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Estimating combined health risks of nanomaterials and antibiotics from natural water: a proposed framework

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Abstract

Nanoparticles (NPs) are one of the major class of emerging contaminants identified in aquatic environment. There is a probability that they can co-exist with other chemical pollutants like antibiotics (ABs) as ABs-NPs complexes in natural water systems. If these complexes are taken up via inadvertent ingestion of contaminated water, it might show detrimental effects on human health. To address this challenging issue, this study developed a risk framework to assess the combined exposure of ABs and NPs in natural waters for the first time. The six-step framework was applied to a hypothetical exposure of NPs (copper oxide, CuO; zinc oxide, ZnO; iron oxide, Fe3O4; and titanium oxide, TiO2) and ABs (ciprofloxacin, CIP; ofloxacin, OFX; norfloxacin, NOR; and levofloxacin, LEVO) to estimate human health risks for two different exposure scenarios. Risk estimation was also conducted for the released fragments of ABs, NPs and metal ions in the human digestive system. Mixture toxicity risk assessment was conducted for three different combinations: (i) ABs and metal ions, (ii) ABs and NPs, and (iii) NPs and metals ions. Although the expected risk values were observed to be less than 1 (both hazard quotients and hazard interactions less than 1) for all the conditions and assumptions made, still a thorough monitoring and analysis of the studied contaminants in water is required to protect humans from their adverse effects, if any. Maximum allowable concentrations (Cmax) at which no risk can occur to humans was found to be (maximum values): ABs (233.8 µg/L, NOR); metal ions (1.02 × 109 mg/L, Ti2+ ions), and NPs (6.68 × 105 mg/L, TiO2), respectively.

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Data availability

All the data supporting the results reported in the article are included in the manuscript and can be found in supplementary file. Data sharing is not applicable to this article as no datasets were generated or analysed during the current study.

Abbreviations

ABs:

Antibiotics

ADD:

Average daily dose

ATSDR:

Agency for Toxic Substances and Disease Registry

BAF:

Bio-accessibility fraction

CDI:

Chronic daily intake

CuO:

Copper oxide

Fe3O4 :

Iron oxide

FQs:

Fluoroquinolones

FDA:

Food and Drug Administration

HQ:

Hazard quotient

HI:

Hazard interactions

IRIS:

Integrated Risk Information System

NPs:

Nanoparticles

OECD:

Organization for Economic Co-operation and Development

PNEC:

Predicted no-effect concentration

RfD:

Reference dose

TiO2 :

Titanium dioxide

USEPA:

United States Environmental Protection Agency

EU:

European Union

WoE:

Weight of evidence

WHO:

World Health Organization

ZnO:

Zinc oxide

References

  • Abo-Shama UH, El-Gendy H, Mousa WS, Hamouda RA, Yousuf WE, Hetta HF, Abdeen E (2020) Synergistics and antagonistic effect of metal NPs in combination with ABs against some reference strains of pathogenic microorganisms. Infect Drug Resist. 13:351–362

    Article  CAS  Google Scholar 

  • Argall JAW, Wright N, Mackway-Jones K, Jackson R (2003) A comparison of two commonly used methods of weight estimation. Arch Dis Child 88(9):789–790. https://doi.org/10.1136/adc.88.9.789

    Article  CAS  Google Scholar 

  • Aschberger K, Christensen FM, Rasmussen K, Jensen KA (2016) Feasibility and challenges of human health risk assessment for engineered nanomaterials. In: Engineered NPs and the environment: biophysicochemical processes and toxicity. 409–441. https://doi.org/10.1002/9781119275855.ch21

  • ATSDR (2005). Public health assessment guidance msanual. Public Health Service Agency for Toxic Substances and Disease Registry Atlanta, Georgia, 1–357 January

  • Azizi S, Mohamad M, Abdul Rahim R, Moghaddam AB, Moniri M, Ariff A, Saad WZ, Namvab F (2016) ZnO-Ag core–shell nanocomposite formed by green method using essential oil of wild ginger and their bactericidal and cytotoxic effects Appl. Surf Sci 384:517–524

    Article  CAS  Google Scholar 

  • Bergin IL, Witzmann FA (2013) Nanoparticle toxicity by the gastrointestinal route: evidence and knowledge gaps. Int J Biomed Nanosci Nanotechnol. 3(1–2): https://doi.org/10.1504/IJBNN.2013.054515

  • Bopp SK, Kienzler A, Richarz A-N, van der Linden SC, Paini A, Parissis N, Worth AP (2019) Regulatory assessment and risk management of chemical mixtures: challenges and ways forward. Crit Rev Toxicol. https://doi.org/10.1080/10408444.2019.1579169

    Article  Google Scholar 

  • Canesi L, Ciacci C, Balbi T (2015) Interactive effects of NPs with other contaminants in aquatic organisms: friend or foe? Mar Environ Res 111:128–134

    Article  CAS  Google Scholar 

  • Chen X, O’Halloran J, Jansen MAK (2016) The toxicity of zinc oxide NPs to Lemna minor (L.) is predominantly caused by dissolved Zn. Aquat Toxicol 174:46–53. https://doi.org/10.1016/j.aquatox.2016.02.012

    Article  CAS  Google Scholar 

  • Coll C, Notter D, Gottschalk F, Sun T, Som C, Nowack B (2016) Probabilistic environmental risk assessment of five nanomaterials (nano-TiO2, nano-Ag, nano-ZnO, CNT, and fullerenes). Nanotoxicology 10(4):436–444

    Article  CAS  Google Scholar 

  • Croteau MN, Misra SK, Luoma SN, Valsami-Jones E (2014) Bioaccumulation and toxicity of CuO nanoparticles by a freshwater invertebrate after waterborne and dietborne exposures. Environ Sci Technol 48(18):10929–10937. https://doi.org/10.1021/es5018703

    Article  CAS  Google Scholar 

  • Cunningham VL, Binks SP, Olson MJ (2009) Human health risk assessment from the presence of human pharmaceuticals in the aquatic environment. Regul Toxicol Pharm 53:39–45

    Article  CAS  Google Scholar 

  • Ding W, Guo L (2013) Immobilized transferrin Fe3O4@SiO2 nanoparticle with high doxorubicin loading for dual-targeted tumor drug delivery. Int J Nanomed 8:4631–4639

    Google Scholar 

  • Djurdjevic P, Joksovic L, Jelic R, Djurdjevic A, Stankov MJ (2007) Solution equilibria between aluminium (III) ion and some fluoroquinolone family members. Spectroscopic and potentiometric study. Chem Pharm Bull 55:1689–1699

    Article  CAS  Google Scholar 

  • Ebele AJ, Abdallah M, A-E., Harrad, S. (2017) Pharmaceuticals and personal care products (PPCPs) in the freshwater aquatic environment. Emerging Contaminants 3(1):1–16

    Article  Google Scholar 

  • Evangelou MW, Ebel M, Schaeffer A (2007) Chelate assisted phytoextraction of heavy metals from soil. Effect, mechanism, toxicity, and fate of chelating agents. Chemosphere 68:989–1003. https://doi.org/10.1016/j.chemosphere.2007.01.062

    Article  CAS  Google Scholar 

  • Hamed SM, Elkhatib WF, El-Mahallawy HA et al (2018) Multiple mechanisms contributing to ciprofloxacin resistance among Gram negative bacteria causing infections to cancer patients. Sci Rep 8:12268

    Article  Google Scholar 

  • Hanna N, Sun P, Sun Q, Li X, Yang X, Ji X, Zou H, Ottoson J, Nilsson LE, Berglund B, Dyar OJ, Tamhankar AJ, Lundborg CS (2018) Presence of antibiotic residues in various environmental compartments of Shandong province in eastern China: its potential for resistance development and ecological and human risk. Environ Int 114:131–142

    Article  CAS  Google Scholar 

  • Hartmann NB, Baun A (2010) The nano cocktail: ecotoxicological effects of engineered nanoparticles in chemical mixtures. Integr Environ Assess Manag 6:311–313

    Article  Google Scholar 

  • Holden PA, Klaessig F, Turco RF, Priester J, Rico CM, Arias HA, Mortimer M, Pacpaco K, Gardea-Torresdey JL (2014) Evaluation of exposure concentrations used in assessing manufactured nanomaterial environmental hazards: are they relevant? Environ Sci Technol. https://doi.org/10.1021/es502440s

    Article  Google Scholar 

  • Hooper DC, Rubinstein E (2003) Quinolone antimicrobial agents. ASM Press, Washington, D.C.

    Book  Google Scholar 

  • IRIS (2005). Zinc and compounds (CASRN 7440–66–6). U.S. Environmental Protection Agency, pp. 1–21. http://www.epa.gov/iris/subst/0426.htm. Accessed 06 Feb 2021

  • Kumar A, Kumar P, Anandan A, Fernandes TF, Ayoko GA, Biskos G (2014) Engineered nanomaterials: knowledge gaps in fate, exposure, toxicity, and future directions. J. Nanomater 5

  • Kumari M, Kumar A (2020a) Human health risk assessment of antibiotics in binary mixtures for finished drinking water. Chemosphere 240:124864. https://doi.org/10.1016/j.chemosphere.2019.124864

    Article  CAS  Google Scholar 

  • Kumari M, Kumar A (2020b) Identification of component-based approach for prediction of joint chemical mixture toxicity risk assessment with respect to human health: A critical review. Food Chem Toxicol 143:111458. https://doi.org/10.1016/j.fct.2020.111458

  • Kumari M, Gupta SK (2018) Age dependent adjustment factor (ADAF) for the estimation of cancer risk through trihalomethanes (THMs) for different age groups- a innovative approach. Ecotox Environ Saf 148:960–968

    Article  CAS  Google Scholar 

  • Kumari M, Gupta SK, Mishra BK (2015) Multi-exposure cancer and non-cancer risk assessment of trihalomethanes in drinking water supplies – a case study of Eastern region of India. Ecotox Environ Saf 113:433–438

    Article  CAS  Google Scholar 

  • Kurlanda-Witek H, Ngwenya BT, Butler IB (2014) Transport of bare and capped zinc oxide nanoparticles is dependent on porous medium composition. J Contam Hydrol 162–163:17–26. https://doi.org/10.1016/j.jconhyd.2014.04.002

    Article  CAS  Google Scholar 

  • Lammel T, Wassmur B, Mackevica A, Chen L, Chang-Er., Sturve, J. (2019) Mixture toxicity effects and uptake of titanium dioxide (TiO2) nanoparticles and 3,3′,4,4′-tetrachlorobiphenyl (PCB77) in juvenile brown trout following co-exposure via the diet. Aquatic Toxicology 213:105195

    Article  CAS  Google Scholar 

  • Li J, Song Y, Vogt RD, Liu Y, Luo J, Li T (2020) Bioavailability and cytotoxicity of cerium-(IV), copper-(II), and zinc oxide nanoparticles to human intestinal and liver cells through food. Sci Total Environ. 702 https://doi.org/10.1016/j.scitotenv.2019.134700

  • Lubasch A, Keller I, Borner K, Koeppe P, Lode H (2000) Comparative Pharmacokinetics of Ciprofloxacin, Gatifloxacin, Grepafloxacin, Levofloxacin, Trovafloxacin, and Moxifloxacin after Single Oral Administration in Healthy Volunteers. Antimicrob Agents Chemother 44(10):2600–2603. https://doi.org/10.1128/AAC.44.10.2600-2603.2000

    Article  CAS  Google Scholar 

  • Menard A, Drobne D, Jemec A (2011) Ecotoxicity of nanosized TiO2. Review of in vivo data. Environ Pollut 159:677–684

    Article  CAS  Google Scholar 

  • Naasz S, Altenburger R, Kühnel D (2018) Environmental mixtures of nanomaterials and chemicals: the Trojan-horse phenomenon and its relevance for ecotoxicity. Sci Total Environ 635(1):1170–1181

    Article  CAS  Google Scholar 

  • Namvar F, Rahman HS, Mohamad R, Baharara J, Mahdavi M, Amini E, Yeap SK (2014) Cytotoxic effect of magnetic iron oxide nanoparticles synthesized via seaweed aqueous extract. Int J Nanomedicine 9:2479–2488. https://doi.org/10.2147/IJN.S59661

    Article  Google Scholar 

  • Nazari Z, Banoee M, Sepahi AK, Rafii F, Shahverdi. (2012) The combination effects of trivalent gold ions and gold nanoparticles with different antibiotics against resistant Pseudomonas aeruginosa. Gold Bull 45:53. https://doi.org/10.1007/s13404-012-0048-7

    Article  CAS  Google Scholar 

  • Owens RC, Patel KB, Banevicius MA, Quintiliani R, Nightangle CH, Nicolau DP (1997) Oral bioavailability and pharmacokinetics of Ciprofloxacin in patients with AIDS. Antimicrob Agents Ch 1508–1511

  • Pandurangan M, Kim DH (2015) In vitro toxicity of zinc oxide nanoparticles: a review. J Nanopart Res 17: Artn 158. https://doi.org/10.1007/S11051-015-2958-9

  • Parsai T, Kumar A (2020) Tradeoff between risks through ingestion of nanoparticle contaminated water or fish: human health perspective. Sci Total Environ 740:140140

  • Parsai T, Kumar A (2021) Setting guidelines for co-occurring nanoparticles in water medium. Sci Total Environ 776:145175

  • Peterson E, Kaur P (2018) Antibiotic resistance mechanisms in bacteria: relationships between resistance determinants of antibiotic producers, environmental bacteria, and clinical pathogens. Front Microbiol 9:2928

    Article  Google Scholar 

  • Pizzol L, Hristozov D, Zabeo A, Basei G, Wohlleben W, Koivisto AJ, Jensen KA, Fransman W, Stone V, Marcomini A (2019) SUNDS probabilistic human health risk assessment methodology and its application to organic pigment used in the automotive industry. NanoImpact 13:26–36. https://doi.org/10.1016/j.impact.2018.12.001

    Article  Google Scholar 

  • Preston RJ (2004) Children as a sensitive subpopulation for the risk assessment process. Toxicol Appl Pharmacol 199(2):132–141

    Article  CAS  Google Scholar 

  • Ramoju S, Andersen ME, Nong A, Karyakina N, Shilnikova N, Krishnan K, Krewski D (2020) Derivation of whole blood biomonitoring equivalents for titanium for the interpretation of biomonitoring data. Regul Toxic Pharmacol 114:104671

    Article  CAS  Google Scholar 

  • Seedher N, Agarwal P (2010) Effect of metal ions on some pharmacologically relevant interactions involving fluoroquinolone antibiotics. Drug Metab Drug Interact 25(1–4):17–24. https://doi.org/10.1515/DMDI.2010.003

    Article  CAS  Google Scholar 

  • Sharma PC, Jain A, Jain S, Pahwa R, Yar MS (2010) Ciprofloxacin: review on developments in synthetic, analytical, and medicinal aspects. J Enzyme Inhib Med Chem 25(4):577–589

    Article  CAS  Google Scholar 

  • Sharma D, Patel RP, Zaidi STR, Sarker MR, Lean QY, Ming LC (2017) Interplay of the quality of ciprofloxacin and antibiotic resistance in developing countries. Front Microbiol 8:546

    Google Scholar 

  • Shukla RK, Kumar A, Gurbani D, Pandey AK, Singh S, Dhawan A (2013) TiO2 nanoparticles induce oxidative DNA damage and apoptosis in human liver cells. Nanotoxicology 7(1):48–60. https://doi.org/10.3109/17435390.2011.629747

  • Snyder-Talkington N, Qian Y, Castranova V, Guo NL (2012) New perspectives for in vitro risk assessment of multiwalled carbon nanotubes: application of co-culture and bioinformatics. J Toxicol Environ Health B 15:468–492

    Article  CAS  Google Scholar 

  • Sukul P, Spiteller M (2007) Fluoroquinolone antibiotics in the environment. Rev Environ Contam Toxicol 191:131–162. https://doi.org/10.1007/978-0-387-69163-3_5

    Article  CAS  Google Scholar 

  • Thai T, Salisbury BH, Zito PM Ciprofloxacin [Updated 2021 Jul 7]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2021 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK535454/

  • Turel (2002) The interactions of metal ions with quinolone antibacterial agents. Coord Chem Rev 232(1–2):27–47

    Article  CAS  Google Scholar 

  • Twining J, McGlinn P, Loi E, Smith K, Giere R (2005) Risk ranking of bioaccessible metals from fly ash dissolved in simulated lung and gut fluids. Environ Sci Technol 39:7749–7756. https://doi.org/10.1021/es0502369

    Article  CAS  Google Scholar 

  • Urbaniak B, Mrestani Y, Kokot ZK, Neubert RH (2007) Investigation of interaction of fluoroquinolones with aluminium, iron and magnesium ions using capillary zone electrophoresis. Chromatographia 65:489–492

    Article  CAS  Google Scholar 

  • US EPA (Environmental Protection Agency) (2005). Drinking water standards and health advisories. Office of Water, Washington, DC. Available at http://www.epa.gov/ost/drinking/standards/dwstandards.pdf. Accessed 18 Feb 2021

  • US EPA (Environmental Protection Agency) (2006a). Integrated risk information system (IRIS). Online. Office of Research and Development. National Center for Environmental Assessment, Washington, D.C. www.epa.gov/iris. Accessed 01 Mar 2021

  • US EPA (Environmental Protection Agency) (2006b). Provisional peer reviewed toxicity values for iron and compounds (CASRN 7439–89–6). Derivation of subchronic and chronic oral RfDs

  • US EPA (U.S. Environmental Protection Agency) (2009a) Risk Assessment Guidance for Superfund vol I: human health evaluation manual (Part F, Supplemental Guidance for Inhalation Risk Assessment). Office of Superfund Remediation and Technology Innovation, Washington DC

  • US EPA (U.S. Environmental Protection Agency) (2009b) Risk Assessment Guidance for Superfund volume 1: human health evaluation manual (Part F, Supplemental Guidance for Dermal Risk Assessment). Office of Superfund Remediation and Technology Innovation, Washington DC

  • Uwizeyimana H, Wang M, Chen W, Khan K (2017) The eco-toxic effects of pesticide and heavy metal mixtures towards earthworms in soil. Environ Toxicol Pharmacol. https://doi.org/10.1016/j.etap.2017.08.001

    Article  Google Scholar 

  • Vergalli J, Atzori A, Pajovic J et al (2020) The challenge of intracellular antibiotic accumulation, a function of fluoroquinolone influx versus bacterial efflux. Commun Biol 3:198

    Article  CAS  Google Scholar 

  • Wang XH, Qu RJ, Liu JQ, Wei ZB, Wang LS, Yang SG et al (2016) Effect of different carbon nanotubes on cadmium toxicity to Daphnia magna: the role of catalyst impurities and adsorption capacity. Environ Pollut 208:732–738

    Article  CAS  Google Scholar 

  • Wang H, Tang C, Yang J, Wang Na, Jiang F, Xia Q, He G, Chen Y, Jiang Q (2018) Predictors of urinary ABs in children of Shanghai and health risk assessment. Environ Int 121:507–514

    Article  CAS  Google Scholar 

  • Wingender W, Forster D, Beermann D, Rohwedder R, Graefe KH, Schacht P (1985) Effect of gastric emptying time on rate and extent of the systemic availability of ciprofloxacin in humans. In Recent Advances in Chemotherapy, Antimicrobial section, ed. Ishigami, J., 1585- 1586. University of Tokyo Press

  • Yang J, Cao W, Rui Y (2017) Interactions between NPs and plants: phytotoxicity and defense mechanisms. J Plant Interact 12:158–169

    Article  CAS  Google Scholar 

  • Ye N, Wang Z, Wang Se, Fang H, Wang D (2018) Dissolved organic matter and aluminum oxide NPs synergistically cause cellular responses in freshwater microalgae. J Environ Sci Health 53:651–658

    Article  CAS  Google Scholar 

  • Zhong L, Yu Y, Lian H-z, Hu X, Fu H, Chen Yi-j (2017) Solubility of nano-sized metal oxides evaluated by using in vitro simulated lung and gastrointestinal fluids: implication for health risks. J Nanopart Res. 19 (11). https://doi.org/10.1007/s11051-017-4064-7

  • Zhu XS, Zhou J, Cai ZH (2011) TiO2 NPs in the marine environment: impact on the toxicity of tributyltin to abalone (Haliotis diversicolor supertexta) embryos. Environ Sci Technol 45:3753–3758

    Article  CAS  Google Scholar 

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Acknowledgements

This research work was conducted by author Dr. Minashree Kumari as a part of her Institute Post-Doctoral Fellowship in the Department of Civil Engineering at Indian Institute of Technology, Delhi (IIT Delhi), India. The authors wish to acknowledge IIT Delhi for supporting this research.

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  1. Environment Engineering Section, Department of Civil Engineering, Indian Institute of Technology Delhi, Hauz Khas, Delhi, 110016, India

    Minashree Kumari & Arun Kumar

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  1. Minashree Kumari
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Minashree Kumari (Draft writing, analysis, data interpretation, and editing), Arun Kumar (Supervision, conceptualisation, and editing).

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Correspondence to Minashree Kumari.

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Kumari, M., Kumar, A. Estimating combined health risks of nanomaterials and antibiotics from natural water: a proposed framework. Environ Sci Pollut Res 29, 13845–13856 (2022). https://doi.org/10.1007/s11356-021-16795-x

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