Mixture toxicity of the anti-inflammatory drugs diclofenac, ibuprofen, naproxen, and acetylsalicylic acid

• Published in: Ecotoxicology and environmental safety 2004-11, Vol.59 (3), p.309-315
• Main Author: Cleuvers, Michael
• Format: Article
• Language: English
• Subjects: Animal, plant and microbial ecology; Animals; Anti-Inflammatory Agents, Non-Steroidal - pharmacology; Anti-Inflammatory Agents, Non-Steroidal - toxicity; Applied ecology; Biological and medical sciences; Chlorophyta; Concentration addition; Daphnia; Desmodesmus; Drug Interactions; Ecotoxicology, biological effects of pollution; Freshwater; Fundamental and applied biological sciences. Psychology; General aspects; Lethal Dose 50; Mixture toxicity; Narcosis; Pharmaceuticals; QSAR; Quantitative Structure-Activity Relationship; Risk Assessment; Water Pollutants, Chemical - pharmacology; Water Pollutants, Chemical - toxicity
• ISSN: 0147-6513; 1090-2414
• DOI: 10.1016/S0147-6513(03)00141-6

The ecotoxicity of the nonsteroidal anti-inflammatory drugs (NSAIDs) diclofenac, ibuprofen, naproxen, and acetylsalicylic acid (ASA) has been evaluated using acute Daphnia and algal tests. Toxicities were relatively low, with half-maximal effective concentration (EC50) values obtained using Daphnia in the range from 68 to 166mgL−1 and from 72 to 626mgL−1 in the algal test. Acute effects of these substances seem to be quite improbable. The quantitative structure–activity relationships (QSAR) approach showed that all substances act by nonpolar narcosis; thus, the higher the n-octanol/water partitioning coefficient (logKow) of the substances, the higher is their toxicity. Mixture toxicity of the compounds could be accurately predicted using the concept of concentration addition. Toxicity of the mixture was considerable, even at concentrations at which the single substances showed no or only very slight effects, with some deviations in the Daphnia test, which could be explained by incompatibility of the very steep dose–response curves and the probit analysis of the data. Because pharmaceuticals in the aquatic environment occur usually as mixtures, an accurate prediction of the mixture toxicity is indispensable for environmental risk assessment.