PBT/PMT assessment of active pharmaceutical ingredients.

Abstract

The EU Commission proposal for a new EU pharmaceutical legislation considers PBT (persistence-bioaccumulation-toxicity) and PMT (persistence-mobility-toxicity) criteria for pharmaceuticals. Under current environmental risk assessment guidance, a PBT assessment is required regardless of the predicted environmental concentrations. However, consumption volumes of pharmaceuticals are contingent on marketing approval by EMA and are therefore predictable and their toxicological potency is established prior to any regulatory approval. Consumption volume and toxicological potency of pharmaceuticals span many orders of magnitude and are strong risk determinants. Routine data generation to evaluate persistence, mobility and bioaccumulation hazards as a means of pinpointing pharmaceuticals of increased environmental concern is therefore of questionable added value. We present options to derive action triggers for PBT and/or PMT screening using exposure predictions and toxicological potency data. Our simulations demonstrate that an exposure-based action limit can be established as a trigger for PMT assessment, while a combined trigger based on exposure levels and mammalian toxicity is proposed for PBT assessment. The proposed approach is conservatively designed to ensure that compounds with any potential risks a) of secondary poisoning (main concern for PBT substances) and b) to groundwater/drinking water (main concern for PMT substances) are targeted for full evaluation.