United States Office of Water EPA 815-R-00-015

Environmental Protection (4607) December 2000

Agency Washington, DC 20460 www.epa.gov/safewater

Report to Congress

EPA Studies on Sensitive

Subpopulations 

and 

Drinking Water Contaminants
i

EXECUTIVE SUMMARY

The Safe Drinking Water Act (SDWA) requires the U.S. Environmental Protection

Agency (EPA) to establish national drinking water standards that protect the health of the 250

million people who get their water from public water systems. These standards are intended to

protect the general public as well as those groups of individuals who may be more sensitive than

the general population to the harmful effects of contaminants in drinking water. The high priority

assigned to studies of sensitive subpopulations and to the drinking water research program in

general reflects the Agency’s commitment to ensuring that regulatory decisions on

microbiological and chemical contaminants in drinking water have a strong scientific foundation

for public health protection. 

The 1996 SDWA Amendments (Section 1458(a)) include the following requirements for

conducting studies on sensitive subpopulations:

(1) The Administrator shall conduct a continuing program of studies to identify

groups within the general population that may be at greater risk than the general

population of adverse health effects from exposure to contaminants in drinking water. The

studies shall examine whether and to what degree infants, children, pregnant women, the

elderly, individuals with a history of serious illness, or other subpopulations that can be

identified and characterized are likely to experience elevated health risks, including risks of

cancer, from contaminants in drinking water. 

(2) Not later than 4 years after the date of enactment of this subsection, and

periodically thereafter as new and significant information becomes available, the

Administrator shall report to the Congress on the results of the studies.

This document is the first Report to Congress on the status, results and future directions

of studies conducted by the EPA to identify and characterize sensitive subpopulations that may be

at greater risk from exposure to drinking water contaminants than the general population. 

Sensitive subpopulations are defined in this report as groups of individuals who respond

biologically at lower levels of exposure to a contaminant in drinking water or who have more

serious health consequences than the general population. EPA is conducting a program of studies

to identify such groups -- which may include infants, children, pregnant women, the elderly, or

individuals with a history of chronic illness -- and to evaluate whether and to what degree they are

likely to experience elevated health risks.

The studies conducted or supported by EPA have been guided by the Agency’s research

plans and strategies, expert workshops on special topics, and consultations with other agencies,

research organizations, and the drinking water community. Partnerships with Federal agencies,

the water industry, universities and other research entities have been essential to the successful

implementation of the Agency’s program to address this issue. EPA studies of sensitive

subpopulations involve multidisciplinary research and assessments to identify the scope of possible
ii

health outcomes, including cancer, reproductive toxicity, gastrointestinal illness, and other

adverse health effects. Approaches being used to address sensitive subpopulation issues include:

! Population-based epidemiology studies to identify potentially harmful contaminants,

risk factors and sensitive subpopulations; 

! Clinical studies to evaluate the effects of specific contaminants and the host factors

that influence the disease process;

! Studies in laboratory animals to provide hazard identification and dose-response

data, as well as to elucidate how contaminants cause their effects;

! The development and validation of standardized test methods for the evaluation of

contaminants that may be of special concern to certain subpopulations;

! The development of improved methods and data bases to better estimate total

exposures to drinking water contaminants from all relevant sources and routes (i.e.,

oral, dermal and inhalation);

! The compilation of existing data to assist in characterizing specific sensitive

subpopulations; and

! The development of improved risk assessment methods that will permit better use of

all available information on health effects and exposure.

Important factors that are being investigated include life stage (i.e., fetuses, infants and

children, the elderly), gender, genetic traits, health status and exposure. Research has focused on

the highest priority waterborne pathogens and chemicals from a public health and regulatory

perspective. The parasite Cryptosporidium, for example, has been reported to be the cause of

over 14 outbreaks in the U.S. since 1985, including one in Milwaukee in 1993 that involved an

estimated 400,000 illnesses and over 50 deaths. A large number of these deaths occurred in

individuals with weakened immune systems. Data from the laboratory and field suggest that

exposure to disinfection by-products (DBPs), which are formed when chlorine and other

disinfectants react with naturally occurring materials in the water, may pose a risk of certain types

of adverse health effects. The 1996 SDWA Amendments specifically identify these and several

other contaminants as high priorities for research and regulatory determinations.

Highlights from the EPA program of studies on sensitive subpopulations are described

below:

Waterborne pathogens. The results of an analysis of physiological and exposure-related

characteristics of infants and children suggest that these groups may be more sensitive than the

general population to waterborne pathogens. This is consistent with data collected on the

demographics of foodborne illnesses, but the data from waterborne disease outbreaks in the U.S.

are less conclusive. The results of several epidemiology studies and surveys that are currently

underway should provide important information on the risks that pathogens in drinking water

pose to infants, children, and other age groups. Individuals with pre-existing disease, particularly

those with weakened immune systems, are known to be at increased risk following exposure to
iii

opportunistic pathogens such as Cryptosporidium. EPA is conducting research in the laboratory

and field to further evaluate the impact of host immune status on sensitivity to these agents.

Chemicals. Studies conducted by EPA and others have raised concerns about a potential

risk of adverse reproductive outcomes following maternal exposure to DBPs. EPA research has

also shown that exposure of laboratory animals to high levels of certain pesticides can cause

adverse developmental effects. Current laboratory research on pesticide modes of action, along

with epidemiology studies of childhood sensitivity to pesticides, will contribute to a better

understanding of the potential risks of these contaminants to subpopulations of special concern. 

In studies to evaluate the health effects of sulfate, EPA researchers and collaborators found that

piglets (as a model for human infants) and previously unexposed adults were not particularly

sensitive to the effects of this contaminant in drinking water. 

Considerable progress has been made in the development of improved methods for

evaluating toxicity, assessing exposures, and conducting risk assessments of contaminants and

subpopulations of special concern. These new tools will enable Agency scientists to generate

critical data and conduct scientifically sound risk assessments in support of the requirements of

SDWA and other regulatory statutes.

Future priorities include studies of DBP exposures and adverse reproductive outcomes,

risks to infants and children from exposure to waterborne pathogens, and risks to individuals

whose health status is compromised. The Agency will continue to support studies that further

characterize risks to the elderly and that evaluate the role of genetic factors in environmentallyinduced disease. Emphasis will also be placed on the development of improved methods for

assessing toxicity, exposure and risk.
iv

CONTRIBUTORS

Principal Author: Fred Hauchman, Office of Research and Development

Steering Committee: Joyce Donohue, Office of Water

Ken Elstein, Office of Research and Development

Karl Jensen, Office of Research and Development

Amal Mahfouz, Office of Water

Dan Olson, Office of Water

Robin Oshiro, Office of Water

Sherri Umanski, Office of Water
v

TABLE OF CONTENTS

EXECUTIVE SUMMARY .................................................... i

CONTRIBUTORS ......................................................... iv

1. INTRODUCTION ..................................................... 1

2. BACKGROUND ...................................................... 2

2.1 Definition of Sensitive Subpopulations ................................ 2

2.1.1 Intrinsic Factors ........................................... 3

2.1.2 Acquired Factors .......................................... 4

2.2 Contaminants of Concern .......................................... 4

2.2.1 Waterborne Pathogens ...................................... 4

2.2.2 Chemicals ................................................ 6

3. OVERVIEW OF RESEARCH PROGRAM .................................. 7

3.1 Risk Assessment Framework ....................................... 7

3.2 Identification and Prioritization of Research Needs ....................... 7

3.3 Research Approach .............................................. 8

4. EPA STUDIES ON SENSITIVE SUBPOPULATIONS ........................ 9

4.1 Life Stages ..................................................... 9

4.1.1 Fetuses .................................................. 9

4.1.2 Infants and Children ....................................... 11

4.1.3 The Elderly .............................................. 13

4.2 Gender ....................................................... 13

4.3 Genetic Traits .................................................. 14

4.4 Health Status .................................................. 16

4.5 Exposure ..................................................... 17

5. CONCLUSIONS ..................................................... 18

6. REFERENCES ..................................................... 20
1

1. INTRODUCTION

Studies to identify and characterize sensitive subpopulations are an important component

of the U.S. Environmental Protection Agency’s (EPA) drinking water research and assessment

program. These studies provide scientific information to support current Safe Drinking Water

Act (SDWA) rule making activities (e.g., the Stage 2 Disinfectants/Disinfection By-Product Rule)

as well as future regulatory decisions on microbiological and chemical contaminants in drinking

water. Sensitive subpopulation research that is conducted in support of other regulatory statutes

is also relevant to drinking water issues. For example, both the Food Quality Protection Act of

1996 (FQPA) and 1996 Amendments to SDWA require the development of a screening and

testing program to determine whether substances may have adverse effects on the endocrine (i.e.,

hormonal) system in the body. Collectively, these efforts provide critical information to ensure

that public health standards for drinking water (e.g., Maximum Contaminant Levels, or MCLs)

protect both the general population and subpopulations of special concern.

Section 1458(a) of the 1996 Amendments to SDWA requires the Administrator to

conduct “...a continuing program of studies to identify groups within the general population that

may be at greater risk than the general population of adverse health effects from exposure to

contaminants in drinking water. The studies shall examine whether and to what degree infants,

children, pregnant women, the elderly, individuals with a history of serious illness, or other

subpopulations that can be identified and characterized are likely to experience elevated health

risks, including risks of cancer, from contaminants in drinking water. Not later than 4 years after

August 6, 1996, and periodically thereafter as new and significant information becomes available,

the Administrator shall report to the Congress on the results of the studies.”

This report summarizes the status, results and future direction of the Agency’s studies to

identify and characterize sensitive subpopulations that may be at a greater health risk from

exposure to drinking water contaminants than the general public. The focus of this report is on

studies conducted or supported by EPA’s Office of Research and Development and the Office of

Water. Relevant sensitive subpopulation studies from other programs within the Agency are also

summarized. To fully identify and characterize subpopulations that may be more sensitive than

the general population to contaminants in drinking water, the results of EPA studies need to be

considered in the context of the larger body of scientific literature on this topic. 

Section 2 provides a definition of sensitive subpopulations and an overview of waterborne

pathogens and chemicals of special concern. Section 3 describes the risk assessment framework

and research approach used by EPA to address sensitive subpopulation issues. The status and

results of EPA studies in the areas of health effects, risk assessment and exposure are described in

Section 4. Section 5 includes a summary of the report and a discussion of future research

directions. References are found in Section 6.
2

2. BACKGROUND

2.1 Definition of Sensitive Subpopulations

Sensitive subpopulations are defined in this report as groups of individuals who respond

biologically at lower levels of exposure to a contaminant in drinking water or who have more

serious health consequences than the general population. This definition also includes those

individuals who have a greater level of exposure than the general population as a consequence of

biological factors that are characteristic of the group to which they belong. As there is no

universally accepted definition of the term “sensitive subpopulation,” the definition used above is

intended only for the purposes of this report.

Sensitive subpopulations may be considered in the context of various intrinsic (e.g., age,

gender, genetic traits) or acquired (e.g., pre-existing disease, exposure) characteristics that may

modify the risk of illness or disease. Some characteristics of subpopulations may directly

influence the underlying processes involved in the response of an individual to a contaminant, such

as when a pre-existing medical condition may make an individual less resistant to infection. Other

factors, such as socioeconomic status or lifestyle, may have indirect effects. People with low

incomes, for example, may not have the same access to health care as those in higher

socioeconomic groups. The studies described in this report focus primarily on intrinsic and

acquired factors that may directly influence sensitivity.

In some instances, sensitivity factors may be closely linked to each other. For example,

the incidence of certain types of chronic disease appears to be related to age or gender. 

Additionally, people may cycle in and out of being more sensitive than the general population,

depending upon their age or health status at a particular point in time. While intrinsic and

acquired factors are therefore not entirely independent or fixed for the lifetime of an individual,

they provide a useful basis for classifying and studying sensitive subpopulations. 

Data on the number and percentage of individuals in some of the major subgroups in the

U.S. are shown in Table 1. The data indicate that a significant portion of the population belongs

to groups with characteristics that could make them more sensitive than the general population to

the effects of environmental contaminants. 

Among the many factors that may either directly or indirectly influence sensitivity, those

discussed below are considered by EPA to be of greatest relevance for studying sensitive

subpopulations exposed to drinking water contaminants.
3

2.1.1 Intrinsic Factors

Life stage. This category includes groups that may be at increased risk because of

inherent physiological factors or exposure characteristics that are unique to the particular period

of development or age of the individual. These groups include:

• Fetuses, who may be at increased risk if exposure of the pregnant woman to a

toxic agent occurs during critical developmental stages;

• Infants and children, whose defense mechanisms against microbial and chemical

contaminants may not be fully developed;

• The elderly, who may be less able to mount an effective defense against microbial

or chemical contaminants because of a weakened immune system or pre-existing

disease.

Gender. Adult females or males may be more sensitive to the effects of certain

contaminants because of gender-specific physiological factors or differences in the prevalence of

certain types of diseases. For example, men appear to have a greater likelihood of liver

impairments, whereas women are more prone to kidney and thyroid disorders. Pregnancy causes

Table 1. Selected Subpopulations1 in the United States

Subpopulation

Number of

Individuals

Estimated % of

Population

Life Stage

 Pregnant women26,240,000 2.4

 Infants and children (<10 years)338,704,000 14.1

 Elderly (65+ years)334,817,000 12.6

Health Status

 Diabetes (diagnosed and estimated undiagnosed cases)415,700,000 5.8

 Liver impairments5595,000 0.2

 Cardiovascular disease659,700,000 21.7

 AIDS7400,500 0.2

1

 Categories of subpopulations are not mutually exclusive.

2 Ventura et al., 1999.

3

 U.S. Census Bureau, 2000. 

4

 CDC, 1998.

5

 EPA, 1998a.

6

 National Heart, Lung, and Blood Institute, 2000.

7

 CDC, 1999.
4

changes in the endocrine system and metabolism, which may in turn influence the body’s response

to a toxic substance.

Genetic traits. The human body’s ability to detoxify and eliminate a chemical agent or

mount an effective defense against a microbial pathogen is related, in part, to the genetic make up

of the individual. Groups of individuals who share certain genetic characteristics, such as the

altered ability of a gene to produce a critical enzyme involved in the metabolism and detoxification

of chemical toxicant, may therefore be at greater risk than the general population. As a practical

matter, however, genetic influences are complex and still poorly understood. It is unclear to what

extent individuals with heightened sensitivities due to genetic factors meet the statutory criterion

of “subpopulations that can be identified and characterized.”

2.1.2 Acquired Factors

Health status. Groups of individuals with certain pre-existing diseases or clinical

conditions may be more sensitive to the effects of chemicals or microbes present in drinking

water. For example, people with impairments of the liver, kidney or immune system may be less

able to prevent or eliminate the effects of a contaminant due to weakened natural defenses or

detoxification mechanisms. Immunocompromised individuals, including organ transplant patients,

cancer patients being treated with immunosuppressive drugs, and those whose immune system is

weakened by the virus that causes acquired immunodeficiency syndrome (AIDS), are also at

increased risk following exposure to certain infectious and chemical agents.

Exposure. Some groups of individuals share certain biological characteristics that result

in a greater level of exposure than that experienced by the general populations. For example,

although infants consume less water than adults, they may have a higher likelihood of being

exposed to toxic levels of a chemical contaminant because their water ingestion rate is three to

four times greater when calculated on the basis of volume consumed per kilogram of body weight

(EPA, 2000).

2.2 Contaminants of Concern

2.2.1 Waterborne Pathogens

The disinfection of public water supplies has been one of the most successful public health

interventions of the 20th century, dramatically reducing the incidence of waterborne disease

outbreaks throughout the world. Despite the historic success of modern drinking water treatment

techniques, the continued occurrence of waterborne disease outbreaks demonstrates that

contamination of drinking water with pathogenic bacteria, viruses, and parasites still poses a

potentially serious health risk when treatment is inadequate or when there is contamination in the

distribution system. The level of exposure, as well as the characteristics of both the microbe and

the host, influence the outcome of infection. The most common health effect that occurs when a

susceptible individual is exposed to an infectious dose of a waterborne pathogen from drinking

water is an acute form of gastrointestinal disease. Infections are typically mild and transient, but
5

they may also result in more serious illness or even death in the most extreme cases. Some

pathogens may cause longer-term effects, such as heart disease or liver failure.

The pathogenic bacteria most commonly associated with foodborne outbreaks and

waterborne outbreaks from public and private water systems are Escherichia coli, Salmonella,

Campylobacter and Shigella (Gerba et al., 1996). Recently, E. coli O157:H7 was implicated as

the cause of outbreaks in the U.S. and Canada in which several people died. The most commonly

reported cause of waterborne viral gastroenteritis is Norwalk virus. This virus or other members

of the calicivirus family are believed to account for a significant portion of the outbreaks for

which a causative agent has not been determined. Hepatitis A virus and rotavirus have also been

found to cause waterborne disease outbreaks, whereas the extent to which viruses such as

coxsackievirus and echovirus may pose a

risk following contamination of drinking

water is unclear. The protozoan parasites

Giardia lamblia and Cryptosporidium

parvum are among the most threatening

microbiological contaminants found in

drinking water. Giardia has been

responsible for about half of the outbreaks

of disease where the causative agent was

identified. Cryptosporidium has been

responsible for at least 14 outbreaks in the

U.S. since 1985, including a 1993 outbreak

in Milwaukee which caused an estimated

400,000 illnesses and over 50 deaths. A

large number of these deaths occurred in

individuals with weakened immune systems.

“Opportunistic” pathogens are

microorganisms that normally do not pose a

serious risk to healthy individuals but are

more likely to cause disease (often severe) in

individuals with weakened immune systems. 

Cryptosporidium and microsporidia are

opportunistic protozoans that can cause life

threatening illnesses in immunocompromised individuals. Opportunistic bacterial pathogens of

concern include Mycobacterium avium, Legionella species and Pseudomonas aeruginosa. These

microorganisms are able to grow and persist as biofilms on pipes in the distribution system.

Drinking Water Contaminants and

Health Effects of Concern

Pathogens

• Bacteria (e.g., Mycobacterium avium complex, E.

coli O157:H7)

• Viruses (e.g., Norwalk virus)

• Parasites (e.g., Cryptosporidium, Giardia lamblia)

Chemicals

• Disinfection by-products (e.g., trihalomethanes)

• Arsenic

• Sulfate

• Pesticides

• Other inorganic and organic contaminants

Health Effects

• Gastrointestinal illness

• Cancer

• Adverse reproductive outcomes

• Immune system effects

• Neurotoxicity
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2.2.2 Chemicals

A wide variety of naturally occurring and man-made chemicals may contaminate drinking

water. These substances vary considerably in terms of the types and severity of effects that they

elicit in both the general population and in groups that may be more sensitive. The extent to

which a substance may be harmful is a function of exposure, the chemical and physical properties

of the agent, and the inherent sensitivity of the host. At sufficiently high levels of exposure,

chemicals may affect different organ systems and may cause a range of effects (e.g., irritation,

liver disease, adverse reproductive outcomes, cancer). For some chemicals, the parent compound

is responsible for the toxic effect, and the biochemical process called biotransformation (involving

metabolism) is required to detoxify the substance. In other cases, the biotransformation process

itself is responsible for the production of the toxic form of the contaminant.

A considerable amount of information exists on the special sensitivities of certain

subgroups, particularly infants and children, to the drinking water contaminants lead, nitrate/nitrite

and fluoride. Prenatal and postnatal exposures to lead have been shown to increase the risk of

neurodevelopmental damage in infants and children. Nitrate and nitrite are known to pose a risk

to infants whose immature enzyme systems cannot adequately protect hemoglobin, the oxygen

carrying pigment in the red blood cells, from oxidation. The oxidized form of hemoglobin, called

methemoglobin, does not carry oxygen effectively and can be life threatening without immediate

medical attention. Fluoride can cause discoloration of the tooth enamel in children if exposure

occurs during the period of tooth formation. EPA has developed National Primary Drinking

Water Standards (MCLs) for lead and nitrate/nitrite that protect infants and children from harmful

levels of these contaminants in drinking water. A secondary standard has been established for

fluoride to protect children from discoloration of tooth enamel.

In the 1970s, scientists determined that a number of biologically active chemical

substances, referred to as disinfection by-products (DBPs), are formed when chlorine and other

chemical oxidants used to treat drinking water react with naturally occurring materials in the

water. It is now known that disinfected water may contain hundreds of different DBPs, including

trihalomethanes, haloacetic acids, haloacetonitriles, and a number of other types of chlorinated

and/or brominated compounds. Some DBPs have been found to cause adverse health effects in

laboratory animals exposed to high concentrations of these compounds. Epidemiology and

toxicology studies have raised concerns over potential risks of cancer and, more recently, adverse

reproductive effects.

Arsenic has been found to cause different types of cancer and noncancer effects in

populations from various locations throughout the world. As noted by the National Research

Council in their recent report on arsenic in drinking water (NRC, 1999), a variation in

susceptibility to arsenic-induced effects may exist between population groups and individuals. 

The extent to which genetic background, gender and diet may influence sensitivity to this source

water contaminant is unclear. Laboratory animal research on certain pesticides (e.g., chlorpyrifos)

has suggested that the fetus and young animals may not have the same capacity as adults to

detoxify and eliminate these substances from the body. Chemicals known as endocrine disruptors
1

The EPA was required by SDWA to establish a list of contaminants, called the Contaminant Candidate

List (CCL), to aid in priority setting for the Agency’s drinking water program. The CCL contains 60

microbiological and chemical contaminants that are currently not subject to any proposed or promulgated national

primary drinking water regulation, are known or anticipated to occur in public water systems, and may require

regulation under SDWA.

7

affect the natural hormones in the body that are responsible for the maintenance of normal body

function and the regulation of developmental processes. Small disturbances in endocrine function,

especially during certain stages of the life cycle (e.g., development, pregnancy and lactation) can

lead to profound and lasting changes.

3. OVERVIEW OF RESEARCH PROGRAM

3.1 Risk Assessment Framework

The process of risk assessment, as described by the National Academy of Sciences (NAS)

in 1983, provides the framework used by EPA to identify key issues, information gaps and

research needs for sensitive subpopulations (NRC, 1983). The NAS risk assessment paradigm,

which was developed primarily for the assessment of chemical risks, has four main steps: hazard

identification, dose-response assessment, exposure assessment and risk characterization. 

Although there are some features of microbiological risk assessment that make it distinct from the

assessment of chemical risks (e.g., pathogen viability, infectivity and secondary spread), the NAS

framework may be used as a guide for both types of contaminants. This Report to Congress

focuses primarily on the first three steps of the risk assessment process. Health effects studies

cover the first two steps (hazard identification and dose-response assessments), whereas exposure

studies cover the third step. The Agency will conduct formal risk characterizations (step four) as

part of the regulatory development process for specific contaminants of concern. 

3.2 Identification and Prioritization of Research Needs

Studies conducted by EPA to address sensitive subpopulation issues have been guided by

the Agency’s research plans and strategies (EPA, 1997; 1998b; 1998c; 1999b), expert workshops

on special topics (e.g., EPA, 1993; 1998d), and consultations with other Federal agencies and

research organizations. In addition, a special series of meetings on sensitive subpopulations was

held with drinking water stakeholders as part of the SDWA 25th Anniversary Futures Forum

activities. Participants in these meetings emphasized the need for better information to

characterize sensitive subpopulations, the contaminants that pose special risks, and the exposure

levels at which the effects may occur.

EPA has placed considerable emphasis on research to address sensitive subpopulation

issues for waterborne pathogens and chemicals on the current drinking water regulatory agenda

(e.g., Cryptosporidium, DBPs). Studies are increasingly focusing on pathogens and chemicals

that may be candidates for future regulations, including those on the EPA’s Contaminant

Candidate List1 (EPA, 1998e). 

3.3 Research Approach
2

The Microbial/Disinfection By-Product Research Council was established in 1995 by the EPA and

AWWARF for the purpose of making funding decisions on cooperative research. The Council is composed of

three EPA representatives, three members of the AWWARF Board of Trustees, and three representatives of the

Disinfectant/Disinfection By-Product Rule Regulatory Negotiation group. 

8

Studies of sensitive subpopulations typically involve multidisciplinary research and

assessments to identify a range of possible health outcomes, including cancer, reproductive

toxicity, gastrointestinal illness, and other adverse health effects. EPA is using several approaches

to address sensitive subpopulation issues: 1) population-based epidemiology studies to identify

potentially harmful contaminants, risk factors and sensitive subpopulations; 2) clinical studies to

evaluate the effects of specific contaminants and the host factors that influence the disease

process; 3) studies in laboratory animals to provide hazard identification and dose-response data,

as well as to elucidate how contaminants cause their effects; 4) the development and validation of

standardized test methods for the evaluation of contaminants that may be of special concern to

certain subpopulations; and 5) the development of improved methods and data bases to better

estimate total exposures to drinking water contaminants from all relevant sources and routes (i.e.,

oral, dermal and inhalation). EPA is also compiling existing data to assist in characterizing

specific sensitive subpopulations, and is developing improved risk assessment methods that will

permit better use of all available information on health effects and exposure.

To address the broad scope of sensitive subpopulation research issues, EPA has

established partnerships to leverage resources and capabilities with various Federal and state

agencies, universities, the water industry and other public or private research entities. 

Collaborations have been established with the Department of Health and Human Services’ Centers

for Disease Control and Prevention (CDC) and National Institute of Environmental Health

Sciences (NIEHS) to address several high priority epidemiology and toxicology research needs. 

For example, EPA, CDC and NIEHS established eight Centers of Excellence in Children’s

Environmental Health and Disease Prevention Research. The Centers are conducting basic and

applied research in combination with community-based prevention efforts. EPA and the

American Water Works Association Research Foundation (AWWARF) are co-funding several

important drinking water research studies under the auspices of the Microbial/Disinfection ByProducts Research Council2

. The Agency’s extramural grants program supports research on

waterborne pathogens, chemicals in drinking water and endocrine disruptors in universities and

non-profit research organizations throughout the country. In addition, EPA has worked on

endocrine disruptor testing and research issues in close collaboration with international

organizations and advisory groups, particularly the Organization of Economic Cooperation

(OECD) and Development and the Endocrine Disruptor Screening and Technical Advisory

Committee (EDSTAC).
9

4. EPA STUDIES ON SENSITIVE SUBPOPULATIONS 

Studies conducted or supported by EPA to

identify and characterize sensitive subpopulations can be

described in the context of the various intrinsic and

acquired factors described in Sections 2.1.1 and 2.1.2. 

While many of the studies are still in progress, those that

have been completed are providing important insights to

improve risk assessments and guide future research

activities. A description of EPA research and assessments

on sensitive subpopulations is found below.

4.1 Life Stages

4.1.1 Fetuses

Disinfection by-products. One of the most

important investigations to draw attention to the issue of DBPs and adverse reproductive

outcomes was a prospective epidemiology study, funded in part by EPA, of 5,144 pregnant

women in California (Waller et al., 1998). The authors of this study reported an association

between exposure to high levels of trihalomethanes and the incidence of miscarriage. The

potential for DBPs to cause adverse reproductive outcomes was also examined in an EPA-funded

study in Colorado, in which the authors reported an association between high trihalomethane

levels and low birth weight (Gallagher et al., 1998). These studies and a small number of other

published reports have provided some clues suggesting that fetuses could be sensitive to DBPinduced toxic effects. However, the uncertainties in the epidemiologic data, particularly with

respect to the exposure assessment, preclude a more definitive conclusion about the possible

association between DBPs and adverse reproductive outcomes. 

EPA is supporting several studies to address the need for additional information on this

issue, including: 1) a reanalysis of the California spontaneous abortion study using improved

exposure data; 2) an ongoing prospective pregnancy study in California to which information on

DBP levels from selected drinking water utilities is being added; 3) a major new spontaneous

abortion study in North Carolina, Virginia and Texas, co-funded with AWWARF; and 4) birth

defects studies that are being conducted in conjunction with CDC’s Centers for Birth Defects

Research and Prevention in locations throughout the country. Efforts to improve the exposure

assessment component of epidemiology studies are discussed in Section 4.5 of this Report.

To further explore the relationship between DBP exposures and adverse reproductive

outcomes, EPA has developed an extensive extramural and in-house toxicology research

program. A key feature of the extramural effort is a collaborative research project with the

National Toxicology Program (NTP) of the National Institute of Environmental Health Sciences. 

NTP conducts screening studies in rodents using a standardized protocol to evaluate the effects of

Factors Considered in Studies of

Sensitive Subpopulations

Life stage

Fetuses

Infants and children

Elderly

Gender

Genetic traits

Health status

Pre-existing diseases

Immune system deficiencies

Exposure 
10

DBPs on both male and female reproductive systems, as well as on fetal development. Studies

have been conducted on a number of individual DBPs, and an evaluation of a mixture of four

haloacetic acids is now underway. Sodium bromate and bromochloroacetic acid have been shown

to exhibit selective reproductive toxicity at high experimental exposure doses (NTP, 1996; 1998). 

Additional studies are being conducted to follow up on these results in more detail.

EPA scientists are currently conducting animal studies on the potential for two DBPs,

dibromoacetic acid and bromochloroacetic acid, to delay puberty and alter male reproductive

competence in the offspring. Other ongoing studies are evaluating the effects of exposure to

mixtures of DBPs on reproductive outcomes. A multigeneration study has been initiated to

evaluate the potential effects of a priority DBP (bromochloroacetic acid) following long-term, low

dose exposure throughout the life cycle of the experimental animal. 

In 1998, EPA published a report that evaluated the available data for each of the

disinfectants and DBPs, for which Maximum Residual Disinfectant Level Goals (MRDLGs) and

Maximum Contaminant Level Goals (MCLGs), respectively, were developed in support of the

final Stage 1 D/DBP Rule (EPA, 1998f). These nonenforceable health goals are set at exposure

levels for which no known or anticipated adverse health effects occur, including an adequate

margin of safety. On the basis of this analysis, EPA concluded that the MRDLGs and MCLGs for

all the D/DBPs in the Stage 1 Rule were protective of fetuses, infants and children.

Arsenic. EPA scientists and collaborators are studying sensitive subpopulation issues for

arsenic in regions of the world where the drinking water is highly contaminated. A study in Chile

evaluated the potential association between exposure to arsenic in drinking water and the risk of

mortality to the fetus and newborn infants (Hopenhayn-Rich et al., 2000). While the results were

suggestive of a possible association at high exposure levels, the data are still insufficient to allow

firm conclusions. A second Chilean study is examining the possible association of low level

exposure to arsenic with low birth weight, prematurity, and indicators of maternal health. A study

to evaluate the health effects of arsenic has also been initiated by EPA researchers and

collaborators in Inner Mongolia. A variety of health endpoints, including adverse reproductive

outcomes, will be examined in an area with a wide range of arsenic concentrations in the drinking

water supply.

Pesticides/endocrine disruptors. Under the EPA’s research programs on pesticides and

endocrine disruptors, a wide range of studies are being conducted to provide insights into risks

that these chemicals pose to the developing fetus and to other life stages. EPA researchers have

demonstrated that selected organophosphate, triazine and dithiocarbamate pesticides can cause

adverse effects on the development of animals when exposure to high experimental doses occurs

during critical periods of development (Cooper et al., 1999). Current research on the mode of

action of some of these agents is being conducted to help evaluate the extent to which these

effects may be relevant to humans at the lower exposure concentrations that may occur in

drinking water.
11

In support of both Food Quality Protection Act (FQPA) and SDWA, significant progress

has been made in the development of standardized and validated methods for testing of chemicals

that may have estrogenic or other endocrine effects in humans. Research has focused on the

development of mammalian, non-mammalian and in vitro (i.e., cell culture) screening assays. The

assays will be used to help identify chemicals that will require further testing, to provide

information on the mechanisms by which they may cause their effects, and to help understand the

stages of the life cycle that may be most susceptible to toxic insult with these substances. Some

of these screening assays have reached the pre-validation stage. EPA estimates that all of the

assays under development will be validated by 2003.

4.1.2 Infants and Children

Waterborne pathogens. To evaluate the factors that may result in a greater sensitivity of

infants and children following exposure to waterborne pathogens, EPA is conducting a review of

data on various physiological and exposure-related characteristics of these groups that can

influence infection and disease outcome. The immaturity of the child’s organ systems, particularly

the immune system and gastrointestinal tract, is a factor that can increase the likelihood of

infection and the severity of the illness. Inherent exposure-related physiological factors (e.g., a

higher water ingestion per unit body weight compared to adults) may also contribute to a greater

risk.

The issue of whether children are more likely than adults to experience waterborne

gastrointestinal illness is being examined as part of a series of studies being conducted or

supported by the Agency in different parts of the U.S. Researchers are evaluating the health

status of families in three communities before and after the local water utilities upgrade their

treatment systems. The results of the first of these “community intervention” studies will be

available in FY2001. As part of the EPA/CDC program of waterborne disease occurrence studies

(required by the 1996 SDWA Amendments), researchers from the University of California at

Berkeley are conducting a large epidemiology study in a Midwestern community that may provide

additional information on the extent to which children and other demographic groups are more

sensitive to waterborne infectious disease. Beginning in 1998, EPA supported the addition of a

water component to the CDC’s Foodborne Diseases Active Surveillance Network (FoodNet). 

This multi-state gastrointestinal illness surveillance program is collecting information on the risks

to children and other demographic groups from exposure to microbiological contaminants in food,

drinking water and recreational water.

To determine the influence of age and other demographic parameters on sensitivity to

microbial diseases and mortality, EPA conducted an analysis of data from FoodNet (prior to the

inclusion of the water component) and from waterborne disease outbreaks that were reported

through 1994 (EPA, 1998g). Information from FoodNet indicated that there have been many

more cases of foodborne illnesses in infants and children than in other age groups. The

waterborne disease outbreak data generally did not reflect a greater sensitivity of infants and

children. These results should be interpreted with caution due to the incomplete nature of the
12

information examined and the possible influence of biases in reporting data for certain age groups

(e.g., there may be a greater frequency of reporting cases in the very young and elderly by adult

caregivers). 

Chemicals. Several assessment-related activities are being conducted by the Agency to

better characterize the risks to children following exposure to chemicals in drinking water. EPA

will soon publish the results of a workshop in which experts reviewed information on critical

“windows” of exposure during which time the developing organism (fetus, newborn, child and

adolescent) may be particularly sensitive to the effects of selected chemicals. Other EPA projects

that are underway include an assessment of the potential risk of childhood cancers associated with

exposure to chemicals in drinking water, and an analysis of the potential relationship between

early-life exposures and lifetime cancer risks. In addition to these efforts, EPA is evaluating

innovative statistical approaches (i.e., Benchmark Dose and Categorical Regression) to determine

their applicability in assessments of the dose-response in children for two drinking water

contaminants, chloral hydrate and nitrate/nitrite. 

In response to concerns about the potential sensitivity of infants to sulfate-induced

diarrhea, the EPA supported a study using neonatal piglets as a model to evaluate the effects of

inorganic sulfate in drinking water on bowel function in human infants (Gomez et al., 1995). The

results of this study did not indicate that infants may be particularly sensitive to sulfate, as the

presence of sulfate in drinking water at levels of up to 1200 mg/L (as sodium sulfate) produced

minimal or no adverse health effects. A similar absence of effects was observed in EPAsponsored studies with adult volunteers who had no previous exposure to sulfates in drinking

water (Heizer et al., 1997). The results suggest that transient populations may not have a greater

sensitivity to sulfate as had been previously suggested (EPA, 1999a).

EPA is supporting an epidemiology study of childhood sensitivity to pesticides in which

several routes of exposure (i.e., ingestion, dermal and inhalation) to persistent organic compounds

are being evaluated. In another study conducted as part of the National Health and Nutrition

Examination Survey (NHANES), EPA is supporting data collection and analysis of serum or urine

levels of several organochlorine, organophosphate and pyrethroid pesticides, as well as selected

polychlorinated biphenyls (PCBs). Samples are being taken from approximately 1,000 children

and young adults between 6 to 19 years of age, of which a subset will be assessed for deficits in

thyroid function. 

Finally, the Border XXI Program is a cooperative binational effort between several

Federal agencies of the U.S. and Mexico to help ensure human and environmental health along the

U.S.-Mexico border. As part of this program, EPA is conducting multimedia studies to

characterize exposures of children to various pesticides and metals. The data will provide a basis

to validate age-dependent exposure models that incorporate activity patterns, water consumption,

diet and nutritional status.
13

4.1.3 The Elderly

As people age, sensitivity may change due to alterations in the way the body responds to a

contaminant. Altered biochemical processes (e.g., metabolism) that are responsible for the

detoxification or activation of a toxic agent may impact sensitivity to a chemical contaminant. A

less active immune system or an increased likelihood of pre-existing disease may be risk factors

for disease caused by waterborne pathogens. To obtain information on pre-existing diseases that

are most common in the elderly, EPA collected data from several national surveys on the

prevalence of chronic disease in the U.S. The surveys indicated that osteoporosis, cardiovascular

disease, diabetes and hypertension are more prevalent in individuals over 65 years of age than in

the remainder of the population (EPA, 1998a). 

EPA’s waterborne disease occurrence studies are examining the extent to which the

elderly and other subgroups may be more susceptible than the general population following

exposure to waterborne pathogens. With regard to chemical exposures, EPA researchers are

developing a special animal model that can be used in studies to evaluate if older rodents may be

at greater risk than other age groups from exposure to chemical contaminants. Results obtained

to date indicate that the model may be a good tool for studying age-related toxic effects on the

liver. 

4.2 Gender

Adult males and females show distinct differences in the incidence of certain chronic

disorders, the presence of which may reduce the ability of the affected individual to mount an

effective defense against subsequent exposure to a waterborne pathogen or toxic chemical. 

Females appear to be more prone to anemia, osteoporosis, kidney problems and thyroid disorders,

while males have a higher reported incidence of liver disease (EPA, 1998a).

EPA research has shown that exposure of adult female rodents to certain pesticides (e.g.,

atrazine) can cause changes in the regulation of reproductive function (Cooper et al., 2000). To

determine if similar results can be observed for DBPs, Agency researchers are examining if DBP

exposures can impact hormonal cycles in nonpregnant female rodents. An EPA-funded study at

Colorado State University is following up on findings by EPA scientists that sperm production in

rodents exposed to high concentrations of selected DBPs may be adversely affected. These new

studies are being conducted in rabbits, which have a longer period of reproductive development

than that of rodents.

EPA studies with the haloacetic acid family of DBPs have demonstrated that certain

brominated by-products can cause decreases in the sperm quality of male rodents following

exposure to high experimental doses (Linder et al., 1995). Studies are now underway to

determine if these effects can be observed at lower exposure levels. In the course of these

investigations, EPA researchers made an important scientific finding that could lead to the

development of a sensitive biological marker, or biomarker, of male fertility (Klinefelter et al.,
14

1997). The specific protein on the sperm membrane (SP22) that is correlated with sperm fertility

may serve as an invaluable tool for determining if low level exposures to DBPs are associated

with adverse male reproductive effects. Furthermore, this biomarker could have public health

implications that extend well beyond the original drinking water context for the research. 

4.3 Genetic Traits

With the tremendous growth over the past decade in research related to the Human

Genome Project, interest and knowledge regarding the genetic underpinnings of disease and

susceptibility have greatly increased. As described below, EPA scientists have begun evaluating

and applying new tools to study sensitive subpopulation issues for both waterborne pathogens and

chemical contaminants in drinking water. The genetic influences on sensitivity to environmental

contaminants are complex and only beginning to be understood. As a practical matter, it is

therefore not clear to what extent such factors can be used to define groups that meet the

statutory criterion of “subpopulations that can be identified and characterized.”

Waterborne pathogens. Sensitivity to infection and disease caused by pathogenic

bacteria, viruses or parasites is based in part on host susceptibility or resistance factors that may

be under genetic control. Changes in sensitivity may be due to alterations in genes that are

involved in the body’s immune defense system or that code for certain receptors on the surface of

host cells that are attacked by the infectious agent. Genetically induced changes in patients with

an unrelated disease may predispose these patients to infections by waterborne pathogens. 

The presence of these genes provides an opportunity to identify biomarkers of

susceptibility. As described in a report that will soon be finalized by EPA, a review of the

literature was conducted to identify potential biomarkers of susceptibility in animals and/or

humans for ten waterborne pathogens: Mycobacterium species, Helicobacter pylori,

Pseudomonas species, Legionella species, coxsackievirus, adenovirus, hepatitis A, Entamoeba

histolytica, Cryptosporidium, and Toxoplasma gondii. Due to the highly complex nature of this

issue, additional studies are necessary to determine the extent to which these biomarkers are

useful in identifying subpopulations that may be more sensitive to infection with waterborne

pathogens.

Chemicals. Metabolism, which is mediated by enzymes that are under genetic control, is

known to play an important role in the toxicity of chemicals. Individuals with either a lower

capacity to detoxify chemicals or a greater capacity to activate chemicals, due to variability in the

quantity or activity of metabolic enzymes, may be at greater risk of cancer or other adverse health

effects. EPA is conducting an analysis of genetic and other factors that may play a role in the

metabolic detoxification or activation of chemical contaminants. This project involves an

evaluation of data on the impact of age, gender, ethnicity, diet, common pharmaceuticals and

behavioral characteristics (smoking, alcohol ingestion) for two important enzyme systems, the

cytochrome P-450 isoforms and the glutathione-S-transferases. Related to this effort is a research

project to determine the extent of human interindividual variability (adults and children) in the
15

expression of cytochrome P-450 isoforms in samples of human liver cells derived from organ

donors. The ultimate goal is to develop a tool for identifying subpopulations that may be more

sensitive because of inherent differences in the ability to metabolize chemical toxicants. 

EPA investigators are conducting animal studies on one aspect of how genetic make-up

may predispose some individuals to DBP-induced cancer. Specifically, efforts are being directed

toward determining whether individuals whose blood cells express different forms or amounts of

glutathione-S-transferases vary in sensitivity to the genotoxic effects of selected DBPs. This type

of study could have broad applicability, since the glutathione-S-transferase family of enzymes

comprises a fundamental detoxification mechanism for several classes of toxic substances.

EPA researchers are also using a rat model of hereditary kidney cancer to evaluate the

influence of genetic predisposition on the risk posed by exposure to DBPs. The objectives are to

determine whether this genetically-altered strain of rat is more sensitive to the effects of exposure

to trihalomethanes, and if the resulting tumors share critical features of cancers that may be linked

with human exposure to DBPs.

This line of investigation is being extended to other chemical contaminants. The

metabolism of arsenic by enzymes under genetic control is believed to be an important

determinant of its toxicity and carcinogenicity. Some data from the published literature suggest

that the pattern and extent of arsenic metabolism may differ among individuals. Results of a study

conducted by EPA researchers in an arsenic-exposed population in Utah showed no differences in

the amounts of the various forms of arsenic found in the urine of adults and children (Calderon et

al., 1999), suggesting that arsenic may be metabolized in a similar manner in both of these

subgroups. The data are being further analyzed to develop gender-related metabolic profiles. 

Related research in rodents includes efforts to develop an animal model for investigating

genetically determined variations in the metabolism of arsenic, and studies to evaluate the

influence of dietary constituents (e.g., folate and selenium) on this process.

Along with the increased interest in the genetic foundation of disease has come

tremendous innovation in the tools for investigating gene expression. Two complementary

techniques that are rapidly becoming essential for such research are DNA microarrays and genetic

engineering. Microarrays are glass slides or nylon filters onto which are spotted thousands of

genes (DNA). When complementary DNA obtained from a tissue sample is overlaid onto the

spotted template, it binds to the arrayed genes and can be detected through the use of fluorescent

probes or a radioactive label. In such a manner, investigators are able to rapidly screen how

toxicants can influence the expression of thousands of genes at a time. Over the past year, EPA

investigators have been collaborating with Federal, academic, and industry researchers to develop

methods for applying this powerful technology to elucidate the genetic mechanisms of action of

environmental toxicants, including DBPs. Once affected genes are identified, investigators can

use genetic engineering techniques to further study how specific genetic abnormalities alter the

risk posed by exposure to drinking water contaminants.
16

4.4 Health Status

As discussed earlier, individuals with a pre-existing medical condition may have reduced

resistance to subsequent infection or toxic insult. Most of the studies conducted by EPA relating

to health status have focused on individuals with weakened immune systems. The immune system

is complex, involving a variety of different types of cells and processes that comprise an

individual’s defense system against infection or disease. Because of this complexity, many

different approaches are used to test immune status following exposure to a toxic or pathogenic

agent. To assist risk assessors in evaluating the results of these tests, EPA compiled information

on the various assays and prepared a compendium that describes their strengths and weaknesses

(EPA, 1998h).

EPA is conducting several different types of studies in the laboratory, clinic and field to

evaluate the impact of host immune status on sensitivity. For individuals with weakened immune

systems, particularly those with acquired immunodeficiency syndrome (AIDS) and patients on

immunosuppressive drugs, infections with the pathogen Cryptosporidium can be life-threatening. 

EPA scientists and grantees are conducting research on various animal models to examine the

impact of compromised host immune condition on infection with this parasite. Pilot epidemiology

studies are evaluating the role of drinking water as a source of Cryptosporidium infections in a

hospital setting and in a population that is positive for the virus that causes AIDS. EPA

researchers and collaborators have also studied the role of drinking water as a source of another

opportunistic pathogen that poses a special risk to people with weakened body defenses. In a

recently published study (Aronson et al., 1999), investigators found Mycobacterium avium in

potable water from selected homes, large buildings and hospitals. Many of the isolates from the

water and from immunocompromised patients were found to share similar patterns of genetic

material. The methodology used in this study was inadequate for establishing a clear link between

M. avium infections and exposure through the drinking water, but the results do provide a basis

for additional studies being planned by EPA to further evaluate this issue.

EPA has supported several studies to determine the infectious dose and role of protective

immunity in healthy human volunteers exposed to the pathogens Cryptosporidium and Norwalk

virus. This research has suggested that a low number of pathogens is required to establish

infections in healthy adults, and that (at least for Cryptosporidium) the immune system plays an

important role in protecting people who have been exposed previously (Chappell et al., 1999). 

These results further highlight the special risks that some pathogens can pose to individuals whose

defense systems are compromised. 

It has been well established that an individual with a weakened immune system is at

greater risk of infection and serious illness following exposure to a microbial pathogen. If a

chemical in drinking water is immunotoxic, this could render the individual more sensitive to

infection with a waterborne pathogen. In the collaborative EPA/NTP toxicity screening program,

researchers are evaluating the potential of five DBPs (dibromoacetic acid, sodium bromate,

sodium chlorite, dichloroacetic acid and chloroform) and the disinfectant chloramine to cause

immunotoxic effects in experimental animals. Screening studies have been completed on two of
17

the DBPs to date. Dibromoacetic acid was found to alter the immune response in an initial high

dose study, and additional tests are now being conducted to further evaluate if effects can be

observed at lower doses (NTP, 1999). Sodium bromate did not alter the immune responsiveness

of treated animals (NTP, 2000). 

4.5 Exposure 

A critically important area of research to help identify sensitive subpopulations in DBP

epidemiology studies is the development of improved data and methods for estimating exposures. 

Several approaches are being used, including: 1) developing and applying geographic information

systems to better manage exposure and health data; 2) incorporating lifestyle questions (e.g.,

water consumption and use) into survey questionnaires to better gauge exposures to DBPs by the

oral, dermal and inhalation routes; 3) using distribution system modeling techniques to estimate

DBP exposures at or near the homes of study participants; and 4) determining concentrations of

DBPs in blood samples for comparison with levels found in drinking water taken from the

distribution system and home. EPA is also merging activity pattern data with existing multiple

route exposure models to better estimate the variability in total exposure to DBPs for different

population groups.

EPA is coordinating several studies to characterize multiple-source, multiple-route

exposures to environmental contaminants across seven states. This effort involves a consortium

of research organizations in the National Human Exposure Assessment Survey (NHEXAS). Two

of the studies include representative samples of the general population, and a third study will

compare urban and rural populations. Classes of contaminants being evaluated include pesticides,

volatile organic compounds, and metals.

In conducting risk assessments on special populations of interest, it is important to

consider information on levels of drinking water intake that may be specific to that particular

group of individuals. Several approaches are being used to develop these intake data. EPA has

conducted an extensive review of data on drinking water intake rates from the U.S. Department

of Agriculture’s Continuing Survey of Food Intake by Individuals (EPA, 2000). Intake of tap

water, bottled water and water from other sources was evaluated. Water consumed directly as

well as water used in the preparation of juices, coffee, reconstituted soup mixes and other similar

foods were considered. The data were found to generally support the Agency’s use of 2 L/day

for adults and 1 L/day for children as upper-percentile tapwater intake rates. Pregnant women do

not differ significantly in their water ingestion compared to women of child-bearing age. 

However, lactating women ingest significantly more water than pregnant or control (nonpregnant, non-lactating) women. When considering water ingestion in units of milliliters of water

ingested per kilogram of body weight per day, babies younger than one year old have an ingestion

rate that is approximately three to four times higher than that of the general population. It is

reasonable to assume individuals who engage in vigorous work or exercise, particularly in warmer

climates, have a higher daily intake of water than the general population. An analysis of

consumption according to the source of the water indicates that community water supplies
18

account for 75% of the water consumed, followed by bottled water (13%) and spring, well and

cistern water combined (10%). 

Data on drinking water consumption patterns for various age groups and on the

contribution of contaminants from drinking water exposures are also being evaluated from the

NHEXAS project and other data sources. The results will be compiled into an updated childhood

exposure factors data base. In addition, methods are being developed to better scale physiological

parameters for children versus adults, which will lead to improved quantitative estimates of risk

for children. 

To assess total dietary exposure to contaminants, EPA has developed a PC-based Dietary

Exposure Potential Model (DEPM). The model can help identify food and drinks that are

relatively high contributors to contaminant exposure by consumption, and it can provide a relative

exposure estimate for the consumption of tapwater only or tapwater used in food/drink

preparation and food. The DEPM can also provide an estimate of exposure for populations based

on age, ethnic origin, and region for contaminants included in various residue surveys. Currently,

EPA is using the model in its risk assessment of arsenic to identify foods high in total arsenic

content.

5. CONCLUSIONS

EPA is conducting and supporting a wide range of studies to identify and characterize

groups that may be at greater health risk than the general population following exposure to

contaminants in drinking water. Important factors that are being investigated include life stage

(i.e., fetuses, infants and children, the elderly), gender, genetic traits, health status and exposure. 

Research to date has emphasized waterborne pathogens and chemicals from a public health and

regulatory perspective, with efforts now expanding to address “emerging” contaminants that may

be considered in future regulatory decision making. Because of the importance and broad scope

of this issue, EPA has established collaborations and has leveraged funding for research with

various Federal agencies, the water industry and other research entities. 

The EPA studies that have been completed to date are providing important data to

improve risk assessments and guide future research activities on sensitive subpopulations. New

insights are expected within the next few years as the results of ongoing studies become available. 

To fully identify and characterize groups that may be more sensitive than the general population

to contaminants in drinking water, the results of EPA studies need to be considered in the context

of the larger body of scientific literature on sensitive subpopulations. 

Major highlights of EPA’s sensitive subpopulation studies on waterborne pathogens and

chemicals in drinking water are summarized below:

Waterborne pathogens. The results of an analysis of physiological and exposure-related

characteristics of infants and children suggest that this subpopulation may be more sensitive than
19

the general population to waterborne pathogens. This is consistent with data collected on the

demographics of foodborne illnesses, but the data from waterborne disease outbreaks in the U.S.

are less conclusive. The results of several epidemiology studies and surveys that are currently

underway should provide important information on the risks that pathogens in drinking water

pose to infants, children, and other age groups. Individuals with pre-existing disease, particularly

those with weakened immune systems, are known to be at increased risk following exposure to

opportunistic pathogens such as Cryptosporidium. EPA is conducting research in the laboratory

and field to further evaluate the impact of host immune status on sensitivity to these agents.

Chemicals. Studies conducted by EPA and others have raised concerns about a potential

risk of adverse reproductive outcomes following maternal exposure to DBPs. EPA research has

also shown that exposure of laboratory animals to high levels of certain pesticides can cause

adverse developmental effects. Current laboratory and field research on pesticides will contribute

to a better understanding of the potential risks of these contaminants to subpopulations of special

concern. In studies to evaluate the health effects of sulfate, EPA researchers and collaborators

found that piglets (as a model for human infants) and previously unexposed adults were not

particularly sensitive to the effects of this contaminant in drinking water. 

Considerable progress has been made since the enactment of the 1996 SDWA

Amendments in the development of improved methods for evaluating toxicity, assessing

exposures, and conducting risk assessments of contaminants and subpopulations of special

concern. These new tools will enable Agency scientists to generate critical data and conduct

scientifically sound risk assessments in support of the requirements of SDWA and other

regulatory statutes.

Based on a consideration of potential public health risks and the findings of studies to

date, near-term research priorities include studies of DBP exposures and adverse reproductive

outcomes, risks to infants and children from exposure to waterborne pathogens, and risks to

individuals whose health status is compromised. A greater emphasis will be placed on research to

examine the elderly as a possible sensitive subpopulation. Efforts will be made to take advantage

of new advances in molecular biology to study genetic factors involved in environmentallyinduced disease. The development and application of improved methods for toxicity evaluations,

exposure assessment and risk assessment will also continue to be priorities. The results of these

studies will help to provide a sound scientific basis for regulations and guidance to protect the

public health of the 250 million people, including sensitive subpopulations, who get their water

from public water systems.
20

6. REFERENCES 

Aronson, T., A. Holtzman, N. Glover, M. Boian, S. Froman, O.G.W. Berlin, H. Hill, and G.

Stelma, 1999. Comparison of large restriction fragments of Mycobacterium avium isolates

recovered from AIDS and non-AIDS patients with those of isolates from potable water. J. Clin.

Microbiol., 37(4):1008-1012.

Calderon, R.L., E. Hudgens, X.C. Le, D. Schreinemachers, and D.J. Thomas, 1999. Excretion of

arsenic in urine as a function of exposure to arsenic in drinking water. Environ. Health Perspect.,

107(8):663-667.

CDC, 1998. National diabetes fact sheet: National estimates and general information on

diabetes in the United States, Revised edition. U.S. Department of Health and Human Services,

Centers for Disease Control and Prevention, Atlanta, GA.

CDC, 1999. HIV/AIDS surveillance report. 11:2. U.S. Department of Health and Human

Services, Centers for Disease Control and Prevention, Atlanta, GA.

Chappell, C.L., P.C. Okhuysen, C.R. Sterling, C. Wang, W. Jakubowski, and H.L. Dupont, 1999. 

Infectivity of Cryptosporidium parvum in healthy adults with pre-existing anti-C. parvum serum

immunoglobulin G. Am. J. Trop. Med. Hyg., 60(1): 157-164.

Cooper, R.L., J.M. Goldman, and T.E. Stoker, 1999. Neuroendocrine and reproductive effects of

contemporary-use pesticides. Toxicol Ind. Health, 15(1-2):26-36.

Cooper, R.L., T.E. Stoker, L. Tyrey, J.M. Goldman, and W.K. McElroy, 2000. Atrazine disrupts

the hypothalamic control of pituitary-ovarian function. Toxicol. Sci., 53(2):297-307.

EPA, 1993. Report of the panel on reproductive effects of disinfection by-products in drinking

water. U.S. Environmental Protection Agency/International Life Sciences Institute, September,

1993.

EPA, 1997. Research plan for microbial pathogens and disinfection by-products in drinking

water. EPA 600-R-97-122, December 1997. Office of Research and Development, U.S.

Environmental Protection Agency.

EPA, 1998a. Demographic distribution of sensitive population groups. Office of Science and

Technology/Office of Water, U.S. Environmental Protection Agency. Prepared by SRA

Technologies, Inc. (O’Day, R., J. Rench, R. Oen, and A. Castro), Falls Church, VA.

EPA, 1998b. Research plan for arsenic in drinking water. EPA 600-R-98-042. Office of

Research and Development, U.S. Environmental Protection Agency. 
21

EPA, 1998c. Research plan for endocrine disruptors. EPA 600-R-98-087. Office of Research

and Development, U.S. Environmental Protection Agency.

EPA, 1998d. EPA panel report and recommendations for conducting epidemiological research

on possible reproductive and developmental effects of exposure to disinfected drinking water. 

National Health and Environmental Effects Research Laboratory, U.S. Environmental Protection

Agency, February 12, 1998.

EPA, 1998e. Announcement of the drinking water contaminant candidate list. Federal Register,

63(40):10274-10287.

EPA, 1998f. Health risks to fetuses, infants, and children (final Stage 1 D/DBP Rule). Office of

Science and Technology/Office of Water, U.S. Environmental Protection Agency, October 1998.

EPA, 1998g. Morbidity and mortality demographics for foodborne and waterborne microbial

disease. Office of Science and Technology/Office of Water, U.S. Environmental Protection

Agency. Prepared by SRA Technologies, Inc. (Rench, J., R. O’Day, H. Vandermer, and J.

Almond), Falls Church, VA.

EPA, 1998h. Compendium of available immunotoxicity screening tests. Office of Science and

Technology/Office of Water, U.S. Environmental Protection Agency. Prepared by SRA

Technologies, Inc. (Albright, J.F., and I.C. Felkner), Falls Church, VA.

EPA, 1999a. Health effects from exposure to sulfate in drinking water workshop. EPA 815-R99-002. Office of Water, U.S. Environmental Protection Agency.

EPA, 1999b. Strategy for research on environmental risks to children. EPA/600/R-00/068. 

Office of Research and Development, U.S. Environmental Protection Agency, October 2000.

EPA, 2000. Estimated per capita water ingestion in the United States. EPA-822-00-008. 

Office of Science and Technology/Office of Water, U.S. Environmental Protection Agency.

Gallagher, M.D., J.R. Nuckols, L. Stallones, and D.A. Savitz, 1998. Exposure to trihalomethanes

and adverse pregnancy outcomes. Epidemiology, 9:484-489.

Gerba, C.P., J.B. Rose, and C.N. Haas, 1996. Sensitive populations: who is at the greatest risk? 

Intl. J. Food Microbiol, 30:113-123.

Gomez, G.G., R.S. Sandler, and E. Seal, 1995. High levels of inorganic sulfate cause diarrhea in

neonatal piglets. J. Nutr., 125:2325-2332.

Heizer, W.D., R.S. Sandler, E. Seal, S.C. Murray, M.G. Busby, B.G. Schliebe, and S.N. Pusek,

1997. Intestinal effects of sulfate in drinking water on normal healthy subjects. Dig. Dis. Sci.,

42(5):10555-1061.
22

Hopenhayn-Rich, C., S. Browning, I. Hertz-Picciotto, C. Ferreccio, C. Peralta, and H. Gibb,

2000. Chronic arsenic exposure and risk of infant mortality in two areas of Chile. Environ.

Health Perspect., 108(7):667-673.

Klinefelter, G.R., J.W. Laskey, J. Ferrell, J.D. Suarez, and N.L. Roberts, 1997. Discriminant

analysis indicates a single sperm protein (SP22) is predictive of fertility following exposure to

epididymal toxicants. J. Androl., 18(2):139-150.

Linder, R.E., G.R. Klinefelter, L.F. Strader, M.G. Narotsky, J.D. Suarez, N.L. Roberts, and S.D.

Perreault, 1995. Dibromoacetic acid affects reproductive competence and sperm quality in the

male rat. Fundam. Appl. Toxicol., 28(1):9-17.

National Heart, Lung, and Blood Institute, 2000. Morbidity & mortality: 2000 chart book on

cardiovascular, lung, and blood diseases. National Institutes of Health, Bethesda, MD.

NRC, 1983. Risk assessment in the federal government: managing the process. National

Research Council, Committee on the Institutional Means for Assessment of Risks to Public

Health, Commission on Life Sciences. National Academy Press, Washington, D.C.

NRC, 1999. Arsenic in drinking water. National Research Council, Committee on Toxicology,

Commission on Life Sciences, National Academy Press, Washington, D.C.

NTP, 1996. Sodium bromate (rats), CAS No. 7789-38-0. Study Number RDGT94007, NTIS#

PB96-190640. National Toxicology Program, National Institute of Environmental Health

Sciences, Research Triangle Park, NC.

NTP, 1998. Short term reproductive and developmental toxicity study of bromochloroacetic

acid (CAS No. 5589-96-8) when administered to Sprague-Dawley rats in the drinking water.

Study Number RDGT96001, NTIS# PB98-172414. National Toxicology Program, National

Institute of Environmental Health Sciences, Research Triangle Park, NC.

NTP, 1999. Final range finding report: Immunotoxicity of dibromoacetic acid in female

B6C3F1 mice. NTP #IMM98001, National Toxicology Program, National Institute of

Environmental Health Sciences, Research Triangle Park, NC.

NTP, 2000. Final range finding report: Immunotoxicity of sodium bromate in female B6C3F1

mice. NTP #IMM98004. National Toxicology Program, National Institute of Environmental

Health Sciences, Research Triangle Park, NC.

U.S. Census Bureau, 2000. Resident population estimates of the United States by age and sex.

April 1, 1990 to July 1, 1999 with short-term projection to July 1, 2000. Population Estimates

Program, Population Division, U.S. Census Bureau, Washington, D.C.
23

Ventura S.J., W.D. Mosher, S.C. Curtin, J.C. Abma, and S. Henshaw, 1999. Highlights of trends

in pregnancies and pregnancy rates by outcome: Estimates for the United States, 1976-96.

National vital statistics reports, vol 47 no 29. National Center for Health Statistics, Hyattsville,

MD.

Waller, K., S.H. Swan, G. DeLorenze, and B. Hopkins, 1998. Trihalomethanes in drinking water

and spontaneous abortion. Epidemiology, 9(2): 134-140.