Vehicle alteration of paraquat lethality in mice

Abstract

The lethal toxicity to mice of paraquat dissolved in saline was lower than when it was dissolved in distilled water. This was true whether paraquat was administered ip or sc. This apparent protective effect of saline was not observed when paraquat was given iv, or when saline was given by a different route concomitant with paraquat dissolved in water. The absorption of ip paraquat was apparently more rapid when water was the vehicle and significantly higher paraquat concentrations were observed in plasma, lung, and kidney 24 hr after injection. In untreated mice and those pretreated ip with paraquat in saline 24 hr earlier the decay of iv-administered paraquat from blood was slower when dissolved in water compared with saline. However, the disappearance of iv paraquat dissolved in saline or water was the same in mice that had been pretreated 24 hr earlier with ip paraquat dissolved in water. It is concluded that paraquat is more toxic dissolved in water because of a combination of increased absorption from the peritoneal cavity and decreased excretion at the later times after administration, thereby allowing higher concentrations of the herbicide to be accumulated in the lung.