Examination of the usefulness of 8-MOP in rat retinal phototoxicity assessment

Abstract

According to the guideline for photosafety evaluation of pharmaceuticals (ICH-S10), phototoxicity of the retina should be assessed in animals for systemic drugs that absorb light above 400 nm and it should be considered that the lens in children of less than approximately 10 years of age is not completely protective against wavelengths below 400 nm. For retinal phototoxicity, the ICH-S10 guideline recommends that a reference compound with a light absorption profile within the visible light range (above 400 nm) as a positive control compound, however, there is currently no positive control compound which widely used as a standard. Therefore, we investigated whether 8-MOP (8-Methoxypsoralen), a positive control compound for skin phototoxicity, could be used as a positive control compound for retinal phototoxicity in rats. In this study, 6-week old female SD rats were orally administered once with 8-MOP at 10 and 50 mg/kg and irradiated with UV light for 45 minutes from 1 hour after administration. The rats were euthanized on 3, 7 or 10 day after UV irradiation and histopathological examination of the retina was performed. At 10 and 50 mg/kg, thickening of the retina, and spaces and degeneration/atrophy in the inner nuclear layer, etc. were observed on 3 day after UV irradiation, and atrophy in the outer nuclear layer in the central retina, rod cells and cone cells, etc. were observed on 7 and 10 days after UV irradiation. From the results of this study, 8-MOP was considered to be usable as a positive control compound for phototoxicity evaluation in rats.