&EPA
   United States
   Environmental Protection
   Agency
   National Health and
   Environmental Effects Research
   Laboratory

   Science Report
   Volume 1, Issue I
   December 2001

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                               CONTENTS

Click on title to link directly to article.

RESEARCH
                                                                    Page
Lung Inflammation Correlated with PM Exposure in Humans	

Ecological Effects Database Available on the Internet	

Field Tests Held on Ocean Response Coastal Analysis System	

Mechanisms Probed for How Dioxin Causes Birth Defects in Mice	
Stream Conditions Assessed by Sampling Biology	

Toxicity Studies on Brominated Flame Retardants Under Way	

PUBLICATIONS

Proceedings Issued on Risk Assessment Indicators	

Booklet on Ecological History of New Bedford Harbor Published . . .

Proceedings Issued on Microbes and Disinfection By-products in Drinking Water.

New England Climate Change Report Published	

MEETINGS / CONFERENCES

International Symposium on Polycyclic Aromatic Compounds Held	

International Breast Cancer Meeting Held	

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                                 RESEARCH

Lung Inflammation Correlated with PM Exposure in Humans

      A clinical study has found that lung inflammation in humans from exposure to
particulate matter (PM) can be associated with increases in hospitalizations and
respiratory illnesses observed in epidemiology studies. The study is the first to
demonstrate such a correlation and has been reported in the August 15, 2001, issue of
American Journal of Respiratory and Critical Care Medicine by Drs. Andrew Ghio and
Robert Devlin of NHEERL's Human Studies Division.  The controlled-exposure study of
healthy young adult volunteers is described in an article entitled "Inflammatory Lung
Injury after Bronchial Instillation of Air Pollution Particles."

      During the 1980s, the Utah Valley near Provo had high PM  levels, with the
principal point source being a steel mill.  While operational, the mill contributed more
than 80 percent of industrially related PM in the Valley. When the mill shut down for 13
consecutive months in 1986 and 1987 due to a labor dispute,  there was a substantial
reduction of PM levels and a statistically significant decrease  in health-related
measures, including elementary school absences;  hospital admissions for bronchitis
and asthma in preschool-age children; total hospital admissions for pneumonia,
pleurisy, bronchitis, and asthma; pulmonary function abnormalities; and age-adjusted
death rates for malignant and nonmalignant respiratory disease.

      The availability of PM samples collected before and during mill closure and after
its reopening provided a unique opportunity to examine more closely the relationship
between PM exposure and respiratory effects in humans. Prior to  conducting human
exposure studies, Drs. Daniel Costa and Janice Dye of NHEERL's Experimental
Toxicology Division, in collaboration with HSD scientists, studied the effects of Utah
Valley PM on cultured cells and animals  to provide direction in the design of the human
study.

      The human study found that exposure to extracts of PM samples collected
whenever the mill was in operation produced inflammatory changes in the lung similar
to those found in a very mild viral infection.  Exposure to PM extracts taken during mill
closure produced no inflammation.  This  study also suggests that equal amounts of PM
extracts can induce disparate lung  injuries.  Research is continuing to better
understand the specific characteristics of particulate matter that may be eliciting these
adverse health effects.

Ecological Effects Database Available on the Internet

      NHEERL's Mid-Continent Ecology Division (MED) has updated a toxicity
database on the Internet at the EPA ECOTOX(icology) Web site,

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http://www.epa.gov/ecotox  that provides quantitative data on chemical exposures.
This expanded version of the database on ecological effects of chemicals improves
accessibility for the general public, scientists, and risk assessors studying hazardous
pollutants.

      ECOTOX includes independently compiled data sets from MED, the EPA Office
of Pesticide Programs, Russia, and countries belonging to the Organization for
Economic Cooperation and Development. The primary data source, however, is the
open, peer-reviewed literature, with test results identified through comprehensive
searches, manual data abstraction, and entry of relevant data into the database.

      Currently,  ECOTOX includes more than 320,000 individual effect records
abstracted from 17,195 peer-reviewed publications representing more than 7,800
chemicals and 5,300 aquatic and terrestrial species.  The database is updated
quarterly.

      The majority of all papers published on ecotoxicology since 1986 have been
indexed.  The current priority is to cover both aquatic and terrestrial articles in the open
literature from 1989 to the present, although there are some references to papers
published as early as the 1920s. Currently,  ECOTOX includes data only on exposure
to single chemicals, not mixtures.

      ECOTOX has two search modes.  Quick Search allows searches by the most
commonly requested parameters:  major taxonomic classifications, scientific and
common species names, general media classification (terrestrial, aquatic), Chemical
Abstract Services Registry Number, chemical name, observed effect, and publication
year.  Advanced Search uses 10 additional search parameters and allows modifications
in display formats.  Data can be downloaded in either tabular report or ASCII format,
with bibliographic citations provided for all data records.  The complete ECOTOX
database as an ASCII format is available at
http://www.epa.qov/ecotox/help/ecotox download.htm .

      Currently,  ECOTOX data are not evaluated as to the  quality of the test results.
By June 2002 the ECOTOX Web site will be linked to an evaluated terrestrial data set
being developed  at MED with funding from the EPA Office of Solid Waste and
Emergency Response. The linkage will have several advantages.  Risk-based criteria
can be developed for soil contamination of terrestrial  plants and animals at hazardous
waste sites. Various stakeholders will not need to perform repetitious literature
searches and evaluations of toxicity data for the same contaminants at every site, and
more consistency among risk analyses will be attained.

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Field Tests Held on Ocean Response Coastal Analysis System

      Adverse impacts of algal blooms and hypoxia (low dissolved oxygen) in coastal
waters have led to environmental problems such as fish kills, shellfish poisoning, and
beach closures. An early warning system would allow better planning to prevent or
mitigate these environmental impacts.  Imagine accessing a Web site that can give
both real-time information and forecasts of harmful algal  blooms and hypoxia in coastal
waters.  Such an early warning system is being developed through an Interagency
Agreement between NHEERL's Gulf Ecology Division (GED) and the Office of Naval
Research, along with research by the National Oceanographic Partnership Program
and assistance from other federal agencies, universities, and private companies.

      To address environmental issues for the EPA and Navy,  the new Ocean
Response Coastal Analysis System (ORCAS), is being designed to provide real-time,
high-resolution monitoring of multiple biological, physical, chemical, and optical
properties in coastal waters. The system uses an array of sensors called profilers that
are moored to the ocean floor and programmed to float up a guide wire to the surface
while collecting data and transmitting that data to a ship- or shore-based computer.

      For more than two weeks in September, 2001, partner scientists and engineers
visited GED's research facilities in Gulf Breeze, Florida, for the  first field tests of the
ORCAS sensors. Conducted aboard a University of Texas research vessel in
Pensacola Bay and the Gulf of Mexico, the tests covered deployment and recovery of
the sensors, instrument performance, data communication links, data storage, and
visualization systems.  The initial field test was successful and a more comprehensive
field demonstration will be conducted in May 2002 to test the new monitoring system.

Mechanisms Probed for How Dioxin Causes Birth Defects in Mice

      Recent research published in the July, 2001, issue of the journal Toxicological
Sciences provides new insight  into the molecular and cellular mechanisms by which
2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) produces birth defects when administered
to pregnant mice.  Conducted by Dr. Lament Bryant of the School of Public Health at
the University of North Carolina at Chapel Hill and supervised by Dr. Barbara Abbott of
NHEERL's Reproductive Toxicology Division, this was Bryant's  doctoral research
project.

      Earlier work at NHEERL and elsewhere showed that exposure of pregnant
animals to high doses of TCDD, the most toxic of the dioxins, can produce birth defects
in the offspring.  Among these birth defects in mice are cleft palate and hydronephrosis,
a type of kidney damage.  TCDD stimulated overgrowth of epithelial cells of the ureter
(cells lining the inside of the ureter). The overgrowth blocked the flow of urine to the
bladder, resulting in adverse effects on the kidney. An important factor in the

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regulation of epithelial cell growth is Epidermal Growth Factor (EGF), which appears to
have a role in TCDD-induced cleft palate and hydronephrosis.

      Mice that can make EGF are called wild type.  Mice were bred in which the
genetic capability to produce EGF was removed or "knocked out." The cells of these
mice and their offspring therefore cannot produce EGF.  Both wild-type and knock-out
mice were treated with TCDD on a specific day of their pregnancies, and their fetal
offspring were examined for birth defects. In wild-type mice, where EGF is produced
normally, TCDD caused cleft palate.  In the TCDD-treated  knock-out mice, with no EGF
produced, the offspring were resistant to the formation of cleft palate. Although
hydronephrosis occurred in both types of mice, the incidence and severity of this defect
was increased in the EGF knock-out mice.

      These studies show that a cellular factor, EGF, is important in the induction of
cleft palate by TCDD.  Although EGF is not required for the TCDD-induced production
of hydronephrosis, absence of the factor produces an increase of this adverse effect of
TCDD on the fetal urinary tract.

Stream Conditions Assessed by Sampling Biology

      To determine the condition of aquatic ecosystems, the EPA and its partners
need reliable sampling methods that can be applied in a variety of environments. One
important aspect of monitoring and describing what is found in streams is the
"repeatability" of the sampling results, i.e., whether one gets the same kinds and
amounts offish each time the stream is sampled during any one sampling event.
Knowing with accuracy how many and what kinds of fish occur at a site during a
particular time is  essential for assessing biological integrity, patterns of biodiversity,
and the relationships of the fish to the characteristics of their environment.  Scientists at
the Western Ecology Division (WED) developed and validated a statistical model to
quantify the repeatability of sampling methods and published it in the September 2001
issue of Canadian Journal of Fisheries and Aquatic Sciences.

      Related research involved development of a comprehensive assessment of the
stream conditions in the Mid-Atlantic Highlands, an important part of EPA's
Environmental Monitoring and Assessment Program for the Mid-Atlantic states.
Scientists at WED and EPA's National Exposure Research Laboratory developed an
index of stream "health" based on descriptions of the fish communities found. Natural
differences in fish communities were found, as expected, and were related to stream
size, and geographic region in the Mid-Atlantic Highlands.  These natural differences
were used to adjust the index of "health" so that differences due to natural variability
were not confused with differences due to stressors.  The relative importance of
stressors and natural variability as they affect the current distribution of stream fishes in
the Mid-Atlantic Highlands are discussed in the September 2000 issue of the Journal of

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the North American Benthological Society.

Toxicity Studies on Brominated Flame Retardants Under Way

      Scientists at NHEERL's Neurotoxicology and Experimental Toxicology Divisions
are studying the potential health effects of polybrominated diphenyl ethers (PBDEs), a
class of flame retardants used on commercial products such as electronic equipment
and textiles. Although the widespread contamination of ecosystems with these flame
retardants is well known, information on their health effects is sparse.
      Bioaccumulation of PBDEs, due to long-term persistence in body fat, has led to
their detection in humans and wildlife and has become an environmental concern.
Recent non-EPA studies have found increases in concentrations of PBDEs in human
breast milk and in certain fish.

      NHEERL scientists have found that PBDEs are potent endocrine disrupters,
affecting circulating levels of thyroid hormones following short-term exposure in the
juvenile rat. As published in the January 2001  issue of Toxicological Sciences, these
chemicals were found to be active at dosage levels in the 3-10 milligrams per kilogram
per day range.  Current research is focusing on the effects of PBDEs on thyroid
hormones in newborn rats to determine if there are health effects at lower doses of 1
milligram per kilogram per day range. This NHEERL research effort is providing data
needed for risk assessments of PBDEs.

PUBLICATIONS

Proceedings Issued on Risk Assessment Indicators

      The entire 625-page October, 2001,  issue of the International Journal of Human
and Ecological Risk Assessment covers the proceedings from the 5th NHEERL
Symposium, Indicators in Health and Ecological Risk Assessment, held in  Research
Triangle Park, North Carolina, June 2000.  Indicators are measurements used to
determine risk and to establish thresholds for management decisions on health and the
environment. The symposium goals were to substantiate or improve existing indicators
and to integrate human health and ecological issues.

      Dr.  William Fisher of NHEERL's Gulf Ecology Division (GED) chaired the
symposium and  served as guest editor of the proceedings. The following list,  by name,
division, and session title, shows other NHEERL scientists who served as session
chairs and editors:  Dr. Ralph Cooper, Reproductive Toxicology Division, endocrine
disrupting chemicals; Dr. William Mundy and Dr. Stan Barone, Jr.,  Neurotoxicology
Division (NTD), persistent bioaccumulating toxicants; Dr. Michael Madden, Human

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Studies Division, ambient ozone; Dr. Henry Walker, Atlantic Ecology Division (AED),
global atmospheric change; Drs. Richard Greene, GED, and Kenneth Hudnell, NTD,
harmful algal blooms; and Dr. John Paul, AED, coastal communities.

      Like the symposium, the proceedings attempt to reconcile the sometimes
conflicting views of scientists, risk assessors, and resource and public health
managers. Articles by 41 national and international experts examine the development
and application of health and ecological indicators for risk in the areas covered in the
six sessions. Throughout, the articles address indicator measurements, assessment
questions and endpoints, and social values. The results support the role of NHEERL
and ORD in promoting sound science in risk assessment.

Booklet on Ecological History of New Bedford Harbor Published

      A recent 32-page booklet "Imprint of the Past: Ecological History of New Bedford
Harbor"(U.S. EPA, Region 1; 2001; No. 901-R-01-003), has been produced by
NHEERL's Atlantic Ecology Division, the New Bedford Whaling Museum in
Massachusetts and EPA Region 1  Office in Boston for the general public and
teachers.  It is available at http://www.epa.gov/nbh, the new public Web site.

      In addition to describing New Bedford Harbor's ecological history, the booklet
includes a general section on environmental contaminants, a glossary,  maps and
figures, a listing of relevant organizations in New Bedford, and old photographs, prints,
and paintings from the New Bedford Whaling Museum.

      Ecological history, the study of the interaction between humans and their
environment, is especially relevant in New Bedford Harbor, Massachusetts. Although
New Bedford Harbor gained notoriety in 1982 when it was named a  Superfund site
because of its PCB contamination in sediments, the current environmental conditions
are the result of more than 250 years of agricultural, commercial, and industrial activity.

      The development of ecological histories is relevant to EPA because they are
useful tools in community-based environmental protection and they  promote the
involvement of the local citizens. They also provide managers with  realistic goals for
remediation or restoration, give  scientists a more complete understanding of current
conditions, and educate business leaders and citizens.

      Other products from this study include two journal articles:  "Historical Analysis,
A Valuable Tool in Community-based Environmental Protection" in the May 2001 issue
of Marine Pollution Bulletin uses New Bedford Harbor as a case study to explain the
value of ecological histories to managers and scientists.  "A Story of Urbanization and
Ecological Connections" in the July 2000 issue of Environmental History documents the
New Bedford story for environmental historians.

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Proceedings Issued on Microbes and Disinfection By-products in Drinking Water

      Although chlorine has long been the standard treatment for removing microbial
contamination from public drinking water supplies, there is growing concern about
balancing the need to remove microorganisms from water by disinfection and the
toxicity of certain disinfection by-products (DBFs). What other methods of disinfection
are available? What are their relative risks, benefits, and costs? Do developed and
developing countries have the same concerns?  Eight NHEERL scientists are among
the contributors to a 656-page proceedings from an international conference that
addresses these and other questions. Dr. Fred Hauchman served as a contributor and
editor.  NHEERL was also one of 11 co-sponsors of the conference and publication.

      The published proceedings entitled "Microbial Pathogens and Disinfection By-
products in Drinking Water:  Health Effects and Management of Risks" are from the
Second International Conference on the Safety of Water Disinfection: Balancing
Chemical and Microbial Risks, held in Miami Beach, Florida, Nov.  15-17, 1999.  Almost
200 scientists, drinking water investigators, and regulators from 31 countries attended
the conference.

      Key features of both the conference and the proceedings were interdisciplinary
participation, a global scope of both the presentations and participants, evaluation  of
needs and priorities in developed versus developing countries, and the effects of
regional and geographic differences on decision-making related to ensuring the safety
of drinking water supplies.

      Increases in population size and associated stresses continue to limit the
availability of clean water in many areas of the world. The proceedings provide a
current picture of the available information related to water disinfections and indicates
the direction of future priorities.  The paperback publication, ISBN  1-57881-117-1,
issued August 21, 2001,  is available from ILSI Press, Washington, DC.

New England Climate Change Report Published

       Dr. Henry Walker at NHEERL's Atlantic Ecology Division co-authored two
chapters of an 88-page report on Preparing for a Changing Climate. The Potential
Consequences of Climate Variability and Change: New England Overview,  published in
September by the University of New Hampshire.

      Global warming during the 20th century is shown to be associated with
significant environmental changes in New England, including milder winters, reduced
snowfall, earlier ice-thawing in lakes during the spring, earlier maple-sap flow, and a
decrease in selected fish populations.  Over the past 100 years, there has been a
long-term trend in decreased maple sap and syrup production  in New England and, in

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the last 30 years, a major increase in their production in Canada.  Winter flounder, a
major, commercially important flatfish, breeds and lays eggs on the bottom in cold,
shallow estuarine waters in mid-winter when predation rates are low.  Between 1960
and 1990, when the winter water temperature of Narragansett Bay increased by almost
5 degrees Fahrenheit, the abundance of flounder declined rapidly.

      Two climate prediction models used in this study were based on a scenario of
global atmospheric carbon dioxide levels increasing at a rate of about one percent of
1990 levels per year over the next century. As a result, the models projected a 6 to 10
degree Fahrenheit increase in New England's temperatures by 2100.  That high of an
increase could result in the climate of Boston becoming more like that of Richmond,
Virginia, or Atlanta, Georgia. Under the simulated 2100 climate, the dominant New
England forest cover eventually could change from spruce/fir and maple/beech/birch to
one of oak/pine/hickory. There could also be a 50-100 percent loss of habitat
favorable for brown, brook, and rainbow trout,  cold freshwater fish highly valued for
sport fishing.  Continued warming of saltwater could also reduce the food  supply to
bottom-dwelling species, with adverse impacts on important commercial fisheries.

      Funding for this New England  Regional Assessment (NERA) was provided by
the National Science Foundation as part of the U.S. Global Change Research
Program. A direct link to the report is at http://www.necci.sr.unh.edu/2001-NERA-
report.html .  Paper copies are available by contacting the University of New
Hampshire at 603-862-1792.

                      MEETINGS / CONFERENCES

International Symposium on Polycyclic Aromatic Compounds Held

      Polycyclic aromatic compounds (PACs) are among the oldest known human
carcinogens, and because of their human and ecological exposure, pervasiveness,
and abundance, this class of compounds has been widely studied. NHEERL and
EPA's Office of Solid Waste and Emergency Response were two of 10 co-sponsors of
the 18th International Symposium on Polycyclic Aromatic Compounds,  held Sept. 9-13,
2001, at the University of Cincinnati.  Drs. Stephen Nesnow and Jeffrey Ross of the
NHEERL Environmental Carcinogenesis Division (ECD) co-chaired the program
committee and, with Dr. James Rabinowitz of ECD, also chaired scientific sessions.

      The 177 attendees from 14 nations focused on recent scientific developments in
the chemistry and biology of PACs and related compounds and identified  important
advances, areas for research, and themes for multi-disciplinary collaboration. Session
topics included the molecular biology of PAC carcinogenesis; human and
environmental exposure; chemical analysis and synthesis; environmental  aspects such
as biodegradation, bioremediation, and ecotoxicology; and risk assessment.


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      The symposium also included six short courses on the chemistry and detection
of PACs and metabolites in environmental and biological samples, and the biology and
molecular epidemiology of PACs, as well as exhibits from suppliers and manufacturers.
The proceedings will be published in the journal Polycylic Aromatic Compounds in
2002.

International Breast Cancer Meeting Held

      An international meeting on the environmental factors associated with breast
cancer was held Sept. 22-25, 2001, in Research Triangle Park (RTP), North Carolina.
Co-sponsors were NHEERL, National Institute of Environmental Health Sciences,
National Cancer Institute, Genentech, and the local chapter of the Environmental
Mutagen Society (EMS), the Genotoxicity and Environmental Mutagen Society.

       Dr. David DeMarini of NHEERL's Environmental Carcinogenesis Division and
president of EMS, chaired the meeting.  More than 100 scientists, physicians, and
students attended to hear 27 invited speakers from around the world. Only five
speakers and eight pre-registered attendees were unable to come to RTP because of
the events of September 11.

      There were sessions on the epidemiology of breast cancer; general trends from
animal studies; environmental mutagens/carcinogens, including carcinogens in food,
tobacco, and industrial sources as potential causes of the cancer; and the mechanisms
of breast cancer formation.  Workshops were conducted by breast cancer survivors
and by members of the National Breast Cancer Coalition, a group active in prevention
and support activities.

      Concluding sessions covered the genetics of breast cancer and promising new
treatments for this disease.  Taxol, one of the main drugs used to treat breast cancer,
was discovered by Drs. Monroe Wall and M.C. Wani of the Research Triangle
Institute, Research Triangle Park, North Carolina.  Wani concluded the meeting with
an overview of their discovery and development of this drug.
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