The central theme for this Program Project is """"""""Biological and Chemical Interactions of Chemical Mixtures."""""""" Since the field of chemical mixture research is complex and still largely unexplored, the ultimate goal of this program is to incorporate state-of the-art science into human and ecological risk assessment methodologies for chemical mixtures as well as engineering remediation technology related to Superfund hazardous waste disposal sites. The various projects and cores will work in concert to attempt to: (1) determine target tissue dosimetry of chemicals under the condition of low-level, long-term exposure to chemical mixtures by coupling physiologically based pharmacokinetic/pharmacodynamic (PB-PK/PD) modeling, experimental toxicology, and statistical/mathematical modeling; (2) characterize interactive hepatotoxicity and hepatocarcinogenesis of chemical mixtures related to hazardous waste disposal; (3) establish molecular biomarkers for human exposure to environmental chemical mixtures; (4) develop invertebrate bioreporters for environmental pollution through molecular biology and molecular genetics technology; (5) define ecological impacts resulting from chemical mixture exposure related to Superfund hazardous waste sites; (6) develop engineering technologies for remediation of chemical mixture contaminated water. The proposed research will encompass both laboratory work on chemically defined mixtures of high priority hazardous waste substances and field work on and related to two Superfund sites in Colorado. Ultimately, this program should make significant contributions to innovative and efficient reduction of the amount and toxicity of hazardous wastes, preventing adverse human health effects, and minimizing ecological impact. This integrated program involves 17 different disciplines or specialties from 7 academic departments in 3 colleges plus collaborative scientists from outside o Colorado State University (CSU). The Program Project consists of 3 Cores (Administrative and Training, Analytical Chemistry and molecular Biology, and Spatial Information Analysis and Statistics) and 66 research Projects which are grouped under two Emphases. Under the Biomedical/Ecological/Epidemiological Emphasis, there ar three mechanistically-based toxicology projects (Project 1, PB-PK/PD Modeling; Project 2, Hepatocarcinogenesis; Project 3, Interactive Hepatotoxicity) and two molecular biology and ecology projects; Project 5, Molecular Genetic Bioreporting; Project 6, Mechanistic Ecological Evaluation; Under the Engineering Emphasis, there is one project Project 8, Environmental Biotechnology.

National Institute of Health (NIH)
National Institute of Environmental Health Sciences (NIEHS)
Hazardous Substances Basic Research Grants Program (NIEHS) (P42)
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Special Emphasis Panel (SRC (G1))
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Colorado State University-Fort Collins
Public Health & Prev Medicine
Schools of Veterinary Medicine
Fort Collins
United States
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Veeramachaneni, D N Rao (2012) Ultrastructural evaluation of semen to assess effects of exposure to toxicants. Toxicol Pathol 40:382-90
Zimbron, Julio A; Reardon, Kenneth F (2011) Continuous combined Fenton's oxidation and biodegradation for the treatment of pentachlorophenol-contaminated water. Water Res 45:5705-14
Lee, Sun Ku; Hamer, Dwayne; Bedwell, Cathy L et al. (2009) Effect of PCBs on the lactational transfer of methyl mercury in mice: PBPK modeling. Environ Toxicol Pharmacol 27:75-83
Veeramachaneni, D N Rao (2008) Impact of environmental pollutants on the male: effects on germ cell differentiation. Anim Reprod Sci 105:144-57
Yang, Raymond S H; Dennison, James E (2007) Initial analyses of the relationship between ""Thresholds"" of toxicity for individual chemicals and ""Interaction Thresholds"" for chemical mixtures. Toxicol Appl Pharmacol 223:133-8
Belfiore, Carol J; Yang, Raymond S H; Chubb, Laura S et al. (2007) Hepatic sequestration of chlordecone and hexafluoroacetone evaluated by pharmacokinetic modeling. Toxicology 234:59-72
Lee, Sun Ku; Ou, Ying C; Andersen, Melvin E et al. (2007) A physiologically based pharmacokinetic model for lactational transfer of PCB 153 with or without PCB 126 in mice. Arch Toxicol 81:101-11
Zimbron, Julio A; Reardon, Kenneth F (2005) Hydroxyl free radical reactivity toward aqueous chlorinated phenols. Water Res 39:865-9
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Bae, Dong-Soon; Handa, Robert J; Yang, Raymond S H et al. (2003) Gene expression patterns as potential molecular biomarkers for malignant transformation in human keratinocytes treated with MNNG, arsenic, or a metal mixture. Toxicol Sci 74:32-42

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