Table of Contents
Background
Arsenic (As) is a naturally occurring metalloid found in various environmental compartments including soil, rocks, air, and water. Its occurrence in drinking water has remained a serious public health concern for many decades since millions of people throughout the globe have been consuming As contaminated drinking water. As can also cause food chain contamination once uptaken by the plants or seafood contamination. Although anthropogenic sources such as industrial and agricultural activities, smelting, household plumbing, and waste recycling and dumping areas also contribute to drinking water contamination. Further, its organic forms including arsenobetaine and arsenocholine are reported to be found in seafood and are considered less toxic compared to the other arsenicals.
However, it is believed that natural contamination through the process mainly including geological weathering, and physicochemical interaction such as pH, redox potential, etc. contributes to the major drinking water Arsenic contamination. Much of the research on this topic has mainly focused on the investigation of the toxic impacts of As among the population consuming drinking water with elevated As levels. To address this concern, World Health Organization (WHO) and USEPA have set the MCL of 10 ppb (µg/L) for total As in drinking water. It is interesting to note that As toxicity mainly depends on its oxidation state and forms. Inorganic As exists in two forms including trivalent arsenite (As+3) and Pentavalent arsenate (As+5).
Among these, the trivalent form is considered more toxic compared to the pentavalent one and possesses the potential to alter cellular processes resulting in various health implications. Other forms of As include methylated species in the form of monomethyl arsenate (MMA) and dimethyl arsenate (DMA) which are also very toxic to humans. It is interesting to mention that the two methylated arsenicals i.e. MMA and DMA also have trivalent and pentavalent forms including MMA+3, MMA+5, DMA+3, and DMA+5 respectively and each specie possesses distinct toxic potential. These peculiar properties or As makes it the king of poisons due to which many international health agencies and organizations classify As in their top priority list. For example, the International agency for research on cancer (IARC) has classified As as a class I carcinogen.
Moreover, scientific evidence also suggests that As can be toxic even at very low concentrations (below MCL) if consumed for a prolonged period and can cause health issues. Major regions of the world reported above-MCL As levels include the US, Bangladesh, India, Mexico, Argentina, China, and Pakistan. EPA has identified many areas in the US containing high As levels than the MCL in the water reservoirs. Although the water supply system throughout the US ensures a safe drinking water supply to the residents after proper treatment. However, regular monitoring of drinking water is very much necessary to ensure that the supplied drinking water is free of As. In addition to federal regulations for As, some states have set their own MCL for As to ensure a contaminant-free drinking water supply. For example, New Jersey (NJ) has set an MCL of 5 µg/L for As in drinking water.
Long-term exposure to drinking water As has been associated with various health effects in population studies comprising cross-sectional, longitudinal, and hospital-based studies. These adverse health effects are further related to socio-demographic factors such as age, gender, BMI, exposure concentration, and duration. Among the known health implications associated with drinking water As include skin lesions, immune system effects, cancer, cardiovascular, renal, and hepatic diseases, neurological impairments, and diabetes. Given the extent of the toxicity and associated adverse health impacts, it is very much necessary to regularly monitor drinking water As levels in the US to keep the public safe from its toxic effects. If the water contains elevated As than the MCL, it should be suitably communicated with the consumers and should be supplied after proper treatment by adopting recommended treatment strategy.
Literature suggests that As can be toxic to humans at any age ranging from the pre-natal stage to old age. Among these, children and older people are more susceptible to As toxicity because of biological development and weak immune system respectively. Moreover, studies also suggest that co-exposure of As with other contaminants such as fluoride (F) and other metals in drinking water can be more toxic due to synergistic toxic mechanisms (Tian et al. 2023; Wang et al. 2007). As described, As can occur in various oxidation forms in drinking water, further, the mechanisms of As metabolism and toxicity are so complex due to the chemical properties that it has not been completely understood so far despite numerous epidemiological studies (Hopenhayn 2006; Ozturk et al. 2022).
However, scientists have proposed some mechanisms related to As toxicity through which As can show toxic behavior by affecting the cellular and molecular machinery (Hughes 2002). These suggested mechanisms mainly included DNA damage, cell proliferation, genetic polymorphism, altered As metabolism, altered gene expression and regulation, epigenetic changes mainly including DNA methylation and miRNA, oxidative stress, etc. (Rahaman et al. 2021). Through these suggested mechanisms, it is believed that As can take control of cellular and enzymatic machinery and results in various symptoms depending on levels, exposure duration, and the individual’s susceptibility and nutritional status. Metabolism of As in the human body is rather a complex process and involves various biotransformation processes. This includes a series of metabolic reactions involving methylation, reduction, and oxidation that convert inorganic As into its organic and inorganic forms (Chen and Costa 2021). The main purpose of this biotransformation is to facilitate As excretion from the urine without being bioaccumulated in human tissues and organs.
This mainly involves the methylation reactions by adding a methyl group (CH3) to the inorganic As by the enzyme As(+3) methyltransferase (As3MT). The introduction of omics technologies in recent years using the integration of genome and metabolome-wide responses in human biological samples e.g. blood, urine using state-of-the-art analytical platforms such as DNA microarrays, next-generation sequencing (NGS) and liquid chromatography coupled with high-resolution mass spectrometry (LC-HRMS) has made better understandings of As-related toxic mechanisms. Furthermore, a combination of these analytical approaches in combination with bioinformatics and systems biology has developed has identified numerous biological pathways and genetic changes which are associated with long-term As exposure (Rehman et al. 2022; Rehman et al. 2020). The majority of epidemiological studies in this context have investigated the molecular responses in human blood. It is necessary to investigate tissue-specific As a response to better understand the mechanisms associated with As toxicity.

Detection Methods and Removal Strategies
Arsenic can be detected in drinking water using various analytical methods. For large-scale monitoring comprising testing water of household wells, a quick and cost-effective field kit method with reliable results has been developed recently. The method has been widely applied in developing countries to monitor elevated As levels in drinking water (Baghel et al. 2007). Spectrophotometric methods involving the addition of a reagent in the water sample are also common and give estimated As concentrations in a given sample (Morita and Kaneko 2006). More sensitive As quantification methods comprise atomic absorption spectrophotometer (AAS) coupled with hydride generation (HGAAS) or graphite furnace (GFAAS). The method can detect As in drinking water up to ppb levels.
Some modifications in the HGAAS system such as cold trapping/cryo-traping (HG-CT-AAS) can give more reliable results for As levels in drinking water as well as in biological specimens (Hernández-Zavala et al. 2008). Inductively coupled plasma (ICPMS) is a more sensitive method but on the other hand, it is costly compared to AAS and is preferred where detection levels in drinking water are very low. To quantify organic species of As i.e. MMA and DMA, ICP and AAS are also coupled with high-performance liquid chromatography (HPLC) to simultaneously quantify organic and inorganic As species (Ronkart et al. 2007). Furthermore, biosensors have been developed recently that use certain biological components including enzymes, antibodies, and microbes to detect As the presence in drinking water (Joshi et al. 2009). The choice of preference for As detection mainly depends on desired sensitivity, laboratory equipment, and affordability of quantification.
Elevated As can be removed from drinking water to make consumable by adopting various removal approaches depending on the affordability and cost effectiveness. Among widely practiced methods for As removal include coagulation-filtration which involve addition of Al or Fe-based coagulants to the water resulting in precipitation of dissolved As in water that can be removed through filtration (Song et al. 2006; Wickramasinghe et al. 2004). Activated alumina, carbon, and FeOH as an adsorbent material are also an effective ways to remove As from water (Liu and Qu 2021). Among other As removal methods include the biological removal involving microorganisms that can convert As to arsenate and removed using coagulation, filteration or adsorption (Maity et al. 2021). Biochar application has also been used recently for As removal and is proven an effective method to treat As-contaminated water (Amen et al. 2020). Reverse osmosis (RO) is although a costly approach but widely used method to remove As as well as many other environmental contaminants in water including the microorganisms (Abejón et al. 2015).

Public Perspective
Following frequently asked questions (FAQs) try to address some general public concerns in the US, especially the NYC and NJ region.
Scientific evidence suggest that long-term exposure to low levels of inorganic As in drinking water is known to cause human health problems including cancer and non-cancerous diseases in humans.
As enters lakes, rivers and underground water reservoirs through natural processes when mineral deposits such as rocks containing As erode and dissolve. It may also enter the groundwater through the discharge of industrial and agricultural waste products. However, it is believed that the natural contamination accounts most compared to the anthropogenic sources.
Many regulatory bodies throughout the world including USEPA and WHO has regulated As levels in drinking water by setting an MCL of 10 µg/L. IARC has classified As a class I carcinogen due to high scientific evidence available for As toxicity.
The symptoms associated with As poisoning can range from general including nausea, vomiting and headache to organs specific. Long-term As exposure can damage human organs specifically skin, liver, kideneys as well as the systems including immune system, cardiovascular, and nervous system. As can also results in decreased RBCs and WBCs production causing fatigue and illnesses.
Unfortunately, there is no way to know the As level in water before a well is drilled or tested by authorized experts. As levels can vary between wells, even within a small area. You cannot taste, see, or smell As in your water.
The regulated level of As in drinking water is 10 ppb, anything above this limit can cause adverse health impacts among all age groups especially children and older people. Level, exposure duration and individual susceptibility plays key role in determining extent of As toxicity. Some studies also suggest that As can be toxic even at very low concentrations for prolonged periods therefore, a regular testing and monitoring of water wells is warranted where As is reported to be higher in drinking water.
Major part of ingested As is excreted through the urine after being filtered from the kidneys. Humans excrete a mixture of inorganic, monomethylated, and dimethylated (but not trimethylated) forms of arsenic. The pentavalent metabolites MMA+5 and DMA+5 are less toxic than arsenite or arsenate. Approximately 50% of excreted arsenic in human urine is dimethylated and 25% is monomethylated, with the remainder being inorganic As. However, variations may exist among individuals depending on susceptibility and metabolism.
Although commercial kits to test As have been developed recently but it is highly recommended to get your water tested by an expert and certified companies to get reliable results.
Yes, there are various methods developed such as reverse osmosis (RO) that can completely remove As from drinking water.
As has no smell or taste, so you cannot tell if it is in your drinking water. The only way to find out if your well water has high As is to have it tested.

Conclusion
As is a toxic metalloid that exists in various forms in drinking water and is a global public health concern with an MCL of 10 ppb in drinking water set by WHO, EPA, and many regulating bodies. It can adversely affect human health via drinking water exposure through various proposed mechanisms. The US drinking water has been reported to contain above-MCL As levels. Water supply systems ensure neat and As-free drinking water to US residents however, regular water testing and monitoring should be performed to ensure a safe drinking water supply and take appropriate treatment measures to reduce the high As levels before its supply to the consumers.
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- Yasir A. Rehman, Ph.D.
Dr. Rehman was born in Rawalpindi, Pakistan. He completed his MSc from PMAS – Arid Agriculture University Rawalpindi in 2011 where his thesis comprised a health risk assessment of subjects living in the vicinity of wastewater channels in urban settings and its relationship with the incidence of Malaria.
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