Observations upon the metabolism of fluorocitrate in rats

Abstract

Part 1. Reduced toxicity of fluorocitrate by the oral route in rats In contrast to the extreme toxicity of fluorocitrate inside mitochondria or the brain, growing rats were able to drink sublethal doses of the carbon fluorine compound for periods up to 7 months without harm ; the total dose so consumed was 6 times a lethal dose given by intraperitoneal injection. Part 2. The metabolism of fluorocitrate in the rat In an attempt to explain the reduced ' oral ’ toxicity using fluorocitrate labelled with 14 C in the 2 position, it was found that the mixed oxidase system in rat liver microsomes did not metabolize the 14 C moiety. When given by the intraperitoneal route, the labelled carbon was mainly excreted in the urine within 48 h. On the other hand, when non-labelled Na fluorocitrate (synthetic) was given to rats in a single oral dose, much inorganic fluoride was excreted together with citrate. Hence rat tissues can remove inorganic fluoride from fluorocitrate. This proof required a preliminary stabilization of the urinary excretion of inorganic fluoride on a special diet, as the ordinary rat pellets (41 B) may contain up to 20 parts/10 6 of inorganic fluoride.