1
Formetanate
HCl
Overview
of
Risk
Assessment
March
11,
2004
Introduction
This
document
summarizes
EPA's
human
health,
environmental
fate,
and
ecological
risk
findings
for
the
pesticide
formetanate
hydrochloride
(
HCl).
These
findings
are
presented
fully
in
the
human
health
risk
assessment
document
"
HED
Revised
Risk
Assessment
for
Formetanate
Hydrochloride"
dated
June
4,
2003;
and
the
"
EFED
Science
Chapter
for
the
Formetanate
Hydrochloride
Reregistration
Eligibility
Document",
dated
October
22,
2003.

Formetanate
HCl
is
a
carbamate
insecticide,
and
it
has
been
determined
that
N­
methyl
carbamates
share
a
common
mechanism
of
toxicity:
the
inhibition
of
cholinesterase.
As
required
by
the
Food
Quality
Protection
Act
(
FQPA),
EPA
will
consider
the
cumulative
risks
from
food,
water
and
non­
occupational
exposure
resulting
from
all
revelant
uses
of
the
group
of
N­
methyl
carbamates.
The
risk
estimates
summarized
in
this
document,
however,
are
for
formetanate
HCl
alone.

In
October
1999,
a
Memorandum
of
Agreement
(
MOA)
between
the
registrant
and
the
Agency
was
signed
because
EPA
was
concerned
that
formetanate
residues
from
the
current
use
pattern
presented
acute
dietary
risks.
In
addition,
EPA
was
also
concerned
with
worker
and
ecological
risks
(
These
findings
are
presented
fully
in
the
human
health
risk
assessment
document
"
HED
Preliminary
Risk
Assessment
for
Formetanate
Hydrochloride"
dated
April
6,
1999;
and
EFED
Science
Chapter
for
the
Formetanate
Hydrochloride
Reregistration
Eligibility
Document
dated
September
29,
1997).

For
acute
dietary
risks,
the
Agency
concluded
if
changes
to
application
rates
and/
or
timing
to
citrus,
stone,
and
pome
fruits
were
to
result
in
non­
detectable
residues,
risk
estimates
would
probably
be
below
EPA's
level
of
concern.
The
MOA
stipulated
labeling
amendments
aimed
at
lowering
application
rates,
increasing
pre­
harvest
intervals
and
limiting
uses
to
certain
crops
in
an
effort
to
reduce
exposures
associated
with
formetanate
uses.
In
addition,
the
registrant
would
supply
the
Agency
with
field
trial
data
for
citrus,
nectarines,
peaches,
and
apples.
Further,
they
would
submit
acute,
subchronic,
and
developmental
neurotoxicity
studies
for
the
hazard
assessment.

Finally,
the
MOA
stipulated
that
if,
on
the
basis
of
new
data,
EPA
determines
that
residues
exceed
100%
of
the
acute
Population
Adjusted
Dose
(
aPAD),
the
Registrant
may
either
withdraw
the
registrations
or
amend
them
to
demonstrate
that
the
formetanate
HCl
residues
on
food
do
not
exceed
100%
of
the
aPAD.
2
The
risk
assessments
summarized
here
are
based
on
the
new
application
rates/
timing
and
toxicity
information
submitted
in
response
to
the
MOA
and
consider
only
those
uses
allowed
under
the
MOA.
The
purpose
of
this
overview
is
to
assist
the
reader
in
understanding
the
conclusions
reached
in
the
risk
assessments
by
identifying
the
key
features
and
findings
of
each.

Use
Profile
$
Insecticide:
Formetanate
HCl
is
a
carbamate
miticide/
insecticide
used
on
alfalfa
(
grown
for
seed),
apples,
pears,
nectarines,
peaches,
and
assorted
citrus
fruits.
There
are
no
residential
uses
for
formetanate
products.

$
Target
Pests:
Registered
products
containing
formetanate
HCl
are
intended
for
application
on
fruit
and
alfalfa
to
control
lygus
bugs,
mites,
stink
bugs,
and
thrips.

$
Formulations:
Formetanate
HCl
is
formulated
as
a
manufacturing
product
(
92
percent
active
ingredient),
and
as
a
wettable
powder
in
water
soluble
packaging
(
92
percent
active
ingredient).

$
Method
of
Application:
Formetanate
HCl
can
be
applied
with
aerial
or
ground
equipment,
such
as
groundboom
sprayers
and
airblast
sprayers.
Formetanate
HCl
is
labeled
for
use
on
tree
fruits
at
1.15
lb
ai/
A
and
for
alfalfa
at
a
maximum
of
0.92
lb
ai/
A.

$
Use
Summary:
Based
on
Agency
data,
the
average
total
annual
domestic
usage
of
formetanate
was
approximately
60,000
pounds
a.
i.
on
about
65,000
acres.
The
predominant
usage
is
in
California.
The
highest
usage,
by
crop,
is
on
nectarines
where
it
is
50­
70%
crop
treated.

$
Technical
Registrant:
Gowan
Company.

Human
Health
Risk
Assessment
Results
of
the
MOA
Agreement
Between
2000­
2002,
the
registrant
submitted
field
trial
data
using
the
new
application
rate/
timing
for
formetanate.
New
labels
were
approved
on
January
27,
2000
(
they
were
submitted
to
EPA
on
November
23,
1999)
to
reflect
the
amendments
that
were
set
forth
by
the
MOA.
Acute
and
subchronic
neurotoxicity
data
were
submitted
for
Agency
review.
EPA
has
since
concluded
that
a
developmental
neurotoxicity
study
in
rats
is
not
required
but
that
comparative
cholinesterase
assay
studies
are
needed.

USDA's
Pesticide
Data
Program
(
PDP),
upon
Agency
request,
collected
and
analyzed
3
oranges,
apples
and
nectarines
in
2000
and
2001
in
order
to
determine
formetanate
residues
resulting
from
the
new
lower
application
rates
mandated
by
the
MOA.
2001
PDP
data
were
used
in
the
dietary
assessment
because
it
is
unlikely
that
label
changes
were
in
effect
for
the
full
2000
growing
season.
Limited
field
trial
data
were
available
at
the
new
application
rates
for
nectarine,
peach,
apple,
pear,
orange,
grapefruit,
and
lemon
and
these
data
showed
residues
from
applications
made
in
accordance
to
the
MOA.

Hazard
Uncertainties
The
toxicology
assessment
for
formetanate
has
changed
from
the
1999
Human
Health
Risk
Assessment
based
on
the
submitted
data.
In
particular,
there
were
significant
changes
in
the
endpoint
and
uncertainty
factors
(
See
Table
1
below).
The
previous
endpoint
was
1
mg/
kg/
day
based
on
cholinergic
effects
(
salivation
and
tremors)
from
a
developmental
toxicity
study
in
rats.
The
current
NOAEL,
based
on
the
new
acute
neurotoxicity
study,
is
0.1
mg/
kg/
day
where
the
endpoint
is
cholinesterase
inhibition.

The
Uncertainty
Factors
in
1999
were
900x.
There
was
a
10x
for
interspecies,
10x
for
intraspecies,
3x
for
lack
of
a
true
NOAEL
(
since
cholinesterase
inhibition
was
not
measured)
and
a
3x
for
the
FQPA
safety
factor
because
data
gaps
existed
for
acute
and
subchronic
neurotoxicity
studies
in
rats.
The
registrant
provided
acute
and
subchronic
neurotoxicity
studies,
so
the
3x
FQPA
safety
factor
was
removed.
In
addition,
since
the
acute
neurotoxicity
study
measured
cholinesterase
inhibition,
the
3x
for
lack
of
true
NOAEL
was
removed.

However,
formetanate
has
been
demonstrated
to
be
an
inhibitor
of
cholinesterase
and
at
higher
doses
to
demonstrate
signs
of
toxicity
related
to
cholinesterase
inhibition.
Thus,
based
on
structure
activity
relationships
and
the
demonstration
of
toxicity
related
to
cholinesterase
inhibition
there
is
a
need
for
additional
testing
to
evaluate
the
susceptibility
of
newborns
to
cholinesterase
inhibition.
Therefore,
a
special
study
that
compares
cholinesterase
inhibition
in
adult
rats
with
neonatal
rats
is
required
to
determine
potential
sensitivity
of
the
young
compared
to
the
adults.
Until
this
data
is
submitted,
the
Agency
concluded
that
a
10x
Database
Uncertainty
Factor
is
warranted.
Available
data
provide
no
basis
to
support
reduction
or
removal
of
the
Uncertainty
Factor.

Exposure
Uncertainties
2001
PDP
data
reflects
current
labels.
However,
they
may
also
reflect
some
carryover
use
(
i.
e.,
applications
from
product
prior
to
label
changes).
EPA
is
analyzing
2001
and
2002
California
use
data
(
for
nectarines
only)
in
an
attempt
to
resolve
this
uncertainty.
4
Acute
Dietary
(
Food)
Risk
Acute
dietary
risk
is
calculated
considering
the
toxicity
of
a
chemical,
what
is
eaten
by
individuals
in
one
day
and
residue
values
for
various
foods.
A
risk
estimate
that
is
less
than
100%
of
the
acute
Population
Adjusted
Dose
(
aPAD)
(
the
dose
at
which
an
individual
could
be
exposed
on
any
given
day
and
no
adverse
health
effects
would
be
expected)
does
not
exceed
the
Agency's
risk
concern.

Table
1.
Formetanate
HCl
:
Summary
of
the
2003
Toxicology
Endpoint
Selection
Acute
Dietary
Endpoint
Exposure
Scenario
Dose
Endpoint
Study
Acute
Dietary
(
2003)
NOAEL=
0.1
mg/
kg
Whole
Blood
and
Brain
Cholinesterase
Inhibition
Acute
Neurotoxicity
Study
UF
=
1000x
Acute
PAD
=
0.0001
mg/
kg/
day
$
The
acute
dietary
risk
endpoint
is
based
the
inhibition
of
whole
blood
and
brain
cholinesterase
activity
in
rats
at
a
NOAEL
of
0.1
mg/
kg/
day.
This
NOAEL
is
a
10
fold
decrease
from
the
endpoint
that
was
established
in
1999
(
1
mg/
kg/
day).

$
The
Uncertainty
Factor
is
1000.
10x
interspecies
extrapolation,
10x
for
intra­
species
variability,
and
10x
for
an
additional
database
uncertainty
factor
to
account
for
the
lack
of
a
special
comparative
cholinesterase
study
in
adults
versus
young.

$
The
acute
RfD
is
calculated
to
be
0.0001
mg/
kg/
day.
Because
the
FQPA
safety
factor
was
reduced
to
1x,
the
acute
and
chronic
RfDs
are
equal
to
the
acute
and
chronic
PADs,
respectively.
The
acute
Population
Adjusted
Dose
(
aPAD)
is
0.0001
mg/
kg/
day.

$
The
Dietary
Evaluation
Exposure
Model
software
with
the
Food
Commodity
Intake
Database
(
DEEM­
FCIDTM,
Version
1.3)
was
used
to
estimate
acute
dietary
exposure
in
a
probabilistic
mode.

$
The
acute
dietary
risk
analysis
evaluates
individual
food
consumption
as
reported
by
respondents
in
the
USDA
1994­
1996
and
1998
Continuing
Survey
of
Food
Intake
by
Individuals
(
CSFII)
and
accumulates
exposure
to
the
chemical
for
each
commodity.

$
This
analysis
is
refined
in
that
it
uses
2001
monitoring
data
from
USDA's
Pesticide
Data
Program
to
calculate
anticipated
residues
for
use
in
acute
dietary
analysis.
Data
on
the
percentage
of
crop­
treated
were
incorporated
for
all
commodities
included
in
the
dietary
assessment.

$
The
acute
dietary
risk
(
food)
of
formetanate
HCl
is
above
the
Agency's
level
of
concern
5
(
i.
e.,
greater
than
100%
of
the
aPAD
is
utilized)
for
the
general
U.
S.
population
and
all
population
subgroups,
including
infants
and
children
at
the
99.9th
percentile
of
exposure.
The
most
highly
exposed
subgroup
was
infants
at
3300%
of
the
aPAD.

Table
2.
Formetanate
HCl:
Acute
Dietary
Risk
%
aPAD
at
99.9th
Percentile
Population
Subgroup
%
aPAD
General
U.
S.
Population
640
All
Infants
(<
1
year
old)
3300
Children
1­
2
years
old
2200
Children
3­
5
years
old
1600
Children
6­
12
years
old
870
Youth
13­
19
years
old
340
Adults
20­
49
years
old
460
Females
13­
49
years
old
520
Adults
50+
years
old
530
Chronic
Dietary
(
Food)
Risk
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
PAD
(
the
dose
at
which
an
individual
could
be
exposed
over
the
course
of
a
lifetime
and
no
adverse
health
effects
would
be
expected)
does
not
exceed
the
Agency's
risk
concern.
The
cPAD
is
the
chronic
reference
dose
(
cRfD)
adjusted
for
the
FQPA
Safety
Factor.
As
noted
above,
since
the
FQPA
Safety
Factor
equals
1,
they
are
the
same.

Chronic
risk
estimates
from
exposures
in
food
to
formetanate
HCl
are
below
the
Agency's
level
of
concern
for
the
general
U.
S.
population
and
all
population
subgroups.
The
most
highly
exposed
population
subgroup
was
infants
<
1
year
old
at
10%
of
the
cPAD
(
See
Table
3).

$
Since
the
clinical
signs
following
acute
and
chronic
exposure
to
formetanate
in
rats
and
dogs
are
consistent
with
cholinesterase
inhibition,
the
same
endpoint
was
used.
The
chronic
dietary
risk
endpoint
is
based
the
inhibition
of
whole
blood
and
brain
cholinesterase
activity
in
rats
at
a
NOAEL
of
0.1
mg/
kg/
day.
These
effects
were
observed
at
1
mg/
kg/
day.

$
As
stated
above
for
the
acute
dietary
risk,
the
Uncertainty
Factor
is
1000.

$
The
chronic
RfD
is
calculated
to
be
0.0001
mg/
kg/
day.
6
$
The
Dietary
Evaluation
Exposure
Model
software
with
the
Food
Commodity
Intake
Database
(
DEEM­
FCIDTM,
Version
1.3)
was
used
to
estimate
chronic
dietary
exposure
which
incorporated
consumption
data
from
CSFII
1994­
1996
and
1998.
Anticipated
residues
from
2001
USDA
PDP
monitoring
data,
estimated
percent
crop
treated
information
and
processing
factors
were
used.

Drinking
Water
Dietary
Risk
Drinking
water
exposure
to
pesticides
can
occur
through
groundwater
and
surface
water
contamination.
EPA
considers
both
acute
(
one
day)
and
chronic
(
multiple
year)
drinking
water
risks,
and
uses
either
modeling
or
monitoring
data,
if
available,
to
estimate
those
risks.
Modeling
is
carried
out
in
tiers
of
further
refinement,
but
is
designed
to
provide
a
high­
end
estimate
of
exposure.
To
determine
the
maximum
allowable
contribution
from
water
in
the
diet,
EPA
first
calculates
the
overall
allowable
risk
and
subtracts
the
amount
contributed
by
food
to
determine
a
"
drinking
water
level
of
comparison"
(
DWLOC).
This
is
then
compared
to
estimated
concentrations
in
water
to
ascertain
whether
modeled
or
monitoring
levels
in
water
exceed
this
level
of
risk.
The
acute
DWLOC
estimate
could
not
be
calculated
for
formetanate
HCl
since
more
than
the
allowable
portion
of
risk
was
contributed
by
residues
in
food.

$
Formetanate
HCl
is
moderately
mobile
but
degrades
quickly
in
aquatic
environments.

$
Drinking
water
concentrations
for
ground
water
were
estimated
using
model
estimates
from
the
SCI­
GROW
2.3
model.
Drinking
water
concentrations
for
surface
water
were
estimated
using
the
Tier
2
PRZM/
EXAMS
model.
No
ground
water
or
surface
water
monitoring
data
were
available.

Acute
Exposures
$
Because
acute
exposure
to
residues
of
formetanate
HCl
from
food
alone
exceeds
EPA's
level
of
concern,
additional
exposure
to
formetanate
HCl
in
drinking
water
would
cause
risk
estimates
to
further
exceed
levels
of
concern.
Effectively,
until
the
acute
dietary
(
food)
exposure
to
formetanate
HCl
is
reduced,
DWLOCs
are
assumed
to
be
zero.

$
Potential
exposure
to
formetanate
HCl
from
drinking
water
derived
from
ground
water
sources
results
in
an
acute
estimated
environmental
concentration
(
EEC)
of
0.29
ppb.

$
Potential
exposure
to
formetanate
HCl
from
drinking
water
derived
from
surface
water
results
in
an
acute
EEC
of
7.68
ppb.

Chronic
Exposures
7
Potential
exposure
to
formetanate
from
drinking
water
derived
from
surface
water
results
in
a
chronic
EEC
of
0.08
ppb.
For
groundwater
modeling,
degradation
is
assumed
to
be
negligible.
Therefore,
the
chronic
groundwater
EEC
is
0.29
ppb.
All
EECs
are
less
than
the
chronic
DWLOCs
for
each
population.
Therefore,
the
Agency
is
not
concerned
with
potential
chronic
exposure
to
formetanate
through
surface
and
ground
water.

Table
3.
Formetanate:
Chronic
Dietary
Risk
%
cPAD
at
99.9th
Percentile
and
Drinking
Water
DWLOC
and
EEC
Comparisons
Population
Subgroup
%
aPAD
DWLOC
EECs
(
ppb)

Chronic
Ground
Water
Surface
Water
General
U.
S.
Population
3
3.4
0.29
0.08
All
Infants
(<
1
year
old)
10
0.90
Children
1­
2
years
old
9
0.91
Children
3­
5
years
old
8
0.92
Children
6­
12
years
old
4
0.96
Youth
13­
19
years
old
1
3.4
Adults
20­
49
years
old
2
3.4
Females
13­
49
years
old
2
2.9
Adults
50+
years
old
2
3.4
Cancer
Risk
Formetanate
HCl
has
been
classified
a
Group
"
E"
carcinogen
(
no
evidence
of
carcinogenicity).
Therefore,
risks
from
formetanate
are
below
the
EPA's
level
of
concern
for
cancer.

Residential
Risk
Currently,
there
are
no
registered
residential
uses
for
formetanate
HCl.

Aggregate
Risk
Acute
exposure
to
residues
of
formetanate
HCl
from
food
alone
exceeds
the
Agency's
level
of
concern.
Additional
exposure
to
formetanate
HCl
in
drinking
water
would
cause
risk
estimates
to
further
exceed
levels
of
concern.
Until
the
acute
dietary
(
food)
exposure
to
formetanate
is
reduced,
DWLOCs
are
assumed
to
be
zero.
Therefore,
acute
aggregate
risks
exceed
EPA's
level
of
concern.

Chronic
aggregate
risk
estimates
are
below
the
Agency's
level
of
concern
for
the
general
8
U.
S.
population
and
all
population
subgroups.

Occupational
Risk
Workers
can
be
exposed
to
a
pesticide
through
mixing,
loading,
applying,
flagging,
and
otherwise
handling
a
pesticide
as
well
as
reentering
previously
treated
sites.
Worker
risk
is
expressed
as
a
Margin
of
Exposure
(
MOE)
which
determines
how
close
the
occupational
exposure
comes
to
an
No
Observed
Adverse
Effect
Level
(
NOAEL),
which
is
the
highest
dose
given
in
studies
at
which
no
significant
toxic
effects
were
observed.
For
formetanate,
MOEs
less
than
100
exceed
the
Agency's
level
of
concern
for
risk
for
short
and
intermediate
term
occupational
dermal
and
inhalation
exposure
(
1­
30
days
and
30
days
to
several
months,
respectively).

Restricted
entry
intervals
(
REIs)
are
calculated
to
determine
the
minimum
length
of
time
required
following
an
application
before
it
is
considered
safe
for
workers
to
reenter
a
treated
area.
REIs
are
developed
for
different
crops
and
different
worker
activities
(
i.
e.,
scouting,
harvesting,
etc.)
using
an
MOE­
based
approach.
For
this
assessment,
REIs
are
calculated
in
days.

Short­
Term
and
Intermediate­
Term
Handler
Risks
$
Formetanate
use
patterns
show
that
both
short­
term
and
intermediate
term
exposure
to
handlers
is
possible.

$
The
short­
term
and
intermediate
endpoints
are
the
same.
The
NOAEL
is
10
mg/
kg/
day
and
is
based
on
a
21­
day
dermal
study
in
rats.
No
dermal
absorption
adjustment
is
required
since
the
endpoint
is
based
on
a
dermal
study.

$
The
short­
term
and
intermediate­
term
inhalation
endpoints
are
also
the
same.
The
NOAEL
is
0.1
mg/
kg/
day
and
is
based
on
the
acute
neurotoxicity
study
in
rats
discussed
above.
An
oral
endpoint
was
chosen
because
of
a
lack
of
inhalation
toxicity
studies.
An
absorption
factor
of
100%
is
assumed
for
exposure
via
the
inhalation
route.

$
No
chemical­
specific
handler
data
were
submitted,
so
short­
term
and
intermediate­
term
dermal
and
inhalation
exposures
for
handlers
were
developed
using
the
Pesticide
Handler
Exposure
Database
(
PHED)
Version
1.1.

°
Most
scenarios
had
MOEs
above
100
at
maximum
PPE
(
coveralls,
hood,
gloves,
and
respirator)
or
maximum
PPE
using
engineering
controls.
The
exceptions
were
at
maximum
PPE,
mixing
and
loading
for
alfalfa
by
aerial
application
(
MOE
=
57)
and
airblast
applicators
for
orchards
(
MOE=
73).
With
engineering
controls,
EPA
has
concerns
for
aerial
applicators
for
alfalfa
(
MOE
=
54).
The
following
tables
summarize
the
risks
to
handlers
by
crop
type:
Table
4:
Mixer­
Loader,
Applicator,
Flagger
Risk
Estimates
using
WP
in
Water
Soluble
Packets
(
WSP
plus
Double
Layer
Protection,
Gloves,
Dust/
Mist
Respirator
1Refer
to
Table
5.

2
Engineering
control
exposures
represent
long
pants
and
long
sleeved
shirts.
For
mixers
and
loaders,
chemical­
resistant
gloves
are
also
included.

9
Exposure
Scenario
Crop
Application
Rate
lb
ai/
A
Dermal
MOE
Inhalation
MOE
Total
MOE
Mixer
Loader
(
Wettable
Powders)

Aerial
Pome,
Stone,
Citrus
1.15
305
360
170
Aerial
Alfalfa
for
seed
0.92
110
130
57
Airblast
Pome,
Stone,
Citrus
1.15
2700
3200
1500
Groundboom
Alfalfa
0.92
670
709
340
Applicator
(
Sprays)

Aerial
Alfalfa
0.92
Not
Practical1
Not
Practical
Not
Practical
Aerial
Pome,
Stone,
Citrus
1.15
Not
Practical
Not
Practical
Not
Practical
Airblast
Pome,
Stone,
Citrus
1.15
130
170
73
Groundboom
Alfalfa
for
seed
0.92
350
250
150
Flagger
Aerial
Alfalfa
for
seed
0.92
220
310
130
Aerial
Stone,
Pome,
Citrus
1.15
170
250
100
Table
5:
Formetanate
HCl.
Mixer/
Loader,
Applicator,
&
Flagger
Risk
Estimates:
Using
Engineering
Controls:
WP
in
Water
Soluble
Bags
(
WSB);
Closed
Cockpit,
Closed
Cab
Tractors2
Exposure
Scenario
Crop
Application
Rate
(
lb
ai/
A)
Dermal
MOE
Inhalation
MOE
Total
MOE
Mixer
Loader
(
Wettable
Powder)

Aerial
Pome,
Stone,
Citrus
1.15
180
72
51
Aerial
Alfalfa
for
seed
0.92
65
26
19
Airblast
Pome,
Stone,
Citrus
1.15
1600
630
450
Exposure
Scenario
Crop
Application
Rate
(
lb
ai/
A)
Dermal
MOE
Inhalation
MOE
Total
MOE
10
Groundboom
Alfalfa
0.92
390
160
110
Applicator
(
Sprays)

Aerial
Alfalfa
0.92
130
93
54
Aerial
Pome,
Stone,
Citrus
1.15
350
260
150
Airblast
Pome,
Stone,
Citrus
1.15
800
340
240
Groundboom
Alfalfa
for
seed
0.92
760
890
410
Flagger
Aerial
Alfalfa
for
seed
0.92
9900
3100
2400
Aerial
Stone,
Pome,
Citrus
1.15
7900
2500
1900
Post­
Application
Risk
Estimates
There
is
potential
exposure
to
persons
entering
previously
treated
sites
(
e.
g.
scouts
and
harvesters).
The
use
of
standard
transfer
coefficients
was
used
to
represent
transfer
during
worker
activities
for
each
of
the
crops.
Dislodgeable
foliar
residue
(
DFR)
values
are
based
on
a
formetanate
HCl
study
on
citrus.
The
citrus
DFR
values
were
then
used
as
surrogate
data
for
all
other
crops.

$
Formetanate
HCl
use
patterns
show
that
both
short­
term
(
1­
30
days)
and
intermediateterm
(
1
month
to
6
months)
exposure
is
possible
for
post­
application
exposures.
Therefore,
risk
estimates
were
calculated
for
both
short­
term
and
intermediate­
term
exposures.

$
The
Agency
has
adopted
a
method
of
clustering
crops,
crop
growth
stages,
and
postapplication
activities
into
groups
that
are
expected
to
result
in
comparable
exposure.
Empirically
derived
transfer
coefficients
have
then
been
applied
to
activities
occurring
in
the
defined
crop
groups.
The
transfer
coefficient
defines
the
rate
of
transfer
from
foliar
residue
to
skin
that
occurs
during
a
particular
activity.

$
Dislodgeable
Foliar
Residue
(
DFR)
data
were
submitted
for
citrus.
This
data
was
translated
for
use
on
pome
and
stone
fruit.
The
assessment
was
adjusted
to
reflect
the
current
maximum
use
rate.
In
addition,
this
assessment
is
assumed
to
be
representative
for
all
registered
tree
crops.
11
$
No
residue
data
were
submitted
for
alfalfa.
Data
from
the
citrus
study
was
translated
for
alfalfa.
The
Agency
acknowledges
that
the
citrus
residue
data
are
not
readily
comparable
to
alfalfa
residues.
However,
the
calculated
exposure
using
the
surrogate
data
is
being
used
as
a
screening
level
assessment
and
is
considered
a
conservative
estimate
for
alfalfa.

$
For
worker
re­
entry
risk,
the
calculated
REI
represents
the
day
on
which
the
MOE
is
greater
than
or
equal
to
100.
MOEs
were
greater
than
or
equal
to
a
100
by
day
12
for
evergreen
fruit
trees,
day
8
for
deciduous
fruit
trees,
and
day
9
for
alfalfa.

Table
6.
Formetanate
HCl.
Summary
of
Postapplication
Risks
Crops
Re­
entry
Day
with
Acceptable
MOEs
>
100
Alfalfa
9
Fruit
Trees,
Deciduous
8
Fruit
Trees,
Evergreen
12
Ecological
Risk
Assessment
To
estimate
potential
ecological
risks,
EPA
integrates
the
results
of
exposure
and
ecotoxicity
using
the
quotient
method.
Risk
quotients
(
RQs)
are
calculated
by
dividing
estimated
environmental
concentrations
(
EECs)
of
the
pesticide
by
acute
and
chronic
toxicity
values.
EECs
are
based
on
the
maximum
application
rates
for
that
pesticide.

Risk
quotients
are
then
compared
to
the
Agency's
level
of
concern
(
LOCs).
These
LOCs
(
Table
7)
are
used
to
analyze
potential
risk
to
non­
target
organisms
and
to
determine
the
need
for
regulatory
action.
Risk
characterization
provides
further
information
on
the
likelihood
of
adverse
effects
occurring
by
considering
the
fate
of
the
chemical
in
the
environment,
communities
and
species
potentially
at
risk,
their
spatial
and
temporal
distributions,
and
the
nature
of
the
effects
observed
in
studies.
If
the
RQ
is
higher
than
the
LOC,
the
Agency
may
have
a
concern.

Table
7.
Formetanate
Hcl:
Risk
Presumptions
for
Terrestrial
and
Aquatic
Animals
Risk
Presumption
LOC
terrestrial
animals
LOC
aquatic
animals
12
Acute
High
Risk
there
is
potential
for
acute
risk
based
on
LD50s
(
i.
e.,
endpoint
is
death
to
50%
of
tested
population)
0.5
0.5
Acute
Restricted
Use
­
there
is
potential
for
acute
risk,
but
may
be
mitigated
through
restricted
use
classification,
0.2
0.1
Acute
Endangered
Species
­
endangered
species
may
be
adversely
affected
0.1
0.05
Chronic
Risk
­
there
is
potential
for
chronic
risk;
effects
are
varied,
but
often
include
reproduction
or
survival
effects.
1
1
Environmental
Fate
Information
$
Formetanate
HCl
is
not
a
persistent
pesticide
under
normal
use
conditions.
The
primary
routes
of
dissipation
appear
to
be
hydrolysis
under
neutral
and
alkaline
conditions
as
well
as
microbial
degradation.
Formetanate
HCl
hydrolyzes
with
a
half­
life
of
less
than
a
1
day.
Photolysis
may
be
an
important
route
of
degradation
in
neutral
and
alkaline
waters
and
on
soil
surfaces
with
half­
lives
ranging
from
less
than
1
to
3
days.
Formetanate
is
readily
biodegradable
with
a
soil
metabolism
half­
life
of
less
than
one
week.

Nontarget
Terrestrial
Animal
Risk
$
Avian
acute
risks
from
a
single
application
were
generally
low.
However,
endangered
species
risks
were
above
the
Agency's
level
of
concern
with
a
maximum
RQ
of
0.20.

$
Avian
chronic
risks
from
a
single
application
were
above
EPA's
level
of
concern
for
most
uses.
Body
weight
and
reproduction
effects
were
seen
at
480
ppm
treatment
levels.
Chronic
RQs
ranged
from
0.26
to
5.21.

$
For
small
mammals
(
15g),
acute
risks
were
above
the
Agency's
level
of
concern
with
RQ
estimates
up
to
1.11.
For
medium
size
(
35g)
animals,
acute
risks
were
below
the
level
of
concern.
However
acute
restricted
use
and
endangered
species
risks
were
above
the
EPA's
level
of
concern
with
RQ
estimates
ranging
up
to
0.24.

$
Mammalian
chronic
risks
from
a
single
application
were
above
EPA's
level
of
concern
for
most
uses.
Chronic
RQs
ranged
from
1.38
to
27.60.
These
results
were
based
on
a
chronic
dog
study
with
a
NOAEL
of
10
ppm
based
on
brain
cholinesterase
inhibition.

$
Formetanate
HCl
is
practically
non­
toxic
to
honeybees.

Nontarget
Aquatic
Animal
Risk
$
Acute
and
chronic
risks
for
freshwater
fish
at
the
single
application
rate
are
below
the
Agency's
level
of
concern
for
all
uses.

$
Acute
and
chronic
risks
for
freshwater
invertebrates
were
generally
below
the
level
of
13
concern
at
the
single
application
rate.
RQ
risk
estimates
exceeded
the
level
of
concern
for
use
on
peaches
(
1.12).
The
effect
noted
for
chronic
risk
was
larval
survival.

$
Acute
risks
for
estuarine/
marine
invertebrates
at
the
single
application
rate
were
below
EPA's
level
of
concern.
No
data
were
submitted
to
estimate
chronic
risks.

Summary
of
Pending
Data
Toxicology
The
acute
toxicity
data
base
is
currently
supported
by
older
studies
which
are
invalid.
Replacement
studies
for
the
following
acute
toxicity
studies
are
required:

$
870.1100
Acute
oral
toxicity
$
870.1200
Acute
dermal
toxicity
$
870.1300
Acute
inhalation
toxicity
$
870.2500
Primary
dermal
irritation
$
Non­
Guideline
Special
study
for
comparative
(
dams
vs.
pups)
inhibition
of
cholinesterase.
The
protocol
for
this
non­
guideline
study
should
be
submitted
to
OPP
for
review
prior
to
initiating
the
study.

$
870.3465
28
day
Inhalation
Toxicity
Study.

Chemistry
Residue
Chemistry
Deficiencies
$
860.1300
Nature
of
the
Residue
$
860.1500
Crop
Field
Trials­
Additional
field
trail
data
(
apple,
pear,
peach,
and
citrus)
are
needed
to
reassess
tolerances.
For
nectarines,
details
pertaining
to
the
field
procedures
used
in
the
at­
harvest
study
(
i.
e.,
application
method
and
timing,
equipment,
spray
volumes,
tank
mix
adjuvants)
and
multiple
application
rates
must
be
provided.

Product
Chemistry
°
830.7050
Ultraviolet/
Visible
Absorption
°
830.1550
Product
Identity
and
Disclosure
of
Ingredients
14
°
830.1750
Certified
Limits
°
830.1800
Enforcement
Analytical
Method
°
Gowan
Co.
must
either
certify
that
the
suppliers
of
beginning
materials
and
the
manufacturing
process
for
the
formetanate
hydrochloride
MP
have
not
changed
since
the
last
comprehensive
product
chemistry
review
or
submit
a
complete
updated
product
chemistry
data
package.

Environmental
Fate
$
835.4100
Aerobic
Soil
Metabolism
$
835.4200
Anaerobic
Soil
Metabolism
