Arsenic could be toxic at much lower levels than previously thought

Arsenic could be toxic at much lower levels than previously thought, suggesting that the new EPA drinking water standard of 10 parts per billion might still be too high, according to a team of researchers at Dartmouth Medical School.

The study, which appears in the August 2004 edition of Chemical Research in Toxicology, shows that in cell cultures extremely low levels of arsenic act as an endocrine disruptor. Endocrine disruption is likely to be an important contributor to arsenic’s ability to increase risk of a host of diseases including several forms of cancer, heart disease, diabetes, and reproductive or developmental problems.

New medical research on arsenic, long recognized as a fatal poison when administered in high doses, indicates that decades of exposure to low doses of arsenic can pose a significant threat to human health. People are primarily exposed to arsenic through drinking water, which is contaminated naturally by underground geological sources in some areas of the world. In 2001, the U.S. Environmental Protection Agency adopted a new standard for arsenic in drinking water at 10 parts per billion (ppb), replacing the old standard of 50 ppb. Public water systems must comply by 2006.

The new standard, however, might still be too close to arsenic levels related to known health effects to offer a protective margin for most members of the public, says Joshua Hamilton, PhD, professor of pharmacology and toxicology at Dartmouth Medical School and one of the authors of the new study. The research team includes lead author and Research Associate Professor of Physiology Jack Bodwell, PhD, and Lauren Kingsley, who was a Dartmouth undergraduate when the work was done.

By examining the effects of arsenic on a rat cell line, Hamilton and his colleagues confirmed their earlier report that arsenic can act as an endocrine disruptor, while also finding that these toxic effects occur at extremely small concentrations — as low as 20 times below the new standard of 10 ppb. Endocrine-disrupting chemicals disturb hormone signaling and regulation in the body, causing reproductive problems and other abnormalities.

“I would hope that the arsenic drinking water standard could be revisited,” Hamilton says, suggesting that a standard of 2-3 ppb would provide a more substantial margin protective of public health. This is supported by several recent epidemiological studies that have found subtle health effects at as low as 10 ppb.

“Opponents say that there is no concrete evidence that there is a health benefit from further lowering of the standard,” Hamilton says, “but this is one of the few — perhaps the only — drinking water standards where there are measurable health effects at or so close to the Federal Maximum Contaminant Level.”

The researchers examined the effects of arsenic on the glucocorticoid receptor (GR), which is involved in many important body processes, such as regulating blood sugar and vascular function, and suppressing skin and lung cancer. Interestingly, the primary effects of arsenic exposure in humans are increased risk of diabetes, vascular disease, and skin and lung cancer, according to DMS investigators.

They also found that arsenic affects cells differently, depending on the amount of GR in the cell. “Different tissues and organs of our body naturally have different levels of GR,” Hamilton explains. “This may lead to different arsenic responses, which may in turn lead to different effects in different tissues.”

“Such variations in response may account for why arsenic exposure has been linked to certain diseases, but it also predicts that different levels of arsenic may have very different effects,” he continues. “So we may see an entirely different pattern of diseases at very high doses, such as in Bangladesh or Taiwan, than at lower doses such as those in the United States and South America.”

Hamilton and his DMS colleagues are currently researching endocrine disruption in animals and humans to further explore the arsenic’s impact on human health, which they hope to publish later this year. Hamilton is a member of the Epidemiology and Chemoprevention Research Program of the Norris Cotton Cancer Center.