ACUTE N-(3,5-DICHLOROPHENYL) SUCCINIMIDE NEPHROTOXICITY IN FEMALE FISCHER-344 RATS

The agricultural fungicide N-(3,5-dichlorophenyl)succinimide (NDPS) is an established nephrotoxicant in male Fischer 344 rats at i.p. doses of greater than or equal to 0.4 mmol/kg. Since gender differences ofte n exist in the susceptibility to toxicants, the nephrotoxic potential of NDPS was examined in female Fischer 344 rats. Rats (4-5/group) were administered NDPS (0.1, 0.2, 0.4, or 1.0 mmol/kg, i.p.) or vehicle (s esame oil, 2.5 ml/kg) and renal function monitored for 48 h. At a dose of 0.1 mmol/kg, NDPS had no effect on renal function. However, admini stration of NDPS at a dose of 0.2 or 0.4 mmol/kg resulted in marked ne phrotoxicity characterized by diuresis, increased proteinuria, glucosu ria, hematuria, elevated blood urea nitrogen (BUN) concentration and k idney weight, decreased organic ion accumulation and proximal tubular necrosis. NDPS treatment of 1.O mmol/kg resulted in oliguric renal fai lure rather than polyuric renal failure in 3 of 4 rats. Proximal tubul ar damage was observed primarily in the S-3 Segment of the proximal tu bule in NDPS-treated female rats, while in male rats the S, and S-3 se gments are the initial renal targets. These results demonstrate that f emale Fischer 344 rats are more susceptible to NDPS nephrotoxicity tha n male Fischer 344 rats and that the site of the renal lesion is gende r dependent.