Document ID: EPA-HQ-OPP-2006-0320-0012
Agency: epa
Document Type: Supporting & Related Material
Title: 
Posted Date: 2006-04-26T04:00Z

Page
1
of
9
UNITED
STATES
ENVIRONMENTAL
PROTECTION
AGENCY
WASHINGTON,
D.
C.
20460
OFFICE
OF
PREVENTION,
PESTICIDES
AND
TOXIC
SUBSTANCES
April
4,
2006
MEMORANDUM
DATE:
4/
04/
2006
SUBJECT:
2­(
Thiocyanomethylthio)
benzothiazole
Dietary
Assessment
for
the
Reregistration
Eligibility
Document
REVIEWER:
Robert
Quick,
Chemist
Risk
Assessment
&
Science
Support
Branch
Antimicrobials
Division
(
7510C)

THROUGH:
Norm
Cook,
Chief
Risk
Assessment
&
Science
Support
Branch
Antimicrobials
Division
(
7510C)

TO:
Kathryn
Avivah
Jakob,
Chemical
Review
Manager
Regulatory
Management
Branch
Antimicrobials
Division
(
7510C)

PC
CODES:
035603
DP
BARCODES:
D322616
Page
2
of
9
I.
Introduction
2­(
Thiocyanomethylthio)
benzothiazole
(
TCMTB)
Dietary
Exposure
The
Antimicrobials
Division
has
assessed
the
potential
antimicrobial
dietary
exposure
to
the
active
ingredient
2­(
Thiocyanomethylthio)
benzothiazole
(
TCMTB).
The
dietary
exposure
use
for
this
chemical
results
from
a
pulp
and
paper
use.

The
paper
uses
for
TCMTB
include
uses
as
a
slimicide,
a
wood
chip
use,
a
bacteriostatic
paper
use,
a
paper
adhesive
preservative
use
and
an
agricultural
mulch
paper
use.
The
registrant
stated
at
the
SMART
meeting
that
he
plans
to
cancel
the
wood
chip
use,
bacteriostatic
paper
use
and
the
agricultural
mulch
paper
use.
There
is
a
use
for
wood
treatment
but
the
registrant
states
that
the
use
is
not
intended
for
fruit
and
vegetable
packing
crates.

There
is
a
Food
&
Drug
Administration
(
FDA)
regulation
for
the
use
of
TCMTB
as
a
slimicide
(
21
CFR
176.300).

21
CFR
176.170
relates
to
"
Components
of
paper
and
paperboard
in
contact
with
aqueous
and
fatty
foods".
The
21
CFR
176.170
(
a)(
4)
states,
"
Substances
that
by
regulation
in
Parts
170
through
189
of
this
chapter
may
be
safely
used
without
extractives
limitations
as
components
of
the
uncoated
or
coated
surfaces
of
paper
or
paperboard
in
contact
with
aqueous
or
fatty
food,
subject
to
the
provisions
of
such
regulation".
Our
AD
interpretation
of
this
paragraph
(
personal
communication
between
Mr.
Dennis
Edwards,
RMB
I
Branch
Chief
and
Robert
Quick,
RASSB)
is
that
this
paragraph
would
also
permit
TCMTB
to
be
used
as
a
paper
coating
that
is
permitted
to
contact
aqueous
or
fatty
food.

2­(
Thiocyanomethylthio)
benzothiazole
(
TCMTB)
can
be
used
to
preserve
paper­
coating
formulations.
Several
labels
bear
paper
coating
uses
but
the
use
rate
for
application
to
the
coating
is
unclear.
Example:
EPA
Reg.#
1448­
37.
The
label
states:
"
Rate
of
application
will
vary
per
coating
rate."
The
registrant
must
clarify
the
labeling
to
show
the
label
rates(
ranges)
for
the
paper
coating
uses.

The
registrant
has
been
requested
by
the
CRM,
Kathryn
Avivah
Jakob,
to
clarify
the
use
pattern
for
coatings.
In
the
registrant's
latest
e­
mail
response
dated
12/
14/
2005,
the
registrant
states,
"
It
might
be
more
efficient
to
put
limitations
in
the
label
use
directions
in
which
text
is
added
stating
in
effect
of
`
Not
for
use
in
coatings
intended
for
food
contact'.
Will
this
suffice?"
AD
does
not
consider
label
restrictions
such
as,
"
Not
for
food
contact
use",
to
be
practical.
AD
would
consider
a
label
restriction(
s)
for
paper
that
defines
the
type
of
paper
that
is
to
be
treated;
e.
g.,
use
sites
such
as
wallboard
paper,
insulation
backing,
newsprint,
photographic
paper,
drawing
paper,
etc.
for
label
restrictions
that
preclude
food
contact
as
practical.
These
types
of
paper
are
not
likely
to
be
used
for
food
contact.
Page
3
of
9
The
registrant
could
also
revise
the
slimicide
use
on
the
labels
in
the
same
manner
that
AD
has
suggested
above
for
the
paper
coating
use;
i.
e.
define
the
type
of
paper
that
is
to
be
treated.
This
would
help
preclude
food
contact
with
TCMTB­
treated
paper.

There
are
agricultural
food
uses
for
TCMTB
which
are
for
seed
treatment
uses
to
a
variety
of
crops.
These
agricultural
food
uses
will
be
reviewed
by
the
Health
Effects
Division.

The
chemical,
2­
mercaptobenzothiazole,
is
the
main
mammalian
metabolite
of
TCMTB
(
Timothy
McMahon
memo
dated
12/
22/
2005).
This
chemical
and
its
sodium
and
potassium
salts
are
also
permitted
for
use
as
slimicides
by
the
Food
&
Drug
Administration
in
pulp
and
papermaking
(
21
CFR
176.300).
Residues
of
this
chemical
may
also
be
present
as
a
result
of
this
use
of
TCMTB
in
papermaking.
See
Other
Issues
below.

II.
Dietary
Exposure
for
TCMTB
Slimicide
Use
As
regulated
under
21CFR
176.300,
TCMTB
can
be
used
for
controlling
bacteria,
fungi
and
yeasts
which
cause
deterioration
of
paper
and
paperboard
products.
Dietary
exposure
to
TCMTB
as
a
slimicide
in
these
paper
mill
systems
were
estimated
using
the
following
assumptions:

 
The
slimicide
is
added
to
the
pulp
slurry
at
a
maximum
application
rate
of
2.0
lbs
of
slimicide
per
ton
of
dry
fiber
produced,
which
is
equivalent
to
1.2
lbs
of
TCMTB
per
2000
lbs
of
paper
(
EPA
Reg.
No.
1448­
37
is
60.0%
ai).
Since
there
is
no
control
over
how
the
paper
will
be
used
in
commerce,
AD
assumes
that
all
paper
can
contact
food
and
have
therefore
assessed
the
dietary
exposure
using
maximum
application
rate
which
comes
from
the
non­
food
use.
Since
paper
pulp
is
diluted
with
water
to
form
the
paper
slurry,
the
application
rate
must
be
adjusted
to
account
for
only
the
pulp/
paper
present
in
the
slurry.
Prior
to
entering
the
paper
machine,
the
paper
slurry
consists
of
less
than
1%
paper
pulp.
Therefore,
the
adjusted
application
rate
was
6.0
ppm
(
or
µ
g
ai/
g
pulp).
 
Prior
to
entering
the
driers,
the
slurry
consists
of
33%
pulp
and
67%
water.
The
application
rate
was
further
adjusted
to
account
for
the
amount
of
pulp
present
in
the
finished
paper.
 
The
finished
paper
(
after
paper
making)
contains
92%
pulp
and
8%
water.
 
The
standard
basis
weight
of
paper
is
50
mg/
in2.
 
The
amount
of
food
contacting
the
paper
packaging
is
10
g
of
food/
in2
of
paper.
 
The
consumption
factor
(
percentage
of
food
packaging
that
contacts
food)
is
10%.
 
There
is
100%
migration
of
TCMTB
from
the
treated
paper
into
food.
 
Adult
food
consumption
is
3
kg/
day;
child
food
consumption
is
1.5
kg/
day.
 
Adult
body
weight
is
70
kg
for
a
male;
60
kg
for
a
female
and
15
kg
for
a
child.
Page
4
of
9
Calculations:

Determination
of
the
application
rate
in
terms
of
ai
and
finished
paper
is:

Application
rate
on
label:
1.2
lbs
ai/
2000
lbs
of
finished
paper
Pulp
slurry
(
e.
g.,
water/
paper
pulp
mixture)
is
1%
pulp
therefore,
2000
lbs
paper/
0.01
=
200,000
lbs
of
slurry
1.2
lbs
ai/
200,000
lbs
of
slurry
=
6.0
ppm
of
ai
in
the
slurry
Conc.
of
ai
in
the
pulp
prior
to
entering
the
driers
is:
Adjusted
application
rate
x
water/
pulp
ratio
(
6.0
µ
g
ai/
g
slurry
water)
x
(
67
g
water/
33
g
pulp)
=
12.2
µ
g
ai/
g
pulp
Conc.
of
ai
in
the
finished
paper
is:
Adjusted
application
rate
x
percentage
of
pulp
in
finished
paper:
(
12.2
µ
g
ai/
g
pulp)
x
(
0.92
g
pulp
/
g
finished
paper)
=
11.2
µ
g
ai/
g
paper
Determination
of
dietary
concentration:
App
rate
x
Basis
paperweight
x
Surface
area
contacting
food
x
Consumption
factor
x
%
migration
(
11.2
µ
g
ai/
g
paper)
(
0.05
g
paper/
in2
paper)
(
in2
paper/
10
g
food)
(
0.1)
(
100%)
=
0.0056
µ
g
ai/
g
food
or
5.6
ppb
Determination
of
the
Estimated
Daily
Intake
(
EDI):
Dietary
conc.
x
Daily
food
consumption
Adult:
(
0.0056
µ
g
ai/
g
food)
(
3000
g
food
/
day)
=
16.8
µ
g
ai/
person/
day
Child:
(
0.0056
µ
g
ai/
g
food)
(
1500
g
food
/
day)
=
8.4
µ
g
ai/
person/
day
Determination
of
the
Daily
Dietary
Dose:
EDI
/
Body
Weight
Adult:
(
16.8
µ
g
ai
/
day)
(
mg/
1000
µ
g)
/
(
70
kg)
=
0.00024
mg
ai/
kg
bw/
day
Adult:
(
16.8
µ
g
ai
/
day)
(
mg/
1000
µ
g)
/
(
60
kg)
=
0.00028
mg
ai/
kg
bw/
day
Child:
(
8.4
µ
g
ai/
day)
(
mg/
1000
µ
g)
/
(
15
kg)
=
0.00056
mg
ai/
kg
bw/
day
Paper
Coating
Preservative
Use
The
label
use
appears
to
permit
the
use
of
coated
paper
for
both
dry
and
wet
food.

2­(
Thiocyanomethylthio)
benzothiazole
(
TCMTB)
can
be
used
to
preserve
paper­
coating
formulations.
Several
labels
bear
paper
coating
uses
but
the
use
rate
for
application
to
the
coating
is
unclear.
Example:
EPA
Reg.#
1448­
37.
The
label
states:
"
Rate
of
application
will
vary
per
coating
rate."
The
registrant
must
clarify
the
labeling
to
show
the
label
rates(
ranges)
for
the
paper
coating
uses.

In
the
case
of
EPA
Reg.
#
1448­
81,
label
directions
state:
"
To
inhibit
the
growth
of
bacteria
and
fungi
in
paper
making
additives
(
including
alum
solutions,
animal
glue
Page
5
of
9
solutions,
pigment
slurries,
coating
formulations,
and
starch
slurries
and
solutions)
Busan
1009
is
added
to
these
materials
in
concentrations
of
50­
400
ppm
(
weight/
weight)".
The
calculations
for
TCMTB
residues
in
the
paper
coating
and
in
food
are:

Dietary
exposures
to
TCMTB
from
this
formulation
were
estimated
using
the
following
assumptions:

 
The
preservative
is
added
to
paper
coating
formulations
at
a
maximum
application
rate
of
400
ppm,
which
is
equivalent
to
40
ppm
on
an
ai
basis
(
EPA
Reg.
No.
1448­
81
contains
10.0%
ai).

 
The
paper
coating
is
approximately
10%,
by
weight,
of
paper.

 
The
standard
basis
weight
of
paper
is
50
mg/
in2.

 
The
amount
of
food
contacting
the
paper
packaging
is
10
g
of
food/
in2
of
paper.

 
The
consumption
factor
(
CF)
(
percentage
of
daily
diet
expected
to
contact
paper
coatings)
is
20%.

 
There
is
100%
migration
of
TCMTB
from
the
treated
paper
into
food.

 
Adult
food
consumption
is
3
kg/
day;
child
food
consumption
is
1.5
kg/
day.

 
Adult
body
weight
is
70
kg
for
a
male
and
60
kg
for
a
female;
child
body
weight
is
15
kg.

In
the
case
of
EPA
Reg.#
1448­
81,
the
calculations
for
TCMTB
residues
in
the
paper
coating
and
in
food
are:

Calculations:

Determination
of
dietary
concentration:
App
rate
x
%
of
paper
that
is
coating
x
Basis
paperweight
x
Surface
area
contacting
food
x
Consumption
factor
x
%
migration
(
40
µ
g
ai/
g
coating)
(
0.10
g
coating/
g
paper)
(
0.05
g
paper/
in2
paper)
(
in2
paper/
10
g
food)
(
0.2)
=
0.004
µ
g
ai/
g
food
or
4.0
ppb
Determination
of
the
Estimated
Daily
Intake
(
EDI):
Dietary
conc.
x
Daily
food
consumption
Adult:
(
0.004
µ
g
ai/
g
food)
(
3000
g
food
/
day)
=
12.0
µ
g
ai/
person/
day
Child:
(
0.004
µ
g
ai/
g
food)
(
1500
g
food
/
day)
=
6.0
µ
g
ai/
person/
day
Determination
of
the
Daily
Dietary
Dose:
Page
6
of
9
EDI
/
Body
Weight
Adult:
(
12.0
µ
g
ai
/
day)
(
mg/
1000
µ
g)
/
(
70
kg)
=
0.00017
mg
ai/
kg
(
0.17ppb)
bw/
day
Adult:
(
12.0
µ
g
ai
/
day)
(
mg/
1000
µ
g)
/
(
60
kg)
=
0.0002
mg
ai/
kg
(
0.2
ppb)
bw/
day
Child:
(
6.0
µ
g
ai/
day)
(
mg/
1000
µ
g)
/
(
15
kg)
=
0.0004
mg
ai/
kg
(
0.4
ppb)
bw/
day
Paper
Adhesive
Preservative
Use
Several
labels
claim
that
TCMTB
can
be
used
to
preserve
paper­
adhesive
formulations.
However,
it
does
not
appear
that
this
use
has
been
cleared
by
the
US
FDA
under
21
CFR175.105.
Although
the
adhesive
use
has
not
been
officially
cleared
by
US
FDA,
it
was
included
in
this
assessment
in
order
to
determine
the
total
dietary
exposure
from
all
paper
uses.
Dietary
exposures
to
TCMTB
from
this
type
of
use
were
estimated
using
the
following
assumptions:

 
Based
on
FDA's
guidance
document,
it
was
assumed
that
a
chemical
used
as
"
an
adhesive
or
adhesive
component
in
accordance
with
the
limitations
of
21CFR175.105,
migration
levels
for
the
substance
generally
will
be
assumed
to
be
no
greater
that
50
ppb.
Applying
a
CF
(
consumption
factor)
of
0.14
for
adhesives
gives
a
dietary
concentration
of
7
ppb"
(
US
FDA,
2002).
Note:
CF
is
the
percentage
of
daily
diet
expected
to
contact
paper
adhesives.
 
Adult
food
consumption
is
3
kg/
day;
child
food
consumption
is
1.5
kg/
day.
Adult
body
weight
is
70
kg
for
a
male,
60
kg
for
a
female
and
for
a
child
15
kg.

Calculations:

Determination
of
the
Estimated
Daily
Intake
(
EDI):
Dietary
conc.
x
Daily
food
consumption
Adult:
(
0.007
µ
g
ai/
g
food)
(
3000
g
food
/
day)
=
21.0
µ
g
ai/
person/
day
Child:
(
0.007
µ
g
ai/
g
food)
(
1500
g
food
/
day)
=
10.5
µ
g
ai/
person/
day
Determination
of
the
Daily
Dietary
Dose:
EDI
/
Body
Weight
Adult:
(
21.0
µ
g
ai
/
day)
(
mg/
1000
µ
g)
/
(
70
kg)
=
0.00030
mg
ai/
kg
bw/
day
Adult:
(
21.0
µ
g
ai
/
day)
(
mg/
1000
µ
g)
/
(
60
kg)
=
0.00035
mg
ai/
kg
bw/
day
Child:
(
10.5
µ
g
ai/
day)
(
mg/
1000
µ
g)
/
(
15
kg)
=
0.0007
mg
ai/
kg
bw/
day
Page
7
of
9
TABLE
1
Cumulative
Estimated
Dietary
Intake
of
TCMTB
Use
Dietary
Conc.
(
ppb)
Estimated
Daily
Intake
(
µ
g/
person/
day)
Daily
Dietary
Dose
(
mg/
kg
bw/
day)
Pulp/
Paper
Slimicide
5.6
16.8
(
adult
M)
16.8
(
adult
F)
8.4(
child)
0.00024(
adult)
0.00028
(
adult)
0.00056
(
child)
Paper
Coating
Preservative
4
12
(
adult
M)
12
(
adult
F)
6
(
child)
0.00017
(
adult)
0.0002
(
adult)
0.0004
(
child)
Paper
Adhesive
Preservative
7
21
(
adult
M)
21
(
adult
F)
10.5
(
child)
0.00030
(
adult)
0.00035
(
adult)
0.0007
(
child)
Cumulative
16.6
49.8
(
adult)
24.9
(
child)
0.00071(
adult
M)
0.00083
(
adult
F)
0.0017
(
child)

Utilizing
the
acute
RfD
or
aPAD
of
0.25
mg/
kg
day
taken
from
the
Timothy
McMahon
memo
dated
12/
22/
2005,
the
dietary
risks
were
estimated
and
summarized
in
Table
2.

Utilizing
the
chronic
RfD
or
cPAD
of
0.013
mg/
kg
day
taken
from
the
Timothy
McMahon
memo,
the
dietary
risks
were
estimated
and
summarized
in
Table
2.
Page
8
of
9
TABLE
2
Dietary
Risks
of
TCMTB
USE
Daily
Dietary
Dose
(
mg/
kg
bw/
day)
%
aPAD
%
cPAD
Pulp/
Paper
Slimicide
0.00024
(
adult
M)
0.00028
(
adult
F)
0.00056
(
child)
0.096
(
adult
M)
0.11
(
adult
F)
0.22
(
child)
1.8
(
adult
M)
2.2
(
adult
F)
4.3
(
child)
Paper
Coating
Preservative
0.00017
(
adult
M)
0.0002
(
adult
F)
0.0004
(
child)
0.07
(
adult
M)
0.08
(
adult
F)
0.16
(
child)
1.31
(
adult
M)
1.54
(
adult
F)
3.08
(
child)
Paper
Adhesive
Preservative
0.00030
(
adult
M)
0.00035
(
adult
F)
0.0007
(
child)
0.12
(
adult
M)
0.14
(
adult
F)
0.28
(
child)
2.3
(
adult
M)
2.7
(
adult
F)
5.38
(
child)
Cumulative
0.00071
(
adult
M)
0.00083
(
adult
F)
0.0017
(
child)
0.29
(
adult
M)
0.33
(
adult
F)
0.66
(
child)
5.41
(
adult
M)
6.44
(
adult
F)
12.8
(
child)

Other
Issues
1.
The
chemical,
2­
mercaptobenzothiazole,
is
the
main
mammalian
metabolite
of
TCMTB
(
Timothy
McMahon
memo
dated
12/
22/
2005).
This
chemical
and
its
sodium
and
potassium
salts
are
also
permitted
for
use
as
slimicides
by
the
Food
&
Drug
Administration
in
pulp
and
papermaking
(
21
CFR
176.300).
Residues
of
this
chemical
may
also
be
present
as
a
result
of
this
use
of
TCMTB
in
papermaking.

The
registrant
must
address
the
question
of
whether
the
use
of
TCMTB
in
pulp
and
papermaking
will
result
in
residues
of
2­
mercaptobenzothiazole
in
paper
produced
using
TCMTB
and
provide
information
on
the
level
of
2­
mercaptobenzothiazole
that
will
occur
in
paper.

The
EPA
OPPIN
reference
does
not
show
any
active
registrations
for
2­
mercaptobenzothiazole.

2.
The
registrant
must
clarify
the
labeling
to
show
the
label
rates
(
ranges)
for
the
paper
coating
uses.

3.
In
the
registrant's
latest
e­
mail
response
dated
12/
14/
2005,
the
registrant
states,
"
It
might
be
more
efficient
to
put
limitations
in
the
label
use
directions
in
which
text
is
added
Page
9
of
9
stating
in
effect
of
`
Not
for
use
in
coatings
intended
for
food
contact'.
Will
this
suffice?"
AD
does
not
consider
label
restrictions
such
as,
"
Not
for
food
contact
use",
to
be
practical.
AD
would
consider
a
label
restriction(
s)
for
paper
that
defines
the
type
of
paper
that
is
to
be
treated;
e.
g.,
use
sites
such
as
wallboard
paper,
insulation
backing,
newsprint,
photographic
paper,
drawing
paper,
etc.
for
label
restrictions
that
preclude
food
contact
as
practical.
These
types
of
paper
are
not
likely
to
be
used
for
food
contact.

The
registrant
could
also
revise
the
slimicide
use
on
the
labels
in
the
same
manner
that
AD
has
suggested
above
for
the
paper
coating
use;
i.
e.
define
the
type
of
paper
that
is
to
be
treated.
This
would
help
preclude
food
contact
with
TCMTB­
treated
paper.