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Oregon Health and Science University

Superfund Research Program

Biomarkers of Neurotoxicant Exposure and Neurodegeneration

Project Leaders: Mohammad I. Sabri, Peter S. Spencer
Grant Number: P42ES010338
Funding Period: 2000-2006

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Project Summary (2000-2006)

Superfund sites commonly contain organic solvents with neurotoxic potential. These substances include aromatic hydrocarbons, such as benzene and toluene, and aliphatic hydrocarbons, such as 2-butanone (methyl ethylketone). Researchers are utilizing biochemical, analytical, and morphological methods, to test the following hypotheses: 1) a relationship exists between the structural and toxicological properties of 1,2- diacetyl benzene (1,2-DAB) and 2,5-hexanedione (2,5-HD), (2) the chromogenic and neurotoxic properties of 1,2-DAB are directly interrelated, (3) 1,2-DAB is the neurotoxic metabolic of 1,2-diethylbenzene (1,2-DEB), and (4) 2-butanone and toluene, which respectively enhance and suppress the neurotoxic potential of n-hexane by altering its metabolism to 2,5-HD, modulate the neurotoxic potency of 1,2-DEB by altering its metabolism to 1,2-DAB. The major goal of this research project is to determine if the urinary chromogen (known to form in humans as well as rodents) can be used as a sensitive and specific biomarker of exposure to aromatic hydrocarbons with neurotoxic potential. These results will help researchers to develop an ultra-sensitive biomarker of exposure to non-chlorinated organic solvents that can be used to identify individuals/populations at risk for neurotoxicity.

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