The influence of pH and dissolved organic carbon on the ecotoxicity of ampicillin and clarithromycin

The impacts of water chemistry properties including pH and dissolved organic carbon (DOC) on the ecotoxicity of active pharmaceutical ingredients (APIs) are increasingly evident. These impacts are a result of alterations in API bioavailability: pH regulates the bioavailability of many ionizable APIs via chemical speciation, whereas DOC interacts with several APIs to inhibit the APIs from traversing the membrane system of organisms. In this study, we examined the influences of pH and DOC on the bioavailability of ampicillin (AMP) and clarithromycin (CLA) with the help of a bioavailability model. The effects on bioavailability were quantified by ecotoxicity observed in cyanobacteria growth inhibition tests with Microcystis aeruginosa PCC7806. The median effect concentration (96 h-EC50total) of AMP increased by 5-fold when pH raised from 7.4 to 9.0, suggesting the zwitterionic AMP+/species being higher in bioavailability than the negatively charged AMP- species. CLA ecotoxicity showed no significant pH-dependency, suggesting CLA+ and CLA0 species to be equally bioavailable, albeit it correlated significantly with M. aeruginosa growth rate in negative controls. In addition, DOC demonstrated no significant effects on the ecotoxicity of AMP or CLA. Overall, together with earlier results on ciprofloxacin, our data show that bioavailability relations with pH and DOC are variable among different antibiotics. Factors other than chemical speciation alone could play a role in their bioavailability, such as their molecular size and polarity.