The single substance and mixture toxicity of quinolones to the bioluminescent bacterium Vibrio fischeri

Quinolones are one of the most important group of synthetic antibiotics use d in aquaculture. We studied the single substance and mixture toxicity of t en quinolones using a long term bioluminescence inhibition assay with the m arine bacterium Vibrio fischeri as the test organism. All tested quinolones are highly toxic to the test organism with EC50 Values ranging from 14 mu g/l for ofloxacin to 1020 mu g/l for pipemidic acid. Adapting the approach outlined in EEC directive 93/21/EEC to these results, all but one of the te n quinolones belong to the group classified as being 'very toxic to aquatic organisms' (EC50 below 1 mg/l). On the basis of the concentration-response relationships of the single compounds, the mixture toxicity of the ten com pounds was estimated by the concepts of concentration addition and independ ent action. Complete concentration-response relationships were experimental ly recorded for the quinolone mixture in three different mixture ratios, ba sed on the relative toxicity of the components (EC50, EC1 and NOEC). The re sults show that the mixture toxicity of the quinolones is best predictable by concentration addition, whereas independent action underestimates the to xicity of the mixture. As the quinolones have an identical specific mechani sm of action (the inhibition of bacterial gyrases), these results are in ag reement with the pharmacological assumptions that form the basis of the con cept of concentration addition. It is therefore concluded, that concentrati on addition can be useful for hazard assessment procedures of mixtures of s imilarly acting compounds. One important implication of this concept is tha t even mixture components that are present only at their individual no obse rved effect concentrations (NOECs) contribute to the overall toxicity of th e mixture. Under these conditions more than 99% effect of the quinolone mix ture are observed. This result emphasises the unsuitability of NOECs as an approximation of a 'safe' concentration. (C) 2000 Elsevier Science B.V. All rights reserved.