Goals
The major theme of the Superfund Basic Research Program (SBRP) at Texas A&M University is to conduct fundamental research studies to reduce the uncertainty associated with risk assessment of complex mixtures, and to improve scientific and public confidence in the overall risk assessment process. In order to achieve this goal, the Texas A&M SBRP will consist of four major Research Focus Areas (Table 1), that will be supported by facility cores and an Outreach Core to communicate research results to the general public.
Table 1. Summary of research focus areas and for SBRP at Texas A&M University.
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BASIC TOXICOLOGICAL RESEARCH
The Basic Toxicological Research Area, (Projects 1-4) will involve basic toxicological studies to investigate the molecular mechanisms of endocrine disruption, genotoxicity and non-genotoxic endpoints (i.e., nephrotoxicity and neurotoxicity) associated with many of the important classes of chemicals routinely identified in contaminated media at Superfund sites. In addition, animal studies will be conducted with model compounds and mixtures to investigate the influence of sensitive genotypes on chemical-induced toxic/genotoxic responses.
EXPOSURE ASSESSMENT AND MODELING
The Exposure Assessment and Modeling Research Area, (Project 6) will identify the major contaminants in three study areas, model transport and uptake of toxic chemicals to wildlife or human receptors, and investigate bioavailability of complex mixtures. The results of modeling conducted as a part of Project 6 will be used to define environmentally relevant doses for evaluation in Projects 1 – 3.
SITE REMEDIATION
The Site Remediation Research Focus Area, will develop new methods to utilize chemical intervention technologies for remediation of contaminated media (Project 5). Studies will also be conducted to develop improved techniques for utilizing and evaluating natural attenuation and other biological techniques for reducing the toxicity of contaminated media (Projects 6). The product of these three research focus areas will be an improved understanding of the mechanisms of complex mixture toxicity, as well as preliminary information to predict the fate and transport of contaminants from environmental media to an exposed receptor.
POPULATION STUDIES
The Population Studies Research Focus Area, (Projects 6) includes population studies to integrate results from Projects 1 through 6 for the purpose of defining exposure levels that are likely produce an adverse effect. Data from environmental monitoring will be applied to models to estimate exposures. Contaminant levels in wildlife tissue will be used to validate those models. Finally, retrospective and prospective cohort studies will be conducted to investigate adverse birth outcomes in an exposed population.
The proposed research program integrates basic toxicological studies to define the mechanism's of action and dose-response relationship of mixtures with engineering studies to predict the efficacy of remedial procedures or estimate the dose of exposure from a contaminant release; and, population studies to investigate the frequency of adverse effects in an exposed population. The combined product of the program project will reduce uncertainty in the toxicity assessment, exposure assessment, and risk characterization phases of the standard risk assessment methodology.
The Texas A&M SBRP will consist of six research projects, four support cores and an Outreach Core. A summary of the proposed integrated research program is illustrated in Figure 1 and takes advantage of the results of long term research activities within this SBRP that have focused on development and standardization of bioassays (in vitro and in vivo) for hazard and risk assessment of complex mixtures. The program illustrated in Figure 1 is designed to: (1) model potential exposures and identify specific Contaminants of Concern (COCs) in various environmental media; (2) conduct a series of in vitro and in vivo bioassays to evaluate the effects of potential exposure doses and chemical interactions under controlled conditions; and, (3) monitor the effect of exposures in wildlife (continuous exposures of minimal variability) and human (discontinuous exposures of significant variability) populations. Ongoing environmental monitoring and surveillance of various sites (Project 6) has identified complex mixtures of polynuclear aromatic hydrocarbons (PAHs), halogenated aromatic hydrocarbons (HAHs), industrial by-products and endocrine-active chemicals such as bisphenol A. These chemicals are typically identified in most Superfund sites and both PAHs and HAHs are among the most important classes of chemical contaminants in the global ecosystem (ATSDR, 1998; USEPA, 1998).
Figure 1. Overall integration of four research areas of Texas A&M SBRP.
The proposed program project includes four basic toxicological studies and two engineering studies. Endocrine disruptors will be the focus of Project 1. This project will conduct a series of in vitro studies to investigate the estrogenic activity of both environmental contaminants and naturally occurring compounds. A tier of four tests will be utilized to investigate the genotoxic potential of model compounds and complex mixtures (Project 2). This project will continue efforts to isolate and identify the most toxic components of complex mixtures, as well as to investigate potential genotoxic interactions. Non-genotoxic endpoints, including neurotoxicity and nephrotoxicity, will be investigated in Project 3. Non-invasive cellular imaging and functional analysis will be utilized to investigate both the site and the mechanisms of toxic injury. Project 4 will study the influence of sensitive genotypes on environmentally-induced orofacial clefts and neural tube defects.
Site remediation studies will encompass basic research on interactions of organic contaminants with modified clays (Project 5) and utilize clay-based and other chemical intervention technologies for field studies on site remediation (Project 6). In addition, natural attenuation of selected sites will be monitored utilizing bioassays during and after remediation to determine the efficiencies of various technologies. Development of biomarkers of exposure and adverse effects resulting from exposure to complex mixtures is linked to our understanding of basic mechanisms of toxicity that delineate tissue-specific actions of prototypical Superfund chemical mixtures and individual compounds. Therefore, the basic research activities (Projects 1-4) will address important fundamental questions regarding endocrine disruptors (focused on xenoestrogens), genotoxic and non-genotoxic responses induced by PAHs and animal models for determining susceptible genotypes. Results of these studies will be integrated with ongoing research in the other Research Foci.
Exposure assessment and modeling studies (Project 6) will also be conducted to improve methods for risk assessment of complex mixtures. Selected complex mixtures which are recovered from environmental samples will be extracted and fractionated to provide materials for study in the biological tests. Testing will be conducted in a battery of biological assays using model compounds, complex environmental mixtures, isolated fractions and reconstituted mixtures. The data from these studies will be used to develop toxicity values [i.e., Reference Dose (RfD) or Cancer Potency Slope (CPS), or Toxic Equivalency Factor (TEF)] for CoCs, and to investigate potential interactions of the components of complex mixtures. The major objectives of this section of the research will be to first identify the most toxic components of mixtures; and, to determine if compound interactions effect the toxicity of mixtures. This research will complement and extend results of previous studies by the PIs that have focused on interactions of COCs using model compounds and reconstituted mixtures.
Environmental surveillance and population studies (Projects 6) will be focused on three populated areas that contain a range of contaminants and contaminant levels. These will include petroleum contaminated areas in Baku, Azerbaijan, and the Wetlands Research Facility on the San Jacinto River in Channelview, Texas, as well as rural areas and colonies in the lower Rio Grande Valley in Texas (Table 2).
Table 2. Sites to be used in risk assessment research in TAMU-SBRP.
| Site | Contaminants of Concern | Population | Effect Studied |
| Baku, Azerbaijan, Sumgayit, Azerbaijan | Petroleum hydrocarbons Polycyclic hydrocarbons Metals (Hg, others) | Children | Birth defects Biomarkers of exposure |
| San Jacinto Wetland Research Facility | Petroleum hydrocarbons Metals | Wildlife | Biomarkers of exposure |
| Lower Rio Grande Valley | Pesticides Plasticizers and Metals | Wildlife | Biomarkers of exposure |
Miscellaneous Superfund sites: Libby Groundwater, Somers, MT, Atlantic Wood, Texarkana Wood, East Fork Poplar Creek, Other EPA-Cincinnati Sites |
PAHs, PCP PAHs PAHs, PCP PAHs, PCP Hg, Other organics PAHs, PCBs |
Site dependent | Site dependent |
The sites have been selected to include a primary site where environmental contamination is high and adverse effects on populations are likely (Baku, Azerbaijan); a site where contaminant levels and transport have been well characterized and monitoring contaminant concentrations in wildlife is likely to provide valuable data for exposure modeling (Channelview, TX); and, a site where contaminant levels and exposures are poorly understood so that the model can be tested (Rio Grande Valley, TX). Preliminary environmental surveillance studies have already been conducted in each of these areas to provide data to identify potential contaminants of concern. Results from the proposed studies at these sites will be used to develop models for predicting chemical exposures for adjacent receptors. Additional Superfund sites will also be used to validate exposure models and to provide field sites for remediation studies.
The basic toxicology, environmental surveillance and population studies will be designed to provide an understanding of the molecular mechanisms of complex mixture toxicology. The research will focus primarily on the different chemical classes which constitute the HAHs and PAHs, and will also include additional model chemicals as appropriate for the various toxic endpoints. Research will determine congener effects, interactions associated with mixtures, chemical and bioremediation degradation techniques and novel methods for exposure and site assessment. The individual projects will involve extensive collaboration between the different research groups and the results will be utilized to reduce the uncertainty associated with complex mixture risk assessment. A summary of the integrated nature of the various individual projects and cores is provided in Figure 2.
