Citation:

BENCIC, D. C., A. D. BIALES, AND J. M. LAZORCHAK. USING MOLECULAR INDICATORS FOR THE DETECTION OF EXPOSURE TO EMERGING CONTAMINANTS. Presented at SWIMS Conference, Chicago, IL, January 30 - February 01, 2007.

Impact/Purpose:

The indeterminate condition of exposure indicator research stands to change markedly with the ability to connect molecular biological technologies with cellular or tissue effects and outcomes. Three focal areas of ecological research aim to develop a sequence of approaches where "the earliest recognizable signatures of exposure" (i.e., unique patterns of up- and down-regulated genes and proteins) are identified for numerous stressors, demonstrable in case studies and incorporated into Agency, State and Regional studies supported by EMAP and other programs.

Area 1, Computational Toxicology Research: Exposure assessment has historically been based on use of chemical analysis data to generate exposure models. While biological activity of chemicals has been recognized to be important for exposure risk assessments, measurement of such activity has been limited to whole organism toxicity tests. Use of molecular approaches will:

improve extrapolation between components of source-to-outcome continuum (source , exposure , dose , effect , outcome)

Using a systems modeling approach, gene and protein expression data, in small fish models (fathead minnow and zebrafish), will be integrated with metabolomic and histopathological data. This will assist in prediction of environmental transformation and chemical effects based on structural characteristics, and enhance quantitative risk assessments, including areas of uncertainty such as a basis for extrapolation of effects of endocrine disrupting chemicals, interspecies extrapolation, complex chemical mixtures and dose-response assessment.

Area 2, Ecological Research-Environmental Diagnostics: Development of molecular diagnostic indicators contributes to several of the GPRA Diagnostic Research Goals. Methods will employ DNA microarray technology and expression proteomics, focusing on species of relevance to aquatic ecosystem risk assessment. Significantly, these diagnostic indicators will open the door to understanding subcellular interactions resulting from exposure to complex chemical mixtures.

define relationship between genetic disposition of populations and degree/specificity of stressor-specific gene transcriptional response in aquatic organisms (fish and invertebrates)

identify of chemical mixture induced transcriptional "patterns" using microarrays and hyperspectral scanning - via collaboration with DOE Sandia National Labs

apply molecular indicators to watershed level stressor study, including pilot studies with targeted pesticides and toxins indicators

develop molecular indicators of exposure for invertebrates (Daphnia, Lumbriculus, Chironomus)

Area 3, Exposure Research in Endocrine Disruptors:

Subobjective 1: Develop exposure methods, measurement protocols, and models for assessment of risk management practices of endocrine disrupting compounds. As risk management approaches are identified and developed, there will be a need to identify, adapt and develop bioassay screening tools and other analytical methods to assess their efficacy. Measurements research will be performed to define management needs. This effort will entail cross-lab participation from NRMRL, NERL and NHEERL.

Subobjective 2: Determine extent of environmental and human exposures to EDCs, characterize sources and factors influencing these exposures, develop and evaluate risk management strategies to reduce exposures. In order to develop effective risk management strategies, it is important to understand the extent of exposures to endocrine disrupting compounds and factors influencing source-to-exposure-to-dose relationships.

apply molecular indicators of exposure to estrogenic compounds in selected wastewater treatment plants located in ten USEPA Regions

identify differential gene expression following exposure of fathead minnows to environmental androgens and androgen-like compounds

apply molecular indicators of exposu

Description:

Aquatic organisms are constantly exposed to complex combinations of natural and anthropogenic stressors. These stressors have been linked to many biological effects in aquatic vertebrates and have the potential to result in population level effects. The overall fate, as well as, the nature and extent of ecological effects of these stressors remains poorly understood. Thus, there is a clear need for the establishment and validation of biologically-based indicators of chemical exposure in aquatic ecosystems. These indicators are often rapid, sensitive, highly specific, and integrate confounding factors such as exposure duration, biological availability, and multiple stressor interactions. Therefore, they can provide a more complete characterization of aquatic exposure when compared to other more traditional methods. Here, we overview several analytical molecular methods that target multiple sub-cellular biological levels. Additionally, we highlight current projects which use a combination of laboratory- and field-based experimental systems to provide molecular indicators of exposure that are robust to the highly dynamic and complex nature of real-world exposures. These projects use environmentally-relevant compounds which are representative of several chemical classes, such as endocrine disrupting compounds (EDCs), triazines, pyrethroids, and OP pesticides. Once identified and validated, these indicators may be incorporated into ongoing monitoring efforts with minimal additional effort and improve exposure modeling and enhance risk assessment of existing and emerging contaminants in the aquatic environment. Our goal is to transfer these molecular indicators to the Program Offices, Regions, States, and Tribes so that they can be used to assess the condition and vulnerability of the Nation's aquatic ecosystems.

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