Document ID: EPA-HQ-OPP-2005-0459-0005
Agency: epa
Document Type: Supporting & Related Material
Title: 
Posted Date: 2006-04-26T04:00Z

MEMORANDUM
Subject:
Imazalil
(
Chemical
111901,
Case
2325,
List
B):
Citrus
Oil
Food
Additive
Tolerance.
DP
Barcode
D220386.
CBRS
16424.
MRID
None.

From:
Stephen
Funk,
Chemist
Special
Review
Section
I
Chemistry
Branch
II
­
Reregistration
Support
Health
Effects
Division
(
7509C)

Through:
Edward
Zager,
Branch
Chief
Chemistry
Branch
II
­
Reregistration
Support
Health
Effects
Division
(
7509C)

To:
Niloufar
Nazmi
Special
Review
Branch
Special
Review
and
Reregistration
Division
(
7508W)

and
William
Hazel,
Ph.
D.
Risk
Characterization
and
Analysis
Branch
Health
Effects
Division
(
7509C)

Imazalil,
or
1­(
2­(
2,4­
dichlorophenyl)­
2­(
2­
propenyloxy)
ethyl)­
1Himidazole
is
a
fungicide
used
as
a
post­
harvest
treatment
for
citrus.
A
tolerance
of
10
ppm
has
been
established
for
the
combined
residues
of
imazalil
(
R
23979)
and
its
metabolite
1­(
2,4­
dichlorophenyl)­
2­(
1H­
imidazole­
1­
yl)­
1­
ethanol
(
R
14821)
in/
on
citrus
fruit
(
40
CFR
180.413(
a)).
A
food
additive
tolerance
of
25
ppm
exists
for
citrus
oil
(
40
CFR
185.3650),
and
a
feed
additive
tolerance
of
25
ppm
has
been
created
for
dried
citrus
pulp
(
40
CFR
186.3650).

A
review
of
grapefruit,
orange,
and
lemon
processing
studies
showed
that
imazalil
and
the
metabolite
R
14821
do
not
concentrate
in
juice,
but
do
concentrate
in
dried
pulp
(
1.7X
average
for
three
citrus
crops,
2.5X
maximum
average
based
on
oranges,
relative
to
the
unwashed
fruit)
and
in
oil
(
16X
average,
relative
to
unwashed
fruit).
The
existing
tolerance
for
dried
pulp
(
25
ppm)
was
considered
adequate,
but
the
existing
tolerance
for
oil
(
25
ppm)
was
found
unacceptable
(
S.
Funk,
CBRS
10563,
DP
D182575,
02/
17/
93).
CBRS
subsequently
recommended
for
a
new
food
additive
tolerance
of
150
ppm
for
the
combined
residue
of
imazalil
and
R14821
in
citrus
oil
(
FAP#
3H5680,
S.
Funk,
CBRS
12344,
D194053,
11/
02/
93).
The
issue
of
concentration
of
imazalil
and
its
metabolite
in
dried
citrus
pulp
was
previously
reconsidered
based
on
new
Agency
procedures
for
the
evaluation
of
processing
studies
and
the
determination
of
the
need
for
feed
additive
tolerances.
It
was
concluded
that
the
dilution
factor
exceeds
or
approximately
equals
2
the
concentration
factor
and
that
a
section
409
tolerance
was
not
needed
(
M.
Metzger
and
E.
Zager,
09/
13/
95,
Memorandum
to
Niloufar
Nazmi,
Special
Review
Branch).

The
registrant,
Janssen
Pharmaceutica,
has
requested
reconsideration
of
the
tolerance
requirement
for
citrus
oil.
The
registrant
contends
that
in
the
ready­
to­
eat
form
citrus
oil
contains
less
imazalil
residues
than
the
fresh
fruit.
Therefore,
the
registrant
is
petitioning
EPA
for
a
voluntary
revocation
of
the
food
additive
tolerance.
The
registrant's
position,
with
supporting
data,
is
stated
in
a
letter
and
attachment
from
William
Goodwine,
Manager,
Plant
Protection
Division,
04/
15/
95,
to
Daniel
Barolo.

Conclusion
and
Recommendation
CBRS
recommends
revocation
of
the
food
additive
tolerance
for
residues
of
imazalil
and
its
metabolite
in
citrus
oil.
The
dilution
factor
for
citrus
oil
(
238X)
in
its
conversion
to
a
readyto
eat
form
exceeds
the
average
concentration
factor
(
28X
based
on
oranges)
from
the
raw
agricultural
commodity
to
the
oil.

CBRS
further
recommends
establishment
of
a
Section
701
maximum
residue
limit
for
the
combined
residue
of
imazalil
and
R
14821
in
citrus
oil,
and
a
value
of
200
ppm
would
be
adequate
and
appropriate,
based
on
a
highest
average
field
residue
value
of
6.68
ppm
for
oranges
and
the
average
concentration
factor
(
28X)
for
orange
oil.
3
Detailed
Consideration
Field
Trial
and
Processing
Data
Summary
data
(
MRID
92072040;
92072030)
on
residues
of
imazalil
and
R14821
in/
on
citrus
from
postharvest
dip
treatment
were
submitted
in
Phase
4,
and
the
studies
were
found
acceptable
pending
a
storage
stability
study
(
S.
Funk,
Phase
4
Review,
10/
18/
90).
Janssen
Pharmaceutica
submitted
a
storage
stability
study
for
citrus
and
citrus
processed
commodities,
and
it
was
concluded
that
imazalil
and
R14821
are
stable
in
oranges,
orange
dried
peel,
orange
oil,
orange
molasses,
and
orange
juice
stored
frozen
for
up
to
34
weeks
(
S.
Funk,
CBRS
11335,
DP
D187775,
03/
02/
93).

The
results
of
trials
for
postharvest
treatment
of
citrus
with
imazalil
are
summarized
in
Table
1.
Only
trials
conducted
at
>
1X
the
registered
rate
are
included.
The
maximum
total
treatment
rate
for
packaging
and
storage
is
4000
ppm.
The
single
application
rate
varies
from
500
ppm
for
a
dip/
wash
to
2000
ppm
for
a
foamer,
packout
wax,
or
storage
wax.
Up
to
two
applications
may
be
made.
A
4000
ppm
wax
or
foamer
treatment
may
be
made
for
sporulation
control,
but
if
this
treatment
is
used,
no
additional
treatments
are
permitted.
This
use
information
was
obtained
from
the
following
labels:
EPA
registration
nos.
002792­
00049;
043813­
00006;
002792­
00051.

The
highest
average
field
trial
(
HAFT)
total
residue
from
treatment
at
a
total
rate
of
4000
ppm,
the
label
maximum,
is
6.68
ppm.

The
registrant
conducted
a
new
processing
study
for
purposes
of
reregistration,
and
the
processing
factors
for
that
study
are
summarized
in
Table
2
(
S.
Funk,
CBRS
10563,
DP
D182575,
02/
17/
93,
MRID
42454806).
The
concentration
factors
(
CF)
represent
the
concentration
of
total
imazalil
residue
in
the
conversion
of
treated,
unwashed
fruit
to
lemon,
orange,
and
grapefruit
oil.
4
Table
1:
Residues
of
Imazalil
and
R­
14821
In/
On
Citrus
Whole
Fruit
from
Postharvest
Treatment1
Crop/
Location
MRID
Treatment
Rate
(
ppm)
Days
Posttreatment
Imazalil
(
ppm)
R­
14821
Total
Imazalil
Equivalents2
(
ppm)

Orange/
FL
40509403
4000
wax
1
6.43
0.21
6.68
Grapefruit/
FL
40509403
4000
wax
1
5.07
0.15
5.25
Lemon/
CA
92072027
2000/
2000
storage
wax/
pack
wax
0
1.13
0.02
1.15
Lemon/
CA
92072027
2000/
2000
storage
wax/
pack
wax
0
0.84
0.07
0.92
Lemon/
CA
92072027
4000
pack
wax
0
1.60
0.17
1.80
Lemon/
CA
92072027
4000
pack
wax
0
1.45
0.13
1.60
Lemon/
CA
92072027
2000/
2000
storage
wax/
pack
wax
0
1.19
0.02
1.21
Orange/
CA
92072027
3320
pack
wax
0
1.38
0.15
1.56
Orange/
CA
92072027
6800
pack
wax
0
2.15
0.19
2.37
Orange/
FL
42454806
4000
storage
wax
0
3.46
<
0.05
3.52
Orange/
FL
42454806
8000
storage
wax
0
7.47
<
0.05
7.53
Lemon/
FL
42454806
2000/
4000
storage
wax/
pack
wax
0
7.21
0.364
7.64
Lemon/
FL
42454806
2000/
8000
storage
wax/
pack
wax
0
11.0
0.318
11.4
Grapefruit/
FL
42454806
4000
storage
wax
0
3.40
<
0.05
3.46
Grapefruit/
FL
42454806
8000
storage
wax
0
7.71
<
0.05
7.77
1
Includes
only
trials
where
total
treatment
rate
was
>
4000
ppm.
2
Factor
for
conversion
of
metabolite
to
imazalil
equivalents
is
MW
Imazalil/
MW
R
14821,
or
301
/
256
=
1.18.
5
Table
2:
Concentration
Factors
for
the
Conversion
of
Citrus
to
Citrus
Oil
Matrix
Concentration
Factor
Cold
Pressed
Lemon
Oil
4.11
2.51
3.3
Average
Cold
Pressed
Orange
Oil
241
331
28
Average
Cold
Pressed
Grapefruit
Oil
121
181
15
Average
Overall
Average
16
1
Average
of
3
determinations
for
RAC
and
oil.

The
average
processing
factor
for
three
citrus
crops
is
16X.
The
The
highest
average
processing
factor
is
28X
for
orange
oil.
Since
the
individual
oils
can
be
marketed,
e.
g.,
pure
orange
oil,
CBRS
concludes
that
residues
in
each
oil
should
be
calculated
separately.
The
HAFT
for
oranges
(
6.68)
multiplied
by
the
average
orange
processing
factor
(
28),
yields
a
maximum
residue
level
of
187
ppm
in
orange
oil.
Using
similar
considerations,
the
maximum
residue
levels
are
less
for
the
oils
of
lemons
and
grapefruit,
6.0
ppm
(
3.3
X
1.80
ppm)
and
79
ppm
(
15
X
5.25
ppm),
respectively.
Citrus
oils
are
not
considered
ready­
to­
eat
and
are
used
primarily
as
a
minor
ingredient
in
chewing
gums,
baked
goods,
gelatins,
and
puddings.
As
the
registrant
notes,
citrus
oils
in
the
concentrated
form
are
toxic
by
ingestion.
The
maximum
concentration
encountered
is
4200
ppm
in
chewing
gum
(
S.
Funk,
CBRS
15885,
D219490,
08/
28/
95).
The
dilution
factor
(
DF),
therefore,
is
238.
The
dilution
factor
(
238)
exceeds
the
average
concentration
factor
(
28)
by
a
factor
of
8.5.
As
consumed,
the
concentration
of
imazalil
and
its
metabolite,
expressed
as
imazalil
equivalents,
are
expected
to
be
less
than
the
concentration
in
the
raw
agricultural
commodity
(
whole
fruit).
For
example,
in
the
case
of
orange
oil,
the
maximum
residue
in
the
ready­
to­
eat
food
(
chewing
gum)
will
be
the
HAFT
X
CF/
DF
=
6.68
ppm
X
28
/
238
=
0.79
ppm,
which
is
well
below
the
Section
408
tolerance
of
10
ppm
for
citrus
fruit.
Therefore,
a
Section
409
tolerance
is
not
appropriate.
A
Section
701
Maximum
Residue
Limit
of
200
ppm
for
citrus
oils
is
needed
based
on
expected
residues
in
orange
oil.
6
cc:
Imazalil
List
B
File,
Imazalil
Subject
File,
RF,
circ.,
R.
Loranger,
K.
Davis
(
SRRD),
S.
Funk.

RDI:
A.
Rathman:
04/
30/
96:
R.
Loranger:
05/
02/
96:
E.
Zager:
05/
06/
96:

H7509C:
CBRS:
S.
Funk:
305­
5430:
CM#
2:
RM803:
SF(
0496.5):
04/
28/
96:
05/
07/
96.