Abstract
Acute toxicities of chloramphenicol (CAP), thiamphenicol (TAP), and florfenicol (FLO) and their mixtures on Daphnia magna under two representative temperatures of the aquatic environment (20 and 25 °C) have been examined. Their toxicities depicted with an order of 72-h EC50 values were as follows: CAP > FLO > TAP and CAP ≈ FLO > TAP under 20 and 25 °C, separately. Furthermore, the acute toxicity significantly increased with the rise of temperature from 20 to 25 °C in nearly all separate and mixture phenicol antibiotics. Meanwhile, the most toxic combination under two different temperatures was diverse. The nature of toxicological interactions of phenicol antibiotic mixtures was analyzed by Combination Index (CI) equation. In general, a dual synergism-antagonism effect was dominant in nearly all mixtures at both temperatures. The prediction suitability of Concentration Addition (CA), Independent Action (IA) models, and CI method was compared, suggesting that the CI equation seems to be more appropriate for predicting the toxicity values of phenicol drugs than CA and IA models. In brief, phenicol antibiotic mixtures with temperature variation may pose more significant hazards and risks to aquatic organisms; hence, the environment.
Similar content being viewed by others
Change history
21 January 2021
A Correction to this paper has been published: https://doi.org/10.1007/s10646-021-02347-z
References
Altenburger R, Walter H, Grote M (2004) What contributes to the combined effect of a complex mixture? Environ Sci Technol 38(23):6353–6362
Anadón A, Bringas P, Martinez-Larrañaga MR, Diaz MJ (1994) Bioavailability, pharmacokinetics and residues of chloramphenicol in the chicken. J Vet Pharmacol Ther 17(1):52–58
Bae E, Samanta P, Yoo J, Jung J (2016) Effects of multigenerational exposure to elevated temperature on reproduction, oxidative stress, and Cu toxicity in Daphnia magna. Ecotoxicol Environ Saf 132:366–371
Berthoud H (2013) Synergy: a Concept in Search of a Definition. Endocrinology 154(11):3974–3977
Bliss CI (1939) The Toxicity of Poisons Applied Jointly. Ann Appl Biol 26(3):585–615
Boltes K, Rosal R, García-Calvo E (2012) Toxicity of mixtures of perfluorooctane sulphonic acid with chlorinated chemicals and lipid regulators. Chemosphere 86(1):24–29
Dalla Bona M, Lizzi F, Borgato A, De Liguoro M (2016) Increasing toxicity of enrofloxacin over four generations of Daphnia magna. Ecotoxicol Environ Saf 132:397–402
Carusso S, Juárez AB, Moretton J, Magdaleno A (2018) Effects of three veterinary antibiotics and their binary mixtures on two green alga species. Chemosphere 194:821–827
Cedergreen N, Christensen AM, Kamper A, Kudsk P, Mathiassen SK, Streibig JC, Sørensen H (2008) A review of independent action compared to concentration addition as reference models for mixtures of compounds with different molecular target sites. Environ Toxicol Chem 27(7):1621–1632
Chen C, Wang YH, Qian YZ, Zhao XP, Wang Q (2015) The synergistic toxicity of the multiple chemical mixtures: implications for risk assessment in the terrestrial environment. Environ Int 77:95–105
Choi K, Kim Y, Jung J, Kim MH, Kim CS, Kim NH, Park J (2008) Occurrences and ecological risks of roxithromycin, trimethoprim, and chloramphenicol in the Han River, Korea. Environ Toxicol Chem 27(3):711–719
CompuSyn for Drug Combinations. PC Software and User’s Guide: A Computer Program for Quantitation of Synergism and Antagonism in Drug Combinations, and the Determination of IC50, ED50, and LD50 Values, ComboSyn Inc, Paramus, NJ. http://www.combosyn.com
Chou TC (2006) Theoretical basis, experimental design, and computerized simulation of synergism and antagonism in drug-combination studies. Pharmacol Rev 58(3):621–628
Chou TC, Talalay P (1984) Quantitative analysis of dose-effect relationships: the combined effects of multiple drugs or enzyme inhibitors. Adv Enzyme Regul 22(84):27–55
Christensen AM, Ingerslev F, Baun A (2006) Ecotoxicity of mixtures of antibiotics used in aquacultures. Environ Toxicol Chem 25(8):2208–2215
Cleuvers M (2003) Aquatic ecotoxicity of pharmaceuticals including the assessment of combination effects. Toxicol Lett 142(3):185–194
De Liguoro M, Riga A, Fariselli P (2018) Synergistic toxicity of some sulfonamide mixtures on Daphnia magna. Ecotox Environ Safe 164:84–91
Deng WJ, Li N, Zheng HL, Lin HY (2016) Occurrence and risk assessment of antibiotics in river water in Hong Kong. Ecotoxicol Environ Saf 125:121–127
Du J, Zhao HX, Liu SS, Xie HJ, Wang Y (2017) Antibiotics in the coastal water of the South Yellow Sea in China: occurrence, distribution and ecological risks. Sci Total Environ 595:521–527
European Commission (1996) Council Directive 96/23/EC of 29 April 1996. Off. J. Eur. Commun. 5:L125. (1996) 10
Flach AJ (1982) Fatal aplastic anemia following topical administration of ophthalmic chloramphenicol. Am J Ophthalmol 93(3):356–360
Flaherty CM, Dodson SI (2005) Effects of pharmaceuticals on Daphnia survival, growth, and reproduction. Chemosphere 61(2):200–207
Geiger E, Hornek-Gausterer R, Sacan MT (2016) Single and mixture toxicity of pharmaceuticals and chlorophenols to freshwater algae Chlorella vulgaris. Ecotoxicol Environ Saf 129:189–198
Gómez-Oliván LM, Galar-Martínez M, García-Medina S, Valdes-Alanis A, Islas-Flores H, Neri-Cruz N (2014) Genotoxic response and oxidative stress induced by diclofenac, ibuprofen and naproxen in Daphnia magna. Drug Chem Toxicol 37(4):391–399
González-Pleiter M, Gonzalo S, Rodea-Palomares I, Leganés F, Rosal R, Boltes K, Marco E, Fernández-Piñas F (2013) Toxicity of five antibiotics and their mixtures towards photosynthetic aquatic organisms: implications for environmental risk assessment. Water Res 47(6):2050–2064
Godoy A, Kummrow F (2017) What do we know about the ecotoxicology of pharmaceutical and personal care product mixtures? A critical review. Critic Rev Environ Sci Technol 47(16):1453–1496
Hamid N, Junaid M, Manzoor R, Jia PP, Pei DS (2020) Prioritizing Phthalate Esters (PAEs) using experimental in vitro/vivo toxicity assays and computational in silico approaches. J Hazard Mater 398:122851
Hadrup N, Taxvig C, Pedersen M, Nellemann C, Hass U, Vinggaard AM (2013) Concentration Addition, Independent Action and Generalized Concentration Addition Models for Mixture Effect Prediction of Sex Hormone Synthesis In Vitro. Plos ONE 8(8):e70490
Heugens EH, Jager T, Creyghton R, Kraak MH, Hendriks AJ, Van Straalen NM, Admiraal W (2003) Temperature-dependent effects of cadmium on Daphnia magna: accumulation versus sensitivity. Environ Sci Technol 37(10):2145–2151
International Organization for Standardization (1996) Water quality. Determination of the inhibition of the mobility of Daphnia magna Straus (Cladocera, Crustacea)- Acute toxicity test. International Organisation for Standardisation. Geneva, Switzerland
Jesús V, Georgiana A, Karina B, Maria ÁG, Maria LM (2019) Enantiomer stability and combined toxicity of duloxetine and econazole on Daphnia magna using real concentrations determined by capillary electrophoresis. Sci Total Environ 670:770–778
Jia J, Zhu F, Ma XH, Cao ZW, Li YX, Chen YZ (2009) Mechanisms of drug combinations: interaction and network perspectives. Nat Rev Drug Discov 8(2):111–128
Kim J, Park J, Kim PG, Lee C, Choi K, Choi K (2010) Implication of global environmental changes on chemical toxicity-effect of water temperature, pH, and ultraviolet B irradiation on acute toxicity of several pharmaceuticals in Daphnia magna. Ecotoxicology 19(4):662–669
Kristofco LA, Du BW, Chambliss CK, Berninger JP, Brooks BW (2015) Comparative Pharmacology and Toxicology of Pharmaceuticals in the Environment: Diphenhydramine Protection of Diazinon Toxicity in Danio rerio but Not Daphnia magna. AAPS J 17(1):175–183
Lai HT, Hou JH, Su CI, Chen CL (2009) Effects of Chlorarnphenicol, Florfenicol, and Thiamphenicol on Growth of Algae Chlorella Pyrenoidosa, Isochrysis Galbana, and Tetraselmis Chui. Ecotoxicol Environ Saf 72(2):329–334
Li WH, Gao LH, Shi YL, Liu JM, Cai YQ (2015) Occurrence, distribution and risks of antibiotics in urban surface water in Beijing, China. Environ Sci Process Impacts 17(9):1611–1619
Li X (2010) Toxic effects of florfenicol and its analogues to aquatic organisms (In Chinese). Dissertation. Jinan University, Guangzhou, China
Liu H, Zhang GP, Liu CQ, Li L, Xiang M (2009) The occurrence of chloramphenicol and tetracyclines in municipal sewage and the Nanming River, Guiyang City, China. J Environ Monit 11(6):1199–1205
Liu YM, Liu SH, Zhang H, Gu YP, Li XS, He MY, Tan HH (2017) Application of the combination index (CI)-isobologram equation to research the toxicological interactions of clothianidin, thiamethoxam, and dinotefuran in honeybee, Apismellifera. Chemosphere 184:806–811
Long X, Wang D, Lin Z, Qin M, Song C, Liu Y (2016) The mixture toxicity of environmental contaminants containing sulfonamides and other antibiotics in Escherichia coli: Differences in both the special target proteins of individual chemicals and their effective combined concentration. Chemosphere 158:193–203
Maceda-Veiga A, Webster G, Canals O, Salvadó H, Weightman AJ, Cable J (2015) Chronic effects of temperature and nitrate pollution on Daphnia magna: Is this cladoceran suitable for widespread use as a tertiary treatment? Water Res 83:141–152
Magdaleno A, Saenz ME, Juárez AB, Moretton J (2015) Effects of six antibiotics and their binary mixtures on growth of Pseudokirchneriella subcapitata. Ecotoxicol Environ Saf 113:72–78
Marcelina J, Wioletta P (2019) Ecotoxicity risk of presence of two cytostatic drugs: Bleomycin and vincristine and their binary mixture in aquatic environment. Ecotox Environ Safe 172:210–215
Marti E, Variatza E, Balcazar JL (2014) The role of aquatic ecosystems as reservoirs of antibiotic resistance. Trends Microbiol 22(1):36–41
Martins A, Guimarães L, Guilhermino L (2013) Chronic toxicity of the veterinary antibiotic florfenicol to Daphnia magna assessed at two temperatures. Environ Toxicol Pharmacol 36(3):1022–1032
Mccarty LS, Borgert CJ (2006) Review of the toxicity of chemical mixtures containing at least one organochlorine. Regul Toxicol Pharmacol 45(2):104–118
Mitchell SE, Lampert W (2000) Temperature adaptation in a geographically widespread zooplankter Daphnia magna. J Evol Biol 13(3):371–382
Nagata T, Oka H (1996) Detection of residual chloramphenicol, florfenicol, and thiamphenicol in yellowtail fish muscles by capillary gas chromatography-mass spectrometry. J Agric Food Chem 44(5):1280–1284
Nieto E, Blasco J, González-Ortegón E, Drake P, Hampel M (2013) Is Atyaephyra desmarestii a useful candidate for lethal and sub-lethal toxicity tests on pharmaceutical compounds? J Hazard Mater 263:256–265
Nieto E, Hampel M, González-Ortegón E, Drake P, Blasco J (2016) Influence of temperature on toxicity of single pharmaceuticals and mixtures, in the crustacean A. desmarestii. J Hazard Mater 313:159–169
Noyes PD, Mcelwee MK, Miller HD, Clark BW, Tiem LAV, Walcott KC, Erwin KN, Levin ED (2009) The toxicology of climate change: environmental contaminants in a warming world. Environ Int 35(6):971–986
Organization for Economic Co-operation and Development (2004) Guidelines for Testing of Chemicals. In Daphnia sp. Acute Immobilization Test. OECD, Paris
Organization for Economic Co-operation and Development (1997) Report of the final ring test of the Daphnia magna reproduction test; OECD Environmental Health and Safety Publications Series on Testing and Assessment 6., Vol. 16. OECD, Paris, France
Ou DY, Chen B, Chen CX, Chen XQ, Song PQ, Lin HS (2013) Distribution of antibiotics residue and resistant bacteria in the downstream and estuarine area in Jiulong River. China Environ Sci 33(12):2243–2250
Peng XZ, Wang ZD, Kuang WX, Tan JH, Li K (2006) A preliminary study on the occurrence and behavior of sulfonamides, ofloxacin and chloramphenicol antimicrobials in wastewaters of two sewage treatment plants in Guangzhou, China. Sci Total Environ 371(1-3):314–322
Pilehvar S, Gielkens K, Trashin SA, Dardenne F, Blust R, De Wael K (2015) Electro)Sensing of Phenicol Antibiotics - A Review. Crit Rev Food Sci Nutr 56(14):2416–2429
Ribeiro AR, Sures B, Schmidt TC (2018) Ecotoxicity of the two veterinarian antibiotics ceftiofur and cefapirin before and after photo-transformation. Sci Total Environ 619-620:866–873
Robinson AA, Belden JB, Lydy MJ (2005) Toxicity of fluoroquinolone antibiotics to aquatic organisms. Environ Toxicol Chem 24(2):423–430
Rodea-Palomares I, Petre AL, Boltes K, Leganés F, Antonio Perdigon-Melon J, Rosal R, Fernandez- Piñas F (2010) Application of the combination index (CI)-isobologram equation to study the toxicological interactions of lipid regulators in two aquatic bioluminescent organisms. Water Res 44(2):427–438
Rosal R, Rodea-Palomares I, Boltes K, Fernández-Piñas F, Leganés F, Petre A (2010). Ecotoxicological assessment of surfactants in the aquatic environment: Combined toxicity of docusate sodium with chlorinated pollutants. Chemosphere 81(2):288–293
Rose S, Altenburger R, Sturm A (2016) Mixture toxicity effects of sea louse control agents in Daphnia magna. Chemosphere 144:599–606
Santos LHML, Araújo AN, Fachini A, Pena A, Delerue-Matos C, Montenegro MCBSM (2010) Ecotoxicological aspects related to the presence of pharmaceuticals in the aquatic environment. J Hazard Mater 175(1-3):45–95
Seidl MD, Pirow R, Paul RJ (2005) Acclimation of the microcrustacean Daphnia magna to warm temperatures is dependent on haemoglobin expression. J Therm Biol 30(7):532–544
Sikkink KL, Ituarte CM, Reynolds R, Cresko WA, Phillips PC (2014) The transgenerational effects of heat stress in the nematode Caenorhabditis remanei are negative and rapidly eliminated under direct selection for increased stress resistance in larvae. Genomics 104(6):438–446
The Ministry of Agriculture PRC (2002) Establishment of maximum residue levels of veterinary medicinal products in foodstuffs of animal origin (In Chinese), Regulation No. 235 http://www.moa.gov.cn/gk/tzgg_1/gg/200302/t20030226_59300.htm
Trombini C, Hampel M, Blasco J (2016) Evaluation of acute effects of four pharmaceuticals and their mixtures on the copepod Tisbe battagliai. Chemosphere 155:319–328
Van Doorslaer X, Haylamicheal ID, Dewulf J, Van Langenhove H, Janssen CR, Demeestere K (2015) Heterogeneous photocatalysis of moxifloxacin in water: chemical transformation and ecotoxicity. Chemosphere 119:S75–S80
Van de Riet JM, Potter RA, Christie-Fougere M, Burns BG (2003) Simultaneous determination of residues of chloramphenicol, thiamphenicol, florfenicol, and florfenicol amine in farmed aquatic species by liquid chromatography/mass spectrometry. J Aoac Int 86(3):510–514
Viñas P, Balsalobre N, Hernández-Córdoba M (2006) Determination of chloramphenicol residues in animal feeds by liquid chromatography with photo-diode array detection. Anal Chim Acta 558(1-2):11–15
Wang MX, Zhang YX, Guo PY (2017) Effect of florfenicol and thiamphenicol exposure on the photosynthesis and antioxidant system of Microcystis flos-aquae. Aquat Toxicol 186:67–76
Wollenberger L, Halling-Sørensen B, Kusk KO (2000) Acute and chronic toxicity of veterinary antibiotics to Daphnia magna. Chemosphere 40(7):723–730
Xu LW, Liao CR, Liu GF (2005) Security about florfenicol used in aquaculture. J Fishery Sci China 12(4):512–518
Xiong Q, Hu LX, Liu YS, Wang TT, Ying GG (2019) New insight into the toxic effects of chloramphenicol and roxithromycin to algae using FTIR spectroscopy. Aquat Toxicol 207:197–207
Yiruhan, Wang QJ, Mo CH, Li YW, Gao P, Tai YP, Zhang Y, Ruan ZL, Xu JW (2010) Determination of four fluoroquinolone antibiotics in tap water in Guangzhou and Macao. Environ Pollut 158(7):2350–2358
Zhang QQ, Ying GG, Pan CG, Liu YS, Zhao JL (2015) Comprehensive evaluation of antibiotics emission and fate in the river basins of China: source analysis, multimedia modeling, and linkage to bacterial resistance. Environ Sci Technol 49(11):6772–6782
Zhang Q, Xin Q, Zhu JM, Cheng JP (2014) The antibiotic contaminations in the main water bodies in China and the associated environmental and human health impacts. Environ Chem 33(7):1075–1083
Zhang YX, Guo PY, Wu YM, Zhang XY, Wang MX, Yang SM, Sun YS, Deng J, Su HT (2019) Evaluation of the Subtle Effects and Oxidative Stress Response of Chloramphenicol, Thiamphenicol, and Florfenicol in Daphnia magna. Environ Toxicol Chem 38(3):575–584
Zong HM, Ma DY, Wang JY, Hu JT (2010) Research on Florfenicol Residue in Coastal Area of Dalian (Northern China) and Analysis of Functional Diversity of the Microbial Community in Marine Sediment. B Environ Contam Tox 84(2):245–249
Acknowledgements
This work is supported by the National Natural Science Foundation of China (No. 20777021), the Natural Science Foundation of Fujian Province of China (No. 2017J01018), and the Quanzhou City Science & Technology Program of China (No. 2018Z003).
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Conflict of interest
The authors declare that they have no conflict of interest.
Ethical approval
All applicable international, national, and/or institutional guidelines for the care and use of animals were followed.
Additional information
Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Supplementary information
Rights and permissions
About this article
Cite this article
Zhang, Y., Guo, P., Wang, M. et al. Mixture toxicity effects of chloramphenicol, thiamphenicol, florfenicol in Daphnia magna under different temperatures. Ecotoxicology 30, 31–42 (2021). https://doi.org/10.1007/s10646-020-02311-3
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s10646-020-02311-3