exposure, reaches a peak between 8 and 12 h, and begins to subside
    markedly by 24 h. Even at its peak intensity, the colour is a pale
    pink-red, and it is very difficult to be certain of the minimal
    erythema dose. At very low doses (of the order of less than 50 J/m2),
    a weak effect can be recognized, which is clearly (because of the
    shape and reasonably sharp borders) produced by the radiation.
    However, it is not clear that this represents true erythema; the
    colour is yellowish brown and seems to be extremely superficial,
    almost on the surface of the skin. As reported by Hausser, even five
    times the minimal erythema dose does not produce any severe erythema
    at a wavelength of 254 nm. In contrast, with the minimal erythema dose

    (MED) for wavelengths from 280-313 nm, the erythema is quite sharply
    defined. The erythema produced by wavelengths 297, 303, and 313 nm is
    deep red-purple and peaks in 24-28 h. It persists for 3-5 days and
    imperceptibly changes into pigmentation.

    6.5.2  Averages and limits, minimal, and slightly more than minimal
           erythema doses

        The great effect of time after irradiation and of choice of
    degree of redness on the "action spectrum" of human skin is shown in
    Fig. 9 and Table 10. Preliminary experiments suggest that the true
    sensitivity peak lies between 290 and 294 nm. From 297 nm on, there
    appears to be remarkably good agreement between most published
    figures. The disagreement at shorter wavelengths is clearly because of
    differences in time of evaluation, the difficulties inherent in the
    delineation of "minimal erythema", and possible differences in skin

        Furthermore, if an erythema grade slightly above minimal is used
    as a reference point, the resultant action spectrum closely approaches
    that originally described by Hausser & Vahle (Fig. 10).

    Table 10.  Averages and limits (J/m2) for minimal erythema doses 
               (MED) read at 8 and 24 h and for a "moderate" erythema dose
               read at 24 h (30 R). All radiation given at the second 
               exit slit, bandwidth 2.16 nm.a

    nm             MED 8 h            MED 24 h              30 R 24 h
                   (J/m2)              (J/m2)                (J/m2)

    254              63 (35-84)        100 (60-170)         194 (100-400)
    280             140 (50-240)       220 (120-336)        320 (230-480)
    297             140 (60-240)       140 (60-240)         140 (70-200)
    303             390 (280-480)      410 (340-480)        450 (400-480)
    313            6320 (4500-7700)   6800 (5400-7700)     7240


    a From: Berger et al. (1967).

    FIGURE 9

    FIGURE 10

    6.5.3  The "erythema range" effect

        One of the important observations of Hausser & Vahle (1922) was
    that there appeared to be a significant difference between the doses
    needed to produce slight and maximal erytherna at different
    wavelengths. This concept is of great potential significance for the
    prevention of sunburn and the understanding of diseases due to light.
    In Fig. 10, data are plotted from an experiment designed by Hausser to
    test this effect, which show that 5 times the minimal erytherna dose
    produces much less than the maximal erytherna at 254 nm, while 2.5
    times the minimal erythema dose produces maximal erytherna at 303 nm.
    While it takes much more energy to produce any erytherna at 303 nm
    than at 254 nm, not much more than the threshold dose produces a
    significant burn.

        These observations are of great importance because they show that
    the acute biological effects of several wavelengths in the UV-B
    proceed at different time scales, and have very different
    dose-response relationships. Thus, the usual assumptions that it is
    realistic to weight the effectiveness of different wavelengths in a
    continuous UVR source (such as the sun) by an action spectrum obtained
    for a threshold effect with a monochromator is not correct, nor is it
    appropriate to consider the effect of these wavelengths to be
    biologically equivalent.

        Unfortunately, in the absence of knowledge of chromophores or
    biological mechanisms, there is no better way of comparing the
    effectiveness of sources of different UVR composition than the present
    method of calculating the skin erytherna effectiveness of UV-B.

        As in all photobiological cutaneous effects, pigmentation plays a
    major role in the sensitivity of the skin to UVR. Heavily pigmented
    people are 10-20 times less sensitive than untanned fair-skinned
    people. As far as is known, the action spectra for erythema are
    similar for all races, differing only in the amount of energy
    necessary to produce threshold effects.

    6.5.4  Dose-response curves for keratoconjunctivitis

        These are essentially similar to those for erythema, except that
    the peak of the action spectrum is located at 270 nm. This is most
    likely because of the absence of a filtering stratum corneum and
    because the conjunctiva is not pigmented. The peak of 270 nm is
    therefore used for the normalization of the dose limits of broad band

    6.5.5  Dose-response relationship for photocarcinogenesis

        Most of the existing evidence is consistent with the concepts
    that UV-induced photodamage to skin is the main causal factor in the
    development of skin cancer, that the development of skin cancer is a
    stochastic effect, and that there is no threshold (sections 4.3 and

        Thus, a relationship should exist between skin cancer incidence
    and accumulated dose, using a sensitivity function. In mice, the
    quantitative relationship between UVR dose and the production of skin
    cancer has been thoroughly explored; tumour incidence in this
    experimental model is proportional to the square root of the number of
    doses, the dose size, and the interval between doses.

        In man, there is ample evidence that a latitude gradient exists
    for the incidence of skin cancer in sensitive, fair-skinned
    populations, and that this gradient is non-linear. There is obviously
    a relationship between latitude and the intensity of solar radiation,
    and this gradient is exaggerated in the UVR portion of the spectrum.
    Although the shape of this relationship is relatively complex and
    depends on a number of variables, for a range of mid-latitudes
    (30°-50°), both the theoretical form and that obtained from actual
    field measurements closely approximate a straight line. It is
    generally accepted that latitude-related climatic and environmental
    conditions and behavioural effects must modify the UVR dose actually
    reaching a population. The factors involved, and their magnitude are
    largely speculative.

        A series of mathematical models relating human skin cancer
    incidence to solar UVR has been proposed at various times in the past
    few years, because of concern about alteration of the stratospheric
    ozone layer (Green et al., 1978; Rundel & Nachtwey, 1978). While the
    uncertainties are very great, the best accepted model data suggest
    that a 5% increase in erythema-effective solar UVR may result in a 15%
    (range 7.5-25%) increase in skin cancer in a susceptible population
    after about 60 years, when a steady state has been reached. As far as
    the relative risk is concerned in susceptible white-skinned
    populations, people in older age groups, with fair skin that sunburns
    easily and with a high life-time solar exposure, run 10-20 times more
    risk of developing skin cancer than their contemporaries, who tan
    easily and have a low life-time solar exposure (Vitaliano, 1978).
    Incidences of nonmelanoma skin cancer as high as 350/100 000
    population per year have been observed in elderly, white-skinned males
    in Queensland, Australia, and Texas, USA. Populations with
    constitutionally, heavily pigmented skin run only a minimum risk of
    developing skin cancer in their lifetime.


        The development of criteria for both upper and lower limits of
    exposure to either natural or artificial UVR is extremely difficult
    because of such problems as:

         (a) the variation in both the acute and chronic effects of UVR
    of different wave lengths;

         (b) the considerable differences in the spectral composition of
    light from different sources and particularly of sunlight at different

         (c) the great differences in cutaneous sensitivity to UVR due
    to genetic, environmental, and adaptive effects, and the considerable
    variation in sensitivity in the same person at different times; and

         (d) the difficulty of differentiating between the necessary
    dose of UVR compatible with the upkeep of life, and the lowest dose
    that results in serious detrimental effects.

    7.1  Range of Exposure Limits

    7.1.1  Exposure to solar ultraviolet radiation

        As described in section 6, two thirds of the daily amount of
    solar UV-B radiation reaches the earth between 10h00 and 14h00. Thus,
    exposure should be reduced to a miminum during these hours. After a
    period of acclimatization, most people can tolerate several hours of
    outdoor exposure in the morning and afternoon, but shielding in the
    near noon hours should always be considered. In general, exposure
    during this very important period of acclimatization should not exceed
    4 minimal erythema doses per day without some protection (either
    clothing or sunscreens, section 7.3). This would correspond to 1 h of
    exposure in the tropics. A dose of 1/8 MED per day appears to be
    sufficient to prevent UVR deficiency.

    7.1.2  Occupational exposure to artificial ultraviolet radiation

        No internationally agreed limits exist at this time for
    occupational exposure to UVR, which take into consideration the acute
    effects and the risk of late cancer development. So far, the only
    limits available, which could be used in the preparation of
    guidelines, have been proposed by the National Institute of
    Occupational Safety and Health in the USA (NIOSH, 1975).

        The limits are based on the minimal erythema dose (MED) and the
    minimal photokeratitic dose, which means that only acute effects have
    been taken into consideration. For the UVR 200-315 nm region, it is
    stated that radiant exposure in any 8-h period must not exceed the
    values given in Table 11. For the wavelength range 315-400 nm, the
    total irradiance on unprotected skin or eye must not exceed 10 W/m2
    for periods exceeding 103 seconds. For radiant exposure of shorter
    durations, it should not exceed 10 000 J/m2. The limit for 315-400 nm
    is probably much too low and could be revised to a higher level.

    Table 11.  Total permissible 8-h doses and relative spectral
               effectiveness of some selected monochromatic

     Wavelength    Permissible 8-h      Relative spectral
        (nm)         dose (J/m2)    effectiveness
                                        (S lambda)b

         200            1000                 0.03
         210             400                 0.075
         220             250                 0.12
         230             160                 0.19
         240             100                 0.30
         250              70                 0.43
         254              60                 0.50
         280              46                 0.65
         270              30                 1.00
         280              34                 0.88
         290              47                 0.84
         300             100                 0.30
         305             500                 0.06
         310            2000                 0.015
         315          10 000                 0.003

    a "From: NIOSH (1975).

    Table 12.  Maximum permissible exposure times for selected
               values of Ieffa

           Duration of exposure             Effective irradiance,
                  per day                       Ieff (W/m2)b

                     8 h                             1.0
                     4 h                             2.0
                     2 h                             4.0
                     1 h                             8.0
                    30 min                          17.0
                    15 min                          33.0
                    10 min                          50.0
                     5 min                         100.0
                     1 min                         500.0
                    30 sec                        1000.0

    a From: NIOSH (1975).
    b Effective irradiance = action spectrum weighted irradiance.

        However, these values only apply to sources emitting essentially
    monochromatic UVR. The maximum permissible exposure for a broad band
    source should be calculated by summing up the relative contributions
    from all its spectral components, each being weighted by the relative
    spectral effect SL, as given in Table 12. In addition, these
    guidelines for determining exposure limits should not be used for
    photosensitive individuals.

        So far, none of the guidelines has included an evaluation of the
    carcinogenic risk, as neither the action spectrum nor the
    dose-response curve is known for man. It is hoped that this will be
    obtained by comparison of cancer incidence and UV irradiance as
    measured by the Robertson-Berger method.

    7.1.3  Exposure of the general population to artificial ultraviolet

        The exposure of the general population to artificial UVR is
    primarily for hygienic and for cosmetic purposes. The use of UVR for
    health purposes is discussed in sections 7.2 and 7.3.

        The use of UVR for cosmetic purposes generally involves a
    requirement for the development of skin pigmentation. For this reason,
    it is unrealistic to follow the occupational standards, since they
    would not allow the desired effects to be obtained.

        Doses of UVR sufficient to produce slight erythema in 24 hours
    are usually adequate for cosmetic purposes. Significant overdoses and
    repeated UVR exposures for prolonged periods should be avoided. The
    eyes must be properly shielded during each exposure. The risk of the
    development of skin cancer due to chronic exposure to UVR for cosmetic
    purposes is not known.

        A number of devices available to the general population emit
    significant amounts of UVR, or will do so if the protective envelope
    of the device is damaged, and may cause acute UVR-induced eye and skin
    damage. Such devices include Wood's lights, sterilizing and
    ozone-producing lamps, and high power mercury and xenon arc lamps used
    for illumination.

    7.1.4  Measurement of natural and artificial ultraviolet radiation

        Measurement of solar UVR involves serious difficulties, because
    of the need for accurate spectral discrimination at the shortest end
    of the solar spectrum. This is necessary because of the considerable
    variations in the biological effectiveness of UVR shorter than 320 nm.
    Few really practical, accurate, stray light-free spectroradiometers
    have been developed so far, for use in the middle UVR region (UV-B)
    and the use of action spectrum weighted, integrating analogue UVR
    meters has been found to be much more practical.

        The few practical prototypes of integrating chemical UVR
    dosimeters that have been developed are still in the experimental
    stage. If they can be perfected, such personal UVR dosimeters would be
    of the greatest use (Challoner et al., 1976; Davis et al., 1976).

        Basically, the same problems pertain to monitoring of artificial
    UVR, although measurements are somewhat easier in a laboratory

        The exposure criteria recommended in section 7.1.2 have not been
    put to practical use, because it is still not technologically possible
    to measure UVR adequately for compliance.

        Thus, working practices are recommended for the control of
    exposure in situations where sufficient measurement or emission data
    are not available. A frequently practiced method of protection
    consists of adequate containement of UVR-producing light sources.

    7.2  Health Effects of Solar Ultraviolet Radiation in the General

        Two aspects of health protection in the general population are of
    interest. One is the prevention of UVR deficiency that can occur in
    populations living near the north and south poles (generally at
    latitudes of 60° or more). The other deals with the protection of
    pale-skinned people from excessive UVR in subtropical and tropical
    areas (generally between latitudes 35° N and 35° S).

        The zoning of the USSR for UVR is particularly interesting from a
    health point of view (Belinskij, 1971). In the "UVR-deficit zone" it
    appears essential to use irradiation from artificial sources, during
    certain months, to compensate for UVR deficiency. In the "UV comfort
    zone", artificial irradiation is unnecessary. In the "UVR excess
    zone", it is essential to undertake measures for protection against
    solar UVR, in order to avoid skin cancer. It has also been proposed
    that, in order to prevent skin tumours among town dwellers in whom
    light starvation has caused depigmentation of the skin, preventive UVR
    should be carried out to increase skin pigmentation.

    7.3  UVR Deficiency and its Prevention

    7.3.1  Insolation and UV irradiation of built-up areas

        It is well known that solar energy entering a room illuminates,
    warms, dries, and particularly important, disinfects it, thus having a
    beneficial, physical and psychological effect. The sanitation
    standards and regulations for the insolation of dwellings and public
    buildings and built-up areas, which are in force at present in the
    USSR, are based on the requirement that premises should receive three
    hours' uninterrupted insolation on cloudless days during the period 22
    March-22 September and that protection should be given to limit the
    thermal effect of solar radiation in the southern regions, below
    latitude 55°N (State Standards, 1976b).

        This health requirement is evident from a number of reviews
    (Dancig, 1971; Galanin & Pirkin, 1971; Aleksandrov et al., 1975).
    Solar UVR has a particularly valuable health-effect in that,  inter
     alia, it speeds up the processes of environmental selfpurification
    (Belikova, 1960; Gluscenko et al., 1975). Therefore, town planning
    tasks should include the rational use of UVR from the sun and sky
    (Davidson, 1970; Gusev & Dunaev, 1971).

        Since window glass cuts off the most biologically active
    component of natural UVR, research to increase the UVR transparency of
    window glass has been of particular concern to health workers in the
    most northern latitudes (Belikova, 1964).

    7.3.2  Sunbathing and air-bathing in the prevention of UVR deficiency

        In addition to measures ensuring the maximum possible penetration
    of natural UVR into working and dwelling places, prevention of UVR
    deficiency can also be ensured by organizing solaria, beaches, and
    sports areas attached to children's establishments (kindergartens and
    pioneer camps), and to factories and mills. A schedule for the UV
    irradiation of children and adults, for sun and sun-and-air baths at
    different geographical latitudes, at different seasons of the year,
    and at different times of the day has been developed (Generalov,
    1971). At present, the effects of such solar radiation schedules
    cannot be extrapolated to potential late effects.

    7.3.3  Artificial ultraviolet radiation in the prevention of UVR

        Effective principles for the use of artificial UVR in the
    prevention of UVR deficiency and "light starvation" in man have been
    developed in the USSR. The recommended levels consist of a daily dose
    of UV-B of between 0.125 and 0.75 of the threshold erytherna dose
    (State Standards, 1964). The use of prophylactic UV irradiation has
    been shown to be quite effective in workers in industries lacking
    natural light (Bocenkova, 1971) and particularly effective in children
    of preschool and school age (Ronge, 1948; Zilov, 1971).

        Regulations have been drawn up for the planning and operation of
    artificial UV irradiation devices in industrial enterprises (State
    Standards, 1976b).

    7.4  Protection against Ultraviolet Radiation

        The whole of the world population has a potential for developing
    skin cancer, the risk depending on the intensity and degree of
    exposure to solar UVR during the life span. If all current exposure to
    solar UVR could be significantly reduced, the incidence of skin cancer
    would eventually decrease greatly.

        Health and appearance can be adequately catered for by exposing
    only part of the body for less than half an hour per day at or near
    noon, except at latitudes north of 60° N.

    7.4.1  Sunscreen preparations

        Sunscreen preparations are usually classified as chemical or
    physical agents. The former include para-aminobenzoic acid and its
    esters, cinnamates, and benzophenones, all of which act by absorbing
    radiation, which is dissipated as radiation of lower energy. Physical
    agents act as simple physical barriers, reflecting, blocking, or
    scattering light. They include titanium dioxide, talc, and zinc oxide.
    Mainly because of cosmetic objections, the physical barriers are not
    often used in sunscreen formulations (Robertson, 1972).

        The principle of covering the skin by spreading a layer of
    reliable UV absorber on the surface has proved a popular one.
    Providing that the thickness of the layer applied is adequate and that
    it adheres to the skin, it gives protection to the wearer under all

        Details of the kind of chemicals and bases used are beyond the
    scope of this report.

    7.4.2  Clothing

        Covering the skin with clothing gives a sense of security that is
    often misleading. The most frequent sites for skin cancer are those
    that face upward. Thus, a hat is essential for adequate protection of
    the forehead, scalp, and tops of ears. However, generally, it gives
    only partial protection for the nose, less for the lower face, and
    none for the hands and arms.

        Body coverings worn in hot climates are generally not complete
    absorbers. The average white shirt worn by men may transmit 20% of
    UVR, while lighter weaves favoured by women may allow 50% of UVR to
    reach the shoulders. Fairly complete clothing cover is more tolerable
    in a dry atmosphere than a humid, coastal, tropical environment.

    7.4.3  Behavioural conformity with the environment

        When unexpectedly detained in the sun, protective procedures
    available include facing in a variety of directions, hanging the head
    and shielding the head with the hands or with a handkerchief. Shadows
    should be used whenever possible, including one's own shadow. When
    standing in the shadow of a building, only rays from about half the
    sky are received, that is, about one quarter of the harmful intensity
    of full daylight. This is certainly useful protection, but fair skin
    will still burn in about one hour; in three hours, a painful burn may
    be initiated, although the sufferer has not been in direct sunlight at

        The dominant factor in the daily erythemal exposure is the angle
    of the sun above the horizon. This varies with latitude and with time
    of year. Thus, maximum exposure occurs, when the sun is almost
    directly overhead. The simplest means of protection is to take shelter
    around the middle of the day, especially in the summer months.

        At least one third of the whole day's UVR exposure occurs in the
    hour before and the hour after noon; half the day's exposure, enough
    for a very disabling sunburn, occurs during the 3-hour period around
    noon. If shelter is taken between 10h00 and 14h00, only one third of
    the day's exposure remains. Outside the period from 9h00 to 15h00,
    only one sixth remains, permitting considerable outdoor activity even
    for subjects with the most sensitive skin types.

    7.4.4  Occupational protection

        With the exception of medically prescribed doses, exposure of
    both the eyes and skin to UVR should be kept to a minimum. In order to
    protect persons in the vicinity of artificial UVR, the following
    precautions are recommended:

         (a) Whenever possible, prevention of excessive exposure of the
    eyes and skin should be ensured by proper engineering design of
    UVR-emitting installations and suitable enclosures, so that any UVR is
    either adequately contained or sufficiently attenuated.

         (b) When, for justifiable reasons, such containment is not
    possible, protection should be afforded by providing close-fitting
    goggles and/or face shields accompanied, if necessary, by suitable
    UVR-opaque clothing and gloves to cover the skin.

         (c) Adequate and appropriate instruction should be given, to
    any person liable to be excessively exposed to UVR, concerning the
    hazards involved and the precautions to be observed to avoid excessive

         (d) For artificial UVR sources that do not emit significant
    visible light, a visible or audible warning signal may be required to
    show when the UVR is being emitted.

         (e) Powerful short wavelength UVR sources may generate ozone.
    This additional hazard should be avoided by providing either adequate
    ventilation or an adequate ozone removal system in the workplace.


    AITKEN, R. (1937) Ultraviolet radiation treatment of preeclamptic
         toxemia.  Br. J. Phys. Med., 12: 45-47.

    ALEKSANDROV, V. N. & ALEKSANDROVA, A. I. (1975) [The insolation and UV
         climate of housing in the far north.]  Gig. i Sanit. 5: 16 (in

    ANCHEV, N., POPOV, I., MONOV N., & OUZOUNOV, N. (1968) Spreading of
         malignant neoplasms in the People's Republic of Bulgaria.
          Neoplasma, 15: 451-468.

         (1975) [Artificial sources of UV radiation with biological
         effect.] In:  [The biological effect of UV radiation.] Moscow,
         Nauka, pp. 221-225 (in Russian).

    BACHEM, A. (1956) Ophthalmic ultraviolet action spectra.  Am. J.
          Ophthalmol., 41: 969-975.

    BAIN, J. & RUSCH, H. P. (1943) Carcinogenesis with ultraviolet
         radiation of wave length 2, 800-3, 400 A.  Cancer Res.,
         3: 425-430.

    BEARD, H. H., BOGGESS, T. S., & VON HAAM, E. (1936) Experimental
         production of malignant tumors in the albino rat by means of
         ultraviolet rays.  Am. J. Cancer, 27: 257-266.

    BELIKOVA, V. K. (1964) [Evaluation from the hygienic standpoint of
         experimental samples of a window glass for residential and public
         buildings.]  Gig. i. Sanit., 1: 21-28 (in Russian).

    BELIKOVA, V. K. (1966)  [Natural ultraviolet radiation and its
          bactericidal importance.] Moscow, Medicina, pp. 322-326 (in

    BELIKOVA, V. K., ZABALUEVA, A. P., & GALPERIN, E. L. (1975)
         [Evaluation from the standpoint of hygiene of the zoning of the
         territory of the U.S.S.R. in respect to UV radiation levels.] In:
          [The biological effects of UV radiation.] Moscow, Nauka, pp.
         161-165 (in Russian).

    BELINSKIJ, V. A. (1971) [Zoning of the territory of the USSR in
         respect to the natural UV radiation.] In:  [Meteorology and
          climatology.] Issue 2, Moscow, Publishing House of the Moscow
         Branch of the Geographical Society, (in Russian).

    BELINSKIJ, B. A. & ANDRIENKO, L. M. (1974) [A simplified radiation
         model of the atmosphere in the UV spectral region.] In:
          [Radiation, processes in the atmosphere and on the earth's
          surface.] Leningrad, Gidrometeoizdat, pp. 273-276, (in

    BELINSKIJ, V. A. & GARADZA, M.P. (1963) [Ultraviolet climate of the
         USSR.] In  [Proceedings of the All-Union Scientific
          Meteorological Meeting.] Leningrad, Gidrometeozidat,
         pp. 244-252 (in Russian).

    BELINSKIJ, V. A. & GARADZA, M.P. (1962) [Scattered UV-radiation in the
         Eastern Pamirs.] In:  [Scientific Communications of the Institute
          of Geology and Geography of the Academy of Sciences of the
          Lithuanian SSR.] Vilanus, Vil. XIII, pp. 283-287 (in Russian).

         (1968)  [Sun and sky ultraviolet radiation.] Moscow, Moscow
         University Press (in Russian).

    BENDER, M. A., GRIGGS, H. G., & WALKER, P. L. (1973) Mechanisms of
         chromosomal aberration production. I. Aberration induction by
         ultraviolet light.  Mutat. Res., 20: 387-402.

    BENER, P. (1972)  Approximate values of intensity of natural
          ultraviolet radiation for different amounts of atmospheric
         ozone. London, European Research Office, United States Army.
         (Contract DAJA 36-68-C-1017).

    BEN-HUR, E. & ELKIND, M. M. (1973) DNA cross-linking in Chinese
         hamster cells exposed to near ultraviolet light in the presence
         of 4,5',8-trimethylpsoralen.  Biochim. Biophys. Acta,
         331: 181-193.

    BERENBLUM, I. & SHUBIK, P. (1947) The role of croton oil applications,
         associated with a single painting of a carcinogen, in tumor
         induction of the mouse's skin.  Br. J. Cancer, 1: 379-382.

    BERENBLUM, I. & SHUBIK, P. (1949) An experimental study of the
         initiating stage of carcinogenesis, and a re-examination of the
         somatic cell mutation theory of cancer.  Br. J. Cancer,
         3: 109-118.

    BERGER, D., URBACH, F., & DAVIES, R. E. (1967) The action spectrum of
         erythema induced by ultraviolet radiation.  Proceedings of the
          13th International Congress of Dermatology, Berlin, Springer
         Verlag, pp. 1112-1117.

    BERGER, D., ROBERTSON, D. F. & DAVIES R. E. (1975) Field measurements
         of biologically effective UV radiation. In:  Impacts of climatic
          change on the biosphere, Springfield, VA, National Technical
         Information Service, Part I, Chapter 2, pp. 233-264 (Appendix D,
         CIAP Monograph No. 5).

    BEUKERS R. & BERENDS, W. (1960) Isolation and identification of the
         irradiation product of thymine.  Biochim. Biophys. Acta,
         41: 550-551.

    BILLEN, D. & GREEN, A. E. S. (1975) Comparison of germicidal activity
         of sunlight with the response of a sunburning ultraviolet meter.
         In:  Impacts of climatic change on the biosphere, Springfield,
         VA, National Technical Information Service, Part 1, Chapter 2,
         pp. 299-305 (Appendix F, CIAP Monograph No. 5).

    BISCHOFF, F. (1969) Carcinogenic effects of steroids. In: Paoletti, &
         Kritchevsky, ed.  Advances in lipid research. New York, Academic
         Press, Vol. 7, pp. 165-244.

    BLACK, H. S. & CHAN, J. T. (1976) Etiologic related studies of
         ultraviolet light-mediated carcinogenesis.  Oncology,
         33: 119-122.

    BLACK, H. S. & DOUGLAS, D. R. (1973) Formation of a carcinogen of
         natural origin in the etiology of UV-carcinogenesis.  Cancer
         Res., 33: 2094-2096.

    BLACK, H. S. & LO, W. B. (1971) Formation of a carcinogen in human
         skin irradiated with ultraviolet light.  Nature (Lond.),
         234: 306-308.

    BLACK, H. S., CHAN, J. T., & BROWN, G. E. (1978) Effects of dietary
         constituents on ultraviolet light-mediated carcinogenesis.
          Cancer  Res., 38: 1384-1387.

    BLUM, H. F. (1941) Sunlight and cancer of the skin.  J. Natl Cancer
          Inst., 1: 397-431.

    BLUM, H. F. (1943) Wavelength dependence of tumor induction by
         ultraviolet radiation.  J. Natl Cancer Inst., 3: 533-537.

    BLUM, H. F. (1969) Quantitative aspects of cancer induction by
         ultraviolet light: Including a revised model. In: Urbach, F., ed.
          The  biological effects of ultraviolet radiation, Oxford,
         Pergamon Press.

    BLUM, H. F. & LIPPINCOTT, S. W. (1943) Carcinogenic effectiveness of
         ultraviolet radiation of wavelength 2537A.  J. Natl Cancer Inst.,
         3: 211-216.

    BLUM, H. F., GRADY, H. G., & KIRBY-SMITH, J. S. (1943) Relationships
         between dosage and rate of tumor induction by ultraviolet
         radiation.  J. Natl Cancer Inst., 3: 91-97.

    BLUM, H. F., BUTLER, E. G., DAILEY, T. H. DAUBE, J. R., MAWE, R. C., &
         SOFFEN, G. W. (1959) Irradiation of mouse skin with single doses
         of ultraviolet light.  J. Natl Cancer Inst., 22: 979-993.

    BOCENKOVA, T. D. (1971) [The application of prophylactic
         UV-irradiation to workers in buildings of a new type.] In:
          [Ultraviolet radiation.] Moscow, Medicina, pp. 245-251 (in

         CIBIREVA, E. M, KOSTIN, N. F., & EMELKIN, V. I. (1975)
         [Continuous and pulsed ultraviolet irradiation in combined
         treatment of protracted and chronic pneumonia.] In:
          [The biological effect of UV-radiation.] Moscow, Nauka,
         pp. 126-127 (in Russian).

    BOVIE, W. T. & KLEIN, A. (1919) Sensitization to heat due to exposure
         to light of short wavelengths.  J. Gen. Physiol., 1: 331-336.

    BOYCE, R. P. & HOWARD-FLANDERS, P. (1964) Release of ultraviolet
         light-induced thymine dimers from DNA in  E. coli K-12.  Proc.
          Natl Acad. Sci., 51: 293-300.

    BRIDGES, B. A. & HUCKLE, J. (1970) Mutagenesis of cultured mammalian
         cells by X-radiation and ultraviolet light.  Mutat. Res.
         10: 141-151.

    BUCHANAN, A. R., HELM, H. C., & STILSON, D. W. (1960)  Biomedical
          effects of exposure to electromagnetic radiation.
          I. Ultraviolet. Dayton, OH, Wright-Patterson Air Force Base,
         pp. 60-376 (WADD Technical Report).

    BUSCHKE, W., FRIEDENWALD, J. S., & MOSES, S. G. (1945) Effects of
         ultraviolet irradiation on corneal epithelium: Mitosis, nuclear
         fragmentation, post-traumatic cell movements, loss of tissue
         cohesion.  J. Cell. Comp. Physiol., 26: 147-164.

    CAKLIN, A. V. (1974) [The epidemiology of malignant neoplasms.] In:
          [Handbook on oncology.] Moscow, Medicina, pp. 26-27 (in

    CARLSON, L. D. & JACKSON, B. H. (1959) Combined effects of ionizing
         radiation and high temperature on longevity of Sprague-Dawley
         rat.  Radiat. Res., 11: 509-519.

    CASTO, B.C. (1973) Enhancement of adenovirus transformation by
         treatment of hamster cells with ultraviolet irradiation, DNA base
         analogs, and dibenz(a,h,)anthracene.  Cancer Res., 33: 402-407.

         B. L., GUPTA, S. P., & MAGNUS, I. A. (1976) Personnel monitoring
         of exposure to ultraviolet radiation.  Clin. exp. Dermatol.,
         1: 175-179.

    CHANDRA, P. (1972) Photodynamic action: A valuable tool in molecular
         biology.  Res. org. biol. med. chem., 3 (1): 232-258.

         Nucleic acid modification by furocoumarins and light: Some
         biomedical implications. In: Jung, E., ed.  Photochemotherapie,
         Stuttgart, F. K. Schattauer Verlag, pp. 25-32.

    CHARLIER, M. & HELENE, C. (1972) Photochemical reactions of aromatic
         ketones with nucleic acids and their components I-. Purine and
         pyrimidine bases and nucleosides.  Photochem. Photobiol.,
         15: 71-87.

    CLEAVER, J. E. (1973)  Xeroderma pigmentosum- progress and regress.
          J. invest. Dermatol., 60: 374-380.

    CLEAVER, J. E. & THOMAS, G. H. (1969) Single-strand interruptions in
         DNA and the effects of caffeine in Chinese hamster cells
         irradiated with ultraviolet light.  Biochem. biophys. Res. Comm.
         26: 203-208.

    CLEAVER, J. E., THOMAS, G. H., TROSKO, J. E., & LETT, J. T. (1972)
         Excision repair (dimer excision, strand breakage and repair
         replication) in primary cultures of eukaryotic (bovine) cells.
          Exp.  cell Res., 74: 67-80.

    CLEAVER, J. E. & TROSKO, J. E. (1969) DNA-degradation productions from
         mammalian cells irradiated with ultraviolet light.  Int. J.
          radiat. Biol., 15: 411-424.

    COBLENTZ, W. W., STAIR, R., & HOGUE, J. M. (1932) The spectral
         erythemic reaction of the untanned human skin to UV radiation.
          Bur.  Stand. J. Res., 8: 541-547.

    COGAN, D. G. & KINSEY, V. E. (1946) Action spectrum of keratitis
         produced by ultraviolet radiation.  Arch. Ophthalmol.,
         35: 670-677.

    COHEN-BAZIRE, G. & STANIER, R. Y. (1958) Inhibition of carotenoid
         synthesis in photosynthetic bacteria.  Nature (Lond.),
         181: 250-252.

    COX, B. & GAME, J. (1974) Repair systems in Saccharomyces.  Mutat.
          Res., 26: 257-264.

    CURTIS, G. L. (1975) Initiation-promotion skin carcinogenesis and
         immunological competence.  Proc. Soc. Exp. Med., 150 (1):
         pp. 61-64.

    CUTCHIS, P. (1978) On the linkage of solar ultraviolet radiation to
         skin cancer. Washington, DC, Federal Aviation Administration,
         Office of Environmental Quality, pp. 1342 (Institute for Defense
         Analysis Paper).

    DANCIG, N.M. (1971) [Lighting hygiene and insolation of buildings and
         built up areas in towns.] In:  [Questions of housing hygiene and
         of  curative power and preventive medicine.] Moscow, A. N. Sysin
         Institute, pp. 13-19 (in Russian).

    DANCIG, I. N. (1974) [Dental caries and UV deficiency.]
          Stimatologija, 1: 11-13 (in Russian).

    DANCIG, N.M. (1975) [The hygienic basis for preventing light sarvation
         among ships' crews.] In:  [The biological effects of UV
          radiation.] Moscow, Nauka, pp. 168-171 (in Russian).

    DANCIG, N. M., ZABALNEVA, A. P., & PROKOPENKO, Ju.I. (1975) [The
         importance of the protective effect of UV radiation in the
         development of the tumoral process under experimental
         conditions.] In:  [The biological effects of UV radiation.]
         Moscow, Nauka, pp. 137-142 (in Russian).

    DANIELS, F. J., BROPHY, D., & LOWITS, W. C. (1961) Histochemical
         response of human skin following ultraviolet radiation.
          J. invest. Dermatol., 37: 351-357.

    DAVIDSON, B. M. (1970) Relative evaluation of the insolation resources
         of flats in a residential "microdistrict".  Svetotekhnika,
         7; 13-15.

    DAVIES, J. N. P., KNOWLDEN, J., & WILSON, B. A. (1965) Incidence rates
         of cancer in Kyandondo County, Uganda, 1954-1960.  J. Natl Cancer
          Inst., 35: 789-821.

    DAVIES, R. E., DODGE, H. A., & AUSTIN, W. A. (1972a) Carcinogenicity
         of DMBA under various light sources.  Proceedings of the IX
          Congress on Photobiology, pp. 247.

    DAVIES, R. E., DODGE, H. A., & DESCHIELDS, L. H. (1972b) Alteration of
         the carcinogenic activity of DMBA by light.  Proc. Am. Assoc.
          Cancer Res., 13: 14.

    DAVIS, A., DEANE, G. H., & DIFFEY, B. L. (1976) Possible dosimeter for
         ultraviolet radiation.  Nature (Lond.), 261: 169-170.

    DJORDJEVIC, B. & TOLMACH, L. J. (1967) Responses of synchronous
         populations of HeLa cells to ultraviolet irradiation at selected
         stages of the generation cycle.  Radiat. Res., 32: 327-346.

    DOLEZOVA, V. (1976) To the question of the geographic distribution of
         pterygium.  Rev. int. Trach., 53: 55-64.

    DULBECCO, R. (i949) Reactivation of ultraviolet inactivated
         bacteriophage by visible light.  Nature (Lond.), 163: 949-950.

    DUKE-ELDER, W. S. (1926) The pathological action of light upon the
         eye. I. Action of the outer eye: Photophthalmia.  Lancet,
         1: 1137-1141.

    EASTCOTT, D. F. (1962) Epidemiology of skin cancer in New Zealand. In:
         Urbach, F., ed.  The biology of cutaneous cancer, Washington,
         DC, US Government Printing Office, pp. 141-152 (Monograph No. 10,
         National Cancer Institute).

    EDENBERG, H. J. & HANAWALT, P. C. (1973) The timecourse of DNA repair
         replication in ultraviolet irradiated HeLa cells.  Biochim.
          Biophys. Acta, 324: 206-217.

    EISENSTARK, A. (1971) Mutagenic and lethal effects of visible and
         near-ultraviolet light on bacterial cells.  Advances in Genetics,
         16: 167-198.

    ELKIND, M. M. & WHITMORE, G. F. (1967)  The radiobiology of cultured
          mammalian cells, New York, Gordon & Breach.

    ELWOOD, J. M., LEE, J. A. H., WALTER, S. D., MO, T., & GREEN, A. E. S.
         (1974) Relationship of melanoma and other skin cancer mortality
         to latitude and ultraviolet radiation in the United States and
         Canada.  Int. J. Epidemiol. 3: 325-332.

    ELWOOD, J. M. & LEE, J. A. H. (1975) Recent data on the epidemiology
         of malignant melanoma.  Semin. Oncol., 2 (2): 149-154.

    EMMETT, E. A. (1973) Ultraviolet radiation as a cause of skin tumors.
          CRC Crit. Rev. Toxicol., 2: 211.

    EMMETT, E. A. (1977a) Phototoxic keratoconjunctivitis from coal tar
         pitch volatiles.  Science, 198: 841-842.

    EMMETT, E. A. (1977b) Phototoxicity occurring during the manufacture
         of ultraviolet cured ink.  Arch. Dermatol., 113: 770-775.

    EPSTEIN, J. H. (1965) Comparison of the carcinogenic and
         co-carcinogenic effects of ultraviolet light on hairless mice.
          J. Natl Cancer Inst., 34: 741-745.

    EPSTEIN, J. H. & EPSTEIN, W. L. (1963) A study of tumor types produced
         by ultraviolet light in hairless and hairy mice.  J. invest.
          Dermatol., 41: 463-473.

    EPSTEIN, J. H., EPSTEIN, W. L., & NAKAI, T. (1967) Production of
         melanomas from DMBA-induced «Blue Nevi» in hairless mice with
         ultraviolet light.  J. Natl Cancer Inst., 38: 18-22.

    EPSTEIN, H. J., FUKUYAMA, K., & DOBSON, R. (1969) Ultraviolet light
         carcinogenesis. In: Urbach, F., ed.  The biological effects of
          ultraviolet radiation, Oxford, Pergamon Press.

    EVERETT, M. A., YEARGERS, E., SAYRE, R. M., & OLSON, R. L. (1966)
         Penetration of epidermis by ultraviolet rays.  Photochem.
          Photobiol., 5: 533-542.

    FABRE, F. (1971) A UV-supersensitive mutant in the yeast
          Schizosaccharomyces pombe. Molec. Gen. Genet., 110: 134-143.

    FEARS, T. R., SCOTTO, J., & SCHNEIDERMAN, M. A. (1977) Mathematical
         models of age and ultraviolet effects on the incidence of skin
         cancer among whites in the United States.  Am. J. Epidemiol.,
         105: 420-427.

    FINDLAY, G. M. (1930) Cutaneous papillomata in the rat following
         exposure to ultraviolet light.  Lancet, pp. 1229-1231.

    FISHER, M. S. & KRIPKE, M. L. (1977) Systemic alteration induced in
         mice by ultraviolet light irradiation and its relationship to
         ultraviolet carcinogenesis.  Proc. Natl Acad. Sci., 74
         (4): 1688-1692.

         A. (1974)  Sunlight and Man, Tokyo, University of Tokyo Press.

    FORBES, P. D. (1978) Experimental UV photocarcinogenesis. In:
          International Conference on Ultraviolet Carcinogenesis.
         Washington, DC, US Government Printing Office pp. 31-38
         (Monograph No. 50, National Cancer Institute).

    FORBES, P. D. & URBACH, F. (1975) Experimental modification of
         photocarcinogenesis. I. Fluorescent whitening agents and
         short-wave UVR.  Food Cosmet. Toxicol., 13: 335-337.

    FORBES, P. D. & URBACH, F. (1975) Experimental modification of
         photocarcinogenesis. II. Fluorescent whitening agents and
         simulated solar UVR.  Food Cosmet. Toxicol., 13: 339-342.

    FORBES, P. D. & URBACH, F. (1975) Experimental modification of
         photo-carcinogenesis. III. Simulation of exposure to sunlight and
         fluorescent whitening Agents.  Food Cosmet. Toxicol.,
         13: 343-345.

    FORBES, P. D., DAVIES, R. E., & URBACH, F. (1976) Phototoxicity and
         photocarcinogenesis: Comparative effects of anthracene and
         8-methoxypsoralen in the skin of mice.  Food Cosmet. Toxicol.,
         14: 243.

    FORNACE, A. J., KOHN, K. W., & KANN, H. E. (1976) DNA single-strand
         breaks during repair of UV damage in human fibroblasts and
         abnormalities of repair in xeroderma pigmentosum.  Proc. Natl
          Acad. Sci., 73: 39-43.

    FORTNER, J. G., MAKY, A. G., & SCHRODT, G. R. (1961) Transplantable
         tumors of the Syrian (golden) hamster. I. Tumors of the
         alimentary tract, endocrine glands and melanomas.  Cancer Res.,
         6 (Part 2): 161-198.

    FOX, M. (1974) The effect of post-treatment with caffeine on survival
         and UV-induced mutation frequencies in Chinese hamster and mouse
         lymphoma cells  in vitro. Mutat. Res., 24: 187-204.

    FREEMAN, R. G. (1975) Data on the action spectrum for ultraviolet
         carcinogenesis.  J. Natl Cancer Inst., 55: 1119-1121.

    FREEMAN, R. G. & KNOX, J. M. (1964a) Ultraviolet-induced corneal
         tumors in different species and strains of animals.  J. invest.
          Dermatol., 43: 431-436.

    FREEMAN, R. G. & KNOX, J. M. (1964b) Influence of temperature on
         ultraviolet injury.  Arch. Dermatol., 89: 858-864.

    GABOVIC, R. E., MINH, A. A., & MOTUZKOV, I. N. (1975) [The effect of
         UV radiation on the body's level of tolerance to exposure to
         chemicals.]  Vestn. Akad. Med. Nauk., 3: 26-37 (in Russian).

    GALANIN, N. F. & PIRKIN, V. M. (1971) [The rational utilization of the
         sun's radiant energy with a view to preventing ultraviolet
         deficiency.] In:  [Ultraviolet Radiation.] Moscow, Medicina, pp.
         209-212 (in Russian).

    GARADZA, M.P. (1965) [The natural UV radiation regime as shown by the
         results of measurements at the Moscow State University
         Meteorological Observatory.] In:  [The climate of a big city.]
         Moscow, MGU Publishing House, pp. 186-195 (in Russian).

    GARADZA, M. P. (1967) [Direct UV-radiation at different times of
         year.] In:  [The radiation regime and precipitations in Moscow.]
         Moscow, MGU Publishing House, pp. 165-175 (in Russian).

    GARADZA, M. P. (1974) [Features of the inflow of UV-radiation under
         different cloud condition.] In:  [Radiation processes in the
          atmosphere and on the earth's surface.] Leningrad,
         Cidrometeoizdat, pp. 261-264 (in Russian).

    GARADZA, M. P. & NEZVAL', E. I. (1971) [The effect of atmospheric
         transparency and cloud on the UV-radiation regime.] In:
          [Ultraviolet radiation.] Moscow, Medicina, pp. 316-321 (in

    GAVRILOVA, L. I., DOJNIKOV, A. S., & KORCAGINA, T. N. (1975) [UV
         radiation from arc and intermittent xenon lamps.] In:
          [The biological effect of UV radiation] Moscow, Nauka, pp.
         226-229 (in Russian).

    GENERALOV, A. A. (1971) [The ultraviolet irradiation regime for
         children and adults taking sun-baths and light and air baths at
         various latitudes.] In:  [Ultraviolet radiation.] Moscow,
         Medicina, pp. 203-207 (in Russian).

    GLUSCENKO, A. G., ARTJUSENCO, I. S., & BARANOVA, M. A. (1975) [Health
         indicators for children of crèche age in the ultraviolet climatic
         conditions of Kiev.] In:  [The biological effects of ultraviolet
          radiation.] Moscow, Nauka, pp. 171-174 (in Russian).

    GORDON, D. & SILVERSTONE, H. (1976) Worldwide epidemiology of
         premalignant and malignant cutaneous lesions. In:  Cancer of the
          skin, Philadelphia, W. B. Saunders Co., pp. 405-434.

    GRADY, H. G., BLUM, H. F., & KIRBY-SMITH, J. S. (1943a) Types of
         tumors induced by ultraviolet radiation and factors influencing
         their relative incidence.  J. Natl Cancer Inst., 3: 371-378.

    GRADY, H. G., BLUM, H. F., & KIRBY-SMITH, J. S. (1943b) Pathology of
         tumors of the external ear in mice induced by ultraviolet
         radiation.  J. Natl Cancer Inst., 2: 269-275.

    GRAHAM, J. H. & HELWIG, E. B. (1965) In: Montagna, W. & Dobson, R. L.,
         ed.  Advances in biology of the skin, New York, Macmillan
         (Pergamon), Vol. II, pp. 277-327.

    GREEN, A. E. S., ed. (1960)  The middle ultraviolet: Its science and
          technology, New York, John Wiley and Sons, Inc.

    GREEN, A. E. S. & HEIDINGER, R. A. (1978) Models relating ultraviolet
         light and non-melanoma skin cancer incidence.  Photochem.
          Photobiol., 28: 283-291.

    GREEN, A. E. S., SAWADA, T., & SHETTLE, E. P. (1975) The middle
         ultraviolet reaching ground. In:  Impacts of climatic change on
          the biosphere. Part 1, Chapter 2, pp. 29-49 (CIAP Monograph
         No. 5).

    GREEN, A. E. S., FINDLEY, G. B., Jr, KLENK, K. F., WILSON, W. M., &
         MO, T. (1976) The ultraviolet dose dependence of non-melanoma
         skin cancer incidence. Photochem. Photobiol., 24: 353-362.

    GRIFFIN, A. C. (1959) Methoxsalen in ultraviolet carcinogenesis in the
         mouse.  J. Invest. Dermatol, 32: 367-372.

         L. (1955) The effect of visible light on the carcinogenicity of
         ultraviolet light.  Cancer Res., 15: 523.

    GRIGGS, H. C. & BENDER, M. A. (1973) Photoreactivation of ultraviolet
         induced chromosomal aberrations. Science, 179: 86-88.

    GROSSMAN, L. (1968) Studies on mutagenesis induced  in vitro.
          Photochem. Photobiol, 7: 727-735.

    GUSEV, N. M. & DUNAEV, B. A. (1971) [The utilization of ultraviolet
         radiation in building.] In:  [Ultraviolet radiation.] Moscow,
         Medicina, pp. 218-221 (in Russian).

    HAMILTON, L. (1973) The influence of the cell cycle on the radiation
         response of early embryos. In: Balls, M. & Billet, F. F., ed.
          The cell cycle in development and differentiation, Cambridge,
         Cambridge University Press, pp. 229-247.

    HAN, A. & SINCLAIR, W. K. (1969) Sensitivity of synchronized Chinese
         hamster cells to ultraviolet light.  Biophys. J., 9: 1171-1192.

    HAN, A., SINCLAIR, W. K., & YU, C. K. (1971) Ultraviolet-light-induced
         division delay in synchronized Chinese hamster cells.
          Biophys. J., 11: 540-549.

    HANAWALT, P. C. & SETLOW, R. B., ed. (1975)  Molecular mechanisms for
          repair of DNA, New York & London, Plenum Press, pp. 827.

    HARBER, L. C. & BAER, R. L. (1969) Classification and characteristics
         of photoallergy. In: Urbach, F., ed.  The biologic effects of
          ultraviolet radiation, Oxford, Pergamon Press, pp. 519-526.

    HARRISON, A. P. (1967) Survival of bacteria. Harmful effects of light,
         with some comparisons with other adverse physical agents.  Annual
          Rev. Microbiol., 21: 143-156.

    HAUSSER, K. W. & VAHLE, W. (1922) [The dependence of light induced
         erythema and pigment formation upon the frequency (or wavelength)
         of the inducing radiation.]  Strahlentherapia, 13: 41-71 (in

    HAUSSER, K. W. & VAHLE, W. (1927) [Sunburn and suntan.]  Wiss
          Veröffent. Siemens-Konzern, 6: 101 (in German).

    HAYNES, R. H. (1975) DNA repair and the genetic control of
         radio-sensitivity in yeast. In: Hanawalt, P. C. & Setlow, R. B.,
         ed.  Molecular mechanisms for repair of DNA, New York & London,
         Plenum Press, pp. 529-540.

    HÉLENE, C. & CHARLIER, M. (1971) Photosensitized reactions in nucleic
         acids. Photosensitized formation and splitting of pyrimidine
         dimers.  Biochimie, 53: (11-12): 1175-1180.

    HELLMAN, K. B., HAYNES, K. F., & BOCKSTAHLER, L. E. (1974)
         Radiation-enhanced survival of a human virus in normal and
         malignant rat cells (37788).  Proc. Soc. Exp. Biol. Med.,
         145: 255-262.

    HERLITZ, C. W., JUNDELL, I., & WAHLGREN, F. (1930) [Malignant tumours
         in white mice caused by ultraviolet irradiation.]  Acta Paediat.,
         10: 333-347 (in German).

    HEROLD, H. J. & BERNDT, H. (1968) Cancer incidence in the German
         Democratic Republic. Selected tables.  Neoplasma, 15: 517-522.

    HILL, R. H. (1958) A radiation-sensitive mutant of  E. coli. Biochim.
          Biophys. Acta, 30: 636-637.

    HILL, L. & EIDENOW, A. (1923) Biological action of light: I. The
         influence of temperature.  Proc. R. Soc. (Biol.), 95: 163-180.

    HOLMBERG, M. & JONASSON, J. (1974) Synergistic effect of X-ray and UV
         irradiation on the frequency of chromosome breakage in human
         lymphocytes.  Mutat. Res., 23: 213-221.

    HSIAO, D. (1975) Impacts of climatic change on the biosphere.
         Springfield, Virginia. National Technical Information Service
         (CIAP Monograph No. 5).

    HUANG, C. W. & GORDON, M.P. (1973) Formation of cyclobutane-type
         pyrimidine dimers in RNA by sunlight.  Int. J. radiat. Biol.,
         23: 527-529.

    HUEPER, W. C. (1941) Cutaneous neoplastic responses elicited by
         ultraviolet rays in hairless rats and in their haired litter
         mates.  Cancer Res., 1: 402-406.

    HUTCHINSON, F. (1973) The lesions produced by ultraviolet light in DNA
         containing 5-bromouracil.  Quart. Rev. Biophys. 6: 201-246.

    IKUSHIMA, T. & WOLFF, S. (1974) UV-induced chromatid aberrations in
         cultured Chinese Hamster cells after one, two or three rounds of
         DNA replication.  Mutat. Res., 22: 193-201.

    IPPEN, H. (1969) Mechanisms of photopathological reactions. In:
         Urbach, F., ed.  The biologic effects of ultraviolet radiation,
         Oxford, Pergamon Press, pp. 513-518.

    JACOBSON, A. F. & YATVIN, M. B. (1976) Changes in the phospholipid
         composition of  E. coli following X and UV-irradiation.  Radiat.
          Res., 66: 247-266.

    JAGGER, J. (1967)  Introduction to research in ultraviolet
          photobiology, Englewood Cliffs, N J, Prentice-Hall, Inc.,
         pp. 164.

    JAGGER, J. (1969) Photoreactivation. In: Hollaender, A., ed.
          Radiation protection and recovery, New York, Pergamon Press,
         pp. 352-377.

    JAGGER, J. (1976) Effects of near-ultraviolet radiation on
         microorganisms.  Photochem. Photobiol., 23: 451-454.

    JESSUP, J. M., HANNA, N., PALASZYNSKI, E., & KRIPKE, M. L. (1978)
         Mechanisms of depressed reactivity to dinitrochlorobenzene and
         ultraviolet-induced tumours during ultraviolet carcinogenesis in
         BALB/c mice.  Cell. Immunol., 38: 105-115.

    JOHNSON, B. E. (1968) Ultraviolet radiation and lysosomes in skin.
          Nature (Lond.), 219: 1258-1259.

    JOHNSON, B. E., DANIELS, F., & MAGNUS, I. A. (1968) Response of human
         skin to ultraviolet light. In: Giese, A. C., ed.
          Photophysiology, New York, Academic Press, Vol. IV.

    JUNG, E. G. (1976)  [Photochemotherapy, background, techniques and
          complications.] Stuttgart -- New York, F. K. Schattaver Verlag
         (in German).

    JUNG, E. G., BOHNERT, E., & ERBS, G. (1971) Wavelength dependence of
         UV-induced alterations of epidermal cells in hairless albino
         mice.  Arch. Derm. Forsch., 241: 284-291.

    KAMENECKAJA, T. M. & MITROFANOVA, G. F. (1975) [The condition of
         certain neurohumoral regulatory systems following UV radiation at
         different wavelengths.] In:  [The biological effects of UV
          radiation.] Moscow, Nauka, (in Russian).

    KAO, F. & PUCK, T. T. (1969) Genetics of somatic mammalian cells. IX.
         Quantitation of mutagenesis by physical and chemical agents.
          J. Cell. Physiol., 74: 245-248.

    KARACEVCEVA, T. V. (1971) [The role on UV radiation as part of modern
         methods of treating and preventing rheumatism in children.] In:
          [Ultraviolet radiation.] Moscow, Medicina, pp. 154-158 (in

    KELNER, A. (1949) Photoreactivation of ultraviolet-irradiated
          Escherichia coli with special reference to close-reduction
         principle and to ultraviolet-induced mutation.  J. Bacteriol.,
         58: 511-522.

    KELNER, A. (1953) Growth, respiration, and nucleic acid synthesis in
         ultraviolet-irradiated and in photoreactivated E. coli.
          J. Bacteriol., 65: 252-262.

    KELNER, A. & TAFT, E. B. (1956) The influence of photoreactivating
         light on the type and frequence of tumors induced by ultraviolet
         radiation.  Cancer Res., 16: 860-866.

    KIEFER, J. (1971) The importance of cellular energy metabolism for the
         sparing effect of dose fractionation witch electrons and
         ultraviolet light.  Int. J. radiat. Biol., 20: 325-336.

    KIRBY-SMITH, J. S., BLUM, H. F., & GRADY, H. G. (1942) Penetration of
         ultraviolet radiation into skin, as a factor in carcinogenesis.
          J. Natl Cancer Inst., 2: 403-412.

    KOCH, H. R. (1967) [Photochemotherapy and cataract formation.]
          Dermatosen im Beruf und Umwelt., 26; 162-165 (in German).

    KOLLER, L. R. (1965)  Ultraviolet radiation, 2nd ed., New York, John
         Wiley and Sons.

         W., BARRETT, S. F., PETINGA, R. A., & BOOTSMA, D. (1975) Five
         complementation groups in xeroderma pigmentosum.  Mutat. Res.,
         33: 327-340.

    KRIPKE, M. L. (1974) Antigenicity of murine skin tumors induced by
         ultraviolet light.  J. Natl Cancer Inst., 53: 1333-1336.

    KRIPKE, M. L. (1976) Target organ for a systemic effect of ultraviolet
         radiation.  Photochem. Photobiol., 24: 599-600.

    KRIPKE, M. L. (1977) Latency, histology, and antigenicity of tumors
         induced by ultraviolet light in three inbred mouse strains.
          Cancer Res., 37: 1395-1400.

    KRIPKE, M. L. & FISHER, M. S. (1976) Effect of UV light on the host
         response to UV-induced tumirs.  Proceedings of the 4th Annual
          Meeting, American Society of Photobiology, Denver, CO, February

    KRIPKE, M. L. & FISHER, M. S. (1976) Immunologic parameters of
         ultraviolet carcinogenesis.  J. Natl Cancer Inst., 57: 211-215.

         S. (1977)  In vivo immune responses of mice during
         carcinogenesis by ultraviolet irradiation.  J. Natl Cancer Inst.,
         59: 1227-1230.

    LABORDUS, V. (1970) The effect of ultraviolet light on developing eggs
         of  Lymnaea stagnails (mollusca, pulmonata) I, II, III.  Proc.
          K. Ned. Akad. Wet. Amsterdam, C, 366-493.

    LAMOLA, A. A. & YAMANE, T. (1967) Sensitized photodimerization of
         thymine in DNA.  Proc. Natl Acad. Sci., 58: 443-446.

    LANCASTER, H. O. (1956) Some geographical aspects of the mortality
         from melanoma in Europeans.  Med. J. Aust., 1: 1082-1087.

    LATARJET, R. (1972) Interaction of radiation energy with nucleic
         acids.  Curr. Top. Radiat. Res. Q., 8: 1-38.

    LATARJET, R. & ZAJDELA, F. (1974) Effet inhibitcur de la caféine sur
         l'induction de cancers cutanés par les rayons ultraviolet chez la
         souris.  C. R. Acad. Sci. (Paris), 277: 1073-1076.

    LAZAREV, D. N. & SOKOLOV, M. V. (1971) [The measurement of ultraviolet
         radiation in units of effect.] In:  [UV Radiation.] Moscow,
         Medicina, pp. 328-333 (in Russian).

    LAZAREV, D. N. & SOKOLOV, M. V. (1974)  [Ultraviolet radiation.
          Quantities and units. Terms and definitions. Technical
          material for guidance.] Puscino, Institute of Biophysics of
         the Academy of Sciences of the USSR, pp. 1-8 (in Russian).

         (1975) [A UV biological photometer.] In:  [The biological effects
          of UV radiation.] Moscow, Nauka, pp. 244-246 (in Russian).

    LEE, J. A. H. & MERRILL, J. M. (1970) Sunlight and the aetiology of
         malignant melanoma: A Synthesis.  Med. J. Aust., 2: 840-841.

    LEE, H. H. & PUCK, T. T. (1960) The action of ultraviolet radiation on
         mammalian cells as studied by single-cell technique.  Radiat.
          Res., 12: 340-348.

    LEHMANN, A. R. (1972) Postreplication repair of DNA in
         ultraviolet-irradiated mammalian cells.  Mol. Biol.,
         66: 319-337.

         P. H. M., WEERD-KASTELEIN de, E. A., & BOOTSMA, D. (1975)
         Xeroderma pigmentosum cells with normal levels of excision repair
         have a defect in DNA synthesis after UV irradiation.  Proc. Natl
          Acad. Sci., 72: 219-223.

    LEWIS, N. F. & KUMTA, U.S. (1972) Evidence for extreme UV resistance
         of Micrococcus sp. NCTC 10785.  Biochem. biophys. Res. Commun.,
         47: 1100-1105.

    LIPSON, R. L. & BALDES, E. J. (1960) Photosensitivity and heat.  Arch.
          Dermatol., 82: 517-520.

    LOOMIS, W. F. (1970) Rickets.  Sci. Am., 233: 76-91.

    LUKIESH, M., HOLLADAY, L. L., & TAYLOR, A. H. (1939) Erythemal and
         tanning effectiveness of UV energy.  Gen. Electr. Rev.,
         42: 274-278.

    LYTLE, C. D. (1971) Host-cell reactivation in mammalian cells. I.
         Survival or ultraviolet-irradiated herpes virus in different
         cell-lines.  Int. J. radiat. Biol., 19: 329-337.

    LYTLE, C. D., HELLMAN, K. B., & TELLES, N. C. (1970) Enhancement of
         viral transformation by ultraviolet light.  Int. J. radiat.
          Biol., 18: 397-300.

    MACDONALD, E. J. (1976) Epidemiology of skin cancer 1975. In:
          Neoplasms of the skin and malignant melanoma, Chicago, Year
         Book Publishers, Inc., pp. 27-42.

    MACKIE, B. S. & MCGOVERN, V. J. (1958) The mechanism of solar
         carcinogenesis: A study of the role of collagen degeneration of
         the dermis in the production of skin cancer.  Arch. Dermatol.
          Syph., 78: 218-244.

    MAGNUS, I. A. & JOHNSON, B. E. (1965) Cited by Johnson, B. E.,
         Daniels, F. Jr, & Magnus, I. A. In: Giese, A. C., ed.
          Photophysiology, New York, Academic Press, Vol. IV,
         pp. 139-202.

    MAGNUS, K. (1973) Incidence of malignant melanoma of the skin in
         Norway, 1955-1970.  Cancer, 32: 1275-1286.

    MAGNUS, K. (1977) Incidence of malignant melanoma of the skin in the
         five nordic countries: significance of solar radiation.  Int. J.
          Cancer, 20: 477-485.

         (1974) Superficial cancer in the Sudan. A study of 1225 primary
         malignant superficial tumours,  Br. J. Cancer, 30: 355-364.

    MATHEWS, M. M. & KRINSKY, N. (1965) The relationship between
         carotenoid pigments and resistance to radiation in
         non-photosynthetic bacteria.  Photochem. Photobiol., 4: 813-817.

    MCGOVERN, V. J. (1977) Epidemiological aspects of melanoma: A review.
          Pathology, 9: 233-241.

    MCGOVERN, V. J. & MACKIE, B. S. (1959) The relationship of solar
         radiation to melanoblastoma.  Aust. N. Z. J. Surg., 28: 257-262.

    MEYER, A. E. H. & SEITZ, E. O. (1949)  [Ultraviolet Radiation.]
         Berlin, Walter de Gruyter & Co. (in German).

    MILLS, L. F., LYTLE, C. D., ANDERSEN, F. A., HELLMAN, K. B., &
         BOCKSTAHLER, L. H. (1975)  A review of biological effects and
          potential risks associated with ultraviolet radiation as used in
          dentistry. pp. 1-27 (DHEW Publication (FDA) 76-8021).

    MISHIMA, Y. & WIDLAN, S. (1967) Enzymatically active and inactive
         melanocyte populations and ultraviolet irradiation: Combined
         dopapremelanin reaction and electron microscopy.  J. invest.
          Dermatol., 49: 273.

    MIYAJI, T. (1962) Skin cancer in Japan. A nationwide 5 year survey.
         In: Urbach, F., ed.  The biology of cutaneous cancer,
         Washington, DC, US Government Printing Office, pp. 515-70
         (Monograph No. 10, National Cancer Institute).

         Influence of ultraviolet light on pigmentation of hairless mouse
         epidermis.  Jap. J. Dermatol., Ser. B, 78: 605.

    MORENO, F. (1969) Contribution à l'étude de la létalité et de la
         stérilité induites chez  Drosophita melanogaster par irradiation
         UV des cellules polaires de l'oeuf. I. Action létale, II. Action
         stérilisante.  Int. J. radiat. Biol., 16: 441-465.

    MOUSTACCHI, E., WATERS, R., HEUDE, M., & CHANET, R. (1975 The present
         status of DNA repair mechanisms in UV irradiated yeast taken as a
         model eukaryotic system. In: Nygaard, O., Adler, H., & Sinclair,
         W., ed.  Radiation research: Biomedical, chemical and physical
          perspectives, New York, Academic Press, pp. 632-650.

    MOVSHOVITZ, M. & MODAN, B. (1973) Role of sun exposure in the etiology
         of malignant melanoma: Epidemiologic inference.  J. Natl Cancer
          Inst., 51: 777-779.

    MULAY, D. M. (1962) Skin Cancer in India. In: Urbach, F., ed.
          The biology of cutaneous Cancer, Washington, DC, US Government
         Printing Office, pp. 215-224 (Monograph No. 10, National Cancer

    MURPHY, T. M. (1975a) Inactivation of tobacco mosaic virus ribonucleic
         acid by near- and middle-ultraviolet light: Sensitization by
         sulfanilamide and chlortetracycline.  Biochem. biophys. Res.
          Commun., 65: 1108-1114.

    MURPHY, T. M. (1975b) Effects of UV-B radiation on nucleic acids. In:
          Impacts of climatic changes on the biosphere, pp. 19-40 (CIAP
         Monograph No. 5).

         S., BORDIN, F., BACCICHETTI, F., & BEVILACQUA, R. (1974)
         Photoreactions between skin-photosensitizing furocoumarins and
         nucleic acids. In: Fitzpatrick, T. B., Pathak, M. A., Harber, L.
         C., Seiji, M., & Kukita, A., ed.  Sunlight and Man, Tokyo,
         University of Tokyo Press, pp. 369-387.

    NAKAMURA, K. & JOHNSON, W. C. (1968) Ultraviolet light-induced
         connective tissues changes in rat skin: A histopathologic and
         histochemical study.  J. invest. Dermatol., 51: 253-258.

    NATHANSON, R. B., FORBES, P. D., & URBACH, F. (1973) UV
         photocarcinogenesis: Modification by anti-lymphocytic serum or
         6-marcaptopurine.  Proc. Am. Assoc. Cancer Res., 14: 46
         (Abstract 182).

    NATHANSON, R. B., FORBES, P. D., & URBACH, F. (1976) Modification of
         photocarcinogenesis by two immunosuppressive agents.  Cancer
          Lett., 1: 243-247.

    NILENDER, R. A. & GAVANIN, V. A. (1971) [Artificial sources of
         ultraviolet radiation.] In:  [UV Radiation.] Moscow, Medicina,
         pp. 348-352 (in Russian).

    NIOSH (1975)  Ultraviolet transfer standard detectors and evaluation
          and calibration of NIOSH UV hazard monitor. Cincinnati, OH, US
         Department of Health, Education, and Welfare, Public Health
         Service, Center for Disease Control, National Institute for
         Occupational Safety and

    Health, Division of Laboratories and Criteria Development, 12 pp. (HEW
         Publication No. (NIOSH) 75-131).

    NORBURY, K. C., KRIPKE, M. L., & BUDMEN, M. B. (1977)  In vitro
         reactivity of macrophages and lymphocytes from
         ultraviolet-irradiated mice.  J. Natl Cancer Inst.,
         59: 1231-1235.

    OETTLE, A. G. (1962) Skin cancer in Africa. In: Urbach, F, ed.
          The biology of cutaneous cancer, Washington, DC, US Government
         Printing Office, pp. 197-214 (Monograph No. 10, National Cancer

    ORR, J. W. (1938) The changes antecedent to tumor formation during the
         treatment of mouse skin with carcinogenic hydrocarbons.
          J. Pathol. Bacteriol., 46: 495-515.

    OWENS, D. W., KNOX, J. M., HUDSON, H. T., RUDOLPH, A. H., & TROLL, D.
         (1977) Influence of wind on chronic ultraviolet light-induced
         carcinogenesis.  Br. J. Dermatol., 97: 285.

    PAINTER, R. B. (1975) Repair in mammalian cells: Overview. In:
         Hanawalt, P. C. & Setlow, R. B., ed.  Molecular mechamisms for
          repair of DNA, New York & London, Plenum Press, pp. 595-600.

    PARRINGTON, J. M. (1972) Ultraviolet-induced chromosome aberration and
         mitotic delay in human fibroblast cells.  Cytogenetics,
         11: 117-131.

         (1974) Photochemotherapy of psoriasis with oral methoxsalen and
         long wave ultraviolet light.  New Engl. J. Med. 291: 1207-1212.

    PATHAK, M. A., KRAMER, D. M., & FITZPATRICK, T. B. (1974) Photobiology
         and photochemistry of furocoumarins (psoralens). In: Fitzpatrick,
         T. B., Pathak, M. A., Harber, L. C., Seiji, M., & Kukita, A., ed.
          Sunlight and Man, Tokyo, University of Tokyo Press,
         pp. 335-368.

    PETTIJOHN, D. & HANAWALT, P. (1964) Evidence for repair-replication of
         ultraviolet damaged DNA in bacteria.  J. mol. Biol., 9: 395-410.

    PITTS, D. G. (1970) A comparative study of the effects of ultraviolet
         radiation on the eye.  Am. J. Optom., 47: 535-546.

    PITTS, D. G. & CULLEN, A. P. (1977)  Ocular ultraviolet effects from
          300 nm to 400 nm: A preliminary report. Cincinatti, OH, US
         Department of Health, Education and Welfare, National Institute
         of Occupational Safety and Health, Division of Biomedical and
         Behavioral Science (NIOSH Contract CDC-99-74-12).

    PITTS, D. G. & KAY, K. R. (1969) The photo-ophthalmic threshold for
         the rabbit.  Am. J. Optom., 46: 561-572.

    POLLARD, E. C. (1974) Cellular and molecular effects of solar
         ultraviolet radiation.  Photochem. Photobiol., 20: 301-308.

    PROKOPENKO, Ju, I. (1976) [Some data on the mechanisms of protective
         effect of UV-radiation.]  Gig. i Sanit., 1: 100-102 (in

    PROKOPENKO, Ju, I. & ZABALUEVA, A. P. (1975) [Activation of
         sanogenesis mechanisms with the help of UV-irradiation.] In:
          [The biological effect of UV-radiation,] Moscow, Nauka,
         pp. 156-159 (in Russian).

    PUTSCHAR, W. & HOLTZ, F. (1930) [Induction of skin cancer in rats by
         prolonged ultraviolet irradiation.]  Z. Krebsforsch.,
         23: 219-232 (in German).

    QUEVEDO, W. C. Jr & SMITH, J. A. (1963) Studies on radiation-induced
         tanning of skin.  Ann. N. Y. Acad. Sci., 100: 364.

    QUEVEDO, W. C. Jr, BRENNER, R. M., & KECHIJIAN, P. (1963) Melanocyte
         performance during radiation induced tanning of murine skin.
         Proceedings of the XVI International Congress on Zoology, 2: 306.

    QUEVEDO, W. C. Jr, SZABO, G., VIRKS, J., & SINESI, S. J. (1965)
         Melanocyte populations in UV-irradiated human skin.  J. invest.
          Dermatol., 45: 295.

    RADMAN, M. (1975) SOS repair hypothesis: Phenomenology of an inducible
         DNA repair which is accompanied by mutagenesis. In: Hanawalt, P.
         C. & Setlow, R. B., ed.  Molecular mechanisms for repair of DNA,
         New York & London, Plenum Press, pp. 355-367.

    RAPPAPORT, H., PIETRA, G., & SHUBIK, P. (1961) The induction of
         melanotic tumors resembling cellular blue nevi in the Syrian
         white hamster by cutaneous application of 7,
         12-Dimethylbenz(a)anthracene.  Cancer Res., 21: 661-666.

    RASMUSSEN, R. E. & PAINTER, R. B. (1964) Evidence for repair of
         ultraviolet damaged deoxyribonucleic acid in cultured mammal
         cells.  Nature (Lond.), 203: 1360-1362.

    RAUTH, A. M. (1970) Effects of ultraviolet light on mammalian cells in
         culture.  Curr. Top. radiat. Res., 6: 195-248.

    RAUTH, A. M. & DOMON, M. (1973) Potentiation of ultraviolet light
         damage in mouse L cells by 1-cyclohexyl-3-(2-morpholinyl-4-et
         carbodiimide metho-p-toluene sulphonate (CMEC).  Int. J. radiat.
          Biol., 24: 189-198.

    RESNICK, M. A. (1969) Genetic control of radiation sensitivity in
          Saccharomyces cerevisiae. Genetics, 62: 519-531.

    REYNOLDS, J. (1954) The epidermal melanocytes of mice.  J. Anat.,
         88: 45.

    ROBERTSON, D. F. (1969) Long term field measurements of erythemally
         effective natural ultraviolet radiation. In: Urbach, F., ed.
          The biologic effects of ultraviolet radiation, Pergamon
         Press, Oxford, pp. 433-436.

    ROBERTSON, D. F. (1972)  Solar ultraviolet radiation in relation to
          human sunburn and skin cancer. Thesis, Australia, University of

    ROBERTSON, D. F. (1975) Calculated sunburn responses, In:  Impacts of
          climatic change on the biosphere. Springfield, Virginia,
         National Technical Information Service, Part 1, Chapter 2,
         Appendix J. (CIAP Monograph 5).

    ROFFO, A. H. (1934) Cancer et soleil. Carcinomes et sarcomes provoqués
         par l'action du soleil  in toto. Bull. Assoc. Fr. Etud. Cancer,
         53: 59.

    ROMMELAERE, J., SUSSKIND, M., & ERRERA, M. (1973) Chromosome and
    chromatid exchanges in Chinese hamster cells.  Chromosoma,
         41: 243-257.

    RUNDEL, R. D. & NACHTWEY, D. S. (1978) Skin cancer and ultraviolet
         radiation.  Photochem. Photobiol., 28: 345-356.

    RONGE, H. E. (1948) Ultraviolet irradiation with artificial
         illumination  Acta Phys. Scand., 15 (Suppl. 49): 1-191.

    RUPERT, C. S. (1975) Enzymatic photoreactivation: Overview. In:
         Hanawalt, P. C. & SETLOW, R. B. ed.  Molecular mechanisms for
          repair of DNA, New York & London, Plenum Press, pp. 73-87.

    RUPP, W. D. & HOWARD-FLANDERS, P, (1968) Discontinuities in the DNA
         synthesized in an excision-defective strain of  E. coli
         following ultraviolet irradiation.  J. Mol. Biol., 31: 291-304.

    RUSCH, H. P., KLINE, B. E., & BAUMANN, C. A. (1941) Carcinogenesis by
         ultraviolet rays with reference to wavelength and energy.  Arch.
          Pathol., 371: 135-148.

    RUSCH, H. P., KLINE, B. E., & BAUMANN, C. A. (1942) Nonadditive effect
         of UV light and other carcinogenic procedures.  Cancer Res.,
          2: 183-188.

    RUSTAD, R. C. (1972) Techniques for the analysis of radiation-induced
         mitotic delay in synchronously dividing sea urchin eggs. In:
         Whitson, G. L., ed.  Concepts in radiation cell biology, New
         York & London, Academic Press, pp. 153-181.

    SAMS, W. M. Jr, SMITH, J. G., & BURK, P. G. (1964) The experimental
         production of elastosis with ultraviolet light.  J. invest.
         Dermatol., 43: 467.

    SATO, T. (1971) Pigmentation induced by ultraviolet irradiation in
         hairless mice with particular references to epidermal dendritic
         cells.  Jap. J. Dermatol. Ser. A, 81: 488.

    SATO, T. & KAWADA, A. (1972) Mitotic activity of hairless mouse
         epidermal melanocytes: Its role in the increase of melanocytes
         during ultraviolet radiation.  J. invest. Dermatol.,
         58: 392-395.

    SATO, T. & KAEADA, A. (1972) Uptake of tritiated thymidine by
         epidermal melanocytes of hairless mice during ultraviolet light
         radiation.  J. invest. Dermatol., 58: 71.

    SAUERBIER, W. (1976) UV damage at the transcriptional level.  Advances
          in radiation biology, 6: 50-106.

    SAYENKO, A. J. (1968) A method for studying morbidity from
         precancerous conditions and the question as to frequency of their
         occurrence on the territory of the Kirghiz Soviet Socialist
         Republic.  Neoplasma, 15: 565-571.

    SCHULZE, R. (1970) [Global Radiation Climate.]  Wiss. Forschungsber.,
         72: 220 pp. (in German).

    SCOTTO, J., KOPF, A. W., & URBACH, F. (1974) Non-melanoma skin cancer
         among Caucasians in four areas of the United States.  Cancer,
         34: 1333-1338.

    SCOTTO, J., FEARS, T. R., & GORI, G. B. (1976)  Measurements of
          ultraviolet radiation in the United States and comparisons with
          skin cancer data, National Cancer Institute (DHEW
         No. (NIH) 76-1029).

    SEIDL, E. (1969) Blitzgerät therapy. In: Urbach, F., ed.  The biologic
          effects of ultraviolet radiation, Oxford, Pergamon Press,
         pp. 663-672.

    SETLOW, R. B. (1968) The photochemistry, photobiology, and repair of
         polynucleotides.  Prog. N. A. Res. Mol. Biol., 8: 257-295.

    SETLOW, R. B. (1973) The relevance of photobiological repair.
          An. Acad. Bras. Ciencas, 45: 215-220.

    SETLOW, R. B. (1974) The wavelengths in sunlight effective in
         producing skin cancer: A theoretical analysis.  Proc. Natl Acad.
          Sci., 71: 3363-3366.

    SETLOW, R. B. & CARRIER, W. L. (1964) The disappearance of thymine
         dimers from DNA: An error-correcting mechanism.  Proc. Natl Acad.
          Sci., 51: 226-231. p. 34.

    SETLOW, J. K. & DUGGAN, D. E. (1964) The resistance of  Micrococcus
          radiodurans to ultraviolet radiation.  Biochim. Biophys. Acta,
         87: 664-668.

    SETLOW, J. K. & SETLOW, R. B. (1963) Nature of the photoreactivability
         ultraviolet lesion in deoxyribonucleic acid.  Nature (Lond.),
         197: 560-562. p 36.

    SHUBIK, P., PIETRA, G., & DELLA PORTA, G. (1960) Studies of skin
         carcinogenesis in the Syrian golden hamster.  Cancer Res.,
         20: 1.

    SILVERSTONE, H. & SEARLE, J. H. A. (1970) The epidemiology of skin
         cancer in Queensland: The influence of phenotype and environment.
          Br. J. Cancer, 24: 235-252.

    SKREB, Y., HORVAT, D., & EGER, M. (1972) Modifications of
         radiosensitivity in nucleate and anucleate amoeba fragments. In:
         Bonotto, S., Goutier, R., Kirchmann, R., & Maisin, J.-R., ed.
          Biology and radiobiology of anucleate systems I. New York,
         Academic Press, pp. 67-82.

    SMITH, K. C. (1974) The cellular repair of radiation damage. In:
         Fitzpatrick, T. B., Pathak, M. A., Harber, L. C., Seiji M., &
         Kukita, A., ed.  Sunlight and Man, Tokyo, University of Tokyo
         Press, pp. 67-77.

    SMITH, K. C. (1975) The radiation-induced addition of proteins and
         other molecules to nucleic acids. In: Wang, S. Y., ed.
          Photochemistry and photobiology of nucleic acids, New York,
         Academic Press, Vol. II, pp. 187-218.

    SMITH, K. C. & HANAWALT, P. C. (1969)  Molecular photobiology.
          Inactivation and recovery, New York & London, Academic Press.

    SOFFEN, G. A. & BLUM, H. F. (1961) Quantitative measurements of cell
         changes in mouse skin following a single dose of ultraviolet
         light.  J. cell. comp. Physiol., 58: 81-96.

    SOKOLOV, M. V. (1975) [Standardization of UV photometry.] In:
          [The biological effects of ultraviolet radiation.] Moscow,
         Nauka, pp. 232-235 (in Russian).

    SOKOLOV, M. V. (1976) [Topical questions of UV biophotometry.]
          Svetotecnika, 2: 20-22 (in Russian).

    SOZIN, D. S. (1975) [Low pressure fluorescent lamps with combined
         radiation.] In:  [The biological effects of ultraviolet
          radiation.] Moscow, Nauka, pp. 225-226 (in Russian).

    SPIKES, J. D., KRIPKE, M. L., CONNOR, R. J., & EICHWALD, E. J. (1977)
         Time of appearance and histology of tumors induced in the dorsal
         skin of C3Hf mice by ultraviolet radiation from a mercury arc
         lamp.  J. Natl Cancer Inst. 59: 1637-1643.

    STATE STANDARDS (1964)  [Recommendations for the prevention of
          ultraviolet deficiency.] Moscow Nauka, 50 pp. (in Russian).

    STATE STANDARDS (1976a) [Regulations for the design and operation of
         artificial UV-irradiation installations in industrial
         undertakings.] In: [Regulations on the design of electrical
         engineering installations for industry.]  Energija 6: pp. 30-39
         (in Russian).

    STATE STANDARDS (1976b)  [USSR building norms and regulations.]
         Strijizdat, Moscow, p. 20 (SNIP 11-60-75) (in Russian).

    STENBÄCK, F. (1969) Promotion in the morphogenesis of chemically
         inducible skin tumors.  Acta path. microbiol. Scand. Suppl.,
         208: 1-116.

    STENBÄCK, F. (1975a) Cellular injury and cell proliferation in skin
         carcinogenesis by UV light.  Oncology, : 31: 61-65.

    STENBÄCK, F. (1975b) Species-specific neoplastic progression by
         ultraviolet light on the skin of rats, guinea pigs, hamsters and
         mice.  Oncology, 31: 209-225.

    STENBÄCK, F. (1975) Ultraviolet light irradiation as initiating agent
         in skin tumor formation by the two-stage method.  Europ. J.
          Cancer, 11: 241-246.

    STENBÄCK, F. (1978) Life history and histopathology of ultraviolet
         light-induced skin tumors. In:  International Conference on
          Ultraviolet Carcinogenesis. Washington, DC, US Government
         Printing Office, pp. 57-70 (Monograph No. 50, National Cancer

    SUTHERLAND, B. M. (1974) Photoreactivating enzyme from human
         leukocytes.  Nature (Lond.), 109-112.

    SVIDERSKAJA, T. A. (1971) [Some experimental data on the conditions
         accompanying an intensification of blastomogenic effect.] In:
          [UV Radiation.] Moscow, Medicina, pp. 260-264 (in Russian).

    SWANBECK, G. & HILLSTRöM, L. (1971) Analysis of etiological factors of
         squamous cell skin cancer of different locations.  Acta
          Dermatovener, 51: 151-156.

    TALANOVA, I. K. & ZABALUEVA, A. P. (1972) [Evaluation of the extent to
         which children are provided with UV radiation in middle and
         northern latitudes.] In:  [Questions of experimental and clinical
          spa treatment and physiotherapy.] 20: 323-329 (in Russian).

    TALANOVA, I. K., KARACEVCEVA, T. V., & IVANOV, V. G. (1975) [The
         combination of physical methods of prophylaxis and specific
         immunization in children.] In:  [The biological effects of UV
          radiation.] Moscow, Nauka, pp. 116-120 (in Russian).

    TODD, P. & HAN, A. (1976) Ultraviolet light induced
         DNA-to-protein-cross-linking in mammalian cells. In: Smith, K.
         C., ed.  Aging, carcinogenesis and radiation-biology: The role of
          nucleic acid addition reactions, New York & London, Plenum
         Press, pp. 83-104.

    TROSKO, J. E. & CHU, E. H. (1973) Inhibition of repair of UV-damaged
         DNA by caffeine and mutation induction in Chinese hamster cells.
          Chem. Biol. Interactions, 6: 317-332.

    TYRRELL, R. M. (1973) Induction of pyrimidine dimers in bacterial DNA
         by 365 nm radiation  Photochem. Photobiol., 17: 69-73.

    URBACH, F. (1969)  The biologic effect of ultraviolet radiation.
         Oxford, Pergamon Press, pp. 704.

    URBACH, F., ROSE, D. B., & BONNEM, M. (1972) Genetic and environmental
         interactions in skin carcinogenesis. In:  Environment and skin
          cancer, Baltimore, Maryland, Williams & Wilkins Co.,
         pp. 355-371.

    VARGHESE, A. J. (1973) Properties of photoaddition products of thymine
         and cysteine.  Biochemistry, 12 (14): 2725-2730.

    VERHOEFF, F. H., BELL, L., & WALKER, C. B. (1916) The pathological
         effects of radiant energy on the eye: An experimental
         investigation with a systematic review of the (literature.  Proc.
          Am. Acad. Arts Sci., 51: 630-818.

    VITALIANO, P. P. (1978) The use of logistic regression for modelling
         risk factors in the development of nonmelanoma skin cancer.
          Am. J. Epidemiol., 108: 402-414.

    WANG, R. J. (1975) Lethal effect of »daylights» fluorescent light on
         human cells in tissue-culture medium.  Photochem. Photobiol.,
         21: 373-375.

    WANG, R. J., STOIEN, J. D., & LANDA, F. (1974) Lethal effect of
         near-ultraviolet irradiation on mammalian cells in culture.
          Nature (Lond.), 247: 43-45.

    WATERHOUSE, J., MUIR, C., CORREA, P., & POWELL, J. (1976)  Cancer
          incidence in five continents, Lyons, IARC (Vol. III).

    WHITSON, G. L. (1972) Radiation-induced biochemical changes in
         protozoa. In: Whitson, G. L., ed.  Concepts in radiation cell
          biology, New York, Academic Press, pp. 123-152.

    WINKELMAN, R. K., BALDES, E. J., & ZOLLMAN, P. E. (1960) Squamous cell
         tumors induced in hairless mice with ultraviolet light.
          J. invest. Dermatol., 34: 131-138.

    WINKELMANN, R. K., ZOLLMAN, P. E., & BALDES, E. J. (1965) Squamous
         cell carcinoma produced by ultraviolet light in hairless mice.
          J. invest. Dermatol., 40: 217-224.

    WITKIN, E. M. (1969) Ultraviolet-induced mutation and DNA repair.
          Ann. Rev. Genet., 3: 525-552.

    WITKIN, E. M. (1976) Ultraviolet mutagenesis and inducible DNA repair
         in  Escherichia coli. Bacteriol. Rev., 40: 869-907.

    WOODCOCK, A. & MAGNUS, I. A. (1976) The sunburn cell on mouse skin:
         Preliminary quantitative studies on its production.  Br. J.
          Dermatol., 95: 459-468.

    YEH, S. (1962) Relative incidence of skin cancer in Chinese in Taiwan:
         With special reference to arsenical cancer. In: Urbach, F., ed.
          The biology of cutaneous cancer, Washington, DC, US Government
         Printing Office, pp. 81-108 (Monograph No. 10, National Cancer

    ZACKHEIM, H. S. (1964) Comparative cutaneous carcinogenesis in the
         rat. Differential response to the application of anthramine,
         methylcholanthrene, and dimethylbenzanthacene.  Oncology,
         17: 236-246.

    ZIGMAN, S., SCHULTZ, J. B., & YULO, T. (1973) Possible roles of near
         UV light in the cataractous process.  Exp. eye Res.,
         15: 201-208.

    ZILOV, JU.D. (1971) [The prophylactic irradiation of children and
         adolscents living in different climatic zones of the Soviet
         Union.] In:  [Ultraviolet radiation.] Moscow, Medicina,
         pp. 237-241 (in Russian).

         (1975) [The UFM-meter and the UFB-72 laktmeter.] In:  [The
          biological effect of UV-radiation.] Moscow, Nauka, pp. 247-249
         (in Russian).

    ZWEIG, A. & HENDERSON, W. A. Jr (1976) A photochemical mid-ultraviolet
         dosimeter.  Photochem. Photobiol., 24: 543-549.

    See Also:
       Toxicological Abbreviations
       Ultraviolet radiation (EHC 160, 1994, 2nd edition)