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In Vivo Relative
Oral Bioavailability of Arsenic from CCA-Affected Soils in
the Primate
Dr.
Stephen M. Roberts, University of Florida, Gainesville, FL
Raymond
J. Bergeron, University of Florida, Gainesville, FL
USEPA
SHEDS Model: Methodology for Exposure Assessment for Wood
Preservatives
Haluk Özkaynak, U.S.
EPA, Office of Research and Development, Washington, DC
Valerie Zartarian, U.S. EPA, Office of Research and Development,
Research Triangle Park, NC
Jianping Xue, U.S. EPA, Office of Research and
Development, Research Triangle Park, NC
Winston Dang, U.S.EPA,
Office of Pesticide Programs, Washington, DC
Exposure
and Risk Assessment for Arsenic from CCA-Treated Wood
Playground Structures
Dr.
Kristina Hatlelid, U.S. Consumer Product Safety
Commission, Washington, DC
David Cobb, U.S. Consumer Product Safety Commission,
Washington, DC
Dwayne Davis, U.S. Consumer Product Safety Commission,
Washington, DC
Mark S. Levenson, U.S. Consumer Product Safety Commission,
Washington, DC
Jonathan D. Midgett, U.S. Consumer Product Safety
Commission, Washington, DC
Treye A. Thomas, U.S. Consumer Product Safety Commission,
Washington, DC
Patricia M. Bittner, U.S. Consumer Product Safety
Commission, Washington, DC
Comparison
of a Probabilistic/Mechanistic (SHEDS) Approach to a
Deterministic/Empirical Approach for Evaluating Exposures
to CCA-Treated
Wood
Dr.
Barbara D. Beck, Gradient Corporation, Cambridge, MA
Catherine
Petito Boyce, Gradient Corporation, Seattle, WA
Eric M. Dube, Gradient Corporation, Cambridge, MA
Background
Inorganic Arsenic Exposures in Children
Dr. Joyce S. Tsuji, Exponent®,
Bellevue, WA
Relationship
Between Childhood Arsenic Exposures and Cancer Risks in
the U.S. and Findings of an Ecological Arsenic Health
Effects Study
Floyd Frost, Ph.D., Lovelace Respiratory Research
Institute, Albuquerque, NM
Kristine Tollestrup, Ph.D, University of New Mexico, Dept.
of Family Medicine
Lucy Harter, Washington State Dept. of Health
Melissa Roberts, Lovelace Respiratory Research Institute,
Albuquerque, NM
Arsenic
Epidemiology & Cancer Slope Factor
Dr. Steven H. Lamm, Consultants in Epidemiology and
Occupational Health, Inc., Washington, D.C.
In
Vivo
Relative Oral Bioavailability of Arsenic from CCA-Affected
Soils in the Primate
Stephen
M. Roberts, Center for Environmental & Human
Toxicology, University of Florida, Box 110885,
Gainesville, FL 32611, Tel: 352 392-4700 ext. 5500, Fax:
352 392-4707
Raymond J. Bergeron, Department of Medicinal Chemistry,
University of Florida, Box 100485, Gainesville, FL 32610,
Tel: 325 846-1956
The
relative oral bioavailability of arsenic in soil from a
former CCA wood treatment facility was measured in the
Cebus monkey. In preliminary experiments, sodium arsenate in solution was
administered intravenously and orally to five male Cebus
monkeys, and blood, urine, and feces were collected.
The disappearance of arsenic from blood following
an intravenous dose in the monkeys was similar to that
reported previously in humans.
Further, the fraction of dose excreted in urine and
feces after both intravenous and oral administration were
comparable to values reported in humans.
Relative bioavailability of arsenic from soil was
measured by comparing arsenic excretion following a single
oral dose of soil with arsenic excretion following a
similar oral arsenic dose as sodium arsenate in water.
The relative bioavailability of arsenic from the
soil sample was found to be 16.3 ± 6.5 % (mean ± SD) in
five monkeys. This
research was supported through a contract with the Florida
Department of Environmental Protection.
USEPA
SHEDS Model: Methodology for Exposure Assessment for Wood
Preservatives
Haluk
Özkaynak, U.S.
EPA, Office of Research and Development, Ariel Rios
Building, 1200 Pennsylvania Avenue, NW, MC-8601 D (room
400W22), Washington, DC 20460, Tel: 202-564-1531, Fax:
202-565-0075
Valerie Zartarian, U.S. EPA, Office of Research and
Development, 109 TW Alexander Drive, Mail Drop E205-02,
Research Triangle Park, NC 27711, Tel: 617-918-1541, Fax:
617-918-0541
Jianping Xue, U.S. EPA, Office of Research and
Development, 109 TW Alexander Drive, Mail Drop E205-02,
Research Triangle Park, NC 27711, Tel: 919-541-7962, Fax:
919-541-9444
Winston Dang, U.S.EPA, Office of Pesticide Programs,
Office of Prevention, Pesticides and Toxic Substances,
MC-7510C, 1200 Pennsylvania Avenue, N.W., Washington, DC
20460-0001, Tel: 703-308-6216 Fax: 703-308-6466
A
physically-based, Monte Carlo probabilistic model
(SHEDS-Wood: Stochastic Human Exposure
and Dose Simulation model for wood
preservatives) has been applied to assess the exposure and
dose of children to arsenic (As) and chromium (Cr) from
contact with chromated copper arsenate (CCA)-treated
playsets and residential decks.
Short-term
(for As and Cr), intermediate-term (for As and Cr), and
lifetime (for As only) absorbed doses are estimated for:
dermal contact with playset or deck residues; dermal
contact with soil concentrations around treated playsets
or decks; ingestion of CCA-containing soil near treated
playsets or decks; and ingestion of wood residues via the
hand-to-mouth pathway.
SHEDS-Wood
calculates the predicted exposure and dose to As and Cr
using age and gender representative time-location-activity
diaries from EPA’s Consolidated Human Activity Database
(CHAD). Based on user-specified inputs, exposure days and
exposure events within a day are simulated.
The time series of exposure and dose are computed
using pathway-specific exposure equations and the
real-time diary activities for which a contact event is
possible. Model
inputs, represented as analytical distributions (e.g.,
lognormal, beta) include: fraction of outdoor time and
days per year a child plays on/around playsets and decks;
As and Cr residue and soil concentrations on or near CCA
treated playsets or decks; and various exposure factors
such as residue-to-skin transfer efficiencies,
soil-to-skin adherence factor, saliva and bathing removal
efficiency, daily incidental soil ingestion rate, fraction
of hand skin surface area contacting soil, frequency of
hand to mouth activity, maximum dermal loading, and dermal
and GI absorption rates.
Model results for the simulated population are
analyzed to determine the dominant pathways influencing
predicted exposures and dose. Both deterministic and
statistical methods are used to assess the sensitivity of
results to key input variables. Uncertainty analyses are
performed using the 2nd Stage Monte-Carlo
simulation results and a nonparametric bootstrap
methodology.
Disclaimer: This work has been funded wholly by the United
States Environmental Protection Agency.
It has been subjected to Agency review and approved
for publication.
Exposure
and Risk Assessment for Arsenic from CCA-Treated Wood
Playground Structures
Kristina
M. Hatlelid, Consumer Product Safety Commission,
Washington, D.C. 20207, Tel: 301-504-7254, Fax:
301-504-0079
David Cobb, U.S. Consumer Product Safety Commission,
Washington, D.C. 20207, Tel: 301-424-6421 x106, Fax:
301-413-0000
Dwayne Davis, U.S. Consumer Product Safety Commission,
Washington, D.C. 20207, Tel: 301-424-6421 x107, Fax:
301-413-0000
Mark S. Levenson, U.S. Consumer Product Safety Commission,
Washington, D.C. 20207, Tel: 301-504-7408, Fax:
301-504-0081
Jonathan D. Midgett, U.S. Consumer Product Safety
Commission, Washington, D.C. 20207, Tel:
301-504-7692, Fax: 301-504-0124
Treye A. Thomas, U.S. Consumer Product Safety Commission,
Washington, D.C. 20207, Tel:
301-504-7738, Fax: 301-504-0079
Patricia M. Bittner, U.S. Consumer Product Safety
Commission, Washington, D.C. 20207, Tel:
301-504-7263, Fax: 301-504-0079
In
June, 2001, the U.S. Consumer Product Safety Commission (CPSC)
docketed a petition from the Environmental Working Group
and the Healthy Building Network that requested that the
Commission enact an immediate ban of chromated copper
arsenate (CCA)-treated wood for use in playground
equipment.
CPSC
staff completed toxicological reviews of CCA components,
chromium, copper, and arsenic, but chose to focus on
arsenic because it is the most potent of the three
chemicals. The staff considers that the principal exposure
to arsenic from CCA-treated wood occurs through transfer
of wood surface arsenic residues to a child’s hands and
fingers and subsequent direct (e.g.,
thumb-sucking) and indirect (e.g.,
handling of toys or food) hand-to-mouth transfer of the
residues.
CPSC
staff conducted laboratory and field studies to estimate
the amount of arsenic to which a child might be exposed
during a typical playtime on CCA-treated wood playsets.
The staff measured the dislodgeable arsenic levels on the
surface of CCA-treated wood structures in the Washington,
D.C. metropolitan area using 8 CCA-treated wood decks and
12 CCA-treated wood playsets, representing a variety of
ages, wood treatments, and manufacturers. The study used
adult volunteers using their bare hands, as well as
surrogate materials, e.g., polyester cloth, that could be
used in place of the bare hands, to rub the surface of the
wood structures.
Based
on the field studies, the staff estimated that the mean
dislodgeable arsenic levels from handling CCA-treated wood
playground equipment is about 7.6 micrograms. Using this
information and other assumptions in a deterministic risk
assessment model, the CPSC staff concluded that a young
child who plays primarily on CCA-treated wood playground
structures in early childhood has an increased lifetime
risk of 2 to 100 per million of developing lung or bladder
cancer. This is an increased risk above the risk of cancer
due to other factors during one’s lifetime. (The
opinions expressed by the authors do not necessarily
represent the views of the Commission.
As this abstract was prepared by the authors in
their official capacity, this abstract is in the public
domain and may be freely copied or reprinted.)
Comparison
of a Probabilistic/Mechanistic (SHEDS) Approach to a
Deterministic/Empirical Approach for Evaluating Exposures
to CCA-Treated
Wood
Barbara
D. Beck,
Gradient Corporation, Cambridge, MA
Catherine Petito Boyce, Gradient Corporation, Seattle, WA
Eric M. Dube, Gradient Corporation, Cambridge, MA
Quantifying
potential exposures and risks to inorganic arsenic (Asi)
releases from wood treated with chromated copper arsenate
(CCA) presents several risk assessment challenges.
For example, standardized algorithms are not
available in typical risk assessment guidance for
quantifying transfer of dislodgeable arsenic from wood
surfaces into the body.
Consequently, scenario-specific assumptions for
certain exposure parameters are
being refined, e.g., by conducting relevant
scientific studies. This
presentation compares two methodologies
for conducting human health risk assessments (HHRAs)
for Asi from treated wood: (1) a probabilistic,
mechanistic methodology as exemplified by the U.S.
Environmental Protection Agency’s Stochastic Human
Exposure and Dose Simulation model as applied to a wood
preservative exposure scenario (SHEDS-Wood) and (2) a
deterministic, empirical methodology with a focused
sensitivity analysis (DEM/FS), as exemplified by recent
HHRA’s conducted by the U.S. Consumer Product Safety
Commission (CPSC) and Gradient Corporation.
Strengths and limitations of each model are
described, and data needs are highlighted for each
approach. Among
other observations, the SHEDS-Wood approach allows
specific activity patterns to be incorporated in the model
and more explicitly characterizes variability and
uncertainty in the model results.
By contrast, the lack of available data for many of
the necessary input assumptions and for validating the
model results adds uncertainty when interpreting estimates
derived using the SHEDS-Wood model.
The DEM/FS approach relies on an empirical approach
based on soil ingestion studies to estimate intake of
surface residues from CCA-treated wood, an approach which
provides a benchmark for evaluating the validity of
estimates for this pathway.
The focused sensitivity analysis component of the
DEM/FS approach allows analysts to readily identify
critical assumptions and to assess the conservatism of the
analyses. The
DEM/FS approach cannot directly incorporate information
regarding certain behavioral variables, however, such as
variations in numbers of hand-to-mouth contacts, and does
not provide quantitative information regarding the
distribution of potential risk levels.
Certain critical data needs (e.g., loadings
of surface residues) are shared by both methods, whereas
other data needs (e.g., the fraction of the hand
inserted into the mouth during outdoor activities) are
more relevant to one approach (i.e., the SHEDS
methodology for this specific example).
The risk assessment implications of the model
features and data needs are also discussed in this
presentation.
Background Inorganic Arsenic Exposures in Children
Joyce S. Tsuji, Ph.D., DABT, Lisa Yost, MPH, DABT, Exponent, Bellevue, WA
Leila Barraj, Ph.D, Exponent,
Washington, DC
Understanding
where arsenic exposures fall with respect to natural
background is important for communicating the relative
magnitude of arsenic exposure and risk in relation to
everyday exposures. Arsenic
is naturally ubiquitous in the environment.
The primary background sources of inorganic arsenic
to the general population are food, water, and to a lesser
extent, soil. Using
reported inorganic arsenic data for food types and the
USDA food intake survey for children ages 1–6 years, the
probabilistically modeled average inorganic arsenic intake
was 3.2 µg/day
(95th percentile of 6.2 µg/day; 99th
percentile of 9.5 µg/day).
Foods contributing the most inorganic arsenic were
rice, other grains, and fruit.
One bowl of rice (1 cup cooked) contributes
nearly 4 µg
of arsenic. Inorganic arsenic intake by Asian or other populations with
much greater rice consumption compared with the typical
U.S. population would be considerably higher (e.g., 14 µg/day
for Japanese adults versus 3.2 µg/day
in U.S. adults; dietary arsenic estimates are not
available for Japanese children).
At an average arsenic level in drinking water in
the U.S. around 1–2 µg/L,
drinking water adds an additional 1–2 µg/day
assuming 1 L/day consumption.
EPA’s new drinking water standard for arsenic (10 µg/L) would contribute 10 µg/day.
By comparison, ingestion of soil containing arsenic
at a background level of 20 mg/kg would result in a
reasonable maximum estimate of 2 µg/day
(assuming 50 percent relative bioavailability or arsenic
in soil) and an average that is below 1 µg/day.
Thus, total background arsenic intakes are
available for placing arsenic exposures and risk in
context with naturally occurring sources.
Relationship
Between Childhood Arsenic Exposures and Cancer Risks in
the U.S. and Findings of an Ecological Arsenic Health
Effects Study
Floyd
Frost, Ph.D., Lovelace Respiratory Research Institute
Kristine Tollestrup, Ph.D, University of New Mexico, Dept.
of Family Medicine
Lucy Harter, Washington State Dept. of Health
Melissa Roberts, Lovelace Respiratory Research Institute
Arsenic
exposure studies conducted by the Washington State
Department of Health (WSDOH) in 1974 found that children
in the Ruston area near the ASARCO copper smelter excreted
arsenic in the urine at approximately the same
concentration as workers in the smelter. Urinary arsenic
levels as high as 0.68 ppm were observed in these children
in 1974. WSDOH
studies also found that: 1) younger children excreted
higher levels of arsenic than older children; 2) the level
of arsenic in the urine of children was proportional to
the distance of the residence from the smelter; and 3)
most of the exposure likely resulted from inhalation of
particles. Other
studies found that urinary arsenic levels in children were
lower during times of the day when the winds minimized
distribution of arsenic from the smelter, as well as
during a smelter strike.
These finding suggest that some of the arsenic
exposure might also have been due to dust in the
environment.
We
conducted a cohort study to determine whether childhood
exposure to arsenic increases overall mortality and
mortality due to lung and bladder cancer.
Cohort members were children who lived within 2.5
miles of the ASARCO copper smelter and arsenic refinery
for at least two years from 1907-1932. The cohort included 1,827 boys and 1,305 girls identified
from school census records.
Based on local school census records and the U.S.
Bureau of Census
records, we determined the duration of residence at each
location for the period 1907-1932.
Exposure intensity was computed as the total number
of years the child lived at residences <1.0 mile from
the smelter stack from 1907-1932.
Most of the arsenic exposures in this area were
from low-level emission from the processing plant rather
than the stack. Deaths
were identified from church or cemetery records, state
death records and, for more recent years, from the
National Death Index.
Overall follow-up was 58% for males and 48% for
females. A total of 712 males and 361 females were found to be
deceased. Of
these 46 males and 16 females had died from lung cancer.
In only one exposure intensity group (10 or more
years at <1.0 mile from the smelter) were Cox
proportional hazards ratios significantly higher than
1.00: all
causes of death (1.52), ischemic heart disease (1.77), and
external causes (1.93).
For girls, hazard ratios were not significantly
elevated for any cause of death in any exposure intensity
group.
We
have also conducted a nationwide exposure assessment for
drinking water arsenic in the U.S. and have related
arsenic exposure levels to lung, bladder, liver and kidney
cancer death rates for the U.S. for 1950-2000. The
analysis (MlwIN) relates exposure levels to outcomes,
adjusting for socio-economic and employment
characteristics of the county population.
Arsenic and the Cancer Slope Factor
Steven
H. Lamm, M.D., D.T.P.H., Consultants in Epidemiology and
Occupational Health, Inc., Washington DC, Tel:
202-333-2364
Background: Arsenic is a strange carcinogen in that it is well accepted as a
human carcinogen and shows little evidence of
carcinogenicity in other species.
Inhaled arsenic clearly causes lung cancer, and
ingested arsenic clearly causes skin cancer.
The standard risk model assumes that the study
population is one population and that the risk,
proportional to the dose, is the same for all people
within that population. Some analyses of the accepted studies suggest otherwise.
Materials and Methods: A
number of studies in the last ten years have suggested
that arsenic exposure causes bladder cancer.
The major study for analysis has been the
42-village study of Wu et al. (1989) from the Blackfoot
disease (BFD) endemic area of SW Taiwan.
The Morales et al. (2000) analysis has served as
the basis of the quantitative risk analysis by both the
EPA and the National Research Council.
Review of the well data for the villages reveals
two populations of villages based on water source
dependency [artesian vs. non-artesian]. Separate analyses have been carried out for each population.
US male bladder cancer mortality rates have also been
analyzed by median arsenic levels in drinking water
supply.
Results: There
is no change in bladder cancer mortality risk with
increasing arsenic exposure for villages not dependent
upon artesian wells.
There is a sharp dependency on arsenic level for
villages dependent on artesian wells.
The x-intercept for the artesian well dependent
villages is just above 200 ug/L.
These analyses are consistent with US data where no
change in bladder cancer mortality risk with increasing
arsenic exposure is seen for US counties over the range of
3 – 60 ug/L.
Conclusion: US and
Taiwan data both show no increase in bladder cancer
mortality rates with drinking water arsenic levels up to
the 100s of ug/L. The data are consistent with a risk model for arsenic as a
high-dose carcinogen or as a co-carcinogen.
The two largest epidemiological studies show no
basis for proposing a positive arsenic cancer slope factor
at US exposure levels, i.e., below a number of hundreds of
micrograms per liter.
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