title: Evaluation of skin phototoxicity study using SD rats by transdermal and oral administration.
abstract: Guinea pigs are the most frequently used animals in phototoxicity studies. However, general toxicity studies most often use Sprague-Dawley (SD) rats. To reduce the number of animals needed for drug development, we examined whether skin phototoxicity studies could be performed using SD rats. A total of 19 drugs that had previously been shown to have phototoxic potential and 3 known phototoxic compounds were administered transdermally to guinea pigs and SD rats. Eleven of the potentially phototoxic drugs and 2 of the known phototoxic compounds were also administered orally to guinea pigs and SD rats. After administration, the animals were irradiated with UV-A (10 J/cm(2)) and UV-B (0.25 J/cm(2) in guinea pigs and 0.031 J/cm(2) in SD rats) with doses based on standard phototoxicity study guidelines and the results of a minimum erythema dose test, respectively. In the transdermal administration study, all of the known phototoxic compounds and 7 of the drugs induced phototoxic reactions. In the oral administration study, both known phototoxic compounds and 5 drugs induced phototoxic reactions in both species; one compound each was found to be toxic only in SD rats or guinea pigs. The concordance rate of guinea pigs and SD rats was 100% in the transdermal administration study and 85% in the oral administration study. This study demonstrated that phototoxicity studies using SD rats have the same potential to detect phototoxic compounds as studies using guinea pigs.
authors.affiliation: Pharmacokinetics and Safety Department Drug Research Center Kaken Pharmaceutical Co., Ltd.
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Yonezawa
authors.forename: Tomoka
authors.initials: T
authors.lastname: Ohsumi
authors.forename: Taishi
authors.initials: T
authors.lastname: Miyashita
authors.forename: Akira
authors.initials: A
authors.lastname: Kataoka
authors.forename: Kazuto
authors.initials: K
authors.lastname: Hashimoto
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Nejishima
authors.forename: Haruko
authors.initials: H
authors.lastname: Ogawa
mesh_terms: D000279:Administration, Cutaneous; D000284:Administration, Oral; D000818:Animals; D000873:Anthracenes / Q000008:administration & dosage* / Q000633:toxicity*; D017484:Dermatitis, Phototoxic / Q000209:etiology*; D005260:Female; D006168:Guinea Pigs; D008297:Male; D008730:Methoxsalen / Q000008:administration & dosage* / Q000633:toxicity*; D011829:Radiation Dosage; D017207:Rats, Sprague-Dawley; D012867:Skin / Q000187:drug effects* / Q000528:radiation effects*; D014466:Ultraviolet Rays / Q000009:adverse effects*
chemical_list: D000873:Anthracenes; C034020:anthracene; D008730:Methoxsalen