In vivo and in vitro effects of azaconazole on renal function in the Fischer 344 rat

Azaconazole is an experimental agricultural fungicide which has shown promise for use in controlling powdery mildew on crops and bean rust. This study examined the nephrotoxic potential of a single intraperitoneal azaconazole injection (0.4 or 0.6 mmol/kg) or daily azaconazole administration (0.1 or 0.3 mmol/kg/day) for 7 days in male Fischer 344 rats. The in vitro effects of azaconazole on the accumulation of organic ions by renal cortical slices also were examined. Acute azaconazole administration (0.4 or 0.6 mmol/kg, i.p.) produced a marked decrease in urine volume at 6 h. By 48 h urine volume was still decreased in the 0.6-mmol/kg group but not the 0.4-mmol/kg group. Proteinuria (++) and slight hematuria were seen in the 0.6-mmol/kg group on both treatment days. Accumulation of p-aminohippurate (PAH) by renal cortical slices was stimulated in both azaconazole-treated groups while tetraethylammonium (TEA) accumulation was not altered. No changes in blood urea nitrogen concentration, kidney weight or renal morphology were produced at 48 h postinjection by either azaconazole dose. Daily administration of azaconazole (0.1 or 0.3 mmol/kg/day) did not significantly alter any of the renal parameters studied. Incubation of renal cortical slices with increasing concentrations of azaconazole from 10(-5) M to 10(-3) M caused a continued reduction in TEA accumulation. PAH accumulation was decreased significantly following incubation with azaconazole 10(-5) or 10(-3) M. These results indicate that azaconazole is capable of producing acute, reversible renal effects at doses equal to or less than 0.6 mmol/kg and altering organic ion transport both in vivo and in vitro. The lack of marked renal effects following exposure to azaconazole is favorable for the development of this compound as an agricultural fungicide.