Affinity for risky behaviors following prenatal and early childhood exposure to tetrachloroethylene (PCE)-contaminated drinking water: a retrospective cohort study.

Abstract

Many studies of adults with acute and chronic solvent exposure have shown adverse effects on cognition, behavior and mood. No prior study has investigated the long-term impact of prenatal and early childhood exposure to the solvent tetrachloroethylene (PCE) on the affinity for risky behaviors, defined as smoking, drinking or drug use as a teen or adult.
This retrospective cohort study examined whether early life exposure to PCE-contaminated drinking water influenced the occurrence of cigarette smoking, alcohol consumption, and drug use among adults from Cape Cod, Massachusetts.
Eight hundred and thirty-one subjects with prenatal and early childhood PCE exposure and 547 unexposed subjects were studied. Participants completed questionnaires to gather information on risky behaviors as a teenager and young adult, demographic characteristics, other sources of solvent exposure, and residences from birth through 1990. PCE exposure was estimated using the U.S. EPA's water distribution system modeling software (EPANET) that was modified to incorporate a leaching and transport model to estimate PCE exposures from pipe linings.
Individuals who were highly exposed to PCE-contaminated drinking water during gestation and early childhood experienced 50-60% increases in the risk of using two or more major illicit drugs as a teenager or as an adult (Relative Risk (RR) for teen use = 1.6, 95% CI: 1.2-2.2; and RR for adult use = 1.5, 95% CI: 1.2-1.9). Specific drugs for which increased risks were observed included crack/cocaine, psychedelics/hallucinogens, club/designer drugs, Ritalin without a prescription, and heroin (RRs:1.4-2.1). Thirty to 60% increases in the risk of certain smoking and drinking behaviors were also seen among highly exposed subjects.
The results of this study suggest that risky behaviors, particularly drug use, are more frequent among adults with high PCE exposure levels during gestation and early childhood. These findings should be confirmed in follow-up investigations of other exposed populations.

Full text

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RESEARCHOpen Access
Affinity for risky behaviors following prenatal and
early childhood exposure to tetrachloroethylene
(PCE)-contaminated drinking water:
a retrospective cohort study
Ann Aschengrau1*, Janice M Weinberg2, Patricia A Janulewicz1, Megan E Romano1,3, Lisa G Gallagher4,
Michael R Winter5, Brett R Martin5, Veronica M Vieira4, Thomas F Webster4, Roberta F White4,6and
David M Ozonoff4
Abstract
Background: Many studies of adults with acute and chronic solvent exposure have shown adverse effects on
cognition, behavior and mood. No prior study has investigated the long-term impact of prenatal and early
childhood exposure to the solvent tetrachloroethylene (PCE) on the affinity for risky behaviors, defined as smoking,
drinking or drug use as a teen or adult.
Objectives: This retrospective cohort study examined whether early life exposure to PCE-contaminated drinking
water influenced the occurrence of cigarette smoking, alcohol consumption, and drug use among adults from
Cape Cod, Massachusetts.
Methods: Eight hundred and thirty-one subjects with prenatal and early childhood PCE exposure and 547
unexposed subjects were studied. Participants completed questionnaires to gather information on risky behaviors
as a teenager and young adult, demographic characteristics, other sources of solvent exposure, and residences
from birth through 1990. PCE exposure was estimated using the U.S. EPA’s water distribution system modeling
software (EPANET) that was modified to incorporate a leaching and transport model to estimate PCE exposures
from pipe linings.
Results: Individuals who were highly exposed to PCE-contaminated drinking water during gestation and early
childhood experienced 50-60% increases in the risk of using two or more major illicit drugs as a teenager or as an
adult (Relative Risk (RR) for teen use = 1.6, 95% CI: 1.2-2.2; and RR for adult use = 1.5, 95% CI: 1.2-1.9). Specific
drugs for which increased risks were observed included crack/cocaine, psychedelics/hallucinogens, club/designer
drugs, Ritalin without a prescription, and heroin (RRs:1.4-2.1). Thirty to 60% increases in the risk of certain smoking
and drinking behaviors were also seen among highly exposed subjects.
Conclusions: The results of this study suggest that risky behaviors, particularly drug use, are more frequent among
adults with high PCE exposure levels during gestation and early childhood. These findings should be confirmed in
follow-up investigations of other exposed populations.
* Correspondence: aaschen@bu.edu
1Department of Epidemiology, Boston University School of Public Health,
Talbot 3E, 715 Albany Street, Boston, MA 02118, USA
Full list of author information is available at the end of the article
Aschengrau et al. Environmental Health 2011, 10:102
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© 2011 Aschengrau et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative
Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and
reproduction in any medium, provided the original work is properly cited.

Page 2

Background
In 1980 government officials in New England learned
that tetrachloroethylene (PCE) was leaching into public
drinking water supplies from the vinyl lining (VL) of
asbestos cement (AC) water distribution pipes. The
liner, which was used since the late 1960s to address
alkalinity problems, had been sprayed onto the inner
pipe surface in a slurry of vinyl toluene resin and PCE.
Because the pipes were allowed to dry for 48 hours
before shipping [1] it was assumed that most of the PCE
had evaporated by the time the pipes were installed.
However, more than a decade passed before officials dis-
covered that sizeable quantities of PCE had remained in
the lining and were leaching into the drinking water
supplies.
Surveys done after the discovery of contamination
estimated that approximately 660 miles of VL/AC pipes
had been installed in nearly 100 cities and towns in
Massachusetts [2]. Because VL/AC pipes were installed
in response to replacement and expansion needs in a
town’s water system, the contamination pattern was
irregular and neighboring residents often had vastly dif-
ferent exposure levels. PCE levels in water samples
taken in 1980 ranged from 1.5 to 80 ug/L in medium
and high flow locations and 1,600 to 7,750 ug/L in low-
flow locations such as dead end streets [1]. Replacing
the VL/AC pipes was prohibitively expensive, and so
officials initiated a program of flushing and bleeding to
reduce levels below 40 μg/l, the action level in 1980
based on the U.S. EPA Suggested No Adverse Response
Level (SNARL) [1]. Currently, the maximum contami-
nant level for PCE is set at 5 μg/L. Exposure to PCE
from drinking water occurs by direct ingestion, dermal
exposure during bathing and, because it volatilizes
easily, by inhalation during showering, bathing and
other household uses.
PCE is a well-recognized animal and human neurotox-
icant [3]. Many epidemiologic studies of adults with
occupational exposure to PCE and other solvents report
impairments in cognition, memory, attention, and
executive function [4-9]. Mood changes, including
increases in anxiety and depression, have also been
reported [4,6,7,10,11].
The published literature examining neurotoxic effects
among children with prenatal and childhood exposure
to organic solvents including PCE, on the other hand, is
comparatively small and results are not consistent [12].
Four studies found no deficits in cognitive and beha-
vioral function or no increases in disorders of attention
and learning [13-16], while two found lower tests scores
and more behavioral problems among children with pre-
natal or early childhood exposure to organic solvents
[17,18]. No prior studies have examined possible long-
lasting neurological consequences of early life exposure.
Thus, we undertook a population-based retrospective
cohort study to examine the long-term neurotoxic
effects of prenatal and early childhood exposure to PCE
contaminated drinking water. The current report
focuses on the affinity for three risky behaviors: cigarette
smoking, alcoholic beverage consumption, and drug use
as a teenager and adult. The suspicion that prenatal and
early childhood exposure to PCE might increase the
occurrence of these behaviors stems from reports that
prenatal exposure to another organic solvent –alcohol–
increases the risk of these behaviors during adolescence
and early adulthood [19,20].
Methods
Selection of Study Population
Subjects were eligible for the study if they were born
during 1969-1983 to married women living in Cape
Cod, Massachusetts towns known to have some VL/AC
water pipes installed in some parts of their water distri-
bution system. Such a study subject is called an “index
subject.” Eight towns in the study area were affected
–Barnstable, Bourne, Falmouth, Mashpee, Sandwich,
Brewster, Chatham, and Provincetown–each having any-
where from one to 50 miles of VL/AC pipes [2]. Eligible
subjects were identified by reviewing more than 13,000
birth certificates and cross-matching the maternal
address on the certificate with information collected
from water companies on the location, installation year,
and diameter of all VL/AC pipes in the water distribu-
tion system.
Initially, two groups of index subjects were selected:
(1) those born to women who were exposed to PCE-
contaminated drinking water at birth, and (2) those
born to women who were unexposed at their birth.
Index subjects were initially designated as “exposed”
because their birth residence was either directly adjacent
to a VL/AC pipe or because the residence was adjacent
to a pipe connected to a VL/AC pipe and the only pos-
sible water flow to the residence was through the VL/
AC pipe. Thus, the initial exposure status was based on
a visual inspection of maps depicting the pipe distribu-
tion network in the immediate vicinity of the birth
address. The initial “exposed” group included 1,910 sub-
jects. A comparison group initially designated as “unex-
posed” was randomly selected from the remaining
resident births during this period. “Unexposed” subjects
were frequency matched to “exposed” subjects on
month and year of birth. The initial “unexposed” group
included 1,928 subjects.
In addition, 1,202 older siblings of the “index” subjects
were identified for the present study. Only siblings born
in Massachusetts during 1969-1983 were eligible for
selection. All older siblings were initially considered
“unexposed” at birth because they were born before the
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family moved to an affected Cape Cod residence. How-
ever, the initial exposure status of all subjects was con-
sidered tentative until more extensive exposure
assessments, as described below, were completed.
Birth certificates of all subjects were reviewed to
obtain information on the study family, including the
full names of the subject and parents; the subject’s date
of birth, birth weight and gestational duration; and the
parents’ ages and educational levels when the subject
was born. All mothers were married at the time of the
index subject’s birth. The study was approved by the
Institutional Review Boards (IRB) of the Massachusetts
Department of Public Health and Boston University
Medical Center and by the 24A/B/11B Review Commit-
tee at the Massachusetts Department of Public Health.
Follow-Up and Enrollment of Study Subjects
Follow-up and enrollment of subjects occurred during
2006-2008. Subjects were traced to obtain their current
address and telephone number using resources such as
Massachusetts Resident’s Lists; death, credit bureau, and
alumni records; telephone books, directory assistance,
and the Internet White Pages. Letters were sent to all
successfully traced subjects describing the general pur-
pose of the study and requesting that they complete a
self-administered questionnaire. Three follow-up letters
were sent to non-respondents, and subjects who did not
respond to these letters were phoned if their telephone
number was available. As described in Table 1, 6.6% of
the selected population could not be located (n = 332),
45.5% were located but never responded to any of our
contact attempts (n = 2,294), 3.7% refused to participate
(n = 187), and 2.2% were deceased (n = 111). In addi-
tion, the Massachusetts Department of Public Health
IRB did not allow us to contact another 8.5% of subjects
whose parent had refused to participate in our prior
cohort study of reproductive and developmental out-
comes (n = 427, Aschengrau et al, 2008). These percen-
tages were similar for both “exposed” and “unexposed”
index subjects and their older siblings.
We conducted analyses comparing available character-
istics among participants and non-participants. Most
obtainable characteristics were similar, including initial
PCE exposure status (36.7% of participants vs. 38.8% of
non-participants were exposed), race (98.5% of partici-
pants vs. 97.3% of non-participants were White), age
(mean age as of June 30, 2007 was 29.3 years for partici-
pants and 28.9 years for non-participants), birth order
(47.7% of participants vs. 45.1% of non-participants were
first born), mean duration of gestation (40.1 weeks for
participants vs. 39.9 weeks for non-participants) mean
birth weight (3,428 grams for participants vs. 3,401 for
Table 1 Selection, enrollment, and initial and final exposure status of study subjects
Initial Exposure Status
Index Subject
Unexposed
Older Sibling
UnexposedExposedTotal
Selected
Excluded during enrollment
Deceased
Parent refused participation
Never located
No response
Refused
Returned questionnaire
Percent of selected
Percent of located
Excluded during exposure assessment
Inadequate residential history
Off-Cape address in potential
VL/AC town
Available for analysis
Percent of selected
Final exposure status
Both prenatal and early
childhood exposure
Only early childhood
exposure
Unexposed
19101928 12025040
35
199
113
871
73
619
32.4%
39.6%
40
148
149
887
78
626
32.5%
39.3%
36
80
70
536
36
444
36.9%
43.7%
111
427
332
2294
187
1689
33.5%
40.5%
15
19
37
27
29
50
81
96
585
30.6%
562
29.1%
365
30.4%
1512
30.0%
561 160110831
74285134
17360170547
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non-participants), While participants were more likely to
be female (60.7% of participants vs. 43.5% of non-parti-
cipants), and have mothers with some college education
(61.0% for participants vs. 49.3% for non-participants),
these differences were present for both exposed and
unexposed non-participants.
A self-administered questionnaire was sent to all suc-
cessfully traced subjects to gather information on cigar-
ette smoking, alcoholic beverage consumption, and drug
use. In particular, information was obtained on: (1) ever
becoming a regular cigarette smoker, age at initiation of
smoking on a regular basis, and smoking frequency and
amount during the past 30 days; (2) ever consuming an
alcoholic drink (defined as a 12 ounce bottle, can or
glass of beer; 12 ounces of wine cooler, hard lemonade,
or hard cider, a 4 ounce glass of wine, or a shot or
liquor straight or in a mixed drink); age at initiation of
drinking, typical drinking frequency and amount as a
teenager (ages 13 to 18 years), and drinking frequency
and amount during the past 30 days; and (3) ever use of
marijuana, inhalants, heroin, cocaine or crack, psychede-
lics or hallucinogens, Ritalin without a prescription, and
club drugs as a teenager (ages 13 to 18 years) and adult
(ages 19+ years).
The questionnaire also gathered information on the
subject’s demographic characteristics including race, eth-
nicity, current marital status, educational level and occu-
pation; personal history of learning disabilities and
mental disorders; family history of learning disabilities
and mental disorders; and occupational and non-occu-
pational exposure to solvents. Information was also col-
lected on the family’s residences from the subject’s birth
through 1990, including the exact street address and
calendar years of residence for all Cape Cod addresses.
Lastly, the survey collected information on the subject’s
knowledge of the PCE exposure episode and self-assess-
ments of their PCE exposure.
Additional questionnaire data were also available for
81% of subjects whose mothers participated in our prior
cohort study on the impact of PCE exposure on repro-
duction and development. These data included maternal
characteristics, such as changes in marital status; cigar-
ette smoking, alcoholic beverage consumption, mari-
juana use, medical and obstetrical complications, and
prenatal care during the subject’s gestation; breast feed-
ing practices; and exposure to solvents. Information on
the mother’s water use patterns during the subject’s
gestation and childhood was available for only 58% of
subjects and the prevalence of key variables was rela-
tively low (e.g., only 20% of mothers stated that they
regularly drank bottled water during the subject’s gesta-
tion) and so these data were not incorporated into our
present analyses.
Geocoding of Residential Addresses
All residential addresses on Cape Cod reported by sub-
jects were geocoded to a latitude and longitude using
ArcGIS 8.1. Whenever possible each address was geo-
coded to a parcel of land using information from the
questionnaire, county deeds, assessors’ maps, town voter
registration lists, and Internet resources. Addresses that
could not be geocoded to a specific parcel were geo-
coded to the closest parcel address by street number. If
a street number was unavailable and the street was less
than a mile long, the address was geocoded to the mid-
dle of the street. If the street was a mile or longer, the
address was geocoded to the intersection of the address
with the cross-street given in the survey. Approximately
95% of reported addresses were successfully geocoded.
The remainder could not be geocoded because insuffi-
cient information was provided by the subject. Geocod-
ing was done without knowledge of the exposure or
outcome status.
PCE Exposure Assessment
At the start of the study, we assigned an initial tentative
exposure status to each subject, as described above,
after visually inspecting maps of the pipe distribution
network in the immediate vicinity of the birth residence.
To determine the final exposure designation, we used a
leaching and transport model to estimate the mass of
PCE delivered to each residence from the prenatal per-
iod through the age of five years. The model, which was
developed for our prior epidemiological studies by
Webler and Brown [21,22], estimates the quantity of
PCE entering the drinking water using the initial
amount of PCE in the liner, the age of the pipe, and the
leaching rate of PCE from the liner into the water. The
pipe’s initial stock of PCE was based on the pipe’s dia-
meter and length. Laboratory experiments by Demond
suggested that the leaching process followed a simple
exponential relationship with rate constant of 2.25 years
[1]. Thus, PCE drinking water levels shortly after a VL/
AC pipe was installed were much higher than levels a
few years later.
The transport algorithm requires an estimate of water
flow rate and direction, which are functions of the con-
figuration of the pipes and number of water users. The
present study incorporated the Webler and Brown algo-
rithm into the publically available source code of the
EPANET water distribution modeling software to char-
acterize water flow throughout a town’s entire public
distribution system. EPANET, which was developed by
the U.S. EPA to help water utilities design water moni-
toring programs [23] has been applied in several other
epidemiological studies assessing the health effects of
drinking water contaminants [24-27], and because its
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source code is public ("open source”) we were able to
add the leaching and transport component.
We used maps of subject residences and the distribu-
tion systems to create a schematic depicting the water
sources, pipe characteristics, and nodes, representing
points of water consumption along the pipe. Informa-
tion on the locations, installation dates and diameters of
all VL/AC pipes in the public water supply were
obtained from local water departments and the Massa-
chusetts Department of Environmental Protection
(DEP).
We used the schematic to assign each residence to the
closest node on the distribution system. We assumed
that all users drew the same amount of water because
the study area was mainly comprised of residences.
Based on information in available records, we also
assumed that water sources did not change over the
study period. The distribution systems that were in
place in the 1960s and 1970s remained generally
unchanged until population growth required some
expansion in the 1980s.
The model incorporated these data to simulate the
instantaneous flow of water through each town’s net-
work and to estimate the mass of PCE delivered to each
node and all subject residences associated with the node
for each year of the study period. We were able to cal-
culate only annual PCE exposures because only move-in
and pipe installation years were available. We estimated
PCE exposure during the prenatal period by multiplying
the annual mass of PCE that entered the subject’s resi-
dence during their birth year by 9/12. We estimated
cumulative exposure during early childhood by sum-
ming the estimated mass of PCE that entered their resi-
dences from the month and year following birth
through the month and year of the fifth birthday. Simple
percentages were used to account for partial years.
We estimated PCE exposure levels only for subjects
with complete geocoded residential histories from birth
through age five. As seen in Table 1, a total of 81 sub-
jects were excluded because they had inadequate resi-
dential histories. Another 96 subjects were excluded
because one or more of their residences was in an off-
Cape town with some VL/AC pipe and our PCE expo-
sure assessments were limited to Cape Cod. Subjects
who reported living in a Cape Cod town without any
VL/AC pipes (n = 7) were assumed to have no PCE
exposure at that address. This was considered a reason-
able assumption because available records from this geo-
graphic area and time period indicated little or no PCE
contamination of these water sources.
Statistical Analysis
We compared the occurrence of each risk-taking beha-
vior among subjects with prenatal and early childhood
exposure combined to unexposed subjects. First, we
examined the impact of any PCE and then divided the
exposure into tertiles to examine a dose-response rela-
tionship. Nearly all subjects with prenatal exposure also
had childhood exposure and so we were unable to
examine the impact of prenatal exposure only. In addi-
tion, we did not examine the impact of exposure only
during childhood because there were too few subjects in
this category (n = 134) to provide stable effect estimates.
For the cigarette smoking outcomes, we examined ever
becoming a regular smoker, initiating smoking on a reg-
ular basis at a young age (defined as 13 years or under),
and becoming a heavy smoker as an adult (defined as 20
+ cigarettes per day in the past 30 days) in comparison
to never becoming a regular smoker. For drinking alco-
holic beverages, we examined initiating drinking at a
young age (13 or younger vs. 14 and older), high fre-
quency drinking as a teen (more than eight days a
month vs. never drinking as a teen), and heavy drinking
as a teen (five or more drinks per day for males and
four or more drinks per day for females vs. never drink-
ing as a teen). In addition, we examined high frequency
drinking as an adult (more than eight days a month in
past 30 days) and heavy drinking as an adult (five or
more drinks per day for males and four or more drinks
per day for females in past 30 days), all in comparison
to not drinking in the past 30 days. For illicit drug use,
we examined separately ever use of marijuana, inhalants,
heroin, crack/cocaine, psychedelics/hallucinogens, Ritalin
without a prescription, and club drugs/designer drugs as
a teen and adult in comparison to never using any
drugs at any time. Inhalants included glue, paint, gaso-
line, and cleaning solutions; psychedelics/hallucinogens
included “LSD,” “acid,” “PCP,” and mescaline; and club/
designer drugs included “Ecstasy,” “XTC,” “Special K,”
“GHB,” and “Liquid X.” In addition, we examined the
following groupings of illicit drug use as a teenager and
adult: any drugs, any major drugs (which included all
drugs, except marijuana), two or more drugs, and two
or more major drugs in comparison to never using any
drugs at any time. Lastly, we assessed the association
between PCE exposure and multiple risky behaviors by
examining the combinations of initiating drinking at a
young age, high frequency of drinking, and major drug
use as a teenager and heavy smoking, heavy drinking,
and major drug use as an adult.
The risk ratio (RR) was used to estimate the strength
of the association between PCE exposure and the occur-
rence of each behavior. Ninety-five percent confidence
intervals were used to assess the precision of the risk
ratios. Crude analyses were conducted on the entire
study population and repeated on a subset of subjects
whose mothers reported that they did not smoke cigar-
ettes or marijuana, or drink alcoholic beverages while
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they were pregnant with the study subject. Next, gener-
alized estimating equation (GEE) analyses were per-
formed to account for non-independent outcomes
arising from several children from the same family
[28,29]. Thirty-nine percent of the children in the study
were siblings. The logit link was used while assuming
equal correlation between birth outcomes from the
same mother.
Lastly, adjusted GEE analyses were conducted to con-
trol for confounding variables. Covariates considered for
these analyses were demographic characteristics, factors
associated with risk-taking behavior (e.g., maternal alco-
holic beverage consumption when she was pregnant
with the subject), and non-drinking water sources of sol-
vent exposure. These variables included the subject’s
gender, race, age when the study questionnaire was
completed, age at onset of puberty, breast feeding status,
and history of learning disabilities and mental illness;
the mother’s age and educational level when the subject
was born; paternal age, educational level and occupation
when the subject was born; the mother’s prenatal care,
multivitamin use, alcoholic beverage consumption,
cigarette smoking, marijuana use, medical conditions,
and obstetrical complications when she was pregnant
with the subject; number of prior live-born siblings;
death of a sibling; and maternal history of solvent expo-
sure. In order to determine which variables to control in
the adjusted analyses, we first assessed how strongly
each variable was associated with PCE exposure. Catego-
rical variables were retained for further consideration if
there was more than a 5% difference in the frequency of
a characteristic between compared groups. Variables
that met these criteria were maternal educational level
and paternal occupation at the subject’s birth, number
of prior live-born siblings, and the subject’s breast feed-
ing status. For example, there was a 5.2% difference
between exposed and unexposed subjects in the propor-
tion of mothers with some college education. Each of
these variables was entered into the crude GEE models
one at a time. However, because none of these variables
changed the crude GEE risk ratio by at least 10%, no
multivariate analyses were conducted.
Results
A total of 1,512 subjects was available for the analysis.
According to the initial exposure designation, there
were 585 exposed and 562 unexposed index subjects
and 365 unexposed older siblings (Table 1). Following
the more refined EPANET exposure assessment, 397
unexposed index subjects and older siblings changed
their status to exposed. These subjects had birth
addresses that were further downstream from a VL/AC
pipe than was originally considered exposed in the
initial visual assessment. The modeled assessment of the
entire distribution system indicated that these down-
stream locations had PCE contamination. In addition,
17 exposed index subjects changed their status to unex-
posed. These were either subjects whose modeled
assessment indicated a different water flow direction
than was originally assumed or subjects whose question-
naire data indicated that they used private wells as their
water supply. The final analytic population was com-
prised of 831 subjects with both prenatal and early
childhood exposure and 547 subjects with no exposure
during either period. The latter unexposed group
included 377 (= 17 + 360) index subjects and 170 older
siblings.
As shown in Table S1 (see Additional file 1), the
characteristics of the exposed and unexposed subjects
were quite similar. Subjects were predominantly
female, white, college-educated, in their late 20s, mar-
ried or cohabitating, and employed when they com-
pleted the study questionnaires. Few subjects had
possible occupational exposure to solvents but many
had potential exposure from hobbies and other
sources. Comparable proportions of exposed and unex-
posed index subjects also reported a personal history
of learning disabilities, repeating a grade, and mental
disorders (mainly depression), and a family history of
mental disorders (also mainly depression). Parental
characteristics were also similar, including their age,
educational level and occupation when the subject was
born. In addition, comparable proportions of mothers
reported smoking cigarettes and marijuana, drinking
alcoholic beverages, having prenatal care, and a history
of medical or obstetrical complications when they were
pregnant with the study subjects. The occurrence of
parental divorce and the death of a sibling were also
comparable.
The study population experienced a wide distribution
of PCE exposure levels that encompassed several orders
of magnitude (Table S2, Additional file 2). Cumulative
prenatal exposure levels were lower than early childhood
levels because of their different durations (i.e., nine
months vs. five years). Mean (SD) exposures were 32.6
(88.6) and 109.0 (283.3), respectively, for prenatal and
early childhood exposure.
As described, the exposure measures were based on
the mass of PCE delivered to a subject’s residence
through the water distribution system over the course of
a year. This annual mass of PCE was diluted in approxi-
mately 90,000 gallons of water, the average annual usage
for a family of four [30]. When we converted our PCE
exposure measures to annual point concentrations, we
estimated that PCE concentrations in water entering the
study homes ranged from less than 1 ug/L to 5,197 ug/
L. These levels are consistent with public water testing
results during the study period [1].
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Our comparison of each subject’s self-assessed expo-
sure status to that derived from the modeled assessment
revealed that only 7% of subjects considered exposed by
the modeled assessment thought that their drinking
water was contaminated, whereas 29% of these exposed
subjects thought that their water was not contaminated
and 64% were unsure. Similarly, we found that 31% of
subjects considered unexposed by the modeled assess-
ment thought that their drinking water was not con-
taminated while 5% thought that their drinking water
was contaminated and 63% were unsure.
Associations between PCE exposure and each risk-tak-
ing behavior are described below and are summarized in
Table 2 within the text. Analyses of the association
between any PCE exposure and cigarette smoking did
not reveal any meaningful increases in the risk of
becoming a regular smoker, initiating smoking at a
younger age, or smoking heavily in the past 30 days
among subjects with any exposure during gestation and
early childhood (Table 2; Table S3, Additional file 3).
However, when exposure levels were examined, small
increases in the risk of becoming a regular smoker (RR:
1.2, 95% CI: 1.0-1.5), initiating smoking at a younger age
(RR: 1.4, 95% CI: 0.8-2.5) and heavy smoking (RR: 1.3,
95% CI: 0.9-2.0) were observed among subjects in the
highest exposure tertile.
PCE exposure had a similar relationship with drinking
alcoholic beverages. There were no meaningful increases
in the risk of initiating drinking at a young age, drinking
frequently and heavily as a teen, and drinking frequently
and heavily in the past 30 days among subjects with any
exposure during gestation and early childhood (Table 2;
Table S4, Additional file 4). However, small to moderate
increases in the risk of drinking frequently as a teen
(RR: 1.6, 95% CI: 1.1-2.3) and drinking heavily in the
past 30 days (RR: 1.3, 95% CI: 1.0-1.7) were observed
among subjects in the highest exposure tertile.
Stronger associations were observed between PCE
exposure and drug use. Subjects with exposure during
both gestation and early childhood had 1.5- to 1.6-fold
increases in the risk of using crack/cocaine, club/
designer drugs, Ritalin without a prescription as a teen-
ager (Table 2; Table S5, Additional file 5), and 1.3- to
1.4-fold increases in the risk of using club/designer
drugs, Ritalin without a prescription, and heroin as an
adult (Table 2; Table S6, Additional file 6). Furthermore,
subjects in the highest tertile of prenatal and postnatal
exposure had greater increases in risk. In particular,
there were 1.4- to 2.1-fold increases in the risk of using
crack/cocaine, psychedelics/hallucinogens, club/designer
drugs, Ritalin without a prescription, and heroin as a
teenager (Table 2; Table S5, Additional file 5), and 1.4-
to 1.9-fold increases in the risk of using crack/cocaine,
psychedelics/hallucingens, club/designer drugs, Ritalin
without a prescription, and heroin as an adult (Table 2;
Table S6, Additional file 6).
Because use of these drugs often co-occurred in the
same individual, we also observed increases in the risk
of multiple drug use among exposed subjects (Table 2;
Tables S5 and S6, Additional files 5 and 6). In particu-
lar, we found a 40% increase in the risk of using two or
more major drugs as a teenager (95% CI: 1.0-1.8) among
subjects with any prenatal and early postnatal exposure
that rose to 60% among subjects in the highest exposure
tertile (95% CI: 1.2-2.2). We also found a 30% increase
in the risk of using multiple major drugs as an adult
(95% CI: 1.0-1.6) among subjects with any prenatal and
early postnatal exposure that increased to 50% among
subjects in the highest exposure tertile (95% CI: 1.2-1.9).
As expected, there was a high degree of overlap
between the teenager and adult drug users. For example,
nearly 78% of the subjects who reported using major
drugs as teens went on to use these drugs as adults. In
contrast, 18% of subjects who reported that they did not
use major drugs as teens became major drug users as
adults. Contrary to expectations, the joint occurrence of
smoking, drinking and drug use in the same individual
was relatively uncommon. For example, only 7.4% of the
study population (n = 99) reported engaging in two or
three of the following activities as a teen: initiating
smoking before 14 years, drinking more than 8 days a
month, and using major drugs, and only 13.8% (n =
182) reported engaging in two or three of the following
activities as an adult: heavy smoking, heavy drinking,
and using major drugs. Only 1.5% of the study popula-
tion (n = 20) reported engaging in all three activities as
a teen and 1.6% (n = 21) reported engaging in all three
activities as an adult. Only three subjects reported a his-
tory of all three activities as both a teen and an adult.
However, when we assessed the relationship between
prenatal and childhood PCE exposure and the occur-
rence of multiple risky behaviors (Table S7, Additional
file 7), we found a 2.7-fold increase in the risk (95% CI:
0.9-8.0) of engaging in the following behaviors as a teen:
initiating smoking at < 14 years, drinking alcoholic bev-
erages > 8 days/month, and using major drugs. This
rose to a 5.4-fold increased risk among subjects in the
highest exposure tertile (95% CI: 1.7-17.0, Table S7,
Additional file 7). In addition, we found a 1.5-fold
increase in the risk (95% CI: 0.6-3.6) of engaging in the
following behaviors as an adult: smoking > 20 cigarettes
a day, drinking 5+/4+ alcoholic beverages per drinking
day, and using major drugs, rising to a 1.9-fold increased
risk among subjects in the highest exposure tertile (95%
CI: 0.6-5.7). Two-way combinations of these behaviors
were rare and not associated with PCE exposure.
The magnitude of the main associations observed for
smoking, drinking and drug use increased when the
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Table 2 Prenatal and Early Childhood Exposure to Tetrachloroethylene and Selected1Risky Behaviors
Outcome Exposure
Category/
Percentile
% Yes (n/N)Crude
RR (95% CI)
Simple GEE
RR (95% CI)
Ever smoked regularly vs. Never smoked regularly2
Any
> = 67th
33rd- < 67th
> 0- < 33rd
None
Any
> = 67th
33rd- < 67th
> 0-< 33rd
None
Any
> 67th
33rd- < 67th
> 0-< 33rd
None
Any
> 67th
33rd- < 67th
> 0-< 33rd
None
Any
> 67th
33rd- < 67th
> 0-< 33rd
None
Any
> 67th
33rd- < 67th
> 0-< 33rd
None
Any
> 67th
33rd- < 67th
> 0-< 33rd
None
Any
> 67th
33rd- < 67th
0-< 33rd
None
Any
> 67th
33rd- < 67th
> 0-< 33rd
None
Any
> 67th
33rd- < 67th
> 0-< 33rd
None
36.9 (303/821)
45.0 (122/271)
29.1 (81/278)
36.8 (100/272)
35.2 (191/543)
12.6 (75/593)
15.8 (28/177)
12.1 (27/224)
10.4 (20/192)
12.0 (48/400)
19.6 (159/811)
21.9 (59/269)
18.4 (51/277)
18.5 (49/265)
18.6 (98/528)
26.2 (68/260)
38.8 (33/85)
19.8 (18/91)
20.2 (17/84)
23.7 (42/177)
47.2 (133/282)
57.6 (53/92)
41.4 (36/87)
42.7 (44/103)
43.5 (83/191)
35.7 (124/347)
43.3 (45/104)
30.8 (40/130)
34.5 (39/113)
26.5 (59/223)
29.2 (92/315)
38.5 (37/96)
22.4 (26/116)
28.2 (29/103)
18.4 (37/201)
41.8 (160/383)
47.3 (53/112)
36.6 (52/142)
42.6 (55/129)
34.1 (85/249)
27.8 (86/309)
39.8 (39/98)
16.7 (18/108)
28.2 (29/103)
19.2 (39/203)
23.6 (69/292)
33.7 (30/89)
16.7 (18/108)
22.1 (21/95)
15.5 (30/194)
1.0 (0.9-1.2)
1.3 (1.1-1.5)
0.8 (0.7-1.0)
1.0 (0.9-1.3)
Reference
1.1 (0.8-1.5)
1.3 (0.9-2.0)
1.0 (0.6-1.6)
0.9 (0.5-1.4)
Reference
1.1 (0.8-1.3)
1.2 (0.9-1.6)
1.0 (0.7-1.3)
1.0 (0.7-1.4)
Reference
1.1 (0.8-1.5)
1.6 (1.1-2.4)
0.8 (0.4-1.5)
0.9 (0.5-1.4)
Reference
1.1 (0.9-1.3)
1.3 (1.0-1.7)
1.0 ((0.7-1.3)
1.0 (0.7-1.3)
Reference
1.4 (1.0-1.8)
1.6 (1.2-2.2)
1.2 (0.8-1.6)
1.3 (0.9-1.8)
Reference
1.6 (1.1-2.2)
2.1 (1.4-3.1)
1.2 (0.8-1.9)
1.5 (1.0-2.3)
Reference
1.2 (1.0-.1.5)
1.4 (1.1-1.8)
1.1 (0.8-1.4)
1.2 (1.0-1.6)
Reference
1.4 (1.0-2.0)
2.1 (1.4-3.0)
0.9 (0.5-1.4)
1.5 (1.0-2.2)
Reference
1.5 (1.0-2.3)
2.2 (1.4-3.4)
1.1 (0.6-1.8)
1.4 (0.9-2.4)
Reference
1.0 (0.9-1.2)
1.2 (1.0-1.5)
0.8 (0.7-1.0)
1.0 (0.9-1.3)
Reference
1.1 (0.8-1.5)
1.3 (0.9-2.0)
1.0 (0.7-1.6)
0.9 (0.5-1.4)
Reference
1.1 (0.8-1.3)
1.2 (0.9-1.6)
1.0 (0.7-1.4)
1.0 (0.7-1.4)
Reference
1.1 (0.8-1.5)
1.6 (1.1-2.3)
0.8 (0.5-1.3)
0.8 (0.5-1.4)
Reference
1.1 (0.9-1.3)
1.3 (1.0-1.7)
0.9 (0.7-1.3)
1.0 (0.7-1.3)
Reference
1.4 (1.0-1.8)
1.6 (1.2-2.2)
1.2 (0.8-1.6)
1.3 (0.9-1.8)
Reference
1.6 (1.1-2.2)
2.1 (1.4-3.0)
1.2 (0.8-1.9)
1.5 (0.9-2.3)
Reference
1.2 (1.0-1.5)
1.4 (1.1-1.8)
1.1 (0.8-1.4)
1.3 (1.0-1.6)
Reference
1.5 (1.0-2.1)
2.1 (1.5-3.1)
0.9 (0.5-1.5)
1.5 (0.9-2.3)
Reference
1.5 (1.0-2.2)
2.1 (1.4-3.3)
1.1 (0.6-1.8)
1.3 (0.8-2.2)
Reference
Smoked 20+ cigarettes a day vs. Never smoked regularly3
First drank at < = 13 years vs. 14+ years4
Drank > 8 days/mo as teen vs. Never drank as a teen5
Drank > = 5/4 drinks/drinking day in past 30 days
vs. Did not drink in past 30 days6
2+ Major drugs as a teen vs. Never used any drugs7,8
Crack/cocaine as a teen vs. Never used any drugs7,9
Psychedelics/Hallucinogens as a teen vs. Never used any drugs7,9
Club/Designer Drugs as a teen vs. Never used any drugs7,9
Ritalin without a prescription as teen vs. Never used any drugs7,9
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analysis was limited to subjects whose mothers, accord-
ing to their self reports, did not smoke cigarettes or
marijuana or drink alcoholic beverages during the sub-
ject’s gestation (Table S8, Additional file 8). In particu-
lar, subjects in the highest exposure tertile had a 2.9-
fold increased risk of frequent drinking as a teenager
(95% CI: 1.3-6.1), and a 2.3-fold increased risk of using
two or more major drugs as a teenager (95% CI: 1.3-
4.1), stemming mainly from increases in the risk of
using inhalants, crack/cocaine, psychedelics/hallucino-
gens, club/designer drugs, Ritalin with a prescription.
These subjects also had a 2.1- fold increase in the risk
of using two or more major drugs as an adult (95% CI:
1.3-3.5), due primarily to increases in the risk of using
crack/cocaine, club/designer drugs, and Ritalin with a
prescription.
Discussion
The results presented here suggest that risky behaviors
involving smoking, alcohol consumption and drug use
are increased among individuals who were exposed to
PCE-contaminated drinking water during gestation and
early childhood. In particular, the most highly exposed
subjects reported increases in the risk of using multiple
Table 2 Prenatal and Early Childhood Exposure to Tetrachloroethylene and Selected1Risky Behaviors (Continued)
2+ Major drugs as an adult vs. Never used any drugs7,10
Any
> 67th
33rd- < 67th
> 0-< 33rd
None
Any
> 67th
33rd- < 67th
> 0-< 33rd
None
Any
> 67th
33rd- < 67th
0-< 33rd
None
Any
> 67th
33rd- < 67th
> 0-< 33rd
None
Any
> 67th
33rd- < 67th
> 0-< 33rd
None
Any
> 67th
33rd- < 67th
> 0-< 33rd
None
44.5 (179/402)
53.9 (69/128)
37.1 (53/143)
43.5 (57/131)
34.7 (87/251)
43.5 (172/395)
53.2 (67/126)
34.3 (47/137)
43.9 (58/132)
36.2 (93/257)
42.1 (162/385)
48.7 (56/115)
33.8 (46/136)
44.8 (60/134)
34.7 (87/251)
45.1 (183/406)
52.0 (64/123)
38.8 (57/147)
45.6 (62/136)
34.4 (86/250)
28.5 (89/312)
38.5 (37/96)
19.6 (22/112)
28.8 (30/104)
20.0 (41/205)
9.0 (22/245)
11.9 (8/67)
5.3 (5/95)
10.8 (9/83)
6.8 (12/176)
1.3 (1.0-1.6)
1.6 (1.2-2.0)
1.1 (0.8-1.4)
1.3 (1.0-1.6)
Reference
1.2 (1.0-1.5)
1.5 (1.2-1.9)
0.9 (0.7-1.3)
1.2 (0.9-1.6)
Reference
1.2 (1.0-1.5)
1.4 (1.1-1.8)
1.0 (0.7-1.3)
1.3 (1.0-1.7)
Reference
1.3 (1.1-1.6)
1.5 (1.2-1.9)
1.1 (0.9-1.5)
1.3 (1.0-1.7)
Reference
1.4 (1.0-2.0)
1.9 (1.3-2.8)
1.0 (0.6-1.6)
1.4 (1.0-2.2)
Reference
1.3 (0.7-2.6)
1.8 (0.7-4.1)
0.8 (0.3-2.1)
1.6 (0.7-3.6)
Reference
1.3 (1.0-1.6)
1.5 (1.2-1.9)
1.1 (0.8-1.4)
1.2 (1.0-1.6)
Reference
1.2 (1.0-1.5)
1.4 (1.1-1.8)
0.9 (0.7-1.2)
1.2 (0.9-1.6)
Reference
1.2 (1.0-1.5)
1.4 (1.1-1.8)
1.0 (0.7-1.3)
1.3 (1.0-1.7)
Reference
1.3 (1.1-1.6)
1.5 (1.2-1.9)
1.1 (0.9-1.5)
1.3 (1.0-1.7)
Reference
1.4 (1.0-2.0)
1.9 (1.3-2.8)
1.0 (0.6-1.5)
1.4 (0.9-2.1)
Reference
1.3 (0.7-2.6)
1.7 (0.7-4.1)
0.8 (0.3-2.1)
1.6 (0.7-3.6)
Reference
Crack/cocaine as an adult vs. Never used any drugs7,11
Psychedelics/Hallucinogens as an adult vs. Never used any drugs7,11
Club/Designer Drugs as an adult vs. Never used any drugs7,11
Ritalin without a prescription as an adult vs. Never used any drugs7,11
Heroin as an adult vs. Never used any drugs7,11
1 Table includes key findings with more than five subjects in the referent group
2 Comparison excludes subjects who smoked 100+ cigarettes but never became regular smokers
3 Comparison excludes subjects who smoked < 20 cigarettes a day
4 Comparison excludes subjects who never drank as a teen
5 Comparison excludes subjects who drank < = 8 days/month as a teen
6 Comparison excludes subjects who drank < 5/4 drinks/drinking day in past 30 days
7 Referent group is comprised of subjects who never used drugs as a teen or an adult
8 Comparison excludes subjects who used only marijuana or one major drug as a teen
9 Comparison excludes subjects who used any other type of drug as a teen
10 Comparison excludes subjects who used only marijuana or one major drug as an adult
11 Comparison excludes subjects who used any other type of drug as an adult
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major drugs both as a teenager and as an adult. Specific
drugs for which elevated risks were observed included
crack/cocaine, psychedelics/hallucinogens, club/designer
drugs, Ritalin without a prescription, and heroin. Increases
in the risk of certain smoking and drinking behaviors were
also seen among the highest exposure group. Limiting the
analyses to subjects without prenatal exposure to maternal
cigarette smoking, marijuana use and alcohol consumption
strengthened these associations.
Any causal interpretation of these findings should
consider the following study limitations. First, the results
are likely affected by exposure misclassification. Because
historical exposure measurements were unavailable, we
estimated PCE exposure during the study period using
EPANET water distribution modeling software that was
modified to incorporate a leaching and transport model
[21,23]. The model was applied to water distribution
system conditions in 1980 and was assumed to be repre-
sentative of the entire exposure period. Furthermore, the
exposure assessment predicted the annual mass of PCE
delivered to each subject’s residence during gestation
and early childhood and, because information on mater-
nal water use was available for only 58% of the study
population, we did not incorporate these data into our
analyses. Results from validation studies indicate reason-
able correlation between our exposure estimates and
PCE concentrations in historical water samples [31,32],
but non-differential exposure misclassification likely
biased the findings from dichotomous comparisons (e.g.,
any exposure vs. none) towards the null [33]. The
expected direction of bias for comparisons involving the
exposure tertiles is more difficult to predict, but associa-
tions seen among subjects in the highest tertile are likely
to be attenuated while those in the middle category
could have either an upward or downward bias.
Another limitation stems from the use of self-reports
as the source of information on the risky behaviors.
While the prevalence of these behaviors among study
subjects is similar or higher than reported in indepen-
dent surveys of Cape Cod and other Massachusetts resi-
dents [34,35], some faulty reporting was likely. However,
since most subjects did not know their exposure status
(see results section), inaccurate reporting was likely to
be non-differential and so would not have affected the
risk ratios from this cohort study [36].
Still another limitation stems from possible residual con-
founding by some contextual feature of highly exposed
communities. In fact, 52% of highly exposed residents
came from the town of Falmouth. However, there was no
association between town of birth/residence and the pre-
valence of risky behaviors. For example, risk ratios for
multiple major drug use as a teen and as an adult were 1.1
and 1.0, respectively, when Falmouth residents were com-
pared to residents of the other study towns.
Residual confounding is also possible from missing
data on several risk factors for substance use during
childhood and adolescence, including parental smoking,
alcohol and drug use, poor parental supervision, peer
influences, behavior problems, and adverse events
[37-41]. In order to account for the associations
observed in this study, these factors would need to be
highly correlated with PCE exposure, an unlikely sce-
nario given the irregular pattern of the PCE contamina-
tion across the neighborhoods of Cape Cod. In fact, our
prior studies of this cohort also found little or no con-
founding for the associations being investigated [42,43].
Furthermore, the magnitude of most associations
increased when the analysis was restricted to subjects
whose mothers reported that they did not smoke cigar-
ettes or marijuana, or drink alcoholic beverages during
the subject’s gestation, suggesting that residual con-
founding by other similar factors could have led to a
downward bias.
A further limitation stems from the study’s low
response rate. Although this problem reduced the statis-
tical power of the study, the following evidence suggests
that it did not result in selection bias. First, most avail-
able characteristics of participants and non-participants
were similar, including initial PCE exposure status. Sec-
ond, while participants were more likely to be female
(60.7% of participants vs. 43.5% of non-participants),
and have mothers with some college education (61.0%
for participants vs. 49.3% for non-participants), these
differences were equally present for exposed and unex-
posed non-participants. Third, losses stemming from the
death of potential participants were small and unrelated
to initial PCE exposure status (n = 111, Table 1). In
addition, our review of death records from the Massa-
chusetts Registry of Vital Records and Statistics and the
National Death Index suggested that only four deaths
were associated with substance use; two of these deaths
occurred among exposed subjects and two occurred
among unexposed subjects.
Intermediate factors that may have contributed to a
subject’s decision to engage in risky behaviors include
early puberty [44], learning disabilities [45], and mental
illness [46]. Analyses of our study population do not
indicate any association between high PCE exposure and
either early puberty or learning disabilities [16]. Analyses
of the occurrence of mental illness in relation to early
life exposure to PCE are currently underway.
PCE’s potential to cause neurotoxic effects has been
established through numerous animal and human stu-
dies [3]. Because of its small size and fat solubility, PCE
readily crosses the blood brain barrier and has a high
affinity for the lipophilic tissues of the central nervous
system. Most epidemiologic studies of adults with occu-
pational exposure to PCE and related solvents have
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reported impairments in cognition, memory, attention,
and executive function [4-9]. Increases in anxiety and
depression have also been reported in several of these
studies [4,5,7,10,11].
As noted in the Introduction, studies of the neuro-
toxic effects among individuals with early life exposure
to organic solvents have produced mixed results. Eske-
nazi et al. found no deficits in intellectual ability, motor
skills or memory among pre-school children whose
mothers had jobs involving solvent exposure during
pregnancy [13]. In addition, no meaningful differences
were seen in two studies of cognitive and behavioral
function among children attending a nursery school and
day care center who were exposed to PCE from nearby
dry cleaning facilities [14,15]. Our prior cohort study on
the reproductive and developmental effects of prenatal
and early postnatal PCE exposure also did not observe
any associations with disorders of attention, learning,
and behavior throughout childhood [16]. In contrast,
Till et al. found that pre-school children whose mothers
were exposed to organic solvents during pregnancy had
lower scores on language tests, reduced graphomotor
skills, and more behavioral problems than unexposed
children [17]. In addition, Laslo-Baker et al. found that
preschool children with prenatal exposure to organic
solvent mixtures scored lower on tests of general intelli-
gence, language and motor skills [18]. The inconsistent
findings among these studies may stem from differences
in the sensitivity of measures used to assess deficits in
brain function [16].
To the best of our knowledge, no prior study has investi-
gated other lasting consequences of early life exposure to
PCE and related solvents. However, because PCE and alco-
hol have similar neurotoxic effects [3], two long-term birth
cohort studies of prenatal alcohol exposure provide perti-
nent data for comparison. A prospective cohort study
from Seattle, Washington found a significant association
between prenatal alcohol exposure and drinking problems
among offspring at age 14 and 21 years, even after control-
ling for family history of alcohol problems, prenatal mater-
nal smoking, prenatal and postnatal parental drug use,
postnatal parental alcohol use, and parenting style [19,47].
Another prospective cohort study from Brisbane, Australia
also found that prenatal alcohol exposure was associated
with heavy alcohol consumption and alcohol disorders
among offspring during adolescence and early adulthood
[20,48]. In particular, investigators observed a 2.74-fold
increase in the risk of consuming three or more drinks per
drinking occasion at age 14 years among offspring whose
mothers consumed at least three drinks per drinking occa-
sion during pregnancy (95% CI:1.70-4.22) [48]. Addition-
ally, they observed a 3.29-fold increased risk of developing
alcohol disorders at ages 18-21 years among offspring
whose mothers consumed at least three drinks per
drinking occasion during early pregnancy (95% CI: 1.74-
6.24) [20]. These investigators also adjusted for numerous
confounding variables, including gender, maternal smok-
ing, education, age, anxiety, depression, and child behavior.
While results from these two studies may be still be con-
founded by genetic predisposition and unmeasured envir-
onmental influences for alcohol consumption, they are
supported by animal data suggesting that early life expo-
sure to alcohol increases subsequent affinity, either by
creating a preference for similar stimuli or by developing
an association between alcohol’s odor and taste and its
pharmacological effect [49].
The mode of action by which PCE and other organic
solvents may cause neurological effects, including an
affinity for risky behaviors, is currently unknown [3].
There is evidence to support neurotoxic mechanisms
involving the peroxidation of cell membrane lipids [50],
changes in the fatty acid profile of the brain [51], and
loss of myelin [52]. In addition, experiments suggest
that the neurotoxic mechanism may involve ligand-
gated ion channel activity via the following receptors:
GABAA, glycine, NMDA, glutamate kainite, and AMPA
[53-57]. In fact, it has been suggested that exposure to
agents such as ethanol during synaptogenesis can trigger
substantial apoptotic neurodegeneration because these
agents interfere with the action of neurotransmitters
and GABAAreceptors [58].
In summary, the results of this study suggest that risky
behaviors, particularly drug use, are increased among
adults exposed to high levels of PCE during gestation and
early childhood. Because this study has several limitations
and is the first to report this association, these findings
should be confirmed in follow-up investigations of simi-
larly exposed populations. Because PCE remains a com-
monly used commercial solvent that exposes workers
and consumers and causes frequent contamination of
drinking water from groundwater sources, it is important
to determine its long-term impact on behavior.
Conclusions
Numerous studies of adults with acute and chronic solvent
exposure have shown adverse impacts on cognition,
executive function, behavior and mood. However, no prior
study has investigated the long-term impact of prenatal
and early childhood exposure to the prevalent organic sol-
vent tetrachloroethylene (PCE) on the development of
risky behaviors. We undertook a retrospective cohort
study to examine whether early life exposure to PCE-con-
taminated drinking water influenced the adoption of cigar-
ette smoking, alcohol consumption, and drug use among
adults from Cape Cod, Massachusetts. The results suggest
that these risky behaviors, particularly drug use, are
increased among adults with PCE exposure levels during
gestation and early childhood. Specific illicit drugs for
Aschengrau et al. Environmental Health 2011, 10:102
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which increased risks were observed included crack/
cocaine, pychedelics/hallucinogens, club/designer drugs,
Ritalin without a prescription, and heroin. Limiting the
analyses to subjects without prenatal exposure to maternal
cigarette smoking, marijuana use and alcohol consumption
strengthened these associations. Because this study has
many limitations and is the first to report this association,
additional long-term studies of similarly exposed popula-
tions are needed.
Additional material
Additional file 1: Table S1 Distribution of Selected Characteristics of
Subjects and Parents by PCE Exposure Status.
Additional file 2: Table S2 Distribution of Cumulative PCE Exposure
(in grams) among Exposed Subjects.
Additional file 3: Table S3 Prenatal and Early Childhood Exposure
to Tetrachloroethylene and the Risk of Cigarette Smoking.
Additional file 4: Table S4 Prenatal and Early Childhood Exposure
to Tetrachloroethylene and the Risk of Alcohol Use.
Additional file 5: Table S5 Prenatal and Early Childhood Exposure
to Tetrachloroethylene and the Risk of Teenage Drug Use.
Additional file 6: Table S6 Prenatal and Early Childhood Exposure
to Tetrachloroethylene and the Risk of Adult Drug Use.
Additional file 7: Table S7 Prenatal and Early Childhood Exposure
to Tetrachloroethylene and Multiple Risky Behaviors.
Additional file 8: Table S8 Prenatal and Early Childhood Exposure
to Tetrachloroethylene and Selected Risky Behaviors Among
Subjects Without a History of Prenatal Exposure to Cigarette
Smoke, Marijuana or Alcohol.
Abbreviations
CI: Confidence Interval; DEP: Department of Environmental Protection; GEE:
Generalized estimating equation; IRB: Institutional Review Board; PCE:
Tetrachloroethylene; RDD: Relative delivered dose; RR: Risk Ratio; SNARL:
Suggested no adverse response action level; VL/AC: vinyl-lined asbestos-
cement.
Acknowledgements
The authors would like to acknowledge the study participants who took the
time to share their experiences and the assistance of the local water
companies and the Massachusetts Department of Environmental Protection.
This work was supported by the National Institute of Environmental Health
Sciences Superfund Research Program 5P42ES00738. MER was supported, in
part, by a training grant from the National Institute of Child Health and
Human Development, NIH.
Author details
1Department of Epidemiology, Boston University School of Public Health,
Talbot 3E, 715 Albany Street, Boston, MA 02118, USA.2Department of
Biostatistics, Boston University School of Public Health, Crosstown, 715
Albany Street, Boston, MA 02118, USA.3Department of Epidemiology,
University of Washington, Box 357236, Seattle WA, 98195, USA.4Department
of Environmental Health, Boston University School of Public Health, Talbot
4W, 715 Albany Street, Boston, MA 02118, USA.5Data Coordinating Center,
Boston University School of Public Health, Crosstown, 715 Albany Street,
Boston MA 02118, USA.6Department of Neurology, Boston University School
of Medicine, 72 East Concord Street, Boston Ma 02118 USA.
Authors’ contributions
AA conceived the study and its design, coordinated data collection and
analysis, and drafted the initial manuscript. JW, PAJ, TW, and VV provided
technical input to data collection, exposure assessment, data analysis, and
manuscript preparation. MER and LG conducted the data collection,
geocoding, and exposure assessments. MRW and BRM participated in the
data collection and conducted the data analyses. DO and RFW provided
technical input to the study design, data collection, and manuscript
preparation. All authors read and approved the final manuscript.
Competing interests
Dr. David Ozonoff is Co-editor-in-Chief of Environmental Health. He has
recused himself from all decisions involving the acceptance and publication
of this manuscript. At the request of the Commonwealth of Massachusetts,
in 1980 Dr. Ozonoff was a witness in bankruptcy court in a suit against the
Johns-Manville Corporation, manufacturers of the ACVL water mains. He has
also, on occasion, testified in personal injury and property damage cases
involving exposure to tetrachloroethylene and trichloroethylene. Three years
ago, Dr. Aschengrau served as a consultant in a personal injury case
involving chlorinated solvent contamination. None of the parties in any
litigation supported, reviewed or had knowledge of this paper. None of the
other authors of this study have any competing interests.
Received: 3 May 2011 Accepted: 2 December 2011
Published: 2 December 2011
References
1.Demond AH: A source of tetrachloroethylene in the drinking water of
New England: an evaluation of toxicity of tetrachloroethylene and the
prediction of its leaching rates from vinyl-lined asbestos-cement pipe
[MS Thesis]. Cambridge, MA: Massachusetts Institute of Technology; 1982.
2.Commonwealth of Massachusetts, Department of Environmental Quality
Engineering: Status report on tetrachloroethylene contamination of
public drinking water supplies caused by vinyl-lined asbestos cement
pipe. 1982, 1-26.
3.U.S. EPA: IRIS Toxicological Review of Tetrachloroethylene
(Perchloroethylene) (External Review Draft). U.S. Environmental Protection
Agency, Washington, DC, EPA/635/R-08/011A; 2008.
4.White RF, Proctor SP, Echeverria D, Schweikert J, Feldman RG:
Neurobehavioral effects of acute and chronic mixed-solvent exposure in
the screen printing industry. Am J Ind Med 1995, 28:221-231.
5. Tsai SY, Chen JD, Chao WY, Wang JD: Neurobehavioral effects of
occupational exposure to low-level organic solvents among Taiwanese
workers in paint factories. Environ Res 1997, 73:146-155.
6.Daniell WE, Claypoole KH, Checkoway H, Smith-Weller T, Dager SR,
Townes BD, Rosenstock L: Neuropsychological function in retired workers
with previous long-term occupational exposure to solvents. Occup
Environ Med 1999, 56:93-105.
7.Bowler RM, Lezak M, Booty A, Hartney C, Mergler D, Levin J, Zisman F:
Neuropsychological dysfunction, mood disturbance, and emotional
status of munitions workers. Appl Neuropsychol 2001, 8:74-90.
8. Bockelmann I, Darius S, McGauran N, Robra BP, Peter B, Pfister EA: The
psychological effects of exposure to mixed organic solvents on car
painters. Disabil Rehabil 2002, 24:455-461.
9. Wood RL, Liossi C: Long-term neuropsychological impact of brief
occupational exposure to organic solvents. Arch Clin Neuropsychol 2005,
20:655-665.
10.Morrow LA, Gibson C, Bagovich GR, Stein L, Condray R, Scott A: Increased
incidence of anxiety and depressive disorders in persons with organic
solvent exposure. Psychosom Med 2000, 62:746-750.
11. Condray R, Morrow LA, Steinahuer SR, Hodgson M, Kelley M: Mood and
behavioral symptoms in individuals with chronic solvent exposure.
Psychiatry Res 2000, 97:191-206.
12. Brown Dzubow R, Makris S, Siegel Scott C, Barone S: Early lifestage
exposure and potential developmental susceptibility to
tetrachloroethylene. Birth Defects Res B Dev Reprod Toxicol 2010, 89:50-65.
13. Eskenazi BL, Gaylord L, Bracken MB, Brown D: In utero exposure to organic
solvents and human neurodevelopment. Dev Med Child Neurol 1988,
30:492-501.
14. Spector J, Lewandowski AG, Mott JA, Schreiber JS: Neuropsychological and
behavioral functioning in tetrachloroethylene-exposed preschool
children and controls. Arch Clin Neuropsychol 1999, 14:661-662.
15.New York State Department of Health: Improving human risk assessment
for tetrachloroethylene by using biomarkers and neurobehavioral
Aschengrau et al. Environmental Health 2011, 10:102
http://www.ehjournal.net/content/10/1/102
Page 12 of 13

Page 13

testing. Final Technical Report for US EPA STAR Grant #R827446 2005 [http://
www.epa.gov/ncer/final/r827446fr.pdf], Accessed January 11, 2011.
Janulewicz PA, White RF, Winter MR, Weinberg JM, Gallagher LE, Vieira V,
Webster TF, Aschengrau A: Risk of learning and behavioral disorders
following prenatal and early postnatal exposure to tetrachloroethylene
(PCE)-contaminated drinking water. Neurotoxicol Teratol 2008, 30:175-185.
Till C, Koren G, Rovet JF: Prenatal exposure to organic solvents and child
neurobehavioral performance. Neurotoxicol Teratol 2001, 23:235-245.
Laslo-Baker D, Barrera M, Knittel-Keren D, Kozer E, Wolpin J, Khattak S,
Hackman R, Rovet J, Koren G: Child neurodevelopmental outcome and
maternal occupational exposure to solvents. Arch Pediatr Adolesc Med
2004, 158:956-961.
Baer JS, Sampson PD, Barr HM, Connor PD, Streissguth AP: A 21-year
longitudinal analysis of the effetcs of prenatal alcohol exposure on
young adult drinking. Arch Gen Psychiatry 2003, 60:377-385.
Alati R, Al Mamun A, Williams GM, O’Callaghan M, Najman JM, Bor W: In
utero alcohol exposure and prediction of alcohol disorders in early
adulthood. Arch Gen Psychiatry 2006, 63:1009-1016.
Webler T, Brown HS: Exposure to tetrachloroethylene via contaminated
drinking water pipes in Massachusetts: a predictive model. Arch Environ
Health 1993, 48:293-297.
Aschengrau A, Rogers S, Ozonoff D: Perchloroethylene-contaminated
drinking water and the risk of breast cancer: additional results from
Cape Cod, Massachusetts. Environ Health Perspect 2003, 111:167-173.
Rossman LA: EPANET users manual. Cincinnati, OH: U.S. Environmental
Protection Agency, Risk Reduction Engineering Laboratory 1994.
Aral MM, Maslia ML, Ulirsch GV, Reyes JJ: Estimating exposure to volatile
organic compounds from municipal water-supply systems: use of a
better computational model. Arch Environ Health 1996, 51:300-309.
Gallagher MD, Nuckols JR, Stallones L, Savitz DA: Exposure to
trihalomethanes and adverse pregnancy outcomes. Epidemiol 1998,
9:484-489.
Maslia ML, Sautner JB, Aral MM, Reyes JJ, Abraham JE, Williams RC: Using
water-distribution system modeling to assist epidemiologic
investigations. J Water Res Plan Mgmt 2000, 126:180-198.
Reif JS, Burch JB, Nuckols JR, Metzger L, Anger WK: Neurobehavioral effects
of exposure to trichloroethylene through a municipal water supply.
Environ Res 2003, 9:248-258.
Liang KY, Zeger SL: Longitudinal data analysis using generalized linear
models. Biometrika 1986, 73:13-22.
Zeger SL, Liang KY: Longitudinal data analysis for discrete and
continuous outcomes. Biometrics 1986, 42:121-130.
Massachusetts Water Resources Authority: Indoor Water Conservation.
[http://www.mwra.state.ma.us/comsupport/waterconservationmain.htm],
(accessed September 2011).
Spence L, Aschengrau A, Gallagher L, Webster T, Heeren T, Ozonoff D:
Evaluation of a model for estimating tetrachloroethylene exposure from
vinyl-lined asbestos-cement pipes. Environmental Health 2008, 7:24.
Gallagher LG, Vieira VM, Ozonoff D, Webster TF, Aschengrau A: Risk of
breast cancer following exposure to tetrachloroethylene-contaminated
drinking water in Cape Cod, Massachusetts: reanalysis using a modified
exposure assessment. Environ Health 2011, 19:47.
Aschengrau A, Seage GR: Essentials of Epidemiology in Public Health.
Sudbury MA: Jones and Bartlett Publishers;, 2 2008, 278-382.
Massachusetts Department of Health and Human Services: Massachusetts
Community Health Profile (MassCHIP) Health Data Base. 2007 [http://
www.mass.gov/dph/masschip], Accessed January 15, 2011.
Massachusetts Department of Public Health: Health of Massachusetts.
Boston, MA; 2010, 191-209.
Rothman KJ, Greenland S, Lash TL: Modern Epidemiology. Philadelphia:
Wolters Kluwer, Lippincott Williams and Wilkins;, 3 2008, 139-143.
Huurre T, Lintonen T, Kaprio J, Pelkonen M, Marttunen M, Aro H:
Adolescent risk factors for excessive alcohol use at age 32 years. A 16-
year prospective follow-up study. Soc Psychiatry Psychiatr Epidemiol 2010,
45:125-134.
Pilowsky DJ, Keyes KM, Hasin DS: Adverse childhood events and lifetime
alcohol dependence. Am J Public Health 2009, 99:258-263.
Hayatbakhsk MR, Mamun AA, Najman JM, O’Callaghan MJ, Bor W, Alati R:
Early childhood predictors of early substance use and substance use
disorders: prospective study. Aust N Z J Psychiatry 2008, 42:720-731.
16.
17.
18.
19.
20.
21.
22.
23.
24.
25.
26.
27.
28.
29.
30.
31.
32.
33.
34.
35.
36.
37.
38.
39.
40.Hayatbakhsk MR, Najman JM, Bor W, O’Callaghan MJ, Williams GM: Multiple
risk factor model predicting cannabis use and use disorders: a
longitudinal study. Am J Drug Alcohol Abuse 2009, 35:399-407.
Skeer M, McCormick MC, Normand SL, Buka SL, Gilman SE: A prospective
study of familial conflict, psychological stress, and the development of
substance use disorders in adolescence. Drug Alcohol Depend 2009,
104:65-72.
Aschengrau A, Weinberg J, Rogers S, Gallagher L, Winter M, Vieira V,
Webster T, Ozonoff D: Prenatal Exposure to Tetrachloroethylene-
contaminated Drinking Water and the Risk of Adverse Birth Outcomes.
Environ Health Perspect 2008, 116:814-820.
Aschengrau A, Weinberg J, Gallagher L, Winter M, Vieira V, Webster T,
Ozonoff D: Prenatal Exposure to Tetrachloroethylene-contaminated
Drinking Water and the Risk of Pregnancy Loss. Water Qual Expo Health
2009, 1:23-34.
Downing J, Bellis MA: Early pubertal onset and its relationship with
sexual risk taking, substance use and antisocial behavior: a preliminary
cross-sectional study. BMC Public Health 2009, 3:446.
McNamara J, Vervaeke SL, Willoughby T: Learning disabilities and risk-
taking behavior in adolescents: a comparison of those with and without
comorbid attention-deficit/hyperactivity disorder. J Learn Disabil 2008,
41:561-574.
Pedrelli P, Farabaugh AH, Zisook S, Tucker D, Rooney K, Katz J, Clain AJ,
Petersen TJ, Fava M: Gender, depressive symptoms and patterns of
alcohol use among college students. Psychopathology 2011, 44:27-33.
Baer JS, Barr HM, Bookstein FL, Sampson PD, Streissguth AP: Prenatal
alcohol exposure and family history of alcoholism in the etiology of
adolescent alcohol problems. J Stud Alcohol 1998, 59:533-543.
Alati R, Clavarino A, Najman JM, O’Callaghan M, Bor W, Al Mamun A,
Williams GM: The developmental origin of adolescent alcohol use:
findings from the Mater University study of pregnancy and its
outcomes. Drug and Alcohol Dependence 2008, 98:136-143.
Spear NE, Molina JC: Fetal or infantile exposure to ethanol promotes
ethanol ingestion in adolescence in adulthood: a theoretical review.
Alcohol Clin Exp Res 2005, 29:909-929.
Cojocel C, Beuter W, Muller W, Mayer D: Lipid peroxidation: a possible
mechanism of trichloroethylene-induced nephrotoxicity. Toxicol 1989,
55:131-141.
Kyrklund T, Haglid K: Brain lipid composition in guinea pigs after
intrauterine exposure to perchloroethylene. Pharmacol Toxicol 1991,
68:146-148.
Isaacson LG, Taylor DH: Maternal exposure to 1,1,2-trichloroethylene
affects myelin in the hippocampal formation of the developing rat. Brain
Res 1989, 488:403-407.
Mihic SJ: Acute effects of ethanol on GABAAand glycine receptor
function. Neurochem Int 1999, 35:115-123.
Yamakura T, Mihic SJ, Harris RA: Amino acid volume and hydropathy of a
transmembrane site determine glycine and anesthetic sensitivity of
glycine receptors. J Biol Chem 1999, 274:23006-23012.
Beckstead MJ, Weiner JL, Eger EI, Gong DH, Mihic SJ: Glycine and gamma-
aminobutyric acid (A) receptor function is enhanced by inhaled drugs of
abuse. Mol Pharmacol 2000, 57:1199-1205.
Cruz SL, Mirshahi T, Thomas B, Balster RL, Woodward JJ: Effects of the
abused solvent toluene on recombinant N-methyl-D-aspartate and non-
N-methyl-D-aspartate receptors expressed in Xenopus oocytes. J
Pharmacol Exp Ther 1998, 286:334-340.
Harris RA, Mihic SJ, Dildy-Mayfield JE, Machu TK: Actions of anesthetics on
ligand-gated ion channels: role of receptor subunit composition. FASEB
1995, 9:1454-1462.
Olney JW, Farber NB, Wozniak DF, Jevtovic-Todorovic V, Ikonomidou C:
Environmental agents that have the potential to trigger massive
apoptotic neurodegeneration in the developing brain. Environ Health
Perspect 2000, 108:383-388.
41.
42.
43.
44.
45.
46.
47.
48.
49.
50.
51.
52.
53.
54.
55.
56.
57.
58.
doi:10.1186/1476-069X-10-102
Cite this article as: Aschengrau et al.: Affinity for risky behaviors
following prenatal and early childhood exposure to tetrachloroethylene
(PCE)-contaminated drinking water: a retrospective cohort study.
Environmental Health 2011 10:102.
Aschengrau et al. Environmental Health 2011, 10:102
http://www.ehjournal.net/content/10/1/102
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