Nephrotoxicity screening in rats; general approach and establishment of test criteria.
The concept of a nephrotoxicity screening test that is based on quantitative assessment of urine collected under standardized conditions for 15.5 h is presented. One to eight urine collections were performed in large numbers of untreated female Sprague-Dawley rats. Normal values for water consumption, urine volume, pH, and excretion of protein, gamma-glutamyltranspeptidase, malate dehydrogenase, electrolytes, glucose, amino acids, leukocytes, erythrocytes, epithelia, unspecified cells and cylinders were determined. Test criteria were established based on the statistical distribution of these measurements. In rats repeatedly placed in metabolism cages, a statistically significant decrease in leukocyte excretion and an increase in excretion of epithelia and unspecified cells were observed. All other variables did not change with time.
Zbinden
G
G
Institute of Toxicology, Swiss Federal Institute of Technology, Schwerzenbach.
Fent
K
K
Thouin
M H
MH
D000818:Animals; D004326:Drinking; D004353:Drug Evaluation, Preclinical; D005260:Female; D007674:Kidney Diseases / Q000139:chemically induced* / Q000652:urine; D008297:Male; D011507:Proteinuria / Q000139:chemically induced; D051381:Rats; D013997:Time Factors; D014556:Urine / Q000166:cytology; D014563:Urodynamics / Q000187:drug effects