[A 26-week repeated percutaneous dose toxicity study of calcipotriol (MC903) in rats].
A 26-week repeated percutaneous dose toxicity of calcipotriol (MC903), an anti-psoriasic agent, was studied in Slc:SD rats at doses of 0.8, 4 and 20 micrograms/kg/day as low, mid and high dose levels. 1. No mortality were observed in both sexes of all groups including control. An increased water consumption was observed in females at mid dose and in both sexes at high dose. 2. An increased incidence of the corneal opacity in males at mid dose and in both sexes at high dose was noted significantly as compared with that observed in control. Urinalysis revealed a slight increased urinary volume, increased excretions of Ca and IP, and lower pH in both sexes at more than mid dose. Levels of the serum IP in females and Ca in both sexes were elevated at high dose. 3. The increased weights of the kidney in males and adrenal gland in females were observed at high dose. The kidney in females at mid dose and in both sexes at high dose showed a higher incidence of mineralization than in control. Furthermore, osteosclerosis of the sternum and femur in both sexes, and hyperkeratosis of the skin at application site in females at high dose were observed. Electron microscopic examination revealed no abnormality in the liver and kidney. 4. On the basis of results obtained in the present study, it is considered that 0.8 microgram/kg/day is the no-toxic dose of MC903 applied percutaneously in both sexes of rats.
Kitagaki
T
T
Japan Seigiken Research Center Co., Ltd., Shizuoka, Japan.
Suzuki
T
T
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 / Q000097:blood / Q000652:urine; D003318:Corneal Opacity / Q000139:chemically induced; D003879:Dermatologic Agents / Q000008:administration & dosage / Q000633:toxicity*; D004334:Drug Administration Schedule; D005260:Female; D007642:Keratosis / Q000139:chemically induced; D007668:Kidney / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008297:Male; D008903:Minerals / Q000378:metabolism; D009929:Organ Size / Q000187:drug effects; D010710:Phosphates / Q000097:blood / Q000652:urine; D051381:Rats; D017207:Rats, Sprague-Dawley
D003879:Dermatologic Agents; D008903:Minerals; D010710:Phosphates; C055085:calcipotriene; D002117:Calcitriol; D002118:Calcium