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Annual report : National Institute of Environmental Health Sciences (Volume 1987) online

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NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES



FY 1987 INTRAMURAL RESEARCH PROJECTS
October 1, 1986 through September 30, 1987



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CONTENTS

OFFICE OF THE DIRECTOR 3

Office of the Assistant to the Director for International Programs ... 7

Office of Facilities Engineering 23

Health and Safety Office 13

Library and Information Services Office 19

DIVISION OF INTRAMURAL RESEARCH

Office of the Scientific Director 29

Laboratory of Behavioral and Neurological Toxicology 33

Laboratory of Genetics 53

Laboratory of Molecular Biophysics 89

Laboratory of Pharmacology 119

Laboratory of Pulmonary Pathobiology 127

Laboratory of Reproductive and Developmental Toxicology 139

Comparative Medicine Branch 153

DIVISION OF BIOMETRY AND RISK ASSESSMENT

Office of the Program Director 163

Computer Technology Branch 167

Epidemiology Branch 171

Laboratory of Biochemical Risk Analysis 185

Statistics and Biomathematics Branch 197

DIVISION OF TOXICOLOGY RESEARCH AND TESTING

Office of the Program Director 207

Carcinogenesis and Toxicology Evaluation Branch 213

Cellular and Genetic Toxicology Branch 227

Chemical Pathology Branch 249

Systemic Toxicology Branch . 259

INTRAMURAL PROJECT NUMBER LISTING 288

i



OFFICE OF THE DIRECTOR



OFFICE OF THE DIRECTOR

The National Institute of Environmental Health Sciences celebrated its Twentieth
Anniversary Year in 1987, simultaneous with its participation in the Centennial
observances of the National Institutes of Health. Today the Institute has
reached a critical mass of personnel and expertise to carry out a broad-based
program in environmental health sciences. NIEHS has the principal
responsibility among Federal agencies for the support of research and training
of research manpower concerned with the effects of chemical, physical and
biological factors on human health. The emphasis in this work is to find the
mechanisms of toxicity of environmental agents at the molecular and cellular
levels. This year, as in past ones, technology and science have continued to
open new doors to the researchers who seek to elucidate the complex way the body
maintains health or falls prey to disease following exposure to environmental
agents.

Advances in technology such as computer enhanced magnetic resonance spectroscopy
and imaging, the dazzling progress in the field of genetics, and the
increasingly sophisticated application of x-ray and scanning electron
microscopy, among many such examples, continually offer researchers new insights
and opportunities. Since its inception. Institute investigators have published
almost 4,000 articles in the scientific literature making the results of their
research known to the scientific community at large, and adding greatly to the
knowledge base. This information is used by regulatory agencies, the medical
community and other concerned groups to develop and initiate appropriate
standards for public health programs.

While the Institute took time to look back at its history, challenging
opportunities for the future became apparent this year. The Superfund
Amendments and Reauthorization of 1986 authorized two new grant-supported
programs at NIEHS, one for university-based basic research and training, the
other for health and safety training of workers at hazardous waste sites and for
emergency response personnel. These programs have been developed and
implemented, including conducting the technical/scientific merit review of 79
complex applications submitted in response to two solicitations.

This year, the Department of Health and Human Services approved the
redesignation of all the major organizational components within NIEHS, elevating
the four Program areas to Division status.

The Division of Intramural Research concentrates on understanding the myriad
wa^s in which environmental factors enter the body and disrupt its normal
functions. The research ranges from experiments with isolated molecules such as
DNA using sophisticated molecular biology techniques, to monitoring the levels
of calcium ion in the beating heart of a living animal. The latter studies
utilize nuclear magnetic resonance (NMR) a procedure requiring instruments
housed in special facilities devoid of ferrous-containing materials. A new NMR
facility, completed this year, will greatly expand our capacity to carry out
non-invasive research on whole animals.

The Division of Biometry and Risk Assessment utilizes epidemiological studies
and mathematical models in conjunction with toxicological studies of the
underlying biological mechanisms to evaluate the risks of various chemicals.



A major focus of the research effort is the qualitative and quantitative
estimation of adverse health effects resulting from exposure to hazardous
environmental agents, with particular emphasis on the development of methodology
useful in this estimation process. Using recent advances in genetic engineering
and sophisticated new computer modeling technologies scientists have been able
to examine DNA interaction at the molecular level and look at the mutational
"hotspots" within DNA sequences that appear to play an important role in causing
cancer. Researchers in this Division are making exciting progress in
delineating the characteristics and action of oncogenes (chemical causing
genes). They are investigating how chemicals activate normal genes into
oncogenes and how this activation process is involved in the induction of
tumors. Such information will enhance the use of data from animal toxicology
studies for risk assessment and improve the basis for decisions on regulating
human exposure to workplace and other environmental chemicals.

The Division of Toxicology Research and Testing is the core of the National
Toxicology Program (NTP) and through its basic toxicologic studies provides much
of the scientific information used by regulatory and public health intervention
and prevention agencies to understand which chemicals may be public health
hazards and what types of efforts must be implemented to prevent or reduce
harmful exposures. The NTP uses state-of-the-art methods and, on an ongoing
basis, examines, develops, and validates new, improved technologies. Those
found to offer improvement over older methods are selected for further
investigation and perhaps validation. Scientists from this and another
Division have published a landmark study that places in perspective the limits
of short term toxicological tests as predictors of carcinogenicity in rodent
studies. Their analyses produced strong evidence that such tests, at their
current state of development, are not an efficacious substitute for whole animal
research.

The Division of Extramural Research and Training funds research and training in
numerous environmental science disciplines throughout the country. Utilizing
investigator initiated research grants and program projects, centers,
fellowships, training grants and other mechanisms of financial support,
scientists at universities and research centers concentrate on the prevention,
diagnosis and treatment of a variety of environmentally induced diseases. Many
of the current standards for lead exposure have been based upon research
supported by NIEHS. The information developed by NIEHS grantees has influenced
legislation on lead-based paint, guidelines for screening of lead levels in
children, and Federal regulations on lead in gasoline. Currently supported
research is discovering subtle neurobehavioral effects in children from exposure
to levels previously thought safe. The possible implications for a generation
of children is frightening.

These NIEHS research programs will continue to evolve, taking advantage of new
knowledge. Today, because of advances in the environmental health sciences, we
understand more about the mechanisms by which toxins cause disease. We have
broadened our inquiry from looking at specific diseases or conditions such as
cancer, birth defects or target organ damage to looking at the whole person.
Our scientists now know that potentially toxic chemicals can affect the entire
biological system and that many of these effects are subtle ones, and much more
far reaching than originally thought. It appears that when these chemical
toxins interrupt any one of the normal body processes, they create problems in
other parts of the system in ways that we do not yet fully understand. We have



learned that the human body is a complex communications network that cannot
function properly when any one major piece is not working properly.

Through a continually improving understanding of environmental agents, and how
they affect human health, wiser choices can be made about how we live and work.
With an expanded knowledge of environmental health sciences, more prudent
regulations, legislation and public health policy can protect the air, water,
soil and food sources on which we depend. Errors made in the past and lack of
understanding about the by-products of technology have proven to have a
substantial effect in the present. The research conducted today, and the
decisions based upon it may well prove crucial to the health and happiness of
our own old age, and the futures of our children, grandchildren and their heirs,



INTERNATIONAL PROGRAMS
OFFICE OF THE ASSISTANT TO THE DIRECTOR FOR INTERNATIONAL PROGRAMS

Summary Statement

The Office of the Assistant to the Director for International Programs is
responsible for the following areas:

I. INTERNATIONAL PROGRAMS

NIEHS conducts scientific exchanges and collaborative research through
a variety of mechanisms that extend from informal contact between
investigators in a number of countries to formal bilateral and multilateral
agreements for cooperation between the U.S. and the governments of other
countries.



Cooperation with the World Health Organization (WHO)

NIEHS has been designated by WHO as a Collaborating Center for
Environmental Health Effects since 1975. As a Collaborating Center,
NIEHS provides advice and scientific expertise to WHO headquarters and WHO
Regional Offices, and assists them in formulating research programs
related to the biomedical aspects of environmental pollution.

In 1979, WHO established the International Programme on Chemical Safety
(IPCS) a cooperative undertaking involving WHO, the United Nations
Environmental Programme, the International Labor Organization, and their
Member States. In October 1980, a cooperative agreement was signed
between NIEHS and WHO, and NIEHS assumed the function of a Participating
Institution (PI) within the IPCS for such activities as international
evaluation of the biological effects of chemicals and health hazard
assessments, and review and/or validation of methods for testing of
mutagenicity, carcinogenicity, neurobehavioral toxicity, and toxicity to
reproductive function. In September 1986, the Agreement was extended for
another three years. A WHO Interregional Research Unit (IRRU), housed at
NIEHS was established in 1981 to assist the Central Unit established at
WHO headquarters in coordinating the activities of the IPCS/PI's. During
1987, NIEHS hosted an informal meeting of representatives of IPCS-PI's
from the American Region. The Director, Environmental Health, WHO, and
the Manager, IPCS, reviewed the activities of the IPCS and the Pis
discussed their work related to the objectives of the IPCS. The meeting
greatly facilitated an exchange of information and hopefully will lead to
joint activities between Pis under the IPCS umbrella.

Since the inception of the Programme, numerous scientific experts from
NIEHS have participated on IPCS committees, special consultations,
conferences, and technical working groups. The Director, NIEHS, serves as
a member of the IPCS Programme Advisory Committee (PAC) and chaired the
PAC during the Programme's first two years of operation. This Committee,
composed of members designated by the Director-General of WHO, is the
general oversight body providing advice on the policies and priorities of
the IPCS. The Fifth PAC met in Geneva in FY 1987. The Director, NIEHS,



attended this meeting and the Assistant to the Director for International
Programs served as Rapporteur. A number of NIEHS scientists continue to
play a leading role in the IPCS Collaborative Study on Short-Term Tests
for Genotoxicity and Carcinogenicity. Institute scientists also
participated in the preparation of the monographs on (1) Principles and
Methods for Evaluating the Neurotoxicity of Chemicals; (2) Toxicokinetics;
(3) Principles and Methods for Evaluating the Toxicity of Chemicals - Part
11; (4) Manual on Epidemiological Methods; (5) Approaches Needed to
Establish the Role of Chemical Agents in the Etiopathogenesis of Certain
Non-Conmuni cable Diseases and (6) Immunotoxicology. Also, during 1987,
NIEHS staff continued to review IPCS criteria documents, working papers,
and proposed projects.

The objectives of the IPCS are: (1) to encourage international
cooperation in the evaluation of the effects of chemicals on human health
and on the quality of the environment; (2) to coordinate chemical testing
and toxicological research to eliminate unnecessary duplication of
efforts; (3) to develop international protocols for laboratory testing,
epidemiological studies, and risk assessment; (4) to develop international
guidelines and exposure limits for chemicals in air, water, and food and
limits for hazardous chemicals in workplaces; (5) to develop response
mechanisms for coping with chemical emergencies which may be international
in scope; and (6) to promote training and development of manpower in areas
of specialties necessary for the achievement of program goals. The IPCS
provides an effective multilateral mechanism for dealing with global
environmental health issues and avoiding costly duplication of national
efforts to test and assess chemicals.

During FY 1987, NIEHS staff also participated in the International Meeting
of the Scientific Group on Methodologies for the Safety Evaluation of
Chemicals (SGOMSEC) dealing with methods to reduce injury due to chemical
accidents. Also, the Director, NIEHS, and the Assistant to the Director,
NIEHS, participated in a SGOMSEC planning meeting in 1987 to outline the
workshop on "Methods to Assess the Adverse Effects of Pesticides on
Non-Vector Targets," to be held in Czechoslovakia in 1988. SGOMSEC is an
IPCS activity sponsored jointly with the Scientific Committee on Problems
of the Environment of the International Council of Scientific Unions.

NIEHS also collaborates with the WHO International Agency for Research on
Cancer (lARC). Collaborative efforts include the establishment of a
registry of workers exposed to particular pesticides which contain dioxin
contaminants. During FY 1987, scientists from NIEHS and the U.S. National
Toxicology Program (NTP) participated in a number of lARC sponsored expert
working groups to prepare "lARC Monographs on the Evaluation of
Carcinogenic Risk of Chemicals to Humans." These monographs collect all
available relevant experimental and epidemiological data about a chemical
or groups of chemicals to which humans are known to be exposed, and
summarize the evidence for the carcinogenicity of chemicals and other
relevant information.

US-China (Mainland) Cooperation

Cooperation between the United States and the People's Republic of China
in the area of environmental health was initiated during 1980 under the



US-PRC Agreement for Cooperation in the Science and Technology of Medicine
and Public Health. NIEHS is a participant in the topic on public health
and health services research, which includes concerns relating to
environmental and occupational health. Exploratory discussions between
both sides have been held during exchange visits with initial discussions
centering around cooperation in the following areas: reproductive and
developmental toxicology, validation of short-term test methods to detect
and assess carcinogens, mutagens, and teratogens in the environment; and
the extrapolation of laboratory animal data to man. NIEHS scientists have
given research seminars at various institutions in the People's Republic
of China, and have hosted the visits of numerous Chinese scientists to
discuss research programs of mutual interest. During 1987, the Director,
NIEHS, was the DHHS delegate to the U.S.-P.R.C. Joint Commission on
Science and Technology meeting held in Beijing. The status and progress
of various collaborative areas were reviewed and potential new areas
of cooperation identified.

US-China (Taiwan) Cooperation

Collaborative studies between U.S. and Taiwanese scientists are carried
out through a Cooperative Program in the Biomedical Sciences between the
American Institute in Taiwan and the Coordinating Council for North
American Affairs. For the past five years, NIEHS scientists from the
Biometry and Risk Assessment Program have collaborated with Taiwanese
scientists in studies investigating the effects of accidental human
exposure to polychlorinated biphenyls (PCBs) in Taiwan. Studies on the
effects of PCB exposure on enzymatic activity in human tissues suggest a
potential for substantial and persistent effects of these pollutants on
human metabolism. NIEHS epidemiologists in collaboration with Taiwanese
scientists are conducting a clinical evaluation of a cohort of children
exposed transplacentally to PCBs and related chemicals. Preliminary data
show that the children have abnormalities of pigment, nails, teeth, and
skin; and show a developmental delay on a number of dimensions. The data
is being analyzed and further followup of this cohort is being considered.

US-Egypt Cooperation

Cooperation between American and Egyptian environmental health scientists
is being carried out under the auspices of a U.S. -Egypt Joint Working
Group on Health Cooperation (JWGHC), supported by the U.S. Agency for
International Development. NIEHS has been assigned responsibility for the
U.S. Subcommittee on Environmental and Occupational Health of the JWGHC.
Efforts are continuing in the establishment of an Information Unit for
Environmental Impact Assessment. This Information Unit, located at the
Environmental Health Center in Cairo, provides the Egyptian Ministry of
Health and Egyptian institutions and universities with access to U.S.
information on environmental and occupational health hazards, thus
strengthening the scientific base for research and regulatory decision
making.



US-FinTand Cooperation

A Memorandum of Understanding on Collaboration between NIEHS and the
Finnish Institute of Occupational Health, Helsinki, was formalized in
November 1982. Since then a number of exchange visits have taken place
between U.S. and Finnish scientists to exchange information on
pharmacokinetics, reproductive toxicology, neurobehavioral toxicology,
genetic toxicology, epidemiology and risk assessment, and strategies for
toxicological research priority settings.

US-India Cooperation

NIEHS and NTP scientists are cooperating with India by conducting
experimental animal studies on the toxicity of methyl isocyanate, the
chemical responsible for the world's worst industrial disaster which
occurred in Bhopal , India in December 1984. Several NIEHS scientists
have visited research and government organizations in India to discuss
NTP's research findings on the toxicity of methyl isocyanate. NIEHS also
hosted the visits of a number of scientists from India to discuss
toxicological research activities.

US-Italy Cooperation

Cooperation in environmental health research between American and Italian
health scientists has taken place since 1977 under a Memorandum of
Understanding between the U.S. Department of Health and Human Services and
the Italian Ministry of Health. Since then a number of exchange visits
have taken place to exchange information on the bioavailability of
2,3,7,8-tetrachlorodibenzodioxin, studies on the chemical contamination of
drinking water, chemical selection procedures, and the design of two-year
toxicity studies.

US-Japan Cooperation

Cooperation between American and Japanese scientists on environmental
health problems takes place under two formal agreements: The US-Japan
Cooperative Medical Sciences Program and the Agreement on US-Japan
Cooperation in Research and Development in Science and Technology. Under
the US-Japan Cooperative Medical Sciences Program, American environmental
health scientists participate in the Panel on Environmental Mutagenesis
and Carcinogenesis. The Director, Division of Biometry and Risk
Assessment, NIEHS, serves as a member of the Panel; and the Assistant to
the Director for International Programs, NIEHS, serves as the Panel's
program officer. Joint areas of research focus on the detection of
mutagenic and carcinogenic chemicals using both in vitro and i_n vivo test
systems, and on monitoring human populations for evidence of exposure to
mutagenic and carcinogenic chemicals. The Director, NIEHS, serves as a
State Department appointed member of the Joint Committee which oversees
the overall activities of the US-Japan Cooperative Medical Sciences
Program. This Joint Committee meets annually, alternating between the
U.S. and Japan. During FY 1987, the Director, NIEHS; and the Associate
Director for Genetics, NIEHS; and the Assistant to the Director for



10



International Programs, NIEHS, participated in the 15th US-Japan Joint
Environmental Panel Conference on "Approaches for Human Population
Monitoring", held at Lawrence Livermore National Laboratory, Livermore,
California. Also, during 1987, the Director, NIEHS, participated in the
US-Japan Joint Subcommittee Meeting on Program Review and Planning, and the
23nd US-Japan Joint Committee Meeting.

Under the US-Japan Agreement on Cooperation in Research and Development in
Science and Technology, NIEHS participates in the toxicology program area
in the counterpart working group on health. Cooperative activities under
this agreement focus on the testing of chemicals for mutagenic,
carcinogenic, and other toxic effects. In FY 1987, annual exchange visits
between Japanese and NIEHS scientists continued, and both sides have
shared information on test method development, which chemicals will be
tested, and test results. Several test systems are being reviewed and
validated in both U.S. and Japanese laboratories, and collaborative
activities on oncogenes have been initiated.

US-USSR Cooperation

Collaboration between Soviet and American environmental health scientists
is carried out under the auspices of two cooperative agreements between
the United States and the Soviet Union. Under the Medical Science and
Public Health Cooperative Agreement, scientists from both countries are
conducting joint research on the biological effects of low frequency
electromagnetic radiation. 1987 was the fifteenth year of formal
collaboration in environmental health research between the U.S. and
U.S.S.R. Cooperative research efforts have involved formal workshops and
exchange visits between scientists of both countries. Duplicate
collaborative experiments aimed at evaluating sensitive tests for
determining the biological effects of electromagnetic fields on the
nervous system and to validate research results obtained in the U.S. and
the Soviet Union have been completed. A large amount of scientific
information has been exchanged during these collaborative activities.

NIEHS also participates in the US-USSR Agreement on Cooperation in the
Field of Environmental Protection which is administered for the United
States by the Environmental Protection Agency. The Director, NIEHS,
serves as DHHS representative to the Environmental Protection Agreement
and co-chairman of the working group concerned with the biological and
genetic effect of pollution. Exchange visits under this Agreement have
been conducted in research areas concerned with the mutagenic effects of
environmental contaminants.

US-Yugoslavia Cooperation

Under the auspices of the US-Yugoslavia Joint Board for Scientific and
Technological Cooperation, NIEHS scientists continued collaborative
studies in 1987 on the evaluation of the genetic effects of low levels of
environmental chemical mutagens in bacterial systems, and comparison with
eukaryotic cells.



11



II. INTERAGENCY COORDINATION

A number of federal and state agencies are involved in collaborative
efforts to establish integrated systems for gathering, evaluating, and
disseminating information on the health and environmental effects of
chemical substances. The Assistant to the Director for International



Online LibraryNational Institute of Environmental Health ScienceAnnual report : National Institute of Environmental Health Sciences (Volume 1987) → online text (page 1 of 31)