Arsenic Exposure's Carcinogenic Effects Are Delayed but Linger

BERKELEY, Calif., June 14 -- Arsenic exposure increases the risks of bladder and lung cancer a decade after exposure, according to researchers here.

In a region of Chile where drinking water became highly contaminated with arsenic, lung and bladder cancer deaths began to rise 10 years after exposure began and remained high for 25 years after it ended, found Allan H. Smith, M.D., Ph.D., of the University of California at Berkeley, and colleagues.

At the peak, 10 to 20 years after exposure began, lung cancer deaths were threefold higher and bladder cancer deaths six to 14 times higher than in a control region, they reported online in the Journal of the National Cancer Institute.

"The impact of arsenic in drinking water on this large population is without precedent for environmental causes of human cancer, and it points to the public health priority of ensuring that arsenic concentrations in drinking water are controlled worldwide," the researchers said.

They added, "Latency patterns are usually difficult to obtain for human cancers. Rate ratio estimates of this size for a defined large population living in a region of a country are, we believe, without precedent for any cause of any human cancer."

The study monitored cancer mortality over a 50-year period that saw a sharp rise and fall of arsenic levels in the area's drinking water.

In Chile's arid region II, drinking water was obtained almost exclusively through municipal water systems supplied by rivers originating in the Andes mountains.

Before 1958, the arsenic concentration in the water of the region's major city, Antofagasta, was about 90 ?g/L. The drinking water standard in the United States at the time was 50 ?g/L and dropped to 10 ?g/L in 2006.

But in 1958, water from two rivers containing high levels of arsenic was used to supplement the municipal supply. Arsenic concentrations rose to an average of 870 ?g/L for two of the largest cities in the region.

Then in 1971, a water treatment plant was installed in Antofagasta and other cities and towns followed suit, leading to substantially lower arsenic concentrations. Average arsenic concentrations for the entire region fell to 272 ?g/L from 1970 to 1974 and by 1990 were down to 43 ?g/L.

Another region with low water arsenic concentrations (0.5 to 1.1 ?g/L in 1998) was used as the comparator.

The population exposed included 251,976 residents of region II in 1970. In the follow up period from 1950 to 2000 there were 3,406 lung cancer deaths and 726 bladder cancer deaths in the region.

Mortality causes were followed using death certificates and mortality data from the Chile National Institute of Statistics and Chile's Ministry of Health.

Cancer mortality risk began to rise between 1968 and 1978 -- 10 to 20 years after high exposures began.

Among the findings comparing the two regions, the researchers reported:

• Lung cancer deaths peaked among men from 1992 to 1994 (rate ratio 3.61 (95% confidence interval 3.13 to 4.16).
• Lung cancer deaths peaked among women from 1989 to 1991 (RR 3.26, 95% CI 2.50 to 4.23).
• Bladder cancer deaths peaked among men from 1986 to 1988 (RR 6.10, 95% CI 3.97 to 9.39).
• Bladder cancer deaths peaked among women from 1992 to 1994 (RR 13.8, 95% CI 7.74 to 24.5).

Mortality rates were highest in the region with contaminated water from 1992 to 1994 -- more than 20 years after exposure ended -- at 130 per 100,000 persons per year for lung cancer and 23 per 100,000 persons per year for bladder cancer.

In contrast, the control region had only 47 lung cancer deaths per 100,000 persons per year and seven per 100,000 persons per year during the same period.

The elevated risk for those living in the region with contaminated water began to drop off after 1990, though bladder cancer among women peaked a few years later.

The lung cancer effect was greatest among men who would have been exposed to high arsenic levels as young children (the birth cohort from 1938 to 1957). No difference was seen between women exposed as children, as young adults, or as older adults.

The study was unique in that it included the largest number of cancer deaths of any arsenic study and had a well-defined population and well-documented exposure, the researchers said.

Though smoking also causes lung and bladder cancers, it could not have been responsible for the increased mortality because smoking rates were not different between regions and the observed risk was greater than that from smoking.

The study was limited by lack of individual data on arsenic exposure and other risk factors, such as smoking. It also did not account for migration between regions of the country, though the annual internal migration rate from 1965 to 2000 was only 0.6%.

Other regions of the world have populations at risk as well, noted Jay H. Lubin, Ph.D., of the National Cancer Institute in Rockville, Md., and colleagues, in an accompanying editorial.

In the United States, water systems serving about 13 million people have arsenic concentrations exceeding 10 ?g/L. Levels exceed 50 ?g/L in some areas of California, Nevada, Alaska, Michigan, New England, New Mexico, and Utah.

Other affected countries with affected areas include Bangladesh (with an estimated 25 million people exposed to concentrations above 50 ?g/L), India (an estimated six million in West Bengal), Argentina, Inner Mongolia, China, Finland, and Mexico.

"With large numbers of people potentially exposed to arsenic in drinking water above 10 ?g/L, the full scope of the public health consequences of arsenic in drinking water is not yet clear," Dr. Lubin and colleagues concluded.