Chemical risk assessment in food animals via physiologically based pharmacokinetic modeling − Part I: Veterinary drugs on human food safety assessment
Environment International,
Год журнала:
2025,
Номер
197, С. 109339 - 109339
Опубликована: Фев. 18, 2025
Язык: Английский
TKPlate 1.0: An Open‐access platform for toxicokinetic and toxicodynamic modelling of chemicals to implement new approach methodologies in chemical risk assessment
EFSA Journal,
Год журнала:
2023,
Номер
21(11)
Опубликована: Ноя. 1, 2023
This
publication
is
linked
to
the
following
EFSA
Supporting
Publications
articles:
http://onlinelibrary.wiley.com/doi/10.2903/sp.efsa.2023.EN-8441/full,
http://onlinelibrary.wiley.com/doi/10.2903/sp.efsa.2023.EN-8440/full,
http://onlinelibrary.wiley.com/doi/10.2903/sp.efsa.2023.EN-8437/full
Язык: Английский
Countdown to 2027 – maximising use of NAMs in food safety assessment: closing the gap for regulatory assessments in Europe
Regulatory Toxicology and Pharmacology,
Год журнала:
2025,
Номер
unknown, С. 105863 - 105863
Опубликована: Май 1, 2025
Язык: Английский
User Guide for TKPlate 1.0: An open access platform for implementing new approach methodologies in chemical risk assessment through toxicokinetic and toxicodynamic modelling
EFSA Supporting Publications,
Год журнала:
2023,
Номер
20(11)
Опубликована: Ноя. 1, 2023
This
technical
report
provides
a
user
guide
for
the
TKPlate
1.0
platform
which
allows
to
implement
New
Approach
Methodologies
in
chemical
risk
assessment
process
by
means
of
toxicokinetic
and
toxicodynamic
modelling
chemicals
humans,
laboratory
animals,
farm
animals
species
ecological
relevance.
is
available
as
an
open
access
web-based
tool
or
downloadable
application.
The
built
workflow
7
modules:
1.
Input
module
can
select
species,
kinetic
physiologically-based
model,
be
modelled,
exposure
scenarios
simulation
times,
2.
Forward
dosimetry
allowing
simulate
parameters,
body
fluid
organ
concentrations,
3.
Reverse
reconstruction
distributions
using
internal
dose
such
biomonitoring
data,
4.
Benchmark
model
averaging
on
basis,
5.
Dynamic
energy
budget
modelling,
6.
Mixture
characterisation
methods
from
EFSA's
Scientific
committee
guidance
document,
7.
Automated
where
input
output
data
report,
graphs
datasets.
For
each
module,
structure
applications
are
described
with
examples.
development
external
scientific
associated
EFSA
editorial
two
reports
namely
case
studies
illustrating
1.0.
Finally,
all
models
files
also
published
Zenodo
(https://zenodo.org/record/7494936).
Язык: Английский
Metabolites in the regulatory risk assessment of pesticides in the EU
Frontiers in Toxicology,
Год журнала:
2023,
Номер
5
Опубликована: Дек. 19, 2023
A
large
majority
of
chemicals
is
converted
into
metabolites
through
xenobiotic-metabolising
enzymes.
Metabolites
may
present
a
spectrum
characteristics
varying
from
similar
to
vastly
different
compared
with
the
parent
compound
in
terms
both
toxicokinetics
and
toxicodynamics.
In
pesticide
arena,
role
metabolism
increasingly
recognised
as
significant
factor
particularly
for
design
interpretation
mammalian
toxicological
studies
toxicity
assessment
pesticide/metabolite-associated
issues
hazard
characterization
risk
purposes,
including
parts
various
residues
ecotoxicological
adversities.
This
particular
relevance
that
are
unique
humans
comparison
found
vitro
or
vivo
animal
studies,
but
also
disproportionate
(quantitative
differences)
between
species.
Presence
underlie
potential
concerns.
review
aims
current
state-of-the-art
comparative
research
assessment,
One
Health
perspectives,
future
needs
based
on
experiences
gained
at
European
Food
Safety
Authority.
Язык: Английский
Application of a generic PBK model for beef cattle: Tissue/fluid correlations of paracetamol and NSAIDs
Food and Chemical Toxicology,
Год журнала:
2024,
Номер
190, С. 114812 - 114812
Опубликована: Июнь 13, 2024
Nonsteroidal
Anti-Inflammatory
Drugs
(NSAIDs)
and
paracetamol
can
be
administered
off-label
to
cattle.
Since
the
use
of
these
veterinary
medicines
in
cattle
may
pose
a
public
health
risk
after
meat
consumption,
it
is
important
translate
measured
concentrations
urine
tissues
into
for
human
consumption.
A
generic
physiologically-based
kinetic
(PBK)
model
enable
this
translation.
In
work,
beef
PBK
was
applied
calculate
relationships
between
different
bovine
those
were
compared
matrices.
Sixty-seven
kidney
samples,
corresponding
available
19
serum
samples
analysed.
Overall,
70%
predictions
are
within
2-fold
factor
kidney/meat,
urine/meat,
plasma/meat
ratios
established.
The
conversions
mostly
two,
while
based
on
plasma
underpredicted.
Based
ratios,
could
used
as
an
appropriate
surrogate
matrix
fast,
simple
vivo
sample
screening
test
under
field
conditions,
such
local
farms
slaughterhouses,
predict
maximum
residue
level
exceedance
meat,
reducing
number
samples.
Язык: Английский
Application of partition coefficient methods to predict tissue:plasma affinities in common farm animals: Influence of ionisation state
Toxicology Letters,
Год журнала:
2024,
Номер
398, С. 140 - 149
Опубликована: Июнь 24, 2024
Tissue
affinities
are
conventionally
determined
from
in
vivo
steady-state
tissue
and
plasma
or
plasma-water
chemical
concentration
data.
In
silico
approaches
were
initially
developed
for
preclinical
species
but
standardly
applied
tested
human
physiologically-based
kinetic
(PBK)
models.
Recently,
generic
PBK
models
farm
animals
have
been
made
available
require
partition
coefficients
as
input
parameters.
the
current
investigation,
data
species-specific
compositions
collected,
prediction
of
distribution
various
tissues
livestock
cattle,
chicken,
sheep
swine
performed.
Overall,
composition
was
very
similar
across
four
animal
species.
However,
small
differences
observed
moisture,
fat
protein
content
organs
within
each
Such
could
be
attributed
to
factors
such
variations
age,
breed,
weight
general
conditions
itself.
With
regards
predictions
tissue:plasma
coefficients,
80
%,
71
77
%
model
a
factor
10
using
methods
Berezhkovskiy
(2004),
Rodgers
Rowland
(2006)
Schmitt
(2008).
The
method
(2004)
often
providing
most
reliable
except
swine,
where
(2008)
performed
best.
addition,
investigation
impact
classes
on
performance,
all
had
reliability.
Notwithstanding,
no
clear
pattern
regarding
specific
chemicals
detected
values
predicted
outside
10-fold
change
certain
tissues.
This
manuscript
concludes
with
need
future
research,
particularly
focusing
lipophilicity
binding.
Язык: Английский
New Approach Methodologies (NAMs) to Support Regulatory Decisions for Chemical Safety
Letizia Carramusa,
Wilfrieda Mune,
Neil Hunt
и другие.
FSA research and evidence.,
Год журнала:
2024,
Номер
unknown
Опубликована: Сен. 10, 2024
Язык: Английский
Applications of TKPlate 1.0 for toxicokinetic and toxicodynamic modelling of chemicals: Case Studies
EFSA Supporting Publications,
Год журнала:
2023,
Номер
20(11)
Опубликована: Ноя. 1, 2023
This
technical
report
is
associated
with
the
external
scientific
and
user
guide
of
TKPlate
1.0
provides
case
studies
for
each
modules
performing
either
toxicokinetic
and/or
toxicodynamic
modelling.
For
study,
input
data
are
provided
procedure
to
run
them
described
can
be
uploaded
from
info
page
module.
The
presented
here
include
forward
dosimetry,
reverse
modelling,
dynamic
energy
budget
modelling
risk
characterisation
combined
exposure
multiple
chemicals
MIXTOX
four
fipronil
(human
one-compartment
kinetic
model),
caffeine
amiodarone
(generic
human
physiologically-based
(PBK)
chlorpyrifos
(QIVIVE
generic
PBK
model)
a
study
using
multi-route
6
compartment
model.
two
available
namely
melatonin
model
deltamethrin
chicken
laying
hens.
Both
allow
reconstruction
plausible
distributions
internal
dose
such
as
biomonitoring
data.
TD
90-day
toxicological
in
male
rats
illustrated
perform
benchmark
presented.
individual
population
effects
fenvalerate
on
Daphnia
magna
survival
lead
Eisenia
fetida
growth.
Finally,
mixture
three
contaminants
deterministic
hazard
index
methodology.
Язык: Английский
Roadmap for action for advancing aggregate exposure to chemicals in the EU
EFSA Supporting Publications,
Год журнала:
2024,
Номер
21(7)
Опубликована: Июль 1, 2024
Abstract
The
European
Food
Safety
Authority
(EFSA)
has
a
goal
to
efficiently
conduct
aggregate
exposure
assessments
(AEAs)
for
chemicals
using
both
models
and
human
biomonitoring
(HBM)
data
by
2030.
To
achieve
EFSA's
vision,
roadmap
action
advancing
(AE)
in
the
EU
was
developed.
This
created
performing
series
of
engagement
collection
activities
map
currently
available
methods,
data,
tools
assessing
AE
chemicals,
against
needs
priorities
EFSA.
allowed
creation
AEA
framework,
identification
knowledge
gaps
our
current
capabilities,
challenges
blockers
that
would
hinder
efforts
fill
gaps.
identifies
interdependent
working
areas
(WAs)
where
additional
research
development
are
required
goal.
It
also
proposes
future
collaboration
opportunities
recommends
several
project
proposals
meet
goals.
Eight
proposal
projects
supported
SWOT
analysis
presented
consideration.
inform
high‐level
recommendations
multi‐annual
multi‐partner
projects.
Recommendations
improve
stakeholder
communication
work
on
were
gathered
surveying
stakeholders
specific
actions
AE,
including
webinars,
virtual
training,
social
media
channels,
newsletters.
Язык: Английский