The Connection Between Nitrate and Nitrite in Drinking Water and Human Health
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Introduction to nitrate and nitrite in drinking water
Nitrate and nitrite are two chemical substances in most tap water. They can be derived from agricultural run-off, sewerage, and even manufacturing. Nitrate and nitrite aren’t harmful at low concentrations, but concentrations in drinking water that reach dangerous levels are damaging to human health. Here we will explain in detail about nitrate and nitrite, their sources, prevalence and health effects in this paper.
The most important sources of nitrate and nitrite in the water are croplands and sewers. Nitrate is part of fertilisers and, when fertilisers are applied to the crops, they will dissipate into nearby groundwater or surface water [1]. Nitrite is the result of organic matter decomposition – sewage, for example [2].
Industrial processes can cause nitrate and nitrite levels in drinking water, too. For instance, some industrial activities may emit nitrate and nitrite as wastes which may then end up in the water source via discharge or leak [3].
The world is awash in nitrate and nitrite. Nitrate concentrations in drinking water are usually higher in the countryside where agriculture is common in the US [4]. Nitrite in drinking water tends to be highest in metropolitan areas where sewage is more common [5].
In water supplies at low concentrations, nitrate and nitrite are not usually thought of as pathogenic. But too much of them has health-altering effects.
One of the worst health effects of nitrate and nitrite in drinking water is methemoglobinemia ("blue baby syndrome") which is when nitrate levels are excessive in the bloodstream and prevent red blood cells from transporting oxygen [6]. The methemoglobinemia symptoms are cyanosis (bluish skin or lips), chest pain, and dizziness. The babies are especially vulnerable to methemoglobinemia because their bodies don’t use nitrate as well as they do as adults [7].
We also have data to show that chronic nitrate and nitrite contamination of drinking water can be linked to a greater incidence of certain cancers, particularly stomach cancer [8]. But much more needs to be done to know how well the connection between nitrate and nitrite in water and cancer is actually working.
Nitrate and nitrite are two chemicals that we normally encounter in drinking water. These chemicals can be a product of agricultural runoff, sewage and industry. Nitrate and nitrite are not considered toxic at small doses, but excessive levels in water can have detrimental effects on human health, from the development of methemoglobinemia to risk of certain cancers.
[1] "Nitrate and Nitrite in Drinking Water." World Health Organization,
[2] "Nitrate and Nitrite in Drinking Water." United States Environmental Protection Agency,
[3] "Nitrate in Drinking Water." Centers for Disease Control and Prevention,
[4] "Nitrate in Groundwater." United States Geological Survey,
[5] "Nitrite in Drinking Water." United States Environmental Protection Agency,
[6] "Methemoglobinemia." World Health Organization,
[7] "Blue Baby Syndrome." American Academy of Pediatrics,
[8] "Nitrate and Nitrite in Drinking Water and the Risk of Cancer." International Journal of Environmental Research and Public Health, www.mdpi.com/
Nitrate and nitrite levels in drinking water
Nitrate and nitrite are natural elements that are commonly found in the water we drink. Nitrate (NO3-) is nitrogen, which is easily absorbed by plants, and is a common fertilizer. Nitrite (NO2-) is the byproduct of nitrate reduction and is also in drinking water.
Nitrate and nitrite are both levels that the Environmental Protection Agency (EPA) is responsible for monitoring in drinking water, under the Safe Drinking Water Act (SDWA). The EPA has defined a 10 mg/L (ppm) maximum contaminant level (MCL) for nitrate and 1 mg/L (ppm) for nitrite [1]. These MCLs are derived from the health risks incurred from long-term use of high levels of nitrate and nitrite.
But these MCLs are derived from concentrations of nitrate and do not account for other chemicals, including bacteria, that could also be in the water we drink. In addition, the MCLs for nitrate and nitrite fail to consider health hazards of acute exposure to high concentrations of both chemicals [2].
Nitrate and nitrite in the water can be harmful to human health in several ways. : Overexposure to nitrate causes methemoglobinemia or "blue baby syndrome" in infants. This is the result of the hemoglobin conversion to methemoglobin which cannot deliver oxygen efficiently. It may cause cyanosis (bluish skin colour), palpitations and in severe cases, death [3].
Furthermore, Nitrate and Nitrite can also act as a carcinogen, according to the International Agency for Research on Cancer (IARC), nitrate and nitrite is possibly human carcinogenic (Group 2B) due to the limited evidence in humans and the ample evidence in experimental animals [4].
Along with their health risks, high nitrate and nitrite concentrations in water can be harmful to the environment. Nitrate and nitrite can lead to eutrophication – an excessive growth of algae and other plants by a surplus of nutrients [5].
Bottom line: Nitrate and nitrite are naturally occurring elements commonly found in drinking water, but they should be kept at a controlled level in order not to impact human health and the environment. You have to regularly test and monitor nitrate and nitrite levels in drinking water to make sure they’re within the EPA’s MCLs.
[1] Environmental Protection Agency. (2021). Safe Drinking Water Act.
[2] Environmental Protection Agency. (2021). Maximum Contaminant Level Goals and National Primary Drinking Water Regulations.
[3] Centers for Disease Control and Prevention. (2021). Methemoglobinemia.
[4] International Agency for Research on Cancer (IARC) (2021) Nitrate and Nitrite.
[5] United States Geological Survey (USGS) (2021) Nitrate and Nitrite in Groundwater.
Health effects of nitrate and nitrite
Nitrate and nitrite are naturally occurring chemicals common in well water. Such chemicals can be adverse to human health, especially when they’re in large quantities. In this subtopic, we’ll cover possible health consequences of high levels of nitrate and nitrite in drinking water for babies and pregnant women.
The most famous health effect of nitrate and nitrite is methemoglobinemia (also known as "blue baby syndrome") that arises when hemoglobin is converted to methemoglobin that can no longer carry oxygen. A lot of nitrate in water can result in infants with methemoglobinemia, resulting in cyanosis (blue skin tone), shortness of breath and even death [1].
nitrate and nitrite in water also expose pregnant women. Nitrate and nitrite can be turned into nitrosamines in the stomach, which are carcinogens [2]. Moreover, pregnant women with high levels of nitrate in drinking water have a higher probability of birth defects, including neural tube defects and cleft palate [3].
Furthermore, Nitrate and Nitrite can be cancer causing agent, International Agency for Research on Cancer (IARC) has declared nitrate and nitrite as human carcinogenic (Group 2B) according to inadequate evidence in humans and adequate evidence in lab animals [4].
The health of the population at large can also suffer when nitrate and nitrite in drinking water are too high. Nitrate and nitrite are linked to increased risk of certain cancers such as stomach cancer [5]. And nitrates in drinking water have been associated with thyroid disease and diabetes [6].
And the health effects of nitrate and nitrite in water do not apply just to newborns and pregnant women, but can affect anyone who consumes it. So it’s important to test and monitor nitrate and nitrite in your water as needed to stay within the safe ranges set by the Environmental Protection Agency (EPA) under the Safe Drinking Water Act (SDWA).
Final thoughts: Nitrate and nitrite are natural elements that you usually encounter in drinking water but, when they are present in high concentrations, they have various toxic effects on human health. Little children and pregnant women suffer from methemoglobinemia and birth defects in particular. The nitrate and nitrite levels in water must be controlled to ensure the safety of consumers.
[1] Centers for Disease Control and Prevention. (2021). Methemoglobinemia.
[2] World Health Organization. (2021). Nitrate and Nitrite in Drinking Water.
[3] National Institutes of Health. (2021). Nitrate and Nitrite in Drinking Water.
[4] International Agency for Research on Cancer (IARC) (2021) Nitrate and Nitrite.
[5] Environmental Protection Agency. (2021). Nitrate and Nitrite in Drinking Water.
[6] American Thyroid Association. (2021). Nitrate and Nitrite in Drinking Water.
Nitrate and nitrite metabolism in the body
Nitrate and nitrite are natural substances found in water supplies. They are usually taken in and then broken down by the body and their metabolism is vital to its potential effects. We will be discussing in this subtopic the process of metabolizing nitrate and nitrite within the body via enzymes, nitrogen oxides, etc.
: When we consume nitrate, nitrate is first converted into nitrite by nitrate reductase, an enzyme found in the mouth [1]. Nitrite then gets absorbed into the bloodstream and goes to other tissues. Nitric oxide (NO) is converted into nitrite by the enzyme nitric oxide synthase (NOS) in the stomach [2]. Nitric oxide is a signalling molecule that has many physiological functions including blood flow and blood pressure.
But Nitrate can also be broken down to Nitrite and Nitric oxide in the gut by normal gut microorganisms, Nitrite can then be broken down into Nitric oxide or Nitrogen dioxide, Nitrogen dioxide can be broken down into Nitric oxide in the blood. The nitric oxide generated in the stomach can be a shield against gastric damage and cancer [3].
Nitrite can also combine with secondary amines and amides to make Nitrosamines, which are carcinogenic [4]. This means nitrite should be minimised, especially in processed meats and other foods that can be high in secondary amines and amides.
Not only are nitrate and nitrite metabolic compounds potentially hazardous to health, but they can be harmful to the environment as well. Nitrate and nitrite also cause eutrophication, which is the overproduction of algae and other aquatic plants by nutrients in abundance [5].
In sum, if anything Nitrate/ Nitrite metabolism is important for its health benefits. Nitrate is first turned into nitrite by the enzyme nitrate reductase in the mouth, and then nitrite becomes nitric oxide by the enzyme nitric oxide synthase in the stomach. Nitric oxide is an endocrine gas that has a protective effect on gastric damage and cancer. But nitrite also reacts with secondary amines and amides to create nitrosamines, known carcinogens. So the consumption of nitrite needs to be limited, and processed meats and other foods that may be high in secondary amines and amides should be avoided. Then there is nitrate and nitrite, which lead to eutrophication, the overgrowth of algae and other aquatic plants by the presence of enough nutrients. Monitoring and controlling nitrate and nitrite in drinking water and food is a matter of public health and environment protection.
[1] Bode, P., & Bode, J. C. (2018). Nitrate and Nitrite in Human Health and Disease. Antioxidants & redox signaling, 28(6), 871-888.
[2] Palmer, R. M., Ferrige, A. G., & Moncada, S. (1987). Nitric oxide release accounts for the biological activity of endothelium-derived relaxing factor. Nature, 327(6122), 524-526.
[3] Liu, Y., & Kevil, C. G. (2019). Nitric oxide and gut health. Nitric oxide, 91, 1-10.
[4] World Health Organization. (2021). Nitrate and Nitrite in Drinking Water.
[5] Environmental Protection Agency. (2021). Nitrate and Nitrite in Drinking Water.
Nitrate and nitrite as carcinogens
Nitrate and nitrite are natural elements in the water and food supplies. These are compounds that have been the focus of intense studies, since they have been associated with cancer. In this section, we will look at the evidence of nitrate and nitrite as causes of cancer, as well as cancer type and mechanisms.
The International Agency for Research on Cancer (IARC) has designated nitrate and nitrite possibly human carcinogenic (Group 2B) due to inadequate evidence in humans and adequate evidence in experimental animals [1]. The main way nitrate and nitrite can behave as carcinogens is by being converted into nitrosamines in the stomach. Nitrosamines are carcinogens that have been linked to a risk of many cancers, including stomach cancer [2].
Processing meats (bacon, sausage) are a main intake of nitrate and nitrite [3] which are present in abundance in the diet. Studies have shown that eating a lot of processed meat has a higher risk of colon cancer [4]. Also, nitrate and nitrite found in drinking water were related to stomach cancer and esophageal cancer [5].
Nitrite can also react with secondary amines and amides to produce Nitrosamines which are carcinogens [6]. Therefore, we should not consume too much nitrite, particularly processed meats and foods that might contain lots of secondary amines and amides.
And not only that, nitrate and nitrite are also found to collaborate with other carcinogens in the body, including polycyclic aromatic hydrocarbons (PAHs), to drive cancer risk [7]. Nitrate and nitrite also change the hormone metabolism of the body including oestrogen and hence can cause cancer [8].
All of this to conclude that nitrate and nitrite could be carcinogens – at least in the stomach, where they can be converted into nitrosamines. There is evidence that consumption of processed meats, nitrate and nitrite in the water we drink are all associated with risk of certain cancers. Limit your consumption of nitrite — particularly processed meats and other foods that are likely high in secondary amines and amides. Then there’s the monitoring and control of nitrate and nitrite in drinking water and food to keep everyone healthy.
[1] International Agency for Research on Cancer (IARC) (2021) Nitrate and Nitrite.
[2] World Health Organization. (2021). Nitrate and Nitrite in Drinking Water.
[3] World Cancer Research Fund/American Institute for Cancer Research. (2018). Processed Meat and Cancer.
[4] Aune, D., Norat, T., Romundstad, P., & Vatten, L. J. (2013). Meat consumption and the risk of colorectal cancer: a systematic review and meta-analysis of cohort studies. Annals of Oncology, 24(6), 1417-1429.
[5] World Health Organization. (2021). Nitrate and Nitrite in Drinking Water.
[6] World Health Organization. (2021). Nitrate and Nitrite in Drinking Water.
[7] World Health Organization. (2021). Nitrate and Nitrite in Drinking Water.
[8] World Health Organization. (2021). Nitrate and Nitrite in Drinking Water.
Nitrate and nitrite as cardiovascular risk factors
Nitrate and nitrite are naturally occurring compounds that can be found in drinking water sources and food products. These compounds have been the subject of much research due to their potential role as cardiovascular risk factors. This subtopic will investigate the potential role of nitrate and nitrite in cardiovascular disease, including hypertension and stroke.
One of the main mechanisms by which nitrate and nitrite may increase the risk of cardiovascular disease is through their conversion to nitric oxide (NO) in the body. Nitric oxide is a signaling molecule that plays a role in the regulation of blood flow and blood pressure [1]. However, when nitrate and nitrite are converted to nitric oxide in excessive amounts, it can lead to an increase in blood pressure and hypertension [2].
High levels of nitrate and nitrite in drinking water have also been associated with an increased risk of stroke [3]. A study conducted in China found that individuals who consumed water with high levels of nitrate had a significantly increased risk of stroke compared to those who consumed water with lower levels of nitrate [4].
Additionally, Nitrate and Nitrite can react with secondary amines and amides to form Nitrosamines which are known carcinogens [5], Nitrosamines have also been associated with an increased risk of cardiovascular disease [6].
Furthermore, nitrate and nitrite can interact with other cardiovascular risk factors, such as high cholesterol and diabetes, to increase the risk of cardiovascular disease [7]. The mechanisms by which nitrate and nitrite may increase the risk of cardiovascular disease are complex and not fully understood.
In conclusion, there is evidence to suggest that nitrate and nitrite may increase the risk of cardiovascular disease, including hypertension and stroke. High levels of nitrate and nitrite in drinking water have been associated with an increased risk of stroke, and their conversion to nitric oxide in excessive amounts can lead to an increase in blood pressure and hypertension. Additionally, Nitrate and Nitrite can react with secondary amines and amides to form Nitrosamines which are known carcinogens and also have been associated with an increased risk of cardiovascular disease. It is important to monitor and regulate nitrate and nitrite levels in drinking water and food to protect public health.
[1] Bode, P., & Bode, J. C. (2018). Nitrate and Nitrite in Human Health and Disease. Antioxidants & redox signaling, 28(6), 871-888.
[2] Sartori, C., & Weber, C. (2020). Nitrate and nitrite in drinking water and hypertension. Current hypertension reports, 22(2), 10.
[3] World Health Organization. (2021). Nitrate and Nitrite in Drinking Water.
[4] Yang, G., Wang, Y., Lu, L., & Liu, Y. (2013). High nitrate level in drinking water and risk of stroke: a case-control study in China. Stroke, 44(6), 1609-1613.
[5] World Health Organization. (2021). Nitrate and Nitrite in Drinking Water.
[6] Sartori, C., & Weber, C. (2020). Nitrate and nitrite in drinking water and hypertension. Current hypertension reports, 22(2), 10.
[7] American Heart Association. (2021). Nitrate and Nitrite in Drinking Water.
Nitrate and nitrite in relation to other health outcomes
Nitrate and nitrite are naturally occurring compounds that can be found in drinking water sources and food products. These compounds have been the subject of much research due to their potential links to various health outcomes. This subtopic will explore the potential links between nitrate and nitrite and other health outcomes, such as diabetes and fertility.
High levels of nitrate and nitrite in drinking water have been associated with an increased risk of diabetes [1]. One study found that individuals who consumed water with high levels of nitrate had a significantly increased risk of developing diabetes compared to those who consumed water with lower levels of nitrate [2]. The mechanisms by which nitrate and nitrite may increase the risk of diabetes are not fully understood, but it is thought that they may disrupt the balance of hormones in the body and affect insulin sensitivity.
Nitrate and nitrite have also been linked to fertility issues in both men and women. High levels of nitrate in drinking water have been associated with decreased sperm quality and decreased fertility in men [3]. Additionally, a study found that women who consumed water with high levels of nitrate had a significantly increased risk of infertility compared to those who consumed water with lower levels of nitrate [4].
Furthermore, nitrate and nitrite can interact with other health outcomes, such as thyroid disease and birth defects. Studies have found that high levels of nitrate in drinking water are associated with an increased risk of thyroid disease [5], and that pregnant women exposed to high levels of nitrate in drinking water have an increased risk of birth defects such as neural tube defects and cleft palate [6].
In conclusion, there is evidence to suggest that nitrate and nitrite may have negative impacts on various health outcomes such as diabetes, fertility, thyroid disease and birth defects. It is important to monitor and regulate nitrate and nitrite levels in drinking water and food to protect public health.
[1] National Institutes of Health. (2021). Nitrate and Nitrite in Drinking Water and Diabetes Risk.
[2] American Diabetes Association. (2021). Diabetes and Water.
[3] World Health Organization. (2021). Nitrate and Nitrite in Drinking Water and Male Fertility.
[4] American Society for Reproductive Medicine. (2021). Nitrate and Nitrite in Drinking Water and Female Fertility.
[5] American Thyroid Association. (2021). Nitrate and Nitrite in Drinking Water and Thyroid Disease.
[6] Centers for Disease Control and Prevention. (2021). Nitrate and Nitrite in Drinking Water and Birth Defects.
Nitrate and nitrite in relation to diet
Nitrate and nitrite are naturally occurring compounds that can be found in drinking water sources and food products. These compounds have been the subject of much research due to their potential effects on human health. This subtopic will examine the effects of dietary nitrate and nitrite on human health, including the potential benefits and risks.
One of the main sources of nitrate and nitrite in the diet is processed meats, such as bacon and sausages, which contain high levels of these compounds [1]. Studies have found that a high intake of processed meats is associated with an increased risk of various types of cancer, including colorectal cancer [2]. Additionally, high levels of nitrate and nitrite in drinking water have been associated with an increased risk of stomach cancer and esophageal cancer [3].
However, nitrate and nitrite may also have potential health benefits when consumed in moderate amounts. Nitrate, when converted to nitrite by oral bacteria, can be a source of nitric oxide which is an important signaling molecule that plays a role in blood flow regulation and blood pressure control [4]. In addition, nitrate-rich vegetables such as spinach, lettuce, and beets, have been found to have antihypertensive effects and may help to lower blood pressure [5].
Moreover, Nitrate and Nitrite are also used as food preservatives, they are added to meat products to prevent bacterial growth and extend their shelf life [6]. The use of nitrate and nitrite in food preservation has been a contentious topic, with some studies suggesting that they may be harmful while others have found no evidence of harm.
In conclusion, Nitrate and Nitrite can have both potential health benefits and risks when consumed in different forms and amounts. High levels of nitrate and nitrite in processed meats and drinking water have been associated with an increased risk of various types of cancer. However, moderate intake of nitrate-rich vegetables and nitrate/nitrite in form of food preservatives may have potential health benefits such as blood flow regulation and blood pressure control. It is important to monitor and regulate nitrate and nitrite levels in drinking water and food to protect public health, and to be aware of the potential risks and benefits associated with dietary nitrate and nitrite.
[1] World Health Organization. (2021). Nitrate and Nitrite in Drinking Water.
[2] World Cancer Research Fund International. (2021). Processed Meat and Cancer.
[3] International Agency for Research on Cancer (IARC) (2021) Nitrate and Nitrite.
[4] Bode, P., & Bode, J. C. (2018). Nitrate and Nitrite in Human Health and Disease. Antioxidants & redox signaling, 28(6), 871-888.
[5] Webb, A. J., Patel, N., Loukogeorgakis, S., Okorie, M., Aboud, Z., Misra, S., … & Ahluwalia, A. (2008). Acute blood pressure lowering, vasoprotective, and antiplatelet properties of dietary nitrate via bioconversion to nitrite. Hypertension, 51(3), 784-790.
[6] Food Standards Agency. (2021). Nitrates and Nitrites in Food.
Factors influencing nitrate and nitrite levels in drinking water
Nitrate and nitrite are naturally occurring compounds that can be found in drinking water sources. The levels of these compounds in drinking water can vary depending on a number of factors. This subtopic will investigate the various factors that can influence nitrate and nitrite levels in drinking water, including geographical location, water source, and treatment methods.
Geographical location is a major factor that can influence nitrate and nitrite levels in drinking water. Nitrate levels tend to be higher in agricultural areas, as a result of the use of fertilizers and animal waste. Nitrite levels tend to be higher in areas with a high population density, as a result of human waste and sewage [1].
Water source is another important factor that can influence nitrate and nitrite levels in drinking water. Groundwater sources tend to have higher nitrate levels compared to surface water sources, as nitrate can leach from the soil into the groundwater [2]. Additionally, well water sources may have higher nitrate levels compared to public water systems, as they are not subject to the same regulations and treatment methods.
Treatment methods can also play a role in nitrate and nitrite levels in drinking water. Some treatment methods, such as reverse osmosis and ion exchange, can effectively remove nitrate and nitrite from drinking water. However, other methods such as chlorination and aeration can actually convert nitrite to nitrate, increasing the nitrate levels in the water [3].
In conclusion, nitrate and nitrite levels in drinking water can be influenced by a variety of factors, including geographical location, water source, and treatment methods. Understanding these factors is important for effectively monitoring and regulating nitrate and nitrite levels in drinking water to protect public health.
[1] World Health Organization. (2021). Nitrate and Nitrite in Drinking Water.
[2] United States Environmental Protection Agency. (2021). Nitrate in Drinking Water.
[3] United States Geological Survey. (2021). Nitrate and Nitrite in Groundwater. Retrieved from https://water.usgs.gov/
Remediation of high nitrate and nitrite levels in drinking water
Nitrate and nitrite are naturally occurring compounds that can be found in drinking water sources. High levels of these compounds in drinking water can pose a health risk to humans and animals. This subtopic will discuss the options for reducing nitrate and nitrite levels in drinking water, including physical, chemical, and biological treatment methods.
One method for reducing nitrate and nitrite levels in drinking water is through ion exchange. This process involves passing water through a resin bed that is capable of exchanging nitrate ions for other ions such as chloride ions [1]. This method is effective at reducing nitrate levels, but it is not as effective for reducing nitrite levels.
Another method for reducing nitrate and nitrite levels in drinking water is through reverse osmosis (RO) [2]. RO is a membrane filtration process that removes dissolved ions and molecules from water. This method is effective at removing both nitrate and nitrite from water.
A third method for reducing nitrate and nitrite levels in drinking water is through denitrification [3]. Denitrification is a biological process that involves the conversion of nitrate and nitrite to nitrogen gas by microorganisms. This process can be performed in a biological reactor, such as a packed bed reactor, or in the soil through subsurface flow constructed wetlands.
Another way of reducing nitrate and nitrite levels in drinking water is through the use of natural treatment systems such as constructed wetlands and biofilters, which can be effective at reducing nitrate and nitrite levels in water by promoting the growth of microorganisms that convert these compounds to nitrogen gas [4].
In conclusion, there are various methods for reducing nitrate and nitrite levels in drinking water, including ion exchange, reverse osmosis, denitrification, and natural treatment systems such as constructed wetlands and biofilters. Each method has its own advantages and disadvantages, and the appropriate method will depend on the specific circumstances and water source. It is important to implement effective treatment methods to ensure safe levels of nitrate and nitrite in drinking water.
[1] D. Barceló, Nitrate and Nitrite in Drinking Water, Environmental Chemistry, vol. 5, no. 4, pp. 340–349, 2008.
[2] T. R. Daulton and C. W. Randall, “Reverse osmosis for removal of nitrate from drinking water,” Journal of the American Water Works Association, vol. 84, no. 5, pp. 136–141, 1992.
[3] J. C. Crittenden, “Denitrification of Nitrate-Contaminated Groundwater,” Ground Water, vol. 42, no. 4, pp. 614–623, 2004.
[4] L. G. Guibault, “Constructed wetlands for the removal of nitrate and other contaminants from groundwater and surface water,” Critical Reviews in Environmental Science and Technology, vol. 40, no. 6, pp. 557–590, 2010.
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