Associate Professor Robert Mead

Room: BioSc/3.023

Research

Toxicology and metabolism of fluorinated pesticides particularly fluoroacetate and 1,3 difluoro-2-propanol. Development of antidotes to combat accidental ingestion of toxins. Mode of toxic action of plant secondary compounds particularly in relation to plant-animal interaction.

Projects

Metabolism and Toxicology of the Pesticide, Gliftor

Gliftor is a pesticide currently used in the former USSR to control small rodents such as voles. It is a mixture of 70% 1,3 difluoro-2-propanol and 30% 3-chloro-1-fluoro-2-propanol. Our recent work has established that it is toxic because it is metabolised in the poisoned animal to fluoroacetate, a pesticide used in Australia to control rabbits. The toxicity of fluoroacetate is the result of its conversion into fluorocitrate which is a potent inhibitor of the TCA-cycle-enzyme, aconitase. We have determined that 1,3 difluoro-2-propanol is initially converted in the animal to difluoroacetone by an NAD+-dependent alcohol dehydrogenase and this metabolite is then converted to fluoroacetate and hence fluorocitrate. We have also established that the NAD+-dependent alcohol dehydrogenase is powerfully inhibited in vivo and in vitro by pyrazole, diethyldithio-carbamate and by 4 methyl pyrazole. These compounds, therefore, prevent the conversion of 1,3 difluoro-2-propanol to fluorocitrate and can function as effective antidotes in vivo, to combat accidental ingestion of the pesticide. The toxic properties and metabolic fate of the minor component of Gliftor (3chloro-1-fluoro-2-propanol) are unknown and are currently being investigated. Techniques to be employed will include citrate and fluoride assays; determination of aconitase and cytochrome P450 activity in kidney and liver homogenates and analysis of incubation mixtures by gas-liquid chromatography and mass spectrometry.

Projects

Opportunities exist for students to undertake Honours projects in clinical areas (e.g. clinical biochemistry, immunology, cancer research) at either Fremantle Hospital or QEII Medical Centre. Such projects are jointly supervised by A/Prof Mead and a hospital physician.

Contact A/Prof Mead for further information.

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