Pharmacokinetics of 2,4,5-T PGBE ester applied dermally to rats

The pharmacokinetic profile of the herbicide 2,4,5-T PGBE ester (propylene glycol butyl ether esters of 2,4,5-trichlorophenoxyacetic acid) 14C-labeled in the ring was examined in rats given a single dermal application of 5 mg/kg. The rate of absorption of the ester through the skin was lower than the rate of hydrolysis to 2,4,5-T acid and the rate of excretion of 2,4,5-T in the urine. Urinary excretion of radioactivity was apparently first order with a half-life of approximately 24 h. Clearance of radioactivity from blood plasma, liver kidneys, and the remaining carcass was also apparently first order with half-life values ranging from 25 to 37 h. Six days (144 h) after application of the dose, an average of 98.7 +/- 5.1% of the applied radioactivity was recovered in he urine, and approximately 97% of the urinary radioactivity was identified as 2,4,5-T acid. The tissue-to-plasma ratios of 14C activity in liver and kidney were similar to those observed previously in rats given a single iv dose of 5 mg/kg 2,4,5-T acid. The results of this study indicate that the pharmacokinetic model for 2,4,5-T PGBE ester in rats is similar to that for 2,4,5-T acid. This similarity suggests the chronic exposures to 2,4,5-T acid and its PGBE ester would be toxicologically comparable. The low rate of absorption of the ester through the skin suggests that removal of the ester from the skin by washing after exposure might substantially reduce the dose of 2,4,5-T received by this route. Since the urinary excretion rate of 2,4,5-T in humans is known, a similar pharmacokinetic model for humans may be developed to calculate the absorbed dose of 2,4,5-T based on urinary excretion data.