Exposure to combinations of substances: a system for assessing health risks.

Combined exposures may be categorised as specified combinations or mixtures of substances, depending on composition and exposure scenario. The major characteristic of a specified combination is known composition and that of a mixture simultaneous exposure. A framework was developed as a guide for safety evaluation of combined exposures. This framework offers the possibility to evaluate mixtures as a single entity, or as a number of fractions or individual constituents. The evaluation of specified combinations will often focus on the individual components. To reduce the safety evaluation of complex exposures to manageable proportions, the "top n" and "pseudo top n" approaches were introduced, n representing the n most "risky" chemicals or groups of chemicals, respectively. To select the best method, the framework should always be walked through in its entirety, considering all options. The Mumtaz-Durkin weight-of-evidence approach is included as a prioritization instrument for combined exposures. It is based on hazard indices supplemented with qualitative and quantitative weighting and interaction factors.