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AR226-2714
AR226-2714
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CONSIDERATIONS RELEVANT TO CONSTRUCTING A HUMAN PBPK
MODEL FOR PERFUJOROOCTANOXCACID (PFOA)
D. Paustentiach1; G. Jepson2
1.
ChemRtsk,
San
Francisco, CA, USA. Molecular Toxicology,
Haskell
Laboratory
for
Health
and
2.
Biochemical
and Sciences,
Newark,
DE,
USA.
Environmental
Perfluorooctanolc
add
(PFOA)
is a
surfactant,
which
has
received significant blood samples from
Interest
In
recent
years due to its reported prevalence in Consequently, there has been some activity
associated
with
many US citizens. constructing a human
PBPK
model
to
relate
inhalation
and
oral exposures to studies conducted
on
PFOA
levels
in
plasma.
While there have been many kinetic data have not been useful in extrapolation
to
PFOA
rodents,
the
rodent
kinetic There are
several
considerations
relevant
to
the
construction
kinetics in humans. of a human P8PK model
that
will
determine
how,
or
even
If,
such a model is which will affect
PFOA. First, PFOA Is a
surface-active chemical, has thus far complicated any efforts to
appropriate for
Its
behavior
in
biological
systems and partition coefficients.
Second,
PFOA
is
reported
to
be
determine
tissue to blood In mammalian
systems,
thereby
eliminating
the
need
for
explicit
unmetabollzed description of metabolizing
organs
or
tissues.
Third,
the elimination rate is The reported half-life
In
dramaticallaypdpirfofexriemnat tbeelytw4eyeenahrsumasancsomanpdarreoddteont2s.hours in the female rat.
humans Further,
Is
rats
have
sex
dependent
elimination
rates,
which do not appear to be to PFOA are lacking;
to
humans.
Fourth,
controlled human exposures PBPK model wouid be
severely
limited.
This
relevant therefore,
any
attempts
to
validate
a
mechanisms have not been
complicated by the fact that elimination
Is further completely
elucidated
In
rats
and
humans.
These
considerations and gaps In it impractical to
the
of
species-specific
elimination of PFOA make generic kinetic model
to
predict
PFOA
understanding
construct
and
apply
a
human PBPK or following Ingestlon
or
Inhalation
of PFOA.
The
basis
for
ccoonnscternutcrtaitnigonasnIdn vpallaisdmataing a human PBPK model for PFOA was described and
evaluated.
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