Developing Dose Response Assessment Methods for Endocrine Active Compounds (EACs): Examples Based on Xenobiotics That Alter Normal Homeostatic Feedback Control Processes. M. E. Andersen and H. A. Barton, KS Crump Division, ICF Kaiser Engineers, Inc., PO Box 14348, Research Triangle Park, NC 27709
Endocrine active compounds (EACs) alter signaling processes responsible for regulation and co-ordination of physiological functions in the body during development and adulthood. Many endocrine-mediated regulatory processes involve modulatory (negative feedback) and activational (positive feedback) processes in their control repertoire. EACs have the potential to interfere with these control processes, leading to altered function and toxicity. Examples of EACs include natural hormones and their synthetic analogs, some compounds, such as phytoestrogens present in food, pharmaceuticals, and some industrial chemicals. The challenge with EACs is to move ahead in concert to develop new hazard identification methods for EAC and new quantitative tools to evaluate the expected shape of dose response curves at low doses. In general, the determination of the low dose behavior will depend in large part on unraveling the behavior of the control mechanisms for the function of the natural hormones. This presentation focuses on positive and negative feedback involved in homeostatic control of normal physiological function and examines interactions of several xenobiotics with these control systems in the body. Two responsible for regulation and co-ordination of physiological functions in the body during development and adulthood. Many endocrine-mediated regulatory processes involve modulatory (negative feedback) and his activational (positive feedback) processes in their control repertoire. EACs have the potential to interfere with these control processes, leading to altered function and toxicity. Examples of EACs include natural hormones . . . . . . [RiskWorld Note: Submitted abstract incomplete]