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NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES



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FY 1983 ANNUAL REPORT
October 1, 1982 through September 30, 1983



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CONTENTS

Page



OFFICE OF THE DIRECTOR
Summary Statement



PROGRAMS OF THE OFFICE OF THE DIRECTOR
GENETICS

Office of the Associate Director for Genetics, Summary

Statement 7

HEALTH HAZARD ASSESSMENT

Office of Health Hazard Assessment, Summary Statement ... 13

Individual Project Reports 15

Research Contract Narratives 36

INTERNATIONAL PROGRAMS

Office of the Assistant to the Director for International

Affairs, Summary Statement 41

PROGRAM PLANNING AND EVALUATION

Office of Program Planning and Evaluation, Summary

Statement 47

FACILITIES ENGINEERING

Office of Facilities Engineering, Summary Statement .... 55
HEALTH AND SAFETY OFFICE

Health and Safety Office, Summary Statement 61

LIBRARY

Library and Information Services Office, Summary
Statement 67

INTRAMURAL RESEARCH PROGRAM

OFFICE OF THE SCIENTIFIC DIRECTOR 71

LABORATORY OF BEHAVIORAL AND NEUROLOGICAL TOXICOLOGY

Summary Statement 75

Individual Project Reports 84

Research Contract Narratives 141

LABORATORY OF GENETICS

Summary Statement 147

Individual Project Reports • • • 153

LABORATORY OF MOLECULAR BIOPHYSICS

Summary Statement 257

Individual Project Reports 261

Research Contract Narratives 331

LABORATORY OF PHARMACOLOGY

Summary Statement 337

Individual Project Reports 345

LABORATORY OF PULMONARY FUNCTION AND TOXICOLOGY

Summary Statement 399

Individual Project Reports 404

Research Contract Narratives 446

LABORATORY OF REPRODUCTIVE AND DEVELOPMENTAL TOXICOLOGY

Summary Statement 453

Individual Project Reports 472



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Page

COMPARATIVE MEDICINE BRANCH

Summary Statement 513

Individual Project Reports 515



TOXICOLOGY RESEARCH AND TESLING PROGRAM

Office of the Director for Toxicology Research and Testing Program

Summary Statement 531

Research Contract Narratives 534

CARCINOGENESIS AND TOXICOLOGY EVALUATION BRANCH

Summary Statement 551

Individual Project Reports , 555

Research Contract Narratives 580

CELLULAR AND GENETIC TOXICOLOGY BRANCH

Summary Statement 591

Individual Project Reports 594

Research Contract Narratives 638

CHEMICAL PATHOLOGY BRANCH

Summary Statement 689

Individual Project Reports. ... ........ 702

Research Contract Narratives. .... 710

PROGRAM OPERATIONS BRANCH

Summary Statement 723

Research Contract Narratives. ... 733

PROGRAM RESOURCES BRANCH

Summary Statement .... 785

Research Contract Narratives 787

SYSTEMIC TOXICOLOGY BRANCH

Summary Statement 799

Individual Project Reports . 801

Research Contract Narratives. ... . 848

BIOMETRY AND RISK ASSESSMENT PROGRAM

Office of the Director for Biometry and Risk Assessment Program

Summary Statement 871

COMPUTER TECHNOLOGY BRANCH

Summary Statement 875

Research Contract Narratives .... .... 876

EPIDEMIOLOGY BRANCH

Summary Statement 879

Individual Project Reports ...... 880

STATISTICS AND BIOMATHEMATICS BRANCH

Summary Statement .... ........ 901

Individual Project Reports ................ 903

Research. Contract Narratives 918



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Page

EXTRAMURAL PROGRAM

Office of the Associate Director for Extramural Program

Summary Statement 923

Research Highlights: Environmental Health Sciences (EHS)
Centers Program 925

Research Highlights: Regular Research Grants Program 956



INDEXES

Extramural Research Highlights 997

Individual Project Reports . . , 985

Research Contract Narratives 999



OFFICE OF THE DIRECTOR



OFFICE OF THE DIRECTOR
Summary Statement



In April of this year, the first scientists from the Intramural Research Program
occupied laboratory space in the Institute's new building. Since that time
there has been a continuous flow of scientific and support staff into the
laboratory modules. Occupancy of the new laboratories was completed by the end
of August and the leasing of the Northrop Laboratory has been terminated.

Even with the temporary disruption of laboratories preparing to move and moving
there has been no disruption to scientific output. Realignments within the
Laboratories of Genetics, Chemistry and Biophysics are underway to bring these
programs into sharper focus for more effective scientific progress.

Within the Laboratory of Genetics, progress has been made to provide a better
□nderstanding of the mechanisms of chemical mutation, to develop better mutation
detection methods, and to understand the effects of mutations on human health.
Investigators have found that within areas of the DNA where there is a naturally
high rate of mutations, there are short unpaired nucleotides which loop out of
the DNA's helix. This structure is common to several of the lower species and
NIEHS geneticists are looking at mammalian cell DNA to see if the structure is
present there as well. At a molecular level, scientists are attempting to
define the types and amounts of variability in populations of eukaryotic
organisms, while other studies have involved the spontaneous mutations of the
white locus in Drosophila , which are the results of insertions of transposable
sequences of DNA of unknown origin and function.

During routine screening for mutations in mice by the Laboratory's mutagenesis
screening program scientists discovered a mutant gene in mice similar to the
one that causes Beta thalassemia (Cooley's Anemia) in humans. The discovery
has led to the development of a mouse strain that can be used for in vivo
research on this heritable disease. The mutation, discovered in association
with scientists outside the Institute, is designated Hbb^"~' and represents the
only available animal model for studying Beta thalassemia and points out the
importance of routine mutagenesis screening.

Within the Institute's Extramural Program, there have been new discoveries
related to effects of air pollution from burning coal and the undesirable
effects of kerosene space heaters on indoor air. Research at the Environmental
Health Sciences Center at MIT has shown that when coal is burned when the
humidity is high, two pollutants— sulfur dioxide and zinc oxide - combine to
form aerosol by-products that are more toxic than either of the compounds
separately. The particles, which are coated with sulphuric acid, sulfates or
sulfites, when they are inhaled by laboratory animals, restrict the amount of
oxygen absorbed in the blood. This discovery could lead to modifications in
power plant design that would further protect human health from the dangers of
smoke stack effluent. Studies at the Yale School of Public Health have found
that under certain conditions indoor kerosene space heaters can create levels
of nitrogen oxide, sulfur dioxide, carbon monoxide and carbon dioxide that
exceed ambient air quality standards set for outdoors under the Clean Air Act
and in some instances exceed OSHA standards for allowable workplace exposures.



A new research development award, the Clinical Investigator Award in environmental
health research, was announced this year. This five-year award is designed to
provide intensive guided research experience for clinicians. It will provide
up to three years of guided research experience under an established investigator
plus two years of additional research support during which time the awardee
will be expected to develop a program of clinical research within his or her
own department.

Research is being conducted under an Interagency Agreement with the Lawrence
Livermore Laboratories to determine how cooking various types of foods produces
mutagens which might be precursors to cancer. Researchers found that protein
rich foods such as beef, pork, and veal become highly mutagenic when grilled or
broiled at high temperatures. Knowledge of the relationship between mutagenesis
and carcinogenesis increases, and as we combine this information with what we
know about the correlation of rates of different types of cancers and different
diets around the world, our increased understanding of food chemistry may be
useful in developing diets that will lower our risk from some cancers.

A major portion .of the Institute's efforts applied to the National Toxicology
Program through its Toxicology Research and Testing Program is extending the
endpoints of its bioassays to include information on hepatotoxicity, nephro-
toxicity, teratogenicity, mutagenicity, toxic effects on the immune system,
lungs, etc. Studies are now routinely performed to help understand the
absorption, distribution, and excretion of chemicals at various concentrations.
NTP also conducts several types of short-term tests to determine the chemical's
effect on the genome.

Traditional testing practices are being examined to determine if there are ways (
to reducing their costs without compromising quality.

The Breast Milk and Formula Project, an epidemiologic study within the State of
North Carolina on the effects of PCBs and DDE on the offspring of over 800
nursing mothers, is producing some interesting information. Some of the mothers
participating in the study had been accidentally exposed to PCBs illegally
dumped along highways in North Carolina. While the overall level of PCBs found
in their milk was not different from what is normally found, one particular PCB
in their milk was identified as being similar to that dumped along the roadway,
indicating that a small amount of the chemical had likely been absorbed from
the spill .



GENETICS



OFFICE OF THE ASSOCIATE DIRECTOR FOR GENETICS
Summary Statement

During FY 1983 the Office of the Associate Director for Genetics (OADG)
continued to fulfill its role in the Genetic Toxicology programs of the
Institute by serving as an expert consultant to the Director and the
intramural research staff and by developing programs in the areas of
genetics and environmental mutagenesis. The OADG has provided a focal
point as well as planning and coordination functions in a number of areas
of genetic toxicology including (1) international programs, (2) national
programs, (3) committees, (4) collaborative studies and (5) collaborative
research programs.

International Programs

US-Japan

The Associate Director for Genetics (ADG) is Chairman of the US Panel on
Environmental -Mutagenesis and Carcinogenesis in the US-Japan Cooperative
Medical Science Program. The lOth Joint Conference of the Panel was held
in Honolulu, Hawaii, February 7-9, 1983 on the topic of Population Mon-
itoring: Methods and Applications. A total of 5 sessions were held on
the topics: (1) Evaluation of Reproductive Effects and Spontaneous Abor-
tions, (2) Evaluation of Chromosome Damage, (3) Urine and Semen Anaysis,
(4) Population Monitoring: New Methods and Surveillance and (5) Population
Monitoring and Future Directions.

ICPEMC

The Associate Director for Genetics attended the meeting of the Executive
Board and Commission of the International Commission for Protection Against
Environmental Mutagens and Carcinogens (ICPEMC) held in Thonon, France,
April 16-22, 1983. The meeting was devoted to planning of future programs
of the Commission and proposed workshops on Retinoblastoma and Down's Syn-
drome. There were discussions regarding relations between the International
Program for Chemical Safety (IPCS) and ICPEMC and future cooperative activ-
ities.

Egypt

At the invitation of the Department of Botany, Faculty of Agriculture,
University of Zagazig, Zagazig, Egypt, the ADG served as visiting professor
from October 29 - November 15, 1982. He presented a series of lectures at
the University of Zagazig as well as in Cairo at the National Research
Center, Ain Shams University and Cairo University. He also consulted with
faculties and researchers regarding possible participation in the IPCS.

National Programs

EPA Gene-Tox Program

The ADG has participated in several periodically held meetings of the Co-
ordinating Committee during the second phase of the program. The purpose



of this phase is for the various Assessment Panels to evaluate the utility
of the various test systems, cross-indexing of the data and recommendations
of appropriate batteries of tests for mass screening. The Coordinating
Committee reviews the reports of the Panels and reviews the feasibility
of panel activities in terms of the computerized data base.

NIEHS Sponsored Workshops

The OADG organized a conference on "Genetic Consequences of Nucleotide
Pool Imbalance" which was held at NIEHS on March 9-11, 1983. Participation
in the meeting included several NIEHS staff, as well as Foreign and American
researchers active in this new area of study. Proceedings of the conference
are in the process of being published.

The Proceedings of the NIEHS Workshop on "Utilization of Mammalian Specific
Locus Studies in Hazard Evaluation and Estimation of Genetic Risk" were
published in July, 1983. The book is edited by the ADG and Dr. William
Sheridan.

Seminars

The ADG, in collaboration with Intramural Research Program staff, has
developed a seminar series entitled "New Frontiers in Genetics" for the
purpose of inviting scientists whose research is the vanguard of advances
in their field of genetics to present their work to the NIEHS scientific
staff. Lectures dealing with molecular genetics, advanced cytogenetics,
and monoclonal antibodies have been given by such eminent scientists as
William Engels, Jorge Junis, and Paul Lohman.

Commi ttees

Subcommittee on Environmental Mutagenesis - The ADG continues to chair the
DHHS/CCERP Subcommittee on Environmental Mutagenesis. Topics covered
included: a review of the NIEHS portion of the National Toxicology Program,
Genetic Effects of Ethylene Oxide, Genetic and General Toxicology of
Benzene, The Love Canal Cytogenetics Study, and Mutagens from the Cooking
of Food. These and other current issues of importance to government
agencies concerned with genetic toxicology will continue to be addressed
by the Subcommittee.

The Committee for Hazard Evaluation and Risk Estimation - which was organ-
ized and is chaired by the ADG, continues to meet on a monthly basis to review
experimental methodologies and techniques, current literature and recent
results, for their suitability for estimation of risk.

Collaborative Studies

WHO - International Program for Chemical Safety

The ADG is chairman of a working group of the International Program for
Chemical Safety (IPCS) sponsored by the World Health Organization, the
United Nations Environmental Program and the International Labor Organ-
ization. A meeting of the working group was held in Geneva, Switzerland,
May 16-18, 1983, to conduct a review of the status of Part I (in vitro)



and to further plans for Part II (in vivo) of the IPCS study on short-
term tests for genotoxicity and carcinogenicity. Plans for a meeting of
the investigators participating in Part I, to be held at St. Simons Island,
Georgia in October, 1983, were developed. This meeting will consist of
a series of assay systems workshops to evaluate the results which have
been obtained and to prepare workgroup reports.

Collaborative Research Programs

Illinois State University

The Principal Investigator continues to submit reports on chemicals tested
under the contract. In addition, reports are being received regarding tests
to make the mutants recovered homokaryotic as well as reports on more de-
tailed genetic analysis. The data generated during the period that the
contract was in force are being utilized as the basis for scientific reports
which continue to be prepared for publication.

Public Lectures

F. J. de Serres

1. New York Academy of Sciences Conference on Cellular Systems for Tox- •
icity Testing, New York, NY, October 5-7, 1982, "The Role of Neurospora

in Evaluating Environmental Chemicals for Mutagenic Activity".

The following five lectures were presented by the AD6 during his Egyptian
visit, October 29 - November 15, 1982:

2. "The Role of Neurospora in Evaluating Chemicals for Mutagenic Activity"

3. "The Use of Tradescantia in Monitoring for Mutagenic Air Pollutants".

4. "Interaction and Mutation Induction in Wild-type and Repair Deficient
Haploid Strains of Neurospora crassa ".

5. "International Program for the Evaluation of Short-term Tests for
Carcinogenicity (IPESTTC)".

6. "Mutagen Specificity in Wild-Type and Repair Deficient Two-Component
Heterokaryons of Neurospora crassa " .

7. Mary Ann Swetland Program in Medicine and Human Behavior, Case
Western Reserve University, Cleveland, OH, January 10, 1983 "Evaluation
of the Utility of Short-term Tests for Carcinogenicity and Mutagenicity".

8. 14th Annual Meeting of Environmental Mutagen Society, San Antonio,
TX, March 3-6, 1983, "Induction of ad-3 Mutants in Nucleotide Excision-
Repair Deficient Strains Provides Evidence for Qualitative Differences

in the Spectrum of Genetic Alterations from that found in Wild-Type Strains
of Neurospora crassa " .



9. NIEHS Conference on Genetic Consequences of Nucleotide Pool Imbalance,
NIEHS, Research Triangle Park, NC, May 9-11, 1983 "Base Analog Mutagenesis
in Neurospora" .

10. The Gordon Conference on Genetic Toxicology Bioassays, New London, NH,
June 27-July 1, 1983 "The Evaluation of Short-Term Tests for Carcinogens

in the International Program for Chemical Safety".

William Sheridan

1. 14th Annual Meeting of Environmental Mutagen Society, San Antonio, TX,
March 3-6, 1983, "Effects of Tri ethyl enemel amine (TEM) Exposure on Fetal
Germ Cells of Male Mice".



10



OFFICE OF HEALTH HAZARD ASSESSMENT



11



OFFICE OF HEALTH HAZARD ASSESSMENT
Suminary Statement

The main function of this office remains the evaluation of human health hazards,
particularly from chemicals in man's environment, both newly introduced and
those already used in agriculture, industry and in the home as components of
food, beverages and consumer products, as well as air, water, food and soil con-
taminants. In addition, the office has given increased attention to the
assessment of methods for testing and for the control of exposure to chemicals.

Human exposure can occur directly through skin contact or ingestion or
indirectly through environmental media. The chemical form, biological availabi-
lity and concentration of chemicals may change in their passage through the
environment. They may be degraded to less toxic substances or may be trans-
formed to more 1:oxic compounds. They may accumulate selectively in some orga-
nisms and their concentrations may become many times higher than those found in
contaminated water or soil. On the other hand, they may be eliminated from
water or air by various physical processes. Secondary pollutants can be formed
by chemical or biochemical reactions. Some chemicals are stable and may persist
in the environment for a long time. Examples are polychlorinated dibenzodioxins
which occur as contaminants of some herbicides such as 2,4,5-trichlorophenoxy
acetic acid, and polychlorinated biphenyls.

Mutagenic potential is well-established for many chemicals, mainly as a result
of in vitro testing. Further research, particularly on the mechanisms of DNA
repair inhibition, is needed to assess the possible role of environmental chemi-
cals in human genetic disease. Pathophysiological processes induced by exposure
to chemicals may involve a complex chain of changes that develop gradually and
are not detected for a long time. A long latency period characterizes the
effects of some substances so that the time from the first exposure to the deve-
lopment of a clinically detectable cancer can exceed 20 or 30 years. In addi-
tion, man is rarely exposed only to a single chemical; a better knowledge of the
effects of mixtures and of host and environmental factors that may modify the
outcome of exposure would greatly improve the possibility of controlling
diseases that are either induced or promoted by chemicals.

In most cases, the assessment of health hazards is based on data from animal
experiments. This presents difficulties because methods for testing are not
uniform, and animals may not respond to chemical exposure in the same way as
human subjects; groups of animals exposed in laboratory tests are small and
homogeneous compared to large heterogeneous human populations which include very
young and very old persons, those that are healthy and those that suffer from
various diseases. Thus, the assessment of existing methods for testing chemi-
cals and identification of their short -comings is essential for developing
better methods for risk estimation in humans. This applies in particular to
methods for testing and evaluating mixtures of chemicals.



13



To assist in the selection of chemicals for the National Toxicology Program
(NTP), all members of OHHA and Ors. D.B. Walters, TRTP, and B.A. Fowler, LP,
have continued to participate in the NIEHS Subcommittee of the NTP Chemical
Nomination and Selection Committee, which has been chaired this year by Dr.
Piver. Dr. Vouk has remained a member of the MTP Toxicology Design Committee.

OHHA staff also contributes to the preparation of the Annual Reports on
Carcinogens. Because of a prolonged absence of the Assistant Director for
Toxicology Coordination, Dr. Vouk coordinated the final review and revisions of
the Third Annual Report.

Collaboration with the World Health Organization (WHO) has continued both within
the framework of the International Programme on Chemical Safety (IPCS) and other
WHO programs in environmental health, MIEHS being a WHO Collaborating Center on
Environmental Health Effects. OHHA has been responsible for NIEHS's contribu-
tions to and review of IPCS draft evaluations of priority chemicals and toxico-
logical methods. As a WHO temporary adviser, Dr. Vouk stayed three weeks in
Geneva in April and prepared a draft working paper on organizational arrange-
ments of the IPCS, and participated in consultation on the same subject held
in Geneva in July. Drs. Vouk and Piver participated in a Workshop on methods of
toxicological testing and evaluation of mixtures of chemicals in Guildford,
England, in August. Dr. Vouk also participated in the Conference on
Environmental Research and Management Priorities in the 1980's organized by the
Royal Swedish Academy of Sciences in Rattwick, Sweden, in November 1982.

The Associate Director spent most of the fiscal year away from the office due to
a series of illnesses. Because of that, he attempted to complete his obliga-
tions to other organizations. He completed his term as member of the Scientific(
Advisory Panel for the Chemicals Industry Institute of Toxicology (CUT) and
terminated his functions as Chairman of the Visiting Committee to the Brookhaven
National Laboratory's Medical Division.

His membership on the International Joint Commission's Committee on the
Assessment of Health Effects of the Great Lakes Water Quality had to terminate
this summer. This year saw the results of a research project carried out by
Cornell Univeristy's Drs. Ronald Brickman, Sheila Jasanoff and Thomas Ilgen. A
book entitled Chemical Regulation and Cancer: A Cross-national Study of Policy
and Politics was published for which the Associate Director had served as advi -
sor.

The work of OHHA was supervised by Dr. Warren T. Piver as Acting Associate
Director for the first half of the fiscal year and by Dr. Velimir B. Vouk as
Acting Director, OHHA, for the second half.



(



DEPARTMENT OF HEALTH AND HUMAN SERVICES - PUBLIC HEALTH SERVICE
NOTICE OF INTRAMURAL RESEARCH PROJECT



I PROJECT NUMBER

Z01 ES 20002-11 OHHA



PERIOD COVERED

October 1, 1982, to Seotenber 30, 1983



TITLE OF PROJECT tSO charadera or len. Title mutt fit on one line between the bordert.)

I Technology Forecasting and Technology Assessnent



PRINCIPAL INVESTIGATOR (Liit other profetMionai personnel on tubtequent paeet.)
\(Name, title. laiorotory, and institute affiliation^

Wa rren T. Pjver Chemical Engineer



OHHA iNIEHS



COOPERATING UNITS (if any)



LAB/BRANCH

Office of the Director (00'



SECTION

Office of Health Hazard Assessment (OHHAl



INSTITUTE ANO LOCATION

NIEHS, NIH. Research TrianoTe Park. N. C. 2770Q



TOTAL MANYEABS:



i.-o



PROFESSIONAL:



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0.0



CHECK APPROPRIATE aOX(ES)

□ (a) Human subjects □ (b) Human tissues

□ (al) Minors
D (a2) Interviews



Sn (c) Neither



SUMMARY OF WORK (Use standard unreduced type. Da not exceed the space prauided.)

Because subsurface burial of industrial chemicals has been a common method
of waste disposal, a mathematical model describing the simultaneous transfer
of heat, moisture, and chemicals in unsaturated and saturated soils was



Online LibraryNational Institute of Environmental Health ScienceAnnual report : National Institute of Environmental Health Sciences (Volume 1983) → online text (page 1 of 89)