Disposition of 2,4-dichlorophenoxyacetic acid dimethylamine by Fischer 344 rats dosed orally and dermally.
The dimethylamine salt of 14C-ring-labeled 2,4-D was administered to Fischer 344 rats orally (1 and 0.4 mg/kg body weight) and dermally (10 mg/kg body weight). Absorption, distribution, and elimination were determined from 14C-labeled 2,4-D in blood, tissues, and excreta. Quantitatively, most of the orally administered dose (94-96%) became systemically available within 6 h. Following dermal administration 10% of the dose became systemically available over 72 h. However, peak concentrations in blood and kidneys were achieved within 30 min of dosing by either route. By 1.5 h after dosing, 2,4-D concentrations in blood, muscle, liver, and kidneys had decreased in both the orally dosed and dermally dosed animals. Between 2 and 8 h, the blood, muscle, liver and kidney concentrations in dermally dosed animals maintained a plateau while urinary excretion increased, presumably due to continued absorption of 2,4-D from the skin. The concentrations in orally dosed animals continued to decrease. Following 7 h of dermal exposure, skin cleansing removed about 63% of the applied dose; about 17% of the applied dose remained at the site of dermal dosing. At 8 h, 2,4-D concentrations in blood, muscle, liver, and kidneys of dermally dosed animals began to decrease, most likely a result of the removal of the reservoir on the skin. However, 2,4-D continued to be absorbed from skin site, resulting in a slower decline of the 2,4-D concentrations in these tissues over remainder of the 72-h study period. By comparison, in animals that had been orally dosed, the absorbed dose was almost completely excreted within 24 h.
Pelletier
O
O
Pesticides Division, Environmental Health Centre, Ottawa, Ontario, Canada.
Ritter
L
L
Caron
J
J
Somers
D
D
D015084:2,4-Dichlorophenoxyacetic Acid / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D000284:Administration, Oral; D000287:Administration, Topical; D000818:Animals; D002250:Carbon Radioisotopes / Q000378:metabolism; D004123:Dimethylamines / Q000493:pharmacokinetics; D008297:Male; D051381:Rats; D011916:Rats, Inbred F344; D013997:Time Factors; D014018:Tissue Distribution
D002250:Carbon Radioisotopes; D004123:Dimethylamines; D015084:2,4-Dichlorophenoxyacetic Acid