70 research outputs found
Human dietary intake and hazard characterization for residues of neonicotinoides and organophosphorus pesticides in Egyptian honey
<p>In two recently published reports, hazards posed by dietary exposure to organophosphate and neonicotinoid plant protection products on the European honey bee (<i>Apis mellifera</i> L.) in Egypt were investigated. Using concentrations reported in those studies, an assessment of hazards posed by these two classes of insecticides to humans due to consumption of Egyptian honey from the Nile Delta during both spring and summer was performed. Twenty-eight compounds including metabolites were assessed for exposure of adult Egyptians based on the best- and worst-case scenarios. Even for the worst-case scenario, exposure to these two classes of pesticides in honey was 15-fold less than hazard index value of 1.0 for adverse effects on humans. Based upon this analysis, people exposed to these insecticides through consumption of honey products would be unlikely to exhibit adverse health outcomes.</p
A Cross-species Quantitative Adverse Outcome Pathway for Activation of the Aryl Hydrocarbon Receptor Leading to Early Life Stage Mortality in Birds and Fishes
Dioxin-like compounds (DLCs) elicit
adverse effects through activation
of the aryl hydrocarbon receptor (AHR). Prior investigations demonstrated
that sensitivity to activation of AHR1 in an in vitro AHR transactivation
assay is predictive of early life stage mortality among birds. The
present study investigated the link between sensitivity to activation
of AHR1s and AHR2s and early life stage mortality among fishes. A
significant, linear relationship was demonstrated between sensitivity
to activation of AHR2 and early life stage mortality among nine fishes,
while no relationship was found for AHR1. The slope and <i>y</i>-intercept for the linear relationship between sensitivity to activation
of AHR1 and early life stage mortality in birds was not statistically
different from the same relationship for AHR2 in fishes. Data for
fishes and birds across DLCs were expanded into four significant,
linear regression models describing the relationship between sensitivity
to activation of AHR and the dose to cause early life stage mortality
of 0%, 10%, 50%, or 100%. These four relationships were combined to
form a quantitative adverse outcome pathway which can predict dose–response
curves of early life stage mortality for DLCs to any bird or fish
from species- and chemical-specific responses in an in vitro AHR transactivation
assay
A Cross-species Quantitative Adverse Outcome Pathway for Activation of the Aryl Hydrocarbon Receptor Leading to Early Life Stage Mortality in Birds and Fishes
Dioxin-like compounds (DLCs) elicit
adverse effects through activation
of the aryl hydrocarbon receptor (AHR). Prior investigations demonstrated
that sensitivity to activation of AHR1 in an in vitro AHR transactivation
assay is predictive of early life stage mortality among birds. The
present study investigated the link between sensitivity to activation
of AHR1s and AHR2s and early life stage mortality among fishes. A
significant, linear relationship was demonstrated between sensitivity
to activation of AHR2 and early life stage mortality among nine fishes,
while no relationship was found for AHR1. The slope and <i>y</i>-intercept for the linear relationship between sensitivity to activation
of AHR1 and early life stage mortality in birds was not statistically
different from the same relationship for AHR2 in fishes. Data for
fishes and birds across DLCs were expanded into four significant,
linear regression models describing the relationship between sensitivity
to activation of AHR and the dose to cause early life stage mortality
of 0%, 10%, 50%, or 100%. These four relationships were combined to
form a quantitative adverse outcome pathway which can predict dose–response
curves of early life stage mortality for DLCs to any bird or fish
from species- and chemical-specific responses in an in vitro AHR transactivation
assay
Effects of Exposure to 17α-Ethynylestradiol during Sexual Differentiation on the Transcriptome of the African Clawed Frog (<i>Xenopus laevis</i>)
Exposure to estrogens during the
period of sexual differentiation
is known to adversely affect the development of testes in African
clawed frogs (<i>Xenopus</i> laevis), but little is known
about molecular changes that coincide with the development of altered
phenotypes. Therefore, the transcriptome-level effects of exposure
to 17α-ethynylestradiol (EE2) during sexual differentiation
of <i>X. laevis</i> were evaluated by use of <i>Illumina</i> sequencing coupled with RNA-Seq expression analysis. Overall, a
number of processes were affected by 17α-ethynylestradiol, including
steroid biosynthesis, thyroid hormone signaling and metabolism, testicular
development, and spermatogenesis. Some of the altered pathways, such
as thyroid hormone signaling and testicular development, could be
linked with biological effects on metamorphosis and gonadal phenotypes,
respectively, that were observed in frogs that were exposed to 17α-ethynylestradiol
throughout metamorphosis and the early postmetamorphic period. Thus,
early changes at the transcriptome-level were predictive of pathologies
that did not manifest until later in development. To validate the
quantitative capacity of RNA-Seq, a subset of transcripts identified
to have altered abundances in individuals exposed to 17α-ethynylestradiol
was also evaluated by use of quantitative polymerase chain reaction
(qPCR). While small sample sizes (<i>n</i> = 3) limited
the ability to draw conclusions pertaining to differences in qPCR-derived
abundances of transcripts between control and exposed tadpoles, there
was a significant relationship (<i>r</i><sup>2</sup> = 0.78)
between fold-changes for RNA-Seq and qPCR
A Reagent-Free Screening Assay for Evaluation of the Effects of Chemicals on the Proliferation and Morphology of HeLa-GFP Cells
A reagent-free screening
assay using HeLa cells with green fluorescent
protein expressed in the cytoplasm was developed to describe adherence
and proliferation of cells after seeding and to evaluate the dose-
and time-dependent effects of three classes of chemicals, including
metals (CdCl<sub>2</sub>, MeHg, HgCl<sub>2</sub>, and NiCl<sub>2</sub>), flame retardants [trisÂ(1,3-dichloro-2-propyl) phosphate, heptadecafluoro-1-octanesulfonic
acid, tetrabromobisphenol A, and trisÂ(2-chloroethyl) phosphate], and
phenolic fungicides (2,4,6-trichlorophenol, 4-<i>tert</i>-butylphenol, 3-bromophenol, and 2,4-dibromophenol), on the proliferation
and morphology of cells. A seeding density of 5000 cells/well was
determined to be optimal, and the most suitable duration of xenobiotic
exposure was 120 h beginning 58 h postseeding. Dose- and time-dependent
alterations in total fluorescence in the fluorescent field and number
of cells, area per cell, and cellular roundness in the bright field
were identified after exposure to each of the target chemicals. Results
were comparable to those of the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium
bromide assay or other end points published in the literature for
the same chemicals
Responses of the Proteome and Metabolome in Livers of Zebrafish Exposed Chronically to Environmentally Relevant Concentrations of Microcystin-LR
In
this study, for the first time, changes in expressions of proteins
and profiles of metabolites in liver of the small, freshwater fish Danio rerio (zebrafish) were investigated after
long-term exposure to environmentally relevant concentrations of microcystin-LR
(MC-LR). Male zebrafish were exposed via water to 1 or 10 ÎĽg
MC-LR/L for 90 days, and iTRAQ-based proteomics and <sup>1</sup>H
NMR-based metabolomics were employed. Histopathological observations
showed that MC-LR caused damage to liver, and the effects were more
pronounced in fish exposed to 10 ÎĽg MC-LR/L. Metabolomic analysis
also showed alterations of hepatic function, which included changes
in a number of metabolic pathways, including small molecules involved
in energy, glucose, lipids, and amino acids metabolism. Concentrations
of lactate were significantly greater in individuals exposed to MC-LR
than in unexposed controls. This indicated a shift toward anaerobic
metabolism, which was confirmed by impaired respiration in mitochondria.
Proteomics revealed that MC-LR significantly influenced multiple proteins,
including those involved in folding of proteins and metabolism. Endoplasmic
reticulum stress contributed to disturbance of metabolism of lipids
in liver of zebrafish exposed to MC-LR. Identification of proteins
and metabolites in liver of zebrafish responsive to MC-LR provides
insights into mechanisms of chronic toxicity of MCs
Identification of Thyroid Hormone Disruptors among HO-PBDEs: <i>In Vitro</i> Investigations and Coregulator Involved Simulations
Some hydroxylated
polybrominated diphenyl ethers (HO-PBDEs), that
have been widely detected in the environment and tissues of humans
and wildlife, bind to thyroid hormone (TH) receptor (TR) and can disrupt
functioning of systems modulated by the TR. However, mechanisms of
TH disrupting effects are still equivocal. Here, disruption of functions
of TH modulated pathways by HO-PBDEs was evaluated by assays of competitive
binding, coactivator recruitment, and proliferation of GH3 cells. <i>In silico</i> simulations considering effects of coregulators
were carried out to investigate molecular mechanisms and to predict
potencies for disrupting functions of the TH. Some HO-PBDEs were able
to bind to TR with moderate affinities but were not agonists. In GH3
proliferation assays, 13 out of 16 HO-PBDEs were antagonists for the
TH. <i>In silico</i> simulations of molecular dynamics revealed
that coregulators were essential for identification of TH disruptors.
Among HO-PBDEs, binding of passive antagonists induced repositioning
of H12, blocking AF-2 (transactivation function 2) and preventing
recruitment of the coactivator. Binding of active antagonists exposed
the coregulator binding site, which tended to bind to the corepressor
rather than the coactivator. By considering both passive and active
antagonisms, anti-TH potencies of HO-PBDEs could be predicted from
free energy of binding
Mechanisms of Toxicity of Hydroxylated Polybrominated Diphenyl Ethers (HO-PBDEs) Determined by Toxicogenomic Analysis with a Live Cell Array Coupled with Mutagenesis in Escherichia coli
Results
of previous studies have indicated that 6-HO-BDE-47, the
addition of the hydroxyl (HO) group to the backbone of BDE-47, significantly
increased the toxicity of the chemical compared to its postulated
precursor analogues, BDE-47 and 6-MeO-BDE-47. However, whether such
a result is conserved across polybrominated diphenyl ether (PBDE)
congeners was unknown. Here, cytotoxicity of 32 PBDE analogues (17
HO-PBDEs and 15 MeO-PBDEs) was further tested and the underlying molecular
mechanism was investigated. A total of 14 of the 17 HO-PBDEs inhibited
growth of Escherichia coli during 4
or 24 h durations of exposure, but none of the MeO-PBDEs was cytotoxic
at the concentrations tested. 6-HO-BDE-47 and 2-HO-BDE-28 were most
potent with 4 h median effect concentrations (EC<sub>50</sub>) of
12.13 and 6.25 mg/L, respectively, which trended to be lesser with
a longer exposure time (24 h). Expression of 30 modulated and validated
genes by 6-HO-BDE-47 in a previous study was also observed after exposure
to other HO-PBDE analogues. For instance, <i>uhpT</i> was
upregulated by 13 HO-PBDEs, and three rRNA operons (<i>rrnA</i>, <i>rrnB</i>, and <i>rrnC</i>) were downregulated
by 8 HO-PBDEs. These unanimous responses suggested a potential common
molecular signaling modulated by HO-PBDEs. To explore new information
on mechanisms of action, this work was extended by testing the increased
susceptibility of 182 mutations of transcriptional factors (TFs) and
22 mutations as genes modulated by 6-HO-BDE-47 after exposure to 6-HO-BDE-47
at the 4 h IC<sub>50</sub> concentration. Although a unanimous upregulation
of <i>uhpT</i> was observed after exposure to HO-PBDEs,
no significant shift in sensitivity was observed in <i>uhpT</i>-defective mutants. The 54 genes, selected by cut-offs of 0.35 and
0.65, were determined to be responsible for “organic acid/oxoacid/carboxylic
acid metabolic process” pathways, which supported a previous
finding
Isomer-Specific Accumulation of Perfluorooctanesulfonate from (<i>N</i>‑Ethyl perfluorooctanesulfonamido)ethanol-based Phosphate Diester in Japanese Medaka (Oryzias latipes)
While
(<i>N</i>-ethyl perfluorooctanesulfonamido)Âethanol
(FOSE) -based phosphate diester (diSPAP) has been proposed as a candidate
precursor of perfluorooctanesulfonate (PFOS), its potential biotransformation
to PFOS has not been verified. Metabolism of diSPAP was investigated
in Japanese medaka (Oryzias latipes) after exposure in water for 10 days, followed by 10 days of depuration.
Branched isomers of diSPAP (B-diSPAP) were preferentially enriched
in medaka exposed to diSPAP, with the proportion of branched isomers
(BF) ranging from 0.56 to 0.80, which was significantly greater than
that in the water to which the medaka were exposed (0.36) (<i>p</i> < 0.001). This enrichment was due primarily to preferential
uptake of B-diSPAP. PFOS together with perfluorooctanesulfonamide
(PFOSA), <i>N</i>-ethyl perfluorooctanesulfonamide (NEtFOSA),
2-(perfluorooctanesulfonamido)Âacetic acid (FOSAA), NEtFOSAA, FOSE,
and NEtFOSE were detected in medaka exposed to diSPAP, which indicated
the potential for biotransformation of diSPAP to PFOS via multiple
intermediates. Due to preferential metabolism of branched isomers,
FOSAA and PFOSA exhibited greater BF values (>0.5) than those of
NEtFOSA,
NEtFOSAA, and NEtFOSE (<0.2). Such preferential metabolism of branched
isomers along the primary pathway of metabolism and preferential accumulation
of B-diSPAP led to enrichment of branched PFOS (B-PFOS) in medaka.
Enrichment of B-PFOS was greater for 3-, 4-, and 5-perfluoromethyl
PFOS (P<sub>3</sub>MPFOS, P<sub>4</sub>MPFOS, and P<sub>5</sub>MPFOS),
for which values of BF were 0.58 ± 0.07, 0.62 ± 0.06, and
0.61 ± 0.05 (day 6), respectively; these values are 5.8-, 7.8-,
and 6.4-fold greater than those of technical PFOS. This work provides
evidence on the isomer-specific accumulation of PFOS from diSPAP and
will be helpful to track indirect sources of PFOS in the future
Occurrences and Fates of Hydroxylated Polybrominated Diphenyl Ethers in Marine Sediments in Relation to Trophodynamics
While occurrences and origins of hydroxylated (OH-) polybrominated
diphenyl ethers (PBDEs) in organisms have been reported, the fates
of these compounds in abiotic matrixes and related trophodynamics
are unclear. The present study measured concentrations of nine OH-PBDEs,
twelve methoxylated (MeO-) PBDEs, and eleven PBDEs in marine sediments
and explored the trophodynamics of OH-PBDEs in five invertebrates,
eight fish, and two species of birds from Liaodong Bay, north China.
While concentrations of PBDEs were less than the limit of quantification
in sediments, concentrations of ÎŁOH-PBDEs and ÎŁMeO-PBDEs
were 3.2–116 pg/g dry weight (dw) and 3.8–56 pg/g dw,
respectively. When the detected compounds were incubated in native
marine sediments the interconversion between 6-OH-BDE47 and 6-MeO-BDE47
was observed. This result is consistent with the similar spatial distributions
and significant correlation between the concentrations of these naturally
occurring compounds. 6-OH-BDE47 and 2′-OH-BDE68 were detected
as the two major congeners in organisms collected from Liaodong Bay,
and concentrations were 0.24 ± 0.005 ng/g lw (lipid weight) and
0.088 ± 0.006 ng/g lw, respectively. Biota-sediment accumulation
factors (BSAFs) for invertebrates of 6-OH-BDE47 and 2′-OH-BDE68
were 0.017–0.96 and 0.19–1.5 (except for short-necked
clam: 6.3), respectively. Lipid-normalized concentrations of 6-OH-BDE47
and 2′-OH-BDE68 decreased significantly with trophic level
with TMFs of 0.21 and 0.15, respectively. The fates of OH-PBDEs in
sediment together with their trophodynamics in marine food webs suggested
that OH-PBDEs are partitioned into sediment and undergo biodilution
in the marine food web
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