OVERVIEW
OF
PRONAMIDE
(Propyzamide)
RISK
ASSESSMENT
Introduction
The
Agency
has
completed
its
review
of
the
available
data
for
the
herbicide
pronamide
and
is
announcing
its
tolerance
reassessment
decision.
This
document
summarizes
EPA's
human
health
findings
and
conclusions
as
presented
fully
in
the
documents
entitled
"Pronamide
Tolerance
Reassessment
Eligibility
Decision
(TRED)"
dated
March
8,
2002,
"Pronamide
Revised
Aggregate
Risk
Estimates
Addendum
to
EPA
March
8,
2002"
dated
May
21,
2002
and
related
documents
supporting
this
decision.
The
purpose
of
this
overview
is
to
assist
the
reader
by
identifying
the
key
features
and
findings
of
the
risk
assessment
in
order
to
enhance
understanding
of
the
conclusions
reached
in
the
tolerance
reassessment
decision.
The
Agency's
reassessment
of
aggregate
risk,
including
exposure
through
food,
drinking
water,
and
residential
exposure
is
required
by
the
Federal
Food,
Drug,
and
Cosmetic
Act
(FFDCA).
The
Agency
must
review
tolerances
and
tolerance
exemptions
that
were
in
effect
when
the
Food
Quality
Protection
Act
(FQPA)
was
enacted
in
August
1996
to
ensure
that
these
existing
pesticide
residue
limits
for
food
and
feed
commodities
meet
the
safety
standard
of
the
new
law.

FFDCA
requires
the
Agency
to
review
all
the
tolerances
for
registered
chemicals
in
effect
on
or
before
the
date
of
the
enactment
of
FQPA.
In
reviewing
these
tolerances,
the
Agency
must
consider,
among
other
things,
aggregate
risks
from
non­
occupational
sources
of
pesticide
exposure,
whether
there
is
increased
susceptibility
to
infants
and
children,
and
the
cumulative
effects
of
pesticides
with
a
common
mechanism
of
toxicity.
The
tolerances
are
considered
reassessed
once
the
safety
finding
has
been
made
or
a
tolerance
revocation
occurs.
A
RED
for
pronamide
was
issued
in
May
1994,
prior
to
enactment
of
FQPA;
therefore
it
needed
to
be
updated
to
consider
the
provisions
of
the
Act.

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

The
risk
assessment
and
documents
pertaining
to
the
Agency's
report
on
FQPA
tolerance
reassessment
progress
and
risk
management
decision
for
pronamide
are
available
on
the
Internet
at
http://
www.
epa.
gov/
pesticides/
reregistration/
status.
htm
and
in
the
public
docket.
The
Agency's
report
on
FQPA
tolerance
reassessment
progress
and
risk
management
decision
for
pronamide
will
be
announced
in
the
Federal
Register.
­2­
Use
Profile
Herbicide:
Pronamide
is
a
selective,
pre­
emergence
herbicide
registered
for
the
control
of
grassy
and
broadleaf
weeds
on
terrestrial
food
crops
[artichoke,
blackberry,
blueberry,
boysenberry,
cherry,
endive
(escarole),
lettuce,
nectarine,
peach,
pear,
plum,
prune,
raspberry,
(black,
red),
rhubarb];
terrestrial
food
and
feed
crops
(agricultural
fallow/
idleland,
apples,
grapes,
peas,
sugar
beets);
terrestrial
non­
food
crops
(Christmas
trees,
clover
plantations,
golf
course
turf,
ornamental
herbaceous
plants,
recreation
area
lawns)
and
outdoor
residential
areas
(ornamental
and/
or
shade
trees,
ornamental
woody
shrubs
and
vines).

Formulations:
Wettable
powder
50%
and
51%
active
ingredient
(a.
i.)
and
technical
grade
92%
a.
i.

Methods
and
Rates
of
Application:
Pronamide
is
produced
and
formulated
for
use
as
a
50
WP
wettable
powder
which
is
packaged
in
water
soluble
pouches
and
then
mixed
in
water
before
application.
Pronamide
is
applied
as
a
liquid
spray.
It
is
a
soil
active
systemic
herbicide
with
uptake
by
susceptible
weeds
occurring
through
the
roots.
Application
rates
range
from
0.5
to
4
lbs
a.
i.
per
acre
per
application
per
year.
Most
crop
sites
have
only
one
application
per
year.
However,
artichokes
have
2
applications
per
year
(at
2
lbs
per
application)
and
gladiolas
have
4
applications
per
year
(at
2
lbs
per
application,
up
to
8
lbs
a.
i.
per
acre
per
application
could
be
applied).
It
is
applied
to
various
food/
feed
crops
using
ground
spray
equipment,
by
hand­
held
sprayer,
soil
incorporation,
or
by
aircraft.

Use
Summary:
Based
on
available
pesticide
usage
data
for
1991
through
2001,
total
annual
domestic
usage
of
pronamide
is
approximately
225,000
pounds.
In
terms
of
pounds
a.
i.,
total
usage
is
allocated
mainly
to
head
lettuce
(29%),
other
lettuce
(19%),
seed
crops
(13%),
fallow
land
(11%),
hay
(other
than
alfalfa)
(8%),
horticulture
(3%)
and
alfalfa
(3%).
Sites
with
5%
or
more
of
acreage
treated
include
lettuce
(other
than
head)
(49%),
head
lettuce
(36%),
California
endive/
escarole
(31%),
artichokes
(21%),
blackberries
(6%)
and
raspberries
(5%).
States
with
significant
usage
in
terms
of
pound
a.
i.
include
Arizona,
California,
Oregon
and
Washington.
Pre­
harvest
intervals,
where
specified,
are
generally
long,
ranging
from
25
to
180
days.

Classification:
Pronamide
is
a
restricted
use
pesticide.

Registrant:
Dow
AgroSciences
(recently
purchased
from
Rohm
and
Haas).
­3­
Human
Health
Risk
Assessment
Acute
Dietary
(Food)
Risk
(For
a
complete
discussion,
see
section
4.2
of
the
Human
Health
Risk
Assessment)

No
toxicologic
endpoint
was
identified
as
appropriate
from
a
single
(acute)
dose
of
pronamide.
Consequently
an
acute
dietary
risk
assessment
was
not
performed
for
pronamide.

Chronic
Dietary
(Food)
Risk
(For
a
complete
discussion,
see
section
4.2
of
the
Human
Health
Risk
Assessment
Chronic
dietary
risk
is
calculated
by
using
the
average
consumption
value
for
food
and
average
residue
values
on
those
foods
over
a
70­
year
lifetime.
A
risk
estimate
that
is
less
than
100%
of
the
chronic
population
adjusted
dose
(cPAD)
(the
dose
at
which
an
individual
could
be
exposed
over
the
course
of
a
lifetime
and
no
adverse
health
effects
would
be
expected)
is
not
of
concern.
The
cPAD
is
the
chronic
reference
dose
(cRfD)
adjusted
for
the
FQPA
Safety
Factor.

The
assessment
showed
that
the
chronic
dietary
risk
estimates
are
not
of
concern,
<1%
of
the
cPAD,
for
the
U.
S.
population
and
for
all
subgroups.

°
The
toxicity
endpoint
for
the
chronic
dietary
assessment
is
based
on
increased
relative
liver
weight
and
non­
neoplastic
histological
changes
in
the
liver,
thyroid,
and
ovaries
in
a
combined
chronic
toxicity/
carcinogenicity
study
in
the
rat.
The
no
observable
adverse
effect
level
(NOAEL)
is
8.46
mg/
kg/
day.
The
lowest
observed
adverse
effect
level
(LOAEL)
is
42.6
mg/
kg/
day.

°
The
Uncertainty
Factor
(UF)
is
100X;
10X
for
intraspecies
variation
and
10X
for
interspecies
extrapolation.

°
The
10x
FQPA
Safety
Factor
was
reduced
to
3x
for
the
following
reasons:

1.
The
toxicological
database
is
adequate
for
FQPA
assessment.
2.
There
was
no
quantitative
or
qualitative
evidence
of
increased
susceptibility
of
rabbits
to
in
utero
exposure
or
to
rats
following
pre/
postnatal
exposure.
Although
the
developmental
toxicity
study,
was
unacceptable
because
a
definitive
NOAEL
as
well
as
a
LOAEL
were
not
established,
no
increased
susceptibility
was
seen
at
the
highest
dose
tested.
3.
A
developmental
neurotoxicity
study
is
not
required.
4.
The
dietary
(food
and
drinking
water)
and
residential
exposure
assessments
will
not
underestimate
the
potential
exposures
for
infants
and
children.
5.
A
3x
was
retained
because
of
evidence
of
endocrine
organ
toxicity
in
the
thyroid,
testes,
ovaries,
adrenal
glands,
pituitary
gland,
thymus.
­4­
For
a
more
complete
discussion
see
the
December
3,
2001
FQPA
Safety
Factor
Committee
report
and
section
5.6
of
the
Pronamide
(Propyzamide):
Report
of
the
Hazard
Identification
Assessment
Review
Committee
(HIARC)
Meeting
for
the
Herbicide,
Pronamide.

°
The
Dietary
Exposure
Evaluation
Model
(DEEM)
was
used
to
estimate
chronic
dietary
exposure.
A
refined
Tier
3
analysis
was
performed
using:
1)
percent
crop
treated;
2)
anticipated
residues
for
meat,
milk,
poultry
and
eggs;
3)
FDA
and
PDP
monitoring
data;
and,
4)
tolerance
level
residues
for
4
crops.

°
The
cPAD
is
0.03
mg/
kg/
day
(chronic
RfD
0.08
mg/
kg/
day
÷
3x
FQPA
safety
factor).

Cancer
Dietary
Risk
(Food)

(For
a
complete
discussion,
see
section
4.2
of
the
Human
Health
Risk
Assessment)

The
cancer
risk
is
calculated
by
using
the
average
consumption
value
for
food
and
average
residue
values
on
those
foods
over
a
70­
year
lifetime.
The
chronic
exposure
value
is
typically
combined
with
a
linear,
low­
dose
approach
(Q1
(
)
to
determine
the
lifetime
(cancer)
risk
estimate.
The
Agency
generally
considers
risks
greater
than
1x10
­6
(i.
e.,
greater
than
one
in
a
million)
not
of
concern.

°
Pronamide
was
previously
classified
as
a
Group
B2
chemical,
probable
human
carcinogen,
based
on
thyroid
follicular
cell
adenomas
(males
and
females)
and
benign
testicular
interstitial
cell
tumors
(males)
in
rats
and
hepatocellular
carcinomas
in
male
mice.

°
A
linear,
low
dose
approach
(Q1
(
)
is
used
for
human
risk
characterization.
The
cancer
potency
unit
risk
(Q1
(
)
based
on
male
mouse
liver
adenoma
and/
or
carcinoma
combined
tumor
rates
is
2.59x10
­2
(mg/
kg/
day)
­1
in
human
equivalents
[converted
from
animals
to
humans
by
use
of
the
(mg/
kg
body
weight)
¾
interspecies
scaling
factor].

°
The
cancer
food
risk
estimate
is
1.06x10
­7
for
the
U.
S.
population,
and
does
not
exceed
the
Agency's
level
of
concern
(1.0x10
­6
or
one
in
one
million).

Residential
Risk
(For
a
complete
discussion,
see
section
4.4
of
the
Human
Health
Risk
Assessment)

As
a
result
of
risk
concerns
for
children
identified
in
the
March
8,
2002
risk
assessment,
the
registrant
agreed
to
voluntarily
cancel
a
product
labeled
for
the
residential
use
(EPA
Reg.
No.
8660­
85;
see
67
FR
13627).
Additionally,
the
registrant
agreed
to
further
limit
use
to
turf
grown
for
seed
or
sod
and
non­
residential
sites
including
golf
courses,
industrial
and
office
building
sites,
stadium
fields
or
professional
athletic
fields.
These
risk
mitigation
measures
­5­
make
children's
non­
dietary
exposure
unlikely.
To
minimize
adult
residential
exposure
related
to
the
sites
listed
above,
the
registrant
has
agreed
to
amend
pronamide
labels
to
require
24
hour
restricted
entry
interval
or
require
watering­
in
as
soon
as
possible
after
application.

Given
these
proposed
restrictions
on
the
use
of
pronamide
on
turf,
high
contact
dermal
scenarios
are
not
likely
to
occur.
Therefore,
the
sole
exposure
scenario
for
the
residential
risk
assessment
is
based
on
low
contact
activity
which
is
represented
and
estimated
by
golf
course
reentry.
The
route
of
exposure
is
dermal.
The
population
at
risk
is
adults.

The
dermal
exposure
estimates
are
considered
somewhat
refined,
since
turf
transferrable
residue
(TTR)
data
from
a
pronamide
TTR
field
study
was
used.
However,
both
the
short­
term
exposure
estimates
and
the
cancer
risk
estimates
relied
on
a
100%
dermal
absorption
factor,
which
results
in
high­
end
dose
estimates.
Therefore,
a
dermal
absorption
study
would
help
to
reduce
these
risk
estimates.

A
3x
FQPA
Safety
Factor
is
required
for
all
population
subgroups
when
assessing
residential
exposures
of
all
durations.
The
rationale
for
reducing
the
safety
factor
is
the
same
as
listed
under
the
chronic
dietary
risk
discussion.

Short­
Term
C
For
short
term
(1­
30)
incidental
oral
exposures
an
adjusted
dose
of
8.46
mg/
kg/
day
was
established
for
use
in
the
risk
assessment.
This
dose
is
derived
from
the
NOAEL
from
a
chronic
toxicity/
carcinogenicity
study
in
rats,
where
the
effects
are
increased
liver
weight
and
non­
neoplastic
histologic
changes
in
the
liver,
thyroid,
and
ovaries
observed
at
the
LOAEL
of
42.6
mg/
kg/
day.
The
dose
selection
is
based
on
a
maternal
toxicity
NOAEL
of
5
mg/
kg/
day
and
clinical
signs
of
toxicity
(soiled
anal
area
and
anorexia)
and
liver
effect
(punctate
vacuolation
of
hepatocytes)
observed
at
the
LOAEL
of
20
mg/
kg/
day
in
the
developmental
toxicity
study
conducted
in
rabbits.
Although
this
study
is
of
the
appropriate
route
(oral)
and
duration
(13
days),
the
NOAEL
(5
mg/
kg/
day)
in
this
study
is
lower
than
the
NOAEL
(8.46
mg/
kg/
day)
established
in
the
chronic
toxicity/
carcinogenicity
study
in
the
rat.
The
apparent
disparity
between
these
NOAELs
is
driven
by
the
doses
of
pronamide
selected
for
testing
in
these
studies.
The
Agency
concluded
that
using
a
more
realistic
NOAEL
of
8.46
mg/
kg/
day,
rather
than
5
mg/
kg/
day,
would
provide
a
sufficiently
protective
dose
for
risk
assessment.

°
The
short­
term
dermal
endpoint
has
a
10x
UF
for
intraspecies
variability
and
10x
UF
for
interspecies
extrapolation.
When
considering
the
FQPA
Safety
Factor
of
3x,
MOEs
must
be
$
300
to
be
above
the
Agency's
level
of
concern.

°
The
short­
term
exposure
estimates
are
considered
high­
end
estimates,
since
the
maximum
application
rate
is
used,
a
100%
dermal
absorption
factor
is
assumed
and
exposures
are
assumed
to
occur
on
the
day
of
treatment.
°
The
exposure
scenario
is
based
on
low
contact
activity
golf
course
reentry.
The
route
of
exposure
is
dermal.
The
population
at
risk
are
adults.
­6­
°
The
short­
term
Margin
of
Exposure
(MOE)
for
golf
course
reentry
using
zero
day
after
treatment
(DAT
0)
turf
transferable
residue
data
from
the
turf
study
is
1000.
Therefore,
the
Agency
is
not
concerned
about
short
term
residential
exposure
to
pronamide.

Intermediate­
Term
No
intermediate
or
long
term
exposure
scenarios
(i.
e.,
greater
than
30
days)
are
anticipated
based
on
the
results
of
the
turf
transferable
residue
(TTR)
study
which
showed
that
residues
dissipate
to
below
the
level
of
quantification
by
day
14
following
application.

Cancer­
Risk
°
As
stated
previously,
pronamide
is
classified
as
a
Group
B2
chemical,
probable
human
carcinogen
with
inadequate
evidence
in
humans.

°
The
cancer
potency
(Q1*)
is
2.59
x
10
­2
(mg/
kg/
day)
­1
in
human
equivalents.

°
The
adult
golfer
cancer
risk
is
estimated
at
1.15
x
10
­7
.
In
order
to
exceed
the
cancer
risk
(1.0
x
10
­6
),
an
exposure
frequency
of
8.7
days
per
year
would
be
needed
for
the
activity
of
golf.
Because
pronamide
is
applied
one
time
per
year,
the
Agency
does
not
believe
this
exposure
frequency
will
occur.
Therefore,
the
cancer
risk
for
golfers
does
not
exceed
the
Agency's
level
of
concern.

Drinking
Water
Dietary
Risk
(For
a
complete
discussion,
see
section
4.3
of
the
Human
Health
Risk
Assessment)

Drinking
water
exposure
to
pesticides
can
occur
through
groundwater
and
surface
water
contamination.
EPA
considers
both
acute
(one
day)
and
chronic
(lifetime)
drinking
water
risks
and
uses
either
modeling
or
actual
monitoring
data,
if
available,
to
estimate
those
risks.

°
A
Tier
I
Drinking
Water
Assessment
for
pronamide
was
conducted
using
the
SCI­
GROW
model
for
groundwater.
The
Tier
I
groundwater
estimates
were
predicted
from
application
of
pronamide
at
the
maximum
label
rate
(2
lbs
active
ingredient
per
acre
four
times
per
year)
for
ornamental
herbaceous
plants,
and
represent
upper­
bound
estimates
of
the
concentrations
that
might
be
found
in
groundwater
due
to
the
use
of
pronamide/
propyzamide.
The
resulting
modeled
groundwater
screening
concentration
is
1.1
ppb.

°
The
Tier
II
PRZM­
EXAMS
model
was
used
to
predict
EECs
for
pronamide
in
surface
water.
Conservative
inputs
were
used
for
the
environmental
(soil
and
water
metabolism)
assumptions,
(i.
e.,
2x
and
3x
extrapolation
factors
were
applied
to
soil
and
water
halflives
used
in
the
PRZM­
EXAMS
assessment).
Maximum
label
application
rates
were
­7­
used
for
major
crops.
The
chronic
EEC
values
ranged
from
0.53
to
4.45
ppb
(the
low
end
crop
was
lettuce
in
Florida,
and
the
high
end
crop
was
alfalfa
in
California).
Using
the
36­
year
mean
concentration
values
for
cancer
risk
estimates,
the
average
exposure
values
ranged
from
0.54
to
4.3
ppb.

°
Although
there
is
no
legal
requirement
under
the
Safe
Drinking
Water
Act
to
monitor
for
pronamide,
it
has
been
detected
in
surface
and
groundwater
in
various
locations
in
the
U.
S.
The
maximum
level
detected
was
0.365
ppb
(surface
water)
at
Zollner
Creek
near
Mt.
Abgel,
Oregon
on
Nov.
16,
1998
and
the
range
was
0.0037
to
0.365
ppb
(surface
water)
(USGS
­
NAWQA).
The
maximum
ground
water
detection
was
at
Benton
Ozark,
AK
at
0.82
ppb
on
April
13,
1994,
and
ranging
from
0.005
­
0.82
ppb.

°
Short­
term
and
chronic
drinking
water
exposure
to
pronamide
did
not
result
in
a
risk
estimate
of
concern
for
non­
cancer
risks.
The
short
term
EECs
ranged
between
3.7
to
10.3
ppb,
depending
on
the
crop,
compared
to
the
DWLOC
which
ranged
from
560
to
700
ppb.
The
chronic
non­
cancer
EECs
ranged
between
0.53
to
4.45
ppb,
depending
on
the
crop,
compared
to
the
chronic
DWLOC
which
ranged
between
300
to
1050
ppb.

°
There
are
cancer
risk
estimates
which
slightly
exceed
the
Agency's
level
of
concern.
While
the
modeled
groundwater
EEC
is
1.1
ppb
compared
to
the
cancer
DWLOC
1.06
ppb,
the
modeled
surface
water
EECs
exceed
the
DWLOC
for
some
crops
(the
surface
water
cancer
EECs
range
from
0.54
to
4.3
ppb).

Aggregate
Risk
(For
a
complete
discussion,
see
section
5.0
of
the
Human
Health
Risk
Assessment
and
Addendum
to
EPA
March
8,
2002:
Pronamide.
Tolerance
Reassessment
Eligibility
Decision
(TRED))

FQPA
requires
an
aggregate
risk
assessment
to
be
conducted
considering
all
nonoccupational
sources,
including
exposure
from
water,
food,
and
residential
use.
Because
there
are
potential
exposures
to
treated
turf,
the
aggregate
exposure
assessment
for
pronamide
includes
exposure
estimates
from
residential
sources
as
well
as
food
and
drinking
water.

The
Agency
uses
a
drinking
water
level
of
comparison
(DWLOC)
as
a
surrogate
to
capture
risk
associated
with
exposure
from
pesticides
in
drinking
water.
The
DWLOCs
represent
the
maximum
contribution
to
the
human
diet
(in
ppb
or
:
g/
L)
that
may
be
attributed
to
residues
of
a
pesticide
in
drinking
water
after
dietary
exposure
is
subtracted
from
the
chronic
Population
Adjusted
Dose
(cPAD)
or
cPAD.
Risks
from
drinking
water
are
assessed
by
comparing
the
DWLOCs
to
the
estimated
environmental
concentrations
(EECs)
in
surface
water
and
groundwater.
If
the
EEC
is
less
than
the
DWLOC,
there
is
generally
no
drinking
water
concerns.
The
EECs
for
average
concentrations
of
pronamide
were
based
on
PRZM­
EXAMS
for
surface
water
and
SCI­
GROW
for
groundwater.
Drinking
water
modeling
is
considered
to
be
an
unrefined
assessment
and
provides
high­
end
estimates.
­8­
Short
Term
Risk
The
short­
term
food,
water,
and
low­
contact
dermal
(golfing)
pronamide
exposures
were
aggregated
in
the
Risk
Assessment,
and
the
estimated
environmental
concentration
(EECs)
for
surface
water
(3.69
to
10.3
ppb)
and
ground
water
(1.1
ppb),
modeled
using
SCI­
GROW
and
PRZM­
EXAMS,
did
not
exceed
the
DWLOC
(range
560­
700
ppb).
Therefore,
risk
estimates
for
all
pathways
of
exposure
are
not
of
concern
for
pronamide
short­
term
exposure
when
pronamide
use
is
restricted
per
the
label
changes
cited
above.

Chronic
Risk
Due
to
the
short­
term,
intermittent
nature
of
residential
exposure
to
pronamide,
only
dietary
and
water
intake
were
included
in
the
chronic
aggregate
exposure
estimate.
The
chronic
DWLOC
is
the
concentration
in
drinking
water
as
a
part
of
the
aggregate
chronic
exposure
that
occupies
no
more
than
100%
of
the
cPAD
when
considered
together
with
other
sources
of
exposure.

To
calculate
the
chronic
DWLOC
exposure
relative
to
a
chronic
toxicity
endpoint,
the
chronic
dietary
food
exposure
(from
DEEM™)
was
subtracted
from
the
chronic
PAD
to
obtain
the
acceptable
chronic
exposure
to
pronamide
in
drinking
water.
The
DWLOC
was
calculated
and
compared
to
the
EECs.

°
The
chronic
DWLOCs
(300
­
1050
ppb)
were
greater
than
the
EECs
for
modeled
surface
water
(0.53
­
4.45
ppb),
and
modeled
groundwater
(1.1
ppb).
In
addition,
non­
targeted
USGS
monitoring
data
ranged
from
0.0037
to
0.365
ppb
in
surface
water,
and
from
0.005
­
0.82
ppb
in
ground
water.
The
Agency
concludes
the
chronic
aggregate
risk
estimates
do
not
exceed
the
level
of
concern.

Cancer
Risk
Aggregate
cancer
risk
estimates
will
be
reduced
by
restricting
non­
agricultural
uses
to
turf
for
sod
and
seed,
ornamental
landscaping,
industrial
sites,
professional
athletic
fields,
and
golf
courses.
Golfing
is
believed
to
be
a
representative
scenario
for
likely
exposures
to
the
public.

°
The
cancer
risk
estimate
for
golfing
a
single
day
per
year
is
about
the
same
as
the
dietary
cancer
risk
estimate,
or
1
x
10
­7
.
After
considering
both
dietary
and
non­
dietary
exposure,
the
cancer
DWLOC
is
1.06
ppb.
Without
golf
course
exposure
(i.
e.,
no
recreational
turf
uses
at
all),
the
cancer
DWLOC
would
be
1.2
ppb
based
on
food
exposure
alone.

°
The
Tier
2
PRZM­
EXAMS
36
year
mean
EECs
are
0.535­
4.35
ppb.
The
modeled
groundwater
EEC
using
SCI­
GROW
is
1.1
ppb.
­9­
°
While
the
modeled
EECs
(4.35
ppb)
are
slightly
higher
than
the
cancer
DWLOC
(1.06
ppb),
the
Agency
is
not
concerned
because
of
the
conservative
inputs
used
in
the
surface
water
modeling.
The
PRZM­
EXAMS
assessment
was
based
on
the
maximum
label
rates
for
pronamide,
whereas
typical
rates
for
many
crops
are
25%­
50%
less.
The
model
also
assumed
a
Percent
Crop
Area
(PCA)
of
87%,
which
is
likely
to
be
an
overestimate
for
the
commodities
being
assessed.
In
addition,
pronamide
data
exists
for
only
one
soil
in
the
aerobic
soil
metabolism
study.
When
aerobic
soil
metabolism
data
is
only
available
in
one
soil,
a
conservative
extrapolation
factor
is
used
which
is
likely
to
contribute
to
overestimating
potential
persistence
and
exposure.
As
a
result,
Dow
AgroSciences
has
agreed
to
conduct
an
aerobic
soil
metabolism
study
(two
additional
soils)
and
an
aerobic
aquatic
metabolism
study
as
confirmatory
data.

°
Further
refinement
of
drinking
water
modeling
estimates
and/
or
targeted
monitoring
of
water
sources
in
high
pronamide
use
areas
would
provide
more
confidence
in
the
risk
assessment.
Additionally,
information
concerning
the
behavior
of
pronamide
following
drinking
water
treatment
regimes
would
also
help
refine
exposure
estimates.

Tolerance
Reassessment
Summary
Pronamide
tolerances
are
established
under
40
CFR
§180.317
(a),
(b)
and
(c).
The
tolerance
expression,
listed
in
(a)
and
(c),
is
in
terms
of
the
combined
residues
of
the
herbicide
propyzamide
and
its
metabolites
(containing
the
3,
5­
dichlorobenzoyl
moiety
and
calculated
as
3,
5
dichloro­
N­
(1,1­
dimethyl­
2­
propynyl)
benzamide).
The
tolerance
expression,
listed
in
(b),
is
in
terms
of
the
parent
only.
The
Agency
recommends
that
the
tolerance
expression
under
(b)
be
modified
to
include
the
metabolites.
The
Agency
also
recommends
the
following:
decreasing
the
established
tolerance
for
artichokes;
increasing
the
tolerances
for
cattle
fat,
goat
fat,
hog
fat,
horse
fat,
and
sheep
fat,
revoking
the
tolerance
for
poultry
kidney,
grass,
forage:
and,
proposing
a
tolerance
for
alfalfa
seed.
The
Table
below
summarizes
EPA's
tolerance
reassessment
decision
which
accounts
for
47
tolerance
reassessments.

The
Codex
Commission
has
established
several
maximum
residue
limits
(MRLs)
for
residues
of
pronamide
in/
on
various
raw
agricultural
and
processed
commodities.
The
Codex
MRLs
are
expressed
in
terms
of
pronamide
per
se.
The
Codex
MRLs
and
the
U.
S.
tolerances
will
be
incompatible
when
the
U.
S.
tolerance
expression
for
plant
commodities
is
revised
to
include
residues
of
pronamide
and
the
metabolites.
­10­
Tolerance
Reassessment
Summary
for
Pronamide
Commodity
Established
Tolerance
(ppm)
Reassessed
Tolerance
(ppm)
Comment
Correct
Commodity
definition
Tolerances
Listed
Under
40
CFR
§180.317(
a)
Apples
0.1
0.
1
Artichokes
0.1
0.
01
Residues
of
pronamide
and
its
metabolites
containing
the
3,5­
dichlorobenzoyl
moiety
were
nondetectable
(less
than
the
level
of
concern
(LOC)
of
0.01ppm)
in/
on
each
sample
of
artichokes
harvested
61
days
following
a
single
application
of
a
representative
pronamide
formulation
at
4.0
or
8.0
lb
ai/
A.

Blackberries
0.05
0.05
Blueberries
0.05
0.05
Boysenberries
0.05
0.05
Cattle,
fat
0.02
0.20
Fat
tolerance
raised
due
to
linear
extrapolation
of
maximum
residues
observed
in
fat
at
40
ppm
feeding
level
relative
to
the
Maximum
theoretical
dietary
burdens
(MTDB)

Cattle,
kidney
0.
4
0.4
Cattle,
liver
0.4
0.
4
Cattle,
mbyp
(except
kidney,
liver)
0.
02
0.
02
Cattle,
meat
0.02
0.02
Eggs
0.02
0.02
Endive
(escarole)
1.0
1.
0
Goats,
fat
0.02
0.20
Fat
tolerance
raised
due
to
linear
extrapolation
of
maximum
residues
observed
in
fat
at
40
ppm
feeding
level
relative
to
the
MTDB
Goats,
kidney
0.4
0.
4
Goats,
liver
0.4
0.
4
Goats,
mbyp
(except
kidney,
liver)
0.
02
0.
02
Goats,
meat
0.02
0.02
Grapes
0.1
0.
1
Hogs,
fat
0.
02
0.
20
Fat
tolerance
raised
due
to
linear
extrapolation
of
maximum
residues
observed
in
fat
at
40
ppm
feeding
level
relative
to
the
MTDB
Hogs,
kidney
0.
4
0.4
Hogs,
liver
0.4
0.
4
Hogs,
mbyp
(except
kidney)
0.02
0.02
Hogs,
meat
0.02
0.02
Horses,
fat
0.
02
0.
20
Fat
tolerance
raised
due
to
linear
extrapolation
of
maximum
residues
observed
in
fat
at
40
ppm
feeding
level
relative
to
the
MTDB
Commodity
Established
Tolerance
(ppm)
Reassessed
Tolerance
(ppm)
Comment
Correct
Commodity
definition
­11­
Horses,
kidney
0.
4
0.4
Horses,
liver
0.4
0.
4
Horses,
mbyp
(except
kidney)
0.02
0.02
Horses,
meat
0.02
0.02
Lettuce
1.0
1.
0
Lettuce
Head
Only
head
lettuce
is
supported
by
acceptable
data;
leaf
lettuce
uses
must
be
removed
from
the
label.
Alternatively,
the
label
may
be
revised
to
specify
a
practical
PHI
(35­
day)
for
leaf
lettuce
and
supporting
data
be
submitted.

Milk
0.02
0.02
Non­
grass
animal
feeds
10.0
10.0
Non­
grass
animal
feeds
(forage,
fodder,
straw,
and
hay)
group
Pears
0.
1
0.1
Poultry,
fat
0.
02
0.
02
Poultry,
kidney
0.
2
Revoke
Tolerances
are
typically
not
established
for
poultry
kidneys.

Poultry,
liver
0.2
0.
2
Poultry,
mbyp
(except
kidney,
liver)
0.02
0.02
Poultry,
meat
0.02
0.02
Radicchio,
greens
(tops)
2.
0
2.0
Raspberries
0.05
0.05
Sheep,
fat
0.
02
0.
20
Fat
tolerance
raised
due
to
linear
extrapolation
of
maximum
residues
observed
in
fat
at
40
ppm
feeding
level
relative
to
the
MTDB
Sheep,
kidney
0.
4
0.4
Sheep,
liver
0.4
0.
4
Sheep,
mbyp
(except
kidney,
liver)
0.02
0.02
Sheep,
meat
0.02
0.02
Stone
fruit
0.1
0.
1
Commodity
Established
Tolerance
(ppm)
Reassessed
Tolerance
(ppm)
Comment
Correct
Commodity
definition
­12­
Tolerances
To
Be
Proposed
Under
40
CFR
§180.317(
a)
Alfalfa
Seed
­­
10.0
Tolerance
recommendation
is
contingent
upon
required
label
revision
to
specify
a
50­
day
PHI
and
a
maximum
seasonal
rate
of
2.0
lb
ai/
A
Tolerances
Listed
Under
40
CFR
§180.317(
b)
Cranberries
0.05
­­
Temporary
tolerance
associated
with
a
FIFRA
section
18
that
will
expire
12/
31/
03.
Grass,
forage
1.0
­­
Tolerance
expired
12//
31/
01.
Tolerances
Listed
Under
40
CFR
§180.317(
c)
Peas,
dried
0.
05
TBD
Pea,
field,
seed.
European
data
currently
used
to
support
tolerance.
Registrant
needs
to
submit
field
trial
data
as
confirmatory
data.
Rhubarb
0.1
0.
1
Tolerances
To
Be
Proposed
Under
40
CFR
§180.317(
c)
Pea,
field,
hay
–
TBD
Pea,
field
vines
–
TBD
*TBD=
To
Be
Determined
Summary
of
Pending
Data
Most
pertinent
product
chemistry
data
requirements
are
satisfied
for
technical
grade
active
ingredients.
The
following
information
is
required:

°
Product
Chemistry
GDLN
Description
860.1200
Direction
for
use
860.1380
Storage
Stability
Data
°
Additional
data
are
also
required
for
the
51%
Formulation
Intermediate
(FI)
concerning
the
following:

GDLN
Description
830.6314
oxidation/
reduction
830.6316
explodability
830.6317
storage
stability
830.6320
corrosion
characteristics
­13­
The
registrant
must
either
certify
that
the
supplier
of
beginning
materials
and
the
manufacturing
processes
have
not
changed
since
the
last
comprehensive
product
chemistry
reviews
or
submit
complete
updated
product
chemistry
data
packages.

Although
there
is
confidence
in
the
overall
scientific
quality
of
the
available
toxicity
data,
several
data
gaps
were
identified
which
are
required
to
fulfill
the
OPPTS
harmonized
test
guidelines:

°
Toxicity
GDLN
Description
870.3700
Developmental
study
in
rats
Non
GDLN
Comparative
thyroid
rat
assay
in
adult
animals
and
offspring
870.3200
21­
day
dermal
toxicity
study
Non
GDLN
28­
day
inhalation
study
870.7600
dermal
penetration
study
A
review
of
registered
uses
and
the
supporting
residue
chemistry
data
indicates
the
following
residue
data
are
required:

°
Residue
(GDLN
860.1500
Crop
Field
Trials)

dried
winter
peas
vines
and
hay
of
winter
peas
°
Confirmatory
storage
stability
data
(GDLN
860.1380)
are
required
for
regulated
pronamide
metabolites
on
the
following:

alfalfa
apples
grapes
lettuce
peaches
plums
°
A
confirmatory
aerobic
soil
metabolism
study
(835.4100)
and
an
aerobic
aquatic
metabolism
study
(835.4300)
are
required.

The
registrant
is
required
to
further
optimize/
improve
the
revised
animal
enforcement
method
(TR
34­
91­
68)
to
yield
acceptable
recoveries
at
a
fortification
level
equal
to
established
animal
tolerances.
Following
method
improvement,
the
registrant
is
required
to
submit
bridging
independent
laboratory
validation
(ILV)
data;
the
required
ILV
data
should
include
two
control
samples
fortified
at
0.4
ppm,
the
reassessed
tolerance
level
for
the
kidney
and
liver
of
ruminants.
­14­
°
The
following
label
amendments
are
required
for
lettuce,
peas,
and
alfalfa
grown
for
seed:

GDLN
Description
860.1850
Confined
Accumulation
in
Rotational
Crops
860.1900
Field
Accumulation
in
Rotational
Crops
°
30­
day
plant­
back
interval
for
leafy
vegetables
(except
Brassica
vegetables)
°
90­
day
plant­
back
interval
for
root
and
tuber
vegetables
°
360­
day
plant­
back
interval
for
cereal
grains,
forage
and
fodder,
and
straw
of
cereal
grain
