, 2006). The current EPA RfD of 0.3 μg/kg-day derived from a NOAEL for skin lesions in SW Taiwan incorporates an uncertainty factor of 3, based on insufficient data to preclude reproductive toxicity and potential variation in individual sensitivity (EPA, 1993). EPA, however, noted a lack of clear consensus among agency scientists and that strong scientific arguments could support values between 2 and 3 of the RfD (i.e., from 0.1 μg/kg-day to 0.8 μg/kg-day). In evaluating a specific RfD for CVD, however,

other endpoints such as reproductive toxicity (except for effects related to CVD) would not be considered. The SGLT inhibitor available evidence for potential individual differences in sensitivity to arsenic indicates that the Bangladesh population would be more sensitive than the U.S. population PD-0332991 ic50 based on a number of factors. South Asians are reported to be susceptible to coronary artery disease, and Bangladeshis are reported to be even more prone to heart disease, even when living abroad in countries such as the United States or United Kingdom (Islam and Majumder, 2013). In addition to having some of the common risk factors, heart disease may be increased in Bangladeshis by nutritional deficiencies and related conditions (e.g., hyperhomocysteinemia), low birth weight and childhood malnutrition,

high prevalence of betel nut use, and possibly genetic susceptibility (Gamble et al., 2005a, Islam and Majumder, 2013 and Pilsner et al., 2009). Consistent with lower intakes of folate as noted previously, folate biomarkers were lower in Bangladesh than in the U.S. population. Idoxuridine Median plasma/serum folate levels among controls without skin lesions in a subgroup of the HEALS cohort (3.4 ng/mL) (Pilsner et al., 2009) and

in a larger portion of the cohort (4.6 ng/mL in women, 3.7 ng/mL in men) (Gamble et al., 2005a) were considerably lower than in the United States (median in 2005–2006 of 12.2 ng/mL) (McDowell et al., 2008). The prevalence of a low serum folate level (<3 ng/mL) is less than 1% in the U.S. population (McDowell et al., 2008). Although elevated arsenic exposure may also contribute to lower folate levels in HEALS participants, the relatively weak inverse correlation between water arsenic concentration and folate levels (r = −0.13) ( Gamble et al., 2005b), indicates an overall reduced folate intake in Bangladesh relative to the United States. Lack of folic acid fortification of foods in Bangladesh is also compounded by traditional cooking practices involving prolonged cooking, which can oxidize up to 95% of the naturally occurring folate in foods (FAO, 2001 and Gamble et al., 2005a). By contrast, folic acid is much more resistant to oxidation and has nearly 100% bioavailability compared to 25–50% for natural folate in foods (FAO, 2001). In the HEALS cohort, plasma folate levels were correlated with urinary arsenic forms in the expected directions for impairment of arsenic methylation (i.e.