Development of a conceptual model to account for pH-dependent toxicity of basic pharmaceuticals in the green algae Scenedesmus vacuolatus

Our previous studies as well as analysis of literature data revealed that pharmaceuticals with aliphatic amine function exert an extraordinary high toxicity in algae, which is similar to that exhibited by specifically acting herbicides. However, the clear identification of the underlying mode of action is still pending because the time and endpoint pattern pointed to baseline toxicity despite the high toxic ratio (ratio between predicted baseline toxicity EC50 and experimental EC50), which serves as a measure for specificity of effect. On this basis we hypothesize that the high toxicity of amines in algae is not due to a highly specific mode of toxic action but due to speciation effects of the amine function. The pH-dependent toxicity of 5 basic pharmaceuticals can be explained by an ion-trapping mechanism. We hypothesize that only the neutral species can permeate the membrane. Since algae are capable of biological homeostasis, the fraction of charged species can be different in the cytoplasm and in the external medium depending on the pH in the cytoplasm and the acidity of the base. If the high toxicity of basic pharmaceuticals in algae is a speciation effect, then the internal effect concentrations in the cytoplasm and at the target membranes should be similar with varying external pH values. The developed model shows that the specific toxicity of basic pharmaceuticals with amine function in algae is a toxicokinetic effect, not a toxicodynamic effect related to a specific mode of toxic action. This toxicokinetic effect is presumably more pronounced for algae than for other aquatic organisms (for which these aliphatic amines are generally baseline toxicants) because green algae have a relatively high internal pH