[A 52-week percutaneous toxicity study of prednisolone farnesylate (PNF) gel in beagle dogs with a recovery period of 8 weeks].
The toxicity of Prednisolone farnesylate (PNF) gel, a synthetic glucocorticoid, was investigated in the Beagle dog. PNF gel was administered percutaneously at doses of 0.05, 0.2 and 0.8 mg/kg/day for 52 weeks, then the drug was with held for 8 weeks to evaluate reversibility. The results are summarized in the following. 1. In the 0.05 mg/kg/day and above groups, hypotrichosis in the application site of the skin, thinning of the skin and atrophy of the appendages, and in the 0.2 mg/kg/day and above groups a tendency toward retarded body weight gain, were observed. 2. In the 0.2 mg/kg/day and above groups, a drop in the lymphocyte ratio, a rise in GOT activity and A1P level, and in the 0.8 mg/kg/day group a rise in free fatty acid were observed. 3. In the 0.2 mg/kg/day group and above groups, atrophy of the zona fasciculata and zona reticularis were observed. In the 0.8 mg/kg/day group, a decrease in the weight of the thymus and adrenal glands, and a increase in the weight of the liver, were observed. 4. At the end of the recovery period, most of the changes disappeared, except for those in the adrenals and treated area. From the above results, under the conditions of this study, it was concluded that when the changes observed in the application site of the skin in each group were not taken into consideration, the toxicological no effect level was 0.05 mg/kg/day for both males and females and the overt toxic dose level was 0.8 mg/kg/day.
Nagashima
Y
Y
Bozo Research Center Inc., Tokyo, Japan.
Ide
M
M
Akai
H
H
Tamura
K
K
Shimura
K
K
Tanaka
H
H
Tanaka
G
G
D000279:Administration, Cutaneous; D000311:Adrenal Glands / Q000473:pathology; D000818:Animals; D001774:Blood Chemical Analysis; D001835:Body Weight / Q000187:drug effects; D004285:Dogs; D005204:Farnesol / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000633:toxicity; D005243:Feces / Q000737:chemistry; D005260:Female; D005782:Gels; D006403:Hematologic Tests; D008297:Male; D009929:Organ Size / Q000187:drug effects; D011239:Prednisolone / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000633:toxicity; D012867:Skin / Q000473:pathology; D013997:Time Factors
D005782:Gels; C080069:prednisolone farnesylate; D005204:Farnesol; D011239:Prednisolone