NEPHROTOXIC POTENTIAL OF N-(3,5-DICHLOROPHENYL)GLUTARIMIDE AND N-(3,5-DICHLOROPHENYL)GLUTARAMIC ACID IN FISCHER-344 RATS

The agricultural fungicide N-(3,5-dichrorophenyl)succinimide (NDPS) pr oduces kidney damage in rats. Although many NDPS analogues have been s creened as possible nephrotoxicants, the one-carbon homologue, N-(3,5- dichlorophenyl)glutarimide (NDPG), has not been evaluated. This study examined the nephrotoxic potential of NDPG and a putative metabolite, N-(3,5-dichlorophenyl)glutaramic acid (NDPGA). Male Fischer 344 rats ( N=3-4 per group) were administered a single i.p. injection in corn oil of NDPG or NDPGA (0.4 or 1.0 mmol/kg), NDPS (0.4 mmol/kg), or corn oi l alone. Renal function was monitored for 48 h. In contrast to NDPS, N DPG and NDPGA did not significantly alter renal function or kidney mor phology when compared to corn oil-treated controls. These experiments show that replacement of the succinimide ring in NDPS with a glutarimi de ring abolishes toxicity.