A 4-week repeated percutaneous dose toxicity study of calcipotriol (MC903) followed by a 4-week recovery test in dogs

Abstract

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 μ/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 μ/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.