Evaluation of a general toxicity study incorporating phototoxicity assessments in Sprague-Dawley rats.
Previously, we showed that phototoxicity assessments in Sprague-Dawley (SD) rats can detect phototoxic potential to the same degree as those in guinea pigs. In this study, we examined whether phototoxicity assessments can be incorporated into general toxicology studies, using SD rats. Three phototoxic compounds were tested. Acridine and 8-methoxypsoralen (8-MOP) were transdermally administered, and 8-MOP and lomefloxacin were orally administered. The animals were allocated to three groups for each compound: single-dose, repeated-dose, and repeated-dose plus toxicokinetics (TK). The single-dose group was irradiated with UV-A and UV-B after a single administration of the drug. The repeated-dose and TK groups were irradiated after 8 days of repeated administration of the drug. Blood samples were also collected from the TK group on days 1 and 7 after administration. The phototoxic compounds resulted in skin reactions in all the groups, with no difference in the degree of skin reaction among the three groups. In the TK measurements, all of the phototoxic compounds were detected in the plasma samples, and the irradiation timing was close to the Tmax. These results indicate that phototoxic potential could be evaluated in the TK group, and phototoxicity assessments could be incorporated into general toxicology studies. This reduces the number of studies and animals required, thus shortening the research and development period, and supporting the 3Rs principle of animal experiments. The study also provides information regarding appropriate irradiation timings, differences between the sexes, and dose-response, in turn enabling the phototoxic risk of the compounds to be clearly evaluated.
Pharmacokinetics and Safety Department Drug Research Center Kaken Pharmaceutical Co., Ltd.
Yutaka
Y
Yonezawa
Taishi
T
Miyashita
Hiroko
H
Ashizawa
Kazuto
K
Hashimoto
Hiroaki
H
Nejishima
Haruko
H
Ogawa
D000166:Acridines / Q000032:analysis / Q000493:pharmacokinetics / Q000633:toxicity*; D000279:Administration, Cutaneous; D000284:Administration, Oral; D000818:Animals; D017484:Dermatitis, Phototoxic; D024841:Fluoroquinolones / Q000097:blood / Q000493:pharmacokinetics / Q000633:toxicity*; D008297:Male; D008730:Methoxsalen / Q000097:blood / Q000493:pharmacokinetics / Q000633:toxicity*; D017319:Photosensitizing Agents / Q000097:blood / Q000493:pharmacokinetics / Q000633:toxicity*; D017207:Rats, Sprague-Dawley; D012867:Skin / Q000187:drug effects; D018675:Toxicity Tests / Q000379:methods*
D000166:Acridines; D024841:Fluoroquinolones; D017319:Photosensitizing Agents; C053091:lomefloxacin; D008730:Methoxsalen