Estimating Risks of Pharmaceutical NSAID Mixtures in Surface Waters through Risk Cups : – Implications for Sustainability

Sammanfattning: Background: Use of pharmaceuticals can lead to unchanged or metabolite residues in surface water that may result in negative environmental effects. Sweden has adopted the Generational goal defining direction and changes needed to become a sustainable nation, these align with the UN Sustainable Development Goals (SDGs). Sweden collects and analyzes samples for pharmaceuticals and other contaminants in surface water. Aim: To estimate risks connected to pharmaceuticals in complex mixtures, exemplified by nonsteroidal anti-inflammatory drugs (NSAIDs), and discuss how this can be used to influence the actions needed to reach the Generational goal and the SDGs of Agenda 2030. Methods: Here, measured environmental concentrations (MECs) of the NSAIDs diclofenac, ibuprofen, ketoprofen, and naproxen in Swedish surface waters and in Uppsala’s Fyris River were accessed from a database and used in conjunction with predicted no-effect concentrations (PNECs) from the literature to derive risk quotients(RQ=MEC/PNEC). For all drugs a standardized PNEC derived from OECD guideline base-set tests were found, and for diclofenac and ibuprofen also non-traditional guideline PNECs were identified. Risk cups applied by summation of MEC/PNEC-risk quotients are considered safe if the sum of RQ <1, and as proposed inSOU 2019:45, if one chemical adds more risk than 0.1 to the risk cup it would be better to substitute it for another, if possible. Results and Discussion: Standardized PNECs derived from OECD guideline base-set tests were more than 60-fold greater than non-traditional PNECs for diclofenac and ibuprofen, affecting their individual RQ contribution and total sum of RQ. Based on the non-traditional PNECs, the sum of RQ were more than or near 1 in some cases in Fyris River and elsewhere, thus indicating risk to biota especially in 2010. Diclofenac and ibuprofen typically contributed more to Risk cups than did ketoprofen and naproxen. Especially diclofenac should be considered for substitution, if possible. Swedish sales data indicate at least one more NSAID compound suitable for analysis. In addition, more than 70 pharmaceuticals were identified in Fyris River, adding to pressure on environment from NSAIDs. Risk cups are conservative and require sparse data relative to other methods, and thus can be used to prioritize further efforts. A difficulty is to find relevant ecotoxicological data for pharmaceuticals and therefore an open access database would be of value, preferably complemented with sales data for APIs. However, since a default RQ-value of 0.1 was suggested in SOU 2019:45, a lack of data would not hinder action. Use of risk cups makes it possible to work toward e.g., sustainable production practices benefiting SDG 12. Inaction after identifying a problem conflicts with SDGs 6 and 12, since it would lead to less clean water and more sanitation issues and non-sustainable consumption and production. Conclusion: Risk cups as applied here are suitable as a first tier of pharmaceutical mixture risk estimation since they are quick to perform and demand less data than other methods. Because of their dependence on PNECs, it is important to use a relevant effect test, with results preferably published in an open access database. Diclofenac’s non-traditional risk quotient indicate that the ecological status of the Fyris River is at risk, supporting the official moderate ecological status classification. This thesis suggests an additional NSAID, etoricoxib, as a possible candidate for future studies, based on the number of other NSAIDs on the market and sales numbers, pointing at the usefulness of sales data for a better understanding of risk. In addition to the NSAID group, other pharmaceuticals, active metabolites, and non-pharmaceutical chemicals add to the pressure on the environment. Data on the risk cups and risk quotients can be used as a basis for improvements at sewage treatment plants and factories as well as for launching informative campaigns to physicians and the general public, actions which all may lead to a more sustainable future.