Document ID: EPA-HQ-OPP-2006-0206-0002
Agency: epa
Document Type: Supporting & Related Material
Title: 
Posted Date: 2006-07-14T04:00Z

Monsanto
Company
authorizes
the
EPA
to
publish
the
following
summary
of
the
petition
to
comply
with
the
Food
Quality
Protection
Act
of
1996.
An
electronic
copy
on
computer
disc
is
provided
with
the
cover
letter
for
this
submission.

ENVIRONMENTAL
PROTECTION
AGENCY
[
OPP­
XXXX­
XXXX;
FRL­
XXXX­
X]

Sulforsulfuron;
Notice
of
Filing
a
Pesticide
Petition
to
Establish
Tolerances
for
Certain
Pesticide
Chemical
In
or
On
Food
AGENCY:
Environmental
Protection
Agency
(
EPA)
ACTION:
Notice
SUMMARY:
This
notice
announces
the
initial
filing
of
a
pesticide
petition
proposing
the
establishment
of
regulations
for
residues
of
a
certain
pesticide
chemical
in
or
on
various
food
commodities.

DATES:
Comments,
identified
by
docket
identification
(
ID)
number
OPP­
XXXX­
XXXX,
must
be
received
on
or
before
XXXX.

ADDRESSES:
Comments
may
be
submitted
electronically,
by
mail,
or
by
hand
delivery/
courier.
Follow
the
detailed
instructions
as
provided
in
Unit
I,
of
the
SUPPLEMENTARY
INFORMATION.

FOR
FURTHER
INFORMATION
CONTACT:
James
A.
Tompkins
(
PM
25),
Registration
Division
(
7505C),
Office
of
Pesticide
Programs,
Environmental
Protection
Agency,
1200
Pennsylvania
Ave.,
NW,
Washington,
DC
20450­
0001;
telephone
number:
(
703)
308­
9364;
e­
mail
address:
Tompkins.
Jim@
epa.
gov.

****************************

Summary
of
Petition
A
summary
of
the
pesticide
petition
is
printed
below
as
required
by
FFDCA
section
408(
d)(
3).
The
petition
summary
was
prepared
by
the
Petitioner
and
represents
the
views
of
the
Petitioner.
The
petition
summary
announces
the
availability
of
a
description
of
the
analytical
methods
available
to
EPA
for
the
detection
and
measurement
of
the
pesticide
chemical
residues
or
an
explanation
of
why
no
such
method
is
needed.

Monsanto
Company
Pesticide
Petition
(
PP)
xxxxxx
EPA
has
received
PP
xxxxxx
from
Monsanto
Company,
1300
I
Street
NW,
Suite
450
East,
Washington,
DC
20005,
proposing,
pursuant
to
section
408(
d)
of
the
Federal
Food,
Drug
and
Cosmetic
Act,
21
U.
S.
C.
346a(
d),
to
amend
40
CFR
part
180.552
by
establishing
tolerances
for
residues
of
the
herbicide
sulfosulfuron,
1­(
4,6­
dimethoxypyrimidin­
2­
yl)­
3­[(
2­
ethane­
sulfonyl­
imidazo[
1,2­
a]
pyridine­
3­
yl)
sulfonyl]
urea
and
its
metabolites
converted
to
2­(
ethylsulfonyl)
imidazo[
1,2­
a]
pyridine
and
calculated
as
sulfosulfuron
in
or
on
grass
forage
at
13
parts
per
million
(
ppm),
grass
hay
at
14
ppm,
milk
at
0.02
ppm,
fat
(
of
cattle,
goat,
horse
and
sheep)
at
0.03
ppm,
meat
(
of
cattle,
goat,
horse
and
sheep)
at
0.01;
and
meat
byproducts
(
of
cattle,
goat,
horse
and
sheep)
at
0.4
ppm.
EPA
has
determined
that
the
petition
contains
data
or
information
regarding
the
elements
set
forth
in
section
408(
d)
(
2)
of
the
FFDCA;
however,
EPA
has
not
fully
evaluated
the
sufficiency
of
the
submitted
data
at
this
time
or
whether
the
data
supports
granting
of
the
petition.
Additional
data
may
be
needed
before
EPA
rules
on
the
petition.

A.
Residue
Chemistry
1.
Plant
metabolism.
The
nature
of
the
residue
in
wheat
has
been
thoroughly
investigated
and
is
adequately
understood.
Metabolism
of
sulfosulfuron
in
plants
is
negligible;
plant
residues
are
primarily
parent
and
metabolites
containing
the
imidazopyridine
ring.
Postemergence
applications
to
wheat
result
in
residues
that
are
mostly
parent
with
small
amounts
of
5
or
6
metabolites
that
represent
less
than
15%
of
the
TRR.
Tolerance
expressions
take
into
account
these
metabolites
and
are
calculated
as
sulfosulfuron.
It
is
reasonable
that
the
nature
of
the
sulfosulfuron
residue
in
wheat
would
be
the
same
or
similar
in
other
grass
species,
such
as
those
being
considered
in
this
petition.

2.
Analytical
method.
An
analytical
method
utilizing
LC/
MS/
MS
detection
is
available
for
enforcement
purposes.
The
method
involves
acid
hydrolysis
to
ethyl
sulfone,
a
common
chemophore
that
quantifies
all
sulfosulfuron
residues
in
which
the
imidazopyridine
ring
remained
intact.

3.
Magnitude
of
the
residues.
Residue
trials
were
conducted
on
bermudagrass
and
bahaigrass
pastures,
and
rangelands
of
mixed
grasses,
at
12
locations
distributed
across
the
U.
S.
The
nature
of
sulfosulfuron
residue
in
grass
is
adequately
understood
through
the
wheat
(
a
grass)
metabolism
study.
Following
maximum
annual
application
rates,
residue
of
sulfosulfuron
and
its
metabolites
calculated
as
sulfosulfuron
in
grass
forage
ranged
from
0.99 
12.4
ppm
at
0­
days
after
application
(
0­
DAA)
and
from
0.009 
5.7
ppm
14­
DAA,
and
in
from
0.06 
7.23
ppm
in
grass
hay
harvested
14
days
after
application.
These
residue
data
were
the
basis
for
establishing
tolerances
for
grass
forage
and
grass
hay.

B.
Toxicological
Profile
1.
Acute
toxicity.
Acute
toxicity
studies
with
the
technical
grade
of
the
active
ingredient
sulfosulfuron:
Oral
LD50
in
rats
is
greater
than
5000
mg/
kg,
Toxicity
Category
IV;
Dermal
LD50
in
rabbits
is
greater
than
5000
mg/
kg,
Toxicity
Category
IV;
no
mortality
was
observed
in
rats
following
a
4­
hour
inhalation
exposure
at
3.0
mg/
l,
the
highest
attainable
concentration,
Toxicity
Category
IV;
slightly
irritating
to
the
eyes,
Toxicity
Category
III;
not
a
skin
irritant,
Toxicity
Category
IV;
not
a
dermal
sensitizer.

2.
Genotoxicity.
Sulfosulfuron
is
not
considered
to
be
genotoxic.
The
following
genotoxicity
tests
were
all
negative:
Ames
Salmonella
point
mutation
assay
in
five
test
strains;
a
CHO/
HGPRT
mammalian
point
mutation
assay,
an
in
vitro
chromosomal
aberration
test
in
human
lymphocytes;
an
in
vivo
mouse
micronucleus
assay
with
confirmatory
radiolabeled
assay
that
demonstrated
that
the
test
material,
or
a
metabolite,
did
reach
the
bone
marrow.
A
cytogenetics
assay
using
Chinese
Hamster
lung
cells
was
conducted
at
elevated
concentrations
up
to
and
including
5000
µ
g/
ml.
This
high
concentration
in
the
test
media
exceeded
the
solubility
limit
of
sulfosulfuron.
In
this
study,
dose­
dependent
toxicity
was
observed
in
the
presence
of
S9
at
dose
levels
exceeding
solubility
(>
1000
µ
g/
ml),
with
precipitating
test
material
present.
Similarly,
increases
in
chromosome
aberrations
were
only
observed
in
the
absence
of
S9
at
dose
levels
exceeding
solubility
(>
2000
µ
g/
ml)
with
precipitating
test
material
present.
Also,
historical
results
at
this
testing
facility
indicate
that
of
the
substances
tested
there,
46%
induced
chromosomal
aberrations
in
this
assay,
and
that
65%
of
these
had
a
high
incidence
of
chromatid
exchanges
at
both
the
low­
and
highdose
levels.
The
biological
significance
and
the
mechanism
responsible
for
induction
of
toxicity
and
chromosomal
aberrations
only
after
extended
treatment
at
precipitating
dose
levels
are
not
clear.
The
observation
that
an
in
vitro
chromosomal
aberration
test
in
human
lymphocytes
and
an
in
vivo
mouse
micronucleus
assay
were
negative
indicate,
in
this
case,
that
this
in
vitro
CHL
assay
does
not
represent
a
genotoxic
potential
for
sulfosulfuron.

3.
Reproductive
and
developmental
toxicity.

i.
Rat
development
toxicity
study.
Mated
female
Sprague­
Dawley
rats
at
dose
levels
of
0,
100,
300,
and
1000
mg/
kg/
day
on
days
6 
15
of
gestation,
no
signs
of
maternal
toxicity
or
developmental
effects
were
observed
at
any
dose
level
(
NOEL
=
1000
mg/
kg/
day).

ii.
Rabbit
developmental
toxicity
study.
Dose
levels
of
0,
50,
250
and
1000
mg/
kg/
day
on
days
7 
19
of
gestation,
no
signs
of
maternal
or
developmental
effects
were
observed
at
any
dose
level
(
NOEL
=
1000
mg/
kg/
day).
iii.
Two­
generation
rat
reproduction
study.
Sprague­
Dawley
rats,
at
dietary
concentrations
of
0,
50,
500,
5000
and
20000
ppm,
mild
body
weight/
weight
gain
reductions
were
observed
in
adult
animals
and
urinary
tract
microscopic
changes
(
related
to
urolith
formation)
in
adults
and
some
offspring
at
20,000
ppm,
and
there
were
no
treatment
related
adverse
effects
on
any
reproductive
indices
or
pup
survival/
development
at
any
dose
level
(
NOEL
=
5000
ppm
(
312
mg/
kg/
day
in
males
and
378
mg/
kg/
day
in
females)
for
subchronic
toxicity,
and
NOEL
=
20,000
ppm
(
1313
mg/
kg/
day
in
males
and
1598
mg/
kg/
day
in
females)
for
reproductive
toxicity).

4.
Subchronic
toxicity.
Studies
conducted
in
rats,
mice
and
dogs,
with
the
urinary
tract
being
the
primary
target
organ
system
in
all
three
species
tested.

i.
90­
Day
rat
feeding
study.
(
Also
served
as
range­
finding
study
for
reproduction
study.)
Sprague­
Dawley
rats
administered
dietary
concentrations
of
0,
20,
200,
2000,
6000,
and
20,000
ppm,
after
13
weeks
resulted
in
mild
weight/
weight
gain
reductions
at
20,000
ppm;
no
adverse
effects
on
food
consumption,
hematological
or
clinical
chemistry
parameters,
organ
weights,
or
gross
or
microscopic
pathology
observations.
(
NOAEL
=
6000
ppm
(
370
mg/
kg/
day
males
and
448
mg/
kg/
day
females)).

ii.
90­
Day
dog
study.
Gelatin
capsule
dose
0,
30,
100,
300
and
1000
mg/
kg/
day,
5
days
a
week,
showed
no
adverse
effects
on
body
weights,
food
consumption,
or
hematological
or
clinical
chemistry
parameters.
Urinary
bladder/
uretheral
stones
(
calculi)
found
at
1000
mg/
kg/
day
in
one
male
dog;
urinary
tract
gross
and
microscopic
effects
in
females
at
and
above
300
mg/
kg/
day
and
in
males
at
1000
mg/
kg/
day.
(
NOEL
=
300
mg/
kg/
day
male
and
100
mg/
kg/
day
female).

ii.
90­
Day
mouse
study.
Concentrations
of
0,
100,
1000,
3000
and
7000
ppm
were
administered
for
90
days
to
groups
of
20
CD­
1
mice
(
10
males
and
10
females).
There
was
no
indication
of
toxicity
up
to
the
highest
dose
tested
(
7000
ppm).
An
equivocal
decrease
in
serum
alkaline
phosphatase
level
was
present
in
females
at
the
7000­
ppm
dietary
level,
but
the
finding
was
not
considered
treatment
related.
The
no
observed
effect
level
(
NOAEL)
was
considered
to
be
7,000
ppm
(
1144
mg/
kg
body
weight/
day
in
males
and
887
mg/
kg
body
weight/
day
in
females.

5.
Chronic
toxicity
and
oncogenicity.

i.
1­
Year
chronic
dog
study.
Administered
by
gelatin
capsule
at
dose
levels
of
0,
5,
20,
100
and
500
mg/
kg/
day
five
days
per
week.
Urinary
crystals
were
present
in
both
sexes
at
500
mg/
kg/
day
by
mid­
study,
and
a
calculus,
thickened/
irregular
mucosa,
and
red
foci
observed
in
one
male
dog
at
500
mg/
kg/
day
at
the
conclusion
of
the
study.
Mucosal
lesions
were
considered
to
have
been
related
to
the
presence
of
calculus(
i).
As
a
result,
considered
to
have
demonstrated
chronic
toxicity
secondary
to
urinary
crystal
and/
or
calculus
formation
at
a
dose
level
of
500
mg/
kg/
day
in
male
and
female
dogs
(
NOEL
=
100
mg/
kg/
day
for
chronic
toxicity).

ii.
18­
Month
mouse
oncogenicity
study.
CD­
1
mice
fed
diets
containing
0,
30,
700,
300
and
7000
ppm.
Mortality
not
significantly
affected;
treatment­
related
effects
included
clinical
signs
or
urine­
stained
hair,
intra­
abdominal
swellings
and
abnormal
penile
erection;
gross
pathology
findings
of
urinary
calculi
and
related
dilation/
distension/
enlargement
of
urinary
tract
organs
in
male
at
3000
and/
or
7000
ppm.
Statistically
significant
increase
in
mean
serum
levels
of
BUN
in
males
at
7000
ppm
at
the
end
of
the
study
that
was
considered
treatment­
related
and
the
result
of
gross
and
microscopic
renal
effects.
Hyperplasia
of
the
transitional
epithelium,
chronic/
active
inflammation,
dilatation
and/
or
calculi
were
present
in
the
urinary
bladder
of
male
mice
at
3000
and
7000
ppm,
and
squamous
metaplasia
of
the
urinary
bladder
mucosal
was
observed
at
7000
ppm.
In
the
kidneys
of
male
mice,
there
was
an
increase
in
the
incidence
of
atrophy
of
the
cortex
and
dilatation
of
the
renal
pelvis
at
7000
ppm.
All
of
these
effects
were
associated
with
the
presence
of
and/
or
a
direct
result
of
urinary
calculi/
microcalculi.
There
were
no
effects
in
female
mice
at
any
dose
level.
(
Chronic
Toxicity
NOEL
=
700
ppm
(
93.4
mg/
kg/
day)
male
and
7000
ppm
(
1388.2
mg/
kg/
day)
female).
A
small
increase
in
benign
mesenchymal
tumors
of
the
urinary
bladder
mucosa
in
males
at
7000
ppm
was
seen.
(
NOEL
=
3000
ppm
(
393.6
mg/
kg/
day)
male
oncogenic
effects
and
7000
ppm
(
13882
mg/
kg/
day)
in
females).
iii.
Two­
year
combined
rat
chronic
toxicity/
oncogenicity
study.
Sprague­
Dawley
rats
administered
dietary
concentrations
of
0,
50,
500,
5000
and
20,000
ppm,
was
ended
at
day
259
for
the
20,000­
ppm
group
due
to
excessive
mortality,
all
others
sacrificed
at
22
months
due
to
poor
long­
term
survival.
There
were
no
other
treatment­
related
effects
on
survival
and
no
apparent
clinical
signs
of
toxicity.
Treatment­
related
effects
included,
statistically
significant
decreases
in
mean
body
weight
and/
or
cumulative
body
weight
gain
at
20,000
ppm
in
females,
decreased
albumin
and
albumin/
globulin
ratio
at
5000
ppm
males,
abnormal
crystals
in
urine
at
5000
ppm
for
males
and
at
5000
and
20,000
ppm
for
females
(
urinary
tract
calculi
were
observed
in
some
females
at
these
doses),
and
increased
numbers
of
urinary
red
blood
cells
and/
or
occult
blood
at
20,000
ppm
for
both
sexes.
Gross
necropsy
findings
considered
to
be
treatment
related
in
females
at
5000
and
20,000
ppm
were,
renal
calculi,
renal
pelvic
dilatation,
and
granular/
pitted/
irregular
kidney
surface;
urinary
bladder
calculi;
ureteral
calculi,
ureter
dilatation,
and
abnormal
contents;
and
thyroid/
parathyroid
enlargement.
Microscopic
effects
in
kidney,
urinary
bladder,
and
ureter
of
females
included
renal
pelvic
calculus/
microcalculus,
pelvic
dilatation,
pelvic
epithelial
hyperplasia,
squamos
metaplasia,
pyelonephritis,
and
increased
mean
severity
of
nephropathy;
urinary
bladder
mucosal
hyperplasia,
acute
inflammation
and
polymorph
exudate;
and
ureteral
calculus/
microcalculus,
dilatation,
inflammation,
mucosal
hyperplasia,
squamos
metaplasia,
and
erosion.
Microscopic
calculi/
microcalculi
in
the
urethra
or
kidney
at
5000
ppm
of
two
males
were
considered
treatment
related.
Increased
mineralization
in
several
tissues,
diffuse
parathyroid
hyperplasia,
femoral
and
sternal
fibrous
osteodystrophy,
and
pyloric
stomach
erosions
in
females
at
5000
and
20,000
ppm
were
considered
to
be
secondary
to
nphropathy.
Chronic
toxicity
was
demonstrated
at
dietary
concentrations
of
5000
and
20,0000
ppm.
(
Chronic
toxicity
NOEL
=
500
ppm
(
24.4
mg/
kg/
day
males
and
30.4
mg/
kg/
day
females).
A
urinary
bladder
transitional
cell
carcinoma
and
urinary
bladder
transitional
cell
papilloma
in
two
females
at
5000
ppm
were
considered
treatment
related,
but
secondary
reactive
effects
to
urinary
system
calculi.
(
Oncogenic
effects
NOEL
=
5000
ppm
for
males
(
244.2
mg/
kg/
day),
and
500
ppm
for
females
(
30.4
mg/
kg/
day)).

6.
Animal
metabolism.
Four
groups
of
Sprague­
Dawley
rats,
two
low
dose
groups
of
10
mg/
kg
via
single
oral
and
single
intravenous
injection,
and
two
groups
high
oral
dose
of
1000
mg/
kg
via
single
oral
and
repeat
14­
day
oral.
Sulfosulfuron
and
its
metabolites
were
readily
excreted,
with
urinary
excretion
being
the
major
route
of
elimination
at
low
dose
and
fecal
excretion
at
high
dose;
no
evidence
of
bio­
retention;
tissue
and
blood
levels
were
negligible
with
no
tissue
exceeding
0.2%
of
dose.
In
low­
dose
groups,
absorption
was
greater
than
90%;
high­
dose
groups,
absorption
was
around
40%.
Metabolism
was
limited,
with
demethylation
and
pryrimidine
ring
hydroxylation
as
major
metabolic
routes;
cleavage
of
the
sulfonylurea
bond
is
a
minor
metabolic
pathway;
expiration
as
carbon
dioxide
or
volatiles
was
insignificant.

7.
Metabolite
toxicology.
Dietary
residues
are
almost
entirely
unmetabolized
sulfosulfuron
and
imidazopyridine­
containing
metabolites
sulfonamide
and
guanidine,
for
which
specific
toxicology
data
is
not
available,
but
structures
do
not
suggest
any
specific
toxicologic
concern
and
the
level
of
dietary
exposure
is
low.
Metabolites
are
not
toxicologically
significant.

8.
Endocrine
disruption.
No
evidence
that
exposure
to
sulfosulfuron
had
any
effect
on
reproduction,
fertility
or
mating
indices,
development
or
maturation
of
embryos,
or
development,
growth
and
survival
of
offspring
in
the
short­
term,
chronic,
reproductive
and
developmental
mammalian,
avian
and
aquatic
studies
conducted.
There
were
no
gross
or
microscopic
pathologic
effects
in
endocrine
organs
or
endocrinesensitive
tissues,
or
in
any
reproductive
organs,
tissues
or
endpoints
that
were
considered
related
to
exposure
to
sulfosulfuron.
With
no
evidence
of
bioaccumulation
and
low
environmental
concentrations,
there
is
negligible
risk
of
endocrine
disruption
in
humans
or
wildlife.

C.
Exposure
and
Risk
Assessment
1.
Dietary
exposure
from
food
and
feed
uses.
Tolerances
have
been
established
(
40
CFR
180.552)
for
the
combined
residues
of
sulfosulfuron
in
or
on
wheat
grain,
forage,
hay,
straw
and
related
milk
and
meat
commodities.
Risk
assessments
were
conducted
using
the
proposed
tolerances
to
assess
dietary
exposures
for
sulfosulfuron
in
food
as
follows:
i.
Acute
exposure
and
risk.
Acute
dietary
risk
assessments
are
performed
for
a
food­
use
pesticide
if
a
toxicological
study
has
indicated
the
possibility
of
an
effect
of
concern
occurring
as
a
result
of
a
one­
day
or
single
exposure.
A
dose
and
endpoint
was
not
selected
for
acute
dietary
risk
assessment
because
there
were
no
effects
attributable
to
a
single
dose
(
exposure)
observed
in
oral
toxicology
studies
including
developmental
toxicity
in
the
rat
and
rabbit
and
an
acute
neurotoxicity
study
in
the
rat;
sulfosulfuron
has
low
acute
oral,
dermal
and
inhalation
toxicity,
it
is
non­
irritating
to
skin
and
slightly
irritating
to
eyes,
and
is
not
a
skin
sensitizer.
This
risk
assessment
is
not
required.

ii.
Chronic
exposure
and
cancer
assessment.
Chronic
and
cancer
dietary
risk
assessments
were
conducted
using
the
Dietary
Exposure
Evaluation
Model
 
Food
Consumption
Intake
Database
(
DEEM­
FCID
 
)
model
(
ver.
2.0),
which
uses
food
consumption
data
from
USDA's
Continuing
Surveys
of
Food
Intakes
by
Individuals
(
CSFII);
1994­
1998
data.
The
chronic
and
cancer
analyses
assumed
tolerance
level
residues,
100%
crop
treated,
and
DEEM
 
default
processing
factors.

EPA
has
classified
sulfosulfuron
as
a
likely
human
carcinogen
based
on,
(
1)
occurrence
of
rare
transitional
cell
papilloma
(
benign
tumors)
and
carcinoma
of
the
urinary
bladder
in
female
rats;
(
2)
occurrence
of
rare
benign
mesenchymal
tumors
of
the
urinary
bladder
in
high
dose
male
as
well
as
renal
adenomas
in
female
and
possibly
male
mice,
and
(
3)
the
relevancy
of
the
observed
tumors
to
human
exposure.
For
its
linear
low­
dose
approach
(
Q1*)
for
human
risk
characterization,
EPA
established
the
unit
risk,
Q1*
(
in
milligrams/
kilograms/
day)
(
mg/
kg/
day)­
1
of
sulfosulfuron,
at
1.03
x
10­
3
(
mg/
kg/
day)­
1
in
human
equivalents,
based
upon
the
male
mouse
urinary
bladder
mesenchymal
tumor
rates.
The
rat
translational
cell
tumors
and
mouse
renal
adenomas
were
not
used
because
of
their
low
incidence.

The
mesenchymal
tumors
of
the
urinary
bladder
in
high
dose
males
were
benign
and
unique
to
Swiss
mice,
with
no
human
counterpart
tumor.
Monsanto
contends,
therefore,
that
these
tumors
should
not
be
considered
with
regard
to
human
cancer
risk
assessment
for
sulfosulfuron.
Other
factors,
such
as
structureactivity
analysis
indicating
that
sulfosulfuron
and
the
anticipated
submoieties
should
not
be
carcinogenic,
the
lack
of
genotoxic
effects
either
in
vivo
or
in
vitro,
and
the
fact
that
as
a
class,
sulfonylurea
chemicals
are
notably
lacking
in
carcinogenic
effects,
suggest
that
these
tumors
are
secondary,
threshold
effects
and
are
not
relevant
to
humans
at
the
anticipated
exposure
levels.
Therefore,
Monsanto
contends
that
a
margin
of
exposure
(
uncertainty
factor)
approach
would
be
more
appropriate
in
assessing
human
exposure
levels
than
using
non­
threshold­
based
models.
Since
the
oncogenic
NOEL
was
24
mg/
kg
bw/
day,
establishment
of
a
reference
dose
at
1%
of
the
NOEL
for
chronic
toxicity
(
0.24
mg/
kg
bw/
day)
would
ensure
that
any
potential
oncogenic
risks
from
dietary
exposure
would
be
negligible,
especially
given
the
extremely
low
residues
of
sulfosulfuron
in
wheat
grain.

Chronic
exposure
estimates
for
all
population
subgroups
were
<
1%
cPAD
of
0.24
mg/
kg
bw/
day,
which
is
less
than
EPA's
level
of
concern.
Lifetime
cancer
risk
for
the
U.
S.
population
has
an
MOE
of
126,894
based
on
the
NOEL
of
24
mg/
kg
bw/
day.
Using
the
linear
low­
dose
approach
(
Q1*),
the
lifetime
cancer
risk
for
the
U.
S.
general
population
is
1.9
x
10­
7,
less
than
EPA's
level
of
concern
for
the
this
sub­
group.

iii.
Anticipated
residue
and
percent
crop
treated
(
PCT)
information.
PCT
information
was
not
used
in
this
assessment.
A
conservative
assessment
utilizing
an
assumption
of
100%
crop
treated
and
100%
tolerance
levels
detected,
were
used
for
the
associated
commodities.

2.
Dietary
exposure
from
drinking
water.
There
is
insufficient
water
monitoring
data
on
sulfosulfuron
to
perform
a
comprehensive
dietary
exposure
analysis
and
risk
assessment
for
sulfosulfuron
in
drinking
water.
Peak
(
acute)
and
annual
average
(
chronic)
surface
water
concentrations
of
sulfosulfuron
following
treatment
to
grass
pastures
were,
therefore,
estimated
using
the
FQPA
Index
Reservoir
Screening
Tool
(
FIRST)
(
version
1.0),
the
EPA
Tier
1
screening
model
for
drinking
water
pesticide
exposure.
FIRST
estimates
the
peak
(
acute)
concentration
of
sulfosulfuron
in
surface
water
to
be
7.982
parts
per
billion
(
ppb)
following
aerial
application
(
worst
case)
of
0.094
lb/
acre,
and
an
annual
average
(
chronic)
concentration
of
1.059
ppb.
The
expected
environmental
concentration
(
EEC)
for
sulfosulfuron
in
ground
water
is
estimated
from
the
SCI­
GROW
model
to
be
0.086
ppb
at
a
use
rate
of
0.094
pound/
acre,
aerobic
soil
halflife
of
32
days
and
a
Koc
of
25
L/
kg.

3.
Non­
dietary
exposure.
There
are,
currently,
no
residential
uses
of
sulfosulfuron
that
would
result
in
residential
exposure.
However,
the
commercial
use
of
sulfosulfuron
on
residential
and
recreational
turf
may
lead
to
post­
application
exposure
in
individuals.
A
cancer
risk
assessment
for
adults
and
children
based
on
post­
application
residential
exposure
was
conducted.

Conservative
post­
application
adult
residential
exposure
values
were
calculated
using
REX
4.0.
A
lifetime
average
daily
dose
(
LADD)
of
6.85
x
10­
5
mg/
kg
bw/
day
was
determined
based
on
14
days
of
exposure
per
year,
35
years
of
exposure
lifetime,
and
a
70­
year
life
expectancy.

It
is
likely
that
toddlers
could
be
exposed
to
sulfosulfuron
from
incidental
ingestion
of
grass,
soil,
or
hand­
to­
mouth
transfer
from
residential
turf;
however,
this
residential
exposure
for
toddlers
is
short­
term
(
no
more
than
30
days)
and
should
not
be
considered
chronic
exposure.
The
average
daily
dose
(
ADD)
was
estimated
to
be
0.00607
mg/
kg
bw/
day,
with
and
annual
average
daily
dose
estimated
to
be
0.00023
mg/
kg
bw/
day.
Since
there
are
no
acute
toxicity
concerns
for
sulfosulfuron,
comparison
of
the
average
daily
dose
to
subchronic
toxicity
endpoint
would
provide
the
most
valuable
risk
assessment.
For
this
purpose,
the
NOAEL
of
370
mg/
kg
bw/
day
from
the
subchronic
rat
study
(
MRID
#
44295750)
is
the
appropriate
toxicity
endpoint.
Comparing
then
the
average
daily
dose
of
6.07
x
10­
3
for
toddler
residential
exposure
to
the
subchronic
NOAEL
of
370
mg/
kg
bw/
day
results
in
a
short­
term
MOE
of
60,956,
well
above
EPA's
level
of
concern
of
100.

4.
Cumulative
effects
from
substances
with
a
common
mechanism
of
toxicity.
Section
408(
b)(
2)(
D)(
v)
of
the
FFDCA
requires
that,
when
considering
whether
to
establish,
modify,
or
revoke
a
tolerance,
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."
There
is
no
evidence
of
a
common
mechanism
of
toxicity
finding
as
to
sulfosulfuron,
and
sulfosulfuron
does
not
appear
to
produce
a
toxic
metabolite
that
is
also
produced
by
other
substances.

C.
Safety
Factor
for
Infants
and
Children
1.
In
general.
Section
408
of
the
FFDCA
provides
that
EPA
shall
apply
an
additional
tenfold
margin
of
safety
for
infants
and
children
in
the
case
of
threshold
effects
to
account
for
prenatal
and
postnatal
toxicity
and
the
completeness
of
the
database
on
toxicity
and
exposure
unless
EPA
determines
that
a
different
margin
of
safety
will
be
safe
for
infants
and
children.
Margins
of
safety
are
incorporated
into
EPA
risk
assessments
either
directly
through
use
of
a
MOE
analysis
or
through
using
uncertainty
(
safety)
factors
in
calculating
a
dose
level
that
poses
no
appreciable
risk
to
humans.

2.
Developmental
reproductive
toxicity
studies.
The
results
of
the
two­
generation
reproduction
and
developmental
toxicity
studies
indicated
that
sulfosulfuron
is
not
a
developmental
or
reproductive
toxicant.
The
acute
and
subchronic
neurotoxicity
studies
showed
that
sulfosulfuron
is
not
neurotoxic.
Sulfosulfuron
is
rapidly
excreted,
primarily
unmetabolized.
Excretion
at
low
dose
occurred
primarily
in
the
urine,
whereas,
at
high
dose,
a
large
percentage
of
the
administered
dose
was
excreted
in
the
feces.
Sulfosulfuron
was
not
retained
in
tissues
to
any
significant
extent.

3.
Conclusion.
There
is
a
complete
toxicity
database
for
sulfosulfuron
and
exposure
data
are
complete
or
are
estimated
based
on
data
that
reasonably
accounts
for
potential
exposures.
EPA
has
determined
that
the
10X
safety
factor
to
protect
infants
and
children
should
be
removed.
The
FQPA
factor
is
removed
because
the
developmental
and
reproductive
toxicity
data
did
not
indicate
increased
susceptibility
of
rats
or
rabbits
to
in
utero
and/
or
postnatal
exposure.
Any
detectable
residues
in
food
or
drinking
water
would
be
expected
at
low
levels
since
application
rates
are
low.
There
are
currently
no
registered
homeowner
uses
for
sulfosulfuron.
Finally,
concern
for
post­
application
exposure
to
infants
and
children
from
commercial
application
of
pesticide
is
tempered
by
the
low
acute
oral,
dermal,
and
inhalation
toxicity
of
this
product.

D.
Aggregate
Risks
and
Determination
of
Safety
for
U.
S.
Population
i.
Acute
risk.
As
discussed
previously,
sulfosulfuron
has
low
acute
oral,
dermal,
and
inhalation
toxicity.
It
is
non­
irritating
to
skin,
slightly
irritating
to
eyes
and
is
not
a
skin
sensitizer.
Endpoints
for
risk
assessment
through
exposure
via
the
acute
dietary,
dermal,
inhalation
and
incidental
oral
routes
were
not
identified;
therefore,
acute,
short­
and
intermediate­
term
dermal
and
inhalation
risk
are
not
a
concern.
ii.
Chronic
risk.
Since
exposure
from
dietary
sources
represents
less
than
1%
of
the
cPAD
of
0.24
mg/
kg
bw/
day
for
all
population
subgroups,
including
infants
and
children,
young
children,
young
adults,
females
of
childbearing
age
and
for
the
overall
U.
S.
population,
and
since
chronic
residential
exposure
to
residues
of
sulfosulfuron
in
not
expected
to
occur,
the
DWLOC's
for
sulfosulfuron
may
be
calculated
from
a
maximum
chronic
(
non­
cancer)
water
exposure
equivalent
to
the
cPAD.
DWLOC's
of
8,400
ppb,
7,200
ppb,
and
2,400
ppb,
were
calculated
for
adult
males,
adult
females
and
children,
respectively.
These
values
far
exceed
the
expected
EEC's
of
1.059
ppb
in
surface
water
and
0.086
ppb
in
ground
water,
and,
therefore,
are
not
of
concern.

iii.
Short­
term
risk.
The
short­
term
aggregate
risk
takes
into
account
the
exposure
from
potential
residential
sources
in
addition
to
average
dietary
residues
from
food
and
drinking
water.
The
short­
term
aggregate
risk
assessment
was
performed
for
children,
with
the
resulting
short­
term
DWLOC
of
3,700
ppb
far
greater
than
the
EEC's
for
sulfosulfuron.

iv.
Intermediate­
term
risk.
Intermediate­
term
aggregate
exposure
takes
into
account
non­
dietary,
nonoccupational
exposure
plus
chronic
exposure
to
food
and
water
(
considered
to
be
a
background
exposure
level).
Although
residential
exposure
could
occur
with
the
use
of
sulfosulfuron,
no
toxicological
effects
have
been
identified
for
intermediate­
term
toxicity.
Therefore,
the
aggregate
risk
is
the
sum
of
the
risk
from
food
and
water,
which
were
previously
discussed.

v.
Aggregate
cancer
risk
for
U.
S.
population.
Cancer
aggregate
risk
assessment
considers
exposure
from
food,
water
and
residential
sources.
The
dietary
analysis
assumed
tolerance
level
residues
in
wheat
commodities,
and
milk
and
animal
products,
100%
crop
treated,
and
DEEM
default
processing
factors.
Dietary
exposure
for
the
U.
S.
population
is
0.000189
mg/
kg
bw/
day,
resulting
in
a
lifetime
cancer
risk
MOE
of
126,894,
well
above
EPA's
level
of
concern.
Using
the
linear
Q*
approach,
the
lifetime
excess
cancer
risk
is
1.94
x
10­
7,
less
than
EPA's
level
of
concern.
The
LADD
for
residential
exposure
is
0.0000685
mg/
kg
bw/
day,
resulting
in
a
lifetime
cancer
risk
MOE
of
350,365,
or
an
excess
cancer
risk
of
7.06
x
10­
8
using
the
linear
Q*
approach.
These
values
do
not
exceed
the
EPA's
level
of
concern.
The
aggregate
cancer
risk
DWLOC
for
the
general
population
using
the
MOE
method
is
the
same
as
discussed
previously
for
chronic
(
non­
cancer)
risk,
or
8,200
ppb.
Using
the
linear
Q*
approach,
the
aggregate
cancer
risk
DWLOC
after
combining
the
dietary
and
residential
exposure
is
25
ppb.
These
drinking
water
concentrations
are
much
greater
than
the
expected
concentrations
determined
for
sulfosulfuron
in
ground
and
surface
water.

vi.
Determination
of
safety.
Based
on
these
risk
assessments,
it
is
concluded
that
there
is
a
reasonable
certainty
that
no
harm
will
result
to
the
general
population,
and
to
infants
and
children
from
aggregate
exposure
to
sulfosulfuron
residues.

F.
International
Tolerances.

There
is
neither
a
Codex
proposal,
nor
Canadian
or
Mexican.