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.

Absence of P-Glycoprotein Transport in the Pharmacokinetics and Toxicity of the Herbicide Paraquat

“…The paraquat plasma concentrations we observed following an oral dose in FVB mice were approximately a magnitude less than what has been observed following an intraperitoneal dose to C57BlJ/6 mice; correspondingly, the paraquat brain concentrations we observed were also lower (Prasad et al, 2007(Prasad et al, , 2009Breckenridge et al, 2013). Paraquat has highly variable bioavailability depending upon the route of administration, with the majority of an oral dose found in the feces, which may explain some of the differences in observed plasma concentrations in the different mouse strains (Daniel and Gage, 1966;Chui et al, 1988). …”

Prolonged Toxicokinetics and Toxicodynamics of Paraquat in Mouse Brain

“…Other studies using radiolabeled PQ found that it was absorbed by all exposure routes tested, including intravenous, intragastric, dermal, and pulmonary (Chui et al 1988; Dey et al 1990). PQ in brain after oral dosing was previously demonstrated in rat and the concentration was higher after 10 doses compared with 1, supporting its accumulation (Widdowson et al 1996).…”

Homicidal Paraquat Poisoning

“…Wearing PQ‐soaked underwear would cause prolonged exposure to PQ, which might partly explain the high concentration of PQ in cardiac blood. PQ distribution in the postmortem tissues could be related to many factors, such as the time between exposure and death , the route of exposure , and the medical treatment . To better understand the distribution characteristics of PQ in humans, more human data are needed.…”