Interdisciplinary and Alternative Approach to Assess Carcinogenicity ofChlorobenzenes

摘要

The objective of this research project is to create an interdisciplinary approachin 'Predictive and Alternative Toxicology,' based on the integration of mechanistic toxicology and computer-based modeling systems I.E., PHYSIOLOGICALLY BASED PHARMACOKINETIC/PHARMACO DYNAMIC (PBPK/PD) models for kj evaluation of carcinogenic activity of selected chlorobenzene isomers. The research project focuses on four of the 12 chlorobenzene isomers: 1,4-dichlorobenzene (DCB), 1,2,4,5-tettrachlorobenzene (TeCB), pentachlorobenzene (PeCB), and hexachlorobenzene (HCB). Using a variety of techniques in experimental toxicology, biochemistry, and molecular biology, a great knowledge of the roles of cell division, cell death, and mutation in relation to chemically induced cancer is achieved. Furthermore, the development of biologically based cancer models will reduce uncertainty in estimating the carcinogenic risk in humans from long-term exposure to chemical carcinogens and gain headway in the area of low dose extrapolation. The long-term goal is to formulate an overall approach to predictive carcinogenic potential of chemicals where animal usage is reduced; the lengthy experimental duration is shortened; and resource requirement is minimized.