Standardized protocols for photocarcinogenesis safety testing.

Solar ultraviolet radiation (UVR) is recognized as a major cause of non-melanoma skin cancer in man. Skin cancer occurs most frequently in the most heavily exposed areas and correlates with degree of outdoor exposure. The incidence of skin cancer is also increased by contact with photosensitizing drugs and chemicals such as psoralens, coal tars and petroleum stocks. Other substances which do not act as photosensitizers, such as immunosuppressants taken by organ transplant recipients, also increase the risk of skin cancer. The U.S. Food and Drug Administration requests, on a case-by-case basis, that risk of enhanced photocarcinogenesis is assessed for many classes of drugs. Health Canada's Therapeutic Products Programme has issued a Notice of Intent to regulate pharmaceutical products which may enhance carcinogenicity of the skin induced by ultraviolet radiation. Other national regulatory agencies review such data when they exist, but their own requirements emphasize batteries of short-term in vitro and in vivo tests. While they may support drug development strategies, short-term tests have yet to be validated as predictors of the ability of drugs or chemicals to enhance photocarcinogenesis. Published protocols now describe study designs and procedures capable of determining whether test agents enhance the rate of formation of UVR-induced skin tumors.

Photocarcinogenesis: measuring the reproducibility of a biologic response to ultraviolet radiation exposure in mice.

New drugs undergo safety evaluations of many types. For some drugs, a photocarcinogenesis study forms one of the elements in the overall toxicology package. Photocarcinogenesis studies are designed to evaluate a drug's ability to modify the growth and development of ultraviolet radiation (UVR)-induced skin tumors in albino hairless mice. "Exposure control" groups in such studies receive the UVR, either alone, or in combination with the "vehicle" or carrier associated with each study. This report presents skin tumor data from control groups compiled from nine consecutive studies conducted at this testing facility. The endpoints evaluated included median tumor onset, mortality-free prevalence and tumor yield. "Historical control data" are considered essential for designing, monitoring, interpreting and evaluating studies of a given type. In addition, a compilation of such control data can illustrate trends or provide measures of reproducibility more reliably than can individual studies. This data set shows how clearly the UVR-induced skin tumor onset time is dependent on UVR dose, how skin tumors develop sooner in female mice than in male mice at a low UVR exposure dose, and that topical administration of certain vehicle formulations can enhance photocarcinogenesis.