Identification of an initial chemical set

The first model development step was to find a representative set of chemical compounds, which could be used in later stages of computer modeling. We selected a variety of substances, which have been previously shown to have a toxic effect on biological material. Our preliminary set was selected from ToxCast – EPA’s largest database evaluating toxicity of industrial and consumer products, food additives, and potentially “green” chemicals that could be safer alternatives to existing chemicals. Specifically, we wanted to concentrate on banned substances, industrial by-products and pesticides.

The selection criteria included the ability of chemicals to induce an Oxidative Stress (OS). Oxidative stress has been highly correlated with diseases such as immune suppression, cancer, aging, rheumatoid diseases, cardiovascular disease and Parkinson’s and Alzheimer’s diseases. Thus a focus on chemicals that lead to OS is strategic for addressing numerous human health endpoints. OS is implicated in the toxicity of many industrial chemicals through direct or indirect damage to DNA, RNA, proteins and lipids. Underlying mechanisms involve redox cycling of a xenobiotic or its metabolites which leads to amplified production of reactive oxygen species (ROS) and their downstream effects.

Selected compounds will be then used for a initial informing of the computer model.