[Frontiers in Bioscience 8, d848-854, May 1, 2003]

STANDARDIZED PROTOCOLS FOR PHOTOCARCINOGENESIS SAFETY TESTING

P. Donald Forbes 1, Janusz Z. Beer 2, Homer S. Black 3, Jean-Pierre Cesarini 4, Curtis A. Cole 5, Ronald E. Davies 6, John M. Davitt 7, Frank deGruijl 8, John Epstein 9, Anny Fourtanier 10, Adèle Green 11, Thomas Koval 12, Ronald D. Ley 13, Romano Mascotto 14, Warwick Morison 15, Robert Osterberg 16, David Sliney 17, Frederick Urbach 18, Jan C. van der Leun 19, and Antony R. Young 20

1Argus Research, Charles River Laboratories, Inc. Horsham, PA 19044, USA; 2US Food and Drug Administration, Center for Devices and Radiologic Health, Rockville, MD, 20852, USA; 3 Veterans Affairs Medical Center and Baylor College of Medicine, Houston, Texas 77030, USA; 4 Foundation Rothchild, 75019 Paris, France; 5 Johnson & Johnson Consumer Products Co., Skillman, NJ 08558, USA; 6 Chisholm Township, Ontario POH 1ZO, Canada; 7 Regulatory Affairs Services, Silver Spring, MD 20904, USA; 8 Dermatology, Leiden University Medical Center, Leiden, Netherlands; 9 450 Sutter St., Suite 1306, San Francisco, CA 94108, USA; 10 Groupe Dermato-Biologie, L'Oreal, 92583 Clichy Cedex, Paris, France; 11 Queensland Institute Medical Centre, Brisbane, Queensland 4029, Australia; 12 NCRP, Suite 800, Bethesda, MD 20814 USA; 13 University of New Mexico, Albequerque, NM 87131-5218, USA; 14 Corporate Research and Development, L'Oreal, 92583 Clichy Cedex, Paris, France; 15 10753 Falls Rd., Suite 205, Lutherville, MD 21093, USA; 16 U.S. Food and Drug Administration, Rockville, MD 20857, USA; 17 U.S. Army Environmental Hygiene Agency, Aberdeen Proving Grounds, MD 21010-5422, USA; 18 438 Clairemont Road, Villanova, PA 19085-1706 USA; 19 EcoSys, Utrecht, Netherlands; 20 St. John's Institute of Dermatology, King's College, London, SE1 7EH, United Kingdom

TABLE OF CONTENTS

1. Abstract
2. Introduction
3. A Laboratory Protocol Based on Simulated Solar UVR
4. Recommended Study Design
5. Acknowledgement
6. References

1. ABSTRACT

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.