A 4-week repeated percutaneous dose toxicity study of calcipotriol (MC903) followed by a 4-week recovery test in dogs.
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 micrograms/kg/day. 1. In general conditions, reddening, desquamation, rash, and wet and hot skin were observed at the skin of application site at 4 micrograms/kg/day. 2. In urinalysis, a tendency to an increase in Ca level, was observed at 4 micrograms/kg/ day. In hematology, an increase in the segmented neutrophils and tendency to a decrease in the lymphocyte counts were observed at 4 micrograms/kg/day. In biochemistry of serum, an increase in gamma-globulin ratio, and decreases in A/G and albumin ratios were observed at 4 micrograms/kg/day. 3. In organ weights, tendency to decreases of the absolute and relative weights in the thymus was observed at 4 micrograms/kg/day. 4. Histopathological examination revealed squamous cell hyperplasia and hyperkeratosis at the skin of application site at 4 micrograms/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 microgram/kg/day is the no-toxic dose of MC903 applied percutaneously in both sexes of beagle dogs.
Imaizumi
T
T
Japan Seigiken Research Center Co., Ltd., Shizuoka, Japan.
Tsuruta
M
M
Koike
Y
Y
Ono
M
M
Shirakawa
K
K
Nagata
M
M
Konishi
R
R
D000279:Administration, Cutaneous; D000818:Animals; D002117:Calcitriol / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000633:toxicity; D002118:Calcium / Q000652:urine; D003879:Dermatologic Agents / Q000008:administration & dosage / Q000633:toxicity*; D004285:Dogs; D004334:Drug Administration Schedule; D005260:Female; D006965:Hyperplasia; D007958:Leukocyte Count / Q000187:drug effects; D008297:Male; D009929:Organ Size / Q000187:drug effects; D012867:Skin / Q000187:drug effects / Q000473:pathology; D013950:Thymus Gland / Q000187:drug effects / Q000473:pathology; D005719:gamma-Globulins / Q000378:metabolism
D003879:Dermatologic Agents; D005719:gamma-Globulins; C055085:calcipotriene; D002117:Calcitriol; D002118:Calcium