Some current approaches for studying combination toxicology in chemical mixtures

Using conventional toxicology methodologies and at the mode and rate of studying chemicals in the last 25 yr, it is doubtful that society will ever have adequate toxicology information on the majority of the chemicals we used now or in the future. Considering further the issue of health effects of chemical mixture exposure (i.e. real-world issues), the problem of not being able to obtain adequate toxicology information is amplified. From a different perspective, concerns over animal rights have raised the consciousness of many biomedical researchers regarding animal experimentation. As many as 17–100 million animals are estimated to be killed for biomedical research in the US alone each year; therefore, minimizing animal usage judiciously in toxicological research should be in the mind of every responsible toxicologist. From these considerations, it is apparent that new, alternative, less animal-intensive, shorter-term and less expensive toxicology methods must be developed if there is to be a reasonable chance to deal with the hundreds of thousands of chemicals, as well as the near-infinite number of chemical mixtures, in the environment. Some of the recent advances indeed are heading towards that direction. In this article, a number of approaches for research work on combination toxicology of chemical mixtures are given; the examples are selected based on one or more of the following criteria: (1) minimizing animal usage; (2) shortening experimental durations; (3) studying environmentally realistic concentrations; (4) utilizing statistical/mathematical modelling; (5) advancing efficient experimental designs and (6) developing predictive toxicology.