TRANSPORT OF 2,4,5-TRICHLOROPHENOXYACETATE IN THE ISOLATED, PERFUSED RAT-KIDNEY
The minimal mammalian toxicity of 2,4,5-trichlorophenoxyacetate (2,4,5-T) has been correlated to the rapid urinary elimination of this herbicide. In the present study, the renal transport of 2,4,5-T was studied in the isolated, perfused rat kidney. When 2,4,5-T (1.86 μM) was present in an albumin perfusate, the 2,4,5-T/inulin clearance ratio was â0.019. For these clearance studies, the glomerular filtration rate (638 μl/min), fractional reabsorption of Na+ (96%) and urine flow 39 μl/min) were within normal limits for this preparation. When the unbound 2,4,5-T (0.46%) in the perfusate was used in clearance calculations, the corrected 2,4,5-T/inulin clearance ratio was greater than 4, indicating net secretion. When a dextran perfusate was used to limit 2,4,5-T binding in the perfusate, the 2,4,5-T/inulin clearance ratio was increased to â6 without any effects on renal function. The secretion of 2,4,5-T was inhibited by probenecid or p-aminohippurate. When a high concentration of 2,4,5-T (1 mM) was present in the perfusate, the clearances of p-aminohippurate and tetraethylammonium were decreased significantly; however, there were concurrent alterations in the glomerular filtration rate, fractional reabsorption of Na+ and urine flow. In conclusion, 2,4,5-T is secreted by the proximal tubule by a p-aminohippurate- and probenecid-sensitive mechanism. However, a high concentration of this herbicide is nephrotoxic. Since this compound is removed primarily by the kidney, such nephrotoxicity could explain the dramatic increase in the systemic toxicity of 2,4,5-T at high doses.