SCIENCE REPORT
RESEARCH AND DEVELOPMENT
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NATIONAL HEALTH AND
ENVIRONMENTAL
RESEARCH LABORATORY
VOLUME 3, ISSUE 1
SPRING aoO3
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CONTENTS
Click on title to link directly to article.
RESEARCH
Particles from World Trade Center Collapse Cause Respiratory Toxicitv in Mice 3
Exposure Risk Assessment Models Evaluated 4
Reactive Oxygen Species Implicated in DMA Damage Caused by Arsenicals 5
Confocal Microscopy Gives Enhanced 3-D Images of Biological Structures 6
Model Forecasts Atrazine and PCB Concentrations in Lake Michigan 7
PUBLICATIONS
Accounting for Organic Carbon Held in Forest Soils in the U.S. and Puerto Rico 10
Proceedings on "Coastal Monitoring Through Partnerships" Published 11
AWARDS
GED Scientist Honored with SETAC Government Service Award 12
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RESEARCH
Particles from World Trade Center Collapse Cause Respiratory Toxicity in Mice
The September 11, 2001 terrorist attack on New York City's World Trade Center
(WTC) caused an unprecedented environmental emergency. The collapse of the towers
sent a tremendous cloud of crushed building materials and other pollutants into the air of
lower Manhattan. Analysis of fallen dust samples collected in the first few days after the
attack showed that 1 - 4% by weight consisted of particles small enough to be respirable.
These particles included fine particulate matter, or PM25 (PM less than 2.5 jim in
diameter), which can be inhaled deep into the lungs and is associated with
cardiovascular and respiratory health effects. Given the extremely high concentrations
of dust immediately after the fall of the towers, even a relatively small proportion of PM25
could have contributed to breathing problems in rescue workers and others who were not
wearing protective masks.
In two papers recently accepted by Environmental Health Perspectives for
publication in June 2003, scientists from the U.S. EPA, New York University, and
Michigan State University examined the chemical properties of the PM25 fraction of the
dust derived from the destruction of the WTC and its toxicity in the respiratory tract of
mice.
Samples of WTC PM25 isolated from fallen dust collected 1 or 2 days after the
disaster were composed of calcium-based compounds found in building materials.
Assessment of short-term effects in mice 1 to 3 days after exposure showed that these
samples caused mild to moderate degrees of lung inflammation when administered at a
relatively high dose of 100 ug directly into the airways. The inflammation, however, was
less than that caused by a toxic PM emission source (residual oil fly ash, ROFA) or a
standard ambient air PM sample (NIST 1649a). Most importantly, this dose of WTC
PM25 caused airway hyper-responsiveness comparable to that from NIST 1649a and
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greater than that from the toxic ROFA sample. The hyper-responsiveness indicates that
the high dose group was primed to react to triggering agents that can constrict the
airways. Lower doses of 10 and 32 jig administered directly into the airways, or the
inhalation of 11 mg/m3 in air (estimated to deposit approximately 14 ug of PM25 in the
respiratory tract), did not induce significant inflammation or hyper-responsiveness.
Although the concentrations of PM2 5 immediately following the WTC collapse are
unknown, it was estimated that healthy people exposed to about 425 ug/m3 of WTC
PM25 in air for 8 hours would get a dose comparable to the high dose in the mice. The
authors concluded that inhalation of high doses of WTC PM25 derived from building
materials could contribute to the development of pulmonary inflammation, airway hyper-
responsiveness, and cough. Most people, however, would not be expected to
experience adverse short-term respiratory effects from exposure to even moderately
high WTC PM25 levels (estimated at 130 |ig/m3 for 8 hours). The persistence of any
effects of inhaled WTC PM25 is unknown and was not addressed in these studies.
These studies provide essential information on the chemistry and respiratory toxicity of
WTC PM25, which is a necessary component in the evaluation of health risks from the
WTC disaster.
Although these research articles are not yet available in print, they are available
online at http://ehp.niehs.nih.ciov/docs/admin/newest.htmW11 17. A full EPA report is
available at http://www.epa.gov/nheerl/wtc/WTC report 7b3i.pdf.
Exposure Risk Assessment Models Evaluated
In assessing human non-cancer risks from exposures to toxicants, EPA must
judge which type of short-term acute exposure is most likely to lead to long-term,
chronic, irreversible effects in the lungs. Five Experimental Toxicology Division
scientists-Dr. Gary Hatch, Dr. Urmila Kodavanti, Dr. Dan Costa, Kay Crissman, and
Ralph Slade-examined factors important in the progression from acute lung injury to
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chronic formation of scar tissue (fibrosis). Rats were exposed to phosgene, a toxic
industrial gas, under different conditions of time and exposure concentration, and both
acute and chronic indicators of effect were measured. The results suggest that sharp
peaks of exposure separated by long intervals induce more severe, chronic injury than
continuous, low-level exposures.
Traditionally, EPA has judged the potential for chronic effects of air pollutants by
using a mathematical calculation of exposure dose. The pollutant concentration is
multiplied by the time of exposure to estimate the total dose of the toxic agent. This
"concentration-time model" makes long-term, low-concentration exposures appear the
same as short-term, high-concentration exposures, but it appears that the model may
underestimate effects that occur during episodic exposures to phosgene and other air
toxics with similar reactivity. Persistent lung injury to rodents was highest after a series
of intermittent spikes of exposure. Longer times between exposure appeared to allow
adaptation to disappear, causing greater injury with each subsequent exposure spike
and, ultimately, greater chronic injury. A conceptual model was developed to relate
acute injury, adaptation, and chronic lung injury. [Toxicology and Industrial Health,
1/(Issue 5-10):285-293].
Reactive Oxygen Species Implicated in DMA Damage Caused by Arsenicals
Recent research in the Environmental Carcinogenesis Division (ECD) further
explains the mode of action of two genotoxic arsenic compounds. The genotoxic effect
of arsenic arises from reactive oxygen species (ROS) generated from two methylated
trivalent forms of inorganic arsenic, MMA"' and DMA'". These findings may eventually
lead to revision of the extrapolation model currently used to estimate human cancer risk
from arsenic exposure.
In 2001 EPA proposed a lower Maximum Contaminant Level (MCL) of 10 ug/L for
arsenic, based on published research on arsenic-exposed populations in Taiwan, China,
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but without knowing the actual mode of action for arsenic. Given the new information
from ECD, the shape of the arsenic dose-response curve may differ from that used in the
original model.
Naturally occurring inorganic arsenic exists in drinking water in two major forms:
arsenite and arsenate. In mammals, inorganic arsenic is biotransformed by methylation
into a number of organometallic forms of arsenic, which have been found in the urine of
humans and rodents exposed to arsenic in their drinking water. Two of these forms are
MMA1" and DMA1", both of which had been previously shown by NHEERL researchers to
damage the DMA of mammalian cells in culture. The current research uncovered the
genotoxic mode of action of these arsenicals.
ROS are identified as arsenic-derived intermediates in the DMA damage process.
Research by Dr. Stephen Nesnow, the late Dr. Marc Mass, Barbara Roop, and Guy
Lambert (all of ECD), with colleagues from the National Institute of Environmental Health
Sciences and the University of British Columbia, found that four ROS inhibitors, including
the hormone melatonin and an antioxidant analog of Vitamin E, were extremely effective
in preventing the DMA-damaging effects of both arsenicals.
The researchers used a special spectroscopic technique to identify the hydroxyl
radical as the ROS form responsible for the DMA damage. The ROS are generated
during the process of air oxidation of the trivalent arsenicals to their pentavalent forms.
The ECD researchers concluded that methylated trivalent forms of consumed inorganic
arsenic damage DMA through the formation of ROS. [Chemical Research in Toxicology,
2002, 15:1627-1634].
Confocal Microscopy Gives Enhanced 3-D Images of Biological Structures
Confocal microscopy, an important technique used to visualize biological
structures in three dimensions, is the foundation of many toxicological assays. A recent
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paper by Dr. Robert Zucker of the Reproductive Toxicology Division evaluates the
performance of the confocal laser-scanning microscope (CLSM) used in a wide variety of
projects, including the effects of methoxychlor on rat pituitary and ovary, atrazine on rat
prostate development, and ethanol administration to pregnant mice on the development
of areas of the brain in the offspring.
CLSM data consists of digital images that are similar to photographs, and these
images can be obtained even if the equipment is performing sub-optimally. CLSM data
are most reliable, however, when the instrument is correctly aligned and the laser power
is stable. This paper describes the equipment needed for performance testing, which
includes a photomultiplier detector to measure fluorescent light emission, a custom-
made detector holder built in the NHEERL machine shop to fit onto the microscope, and
an inexpensive, portable power meter to measure the amount of emitted light. A power
output test can determine whether the system is misaligned, functioning badly, or if the
laser needs to be replaced. The paper includes a reference table that compares
maximum power output using different types of equipment and lasers. The table will be
especially valuable in assessing the performance of CLSM systems used in other
laboratories. This new technique for optimizing confocal microscope performance is now
available to the broader scientific research community. It will improve the accuracy and
reliability of data collected, which are important factors for data gathered for regulatory
decision making. [Microscopy Today, 2002, 10(6):20-22].
Model Forecasts Atrazine and PCB Concentrations in Lake Michigan
To assist managers in remedial and regulatory decision-making, a multimedia
mathematical modeling framework was applied to Lake Michigan, the sixth largest lake in
the world. The Mid-Continent Ecology Division (MED), cooperating with EPA Region 5;
the EPA Great Lakes National Program Office; the states of Michigan, Wisconsin, Illinois,
and Indiana; the First Nations (Native American tribes); and other federal, public, and
private groups, completed the 2002 Lake Michigan Lakewide Management Plan (LaMP).
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MED used mass balances of atrazine and PCBs to predict several concentrations of
these pollutants under different remedial or regulatory scenarios for setting priorities with
lakewide and local watershed perspectives. The LaMP for each of the five Great Lakes
is updated every two years. It summarizes the current status of the lake, tracks
significant activities and new initiatives, and describes improvements in habitat, cleanup,
indicators, and contaminants.
The mass balance shows that approximately 70% of the atrazine loading is from
tributaries and 30% from atmospheric wet deposition. The greatest tributary loads
originate from the St. Joseph, Grand, and Fox Rivers. Forecasts indicate that atrazine
concentrations will increase from 40 to 70 ng/L over the next 150-200 years at present
loadings. A 57% reduction in tributary loading would be required to maintain the 40 ng/L
concentration under the "no further degradation" clause of the U.S./Canada Water
Quality Agreement and the Clean Water Act. Present and forecasted lakewide atrazine
concentrations fall below U.S. EPA thresholds for fish (20,000 ng/L), invertebrates
(10,000 ng/L), non-vascular plants (2,300 ng/L), and vascular plants (2,300 ng/L) in
freshwater lakes and reservoirs. Additional information is available at the following Web
site: http://www.epa.gov/oppsrrd1/reregistration/atrazine .
In contrast, PCB concentrations in Lake Michigan are dominated first by dynamic
interactions and processes of sediments with the water column, then by substantial
inputs from the atmosphere, and finally by contributions from tributaries. The largest
tributary contributors are the Fox, Grand Calumet, and Kalamazoo Rivers. Model
forecasts indicate that even with no further remedial action, PCB concentrations in lake
trout will continue to decrease, but that the rate of decrease could be accelerated by
further reductions in atmospheric deposition and tributary inputs. As PCBs are depleted
from sediments by resuspension from sediments to water, volatilization into the
atmosphere, and losses to deep burial in sediments, the PCB atmospheric vapor
concentration (global background) will drive the system. Forecasts indicate that a 50%
reduction in atmospheric and tributary loads would further decrease PCB concentrations
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in lake trout and move closer to achieving the target level of 0.05 ppm for the unlimited
consumption of fish by humans. See the following Web site for additional information:
http://www.michig.an.qov/mesb/0,1607,7-117-1254-28636-.OO.html .
The 100-page LaMP for Lake Michigan is available at the following Web site:
http://www.epa.gov/glnpo/lakemich/lm02/index.html .
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PUBLICATIONS
Accounting for Organic Carbon Held in Forest Soils in the U.S. and Puerto Rico
Because of intense concern that increasing levels of atmospheric carbon dioxide
may be causing global climate change, identifying ecosystems that can sequester and
store carbon is a high priority. Scientists in the Western Ecology Division (WED) have
completed an inventory of the organic carbon currently held in forest soils in the United
States and Puerto Rico. Organic carbon in soils is derived from the photosynthetic
fixation of atmospheric carbon dioxide that enters the soil through plant roots or plant
litter (leaves, branches, etc.) deposited in or on the soil surface. Soils are the largest
terrestrial reservoir of carbon (approximately three times that held in global vegetation
and twice that held in the atmosphere).
In Chapter 4 of The Potential of U.S. Forest Soils to Sequester Carbon and
Mitigate the Greenhouse Effect, a book edited by J.M. Kimble et al. and published by
CRC Press in 2002, Dr. Mark G. Johnson of WED and Jeffrey Kern of Dynamac
Corporation use the inventory as a baseline for monitoring future changes in the amount
of soil carbon held in forested systems and for identifying those forest types that may be
managed to sequester additional carbon below ground.
To create a map of soil carbon for the contiguous U.S. and Puerto Rico, the
researchers determined spatial patterns and total soil organic carbon in forests by using
digital soil survey data linked to a large national soil-characterization database. They
then combined the resultant soil organic carbon maps with existing maps of forest types
to create new maps showing the geographical distribution of carbon in forest soils.
Tables list the amounts of soil organic carbon at three depths in various types of forests
and distinguish between the contribution of organic soils and mineral soils to total soil
carbon. In forested areas of the United States and Puerto Rico, Johnson and Kern
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estimate that the amount of carbon held in the upper 100 centimeters of soil to be 35.5
petagrams of carbon (one petagram is equal to 1015 grams or 1000 million metric tons).
Proceedings for "Coastal Monitoring Through Partnerships" Published
The proceedings for EMAP 2001, "Coastal Monitoring Through Partnerships," a
symposium of the EPA Environmental Monitoring and Assessment Program (EMAP)
held in Pensacola, Florida, have been published recently in both journal and book
format. The publications contain 33 peer-reviewed papers describing multidisciplinary
coastal and estuarine environmental monitoring programs designed and implemented by
EPA in partnership with federal and state agencies, academia, Native American tribes,
and non-governmental organizations. The international journal, Environmental
Monitoring and Assessment, devoted the entire January 2003 special issue (Volume 81,
lssue1-3) to the proceedings. Journal subscribers can access the full papers online at
the following URL: http://www.kluweronline.com/issn/0167-6369 . Non-subscribers have
free access to the abstracts at the same URL. A hard-cover book version (ISBN 1-4020-
1089-3, 420 pages), is also available.
Throughout, the papers emphasize how successful partnerships were used to
identify, diagnose, and solve coastal environmental problems and how research and
technology transfer have led to more efficient, less expensive, and more scientifically
rigorous monitoring and assessment programs.
Three NHEERL scientists (Dr. Brian Melzian of the Atlantic Ecology Division,
Virginia Engle of the Gulf Ecology Division, and Dr. Shabeg Sandhu of EMAP) and
Malissa McAlister of the Council of State Governments served as scientific editors.
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AWARDS
GED Scientist Honored with SETAC Government Service Award
Dr. Foster "Sonny" Mayer of the Gulf Ecology Division (GED) received the 2002
Society of Environmental Toxicology and Chemistry Government Service Award at the
society's annual meeting in Salt Lake City, Utah, November 16-20, 2002. The award
recognizes exemplary dedication and service in promoting the application of environ-
mental toxicology and chemistry to risk assessment in a government function; fostering
programs that aid in the development of ecologically sound and acceptable practices and
principles; and providing a forum for communication. Dr. Mayer was recognized for
service in all three areas during his long career, first with the U.S. Fish and Wildlife
Service (1970-84) and then with EPA (1985-present).
Dr. Mayer's contributions have ranged from the first two workshops on ecological
risk assessment in the late 1970s to his recent development of probability-based risk
assessment techniques used in evaluating national water quality criteria for the
protection of endangered species. Other career highlights include serving as U.S.
Science Advisor in the US-USSR Scientific Exchange; promoting multidisciplinary
research in toxicology and risk assessment on a watershed basis; helping create of
SETAC in 1979; and publishing 126 journal articles, reports, books, and book chapters.
He also had appointments at five universities, where he was research advisor or
committee member for 16 master's and 10 doctoral candidates.
SETAC membership is drawn from government, universities, business, and
public-interest groups from more than 70 countries. More than 5,000 individual members
have technical specialities in chemistry, toxicology, ecology, atmospheric health, earth
sciences, and environmental engineering; and Dr. Mayer's eclectic background
overlapped many of them.
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