Absorption and Excretion of Diquat and Paraquat in Rats

Abstract

The fate of 14C-labelled diquat and paraquat after oral and subcutaneous administration of single doses has been studied in the rat. By both routes of administration the radioactivity usually appears in the excreta within two days. In a few cases a small amount is excreted in the urine on the third day or in faeces on the fourth day. After an oral dose of paraquat no radioactivity could be detected in bile, and with diquat less than 5% of the dose appeared in bile within 24 hours. Both diquat and paraquat are poorly absorbed from the gut, and after subcutaneous administration little or none appears in faeces.By comparison of the measurements of radioactivity with a specific chemical test for diquat and paraquat, the presence of a small amount of metabolites in the urine after oral dosing has been detected. As no such metabolism has been observed after subcutaneous administration it seems probable that there is some absorption of degradation products formed within the gut. It has been shown that about 70% of an oral dose of diquat and about 30% of a dose of paraquat is present in faeces as metabolic products. In vitro experiments have shown that this is probably due to microbiological degradation in the gut.Diquat and paraquat are bipyridilium compounds which have been developed as herbicides and desiccants under the trade names 'Reglone' and 'Gramoxone' respectively (Calderbank and Crowdy, I962). Their structural formulae are indicated below; they are usually supplied as the dichloride, dibromide or dimethosulphate salts. Both can be reduced to coloured free-radicals, and paraquat has been known for many years as the oxidation-reduction indicator methyl viologen. +N

Two autopsy cases of paraquat poisoning.

“…It is poorly absorbed from the gut. The bulk of an oral dose is found in feces, whereas after subcutaneous dose, most of it is found in the urine and little or none in the feces (Daniel and Gage 1966).…”

Biliary excretion of some diquaternary ammonium cations in the rat, guinea pig and rabbit

“…Studies on the metabolism of all these compounds, except morfamquat, have been reported in the literature. Daniel & Gage (1966) found only unchanged paraquat and diquat in the urine of intact rats given these compounds subcutaneously, and decamethonium has been reported to be excreted unchanged in the urine by rabbits (Broen Christensen, 1967), cats (Luthi & Waser, 1965) and humans (see Paton & Zaimis, 1952). Dimethyltubocurarine labelled with 14C in four of its methyl groups has been examined by Marsh (1952), whose results suggest that the compound is largely excreted unchanged in the urine after injection into guinea pigs, but when injected into rats the compound is excreted in the urine largely as unidentified metabolites, with a small amount of 14C appearing in the expired air in an unidentified form.…”

“…The amount of [14C]diquat or [(4C]paraquat in the eluate from the column was determined both from the '4C content of portions (0.2ml) of the eluate and by colorimetric analysis as described by Daniel & Gage (1966).…”

“…[14C]Diquat or [14C]paraquat was separated from urine samples by column chromatography on a cation-exchange resin (Dowex 5OW, X8; British Drug Houses, Poole, Dorset, U.K.; 1 ml of resin was used to prepare a column of 5mm internal diameter) essentially as described by Daniel & Gage (1966). The amount of [14C]diquat or [(4C]paraquat in the eluate from the column was determined both from the '4C content of portions (0.2ml) of the eluate and by colorimetric analysis as described by Daniel & Gage (1966).…”

Paraquat, Between Apoptosis and Autophagy

“…When rats ingested toxic amounts of PQ (either accidentally or voluntary), the initial absorption occurred in the small intestine where the amount absorbed by the stomach was negligible, especially if there was parallel food intake, and the majority was excreted in the urine and feces (Daniel & Gage, 1966). It can also be absorbed and causes damage when it contacts with the skin, especially when there was a previously damaged area that would cause an abrasion contact zone (J. G. Smith, 1988).…”