УДК 502.31
YermakovychI., postgraduatestudent, Samoylenko N, PhD
National Technical University “Kharkiv Polytechnic Institute”, Kharkiv, Ukraine
WaterpollutioinbyPHARMACEUTICALSremainsANDtheirderivatives
Nowadays, pharmaceuticalsectorofindustryis one of the mostdevelopedindustrial areasnot only in Ukraine, but all over the world. Every day,more and more pharmaceutical substances and their derivatives are founded gettingin the household and industrial waste, sewage and soil. At the same time, the greatest danger is the presence of these compounds in the open ecosystemssurface waters. According to the results of theresearch[1,2], the remnants of drugs and their derivatives are found in surface waters in France, USA, UK, Germany, Denmark and Sweden. These substances alsoshow the presencein sewage sludge, river and ocean sediments and in the municipal landfills filtrates [1,2].
Sewages and rivers contain a wide range of pharmaceutical compounds and their metabolites, which can be classified into the following groups:
- antibiotics (almost all groups) and antimicrobial agents;
- antifungal agents;
- hormonal agents;
- anti-inflammatory and antipyretic agents;
- anti-depressants;
- lipid-loweringmedicines.
These groups of drugs belong to the most important and commonly prescribed worldwide pharmaceuticals, with an annual production of several kilotons. Their getting into the environment is a potential danger not only for the flora and fauna, but also for human in general [3].
Table 1 shows thedata ofthe presence of drugsresidues in the waters of Europe and the USA.
Table 1. Concentrations of pharmaceuticals in the natural waters
Medical class / Substance / Concentrations,10-6g/l / Calculated removal efficiency,% / References
Antibiotics / Ciprofloxacin / 0,03; 0,025 / [4, 9]
Norfloxacine / 0,12; 0,076 / [4, 9]
Sulfamethoxazole / 1,9; 0,14 / [4, 9]
Tetracycline / 0,11; / [9]
Analgesics and anti-inflammatory drugs / Diclofenac / 1,0; 0,81 / 17-69 / [4, 9]
Naproxen / 0,39; 0,074 / 66-93 / [4, 9]
Ibuprofen / 3,4; / 90 / [4]
Antiseptic / Triclosan / 0,15; 2,3 / 55-95 / [3, 4]
β-blockers / Bisoprolol / 2,9 / [4]
Metoprolol / 2,2 / 83 / [4]
The content of these drugs in the wastewater enteringthe municipal sewage treatment plantsisestimated tens or hundreds of times higher (Table 2).
All kinds of drugs have a negative impact on members of ecosystems, causing their relevant violations.Thus, hormonal medications, being one of the most widespread substances, can cause thechanges in the endocrine mechanisms in natural environment. For instance, the feminization of certain species of fish in the Great Lakes in the United Statescan be seen asfirst prerequisite of unintentional environmental contamination of medicines [4]. It is proved that the contraceptives and steroids may adversely affect the birth and development of fish, reptiles and aquatic invertebrates [5]. In accordance with data obtained by American scientists,12of the 62 substances identified in the rivers of IowaState, remain a small hormonal activity in surface waters[6].
Table 2. Concentrations of pharmaceuticals in wastewater enteringthe water treatment
Medical class / Substance / Concentrations,10-6g/l / Calculated removal efficiency,% / References
Antibiotics / Ciprofloxacin / 0,01; 0,16 / [9, 11]
Norfloxacine / 0,01; 0,23 / [9, 11]
Sulfamethoxazole / 0,02; 0,05;0,43 / [5,9,11]
Tetracycline / 0,02; 0,3 / [9, 11]
Analgesics and anti-inflammatory drugs / Diclofenac / 0,16; 5,45; 1,89 / 22 / [3, 5,9]
Naproxen / 3,65 0,92 / 93 / [5,9]
Ibuprofen / 3,59; 0,018 / 96 / [5,11]
Antiseptic / Triclosan / 0,38; 0,650 / 58 / [3, 5]
β-blockers / Metoprolol / 0,16; / 83 / [5]
Anti-epileptic / Carbamazepine / 1,68 0,011; 2,5 / 30 / [3, 6,11]
Almost all groups of antibioticsare definedin the studied waters. Likeanti-microbial agents, theyshow a strong toxic effect of many infectious organisms of humans and animals, including bacteria, fungi and parasites. However, thisfact does not mean that their influence is limitedby these effects. Many lower animals may become a target for drugs, so-called non-target organisms, which play an important role in the functioning of ecosystems. Adverse effects of the influence of drugs and their derivatives have been studied and shown on the physiological interaction between theinsects and their behavior, inhibition or stimulation of growth of aquatic plants and algae [4].
Many studiesof the life cycle of insects have shown that carbamazepine (antiepileptic drug) affects the reproduction of midges (gnats-Zvontsov), water mosquitoes in natural waters [4]. The active substance of the drug carbamazepine benzo [b] [1] benzazepin-11-carboxamide ismostly found in sewage and surface waters due to the low rate of biodegradation [3]. Studies performed on the effect of carbamazepine on bacteria, algae, invertebrates and fish, identified itas a highly negative component for the water objects where both diclofenac and clofibric acid are found in water [3]. This acid cannot be destroyed in the environment more than 21 years [3].
In the last decades,anincrease ofpharmaceutical substances containing fluorine is also widely observed. These substances shownot only better bioavailability in the human body, but also significant persistence in the environment [2].
The results ofstudies within the European Program for ecological risk assessment (ERA) of pharmaceuticals showed that 15% of them were stable in water and 50% - in the sediment (evaluation of the stability criterion in accordance with the EU-TGD). It is proved that,besides thehormones and antibiotics, the psychotropic and analgesic agents also pose anenvironmental risk. Thus, the antidepressant fluoxetine and ibuprofen analgesics also present a danger for the environment [2, 17].
Recent monitoring carried out in the United States, showed that some drugs may themselves highlight no toxic effects on aquatic flora and fauna. However, eitherseveral pharmaceutical products or their derivatives may have interactive effects such as additive compounds with similar mechanisms of action and synergy [2]. For example, the antibiotic lincomycin shows these properties in combination with 27 additional chemical substances [1].
Main causeofdrugs and their derivatives gettingin surface waters is the lack of an effective biological purificationof sewage treatment plants, from hospitals, clinics, pharmaceutical companies, sick population, and also imperfect destruction of substandard medicines with pharmaceutical form of solutions and syrup (diluted with water in a ratio of1:200 and gradually discharged into the sewer).
Activated sludge from sewage treatment plants, representing a complex community of microorganisms of different taxonomic groups and multicellular animals, do not fully decompose some of the "biologically stable" drugs. Consequently, the small doses of pharmaceutical substance partially remain in the activated sludge, and then get into surface water, soil and accumulate there [12].
The microconcentrations effect of the antibioticsgroups such as tetracyclines, aminoglycosides, sulfonamides on activated sludge is thereductionofthe nitrification process and dehydrogenase activity[7, 8, 16]. The low value of the last one indicates the withering away and auto-oxidation of the majority microorganisms of activated sludge. This respectively leads to a lack of sewage treatment plant in general, when they are discharged into thesurface waters. According to[7], some chemicals rest toxic during the process of sewage treatment and arenot amenable to biodegradation. Thesesubstancesinclude, for example, sulfonamides, which are widely used in the treatment of humans and animals. They show toxicity to nitrifying bacteria, a weak adsorption in soil, and their migration into the environment can lead to contamination of drinking water and food [13].
Thus, the removal of pharmaceuticals during sewage treatment, even in modern wastewater treatment plants is not enough, and conditionally pure waters still contain one or another their quantity[13].
The statistical organization of the Swedish pharmaceutical company Apoteksbolaget presented data on the quantity of drugs sold in the region of Scania (1145000 people), where Lundcityis the second largest. A rough theoretical estimation of the influence of pharmaceutical products and their derivatives on theurban wastewater treatment plants was performed onbase on the rate of drug consumption per capita (of Scania) multiplied by the population in Lund (79 000) in combination with quantitativedata of drugs that are derived from the human organism [5].
The results of these calculationsare presented in Table 3.
It is worth to be mentioned concentrations of gemfibrozil, trimetoprim and atenololmeasured experimentally are much lower in comparison with estimated, whiletheconcentrations of carbamazepinesubstantially exceed values determined theoretically. The measured and theoretical concentrations for diclofenac, naproxen and metoprolol areclosed to each other [5].
Table 3. Comparison of theoretical and measured concentrations of drugs in municipal wastewater
Medical class / Substance / Theoretical concentrations,10-3g/l / Measured concentratios,
10-3g/l / References
Anti-epileptic / Carbamazepine / 0,11 / 1,68 / [5]
Antimicrobial / Metronidazole / 0,1 / 0,01 / [6]
Antibiotics / Ofloxacin / 0,5 / 0,05 / [6]
Ciprofloxacin / 0,6 / 0,06 / [6]
Analgesics and anti-inflammatory drugs / Diclofenac / 0,32 / 0,16 / [5]
Naproxen / 5,72 / 3,65 / [5]
Ibuprofen / 0,46-3,66 / 3,59 / [5]
Antimicrobial / Trimetoprim / 0,37 / 0,00008 / [5]
β-blockers / Atenolol / 3,38 / 0,03 / [5]
Propanolol / 0,01 / 0,05 / [5]
Metoprolol / 0,18-0,59 / 0,16 / [5]
Lipid-lowering drugs / Gemfibrozil / 3,25 / 0,71 / [5]
By mischance,theresearch on water pollution pharmaceutical products and their derivatives has been not performed in Ukraine. The authors of this paper attempt to estimate the possible concentration of the cyclic compound-baseddrug in the wastewater entering the municipal wastewater treatment plant in Kharkivand the conditions allowing toassignitto "biologically hard compounds". "Metronidazole"substance has been chosen with this aim. Its active ingredient (1 - (b-hydroxyethyl)-2-methyl-5-nitroimidazole) is antiprotozoal and antimicrobial agent. This medicament is often prescribed to patients as anassociated with antibiotics during the treatment and is included in the listofvitally essential medicines.
The calculations took into account the following factors:
- population of the city (1452300 people);
- the number of medical institutions (hospitals, clinics, maternities) and their patients;
- weight of the drug, which is excreted by the kidneys in unchanged form (20%);
- seasonal periodicity of diseases in which the drug may be appointed (factor 1.1-1.3);
- epidemic disease, contributing to additional prescribing of the drug topopulation (ratio 1.1-1.7);
- the capacity of sewage treatment plants - 700 000 m3 per day.
The calculation results showed that, depending on the season and the epidemiological situation in the city, the concentration of metronidazole enteringthe wastewater treatment plant, is between 0.00298 mg/m3 and0.0506 mg/m3 perday. Accountingthe lack of effective purificationfor these effluents of this drug is continuously growing in surface waters.
Conclusions: Studies in the laboratories of the USA and Europe show that the contaminantsof almost all groups of pharmaceuticalshave been foundin natural, waste water and drinking water, and the interaction mechanism of these substances is not clearlyunderstood. A lot ofdatabases with the information about control, location detection and possible effects of pharmaceuticals microquantities on the environment and biota are created in these regions.
Unfortunately, such studies are not supported in Ukraine, and today the real extent of contamination of aquatic environments of pharmaceuticals and their derivatives are not widely known.In the current situation, primaryproblems in the protection of water objects are:
-toconduct the monitoring of the surface water quality and supply the management services by the information about changes,the water quality;
-to improve an efficiencyof wastewater treatment plants;
- to perform a local treatment of sewagecontaining biologicallydifficult degradable compounds in the places of their maximum accumulation.
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