The fate of 2,4,5-trichlorophenoxyacetic acid (2,4,5-T) following oral administration to rats and dogs
Piper, W.N.; Rose, J.Q.; Leng, M.L.; Gehring, P.J.
Toxicology and Applied Pharmacology 26(3): 339-351
1973
ISSN/ISBN: 0041-008X PMID: 4767573 DOI: 10.1016/0041-008x(73)90270-6
Accession: 044639491
Clearance of 14C activity from the plasma and its elimination from the body of rats and dogs were determined after single oral doses of [carboxy-14C]2,4,5-T. The half-life values for the clearance of 14C activity from the plasma of rats given doses of 5, 50, 100 or 200 mg/kg were 4.7, 4.2, 19.4 and 25.2 hr, respectively; half-lives for elimination from the body were 13.6, 13.1, 19.3 and 28.9 hr, respectively. The apparent volume of distribution also increased with dose. Urinary excretion of unchanged 2,4,5-T accounted for most of the 14C activity eliminated from the body of rats. A small amount of unidentified metabolite was detected in the urine when rats were given 100 or 200 mg/kg but not 5 or 50 mg/kg. These results show that the distribution, metabolism and excretion of 2,4,5-T are markedly altered when large doses are administered. In dogs given 5 mg/kg, the half-life values for clearance from plasma and elimination from the body were 77.0 and 86.6 hr, respectively, offering a plausible explanation of why 2,4,5-T is more toxic in dogs than in rats. Appreciable excretion in the feces was noted and three unidentified metabolites were detected in urine of dogs, indicating a considerable difference in metabolism of 2,4,5-T by dogs and rats given the same dose.