Ecotoxicology and Environmental Safety,
Journal Year:
2023,
Volume and Issue:
263, P. 115348 - 115348
Published: Aug. 17, 2023
Organophosphate
flame
retardants
(OPFRs)
are
environmental
pollutants
of
increasing
interest,
widely
distributed
in
the
environment
and
exerting
possible
deleterious
effects
towards
human
health.
The
present
study
investigates
vitro
their
interactions
with
drug
transporters,
which
targets
for
chemicals
actors
toxicokinetics.
Some
OPFRs,
i.e.,
tris(2-butoxyethyl)
phosphate
(TBOEP),
tris(1,3-dichloroisopropyl)
(TDCPP),
tri-o-cresyl
(TOCP)
triphenyl
(TPHP),
were
found
to
inhibit
activities
some
such
as
organic
anion
transporter
3
(OAT3),
transporting
polypeptide
(OATP)
1B1,
OATP1B3,
cation
2
(OCT2)
or
breast
cancer
resistance
protein
(BCRP).
These
concentration-dependent,
IC50
values
ranging
from
6.1
µM
(for
TDCPP-mediated
inhibition
OCT2)
51.4
TOCP-mediated
BCRP).
OPFRs
also
blocked
transporter-dependent
membrane
passage
endogenous
substrates,
notably
that
hormones.
OAT3
however
failed
transport
TBOEP
TPHP.
additionally
repressed
mRNA
expressions
transporters
cultured
hepatic
HepaRG
cells,
especially
those
OAT2
OCT1
response
TOCP,
2.3
2.5
µM,
respectively.
data
therefore
add
expanding
list
interacting
even
if
OPFR
concentrations
required
impact
2–50
range,
rather
higher
than
observed
humans
environmentally
dietarily
exposed
these
chemicals.
Environmental Science & Technology,
Journal Year:
2023,
Volume and Issue:
57(11), P. 4454 - 4463
Published: March 3, 2023
Liquid
crystal
monomers
(LCMs)
are
indispensable
materials
in
liquid
displays,
which
have
been
recognized
as
emerging
persistent,
bioaccumulative,
and
toxic
organic
pollutants.
Occupational
nonoccupational
exposure
risk
assessment
suggested
that
dermal
is
the
primary
route
for
LCMs.
However,
bioavailability
possible
mechanisms
of
to
LCMs
via
skin
absorption
penetration
remain
unclear.
Herein,
we
used
EpiKutis
3D-Human
Skin
Equivalents
(3D-HSE)
quantitatively
assess
percutaneous
nine
LCMs,
were
detected
e-waste
dismantling
workers'
hand
wipes
with
high
detection
frequencies.
higher
log
Kow
greater
molecular
weight
(MW)
more
difficult
penetrate
through
skin.
Molecular
docking
results
showed
ABCG2
(an
efflux
transporter)
may
be
responsible
These
suggest
passive
diffusion
active
transport
involved
across
barrier.
Furthermore,
occupational
risks
evaluated
based
on
factor
underestimation
continuous
LCMs'
health
previously.
Environment International,
Journal Year:
2023,
Volume and Issue:
172, P. 107749 - 107749
Published: Jan. 13, 2023
Triphenyl
phosphate
(TPHP)
is
a
widely
used
flame
retardant
and
plasticizer
has
been
detected
extensively
in
environmental
media,
wildlife
human
bodies.
Several
epidemiological
animal
studies
have
revealed
that
TPHP
exposure
positively
associated
with
glucose
homeostasis
disruption
diabetes.
However,
the
effects
of
on
hepatic
underlying
mechanisms
remain
unclear.
The
present
work
aimed
to
investigate
cytotoxicity
metabolism
its
metabolite
diphenyl
(DPHP)
within
hepatocytes.
cell
viability
assay
undertaken
normal
liver
(L02)
cells
showed
exhibited
more
potent
hepatotoxicity
than
DPHP.
RNA
sequencing
(RNA-seq)
data
DPHP
presented
different
modes
toxic
action.
Insulin
resistance
one
predominant
toxicities
for
TPHP,
but
not
insulin-stimulated
uptake
glycogen
synthesis
were
impaired
by
while
no
significant
impairment
these
factors.
induced
endoplasmic
reticulum
(ER)
stress,
ER
stress
antagonist
4-PBA
restored
TPHP.
could
also
induce
insulin
mice.
Taken
together,
results
suggested
induces
through
Environmental Science & Technology,
Journal Year:
2023,
Volume and Issue:
57(4), P. 1764 - 1775
Published: Jan. 2, 2023
The
ability
to
accurately
assess
the
health
risks
of
contaminants
is
limited
by
shortcomings
toxicological
standards.
Using
organophosphate
esters
(OPEs)
as
an
example,
this
study
attempted
integrate
physiologically
based
pharmacokinetic
(PBPK)-based
forward
dosimetry
and
in
vitro
bioassays
likelihood
inducing
biological
effects
humans.
total
exposure
level
OPEs
for
Chinese
residents
was
19.5
±
8.71
ng/kg/day
with
inhalation
being
main
pathway.
Then,
human
PBPK
models
were
developed
individual
predict
their
steady-state
concentrations
tissues,
predicted
median
levels
blood
close
measurements.
reference
doses
(RfDs)
on
comparable
vivo
animal-derived
RfDs,
demonstrating
reliability
bioassays.
Therefore,
bioactivities
humans
(RQin-vitro)
calculated
using
toxicity
data
OPE
tissues.
RQin-vitros
tris(2-chloroisopropyl)
phosphate,
tris(1,3-dichloropropyl)
triphenyl
phosphate
(7.68
×
10–5–3.18
10–3)
assessed
traditional
RfDs
(5.22
10–5–1.94
10–3),
indicating
credibility
method
proposed
study.
This
establishes
a
new
framework
improve
risk
assessment
without
sufficient
minimize
need
animal
experimentation.
