J.C. van der Leun

Estimate of the wavelength dependency of ultraviolet carcinogenesis in humans and its relevance to the risk assessment of a stratospheric ozone depletion.

AbstractThe wavelength dependency of carcinogenesis is an important factor in risk assessments pertaining to sources of ultraviolet radiation, the most important of which is the sun. This wavelength dependency cannot be measured directly in humans, but it has been measured in hairless mice, and repr

TUMORIGENESIS BY A LONG WAVELENGTH UV-A SOURCE

Abstract— Albino hairless mice (Skh‐hrl) were exposed daily to radiation from a high‐power long wavelength UV‐A source (wavelengths longer than 340 nm). The irradiations lasted 2 h per day. The daily dose was 220 kJ/m2. Heavy scratching marks were observed in 13 out of 48 animals. However during the experiment 31 of the animals developed tumors of 1 mm or larger before any scratching was observed. The median induction time was 265 days for 1 mm tumors.

DOSE‐TIME DEPENDENCY OF TUMOR FORMATION BY CHRONIC UV EXPOSURE

‐An animal experiment is presented which involved a total of 223 albino hairless mice (Skh hr 1). These mice, excluding 24 of them which served as controls, were divided over 6 groups, each of which received a different but constant daily dose of UV radiation from fluorescent sunlamps (Westinghouse FS40TL12). The range of daily doses encompassed a factor of 33. Data on the response of each group as a whole are presented. The group responses are measured in two ways: (1) the proportion of tumor bearing mice (prevalence), and (2) the average number of tumors per survivor (yield). The data provide information on the variation of the group response with time, daily dose and tumor size.

Environmental effects of ozone depletion: 1998 assessment

The Montreal Protocol on Substances that Deplete the Ozone Layer requires periodic assessments of available scientific, environmental, technical and economic information. The assessments shall be made at least every four years. Assessments were made in 1989, 1991, 1994, and the present one, in 1998. The 1998 assessment focuses on new information since 1994, but it includes some background of prior information, so that it can be read without having the earlier reports at hand. In 1994, the ozone layer was predicted to become thinner until about 1998, and to recover gradually thereafter. Taking into account new information, the Atmospheric Science Panel now expects that the most vulnerable period for ozone depletion will be extended into the coming two decades. Scientific studies are continuing on the most important effects, and on what can be done to prevent or mitigate these. The present assessment deals with the results of such investigations. These repeatedly give reasons for concern for potential effects, but relatively little progress has been made in quantifying these effects. The more the investigators look into the problems, the more the complexity becomes apparent. Nevertheless, the knowledge is accumulating. In comparison with the earlier assessments on effects of ozone depletion, the present report has a new section, Frequently Asked Questions.

The carcinogenic risks of modern tanning equipment: Is UV-A safer than UV-B?

SummaryAn animal experiment is presented in which three groups of albino hairless mice (Skh-hr 1) were exposed to daily doses of either UV-B or UV-A to study carcinogenesis. The UV-A was filtered carefully so as to eliminate contaminating UV-B. The doses required for acute effects (erythema and edema) were also determined for the two radiation modalities. In order to study the relative carcinogenic risks of exposures to UV-A and to UV-B, for both modalities, the doses causing skin tumors were compared to the doses required for eliciting acute effects in the skin.In the experiment on carcinogenesis all animals developed tumors, the ones exposed to UV-A as well as the ones exposed to UV-B. A striking difference, however, was that the induction times of the first tumors showed a larger spread in the mice exposed to UV-A than in the UV-B groups. Also, the development of successive tumors in each individual mouse was more spread in time in the UV-A group. A second difference between the effects on the skin was that in the animals exposed to UV-B no skin reactions were seen until the tumors developed. However, in most UV-A exposed animals, a marked scratching, probably caused by severe itching, and hyperkeratosis preceded the development of the tumors.Histologically at least 60% of the larger tumors induced by UV-A appeared to be squamous cell carcinomas. This finding is very similar for UV-B induced tumors. The elastic fibers in the UV-A exposed animals were also examined and actinic elastosis was observed.Experience has proven that the doses for acute affects in man and mouse are at least proportional to human tanning doses. Comparison of the doses of UV-A and UV-B required for the induction of tumors and for acute reactions of the skin, therefore, leads to the conclusion that the carcinogenic risks of tanning by UV-A and of tanning by UV-B are in the same order of magnitude.

The consequences for human health of stratospheric ozone depletion in association with other environmental factors

Due to the implementation of the Montreal Protocol, which has limited, and is now probably reversing, the depletion of the stratospheric ozone layer, only modest increases in solar UV-B radiation at the surface of the Earth have occurred. For many fair-skinned populations, changing behaviour with regard to exposure to the sun over the past half century - more time in the sun, less clothing cover (more skin exposed), and preference for a tan - has probably contributed more to greater levels of exposure to UV-B radiation than ozone depletion. Exposure to UV-B radiation has both adverse and beneficial effects on human health. This report focuses on an assessment of the evidence regarding these outcomes that has been published since our previous report in 2010. The skin and eyes are the organs exposed to solar UV radiation. Excessive solar irradiation causes skin cancer, including cutaneous malignant melanoma and the non-melanoma skin cancers, basal cell carcinoma and squamous cell carcinoma, and contributes to the development of other rare skin cancers such as Merkel cell carcinoma. Although the incidence of melanoma continues to increase in many countries, in some locations, primarily those with strong sun protection programmes, incidence has stabilised or decreased over the past 5 years, particularly in younger age-groups. However, the incidence of non-melanoma skin cancers is still increasing in most locations. Exposure of the skin to the sun also induces systemic immune suppression that may have adverse effects on health, such as through the reactivation of latent viral infections, but also beneficial effects through suppression of autoimmune reactivity. Solar UV-B radiation damages the eyes, causing cataracts and pterygium. UV-B irradiation of the skin is the main source of vitamin D in many geographic locations. Vitamin D plays a critical role in the maintenance of calcium homeostasis in the body; severe deficiency causes the bone diseases, rickets in children and osteomalacia in adults. Although many studies have implicated vitamin D deficiency in a wide range of diseases, such as cancer and cardiovascular disease, more recent evidence is less compelling, with meta-analyses of supplementation trials failing to show a beneficial effect on the health outcomes that have been tested. It continues to be difficult to provide public health messages to guide safe exposure to the sun that are accurate, simple, and can be used by people with different skin types, in different locations, and for different times of the year or day. There is increasing interest in relating sun protection messages to the UV Index. Current sun protection strategies are outlined and assessed. Climatic factors affect the amount of UV radiation received by the skin and eyes, separately from the effect of ozone depletion. For example, cloud cover can decrease or increase the intensity of UV radiation at Earths surface and warmer temperatures and changes in precipitation patterns may alter the amount of time people spend outdoors and their choice of clothing. The combination of changes in climate and UV radiation may affect the number of pathogenic microorganisms in surface waters, and could have an impact on food security through effects on plant and aquatic systems. It remains difficult to quantify these effects and their possible importance for human health.

UVA-induced tumours in pigmented hairless mice and the carcinogenic risks of tanning with UVA.

SummaryAn animal experiment is presented in which two groups of pigmented hairless mice were exposed daily to suberythemal doses of UVA to study tumourigenesis. The aim of the study was to estimate the carcinogenic risks of tanning by UVA. The pigmented hairless mice, Skh-hr2, were separated by selective breeding into two groups, the “browns” and the “blacks”. Both groups were exposed daily to UVA from fluorescent UVA lamps (Philips TL40W/09) purified by rigorously filtering out the shorter wavelengths. No acute actinic damage was observed after any exposure. However, in most UVA exposed animals, especially in the blacks, a marked scratching preceded the development of tumours. Hyperkeratosis was also observed. All animals developed tumours. Histopathologically at least 60% of the tumours were squamous cell carcinomas. Depositions of melanophages were observed, but no melanomas. It is beyond any doubt that UVA is carcinogenic in laboratory animals. The present state of knowledge justifies no preference for tanning with UVA over tanning with UVB.

A dose-response model for skin cancer induction by chronic u.v. exposure of a human population

A dose-response model, based on the results of animal experiments, is presented for skin cancer induction in a human population by chronic exposure to ultraviolet radiation. The model takes into account a variety of exposure habits and susceptibilities of the individuals in the population. The required input data for the dose-response relationship are the age specific incidences of the population in question. Calculations based on this model can be used as a step in the evaluation of the effect which a reduction of stratospheric ozone would have on the non-melanoma skin cancer incidence. As an example an evaluation for the white population of the U.S.A. is presented. The estimate resulting from this evaluation agrees fairly well with earlier estimates based on combined climatological and epidemiological data.

The dose-response relationship for tumourigenesis by UV radiation in the region 311 – 312 nm

Groups of hairless mice were irradiated daily with Philips TL01 UVB sources. This type of lamp has become available recently and was developed for UVB phototherapy of psoriasis. The TL01 emits radiation in a narrow band around 311-312 nm. Tumours developed on all animals. The dose-response relationship had practically the same shape as that found in a similar experiment with Westinghouse FS40 sunlamps; the tumour induction time appeared to be proportional to the daily dose to a power of -0.58. An additional experiment was performed with a TL01 from which the shorter wavelengths were filtered away. This reduced the carcinogenic effectiveness by a factor of 2.3. The potential of the filtered lamp for phototherapy of psoriasis is discussed.

THEORY OF ULTRAVIOLET ERYTHEMA

Abstract— A quantitative theory of ultraviolet erythema has been developed on the basis of the diffusion equation of Fick. Relationships derived theoretically have been tested against observations. The 300 nm‐erythema shows reasonable agreement with the diffusion theory, the 250 nm‐erythema does not. The hypothesis is advanced that U.V. radiation has two distinct erythemal effects on the skin:one (200 — 400 nm) by action of the radiation on the dermis and one (300 nm) by action of the radiation on the epidermis.