Although predictions for many processes are very reliable, there are large uncertainties in identifying reactive chemicals and estimating their inherent potency. Another major area of concern is the inability to systematically identify and quantify metabolic reactions. Failure to quantify these reactions can lead to toxicity predictions that underestimate hazards of xenobiotics by several orders of magnitude. Conversely, typical bioconcentration models, which assume no xenobiotic metabolism, can result in estimates that are overly conservative.
Research focuses on two major areas.
The first one addresses cellular and biochemical responses elicited by reactive chemicals. Through this effort, hypotheses are examined in order to understand modes of toxic action, appropriate dose metrics, and potential endpoints and response syndromes for QSAR development. The second area addresses investigations of metabolic activation and degradation reactions. The goals of these studies are to identify critical metabolic products and reaction rates, and to complement mechanistic and physiologically based toxicokinetic studies. The data will be integrated with QSAR and artificial intelligence research that addresses approaches to predict metabolic pathways and rates.