AbstractThe design of new materials can be made more efficient if toxicity screening is performed in early rather than in late stages of development, especially for volatile materials such as lubricants, fire retardants, fuels, and fuel additives. In our continuing efforts to develop methods for the prediction of the toxicological response to materials of interest to the U.S. Air Force, we have constructed Quantitative Structure-Activity Relationships (QSARs) for thirteen newly proposed propellant compounds. We employed two previously published in vitro toxicity endpoints in primary cultures of isolated rat hepatocytes, which measured decrease in mitochondrial function and glutathione depletion [1]. Molecular descriptors were obtained using ab initio molecular orbital theory. QSAR models were then derived for each endpoint. Correlation coefficients for 2- and 3-parameter QSARs exceed 0.9, possibly enabling toxicity predictions for similar compounds. Insight into the biophysical mechanism of toxic response can be gained from interpretation of the descriptors comprising the QSARs.
Risk Assessment of High-Energy Chemicals by in Vitro Toxicity Screening and Quantitative Structure-Activity Relationships