Arsenic and subclinical vascular damage in a sample of Italian young adults: a cross-sectional analysis

The European Commission asked EFSA to update its 2009 risk assessment on arsenic in food carrying out a hazard assessment of inorganic arsenic (iAs) and using the revised exposure assessment issued by EFSA in 2021. Epidemiological studies show that the chronic intake of iAs via diet and/or drinking water is associated with increased risk of several adverse outcomes including cancers of the skin, bladder and lung. The CONTAM Panel used the benchmark dose lower confidence limit based on a benchmark response (BMR) of 5% (relative increase of the background incidence after adjustment for confounders, BMDL05) of 0.06 μg iAs/kg bw per day obtained from a study on skin cancer as a Reference Point (RP). Inorganic As is a genotoxic carcinogen with additional epigenetic effects and the CONTAM Panel applied a margin of exposure (MOE) approach for the risk characterisation. In adults, the MOEs are low (range between 2 and 0.4 for mean consumers and between 0.9 and 0.2 at the 95th percentile exposure, respectively) and as such raise a health concern despite the uncertainties.

Arsenic has been associated with significant effects on human health. Exposure to inorganic arsenic has been associated with the changes in gene expression. Promoter of CDKN1A antisense DNA damage activated RNA (PANDAR) expression is induced by p53 protein and DNA damage response. Here, we investigated whether the ability of arsenic metabolism in individuals affected the expression of PANDAR, DNA damage, and DNA methylation. Levels of gene expression and DNA damage were examined by the quantitative polymerase chain reaction and DNA methylation was measured by the methylation-sensitive high-resolution melting curve. In our study, we demonstrated that arsenic exposure increased PANDAR expression and DNA damage among arsenic smelting plant laborers. The PANDAR expression and DNA damage were positively linked to monomethylarsonic acid % ( R = 0.25, p < 0.05 and R = 0.32, p < 0.01) and negatively linked to dimethylarsinic acid % ( R = −0.21, p < 0.05 and R = −0.31, p < 0.01). Subjects with low primary methylation index had increased levels of DNA damage (51.62 ± 2.96 vs. 60.93 ± 3.10, p < 0.05) and methylation (17.14 (15.88–18.51) vs. 15.83 (14.82–18.00), p < 0.05). Subjects with low secondary methylation index had increased levels of PANDAR expression (4.88 ± 0.29 vs. 4.07 ± 0.23, p < 0.01) and DNA damage (17.38 (15.88–19.29) vs. 15.83 (14.82–17.26), p < 0.01). DNA methylation of PANDAR gene was linked to the regulation of its expression in peripheral blood lymphocytes among laborers ( Y = −2.08 × X + 5.64, p < 0.05). These findings suggested arsenic metabolism ability and exposure affected the expression of PANDAR, DNA damage, and DNA methylation.

The results suggest an effect on skin diseases and circulatory system diseases and, considering the relative young age of cohort members, they could be considered also as predictive of future severer diseases.