Biofabrication,
Год журнала:
2024,
Номер
16(4), С. 042006 - 042006
Опубликована: Авг. 27, 2024
Abstract
Recent
years
have
seen
the
creation
and
popularization
of
various
complex
in
vitro
models
(CIVMs),
such
as
organoids
organs-on-chip,
a
technology
with
potential
to
reduce
animal
usage
pharma
while
also
enhancing
our
ability
create
safe
efficacious
drugs
for
patients.
Public
awareness
CIVMs
has
increased,
part,
due
recent
passage
FDA
Modernization
Act
2.0.
This
visibility
is
expected
spur
deeper
investment
adoption
models.
Thus,
end-users
model
developers
alike
require
framework
both
understand
readiness
current
enter
drug
development
process,
assess
upcoming
same.
review
presents
selection
based
on
comparative
-omics
data
(which
we
term
model-omics),
metrics
qualification
specific
test
assays
that
may
support
context-of-use
(COU)
assays.
We
surveyed
existing
healthy
tissue
ten
development-critical
organs
body,
provide
evaluations
suggestions
improving
model-omics
COU
each.
In
whole,
this
comes
from
perspective,
seeks
an
evaluation
where
are
poised
maximum
impact
roadmap
realizing
potential.
Environmental Research,
Год журнала:
2022,
Номер
217, С. 114650 - 114650
Опубликована: Окт. 26, 2022
While
human
regulatory
risk
assessment
(RA)
still
largely
relies
on
animal
studies,
new
approach
methodologies
(NAMs)
based
in
vitro,
silico
or
non-mammalian
alternative
models
are
increasingly
used
to
evaluate
chemical
hazards.
Moreover,
epidemiological
studies
with
biomarkers
of
effect
(BoE)
also
play
an
invaluable
role
identifying
health
effects
associated
exposures.
To
move
towards
the
next
generation
(NGRA),
it
is
therefore
crucial
establish
bridges
between
NAMs
and
standard
approaches,
processes
for
increasing
mechanistically-based
biological
plausibility
studies.
The
Adverse
Outcome
Pathway
(AOP)
framework
constitutes
important
tool
address
these
needs
but,
despite
a
significant
increase
knowledge
awareness,
use
AOPs
RA
remains
limited.
objective
this
paper
issues
related
using
context
from
various
perspectives
as
was
discussed
workshop
organized
within
European
Union
partnerships
HBM4EU
PARC
spring
2022.
presents
examples
where
AOP
has
been
proven
useful
process,
particularly
hazard
prioritization
characterization,
integrated
approaches
testing
(IATA),
identification
validation
BoE
Nevertheless,
several
limitations
were
identified
that
hinder
optimal
usability
acceptance
by
community
including
lack
quantitative
information
response-response
relationships
efficient
ways
map
data
(exposure
toxicity)
onto
AOPs.
summarizes
suggestions,
ongoing
initiatives
third-party
tools
may
help
overcome
obstacles
thus
assure
better
implementation
NGRA.
Trends in Food Science & Technology,
Год журнала:
2023,
Номер
133, С. 277 - 290
Опубликована: Фев. 8, 2023
New
Approach
Methodologies
(NAMs)
comprise
in
silico
and
vitro
methods
applied
as
alternative
to
animal
testing.
Even
though
NAMs
are
already
fully
implemented
research
tools,
their
use
regulatory
risk
assessments
(RA)
is
limited
currently.
To
promote
the
uptake/acceptance
of
NAMs,
a
paradigm
shift
assessment
approaches,
proper
dialogue
between
assessors
managers
needed.
Several
reviews
addressed
for
chemical
RA
generic
terms,
but
without
providing
specific
considerations
on
food/feed
safety
assessments.
Therefore,
this
review,
we
give
insights
potential
purposes
EU.
We
summarise
relevant
projects
activities
coordinated
by
European
Food
Safety
Authority
(EFSA),
which
agency
Union
that
contributes
food
feed
chain.
The
review
informs
future
developments
human
health
RA,
touches
protein
toxicity
allergenicity,
well
environmental
risks.
Reducing
testing
filling
some
gaps
via
almost
reality.
Moreover,
there
growing
body
evidence
confirming
inclusion
mechanistic
information
improves
EFSA's
address
main
challenge
using
intermediate
effects
observed
non-animal
models
assessments,
especially
those
linked
adverse
insufficiently
covered
or
uncovered
apical
endpoints.
Archives of Toxicology,
Год журнала:
2022,
Номер
96(7), С. 1935 - 1950
Опубликована: Май 3, 2022
Abstract
Alternative
methods
to
animal
use
in
toxicology
are
evolving
with
new
advanced
tools
and
multilevel
approaches,
answer
from
one
side
3Rs
requirements,
on
the
other
offering
relevant
valid
tests
for
drugs
chemicals,
considering
also
their
combination
test
strategies,
a
proper
risk
assessment.
While
stand-alone
methods,
have
demonstrated
be
applicable
some
specific
toxicological
predictions
limitations,
strategy
application
of
New
Approach
Methods
(NAM),
solve
complex
endpoints
is
addressed
by
Integrated
Approaches
Testing
Assessment
(IATA),
aka
Strategies
(ITS)
or
Defined
(DA).
The
central
challenge
evidence
integration
shared
needs
assessment
systematic
reviews
an
evidence-based
Toxicology.
Increasingly,
machine
learning
(aka
Artificial
Intelligence,
AI)
lends
itself
integrate
diverse
streams.
In
this
article,
we
give
overview
state
art
alternative
IATA
regulatory
various
hazards,
outlining
future
orientation
perspectives.
We
call
leveraging
synergies
integrated
approaches
vivo,
vitro
silico
as
true
vivitrosi.
Trends in Food Science & Technology,
Год журнала:
2023,
Номер
134, С. 98 - 111
Опубликована: Фев. 3, 2023
The
risk
assessment
of
small
particles
(including
nanoparticles)
in
products
used
the
food
chain
EU
falls
within
remit
European
Food
Safety
Authority
(EFSA)
and
has
been
under
thorough
scientific
considerations
for
over
a
decade.
Now
that
more
experience
is
gained
with
evaluating
novel
foods,
contact
materials,
food/feed
additives
pesticides,
outlines
regulatory
safety
assessments
data
requirements
are
established.
This
paper
reviews
principles
underlying
testing
particles,
referring
to
two
recently
published
EFSA
guidance
documents.
Examples
observations
from
assessing
existing
materials
provided
facilitate
wider
readership
adequate
implementation
requirements.
starting
point
physicochemical
characterisation
pristine
material,
being
an
engineered
nanomaterial,
nanostructured
material
or
conventional
contains
fraction
may
retain
properties
at
nanoscale.
Key
parameters
threshold
values
establishing
presence
techniques
methods
complex
matrices,
as
well
approaches
dietary
exposure
outlined.
Where
there
likelihood
remaining
after
gastrointestinal
digestion,
hazard
identification
required
special
provisions.
In
particular,
certain
nano-specific
highlighted
have
be
considered
during
toxicological
aim
demonstrate
consumer
Europe.
International Journal of Molecular Sciences,
Год журнала:
2023,
Номер
24(6), С. 5682 - 5682
Опубликована: Март 16, 2023
Endometriosis
is
an
estrogen-dependent
gynecologic
illness
that
has
long-term
effects
on
a
woman’s
fertility,
physical
health,
and
overall
quality
of
life.
Growing
evidence
suggests
endocrine-disrupting
chemicals
(EDCs)
may
be
etiologically
involved
in
the
development
severity
disease.
We
consider
available
human
EDCs
endometriosis,
limiting
ourselves
to
studies
have
individually
assessed
chemical
amounts
women.
Dioxins,
BPA,
Phthalates,
other
endocrine
disruptors,
like
DDT,
are
among
indicating
environmental
etiology
for
endometriosis.
Collectively,
this
review
describes
how
toxins
linked
lower
fertility
women,
as
well
number
reproductive
diseases,
focusing
pathology
endometriosis
its
treatments.
Importantly,
can
used
investigate
techniques
preventing
negative
EDC
exposure.
Environment International,
Год журнала:
2024,
Номер
188, С. 108772 - 108772
Опубликована: Май 23, 2024
Perfluoroalkyl
substances
(PFAS)
have
been
identified
in
various
products
that
come
contact
with
human
skin,
ranging
from
school
uniforms
to
personal
care
products.
Despite
this,
knowledge
on
dermal
uptake
of
PFAS
is
lacking.
Thus,
the
absorption
17
was
assessed,
for
first
time,
using
vitro
3D-human
skin
equivalent
models
exposed
500
ng/cm
Cosmetics,
Год журнала:
2021,
Номер
8(2), С. 50 - 50
Опубликована: Июнь 11, 2021
Cosmetic
products
need
to
have
a
proven
efficacy
combined
with
comprehensive
toxicological
assessment.
Before
the
current
regulation
N°1223/2009,
7th
Amendment
European
Cosmetics
Directive
has
banned
animal
testing
for
cosmetic
and
ingredients
in
2004
2009,
respectively.
An
increasing
number
of
alternatives
been
developed
validated
safety
ingredients.
For
example,
2D
cell
culture
models
derived
from
human
skin
can
be
used
evaluate
anti-inflammatory
properties,
or
predict
sensitization
potential;
3D
equivalent
are
irritation
excised
is
as
gold
standard
evaluation
dermal
absorption.
The
aim
this
manuscript
give
an
overview
main
vitro
ex
vivo
alternative
focus
on
regulatory
requirements,
genotoxicity
potential,
eye
irritation,
endocrine
Advantages
limitations
each
model
discussed
novel
technologies
capable
addressing
these
presented.
Computational Toxicology,
Год журнала:
2022,
Номер
21, С. 100213 - 100213
Опубликована: Янв. 7, 2022
In
silico
tools
and
resources
are
now
used
commonly
in
toxicology
to
support
the
"Next
Generation
Risk
Assessment"
(NGRA)
of
cosmetics
ingredients
or
materials.
This
review
provides
an
overview
approaches
that
applied
assess
exposure
hazard
a
cosmetic
ingredient.
For
both
exposure,
databases
existing
information
routinely.
addition,
for
include
use
rules
thumb
systemic
bioavailability
as
well
physiologically-based
kinetics
(PBK)
multi-scale
models
estimating
internal
at
organ
tissue
level.
(Internal)
Thresholds
Toxicological
Concern
applicable
safety
assessment
low
concentrations.
The
structural
rules,
(Quantitative)
Structure-Activity
Relationships
((Q)SARs)
read-across
most
typically
modelling
predict
hazard.
Data
from
increasingly
being
brought
together
NGRA
provide
overall
All
reviewed
terms
their
maturity
robustness
use.