The Broad Scope of Health Effects From Chronic Arsenic Exposure

Update on a Worldwide Public Health Problem

Marisa F. Naujokas; Beth Anderson; Habibul Ahsan; H. Vasken Aposhian; Joseph H. Graziano; Claudia Thompson; William A. Suk


Environ Health Perspect. 2013;121(3):295-302. 

In This Article

Abstract and Introduction


Background: Concerns for arsenic exposure are not limited to toxic waste sites and massive poisoning events. Chronic exposure continues to be a major public health problem worldwide, affecting hundreds of millions of persons.

Objectives: We reviewed recent information on worldwide concerns for arsenic exposures and public health to heighten awareness of the current scope of arsenic exposure and health outcomes and the importance of reducing exposure, particularly during pregnancy and early life.

Methods: We synthesized the large body of current research pertaining to arsenic exposure and health outcomes with an emphasis on recent publications.

Discussion: Locations of high arsenic exposure via drinking water span from Bangladesh, Chile, and Taiwan to the United States. The U.S. Environmental Protection Agency maximum contaminant level (MCL) in drinking water is 10 μg/L; however, concentrations of > 3,000 μg/L have been found in wells in the United States. In addition, exposure through diet is of growing concern. Knowledge of the scope of arsenic-associated health effects has broadened; arsenic leaves essentially no bodily system untouched. Arsenic is a known carcinogen associated with skin, lung, bladder, kidney, and liver cancer. Dermatological, developmental, neurological, respiratory, cardiovascular, immunological, and endocrine effects are also evident. Most remarkably, early-life exposure may be related to increased risks for several types of cancer and other diseases during adulthood.

Conclusions: These data call for heightened awareness of arsenic-related pathologies in broader contexts than previously perceived. Testing foods and drinking water for arsenic, including individual private wells, should be a top priority to reduce exposure, particularly for pregnant women and children, given the potential for life-long effects of developmental exposure.


Ongoing exposures to toxic chemicals such as arsenic continue to pose a significant threat to public health. The World Health Organization (WHO) estimates that > 200 million persons worldwide might be chronically exposed to arsenic in drinking water at concentrations above the WHO safety standard of 10 μg/L (WHO 2008) ( Table 1 ). Arsenic is a metalloid element that is encountered primarily as arsenical compounds. Within these compounds, arsenic occurs in different valence states, the most common of which are AsIII (arsenites) and AsV (arsenates). Arsenic in drinking water is typically found in the inorganic form, either as AsIII or AsV, whereas arsenic in food is found in the organic and inorganic forms, depending on the specific food [Agency for Toxic Substances and Disease Registry (ATSDR) 2007; European Food Safety Authority (EFSA) 2009] Sources of arsenic contamination include natural deposits as well as anthropogenic sources such as mining and electronics manufacturing processes and metal smelting (ATSDR 2007).

Arsenic holds the highest ranking on the current U.S. ATSDR 2011 substance priority list (ATSDR 2011b) ( Table 2 ). ATSDR ranks chemicals using an algorithm that translates potential public health hazards into a points-scaled system based on the frequency of occurrence at National Priority List (NPL) Superfund sites as well as toxicity and potential for human exposure. Arsenic tops the list in spite of the fact that this ranking does not include full consideration of exposure from drinking water, diet, copper-chromated arsenic-treated wood, coal- and wood-burning stoves, arsenical pesticides, and homeopathic remedies (ATSDR 2007, 2011b; Akter et al. 2005; EFSA 2009; Rose et al. 2007). Therefore, the threat to human health posed by arsenic is even greater than its top ATSDR ranking would suggest. In regard to toxicity, the International Agency for Research on Cancer (IARC) defines arsenic as a Group I known human carcinogen that also induces a wide array of other noncancer effects, leaving essentially no bodily system free from potential harm (ATSDR 2007; IARC 2012; National Research Council 2001; WHO 2008).

Here we synthesize the large body of current research pertaining to arsenic exposure and health effects and emphasize the broadening scope of predicted and observed impacts of arsenic on public health. Understanding the wide range of these impacts drives home the importance of testing drinking-water sources and monitoring foods for arsenic. Whereas municipalities test public drinking-water sources, private wells can go untested. Recent data also raise concerns for arsenic exposure via foods including rice and organic brown rice syrup [Davis et al. 2012; EFSA 2009; Food and Drug Administration (FDA) 2012; Gilbert-Diamond et al. 2011; Jackson et al. 2012] as well as chicken feather meal products that are used in the human food system (Nachman et al. 2012).

Even as assessments of dietary exposure continue to unfold, drinking water remains a major concern for arsenic exposure. There are known, large-scale drinking-water contamination problems in countries such as Bangladesh (Ahsan et al. 2006; Argos et al. 2010, 2012; Smith et al. 2000b). However, chronic arsenic exposure is a concern in many parts of the world ( Table 1 ). For example, arsenic concentrations in drinking water from some private wells in the United States are as high as 3,100 μg/L, which is in the range of the highest concentrations reported in Bangladesh (Nielsen et al. 2010; Yang et al. 2009). Yet detection of arsenic contamination even at these high levels remains problematic because it is tasteless, colorless, and odorless.

Given the large number of studies that address the broad range of information provided here, it is impractical to include all pertinent studies. Rather, we present a synthesis of information and cite recent studies that help illustrate the breadth and scope of the problems. When available, we cite current reviews that can serve as a resource for a more complete listing of relevant resources, most often focusing on single health issues such as cardiovascular disease (States et al. 2009). Detailed discussions of arsenic exposure and health effects can be found elsewhere (ATSDR 2007; EFSA 2009; Gibb et al. 2011; States et al. 2011).

As awareness of arsenic exposure increases, so should knowledge of its health effects because the impact of chronic arsenic exposure on public health is substantial. In addition to skin lesions and skin cancer (ATSDR 2011a; Sengupta et al. 2008; Smith et al. 2000a), neurological, respiratory, cardiovascular, and developmental effects and more are linked to chronic arsenic exposure ( Table 3 ) (Argos et al. 2012; Smith and Steinmaus 2009; States et al. 2011). Acute poisonings still occur but are uncommon (Bronstein et al. 2011). Arsenic renders its toxicity via numerous mechanisms: Arsenic is genotoxic and has multiple effects on cellular signaling, cellular proliferation, DNA structure, epigenetic regulation, and apoptosis (Flora 2011; Ren et al. 2011; States et al. 2011).

A wealth of data comes from ongoing epidemiological studies of large populations exposed to a wide range of arsenic levels in drinking water in regions such as Taiwan, Bangladesh, Chile, India, and Argentina (Ahsan et al. 2006; Argos et al. 2012; Chen CL et al. 2010a; Smith et al. 2011; Yuan et al. 2010). In Taiwan, a stable population in an arsenic-endemic region had been exposed to arsenic via drinking water since the 1900s [Chen CJ et al. 1988b, 1992; Gibb et al. 2011; Tseng 1977; U.S. Environmental Protection Agency (EPA) 2001; Wu et al. 1989]. In Bangladesh, tube wells were dug in the 1970s as a source of drinking water to avoid microbial contamination, only to later learn that the tube wells are contaminated with naturally occurring arsenic (Smith et al. 2000b). Researchers established a cohort in Bangladesh with over 10,000 persons enrolled as part of the Health Effects of Arsenic Longitudinal Study (HEALS) (Ahsan et al. 2006; Argos et al. 2012). Researchers are also studying a population in Chile where some cities were exposed to high concentrations of arsenic for a defined, limited period of time (1958–1971), at which point, systems were installed to remove arsenic from drinking water (Biggs et al. 1998). This population is particularly well suited for studies related to latency periods for chronic diseases and susceptibility during development (Dauphine et al. 2011; Liaw et al. 2008; Marshall et al. 2007; Yuan et al. 2010). Major findings from these cohorts and other studies are described in the following sections.

In light of accumulated research, there is increasing awareness that arsenic exposure might be affecting more persons and contributing to more chronic disease than previously thought. In the HEALS cohort, approximately 21.4% of all deaths and 23.5% of deaths associated with chronic disease could be attributed to arsenic at > 10 μg/L in drinking water (Argos et al. 2010). Here we present an overview and synthesis of recent information on worldwide concerns for arsenic exposures and public health. The enormity of potential public health impacts is striking. Given this potential, testing and remediating arsenic in drinking water at the level of single private wells and reducing dietary exposure are critical to protecting public health.