Transformation of macrolide antibiotics during chlorination process: Kinetics, degradation products, and comprehensive toxicity evaluation

Antibiotics are ubiquitous in wastewater and surface water and their presence is of grave concern. Chlorination, an important disinfection process used in wastewater treatment plants and waterworks, causes antibiotics to be degraded. However, interactions of antibiotics with chlorine result in the generation of multiple transformation products (TPs). TPs may be more toxic than the parent compounds, but their structures, yields and ecotoxicity remain to be ascertained in most cases. This study examined the degradation by chlorine of two typical macrolide (MLs) antibiotics, erythromycin (ERY) and roxithromycin (ROX), and identified the TPs formed as a result of ERY and ROX chlorination. The ecotoxicity of ERY, ROX and their TPs was evaluated using a combination of bioassay and ECOSAR prediction. The degradation of ERY and ROX followed pseudo-first-order kinetic at the molar ratio of FAC to MLs of 10:1, and the degradation kinetic rate depends on pH values. Six TPs of ERY including three chlorinated TPs, and six TPs of ROX including two chlorinated TPs were identified. The tertiary N of the desosamine moiety of ERY and ROX was determined to be the main reactive site. Demethylation and chlorine substitution at the reactive site are the main degradation pathways of ERY and ROX. ECOSAR results showed that the chlorinated byproducts of ERY TP578, TP542 and TP528, and the reduced hydroxylation products of ROX TP851 exhibited higher ecotoxicity than their parent compounds. However, algae growth inhibition assays indicated that the overall ecotoxicity of the chlorinated ERY or ROX mixture was lower than that of ERY or ROX prior to chlorination. This may be attributed to the removal of the parent compound and lower yields of toxic substances. While the yields of the toxic TPs may be low, their accumulation and combined effects of the TPs and other co-occurring pollutants should be examined further.