HEALTH EFFECTS
LABORATORY
U S ENVIRONMENTAL PROTECTION AGENCY
Research Triangle Park, North Carolina
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THE ADVOCATE
The creation of the United States Environmental Protection
Agency in 1970 gives to the American people a single authority
to serve as their advocate for a livable environment. In its
creation, EPA was chartered to be a strong independent agency.
Its charges were clear. Mount a forceful integrated attack on
pollution; serve as an objective, impartial arbiter of environmental
matters; establish and enforce control standards.
Thus, the piecemeal approach to the environmental problems
of the nation were at last being met head on^problems that had,
in the past, so often inhibited progress, or worse, had merely
substituted one form of pollution for another.
Therefore, first and foremost, EPA was given teeth. Within
the limits of various statutory authorities, it was commissioned to
perform as a strong regulatory agency with the responsibility to
establish and enforce environmental standards. However, the
process of setting standards must begin with scientific research
which must supply answers to such basic questions as:
• Where do pollutants come from?
• How can they be identified and measured?
• What are their effects?
• How can they be controlled?
To supply comprehensive answers to these questions, the role
of research must be at least threefold. It must:
Tell us what specific level of a specific pollutant does to
human beings; to crops and other vegetation; to domestic
animals and wildlife; and to materials such as concrete,
steel, painted surfaces, and fabrics.
Establish threshold levels at which adverse effects might
be expected from environmental pollutants, alone or in
combinations.
Provide the basic scientific knowledge needed to safe-
guard public health and to balance the benefits of a
scientific product against the hazards it might impose on
the environment.
Therefore, the Office of Research and Development of EPA,
with its 15 laboratories, provides the essential scientific founda-
tion for the action required to improve environmental quality. In
building this foundation, evidence is gathered, not only from
internal research studies, but also from scientific and technical
advisory committees, from the scientific community, and from
industry.
The Health Effects Research Laboratory (HERL) at Research
Triangle Park (RTF), North Carolina is one of the 15 labs making
its all-important contribution to the molding and strengthening
of that foundation.
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HERL Scientists Conduct Biological Research
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The name of this organization is truly descriptive: the Health
Effects Research Laboratory. Through its coordinated, multi-
disciplinary research programs in epidemiology, in clinical studies,
and in toxicology, HERL is continually studying environmental
health problems—problems that would possibly affect the health
of the general public.
These studies address problems in air pollution, nonionizing
radiation, environmental carcinogenesis, and the toxicology of
pesticides and other chemical pollutants. The Laboratory de-
velops and revises air quality criteria documents on pollutants for
which national ambient air quality standards exist or are
proposed. It provides research data needed by the Agency to
make regulatory decisions on the registration of new pesticides,
or proposed suspension of those already in use. And, it conducts
research on hazardous and toxic materials, including the prepara-
tion of standards for nonionizing radiation.
Ten percent of the resources of HERL are used in providing
support to the Regional and Program offices of EPA. This
assistance is often in the form of testimony in court hearings and
in the preparation of position papers and affidavits to assist in the
enforcement of environmental standards.
While most of the facilities are located in the Research
Triangle Park, North Carolina, HERL has its Clinical Research
Facility at the University of North Carolina at Chapel Hill, and a
pesticide research field station in Wenatchee, Washington.
Organizationally, HERL consists of three staff offices and
four divisions with a total of approximately 350 employees. More
than 100 of the professional and technical staff hold advanced
degrees. And, 120 of the employees have worked in EPA since its
formation in 1970.
The total annual budget of the Laboratory s approximately
$25,000,000. Almost two-thirds of that amount is expended for
contracts, grants, and interagency agreements, complementing an
in-house onsite research program conducted by HERL employees.
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Pulmonary Function Data Are Collected for Epidemiological Study
RESEARCH ACTIVITIES
The Epidemiology program is nationwide in scope and is
designed to investigate relationships between environmental
quality and the health status of human populations. To accom-
plish this goal, studies are conducted in communities which are
selected to provide information about the health effects associ-
ated with exposure to specific pollutants or to groups of
pollutants as determined by air exposure data. In most studies,
community health information is collected from individuals and
families residing within two miles (3.2 km) of an air monitoring
station. A total of 22 fixed stations and 5 mobile units are
included in the system. These stations provide data which
estimate exposure levels of residents in the surrounding neighbor-
hood.
Estimates of exposure-response relationships and the docu-
mentation of changes in health status, coincident with temporal
changes in environmental quality, are the major objectives of the
program. The ability to accomplish these objectives depends upon
the valid quantification of health parameters as well as upon the
precise measurement of levels of exposure.
Studies designed to document the benefits of pollution
control are conducted across the country in areas of improving air
quality. Other studies will attempt to measure the health
implications of the planned shift by power plants and industry,
from low- to high-sulfur fuels, and from gas or oil to coal.
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Clinical studies, which address the effects from pollutant
exposure, are conducted in several areas of research in our
facilities located on the campus of the University of North
Carolina at Chapel Hill. These facilities include:
• A neurobehavioral laboratory in which the psycho-
physiological effects of air pollutants are studied
• A microbiology laboratory investigating the effects of
pollutants on the human immune system
• A laboratory equipped to study metabolic and endo-
crine changes associated with environmental stress
• A laboratory equipped to study the health effects of
pollutants on pulmonary and cardiovascular perfor-
mance
In addition, two research programs identified by the acronyms
CLEANS (Clinical Laboratory Evaluation and Assessment of
Noxious Substances) and CLEVER (Clinical Laboratory Evalua-
tion and Validation of Epidemiological Research), are now under
way. With these facilities, HERL now has the most comprehen-
sive resources available anywhere for conducting clinical studies.
The CLEANS project will include an online, computerized,
physiologic data acquisition system serving two large controlled-
environment laboratories. In these labs, volunteers can be
exposed for extended periods of time to the same air pollutant
levels found in urban areas. These facilities will allow the Clinical
Studies Division to perform research relating air pollutants to a
wide range of physiological responses—and for much longer
periods than could be observed in the past.
(Left) Biochemistry Laboratory
(Right) Exposure Facility to Study the
Health Effects of Pollutants on Pulmonary
and Cardiovascular Performance
Neurobehavioral Research
Microbiology Laboratory
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Each of these two laboratories contains the most sophisti-
cated instrumentation available for assessing the health status of
the subjects. Especially important are instruments for measuring
the functioning of the heart and lungs before, during, and after
exercise. And, due to the complexity of this instrumentation, the
large amount of data that is acquired, and the need for timely
reports, most of the testing is conducted using a computerized
data acquisition system. Through interaction with the computer,
medical technicians and research physicians will be able to
monitor and direct the studies.
These controlled environmental laboratories, which operate
over a wide range of temperature and humidity conditions, can be
programmed to simulate the desired pollution diurnal profile,
from "clean" to "dirty." Both laboratories can provide carefully
controlled levels of carbon monoxide, sulfur dioxide, nitrogen
dioxide, nitric oxide, and ozone—either singly or in any combina-
tion. One of the laboratories will also model environments
polluted by fine particulate aerosols, such as nitrate and sulfate
compounds. To provide maximum flexibility and reliability, these
environmental conditions are also under computer control.
Studies of the health status of populations have provided
much of the available information relating environmental factors
to human health. These studies, however, are filled with
difficulties in quantifying exposure, and in determining subtle
alterations in health status, from one geographical location to
another.
HERL has responded to these problems with the development
of the mobile CLEVER program. This program will permit, in the
field, the verification of epidemiological research, using sensitive
measurements of cardiovascular and pulmonary functions. Two
mobile laboratories, which contain the same physiologic and
computerized systems used in the CLEANS program, can travel
CLEANS Environmental Exposure Facility
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Interior of Mobile CLEVER Laboratory
to areas in which pollutant levels are of concern and can, on
location and over an extended period of time, perform extensive
evaluation of the health status of selected populations. In
addition to the standard cardiopulmonary function measure-
ments, the mobile laboratories are equipped for the collection of
biological samples for later analysis of the pollutant burden.
Nonionizing Radiation Studies
The health hazards, which may result from exposure to the
electromagnetic radiation of radio and microwave transmissions
in the environment, are relatively unknown. To expeditiously
investigate the potential of these hazards, a multi-agency program
has been organized. This effort, which is coordinated by the
White House Office of Telecommunications, is identified as
"Program for Control of Electromagnetic Pollution of the
Environment: The Assessment of Biological Hazards of Non-
ionizing Electromagnetic Radiation."
HERL is making an important contribution to that program.
In its investigations, whole animals, and cellular, subcellular, and
molecular preparations are used to determine the possible effects
on the genetic, biochemical, immunological, teratological, and
neurobiological functions. These studies are also designed to
establish the exposure levels at which these effects are elicited
and to delineate the mechanisms of physical alterations. Results
will provide a data base for the promulgation of standards
governing the allowable environmental level of this type of
radiation.
Microwave Exposure Chamber
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Teratological Investigations Are Conducted
Toxic Substances Research
Giemsa-stained, Human Skin Fibroblasts are Shown
(Magnified) After 1-Day Exposure in Control Culture
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lexicological Studies
Comprehensive biomedical studies are under way to evaluate
the actual and potential biological effect of the major air
pollutant gases and particulates. Pollutants emphasized include
sulfuric acid and sulfates, ozone, nitrogen dioxide, organic
chemicals and metals. This work is carried on through an
integrated program employing whole animal and in vitro models.
The influence of sulfuric acid and various sulfates is being
studied in isolated cells, perfused lung tissue, and in whole
animals. To pursue these studies, a dynamic reaction chamber to
furnish exposure facilities simulating natural atmospheres has
been constructed.
Each year several hundred new chemicals are introduced into
commercial use, even though, in most cases, their potential health
and ecological effects are not known. Legislation controlling the
use of toxic substances is an important aspect of regulating their
introduction into the environment. Rather than emphasis on
pollutants already in air and water, this type of legislation is
based on understanding the flow of potentially toxic substances
through the entire range of activity, from extraction or synthesis,
to production, consumer use, and final disposal. Of particular
concern are the potentially deleterious health effects resulting
from long-term exposure to low concentrations of these chem-
icals, alone or in combination.
Therefore, HERL has an ever-expanding role in assessing the
toxicity of synthetic organic compounds, metals, and metallic
compounds, and in developing sensitive analytical methods for
measuring the level of these toxic substances in the environment
and in organic material.
Mutagenesis Research Is Conducted Using in vitro Test Systems
Studies of the relative toxicity of mercury, lead, cadmium,
zinc, chromium, nickel, manganese, and various sulfate com-
pounds have been conducted using pulmonary macrophages and
human fibroblasts in vitro. The influence of these materials on
membrane and cellular transport mechanisms and on cell life span
is being investigated.
Pulmonary carcinogenesis research is accomplished using
intratracheal instillation of a known carcinogen (benzo[a] pyrene)
alone or in combination with metallic oxides. Chemically
characterized crude particulate materials collected from the
ambient air and the interaction of this material with NO2 and OB
in the induction and/or alteration of pulmonary neoplastic
response in animals is being investigated as well.
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An in vitro toxicity screening system using rabbit alveolar
macrophages is now fully developed for estimating the relative
toxicity of particulate air pollutants. This system .provides
complete dose-response data on cell number, viability, metabo-
lism, and phagocytic activity. And, the system is currently being
employed to estimate the relative toxicity of particulates in air
samples from stationary sources. An additional system, employ-
ing rapidly dividing human lung fibroblasts, has been developed
to test for compounds that inhibit cellular biosynthetic activities.
Pesticide Studies
Research is carried out at HERL-RTP to assess the potential
human health hazard of pesticides. Most efforts are focused on
toxicity studies using animal model systems, on field studies to
address "real world" exposure problems, and on analytical
methods developed to improve the sensitivity and specificity of
residue analysis in various environmental media. Development of
new chemical and biological pesticides by industry and the
recognition of previously unknown hazards associated with
pesticides in current use, will continue to require new knowledge
of pesticide toxicology and chemistry.
With the discovery of the toxic contaminant 2,3,7,8-tetra-
chlorodibenzo-p-dioxin (TCDD) in formulations of the herbicide
2,4,5-T, the results of active research began to detect and identify
other potentially toxic contaminants in commercial formulations.
During the chemical synthesis of pesticide compounds, there is
the possibility that unwanted toxic products may also be formed.
To prevent the future release of potentially toxic materials into
the environment, both theoretical studies of the synthesis
processes and the laboratory analysis of typical pesticide com-
pounds are under way.
Technology has developed new generations of pesticides that
use more effective chemical formulations. And techniques have
been evolved for controlled release through microencapsulation,
and for biological insect control agents, such as insect pathogens
and synthetic juvenile hormones. Toxicological research is under
way with the newly developed viral insect pathogens to ascertain
whether adverse acute or chronic effects can be associated with
their use. The determination of the potential of these organisms
to undergo mutation which might render them pathogenic to man
or domestic animals is of special concern.
The search for methods of detecting early exposure to
pesticides, before actual symptoms of poisoning are evident, has
been going on for many years. EPA has developed two techniques
Pesticides Inhalation Exposures
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that show promise: a chemical method for detecting organically
bound phosphate residues in urine after exposure to organo-
phosphate pesticides; and, a neurophysiological method to detect
subtle changes in brain-wave patterns after pesticide exposure.
Tests to estimate the level of exposure of workers and
residents to pesticides under actual conditions of field use are also
being developed. Concurrently, emphasis is being given to
attempts to validate short-term animal tests, such as bioassay
procedures, as screeening methods for the more traditional, long
term animal tests.
Animal Husbandry
HERL maintains eight species of laboratory animals at its
Research Triangle Park facility, including subhuman primates.
The • animal care staff has comprehensive expertise in the
approved techniques of animal husbandry, intubation, parenteral
dosing, breeding colony maintenance, and timed mating tech-
niques.
Statistics and Data Management
HERL researchers and program managers work closely with a
highly trained staff of statisticians, programmers, and systems
analysts. These specialists, who participate in the design of studies
for the entire Laboratory, also process and analyze resulting data.
Technical and administrative data bases and the software neces-
sary to use and analyze these data are developed and maintained.
The staff develops statistical theory and data analysis techniques
for environmental health effects research studies. In summary,
the staff provides the vital statistical and data processing expertise
so necessary to the effective functioning of a coordinated HERL
research program.
Weighing and Tagging Experimental Animals
Statistician Uses Computer Terminal for Plotting Health Data
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Special Document Preparation
HERL provides documentation which critically reviews,
evaluates, compares, interprets, and summarizes pertinent litera-
ture and reports. This documentation leads to the:
• revision of existing criteria documents or the prepara-
tion of additional scientific and technical assessment
reports concerning air quality effects of currently
nonregulated environmental pollutants,
• identification of the need for additional research
required to produce adequate criteria for issuing or
revising standards, and preparation of briefing reports,
addressing new areas of environmental concern that
are not already part of the existing program.
The latest available scientific information on the sources,
prevalence, and manifestations of recognized air pollutants are
compiled in Criteria Documents. Most importantly, these criteria
describe the effects that have been associated with, or may be
expected from, an air pollutant level in excess of a specific
concentration for a specific time period. Such effects involve a
detriment to the health and well-being of humans and animals.
Other effects include visibility reduction, damage to materials,
vegetation damage, and nuisance aspects. The Air Quality Criteria
provide a basis for national ambient air quality standards.
Scientific and technical documentation serves two very
important purposes. To summarize the scientific knowledge base
for administrative decisions regarding the need and strategy for
control and to provide important input for research and
development program plans, scientific and technical assessment
reports are prepared. In view of their widespread distribution,
these documents, which are prepared in consultation with other
EPA laboratories, also serve as an important communications link
with other EPA offices, other agencies, and with special-interest
groups. In order to serve this broad audience, these must be
functional documents, clearly and concisely written.
INTERNATIONAL RESEARCH PROGRAM
In recognition of the global significance of environmental
pollution, a wide variety of international activities are carried out
as a logical extension of the entire HERL program.
Some of the major international activities of HERL include
involvement with the World Health Organization, the Commission
of the European Countries, and with the Pan American Medical
Association. Also HERL-RTP participates in Bilateral Environ-
mental Agreements with the Federal Republic of Germany,
Japan, and the USSR. In addition, HERL serves as a consultant to
the Israel Binational Foundation, and participates in several
Special Foreign Currency Projects.
As a widely recognized source of expertise in environmental
research, HERL often provides briefings for international sci-
entists concerning areas of mutual interest, and in addition it
responds to requests for information and assistance. Responding
to these requests is recognized as not only a means of assisting
other countries to reach their pollution abatement goals and of
promoting international good will; response also opens up
valuable new insights that will speed the progress of our own
country to its goals of improved environmental quality.
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Envfconmenta! Protection Agonoy
EegLon V, Library
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