Juvenile toxicity of cyclosporin in the rat.
The pups from 32 litters of SD rats were given 0, 1, 3 or 10mg/kg-d of cyclosporin by oral gavage from 4 to 28 days of age. 10mg/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 10mg/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.
Allais
Linda
L
MDS Pharma Services, 329 Impasse du Domaine Rozier, Les Oncins, 69210 Saint-Germain sur l'Arbresle, France. linda.allais@mdsinc.com
Condevaux
Fabienne
F
Fant
Pierluigi
P
Barrow
Paul C
PC
D000284:Administration, Oral; D000818:Animals; D000831:Animals, Newborn; D000833:Animals, Suckling; D000900:Anti-Bacterial Agents / Q000633:toxicity*; D000917:Antibody Formation / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D016572:Cyclosporine / Q000633:toxicity*; D005260:Female; D006321:Heart / Q000187:drug effects; D007107:Immune System / Q000187:drug effects* / Q000254:growth & development; D007668:Kidney / Q000187:drug effects / Q000473:pathology; D008136:Longevity / Q000187:drug effects; D008198:Lymph Nodes / Q000187:drug effects / Q000473:pathology; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D020127:Recovery of Function; D012741:Sexual Maturation / Q000187:drug effects; D013154:Spleen / Q000187:drug effects / Q000473:pathology; D016176:T-Lymphocyte Subsets / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D013950:Thymus Gland / Q000187:drug effects / Q000473:pathology; D013977:Tibia / Q000187:drug effects / Q000254:growth & development; D018675:Toxicity Tests / Q000379:methods*; D028761:Withholding Treatment
D000900:Anti-Bacterial Agents; D016572:Cyclosporine