In silico toxicity evaluation for transformation products of antimicrobials, from aqueous photolysis degradation

• Published in: The Science of the total environment Vol. 828; p. 154109
• Main Authors: Segalin, Jeferson, Arsand, Juliana Bazzan, Jank, Louise, Schwalm, Cristiane Storck, Streit, Livia, Pizzolato, Tânia Mara
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.07.2022
• Subjects: Anti-Infective Agents - toxicity; Antimicrobials; Ciprofloxacin - toxicity; Mutagens - chemistry; Norfloxacin - toxicity; Photolysis; QSAR predictive models; Sulfamethoxazole; Transformation products; Water; Water Pollutants, Chemical - analysis; Transformation products; QSAR predictive models; Photolysis; Antimicrobials
• ISSN: 0048-9697; 1879-1026
• DOI: 10.1016/j.scitotenv.2022.154109

This study investigates degradation processes of three antimicrobials in water (norfloxacin, ciprofloxacin, and sulfamethoxazole) by photolysis, focusing on the prediction of toxicity endpoints via in silico quantitative structure-activity relationship (QSAR) of their transformation products (TPs). Photolysis experiments were conducted in distilled water with individual solutions at 10 mg L−1 for each compound. Identification of TPs was performed by means of LC-TOF-MS, employing a method based on retention time, exact mass fragmentation pattern, and peak intensity. Ten main compounds were identified for sulfamethoxazole, fifteen for ciprofloxacin, and fifteen for norfloxacin. Out of 40 identified TPs, 6 have not been reported in the literature. Based on new data found in this work, and TPs already reported in the literature, we have proposed degradation pathways for all three antimicrobials, providing reasoning for the identified TPs. QSAR risk assessment was carried out for 74 structures of possible isomers. QSAR predictions showed that all 19 possible structures of sulfamethoxazole TPs are non-mutagenic, whereas 16 are toxicant, 18 carcinogenic, and 14 non-readily biodegradable. For ciprofloxacin, 28 out of the 30 possible structures for the TPs are mutagenic and non-readily biodegradable, and all structures are toxicant and carcinogenic. All 25 possible norfloxacin TPs were predicted mutagenic, toxicant, carcinogenic, and non-readily biodegradable. Results obtained from in silico QSAR models evince the need of performing risk assessment for TPs as well as for the parent antimicrobial. An expert analysis of QSAR predictions using different models and degradation pathways is imperative, for a large variety of structures was found for the TPs. [Display omitted] •Workflow to identify TPs, by high resolution mass spectrometry•Compilation of the main transformation products of the three antimicrobials•Degradation photolysis pathways for SMX, CFX and NFX, including six new TPs•Proposition of chemical structures for new TPs (3 for SMX, 2 for CFX, and 1 for NFX)•VEGA QSAR risk assessment for 74 TPs of SMX, CFX and NFX