PBDE flame retardants, thyroid disease, and menopausal status in U.S. women
Allen et al. Environmental Health
PBDE flame retardants, thyroid disease, and menopausal status in U.S. women
Joseph G. Allen 0
Sara Gale 0
R. Thomas Zoeller 2
John D. Spengler 0
Linda Birnbaum 1
Eileen McNeely 0
0 Department of Environmental Health, Harvard T. H. Chan School of Public Health , 401 Park Drive, Boston, MA 02215 , USA
1 National Cancer Institute/NIEHS , Research Triangle Park, NC , USA
2 University of Massachusetts Amherst , Amherst, MA , USA
Background: Women have elevated rates of thyroid disease compared to men. Environmental toxicants have been implicated as contributors to this dimorphism, including polybrominated diphenyl ethers (PBDEs), flame retardant chemicals that disrupt thyroid hormone action. PBDEs have also been implicated in the disruption of estrogenic activity, and estrogen levels regulate thyroid hormones. Post-menopausal women may therefore be particularly vulnerable to PBDE induced thyroid effects, given low estrogen reserves. The objective of this study was to test for an association between serum PBDE concentrations and thyroid disease in women from the United States (U.S.), stratified by menopause status. Methods: Serum PBDE concentrations (BDEs 47, 99, 100 and 153) from the National Health and Examination Survey (NHANES) and reports on thyroid problems were available in the NHANES 2003-2004 cycle. Odds ratios (ORs) were calculated using multivariate logistic regression models accounting for population-weighted survey techniques and controlling for age, body mass index (BMI), education, smoking, alcohol consumption and thyroid medication. Menopause status was obtained by self-reported absence of menstruation in the previous 12 months and declared menopause. Results: Women in the highest quartile of serum concentrations for BDEs 47, 99, and 100 had increased odds of currently having thyroid disease (ORs: 1.5, 1.8, 1.5, respectively) compared to the reference group (1st and 2nd quartiles combined); stronger associations were observed when the analysis was restricted to postmenopausal women (ORs: 2.2, 3.6, 2.0, respectively). Conclusion: Exposure to BDEs 47, 99, and 100 is associated with thyroid disease in a national sample of U.S. women, with greater effects observed post-menopause, suggesting that the disruption of thyroid signaling by PBDEs may be enhanced by the altered estrogen levels during menopause.
Endocrine disruptors; Polybrominated diphenyl ethers; PBDE; Thyroid; Menopause
Fire safety standards promulgated in California in the late
1970’s have led to the proliferation of chemical flame
retardants (FRs) used in consumer products worldwide [
Brominated flame retardant compounds are used as
additives in products at up to 20 % by weight of the product
]. Precisely because they are used as additives, rather
than covalently bound to a polymer matrix, these
halogenated FRs can and do migrate from their source products
into the indoor and outdoor environment [
]. In fact, the
global use of one class of environmentally-persistent flame
retardant chemicals over a 35-year period,
polybrominated diphenyl ethers (PBDEs), has led to their near
ubiquitous presence in animals, abiotic matrices and
food, as well as in air, dust and surfaces of indoor
PBDEs share a similar structure to polychlorinated
biphenyls (PCBs), polybrominated biphenyls (PBBs),
tetrabromobisphenol A (TBBPA), triclosan, and the
halogenatedphenyl ring of thyroid hormone thyroxine (T4), with the
potential for 209 different congeners based on the
number and position of the bromine within the aromatic
rings. PBDEs were manufactured in three commercial
products—PentaBDE, OctaBDE, DecaBDE—each of
which is dominated by one or more congeners (BDEs 47
(2,2′4,4′-tetra-bromodiphenyl ether), 99
(2,2′4,4′5-pentabromodiphenyl ether), 100 (2,2′,4,4′,6-penta-bromodiphenyl
ether); BDE 183 (2,2′,3,4,4′,5′,6-hepta-bromodiphenly ether);
BDE 209 (deca-bromodiphenyl ether), respectively). The
use of PBDEs as flame retardants have been phased out or
banned in some countries, and updated California fire
safety standards no longer require PBDEs or other flame
retardant chemicals to be used in furniture [
exposure is expected to continue for several decades
because of the reservoir of these chemicals that exist in
consumer products that have long durations of use (e.g.
couches), and the environmental stability of PBDEs. The
most recent data available from NHANES shows that a
reduction in PBDEs in serum was not yet observed on a
national level following the phase-out of several PBDEs in
], although more current biomonitoring data
suggest that levels are decreasing [
We have known for over 20 years that some PBDEs
are carcinogenic. A study by the National Toxicology
Program reported in 1986 found that DecaBDE causes
thyroid and liver tumors in rats and mice [
recently, a NTP study on PBDEs found that DE71, the
major commercial mixture of PentaBDE, is a two-species,
two-sex carcinogen [
]. Epidemiological evidence
demonstrates that PBDEs are also endocrine-disrupting
compounds that interfere with thyroid hormone action
], reproduction, and neurodevelopment [
changes in circulating thyroid hormone concentrations
(e.g., free and total T3 (triiodothyronine), T4, TSH
(thyroid stimulating hormone)) are associated with many
adverse health effects. Thyroid hormones regulate the
growth and differentiation of the brain and are therefore
critical for neurodevelopment ; the developing fetus
relies on maternal thyroid hormone until week 11 of
] before beginning to produce endogenous
hormones, and doesn’t produce sufficient hormone for its
own needs until approximately week 20 [
because the thyroid is a modulator for many of the body’s
organs, studies have linked thyroid conditions with other
diseases like kidney [
], liver [
], and heart [
Thyroid disorders disproportionately impact women
], and the rates of thyroid cancer are increasing
globally, with women having higher rates of thyroid cancer
than men, and older women having higher rates than
younger women [
]. We know of only one study that
evaluated PBDE-associated health effects in a
representative U.S. population sample (NHANES) and those
researchers found associations with diabetes and
metabolic syndrome [
], but did not evaluate thyroid disease
as an outcome. Further, we know of no research related to
the potential sensitivity of menopausal women to thyroid
disease based on PBDE concentration, despite the
welldescribed role of estrogen on thyroid function [
the ability of PBDEs to exert estrogenic effects [
objective of our research was to explore the relationship
between PBDE exposures in women and thyroid disease
using nationally-representative (U.S.) data from the
At the time of publication, NHANES reported PBDE
concentrations in serum for individuals (i.e., not pooled) for
only one NHANES cycle: 2003–2004. We analyzed the
data for the four PBDE congeners reported by NHANES
(BDEs 47, 99, 100 and 153), all primarily associated with
the PentaBDE commercial product; information on BDE
209, the primary congener of the DecaBDE commercial
product, has yet to be reported in any NHANES cycle.
Other researchers thoroughly describe the NHANES
analytical methods for serum PBDE measurements and
summary statistics for the population-weighted concentrations
]. We created exposure categories based on quartiles of
lipid-adjusted, sex-specific serum concentrations for each
congener as reported by Sjodin et al. [
]. In addition, we
generated a variable for total sum of lipid-adjusted PBDE
concentrations, which combined the concentrations from
the four congeners (ΣBDE).
Outcome variable—thyroid disease
Thyroid hormone measurements are available in NHANES
but did not overlap completely with the participants for
whom PBDE serum measurements were also available. The
NHANES questionnaire administered to all participants
in NHANES 2003–2004 included two questions related to
thyroid disease: MCQ160m “Has a doctor or other health
professional ever told (you/SP) that (you/s/he) . . . had a
thyroid problem?” and, MCQ170m “(Do you/Does SP)
still . . . have a thyroid problem?”. Responses included: yes,
no, don’t know or missing. For our analyses, if a subject
responded “don’t know” then the data were considered
missing. We used a combination of the thyroid questions
to develop an outcome variable ‘current thyroid problem’.
We defined having a current thyroid problem as an
affirmative answer to ever having a thyroid problem and
still have a thyroid problem. The sample size for
participants with both PBDE measurements and thyroid disease
status available are as follows: BDE 47, n = 1396; BDE 99,
n = 1378; BDE 100, n = 1413; BDE 153, n = 1413.
Thyroid disease prevalence
To calculate the survey-weighted prevalence of thyroid
problems among the NHANES population, we generated
weighted proportions by gender and post-menopause for
questions MCQ160m (ever) and MCQ170m (current)
according to the NHANES descriptive statistical
We performed statistical analyses using STATA
statistical software package, version 13.0 (StatCorp, College
Station, TX). To estimate odds ratios and 95 %
confidence intervals for development of disease accounting
for the clustered sampling design in NHANES Control
and Prevention (CDC), we used multivariate logistic
regression modeling following procedures recommended
by the Centers for Disease Control and Prevention [
We performed logistic regression analyses in this study
using the STATA ‘svy’ commands to account for NHANES
strata and cluster variables, and represent
populationweighted results. To stratify the analysis to women-only,
we assigned men a near zero weight in accordance with
NHANES guidance. To stratify for women who were
postmenopausal, we created a variable based on women
who had not had one menstrual period in the last
12 months (RHQ031) and also indicated the reason for
not having a period was post-menopause/hysterectomy
(RHD042). Similar to the gender stratification, we
assigned near zero weights to all men and women who
were not postmenopausal.
We adjusted multivariate models for several potential
confounders, using a similar methodology from a recent
study examining thyroid effects in the NHANES study
]. Covariates included in the model, with groupings
in parentheses, were: race/ethnicity (Mexican American,
other Hispanic, non-Hispanic White, non-Hispanic
Black, other race (including multi-racial)); age (continuous
variable); body mass index (BMI) (less than 25, 25–30,
>30), education (less than high school, high school, more
than high school), smoking (ever/never smoked more than
100 cigarettes in lifetime); alcohol consumption (never
consume or at least one drink per week); and current
hormone use (taking birth control pills now, now using
Depo-Provera or injectables, taking estrogen only pills
now, taking progestin only pills now, taking
estrogen/progestin now, using estrogen-only patches now, using
estrogen/progestin patch now).
In the primary models, the first and second quartile
exposure groups (Q1 and Q2) were combined to increase
statistical power and match the approach necessitated for
BDE 99 (for BDE 99, the median serum concentration
reported by Sjodin et al. [
] was ‘non-detect’), similar to
the approach used by Melzer et al. [
In the 2003–4 NHANES survey, the prevalence of
women reporting ever being told by a doctor that they
had a thyroid problem was five times higher than the
prevalence reported by men (16 % v. 3 %; p < 0.05). This
was similar to the finding for those reporting a current
thyroid problem (13 % v. 2 %; p < 0.05) (Table 1). In
comparisons of postmenopausal and premenopausal
women, we found that the prevalence of ever having a
thyroid problem and the prevalence of currently having
a thyroid problem was twice as high for postmenopausal
women (ever: 24 % v. 12 %, p < 0.05; current: 18 % v.
10 %, p < 0.10).
In fully-adjusted, survey-weighted logistic regression
models we found that women in the highest quartile of
serum concentrations for BDE 47, 99, 100 and ΣBDE,
had a greater odds of currently having a thyroid
problem, compared to women in the lower quartiles of serum
concentrations (Table 2); statistically significant
associations were observed for BDE 47 (OR: 1.48; 95 % CI:
1.05–2.09), BDE 99 (OR: 1.78; 95 % CI: 1.16–2.75) and
ΣBDE (OR: 1.61; 95 % CI: 1.1–2.4), and marginally
significant for BDE 100 (OR: 1.50; 95 % CI: 0.97–2.31). The
point estimates of the odds ratios for the 3rd quartile
were less than unity, although only statistically significant
for the ΣBDE variable.
For all PBDE congeners except for BDE 153, the odds
ratios for women in the highest exposure category were
higher when the analysis was restricted to
postmenopausal women. For example, for BDE 47, when all
women were included in the analysis, the odds of having
a current thyroid problem was 1.5 compared to 2.1 for
just postmenopausal women. For BDE 99, this difference
was two-fold, with postmenopausal women in the
highest exposure category having 3.6 times the odds of
having a current thyroid problem (95 % CI: 1.1–11.8),
compared to 1.5 times the odds observed for all women
(95 % CI: 0.97–2.3). The analysis for a current thyroid
problem post-menopause showed odds ratios that were
less than unity for the 3rd quartile.
The NHANES dataset did not contain enough men
with current thyroid disease for our models to converge
in a men-only analysis. In an analysis with all men and
women combined, we did not find significant
associations between the exposure categories and current
thyroid disease (Table 1). Similarly, we originally attempted
to explore thyroid cancer specifically, but this NHANES
cycle only had nine participants reporting thyroid cancers,
precluding us from performing regression analysis.
Our study found a positive association between PBDEs
in serum and thyroid disease in U.S. women, a finding
that suggests that effects of PBDEs on thyroid hormones,
documented extensively in toxicological and
epidemiological studies, is leading to significant downstream
impacts. For example, increased PBDE levels in animals,
primarily in mice and rats studies, have been associated
with altered T4 and T3 levels [
] suggesting thyroid
dysregulation in vivo, with several proposed mechanisms
of action [
]. Associations between thyroid hormone
levels and PBDEs have also been observed for animals in
***p < 0.01,**p < 0.05, *p < 0.1
(95 % CI)
the wild, including birds, fish, and polar bears [
humans, there are many studies that describe similar
findings of associations between PBDE concentrations in
serum and thyroid hormone concentrations [
21, 25, 26,
One possible mechanism accounting for the
PBDEinduced reduction in serum T4 is displacement of T4 from
the serum binding protein transthyretin (TTR) or thyroxine
binding globulin (TBG) [
]—similar to what has been
previously observed for polychlorinated biphenyls (PCBs)
]. (Significantly, a study examining the effects of
chemical mixtures observed a potentially synergistic effect on
T4 levels with co-exposures to BDE 47 and PCBs [
T3 and T4 travel in blood bound to plasma proteins; only
0.04 % of T4 and 0.4 % of T3 are unbound (or “free”), and
consequently, available for entry and action in target
]. The tetra-brominated congeners, BDE 47 in
particular, share a similar structure to T4, with both having
the diphenyl ether structure and four halogens (iodine for
T4; bromine for BDE47). A major difference is that T4
has a hydroxyl group on one of the rings, positioned
between the two halogens. However, PBDEs are
hydroxylated in vivo and, when this occurs in the meta position, it
yields 3-OH-BDE47, which also has the hydroxyl group
positioned between two halogens [
Along with epidemiological and toxicological evidence
showing perturbations in thyroid hormone concentrations,
we are now beginning to understand plausible mechanisms
by which this disruption is occurring; the similarity of
structures of exogenous chemicals to endogenous hormones
may be leading to competition for receptor binding sites,
causing inhibition or amplification. For thyroid hormones,
a study by Cao et al. [
] found that hydroxylated PBDEs
bind to transthyretin (TTR) and thyroxine-binding
globulin (TBG) at the same sites as the target hormone, T4.
Hamers et al. measured binding affinities for PBDEs and
metabolites to TTR and reported that the hydroxylated
metabolites bound 160–1600 times more avidly than the
parent compounds [
]. Further, a study by Butt and
] found that hydroxylated PBDEs are potent
inhibitors of thyroid hormone sulfation. Also relevant to
our study that focused on menopausal status, hydroxylated
PBDEs have been shown to compete with estrogen
enzymes. A crystallographic analysis examining the binding
affinity of 3-OH-BDE47 to a hormone enzyme, estrogen
sulfotransferase, demonstrated that the first phenolic group
positions the compound within the enzyme similarly to
how 17βestradiol would situate [
]. Further, the authors
demonstrated that this positioning creates additional
hydrogen bonding via the hydroxyl group, also similar to
17βestradiol, while accommodating the two halogens.
Perhaps the most striking and unique finding in this
study is that the odds of having a current thyroid
problem associated with PBDEs are so much higher in
postmenopausal women. One hypothesis is that this is
related to the change in hormone concentrations in
postmenopausal women and the affinity of PBDEs to
binding sites for both estrogen and thyroid hormones.
Menopause is initiated when the ovaries discontinue
producing two hormones, estrogen and progesterone.
In at least two ways, the strong binding affinity of
OH-PBDEs with estrogen sulfotransferase can interfere
with the change in estrogen levels that occur during
menopause. First, with less estrogen in the system, there
may be increased metabolism of PBDEs by this estrogen
]. Second, the OH-PBDEs may be competing
for these binding sites that are critical for the removal of
circulating estrogen produced by other tissues, leading to
higher than expected levels of circulating estrogen. This
potential interference of the estrogen clearance pathway
in the liver via estrogen sulfotransferase, in and of itself,
would not explain the higher odds of thyroid problems.
However, estrogen (and androgen) can increase the levels
of serum thyroxine binding globulin (TBG), interfering
with one of the three primary proteins responsible for
thyroid hormone transport in serum. In addition to these
potential impacts on thyroid hormone via
estrogenmediated pathways, PBDEs can also have a direct impact
on thyroid hormones through serum binding proteins
outside of the mechanism that involves estrogen; PBDEs
show a strong affinity for both TBG and another serum
binding protein, transthyretin, and therefore can have a
more direct impact on circulating thyroid hormone levels
]. All of this suggests the disruption of thyroid
signaling by PBDEs that may be enhanced by the altered
estrogen levels during menopause.
Results from epidemiologic studies on the effects of
PBDEs on thyroid hormones are consistent with the
toxicological evidence, in that they suggest interference with
thyroid hormone regulation. However, in some
epidemiologic studies, estimates of PBDE exposure are positively
associated with measures of thyroid function, and in
others the opposite pattern is observed. For example, in a
study of 297 infants, Herbstman et al. observed that cord
blood serum PBDE levels were associated with reduced
total and free T4 levels [
]. Conversely, Turyk et al.
(2008) conducted a study of 405 adult male sport fish
consumer and observed a positive trend between free T4
and PBDE serum levels [
]. A more recent study found a
positive association between PBDEs in serum of pregnant
women and serum total and free T4 and T3 [
There are seeming inconsistencies, then, in the
epidemiological literature, with some studies showing
positive associations with PBDEs and thyroid hormones and
others showing negative associations. We note that the
PBDE serum concentrations in many of these cohort
studies are in different ranges of the concentration
distribution found in the U.S. population, with some
representing the low-end of exposure and others on the
high-end (selected studies; Table 3) [
21, 25, 26, 29,
]. Moreover, it seems reasonable to consider the
possibility that adults and fetuses have many differences in
thyroid physiology that could account for at least some of
these differences. However, we hypothesize that a
potential explanation of the differences in findings is due to: 1)
non-monotonic dose responses to PBDEs, and 2) where
on the dose–response range the studies were performed.
Within our study using NHANES data, which represents
the full range of population exposures in the U.S. and
therefore in theory encompasses the ranges found in these
other studies, we also observed that the shape of the
response curve is non-linear and suggests a non-monotonic
dose response curve (NMDRC) may exist (e.g. Q1 + Q2
have higher odds of current thyroid problem relative to
Q3; Q4 also has higher odds of current thyroid problem
relative to Q3). Vandenberg et al. [
] published a seminal
paper evaluating the literature related to endocrine
disrupting chemicals and low-dose and nonmonotonic dose
responses, with significant implications to our current
approach to protecting public health [
]. Vandenberg et al.
state that NMDRCs are, “not the exception, but should be
expected and perhaps even common,” and that it is no
longer acceptable to dismiss NMDRCs based on a lack of
mechanism because there are now several potential
mechanisms to explain these phenomena [
]. These include
cytotoxicity (toxic at high concentrations and biologically
active at low concentrations), cell- and tissue-specific
receptors and co-factors, receptor sensitivity, and receptor
down-regulation and desensitization, among other
proposed mechanisms. In our analysis, individuals in the first
and last quartiles (Q1 + Q2 and Q4) have higher odds of a
thyroid problem, compared to Q3. Results from the other
study of PBDEs using NHANES that focused on diabetes
and metabolic syndrome were also suggestive of a NMDRC
for BDE 99 [
]. It is possible that the existence of a
NMDRC for PBDEs may explain the seeming inconsistency
across studies examining the relationship between PBDEs
and thyroid hormones. The serum concentrations in these
studies generally fall within very different ranges of the full
distribution of serum concentrations observed in NHANES
(Table 3). For example, the central tendency PBDE
concentrations in Zota et al. [
] fall within the Q4 of NHANES,
and they found that PBDEs were associated lower free T4.
In contrast, the central tendency PBDE concentrations in
Abdelouahab et al. [
] fall within Q3 of NHANES, and
they found that PBDEs were associated with the opposite
effect (higher free T4). More research is needed to fully
explore this hypothesis.
A limitation of our study is the inability of this analysis
to determine causality because the data are
crosssectional; thus, we do not have temporality captured in
the data to know if the exposure preceded the outcome.
Also, the standard approach to analysis of serum
concentrations for lipophilic compounds is to adjust the
concentrations based on lipid-content in the serum and report
the results as ‘lipid-adjusted’. This approach, however,
may have a critical limitation. Thyroid hormones affect
lipid metabolism at several points—synthesis, mobilization
and degradation [
]. If a person has thyroid disease not
caused by PBDE exposure, and the disease increases lipid
metabolism leading to lower lipids in the bloodstream,
then adjusting PBDEs by this lower lipid concentration
yields a higher lipid-adjusted PBDE concentration, creating
the appearance of a positive association between thyroid
disease and PBDEs. Therefore, it is possible that women
who self-report current thyroid disease have elevated
lipidadjusted PBDE concentrations in serum as a result of
having thyroid disease. Further, even if serum concentrations
are not adjusted for lipid content, the concentration in
serum is still impacted by lipid content in the bloodstream,
so a simple solution cannot be using serum concentrations
that are not lipid-adjusted (we performed an analysis using
wet-weight concentrations and found similar results as
when we used lipid-normalized concentrations; Additional
file 1: Table S1). Considering these points, it is plausible
then that the relationship of thyroid dysfunction to PBDEs
could be a function of reverse causality, with PBDE
concentrations, lipid-adjusted or not, simply an outcome of
thyroid dysfunction and altered lipid metabolism.
Another potential limitation of this study is the lack
of specificity in the NHANES questionnaire regarding
thyroid problems. NHANES is a nationally representative
health survey (U.S.) that, due to its breadth, only covers
thyroid-related disease with three non-specific questions:
1) Has your doctor ever told you that you have a thyroid
problem, 2) Do you still have a thyroid problem, and
3) Do you have thyroid cancer. Yet, ‘thyroid problem’
and ‘thyroid cancer’ encompass a wide range of specific
illnesses (e.g., hyperthyroidism, hypothyroidism, nodules,
thyroiditis, goiter; papillary thyroid cancer, follicular
thyroid cancer, medullary thyroid cancer), each with their
own potential etiology (e.g., iodine deficiency, Graves’
disease, Hashimoto’s disease, radiation, environmental
chemicals). Despite the lack of specificity in the NHANES
questions on the outcome variables, which would likely
bias the results toward a null finding, we still observed
strong and consistent associations between PBDEs in
serum and thyroid problems. Last, the congeners available
for analysis in NHANES are also from the same
commercial product and are correlated in environmental and body
burden samples [
]. Therefore, we cannot rule out that
one congener is driving the observed associations seen for
Overall, the findings from this analysis of data reported
in NHANES provide additional evidence of the impact
of PBDEs on the thyroid. We also observed a stronger
effect for postmenopausal women. Additional research
is warranted to confirm these findings, particularly
when the next cycle of NHANES data with PBDE serum
concentrations is made available.
We found that women with the highest flame retardant
concentrations in their blood were significantly more
likely to have a thyroid problem, with stronger
associations found for post-menopausal women. Specifically,
women with lipid-adjusted serum concentrations of BDE
47, 99 and 100 in the highest quartile of exposure had
higher odds of having a current thyroid problem
compared to women with lower serum concentrations. These
associations were much stronger in an analysis that was
restricted to postmenopausal women.
This research did not require ethics approval by an
Institutional Review Board (IRB) as the data are de-identified
data from the National Health and Nutrition
Examination Survey (NHANES), a publicly available dataset.
Additional file 1: Table S1. Description of Data: Fully-adjusted,
survey-weighted associations between serum PBDE concentrations
(wet weight) and having a current thyroid problem. (PDF 669 kb)
ΣBDE: Sum of BDEs 47, 99, 100,183; BDE 47: 2,2′4,4′-tetra-bromodiphenyl
ether; BDE 99: 2,2′4,4′5-penta-bromodiphenyl ether; BDE 100:
2,2′,4,4′,6-pentabromodiphenyl ether; BDE 183: 2,2′,3,4,4′,5′,6-hepta-bromodiphenly ether;
BDE 209: deca-bromodiphenyl ether; BMI: body mass index; CDC: Centers for
Disease Control and Prevention; FR: flame retardant; NHANES: National
Health and Nutrition Examination Survey; NMDRC: non-monotonic dose
response curve; NTP: National Toxicology Program; OR: odds ratio;
PBB: polybrominated biphenyl; PBDE: polybrominated diphenyl ether;
PCB: polychlorinated biphenyl; T3: triiodothyronine; T4: Thyroxine;
TBBPA: Tetrabromobisphenol A; TBG: thyroxine-binding globulin;
TSH: thyroid stimulating hormone; TTR: transthyretin.
The authors declare that they have no competing interests.
All authors contributed to the conceptualization of the research, interpretation
of the results and preparation of the manuscript. JA conceived the study,
performed the initial statistical modeling, and drafted the manuscript; SG
performed the final statistical modeling; TZ, LB and JS provided support on the
analysis and interpretation of the results and on manuscript preparation; EM
contributed to the study design and drafting of the manuscript. All authors
read and approved the final manuscript.
This research was supported in part by NIH/NIEHS P30ES000002 and
supported in part by the intramural research project of the National Cancer
Institute/NIH (Birnbaum). This paper does not reflect NIH policy.
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