The long-term goal of this project is to formulate Innovative risk assessment methodologies on chemical mixtures by coupling physiologically based pharmacokinetics/pharmacodynamics (PB-PK/PD) and other experimental toxicology with statistical/mathematical modeling such as isobolographic analysis and response surface methodology. The central questions to ask are: (1) How should we handle chemical mixtures and toxicologic interactions?; (2) Can we develop """"""""Predictive Toxicology"""""""" for chemical mixtures:/ (3) How may we incorporate state-of-the art science into the risk assessment process, particularly for chemical mixtures? To answer and to address these questions, we propose to use two approaches, the """"""""Bottom- Up"""""""" and """"""""Top-Down"""""""" approaches. The """"""""Bottom-Up"""""""" approach refers to systematic toxicologic interaction studies starting with binary chemical mixtures based on toxic mechanism(s). A third, fourth,....chemical is then added based on mechanistic considerations and, in this way, we build up the chemical mixtures. In this project, for the """"""""Bottom-Up"""""""" approach, we intend to study toxicologic interactions of Kepone and CCI based on the mechanistic concept that Kepone impaires tissue repair. The """"""""Top-Down"""""""" approach, on the other hand, will start out with the chemical mixture of 4 groundwater contaminants (arsenic 1,2-dichloroeethane, trichloroethylene, and vinyl chloride. We will then systematically conduct toxicology experiments on organic and inorganic submixtures, component until we get to individual chemicals. Throughout these experiments, PB-PK/PD modeling coupled with isobolographic analysis and response surface methodology will be used to achieve the goal of """"""""Predictive Toxicology.""""""""

Project Start
1999-04-01
Project End
2001-12-31
Budget Start
1998-10-01
Budget End
1999-09-30
Support Year
8
Fiscal Year
1999
Total Cost
Indirect Cost
Name
Colorado State University-Fort Collins
Department
Type
DUNS #
112617480
City
Fort Collins
State
CO
Country
United States
Zip Code
80523
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
Chubb, Laura S; Andersen, Melvin E; Broccardo, Carolyn J et al. (2004) Regional induction of CYP1A1 in rat liver following treatment with mixtures of PCB 126 and PCB 153. Toxicol Pathol 32:467-73
Ou, Ying C; Conolly, Rory B; Thomas, Russell S et al. (2003) Stochastic simulation of hepatic preneoplastic foci development for four chlorobenzene congeners in a medium-term bioassay. Toxicol Sci 73:301-14

Showing the most recent 10 out of 56 publications