Disposition of 2,4‐dichlorophenoxyacetic acid dimethylamine salt by fischer 344 rats dosed orally and dermally

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Abstract
The dimethylamine salt of 14 C‐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 14 C‐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.

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