Inter-individual variation in dose is a determinant of the significance of combined exposures to chemicals
All individuals are exposed to multiple chemicals from multiple sources. These combined exposures are a concern because they may cause adverse effects that would not occur from any single exposure. Studies of combined chemical exposures, however, have found that the risks posed by such combined exposures are almost always driven by exposures from a few chemicals and sources and frequently are driven by a single chemical from a single source. Here, a series of computer simulations of combined exposures are used to investigate when multiple sources of chemicals drive the largest risks in a population and when a single chemical from a single source is responsible for the largest risks. The analysis found that combined exposures drive the largest risks when: the interindividual variation of source-specific doses is small, moderate-to-high correlations occur between the source-specific doses, and the number of sources affecting an individual varies across individuals. These findings can be used to identify sources with the greatest potential to cause combined exposures of concern.