Exposure to Bisphenol A, Bisphenol F, and Bisphenol S in U.S. Adults and Children: The National Health and Nutrition Examination Survey 2013-2014

Abstract

Bisphenol F (BPF) and bisphenol S (BPS) are replacing bisphenol A (BPA) in the manufacturing of products containing polycarbonates and epoxy resins. Data on current human exposure levels of these substitutes are needed to aid in the assessment of their human health risks. This study analyzed urinary bisphenol levels in adults (N = 1808) and children (N = 868) participating in the National Health and Nutrition Examination Survey (NHANES) 2013–2014 and investigated demographic and lifestyle factors associated with urinary levels of bisphenols. BPA, BPS, and BPF were detected in 95.7, 89.4, and 66.5% of randomly selected urine samples analyzed as part of NHANES 2013–2014, respectively. Median levels of BPA in U.S. adult were higher (1.24 μg/L) than BPF and BPS levels (0.35 and 0.37 μg/L, respectively). For children, median BPA levels were also higher (1.25 μg/L) than BPF and BPS levels (0.32 and 0.29 μg/L, respectively). The limits of detection for BPA, BPF, and BPS were 0.2, 0.2, and 0.1 μg/L, respectively. Urinary levels showed associations with gender, race/ethnicity, family income, physical activity, smoking, and/or alcohol intake that depended on the specific bisphenol. The results of this study indicate that exposure of the general U.S. population to BPA substitutes is almost ubiquitous. Because exposures differ across the U.S. population, further studies of environmental, consumer, and lifestyle factors affecting BPF and BPS exposures are warranted.

Full text

Exposure to Bisphenol A, Bisphenol F, and Bisphenol S in U.S. Adults
and Children: The National Health and Nutrition Examination Survey
2013−2014
Hans-Joachim Lehmler,
†
Buyun Liu,
‡
Manuel Gadogbe,
†
and Wei Bao*
,‡
†
College of Public Health, Department of Occupational & Environmental Health, and
‡
College of Public Health, Department of
Epidemiology, University of Iowa, 145 N. Riverside Drive, Iowa City, Iowa 52242, United States
*
SSupporting Information
ABSTRACT: Bisphenol F (BPF) and bisphenol S (BPS) are
replacing bisphenol A (BPA) in the manufacturing of products
containing polycarbonates and epoxy resins. Data on current
human exposure levels of these substitutes are needed to aid in
the assessment of their human health risks. This study
analyzed urinary bisphenol levels in adults (N= 1808) and
children (N= 868) participating in the National Health and
Nutrition Examination Survey (NHANES) 2013−2014 and
investigated demographic and lifestyle factors associated with
urinary levels of bisphenols. BPA, BPS, and BPF were detected
in 95.7, 89.4, and 66.5% of randomly selected urine samples
analyzed as part of NHANES 2013−2014, respectively. Median levels of BPA in U.S. adult were higher (1.24 μg/L) than BPF
and BPS levels (0.35 and 0.37 μg/L, respectively). For children, median BPA levels were also higher (1.25 μg/L) than BPF and
BPS levels (0.32 and 0.29 μg/L, respectively). The limits of detection for BPA, BPF, and BPS were 0.2, 0.2, and 0.1 μg/L,
respectively. Urinary levels showed associations with gender, race/ethnicity, family income, physical activity, smoking, and/or
alcohol intake that depended on the specific bisphenol. The results of this study indicate that exposure of the general U.S.
population to BPA substitutes is almost ubiquitous. Because exposures differ across the U.S. population, further studies of
environmental, consumer, and lifestyle factors affecting BPF and BPS exposures are warranted.
■INTRODUCTION
Bisphenol A (BPA) (4,4′-(propane-2,2-diyl)diphenol) is a high-
volume industrial chemical, with a global consumption of
approximately 7.7 million metric tons in 2015, and the global
BPA demand is projected to increase to 10.6 million metric
tons by 2022.
1
BPA is used for the manufacturing of
polycarbonates and epoxy resins as well as various low-volume
specialty applications.
2,3
Because of growing human health
concerns, the use of BPA-based plastics in food and beverage
applications is under scrutiny. The use of BPA in baby bottles is
now prohibited in Canada, the European Union, and the
United States.
4−6
The European Chemical Agency (ECHA)
added BPA in 2017 to the Candidate List of substances of very
high concern. Because of the concern about its potential
toxicity in humans, BPA is increasingly replaced by structurally
similar chemicals, in particular bisphenol F (BPF) (4,4′-
dihydroxydiphenyl-methane) and bisphenol S (BPS) (4,4′-
sulfonylbisphenol), in the manufacturing of polycarbonates and
epoxy resins. BPF and BPS are also used in a variety of
common consumer products, for example, thermal paper.
7
According to ECHA, 1000 to 10 000 million metric tons of BPS
are manufactured or imported annually into the European
Economic Area. No production data for BPF are currently
registered with ECHA, suggesting that BPF is still a low use
chemical, at least in Europe.
8
BPA, BPF, and BPS have been detected in many environ-
mental samples, including soil, sediments, water, sewage
effluents, and sewage sludge.
9
They have a comparatively low
octanol−water coefficient (log Kow < 5), are readily
biotransformed in the environment, and do not bioaccumulate
and biomagnify in aquatic and terrestrial food chains.
3,9,10
BPA
typically is the most prevalent bisphenol analogue in the
environment; however, BPF and BPS are also frequently
detected in environmental samples from around the world.
Bisphenol analogues are present in a broad range of consumer
products and in foodstuffs, with BPA and BPF being major
contaminants present in foods from the United States.
11
BPF is
also a natural product present in mustard.
12
Environmental
exposure of humans to BPA and its substitutes (e.g., BPF)
occurs via the diet.
9,13,14
Dermal exposure to personal care and
other consumer products, ingestion of household dust, and
inhalation represent additional routes of exposure to bi-
sphenols.
15−18
Dermal contact with products containing
bisphenols, such as handling thermal receipt paper, represents
a source of occupational exposure to BPA and its substitutes.
19
Received: April 26, 2018
Accepted: May 30, 2018
Published: June 18, 2018
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BPA, BPF, and BPS are rapidly metabolized to the
corresponding glucuronides by mammalian uridine 5′-diphos-
phate-glucuronosyltransferases (UGTs).
20,21
As has been
shown for BPA, these glucuronides are rapidly eliminated
with urine in rats and humans.
22−24
Total urinary levels,
typically determined after deconjugation with β-glucuronidase/
sulfatase, are considered to be a robust biomarker for exposure
to bisphenols.
25
BPA is ubiquitous in humans and, for example,
was detected in earlier studies in >92% urine samples from the
U.S. population.
26−28
The limits of detection (LODs) for BPA,
BPS, and BPF were ≤0.4 μg/L in these studies.
26−28
BPA and
its metabolites have also been detected in human serum,
placental tissue, cord blood, and breast milk.
29
A human
biomonitoring study reported lower detection frequencies for
BPS (42 to 91%) in urine from several Asian countries
compared to those of BPA.
30
Japan and the U.S. were
exceptions, with detection frequencies of BPS in urine of 100
and 97%, respectively.
Several other studies also suggest that urinary levels of BPS
and BPF are currently lower compared to that of BPA.
28,30−32
For example, median concentrations of BPS in urine samples
from the Asian countries including China, India, Japan, Korea,
Kuwait, Malaysia, and Vietnam were 1 order of magnitude
lower than the median concentrations reported for BPA in the
same set of samples, with the exception of samples from
Japan.
30
Geometric means of urinary levels of BPF and BPS
were at least 3 and 30 times lower than those reported for BPA
in adults (age 26−84 years, N= 94) from South China.
31
Detection frequencies of 79.2% for BPA, 67.8% for BPS, and
40.2% for BPF were observed in urine samples from pregnant
women from the Netherlands (N= 1396) collected in 2004−
2005 (LODs < 0.18 μg/L).
32
Median levels of BPS and BPF
were lower compared to that of BPA in this study population.
Studies quantifying BPF and BPS in other human compart-
ments are limited, and both bisphenol analogues have relatively
small detection frequencies in human serum and breast
milk.
19,33,34
Taken together, the presence of BPA substitutes
in humans raises questions about their adverse human health
effects.
Table 1. Urinary Concentrations of BPA, BPF, and BPS in U.S. Adults in NHANES 2013−2014
a
BPA, μg/L BPF, μg/L BPS, μg/L
variable Nmedian (P25−P75) Pmedian (P25−P75) Pmedian (P25−P75) P
all 1808 1.24 (0.57−2.49) 0.35 (0.14−1.11) 0.37 (0.14−0.88)
age 20−39 years 598 1.47 (0.70−2.93) <0.001 0.36 (0.14−1.29) 0.86 0.43 (0.17−0.96) 0.64
40−59 years 607 1.18 (0.52−2.29) 0.34 (0.14−0.95) 0.35 (0.12−0.77)
≥60 years 603 1.04 (0.49−2.26) 0.34 (0.14−1.11) 0.32 (0.13−0.88)
gender male 851 1.39 (0.68−2.79) 0.002 0.41 (0.14−1.30) 0.03 0.41 (0.16−0.92) 0.08
female 957 1.09 (0.49−2.26) 0.29 (0.14−0.93) 0.33 (0.12−0.85)
race/ethnicity
b
non-Hispanic white 757 1.22 (0.53−2.38) 0.007 0.39 (0.14−1.21) 0.40 0.33 (0.12−0.74) 0.001
Hispanic 702 1.27 (0.66−2.55) 0.23 (0.14−0.64) 0.47 (0.21−0.96)
non-Hispanic black 383 1.82 (0.87−3.59) 0.41 (0.14−1.42) 0.62 (0.25−1.58)
other 266 0.89 (0.39−1.72) 0.24 (0.14−0.78) 0.29 (0.13−0.73)
education
c
less than high
school 429 1.30 (0.68−2.59) 0.93 0.28 (0.14−1.10) 0.20 0.48 (0.17−1.05) 0.32
high school 406 1.30 (0.59−2.63) 0.39 (0.14−1.27) 0.38 (0.17−0.91)
college or higher 973 1.21 (0.54−2.39) 0.35 (0.14−1.06) 0.34 (0.12−0.78)
family IPR
d
≤1.30 574 1.47 (0.68−2.91) 0.08 0.31 (0.14−0.87) 0.09 0.44 (0.16−1.00) 0.32
1.31−3.50 564 1.18 (0.53−2.48) 0.43 (0.14−1.43) 0.39 (0.16−0.94)
>3.50 514 1.18 (0.52−2.33) 0.33 (0.14−1.08) 0.30 (0.10−0.73)
missing 156 1.21 (0.68−2.26) 0.26 (0.14−0.84) 0.39 (0.21−0.83)
smoking
e
never smoker 1028 1.15 (0.54−2.36) 0.06 0.30 (0.14−1.04) 0.44 0.35 (0.12−0.81) 0.07
current smoker 365 1.43 (0.61−3.07) 0.40 (0.14−1.13) 0.45 (0.17−1.01)
ever smoker 415 1.33 (0.59−2.61) 0.40 (0.14−1.20) 0.35 (0.15−0.90)
Physical activity, MET
min/week
f
<600 767 1.15 (0.48−2.37) 0.84 0.38 (0.14−1.15) 0.99 0.36 (0.14−0.80) 0.81
600−1200 206 1.05 (0.56−2.11) 0.33 (0.14−1.23) 0.39 (0.12−1.02)
>1200 835 1.38 (0.65−2.65) 0.33 (0.14−0.98) 0.38 (0.14−0.88)
alcohol intake
g
nondrinker 1245 1.23 (0.54−2.47) 0.32 0.34 (0.14−1.17) 0.48 0.37 (0.14−0.85) 0.03
moderate drinker 136 1.25 (0.68−1.86) 0.41 (0.14−0.97) 0.26 (0.09−0.67)
heavy drinker 269 1.37 (0.63−2.93) 0.32 (0.14−1.10) 0.36 (0.16−1.05)
missing 158 1.04 (0.61−2.08) 0.34 (0.14−0.89) 0.50 (0.19−1.05)
a
All variables were adjusted using population weights for the sample in which BPA concentration was measured except N(unweighted sample size).
ANOVA was used to compare differences of urinary concentrations of BPA, BPF, and BPS among various categorical variables. The analysis of
creatinine-adjusted concentrations of BPA, BPS, and BPF is presented in Table S2, Supporting Information.
b
Race/ethnicity was categorized based
on self-reported data into Hispanic (including Mexican and non-Mexican Hispanic), non-Hispanic white, non-Hispanic black, and other race/
ethnicity.
37
c
Self-reported education was grouped as less than high school, high school, and college or higher.
37
d
Family IPRs were categorized as
≤1.30, 1.31−3.50, and >3.50.
37,50
e
Self-reported smoking was classified as never smokers who smoked less than 100 cigarettes in their lifetime;
current smokers who currently smoke cigarettes; and ever smokers who smoked more than 100 cigarettes in their lifetime but do not smoke
currently.
37
f
Self-reported physical activity was used to derive MET minutes per week according to the Global Physical Activity Questionnaire
Analysis Guide
71
and categorized as <600, 600−1200, and >1200 MET min/week.
37
g
Alcohol intake was categorized as non-drinker (0 g/day),
moderate drinker (0.1−28 g/day for men and 0.1−14 g/day for women), or heavy drinker (≥28 g/day for men and ≥28 g/day for women).
51
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Evidence from epidemiological and animal studies implicates
BPA in sex-specific adverse outcomes, including effects on the
brain, immune system, reproductive system, and metabolic
processes.
3,35,36
Significantly less information about potential
adverse health outcomes is available about BPF and BPS.
Exposure to BPF and BPS was not associated with obesity in
the general U.S. population; however, higher exposure to BPS
may be associated with greater body mass index and waist
circumference.
37
Urinary levels of both BPA and BPS were
strongly correlated with oxidative stress, as determined using 8-
hydroxy-2′-deoxyguanosine urine levels, in a population from
Saudi Arabia exposed highly to BPS.
38
BPA, but not BPF, was
positively associated with thyroid-stimulating hormone in a
case-control study from Cyprus and Romania investigating an
association between bisphenol exposure and thyroid nodular
disease.
39
Evidence from in vitro and in vivo laboratory studies
provides a mechanistic basis for a link between BPF and BPS
exposure and adverse health outcomes, such as obesity, in
humans: Similar to BPA, BPF and BPS are endocrine-
disrupting chemicals and display hormonal activity, with similar
average estrogenic, androgenic, and antiestrogenic potencies
across different in vitro assays.
40−42
Both BPF and BPS
differentially affect signaling pathways involved in lipid
metabolism and adipogenesis
43,44
and cause DNA damage.
42
Previous population-based studies with human biomonitor-
ing data have mainly focused on BPA. For BPA substitutes,
including BPF and BPS, available data were based on
convenience samples, rather than representative samples,
28,30
or focus on a specific, at-risk population, such as pregnant
women.
32
It is therefore imperative to know the current
exposure status of BPF and BPS in a sample that is
representative of the entire U.S. population, including children
and adolescents, and to characterize the difference in the levels
of these environmental phenols depending on population
characteristics and lifestyle factors. The present study, for the
first time, reports urinary levels of total BPA, BPF, and BPS in
the U.S. population by using the nationally representative data
from the National Health and Nutrition Examination Survey
(NHANES) 2013−2014. Demographic and lifestyle factors
associated with urinary levels of all three bisphenols were
analyzed as well. The results of this analysis demonstrate both
similarities and differences in contemporary exposure of the
U.S. population to BPA and its substitutes that warrant further
attention.
■RESULTS AND DISCUSSION
Detection Frequency and Levels of Urinary BPA, BPF,
and BPS. BPA was found in nearly all urine samples analyzed
as part of NHANES 2013−2014, with a detection frequency of
95.7%. This number is comparable to detection frequencies
reported in earlier studies of the general U.S. population.
26−28
The LODs for BPA in these earlier studies were comparable to
the LOD in this study and ranged from 0.1 to 0.4 μg/L.
Detection frequencies of BPA ranged from 74 to 99% in
archived urine samples from U.S. adults (N= 616) collected
between 2000 and 2014.
28
The lowest detection frequency in
this earlier study (74%) was observed in samples collected in
2014. In our study, detection frequencies of BPS and BPF were
89.4 and 66.5% in urine from U.S. adults, respectively. The
lower detection frequencies of both substitutes compared to
BPA are consistent with earlier, small-scale biomonitoring
studies in the U.S. and other countries.
28,30
The LODs for BPF
and BPS in the earlier studies were ≤0.1 μg/L.
28,30
In urine
samples collected in 2004−2005 from pregnant women from
the Netherlands (N= 1396), detection frequencies of BPA
(79.2%) were also higher compared to the detection
frequencies of BPS (67.8%) and BPF (40.2%).
32
Only limited
information regarding time trends in the levels of BPS and BPF
in humans is currently available. Detection frequencies for BPF
ranged from 42 to 88% in urine samples from U.S. adults
collected between 2000 and 2014 and showed no clear trend
with time.
28
In the same study, BPS had the lowest detection
frequencies (19−74%) of all three bisphenols. Unlike those of
BPF, detection frequencies of BPS in the urine from U.S. adults
increased from 2000 to 2014.
28
Because BPA, BPF, and BPS are
glucuronidated by human UGTs
20,21,53
and, as has been shown
for BPA, rapidly excreted with the urine,
23
their high detection
frequencies in spot urine samples from the NHANES
population indicate that the general U.S. population is
continuously exposed to all three bisphenols.
Median urinary levels of BPA in the adult U.S. population (N
= 1808) were 1.24 μg/L (interquartile range, 0.57−2.49 μg/L)
(Table 1). Median urinary levels of BPF and BPS were 0.35 μg/
L (0.14−1.11 μg/L) and 0.37 μg/L (0.14−0.88 μg/L),
respectively. For comparison, creatinine-adjusted median
urinary levels of BPA and its substitutes in adults were 1.20
μg/g creatinine (0.73−2.09 μg/g creatinine) for BPA, 0.46 μg/
g creatinine (0.21−1.06 μg/g creatinine) for BPF, and 0.39 μg/
g creatinine (0.21−0.84 μg/g creatinine) for BPS (Table S2).
The BPA levels observed in our analysis of NHANES 2013−
2014 data for the adult U.S. population are of the same order of
magnitude as the levels observed in other studies. For example,
a geometric mean BPA level of 2.6 μg/L has been reported for
the NHANES 2003−2004 cycle.
26
An examination of
convenience urine samples of U.S. adults showed a significant
decrease in urinary levels of total BPA from 2.07 μg/L in 2010
to 0.36 μg/L in 2014,
28
which is consistent with the global
phaseout of BPA in food packaging, thermal paper, and other
consumer products that contribute to human exposure.
54,55
Urinary levels of BPA in the NHANES 2013−2014 population
are also within the range of concentrations reported for several
other countries. For example, the 2007−2009 Canadian Health
Measures Survey reported geometric mean urinary BPA levels
ranging from 0.82 to 1.49 μg/L for the adult Canadian
population.
56
Geometric mean levels of BPA in urine samples
collected from 2010 to 2013 in several European and Asian
countries ranged from 0.84 μg/L in Japan to 1.59 μg/L in
India.
31,57,58
In a study of pregnant women from the
Netherlands, median levels of BPA were 1.66 μg/L (0.72−
3.56 μg/L) in urine samples collected in 2004−2005 (N=
1396).
32
Levels of 2.99 μg/L (0.233−27.6 μg/L; N= 116) were
reported for a more highly exposed population living near an E-
waste-dismantling area in China.
59
Information about urinary levels of BPF and BPS is much
more limited compared to that of BPA. A study in pregnant
women from the Netherlands reported median levels of 0.36
μg/L (0.17−1.08 μg/L; N= 1396) for BPS and 0.57 μg/L for
BPF (0.30−1.29 μg/L; N= 1396).
32
Median BPF levels of
0.365 μg/L (<LOD to 8.68 μg/L; N= 116) were observed in a
Chinese population living near an E-waste-dismantling area.
59
These levels are comparable to the levels observed in the adult
NHANES 2013−2014 population in this study (Table 1).
Median BPS levels in this study (0.37 μg/L) were higher than
BPS levels (median 0.191 μg/L, <LOD to 21.0 μg/L; N= 315)
observed in urine samples collected from 2010 to 2011 in
several Asian countries, including China, India, Korea, Kuwait,
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Malaysia, and Vietnam.
30
Some studies report higher urinary
BPS levels compared to the NHANES 2013−2014 data. For
example, median levels of BPS were 1.04 μg/L (N= 36) in
urine from Japan
30
and 4.92 μg/L (N= 130) in urine from
Saudi Arabia.
38
Although these two studies only investigated a
small number of individuals, these findings indicate that,
compared to the US, some countries may have significantly
higher exposures to BPS because of unique, country-specific
environmental factors and consumer behaviors. In the adult
U.S. population, BPS showed a slight increase in detection
frequency and geometric mean concentration in urine from not
calculated in 2010 to 0.25 μg/L in 2014.
28
This finding is not
surprising because of the replacement of BPA with BPS and
other bisphenols in various consumer products. Interestingly,
no clear time trend was observed for urinary levels of BPF,
28
possibly because of the low detection frequency on BPF in
urine or because BPF is a natural product present in foodstuff,
in particular mustard.
12
Age, Gender, and Race/Ethnic Differences in Urinary
BPA, BPF, and BPS Concentrations in U.S. Adults. BPA
levels differed significantly between age groups (P< 0.001;
Table 1); however, no significant differences were observed in
the linear regression analysis (Table 2). Urinary levels of BPA
showed a trend to increase with age in adult Koreans, with 60−
69 year old Korean adults having the highest BPA levels,
60
whereas a decrease in urinary BPA concentrations with age has
been reported for the NHANES 2005−2006 population.
17
Several other biomonitoring studies reported no association
between levels of bisphenols in adults and age.
32,60−62
Overall,
associations between urinary levels of BPA and, possibly, its
substitutes and age appear to vary in different adult populations,
suggesting that more complex environmental factors contribute
to adult exposures. Moreover, exposure patterns may change in
a population, as suggested by the different age trends of BPA
levels observed in the NHANES 2005−2006
17
versus
NHANES 2013−2014 data (this study).
Urinary levels of BPA (P= 0.002) and BPF (P= 0.03) were
significantly higher in urine samples from male compared to
female adults (Table 1). BPS levels were also higher in men
than in women; however, this difference did not reach statistical
significance (P= 0.08). Gender-related differences in urinary
levels did not reach statistical significance in the linear
regression analysis for any bisphenol investigated (Table 2).
Similarly, biomonitoring studies from across the world
consistently report that geometric mean urinary levels of BPA
in men are higher compared to women; however, these
Table 2. Association of Demographic and Lifestyle Factors in Adults (N= 1808) from NHANES 2013−2014 with Urinary BPA,
BPF, and BPS Concentrations
a
BPA BPF BPS
variable βcoefficient Pβcoefficient Pβcoefficient P
age 20−39 [ref] [ref] [ref]
40−59 −0.02 0.80 −0.02 0.84 0.02 0.8
≥60 0.03 0.65 0.003 0.98 0.18 0.1
gender male [ref] [ref] [ref]
female 0.07 0.20 0.005 0.95 0.05 0.55
race/ethnicity
b
non-Hispanic white [ref] [ref] [ref]
Hispanic 0.01 0.91 −0.34 0.10 0.23 0.02
non-Hispanic black 0.08 0.10 −0.09 0.43 0.35 0.005
other −0.07 0.42 −0.31 0.06 0.14 0.24
education
c
less than high school [ref] [ref] [ref]
high school 0.001 0.99 0.10 0.45 −0.04 0.61
college or higher −0.07 0.45 −0.05 0.73 −0.10 0.32
family IPR
d
≤1.30 [ref] [ref] [ref]
1.31−3.50 −0.10 0.09 0.30 0.02 0.04 0.69
>3.50 −0.14 0.01 0.18 0.054 −0.05 0.65
missing −0.08 0.53 0.11 0.61 0.10 0.52
smoking
e
never smoker [ref] [ref] [ref]
current smoker 0.19 0.01 0.13 0.45 0.13 0.07
ever smoker 0.12 0.09 0.16 0.23 0.11 0.16
physical activity, MET min/week
f
<600 [ref] [ref] [ref]
600−1200 0.02 0.75 0.07 0.56 0.01 0.93
>1200 0.14 0.02 −0.07 0.33 0.01 0.91
alcohol intake
g
nondrinker [ref] [ref] [ref]
moderate drinker −0.02 0.82 −0.07 0.51 −0.29 0.004
heavy drinker 0.07 0.30 −0.21 0.29 0.10 0.26
missing −0.19 0.02 −0.005 0.99 0.16 0.10
a
The analysis of creatinine-adjusted concentrations of BPA, BPS, and BPF is presented in Table S3, Supporting Information.
b
Race/ethnicity was
categorized based on self-reported data into Hispanic (including Mexican and non-Mexican Hispanic), non-Hispanic white, non-Hispanic black, and
other race/ethnicity.
37
c
Self-reported education was grouped as less than high school, high school, and college or higher.
37
d
Family IPRs were
categorized as ≤1.30, 1.30−3.50, and >3.50.
37,50
e
Self-reported smoking was classified as never smokers who smoked less than 100 cigarettes in their
lifetime; current smokers who currently smoke cigarettes; and ever smokers who smoked more than 100 cigarettes in their lifetime but do not smoke
currently.
37
f
Self-reported physical activity was used to derive MET minutes per week according to the Global Physical Activity Questionnaire
Analysis Guide
71
and categorized as <600, 600−1200, and >1200 MET min/week.
37
g
Alcohol intake was categorized as non-drinker (0 g/day),
moderate drinker (0.1−28 g/day for men and 0.1−14 g/day for women), or heavy drinker (≥28 g/day for men and ≥28 g/day for women).
51
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differences were frequently not statistically signifi-
cant.
26,56,58,61−63
Only limited information about gender
differences in urinary BPF and BPS levels is available. A
biomonitoring study in several Asian countries versus the U.S.
observed higher geometric mean levels of BPS in men versus
women (0.239 μg/L vs 0.126 μg/L, respectively); however, this
difference did not reach statistical significance in the entire
study population.
30
It is noteworthy that men have slightly higher estimated daily
intakes of BPA than women based on an analysis of the
NHANES 2005−2006 data.
17
It is currently unknown if there
are gender differences in the daily intake of BPF and BPS. In
addition to differences in exposures, gender differences in the
toxicokinetics of the bisphenols investigated could contribute to
gender differences in urinary levels of bisphenols. For example,
gender differences in the hepatic expression of UGTs, including
the major BPA metabolizing isoform UGB2B15, and other
human drug-metabolizing enzymes are well established.
64
Indeed, gender differences in BPA metabolism have been
reported for BPA in a small number of Korean adults, with
higher urinary levels of the BPA glucuronide in males, but
higher levels of the BPA sulfate in females.
65
However, these
differences in specific BPA conjugates did not translate into
significant differences in urinary BPA levels by gender in the
Korean study population.
Statistically significant race/ethnicity-dependent differences
were observed for BPA (P= 0.007) only in the analysis of
variance (ANOVA) (Tables 1 vs 2). An earlier analysis of data
from NHANES 2003−2004 revealed significant differences by
race/ethnicity, with lower least-squares geometric mean levels
observed in Mexican Americans than non-Hispanic whites and
non-Hispanic blacks.
26
The earlier finding that levels of BPA
are lower in Mexican Americans in the NHANES 2003−2004
population is consistent with results from a German
biomonitoring study reporting lower levels in children from
families with a migration background.
66
Significant race/
ethnicity-dependent differences in urinary levels were also
observed for BPS (P= 0.001, Table 1). These findings were
confirmed in the linear regression analysis, where urinary levels
of BPS in Hispanics (βcoefficient 0.23, P= 0.02) and non-
Hispanic blacks (βcoefficient 0.35, P=0.005)were
significantly different compared to non-Hispanic white (Table
2). A small biomonitoring study investigated an association
between race/ethnicity and urinary BPS levels in a small
population of mostly Caucasians and Asians from Albany, New
York.
30
This study found higher levels of BPS in Caucasians
versus Asians; however, this difference did not reach statistical
significance. A recent study reported lower BPS levels in
pregnant women of non-European descent living in the
NetherlandscomparedtoDutchwomenofEuropean
descent.
32
Factors Affecting Urinary Levels of BPA and Its
Substitutes in U.S. Adults. In the linear regression analysis
(Table 2), the income-to-poverty ratio (IPR) was associated
with urinary BPA levels in the adult NHANES 2013−2014
population, with lower BPA levels being detected in individuals
from the high versus low IPR group (βcoefficient −0.14 and P
= 0.01). Levels of BPF were also significantly different between
the medium versus low IPR group (βcoefficient 0.30 and P=
0.02). Interestingly, levels of BPF appeared to be higher in the
group with a medium family income compared to that with a
low family income. Similar to our findings, an earlier analysis of
NHANES 2003−2004 data revealed an association between
family income and urinary BPA levels.
26
Income was also
significantly associated with urinary BPA levels in Korea, with
the lowest levels observed in the highest income group,
67
whereas no associations were observed in an earlier study of
Korean adults.
60
A biomonitoring study in Germany found no
correlation between the socioeconomic status, which includes
household income, and BPA exposure levels.
66
Similarly,
urinary BPA levels were not significantly associated with
income in the 2007−2009 Canadian Health Measures Survey;
however, the least-squares geometric mean BPA level of the
third quartile income group was significantly higher compared
to that of the fourth quartile income group.
56
These limited
studies suggest that, at the time of each study, household
income is linked to region- or country-specific factors that affect
exposure to specific bisphenols. For example, the findings from
our analysis of the NHANES 2013−2014 data raise the
question if differences in BPA versus BPF exposures by
Table 3. Urinary Concentrations of BPA, BPF, and BPS in U.S. Children in NHANES 2013−2014
a
BPA, μg/L BPF, μg/L BPS, μg/L
variable Nmedian (P25−P75) Pmedian (P25−P75) Pmedian (P25−P75) P
all 868 1.25 (0.64−2.42) 0.32 (0.14−0.99) 0.29 (0.12−0.70)
age 6−11 years 409 1.34 (0.70−2.72) 0.051 0.27 (0.14−0.85) 0.009 0.27 (0.12−0.64) 0.18
12−19 years 459 1.14 (0.60−2.30) 0.37 (0.14−1.10) 0.30 (0.13−0.77)
gender male 429 1.22 (0.66−2.38) 0.97 0.30 (0.14−1.03) 0.83 0.28 (0.12−0.63) 0.21
female 439 1.27 (0.64−2.49) 0.33 (0.14−0.97) 0.30 (0.13−0.78)
race/ethnicity
b
non-Hispanic white 229 1.23 (0.61−2.14) 0.18 0.40 (0.14−1.23) 0.007 0.24 (0.11−0.60) 0.02
Hispanic 286 1.13 (0.63−2.33) 0.24 (0.14−0.64) 0.39 (0.15−0.99)
non-Hispanic black 223 1.84 (0.98−3.22) 0.36 (0.14−0.95) 0.36 (0.17−0.75)
other 130 1.09 (0.61−2.32) 0.17 (0.14−0.93) 0.29 (0.13−0.71)
family IPR
c
≤1.30 406 1.32 (0.76−2.55) 0.76 0.25 (0.14−0.79) 0.03 0.30 (0.11−0.70) 0.45
1.31−3.50 236 1.36 (0.69−2.53) 0.34 (0.14−1.22) 0.27 (0.13−0.74)
>3.50 154 1.09 (0.58−2.16) 0.39 (0.14−1.10) 0.27 (0.12−0.58)
missing 72 1.00 (0.47−1.55) 0.25 (0.14−0.74) 0.45 (0.19−1.05)
a
All variables were adjusted using population weights for the sample in which BPA concentration was measured except N(unweighted sample size).
ANOVA was used to compare differences of urinary concentrations of BPA, BPF, and BPS among various categorical variables. The analysis of
creatinine-adjusted concentrations of BPA, BPS, and BPF is presented in Table S4, Supporting Information.
b
Race/ethnicity was categorized based
on self-reported data into Hispanic (including Mexican and non-Mexican Hispanic), non-Hispanic white, non-Hispanic black, and other race/
ethnicity.
37
c
Family IPRs were categorized as ≤1.30, 1.31−3.50, and >3.50.
37,50
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household income reflect a shift from using BPA to BPA-free
(but BPF-containing) consumer products in more affluent U.S.
households.
Linear regression analysis revealed that urinary levels of BPA
(βcoefficient 0.19 and P= 0.01) were higher in current
smokers compared with adults who never smoked (Table 2).
Higher urinary BPA levels have also been observed in Chinese
smokers.
62
Similarly, women who smoked during pregnancy
had higher environmental bisphenol levels in urine in a
biomonitoring study from the Netherlands.
32
Smoking was not
associated with BPA levels in the NHANES 2003−2004 data
26
and in Korean adults.
60,67,68
A negative association between
smoking and BPA levels has been reported for the NHANES
2005−2006 population.
17
Although smoking affects the
expression of drug-processing genes in the intestine and the
liver, these changes are expected to increase the expression of
drug-processing genes involved in the metabolism of BPA and
its substitutes and, consequently, do not explain higher BPA
levels in smokers. It is more likely that smoking is a surrogate
for other factors associated with exposure to bisphenols.
17
Statistically significant differences based on alcohol intake
were observed for BPS in ANOVA (P= 0.03, Table 1).
Moreover, in the linear regression analysis, alcohol intake was
associated with urinary BPS levels, with alcohol intake being
significantly different between the moderate drinker and non-
drinker groups (βcoefficient −0.29 and P= 0.004, Table 2). In
addition, physical activity was associated with urinary BPA
levels (βcoefficient 0.14 and P= 0.02, Table 2) in the linear
regression analysis. It is currently unclear why these lifestyle
factors are associated with urinary levels of specific bisphenols.
As for smoking, these factors may be surrogates for
physiological or lifestyle factors affecting exposures to
bisphenols and further studies are needed to better characterize
these factors.
Urinary Concentrations of BPA and Its Substitutes in
U.S. Children and Adolescents. Median bisphenol concen-
trations in U.S. children (6−11 years old) were 1.34 μg/L
(0.70−2.72 μg/L; N= 409) for BPA, 0.27 μg/L (0.14−0.85
μg/L) for BPF, and 0.27 μg/L (0.12−0.64 μg/L) for BPS
(Table 3). For comparison, creatinine-adjusted median urinary
levels of BPA and its substitutes in children were 1.80 μg/g
creatinine (1.05−3.08 μg/g creatinine) for BPA, 0.45 μg/g
creatinine (0.19−1.18 μg/g creatinine) for BPF, and 0.40 μg/g
creatinine (0.21−0.78 μg/g creatinine) for BPS (Table S4).
Adolescents (12−19 years) in the NHANES 2013−2014
population (N= 459) had urinary levels of 1.14 μg/L (0.60−
2.30 μg/L) for BPA, 0.37 μg/L (0.14−1.10 μg/L) for BPF, and
0.30 μg/L (0.13−0.77 μg/L) for BPS (Table 3). In this age
group, creatinine-adjusted levels were 0.93 μg/g creatinine
(0.60−1.71 μg/g creatinine), 0.38 μg/g creatinine (0.15−1.04
μg/g creatinine), and 0.29 (0.16−0.58 μg/g creatinine) for
BPA, BPF, and BPS, respectively (Table S4).
Children had higher median BPA levels compared to
adolescents (P= 0.051; Table 3), a difference that reached
statistical significance in the linear regression analysis (β
coefficient −0.40 and P< 0.0001; Table 4). The opposite trend
was observed for urinary BPF levels in children; however, this
difference was not statistically significant in the linear regression
analysis. Urinary BPS levels were not significantly different
between both age groups. An earlier analysis of the NHANES
2003−2004 data revealed a decrease in urinary levels of BPA
from children to adolescents to adults.
26
Human biomonitoring
studies from different parts of the world consistently report
higher urinary levels of BPA in children than in adults.
58,63,67,69
BPS levels were also higher in adolescents than in adults in a
study of human exposures to BPS in Asia and the U.S.
30
These
earlier findings are consistent with a higher xenobiotic intake of
children and adolescents compared to adults due to a higher
food intake and respiratory rate compared to adults; exposure
to bisphenols via ingestion of household dust; more (dermal)
contact with products containing BPA or its substitutes; and
differences in the absorption, distribution, metabolism, and
excretion of xenobiotics between children and adults. It is
important to note that urinary levels of BPA were significantly
higher in children compared to adults in the NHANES 2003−
2004 population,
26
whereas median urinary levels of BPA in
young adults (20−39 years old) were higher compared to those
in children (6−11 years old) in the NHANES 2013−2014
population (1.47 vs 1.34 μg/L), possibly because of the ban of
BPA in certain consumer products in the United States and
other countries.
In the linear regression analysis, gender was associated with
BPS levels, but not with BPA and BPF levels, in children (β
coefficient 0.16, P= 0.045; Table 4). BPS levels were higher in
Table 4. Association of Demographic Factors in Children (N= 868) from NHANES 2013−2014 with Urinary BPA, BPF, and
BPS Concentrations
a
BPA BPF BPS
variable βcoefficient Pβcoefficient Pβcoefficient P
age 6−11 [ref] [ref] [ref]
12−19 −0.40 <0.0001 0.06 0.56 −0.16 0.055
gender male [ref] [ref] [ref]
female 0.07 0.24 0.11 0.50 0.16 0.045
race/ethnicity
b
non-Hispanic white [ref] [ref] [ref]
Hispanic −0.023 0.75 −0.39 0.001 0.35 0.03
non-Hispanic black 0.16 0.18 −0.16 0.40 0.17 0.29
other −0.008 0.95 −0.28 0.13 0.14 0.19
family IPR
c
≤1.30 [ref] [ref] [ref]
1.31−3.50 −0.13 0.13 0.07 0.55 0.04 0.77
>3.50 −0.27 0.053 0.08 0.53 −0.09 0.42
missing −0.43 0.002 −0.26 0.13 0.38 0.01
a
The analysis of creatinine-adjusted concentrations of BPA, BPS, and BPF is presented in Table S5, Supporting Information.
b
Race/ethnicity was
categorized based on self-reported data into Hispanic (including Mexican and non-Mexican Hispanic), non-Hispanic white, non-Hispanic black, and
other race/ethnicity.
37
c
Family IPRs were categorized as ≤1.30, 1.31−3.50, and >3.50.
37,50
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female children compared to male children. Significant
differences based on race/ethnicity were observed for urinary
BPF (P= 0.007) and BPS (P= 0.02) (Table 3). In the linear
regression analysis (Table 4), BPF levels were significantly
lower in Hispanic children compared to non-Hispanic whites
(βcoefficient −0.39, P= 0.001). The opposite trend was
observed for BPS levels, with higher urinary BPS levels being
observed in Hispanic compared to non-Hispanic white children
(βcoefficient 0.35, P= 0.03). Urinary levels of BPF (P= 0.03)
in children were associated with family income in ANOVA
(Table 3). As for the adult NHANES 2013−2014 population
(Table 2), linear regression showed a negative association
between BPA levels in children and family incomes, whereby
children from the high-family income group had a lower urinary
level of BPA compared to those from the low-family income
group (βcoefficient −0.27, P= 0.053; Table 4). These results
demonstrate that complex social, economic, and environmental
factors modulate the exposure of children and adolescents to
bisphenols.
Human Health Implications. Bisphenols are ubiquitous
environmental pollutants,
9
and as indicated by the high
detection frequencies in this study, both U.S. adults and
children are continuously exposed to these environmental
pollutants. Exposure patters for BPA across age groups have
changed over time, with children and adolescents having lower
exposures relative to adults in NHANES 2013−2014,
suggesting that the replacement of BPA, especially in food
contact materials, has resulted in a reduction of human
exposures to BPA. However, exposures to other bisphenols,
in particular BPS, are growing human health concerns not only
because of the high detection frequency but also because of
emerging evidence that BPS, but not BPF, exposures increase in
the U.S. population.
28
It is important to note that the
associations between demographic and lifestyle factors and
urinary levels of bisphenols observed in this analysis of the
NHANES 2013−2014 data are complex and cannot be easily
explained by the same routes of exposure; that is, findings for
BPA cannot be simply applied to other bisphenols. Because of
the ubiquitous exposure of the U.S. population to BPA, BPF,
and BPS, more research is therefore needed to characterize the
routes of exposure in different segments of the U.S. population
and, ultimately, identify modifiable factors to reduce human
exposures to specific bisphenols.
■EXPERIMENTAL SECTION
NHANES Overview. NHANES is a nationally representa-
tive survey of the noninstitutionalized civilian resident
population of the United States.
45
NHANES data are released
by the Centers for Disease Control and Prevention in 2 year
cycles. Participants are selected using census data based on their
age, gender, and racial/ethnic background through a multistage
probability sampling design. NHANES collects extensive data
through questionnaires and physical examinations to assess the
health and nutritional status of the general U.S. population.
Moreover, human biospecimens, such as blood and urine
samples, are collected for laboratory tests during each cycle,
including the measurements of environmental pollutants.
NHANES is reviewed and approved by the National Center
for Health Statistics Institutional Review Board, and written
informed consent is obtained from all participants. A detailed
description of NHANES is available elsewhere.
46
For this study, we analyzed data from the NHANES 2013−
2014 cycle (see Table S1 for the sources of the data). BPS and
BPF exposure of the U.S. population was evaluated for the first
time in this cycle, although BPA exposure has been assessed in
earlier cycles.
26
The participants of NHANES 2013−2014 (n=
10 175) included 4406 children and 5769 adults. A one-third
subsample of participants aged 6 years or older was randomly
selected for the measurements of BPA, BPS, and BPF in spot
urine samples. Ultimately, 2676 participants were included in
our analysis of the NHANES 2013−2014 data after excluding
those with missing data on urinary BPA, BPS, or BPF
concentrations.
Analysis of Total Urinary Levels of BPA, BPF, and BPS.
Total urinary levels of BPA, BPF, and BPS were measured at
the Division of Laboratory Sciences, National Center for
Environmental Health, Centers for Disease Control and
Prevention, using published procedures. Briefly, the total
concentration (free and conjugated) of the target analytes in
urine samples was measured after deconjugation at 37 °C for 4
h with β-glucuronidase/sulfatase (4 mg/mL; 463 000 U/g solid
in 1 M ammonium acetate buffer at pH 5; Sigma-Aldrich
Laboratories, St. Louis, MO, USA). The extent of the
deconjugation reaction was assessed by adding a deconjugation
standard solution containing 4-methylumbelliferyl glucuronide,
4-methylumbelliferyl sulfate, and 13C4-4-methylumbelliferone
(500 ng/mL each; Cambridge Isotope Laboratories, Tewks-
bury, MA, USA) to all incubation mixtures and monitoring the
4-methylumbelliferone/13C4-4-methylumbelliferone peak area
ratio after sample incubation as reported previously.
47−49
An
area count ratio >0.4 was considered acceptable for the
deconjugation reaction of unknown samples.
49
Total BPA, BPF,
and BPS were quantified after deconjugation by on-line solid-
phase extraction (SPE)−high-performance liquid chromatog-
raphy (HPLC) with atmospheric pressure chemical ionization
(APCI)−mass spectrometry (MS)/MS in the negative-ion
APCI mode. Details of the on-line SPE−HPLC−MS/MS
system and the instrument parameters have been reported
previously.
47,48
The LODs were 0.2 μg/L for BPA, 0.2 μg/L for
BPF, and 0.1 μg/L for BPS. For analytes with levels below the
LOD, an imputed fill value was assigned as the LOD divided by
the square root of 2. All analyses were accompanied by quality
assurance/quality control samples to account for any possible
background contamination of the sampling materials with
bisphenols.
49
Specifically, the calculated concentrations of the
target analytes in the reagent blanks were less than three times
the LOD. Moreover, all standards, blanks, and unknown
samples were prepared following the same procedure; thus, the
background, represented as the intercept of the calibration
curve, was automatically subtracted during the quantification of
all analytes. In addition to the reagent blanks, two empty vials
were also included with each batch to check for potential
background contamination.
Demographic and Lifestyle Factors. Information on
demographic (i.e., age, gender, race/ethnicity, education, and
family income) and lifestyle factors (i.e., physical activity,
smoking status, and alcohol intake) of study participants was
collected using standardized questionnaires. Race/ethnicity was
categorized based on self-reported data into Hispanic
(including Mexican and non-Mexican Hispanic), non-Hispanic
white, non-Hispanic black, and other race/ethnicity.
37
Family
IPRs were categorized as ≤1.30, 1.31−3.50, and >3.50 based on
the cutoffpoints of the Supplemental Nutrition Assistance
Program.
37,50
In accordance with the NHANES Analytic
Guidelines,
70
individuals who smoked less than 100 cigarettes
in their lifetime were defined as never smokers; those who
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smoked more than 100 cigarettes but do not smoke currently
were considered ever smokers; and those who currently smoke
cigarettes were classified as current smokers. Alcohol intake was
categorized as 0, 0.1−28, and ≥28 g/day for men and 0, 0.1−
14, and ≥14 g/day for women.
51
Self-reported physical activity
was used to derive metabolic equivalent of task (MET) minutes
per week and categorized as <600, 600−1200, and >1200 MET
min/week.
37
A summary of the characteristics of the study
participants is provided in Table 5.
Statistical Analyses. The NHANES uses a complex,
multistage probability sampling design to represent the civilian,
noninstitutionalized U.S. population. Therefore, appropriate
published sample weights were applied to account for the
differential probability of selection, nonresponse adjustment,
and adjustment to independent population controls. The
Taylor series linearization method was used for variance
estimation to account for stratification and clustering, following
the NHANES Analytic Guidelines.
70
We used ANOVA to compare differences of urinary
concentrations of BPA, BPF, and BPS (log transformed)
among various categorical variables. We conducted linear
regression analyses by including all variables simultaneously in
the model to detect independent effects of each variable.
Urinary creatinine levels were adjusted in the model as
previously recommended to account for urine dilution.
52
To
facilitate a comparison with other studies, we also report
analogous analyses of urinary bisphenol levels adjusted for
creatinine in the Supporting Information (Tables S2 to S5). All
statistical analyses were performed with SAS software (version
9.4; SAS Institute). P< 0.05 was considered statistically
significant.
■ASSOCIATED CONTENT
*
SSupporting Information
The Supporting Information is available free of charge on the
ACS Publications website at DOI: 10.1021/acsomega.8b00824.
File names and URLs of the original data and analyses of
associations of creatinine-adjusted urinary levels of BPA,
BPF, and BPS with various demographic factors in the
NHANES 2013−2014 population (PDF)
■AUTHOR INFORMATION
Corresponding Author
*E-mail: wei-bao@uiowa.edu. Phone: 319-384-1546. Fax: 319-
384-4155 (W.B.).
ORCID
Hans-Joachim Lehmler: 0000-0001-9163-927X
Wei Bao: 0000-0002-7301-5786
Notes
The authors declare no competing financial interest.
■ACKNOWLEDGMENTS
This study was supported by the National Institute of
Environmental Health Sciences/National Institutes of Health
[P30 ES005605]. The findings and conclusions in this
manuscript are those of the authors and do not necessarily
represent the views of the National Institute of Environmental
Health Sciences/National Institutes of Health.
■REFERENCES
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(2) Milner, L. Chemical Profiles; ICIS Chemical Business, 2017; p 1.
(3) Tsai, W. T. Human health risk on environmental exposure to
Bisphenol-A: a review. J. Environ. Sci. Health, Part C: Environ. Carcinog.
Ecotoxicol. Rev. 2006,24, 225−255.
(4) FDA (Food and Drug Administration). 2014. Bisphenol A
(BPA): Use in food contact application. Available https://www.fda.
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(5) European Commission. 2011. Bisphenol A: EU ban on baby
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rapid/press-release_IP-11-664_en.htm (accessed May 4, 2018).
(6) Government of Canada. 2016. Bisphenol A (BPA). Available
https://www.canada.ca/en/health-canada/services/home-garden-
safety/bisphenol-bpa.html (accessed May 4, 2018).
(7) Hormann, A. M.; Vom Saal, F. S.; Nagel, S. C.; Stahlhut, R. W.;
Moyer, C. L.; Ellersieck, M. R.; Welshons, W. V.; Toutain, P.-L.;
Taylor, J. A. Holding thermal receipt paper and eating food after using
hand sanitizer results in high serum bioactive and urine total levels of
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(8) European Chemicals Agency. Available https://echa.europa.eu/
information-on-chemicals/registered-substances (accessed May 4,
2018).
Table 5. Subject Demographics and Characteristics (N= 2676)
a
age, years
characteristics 6−11 12−19 20−39 40−59 ≥60
number of participants 409 459 598 607 603
gender, % (SE) male 50.11 (3.80) 51.00 (2.37) 49.63 (2.58) 49.30 (2.73) 45.81 (2.84)
female 49.88 (3.80) 49.00 (2.37) 50.37 (2.58) 50.70 (2.73) 54.19 (2.84)
race/ethnicity,
b
% (SE) non-Hispanic white 51.12 (5.53) 54.11 (4.70) 56.67 (4.47) 65.83 (3.40) 77.61 (3.50)
Hispanic 24.31 (3.93) 22.23 (3.95) 20.61 (3.06) 14.15 (2.61) 7.88 (1.94)
non-Hispanic black 13.59 (2.32) 14.92 (2.21) 12.83 (2.16) 11.60 (1.75) 8.97 (1.92)
other 10.98 (2.25) 8.73 (1.50) 9.90 (1.55) 8.42 (1.25) 5.55 (1.07)
family IPR,
c
% (SE) ≤1.30 38.03 (4.53) 32.57 (3.64) 31.03 (2.74) 20.34 (3.93) 17.12 (1.87)
1.31−3.50 30.18 (2.32) 31.92 (3.56) 34.23 (2.64) 28.35 (2.64) 35.32 (2.47)
>3.50 25.38 (5.09) 28.19 (2.77) 27.12 (2.54) 43.38 (3.97) 39.77 (3.03)
missing 6.41 (1.64) 7.32 (1.67) 7.62 (1.59) 7.93 (1.35) 7.79 (1.55)
a
All variables were adjusted using population weights for the sample in which BPA concentrations were measured except the number of participants
(SE, standard error). All estimates were weighted.
b
Race/ethnicity was categorized based on self-reported data into Hispanic (including Mexican and
non-Mexican Hispanic), non-Hispanic white, non-Hispanic black, and other race/ethnicity.
37
c
Family IPRs were categorized as ≤1.30, 1.31−3.50,
and >3.50.
37,50
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