Environmental Risk Assessment of Pharmaceutical Mixtures: Demands, Gaps, and Possible Bridges

Abstract

The ecotoxicological risk of pharmaceutical mixtures typically exceeds the risk of each individual compound, which calls specific attention to the fact that monitoring surveys routinely find complex pharmaceutical mixtures in various environmental compartments. However, although the body of evidence on the ecotoxicology of pharmaceutical mixtures is quite consistent, the current guidelines for the environmental risk assessment of pharmaceuticals often do not explicitly address mixture effects. Data availability and acceptable methods often limit such assessments. A tiered approach that begins with summing up individual risk quotients, i.e., the ratio between the predicted or measured environmental concentration and the predicted no effect concentration (PNEC) is therefore suggested in this paper, in order to improve the realism of the environmental risk assessment of pharmaceuticals. Additionally, the use of a mixture-specific assessment factor, as well as the classical mixture toxicity concepts of concentration addition and independent action is explored. Finally, specific attention is given to the exposure-based waiving of environmental risk assessments, as currently implemented in screening or pre-screening phases (tier 0 in Europe, categorical exclusion in the USA), since even low, individually non-toxic concentrations might combine to produce substantial mixture effects.

Keywords: concentration addition; environmental risk assessment; independent action; mixture assessment factor; mixture risk assessment.