Juvenile toxicity of cyclosporin in the rat

The pups from 32 litters of SD rats were given 0, 1, 3 or 10 mg/kg-d of cyclosporin by oral gavage from 4 to 28 days of age. 10 mg/kg-d resulted in a persistent impairment of the primary antibody response at 10 weeks of age. Indications of systemic toxicity, including the death of 10/64 pups and severely depressed weight gain, were also observed at this dose level. Arteriopathy of the heart and tubular basophilia and edema in the cortico-medullary region of the kidney were observed at 3 and 10 mg/kg-d. In conclusion, while pharmacological effects were seen at all dose levels, the adverse effects of cyclosporin on the development of the immune system in the rat only occurred at a dose level that also induced systemic toxicity.