Toxicity of Pharmaceuticals

  • Madhu Sharma CSKHPKV, Palampur H.P.


Manufacturing and release of pharmaceuticals are increasing in different countries of the world especially in developing countries. The discharge from wastewater plant containing a wide range of classes of pharmaceuticals. Rapidly growing economy, aquaculture and livestock industry has led to increased incidences of diseases and has increased the release of pharmaceuticals into natural environment which is affecting the biodiversity of hotspots adversely. This review mainly focuses on antibiotic oxytetracyclin, its use, structure, occurrence in aquatic environments and other environmental compartments, lastly an overview of toxicity to fish is provided. The threat posed by these pharmaceuticals are evident from the studies showing their toxic effect on different aquatic organisms.


Keywords: Pharmaceuticals, Oxytetracyclin, toxicity


1. Shao ZJ. Aquaculture pharmaceuticals and biologicals: Current perspectives and future possibilities. Advanced Drug Delivery Reviews 2001; 50(3): 229-43 10.1016/S0169-409X(01)00159-4
2. Wise R. Antimicrobial resistance: priorities for action. J. Antimicrob Chemoth 2002; 49, 585–586.
3. Kümmerer K. Antibiotics in the aquatic environment – A review – Part I Chemosphere 2009; 75: 417–434.
4. Grave K, Torren-Edo J, Mackay D. Comparison of the sales of veterinary antibacterial agents between 10 European countries. J Antimicrobial Chemotherapy 2010;65:2037–2040.
5. Klein EY, Thomas P, Boeckel V, Elena M, Martinez Pant S, Gandra S, Simon A, Levin H, Laxminarayan R. Global increase and geographic convergence in antibiotic consumption between 2000 and 2015. Proceedings of the National Academy of Sciences 115(15):201717295
6. Kim KR, Owens G, Kwon SI, So KH, Lee DB, Ok YS. Occurrence and environmental fate of veterinary antibiotic in the terrestrial environment. Water Air Soil Pollut 2011; 163:163–174

7. Singer AC, Shaw, H. Rhodes V, Hart, A. (2016). Review of Antimicrobial Resistance in the Environment and Its Relevance to Environmental Regulators. Front. Microbiol.
8. Kallummal M, Bugalya K.2012. Trends in India's Trade in Pharmaceutical Sector: SomeInsights. 1-97
9. Fick J, Hanna SO¨ Derstro¨ M, Richard H. Lindberg, Phan C. Tysklind M, LARSSON DG. Contamination of surface, ground, and drinking water from pharmaceutical production. Environ Toxicol Chem 2009; 28(12): 2522–2527.
10. Burkina V, Zlabek V, Zamaratskaia, G. Effects of pharmaceuticals present in aquatic environment on Phase I metabolism in fish. Environ Toxicol Pharmaco2015; 40 (2):430-444.
11. Chopra I, Roberts MC. Tetracycline antibiotics: mode of action, applications, molecular biology and epidemiology of bacterial resistance. Microbiol Mol Biol Rev 2001; 65: 232–260.
12. McNamara TF, Golub LM, D'Angelo G, Ramamurthy, NS. The synthesis and characterization of non-antimicrobial chemically-modified tetracycline (CMT) (Abstract). J Dent Res 1986; 65: 515, 1986.
13. Golub LM, Ramamurthy NS, McNamara TF, Greenwald RA, Rifkin BR. Tetracyclines inhibit connective tissue breakdown: new therapeutic implications for an old family of drugs. Crit Rev Oral Biol Med 1991; 2: 297–321.
14. Wu Y, Yue Q, Gao Y, Ren Z, Gao B. Performance of bimetallic nanoscale zero-valent iron particles for removal of oxytetracycline. J Environ Sci 2017; 69:173-182.
15. Zounkova R, Klimesova Z, Nepejchalova L, Blaha L. Complex evaluation of ecotoxicity and genotoxicity of antimicrobials oxytetracycline and flumequine used in aquaculture. Environ Toxicol Chemi 2011; 30(5):1184-9.
16. Shi Z.-J, Hu HY, Shen YY, Xu JJ, Shi ML, Jin CR. Long-term effects of oxytetracycline (OTC) on the granule-based anammox: Process performance and occurrence of antibiotic resistance genes. Biochemical Engineering J 2017; 127: p. 110-118.
17. Wang C, Pan X, Fan Y, Chen Y, Mu W. The oxidative stress response of oxytetracycline in the ciliate Pseudocohnilembus persalinus. Environ Toxicol Pharmacol, 2017; 56: 35-42.
18. Ambili TR, Saravanan M, Ramesh M, Abhijith RK, Poopal. Toxicological Effects of the Antibiotic Oxytetracycline to an Indian Major Carp Labeo rohita. Arch Environ Contam Toxicol 2012; 64:494-503.
19. Gunes A, Ataoglu N, Turan M, Esitken A, Quirine M. Effects of phosphate- solubilising microorganisms on strawberry yield and nutrient concentrations. J Plant Nutrition Soil Science 2009; 172(3).
20. Shales DM. An update on tetracycline. Curr opin investing Drugs 2007; 7: 167-171.
21. Moffat AC, Osselton MD, Widdop B. (2011). Clarke's Analysis of Drugs and Poisons: in Pharmaceuticals, Body Fluids and Postmortem Material. 4th ed; Pharmaceutical Press: London.
22. Chartone-Souza E, Loyola TL, Rodriguez M, Menezes MA, Rey NA, Pereira-Maia EC. Synthesis and characterization of a Tetracycline-Platinum (II) Complex Active Against Resistant Bacteria. J. Inorg. Biochem 2005; 99: 1001–1008.
23. Kay P, Blackwell PA, Boxall AB. Fate of veterinary antibiotics in a macroporous tile drained clay soil. Environ. Toxicol. Chem 2004; 23: 1136–1144.
24. Boxall AB, Fogg LA, Blackwell PA, Kay P, Pemberton EJ, Croxford A. Veterinary medicines in the environment. Rev Environ Contam Toxicol 2004; 180:1–91.
25. Bjorklund H, Bondestam J, Bylund G. Residues of oxytetracycline in wild ?sh and sediments from ?sh farms. Aquaculture 1990; 86:359–367.
26. Olatoye IO, Basiru A. Antibiotics usage and oxytetracycline residue in african catfish(Clarias gariepinus) in Ibadan, Nigeria. World J fish marine sci 2013; 5 :302-309.
27. Barani A, fallah AA. Occurance of tetracycline, sulfonamides, fluoroquinolones and florefenicol in formed rainbow trout in Iran 2014; 26, 420-429.
28. Baydon E, kaya S, cergirgan H, Yildirim E, Altintast Yurdakok B, Ekici H, Aydin FG, Kucukosmanoglu AG. Investigation of some veterinary drugs residues in sea water, sediments and wild fishes captured around fish farm in the Aegean Sea: Oxytetracycline, ivermectin and emamectin. Ankara Univ Vet Fak Derg 2015; 62: 171-176.
29. Kolpin DW, Furlong ET, Meyer MT, Thurman EM, Zaugg SD, Barber LB, Buxton HT. Pharmaceuticals, hormones, and other organic wastewater contaminants in U.S. streams, 1999- 2000: A national reconnaissance: Environmental Science & Technology 2002; 36(6): 1202-1211.
30. Thurman EM, Dietze JE, Scribner EA. Occurrence of antibiotics in water from fish hatcheries. Toxic Substance Hydrology Program. Technical Report USGS FS 2003;120-02.
31. Bebak-Williams J, Bullock G, Carson MC. Oxytetracycline residues in a freshwater recirculating system. Aquaculture 2002; 205:221– 230.
32. Samuelsen OB, Lunestad BT, Husevdg B, H~lleland, T, Ervik A. Residues of oxolinic acid in wild fauna following medication in fish farms. Dis aquat Org 1992; 12: 111-119.
33. Capone DG, Weston DP, Miller V, Shoemaker C. Antibacterial residues in marine sediments and invertebrates following chemotherapy in aquaculture. Aquaculture 1996; 145:55–75.
34. Coyne R, Hiney M, Smith P. Transient presence of oxytetracycline in blue mussels (Mytilus edulis) following its therapeutic use at a marine Atlantic salmon farm. Aquaculture 1997; 149: 175–181.
35. Penghua W, Pow-Seng Y, Lim TT. C–N–S tridoped TiO2 for photocatalytic degradation of tetracycline under visible-light irradiation. Appl Catal Gen. 2011; 399: 252–61. doi: 10.1016/j.apcata.2011.04.008.
36. Chen YS, Zhang HB, Luo YM, Song J. Occurrence and assessment of veterinary antibiotics in swine manures: a case study in East China. Chinese Sci Bull 2012; 201257, 606–614. doi: 10.1007/s11434-011-4830-3
37. Sarmah AK, Meyer MT, Boxall ABA. A global perspective on the use, sales, exposure pathways, occurrence, fate and effects of veterinary antibiotics (VAs) in the environment. Chemosphere. 2006; 65: 725–59. doi: 10.1016/j.chemosphere.2006.03.026.
38. Batt AL, Snow DD, Aga DS. Occurrence of sulphonamide antimicrobials in private water wells in Washington County, Idaho, USA. Chemosphere. 2006; 64: 1963–71. doi: 10.1016/j.chemosphere.2006.01.029
39. Wang B, Lv X.-L, Feng D, Xie L-H, Zhang J, Li M, Xie Y, Li J-R, Zhou H-C, 2016. Highly stable Zr (IV)-based metal–organic frameworks for the detection and removal of antibiotics and organic explosives in water. J. Am. Chem. Soc. 138, 6204–6216.
40. Naik L, Sharma R, Mann B, Lata K, Rajput YS, Nath BS. Rapid screening test for detection of oxytetracycline residues in milk using lateral flow assay. Food Chem. 2017; 219: 85–92
41. Fatta-Kassinos D, Meric S, Nikolaou A. Pharmaceutical residues in environmental waters and wastewater: current state of knowledge and future research. Anal. Bioanal. Chem. 2011; 399: 251–275.
42. Javid A, Mesdaghinia A, Nasseri S, Mahvi AH, Alimohammadi M, Gharibi H. Assessment of tetracycline contamination in surface and groundwater resources proximal to animal farming houses in Tehran, Iran. Journal of Environmental Health Science & Engineering 2016 14:4 DOI 10.1186/s40201-016-0245-z
43. Pazdro K, Borecka M, Siedlewicz G, Bia?k-Bieli ?nska A, Step- nowski P. Analysis of the Residues of Pharmaceuticals in Marine Environment: State-of-the-art, Analytical Problems and Challenges. Curr. Anal. Chem. 2016; 12 (3): 202—226
44. Siedlewicz G, Borecka M, Bia?k-Bieli ?nska A, Sikora K, Step- nowski P, Pazdro K. Determination of antibiotic residues in southern Baltic Sea sediments using a tandem solid- phase extraction and liquid chromatography coupled with tan- dem mass spectrometry. Oceanologia 2016 58 (3), 221—234, https: //
45. KPMG International.The Indian Pharmaceutical Industry: Collaboration for Growth. 2006; 2-42
46. Subedi B, Balakrishna K, Sinha R, Yamashita N, Balasubramanian V, Kannan K. Mass loading and removal of pharmaceuticals and personal care products, including psychoactive and illicit drugs and artificial sweeteners, infive sewage treatment plants in India. J Environ Chem Eng 2015; 3: 2882–2891.
47. Akiba M, Senba H, Otagiri H, Prabhasankar V, Taniyasu S, Yamashita N, Lee K,Yamamoto T, Tsutsui T, Ian Joshua D, Balakrishna K, Bairy I, Iwata T, Kusumoto M, Kannan K, Guruge K. Impact of wastewater from differentsources on the prevalence of antimicrobial-resistant Escherichia coli in sewagetreatment plants in South India. Ecotoxicol Environ Saf 2015; 115, 203–208.
48. Archana G, Dhodapakar R, Kumar A. Offline solid-phase extraction forpreconcentration of pharmaceuticals and personal care products in environmentalwater and their simultaneous determination using the reversed phase high-performance liquid chromatography method. Environ. Monit Assess 2016; 188: 512–522.
49. Klajn R. (2001). Tetracycline: Chemistry and Chemical Biology of Tetracyclines.
50. Hash JH, Wishnick M, Miller PA. On the mode of action of the tetracycline antibiotics in Staphylococcus aureus. J Biol Chem 1964; 239: 2070–2078.
51. Semenkov YuP, Makarov EM, Makhno, Kirillov SV. Kinetic aspects of tetracycline action on the acceptor (A) site of Escherichia coli ribosomes. FEBS Lett 1982; 144: 125–129.
52. Yamaguchi A, Udagawa T, Sawai T. Transport of divalent cations with tetracycline as mediated by the transposon Tn10-encoded tetracycline resistance protein. J Biol Chem 1990; 265: 4809–4813.
53. Singh AK, Rathore G, Singh V, Mani I, Singh RK, Mishra SK. Bacterial resistance to oxytetracycline in different life stages of Indian freshwater carp aquaculture system. Int J Microbiol Res 2009; 1(1): 25–34.
54. Samanidou VF, Evaggelopoulou EN. Analytical strategies to determine antibiotic residues in fish. J Sep Sci 2007; 30: 2549-2569.

55. Guardiola FA, Cerezuela R, Meseguer J, Esteban MA. Modulation of the immune parameters and expression of genes of gilthead seabream (Sparus aurata L.) by dietary administration of oxytetracycline. Aquaculture 2012; 334–337:51–57
56. Hentschel DM, Park KM, Cilenti L, Zervos AS, Drummond I, Bonventre JV. Acute renal failure in zebrafish: A novel system to study a complex disease. Am J Physiol Renal Physiol 2005; 288: F923-F929.
57. Santos LH, Araújo AN, Fachini A, Pena A, Delerue-Matos C, Montenegro MC. Ecotoxicological aspects related to the presence of pharmaceuticals in the aquatic environment. J. Hazard Mater 2010; 175 (1–3): 45–95.
58. Lionetto MG, Caricato R, Calisi A, Giordano ME, Schettino T. Acetylcholinesterase as a biomarker in environmental and occupational medicine: new insights and future perspectives. Bio Med Res Int 2013; 321: 1–8.
59. Ren X, Wang Z, Gao B, Liu P, Li J. Toxic responses of swimming crab (Portunus trituberculatus) larvae exposed to environmentally realistic concentrations of oxytetracycline. Chemosphere 2017; 173: 563–571.
60. Limbu SM, Zhou L, Sun SX, Zhang ML, Du ZY. Chronic exposure to low environmental concentrations and legal aquaculture doses of antibiotics cause systemic adverse e?ects in Nile tilapia and provoke di?erential human health risk. Environ Int 2018; 115, 205–219.
61. Micale V, Pirrera L, Bottari T, Busalacchi B, Perdicihzzi A, Perdichizzi F, Profeta A, Rinelli P, Corsi I. A Multimarkers approach to assess the environmental pollution on biological resources subject of commercial ?shing: the case of Mullus barbatus (Linnaeus, 1758) in the southern Tyrrhenian Sea. In: Book: Marine Research at CNR, Fishery and Sea Resources 2011; 2083–2098.
62. Rodrigues S, Antunes SC, Correia AT, Nunes B. Rainbow trout (Oncorhynchus mykiss) pro-oxidant and genotoxic responses following acute and chronic exposure to the antibiotic oxytetracycline. Ecotoxicology 2017; 26: 104–117.
63. K?adna A, Michalska T, Berczy?ski P, Kruk I, Aboul?Enein HY. Evaluation of the antioxidant activity of tetracycline antibiotics in vitro. J Bio and Chem Luminecence 2012:27(4); 249-254
64. Khan MA, Mustafa J, Musarrat J. Mechanism of DNA strand breakage induced by photosensitized tetracycline-Cu (II) complex. Mutat Res 2003; 525: 109–119.
65. Rodrigues Sara, Antunes Sara C, Bruno N, Teodorico, CA. HistopathologicaleffectsingillsandliverofSparusauratafollowing acute and chronic exposures to erythromycin and oxytetracycline. Environ Sci Pollu Res 2019; 3810-193.
66. Botelho RG, Christofoletti CA, Correia JE, Ansoar Y, Olinda RA, Tornisielo VL. Genotoxic responses of juvenile tilapia (Oreochromis niloticus) exposed to ?orfenicol and oxytetracycline. Chemosphere 2015; 132: 206–212.
67. Said AA, Matsuki N, Kasuya Y. E?ects of aminoglycoside antibiotics on cholinergic autonomic nervous transmission. Pharmacol. Toxicol 1995; 76 (2): 128–132.
68. Nazeri S, Farhangi M, Modarres S. The effect of different dietary inclusion levels of rutin (a flavonoid) on some liver enzyme activities and oxidative stress indices Fin rainbow trout, Oncorhynchus mykiss (Walbaum) exposed to oxytetracycline. Aquac Res 2017; 48: 4356–4362.
69. Yonar ME, Yonar SM, Silici S. Protective effect of propolis against oxidative stress and immune suppression induced by oxytetracycline in rainbow trout (Oncorhynchus mykiss, W.). Fish Shellfish Immun 2011; 31:318–325.
70. Liu J, Lu G, Cai Y, Wu D, Yan Z, Wang Y. Modulation of erythromycin-induced biochemicalresponses in crucian carpbyketoconazole. Environ Sci Pollut Res 2017; 24: 5285–5292.
71. Oliveira R, McDonough S, Ladewig JC, Soares AM, Nogueira AJ, Domingues I. E?ects of oxytetracycline and amoxicillin on development and biomarkers activities of zebra?sh (Danio rerio). Environ. Toxicol Pharmacol 2013; 36 (3): 903–912.
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How to Cite
Sharma, M. “TOXIC EFFECT OF PHARMACEUTICALS WITH REFERENCE TO OXYTETRACYCLIN: Toxicity of Pharmaceuticals”. Asian Journal of Pharmaceutical and Clinical Research, Vol. 14, no. 1, Jan. 2021, pp. 64-68,
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