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

Disclosures

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

In This Article

Varied Susceptibilities

Genetic and Nutritional Factors in Susceptibility

The variety of biological systems often simultaneously affected by arsenic is further complicated by varied individual susceptibilities to its toxic effects. For example, interindividual variation in the ability to methylate arsenic is associated with differential susceptibility to the effects of arsenic exposure (Hall and Gamble 2012; Steinmaus et al. 2010). Genetic polymorphisms have also been shown to be a contributing factor (Agusa et al. 2012; Ahsan et al. 2007; Applebaum et al. 2007; Argos et al. 2012; Pierce et al. 2012; Porter et al. 2010; Reichard and Puga 2010). A recent large, comprehensive genome-wide association study identified specific genetic variations associated with risk for skin lesions as well as differences in arsenic metabolism (Pierce et al. 2012). Evidence is also building that nutritional factors, notably folate, appear to play an important role in arsenic methylation and elimination (Basu et al. 2011; Chen Y et al. 2009; Gamble et al. 2007; Hall and Gamble 2012; Pilsner et al. 2009). For example, low folate and hyperhomocysteinemia are associated with increased risk of skin lesions (Pilsner et al. 2009). Together, current information about arsenic metabolism across individuals sheds light on possibilities for new strategies for the prevention and amelioration of the toxicity of arsenic.

Susceptibility During Development and Long-term Latency

Adverse pregnancy and developmental outcomes are associated with early-life exposure to arsenic (Vahter 2008). Arsenic exposure is significantly associated with increased infant mortality and, in some studies, increased spontaneous abortion and stillbirth (Milton et al. 2005; Rahman et al. 2010a; von Ehrenstein et al. 2006) as well as reduced birth weight (Rahman et al. 2009). Early-life arsenic exposure is also associated with neurological impairments in children (Hamadani et al. 2011; Parvez et al. 2011; Wasserman et al. 2004, 2007). For example, motor function in children, as well as verbal and full-scale IQ in girls, are both inversely associated with arsenic exposure (Hamadani et al. 2011; Parvez et al. 2011). Prenatal exposure also affects the developing immune system. Maternal urinary arsenic concentrations are associated with increased inflammation as well as altered cytokine profiles in cord blood and reduced thymus size and function in newborns (Ahmed et al. 2011, 2012). Altered immune responses are consistent with the observation of increased risk for lower respiratory infections and diarrhea in infants with increasing arsenic exposure (Rahman et al. 2010b).

The impacts of early-life arsenic exposure can continue into adulthood (Vahter 2008). Exposure during pregnancy and childhood is associated with an increased occurrence and/or severity of lung disease, cardiovascular disease, and cancer in childhood and later in life, with evidence of decades-long latency periods for these health conditions (Table 4) (Dauphine et al. 2011; Liaw et al. 2008; Marshall et al. 2007; Smith et al. 2011; Yuan et al. 2010). Childhood liver cancer MRRs were 9–14 times higher for those exposed as young children as compared with controls (Liaw et al. 2008). Other reports of latency periods extending over 50 years include skin cancer (Haque et al. 2003), urinary cancers (Bates et al. 2004; Chen CL et al. 2010b; Marshall et al. 2007; Su et al. 2011), and lung cancer (Marshall et al. 2007; Su et al. 2011). For example, peak SMRs for childhood liver cancer and bronchiectasis were 14.1 and 50.1 times higher, respectively, for individuals exposed to arsenic in utero and during childhood as compared with individuals exposed during other periods of their lives (Table 4) (Smith et al. 2006). Bladder cancer mortality peaked 25–36 years from the initiation of exposure (Marshall et al. 2007), and kidney cancer MRR peaked 21–25 years from initiation of exposure and was highest for women (Yuan et al. 2010). Regarding noncancer health effects, early-life arsenic exposure is associated with increased adult mortality from pulmonary tuberculosis (Smith et al. 2011), bronchiectasis (Smith et al. 2006), and myocardial infarction (Yuan et al. 2007).

Together the data indicate a sensitivity during development to health effects that can be long lasting and latent for > 50 years. The implications are profound and make it clear that every effort should be made to prevent exposure of pregnant women, women of childbearing age, infants, and children to arsenic in order to prevent a multitude of health effects, particularly cancer, later in life.

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