31 research outputs found
Evaluating the Bioaccessibility of Flame Retardants in House Dust Using an In Vitro Tenax Bead-Assisted Sorptive Physiologically Based Method
Exposure to house
dust is a significant source of exposure to flame
retardant chemicals (FRs), particularly in the US. Given the high
exposure there is a need to understand the bioaccessibility of FRs
from dust. In this study, Tenax beads (TA) encapsulated within a stainless
steel insert were used as an adsorption sink to estimate the dynamic
absorption of a suite of FRs commonly detected in indoor dust samples
(<i>n</i> = 17), and from a few polyurethane foam samples
for comparison. Organophosphate flame retardants (OPFRs) had the highest
estimated bioaccessibility (∼80%) compared to brominated compounds
(e.g., PBDEs), and values generally decreased with increasing Log <i>K</i><sub>ow</sub>, with <30% bioaccessibility measured for
BDE209. These measurements were in very close agreement with reported
PBDE bioavailability measures from an in vivo rat exposure study using
indoor dust. The bioaccessibility of very hydrophobic FRs (Log <i>K</i><sub>ow</sub> > 6) in foam was much less than that in
house
dust, and increasing bioaccessibility was observed with decreasing
particle size. In addition, we examined the stability of more labile
FRs containing ester groups (e.g., OPFRs and 2-ethylhexyl-tetrabromo-benzoate
(EH-TBB)) in a mock-digestive fluid matrix. No significant changes
in the OPFR concentrations were observed in this fluid; however, EH-TBB
was found to readily hydrolyze to tetrabromobenzoic acid (TBBA) in
the intestinal fluid in the presence of lipases. In conclusion, our
study demonstrates that the bioaccessibility and stability of FRs
following ingestion varies by chemical and sample matrix and thus
should be considered in exposure assessments
Inhibition of Thyroid Hormone Sulfotransferase Activity by Brominated Flame Retardants and Halogenated Phenolics
Many halogenated organic contaminants
(HOCs) are considered endocrine
disruptors and affect the hypothalamic–pituitary–thyroid
axis, often by interfering with circulating levels of thyroid hormones
(THs). We investigated one potential mechanism for TH disruption,
inhibition of sulfotransferase activity. One of the primary roles
of TH sulfation is to support the regulation of biologically active
T3 through the formation of inactive THs. We investigated TH sulfotransferase
inhibition by 14 hydroxylated polybrominated diphenyl ethers (OH BDEs),
BDE 47, triclosan, and fluorinated, chlorinated, brominated, and iodinated
analogues of 2,4,6-trihalogenated phenol and bisphenol A (BPA). A
new mass spectrometry-based method was also developed to measure the
formation rates of 3,3′-T2 sulfate (3,3′-T2S). Using
pooled human liver cytosol, we investigated the influence of these
HOCs on the sulfation of 3,3′-T2, a major substrate for TH
sulfation. For the formation of 3,3′-T2S, the Michaelis constant
(<i>K</i><sub>m</sub>) was 1070 ± 120 nM and the <i>V</i><sub>max</sub> was 153 ± 6.6 pmol min<sup>–1</sup> (mg of protein)<sup>−1</sup>. All chemicals investigated
inhibited sulfotransferase activity with the exception of BDE 47.
The 2,4,6-trihalogenated phenols were the most potent inhibitors followed
by the OH BDEs and then halogenated BPAs. The IC<sub>50</sub> values
for the OH BDEs were primarily in the low nanomolar range, which may
be environmentally relevant. <i>In silico</i> molecular
modeling techniques were also used to simulate the binding of OH BDE
to SULT1A1. This study suggests that some HOCs, including antimicrobial
chemicals and metabolites of flame retardants, may interfere with
TH regulation through inhibition of sulfotransferase activity
Effect-Directed Analysis of Human Peroxisome Proliferator-Activated Nuclear Receptors (PPARγ1) Ligands in Indoor Dust
Agonism
of human peroxisome proliferator-activated nuclear receptor
gamma (PPARγ1) was recently observed in 15 of 25 samples of
indoor dust extracts at environmentally relevant exposure levels.
In this study, an effect-directed analysis approach was used to identify
the primary contributors of PPARγ1 activity in the dust extracts.
Three dust extracts showing significant PPARγ1 activity were
fractionated with normal phase high-performance liquid chromatography
(NP-HPLC) and each fraction was tested for PPARγ1 activity.
Three dust extracts showed a similar PPARγ1 activity distribution
in the NP-HPLC fractions. In most active fractions, fatty acids (FAs),
including oleic acid, stearic acid, palmitic acid and myristic acid,
were the primary chemicals identified using gas-chromatography mass
spectrometry (GC-MS). Chemical measurements of the FAs in house dust
extracts revealed a positive and significant correlation with the
observed PPARγ1 activity. To test the role of FAs in the activity,
a mixture of four FAs was prepared in the ratios measured in the dust
samples and tested for activity. The activity of this mixture was
30–50% of the activity observed in the dust extracts, suggesting
they were contributing to the observed activity, but also suggesting
additional unknown compounds are likely still present in the dust
extracts. To tentatively identify sources of FAs in the dust samples,
FAs were quantified in human/animal hair, dead skin cells, and cooking
oil. FAs were abundant in all samples and our data indicate that all
of these may be sources to indoor dust
Disruption of Type 2 Iodothyronine Deiodinase Activity in Cultured Human Glial Cells by Polybrominated Diphenyl Ethers
Polybrominated
diphenyl ether (PBDE) flame retardants are endocrine
disruptors and suspected neurodevelopmental toxicants. While the direct
mechanisms of neurodevelopmental toxicity have not been fully elucidated,
it is conceivable that alterations in thyroid hormone levels in the
developing brain may contribute to these effects. Cells within the
brain locally convert thyroxine (T<sub>4</sub>) to the biologically
active triiodothyronine (T<sub>3</sub>) through the action of the
selenodeiodinase type 2 iodothyronine deiodinase (DIO2). Previous
studies have demonstrated that PBDEs can alter hepatic deiodinase
activity both in vitro and in vivo; however, the effects of PBDEs
on the deiodinase isoforms expressed in the brain are not well understood.
Here, we studied the effects of several individual PBDEs and hydroxylated
metabolites (OH-BDEs) on DIO2 activity in astrocytes, a specialized
glial cell responsible for production of more than 50% of the T<sub>3</sub> required by the brain. Primary human astrocytes and H4 glioma
cells were exposed to individual PBDEs or OH-BDEs at concentrations
up to 5 μM. BDE-99 decreased DIO2 activity by 50% in primary
astrocyte cells and by up to 80% in the H4 cells at doses of ≥500
nM. 3-OH-BDE-47, 6-OH-BDE-47, and 5′-OH-BDE-99 also decreased
DIO2 activity in cultured
H4 glioma cells by 45–80% at doses of approximately 1–5
μM. Multiple mechanisms appear to contribute to the decreased
DIO2 activity, including weakened expression of <i>DIO2</i> mRNA, competitive inhibition of DIO2, and enhanced post-translational
degradation of DIO2. We conclude that decreases in DIO2 activity caused
by exposure to PBDEs may play a role in the neurodevelopmental deficits
caused by these toxicants
Associations of birth outcomes with maternal polybrominated diphenyl ethers and thyroid hormones during pregnancy
Background - Previous research has linked polybrominated diphenyl ether (PBDE) exposure to poor birth outcomes and altered thyroid hormone levels. Objectives - We examined whether maternal PBDE serum levels were associated with infant birth weight (g), head circumference (cm), birth length (cm), and birth weight percentile for gestational age. We explored the potential for a mediating role of thyroid hormone levels. Methods - During 2008–2010, we recruited 140 pregnant women in their third trimester as part of a larger clinical obstetrics study known as Healthy Pregnancy, Healthy Baby. Blood samples were collected during a routine prenatal clinic visit. Serum was analyzed for PBDEs, phenolic metabolites, and thyroid hormones. Birth outcome information was abstracted from medical records. Results - In unadjusted models, a two-fold increase in maternal BDE 153 was associated with an average decrease in head circumference of 0.32 cm (95% CI: − 0.53, − 0.12); however, this association was attenuated after control for maternal risk factors. BDE 47 and 99 were similarly negatively associated but with 95% confidence intervals crossing the null. Associations were unchanged in the presence of thyroid hormones. Conclusions - Our data suggest a potential deleterious association between maternal PBDE levels and infant head circumference; however, confirmatory studies are needed in larger sample sizes. A mediating role of thyroid hormones was not apparent
Characterization and Adaptation of Anaerobic Sludge Microbial Communities Exposed to Tetrabromobisphenol A
<div><p>The increasing occurrence of tetrabromobisphenol A (TBBPA) in the environment is raising questions about its potential ecological and human health impacts. TBBPA is microbially transformed under anaerobic conditions to bisphenol A (BPA). However, little is known about which taxa degrade TBBPA and the adaptation of microbial communities exposed to TBBPA. The objectives of this study were to characterize the effect of TBBPA on microbial community structure during the start-up phase of a bench-scale anaerobic sludge reactor, and identify taxa that may be associated with TBBPA degradation. TBBPA degradation was monitored using LC/MS-MS, and the microbial community was characterized using Ion Torrent sequencing and qPCR. TBBPA was nearly completely transformed to BPA <i>via</i> reductive debromination in 55 days. Anaerobic reactor performance was not negatively affected by the presence of TBBPA and the bulk of the microbial community did not experience significant shifts. Several taxa showed a positive response to TBBPA, suggesting they may be associated with TBBPA degradation. Some of these taxa had been previously identified as dehalogenating bacteria including <i>Dehalococcoides</i>, <i>Desulfovibrio</i>, <i>Propionibacterium</i>, and <i>Methylosinus</i> species, but most had not previously been identified as having dehalogenating capacities. This study is the first to provide in-depth information on the microbial dynamics of anaerobic microbial communities exposed to TBBPA.</p></div
Dynamics of methanogenic, archaeal, and bacterial populations.
<p>Quantification of the <i>mcrA</i> gene, archaeal 16S rDNA, and bacterial 16S rDNA as measured by qPCR. Efficiency and R<sup>2</sup> calculated from the standard curves were 89.7% and 0.911, 86.7% and 0.982, and 88.3% and 0.998, for the <i>mcrA</i>, archaeal, and bacterial 16S rDNA assays, respectively. Error bars represent the standard deviation from the mean. Different letters above bars indicate significant differences, according to a t-test (p ≤0.05), between days. If a bracket and an asterisk are present between two bars, it indicates that the two corresponding samples are significantly different, according to a t-test (p ≤0.05), performed within each day separately.</p
Weighted UniFrac matrix-based Principal Coordinate Analysis (PCoA) and Analysis of Similarity (ANOSIM) results.
<p>The percentage of variation explained for the x and y-axis are indicated on the graph. The table indicates the results of the ANOSIM analyses performed on the weighted UniFrac matrix generated. The null hypothesis (H<sub>0</sub>) states that there is no difference between groups in terms of community composition. H<sub>0</sub> is rejected if p>0.05. An R-value close to 1 indicates an important differences between the groups tested, while an R-value close to 0 indicates a small difference between the groups tested in terms of community composition.</p
TBBPA degradation and formation of BPA.
<p>Concentration of TBBPA, BPA, and degradation by-products (i.e., 3,3',5-tribromobisphenol, 3,3'-dibromobisphenol and 3-bromobisphenol A) in metabolic (a) and co-metabolic (b) reactors overtime. Error bars represent standard deviation from the mean. TBBPA reductive debromination pathway is shown above the graphs.</p
List of the 32 OTUs extracted from our Ion Torrent dataset that were more abundant in TBBPA-spiked than in the control reactors.
<p>List of the 32 OTUs extracted from our Ion Torrent dataset that were more abundant in TBBPA-spiked than in the control reactors.</p