How data on transformation products can support the redesign of sulfonamides towards better biodegradability in the environment.

ABSTRACT

Sulfonamide antibiotics (SUAs) released into the environment can affect environmental und human health, e.g., by accelerating the development and selection of antimicrobial resistant bacteria. Benign by Design (BbD) of SUAs is an effective risk prevention approach. BbD principles aim for fast and complete mineralization or at least deactivation of the SUA after release into the aquatic environment. Main objective was to test if mixtures of transformation products (TPs) generated via photolysis of SUAs can be used as an efficient way to screen for similarly effective but better biodegradable SUA alternatives. Six SUAs were photolyzed (Hg ultraviolet (UV) light), and generated UV-mixtures analysed by high performance liquid chromatography coupled to an UV and tandem mass spectrometry detector. UV-mixtures were screened for antibiotic activity (luminescence bacteria test, LBT, on luminescence and growth inhibition of Aliivibrio Fischeri) and environmental biodegradability (manometric respirometry test, MRT, OECD 301F) using untreated parent SUAs in comparison. Additionally, ready environmental biodegradability of three commercially available hydroxylated sulfanilamide derivatives was investigated. SUA-TPs contributed to acute and chronic bacterial luminescence inhibition by UV-mixtures. LBT's third endpoint, growth inhibition, was not significant for UV-mixtures. However, it cannot be excluded for tested TPs as concentrations were lower than parents' concentrations and inhibition by most parental concentrations tested was also not significant. HPLC analysis of MRT samples revealed that one third of SUA-TPs was reduced during incubation. Three of these TPs, likely OH-SIX, OH-SMX and OH-STZ, were of interest for BbD because the sulfonamide moiety is still present. However, hydroxylated sulfanilamide derivatives, tested to investigate the effect of hydroxylation on biodegradability, were not readily biodegraded. Thus, improving mineralization through hydroxylation as a general rule couldn't be confirmed, and no BbD candidate could be identified. This study fills data gaps on bioactivity and environmental biodegradability of SUAs' TP-mixtures. Findings may support new redesign approaches.