Determination of the Zebrafish Embryo Developmental Toxicity Assessment (ZEDTA) as an Alternative Non-Mammalian Approach for the Safety Assessment of Agrochemicals.
Reproductive Toxicology,
Год журнала:
2025,
Номер
unknown, С. 108837 - 108837
Опубликована: Янв. 1, 2025
Язык: Английский
Threading the Eye of the Needle: Designing the Next Generation of Crop Protection Solutions in an Increasingly Deglobalized Regulatory Landscape
Reza J. Rasoulpour,
Ashish Batra,
Guomin Shan
и другие.
Journal of Agricultural and Food Chemistry,
Год журнала:
2025,
Номер
73(3), С. 1801 - 1803
Опубликована: Янв. 22, 2025
The
growing
global
needs
for
food
and
feed
the
impact
of
climate
change
on
agriculture
demand
innovative
sustainable
solutions
to
protect
against
crop
losses
improve
yields
worldwide.
To
facilitate
timely
discovery
development
new
protection
products
with
favorable
human
health
environmental
safety
profiles,
approach
methodologies
(NAMs)
is
essential
predict
potential
risk
perform
assessment
early
in
process.
Significant
advances
NAM
research
have
been
made
recent
years.
We
organized
a
Virtual
Special
Issue
invited
submissions
seven
high-quality
articles
reviews
latest
emerging
NAMs
predictive
agrochemical
development.
Here
we
provide
an
introductory
overview
need
innovation
novel
agricultural
highlight
findings
from
each
article
this
special
edition.
Язык: Английский
Cell Painting and Chemical Structure Read-Across Can Complement Each Other for Rat Acute Oral Toxicity Prediction in Chemical Early Derisking
F. Camilleri,
J. Wenda,
C. Pecoraro-Mercier
и другие.
Chemical Research in Toxicology,
Год журнала:
2024,
Номер
37(11), С. 1851 - 1866
Опубликована: Ноя. 8, 2024
Early
derisking
decisions
in
the
development
of
new
chemical
compounds
enable
identification
novel
candidates
with
improved
safety
profiles.
In
vivo
studies
are
traditionally
conducted
early
assessment
acute
oral
toxicity
crop
protection
products
to
avoid
compounds,
which
considered
"very
acutely
toxic",
an
lethal
dose
50%
(LD50)
≤
60
mg/kg
body
weight.
Those
lengthy
and
costly
raise
ethical
concerns,
catalyzing
use
nonanimal
alternatives.
The
objective
our
analysis
was
assess
predictive
efficacy
read-across
approaches
for
rats,
comparing
structure
information,
vitro
biological
data
derived
from
Cell
Painting
profiling
assay
on
U2OS
cells,
or
combination
both.
Our
findings
indicate
that
classification
as
very
toxic
(LD50
mg/kg)
not
is
possible
using
a
approach,
morphological
profiles,
When
classifying
structurally
similar
those
training
set,
more
(balanced
accuracy
0.82).
Conversely,
when
be
classified
were
different
profiles
0.72).
Combining
two
models
allowed
set
slightly
improve
predictions
0.85).
Язык: Английский
Cell Painting and chemical structure read-across can complement each other for rat acute oral toxicity prediction in chemical early de-risking
F. Camilleri,
J. Wenda,
C. Pecoraro-Mercier
и другие.
bioRxiv (Cold Spring Harbor Laboratory),
Год журнала:
2024,
Номер
unknown
Опубликована: Апрель 28, 2024
ABSTRACT
Early
de-risking
decisions
in
the
development
of
new
chemical
compounds,
enable
identification
novel
candidates
with
improved
safety
profiles.
In
vivo
studies
are
traditionally
conducted
early
assessment
acute
oral
toxicity
crop
protection
products
to
avoid
compounds
which
considered
“very
acutely
toxic”,
an
Lethal
Dose
50%
(LD50)
≤
60
mg/kg
bodyweight.
Those
lengthy,
costly,
and
raise
ethical
concerns,
catalyzing
use
non-animal
alternatives.
The
objective
our
analysis
was
assess
predictive
efficacy
read-across
approaches
for
rats,
comparing
structure
information,
vitro
biological
data
derived
from
Cell
Painting
profiling
assay
on
U2OS
cells
or
combination
both.
Our
findings
indicate
that
classification
as
very
toxic
(LD50
mg/kg)
not
is
possible
using
a
approach,
morphological
profiles,
When
classifying
structurally
similar
those
training
set,
more
(balanced
accuracy
0.82).
Conversely,
when
be
classified
were
different
profiles
0.72).
Combining
two
models
allowed
slightly
improve
predictions
0.85).
Abstract
Figure
For
Table
Contents
Only
Язык: Английский
Derisking Future Agrochemicals before They Are Made: Large-Scale In Vitro Screening for In Silico Modeling of Thyroid Peroxidase Inhibition
Martin Adamczewski,
Britta Nisius,
Nina Kausch‐Busies
и другие.
Chemical Research in Toxicology,
Год журнала:
2024,
Номер
unknown
Опубликована: Сен. 20, 2024
Inhibition
of
thyroid
peroxidase
(TPO)
is
a
known
molecular
initiating
event
for
hormone
dysregulation
and
toxicity.
Consequently,
TPO
critical
off-target
the
design
safer
agrochemicals.
To
date,
fewer
than
500
structurally
characterized
inhibitors
are
known,
most
comprehensive
result
set
generated
under
identical
conditions
encompasses
approximately
1000
compounds
from
subset
ToxCast
compound
collection.
Here
we
describe
collaboration
between
wet
lab
data
scientists
combining
large
in
vitro
screen
subsequent
development
an
silico
model
predicting
inhibition.
The
encompassed
more
100,000
diverse
drug-like
agrochemical
yielded
6000
novel
inhibitors.
On
this
foundation,
applied
different
machine
learning
techniques
compared
their
performance.
We
discuss
use
cases
models
research
explain
that
recall
particular
importance
when
selecting
virtual
collections.
Furthermore,
show
due
to
higher
structural
diversity
our
training
data,
final
allowed
better
generalization
trained
on
set.
now
have
tool
predict
inhibition
even
molecules
only
available
virtually,
such
as
hits
screenings,
or
consideration
inclusion
screening
Structures
activity
34,524
provided.
This
includes
almost
all
inhibitors,
including
3000
proprietary
structures,
proportion
inactives.
Язык: Английский