Environment International,
Journal Year:
2024,
Volume and Issue:
190, P. 108868 - 108868
Published: July 2, 2024
As
alternatives
of
perfluorooctanoic
acid
(PFOA),
hexafluoropropylene
oxide
dimeric
(HFPO-DA)
and
trimeric
(HFPO-TA)
have
been
detected
increasingly
in
environmental
media
even
humans.
They
shown
to
exhibit
reproductive
toxicity
model
species,
but
their
effects
on
human
remain
unclear
due
the
knowledge
gap
mode
action.
Herein,
(anti-)androgenic
two
HFPOs
PFOA
were
investigated
underlying
toxicological
mechanism
was
explored
by
combining
zebrafish
test,
cell
assay
molecular
docking
simulation.
Exposure
juvenile
chemicals
during
sex
differentiation
promoted
feminization,
with
HFPO-TA
acting
at
an
concentration
1
μg/L.
The
inhibited
proliferation
prostate
cells
transcriptional
activity
androgen
receptors
(AR),
displaying
strongest
potency.
Molecular
revealed
that
bind
AR
a
conformation
similar
known
antagonist.
Combined
vivo,
vitro
silico
results
demonstrated
disrupted
likely
antagonizing
AR-mediated
pathways,
provided
more
evidence
is
not
safe
alternative
PFOA.
Eco-Environment & Health,
Journal Year:
2024,
Volume and Issue:
3(4), P. 476 - 493
Published: Aug. 30, 2024
Per-
and
polyfluoroalkyl
substances
(PFAS)
are
endocrine
disruptors
with
unambiguous
neurotoxic
effects.
However,
due
to
variability
in
experimental
models,
population
characteristics,
molecular
endpoints,
the
elucidation
of
mechanisms
underlying
PFAS-induced
neurotoxicity
remains
incomplete.
In
this
review,
we
utilized
adverse
outcome
pathway
(AOP)
framework,
a
comprehensive
tool
for
evaluating
toxicity
across
multiple
biological
levels
(molecular,
cellular,
tissue
organ,
individual,
population),
elucidate
induced
by
PFAS.
Based
on
271
studies,
reactive
oxygen
species
(ROS)
generation
emerged
as
initiating
event
1
(MIE1).
Subsequent
key
events
(KEs)
at
cellular
level
include
oxidative
stress,
neuroinflammation,
apoptosis,
altered
Ca
Hexafluoropropylene
oxide
trimer
acid
(HFPO-TA,
C2F5(CF2OCF(CF3))2COOH)
is
widely
used
as
an
alternative
to
perfluorooctanoic
(PFOA),
but
whether
it
a
safe
requires
further
evaluation.
In
this
study,
male
mice
were
exposed
three
dosages
(0.56,
2.8,
and
14
mg/kg)
of
HFPO-TA
via
single
oral
gavage
or
intravenous
injection
for
28
days.
was
rapidly
absorbed
into
the
blood
tissues
within
15
min
postexposure,
with
volume
distribution
approximately
3
times
higher
than
PFOA,
indicating
greater
propensity
tissue
distribution.
Notably,
distinctly
more
accumulated
in
liver
compared
plasma
other
very
poorly
excreted,
only
2.23%
urine
7.26%
feces
on
21st
day
after
exposure.
A
physiologically
based
toxicokinetic
model,
extrapolated
long-term
low-dose
exposure,
revealed
lower
bile
clearance
rate
(8-fold)
partition
coefficient
(7-fold)
hepatic
first-pass
effect
(5-fold)
contributing
its
remarkable
accumulation
(5-fold).
Molecular
docking
analysis
reveals
strong
binding
affinity
typical
enterohepatic
circulation
transport
proteins
due
hydrophobicity,
flexible
chain
structure,
formation
additional
hydrogen
bonds,
favoring
liver.
The
results
suggest
that
may
not
be
substitute
legacy
PFAS,
human
exposure
risk
assessments
are
warranted.
