Aquatic photo-transformation and enhanced photoinduced toxicity of ionizable tetracycline antibiotics

Abstract

● Mechanisms for multiple photochemical transformation of tetracyclines were reported.

● The degradation kinetics were dependent on pH and reactivities of dissociated forms.

● Anionic forms reacted faster in the apparent photolysis and photooxidation processes.

● Different pathways and various intermediates occurred for the three reactions.

● The major by-products showed similar or more toxicities than the parent antibiotics.

Most antibiotics contain ionizable groups that undergo acid-base dissociation giving rise to diverse dissociated forms in aquatic systems depending on the pH of the system. In sunlit surface waters, photochemical transformation plays a crucial role in determining the fate of antibiotics. This study presents a comprehensive examination of the photo-transformation degradation kinetics, pathways and photoinduced toxicity of three widely detected tetracyclines (TCs): tetracycline (TC), oxytetracycline (OTC), and chlortetracycline (CTC). Under simulated sunlight (λ > 290 nm), their apparent photolysis followed pseudo-first-order kinetics, with rate constants significantly increasing from H₂TCs⁰ to TCs^2–. Through competition kinetic experiments and matrix calculations, it was found that the anions HTCs^– or TCs^2– (pH ~ 8–10) were more reactive toward hydroxyl radicals (•OH), while TCs^2– (pH ~ 10) reacted the fastest with singlet oxygen (¹O₂). Considering the dissociated species, the total environmental photo-transformation half-lives of TCs were determined, revealing a strong dependence on the water pH and seasonal variation in sunlight. Generally, apparent photolysis was the dominant photochemical process, followed by ¹O₂ and •OH oxidation. Different transformation pathways for the three reactions were determined based on the key photoproducts identified using HPLC-MS/MS. Toxicity tests and ECOSAR software calculations confirmed that the intermediates produced by the •OH and ¹O₂ photo-oxidation processes were more toxic than the parent compounds. These findings significantly enhance our understanding of the complex photochemical fate and associated risks of TCs in aqueous environments.

Graphical abstract

Keywords

Tetracyclines / Dissociation / Photodegradation kinetics / Reactive oxygen species / Transformation products / Risks

References

[1] Adamek E, Baran W, Sobczak A. (2016). Assessment of the biodegradability of selected sulfa drugs in two polluted rivers in Poland: effects of seasonal variations, accidental contamination, turbidity and salinity. Journal of Hazardous Materials, 313: 147–158

[2] Al Housari F, Vione D, Chiron S, Barbati S. (2010). Reactive photoinduced species in estuarine waters: characterization of hydroxyl radical, singlet oxygen and dissolved organic matter triplet state in natural oxidation processes. Photochemical & Photobiological Sciences, 9(1): 78–86

[3] An J, Chen H, Wei S, Gu J. (2015). Antibiotic contamination in animal manure, soil, and sewage sludge in Shenyang, northeast China. Environmental Earth Sciences, 74(6): 5077–5086

[4] Anjali R, Shanthakumar S. (2019). Insights on the current status of occurrence and removal of antibiotics in wastewater by advanced oxidation processes. Journal of Environmental Management, 246: 51–62

[5] Bodrato M, Vione D. (2014). APEX (Aqueous photochemistry of environmentally occurring xenobiotics): a free software tool to predict the kinetics of photochemical processes in surface waters. Environmental Science. Processes & Impacts, 16(4): 732–740

[6] Boreen A L, Arnold W A, Mcneill K. (2004). Photochemical fate of sulfa drugs in the aquatic environment: sulfa drugs containing five-membered heterocyclic groups. Environmental Science & Technology, 38(14): 3933–3940

[7] Boreen A L, Arnold W A, Mcneill K. (2005). Triplet-sensitized photodegradation of sulfa drugs containing six-membered heterocyclic groups: identification of an SO₂ extrusion photoproduct. Environmental Science & Technology, 39(10): 3630–3638

[8] Chen W, Huang C. (2011). Transformation kinetics and pathways of tetracycline antibiotics with manganese oxide. Environmental Pollution, 159(5): 1092–1100

[9] Chen Y, Li H, Wang Z, Tao T, Hu C. (2011). Photoproducts of tetracycline and oxytetracycline involving self-sensitized oxidation in aqueous solutions: effects of Ca²⁺ and Mg²⁺. Journal of Environmental Sciences, 23(10): 1634–1639

[10] Cheng J, Jiang L, Sun T, Tang Y, Du Z, Lee L, Zhao Q. (2019). Occurrence, seasonal variation and risk assessment of antibiotics in the surface water of north China. Archives of Environmental Contamination and Toxicology, 77(1): 88–97

[11] Edhlund B L, Arnold W A, Mcneill K. (2006). Aquatic photochemistry of nitrofuran antibiotics. Environmental Science & Technology, 40(17): 5422–5427

[12] Felis E, Buta-Hubeny M, Zieliński W, Hubeny J, Harnisz M, Bajkacz S, Korzeniewska E. (2022). Solar-light driven photodegradation of antimicrobials, their transformation by-products and antibiotic resistance determinants in treated wastewater. Science of the Total Environment, 836: 155447

[13] Ge L, Chen J, Wei X, Zhang S, Qiao X, Cai X, Xie Q. (2010). Aquatic photochemistry of fluoroquinolone antibiotics: kinetics, pathways, and multivariate effects of main water constituents. Environmental Science & Technology, 44(7): 2400–2405

[14] Ge L, Halsall C, Chen C, Zhang P, Dong Q, Yao Z. (2018). Exploring the aquatic photodegradation of two ionisable fluoroquinolone antibiotics-gatifloxacin and balofloxacin: degradation kinetics, photobyproducts and risk to the aquatic environment. Science of the Total Environment, 633: 1192–1197

[15] GeLNaG ZhangSLi KZhangPRenHYaoZ (2015). New insights into the aquatic photochemistry of fluoroquinolone antibiotics: direct photodegradation, hydroxyl-radical oxidation, and antibacterial activity changes. Science of the Total Environment, 527-528: 12-17

[16] Ge L, Zhang P, Halsall C, Li Y, Chen C, Li J, Sun H, Yao Z. (2019). The importance of reactive oxygen species on the aqueous phototransformation of sulfonamide antibiotics: kinetics, pathways, and comparisons with direct photolysis. Water Research, 149: 243–250

[17] Guo H, Chen Z, Lu C, Guo J, Li H, Song Y, Han Y, Hou Y. (2020). Effect and ameliorative mechanisms of polyoxometalates on the denitrification under sulfonamide antibiotics stress. Bioresource Technology, 305: 123073

[18] Han C H, Park H D, Kim S B, Yargeau V, Choi J W, Lee S H, Park J A. (2020). Oxidation of tetracycline and oxytetracycline for the photo-Fenton process: their transformation products and toxicity assessment. Water Research, 172: 115514

[19] HeYYuanQ MathieuJStadler LSenehiNSunRAlvarezP J (2020). Antibiotic resistance genes from livestock waste: occurrence, dissemination, and treatment. npj Clean Water, 3(1): 4

[20] Hu S, Zhang H, Yang Y, Cui K, Ao J, Tong X, Shi M, Wang Y, Chen X, Li C. . (2024). Comprehensive insight into the occurrence characteristics, influencing factors and risk assessments of antibiotics in the Chaohu Basin. Frontiers of Environmental Science & Engineering, 18(5): 57–71

[21] Jiao S, Zheng S, Yin D, Wang L, Chen L. (2008a). Aqueous oxytetracycline degradation and the toxicity change of degradation compounds in photoirradiation process. Journal of Environmental Sciences, 20(7): 806–813

[22] Jiao S, Zheng S, Yin D, Wang L, Chen L. (2008b). Aqueous photolysis of tetracycline and toxicity of photolytic products to luminescent bacteria. Chemosphere, 73(3): 377–382

[23] Jin X, Xu H, Qiu S, Jia M, Wang F, Zhang A, Jiang X. (2017). Direct photolysis of oxytetracycline: Influence of initial concentration, pH and temperature. Journal of Photochemistry and Photobiology A Chemistry, 332: 224–231

[24] Knapp C, Cardoza L, Hawes J, Wellington E, Larive C, Graham D. (2005). Fate and effects of enrofloxacin in aquatic systems under different light conditions. Environmental Science & Technology, 39(23): 9140–9146

[25] Latch D E, Packer J L, Stender B L, Vanoverbeke J, Arnold W A, Mcneill K. (2005). Aqueous photochemistry of triclosan: formation of 2,4-dichlorophenol, 2,8-dichlorodibenzo-p-dioxin, and oligomerization products. Environmental Toxicology and Chemistry, 24(3): 517–525

[26] Li R, Zhao C, Yao B, Li D, Yan S, O’Shea K E, Song W. (2016). Photochemical transformation of aminoglycoside antibiotics in simulated natural waters. Environmental Science & Technology, 50(6): 2921–2930

[27] Li S, Shi W, Liu W, Li H, Zhang W, Hu J, Ke Y, Sun W, Ni J. (2018). A duodecennial national synthesis of antibiotics in China’s major rivers and seas (2005–2016). Science of the Total Environment, 615: 906–917

[28] Li T, Ouyang W, Lin C, Wang J, Cui X, Li Y, Guo Z, Zhu W, He M. (2023). Occurrence, distribution, and potential ecological risks of antibiotics in a seasonal freeze-thaw basin. Journal of Hazardous Materials, 459: 132301

[29] Liu H, Niu C, Huang D, Liang C, Guo H, Yang Y, Li L. (2023). Unravelling the role of reactive oxygen species in ultrathin Z-scheme heterojunction with surface zinc vacancies for photocatalytic H₂O₂ generation and CTC degradation. Chemical Engineering Journal, 465: 143007

[30] Liu X, Lu S, Guo W, Xi B, Wang W. (2018). Antibiotics in the aquatic environments: a review of lakes, China. Science of the Total Environment, 627: 1195–1208

[31] Liu Y, Mekic M, Carena L, Vione D, Gligorovski S, Zhang G, Jin B. (2020). Tracking photodegradation products and bond-cleavage reaction pathways of triclosan using ultra-high resolution mass spectrometry and stable carbon isotope analysis. Environmental Pollution, 264: 114673

[32] Mill T. (1999). Predicting photoreaction rates in surface waters. Chemosphere, 38(6): 1379–1390

[33] Niu J, Li Y, Wang W. (2013). Light-source-dependent role of nitrate and humic acid in tetracycline photolysis: kinetics and mechanism. Chemosphere, 92(11): 1423–1429

[34] Oka H, Ikai Y, Kawamura N, Yamada M, Harada K, Ito S, Suzuki M. (1989). Photodecomposition products of tetracycline in aqueous solution. Journal of Agricultural and Food Chemistry, 37(1): 226–231

[35] Park J A, Pineda M, Peyot M L, Yargeau V. (2023). Degradation of oxytetracycline and doxycycline by ozonation: degradation pathways and toxicity assessment. Science of the Total Environment, 856: 159076

[36] Ping Q, Yan T, Wang L, Li Y, Lin Y. (2022). Insight into using a novel ultraviolet/peracetic acid combination disinfection process to simultaneously remove antibiotics and antibiotic resistance genes in wastewater: mechanism and comparison with conventional processes. Water Research, 210: 118019

[37] Qi N, Wang P, Wang C, Ao Y. (2018). Effect of a typical antibiotic (tetracycline) on the aggregation of TiO₂ nanoparticles in an aquatic environment. Journal of Hazardous Materials, 341: 187–197

[38] Riu A, Le Maire A, Grimaldi M, Audebert M, Hillenweck A, Bourguet W, Balaguer P, Zalko D. (2011). Characterization of novel ligands of ERα, Erβ, and PPARγ: the case of halogenated bisphenol A and their conjugated metabolites. Toxicological Sciences, 122(2): 372–382

[39] Sciscenko I, Arques A, Varga Z, Bouchonnet S, Monfort O, Brigante M, Mailhot G. (2021). Significant role of iron on the fate and photodegradation of enrofloxacin. Chemosphere, 270: 129791

[40] Song C, Liu H, Guo S, Wang S. (2020). Photolysis mechanisms of tetracycline under UV irradiation in simulated aquatic environment surrounding limestone. Chemosphere, 244: 125582

[41] Su Z, Wang K, Yang F, Zhuang T. (2023). Antibiotic pollution of the Yellow River in China and its relationship with dissolved organic matter: distribution and source identification. Water Research, 235: 119867

[42] Tian Y, Ying C, Zhang L, Huang H, Song S, Mei R, Li J. (2024). Unveiling the inhibition of chlortetracycline photodegradation and the increase of toxicity when coexisting with silver nanoparticles. Science of the Total Environment, 912: 168443

[43] Tran N H, Hoang L, Nghiem L D, Nguyen N M H, Ngo H H, Guo W, Trinh Q T, Mai N H, Chen H, Nguyen D D. . (2019). Occurrence and risk assessment of multiple classes of antibiotics in urban canals and lakes in Hanoi, Vietnam. Science of the Total Environment, 692: 157–174

[44] Vione D, Minella M, Maurino V, Minero C. (2014). Indirect photochemistry in sunlit surface waters: photoinduced production of reactive transient species. Chemistry, 20(34): 10590–10606

[45] Wang Q, He X, Xiong H, Chen Y, Huang L. (2022). Structure, mechanism, and toxicity in antibiotics metal complexation: recent advances and perspectives. Science of the Total Environment, 848: 157778

[46] Werner J J, Arnold W A, Mcneill K. (2006). Water hardness as a photochemical parameter: tetracycline photolysis as a function of calcium concentration, magnesium concentration, and pH. Environmental Science & Technology, 40(23): 7236–7241

[47] Xu H, Cooper W J, Jung J, Song W. (2011). Photosensitized degradation of amoxicillin in natural organic matter isolate solutions. Water Research, 45(2): 632–638

[48] Xu L, Zhang H, Xiong P, Zhu Q, Liao C, Jiang G. (2021a). Occurrence, fate, and risk assessment of typical tetracycline antibiotics in the aquatic environment: a review. Science of the Total Environment, 753: 141975

[49] Xu T, Fang Y, Tong T, Xia Y, Liu X, Zhang L. (2021b). Environmental photochemistry in hematite-oxalate system: Fe (III)-Oxalate complex photolysis and ROS generation. Applied Catalysis B: Environmental, 283: 119645

[50] Ye C, Chen Y, Feng L, Wan K, Li J, Feng M, Yu X. (2022). Effect of the ultraviolet/chlorine process on microbial community structure, typical pathogens, and antibiotic resistance genes in reclaimed water. Frontiers of Environmental Science & Engineering, 16(8): 100–113

[51] Yu J, Chen X, Zhang Y, Cui X, Zhang Z, Guo W, Wang D, Huang S, Chen Y, Hu Y. . (2022). Antibiotic azithromycin inhibits brown/beige fat functionality and promotes obesity in human and rodents. Theranostics, 12(3): 1187–1203

[52] Yuan X, Cui K, Chen Y, Wu S, Zhang Y, Liu T. (2023). Response of antibiotic and heavy metal resistance genes to the co-occurrence of gadolinium and sulfamethoxazole in activated sludge systems. Frontiers of Environmental Science & Engineering, 17(12): 154–164

[53] Zhang C, Chen Y, Chen S, Guan X, Zhong Y, Yang Q. (2023). Occurrence, risk assessment, and in vitro and in vivo toxicity of antibiotics in surface water in China. Ecotoxicology and Environmental Safety, 255: 114817

[54] Zhang M, He L, Liu Y, Zhao J, Liu W, Zhang J, Chen J, He L, Zhang Q, Ying G. (2019). Fate of veterinary antibiotics during animal manure composting. Science of the Total Environment, 650: 1363–1370

[55] Zhang T, Cheng F, Yang H, Zhu B, Li C, Zhang Y N, Qu J, Peijnenburg W J. (2022a). Photochemical degradation pathways of cell-free antibiotic resistance genes in water under simulated sunlight irradiation: experimental and quantum chemical studies. Chemosphere, 302: 134879

[56] Zhang X, Kamali M, Yu X, Costa M E V, Appels L, Cabooter D, Dewil R. (2022b). Kinetics and mechanisms of the carbamazepine degradation in aqueous media using novel iodate-assisted photochemical and photocatalytic systems. Science of the Total Environment, 825: 153871

[57] Zhang X, Su H, Gao P, Li B, Feng L, Liu Y, Du Z, Zhang L. (2022c). Effects and mechanisms of aged polystyrene microplastics on the photodegradation of sulfamethoxazole in water under simulated sunlight. Journal of Hazardous Materials, 433: 128813

[58] ZhangYZhang CParkerD BSnowD DZhouZ LiX (2013). Occurrence of antimicrobials and antimicrobial resistance genes in beef cattle storage ponds and swine treatment lagoons. Science of the Total Environment, 463-464: 631-638

[59] Zheng J, Zhang P, Li X, Ge L, Niu J. (2023). Insight into typical photo-assisted AOPs for the degradation of antibiotic micropollutants: mechanisms and research gaps. Chemosphere, 343: 140211

[60] Zhou Y, Cheng F, He D, Zhang Y, Qu J, Yang X, Chen J, Peijnenburg W J. (2021). Effect of UV/chlorine treatment on photophysical and photochemical properties of dissolved organic matter. Water Research, 192: 116857

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