N-(1,3-Dimethylbutyl)-N′-phenyl-1,4-phenylenediamine
(6PPD)
and
its
oxidation
product
6PPD-quinone
(6PPDQ)
showed
different
acute
toxicities
bioaccumulation
potencies
in
fish.
In
this
study,
we
compared
the
thyroid
disrupting
effects
of
6PPD
6PPDQ
through
vitro,
silico,
vivo
assays.
Interestingly,
although
similar
docking
affinities
with
hormone
receptor
(TR)
isoforms
GH3
cell
inhibition
effects,
signaling
pathway,
eye
development,
phototactic
behaviors,
density
retinal
layer
larval
zebrafish
were
significantly
affected
only
following
exposure.
Further
investigation
demonstrates
that
can
act
as
a
TR
antagonist
to
reduce
opsin
protein
abundance
inhibit
cone
photoreceptor
proliferation,
which
finally
alters
structure
causes
microphthalmus
zebrafish.
Especially,
under
environmental
relevant
concentration
exposure,
induced
alterations
trβ,
opn1lw1,
opn1mw1,
rpe65a,
nr2e3
gene
expressions
no
significant
histopathological
change
was
observed.
This
study
illustrates
for
first
time
more
serious
visual
system
impairment
6PPDQ,
disruption
being
contributing
factor,
while
other
important
toxic
targets
still
require
further
research.
N-(1,3-Dimethylbutyl)-N′-phenyl-1,4-phenylenediamine
(6PPD)
and
its
oxidation
product
6PPD-quinone
(6PPDQ)
showed
different
acute
toxicities
bioaccumulation
potencies
in
fish.
In
this
study,
we
compared
the
thyroid
disrupting
effects
of
6PPD
6PPDQ
through
vitro,
silico,
vivo
assays.
Interestingly,
although
similar
docking
affinities
with
hormone
receptor
(TR)
isoforms
GH3
cell
inhibition
effects,
signaling
pathway,
eye
development,
phototactic
behaviors,
density
retinal
layer
larval
zebrafish
were
significantly
affected
only
following
exposure.
Further
investigation
demonstrates
that
can
act
as
a
TR
antagonist
to
reduce
opsin
protein
abundance
inhibit
cone
photoreceptor
proliferation,
which
finally
alters
structure
causes
microphthalmus
zebrafish.
Especially,
under
environmental
relevant
concentration
exposure,
induced
alterations
trβ,
opn1lw1,
opn1mw1,
rpe65a,
nr2e3
gene
expressions
no
significant
histopathological
change
was
observed.
This
study
illustrates
for
first
time
more
serious
visual
system
impairment
6PPDQ,
disruption
being
contributing
factor,
while
other
important
toxic
targets
still
require
further
research.
