[Toxicological examination of pure diflucortolone valerate and its formulations as ointment, fatty ointment and cream in animal experiments (author's transl)]

On the basis of absolute DL50 values 6alpha,9-difluor-11beta-hydroxy-16alpha-methyl-21-valeryloxy-1,4-pregnadiene-3,20-dione (diflucortolone valerate, Nerisona) is virtually non-toxic after single oral administration (mouse greater than 4 g/kg, rat ca. 3.1 g/kg, dog greater than 1 g/kg). Given s.c. (LD50 mouse ca. 180 mg/kg, rat ca. 13 mg/kg) and i.p. (LD50 mouse ca. 450 mg/kg, rat ca. 98 mg/kg) it is highly active and therefore produces also toxic effects. The formulations Nerisona ointment, fatty ointment and cream have proven practically non-toxic in rats after single oral gavage (LD50 greater than 33 g/kg). The daily s.c. administration over 6 weeks revealed systemic glucocorticoid effects in rats at 0.0004 mg/kg and in dogs at 0.04 mg/kg. Similar effects were seen in dogs after daily dermal treatment for 13-14 weeks with Nerisona ointment at 100 mg/kg body weight. On the skin of rabbits and dogs there were no differences in the reaction at the application site between Nerisona ointment, fatty ointment and cream and the corresponding ointment, or cream bases by daily dermal administration for 28 days. However, the 13-14 week dermal study in dogs with Nerisona ointment revealed atrophy of the epidermis at the application site in several cases. The daily dermal application of Nerisona ointment during organogenetic phases of pregnancy caused embryotoxic effects in rats at 500 mg/kg and in rabbits at 50 mg/kg. All of these findings are discusses as well-known glucocorticosteroid effects.