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FUNCTIONAL TERATOGENS OF THE RAT KIDNEY I. COCHICINE, DINOSEB, AND METHYL SALICYLATE
Citation:
Daston, G. AND e. al. FUNCTIONAL TERATOGENS OF THE RAT KIDNEY I. COCHICINE, DINOSEB, AND METHYL SALICYLATE. U.S. Environmental Protection Agency, Washington, D.C., EPA/600/J-88/541 (NTIS PB91109223), 1988.
Description:
Substances known or suspected to cause subtle or transient anatomical alterations in renal development were administered prenatally or neonatally to rats in order to determine whether they are capable of altering renal functional development. olchicine alters mitotic activity and cytoskeletal structure and is teratogenic in many species. ince the kidney of the newborn rat undergoes extensive cellular proliferation and nephron differentiation, it is possible that neonatal administration of colchicine may affect nephron development. inoseb and methyl salicylate have previously been reported to produce a high incidence of dilated renal pelvis in the term rat fetus. olchicine was injected sc at 75 ug/kg, to Postnatal Day (PD) 1 Sprague-Dawley rats. inoseb was administered ip to pregnant Sprague-Dawley rats on Gestation Days 10-12 at doses of 8 or 10.5 mg/kg/day, and methyl salicylate was administered ip at doses of 200, 250, or 300 mg/kg/day on Gestation Days 11-12. enal function was examined in pups from immediately after birth through weaning. aximal urine concentrating ability was measured after DDAVP (desmopressin acetate, a vasopressin analog) injection in suckling rats, and after 24 hr of water deprivation in weanlings. roximal tubule transport was measured in renal cortical slices. asal urinary parameters, including urine flow, osmolality, pH, and chloride content, were measured. olchicine treatment had no effect on body weight or kidney weight. here was a significant decrease in maximal urine osmolality in PD 30 rats measured after 24 hr of water deprivation. he urine concentrating deficit detected in functionally mature PD 30 rats suggests that colchicine treatment during renal histogenesis causes a latent deficit in medullary function in the absence of any gross morphological effects. he 10.5 mg/kg/day/dose of dinoseb caused a weight reduction in neonates which persisted after weaning. he results indicate that there is a temporary delay in the maturation of urine concentrating ability in rats transplacentally exposed to methyl salicylate or dinoseb.