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.
Forbes
P Donald
PD
Argus Research, Charles River Laboratories, Inc. Horsham, PA 19044, USA. forbes@toxarus.com
Beer
Janusz Z
JZ
Black
Homer S
HS
Cesarini
Jean-Pierre
JP
Cole
Curtis A
CA
Davies
Ronald E
RE
Davitt
John M
JM
deGruijl
Frank
F
Epstein
John
J
Fourtanier
Anny
A
Green
Adèle
A
Koval
Thomas
T
Ley
Ronald D
RD
Mascotto
Romano
R
Morison
Warwick
W
Osterberg
Robert
R
Sliney
David
D
Urbach
Frederick
F
van der Leun
Jan C
JC
Young
Antony R
AR
D000818:Animals; D015197:Carcinogenicity Tests / Q000379:methods* / Q000592:standards*; D004354:Drug Screening Assays, Antitumor / Q000379:methods* / Q000592:standards*; D006801:Humans; D009381:Neoplasms, Radiation-Induced / Q000139:chemically induced*; D014466:Ultraviolet Rays