Toxicokinetics and Bioavailability of Paraquat in Rats following Different Routes of Administration

Abstract

The toxicokinetics and bioavailability of[14C]paraquat were examined in rats which had received a single dose (11.6 μg/kg) of the herbicide by the iv, intragastric, dermal or pulmonary route. In the pulmonary route studies, rats were exposed to an aqueous solution or liquid aerosols of[14C]paraquat through a tracheal cannula or [14C]paraquat aerosols in a nose-only inhalation chamber. After intratracheal, intragastric, and dermal administration of[14C]paraquat to the rat, the average bioavailabilities were 0.45 ± 0.22, 0.12 ± 0.03, and 0.038 ± 0.027, which corresponded to 20.3 nmol, 5.4 nmol and 1.7 nmol of[14C]paraquat, respectively. Since the dose administered to the rat in the [14C]paraquat aerosol studies was unknown, the bioavailability for this exposure route could not be determined. However, about 27.5 nmol of[14C]paraquat was absorbed into the systemic circulation of the rat after inhaling [14C]paraquat aerosols through a tracheal cannula. [14C]paraquat administered to the rat iv was eliminated from the blood with a half-life of about 68 min. Urine and feces were the major excretion routes. The radioactivity absorbed into the systemic circulation of the rat was approximately equal to that excreted in the urine; about 23.8 nmol, 8.5 nmol and 1.5 nmol of[14C]paraquat were recovered from the urine of the rat after inhalation of[14C]paraquat aerosols in a nose-only exposure chamber, intragastric injection and dermal absorption of [14C]paraquat, respectively. Tissue distribution studies showed that the bulk of the [14C]paraquat administered to the rat by the inhalation and dermal routes remained at the sites of administration.