3rd World Conference on Applied Sciences, Engineering & Technology 27-29 September 2014, Kathmandu, Nepal Environmental Risks of Some Non-steroidal Anti-inflammatory
Drugs (NSAIDs) in Surface Water in Ho Chi Minh City
1Institute of Environmental Technology, Vietnam Academy of Science and Technology, Vietnam 2Vietnam Institute for Tropical Technology and Environmental Protection, Ho Chi Minh City, Vietnam E-mail: [email protected] Abstract: An environmental risk assessment of some common NSAIDs including ketoprofen, ibuprofen,
diclofenac sodium and mefenamic acid for surface water in Ho Chi Minh City was performed by determination
of their concentrations in water environment (MEC). Risk levels were obtained from the comparison between
the MEC value and predicted no-effect concentration (PNEC). Analysis results of the surface water samples
collected in Ho Chi Minh City during September, October and November 2013 showed that the environmental
risk levels of ketoprofen, ibuprofen and diclofenac sodium were not high except for ibuprofen at Le Van Sy
Bridge in the first two surveys. Mefenamic acid has consistently been identified as high risk at almost all
sampling sites. The total risk level of the 4 compounds in surface water in Ho Chi Minh City has been found at
high risk levels.According to the hazard index (HI) values calculated from chronic daily intake (CDI) and
reference dose (RfD), however, it is clear that the studied compounds at the existing concentrations cannot pose
negative impacts on human health even if the surface water is used for domestic water supply purpose. In the
long run, however, if the use of these compounds increase and no proper management measures are applied,
their residues in surface water may become a serious problem.

Keywords: Environmental Risk Assessment, Non-Steroidal Anti-Inflammatory Drugs (Nsaids), Surface Water

1. Introduction:
Pharmaceuticals and Personal Care Products (PPCPs)
residues present in the environment are now common
and recognized as a problem. Thousands of ton of
pharmacologically active substances are used every
year over the world to fight diseases or to face the
stresses of modern life. Studies conducted in
Germany, Greece, Italy, Spain, Switzerland, the Netherlands and the United States had found the presence of more than 80 compounds including pharmaceuticals and its metabolites in aquatic environment [1]. Notably, Non-Steroidal Anti- Inflammatory Drugs (NSAIDs) from various sources has been increasingly identified in the environment. Figure 1. Sampling sites
These NSAIDs account for many cases of ulcers and Samples were collected at the depth of 0.25 to 1.0 intestinal perforation in chronic users for pain and meter from the surface of water and stored in 2.5-liter inflammation. Therefore, PPCPs in general and amber glass bottles at 4 0C until sample treatment [4]. NSAIDs residues in particular in the environment, especially in water environment, should gain more 2.2. Sample preparation and analysis [5]
attention from us all. In fact, NSAIDs residues have 2.2.1. Chemicals and instrument:
been intensively studied around the world whereas Acetic acid (Merck), acetonitrile (Labscan), n-hexane they are still quite new to Vietnam. Subsequently, an (Labscan), methanol (Merck), ethyl acetate (Merck), environmental riskassessment of most commonly ultrapure water (Millipore), ketoprofen, ibuprofen, Anti-inflammatory diclofenac sodium and mefenamic acid standard (NSAIDs) in surface water in Ho Chi Minh City is (IDQC, purity >99.9 %). Stock solutions of 1,000 necessary to provide a scientific foundation for future mg/L were prepared in methanol and stored at 4 0C. in-depth studies in thisdensely populated area. Working solutions were prepared by diluting the stock standard solutions in methanol. Solid phase 2. Materials and methods:
extraction system (Agilent) with vacuum pump and 2.1. Sampling:
Poly-Sery PSD (Poly styrene divinylbenzene) SPE Based on the monitoring points of surface water at tubes (250 mg, 6 mL) of DNW Technologies GmBh. Ho Chi Minh City [2], tidal levels [3] and weather LaChrom Hitachi HPLC system with Inspire C18 conditions, samples were taken at 15 locations (250 mm x 4.6 mm i.d., 5 m) column protected by spotted in Figure 1 within 3 surveys (September 23th an Inertsil ODS-3 (10 mm x 4.0 mm i.d., 5 m) guard 2013, October 21th 2013 and November 19th 2013). WCSET 2014164 BASHA RESEARCH CENTRE. All rights reserved. DO VU HOANG ANH, BUI QUANG MINH, PHAM HONG NHAT 2.2.2. Sample preparation:
500 mL samples were filtered through a 0.45 m MEC= measured environmental concentration cellulose acetate membrane filter to remove PEC= predicted environmental concentration suspended matters. The SPE cartridges were PNEC= predicted no effect concentration conditioned with 6 mL ethyl acetate, 6 mL methanol - RQ = 0.01 - 0.1: low risk and 6 mL ultrapure water. 500 mL samples were then - RQ = 0.1- 1.0: medium risk transferred to the SPE cartridges. The loaded - RQ > 1.0: high risk cartridges were rinsed with 3mL of methanol:water To anequitoxic mixture (a mixture where each (5:95, v/v) solution and 3 mL n-hexane. After the chemical contributes the same to toxicity): a sum risk enrichment step, the cartridges were vacuum dried. quotient (RQmix) is total of risk quotients of the The elution was performed with three 3-mL aliquots individual pharmaceuticals (RQi) of ethyl acetate. Extraction was done under vacuum at the flow rate of 3 mL/min. The effluent was dried under the stream of nitrogen. The residues were dissolved in 0.5mL methanol and injected into the PNEC values of ketoprofen, ibuprofen, diclofenac 2.2.3. Analysis:
sodium and mefenamic acid are 15.6 g/L, 5.0 g/L, After solid phaseextraction, samples were injected on 13.5 g/L and 0.428 g/L respectively [7, 8, 9, 10, HPLC-DAD system under a defined condition (Table Table 1.HPLC-DAD conditions.
2.3.2. Hazard Index (HI) [13]:
Health risk can be assessed by Hazard Index (HI) as follows: Injection volume Mobile phase (isocratic) CDI = chronic daily intake for the ith toxicant in mg/kg-day, and RfD = chronic reference dose for the ith toxicant in Oven temperature NOAEL= no-observed-adverse-effect level Ufinter = interspecies uncertainty factor Ufintra = intraspecies uncertainty factor, and Ufother = additional uncertainty factors Method detection limit (MDL), method quantitation limit (MQL) and recovery (H) are 3. Results and discussions
presented in Table 2. Based on calculated risk quotients (RQ) and total risk Table 2.MDL, MQL and recovery (H).
quotient (RQmix) of the four studied compounds, the Compounds
following findings are made: In the first survey, ketoprofen and diclofenac sodium were found at a low risk level for the studied surface water. Ibuprofen was also at a low risk level except for at Le Van Sy Bridge sampling site where it was of a high level. Especially, mefenamic acid wasat high risk levels in almost all sampling locations except for only Thu Thiem Bridge where it was at a medium risk level. Total risk quotient of ketoprofen, ibuprofen, diclofenac sodium and mefenamic acid 2.3. Determination of risk quotient (RQ) and
(RQmix) proved that 14 out of 15 sites were in a high hazard index (HI)
environmental risk level range whereas the Thu 2.3.1. Risk quotient (RQ) [6]:
Thiem Bridge site was of a medium level. Environmental risks of NSAIDs for surface water were determined via risk quotient (RQ), which was calculated by the equation: Proceedings of the 3rd World Conference on Applied Sciences, Engineering and Technology 27-29 September 2014, Kathmandu, Nepal, ISBN 13: 978-81-930222-0-7, pp 724-727

Environmental Risks of Some Non-steroidal Anti-inflammatory Drugs (NSAIDs) in Surface Water in Ho Chi Minh City Figure 2.RQs and RQmix at 15 sampling sites in the
Figure 4.RQs and RQmix at 15 sampling sites in the
first survey third survey Data from the second survey show the same trend as In summary, calculations from ketoprofen, ibuprofen, of the first survey. Ketoprofen and diclofenac sodium were also under a high risk range. Ibuprofen at Le concentrations in surface water in Ho Chi Minh City Van Sy Bridge was at a medium risk level whereas it in the three surveys indicates that the environmental was found at a high risk during the first survey. risk levels of the first three compounds were not high Mefenamic acid was identified at high risk levels for except for ibuprofen at Le Van Sy Bridge in the first almost all sampling sites except for Saigon Bridge and second surveys. Mefenamic acid consistently and Thu Thiem Bridge. Total risk of the four was of high risk levels at almost all sampling sites. compounds at Saigon Bridge and Thu Thiem Bridge Furthermore, total risk levels of the four studied was of a medium risk level while at the remaining 13 compounds in surface water in Ho Chi Minh City, sites of a high level. RQs during this survey slightly which were greatly affected by mefenamic acid risk decreased as compared to those at the first survey. levels, were at high levels in most cases. The question is if the surface water is suitable for human drinking and other daily domestic activities. To partly answer this question, hazard index (HI) has been assessed for the four studied compounds. HI values calculated from CDI and RfD for each individual as well as for all the four studied compounds were both smaller than unity. This means that at present no adverse health effect can be caused by the four studied NSAIDs. Therefore,the surface water can still be used as a safe source for drinking and other daily domestic activities. In the future, however, the presence of these compounds in the study surface water needs to be monitored. The four studied NSAIDs including ketoprofen, Figure 3.RQs and RQ
ibuprofen, diclofenac sodium and mefenamic acid are mix at 15 sampling sites in the second survey currently present in surface water in Ho Chi Minh In the third survey, the risk levels of ketoprofen, City at high environmental risk levels. Although the ibuprofen, and diclofenac sodium still could not be surface water is still safe for drinking and other daily rated as high. Similarly to the earlier surveys, all domestic activities, the studied compounds might mefenamic acid risk levels were at a high range have potential impacts on the aquatic ecosystem in except for at Khanh Hoi Bridge and Dien Bien Phu the future if their use consistently increases. Bridge. Although the total risk quotients of the four compounds (RQmix) were lower than those in the The authors acknowledge support from the laboratory second survey, they were still at high levels except of the Institute of Environmental Technology, within for at Khanh Hoi Bridge and Dien Bien Phu Bridge. the Vietnam Academy of Science and Technology. Special thanks are to Mr. Nguyen DuyLinh for taking part in the development of analysis method, Ms. Tran Minh Huong for revising the English and Ms. Tran Phuong Lien for editing the text. Proceedings of the 3rd World Conference on Applied Sciences, Engineering and Technology 27-29 September 2014, Kathmandu, Nepal, ISBN 13: 978-81-930222-0-7, pp 724-727 DO VU HOANG ANH, BUI QUANG MINH, PHAM HONG NHAT References:
Thomas Heberer, "Occurrence, fate, and B. Ferrari, R. Mons, B. Vollat, B. Fraysse, N. removal of pharmaceutical residues in the Paxeus, R.L. Giudice, A, Pollio and J. Garric, aquatic environment: A review of recent "Environmental risk assessment of six human research data", Toxicology Letters,131 1-2,5- pharmaceuticals: environmental risk assessment procedures MONRE, NEA, The Environmental sufficient for the protection of the aquatic Monitoring Network of Ho Chi Minh City, environment",Environmental Toxicology and 2009. Retrieved on January 8, 2014 at: Chemistry, 23 5,1344-1354,2004. [10] T.H. Fang, F.H. Nan, T.S. Chan and H.M. Feng,"The occurrence and distribution of pharmaceutical compounds in the effluents of a major sewage treatment plant in Northern Centre of Oceanography, Tide Table 2013, waters",Marine Pollution Bulletin, 64 7, Natural Science and Technology Publisher, 1435–1444, 2012. T. Kosjeket, E. Heath and A. Krbavcic, Alonso,"Occurrence and risk assessment of pharmaceutically inflammatory drug (NSAIDs) residues in wastewater treatment plants. A case study: water samples", Environment International, 31 Environment International, 33 4,596-601,2007. D.V.H. Anh, B.Q. Minh, N.D. Linh and P.H. A. Tauxe-Wuersch, L.F. De Alencastro, D. Nhat, "Determination of non-steroidal anti- Grandjean and J. Tarradellas,"Occurrence of inflammatory drugs (NSAIDs) in surface several acidic drugs in sewage treatment plants water at Ho Chi Minh City",Journal of in Switzerland and risk assessment",Water Science, Natural Sciences and Technology, 30, Research, 39 9,1761–1772,2005. [12] U.S. EPA Region 6,Human Health Risk B. I.Escher, R. Baumgartner, M. Koller, K. Assessment Protocol, Treyer, J. Lienert and C.S. McArdell, Characterizing Risk and Hazard, 2005. [13] Department of Health,Acute reference doses assessment of pharmaceuticals from hospital for agricultural and veterinary chemicals, wastewater", Water Research, 45 1, 75-92, Australian Goverment, Department of Health, Office of Chemical Safety, 2013. Stuer-Lauridsen, M. Birkved, L.P. Hansen, [14] The European Agency for the Evauation of H.C. Holten Lutzhoft and B. Halling- Medicinal Products, Diclofenac, 2003. Sorensen, "Environmental risk assessment of [15] Risk Profile Ibuprofen, 2012. Retrieved on human pharmaceuticals in Denmark after normal therapeutic use", Chemosphere, 40 O.A. Jones, N. Voulvoulis and J.N. Lester, "Aquatic environmental assessment of the top [16] Pfizer, Material Safety Data Sheet Mefenamic 25 English prescription pharmaceuticals", acid, 2007. Retrieved on January 9, 2014 at: Water Research, 36 20, 5013–5022,May 2002. Proceedings of the 3rd World Conference on Applied Sciences, Engineering and Technology 27-29 September 2014, Kathmandu, Nepal, ISBN 13: 978-81-930222-0-7, pp 724-727




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