A 4-WEEK REPEATED PERCUTANEOUS DOSE TOXICITY STUDY OF CALCIPOTRIOL (MC903)FOLLOWED BY A 4-WEEK RECOVERY TEST IN DOGS

• Published in: Journal of toxicological sciences Vol. 21; no. SupplementII; pp. 309 - 323
• Main Authors: IMAIZUMI, Takashi, TSURUTA, Masaaki, KOIKE, Yoshihide, ONO, Masahiro, SHIRAKAWA, Kiyomi, NAGATA, Mitsuhiro, KONISHI, Ryoji
• Format: Journal Article
• Language: English; Japanese
• Published: Tokyo The Japanese Society of Toxicology 01.07.1996; Japanese Society of Toxicology
• Subjects: Administration, Cutaneous; Animals; Beagle dogs; Calcitriol - administration & dosage; Calcitriol - analogs & derivatives; Calcitriol - toxicity; Calcium - urine; Dermatologic Agents - administration & dosage; Dermatologic Agents - toxicity; Dogs; Drug Administration Schedule; Female; gamma-Globulins - metabolism; Hyperplasia; Leukocyte Count - drug effects; Male; Organ Size - drug effects; Skin - drug effects; Skin - pathology; Thymus Gland - drug effects; Thymus Gland - pathology
• ISSN: 0388-1350; 1880-3989
• DOI: 10.2131/jts.21.SupplementII_309

A 4-week repeated percutaneous dose toxicity of calcipotriol (MC903), an anti-psoriasic agent, followed by a 4-week recovery was studied in beagle dogs at doses of 0.04, 0.4 and 4 μg/kg/day. 1. In general conditions, reddening, desquamation, rash, and wet and hot skin were observed at the skin of application site at 4 μg/kg/day. 2. In urinalysis, a tendency to an increase in Ca level, was observed at 4 μg/kg/day. In hematology, an increase in the segmented neutrophils and tendency to a decrease in the lymphocyte counts were observed at 4 μg/kg/day. In biochemistry of serum, an increase in γ-globulin ratio, and decreases in A/G and albumin ratios were observed at 4 μg/kg/day. 3. In organ weights, tendency to decreases of the absolute and relative weights in the thymus was observed at 4 μg/kg/day. 4. Histopathological examination revealed squamous cell hyperplasia and hyperkeratosis at the skin of application site at 4 μg/kg/day. 5. The above changes disappeared after the 4-week recovery period and suggested that they were reversible. 6. On the basis of results obtained in the present study, it is considered that 0.4 μg/kg/day is the no-toxic dose of MC903 applied percutaneously in both sexes of beagle dogs.