Document ID: EPA-HQ-OPP-2005-0176-0003
Agency: epa
Document Type: Supporting & Related Material
Title: 
Posted Date: 2005-12-28T05:00Z

UNITED
STATES
ENVIRONMENTAL
PROTECTION
AGENCY
WASHINGTON,
D.
C.
20460
OFFICE
OF
PREVENTION,
PESTICIDES
AND
TOXIC
SUBSTANCES
June
8,
2005
MEMORANDUM
SUBJECT:
ETU
from
EBDCs:
Health
Effects
Division
(
HED)
Human
Health
Risk
Assessment
of
the
Common
Metabolite/
Degradate
ETU
to
Support
Reregistration.

Chemical
ID
No.
600016.
DP
Barcode
No.
D317416
FROM:
Christine
Olinger,
Risk
Assessor
Felecia
Fort,
Chemist/
Risk
Assessor
Timothy
Dole,
CIH/
Risk
Assessor
Reregistration
Branch
1
Health
Effects
Division,
7509C
THROUGH:
Whang
Phang,
Ph.
D.,
Branch
Senior
Scientist
Reregistration
Branch
1
Health
Effects
Division,
7509C
TO:
Tawanda
Spears,
Chemical
Review
Manager
Christina
Scheltema,
Chemical
Review
Manager
Special
Review
and
Reregistration
Division,
7508C
The
attached
human
health
risk
assessment
is
for
ethylene
thiourea
(
ETU)
which
is
the
common
metabolite/
degradate
of
the
ethylene­
bis­
dithiocarbamate
(
EBDC)
fungicides
mancozeb,
maneb
and
metiram.
This
assessment
summarizes
the
human
health
risks
from
exposure
to
ETU
resulting
from
the
use
of
the
parent
EBDCs
on
agricultural
commodities,
turf,
and
ornamentals.

This
assessment
is
partially
based
on
the
ETU
sections
of
the
Human
Health
Risk
Assessments
for
the
parent
EBDCs.
It
has
been
revised
as
appropriate
in
response
to
comments
during
the
public
comment
period
for
these
fungicides.
TABLE
OF
CONTENTS
1.0
EXECUTIVE
SUMMARY
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1
2.0
PHYSICAL/
CHEMICAL
PROPERTIES
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7
3.0
HAZARD
CHARACTERIZATION
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8
3.1
Hazard
Profile
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8
3.2
FQPA
Considerations
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11
3.3
Dose
Response
Assessment
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13
3.4
Endocrine
Disruption
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16
4.0
EXPOSURE
ASSESSMENT
AND
CHARACTERIZATION
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17
4.1
Summary
of
Registered
Uses
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19
4.2
Dietary
Exposure/
Risk
Pathway
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21
4.3
Water
Exposure/
Risk
Pathway
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22
4.3.1
Environmental
Fate
Properties
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22
4.3.2
Surface
Water
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22
4.3.3
Ground
Water
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23
4.4
Acute,
Chronic,
and
Cancer
Dietary
Risk
Analysis
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24
4.4.1
Usage
Data
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24
4.4.2
Processing
Factors
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25
4.4.3
DEEM­
FCID
 
Program
and
Consumption
Information
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25
4.4.4
Acute
Dietary
Risk
Analysis
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26
4.4.5
Chronic
Dietary
Risk
Analysis
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26
4.4.6
Cancer
Dietary
Risk
Analysis
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27
4.4.7
Dietary
Risk
Characterization
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28
4.5
Residential
Exposure/
Risk
Pathway
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29
4.5.1
Home
Garden
Uses
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30
4.5.2
Post
Application
Turf
Risks
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32
5.0
AGGREGATE
RISK
ASSESSMENTS
AND
RISK
CHARACTERIZATION
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35
5.1
Acute
Risk
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35
5.2
Short­
Term
Risk
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36
5.3
Chronic
Risk
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36
5.4
Cancer
Risk
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37
6.0
CUMULATIVE
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38
7.0
OCCUPATIONAL
EXPOSURE
AND
RISK
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39
8.0
DATA
NEEDS/
LABEL
REQUIREMENTS
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40
9.0
SUPPORTING
DOCUMENTATION
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40
Appendix
1.
Usage
Information
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41
1
1.0
Executive
Summary
Introduction
Ethylene
thiourea
(
ETU)
is
a
degradate
and
metabolite
of
the
ethylenebis
dithiocarbamate
(
EBDC)
fungicides
mancozeb,
maneb
and
metiram.
The
EBDCs
are
used
on
agricultural
crops
such
as
vegetables,
fruits
and
nuts,
on
turf
including
golf
courses
and
sod
farms
and
on
ornamentals
including
cut
flowers.
The
EBDCs
are
broad
spectrum
contact
fungicides
used
to
prevent
a
variety
of
fungal
diseases.

Human
health
risk
assessments
have
been
conducted
for
each
of
the
EBDC
fungicides,
and
include
potential
exposures
to
ETU
from
chemical­
specific
uses.
The
purpose
of
this
assessment
is
to
characterize
cumulative
exposure
and
risk
from
ETU
as
a
result
of
all
EBDC
usage,
to
describe
risks
from
all
three
EBDCs
in
broad
terms,
and
to
identify
significant
sources
of
exposure
and
risk.
There
is
a
significant
source
of
ETU
in
the
environment,
and
potential
exposure
to
occupational
workers,
that
stems
from
its
use
as
an
accelerator
in
the
production
of
polychloroprene
(
neoprene)
and
polyacrylate
rubbers.
These
two
types
of
rubbers
are
generally
used
for
industrial
purposes,
such
as
in
wire
and
cable
production,
in
construction,
adhesives,
seals
and
o­
rings,
and
gaskets.
Exposure
to
ETU
from
these
industrial
sources
has
not
been
considered
in
this
human
health
risk
assessment.
However,
some
of
the
industrial­
source
ETU
may
result
in
contamination
of
ground
or
surface
waters,
and
may
not
easily
be
distinguished
from
agricultural
sources.

Regulatory
Background
In
1977,
the
Agency
initiated
a
Special
Review
and
Continued
Registration
of
Pesticide
Products
containing
ethylene
bisdithiocarbamates
(
EBDCs).
The
need
for
Special
Review
of
the
EBDCs
was
based
on
evidence
suggesting
that
the
EBDCs
and
ethylenethiourea
(
ETU)
posed
potential
risks
to
human
health
and
the
environment.
In
1982,
the
Agency
concluded
this
Special
Review
by
issuing
a
Final
Determination
(
PD
4)
which
required
risk
reduction
measures
to
prevent
unreasonable
adverse
effects
pending
development
and
submission
of
additional
data
needed
for
improved
risk
assessment.

In
1987,
EPA
issued
a
second
Notice
of
Initiation
of
Special
Review
of
the
EBDC
pesticides
because
of
health
concerns
caused
by
ETU.
The
Special
Review's
Preliminary
Determination
(
PD
2/
3)
was
published
on
12/
20/
89
(
54
FR
52158)
and
the
Final
Determination
(
PD
4)
on
3/
2/
92
(
57
FR
7484).
The
Agency
concluded
that
the
dietary
risks
of
EBDCs
exceeded
the
benefits
for
the
following
food/
feed
uses
for
which
one
or
more
of
the
EBDC
pesticides
were
registered:
apricots,
carrots,
celery,
collards,
mustard
greens,
nectarines,
peaches,
rhubarb,
spinach,
succulent
beans,
and
turnips.
Accordingly,
EPA
canceled
EBDC
products
registered
on
the
above­
listed
food/
feed
crops.
In
the
1992
special
review,
and
in
the
current
set
of
risk
assessments,
exposure
to
both
the
parent
EBDCs
and
ETU
have
been
considered,
both
for
dietary
and
occupational
risk
assessments.
In
addition,
the
current
risk
assessments
consider
exposure
to
ETU
from
uses
in
residential
settings.
2
Sources
of
ETU
Crops
treated
with
EBDCs
may
contain
both
EBDC
and
ETU
residues;
in
addition,
cooking
and/
or
processing
may
result
in
conversion
of
EBDC
residues
to
ETU,
or
in
concentration
or
reduction
of
existing
ETU
residues.
Therefore,
both
EBDC
and
ETU
residues
may
be
consumed
in
the
diet.
During
application
of
EBDCs,
workers
may
be
exposed
to
ETU
residues
which
form
during
degradation
of
the
tank
mix
over
a
typical
workday,
and
the
Agency
has
data
to
reflect
these
potential
exposures.
Additional
exposure
to
both
EBDCs
and
ETU
may
occur
during
activities
conducted
in
and
around
growing
crops
following
treatment
with
EBDCs.
Finally
metabolic
conversion
of
absorbed
EBDC
to
ETU
occurs
and
has
been
accounted
for
in
calculating
ETU
doses.

ETU
Hazard
Profile
and
Food
Quality
Protection
Act
(
FQPA)
Decision
The
toxicology
database
for
ETU
is
limited
based
on
guideline
studies,
and
HED
has
relied
on
a
combination
of
guideline
data
and
several
studies
in
the
open
literature
to
assess
hazard
for
ETU.
The
thyroid
is
a
target
organ
for
ETU
as
it
is
for
the
EBDC
fungicides;
thyroid
toxicity
in
subchronic
and
chronic
rat,
mouse,
and
dog
studies
included
decreased
levels
of
T4,
increases
or
decreases
in
T3,
compensatory
increases
in
levels
of
TSH,
increased
thyroid
weight,
and
microscopic
thyroid
changes,
chiefly
hyperplasia.
Overt
liver
toxicity
was
observed
in
one
chronic
dog
study.
Developmental
defects
in
the
rat
developmental
study
included
hydrocephaly
and
related
lesions,
skeletal
system
defects,
and
other
gross
defects.
These
defects
showed
increased
susceptibility
to
fetuses
because
they
occurred
at
a
dose
which
only
caused
decreased
maternal
food
consumption
and
body
weight
gain.

Although
the
data
provided
evidence
for
increased
susceptibility
to
fetuses
following
dosing
with
ETU,
HED
removed
(
reduced
to
1X)
the
Special
FQPA
Safety
Factor
because
the
teratogenic
effects
were
well
characterized
in
numerous
studies
in
the
published
literature,
as
well
as
in
a
guideline
study
submitted
by
the
registrant.
In
addition,
the
dose­
response
relationship
was
well
characterized,
and
doses
selected
for
overall
risk
assessments
addressed
concerns
for
developmental
and
thyroid
toxicity.
However,
due
to
the
lack
of
several
required
guideline
studies,
HED
retained
a
10X
database
uncertainty
factor
for
dietary,
residential
and
aggregate
risk
assessments
for
ETU.

ETU
Doses
and
Endpoints
Selected
for
Risk
Assessment
The
doses
and
endpoints
used
for
ETU
are
listed
below.
For
acute
ETU
exposures,
developmental
effects
were
selected
as
the
most
sensitive
endpoint.
This
same
endpoint
was
also
used
for
short
and
intermediate
term
exposures.
For
chronic
exposures,
the
endpoint
was
based
upon
thyroid
effects
that
were
observed
in
the
chronic
dog
study.
ETU
was
also
classified
as
a
group
B2
carcinogen
based
upon
liver
tumors
observed
in
female
mice
and
a
cancer
potency
factor,
Q
1
*,
of
0.0601
mg/
kg/
day
was
used
for
risk
assessment.
3
Exposure
Route,
Duration
ETU
Dose
in
mg/
kg/
day
(
study/
effects)
Acute
dietary
(
females
13­
49)
NOAEL
of
5
(
Developmental
rat/
developmental
brain
defects)
Acute
dietary
(
gen.
US
pop)
No
applicable
endpoint/
dose
identified
Chronic
dietary
(
gen.
US
pop.)
NOAEL
of
0.18
(
Chronic
dog/
thyroid
toxicity)
Incidental
oral,
any
duration
NOAEL
of
7
(
4­
week
Dog/
thyroid
toxicity)
Dermal,
Short/
Int­
Term
NOAEL
of
5
(
Developmental
rat/
developmental
brain
defects)
Dermal,
Long­
Term
NOAEL
of
0.18
(
Chronic
dog/
thyroid
toxicity)
Inhalation,
Short/
Int­
Term
NOAEL
of
5
(
Developmental
rat/
developmental
brain
defects)
Inhalation,
Long­
Term
NOAEL
of
0.18
(
Chronic
dog/
thyroid
toxicity)
All
routes/
Cancer
Q1*
of
0.0601
(
Liver
tumors
in
female
mice)

[
Combined
Uncertainty
factors
(
UFs)
for
ETU
occupational
assessments
are
100x;
combined
UFs
for
residential
and
dietary
assessments
are
1000x.
Dermal
absorption
for
ETU
is
26%,
while
inhalation
absorption
is
100%.
Dermal
and
inhalation
exposures
can
be
combined,
since
the
toxic
effects
from
these
two
routes
of
exposure
are
similar
for
similar
durations.]

Dietary
(
Food)
Exposure
Calculation
Methods
and
Residue
Analysis
Crops
treated
with
EBDCs
may
contain
both
EBDC
and
ETU
residues;
in
addition,
cooking
and/
or
processing
may
result
in
conversion
of
EBDC
residues
to
ETU,
or
in
concentration
or
reduction
of
existing
ETU
residues.
Therefore,
both
EBDC
and
ETU
residues
may
be
consumed
in
the
diet.
In
this
assessment
the
ETU
food
residues
from
each
of
the
EBDCs
are
aggregated.
In
some
cases,
these
aggregations
occur
because
the
different
EBDCs
are
used
on
different
crops
which
are
combined
together
to
make
up
the
daily
diet.
In
other
cases
different
EBDCs
are
used
on
the
same
crop
and
the
aggregation
consists
of
adding
some
combination
of
the
ETU
residues
from
each
EBDC.

When
possible,
market
basket
survey
(
MBS)
data,
generated
by
the
ETU
Task
Force,
were
used
to
calculate
anticipated
residues.
Although
the
EBDC/
ETU
MBS
data
were
collected
in
1989/
1990,
the
Agency
has
determined
that
these
data
are
essentially
as
representative
of
EBDC
fungicide
use
today
as
they
were
15
years
ago;
extensive
justification
of
this,
particularly
in
terms
of
minimal
changes
in
percent
crop
treated
(
PCT)
and
application
rates
over
the
years,
has
been
provided.
MBS
data
are
available
on
the
following
foods:
green
beans
(
raw,
frozen,
canned,
and
baby
food),
dry
beans
(
dry
and
canned),
broccoli
(
raw
and
frozen),
celery,
sweet
corn
(
raw,
frozen,
canned),
cucumbers,
lettuce,
meat,
milk,
onion
(
dry
bulb),
potato
(
raw,
frozen),
and
tomato
(
raw,
juice,
ketchup,
paste,
puree).

For
the
probabilistic
acute
dietary
exposure
analysis,
the
entire
distributions
of
residue
data
from
field
trials
or
monitoring
data
were
used
to
generate
residue
distribution
files
(
RDFs)
for
commodities
which
were
considered
to
be
not
blended
or
partially
blended.
For
commodities
considered
to
be
blended
in
this
analysis,
the
average
residues
incorporating
the
likely
maximum
estimated
PCT
was
used
as
a
point
estimate.
The
analysis
for
commodities,
on
which
more
than
one
EBDC
might
be
registered,
different
approaches
were
taken,
depending
upon
the
source
of
the
residue
data.
It
was
assumed
that
commodities
would
not
be
treated
with
more
than
one
EBDC
in
a
season,
as
there
were
not
data
available
to
determine
the
relative
amount
of
crops
treated
with
more
than
one
EBDC.
Only
data
for
the
individual
chemicals
were
available.
When
more
than
one
EBDC
is
registered
on
any
crop
and
the
MBS
data
were
used
for
the
assessment,
4
then
the
percent
crop
treated
values
were
summed
and
an
RDF
was
created
in
which
zeroes
were
added
proportionately.
For
a
few
commodities
mancozeb
field
trial
data
were
used
for
both
mancozeb
and
maneb.
Those
commodities
were
treated
similarly
to
the
commodities
using
MBS.
Individual
field
trial
data
were
used
for
only
two
commodities,
apples
and
grapes,
that
have
registrations
for
more
than
one
EBDC.
RDFs
were
created
with
a
proportionate
number
of
values
from
the
relative
percent
crop
treated
for
each
chemical.
For
example,
the
percent
crop
treated
for
mancozeb,
maneb,
and
metiram
on
apples
is
35,
5,
and
25,
respectively.
Therefore,
an
RDF
where
35%
of
the
values
representing
treated
commodities
were
from
mancozeb
field
trials,
5%
from
maneb
field
trials,
and
25%
from
metiram
field
trials
was
created.

Chronic
anticipated
residues
were
also
calculated
from
field
trial
or
monitoring
data
for
ETU.
Averages
of
the
field
trial
and
MBS
residues
were
used.
In
determining
the
average
residue
when
two
or
more
EBDCs
are
used
on
a
crop,
the
following
equation
was
used.

(
ETU
from
Mancozeb
Residue
x
Mancozeb
PCT/
100)
+
(
ETU
from
Maneb
residue
x
Maneb
PCT/
100)
+
(
ETU
from
Metiram
residue
x
Metiram
PCT/
100)
=
Chronic
AR
for
ETU
If
the
sum
of
the
PCT
values
for
all
three
EBDCs
exceeded
100%
then
the
PCT
values
were
adjusted
so
that
the
sum
equaled
100%.

Drinking
Water
Exposure
The
OPP
Environmental
Fate
and
Effects
Division
(
EFED)
prepared
a
drinking
water
exposure
assessment
for
ETU.
According
to
EFED,
the
parent
EBDC
fungicides
are
very
short­
lived
in
soil
and
water,
and
would
not
reach
water
used
for
human
consumption
whether
from
surface
water
or
ground
water.
However,
ETU
is
highly
water
soluble,
and
may
reach
both
surface
and
ground
water
under
some
conditions.

The
ETU
surface
water
Estimated
Drinking
Water
Concentrations
(
EDWCs)
were
generated
using
a
combined
monitoring/
modeling
approach.
Results
of
a
surface
water
monitoring
study
conducted
by
the
ETU
Task
Force
were
used
to
refine
the
outputs
of
the
PRZM­
EXAMS
models;
the
site/
scenario
modeled
was
application
of
an
EBDC
fungicide
on
peppers
in
FL,
and
was
chosen
to
produce
the
highest
EDWC
acute
values.
The
ground
water
EDWC
was
detected
in
a
FL
community
water
system
intake
in
a
targeted
ground
water
monitoring
study
conducted
by
the
EBDC
task
force
from
1999
to
2003.
Both
these
surface
and
ground
water
values
represent
upper­
bound
conservative
estimates
of
the
total
ETU
residual
concentrations
that
might
be
found
in
surface
water
and
ground
water
due
to
the
use
of
the
EBDC
fungicides.
The
values
are
listed
below:
Acute
Chronic
Cancer
Surface
Water
EDWC
0.1
to
25.2
ppb
0.10
ppb
0.10
ppb
Ground
Water
EDWC
0.21
ppb
0.21
ppb
0.21
ppb
Dietary
Exposure
and
Risk
Analysis
The
acute
dietary
assessment
was
conducted
only
for
females
13­
49
because
this
was
the
only
5
population
subgroup
of
concern
for
acute
effects.
The
NOAEL
of
5
mg/
kg/
day
for
development
defects
was
used
to
establish
the
aPAD
of
0.005
mg/
kg/
day
(
5.0
µ
g/
kg/
day)
by
dividing
it
by
the
uncertainty
factor
of
1000.
The
percent
aPAD
(
55%)
does
not
exceed
100%
at
the
highest
level
of
exposure
(
99.9th
percentile)
which
means
that
the
risks
are
not
of
concern.
The
Critical
Exposure
Contribution
analysis
shows
that
leaf
lettuce
and
turnip
greens
are
major
contributors
to
the
risk
estimates.
When
water
was
added
to
the
dietary
analysis,
the
percent
of
the
aPAD
occupied
was
87%
at
the
99.9
percentile
of
exposure.

The
chronic
dietary
assessment
was
conducted
for
all
populations
because
the
endpoint
of
concern
was
applicable
to
all
populations.
The
NOAEL
of
0.18
mg/
kg/
day
for
thyroid
effects
observed
during
the
chronic
toxicity
study
was
used
to
establish
the
cPAD
of
0.0002
mg/
kg/
day
(
0.2
µ
g/
kg/
day)
by
dividing
it
by
the
uncertainty
factor
of
1000.
Estimated
chronic
dietary
exposures
for
all
population
subgroups
occupied
<
54%
of
the
chronic
Population
Adjusted
Dose
(
cPAD)
and
are
below
HED's
level
of
concern.
In
the
chronic
aggregate
(
food
and
water)
assessment,
the
highest
exposed
population
subgroup
was
children
(
1
to
2
years
old)
which
occupied
56
to
58%
of
the
cPAD.

The
dietary
cancer
risk
from
food
alone
was
estimated
for
the
general
U.
S.
population
and
was
1.9
x
10­
6.
The
commodity
contribution
analysis
indicates
that
apple
juice
and
leaf
lettuce
are
the
major
contributors
to
the
risk
estimates.
Cancer
risk
estimates
aggregating
food
and
water
ranged
from
2.0
x
10­
6
to
2.1
x
10­
6.

Residential
and
Recreational
Exposures
and
Risks
There
is
a
potential
for
home
gardener
exposure
during
and
after
applications
to
home
garden
vegetables.
There
is
also
a
potential
for
golfer,
athlete
and
toddler
post
application
exposure
on
golf
course
turf,
athletic
fields
and
transplanted
lawns.
As
a
result,
risk
assessments
have
been
completed
for
both
residential
handler
and
postapplication
scenarios.

The
agricultural
application
rates
were
used
because
the
rates
given
on
the
two
home
garden
product
labels
appeared
to
have
conflicts
with
each
other
and
were
generally
higher
than
the
agricultural
rates.
The
residential
handler
Margins
of
Exposure
(
MOEs)
for
both
mancozeb
and
ETU
were
not
of
concern
because
they
greatly
exceeded
the
target
MOEs
of
100
and
1000,
respectively.
The
cancer
risks
were
also
not
of
concern
because
they
are
less
than
1x10­
6
.

The
post
application
risks
were
also
assessed
for
adult
and
youth­
aged
home
gardeners
working
in
gardens
following
mancozeb
treatment.
The
ETU
MOEs
exceeded
the
target
MOE
of
1000
for
both
adult
and
youth
home
gardeners.
The
cancer
risk
for
adult
home
gardeners
was
less
than
1x10­
6
.

The
turf
exposures
were
assessed
for
toddlers
by
assuming
that
the
turf
would
be
installed
in
a
residential
setting
no
sooner
than
three
days
after
application.
The
three
days
includes
the
existing
Pre­
Harvest
Interval
(
PHI)
of
one
day
and
two
days
to
harvest,
transport
and
install
the
turf.
The
individual
MOEs
were
all
above
the
target
MOEs
with
the
exception
of
the
dermal
MOE
for
ETU
from
maneb.
The
total
MOEs
which
included
dermal,
hand­
to­
mouth,
object
to
mouth
and
soil
6
ingestion
were
also
below
1000
at
the
existing
PHI
of
1
day.
The
individual
MOEs
rise
to
1000
a
PHI
of
1
to
3
days
while
the
total
MOEs
rise
to
1000
with
a
PHI
of
3
days.

The
turf
exposures
were
assessed
for
golfers
and
athletes
by
using
the
day
0
Turf
Transferable
Residues
(
TTR)
for
short
term
exposures
and
the
7
day
average
TTR
for
lifetime
exposures.
The
ETU
MOE
for
golfers
exceeded
the
target
MOE
of
1000
while
the
ETU
MOE
for
athletes
(
450)
did
not
exceed
the
target
MOE.
The
golfer
cancer
risk
was
6
x
10­
9
assuming
that
golfers
played
an
average
of
1
day
per
year
on
mancozeb
treated
turf.
The
cancer
risk
for
athletes
was
6
x
10­
8
assuming
1
day
exposure
per
year
on
mancozeb
treated
turf
and
10
years
exposure
per
lifetime.

Aggregate
Risks
The
aggregate
exposures
for
adults
included
food,
drinking
water,
golfing,
and
home
gardening
while
the
aggregate
exposures
for
toddlers
include
only
food
and
water.
The
toddler's
exposures
to
treated
turf
is
likely
to
be
a
rare
scenario
so
it
is
not
appropriate
to
aggregate.
The
adult
recreational,
food,
and
water
exposures
were
only
aggregated
for
short
term
and
cancer
risks
because
they
consisted
of
a
series
of
short
term
exposures
that
occur
year
after
year.
The
acute
and
chronic
risks
were
aggregated
only
for
food
and
water.

Acute
aggregate
risks
were
calculated
for
females
13­
49
only
because
the
acute
endpoint
was
based
upon
developmental
effects
which
were
only
applicable
to
this
population
subgroup.
The
acute
aggregate
exposures
were
not
of
concern
because
the
exposure
was
87%
of
the
aPAD
at
the
99.9th
percentile
of
exposure.
The
short
term
aggregate
risks
were
calculated
for
adults
by
aggregating
chronic
food
exposure,
chronic
drinking
water
exposure
and
the
residential
exposures.
The
short
term
risks
were
calculated
for
the
most
sensitive
adult
population
(
females
13­
49)
because
the
endpoint
is
based
upon
developmental
effects.
The
MOE
ranged
from
4500
to
62000
which
indicates
that
the
risks
are
not
of
concern.

The
chronic
aggregate
risks
were
calculated
using
food
and
water
exposure
and
were
below
HED's
level
of
concern
(
100%
cPAD).
The
most
highly
exposed
population
subgroup
is
children
1­
2
years
old,
with
aggregate
risks
of
56­
58
%
cPAD.
Exposure
from
food
was
an
order
of
magnitude
greater
than
exposure
from
drinking
water.

The
cancer
risks
were
aggregated
using
the
food,
drinking
water
and
residential/
recreational
exposures.
The
aggregate
doses
were
multiplied
by
the
ETU
Q
1
*
of
0.0601
(
mg/
kg/
day)­
1
to
determine
the
cancer
risks.
These
risks
range
from
2.1
x
10­
6
to
2.8
x
10­
6
depending
upon
the
drinking
water
source
and
the
type
of
residential
exposure.
The
food
exposure
is
the
largest
source
of
the
cancer
risk
(
1.9
x
10­
6)
followed
by
drinking
water
from
groundwater
sources
(
2.7
x
10­
7).

The
food
risks
are
somewhat
conservative
because
the
anticipated
residues
for
several
of
the
commodities
are
based
upon
field
trial
data
or
poor
quality
residue
data.
The
residue
data
for
the
greatest
single
contributor,
leaf
lettuce,
are
based
on
field
trial
studies
Field
trial
data
are
conservative
as
they
represent
residues
at
harvest
as
opposed
to
residues
at
the
time
of
consumption.
For
maneb,
the
adequacy
of
the
residue
data
to
support
tolerances
are
poor
for
crops
such
as
apple,
grape
and
lettuce.
In
all
of
these
cases,
either
extrapolation
to
the
label
use
7
N
H
NH
S
pattern
or
use
of
mancozeb
field
trial
data
were
necessary
to
estimate
maneb
and
ETU
dietary
exposure.
Although
studies
are
available
to
determine
the
loss
of
ETU
and
conversion
of
EBDC
to
ETU
upon
cooking
and
certain
processing
steps,
little
data
are
available
to
ascertain
the
degree
of
physical
ETU
removal
during
washing,
peeling,
etc.
As
a
result,
many
ETU
estimates
are
expected
to
be
somewhat
conservative
even
though
the
majority
of
ETU
residues
are
not
likely
to
be
on
the
surface
of
foods.
The
generation
of
additional
market
basket
survey
data
to
be
used
in
dietary
exposure
assessments
to
replace
the
field
trial
data
used
for
numerous
crops
would
permit
additional
refinements,
particularly
for
the
greatest
contributor
to
estimated
exposure,
leaf
lettuce.
The
risks
for
toddlers
exposed
to
treated
sod
farm
turf
was
calculated
because
it
was
thought
that
some
exposure
could
occur
after
this
turf
was
installed
in
a
residential
setting.
To
partially
account
for
the
fact
that
transplanted
turf
requires
substantial
irrigation
to
become
established,
the
TTR
data
from
the
California
site,
which
received
2.5
inches
of
irrigation
during
the
study
period,
was
used
to
determine
the
dissipation
rate.
Given
that
transplanted
turf
would
typically
be
irrigated
at
a
higher
rate,
the
toddler
risks
can
be
considered
to
be
upper
bound
estimates.

Occupational
Exposures
Assessments
for
occupational
exposures
have
been
conducted
for
each
EBDC,
and
in
each
of
these
assessments
the
risks
of
the
parent
EBDC
and
the
degradate
ETU
have
been
considered.
With
the
exception
of
chronic
ETU
exposures,
the
risks
of
exposure
to
the
parent
EBDCs
were
generally
greater
than
the
risks
of
exposure
to
ETU.
If
some
combination
of
maneb,
mancozeb
and
metiram
were
used
the
resulting
risk
would
fall
between
3.6
x
10­
7
and
1.8
x
10­
5.
Although
the
assumption
could
be
made
that
the
aggregate
ETU
cancer
risk
would
be
the
sum
of
the
risks
for
mancozeb,
maneb
and
metiram,
this
assumption
might
not
be
valid
because
the
use
data
indicate
that
there
is
limited
overlap
in
use
patterns.

2.0
Physical/
Chemical
Properties
Technical
ethylene
thiourea
(
ETU)
is
a
crystalline
solid
with
a
white
to
pale
green
color,
and
a
faint
amine
odor.
It
has
a
melting
point
of
203­
204
C.
ETU
has
an
octanol/
water
partition
coefficient
of
0.22.
ETU
is
considered
soluble
in
water,
with
a
water
solubility
of
20,000
ppm
at
30
C,
but
it
is
also
slightly
soluble
in
methanol,
ethanol,
ethylene
glycol,
pyridine,
acetic
acid
and
naphtha.
When
ETU
is
heated
to
decomposition,
nitrogen
and
sulfur
oxides
are
emitted.

Empirical
Formula:
C
3
H
6
N
2
S
Molecular
Weight:
102.2
CAS
Registry
No.:
96­
45­
7
PC
Code:
600016
The
structure
of
ETU
is
as
follows:
8
3.0
Hazard
Characterization
3.1
Hazard
Profile
The
database
for
ETU
is
limited.
Of
nine
submitted
studies
evaluated
by
the
Hazard
Identification
Assessment
Review
Committee
(
HIARC),
three
studies
were
unacceptable
because
ETU
concentrations
in
feed
varied
widely
and
two
other
studies
had
only
one
dose
group.
The
HIARC
(
5/
28/
03,
TXR
#
0051924)
named
the
following
studies
as
data
gaps:
developmental
toxicity
study
in
rabbits,
2­
generation
reproduction
toxicity
in
rats,
comparative
study
for
thyroid
toxicity
in
adults
and
offspring,
and
a
developmental
neurotoxicity
study.

The
thyroid
is
a
target
organ
for
ETU
as
it
is
for
the
EBDC
fungicides.
Thyroid
toxicity
in
subchronic
and
chronic
rat,
mouse,
and
dog
studies
included
decreased
levels
of
the
thyroid
hormone,
T4,
increases
or
decreases
in
the
thyroid
hormone,
T3,
compensatory
increases
in
levels
of
thyroid
stimulating
hormone
(
TSH),
increased
thyroid
weight,
and
microscopic
thyroid
changes,
chiefly
hyperplasia.

Anemia
occurred
in
the
subchronic
and
chronic
dog
studies.
Increased
liver
weight
and
hepatocellular
hypertrophy
occurred
in
several
studies;
however,
overt
liver
toxicity
was
limited
to
the
chronic
dog
study
in
which
hepatocellular
necrosis
was
seen.

Developmental
defects
in
the
rat
developmental
study
indicated
increased
qualitative
susceptibility
since
numerous,
severe
developmental
defects
occurred
at
a
dose
which
only
caused
decreased
maternal
food
consumption
and
body
weight
gain.
These
developmental
defects
were
similar
to
defects
seen
in
an
accompanying
developmental
toxicity
study
with
mancozeb;
however,
ETU
was
considered
a
more
severe
developmental
toxicant
than
mancozeb
because:
(
a)
a
smaller
dose
of
ETU
(
50
mg/
kg/
day)
was
needed
to
cause
developmental
defects
than
did
mancozeb
(
512
mg/
kg/
day);
(
b)
many
of
the
same
developmental
defects
occurred
with
greater
frequency
with
ETU
than
with
mancozeb;
(
c)
more
types
of
developmental
defects
occurred
with
ETU
than
with
mancozeb;
and
(
d)
developmental
defects
which
occurred
with
ETU
were
accompanied
by
minimal
maternal
toxicity
whereas
developmental
defects
that
occurred
with
mancozeb
were
accompanied
by
more
severe
maternal
toxicity.

The
developmental
defects
seen
in
the
rat
developmental
study
with
ETU
included
exencephaly,
atrophy
of
brain
tissue,
cranial
edema,
dilated
ventricles
of
the
brain,
compression
and/
or
hemorrhages
of
the
spinal
cord,
deficiency
of
tissue
in
the
olfactory
bulb,
meningoencephalocele
,
incomplete
cranial
ossification,
wide
cranial
sutures,
curved
clavicle,
fused
sternebrae,
absent
caudal
or
sacral
vertebrae,
fused
and/
or
thickened
ribs,
wavy
ribs,
misshapen
or
incomplete
ossification
of
hindlimb
long
bones,
ribs
and
pelvis,
kyphosis
(
abnormal
spine
curvature),
reduced
number
of
ribs,
fused
lumbar,
sacral,
or
caudal
vertebrae,
abnormal
pelvic
limb
posture,
oligodactyl,
agnathia,
cleft
palate,
cleft
lip,
club
limb,
stubby
tail,
forelimb
flexure,
kinked
tail,
cryptorchidism
(
abnormal
descending
of
the
testes),
ectopic
kidneys,
agenesis
of
the
kidneys,
hydronephrosis,
reduced
stomach
with
thickened
wall,
edematous
fat
pads,
syndactyl
digits,
and
anal
atresia
(
closure).
9
A
developmental
study
in
rabbits
was
not
submitted.
No
reproductive
toxicity
was
attributed
to
treatment
in
the
2­
generation
reproduction
study
in
rats.
Neurotoxicity
studies
with
ETU
were
not
available.

Treatment
with
ETU
produced
increases
in
tumor
incidence
in
rodents.
Thyroid
follicular
cell
adenomas
and
carcinomas
were
increased
in
a
study
with
F344
rats.
Thyroid
follicular
cell
adenomas
and
pituitary
adenomas
were
increased
in
a
study
with
SD
rats.
Thyroid
follicular
cell
adenomas
and
carcinomas,
hepatocellular
adenomas
and
carcinomas,
and
pituitary
adenomas
were
increased
in
a
study
with
B6C3F1
mice.

The
HED
Cancer
Assessment
Review
Committee
evaluated
the
carcinogenicity
potential
of
ETU
and
classified
ETU
as
a
group
B2
probable
human
carcinogen
(
Bill
Sette,
Ph.
D.,
4/
16/
90).
The
cancer
potency
factor,
or
Q
1
*,
for
ETU,
using
a
3/
4
scaling
factor,
was
determined
to
be
6.01
x
10­
2
mg/
kg/
day­
1
based
upon
female
mouse
liver
tumors
in
an
National
Toxicology
Program
(
NTP)
study
(
Bernice
Fisher
and
Hugh
Pettigrew,
2/
24/
95).
The
Q
1
*
for
ETU
is
also
used
for
the
EBDC
compounds,
mancozeb,
metiram,
and
maneb
which
are
metabolized
to
ETU
(
HED
Doc.
No.
013554,
7/
7/
99).

Acute
toxicity
information
and
a
toxicity
profile
are
shown
in
Tables
3.1
and
3.2.
Acute
oral
and
dermal
sensitization
studies
with
ETU
were
not
available.

Table
3.1.
Acute
Toxicity
of
ETU
Guideline
No.
Study
Type
MRID
Nos.
Results
Toxicity
Category
870.1100
Acute
Oral
­
rat
N/
A
N/
A
N/
A
870.1200
Acute
Dermal
­
rabbit
458881­
01
LD50
>
2000
mg/
kg
III
870.1300
Acute
Inhalation
­
rat
458881­
02
LC50
>
10.4
mg/
L
IV
870.2400
Primary
Eye
Irritation
458881­
04
No
irritation
a
IV
870.2500
Primary
Skin
Irritation
458881­
03
No
irritation
IV
870.2600
Dermal
Sensitization
N/
A
N/
A
N/
A
a
The
primary
eye
irritation
study
was
classified
unacceptable
because
a
UV
light
was
not
observed
with
fluorescein
staining,
however,
another
study
is
not
required
(
M.
Lewis,
4/
30/
03,
D289726).
10
Table
3.2
continued
on
following
page
Table
3.2.
ETU
Toxicity
Profile
Study
Type
[
Guideline
No.]
MRID
No./
Year
Classification
Results
Subchronic
(
13­
week)
feeding
­
rat
[
870.3100]
00261536/
1986
Unacceptable
NOAEL
=
<
14.28
mg/
kg/
day
LOAEL
=
14.28
mg/
kg/
day,
based
on
reduced
body
wt,
changes
in
thyroid
hormone
and
TSH
levels,
increased
thyroid
and
liver
wt,
microscopic
thyroid
hyperplasia
and
liver
hypertrophy.

Subchronic
(
13­
Week)
feeding
­
mouse
[
870.3100]
00259888/
1985
Unacceptable
NOAEL
=
1.72
mg/
kg/
day
LOAEL
=
18.18
mg/
kg/
day,
based
on
microscopic
thyroid
hypertrophy/
hyperplasia
%
purity,
feed
concentrations
were
not
reported.
At
the
high
dose,
more
microscopic
thyroid
changes
and
increases
in
thyroid
and
liver
wt
occurred.

Subchronic
(
13­
Week)
feeding
­
dog
[
870.3100]
42174201/
1991
NOAEL
=
0.39
mg/
kg/
day
LOAEL
=
6.02
mg/
kg/
day,
based
on
elevated
cholesterol.

In
high
dose
group:
mortality,
anemia,
decreased
activity,
decreased
thyroid
hormone
levels,
increased
thyroid
wt,
microscopic
thyroid
hyperplasia
Chronic
tox/
carcinogenicity
­
rat
[
870.4100]
42607801/
1992
Unacceptable
Concentration
of
ETU
in
feed
varied
widely
and
doses
could
not
be
determined.

Microscopic
thyroid
hyperplasia
occurred
in
the
low­
dose
group.
At
higher
doses,
changes
in
thyroid
hormone
and
TSH
levels,
increased
thyroid
wt,
and
grossly
enlarged
livers,
occurred.
Increases
in
thyroid
follicular
adenomas
and
pituitary
adenomas
in
high­
dose
males.

Chronic
(
24­
Month)
Feeding
­
mouse
(
NTP)
This
study
was
used
to
determine
the
Q1*
for
ETU
of
6.01
x
10­
2
(
mg/
kg/
day)­
1
based
upon
female
mouse
liver
adenomas
and/
or
carcinomas.

Chronic
(
1­
yr)
oral
toxicity
­
dog
[
870.4100]
42338101/
1992
NOAEL
=
0.18
mg/
kg/
day
LOAEL
=
1.79
mg/
kg/
day,
based
on
increased
thyroid
wt
and
microscopic
changes
in
thyroid
(
hypertrophy,
follicular
dilatation).

At
the
high
dose,
mortality,
anemia,
and
microscopic
hepatocellular
necrosis.

4­
Week
Rangefinding
­
dog
41863401/
1989
NOAEL
=
7
mg/
kg/
day
LOAEL
=
34
mg/
kg/
day,
based
on
decreased
levels
of
thyroid
hormones,
gross
thyroid
lesions.
Table
3.2.
ETU
Toxicity
Profile
Study
Type
[
Guideline
No.]
MRID
No./
Year
Classification
Results
11
Developmental
tox.
­
rat
[
870.3700]
00246663/
1980
Unacceptable
Maternal
NOAEL
=
<
50
mg/
kg/
day
Maternal
LOAEL
=
50
mg/
kg/
day,
based
on
decreased
body
weight
gain
Developmental
NOAEL
=
<
50
mg/
kg/
day
Developmental
LOAEL
=
50
mg/
kg/
day,
based
on
gross
developmental
defects,
central
nervous
system
defects,
skeletal
defects,
cryptorchidism,
and
decreased
fetal
weight.

[
Only
one
dose
group
was
included
in
the
study.]

Developmental
tox.
­
rat
[
870.3700]
4593760/
1973
[
Khera,
K.
S..
1973.
Teratology
7:
243­
252]
Maternal
NOAEL
=
40
mg/
kg/
day
Maternal
LOAEL
=
80
mg/
kg/
day,
based
on
mortality.

Developmental
NOAEL
=
5
mg/
kg/
day
Developmental
LOAEL
=
10
mg/
kg/
day
based
on
central
nervous
system
and
gross
developmental
defects.

2­
Generation
reproduction
­
rat
[
870.3800]
42391701/
1992
Unacceptable
Doses
on
a
mg/
kg/
day
basis
could
not
be
determined.

Parental:
microscopic
thyroid
hyperplasia/
hypertrophy
in
midand
or
high­
dose
groups.

No
reproductive
effects
attributed
to
treatment.

Dermal
absorption
­
rat
[
870.7600]
40312001/
1987
Dermal
absorption
=
26%

3.2
FQPA
Considerations
On
February
20,
2003,
the
HED
HIARC
evaluated
the
toxicology
database
for
ETU,
and
reviewed
the
potential
for
increased
susceptibility
of
infants
and
children
from
exposure
to
ETU
in
accordance
with
the
February
2002
OPP
10X
guidance
document.
Studies
available
for
FQPA
consideration
included
several
developmental
toxicity
studies
from
the
literature,
one
unacceptable
guideline
developmental
toxicity
study
in
which
only
one
dose
was
administered,
and
a
2­
generation
reproduction
toxicity
study
in
rats.

The
HIARC
concluded
there
is
concern
for
prenatal
toxicity
resulting
from
exposure
to
ETU
because
of
effects
seen
in
developmental
studies.
There
was
evidence
of
quantitative
and
qualitative
susceptibility
to
fetuses
in
several
developmental
studies
in
rats:

(
1)
In
a
1973
literature
study
(
Khera),
developmental
defects
of
the
brain
in
the
fetuses
occurred
at
a
dose
significantly
lower
than
the
dose
at
which
maternal
toxicity
was
observed;
12
(
2)
In
a
1979
literature
study
(
Chernoff,
et.
al.),
the
maternal
toxicity
NOAEL
was
twice
the
developmental
LOAEL,
at
which
hydrocephalus
occurred.
The
maternal
LOAEL
was
four
times
higher
than
the
developmental
LOAEL,
and
the
effect
consisted
of
reduced
body
weight
gain
and
mortality;

(
3)
In
a
1978
literature
study
(
Teramoto,
et.
al.),
developmental
toxicity
(
dilated
ventricle
of
the
brain
was
seen
at
the
lowest
dose
tested
(
10
mg/
kg/
day)
in
the
absence
of
maternal
toxicity;

(
4)
In
a
1991
literature
study
(
Saillenfait,
et.
al.),
severe
developmental
effects
(
dilated
ventricles
of
the
brain,
hydroureter,
short/
kinky
tail,
and
dilated
ureters)
were
seen
at
a
dose
(
25
mg/
kg/
day)
that
only
induced
decreases
in
body
weight
gain
in
the
dams.

Evidence
of
susceptibility
in
rabbits
could
not
be
ascertained
due
to
the
datagap
for
a
prenatal
study
in
this
species.
The
2­
generation
reproduction
study
in
rats
was
not
adequate
to
evaluate
susceptibility.

Since
there
is
evidence
of
increased
susceptibility
of
fetuses
following
exposure
to
ETU
in
the
rat
developmental
studies,
HIARC
evaluated
the
level
of
concern
for
the
effects
observed
when
considered
in
the
context
of
all
available
toxicity
data.
In
addition,
HIARC
evaluated
the
database
to
determine
if
there
were
residual
uncertainties
after
establishing
toxicity
endpoints
and
traditional
uncertainty
factors
to
be
used
in
the
EBDC
and
ETU
risk
assessment.
HIARC
determined
that
the
degree
of
concern
for
the
susceptibility
seen
in
ETU
developmental
studies
was
low
because:

C
The
teratogenic
effects
have
been
well­
characterized
in
numerous
studies
in
the
published
literature,
as
well
as
in
a
guideline
study
submitted
by
the
registrant;

C
There
is
a
clear
NOAEL
for
these
effects
and
the
dose­
response
relationship,
although
steep,
is
well
characterized
in
the
numerous
developmental
studies
in
rats.

C
The
developmental
endpoint
with
the
lowest
NOAEL
was
selected
for
deriving
the
acute
RfD.

C
The
target
organ
toxicity
(
thyroid
toxicity)
was
selected
for
deriving
the
chronic
RfD
as
well
as
endpoints
for
non­
dietary
exposures
(
incidental
oral,
dermal,
and
inhalation).

Since
the
ETU
doses
selected
for
overall
risk
assessments
will
address
the
concern
for
developmental
and
thyroid
toxicity,
there
are
no
residual
uncertainties
with
regard
to
pre­
and/
or
post­
natal
toxicity.
The
HIARC
concluded
that
the
special
FQPA
Safety
Factor
(
SF)
could
be
removed
(
reduced
to
1X)
for
ETU.

The
HIARC
concluded
a
developmental
neurotoxicity
study
for
ETU
is
required,
based
on
severe
central
nervous
system
defects
observed
in
the
developmental
toxicity
study
in
rats,
including
exencephaly,
atrophy
of
brain
tissue,
cranial
edema,
dilated
ventricles
of
the
brain,
compression
and/
or
hemorrhages
of
the
spinal
cord,
deficiency
of
tissue
in
the
olfactory
bulb,
and
meningoencephalocele.
In
addition
to
the
developmental
neurotoxicity
study,
the
following
data
gaps
were
identified:
13
C
Developmental
toxicity
study
in
rabbits
C
2­
Generation
reproduction
study
in
rats
C
A
study
evaluating
the
comparative
thyroid
toxicity
in
adults
and
offspring
The
HIARC
determined
that
a
10x
database
uncertainty
factor
(
UF
DB
)
is
needed
to
account
for
the
lack
of
these
studies
since
the
available
data
provide
no
basis
to
support
reduction
or
removal
of
the
default
10x
factor.

3.3
Dose
Response
Assessment
The
HIARC
evaluated
the
toxicology
database
of
ETU
on
February
20,
2003
and
selected
the
doses
and
endpoints
for
risk
assessment
based
on
a
variety
of
exposure
pathways
resulting
from
use
of
the
EBDC
fungicides.
These
doses
and
endpoints
are
listed
in
Table
3.3.

3.3.1
ETU
Acute
Dietary
Endpoint
The
ETU
acute
dietary
endpoint
for
females
13
­
49
years
old
was
selected
from
a
non­
guideline
developmental
toxicity
study
in
rats
(
Khera,
K.
S.;
Teratology
7:
243­
252,
1973,
MRID
No.
4593760).
The
LOAEL
was
10
mg/
kg/
day
based
on
developmental
effects
of
the
brain,
including
exencephaly,
dilated
ventricles,
and
hypoplastic
cerbellum.
The
NOAEL
for
the
study
was
5
mg/
kg/
day.
Application
of
the
combined
standard
10X
UFs
to
account
for
intraspecies
variability
and
interspecies
extrapolation,
and
the
10X
UF
DB
,
results
in
an
acute
reference
dose
(
aRfD)
of
0.005
mg/
kg/
day.
The
acute
population
adjusted
dose
(
aPAD)
reflects
incorporation
of
the
Special
FQPA
SF
into
the
RfD.
Since
the
Special
FQPA
SF
was
removed
(
reduced
to
1X)
for
ETU,
the
aPAD
is
equivalent
to
the
aRfD,
0.005
mg/
kg/
day.

The
ETU
acute
dietary
endpoint
applies
only
to
females
13­
49
years
old,
but
is
protective
of
the
general
population
including
infants
and
children.
No
endpoint
attributed
to
a
single
dose
was
identified
for
the
general
population
in
the
other
available
toxicity
studies.

3.3.2
ETU
Chronic
Dietary
Endpoint
HIARC
selected
the
ETU
chronic
dietary
endpoint
from
a
chronic
toxicity
study
in
dogs.
The
study
NOAEL
was
0.18
mg/
kg/
day
based
on
decreased
body
weight
gain,
increased
thyroid
weight,
and
microscopic
changes
in
the
thyroid
observed
at
the
LOAEL
of
1.99
mg/
kg/
day.
The
combined
1000X
UF
(
standard
100X
and
an
additional
10X
UF
DB
)
results
in
a
chronic
reference
dose,
RfD,
of
0.0002
mg/
kg/
day.
The
cPAD
of
0.0002
mg/
kg/
day
is
the
same
as
the
RfD,
since
the
Special
FQPA
SF
was
reduced
to
1X.
14
3.3.3
ETU
Incidental
Oral
Exposure
(
Short­
and
Intermediate­
Term)
Endpoints;
ETU
Aggregate
Children
(
Short­
and
Intermediate­
Term)
Endpoints
A
non­
guideline
4­
week
range­
finding
toxicity
study
conducted
in
dogs
was
used
to
select
incidental
oral
endpoints
and
doses
for
risk
assessment.
In
addition,
the
HIARC
concluded
that
short­
and
intermediate­
term
aggregate
exposures,
combining
dietary,
incidental
oral,
dermal
and
inhalation
pathways,
should
be
compared
to
this
endpoint
and
NOAEL
for
risk
assessment.
The
study
NOAEL
was
7
mg/
kg/
day
based
on
gross
thyroid
lesions
and
decreased
thyroid
hormone
levels
at
the
LOAEL
of
34
mg/
kg/
day.
The
endpoint
is
appropriate
for
the
population
(
infants/
children)
and
duration
of
exposure
(
up
to
30
days);
in
addition,
the
study
can
be
used
for
intermediate­
term
incidental
oral
risk
assessment,
since
it
is
supported
by
a
subchronic
toxicity
study
in
dogs
in
which
the
NOAEL
for
thyroid
effects
was
similar,
at
6
mg/
kg/
day.
The
combined
UF
applied
to
both
short­
and
intermediate­
term
incidental
oral
risk
assessments
is
1000X,
based
on
the
standard
100X
UF,
as
well
as
a
10X
UF
DB
.
An
additional
UF
to
extrapolate
from
a
shorter­
to
a
longer­
term
study
was
not
needed,
since
the
NOAEL
for
thyroid
effects
in
the
subchronic
dog
study
was
similar
to
that
observed
in
the
4­
week
dog
study.

3.3.4
ETU
Dermal
Absorption
The
ETU
dermal
absorption
factor
is
26%,
from
a
dermal
absorption
study
in
rats.
The
value
of
26%
dermal
absorption
was
determined
at
the
lowest
dermal
dose
after
10
hours
of
exposure
followed
by
washing
of
the
skin.
ETU
residues
were
detected
in
organs
at
all
3
dermal
doses,
and
were
highest
in
the
thyroid.

3.3.5
ETU
Dermal
Exposure
(
Short­
and
Intermediate­
Term)
Endpoints;
ETU
Inhalation
Exposure
(
Short­
and
Intermediate­
Term)
Endpoints;
ETU
Aggregate
Females
13­
49
(
Short
and
Intermediate­
Term)
Endpoints
In
the
absence
of
adequate
dermal
and
inhalation
toxicity
studies
for
ETU,
the
non­
guideline
oral
study
in
rats
(
Khera)
was
used
to
select
endpoints
for
short­
and
intermediate­
term
dermal
and
inhalation
risk
assessments.
The
study
NOAEL
was
5
mg/
kg/
day
based
on
developmental
effects
of
the
brain,
including
exencephaly,
dilated
ventricles,
and
hypoplastic
cerbellum,
observed
at
the
LOAEL
of
10
mg/
kg/
day;
the
endpoint
is
considered
applicable
for
females
13
­
50
years
old.

Because
an
oral
toxicity
study
was
chosen,
the
26%
dermal
absorption
factor
for
ETU
should
be
used
in
the
dermal
exposure
assessment,
and
100%
absorption
should
be
assumed
for
calculating
inhalation
exposure
and
risk.
The
target
MOE
for
residential
exposures
is
1000,
which
includes
the
standard
100X
combined
UF,
as
well
as
the
10X
UF
DB
for
an
incomplete
database.
The
target
MOE
for
occupational
assessments
is
100.

The
HIARC
recommended
that
short­
and
intermediate­
term
aggregate
risk
assessments
for
the
population
females
13­
49
be
calculated
by
comparing
aggregate
exposure
(
dietary,
dermal,
and
inhalation)
to
the
NOAEL
from
the
developmental
toxicity
study
in
rats.
The
endpoint
is
considered
relevant
for
the
population
(
females
13
­
50)
and
duration
of
exposure.
15
Table
3.3
Continued
on
following
page
3.3.6
ETU
Dermal
Exposure
(
Long­
Term
)
Endpoint;
ETU
Inhalation
Exposure
(
Long­
Term)
Endpoint
The
HIARC
selected
long­
term
dermal
and
inhalation
endpoints
from
the
chronic
toxicity
study
in
dogs.
The
NOAEL
is
0.18
mg/
kg/
day
based
on
decreased
body
weight
gain,
increased
thyroid
weight,
and
microscopic
changes
in
the
thyroid
at
the
LOAEL
of
1.99
mg/
kg/
day.
Since
an
oral
study
was
selected,
estimated
dermal
exposure
should
be
adjusted
by
26%,
the
ETU
dermal
absorption
factor.
For
calculating
inhalation
risks,
a
100%
absorption
factor
should
be
used.
For
residential
exposures,
the
target
MOE
for
ETU
is
1000,
based
on
the
combined
UFs
of
100X
for
intra­
species
variability
and
interspecies
extrapolation,
and
an
additional
10X
UF
DB
for
an
incomplete
database.
For
occupational
exposures,
the
long­
term
target
MOE
for
dermal
and
inhalation
exposures
is
100.

Table
3.3.
ETU
Toxicological
Doses
and
Endpoints
for
Use
in
Human
Health
Risk
Assessment
Exposure
Scenario
Dose
Used
in
Risk
Assessment
and
UFs
Special
FQPA
SF
and
Endpoint
for
Risk
Assessment
Study
and
Toxicological
Effects
ETU
Dietary
Exposures
Acute
Dietary
Females
13
­
50
NOAEL
=
5
mg/
kg/
day
UF
=
100X
(
inter
and
intraspecies)
UF
=
10Xdatabase
Total
UF
=
1000X
Acute
RfD
=
0.005
mg/
kg/
day
Special
FQPA
SF
=
1X
aPAD
=
Acute
RfD
FQPA
SF
aPAD
=
0.005
mg/
kg/
day
Developmental
Rat
Toxicity
(
Khera
Study,
MRID
459376­
01)
LOAEL
=
10
mg/
kg/
day,
based
on
developmental
defects
of
brain.

Acute
Dietary
General
Population
Not
Applicable
No
appropriate
endpoint
attributable
to
a
single
exposure
(
dose)
was
identified.

Chronic
Dietary
NOAEL
=
0.18
mg/
kg/
day
UF=
100X
(
inter
and
intraspecies)
UF
=
10Xdatabase
Total
UF
=
1000X
Chronic
RfD=
0.0002
mg/
kg/
day
Special
FQPA
SF
=
1X
cPAD
=
Chronic
RfD
FQPA
SF
cPAD
=
0.0002
mg/
kg/
day
Dog
Chronic
Oral
Toxicity
MRID
No.
LOAEL=
1.99
mg/
kg/
day
based
on
thyroid
toxicity
Cancer
[
oral/
dermal/
inhalati
on]
Q1*
=
6.01x10­
2
(
mg/
kg/
day)­
1
ETU
is
classified
as
a
Group
B2
carcinogen
with
a
low­
dose
extrapolation
approach
for
human
risk
assessment,
based
on
liver
tumors
in
female
mice
ETU
Incidental
Oral
Exposures
[
Residential/
Postapplication]
Table
3.3.
ETU
Toxicological
Doses
and
Endpoints
for
Use
in
Human
Health
Risk
Assessment
Exposure
Scenario
Dose
Used
in
Risk
Assessment
and
UFs
Special
FQPA
SF
and
Endpoint
for
Risk
Assessment
Study
and
Toxicological
Effects
16
Short­
Term
[
1­
30
days]

Intermediate­
Term
[>
30
days
to
6
months]
NOAEL
=
7
mg/
kg/
day
UF
=
100X
(
inter
and
intraspecies)
UF
=
10Xdatabase
Total
UF
=
1000X
Special
FQPA
SF
=
1X
Residential
MOE
=
1000
Occupational
MOE
=
N/
A
4­
week
range­
finding
dog
study
LOAEL=
34
mg/
kg/
day
based
thyroid
toxicity
ETU
Dermal
Exposures
Short­
Term
[
1­
30
days]
Females
13­
49
Intermediate­
Term
[
30
days
­
6
months]
NOAEL
=
5
mg/
kg/
day
UF
=
100X
(
inter
and
intraspecies)
UF
=
10Xdatabase
Dermal
Absorption
=
26%
Special
FQPA
SF
=
1X
Residential
MOE
=
1000
Occupational
MOE
=
100
Same
as
above
for
acute
dietary
exposures.

Long­
Term
[>
6
months]
NOAEL
=
0.18
mg/
kg/
day
UF
=
100X
(
inter
and
intraspecies)
UF
=
10Xdatabase
Derma
Absorption
=
26%
Special
FQPA
SF
=
1X
Residential
MOE
=
1000
Occupational
MOE
=
100
Same
as
above
for
chronic
dietary
exposures.

ETU
Inhalation
Exposures
Short­
Term
[
1­
30
days]
Females
13­
49
Intermediate­
Term
[
30
days
­
6
months]
NOAEL
=
5
mg/
kg/
day
UF
=
100X
(
inter
and
intraspecies)
UF
=
10Xdatabase
Inhalation
Absorption
=
100%
Special
FQPA
SF
=
1X
Residential
MOE
=
1000
Occupational
MOE
=
100
Same
as
above
for
acute
dietary
exposures.

Long­
Term
[>
6
months]
NOAEL
=
0.18
mg/
kg/
day
UF
=
100X
(
inter
and
intraspecies)
UF
=
10Xdatabase
Inhalation
Absorption
=
100%
Special
FQPA
SF
=
1X
Residential
MOE
=
1000
Occupational
MOE
=
100
Same
as
above
for
chronic
dietary
exposures.

3.4
Endocrine
Disruption
EPA
is
required
under
the
Federal
Food,
Drug,
and
Cosmetic
Act
(
FFDCA,)
as
amended
by
the
Food
Quality
Protection
Act
(
FQPA),
to
develop
a
screening
program
to
determine
whether
certain
substances
(
including
all
pesticide
active
and
other
ingredients)
"
may
have
an
effect
in
humans
that
is
similar
to
an
effect
produced
by
a
naturally
occurring
estrogen,
or
other
such
endocrine
effects
as
the
Administrator
may
designate."
Following
the
recommendations
of
its
Endocrine
Disruptor
Screening
and
Testing
Advisory
Committee
(
EDSTAC),
EPA
determined
that
there
was
scientific
bases
for
including,
as
part
of
the
program,
the
androgen
and
thyroid
17
hormone
systems,
in
addition
to
the
estrogen
hormone
system.
EPA
also
adopted
EDSTAC's
recommendation
that
the
Program
include
evaluations
of
potential
effects
in
wildlife.
For
pesticide
chemicals,
EPA
will
use
FIFRA
and,
to
the
extent
that
effects
in
wildlife
may
help
determine
whether
a
substance
may
have
an
effect
in
humans,
FFDCA
authority
to
require
the
wildlife
evaluations.
As
the
science
develops
and
resources
allow,
screening
of
additional
hormone
systems
may
be
added
to
the
Endocrine
Disruptor
Screening
Program
(
EDSP).

When
the
appropriate
screening
and/
or
testing
protocols
being
considered
under
the
Agency's
EDSP
have
been
developed,
ETU
may
be
subjected
to
additional
screening
and/
or
testing
to
better
characterize
effects
related
to
endocrine
disruption.

4.0
Exposure
Assessment
and
Characterization
4.1
Summary
of
Registered
Uses
Ethylene
thiourea
(
ETU)
is
a
degradate
and
metabolite
of
the
ethylenebis
dithiocarbamate
(
EBDC)
fungicides
mancozeb,
maneb,
and
metiram.
The
EBDC
fungicides
are
used
on
numerous
agricultural
crops,
including
vegetables,
fruit
and
nut
trees,
field
and
forage
crops,
and
grapes;
for
seed
treatment;
on
turf,
including
golf
courses,
and
sod
farms;
on
ornamental
trees,
shrubbery,
perennials
and
annuals.
The
EBDCs
are
broad
spectrum
contact
fungicides
used
to
prevent
a
variety
of
fungal
diseases,
including
downy
mildews,
anthracnose,
rusts,
leaf
spots,
blights,
crown
rot,
molds,
cankers,
seed
rot
and
seedling
damping
off.
EBDC
end­
use
products
are
available
as
wettable
powder
(
WP),
dry
flowable
(
DF),
dust
(
D),
emulsifiable
concentrate
(
EC),
and
ready­
touse
formulations.

Mancozeb
and
maneb
have
the
most
food
uses,
while
metiram
food
uses
are
limited
to
apples
and
potatoes.
In
terms
of
annual
production
and
uses,
mancozeb
is
the
most
significant,
with
over
6
million
pounds
of
total
domestic
usage;
crops
with
the
largest
market
in
terms
of
pounds
active
ingredient
(
ai)
are
potatoes,
fresh
tomatoes
and
apples.
Maneb
domestic
usage
is
estimated
to
be
over
2
million
pounds
ai
annually;
crops
with
the
largest
markets
in
pounds
ai
are
potatoes,
peppers
(
bell
and
nonbell),
and
lettuce.
Metiram
domestic
usage
is
estimated
at
over
600,000
pounds
annually,
with
two­
thirds
of
the
pounds
ai
applied
to
apples,
and
one­
third
of
the
pounds
ai
applied
to
potatoes.
A
listing
of
the
label
application
rates
for
each
EBDC
is
given
in
Table
4.1.
Some
of
the
crops
have
more
than
one
EBDC
registered
for
use;
however,
the
total
amount
of
EBDCs
used
on
each
crop
is
restricted
by
the
following
label
statement:

"
If
more
than
one
product
containing
an
EBDC­
active
ingredient
(
maneb,
mancozeb,
or
metiram)
is
used
on
a
crop
during
the
same
growing
season,
the
total
poundage
of
all
such
EBDC
products
used
must
not
exceed
any
one
of
the
specified
individual
EBDC
product
maximum
seasonal
poundage
of
active
ingredient
allowed
per
acre."

The
maximum
season
rate
for
all
of
EBDCs
used
is
the
same
for
most
of
the
crops
regardless
of
which
EBDC
is
used.
In
the
case
of
cucumbers,
melons
and
squash,
however,
the
maximum
rate
per
season
depends
upon
which
EBDC
is
used.
The
Quantitative
Usage
Analyses
(
QUA)
(
F.
18
Hernandez,
12/
2/
02)
indicate
that
most
EBDC
usage
as
a
foliar
application
occurs
on
vegetables,
grapes,
pome
fruits,
tree
nuts
and
potatoes.
Very
little
usage
(
i.
e.
less
than
1%
crop
treated)
occurs
as
a
foliar
application
on
the
other
registered
uses
such
cereal
grains,
field
corn,
cotton
and
peanuts.
The
EBDCs
are
also
used
as
seed
treatments
for
vegetables,
cereal
grains,
corn,
cotton
and
peanuts.
In
response
to
comments
in
the
Phase
3
Public
Participation
Process
for
the
EBDC
REDs,
BEAD
has
provided
updated
usage
information
in
as
Screening
Level
Usage
Analysis
(
SLUA)
(
J.
Carter,
3/
31/
05).
Percent
Crop
Treated
(
PCT)
values
from
both
the
QUA
and
SLUA
were
used
in
this
assessment.
In
general
the
PCT
values
are
similar
from
both
analyses.
The
newer
PCT
values
were
used;
if
a
commodity
was
not
listed
in
the
SLUA,
but
was
included
in
the
QUA,
then
the
value
in
the
QUA
was
used.
Commodities
that
are
not
included
in
either
assessment
are
assumed
to
be
100%
crop
treated.
Both
the
SLUA
and
QUA
are
included
in
Appendix
1.

Table
4.1
­
Label
Application
Rates
for
EBDCs
Crop
Group
Crop(
s)
EBDC
Used
MZ
=
Mancozeb
MN
=
Maneb
MT
=
Metiram
Maximum
Label
Application
Rates
(
lb
ai/
acre)

Per
Application
Per
Season
Field
Crops
Barley,
Oats,
Rye,
Triticale,
Wheat
MZ
1.6
4.8
Field
Crops
Beans,
Dry
MN
1.6
9.6
Field
Crops
Corn:
hybrid
seedcorn
MZ,
MN
1.2
12
Field
Crops
Corn:
field
MZ
1.2
12
Field
Crops
Cotton
MZ
1.6
6.4
Field
Crops
Peanuts
MZ
1.6
12.8
Field
Crops
Sugar
Beets
MZ,
MN
1.6
11.2
Fruits
Bananas
MZ,
MN
2.4
24
Fruits
Cranberries
MZ,
MN
4.8
14.4
Fruits
Figs,
Kodota
MN
2.4
2.4
Fruits
Grapes
­
West
MZ,
MN
2
6
Fruits
Grapes­
East
MZ,
MN
3.2
19.2
Fruits
Papayas
MZ,
MN
2
28
Fruits
Plantains
MZ
2.4
24
Miscellaneous
Christmas
Trees,
Douglas
Fir
MZ
3.2
NA
Non­
Food
tobacco
fields
MZ
1.5
6
Non­
Food
tobacco
seedlings
MZ
2
None
Nut
Crops
Almonds
MN
6.4
25.6
Ornamentals
Ornamentals,
Pachysandra
MZ
13
­
14
NA
Ornamentals
Ornamentals,
Variety
MZ,
MN
1.2
­
1.6
NA
Pome
Fruits
Apples
MZ,
MN,
MT
2.4
or
4.8
16.8
or
19.2
Pome
Fruits
Pears,
Crabapples,
Quince
MZ
2.4
or
4.8
16.8
or
19.2
Turf
Sod
Farm
MZ,
MN
16.3
­
19
NA
Turf
Golf
Course,
Athletic
Fields
MZ
16.3
­
19
NA
Vegetables
Asparagus
MZ
1.6
6.4
Vegetables
Brassica
MN
1.6
9.6
Vegetables
Corn:
sweet/
pop/
seed:
East
of
Miss.
MZ,
MN
1.2
18
Vegetables
Corn:
sweet/
pop/
seed:
West
of
Miss.
MZ,
MN
1.2
6
Vegetables
Cucumbers
MZ,
MN
MZ
=
2.4
MN
=
1.6
MZ
=
19.2
MN
=
12.8
Vegetables
Fennel
MZ
1.6
12.8
Table
4.1
­
Label
Application
Rates
for
EBDCs
Crop
Group
Crop(
s)
EBDC
Used
MZ
=
Mancozeb
MN
=
Maneb
MT
=
Metiram
Maximum
Label
Application
Rates
(
lb
ai/
acre)

Per
Application
Per
Season
19
Vegetables
Gourds:
Edible
MZ
2.4
19.2
Vegetables
Lettuce
MN
1.6
6.4
(
CA),
9.6
(
US)

Vegetables
Melons
MZ,
MN
MZ
=
2.4
MN
=
1.6
MZ
=
19.2
MN
=
12.8
Vegetables
Onions:
Dry
Bulb,
Garlic
MZ,
MN
2.4
24
Vegetables
Onions:
Green
MN
2.4
11.2
Vegetables
Peppers
MN
1.6
(
w),
2.4
(
e)
9.6
(
w),
14.4
(
e)

Vegetables
Potatoes
MZ,
MN,
MT
1.6
11.2
Vegetables
Pumpkins
MN
1.6
12.8
Vegetables
Shallots
MZ,
MN
2.4
24
Vegetables
Squash
(
winter)
Squash
(
summer)
MN
MZ,
MN
MZ
=
2.4
MN
=
1.6
MZ
=
19.2
MN
=
12.8
Vegetables
Tomatoes
MZ,
MN
2.4
(
w),
1.6
(
e)
6.4
(
w),
16.8
(
e)

Vegetables
Watermelons
MZ,
MN
2.4
19.2
Note
­
Crops
in
bold
have
different
rates
depending
upon
which
EBDC
is
used
4.2
Food
Dietary
Exposure/
Risk
Pathway
In
association
with
the
RED
for
each
EBDC,
separate
dietary
exposure
assessments
were
conducted.
In
each
of
these
assessments,
human
dietary
exposure
and
health
risk
associated
with
the
active
ingredient
were
estimated.
Also
addressed
in
each
assessment
are
the
dietary
exposure
and
risk
resulting
from
consumption
of
ETU
residues
derived
from
each
EBDC
individually.
These
documents
are
listed
below:

°
Mancozeb:
Acute
Probabilistic,
Chronic,
and
Cancer
Dietary
Exposure
Assessments
for
the
Reregistration
Eligibility
Decision;
DP
Barcode:
D305814;
June
2005;
F.
Fort
and
T.
Jimerson
°
Maneb
and
Ethylenethiourea:
Revised
Acute/
Probabilistic,
Chronic,
and
Cancer
Dietary
Exposure
Assessments
for
the
Reregistration
Eligibility
Decision;
DP
Barcode:
D295410;
June
2005;
F.
Fort.
°
Metiram:
Acute,
Chronic,
and
Cancer
Dietary
Exposure
Assessments
for
the
Reregistration
Eligibility
Decision;
DP
Barcode:
D305909:
10/
13/
04;
F.
Fort.

In
the
dietary
assessment
the
ETU
food
residues
from
each
of
the
EBDCs
are
aggregated.
In
some
cases
these
aggregations
occur
because
the
different
EBDCs
are
used
on
different
crops
which
are
combined
together
to
make
up
the
daily
diet.
In
other
cases
different
EBDCs
are
used
on
the
same
crop
and
the
aggregation
consists
of
adding
some
combination
of
the
ETU
residues
from
each
EBDC.
This
process
is
described
further
in
the
following
sections.

Crops
treated
with
EBDCs
may
contain
both
EBDC
and
ETU
residues;
in
addition,
cooking
and/
or
processing
may
result
in
conversion
of
EBDC
residues
to
ETU,
or
in
concentration
or
20
reduction
of
existing
ETU
residues.
Therefore,
both
EBDC
and
ETU
residues
may
be
consumed
in
the
diet.

Residue
Data
used
for
Acute,
Chronic,
and/
or
Cancer
Assessments
HED
typically
uses
two
types
of
monitoring
data
in
its
probabilistic
acute
dietary
exposure
assessments.
For
commodities
considered
to
be
partially
blended,
such
as
juices
or
small
fruits,
composite
samples
consisting
of
2
to
5
lbs
are
expected
to
have
similar
residues
to
smaller
quantities
that
would
be
consumed
as
a
single
serving.
However,
for
non­
blended
commodities,
such
as
apples
or
bananas,
residues
in
a
2
to
5
lb
composite
are
not
considered
representative
of
the
highest
residue
that
might
be
present
in
a
single
fruit
(
single
unit).
Use
of
composite
sample
residues
for
non­
blended
commodities
in
an
acute
probabilistic
analysis
would
underestimate
potential
dietary
exposure
and
risk.
If
available,
single
unit
(
often
referred
to
as
single­
serving)
residue
data
are
used
in
acute
assessments.
In
the
absence
of
single
unit
monitoring
data
(
e.
g.,
from
USDA/
PDP
or
registrants),
and
in
order
to
conduct
a
more
refined
dietary
exposure
assessment,
HED
typically
uses
a
statistical
procedure
known
as
'
decompositing'
to
better
estimate
the
maximum
potential
residue
levels
(
e.
g.,
theoretical
single
unit
residues)
from
composite
monitoring
samples.

When
possible,
market
basket
survey
(
MBS)
data,
generated
by
the
ETU
Task
Force,
were
used
to
calculate
anticipated
residues.
Although
the
EBDC/
ETU
MBS
data
were
collected
in
1989/
1990,
the
Agency
has
determined
that
these
data
are
essentially
as
representative
of
EBDC
fungicide
use
today
as
they
were
13
years
ago;
extensive
justification
of
this,
particularly
in
terms
of
minimal
changes
in
PCT
and
application
rates
over
the
years,
has
been
provided
by
C.
Swartz
(
7/
11/
03;
D290137,
D290139,
and
D290140).
MBS
data
are
available
on
the
following
foods:
green
beans
(
raw,
frozen,
canned,
and
baby
food),
dry
beans
(
dry
and
canned),
broccoli
(
raw
and
frozen),
celery,
sweet
corn
(
raw,
frozen,
canned),
cucumbers,
lettuce,
meat,
milk,
onion
(
dry
bulb),
potato
(
raw,
frozen),
and
tomato
(
raw,
juice,
ketchup,
paste,
puree).

In
the
EBDC/
ETU
Market
Basket
Survey,
samples
were
purchased
at
consumer
retail
outlets.
Shoppers
were
instructed
to
select
blemish
free
commodities
in
amounts
similar
to
those
purchased
by
typical
consumers.
The
shoppers
were
also
advised
to
purchase
the
commodities
in
bags
wherever
possible,
with
the
assumption
that
bagged
commodities
were
more
likely
to
come
from
the
same
field.
For
example,
the
protocol
directed
shoppers
to
select
eight
cucumbers
for
each
sample.
The
samples
were
composited
and
a
subsample
was
taken
for
the
analyses.

The
EBDC/
ETU
MBS
data
for
non­
blended
commodities
were
not
decomposited
for
the
EBDC
acute
dietary
exposure
assessments.
Although
this
may
underestimate
acute
dietary
exposure
to
some
extent,
HED
decided
to
use
the
composite
data
directly
when
considering
that
(
1)
the
samples
taken
for
the
MBS
were
of
a
smaller
size
than
is
done
for
most
other
monitoring
studies,
and
the
shoppers
were
instructed
to
take
samples
from
the
same
lot,
both
of
which
should
lead
to
a
more
homogeneous
residue
distribution
within
the
sample;
(
2)
shoppers
were
instructed
to
choose
blemish­
free
fruit
or
vegetables
(
for
fresh
commodities),
increasing
the
likelihood
that
treated
commodities
were
selected;
(
3)
decompositing
samples
for
metabolite
ETU
residues
would
not
be
appropriate,
since
the
likelihood
of
finding
ETU
does
not
have
a
consistent
relationship
with
detection
of
EBDC
residues;
and
(
4)
acute
risks
are
not
particularly
of
concern
21
for
EBDCs;
rather,
the
cancer
risks
are
of
primary
concern,
and
use
of
composite
residue
values
is
appropriate
for
cancer
exposure
and
risk
assessment.
Although
acute
dietary
exposure
and
risk
from
monitored
commodities
may
be
slightly
underestimated
because
the
MBS
samples
were
not
decomposited,
the
risk
from
other
(
non­
monitored)
commodities
is
likely
to
be
greatly
overestimated
because
field
trial
data
were
used,
and
because,
in
some
instances,
an
assumption
of
100
PCT
was
used.

Refer
to
the
individual
EBDC
anticipated
residue
and/
or
dietary
assessment
for
detailed
information
on
the
derivation
of
the
residue
inputs.

Acute
Anticipated
Residues
For
the
probabilistic
acute
dietary
exposure
analysis,
the
entire
distributions
of
residue
data
from
field
trials
or
monitoring
data
were
used
to
generate
residue
distribution
files
(
RDFs)
for
commodities
that
are
considered
to
be
not
blended
or
partially
blended.
For
commodities
considered
to
be
blended
in
this
analysis;
the
average
residues
incorporating
the
likely
maximum
estimated
PCT
was
used
as
a
point
estimate.

In
acute
analyses
(
except
blended
commodities)
the
adjustment
for
PCT
was
incorporated
in
the
residue
distribution
files
(
RDFs)
via
addition
of
zero
residue
values
corresponding
to
the
%
of
crop
not
treated.
For
blended/
not
further
processed
commodities
where
monitoring
data
were
available,
the
entire
distribution
of
monitoring
data
with
no
further
adjustment
for
PCT
were
used.
For
blended/
processed
commodities
where
monitoring
data
were
available
and
for
all
blended
commodities
where
field
trial
data
were
used,
PCT
was
incorporated
into
a
point
estimate.

Chronic
Anticipated
Residues
Chronic
anticipated
residues
were
also
calculated
from
field
trial
or
monitoring
data
for
ETU.
Averages
of
the
field
trial
and
MBS
residues
were
used.
In
determining
the
average
residue
when
two
or
more
EBDCs
are
used
on
a
crop,
the
following
equation
was
used.

(
ETU
from
Mancozeb
Residue
x
Mancozeb
PCT/
100)
+
(
ETU
from
Maneb
residue
x
Maneb
PCT/
100)
+
(
ETU
from
Metiram
residue
x
Metiram
PCT/
100)
=
Chronic
AR
for
ETU
If
the
sum
of
the
PCT
values
for
all
three
EBDCs
exceeded
100%
then
the
PCT
values
were
adjusted
so
that
the
sum
equaled
100%.

4.3
Water
Exposure/
Risk
Pathway
The
OPP
Environmental
Fate
and
Effects
Division
(
EFED)
prepared
a
drinking
water
exposure
assessment
for
ETU,
which
is
applicable
for
mancozeb,
as
well
as
the
other
EBDCs.
The
EBDC
fungicides,
Metiram,
Maneb
and
Mancozeb
are
very
short
lived
in
soil
and
in
water
and
would
not
22
themselves
be
expected
to
remain
in
surface
water
long
enough
to
reach
a
location
that
would
supply
water
for
human
consumption
whether
from
surface
or
groundwater.
However,
ETU
is
highly
water
soluble,
and
may
reach
both
surface
and
ground
water
under
some
conditions.
The
drinking
water
exposure
assessment
for
mancozeb,
maneb
and
metiram
addresses
concentrations
of
ETU
only.

The
ETU
estimated
drinking
water
concentrations
(
EDWCs)
were
generated
using
data
from
monitoring
and
modeling.
See
sections
4.3.2
and
4.3.3
below,
for
more
details.

ETU
Surface
Water
EDWCs
(
from
PRZM­
EXAMS
modeling
and
from
monitoring
data):
acute
(
peak)
surface
water
=
range
of
0.1
(
monitoring)
to
25.2
ppb
(
modeling)
chronic/
cancer
surface
water
=
0.1
ppb
(
from
monitoring)

ETU
Ground
Water
EDWC
(
from
a
Targeted
Monitoring
Study
in
FL):
acute/
chronic/
cancer
ground
water
=
0.21
ppb
(
from
monitoring)

4.3.1
Environmental
Fate
The
EBDC
metabolite/
degradate
ETU
has
an
aerobic
soil
half­
life
of
about
3
days;
in
the
absence
of
data,
the
aquatic
aerobic
metabolism
half­
life
was
assumed
to
be
about
6
days,
or
double
the
soil
half
life.
The
measured
anaerobic
aquatic
metabolism
half­
life,
however,
is
substantially
longer
(
149
days)
possibly
leading
to
the
periodic
detections
in
ground
water.
ETU
is
highly
soluble
in
water
(
20,000
ppm);
highly
vulnerable
to
indirect
photolysis
(
half­
life=
1
day),
and
moderately
mobile
(
288
L/
kg).
It
also
has
a
relatively
high
vapor
pressure
but
high
solubility
reduces
the
possibility
of
losses
from
surface
water
due
to
volatilization.

4.3.2
Surface
Water
Water
Monitoring:
The
EBDC/
ETU
Task
Force
conducted
a
national
surface
water
monitoring
survey
from
2001­
2003.
A
total
of
22
sites
were
chosen
to
represent
vulnerable
and
high
EBDCuse
sites.
Surface
water
sites
were
sampled
twice
monthly
for
three
months
during
each
application
season
and
quarterly
for
the
three
remaining
quarters
of
each
year
for
a
period
of
2
years.
There
were
no
detections
of
ETU
in
surface
water
during
this
period.
The
limit
of
quantitation
for
the
study
was
0.1
ppb.

The
Agency
has
been
unable
to
locate
any
other
surface
water
monitoring
data
for
the
EBDC
fungicides
or
for
ETU.
The
EBDCs
and
ETU
were
not
included
in
the
US
Geological
Survey
(
USGS)
National
Water
Quality
Assessment
(
NAWQA)
sampling
program
because
EBDC/
ETU
test
methods
were
incompatible
with
NAWQA
test
methods.
The
USGS
is
currently
planning
to
begin
method
development
and
limited
EBDC/
ETU
monitoring
in
late
2004.
23
Water
Modeling:
The
ETU
surface
water
estimates
were
calculated
using
the
linked
USEPA
PRZM
(
Pesticide
Root
Zone
Model)
and
EXAMS
(
Exposure
Analysis
Model
System)
simulation
models.
This
type
of
modeling
provide
high­
end
estimates
for
surface
water
pesticide
concentrations.
Calculation
includes
pesticide­
specific
properties,
multiple
years
of
actual
weather
variations,
and
crop­
specific
information.
In
addition
to
runoff
from
the
field,
the
model
takes
into
account
surface
water
residues
resulting
from
spray
drift
(
aerial
or
ground).
Conservative
assumptions
included
the
use
of
a
vulnerable
drinking
water
reservoir
surrounded
by
a
runoff­
prone
watershed,
maximum
use
rate,
lowest
application
intervals,
and
no
buffer
zone.
Modeling
was
done
for
22
crop
scenarios.

The
highest
one­
in­
ten
year
acute
surface
water
EDWC
was
25.2
ppb
and
the
lowest
value
was
4.5
ppb.
These
values
were
calculated
using
the
national
percent
cropped
area
(
PCA)
value
of
0.87.
It
the
maximum
regional
PCA
value
(
0.56
California
PCA)
is
used,
then
the
highest
acute
surface
water
EDWC
was
13.9
ppb
and
the
lowest
is
1.4
ppb.

The
highest
chronic
concentration
value
was
1.9
ppb
and
the
lowest
value
was
0.2
ppb.
This
was
calculated
using
the
national
maximum
PCA.

Acute
Surface
Water
EDWCs:
The
ETU
surface
water
estimated
drinking
water
concentrations
(
EDWCs)
were
generated
using
a
combined
monitoring/
modeling
approach.
The
targeted
ETU
monitoring
found
no
surface
water
concentrations
above
the
detection
limit
of
0.1
ppb.
Because
samples
were
taken
every
14
days
during
the
application
season
and
acute
values
may
have
been
missed,
a
range
of
acute
surface
EDWCs
was
established
with
a
lower
limit
based
on
monitoring
and
an
upper
limit
based
on
PRZM/
EXAMS
modeling.

The
range
of
acute
EDWCs
was
0.1
ppb
(
monitoring)
and
the
upper
limit
was
25.2
ppb.
The
values
were
adjusted
by
the
national
maximum
default
PCA
value
of
0.87.

Chronic
Surface
Water
EDWC:
The
chronic
EDWC
is
0.1
ppb
from
the
targeted
ETU
monitoring
program
mentioned
above.
No
surface
water
concentrations
were
found
above
the
detection
limit
of
0.1
ppb
and
the
Agency
believes
that
monitoring
demonstrates
that
long­
term
average
chronic
values
would
not
exceed
the
detection
limit.

4.3.3
Ground
Water
Water
Monitoring:
A
monitoring
program
of
community
ground
water
systems
was
conducted
by
the
EBDC
Task
Force
from
2001­
2003.
Untreated
and
associated
treated
ground
water
were
sampled
for
a
period
of
two
years
in
84
sites
chosen
to
represent
high
EBDC­
use
sites.
ETU
was
detected
above
the
detection
limit
intermittently
in
untreated
water
from
two
ground
water
sites.
The
highest
concentration
was
0.21
ppb
in
untreated
water
in
Florida.
There
were
no
detections
in
treated
water
in
any
of
the
84
community
water
sites;
including
those
two
sites
where
ETU
was
detected
in
the
untreated
water.
24
A
monitoring
program
of
private
wells
was
conducted
by
the
EBDC
Task
Force
from
2001­
2003.
Raw
ground
water
was
sampled
monthly
for
a
period
of
two
years
in
125
sites
chosen
to
represent
high
EBDC­
use
sites.
ETU
was
detected
in
the
range
of
0.10
to
0.25
ppb
continuously
at
2
sites
in
Florida
and
intermittently
at
six
sites:
three
in
Florida
and
one
each
in
New
York,
Illinois
and
Maine
(
Figure
3).
The
highest
detected
ETU
concentration
measured
for
a
private
well
near
an
EBDC
treated
field
was
0.57
ppb
in
an
apple
growing
region
of
New
York.
No
detection
of
ETU
was
observed
in
all
the
other
117
sites.
Such
higher
groundwater
concentration
values,
found
in
private
areas
in
rural
areas,
are
very
rare
and
are
unlikely
to
represent
ground
water
ETU
concentrations
expected
in
drinking
water
relevant
for
use
in
a
national
assessment.

In
25
years
of
monitoring
in
California,
there
has
been
only
one
ETU
detection
(
0.75
ppb).
Additionally,
ground
water
monitoring
in
Holland,
resulted
in
only
8
positive
samples
with
a
maximum
concentration
of
1.5
ppb.

Water
Modeling:
The
ETU
EDWCs
in
ground
water,
derived
from
the
industry's
targeted
ground
water
monitoring
study,
were
evaluated
by
comparing
them
to
concentrations
predicted
by
the
SCI­
GROW
model.
This
is
a
screening
model
used
to
estimate
pesticide
concentrations
in
vulnerable
ground
water.
The
SCI­
GROW
estimate
is
based
on
environmental
fate
properties
of
the
pesticide,
maximum
application
rate,
and
existing
data
from
small­
scale
prospective
ground
water
monitoring
studies
at
sites
with
sandy
soils
and
shallow
ground
water
(
i.
e.,
exceptionally
vulnerable
ground
water).
Pesticide
concentrations
estimated
by
SCI­
GROW
represent
conservative
or
high­
end
exposure
values
and
in
most
cases,
use
areas
will
have
groundwater
that
is
less
vulnerable
to
contamination
than
the
areas
used
to
derive
the
SCIGROW
estimate.
The
SCI­
GROW
modeling
indicates
that
the
upper
level
ETU
concentrations
from
the
targeted
monitoring
study
are
unlikely
to
be
exceeded
even
under
the
most
vulnerable
conditions.

Ground
Water
EDWCs
(
acute
and
chronic):
For
ETU,
the
EDWC
value
for
both
acute
and
chronic
exposure
is
0.21
ppb.
This
value
is
from
monitoring
untreated
water
in
Florida.

4.4
Acute,
Chronic,
and
Cancer
Dietary
Risk
Analysis
4.4.1
Usage
Data
BEAD
provided
information
(
F.
Hernandez,
12/
2/
02,)
on
the
percent
crop
treated
(%
CT).
For
the
chronic
analysis,
the
weighted
average
%
CT
was
used.
PCT
values
from
both
the
QUA
and
SLUA
were
used
in
this
assessment.
In
general
the
PCT
values
are
similar
from
both
analyses.
The
newer
PCT
values
were
used;
if
a
commodity
was
not
listed
in
the
SLUA,
but
was
included
in
the
QUA,
then
the
value
in
the
QUA
was
used.
Commodities
that
are
not
included
in
either
assessment
are
assumed
to
be
100%
crop
treated.

In
acute
analyses
(
except
blended
commodities)
the
adjustment
for
%
CT
is
incorporated
in
the
residue
distribution
files
(
RDFs)
via
addition
of
zero
residue
values
corresponding
to
the
%
of
crop
not
treated.
For
blended/
not
further
processed
commodities
where
monitoring
data
are
available,
the
entire
distribution
of
monitoring
data
with
no
further
adjustment
for
%
CT
were
25
used.
For
blended/
processed
commodities
where
monitoring
data
are
available
and
for
all
blended
commodities
where
field
trial
data
were
used,
%
CT
is
incorporated
into
a
point
estimate.

Additional
information
can
be
found
in
the
document,
Ethylene
bisdithiocarbamates
[
Mancozeb,
Maneb,
and
Metiram].
Summary
of
Percent
Crop
Treated
(%
CT),
and
Justification
for
Use
of
the
1990
EBDC
Market
Basket
Survey
in
Dietary
Exposure
Assessments
for
Reregistration.
Mancozeb
DB
Barcode
No.
D290139;
Maneb
DP
Barcode
No.
D290140;
Metiram
DB
Barcode
No.
D290137.[
9/
4/
03],
C.
Swartz.

4.4.2
Processing
Factors
Processing
factors
were
obtained
from
processing
studies
submitted
by
the
registrant
and
were
compiled
in
a
memo
entitled
"
Reregistration
of
Mancozeb,
Maneb,
and
Metiram:
Processing
and
Cooking
Factors
to
be
Used
in
the
Dietary
Risk
Assessment",
(
C.
Olinger,
DP
Barcodes
D289569,
D289570,
and
D289571,
11/
05/
03).
These
factors
include
cooking,
peeling,
washing
and
processing
factors.

4.4.3
DEEM­
FCID
 
Program
and
Consumption
Information
Dietary
exposure
assessments
were
conducted
using
the
Dietary
Exposure
Evaluation
Model
software
with
the
Food
Commodity
Intake
Database
(
DEEM­
FCID
 
,
Version
1.3),
which
incorporates
consumption
data
from
USDA's
Continuing
Surveys
of
Food
Intakes
by
Individuals
(
CSFII),
1994­
1996
and
1998.
The
1994­
96,
98
data
are
based
on
the
reported
consumption
of
more
than
20,000
individuals
over
two
non­
consecutive
survey
days.
Foods
"
as
consumed"
(
e.
g.,
apple
pie)
are
linked
to
EPA­
defined
food
commodities
(
e.
g.
apples,
peeled
fruit
­
cooked;
fresh
or
N/
S;
baked;
or
wheat
flour
­
cooked;
fresh
or
N/
S,
baked)
using
publicly
available
recipe
translation
files
developed
jointly
by
USDA/
ARS
and
EPA.
Consumption
data
are
averaged
for
the
entire
U.
S.
population
and
within
population
subgroups
for
chronic
exposure
assessment,
but
are
retained
as
individual
consumption
events
for
acute
exposure
assessment.

For
chronic
exposure
and
risk
assessment,
an
estimate
of
the
residue
level
in
each
food
or
foodform
(
e.
g.,
orange
or
orange
juice)
on
the
food
commodity
residue
list
is
multiplied
by
the
average
daily
consumption
estimate
for
that
food/
food
form.
The
resulting
residue
consumption
estimate
for
each
food/
food
form
is
summed
with
the
residue
consumption
estimates
for
all
other
food/
food
forms
on
the
commodity
residue
list
to
arrive
at
the
total
average
estimated
exposure.
Exposure
is
expressed
in
mg/
kg
body
weight/
day
and
as
a
percent
of
the
cPAD.
This
procedure
is
performed
for
each
population
subgroup.

For
acute
exposure
assessments,
individual
one­
day
food
consumption
data
are
used
on
an
individual­
by­
individual
basis.
The
reported
consumption
amounts
of
each
food
item
can
be
multiplied
by
a
residue
point
estimate
and
summed
to
obtain
a
total
daily
pesticide
exposure
for
a
deterministic
(
Tier
1
or
Tier
2)
exposure
assessment,
or
"
matched"
in
multiple
random
pairings
26
with
residue
values
and
then
summed
in
a
probabilistic
(
Tier
3/
4)
assessment.
The
resulting
distribution
of
exposures
is
expressed
as
a
percentage
of
the
aPAD
on
both
a
user
(
i.
e.,
those
who
reported
eating
relevant
commodities/
food
forms)
and
a
per­
capita
(
i.
e.,
those
who
reported
eating
the
relevant
commodities
as
well
as
those
who
did
not)
basis.
In
accordance
with
HED
policy,
per
capita
exposure
and
risk
are
reported
for
all
tiers
of
analysis.
However,
for
tiers
1
and
2,
significant
differences
in
user
vs.
per
capita
exposure
and
risk
are
identified
and
noted
in
the
risk
assessment.

4.4.4
Acute
Dietary
Risk
Analysis
The
acute
dietary
assessment
was
conducted
only
for
females
13­
49
because
this
was
the
only
population
subgroup
of
concern
for
acute
effects.
The
NOAEL
of
5
mg/
kg/
day
for
development
defects
was
used
to
establish
the
aPAD
of
0.005
mg/
kg/
day
(
5.0
µ
g/
kg/
day)
by
dividing
it
by
the
uncertainty
factor
of
1000.
The
exposures
were
obtained
from
DEEM­
FCID.
The
percent
aPAD
does
not
exceed
100%
highest
level
of
exposure
(
99.9th
percentile)
which
means
that
the
risks
are
not
of
concern.
The
results
for
food
alone
are
included
in
Table
4.2a,
and
food
and
water
in
Table
4.2b.

Table
4.2a
­
Results
of
Acute
Dietary
Exposure
Analysis
(
Food
Alone)

Population
Subgroup
aPAD
(
mg/
kg/
day)
95th
Percentile
99th
Percentile
99.9th
Percentile
Exposure
(
mg/
kg/
day)
%
aPAD
Exposure
(
mg/
kg/
day)
%
aPAD
Exposure
(
mg/
kg/
day)
%
aPAD
Females
13­
49
years
old
0.005
0.000098
2.0
0.000551
11
0.002725
55
Table
4.2b
­
Results
of
Acute
Dietary
Exposure
Analysis
(
Food
and
Water)*

Population
Subgroup
aPAD
(
mg/
kg/
day)
95th
Percentile
99th
Percentile
99.9th
Percentile
Exposure
(
mg/
kg/
day)
%
aPAD
Exposure
(
mg/
kg/
day)
%
aPAD
Exposure
(
mg/
kg/
day)
%
aPAD
Females
13­
49
years
old
0.005
0.001304
26
0.002148
43
0.004331
87
*
EDWC
=
25.2
ppb
4.4.5
Chronic
Dietary
Risk
Analysis
The
chronic
dietary
assessment
was
conducted
for
all
populations
because
the
endpoint
of
concern
is
applicable
to
all
populations.
The
NOAEL
of
0.18
mg/
kg/
day
for
thyroid
effects
observed
during
the
chronic
toxicity
study
was
used
to
establish
the
cPAD
of
0.0002
mg/
kg/
day
by
dividing
it
by
the
uncertainty
factor
of
1000.
The
exposures
were
obtained
from
DEEMFCID
The
percent
aPAD
does
not
exceed
100%
for
the
most
sensitive
population
which
means
that
the
risks
are
not
of
concern.
The
results
for
food
alone
are
included
in
Table
4.3a,
and
for
food
plus
water
are
included
in
Table
4.3b.
27
Table
4.3a.
Results
of
ETU
Aggregate
Chronic
Dietary
Exposure
Analysis
(
Food
Alone)

Population
Subgroup
cPAD
(
mg/
kg/
day)
Exposure
(
mg/
kg/
day)
%
cPAD
General
U.
S.
Population
0.0002
0.000031
16
All
Infants
(<
1
year
old)
0.0002
0.0000061
31
Children
1­
2
years
old
0.0002
0.000108
54
Children
3­
5
years
old
0.0002
0.000072
36
Children
6­
12
years
old
0.0002
0.000033
16
Youth
13­
19
years
old
0.0002
0.000021
11
Adults
20­
49
years
old
0.0002
0.000025
12
Adults
50+
years
old
0.0002
0.000026
13
Females
13­
49
years
old
0.0002
0.000027
14
**
The
values
for
the
highest
exposed
population
for
each
type
of
risk
assessment
are
bolded.

Table
4.3b.
Results
of
Chronic
Dietary
Exposure
Analysis
for
Food
and
Drinking
Water
Population
Subgroup
cPAD
(
mg/
kg/
day)
Surface
Water
EDWC
(
0.1
ppb)
Groundwater
EDWC
(
0.21
ppb)

Exposure
(
mg/
kg/
day)
%
cPAD
Exposure
(
mg/
kg/
day)
%
cPAD
General
U.
S.
Population
0.0002
0.000033
17
0.000035
18
All
Infants
(<
1
year
old)
0.0002
0.000068
33
0.000076
38
Children
1­
2
years
old
0.0002
0.000111
56
0.000115
58
Children
3­
5
years
old
0.0002
0.000075
37
0.000078
39
Children
6­
12
years
old
0.0002
0.000035
17
0.000037
18
Youth
13­
19
years
old
0.0002
0.000023
12
0.000024
12
Adults
20­
49
years
old
0.0002
0.000027
13
0.000029
15
Females
13­
49
years
old
0.0002
0.000028
14
0.000030
15
Adults
50+
years
old
0.0002
0.000029
15
0.000031
16
4.4.6
Cancer
Dietary
Risk
Analysis
The
dietary
cancer
risk
was
calculated
for
the
general
U.
S.
population
and
presented
in
Table
4.4a
for
food
alone,
and
for
food
and
water
in
Table
4.4b.
The
estimated
exposure
of
the
general
U.
S.
28
population
to
ETU
is
0.000031
mg/
kg/
day.
Applying
the
Q
1
*
of
0.0601(
mg/
kg/
day)­
1
to
the
exposure
value
results
in
a
cancer
risk
estimate
of
1.86
x
10­
6.
Therefore,
estimated
cancer
risk
is
slightly
above
HED's
level
of
concern.
A
Commodity
Contribution
Analysis
conducted
showed
that
leaf
lettuce
and
apple
juice
were
the
major
contributors
to
the
risk
estimates.

Table
4.4a
Results
of
Cancer
Dietary
Exposure
Analysis
­
Food
Alone
Population
Subgroup
Exposure
(
mg/
kg/
day)
Estimated
Cancer
Risk
General
U.
S.
Population
0.000031
1.86
x
10­
6
Table
4.4b
Results
of
Cancer
Dietary
Exposure
Analysis
­
Food
and
Drinking
Water
Population
Subgroup
Exposure
(
mg/
kg/
day)
Estimated
Cancer
Risk
General
U.
S.
Population
(
Drinking
water
Source
­
Ground
Water)
0.000035
2.1
x
10­
6
General
U.
S.
Population
(
Drinking
water
Source
­
Surface
Water)
0.000033
2.0
x
10­
6
4.4.7
Dietary
Risk
Characterization
In
general,
the
assessments
were
highly
refined
since
the
residues
were
from
either
field
trial
or
MBS
data.
Almost
all
data
sets
were
adjusted
for
percent
of
crop
treated.
All
plant
and
livestock
commodity
data
sets
were
refined
by
the
application
of
one
or
more
of
the
relevant
washing,
peeling,
cooking,
processing,
and
in
vivo
factors
to
estimate
the
degree
of
degradation
of
the
EBDC
to
ETU
as
well
as
the
conversion
of
the
EBDC
into
ETU
via
physicochemical
or
metabolic
processes.
However,
there
are
several
uncertainties
associated
with
dietary
exposure
analyses.
These
tend
to
result
in
more
conservative
exposure
estimates
including
the
following:

°
Field
trial
data
are
conservative
as
they
represent
residues
at
harvest
as
opposed
to
residues
at
the
time
of
consumption.
Thus,
the
dissipation
of
residues
during
shipping
and
storage
are
not
reflected
in
these
data.

°
For
maneb,
the
adequacy
of
the
residue
data
to
support
tolerances
is
poor
for
apple,
grape,
seed­
treated
crops,
leaf
lettuce,
all
other
leafy
greens,
fig,
cranberry,
and
papaya.
This
is
based
on
extremely
limited
sampling
and/
or
lack
of
adherence
to
the
registered/
PD4
directed
use
patterns.
In
all
of
these
cases,
either
extrapolation
to
the
label
use
pattern
or
use
of
mancozeb
field
trial
data
were
necessary
to
estimate
maneb
and
ETU
dietary
exposure.
In
the
case
of
leaf
lettuce,
contribution
to
the
risk
are
moderate
to
high.
Higher
quality
data
would
provide
much
more
confidence
in
the
exposure
assessment
although
such
data
may
either
increase
or
decrease
dietary
exposure.

°
Use
of
100%
crop
treated
was
necessary
for
several
crops
such
as
Belgium
endive,
Brussels
sprouts,
cranberry
(
acute
only),
endive,
flax,
papaya,
safflower,
and
turnips
grown
only
for
tops.
In
the
cases
of
endives,
papaya,
and
turnip
tops,
accurate
estimates
of
PCT
would
29
help
refine
exposure
estimates
for
these
low
to
moderate
exposure
and
risk
contributors,
depending
on
the
assessment.

°
Although
studies
are
available
to
determine
the
loss
of
ETU
and
conversion
of
EBDC
to
ETU
upon
cooking
and
certain
processing
steps,
little
data
are
available
to
ascertain
the
degree
of
physical
ETU
removal
during
washing,
peeling,
etc.
As
a
result,
many
ETU
estimates
are
expected
to
be
somewhat
conservative
even
though
the
majority
of
ETU
residues
are
not
likely
to
be
on
the
surface
of
foods.

C
The
generation
of
market
basket
survey
data
to
be
used
in
dietary
exposure
assessments
to
replace
the
field
trial
data
used
for
numerous
crops
would
permit
major
refinements.
Single
unit
sampling
would
permit
further
refinement
although
it
was
deemed
that
decomposition
of
MBS
data
was
not
necessary
at
this
time.

C
Registrant­
generated
washing,
cooking,
and
processing
studies
are
available
and
the
CARC
determined
that
7.5%
of
the
consumed
EBDC
could
get
metabolized
to
ETU
in
vivo.
These
factors
were
applied
directly
to
the
field
trial
or
MBS
data
with
fairly
liberal
translation
between
commodities.
It
is
suspected
that
some
factors,
when
applied
to
certain
foods,
may
either
underestimate
or
overestimate
exposure.
Generally,
conversion
of
EBDC
to
ETU
due
to
heating
is
the
step
resulting
in
the
most
significant
conversion
of
EBDC
to
ETU.
The
overall
conclusion
considering
all
of
the
applied
factors
in
toto
is
that
net
exposure
will
not
be
underestimated.
In
the
case
of
meat,
there
are
cooking
data
to
estimate
losses
and
conversion
of
residues.

4.5
Residential
and
Recreational
Exposure/
Risk
Pathway
Currently
the
agricultural
and
horticultural
labels
have
statements
such
as
"
Not
for
Homeowner
Use"
and
"
Not
for
Use
on
Fruit
Trees
by
Homeowners"
that
prevent
homeowner
applications
of
EBDCs
to
turf
and
fruit
trees.
The
registrants
have
also
stated
that
they
will
amend
the
labels
to
eliminate
lawn
care
operator
applications
to
residential
turf.
Applications
will
thus
be
limited
to
sod
farms,
golf
courses
and
athletic
fields.
Currently
there
are
no
mancozeb
labels
in
OPPIN
that
are
intended
for
the
home
garden
market.
There
are
labels
that
allow
application
of
maneb
in
home
gardens;
however,
these
labels
are
very
old
and
the
maneb
registrant
has
indicated
that
residential
uses
of
maneb
will
not
be
supported.

Based
on
the
use
patterns,
there
is
a
potential
for
adult
exposure
to
ETU
residues
while
playing
golf
on
turf
treated
with
EBDCs
as
well
as
athletes
playing
on
treated
fields.
Children
may
be
exposed
to
ETU
residues
while
playing
on
transplanted
turf.

The
target
Margin
of
Exposure
(
MOE)
for
residential
risk
is
1000,
based
on
the
combined
uncertainty
factors
(
UFs)
associated
with
endpoint
selection
for
dermal,
inhalation
and
nondietary
risk
assessments.
30
Cancer
risks
were
calculated
for
adult
golfers
and
athletes
because
the
mancozeb
is
routinely
used
on
golf
courses
and
athletic
fields.
Cancer
risks
were
not
calculated
for
transplanted
turf
exposures
because
turf
transplantation
is
an
infrequent
event
in
the
life
of
a
typical
homeowner.

4.5.1
Home
Garden
Uses
Uses
considered
include
application
to
vegetable
gardens
and
ornamentals.
Because
there
were
discrepancies
in
the
label
rates
on
products
likely
to
be
used
by
homeowners,
the
residential
exposure
assessment
used
the
agricultural
application
rates.
Exposures
were
estimated
based
on
application
to
a
selection
of
home
garden
vegetables
(
cucurbits,
corn,
and
tomatoes)
and
ornamentals,
which
represent
the
full
range
of
application
rates,
and
also
represent
commodities
commonly
grown
in
home
gardens.
An
application
rate
of
2.4
lb
ai/
A
was
used
for
all
crops
considered,
and
is
the
maximum
rate
for
the
representative
crops.

Handler
Data
and
Assumptions
For
home
gardens,
the
area
treated
per
day
was
assumed
to
be
1000
sq.
feet,
and
is
typical
Agency
practice
based
on
the
National
Home
Garden
Survey.
Application
methods
considered
include
backpack
and
low
pressure
handwand
sprayers.
As
stated
above,
the
application
rate
was
assumed
to
be
2.4
lb
ai/
A
for
a
representative
selection
of
crops.

Exposure
data
used
to
estimate
risks
for
residential
handlers
applying
mancozeb
with
a
low
pressure
handwand
were
based
on
a
study
submitted
for
the
active
ingredient
carbaryl.
Only
the
hand
held
pump
spray
data
were
used.
For
the
backpack
sprayer
scenario,
the
unit
exposure
data
from
The
Pesticide
Handlers
Exposure
Database
(
PHED
v.
1.1)
were
used
as
a
surrogate.
Because
the
study
evaluated
exposures
with
gloves,
a
unit
exposure
value
was
estimated
for
residential
exposures
assuming
no
gloves,
leading
to
less
confidence
in
exposure
and
risk
estimates
for
residential
handlers
using
a
backpack
sprayer.

Dermal
and
inhalation
exposures
were
combined
for
ETU
since
the
toxic
effects
assumed
to
result
from
these
two
routes
of
exposure
were
identical
(
developmental
effects
for
ETU).
For
estimating
cancer
risks,
a
70­
year
life­
span
was
assumed,
with
50
years
of
gardening,
five
exposure
days
per
year,
and
the
standard
70
kg
body
weight
for
applicators.

4.5.1.2
Summary
of
Residential
Handler
Risks
Handler
risks
for
home
gardeners
applying
products
containing
mancozeb
to
vegetables
are
below
the
level
of
concern
for
short­
term
risk
for
mancozeb­
derived
ETU;
in
addition,
cancer
risks
associated
with
ETU
exposure
are
below
the
level
of
concern.
Short­
term
MOEs
for
ETU
are
significantly
higher
than
the
target
MOE
of
1000.
Cancer
risks
are
below
1
x
10­
6.
A
summary
of
ETU
risks
for
home
gardeners
is
presented
in
Table
4.5.
31
Table
4.5.
Home
Gardener
Handler
Exposure
and
Risks
for
Mancozeb
and
ETU.

Exposure
Scenario
Appl.
Rate
(
lb
ai/
acre)
Area
Treated
(
Acre/
Day)
ETU
(
non­
cancer)
ETU
(
Cancer)

Absorbed
Dose
(
mg/
kg/
day)
MOE
LADD
Risk
1)
Backpack
Sprayer
2.4
0.023
(
1000
ft2)
8.1
x
10­
6
620000
6.8
x
10­
8
4
x
10­
9
2)
Low
Pressure
Handwand
4.5
x
10­
5
110000
3.8
x
10­
7
2
x
10­
8
Notes:
Absorbed
Dose
=
combined
dermal
and
inhalation
for
ETU.
MOE
=
Margin
of
Exposure
=
NOAEL/
Absorbed
Dose
[
NOAEL
for
ETU
=
5
mg/
kg/
day]
LADD
=
Lifetime
Average
Daily
Dose
(
the
average
daily
dose
x
(
5
exposure
days/
365
days)*(
50
years/
70
years)
Cancer
Risk
=
LADD
x
0.0601
(
mg/
kg/
day)­
1
4.5.1.3
Home
Garden
Postapplication
Risks
Short­
term
dermal
postapplication
risks
for
adult
and
youth
home
gardeners
are
below
the
level
of
concern
(
i.
e.,
MOEs
exceed
1000)
for
ETU.
Cancer
risks
were
calculated
for
adults
only,
and
were
all
below
5x10­
7,
the
risk
associated
with
hand
harvesting
sweet
corn
on
the
day
of
application.
A
summary
of
postapplication
exposure
and
risk
is
provided
in
Table
4.6.
Only
the
risks
associated
with
the
very
high
exposure
activities
are
shown
for
the
purpose
of
calculating
aggregate
exposure
and
risk
for
ETU
(
food
+
residential
+
water).
Provided
aggregate
risks
for
these
very
high
activities
are
not
of
concern,
then
risks
for
lower
exposure
activities
are
also
not
of
concern.

Table
4.6.
Home
Gardener
Postapplication
Risks
for
ETU
From
Application
of
Mancozeb
Exposure
Scenario
ETU
(
non­
cancer)
ETU
(
Cancer),
Adults
only
Absorbed
Dose
(
mg/
kg/
day)
MOE
Average
Daily
Dose
(
mg/
kg/
day
LADD
Cancer
Risk
Youth
0.00024
29000
N/
A
NA
NA
Adults
0.00031
16000
0.00027
2.7
x
10­
6
1.6
x
10­
7
Notes:
Risks
are
for
pulling,
leaf
thinning,
and
thinning,
cucurbits,
on
the
day
of
application.
All
other
postapplication
risks
for
home
gardeners
were
lower.
Absorbed
Dose
=
Dermal
only
MOE
=
NOAEL/
Absorbed
Dose
[
NOAEL
for
ETU
=
5
mg/
kg/
day
for
adults
and
7
mg/
day
for
youth]
LADD
=
Lifetime
Average
Daily
Dose
(
the
average
daily
dose
x
(
5
exposure
days
per
year/
365
days
per
year)*(
50
years
of
exposure/
70
years
of
life)
Cancer
Risk
=
LADD
x
0.0601
(
mg/
kg/
day)­
1
32
4.5.2
Postapplication
Turf
Risks
Postapplication
ETU
exposures
occur
when
adults
or
children
come
into
contact
with
turf
that
has
been
treated
with
mancozeb
or
maneb.
For
the
EBDC
turf
uses,
three
postapplication
exposure
scenarios
have
been
assessed:

1)
Adults
golfing
on
treated
turf
(
mancozeb
only);
2)
Adult
athletes
playing
on
collegiate
and
professional
athletic
fields
(
mancozeb
only)
2)
Toddlers
playing
on
transplanted
treated
turf
(
mancozeb
and
maneb)

Toddlers'
postapplication
exposure
to
residues
on
treated
lawns
or
turf
consists
of
the
combined
estimates
of
dermal
exposure
from
playing
on
treated
turf
and
incidental
nondietary
ingestion.
The
three
types
of
nondietary
ingestion
considered
include
(
1)
hand­
to­
mouth
(
occurs
when
children
touch
treated
turf
and
then
put
their
hands
in
their
mouths);
(
2)
object­
to­
mouth
(
results
from
children
mouthing
a
handful
of
treated
turf);
and
(
3)
soil
ingestion
(
occurs
when
children
ingest
soil
that
has
been
treated
with
a
pesticide).
These
exposures
are
considered
to
be
shortterm
in
duration,
and
are
also
considered
likely
to
co­
occur.

4.5.2.1
Postapplication
Data
and
Assumptions
In
general,
the
approach
used
to
estimate
postapplication
exposure
to
the
EBDCs
and
ETU
encompassed
typical
Agency
policies
and
assumptions,
and
have
been
summarized
in
Standard
Operating
Procedures
(
guidance
documents),
or
SOPs.

The
registrants
submitted
one
turf
transferrable
residue
(
TTR)
study
for
mancozeb.
This
study
was
conducted
at
sites
in
CA,
PA
and
NC,
in
which
mancozeb
was
applied
with
a
groundboom
sprayer
at
0.6X
to
0.9X
the
maximum
label
rate.
Turf
samples
were
analyzed
up
to
14
days
after
applications
were
made.
The
mancozeb
half­
life
was
1.8
days
at
the
California
site,
3.0
days
at
the
North
Carolina
site
and
6
days
at
the
Pennsylvania
site.
The
California
site
was
irrigated
with
a
total
of
2.5
inches
of
water,
the
North
Carolina
site
received
0.43"
inches
of
rain
on
DAT
3
and
the
PA
site
received
0.15"
of
rain
on
DAT
12.

An
ETU
half­
life
could
not
be
calculated
since
ETU
residues
were
very
low
or
nondetectable.
To
estimate
exposure
from
residues
on
turf,
the
mancozeb
residues
were
assumed
to
be
5%
of
the
application
rate
on
the
day
of
application,
and
subsequent
values
were
calculated
based
on
residue
decline
kinetics.
The
concomitant
ETU
residues
from
mancozeb
applications
were
assumed
to
be
0.61%
of
the
mancozeb
residues,
and
this
was
based
on
dislodgeable
foliar
residue
(
DFR)
studies
in
which
both
mancozeb
and
ETU
were
measured.
The
concomitant
ETU
residues
from
maneb
applications
were
assumed
to
be
2.2%
of
the
maneb
residues,
and
this
was
based
on
DFR
studies
in
which
both
maneb
and
ETU
were
measured.

Other
relevant
assumptions
include:

C
The
mancozeb
TTR
data
was
translated
to
maneb.
33
C
The
half
life
for
the
California
site,
where
irrigation
occurred,
was
used
to
represent
the
dissipation
rate
for
transplanted
turf
because
transplanted
turf
must
be
kept
wet
to
become
established.

C
Three­
year­
old
toddlers
weigh
15
kg.

C
Hand­
to­
mouth
events
occur
20
times/
hour.

C
Saliva
extraction
is
50%
(
i.
e.,
half
the
residue
on
the
hand
is
removed
by
saliva).

C
Typical
transfer
coefficients
for
turf
were
used
(
SOP
for
Residential
Exposure
Assessment);
for
golfers,
the
transfer
coefficient
was
500
cm2/
hour
(
typically
used,
and
a
policy
is
under
development);

C
Toddler
contact
with
treated
turf
lasts
for
2
hours
per
day.

C
Only
the
tees
and
greens
are
routinely
treated
with
EBDCs.

C
One
hour
of
each
round
is
spent
on
the
tees
and
greens.

C
Golfers
play
an
average
of
19
rounds
per
year
based
upon
information
from
the
National
Golf
Foundation
for
the
years
1994
through
2003.

C
The
transfer
coefficient
for
athletes
was
assumed
to
be
14,500
cm2/
hr
for
short
term
exposures
and
7300
cm2/
hr
for
lifetime
exposures.

C
Athletes
were
assumed
to
be
exposed
to
treated
fields
for
two
hours
per
day,
ten
days
per
year
and
ten
years
per
lifetime
4.5.2.2
Postapplication
Risks
for
Adults
on
Turf
The
MOEs
for
the
golfer
and
athlete
turf
scenarios
are
summarized
in
Table
4.7.
The
MOEs
were
calculated
using
day
zero
residues
based
upon
the
maximum
application
rates.
The
MOE
for
golfers
exceeds
the
target
MOE
of
1000
and
the
MOE
for
athletes
(
450)
does
not
exceed
the
target
MOE.

Table
4.7.
ETU
Non­
Cancer
Post­
Application
Risks
for
Adults
Exposed
to
Turf
Treated
with
Mancozeb
Activity
Mancozeb
TTR
(
µ
g/
cm2)
ETU
TTR
(
µ
g/
cm2)
Transfer
Coefficient
(
cm2/
hr)
Hours
per
Day
Exposure
Daily
Dose
C
(
mg/
kg/
day)
MOED
Golf
Athletics
9.76A
9.76A
0.060B
0.060B
500
14500
4.0
2.0
0.00076
0.011
6600
450
A.
Day
0
value
assuming
5%
of
the
applied
amount
(
17.4
lb
ai/
acre)
is
transferable.
B.
Obtained
by
multiplying
the
mancozeb
TTR
by
an
ETU
conversion
factor
of
0.61
percent
C.
Daily
Dose
=
[(
Mancozeb
TTR
*
TC
*
Hrs/
day
*
Mancozeb
Dermal
Absorption
Factor
*
Metabolic
Conversion
factor)
+
(
ETU
TTR
*
TC
*
Hrs/
day
*
ETU
Dermal
Absorption
factor)]/
60
kg
D.
MOE
=
NOAEL/
DOSE
where
the
ETU
NOAEL
=
5
mg/
kg/
day;
target
MOE
is
1000
The
cancer
risks
for
the
golfer
and
athlete
turf
scenarios
are
summarized
in
Table
4.8.
The
cancer
risks
were
calculated
using
seven
day
average
residues
based
upon
a
single
application
of
17.4
lb
ai/
acre.
The
cancer
risks
are
not
of
concern
for
either
golfers
or
athletes.
34
Table
4.8.
ETU
Postapplication
Cancer
Risks
for
Adults
Exposed
to
Turf
Treated
with
Mancozeb
Activity
ETU
TTRA
(
µ
g/
cm2)
TC
(
cm2/
hr)
Hours
per
Day
Daily
DoseB
(
mg/
kg/
day)
Days
Per
Year
Years
of
Exposure
LADDC
(
mg/
kg/
day)
Cancer
Risk
D
Golf
Athletics
0.020
0.032
500
7300
1.0
2.0
5.4e­
05
2.6e­
03
1
1
50
10
1.0
x
10­
7
1.0
x
10­
6
6
x
10­
9
6
x
10­
8
A.
Obtained
by
multiplying
the
mancozeb
TTR
by
an
ETU
conversion
factor
of
0.61
percent
B.
Daily
Dose
=
[(
Mancozeb
TTR
*
TC
*
Hrs/
day
*
Mancozeb
Dermal
Absorption
Factor
*
Metabolic
Conversion
factor)
+
(
ETU
TTR
*
TC
*
Hrs/
day
*
ETU
Dermal
Absorption
factor)]/
70
kg
C.
LADD
=
Daily
Dose
*
(
Days
per
year/
365
days)
*
(
Years
of
Exposure/
70
years
per
lifetime)
D.
Cancer
Risk
=
LADD
*
ETU
Q1
of
0.0601
mg/
kg/
day
4.5.2.3
Postapplication
Risks
for
Toddlers
on
Turf
The
post
application
risk
of
toddlers
exposed
to
ETU
residues
on
sod
farm
turf
treated
with
either
mancozeb
or
maneb
are
summarized
in
Table
4.9.
The
risks
were
calculated
beginning
at
3
days
after
application
to
allow
for
harvesting
and
transplanting
following
the
restricted
entry
interval
(
REI)
of
24
hours.
The
MOEs
from
application
of
maneb
were
calculated
at
the
label
application
rate
of
17.4
lb
ai/
acre
and
the
proposed
rate
of
8.7
lb
ai/
acre.
The
individual
MOEs
were
all
above
the
target
MOEs
with
the
exception
of
the
dermal
MOE
for
ETU
from
maneb
from
the
existing
application
rate.
The
total
MOEs
which
included
dermal,
hand­
to­
mouth,
object
to
mouth
and
soil
ingestion
were
also
below
1000
at
the
existing
PHI
of
1
day.
The
individual
MOEs
for
mancozeb
rise
to
1000
a
PHI
of
1
to
3
days.
If
the
maneb
label
application
rate
of
17.4
lb
ai/
acre
is
used
the
Total
MOE
rises
to
the
target
MOE
with
a
PHI
of
5
days.
If
the
proposed
application
rate
of
8.7
lb
ai/
acre
is
used,
the
Total
MOE
rises
to
the
target
MOE
with
a
PHI
of
3
days.

Table
4.9
­
ETU
Postapplication
Risks
for
Toddlers
Exposed
to
Turf.

Exposure
Pathway
ETU
from
Mancozeb
ETU
from
Maneb
17.4
lb
ai/
A
rate
(
Existing
Label
Rate)
ETU
from
Maneb
8.7
lb
ai/
A
rate
(
Proposed
New
Rate)

MOE
on
Day
3*
PHI
Needed
to
Achieve
an
MOE
of
1000
MOE
on
Day
3*
PHI
Needed
to
Achieve
an
MOE
of
1000
MOE
on
Day
3*
PHI
Needed
to
Achieve
an
MOE
of
1000
Dermal
Hand­
to­
Mouth
Object­
to­
Mouth
Soil
Ingestion
Total
of
Above+
1400
1100
4300
320000
530
1
1
0
0
3
460
1100
3600
24000
300
3
1
0
0
5
920
2200
7200
48000
600
2
0
0
0
3
Table
4.9
­
ETU
Postapplication
Risks
for
Toddlers
Exposed
to
Turf.

Exposure
Pathway
ETU
from
Mancozeb
ETU
from
Maneb
17.4
lb
ai/
A
rate
(
Existing
Label
Rate)
ETU
from
Maneb
8.7
lb
ai/
A
rate
(
Proposed
New
Rate)

MOE
on
Day
3*
PHI
Needed
to
Achieve
an
MOE
of
1000
MOE
on
Day
3*
PHI
Needed
to
Achieve
an
MOE
of
1000
MOE
on
Day
3*
PHI
Needed
to
Achieve
an
MOE
of
1000
35
*
The
current
PHI
is
1
day
because
the
REI
is
24
hours.
+
Total
MOE
=
1/((
1/
Dermal
MOE)+(
1/
HTM
MOE)
+
(
1/
OTM
MOE)
+(
1/
Soil
MOE))
s
5.0
Aggregate
Risk
Assessments
and
Risk
Characterizations
In
accordance
with
the
FQPA,
HED
must
consider
and
aggregate
(
add)
pesticide
exposures
and
risks
from
three
major
sources
or
pathways:
food,
drinking
water,
and
residential
exposures.
In
an
aggregate
assessment,
exposures
from
relevant
sources
are
added
together
and
compared
to
quantitative
estimates
of
hazard
(
e.
g.,
a
NOAEL
or
PAD),
or
the
risks
themselves
can
be
aggregated.
When
aggregating
exposure
and
risk
from
various
sources,
HED
considers
both
the
route
and
duration
of
exposure.
Exposure
to
ETU
can
occur
in
residential
and
recreational
settings.
The
mancozeb
and
maneb
uses
on
sod
farms
and
golf
courses
result
in
post
application
exposure
to
adults
while
golfing,
and
for
toddlers
contacting
treated
turf
that
was
transplanted
from
a
sod
farm.

For
ETU,
aggregate
exposure
sources
include
dietary
food,
drinking
water,
home
gardening
activities,
golfing
and
athletics.
The
residential
and
recreational
exposures
are
expected
to
be
short­
term
exposures,
so
an
intermediate­
term
aggregate
assessment
was
not
conducted.
The
following
aggregate
risk
assessments
have
been
completed:

(
1)
ETU
acute
aggregate
(
food
+
water)
(
3)
ETU
short­
term
aggregate
(
food
+
water
+
golfing
or
gardening)
(
2)
ETU
chronic
aggregate
(
food
+
water)
(
4)
ETU
cancer
aggregate
(
food
+
water
+
golfing
or
gardening
or
athletics).

These
aggregate
risk
assessments
are
representative
exposures
that
are
expected
to
co­
occur.

The
ETU
surface
and
ground
water
monitoring
data
are
considered
adequate
to
generate
quantitative
surface
and
ground
water
drinking
water
chronic
exposure
estimates.
The
surface
water
monitoring
data,
combined
with
PRZM­
EXAMs
modeling,
indicate
a
concentration
of
0.1
ppb
should
be
used
to
calculate
aggregate
chronic
and
cancer
exposure
and
risk.
The
ETU
ground
water
concentration
(
0.21
ppb)
was
taken
from
a
targeted
monitoring
study;
use
of
this
value
to
calculate
aggregate
risk
provides
an
upper
bound
estimate
of
exposure
through
drinking
water
from
ground
water
sources.
36
5.1
ETU
Acute
Aggregate
Risk
Assessment
(
Food
+
Water)

Acute
risks
for
aggregate
food
and
water
exposure
were
calculated
on
a
semi­
probabilistic
basis
in
DEEM­
FCID
using
the
full
range
of
food
residue
data
and
the
acute
EDWC
point
estimate
of
25.2
ppb
for
the
drinking
water
concentration.
Acute
aggregate
risks
were
calculated
only
for
females
13­
49
because
the
aPAD
is
based
upon
developmental
effects
which
are
only
applicable
to
this
population
subgroup.
The
acute
aggregate
exposures
are
not
of
concern
because
the
99.9th
percentile
exposure
(
87%
of
the
aPAD)
is
less
than
100%
of
the
aPAD.
The
acute
risk
calculations
are
included
in
Table
5.1.

Table
5.1
­
ETU
Acute
Aggregate
Risk
Population
Subgroup
aPAD
(
mg/
kg/
day)
95th
Percentile
99th
Percentile
99th
Percentile
Exposure
(
mg/
kg/
day)
%
aPAD
Exposure
(
mg/
kg/
day)
%
aPAD
Exposure
(
mg/
kg/
day)
%
aPAD
Females
13­
49
yrs
old
0.005
0.001304
26
0.002148
43
0.004331
87
Notes:
aPAD
=
0.005
mg/
kg/
day
Exposure
includes
food
and
drinking
water.
Drinking
water
exposure
is
based
upon
the
surface
water
EDWC
of
25.2
ppb
5.2
Short­
Term
Aggregate
Exposure
and
Risk
The
short
term
aggregate
risks
were
calculated
for
adults
by
aggregating
chronic
food
exposure,
chronic
drinking
water
exposure
and
golfing
or
gardening
exposures.
Toddler
exposure
to
transplanted
turf
was
not
aggregated
with
food
and
water
because
the
turf
scenario
is
a
rare
event
and
the
Agency
does
not
believe
it
is
appropriate
to
aggregate.
The
short
term
risks
were
calculated
for
the
most
sensitive
adult
population
(
females
13­
49)
because
the
endpoint
is
based
upon
developmental
effects.
The
MOEs
range
from
6200
to
62000
as
shown
in
Table
5.2
and
indicate
that
the
short
term
risks
are
not
of
concern.
Note
that
the
short­
term
risks
to
athletes
were
not
aggregated
because
they
exceed
the
level
of
concern
before
aggregation.

Table
5.2
­
ETU
Short­
Term
Aggregate
Post­
application
Risk
Scenario
Absorbed
Dose
(
µ
g/
kg/
day)
Dietary
Exposure
Aggregate
Exposure/
Risk
Food
(
µ
g/
kg/
day)
Water
(
µ
g/
kg/
day)
Exposure
(
µ
g/
kg/
day)
MOE
Golf
Home
Garden
Handler
(
Handwand)
0.76
0.045
0.033
0.033
0.003
0.003
0.80
0.08
6200
62000
Table
5.2
­
ETU
Short­
Term
Aggregate
Post­
application
Risk
Scenario
Absorbed
Dose
(
µ
g/
kg/
day)
Dietary
Exposure
Aggregate
Exposure/
Risk
Food
(
µ
g/
kg/
day)
Water
(
µ
g/
kg/
day)
Exposure
(
µ
g/
kg/
day)
MOE
37
Notes:
Absorbed
Dose
=
Dermal,
µ
g/
kg/
day.
(
Tables
4.6
and
4.7)
Dietary
Food
exposure
=
chronic
food
exposure
females
13­
49,
µ
g/
kg/
day
(
Table
4.3)
Dietary
Water
exposure
=
(
chronic
surface
water
EEC
of
0.1
ppb
*
2
l/
day)/
60
kg
Aggregate
Exposure
=
Absorbed
dose
+
food
exposure
(
µ
g/
kg/
day)
Aggregate
MOE
(
Margin
of
Exposure)
=
NOAEL/(
Aggregate
Exposure
*
0.001
mg/
µ
g)
[
Short­
term
NOAEL
for
ETU
=
5
mg/
kg/
day]

5.3
ETU
Chronic
Aggregate
Risk
Assessment
The
aggregate
chronic
risk
were
calculated
using
food
and
water
exposure
only
because
golfing,
athletic
field
and
toddler
transplanted
turf
exposure
scenarios
were
considered
to
occur
only
on
a
short
term
basis.
The
ETU
surface
water
and
ground
water
residues
of
0.1
and
0.21
ppb,
respectively,
were
incorporated
into
a
dietary
(
water
only)
exposure
assessment
using
the
DEEMFCID
 
model.
The
resulting
exposures
were
then
added
to
the
chronic
exposure
from
food.
The
aggregate
chronic
risks
are
below
HED's
level
of
concern
(
100
%
cPAD)
for
the
general
US
population
and
all
other
population
subgroups.
The
most
highly
exposed
population
subgroup
is
children
1­
2
years
old,
with
aggregate
risks
of
56­
58
%
cPAD.
Exposure
from
food
was
approximately
an
order
of
magnitude
greater
than
exposure
from
drinking
water.
The
aggregate
chronic
risks
are
summarized
in
Table
5.3.

Table
5.3.
Results
of
Chronic
Dietary
Exposure
Analysis
for
Food
and
Drinking
Water
Population
Subgroup
cPAD
(
mg/
kg/
day)
Surface
Water
EDWC
(
0.1
ppb)
Groundwater
EDWC
(
0.21
ppb)

Exposure
(
mg/
kg/
day)
%
cPAD
Exposure
(
mg/
kg/
day)
%
cPAD
General
U.
S.
Population
0.0002
0.000033
17
0.000035
18
All
Infants
(<
1
year
old)
0.0002
0.000068
33
0.000076
38
Children
1­
2
years
old
0.0002
0.000111
56
0.000115
58
Children
3­
5
years
old
0.0002
0.000075
37
0.000078
39
Children
6­
12
years
old
0.0002
0.000035
17
0.000037
18
Youth
13­
19
years
old
0.0002
0.000023
12
0.000024
12
Adults
20­
49
years
old
0.0002
0.000027
13
0.000029
15
Females
13­
49
years
old
0.0002
0.000028
14
0.000030
15
Table
5.3.
Results
of
Chronic
Dietary
Exposure
Analysis
for
Food
and
Drinking
Water
Population
Subgroup
cPAD
(
mg/
kg/
day)
Surface
Water
EDWC
(
0.1
ppb)
Groundwater
EDWC
(
0.21
ppb)

Exposure
(
mg/
kg/
day)
%
cPAD
Exposure
(
mg/
kg/
day)
%
cPAD
38
Adults
50+
years
old
0.0002
0.000029
15
0.000031
16
**
The
values
for
the
highest
exposed
population
for
each
type
of
risk
assessment
are
bolded.

5.4
ETU
Aggregate
Cancer
Risk
The
cancer
risks
were
aggregated
using
the
food
and
drinking
water
doses
for
the
general
population
and
the
food,
water
and
recreational
doses
for
golfers,
home
gardeners
and
athletes.
The
average
daily
dose
was
used
for
food
and
water
exposures
and
the
lifetime
average
daily
dose
(
LADD)
was
used
for
the
recreational
exposures.
The
aggregate
doses
were
multiplied
times
the
potency
factor
for
ETU,
0.0601
(
mg/
kg/
day)­
1
to
determine
the
cancer
risks
which
are
summarized
in
Table
5.4.
These
risks
are
in
the
range
of
2.0
x
10­
6
to
2.7
x
10­
6
and
the
food
exposure
is
the
largest
contributor.

Table
5.4
ETU
Aggregate
Cancer
Risks
Exposure
Sources
Residential
Exposure
LADD
(
µ
g/
kg/
day)
Dietary
Exposure
Aggregate
Exposure
Food
(
µ
g/
kg/
day)
Water
(
µ
g/
kg/
day)
Exposure
(
µ
g/
kg/
day)
Cancer
Risk
Based
upon
ground
water
EDWC
of
0.21
µ
g/
L
Food
+
Water
N/
A
0.031
0.0044
0.0354
2.1e­
06
Food
+
Water
+
Golf
0.0010
0.031
0.0044
0.0364
2.2e­
06
Food
+
Water
+
Home
Garden
Handler
0.00038
0.031
0.0044
0.0358
2.1e­
06
Food
+
Water
+
Home
Garden
Post
Application
0.0088
0.031
0.0044
0.0442
2.7e­
06
Food
+
Water
+
Athletics
0.010
0.031
0.0044
0.0454
2.7e­
06
Based
upon
surface
water
EDWC
of
0.10
µ
g/
L
Food
+
Water
N/
A
0.031
0.0020
0.0330
2.0e­
06
Food
+
Water
+
Golf
0.001
0.031
0.0020
0.0340
2.0e­
06
Food
+
Water
+
Home
Garden
Handler
0.00038
0.031
0.0020
0.0334
2.0e­
06
Table
5.4
ETU
Aggregate
Cancer
Risks
Exposure
Sources
Residential
Exposure
LADD
(
µ
g/
kg/
day)
Dietary
Exposure
Aggregate
Exposure
Food
(
µ
g/
kg/
day)
Water
(
µ
g/
kg/
day)
Exposure
(
µ
g/
kg/
day)
Cancer
Risk
39
Food
+
Water
+
Home
Garden
Post
Application
0.0088
0.031
0.0020
0.0418
2.5e­
06
Food
+
Water
+
Athletics
0.01
0.031
0.0020
0.0430
2.6e­
06
Notes:
LADD
=
Lifetime
Average
Daily
Dose
from
Tables
4.6
and
4.8
Aggregate
Exposure
=
Residential
LADD
+
food
exposure
+
water
exposure
Cancer
risk
=
Aggregate
exposure
x
0.001
mg/
µ
g
x
0.0601
(
mg/
kg/
day)­
1
6.0
Cumulative
Exposure
and
Risk
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."

The
Agency
has
concluded
that
N­
methyl
carbamates
subgroup
should
be
designated
as
a
common
mechanism
group
(
CMG)
based
on
their
shared
structural
characteristics
and
similarity,
and
on
their
shared
ability
to
inhibit
acetylcholinesterase
(
Report
of
9/
22/
99
SAP
Meeting).
Thiocarbamates
and
dithiocarbamates
(
which
include
the
EBDCs)
have
not
been
included
in
the
CMG
because
they
do
not
share
cholinesterase
inhibition
as
a
common
principal
mechanism
of
toxicity.

During
previous
Special
Review
of
the
EBDCs
(
metiram,
maneb
and
mancozeb),
the
Agency
considered
the
three
active
ingredients
to
be
related
due
to
the
common
effect,
thyroid
cancer,
resulting
from
formation
of
the
common
metabolite,
ETU;
exposure
to
residues
in
and
on
crops
as
well
as
in
vivo
conversion
of
EBDCs
to
ETU
was
included
in
the
assessments.

In
2001,
the
Agency
proposed
a
common
mechanism
of
toxicity
for
all
dithiocarbamates
based
on
neuropathology
related
to
CS
2
formation.
However,
following
public
comment
and
SAP
review
of
the
data,
OPP
concluded
there
was
no
support
for
grouping
dithiocarbamates,
including
EBDCs,
based
on
a
common
mechanism
for
neuropathology.
No
determination
of
a
common
toxic
effect
or
mechanism
of
toxicity
has
been
made
for
acute
or
chronic
non­
cancer
risks
from
EBDCs.
No
other
dithiocarbamates
are
included
in
the
risk
assessment
because
they
do
not
produce
the
metabolite
ETU.

7.0
Occupational
Exposure
40
The
Occupational
and
Residential
(
ORE)
aspects
of
the
Human
Health
Risk
Assessments
have
been
completed
for
each
of
the
EBDC
fungicides.
These
risk
assessments
can
be
identified
by
the
following
information:

C
Mancozeb:
Occupational
and
Residential
Exposure
Assessment
and
Recommendations
for
the
Reregistration
Eligibility
Decision
Document.
PC
Code
014504;
DP
Barcode:
D
D305813.
Author:
Tim
Dole;
June
2005
°
Maneb:
Occupational
and
Residential
Exposure
Assessment
and
Recommendations
for
the
Reregistration
Eligibility
Decision
Document.
PC
Code
014505;
DP
Barcode:
D307983.
Author:
Tim
Dole;
Issued:
June
2005
°
Metiram:
Occupational
and
Residential
Exposure
Assessment
and
Recommendations
for
the
Reregistration
Eligibility
Decision
Document.
PC
Code
014601;
DP
Barcode:
D307986.
Author:
Tim
Dole;
June
2005.

In
each
of
these
assessments
the
risks
of
the
parent
EBDC
and
the
degradate
ETU
were
considered.
With
the
exception
of
chronic
ETU
exposures,
the
risks
of
exposure
to
the
parent
EBDCs
were
generally
greater
than
the
risks
of
exposure
to
ETU.
The
greatest
handler
risks
involve
the
mixing
and
loading
of
wettable
powder
formulations
and
these
risks
can
be
mitigated
by
using
an
alternate
formulation
such
as
dry
flowable
or
by
packaging
the
powder
in
water
soluble
bags.
The
greatest
post
application
risks
involve
chronic
exposures
that
occur
during
pruning,
thinning
or
hand
harvesting
cut
flowers
and
short
term
exposures
that
occur
during
the
pruning
of
pome
fruit
trees.
It
may
be
possible
to
refine
these
risks
based
upon
use
data,
dislodgeable
foliar
residue
data
and
post
application
worker
exposure
data.
Because
the
amount
of
EBDC
that
can
be
applied
to
a
crop
per
season
is
limited,
the
risks
for
a
combined
EBDC
application
would
not
be
worse
than
for
the
worst
case
single
EBDC
application.
For
example,
the
amount
of
EBDC
that
can
be
applied
to
apple
trees
using
the
extended
schedule
is
16.8
lb
ai
per
season
regardless
of
whether
mancozeb,
maneb
or
metiram
are
used
alone
or
in
some
combination.
The
cancer
risks
for
mixing
and
loading
wettable
powder
for
airblast
application
to
apple
trees
are
1.8
x
10­
5
for
maneb
and
1.0
x
10­
5
for
mancozeb
and
for
mixing
and
loading
dry
flowable
are
3.6
x
10­
7
for
metiram
(
metiram
is
only
formulated
as
a
dry
flowable).
These
risks
are
based
upon
the
assumption
of
30
days
exposure
per
year
during
a
35
year
career.
If
some
combination
of
maneb,
mancozeb
and
metiram
were
used
the
resulting
risk
would
fall
between
3.6
x
10­
7
and
1.8
x
10­
5.
Although
the
assumption
could
be
made
that
the
aggregate
ETU
cancer
risk
would
be
the
sum
of
the
risks
for
mancozeb,
maneb
and
metiram,
this
assumption
may
not
be
valid
because
the
use
data
indicate
that
there
is
limited
overlap
in
use
patterns.

Given
the
above
information,
the
assumption
of
thirty
days
exposure
per
year
for
each
individual
EBDC
is
protective
of
combined
EBDC
use
and
a
separate
aggregate
assessment
of
occupational
exposure
to
ETU
is
not
required.

8.0
Data
Needs/
Label
Requirements
41
The
data
needs
for
each
individual
EBDC
and
the
corresponding
exposures
to
ETU
are
discussed
in
the
risk
assessments
for
each
individual
EBDC.
The
data
gaps
for
ETU
toxicology
studies
include
a
developmental
neurotoxicity
study,
developmental
toxicity
study
in
rabbits,
2­
generation
reproduction
study
in
rats,
and
a
comparative
study
for
thyroid
toxicity
in
adults
and
offspring.

9.0
Supporting
Documentation
Supporting
information
for
this
risk
assessment
includes
the
following
documents:
1)
Outcome
of
the
HED
Metabolism
Assessment
Review
Committee
Meeting
of
1/
16/
02,
C.
Swartz,
12/
3/
02,
TXR
#
0050408.
2)
Metiram.
Health
Effects
Division
(
HED)
Human
Health
Risk
Assessment
to
Support
Reregistration.
DP
Barcode
No.
D291661
,
K.
Farwell,
June
2005
3)
Mancozeb.
Health
Effects
Division
(
HED)
Human
Health
Risk
Assessment
to
Support
Reregistration.
DP
Barcode
No.
D317371
K.
Farwell,
October
14,
2004.
4)
Maneb.
Revised
Health
Effects
Division
(
HED)
Human
Health
Risk
Assessment
to
Support
Reregistration.
Chemical
ID
No.
014505.
List
A
Reregistration
Case
No.
0642.
DP
Barcode
No.
D295409,
C.
Olinger,
June
2005.
5)
Mancozeb,
Maneb
and
Metiram:
Revised
Aggregate
Dietary
Assessment
of
the
Common
Metabolite/
Degredate
Ethylene
Thiorea
(
ETU)
to
Support
Reregistration
including
Aggregate
ETU
Drinking
Water
Assessment
Anticipated
Residues
and
Dietary
Exposure
Assessment,
F.
Fort,
10/
26/
04,
DP
Barcode
No.
D305131.
6)
Hazard
Characterization
for
Ethylene
Thiourea,
Kit
Farwell,
D.
V.
M.
1/
28/
02,
DP
Barcode
D280427
7)
Ethylene
Thiourea.
3rd
Report
of
the
Hazard
Identification
Assessment
Review
Committee,
Kit
Farwell,
D.
V.
M.,
5/
28/
03,
TXR
NO.
0051924
8)
Revison
No.
2:
Estimated
Drinking
Water
Concentrations
of
Ethylenebisdithiocarbamate
(
EBDC)
Degradate
Ethylenethiourea
(
ETU)
for
Use
in
Human
Health
Risk
Assessment
Ronald
Parker
and
Mohammed
Ruhman,
EFED,
8/
26/
04.
42
Appendix
1.
Usage
Information
Screening
Level
Usage
Analysis
for
Maneb
What
is
a
Screening
Level
Usage
Analysis
(
SLUA)?

!
Available
estimates
of
pesticide
usage
data
for
a
particular
active
ingredient
that
is
used
on
agricultural
crops
in
the
United
States.

What
does
it
contain?

!
Agricultural
use
sites
(
crops)
that
the
pesticide
is
reported
to
be
used
on
!
Pesticide
usage
information
on
the
national
level
for
the
United
States.

!
Annual
percent
of
crop
treated
(
average
&
maximum)
for
each
agricultural
use
site.

!
Average
annual
pounds
of
the
pesticide
applied
for
each
agricultural
use
site.

What
assumptions
can
I
make
about
the
data
reported?

!
Average
pounds
of
active
ingredient
applied
­
Values
are
calculated
by
merging
pesticide
usage
data
sources
together;
averaging
by
year,
averaging
across
all
years,
&
then
rounding.
Note:
If
the
estimated
value
is
less
than
500,
then
that
value
is
labeled
<
500.
Estimated
values
between
500
&
<
1,000,000
are
rounded
to
1
significant
digit.
Estimated
values
of
1,000,000
or
greater
are
rounded
to
2
significant
digits.)

!
Average
percent
of
crop
treated
­
Values
are
calculated
by
merging
data
sources
together;
averaging
by
year,
averaging
across
all
years,
&
rounding
to
the
nearest
multiple
of
5.
Note:
If
the
estimated
value
is
less
than
1,
then
the
value
is
labeled
<
1.

!
Maximum
percent
of
crop
treated
­
Value
is
the
single
maximum
value
reported
across
all
data
sources,
across
all
years,
&
rounded
up.
Note:
If
the
estimated
value
is
less
than
2.5,
then
the
value
is
labeled
<
2.5.

What
are
the
data
sources
used?

!
USDA­
NASS
(
United
States
Department
of
Agriculture's
National
Agricultural
Statistics
Service)
 
pesticide
usage
data
from
1998
to
2003.

!
NCFAP
(
National
Center
for
Food
and
Agricultural
Policy)
 
pesticide
usage
data
from
1997
&
is
only
used
if
data
is
not
available
from
the
other
sources.

!
Private
pesticide
market
research
 
pesticide
usage
data
from
1998
to
2003.

What
are
the
limitations
to
the
data?

!
Registered/
labeled
uses
may
exist
but
are
not
surveyed
by
the
available
data
sources.

!
Lack
of
reported
usage
data
for
the
pesticide
on
a
crop
does
not
imply
zero
usage.

!
Usage
data
on
a
particular
site
may
be
noted
in
data
sources,
but
not
quantified.
In
these
instances,
no
usage
would
be
reported
in
the
SLUA
for
that
use
site.

!
Non­
agricultural
use
sites
(
e.
g.,
turf,
post­
harvest,
mosquito
control,
etc.)
are
not
reported
in
the
SLUA.
A
separate
request
must
be
made
to
receive
these
estimates.

Who
do
I
contact
for
further
information
and/
or
questions
on
this
SLUA?

!
Jenna
Carter,
Botanist,
BEAD
43
Screening
Level
Estimates
of
Agricultural
Uses
of
Maneb
Sorted
Alphabetically
Crop
Lbs.
A.
I.
Percent
Crop
Treated
Avg
Max
1
Almonds
300,000
10
15
2
Apples
40,000
<
1
5
3
Beans,
Dry
10,000
<
1
<
2.5
4
Beans,
Green
8,000
5
15
5
Broccoli
20,000
5
15
6
Brussels
Sprouts
(*
CA)
1,038
21
32
7
Cabbage
40,000
15
15
8
Cantaloupes
3,000
9
Carrots
3,000
<
1
<
2.5
10
Cauliflower
5,000
5
10
11
Celery
3,000
5
5
12
Collards
4,000
10
25
13
Corn
(
Field)
<
500
<
1
<
1
14
Cucumber
30,000
5
5
15
Dry
Beans/
Peas
20,000
<
1
<
2.5
16
Eggplant
7,000
55
65
17
Garlic
30,000
25
25
18
Grapes
20,000
<
1
5
19
Greens,
Mustard
2,000
5
5
20
Kale
1,000
5
5
21
Lettuce
600,000
65
75
22
Onions
70,000
10
20
23
Pears
5,000
<
1
<
2.5
24
Peppers
200,000
30
45
25
Potatoes
100,000
5
10
26
Pumpkins
4,000
5
5
27
Spinach
10,000
15
45
28
Squash
10,000
5
15
29
Sugar
Beets
40,000
<
1
5
30
Sweet
Corn
10,000
<
1
<
2.5
31
Tomatoes
100,000
5
10
32
Walnuts
300,000
30
35
33
Watermelons
20,000
5
10
34
Wheat
<
500
<
1
<
1
44
Screening
Level
Usage
Analysis
for(
Maneb)

What
is
a
Screening
Level
Usage
Analysis
(
SLUA)?
·
A
Available
estimates
of
pesticide
usage
data
for
a
particular
active
ingredient
that
is
used
on
agricultural
crops
in
the
United
States.

What
does
it
contain?
·
A
Pesticide
usage
data
for
a
single
active
ingredient
only.
·
A
Agricultural
use
sites
(
crops)
that
the
pesticide
is
reported
to
be
used
on
·
A
Pesticide
usage
information
on
the
national
level
for
the
United
States.
·
A
Annual
percent
of
crop
treated
(
average
&
maximum)
for
each
agricultural
use
site.
·
A
Average
annual
pounds
of
the
pesticide
applied
for
each
agricultural
use
site.

What
assumptions
can
I
make
about
the
data
reported?
·
A
Average
pounds
of
active
ingredient
applied
­
Values
are
calculated
by
merging
pesticide
usage
data
sources
together;
averaging
by
year,
averaging
across
all
years,
&
then
rounding.
Note:
If
the
estimated
value
is
less
than
500,
then
that
value
is
labeled
<
500.
Estimated
values
between
500
&
<
1,000,000
are
rounded
to
1
significant
digit.
Estimated
values
of
1,000,000
or
greater
are
rounded
to
2
significant
digits.)
·
A
Average
percent
of
crop
treated
­
Values
are
calculated
by
merging
data
sources
together;
averaging
by
year,
averaging
across
all
years,
&
rounding
to
the
nearest
multiple
of
5.
Note:
If
the
estimated
value
is
less
than
1,
then
the
value
is
labeled
<
1.
·
A
Maximum
percent
of
crop
treated
­
Value
is
the
single
maximum
value
reported
across
all
data
sources,
across
all
years,
&
rounded
up.
Note:
If
the
estimated
value
is
less
than
2.5,
then
the
value
is
labeled
<
2.5.

What
are
the
data
sources
used?
·
A
USDA­
NASS
(
United
States
Department
of
Agriculture''
s
National
Agricultural
Statistics
Service)
  
pesticide
usage
data
from
1998
to
2003.
·
A
NCFAP
(
National
Center
for
Food
and
Agricultural
Policy)
  
pesticide
usage
data
from
1997
&
is
only
used
if
data
is
not
available
from
the
other
sources.
·
A
Private
pesticide
market
research
  
pesticide
usage
data
from
1998
to
2003.

What
are
the
limitations
to
the
data?
·
A
Registered/
labeled
uses
may
exist
but
are
not
surveyed
by
the
available
data
sources.
·
A
Lack
of
reported
usage
data
for
the
pesticide
on
a
crop
does
not
imply
zero
usage.
·
A
Usage
data
on
a
particular
site
may
be
noted
in
data
sources,
but
not
quantified.
In
these
instances,
no
usage
would
be
reported
in
the
SLUA
for
that
use
site.
·
A
Non­
agricultural
use
sites
(
e.
g.,
turf,
post­
harvest,
mosquito
control,
etc.)
are
not
reported
in
the
SLUA.
A
separate
request
must
be
made
to
receive
these
estimates.

Who
do
I
contact
for
further
information
and/
or
questions
on
this
SLUA?
·
A
(
Jenna
Carter,
Botanist,
BEAD)
·
A
((
703)
308­
8370,
carter.
jenna@
epa.
gov)
45
Crop
Pounds
Active
Ingredient
Average
Percent
Crop
Treated
Maximum
Percent
Crop
Treated
Almonds
Apples
Beans,
Dry
(
NCFAP
'
97)
Beans,
Green
Broccoli
Brussels
Sprouts
(
NCFAP
'
97)
Cabbage
Cantaloupes
Carrots
Cauliflower
Celery
Collards
Cucumbers
Dry
Beans/
Peas
Eggplant
Garlic
Grapes
Greens,
Mustard
Kale
Lettuce
Onions
Pears
Peppers
Potatoes
Pumpkins
Spinach
Squash
Sugar
Beets
Sweet
Corn
Tomatoes
Walnuts
Watermelons
300,000
40,000
10,000
8,000
20,000
<
500
40,000
3,000
3,000
5,000
3,000
4,000
40,000
20,000
7,000
30,000
20,000
2,000
1,000
600,000
70,000
5,000
200,000
100,000
4,000
10,000
10,000
40,000
10,000
100,000
300,000
20,000
10
<
1
<
1
5
5
10
15
<
1
<
1
5
5
10
15
<
1
55
25
<
1
5
5
65
10
<
1
30
5
5
15
5
<
1
<
1
5
30
5
15
5
NR
15
15
15
<
2.5
5
10
5
10
25
<
2.5
65
25
5
5
5
75
20
<
2.5
45
10
5
45
15
5
<
2.5
10
35
10
46
Screening
Level
Usage
Analysis
for
(
Metiram)

What
is
a
Screening
Level
Usage
Analysis
(
SLUA)?

·
A
Available
estimates
of
pesticide
usage
data
for
a
particular
active
ingredient
that
is
used
on
agricultural
crops
in
the
United
States.

What
does
it
contain?
·
A
Pesticide
usage
data
for
a
single
active
ingredient
only.
·
A
Agricultural
use
sites
(
crops)
that
the
pesticide
is
reported
to
be
used
on
·
A
Pesticide
usage
information
on
the
national
level
for
the
United
States.

·
A
Annual
percent
of
crop
treated
(
average
&
maximum)
for
each
agricultural
use
site.

·
A
Average
annual
pounds
of
the
pesticide
applied
for
each
agricultural
use
site.

What
assumptions
can
I
make
about
the
data
reported?

·
A
Average
pounds
of
active
ingredient
applied
­
Values
are
calculated
by
merging
pesticide
usage
data
sources
together;
averaging
by
year,
averaging
across
all
years,
&
then
rounding.
Note:
If
the
estimated
value
is
less
than
500,
then
that
value
is
labeled
<
500.
Estimated
values
between
500
&
<
1,000,000
are
rounded
to
1
significant
digit.
Estimated
values
of
1,000,000
or
greater
are
rounded
to
2
significant
digits.)
·
A
Average
percent
of
crop
treated
­
Values
are
calculated
by
merging
data
sources
together;
averaging
by
year,
averaging
across
all
years,
&
rounding
to
the
nearest
multiple
of
5.
Note:
If
the
estimated
value
is
less
than
1,
then
the
value
is
labeled
<
1.
·
A
Maximum
percent
of
crop
treated
­
Value
is
the
single
maximum
value
reported
across
all
data
sources,
across
all
years,
&
rounded
up.
Note:
If
the
estimated
value
is
less
than
2.5,
then
the
value
is
labeled
<
2.5.

What
are
the
data
sources
used?
·
A
USDA­
NASS
(
United
States
Department
of
Agriculture''
s
National
Agricultural
Statistics
Service)
  
pesticide
usage
data
from
1998
to
2003.
·
A
NCFAP
(
National
Center
for
Food
and
Agricultural
Policy)
  
pesticide
usage
data
from
1997
&
is
only
used
if
data
is
not
available
from
the
other
sources.
·
A
Private
pesticide
market
research
  
pesticide
usage
data
from
1998
to
2003.

What
are
the
limitations
to
the
data?

·
A
Registered/
labeled
uses
may
exist
but
are
not
surveyed
by
the
available
data
sources.

·
A
Lack
of
reported
usage
data
for
the
pesticide
on
a
crop
does
not
imply
zero
usage.

·
A
Usage
data
on
a
particular
site
may
be
noted
in
data
sources,
but
not
quantified.
In
these
instances,
no
usage
would
be
reported
in
the
SLUA
for
that
use
site.
47
·
A
Non­
agricultural
use
sites
(
e.
g.,
turf,
post­
harvest,
mosquito
control,
etc.)
are
not
reported
in
the
SLUA.
A
separate
request
must
be
made
to
receive
these
estimates.

Who
do
I
contact
for
further
information
and/
or
questions
on
this
SLUA?
·
A
(
Jenna
Carter,
Botanist,
BEAD)
·
A
((
703)
308­
8370,
carter.
jenna@
epa.
gov)

Screening
Level
Estimates
of
Agricultural
Uses
of
Metiram
Sorted
Alphabetically
OBS
Crop
Lbs.
A.
I.
Percent
Crop
Ttd.
Avg.
Max.
1
Apples
500,000
15
25
2
Asparagus
1,000
<
1
<
2.5
3
Peaches
2,000
<
1
<
2.5
4
Pears
<
500
5
Potatoes
400,000
10
10
6
Squash
<
500
<
1
<
2.5
48
Quantitative
Usage
Analysis
for
Mancozeb
Case
Number:
0643
PC
Code:
14504
Date:
November
1,
2002
Analyst:
Frank
Hernandez
Based
on
available
pesticide
survey
usage
information
for
the
years
of
1992
through
2001,
an
annual
estimate
of
mancozeb
total
domestic
usage
averaged
approximately
six
million
three
hundred
thousand
pounds
of
active
ingredient
(
a.
i.)
for
over
one
million
six
hundred
thousand
acres
treated.

Mancozeb
is
a
fungicide
with
its
largest
markets
in
terms
of
total
pounds
active
ingredient
allocated
to
potatoes
(
31%),
fresh
tomatoes
(
14%),
apples
(
14%),

watermelons
(
5%),
grapes
(
5%),
and
onions
(
4%).
Most
of
the
usage
is
in
FL,
ME,
MI,
MN,
ND,
NY,
VA,
VT,
WA,
and
WI.

Crops
with
a
high
percentage
of
the
total
U.
S.
planted
acres
treated
include
fresh
tomatoes
(
49%),
squash
(
41%),
onions
(
39%),
potatoes
(
36%),
and
pears
(
32%).
Crops
with
less
than
1
percent
of
the
crop
treated
include
alfalfa,
almonds,
avocados,
barley,
dry
beans,
cherries,
corn,
cotton,
grapefruit,
lemons,

oranges,
pecans,
plums
and
prunes,
rice,
soybeans,
sunflower,
walnut,
wheat,
and
woodland.
49
Site
Acres
Grown
(
000)
Acres
Treated
(
000)
%
of
Crop
Treated
LB
AI
Applied
(
000)
Average
Application
Rate
States
of
Most
Usage
Wtd
Avg
Est
Max
Wtd
Avg
Est
Max
Wtd
Avg
Est
Max
lb
ai/

acre/
y
r
#
appl
/
yr
lb
ai/

A/
appl
(%
of
total
lb
ai
used
on
this
site)

Alfalfa
23,950
1
2
0.0
0.0
2
3
1.3
1.0
1.3
AZ
ID
CA
95%

Almonds
431
2
6
0.5
1.3
5
11
2.3
1.3
1.8
CA
100%

Apples
587
150
240
25.6
40.9
890
1,870
5.9
3.3
1.8
NY
MI
WA
MO
65%

Asparagus
90
14
31
15.6
34.4
49
127
3.5
1.7
2.0
MI
WA
80%

Avocados
82
0
3
0.2
3.6
1
14
4.5
4.5
1.0
FL
100%

Barley
7,625
15
68
0.2
0.9
21
85
1.4
1.1
1.2
ND
MN
80%

Beans,
Dry
1,802
9
24
0.5
1.3
12
38
1.3
1.0
1.3
ND
MN
85%

Beans,
Snap,
Fresh
78
5
14
6.4
17.9
16
48
3.2
3.2
1.0
FL
100%

Cabbage
91
9
18
9.9
19.8
42
108
4.7
7.1
0.7
FL
GA
90%

Cantaloupes
121
10
12
7.9
9.9
9
19
1.0
1.0
1.0
MD
NC
GA
TX
85%

Carrots
110
9
14
8.3
13.1
10
20
1.1
1.4
0.8
FL
MI
100%

Cherries
132
0
1
0.4
1.0
1
4
2.4
2.2
1.1
WI
WA
NY
90%

Corn
71,264
9
28
0.0
0.0
48
145
5.3
3.6
1.5
WI
80%

Cotton
12,379
28
97
0.2
0.8
57
142
2.0
1.1
1.8
CA
AR
AZ
NC
85%

Cucumbers
157
28
51
17.8
32.5
180
420
6.4
1.0
6.4
SC
FL
GA
VA
80%

Eggplant
6
0
1
6.6
13.0
5
14
13.2
8.5
1.6
FL
90%
Site
Acres
Grown
(
000)
Acres
Treated
(
000)
%
of
Crop
Treated
LB
AI
Applied
(
000)
Average
Application
Rate
States
of
Most
Usage
Wtd
Avg
Est
Max
Wtd
Avg
Est
Max
Wtd
Avg
Est
Max
lb
ai/

acre/
y
r
#
appl
/
yr
lb
ai/

A/
appl
(%
of
total
lb
ai
used
on
this
site)

50
Grapefruit
195
0
0
0.0
0.0
0
0
0.7
1.6
0.5
FL
100%

Grapes
915
80
132
8.7
14.4
310
490
3.9
1.9
2.1
NY
CA
MI
OH
80%

Hay,
Other
32,427
0
0
0.0
0.0
0
0
1.5
2.0
0.8
MI
100%

Lemons
64
0
0
0.1
0.1
0
0
0.9
1.6
0.6
FL
100%

Lettuce
272
5
18
1.8
6.6
17
68
3.4
2.4
1.4
AZ
CA
90%

Lots/
Farmsteads/
etc
25,820
1
2
0.0
0.0
1
3
0.8
1.8
0.4
AR
FL
MA
CA
80%

Melons,
Honeydew
32
3
4
8.2
13.2
6
10
2.2
2.5
0.9
TX
100%

Onions
161
62
124
38.5
77.0
260
510
4.2
1.0
4.2
NY
OR
GA
CA
TX
80%

Oranges
867
2
5
0.2
0.6
9
18
4.5
1.9
2.4
FL
100%

Peaches
228
2
7
0.9
3.2
8
29
3.9
3.1
1.2
MA
IL
NY
90%

Peanuts
1,625
15
37
0.9
2.3
27
89
1.8
1.6
1.2
TX
OK
NC
80%

Pears
81
26
41
32.1
50.6
180
290
6.9
2.1
3.2
CA
WA
OR
80%

Pecans
492
0
0
0.0
0.1
1
1
3.6
5.5
0.7
AL
90%

Peppers,
Bell
61
3
8
4.9
13.1
25
91
8.3
7.0
1.2
FL
90%

Plums
&
Prunes
140
0
1
0.3
0.6
1
3
2.0
1.9
1.0
ME
PA
CA
86%

Potatoes
1,411
510
705
36.1
50.0
1,970
2,285
3.9
3.7
1.0
ID
WA
ME
MN
ND
WI
54%
Site
Acres
Grown
(
000)
Acres
Treated
(
000)
%
of
Crop
Treated
LB
AI
Applied
(
000)
Average
Application
Rate
States
of
Most
Usage
Wtd
Avg
Est
Max
Wtd
Avg
Est
Max
Wtd
Avg
Est
Max
lb
ai/

acre/
y
r
#
appl
/
yr
lb
ai/

A/
appl
(%
of
total
lb
ai
used
on
this
site)

51
Pumpkins
38
1
4
3.5
11.3
2
7
1.6
2.0
0.8
MI
100%

Rice
2,930
0
1
0.0
0.0
1
1
1.7
1.0
1.7
MS
TX
90%

Soybeans
61,380
14
27
0.0
0.0
8
17
0.6
1.1
0.5
IA
OH
MN
90%

Squash
56
23
48
41.1
85.7
210
490
9.1
1.0
9.1
FL
GA
MI
80%

Sugar
Beets
1,427
19
42
1.3
2.9
42
124
2.2
1.6
1.4
ND
MN
95%

Sunflower
2,756
1
1
0.0
0.0
1
3
2.8
1.0
2.8
ND
100%

Sweet
Corn,
Fresh
189
35
51
18.5
27.0
210
308
6.0
5.1
1.2
FL
94%

Sweet
Corn,
Proc.
475
58
105
12.2
22.1
130
250
2.2
2.3
1.0
MN
WI
IL100%

Tobacco
695
9
19
1.3
2.7
15
41
1.7
1.5
1.1
KY
TN
80%

Tomatoes,
Fresh
121
59
97
48.8
80.2
860
1,790
14.6
10.5
1.4
FL
94%

Tomatoes,
Proc.
324
39
73
12.0
22.5
110
220
2.8
2.1
1.4
CA
85%

Walnuts
208
1
4
0.6
1.9
5
14
3.9
2.5
1.6
CA
100%

Watermelons
327
92
105
28.1
32.1
310
590
3.4
1.0
3.4
FL
TX
GA
80%

Wheat,
Spring
20,857
194
470
0.9
2.3
160
380
0.8
1.2
0.7
ND
MN
80%

Wheat,
Winter
43,282
65
187
0.2
0.4
76
198
1.2
1.1
1.1
OK
NE
MS
SC
KY
60%

Woodland
62,950
2
6
0.0
0.0
4
14
2.1
2.2
1.0
FL
OR
PA
MI
95%
Site
Acres
Grown
(
000)
Acres
Treated
(
000)
%
of
Crop
Treated
LB
AI
Applied
(
000)
Average
Application
Rate
States
of
Most
Usage
Wtd
Avg
Est
Max
Wtd
Avg
Est
Max
Wtd
Avg
Est
Max
lb
ai/

acre/
y
r
#
appl
/
yr
lb
ai/

A/
appl
(%
of
total
lb
ai
used
on
this
site)

52
1,612
2,274
6,307
8,854
COLUMN
HEADINGS
Wtd
Avg
=
Weighted
average­­
the
most
recent
years
and
more
reliable
data
are
weighted
more
heavily.

Est
Max
=
Estimated
maximum,
which
is
estimated
from
available
data.

Average
application
rates
are
calculated
from
the
weighted
averages.

NOTES
ON
TABLE
DATA
Usage
data
primarily
covers
1992
­
2001
Calculations
of
the
above
numbers
may
not
appear
to
agree
because
they
are
displayed
as
rounded
to
the
nearest
1000
for
acres
treated
or
lb.
a.
i.
(
Therefore
0
=
<
500)

to
one
decimal
percentage
points
for
%
of
crop
treated.

SOURCES:
EPA
data,
USDA,
and
National
Center
for
Food
and
Agricultural
Policy.