Document ID: EPA-HQ-OPP-2003-0007-0001
Agency: epa
Document Type: Notice
Title: Pyrimethanil; Notice of Filing a Pesticide Petition to Establish a Tolerance for a Certain Pesticide Chemical in or on Food
Posted Date: 2003-02-14T05:00Z

7548
Federal
Register
/
Vol.
68,
No.
31
/
Friday,
February
14,
2003
/
Notices
conducted
via
oral
gavage
in
rabbits
with
dosages
of
0,
100,
300,
and
1,000
mg/
kg
bwt/
day.
The
NOAEL
for
maternal
toxicity
was
100
mg/
kg
bwt/
day
and
was
1,000
mg/
kg/
day
for
developmental
toxicity.
As
noted
above
this
NOAEL
is
based
on
fecal
alterations
and
an
abortion
in
a
single
dam
at
the
next
highest
dose
of
300
mg/
kg/
day.
The
dam
which
displayed
the
fecal
alterations
and
abortion
also
displayed
decreased
body
weight,
body
weight
gain
and
food
consumption
­
compared
to
the
group
mean
­
during
gestation.
These
decreases
occurred
even
prior
to
compound
administration.
These
decreases
in
body
weight,
body
weight
gain,
and
food
consumption,
prior
to
compound
administration,
all
indicate
an
animal
in
poor
health
and
this
poor
state
of
health,
rather
than
compound
exposure,
was
likely
the
reason
for
the
fecal
alterations
and
abortion.
No
teratogenic
effects
were
observed
at
any
dose
level.
4.
Reproductive
toxicity.
A
2
 
generation
reproduction
study
in
rats
was
conducted
with
dosages
of
0,
12,
118,
and
1,183
mg/
kg
bwt/
day.
No
impairment
of
reproductive
function
was
noted
at
any
dose.
The
parental
and
developmental
NOAEL
are
both
12
mg/
kg/
day.
Mild
effects
in
both
the
parents
and
pups
were
noted
at
118
mg/
kg/
day
and
consisted
of
an
increased
incidence
of
hepatic
centrilobular
hypertrophy
in
parents
and,
in
the
pups,
slightly
decreased
body
weight
and
body
weight
gain
(
7%)
in
F2
generation
only,
and
only
in
males.
At
1,183
mg/
kg/
day
paternal
effects
included
decreased
body
weights
and
food
consumption,
increased
liver
weights
and
increased
incidence
of
hepatic
centrilobular
hypertrophy
and
degeneration.
Pup
effects
at
this
dose
were
an
increase
in
pup
mortality
in
the
F2
only
and
a
decreased
body
weight
in
F1
and
F2.
5.
Reference
dose.
In
all
reproductive
studies,
the
NOAELs
for
developmental
effects
were
either
equal
to
or
higher
than
those
for
the
parents.
Therefore,
BAS
510
F
shows
no
selective
toxicity
for
the
young.
In
addition,
there
were
no
direct
neurotoxicity
effects
noted
in
either
the
acute
or
subchronic
neurotoxicity
studies.
Based
on
these
results,
no
additional
safety
factors
to
protect
children
are
warranted.
Since
the
reproductive
studies
NOAELs
are
higher
than
the
RfD
calculated
from
the
chronic
rat
study,
BASF
believes
the
RfD
of
0.05
mg/
kg/
day
is
also
appropriate
to
measure
safety
for
infants
and
children.
Therefore,
the
chronic
population
adjusted
dose
is
also
0.05
mg/
kg
bwt/
day.
F.
International
Tolerances
A
maximum
residue
level
has
not
been
established
for
BAS
510
F
in
any
crop
by
the
Codex
Alimentarius
Commission.

[
FR
Doc.
03
 
3694
Filed
2
 
13
 
03;
8:
45
am]

BILLING
CODE
6560
 
50
 
S
ENVIRONMENTAL
PROTECTION
AGENCY
[
OPP
 
2003
 
0007;
FRL
 
7289
 
1]

Pyrimethanil;
Notice
of
Filing
a
Pesticide
Petition
to
Establish
a
Tolerance
for
a
Certain
Pesticide
Chemical
in
or
on
Food
AGENCY:
Environmental
Protection
Agency
(
EPA).
ACTION:
Notice.

SUMMARY:
This
notice
announces
the
initial
filing
of
a
pesticide
petition
proposing
the
establishment
of
regulations
for
residues
of
pyrimethanil
in
or
on
various
food
commodities.
DATES:
Comments,
identified
by
docket
ID
number
OPP
 
2002
 
0007,
must
be
received
on
or
before
March
17,
2003.
ADDRESSES:
Comments
may
be
submitted
electronically,
by
mail,
or
through
hand
delivery/
courier.
Follow
the
detailed
instructions
as
provided
in
Unit
I.
of
the
SUPPLEMENTARY
INFORMATION.

FOR
FURTHER
INFORMATION
CONTACT:
Mary
Waller,
Registration
Division
(
7505C),
Office
of
Pesticide
Programs,
Environmental
Protection
Agency,
1200
Pennsylvania
Ave.,
NW.,
Washington,
DC
20460
 
0001;
telephone
number:
(
703)
308
 
9354;
e­
mail
address:
waller.
mary@
epa.
gov.

SUPPLEMENTARY
INFORMATION:

I.
General
Information
A.
Does
this
Action
Apply
to
Me?

You
may
be
affected
by
this
action
if
you
are
an
agricultural
producer,
food
manufacturer,
or
pesticide
manufacturer.
Potentially
affected
categories
and
entities
may
include,
but
are
not
limited
to:
 
Crop
production
(
NAICS
111)
 
Animal
production
(
NAICS
112)
 
Food
manufacturing
(
NAICS
311)
 
Pesticide
manufacturing
(
NAICS
32532)
This
listing
is
not
intended
to
be
exhaustive,
but
rather
provides
a
guide
for
readers
regarding
entities
likely
to
be
affected
by
this
action.
Other
types
of
entities
not
listed
in
the
table
could
also
be
affected.
The
North
American
Industrial
Classification
System
(
NAICS)
codes
have
been
provided
to
assist
you
and
others
in
determining
whether
or
not
this
action
might
apply
to
certain
entities.
If
you
have
questions
regarding
the
applicability
of
this
action
to
a
particular
entity,
consult
the
person
listed
under
FOR
FURTHER
INFORMATION
CONTACT.

B.
How
Can
I
Get
Copies
of
this
Document
and
Other
Related
Information?
1.
Docket.
EPA
has
established
an
official
public
docket
for
this
action
under
docket
identification
(
ID)
number
OPP
 
2003
 
0007.
The
official
public
docket
consists
of
the
documents
specifically
referenced
in
this
action,
any
public
comments
received,
and
other
information
related
to
this
action.
Although
a
part
of
the
official
docket,
the
public
docket
does
not
include
Confidential
Business
Information
(
CBI)
or
other
information
whose
disclosure
is
restricted
by
statute.
The
official
public
docket
is
the
collection
of
materials
that
is
available
for
public
viewing
at
the
Public
Information
and
Records
Integrity
Branch
(
PIRIB),
Rm.
119,
Crystal
Mall
#
2,
1921
Jefferson
Davis
Hwy.,
Arlington,
VA.
This
docket
facility
is
open
from
8:
30
a.
m.
to
4
p.
m.,
Monday
through
Friday,
excluding
legal
holidays.
The
docket
telephone
number
is
(
703)
305
 
5805.
2.
Electronic
access.
You
may
access
this
Federal
Register
document
electronically
through
the
EPA
Internet
under
the
``
Federal
Register''
listings
at
http://
www.
epa.
gov/
fedrgstr/.
An
electronic
version
of
the
public
docket
is
available
through
EPA's
electronic
public
docket
and
comment
system,
EPA
Dockets.
You
may
use
EPA
Dockets
at
http://
www.
epa.
gov/
edocket/
to
submit
or
view
public
comments,
access
the
index
listing
of
the
contents
of
the
official
public
docket,
and
to
access
those
documents
in
the
public
docket
that
are
available
electronically.
Although
not
all
docket
materials
may
be
available
electronically,
you
may
still
access
any
of
the
publicly
available
docket
materials
through
the
docket
facility
identified
in
Unit
I.
B.
1.
Once
in
the
system,
select
``
search,''
then
key
in
the
appropriate
docket
ID
number.
Certain
types
of
information
will
not
be
placed
in
the
EPA
Dockets.
Information
claimed
as
CBI
and
other
information
whose
disclosure
is
restricted
by
statute,
which
is
not
included
in
the
official
public
docket,
will
not
be
available
for
public
viewing
in
EPA's
electronic
public
docket.
EPA's
policy
is
that
copyrighted
material
will
not
be
placed
in
EPA's
electronic
public
docket
but
will
be
available
only
in
printed,
paper
form
in
the
official
public
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7549
Federal
Register
/
Vol.
68,
No.
31
/
Friday,
February
14,
2003
/
Notices
docket.
To
the
extent
feasible,
publicly
available
docket
materials
will
be
made
available
in
EPA's
electronic
public
docket.
When
a
document
is
selected
from
the
index
list
in
EPA
Dockets,
the
system
will
identify
whether
the
document
is
available
for
viewing
in
EPA's
electronic
public
docket.
Although
not
all
docket
materials
may
be
available
electronically,
you
may
still
access
any
of
the
publicly
available
docket
materials
through
the
docket
facility
identified
in
Unit
I.
B.
EPA
intends
to
work
towards
providing
electronic
access
to
all
of
the
publicly
available
docket
materials
through
EPA's
electronic
public
docket.
For
public
commenters,
it
is
important
to
note
that
EPA's
policy
is
that
public
comments,
whether
submitted
electronically
or
in
paper,
will
be
made
available
for
public
viewing
in
EPA's
electronic
public
docket
as
EPA
receives
them
and
without
change,
unless
the
comment
contains
copyrighted
material,
CBI,
or
other
information
whose
disclosure
is
restricted
by
statute.
When
EPA
identifies
a
comment
containing
copyrighted
material,
EPA
will
provide
a
reference
to
that
material
in
the
version
of
the
comment
that
is
placed
in
EPA's
electronic
public
docket.
The
entire
printed
comment,
including
the
copyrighted
material,
will
be
available
in
the
public
docket.
Public
comments
submitted
on
computer
disks
that
are
mailed
or
delivered
to
the
docket
will
be
transferred
to
EPA's
electronic
public
docket.
Public
comments
that
are
mailed
or
delivered
to
the
docket
will
be
scanned
and
placed
in
EPA's
electronic
public
docket.
Where
practical,
physical
objects
will
be
photographed,
and
the
photograph
will
be
placed
in
EPA's
electronic
public
docket
along
with
a
brief
description
written
by
the
docket
staff.

C.
How
and
To
Whom
Do
I
Submit
Comments?
You
may
submit
comments
electronically,
by
mail,
or
through
hand
delivery/
courier.
To
ensure
proper
receipt
by
EPA,
identify
the
appropriate
docket
ID
number
in
the
subject
line
on
the
first
page
of
your
comment.
Please
ensure
that
your
comments
are
submitted
within
the
specified
comment
period.
Comments
received
after
the
close
of
the
comment
period
will
be
marked
``
late.''
EPA
is
not
required
to
consider
these
late
comments.
If
you
wish
to
submit
CBI
or
information
that
is
otherwise
protected
by
statute,
please
follow
the
instructions
in
Unit
I.
D.
Do
not
use
EPA
Dockets
or
e­
mail
to
submit
CBI
or
information
protected
by
statute.
1.
Electronically.
If
you
submit
an
electronic
comment
as
prescribed
in
this
unit,
EPA
recommends
that
you
include
your
name,
mailing
address,
and
an
email
address
or
other
contact
information
in
the
body
of
your
comment.
Also
include
this
contact
information
on
the
outside
of
any
disk
or
CD
ROM
you
submit,
and
in
any
cover
letter
accompanying
the
disk
or
CD
ROM.
This
ensures
that
you
can
be
identified
as
the
submitter
of
the
comment
and
allows
EPA
to
contact
you
in
case
EPA
cannot
read
your
comment
due
to
technical
difficulties
or
needs
further
information
on
the
substance
of
your
comment.
EPA's
policy
is
that
EPA
will
not
edit
your
comment,
and
any
identifying
or
contact
information
provided
in
the
body
of
a
comment
will
be
included
as
part
of
the
comment
that
is
placed
in
the
official
public
docket,
and
made
available
in
EPA's
electronic
public
docket.
If
EPA
cannot
read
your
comment
due
to
technical
difficulties
and
cannot
contact
you
for
clarification,
EPA
may
not
be
able
to
consider
your
comment.
i.
EPA
Dockets.
Your
use
of
EPA's
electronic
public
docket
to
submit
comments
to
EPA
electronically
is
EPA's
preferred
method
for
receiving
comments.
Go
directly
to
EPA
Dockets
at
http://
www.
epa.
gov/
edocket,
and
follow
the
online
instructions
for
submitting
comments.
Once
in
the
system,
select
``
search,''
and
then
key
in
docket
ID
number
OPP
 
2003
 
0007.
The
system
is
an
``
anonymous
access''
system,
which
means
EPA
will
not
know
your
identity,
e­
mail
address,
or
other
contact
information
unless
you
provide
it
in
the
body
of
your
comment.
ii.
E­
mail.
Comments
may
be
sent
by
e­
mail
to
opp­
docket@
epa.
gov,
Attention:
Docket
ID
Number
OPP
 
2003
 
0007.
In
contrast
to
EPA's
electronic
public
docket,
EPA's
e­
mail
system
is
not
an
``
anonymous
access''
system.
If
you
send
an
e­
mail
comment
directly
to
the
docket
without
going
through
EPA's
electronic
public
docket,
EPA's
e­
mail
system
automatically
captures
your
e­
mail
address.
E­
mail
addresses
that
are
automatically
captured
by
EPA's
e­
mail
system
are
included
as
part
of
the
comment
that
is
placed
in
the
official
public
docket,
and
made
available
in
EPA's
electronic
public
docket.
iii.
Disk
or
CD
ROM.
You
may
submit
comments
on
a
disk
or
CD
ROM
that
you
mail
to
the
mailing
address
identified
in
Unit
I.
C.
2.
These
electronic
submissions
will
be
accepted
in
WordPerfect
or
ASCII
file
format.
Avoid
the
use
of
special
characters
and
any
form
of
encryption.
2.
By
mail.
Send
your
comments
to:
Public
Information
and
Records
Integrity
Branch
(
PIRIB)
(
7502C),
Office
of
Pesticide
Programs
(
OPP),
Environmental
Protection
Agency,
1200
Pennsylvania
Ave.,
NW.,
Washington,
DC
20460
 
0001,
Attention:
Docket
ID
Number
OPP
 
2003
 
0007.
3.
By
hand
delivery
or
courier.
Deliver
your
comments
to:
Public
Information
and
Records
Integrity
Branch
(
PIRIB),
Office
of
Pesticide
Programs
(
OPP),
Environmental
Protection
Agency,
Rm.
119,
Crystal
Mall
#
2,
1921
Jefferson
Davis
Hwy.,
Arlington,
VA,
Attention:
Docket
ID
Number
OPP
 
2003
 
0007.
Such
deliveries
are
only
accepted
during
the
docket's
normal
hours
of
operation
as
identified
in
Unit
I.
B.
1.

D.
How
Should
I
Submit
CBI
to
the
Agency?

Do
not
submit
information
that
you
consider
to
be
CBI
electronically
through
EPA's
electronic
public
docket
or
by
e­
mail.
You
may
claim
information
that
you
submit
to
EPA
as
CBI
by
marking
any
part
or
all
of
that
information
as
CBI
(
if
you
submit
CBI
on
disk
or
CD
ROM,
mark
the
outside
of
the
disk
or
CD
ROM
as
CBI
and
then
identify
electronically
within
the
disk
or
CD
ROM
the
specific
information
that
is
CBI).
Information
so
marked
will
not
be
disclosed
except
in
accordance
with
procedures
set
forth
in
40
CFR
part
2.
In
addition
to
one
complete
version
of
the
comment
that
includes
any
information
claimed
as
CBI,
a
copy
of
the
comment
that
does
not
contain
the
information
claimed
as
CBI
must
be
submitted
for
inclusion
in
the
public
docket
and
EPA's
electronic
public
docket.
If
you
submit
the
copy
that
does
not
contain
CBI
on
disk
or
CD
ROM,
mark
the
outside
of
the
disk
or
CD
ROM
clearly
that
it
does
not
contain
CBI.
Information
not
marked
as
CBI
will
be
included
in
the
public
docket
and
EPA's
electronic
public
docket
without
prior
notice.
If
you
have
any
questions
about
CBI
or
the
procedures
for
claiming
CBI,
please
consult
the
person
listed
under
FOR
FURTHER
INFORMATION
CONTACT.

E.
What
Should
I
Consider
as
I
Prepare
My
Comments
for
EPA?

You
may
find
the
following
suggestions
helpful
for
preparing
your
comments:
1.
Explain
your
views
as
clearly
as
possible.
2.
Describe
any
assumptions
that
you
used.
3.
Provide
copies
of
any
technical
information
and/
or
data
you
used
that
support
your
views.

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Federal
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Vol.
68,
No.
31
/
Friday,
February
14,
2003
/
Notices
4.
If
you
estimate
potential
burden
or
costs,
explain
how
you
arrived
at
the
estimate
that
you
provide.
5.
Provide
specific
examples
to
illustrate
your
concerns.
6.
Make
sure
to
submit
your
comments
by
the
deadline
in
this
notice.
7.
To
ensure
proper
receipt
by
EPA,
be
sure
to
identify
the
docket
ID
number
assigned
to
this
action
in
the
subject
line
on
the
first
page
of
your
response.
You
may
also
provide
the
name,
date,
and
Federal
Register
citation.

II.
What
Action
is
the
Agency
Taking?

EPA
has
received
a
pesticide
petition
as
follows
proposing
the
establishment
and/
or
amendment
of
regulations
for
residues
of
a
certain
pesticide
chemical
in
or
on
various
food
commodities
under
section
408
of
the
Federal
Food,
Drug,
and
Cosmetic
Act
(
FFDCA),
21
U.
S.
C.
346a.
EPA
has
determined
that
this
petition
contains
data
or
information
regarding
the
elements
set
forth
in
FFDCA
section
408(
d)(
2);
however,
EPA
has
not
fully
evaluated
the
sufficiency
of
the
submitted
data
at
this
time
or
whether
the
data
support
granting
of
the
petition.
Additional
data
may
be
needed
before
EPA
rules
on
the
petition.

List
of
Subjects
Environmental
protection,
Agricultural
commodities,
Feed
additives,
Food
additives,
Pesticides
and
pests,
Reporting
and
recordkeeping
requirements.

Dated:
February
3,
2003.
Debra
Edwards,
Acting
Director,
Registration
Division,
Office
of
Pesticide
Programs.

Summary
of
Petition
The
petitioner
summary
of
the
pesticide
petition
is
printed
below
as
required
by
FFDCA
section
408(
d)(
3).
The
summary
of
the
petition
was
prepared
by
the
petitioner
and
represents
the
view
of
the
petitioner.
The
petition
summary
announces
the
availability
of
a
description
of
the
analytical
methods
available
to
EPA
for
the
detection
and
measurement
of
the
pesticide
chemical
residues
or
an
explanation
of
why
no
such
method
is
needed.

Janssen
Pharmaceutica
Inc.

PP
2F6480
EPA
has
received
a
pesticide
petition
(
2F6480)
from
Janssen
Pharmaceutica
Inc.,
Plant
and
Material
Protection
Division,
1125
Trenton­
Harbourton
Road,
Titusville,
NJ
08560
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
by
establishing
tolerances
for
residues
of
the
fungicide,
pyrimethanil
(
4,6­
dimethyl­
N­
phenyl­
2­
pyrimidinamine)
in
or
on
the
raw
agricultural
commodities
citrus
fruits
(
calamondin,
citrus
citron,
citrus
hybrids,
grapefruit,
kumquat,
lemon,
lime,
mandarin,
sour
and
sweet
oranges,
pummelo
and
Satsuma
mandarin)
at
6
parts
per
million
(
ppm),
pome
fruit
(
apples,
pears,
oriental
pears,
crabapples,
loquats,
mayhaws,
and
quince)
wet
pomace
at
12
ppm,
and
pome
fruit
(
apples,
pears,
oriental
pears,
crabapples,
loquats,
mayhaws,
and
quince)
at
3
ppm.
EPA
has
determined
that
the
petition
contains
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
petition.
Additional
data
may
be
needed
before
EPA
rules
on
the
petition.

A.
Residue
Chemistry
1.
Plant
metabolism.
The
metabolic
profile
of
pyrimethanil
has
been
investigated
following
application
to
five
different
crops
(
apple,
carrots,
grapes,
lettuce
and
tomatoes)
and
is
well
understood.
In
plants,
pyrimethanil
is
the
only
significant
residue
ranging
from
essentially
all
of
the
Total
Radioactive
Residues
(
TRR)
in
carrots
and
tomatoes
to
44%
in
lettuce.
Limited
metabolism
of
pyrimethanil
occurs
with
minor
amounts
(
less
than
10%)
of
the
phenyl
and
pyrimidyl
hydroxylated
metabolites
(
AE
C614276,
AE
C614277,
AE
C614278,
and
AE
C621312)
being
released
after
acid
hydrolysis.
Analysis
of
the
foliage
from
apples
and
carrots
confirmed
that
the
metabolism
of
pyrimethanil
in
plants
proceeded
primarily
via
hydroxylation
of
the
aromatic
ring
structures
as
well
as
the
methyl
groups.
2.
Analytical
method.
The
plant
metabolism
studies
indicated
that
analysis
for
the
parent
compound,
pyrimethanil
was
sufficient
to
enable
the
assessment
of
the
relevant
residues
in
crop
commodities.
For
citrus,
the
pyrimethanil
was
extracted
with
acetone,
the
extract
acidified
and
washed
with
isohexane
and
basified
to
enable
solvent
partition.
After
solvent
exchange
to
ethyl
acetate,
the
residue
is
determined
using
GC­
MS.
For
pome
fruits,
the
pyrimethanil
was
extracted
directly
with
ethyl
acetate/
isohexane
(
1:
1),
dried,
and
analyzed
for
residues
with
GC­
MS.
The
limit
of
quantitation
is
0.05
ppm.
These
methods
allow
detection
and
measurement
of
residues
in
or
on
agricultural
commodities
at
or
above
the
proposed
tolerance
level.
3.
Magnitude
of
residues.
Magnitude
of
residue
trials
were
conducted
for
pyrimethanil
on
apples,
pears,
and
citrus
(
lemons,
oranges
(
navels
and
valencias),
tangerines,
tangelos,
and
grapefruit).
Trials
were
conducted
in
the
major
producing
states
which
together
represent
97%,
70%,
and
75%
of
the
citrus,
apple
and
pear
domestic
production,
respectively.
Samples
were
collected
according
to
good
agricultural
practices
at
harvest
and/
or
following
a
postharvest
treatment.
The
pre­
harvest
interval
(
PHI)
for
pome
fruit
was
7
days
following
application
of
the
fungicide
at
the
proposed
label
rate,
to
approximate
maximum
field
residues.
The
proposed
PHI
for
pome
fruit
is
72
days.
Samples
were
harvested
at
maturity
and
analyzed
with
a
method
having
an
level
of
quantitation
(
LOQ)
of
0.05
ppm
pyrimethanil.
Residues
in
the
raw
agricultural
commodity
(
RAC)
samples
(
range,
maximum
and
average)
are
discussed
per
crop
grouping
below.
i.
Citrus
fruits
(
calamondin,
citrus
citron,
citrus
hybrids,
grapefruit,
kumquat,
lemon,
lime,
mandarin,
sour
and
sweet
oranges,
pummelo
and
Satsuma
mandarin).
Nine
trials
were
conducted
on
citrus
during
2001.
An
end
use
formulation
containing
400
gram/
liter
or
3.34
lbs/
active
ingredient/
gallon
of
pyrimethanil
was
applied
by
drench,
dip
and/
or
line
spray
in
water,
storage
wax
or
shipping
wax.
Multiple
treatments
(
single,
double
and
triple
applications)
were
investigated.
A
maximum
of
ten
different
multiple
treatment
scenarios
were
investigated
for
lemons,
seven
for
oranges,
and
five
for
grapefruit.
Fruit
were
washed
between
treatments
only
when
this
was
typical
of
commercial
packinghouse
operations.
The
maximum
rates
applied
were
1,000
ppm
in
drench
and
dip
tanks,
and
2,000
ppm
in
any
type
of
line
spray.
The
maximum
proposed
use
recommendations
are
for
a
4
minute
drench
at
500
ppm,
2
minute
dip
at
1,000
ppm,
and/
or
2,000
ppm
line
spray
for
water
or
storage
and
shipping
wax,
with
a
maximum
of
three
applications.
Whole
fruit
and
edible
pulp
were
analyzed
separately
for
pyrimethanil
residues.
In
the
whole
fruit
samples,
maximum
residues
were
6.0
ppm
for
the
proposed
applications,
and
0.76
ppm
for
edible
pulp.
Mean
pyrimethanil
residues
ranged
from
1.1
ppm
for
an
single
aqueous
line
spray
applied
with
a
20,000
ppm
treating
solution
to
5.45
ppm
for
a
triple
treatment
that
included
a
drench
(
1,000
ppm),
dip
(
1,000
ppm),
and
2,000
ppm
wax
line
spray.
A
single
orange
trial
was
established
in
Florida
as
a
processing
study.
Pyrimethanil
was
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Vol.
68,
No.
31
/
Friday,
February
14,
2003
/
Notices
applied
as
a
dual
application
at
rates
of
2,000
and
4,000
ppm
active
ingredient
(
a.
i.)
in
aqueous
and
wax
line
sprays,
respectively.
This
rate
is
the
maximum
for
the
aqueous
treatment
and
two
times
the
proposed
label
rate
for
wax
incorporation.
Mean
pyrimethanil
residue
levels
found
in/
on
the
samples
were:
Whole
citrus
fruits
7.46
ppm,
dried
pulp
2.93,
orange
juice
0.05
ppm
and
citrus
oil
131
ppm.
No
pyrimethanil­
derived
residue
concentrated
from
the
whole
fruit
into
the
orange
juice
or
dried
pulp.
However,
the
pyrimethanil
residues
concentrated
from
the
whole
oranges
into
the
citrus
oil
by
a
factor
of
17.5.
Citrus
oil
is
not
considered
as
a
ready­
to­
eat
food
commodity
and
since
none
of
the
of
the
processed
food
products
are
likely
to
contain
pyrimethanil
residues
above
the
proposed
citrus
tolerance
of
6.0
ppm
in
the
raw
agricultural
commodity
of
whole
fruit
utilizing
dilution
factors,
tolerances
are
not
necessary
for
citrus
oil.
ii.
Pome
fruit
(
apples,
pears,
Oriental
pears,
crabapples,
loquats,
mayhew,
and
quince).
Ten
trials
were
established
for
this
study,
four
in
Washington,
four
in
California,
and
two
in
New
York.
Of
the
10
trials,
4
were
conducted
on
pears
and
6
on
apples.
A
pre­
harvest
formulation
of
pyrimethanil
was
applied
to
the
apple
or
pear
trees
during
a
single
application,
at
a
nominal
rate
of
0.40
lb
of
a.
i.,
7
days
prior
to
harvest.
Mean
pyrimethanil
residue
levels
found
in
or
on
the
apple
fruit
following
both
preharvest
and
postharvest
applications
ranged
from
0.49
ppm
for
a
single
aqueous
line
spray
at
1,000
ppm
a.
i.
to
1.44
ppm
for
the
dual
treatment
consisting
of
a
drench
(
1,000
ppm)
followed
by
an
aqueous
line
spray
(
1,000
ppm).
Individual
sample
residues
ranged
from
a
low
of
0.11
ppm
for
the
1,000
ppm
aqueous
line
spray
to
2.84
ppm
for
the
dual
treatment
of
a
1,000
ppm
drench
followed
by
a
2,000
ppm
wax
application.
The
limit
of
quantitation
of
the
analytical
method
was
0.05
ppm.
A
single
trial
was
established
in
Washington
as
a
processing
study.
Pyrimethanil
was
applied
to
apple
trees
four
times
prior
to
harvest.
Applications
were
made
at
a
nominal
rate
of
2.0
lb
a.
i./
Acre,
with
7
days
between
applications.
This
rate
is
approximately
five
times
the
proposed
label
application
rate.
Mean
pyrimethanil
residue
levels
found
in
or
on
the
samples
were:
Whole
apple
fruit
0.17
ppm,
wet
pomace
0.69
ppm,
and
juice
0.06
ppm.
No
pyrimethanilderived
residue
concentrated
from
the
whole
fruit
into
the
apple
juice.
However,
the
pyrimethanil
residues
concentrated
from
the
whole
apples
into
the
wet
pomace
by
a
factor
of
4.

B.
Toxicological
Profile
1.
Acute
toxicity.
Pyrimethanil
is
of
low
acute
toxicity
placing
the
active
ingredient
in
Toxicity
Category
II,
III
and
IV.
Pyrimethanil
is
non­
irritating
to
the
eyes
and
skin
and
is
not
a
skin
sensitizer.
Acute
neurotoxicity.
Groups
of
10
rats/
sex/
group
were
dosed
once
by
oral
gavage
at
dose
levels
of
0,
30,
100,
1,000
milligrams/
kilogram
(
mg/
kg)
of
pyrimethanil
bodyweight.
On
the
day
of
dosing,
high
dose
animals
experienced
transient
behavioral
effects
attributable
to
receipt
of
a
substantial
bolus
dose
of
test
substance.
No
histopathological
lesions
accompanied
these
transient
behavioral
changes.
The
no
observed
adverse
effect
level
(
NOAEL)
was
100
mg/
kg
due
to
reduced
body
temperature
for
males.
The
NOAEL
was
30
mg/
kg.
2.
Genotoxicity.
Pyrimethanil
is
not
mutagenic
or
genotoxic
in
any
assay
in
either
the
presence
or
absence
of
metabolic
activation.
3.
Reproductive
and
developmental
toxicity.
Pyrimethanil
is
not
a
developmental
or
reproductive
toxicant.
i.
Teratology
­
rat.
Thirty
Sprague
Dawley
rats/
group
received
doses
of
0,
7,
85,
1,000
mg/
kg
of
pyrimethanil
by
gavage
from
gestation
days
(
GD)
6­
15.
At
the
highest
dose
tested,
reduced
maternal
body
weight
gain
was
observed
during
GD6­
15,
along
with
a
slight
but
statistically
significant
decrease
in
food
consumption,
hair
loss,
hunched
posture,
slight
emaciation,
and
slightly
reduced
mean
fetal
body
weight.
The
maternal
and
developmental
NOAEL
was
85
mg/
kg.
ii.
Teratology
­
rabbit.
Groups
of
at
least
18
time­
mated
New
Zealand
White
rabbits
received
oral
gavage
doses
of
0,
7,
45,
or
300
mg/
kg/
day
pyrimethanil
over
gestation
days
(
GD)
7­
19.
At
the
highest
dose
tested,
there
was
a
decrease
in
body
weight
gain,
production
of
feces
and
food
consumption.
Three
females
were
euthanized
due
to
severe
emaciation.
The
highest
dose,
300
mg/
kg/
day
exceeded
the
maternal
maximum
tolerated
dose
(
MTD).
The
maternal
NOAEL
was
45
mg/
kg/
day
due
to
reduced
fecal
production
in
1/
3
of
the
animals.
The
high
dose
resulted
in
reduced
mean
fetal
body
weight,
increased
incidence
of
runts,
delayed
skeletal
ossification
and
incidence
of
fetuses
with
13
thoracic
vertebrae
and
ribs.
The
maternal
NOAEL
was
7
mg/
kg/
day.
The
developmental
NOAEL
was
45
mg/
kg/
day.
iii.
Two­
generation
reproduction
­
rat.
Three
groups
of
30
Sprague­
Dawley
rats
per
sex
received
dietary
exposure
to
pyrimethanil
at
levels
of
0,
1.7,
20.9,
or
266.7
mg/
kg/
day.
In
the
parental
generation
at
the
highest
dose
tested
there
was
a
statistically
significant
decrease
in
mean
body
weight
gain
in
both
sexes.
Mean
pup
weights,
observed
on
PND1
through
weaning,
were
reduced,
though
were
within
the
range
of
historical
controls.
In
the
F1
generation
at
the
highest
dose
tested,
mean
body
weights
and
mean
food
consumption
were
reduced.
Though
the
mean
score
for
the
combined
sexes
was
the
same
as
the
controls,
a
marginally
different
air­
righting
reflex
at
PND11
associated
with
reduced
body
weight
was
seen
in
high
dose
male
pups.
The
NOAEL
for
maternal
and
developmental
toxicity
was
20.9
mg/
kg/
day.
The
reproductive
NOAEL
was
266.7
mg/
kg/
day.
4.
Subchronic
toxicity
 
i.
28
 
Day
dietary
rat.
Five
Sprague­
Dawley
rats/
sex/
group
received
dietary
exposure
to
pyrimethanil
for
28
days
at
0,
844,
1,161,
1,500,
and
2,710
mg/
kg/
day.
All
doses
exceeded
the
maximum
tolerated
dose.
Severe
emaciation
was
observed
at
all
dose
levels.
Body
weight
gains
and
food
consumption
were
reduced.
Liver
and
thyroid
histopathology
were
observed,
along
with
reduced
hemoglobin,
MCV
and
MCH.
Kidney,
adrenal
and
liver
weights
were
altered.
No
NOEL
or
NOAEL
was
achieved.
ii.
90
 
Day
dietary
rat.
Ten
Sprague­
Dawley
rats/
sex/
group
received
pyrimethanil
in
the
diet
at
dose
levels
of
0,
5.4­
6.8,
54.5­
66.7,
and
545­
667
mg/
kg/
day
(
males
and
females,
respectively).
High
dose
animals
had
reduced
body
weight
gain
and
food
consumption,
increased
urinary
protein
in
males,
colored
urine
(
not
blood
or
bilirubin)
and
minimal
hepatocellular
hypertrophy.
The
NOAEL
in
males
was
54.5­
66.7
(
males
and
females,
respectively)
due
to
colored
urine
and
a
low
incidence
of
minimal
centrilobular
hepatocellular
hypertrophy.
The
NOAEL
was
5.4
mg/
kg/
day
(
males)
­
6.8
mg/
kg/
day
(
females).
iii.
28­
Day
dietary­
mouse.
Five
CD­
1
mice/
sex/
group
received
dietary
doses
of
0,
167­
236,
567­
667,
1960­
2357
mg/
kg/
day,
males
and
females
respectively,
for
28
days
(
all
the
mice
in
one
additional
high
dose
group,
30,000
ppm,
died
within
the
first
week
of
the
study).
At
1960­
2357
mg/
kg/
day,
animals
experienced:
body
weight
loss
(
females),
decreased
body
weight
gain
during
the
first
2
weeks
(
males),
a
statistically
significant
decrease
in
cholesterol,
statistically
significant
decreases
in
relative
liver
weights
(
females),
pigmentation
of
thyroid
follicles,
urolithiasis,
moderate
urothelial
hyperplasia
in
urinary
bladder,
and
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slight
kidney
tubular
degeneration
(
females).
The
NOAEL
was
167­
236
mg/
kg/
day.
iv.
90
 
Day
dietary­
mouse.
Twenty
CD­
1
mice/
sex/
group
received
pyrimethanil
diet
exposure
at
dose
levels
of
0,
12­
18,
139­
203,
1,864­
2,545
mg/
kg/
day
males­
females
for
90
days.
At
the
high
dose,
animals
had
decreased
body
weight
and
increased
food
consumption,
cholesterol
and
total
bilirubin.
High
dose
females
had
increased
relative
liver
weights.
Histopathology
in
the
high
dose
animals
was
found
in
the
kidneys,
liver,
thyroid,
and
urinary
bladder.
High
dose
males
had
slight
urinary
tract
tubular
dilation
and
slight
to
moderate
hyperplasia
of
bladder
epithelium.
The
NOAEL
was
determined
to
be
12
mg/
kg/
day
(
males)
­
18
mg/
kg/
day
(
females).
Based
on
mild
hepatic
glycogen
depletion,
the
NOAEL
was
139­
203
mg/
kg/
day
(
males
and
females,
respectively).
v.
90
 
Day
dietary­
dog.
Four
beagle
dogs/
sex/
group
received
pyrimethanil
by
gavage
for
90
days
at
doses
of
0,
6,
80,
1,000
mg/
kg/
day.
The
high
dose
was
lowered
to
800
mg/
kg/
day
on
day
7
due
to
frequent
and
consistent
vomiting.
Decreased
body
weight,
food,
and
water
consumption
were
observed.
Males
had
a
significant
reduction
in
phosphate,
while
females
experienced
a
slight
reduction
in
sodium,
anion
gap
and
total
protein.
At
80
mg/
kg/
day,
infrequent
vomiting
after
dosing
and
decreased
water
consumption
were
observed.
After
4
weeks
of
dosing
at
80
mg/
kg/
day,
males
had
significantly
reduced
phosphate.
The
NOAEL
was
80
mg/
kg/
day.
The
NOEL
was
6
mg/
kg/
day.
vi.
Subchronic
neurotoxicity.
Groups
of
12
Sprague­
Dawley
rats
per
sex
were
treated
for
13
weeks
with
pyrimethanil
via
the
diet
at
0,
4,
38.7­
44.3,
391.9­
429.9
mg/
kg/
day
(
males
and
females,
respectively).
There
were
no
treatmentrelated
findings
in
behavioral
assessments,
neuropathology
or
brain
morphometrics.
The
NOAEL
for
this
study
is
38.7­
44.3
mg/
kg/
day
(
males
and
females,
respectively)
based
upon
decreased
body
weight
and
food
consumption
in
the
high
dose
group.
vii.
Dermal
toxicity
evaluation.
No
dermal
studies
have
been
conducted
for
pyrimethanil.
5.
Chronic
toxicity
 
i.
Chronic
toxicity
­
dog.
Four
beagle
dogs/
sex/
group
received
pyrimethanil
by
gavage
at
levels
of
0,
2,
30,
or
250
mg/
kg/
day
for
12
months.
The
high
dose
was
reduced
from
400
to
250
mg/
kg/
day
on
day
8
of
treatment
due
to
excessive
vomiting
during
the
first
week
of
treatment.
At
the
high
dose,
there
was
a
decrease
in
mean
body
weight
gain
and
mean
consumption
of
food
and
water.
The
NOAEL
for
the
study
was
30
mg/
kg/
day,
with
the
high
dose
of
250
mg/
kg/
day
being
the
NOAEL.
ii.
Combined
chronic
toxicity/
oncogenicity
­
rat.
Seventy
Sprague­
Dawley
rats/
sex/
group
received
pyrimethanil
by
diet
at
levels
of
0,
1.3­
1.8,
17­
22,
and
221­
291
mg/
kg/
day
(
males
and
females,
respectively)
for
2
years.
At
the
highest
dose
tested,
body
weight
gain
and
food
consumption
were
decreased.
Absolute
liver
weights
were
increased.
Histopathology
revealed
centrilobular
hepatocyte
hypertrophy,
increased
incidence
of
eosinophilic
foci
(
males),
thyroid
follicular
hyperplasia,
hypertrophy
and
colloid
depletion,
and
the
presence
of
a
brown
pigment,
identified
as
lipofuscin
in
thyroid
follicular
cell
epithelium.
There
was
a
statistically
significant,
dose­
dependent
increase
in
the
incidence
of
benign
thyroid
follicular
cell
adenomas.
There
was
no
increased
incidence
in
any
malignant
tumor
or
increase
in
tumor
multiplicity
as
a
result
of
daily
dietary
ingestion
of
pyrimethanil
at
any
dose
level.
The
results
of
special
studies,
discussed
below,
demonstrate
that
the
benign
thyroid
tumors
are
likely
a
secondary
result
of
a
disruption
of
thyroid­
pituitary
homeostasis,
a
wellknown
threshold­
mediated
mechanism.
The
NOAEL
was
17
mg/
kg/
day
(
males)
and
22
mg/
kg/
day
(
females).
iii.
Oncogenicity
­
mouse.
Fifty­
one
CD­
1
mice/
sex/
group
received
pyrimethanil
by
diet
at
0,
16,
160,
and
1,600
ppm
(
corresponding
to
0,
2­
2.5,
20­
24.9,
and
210.9­
253.8
mg/
kg/
day
in
males
and
females,
respectively).
There
was
an
increase
in
the
number
of
high
dose
male
deaths
caused
by
urogenital
tract
lesions.
Urinary
bladder
histopathology
on
those
dying
during
the
course
of
the
study
indicates
an
increase
in
the
incidence
of
male
urinary
bladder
distension,
cystitis,
urothelial
hyperplasia
and
inflammation
of
the
penis.
These
findings
are
consistent
with
the
findings
of
both
the
28­
and
90­
day
studies
indicating
that
high
dose
administration
of
pyrimethanil
resulted
in
urolith
formation
leading
to
irritation,
distension
and
hyperplasia
of
the
urinary
bladder
and
urinary
tract.
Chronic
dietary
treatment
with
pyrimethanil
produced
no
increased
incidence
of
tumor­
bearing
mice
nor
of
any
specific
tumor
type
suggestive
of
a
carcinogenic
effect.
The
NOAEL
for
both
sexes
was
20­
24.9
mg/
kg/
day
(
males
and
females,
respectively).
iv.
Special
studies.
Since
rodent
thyroid
tumors
are
fairly
common,
and
since
the
EPA
has
established
that
five
lines
of
evidence
are
required
to
prove
the
thyroid­
pituitary
disruption
mode
of
action
for
rodent
thyroid
tumors,
special
studies
were
undertaken
a.
Thyroid
mechanistic
study
(
14­
Day).
Sprague
Dawley
rats
received
378.5
mg/
kg/
day
of
pyrimethanil
for
14
days
to
study
the
effects
of
pyrimethanil
on
the
thyroid
and
liver
microsomal
enzymes.
An
increase
in
the
levels
of
UDPGT
and
a
corresponding
statistically
significant
increase
in
liver
weight
were
observed.
Thyroid
hormones
T4
and
T3
were
decreased,
while
TSH
levels
were
significantly
increased.
All
effects
were
shown
to
be
reversible.
b.
Dietary
thyroid
function
test
using
perchlorate
discharge
(
7­
Day).
Sprague
Dawley
rats
received
509
mg/
kg/
day
pyrimethanil
or
177
mg/
kg/
day
propylthiouracil,
or
109
mg/
kg/
day
phenobarbital
in
order
to
study
the
function
of
the
thyroid
gland.
The
animals
fed
pyrimethanil
had
43%
decreased
body
weight
gain,
21%
decreased
food
consumption
and
a
150%
increase
in
uptake
of
iodine­
125.
There
was
no
significant
discharge
of
radioactive
iodine
from
the
thyroid
after
administration
of
perchlorate.
The
required
five
lines
of
evidence
to
support
the
threshold
mode
of
action
for
thyroid
pituitary
disruption
and
rat
thyroid
tumors
are
satisfied
in
the
pyrimethanil
studies.
EPA's
final
rule
establishing
a
tolerance
for
pyrimethanil
in
wine
stated
that
``
The
Agency's
Carcinogenicity
Peer
Review
Committee
(
CPRC)
chose
a
non­
linear
approach
Margin
of
Exposure
(
MOE)
based
on
a
NOAEL
of
17
mg/
kg/
day
for
increased
incidences
of
thyroid
tumors
in
rats.
The
MOE
methodology
was
selected
because
of
thyroid
tumors
associated
with
administration
of
pyrimethanil
in
the
rat,
which
may
be
due
to
a
disruption
in
the
thyroid­
pituitary
status.
This
chemical
has
been
classified
as
a
Group
C
chemical
(
possible
human
carcinogen)
and
a
non­
linear
methodology
(
MOE)
was
applied
for
the
estimation
of
human
cancer
risk.
The
estimated
MOE
does
not
exceed
the
Agency's
level
of
concern
and
therefore,
EPA
has
a
reasonable
certainty
that
no
harm
will
result
from
exposures
to
residues
of
pyrimethanil.''
6.
Animal
metabolism.
Pyrimethanil
is
rapidly
metabolized
and
excreted
from
lactating
dairy
cows.
The
observed
total
radioactive
residues
in
edible
tissues
and
milk
were
as
follows:
Milk
­
maximum
residue
of
0.069
ppm;
liver
­
0.363
ppm;
kidney
0.249
ppm
and
muscle
0.017
ppm.
The
metabolic
pathway
is
similar
to
that
of
plants
involving
hydroxylation
of
the
phenyl
and
pyrimidine
rings
as
well
as
hydroxylation
of
the
methyl
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Notices
substituents.
Further
metabolic
reactions
occur
including
cleavage
of
the
phenyl
ring
to
produce
substituted
pyrimidines.
The
major
metabolite
was
AE
C614276
(
46%
of
the
kidney
residues,
63%
of
the
milk
residues)
resulting
from
hydroxylation
of
the
phenyl
ring.
Hydroxylation
of
the
pyrimidinyl
ring
of
pyrimethanil
resulted
in
formation
of
minor
amounts
of
AE
C614277.
Hydroxylation
of
the
methyl
groups
of
pyrimethanil
resulted
in
formation
of
minor
amounts
of
AE
C614278.
Hydroxylation
of
the
methyl
groups
of
AE
C614276
resulted
in
formation
of
minor
amounts
of
AE
C614800.
7.
Metabolite
toxicology.
The
primary
residue
of
concern
in
both
crop
and
animal
commodities
is
pyrimethanil.
In
the
animal
metabolism,
since
major
metabolites
are
produced
following
the
oral
administration
of
pyrimethanil,
toxicology
data
for
metabolites
are
completely
supported
by
data
obtained
for
pyrimethanil.
8.
Endocrine
disruption.
Chronic,
life
span,
and
multi­
generational
bioassays
in
mammals
and
acute
and
subchronic
studies
on
aquatic
organisms
and
wildlife
did
not
reveal
endocrine
effects.
Any
endocrine
related
effects
would
have
been
detected
in
this
definitive
array
of
required
tests.
The
probability
of
any
such
effect
due
to
agricultural
uses
of
pyrimethanil
is
negligible.

C.
Aggregate
Exposure
1.
Dietary
exposure.
Tolerances
are
proposed
under
40
CFR
part
180
for
pyrimethanil
in
or
on
citrus
fruits
and
pome
fruits
following
postharvest
application.
An
import
tolerance
for
wine
grapes
has
been
approved
by
the
EPA.
A
petition
for
registration
of
pyrimethanil
on
bananas
is
pending
at
EPA.
In
March
2002,
registration
applications
and
tolerance
petitions
were
filed
for
tree
nuts,
bulb
vegetables,
grapes,
stone
fruits
(
except
cherries),
pome
fruit
(
preharvest
application),
tuberous
and
corm
vegetables,
strawberries,
and
tomatoes.
There
are
no
residential
uses
proposed
for
pyrimethanil.
Therefore,
potential
human
risk
scenarios
cover
aggregate
exposure
from
food
residues
and
drinking
water.
i.
Food.
Refined
estimates
of
acute
dietary
exposure
from
potential
pyrimethanil
residues
with
the
addition
of
postharvest
uses
on
citrus
and
pome
fruits
are
all
well
under
100%
of
the
acute
reference
dose
(
RfD)
at
the
99.9th
percentile.
The
most
highly
exposed
sub
population
of
non­
nursing
infants
utilizes
13.35%
of
the
RfD,
while
the
U.
S.
population
utilizes
6.1%.
These
potential
dietary
exposures
were
estimated
in
a
Tier
3
Monte
Carlo
risk
assessment
using
the
Dietary
Exposure
Evaluation
Model
(
DEEM)
software
(
Novigen
2001).
The
1994
 
96,
1998
Continuing
Surveys
of
Food
Intake
by
Individuals
(
CSFII)
consumption
data
from
USDA
was
used
which
includes
the
Supplemental
Children's
Survey
(
1998).
Residue
values
included
in
the
assessment
were
distributions
of
the
field
trail
values
incorporating
percent
crop
treated
(
PCT)
as
zeroes
for
all
nonblended
and
partially
blended
items.
Blended
items
were
included
as
the
average
residue
and
adjusted
for
PCT.
These
PCT
values
are
the
anticipated
market
share
of
pyrimethanil
for
the
crops
at
market
maturity
(
5
years).
Concentration
factors
derived
from
processing
studies
were
included
where
appropriate.
Secondary
residues
for
meat
and
milk
were
included
in
the
assessment.
These
were
calculated
using
theoretical
dietary
burdens
from
sensible
diets
for
beef
and
dairy
cattle
and
tissue
to
feed
ratios
from
the
ruminant
feeding
study.
Refined
chronic
dietary
exposure
estimates
resulting
from
the
proposed
uses
of
pyrimethanil
are
well
within
acceptable
limits
for
all
population
subgroups
examined.
The
most
highly
exposed
group
of
non­
nursing
infants
utilized
0.9%
of
the
reference
dose
with
the
U.
S.
population
utilizing
0.2%
of
the
reference
dose.
A
Tier
3
chronic
analysis
was
done
using
the
DEEM
software,
(
Novigen
2001).
The
1994
 
96,
1998
CSFII
consumption
data
from
USDA
were
used.
Average
anticipated
residue
values
were
calculated
from
the
appropriate
field
trial
studies
conducted
for
pyrimethanil.
The
average
residue
values
were
adjusted
by
the
projected
PCT
at
product
maturity.
Concentration
factors
derived
from
processing
studies
were
included
where
appropriate.
Secondary
residues
were
calculated
using
theoretical
dietary
burdens
derived
from
sensible
diets
for
beef
and
dairy
cattle
and
tissue
to
feed
ratios
from
the
ruminant
feeding
study.
ii.
Drinking
water.
EPA's
Standard
Operating
Procedure
(
SOP)
for
Drinking
Water
Exposure
and
Risk
Assessments
was
followed
to
perform
the
Tier
One
drinking
water
assessment.
This
SOP
uses
a
variety
of
tools
to
conduct
drinking
water
assessments,
including
water
models
such
as
Screening
Concentrations
in
Ground
Water
(
SCIGROW
First
Index
Reservoir
Screening
Tool
(
FIRST),
Pesticide
Root
Zone
Model/
Exposure
Analysis
Modeling
System
(
PRZMS/
EXAMS),
and
monitoring
data.
If
monitoring
data
are
not
available
then
the
models
are
used
to
predict
potential
residues
in
surface
and
ground
water
and
the
highest
levels
(
whether
ground
or
surface)
are
assumed
to
be
the
drinking
water
residue.
In
the
case
of
pyrimethanil,
monitoring
data
are
not
available.
SCIGROW
and
FIRST
were
used
to
estimate
a
drinking
water
residue.
Calculation
of
the
Drinking
Water
Estimated
Concentration
(
DWEC)
for
surface
water
for
the
worst
case
pyrimethnail
use
scenario
results
in
a
acute
DWEC
of
122
ppb
and
a
chronic
DWEC
of
37
ppb.
Drinking
Water
Levels
of
Comparison
(
DWLOCs)
calculated
based
on
the
acute
and
chronic
risk
assessments
described
above
are
many
fold
higher
than
these
conservative
DWECs.
The
adult
acute
and
chronic
DWLOCs
are
9,860
ppb
and
5,936
ppb
respectively.
Children's
acute
and
chronic
DWLOCs
are
2,641ppb
and
1,686
ppb
respectively.
2.
Non­
dietary
exposure.
Pyrimethanil
products
are
not
labeled
for
residential
uses
(
food
or
non­
food),
thereby
eliminating
the
potential
for
residential
exposure
or
non­
occupational
exposure.

D.
Cumulative
Effects
Section
408(
b)(
2)(
D)(
v)
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.''
There
are
no
available
data
to
determine
whether
pyrimethanil
has
a
common
mechanism
of
toxicity
with
other
substances
or
how
to
include
this
pesticide
in
a
cumulative
risk
assessment.
Unlike
other
pesticides
for
which
EPA
has
followed
a
cumulative
risk
approach
based
on
a
common
mechanism
of
toxicity,
pyrimethanil
does
not
appear
to
form
a
toxic
metabolite
produced
by
other
substances.
For
the
purposes
of
the
tolerance
petition,
it
has
been
assumed
that
pyrimethanil
does
not
have
a
common
mechanism
of
toxicity
with
other
substances.

E.
Safety
Determination
1.
U.
S.
population.
Using
the
assumptions
and
data
described
above,
based
on
the
completeness
and
reliability
of
the
toxicity
data,
it
is
concluded
that
dietary
risk
from
the
proposed
uses
of
pyrimethanil
are
acceptable
for
all
populations
examined.
Chronic
exposure
for
the
U.
S.
population
utilizes
0.2%
(
0.000392
mg/
kg
bw/
day)
of
the
chronic
reference
dose.
Acute
exposure
for
the
U.
S.
population
utilizes
6.1%
(
0.018287
mg/
kg
bw/
day)
of
the
acute
reference
dose.
The
most
highly
exposed
population
of
non­
nursing
infants
utilizes
only
0.9%
of
the
chronic
reference
dose
and
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/
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68,
No.
31
/
Friday,
February
14,
2003
/
Notices
13.35%
of
the
acute
reference
dose.
The
actual
exposures
are
likely
to
be
much
less
as
more
realistic
data
and
models
are
developed.
EPA
generally
has
no
concern
for
exposures
below
100%
of
the
RfD
(
acute
or
chronic),
because
the
RfD
represents
the
level
at
or
below
which
exposure
will
not
pose
appreciable
risk
to
human
health.
DWLOC
for
adults
both
acute
(
9,860
ppb)
and
chronic
(
5,936
ppb)
are
several
orders
of
magnitude
above
the
conservative
DWEC
for
acute
(
122
ppb)
and
chronic
(
37
ppb)
worst
case
scenarios.
Therefore,
there
is
a
reasonable
certainty
that
no
harm
will
occur
to
the
U.
S.
population
from
aggregate
exposure
(
food
and
drinking
water)
to
residues
of
pyrimethanil.
2.
Infants
and
children.
The
relevant
toxicity
studies
as
discussed
in
the
toxicology
section
above
show
no
extra
sensitivity
of
infants
and
children
to
pyrimethanil,
therefore,
the
FQPA
safety
factor
can
be
removed.
Using
the
assumptions
and
data
described
in
the
exposure
section
above,
it
is
concluded
that
dietary
risk
from
the
proposed
uses
of
pyrimethanil
are
acceptable
for
all
infant
and
children
sub­
populations
examined.
The
most
highly
exposed
sub­
population
was
non­
nursing
infants
for
both
the
chronic
and
acute
analyses.
The
sub­
population
non­
nursing
infants
utilizes
0.9%
(
0.001563
mg/
kg
bw/
day)
of
the
chronic
reference
dose
and
13.35%
(
0.040040
mg/
kg
bw/
day)
of
the
acute
reference
dose.
All
other
infant
and
children
populations
have
less
exposure.
The
chronic
and
acute
drinking
water
levels
of
concern
for
children
(
1,684
ppb
and
2,600
ppb
respectively)
are
well
above
the
conservative
drinking
water
estimated
concentrations
for
chronic
and
acute
scenarios.
The
chronic
DWEC
is
37
ppb
and
the
acute
DWEC
is
122
ppb.
Therefore,
there
is
a
reasonable
certainty
that
no
harm
will
occur
to
infants
and
children
from
aggregate
exposure
to
residues
of
pyrimethanil.

F.
International
Tolerances
Maximum
Residue
Limits
for
pyrimethanil
have
not
been
established
by
the
Codex
Alimentarius
Commission.
[
FR
Doc.
03
 
3695
Filed
2
 
13
 
03;
8:
45
am]

BILLING
CODE
6560
 
50
 
S
ENVIRONMENTAL
PROTECTION
AGENCY
[
OPP
 
2003
 
0020;
FRL
 
7289
 
9]

Aspergillus
flavus
AF36;
Notice
of
Filing
a
Pesticide
Petition
to
Establish
an
Exemption
from
a
Tolerance
for
a
Certain
Pesticide
Microbial
Agent
in
or
on
Food
AGENCY:
Environmental
Protection
Agency
(
EPA).
ACTION:
Notice.

SUMMARY:
This
notice
announces
the
initial
filing
of
a
pesticide
petition
proposing
the
establishment
of
regulations
for
residues
of
a
certain
pesticide
microbial
agent
in
or
on
various
food
commodities.
DATES:
Comments,
identified
by
docket
ID
number
OPP
 
2003
 
0020,
must
be
received
on
or
before
March
17,
2003.
ADDRESSES:
Comments
may
be
submitted
electronically,
by
mail,
or
through
hand
delivery/
courier.
Follow
the
detailed
instructions
as
provided
in
Unit
I.
of
the
SUPPLEMENTARY
INFORMATION.

FOR
FURTHER
INFORMATION
CONTACT:
Shanaz
Bacchus,
Biopesticides
and
Pollution
Prevention
Division
(
7511C),
Office
of
Pesticide
Programs,
Environmental
Protection
Agency,
1200
Pennsylvania
Ave.,
NW.,
Washington,
DC
20460
 
0001;
telephone
number:
(
703)
308
 
8097;
e­
mail
address:
bacchus.
shanaz@
epa.
gov.

SUPPLEMENTARY
INFORMATION:

I.
General
Information
A.
Does
this
Action
Apply
to
Me?

You
may
be
potentially
affected
by
this
action
if
you
are
an
agricultural
producer,
food
manufacturer,
or
pesticide
manufacturer.
Potentially
affected
categories
and
entities
may
include,
but
are
not
limited
to:
 
Crop
production
(
NAICS
code
111)
 
Animal
production
(
NAICS
code
112)
 
Food
manufacturing
(
NAICS
code
311)
 
Pesticide
manufacturing
(
NAICS
code
32532)
This
listing
is
not
intended
to
be
exhaustive,
but
rather
provides
a
guide
for
readers
regarding
entities
likely
to
be
affected
by
this
action.
Other
types
of
entities
not
listed
in
this
unit
could
also
be
affected.
The
North
American
Industrial
Classification
System
(
NAICS)
codes
have
been
provided
to
assist
you
and
others
in
determining
whether
this
action
might
apply
to
certain
entities.
To
determine
whether
you
or
your
business
may
be
affected
by
this
action,
you
should
carefully
examine
the
applicability
provisions.
If
you
have
any
questions
regarding
the
applicability
of
this
action
to
a
particular
entity,
consult
the
person
listed
under
FOR
FURTHER
INFORMATION
CONTACT.

B.
How
Can
I
Get
Copies
of
this
Document
and
Other
Related
Information?
1.
Docket.
EPA
has
established
an
official
public
docket
for
this
action
under
docket
identification
(
ID)
number
OPP
 
2003
 
0020.
The
official
public
docket
consists
of
the
documents
specifically
referenced
in
this
action,
any
public
comments
received,
and
other
information
related
to
this
action.
Although
a
part
of
the
official
docket,
the
public
docket
does
not
include
Confidential
Business
Information
(
CBI)
or
other
information
whose
disclosure
is
restricted
by
statute.
The
official
public
docket
is
the
collection
of
materials
that
is
available
for
public
viewing
at
the
Public
Information
and
Records
Integrity
Branch
(
PIRIB),
Rm.
119,
Crystal
Mall
#
2,
1921
Jefferson
Davis
Hwy.,
Arlington,
VA.
This
docket
facility
is
open
from
8:
30
a.
m.
to
4
p.
m.,
Monday
through
Friday,
excluding
legal
holidays.
The
docket
telephone
number
is
(
703)
305
 
5805.
2.
Electronic
access.
You
may
access
this
Federal
Register
document
electronically
through
the
EPA
Internet
under
the
``
Federal
Register''
listings
at
http://
www.
epa.
gov/
fedrgstr/.
An
electronic
version
of
the
public
docket
is
available
through
EPA's
electronic
public
docket
and
comment
system,
EPA
Dockets.
You
may
use
EPA
Dockets
at
http://
www.
epa.
gov/
edocket/
to
submit
or
view
public
comments,
access
the
index
listing
of
the
contents
of
the
official
public
docket,
and
to
access
those
documents
in
the
public
docket
that
are
available
electronically.
Although
not
all
docket
materials
may
be
available
electronically,
you
may
still
access
any
of
the
publicly
available
docket
materials
through
the
docket
facility
identified
in
Unit
I.
B.
1.
Once
in
the
system,
select
``
search,''
then
key
in
the
appropriate
docket
ID
number.
Certain
types
of
information
will
not
be
placed
in
the
EPA
Dockets.
Information
claimed
as
CBI
and
other
information
whose
disclosure
is
restricted
by
statute,
which
is
not
included
in
the
official
public
docket,
will
not
be
available
for
public
viewing
in
EPA's
electronic
public
docket.
EPA's
policy
is
that
copyrighted
material
will
not
be
placed
in
EPA's
electronic
public
docket
but
will
be
available
only
in
printed,
paper
form
in
the
official
public
docket.
To
the
extent
feasible,
publicly
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