Aquatic ecotoxicity of pharmaceuticals including the assessment of combination effects

Toxicol Lett. 2003 May 15;142(3):185-94. doi: 10.1016/s0378-4274(03)00068-7.


To evaluate the ecotoxicological potential of ten prescription drugs against aquatic organisms from different taxonornical classes, a set of biotests were performed using the cladoceran Daphnia magna, the chlorophyte Desmodesmus subspicatus and the macrophyte Lemna minor. Endpoints were immobilisation for Daphnia and inhibition of the average growth rate for Desmodesmus and Lemna. For most of the substances, toxicities were moderate, with EC(50)s in the range from 10 to 100 mgl(-1) or even far above, whereas Lemna was the most sensitive test species in the majority of all tested compounds. Tests with combinations of various pharmaceuticals revealed stronger effects than expected from the effects measured singly. Clofibrinic acid and Carbamazepine have been found to act by a non-specific mode of action (non-polar narcosis), and with Daphnia the combination effect of these substances followed the concept of concentration addition, while in the algae test the concept of independent action could be used to calculate the mixture toxicity. The anti-inflammatory drugs Diclofenac and Ibuprofen have also been found to act unspecific by non-polar narcosis and to follow the concept of concentration addition in the algal test as well as in the Daphnia test. The measured toxicities of the tested pharmaceuticals shows that acute effect of single substances in the aquatic environment are very unlikely. But we should keep in mind that considerable combination effects can occur and that toxicity data from chronic studies are needed to assess the environmental risk of drug residues.

MeSH terms

  • Animals
  • Araceae / drug effects
  • Araceae / growth & development
  • Chlorophyta / drug effects
  • Chlorophyta / growth & development
  • Daphnia / drug effects
  • Daphnia / physiology
  • Dose-Response Relationship, Drug
  • Drug Combinations*
  • Drug-Related Side Effects and Adverse Reactions*
  • Ecosystem*
  • Environmental Monitoring / methods*
  • Toxicity Tests
  • Water Pollutants, Chemical / adverse effects*


  • Drug Combinations
  • Water Pollutants, Chemical