OVERVIEW
OF
ASULAM
RISK
ASSESSMENT
Introduction
August
2,
2002
The
Agency
has
completed
its
review
and
announces
the
tolerance
reassessment
decision
for
asulam.
This
decision
also
releases
to
the
public
the
human
health
assessment,
as
presented
fully
in
the
document
entitled
 
Asulam:
HED
Human
Health
Assessment
for
the
Tolerance
Reassessment
Eligibility
Decision
(
TRED) 
dated
February
28,
2002,
and
related
documents
supporting
this
decision.
The
purpose
of
this
overview
is
to
assist
the
reader
by
identifying
the
key
features
and
findings
of
this
risk
reassessment
in
order
to
better
understand
the
conclusions
reached
in
the
tolerance
reassessment.
This
overview
was
developed
in
response
to
comments
and
requests
from
the
public,
which
indicated
that
the
risk
assessments
(
and
other
like
documents)
were
difficult
to
understand,
that
they
were
too
lengthy,
and
that
it
was
not
easy
to
compare
the
assessments
for
different
chemicals
due
to
the
use
of
different
formats.

FFDCA
requires
the
Agency
to
review
all
the
tolerances
for
registered
chemicals
in
effect
on
or
before
the
date
of
the
enactment
of
FQPA.
In
reviewing
these
tolerances,
the
Agency
must
consider,
among
other
things,
aggregate
risks
from
non­
occupational
sources
of
pesticide
exposure,
whether
there
is
increased
susceptibility
to
infants
and
children,
and
the
cumulative
effects
of
pesticides
with
a
common
mechanism
of
toxicity.
The
tolerances
are
considered
reassessed
once
the
safety
finding
has
been
made
or
a
tolerance
revocation
occurs.
A
reregistration
eligibility
decision
(
RED)
for
asulam
was
completed
in
September
1995,
prior
to
FQPA
enactment;
therefore
it
needed
to
be
updated
to
consider
the
provisions
of
the
Act.

FQPA
requires
that
the
Agency,
when
considering
whether
to
establish,
modify,
or
revoke
a
tolerance,
consider
 
available
information 
concerning
the
cumulative
effects
of
the
particular
pesticide s
residues
and
 
other
substances
that
have
a
common
mechanism
of
toxicity. 
The
Agency
does
not,
at
this
time,
have
sufficient
reliable
information
available
to
determine
whether
asulam
has
a
common
mechanism
of
toxicity
with
other
substances.
Therefore,
for
the
purposes
of
this
risk
assessment,
the
Agency
has
not
assumed
that
asulam
has
a
common
mechanism
of
toxicity
with
other
substances.
If
EPA
identifies
other
substances
that
share
a
common
mechanism
of
toxicity
with
asulam,
a
cumulative
risk
assessment
for
those
substances
will
be
performed.

The
risk
assessment
and
documents
pertaining
to
the
Agency s
report
on
FQPA
tolerance
reassessment
progress
and
decision
for
asulam
are
available
on
the
Internet
at
http://
www.
epa.
gov/
pesticides/
reregistration/
status.
htm
and
in
the
public
docket.
Because
the
risks
posed
by
the
use
of
asulam
are
low
and
not
of
concern
to
the
Agency,
the
normal
process
of
meeting
stakeholders
(
i.
e.,
growers,
extension
offices,
environmental
and
commodity
groups,
and
other
government
offices)
to
discuss
risks
of
concern
and
solicit
input
on
risk
mitigation
strategies
was
not
necessary
for
this
chemical.
Rather,
the
Agency s
report
on
FQPA
tolerance
reassessment
progress
and
interim
risk
management
decision
for
asulam
will
be
announced
in
the
Federal
Register.
Since
there
are
no
risk
concerns
for
asulam
alone,
no
further
actions
are
warranted
at
this
time
pending
a
determination
of
whether
a
cumulative
risk
assessment
for
asulam
may
be
needed
and
is
completed.

Risks
summarized
in
this
document
are
those
that
result
only
from
the
use
of
asulam.
The
Food
Quality
Protection
Act
(
FQPA)
requires
that
the
Agency
consider
 
available
information 
concerning
the
cumulative
effects
of
a
particular
pesticide s
residues
and
 
other
substances
that
have
a
common
mechanism
of
toxicity. 
Since
it
is
possible
that
this
chemical
and
other
substances
could
share
a
common
mechanism
of
toxicological
action,
adverse
health
effects
and
cumulative
low­
level
exposures,
this
review
needs
to
consider
this
potential
interaction..
The
Agency
did
not
perform
a
cumulative
risk
assessment
as
part
of
this
tolerance
reassessment
of
asulam
because
the
Agency
has
not
yet
initiated
a
review
to
determine
if
there
are
any
other
chemical
substances
that
have
a
mechanism
of
toxicity
common
with
that
of
asulam.
If
the
Agency
identifies
other
substances
that
share
a
common
mechanism
of
toxicity
with
asulam,
then
a
cumulative
risk
assessment
will
be
conducted
that
includes
asulam
once
the
final
framework
the
Agency
will
use
for
conducting
cumulative
risk
assessments
is
available.
Asulam s
potential
contribution
to
cumulative
risk
be
reevaluated
at
that
time
and
additional
studies
may
be
required.

Use
Profile
Herbicide:
Asulam
(
methyl
sulfanilylcarbamate)
is
a
selective
postemergent
systemic
carbamate
herbicide
registered
for
sugarcane,
Christmas
tree
plantations,
ornamentals,
turf
(
use
for
sod
farms
only)
and
non­
cropland
uses
(
boundary
fences,
fencerows,
hedgerows,
lumberyards,
storage
areas
and
industrial
facilities,
and
warehouse
lots).
There
are
no
residential
uses
for
asulam
products.

Targeted
Weeds:
western
brackenfern,
marestail,
horseweed,
alexandergrass,
barnyardgrass,
broadleaf
panicum,
bullgrass,
crabgrass,
foxtail,
goosegrass,
itchgrass,
johnsongrass,
paragrass,
and
sandbur.

Formulations:
The
only
end­
use
formulation
of
asulam
is
the
sodium
salt
of
asulam
(
sodium
salt
of
methyl
sulfanilylcarbamate)
which
is
formulated
as
soluble
concentrate/
liquid
(
36.2%
a.
i.).

Methods
of
Application:
Apply
to
sugarcane
as
broadcast,
band,
or
spot
treatment
with
ground
equipment
or
broadcast
by
air
at
3.34
pounds
active
ingredient/
acre
(
lb
ai/
A).
Apply
to
Christmas
trees
as
a
delayed
dormant
spray
with
air
or
ground
equipment
at
3.34
lb
ai/
A.
Apply
to
ornamental
and/
or
shade
trees
or
ornamental
woody
shrubs
and
vines
as
a
postemergence
ground
broadcast
at
3.34
lb
ai/
A.
Apply
to
ornamental
lawns
and
turf
as
a
postemergence
spray
with
ground
equipment
at
2.088
lb
ai/
A.
Apply
to
industrial
areas
(
outdoor),
nonagricultural
rights­
of­
way/
fencerows,
or
nonagricultural
uncultivated
areas
when
needed
as
spray
with
ground
equipment
at
3.34
lb
ai/
A.

2
Use
Summary:
Based
on
pesticide
usage
information
mainly
for
1992
through
2000
for
agriculture
and
1994
through
1999
for
non­
agriculture,
total
annual
domestic
usage
of
sodium
asulam
is
approximately
1.3
million
pounds
active
ingredient
allocated
by
site
mainly
to
sugarcane
(
95%),
lawn
care
operators
and
sod
farms
(
2%
each)
and
institutional
turf
(
1%).
The
average
percent
crop
treated
for
sugarcane,
the
only
registered
agricultural
crop,
is
about
42%,
while
its
average
use
rate
per
acre
is
2.5
pounds
a.
i.
per
application
and
3.0
pounds
a.
i.
per
year.
Generally,
asulam
is
applied
once
per
season
with
a
follow­
up
spot
application
to
clean
up
field
ends.
States
with
the
most
usage
are
Florida,
Louisiana,
and
Texas.

Registrant:
Aventis
CropScience
Classification:
General
Use
Table
1.
Asulam
Usage
Crop
Acres
Grown
(
000)
Acres
Treated
(
000)

Avg
Max
Sugarcane
939
398
498
Lawn
Care
Operators1
­­­

Sod
Farms
­­­

Institutional
Turf2
­­

Ornamentals
­­­

Golf
Courses
­­­

TOTALS
­­­
­

COLUMN
HEADINGS
%
Crop
Treated
Lbs
A.
I.
Applied
(
000)
States
of
Most
Usage
(%
of
lbs
a.
i.
Used)
Avg
Max
Avg
Max
42%

­

­

­

­

­

­
53%
1,211
1,513
FL
LA
TX
(
100%)

­
26
40
FL
100%

­
21
32
FL
(
most)

­
17
25
­

­
3
4
FL
TX
­
2
3
FL
GA
­
1,280
1,600
FL
LA
(
97%)

Avg
=
Weighted
average
in
which
the
most
recent
years
and
more
reliable
data
are
weighted
more
heavily.
Max
=
Estimated
maximum,
which
is
estimated
from
available
data.
1
Lawn
Care
operators
make
applications
to
commercial,
not
residential,
turf
2
Institutional
turf
consists
of
maintained
turf
of
educational
facilities,
cemeteries,
and
parks.

Human
Health
Risk
Assessment
Hazard
The
acute
toxicity
of
asulam
is
low.
The
acute
oral
LD50
for
asulam
in
rats
exceeded
5000
mg/
kg.
The
acute
inhalation
LC50
was
greater
than
5
mg/
L
in
rats.
The
acute
dermal
LD50
for
asulam
in
rabbits
exceeded
4000
mg/
kg.
Application
of
technical
asulam
to
rabbit
eyes
produced
mild
chemosis,
irritation,
and
redness
which
cleared
by
day
seven
post­
treatment.
Asulam
was
not
an
irritant
in
a
primary
skin
irritation
study
in
rabbits.
It
did
not
cause
dermal
sensitization
in
guinea
pigs.

3
Acute
Dietary
(
Food)
Risk
Acute
dietary
risk
is
estimated
based
on
may
be
eaten
in
one
day.
Acute
dietary
exposure
that
is
less
than
100%
of
the
acute
Population
Adjusted
Dose
(
aPAD)
does
not
exceed
the
Agency s
level
of
concern.
The
aPAD
is
the
reference
dose
(
RfD)
adjusted
for
the
FQPA
Safety
Factor.
The
acute
RfD
is
the
dose
at
which
an
individual
could
be
exposed
in
a
single
day
with
no
adverse
health
effects
expected.

An
acute
dietary
risk
assessment
was
not
conducted
for
asulam
because
no
appropriate
toxicological
endpoint
clearly
attributable
to
a
single
exposure
was
identified.
Therefore,
an
acute
reference
dose
(
aRfD)
was
not
established.

Chronic
Dietary
(
Food)
Risk
Chronic
dietary
risk
is
calculated
by
using
the
average
consumption
values
for
food
and
average
residue
values
on
those
foods
over
a
lifetime
or
the
duration
of
exposure
assessed
(
i.
e.,
1
year
for
infants,
6
years
for
children
ages
1­
6
years
and
37
years
for
females
of
childbearing
age
13­
50
years
old.).
Chronic
dietary
exposure
that
is
less
than
100%
of
the
chronic
Population
Adjusted
Dose
(
cPAD)
does
not
exceed
the
Agency s
level
of
concern.
The
cPAD
is
the
chronic
reference
dose
(
cRfD)
adjusted
for
the
FQPA
Safety
Factor.
The
chronic
RfD
is
the
dose
at
which
an
individual
could
be
exposed
over
the
course
of
a
lifetime
with
no
adverse
health
effects
expected.

The
chronic
dietary
assessment
for
asulam
and
its
degradate
sulfanilamide
was
conducted
using
a
Tier
II
analysis
which
assumes
anticipated
residues
from
field
trial
data
and
includes
percent
crop
treated
estimates.
No
monitoring
data
exist
for
asulam.
The
chronic
dietary
exposure
analysis
is
conducted
using
the
Dietary
Exposure
Evaluation
Model
(
DEEM
 
)
.
A
three­
day
average
of
consumption
for
each
subpopulation
is
combined
with
tolerance
residues
in
commodities
to
determine
average
exposures
in
mg/
kg/
day.

 
The
toxicity
endpoint
for
the
chronic
dietary
was
based
on
hyperplastic
changes
in
the
adrenal
medulla
and
thyroid
follicular
cells
on
males
in
a
rat
study
(
NOAEL=
36
mg/
kg/
day).
The
effects
were
observed
at
180
mg/
kg/
day
(
LOAEL).

 
The
uncertainty
factor
is
1000x;
10x
for
individual
variability
and
10x
for
intraspecies
extrapolation.
An
additional
10x
was
added
due
to
increased
susceptibility
in
offspring/
fetuses
based
on
evidence
of
mean
live
births
per
litter.
The
FQPA
Safety
Factor
was
retained
because
(
i)
there
was
evidence
of
quantitative
susceptibility
in
a
two­
generation
reproduction
study
in
the
rat;
and,
(
ii)
the
Agency
does
not
have
data
that
includes
an
examination
of
the
thyroid
gland;
therefore,
the
Agency
recommended
the
requirement
for
a
comparative
thyroid
rat
assay
in
adults
and
offspring
to
examine
thyroid
weight
and
pathology.

 
A
chronic
Reference
Dose
(
cRfD)
of
0.36
mg/
kg/
day
was
established
based
on
the
NOAEL
of
36
mg/
kg/
day,
and
a
100X
uncertainty
factor
for
interspecies
extrapolation,

4
and
intraspecies
variability.
An
additional
safety
factor
of
10X
was
applied
to
the
cRfD
to
account
for
quantitative
increased
susceptibility
in
offspring/
fetuses
resulting
in
a
chronic
Population
Adjusted
Dose
(
cPAD)
of
0.036
mg/
kg/
day.

 
Chronic
dietary
(
food)
risks
for
asulam
and
its
degradate
are
below
the
Agency s
level
of
concern
for
the
general
U.
S.
population
and
all
population
subgroups
(<
1%
of
the
cPAD).

Table
2.
Summary
of
Toxicity
Endpoints
and
Doses
for
Risk
Assessment
EXPOSURE
SCENARIO
DOSE
(
mg/
kg/
day)
ENDPOINT
STUDY
Acute
Dietary
An
appropriate
endpoint
attributable
to
a
single
dose
was
not
identified.

Acute
RfD
=
not
established
Chronic
Dietary
NOAEL1
=
36
mg/
kg/
day
UF
=
100
FQPA
Safety
Factor
=
10
The
LOAEL2
was
180
mg/
kg/
day
based
on
hyperplastic
changes
in
the
adrenal
medulla
and
in
thyroid
follicular
cells
of
males.
Combined
Chronic
Toxicity/
Oncog
enicity
in
the
rat
Chronic
RfD
=
0.36
mg/
kg/
day
Chronic
PAD
=
0.036
mg/
kg/
day
NOAEL1
=
no
observed
adverse
effect
level.
LOAEL2
=
lowest
observed
adverse
effect
level.

Table
3.
Results
of
Chronic
Dietary
Exposure
Analysis
Population
Subgroup
cPAD
(
mg/
kg/
day)
Exposure
(
mg/
kg/
day)
%
cPAD
U.
S.
Population
(
total)
0.036
0.000157
<
1%

All
Infants
(<
1
year)
0.036
0.000300
<
1%

Children
1­
6
years
0.036
0.000449
1%

Children
7­
12
years
0.036
0.000275
<
1%

Females
13­
50
years
0.036
0.000107
<
1%

Males
13­
19
years
0.036
0.000185
<
1%

Males
20+
years
0.036
0.000105
<
1%

Seniors
55+
years
0.036
0.000087
<
1%

Cancer
Dietary
(
Food)
Risk
EPA
previously
classified
Asulam
as
a
Group
C,
possible
human
carcinogen,
based
on
available
studies
in
rats
and
mice.
Based
on
the
weight­
of­
evidence
of
all
available
data,
a
quantitative
estimation
of
cancer
risk
to
humans
was
not
performed.
A
recent
re­
evaluation
of
the
data
(
including
a
second
mouse
study)
reaffirmed
the
Agency's
previous
conclusion
that
a
quantitative
estimation
of
cancer
risk
to
humans
is
not
appropriate.

5
Drinking
Water
Dietary
Risk
Drinking
water
exposure
to
pesticides
can
occur
through
surface
and/
or
ground
water
contamination.
EPA
considers
acute
(
one
day)
and
chronic
(
lifetime)
drinking
water
risks
and
uses
either
modeling
or
actual
monitoring
data,
if
available,
to
estimate
those
risks.
Modeling
is
carried
out
in
tiers
of
further
refinement,
and
is
designed
to
provide
a
high­
end
estimate
of
exposure.
To
determine
the
maximum
allowable
contribution
from
water
allowed
in
the
diet,
EPA
first
looks
at
how
much
of
the
overall
allowable
risk
is
contributed
by
food
and
then
determines
a
 
Drinking
Water
Level
of
Comparison 
(
DWLOC)
to
ascertain
whether
modeled
or
monitored
Estimated
Environmental
Concentrations
(
EECs)
exceed
this
level.
EECs
that
are
above
the
corresponding
DWLOC
are
of
concern
to
the
Agency.

Based
on
environmental
fate
data,
asulam
is
very
mobile
and
has
a
strong
potential
to
leach
into
ground
water
or
move
offsite
into
surface
water.
Sulfanilamide
is
a
major
soil
and
water
degradate
of
asulam.
Since
there
are
no
residential
uses
associated
with
asulam,
only
dietary
exposure
from
food
is
considered
for
purposes
of
calculating
the
DWLOC.

A
drinking
water
assessment
for
asulam
involved
analysis
of
FIRST
(
Tier
I­
surface
water)
computer
modeling
to
estimate
surface
water
concentrations.
Estimated
drinking
water
concentrations
for
ground
water
are
based
on
a
groundwater
study
that
sampled
potable
wells
in
Florida
and
Louisiana
that
were
located
within
1,000
feet
of
an
asulam
treated
area.
The
monitoring
study
was
compared
to
SCI­
GROW
(
Tier
I­
ground
water)
modeling
which
had
lower
detectable
traces
of
asulam
residues.
This
assessment
includes
concentrations
of
parent
asulam
and
the
degradate
sulfanilamide.

 
For
chronic
risk,
potential
exposure
to
asulam
(
combined
with
sulfanilamide)
from
drinking
water
derived
from
surface
water
results
in
a
chronic
EEC
of
272
ppb,
and
for
groundwater
the
chronic
EEC
is
154
ppb.
Upon
comparison
of
the
chronic
DWLOCs
(
1,254
ppb
for
males;
1,075
ppb
for
females;
and
355
ppb
for
children)
with
the
EECs
for
residues
in
surface
and
groundwater,
all
EECs
are
less
than
the
chronic
DWLOCs
for
all
populations.
Therefore,
the
Agency
is
not
concerned
with
potential
chronic
exposure
to
asulam
through
surface
and
groundwater.

Table
4.
Drinking
Water
DWLOC
and
EEC
Comparisons
Population
Subgroup
EECs
(
ppb)

Chronic
Ground
Water
Surface
Water
Adult
males
1254
154
272Adult
Females
1075
Children
(
1­
6
years)
335
6
Residential
Risk
Potential
residential
exposures
are
not
anticipated
as
a
result
of
applications
of
asulam.
Use
sites
include
Christmas
tree
plantings,
turf
(
for
sod
only),
ornamentals
(
junipers
&
yews
only),
and
non­
cropland
(
e.
g.
rights­
of­
way,
fence
rows,
etc.).
The
amount
of
asulam
used
annually
on
use
sites
other
than
sugarcane
is
approximately
12,000
gallons.
Of
these
use
sites,
no
residential
exposures
would
be
anticipated
from
the
Christmas
tree
plantings
and
non­
cropland
sites.
The
use
on
turf
is
restricted
to
sod
farms,
and
the
application
to
the
sod
is
made
four
to
five
months
prior
to
the
sod
being
pulled
up
and
subsequently
sold.
Therefore,
no
residential
exposures
would
be
anticipated
from
the
turf/
sod
use.
The
registrant
stated
that
use
of
asulam
on
ornamentals
is
very
limited,
since
its
cost
is
high.
Use
of
asulam
on
ornamentals
in
a
residential
setting
would
not
be
expected.

Aggregate
Risk
In
examining
aggregate
exposure,
EPA
takes
into
account
the
available
and
reliable
information
concerning
exposures
from
pesticide
residues
in
food
and
other
exposures
including
drinking
water
and
non­
occupational
exposures,
e.
g.,
exposure
to
pesticides
used
in
and
around
the
home
(
residential).
The
aggregate
risk
assessment
for
asulam
considered
only
chronic
exposures
since
acute
dietary
and
water
exposures
are
not
expected
to
be
toxicologically
significant.
There
are
no
residential
uses
of
asulam.
Therefore,
the
considerations
for
aggregate
exposure
are
those
from
food
and
water.

 
Combining
both
the
chronic
dietary
(
food)
risk
estimates
with
the
surface
and
ground
water
estimated
concentrations
(
drinking
water)
for
asulam,
the
chronic
aggregate
(
food
+
drinking
water)
are
below
EPA
levels
of
concern.
Chronic
dietary
risks
estimates
for
all
populations
are
less
than
100%
of
the
cPAD.
Upon
comparison
of
the
chronic
DWLOCs
with
the
EECs
for
residues
of
asulam
in
surface
and
groundwater,
all
EECs
are
less
than
the
chronic
DWLOCs
for
all
populations.

Occupational
and
Ecological
Risk
Because
asulam
is
under
review
for
tolerance
reassessment
only,
no
occupational
or
ecological
risk
assessment
was
conducted
for
this
TRED.
Occupational
and
ecological
risk
management
decisions
were
made
as
part
of
the
1995
Asulam
RED
and
have
been
implemented.

Tolerance
Reassessment
Summary
Sufficient
data
are
now
available
to
reassess
all
tolerances
associated
with
asulam
use
listed
in
40
CFR
§
180.360.
The
Agency
recommends
that
the
tolerance
expression
be
revised
to
include
all
metabolites
containing
the
sulfanilamide
moiety.
Some
product
chemistry
deficiencies
remain
outstanding,
but
they
do
not
impact
the
tolerance
reassessment
eligibility
decision.
However,
the
registrant
needs
to
resolve
all
outstanding
deficiencies
as
listed
below.

 
The
existing
tolerance
of
0.1
ppm
for
asulam
residues
on
sugar
cane
established
in
40
CFR
§
180.360
has
been
reassessed.
The
Agency
recommends
the
tolerance
be
raised
to
7
1.0
ppm.

 
EPA
recommends
a
tolerance
of
30
ppm
for
asulam
residues
in
molasses
from
sugarcane
be
established
in
40
CFR
§
180.360.

 
Based
on
diets
containing
10%
molasses
in
feed,
EPA
recommends
a
tolerance
of
0.05
ppm
for
asulam
residues
in
milk,
meat,
and
fat
from
cattle,
goats,
hogs,
horses,
and
sheep
be
established
in
40
CFR
§
180.360.

 
Based
on
diets
containing
10%
molasses
in
feed,
EPA
recommends
a
tolerance
of
0.2
ppm
for
asulam
residues
in
meat
byproducts
from
cattle,
goats,
hogs,
horses,
and
sheep
be
established
in
40
CFR
§
180.360.

Table
5.
Tolerance
Reassessment
Summary
Commodity
Current
Tolerance
(
ppm)
Tolerance
Reassessment
(
ppm)
Comment
Tolerances
listed
under
40
CFR
§
180.360
Sugarcane,
cane
0.1
1.0
Tolerances
to
be
Established
Under
40
CFR
§
180.360
Sugarcane,
molasses
­
30
Milk
­
0.05
Cattle,
meat
Cattle,
fat
Goat,
meat
Goat,
fat
Hog,
meat
Hog,
fat
Horse,
meat
Horse,
fat
Sheep,
meat
Sheep,
fat
­.
05
Cattle,
meat
byproducts
Goat,
meat
byproducts
Hog,
meat
byproducts
Horse,
meat
byproducts
Sheep,
meat
byproducts
­.
2
0
0
8
Summary
of
Pending
Data
The
following
deficiencies
were
noted
and
remain
outstanding:

 
GLN
860.1200:
Directions
for
Use
 
GLN
830.6317:
Storage
Stability
 
GLN
830.6320:
Corrosion
Characteristics
 
GLN
870.3200:
21­
day
Dermal
Study
in
Rats
with
examination
of
thyroid
weight
and
pathology
 
No
GLN:
28
­
day
Inhalation
Study
in
Rats
with
examination
of
thyroid
weight
and
pathology.
The
guidelines
for
this
study
are
under
development.

 
No
GLN:
Comparative
thyroid
rat
assay
in
adult
and
offspring.
The
adult
study
should
include
interim
measures
(
e.
g.,
7,14,
and
28
days).
The
thyroid
parameters
selected
for
the
comparative
study
should
be
based
on
Agency
guidelines
(
under
current
development)
for
thyroid
testing.

9
