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A review on pollution situation and treatment methods of tetracycline in groundwaterIntroduction
In recent years, the use of drugs has increased yearly, and the situation of drug abuse has become more serious, which caused the drug remained in the environment. Meanwhile, the residual drug in the environment was relatively stable and difficult to handle by conventional methods. Among the numerous drugs which existed in the environment, antibiotics were widely used in the world.
In the past few decades, the use of drugs was growing rapidly. Tetracycline antibiotics (TCs) were the most common antibiotics all over the world. TCs are a family of broad-spectrum antibiotics produced or semi-synthesized by actinomycetes and they are effective against to Gram-positive and Gram-negative bacteria as well as against a variety of bacterial infections. TCs are a class of tetrahydrobenzene derivatives with a dibasic tetraphenyl base structure. TCs mainly contain TC, oxytetracycline and chlortetracycline. The overall structure of oxytetracycline was found by Woodward et al. (1947) by chemical degradation and infrared spectroscopy.[1] Chlortetracycline is isolated from the culture medium of Streptomyces spp. TC is obtained by getting rid of the chlorine atom of the chlortetracycline.[2] TC plays an important role in TCs, it’s also the largest proportion of in TCs. TC also has many advantages, such as, low prices, high quality. TC has also many advantages such as low production prices and could be synthesized with great purity. However, TC is difficult to be absorbed by animal metabolism, most of which is in the form of maternal compounds discharged into the environment by the excrement. It can be residual in the water for a long-term.[3] The amount of TC in most countries of the world has no clear rules. The uncontrolled usage of TC and its arbitrary released into the environment pose a certain threat to the ecological environment. TC affects the development of teeth, bones and also has certain hepatotoxicity. The researcher found that high levels of fecal waste might bring huge pollution problems once they came into groundwater.[4] TC excreted by human and animal enters the water environment. It could cause water pollution, after infiltration, leaching, and other processes. The contents of TC in surface water and groundwater were more than 100.00 ng/L in the wet season in Hanjiang plain.[4]
Research of TC pollution to groundwater and its treatment technology are great significance to human health. TC was detected at a concentration of 184.2 ng/L in shallow groundwater in china.[5] Although TC is not easy to cause acute toxicity in normal circumstances, long-term exposure to TC in water environment may be the potential for chronic toxicity to non-target organisms.[3] In order to solve the residual TC, researchers used variety methods to deal with TCs in groundwater.[6] Most removal methods of TC could not directly remove groundwater pollution. Generally, TC is removed indirectly by wastewater, and the methods also applied to drinking water. There were various methods of TC removal in water environment, and their degradation efficiency was different. This article described the commonly used TC removal methods included, photodegradation, microbial degradation, phytodegradation, adsorption processes and electrochemical processes.[7] The new methods of TC degradation include sludge digestion technology, membrane processes, advanced oxidation processes, hydrolysis process, ultrasonic degradation, low-temperature plasma technology and soil infiltration system.[8] This article indicated the status, amount, source, toxicity, and removal methods of TC in groundwater. It would provide a reference for the property and treatment of TC in groundwater.
Physicochemical properties of TC
TC is mainly synthetized as an odorless yellow crystalline powder. TC is slightly soluble in water, lower in alcohols (methanol, ethanol, etc.), and insoluble in organic solvents.[9] TC is dissolved in dilute acid and dilute alkali. TC antibiotic is stable in the air, but it is easy to absorb moisture. The case of sunlight can change the color of TC. The efficacy of TC will be significantly reduced or even produce toxicity. TCs have similar physicochemical properties, such as the similar chemical structure and molecular weight. The differences among TCs are the groups of R1 and R3, which are shown on Table 1. The main physical and chemical properties of TCs are shown in Fig. 1. TC mainly consists with four carbocycles, which contains dimethylamino group (N(CH3)2), acylamino group (CONH2), phenolic hydroxyl group (C-OH), a ketone group (C = O) and an enol group conjugate double bond system at the same time. TC is a kind of quaternary weak acid, there are four kinds of forms in aqueous solution. When the pH is less than 3.3, the dimethylamino group in the TC molecular structure is protonated, mainly in the presence of cation TCH3+. When the pH value is 3.3–7.7, the TC molecules in the phenolic ketone group lost protons, with zwitterions TCH2±. When the pH value is more than 7.7, the TC molecules is in the form of anion TCH2− or the divalent anion TC2-.[12,13] The different forms of TC according to pH are shown in Fig. 2.
Table 1. The molecular weight and molecular formula of tetracycline antibiotics.
CSVDisplay Table
Figure 1. The structural formula of tetracycline.
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Figure 2. The presence of TC in different pH conditions.
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The source and pollution conditions of TC
The amount of TC was not clearly defined in the initial. Therefore, the abuse of TC has emerged in the world. China’s total antibiotic production reached 21000 tons in 2009, accounts for about half the world’s consumption.[14,15] Because of the broad spectrum of antibacterial and stable naphthalene ball structure, TC was difficult to degrade.[16] A small fraction of TC came into the body to produce inactive products through metabolic reactions such as cleavage and glucuronidation.[17] The antibiotic metabolites that excreted from the body were still biologically active, and they could form a matrix in the environment and even produce more degraded substances than pre-degraded.[18,19] About 69–86% of the TC antibiotics were excreted through the urine and feces of the human body and animals, then they were released into the environment in an active form.[18] TC has a high degree of hydrophilicity and low volatility, with significant persistence in water environment. The inappropriate use of TC poses a threat to human health and ecological security. TC carried in the feces contacts the soil and further enters the surface water. In the long run, TC in surface water penetrates into groundwater. At present, the control of the groundwater environment is still not perfect. TC entering the groundwater is difficult to detect. It is difficult to identify the pollutants and sources when groundwater is contaminated. Therefore, it is imperative to study the source of TC and its pollution in groundwater.[20]
The source, the use, and the pollution situation of TC
The source of TC contamination is mainly from human and veterinary drugs. The main source of TC contamination is shown in Fig. 3. As for human drugs, TC enters into human body through the way of injection and oral consumption. However, due to the lack of restraint mechanisms, antibiotics were used without abstinence. The antibiotics were discharged randomly, and made the adverse effect. There are three main sources of antibiotic pollution. The first source is the unused expired antibiotic used from the medical institution. Secondly, medical institutions have left antibiotics in discarded medical devices. Thirdly, the excrement of patient’s also carries raw antibiotics and metabolized antibiotics.[21] These unused antibiotics discharge into the environment through the urban sewage system. On the one hand, the antibiotics in treated wastewaters infiltrate in soils and surface waters, and enters into the groundwater indirectly. On the other hand, they enter the urban sewage treatment system. The existing sewage treatment technology can not completely remove the antibiotics. The biochemical treatment of wastewater in the microbial growth has a strong inhibitory effect, so the antibiotics are difficult to degradation.[22,23] Once the antibiotic into the surface water, they will cause pollution of the water environment.
Figure 3. The migration of antibiotics in water environment.
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As for veterinary drugs, TC is often used as feed additives into animal. The use of antibiotics in animal husbandry and aquaculture are the two main sources of veterinary antibiotics. These antibiotics will also be into the water environment in the form of the animal excretion. According to the statistics, most of livestock and aquaculture exist in rural areas. Sewage treatment system is lacked in rural areas, so the fecal matter goes directly into surface water. TC issued from veterinary drugs does not reach directly groundwater. On the one hand, wastewaters containing TC are discharged in surface waters. Then, TC migrates to hyporheic zone and finally reaches groundwater. On the other hand, wastewaters can be discharged on soils and then they penetrate in the non-saturated zone. In consequence, TC infiltrates through the vadose zone before to reach groundwater.
In 1950s, the US Food and Drug Administration (UFA) formally approved the application of TC antibiotics to animal feed additives at first.[16] Because of the broad-spectrum and low prices, TCs has been widely promoted in the animal husbandry.[24,25] Statistically, the European Union annual production of antibiotics is about 5,000 tons, accounting for 46–50% of the total antibiotics.[9] Britain produces 438 tons of antibiotics each year, the production of TCs is 228 tons, accounting for 52% of the total antibiotics.[9] As for China, the production of TCs is about 97,000 tons, accounting for 46% of the total antibiotics.[9]
Antibiotics have created enormous economic benefits in human health and the development of animal husbandry.[26] TCs are widely used in veterinary drugs and treated for gastrointestinal tract, respiratory tract, skin infections, and sepsis and other diseases.[27,28] Taking TC veterinary drugs as an example, the total amount of TC antibiotics around the world is shown in Fig. 4. In recent years, people have found some new uses of TC antibiotics, especially non-antibacterial effects.[29] TC treatment of type Ⅲ prostatitis infected by Nanobacteria.[30] Injection of TC hydrochloride as a hardening agent, adjuvant treatment of malignant pleural effusion, treatment of liver and kidney cysts and other diseases.[31] TC and minocycline can be used as anti-osteoporosis drug.[32] Dr. Maria Amy (a medical researcher in New York State University) reports that Periostat (doxycycline monohydrate) is effective in the treatment of chronic gingivitis.[33]
Figure 4. The total amounts (tons) of TCs used for veterinary purposes around the world.
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The water pollution by antibiotics is a combination of point source and surface source emissions.[34] Because antibiotics are hydrophilic and low volatility, their main migration in the environment is through water and food transfer.[35,36] For instance, in China, most of groundwater pollution problems exist in the livestock and poultry breeding and aquaculture of rural China. There are several common problems, for example, the selection of farm site is not standardized, animal feces, and sewage discharge is not up to standard pollution prevention and control. The average content of residual TC in pigs is 9.09 mg/kg.[37] The Ministry of Agriculture of the People’s Republic of China indicated that China’s annual livestock and poultry manure production is about 3.80 billion tons in 2016, however, the comprehensive utilization rate is less than 60%.[38] High levels of fecal waste might bring huge pollution problems once they come into the groundwater. These problems are superimposed on causing serious damage to TC antibiotics in surface water and groundwater of rural areas.[39]
At present, most countries and regions of the groundwater TC antibiotic pollution have not been systematically detected. And the literature of detection is very little. The researchers in Beijing Normal University, (2015) had a test to part of the surface water sampling in China.[40] They found that antibiotic content is amazing. The detection results of 19 kinds of sulfonamides, fluoroquinolones, TC, and macrolide in the Jianghan Plain in the surface water and groundwater in the dry season and the wet season shows that, the maximum concentrations of chlortetracycline in surface water and groundwater are 122.30 and 86.60 ng/L, respectively.[41] The contents of TC, ofloxacin, norfloxacin, and erythromycin in surface water and groundwater are more than 100.00, 135.10, 134.20, and 381.50ng/L, respectively.[41]
Toxicity
Effects of TC on aquatic animals in water environment
TC is difficult to cause acute toxicity, however, the long-term exposure to antibiotic in the environment may be the potential for chronic toxicity to non-target organisms. The widely use of TCs has caused the effect of micro-organisms in the terrestrial environment and plant growth.[42] The bacteria in natural environments can transmit antibiotic-resistant genes, which has the potentially threatens in ecosystem and human health.[43] on the other hand, the antibiotic resistance gene is found in the environment and it was characterized as a new type of contaminant. Zhu et al. (2017) published an essay in Science.[44] This article described the antibiotics as a pollutant during the water and soil microbial migration process. In order to resist antibiotics and other pollutants “threat”, the microbes had to occur gene mutation or gene lateral transfer. They gradually produce “resistance” to take the initiative to respond to a changing environment.[45] Therefore, the global antibiotic resistance problem has reached an urgent point.
Wollen-berger et al. (2000) conducted acute and chronic toxicity tests on freshwater crustacean large fleas in fisheries according to the standard protocol (ISO, 1989b) of the flea acute toxicity test.[46] This experiment used 9 kinds of antibiotics including TC antibiotics. The results showed that TC NOEC50 (No observed effect concentrations) was 340 mg/L (the highest effective concentration for parent animals and propagation was considered as NOEC). In acute toxicity experiments, the antibiotics had a mass concentration that affected the reproductive performance of large fleas, several times lower than the acute toxicity concentration. In the chronic toxicity test, the EC50 (concentration for 50% of maximal effect) of TC was 44.80 mg/L and the EC50 of oxytetracycline was 46.20 mg/L.[46]
Ferreira et al. (2007) conducted a toxicity test on the use of microalgae Tetraselmis chuii and the crustacean Artemia parthenogenetica.[47] TC can cause toxic effects on aquatic organisms. The results showed that IC50 (half maximal inhibitory concentration) of TC at 24 and 48h were 870.47 mg/L (95% confidence interval: 778.83–983.66 mg/L) and 805.99 mg/L (95% confidence interval: 650.71–1129.00 mg/L), respectively. And the NOEC and lowest observed effect concentration values were 637 and 828 mg/L, respectively.[47]
The research results above are mostly based on acute toxicity experiments, and they cannot fully feedback TC antibiotics toxicity. In recent years, due to the impact of experimental costs and ethics, the researchers use alternative research methods for acute toxicity test. Researchers try to reduce the use of larger animals such as fish and shellfish.[48] This is a method of innovation in TC antibiotics for aquatic animals. Sanderson et al. (2003) used quantitative structural relationships and compared the lowest predicted concentration to the highest detection concentration with obtain the ecotoxicity data of the contaminants.[49] The risk factor of a series of antibiotics (the ratio of the detected concentration of the predicted toxicity) can be obtained in this way. For example, the risk factor of TC was 6.88 × 10−6, and the risk coefficient of oxytetracycline was 2.13 × 10−5. The European Commission has proposed using the risk factor to evaluate the potential environmental risk of a drug by responding to the ratio of predicted environmental concentration to predict no-effect concentration. When the ratio is bigger than 1, it indicates a high risk.