Molecular toxicology

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Human activities, such as fossil fuel consumption and metal mining, have caused the environment to be increasingly contaminated with environmentally persistent toxic heavy metal and metalloid compounds. The anthropogenic emissions of these pollutants are likely to increase even further as populous countries, such as India and China will increase their fossil fuel consumption in order to improve their standard of living. The resulting exposure of humans to increasing dietary levels of inorganic and organic forms of arsenic, cadmium, lead and mercury is therefore of much public concern. Toxicological studies have addressed the exposure of humans to these pollutants by studying the effect of single metals and metalloids in animals and have provided us with valuable data concerning their acute toxicity, such as the mechanism of toxicity and the mammalian target organs. Considerably less, however, is known about the molecular basis of the chronic toxicity and carcinogenicity of toxic metals and metalloid compounds in mammals. This must be attributed to the fact that biotransformations that occur after the absorption of a particular toxic metal or metalloid compound into the blood stream are poorly understood. Applying two advanced spectroscopic techniques, we will structurally characterize hitherto unknown metal and metalloid-containing metabolites which are formed in blood and are critically involved in the chronic toxicity of metals and metalloids and may be involved in human diseases, such as Parkinson's Disease and autism.This approach will allow us to better define the effect of multiple metal and metalloid exposure on human health. In addition, this research will reveal important mammalian detoxification mechanisms which are the key to develop a treatment against the chronic toxicity of metals and metalloid compounds which currenty affects millions of people.