Chemical Research in Toxicology,
Год журнала:
2024,
Номер
37(9), С. 1549 - 1561
Опубликована: Авг. 29, 2024
Emerging
environmental
contaminants,
organophosphate
flame
retardants
(OPFRs),
pose
significant
threats
to
ecosystems
and
human
health.
Despite
numerous
studies
reporting
the
toxic
effects
of
OPFRs,
research
on
their
epigenetic
alterations
remains
limited.
In
this
study,
we
investigated
exposure
2-ethylhexyl
diphenyl
phosphate
(EHDPP),
tricresyl
(TMPP),
triphenyl
(TPHP)
DNA
methylation
patterns
during
zebrafish
embryonic
development.
We
assessed
general
toxicity
morphological
changes,
measured
global
hydroxymethylation
levels,
evaluated
methyltransferase
(DNMT)
enzyme
activity,
as
well
mRNA
expression
DNMTs
ten-eleven
translocation
(TET)
methylcytosine
dioxygenase
genes.
Additionally,
analyzed
genome-wide
in
larvae
using
reduced-representation
bisulfite
sequencing.
Our
assessment
revealed
no
toxicity,
but
a
statistically
yet
subtle
decrease
body
length
following
TMPP
EHDPP,
along
with
reduction
head
height
after
TPHP
exposure,
was
observed.
Eye
diameter
width
were
unaffected
by
any
OPFRs.
There
changes
levels
group,
showed
clear
effect
DNMT
expression.
However,
EHDPP
significantly
decreased
only
DNMT1
expression,
while
reduced
several
orthologues
TETs
larvae,
leading
aberrant
methylation.
Differential
occurred
primarily
introns
(43%)
intergenic
regions
(37%),
9%
10%
occurring
exons
promoter
regions,
respectively.
Pathway
enrichment
analysis
differentially
methylated
region-associated
genes
indicated
that
enhanced
biological
molecular
functions
corresponding
metabolism
neurological
KEGG
further
TPHP-mediated
potential
signaling
pathways
including
TGFβ,
cytokine,
insulin
signaling.
This
study
identifies
specific
brings
novel
insights
into
mode
action
TPHP.
The Science of The Total Environment,
Год журнала:
2023,
Номер
897, С. 165272 - 165272
Опубликована: Июль 3, 2023
Flame
retardants
(FRs)
are
chemical
substances
used
to
inhibit
the
spread
of
fire
in
numerous
industrial
applications,
and
their
abundance
modern
manufactured
products
indoor
outdoor
environment
leads
extensive
direct
food
chain
exposure
humans.
Although
once
considered
relatively
non-toxic,
FRs
demonstrated
by
recent
literature
have
disruptive
effects
on
many
biological
processes,
including
signaling
pathways,
genome
stability,
reproduction,
immune
system
function.
This
review
provides
a
summary
research
investigating
impact
major
groups
FRs,
halogenated
organophosphorus
animals
humans
vitro
and/or
vivo.
We
put
focus
those
studies
that
explained
or
referenced
modes
FR
action
at
level
cells,
tissues
organs.
Since
highly
hydrophobic
chemicals,
biophysical
biochemical
usually
involve
lipophilic
interactions,
e.g.
with
membranes
elements
pathways.
present
selected
toxicological
information
about
these
molecular
actions
show
how
they
can
lead
damaging
membrane
integrity,
DNA
compromising
its
repair,
changing
gene
expression,
cell
cycle
as
well
accelerating
death.
Moreover,
we
indicate
this
translates
deleterious
bioactivity
physiological
level,
disruption
hormonal
action,
dysregulation
metabolism,
adverse
male
female
reproduction
alteration
normal
pattern
immunity.
Concentrating
subjects,
make
clear
both
advances
knowledge
years
remaining
gaps
our
understanding,
especially
mechanistic
level.
Ecotoxicology and Environmental Safety,
Год журнала:
2024,
Номер
280, С. 116524 - 116524
Опубликована: Июнь 5, 2024
Organophosphate
esters
(OPEs)
and
Per-
polyfluoroalkyl
substances
(PFAS)
are
ubiquitous
environmental
contaminants
with
common
exposure
sources,
leading
to
their
widespread
presence
in
human
body.
However,
evidence
on
co-exposure
OPEs
PFAS
its
impact
cardiovascular-kidney-liver-metabolic
biomarkers
remains
limited.
Cell Biology and Toxicology,
Год журнала:
2024,
Номер
40(1)
Опубликована: Май 21, 2024
Fumonisin
B1
(FB1),
a
water-soluble
mycotoxin
released
by
Fusarium
moniliforme
Sheld,
is
widely
present
in
corn
and
its
derivative
products,
seriously
endangers
human
life
health.
Recent
studies
have
reported
that
FB1
can
lead
to
pyroptosis,
however,
the
mechanisms
which
FB1-induced
pyroptosis
remain
indistinct.
In
study,
we
aim
investigate
of
intestinal
porcine
epithelial
cells
(IPEC-J2)
relationship
between
endoplasmic
reticulum
stress
(ERS)
pyroptosis.
Our
experimental
results
showed
protein
indicators
IPEC-J2
were
significantly
increased
after
exposure
FB1.
The
ERS
markers,
including
glucose-regulated
Protein
78
(GRP78),
PKR-like
ER
kinase
(PERK),
preprotein
translocation
factor
(Sec62)
also
increased.
Using
small
interfering
RNA
silencing
PERK
or
Sec62,
demonstrated
upregulation
Sec62
activates
pathway,
activation
signaling
pathway
upstream
After
using
inhibitor
4-PBA
reduced
FB1-triggered
injury
Sec62-PERK
pathway.
conclusion,
found
induced
upregulating
activate
mild
alleviates
damage.
It
all
boils
down
one
fact,
study
provides
new
perspective
for
further,
improving
toxicological
mechanism
Toxicology Mechanisms and Methods,
Год журнала:
2024,
Номер
unknown, С. 1 - 11
Опубликована: Июль 25, 2024
From
the
past
to
present,
many
chemicals
have
been
used
for
purpose
of
flame
retardant.
Due
PBDEs'
(Polybrominated
diphenyl
ether)
lipophilic
and
accumulative
properties,
some
them
are
banned
from
market.
As
an
alternative
these
chemicals,
OPFRs
(organophosphorus
retardants)
started
be
as
retardants.
In
this
article,
acute
toxicity
profiles,
mutagenicity,
carcinogenicity,
blood-brain
barrier
permeability,
ecotoxicity
nutritional
also
AHR,
ER
affinity
MMP,
aromatase
affinity,
CYP2C9,
CYP3A4
interaction
16
different
compounds
were
investigated
using
a
computational
toxicology
method;
ProTox-
3.0.
According
our
results,
eight
found
active
in
terms
carcinogenic
effect,
whereas
two
mutagenicity.
On
other
hand,
all
blood-barrier
permeability.
Fourteen
four
ecotoxic
toxic
potency,
respectively.
Eight
determined
AhR,
Estrogen
Receptor
alpha.
mitochondrial
membrane
potency.
Lastly,
three
enzymes.
CYP
potencies,
both
CYP2C9
CYP3A4.
This
research
provided
novel
insights
into
potential
effects
OPFRs.
However,
further
studies
needed
evaluate
their
toxicity.
Moreover,
findings
lay
groundwork
Environmental Science & Technology,
Год журнала:
2024,
Номер
58(35), С. 15486 - 15496
Опубликована: Авг. 21, 2024
Aryl
phosphorus
flame
retardants
(aryl-PFRs),
such
as
triphenyl
phosphate
(TPHP)
and
diphenyl
(DPHP),
are
widely
used
worldwide.
Understanding
the
fates
of
aryl-PFRs
Environmental Science & Technology,
Год журнала:
2024,
Номер
58(42), С. 18631 - 18641
Опубликована: Окт. 9, 2024
Cresyl
diphenyl
phosphate
(CDP),
a
novel
organophosphate
ester
(OPE),
has
been
detected
in
various
environmental
and
human
samples.
However,
there
is
very
limited
knowledge
regarding
its
toxicity,
mechanisms
of
action,
potential
health
risks.
Using
new
alternative
methods
(NAMs),
across
the
molecular
interactions,
signaling
pathways,
cell
functions,
animal
effects,
population
risks,
we
investigated
adipogenic
effects
associated
risks
CDP
legacy
OPE
triphenyl
(TPHP)
by
acting
on
peroxisome
proliferator-activated
receptor
gamma
(PPARγ).
Among
19
screened
OPEs,
bound
to
PPARγ
with
highest
binding
potency,
followed
TPHP.
activated
through
fitting
into
pocket
strong
hydrophobicity
hydrogen
bond
interactions;
exhibited
higher
potency
compared
In
3T3-L1
cells,
enhanced
PPARγ-mediated
adipogenesis
activity,
exhibiting
greater
than
The
intracellular
concentration
receptor-bound
concentrations
(RBC)
were
also
those
TPHP
both
HEK293
cells
cells.
mice,
exposure
pathway,
leading
an
increased
white
adipose
tissue
weight
gain.
Overall,
could
bind
activate
PPARγ,
thereby
promoting
preadipocyte
differentiation
development
tissue.
Its
obesogenic
should
be
high
concern.
Environmental Toxicology,
Год журнала:
2023,
Номер
38(7), С. 1484 - 1493
Опубликована: Март 17, 2023
Abstract
Triphenyl
phosphate
(TPHP)
is
one
of
the
most
widely
used
organic
phosphorus
flame
retardants
and
ubiquitous
in
environment.
Studies
have
been
reported
that
TPHP
may
lead
to
obesity,
neurotoxicity
reproductive
toxicity,
but
its
impact
on
immune
system
almost
blank.
The
present
study
was
aimed
investigate
potential
immunotoxicity
macrophages
underlying
mechanism.
results
demonstrated
for
first
time
(12.5,
25,
50
μM)‐induced
F4/80
+
CD11c
phenotype
RAW
264.7
macrophages,
accompanied
by
increased
mRNA
levels
inflammatory
mediators,
antigen‐presenting
genes
(Cd80,
Cd86,
H2‐Aa),
significantly
enhanced
phagocytosis
macrophage.
Meanwhile,
expression
Toll‐like
receptor
4
(TLR4),
co‐receptor
CD14,
leading
significant
activation
downstream
ERK/NF‐κB
pathway.
However,
co‐exposure
cells
TAK‐242,
a
TLR4
inhibitor,
suppressed
TPHP‐induced
phenotype,
down‐regulated
mediators
antigen‐presentation
related
genes,
via
blocked
TLR4/ERK/NF‐κB
Taken
together,
our
suggested
could
induce
macrophage
dysfunction
through
activating
TLR4‐mediated
signaling
pathway,
it
be
reason
health‐threatening
consequences.
Journal of Applied Toxicology,
Год журнала:
2024,
Номер
44(7), С. 965 - 977
Опубликована: Фев. 28, 2024
Abstract
Triphenyl
phosphate
(TPhP)
is
an
organophosphate
flame
retardant
and
plasticizer
that
added
to
a
wide
variety
of
consumer
industrial
products.
It
also
ubiquitous
environmental
pollutant.
Exposure
TPhP
has
been
shown
alter
gene
expression
in
metabolic
estrogenic
signaling
pathways
vitro
vivo
models
species,
as
such,
considered
be
endocrine
disrupting
chemical.
chemicals
increasingly
being
associated
with
changes
the
epigenome,
especially
during
embryonic
development.
The
aim
this
study
was
evaluate
whether
exposure
aquatic
ecosystems
ability
epigenome
two
immortal
cell
lines
derived
from
trout
(
Oncorhynchus
mykiss
).
This
assessed
24
h
resulted
histone
modification
DNA
methylation
profiles
steelhead
cells
rainbow
gill
epithelial
cells.
Results
show
several
epigenetic
modifications
on
H3
are
altered
following
exposure,
but
not
Specifically,
acetylation,
mono‐methylation
global
were
found
reduced.
alterations
these
suggest
fetal
development
may
developing
embryo,
likely
pathways.
impacts
determined
even
carry
multigenerational
detrimental
effects
human
ecosystem
health,
which
requires
further
investigation.
Ecotoxicology and Environmental Safety,
Год журнала:
2025,
Номер
291, С. 117877 - 117877
Опубликована: Фев. 1, 2025
Diabetic
kidney
disease
is
a
significant
complication
of
diabetes
mellitus,
and
exposure
to
certain
chemicals
may
play
role
in
its
development.
Triphenyl
phosphate
(TPHP)
commonly
used
plastics
flame
retardants.
This
study
aims
investigate
the
potential
impact
TPHP
metabolite
diphenyl
(DPHP)
on
diabetic
using
various
methods,
including
network
toxicology,
molecular
docking,
cell
experiments
like
CCK8
assay
real-time-PCR.
The
research
examined
relationship
between
urinary
DPHP
levels
function
American
adults
data
from
National
Health
Nutrition
Examination
Survey
(NHANES)
2017
March
2020.
Additionally,
explored
targets
action
for
toxicity
analysis,
conducted
protein
interaction
functional
aspects
through
Gene
Ontology
Kyoto
Encyclopedia
Genes
Genomes
enrichment
analysis.
Furthermore,
identified
key
proteins
involved
experimental
verification
by
treating
cells
with
DPHP.
Toxicity
analysis
showed
that
could
cause
dose-dependent
mouse
podocyte
clone
5
(MPC5)
mesangial
(MES13).
also
detected
mRNA
expression
core
molecularly
docked
results
indicated
statistically
regulation
most
MPC5,
MES13,
human
kidney-2
cells.