Summary (1995-2000)

The central theme of this research program is the development of peripheral biomarkers to assess toxicological effects of exposure to hazardous waste chemicals. The hypothesis centers on the idea that readily accessible body fluids and/or physiological functions provide biomarkers which may be predictive of exposure, adverse effects, and/or unusual susceptibility to toxic substances in the environment. Encompassed in the program are ten research projects; six biomedical, four nonbiomedical, and three support cores.

The biomedical projects can be grouped into two integrated subprograms. One subprogram is aimed at the development of biochemical and molecular biomarkers of exposure, effect, and susceptibility. In this area of research, one project is investigating the use of glutathione and glutathione biosynthesis as an integrative biomarker of oxidative stress. Another project is validating the efficacy of urinary porphyrin profile measurements as a biomarker of mercury (Hg) exposure, mercury-induced neurobehavioral effects, and mercury body burden in human subjects. Research is also being conducted to determine if fingerprints of P450 gene products can be used as biomarkers of exposure and/or susceptibility.

The other biomedical subprogram emphasizes the advancement of effects related biomarkers in human dosimetry and epidemiology. One project is evaluating physiologically based pharmacokinetic modeling of inter-individual differences in absorption, metabolism, and excretion of alklybenzenes in humans following controlled inhalation exposures. Another project consists of a case-control ecogenetic epidemiology study to assess whether oxidative stress from environmental pollutants is a risk factor for Parkinson's disease. In a third project, using an occupationally exposed cohort, researchers are analyzing the neurobehavioral, neurophysiologic, and neurobiochemical biomarkers of central nervous system dysfunction effects that may be attributed to styrene exposure.

Two nonbiomedical projects focus on developing biological approaches to remediation. Of these, one is exploring the use of natural and genetically altered higher plant species to degrade trichloroethylene and other chemicals found at hazardous waste sites. The other project is investigating the development of biological treatment systems to remove chlorinated organic compounds from groundwater. There are also two projects that focus on effects related biomarkers for ecological impact assessment. One is examining the use of wildlife as biomarkers of exposure to toxic substances. The other is measuring oxidative DNA damage as a biomarker of adverse ecological impact in fish exposed to contaminated sediments at a Superfund site in Puget Sound.

An important feature of this program is the interdisciplinary, cross project interactions that have been fostered by the SBRP structure. For example, methods developed to measure specific urinary porphyrins in mercury-exposed humans (Project 2) are effectively being used as biomarkers of mercury exposure in wildlife living near hazardous waste sites (Project 7). Likewise, new methods designed to measure genetic polymorphisms of chemical metabolizing enzymes (Project 4) have been put to use in human populations as potential biomarkers of susceptibility for Parkinson's Disease (Project 11) and exposures to aromatic hydrocarbon solvents (Project 10). The wildlife toxicology group (Project 7) has been helping the plant bioremediation team (Project 5) assess the potential toxicity to detritivores of poplar leaves used in remediation of TCE-contaminated ground water.

The individual projects are supported by administrative, training, and bioanalytical cores. The training core provides broad based educational opportunities and focuses on training new scientists to deal with the multidisciplinary aspects of hazardous waste problems. Collaborating institutions include Texas Tech University, Pacific Northwest Research Foundation, Batelle-Seattle Research Center, and Group Health Cooperative of Puget Sound.