TXR
NO.
0050361
December
19,
2001
MEMORANDUM
SUBJECT:
PRONAMIDE­
Report
of
the
FQPA
Safety
Factor
Committee
FROM:
Carol
Christensen,
Acting
Executive
Secretary
FQPA
Safety
Factor
Committee
Health
Effects
Division
(7509C)

THROUGH:
Ed
Zager,
Chair
FQPA
Safety
Factor
Committee
Health
Effects
Division
(7509C)

TO:
Jose
Morales,
Risk
Assessor
Reregistration
Branch
III
Health
Effects
Division
(7509C)

PC
Code:
101701
The
FQPA
Safety
Factor
Committee
evaluated
the
available
hazard
and
exposure
data
for
pronamide
on
December
3
rd
,
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
could
be
reduced
(3x)
in
assessing
the
risk
posed
by
this
chemical.
2
I.
HAZARD
ASSESSMENT
(Memorandum:
Michelle
Centra
to
Carol
Christensen,
dated
November
26,
2001)

A.
Adequacy
of
the
Toxicology
Database
The
toxicology
data
base
for
pronamide
is
adequate
for
FQPA
assessment.
The
toxicology
data
base
for
pronamide
was
reviewed
by
the
Hazard
Identification
Assessment
Review
Committee
(HIARC)
on
November
6
th
,
2001.
Prenatal
developmental
toxicity
studies
in
the
rabbit
and
a
two­
generation
reproduction
study
are
available
with
pronamide.
However,
the
submitted
prenatal
developmental
toxicity
study
in
rats
was
evaluated
and
classified
as
unacceptable­
guideline
(not
upgradeable).
Neither
a
LOAEL
nor
a
definitive
NOAEL
was
established
in
this
study,
and,
no
toxicities
were
observed
in
the
maternal
animals
and
their
fetuses.

B.
Determination
of
Susceptibility
The
results
of
the
available
developmental
toxicity
study
in
rabbits
and
two­
generation
reproduction
study
in
rats
indicated
no
susceptibility
to
the
fetuses
of
rabbits
or
to
the
offspring
of
rats
following
pre­
and/
or
postnatal
exposure
to
pronamide.
Fetal/
offspring
effects
in
both
the
rat
and
rabbit
were
observed
at
either
the
same
or
higher
dose
levels
which
produced
maternal/
parental
toxicity.

C.
Requirement
of
a
Developmental
Neurotoxicity
Study
The
HIARC
determined
that
a
developmental
neurotoxicity
study
in
rats
is
not
required.
However,
endocrine
effects
(thyroid,
testes,
ovaries,
adrenal
glands,
pituitary
gland,
thymus)
were
identified
in
the
majority
of
studies
conducted
across
species.
Since
thyroid
hormone
disruptions
are
known
to
be
associated
with
adverse
effects
on
neurological
development,
a
special
study
designed
to
assess
thyroid
function
in
adult
animals
and
their
offspring
will
be
required.

II.
EXPOSURE
ASSESSMENTS
A.
Dietary
Food
Exposure
Considerations
(Memorandum:
Jose
Morales
to
Carol
Christensen
on
November
27,
2001)

Pronamide
[3,5­
dichloro­
N­(
1,1­
dimethyl­
2­
propynyl)
benzamide]
is
a
selective,
systemic,
pre­
and
post­
emergence
herbicide
registered
for
the
control
of
grasses
and
broadleaf
weeds
in
several
food
and
feed
crops
as
well
as
woody
ornamentals,
Christmas
trees,
nursery
stocks,
lawns,
turfs,
and
fallow
land.
The
application
rates
range
from
0.2
lbs
ai/
A
to
4.0
lbs
ai/
A
and
can
be
applied
1
to
2
times
per
season.
There
are
no
Codex
MRLs
established
or
proposed
for
residues
of
pronamide
in
or
on
foods.
Tolerances
range
from
0.05­
10
ppm.

Pronamide
is
a
systemic
herbicide.
The
qualitative
nature
of
the
residue
in
plants
and
3
animals
is
adequately
understood.
The
terminal
residues
of
concern
are
pronamide
and
its
metabolites
containing
the
3,5­
dichlorobenzoyl
moiety.
Monitoring
data
are
available
from
the
Pesticide
Data
Program
(PDP)
for
the
years
1998
and
1999.
There
were
only
2
instances
of
detectable
residues.
Percent
of
crop
treated
data
are
also
available.

The
HED
Dietary
Exposure
Evaluation
Model
(DEEM)
will
be
used
to
assess
the
risk
from
dietary
exposure
to
pronamide
residues
in
food.
The
DEEM
analysis
will
be
refined
(Tier
II)
using
anticipated
residues
and
percent
of
crop
treated
data.

The
Committee
recognizes
that
further
refinement
to
the
dietary
food
exposure
analyses
may
be
required
as
the
risk
assessment
is
developed.
Therefore,
provided
the
final
dietary
food
exposure
assessment
includes
the
metabolites
of
toxicological
concern
does
not
underestimate
the
potential
risk
for
infants
and
children,
the
safety
factor
recommendations
of
this
Committee
stand.

B.
Dietary
Drinking
Water
Exposure
Considerations
(Correspondence:
Lucy
Shanaman
to
Carol
Christensen
on
November
27,
2001)

The
environmental
fate
data
base
for
the
parent
compound
(pronamide,
also
known
as
propyzamide)
is
complete.
Pronamide
is
relatively
mobile
and
persistent
in
the
environment,
and
therefore
could
possibly
move
to
surface
and
groundwater.
Only
the
parent
compound
pronamide
is
assessed
in
the
drinking
water
exposure
analysis.
Laboratory
studies
indicate
that
leaching
appears
to
be
the
major
route
of
dissipation
for
pronamide.

The
FIRST
and
SCI­
GROW
models
will
be
used
to
estimate
environmental
concentrations
(EEC's)
of
pronamide
in
surface
water
and
groundwater.
These
models
are
considered
Tier
I.
The
ornamental
application
scenario
is
used
to
assess
water
exposure
because
application
rate
and
frequency
associated
with
this
use
is
expected
to
result
in
the
highest
modeled
EECs.
Monitoring
data
were
not
used
in
this
assessment
directly.
However,
available
data
do
indicate
that
the
values
estimated
through
modeling
are
conservative.

The
FQPA
Safety
Factor
Committee
recognizes
that
further
refinement
to
the
dietary
drinking
water
exposure
analyses
may
be
required
as
the
risk
assessment
is
developed.
Therefore,
provided
the
final
dietary
water
exposure
assessment
does
not
underestimate
the
potential
risk
for
infants
and
children,
the
safety
factor
recommendations
of
this
Committee
stand.
4
C.
Residential
Exposure
Considerations
(Correspondence:
Barry
O'Keefe
to
Carol
Christensen
on
November
27,
2001)

Use
of
pronamide
in
the
residential
environment
is
by
certified
applicators
only.
Postapplication
dermal
and
incidental
oral
exposures
to
children
and
infants
are
possible
from
exposure
to
lawns
and
turf
treated
with
pronamide.
Typical
application
rates
are
0.5
to
1.0
lbs
ai/
acre.
Applications
to
turf
are
only
made
in
the
late
Fall
or
late
Winter.
Therefore,
for
residential
turf,
it
is
reasonable
to
assume
that
typically
one
or
two
applications
are
made
per
year.
If
two
applications
were
made,
one
would
probably
be
made
in
late
Fall,
followed
by
another
application
in
late
Winter.

Both
a
registrant
submitted
turf
transferable
residue
(TTR)
study
and
the
EPA's
original
and
revised
Draft
SOPs
for
Residential
Exposure
Assessment
were
used
to
assess
postapplication
dermal
exposure
to
adults
and
children
as
well
as
incidental
oral
exposure
of
toddlers.
A
100%
dermal
absorption
factor
was
assumed.
Incident
data
are
available,
and
report
only
a
few
exposures.
5
II
SAFETY
FACTOR
RECOMMENDATION
AND
RATIONALE
A.
Recommendation
of
the
Factor
The
Committee
recommended
that
the
FQPA
safety
factor
be
reduced
to
3x.

B.
Rationale
for
Reducing
the
FQPA
Safety
Factor
The
FQPA
Committee
determined
that
the
safety
factor
is
necessary
when
assessing
the
risk
posed
by
pronamide
because:

1.
There
is
evidence
of
endocrine
effects
(thyroid,
testes,
ovaries,
adrenal
glands,
pituitary
gland,
thymus)
identified
in
the
majority
of
studies
conducted
across
species.
A
special
study
designed
to
assess
thyroid
function
in
adult
animals
and
their
offspring
will
be
required.

However,
the
Committee
concluded
that
the
safety
factor
could
be
reduced
for
pronamide
because:

1.
The
toxicological
database
is
adequate
for
FQPA
assessment;
and,
2.
There
is
no
indication
of
quantitative
or
qualitative
increased
susceptibility
of
rabbits
to
in
utero
exposure
or
to
rats
following
pre/
postnatal
exposure.
Also,
in
the
available,
unacceptable
rat
study,
no
increased
susceptibility
was
seen
even
though
the
animals
could
have
tolerated
higher
doses.
3.
A
developmental
neurotoxicity
study
is
not
required;
and,
4.
The
dietary
(food
and
drinking
water)
and
residential
exposure
assessments
will
not
underestimate
the
potential
exposures
for
infants
and
children.

C.
Application
of
the
Safety
Factor
­
Population
Subgroups/
Risk
Assessment
Scenarios:

All
population
subgroups:
The
3x
FQPA
Safety
factor
will
be
applied
when
assessing
chronic
dietary
and
short­
term
residential
exposure
scenarios
because
of
evidence
of
endocrine
effects.
