Document ID: EPA-HQ-OPP-2002-0329-0002
Agency: epa
Document Type: Supporting & Related Material
Title: 
Posted Date: 2002-12-06T05:00Z

UNITED
STATES
ENVIRONMENTAL
PROTECTION
AGENCY
WASHINGTON,
D.
C.
20460
OFFICE
OF
PREVENTION,
PESTICIDES
AND
TOXIC
SUBSTANCES
February
28,
2002
MEMORANDUM
SUBJECT:
Asulam.
HED
Human
Health
Assessment
for
the
Tolerance
Reassessment
Eligibility
Decision
(
TRED).
Chemical
No.
106901/
02.
No
MRID
#.
DP
Barcode
No.
D276505.

FROM:
José
J.
Morales,
Chemist/
Risk
Assessor
John
Liccione,
Toxicologist
Barry
O Keef,
Residential
Exposure
Reregistration
Branch
3
Health
Effects
Division
(
7509C)

THRU:
Catherine
Eiden,
Branch
Senior
Scientist
Reregistration
Branch
3
Health
Effects
Division
(
7509C)

TO:
Demson
Fuller,
Chemical
Review
Manager
Special
Review
and
Reregistration
Division
(
7508C)

This
memorandum
and
attachments
are
the
Health
Effects
Division's
Tolerance
Reassessment
Eligibility
Decision
Document
(
TRED)
for
asulam,
taking
into
consideration
requirements
of
the
1996
Food
Quality
Protection
Act
(
FQPA).
This
assessment
only
discusses
the
human
health
risk
assessment
required
for
reassessment
of
tolerances
and
does
not
include
an
occupational
risk
assessment
required
for
reregistration
of
products.
Cumulative
risk
assessment
considering
risks
from
other
pesticides
which
may
have
a
common
mechanism
of
toxicity
is
also
not
addressed
in
this
document.

Attachments:
Hazard
Identification
Review
Committee
(
HIARC)
report
(
J.
Liccione,
12/
6/
01)
FQPA
Committee
Report
(
C.
Christensen,
2/
5/
02)
Toxicology
Chapter
(
J.
Liccione,
12/
12/
01)
Chemistry
Chapter
(
J.
Morales,
12/
6/
01)
Dietary
Exposure
Analysis
(
J.
Morales,
12/
18/
01)
Drinking
Water
Assessment
to
Support
the
TRED
for
Asulam
(
N.
Birchfield,
1/
8/
02)
ASULAM
HED s
HUMAN
HEALTH
RISK
ASSESSMENT
1.0
Executive
Summary
The
Health
Effects
Division
(
HED)
has
conducted
a
human
health
risk
assessment
for
asulam
for
the
purpose
of
making
a
Tolerance
Reassessment
Eligibility
Decision.
HED
evaluated
the
toxicology,
residue
chemistry,
and
residential
databases
for
asulam
and
determined
that
the
data
are
adequate
to
support
a
Tolerance
Reassessment
Eligibility
Decision
(
TRED).

Use
Profile
Asulam
(
methyl
sulfanilylcarbamate)
is
a
selective,
postemergent
systemic,
carbamate
herbicide
whose
chemical
structure
and
biological
properties
differ
considerably
from
those
of
carbamate
insecticides.
It
is
structurally
related
to
chlorpropham
and
phenmedipham.
It
has
no
registered
residential
uses.
Therefore,
potential
residential
exposures
are
not
anticipated
as
a
result
of
applications
of
asulam.
Use
sites
include
sugarcane
(
the
only
registered
food
use),
Christmas
tree
plantings,
turf
(
for
sod
only),
ornamentals
(
junipers
&
yews
only),
and
non­
crop
land
(
e.
g.,
rights­
of­
way,
fence
rows,
etc.).
Sugarcane
represents
95
percent
of
asulam
utilization;
therefore,
the
remaining
five
percent
is
utilized
on
the
other
use
sites.

Hazard
Profile
The
toxicity
database
for
asulam
included
asulam
technical
(
98
­
100%
ai)
and
the
sodium
salt
of
asulam
(
88%
ai).
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.

Subchronic
and
chronic
toxicity
studies
demonstrate
that
the
thyroid
gland
is
a
target
organ
for
asulam
in
the
rat
and
dog.
Thyroid
findings,
consisting
of
hyperplastic
changes
in
thyroid
follicular
cells
in
male
rats
reported
in
a
two­
year
combined
chronic/
oncogenicity
feeding
study
were
observed
at
the
lowest­
observed­
adverse­
effect­
level
(
LOAEL)
of
180
mg/
kg/
day;
the
no­
observed­
adverse­
effect­
level
(
NOAEL)
was
36
mg/
kg/
day.
The
chronic
RfD
for
asulam
is
derived
from
the
NOAEL
of
36
mg/
kg/
day,
based
on
thyroid
follicular
hyperplasia
at
180
and
953
mg/
kg/
day.
An
uncertainty
factor
of
100
was
applied
to
the
NOAEL
for
interspecies
extrapolation
and
intraspecies
variability.
Thyroid
weights
were
not
monitored
in
the
study.

Other
toxicological
effects
included
adrenal
medullary
hyperplastic
alterations
in
male
rats,
and
decreased
body
weight
gains
in
male
and
female
rats.
In
a
six­
month
dog
study,
increased
thyroid
weights
(
elevated
absolute
weights
in
females
at
300
mg/
kg/
day
and
elevated
absolute
and
relative
weights
in
males
and
females
at
1500
mg/
kg/
day)
were
reported.
Similar
findings
were
noted
in
a
three­
month
gavage
study
in
the
dog.
Asulam
is
classified
as
Group
C,
possible
human
carcinogen,
based
on
thyroid
and
adrenal
tumors
in
the
rat
study.
The
Cancer
Peer
Review
Committee
determined
that
a
low
dose
linear
extrapolation
risk
model
was
not
appropriate
for
asulam
(
memorandum
dated
2/
17/
88).
The
12/
06/
01
HIARC
document,
has
concluded
that
the
submission
and
review
of
a
new
mouse
study
did
not
impact
the
current
classification
of
asulam
as
a
Group
C,
possible
human
carcinogen
or
the
CARC
conclusion
that
a
cancer
risk
assessment
is
not
required.

A
two­
generation
reproduction
study
in
the
rat
study
provided
evidence
for
a
quantitative
increased
susceptibility
of
the
rat
fetus
to
asulam
exposure
relative
to
adults.
Additionally,
the
HIARC
determined
that
a
comparative
thyroid
rat
assay
in
adults
and
offspring
be
conducted.
In
the
rat
reproductive
toxiciity
study,
significantly
fewer
mean
live
births
per
litter
were
observed
at
250
mg/
kg/
day
and
1250
mg/
kg/
day
in
the
first
generation.
A
dose­
response
relationship
was
evident.
The
LOAEL
for
offspring
effects
was
250
mg/
kg/
day.
No
effects
on
mean
live
births
per
litter
were
observed
at
50
mg/
kg/
day,
the
NOAEL
for
offspring
toxicity.
The
LOAEL
for
parental
systemic
toxicity
is
1250
mg/
kg/
day
and
was
based
on
decreased
body
weights
(
F0
males,
F1
females)
and
organ
weight
effects
(
increased
absolute
and
relative
thyroid
weights
in
F1
males
and
F2
males
and
females;
increased
absolute
and
relative
liver
weights
in
F1
females;
and
increased
ovarian
weights
in
F1
females
at
31
days
old,
but
not
at
terminal
necropsy).
The
NOAEL
for
parental
systemic
toxicity
is
250
mg/
kg/
day.

Asulam
has
been
evaluated
for
potential
developmental
effects
in
the
rat
and
the
rabbit.
There
was
no
indication
of
treatment­
related
effects
on
developmental
parameters
(
at
dose
levels
up
to
750
mg/
kg/
day)
in
a
developmental
toxicity
study
in
the
rabbit.
In
the
developmental
study
in
the
rat,
a
slight­
to­
moderate
increase
in
preimplantation
loss
was
observed
at
the
high
dose
level
(
1,500
mg/
kg/
day).
Decreased
maternal
body
weight
gain
was
noted
at
1,500
mg/
kg/
day,
but
not
at
1,000
mg/
kg/
day.
In
a
developmental
toxicity
study
in
the
rabbit,
decreased
maternal
body
weight
gain
was
observed
at
a
LOAEL
of
750
mg/
kg/
day;
the
NOAEL
is
300
mg/
kg/
day.

Asulam
was
tested
in
several
genetic
toxicology
studies,
which
included
assessments
of
gene
mutation,
chromosomal
aberrations,
and
cell
transformation.
All
assays
were
negative.

FQPA
Safety
Factor
Based
upon
the
developmental
studies
reviewed,
there
does
not
appear
to
be
any
quantitative
or
qualitative
evidence
of
increased
susceptibility
of
rat
or
rabbit
fetuses
following
in
utero
exposure
to
asulam.
However,
there
was
evidence
of
quantitative
susceptibility
for
offspring
(
significantly
fewer
mean
live
births)
in
a
two­
generation
reproduction
study
in
the
rat.
Although
neurotoxicity
studies
were
not
performed,
there
was
no
indication
of
neurotoxicity
in
the
submitted
studies
or
in
the
published
literature.
A
developmental
neurotoxicity
study
was
not
required
by
HIARC,
however
a
comparative
thyroid
rat
assay
in
adults
and
offspring
is
being
required.
The
FQPA
Safety
Factor
Committee
(
12/
10/
01)
determined
that
for
asulam,
the
10­
fold
safety
factor
for
the
protection
of
infants
and
children
should
be
retained
because:

1)
There
was
evidence
of
quantitative
susceptibility
in
a
two­
generation
reproduction
study
in
the
rat;
and,
2)
HIARC
recommended
the
requirement
for
a
comparative
thyroid
rat
assay
in
adults
and
offspring
and
this
is
considered
a
data
gap
for
asulam.

3
Toxic
Endpoints
Selected
for
Risk
Assessment
The
HED
Hazard
Identification
Assessment
Review
Committee
(
HIARC)
met
on
11/
13/
01
to
select
endpoints
for
human
health
risk
assessments
and
to
reevaluate
increased
susceptibility
of
offspring
and
fetuses
to
asulam
exposures.
The
quality
of
the
toxicity
studies
for
asulam
provided
reasonable
confidence
in
the
toxicity
endpoints
and
doses
selected
for
risk
assessment.
All
doses
for
risk
assessment
purposes
were
assessed
along
with
the
uncertainty
factors
of
10X
for
interspecies
extrapolation
and
10X
for
intraspecies
variability.

No
acute
dietary
toxicity
endpoint
was
identified
because
no
adverse
effect
attributable
to
a
single
dose
of
asulam
was
observed.
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,
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.
A
chronic
dietary
risk
assessment
was
conducted
to
estimate
risks
from
average
exposures
to
asulam
in
foods.

Short­,
intermediate­,
and
long­
term
dermal
and
inhalation
endpoints
were
selected
because
there
are
occupational
exposures.
Although
dermal
and
inhalation
toxicity
studies
were
available,
these
studies
did
not
include
an
examination
of
the
thyroid
gland,
the
target
organ
for
asulam.
Therefore,
oral
endpoints
were
selected
for
dermal
and
inhalation
endpoints.
Because
the
risk
assessments
conducted
for
this
document
are
intended
to
support
a
TRED,
no
occupational
exposure
and
risk
assessments
were
conducted.

No
endpoints
for
short­,
or
intermediate­
term
incidental
ingestion
were
selected.
Although
dermal
and
inhalation
endpoints
were
selected,
dermal
and
inhalation
risk
assessments
for
residential
exposures
were
not
conducted
because
there
are
no
registered
residential
uses
of
asulam.
Although
asulam
is
classified
as
a
C
carcinogen,
it
has
not
been
quantified
as
per
the
CARC
(
memo
dated
2/
17/
88).
Therefore,
a
quantitative
exposure
and
risk
assessment
for
cancer
has
not
been
conducted.

Chronic
Dietary
Risk
Assessment
The
risk
estimates
for
chronic
dietary
exposures
to
asulam
analyses
reflect
a
refined
exposure
assessment.
Anticipated
residues
(
ARs)
and
percent
crop
treated
information
were
incorporated
in
the
analysis.
ARs
were
calculated
using
field
trial
data.
There
are
no
monitoring
data
(
USDA
PDP)
available
for
asulam.

Chronic
dietary
risk
is
estimated
by
using
average
consumption
and
residue
values.
A
risk
estimate
that
is
less
than
100%
of
the
chronic
Population
Adjusted
Dose
(
cPAD)
does
not
exceed
HED s
level
of
concern.
The
cPAD
(
0.036
mg/
kg/
day)
is
the
RfD
(
0.36
mg/
kg/
day)
divided
by
the
FQPA
safety
factor
(
10x
for
asulam).

Chronic
dietary
risks
estimated
using
a
cPAD
of
0.036
mg/
kg/
day
are
below
the
Agency s
level
of
concern
(<
100%
cPAD)
for
all
population
subgroups.
The
chronic
dietary
risk
estimate
for
children
1­
6
years
(
the
highest
exposed
population
subgroup)
is
1%
of
the
cPAD.
All
other
population
subgroups
have
chronic
dietary
risk
estimates
that
are
<
1%
of
the
cPAD.

4
Drinking
Water
Risk
Assessment
The
Environmental
Fate
and
Effects
Division
(
EFED)
provided
a
drinking
water
assessment
using
simulation
models
to
estimate
the
potential
concentration
of
asulam
and
its
degradates,
sulfanilamide
and
sulfanilic
acid,
in
surface
water.
Sulfanilamide
is
a
major
soil
and
water
degradate
of
asulam
(
Reregsitration
Eligibility
Decision
(
RED)
September
1995).
EFED
used
the
FIRST
reservoir
model
to
calculate
estimated
environmental
concentrations
(
EECs)
in
surface
water.
A
prospective
groundwater
study
was
used
to
estimate
the
groundwater
EEC
for
residues
of
asulam
and
the
sulfanilamide
degradate.
Since
no
data
are
available
on
degradates,
FIRST
modeling
assumed
immediate
conversion
upon
application
to
very
persistent
and
mobile
degradates.

With
respect
to
the
exposure
in
surface
water,
conservative
Tier
I
(
FIRST)
modeling
indicated
that
EECs
in
surface
water
are
not
likely
to
exceed
an
average
concentration
of
6.6
ppb
for
asulam,
and
an
average
concentration
of
272
ppb
for
asulam
plus
the
degradates
(
sulfanilamide
and
sulfanilic
acid)
for
use
in
chronic
exposure
assessments.
Residues
of
asulam
and
sulfanilamide
in
ground
water
are
not
likely
to
exceed
a
maximum
of
154
ppb,
and
an
average
of
43
ppb.
These
EECs
represent
upper
bound
concentrations
for
asulam
residues
in
surface
water
and
groundwater
as
can
be
seen
by
a
comparison
with
monitoring
data
provided
in
the
synopsis
below.

In
a
separate
water
monitoring
study,
asulam
was
detected
in
public
drinking
water
sources
from
ground
and
surface
water.
At
the
request
of
EPA,
Rhone­
Poulenc
conducted
a
drinking
water
monitoring
study
in
areas
of
high
asulam
use
in
Florida
and
Louisiana.
The
surface
water
study
was
designed
to
sample
raw
surface
water
in
up
to
15
community
water
systems
in
Florida
and
4
systems
in
Louisiana.
Samples
were
collected
monthly
for
one
year
and
analyzed
for
asulam
and
the
metabolite
sulfanilamide
at
a
detection
limit
of
1
ppb.
In
addition
to
surface
water
collection,
the
study
collected
samples
from
potable
wells
in
Florida
and
Louisiana
that
were
located
within
1,000
feet
of
an
asulam
treated
area.

Seven
of
the
ten
surface
water
community
systems
sampled
contained
traces
(<
1
ppb)
of
asulam
residues
during
May
through
June.
Four
of
the
community
systems
were
located
in
Louisiana
and
three
were
in
Florida.

A
total
of
28
drinking
water
wells
were
sampled
in
Florida.
Because
of
poor
water
quality
in
this
area
of
Florida,
many
of
the
wells
reportedly
use
some
type
of
treatment
system
prior
to
use.
Three
wells
contained
quantifiable
asulam
residues
up
to
1.92
ppb.
Ten
other
wells
contained
detectable
traces
(<
1
ppb).
Reportedly,
the
depth
of
the
well
and
distance
to
treated
area
did
not
have
any
statistically
significant
effects
on
the
concentrations
observed.
No
residues
were
detected
in
12
wells
sampled
in
the
"
sandier"
areas
of
Hendry
County.
Rhone­
Poulenc
reported
that
there
was
less
intensive
use
of
asulam
in
this
area.
No
residues
were
detected
in
ground
water
samples
in
Louisiana.

Occupational
Risk
Assessment
Because
this
assessment
is
a
TRED,
occupational
handler
and
post
application
scenarios
will
not
be
assessed.

Residential
Risk
Assessment
5
Potential
residential
exposures
are
not
anticipated
as
a
result
of
applications
of
asulam.
All
end
use
product
labels
contain
the
following
statements:
 
FOR
AGRICULTURAL
OR
COMMERCIAL
USE
ONLY 
and
 
NOT
FOR
USE
BY
HOMEOWNERS .
Use
sites
include
sugarcane,
Christmas
tree
plantings,
turf
(
for
sod
only),
ornamentals
(
junipers
&
yews
only),
and
non­
cropland
(
e.
g.
rights­
of­
way,
fence
rows,
etc.).
Sugarcane
represents
95
percent
of
asulam
utilization;
so
therefore,
the
remaining
five
percent
is
utilized
on
the
other
use
sites.
Based
on
the
registrants
total
estimate
of
235,000­
245,000
gallons
of
asulam
sold
and
used
annually
in
the
US,
the
amount
used
annual
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.
In
summation,
residential
exposures
are
considered
unlikely.

Aggregate
Risk
Assessment
In
examining
aggregate
exposure,
HED
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).
Risk
assessments
for
aggregate
exposure
consider
both
short­,
intermediate­
and
long­
term
(
chronic)
exposure
scenarios
considering
the
toxic
effects
which
would
likely
be
associated
with
each
exposure
duration.
There
are
no
residential
uses
of
asulam.
Therefore,
the
considerations
for
aggregate
exposure
are
those
from
food
and
water.
Since
modeling
was
done
to
estimate
concentrations
in
drinking
water,
Drinking
Water
Levels
of
Comparison
(
DWLOCs)
were
calculated.
A
DWLOC
is
a
theoretical
upper
concentration
limit
for
a
pesticide
in
drinking
water
based
on
how
much
of
the
PAD
remains
once
exposures
in
food
and
in
the
home
have
been
estimated
and
subtracted.
For
asulam,
only
chronic
DWLOCs
were
calculated
since
an
acute
endpoint
was
not
selected.
HED
compares
DWLOCs
to
surface
water
and
groundwater
EECs.
If
the
EECs
for
residues
of
asulam
in
surface
water
and
groundwater
are
less
than
the
DWLOCs
for
residues
of
asulam,
HED
has
no
concern
for
aggregate
exposures
to
asulam
residues
in
food
and
drinking
water.

Upon
comparison
of
the
chronic
DWLOCs
(
1,254
ppb
for
males;
1,075
ppb
for
females;
355
ppb
for
children)
with
the
EECs
for
residues
of
asulam
in
surface
and
groundwater,
all
EECs
are
less
than
the
chronic
DWLOCs
for
all
populations.
Consequently,
HED
has
no
concerns
for
chronic
exposures
to
combined
residues
of
asulam
in
food
and
drinking
water,
regardless
of
the
drinking
water
source
(
surface
water
or
groundwater).

Table
1.
Chronic
DWLOCs
Compared
to
Surface
Water
and
Groundwater
EECs
Population
Subgroups
DWLOCs
(
ppb)
Surface
Water
EEC
(
ppb)
(
average
concentration)
Groundwater
EEC
(
ppb)
(
maximum/
average
concentration)

Adult
males
1254
6.6
(
asulam)/
272
(
asulam
+
degradates)
154
(
maximum)/
43
(
average)

Adult
females
1075
6.6
(
asulam)/
272
(
asulam
+
degradates)
154
(
maximum)/
43
(
average)

6
Children
(
1
to
6
years
old)
335
6.6
(
asulam)/
272
(
asulam
+
degradates)
154
(
maximum)/
43
(
average)

2.0
Physical/
Chemical
Properties
Characterization
Asulam
(
methyl
sulfanilylcarbamate)
is
an
herbicide
used
for
weed
control
on
sugarcane.
Asulam
is
formulated
into
and
applied
as
the
asulam
sodium
salt.

H2
N
OH
NO
S
CH3
OO
Asulam
Empirical
Formula:

Molecular
Weight:

CAS
Registry
No.:

Shaughnessy
No.:
H2
N
O
Na+
NO
S
CH3
OO
Asulam,
sodium
salt
C8
H10
N2
O4
S
(
asulam)
C8
H9
N2
NaO4
S
(
asulam
sodium
salt)
230.2
(
asulam)
252.2
(
asulam
sodium
salt)
3337­
71­
1
(
asulam)
2302­
17­
2
(
asulam
sodium
salt)
106901
(
asulam)
106902
(
asulam
sodium
salt)

Asulam
is
a
colorless
crystalline
solid
with
a
melting
point
of
143­
145
EC.
Asulam
sodium
salt
is
a
buff­
colored
powder
with
a
melting
point
of
212­
215
EC.
Asulam
is
soluble
at
approximately
0.5%
in
water,
and
moderately
soluble
in
chlorinated
hydrocarbons,
petroleum
oils,
and
hydroxylic
solvents.
Asulam
sodium
salt
is
soluble
at
>
100
g/
100
mL
in
water
at
pHs
5,
6.5,
and
9.

3.0
Hazard
Characterization
3.1
Hazard
Profile
Toxicology
data
are
used
by
HED
to
assess
the
potential
hazards
to
humans.
The
data
are
derived
from
a
variety
of
acute,
subchronic,
and
chronic
toxicity
tests;
developmental/
reproductive
tests;
and
tests
to
assess
mutagenicity
and
pesticide
metabolism.
The
database
for
asulam
is
adequate
to
support
this
TRED
7
Acute
toxicity
values
and
toxicity
categories
for
asulam
are
summarized
in
Table
2.
The
data
indicate
that
asulam
has
low
acute
oral
(
category
IV),
dermal
(
category
III),
and
inhalation
(
category
IV)
toxicity.
Asulam
is
category
III
with
respect
to
ocular
irritation.
It
is
not
a
dermal
sensitizer.
A
primary
dermal
irritation
study
shows
that
asulam
is
category
III.

Study
Type
Table
2.
Acute
Toxicity
of
Asulam
MRID
No.:
Result
81­
1.
Acute
Oral
Toxicity
­
rat.
Rhone­
Poulenc
Ag
Co.,
Study
No.:
51­
260,
November
7,
1988
409605­
01
LD50
>
5000
mg/
kg.
Toxicity
Category
IV
Classification:
Guideline
81­
2.
Acute
Dermal
Toxicity
­
rabbit.
Rhone­
Poulenc
Ag
Co.,
Study
No.:
51­
260,
November
8,
1988
409605­
01
LD50
>
4000
mg/
kg.
Toxicity
Category
III
Classification:
Guideline
81­
3.
Acute
Inhalation
Toxicity
­
rat.
Rhone­
Poulenc
Ag
Co.,
Study
No.:
51­
583,
November
7,
1988
409605­
02
413616­
01
LC50
>
5
mg/
L
Toxicity
Category
IV
Classification:
Minmum
81­
4.
Primary
Ocular
Irritation
­
rabbit.
Rhone­
Poulenc
Ag
Co.,
Study
No.:
R.
Tox.
57,
June
1981
00098534
Some
chemosis,
redness,
and
irritation
were
noted,
but
eyes
were
clear
by
day
7.
Toxicity
Category
III
Classification:
Minimum
81­
5.
Primary
Dermal
Irritation
­
rabbit.
Rhone­
Poulenc
Ag
Co.,
Study
No.:
RES
2853,
March
1977
00098535
No
dermal
irritation
was
observed.
Toxicity
Category
III
Classification:
Minimum
81­
6.
Dermal
Sensitization
­
guinea
pig.
Rhone­
Poulenc
Ag
Co.,
Study
No.:
RES
2853,
March
1977
00098535
No
evidence
of
sensitization
in
the
Guinea
Pig.
Classification:
Minimum.

No
subchronic
oral
toxicity
studies
in
the
rodent
per
se
were
identified
in
the
data
base
for
asulam.
However,
the
chronic
oral
studies
in
the
rodent
provided
frequent
monitoring
of
clinical
signs
and
interim
measurements
of
body
weights,
food
consumption,
hematology,
clinical
chemistry
and
urinalysis,
and
the
results
provided
insight
into
potential
subchronic
effects.

In
a
subchronic
oral
(
90­
day)
study,
dogs
displayed
increased
thyroid
weights.
Although
the
study
was
classified
as
 
unacceptable
guideline ,
it
was
supported
by
the
findings
of
the
6­
month
oral
dog
study.
The
results
of
the
two
studies
were
similar
(
i.
e.,
the
LOAEL
and
NOAEL
based
on
increased
thyroid
weights).

A
one­
month
inhalation
toxicity
study
and
21­
day
dermal
toxicity
study
were
available;
however,
neither
study
included
assessment
of
thyroid
weights
and
pathology.
The
data
base
for
8
subchronic
toxicity
is
considered
complete
for
oral
and
dermal
studies.
A
28­
day
subchronic
inhalation
study
is
required,
one
that
includes
examination
of
thyroid
weights
and
thyroid
pathology.

The
21/
28­
day
dermal
toxicity
study
in
the
rat
showed
that
no
apparent
treatment­
related
systemic
effects
were
observed
when
body
weight,
food
consumption,
clinical
pathology,
organ
weights,
ophthalmology,
urinalysis,
and
histopathology
were
examined.
Also,
local
skin
irritation,
which
was
slight
and
transient,
was
observed
in
a
small
number
of
treated
females.

There
are
no
90­
day
inhalation
toxicity
studies
available
on
asulam.
However,
a
one­
month
inhalation
toxicity
study
(
MRID
#
00098537)
in
the
rat
was
available.
This
study
is
limited
because
of
the
lack
of
thyroid
weight
measurements
and
pathological
examination
of
the
thyroid.

Developmental
studies
in
rats
and
rabbits,
designed
to
identify
possible
adverse
effects
on
the
developing
organism
which
may
result
from
the
in
­
utero
exposure
to
the
pesticide
were
also
conducted.
The
data
base
for
prenatal
developmental
toxicity
is
considered
complete.
The
prenatal
developmental
toxicity
study
in
the
rat
showed
that
there
were
no
treatment­
related
effects
on
other
maternal
parameters
including
mortality,
clinical
signs,
and
food
consumption.
A
slight
to
moderate
increase
(
not
statistically
significant)
in
preimplantation
loss
was
observed
in
the
mid­
and
high­
dose
groups
(
compared
to
controls).
The
slight
increase
in
postimplantation
loss
at
the
high
dose
(
1500
mg/
kg/
day)
was
not
statistically
significantly
different
from
control
values,
and
was
not
of
any
apparent
biological
significance.

In
the
prenatal
developmental
toxicity
study
in
rabbits,
the
high
dose
selected
was
1,500
mg/
kg/
day.
However,
severe
maternal
toxicity
(
greater
than
20%
weight
loss,
mortality,
and
signs
of
starvation)
occurred
after
administration
of
the
1,500
mg/
kg/
day
dose
level.
All
animals
in
this
group
died
or
were
sacrificed
for
humane
reasons.
A
new
group
was
added
to
the
study
using
a
lower
dose
of
750
mg/
kg/
day.
Mean
maternal
body
weight
gain
was
markedly
reduced
(
35%
but
not
statistically
significant)
in
the
750
mg/
kg/
day
group
than
in
controls
during
the
dosing
period.
In
addition,
mean
maternal
body
weight
gains
were
markedly
reduced
during
days
5­
9,
5­
13,
and
5­
17.
During
the
postdosing
period,
mean
body
weights
of
rabbits
treated
with
750
mg/
kg/
day
were
comparable
to
those
of
controls,
and
rabbits
displayed
some
improvement
in
body
weight
gain.
Rabbits
given
750
mg/
kg/
day
exhibited
a
non­
statistically
significant
decrease
in
food
consumption
at
several
intervals
during
dosing.
There
were
no
apparent
treatment­
related
effects
on
mortality
or
clinical
signs.

The
data
base
for
reproductive
toxicity
is
considered
complete.
No
additional
studies
are
required
at
this
time.
Systemic
effects
observed
at
the
high
dose
(
25,000
ppm)
included
decreased
body
weights
in
F0
males
and
F1
females,
increased
absolute
and/
or
relative
thyroid
weights
in
F1
males
and
F2
males
and
females,
increased
absolute
and
relative
liver
weights
in
F1
females,
and
increased
ovarian
weights
in
F1
females
(
at
age
31
but
not
at
terminal
necropsy).
The
LOAEL
for
systemic
toxicity
is
25,000
ppm
(
1250
mg/
kg/
day)
based
on
decreased
body
weights
(
F0
males,
F1
females)
and
organ
weight
effects
(
increased
absolute
and
relative
thyroid
weights
F1
males
and
F2
males
and
females,
increased
absolute
and
relative
liver
weights
in
F1
females,
and
increased
ovarian
weights
in
F1
females
at
31
days
old
but
not
at
terminal
necropsy).

9
The
data
base
for
chronic
toxicity
is
considered
complete.
No
additional
studies
are
required
at
this
time.
In
the
six­
month
chronic
toxicity
study
in
the
dog,
there
was
no
apparent
relationship
between
test
material
administration
and
mortality.
Treatment­
related
findings
included
reductions
in
body
weight
gains
and
food
consumption
in
the
high­
dose
males
and
females;
increased
frequency
of
emesis
and
diarrhea
in
the
high­
dose
males
and
females;
increased
absolute
thyroid
weights
in
the
mid­
and
high­
dose
females
and
in
the
high­
dose
males;
increased
relative
(
to
body
weight)
thyroid
weights
in
the
high­
dose
males
and
females;
decreased
absolute
testes
and
lung
weights
in
the
high­
dose
males;
decreased
relative
testes
weights
in
the
high­
dose
males;
and
increased
relative
kidney
weights
in
the
high­
dose
males.
No
histopathological
effects
of
toxicological
significance
were
observed.
There
were
no
apparent
effects
on
prothrombin
time,
kaolin
partial
thromboplastin
time
or
platelet
counts
in
males.
Platelet
counts
were
slightly
decreased
in
treated
females;
however,
the
decreases
were
not
dose­
related
at
most
intervals
and
control
values
appeared
to
be
slightly
elevated.
Platelet
count
in
the
high­
dose
females
was
significantly
lower
at
the
26­
week
interval
only.
Plasma
and
brain
cholinesterase
activities
were
not
affected
by
treatment
in
either
sex.

The
carcinogenicity
data
base
for
asulam
is
considered
complete.
There
is
one
acceptable
combined
chronic
toxicity/
oncogenicity
dietary
study
in
the
rat,
and
one
acceptable
oncogenicity
dietary
study
in
the
mouse.
In
a
two­
year
combined
chronic
feeding/
carcinogenicity
study
in
the
rat,
there
was
a
statistically
significant
increase
in
thyroid
gland
C­
cell
carcinomas
in
both
the
low­
and
mid­
dose
males.
There
was
also
a
statistically­
significant
increase
in
adrenal
medullary
pheochromocytomas
at
the
high
dose
in
males.
With
the
exception
of
a
non­
dose­
related
enlargement
of
the
pituitary
gland
in
female
rats,
no
unusual
toxicological
findings
occurred
in
the
animals
sacrificed
at
78
weeks.

In
the
two­
year
carcinogenicity
toxicity
study
in
the
mouse,
increased
mortality
was
observed
in
the
high­
dose
females;
however,
the
number
of
high­
dose
females
was
adequate
to
assess
the
carcinogenic
potential
of
asulam.
There
was
no
treatment­
related
effect
on
food
consumption.
Hematologic
findings
in
the
high­
dose
males
and
females
consisted
of
increased
leukocyte
counts,
decreased
erythrocyte
counts,
and
decreased
hematocrit
levels.
Organ
weight
changes
included
decreased
brain
weight
in
the
high­
dose
females,
and
increased
spleen
weight
in
the
high­
dose
males.
There
was
an
increased
incidence
of
brown
granular
pigment
deposits
in
the
livers
of
males
of
all
treatment
groups
and
high­
dose
females.
Increased
incidences
of
brown
granular
pigment
deposits
were
also
noted
in
the
spleens
of
the
high­
dose
rats
of
both
sexes.
The
brown
granular
pigment
deposit
was
not
identified,
and
is
therefore
of
uncertain
toxicological
significance.
There
was
no
increase
in
the
incidence
of
any
tumors.

With
the
exception
of
the
dominant
lethal
mutation
assay
in
mice,
all
other
mutagenicity
assays
were
found
to
be
acceptable.
These
studies
satistfy
the
pre­
1991
guideline
requirements
for
mutagenicity
studies;
no
further
testing
is
required
at
this
time.
The
data
indicate
that
there
is
no
mutagenicity/
genetic
toxicity
concern.

No
acute,
subchronic,
or
developmental
neurotoxicity
studies
have
been
conducted.
However,
there
is
no
evidence
of
neurotoxicity
in
the
available
acute,
subchronic,
chronic,
and
oncogenicity
studies.
In
the
March
31,
1998
HIARC
meeting,
the
HIARC
concluded:
 
The
data
and
information
provided
by
the
Registrant
demonstrate
that
Asulam,
being
a
carbamate
herbicide
10
rather
than
a
carbamate
insecticide,
has
chemical
structure
and
biological
properties
considerably
different
from
those
of
the
insecticides.
Several
studies
were
cited
to
illustrate
the
lack
of
cholinesterase
inhibition
and
the
absence
of
clinical
signs
suggestive
of
neurotoxicity.
Based
on
these
factors,
the
Agency
waived
the
requirements
for
acute,
subchronic,
and
developmental
neurotoxicity
studies
(
memorandum,
L.
Taylor
to
C.
Peterson,
dated
January
29,
1992. 

The
data
base
for
metabolism
is
considered
to
be
complete.
No
additional
studies
are
required
at
this
time.
The
urinary
route
is
the
predominant
route
of
elimination
in
the
rat.

Table
3.
Toxicology
Profile
for
Asulam
Guideline
No./
Study
Type
MRID
No.
(
year)/
Classification
/
Doses
Results
870.3100
90­
Day
oral
toxicity
in
rodents
See
combined
chronic
feeding
and
carcinogenicity
study.
See
combined
chronic
feeding
and
carcinogenicity
study.

870.3150
90­
Day
oral
toxicity
in
nonrodents
00056414
(
1968)/
Unacceptable/
Guideline/
0,
5,
50
or
500
mg/
kg/
day.
LOAEL
=
500
mg/
kg/
day,
based
on
increased
absolute
and
relative
thyroid
weights
in
male
and
female
dogs.

NOAEL
=
50
g/
kg/
day
870.3200
21­
Day
dermal
toxicity
in
rabbits
41076901
(
1989)
Acceptable/
Guideline/
0
or
1000
mg/
kg/
day.
NOAEL
=
1000
g/
kg/
day
870.3250
90­
Day
dermal
toxicity
No
study.
No
study.

870.3465
90­
Day
inhalation
toxicity
No
study.
No
study
870.3700a
Prenatal
developmental
in
rodents
00098538/(
1981)/
Accept­
able/
guideline/
0,
500,
1,000,
or
1,500
mg/
kg/
day
Maternal
l
LOAEL
=
1,500
mg/
kg/
day
based
on
body
weight
gain
decrement.
aternal
Maternal
NOAEL
=
1,000
mg/
kg/
day.

Developmental
LOAEL
=
1,500
mg/
kg/
day
based
on
slight
to
moderate
increase
in
preimplantation
loss.
Developmental
NOAEL
=
1,000
mg/
kg/
day.

870.3700b
Prenatal
developmental
in
rabbits
00098539/
1981/
Acceptable/
Guideline/
0,
60,
300,
or
750
mg/
kg/
day
Maternal
LOAEL
=
750
mg/
kg/
day
based
on
decreased
body
weight
during
the
dosing
period.

Maternal
NOAEL
=
300
mg/
kg/
day.

Developmental
NOAEL
=
750
mg/
kg/
day.
m
m
The
m
11
Guideline
No./
Study
Type
MRID
No.
(
year)/
Classification
/
Doses
Results
870.3800
Reproduction
and
fertility
effects
00098540/
1981/
Acceptable/
0,
50,
250
or
1250
mg/
kg/
day.
Parental/
Systemic
LOAEL
=
1250
g/
kg/
day
(
HDT)
based
on
decreased
body
weights
(
F0
males,
F1
females)
and
organ
weight
effects
(
increased
absolute
and
relative
thyroid
weights
in
F1
males
and
F2
males
and
females,
increased
absolute
and
relative
liver
weights
in
F1
females,
and
increased
ovarian
weights
in
F1
females
at
31
days
old
but
not
at
terminal
necropsy).

Parental/
Systemic
NOAEL
=
250
mg/
kg/
day.

Reproductive/
Offspring
LOAEL
=
250
mg/
kg/
day
based
on
decreased
mean
live
births
per
litter.

Reproductive/
Offspring
NOAEL
=
50
mg/
kg/
day.

870.4100a
Chronic
toxicity
rodents
See
combined
chronic
feeding
and
carcinogenicity
study.
See
combined
chronic
feeding
and
carcinogenicity
study.

870.4100b
Chronic
toxicity
dogs
00098536/
1979/
Acceptable/
Nonguideline/
0,
60,
300,
or
1,500
mg/
kg/
day.
LOAEL
=
g/
kg/
day,
based
on
significant
(
p
<
0.05)
increases
in
absolute
thyroid
weights
in
females.
Absolute
and
relative
thyroid
weights
were
elevated
at
the
high­
dose
(
1500
mg/
kg/
day)
in
both
males
and
females.
roid
weights
in
the
mid­
and
high­
dose
females
appeared
dose
related.

NOAEL
=
60
mg/
kg/
day.

870.4200
Combined
Chronic
Feeding
and
Carcinogenicity
rats
00098543/
1981/
Acceptabl
e­
Guideline/
0,
36,
180
and
953
mg/
kg/
day
in
males
and
0,
47,
243
and
1,280
mg/
kg/
day
in
females.
LOAEL
=
180
mg/
kg/
day,
based
on
hyperplastic
changes
in
the
adrenal
medulla
and
in
thyroid
follicular
cells
of
males.

NOAEL
=
36
mg/
kg/
day.
Under
the
conditions
of
this
study,
there
was
evidence
of
an
increase
in
tumor
incidence
in
males
when
compared
to
controls.
Therefore,
asulam
is
a
potential
oncogen
in
this
study.
m
300
m
The
increased
absolute
thy
12
Guideline
No./
Study
Type
MRID
No.
(
year)/
Classification
/
Doses
Results
870.4300
Carcinogenicity
mice
42338201/
1982/
Acceptable/
Guideline/
0,
74,
730
and
8,040
mg/
kg/
day
in
males
and
0,
95,
938
and
10,353
mg/
kg/
day
in
females
LOAEL
=
8,040
mg/
kg/
day
in
males,
and
10,353
mg/
kg/
day
in
females,
based
on
increased
spleen
weight
and
decreased
body
weight
gain
in
males,
and
decreased
brain
weight
and
survival
in
females.

NOAEL
=
730
mg/
kg/
day
in
males
and
938
mg/
kg/
day
in
females.

Under
the
conditions
of
this
study,
there
was
no
evidence
of
carcinogenicity
of
asulam.

870.4300
Carcinogenicity
mice
00081183/
1978/
Unacceptable/
Guideline/
0,
225,
and
750
mg/
kg/
day.
LOAEL
=
225
mg/
kg/
day,
based
on
enlargement
of
the
spleen
in
females,
decreased
absolute
and
relative
thyroid
weights
in
females,
intestinal
calcification
in
males
and
females,
and
a
dose­
related
increase
in
the
incidence
of
mild
skin/
subcutis
hyperkeratosis
in
males.

NOAEL
was
not
achieved.

Under
the
conditions
of
this
study,
there
was
no
definitive
evidence
of
carcinogenicity
of
asulam.

One­
Month
Inhalation
study
in
the
rat
00098537/
1977/
Accept­
able
Nonguideline/
nose­
only
exposure
at
concentrations
of
0,
1.6,
3.9,
or
15.3
mg/
L
for
4
hours
per
day,
5
days
per
week,
for
4
weeks.
NOAEL
=
15.3
mg/
L
(
HDT).

Oral
Range­
Finding
in
mice
42110002/
1989/
Accept­
able
Nonguideline/
0,
512,
1,673,
5,103,
and
9,022
mg/
kg/
day
for
males,
and
0,
675,
2,263,
6,835,
and
10,828
mg/
kg/
day
for
females
LOAEL
=
9,022
mg/
kg/
day
based
on
decreased
body
weight
and
body
weight
gain
in
males.

NOAEL
is
5,103
mg/
kg/
day.

Gene
Mutation
870.
A
table
presenting
the
mutagenicity
data
base
is
already
included
under
section
4.7.

870.6200a
Acute
neurotoxicity
screening
battery
No
study.
No
study
13
Guideline
No./
Study
Type
MRID
No.
(
year)/
Classification
/
Doses
Results
870.6200b
Subchronic
neurotoxicity
screening
battery
No
study.
No
study.

870.6300
Developmental
neurotoxicity
Not
required.

870.7485
Metabolism
and
pharmaco­
kinetics
41345601
(
1989)
Metabolism
studies
in
the
rat
demonstrate
that
asulam
was
rapidly
eliminated,
primarily
in
the
urine,
following
administration
of
a
single
oral
or
intravenous
dose,
or
after
repeated
intravenous
doses
for
14
days.
No
unusual
localization
of
asulam
occurred
in
tissues.
Unchanged
parent
compound
was
identified
as
the
major
excretory
product,
with
acetylasulam
and
acetylsulphanilamide
as
minor
metabolites.

870.7600
Dermal
absorpt­
ion
No
Study.
No
Study.

14
Table
4.
Mutagenicity/
Genotoxicity
Studies
for
Asulam
Study
Results
Bacterial
mutagenicity
(
Ames
test)
­
Salmonella
typhimurium.
Litton
Bionetics,
Inc.,
Study
No.:
E­
9177,
1983.
MRID
No.:
40415302
Not
mutagenic
with
and
without
metabolic
activation
at
doses
up
to
2000
Fg/
plate.
Classification:
Acceptable­
Guideline
Dominant
lethal
­
Mouse
­
Hess
&
Clark
(
Div.
of
Rhodia),
Study
No.:
SEH­
75,
1975
MRID
No.:
00082250
No
evidence
of
induction
of
dominant
lethal
effect
at
dietary
concentrations
of
1500
or
5000
ppm.
Classification:
Unacceptable
because
purity
information
on
the
test
material
was
not
provided.

In
vitro
cell
transformation
assay
in
C3H/
10T1/
2
cells.
Mason
Research
Institute.
Study
No.:
596­
249­
8,
October
1979.
MRID
No.:
00098542
No
evidence
of
induction
of
morphological
transformation
at
dose
levels
of
256,
512,
1024,
or
2048
Fg/
mL
for
18
hours
exposure.
Cytotoxicity
was
apparent
at
2048
Fg/
mL.
Classification:
Acceptable
(
Nonguideline).

In
vitro
cytogenetics
in
human
lymphocytes.
Litton
Bionetics,
Inc.
Study
No.:
20990,
March
1984.
MRID
No.:
40415301
Cabinet
d Etudes
et
de
Recherches
en
Tox.
Study
No.:
658,
May
10,
1982.
MRID
No.:
00144051
No
evidence
of
induction
of
a
clastogenic
response
at
doses
of
125­
2500
Fg/
mL
(
absence
of
metabolic
activation)
or
250­
2500
Fg/
mL.
Classification:
Acceptable.

3.2
FQPA
Considerations
The
FQPA
Safety
Factor
Committee
evaluated
the
available
hazard
and
exposure
data
for
asulam
on
December
10th
,
2001
and
made
the
recommendation
for
the
FQPA
safety
factor
to
be
used
in
human
health
risk
assessments
(
as
required
by
Food
Quality
Protection
Act
of
August
3,
1996).
The
committee
concluded
that
the
FQPA
safety
factor
be
retained
(
10x)
in
assessing
the
risk
posed
by
this
chemical.

The
Committee
recommended
that
the
FQPA
safety
factor
be
retained
(
10x)
for
the
following
reasons:

 
There
was
evidence
of
quantitative
susceptibility
in
a
two­
generation
reproduction
study
in
the
rat;
and,
 
HIARC
recommended
the
requirement
for
a
comparative
thyroid
rat
assay
in
adults
and
offspring
and
this
is
considered
a
data
gap
for
asulam.

The
safety
factor
is
required
for
all
population
subgroups
when
assessing
chronic
dietary
exposure
since
the
evidence
for
increase
susceptibility
was
seen
in
the
two­
generation
study,
and
the
results
from
the
comparative
thyroid
study,
may
provide
an
endpoint
for
chronic
risk
assessment.

15
3.3
Dose
Response
Assessment
On
November
13,
2001,
the
Health
Effects
Division
(
HED)
Hazard
Identification
Assessment
Review
Committee
(
HIARC)
reviewed
the
recommendations
of
the
toxicology
reviewer
for
asulam
with
regard
to
the
acute
and
chronic
Reference
Doses
(
RfDs)
and
the
toxicological
endpoint
selection
for
use
as
appropriate
in
occupational/
residential
exposure
risks
assessments.
This
is
the
first
re­
evaluation
after
a
1995
RED.

Acute
RfD:
No
appropriate
toxicological
endpoint
clearly
attributable
to
a
single
exposure
was
identified
including
the
oral
developmental
toxicity
studies
in
rats
and
rabbits.

Chronic
RfD:
NOAEL
of
36
mg/
kg/
day
based
on
hyperplastic
changes
in
the
adrenal
medulla
and
in
thyroid
follicular
cells
observed
in
male
rats
at
180
mg/
kg/
day.
An
uncertainty
factor
of
100
was
applied
to
this
endpoint.
This
endpoint
is
of
the
appropriate
route
and
duration
of
exposure
and
applies
to
the
population
of
concern
(
general
population,
including
infants
and
children).

Classification
of
Carcinogenic
Potential:
On
November
12,
1987,
the
Carcinogenicity
Peer
Review
Committee
met
to
discuss
and
evaluate
the
weight­
of­
the
evidence
on
asulam
with
particular
reference
to
its
carcinogenic
potential
(
Peer
Review
of
Asulam
­
memo
date
2/
17/
88).
The
Committee
concluded
that
the
available
data
for
asulam
provided
limited
evidence
for
the
carcinogenicity
of
the
chemical
in
rats,
and
asulam
was
classified
as
a
Category
C
Carcinogen.
The
Committee
recommended
that
the
18­
month
carcinogenicity
mouse
study
(
MRID
00081183;
unacceptable­
guideline)
be
repeated
and
agreed
to
reevaluate
the
classification
when
a
new
mouse
study
on
asulam
was
submitted
and
reviewed.

A
new
mouse
study
(
MRID
#
423382­
01;
discussed
previously)
was
submitted
by
the
registrant
and
reviewed.
The
committee
considered
the
new
mouse
study
to
be
acceptable.
The
dose
levels
tested
in
the
mouse
study
were
considered
to
be
adequate
for
carcinogenicity
testing.
The
high
dose
tested
was
higher
than
the
limit
dose
level
as
specified
under
Subpart
F
of
the
Pesticide
Assessment
Guideline
for
carcinogenicity
testing
in
mice.
The
treatment
did
not
alter
the
spontaneous
tumor
profile
for
this
strain
of
mouse.
The
Committee
concluded
that
the
new
mouse
study
did
not
impact
the
current
classification
of
asulam
as
a
 
Group
C, 
possible
human
carcinogen,
not
requiring
a
quantitative
risk
assessment.

Short­
Term
(
1
Day
­
1
Month)
Incidental
Oral
Exposure:
Since
there
are
no
residential
uses,
toxic
endpoints
were
not
selected.

Intermediate­
Term
(
1­
6
Months)
Incidental
Oral
Exposure:
Since
there
are
no
residential
uses,
toxic
endpoints
were
not
selected.

Dermal
Absorption
Factor:
100%.
There
are
no
dermal
absorption
studies
with
asulam.
Comparison
of
the
developmental
oral
rabbit
study
to
the
dermal
rabbit
study
is
not
appropriate.
The
dermal
rabbit
study
did
not
include
examination
of
the
thyroid,
the
target
organ.

16
Short­
Term
Dermal
(
1
Day
­
1
Month)
Exposure:
For
this
exposure
scenario,
the
two­
generation
reproduction
study
in
the
rat
(
MRID#
00098540)
is
selected
for
risk
assessment
because
the
decreased
mean
live
births
per
litter
occurred
during
days
0
­
30,
which
is
the
appropriate
duration
of
exposure
for
this
risk
assessment.
It
is
also
protective
of
offspring/
reproductive
effects,
and
possibly
protective
of
thyroid
effects.
A
dermal
absorption
study
was
not
available.
A
dermal
absorption
factor
of
100%
will
be
used
for
route­
to­
route
extrapolation.

Intermediate­
Term
Dermal
(
1­
6
Months)
Exposure:
For
this
exposure
scenario,
the
two­
generation
reproduction
study
in
the
rat
(
MRID#
00098540)
is
selected
for
risk
assessment
because
the
decreased
mean
live
births
per
litter
occurred
during
days
0
­
30,
which
is
the
appropriate
duration
of
exposure
for
this
risk
assessment.
It
is
also
protective
of
offspring/
reproductive
effects,
and
possibly
protective
of
thyroid
effects.
A
dermal
absorption
study
was
not
available.
A
dermal
absorption
factor
of
100%
will
be
used
for
route­
to­
route
extrapolation.

Long­
Term
Dermal
(
Longer
than
6
Months)
Exposure:
A
long­
term
dermal
toxicity
study
was
not
available.
In
addition,
there
was
no
dermal
absorption
study.
The
combined
chronic
toxicity/
carcinogenicity
oral
study
in
the
rat
is
of
the
appropriate
duration
of
exposure.
An
inhalation
absorption
factor
of
100%
will
be
used
for
route­
to­
route
extrapolation.

Short­
term
Inhalation
(
1
Day
­
1
Month)
Exposure:
For
this
exposure
scenario,
the
two­
generation
reproduction
study
in
the
rat
(
MRID#
00098540)
is
selected
for
risk
assessment
because
the
decreased
mean
live
births
per
litter
occurred
during
days
0
­
30,
which
is
the
appropriate
duration
of
exposure
for
this
risk
assessment.
It
is
also
protective
of
offspring/
reproductive
effects,
and
possibly
protective
of
thyroid
effects.
An
inhalation
absorption
study
was
not
available.
An
inhalation
absorption
factor
of
100%
will
be
used
for
route­
to­
route
extrapolation.

Intermediate­
term
Inhalation
(
1­
6
Months)
Exposure:
For
this
exposure
scenario,
the
two­
generation
reproduction
study
in
the
rat
(
MRID#
00098540)
is
selected
for
risk
assessment
because
the
decreased
mean
live
births
per
litter
occurred
during
days
0
­
30,
which
is
the
appropriate
duration
of
exposure
for
this
risk
assessment.
It
is
also
protective
of
offspring/
reproductive
effects,
and
possibly
protective
of
thyroid
effects.
An
inhalation
absorption
study
was
not
available.
An
inhalation
absorption
factor
of
100%
will
be
used
for
route­
to­
route
extrapolation.

Long­
term
Inhalation
(
Longer
than
6
Months)
Exposure:
A
long­
term
inhalation
toxicity
study
was
not
available.
In
addition,
there
was
no
inhalation
absorption
study.
The
combined
chronic
toxicity/
carcinogenicity
oral
study
in
the
rat
is
of
the
appropriate
duration
of
exposure.
An
inhalation
absorption
factor
of
100%
will
be
used
for
route­
to­
route
extrapolation.

Margins
of
Exposure
for
Occupational/
Residential
Risk
Assessments:
A
margin
of
exposure
(
MOE)
of
100
is
adequate
for
dermal/
inhalation
occupational
exposure
risk
assessment.
The
acceptable
MOEs
for
non­
occupational
and
dietary
exposures
will
be
determined
by
the
FQPA
SF
Committee.

Recommendation
for
Aggregate
Exposure
Risk
Assessments:
There
are
no
residential
uses
for
asulam.
The
chronic
aggregate
risk
assessment
is
therefore
limited
to
food
and
water.

17
The
specific
doses
and
endpoints
are
summarized
as
follows:

Table
5.
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
NOAEL
=
36
mg/
kg/
day
UF
=
100
FQPA
Safety
Factor
=
10
The
LOAEL
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
Incidental
Oral,
Short­
Term
A
toxicity
endpoint
was
not
selected
because
there
are
no
residential
uses.

Incidental
Oral,
Intermediate­
Term
A
toxicity
endpoint
was
not
selected
because
there
are
no
residential
uses.

Dermal,
Short­
Term
Oral
NOAELa
=
50
mg/
kg/
day
The
LOAEL
was
250
mg/
kg/
day
based
on
significant
decreases
in
mean
live
births
per
litter.
Two
Generation
Reproduction
Study
in
the
rat
Dermal,
Intermediate­
Term
Oral
NOAELa
=
50
mg/
kg/
day
The
LOAEL
was
250
mg/
kg/
day
based
on
significant
decreases
in
mean
live
births
per
litter.
Two
Generation
Reproduction
Study
in
the
rat
Dermal,
Long­
Term
Oral
NOAELa
=
36
mg/
kg/
day
The
LOAEL
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
Inhalation,
Short­
Term
Oral
NOAELb
=
50
mg/
kg/
day
The
LOAEL
was
250
mg/
kg/
day
based
on
significant
decreases
in
mean
live
births
per
litter.
Two
Generation
Reproduction
Study
in
the
rat
Inhalation,
Intermediate­
Term
Oral
NOAELb
=
50
mg/
kg/
day
The
LOAEL
was
250
mg/
kg/
day
based
on
significant
decreases
in
mean
live
births
per
litter.
Two
Generation
Reproduction
Study
in
the
rat
Inhalation,
Long­
Term
Oral
NOAELb
=
36
mg/
kg/
day
The
LOAEL
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
aApply
100%
dermal
absorption
factor
for
route­
to­
route
extrapolation.
bAssume
100%
inhalation
absorption
factor
for
route­
to­
route
extrapolation.

3.4
Endocrine
Disruption
18
EPA
is
required
by
FQPA,
to
develop
a
screening
program
to
determine
whether
certain
substances
(
including
all
pesticide
active
and
other
ingredients)
"
may
have
an
effect
in
humans
that
is
similar
to
an
effect
produced
by
a
naturally
occurring
estrogen,
or
other
such
endocrine
effects
as
the
Administrator
may
designate."
Following
the
recommendations
of
its
Endocrine
Disruptor
Screening
and
Testing
Advisory
Committee
(
EDSTAC),
EPA
determined
that
there
was
scientific
bases
for
including,
as
part
of
the
program,
the
androgen
and
thyroid
hormone
systems,
in
addition
to
the
estrogen
hormone
system.
EPA
also
adopted
EDSTAC s
recommendation
that
the
Program
include
evaluations
of
potential
effects
in
wildlife.
For
pesticide
chemicals,
EPA
will
use
FIFRA
and,
to
the
extent
that
effects
in
wildlife
may
help
determine
whether
a
substance
may
have
an
effect
in
humans,
FFDCA
authority
to
require
the
wildlife
evaluations.
As
the
science
develops
and
resources
allow,
screening
of
additional
hormone
systems
may
be
added
to
the
Endocrine
Disruptor
Screening
Program
(
EDSP).

When
the
appropriate
screening
and/
or
testing
protocols
being
considered
under
the
Agency s
EDSP
have
been
developed,
asulam
may
be
subjected
to
additional
screening
and/
or
testing
to
better
characterize
effects
related
to
endocrine
disruption.

4.0
Exposure
Assessment
and
Characterization
4.1
Summary
of
Registered
Uses
Asulam
(
methyl­
4­
sulfanilylcarbamate)
is
a
postemergent
systemic
carbamate
herbicide
marketed
under
the
trade
name
ASULOX
®
Herbicide
by
Aventis
CropScience.
ASULOX
®
contains
the
sodium
salt
of
asulam
and
is
registered
for
use
on
sugarcane
as
a
3.34
lb/
gal
soluble
concentrate/
liquid
(
SC/
L)
formulation.
This
formulation
may
be
applied
postemergence
as
a
band
or
broadcast
application
using
ground
or
aerial
equipment
or
as
a
spot
treatment.
Apart
from
its
food
use
on
sugarcane,
asulam
is
used
on
christmas
tree
plantations,
ornamentals,
turf
(
sod
farms
only)
and
non­
cropland
uses.

Asulam
is
primarily
used
in
agriculture
with
key
markets
in
Florida
and
Louisiana.
Sugarcane
is
the
major
use
site
for
asulam
(
95%
of
the
market).
The
asulam
use
rate,
for
sugarcane,
ranges
from
2.5
to
3.34
lbs
a.
i./
A
and
can
applied
up
to
two
times
per
year.
For
all
other
uses,
it
can
be
applied
only
once.
The
average
rate
of
2.5
lbs
ai/
acre
is
the
typical
labeled
use
rate
for
Sugarcane.

Apart
from
its
use
on
sugarcane,
asulam
is
used
on
Christmas
tree
plantations,
ornamentals,
turf
(
Sod
Farms
Only)
and
non­
cropland
uses
(
boundary
fences,
fencerows,
hedgerows,
lumberyards,
storage
areas
and
industrial
plant
sites,
and
warehouse
lots).
For
Christmas
trees
and
ornamentals,
the
label
use
rate
is
3.34
lbs
a.
i./
A
and
can
be
applied
once
per
year
as
a
postemergent
treatment.
For
turf,
the
label
use
rate
is
about
2
lbs.
a.
i./
A
and
can
be
applied
once
per
year.
For
non­
cropland
uses,
the
label
use
rate
ranges
between
2.9
lbs
a.
i./
A
to
3.34
lbs
a.
i./
A
and
can
be
applied
once
per
year.

4.2
Dietary
Exposure/
Risk
Pathway
19
4.2.1
Residue
Profile
A
tolerance
is
established
for
negligible
residues
of
asulam
per
se
in/
on
sugarcane
at
0.1
ppm
[
40
CFR
§
180.360].
HED
has
recommended
that
the
tolerance
expression
be
revised
to
include
all
metabolites
containing
the
sulfanilamide
moiety.
An
adequate
enforcement
method
is
available
for
the
determination
of
combined
residues
of
asulam
and
all
metabolites
containing
the
sulfanilamide
moiety
in/
on
sugarcane.

The
qualitative
nature
of
the
residue
in
plants
is
adequately
understood
based
on
sugarcane
metabolism
studies.
The
terminal
residues
of
concern
are
free
and
conjugated
asulam,
sulfanilamide,
N4
­
acetylasulam,
and
N4
­
acetylsulfanilamide
determined
as
a
common
moiety.

The
qualitative
nature
of
the
residue
in
animals
is
adequately
understood
based
on
acceptable
poultry
and
ruminant
metabolism
studies.
The
terminal
residues
of
concern
are
free
and
conjugated
asulam,
sulfanilamide,
N4
­
acetylasulam,
and
N4
­
acetylsulfanilamide
determined
as
a
common
moiety.

4.2.2
Acute
Dietary
An
acute
dietary
risk
assessment
was
not
performed
since
there
was
no
acute
endpoint
identified
by
HIARC.

4.2.3
Chronic
Dietary
The
asulam
chronic
dietary
exposure
assessment
was
conducted
using
the
Dietary
Exposure
Evaluation
Model
(
DEEM
 
)
software
Version
7.73,
which
incorporates
consumption
data
from
USDA s
Continuing
Surveys
of
Food
Intake
by
Individuals
(
CSFII),
1989­
1992.
The
1989­
92
data
are
based
on
the
reported
consumption
of
more
than
10,000
individuals
over
three
consecutive
days,
and
therefore
represent
more
than
30,000
unique
 
person
days 
of
data.
Foods
 
as
consumed 
(
e.
g.,
apple
pie)
are
linked
to
raw
agricultural
commodities
and
their
food
forms
(
e.
g.,
apples­
cooked/
canned
or
wheat­
flour)
by
recipe
translation
files
internal
to
the
DEEM
software.
Consumption
data
are
averaged
for
the
entire
US
population
and
within
population
subgroups
for
chronic
exposure
assessment,
but
are
retained
as
individual
consumption
events
for
acute
exposure
assessment.

Anticipated
residues
were
calculated
using
field
trial
data.
No
monitoring
data
exist
for
asulam.
In
addition,
estimates
of
percent
crop
treated
(%
CT)
generated
by
BEAD
were
used
to
refine
the
assessment.
This
refined
Tier
2/
3
chronic
dietary
risk
assessment
was
conducted
for
all
supported
(
i.
e.,
currently
registered
and
proposed)
asulam
food
uses.

For
chronic
exposure
and
risk
assessment,
an
estimate
of
the
residue
level
in
each
food
or
food­
form
(
e.
g.,
orange
or
orange­
juice)
on
the
commodity
residue
list
is
multiplied
by
the
average
daily
consumption
estimate
for
that
food/
food
form.
The
resulting
residue
consumption
estimate
for
each
food/
food
form
is
summed
with
the
residue
consumption
estimates
for
all
other
food/
food
forms
on
the
commodity
residue
list
to
arrive
at
the
total
estimated
exposure.
Exposure
estimates
20
are
expressed
in
mg/
kg
body
weight/
day
and
as
a
percent
of
the
cPAD.
This
procedure
is
performed
for
each
population
subgroup.

HED
notes
that
there
is
a
degree
of
uncertainty
in
extrapolating
exposures
for
certain
population
subgroups
from
the
general
U.
S.
population
which
may
not
be
sufficiently
represented
in
the
consumption
surveys,
(
e.
g.,
nursing
and
non­
nursing
infants
or
Hispanic
females).
Therefore,
risks
estimated
for
these
population
subgroups
were
included
in
representative
populations
having
sufficient
numbers
of
survey
respondents
(
e.
g.,
all
infants
or
females,
13­
50
years).

Exposures
>
100%
of
the
cPAD
exceed
HED s
level
of
concern.
That
is,
estimated
exposures
above
this
level
are
of
concern,
while
estimated
exposures
at
or
below
this
level
are
not
of
concern.
The
DEEM
analyses
estimate
the
dietary
exposure
of
the
U.
S.
population
and
26
population
subgroups.
The
results
reported
in
Table
6
are
for
the
U.
S.
Population
(
total),
all
infants
(<
1
year
old),
children
1­
6,
children
7­
12,
females
13­
50,
males
13­
19,
males
20+,
and
seniors
55+
years
of
age.
The
results
for
the
other
population
subgroups
are
not
reported
in
Table
6.
This
is
because
the
numbers
of
respondents
in
the
other
subgroups
were
not
sufficient,
and
thus
the
exposure
estimates
for
these
subgroups
contained
higher
levels
of
uncertainty.
However,
the
respondents
in
these
subgroups
were
also
part
of
larger
subgroups
which
are
listed
in
Table
6.
For
example,
nursing
and
non­
nursing
infants
are
included
in
all
infants.
The
subgroups
which
are
broken
down
by
region,
season,
and
ethnicity
are
also
not
included.
This
assessment
concludes
that
for
all
commodities,
the
chronic
risk
estimates
are
below
the
Agency s
level
of
concern
(<
100%
cPAD)
for
the
general
U.
S.
population
(<
1%
of
the
cPAD)
and
all
population
subgroups.
The
chronic
dietary
exposure
estimate
for
children
1­
6
years
[
highest
exposed
population
subgroup]
is
1%
of
the
cPAD.

Table
6.
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%

4.2.4
Cancer
Dietary
A
cancer
dietary
risk
assessment
is
not
required
for
asulam.

4.3
Water
Exposure/
Risk
Pathway
21
The
Environmental
Fate
and
Effects
Division
(
EFED)
provided
a
drinking
water
assessment
using
simulation
models
to
estimate
the
potential
concentration
of
asulam
and
its
degradates,
sulfanilamide
and
sulfanilic
acid,
in
surface
water.
Sulfanilamide
is
a
major
soil
and
water
degradate
of
asulam
(
Reregsitration
Eligibility
Decision
(
RED)
September
1995).
EFED
used
the
FIRST
reservoir
model
to
calculate
estimated
environmental
concentrations
(
EECs)
in
surface
water.
A
prospective
groundwater
study
was
used
to
estimate
the
groundwater
EEC
for
residues
of
asulam
and
the
sulfanilamide
degradate.
Since
no
data
are
available
on
degradates,
FIRST
modeling
assumed
immediate
conversion
upon
application
to
very
persistent
and
mobile
degradates.

With
respect
to
the
exposure
in
surface
water,
conservative
Tier
I
(
FIRST)
modeling
indicated
that
EECs
in
surface
water
are
not
likely
to
exceed
an
average
concentration
of
6.6
ppb
for
asulam,
and
an
average
concentration
of
272
ppb
for
asulam
plus
the
degradates
(
sulfanilamide
and
sulfanilic
acid)
for
use
in
chronic
exposure
assessments.
Residues
of
asulam
and
sulfanilamide
in
ground
water
are
not
likely
to
exceed
a
maximum
of
154
ppb,
and
an
average
of
43
ppb.
These
EECs
represent
upper
bound
concentrations
for
asulam
residues
in
surface
water
and
groundwater
as
can
be
seen
by
a
comparison
with
monitoring
data
provided
in
the
synopsis
below.

In
a
separate
water
monitoring
study,
asulam
was
detected
in
public
drinking
water
sources
from
ground
and
surface
water.
At
the
request
of
EPA,
Rhone­
Poulenc
conducted
a
drinking
water
monitoring
study
in
areas
of
high
asulam
use
in
Florida
and
Louisiana.
The
surface
water
study
was
designed
to
sample
raw
surface
water
in
up
to
15
community
water
systems
in
Florida
and
4
systems
in
Louisiana.
Samples
were
collected
monthly
for
one
year
and
analyzed
for
asulam
and
the
metabolite
sulfanilamide
at
a
detection
limit
of
1
ppb.
In
addition
to
surface
water
collection,
the
study
collected
samples
from
potable
wells
in
Florida
and
Louisiana
that
were
located
within
1,000
feet
of
an
asulam
treated
area.

Seven
of
the
ten
surface
water
community
systems
sampled
contained
traces
(<
1
ppb)
of
asulam
residues
during
May
through
June.
Four
of
the
community
systems
were
located
in
Louisiana
and
three
were
in
Florida.

A
total
of
28
drinking
water
wells
were
sampled
in
Florida.
Because
of
poor
water
quality
in
this
area
of
Florida,
many
of
the
wells
reportedly
use
some
type
of
treatment
system
prior
to
use.
Three
wells
contained
quantifiable
asulam
residues
up
to
1.92
ppb.
Ten
other
wells
contained
detectable
traces
(<
1
ppb).
Reportedly,
the
depth
of
the
well
and
distance
to
treated
area
did
not
have
any
statistically
significant
effects
on
the
concentrations
observed.
No
residues
were
detected
in
12
wells
sampled
in
the
"
sandier"
areas
of
Hendry
County.
Rhone­
Poulenc
reported
that
there
was
less
intensive
use
of
asulam
in
this
area.
No
residues
were
detected
in
ground
water
samples
in
Louisiana.

4.4
Residential
and
Occupational
Exposure/
Risk
Pathway
Because
this
assessment
is
for
a
TRED,
occupational
handler
and
post
application
scenarios
will
not
be
assessed.

22
Potential
residential
exposures
are
not
anticipated
as
a
result
of
applications
of
asulam.
All
end
use
product
labels
contain
the
following
statements:
 
FOR
AGRICULTURAL
OR
COMMERCIAL
USE
ONLY 
and
 
NOT
FOR
USE
BY
HOMEOWNERS .
Use
sites
include
sugarcane,
Christmas
tree
plantings,
turf
(
for
sod
only),
ornamentals
(
junipers
&
yews
only),
and
non­
cropland
(
e.
g.
rights­
of­
way,
fence
rows,
etc.).
Sugarcane
represents
95
percent
of
asulam
utilization;
so
therefore,
the
remaining
five
percent
is
utilized
on
the
other
use
sites.
Based
on
the
registrants
total
estimate
of
235­
245,000
gallons
of
asulam
sold
and
used
annually
in
the
US,
the
amount
used
annual
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.
In
summation,
residential
exposures
are
considered
unlikely.

Spray
drift
is
always
a
potential
source
of
exposure
to
the
public
or
near
spraying
operations.
This
is
particularly
the
case
with
aerial
application,
but,
to
a
lesser
extent,
could
also
be
a
potential
source
of
exposure
from
groundboom
application
methods.
The
Agency
has
been
working
with
the
Spray
Drift
Task
Force,
EPA
Regional
Offices
and
State
Lead
Agencies
for
pesticide
regulation
and
other
parties
to
develop
the
best
spray
drift
management
practices.
The
Agency
is
now
requiring
interim
mitigation
measures
for
aerial
applications
that
must
be
placed
on
product
labels/
labeling.
The
Agency
has
completed
its
evaluation
of
the
new
data
base
submitted
by
the
Spray
Drift
Task
Force,
a
membership
of
U.
S.
pesticide
registrants,
and
is
developing
a
policy
on
how
to
appropriately
apply
the
data
and
the
AgDRIFT
computer
model
to
its
risk
assessments
for
pesticides
applied
by
air,
orchard
airblast
and
ground
hydraulic
methods.
After
the
policy
is
in
place,
the
Agency
may
impose
further
refinements
in
spray
drift
management
practices
to
reduce
off­
target
and
risks
associated
with
aerial
as
well
as
other
application
types
where
appropriate.

5.0
Aggregate
Risk
Assessments
and
Risk
Characterizations
Because
an
acute
toxicity
endpoint
was
not
identified
by
HIARC,
an
acute
aggregate
risk
assessment
is
not
required.

In
examining
aggregate
exposure,
HED
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).
Risk
assessments
for
aggregate
exposure
consider
both
short­,
intermediate­
and
long­
term
(
chronic)
exposure
scenarios
considering
the
toxic
effects
which
would
likely
be
associated
with
each
exposure
duration.
There
are
no
residential
uses
of
asulam.
Therefore,
the
considerations
for
aggregate
exposure
are
those
from
food
and
water.
Since
conservative
modeling
was
done
to
estimate
concentrations
in
drinking
water,
Drinking
Water
Levels
of
Comparison
(
DWLOCs)
were
calculated.
A
DWLOC
is
a
theoretical
upper
concentration
limit
for
a
pesticide
in
drinking
water
based
on
how
much
of
the
PAD
remains
once
exposures
in
food
and
in
the
home
have
been
estimated
and
subtracted.
For
asulam,
only
chronic
DWLOCs
were
calculated
since
an
acute
endpoint
was
not
selected.
HED
compares
DWLOCs
to
surface
water
and
groundwater
EECs.

23
If
the
EECs
for
residues
of
asulam
in
surface
water
and
groundwater
are
less
than
the
DWLOCs
for
residues
of
asulam,
HED
has
no
concern
for
aggregate
exposures
to
asulam
residues
in
food
and
drinking
water.

Upon
comparison
of
the
chronic
DWLOCs
(
1,254
ppb
for
males;
1,075
ppb
for
females;
355
ppb
for
children)
with
the
EECs
for
residues
of
asulam
in
surface
and
groundwater,
all
EECs
are
less
than
the
chronic
DWLOCs
for
all
populations.
Consequently,
HED
has
no
concerns
for
chronic
exposures
to
combined
residues
of
asulam
in
food
and
drinking
water,
regardless
of
the
drinking
water
source
(
surface
water
or
groundwater).

Table
7.
Chronic
DWLOCs
Compared
to
Surface
Water
and
Groundwater
EECs
Population
Subgroups
DWLOCs
(
ppb)
Surface
Water
EEC
(
ppb)
(
average
concentration)
Groundwater
EEC
(
ppb)
(
maximum/
average
concentration)

Adult
males
1254
6.6
(
asulam)/
272
(
asulam
+
degradates)
154
(
maximum)/
43
(
average)

Adult
females
1075
6.6
(
asulam)/
272
(
asulam
+
degradates)
154
(
maximum)/
43
(
average)

Children
(
1
to
6
years
old)
335
6.6
(
asulam)/
272
(
asulam
+
degradates)
154
(
maximum)/
43
(
average)

6.0
Cumulative
The
Food
Quality
Protection
Act
(
1996)
stipulates
that
when
determining
the
safety
of
a
pesticide
chemical,
EPA
shall
base
its
assessment
of
the
risk
posed
by
the
chemical
on,
among
other
things,
available
information
concerning
the
cumulative
effects
to
human
health
that
may
result
from
dietary,
residential,
or
other
non­
occupational
exposure
to
other
substances
that
have
a
common
mechanism
of
toxicity.
The
reason
for
consideration
of
other
substances
is
due
to
the
possibility
that
low­
level
exposures
to
multiple
chemical
substances
that
cause
a
common
toxic
effect
by
a
common
mechanism
could
lead
to
the
same
adverse
health
effect
as
would
a
higher
level
of
exposure
to
any
of
the
other
substances
individually.
A
person
exposed
to
a
pesticide
at
a
level
that
is
considered
safe
may
in
fact
experience
harm
if
that
person
is
also
exposed
to
other
substances
that
cause
a
common
toxic
effect
by
a
mechanism
common
with
that
of
the
subject
pesticide,
even
if
the
individual
exposure
levels
to
the
other
substances
are
also
considered
safe.

Although
asulam
had
been
included
in
the
list
of
potential
carbamates
for
cumulative
risk
assessment
of
carbamates
as
a
group,
it
will
not
be
included
in
the
carbamate
cumulative
assessment.
The
available
data
indicate
that
asulam
is
a
carbamate
herbicide
that
has
chemical
structure
and
biological
properties
that
are
considerably
different
from
those
of
the
carbamate
insecticides.
For
instance,
several
studies
on
asulam
(
e.
g.,
chronic
oral
dog,
combined
chronic
toxicity/
oncogenicity
dietary
rat)
demonstrate
the
lack
of
cholinesterase
inhibition
and
absence
of
clinical
signs
suggestive
24
of
neurotoxicity.
Acute
studies
reveal
a
low
toxicity
for
asulam
(
e.
g.,
no
deaths
and
clinical
signs
of
nonspecific
origin).
There
are
no
specific
mechanism
of
toxicity
studies
on
asulam.

Before
undertaking
any
cumulative
risk
assessment,
HED
will
follow
procedures
for
identifying
chemicals
that
have
a
common
mechanism
of
toxicity
as
set
forth
in
the
 
Guidance
for
Identifying
Pesticide
Chemicals
and
Other
Substances
that
Have
a
Common
Mechanism
of
Toxicity 
(
64
FR
5795­
5796,
February
5,
1999).

25
7.0
Tolerance
Reassessment
Recommendations
7.1
Tolerance
Reassessment
Recommendation
Table
8
summarizes
the
tolerance
reassessment
for
asulam.

Commodity
Table
8.
Tolerance
Reassessment
Summary
Current
Tolerance
(
ppm)
Tolerance
Reassessment
(
ppm)
Comment
Tolerance
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
 
0.05
Cattle,
meat
byproducts
Goat,
meat
byproducts
Hog,
meat
byproducts
Horse,
meat
byproducts
Sheep,
meat
byproducts
 
0.2
8.0
Data
Needs/
Label
Requirements
8.1Toxicology
 
Comparative
thyroid
rat
assay
in
adult
and
offspring.
 
21­
day
Dermal
Study
in
Rats
with
examination
of
thyroid
weight
and
pathology.
 
28­
day
Inhalation
Study
in
Rats
with
examination
of
thyroid
weight
and
pathology.

8.2
Product
and
Residue
Chemistry
26
 
Because
hydroquinone/
quinone
remains
a
chemical
of
toxicological
concern,
if
the
registrant
proposes
new
uses
for
this
chemical,
new
plant
metabolism
studies
m
ust
be
performed
(
relevant
to
the
proposed
new
uses),
aimed
specifically
at
determining
the
presence
and
concentration
of
radiolabeled
hydroquinone/
quinone.
The
registrant
should
also
determine
the
naturally
occurring
background
levels
of
hydroquinone/
quinone
and
arbutin
in
sugarcane.
The
Metabolism
Committee
will
reconsider
its
position
if
new
metabolism
studies
show
that
quinone/
hydroquinone/
arbutin
comprises
a
significant
portion
of
the
radiolabeled
residue.

 
HED
has
recommended
that
the
registrant
request
label
amendments
specifying
a
maximum
of
two
asulam
applications
per
year
to
sugarcane
at
a
maximum
single
application
rate
of
3.34
lbs.
a.
i./
A,
a
PHI
of
100
days
for
Louisiana,
a
PHI
of
140
days
for
the
remainder
of
the
US
mainland,
and
a
PHI
of
400
days
for
Hawaii.
If
the
regsitrant
requests
the
recommended
label
changes,
no
further
sugarcane
field
trial
data
are
required
for
asulam
at
this
time.
If
the
registrant
does
not
propose
the
recommended
label
changes,
existing
labels
must
be
supported
by
new
field
trials.

 
The
following
product
chemistry
data
guidelines
remain
unfulfilled
for
the
technical
asulam
sodium
salt:
GLN
830.6317
(
Storage
Stability)
and
830.6320
(
Corrosion
Characteristics).

 
Tolerance
Reassessment
1.
The
existing
tolerance
of
0.1
ppm
for
asulam
residues
on
sugar
cane
established
in
40
CFR
§
180.360
has
been
reassessed.
HED
recommends
the
tolerance
be
raised
to
1.0
ppm;

2.
HED
recommends
a
tolerance
of
30
ppm
for
asulam
residues
in
molasses
from
sugar
cane
be
established
in
40
CFR
§
180.360;

3.
HED
recommends
a
tolerance
of
0.05
ppm
for
asulam
residues
in
milk,
and
meat
and
fat
from
cattle,
goats,
hogs,
horses,
and
sheep
be
established
in
40
CFR
§
180.360;

4.
HED
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;

5.
Because
there
are
no
poultry
feed
items
associated
with
asulam's
use,
tolerances
on
poultry
tissues
and
eggs
are
not
warranted.

27