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Photolysis is currently being discussed and investigated as additional stage or at least part of an extended treatment for sustainable water purification in waste water treatment plants. This study describes the photoinduced degradation of four macrolide antibiotics using UVC/VUV-irradiation. Special attention was paid to the determination of ecotoxicity of the formed photoinduced degradation products. To this purpose, MIC values were determined and QSAR analysis was performed. Photo-induced degradation rates of the drug substances ranged from 0.39 min–1 to 2.47 min–1, with azithromycin showing the slowest degradation, followed by erythromycin and spiramycin. The degradation of tylosin proceeded the fastest. QSAR analysis indicated that most of the identified photoproducts were less eco-toxic than the original drugs. The corresponding MIC analysis demonstrated that the four macrolides were ineffective against the gram-negative Pseudomonas fluorescens but effective against the gram-positive Bacillus subtilis. The MIC determination of irradiated tylosin solutions showed exemplarily that prolongation of the irradiation times led to increasing MIC values of the solution, reduced efficacy and hence potentially less eco-toxicity of the irradiated solution and the degradates therein. [ABSTRACT FROM AUTHOR]