Predictive environmental risk assessment of chemical mixtures: a conceptual framework

Environmental risks of chemicals are still often assessed substance-by-substance, neglecting mixture effects. This may result in risk underestimations, as the typical exposure is toward multicomponent chemical "cocktails". We use the two well established mixture toxicity concepts (Concentration Addition (CA) and Independent Action (IA)) for providing a tiered outline for environmental hazard and risk assessments of mixtures, focusing on general industrial chemicals and assuming that the "base set" of data (EC50s for algae, crustaceans, fish) is available. As mixture toxicities higher than predicted by CA are rare findings, we suggest applying CA as a precautious first tier, irrespective of the modes/mechanisms of action of the mixture components. In particular, we prove that summing up PEC/PNEC ratios might serve as a justifiable CA-approximation, in order to estimate in a first tier assessment whether there is a potential risk for an exposed ecosystem if only base-set data are available. This makes optimum use of existing single substance assessments as more demanding mixture investigations are requested only if there are first indications of an environmental risk. Finally we suggest to call for mode-of-action driven analyses only if error estimations indicate the possibility for substantial differences between CA- and IA-based assessments.