The historical aspects of sunscreens.

While there is little literature on the way in which people protected themselves against the sun, evidence from paintings suggest that clothing covering the body, veils and large brim hats were used by ancient Greeks, and that umbrellas existed in ancient Egypt, Mesopotamia, China and India. Veiel in 1887 (Vierteljahresschr. Derm. Syph. 14, 113-116) was able to protect a patient with eczema solare by the use of a tightly woven red veil. In 1889, Widmark (Uber den Einfluss des Lichtes auf die Haut. Hygiea, Festband #3, Samson and Wallin, Stockholm) used acidified quinine sulfate to absorb UVB, apparently because, since quinine fluoresces when irradiated with UVR, he rightly assumed that it would absorb the short wavelengths. In 1891, Hammer (Uber den Enfluss des Lichtes auf die Haut, Ferdinand Enke, Stuttgart) repeated Widmark's experiments and used quinine prepared in lotion or ointment as the first human sunscreen. Various plant extracts had been used at the turn of the century in folk medicine. One of the most effective was a chestnut extract from which aesculin was derived. Unna (Med. Klinik. 1911;7:454-456) developed several glycosides of aesculin,which were introduced as Zeozon and Ultrazeozon. In 1922, Eder and Freund (Wiener. Klin. Wchnschr. 35, 681-684) introduced 2-naphthol-6,8-disulfonic acid salts (Antilux) which were quite effective in both the UVB and UVA region. Over the next 40 years a number of different chemicals were introduced for sunscreen purposes: tannic acid (1925), benzyl salicylate (1931), para-aminobenzoic acid derivatives and 2-phenylimidazole derivatives (1942), anthranilic acid (1950), various cinnamates (1954), chloroquine (1962), benzophenones (1965) and many more since then. The list of chemical useful for sunscreen formulation is now extensive, the US Food and Drug Administration and the European Community have published compendia of approved chemicals and inorganic filters.

Ultraviolet radiation and skin cancer of humans.

Current scientific evidence indicates that stratospheric ozone has declined worldwide over the past 20 years. The trend estimates are markedly dependent on the geographical location and are highly seasonal. Winter trends are much more negative than those for summer and autumn. Projections based on current assumptions of chlorine release suggest that this decline will continue into the next century. On the basis of the decrease in ozone over the mid-latitudes, an increase in biologically effective ultraviolet radiation (UVR) of 4%-9% is expected, depending on the season and geographical location. However, the UVR penetration to the Earth's surface is greatly affected by clouds, aerosols and tropospheric ozone, and current increases, if any, have not been as large as this. Direct evidence for the induction of non-melanoma skin cancer (NMSC) due to UVR has been derived from animal experiments in mice and rats. Numerous epidemiological data confirm that this relationship also holds for human skin. The increase in NMSC incidence in the past two decades is not likely to be due to the decrease in ozone, given the long latency (two to three decades) associated with UVR effects on skin. A knowledge of the action spectrum for NMSC development suggests that a 1% depletion in stratospheric ozone may be expected to increase NMSC, at equilibrium, by about 2.0% The evidence on the role of UVR exposure in the development of malignant melanoma (MM) is less certain. It has been estimated that a 1% reduction in ozone may cause an increase in MM of 0.6%.

Fluoroquinolone antibacterials enhance UVA-induced skin tumors.

Fluoroquinolone antibacterials are known to be phototoxic, both in vivo and in vitro. The action spectrum for the phototoxicity of the quinolones lies mainly in the UVA region. During studies of systemic drug phototoxicity, Johnson et al. (Dundee) induced dose-dependent phototoxicity in Swiss albino mice, and severe phototoxic reactions were followed by the development of skin tumors. The present study was designed to compare the ability of several quinolones to produce photobiologic effects following chronic, subphototoxic UVA radiation. To compare the activities of different quinolones (lomefloxacin, fleroxacin, ciprofloxacin, ofloxacin and nalidixic acid), doses that result in similar plasma and skin levels of drug were administered by gavage to slightly pigmented Skh-1 hairless mice for up to 78 weeks. 8-Methoxypsoralen (8-MOP) was used as a positive control, and unirradiated, drug-treated and irradiated and unirradiated drug-free controls were also used. No signs of phototoxicity were seen, except for minimal-to-slight erythema and swelling of the skin in animals of the lomefloxacin-UVA group. Skin tumors (1 mm in diameter or larger) were observed in all the irradiated groups and the incidence was increased in all the groups treated with the test articles. The cumulative tumor prevalence was accelerated, the median latent periods were shortened and tumor onset was significantly enhanced by 8-MOP plus UVA, lomefloxacin plus UVA and fleroxacin plus UVA, as compared with vehicle plus UVA-exposed animals. The majority of skin tumors (with the exception of lomefloxacin and 8-MOP) were benign. The majority of squamous cell carcinomas in the lomefloxacin group were of a histologic type different from those previously reported in UVA-exposed animals. Thus, all the fluoroquinolone antibiotics studied have the capability of enhancing UVA-induced phototumorigenesis, but only lomefloxacin caused the development of cystic squamous cell carcinomas in the majority of treated animals.

Ultraviolet radiation activates the human elastin promoter in transgenic mice: a novel in vivo and in vitro model of cutaneous photoaging.

The major alteration in photoaged skin is the deposition of massive amounts of abnormal elastic material, termed solar elastosis. In previous work, it has been shown that solar elastosis is accompanied by increased abundance of elastin and fibrillin mRNAs and upregulation of elastin promoter activity. Using a transgenic mouse line, which expresses the human elastin promoter, linked to a chloramphenicol acetyltransferase reporter gene, in a tissue-specific and developmentally regulated manner, we investigated the effects of ultraviolet A radiation and ultraviolet B radiation on human elastin promoter activity in vivo and in vitro. Irradiation of mice with a single dose of ultraviolet B radiation (491.4 mJ/cm2) resulted in an increase up to 8.5-fold in promoter activity, whereas a more modest increase of 1.8-fold was measured with ultraviolet A radiation (38.2 J/cm2). In addition, in vitro studies revealed over a thirtyfold increase in elastin promoter activity in response to ultraviolet B radiation (5.5 mJ/cm2), whereas no change was measured in response to ultraviolet A radiation (2.2 J/cm2). These results confirm the role of ultraviolet B radiation in elastin promoter activation in photoaging, and identify ultraviolet A radiation as a contributing factor. This system should serve as a useful in vivo and in vitro model to study cutaneous photoaging, and for testing compounds that may protect against cutaneous photodamage.

Ultraviolet A transmission by modern sunscreens: is there a real risk?

In recent years it has been realized that ultraviolet A (UVA) is capable of inducing many of the same deleterious events as UVB. In addition to erythema, UVA can cause connective tissue damage and is photocarcinogenic. Recently, concern has arisen that new, higher potency sunscreens allow dangerous amount of UVA to reach the skin, because they allow prolonged outdoor exposure. Such concerns are unfounded. The problem lies in a misunderstanding of the concept of sunlight protection factor. This is purely a multiplication factor and does not indicate that the effect of transmitted UVR is due to UVA or UVB. Action spectra show that UVA is less, but certainly not more injurious to skin than UVB. There is no reason to believe that higher potency sunscreens enhance exposure to dangerous amounts of UVA.

Potential health effects of climatic change: effects of increased ultraviolet radiation on man.

There is scientific evidence that stratospheric ozone concentration has declined over the Northern Hemisphere in the past 20 years, and projections based on various assumptions about future release of chlorofluorocarbon gases and other contaminants suggest that this decline will continue into the next century. The effects on human health secondary to increase in biologically effective ultraviolet radiation are expected to consist of increases in nonmelanoma skin cancer and malignant melanoma of the skin, possible alteration of immune response, and development of lens cataracts. The recent and projected increases in skin cancer and changes in human immune responses are discussed.

Evaluation of halobetasol propionate ointment in the treatment of plaque psoriasis: report on two double-blind, vehicle-controlled studies.

The results of two studies are presented that reveal the efficacy and safety of 0.05% halobetasol ointment in the treatment of patients with plaque psoriasis of at least moderate severity. Both multicenter studies were randomized, double-blind, and vehicle controlled, and study medications were applied twice daily for 2 weeks. One study was a paired-comparison (PC); the other study was of parallel-group (PG) design. Both studies called for evaluations at entry (week 0) and after 1 and 2 weeks of treatment. The PC study enrolled 100 patients; the PG study enrolled 110 patients; 204 patients provided efficacy data over both studies. In the PC study, plaque elevation, erythema, and scaling, at least moderately severe at entry, showed at the end of treatment both statistical (p less than or equal to 0.0003) and clinical significance (all greater than 1-unit difference on the rating scale) favoring 0.05% halobetasol ointment over vehicle. Pruritus (initially mild) and total score also showed statistically significant treatment differences favoring halobetasol at the final evaluation. Patient global responses for "effectiveness" and "overall rating" favored 0.05% halobetasol ointment over vehicle. In the PG study, induration, erythema, and scaling, at least moderately severe at entry, showed at the end of treatment both statistically and clinically significant differences favoring 0.05% halobetasol ointment over vehicle. Physician's global evaluation favored 0.05% halobetasol ointment over vehicle after 2 weeks of use. No patients were released from either study because of adverse events. No systemic adverse events or findings of skin atrophy were reported in these studies. Reports of "stings" or "burns" were equally divided between halobetasol and its vehicle.(ABSTRACT TRUNCATED AT 250 WORDS)

Incidence of nonmelanoma skin cancer.

Nonmelanoma skin cancers are the most common malignant neoplasms of fair-skinned people, in many sunny countries exceeding the total of all other neoplasms. The evidence that the primary causal agent is chronic repeated exposure to solar ultraviolet radiation is overwhelming. The incidence of basal cell carcinoma is always greater than that of squamous cell carcinoma, varying by latitude from 10:1 to 2.5:1. The incidence of nonmelanoma skin cancer has been increasing by 2% to 3% per year, at least in the United States. Most likely, this is caused by greater outdoor exposure for leisure and social reasons.

Potential effects of altered solar ultraviolet radiation on human skin cancer.

There is highly significant evidence that non-melanoma skin cancers are primarily due to chronic repeated exposure to solar ultraviolet radiation, and that there is a significant, although somewhat different relationship between solar radiation and the development of cutaneous malignant melanoma. Recent experimental and epidemiologic studies show that the biologically most effective UVR wavelengths are in the segment of the solar UVR spectrum that would be significantly augmented by decreases in stratospheric ozone content. A recent report on measurements of column ozone changes in the stratosphere has shown that in the past 18 yrs, there has been an ozone decrease between 2 and 3%, greater in the winter months, and somewhat differing with latitude in the Northern Hemisphere. Calculations of the relationship of ozone decrease to increase in biologically effective UVR show great dependence on the biologic action spectrum assumed. Based on extensive epidemiologic studies of skin cancer incidence, it appears that the estimated increase in biologically effective UVR due to the measured ozone decreases in the past (almost) two decades are not likely to be the cause of the sharp increase in skin cancer incidence which have been observed. Most likely these increases in incidence are the result of increasing personal exposure, due to striking changes in personal behavior that have taken place for social reasons. However, there is every reason to believe that increases in biologically effective UVR due to stratospheric ozone decreases will have significant impact on human skin cancer incidence in the future.

Testing the efficacy of sunscreens: effect of choice of source and spectral power distribution of ultraviolet radiation, and choice of endpoint.

The problems inherent in testing the protective efficacy of sunscreens are reviewed. Of primary importance are: the spectral power distribution of the test light source, which should simulate the ultraviolet radiation of midlatitude, midsummer sunlight; definition of minimal erythema of skin, and equilibration of light source and filters prior to testing.

Narrow-band UV radiation and induction of dermal elastosis and skin cancer.

A narrow-band UV light source with emission peaks at 292, 300, 307, 317, and 336 nm was developed and used to irradiate whole cages of hairless mice. The purpose was to obtain experimental information on the action spectrum for photocarcinogenesis and dermal elastosis. Groups of 20 mice were irradiated with 500 J/m2 daily, 5 times per week during one year. The total dose was 130 kJ/m2. All mice irradiated with 292 nm and 300 nm developed squamous cell carcinomas. None in the other groups developed malignant skin tumors. Elastosis was estimated quantitatively. The elastic fibers covered 3% of a representative microscopic section of dermis in the control group. In the groups irradiated with peaks at 336 nm, 317 nm, 307 nm, 300 nm, and 292 nm the corresponding percentages were 6%, 13%, 28%, 32%, and 36%, respectively. The shorter the wavelengths the more pronounced was a subepidermal zone replacing the elastotic tissue to the deeper dermis. This zone stained corresponding to a content of glycosaminoglycans (GAG), sulphated GAG, hyaluronic acid, mature collagen, and new reticulin.