Comparative acute renal effects of three N-(3,5-dichlorophenyl)carboximide fungicides: N-(3,5-dichlorophenyl)succinimide, vinclozolin and iprodione

A large number of carboximides have been synthesized, tested and, in some cases, marketed as agricultural fungicidal agents. One carboximide fungicide N-(3,5-dichlorophenyl)succinimide (NDPS) proved to be both highly efficacious as a fungicide and a nephrotoxin. The purpose of this study was to compare the acute nephrotoxic potential of three N-(3,5-dichlorophenyl)carboximide fungicides [NDPS, vinclozolin (VCLZ) and iprodione (IPDO)] to determine if nephrotoxic potential correlated with fungicidal efficacy among this class of structurally-related agricultural agents. Male Fischer 344 rats (4 rats/group) received a single intraperitoneal injection of a fungicide (0.4 or 1.0 mmol/kg) or vehicle (sesame oil, 2.5 ml/kg), and renal function was monitored at 24 and 48 h. NDPS (0.4 or 1.0 mmol/kg)-induced renal effects were characterized by marked diuresis, increased proteinuria, elevated blood urea nitrogen (BUN) concentration and kidney weights, decreased organic ion accumulation by renal cortical slices and proximal tubular necrosis. In contrast, IPDO and VCLZ (0.4 or 1.0 mmol/kg) administration resulted in only minor or no alterations in the renal function parameters studied and renal morphology. These results suggest that fungicidal efficacy does not correlate with acute nephrotoxic potential among the N-(3,5-dichlorophenyl)carboximide fungicides.