Evaluation of phototoxic and photoallergic potentials of 13 compounds by different in vitro and in vivo methods.
Phototoxic side effects of pharmaceutical and cosmetic products are of increasing concern for patients, dermatologists and the chemical industry. Moreover, the need of new chemicals and drugs puts pressure on pre-clinical test methods for side effects, especially interactive adverse-effects with UV-light. So, the predictive potential of different established test methods, which are used regularly in our departments in order to detect the phototoxic potential of chemicals, were analyzed. Namely the fibroblast 3T3 test, the photo hen's egg test, a guinea pig test for measuring acute photoreactions, and a modified Local Lymph Node Assay, the Integrated Model for the Differentiation of Skin Reactions. Various agents with different photoreactive potential were tested: quinolones like Bay y 3118, ciprofloxacin, enoxacin, lomefloxacin, moxifloxacin, ofloxacin, sparfloxacin, as well as promethazine, chlorpromazine, 8-methoxypsoralen and olaquindox serving as control. Special emphasis was taken to evaluate the capability of the employed test procedures to predict phototoxic side effects in patients. Following our results, both in vitro assays were useful tools to detect photoirritancy while the photoallergic potentials of tested compounds were exclusively detected by an in vivo assay. As long as no in vitro model for photoallergy is available, the UV-IMDS should be considered to evaluate photoallergic properties of a supposed photoreactive agent.
Neumann
Norbert J
NJ
Hautklinik, Heinrich-Heine-Universität, Moorenstrasse 5, 40225 Düsseldorf, Germany. neumannt@uni-duesseldorf.de
Blotz
Andrea
A
Wasinska-Kempka
Grazyna
G
Rosenbruch
Martin
M
Lehmann
Percy
P
Ahr
Hans Jürgen
HJ
Vohr
Hans-Werner
HW
D000818:Animals; D002460:Cell Line; D002642:Chick Embryo; D017454:Dermatitis, Photoallergic / Q000473:pathology*; D017484:Dermatitis, Phototoxic / Q000473:pathology*; D004305:Dose-Response Relationship, Drug; D004353:Drug Evaluation, Preclinical / Q000379:methods; D064420:Drug-Related Side Effects and Adverse Reactions; D005260:Female; D006168:Guinea Pigs; D051379:Mice; D008807:Mice, Inbred BALB C; D004364:Pharmaceutical Preparations / Q000008:administration & dosage; D014466:Ultraviolet Rays / Q000009:adverse effects
D004364:Pharmaceutical Preparations