EPA/600/A-92/153
U.S. ENVIRONMENTAL PROTECTION AGENCY
HEALTH EFFECTS RESEARCH
ON DRINKING WATER CONTAMINANTS
Fred S. Hauchman
Associate Director for Water
Health Effects Research Laboratory
U.S. Environmental Protection Agency
Research Triangle Park, NC 27711
INTRODUCTION
The Safe Drinking Water Act of 1974 (SDWA), as amended in 1986,
provides a mandate to the U.S. Environmental Protection Agency (EPA) to
ensure the safety of the nation's drinking water. The SDWA requires that most
public water supplies use filtration and/or disinfection to prevent waterborne
infectious disease. Chemical and microbial contaminants on the Drinking Water
Priority List are regulated in phases every three years. For each contaminant
that is regulated, the EPA must establish Maximum Contaminant Level Goals
(MCLGs) and Maximum Contaminant Levels (MCLs). MCLGs are non-
enforceable health-based standards that represent water treatment goals. MCLs
are enforceable standards based on health concerns plus a consideration of risk
management factors such as the technological feasibility of controls, the
availability of analytical techniques, and the economic impact of the regulation.
For chemicals that may enter drinking water by accident, risk assessment-based
health advisories (HAs) are developed. HAs are concentrations of a
contaminant that are not expected to cause adverse noncancer health effects after
exposures varying from one day to a lifetime.
The development of these requirements depends in part upon the ability of
EPA to comprehensively assess the risks associated with exposure to chemical
and microbial contaminants for the various water treatment options. The EPA
Office of Research and Development (ORD) conducts research that forms the
scientific basis for this comparative assessment, and provides data and methods
that are used by the EPA Office of Water in the development of regulations
required by the SDWA. This research is conducted within the context of the
various components of the National Academy of Sciences risk assessment
paradigm1: hazard identification, dose-response assessment, exposure
assessment, and risk characterization.
Several ORD laboratories and offices are involved in drinking water
research and assessment activities. These include the Health Effects Research
Laboratory (HERL) in Research Triangle Park, North Carolina, and the
Environmental Monitoring Systems Laboratory, the Environmental Criteria and
Assessment Office, and the Risk Reduction Engineering Laboratory in
Cincinnati, Ohio. This paper briefly discusses drinking water health research

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needs, and then focuses on the health effects research program at HERL. It
should be pointed out that several health-related research projects, such as the
study of waterborne pathogens and the development of risk assessment methods,
involve multi-laboratory/office collaboration within EPA.
HEALTH RESEARCH NEEDS
Health effects concerns for drinking water generally fall within the
following areas:
1)	The chemical and microbiological quality of source waters. Chemical
contaminants of concern in source waters include substances such as arsenic,
pesticides in agricultural areas, and solvents from underground injection of
wastes. Source water microbial contaminants include pathogens such as
Cryptosporidium. Giardia, and waterborne enteric viruses (e.g., Norwalk virus).
2)	The safety of the disinfection process. Disinfection of drinking water
with chlorine has been the conventional treatment of choice for protecting the
public against waterborne microbial disease. Public health concern over the
safety of the disinfection process is based on the recognition that chlorination
and alternative disinfectant treatments produce a wide variety of by-products,
many of which have been shown under experimental conditions to cause cancer
and other toxic effects. Drinking water requirements must therefore minimize
the risk associated with exposure to the most toxic chemical contaminants, while
protecting against microbial contamination.
3)	The impact of nondisinfectant chemical additives. These include
clarifying agents such as alum that are used to remove suspended particulate
matter in source water, and other substances that are added to adjust such
characteristics as pH and water hardness.
4)	The safety of distribution system contaminants. Toxic chemicals such as
copper, lead, and other metals may leach into the drinking water as it passes
through the distribution system. Microbial concerns relate to the growth/
regrowth of pathogens in the distribution system.
The list of health research needs for drinking water contaminants is
extensive, particularly for certain microbes and chemicals found in source waters
and for the chemical by-products of disinfection. The toxic effects of many
chemical contaminants are unknown or poorly characterized. This is particularly
true for the by-products of ozonation. Beyond the need for basic toxicological
data, an improved understanding of the chemical, physical and biological
processes involved in toxic responses is critical to evaluating the human risk
associated with exposure to these contaminants. Studies are needed to evaluate
the toxicity of the complex mixture of contaminants to which human
populations are exposed. For microbes, there is considerable uncertainty with
regard to the infectious dose for high priority waterborne pathogens, the

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influence of host factors (e.g., immune status) on infectivity and pathogenicity in
humans, and the occurrence of endemic microbial disease in populations
consuming water that meets existing treatment standards.
EPA DRINKING WATER HEALTH RESEARCH
Priorities for selecting health effects research projects on drinking water
contaminants are based on a consideration of several criteria: the potential
regulatory and public health impact of a research issue; the ability to lead to a
major scientific improvement in a drinking water risk assessment; the likelihood
of significant progress within a 3-5 year time frame; and the ability to extend
results to other drinking water scientific issues. Resources for drinking water
health research at EPA have gradually declined since the mid-1980's. Due to
resource constraints, research in a number of high priority areas is either
nonexistent or inadequate.
The primary emphasis of the program is on key disinfection by-products
and source water contaminants. An integrated research program has been
developed at EPA in three major areas: toxicology, pharmacokinetics, and
human studies. A brief description of the research in each of these areas is
found below.
Toxicology
Cancer. The drinking water regulatory program requires quantitative
estimates of cancer risk (e.g., for the development of MCLs) for carcinogens of
concern. The rodent cancer bioassay program at HERL addresses this need by
providing data on cancer potency as well as mechanisms of action for key
disinfection by-products. Hie long-term research goal is the development of
biologically-based models to improve the scientific basis for risk assessment.
The list of chemicals selected for study reflects the regulatory priorities of
the Office of Water. Chemicals for which studies are either ongoing or planned
include bromodichloromethane, di- and trichloroacetic acid, chloral hydrate,
bromate, and the brominated acetic acids. By-products of ozonation have been
given the highest priority due to the anticipated increase in use of this
disinfection practice and the critical need for toxicologic information on these
substances. An additional feature of the chronic bioassay program is that it
provides opportunities for collaborative research across disciplines at HERL.
Animals exposed to the various disinfection by-products are being used for
parallel studies in pharmacokinetics, neurotoxicology, reproductive toxicology,
immunotoxicology, and genetic toxicology.
Genotoxicity. This research involves the application of short-term in vitro
tests for genotoxicity (e.g., mutagenicity assays in Salmonella), in combination
with chemical fractionation, to study the complex mixtures of by-products in
water subjected to different treatment processes. Studies are also underway to

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characterize the genotoxicity of complex mixtures of by-products at the
molecular level. The overall goal is to identify toxic species within mixtures so
that control technologies can be developed to reduce or eliminate them from
potable water.
Reproductive and Developmental Toxicity. Studies are underway to
evaluate the developmental and reproductive toxicity of high priority
disinfection by-products. The long-term goal of this research is to evaluate the
sensitivity of reproductive measures to assess the risk of key disinfection by-
products. Acute and subchronic tests in rodents are underway to evaluate the
male reproductive toxicity of the brominated acetic acids. Reproductive
endpoints are also being evaluated in animals exposed to dichloroacetic acid and
chloral hydrate in the cancer bioassay program.
Neurotoxicity. Research is being conducted to evaluate the potential
neurotoxic effects of selected disinfection by-products. Current studies involve
qualitative and quantitative assessments of the neurotoxicity of dichloroacetic
acid. A battery of tests is being developed for rapid hazard identification of
developmental neurotoxicants found in drinking water. In addition, a short-term
test is being developed to assess the potential neurotoxicity of chemicals in
drinking water.
Research on aluminum, a widely used clarifying agent in water treatment
processes, is being conducted to address concerns that this metal may be
associated with neurodegenerative disorders in highly susceptible populations
such as the elderly. The toxicity of aluminum to the nervous system is well-
established; however, whether neurotoxicity may arise from the levels and routes
of exposure that occur in the environment is a controversial and inadequately
studied issue. The goal of this research is to provide a qualitative and
quantitative assessment of the risks associated with exposure to aluminum in
drinking water, using a homologous model of learning and memory in humans
and animals.
Pharmacokinetics
Pharmacokinetic research determines the relationship between the applied or
environmental exposure level of a chemical agent and the dose of the chemical
or its metabolite at a target site in the body. Studies of chemical uptake,
distribution and metabolism in rodents are being conducted to facilitate the
extrapolation of effects from animals to humans and from high to low dose
levels. These studies are being complemented by toxicity studies (hepatotoxicity
and renal toxicity in particular) and by chemical reactivity studies that include
structure/activity analyses. Research is being conducted on the trihalomethanes
and the haloacids, with a primary focus on bromodichloromethane. The goal of
this program is to develop physiologically-based pharmacokinetic models, to be
used in combination with biologically-based dose-response models, for the most
important disinfection by-products of regulatory concern.

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Research on arsenic is addressing several key scientific issues that impact
the risk assessment for this important source contaminant. The goal of this
research is to provide a better understanding of the dose-response relationship
for arsenic toxicity, the relationship of metabolism to toxicity, and other
important factors that can affect sensitivity (susceptible subgroups). These
studies will make significant improvements to the risk assessment for arsenic
and will also provide information of general utility in understanding mechanisms
of chemical carcinogenicity.
Human Studies
The epidemiologic research program at HERL assesses the possible changes
in morbidity and mortality linked to the consumption of treated water. HERL is
evaluating the feasibility of conducting epidemiologic studies of populations
consuming water that is treated with chloramines or with ozone. Another
feasibility study involves an assessment of the risk to communities served by
water contaminated with arsenic. A number of infectious disease
epidemiology/clinical studies are planned in collaboration with the EPA
Environmental Monitoring Systems Laboratory and other groups inside and
outside of EPA. Possible activities include an epidemiologic study of endemic
waterborne infectious disease, clinical dose-response studies of waterborne
pathogens (e.g., Cryptosporidium), and a waterborne disease outbreak and
reporting project.
SUMMARY
Three critical and interrelated research needs for drinking water are to
identify the chemical and microbial contaminants of greatest public health
concern, to relate the toxic effects observed experimentally in animals to
potential effects in humans, and to determine the actual risks associated with
human exposure to these contaminants in drinking water. Health effects
research at EPA to address these needs can be described within the context of
the four components of the risk assessment process; hazard identification, dose-
response assessment, exposure assessment, and risk characterization.
To determine the chemicals and microbes of greatest public health concern,
EPA conducts hazard identification and dose-response research in animals and
humans. Such studies help to characterize the toxic endpoints of concern and
the exposure levels at which these effects occur. In vitro studies and
structure/activity analyses are useful screening tools to provide additional
information about the potential toxicity of contaminants of concern.
EPA research to facilitate the extrapolation of toxicity data from animals to
humans involves pharmacokinetic studies and studies to determine the biological
mechanism by which toxic agents cause their effects. This type of research
leads to the development of biologically-based dose-response models for use in
risk assessment. The use of these models for specific chemical contaminants

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represents a significant improvement over the conventional approach that
generally relies upon a number of conservative default assumptions.
Finally, characterization of the risks associated with human exposure to
contaminants in drinking water involves incorporating the results of the research
described above, in combination with environmental exposure data, into
chemical and microbial risk models. The many uncertainties in the underlying
health effects data base and in the models used for assessing chemical and
microbial risks highlight the need for a strong drinking water health research
program in the years to come.
REFERENCE
1.
National Academy of Sciences, 1983. "Risk Assessment in the Federal
Government: Managing the Process", National Academy Press,
Washington, D.C.

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1. REPORT NO. 2.
EPA/600/A-92/153
3.
4. TITLE ANDSUBTITLE
U. S. Environmental Protection Agency
Health Effects Research on Drinking Water
Contaminants
5. REPORT DATE
6. PERFORMING ORGANIZATION CODE
7. AUTHOR(S)
Fred S. Hauchman
8. PERFORMING ORGANIZATION REPORT NO.
9. PERFORMING ORGANIZATION NAME AND ADDRESS
Health Effects Research Laboratory
Office of Research and Development
U. S. Environmental Protection Agency
Research Triangle Park, NC
10. PROGRAM ELEMENT NO.
11. CONTRACT/GRANT NO.
12. SPONSORING AGENCY NAME AND ADDRESS
L). S. Environmental Protection Agency
Health Effects Research Laboratory
MD-51A
Research Triangle Park, NC 27711
13. TYPE OF REPORT AND PERIOD COVERED
14. SPONSORING AGENCY CODE
EPA/600/10
tS, SUPPLEMENTARY NOTES
16. ABSTRACT
The Environmental Protection Agency's (EPA) Health Effects Research Laboratory
(HERL) provides chemical-specific data and scientific methods that are used by the
EPA Office of Water in the development of regulations required by the Safe Drinking
Water Act. To determine the chemical and microbial contaminants in drinking water
that are of greatest public health concern, HERL conducts hazard identification and
dose-response, research in humans, animals, and in vitro. HERL conducts studies on
pharmacokinetics and mechanisms of action to faci/litate Jpe extrapolation of toxicity
data from animals to humans. Characterization of the risks associated with human
exposure to contaminants in drinking water invedves a multi-laboratory/office effort tjo
incorporate information on hazard, dose-response, and exposure into chemical and
microbial risk models. The many uncertainties in the underlying health effects data
base and in the models used for assessing chemical and microbial risks highlight the
need for a strong drinking water health research program in the years to come. -
17. KEY WORDS AND DOCUMENT ANALYSIS
a. DESCRIPTORS
b. IDENTIFIERS/OPEN ENDED TERMS
c, cosati field/Group



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