Health Effects Research Laboratory
Midyear Report
F.Y. - 77
Research Hiangle Rirk, North Carolina
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Note: This report is for informational purposes
only. Data contained in this report must be
considered provisional. Mention of trade names
or commercial products in this publication does
not constitute endorsement or recommendation
for use by the Environmental Protection Agency.

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Health Effects Research Laboratory
Midyear Report
FY. - 77
Prepared
by
The Program Operations Office
U.S. ENVIRONMENTAL PROTECTION AGENCY
Health Effects Research Laboratory
Research Triangle Park, North Carolina 27711
August 1977

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FOREWORD
The U.S. Environmental Protection Agency's Health Effects Research Laboratory located at Research
Triangle Park, North Carolina conducts an extensive research program to evaluate the human health impli-
cations of environmental factors related to industrialized society. The purpose of this research is to provide
information necessary to formulate environmental regulatory policies to protect or improve public health
and welfare while at the same time enhancing the nation's productivity. To this end, the Laboratory con-
ducts a comprehensive program in toxicology, epidemiology, and research on human subjects under con-
trolled laboratory conditions. Nearly one-half the Laboratory's resources are devoted to evaluating the
hazards of air pollution which constitutes the most ubiquitous and costly environmental problem. Nearly
one-fourth of our research program is directed toward establishing guidelines for the safe use of pesticides
which are of crucial importance to the nation's agricultural industry. Other programs address the problems
of electromagnetic irradiation—such as that from radio, television, and radar—environmental carcinogenesis,
and the myriad of new chemicals and potentially toxic materials introduced into our environment.
This Fiscal Year 1977 Midyear Report is intended to describe for you the relative effort and resources
being brought to bear on these problems and the degree of progress being made. It is intended to inform
you in a general way of the nature of the research we conduct and provide you the opportunity to seek
more detailed answers to your specific questions.
JOHN H. KNELSON
Director
Health Effects Research Laboratory
ii

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CONTENTS
Foreword.
1.	Introduction	1
Functions	1
Location	1
Organization	1
Status of funds — Table 1	1
Research activities	3
Epidemiology program	3
Clinical studies	4
CLEANS	5
CLEVER	5
Nonionizing radiation studies	7
Toxicological studies	8
Pesticide studies	10
Animal husbandry	12
Statistics and data management	13
Special document preparation	14
International research program	15
2.	Major Accomplishments	17
Ozone exposures relate to adverse health effects	19
Certain air quality standards may allow excessive health risk	20
Correlation found between air-lead levels and traffic densities in Dallas 	21
National environmental specimen bank will allow retrospective analyses	22
Seven pesticides give mutagenic response	23
Chronic exposure of rats to microwave radiation may alter immune system		24
Increase in exencephaly after micron exposure 	25
3.	Research Objectives	27
Air Programs	28
Regulated air pollutants	29
Nonregulated air pollutants	32
Regulated and nonregulated pollutants associated with transportation	34
Criteria documents	35
Effects of Pesticides and Toxic Substances	36
Pesticides	37
Pesticides (Substitute Chemicals Program)	39
Total quality assurance program for pesticide residue measurements	41
Toxic substances	42
National Center for Toxicological Research	43
Health Effects of Exposure to Radiant Energy	44
Radiant Energy	45
Heavy Metals	46
Nonpesticide organic and inorganic substances reaching man	47
Pollutants Associated with Energy Development	49
Health effects from pollutants associated with energy development	50
Environmental assessment interface and research studies	52
Carcinogens	53
Contribution of carcinogens to cancer incidence in the general population	54
Bibliography	55

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Ten percent of the resources of the Health Effects
Research Laboratory (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.
Location — While most of the facilities are located in
the Research Triangle Park, North Carolina, HERL has its
Clinical Research Facility at the Medical Center of the
University of North Carolina in Chapel Hill and a pesticides
research field station in Wenatchee, Washington.
Organization — HERL consists of the immediate Office
of the Director, three staff offices, and four divisions, with a
total of approximately 350 employees. More than 100 of
the professional and technical staff hold an advanced degree.
Also, 120 of the employees have worked in EPA since its
formation in I970.
The total annual budget of the Laboratory is approxi-
INTRODUCTION	mately $27,500,000. Almost two-thirds of that amount is
expended for contracts, grants, and interagency agreements,
complementing an in-house research program which is con-
ducted onsite by the staff of HERL.
Tabic 1. HEALTH EFFECTS RESEARCH LABORATORY - STATUS OF FUNDS -
FUNCTIONS
The name of the Health Effects Laboratory of the En-
vironmental Protection Agency, located at Research Triangle
Park, N.C., well describes its function. Through coordinated,
multidisciplinary research programs in epidemiology, in
clinical studies and in toxicology, the Health Effects Research
Laboratory (HERL) is continually studying environmental
health problems, seeking solutions which would benefit the
health of the general public.
These studies address problems in air pollution, non-
ionizing radiation, environmental carcinogenesis, and the
toxicology of pesticides and other chemical pollutants. The
Laboratory develops and revises air quality criteria docu-
ments 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 the proposed suspension of
those already in use, and conducts research on hazardous and
toxic materials, including the preparation of standards for
nonionizing radiation.


Extr

Irv

P.E.*
A.P.*
Budgat
Committed
Budgat
Committed
1AAM1
Program Manapmant
Trmportatton
CriKrla
Noncrltaria
NonpaitlcMa*
CardnoganMit
Critarla Oocumaoa
•36.0
3.3410
1,064.6
263 3
240.0
406.0
622.3
1.621.6
1,261.0
263.2
130.0
00.2
8110
640.0
1,687.7
1,306.0
722.6
236.0
866.0
260.3
1,668.1
1,336.3
672.3
200.0

P.E. TOTAL
6.830.0
4.068.2
6,314.1
4,800.6
1EA816
Paatiddaa
Sutoatituta
Chamteali
027.4
1.260.0
710.7
703.0
2,782.6
800.0
2,004.0
386.6

P.E. TOTAL
2.177.4
1,402.7
3,262.8
2.470.6
1FA828
Radiant Enar«y
46.3
16.3
721.7
678.6
1HA830
National Contar for
Tax Zoological Raaaarch
4,000.0



1H0821
Quality Aaaurane*
110.0
110.0
340.0
223.6
1 LASSO
Toxic Sutatancai
4430
281.0
477.0
172.2
1NE823
Environmental
Aawmant
66.0

46.0
.6
1NE826
Enargy
3.734.0
2,308.4


XM1827
ERDA
NIH
7.7
7.7
80.0
10.0

SUB-TOTAL
17.416.3
8.171.3
10.140.4
8.062.8
iGAett
WHO


32.8
7.7

TOTAL
17,416.3
8.171.3
10,173.0
6,070.6
* P.E. - Program Elamant
t A. P. - fcoompllthmant flan
1

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HEALTH EFFECTS RESEARCH LABORATORY
Director
Dr. John Knelson
Deputy Director
Dr. Robed E. Lee
STATISTICS AND DATA
MANAGEMENT OFFICE
Dr. William Nelson
PROGRAM OPERATIONS
OFFICE
	Mr. Mike Berry
CRITERIA ANDSPECIAL
STUDIES OFFICE
Mr. OrinStopinski
EXPERIMENTAL BIOLOGY
DIVISION
Dr. Daniel Cahill
CLINICAL STUDIES
01 VISION
Dr. John Knelson (Act.)
POPULATIONS STUDIES
DIVISION
Or. Robert Horton (Act.)
ENVIRONMENTAL TOXICOLOGY
DIVISION
Dr. William Durham	
Toxic Effects 8ranch
Mr. August Curley
Bioengineering
Branch
Mr. George Anderson
Exposure Assessment
Branch
Or. David Mage
Research Services
Branch
Mr. Walter Crider
Developmental Biology
Branch
Dr. William Kirk
Biochemistry
Branch
Or. Mike Waters
Analytical Chemistry
Branch
Dr. Edward Oswald
Systems Engineering
Section
Dr. Marvin Hertz
Chemical Characterization
Section
Or. Robert Lewis
Data Management
Staff
Mr. Gerald Nehls
Pesticides and Organic Chemicals
Evaluation Section
Dr. Diane Courtney
Program Administration
Staff
Ms. Ann Akland
Metabolic Effects
Section
Dr. Stephen Nesnow
Statistics
Staff
Mr. John Creason
Cellular and Molecular Effects
Evaluation Section
Dr. John Allis
Technical Services
Staff
Mr. Wayne Fulford
Multiple-Stress Evaluation
Section
Mr. John Laskey
Measurement Technology
Section
Mr. Robert Burton
Metabolic Pathways
Section
Dr. Robert Chadwick
Inhalation Toxicology
Section
Vacant
Field Logistics
Section
Mr. David Hinton
Pathology & Microbiological
Studies Section
Dr. Thomas Scotti
Methods Development
Section
Or. Robert Moseman
Quality Assurance
Section
Mr. Jack Thompson
Acute & Chronic Studies
Section
Dr. Larry Hall
Special Studies and Research
Support Section
Or. James Wright
Cellular Biology
Section
Or. Joellen Huisingh
Air Pollutants
Branch
Dr. Carl Hayes
Clinical Pathology
Branch
Dr. George Goldstein
Biomedical Research Branch
Dr. Donald Gardner
Special Pollutants Branch
Dr. Carl Hayes (Act.)
Neurobiology Branch
Dr. Joe Elder
Animal Care
Branch
Dr. Donald Hinkle
Physiology
Branch
Dr. Edward Haak
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RESEARCH ACTIVITIES
Pulmonary function data are collected for
epidemiological study
Studies designed to document the benefits of pollution
control are conducted across the country in areas where the
air quality is improving. 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.
THE EPIDEMIOLOGY PROGRAM
This program is nationwide in scope and is designed to
investigate relationships between environmental quality and
health status of human populations. To accomplish this goal,
studies are conducted in communities which are selected to
provide information about the health effects associated with
exposure to specific pollutants or to groups of pollutants as
determined by air exposure data. In most studies, commu-
nity health information is collected from individuals and
families residing within two miles (3.2 km) of an air monitor-
ing station. A total of 22 fixed stations and 5 mobile units
are included in the system. These stations provide data
which estimate levels of pollutants to which residents in the
surrounding neighborhood are exposed.
Estimates of exposure-response relationships and the
documentation of changes in health status coincident with
temporal changes in environmental quality, are the major
objectives of this 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.
Mobile community health air monitoring vehicle
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A neurobehavioral laboratory in which the
psychophysiological effects of air pollutants
are studied
CLINICAL STUDIES
These studies address the effects from pollutant
exposure, and are conducted in several research areas in our
facilities located on the campus of the University of North
Carolina at Chapel Hill.
A laboratory equipped to study metabolic and
endocrine changes associated with environmental
stress
A laboratory to study the health effects of
pollutants on pulmonary and cardiovascular
performance at rest and during periods of graded
exercise
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A microbiology laboratory investigating the
effects of pollutants on the human immune
system
In addition, two research programs are now underway.
They are identified by the acronyms CLEANS (Clinical
Laboratory Evaluation and Assessment of Noxious Sub-
stances) and CLEVER (Clinical Laboratory Evaluation and
Validation of Epidemiological Research). With these facilities,
HERL now has the most comprehensive facilities available
anywhere for conducting clinical environmental studies.
The CLEANS project includes an online, computer-
ized, physiologic data acquisition system, serving two con-
trolled-environment laboratories where human volunteers can
be exposed for extended periods of time to air pollutant
levels closely simulating those found in urban areas. These
facilities allow the Clinical Studies Division to perform
research relating air pollutants to a wide range of physio-
logical parameters — and for much longer periods than could
be observed in the past.
Each of these two laboratories contains the most
sophisticated instrumentation available for assessing the
health status of the subjects. Especially important are instru-
ments for measuring the functioning of the heart and lungs
before, during, and after exercise. Because of the complexity
of this instrumentation, as well as 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 are able to
monitor and direct the studies.
These controlled environmental laboratories, which
operate over a wide range of temperature and humidity con-
ditions, 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 oxides and ozone—
either singly or in any combination. 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 con-
ditions are also under computer control.
Studies of the health status of populations have pro-
vided much of the available information relating environ-
mental factors to human health. These studies, however, are
filled with difficulties in quantifying exposure and in de-
termining 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 onsite 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 to areas in which pollutant levels are of
concern and can, in the field and over an extended period of
time, perform extensive evaluation of the health status of
selected populations. In addition to the standard cardio-
pulmonary function measurements, the mobile laboratories
are equipped for the collection of biological samples for
later analysis.
Clinical Research Facility at Chapel Hill, N.C.
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CLEVER vehicle will be used in conjunction with
CHAMP vehicle in epidemiological investigations
Volunteer on treadmill in one of the CLEANS
controlled environmental chambers
CLEANS control console and controlled environmental laboratory
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NONIONIZING RADIATION STUDIES
The health hazards which may result from exposure to
the electromagnetic radiation of radio and microwave trans-
missions in the environment are relatively unknown. To in-
vestigate the potential of these hazards expeditiously, a
multiagency program has been organized. This effort, which
is coordinated by the White House Office of Telecommunica-
tions, is identified as "Program for Control of Electromagnetic
Pollution of the Environment: The Assessment of Biologi-
cal Hazards of Nonionizing Electromagnetic Radiation."
V

Experimental Biology Division microwave
exposure facility
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, immuno-
logical, teratological, and neurobiological functions. These
studies are also designed to establish the exposure levels at
which these effects are elicited and to delineate the mech-
anisms of physical alterations. Results will provide a data
base for the promulgation of standards governing the allow-
able environmental level of this type of radiation.
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Toxicity screening
TOXICOLOGICAL 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 in-
clude sulfuric acid	and sulfates, ozone (Og), nitro-
gen dioxide (N02), 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.
Of particular concern are the potentially deleterious
health effects resulting from long-term exposure to low con-
centrations of new chemicals, alone or in combination. Each
year several hundred new chemicals are introduced into com-
mercial 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 regu-
lating 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.
Therefore, HER L 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 concentration of these toxic sub-
stances in the environment and in organic material.
Studies of the relative toxicity of mercury, lead, cad-
mium, zinc, chromium, nickel, manganese, and various
sulfate compounds 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 lifespan 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 NOj and Og in the induction and/or altera-
tion of pulmonary neoplastic response in animals, is being
investigated as well.
An in vitro toxicity screening system using rabbit
alveolar macrophages is now fully developed for estimating
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the relative toxicity of particulate air pollutants. This system
provides complete dose-response data on cell number,
viability, metabolism, and phagocytic activity. Also, the
system is currently being employed to estimate the rela-
tive toxicity of particulates in air samples from stationary
sources. An additional system, employing rapidly dividing
human lung fibroblasts, has been developed to test for
compounds that inhibit cellular biosynthetic activities.
Macrophage before and after exposure to air pollutant
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release of potentially toxic materials into the environment,
both theoretical studies of the synthesis processes and
the laboratory analysis of typical pesticide formulations
are under way.
Technology has developed new generations of
pesticides that use more effective chemical formulations,
such as the controlled release of pesticides through micro
encapsulation. Also, biological insect control agents, such
as insect pathogens and synthetic juvenile hormones have
Investigation of whether or not new viral
insect pathogens cause adverse health effects
PESTICIDES 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 sys-
tems, on field studies to address "real world" exposure
problems, and on analytical methods developed to improve
the sensitivity of residue analysis in various environmental
media. Development of new chemical and biologic pesti-
cides by industry and the recognition of previously unknown
hazards associated with pesticides in current use, will con-
tinue to require new knowledge of pesticide toxicology and
chemistry.
With the discovery of the toxic contaminant 2,3,7,8-
tetrachlorodibenzo-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 products. During the chemical synthesis of
pesticide compounds, there is the possibility that unwanted
toxic products may also be formed. To prevent the future
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been developed. 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 specific
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 that show promise: a chemical
method for detecting organically bound phosphate residues
in urine after exposure to organophosphate 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 screening methods
for the more traditional long-term animal tests.
Pesticide inhalation exposures
Rochester exposure chambers
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Eight species of laboratory animals are maintained
at the HERL—RTP 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 techniques.
ANIMAL HUSBANDRY
Weighing and tagging experimental animals
Tatooing monkey
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HERL researchers arid 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 admin-
istrative data bases, and the software necessary to use and
analyze these data, are developed and maintained. The staff
also develops statistical theory and data analysis techniques
for environmental health effects research studies. In sum-
mary, the staff provides the vital statistical and data pro-
cessing expertise so essential to the effective functioning
of a coordinated HERL research program.
Data analysis
STATISTICS AND DATA MANAGEMENT
Data processing
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The latest available scientific information on the
sources, prevalence, and manifestations of recognized air
pollutants is compiled in Criteria Documents. Most impor-
tantly, these criteria describe the effects that have been
associated with, or may be expected from, an air pol-
lutant 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
and vegetation, 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 know-
ledge base for administrative decisions regarding the need
and strategy for control; and to provide important input
for research and development program plans, as well as
scientific and technical assessment reports. In view of their
widespread distribution, these documents, which are pre-
pared in consultation with other EPA laboratories, also
serve as an important communications link with other EPA
offices, other agencies, ahd with special-interest groups. In
order to serve this broad audience, these must be functional
documents, clearly and concisely written.
SPECIAL DOCUMENTATION PREPARATION
HERL provides documentation which critically
reviews, evaluates, compares, interprets, and summarizes
pertinent literature and reports. This documentation leads
to the:
• revision of existing criteria documents
or the preparation of additional scientific
and technical assessment reports concerning
air quality effects of currently nonregulated
environmental pollutants.
Criteria document revision
• 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.
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gis qr>(
HERL participates in US—USSR Bilateral
Environmental Agreement
INTERNATIONAL RESEARCH PROGRAM
In recognition of the global significance of environ-
mental 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
(WHO) and the Commission of the European Communities.
Also, HERL-RTP participates in Bilateral Environmental
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 environ-
mental research, HERL often provides briefings for inter-
national scientists concerning areas of mutual interest, and in
addition it responds to requests for information and assis-
tance. Responding to these requests is recognized not only
as a means of assisting other countries to reach their pol-
lution abatement goals and of promoting international good
will, but also as providing valuable new insights that will
speed the progress of our own country to its goal of
improved environmental quality.
The following pages of this report provide a brief
summary of the research objectives and highlights of the
Laboratory's accomplishments for the first half of Fiscal
Year 1977. More detailed information concerning indi-
vidual research projects may be obtained by requesting
from the HERL's Technical Information Center (MD-51),
Research Triangle Park, North Carolina 27711, copies of
the publications listed in the Bibliography of this report.
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16

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MAJOR ACCOMPLISHMENTS
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OZONE EXPOSURES RELATE TO ADVERSE
HEALTH EFFECTS
spirometry, maximum expiratory flow-volume curves, and
body plethysmographic measurement of airway resistance
and lung volumes. Changes in pulmonary function after 1
and 2 hours of ozone were compared to values obtained at
the same times during a control 2-hour exposure to clean
air. Most subjects exposed to ozone complained of cough,
substernal chest pain, shortness of breath, and a decreased
ability to maximally inspire. A few subjects continued with
symptoms several hours post exposure. After 1 hour of
ozone, maximal midexpiratory flow rate (MMFR), flow
at twenty-five percent and fifty percent of vital capacity
(V25 and VJ0), peak expiratory flow rate (PEFR), forced
vital capacity (FVC), and forced expired volume in 1 second
(FEVj), and inspiratory capacity (IC) were significantly
decreased. After 2 hours of ozone exposure, decreases in
these measurements were even greater, with the most marked
change being a 35% reduction in mean MMFR compared to
control values. Even though considerable individual variation
in response was noted, it is concluded that a 2-hour 0.6 ppm
ozone exposure, when coupled with moderate exercise, has
a significantly detrimental effect on pulmonary function in
healthy young males.
Pulmonary function study
Atmospheric photochemical reactions increase the
oxidant content of the atmosphere, particularly over urban
and industrialized areas. Of the total oxidant formed, as
much as ninety percent may be ozone. What effect does
ozone in concentrations approximating those occurring
in the Los Angeles Basin have on health? Recent investi-
gations conducted by a Clinical Studies Division research
team indicate that exposure to 1200 Aig/m (0.6 ppm)
ozone for two hours, coupled with moderate exercise,
produces significant pulmonary complaints as well as sig-
nificant decrements in pulmonary function.
This finding was established by exposing thirty healthy,
nonsmoking male subjects to 1200/ig/m (0.6 ppm) ozone
for two hours in an environmental chamber. Each subject
was seated at rest except for two 15-minute exercise
periods on a bicycle ergometer. The exercise was sufficient
to approximately double the resting heart rate. Subjects
were asked to report any symptoms that occurred during the
course of the chamber exposures and daily thereafter for the
followup period. Pulmonary function studies included
These adverse effects of ozone on pulmonary
function might be even more detrimental to the welfare
of those who are not in good health. The large fraction of
the population with chronic lung disease would probably
be most sensitive to these adverse effects. Based on this
study which confirms earlier similar studies, to assure
protection of the total population, 0.6 ppm ozone, even
for 1 hour, is unacceptably high as an alert level.
19

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CERTAIN AIR QUALITY STANDARDS MAY
ALLOW EXCESSIVE HEALTH RISK
The concentration of nitrogen dioxide (NC^) in a
polluted atmosphere is subject to wide variation, depending
upon the peak traffic load, the industrial productivity, and
various meteorological influences. This variation generally
results in a low basal atmospheric concentration of NC^,
upon which is superimposed higher peaks, usually of short
duration and irregular occurrence. This variation in the
mode of exposure could play an important role in the
determination of the toxicological effect of NC^.
Investigators in the Biomedical Research Branch
used continuous and intermittent animal exposure studies
to determine the relationship between biological response
and length of exposure to various concentrations of NC^-
As the concentration decreased, the slope of the regression
line decreased. After adjusting for total differences (con-
centration x time) the response for the two exposure modes
was essentially the same. When a constant (dose) level was
employed, a short-term exposure to a high concentration
produced a greater effect than exposure to a lower concen-
tration administered over a longer period. Using these
curves, the relationship between level of effect, concentra-
tion, and time was determined. Results of these studies
indicate that the frequency and amplitude of short-term
peaks are of significance even though the exposure is
interrupted with periods of zero concentration of NC^.
Consequently, air quality standards that do not account for
the frequency and amplitude of such spikes may allow
excessive risk to human health.
NC>2 exposure facility
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Most lead in the air we breathe results from the
burning of gasoline containing tetraethyl lead
CORRELATION FOUND BETWEEN
AIR-LEAD LEVELS AND TRAFFIC
DENSITIES IN DALLAS
Severe exposure to lead is an established health hazard.
However, the effects of exposure to low levels of lead for
long periods of time are not well understood. More than
ninety percent of the lead in the air we breathe results from
the burning of gasoline containing tetraethyl lead. There-
fore, scientists at the Southwest Research Institute, under a
contract monitored by the Population Studies Division,
conducted a study in Dallas designed to determine the
absorption of lead by people when exposed to automobile
emissions of lead.
Selection of participants for this study was based
upon strict criteria which eliminated anyone whose
blood-lead level was affected by exposure to sources of
lead other than automobile emissions and the data were
analyzed to take into consideration the factors of age and
sex. The degree of absorption of lead by participants was
determined by measuring blood-lead concentrations and
blood-FEP (free erythrocytic protoporphyrin).
Selected household samples (water from kitchen
tap, paint from the interior and exterior surfaces of
residences, 28-day indoor dust samples and window sill
wipes) were also measured for lead content to eliminate
them as possible sources of lead for the participants and to
only correlate their lead concentration with traffic densities.
No correlation was found between blood-lead levels of
participants and different traffic densities.
In addition, outside environmental samples were
analyzed for lead. These included soil from participants'
residences, outdoor dust from selected sites in the study
area, and air particulate matter from streets where par-
ticipants lived having different traffic densities. Increased
soil-lead content with increased traffic density was found,
and soil character was found to favor lead retention. No
correlation was found between outdoor dust lead and
traffic density. However, a small but statistically significant
relationship was found between increased levels of lead in
the air and increasing traffic densities.
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natural background pollution levels from levels attributable
to man-made pollution. This will be useful in determining
whether or not present pollution control techniques are
adequate to prevent increased accumulation of environ-
mental pollutants in the general population. It will also
serve as a pollution warning system by providing for real-
time analysis of a fraction of the collected specimens,
thereby identifying pollutant problems in specific parts of
the world as they first emerge. Storing the remainder of the
collected specimens will permit analysis of today's specimens
using tomorrow's more sensitive chemical methods. This
retrospective capability will allow tissue burden patterns to
be more confidently compared with fluctuations in mor-
bidity to test hypotheses dealing with the etiology and
aggravation of disease.
NATIONAL ENVIRONMENTAL SPECIMEN
BANK WILL ALLOW RETROSPECTIVE
CHEMICAL ANALYSES
Some chemicals are an essential part of our lives;
however, others can be deadly. Two chemicals commonly
used to make a variety of consumer goods—asbestos and
vinyl chloride-caused cancer in workers some twenty to
thirty years after they were exposed to these substances.
These are examples of discoveries made possible, in part,
because scientists have developed more sensitive, accurate
methods for detecting and measuring trace chemicals present
in low concentrations in food, tissues, water, and air. Are
there other apparently harmless chemicals present in our
environment which may prove to be health hazards?
Tissue will be analyzed using the most sophisticated
instrumentation
Finding the answer to this question is the major reason
that the Environmental Protection Agency (EPA), the
National Bureau of Standards (NBS), and the National
Science Foundation (NSF) are studying the feasibility of
establishing a National Environmental Specimen Banking
System.
A specimen bank will enable scientists to identify
geographic variations in pollutant burdens and to distinguish
22

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may then be tested using whole animals to obtain the more
quantitative data required to confirm and evaluate the risk.
Under contract to the EPA, the Stanford Research
Institute examined twenty pesticides for mutagenicity by
in vitro microbiological assays using the bacterial and yeast
assays. Tests were also conducted for unscheduled DNA
synthesis in human lung fibroblasts with and without meta-
bolic activation and the dominant lethal test in mice (10
compounds only). Under an ancillary contract, the Wisconsin
Alumni Research Foundation performed the sex-linked
recessive lethal test in those compounds which were not
insecticidal.
SEVEN PESTICIDES GIVE MUTAGENIC
RESPONSE
Seven of the 20 pesticides examined gave positive
responses in one or more of the four microbiological
assay procedures. Although a mutagenic response in a
microorganism does not mean that a chemical is a mutagen
in humans, the combination of four separate assay systems
greatly enhances the probability of detecting potentially
hazardous chemicals. Folpet and captan were mutagenic in
all four assay procedures. Chloropyrifos and dinoseb were
positive in the microbial repair-deficient and -proficient
strains. Azinphos-methyl cacodylic acid, and monocrotophos
were positive in the yeast assays and methylparathion was
marginally positive.
The Federal Insecticide, Fungicide, and Rodenticide
Act designates the Environmental Protection Agency as the
governmental body responsible for the safety for all pesti-
cides used in the United States.
In the pesticide review process, EPA emphasizes
development of scientific criteria for evaluating the safety
of compounds substituted for those pesticides found to be
hazardous. In addition to reviewing and evaluating the
literature on pesticides, and maintaining liaison with
industry and academia, laboratory studies are conducted
to obtain additional data. One of these programs is directed
toward gathering mutagenesis data on a selected number
of compounds. Mutagenic agents may cause such genetic
damage as chromosome alterations.
Development of short-term qualitative methods for
evaluating the mutagenic hazard of chemical compounds has
advanced markedly in the last few years. These short-term
tests are a sensitive initial step to screen chemicals quickly
and cheaply for possible toxic effects. Suspect compounds
The combination of assays used in this program is one
means of identifying those pesticides which may present a
mutagenic health hazard. It is apparent that no one assay
system is uniquely capable of detecting the spectrum of
mutagenic effects that different chemical structures may
cause. Those chemicals that show positive responses in
several experimental systems should be evaluated more
thoroughly to establish that they are relatively less toxic
before they are substituted for other pesticides already
considered as a risk to the environment.
¦#
Development of short-term method for
evaluating the mutagenic hazard of
chemical compounds
23

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lives to microwaves at a frequency of either 2450 MHz or
425 MHz, the UHF television transmission frequency. These
irradiations were performed under controlled conditions of
temperature and humidity. At 40 days of age, lymphocytes
were obtained from the blood and lymph nodes of these
rats. The lymphocytes were cultured and their ability to
grow and divide was measured following stimulation with
agents called mitogens. Lymphocyte growth and cell division
in culture following stimulation with mitogens serves as an
indirect measure of their capacity to participate in an
immune response in the body.
CHRONIC EXPOSURE OF RATS TO
MICROWAVE RADIATION MAY
ALTER IMMUNE SYSTEM
Concern about the possible health effects that micro-
wave radiation (microwave ovens, TV and radio transmission,
radar, etc.) can cause in humans has grown in recent years.
In particular, the possible effects of microwaves on the
immune defense system of humans has been of major con-
cern. Investigators, working with animals, have observed
changes in the immune system following microwave exposure,
particularly changes in lymphocytes, a class of white blood
cells that are intimately involved in the body's immune
response system. The findings of these investigators suggest
that the lymphocyte may be a target for microwave radiation
effects. Taking these findings into consideration, the
Experimental Biology Division has initiated studies to deter-
mine if chronic microwave exposure of rats affects lympho-
cyte function.
il
Investigation into the possible effects of
microwaves on immune response system
Results of these experiments have shown that the
chronic exposure of rats, in some cases, leads to changes in
the number of different white blood cell types. Other
findings suggest that lymphocytes from microwave irradiated
rats undergo growth and cell division to a greater extent than
do lymphocytes from nonirradiated control animals. The
means by which these changes occur and the implications
of these changes with respect to the actual immune capacity
of these animals is not known at this time. Furthermore, it
has not been determined whether or not microwaves affect
human lymphocytes in a similar fashion. These results, how-
ever, warrant further investigation into the possible effects of
microwaves on immune response system.
Initially, pregnant laboratory rats were exposed to'
microwaves. The offspring that had been exposed in utero
received additional exposure during the early part of their
24

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INCREASE IN EXENCEPHALY AFTER
MICRON EXPOSURE
Encephalocele in mouse
fetuses. Deleterious structural and mass changes, such as
those seen in these mice, are considered teratologic in
nature.
Because of the rapid increase in the use of microwave-
producing devices by the public (microwave ovens, CB
radios, walkie-talkies, etc.) and by commerce (heating
and curing operations, communication), general population
exposure is increasing. The fetus is expected to be especially
sensitive to deleterious agents. The scientific and public
health interest in the fetotoxic effects of microwaves is
being addressed by the Experimental Biology Division in
its studies of the effects of 2450 MHz microwaves on the
rodent fetus and at power densities which produce little
or no temperature rise.
Teratologic studies, conducted during a two-year
period, demonstrated a small but very significant number
of encephaloceles in mouse fetuses. Exencephaly is an
abnormal condition where the midline of the skull does
not close during development and the brain herniates and
is exposed. Associated with the highest power density
(approximately three times the maximum set forth in
the guidelines for occupational exposure to microwaves)
there was also a decrease in the weight of the near-term
Brain hernia in mice has been associated before with
microwaves at this frequency, but at very much higher inten-
sities. Brain hernia is also associated with stressfully high
body temperatures. Though it appears reasonable that
brain hernia is associated with relatively low levels of
microwaves, it is yet to be ascertained definitely that this
can occur in humans at the very low levels encountered
generally in the environment and at the frequencies observed
environmentally.
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RESEARCH OBJECTIVES
27

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AIR PROGRAMS
28

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investigative program emphasizing the interaction between
population studies and clinical studies involving human
volunteers. In addition, studies using laboratory animals
or biological preparations complement human studies.
HIGHLIGHTS
• The study of human exposure to 1200
O
ng/m (0.6 ppm) 03 for two hours has been
completed and the lung function data analyzed.
Significant symptom reporting and a reduction
of as much as thirty-five percent of ventilatory
reserve capacity occurred in those subjects. One
O
thousand two hundred /ig/m (0.6 ppm) Og
administered over a two-hour period produced
greater decrements in lung function than a
O
smaller dose, 800 nq/m (0.4 ppm) during
four hours.
REGULATED AIR POLLUTANTS
• Analysis of peripheral blood lymphocytes of
subjects exposed to 1200 £(g/m (0.6 ppm)
ozone for one two-hour period revealed
that lymphocyte thymidine incor-
poration in DNA, when stimulated with
phytohemagglutinin, was significantly surpressed
in samples taken at two and four weeks after
ozone exposure. Normal responses occurred
two months post exposure.
RESEARCH OBJECTIVES
Health information was compiled and published in
1969, 1970, and 1971 as part of the criteria upon which to
establish the National Ambient Air Quality Standards
(NAAQS) for nitrogen dioxide (NOj), sulfur dioxide (SO2),
carbon monoxide (CO), total suspended particulates (TSP),
ozone (Og), and hydrocarbons (HC). Research conducted
in the Health Effects Research Laboratory, Research Triangle
Park, North Carolina concerning these pollutants is currently
directed toward expanding and improving this information.
Research is being conducted to obtain additional data to
close research gaps existing at that time and to provide a
scientifically adequate health data base for refining the
existing criteria. The emphasis of this work is upon an
evaluation of exposure averaging times for the NAAQS
and of the adequacy of existing safety margins. The health
benefits of meeting the NAAQS and the health risks of
exceeding the NAAQS on a time-weighted basis are being
investigated. This research is conducted through a com-
prehensive multidisciplinary intramural and extramural
Analysis of peripheral blood lymphocytes
29

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•	Investigators at Stanford University have
completed a study of the effects of 800
O
jig/m (0.4 ppm) ozone for four hours on
human performance and electrophysiological
function. Analysis of the behavioral data
indicates a significant improvement in human
performance during exposure to ozone as
compared to clean air. The electrophysiological
data show no deleterious effect of this level of
ozone on visual evoked potentials during a
sedentary vigilance task.
•	Computer analysis of electrocardiogram ST
segment changes has been accomplished and vali-
dated in CO-exposed dogs resulting in the devel-
opment of a dose/effect function indicating
CO-hypoxemia has about twice the effect of
hypoxic-hypoxemia.
•	CO exposure at altitude has an effect on exercise
performance in altitude-adapted individuals com-
parable to that in subjects studied at sea-level.
•	All projected human behavior tasks involving
exposure to carbon monoxide have been com-
pleted and performance data analyzed. These
EPA studies were factored into a comprehensive
literature review and critique indicating ambient
CO concentrations do not significantly impair
human behavior and task performance. Electro-
physiologic data from the central nervous system
are being analyzed.
• The Infectious Disease Division of the
Department of Pediatrics at the University of
North Carolina has been studying respiratory
infections in a population of children at the
Frank Porter Graham Child Development Center
in Chapel Hill, North Carolina since 1966.
Approximately 375 child years of observation
have been completed. This study is providing
data, not previously available, on the devel-
opment of lung function and pulmonary defense
mechanisms in children and the relationship of
common intercurrent respiratory infections
which are part of a normal life experience. A
preliminary report has been completed and a
portion submitted for publication. The data
suggest that lower respiratory tract involvement
without signs or symptoms of lower airway or
alveolar disease occurs with upper respiratory
infection of varied etiology in childhood.
Acquisition of electrophysiological data
30

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•	Progress continues in refining a mathematical
model to predict interspecies (including human)
differences in respiratory tract distribution and
retention of inhaled gases and aerosols.
•	Research concerning the comparative inhalation
toxicology of Og, NOj, and sulfates continues
to refine their interactions.
•	A program to study the effects of air pollutants
in a tracheal organ culture system has been
initiated.
•	Significant progress continues in the elucidation
of the dose/rate effect of the NO2 standard. A
certain dose administered over shorter periods of
time produces a greater effect than same doses
administered more chronically.
•	Re-evaluation of data from the Pittsburgh Air
Pollution Episode (1975) indicates a possible
10-20% reduction in vital capacity in the most
susceptible 10% of those children from the most
polluted areas.
Study of respiratory tract distribution and
retention of inhaled gases and aerosols
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clinical studies involving human volunteers. In addition,
studies using laboratory animals and in vitro biologic pre-
parations complement human studies.
HIGHLIGHTS
NONREGULATED AIR POLLUTANTS
•	Construction of the CLEANS/CLEVER system
is complete. Environmental operating parameters
for CEL A, one of the clinical environmental
laboratories, have been validated and software
for plethysmography and spirometry are debugged
with these data aquisition systems operational.
The ECG stress operational software has also been
delivered and demonstrated by the contractor.
The protocol for the first study in this facility
is being prepared. Design of the aerosol gener-
ation and control system for CLEANS is com-
plete and construction is scheduled. Most major
hardware items have been ordered.
•	A letter contract with Rockwell Air Monitoring
Center was signed for the operation and main-
tenance of the CLEANS/CLEVER system, and
their key personnel are on site.
RESEARCH OBJECTIVES
Research information is required to explain exposure-
effects relationships between nonregulated (also referred to
as noncriteria) air pollutants and human health. This research
will provide data for determining whether restricting exposure
to particular pollutants is necessary to protect health and, if
so, to what degree exposure should be restricted. Information
presently available concerning sulfates, nitrates, and respirable
suspended particulates suggests that the current standards for
sulfur dioxide and total suspended particulate matter may not
be adequate to protect populations from the potential adverse
health effects of these materials. Therefore, the objective of
studies conducted in this Laboratory concerning these pol-
lutants is to determine the degree of control required to
protect human health. For other nonregulated air pollutants
such as vapor phase organic material (VPOM) as well as some
particulate organic material, we are attempting to answer
the more basic questions. Research on noncriteria pol-
lutants is conducted through a comprehensive multi-
disciplinary intramural and extramural investigative program
emphasizing the interaction between population studies and
Preliminary exposures of human subjects to
100pg/m sulfuric acid mist have begun. The
objective of this study is to relate health effects,
as determined by pulmonary function tests and
cardiac status, to specific concentrations of
sulfuric acid aerosols.
Data on ammonia concentration in exhaled air of
human subjects have been collected for use in
developing a mathematical model to determine
the capacity of ammonia to neutralize inhaled
sulfuric acid.
Dose-response curves for the effect of cadmium,
vanadium, mercury, selenium, arsenic, and zinc
on liver cell viability have been determined.
Toxicity ranking of the metals studied with
respect to cellular viability is Cd > V > SE =
AS > Hg > Zn.
Using fluorescent labeled membrane probes, a
previously undescribed phagocytic capability
of the alveolar macrophage has been observed.
Preliminary data indicate that in vitro effects
of sulfate exposure on alveolar macrophage
function are increased by prior ozone exposure,
indicating possible interaction between these
pollutants.
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Sulfate exposure facility
• Alterations of the electrophoretic profiles of
membrane protein were observed in rabbits
exposed to 0.5 ppm ozone for 72 hours. These
data suggest the possibility that membrane pro-
teins, particularly surface proteins of alveolar
macrophages, may be one of the biochemical
targets of air oxidants. Alteration or damage to
the membrane protein may contribute to the
retarded phagocytic activity of alveolar macro-
phages and, consequently, may impair the
defense mechanisms of the respiratory tract.
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REGULATED AND NONREGULATED
POLLUTANTS ASSOCIATED WITH
TRANSPORTATION
acid emissions were very low, averaging 2.7
mg/mile, carbon monoxide emissions were
in excess of national emissions standards for
the majority of vehicles tested.
•	Using an infectivity model, investigators have
found that manganese oxide produces a toxic
effect at concentration levels lower than the
threshold limit value for manganese.
•	To date, studies using experimental animals
involving platinum sulfate show no significant
effects on leucocyte metabolism or on allergic
response although it did show delayed hyper-
sensitivity when compared with albumin. It has
been shown to be a severe eye irritant.
•	Studies concerning behavioral effects of exposure
to platinum, by ingestion, show that platinum
has marginal effects on general activity and
exploratory behavior in the adult mouse. On
day 12 of gestation, platinum altered postnatal,
neonate, and adult offspring behavior. Pups
exposed in utero exhibited depressed weight,
rate of weight gain, and activity.
RESEARCH OBJECTIVES
A Multidisciplinary research program focusing on
public health consequences of nonregulated pollutants
from mobile sources began in 1974. The program is designed
to provide a scientific basis for regulatory decision-making
regarding the future status of mobile source emission con-
trol. Primary emphasis is on the evaluation of nonregulated
emissions from advanced automotive control systems (prin-
cipally catalysts). This objective will be accomplished
through comprehensive clinical, toxicological, and biological
studies. Since this program involves several other Labora-
tories in ORD, HERL-RTP provides program coordination
and prepares comprehensive reports for the Administrator,
Congress, and the Assistant Administrator for Research and
Development.
Preliminary experiments indicate that sulfuric
acid has an adverse effect on beans, hybrid
poplar, corn, and soybeans. Symptoms, marginal
and tip necrosis, have been similar in all
species studied. This type of symptom has not
been reported previously for acid injury.
A study designed to determine the effects of
sulfuric acid and sequential combinations of
sulfuric acid and ozone was completed. Results
reveal that when ozone exposure precedes the
sulfuric acid, there is a statistically significant
enhancement in mortality over controls. The
exposure does not produce any statistically
significant effects.
HIGHLIGHTS
• Data through March 1976 on in-use catalyst-
equipped vehicles shows that though sulfuric
34

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A second rough draft of the revised Oxidant-
Hydrocarbon Criteria Document was completed
and circulated for review.
•	The first rough draft of the revised Nitrogen
Oxides Document was completed.
•	The Nitrosamine STAR Document was issued as
a pre-publication edition and final printing is
in progress.
•	The Vanadium STAR Document was completed
and submitted to the Government Printing
Office for publication.
CRITERIA DOCUMENTS
RESEARCH OBJECTIVES
The Health Effects Research Laboratory, Research
Triangle Park, North Carolina provides documentation
which critically reviews, evaluates, and interprets per-
tinent scientific and technical literature concerning environ-
mental pollutants. The latest available data on the sources,
prevalence, and manifestations of recognized air pollutants
are compiled, thus providing the basis for National Ambient
Air Quality Standards (NAAQS). This involves the issuance
and revision of Air Quality Criteria Documents, the pre-
paration of Scientific and Technical Assessment Reports
(STAR), and the identification of areas where additional
research is required to produce adequate criteria for issuing
or revising standards.
HIGHLIGHTS
• A draft Lead Criteria Document was prepared
and distributed for comment. A second draft
has also been completed and distributed for
critical review.
Criteria document preparation
• Assistance was provided in preparation of review
documents on pesticides toxicology for the
FAO/WHO Joint Meeting on pesticide residues.
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EFFECTS OF PESTICIDES
AND TOXIC SUBSTANCES
36

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HIGHLIGHTS
•	The compounds captan and folpet were not
teratogenic by the inhalation exposure route.
Effects of exposure by oral and subcutaneous
routes are still under study.
•	Kepone was not found to be teratogenic nor did
it impair the reproductive capabilities of male
neonate rats.
•	The effects of polychlorinated biphenyl isomers
on liver enzymes relate well to their in vivo
toxicity. In general, the effects increase with
increasing degree of chlorination.
•	The interval histogram of smooth muscle from
the rat gut has been shown to be an adequate
parameter for in vivo measurements. Baygon
and carbaryl produced an effect in the interval
PESTICIDES	histogram at a dosage level which did not
produce overt symptoms.
RESEARCH OBJECTIVES
The primary emphasis in pesticides research being
conducted at the Health Effects Research Laboratory is in
the collection of data required by the Office of Pesticide
Programs (OPP) in the general areas of registration, label
review, hazard classification, and tolerance setting. OPP has
placed particular significance on the re-registration process,
and RPAR (Rebuttable Presumption Against Registration)
Program. The majority of the health effects data required
by OPP is supplied by the registrants; however, supple-
mentary data and missing information are supplied by the
Office of Research and Development (ORD). The current :
program is being conducted through a multidisciplinary
approach involving the investigation of the effects of
commonly used pesticides in laboratory animals, exam-
ination of the potential human hazard of "new generation"
pest control agents, the analysis of pesticides and their
transformation products in human and environmental
samples, and the evaluation of human population exposure.
Investigation of the effects of commonly used
pesticides in laboratory animals
37

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•	In long-term, low-level studies with the com-
pound leptophos in chickens, hens developed
paralysis at dosages as low as 10 mg/kg and
showed ataxia at 1 mg/kg. All control and
parathion-dosed hens were normal.
•	A single oral dose of 100 mg/kg of EPN caused
neurotoxicity, characterized by ataxia, in
atropinized chickens.
•	The fungicides, maneb and zineb, on apple and
peach foliage, sprayed with parathion, did not
increase conversion of parathion to its more
toxic metabolites.
•	DDUP bioassays (3,000slides) were reviewed
for OPP's re-registration program.
•	determinations were completed on three
pesticides—MSMA, dinoseb, and decamethrine—
by different routes of exposure.
•	A study in which male rats were fed 0.1%
pentachlorobenzene in the diet for 67 days
revealed no effects on fertility, fecundity,
or offspring survival.
•	Exposure of female rats to dietary pentachloro-
phenol (20 and 100 ppm) for eight months
resulted in reduced serum cholesterol and
cholesterol ester levels. This effect was not
noted at the 500 ppm dose in females nor in
any level studied in males.
•	Preliminary neurophysiological studies with an
EBDC fungicide (maneb) and a major metabolite
(EBIS) revealed reversible neuropathies in
rodents.
•	Excellent resolution has been obtained for
complex pesticide mixtures using an interfaced
gas chromatography column system and high
resolution mass spectrometry.
•	Application of motor activity techniques to
subacutely exposed neonates was successfully
employed in a study of the relative effects of
Mirex and Kepone in rats. Mirex produced no
change in spontaneous activity although detect-
able levels of the pesticide were present in the
brain. Kepone produced hyperactivity which
correlated with high brain levels.
38
Slides are reviewed for OPP's re-registration program

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PESTICIDES (SUBSTITUTE CHEMICALS
PROGRAM)
Animal being dosed in pesticides study
RESEARCH OBJECTIVE
Public Law 93-135 (1973) delegated responsibility to
EPA for reviewing of the scientific and economic implications
of utilizing substitute chemicals that have replaced certain
cancelled substances. This process entails identification of
the hazards associated with the use of each compound, and
subsequent proposal of acceptable alternate substances for
those compounds deemed hazardous to human health.
Research being conducted at the Health Effects Research
Laboratory, Research Triangle Park, North Carolina empha-
sizes a thorough review of scientific literature in addition
to the execution of toxicity studies aimed at filling gaps
in the health effects data base. This research involves both
examination of human exposure to various compounds and
analysis of controlled laboratory animal studies.
HIGHLIGHTS
• Preliminary investigations on the derivation
of three carbamate pesticides (Barbon,
Carbofuran, and Chlorprophen) have been
completed. This process permits GLC deter-
mination of these compounds under conditions
which produce decomposition of the undersensi-
tized carbamate.
•	Lethal doses of chlordimeform, a formam-
idine pesticide, led ultimately to cardiovascular
depression. These effects were attributed to
local anesthetic action, and may account for
the lethal result of these pesticides.
•	Two active migrant crews harvesting pesticide-
treated vegetable crops were studied. Signifi-
cant depression of the plasma cholinesterase
level was found in association with exposure,
especially in cool temperature zones.
•	The Ames assay has been carried out on a group
of compounds of interest in the SCP Program,
including DDT, DDE, dieldrin, heptachlor, hepta-
chlor epoxide, diazinon, carbaryl, nitrosocarbaryl,
39

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linuron, and captan. The results revealed two
active compounds: captan and nitrosocarbaryl.
In further tests, the metabolism of carbaryl
within the Ames assay system was shown to
be representative of in vivo metabolism of
the compound.
•	The compound dieldrin was identified and
quantified at the 0.01 ppm level in chicken
fat using the Hall electrolytical conductivity
detector system.
•	Initial evaluation of polyurethane foam in the
SURC air sampler for pesticides and environ-
mental pollutants was completed. Using this
collection technique, monitoring for PCB
emissions from landfills began.
•	Subacute dietary studies with ETU, a car-
cinogenic metabolite of several widely used
fungicides, were completed. A no-effect level
of 25 ppm was found based upon biochemical
and pathological evaluation in target organs.
•	A subchronic rat feeding study (90 days) with
DNBP (Dinoseb) was completed together with a
single generation reproduction study. Preliminary
results suggest definitive effects at levels of 200
ppm in reproduction and on 8 of 14 clinical
chemistry parameters.
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TOTAL QUALITY ASSURANCE PROGRAM FOR
PESTICIDE RESIDUE MEASUREMENTS
•	Investigation of the stability of pesticides
in solvent solutions continued.
•	The Hall detector is being evaluated to
ascertain its stability for determining pesticide
residues in extracts of fatty material.
•	Reference standards of blood and fat were
furnished to laboratories. A report was issued
on results of all data submitted by participating
laboratories. Analytical data were processed
on serum check sample #46 which was dis-
tributed as a blend sample to 18 epidemiological
studies and related laboratories. Data from these
labs continue to indicate high quality work.
•	In response to 659 requests from pesticide
research laboratories for reference standards,
5,479 analytical standards were mailed.
•	Maintenance procedures on electronic instru-
ments, such as gas chromatographs in the par-
ticipating laboratories, were conducted in order
to assure accurate results. This work involved
repair and/or calibration of 358 electronic
instrument modules.
RESEARCH OBJECTIVES
The reliability of all EPA pesticide analysis labora-
tories may be evaluated on the strength of the Quality
Assurance Program. To insure accurate pesticide analyses,
a thorough analytical quality control program is conducted.
This comprehensive program involving EPA, contract, and
other laboratories includes methods development and stan-
dardization, provision of high purity analytical standards,
instrument modification, and repair services. This quality
assurance support in pesticide residue analysis is provided
to the Office of Pesticide Programs (OPP): (a) Epidemiologic
Studies Laboratories; (b) National Human Monitoring
Program; and (c) other related OPP programs.
HIGHLIGHTS
• In determining the validity of analytical methods
for pesticide monitoring, two commercially
available gas chromatograph integration systems
were evaluated.
\
Method standardization
41

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TOXIC SUBSTANCES
Toxic substance screening
mine exposure levels to various toxic chemicals.
Investigations will determine if a relationship
exists between the levels in blood, saliva, and
urine, and if the levels in saliva are indicative
of exposure.
• Using screening tests, fourteen technical grade
pesticides gave negative results in two different
bacterial DNA repair systems. Three of the com-
pounds (acephate, demeton, and trichlorphon)
had previously shown positive results in the point
RESEARCH OBJECTIVES	mutational assay system (bacterial and yeast).
Several hundred new chemicals are introduced
into commercial use each year, even though in many cases
their potential health effects are unknown. Therefore,
research is being conducted to determine the potential
hazards to human health from exposure to these pollutants,
to develop methods by which various classes of toxic sub-
stances can be rapidly screened for specific biological
activity, and to develop methods by which persistence,
disposition, and biological activity can be predicted.
HIGHLIGHTS
• A new mutagenic assay system involving
activation by plant enzyme systems is under
development and shows promise.
•	A multigeneration study of the compound
hexachlorobenzene (HCB) has shown that
HCB in diet concentrations as low as 20
ppm has adverse effects on reproduction.
•	Research is underway to determine the potential
value of saliva as an additional medium to deter-
42

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developed in vivo microlesion test and mammalian cell
culture systems not only for mutagenicity but also for a
potential of detecting neoplastic transformation. Such
prescreened pesticides include captan, folpet, and bromacil.
Herbicides that have been shown to be activated in plants by
metabolic conversion into mutagens are other candidate
compounds. A recommended model compound is atrazine.
Examining these compounds will assist in the validation,
evaluation, and standardization of the heritable microlesion
test which is designed to increase the number of loci which
can be assayed for the induction of transmissible mutations
and for predicting potential harm to future generations of
mammalian populations.
HIGHLIGHTS
NATIONAL CENTER FOR TOXICOLOGICAL
RESEARCH
RESEARCH OBJECTIVES
NCTR, through mutual DHEW and EPA agreement,
provides a collaborative toxicological research program in
carcinogenesis, mutagenesis, teratogenesis, comparative meta-
bolism, and improved toxicological testing methodology
addressing EPA priority needs in those research areas. These
studies are being designed to evaluate toxicological effects
following long-term, low-level exposures.
Emphasis is placed on compounds or models to
be studied by mutual agreement, especially those compounds
(rotenoids and dithiocarbamates) suspected of producing
neoplasms through a direct or indirect hormonal effect.
Other etiologic mechanisms, immune responses or immunity,
and new biologic agents for pest control (viruses), are sug-
gested for study as oncogens.
For mutagenesis studies, those pesticides that have
been shown to be either weakly or strongly mutagenic in
prescreening tests (Drosophilia systems and microbial
screens) are recommended models for study in the newly
•	Literature reviews are being conducted on
several compounds including rotenoids and
dithiocarbamates. Also, due to the possible
effects of these chemicals on cellular develop-
ment, literature reviews of other routes of
exposure such as transplacental carcinogenesis
studies are being made.
•	Specific protocols outlining experiments to
determine carcinogenicity of rotenone are being
developed. A meeting was held with members
of NCTR and EPA staff to discuss development
of the chronic dose-response studies with rote-
none. The NCTR Analytical Chemistry Branch
has begun preliminary work on developing the
most satisfactory analytical method for con-
firmation of chemical levels in dosed feed.
•	NCTR has developed the capacity to detect
genetic alterations at approximately 200-400
loci in the C57BL/6J strain of mice. This number
of loci is monitored by enzyme activity analysis
of approximately 30 enzymes from different
tissues and electrophoretic analysis of approx-
imately 27 enzymes from different tissues.
•	NCTR has also developed the capacity to
detect specific gene mutations in the Chinese
Hamster Ovary/Hypoxanthine Phosphoriboxyl
Transferase somatic cell system and are prepared
to validate this prescreen system using a variety
of representative chemicals, including pesticides.
•	A selected group of approximately 10 experts
in the area of inhalation toxicology have been
identified and have agreed to participate in the
feasibility study. The first meeting of the study
group was held at NCTR.
43

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HEALTH EFFECTS OF EXPOSURE
TO RADIANT ENERGY
44

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HIGHLIGHTS
• Replication of the initial observations that
chronic pre and postnatal exposure of rats to a
UHF-TV frequency at a power density of 10
mW/cm results in increased PHA-stimulated
mitotic activity of lymphocytes was successful.
Because of the high normal variability in these
responses, a third run is in progress in order
to be assured that the results are not artifactual.
• Initial testing of the thermographic camera/
minicomputer/software complex to determine
the microwave energy deposition patterns in
biological systems was successful. This will
permit identification of "hot spots" of localized
high energy deposition in experimental animal
systems and the continuation of research on
potentially critical structures.
RADIANT ENERGY	• Analysis of the data from the study of tera-
tologic effects of intrauterine exposure of mice
o
to various power densities (3,4-28 mW/cm ) of
2450 MHz radiation was completed. The results
show a statistically significant increase in
encephaloceles in irradiated animals as a group
compared to nonirradiated and in the mean live
fetal weight of the animals exposed to 28
mW/cm during gestation.
Teratological study
RESEARCH OBJECTIVES
Research is being conducted to determine the need
for establishing an environmental standard for nonionizing
radiation. Therefore, HERL scientists are investigating the
biological effects of exposure to microwave and radio fre-
quencies to which human populations are frequently
exposed. Chronic and acute exposures to 100 MHz (FM-radio
frequency), 425 MHz (UHF-TV frequency), 2450 MHz
(microwave oven frequency), and 9000 MHz (search radar
frequency) are being studied for their effects on neuro-
biology, developmental, biochemical, immunologic, and
genetic systems. Reflex development, spontaneous activity,
and social behavior are being measured in chronically
exposed rats. Changes in learning and memory are being
studied in primates and rodents. Effects of prenatal and
postnatal exposure of rodents to nonionizing radiation are
also being evaluated. In addition, mechanisms of inter-
action of electromagnetic radiation (EMR) with biological
systems and the influences of amplitude-modulation (AM)
carrier waves at frequencies identified as natural biological
rhythms are being investigated.
45

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HEAVY METALS
46

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NONPESTICIDE ORGANIC AND INORGANIC
SUBSTANCES REACHING MAN
THROUGH MULTIPLE ROUTES
In addition, whole-body retention, organ distribution, and
in vitro investigations complement these dose-effects studies.
Another objective of this program is the development
of protocols and analytical procedures for the National
Environmental Specimen Bank.
HIGHLIGHTS
•	The National Bureau of Standards (NBS)
Analytical Chemistry Division has developed and
reported on various analytical techniques to be
utilized to detect trace quantities of elemental
and organic substances in a variety of matrices.
This information is to be included in the oper-
ation of the National Environmental Specimen
Bank 
-------
•	The Cooperative International Study on
cadmium in biological tissues was designed
to establish normal human tissue levels and
body burdens of cadmium, zinc, and mercury as
a function of age. The results show cadmium
levels in Japanese tissues > American > Swedish.
Cadmium and lead burdens generally increase
with age whereas zinc and mercury do not.
Cigarette smokers have greater levels of cadmium
and lead in all tissues than do nonsmokers.
•	The Cleveland study of lead in deciduous teeth
and its relationship to children's learning, emo-
tionality, and physical characteristics reports a
positive correlation of lead in teeth with the
number of lead-using industries in the vicinity
of the children's schools. Elevated tooth-lead
levels did not correlate with auto traffic or
airborne lead levels. In a separate study, air-
borne lead levels did correlate with teacher
evaluations of the children's learning and
emotional development.
Pilot studies to determine the distribution of
manganese in rats during prolonged exposure
have been completed and the results analyzed
November 1976.
In defining the developmental and behavioral ef-
fects of lead exposure in the mouse, two signifi
cant results have been recorded- delayed sexual
maturation and reduced locomotor activity.
48
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POLLUTANTS ASSOCIATED WITH
ENERGY DEVELOPMENT
49
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lead were tested and found to decrease the adino-
sine triphosphate (ATP) content of the exposed
cells. Results suggest that ATP content may be
a sensitive indicator of particle toxicity and
altered cell function.
• A sulfuric acid aerosol generator has been
developed to assist in studying the influence of
one of the respirable effluents that may result
from increased coal combustion.
A new system for assessing potential carcino-
genesis by bacterial mutagenesis is being applied
using material from alternate energy sources to
detect carcinogens and their metabolites in rat
urine. Preliminary studies of human urine are
also being conducted.
Assessment of potential carcinogenesis
HEALTH EFFECTS FROM POLLUTANTS
ASSOCIATED WITH ENERGY DEVELOPMENT
RESEARCH OBJECTIVES
Current research emphasis at HERL is focused on
the collection of health effects data as a result of exposure
to sulfates, particulates, and organics. Specific objectives
include the identification of hazardous agents associated
with nonnuclear energy technologies, development of more
rapid and sensitive methods to evaluate dose to man, deter-
mination of the metabolism and fate of hazardous agents
associated with alternate energy technologies, and eval-
uation of the hazards of exposure of normal, susceptible,
and stressed population groups.
HIGHLIGHTS
• Pilot studies, using rabbits, have confirmed
the feasibility of studying the relationship
between carcinogen metabolism in the alveolar
macrophage and the induction of lung cancer.
Fly ash particles deliberately coated with
oxides of cadmium, manganese, nickel, and
50
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• Comparative toxicity levels of a series of metallic
sulfates and chlorides has been completed. The
results show (1) no significant difference in
toxicity between sulfate and chloride salts of
Zinc (Zn), Manganese (Mn), Nickel (Ni), Copper
(Cu), or Mercury (Hg); (2) Zinc Ammonium
Sulfate [ZnlNH^JjSO^-eh^O] was found to
be more toxic than zinc sulfate (ZnSO^); (3)
Mercury (Hg), Cadmium (Cd), and Vanadium
(V) were found to have significant interactions
with other trace elements. For instance,
Selenium 
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ENVIRONMENTAL ASSESSMENT INTERFACE
AND RESEARCH STUDIES
meeting at which IERL—RTP projects were
reviewed in detail and appropriate recommen-
dations regarding health related subjects were
provided by the HERL—RTP staff.
• Recommended protocols for in vitro bioassays
were drafted by HERL—RTP staff and were
reviewed by NIEHS scientists. In vitro and
in vivo protocols for health and ecological
effects assessment were combined for maximal
effectiveness within IERL cost constraints and
presented before the Steering Committee on
October 19, 1976. Based upon these recom-
mendations, Battelle—Columbus Laboratories
prepared a report on Level I Environmental
Assessment—Biological Tests. A draft report
was available on January 1, 1977. Extramural
review of this document was formally recom-
mended by the bioassay subcommittee, and
appropriate reviewers were recommended.
Following extensive extramural review, protocols
for in vitro health related research were revised
by HERL—RTP staff and provided to Battelle—
Columbus Labs for inclusion in their report to
IERL.
RESEARCH OBJECTIVES
The purpose of this program is to provide the Industrial
Environmental Research Laboratory—RTP, Office of Energy,
Minerals, and Industry, Environmental Assessment Program;
with the necessary input regarding the potential health
effects of individual effluents and effluents arising from the
development and utilization of alternate sources of energy.
•	HERL—RTP staff has participated in conferences
and contract negotiations between IERL—RTP
and contractors including Westinghouse,
Battelle—Columbus, Monsanto, and Research
Triangle Institute.
•	HERL-RTP staff has critically reviewed several
documents pertinent to in vitro bioassay
including the Battelle Report mentioned above.
•	HERL-RTP staff has arranged for testing of
a number of IERL—RTP samples for muta-
genic and cytotoxic activity.
HIGHLIGHTS
• Preliminary meetings of the Subcommittee on
Bioassay Procedures were held October 7, 1976,
at HERL-RTP and on October 18,1976, at
HERL-Cincinnati, to finalize and prioritize
recommended bioassay procedures for environ-
mental assessment. On October 19, 1976, these
procedures were presented in detail before the
Environmental Assessment Steering Committee
in Cincinnati. In February 1977, the OHEE—
OEMI Steering Committee held a 2-1/2 day
52
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CARCINOGENS
53
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Louisiana study is in progress. After consulta-
tion among members of HERL— RTP staff
and individuals at the Montana State Department
of Health, it was decided that Montana would
initiate that study with technical assistance,
consultation, data processing support, statis-
tical analyses, and aerometric measurements
provided by HERL—RTP.
CONTRIBUTION OF ENVIRONMENTAL
CARCINOGENS TO CANCER INCIDENCE IN
THE GENERAL POPULATION
RESEARCH OBJECTIVES
Through an Interagency Agreement with
Brookhaven National Laboratories (ERDA),
the National Institute of Environmental
Health Sciences (NIEHS) has supported the
development of a mutagenesis test system
(tradescantia) which appears to be especially
sensitive to exposure to mutagens in the air.
Following experiments under controlled
exposure conditions in chambers, a mobile
laboratory was constructed to allow testing in
actual, as opposed to simulated, exposure
situations. This mobile laboratory has potential
for identifying areas with probable exposure to
carcinogens and the Population Studies Division
is cooperating with NIEHS and BNL in the initial
round of experiments in ten selected geographic
locations. In addition to the provision of aero-
metric and other technical support for the field
tests, both vapor phase and particulate-pollutants
are being collected for further mutagenesis and
carcinogenesis testing and for chemical analysis.
Tests were conducted in Charleston, West Virginia
in March and in Birmingham, Alabama in April.
The purpose of these studies is to identify candidate
compounds or categories of compounds for carcinogenicity
assessment in mammalian and in vitro test systems. Using
available vital statistics, populations with increased cancer
incidence will be identified and further studied to delineate
specific neoplasm type and relevant demographic factors.
These cancer incidence data will then be related to known
or suspected chemical carcinogens, determined by environ-
mental monitoring and emissions inventories, which are most
likely due to the specific industrial composition of the study
area. These environmental factors and health parameters will
be correlated to accomplish the objectives of this program.
HIGHLIGHTS
• Two sites have been selected for possible inten-
sive study—one is in Montana and the other,
Louisiana. Both show exceptionally high rates
of lung cancer in both sexes. Planning for the
Tradescantia, a plant mutagenesis test system
54
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BIBLIOGRAPHY
55
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56
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December 1976.
Rhodes, J. W., D. E. Johnson, and R. G. Lewis. Evaluation of Collection Media for Measurement of Pesticides
and Polychlorinated Biphenyls in Ambient Air. Presented at the 173rd ACS Meeting, New Orleans, La.,
March 1977, Paper No. PEST 77.
Schaper, R. A., and L. A. Crowder. Uptake of 36CI-Toxaphene in Mosquitofish, Gambustia affinis. Bull. Environ.
Contam. Tox., 15(51:581-587, May 1976.
Shafik, Tal M., and A. Peoples. Chemical Methodologies for Determination of Man's Exposure to Biodegradable
Pesticides. Presented at Conference on Alkyl Phosphate and Cholinesterase Determinations as Related to
Farm Worker Protection and Re-Entry, held March 1977 at Office of Pesticides Programs, Technical Services
Division, Washington, D. C.
Smith, L. W., and J. F. Borzellica. Uptake of Cadmium in Rat Submaxillary Slices. ASPET, 1976.
Smith, L. W., and J. F. Borzellica. The Excretion of Cadmium and Mercury in Saliva. Submitted for presentation
SOT, 1977.
Sovocool, G. W., R. G. Lewis, R. L. Harless, N. K. Wilson, and R. D. Zehr. Analysis of Complex Pesticide Mixtures
by Gas Chromatography-Mass Spectrometry: Composition of Technical Chlordane. Submitted to Anal. Chem.,
November 1976.
Sovocool, G. W., R. L. Harless, N. K. Wilson, and R. D. Zehr. A Study of the Formation of the Base Peak Fragment
in the Mass Spectrum of a Tricyclic Chlorinated Hydrocarbon of the C10 Series. Submitted for presentation
at the 25th Annual Conference of Mass Spectrometry and Allied Topics, Washington, D.C., May 20 to June 3,
1977.
Stevens, J. T., J. D. Farmer, and L. L. Hall. Species Comparison of the Binding of the Organic Arsenical Herbicide,
Cacodylic Acid to Erythrocytes. Abstract for Society of Toxicology Meeting.
Stevens, J. T., L. L. Hall, J. D. Farmer, L. C. DiPasquale, N. Chernoff, and W. F. Durham. The Disposition of 14C-and/or
74 As-cacodylic Acid in Rats After Intravenous, Intratracheal and Peroral Administration. Environ. Health Perspect.
Accepted for publication.
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Stevens, J. T., L. L. Hall, J. D. Farmer, L. C. DiPasquale, and W. F. Durham. The Disposition of 14C-and/or
74 As-cacodylic Acid in Rats After Intravenous, Intratracheal and Peroral Administration. International
Conference on Environmental Arsenic. October 1976.
Stevens, J. T., J. D. Farmer, and L. L. Hall. 1977. Species Comparison of Binding of Cacodylic Acid to Erythrocytes.
Presented at 16th Annual Society of Toxicology, Toronto, Canada, March 1977.
Wilson, N. K., and G. W. Sovocool. Spectroscopic Characterization of Some Chlorinated Tricyclic Hydrocarbons of
the C1Q Series: Chlordanes, Chlordenes and Nonachlors. Accepted for publication in Org. Magn. Reson.
Wolfe, H. R. Field Exposure to Airborne Pesticides. In: Air Pollution from Pesticides and Agriculture Processes. Robert
E. Lee, Jr., ed., pp. 137-161, CRC Press Cleveland, 1976.
RADIANT ENERGY
Allis, J. W., C. F. Blackman, M. Fromme, J. Black, and S. Benane. Use of Heating and Cooling Curves to Measure
Microwave Energy Absorption in Biological Samples. Presented at International Union of Radio Sciences
Symposium on Biological Effects of Electromagnetic Waves. Amherst, Mass. October 1976.
Berman, E. Teratologic Effects on Mice'of Exposure to 2450 MHz Radiation. Presented to Office of Telecommun-
ications Policy, February 1977.
Elder, J. Effects of Microwave Radiation on Immune Defense Systems. Presented to Office of Telecommunications
Policy, February 1977.
Gage, M. I. Effects of Single Exposures to 2450 MHz Microwave Irradiation on Rat Behavior. Presented at URSI
Symposium on Biological Effects of Electromagnetic Waves, Amherst, Mass. October 1976.
Huang, A. T., J. A. Elder. Lymphycyte Transformation Induced by Microwave Radiation. Presented at URSI
Symposium on Biological Effects of Electromagnetic Waves, Amherst, Mass., October 1976.
Kinn, J. B. Whole Animal Absorption. Effects of Weight and Exposure Geometry. Presented at URSI Symposium
on Biological Effects of Electromagnetic Waves, Amherst, Mass., October 1976.
Rochalska, M., and Z. Szot. Incorporation of Organically Bound Tritium in Food into Some Organs of the Rat.
Submitted to Int. J. Radiat. Biol.
Smialowicz, R. J., and C. G. Liddle. Effects of Chronic Exposure to 2450 MHz on Circulating Lymphocytes in
Rats Exposed Through Gestation and Postnatal Life. Presented to Electromagnetic Radiation Advisory
Council to the White House Office of Telecommunications Policy, Washington, D. C.
Ziemba-Zak, B., E. Bocian, I. Radwan, 0. Rosuk, and J. Sablinski. Radiation Induced Chromosome Aberrations in
the Rat Peripheral Blood. Submitted to Mutation Res.
HEAVY METALS
Becker, D. A., and E. J. Maienthal. Evaluation of the National Environmental Specimen Bank Survey. NBS Report
for EPA clearance.
Gray, L. E., and L. W. Reiter. Delayed Development in Lead Exposed Mice. In: The Effects of Lead Exposure
on CNS Function-A Workshop on the Animals Models. U. S. Environmental Protection Agency,
Hendersonville, N. C., October 1976. To be published in Environmental Health Sciences.
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Goldstein, G. M. The National Environmental Specimen Bank—Its Concepts, History, and Objectives. Presented at
the Biological Specimen Collection International Workshops, Luxembourg, April 1977.
Reiter, L. W., and M. E. Ash. Neurotoxicity During Lead Exposure in the Rat. Toxicol. Appl. Pharmacol., 37:160,
1976.
Reiter, L. W., Effects of Early Postnatal Exposure to Neurotoxins. J. Occup. Med., in press.
Reiter, L.W., G. E. Anderson, M. E. Ash, and L. E. Gray. Locomotor Activity Measurements in Behavioral Toxi-
cology: Effects of Lead Administration on Residential Maze Behavior. In: Behavioral Toxicology: An
Emerging Discipline, H. Zenick and L. W. Reiter, eds., 1977.
Reiter, L. W., K. Kidd, G. Ledbetter, and N. Chernoff. Comparative Behavioral Toxicology of Mirex and Kepone in
in Rat. Presented at the Annual Meeting of Society for Toxicology, Toronto, March 1977.
POLLUTANTS ASSOCIATED WITH ENERGY DEVELOPMENT
Huisingh, J. L., J. A. Campbell, and M. D. Waters. Evaluation of Trace Elements Interactions Using Cultured Alveolar
Macrophages. Presented at 16th Annual Hanford Biology Symposium on Pulmonary Macrophages and
Epithelial Cells, September 1976.
The Status of Indoor Air Pollution Research, 1976. Final Report for Phase I of Indoor Air Pollution Studies.
HERL—RTP Pilot Studies Procedure Manual: Level 1 Environmental Assessment Biological Tests. Draft Final Report
prepared for Industrial Environmental Research Laboratory, Office of Energy, Minerals and Industry, Research
Triangle Park, N. C. 2771 1 by Battelle Columbus Laboratories, Columbus, Ohio.
Toxic Effects of Cadmium Chloride Using a Tracheal Ring System, Environ. Research, 13:111-120, 1977.
Synergistic Effects of Sulfuric Acid Aerosols and Ozone on Lung and Air Way Metabolism. Abstract and Presentation,
Catalyst Research Program, Sulfuric Acid Research Review Committee, Hendersonville, N. C., 1977.
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