# Cross-Sectional Exposure Assessment of Environmental Contaminants

# in Churchill County, Nevada

# 

# 

# 

# Final Report

# February 6, 2003

# 

# 

# 

Centers for Disease Control and Prevention

National Center for Environmental Health

Division of Environmental Hazards and Health Effects

Health Studies Branch

1600 Clifton Road NE, MS E23

Atlanta, Georgia 30333

1-888-232-6789

<EHHEinq@cdc.gov>

<http://www.cdc.gov/nceh/hsb>

# TABLE OF CONTENTS

###### Page

[Executive Summary](#executive-summary) 5

[Background](#Background) 8

[Methods](#methods-1) 8

[Results](#results-1) 12

[Discussion](#discussion) 19

[Conclusions and Recommendations](#conclusions-and-recommendations-1) 21

[Tables](#Table_1) 23

[References](#references) 40

[Maps](#Map1) 42

Appendices (Appendices can be accessed at
<http://www.cdc.gov/nceh/clusters/Fallon/study.htm>)

> A. Time line
>
> B. Expert Panel Report, February 15, 2001
>
> C. Investigation protocol

D. Biological laboratory methods

> E. Chemicals analyzed in environmental samples
>
> F. Description of eRoom technology
>
> G. Statistical methods
>
> H. Investigators, Collaborators and Funding Sources

## Tables

[1.](#Table_1) Participants Enrolled in the Churchill County Study of
Environmental Chemicals

[2.](#Table_2) Levels of Metals (μg/L) in Urine and Blood of People
Living in the United States and\
People Living in Churchill County, Nevada

[3.](#Table_3) Estimated Risk for Childhood Leukemia Associated with
Urine and Blood Levels of\
Metals (μg/L) for Case Children and Families Compared with Control
Children and Families Living in Churchill County

[4.](#Table_4) Nonpersistent Pesticide Levels (μg/L) in Urine of People
Living in the United States and\
People Living in Churchill County, Nevada

[5.](#Table_5) Estimated Risk of Childhood Leukemia Associated with
Urine Levels of Nonpersistent\
Pesticides for Case Children and Families Compared with Control Children
and Families Living in Churchill County

[6a.](#Table_6a) Persistent Pesticide Levels (ng/g lipid) in Blood of
People Living in the United States and\
People Living in Churchill County, Nevada

[6b.](#Table_6b) Polychlorinated Biphenyl Levels (ng/g lipid) in Blood
of People Living in the United\
States and People Living in Churchill County, Nevada

[7.](#Table_7) Risk Factors Potentially Associated with Exposure to DDT
and DDE (ng/g lipid)

[8a.](#table_8a) Estimated Risk of Childhood Leukemia Associated with
Blood Levels of Persistent Pesticide Levels (ng/g lipid) for Cases
Compared with Controls Living in Churchill County

[8b.](#Table_8b) Estimated Risk for Leukemia Associated with Blood
Levels (ng/g lipid) of Polychlorinated Biphenyls for Cases Compared with
Controls Living in Churchill County, Nevada

[9.](#Table_9) Volatile Organic Compound Levels (μg/L) in Blood of
People Living in the United States and People Living in Churchill
County, Nevada

[10.](#Table_10) The Estimated Risk of Childhood Leukemia Associated
with Blood Levels of Volatile Organic Compounds (μg/L) for Case Children
and Families Compared with Control Children and Families Living in
Churchill County

[11.](#Table_11) Selected Exposure Information Collected Through
Questionnaire and Interview from the Churchill County Study Population

[12.](#Table_12) Measure of Association with Infection Status Among Case
and Comparison Subjects

## Maps

[1.](#Map1) Geographic Location of Study Households, Churchill County,
Nevada.

[2.](#Map2) Distribution of Urinary Tungsten Results Among Churchill
County Residents at Time of Sample Collection, August 2001-February
2002.

> Map of Churchill County depicting household mean level of urinary
> tungsten, by location of residence at time of sample collection, with
> insert that shows distribution of results in immediate proximity of
> tungsten-related industry.

[3.](#Map3) Distribution of Tungsten Measured in Drinking Water Samples
Collected at Current Residence of Study Participant, August 2001-October
2002.

> Map of Churchill County depicting level of tungsten measured in tap
> water samples collected at each participant's residence at time of
> study enrollment.

[4.](#Map4) Distribution of Urinary Arsenic Levels Among Churchill
County Residents at Time of Sample Collection, August 2001-February
2002.

> Map of Churchill County depicting household mean level of urinary
> arsenic, by location of residence at time of sample collection.

[5.](#Map5) Distribution of Nonpersistent Pesticide Results Among
Churchill County Residents at Time of Sample Collection, August
2001-February 2002.

> Map of Churchill County depicting household summary measure of
> organophosphate levels among household members who gave urine samples
> by location of residence at time of sample collection. Locations of
> primary irrigation ditches and agricultural fields where pesticides
> were likely to be applied also are identified. (Summary measure is
> mean of household member's summed molar weights of organophosphate
> metabolites.)

[6.](#Map6) Distribution of Benzene Results Among Churchill County
Residents at Time of Sample Collection, August 2001-February 2002.

> Map of Churchill County depicting household mean level of benzene in
> blood samples, by location of residence at time of sample collection.
> Location of the jet fuel pipeline is also shown.

# EXECUTIVE SUMMARY

## Background

As part of its response to the elevated number of children in Churchill
County in whom acute lymphocytic leukemia (ALL) had been diagnosed, the
Nevada State Health Division (NSHD) requested technical assistance from
the Centers for Disease Control and Prevention (CDC). The purpose of the
subsequent collaborative investigation was to conduct a cross-sectional
exposure assessment to identify contaminants unique to the Churchill
County community. We examined exposures to certain chemical contaminants
known or suspected to cause cancer in humans, associated previously with
clusters of childhood leukemia, thought to be present in the local
environment, or because we had the analytic capacity to do so.

## Methods

We conducted a cross-sectional exposure assessment that included the
families of children already enrolled in an NSHD leukemia investigation
and comparison families that we identified through random digit dialing.
The study population included 14 ill children who resided in Churchill
County before diagnosis of their ALL or acute myelocytic leukemia. Case
families included parents and siblings, as well as other care-taking
adults in the home. Each case child was matched with four comparison
children by sex and age; the matched comparison parents also were
enrolled. A total of 205 participants visited a CDC clinic site in
Fallon, Nevada. Clinic staff collected extensive questionnaire
information and biologic samples (i.e., blood, urine, and cheek swab
samples). Environmental samples (i.e., indoor air, play yard soil,
household dust, and tap water) were collected from current homes and
previous homes for all case families. Environmental samples were also
collected from current homes for comparison families and previous homes
for one randomly selected matched comparison family for each case
family. Biologic and environmental samples were tested for heavy metals,
persistent and nonpersistent pesticides, polychlorinated biphenyls
(PCBs), and volatile organic compounds (VOCs). We also tested the
biologic samples for evidence of previous viral infections. We also
tested environmental samples for radon and radionuclides.

Considerable efforts were taken to ensure the quality of the analyses we
conducted. We convened statistical and genetic advisory groups to
provide external peer review and comment. In addition, a multi-agency
panel was formed to review all environmental results using a secure
electronic site for data presentation. We also hosted dedicated weekly
conference calls to facilitate communication among state and federal
partners.

In our cross-sectional analysis, we compared our laboratory results with
levels associated with adverse health effects in previous research. When
no such levels were available, we compared our results with the
geometric mean and 95^th^ percentile levels from the *Second National
Report on Human Exposure to Environmental Chemicals* *(National Exposure
Report),* which provides population-based reference ranges. The
environmental sample results were compared with published standards that
are identified for each chemical.

Appropriate statistical procedures such as cross-sectional descriptive
analysis, spatial analysis, and conditional logistic regression assessed
the probability that any elevated exposures could have resulted by
chance. During our case-comparison analysis, we initially considered the
13 out of 14 case children who had submitted biologic samples. We then
repeated the analysis using the nine children who had the most similar
disease profiles. The second analysis was limited to case children with
precursor-B cell lymphocytic leukemia that was diagnosed before they
were 6 years of age, and who lived in Churchill County for at least the
6 months before their diagnosis.

We further compared the infection status of all case children diagnosed
with each of the following to their matched comparison controls:
precursor-B or B-cell lymphocytic leukemia; precursor-B or B-cell
lymphocytic leukemia diagnosed before 6 years of age; precursor-B or
B-cell lymphocytic leukemia residing in Churchill County for at least 6
months before the leukemia diagnosis; and T-cell leukemia.

## Results

We found community-wide exposure to the element tungsten (geometric
mean=1.19 μg/L, 95% CI 0.89-1.59) compared with the *National Exposure
Report* reference of 0.08 μg/L (95% CI 0.07-0.09). We also found levels
of arsenic in urine samples ranging from nondetectable to 1180.40 μg/L.
Normal urine levels of arsenic are lower than 50 μg/L; a level \>200
μg/L is considered abnormal and may be associated with health effects.
Both tungsten and arsenic were identified in tap water samples
community-wide. Six additional metals (antimony, barium, cesium, cobalt,
molybdenum and uranium) were either slightly elevated above the
population geometric mean or else had more than 10% of their results
above the 95^th^ percentile level of the reference population or
health-based value. Although individual homes had environmental samples
with detectable levels of these metals, they were not elevated
community-wide.

Our cross-sectional analysis also identified five nonpersistent
pesticides (out of 31 nonpersistent pesticides or metabolites analyzed)
that were each above their respective 95^th^ percentile national
reference value in more than 10% of the Churchill County urine samples.
These pesticides include two organophosphate pesticide metabolites, two
chlorinated phenol pesticides, and a fungicide. We also identified an
aromatic hydrocarbon pesticide that was slightly higher than the
reference. We did not find community-wide elevations of any of these
nonpersistent pesticides in environmental samples.

Among 11 persistent pesticides analyzed, we found only DDE (geometric
mean=447.07 ng/g of lipid, 95% CI 355.09-562.87) to be above the
*National Exposure Report* reference of 260.00 ng/g of lipid (95% CI
234.0-289.0). We did not find elevated levels of DDT or DDE in
environmental samples, but levels in humans can reflect historical
exposure because these chemicals are stored in body fat. We also found a
geometric mean level of 10.46 ng/g of lipid of hexachlorobenzene in our
Churchill County study population compared with the national level of
less than the detection limit. However, the *National Exposure Report*
used an instrument detection limit of 60.5 ng/g of lipid, which is
substantially higher than our mean level. We found detectable levels in
18 of the 36 different PCBs that we analyzed; all were below the 95%
percentile of the *National Exposure Report*.

VOCs were not included in the *National Exposure Report* so we used
population reference levels from the third National Health and Nutrition
Examination Survey (1988-1994). We compared arithmetic means and 95% CIs
and found no community-wide elevated VOCs. Levels were similar among
case and comparison families. VOCs were not elevated in air samples.

In this study, testing for multiple viruses could not definitively
relate viral infection to the childhood leukemias in Churchill County.

We used conditional logistic regression to look for a relation between
any of the exposures and leukemia status. An odds ratio (OR) greater
than 1.00 suggests increased risk, and an OR equal to or less than 1.00
suggests no risk or decreased risk. A p-value less than 0.05 suggests
that chance alone is unlikely to explain the deviation from 1.00.
Tungsten (OR 0.78, p-value 0.57), arsenic (OR 0.60 p=0.22) and the rest
of the metals did not suggest increased risk. One of the PCB congeners
had an OR greater than 1.00 (p=0.01), while another congener had an OR
less than 1.00 (p=0.02). One VOC (ethylbenzene) suggested increased risk
(p-value 0.04) while another (tetrachloroethylene) suggested decreased
risk (p=0.004). From the interview information, we identified an
increased risk with older paternal age (OR 1.14, p=0.03). We found a
decreased risk among children in whom allergic rashes were diagnosed (OR
0.7, p=0.01).

## Conclusions and Recommendations

This investigation identified an ongoing environmental exposure of
concern among Churchill County residents. We confirmed that many people
living in Churchill County still receive significant arsenic exposure,
despite the general knowledge that Churchill County water exceeds
recommended levels of arsenic in drinking water. We recommend that
community members take advantage of alternative water sources until the
new water treatment facility is completed.

Biologic results also identified tungsten as a potentially unique
exposure within Churchill County. We are working with NSHD to further
define tungsten exposure in Nevada and to evaluate potential routes of
exposure. Because of our study findings, the National Institutes of
Health is considering tungsten as a priority chemical for toxicologic
research.

Although biologic results demonstrated a limited degree of elevated
pesticide exposure in the community, environmental testing did not
identify any sources of ongoing exposure. We recommend conservative use
of personal household pesticides and recommend that state public health
officials increase public education efforts about safe use of
pesticides.

Having found elevated levels of several chemicals, we now plan, with the
input of the Children's Oncology Group and other experts, to conduct
genetic testing to try to determine whether differences exist between
case families and comparison families in genes that are responsible for
the way these environmental chemicals are metabolized.

All participants have been given their personal results, as well as
information about how to minimize their environmental exposures. We
encourage participants to share elevated findings with their personal
health care providers.

# 

# 

#  

# BACKGROUND

[]{#Background .anchor}In February 2001, the Nevada State Health Officer
convened an Expert Panel to review existing evidence regarding an
increase in the number of children living in Churchill County, Nevada in
whom acute lymphoblastic leukemia (ALL) had been diagnosed (Appendix A).
The Expert Panel was familiar with previous investigations of ALL
clusters and recognized that all such investigations had failed to
identify a cause or an explanation for these excesses. However, because
so many cases had been identified in such a small population during such
a short time, the Expert Panel recommended that the State of Nevada
formally request assistance from the Centers for Disease Control and
Prevention (CDC) and the Agency for Toxic Substances and Disease
Registry (ATSDR) to evaluate environmental exposures potentially
associated with disease occurrence. The Expert Panel recommended that
the Nevada State Health Division (NSHD) take six follow-up steps in the
investigation of the excess occurrence of ALL in Fallon, Nevada
(Appendix B). The panel recommended that a multi-agency investigation
identify potential excess environmental exposures unique to the
community by a cross-sectional exposure assessment of selective
contaminants and an examination of contaminant releases into the local
environment with assessment of completed pathways for the case families
and recommended "collecting and banking biologic specimens for future
scientific investigations". CDC's National Center for Environmental
Health (NCEH) was asked to design and conduct a cross-sectional exposure
assessment of selected contaminants in Churchill County. This report
describes the methods and the results of the CDC investigation.

# METHODS

CDC collaborated with state and federal agencies to design a
cross-sectional exposure assessment protocol (Appendix C). We invited
families of the 14 case children who were already enrolled in the NSHD
leukemia investigation to participate (see [Table 1](#Table_1)). We
defined a case family as the case child and everyone else living in the
child's current home (i.e., all siblings, parents, guardians, and other
adults). The siblings were enrolled as possible surrogates for case
children whose leukemia status and current medications could influence
biologic sampling results. The case family also included any biologic
parents who were not living full time in the case family home but for
whom contact information was available.

We simultaneously enrolled comparison families from Churchill County
(with a goal of four comparison families for each case family) using
random digit dialing to contact the comparison families. Case children
and families were matched with comparison children and families
according to the birth year (+/-2 years) of the case child, sex of the
case child, and noncancer-diagnosed status of the comparison child at
the date of the case child's leukemia diagnosis. We defined a comparison
family as the matched comparison child and that child's parents,
guardians, or other care-taking adults living full time in the
comparison family home.

All participants were invited to visit a CDC-staffed clinic site in
Fallon from August 20 through October 31, 2001. During that visit we
collected extensive questionnaire information about recent and
historical exposures and medical history and also collected biologic
samples (blood, urine, and cheek swab samples). Biologic samples were
tested at CDC laboratories for heavy metals, persistent and
nonpersistent pesticides, polychlorinated biphenyls (PCBs), and volatile
organic compounds (VOCs), as well as for infectious disease markers of
past infection, such as Epstein-Barr virus and human T-cell leukemia
virus. During the clinic visit we also arranged appointments for
environmental sampling in participant homes. Laboratory methods are
referenced or described in Appendix D. DNA was extracted from blood and
cheek cells and stored by CDC for future study of candidate genes
involved in metabolizing carcinogens and in DNA repair from damage by
environmental exposures.

A 15^th^ case child was identified and invited to enroll in December
2001. Biologic and questionnaire data collection was completed in
February 2002. Total study enrollment comprised 205 participants from 14
case families and 55 comparison families. One case child died before any
biologic samples were collected from the child; however the child's
family and four matched comparison families were included in the
analysis. Although one case family declined participation, we had
already enrolled four matched comparison families for that family and we
included their information in the cross-sectional analysis but not in
the case-comparison analysis. We enrolled all 15 of the eligible case
siblings (age range:1-30 years) who were living in the case families'
homes.

### Genetic Information

In collaboration with NSHD, we requested cytogenic test results of
samples collected from case children before their treatment began and
analyses that were performed as part of their treatment protocol. We
obtained results for 13 of the 14 case children who consented to
participate. We obtained information about the type of leukemia (T-cell
or precursor-B ALL) for all 13 case children and information about the
types of chromosomal abnormalities found in three case children. For
four case children, specimens were stored for later analyses. The reason
for the small number of case children who had results for translocations
and for which residual specimens were stored is that this information
and specimen storage were assured only for the children who were entered
into a Children's Oncology Group protocol that specifically requested
storage of specimens and provided for testing for specific
translocations. Similarly, the complement of diagnostic, pre-treatment
specimens was not available for infectious agent testing.

### Environmental Sampling

Using standardized protocols (Appendix E), the Nevada Department of
Environmental Protection (NDEP) collected environmental samples,
including indoor air, play yard soil, and household dust from case
families' current and previous residences within Churchill County,
current residences of all comparison families, and previous Churchill
County residences of one out of four comparison families. Tap water
samples were collected by the United States Geological Survey (USGS). We
sampled all current residences of those case families still living in
Churchill County at date of enrollment (n=11), all previous homes in
which case families had lived since 1 year before the date of birth of
the case child (n=8), all current (at date of enrollment) comparison
families' homes (n=55), and the previous homes of one randomly chosen
comparison child for each case child (n=6). Among the 36 eligible
previous residences, eight case homes, and 14 comparison homes were not
available for sampling. Current and previous residences outside of
Churchill County were not sampled. Environmental sample collection,
excluding tap water samples, was completed in March 2002. Tap water
sample collection was completed in September 2002. Household samples
were tested for heavy metals, persistent and nonpersistent pesticides,
PCBs, VOCs, radon, and radionuclides. Environmental samples were
analyzed by USGS, the U.S. Environmental Protection Agency (EPA) Region
IX, the Nevada Department of Agriculture, and several contract
laboratories (Appendix E).

### External Peer Review 

To further enhance the strength of this investigation, CDC convened
several advisory groups to provide external peer review and comment. We
established a statistical advisory group that wrote a statistical plan
and met regularly to review questionnaire and biologic results. We
convened a genetic advisory group that included representatives from
Children's Oncology Group. We also formed a multi-agency Data
Interpretation Group to review all environmental results using a secure
electronic site for data presentation (Appendix F). CDC also hosted
dedicated weekly conference calls to facilitate communication among
state and federal partners. To further enhance communication with NSHD,
CDC contracted to place a communication liaison in Carson City for 15
months and contracted a specialist to prepare a communication plan for
NSHD.

### Cross-sectional Analysis Methods

The cross-sectional analysis included all study participants. We used
descriptive and spatial analysis to compare our biologic and
environmental sampling results with a reference standard. [Map 1](#Map1)
shows the geographic location of study households. We used the geometric
means and 95% confidence intervals (CIs) under the assumption that the
data approximates a log-normal distribution. The estimate of the
geometric mean and CI is based on a statistical model that controls for
the possible correlation of observations within a family (i.e., a
variance components model), when appropriate. Statistical methods are
further described in Appendix G.

For biologic samples, we compared our results to a reference level known
to be associated with adverse health effects (e.g., blood lead levels or
urine arsenic levels) when such levels are known. When no
health-effect-based reference level was available, we compared the
Churchill County geometric mean value to the geometric mean from the
*Second National Report on Human Exposure to Environmental Chemicals*
(*National Exposure Report*) (<http://www.cdc.gov/exposurereport>),
which is based on population data collected as part of the National
Health and Nutrition Examination Survey (NHANES)
([http://www.cdc.gov/nchs/nhanes.htm)]{.underline}. If the lower
boundary of the Churchill County CI was higher than the upper boundary
of the *National Exposure Report* CI, then we considered that chemical
to be elevated in our study population. This is designated as "H" on
tables that report cross-sectional results. If the Churchill County CI
overlapped that in the *National Exposure Report*, then we considered
the chemical to be consistent with national estimates. If the upper
boundary of the Churchill County CI was below the lower boundary of the
*National Exposure Report* CI, then we considered the chemical to be low
in our study population; we designated this by an "L" on the tables that
report cross-sectional results. We made this comparison as a
conservative first step in evaluating our study results. We also looked
at the percentage of study participants that exceeded the 95^th^
percentile level of that chemical in the *National Exposure Report*. If
more than 10% of our study population exceeded the 95^th^ percentile
from the *National Exposure Report*, we classified that chemical as "H"
in our study population. Chemical results that do not have a
health-based reference value, and were not measured in the *National
Exposure Report*, were compared with reference levels found in the
peer-reviewed literature---such references were available. The source of
the reference for each individual chemical is provided on the results
tables in this report.

For environmental samples, the Data Interpretation Group reviewed
summary reports prepared by ATSDR's Federal Facilities Information
Management System (FFIMS) for each site tested and summary data for each
chemical. These reports were posted in a secure web-based meeting space
for review. Comments posted from agency representatives included a vote
about whether the data set included any chemical levels of concern. We
determined this by comparing the concentration of contaminants detected
in air, water, or soil against ATSDR's health-based values. These values
often are based on animal studies because relevant human data are
lacking and they are designed to be orders of magnitude lower than
levels known to produce adverse health effects. Chemical levels that
were above the reference level were reviewed in detail. Site summaries
written at the time samples were collected often provided information
that would explain the elevated chemical levels, such as recent spraying
of pesticides. Members of the Data Interpretation Group often consulted
relevant scientific literature to determine whether comparison values
were up to date and whether site-specific exposures could pose a hazard
to public health.

If no ATSDR comparison value was available, FFIMS provided, in a
hierarchical fashion, comparison levels from EPA Region IX, EPA Region
III, or EPA Region VI. If available, levels from EPA Region IX were used
first because it is the region in which Nevada is located, and these
levels represent the level at which chemicals would most likely be
found. If neither ATSDR nor EPA Region IX had levels for a given
chemical, values from EPA Region III were used. EPA Region III was
selected because of that region's strict regulations. Finally, if
comparison levels were not available from any of these sources, levels
from EPA Region VI were used. This region was selected because it is the
most geologically similar to Region IX. If no comparison level of any
kind was available for a chemical, the members of the Data
Interpretation Group who had expertise with that chemical would make a
determination based on the result, site summaries, known adverse health
effects, and professional expertise.

### Case-comparison Analysis Methods

Our case-comparison analysis included 14 case families and their 51
matched comparison families. Siblings were included in portions of the
case-comparison analysis. Results excluding siblings are so labeled. We
used conditional logistic regression to compare exposure between case
and comparison families. Conditional logistic regression was performed
for quantitative variables assuming a log-linear relation between the
variable and the odds of disease. We standardized each independent
variable by dividing each value by the standard deviation of that
variable calculated using the entire Churchill County study population.
As a result, odds ratios (ORs) for quantitative variables correspond to
an increase in dose corresponding to one standard deviation in the study
population. When 40% or more of the study participants had levels below
the limit of detection for any quantitative variable, we grouped the
variables into two categories: at or below the limit of detection and
above the limit of detection. For these variables, ORs measure the
association between case and comparison status and the presence of
having detectable levels of the chemical of interest.

Conditional logistic regression models were used to model the
probability of experiencing an exposure while conditioning on the
matching strata that are apparent in the data. The resulting ORs provide
a means of exploring the relation between disease and exposure. An OR of
1.0 indicates no differences between the two groups with respect to the
exposure variable. ORs that are statistically significantly different
from 1.0 (as assessed by a p-value) indicate that one group has higher
(or lower) odds of having been exposed. In this study, small p-values
(e.g., p-values \< 0.01) indicate statistically significant differences
in the exposure variable between the case and comparison groups. An OR
also is considered statistically significant when the CI around that
point estimate does not include the number one. LogXact software from
Cytel Corporation was used to fit the conditional logistic regression
models (LogXact 4, 1996-2000).

During our analysis, we initially considered all 13 case children with
biologic samples. We then repeated the analysis using the nine children
who had the most similar disease profiles. The second analysis (referred
to in the Results section as the restricted case definition) was limited
to case children with pre-B-cell lymphocytic leukemia diagnosed before
they were 6 years of age and who had lived in Churchill County for at
least the 6 months before their diagnosis. Six months of exposure to a
carcinogen before a cancer diagnosis is considered a conservative
latency period for a pediatric cancer (Ford 1993). Restricted case
definition analysis included only 34 comparison children matched to the
nine case children.

Individual results of biologic and environmental sample analysis were
reported back to each study participant before release of aggregate
results.

# RESULTS

On August 20, 2002, CDC released preliminary results of heavy metal
analysis on blood and urine samples. Although the remaining biologic
sample analyses had not been completed, the metals results were released
to participants and to the community because arsenic and tungsten levels
were markedly above reference levels. The median tungsten level in the
study population was 0.97 μg/L compared with 0.10 μg/L in the 1999
NHANES, which was the most current population reference available in
August 2002. Levels among case and comparison children and families were
similar (case children median = 1.94 μg/L; comparison children median =
2.36 μg/L, and case family median =1.00 μg/L; comparison family median =
0.97μg/L). Almost 80% of the Churchill County participants had tungsten
levels above the NHANES 90^th^ percentile (0.32 μg/L). Upon receiving
the biologic results, CDC contracted with USGS to collect and measure
tungsten in tap water samples from participants' homes, and petitioned
the National Toxicology Program of the National Institutes of Health to
prioritize research regarding the health effects of tungsten exposure.

We also informed the Churchill County community that arsenic levels in
the study participants ranged from less than the limit of detection to
1180.40 μg/L, with a median level of 37.40 μg/L; normal urine levels of
arsenic are lower than 50 μg/L; levels \>200 μg/L are potentially
associated with adverse health effects (Haddad 1998). Individual
participants were advised to limit their exposure to water containing
arsenic.

By December 2002, CDC had received results of all the biologic and
environmental samples that the many state and federal laboratories had
analyzed, except for speciated arsenic results for biologic samples. The
results are presented below divided into chemical categories (i.e.,
metals, nonpersistent pesticides, persistent pesticides, PCBs and VOCs)
and infectious disease categories. Within each category, results of the
cross-sectional analysis and the case-comparison analysis are presented
separately.

We reviewed the results as both creatinine corrected and noncreatinine
corrected, as well as lipid adjusted and lipid unadjusted. In this
report, we present noncreatinine corrected results for metal and
nonpersistent pesticide levels in urine samples, lipid-adjusted results
for persistent pesticide and PCB levels in serum samples, and results
not adjusted for lipids for VOCs analyzed in blood samples.

## Metals 

### Cross-sectional Analysis

[Table 2](#Table_2) shows the geometric mean level in biologic samples
for the 16 metals we analyzed in the Churchill County study
participants. Three of these metals (cadmium, lead, and mercury) were
analyzed in both blood and urine samples; 12 other metals were analyzed
in urine samples; selenium was analyzed in serum samples. We used
health-based reference levels to determine excess exposure to cadmium
(Lauwerys 2001), lead (Lauwerys 2001, Goldfrank 2002), mercury
(Goldfrank 2002), arsenic (Haddad 1998, Goldfrank 2002), selenium
(Hogberg 1986), and nickel (White 1998). For eight of the metals, the
geometric mean and the 95^th^ percentile reference level are available
from the *National Exposure Report*. Chromium and manganese do not have
any available reference levels for comparison.

Eight of the metals (antimony, arsenic, barium, cesium, cobalt,
molybdenum, tungsten and uranium) measured in urine are classified as
"H" (Table 2). Six of these metals (antimony, barium, cesium, cobalt,
molybdenum and tungsten) are classified as high because the lower
boundary of our study geometric mean is higher than the upper boundary
around the confidence interval for the geometric mean of the *National
Exposure Report*. For three of these metals (barium, cesium, and
tungsten) more than 10% of the levels also are above the 95^th^
percentile in the *National Exposure Report*: barium, 14% above; cesium,
12% above; and tungsten, 68% above. The study geometric mean for uranium
is actually lower than the *National Exposure Report* geometric mean.
However, uranium is classified as "H" on Table 2 because 25% of the
Churchill County levels are above the 95^th^ percentile level in the
*National Exposure Report*. Similarly, arsenic is classified as "H"
because 34% of our study participants are above the health-based
reference level, although the geometric mean level of our study
participants is below the health based reference level. Although eight
metals are classified as high, only tungsten has a study population
geometric mean that exceeds the 95^th^ percentile level in the *National
Exposure Report*. The following results further describe tungsten,
arsenic, and uranium exposure in the cross-sectional analysis.

**Tungsten** was detected in 98.5% of our study population samples; the
geometric mean was 1.17 μg/L (95%CI 0.93-1.46). In comparison, tungsten
was detected in 76% of the participants sampled for the *National
Exposure Report*, where the geometric mean was 0.09 μg/L (95%CI
0.09-0.1). [Map 2](#Map2) shows the distribution of household geometric
mean tungsten levels according to residence at time of study enrollment.
Results of tap water sampling from 76 residences ranged from 0 to 217.3
ppb; no reference level is available for tungsten in drinking water.
[Map 3](#Map3) shows the distribution of tap water results at each study
participant's current residence. Individual levels of urinary tungsten
and tungsten levels in tap water samples were not correlated (Spearman
correlation coefficient=0.09, p=0.18), even when stratified by source
(well or public) and by treatment (reverse osmosis treatment, yes or
no). Our questionnaire did not collect individual information about
amount of drinking water consumed or the variety of potential drinking
water sources (e.g., home, school, workplace) for a person accessing
drinking water.

Naturally occurring **uranium** was detected in 86.7 % of our study
population urine samples; the geometric mean was 0.02 μg/L (95% CI
0.02-0.03). In comparison, uranium was detected in 72.0% of the
participants sampled for the *National Exposure Report*, where the
geometric mean was 0.048 μg/L (95% CI 0.04-0.06). Uranium levels in tap
water samples ranged from 0.004 μg/L to 290 μg/L; the National Drinking
Water Standard for uranium will be 30 μg/L as of 12/08/03
(<http://www.epa.gov/ogwdw/mcl.html>). Individual levels of uranium in
urine samples were slightly correlated (Spearman correlation
coefficient=0.36, p=0.0001) with uranium levels in residential tap
water.

We detected **arsenic** in 99.5% of our study participants' urine
samples. Arsenic levels are not included in the *National Exposure
Report*. Arsenic levels in the study population ranged from less than
the limit of detection to 1180.40 μg/L, with a median level of 37.40
μg/L. The geometric mean was 34.61 μg/L (95% CI 28.07-42.68). Arsenic
levels varied among family members within a single household. [Map
4](#Map4) shows the distribution of household geometric mean level of
arsenic in urine samples. Tap water levels of arsenic varied from 2.0 to
874 μg/L; the National Drinking Water Standard for arsenic is 50 μg/L
(<http://www.epa.gov/ogwdw/mcl.html)>. Individual levels of arsenic in
urine samples were only slightly correlated with residential tap water
levels (Spearman correlation coefficient=.21, p=0.007).

### Case-comparison Analysis

[Table 3](#Table_3) shows the OR and p-values for logistic regression
models comparing case children and case families with their matched
controls. Using conditional logistic regression and limiting our
analysis of **tungsten** exposure to case families, excluding siblings,
and their matched comparison families, we found no relation between
leukemia and tungsten exposure (OR 0.96, 95% CI 0.77-1.24, p=0.85). For
case parents and comparison parents the OR was 1.06 (95% CI 0.66-1.70,
p=0.82); for case children and comparison children the OR 0.78 (95% CI
0.33-1.86, p=0.57). Results were similar (OR 1.16, 95% CI 0.59-2.03,
p=0.78) when using the restricted case definition children only.

For **uranium**, we found no difference in exposure among case families,
excluding siblings, and comparison families (OR 1.06, 95% CI 0.77-1.44,
p=0.76), nor among case versus comparison restricted definition study
children (OR 1.24, 95% CI 0.63-2.45, p=0.09). We identified a slightly
increased risk for exposure among restricted case definition case
families, excluding siblings, and comparison families (OR 1.91, 95% CI
1.11-3.28, p=0.002).

**Arsenic** exposure was somewhat lower among case families (geometric
mean 26.24 μg/L (95% CI 18.59-37.02) than comparison families (38.12
μg/L (95% CI 31.23-46.53). Case families, excluding siblings, were less
likely to be exposed to arsenic (OR 0.64, 95% CI 0.47-0.98, p=0.03) than
were their matched comparison families. When using the restricted case
definition the exposure among case children remained lower than among
comparison children, but the difference was not statistically
significant.

## Nonpersistent Pesticides

### Cross-sectional Analysis 

[Table 4](#Table_4) shows the geometric mean levels of 31 nonpersistent
pesticides and pesticide metabolites analyzed in urine samples collected
from the Churchill County study population. Nineteen of the metabolites
relate to exposure to cholinesterase-inhibiting pesticides (e.g.,
organophosphate and carbamate pesticides), four metabolites originate
from chlorinated phenol pesticides (e.g., hexachlorobenzene), three
metabolites are specific to herbicides (e.g., atrazine), one metabolite
is specific to pyrethroids, one compound is specific to a fungicide, and
three compounds relate to exposure to insect repellents (e.g., DEET).
Although 24 of the pesticide metabolites were analyzed for the *National
Exposure Report*, only nine were detected in \>60% of samples, which is
the detection level necessary to calculate the geometric mean. Five of
the pesticides we measured (chlorpyrifos, diethylthiophosphate,
2,4,5-trichlorophenol \[1TB\], 2,4,6-trichlorophenol \[3TB\] and
2-naphthol) are above the reference geometric mean (Table 4). The
compound specific to a fungicide (o-Phenylphenol) could not be compared
to a reference geometric mean but 18% of the Churchill County
participants were above the *National Exposure Report*. Four of the
pesticides are below the national reference; most of the pesticides are
similar to the national reference. Among the five pesticides with no
available reference level, all Churchill County median levels were below
the level of instrument detection. No results were reported for the
metabolite alachor mercapturate. [Map 5](#Map5) shows the distribution
of the household geometric mean of summed individual levels of
organophosphate metabolites not adjusted for creatinine.

Two **chlorinated phenol** pesticides, 1TB and 3TB, were higher (median
5.87 μg/L and 4.78 μg/L, respectively) than levels in the *National
Exposure Report* (median 0.80 μg/L and 2.45 μg/L, respectively). 1TB was
detected in 71.3% of our study population samples; the overall geometric
mean was 4.48 μg/L (95% CI 3.65-5.50). This compares with detection of
1TB in 88% of the participants sampled for the *National Exposure
Report*, where the geometric mean was 1.19 μg/L (95% CI 1.00-1.41). 3TB
was detected in 56.4% of our study population samples; the overall
geometric mean was 4.58 μg/L (95% CI 3.69-5.69). This compares with
detection of 3TB in 81% of the participants sampled for the *National
Exposure Report*, where the geometric mean was 2.85 μg/L (95% CI
2.58-3.15).

Environmental sampling for nonpersistent pesticides included analysis
for 1TB and 3TB in soil. Of 79 samples tested, two had minimally
detectable levels of both 1TB and 3TB. We tested for 15 other
chlorinated phenol compounds; low levels were detected in soil but all
below reference levels.

### Case-comparison Analysis

[Table 5](#Table_5) shows the results of conditional logistic regression
of the nonpersistent pesticides that had detectable percentages
sufficient to calculate ORs and p-values.

For the chlorinated phenol **1TB**, the geometric mean for the case
families was 4.08 μg/L (95% CI 2.68-6.21) and 4.63 μg/L (95% CI
3.61-5.94) for the comparison families (p=0.69). Exposure to 1TB was not
associated with leukemia status (all study children OR 0.57, p=0.09).
Restricted case definition comparison was similar.

For **3TB** the geometric mean for case families was 4.93 μg/L (95% CI
2.63-9.24) and for comparison families 4.31 μg/L (95% CI 3.22-5.77,
p=0.23). Because more than 40% of the results for 3TB were below the
limit of instrument detection, the OR and corresponding p-values could
be calculated only for case children; results are similar to 1TB.

## Persistent Organic Compound Results 

### Cross-sectional Analysis

[Table 6a](#Table_6a) shows the geometric means of the 11 persistent
pesticides, and [Table 6b](#Table_6b) shows the geometric means of the
36 PCBs. Ten of the persistent pesticides have geometric mean and 95^th^
percentile levels reported in the *National Exposure Report*. There is
no reference level for dieldrin.

Nine of the persistent pesticides had geometric mean levels below the
national geometric mean. Only
1,1-dichloro-2,2-bis(*p*-chlorophenyl)-ethylene (**DDE**), a breakdown
product of 2,2-bis(*p*-chlorophenyl)-1,1,1-trichloroethane (DDT) was
elevated (median 445.27 ng/gram lipid) in our study population, compared
with the *National Exposure Report* (median 226.00 ng/g lipid).

We calculated medians and geometric means for subsets of the total study
population according to potential sources of historical exposure (see
[Table 7](#Table_7)).

Of the 36 PCBs, 22 have reference levels in the *National Exposure
Report*; for the remaining PCB congeners, relevant reference levels are
not available. Six of the 22 congeners (PCBs 28, 52, 66,101, 156, and
187) had geometric means that were above the *National Exposure Report*
geometric mean levels. None of the PCB congeners exceeded the 95^th^
percentile reference levels.

Persistent pesticides were analyzed in soil and dust samples. During
review of the PCB mixture results in soil, the Data Investigation Group
found that the analytical limit of detection for our levels were
significantly higher than the available comparison values. The high
detection limits probably resulted from matrix interference, commonly
encountered in the analysis of soil and dust samples.

Data Investigation Group representatives from ATSDR took the lead in
identifying an alternate comparison level that would allow PCB results
to be more accurately interpreted. Using a conservative EPA clean-up
goal value of 1.0 ppm, the detection limits for the seven aroclors for
each household were summed. For most of the households, the summed
detection limits were lower than the EPA value of 1.0 ppm. Four
households, however, had summed detection limits higher than the
comparison value, suggesting that the dust samples from these households
had PCB levels approaching 9.0, 2.4, 2.4, and 2.1ppm. The Data
Investigation Group reviewed PCB results in other environmental and
biologic matrices. Summed detection limits for PCBs in soil did not
exceed 1.0 ppm. Levels of PCB congeners in biologic samples collected
from members of three of the households did not exceed comparison
values. One member of the fourth household had slight elevations in
three congeners, 146, 170, 180, but reported related occupational
exposures. No members of the household with the highest summed detection
limits had PCB levels above comparison levels. The Data Investigation
Group determined resampling or reanalyzing dust samples from the four
households whose summed detection limits for arochlor exceeded 1.0 ppm
was not necessary.

One persistent pesticide (dieldrin) was elevated in environmental
samples collected from residential play yard soil. The maximum result
reported was 0.19 ppm. Although this level exceeds the ATSDR Cancer Risk
Evaluation Guide (an estimated level of a chemical that is expected to
cause no more than one excess cancer in a million people exposed over a
lifetime) (0.04 ppm), it is within an acceptable risk range for
long-term (chronic) exposures (ATSDR Public Health Guidance Manual). In
addition, this level is less than the ATSDR chronic oral child
Environmental Media Evaluation Guide (the concentration of a chemical in
a particular medium e.g., air, water, soil that is calculated from ATSDR
minimal risk levels for non-cancer health effects) (3 ppm) (ATSDR Public
Health Guidance Manual).

### Case-comparison Analysis

[Table 8a](#table_8a) and [8b](#Table_8b) show the results of
conditional logistic regression of the three persistent pesticides that
had detectable percentages sufficient to calculate ORs and p-values.

Geometric mean for DDE was 302.9 ng/g lipid (95% CI 125.43-731.45) for
case families and 501.28 ng/gm lipid (95% CI 440.23-585.75) for their
comparison families (p=0.08). Comparisons of all matched cases did not
appear to associate DDE exposure with leukemia (OR 0.53, p=0.26).

Conditional logistic regression analysis identified seven PCB congener (
\# 18, 28, 52,101, 118, 196 and 206) with significant p-values (Table
8b).

## Volatile Organic Compound Results 

### Cross-sectional Analysis

[Table 9](#Table_9) shows the arithmetic mean levels of the 12
creatinine unadjusted VOCs analyzed in this study. Because VOCs were not
included in the *National Exposure Report* reference levels are taken
from population-based studies published in the peer-reviewed literature
(Ashley 1994, Ashley 1996, and Churchill 2001). Two of the Churchill
County levels (styrene and tetrachloroethylene) were slightly higher
than the reference arithmetic mean but lower than the 95^th^ percentile.
[Map 6](#Map6) shows the distribution of household geometric mean levels
of benzene in blood samples collected from Churchill County residents.

Air of 77 households was sampled for VOCs. None of the results suggested
a community-wide exposure to any of the 61 VOC analytes we measured. The
few VOC analytes detected in most of the households sampled were either
common household VOCs (e.g., acetone, ethanol) or were lower than
comparison levels. ATSDR screening levels and EPA regulatory or
recommended levels were used as comparison values.

Two homes had elevated levels of tetrachloroethylene. The comparison
value used to screen tetrachloroethylene was 3.3 μg/m^3^ from EPA Region
IX. The two homes had levels of 244 and 326 μg/m^3^. In reviewing site
summaries written at sample collection, we determined that dry-cleaned
clothes had recently been brought into one house. The site summary for
the other household did not indicate recent dry-cleaning. However,
questionnaire data indicated that the father works as a mechanic and
therefore would be likely to bring tetrachloroethylene residues into the
house on his clothes.

Levels of all others VOCs were determined by the Data Investigation
Group to be below a level of concern.

### Case-comparison Analysis

[Table 10](#Table_10) shows the results of conditional logistic
regression of the nine VOCs that had detectable percentages sufficient
to calculate ORs and p-values.

We found an OR of 0.35, p-value 0.004, when comparing
tetrachloroethylene exposure among case and comparison families,
excluding siblings. This suggestive protective effect did not remain
statistically significant when we compared only study children, or
restricted case definition children. An increased risk, but with wide
CIs, associated with exposure to ethylbenzene was observed among case
children matched to comparison children (OR 2.67, 95% CI 1.04-6.84,
p-value 0.04).

Ethylbenzene was detected in 10 of 77 households, with a mean level of
8.36 ug/m^3^. None of the households exceeded the EPA-recommended level
of 1100 μg/m^3^. The maximum level detected was 20 μg/m^3^.

## Questionnaire and Interview Results 

### Cross-sectional Analysis

We collected extensive information from all participants about
residential, occupational, medical, and travel histories, including
details of exposures from before pregnancy until diagnosis. Case
children (seven girls and seven boys) and matched comparison children
ranged in age from 2 years to 19 years at diagnosis and from 3 years to
20 years at sample collection. At enrollment, case mothers were 24-50
years of age, and case fathers were 31-58 years; comparison mothers
ranged in age from 22 to 57 years, and comparison fathers from 25 to 58
years. The complete questionnaire is included with the study protocol
(Appendix C). [Table 11](#Table_11) lists selected descriptive
information collected from all study participants.

### Case-comparison Analysis

Using conditional logistic regression to evaluate paternal age, we found
an association between leukemia diagnosis and fathers being older at the
time of the study child's birth (OR 1.14, 95% CI 1.01-1.29). This
difference persisted for the restricted case definition group (OR 1.19,
95% CI 1.02-1.39). We found no association between case status and
maternal age.

Case children were historically less likely to have been
physician-diagnosed with an allergic skin rash (OR 0.067, 95% CI
0-0.46), although this estimate is considered unstable because no case
children answered yes to the question. Several household recreational
exposures occurred more frequently among comparison than case families.
For example, comparison adults were more likely to use glues or
adhesives daily (OR 0.74, 95% CI 0.18-2.7).

## Infectious Disease Results

Because some studies suggest that certain viruses might influence the
development of leukemias and other cancers (Greaves 2000, Smith 1997,
CDC 1993, McNally 2000, Neglia 2000), we evaluated participants for
evidence of certain infections. This evaluation included testing blood
samples for the viruses described below, which are known or suspected to
be associated with leukemia. The tests show whether a person was
infected with the viruses at any time before blood was drawn. The tests
cannot distinguish whether a person was infected before or after he/she
developed leukemia.

### Epstein-Barr Virus (EBV)

Blood samples from all community participants were tested for EBV. EBV
is a common virus that infects most people before they reach middle age
(Epstein 1996, Schooley 2000). In the United States, as many as 95% of
adults aged 35-40 years have been infected. Risk of EBV infection
increases with age. Most people infected with EBV have only mild
symptoms or never get sick. Thus, many people never know they have been
infected. Some EBV-infected people develop infectious mononucleosis or
"mono". In the Churchill County study, some participants had evidence of
past (more than three months before they gave blood for the study) or
more recent (three months or less before they gave blood samples) EBV
infection. Results for others suggested that they had never been
infected with EBV. The age-related distribution of EBV serology among
the study participants was not different than expected.

### Case-Comparison Analysis: EBV

Using conditional logistic regression, this study further compared the
results of EBV testing for all 13 case children submitting blood samples
and their 47 matched controls. ([Table 12](#Table_12)). The analysis
could not definitively relate EBV infection to the childhood leukemias
in Churchill County (OR 0.41), 95% CI (0.07-1.92). EBV infection seemed
to occur less frequently among the children with leukemia than among the
comparison children. However, the study could not conclude that EBV
infection either protected against or increased the risk for the
childhood leukemias.

### Other Viruses

The study also examined blood samples for a group of viruses called
"retroviruses". Samples from all children diagnosed with childhood
leukemia were tested. For each of these children, samples from two
comparison children also were tested to help interpret the results. The
study employed a research test (ampRT) that screens for a number of
retroviruses. Samples also were analyzed by other laboratory methods,
including research tests, for these retroviruses: human T-lymphotropic
virus type 1 (HTLV-1); human T lymphotropic virus type 2 (HTLV-2);
feline leukemia virus (FeLV); avian leukosis virus (ALV). HTLV-1 is
associated with a rare form of leukemia, adult T-cell lymphoblastic
leukemia/lymphoma. HTLV-2 is a related virus. However, both HTLV-1 and
HTLV-2 infections are uncommon in the United States. FeLV is found in
cats with leukemia but has not been reported in humans with leukemias.
ALV is a bird virus that has not been reported to infect humans.
However, because humans have contact with birds, the study also tested
blood samples for ALV. We found no evidence of any of these viruses or
of viral activity in any of the participants.

### Other Possible Markers of Infection

We analyzed certain interview and questionnaire items that might suggest
exposure to infections. However, those analyses did not identify any
specific infectious risks for childhood leukemia in the study
population.

# DISCUSSION

This report describes the methods and results of a multi-agency
state-of-the-art investigation to determine whether environmental
exposures in Churchill County, Nevada posed a risk to human health. CDC
led a cross-sectional study to determine whether unrecognized chemicals
were present in the community, and whether any associations existed
between environmental exposures and the cluster of children with
leukemia that had been identified in Churchill County. Before this
investigation, the community was aware that water from municipal and
private wells contained excess amounts of arsenic. The community also
was concerned about potential exposures to VOCs because of their
proximity to the Fallon Naval Air Station. In addition, the community
voiced concerns about underground nuclear testing that had historically
taken place in Nevada.

Our study found that most chemicals measured in biologic and
environmental samples were comparable with reference levels. This
investigation also identified that the elements tungsten and arsenic,
two chlorophenol pesticides, two organophosphate metabolites and the
persistent pesticide metabolite DDE were elevated above reference levels
in the biologic samples. Tungsten and arsenic also were elevated in tap
water samples; pesticides were not elevated in any of the environmental
samples.

Neither tungsten nor arsenic has been previously associated with ALL.
Within our study population, levels were not higher among case families
than among comparison families, although people may react differently to
excess exposures based on their own genetic make-up. We found a strong
correlation (Spearman correlation coefficient=0.67, p-value \< 0.0001)
between tungsten and arsenic levels in urine samples and between
tungsten and arsenic levels in tap water samples (0.83, p-value
\<0.0001). However, we found only a slight correlation (p=0.21) between
urine arsenic and tap water arsenic and no correlation (p=0.18) between
urine tungsten and tap water tungsten. Water treatment processes that
remove arsenic from drinking water are assumed to be equally effective
for removing tungsten. Reverse osmosis and ion exchange treatment
systems are effective for removing arsenic V (98-99%) and, to a lesser
extent, arsenic III (46-75%). Based on its relation to chromium on the
periodic chart, tungsten probably reacts similarly to treatment as
chromium. Cr(III) and Cr(VI) are both well removed by reverse osmosis
treatment and ion exchange, removals range from 96%-99% (Faust 1998).

Our cross-sectional study also identified increased levels of two
chlorophenol pesticides that may be associated with exposure to
hexachlorobenzene, or pentachlorophenol, or the pesticide lindane, which
is dispensed by prescription to treat head lice and scabies. Although
these levels were above our reference level, these levels have not been
associated with adverse health effects. Once again, levels were similar
among case and comparison participants. We did not find these pesticides
elevated in environmental samples, and we have no evidence that exposure
is from a common environmental source.

Similarly, we found DDE in biologic samples but have no evidence of an
ongoing source of exposure to DDT or DDE. DDT is a chlorinated organic
pesticide that was banned from most use in the United States in 1972 but
continues to be used internationally for mosquito control. These
chemicals persist in the environment and may accumulate in adipose
tissue, with levels persisting for decades. DDT and DDE are reasonably
expected to be human carcinogens based upon evidence from animal
studies; however, human studies are mixed and inconclusive with regard
to an association between DDT and DDE exposure and breast cancer and
leukemia. (Longnecker 1997). Groups at increased risk for exposure to
DDT and DDE include adults and children who have lived in countries
where DDT is still used or have eaten food (including breast milk) that
contains DDE. Our results suggest that the increased exposure in our
study population may be at least partially attributed to historical
exposures. Although we found lower exposure levels among our case
population than among our comparison participants, we recognize that
people may respond differently to defined exposures.

The cause or causes of leukemia in children are not known. Environmental
contaminants that have been at least theoretically linked with some form
of cancer include metals (e.g., arsenic), VOCs (e.g., benzene),
nonpersistent pesticides (e.g., organophosphates), persistent pesticides
(e.g., DDT), and radiation. Among these, only benzene has been clearly
implicated as a cause of leukemia (Irons 1999). Nonetheless, we
evaluated all of these chemicals in biologic and environmental samples.
As described above, we found no evidence of ongoing human exposure to
benzene or other VOCs.

We also attempted to collect information that would benefit researchers
who are evaluating the population-mixing theory as a risk scenario for
cancer clusters. This theory originated among European scientists, who
noticed that leukemia often clustered in isolated rural communities
after a sudden influx of people into the community. The scientists
speculated that the immigrants could be introducing a variety of
different infectious agents into a susceptible rural community that
could trigger an unusual and rare reaction among a very small number of
children within the susceptible population (Kinlen 1990 and 1993). We
evaluated this possibility, but did not find any difference in markers
of infectious disease between case children and comparison children.

### Limitations

Several limitations should be considered in interpreting the national
and county level data. First, the comparison results from the *National
Exposure Report* represent the U.S. population as a whole, not the
people living in Churchill County, Nevada. People included in the
*National Exposure Report* were mostly people living in the eastern and
western suburban and urban regions of the United States. People in
Churchill County live in a rural area, rich in agriculture and mining.
This difference may account for the higher levels of some metals and
pesticides in blood and urine of Churchill County residents than in the
general U.S. population. In addition, the volume of blood available for
analysis in the *National Exposure Report* was significantly lower than
the amount collected in Churchill County; this resulted in a lower limit
of detection and increased sensitivity to detect chemicals in the blood
of Churchill County residents than people in the *National Exposure
Report*. The detection limits for PCBs and persistent pesticides were
substantially lower for Churchill County than for people in the
*National Exposure Report*. Finally, levels of metals, pesticides and
other substances detected in blood and urine do not necessarily indicate
a health risk. Blood and urine levels of most of these chemicals have
not been associated with health problems.

The case and control comparisons have at least three limitations: the
small number of case children, the cross-sectional nature of the
measurements taken, and the multiple comparisons that were examined. In
most etiologic studies of ALL, proper study design would call for more
than 100 case children to provide study power sufficient to detect a
significant difference in risk for exposure between cases and
comparisons. The best studies enroll several hundred case-patients. In a
study of a cluster, however, the investigation is limited to the
children in the cluster itself. Unless some risk factor is particularly
unique to the children in the cluster, it will be very difficult to
identify. All of the chemicals measured in blood and urine and those
measured in the soil, air, water, and dust of the homes came from
samples collected after the cancer diagnosis. If a chemical caused the
child's cancer, the exposure would have to have occurred several months,
and possibly years, before the child's diagnosis. The Churchill County
results may (or may not) represent earlier exposures. Nonetheless, the
results provide reassuring information about the status of environmental
exposures in Churchill County.

Because the study collected information on 108 biologic measurements,
207 environmental measurements, and 6 infectious diseases and analyzed
these using different case definitions, thousands of comparisons were
made. As a result, we would expect to find several statistically
significant results due to chance alone. Thus, each significant finding
should be interpreted with an appreciation for biologic plausibility and
pre-existing hypotheses. Simply reporting a statistically significant
result is not sufficient to establish a cause and effect relation
between exposure and disease.

# CONCLUSIONS AND RECOMMENDATIONS

This investigation identified an ongoing environmental exposure of
concern among Churchill County residents. We confirmed that many people
living in Churchill County still receive significant arsenic exposure,
despite the general knowledge that Churchill County water exceeded
recommended levels of arsenic in drinking water
([http://www.cityoffallon.com/]{.underline}). New water treatment
facilities will increase the availability of arsenic-free drinking water
in this community. Until these new facilities are finished, we recommend
that the City of Fallon continue to educate the community about
alternative sources of drinking water.

Biologic results also identified tungsten as a potentially unique
exposure within Churchill County. Efforts are under way to further
define tungsten exposure in Nevada and to evaluate potential routes of
exposure. The results of this continued tungsten investigation will be
shared with the Churchill County community. Tungsten also is being
considered by the National Institutes of Health as a priority chemical
for toxicologic research.

Although biologic results demonstrated a limited degree of elevated
pesticide exposure in the community, environmental testing did not
identify any sources of ongoing exposure. We recommend conservative use
of personal household pesticides and recommend that state public health
officials increase public education efforts about safe use of
pesticides.

With the input of the Children's Oncology Group and other experts, we
plan to conduct genetic testing to try to determine whether differences
exist between case families and comparison families in genes that are
responsible for the way the elevated levels of environmental chemicals
we found are metabolized or the way environmental chemicals may affect
the products of genes. This means that we will look at normal genetic
variation among people that may make some people slightly more
susceptible than others to exposures. Little is known about genetic
variation among people at this time, and we do not expect the Fallon
study alone to provide definitive evidence. However, we believe that,
over time, this information will help us to understand how genes and the
environment act together to cause disease. The results of these analyses
will not predict sensitivity or vulnerability in an individual child,
but they will help us generate hypotheses about genetic differences in
individual responses to environmental contaminants.

All participants have been given their personal results and information
about how to minimize their environmental exposures. We encourage
participants to share any elevated findings with their personal
healthcare providers.

When we began this investigation, we recognized that our findings about
the relation between environmental exposures and cancer occurrence would
be limited by the small number of case reports, and we shared this
limitation with the Churchill County community. Nonetheless, we launched
and completed a multi-agency investigation that collected extensive
lifestyle information and used state-of-the-art laboratory analysis for
biomarkers of exposure. The data were carefully collected and analyzed.
Even though we did not discover an environmental exposure that explains
the cluster of leukemia in children in Churchill County, we collected
information and laboratory samples with rigor, and we envision that our
analytic results and stored biologic samples may be useful in any future
aggregation of data among similar occurrences of leukemia. CDC is
working with state health departments to review existing cancer cluster
investigation plans, as well as reviewing benefits and limitations of
conducting investigations. The results of the Churchill County
investigation will be used to identify ways we can collaborate to
increase our knowledge about environmental exposures and cancer
occurrence.

Table 1.\
Participants Enrolled in the Churchill County Study of Environmental
Chemicals

  ---------------------------------------- -------- ---------- ---------- ----------
  **Participants**                         **\#**   **Urine    **Blood    **%
                                                    sample**   sample**   Female**

  Case children alive at time of study     13       12         13         54%
  enrollment (Note: 1 case child was                                      
  deceased at time of case family                                         
  enrollment. Study includes 14 case                                      
  families.)                                                              

  Siblings of case children                15       15         14         34%

  Case parents and guardians               24       24         24         50%

  Other adults living with the case family 1        1          1          100%

  Comparison children who had a matched    47       46         47         40%
  case child                                                              

  Comparison children with no matched case 8        8          8          50%
  child                                                                   

  Comparison parents and guardians         92       92         92         55%

  Other adults living with the comparison  5        5          5          60%
  family                                                                  

  Total study population                   205      203        204        54%
  ---------------------------------------- -------- ---------- ---------- ----------

[]{#Table_2 .anchor}Table 2.\
Levels of Metals^a^ (μg/L)^b^ in Urine and Blood of People Living in the
United States and People Living in Churchill County, Nevada

+-----------+-------------+------------+------------+------+---------+
| **Metal** | **United    |            | *          |      | **Compa |
|           | States^c^** |            | *Churchill |      | rison** |
|           |             |            | County**   |      |         |
+-----------+-------------+------------+------------+------+---------+
|           | **Geometric | **95^th^   | *          | **%  |         |
|           | Mean**      | Pe         | *Geometric | \>   |         |
|           |             | rcentile** | Mean**     | U.S. |         |
|           | **(95%      |            |            | 95   |         |
|           | Confidence  |            | **(95%     | ^th^ |         |
|           | Int         |            | Confidence | or   |         |
|           | erval)^d^** |            | I          | He   |         |
|           |             |            | nterval)** | alth |         |
|           |             |            |            | Val  |         |
|           |             |            |            | ue** |         |
+-----------+-------------+------------+------------+------+---------+
| **A       | 0.11        | 0.41       | 0.15       | 4.4  | H^e^    |
| ntimony** | (           | (0         | (0         |      |         |
|           | 0.10--0.13) | .39--0.46) | .14--0.16) |      |         |
+-----------+-------------+------------+------------+------+---------+
| **        | NA^f^       | 50.0^g^    | 34.61      | 34.  | H       |
| Arsenic** |             |            | (28.       | 0^g^ |         |
|           |             |            | 07--42.68) |      |         |
+-----------+-------------+------------+------------+------+---------+
| *         | 1.15        | 6.60       | 2.45       | 14.3 | H       |
| *Barium** | (           | (          | (2         |      |         |
|           | 0.96--1.38) | 6.0--8.30) | .10--2.85) |      |         |
+-----------+-------------+------------+------------+------+---------+
| **Cadmium | 0.33        | 2.0^h^     | 0.31       | 0.0  | ^---i^  |
| (urine)** | (           |            | (0         |      |         |
|           | 0.31--0.35) |            | .28--0.34) |      |         |
+-----------+-------------+------------+------------+------+---------+
| **Cadmium | 0.41        | 5.0^h^     | NC^j^      | 0.0  | L^k^    |
| (blood)** | (           |            |            |      |         |
|           | 0.39--0.44) |            |            |      |         |
+-----------+-------------+------------+------------+------+---------+
| *         | 4.34        | 11.40      | 5.98       | 11.8 | H       |
| *Cesium** | (           | (10.       | (5         |      |         |
|           | 4.06--4.63) | 30--12.50) | .43--6.58) |      |         |
+-----------+-------------+------------+------------+------+---------+
| **C       | NA          | NA         | NC         | NA   | NA      |
| hromium** |             |            |            |      |         |
+-----------+-------------+------------+------------+------+---------+
| *         | 0.37        | 1.32       | 0.56       | 7.4  | H       |
| *Cobalt** | (           | (1         | (0         |      |         |
|           | 0.35--0.40) | .16--1.45) | .50--0.62) |      |         |
+-----------+-------------+------------+------------+------+---------+
| **Lead    | 0.76        | 25.0^h^    | 0.68       | 0.0  | ---     |
| (urine)** | (           |            | (0         |      |         |
|           | 0.71--0.81) |            | .61--0.76) |      |         |
+-----------+-------------+------------+------------+------+---------+
| **Lead    | 1.66        | 10.0^g^    | 1.11       | 0.0  | L       |
| (blood)** | (           |            | (1         |      |         |
|           | 1.58--1.73) |            | .02--1.21) |      |         |
+-----------+-------------+------------+------------+------+---------+
| **Ma      | NA          | NA         | 0.73       | NA   | NA      |
| nganese** |             |            | (0         |      |         |
|           |             |            | .67--0.80) |      |         |
+-----------+-------------+------------+------------+------+---------+
| **Mercury | 0.72        | 20.0^g^    | 0.38       | 0.0  | L       |
| (urine)** | (           |            | (0         |      |         |
|           | 0.64--0.81) |            | .32--0.44) |      |         |
+-----------+-------------+------------+------------+------+---------+
| **Mercury | 0.34        | 10.0^g^    | 0.32       | 0.0  | ---     |
| (blood)** | (           |            | (0         |      |         |
|           | 0.30--0.39) |            | .22--0.45) | 0.0  |         |
|           | 1-5 yrs     |            |            |      |         |
|           |             |            | 0.76       |      |         |
|           | 1.02        |            | (0         |      |         |
|           | (           |            | .65--0.88) |      |         |
|           | 0.81--1.22) |            |            |      |         |
|           | 16-49 yrs   |            |            |      |         |
+-----------+-------------+------------+------------+------+---------+
| **Mol     | 34.3        | 174 (153-- | 62.14      | 9.9  | H       |
| ybdenum** | (           | 201)       | (53.       |      |         |
|           | 29.4--40.1) |            | 52--72.15) |      |         |
+-----------+-------------+------------+------------+------+---------+
| *         | NA          | 5.0^l^     | NC         | 3.5  | L       |
| *Nickel** |             |            |            |      |         |
+-----------+-------------+------------+------------+------+---------+
| *         | NA          | 179.0^m^   | 121.02     | 0.0  | L       |
| *Selenium |             |            |            |      |         |
| (serum)** |             |            | (118.5     |      |         |
|           |             |            | 6--123.50) |      |         |
+-----------+-------------+------------+------------+------+---------+
| **T       | 0.17        | 0.45       | 0.16       | 2.0  | ---     |
| hallium** | (           | (0         | (0         |      |         |
|           | 0.16--0.18) | .42--0.47) | .15--0.18) |      |         |
+-----------+-------------+------------+------------+------+---------+
| **T       | 0.08        | 0.48       | 1.19       | 68.5 | H       |
| ungsten** | (           | (0         | (0         |      |         |
|           | 0.07--0.09) | .41--0.55) | .89--1.59) |      |         |
+-----------+-------------+------------+------------+------+---------+
| **        | 0.007       | 0.05       | 0.02       | 23.7 | H       |
| Uranium** | (0.         | (0         | (0         |      |         |
|           | 006--0.008) | .04--0.05) | .02--0.03) |      |         |
+-----------+-------------+------------+------------+------+---------+

> a Urine levels are noncreatinine adjusted. Blood levels are not
> lipid-adjusted.
>
> b Micrograms per liter
>
> c U.S. values are from the *Second National Report on Human Exposure
> to Environmental Chemicals,* 2003.
>
> d The interval of numbers in which we are 95% assured the value is
> contained.
>
> e The lower boundary of the Churchill County confidence interval (CI)
> was higher than the upper boundary of the CI for the U.S. level or, b)
> more than 10% of the Churchill County participants had a value above
> the U.S. 95^th^ percentile.
>
> f Not available. This metal was not included in the *Second National
> Report on Human Exposure to Environmental Chemicals*, 2003.
>
> g Goldfrank L. Goldfrank's Toxicologic Emergencies 7th ed. 2002.
> McGraw Hill; New York and Haddad L, Shannon M, Winchester J. Haddad's
> Clinical Management of Poisoning and Drug Overdose. 3^rd^ ed. 1998. WB
> Saunders Company; Philadelphia.
>
> h Lauwerys R, Hoet P. In Industrial Chemical Exposure: Guidelines for
> Biological Monitoring 3rd ed. 2001. Lewis Publishers; Boca Raton,
> Florida.
>
> i The Churchill County geometric mean is consistent with national
> estimates.
>
> j Not Calculated was used when less than 60% of the study population
> had detectable levels of this chemical.
>
> k The upper boundary of the Churchill County CI was below the lower
> boundary of the CI for the U.S. level and b) less then 10% of the
> Churchill County participants had a value above the U.S. 95^th^
> percentile.
>
> l White M, Sabbioni E. Trace element reference values in tissues from
> inhabitants of the European Union. Sci Total Environ 1998;216:253-70.
>
> m Hogberg, J. Selenium. In Handbook on the Toxicology of Metals. 2nd
> ed.; 1986.

Table 3.\
Estimated Risk for Childhood Leukemia Associated with Urine and Blood
Levels of Metals (μg/L)^\*^ for Case Children and Families Compared with
Control Children and Families Living in Churchill County

+------------------+-----------------+---------+-----------+---------+
|                  | **Case vs.      |         | **Case    |         |
|                  | Comparison      |         | vs.       |         |
|                  | (Child)**       |         | C         |         |
|                  |                 |         | omparison |         |
|                  |                 |         | (Famil    |         |
|                  |                 |         | ies)^†^** |         |
+------------------+-----------------+---------+-----------+---------+
| **Metal**        | **Odds          | **      | **Odds    | ***P*-  |
|                  | Ratio^‡^**      | *P*-Val | Ratio**   | Value** |
|                  |                 | ue^§^** |           |         |
+------------------+-----------------+---------+-----------+---------+
| **Antimony**     | 1.40            | 0.31    | 0.80      | 0.36    |
+------------------+-----------------+---------+-----------+---------+
| **Arsenic**      | 0.60            | 0.22    | 0.67      | 0.11    |
+------------------+-----------------+---------+-----------+---------+
| **Barium**       | 0.91            | 0.77    | 0.86      | 0.52    |
+------------------+-----------------+---------+-----------+---------+
| **Cesium**       | 0.64            | 0.25    | 0.74      | 0.20    |
+------------------+-----------------+---------+-----------+---------+
| **Cobalt**       | 0.84            | 0.68    | 1.18      | 0.45    |
+------------------+-----------------+---------+-----------+---------+
| **Lead (urine)** | 0.64            | 0.24    | 0.98      | 0.93    |
|                  |                 |         |           |         |
| **               |                 |         |           |         |
| (**μ**g/dL)**^║^ |                 |         |           |         |
+------------------+-----------------+---------+-----------+---------+
| **Lead (blood)** | 0.33            | 0.002   | 1.24      | 0.36    |
|                  |                 |         |           |         |
| **               |                 |         |           |         |
| (**μ**g/dL)**^║^ |                 |         |           |         |
+------------------+-----------------+---------+-----------+---------+
| **Manganese**    | 1.51            | 0.30    | 0.96      | 0.84    |
+------------------+-----------------+---------+-----------+---------+
| **Mercury        | 0.84            | 0.66    | 0.89      | 1.03    |
| (urine)**        |                 |         |           |         |
+------------------+-----------------+---------+-----------+---------+
| **Mercury        | 1.15            | 0.68    | 1.50      | 0.14    |
| (blood)**        |                 |         |           |         |
+------------------+-----------------+---------+-----------+---------+
| **Molybdenum**   | 0.82            | 0.64    | 0.77      | 0.27    |
+------------------+-----------------+---------+-----------+---------+
| **Selenium       | 0.75            | 0.42    | 0.84      | 0.48    |
| (serum)**        |                 |         |           |         |
+------------------+-----------------+---------+-----------+---------+
| **Thallium**     | 0.68            | 0.35    | 0.80      | 0.34    |
+------------------+-----------------+---------+-----------+---------+
| **Tungsten**     | 0.78            | 0.57    | 1.06      | 0.82    |
+------------------+-----------------+---------+-----------+---------+
| **Uranium**      | 1.00            | NC^¶^   | 1.11      | 0.62    |
+------------------+-----------------+---------+-----------+---------+

> **\*** Micrograms per liter
>
> † Family members include parents/guardians only.
>
> ‡ The odds ratio is the estimated relative risk of leukemia associated
> with one standard error of the geometric mean increase in the blood or
> urine level of each chemical. Odds ratios are not reported if fewer
> than 60% of cases and controls had detectable levels of the chemical
> in their blood or urine.
>
> § The *P*-value is from likelihood ratio test. The *P*-value estimates
> the probability that the deviation of the odds ratio from 1.0 (no
> difference in risk) is due to chance. A *P*-value less than 0.05
> suggests that chance is unlikely to explain the deviation.
>
> ^║^ Micrograms per deciliter
>
> ¶ *P*-value from the likelihood ratio test could not be calculated.
>
> **Metals that were analyzed in the Churchill County investigation but
> that were detected in fewer than 60% of the participants were:**
>
> Cadmium
>
> Nickel
>
> Chromium

[]{#Table_4 .anchor}**Table 4.\
Nonpersistent Pesticide Levels\* (μg/L)† in Urine of People Living in
the United States and People Living in Churchill County, Nevada**

+--------------+-----------+---------+-----------+---------+--------+
| N            | United    |         | Churchill |         | Comp   |
| onpersistent | States    |         | County    |         | arison |
| Pesticide or |           |         |           |         |        |
| Metabolite   |           |         |           |         |        |
+--------------+-----------+---------+-----------+---------+--------+
|              | Geometric | 95^th^  | Geometric | \%      |        |
|              | Mean      | Per     | Mean      | \>U.S.  |        |
|              |           | centile |           |         |        |
|              | (95%      |         | (95%      | 95^th^  |        |
|              | C         |         | C         | per     |        |
|              | onfidence |         | onfidence | centile |        |
|              | Int       |         | Interval) |         |        |
|              | erval)^‡^ |         |           |         |        |
+--------------+-----------+---------+-----------+---------+--------+
| 1-Naphthol   | 1.70      | 12.0    | NC^§^     | 7.9     | L^║^   |
|              | (1.       | (7.20   |           |         |        |
|              | 38--2.09) | --19.0) |           |         |        |
+--------------+-----------+---------+-----------+---------+--------+
| Methyl       | NC        | 5.0     | NC        | 9.9     | ---^¶^ |
| parathion    |           | (3.3    |           |         |        |
|              |           | 0--9.0) |           |         |        |
+--------------+-----------+---------+-----------+---------+--------+
| Acephate     | NA^\#^    | NA      | NC        | ---     | ---    |
+--------------+-----------+---------+-----------+---------+--------+
| Azinophos    | NA        | NA      | NC        | ---     | ---    |
+--------------+-----------+---------+-----------+---------+--------+
| Carb         | NC        | 0.74    | NC        | 0.5     | ---    |
| ofuranphenol |           | (NC     |           |         |        |
|              |           | --1.30) |           |         |        |
+--------------+-----------+---------+-----------+---------+--------+
| Chlorpyrifos | 1.77      | 9.90    | 2.46      | 16.3    | H      |
|              | (1.       | (7.60   | (1.       |         | ^\*\*^ |
|              | 56--2.01) | --14.0) | 93--3.14) |         |        |
+--------------+-----------+---------+-----------+---------+--------+
| Coumaphos    | NA        | NA      | NC        | ---     | ---    |
+--------------+-----------+---------+-----------+---------+--------+
| Diazinon     | NC        | NC      | NC        | ---     | ---    |
+--------------+-----------+---------+-----------+---------+--------+
| Diethyldit   | NC        | 0.87    | NC        | 9.5     | ---    |
| hiophosphate |           | (0.6    |           |         |        |
|              |           | 5--1.0) |           |         |        |
+--------------+-----------+---------+-----------+---------+--------+
| Diet         | 1.03      | 13.0    | NC        | 4.0     | L      |
| hylphosphate | (0.       | (8.00   |           |         |        |
|              | 76--1.40) | --21.0) |           |         |        |
+--------------+-----------+---------+-----------+---------+--------+
| Diethylt     | NC        | 2.20    | 1.04      | 29.5    | H      |
| hiophosphate |           | (1.70   | (0.       |         |        |
|              |           | --2.80) | 81--1.33) |         |        |
+--------------+-----------+---------+-----------+---------+--------+
| Dimethyldit  | NC        | 19.0    | NC        | 3.7     | ---    |
| hiophosphate |           | (17.0   |           |         |        |
|              |           | --37.0) |           |         |        |
+--------------+-----------+---------+-----------+---------+--------+
| Dimet        | NC        | 13.0    | NC        | 8.5     | ---    |
| hylphosphate |           | (9.50   |           |         |        |
|              |           | --21.0) |           |         |        |
+--------------+-----------+---------+-----------+---------+--------+
| Dimethylt    | 1.82      | 46.0    | NC        | 7.5     | L      |
| hiophosphate | (1.       | (38.0   |           |         |        |
|              | 43--2.32) | --60.0) |           |         |        |
+--------------+-----------+---------+-----------+---------+--------+
| Isazophos    | NA        | NA      | NC        | ---     | ---    |
+--------------+-----------+---------+-----------+---------+--------+
| Malathion    | NC        | NC      | NC        | ---     | ---    |
+--------------+-----------+---------+-----------+---------+--------+
| M            | NA        | NA      | NC        | ---     | ---    |
| ethamidophos |           |         |           |         |        |
+--------------+-----------+---------+-----------+---------+--------+
| Pirimiphos   | NA        | NA      | NC        | ---     | ---    |
+--------------+-----------+---------+-----------+---------+--------+
| Propoxur     | NC        | NC      | NC        | ---     | ---    |
+--------------+-----------+---------+-----------+---------+--------+
| 2,4-Di       | 1.11      | 22.0    | 1.15      | 0.5     | ---    |
| chlorophenol | (0.       | (17.0   | (0.       |         |        |
|              | 88--1.40) | --31.0) | 91--1.46) |         |        |
+--------------+-----------+---------+-----------+---------+--------+
| 2,4,5-Tri    | NC        | 16.0    | 4.48      | 20.3    | H      |
| chlorophenol |           | (4.30   | (3.       |         |        |
|              |           | --39.0) | 64--5.53) |         |        |
+--------------+-----------+---------+-----------+---------+--------+
| 2,4,6-Tri    | 2.85      | 25.0    | NC        | 17.3    | H      |
| chlorophenol | (2.       | (17.0   |           |         |        |
|              | 58--3.15) | --37.0) |           |         |        |
+--------------+-----------+---------+-----------+---------+--------+
| Penta        | NC        | 1.30    | NC        | 4.5     | ---    |
| chlorophenol |           | (0.6    |           |         |        |
|              |           | 6--2.0) |           |         |        |
+--------------+-----------+---------+-----------+---------+--------+
| 2,4-D        | NC        | NC      | NC        | ---     | ---    |
+--------------+-----------+---------+-----------+---------+--------+
| 2,4,5-T      | NC        | NC      | NC        | ---     | ---    |
+--------------+-----------+---------+-----------+---------+--------+
| Atrazine     | NC        | NC      | NC        | ---     | ---    |
+--------------+-----------+---------+-----------+---------+--------+
| 3-Ph         | NA        | NA      | NC        | ---     | ---    |
| enoxybenzoic |           |         |           |         |        |
| acid         |           |         |           |         |        |
+--------------+-----------+---------+-----------+---------+--------+
| o-           | 0.49      | 2.0     | NC        | 17.8    | H      |
| Phenylphenol | (0.       | (1.60   |           |         |        |
|              | 41--0.59) | --2.50) |           |         |        |
+--------------+-----------+---------+-----------+---------+--------+
| DEET         | NC        | NC      | NC        | ---     | ---    |
+--------------+-----------+---------+-----------+---------+--------+
| 2,5-Di       | 6.01      | 440     | NC        | 0.0     | L      |
| chlorophenol | (4.       | (24     |           |         |        |
|              | 22--8.57) | 0--700) |           |         |        |
+--------------+-----------+---------+-----------+---------+--------+
| 2-Naphthol   | 0.47      | 15.0    | 0.98      | 8.4     | H      |
|              | (0.       | (9.90   | (0.       |         |        |
|              | 33--0.68) | --19.3) | 73--1.32) |         |        |
+--------------+-----------+---------+-----------+---------+--------+

**\*** Urine levels are noncreatinine adjusted. Blood levels are not
lipid-adjusted.

† Micrograms per liter

‡ The interval of numbers in which we are 95% assured the value is
contained.

§ Not Calculated was used when less than 60% of the study population had
detectable levels of this chemical

^║^[]{.mark} The upper boundary of the Churchill County CI was below
the lower boundary of the CI for the U.S. level and b) less then 10% of
the Churchill County participants had a value above the U.S. 95^th^
percentile.

^¶^ The Churchill County geometric mean is consistent with national
estimates.

**\#** Not available. This pesticide was not included in the *Second
National Report on Human Exposure to Environmental Chemicals*, 2003.

**\*\*** The lower boundary of the Churchill County confidence interval
(CI) was higher than the upper boundary of the CI for the U.S. level or,
b) more than 10% of the Churchill County participants had a value above
the U.S. 95^th^ percentile.

[]{#Table_5 .anchor}Table 5\
The Estimated Risk of Childhood Leukemia Associated with Urine Levels of
Nonpersistent Pesticides for Case Children and Families Compared with
Control Children and Families Living in Churchill County

  -----------------------------------------------------------------------------------------
                              **Case vs.                 **Case vs.         
                              Comparison                 Comparison         
                              (Child)**                  (Families)^\*^**   
  --------------------------- ------------ ------------- ------------------ ---------------
  **Nonpersistent Pesticide   **Odds       ***P*-Value   **Odds Ratio**     ***P*-Value**
  or Metabolite ^†^**         Ratio^‡^**   ^§^**                            

  **1-Naphthol**              0.84         0.62          NC^║^              NC

  **Chlorpyrifos**            0.78         0.51          1.05               0.82

  **Diethylthiophosphate**    0.91         0.79          0.88               0.59

  **2,4-Dichlorophenol**      0.88         0.70          0.90               0.68

  **2,4,5-Trichlorophenol**   0.57         0.09          1.31               0.24

  **2,4,6-Trichlorophenol**   0.91         0.77          NC                 NC

  **2-Naphthol**              1.34         0.50          0.98               0.93
  -----------------------------------------------------------------------------------------

> \* Family members include parents/guardians only.
>
> **^†^** A breakdown product of another chemical.
>
> **^‡^** The estimated relative risk of leukemia associated with one
> standard error of the geometric mean increase in the blood or urine
> level of each chemical. Odds ratios are not reported if fewer than 60%
> of cases and controls had detectable levels of the chemical in their
> blood or urine.
>
> **^§^** Estimates the probability that the deviation of the odds ratio
> from 1.0 (no difference in risk) is due to chance. A *P*-value less
> than 0.05 suggests that chance is unlikely to explain the deviation.
>
> NC^║^ Not Calculated was used when less than 60% of the study
> population had detectable levels of this chemical.
>
> **Nonpersistent pesticides that were analyzed in the Churchill County
> investigation but that were detected in fewer than 60% of the
> participants were:**
>
> 2,4-D 2,4,5-T Propoxur
>
> 2,5-Dichlorophenol o-Phenyl phenol Pentachlorophenol
>
> 3-Phenoxybenzoic acid Parathion/methyl parathion Pirimiphos
>
> Acephate Methamidophos Isazophos
>
> Atrazine Coumaphos Malathion
>
> Azinophos DEET Diazinon
>
> Carbofuranphenol Diethylphosphate Diethyldithiophosphate
>
> Dimethyldithiophosphate Dimethylphosphate Dimethylthiophosphate

[]{#Table_6a .anchor}Table 6a.\
Persistent Pesticide Levels^\*^ (ng/g lipid)^†^ in Blood of People
Living in the United States and People Living in Churchill County,
Nevada

+-------------+-----------+-----------+------------+--------+--------+
| **          | **United  |           | *          |        | **     |
| Pesticide** | States**  |           | *Churchill |        | Compar |
|             |           |           | County**   |        | ison** |
+-------------+-----------+-----------+------------+--------+--------+
|             | **        | **95^th^  | *          | **%    |        |
|             | Geometric | P         | *Geometric | Above  |        |
|             | Mean**    | ercentile | Mean**     | 95^th^ |        |
|             |           | *National |            | Percen |        |
|             | **        | Exposure  | **Total    | tile** |        |
|             | *National | Report*** | Study      |        |        |
|             | Exposure  |           | Po         |        |        |
|             | Report*   |           | pulation** |        |        |
|             | (C        |           | **(        |        |        |
|             | onfidence |           | Confidence |        |        |
|             | Inter     |           | I          |        |        |
|             | val)^‡^** |           | nterval)** |        |        |
+-------------+-----------+-----------+------------+--------+--------+
| **DDE, p,   | 260.0     | 1780      | 447.07     | 6.9    | H*     |
| p, -**      | (23       | (15       | (355.0     |        | *^§^** |
|             | 4--289.0) | 20--2230) | 9--562.87) |        |        |
+-------------+-----------+-----------+------------+--------+--------+
| **DDT, o,   | NC^║^     | NC        | NC         | 0.0    | ---^¶^ |
| p, -**      |           |           |            |        |        |
+-------------+-----------+-----------+------------+--------+--------+
| **DDT, p,   | NC        | 27.0      | NC         | 3.0    | ---    |
| p, -**      |           | (         |            |        |        |
|             |           | NC--34.0) |            |        |        |
+-------------+-----------+-----------+------------+--------+--------+
| *           | N         | NA        | NC         | NA     | ---    |
| *Dieldrin** | A**^\#^** |           |            |        |        |
+-------------+-----------+-----------+------------+--------+--------+
| *           | NC        | 24.1      | NC         | 1.0    | ---    |
| *Heptachlor |           | (16       |            |        |        |
| epoxide**   |           | .9--35.5) |            |        |        |
+-------------+-----------+-----------+------------+--------+--------+
| **Hexachlo  | NC        | NC        | 10.46      | 0.0    | ---    |
| robenzene** |           |           | (8.        |        |        |
|             |           |           | 34--13.10) |        |        |
+-------------+-----------+-----------+------------+--------+--------+
| **H         | 15.00     | 111.0     | NC         | 2.0    | ---    |
| exachloro-c | (         | (88.      |            |        |        |
| yclohexane, | NC-16.10) | 2--137.0) |            |        |        |
| beta**      |           |           |            |        |        |
+-------------+-----------+-----------+------------+--------+--------+
| **H         | NC        | NC        | NC         | 0.0    | ---    |
| exachloro-c |           |           |            |        |        |
| yclohexane, |           |           |            |        |        |
| gamma**     |           |           |            |        |        |
+-------------+-----------+-----------+------------+--------+--------+
| **Mirex**   | NC        | NC        | NC         | 0.0    | ---    |
+-------------+-----------+-----------+------------+--------+--------+
| **Oxy       | NC        | 44.8      | NC         | 0.0    | ---    |
| chlordane** |           | (41       |            |        |        |
|             |           | .4--49.6) |            |        |        |
+-------------+-----------+-----------+------------+--------+--------+
| **Trans     | 18.3      | 77.1      | 2.66       | 1.0    | L**^\  |
| nonachlor** | (16       | (65       | (1         |        | *\*^** |
|             | .9--19.7) | .9--84.6) | .65--4.29) |        |        |
+-------------+-----------+-----------+------------+--------+--------+

**\*** Levels have been lipid-adjusted.

-   Nanograms per gram lipid

```{=html}
<!-- -->
```
-   The interval of numbers in which we are 95% assured the value is
    contained.

```{=html}
<!-- -->
```
-   The lower boundary of the Churchill County confidence interval (CI)
    was higher than the upper boundary of the CI for the U.S. level
    or, b) more than 10% of the Churchill County participants had a
    value above the U.S. 95^th^ percentile.

^║^ Not Calculated was used when less than 60% of the study population
had detectable levels of this chemical.

^¶^ The Churchill County geometric mean is consistent with national
estimates.

**\#** Not available. This pesticide was not included in the *Second
National Report on Human Exposure to Environmental Chemicals*, 2003.

**\*\*** The upper boundary of the Churchill County CI was below the
lower boundary of the CI for the U.S. level and b) less then 10% of the
Churchill County participants had a value above the U.S. 95^th^
percentile.

[]{#Table_6b .anchor}Table 6b.\
Polychlorinated Biphenyl^\*^ Levels (ng/g lipid)^†^ in Blood of People
Living in the United States and People Living in Churchill County,
Nevada

+----+------------+--------------+-------------+----------+-----------+
| *  | **United   |              | **Churchill |          | **Com     |
| *P | States**   |              | County**    |          | parison** |
| CB |            |              |             |          |           |
| ** |            |              |             |          |           |
+----+------------+--------------+-------------+----------+-----------+
|    | *          | **95^th^     | **Geometric | **%      |           |
|    | *Geometric | Percentile   | Mean**      | above    |           |
|    | Mean**     | from         |             | 95^th^   |           |
|    |            | *National    | **Total     | Perc     |           |
|    | *          | Exposure     | Study       | entile** |           |
|    | **National | Report***    | Population  |          |           |
|    | Exposure   |              | (Confidence |          |           |
|    | Report*    |              | Interval)** |          |           |
|    | (          |              |             |          |           |
|    | Confidence |              |             |          |           |
|    | Inte       |              |             |          |           |
|    | rval)**^‡^ |              |             |          |           |
+----+------------+--------------+-------------+----------+-----------+
| ** | NC^§^      | NC           | 2.63        | --       | --^║^     |
| 18 |            |              | (           |          |           |
| ** |            |              | 2.13--3.25) |          |           |
+----+------------+--------------+-------------+----------+-----------+
| ** | NC         | NC           | 5.84        | --       | --        |
| 28 |            |              | (           |          |           |
| ** |            |              | 5.31--6.41) |          |           |
+----+------------+--------------+-------------+----------+-----------+
| ** | NC         | NC           | 0.08        | --       | --        |
| 44 |            |              | (           |          |           |
| ** |            |              | 0.04--0.16) |          |           |
+----+------------+--------------+-------------+----------+-----------+
| ** | NC         | NC           | 1.00        | --       | --        |
| 49 |            |              | (           |          |           |
| ** |            |              | 0.72--1.40) |          |           |
+----+------------+--------------+-------------+----------+-----------+
| ** | NC         | NC           | 1.99        | --       | --        |
| 52 |            |              | (           |          |           |
| ** |            |              | 1.78--2.23) |          |           |
+----+------------+--------------+-------------+----------+-----------+
| ** | NC         | NC           | 0.38        | --       | --        |
| 66 |            |              | (           |          |           |
| ** |            |              | 0.22--0.63) |          |           |
+----+------------+--------------+-------------+----------+-----------+
| ** | NC         | 29.0         | 3.29        | 0.49     | --        |
| 74 |            | (25.0--32.1) | (           |          |           |
| ** |            |              | 2.64--4.11) |          |           |
+----+------------+--------------+-------------+----------+-----------+
| ** | NC         | NC           | NC          | --       | --        |
| 87 |            |              |             |          |           |
| ** |            |              |             |          |           |
+----+------------+--------------+-------------+----------+-----------+
| ** | NC         | 18.6         | 2.11        | 0.0      | --        |
| 99 |            | (15.5--21.1) | (           |          |           |
| ** |            |              | 1.71--2.60) |          |           |
+----+------------+--------------+-------------+----------+-----------+
| *  | NC         | NC           | 1.05        | --       | --        |
| *1 |            |              | (           |          |           |
| 01 |            |              | 0.80--1.38) |          |           |
| ** |            |              |             |          |           |
+----+------------+--------------+-------------+----------+-----------+
| *  | NC         | NC           | NC          | --       | --        |
| *1 |            |              |             |          |           |
| 05 |            |              |             |          |           |
| ** |            |              |             |          |           |
+----+------------+--------------+-------------+----------+-----------+
| *  | NC         | NC           | 0.25        | --       | --        |
| *1 |            |              | (           |          |           |
| 10 |            |              | 0.15--0.40) |          |           |
| ** |            |              |             |          |           |
+----+------------+--------------+-------------+----------+-----------+
| *  | NC         | 42.4         | 3.75        | 0.0      | --        |
| *1 |            | (33.0--52.0) | (           |          |           |
| 18 |            |              | 3.27--4.30) |          |           |
| ** |            |              |             |          |           |
+----+------------+--------------+-------------+----------+-----------+
| *  | NC         | NC           | NC          | --       | --        |
| *1 |            |              |             |          |           |
| 28 |            |              |             |          |           |
| ** |            |              |             |          |           |
+----+------------+--------------+-------------+----------+-----------+
| *  | NC         | 70.5         | 2.86        | 0.0      | --        |
| *1 |            | (59.3--83.4) | (           |          |           |
| 38 |            |              | 2.03--4.05) |          |           |
| ** |            |              |             |          |           |
+----+------------+--------------+-------------+----------+-----------+
| *  | NC         | 13.1         | NC          | 1.0      | --        |
| *1 |            | (NC--14.9)   |             |          |           |
| 46 |            |              |             |          |           |
| ** |            |              |             |          |           |
+----+------------+--------------+-------------+----------+-----------+
| *  | NC         | NC           | 0.11        | --       | --        |
| *1 |            |              | (           |          |           |
| 49 |            |              | 0.06--0.21) |          |           |
| ** |            |              |             |          |           |
+----+------------+--------------+-------------+----------+-----------+
| *  | NC         | NC           | NC          | --       | --        |
| *1 |            |              |             |          |           |
| 51 |            |              |             |          |           |
| ** |            |              |             |          |           |
+----+------------+--------------+-------------+----------+-----------+
| *  | NC         | 111          | 11.91       | 0.0      | --        |
| *1 |            | (92.0--127)  | (10         |          |           |
| 53 |            |              | .24--13.85) |          |           |
| ** |            |              |             |          |           |
+----+------------+--------------+-------------+----------+-----------+
| *  | NC         | 16.5         | 0.16        | 0.0      | --        |
| *1 |            | (15.2--18.7) | (           |          |           |
| 56 |            |              | 0.10--0.27) |          |           |
| ** |            |              |             |          |           |
+----+------------+--------------+-------------+----------+-----------+
| *  | NC         | NC           | NC          | --       | --        |
| *1 |            |              |             |          |           |
| 57 |            |              |             |          |           |
| ** |            |              |             |          |           |
+----+------------+--------------+-------------+----------+-----------+
| *  | NC         | NC           | NC          | --       | --        |
| *1 |            |              |             |          |           |
| 67 |            |              |             |          |           |
| ** |            |              |             |          |           |
+----+------------+--------------+-------------+----------+-----------+
| *  | NC         | 30.8         | 0.69        | 1.0      | --        |
| *1 |            | (26.4--36.5) | (           |          |           |
| 70 |            |              | 0.42--1.14) |          |           |
| ** |            |              |             |          |           |
+----+------------+--------------+-------------+----------+-----------+
| *  | NC         | NC           | NC          | --       | --        |
| *1 |            |              |             |          |           |
| 72 |            |              |             |          |           |
| ** |            |              |             |          |           |
+----+------------+--------------+-------------+----------+-----------+
| *  | NC         | NC           | NC          | --       | --        |
| *1 |            |              |             |          |           |
| 77 |            |              |             |          |           |
| ** |            |              |             |          |           |
+----+------------+--------------+-------------+----------+-----------+
| *  | NC         | NC           | NC          | --       | --        |
| *1 |            |              |             |          |           |
| 78 |            |              |             |          |           |
| ** |            |              |             |          |           |
+----+------------+--------------+-------------+----------+-----------+
| *  | NC         | 79.0         | 5.26        | 2.0      | --        |
| *1 |            | (70.9--91.4) | (           |          |           |
| 80 |            |              | 3.74--7.39) |          |           |
| ** |            |              |             |          |           |
+----+------------+--------------+-------------+----------+-----------+
| *  | NC         | NC           | NC          | --       | --        |
| *1 |            |              |             |          |           |
| 83 |            |              |             |          |           |
| ** |            |              |             |          |           |
+----+------------+--------------+-------------+----------+-----------+
| *  | NC         | 24.3         | 0.49        | 1.0      | --        |
| *1 |            | (21.8--26.5) | (           |          |           |
| 87 |            |              | 0.30--0.81) |          |           |
| ** |            |              |             |          |           |
+----+------------+--------------+-------------+----------+-----------+
| *  | NC         | NC           | NC          | --       | --        |
| *1 |            |              |             |          |           |
| 89 |            |              | (., .)      |          |           |
| ** |            |              |             |          |           |
+----+------------+--------------+-------------+----------+-----------+
| *  | NC         | NC           | NC          | --       | --        |
| *1 |            |              |             |          |           |
| 94 |            |              | (., .)      |          |           |
| ** |            |              |             |          |           |
+----+------------+--------------+-------------+----------+-----------+
| *  | NC         | NC           | NC          | --       | --        |
| *1 |            |              |             |          |           |
| 95 |            |              |             |          |           |
| ** |            |              |             |          |           |
+----+------------+--------------+-------------+----------+-----------+
| *  | NC         | NC           | NC          | --       | --        |
| *1 |            |              |             |          |           |
| 96 |            |              | (., .)      |          |           |
| ** |            |              |             |          |           |
+----+------------+--------------+-------------+----------+-----------+
| *  | NC         | NC           | 0.18        | --       | --        |
| *2 |            |              | (           |          |           |
| 01 |            |              | 0.10--0.30) |          |           |
| ** |            |              |             |          |           |
|    |            |              | (0.009,     |          |           |
|    |            |              | 0.012)      |          |           |
+----+------------+--------------+-------------+----------+-----------+
| *  | NC         | NC           | NC          | --       | --        |
| *2 |            |              |             |          |           |
| 06 |            |              | (., .)      |          |           |
| ** |            |              |             |          |           |
+----+------------+--------------+-------------+----------+-----------+

> **\*** Polychlorinated Biphenyl (PCB)
>
> † Nanograms per gram lipid

-   The interval of numbers in which we are 95% assured the value is
    contained.

```{=html}
<!-- -->
```
-   Not Calculated was used when less than 60% of the study population
    had detectable levels of this chemical.

    ^║^ The Churchill County geometric mean is consistent with national
    estimates.

Table 7\
Risk Factors Potentially Associated with Exposure to\
DDT and DDE (ng/g lipid)

  ---------------- ---------------- ------------ --------------------- ------------------
  **Subset**       **Risk Factor**  **Median**   **Geometric Mean DDE  ***P*-value^‡^**
                                                 (95% CI)**            

  Study Children   Child born or    409.5        550.7 (171.7-1766.3)  0.27
                   resided outside                                     
                   of U.S. (n=7)                                       

                   Child born or    274.4        305.1 (253.5-367.3)   
                   living only in                                      
                   U.S. only (n=60)                                    

                   Child breast fed 541.8        1055.0 (275.6-4039.2) 0.06
                   by mother born                                      
                   outside U.S.                                        
                   (n=6)                                               

                   Child not breast 279.0        297.6 (250.0-354.3)   
                   fed, or breast                                      
                   fed by mother                                       
                   born in U.S.                                        
                   (n=56)                                              

  Biological       Mother born      2687.3       1889.5                0.10
  Mothers          outside U.S.                  (299.0-11941.6)       
                   (n=4)                                               

                   Mother born in   477.0        439.3 (272.0-709.4)   
                   U.S. (n=52)                                         

  Biological       Father born      964.5        823.1 (246.6-2747.5)  0.66
  Fathers          outside U.S.                                        
                   (n=5)                                               

                   Father born in   611.6        699.7 (554.1-883.6)   
                   U.S. (n=41)                                         
  ---------------- ---------------- ------------ --------------------- ------------------

‡ *P*-value from t-test for two-sample differences in means.

[]{#table_8a .anchor}Table 8a\
The Estimated Risk of Childhood Leukemia Associated with Blood Levels of
Persistent Pesticide Levels (ng/g lipid)^\*^ for Cases Compared with
Controls Living in Churchill County

  ----------------------------------------------------------------------------------------
                              **Case vs.                      **Case vs.   
                              Comparison                      Comparison   
                              (Child)**                       (Families    
                                                              )**^†^       
  --------------------------- ------------ ------------------ ------------ ---------------
  **Persistent Pesticide**    **Odds       ***P*-Value**^§^   **Odds       ***P*-Value**
                              Ratio** ^‡^                     Ratio**      

  **DDE, p,p,-**              0.53         0.26               0.79         0.25

  **Hexachlorobenzene**       0.70         0.06               1.35         0.52

  **Transnonachlor**          NC^║^        NC                 1.40         0.41

  **Hexachloro-cyclohexane,   NC           NC                 1.27         0.32
  beta**                                                                   

  **Oxychlordane**            NC           NC                 1.24         0.40
  ----------------------------------------------------------------------------------------

\* Nanogram per gram lipid

> † Family members include parents/guardians only.
>
> ‡ The odds ratio is the estimated relative risk of leukemia associated
> with one standard error of the geometric mean increase in the blood or
> urine level of each chemical. Odds ratios are not reported if fewer
> than 60% of cases and controls had detectable levels of the chemical
> in their blood or urine.
>
> § The *P*-value estimates the probability that the deviation of the
> odds ratio from 1.0 (no difference in risk) is due to chance. A
> *P*-value less than 0.05 suggests that chance is unlikely to explain
> the deviation.
>
> ^║^ Not calculated. Less than 60% of the study population had
> detectable levels of this chemical.
>
> **Persistent pesticides that were analyzed in the Churchill County
> investigation but that were detected in fewer than 60% of the
> participants were:**

DDT, o,p,- Mirex

> DDT, p,p,- Heptachlor epoxide

Dieldrin Hexachloro-cyclohexane, gamma

[]{#Table_8b .anchor}Table 8b.\
The Estimated Risk of Childhood Leukemia Associated with Blood Levels of
Polychlorinated Biphenyls (ng/g lipid)^\*^ for Case Children and
Families Compared with Control Children and Families Living in Churchill
County

  ----------------------------------------------------------------------------------
  **PCB**^‡^   **Case vs.                       **Case vs.        
               Comparison                       Comparison        
               (Child)**                        (Families)**^†^   
  ------------ ------------- ------------------ ----------------- ------------------
               **Odds        ***P*-Value**^║^   **Odds Ratio**    ***P*-Value**
               Ratio**^§^                                         

  **18**       9.1           0.002              2.98              0.02

  **28**       4.0           0.001              1.41              0.17

  **44**       NC^\*\*^      NC                 1.33              0.25

  **49**       71.23         \<0.001            1.59              0.13

  **52**       3.25          0.002              1.60              0.05

  **66**       1.30          0.46               1.37              0.22

  **74**       0.88          0.66               0.70              0.07

  **99**       0.73          0.09               1.99              0.17

  **101**      15.32         0.01               0.98              0.92

  **110**      0.73          0.28               0.91              0.69

  **118**      0.59          0.02               1.42              0.37

  **138**      0.76          0.21               0.85              0.66

  **149**      1.24          0.51               0.70              0.11

  **153**      0.73          0.17               1.52              0.23

  **156**      NC            NC                 1.12              0.73

  **180**      0.94          0.78               0.98              0.96

  **183**      NC            NC                 0.99              0.96

  **187**      NC            NC                 0.87              0.70

  **194**      NC            NC                 1.45              0.23

  **196**      NC            NC                 2.11              0.04

  **201**      NC            NC                 1.59              0.20

  **206**      NC            NC                 2.04              0.05
  ----------------------------------------------------------------------------------

> \* Nanogram per gram lipid
>
> † Family members include parents/guardians only.
>
> ‡ Polychlorinated biphenyls
>
> § The estimated relative risk of leukemia associated with one standard
> error of the geometric mean increase in the blood or urine level of
> each chemical. Odds ratios are not reported if fewer than 60% of cases
> and controls had detectable levels of the chemical in their blood or
> urine.
>
> ^║^ The *P*-value estimates the probability that the deviation of the
> odds ratio from 1.0 (no difference in risk) is due to chance. A
> *P*-value less than 0.05 suggests that chance is unlikely to explain
> the deviation.
>
> \*\* Not calculated
>
> **The PCBs that were analyzed in the Churchill County investigation
> but that were detected in fewer than 60% of the participants are as
> follows:**

87 157 178

105 167 189

128 170 195

146 172 209

151 177

[]{#Table_9 .anchor}Table 9.\
Volatile Organic Compounds (μg/L)^\*^ in the Blood of the People Living
in the United States and People Living in Churchill County, Nevada

+----------------+--------------+--------+----------------+----------+
| **VOCs**)^†^   | **United     |        | **Churchill    |          |
|                | States**     |        | County**       |          |
+----------------+--------------+--------+----------------+----------+
|                | **Arithmetic | **     | **Arithmetic   | **% \>   |
|                | Mean from    | 95^th^ | Mean of Total  | U.S.     |
|                | NHANES       | Percen | Study          | 95^th^   |
|                | III^‡^**     | tile** | Population**   | perc     |
|                |              |        |                | entile** |
+----------------+--------------+--------+----------------+----------+
| **1,1,1-Tri    | 0.34         | 0.8    | NC             | 0.0      |
| chloroethane** |              |        |                |          |
+----------------+--------------+--------+----------------+----------+
| **1,4-Dic      | 1.9          | 9.2    | 0.2            | 0.0      |
| hlorobenzene** |              |        |                |          |
+----------------+--------------+--------+----------------+----------+
| **2,5-D        | Smokers =    | NA*    | NC             | Could    |
| imethylfuran** | 0.14         | *^§^** |                | not      |
|                |              |        |                | c        |
|                | Nonsmokers = |        |                | alculate |
|                | 0.024        |        |                |          |
+----------------+--------------+--------+----------------+----------+
| **Benzene**    | 0.13         | 0.48   | NC             | --       |
+----------------+--------------+--------+----------------+----------+
| **Carbon       | NC^║^        | NC     | NC             | --       |
| t              |              |        |                |          |
| etrachloride** |              |        |                |          |
+----------------+--------------+--------+----------------+----------+
| **             | 0.11         | 0.25   | 0.07           | 2.0      |
| Ethylbenzene** |              |        |                |          |
+----------------+--------------+--------+----------------+----------+
| *              | 0.37         | 0.78   | 0.31           | 1.5      |
| *m-/p-Xylene** |              |        |                |          |
+----------------+--------------+--------+----------------+----------+
| **o-Xylene**   | 0.14         | 0.28   | 0.08           | 1.5      |
+----------------+--------------+--------+----------------+----------+
| **Styrene**    | 0.074        | 0.18   | 0.009          | 7.3      |
+----------------+--------------+--------+----------------+----------+
| **Tetrach      | 0.19         | 0.62   | 0.3            | 3.4      |
| loroethylene** |              |        |                |          |
+----------------+--------------+--------+----------------+----------+
| **Toluene**    | 0.52         | 1.5    | 0.32           | 0.5      |
+----------------+--------------+--------+----------------+----------+
| **Trich        | 0.017        | 0.021  | NC             | 4.4      |
| loroethylene** |              |        |                |          |
+----------------+--------------+--------+----------------+----------+

> \* Micrograms per liter
>
> † Volatile Organic Compounds.
>
> ‡ VOC data were not reported in the *Second National Report on Human
> Exposure to Environmental Chemicals*, 2003.
>
> § Not available. The 95^th^ percentile for this VOC was not reported
> in the study we used as a reference.
>
> ║ Not Calculated was used when less than 60% of the study population
> had detectable levels of this chemical.

[]{#Table_10 .anchor}Table 10.\
The Estimated Risk of Childhood Leukemia Associated with Blood Levels of
Volatile Organic Compounds (μg/L)^\*^ for Case Children and Families
Compared with Control Children and Families Living in Churchill County

  ----------------------------------------------------------------------------------------------
                            **Case vs.                      **Case vs.        
                            Comparison                      Comparison        
                            (Child)**                       (Families)^†^**   
  ------------------------- ------------ ------------------ ----------------- ------------------
  **VOC ^‡^**               **Odds       ***P*-Value**^║^   **Odds Ratio^§^** ***P*-Value**^║^
                            Ratio^§^**                                        

  **1,4-Dichlorobenzene**   NC^¶^        NC                 1.33              0.28

  **Ethylbenzene**          2.67         0.04               1.14              0.56

  **m-/p-Xylene**           0.80         0.74               0.87              0.60

  **O-Xylene**              1.45         0.47               1.01              0.98

  **Styrene**               1.21         0.62               1.25              0.30

  **Tetrachloroethylene**   0.32         0.19               0.38              0.01

  **Toluene**               0.77         0.70               1.12              0.67
  ----------------------------------------------------------------------------------------------

\* Nanogram per gram lipid

> † Family members include children and their parents/guardians.
>
> ‡ Volatile organic compounds
>
> § The estimated relative risk of leukemia associated with one standard
> error of the geometric mean increase in the blood or urine level of
> each chemical. Odds ratios are not reported if fewer than 60% of cases
> and controls had detectable levels of the chemical in their blood or
> urine.
>
> ^║^ The *P*-value estimates the probability that the deviation of the
> odds ratio from 1.0 (no difference in risk) is due to chance. A
> *P*-value less than 0.05 suggests that chance is unlikely to explain
> the deviation.
>
> ¶ Not calculated. Less than 60% of the study population had detectable
> levels of this chemical.
>
> **The VOCs that were analyzed in the Churchill County investigation
> but that were detected in fewer than 60% of the participants were:**

Trichloroethylene

Benzene

Carbon tetrachloride

1,1,1-Trichloroethane

2,5-Dimethylfuran

Table 11.\
Selected Exposure Information Collected Through Questionnaire and
Interview from the Churchill County Study Population

  ------------------------------------------------------------------------------------------
  **Exposure**                  **Total study  **Case       **Comparison   **p-value^\*^**
                                population**   children**   children**     
  ----------------------------- -------------- ------------ -------------- -----------------
  Maternal age at child's birth 26.31 yrs      27.93 yrs    25.89 yrs      0.20
  (n=67)                                                                   

  Paternal age at child's birth 29.19 yrs      32.36 yrs    28.36 yrs      0.03
  (n=67)                                                                   

  Mean birth weight of study    120.08 oz      121.83 oz    119.67 oz      0.59
  child (n=64)                                                             

  Mothers born outside U.S.     10.94 %        21.43 %      8.00 %         0.17
  (n=64)                                                                   

  Fathers born outside U.S.     14.52 %        28.57 %      10.42 %        0.19
  (n=62)                                                                   

  Hispanic ethnicity (n=66)     15.2 %         28.57 %      11.54 %        0.20

  Adult military service        27.94 %        42.86 %      24.07 %        0.19
  between year before birth and                                            
  date of diagnosis (n=68)                                                 

  Currently own cat (n=68)      33.82 %        14.29 %      38.89 %        0.12

  International birth of study  5.88 %         7.14 %       5.56 %         1.00
  child (n=68)                                                             
  ------------------------------------------------------------------------------------------

\* *P*-value from Fisher's exact test for proportions and t-test for
means.

Table 12\
Measure of Association with Infection Status Among Case and Comparison
Subjects^\*^

  ---------------------------------------------------------------------------------------------------------------
                 **Number of               **Number of                                              
                 Case                      Comparison                                               
                 Subjects**                Subjects**                                               
  -------------- ------------ ------------ ------------ ------------ ---------------- ------------- -------------
  **Population   **Positive   **Negative   **Positive   **Negative   **Odds           **95% CI**    **P-value**
  of Interest**  for EBV**    for EBV**    for EBV**    for EBV**    Ratio(Positive                 
                                                                     vs. Negative)**                

  **Children**   5            8            27           20           0.41             (0.07-1.92)   0.32
  ---------------------------------------------------------------------------------------------------------------

\* The results of all other viral testing were negative. Therefore
statistical analysis could only be using EBV serology results.

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