Since very early in the history of medicine, laypersons and medical professionals have pondered over the etiology of disease. Excessive exposure to exogenous agents such as drugs, water, food, or airborne agents led to the hypothesis that the basic chemical or contaminant properties of these agents, coupled with host factors and body burden, may be responsible for disease etiology or progression in some diseases. This hypothesis has fueled the perpetual refinement of the scientific discipline of toxicology along with the problem of optimal determination of risk.