Toxic Characteristics of Fluorocitrate, the Toxic Metabolite of Compound 1080

This paper reviews toxicological research involving fluorocitrate, the toxic metabolite of sodium monofluoroacetate (fluoroacetate), which is the active ingredient in the pesticide Compound 1080. Many toxicological studies have been done with fluoroacetate and the results obtained are actually due to the fluorocitrate because it has been definitely proved that, from a biochemical perspective,fluoroacetate is not toxic but fluorocitrate is. The classical explanation of the toxic action of fluorocitrate is that it inhibits the enzyme aconitase in the tricarboxylic acid cycle. Deactivation of aconitase results in decreased energy production by cells and ultimately death of the organism. However, the more recent explanation of fluorocitrate's mode of action is that it binds with mitochondrial protein which prevents transport of citrate and its utilization by cells for energy production. Metabolism studies indicate that only small amounts, perhaps less than 3%, of fluorocitrate is formed from fluoroacetate. From the limited number of acute and chronic studies conducted with fluorocitrate it does not appear to be as potent as fluoroacetate by either the oral or parenteral routes of administration. This decreased level of toxicity is thought to be due to the larger molecular weight of fluorocitrate which would not be as readily absorbed by tissues. Central nervous system toxic manifestations (i.e., tremors, convulsions) are characteristic in many animals poisoned with fluoroacetate. Fluorocitrate administered directly into the brain was found to be 100 times more toxic than fluoroacetate. The accumulation of citrate in organs is characteristic of fluorocitrate poisoning; from a quantitative point of view the liver is less affected than the brain, heart, kidney, or spleen. Fluorocitrate causes extensive kidney damage, but the testes are most sensitive to sublethal doses. Testicular damage may be either reversible or irreversible, depending upon the dose. Several plants have the ability to metabolize both fluoroacetate and fluorocitrate from either inorganic or atmospheric fluoride.