Document ID: EPA-HQ-OPP-2004-0005-0012
Agency: epa
Document Type: Supporting & Related Material
Title: 
Posted Date: 2004-03-08T05:00Z

Appendix
D,
Page
1
of
15
Appendix
D.
Avian
Respiratory
Physiology
Project
Introduction
This
work
plan
originally
included
two
primary
purposes:
determination
of
maximum
respirable
and
inhalable
particle
size,
and
a
comparison
of
avian
and
mammalian
respiratory
physiology.
Determining
the
maximum
respirable
particle
size
would
allow
prediction
of
inhalation
dose
for
avian
species,
while
a
comparison
of
avian
and
mammalian
respiratory
physiology
will
aid
in
determining
potential
causes
for
relative
chemical
absorption
differences
between
birds
and
mammals.
While
plenty
of
data
exist
for
mammalian
inhalation
and
avian
ingestion
toxicity,
little
to
none
exist
for
avian
inhalation.
It
is
hoped
that
information
resulting
from
this
investigation
will
aid
in
predicting
avian
inhalation
toxicity
from
avian
oral
toxicity.

Very
little
information
was
found
regarding
respirable
or
inhalable
particles
size
for
avian
species.
Only
one
study
was
found
that
related
particulate
deposition
in
the
respiratory
tract
to
particulate
size.
This
was
with
one
species,
the
domestic
chicken.
The
largest
particle
diameter
that
was
shown
to
have
been
deposited
into
the
lung
was
in
the
range
of
3.7
to
7

m.
Other
studies
were
found,
but
they
did
not
have
a
wide
particulate
size
range,
being
restricted
to
around
1

m.

Some
excellent
papers
were
found
describing
and
discussing
avian
respiratory
anatomy
and
physiology.
A
couple
of
papers
compared
mammalian
and
avian
respiratory
anatomy
and
physiology,
being
appropriate
for
our
purposes.
Three
important
differences
were
evident.
First,
the
gaseous
exchange
tissue
in
avian
lungs
is
thinner
than
the
analogous
tissue
in
mammalian
lungs.
Second,
the
surface
area
of
such
exchange
tissue
in
a
bird
is
greater
than
in
a
similar
sized
mammal.
Third,
the
avian
lung
more
efficiently
exchanges
gases
with
inspired
air
by
both
crossand
counter­
current
mechanisms,
a
method
quite
different
from
that
utilized
in
mammalian
lungs.
The
first
two
aspects
are
applicable
for
consideration
of
chemical
absorption
from
both
particulate
and
gaseous
phases.
The
last
aspect
would
be
most
applicable
for
gaseous
phase
chemicals.
This
information
indicates
that
chemical
absorption
through
respiratory
surfaces
is
likely
quite
different
between
mammals
and
birds.
It
is
therefore
predicted
that
toxicological
response
in
birds,
via
inhalation,
will
be
greater
for
birds
compared
to
mammals
due
to
increased
chemical
absorption
in
avian
lungs.
The
question
is,
how
much
greater?

Maximum
Inhalable
and
Respirable
Particle
Size
Two
studies
investigating
particulate
deposition
in
avian
lungs
were
found.
The
white
leghorn
chicken
(
Gallus
domesticus)
was
the
species
utilized
in
both
studies.
In
the
earlier
study,
five
discrete
radio­
labeled
particle
sizes
(
0.091,
0.176,
0.312,
1.1,
and
3.7­
7.0

m)
were
inhaled
through
a
mask
by
anaesthetized
chickens
(
Hayter
and
Besch,
1974).
Different
sections
of
the
hen
were
then
assayed
for
radioactivity
as
an
indication
of
particulate
deposition.
The
sections
were
divided
into
the
head,
trachea,
lung
region,
and
posterior
air
sac
(
deepest
penetration).
While
all
particles
penetrated
into
the
deepest
portions
of
the
lung,
particle
size
and
penetration
Appendix
D,
Page
2
of
15
depth
into
the
respiratory
tract
were
inversely
related
for
particle
sizes
up
to
0.312

m
(
Figure
1).
While
the
3.7
to
7

m
particles
did
not
appear
to
follow
the
same
trend,
the
data
for
all
particles
in
that
range
were
lumped
together
such
that
the
sum
of
the
radioactivity
for
all
particle
sizes
within
that
range
exceeded
the
radioactivity
for
a
single
particle
size.
What
was
evident
was
the
largest
proportion
of
the
large
particles
were
deposited
in
the
head
region,
while
the
largest
proportion
of
the
small
particles
were
deposited
in
the
posterior
air
sac
and
lung
regions.
This
indicates
that
increasingly
large
particles
have
a
decreasing
likelihood
of
penetration
into
the
lungs.

A
second
study
also
utilized
chickens
to
investigate
particulate
deposition
within
avian
lungs
(
Mensah
and
Brain,
1982).
However,
they
restricted
the
range
of
particle
sizes
to
0.45

m
(
±
1.4),
meaning
the
largest
particle
size
was
in
the
neighborhood
of
2

m.
Considering
that
the
previous
study
had
shown
larger
particle
sizes
were
indeed
respirable,
the
Mensah
and
Brain
study
can
not
be
used
to
assess
maximum
respirable
particle
size.
While
they
criticized
the
particle
size
specific
deposition
pattern
found
by
Hayter
and
Besch,
and
found
no
statistically
significant
deposition
pattern
in
their
own
study;
visual
inspection
revealed
that
the
majority
of
deposition
was
in
the
lungs
and
posterior
air
sacs.
This
is
similar
to
what
Hayter
and
Besch
found
for
similarly
sized
particles
in
their
study.

What
neither
of
these
studies
allow
is
determination
of
maximum
respirable
or
inhalable
particle
sizes.
Respirable
particles
are
those
that
enter
the
lung,
while
inhalable
particles
are
those
that
pass
through
the
nares
and
enter
the
upper
respiratory
tract,
but
do
not
enter
the
lungs
or
air
sacs.
In
both
studies,
all
particles
penetrated
to
the
most
posterior
portions
of
the
respiratory
tract,
regardless
of
size.
What
was
evident
was
that
penetration
into
the
respiratory
tract
was
inversely
related
to
particle
size.

An
investigation
of
studies
on
particulate
deposition
in
mammalian
respiratory
systems
was
conducted
to
see
if
information
from
those
studies
could
be
used
to
determine
a
maximum
respirable
particle
size
for
avian
species.
An
understanding
of
factors
that
govern
particulate
deposition
would
be
necessary
to
determine
the
accuracy
of
such
an
extrapolation.

Three
major
modes
of
particulate
deposition
occur
within
airways;
inertial
impaction,
sedimentation,
and
Brownian
motion
(
Brown
et
al.,
1997,
Heyder
et
al.,
1986,
Eisenbud,
1952).
Inertial
impaction
is
the
important
deposition
mode
in
the
upper
respiratory
tract
and
nasal
passages.
Air
flow
velocity
and
turbulence
in
this
region
impart
enough
inertia
upon
particles
that
they
will
overcome
gaseous
forces
and
collide
with
respiratory
surfaces.
The
inertia
that
a
particle
attains
is
proportional
to
particle
density
and
diameter,
and
air
velocity.
The
greater
the
particle
density
and
air
flow,
the
greater
the
inertia,
and
the
more
likely
there
will
be
impaction.
Once
the
air
velocity
decreases
beyond
a
certain
point,
particles
not
subject
to
inertial
impaction
are
deposited
by
sedimentation.
This
tends
to
be
the
case
deeper
within
the
respiratory
pathways
where,
at
least
for
mammals,
air
velocity
is
less
than
in
the
nasal
region.
Brownian
motion
is
the
mode
of
deposition
for
particles
with
a
diameter
of
generally
less
than
0.1
µ
m
(
Eisenbud,
1952).
Brownian
motion
describes
the
random
motion
of
very
small
gaseous
particles
whose
direction
Appendix
D,
Page
3
of
15
can
be
altered
through
collision
with
other
gaseous
molecules.
The
important
point
to
understand
is
that
these
factors
will
be
the
same
regardless
of
the
species.

A
species­
specific
factor
that
could
alter
particulate
deposition
is
respiratory
system
morphology
(
Heyder
et
al.,
1986).
Particulate
deposition
within
lungs
of
organisms
with
significantly
different
respiratory
morphologies
is
likely
to
differ
between
those
organisms,
as
the
differing
morphologies
will
affect
air
velocity
and
turbulence.
With
this
in
mind,
and
since
there
is
a
paucity
of
particulate
deposition
information
for
avian
species,
are
mammalian
and
avian
lung
morphologies
similar
enough
such
that
data
from
studies
on
particulate
deposition
in
mammalian
respiratory
systems
may
be
extrapolated
to
avian
respiratory
systems?

As
might
be
expected,
the
avian
and
mammalian
respiratory
systems
have
similarities
and
differences.
The
respiratory
systems
for
both
are
similar
cranial
to
the
first
bifurcation
(
Brown
et
al.,
1997),
but
not
identical.
Both
have
a
nasal
cavity
with
communicating
sinuses,
a
cartilaginous
supported
larynx,
and
a
tracheal
lumen.
In
this
region,
one
difference
is
the
tracheal
lumen
in
mammals
has
a
U­
shaped
cartilaginous
support
while
the
avian
lung
has
a
circular
cartilaginous
support.
The
fact
that
the
cartilage
does
not
completely
enclose
the
trachea
means
that
there
is
a
portion
of
it
that
is
collapsible.
The
collapsible
tissue
in
the
mammalian
lung
is
purported
to
allow
the
coughing
reflex
in
mammals
to
clear
the
trachea.
It
could
also
lead
to
greater
turbulence
in
mammalian
trachea
as
compared
to
the
avian
trachea,
thereby
leading
to
greater
inertial
impaction
as
compared
to
avian
species.
Differences
in
the
nasal
cavity
may
also
exist.
The
avian
nasal
cavity
is
lined
with
semi­
circular
conchae,
whereas
the
mammalian
cavity
is
not.
Both
structures
generate
considerable
turbulence
that
would
lead
to
particulate
impaction.
But
it
is
unclear
if
the
structural
differences
in
the
upper
respiratory
tract
are
great
enough
to
lead
to
significantly
different
particulate
deposition
characteristics
in
this
region.

Considerable
differences
exist
between
the
mammalian
and
avian
lung.
The
avian
lung
consists
of
a
set
of
air
sacs
that
act
like
bellows
circulating
air
uni­
directionally
through
the
lung
(
Brown
et
al..
1997,
Maina
et
al.,
1989).
The
mammalian
lung
is
a
series
of
bifurcating
airways
in
which
air
flow
is
bi­
directional.
The
gas
exchange
tissues
in
avian
lungs
line
a
series
of
parallel
structures
through
which
the
air
flows
while
the
analogous
tissue
in
mammals
lines
many
small
sacs
called
alveoli.
These
structural
differences
indicate
that
particulate
deposition
characteristics
within
the
lung
itself
might
be
considerably
different
between
mammals
and
birds.

Following
a
review
of
avian
and
mammalian
morphology,
the
upper
respiratory
system
might
be
similar
enough
between
the
two
that
it
might
be
possible
to
determine
a
maximum
respirable
particle
size
for
avian
species
based
on
particulate
deposition
studies
with
mammals.
It
is
still
not
possible
to
predict
maximum
inhalable
particle
size.

One
study
proposing
modeling
of
interspecies
inhaled
particulate
deposition
in
mammals
might
be
particularly
useful
to
determine
whether
or
not
maximum
respirable
particle
size
in
rats
and
humans
would
be
similar
to
that
for
birds.
A
plot
of
the
fraction
of
particles
entering
the
trachea
that
are
deposited
in
the
naso­
pharyngeal
and
tracheal
region
relative
to
particle
size
Appendix
D,
Page
4
of
15
(
maximum
particle
size
in
studies
was
6

m)
revealed
an
asymptotic
relationship
in
humans
at
maximal
activity
was
being
approached
for
6

m
particles
(
minute
volume
of
122,000
ml/
min)
(
Figure
2)
(
Martonen
et
al.,
1992).
The
maximum
respirable
particle
size
in
humans
at
maximal
activity
levels
is
likely
to
be
to
close
to
6

m.
As
activity
level
decreased,
no
asymptote
was
evident
for
the
same
particle
size.
This
indicates
that
the
maximum
respirable
particle
size
decreases
as
activity
level,
and
thereby
respiratory
rate
and
minute
volume,
increases.
Similar
plots
for
rats
did
not
reveal
any
asymptotic
relationship
for
6

m
particles
despite
increasingly
elevated
respiratory
activity
(
504
ml/
min)
(
Figure
3),
indicating
that
the
maximum
respirable
particle
size
is
likely
greater
for
rats
than
for
humans.
This
is
ironic
considering
that
the
nares
diameter
in
humans,
being
much
greater
than
that
for
rats,
should
allow
larger
particles
to
pass
compared
to
rats.
What
might
be
responsible
for
the
difference
in
particulate
deposition?

Interestingly,
two
factors
pertaining
to
inertial
impaction
might
explain
these
differences.
Upper
respiratory
tract
form
in
humans
is
different
relative
to
rats.
It
makes
an
approximately
90
degree
turn
from
horizontal
to
vertical
in
humans,
while
it
remains
essentially
horizontal
in
rats.
Any
inertial
forces
attained
by
particles
are
more
likely
to
lead
to
impaction
when
the
particle
encounters
a
90
degree
turn
such
as
in
the
upper
respiratory
tract
of
an
organism
like
a
human
or
bird.
In
addition,
the
minute
volume
in
humans
was
much
greater
than
it
was
for
rats.
Minute
volume
for
the
humans
in
the
study
ranged
from
7,000
to
122,000
ml/
min,
and
from
170
to
504
ml/
min
for
rats.
These
great
differences
could
lead
to
considerable
differences
in
particulate
inertia
for
identically
sized
particles,
and
lead
to
different
impaction
likelihood.
It
is
apparent
from
this
study
that
despite
the
similarity
in
respiratory
system
structure
between
rats
and
humans,
factors
such
as
form
and
minute
volume
appear
to
have
a
considerable
effect
on
particulate
deposition,
and
thereby
maximum
respirable
particle
size.

Based
on
minute
volume
alone,
it
might
be
expected
that
the
data
for
rats
might
be
useable
for
prediction
of
maximum
respirable
particle
size
for
birds.
Using
the
allometric
relationship
between
body
weight
and
inhalation
rate
(
ml/
min)
cited
in
the
wildlife
exposures
handbook
(
USEPA,
1993),
the
minute
volume
for
non­
passerine
birds
up
to
1
kg
body
weight
will
be
around
300
ml/
min.
This
is
within
the
reported
minute
volume
range
for
the
rats
in
the
Martonen
et
al.
study.
However,
the
form
of
the
upper
respiratory
tract
differs
considerably
between
the
rat
and
birds.
As
noted
earlier,
this
could
have
a
significant
affect
upon
particulate
deposition
within
the
upper
respiratory
tract
meaning
that
the
rat
data
may
not
accurately
reflect
what
would
be
expected
for
birds.

On
the
other
hand,
based
on
the
form
of
the
upper
respiratory
tract,
the
data
reported
in
Martonen
et
al.
for
humans
might
reflect
what
would
be
expected
for
birds.
The
upper
respiratory
tract
makes
an
approximate
90
degree
turn
in
both
humans
and
birds.
However,
the
minute
volumes
differ
considerably.
This
would
lead
to
large
inertial
differences
between
the
two
for
the
same
particle
size,
ultimately
leading
to
differences
in
particulate
impaction.
Therefore,
the
human
data
may
not
be
applicable
to
avian
species.

The
data
cited
in
Martonen
et
al.
(
1992)
indicated
an
inverse
relationship
between
Appendix
D,
Page
5
of
15
maximum
respirable
particle
size
and
minute
volume.
Maximum
respirable
particle
size
was
predicted
from
a
plot
of
the
fraction
value
noted
earlier,
yet
log
transformed,
versus
the
particulate
diameter.
Setting
the
fraction
value
to
0.3
(
equivalent
to
the
log
transformed
fraction
deposition
of
one)
in
the
relationship
equation
allowed
calculation
of
an
upper
limit
for
particle
size.
Anything
smaller
would
be
expected
to
pass
through
the
naso­
pharyngeal
region
and
be
considered
respirable,
while
anything
larger
would
not.
The
apparent
asymptotic
relationship
noted
earlier
indicates
that
the
relationship
is
not
necessarily
linear.
Therefore,
a
maximum
value
predicted
in
this
manner
would
likely
underestimate
the
actual
maximum.
However,
using
the
same
method
for
all
data
will
yield
a
constant
underestimation
for
all
data,
and
allow
examination
of
the
relationship
between
minute
volume
and
maximum
respirable
particle
size.

If
the
predicted
maximal
diameters
are
plotted
relative
to
minute
volume,
it
appears
an
inverse
relationship
exists
between
minute
volume
and
maximum
respirable
particle
size
(
Figures
4
and
5).
However,
a
significant
gap
exists
for
minute
volumes
between
7,000
and
504
ml/
min.
In
addition,
the
maximum
respirable
particle
size
will
not
get
infinitely
large
at
infinitely
low
minute
volumes
since
gravitational
forces
will
exceed
the
inertial
forces
up
to
an
unknown
particle
size,
and
some
particles
will
be
so
small
that
they
will
not
impact
despite
tremendous
airflow
velocity.
Therefore,
a
complete
relationship
is
not
evident.

Respiratory
structure,
form,
and
minute
volumes
all
need
to
be
known
for
predictions
of
maximum
respirable
particle
size
to
be
predicted.
For
avian
species,
allometric
relationships
have
been
established
for
minute
volume,
and
upper
respiratory
tract
structure
and
form
is
likely
to
be
similar
among
species.
What
also
needs
to
be
known
is
a
relationship
between
particulate
deposition
in
avian
species
and
the
above
factors.
These
data
do
not
exist
for
avian
species,
leaving
only
mammalian
data
for
any
modeling
effort.
Significant
respiratory
structure
differences
exist
between
mammals
and
birds,
emphasizing
the
difficulty
in
extrapolating
from
the
larger
mammalian
data
base
to
the
virtually
non­
existent
avian
data.

In
conclusion,
very
little
work
has
been
done
to
establish
what
the
maximum
respirable
or
inhalable
particle
size
for
avian
species
would
be.
To
this
point,
the
largest
particle
size
that
has
been
demonstrated
to
be
respirable
in
birds
is
7

m.
While
this
is
certainly
not
likely
to
be
the
maximum,
prediction
of
the
maximum
particle
size
would
undoubtedly
be
complex,
leaving
7

m
as
the
most
accurate
estimate.

Comparison
of
Avian
and
Mammalian
Respiratory
Physiology
This
comparison
of
respiratory
physiology
will
center
on
a
discussion
of
those
aspects
affecting
chemical
uptake
from
inhaled
air
and
pose
how
the
physiological
differences
might
affect
relative
absorption
of
chemicals
from
the
air.

Assuming
the
chemical
has
bypassed
impaction
at
sites
elsewhere
in
the
respiratory
system
and
has
reached
gas
exchange
tissue
sites,
three
primary
factors
govern
chemical
uptake,
the
thickness
of
tissue
through
which
the
chemical
must
pass
(
assuming
a
passive
transport
process)
Appendix
D,
Page
6
of
15
in
order
to
enter
the
blood,
the
surface
area
of
the
exchange
tissue,
and
the
chemical
concentration
gradient
between
that
of
the
inhaled
air
and
that
in
the
blood.
By
Fick's
law
of
diffusion:

 
  
 
Q
D
A
u
x
t
=
 
×
×
×
(
)
where,


Q
=
mass
uptake
D
=
chemical
specific
diffusion
constant
A
=
surface
area
of
the
diffusion
site

u
=
concentration
gradient

x
=
tissue
thickness

t
=
duration
of
diffusion
The
rate
of
diffusion
and,
therefore,
the
total
chemical
uptake
per
unit
time,
is
inversely
related
to
the
distance
the
chemical
must
travel
(
gas
exchange
tissue
thickness
for
our
purposes)
and
directly
proportional
to
both
the
surface
area
of
the
exchange
tissue
and
concentration
gradient.
These
were
the
primary
areas
of
comparison
in
this
discussion.

The
gas
exchange
tissue
surface
area
in
an
avian
lung
is
greater
than
that
in
the
lung
of
a
mammal
of
the
same
mass
(
Maina
et
al.,
1989).
A
log­
log
plot
between
body
mass
and
gas
exchange
tissue
surface
area
revealed
the
relationships
between
body
weight
and
exchange
tissue
surface
area
for
mammals
and
birds
are
parallel
(
from
2
to
1,300
g
bw)
with
the
y­
intercept
for
birds
(
60.1)
being
approximately
14%
greater
than
for
mammals
(
52.1).
In
addition,
the
mass
specific
surface
area
of
the
gas
exchange
tissue
(
cm2
per
gram
body
weight)
in
both
mammals
and
birds
is
inversely
related
to
body
mass.
Therefore,
assuming
an
even
distribution
of
chemical
across
the
entire
surface
area
of
the
exchange
tissue,
the
contribution
of
gas
exchange
tissue
surface
area
to
chemical
uptake
should
be
approximately
14%
greater
in
a
bird
than
in
a
mammal
of
the
same
body
mass
with
the
same
inhalation
rate.

Not
only
is
the
surface
area
of
the
exchange
tissue
greater
in
avian
lungs,
but
the
thickness
of
the
exchange
tissue
in
avian
lungs
is
less
than
that
of
the
analogous
tissue
in
a
similar
sized
mammal
(
Maina
et
al.,
1989).
A
log­
log
plot
between
body
mass
and
the
thickness
of
the
gas
exchange
tissue
revealed
that
the
exchange
tissue
thickness
in
bird
lungs
is
approximately
twice
that
for
the
analogous
tissue
in
a
mammal
of
the
same
mass;
the
y­
intercept
for
the
relationships
were
116.5
for
birds
and
238
for
mammals.
In
addition,
the
relationships
are
not
parallel,
with
the
slope
for
mammals
being
approximately
double
that
for
birds,
indicating
that
the
thickness
difference
increases
as
body
mass
increases.
As
a
result,
the
contribution
of
exchange
tissue
thickness
to
chemical
absorption
in
a
bird
should
be
at
least
twice
what
would
be
expected
in
mammal
of
the
same
body
mass.

The
previous
two
aspects
of
avian
lung
morphology
address
two
aspects
of
Fick's
law
of
diffusion;
surface
area
of
the
diffusion
site
and
tissue
thickness.
The
affect
of
these
two
aspects
on
diffusion
was
already
mentioned.
For
the
purposes
of
our
discussion
here,
the
chemical
Appendix
D,
Page
7
of
15
specific
diffusion
rate
and
the
duration
of
diffusion
are
assumed
to
be
constant
for
comparative
purposes.
The
only
remaining
contributing
factor
in
Fick's
law
is
the
concentration
gradient.

Passive
diffusion
occurs
whenever
there
is
a
concentration
difference
between
two
compartments.
The
greater
the
concentration
difference,
the
greater
is
the
"
force"
driving
a
chemical
molecule
to
move
from
the
higher
concentration
area
to
the
lower
concentration
area.
In
addition,
the
longer
that
concentration
difference
is
maintained,
the
longer
the
"
force"
will
be
maintained.
While
the
concentration
difference
between
the
inhaled
air
and
blood
may
not
initially
be
any
greater
in
birds
than
in
mammals,
birds
are
able
to
maintain
that
difference
for
a
greater
period
of
time,
enhancing
the
diffusion
of
chemical
from
the
inhaled
air
into
the
blood.

The
cross­
current
gas
exchange
mechanism
in
birds
is
a
more
efficient
method
of
gaseous
chemical
absorption
than
the
alveolar
gas
exchange
mechanism
in
mammals
(
Scheid,
1979).
In
the
cross­
current
mechanism,
venous
blood
flow
in
one
direction
from
a
single
vein
divides
into
multiple
venules
that
cross
an
air
capillary
containing
air
traveling
perpendicular
to
the
blood
flow.
In
such
an
arrangement,
chemical
concentrations
in
the
air
will
always
be
greater
than
the
chemical
concentration
in
the
blood
of
adjacent
venules,
thereby
maintaining
the
concentration
gradient
and
maintaining
the
diffusion
rate.
The
concentrations
in
the
blood
and
air
will
not
reach
an
equilibrium.
In
alveolar
gas
exchange,
venous
blood
flows
through
a
capillary
network
around
an
alveolus
containing
essentially
stagnant
air.
Chemical
concentrations
in
the
surrounding
capillaries
will
begin
to
approach
those
in
the
air
over
time,
decreasing
the
concentration
gradient
and
slowing
the
diffusion
rate.
Therefore,
while
the
chemical
concentration
gradient
between
blood
and
gas
in
both
birds
and
mammals
might
initially
be
the
same,
over
time
it
will
decrease
in
the
mammalian
lung
yet
remain
relatively
constant
in
the
avian
lung.
This
enhances
gaseous
chemical
uptake
in
the
avian
lung
relative
to
the
mammalian
lung.

The
cross­
current
mechanism
explains
uptake
of
chemicals
that
are
either
gaseous
or
dissolved
in
a
liquid.
What
is
unknown
is
if
the
efficiency
of
the
cross­
current
exchange
mechanism
applies
to
particulate­
bound
chemicals.
Both
exchange
tissue
thickness
and
surface
area
are
applicable
to
chemical
containing
particulates
that
may
be
deposited
onto
the
exchange
tissue.
Therefore,
those
are
the
only
two
aspects
that
will
be
further
considered.

Having
established
that
the
thickness
and
surface
area
of
the
exchange
tissue
in
avian
lungs
favors
enhanced
chemical
uptake
in
avian
lungs
relative
to
mammalian
lungs,
there
remains
a
question
concerning
potential
differences
in
chemical
absorption
in
avian
and
mammalian
lungs.

Two
allometric
relationships
reported
in
Maina
et
al.
(
1989)
along
with
Fick's
law
of
diffusion
were
utilized
to
determine
approximately
how
much
different
chemical
uptake
via
inhalation
will
be
for
avian
and
mammalian
lungs.
Both
of
the
reported
relationships
were
mentioned
earlier;
one
for
exchange
tissue
thickness
and
the
other
for
exchange
tissue
surface
area.
Both
were
utilized
to
calculate
tissue
thicknesses
and
surface
areas
for
both
mammalian
and
avian
lungs,
and
are
reported
in
Table
1.
It
can
be
seen
that
the
difference
between
exchange
tissue
surface
areas
in
mammalian
and
avian
lungs
remains
constant
over
a
body
mass
range
of
1
Appendix
D,
Page
8
of
15
to
2,000
g.
This
indicates
that
the
allometric
relationships
for
surface
area
in
mammals
and
birds
are
parallel.
On
the
other
hand,
exchange
tissue
thickness
increases
more
rapidly
with
body
weight
in
mammals
as
compared
to
birds
indicating
the
influence
of
tissue
thickness
on
chemical
diffusion
will
not
be
constant
for
all
body
weights.
Diffusion
will
decrease
as
body
weight
increases
due
to
increased
tissue
thickness,
but
for
mammals
it
will
decrease
more
per
unit
body
weight
change
as
compared
to
birds.
This
means
the
ratio
of
chemical
mass
absorption
in
birds
relative
to
mammals
will
likely
increase,
from
2.4
to
3.5,
as
the
respective
body
mass
increases,
favoring
absorption
in
birds
(
Table
1).
Appendix
D,
Page
9
of
15
0
5
10
15
20
25
30
35
40
45
expired
head
trachea
lung
region
posterior
air
sac
%

of
total
radioactivity
within
size
class
0.091
0.176
0.312
1.1
3.7
­
7
Figure
1.
Deposition
patterns
for
particulates
in
the
respiratory
system
of
white
leghorn
chickens
(
Gallus
domesticus).
Data
from
Hayter
and
Besch,
1974.
Appendix
D,
Page
10
of
15
Tracheo­
bronchial
particulate
deposition
in
humans
0.00
0.05
0.10
0.15
0.20
0.25
0.30
0.35
0
1
2
3
4
5
6
7
Particulate
diame
ter
(
um)

Proportion
of
inhaled
particles
deposited
(

log
proportion)
sedentary
low
activity
light
activity
heavy
activity
maximal
activity
Figure
2.
Particulate
deposition
tracheo­
bronchial
region
of
the
human
respiratory
tract
under
varying
degrees
of
activity.
Data
from
Martonen
et
al.,
1992.
Appendix
D,
Page
11
of
15
Particulate
deposition
in
tracheo­
bronchial
region
of
rats
0.00
0.02
0.04
0.06
0.08
0.10
0.12
0.14
0
1
2
3
4
5
6
7
Particulate
diameter
(
um
)

Proportion
of
inhaled
particulates
deposited
(

log
proportion)
0%
CO2
2%
CO2
4%
CO2
6%
CO2
8%
CO2
Figure
3.
Particulate
deposition
in
the
tracheo­
bronchial
region
of
the
rat
respiratory
tract
under
varying
degrees
of
activity.
Data
from
Martonen
et
al.,
1992.
Appendix
D,
Page
12
of
15
Predicted
maximum
respirable
particle
size
0
5
10
15
20
25
30
35
40
0
100
200
300
400
500
600
Minute
volume
Particle
size
(

um)
Predicted
maximum
respirable
particle
size
Figure
4.
Predicted
maximum
respirable
particle
size
relative
to
minute
volume;
rats.
Data
from
Martonen
et
al.,

1992.
Appendix
D,
Page
13
of
15
Maximum
respirable
particle
size
0
2
4
6
8
10
12
0
20000
40000
60000
80000
100000
120000
140000
Minute
volume
Particle
size
Maximum
respirable
particle
size
Figure
5.
Predicted
maximum
respirable
particle
size
relative
to
minute
volume;
humans.
Data
from
Martonen
et
al.,

1992.
Appendix
D,
Page
14
of
15
Table
1.
Relative
diffusion
across
pulmonary
exchange
tissue
for
chemicals
inhaled
by
birds
and
mammals.

Exchange
tissue
surface
area
(
cm2)
a
Exchange
tissue
thickness
(
nm)
b
Relative
diffusion
rate
c
BW
(
g)
avian
mamma
l
avian/
mammal
avian
mamma
l
mammal/
avian
Q
avian
Q
mammal
Qa/
Qm
1
61
52
1.16
117
238
2.0
0.52
0.22
2.4
10
463
398
1.16
129
292
2.3
3.59
1.36
2.6
20
854
734
1.16
133
311
2.3
6.42
2.36
2.7
30
1221
1050
1.16
135
323
2.4
9.02
3.25
2.8
40
1574
1353
1.16
137
331
2.4
11.49
4.09
2.8
50
1917
1648
1.16
138
338
2.4
13.85
4.88
2.8
60
2252
1936
1.16
140
344
2.5
16.14
5.64
2.9
70
2580
2218
1.16
140
348
2.5
18.37
6.37
2.9
80
2903
2496
1.16
141
353
2.5
20.55
7.08
2.9
90
3222
2770
1.16
142
356
2.5
22.68
7.77
2.9
100
3536
3040
1.16
143
360
2.5
24.78
8.45
2.9
110
3846
3307
1.16
143
363
2.5
26.84
9.11
2.9
120
4153
3571
1.16
144
366
2.5
28.88
9.77
3.0
130
4457
3832
1.16
144
368
2.6
30.88
10.40
3.0
140
4759
4091
1.16
145
371
2.6
32.86
11.03
3.0
150
5058
4348
1.16
145
373
2.6
34.82
11.66
3.0
160
5354
4603
1.16
146
375
2.6
36.76
12.27
3.0
170
5649
4857
1.16
146
377
2.6
38.68
12.87
3.0
180
5941
5108
1.16
146
379
2.6
40.58
13.47
3.0
190
6232
5358
1.16
147
381
2.6
42.46
14.06
3.0
200
6521
5606
1.16
147
383
2.6
44.33
14.64
3.0
210
6808
5853
1.16
147
385
2.6
46.18
15.22
3.0
220
7093
6098
1.16
148
386
2.6
48.02
15.79
3.0
1000
27007
23219
1.16
158
443
2.8
171.04
52.47
3.3
2000
49806
42820
1.16
163
471
2.9
305.97
90.91
3.4
(
a)
Surface
area
=
60.6*
BW0.883
(
birds)
§
;
=
52.1*
BW0.883
(
mammals)
§
(
b)
Mean
harmonic
thickness
=
116.51*
BW0.044
(
birds)
§
;
=
237.66*
BW0.090
(
mammals)
§
(
c)
Q
=
surface
area
/
thickness.
From
Fick's
law
assuming
constant
chemical
specific
diffusion
coefficient,
concentration
gradient,
and
exposure
period.
Q
and
diffusion
are
directly
proportional.
§
Allometric
equations
from
Maina
et
al.
(
1989).
Appendix
D,
Page
15
of
15
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