Long-Term Effect of Early-Life Arsenic Exposure on Morning Plasma Cortisol in Adults from Antofagasta, Chile

Over 100,000 people were exposed to arsenic-contaminated drinking water in Antofagasta, Chile from 1958-1970. Individuals born during this high exposure period have elevated rates of cancer, lung and cardiovascular disease, and hypertension. However, the mechanisms of long-term arsenic toxicity remain unclear. We investigated whether early-life arsenic exposure was associated with altered glucocorticoid levels in adulthood. This study included 114 individuals born in Antofagasta during the high exposure period and 118 individuals born elsewhere. Arsenic exposure metrics were constructed based on residential histories and included: concentration at birth, peak and highest 5-year average between ages 0-10 years, and highest lifetime 5-year average, and lifetime cumulative exposure. Morning plasma cortisol concentrations were measured using a cell-based bioassay. Individuals in the highest quartile of highest lifetime 5-year average of arsenic exposure had approximately 11% lower mean log cortisol levels than those in the lowest quartile of exposure ({beta} = -0.116; 95% CI: -0.229, -0.003). In sex-stratified analyses, associations were stronger among females. For example, females in the highest quartile of cumulative exposure had 22.0% lower cortisol levels compared to those in the lowest quartile ({beta} = -0.248; 95% CI: -0.444, -0.053) and the test for interaction by sex was statistically significant (p = 0.036). This study is the first to show that early-life arsenic exposure may have lasting effects on cortisol. These findings highlight endocrine disruption as a mechanism contributing to long-term health effects of early arsenic exposure.