Study Links Fetal, Early Childhood Arsenic Exposure To Lung Disease

Children who are exposed to high levels of arsenic in their drinking water are seven to 12 times more likely to die of lung cancer and other lung diseases in young adulthood, according to a new study by University of California, Berkeley (UC Berkeley), and Chilean researchers.

The risk of dying due to bronchiectasis, usually a rare lung disease, is 46 times higher than normal if the child's mother also drank the arsenic-contaminated water while pregnant, according to the study. These findings, announced on March 27, provide some of the first human evidence that fetal or early childhood exposure to any toxic substance can result in markedly increased disease rates in adults.

"The extraordinary risk we found for in utero and early childhood exposure is a new scientific finding," said the study's lead author, Allan Smith, professor of epidemiology at UC Berkeley's School of Public Health. "I sometimes ponder the improbability that drinking water with concentrations of arsenic less than one-thousandth of a gram per liter could do this, and think that I've got to be wrong. But our years of working with arsenic exposure in India and Chile tie in with this study perfectly."

The paper will appear in the July print issue of Environmental Health Perspectives and was posted on its Web site March 27.

Skin, bladder and lung cancer rates are substantially higher in regions where arsenic occurs in drinking water. A recent study by Smith showed that adults exposed to arsenic can also develop decreased lung function similar to that experienced by cigarette smokers. And, in a paper to be published on April 1 in the American Journal of Epidemiology, Smith and his colleagues provide evidence that women exposed to high concentrations of arsenic during pregnancy experience six-fold increases in stillbirths and other adverse effects.

Arsenic is particularly prevalent in a province in the north of Chile and one of the driest places on earth. In 1958, the cities there of Antofagasta and neighboring Mejillones tapped into arsenic-laden rivers to supply their growing populations with water. For the next 13 years, until an expensive arsenic removal plant was installed, the water supply for all residents in the cities was laced with an average of 860 micrograms per liter of arsenic. In contrast, the standard for arsenic in drinking water in the United States was recently dropped from 50 micrograms per liter to 10 micrograms per liter, with compliance required in 2006. (A microgram is a millionth of a gram.)

With such clear-cut exposure to arsenic, the unfortunate Chilean cities became a tragic natural experiment for studying the effects of arsenic on humans.

From earlier work he and others conducted in India, Smith knew that arsenic is associated with bronchiectasis, a rare lung disease that causes distortion and dilation of the bronchi, eventually leading to chronic infections. A study involving death certificates for young adults in Antofagasta and Mejillones, Smith realized, would reveal whether lung cancer and bronchiectasis could also occur as a result of childhood exposure to arsenic.

Working with colleagues Guillermo Marshall and Catterina Ferreccio from the Pontificia Universidad Católica de Chile in Santiago, Smith compared the death rates from 1989 to 2000 of young adults in the two cities with the rates in the rest of Chile, outside of Region II. The team focused on two groups: those born between 1951 and 1958, when the water supply to the cities had relatively low arsenic concentrations, and those born during the high-exposure period of 1958 to 1971.

Both groups, they reasoned, would have been exposed to high levels of arsenic throughout some or most of their childhoods, but the second group also would have been exposed in utero, that is, while in the womb. Exposure for both groups would have abruptly declined at the same time, in 1971, when the arsenic removal plant went online.

The researchers' findings were dramatic. For people exposed to arsenic only as children, the death rate from lung cancer was seven times greater than in the rest of Chile, while the death rate from bronchiectasis was 12 times greater. For those with both early childhood and in utero exposure, the death rate from lung cancer was six times greater than that in the rest of Chile, and the death rate from bronchiectasis was an astonishing 46 times greater.

In absolute numbers, there were nine deaths from bronchiectasis, 16 from lung cancer and seven from other lung diseases in adults aged 30 to 49 who were born during the period of high exposure. In the year 2000, there were about 300,000 people living in the two cities where the study was conducted.

"In all my career, these are the most amazing findings I've confronted so far," Smith says. "Their magnitude is unparalleled. Not only are these the highest death rates for lung cancer and bronchiectasis ever discovered among young adults, but they are also the strongest evidence I know of to date that implicates not just arsenic, but any environmental exposure in utero or in early childhood to any adverse health effect in adults."

Putting these results in perspective, studies have found that the rates of early-adult lung cancer among survivors of the atomic bombings at Hiroshima and Nagasaki who were exposed to high levels of radiation before birth or as children are many times lower than those in Antofagasta and Mejillones, as are the rates among young adults exposed to secondhand tobacco smoke as children. Only active smoking itself results in lung cancer rates higher than the seven-fold increase found in his study, Smith said.

The work was conducted by the Arsenic Health Effects Research Program at UC Berkeley's School of Public Health and funded by the National Institute of Environmental Health Sciences, one of the National Institutes of Health. Other researchers who worked on the study are Yan Yuan, Jane Liaw, Ondine von Ehrenstein and Craig Steinmaus, all with the Arsenic Health Effects Research Program.

The paper, "Increased Mortality from Lung Cancer and Bronchiectasis in Young Adults Following Exposure to Arsenic In Utero and Early Childhood," is available online at

Allan Smith:

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