MEMORANDUM
Subject:
Residue
Chemistry
Science
Chapter
for
Zinc
2­
pyridinethiol­
1­
oxide
To:
Julie
Fairfax,
Product
Manager,
Team
36
Regulatory
Management
Branch
II
Antimicrobials
Division
(
7510C)

From:
A.
Najm
Shamim,
Ph.
D.,
Chemist
Risk
Assessment
and
Science
Support
Branch
Antimicrobials
Division
(
7510C)

Thru:
Kathryn
Montague,
Acting
Team
Leader,
Team
2
Risk
Assessment
and
Science
Support
Branch
Antimicrobials
Division
(
7510C)

And
Norm
Cook,
Branch
Chief
Risk
Assessment
and
Science
Support
Branch
Antimicrobials
Division
(
7510C)

DP
Barcode:
D251938
Chemical
Code:
088002
Submission:
S553943
Case:
2480
MRID
#:
441086­
02
Introduction:
Enclosed
is
the
Science
Chapter
on
Residue
Chemistry
for
Zinc
Omadine
in
support
of
the
Reregistration
Eligibility
Decision
(
RED).
Since
there
were
no
direct
food
uses
involved,
no
residue
chemistry
data
were
required
nor
submitted.
However,
this
chemical
was
approved
by
the
Food
and
Drug
Administration
(
FDA)
for
use
in
food
packaging
adhesives
(
indirect
food
contact)
for
which
the
registrant
submitted
a
migration
study.
Review
of
this
study
is
also
part
of
this
science
chapter.
The
relevant
references
are
attached
herewith.
1
ZINC
OMADINE:
RESIDUE
CHEMISTRY
SCIENCE
CHAPTER
Executive
Summary
Zinc
omadine
is
permitted
to
be
used
up
to
1000
ppm
level,
in
food
packaging
materials
and
repeat
use
polymeric
food
contact
materials.
In
addition,
it
is
also
used
in
laundry
products,
preservation
of
adhesives,
caulks,
patching
compounds,
sealants,
grouts,
latex
paints,
coatings,
dry
wall,
gypsum,
pearlite,
plaster,
styrene
butadiene
rubber,
thermoplastic
resins,
in­
can
preservation
of
clay,
mineral,
pigment
and
guar
slurries
and
in
latex
emulsions.
Results
from
laboratory
experiments
showed
that,
at
the
application
level
of
1000
ppm
in
food
packaging
materials
and
repeat
use
polymeric
materials,
the
migration
of
zinc
omadine
in
food
simulating
solvents
(
50%
alcohol/
water)
is
0.700
ppm.
This
represents
the
maximum
amount
of
zinc
omadine
migrating
out
from
the
polymeric
contact
surface.
The
Agency
has
completed
calculations
based
on
this
number
to
estimate
the
amount
of
migration
of
zinc
omadine
into
food
placed
on
a
conveyer
belt.
It
is
estimated
that
0.6733
ppb/
day
of
zinc
omadine
migrates
from
the
conveyer
belt
to
the
food.
The
migration
study
showed
that
zinc
omadine
migrates
from
the
conveyer
belt
at
this
level
for
the
first
five
days
and
then
declines.
Hence
the
maximum
migration
of
zinc
omadine
for
the
first
five
days
is
0.6733
ppb
x
5
=
3.3665
=
3.37
ppb.

A.
Chemical
Overview
Trade
Name:
Zinc
Omadine
Chemical
Name:
Zinc
2­
pyridinethiol­
1­
oxide
CAS
Registry
No.:
13463­
41­
7
OPP
Chemical
Code:
088002
Case
Number:
2480
Molecular
Formula:
Molecular
Weight:
340.00
Other
Chemical
Names:
Zinc
omadine,
zinc
1­
hydroxypyridine­
2­
thione,
zinc
pyridinethione,
zinc
2­
mercaptopyridine
N­
oxide,
zinc,
bis(
2­
pyridylthio)­
N,
N'­
dioxide,
zinc
pyrithione
B.
Use
Overview
The
products
containing
zinc
omadine
are
registered
for
uses
as
a
disinfectant
(
bacteriological/
germicidal),
bacteriostat,
fungicide,
microbicide/
microbiostat
(
slime
forming
fungi).
Use
sites
addressed
in
support
of
the
RED
include
food
packaging
adhesives
(
Indoor
food),
control
of
bacterial
growth
on
laundered
products
(
indoor
nonfood),
preservation
of
adhesives,
caulks,
patching
compounds,
sealants,
grouts,
latex
paints,
coatings,
dry
wall,
gypsum,
pearlite,
plaster.
Zinc
omadine
is
also
used
for
control
of
mildew
in
nonfood
contact
polymers
and
control
of
mildew
and
bacteria
in
styrene
butadiene
rubber
and
the
thermoplastic
resins.
In
addition,
use
extends
to
in
can
preservation
of
clay,
mineral,
pigment
and
2
guar
gum
slurries,
in
latex
emulsions
and
similar
high
solids
aqueous
media
.

RESIDUE
CHEMISTRYASSESSMENT:

I
Dietary
Exposure
and
Risk
Assessment
1.
Zinc
omadine
is
registered
by
the
Agency
for
use
in
food
packaging
adhesives
and
repeat
use
polymeric
food
contact
materials,
and
consequently
it
will
have
an
indirect
food
contact.
FDA
allowed
the
use
of
this
substance
in
adhesives
as
specified
under
21CFR
§
175.105(
a)
and
(
b)
at
a
maximum
level
of
1000
ppm,
at
temperatures
up
to
120o
F
(
49
o
C
)
and
subject
to
Good
Manufacturing
Practice.
(
FDA
Correspondence
to
Olin,
1995).
FDA
also
allowed
the
use
of
zinc
omadine
at
a
maximum
concentration
of
1000
ppm
(
one
pound
of
the
pesticide
per
thousand
pounds
of
food
packaging
materials)
in
repeat­
use
polyolefinic
foodcontact
materials
(
FDA
letter
to
Olin,
1994).
2
This
use,
however,
was
not
codified
under
CFR
21.
The
label
claim
for
zinc
omadine
powder
for
use
as
an
industrial
microbiostat
(
to
control
fungus)
is
at
a
level
of
750
to
1000
ppm
for
food
packaging
adhesives.
For
fungus
control
in
repeat­
use
polymeric
food
contact
materials,
the
use
level
is
at
1000
ppm
(
one
pound
per
thousand
pounds
of
polymer).

FDA
has
designed
a
`
Migration
Study'
which
recommends
that
registrants
render
data
for
Indirect
Food
Additive
Petitions
1.
EPA
does
not
have
corresponding
study
requirements
for
food
residues
resulting
from
the
`
migration'
of
pesticides
from
treated
adhesive
and
repeat­
use
polyolefinic
food
contact
materials.
The
Agency
has
determined
that
the
FDA
recommended
study
should
be
adequate
to
determine
the
residues
in
food.
Olin
submitted
(
1992)
a
Migration
/
Leach
Rate
Study
to
FDA
for
review.

The
Agency
has
decided
to
use
the
study
to
calculate
the
dietary
exposure
to
determine
if
there
are
any
toxicological
concerns
regarding
the
parent
or
the
transformation
products
(
MRID#:
441086­
02).
3
Summary
of
the
Study:

Two
solvents,
50%
ethanol,
which
simulates
alcoholic
food,
and
corn
oil
,
which
mimics
fatty
food
were
selected
for
the
migration
study.
Extractions
were
carried
out
at
49o
C
from
zero
to
10
days
from
the
zinc
omadine
treated
adhesive
at
the
use
level
and
the
repeat
polymeric
material
impregnated
with
zinc
omadine.
Each
sample
was
collected
in
triplicate.
These
extractions
were
analyzed
by
HPLC
technique.
Experiments
of
extraction
and
analysis
were
done
in
darkness
as
zinc
omadine
is
photosensitive.
Samples
with
4
times
the
allowed
level
of
pesticide
usage
(
4000
ppm)
were
also
analyzed
.
Polyethylene
and
polypropylene
were
used
as
the
polymers
impregnated
with
zinc
omadine.
Table
A
summarizes
the
migration
study
conducted
by
the
registrants:
3
Type
of
Polymer
Food
Simulant
Solvent
Zinc
Omadine
Level
In
The
Polymer1
Max.
Leached
From
The
Polymer
1,2,3
(
Migration),
M
Polyproplyene
Corn
Oil
1000
0.40
Polypropylene
Corn
Oil
4000
1.70
Polypropylene
50%
Ethanol/
Water
1000
0.04
Polypropylene
50%
Ethanol/
Water
4000
2.30
Polyethylene
Corn
Oil
1000
0.40
Polyethylene
Corn
Oil
4000
1.50
Polyethylene
50%
Ethanol/
Water
1000
0.70
Polyethylene
50%
Ethanol/
Water
4000
0.90
Notes:
1)
all
numbers
in
ppm;
2)
average
of
triplicate
analyses;
3)
all
experiments
were
conducted
at
49o
C
2.
Calculations
of
the
dietary
exposure
from
indirect
food
contact:

The
label
provided
by
the
registrant
lists
the
following
repeat­
use
polymeric
food
contact
materials:
food
processing
equipment,
conveyer
belts,
utensils,
storage
containers
to
which
zinc
omadine
is
applied
to
control
the
growth
of
fungus.
The
Agency
decided
to
use
conveyer
belt
as
representing
the
`
worst
case
scenario':
repeatability
of
use,
high
frequency
of
use
and
a
short
life
at
the
use
level.
The
registrant
provided
the
following
information
about
an
average
conveyer
belt,
treated
with
zinc
omadine:
4
1.
Average
life
of
use:
Two
years
2.
Average
length:
13
meters
3.
Average
width:
1.0
meter
4.
Impregnated
zinc
omadine:
1.4
kg/
m2
5.
Average
mass
of
the
belt:
18.2
kg
Based
on
the
information
provided
on
the
conveyer
belt
by
the
industry,
the
Agency
assumed
the
following
parameters
to
represent
the
`
worst
case
scenario':

Average
life:
Two
years
4
Average
length:
13
meters
Average
width;
1.0
meter
FDA
makes
the
following
assumption
to
estimate
the
dietary
exposure:

a.
Volume
to
surface
area
ratio
for
food
simulating
liquid
=
6.7
ml/
in2
b.
Amount
of
food
that
can
be
placed
in
1150
in2
=
8x106
g
Calculations:

length
x
width
=
13m
x
1m
=
13
m2...............
[
1]
=
13
m2
x
(
39.39
in)
2
/
m2
=
20386
in2
­­­­­­­­[
2]

Using
relation
a
and
eq.
2,
the
total
amount
of
food
that
can
be
put
on
the
conveyer
belt
at
one
time
is:
8
x
106
g
x
20386
in2
/
1150
in2
=
1.42
x
108
g
­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­[
3]

Assuming
the
conveyer
belt
is
made
up
of
polyethylene
type
of
material,
table
A
indicates
that
the
maximum
migration
from
the
polyethylene
material
into
the
FSL
(
50%
ethanol/
water):
=
0.70
ppm
­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­
[
4]

0.7
ppm
=
700
ppb
=
700
ng/
ml
of
zinc
omadine
migrating
­­­­­­­­­­­­­­­­­­­­­­­­­[
5]

Using
relation
a
and
equation
5:

Maximum
Migration
of
zinc
omadine
in
the
present
case:

=
700
ng
of
znOM/
ml
x
6.7
ml/
in2
=
4.69
µ
g/
in2
­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­[
6]

Using
equations
2,
3
and
6
to
obtain
the
maximum
migration
of
zinc
omadine
from
the
conveyer
belt
to
food
placed
on
it:

4.69
x10­
6
g/
in2
x
20386
in2
/
1.42
x
108
=
67331
x
10­
14
g­­­­­­­­­­­­­­­­­­­­[
7]

=
0.6733
ppb=
0.000673
ppm
­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­[
8]

Equation
8
represents
the
maximum
dietary
exposure
from
conveyer
belt
as
indirect
food
contact.

If
this
conveyer
belt
is
used
daily
for
260
days
/
per
year
(
taking
into
account
the
holidays),
then
the
total
migration
of
zinc
omadine
will
be:
5
0.6733
ppb/
day
x
260
days/
year
=
175.05
ppb
=
0.175
ppm
­­­­­­­­­­­­­­­­­­­­­­­­[
9]

The
migration
study
however,
shows
that
the
migration
of
zinc
omadine
from
the
conveyer
belt
to
the
food
maintains
this
level
up
to
five
days
and
thereafter
declines.
Hence
maximum
amount
of
zinc
omadine
migrates
out
from
the
conveyer
belt
is:

0.6733
ppb/
day
x
5
days
=
3.3665
ppb
=
3.37
ppb
=
0.00337
ppm=
0.0034
ppm
­­­[
10]

If
the
amount
of
zinc
omadine,
represented
in
eq.
8,
is
assumed
to
completely
(
100%)
migrate
from
the
conveyer
belt
into
the
food,
then
this
constitutes
the
worst
case
scenario.
Based
on
this
scenario,
the
Agency
has
calculated
the
estimated
daily
intake
(
EDI).
Assuming
an
average
adult
eats
3000
g
of
food/
day,
then
EDI
=
0.000673
ppm
­
0.000673mg/
kg
x
3
kg
food/
person/
day
=
0.0020
mg/
person/
day
­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­
[
11]

It
was
noted
by
the
Agency
that
the
third
recommended
food
simulant
solvent
namely
10%
ethanol
was
not
used
to
generate
the
migration
of
zinc
omadine
from
the
adhesives
or
repeat­
use
polymers.

The
registrant
used
the
HPLC
methods
to
quantitatively
estimate
the
migration
of
zinc
omadine
into
the
food
simulating
solvents.
It
has
been
recognized
by
registrants
that
under
a
controlled
study,
zinc
omadine
converts
to
omadine
disulfide,
omadine
sulfonic
acid
and
pyridine
sulfonic
acids.
No
data
were
made
available
to
the
Agency
about
the
residues
and
residue
concerns
of
these
transformation
products.

REFERENCES
1.
Recommendations
For
Chemistry
Data
For
Indirect
Food
Additive
Petitions
Chemistry
Review
Branch,
Office
of
Pre­
market
Approval,
Center
For
Food
Safety
&
Applied
Nutrition,
Food
&
Drug
Administration,
Washington,
DC
20204.
June
1995
2.
FDA
Letters
For
Indirect
Food
Contact:
FDA
Correspondence
With
Olin,
1994,
1995.

3.
EPA
MRID#:
441086­
02:
Study
Title:
FDA
Food
Contact
Approval
for
Zinc
Omadine:
Biocide
Leach
Rate
Study
(
Author:
George
Polson,
Nov.,
1992)
Study
submitted
by
Olin
Corporation
to
FDA.

4.
Data
provided
by
Arch
Chemicals
upon
Agency's
request,
October
27,2000
