Acute nephrotoxicity of isomeric N-(dichlorophenyl)succinimides in Sprague-Dawley and Fischer 344 rats.
Previous studies have shown that reducing the chlorine content of the experimental agricultural fungicide N-(3,5-dichlorophenyl)succinimide (3,5-NDPS) produces compounds with reduced nephrotoxic potential. The purpose of this study was to determine the importance of the ring position of the two chlorine atoms for the nephrotoxic potential of 3,5-NDPS in rats. Male Sprague-Dawley or Fischer 344 rats were administered a single intraperitoneal injection of a N-(dichlorophenyl)succinimide (0.4 or 1.0 mmol/kg) or vehicle (2.5 ml/kg), and renal function was monitored at 24 and 48 hr. The most nephrotoxic NDPS isomer in both rat strains was 3,5-NDPS. In Sprague-Dawley rats 2,4-, 2,5- and 3,4-NDPS were weakly nephrotoxic. In Fischer 344 rats, 2,4-NDPS (1.0 mmol/kg) and 3,5-NDPS (0.4 mmol/kg) produced similar nephrotoxicity. Weak renal effects were produced by 3,4-NDPS in Fischer 344 rats. The order of increasing nephrotoxicity did not correlate well with the increasing partition coefficients or fungicidal activities of the compounds. These results indicate that 3,5-NDPS is the most nephrotoxic NDPS isomer in rats, and that partition coefficients alone are not good predictors of nephrotoxic potential in this series. In addition, these results do not support a correlation between the fungicidal and nephrotoxic mechanisms of action of these compounds.
D000818:Animals; D001806:Blood Urea Nitrogen; D004305:Dose-Response Relationship, Drug; D007536:Isomerism; D007668:Kidney / Q000187:drug effects* / Q000473:pathology; D007672:Kidney Cortex / Q000378:metabolism; D007684:Kidney Tubules / Q000187:drug effects / Q000473:pathology; D008297:Male; D009929:Organ Size / Q000187:drug effects; D051381:Rats; D011916:Rats, Inbred F344; D011919:Rats, Inbred Strains; D013388:Succinimides / Q000633:toxicity* / Q000652:urine; D014556:Urine; D010130:p-Aminohippuric Acid / Q000378:metabolism
D013388:Succinimides; C007352:N-(3,5-dichlorophenyl)succinimide; D010130:p-Aminohippuric Acid