1
Notice
of
Filing
Interregional
Research
Protect
#
4
(
IR­
4)

3E4173,
5E4570,
9E5054,
and
9E5061
EPA
has
received
pesticide
petitions
3E4173,
5E4570,
9E5054,
and
9E5061
from
IR­
4,
681
Highway
1
South,
North
Brunswick,
NJ
08902­
3390
proposing,
pursuant
to
section
408(
d)
of
the
Federal
Food,
Drug,
and
Cosmetic
Act
(
FFDCA),
21
U.
S.
C.
346a(
d),
to
amend
40
CFR
part
180.176
by
establishing
tolerances
for
residues
of
mancozeb
in
or
on
the
raw
agricultural
commodities
sugar
apple,
cherimoya,
atemoya,
custard
apple,
and
sweetsop
at
3
ppm
(
9E5061);
mango,
star
apple
(
caimito),
canistel,
mamey
sapote,
sapodilla,
and
white
sapote
at
15
ppm
(
5E4570);
ginseng
at
2
ppm
(
9E5054);
and
the
cucurbit
vegetable
group
at
4
ppm
(
3E4173).
EPA
has
determined
that
the
petitions
contain
data
or
information
regarding
the
elements
set
forth
in
section
408(
d)(
2)
of
the
FFDCA;
however,
EPA
has
not
fully
evaluated
the
sufficiency
of
the
submitted
data
at
this
time
or
whether
the
data
support
granting
of
the
petitions.
Additional
data
may
be
needed
before
EPA
rules
on
the
petitions.

A.
Residue
Chemistry
1.
Plant
metabolism.
The
plant
metabolism
of
mancozeb
is
understood.
Plant
metabolism
has
been
evaluated
in
five
diverse
crops,
including
potato,
soybean,
sugar
beet,
tomato,
and
wheat.
These
studies
demonstrate
that
mancozeb
is
extensively
metabolized
to
natural
products
(
proteins,
carbohydrates,
lipids,
lignins,
etc.)
with
minor
amounts
of
degradation
products
including
ethylenethiourea
(
ETU),
ethyleneurea,
ethylene
bisisocyanate
sulfide,
and
ethylenediamine.

2.
Analytical
method.
Residues
of
mancozeb
are
determined
by
decomposing
the
residue
with
a
strong
acid
to
release
carbon
disulfide
(
CS
2
).
The
CS
2
can
be
measured
by
gas
chromatography
or
by
absorbance
of
a
colored
copper
dithiocarbamate
complex
formed
by
sweeping
the
CS
2
through
a
trap
and
into
a
reaction
tube
containing
a
solution
of
copper
acetate
and
an
amine.
Adequate
methodology
for
enforcement
is
available
in
the
Pesticide
Analytical
Manual
(
PAM
II,
Method
II).

3.
Magnitude
of
Residues.
The
residues
of
mancozeb
will
not
exceed
3
ppm
in
or
on
sugar
apple,
cherimoya,
atemoya,
custard
apple,
and
sweetsop;
15
ppm
in
or
on
mango,
star
apple
(
caimito),
canistel,
mamey
sapote,
sapodilla,
and
white
sapote;
2
ppm
in
or
on
ginseng;
or
4
ppm
in
or
on
the
cucurbit
crop
group.

B.
Toxicological
Profile
2
1.
Acute
toxicity.
Mancozeb
is
not
acutely
toxic,
with
Category
IV
toxicity
for
the
oral,
dermal,
and
inhalation
routes.
Mancozeb
is
not
a
skin
irritant
(
Category
IV)
and
it
is
not
a
skin
sensitizer.
Mancozeb
is
classified
as
Category
III
for
eye
irritation.

2.
Genotoxicity.
Mancozeb
was
negative
(
non­
mutagenic)
in
an
Ames
assay
with
and
without
activation.
It
was
negative
in
a
hypoxanthine
guanine
phosphoribosyl
transferase
(
HGPRT)
gene
mutation
assay
using
Chinese
hamster
ovary
(
CHO)
cells
when
tested
with
and
without
activation.
It
was
negative
in
the
mouse
host­
mediated
assay.
Mancozeb
was
negative
in
the
in
vivo
bone
marrow
cytogenetic
study
and
mouse
micronucleus
assay.
Mancozeb
did
not
induce
unscheduled
DNA
synthesis
(
UDS)
or
repair,
it
was
negative
in
the
in
vitro
transformation
(
10T1/
2
cell)
and
in
vitro
transformation/
promotion
(
10T1/
2
cell)
studies.
In
the
sister
chromatid
exchange
(
SCE)
assay
with
CHO
cells,
mancozeb
was
positive
without
activation
and
negative
with
activation.
A
weight
of
the
evidence
evaluation
demonstrates
that
mancozeb
is
not
genotoxic
in
mammalian
systems.

3.
Reproductive
and
developmental
toxicity. 
i.
Developmental
toxicity
in
the
rat.
In
the
developmental
study
in
rats,
the
maternal
(
systemic)
no
observed
adverse
effect
level
(
NOAEL)
was
32
mg/
kg/
day,
with
a
maternal
lowest
observed
effect
level
(
LOAEL)
of
128
mg/
kg/
day
based
on
decreased
food
consumption,
body
weight,
and
body
weight
gains.
The
developmental
NOAEL
was
128
mg/
kg/
day
and
the
developmental
LOAEL
was
512
mg/
kg/
day
based
on
gross
developmental
effects,
central
nervous
and
skeletal
effects,
cryptorchidism,
abortions,
increased
resorptions
and
decreased
fetal
weight.
These
effects
occurred
only
at
doses
that
produced
significant
maternal
toxicity,
including
mortality,
and
are
not
considered
relevant
for
human
risk
assessment.
_
There
were
no
developmental
effects
at
doses
below
those
which
were
maternally
toxic,
so
mancozeb
was
not
uniquely
toxic
to
the
conceptus.

ii.
Developmental
toxicity
in
the
rabbit.
In
the
developmental
study
in
rabbits,
the
maternal
(
systemic)
NOAEL
was
30
mg/
kg/
day
and
the
maternal
LOAEL
was
80
mg/
kg/
day
based
on
reduced
feed
intake,
weight
loss,
mortality,
and
clinical
signs.
The
developmental
NOAEL
was
greater
than
80
mg/
kg/
day
because
no
effects
were
seen
without
severe
maternal
toxicity.
Mancozeb
was
not
developmentally
toxic
in
this
study.

iii.
Reproductive
toxicity.
In
the
2­
generation
reproduction
study
in
rats,
the
maternal
(
systemic)
NOAEL
was
6.95/
7.47
mg/
kg/
day
males/
females
and
the
parental
LOAEL
was
68.90/
79.37
mg/
kg/
day
males/
females
based
on
body
weight
decrements,
increased
relative
thyroid
weights,
and
increased
incidence
of
thyroid
follicular
cell
hyperplasia.
The
reproductive
NOAEL
is
greater
than
or
equal
to
69.90/
79.37
mg/
kg/
day
males/
females
(
the
highest
dose
tested).
There
were
no
adverse
reproductive
or
offspring
effects.
Mancozeb
does
not
show
reproductive
toxicity.
In
conclusion,
mancozeb
is
not
a
reproductive
toxicant
and
developmental
effects
occurred
only
at
doses
that
were
3
maternally
toxic
and
the
effects
are
secondary
to
excessive
maternal
toxicity.
4.
Subchronic
toxicity.
 
i.
Rat
90­
day
feeding
study.
A
subchronic
feeding
study
in
rats
conducted
for
13
weeks
had
a
NOAEL
of
9.24/
14.98
mg/
kg/
day
in
females/
males
and
a
LOAEL
of
17.82/
57.34
mg/
kg/
day
in
females/
males
based
on
decreased
serum
thyroxine.
In
males,
the
LOAEL
was
57.34
mg/
kg/
day
based
on
decreased
body
weights,
changes
in
thyroid
hormones,
changes
in
liver
enzymes,
increased
absolute
and
relative
thyroid
weights
and
increased
relative
liver
weights
in
the
males.

ii.
Mouse
90­
day
feeding
study.
A
90­
day
subchronic
study
resulted
in
a
NOAEL
of
18.13/
21.68
mg/
kg/
day
in
males/
females
and
a
LOAEL
of
166.9/
233.8
mg/
kg/
day
in
males/
females
based
on
microscopic
lesions
of
thyroid
follicular
cell
hypertrophy
or
hyperplasia
in
females
and
decreased
liver
MFO
enzyme
activity
in
males.

iii.
Dog
90­
day
feeding
study.
A
subchronic
feeding
study
in
dogs
conducted
for
three
months
had
a
NOAEL
of
2.98/
3.35
mg/
kg/
day
in
males/
females
and
a
LOAEL
of
28.62/
28.91
mg/
kg/
day
in
males/
females
based
on
dehydration,
decreased
body
weights
and
food
consumption,
anemia,
thymic
cortical
lymphoid
depletion,
elevated
cholesterol
and
prostate
hypogenesis.

iv.
Rat
28­
day
dermal
study.
No
toxicity,
including
no
changes
in
thyroid
hormones,
was
seen
at
the
limit
dose
of
1000
mg/
kg/
day.
The
NOAEL
is
greater
than
1000
mg/
kg/
day.

v.
Rat
90
day
neuropathology
study.
A
subchronic
feeding
study
in
rats
conducted
for
three
months
had
a
NOAEL
of
8.2
mg/
kg/
10.5
mg/
kg
in
males/
females
based
on
decreased
body
weight,
body
weight
gain
and
food
consumption
in
females
and
neurohistopathological
changes
in
both
sexes
at
49.7/
63.3
mg/
kg
in
males/
females.

5.
Chronic
toxicity. 
i.
Rat.
A
24­
month
chronic/
carcinogenicity
study
in
male
and
female
rats
was
conducted
at
20,
60,
125,
or
750
ppm
of
mancozeb.
The
NOAEL
was
125
ppm
(
4.83/
6.72
mg/
kg/
day
in
males/
females)
with
a
LOAEL
of
750
ppm
(
30.9/
40.2
mg/
kg/
day
in
males/
females)
based
on
changes
in
thyroid
hormone
levels,
microscopic
thyroid
changes
(
follicular
cell
hypertrophy
and
hyperplasia,
adenomas
and
carcinomas),
changes
in
thyroid
weights
and
bilateral
retinopathy.

ii.
Mouse.
A
78­
week
chronic/
oncogenicity
study
was
conducted
in
male
and
female
mice
dosed
at
0,
30,
100,
or
1000
ppm.
The
NOAEL
was
100
ppm
(
13/
18
mg/
kg/
day
in
males/
females)
based
on
minor
decreased
body
weight
and
body­
weight
gain
and
changes
in
hormone
levels
at
the
LOAEL
of
1000
ppm
(
131/
180
mg/
kg/
day
in
males/
females).
There
was
no
evidence
of
carcinogenicity.

iii.
Dog.
A
1­
year
feeding
study
in
dogs
resulted
in
a
NOAEL
of
50
ppm
(
1.75
mg/
kg/
day)
for
males
and
200
ppm
(
7.02
mg/
kg/
day)
for
females.
The
LOAEL
was
200
4
ppm
(
7.26
mg/
kg/
day)
in
males
based
on
decreased
body
weight
gain
and
800
ppm
(
29.24
mg/
kg/
day)
in
females
based
on
anemia.

iv.
Carcinogenicity.
Mancozeb
is
classified
as
a
Group
B2
carcinogen
based
on
the
metabolite
ETU.
ETU
has
a
Q*
of
0.06
(
mg/
kg/
day)­
1
based
on
mouse
liver
tumors
and
a
¾
scaling
factor.

6.
Animal
metabolism.
The
absorption,
distribution,
excretion,
and
metabolism
of
mancozeb
in
rats,
goats,
and
hens
were
investigated.
Following
oral
administration,
mancozeb
was
rapidly
and
essentially
completely
excreted.
The
bulk
of
the
residue
is
incorporated
into
natural
products.

7.
Metabolite
toxicity.
The
mancozeb
metabolite
of
toxicological
concern
is
ethylenethiourea
(
ETU).
ETU
is
classified
as
a
B2
carcinogen
with
a
Q*
of
0.06
(
mg/
kg/
day)­
1
based
on
mouse
liver
tumors
and
¾
scaling
factor.
The
non­
cancer
chronic
toxicity
of
ETU
is
based
on
a
NOAEL
of
0.18
mg/
kg/
day
in
a
chronic
dog
study.
Using
a
1000X
safety
factor
(
100X
based
on
inter­
and
intra­
species
uncertainty
and
10X
database
uncertainty
factor),
the
cPAD
is
0.0002
mg/
kg/
day.
The
acute
endpoint
is
based
on
a
rat
developmental
study
with
a
NOAEL
of
5
mg/
kg/
day,
resulting
in
an
aPAD
of
0.005
mg/
kg/
day
with
a
1000X
safety
factor.
The
ETU
developmental
effects
are
species­
specific.
ETU
is
not
developmentally
toxic
in
rabbits,
guinea
pigs
or
cats
and
has
equivocal
effects
in
mice
and
hamsters.

8.
Endocrine
disruption.
The
endocrine
system
includes
the
reproductive
hormones
estrogen
and
androgens
as
well
as
the
thyroid
hormone
system.
Mancozeb
and
ETU
are
not
known
to
interfere
with
reproductive
hormones
and
mancozeb
and
ETU
do
not
have
reproductive
toxicity.
While
thyroid
effects
were
seen
in
testing
in
rodents,
it
is
well
known
and
accepted
that
rats
are
more
sensitive
to
thyroid
effects
than
humans.
Mancozeb
and
ETU
are
not
expected
to
show
thyroid
effects
at
the
levels
of
human
or
environmental
exposure.
Additionally,
the
chronic
risk
assessments
are
based
on
thyroid
effects
and
the
%
cPAD
is
substantially
below
the
level
of
concern.

C.
Aggregate
Exposure
1.
Dietary
exposure. 
i.
Food.
Dietary
exposure
assessments
for
mancozeb
and
ETU
from
mancozeb
were
conducted
using
the
Dietary
Exposure
Evaluation
Model
(
DEEM)
software
with
the
Food
Commodity
Intake
Database
(
DEEM­
FCID
 
,
Version
1.3),
which
incorporates
consumption
data
from
USDA's
Continuing
Survey
of
Food
Intakes
by
Individuals
(
CSFII),
1994­
1996
and
1998.
The
acute
and
chronic
dietary
(
food)
risk
analyses
utilized
anticipated
residue
values
from
a
market
basket
survey
for
EBDCs
and
ETU
and
field
trial
data
when
market
basket
survey
data
were
not
available.
For
the
crops
described
in
these
petitions,
papaya
field
trial
data
with
mancozeb
applied
at
the
maximum
papaya
label
rate
were
used
as
a
surrogate
for
mango,
star
apple
(
caimito),
5
canistel,
mamey
sapote,
sapodilla,
and
white
sapote.
Maximum
rate
sugar
apple
field
trial
data
were
used
for
sugar
apple,
cherimoya,
atemoya,
custard
apple,
and
sweetsop.
Field
trial
data
were
used
for
ginseng.
Cucumber,
squash,
and
melon
field
trial
data
were
used
to
support
the
cucurbit
crop
group,
with
the
exception
that
cucumber
market
basket
survey
data
were
used
for
cucumbers.
The
exposure
and
risk
assessments
described
in
this
Notice
of
Filing
include
all
crops
currently
on
the
mancozeb
labels
plus
the
above­
mentioned
crops
in
the
four
petitions.
Residues
were
adjusted
for
processing
factors,
cooking
factors,
and
percent
of
crop
treated.
However,
a
default
of
100%
crop
treated
was
assumed
for
the
crops
in
the
four
petitions
that
are
the
subject
of
this
Notice.
For
the
purposes
of
this
Notice
of
Filing,
exposures
calculated
by
EPA
have
been
used
to
describe
the
acute
and
chronic
risk
assessments.
Numerous
refinements
can
be
made
with
actual
percent
of
crop
treated
data
for
some
crops
and
corrections
to
anticipated
residue
calculations.
These
adjustments
will
lead
to
considerable
reduction
of
the
acute
and
chronic
exposures.
The
adjustments
have
been
taken
into
account
for
the
theoretical
cancer
risk
assessments.

a.
Acute
dietary
exposure.
There
is
no
acute
toxicology
endpoint
for
mancozeb
because
mancozeb
is
not
developmentally
toxic.
The
exposure
from
ETU
derived
from
mancozeb
at
the
99.9th
percentile
is
0.000898
mg/
kg/
day,
or
18%
of
the
aPAD
of
0.005
mg/
kg/
day.
Mancozeb
is
a
member
of
the
ethylenebisdithiocarbamate
(
EBDC)
group
of
fungicides.
The
EBDC
group
also
includes
maneb
and
metiram.
The
ETUdietary
exposure
from
all
sources
(
including
mancozeb,
maneb,
and
metiram)
is
0.0026
mg/
kg/
day,
or
52%
aPAD.
The
%
aPAD
will
be
lower
when
corrections
to
EPA's
calculations
are
taken
into
account.

b.
Chronic
dietary
exposure.
The
chronic
reference
dose
for
mancozeb
is
based
on
a
NOAEL
of
4.83
mg/
kg/
day
and
an
uncertainty
factor
of
100,
resulting
in
a
cPAD
of
0.05
mg/
kg/
day.
The
cPAD
for
ETU
is
0.0002
mg/
kg/
day
based
on
a
NOAEL
of
0.18
mg/
kg/
day
and
an
uncertainty
factor
of
1000,
which
includes
an
extra
10X
database
uncertainty
factor.
The
mancozeb
chronic
(
non­
cancer)
dietary
exposure
to
the
general
U.
S.
population
is
0.000053
mg/
kg/
day,
or
<
1%
cPAD;
and
is
0.000175
mg/
kg/
day,
or
<
1%
cPAD
for
children
1­
2
years
old,
which
are
the
most
highly
exposed
population
subgroup.
For
ETU
derived
from
mancozeb,
the
exposures
are
0.000022
or
0.000065
mg/
kg/
day,
resulting
in
11%
cPAD
for
the
general
U.
S.
population
or
33%
cPAD
for
children
1­
2
years
old,
respectively.
The
ETU
exposure
from
all
sources
is
0.000034
mg/
kg/
day
or
17%
cPAD
for
the
general
U.
S.
population
and
0.000104
mg/
kg/
day,
or
52%
cPAD
for
children
1­
2
years
old.

c.
Cancer
dietary
exposure.
The
cancer
dietary
exposure
is
based
on
ETU,
with
a
Q*
of
0.06
(
mg/
kg/
day)­
1.
The
ETU
exposure
comes
from
three
sources:
directly
measured
ETU,
metabolic
ETU
from
7.5%
conversion
of
an
EBDC
to
ETU
in
vivo,
and
processing
ETU,
due
to
formation
of
some
ETU
when
an
EBDC
is
heated.
The
relevant
6
population
is
the
general
U.
S.
population.
The
theoretical
cancer
risk
for
ETU
derived
from
mancozeb
is
6.5
X
10­
7.
The
theoretical
cancer
risk
estimate
of
ETU
from
all
sources
is
1.2
X
10­
6.

ii.
Drinking
water.
The
drinking
water
risk
is
based
only
on
ETU
because
mancozeb
is
very
short­
lived
in
soil
and
water
and
is
not
expected
to
reach
drinking
water
for
human
consumption
from
either
surface
water
or
ground
sources.
Monitoring
data
for
ETU
from
a
targeted
surface
water
and
ground
water
study
are
available
for
risk
assessment.
Samples
were
collected
from
rural
wells
and
community
water
systems
in
areas
of
high
usage
of
EBDC
fungicides.
In
the
study,
none
of
the
samples
from
surface
water
monitoring
sites
had
residues
that
were
above
the
limit
of
quantitation
of
0.1
ppb.
For
surface
water,
the
estimated
drinking
water
concentrations
(
EDWC's)
for
acute
exposure
range
from
0.1
ppb
from
the
monitoring
study
to
25.2
ppb
based
on
PRZM­
EXAMS
modeling.
PRZM­
EXAMS
modeling
was
based
on
application
of
maneb
to
peppers
in
Florida
at
the
maximum
label
rate
of
6
applications
of
2.4
lb
a.
i./
acre,
an
ETU
aerobic
soil
half­
life
of
about
3
days,
aquatic
aerobic
metabolism
half­
life
assumed
to
be
6
days
(
double
the
soil
half­
life),
and
an
aerobic
aquatic
metabolism
half­
life
of
149
days.
The
modeling
prediction
can
be
refined
by
incorporating
the
average
actual
application
rate
instead
of
the
maximum
label
application
rate.
When
the
actual
application
rate
of
1.18
lb
a.
i./
acre
is
used
for
the
modeling,
the
highest
one­
in
ten
year
acute
surface
water
EDWC
is
7.6
ppb
rather
than
25.2
ppb.
The
surface
water
estimates
will
be
considerably
reduced
by
incorporating
the
refined
EDWC.
The
chronic
surface
water
EDWC
is
calculated
conservatively
at
the
limit
of
quantitation
of
0.1
ppb
based
on
the
monitoring
data.

A
ground
water
EDWC
for
all
durations
(
acute
and
chronic)
of
0.21
ppb
is
based
on
a
result
from
the
targeted
monitoring
study
in
Florida.
The
0.21
ppb
is
the
highest
concentration
in
an
untreated
sample
at
a
community
water
system
intake
source.
The
0.21
ppb
is
a
conservative
value
for
risk
assessment
because
ETU
was
not
detected
in
any
of
the
treated
community
drinking
water
in
any
of
the
84
sites
in
the
monitoring
survey.
The
concentration
for
human
consumption
is
actually
<
0.1
ppb
based
on
the
analysis
of
the
treated
water
samples.

Potential
exposure
to
ETU
from
both
ground
and
surface
water
is
below
the
drinking
water
level
of
concern
(
DWLOC)
for
acute
risk
when
combined
with
exposure
through
food.
For
mancozeb
uses,
the
acute
DWLOC
for
ETU
from
mancozeb
is
123
ug/
L.
EPA's
calculated
upper­
bound
ETU
estimates
of
25.2
ppb
modeled
for
surface
water
and
0.21
ppb
in
the
ground
water
monitoring
study
are
significantly
less
than
the
DWLOC.
Using
actual
application
rates
of
1.18
lb
a.
i./
acre,
the
acute
EDWC
of
7.6
ppb
is
even
lower
than
the
DWLOC.

With
a
surface
water
EDWC
of
0.1
ppb,
the
surface
water
chronic
risk
has
a
%
cPAD
of
1.1%
for
the
U.
S.
population
and
1.6%
for
children
1­
2
years.
The
theoretical
7
surface
water
cancer
risk
is
1.27
X
10­
7.
With
an
EDWC
of
0.21
ppb
to
calculate
the
chronic
and
cancer
risks
for
ground
water,
the
%
cPAD
is
2.2%
for
the
U.
S.
population
and
3.3%
for
children
1­
2
years
old
and
the
theoretical
ground
water
cancer
risk
is
2.66
X
10­
7.
The
aggregate
food
and
surface
water
exposure
for
ETU
from
mancozeb
yields
an
ETU
DWLOC
of
123
ppb,
and
the
modeled
EDWC
of
25.2
ppb
is
below
the
level
of
concern.
The
acute
food
and
surface
water
aggregate
risk
for
ETU
from
all
sources
is
86%
of
the
aPAD.
The
acute
risks
will
be
lower
with
incorporation
of
7.6
ppb
surface
water
EDWC
based
on
actual
use
patterns.
For
aggregate
risk
of
food
and
water
from
surface
water
and
ground
water
sources,
EPA
calculated
chronic
risks
for
ETU
from
mancozeb
of
12%
and
13%
cPAD,
respectively,
and
34%
and
36%,
respectively,
for
children
1­
2
years
old.
When
Mancozeb
Task
Force
corrections
are
incorporated,
the
aggregate
food
and
cancer
risk
for
mancozeb­
derived
ETU
in
food
and
water
is
9
X
10­
7
and
1.0
X
10­
6
from
surface
water
and
ground
water
sources,
respectively.
The
results
of
the
acute,
chronic,
and
cancer
risk
assessments
demonstrate
that
exposure
to
ETU
from
mancozeb
and
other
EBDC
sources
would
not
result
in
unacceptable
levels
of
aggregate
human
health
risk.

2.
Non­
dietary
exposure. 
i.
Residential
uses.
Mancozeb
is
used
on
sod
farms
and
by
home
gardeners.
The
sod
MOE
is
greater
than
the
target
ETU
MOE
of
1000
for
exposure
to
infants
and
children
when
there
is
a
3
day
pre­
harvest
restriction
for
mancozeb
applications
to
sod.
This
value
is
very
conservative
because
it
does
not
take
into
account
all
of
the
watering
that
occurs
on
sod
after
it
is
transplanted
to
ensure
that
the
sod
knits
to
the
ground,
and
does
not
take
into
account
the
fact
that
children
are
not
likely
to
be
on
transplanted
sod
before
it
is
established.
EPA
calculated
risks
to
home
gardeners
applying
mancozeb
to
vegetable
gardens
and
ornamentals,
using
the
maximum
application
rate
of
2.4
lb
a.
i./
acre
for
all
crops.
For
handlers,
short
term
margins
of
exposure
(
MOEs)
are
significantly
higher
than
the
target
MOEs
of
100
and
1000
for
mancozeb
and
ETU,
respectively.
Mancozeb
MOEs
range
from
890,000
to
3,000,000
and
ETU
MOEs
range
from
110,000
to
620,000.
The
ETU
cancer
risks
range
from
2
X
10­
8
to
4
X
10­
9.
The
highest
adult
cancer
post­
application
risk
is
5.3
X
10­
7
for
homeowners
harvesting
sweet
corn.
This
risk
is
highly
conservative
because
the
risk
assessment
was
conducted
at
double
the
label
rate
for
sweet
corn
and
there
is
minimal
use
of
mancozeb
on
home
garden
sweet
corn.

ii.
Recreational
uses.
Mancozeb
is
used
on
golf
courses
and
athletic
fields.
Using
100%
of
the
golf
courses
treated,
the
MOE
to
adult
golfers
is
6,600
and
the
theoretical
cancer
risk
is
2.0
X
10­
7.
However,
only
1.6%
of
the
golf
courses
are
treated
with
mancozeb,
and
with
this
refinement
the
theoretical
cancer
risk
is
3.2
X
10­
9.
EPA
calculated
an
athlete
MOE
of
450,
however
this
calculation
does
not
account
for
the
clothing
worn
by
athletes.
The
cancer
risk
to
athletes
was
calculated
to
be
6.0
X
10­
7
with
100%
of
the
athletic
fields
treated.
However,
the
mancozeb
use
on
athletic
fields
is
so
low
8
that
its
usage
is
not
even
reported.
Using
a
conservative
estimate
of
1%
of
the
athletic
fields
treated,
the
theoretical
athletic
cancer
risk
is
6
X
10­
9.

The
aggregate
risk
for
ETU
from
mancozeb
ranges
from
6.8
X
10­
7
to
a
maximum
of
1.3
X
10­
6,
even
with
the
double
application
rate
on
home
garden
sweet
corn.
The
aggregate
risk
from
all
sources
of
ETU
ranges
from
1.4
X
10­
6
to
2.0
X
10­
6.

D.
Cumulative
Effects.
Mancozeb
is
a
member
of
the
EBDC
class
of
fungicides,
all
of
which
have
ETU
as
a
common
metabolite.
During
a
previous
Special
Review
of
the
EBDCs
(
mancozeb,
maneb,
and
metiram),
the
Agency
considered
the
three
active
ingredients
to
be
related
due
to
the
common
metabolite
ETU.
For
the
purposes
of
this
Notice,
both
the
ETU
derived
from
mancozeb
and
ETU
from
all
EBDCs
have
been
considered.

E.
Safety
Determination.

1.
U.
S.
population.
EPA
has
assigned
an
uncertainty
factor
of
100
for
mancozeb
and
1000
for
ETU
for
toxicology
endpoints
with
threshold
effects.
The
100
fold
safety
factor
includes
intraspecies
and
interspecies
variations.
For
ETU,
an
extra
10X
uncertainty
factor
was
added
to
account
for
database
uncertainties.
EPA
determined
that
no
additional
Special
FQPA
safety
factors
are
required.
The
uncertainty
factors
have
been
applied
to
the
acute
and
chronic
threshold
risk
assessments.
For
the
acute
risk
assessment,
the
subpopulation
of
concern
is
females
13­
49.
EPA
determined
that
the
aggregate
(
food
and
drinking
water)
acute
risk
to
ETU
from
all
sources
is
86%
of
the
aPAD
and
the
DWLOC
for
ETU
derived
from
mancozeb
is
123,
exceeding
the
surface
water
EDWC
of
25.2
ppb,
which
can
be
refined
to
7.6
ppb
for
future
risk
assessments.
Because
the
acute
aggregate
risks
are
less
than
100%
of
the
aPAD
they
are
below
the
level
of
concern.
An
acute
endpoint
for
mancozeb
is
not
appropriate
because
mancozeb
is
not
developmentally
toxic.
The
chronic
risks
for
mancozeb
in
food
are
<
1%
for
the
U.
S.
population.
The
aggregate
food
and
water
risk
for
ETU
derived
from
mancozeb
is
12%
cPAD
for
surface
water
and
13%
for
ground
water.
EPA
calculated
aggregate
food
and
water
risks
for
ETU
from
all
sources
of
18%
for
surface
water
and
19%
for
ground
water.
These
risks
are
less
than
100%
of
the
cPAD
and
are
therefore
below
the
level
of
concern.
The
acute
and
chronic
risks
include
conservative
assumptions
and
will
be
reduced
with
incorporation
of
adjustments
and
corrections
provided
by
the
registrants.

Aggregate
mancozeb
MOEs
for
residential
handlers
(
chronic
food
plus
residential)
range
from
140,000
to
160,000.
The
ETU
short­
term
aggregate
risk
for
residential
handlers
applying
mancozeb
is
below
EPA's
level
of
concern,
with
aggregate
MOE's
ranging
from
75,000
to
161,000
(
food,
water,
and
residential
exposure).
Aggregate
MOEs
from
all
sources
of
ETU
for
chronic
food
and
drinking
water
and
golfing
or
gardening
exposures
range
from
4,500
to
62,000.
These
MOEs
are
higher
than
the
target
9
of
100
and
are
not
of
concern.

Theoretical
cancer
aggregate
risks
were
calculated
for
food
and
water,
food/
water/
golfing,
food/
water/
home
garden
handler,
food/
water/
home
garden
post
application,
and
food/
water/
athletic
exposures,
with
either
surface
water
or
ground
water.
The
aggregate
theoretical
cancer
risk
for
ETU
derived
from
mancozeb
ranges
from
6.8
X
10­
7
to
a
maximum
of
1.3
X
10­
6.
The
theoretical
risk
from
ETU
from
all
sources
ranges
from
1.4
X
10­
6
to
2.0
X
10­
6.
These
risks
are
not
statistically
different
from
1
X
10­
6
and
are
thus
below
the
level
of
concern.

2.
Infants
and
children.
EPA
evaluated
the
potential
for
increased
susceptibility
of
infants
and
children
from
exposure
to
mancozeb.
Acceptable
developmental
and
reproduction
studies
demonstrated
that
there
was
no
indication
of
increased
susceptibility
to
fetuses
or
offspring
in
the
developmental
and
reproduction
studies.
Based
on
the
lack
of
evidence
of
pre­
and/
or
postnatal
susceptibility
resulting
from
exposure
to
mancozeb
and
considering
the
lack
of
residual
uncertainties,
the
Special
FQPA
Safety
Factor
was
removed
(
reduced
to
1X).
The
Agency
also
determined
that
there
was
no
need
for
a
database
uncertainty
factor
for
mancozeb.
EPA
also
evaluated
the
potential
for
increased
susceptibility
of
infants
and
children
from
exposure
to
ETU.
While
ETU
had
developmental
effects
in
rats,
the
effects
are
well
characterized
and
there
is
a
clear
dose
response
relationship
with
a
well­
established
NOAEL
based
on
numerous
studies
in
rats.
The
developmental
NOAEL
with
the
lowest
endpoint
was
selected
for
the
acute
reference
dose.
Additionally,
the
thyroid
effects
from
ETU
were
selected
for
deriving
the
chronic
reference
dose.
Therefore,
EPA
concluded
that
there
were
no
residual
uncertainties
with
regard
to
pre­
and/
or
postnatal
toxicity
and
that
the
Special
FQPA
Safety
Factor
could
be
removed
(
reduced
to
1X).
EPA
concluded
that
a
10X
database
uncertainty
factor
was
required
for
ETU,
so
the
total
ETU
safety
factor
is
1000X.

For
chronic
risk,
the
most
highly
exposed
population
is
children
1­
2
years
old.
The
%
cPAD
for
mancozeb
is
<
1%
and
the
%
cPAD
for
ETU
is
33%.
The
%
cPAD
for
ETU
from
all
sources
is
52%.
These
numbers
are
less
than
100%
and
are
therefore
below
the
level
of
concern.
The
risk
to
infants
and
children
from
transplanted
sod
was
also
evaluated.
With
a
three
day
pre­
harvest
restriction
interval,
the
target
MOE
of
1000
is
met.
This
number
is
highly
conservative
because
it
does
not
account
for
the
extensive
watering
of
sod
after
transplant
or
the
length
of
time
that
occurs
prior
to
sod
exposure
to
enable
the
sod
to
get
established.

F.
International
Tolerances.
Of
the
crops
in
this
petition,
Codex
tolerances
have
been
established
for
cucumber
(
2
ppm
carbon
disulfide
equivalents,
or
4
ppm
mancozeb),
mango
(
2
ppm
carbon
disulfide
equivalents,
or
4
ppm
mancozeb),
summer
squash
(
1
ppm
carbon
disulfide,
or
2
ppm
mancozeb),
and
winter
squash
(
0.1
ppm
carbon
disulfide,
or
0.2
ppm
mancozeb).
Numerous
additional
Codex
tolerances
are
established
for
other
10
commodities.
Because
the
use
patterns
in
the
United
States
are
different
than
those
used
to
establish
many
of
the
Codex
tolerances,
it
is
not
necessary
to
harmonize
the
tolerances
with
Codex.
