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Extramural Papers of the Month

By Jerry Phelps
July 2010

Arsenic-Related Mortality in Bangladesh

NIEHS-supported researchers report that 21.4 percent of all deaths in the Araihazar region of Bangladesh can be attributed to well water arsenic concentrations greater than 10 micrograms per liter (mg/L). Their findings are from the first prospective study to investigate the link between arsenic exposure and mortality and are published online in The Lancet.

Current estimates suggest that 35-77 million of the 125 million inhabitants of Bangladesh drink arsenic-contaminated water. More than 55 percent of the 11,746 study participants drink water with more than 50 mg/L, the current Bangladesh standard, and 75 percent consume water which is more contaminated than the World Health Organization standard of 10 mg/L. However, a unique feature of this study is that it includes participants at both the low and high ends of the dose-response curve. For people exposed to the highest doses of arsenic, all-cause mortality was nearly 70 percent higher relative to those exposed to less than 10 mg/L.

Arsenic-contaminated drinking water is an environmental health problem in many parts of the world, including some areas of the United States. The investigators plan follow-up studies to assess other long-term effects of arsenic exposure and how they might be ameliorated by changes in exposure. However, they point out that "solutions and resources are urgently needed to mitigate the resulting health effects of arsenic exposure."

Citation: Argos M, Kalra T, Rathouz PJ, Chen Y, Pierce B, Parvez F, et al.( Exit NIEHS 2010. Arsenic exposure from drinking water, and all-cause and chronic-disease mortalities in Bangladesh (HEALS): a prospective cohort study. Lancet. Epub ahead of print. doi:10.1016/S0140-6736(10)60481-60483. (Story}

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Flame Retardant Linked to Decreased Thyroid Hormone Levels in Pregnant Women

In the largest study conducted to date, researchers at the University of California Berkeley report that exposure to flame retardant compounds is associated with decreased levels of thyroid-stimulating hormone (TSH) around the beginning of the third trimester of pregnancy. The risk of sub-clinical hyperthyroidism was also associated with exposure.

Polybrominated diphenyl ethers or PBDEs are used as flame retardants in a variety of products including textiles, furniture, automobiles, airplanes, and electronics. PBDEs are lipophilic and bioaccumulate in wildlife and humans, and also biomagnify up the food chain. They are found in almost all human beings on earth and their concentration in human serum and breast milk has increased exponentially in the last three decades. They are persistent compounds with half-lives ranging from two to twelve years.

The research team measured PBDE and thyroid hormone levels in 270 pregnant women, most of whom were Mexican American. Lab analyses showed that women with higher levels of PBDEs had lower levels of TSH.

These findings are important because of the important role that maternal thyroid hormone levels play in fetal development. Future studies planned by the team will examine whether subclinical hyperthyroidism and maternal exposure to PBDEs are associated with adverse pregnancy outcomes such as preeclampsia, premature birth, and low birth weight.

Citation: Chevrier J, Harley KG, Bradman A, Gharbi M, Sjödin A, Eskenazi B. 2010. Polybrominated diphenylether (PBDE) flame retardants and thyroid hormone during pregnancy. Environ Health Perspect. Epub ahead of print. doi:10.1289/ehp.1001905.

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Solutions to Arsenic Groundwater Contamination

According to the World Health Organization, approximately 60 million people living in Bangladesh, or about half the population, drink water contaminated with unsafe levels of arsenic, defined as greater than 10 micrograms per liter. The contamination puts people at high risk for cancer, diabetes, and other serious diseases. A new NIEHS-funded review article examines variations in groundwater arsenic in South and Southeast Asia and makes recommendations for reducing exposures in the region.

In Bangladesh, wells that tap into deep aquifers are typically uncontaminated and provide safe drinking water. However, in recent years, farmers have started to drill deep wells for irrigation, which can compromise access to clean drinking water.

The Himalayan mountain range has rocks and sediments that naturally contain arsenic. As these sediments move downstream, bacteria cause arsenic to be released from the solid material into shallow aquifers.

Because relatively small amounts of arsenic wind up in rice grains grown in irrigated paddies, the authors recommend drawing from shallower wells for irrigation, reserving deep aquifers for drinking, and using filtration to remove arsenic from the water in areas without deep aquifers. The research team also recommends a vigorous, recurring testing program for wells in the region, as well as additional research into the use of rainwater harvesting and filtration.

Citation: Fendorf S, Michael HA, van Geen A.( Exit NIEHS 2010. Spatial and temporal variations of groundwater arsenic in South and Southeast Asia. Science 328(5982):1123-1127.

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New Kidney Injury Biomarker

NIEHS-supported researchers have identified a new biomarker for kidney toxicology that could lead to better and faster diagnosis of kidney injury, with potential applications in the clinical setting as well as in drug development.

Acute kidney injury, including drug-induced toxicity, is a common and often fatal clinical condition with a mortality rate of 40-80 percent in intensive care settings. Nephrotoxicity in animal studies is a major factor in the failure of many candidate drugs because of the lack of precise biomarkers for monitoring early kidney injury.

The research team tested transmembrane tubular protein kidney injury molecule -1 (Kim-1) as a superior marker for kidney injury. Traditional markers of renal injury, such as blood urea nitrogen (BUN), serum creatinine (SCr), and N-acetyl-beta D-glucosaminidase (NAG), lack the sensitivity or specificity necessary to detect nephrotoxicity before considerable loss of function occurs.

The researchers used rat toxicology studies to compare the diagnostic performance of Kim-1 to BUN, SCr, and NAG as predictors of kidney tubule damage scored by histopathology. The results show that Kim-1 outperforms all three of the other markers in multiple rat model of kidney injury. The study authors conclude that Kim-1 measurement will significantly aid the prediction of human kidney toxicity in candidate drugs by early identification and elimination of compounds that are potentially nephrotoxic.

Citation: Vaidya VS, Ozer JS, Dieterle F, Collings FB, Ramirez V, Troth S, et al.( Exit NIEHS 2010. Kidney injury molecule-1 outperforms traditional biomarkers of kidney injury in preclinical biomarker qualification studies. Nat Biotechnol 28(5):478-485.

(Jerry Phelps is a program analyst in the NIEHS Division of Extramural Research and Training.)

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