1 Introduction to Mixtures Toxicology and Risk Assessment

When humans are exposed to chemicals, they are not exposed to just one chemical at a time. A vast number of chemicals pervade our environment. Exposures, whether simultaneous or sequential, are to chemical mixtures. The standard definition of a chemical mixture is any set of multiple chemicals regardless of source that may or maynot be identifiable thatmay contribute to joint toxicity in a target population [1, 2]. By some estimates, up to 6 billion tons of waste is produced annually in theUnited States. Several years ago, the US Office of Technology Assessment estimated 275 million of those tons were hazardous. Most waste finds its way to more than 30 000 toxicwaste disposal sites across theUnited States, amajority ofwhich theUSEPAhas categorized as uncontrolled hazardous waste sites [3]. Thus far, traditional risk assessment, even with its inherent shortcomings, has helped to control chemical exposures to that waste reasonably well, as evidenced by statistics on longevity, health status, and world population growth. Yet, new health and environment indicators have raised disquieting questions, and a consequent growing concern is that this success might be short-lived. One reason is an alarming, logarithmic increase in the synthesis, manufacture, and use of chemicals worldwide as “developed” and “developing” countries compete to provide their populations an improved quality of life. Tohelpmeet these concerns, theWorldHealthOrganization (WHO), as part of its harmonization of approaches project, recently published a report onmethods and approaches for risk assessment of chemical mixtures [4, 5]. Former US Secretary of Defense Donald Rumsfeld once said with regard to intelligence reports