Comprehensive prioritisation scheme for active pharmaceutical ingredients in Denmark

Abstract

Active pharmaceutical ingredients (APIs) can cause severe adverse effects if released into the environment. In response to the 2574 APIs approved in Denmark and costly environmental monitoring initiatives, a prioritisation scheme is presented to identify candidate substances for further investigation, based on their hazard, use and risk. The proposed prioritisation scheme consists of three subsequent filters; human toxicology and ecotoxicology followed by reported Danish use and lastly measured or predicted environmental concentration and risk ratios based on these. To generate a final list of 300 APIs, actions such as assigning scores for missing data were implemented. These substances may inform future monitoring campaigns focused on pharmaceutical contamination in aquatic environments through effluent discharge. All in all, 84% among the top-50 priority APIs have not previously been included in chemical analysis of any environmental samples in Denmark. These APIs belonged to therapeutic groups such as treatments for hypertension, antibiotics, antifungals, antineoplastics, and medicines affecting the nervous system. Of particular concern is metformin, clindamycin and clotrimazole as these are all amongst the highest ranked based on risk, and also appear on the EU commission's watch list of substances for EU-wide monitoring in the field of water policy. The scheme can be updated, adapted and implemented in other geographical regions.