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The effect of ortho toluenesulfonamide and sodium saccharin on the urinary tract of neonatal rats.
Authors:D L Arnold  C A Moodie  P F McGuire  B T Collins  S M Charbonneau  I C Munro
Affiliation:Toxicology Research Division, Bureau of Chemical Safety, Food Directorate, Health Protection Branch, Ottawa K1A 0L2, Canada
Abstract:The transplacental and postnatal effects of ortho-toluenesulfonamide (o-TS, 99.9% pure) and o-TS-free sodium saccharin on the urinary tract of neonatal rats, were examined in two experiments. In the first, o-TS in corn oil was administered by gavage throughout gestation and lactation at dosages of 0, 40, 100, or 250 mg o-TS/kg. After weaning, the pups were fed diets containing sufficient o-TS to provide the same dosages their respective dams received. Pups were killed at 8, 15, 21, and 105 days postpartum. The kidneys, urinary bladders, and urine filtrates were examined by light microscopy for calculi and the two organs were also examined histologically. A significant dose-response (p < 0.05) was found for the incidence of bladder calculi in 21-day-old pups and in 105-day old male and female rats. In a second experiment, male and female rats received one of the following dietary treatments for 100 days prior to mating: 0 (control), 2.5, 25, or 250 mg o-TS/kg, 250 mg o-TS/kg with 1% NH4Cl in the drinking water, or 5% sodium saccharin. The dams were fed their respective diets during mating, gestation, and lactation. After weaning, the pups received their respective parents' diet. Pups were killed at 8, 21, and 105 days postpartum; kidneys, urinary bladders, and urine filtrates were examined as above. A significant dose-response (p < 0.05) was only found for the incidence of renal calculi and bladder lesions in 8-day-old pups from dams given diets that contained o-TS. However, there was no increased incidences of any urinary tract lesion in rats fed diets containing 250 mg o-TS and given 1% NH4Cl in the drinking water, or in those fed a diet containing 5% sodium saccharin, or in older animals exposed only to o-TS. The administration of o-TS during gestation, lactation, and in the diet after weaning predisposes neonatal animals to urolithiasis and/or bladder lesions. These effects were not observed when a 1% solution of NH4Cl was provided. Sodium saccharin, free of o-TS, did not have a similar effect.
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