Document ID: EPA-HQ-OPP-2002-0159-0011
Agency: epa
Document Type: Supporting & Related Material
Title: 
Posted Date: 2002-07-12T04:00Z

UNITED
STATES
ENVIRONMENTAL
PROTECTION
AGENCY
WASHINGTON,
D.
C.
20460
OFFICE
OF
PREVENTION,
PESTICIDES
AND
TOXIC
SUBSTANCES
July
5,
2002
CERTIFIED
MAIL
Dear
Registrant:

This
is
the
Environmental
Protection
Agency's
(hereafter
referred
to
as
EPA
or
the
Agency)
"Report
of
FQPA
Tolerance
Reassessment
Progress
and
Interim
Risk
Management
Decision"
(TRED)
for
pronamide
that
was
completed
on
July
5,
2002.
A
Notice
of
Availability,
soliciting
public
comment
for
a
30
day
period,
will
be
published
in
the
Federal
Register
(FR)
shortly.

The
Federal
Food
Drug
and
Cosmetic
Act
(FFDCA),
as
amended,
requires
EPA
to
reassess
all
the
tolerances
for
registered
chemicals
in
effect
on
or
before
the
date
of
the
enactment
of
the
Food
Quality
Protection
Act
(FQPA)
in
August
of
1996
against
the
new
safety
standard
adopted
in
the
FQPA.
In
reassessing
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
modification
or
revocation
occurs.
A
reregistration
eligibility
decision
(RED)
for
pronamide,
was
completed
May
1994,
prior
to
FQPA
enactment.
Therefore,
it
needed
to
be
updated
to
reassess
the
tolerances
under
the
FQPA
standard.

The
Agency
has
evaluated
the
dietary
risk
associated
with
pronamide
and
has
determined
that,
provided
the
risk
mitigation
measures
outlined
in
this
document
are
implemented,
there
is
a
reasonable
certainty
that
no
harm
to
any
population
subgroup
will
result
from
aggregate
exposure
to
pronamide
when
considering
dietary
exposure
and
all
other
non­
occupational
sources
of
pesticide
exposure
for
which
there
is
reliable
information.
Therefore,
the
tolerances
established
for
residues
of
pronamide
in/
on
raw
agricultural
commodities
are
now
considered
reassessed
as
safe
under
section
408(
q)
of
the
FFDCA.

FQPA
requires
that
EPA
consider
"available
information"
concerning
the
cumulative
effects
of
a
particular
pesticide's
residues
and
"other
substances
that
have
a
common
mechanism
of
toxicity."
The
reason
for
consideration
of
other
substances
is
due
to
the
possibility
that
lowlevel
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.
­2­
EPA
did
not
perform
a
cumulative
risk
assessment
as
part
of
this
tolerance
reassessment
review
of
pronamide,
because
the
Agency
has
not
determined
if
there
are
any
other
chemical
substances
that
have
a
mechanism
of
toxicity
common
with
that
of
pronamide.
If
EPA
identifies
other
substances
that
share
a
common
mechanism
of
toxicity
with
pronamide,
then
a
cumulative
risk
assessment
will
be
conducted
that
includes
pronamide
once
the
final
framework
EPA
will
use
for
conducting
cumulative
risk
assessments
is
available.
Further,
EPA
is
in
the
process
of
developing
criteria
for
characterizing
and
testing
endocrine
disrupting
chemicals
and
plans
to
implement
an
Endocrine
Disruptor
Screening
Program.
Pronamide
will
be
reevaluated
at
that
time
and
additional
studies
may
be
required.

The
Agency's
human
health
findings
for
the
pesticide
pronamide,
were
discussed
in
a
closure
conference
call
held
on
June
28,
2002,
and
are
summarized
in
the
attached
chemical
overview
of
the
risk
assessments.
These
risk
assessments
and
other
documents
pertaining
to
the
pronamide
tolerance
reassessment
decision
are
listed
at
the
end
of
this
document
and
are
available
on
the
Internet
at
http://
www.
epa.
gov/
pesticides/
reregistration/
status.
htm
and
in
the
public
docket
for
viewing.

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:

C
Decreasing
the
established
tolerance
for
artichokes;
C
Increasing
the
tolerances
for
cattle
fat,
goat
fat,
hog
fat,
horses
fat,
and
sheep
fat;
C
Revoking
the
tolerance
for
poultry
kidney
and
grass,
forage;
and,
C
Proposing
a
tolerance
for
alfalfa
seed
and
pea
vines
and
hay.

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.
­3­
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
­4­
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
­5­
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
Risk
Mitigation:

As
a
result
of
risk
concerns
for
children
identified
in
the
March
8,
2002
risk
assessment,
Dow
AgroSciences
agreed
to
voluntarily
cancel
all
product
labeled
for
residential
use
(EPA
Reg.
No.
8660­
85;
see
67
FR
13627).
Additionally,
in
order
to
further
address
this
risk
concern
and
minimize
the
likelihood
of
non­
dietary
exposure
to
children,
the
following
label
statement
must
appear
on
Pronamide
end­
use
products:

"This
product
may
only
be
used
on
turf
grown
for
seed
or
sod
or
on
nonresidential
sites
including
golf
course,
industrial
and
office
building
sites,
stadium
fields
or
professional
athletic
fields."

To
minimize
adult
non­
occupational
exposure,
the
following
label
statement
must
appear
on
Pronamide
end­
use
products:

"For
all
uses
except
those
specified
below,
do
not
enter
or
allow
others
to
enter
until
sprays
have
dried.
When
applied
to
stadium
or
professional
athletic
fields,
water­
in
immediately
after
application
or,
do
not
enter
or
allow
others
to
enter
treated
area
for
24­
hours
after
application.
If
product
is
watered­
in
after
treatment,
do
not
enter
or
allow
other
persons
to
enter
until
area
had
dried"
­6­
The
risk
assessment
also
identified
a
slight
cancer
risk
due
to
pronamide
exposure
in
drinking
water
from
surface
water
sources
(EECs
are
4.3
ppb
compared
to
the
cancer
DWLOC
of
1.1
ppb).
However,
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
crops
being
considered.
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
over­
estimating
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.

The
Agency
will
be
issuing
a
generic
Data
Call­
In
(DCI)
that
outlines
further
data
requirements
for
this
chemical.
The
following
additional
data
are
required
for
pronamide.
The
registrants
of
pronamide
must
respond
within
90
days
of
receipt
of
this
letter
from
the
Agency.

Most
pertinent
product
chemistry
data
requirements
are
satisfied
for
technical
grade
active
ingredients.
The
following
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
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.
­7­
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.
­8­
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
If
you
have
questions
on
this
document,
please
contact
the
Chemical
Review
Manager,
Cecelia
Watson,
at
(703)
305­
4329.
For
questions
regarding
label
changes
and
registration
action,
please
contact
Jim
Tompkins
of
the
Registration
Division
at
(703)
305­
5697.

Sincerely,

Lois
A.
Rossi,
Director
Special
Review
and
Reregistration
Division
Enclosures:

C
Overview
and
Summary
of
Pronamide
(Propyzamide)
Risk
Assessment
C
Hazard
Identification
Assessment
Review
Committee
(HIARC)
report
(M.
Centra,
December
10,
2001)
C
Report
of
the
FQPA
Safety
Factor
Committee
(C.
Christensen,
December
19,
2001)
C
Toxicology
Chapter
of
the
Tolerance
Reassessment
Eligibility
Decision
(TRED)
(M.
Centra,
March
7,
2002)
C
Report
of
the
Mechanism
of
Toxicity
Assessment
Review
Committee
(MTARC)
(M.
Centra,
January
21,
2001)
C
Review
of
Pronamide
Incident
Reports
(
J.
Blondell
&
M..
Spann,
August
12,
2001)
C
Chronic
and
Cancer
Dietary
Exposure
Assessments
(D.
Soderberg,
et
al.,
February
7,
2002)
C
Pronamide
Residue
Chemistry
chapter
(J.
Morales,
February
28,
2002)
C
Residential
Risk
Assessment,
(B.
O'Keefe,
March
7,
2002)
C
Drinking
Water
Assessment
to
Support
TRED
for
Propyzamide
(Pronamide)
(L.
Shanaman,
May
16,
2001)
C
Addendum
to
EPA
March
8,
2002:
Pronamide.
Tolerance
Reassessment
Eligibility
Decision
(TRED).
(G.
Bangs
May
21,
2002)
C
Tier
II
Water
Assessment
to
Support
TRED
for
Pronamide
(Propyzamide)
(L.
Shanaman,
May
31,
2002).