The renal handling of 2,4,5-trichlorophenoxy-acetic acid (2,4,5-T) in the dog

The herbicide 2,4,5-T is actively transported by renal cortical slices of dogs and rats, suggesting that the compound should be rapidly eliminated from the body via the kidneys. The prolonged plasma half-life of 2,4,5-T in the dog (77 hr) indicates that factors other than secretion into the urine are important determinants of elimination in the dog. This study was designed to determine the renal handling of 2,4,5-T in anaesthetized dogs, and an attempt was made to increase excretion of the herbicide with sodium acetate. Injection of 2,4,5-T decreased clearance of p-aminohippurate in a dose-dependent manner, suggesting that the compound was actively secreted. The clearance of the herbicide, however, was exceedingly low, being less than 1% of inulin clearance. The clearance of 2,4,5-T was increased by sodium acetate and by acetazolamide. Additional studies with mannitol, sodium bicarbonate and ammonium chloride demonstrated that clearance of 2,4,5-T was related to urinary pH, but only when the pH exceeded 6, and was not affected by changes in urine volume. Addition of plasma inhibited the transport of 2,4,5-T by renal cortex slices in vitro, suggesting that the low clearance in vivo was due to very tight binding of the herbicide to plasma protein.