DESCRIPTION (provided by applicant): Little is known about the consequences of early life exposure to most common environmental chemicals, including arsenic. This constitutes a critical gap in knowledge, since our recent findings from Chile suggest that early life exposure to arsenic results in disturbing increases in young adult mortality from several cancers, including lung cancer, bladder cancer, kidney cancer, as well as non-cancer causes of death, including myocardial infarction, chronic renal failure and chronic respiratory disease. Arsenic is a remarkable toxicant already known to affect multiple organ systems in exposed adults, including increased incidence of several cancers, cardiovascular disease, chronic respiratory disease and diabetes. We have been following a cohort of 650 children in Bangladesh, approximately half of whom had a wide range of exposure to arsenic in drinking water in early life, up to 1000 μg/L, while the other half were never exposed to more than 10 μg/L in water. To date, our focus has been on respiratory disease, and we have found a marked increase in respiratory symptoms in the exposed children at ages 7-17 years, including wheezing and shortness of breath. We propose to continue following this unique cohort of children, not only to look for progression of respiratory disease, but also to add additional markers of early life effects for several other important chronic diseases. These include early markers and risk factors for cardiovascular disease (blood pressure, serum lipids, body mass index, and hemoglobin), diabetes (fasting blood sugar and glycosuria), and chronic renal effects (creatinine and serum ß2-microglobulin). We also plan a pilot investigation of arsenic in deciduous teeth as a biological marker for in utero and early childhood exposure. Studying the effects of early life arsenic exposure is a public health priority, since millions of pregnant mothers and children in the US and worldwide are exposed to arsenic in drinking water above the current drinking water standard of 10 μg/L. If further study confirms our preliminary evidence that early life exposure is important to the long-term health of exposed children, then much more attention must be paid to preventing early life arsenic exposure.

PUBLIC HEALTH RELEVANCE: We propose to continue our previous study of the effects of early life arsenic exposure on lung health, with 3 years of further follow-up, and the addition of important new health outcomes including early biomarkers of cardiovascular disease, renal disease and diabetes.