AWWA: As-Related Cancer, Mortality, Derm Changes RFPs

Gary Greenberg Gary.Greenberg at Duke.edu
Mon Jan 29 05:51:29 EST 2001

American Water Works Association Research Foundation (AwwaRF) Solicited
(303) 347-6244
AWWA Research Foundation
6666 West Quincy Avenue
Denver, Colorado 80235

fblaha at awwarf.com





Determine the correlation of arsenic in drinking water with human
mortality in at least three geographic regions in the United States.


Epidemiological studies in Taiwan, Chile and Argentina demonstrate an
association between high levels of arsenic and drinking water and
various cancers. Engel and Smith published an ecological mortality study
in the U.S. on the effect of arsenic on vascular disease in 1994 that
demonstrated an association (1.9 and 1.6 standard mortality ratio for
men and women respectively) with disease of arteries, arterioles, and
capillaries. In 1998 the United States Environmental Protection Agency
(USEPA) performed a cohort mortality study on arsenic in drinking water
in Utah. The results of the study were essentially negative, although
there was an association with prostate cancer and cardiovascular
disease. However, this association may have been a statistical artifact.
Nonetheless, the Utah study demonstrated that an epidemiological
mortality study can be completed in the United States with statistically
significant results. Some experts consider the results of the Utah study
controversial because the individuals in the population studied were
members of the Church of Latter Day Saints. While the lifestyle of this
population eliminates some of the most common confounding factors in
cancer epidemiological studies (smoking, alcohol and caffeine
consumption), some feel that it is not representative of the U.S.
population as a whole. Other communities with higher levels of arsenic
in household wells exist in other parts of the country, including
California, Maine, Minnesota, Nebraska, Nevada, New Hampshire, New
Mexico, Washington and Wisconsin. More work is needed to determine
whether arsenic in drinking water contributes to mortality in the United



(RFP 2738)


Compare and correlate arsenic levels in drinking water with cancer
incidence in populations, using cancer registries in the United States.
Develop data to help refine the dose-response relationship between
arsenic exposure from drinking water and cancer of the skin, bladder,
and lung, and other cancers.


The Safe Drinking Water Act (SDWA) mandates that the USEPA be
responsible for identifying and regulating contaminants with known
adverse health effects, such as arsenic, in public drinking water
supplies. In 1975, the USEPA adopted an interim drinking water standard
or maximum contaminant level (MCL) of 50 mg/L for arsenic. This level
had been developed by the Public Health Service in 1942 based on
information about arsenic’s acute poisonous effects. Revision of the MCL
is underway and a final standard must be promulgated by June 2001. A key
question for regulatory purposes is whether the current standard poses
an unacceptable health risk. There is a need to establish a
dose-response relationship to help determine whether the current
standard is adequate.

EPA has identified arsenic as a group A “known” human carcinogen. The
classification is based on evidence of carcinogenicity from human data
involving occupational and drinking water exposures, including the Tseng
et al. (1968) epidemiological study in Taiwan. Several other
epidemiological studies on arsenic in drinking water have been completed
in other countries including Taiwan, Argentina and Chile. The studies
have looked at cancer incidence and mortality rates and different
arsenic exposure levels.

AwwaRF’s Feasibility of New Epidemiologic Studies of Low Level Arsenic
(1999) identified two different epidemiological studies of arsenic at
low levels of exposure in drinking water. The studies included a
population-based case-control study to assess the dose-response
relationship between bladder cancer and low level arsenic in drinking
water in three counties in the United States, and a study of skin
lesions in West Bengal, India. The West Bengal study was also to explore
factors, such as diet and methylation efficiency, that may lead to
variability in health responses to arsenic. The National Institute of
Environmental Health Services and the United States Environmental
Protection Agency /U.S. State Department funded the American and Indian
studies, respectively.

Lewis et al. (1999) published a cohort mortality study in Utah that
showed some correlation with cardiovascular effects and prostate cancer,
however, some experts believe these correlations are coincidental and
not indicative of a cause-and-effect relationship. Other experts believe
that the Utah study is not representative of the general population in
the United States. This study could help resolve some of the controversy
associated with the Utah study.

Although epidemiological studies have clearly shown a causal
relationship for increased cancer risks in individuals having exposures
to high levels of arsenic in drinking water outside of the United
States, further development of data is needed on several types of
internal cancers that have been associated with arsenic exposure.
Epidemiological studies are needed to characterize the dose-response
relationship for arsenic associated cancer endpoints especially at low
doses and in United States populations.

Research Approach

The objective of this research is to determine the correlation of
arsenic in drinking water with cancer in populations in at least three
geographic regions in the United States. The proposer may consider using
previously established arsenic occurrence databases from the American
Water Works Association, the USEPA, Office of Groundwater and Drinking
Water Targeting and Analysis Branch (25-state arsenic database), and the
U.S. Geological Survey. In the proposal the proposer will identify and
justify the following:

· Arsenic occurrence database(s) and method of estimating exposure;

· Cancer registries and method of measuring incidence;

· Reason for selection of geographic regions;

· Statistical method(s) for correlation of arsenic exposure to cancer

· Potential sources of bias, including selection bias, information bias,
and confounding bias;


· A strategy to mitigate bias and confounding factors.

Access to the appropriate databases should be supported by a letter from
the database manager that is included as an Appendix to the proposal.

The final report will detail the approach, confounding and modifying
factors, and statistical analysis of the study. In addition, the report
will discuss the correlation between drinking water arsenic exposure and
cancer incidence. The report will be presented in such a way to help
improve the scientific drinking water community’s quantitative and
qualitative understanding of adverse human health effects of arsenic in
drinking water. The outcome will provide a dose response analysis, not a





Determine the feasibility of a study on the correlation of populations
exposed to arsenic in drinking water in the United States and
dermatological changes.


Hyperkeratoses on the palms of the hands and soles of the feet and
hyper- and hypo-pigmentation on the trunk of the body and extremities
are indicative of arsenic toxicity. Epidemiological work has identified
these dermatological changes to be associated with arsenic exposure in
Argentina, China, Taiwan, Bangladesh, India, and Chile. There is some
evidence that these skin changes are a particularly sensitive marker of
arsenic exposure. A recent study conducted by the USEPA and the
University of New Mexico determined that dermatologists can recognize
arsenic-induced skin changes and have seen such cases in their practices
in the Southwest United States. Thus, it may be possible to conduct
population-based U.S. studies and to determine whether specific skin
changes are associated with the relatively low levels of arsenic
exposure experienced in the U.S.

Research Approach

The researcher will assess the feasibility and value of conducting at
least one study on the correlation of arsenic-induced dermatological
changes with arsenic in drinking water. Multiple populations of varying
ranges of exposure and various geographical areas should be considered.
The researcher will focus on exposures from 5 to 100 mg/L. Further, a
detailed design plan for the most favorable assessment should be
developed. To achieve this the researcher should conduct the following

1. Define the criteria for identifying candidate populations where
studies on arsenic-induced dermatological changes in water may be
conducted, e.g., current exposure, manifestations of arsenic toxicity.

2. Identify U.S. populations that meet the above criteria.

3. Determine the protocol for evaluating dermatological changes due to

4. Determine alternative study approaches and the logistical needs for
each approach, e.g., measurements of exposure, use of local people for
support tasks, political climate.

5. Determine and compare the feasibility of conducting the identified

6. Develop a detailed design plan for the study that demonstrates the
greatest potential of a statistically valid and robust epidemiological
study on the correlation of arsenic in drinking water with
dermatological changes. This plan should be fully developed and its
scientific merit thoroughly assessed according to the recommended study
criteria. The researcher is required to submit a written report to the
Research Foundation. The report should include a rank order and a
summary of the feasibilities of the identified epidemiologic study(ies)
as well as the detailed design plan developed to complete task #6. The
reported feasibility assessments should describe the strengths and
weaknesses of each study approach, the pros and cons of using the
identified population centers, and the utility of the study results.
Estimated time frames and costs in U.S. dollars for each study should be
included in the final report.

Gary N. Greenberg, MD MPH    Sysop / Moderator Occ-Env-Med-L MailList
gary.greenberg at duke.edu     Duke Occupat, Environ, Int & Fam Medicine
OEM-L Maillist Website:                      http://occhealthnews.com


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