Application of the combination index (CI)-isobologram equation to study the toxicological interactions of lipid regulators in two aquatic bioluminescent organisms

Abstract

Pharmaceuticals in the aquatic environment do not appear singly and usually occur as complex mixtures, whose combined effect may exhibit toxicity to the aquatic biota. We report an environmental application of the combination index (CI)-isobologram equation, a method widely used in pharmacology to study drug interactions, to determine the nature of toxicological interactions of three fibrates toward two aquatic bioluminescent organisms, Vibrio fischeri and the self-luminescent cyanobacterial recombinant strain Anabaena CPB4337. The combination index-isobologram equation method allows computerized quantitation of synergism, additive effect and antagonism. In the Vibrio test, the fibrate combinations showed antagonism at low effect levels that turned into an additive effect or synergism at higher effect levels; by contrast, in the Anabaena test, the fibrate combinations showed a strong synergism at the lowest effect levels and a very strong antagonism at high effect levels. We also evaluated the nature of the interactions of the three fibrates with a real wastewater sample in the cyanobacterial test. We propose that the combination index-isobologram equation method can serve as a useful tool in ecotoxicological assessment.