Oral and dermal application of 2,4-dichlorophenoxyacetic acid sodium and dimethylamine salts to male rats: investigations on absorption and excretion as well as induction of hepatic mixed-function oxidase activities.
Absorption and urinary excretion of 2,4-dichlorophenoxyacetic acid sodium (sodium 2,4-D) and 2,4-dichlorophenoxyacetic acid dimethylammonium (2,4-DMA) salts were examined after single oral and mid-dorsal skin applications of the herbicides to male rats. Doses of 2.6 mg 2,4-D/kg body wt (sodium 2,4-D) and 1.9 mg 2,4-D/kg body wt (2,4-DMA) were applied. Quantitatively, with both salts, most of the orally administered herbicide (over 90%) was excreted in urine within 28 h. However, 2,4-D urinary peak concentrations were measured 4.5 and 20.5 h after dosing with 2,4-DMA and sodium 2,4-D, respectively. Additionally, the volume of urine in the oral study was significantly increased with both salts when compared with the controls or the dermal exposure. After topical application, 2,4-D absorption was much lower than in the oral study. Urinary excretion only reached about 10 and 15% of the applied dose for sodium 2,4-D and 2,4-DMA, respectively, by 5 days post-treatment. Further, we found some elevations in hepatic cytochrome P-450 activities. Ethylmorphine N-demethylase was only slightly induced by the herbicides while ethoxyresorufin O-deethylase activity was increased nearly 2-fold by sodium 2,4-D.
Knopp
D
D
Institute for Water, Soil and Air Hygiene of the Federal Health Office, Research Department Bad Elster, Federal Republic of Germany.
Schiller
F
F
D015084:2,4-Dichlorophenoxyacetic Acid / Q000493:pharmacokinetics* / Q000494:pharmacology; D000279:Administration, Cutaneous; D000284:Administration, Oral; D000818:Animals; D003577:Cytochrome P-450 Enzyme System / Q000096:biosynthesis / Q000187:drug effects; D004123:Dimethylamines / Q000493:pharmacokinetics* / Q000494:pharmacology; D004790:Enzyme Induction; D006540:Herbicides / Q000493:pharmacokinetics* / Q000494:pharmacology; D007408:Intestinal Absorption; D008099:Liver / Q000187:drug effects / Q000201:enzymology*; D008297:Male; D006899:Mixed Function Oxygenases / Q000096:biosynthesis* / Q000187:drug effects; D051381:Rats; D011919:Rats, Inbred Strains; D012869:Skin Absorption
D004123:Dimethylamines; D006540:Herbicides; C037991:2,4-D amine; D015084:2,4-Dichlorophenoxyacetic Acid; D003577:Cytochrome P-450 Enzyme System; D006899:Mixed Function Oxygenases