Evaluation of a general toxicity study incorporating phototoxicity assessments in Sprague-Dawley rats

Abstract

-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 singledose group was irradiated with UV-A and UV-B after a single administration of the drug. The repeateddose 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 T max . 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.

Multi-site study of an <i>in vivo</i> phototoxicity evaluation in Sprague-Dawley (SD) rats aimed at incorporating the phototoxicity assessments: effects of repeated administration and toxicokinetic blood collection on drug-induced phototoxicity

“…However, the skin scores of the repeated-dose group were lower than those of the single-dose groups at Kaken and Takeda. This attenuation of skin reaction was also previously reported (Yonezawa et al, 2017). No major differences in the T max , C max , or AUC 0-24 values of LMFX were observed throughout the dosing period.…”

“…Regarding the effects of blood sampling, we considered that blood sampling had a very small influence on the phototoxicity assessment as we demonstrated in the previous study (Yonezawa et al, 2017). Additionally, sampling of less than 0.9 mL of blood per day is known as the maximum volume that can be drawn from rats without causing changes in hematological parameters (Kurata et al, 1997).…”

“…We previously demonstrated that phototoxicity assessments could be incorporated into general toxicity studies (Yonezawa et al, 2017). However, this research was performed in only one facility.…”