
Page
1
of
66
UNITED
STATES
ENVIRONMENTAL
PROTECTION
AGENCY
WASHINGTON,
D.
C.
20460
OFFICE
OF
PREVENTION,
PESTICIDES
AND
TOXIC
SUBSTANCES
Date:
April
19,
2006
MEMORANDUM
SUBJECT:
2­(
Thiocyanomethylthio)
benzothiazole
(
TCMTB)
Preliminary
Risk
Assessment
for
the
Reregistration
Eligibility
Decision
(
RED)
Document.
PC
Code:
035603.
Case
No.
2625.
DP
Barcode:
D322601
Regulatory
Action:
Reregistration
Eligibility
Decision
(
RED)
(
Phase
I)
Risk
Assessment
Type:
Single
Chemical
Aggregate
FROM:
Deborah
Smegal,
MPH,
Toxicologist/
Risk
Assessor
Samuel
Ary,
Chemist
Charles
Smith
Health
Effects
Division
(
HED)
(
7509C)

And
Siroos
Mostaghimi,
Ph.
D.
Environmental
Engineer
Robert
Quick,
Chemist
Kathryn
Montague,
M.
S.,
Biologist
Srinivas
Gowda,
Microbiologist/
Chemist
Chris
Jiang,
Chemist
Jonathan
Chen,
PhD.,
Toxicologist
Timothy
McMahon,
PhD.,
Toxicologist
Antimicrobials
Division
(
AD)
(
7510C)

And
James
Lin,
Environmental
Engineer
Environmental
Risk
Branch
1
Environmental
Fate
and
Effects
Division
(
7507C)
Page
2
of
66
THRU:
Phang
Whang,
Branch
Senior
Scientist
Reregistration
Branch
I
Health
Effects
Division
(
HED),
(
7509C)

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

Attached
is
the
Preliminary
Risk
Assessment
for
2­(
Thiocyanomethylthio)
benzothiazole
(
TCMTB)
for
the
purpose
of
issuing
a
Reregistration
Eligibility
Decision
(
RED).
The
disciplinary
science
chapters
and
other
supporting
documents
for
the
2­(
Thiocyanomethylthio)
benzothiazole
(
TCMTB)
RED
are
also
included
as
attachments
as
follows:

Toxicology
Disciplinary
Chapter
for
the
Re­
Registration
Eligibility
Decision
(
RED)
Risk
Assessment
for
2­(
thiocyanomethylthio)
benzothiazole
(
TCMTB).
D.
Smegal
April
4,
2006.
D328184
Occupational
and
Residential
Exposure
Assessment
for
2­(
Thiocyanomethylthio)
benzothiazole
(
TCMTB)
for
the
Reregistration
Eligibility
Decision
Document
(
RED)
(
Antimicrobial
Uses).
S.
Mostaghimi
.
April
19,
2006.
D322615
TCMTB
[
2­(
Thiocyanomethylthio)
benzothiazole]:
Occupational
and
Residential
Exposure
Assessment
for
the
Reregistration
Eligibility
Decision
Document
(
Agricultural
uses).
C.
Smith.
April
6,
2006.
D324014.
2­(
Thiocyanomethylthio)
benzothiazole
Dietary
Assessment
for
the
Reregistration
Eligibility
Document
(
Antimicrobial
uses).
R.
Quick.
April
4,
2006.
D322616
TCMTB:
Acute
and
Chronic
Dietary
Exposure
Assessments
for
the
Reregistration
Eligibility
Decision
(
Agricultural
uses).
S.
Ary.
February
28,
2006.
D324018.
TCMTB:
Summary
of
Analytical
Chemistry
and
Residue
Data
for
the
Reregistration
Eligibility
Decision
(
RED)
Document.
S.
Ary.
February
28,
2006.
D233617
Drinking
Water
Assessment
for
the
Use
of
the
Fungicide
of
2­(
Thiocyanomethylthio)
benzothiazole
(
TCMTB)
as
a
Seed
Treatment
on
Cotton,
Wheat,
Barley,
Oats,
Rice,
Sugar
Beets,
and
Safflower.
J.
Lin.
January
31,
2006.
D324010
2­(
Thiocyanomethylthio)
benzothiazole
(
TCMTB)
Ecological
Hazard
and
Environmental
Risk
Characterization
and
Environmental
Modeling
Chapters
for
the
Reregistration
Eligibility
Decision
(
RED)
Document
K.
Montague/
S.
Gowda/
S.
Mostaghimi.
D322613.
April
6,
2006.
Environmental
Fate
Assessment
of
2­(
Thiocyanomethylthio)
benzothiazole
(
TCMTB)
for
the
Reregistration
Eligibility
Decision
(
RED)
Document.
S.
Gowda,
March
30,
2006,
D319124
Product
Chemistry
Science
Chapter
for
2­(
Benzothiazolylthio)
methyl
thiocyanate.
Chris
Jiang,
Chemist,
November
17,
2005.
D322899.
Incident
Reports
Associated
with
2­(
Thiocyanomethylthio)
benzothiazole
(
TCMTB).
J.
Chen.
April
18,
2006.
D361478
Report
of
the
Antimicrobials
Division
Toxicity
Endpoint
Selection
Committee
(
ADTC)
for
2­(
Thiocyanomethylthio)
benzothiazole
(
TCMTB).
T.
McMahon,
April
19,
2006.
Page
3
of
66
1.0
EXECUTIVE
SUMMARY......................................................................................................................
4
2.0
INGREDIENT
PROFILE
......................................................................................................................
14
2.1
Summary
of
Registered/
Proposed
Food
Uses
.........................................................................
14
2.2
Structure
and
Nomenclature...................................................................................................
15
2.3
Physical
and
Chemical
Properties
..........................................................................................
15
3.0.
METABOLISM
ASSESSMENT............................................................................................................
16
3.1
Comparative
Metabolic
Profile
.................................................................................................
16
3.2
Nature
of
the
Residue
in
Foods
.................................................................................................
16
3.2.1
Description
of
Primary
Crop
Metabolism..........................................................................
16
3.2.2
Description
of
Livestock
Metabolism................................................................................
16
3.2.3
Description
of
Rotational
Crop
Metabolism,
including
identification
of
major
metabolites
and
specific
routes
of
biotransformation
...............................................................................................................
17
3.3
Environmental
Fate
...............................................................................................................
17
3.4
Tabular
Summary
of
Metabolites
and
Degradates
..................................................................
18
3.5
Toxicity
Profile
for
Major
Metabolites
and
Degradates
..........................................................
19
3.6
Summary
of
Residues
for
Tolerance
Expression
and
Risk
Assessment
...................................
19
4.0
HAZARD
CHARACTERIZATION.......................................................................................................
21
4.1
Hazard
Profile
for
TCMTB....................................................................................................
21
4.2
Hazard
Profile
for
2­
Mercaptobenzothiazole
(
2­
MBT)
...........................................................
25
4.3
FQPA
Considerations
............................................................................................................
27
4.4
Dose­
Response
Assessment
...................................................................................................
28
4.5
Endocrine
Disruption.............................................................................................................
30
5.0
PUBLIC
HEALTH
DATA.....................................................................................................................
30
6.0
EXPOSURE
ASSESSMENT
AND
CHARACTERIZATION.................................................................
32
6.1
Summary
of
Registered
Uses
.................................................................................................
32
6.2
Dietary
(
Food
and
Drinking
Water)
Exposure
and
Risk..........................................................
32
6.2.1
Residue
Profile
.................................................................................................................
33
6.2.2
Dietary
Exposure
for
Agricultural
Uses
.............................................................................
33
6.2.3
Dietary
Exposure
for
Antimicrobial
Uses
..........................................................................
35
6.3
Residential
Exposure/
Risk
Pathway.......................................................................................
37
6.3.1
Residential
Handler...........................................................................................................
37
6.3.2
Postapplication
Residential
Exposure
................................................................................
39
7.0
AGGREGATE
RISK
ASSESSMENTS
AND
RISK
CHARACTERIZATION........................................
41
8.0
CUMULATIVE
EXPOSURE
AND
RISK
.............................................................................................
43
9.0
OCCUPATIONAL
EXPOSURE
AND
RISK.........................................................................................
43
9.1
Agricultural
Uses
(
Seed
Treatment)
.......................................................................................
44
9.2
Antimicrobial
Uses................................................................................................................
46
10.0
ENVIRONMENTAL
RISK
...................................................................................................................
50
10.1
Environmental
Modeling/
Exposure........................................................................................
50
10.2.
Ecological
Toxicity
Data.
......................................................................................................
50
10.3
Bioaccumulation
in
Aquatic
Organisms.
................................................................................
54
10.4
Environmental
Exposure
Assessment.....................................................................................
55
10.5
Ecological
Risk
Characterization
...........................................................................................
56
10.6
Endangered
Species
Considerations
......................................................................................
58
11.0
DEFICIENCIES/
DATA
NEEDS............................................................................................................
59
12.0
REFERENCES......................................................................................................................................
62
4
1.0
EXECUTIVE
SUMMARY
2­(
Thiocyanomethylthio)
benzothiazole
(
TCMTB)
is
a
fungicide
used
in
commercial
and
on­
farm
seed
treatment
of
crops,
bulbs,
and
corn
as
well
as
treatment
of
flowers
and
seed
and
soil
treatment
of
trees.
TCMTB
has
23
tolerances
in
the
40
CFR
180.288
for
use
on
barley,
sugar
beets,
corn,
cotton,
oats,
rice,
safflower,
sorghum
and
wheat.
Use
on
sorghum
and
corn
are
no
longer
supported
by
the
registrants
and
thus
are
not
assessed
in
this
document.
TCMTB
food/
feed
end­
use
products
are
marketed
in
the
United
States
under
the
trade
names
Busan
®
,
Cotguard
®
,
Nusan
®
,
and
Nu­
Flow
®
.
The
Bayer
Cropscience
(
Bayer)
and
Wilbur­
Ellis
TCMTB
formulations
registered
for
food/
feed
uses
include
emulsifiable
concentrate
(
EC),
soluble
concentrate
(
SC)
and
suspo­
emulsion.
For
food/
feed
uses,
Bayer
is
supporting
TCMTB
use
on
cotton
only,
while
Wilbur­
Ellis
is
supporting
uses
on
barley,
oats,
rice,
wheat,
safflower,
cotton,
and
sugar
beets.
The
technical
registrant
of
TCMTB,
Buckman
Laboratories,
Inc.
(
Buckman)
has
requested
cancellation
of
all
food/
feed
uses.
Thus,
Bayer
and
Wilbur­
Ellis
will
be
responsible
for
providing
the
Agency
with
the
appropriate
data
needed
to
maintain
the
uses
on
their
product
labels.

As
an
antimicrobial
pesticide,
TCMTB
is
used
largely
as
a
wood
preservative
for
sapstain
control.
It
is
also
used
as
a
microbiocide/
microbiostat
and
bacteriocide/
bacteriostat
in
industrial
processes
and
water
systems,
as
well
as
in
industrial
materials
as
a
preservative.
It
is
a
slimicide
regulated
by
the
FDA
(
21
CFR
176.300)
for
controlling
bacteria,
fungi
and
yeasts
which
cause
deterioration
of
paper
and
paperboard
products.
It
is
also
used
as
a
paper
coating
preservative
and
paper
adhesive
preservative
use.
TCMTB
products
are
used
in
commercial/
institutional
premises,
residential
and
public
access
areas,
as
material
preservatives,
industrial
processes
and
water
systems,
and
as
wood
preservatives.
Examples
of
uses
include
use
in
pulp
and
paper
process
water,
use
for
sapstain
control,
use
as
a
preservative
for
leather
products
and
hides,
textiles,
paints,
adhesives,
wall
paper,
metal
working
fluids,
and
oil
recovery
drill
muds.
Products
containing
TCMTB
are
formulated
as
liquid
ready­
to­
use,
soluble
concentrate,
emulsifiable
liquid
and
suspo­
emulsion.
The
percentage
of
TCMTB
in
the
various
end­
use
products
ranges
from
1.0%
to
60%.

Hazard:
The
toxicology
data
base
for
TCMTB
is
considered
complete
for
a
food
use
pesticide.
No
additional
studies
are
required
at
this
time.
TCMTB
exhibits
low
acute
oral
and
dermal
toxicity
(
toxicity
category
III).
However,
it
is
highly
irritating
to
the
eyes
and
skin
(
toxicity
category
I
and
II,
respectively)
and
is
also
considered
to
be
highly
toxic
via
the
inhalation
route
of
exposure
(
toxicity
category
I).
TCMTB
is
a
dermal
sensitizer.

In
short­
term
rodent
studies,
TCMTB
appears
to
cause
portal
of
entry
effects.
It
caused
mild
to
severe
stomach
lesions
following
oral
exposure,
and
dose­
dependant
dermal
irritation,
ulcers,
hemorrhages,
chronic
dermatitis,
and
hematological
effects
following
dermal
exposure.
Decreased
body
weight
gain
and
food
consumption
were
also
noted
in
the
subchronic
oral
and
dermal
toxicity
studies.

In
developmental
toxicity
studies,
rabbits
appear
to
be
more
sensitive
to
the
toxicity
Page
5
of
66
of
TCMTB
than
rats,
based
on
maternal
toxicity.
No
adverse
developmental
effects
were
noted
in
rabbits
at
the
highest
dose
tested.
In
the
rat,
adverse
developmental
effects
were
observed
only
in
the
presence
of
maternal
toxicity.
These
effects
included
increased
fetal
and
litter
incidence
of
fused/
wavy
ribs,
rudimentary
cervical,
thoracic
and
lumbar
ribs
and
increased
incidence
of
sternebrae
and
pelvic
girdle
anomalies.

In
a
two­
generation
rat
reproduction
study,
there
were
no
treatment
related
effects
noted
at
the
highest
dose
tested
for
parental
toxicity
or
on
reproductive
parameters
examined
in
this
study.
Decreased
pup
weight
was
noted
only
in
the
F2B
pups
on
lactation
day
21.
This
finding
is
of
questionable
significance
because
the
pup
weight
was
not
significantly
reduced
at
days
7
or
14
in
the
F2B
pups,
and
there
were
no
consistent
effects
on
pup
weight
in
the
F0
and
F1a
generation
pups.

Dogs
appear
to
be
the
most
sensitive
species
to
TCMTB
toxicity
following
chronic
exposure.
In
the
chronic
dog
toxicity
study,
adverse
effects
were
noted
at
the
lowest
dose
tested
of
3.8
mg/
kg/
day.
Adverse
effects
included
decreased
body
weight
gain,
hematological
effects
(
changes
in
white
blood
cells,
monocytes),
alterations
in
clinical
chemistry
parameters
(
plasma
ALT)
and
decreased
uterine
weight
in
females.

In
the
chronic
rat
toxicity/
carcinogenicity
study,
no
adverse
effects
were
noted
at
the
highest
dose
tested
of
20
mg/
kg/
day.
However,
there
was
a
statistically
significant
increase
in
the
incidence
of
testicular
interstitial
cell
adenomas
in
males
of
mid­
and
high­
dose
levels
that
had
a
highly
significant
positive
dose­
related
trend.
Treatment
was
also
associated
with
a
possible
increased
incidence
of
thyroid
C­
cell
adenomas
in
females
of
the
mid­
and
high­
dose
levels,
which
had
a
highly
significant
positive
dose­
related
trend,
but
did
not
attain
a
statistically
significant
level
in
the
pairwise
comparison
with
concurrent
controls.

In
the
chronic
mouse
toxicity/
carcinogenicity
study,
decreased
body
weight
gain
was
noted
in
both
sexes,
while
there
was
a
statistically
increased
incidence
of
focal
and
diffuse
hyperplasia
of
duodenal
mucosa
in
males.
There
was
no
evidence
of
carcinogenicity.

TCMTB
was
negative
for
mutagenicity
in
the
gene
mutation
assay
with
bacteria,
and
did
not
cause
an
increase
in
unscheduled
DNA
synthesis
(
UDS)
in
rat
primary
hepatocytes
assay.
It
was
also
negative
for
chromosomal
aberrations
in
the
in
vivo
micronucleus
assay
in
mice.

Toxicity
Endpoints:
The
toxicity
endpoints
used
in
this
document
to
assess
potential
risks
include
acute
and
chronic
dietary
reference
doses
(
RfDs),
short­
term
incidental
oral,
and
short­,
intermediate­
and/
or
long­
term
dermal
and
inhalation
doses.
The
Antimicrobials
Division
Toxicity
Endpoint
Committee
(
ADTC)
selected
endpoints
in
September
2005
for
TCMTB.

Acute
and
Chronic
RfDs:
The
acute
RfD
is
0.25
mg/
kg/
day
using
a
no­
observable
effect
level
(
NOAEL)
of
25.1
mg/
kg/
day
for
all
populations
based
on
clinical
signs
of
Page
6
of
66
toxicity
(
ventral
alopecia,
rough
coat,
dyspnea/
wheezing,
oral
discharge,
diarrhea/
loose
stool,
urine
staining,
piloerection,
and
hunched
gait)
in
maternal
rats
in
the
rat
developmental
study.
The
chronic
RfD
is
0.013
mg/
kg/
day
for
all
populations,
using
a
LOAEL
of
3.8
mg/
kg/
day
based
on
a
chronic
dog
study
that
observed
decreased
body
weight
gain,
decreased
white
cells,
monocytes
and
plasma
ALT,
and
decreased
uterine
weight
in
females.
For
the
acute
RfD,
an
uncertainty
factor
of
100
(
10X
for
interspecies
extrapolation,
10X
for
intraspecies
variability)
was
applied
to
the
NOAEL.
For
the
chronic
RfD,
the
uncertainty
factor
is
300
(
10X
for
inter­
and
intra­
species
extrapolation,
and
3X
for
use
of
a
LOAEL).
The
Agency
recommended
that
the
Food
Quality
Protection
Act
Factor
(
FQPA)
safety
factor
be
removed
(
1X)
(
see
below).

Incidental
oral
endpoints:
The
short­
and
intermediate­
term
incidental
oral
NOAEL
is
16
mg/
kg/
day
based
on
decreased
body
weight
gain
and
food
consumption
in
maternal
animals
in
the
rabbit
developmental
study.
The
target
margin
of
exposure
(
MOE)
is
100
(
includes
10X
for
inter­
and
intra­
species
extrapolation
and
1X
FQPA
factor).

Dermal
endpoints:
The
short­
and
intermediate­
and
long­
term
dermal
NOAEL
is
25
mg/
kg/
day
from
a
dermal
study
based
on
decreased
body
weight
gain
and
food
consumption
in
males,
in
addition
to
significant
hematological
(
increased
neutrophils,
decreased
hemoglobin,
hematocrit
and
erythrocytes)
and
clinical
chemistry
changes
(
increased
urea
nitrogen,
glucose
and
globulins).
The
target
MOE
is
100
for
short­
and
intermediate­
term
durations
and
300
for
long
term
exposures
(
10X
for
inter­
and
intra­
species
extrapolation,
and
3X
for
subchronic
to
chronic
extrapolation).

Inhalation
endpoints:
The
short­
and
intermediate­
term
endpoint
is
based
on
an
oral
NOAEL
is
16
mg/
kg/
day
based
on
decreased
body
weight
gain
and
food
consumption
in
maternal
animals
in
the
rabbit
developmental
study.
The
long­
term
endpoint
is
based
on
a
LOAEL
of
3.8
mg/
kg/
day
an
oral
dog
study
that
observed
decreased
body
weight
gain,
decreased
white
cells,
monocytes
and
plasma
ALT,
and
decreased
uterine
weight
in
females.
Absorption
was
assumed
to
be
equivalent
between
oral
and
inhalation
exposure
(
i.
e.,
100%).
The
target
MOE
is
100
for
short­
and
intermediate­
term
durations
and
300
for
long­
term
durations
(
10X
for
inter­
and
intra­
species
extrapolation,
3X
for
use
of
a
LOAEL
for
chronic
duration,
and
includes
1X
FQPA
factor).
Because
the
inhalation
endpoints
are
based
on
oral
toxicity
data,
it
is
current
Agency
policy
for
antimicrobial
chemicals
to
require
an
inhalation
toxicity
study
if
the
estimated
inhalation
MOEs
are
below
a
MOE
of
1000.
Also,
the
acute
toxicity
data
suggest
that
TCMTB
is
more
toxic
via
the
inhalation
route
of
exposure
(
Toxicity
category
I)
relative
to
oral
exposure
(
Toxicity
category
III).

Cancer:
TCMTB
has
been
classified
as
Group
C
­
possible
human
carcinogen
­
and
the
Agency
recommended
that
for
the
purpose
of
risk
characterization,
the
Reference
Dose
(
RfD)
approach
be
used
for
quantitation
of
cancer
risk.
This
was
based
on
statistically
significant
increases
in
tumors
in
both
sexes
of
the
Sprague­
Dawley
rat:
testicular
interstitial
cell
adenomas
in
males
and
thyroid
c­
cell
adenomas
in
females.

FQPA
Safety
Factor.
The
ADTC
concluded
that
the
hazard
based
FQPA
safety
factor
should
be
removed
(
1X).
The
toxicology
data
base
is
complete
with
respect
to
assessing
the
increased
susceptibility
to
infants
and
children
as
required
by
FQPA
for
Page
7
of
66
TCMTB.
The
rat
and
rabbit
prenatal
developmental
studies
and
2­
generation
reproduction
study
showed
no
quantitative
or
qualitative
evidence
of
increased
susceptibility
(
i.
e.,
developmental/
offspring
NOAELs/
LOAELs
were
the
same
as
or
higher
than
those
for
maternal
effects).
In
addition,
there
were
no
effects
on
reproductive
parameters
in
the
2­
generation
reproductive
study.

Based
on
Agency
policy,
the
aRfD/
cRfD
modified
by
a
FQPA
safety
factor
is
a
population
adjusted
dose
(
PAD)
1.
The
Agency
calculated
an
acute
and
chronic
PAD,
and
uses
these
values
to
estimate
acute
and
chronic
dietary
risks,
respectively.

Dietary
(
Food
and
Drinking
Water)
Exposure
and
Risk:
The
Agency
has
conducted
a
dietary
exposure
and
risk
assessment
for
the
use
of
TCMTB
as
a
fungicide
for
seed
treatment
as
well
as
an
antimicrobial
pesticide
in
pulp
and
paper.
The
agricultural
seed
treatment
dietary
risks
include
both
food
and
drinking
water
exposures,
while
the
antimicrobial
dietary
risk
estimates
are
based
exclusively
on
potential
food
exposures.

When
assessing
chronic
(
non­
cancer)
dietary
risk,
the
Agency
considered
potential
dietary
exposure
to
the
U.
S.
population
including
infants
and
children,
as
well
as
to
females
of
childbearing
age
(
13­
50
years).
EPA
expresses
dietary
risk
estimates
as
a
percentage
of
the
aPAD
or
chronic
PAD.
Dietary
exposures
that
are
less
than
100%
of
the
aPAD
or
cPAD
are
below
the
Agency's
level
of
concern.

Agricultural
Uses.
For
the
seed
treatment
uses,
the
Agency
conducted
conservative
acute
and
chronic
dietary
exposure
assessments
that
incorporated
maximum
theoretical
concentration
factors
for
all
commodities,
existing
tolerance
level
residues,
100%
crop
treated,
and
the
FQPA
Index
Reservoir
Screening
Tool
(
FIRST)
estimated
drinking
water
concentrations.
For
the
acute
assessment,
the
FIRST
peak
concentration
was
used,
while
the
mean
concentration
was
used
in
the
chronic
assessment.
The
dietary
assessment
included
TCMTB
residues
in
plants
and
TCMTB
and
all
degradates,
including
2­
mercaptobenzothiazole
(
2­
MTB)
in
drinking
water.
The
acute
dietary
risk
estimates
do
not
exceed
the
Agency'
s
level
of
concern
(
less
than
100%
of
the
aPAD)
at
the
95th
exposure
percentile
for
the
U.
S.
population
(
less
than
1%
of
the
aPAD)
and
all
population
subgroups,
with
the
highest
exposed
population
subgroup
being
children
3­
5
years
old
at
2%
of
the
aPAD.
The
chronic
dietary
risk
estimates
do
not
exceed
the
Agency's
level
of
concern
(
less
than
100%
of
the
cPAD)
for
the
U.
S.
population
(
7%
of
the
cPAD)
and
all
population
subgroups,
with
the
highest
exposed
population
subgroup
being
children
3­
5
years
old
at
17%
of
the
cPAD.

Antimicrobial
Uses.
The
antimicrobial
uses
being
supported
are
expected
to
have
minimal
impacts
to
drinking
water.
The
registrants
intend
to
cancel
the
use
of
TCMTB
in
Reverse
Osmosis
Water
Systems,
and
Once
Through
Cooling
Towers,
while
the
wood
preservative
use
is
primarily
for
sapstain
control.
Thus,
the
dietary
risks
for
the
antimicrobial
uses
only
consider
potential
food
exposures.

1
PAD
=
Population
Adjusted
Dose
=
Acute
or
Chronic
RfD
FQPA
Safety
Factor
Page
8
of
66
In
the
absence
of
residue
data
for
TCMTB,
the
Agency
estimated
residue
levels
that
may
occur
in
food
that
could
contact
treated
pulp
and
paper
products
(
such
as
a
fast
food
wrapper),
from
the
maximum
application
rates
on
the
labels.
The
Agency
assessed
the
following
uses:
(
1)
pulp/
paper
slimicide
use;
(
2)
paper
coating
use;
and
(
3)
paper
adhesive
preservative
use.
In
addition,
the
Agency
estimated
a
total
cumulative
dietary
intake
of
TCMTB
that
could
result
from
simultaneous
exposure
from
all
three
uses.
The
Agency
used
an
FDA
model
to
estimate
the
Estimated
Daily
Intake
(
EDI),
along
with
a
number
of
conservative
assumptions.
In
the
absence
of
data,
the
daily
TCMTB
exposure
estimates
were
conservatively
used
to
assess
both
acute
and
chronic
dietary
risks.

The
acute
dietary
risk
estimates
are
below
the
Agency's
level
of
concern
for
all
population
subgroups.
The
highest
dietary
risk
estimate
is
0.66%
of
the
aPAD,
for
infants
and
children.
The
chronic
non­
cancer
dietary
analysis
indicates
all
risk
estimates
are
below
the
Agency's
level
of
concern
for
all
population
subgroups.
The
highest
dietary
risk
estimate
is
12.8%
of
the
cPAD,
for
infants
and
children.
It
is
possible
there
may
be
residues
of
concern
for
2­
mercaptobenzothiazole
(
2­
MBT),
which
is
the
main
mammalian
metabolite
of
TCMTB.
However,
the
Agency
does
not
have
reliable
information
at
this
time.
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).

Residential
(
Non­
Occupational)
Exposure
and
Risk:
TCMTB
is
an
antimicrobial
ingredient
used
as
a
material
preservative
in
residential
and
public
access
settings
in
textiles/
leather
products,
carpets
and
paints.
Residential
exposures
from
the
wood
preservative
use
are
expected
to
be
minimal
because
it
is
primarily
used
for
sapstain
control.
The
following
scenarios
were
considered
for
residential
handlers:
(
1)
painting
with
an
airless
sprayer,
and
(
2)
painting
with
a
brush/
roller.

The
Agency
also
evaluated
potential
postapplication
exposures
to
products
that
contain
TCMTB.
Postapplication
scenarios
evaluated,
which
were
considered
to
be
representative
of
all
possible
exposure
scenarios,
included:
(
1)
contact
with
treated
carpets
by
children
(
incidental
oral
and
dermal
exposure),
(
2)
dermal
contact
with
treated
textiles/
leather
products
by
adults
and
children,
and
(
3)
incidental
ingestion
of
treated
textiles/
blankets/
leather
products
by
children.
Duration
of
exposure
is
short­
term
(
1­
30
days)
and
intermediate­
term
(
1­
6
months)
for
all
residential
scenarios
assessed.
The
scenarios
were
evaluated
based
on
the
Residential
Exposure
Assessment
Standard
Operating
Procedures
(
SOPs),
product
label
maximum
application
rates,
related
use
information,
Agency
standard
assumptions,
inhalation
and
dermal
unit
exposure
data
from
the
Pesticide
Handlers
Exposure
Database
(
PHED).

Residential
Handler
Risk
Summary.
For
the
residential
handler
dermal
risk
assessment,
short­
and
intermediate­
term
risks
for
residents
that
could
apply
TCMTB­
treated
paint
were
of
risk
concern
(
MOEs=
10
and
25
for
airless
sprayer
and
paintbrush,
respectively
which
are
below
the
target
MOE
of
100).
The
inhalation
risk
estimates
were
not
of
concern
(
MOEs
were
above
the
target
MOE
of
100).
In
addition,
total
dermal
and
inhalation
risk
estimates
were
of
concern
primarily
because
of
the
dermal
Page
9
of
66
route
of
exposure.
These
risks
are
conservative
because
they
assume
an
individual
will
handle
15
gallons
of
paint
using
an
airless
sprayer
and
2
gallons
of
paint
via
paintbrush
in
one
day.

Postapplication
Residential
Risk
Summary.
For
the
residential
postapplication
scenarios
assessed
in
this
document,
risk
estimates
that
exceed
the
Agency's
level
of
concern
(
i.
e.,
dermal
and
incidental
oral
MOEs
<
100)
are:

°
Dermal
exposure
from
children
playing
on
a
treated
carpets
(
Dermal
MOE
=
2);
°
Dermal
exposure
from
children
wearing
treated
clothing/
leather
products
(
Dermal
MOE
=
<
1
with
a
100%
transfer
factor
and
Dermal
MOE
=
5.8
with
a
5%
transfer
factor);
°
Dermal
exposure
from
adults
wearing
treated
clothing
(
Dermal
MOE
<
1
with
a
100%
transfer
factor
and
Dermal
MOE=
9.1
with
a
5%
transfer
factor),
°
Incidental
oral
exposure
from
children
mouthing
treated
carpets
(
oral
MOE=
4.2),
and,
°
Incidental
oral
exposure
from
children
mouthing
treated
clothing/
leather
(
oral
MOE=
21).

As
noted
previously,
TCMTB
is
a
dermal
sensitizer.
Since
the
MOEs
are
based
on
systemic
effects
at
100
mg/
kg/
day,
the
Agency
intends
to
consider
the
potential
for
dermal
sensitization
in
recommended
labeling
language
of
pesticide
products
containing
TCMTB,
and
additional
dermal
toxicity
data
on
the
diluted
end­
use
formulations.

Aggregate
Exposure
and
Risk:
In
order
for
a
pesticide
registration
to
continue,
it
must
be
shown
that
the
use
does
not
result
in
"
unreasonable
adverse
effects
on
the
environment".
Section
2
(
bb)
of
FIFRA
defines
this
term
to
include
"
a
human
dietary
risk
from
residues
that
result
from
a
use
of
a
pesticide
in
or
on
any
food
inconsistent
with
standard
under
section
408..."
of
FFDCA.
As
mandated
by
the
FQPA
amendments
to
FIFRA
and
the
Federal
Food,
Drug
and
Cosmetic
Act
(
FFDCA),
the
Agency
must
consider
total
aggregate
exposure
from
food,
drinking
water
and
residential
sources
of
exposure
to
TCMTB.

The
Agency
conducted
both
acute
and
chronic
aggregate
assessments,
which
considered
food
and
drinking
water
exposures
from
the
registered
agricultural
and
antimicrobial
uses.
Because
there
are
no
long­
term
residential
exposures,
the
chronic
aggregate
assessment
only
considered
food
and
drinking
water.
Short­
and
intermediate­
term
aggregate
assessments
were
not
conducted
because
all
of
the
residential
uses
previously
evaluated
have
risks
of
concern
(
i.
e.,
handler
applying
paint,
children
playing
on
treated
carpets,
and
adults
and
children
wearing
treated
textiles/
leather
products).
Thus,
the
short­
and
intermediate­
term
aggregate
assessments
would
also
show
risks
of
concern.

Acute
Aggregate
Risk.
The
acute
aggregate
assessment
considers
the
95th
percentile
dietary
exposure
(
food
and
drinking
water)
from
the
agricultural
seed
treatment
uses,
as
well
as
the
acute
dietary
exposure
(
food
only)
from
the
antimicrobial
uses
in
pulp
Page
10
of
66
and
paper.
The
acute
dietary
aggregate
risk
is
2.5%
of
the
aPAD
for
children,
while
for
adults
it
is
1.3%
of
the
aPAD.
These
risk
estimates
are
below
the
Agency's
level
of
concern.

Chronic
Aggregate
Risk.
The
chronic
aggregate
assessment
considers
average
dietary
exposure
(
food
and
drinking
water)
from
the
agricultural
seed
treatment
uses,
as
well
as
dietary
exposure
(
food
only)
from
the
antimicrobial
uses
in
pulp
and
paper.
The
chronic
dietary
aggregate
risk
is
30%
of
the
cPAD
for
children,
while
for
adults
it
is
13.4%
of
the
cPAD.
These
risk
estimates
are
below
the
Agency's
level
of
concern.

Occupational
Exposure
and
Risk.
Occupational
handlers
can
be
exposed
to
TCMTB
in
a
variety
of
occupational
environments
based
on
its
agricultural
and
antimicrobial
use
patterns.
The
Agency
evaluated
representative
scenarios
using
maximum
application
rates
as
recommended
on
the
product
labels.
To
assess
the
handler
risks,
the
Agency
used
surrogate
unit
exposure
data
from
both
the
proprietary
Chemical
Manufacturers
Association
(
CMA)
antimicrobial
exposure
study
and
the
Pesticide
Handlers
Exposure
Database
(
PHED).
The
duration
of
exposure
is
expected
to
be
short­
or
intermediate­
term
(
1
day
to
6
months)
for
most
occupational
scenarios,
except
wood
preservation
and
metal
working
fluid
uses,
which
were
assumed
to
be
a
long­
term
exposure
duration.

Agricultural
Uses.
The
Agency
evaluated
occupational
risks
to
workers
that
use
TCMTB
as
a
fungicide
for
treating
seeds
in
commercial
and
on­
farm
settings.
For
commercial
seed
treatment,
all
individual
dermal
MOEs
met
or
exceeded
the
target
MOE
of
100
of
at
some
level
of
mitigation,
and
thus
are
not
of
concern.
However,
a
few
of
the
individual
inhalation
MOEs
did
not
meet
or
exceed
the
target
MOE
of
100.
Risks
remain
a
concern
for
3
scenarios
even
with
maximum
inhalation
risk
mitigation:

$
Multiple
activities
for
barley,
cotton,
oat,
rice,
safflower,
and
wheat
seeds.

For
commercial
seed
treatment,
most
of
combined
dermal
and
inhalation
risks
were
not
of
concern,
except
for
a
few
scenarios,
which
did
not
meet
the
target
MOE
of
100,
even
with
maximum
risk
mitigation.
Risks
remain
a
concern
for
4
scenarios
even
with
maximum
risk
mitigation:

$
Loader/
applicator
for
safflower;
and
$
Multiple
activities
for
barley,
cotton,
oat,
rice,
safflower,
and
wheat
seeds.

Postapplication
Exposure
and
Risk.
For
all
of
the
on­
nursery
seed
treatment
scenarios,
individual
dermal
and
inhalation
MOEs
met
or
exceeded
the
required
uncertainty
factor
of
100
at
some
level
of
risk
mitigation,
and
thus,
are
not
of
risk
concern.
For
on­
farm
seed
treatment
scenarios,
all
combined
dermal
and
inhalation
risks
met
or
exceeded
the
total
MOE
of
100
at
some
level
of
risk
mitigation
and
thus,
are
not
of
risk
concern.

Antimicrobial
Uses.
As
an
antimicrobial
pesticide,
TCMTB
is
used
in
commercial/
institutional
premises,
as
a
material
preservative,
in
industrial
processes
and
Page
11
of
66
water
systems,
and
as
a
wood
preservative.
Examples
of
registered
uses
include
use
in
pulp
and
paper
process
water,
use
for
sapstain
control,
use
as
a
preservative
for
leather
products
and
hides,
textiles,
paints,
adhesives,
wall
paper,
metal
working
fluids,
and
oil
recovery
drill
muds.
Additionally,
postapplication
exposures
are
likely
to
occur
in
these
settings
from
the
metal
working
fluid
use
and
wood
preservation
uses.

For
the
occupational
handlers,
dermal
and
inhalation
MOEs
were
above
the
target
MOE
of
100
for
short­
and
intermediate­
term
durations
at
either
single
layer
PPE
(
gloves)
for
open
pouring
or
through
the
use
of
mitigation
(
e.
g.,
metering
pumps)
for
all
scenarios
except
for
the
following
scenarios
listed
below.
It
should
be
noted
that
the
baseline
(
ungloved)
dermal
MOEs
for
material
preservation
of
paints,
textiles,
adhesives,
and
metalworking
fluid
were
calculated
using
unit
exposure
values
from
the
cooling
tower
CMA
data
set
because
baseline
dermal
unit
exposures
are
not
available
for
preservative
or
metal
fluid
categories.

 
Paint
Application
 
Airless
Sprayer:
ST/
IT
Dermal
MOE
=
6.1
(
ungloved)
and
17
(
gloved).
 
Paint
Application
 
Paintbrush:
ST/
IT
Dermal
MOE
=
30
(
ungloved)
and
97
(
gloved)
 
Paint
Preservation
 
Liquid
Pour:
ST/
IT
Dermal
MOE
=
1
(
ungloved)
 
Paint
Preservation
 
Liquid
Pump:
ST/
IT
Dermal
MOE
=
26
(
ungloved)
 
Textile
Preservation
 
Liquid
Pour:
ST/
IT
Dermal
MOE
=
<
1
(
ungloved)
 
Textile
Preservation
 
Liquid
Pump:
ST/
IT
Dermal
MOE
=
64
(
ungloved)
 
Cutting
Fluid
Preservation
 
Liquid
Pour:
ST/
IT
Dermal
MOE
=
11
(
ungloved)
 
Pulp
and
Paper
 
Liquid
Pump:
ST/
IT
Dermal
MOE
=
5
(
ungloved)

Many
of
these
MOEs
are
not
of
concern
with
the
addition
of
gloves
(
PPE).
The
total
dermal
and
inhalation
MOEs
with
PPE
(
gloves)
are
not
of
concern
for
the
majority
of
scenarios
evaluated.
The
total
MOEs
are
of
concern
(
i.
e.,
less
than
100)
for
the
following
exposure
scenarios:

 
Paint
Application
 
Airless
Sprayer:
MOE
=
16
 
Paint
Application
 
Paintbrush:
MOE
=
95
For
the
postapplication
assessment,
the
Agency
evaluated
exposures
to
TCMTB
from
metal
working
fluid
and
wood
preservative
use.
For
the
metal
working
fluid
scenario,
the
Agency
evaluated
both
dermal
and
inhalation
exposures
for
short­,
intermediate­
and
long­
term
exposure
durations.
Dermal
exposure
estimates
were
derived
using
the
2­
hand
immersion
model
from
ChemSTEER.
A
screening­
level
intermediate
and
long
term
inhalation
exposure
estimate
for
treated
cutting
fluids
has
been
developed
using
the
OSHA
PEL
for
oil
mist.
TCMTB
is
used
in
products
that
are
intended
to
preserve
wood
through
primarily
non­
pressure­
treatment
methods.
It
can
be
applied
as
a
sapstain
control
to
freshly­
cut
wood,
incorporated
into
particle
board,
or
used
to
treat
wood
chips.
When
used
as
a
sapstain
control,
the
product
may
be
dipped,
sprayed,
or
impregnated
into
the
wood
via
pressure
treatment
(
up
to
0.3%
a.
i.
solution).
When
used
in
particle
board,
the
pesticide
is
incorporated
into
the
resin
or
binding
agent
(
0.3%
a.
i.,
based
on
dry
weight
of
wood).
Page
12
of
66
For
the
occupational
postapplication
risk
assessment,
the
MOEs
were
above
target
MOE
of
100
for
short­
and
intermediate­
term
dermal
and
inhalation
exposures,
and
were
above
300
for
long­
term
durations,
and
therefore
not
of
concern
for
all
scenarios.

Environmental
Fate:
An
assessment
of
the
various
studies
indicates
the
hydrolysis
of
TCMTB
to
be
pH
dependent.
It
is
hydrolytically
stable
under
abiotic
and
buffered
conditions
at
pH
5
and
slowly
degrades
at
pH
7.
Under
more
alkaline
conditions,
hydrolysis
proceeds
more
rapidly
with
a
calculated
half­
life
ranging
from
1.8
to
2.1
days.
Photolytically,
TCMTB
degrades
in
a
pH
5
buffered
aqueous
solution
with
a
calculated
half­
life
of
1.5
hours.
Based
on
its
degradation,
TCMTB
may
not
pose
a
concern
for
surface
water
run­
off.

Aquatic
metabolism
under
aerobic
and
anaerobic
conditions,
as
well
as
aerobic
soil
metabolism,
is
a
major
route
of
dissipation
for
TCMTB.
TCMTB's
calculated
degradation
half­
life
in
flooded
lake
sediment
is
6.9
days;
however,
the
apparent
half­
life
occurs
between
2
and
4
days.
Similarly,
TCMTB
shows
a
tendency
of
degrading
anaerobically
in
flooded
sediment
within
2.7
days.
Under
aerobic
conditions
in
sandy
loam
soil,
a
representative
agricultural
soil,
TCMTB
degrades
with
a
calculated
half­
life
of
1.4
days.
Because
of
the
biodegradation
in
water
and
soils,
TCMTB
is
not
likely
to
contaminate
surface
and
ground
waters.

TCMTB's
tendency
to
bind
with
agricultural
soils
varies
according
to
soil
type.
TCMTB
is
very
mobile
in
clay
loam,
sand,
and
sandy
loam
soil,
and
mobile
in
clay
and
silt
loam
soil.
Kds
are
3.5
for
clay
loam
soil,
0.99
for
sand
soil,
9.9
for
sandy
loam
soil,
22.1
for
clay
soil,
and
62.7
for
silt
loam
soil.
There
may
be
a
water/
sediment
partitioning
issue
and
an
acute
adverse
impact
on
benthic
organisms.
However,
TCMTB
degrades
fairly
rapidly
in
freshwater
and
soils
and
the
impacts
may
be
short­
lived.

The
logKow
is
3.23
for
TCMTB,
which
indicates
a
potential
for
bioconcentration.
However,
the
results
of
a
bioconcentration
study
in
fish
indicate
that
bioaccumulation
of
TCMTB
will
be
minimal.
Maximum
bioconcentration
factors
(
BCFs)
measured
are
302
for
viscera,
64
for
fillet,
and
184
for
whole
fish
tissues.

Additional
information
on
the
aqueous
availability
of
TCMTB
from
wood,
indicates
that
the
use
of
TCMTB
as
a
wood
preservative
may
result
in
minimal
releases
to
the
environment.
Nevertheless,
the
Agency
conducted
modeling
to
estimate
TCMTB
concentrations
in
surface
water
from
the
antisapstain
use.
Based
on
conservative
assumptions,
the
Agency
estimated
runoff
concentrations
that
range
from
32.7
to
8.5
ppb.

Several
major
metabolites
are
formed
during
the
biotic
degradation
processes
of
TCMTB,
including
2­
benzothiazolesulfonic
acid
(
BTSA)
and
2­
mercaptobenzothiazole
(
2­
MBT).
BTSA
not
of
toxicological
concern
due
to
being
completely
excreted
(
sulfonic
acid)
and
having
negligible
toxicity.
2­
MBT
is
generally
less
toxic
than
parent
TCMTB;
therefore,
mitigation
of
any
risks
from
TCMTB
toxicity
endpoints
will
be
protective
of
any
risks
from
2­
MBT.
Therefore,
the
environmental
risk
assessment
was
conducted
for
Page
13
of
66
TCMTB
only.

Environmental
Hazard
and
Risk.
TCMTB
is
slightly
toxic
and
2­
MBT
is
practically
non­
toxic
to
birds
on
an
acute
oral
basis,
and
both
TCMTB
and
2­
MBT
are
slightly
toxic
to
birds
on
a
subacute
dietary
basis.
Based
on
the
results
of
mammalian
studies
conducted
to
meet
human
toxicity
data
requirements,
TCMTB
exhibits
low
acute
oral
and
dermal
toxicity
(
toxicity
category
III).
However,
it
is
highly
irritating
to
the
eyes
and
skin
(
toxicity
category
I
and
II,
respectively)
and
is
also
considered
to
be
highly
toxic
via
the
inhalation
route
of
exposure
(
toxicity
category
I).
The
NOAEL
determined
in
a
rat
2­
generation
reproduction
study
was
400
ppm.

Both
TCMTB
and
2­
MBT
are
very
highly
toxic
to
freshwater
fish
on
an
acute
basis.
Chronic
testing
indicates
that
TCMTB
causes
reproduction
and
growth
effects
in
fish
at
very
low
levels
(>
0.34
ppb).
TCMTB
is
very
highly
toxic
to
estuarine/
marine
fish
on
an
acute
basis.
TCMTB
is
very
highly
toxic
and
2­
MBT
is
moderately
toxic
to
freshwater
aquatic
invertebrates
on
an
acute
basis,
and
TCMTB
also
shows
very
high
acute
toxicity
to
marine/
estuarine
invertebrate
species.
TCMTB
impairs
growth
of
aquatic
vascular
plants
at
levels
greater
than
0.15
ppm
(
150
ppb).

Acute
risks
to
birds
and
mammals
from
consuming
TCMTB­
treated
seeds
were
below
Agency
Levels
of
Concern
(
LOCs).
Terrestrial
risks
from
the
wood
preservative
uses
of
TCMTB
were
not
addressed
due
to
a
lack
of
available
models
to
estimate
terrestrial
exposure
from
antisapstain
treatments.

Risks
to
aquatic
organisms
from
the
seed
treatment
use
of
TCMTB
are
below
the
Agency's
level
of
concern
(
LOCs).
However,
based
on
the
Tier
I
screening
model
used
for
the
antisapstain
use,
there
are
risks
to
aquatic
organisms.
Acute
LOCs
were
exceeded
for
all
taxa
except
aquatic
plants,
and
chronic
LOCs
for
fish
were
also
exceeded.
Chronic
risk
to
invertebrates
could
not
be
addressed
due
to
a
lack
of
chronic
toxicity
data.
An
environmental
monitoring
study
of
runoff
from
antisapstain
facilities
is
needed
to
address
the
potential
risks
of
concern
and
provide
estimated
environmental
concentrations
(
EEC)
to
use
in
a
refined
risk
assessment.
In
the
interim,
precautions
to
limit
leaching
and
runoff
from
antisapstain
treatment
facilities
areas
(
see
Label
Hazard
Statements
and
Use
Recommendations
section,
below)
should
prevent
exposure
to
aquatic
organisms.

Endangered
Species
Concerns:
There
are
potential
risks
to
Listed
Species
based
on
Tier
I
screening
modeling
for
the
antisapstain
wood
preservation
uses
of
TCMTB.
Since
the
model
is
only
intended
as
a
screening­
level
model,
and,
as
such,
has
inherent
uncertainties
and
limitations
which
may
result
in
inaccurate
exposure
estimations,
further
refinement
of
the
model
is
recommended
before
any
regulatory
action
is
taken
regarding
the
antisapstain
uses
of
TCMTB.
Additionally,
impacts
from
the
antisapstain
use
could
potentially
be
mitigated
with
precautions
to
prevent
leaching
and
runoff
when
wood
is
stored
outdoors.
Due
to
these
circumstances,
the
Agency
defers
making
a
determination
for
the
antisapstain
uses
of
TCMTB
until
additional
data
and
modeling
refinements
are
available.
At
that
time,
the
environmental
exposure
assessment
of
the
antisapstain
use
of
TCMTB
will
be
revised,
and
the
risks
to
Listed
Species
will
be
reconsidered.
Page
14
of
66
Data
Gaps/
Confirmatory
Data.
There
are
a
number
of
outstanding
data
requirements
for
TCMTB.
Because
there
are
inhalation
risks
of
concern
for
residential
and
occupational
use
patterns,
the
Agency
will
require
the
submission
of
a
subchronic
inhalation
toxicity
study.

Environmental
fate
data
that
are
required
to
support
the
wood
preservation
and
seed
treatment
uses
include:
hydrolysis
(
161­
1),
aerobic
soil
metabolism
(
162­
1),
anaerobic
soil
metabolism
(
162­
2)
and
aerobic
aquatic
metabolism
(
162­
3).
Additional
studies
are
held
in
reserve
pending
the
results
of
these
studies.

There
are
a
number
of
outstanding
ecological
data
requirements
for
TCMTB
for
the
wood
preservation
and
seed
treatment
uses
including
the
aquatic
invertebrate
life­
cycle
study
(
72­
4b/
850.1400),
the
Tier
II
seedling
emergence
and
vegetative
vigor
with
rice
(
123­
1/
850.4225
and
850.4250),
the
Tier
I
seedling
emergence
for
10
species
of
terrestrial
plant
(
122­
1/
850.4100)
and
the
Algal
Toxicity
study
(
123­
2/
850.5400).
In
addition,
the
Agency
requests
a
monitoring
study
of
runoff
from
antisapstain
facilities
to
establish
EEC's
for
risk
assessment.

The
following
Residue
Chemistry
Deficiencies
and
Regulatory
Guidelines
were
identified:
(
1)
Confirmatory
metabolism
data
should
be
submitted
depicting
the
nature
of
residues
in
wheat,
cotton,
and
sugar
beets;
(
2)
The
available
enforcement
method
(
Method
B
in
PAM
Vol.
II.)
is
outdated
and
uses
toxic
reagents;
therefore,
if
an
additional
method
that
is
adequate
for
tolerance
enforcement
is
available,
it
should
be
submitted
immediately
for
review;
(
3)
Storage
stability
data
were
not
included
with
the
original
field
trial
data
submissions;
therefore,
storage
stability
data
for
the
previously
submitted
field
trials
are
required
and
should
be
submitted
immediately;
and
(
4)
Additionally,
numerous
OPPTS
Guidelines
have
been
placed
on
reserve
pending
the
requested
plant
metabolism
data.

2.0
INGREDIENT
PROFILE
2.1
Summary
of
Registered/
Proposed
Food
Uses
Table
1.
Summary
of
Maximum
Application
Rates
for
Registered
TCMTB
Food/
Feed
Seed
Treatment
Uses
EPA
Reg.
No.
Product
Name
Formulation
Crop
Application
Equipment
Max.
App.
Rate
(
fl
oz/
100
lbs
of
seed)
Max.
App.
Rate
(
lbs
ai/
100
lbs
of
seed)
264­
965
Busan
®

30A
30%
EC
cotton
commercial
treater
4.5
fl
oz/
100
lbs
of
seed
0.093
lbs
a.
i./
100
lbs
of
seed
264­
983
Cotguard
®
5%
EC
cotton
commercial
treater
9.0
fl
oz/
100
lbs
of
seed
0.032
lbs
a.
i./
100
lbs
of
seed
cotton
commercial
treater
5.0
fl
oz/
100
lbs
of
seed
0.10
lbs
a.
i./
100
lbs
of
seed
barley,
oat,
rice,
wheat
commercial
treater
1.25
fl
oz/
100
lbs
of
seed
0.026
lbs
a.
i./
100
lbs
of
seed
2935­
389
Nusan
®
30
EC
30%
EC
safflower,
sugar
beet
commercial
treater
2.0
fl
oz/
100
lbs
of
seed
0.041
lbs
a.
i./
100
lbs
of
seed
commercial
treater
19.7
fl
oz/
100
lbs
of
seed
0.13
lbs
a.
i./
100
lbs
of
seed
2935­
413
Nu­
Flow
®

ND
9%
SC
cotton
on­
farm
treater
8.0
fl
oz/
100
lbs
of
seed
0.051
lbs
a.
i./
100
lbs
of
seed
Page
15
of
66
2.2
Structure
and
Nomenclature
Table
2.
TCMTB
Nomenclature.

Chemical
structure
N
S
S
S
N
Common
name
TCMTB
or
TCMB
Molecular
formula
C9H6N2S3
IUPAC
name
2­(
thiocyanomethylthio)
benzothiazole
CAS
name
(
2­
benzothiazolylthio)
methyl
thiocyanate
CAS
number
21564­
17­
0
PC
Code
035603
Supported
food/
feed
site
uses
barley,
cotton,
oat,
rice,
safflower,
sugar
beet,
and
wheat
End
Use
Products
Busan
®
30A,
Cotguard
®
,
Nusan
®
30
EC,
Nu­
Flow
®
ND
Synonyms
2­(
Benzothiazolylthio)
methyl
thiocyanate,
TCMTB,
TCMB,
Busan
72
Chemical
Class
Thiazole
2.3
Physical
and
Chemical
Properties
The
physical
and
chemical
properties
for
TCMTB
are
provided
in
Table
3.
The
product
chemistry
chapter
(
memo
from
C.
Jiang,
November
2005,
D322899)
provides
a
comprehensive
list
of
the
different
physical/
chemical
properties.

Table
3
Physical/
Chemical
Properties
of
TCMTB
Parameter
Value
Molecular
Weight
238
g/
mol
Henry
Law
Constant
atm.­
m3/
mol
Melting
Point
Not
applicable
for
liquids
Boiling
Point
Decomposed
at
191
oC
at
741.9
mm
Hg
Water
Solubility
45
mg/
L
log
Kow
3.23
at
20
oC
Vapor
Pressure
2.44
x
10­
10
mm
Hg
at
20
oC
4.04
x
10­
10
mm
Hg
at
25
oC
Physical
State
Liquid
Color
Vivid
orange
Odor
Strong,
sour
and
pungent
odor
(
like
mineral
oil)
Page
16
of
66
3.0.
METABOLISM
ASSESSMENT
3.1
Comparative
Metabolic
Profile
The
Risk
Assessment
Review
Committee
(
RARC)
met
and
determined
that
the
interim
residue
of
concern
for
tolerance
expression
and
risk
assessment
is
TCMTB
in/
on
plants
(
P.
Deschamp,
Report
of
the
RARC,
1/
11/
2006).
This
is
a
preliminary
decision
and
additional
confirmatory
metabolism
data
should
be
submitted
in
a
timely
manner.
For
drinking
water,
the
RARC
decided
that
the
residues
of
concern
for
risk
assessment
are
TCMTB
and
2­
MBT.

2­
Mercaptobenzothiazole
(
2­
MBT)
is
the
main
mammalian
urinary
metabolite
of
TCMTB,
and
has
been
suggested
as
a
biological
marker
of
exposure
to
TCMTB
(
Manninen
et
al.
1996).
2­
MBT
in
urine
is
a
suitable
indicator
of
workers'
exposure
to
TCMTB
when
a
sample
is
taken
immediately
after
a
work
shift.
In
animals,
the
urinary
excretion
of
2­
MBT
varies
by
administered
dose
level.
A
second
metabolite
was
2­(
mercaptomethylthio)
benzothiazole.
The
amount
of
2­
MBT
excreted
in
rat
urine
was
66
±
12%
(
SD),
51
±
20%
and
44
±
9%
for
TCMTB
doses
of
15,
75,
and
150
mg/
kg,
respectively.

3.2
Nature
of
the
Residue
in
Foods
3.2.1
Description
of
Primary
Crop
Metabolism
The
reregistration
requirements
for
plant
metabolism
have
not
been
fulfilled.
Data
have
been
submitted
depicting
the
uptake
of
TCMTB
in
corn,
cotton,
safflower,
and
wheat
and
were
found
to
be
inadequate
due
to
lack
of
identification
and/
or
characterization
of
parent
and/
or
metabolites.
Additional
metabolism
studies
conducted
with
tomatoes
and
melons
have
been
submitted
and
briefly
reviewed;
however,
translation
to
the
currently
registered
crops
is
not
adequate
for
reregistration
purposes.
Confirmatory
metabolism
data
should
be
submitted
depicting
the
nature
of
residues
in
wheat,
cotton,
and
sugar
beets.
Adequate
identification
and/
or
characterization
of
parent
and/
or
metabolites
should
be
conducted
as
required
by
OPPTS
860
Series
Guidelines.
The
Risk
Assessment
Review
Committee
(
RARC)
met
and
determined
that
the
interim
residue
of
concern
for
tolerance
expression
and
risk
assessment
is
TCMTB
in/
on
plants
(
P.
Deschamp,
Report
of
the
RARC,
1/
11/
2006).
This
is
a
preliminary
decision
and
additional
confirmatory
data
should
be
submitted
in
a
timely
manner.

3.2.2
Description
of
Livestock
Metabolism
No
livestock
metabolism
studies
have
been
submitted
for
review.
Livestock
metabolism
studies
may
be
required
if
the
requested
plant
metabolism
studies
show
uptake
of
residues.
Should
livestock
metabolism
studies
be
required,
the
registrant
must
provide
poultry
and
ruminant
metabolism
studies
following
OPPTS
860
Series
Guidelines.
Page
17
of
66
3.2.3
Description
of
Rotational
Crop
Metabolism,
including
identification
of
major
metabolites
and
specific
routes
of
biotransformation
No
confined
accumulation
data
in
rotational
crops
are
available;
however,
soil
persistence
studies
are
available.
With
the
exception
of
storage
stability
and
method
data
that
were
not
submitted
with
the
original
studies,
soil
persistence
is
not
likely
to
be
a
concern
with
respect
to
follow­
up
crops.

3.3
Environmental
Fate
Detailed
information
on
environmental
fate
is
presented
in
the
attached
memo
from
S.
Gowda
(
March
30,
2006,
D319124).
A
brief
summary
is
provided
below.

An
assessment
of
the
various
studies
indicates
the
hydrolysis
of
TCMTB
to
be
pH
dependent.
It
is
hydrolytically
stable
under
abiotic
and
buffered
conditions
at
pH
5
and
slowly
degrades
at
pH
7.
Under
more
alkaline
conditions,
hydrolysis
proceeds
more
rapidly
with
a
calculated
half­
life
ranging
from
1.8
to
2.1
days.
Photolytically,
TCMTB
degrades
in
a
pH
5
buffered
aqueous
solution
with
a
calculated
half­
life
of
1.5
hours.
Based
on
its
degradation,
TCMTB
may
not
pose
a
concern
for
surface
water
run­
off.

Aquatic
metabolism
under
aerobic
and
anaerobic
conditions,
as
well
as
aerobic
soil
metabolism,
is
a
major
route
of
dissipation
for
TCMTB.
TCMTB's
calculated
degradation
half­
life
in
flooded
lake
sediment
is
6.9
days.
Similarly,
TCMTB
shows
a
tendency
of
degrading
anaerobically
in
flooded
sediment
within
2.7
days.
Under
aerobic
conditions
in
sandy
loam
soil,
a
representative
agricultural
soil,
TCMTB
degrades
with
a
calculated
half­
life
of
1.4
days.
Because
of
the
biodegradation
in
water
and
soils,
TCMTB
is
not
likely
to
contaminate
surface
and
ground
waters.

TCMTB's
tendency
to
bind
with
agricultural
soils
varies
according
to
soil
type.
TCMTB
is
very
mobile
in
clay
loam,
sand,
and
sandy
loam
soil,
and
mobile
in
clay
and
silt
loam
soil.
Kds
are
3.5
for
clay
loam
soil,
0.99
for
sand
soil,
9.9
for
sandy
loam
soil,
22.1
for
clay
soil,
and
62.7
for
silt
loam
soil.
There
may
be
a
water/
sediment
partitioning
issue
and
an
acute
adverse
impact
on
benthic
organisms.
However,
TCMTB
degrades
fairly
rapidly
in
freshwater
and
soils
and
the
impacts
may
be
short­
lived.

The
bioaccumulation
of
TCMTB
in
freshwater
fish
assumed
to
be
minimal
if
any.
Maximum
bioconcentration
factors
(
BCFs)
measured
are
302
for
viscera,
64
for
fillet,
and
184
for
whole
fish
tissues.

Additional
information
on
the
aqueous
availability
of
TCMTB
from
wood,
indicates
that
the
use
of
TCMTB
as
a
wood
preservative
may
result
in
minimal
releases
to
the
environment.

The
two
main
degradates
of
TCMTB
observed
in
laboratory
tests
were
2­
mercaptobenzothiazole
(
2­
MBT)
and
benzothiazol
sulfonic
acid
(
BTSA).
However,
most
of
the
environmental
fate
laboratory
studies
were
not
carried
out
long
enough
to
allow
Page
18
of
66
a
quantitative
discussion
of
the
amount
of
these
degradates
that
might
be
formed
in
the
environment.
For
instance,
the
maximum
amount
of
2­
MBT
observed
in
the
aerobic
aquatic
metabolism
study
was
23.6%
of
applied
radioactivity.
Since
this
was
observed
on
the
31st
and
final
day
of
the
study,
though,
a
complete
description
of
the
formation
and
decline
of
this
degradates
is
not
possible.
MBT
has
several
industrial
uses.

3.4
Tabular
Summary
of
Metabolites
and
Degradates
Table
4.
Chemical
Names,
Metabolism
Data,
and
Structures
of
TCMTB
and
Its
Metabolites/
Degradates
Percent
TRR1
Chemical
Name
Commodity
Major
Residue
(>
10%
TRR)
Minor
Residue
(<
10%
TRR)
Structure
Melon
fruit
ND2
Melon
plant
0.9%

Tomato
fruit
ND
Tomato
plant
ND
TCMTB
[
2­
benzothiazolylthio)
methyl
thiocyanate]
CAS
number:
21564­
17­
0
Aerobic
soil
(
58
DPT3)
0.6%
N
S
S
S
N
Melon
fruit
31.9%

Melon
plant
14.0%

Tomato
fruit
61.7%

Tomato
plant
32.6%
2­
BTSA
[
2­
benzothiazolesulfonic
acid]

Aerobic
soil
(
58
DPT)
70.8%
N
S
SO
3
H
Melon
fruit
8.4%

Melon
plant
2.6%

Tomato
fruit
8.5%
OH­
2­
BTSA4,5
[
2­(
hydroxybenzothiazolyl)
sulfonic
acid]

Tomato
plant
21.2%
N
S
SO
3
H
O
H
Melon
fruit
1.3%

Melon
plant
2.5%

Tomato
fruit
ND
Tomato
plant
ND
2­
OH­
BT
[
2­
hydroxybenzothiazole]
or
BTOL
[
2­
benzothiazolol]
CAS
number:
934­
34­
9
Aerobic
soil
(
21
DPT)
7.0%
N
S
OH
Melon
fruit
0.7%

Melon
plant
0.1%

Tomato
fruit
ND
Tomato
plant
ND
Cotton
forage
ND
Aerobic
soil
(
1.5
DPT)
30.3%
2­
MBT
or
2­
SH­
BT
[
2­
mercaptobenzothiazole]
CAS
number:
149­
30­
4
Aerobic
soil
(
14­
21
DPT)
0.3­
0.4%
N
S
SH
Page
19
of
66
2,2'­
DTBB
or
DBB
[
2,2'­
dithiobis(
benzothiazole)
CAS
number:
120­
78­
5
Aerobic
soil
(
maximum
at
1
DPT)
6.7%

N
S
S
S
N
S
1.
TRR
=
Total
radioactive
residue.
2.
ND
=
Not
detected.
3.
DPT
=
Days
post­
treatment.
4.
Two
isomers
make
up
2­(
hydroxybenzothiazolyl)
sulfonic
acid.
The
exact
position
of
the
hydroxyl
group
was
not
determined.
The
numbers
presented
in
the
table
are
the
summation
of
the
two
isomers.
The
following
sentence
is
the
breakdown
of
TRR
for
each
isomer
and
is
in
the
parenthesis
following
each
individual
commodity.
Melon
fruit:
8.4%
(
1.1%
and
7.3%),
melon
plant:
2.6%
(
1.4%
and
1.2%),
tomato
fruit:
8.5%
(
6.9%
and
1.6%),
and
tomato
plant:
21.2%
(
6.7%
and
14.5%).

3.5
Toxicity
Profile
for
Major
Metabolites
and
Degradates
The
primary
urinary
metabolite
is
2­
MBT.
The
toxicity
database
for
2­
MBT
is
extensive
because
this
chemical
was
formally
a
registered
pesticide.
However,
there
are
no
longer
any
registered
uses
for
2­
MBT.
See
Section
4.2
for
a
detailed
discussion
of
the
hazard
profile
of
2­
MBT.

3.6
Summary
of
Residues
for
Tolerance
Expression
and
Risk
Assessment
The
Health
Effects
Division
(
HED)
Risk
Assessment
Review
Committee
(
RARC)
met
and
determined
that
the
residue
of
concern
for
tolerance
expression
and
risk
assessment
is
TCMTB
in/
on
plants.
This
decision
is
considered
preliminary
pending
the
results
of
the
outstanding
metabolism
studies
that
are
required
to
support
the
currently
registered
uses.
For
drinking
water,
the
RARC
decided
that
the
residues
of
concern
for
risk
assessment
are
TCMTB
and
2­
MBT.
Summary
of
the
decisions
concerning
the
residues
of
concern
in
plants
and
drinking
water
are
presented
below
in
Table
5.

Table
5.
Summary
of
TCMTB
Residues
to
be
Included
in
the
Risk
Assessment
and
Tolerance
Expression
Matrix
Residues
Included
in
Risk
Assessment
Residues
Included
in
Tolerance
Expression
Primary
crop
­
barley,
cotton,
oat,
rice,
safflower,
sugar
beet,
and
wheat
TCMTB
TCMTB
Plants
Rotational
crop
NA
=
not
applicable
NA
Ruminant
NA
NA
Livestock
Poultry
NA
NA
Drinking
water
TCMTB
and
2­
MBT
NA
NA=
Not
applicable
The
determination
of
the
residues
of
concern
in
plant
commodities
is
based
on
the
tomato
and
melon
metabolism
studies
and
the
available
toxicity
data.
2­
BTSA
was
found
Page
20
of
66
at
significant
levels
(
62%
in
tomato
fruit);
however,
it
should
be
excluded
as
a
residue
of
concern
because
it
is
expected
to
be
less
toxic
than
the
parent
TCMTB.
2­
BTSA
is
likely
to
not
contribute
significantly
to
the
chronic
toxicity
of
the
parent
based
on
the
following
considerations:

1.
2­
BTSA
is
a
very
polar
structure
lacking
the
structural
features
of
the
parent
(
TCMTB)
that
might
lead
to
toxicologically
significant
species.
Although
the
mode
of
toxic
action
of
the
parent
is
not
known,
its
thiocyanomethylthio
moiety
is
likely
to
be
metabolized
to
toxic
species.
This
group
is
not
present
in
2­
BTSA.
Thus,
2­
BTSA
cannot
contribute
to
toxicity
via
this
group.

2.
If
the
benzimidazole
ring
of
TCMTB
is
involved
in
its
toxic
effects
by
biotransformation
to
electrophilic
species,
2­
BTSA
is
not
likely
to
undergo
this
type
of
biotransformation.
2­
BTSA,
being
a
sulfonic
acid,
is
expected
to
undergo
little
or
no
metabolism.
Small
molecule­
sulfonic
acids
generally
undergo
little
or
no
biotransformation.
For
example,
methanesulfonic,
benzenesulfonic,
and
naphthylaminesulfonic
acids
are
excreted
untransformed
in
laboratory
animals
(
Biological
Basis
of
Detoxication,
Caldwell
J.
&
Jakoby
W.
B.
[
eds],
1984,
p.
162).

3.
In
a
chemical
with
a
mercapto
group
(­
SH),
oxidation
of
the
mercapto
group
to
the
corresponding
sulfonic
acid
is
known
to
produce
a
marked
decrease
in
toxicity.
For
example,
phenyl
mercaptan
(
i.
e.
benzenethiol)
is
a
fairly
toxic
chemical
producing
neurotoxicity,
liver
toxicity,
and
other
effects
and
has
a
rat
acute
oral
LD50
of
46
mg/
kg
(
McCord
&
Witheridge,
1949,
cited
in
NIOSH
website).
In
contrast,
the
oxidized
form,
benzenesulfonic
acid
is
reported
as
having
a
rat
acute
oral
LD50
of
890
mg/
kg
(
Benzenesulfonic
acid
MSDS).
This
marked
decrease
of
toxicity
can
be
attributed
to
polarity
resulting
from
the
replacement
of
the
­
SH
group
with
a
sulfonic
acid
group.

4.
2­
BTSA
is
the
oxidized
(
sulfonic
acid)
form
of
2­
MBT,
thus
it
is
expected
to
be
equally
or
less
systemically
toxic
than
2­
MBT
by
analogy
with
the
benzenethiol/
benzenesulfonic
acid
pair
of
compounds.
Barring
high
dose­
effects
such
as
gastrointestinal
effects,
the
chronic
RfD
for
2­
MBT
of
0.6
mg/
kg/
day
set
by
the
HED
RfD/
Peer
Review
Committee
suggests
that
the
chronic
toxicity
of
2­
BTSA
is
much
smaller
than
that
of
the
parent
TCMTB
with
a
chronic
RfD
of
0.013
mg/
kg/
day.
Although
there
are
concerns
for
the
carcinogenic
potential
of
2­
MBT
(
Group
C),
there
are
no
such
concerns
for
2­
BTSA
due
to
its
very
high
polarity
and
probably
absence
of
metabolism.

Additionally,
2­
MBT
and
other
TCMTB
metabolites
were
not
found
at
significant
levels
to
be
considered
residues
of
concern.
Therefore,
only
TCMTB
should
be
considered
a
residue
of
concern
in
plant
commodities.

For
drinking
water,
the
residues
of
concern
should
include
TCMTB
and
2­
MBT
and
is
based
on
the
available
aerobic
soil
metabolism
study
(
MRID
43532201).
2­
BTSA
was
found
at
71%
TRR,
however,
it
should
be
excluded
as
a
residue
of
concern
for
reasons
Page
21
of
66
noted
in
the
above
section.
2­
MBT
was
found
at
30%
TRR
after
1.5
days
post­
treatment
and
should
be
considered
a
residue
of
concern.
2­
MBT
is
distinctly
less
toxic
than
the
parent;
but
was
conservatively
included
in
the
drinking
water
assessment
because
it
is
considered
a
toxic
metabolite
of
concern.
All
other
metabolites
were
not
found
at
significant
levels;
therefore,
should
not
to
be
considered
residues
of
concern.

4.0
HAZARD
CHARACTERIZATION
4.1
Hazard
Profile
for
TCMTB
The
toxicology
database
for
TCMTB
is
considered
complete
for
a
food
use
pesticide.
No
additional
studies
are
required
at
this
time.
A
detailed
hazard
assessment
for
TCMTB
is
presented
in
the
attached
memorandum
(
memo
from
D.
Smegal,
April
4,
2006).

Acute
Toxicity.
TCMTB
exhibits
low
acute
oral
and
dermal
toxicity
(
toxicity
category
III).
However,
it
is
highly
irritating
to
the
eyes
and
skin
(
toxicity
category
I
and
II,
respectively)
and
is
also
considered
to
be
highly
toxic
via
the
inhalation
route
of
exposure
(
toxicity
category
I).
TCMTB
is
a
dermal
sensitizer.

Subchronic
Toxicity.
Following
subchronic
oral
exposures
to
rodents,
TCMTB
caused
increased
incidence
of
mild
to
severe
stomach
lesions
characterized
by
inflammation,
hyperplasia,
necrosis,
and
ulceration.
Inflammatory
cells
infiltration
and
edema
were
also
noted
at
a
low
incidence.
TCMTB
resulted
in
decreased
body
weight
gains
(
78
to
84%
of
control),
food
consumption
(
87­
95%
of
control)
and
food
efficiency.
In
a
21­
day
rat
dermal
toxicity
study,
TCMTB
produced
dose­
dependant
dermal
irritation
in
all
dose
groups
beginning
on
treatment
days
3­
4,
which
progressed
to
eschar
formation.
Rats
in
the
mid
and
high
dose
group
had
ulcers,
hemorrhages
and
chronic
dermatitis.
Decreased
body
weight
gain,
food
consumption,
and
hematological
(
changes
in
hemoglobin,
hematocrit,
and
segmented
neutrophils)
and
clinical
chemistry
changes
(
blood
urea
nitrogen,
glucose,
globulins,
and
elevated
serum
aspartate
aminotransferase
(
AST)
were
also
noted.
However,
the
clinical
chemistry
changes
did
not
correspond
to
any
treatment­
related
findings
in
the
liver
or
kidney.

Developmental
Toxicity.
Developmental
toxicity
studies
were
available
in
both
the
rat
and
rabbit
for
TCMTB.
Rabbits
appear
to
be
more
sensitive
to
the
toxicity
of
TCMTB
than
rats
based
on
maternal
toxicity.
In
rabbits,
the
maternal
NOAEL
and
LOAEL
were
16
and
32
mg
ai/
kg/
day,
respectively.
In
rats,
the
maternal
NOAEL
and
LOAEL
were
21
and
64
mg
ai/
kg/
day.
No
developmental
effects
were
noted
in
the
rabbit
at
the
highest
dose
tested
(
32
mg
ai/
kg/
day).
However,
in
the
rat
adverse
developmental
effects
including
increased
fetal
and
litter
incidence
of
fused/
wavy
ribs,
rudimentary
cervical,
thoracic
and
lumbar
ribs
and
increased
incidence
of
sternebrae
and
pelvic
girdle
anomalies
were
noted
at
doses
of
105
mg
ai/
kg/
day,
which
was
maternally
toxic.

Reproductive
Toxicity.
In
a
two­
generation
rat
reproduction
study,
there
were
no
treatment
related
effects
noted
at
the
highest
dose
tested
for
parental
toxicity
or
on
Page
22
of
66
reproductive
parameters
examined
in
this
study.
Slight,
statistically
significant
effects
were
noted
in
mean
body
weight
in
the
high
dose
offspring
in
the
second
mating
(
F2B)
around
lactation
day
21.
This
must
be
considered
as
systemic
toxicity
as
the
litters
began
with
relatively
similar
mean
body
weights,
and
around
lactation
day
14
the
pups
began
to
consume
diet
while
continuing
to
nurse.
Mean
pup
weight
was
not
significantly
reduced
at
days
7
or
14
in
the
F2B
pups,
and
there
were
no
consistent
effects
on
pup
weight
in
the
F0
and
F1a
generation
pups.
Thus,
the
Agency
believes
this
finding
in
the
F2B
pups
on
day
21
is
of
questionable
toxicological
significance.

Chronic
Toxicity.
Dogs
appear
to
be
the
most
sensitive
species
to
TCMTB
toxicity
following
chronic
exposure.
In
the
chronic
dog
toxicity
study,
adverse
effects
were
noted
at
the
lowest
dose
tested
of
3.8
mg/
kg/
day.
Adverse
effects
included
decreased
body
weight
gain,
hematological
effects
(
changes
in
white
blood
cells,
monocytes),
alterations
in
clinical
chemistry
parameters
(
plasma
ALT)
and
decreased
uterine
weight
in
females.

Carcinogenicity.
In
the
chronic
rat
toxicity/
carcinogenicity
study,
no
adverse
systemic
toxicity
effects
were
noted
at
the
highest
dose
tested
of
20
mg/
kg/
day.
However,
there
was
a
statistically
significant
increase
in
the
incidence
of
testicular
interstitial
cell
adenomas
in
males
of
mid
(
P=
0.0155)
and
high­
dose
(
P=
0.0087)
levels,
that
had
a
highly
significant
positive
dose­
related
trend
(
P=
0.0018).
Treatment
was
also
associated
with
a
possible
increased
incidence
of
thyroid
C­
cell
adenomas
in
females
of
the
mid­
and
high­
dose
levels,
which
had
a
highly
significant
(
P=
0.0067)
positive
dose­
related
trend,
but
did
not
attain
a
statistically
significant
level
in
the
pairwise
comparison
with
concurrent
controls.
No
historical
data
were
available
for
review.

In
the
chronic
mouse
toxicity/
carcinogenicity
study,
decreased
body
weight
gain
was
noted
in
both
sexes,
while
there
was
a
statistically
increased
incidence
of
focal
and
diffuse
hyperplasia
of
duodenal
mucosa
in
males
(
10/
42
vs
1/
41
in
controls)
at
150
mg
TCMTB/
kg/
day
(
122
mg
ai/
kg/
day).
There
was
no
evidence
of
carcinogenicity.

TCMTB
has
been
classified
as
Group
C
­
possible
human
carcinogen
­
and
the
Agency
recommended
that
for
the
purpose
of
risk
characterization,
the
Reference
Dose
(
RfD)
approach
be
used
for
quantitation
of
cancer
risk.
This
was
based
on
statistically
significant
increases
in
tumors
in
both
sexes
of
the
Sprague­
Dawley
rat:
testicular
interstitial
cell
adenomas
in
males
and
thyroid
c­
cell
adenomas
in
females.
The
RfD
approach
was
recommended
because
there
was
no
apparent
compound­
related
increase
in
tumors
in
the
mouse
carcinogenicity
study,
and
there
is
no
apparent
concern
for
mutagenicity
or
additional
support
from
Structure
Activity
Relationships
(
SAR).

Neurotoxicity.
The
available
toxicity
data
do
no
indicate
neurotoxicity
in
the
experimental
animals
exposed
to
TCMTB
by
either
oral
or
dermal
routes.

Genotoxicity.
TCMTB
was
negative
for
mutagenicity
in
the
gene
mutation
assay
with
bacteria,
and
did
not
cause
an
increase
in
unscheduled
DNA
synthesis
(
UDS)
in
rat
primary
hepatocytes
assay.
It
was
also
negative
for
chromosomal
aberrations
in
the
in
vivo
micronucleus
assay
in
mice.
Page
23
of
66
Tables
6
and
7
highlight
key
toxicological
studies
for
TCMTB.

Table
6.
Acute
Toxicity
Data
on
TCMTB
Technical
(
80%
ai)

Guideline
No./
Study
Type
MRID
No.
Results
Toxicity
Category
870.1100
Acute
oral
toxicity
41583801
LD50
=
750
mg/
kg
(
M+
F);
80%
ai
III
870.1200
Acute
dermal
toxicity
41515401
LD50
>
2000
mg/
kg
(
M+
F);
80%
ai
III
870.1300
Acute
inhalation
toxicity
41640601
LC50=
0.07
mg/
L;
80%
ai
I
870.2400
Acute
eye
irritation
Acc
No.
111991
Diluted
Busan
72
(
60
%
ai):
primary
irritation
score
(
PIS)=
2/
110
(
slight
conjunctival
redness,
no
corneal
opacity);
undiluted
Busan
72
(
60%
ai)
PIS=
34/
110
(
blanched
conjunctivae,
chemosis,
corneal
opacity
not
reversible
by
day
7)
I
870.2500
Acute
dermal
irritation
41583701
primary
irritation
index=
7.42
with
severe
erythema
and
edema
observed
at
72
hours;
80%
ai
II
870.2600
Skin
sensitization
MRID
42349201
Acc
No.
259676
Busan
74
(
80%
ai)
caused
delayed
contact
hypersensitivity
in
guinea
pigs
when
induced
and
challenged
by
a
40%
w/
v
aqueous
concentration
of
active
ingredient.
Sensitizer.
­­

Table
7.
Toxicity
Profile
of
TCMTB
Guideline
No./
Study
Type
MRID
No.
(
year)/
Classification
/
Doses
(
a)
Results
870.3100
13­
week
oral
toxicity
rodents
(
Range
finding)
(
Diet)

Batch
1517
43112801
(
1987)
unacceptable/
guideline
(
range
finding
study)
0,
10,
30,
70
and
100
mgTCMTB/
kg/
day
in
diet
(
0,
8.2,
24.5,
57
and
81.6
mg
ai/
kg/
day)

M:
0,
10.2,
31,70
and
100
mg/
kg/
day
F:
0,
10.3,
31,
72,
99
mg
/
kg/
day
81.56%
ai
purity
NOAEL
=
10.2
mg/
kg/
day(
M);
10.3
mg/
kg/
day
(
F)
(
8.3
mg
ai/
kg/
day)
LOAEL
=
31
mg/
kg/
day
(
M+
F)
(
25
mg
ai/
kg/
day)
based
on
increased
incidence
of
squamous
epithelial
hyperplasia
of
the
stomach
and
decreased
in
body
weight
gains,
food
consumption
and
food
efficiency
in
both
sexes
of
the
70
and
100
mg/
kg/
day
dose
groups.
Page
24
of
66
Table
7.
Toxicity
Profile
of
TCMTB
Guideline
No./
Study
Type
MRID
No.
(
year)/
Classification
/
Doses
(
a)
Results
870.3100
90­
Day
oral
toxicity
rodents
(
diet)

Lot
9­
3573
92179026
(
1980)
unacceptable/
guideline
0,
333,
500,
750
ppm
in
diet
0,
16.7,
25,
37.5
mgTCMTB/
kg/
day
which
is
equivalent
to
13.4,
20
and
30
mg
ai/
kg/
day
Purity
approximately
80%
ai.
(
as
supplied
by
the
registrant)
NOAEL
=
25
mg
TCMTB/
kg/
day
(
20
mg
ai/
kg/
day)
LOAEL
=
37.5
mg
TCMTB/
kg/
day(
30
mg
ai/
kg/
day)
based
on
increased
incidence
of
histopathology
of
the
stomach,
including
inflammation,
necrosis
and
ulceration.

870.3700a
Prenatal
developmental
in
rodents
Lot
511230
00154295,
92179009
(
1985)
0,
25.1,
76.5,
125.5
mg/
kg
via
gavage
acceptable
guideline
83.6%
ai
purity
Equivalent
to
21,
64
and
105
mg
ai/
kg/
day
Maternal
NOAEL
=
21
mg
ai/
kg/
day
(
25.1
mg
TCMTB/
kg/
day)
LOAEL
=
64
mg
ai/
kg/
day
(
76.5
mg
TCMTB/
kg/
day)
based
on
clinical
signs
of
ventral
alopecia,
rough
coat,
dyspnea/
wheezing,
oral
discharge,
diarrhea/
loose
stool,
urine
staining,
piloerection
and
hunched
gait
along
with
reduced
body
weight
gain.

Developmental
NOAEL
=
64
mg
ai/
kg/
day
(
76.5
mg
TCMTB/
kg/
day)
LOAEL
=
105
mg
ai/
kg/
day
(
125.5
mg
TCMTB/
kg/
day)
based
on
skeletal
anomaly
observations
consisting
of
fused/
wavy
ribs,
rudimentary
cervical
thoracic
and
lumbar
ribs,
increased
number
of
sternebrae
and
pelvic
girdle
anomalies.

870.3700b
Prenatal
developmental
in
nonrodents
Lot
5­
13002
40075101,
40075102,
92179011
(
1986)
acceptable
guideline
0,
10,
20,
40
mgTCMTB/
kg/
day
via
gavage
of
81%
ai
purity
Equivalent
to
0,
8,
16
and
32
mg
ai/
kg/
day
Maternal
NOAEL
=
16
mg
ai/
kg/
day
(
20
mg
TCMTB/
kg/
day
)
LOAEL
 
=
32
mg
ai/
kg/
day
(
40
mg
TCMTB/
kg/
day)
based
on
decreased
body
weight
gain
and
food
consumption.

Developmental
NOAEL 
 
32
mg
ai/
kg/
day
(
40
mg
TCMTB
/
kg/
day)
LOAEL=.
32
mg
ai/
kg/
day
(
40
mg
TCMTB
/
kg/
day).

Two
generation
reproduction
study
in
rats
Batch
1517
41471401,
92179011
(
1988)
acceptable
guideline
0,
25,
100
and
400
ppm;
M:
0,
2.4,
9.6,
38.4
mg/
kg/
day;

F:
0,
3,
11.7,
45.5
mg/
kg/
day
81.6%
ai
purity
Offspring
NOAEL
(
HDT)
=
38.4
mg/
kg/
day
(
M);
45.5
mg/
kg/
day
(
F)
mg/
kg/
day
(
400
ppm)
Offspring
LOAEL
=
Not
identified
Parental/
systemic
NOAEL
=
38.4
mg/
kg/
day
(
M);
45.5
mg/
kg/
day
(
F)
(
HDT)
(
400
ppm)
Parental/
systemic
LOAEL
=
Not
identified.

Reproductive
NOAEL
=
38.4
mg/
kg/
day
(
M);
45.5
mg/
kg/
day
(
F)
(
HDT)
(
400
ppm)
LOAEL
=
Not
identified.

83­
1a
Chronic
toxicity
in
rats
Batch
1517
41529701,
41570301,
42116301
(
1989)
acceptable
guideline
0,
2,
8
and
20
mg/
kg/
day
81.6%
ai
purity
NOAEL=
20
mg/
kg/
day
LOAEL=
not
identified.
Statistically
significant
increase
in
the
incidence
of
testicular
interstitial
cell
adenomas
in
males
of
mid
(
P=
0.0155)
and
high­
dose
(
P=
0.0087)
levels,
that
had
a
highly
significant
positive
dose­
related
trend
(
P=
0.0018).
Treatment
was
also
associated
with
a
possible
increased
incidence
of
thyroid
C­
cell
adenomas
in
females
of
the
mid­
and
high­
dose
levels,
which
had
a
highly
significant
(
P=
0.0067)
positive
dose­
related
trend,
but
did
not
attain
a
statistically
significant
level
in
the
pairwise
comparison
with
concurrent
controls.
No
historical
data
were
available
for
review.

83­
2
Chronic
toxicity/
Carcinogenicity
in
mice
Batch
1517
42383001
(
1990)
acceptable
guideline
0,
5,
50,
150
mg/
kg/
day
which
is
equivalent
to
4,
41
and
122
mg
ai/
kg./
day
based
on
81.6%
ai
purity
NOAEL=
50
mg
TCMTB/
kg/
day
(
41
mg
ai/
kg/
day)
LOAEL=
150
mg
TCMTB/
kg/
day
(
122
mg
ai/
kg/
day)
based
on
decreased
body
weight
gain
in
both
sexes,
statistically
increased
incidence
of
focal
and
diffuse
hyperplasia
of
duodenal
mucosa
in
males
(
10/
42
vs
1/
41
in
controls).
No
evidence
of
carcinogenicity.
Page
25
of
66
Table
7.
Toxicity
Profile
of
TCMTB
Guideline
No./
Study
Type
MRID
No.
(
year)/
Classification
/
Doses
(
a)
Results
One­
year
dog
Batch
1517
41342201,
92179008
(
1989)
unacceptable
guideline
(
No
NOAEL)
0,
100,
300
and
1000
ppm;
M:
0,
3.8,
11.7
and
38.8
mg/
kg/
day
F:
0,
4,
11.2,
43.2
mg/
kg/
day
81.6%
ai
purity
NOAEL=
not
identified
(<
100
ppm
or
3.8
mg/
kg/
day)
LOAEL=
3.8
mg/
kg/
day
(
M)
and
4
mg/
kg/
day
(
F)
based
on
decreased
body
weight
gain,
white
cells,
monocytes
and
plasma
ALT
in
males
and
decreased
plasma
ALT
and
uterine
weight
in
females.

21­
Day
dermal
toxicity
study
­­
Rat
Lot
OB­
8483
41655801
(
1990)

0,
25,
100
and
250
mg/
kg/
day
which
is
equivalent
to
0,
20.6,
82.3
and
206
mg
ai/
kg/
day
based
on
82..
33%
ai
purity
Systemic
NOAEL=
20.6
mg
ai/
kg/
day
(
25
mgTCMTB/
kg/
day)
Systemic
LOAEL=
82.3
mg
ai/
kg/
day
(
100
mg
TCMTB/
kg/
day)
based
on
decreased
body
weight
gain
and
food
consumption
in
males,
in
addition
to
significant
hematalogical
(
increased
neutrophils,
decreased
hemoglobin,
hematocrit
and
erythrocytes)
and
clinical
chemistry
changes
(
increased
urea
nitrogen,
glucose
and
globulins)

Dermal
NOAEL=
not
identified
Dermal
LOAEL=
20.6
mg
ai/
kg/
day
(
25
mg
T
CMTB/
kg/
day)
for
dermal
effects
based
on
dose­
dependent
irritation
which
progressed
to
eschar
formation
in
2
rats
of
the
low
dose
group,
and
in
all
rats
of
mid­
and
high­
dose
group.
Mid
and
high
dose
group
exhibited
ulcers,
hemorrhages
and
chronic
dermatitis.

870.5100/
84­
2
Mutagenicity
study:
Gene
mutation
(
S.
Typhimurium)
MRID
41386101
acceptable
TCMTB
was
negative
for
inducing
reverse
gene
mutations
in
Salmonella
typhimurium
strains
TA1535,
TA1537,
TA1538,
TA
98
or
TA
100
exposed
in
the
presence
of
absence
of
S9
activation
up
to
cytotoxic
concentrations
(
 
33.3
ug/
plate
­
S9;

 
66.7
ug/
plate
+
S9).
The
results
were
confirmed
in
an
independently
performed
trial.

870.5395/
84­
2
Structural
Chromosomal
Aberrations:
Clastogenic
Evaluation
in
in
vivo
mouse
micronucleus
assay
MRID
00165520
Acceptable;
EPA
Accession
No.
266152
TRID
470330­
022
Purity
not
provided
In
a
structural
chromosomal
aberration
assay,
the
high
dose
of
TCMTB
(
500
mg/
kg)
exhibited
mortality
and
signs
of
clinical
toxicity.
No
evidence
of
an
increase
in
micronucleated
polychromatic
erythrocytes
(
PCE)
was
noted
at
the
dose
levels
tested
in
this
study
(
50,
167,
and
500
mg/
kg).
There
was
evidence
of
some
PCE
depression
at
the
high
dose
in
the
48
and
72
hour
animals.

870.5550/
84­
4
Rat
Primary
Hepatocyte
Unscheduled
DNA
Synthesis
Assay
MRID
00165518
Acceptable;

TRID
470330­
020
EPA
Accession
No.
266150
Purity
not
provided;
Lot
No.
5­
13002
TCMTB
did
not
cause
a
significant
increase
in
the
unscheduled
DNA
synthesis
(
UDS)
in
rat
primary
hepatocytes
as
measured
in
this
study.
Concentrations
used
were
0.05­
25
ug/
ml
in
DMSO.

(
a)
Doses
are
presented
as
both
TCMTB
tested,
and
as
active
ingredient,
where
available:
TCMTB
(
mg
TCMTB/
kg/
day)*
purity
tested
in
study=
mg
active
ingredient
(
ai)/
kg/
day.
Example
calculation
from
rabbit
developmental
toxicity
study:
40
mg
TCMTB/
kg/
day
*
0.81
(
purity)
=
32
mg
ai/
kg/
day.

4.2
Hazard
Profile
for
2­
Mercaptobenzothiazole
(
2­
MBT)

2­
Mercaptobenzothiazole
(
2­
MBT)
is
the
main
mammalian
metabolite
of
TCMTB
(
Manninen
et
al.,
Arch.
Toxicol.
70:
579­
584,
1996).
Although
the
current
uses
of
2­
MBT
Page
26
of
66
have
been
cancelled,
it
is
instructive
to
summarize
the
hazard
of
2­
MBT
relative
to
that
of
TCMTB,
as
this
will
be
the
main
metabolite
that
mammalian
organisms
could
potentially
be
exposed
to
in
the
diet
when
TCMTB
is
used.

2­
MBT
shows
low
acute
toxicity
by
the
oral
route
(
Toxicity
Category
IV,
MRID
41571901)
and
dermal
route
(
LC50
>
2000
mg/
kg,
Toxicity
Category
III,
MRID
41571902).
2­
MBT
was
minimally
irritating
to
the
eyes
(
Toxicity
Category
III,
MRID
41571903)
and
slightly
irritating
to
the
skin
(
Toxicity
Category
IV,
MRID
41571904).
A
dermal
sensitization
study
submitted
for
the
zinc
salt
of
2­
MBT
showed
no
evidence
of
hypersensitivity
when
tested
using
the
modified
Buehler
test
method
(
MRID
41571905).

A
90­
day
oral
toxicity
study
conduced
with
2­
MBT
(
96.3%
a.
i.)
by
the
National
Toxicology
Program
at
doses
of
187.5,
375,
750,
and
1500
mg/
kg/
day
(
technical
report
no.
332)
in
rats
showed
decreased
body
weight
gain
at
1500
mg/
kg/
day
in
both
sexes
compared
to
control,
and
increased
liver
weight
at
1500
mg/
kg/
day.
A
90­
day
toxicity
study
by
the
NTP
with
2­
MBT
in
mice
at
doses
of
0,
94,
188,
375,
750,
and
1500
mg/
kg/
day
showed
mortality
at
the
high
dose
(
5/
10
males
and
7/
10
females),
clonic
seizures,
lacrimation,
and
salivation
at
750
and
1500
mg/
kg/
day,
and
lethargy
and
rough
coat
at
375
and
750
mg/
kg/
day.
There
were
no
gross
or
microscopic
pathological
effects
noted
in
mice.

In
a
13­
week
dermal
toxicity
study
with
2­
MBT
(
98.22%),
administration
of
2­
MBT
at
doses
of
0,
200,
1000,
and
2000
mg/
kg/
day
resulted
in
increased
relative
liver
weight
at
1000
and
2000
mg/
kg/
day,
the
only
effect
noted
in
this
study
(
MRID
42146301).

In
a
developmental
toxicity
study
in
rats
(
MRID
41422202),
2­
MBT
(
98.5%
a.
i.)
was
administered
to
mated
female
SD
Crl:
COBS
CD
BR
VAF
rats
(
26/
dose)
at
doses
of
0,
300,
1200,
and
1800
mg/
kg/
day
on
gestation
days
6
through
15
inclusive.
At
1200
mg/
kg/
day,
maternal
toxicity
was
observed
in
the
form
of
salivation
and
urine
staining.
There
was
no
evidence
of
developmental
toxicity
related
to
administration
of
2­
MBT
in
this
study.
The
Maternal
NOAEL
=
300
mg/
kg/
day
and
the
Maternal
LOAEL
=
1200
mg/
kg/
day,
based
on
increased
salivation
and
urine
staining.
The
Developmental
NOAEL
>
1800
mg/
kg/
day
and
the
Developmental
LOAEL
>
1800
mg/
kg/
day.

In
a
2­
generation
reproduction
toxicity
study
(
MRID
41912501),
2­
MBT(
98.0­
98.5%
a.
i.)
was
administered
in
the
diet
to
groups
of
COBS
BR
rats
at
doses
of
0,
194,
695,
and
1195
mg/
kg/
day
[
males]
and
0,
218,
783,
and
1327
mg/
kg/
day
[
females]).
At
the
high
dose,
decreased
body
weight
and
weight
gain
were
observed
as
well
as
increased
incidence
of
microscopic
changes
in
the
kidney.
Fertility,
length
of
gestation,
and
pup
viability
were
unaffected
by
2­
MBT
treatment.
Pup
growth
(
in
the
form
of
decreased
body
weight)
was
decreased
at
the
695/
783
and
1195/
1327
mg/
kg/
day
dose
levels
by
9%
and
15%
respectively
on
day
14
and
by
13%
and
21%
on
day
21
in
the
first
generation,
and
was
decreased
significantly
(
9­
13%)
at
all
dose
levels
in
the
second
generation
on
days
14
and
21.
The
systemic/
reproductive
toxicity
NOAEL
=
194
mg/
kg/
day
and
the
systemic/
reproductive
toxicity
LOAEL
=
695
mg/
kg/
day
based
on
decreases
in
body
weight
in
parental
animals
and
in
offspring
at
this
dose.
Page
27
of
66
In
carcinogenicity
studies
conducted
by
the
NTP,
there
was
some
evidence
of
carcinogenicity
for
2­
MBT
in
male
and
female
rats.
The
evidence
included
increased
incidences
of
pituitary
adenomas/
adeno­
carcinomas
and
adrenal
gland
pheochromocytomas
in
both
female
dosed
groups
and
increased
incidences
of
adrenal
gland
pheochromocytomas/
malignant
pheochromocytomas
and
preputial
gland
adenomas/
carcinomas
in
both
male
dosed
groups
along
with
an
increased
incidence
of
mononuclear
cell
leukemia
and
pancreatic
acinar
cell
adenomas
in
the
low
dose
males.
For
both
male
dosed
groups,
however,
the
treatment
levels
appeared
to
be
excessive.

Based
on
the
available
data
from
the
NTP
report,
2­
MBT
appears
to
be
carcinogenic
in
female
mice
based
on
increased
incidences
of
hepatocellular
adenomas
or
carcinomas
(
combined)
in
the
low
dose
females.
The
high
dose
tested
in
this
study
was
excessive
based
on
the
increased
mortality
noted
in
high
dose
females.

2­
MBT
was
negative
in
a
salmonella
(
Ames)
assay,
a
rat
dominant
lethal
test,
a
CHO/
HGPRT
test
[
gene
mutation],
and
a
mouse
micronucleus
test
[
chromosomal
aberration].
2­
MBT
was
positive
both
with
and
without
metabolic
activation
in
a
mouse
lymphoma
test
[
gene
mutation].
MBT­
sodium
salt
was
negative
in
a
rat
hepatocyte
unscheduled
DNA
synthesis
assay.

The
HED
RfD/
Peer
Review
committee
met
in
April
of
1994
to
establish
a
Reference
Dose
for
2­
MBT.
The
committee
recommended
that
the
RfD
be
established
on
the
basis
of
the
2­
generation
reproduction
toxicity
study
using
the
NOAEL
value
of
194
mg/
kg/
day.
Using
a
total
uncertainty
factor
of
300
(
10x
interspecies
extrapolation,
10x
intraspecies
variation,
3x
for
lack
of
a
chronic
toxicity
study
in
non­
rodents
[
per
the
RfD
peer
review
committee
memo]),
the
RfD
committee
calculated
a
Reference
Dose
for
2­
MBT
of
0.6
mg/
kg/
day.
Note
that
this
chronic
RfD
value
is
considerably
higher
than
that
for
the
parent
TCMTB
(
0.01
mg/
kg/
day),
consistent
with
the
toxicity
database
which
shows
lower
toxicity
for
2­
MBT
than
TCMTB.

The
HED
Carcinogenicity
Peer
Review
Committee
decided
that
2­
MBT
should
be
classified
as
Group­
C
possible
human
carcinogen
and
recommended
that
for
the
purpose
of
risk
characterization
the
Reference
Dose
(
RfD)
approach
should
be
used
for
quantification
of
human
risk.
This
decision
to
use
the
RfD
approach
was
based
on
some
evidence
of
adrenal
gland
tumors
in
male
and
female
rats
and
some
evidence
of
preputial
gland
tumors
in
male
rats.
There
is
equivocal
evidence
for
pituitary
gland
tumors
in
male
rats.
The
evidence
for
hepatocellular
tumors
in
mice
was
also
equivocal.
2­
MBT
was
also
considered
to
have
genotoxic
activity.
The
q1*
approach
to
risk
assessment
was
not
used
since
the
tumors
were
found
in
only
1
species
and
there
was
no
clear
evidence
of
carcinogenicity
from
any
of
the
tumor
types.

4.3
FQPA
Considerations
Under
the
Food
Quality
Protection
Act
(
FQPA),
P.
L.
104­
170,
which
was
Page
28
of
66
promulgated
in
1996
as
an
amendment
to
the
Federal
Insecticide,
Fungicide,
and
Rodenticide
Act
(
FIFRA)
and
the
Federal
Food,
Drug
and
Cosmetic
Act
(
FFDCA),
the
Agency
was
directed
to
"
ensure
that
there
is
a
reasonable
certainty
that
no
harm
will
result
to
infants
and
children"
from
aggregate
exposure
to
a
pesticide
chemical
residue.
The
law
further
states
that
in
the
case
of
threshold
effects,
for
purposes
of
providing
this
reasonable
certainty
of
no
harm,
"
an
additional
tenfold
margin
of
safety
for
the
pesticide
chemical
residue
and
other
sources
of
exposure
shall
be
applied
for
infants
and
children
to
take
into
account
potential
pre­
and
post­
natal
toxicity
and
completeness
of
the
data
with
respect
to
exposure
and
toxicity
to
infants
and
children.
Notwithstanding
such
requirement
for
an
additional
margin
of
safety,
the
Administrator
may
use
a
different
margin
of
safety
for
the
pesticide
residue
only
if,
on
the
basis
of
reliable
data,
such
margin
will
be
safe
for
infants
and
children."

The
toxicology
data
base
is
complete
with
respect
to
assessing
the
increased
susceptibility
to
infants
and
children
as
required
by
FQPA
for
TCMTB.
The
rat
and
rabbit
prenatal
developmental
studies
and
2­
generation
reproduction
study
showed
no
quantitative
evidence
of
increased
susceptibility
(
i.
e.,
developmental/
offspring
NOAELs/
LOAELs
were
the
same
as
or
higher
than
those
for
maternal
effects).
In
addition,
there
were
no
effects
on
reproductive
parameters
in
the
2­
generation
reproductive
study.
Based
on
hazard
data,
the
ADTC
recommended
the
special
FQPA
SF
be
reduced
to
1X
because
there
are
no
concerns
and
no
residual
uncertainties
with
regard
to
pre­
and/
or
postnatal
toxicity.

4.4
Dose­
Response
Assessment
The
doses
and
toxicological
endpoints
selected
by
the
Antimicrobials
Division
Toxicity
Endpoint
Selection
Committee
(
ADTC)
for
various
exposure
scenarios
are
summarized
below.

Table
8.
Summary
of
Toxicological
Dose
and
Endpoints
for
TCMTB
Exposure
Scenario
Dose
Used
in
Risk
Assessment
(
mg/
kg/
day)
Target
MOEs/
UFs
FQPA
safety
factor
for
Risk
Assessment
Study
and
Toxicological
Effects
Acute
Dietary
(
all
populations,
including
infants
and
children)
NOAEL=
25.1
mg/
kg/
day
83.55%
ai
purity
UF
=
100
(
10x
inter­
and
intra­
species
extrapolation)

FQPA
SF
=
1x
Acute
PAD
=
0.25
mg
TCMTB/
kg/
day
Developmental
toxicity
study
in
rats
(
MRID
00154295,
92179009
(
1985))

Maternal
LOAEL
=
76.5
mg
TCMTB/
kg/
day,
based
on
clinical
signs
of
toxicity
(
ventral
alopecia,
rough
coat,
dyspnea/
wheezing,
oral
discharge,
diarrhea/
loose
stool,
urine
staining,
piloerection,
and
hunched
gait).

Acute
Dietary
(
females
13­
49)
An
endpoint
specific
for
females
13­
49
was
not
identified
because
the
Acute
Dietary
endpoint
for
all
populations
is
protective
of
developmental
effects.
Page
29
of
66
Table
8.
Summary
of
Toxicological
Dose
and
Endpoints
for
TCMTB
Exposure
Scenario
Dose
Used
in
Risk
Assessment
(
mg/
kg/
day)
Target
MOEs/
UFs
FQPA
safety
factor
for
Risk
Assessment
Study
and
Toxicological
Effects
Chronic
Dietary
(
all
populations)
LOAEL
=
3.8
mg/
kg/
day
81.6%
ai
purity
UF
=
300
(
10x
inter­
and
intra­
species
extrapolation,
3x
for
use
of
a
LOAEL)

FQPA
SF
=
1x
Chronic
PAD
=
0.01
mg
ai/
kg/
day
Chronic
toxicity
study
in
dogs
(
MRID
41342201,
92179008
(
1989))

LOAEL
=
3.8
mg/
kg/
day
(
males),
based
on
decreased
body
weight
gain,
decreased
white
cells,
monocytes,
and
plasma
ALT;
decreased
uterine
weight
in
females.

Short­
and
Intermediate­
Term
Incidental
Oral
(
1­
30
days;
30
days­
6
months)
NOAEL=
16.2
mg
ai/
kg/
day
81%
ai
purity
(
20
mg
TCMTB/
kg/
day)
MOE
=
100
(
10X
for
inter­
and
intraspecies
extrapolation)
Developmental
toxicity
study
in
rabbits
(
MRID
40075101,
40075102,
92179011
(
1986))

LOAEL
=
32
mg
ai/
kg/
day
(
40
mg
TCMTB/
kg/
day),
based
on
decreased
body
weight
gain
and
food
consumption
in
maternal
animals.

Dermal
(
all
durations)
(
1­
30
days;
30
days­
6
months;
>
6
months)
NOAEL=
25
mg/
kg/
day
82.33%
ai
purity
(
20.6
mg
ai//
kg/
day)
MOE
=
100
(
ST
and
IT)

MOE
=
300
(
LT)

(
10X
for
inter­
and
intraspecies
extrapolation,
and
3X
for
duration
of
exposure)
21­
Day
dermal
toxicity
study
in
rats
(
MRID
41655801)

LOAEL
=
100
mg
TCMTB/
kg/
day
(
82.3
mg
ai/
kg/
day),
based
on
decreased
body
weight
gain,
food
consumption,
and
hematological
and
clinical
chemistry
changes
Inhalation
(
short­
and
intermediate­
term)
NOAEL=
16.2
mg
ai/
kg/
day
81%
ai
purity
(
20
mg
TCMTB/
kg/
day)

Absorption=
100%
(
inhalation
and
oral
equivalent)
MOE
=
100
(
ST
and
IT)
(
a)
(
10X
for
inter­
and
intraspecies
extrapolation)
Developmental
toxicity
study
in
rabbits
(
MRID
40075102)

LOAEL
=
=
32
mg
ai/
kg/
day
(
40
mg
TCMTB/
kg/
day),
based
on
decreased
body
weight
gain
and
food
consumption
in
maternal
animals
Inhalation
(
long­
term)
LOAEL
=
3.8
mg/
kg/
day
81.6%
ai
purity
Absorption=
100%
(
inhalation
and
oral
MOE
=
300
(
a)

(
10X
for
inter­
and
intraspecies
extrapolation
and
3X
for
use
of
a
Chronic
toxicity
study
in
dogs
(
MRID
41342201,
92179008
(
1989))

LOAEL
=
3.8
mg/
kg/
day
(
males),
based
on
decreased
body
weight
gain,
decreased
Page
30
of
66
Table
8.
Summary
of
Toxicological
Dose
and
Endpoints
for
TCMTB
Exposure
Scenario
Dose
Used
in
Risk
Assessment
(
mg/
kg/
day)
Target
MOEs/
UFs
FQPA
safety
factor
for
Risk
Assessment
Study
and
Toxicological
Effects
equivalent)
LOAEL)
white
cells,
monocytes,
and
plasma
ALT;
decreased
uterine
weight
in
females.

Carcinogenicity
The
CPRC
concluded
that
TCMTB
should
be
classified
as
Group
C
­
possible
human
carcinogen
­
and
recommended
that
for
the
purpose
of
risk
characterization,
the
Reference
Dose
(
RfD)
approach
should
be
used
for
quantitation
of
human
risk.
This
was
based
on
statistically
significant
increases
in
tumors
in
both
sexes
of
the
Sprague­
Dawley
rat:
testicular
interstitial
cell
adenomas
in
males
and
thyroid
C­
cell
adenomas
in
females.
UF
=
uncertainty
factor,
FQPA
SF
=
Special
FQPA
safety
factor,
NOAEL
=
no
observed
adverse
effect
level,
LOAEL
=
lowest
observed
adverse
effect
level,
PAD
=
population
adjusted
dose
(
a
=
acute,
c
=
chronic)
RfD
=
reference
dose,
MOE
=
margin
of
exposure,
LOC
=
level
of
concern,
NA
=
Not
Applicable
(
a)
Note:
an
additional
UF
of
10X
is
used
for
route
extrapolation
from
an
oral
endpoint
to
determine
if
a
confirmatory
inhalation
study
is
warranted.
If
results
are
below
a
MOE
of
1,000,
a
confirmatory
inhalation
study
may
be
required.

4.5
Endocrine
Disruption
EPA
is
required
under
the
FFDCA,
as
amended
by
FQPA,
to
develop
a
screening
program
to
determine
whether
certain
substances
(
including
all
pesticide
active
and
other
ingredients)
"
may
have
an
effect
in
humans
that
is
similar
to
an
effect
produced
by
a
naturally
occurring
estrogen,
or
other
such
endocrine
effects
as
the
Administrator
may
designate."
Following
recommendations
of
its
Endocrine
Disruptor
and
Testing
Advisory
Committee
(
EDSTAC),
EPA
determined
that
there
was
a
scientific
basis
for
including,
as
part
of
the
program,
the
androgen
and
thyroid
hormone
systems,
in
addition
to
the
estrogen
hormone
system.
EPA
also
adopted
EDSTAC's
recommendation
that
the
Program
include
evaluations
of
potential
effects
in
wildlife.
For
pesticide
chemicals,
EPA
will
use
FIFRA
and,
to
the
extent
that
effects
in
wildlife
may
help
determine
whether
a
substance
may
have
an
effect
in
humans,
FFDCA
authority
to
require
the
wildlife
evaluations.
As
the
science
develops
and
resources
allow,
screening
of
additional
hormone
systems
may
be
added
to
the
Endocrine
Disruptor
Screening
Program
(
EDSP).

In
rats,
TCMTB
was
associated
with
testicular
and
thyroid
C­
cell
adenomas
that
could
possibly
be
related
to
endocrine
disruption.
When
additional
appropriate
screening
and/
or
testing
protocols
being
considered
under
the
Agency's
EDSP
have
been
developed,
TCMTB
may
be
subjected
to
further
screening
and/
or
testing
to
better
characterize
effects
related
to
endocrine
disruption.

5.0
PUBLIC
HEALTH
DATA
A
detailed
summary
of
the
human
incident
data
is
presented
in
the
memorandum
from
J.
Chen
April
18,
2006.
Below
is
a
brief
summary
of
this
information.
The
Agency
Page
31
of
66
conducted
a
literature
search
and
also
consulted
the
following
databases
for
poisoning
incident
data
for
TCMTB:

(
1)
OPP
Incident
Data
System
(
IDS)
­
The
Incident
Data
System
of
The
Office
of
Pesticide
Programs
(
OPP)
of
the
Environmental
Protection
Agency
(
EPA)
contains
reports
of
incidents
from
various
sources,
including
registrants,
other
federal
and
state
health
and
environmental
agencies
and
individual
consumers,
submitted
to
OPP
since
1992.
Reports
submitted
to
the
Incident
Data
System
represent
anecdotal
reports
or
allegations
only,
unless
otherwise
stated.
Typically
no
conclusions
can
be
drawn
implicating
the
pesticide
as
a
cause
of
any
of
the
reported
health
effects.
Nevertheless,
sometimes
with
enough
cases
and/
or
enough
documentation
risk
mitigation
measures
may
be
suggested.
(
2)
Poison
Control
Centers
(
1993­
2003)
­
as
the
result
of
a
data
purchase
by
EPA,
OPP
received
Poison
Control
Center
data
covering
the
years
1993
through
2003
for
all
pesticides.
Most
of
the
national
Poison
Control
Centers
(
PCCs)
participate
in
a
national
data
collection
system,
the
Toxic
Exposure
Surveillance
System,
which
obtains
data
from
about
65­
70
centers
at
hospitals
and
universities.
PCCs
provide
telephone
consultation
for
individuals
and
health
care
providers
on
suspected
poisonings,
involving
drugs,
household
products,
pesticides,
etc.
(
3)
California
Department
of
Pesticide
Regulation
(
1982­
2004)
­
California
has
collected
uniform
data
on
suspected
pesticide
poisonings
since
1982.
Physicians
are
required,
by
statute,
to
report
to
their
local
health
officer
all
occurrences
of
illness
suspected
of
being
related
to
exposure
to
pesticides.
The
majority
of
the
incidents
involve
workers.
Information
on
exposure
(
worker
activity),
type
of
illness
(
systemic,
eye,
skin,
eye/
skin
and
respiratory),
likelihood
of
a
causal
relationship,
and
number
of
days
off
work
and
in
the
hospital
are
provided.
(
4)
National
Pesticide
Telecommunications
Network
(
NPTN)
­
NPTN
is
a
toll­
free
information
service
supported
by
OPP.
A
ranking
of
the
top
200
active
ingredients
for
which
telephone
calls
were
received
during
calendar
years
1984­
1991,
inclusive,
has
been
prepared.
The
total
number
of
calls
was
tabulated
for
the
categories
human
incidents,
animal
incidents,
calls
for
information,
and
others.

There
are
incidents
associated
with
exposure
to
end­
use
products
containing
TCMTB.
Dermal
and
inhalation
are
the
primary
routes
of
exposure.
Most
of
the
incidents
are
related
to
an
irritation
type
reaction.
The
most
common
symptoms
reported
for
cases
of
dermal
exposure
were
skin
irritation/
burning,
rash,
itching,
skin
discoloration/
redness
and
blistering.
The
most
common
symptoms
reported
for
cases
of
ocular
exposure
were
eye
irritation/
burning.
Eye
pain
and
swelling
of
eyes
has
also
been
reported
in
some
incidents.

The
most
common
symptoms
reported
for
cases
of
inhalation
exposure
were
respiratory
irritation/
burning,
irritation
to
mouth/
throat/
nose,
coughing/
choking,
shortness
of
breath,
and
sore
throat.
Page
32
of
66
Although
oral
exposure
is
considered
to
be
a
minor
route
of
exposure
for
TCMTB
use,
irritation
to
the
mouth/
throat/
nose,
abdominal
pain,
kidney
failure,
and
hypothermia
and
loss
of
consciousness
were
reported
in
the
cases
of
ingestion.

6.0
EXPOSURE
ASSESSMENT
AND
CHARACTERIZATION
Dietary
exposure
to
TCMTB
can
occur
from
its
use
as
a
fungicide
for
seed
treatment,
and
also
from
its
use
as
a
slimicide
and
preservative
in
pulp
and
paper.
TCMTB
is
used
as
a
microbiocide/
microbiostat
and
bacteriocide/
bacteriostat
in
commercial/
institutional
premises,
residential
and
public
access
areas,
and
is
used
in
industrial
processes
and
water
systems,
and
as
wood
preservatives.
Exposure
to
residents
can
occur
from
TCMTB­
containing
paint
products.
Postapplication
residential
exposure
can
occur
in
adults
and
children
from
dermal
contact
with
treated
textiles/
leather
products,
as
well
as
in
children
from
treated
carpets.
Residential
exposures
to
TCMTB­
treated
wood
products
are
expected
to
be
minimal
because
the
wood
preservative
use
is
primarily
for
sapstain
control.
Occupational
exposure
to
TCMTB
can
occur
from
seed
treatment,
mixing/
loading/
application
activities
in
various
commercial/
institutional/
industrial
premises,
metal
working
fluids,
and
wood
preservation
treatment
for
sapstain
control.

6.1
Summary
of
Registered
Uses
TCMTB
is
a
fungicide
used
in
commercial
and
on­
farm
seed
treatment
settings.
It
is
a
slimicide
regulated
by
the
FDA
(
21
CFR
176.300)
for
controlling
bacteria,
fungi
and
yeasts
which
cause
deterioration
of
paper
and
paperboard
products.
It
is
also
used
as
a
paper
coating
preservative
and
paper
adhesive
preservative.
Thus,
dietary
exposure
can
occur
from
its
use
in
pulp
and
paper.

TCMTB
is
used
in
commercial/
institutional
premises,
residential
and
public
access
areas,
as
material
preservatives,
industrial
processes
and
water
systems,
and
as
wood
preservatives.
Examples
of
uses
include
use
in
pulp
and
paper
process
water,
use
for
sapstain
control,
use
as
a
preservative
for
leather
products
and
hides,
textiles,
paints,
adhesives,
wall
paper,
metal
working
fluids,
and
oil
recovery
drill
muds.
Products
containing
TCMTB
are
formulated
as
liquid
ready­
to­
use,
soluble
concentrate,
emulsifiable
liquid,
and
suspo­
emulsion.
The
percentage
of
TCMTB
in
the
various
end­
use
products
ranges
from
1.0%
to
60%.
The
application
rates
used
in
this
assessment
were
the
maximum
application
rates
as
recommended
on
the
product
labels.

6.2
Dietary
(
Food
and
Drinking
Water)
Exposure
and
Risk
Dietary
exposure
may
occur
as
a
result
of
the
use
of
TCMTB
as
a
fungicide
for
seed
treatment,
and
also
from
its
use
as
a
slimicide
and
preservative
in
pulp
and
paper.
The
agricultural
seed
treatment
dietary
risks
include
both
food
and
drinking
water
exposures,
while
the
antimicrobial
dietary
risk
estimates
are
based
exclusively
on
potential
food
exposures.
Details
of
the
dietary
exposure
and
risk
from
its
use
on
seed
treatment
are
in
the
Page
33
of
66
attached
memorandum
from
S.
Ary
February
28,
2006.
In
addition,
estimates
of
TCMTB
exposure
from
use
in
pulp
and
paper
are
presented
in
the
attached
memorandum
from
R.
Quick,
April
4,
2006.
This
section
will
briefly
summarize
of
these
attached
memoranda.

6.2.1
Residue
Profile
As
noted
previously,
the
Risk
Assessment
Review
Committee
(
RARC)
met
and
determined
that
the
interim
residue
of
concern
for
tolerance
expression
and
risk
assessment
is
TCMTB
in/
on
plants.
Additionally,
2­
MBT
and
other
TCMTB
metabolites
were
not
found
at
significant
levels
to
be
considered
residues
of
concern.
Therefore,
only
TCMTB
should
be
considered
a
residue
of
concern
in
plant
commodities.
This
is
a
preliminary
decision
and
additional
confirmatory
metabolism
data
should
be
submitted
in
a
timely
manner.
For
drinking
water,
the
RARC
decided
that
the
residues
of
concern
for
risk
assessment
are
TCMTB
and
2­
MBT.

6.2.2
Dietary
Exposure
for
Agricultural
Uses
As
an
agricultural
pesticide
TCMTB
is
used
as
a
fungicide
for
seed
treatment
of
crops,
bulbs,
and
corn
as
well
as
treatment
of
flowers
and
seed
and
soil
treatment
of
trees.
TCMTB
has
23
tolerances
in
the
40
CFR
180.288
for
use
as
a
fungicide
on
barley
(
grain
and
straw),
sugar
beets
(
roots
and
tops),
corn
(
forage,
grain,
and
stover),
cotton
(
forage
and
undelinted
seed),
oats
(
forage,
grain,
hay,
and
straw),
rice
(
grain
and
straw),
safflower
(
seed),
sorghum
grain
(
forage,
grain,
and
stover),
and
wheat
(
forage,
grain,
hay,
and
straw).
The
permanent
tolerances
for
residues
in
plant
commodities
are
established
at
the
limit
of
quantitation
(
LOQ)
of
0.1
ppm.
Use
on
sorghum
and
corn
are
no
longer
supported
by
the
registrant,
and
thus
are
not
assessed
in
this
report.
The
"
N"
designation,
denoting
"
negligible"
residues
must
be
deleted
from
40
CFR
§
180.288
The
reregistration
of
TCMTB
is
being
supported
by
Bayer
CropScience
(
Bayer)
and
Wilbur­
Ellis
Company
(
Wilbur­
Ellis).
TCMTB
food/
feed
end­
use
products
are
marketed
in
the
United
States
under
the
trade
names
Busan
®
,
Cotguard
®
,
Nusan
®
,
and
Nu­
Flow
®
.
The
Bayer
and
Wilbur­
Ellis
TCMTB
formulations
registered
for
food/
feed
uses
include
emulsifiable
concentrate
(
EC),
soluble
concentrate
(
SC),
and
suspo­
emulsion.
For
food/
feed
uses,
Bayer
is
supporting
TCMTB
use
on
cotton
only,
while
Wilbur­
Ellis
is
supporting
uses
on
barley,
oats,
rice,
wheat,
safflower,
cotton,
and
sugar
beets.
The
technical
registrant
of
TCMTB,
Buckman
Laboratories,
Inc.
(
Buckman),
has
requested
cancellation
of
all
food/
feed
uses.
Bayer
and
Wilbur­
Ellis
will
be
responsible
for
providing
the
Agency
with
the
appropriate
data
needed
to
maintain
the
uses
on
their
product
labels.

Acute
and
chronic
dietary
(
food
and
water)
exposure
assessments
were
conducted
using
the
Dietary
Exposure
Evaluation
Model
software
with
the
Food
Commodity
Intake
Database
(
DEEM­
FCID
 
,
Version
2.03),
which
uses
food
consumption
data
from
the
USDA's
Continuing
Surveys
of
Food
Intakes
by
Individuals
(
CSFII)
from
1994­
1996
and
1998.
The
acute
and
chronic
dietary
risk
assessments
were
conducted
for
all
supported
Page
34
of
66
TCMTB
food
uses.

Drinking
Water
Exposure.
The
Agency
estimated
drinking
water
exposures
for
the
seed
treatment
uses
of
TCMTB.
Details
of
this
modeling
effort
are
provided
in
the
attached
memo
from
J.
Lin,
January
31,
2006,
and
are
summarized
below.

The
drinking
water
analysis
is
based
on
a
derivation
of
estimated
upper
bound
Tier
I
drinking
water
concentrations
from
TCMTB
seed
treatment
uses
based
on
the
FQPA
Index
Reservoir
Screening
Tool
(
FIRST).
Both
TCMTB
and
its
degradates
were
included
in
the
drinking
water
estimates.
A
number
of
conservative
assumptions
were
utilized
as
inputs,
including
the
maximum
rate
of
0.041
lb
ai/
acre,
that
there
are
no
potential
degradation
and
transformation
reactions
and
no
partitioning
between
the
liquid
phase
and
the
solid
phase,
and
that
TCMTB
does
not
sorb
to
the
seed
coat,
but
only
to
the
soil.
In
effect,
this
assumption
provides
conservative
runoff
and
leaching
scenarios.
For
surface
drinking
water,
results
from
FIRST
indicate
that
the
peak
(
acute)
concentration
of
TCMTB
and
its
degradates
is
not
likely
to
exceed
0.94
µ
g/
L
(
ppb),
and
that
the
average
annual
(
chronic)
concentration
is
not
likely
to
exceed
0.67
µ
g/
L.
These
drinking
water
concentrations
were
used
in
the
acute
and
chronic
dietary
risks
for
the
agricultural
uses
of
TCMTB
discussed
below.

Acute
Dietary
Exposure
and
Risk.
The
Agency
conducted
a
conservative
acute
dietary
exposure
assessment
that
incorporated
maximum
theoretical
concentration
factors
for
all
commodities,
existing
tolerance
level
residues,
100%
crop
treated,
and
the
FQPA
Index
Reservoir
Screening
Tool
(
FIRST)
estimated
peak
concentration.
For
acute
exposure
assessments,
individual
one­
day
food
consumption
data
are
used
on
an
individual­
by­
individual
basis.
The
reported
consumption
amounts
of
each
food
item
can
be
multiplied
by
a
residue
point
estimate
and
summed
to
obtain
a
total
daily
pesticide
exposure
for
a
deterministic
exposure
assessment,
or
"
matched"
in
multiple
random
pairings
with
residue
values
and
then
summed
in
a
probabilistic
assessment.
The
resulting
distribution
of
exposures
is
expressed
as
a
percentage
of
the
aPAD.

Acute
dietary
risk
estimates
are
provided
for
the
general
U.
S.
population
and
various
population
subgroups,
with
the
major
emphasis
placed
on
the
exposure
estimates
for
infants
and
children.
This
assessment
concludes
that
for
all
supported
commodities,
the
acute
dietary
risk
estimates
do
not
exceed
HED's
level
of
concern
(
less
than
100%
of
the
aPAD)
at
the
95th
exposure
percentile
for
the
U.
S.
population
(
less
than
1%
of
the
aPAD)
and
all
population
subgroups,
with
the
highest
exposed
population
subgroup
being
children
3­
5
years
old
at
2%
of
the
aPAD.

Chronic
Dietary
Exposure
and
Risk.
The
Agency
conducted
a
conservative
chronic
dietary
exposure
assessment
that
incorporated
maximum
theoretical
concentration
factors
for
all
commodities,
existing
tolerance
level
residues,
100%
crop
treated,
and
the
FIRST
estimated
mean
concentration.

For
chronic
dietary
exposure
assessment,
an
estimate
of
the
residue
level
in
each
food
or
food­
form
(
e.
g.,
orange
or
orange
juice)
on
the
food
commodity
residue
list
is
multiplied
by
the
average
daily
consumption
estimate
for
that
food/
food
form
to
produce
a
Page
35
of
66
residue
intake
estimate.
The
resulting
residue
intake
estimate
for
each
food/
food
form
is
summed
with
the
residue
intake
estimates
for
all
other
food/
food
forms
on
the
commodity
residue
list
to
arrive
at
the
total
average
estimated
exposure.
Exposure
is
expressed
in
mg/
kg
body
weight/
day
and
as
a
percent
of
the
cPAD.
This
procedure
is
performed
for
each
population
subgroup.

As
shown
on
Table
9,
chronic
dietary
risk
estimates
are
provided
for
the
general
U.
S.
population
and
various
population
subgroups,
with
the
major
emphasis
placed
on
the
exposure
estimates
for
infants
and
children.
This
assessment
concludes
that
for
all
supported
commodities,
the
chronic
dietary
risk
estimates
do
not
exceed
HED's
level
of
concern
(
less
than
100%
of
the
cPAD)
for
the
U.
S.
population
(
7%
of
the
cPAD)
and
all
population
subgroups,
with
the
highest
exposed
population
subgroup
being
children
3­
5
years
old
at
17%
of
the
cPAD.

Table
9.
Results
of
Acute
and
Chronic
(
Food
and
Water)
Dietary
Exposure
Analyses
for
TCMTB
Using
DEEM­
FCID.
1,2
Acute
Dietary
(
95th
Percentile)
Chronic
Dietary
Population
Subgroup
Exposure
(
mg/
kg/
day)
%
aPAD3,*
Exposure
(
mg/
kg/
day)
%
cPAD3*

General
U.
S.
Population
0.002430
<
1
0.000888
7
All
Infants
(<
1
year
old)
0.003256
1
0.000994
8
Children
1­
2
years
old
0.004467
2
0.002054
16
Children
3­
5
years
old
0.004581
2
0.002226
17
Children
6­
12
years
old
0.003370
1
0.001625
13
Youth
13­
19
years
old
0.002109
<
1
0.000936
7
Adults
20­
49
years
old
0.001547
<
1
0.000680
5
Adults
50+
years
old
0.001192
<
1
0.000542
4
Females
13­
49
years
old
0.001529
<
1
0.000671
5
1.
The
bolded
values
represent
the
highest
exposed
populations
for
each
percentile.
2.
NA
=
Not
applicable.
3.
%
PAD
=
dietary
exposure
(
mg/
kg/
day)
/
aPAD
or
cPAD,
where
aPAD=
0.25
mg/
kg/
day
for
all
populations;
and
cPAD=
0.013
mg/
kg/
day
for
all
populations.

6.2.3
Dietary
Exposure
for
Antimicrobial
Uses
TCMTB
is
used
as
a
slimicide,
and
paper
coating
preservative
for
controlling
bacteria,
fungi
and
yeasts
that
cause
deterioration
of
paper
and
paperboard
products.
These
Page
36
of
66
uses
are
regulated
by
the
Food
&
Drug
Administration
(
FDA)
(
21
CFR
176.300).
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
FDA
under
21
CFR175.105.
Nevertheless,
the
Agency
estimated
dietary
exposures
to
all
potential
uses
listed
on
the
labels
to
determine
the
total
dietary
exposure
from
all
paper
uses.

The
antimicrobial
uses
being
supported
are
expected
to
have
minimal
impacts
to
drinking
water.
The
registrants
intend
to
cancel
the
use
of
TCMTB
in
Reverse
Osmosis
Water
Systems,
and
Once
Through
Cooling
Towers,
while
the
wood
preservative
use
is
primarily
for
sapstain
control.
Thus,
the
dietary
risks
for
the
antimicrobial
uses
only
consider
potential
food
exposures.

In
the
absence
of
residue
data
for
TCMTB,
the
Agency
estimated
residue
levels
that
may
occur
in
food
that
could
contact
treated
pulp
and
paper
products
(
such
as
a
fast
food
wrapper),
from
the
maximum
application
rates
on
the
labels.
The
Agency
used
an
FDA
model
to
estimate
the
Estimated
Daily
Intake
(
EDI),
along
with
a
number
of
assumptions.
For
the
paper
coating
preservative
use,
the
Agency
assumed
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).
In
addition,
it
was
assumed
that
the
amount
of
food
contacting
the
paper
packaging
is
10
g
of
food/
in2
of
paper,
a
consumption
factor
(
CF)
(
percentage
of
daily
diet
expected
to
contact
paper
coatings)
is
20%
for
paper
coating
and
10%
for
food
packaging
materials
(
slimicide
use),
and
that
there
is
100%
migration
of
TCMTB
from
the
treated
paper
into
food.

The
Agency
estimates
that
TCMTB
food
residues
are
5.6
ppb
for
the
pulp/
paper
slimicide
use,
4
ppb
(
ug/
kg)
for
the
paper
coating
use,
and
7
ppb
(
µ
g/
kg)
for
the
paper
adhesive
preservative
use.
The
Agency
assumed
that
an
adult
consumes
3
kg
of
food
per
day
and
a
child
consumes
1.5
kg
of
food
per
day,
and
used
the
standard
default
assumptions
for
body
weight
(
i.
e.,
70
kg
for
a
male,
60
kg
for
a
female
and
15
kg
for
a
child).
These
daily
estimates
were
conservatively
used
to
assess
both
acute
and
chronic
dietary
risks,
which
are
shown
below
in
Table
10.
In
addition,
the
Agency
estimated
a
total
cumulative
dietary
intake
of
TCMTB
that
could
result
from
simultaneous
exposure
from
the
pulp/
paper
slimicide
use,
the
paper
coating
preservative
use
and
the
paper
adhesive
preservative
use.

As
shown
on
table
10,
the
total
dietary
risk
estimates
are
0.29,
0.33,
0.66%
of
the
aPAD,
and
5.4,
6.4
and
12.8%
of
the
cPAD
for
adult
males,
adult
females
and
children,
respectively
for
TCMTB.
It
is
possible
there
may
be
residues
of
concern
for
2­
mercaptobenzothiazole
(
2­
MBT),
which
is
the
main
mammalian
metabolite
of
TCMTB.
However,
the
Agency
does
not
have
reliable
information
at
this
time.
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).
Page
37
of
66
Table
10.
Summary
of
Dietary
Exposure
and
Risk
for
TCMTB
Antimicrobial
Uses
Acute
Dietary
Chronic
Dietary
Use
Population
Subgroup
Dietary
Exposure
(
mg/
kg/
day)
a
%
aPAD
b
Dietary
Exposure
(
mg/
kg/
day)
a
%
cPAD
b
adult
male
0.00024
0.096
0.00024
1.8
females
(
13­
50
years)
0.00028
0.11
0.00028
2.2
Pulp/
Paper
Slimicide
infants/
children
0.00056
0.22
0.00056
4.3
adult
male
0.00017
0.07
0.00017
1.31
females
(
13­
50
years)
0.0002
0.08
0.0002
1.54
Paper
Coating
Preservative
infants/
children
0.0004
0.16
0.0004
3.08
adult
male
0.00030
0.12
0.00030
2.3
females
(
13­
50
years)
0.00035
0.14
0.00035
2.7
Paper
Adhesive
Preservative
infants/
children
0.0007
0.28
0.0007
5.38
adult
male
0.00071
0.29
0.00071
5.41
females
(
13­
50
years)
0.00083
0.33
0.00083
6.44
Cumulative
infants/
children
0.0017
0.66
0.0017
12.8
NA=
not
applicable
a­­
acute
and
chronic
exposure
analysis
based
on
body
weights
of
70
kg,
60
kg,
and
15
kg
for
adult
males,
females
and
children,
respectively.
b­­
%
PAD
=
dietary
exposure
(
mg/
kg/
day)
/
aPAD
or
cPAD,
where
aPAD=
0.25
mg/
kg/
day
for
all
populations;
and
cPAD=
0.013
mg/
kg/
day
for
all
populations.

6.3
Residential
Exposure/
Risk
Pathway
Details
of
the
residential
exposure
assessment
can
be
found
within
the
companion
memorandum
(
memorandum
from
S.
Mostaghimi,
April
2006).
A
summary
of
the
residential
assessment
is
presented
below.

6.3.1
Residential
Handler
Exposure
Scenarios
TCMTB
is
an
antimicrobial
ingredient
used
as
a
materials
preservative
in
residential
and
public
access
areas.
It
is
used
as
a
wood
preservative
primarily
to
control
sapstain,
as
a
preservative
in
textiles/
leather,
carpets,
and
paints.
The
following
representative
residential
handler
scenarios
were
evaluated:
Page
38
of
66
(
1)
painting
with
an
airless
sprayer;
and
(
2)
painting
with
a
brush/
roller.

TCMTB
have
a
large
number
of
use
patterns
that
are
difficult
to
completely
capture
in
this
assessment.
As
such,
the
Agency
has
selected
representative
scenarios
for
each
use
site
that
are
believed
to
be
representative
of
the
vast
majority
of
TCMTB
uses,
based
on
end­
use
product
application
methods
and
use
amounts.

Exposure
Data
and
Assumptions
There
are
no
chemical­
specific
exposure
data
to
assess
paint
applications
with
a
brush,
roller,
or
airless
sprayer.
Dermal
and
inhalation
exposures
were
assessed
for
these
scenarios
using
the
Pesticides
Handler
Exposure
Database
(
PHED)
Version
1.1
values
found
in
the
Residential
Exposure
SOPs
(
U.
S.
EPA,
1997a,
2001).
The
dermal
and
inhalation
exposures
from
these
techniques
have
been
normalized
by
the
amount
of
active
ingredient
handled
and
reported
as
unit
exposures
(
UE)
expressed
as
mg/
lb
ai
handled.

In
addition,
product
label
maximum
application
rates,
related
use
information,
and
Agency
standard
values
were
used
to
assess
residential
handler
exposures.
For
example,
it
was
assumed
that
a
resident
applies
15
gallons
of
paint
per
day
using
an
airless
sprayer,
and
2
gallons
of
paint
per
day
using
a
brush/
roller.
The
residential
handler
scenarios
are
assumed
to
be
of
short­
term
duration
(
1­
30
days)

Risk
Characterization
A
summary
of
the
residential
handler
exposures
and
risk
are
presented
in
Table
11.
The
non­
cancer
risk
estimates
are
expressed
in
terms
of
the
MOE.
For
residential
handlers
that
handle
products
containing
TCMTB,
short­
term
dermal
MOEs
were
10
and
25
for
airless
sprayer
and
paint
brush
applications
methods,
respectively
and
thus
are
of
risk
concern
(
i.
e.,
below
the
target
MOE
of
100).
The
inhalation
MOEs
are
not
of
risk
concern
as
the
MOEs
were
600
and
13,000,
respectively.

Because
the
dermal
and
inhalation
endpoints
have
similar
toxicological
effects
on
body
weight
they
should
be
combined.
As
shown
on
Table
11,
the
total
MOEs
are
less
than
100
for
both
the
airless
sprayer
and
paintbrush/
roller
methods
of
application.
Thus
these
risk
estimates
exceed
the
Agency's
level
of
concern,
mostly
because
of
the
dermal
route
of
exposure.
These
risks
are
conservative
because
they
assume
an
individual
will
handle
15
gallons
of
paint
using
an
airless
sprayer
and
2
gallons
of
paint
via
paintbrush
in
one
day.
Page
39
of
66
Table
11
Estimates
of
Exposures
and
Risks
to
Residential
Handlers
of
TCMTB
(
Short­
Term
Duration)

Scenario
Dermal
Dose
(
mg/
kg/
day)
a
Inhalation
Dose
(
mg/
kg/
day)
b
Dermal
MOEc
(
Target
MOE 
100)
Inhalation
MOEd
(
Target
MOE 
100)
Total
MOE
(
Target
 
100)

(
1)
Airless
Sprayer
2.54
0.0267
10
600
9.8
(
2)
Paintbrush/
Roller
0.986
0.00122
25
13,000
25
a
Dermal
Dose
(
mg/
kg/
day)
=
[
Unit
Dermal
Exposure
(
mg/
lb
ai)
*
Use
Rate
(
lb
ai/
lb
product
or
lb
ai/
gal
product)
*
Amount
Handled
per
Day
(
lb
product/
day)]
/
Body
Weight
(
kg).
b
Inhalation
Dose
(
mg/
kg/
day)
=
[
Unit
Inhalation
Exposure
(
mg/
lb
ai)
*
Use
Rate
(
lb
ai/
lb
product
or
lb
ai/
gal
product)
*
Amount
Handled
per
Day
(
lb
product/
day)*
inhalation
absorption
(
1.0)]
/
Body
Weight
(
kg)
c
Dermal
MOE
=
Dermal
NOAEL
(
mg/
kg/
day)
/
Dermal
Dose
(
mg/
kg/
day).
Where
the
NOAEL
is
25
mg/
kg/
day
from
the
subchronic
rat
dermal
toxicity
study.
d
Inhalation
MOE
=
Inhalation
NOAEL
(
mg/
kg/
day)
/
Inhalation
Dose
(
mg/
kg/
day).
Where
the
inhalation
NOAEL
of
16
mg/
kg/
day
is
from
an
oral
rabbit
developmental
study.
In
the
absence
of
data,
inhalation
absorption
is
assumed
to
be
equivalent
to
oral
absorption
6.3.2
Postapplication
Residential
Exposure
Residential
postapplication
exposures
result
when
bystanders
(
adults
and
children)
come
in
contact
with
TCMTB
in
areas
where
pesticide­
treated
end­
use
products
have
recently
been
applied
(
e.
g.,
treated
textiles,
leather
products,
and
carpets),
or
when
children
incidentally
ingest
the
pesticide
residues
through
mouthing
the
treated
end
products/
treated
articles
(
i.
e.,
hand­
to­
mouth
or
object­
to­
mouth
contact).

For
the
purposes
of
this
screening
level
assessment,
postapplication
scenarios
have
been
developed
that
encompass
multiple
products,
but
still
represent
a
high
end
exposure
scenario
for
all
products
represented.
Residential
exposure
to
TCMTB­
treated
wood
products
is
expected
to
be
minimal
because
the
wood
preservative
use
is
primarily
for
sapstain
control.
Representative
postapplication
scenarios
assessed
include:

°
contacting
treated
carpets
(
dermal
and
incidental
oral
exposure
to
children),
°
wearing
treated
clothing/
leather
products
(
dermal
exposure
to
adults
and
children),
and
°
mouthing
treated
textiles
such
as
clothing/
blankets/
leather
products
(
incidental
oral
exposure
to
children).

Exposure
Data
and
Assumptions
Typically,
most
products
used
in
a
residential
setting
result
in
exposures
occurring
over
a
short­
term
time
duration
(
1
 
30
days).
For
treated
textiles/
leather
products,
the
Page
40
of
66
Agency
believes
these
exposures
are
primarily
short­
term
because
residents
are
assumed
to
be
exposed
to
treated
textiles
with
varying
active
ingredients,
not
exclusively
TCMTB
treated
textiles.
However,
if
the
products
are
used
on
a
routine
basis
(
i.
e.,
once
a
week,
or
impregnated
into
carpets
as
a
materials
preservative)
and
the
active
ingredient
has
a
long
indoor
half­
life,
exposures
may
occur
over
an
intermediate­
term
time
duration
(
30
days
 
6
months).
At
this
time,
AD
does
not
have
residue
dissipation
data
or
reliable
use
pattern
data,
including
the
frequency
and
duration
of
use
of
antimicrobial
products
in
the
residential
setting.
Even
though
AD
does
not
believe
that
the
use
patterns
of
many
residential
products
result
in
intermediate­
term
exposure,
they
are
assessed
to
provide
an
upper
bound
estimate
of
exposure.
It
should
be
noted
that
because
the
toxicological
endpoints
are
identical
for
short­
and
intermediate­
term
durations,
the
risk
estimates
are
essentially
identical
for
both
short­
and
intermediate­
term
exposure
durations.

A
number
of
conservative
assumptions
were
used
in
assessing
postapplication
risks
including
maximum
application
rate
from
the
label.
In
addition
quantities
handled/
treated
were
estimated
based
on
information
from
various
sources,
including
the
Draft
Standard
Operating
Procedures
(
SOPs)
for
Residential
Exposure
Assessments
(
USEPA
2000,
2001)
and
standard
AD
Residential
SOP
assumptions.
In
certain
cases,
no
standard
values
were
available
for
some
scenarios.
Assumptions
for
these
scenarios
were
based
on
AD
estimates
and
could
be
further
refined
from
input
from
affected
sectors.
In
the
absence
of
data,
for
both
the
textile/
treated
leather
product
scenarios,
it
was
assumed
that
either
100%
or
5%
of
TCMTB
could
transfer
and
be
available
for
dermal
contact.
The
Agency
will
require
data
to
confirm
the
actual
transfer
factor
of
TCMTB.

Risk
Characterization
A
summary
of
the
residential
postapplication
exposures
and
risks
are
presented
on
Table
12.
The
non­
cancer
risk
estimates
are
expressed
in
terms
of
the
MOE.
The
target
MOEs
are
>
100
for
dermal
and
incidental
oral
exposures.
Because
the
toxicological
endpoints
are
similar
for
dermal
and
incidental
oral
exposures,
the
Agency
calculated
a
total
MOE
for
children.

Dermal
Risks.
The
short­
and
intermediate­
term
MOEs
for
dermal
contact
with
treated
clothing/
leather
products
are
of
concern
for
both
young
children
and
adults
(
MOEs
are
<
1
assuming
a
100%
transfer
factor;
MOEs
are
<
10
assuming
a
5%
transfer
factor).
In
addition,
the
MOE
is
of
concern
for
young
children
crawling
on
treated
carpets
(
MOE=
2).
The
Agency
requests
confirmatory
data
for
a
TCMTB
transfer
factor
from
clothing/
leather
products
and
carpets.
In
addition,
it
should
be
noted
that
TCMTB
is
a
dermal
sensitizer,
and
thus,
there
is
potential
for
adverse
dermal
allergic
reactions
from
direct
skin
contact
of
treated
textiles.
The
Agency
intends
to
consider
these
effects
in
the
labeling
of
pesticide
products
containing
TCMTB,
and
request
additional
dermal
toxicity
data
on
the
diluted
end­
use
formulated
product.

Incidental
Oral
Risks.
The
short­
and
intermediate­
term
MOE
for
incidental
ingestion
of
treated
carpets
exceeds
the
Agency's
level
of
concern
(
MOE=
4.2,
while
the
target
MOE
is
>
100),
and
thus
is
of
risk
concern.
In
addition,
the
short­
term
oral
MOE
Page
41
of
66
for
children
mouthing
treated
textiles/
leather
products
is
of
risk
concern
(
MOE=
21
compared
to
target
MOE>
100).

Table
12
Summary
of
Short­
and
Intermediate­
Term
Residential
Postapplication
Exposures
and
Risks
Dose
a
(
mg/
kg/
day)
MOEb
(
Target
MOE>
100)
Scenario
Child
Adult
Child
Adult
Dermal
Exposure
Treated
carpets
15.6
NA
2
NA
4.3
(
5%
transfer)
2.7
(
5%
transfer)
5.8
9.1
Treated
clothing/
leather
products
86
(
100%
transfer)
55
(
100%
transfer)
<
1
<
1
Incidental
Oral
Exposure
Treated
carpets
3.81
NA
4.2
NA
Treated
clothing/
leather
products
0.758
NA
21
NA
Total
MOE
Risk
Estimate
NA
<
1
c
NA
NA=
Not
applicable
a
Dose
calculations
for
each
scenario
above
are
outlined
in
the
attached
Occupational/
Residential
Assessment
(
memo
from
S.
Mostaghimi,
February
2006).
b
MOE=
NOAEL
(
mg/
kg/
day)
/
PDR
(
mg/
kg/
day).
Oral
NOAEL
is
16
mg/
kg/
day;
dermal
NOAEL
is
25
mg/
kg/
day.
c
Total
MOE
includes
carpet
(
dermal
and
oral)
and
clothing
(
dermal
and
oral)
exposures
using
the
exposure
estimates
based
on
5%
residue
transfer.

Total
Dermal
and
Incidental
Risk
Estimates.
As
shown
on
Table
12,
the
total
MOE
for
children
who
may
contact
treated
carpet
and
clothing
is
<
1,
and
thus
is
of
risk
concern,
primarily
because
the
individual
scenarios
are
already
of
risk
concern.

7.0
AGGREGATE
RISK
ASSESSMENTS
AND
RISK
CHARACTERIZATION
In
order
for
a
pesticide
registration
to
continue,
it
must
be
shown
that
the
use
does
not
result
in
"
unreasonable
adverse
effects
on
the
environment".
Section
2
(
bb)
of
FIFRA
defines
this
term
to
include
"
a
human
dietary
risk
from
residues
that
result
from
a
use
of
a
pesticide
in
or
on
any
food
inconsistent
with
standard
under
section
408..."
of
FFDCA.
As
mandated
by
the
FQPA
amendments
to
FIFRA
and
the
Federal
Food,
Drug
and
Cosmetic
Act
(
FFDCA),
the
Agency
must
consider
total
aggregate
exposure
from
food,
drinking
water
and
residential
sources
of
exposure
to
TCMTB.
Aggregate
exposure
is
the
total
exposure
to
a
single
chemical
(
or
its
residues)
that
may
occur
from
dietary
(
i.
e.,
food
and
drinking
water),
residential,
and
other
non­
occupational
sources,
and
from
plausible
exposure
routes
(
oral,
dermal,
and
inhalation).

Typically,
aggregate
risk
assessments
are
conducted
for
acute
(
1
day),
short­
term
(
1­
30
days),
intermediate­
term
(
1­
6
months)
and
chronic
(
6
months
to
lifetime)
exposures.
Short­
and
intermediate­
term
aggregate
assessments
were
not
conducted
because
all
of
the
Page
42
of
66
residential
uses
previously
evaluated
have
risks
of
concern
(
i.
e.,
handler
applying
paint,
children
playing
on
treated
carpets,
and
adults
and
children
wearing
treated
textiles/
leather
products).
Thus,
the
short­
and
intermediate­
term
aggregate
assessments
would
also
show
risks
of
concern.

The
Agency
conducted
both
acute
and
chronic
aggregate
assessments,
which
considered
food
and
drinking
water
exposures
from
the
registered
agricultural
and
antimicrobial
uses.
Because
there
are
no
long­
term
residential
exposures,
the
chronic
aggregate
assessment
only
considered
food
and
drinking
water.

In
performing
aggregate
exposure
and
risk
assessments,
the
Office
of
Pesticide
Programs
has
published
guidance
outlining
the
necessary
steps
to
perform
such
assessments
(
General
Principles
for
Performing
Aggregate
Exposure
and
Risk
Assessments,
November
28,
2001;
available
at
http://
www.
epa.
gov/
pesticides/
trac/
science/
aggregate.
pdf
).
Steps
for
deciding
whether
to
perform
aggregate
exposure
and
risk
assessments
are
listed,
which
include:
identification
of
toxicological
endpoints
for
each
exposure
route
and
duration;
identification
of
potential
exposures
for
each
pathway
(
food,
water,
and/
or
residential);
reconciliation
of
durations
and
pathways
of
exposure
with
durations
and
pathways
of
health
effects;
determination
of
which
possible
residential
exposure
scenarios
are
likely
to
occur
together
within
a
given
time
frame;
determination
of
magnitude
and
duration
of
exposure
for
all
exposure
combinations;
determination
of
the
appropriate
technique
(
deterministic
or
probabilistic)
for
exposure
assessment;
and
determination
of
the
appropriate
risk
metric
to
estimate
aggregate
risk.

Acute
Aggregate
Risk.
The
acute
aggregate
assessment
considers
the
95th
percentile
dietary
exposure
(
food
and
drinking
water)
from
the
agricultural
seed
treatment
uses,
as
well
as
the
acute
dietary
exposure
(
food
only)
from
the
antimicrobial
uses
in
pulp
and
paper.
As
shown
on
Table
13,
the
acute
dietary
aggregate
risk
is
2.5%
of
the
aPAD
for
children,
while
for
adults
it
is
<
1.3%
of
the
aPAD.
These
risk
estimates
are
below
the
Agency's
level
of
concern.

Table
13
Summary
of
Acute
Aggregate
Risk
Estimates
for
TCMTB
Dose
a
(
mg/
kg/
day)
%
aPADb
Exposure
Scenario
Child
(
15
kg)
Adult
Child
(
15
kg)
Adult
Dietary
Exposure
Agricultural
Seed
treatment
(
Food
and
Water)
0.004581
0.00243
1.8%
<
1%

Antimicrobial
Uses
Total
Pulp/
Paper/
Adhesive
(
Food)
0.0017
0.00083
0.66%
0.33
Total
Aggregate
Dose
and
Risk
0.00628
0.00328
2.5%
<
1.3%

NA=
Not
applicable
(
a)
Acute
dietary
exposure
for
females
13­
50
years
for
antimicrobials
uses.
Page
43
of
66
(
b)
%
aPAD
=
dietary
exposure
(
mg/
kg/
day)
/
aPAD,
where
aPAD
­=
0.25
mg/
kg/
day
for
all
populations.

Chronic
Aggregate
Risk.
The
chronic
aggregate
assessment
considers
average
dietary
exposure
(
food
and
drinking
water)
from
the
agricultural
seed
treatment
uses,
as
well
as
dietary
exposure
(
food
only)
from
the
antimicrobial
uses
in
pulp
and
paper.
As
shown
on
Table
14,
the
chronic
dietary
aggregate
risk
is
40%
of
the
cPAD
for
children,
while
for
adults
it
is
13.4%
of
the
cPAD.
These
risk
estimates
are
below
the
Agency's
level
of
concern.

Table
14
Summary
of
Chronic
Aggregate
Risk
Estimates
for
TCMTB
Dose
a
(
mg/
kg/
day)
%
cPADb
Exposure
Scenario
Child
(
15
kg)
Adult
Child
(
15
kg)
Adult
Dietary
Exposure
Agricultural
Seed
treatment
(
Food
and
Water)
0.002226
0.000888
17%
7%

Antimicrobial
Uses
Total
Pulp/
Paper/
Adhesive
(
Food)
0.0017
0.00083
12.8%
6.44
Total
Aggregate
Dose
and
Risk
0.003926
0.001718
30%
13.4%

NA=
Not
applicable
(
c)
Chronic
dietary
exposure
for
females
13­
50
years
for
antimicrobials
uses.
(
d)
%
cPAD
=
dietary
exposure
(
mg/
kg/
day)
/
cPAD,
where
cPAD
­=
0.013
mg/
kg/
day
for
all
populations.

8.0
CUMULATIVE
EXPOSURE
AND
RISK
Another
standard
of
section
408
of
the
FFDCA
which
must
be
considered
in
making
an
unreasonable
adverse
effect
determination
is
that
the
Agency
considers
"
available
information"
concerning
the
cumulative
effects
of
a
particular
pesticide's
residues
and
"
other
substances
that
have
a
common
mechanism
of
toxicity."

For
the
purposes
of
this
tolerance
action,
therefore,
EPA
has
not
assumed
that
TCMTB
has
a
common
mechanism
of
toxicity
with
other
substances.
For
information
regarding
EPA's
efforts
to
determine
which
chemicals
have
a
common
mechanism
of
toxicity
and
to
evaluate
the
cumulative
effects
of
such
chemicals,
see
the
policy
statements
released
by
EPA's
Office
of
Pesticide
Programs
concerning
common
mechanism
determinations
and
procedures
for
cumulating
effects
from
substances
found
to
have
a
common
mechanism
on
EPA's
website
at
http://
www.
epa.
gov/
pesticides/
cumulative/.

9.0
OCCUPATIONAL
EXPOSURE
AND
RISK
The
Agency
has
assessed
the
exposures
and
risks
to
occupational
workers
that
Page
44
of
66
handle
TCMTB
for
both
agricultural
uses
(
i.
e.,
seed
treatment)
(
memorandum
from
C.
Smith,
April
2006)
and
antimicrobial
uses
(
i.
e.,
materials
preservation,
metal
working
fluids,
wood
preservation
etc)
(
memorandum
from
S.
Mostaghimi
April
2006).
This
section
summarizes
the
results
of
the
occupational
exposure
assessment.

9.1
Agricultural
Uses
(
Seed
Treatment)

Based
on
examination
of
product
labels
describing
uses
for
the
product,
it
has
been
determined
that
exposure
to
handlers
can
occur
in
a
variety
of
occupational
settings.
Additionally,
postapplication
exposures
are
likely
to
occur
in
these
settings.
The
representative
scenarios
selected
by
the
Agency
for
assessment
were
evaluated
using
maximum
application
rates
as
recommended
on
the
product
labels
for
TCMTB.

Occupational
Handlers.
The
Agency
has
determined
that
there
is
potential
for
dermal
and
inhalation
worker
exposure
to
TCMTB
from
handling
TCMTB
products
during
the
seed
treating
process
(
both
commercial
and
on­
farm)
and
a
potential
for
postapplication
worker
exposure
from
handling
seed
previously
treated
with
TCMTB.
As
a
result,
risk
assessments
have
been
completed
for
occupational
handler
scenarios
as
well
as
occupational
postapplication.
The
occupational
exposure
scenarios
and
estimated
risks
are
presented
on
Table
15.

Exposure
data
used
for
the
TCMTB
seed
treatment
assessment
are
taken
primarily
from
HED's
recently
developed
seed
treatment
standard
operating
procedure
(
SOPs
for
Seed
Treatment,
6/
1/
03)
and
also
are
based
on
professional
judgment.
The
seed
treatment
SOP
contains
representative
scenarios
for
worker
exposure
associated
with
seed
treatment
facilities
and
planting
treated
seed.
The
data
contained
in
the
SOP
are
mostly
generated
by
industry
sources.
Exposure
estimates
are
from
actual
seed
treatment
studies
and
are
based
on
exposure
factors
associated
with
occupational
handler
scenarios
(
i.
e.,
commercial
seed
treatment,
on­
nursery
seed
treatment,
planting
of
treated
seed).
Eight
seed
treatment
studies
were
used
in
developing
the
SOP.
Given
the
high
level
of
variance
in
the
data,
multiple
statistical
analyses
were
undertaken
to
help
ensure
derivation
of
a
statistically
sound
exposure
value
for
the
different
scenarios
evaluated.
For
all
selected
seed
treatment
studies,
replicates
were
combined
into
sets
of
equivalent
job
functions.
This
process
resulted
in
four
categories
of
commercial
seed
treatment
activities
(
loader/
applicator,
sewer,
bagger,
and
multiple
activities),
and
two
categories
for
on­
nursery
activities
(
treater
and
planter).

The
Agency
evaluated
occupational
risks
to
workers
that
use
TCMTB
as
a
fungicide
for
treating
seeds
in
commercial
and
on­
farm
settings.
The
duration
of
exposure
is
expected
to
be
short­
or
intermediate­
term
(
1
day
to
6
months).
For
commercial
seed
treatment,
all
individual
dermal
MOEs
met
or
exceeded
the
target
MOE
of
at
some
level
of
mitigation,
and
thus
are
not
of
concern.
However,
a
few
of
the
individual
inhalation
MOEs
did
not
meet
or
exceed
the
target
MOE
of
100.
Risks
remain
a
concern
for
3
scenarios
even
with
maximum
inhalation
risk
mitigation
of
a
respirator
or
engineering
controls:

$
Multiple
activities
for
barley,
cotton,
oat,
rice,
safflower,
and
wheat
seeds
(
inhalation
MOEs=
24­
37
with
90%
protection
from
a
respirator).
Page
45
of
66
For
commercial
seed
treatment,
most
of
the
combined
dermal
and
inhalation
risks
were
not
of
risk
concern.
A
few
scenarios
did
not
meet
the
target
MOE
of
100,
even
with
maximum
risk
mitigation.
Risks
remain
a
concern
for
4
scenarios
even
with
maximum
risk
mitigation:

$
Loader/
applicator
for
safflower;
and
$
Multiple
activities
for
barley,
cotton,
oat,
rice,
safflower,
and
wheat
seeds.

Table
15.
Estimated
Worker
Exposure
and
Risk
from
Commercial
Seed
Treatment
Short­
and
Intermediate­
term
Risk
Estimates
Crop
Exposure
Scenario
Application
Rate
(
lb
ai/
100
lb)
a
Amount
Handled
per
Day
(
lb
ai/
day)
b
Dermal
MOE
(
Target
MOE 
100)
Inhalation
MOE
(
Target
MOE 
100)
Total
MOE
c
(
Target
MOE 
100)
Level
of
Mitigationc
Loader/
Applic
ator
410
180
120
SL,
G+
90%
R
Sewer
1500
130
120
SL
+
80%
R
Bagger
1000
190
160
SL
+
80%
R
Barley,
Oat,
Rice,
Wheat
Seeds
Multiple
Activities
0.026
187
220
37
32
SL,
G+
90%
R
Loader/
Applic
ator
370
160
110
SL,
G+
90%
R
Sewer
1400
120
110
SL
+
80%
R
Bagger
920
170
140
SL
+
80%
R
Cotton
Seeds
Multiple
Activities
0.13
208
200
34
29
SL,
G+
90%
R
Loader/
Applic
ator
260
110
78
SL,
G+
90%
R
Sewer
960
110
140
SL
+
90%
R
Bagger
650
160
170
SL
+
90%
R
Safflower
Seeds
Multiple
Activities
0.041
294
140
24
20
SL,
G+
90%
R
Loader/
Applic
ator
2100
460
380
SL,
G+
80%
R
Sewer
7800
130
130
SL
+
NR
Bagger
5300
190
180
SL
+
NR
Sugar
Beet
Seeds
Multiple
Activities
0.041
36
1200
190
170
SL,
G+
90%
R
ND
=
No
Data;
NF
=
Not
Feasible;
NR=
No
respirator
a
Application
rates
are
the
maximum
application
rates
determined
from
EPA
registered
labels
for
TCMTB
b
Amount
handled
per
day
calculated
from
the
maximum
application
rate
and
the
lbs
of
seed
treated
or
planted/
day
and:
for
barley,
rice,
safflower,
and
wheat
seed
­
718000
lb/
day;
for
cotton
seed
 
160000
lb/
day;
and
sugar
beet
seed
 
88000
lb/
day.
c
Baseline
Dermal:
Long­
sleeve
shirt,
long
pants,
no
gloves.
Baseline
Inhalation:
no
respirator.
SL,
G
=
Single
layer
w/
gloves
is
baseline
attire
plus
chemical­
resistant
gloves.
DL,
G
=
Double
layer
w/
gloves
is
coveralls
worn
over
long­
sleeve
shirt
and
long
pants,
plus
80%
R
=
80%
Respirator
is
filtering
facepiece
dust/
mist
respirator
(
that
provides
an
80%
protection
factor).
90%
R
=
90%
Respirator
is
half­
face
dust/
mist
respirator
(
that
provides
a
90%
protection
factor).
Eng
Control
=
Engineering
control
is
closed
mixing/
loading
system,
elastomeric
facepiece
respirator
with
dust/
mist
filters.
Page
46
of
66
Postapplication
Exposure
and
Risk.
For
all
of
the
on­
nursery
seed
treatment
scenarios,
individual
dermal
and
inhalation
MOEs
met
or
exceeded
the
required
uncertainty
factor
of
100
at
some
level
of
risk
mitigation,
and
thus
are
not
of
risk
concern.
For
on­
farm
seed
treatment
scenarios,
all
combined
dermal
and
inhalation
risks
also
met
or
exceeded
the
target
MOE
of
100
at
some
level
of
risk
mitigation.

Table
16.
Estimated
Worker
Exposure
and
Risk
from
On­
Nursery
Seed
Treatment
(
Postapplication)

Short­
and
Intermediate­
term
Risk
Estimates
Crop
Acres
treated/
day
App
Rate
(
lb
ai/
100
lb)
a
Amount
Handled
per
dayb
(
lb
ai/
day)
Inhalation
MOE
(
Target
MOE 
100)
Dermal
MOE
SL
w/
gloves
(
Target
MOE 
100)
Total
MOE
(
Target
MOE 
100)
Level
of
Mitigation
LOADING/
APPLYING
LIQUID
SEED
TREATMENTS
Cotton
125
0.051
0.64
NDd
LOADING/
PLANTING
PREVIOUSLY
TREATED
SEEDS
Barley
35
0.026
0.64
360
7700
350
SL,
G
+
NR
Beet;
Sugar
80
0.041
0.26
1300
27000
1200
SL,
G
+
NR
Cotton
200
0.13
4.68
350
1500
280
SL,
G
+
80%
R
Oats
200
0.026
6.66
250
1100
200
SL,
G+
80%
R
Rice
200
0.026
7.80
210
900
170
SL,
G+
80%
R
Safflower
80
0.41
3.28
500
2100
400
SL,
G
+
80%
R
Wheat
200
0.026
7.80
210
900
170
SL,
G+
80%
R
ND
=
No
Data;
NF
=
Not
Feasible;
NR
=
no
respirator
SL,
G
=
Single
layer
w/
gloves
is
baseline
attire
plus
chemical­
resistant
gloves.
80%
R
=
80%
Respirator
is
filtering
facepiece
dust/
mist
respirator
(
that
provides
an
80%
protection
factor).
90%
R
=
90%
Respirator
is
half­
face
dust/
mist
respirator
(
that
provides
a
90%
protection
factor).
a
Application
rates
are
the
maximum
application
rates
determined
from
EPA
registered
labels
for
TCMTB
b
Amount
handled
per
day
calculated
from
the
acres
treated/
day
and
the
maximum
lb
of
seed
planted
per
acre.
c
On­
nursery
seed
treatment
with
liquid
formulations
is
generally
done
with
automated
equipment,
essentially
miniature
versions
of
commercial
treaters.

9.2
Antimicrobial
Uses
TCMTB
is
used
in
commercial/
institutional
premises,
as
a
material
preservative,
in
industrial
processes
and
water
systems,
and
as
a
wood
preservative.
Examples
of
registered
uses
include
use
in
pulp
and
paper
process
water,
use
for
sapstain
control,
use
as
a
preservative
for
leather
products
and
hides,
textiles,
paints,
adhesives,
wall
paper,
metal
working
fluids,
and
oil
recovery
drill
muds.
Products
containing
TCMTB
are
formulated
as
liquid
ready­
to­
use,
soluble
concentrate,
emulsifiable
liquid
and
suspo­
emulsion.
The
percentage
of
TCMTB
in
the
various
end­
use
products
ranges
from
1.0%
to
60%.

Based
on
examination
of
product
labels
describing
uses
for
the
product,
it
has
been
determined
that
exposure
to
handlers
can
occur
in
a
variety
of
occupational
settings.
Additionally,
postapplication
exposures
are
likely
to
occur
in
these
settings
from
the
metal
working
fluid
use
and
wood
preservation
uses.
Representative
scenarios
selected
for
Page
47
of
66
evaluation
based
on
the
use
sites
and
maximum
application
rates
as
recommended
on
the
product
labels
for
TCMTB.
To
assess
the
handler
risks,
AD
used
surrogate
unit
exposure
data
from
both
the
proprietary
Chemical
Manufacturers
Association
(
CMA)
antimicrobial
exposure
study
and
the
Pesticide
Handlers
Exposure
Database
(
PHED).

Occupational
Handlers.
The
Agency
has
determined
that
there
is
potential
for
dermal
and
inhalation
worker
exposure
to
TCMTB
in
occupational
settings
such
as
commercial/
institutional
premises,
and
industrial
processes
and
water
systems.

For
the
occupational
handler
dermal
and
inhalation
risk
assessment,
the
MOEs
were
above
the
target
MOE
of
100
for
short­
and
intermediate­
term
durations
at
single
layer
PPE
for
open
pouring
or
through
the
use
of
mitigation
(
e.
g.,
metering
pumps)
for
all
scenarios
except
for
the
following
scenarios
listed
below.
It
should
be
noted
that
the
baseline
(
ungloved)
dermal
MOEs
for
material
preservation
of
paints,
textiles,
adhesives,
and
metalworking
fluid
were
calculated
using
unit
exposure
values
from
the
cooling
tower
CMA
data
set
because
baseline
dermal
unit
exposures
are
not
available
for
preservative
or
metal
fluid
categories.

 
Paint
Application
 
Airless
Sprayer:
ST/
IT
Dermal
MOE
=
6.1
(
ungloved)
and
17
(
gloved).
 
Paint
Application
 
Paintbrush:
ST/
IT
Dermal
MOE
=
30
(
ungloved)
and
97
(
gloved)
 
Paint
Preservation
 
Liquid
Pour:
ST/
IT
Dermal
MOE
=
1
(
ungloved)
 
Paint
Preservation
 
Liquid
Pump:
ST/
IT
Dermal
MOE
=
26
(
ungloved)
 
Textile
Preservation
 
Liquid
Pour:
ST/
IT
Dermal
MOE
=
<
1
(
ungloved)
 
Textile
Preservation
 
Liquid
Pump:
ST/
IT
Dermal
MOE
=
64
(
ungloved)
 
Cutting
Fluid
Preservation
 
Liquid
Pour:
ST/
IT
Dermal
MOE
=
11
(
ungloved)
 
Pulp
and
Paper
 
Liquid
Pump:
ST/
IT
Dermal
MOE
=
5
(
ungloved)

Table
17
Short
and
Intermediate­
Term
Risks
Associated
with
Occupational
Handlers
ST/
IT
MOE
c
(
Target
MOE
 
100)
Exposure
Scenario
Method
of
Application
Application
Rate
(%
a.
i.
by
weight)
Quantity
Handled/
Treated
per
day
Baseline
Dermala
PPE­
Glove
Dermal
b
Inhalation
TOTAL
MOE
(
dermal
and
inhalation)

Airless
Sprayer
500
lb/
day
6.1
17
180
16
Paint
Application
Paintbrush
50
lb/
day
30
97
5,300
95
Liquid
Pour
2,000
lb/
day
1.2
430
11,000
414
Paint
Preservation
Liquid
Pump
0.015
a.
i.
weight
fraction
10,000
lb/
day
26
1900
19,000
1,727
Liquid
Pour
<
1
220
5,400
211
Textiles/
Leather
Products
Liquid
Pump
0.006
a.
i.
weight
fraction
10,000
lb/
day
64
4,600
46,000
4,182
Liquid
Pour
11
3,000
42,000
2,800
Cutting
Fluid
Liquid
Pump
0.00125
a.
i.
weight
fraction
2,502
lb/
day
1,200
1,800
1.00x105
1,768
ST
=
45.9
lb/
day
ST
=
1000
ST
=
380,000
ST
=
9.40x10­
6
365,235
Drilling
Fluids
Liquid
Pour
0.00075
a.
i.
weight
fraction
IT
=
22.9
lb/
day
IT
=
2,000
IT
=
7.60x105
IT
=
1.90x107
730,769
Page
48
of
66
Table
17
Short
and
Intermediate­
Term
Risks
Associated
with
Occupational
Handlers
ST/
IT
MOE
c
(
Target
MOE
 
100)
Exposure
Scenario
Method
of
Application
Application
Rate
(%
a.
i.
by
weight)
Quantity
Handled/
Treated
per
day
Baseline
Dermala
PPE­
Glove
Dermal
b
Inhalation
TOTAL
MOE
(
dermal
and
inhalation)

Pulp
and
Paper
Liquid
Pump
1,000,000
lb/
day
5
510
5,600
467
Liquid
Pour
90
lb/
day
43,000
21,000
3.10x106
20.858
Small
Process
Water
Systems/
Cooling
Tower
Liquid
Pump
0.000009
a.
i.
weight
fraction
180,000
lb/
day
2,400
13,000
1.60x105
12,023
ST
=
short­
term;
IT
=
intermediate­
term
a
Baseline
Dermal:
Long­
sleeve
shirt,
long
pants,
no
gloves.
b
PPE
Dermal
with
gloves:
baseline
dermal
plus
chemical­
resistant
gloves.
c
MOE
=
NOAEL
(
mg/
kg/
day)
/
Absorbed
Daily
Dose
[
Where
ST/
IT
NOAEL
=
25
mg/
kg/
day
for
dermal
and
16
mg/
kg/
day
for
inhalation].

As
shown
on
Table
17,
many
of
these
MOEs
are
not
of
concern
with
the
addition
of
gloves
(
PPE).
The
total
dermal
and
inhalation
MOEs
with
PPE
(
gloves)
are
not
of
concern
for
the
majority
of
scenarios
evaluated.
The
total
MOEs
are
of
concern
(
i.
e.,
less
than
100)
for
the
following
exposure
scenarios:

 
Paint
Application
 
Airless
Sprayer:
MOE
=
16
 
Paint
Application
 
Paintbrush:
MOE
=
95
Postapplication
Exposure
and
Risk.

Metal
Working
Fluid
Use.
There
is
a
potential
for
dermal
and
inhalation
exposure
when
a
worker
handles
treated
metal
working/
cutting
fluids.
Exposure
can
occur
after
the
chemical
has
been
incorporated
into
the
cutting
fluid
and
a
machinist
is
using/
handling
this
treated
end­
product.
The
Agency
evaluated
both
dermal
and
inhalation
exposures
for
short­,
intermediate­
and
long­
term
exposure
durations.
Dermal
exposure
estimates
were
derived
using
the
2­
hand
immersion
model
from
ChemSTEER.
A
screening­
level
intermediate
and
long
term
inhalation
exposure
estimate
for
treated
cutting
fluids
has
been
developed
using
the
OSHA
PEL
for
oil
mist.
Table
18
presents
a
summary
of
the
risk
estimates
for
occupational
exposure
to
TCMTB­
containing
metal
working/
cutting
fluids.

Wood
Preservative
Use.
TCMTB
is
used
in
products
that
are
intended
to
preserve
wood
through
primarily
non­
pressure­
treatment
methods.
It
can
be
applied
as
a
sapstain
control
to
freshly­
cut
wood,
incorporated
into
particle
board,
or
used
to
treat
wood
chips.
When
used
as
a
sapstain
control,
the
product
may
be
dipped,
sprayed,
or
impregnated
into
the
wood
via
pressure
treatment
(
up
to
0.3%
a.
i.
solution).
When
used
in
particle
board,
the
pesticide
is
incorporated
into
the
resin
or
binding
agent
(
0.3%
a.
i.,
based
on
dry
weight
of
wood).

For
the
occupational
postapplication
risk
assessment,
the
MOEs
were
above
target
MOE
of
100
for
short­
and
intermediate­
term
dermal
and
inhalation
exposures,
and
were
above
300
for
long­
term
durations,
and
therefore
not
of
concern
for
all
scenarios.
The
Page
49
of
66
occupational
risks
for
metal
working
fluid
exposures
and
wood
preservative
uses
are
presented
on
Tables
18
and
19,
respectively.

Table
18
Short­,
Intermediate­,
and
Long­
Term
Risks
Associated
with
Postapplication
Exposure
to
Metal
Working
Fluids
treated
with
TCMTB
(
Machinist)

Dermal
Inputs
Inhalation
Inputs
MOE
(
Target
MOE
 
100
for
ST/
IT,
300
for
LT)
c,
d
Dermal
MOE
Inhalation
MOE
TOTAL
MOE
(
dermal
and
inhalation)
Weight
Fraction
a.
i.
in
Fluid
Hand
Surface
Area
(
cm2)
Film
thickness
(
mg/
cm2)
Frequency
(
event/
day)
OSHA
PEL
(
mg/
m3)
Inhal.
rate
(
m3/
hr)
Exposure
Duration
(
hrs/
day)

ST/
IT/
LT
ST/
IT
LT
ST/
IT
LT
0.00125
840
1.75
1
5
1
8
950
22000
5300
910
806
a
Absorbed
Dermal
Daily
Dose
(
mg/
kg/
day)
=
[
fraction
a.
i.
in
treated
fluid
*
hand
surface
area*
film
thickness
(
mg/
cm2)*
Frequency
(
event/
day)]
/
Body
weight
(
70
kg).
b
Absorbed
Inhalation
Daily
Dose
(
mg/
kg/
day)
=
fraction
a.
i.
in
treated
fluid
*
OSHA
PEL
(
mg/
m3)
*
Inhalation
rate
(
m3/
hr)
*
exposure
duration
(
hr/
day)
/
body
weight
(
70
kg)
c
Dermal
MOE
=
NOAEL
(
mg/
kg/
day)
/
Absorbed
Daily
Dose
(
mg/
kg/
day)
[
Where:
ST/
IT/
LT
dermal
NOAEL
=
25
mg/
kg/
day].
d
Inhalation
MOE
=
NOAEL
(
mg/
kg/
day)
/
Absorbed
Daily
Dose
(
mg/
kg/
day)
[
Where:
ST/
IT
inhalation
NOAEL
=
16
mg/
kg/
day
and
LT
Inhalation
NOAEL
=
3.8
mg/
kg/
day].

Table
19.
Short­,
Intermediate­
and
Long­
Term
Exposures
and
Risks
for
Wood
Preservative
Use
MOEsc
(
Target
MOE
 
100
for
ST/
IT,
300
for
LT)

Dermal
Inhalation
TOTAL
MOE
(
dermal
and
inhalation)
Exposure
Scenarioa
(
number
of
volunteers)
ST/
IT/
LT
ST/
IT
LT
ST/
IT
LT
Blender/
Spray
Operator
(
b)
520
5,200
1,200
478
364
Chemical
Operator
(
n=
11)
48,000
1.10x107
2.50x106
47,790
47,095
Grader
(
n=
13)
1.50x105
1.00x107
2.40x106
147,783
141,176
Trim
Saw
(
n=
2)
3.40x105
4.90x106
1.20x106
317,940
264,935
Millwright
(
n=
3)
36,000
5.20x106
1.20x106
35,752
34,951
Clean­
Up
(
n=
6)
8,400
4.90x105
1.20x105
8,258
7,850
Diptank
Operator
1,900
8.10x104
19,000
1,856
1,727
ST
=
Short­
term
duration;
IT
=
Intermediate­
term
duration;
and
LT
=
long­
term
a.
Unless
specified,
the
exposure
scenario
represents
a
worker
wearing
short
sleeve
shirts,
cotton
work
trousers,
and
cotton
glove
dosimeter
gloves
under
chemical
resistant
gloves.
Volunteers
were
grouped
according
to
tasks
they
conducted
at
the
mill.
b.
Single
layer
clothing
with
chemical
resistant
c
MOE
=
NOAEL
(
mg/
kg/
day)/
Daily
dose
[
Where
ST/
IT/
LT
dermal
NOAEL
=
25
mg/
kg/
day,
ST/
IT
NOAEL
for
inhalation
is
16
mg/
kg/
day
and
LT
NOAEL
for
inhalation
is
3.8
mg/
kg/
day].
Target
MOE
is
100
for
ST/
IT
dermal
and
inhalation
exposures,
300
for
LT
dermal
and
inhalation
exposure.
Page
50
of
66
10.0
ENVIRONMENTAL
RISK
A
detailed
ecological
hazard
and
environmental
risk
assessment
for
TCMTB
is
presented
in
the
attached
memorandum
(
memo
from
K.
Montague/
S.
Gowda/
S.
Mostaghimi,
April
6,
2006).
A
brief
summary
is
presented
below.

10.1
Environmental
Modeling/
Exposure
TCMTB
shows
pH­
dependent
hydrolytic
degradation.
While
hydrolytically
stable
at
pH
5,
the
half­
life
at
pH
9
is
1.8­
2.1
days.
TCMTB
breaks
down
rapidly
by
photolysis,
with
a
half
life
of
1.5
hours.
Biotic
degradation
also
occurs,
with
half­
lives
ranging
from
1.4
days
in
soil
under
aerobic
conditions
to
6.9
days
in
water/
sediment
systems
under
anaerobic
conditions.
TCMTB
is
mobile­
very
mobile
in
various
soils,
which
indicates
that
runoff
into
aquatic
habitats
is
a
potential
concern.
The
Kow
of
TCMTB
is
1995.
A
Kow
>
1000
indicates
that
a
chemical
may
potentially
bioconcentrate;
however,
the
results
of
a
bioconcentration
study
in
fish
indicate
that
bioconcentration
of
TCMTB
will
be
minimal.

Several
major
metabolites
are
formed
during
the
biotic
degradation
processes
of
TCMTB,
including
2­
benzothiazolesulfonic
acid
(
BTSA)
and
2­
mercaptobenzothiazole
(
2­
MBT).
BTSA
is
not
of
toxicological
concern
due
to
being
completely
excreted
(
sulfonic
acid)
and
having
negligible
toxicity.
2­
MBT
is
generally
less
toxic
than
parent
TCMTB;
therefore,
mitigation
of
any
risks
from
TCMTB
toxicity
endpoints
will
be
protective
of
any
risks
from
2­
MBT.
Therefore,
the
environmental
risk
assessment
was
conducted
for
TCMTB
only.

10.2.
Ecological
Toxicity
Data.

The
acute
toxicity
data
for
TCMTB
are
summarized
on
Table
20.
As
shown
in
Tables
20
and
21,
TCMTB
is
slightly
toxic
and
2­
MBT
is
practically
non­
toxic
to
birds
on
an
acute
oral
basis,
and
both
TCMTB
and
2­
MBT
are
slightly
toxic
to
birds
on
a
subacute
dietary
basis.

Based
on
the
results
of
mammalian
studies
conducted
to
meet
human
toxicity
data
requirements,
TCMTB
exhibits
low
acute
oral
and
dermal
toxicity
(
toxicity
category
III).
However,
it
is
highly
irritating
to
the
eyes
and
skin
(
toxicity
category
I
and
II,
respectively)
and
is
also
considered
to
be
highly
toxic
via
the
inhalation
route
of
exposure
(
toxicity
category
I).
TCMTB
is
a
dermal
sensitizer.
The
NOAEL
determined
in
a
rat
2­
generation
reproduction
study
was
400
ppm.

Both
TCMTB
and
2­
MBT
are
very
highly
toxic
to
freshwater
fish,
and
estuarine/
marine
fish
on
an
acute
basis.
As
shown
on
Table
22,
chronic
testing
indicates
that
TCMTB
causes
reproduction
and
growth
effects
in
fish
at
very
low
levels
(>
0.34
ppb.
TCMTB
is
very
highly
toxic
and
2­
MBT
is
moderately
toxic
to
freshwater
aquatic
invertebrates
on
an
acute
basis,
and
TCMTB
also
shows
very
high
acute
toxicity
to
marine/
estuarine
invertebrate
species.
Page
51
of
66
A
chronic
freshwater
invertebrate
study
is
outstanding.
One
daphnid
life­
cycle
study
was
submitted
(
MRID#
425591­
01),
but
was
invalidated
due
to
high
variablility
in
the
test
concentrations
to
which
the
daphnids
were
exposed.
A
new
daphnid
life­
cycle
study
(
72­
4b/
850.1400)
is
required
to
support
the
currently
registered
uses
of
TCMTB.

Some
reports
in
the
published
literature
indicate
that
TCMTB
may
cause
sublethal
effects
in
fish,
which
could
result
in
an
increase
in
predation
and
a
decreased
ability
to
survive.
This
information
was
submitted
to
the
Agency
under
FIFRA
§
6(
a)
2
(
MRID
#
424053­
01).
These
studies
demonstrate
that
exposure
to
TCMTB
at
levels
of
8­
10
ppb
caused
gill
damage
and
behavioral
changes,
which
could
severely
reduce
the
ability
of
fish
to
survive
in
the
wild.
From
Proceedings
of
the
Seventeenth
Annual
Aquatic
Toxicity
Workshop,
Nov.
5­
7,
1990,
Vancouver,
BC,
Vol.
1.
(
edited
by
P.
Chapman,
F.
Bishay,
E.
Power,
K.
Hall,
L.
Harding,
D.
Mcleay,
M.
Nassichuk
and
W.
Knapp).
Canadian
Technical
report
of
Fisheries
and
Aquatic
Sciences,
No.
1774
(
vol
1).
Individual
paper
citations:
(
Kruzynski
and
Birtwell,
1990;
Kruzynski
et
al.,
1990;
Chew
et
al.,
1990).
The
LC50
used
in
this
risk
assessment
(
8.7
µ
g/
L)
is
comparable
to
the
levels
at
which
these
sublethal
effects
occurred,
however,
so
the
risk
assessment
should
be
protective
of
those
effects.

Table
20.
Acute
Toxicity
of
TCMTB
and
2­
MBT
Species
Chemical
%
active
ingredient
(
ai)
Endpoint
Toxicity
Category
(
TGAI)
Other
Effects
Noted
Reference/
Status
Birds
TCMTB
80.4%
LD50
=
660
mg/
kg
NOEL
<
292
mg/
kg
Slightly
toxic
Signs
of
toxicity
and
reduction
of
body
weight
and
feed
consumption
at
292
mg/
kg
MRID:
41780901
(
Campbell
1991)/
Acceptable
Northern
bobwhite
(
Colinus
virginianus)

2­
MBT
98.2%
LD50
>
2150
mg/
kg
NOEL
<
1000
mg/
kg
Practically
non­
toxic
Some
evidence
of
dose­
related
abnormalities
upon
gross
necropsy
(
friable
livers,
resorbed
eggs,
fluid­
filled
sacs
in
abdomen)
MRID:

42267101
(
Pedersen
end
Helsten
1992a)/

Acceptable
Mammals
Laboratory
rat
(
Rattus
norvegicus)
TCMTB
80%
ai
LD50=
750
mg/
kg
Moderately
toxic
41583801/
Acceptable
Freshwater
Fish
Rainbow
trout
Oncorhynchu
s
mykiss)
TCMTB
90%
96hr
static
LC50
=

55.2
ug/
L
(
ppb)
Very
highly
toxic
None
reported
TN
2437
(
USEPA
1980)/
Supplemental
Page
52
of
66
Table
20.
Acute
Toxicity
of
TCMTB
and
2­
MBT
Species
Chemical
%
active
ingredient
(
ai)
Endpoint
Toxicity
Category
(
TGAI)
Other
Effects
Noted
Reference/
Status
TCMTB
80.4%
96hr
flow
through
LC50
=
20.91
ug/
L
(
ppb)
Very
highly
toxic
NOEC
=
8.7
µ
g/
L
(
ppb)
due
to
mortality
and
lethargy
and
loss
of
equilibrium
in
surviving
fish
at
higher
levels
41818101
(
Machado
1991b)/
Acceptable
TCMTB
75%
96hr
static
LC50
=

29
ug/
L
(
ppb)
Very
highly
toxic
Loss
of
equilibrium
and
lying
on
sides
observed
ACC+
0916
24
(
Knott
and
Woodard
1968b)/
Supplemental
TCMTB
90%
96hr
static
LC50
=

32
ug/
L
(
ppb)
Very
highly
toxic
None
reported
TN
2432
(
USEPA
1979)/
Supplemental
TCMTB
80.4%
96hr
flow
through
LC50
=
8.7
ug/
L
(
ppb)
Very
highly
toxic
NOEC
=
5.1
µ
g/
L
(
ppb)
due
to
signs
of
toxicity
at
higher
levels
41804201
(
Machado
1991a)/
Acceptable
Bluegill
sunfish
(
Lepomis
macrochirus)

TCMTB
75%
96hr
static
LC50
=

47
ug/
L
(
ppb)
Very
highly
toxic
Loss
of
equilibrium
and
lying
on
sides
observed
ACC#
091624
(
Knott
and
Woodard
1968b)/

Supplemental
Rainbow
trout
Oncorhynchu
s
mykiss)
2­
MBT
98.2%
96
hr
static
LC50
=
730
ug/
L
(
ppb)
Very
highly
toxic
NOEC
=
310
µ
g/
L
(
ppb)
due
to
mortality
at
higher
treatment
levels
42232201
(
Collins
1992)/
Acceptable
Freshwater
Invertebrates
TCMTB
90%.
48­
hr.
static
EC50
=
23
ug/
L
(
ppb)
Very
highly
toxic
TN
2427
(
USEPA
1979)/

Supplemental
TCMTB
80.4%
48­
hr.
flow
through
EC50
=
22
ug/
L
(
ppb);
NOEC
=
8.7
ug/
L
(
ppb)
Very
highly
toxic
41838201
(
McNamara
1991)/
Acceptable
Waterflea
(
Daphnia
magna)

2­
MBT
100%
48­
hr.
static
EC50
=
2,900
ug/
L
(
ppb)
Moderately
toxic
42226001
(
Collins
1992b)/
Acceptable
Estuarine/
Marine
Fish
Sheepshead
minnow
(
Cyprinodon
TCMTB
80%
96
hr.
static
LC50
=
60
ug/
L
(
ppb)
Very
highly
toxic
40363601
(
Suprenant
1986a)/
Acceptable
Page
53
of
66
Table
20.
Acute
Toxicity
of
TCMTB
and
2­
MBT
Species
Chemical
%
active
ingredient
(
ai)
Endpoint
Toxicity
Category
(
TGAI)
Other
Effects
Noted
Reference/
Status
variegates)
Estuarine/
Marine
Invertebrates
Quahog
clam
(
Mercenaria
mercenaria)
TCMTB
80%
48­
hr.
static
EC50
=
13.9
ug/
L
(
ppb);
NOEC
<
13
ug/
L
(
ppb)
Very
highly
toxic
.
40363603
(
Suprenant
1986)
/
Acceptable
Mysid
(
Americamys
is
bahia,
formerly
Mysidopsis
bahia)
TCMTB
80%
96­
hour
static
LC50=
20.3
ug/
L
(
ppb);
NOEC
<
7.8
ug/
L
(
ppb)
Very
highly
toxic
40363602
(
Suprenant
1987)
/
Acceptable
Table
21.
Avian
Subacute
Dietary
Toxicity
of
TCMTB
and
2­
MBT
Test
Type
(
Chemica
l
and
%
a.
i.)
Chemical
(%
a.
i.)
Species
Endpoint
Results
Other
Effects
Noted
Reference/
Status
TCMTB
(
80­
83%
a.
i.)
Mallard
duck
(
Anas
platyrhyncho
s)
Mortality
8­
day
LC50
>
10000
ppm
"
practically
non­
toxic"
Feed
consumption
and
10%
mortality
at
5,000
and
10,000
ppm
Accession
#
009869
(
Booden,
1974)/
Acceptable
TCMTB
(
75
%
a.
i.)
Bobwhite
quail
(
Colinus
virginianus)
Mortality
LC50
>
10000
ppm
"
Practically
non­
toxic"
Huddling
and
depression
at
levels
>
1000
ppm
Accession
#
091624
(
Knott
and
Woodard,
1968a)/
Supplement
al
TCMTB
(
80%
a.
i.)
Mallard
duck
(
Anas
platyrhyncho
s)
Mortality
8­
day
LC50
>
4496
ppm
"
Slightly
toxic"
NOEC
<
450
ppm
based
on
reduction
in
body
weight
gain
and
food
consumption
415956­
01
(
Long
et
al.,
1990/
Acceptable
TCMTB
(
80%
a.
i.)
Bobwhite
quail
(
Colinus
virginianus)
Mortality
8­
day
LC50
>
4496
ppm
"
Slightly
toxic"
NOEC
=
450
ppm,
based
on
reduction
of
average
body
weight
gain
at
higher
levels
415956­
02
(
Long
et
al.,
1990/
Acceptable
Avian
acute
dietary,
850.2200/
71­
2
2­
MBT
(
98.22%
a.
i.)
Bobwhite
quail
(
Colinus
virginianus
Mortality
8­
day
LC50
>
3387
ppm
"
Slightly
toxic"
NOEC
=
3387
ppm
 
no
signs
of
toxicity
at
any
level
424285­
01(
Pederse
n
and
Helsten,
1992b)/
Acceptable
Page
54
of
66
Table
22:
Chronic
Toxicity
Values
for
Freshwater
Fish
Exposed
to
TCMTB
Study
Type
Species
Endpoint
NOEC

g
a.
i./
l
LOEC

g
a.
i./
l
MRID#
(
reference)/
Status
Freshwater
fish
Early
life­
stage
toxicity
(
72­
4a/
850.1300)
(
83.78%
a.
i.)
Rainbow
trout
(
Oncorhynch
us
mykiss)
Reproduction,
post­
hatch
survival,
growth
0.34
ppb
based
on
growth
and
egg
hatchability
0.56
ppb
based
on
growth
425959­
01
(
Rhodes,
1992)/
Acceptable
No
terrestrial
or
semi­
aquatic
plant
toxicity
data
have
been
submitted
for
TCMTB.
These
data
are
required
to
support
the
currently
registered
uses
of
TCMTB.
Guidelines
123­
1/
850.4225
and
850.4250
(
Tier
II
seedling
emergence
and
vegetative
vigor)
for
rice
are
required
to
support
wood
preservative
uses.
Guideline
122­
1/
850.4100
(
Tier
I
seedling
emergence)
for
10
species
of
terrestrial
plants
(
to
support
seed
treatment
uses)
is
also
required.
Guideline
123­
1/
850.4100
(
Tier
II
seedling
emergence)
is
reserved
for
seed
treatment
uses,
pending
the
results
of
the
Tier
I
test.

As
shown
on
Table
23,
a
single
aquatic
plant
study
was
submitted
for
TCMTB,
which
shows
that
TCMTB
impairs
growth
of
aquatic
vascular
plants
at
levels
greater
than
0.15
ppm
(
150
ppb).
Additional
aquatic
phytotoxicity
testing
with
four
species
of
algae
is
required
to
support
the
currently
registered
uses
of
TCMTB.

Table
23:
Toxicity
of
TCMTB
to
Aquatic
Plants
Test
Species/%
a.
i.
Endpoint
Toxicity
NOEC/
othe
r
effects
noted
MRID
(
reference)
Status
Aquatic
Vascular
Plant
Acute
Toxicity,
Tier
II
(
dose­
response),
123­
2/
850.4400
Duckweed
(
Lemna
gibba)/
83.5%
a.
i.
Frond
growth
14­
day
static
renewal
EC50
=
0.43
(
0.29
 
0.65)
mg/
L
(
ppm)
0.15
mg/
L
(
ppm)
442009­
01
(
Thompson
and
Swigert,
1996)
Acceptable
10.3
Bioaccumulation
in
Aquatic
Organisms.

The
log
octanol­
water
coefficient
(
log
Kow)
of
TCMTB
is
3.23.
Bioconcentration
testing
is
required
for
chemicals
having
a
log
Kow
>
3.00
if
they
are
likely
to
result
in
exposure
to
aquatic
organisms,
so
this
testing
was
required
for
TCMTB.

Radiolabeled
residues
accumulated
in
bluegill
sunfish
that
were
exposed
to
uniformly
phenyl­
ring
labeled
[
14C]
TCMTB,
at
a
nominal
concentration
of
0.40

g/
L,
Page
55
of
66
under
flow­
through
aquarium
conditions
(
MRID
#
424185­
01,
424932­
01,
and
467052­
01).
Maximum
bioconcentration
factors
(
BCF),
based
on
total
radioactivity
were
302X
for
viscera,
64X
for
fillet,
and
184X
for
whole
fish
tissues.
Seventy­
five
to
77%,
84­
87%,
and
84­
86%
of
the
mean
accumulated
[
14C]
residues
(
exposure
days
14­
28)
were
eliminated
from
the
fillet,
viscera
and
whole
fish
tissues,
respectively,
by
days
21­
35.
These
results
indicate
that
the
bioaccumulation
potential
of
TCMTB
is
minimal.

10.4
Environmental
Exposure
Assessment
Aquatic
exposure
from
seed
treatment
uses
of
TCMTB
was
modeled
by
the
Environmental
Fate
and
Effects
Division
(
EFED),
where
the
Agency
estimated
environmental
concentrations
(
EEC)
for
the
use
of
TCMTB
as
a
seed
treatment
on
cotton,
wheat,
barley,
oats,
rice,
sugar
beets,
and
safflower.
For
this
action,
EFED
considered
risk
only
from
parent
compound
of
TCMTB
and
not
any
degradates
associated
with
TCMTB.
For
this
screening­
level
aquatic
exposure
assessment,
the
highest
rate
of
0.041
lb
ai/
ac
is
used,
along
with
the
tier
1
GENEEC
and
SCI­
GROW
models
to
assess
estimated
concentrations
of
TCMTB
in
surface
water
and
ground
water,
respectively.

For
surface
water
exposures,
results
from
GENEEC
indicate
that
the
TCMTB
concentrations
of
0.28
ppb
(
ug/
L),
0.26
ppb,
0.20
ppb,
0.12
ppb,
and
0.08
ppb,
respectively,
for
peak,
4­
day
average,
21­
day
average,
60­
day
average,
and
90­
day
average
exposure.
For
ground
water,
SCI­
GROW
indicates
that
TCMTB
concentrations
are
not
likely
to
exceed
0.00014
ug/
L.

In
addition,
the
Agency
conducted
environmental
exposure
modeling
for
the
antisapstain
wood
preservation
use.
Runoff
concentrations
of
TCMTB
were
estimated
for
facilities
that
treat
wood
with
antisapstain
chemicals.
The
concentrations
were
estimated
using
an
approach
developed
to
determine
runoff
concentrations
of
pesticides
from
antisapstain
facilities
in
British
Columbia,
Canada
(
Krahn
and
Strub,
1990).

Krahn
and
Strub
(
1990),
in
their
protocol
for
a
leaching
study,
suggest
that
treated
wood
be
stored
outdoors,
stacked
into
lumber
packages
24"
x
48"
x
16',
and
placed
over
leachate
collection
trays
(
1.52
m
x
5.2
m).
A
total
of
16
leaching
cycles
should
be
applied
at
a
rate
of
15
mm/
day
every
other
day,
with
each
rain
duration
lasting
5
hours
and
a
target
intensity
of
3
mm/
hr.
These
values
are
based
on
the
average
precipitation
that
occurs
in
British
Columbia
in
the
worst­
case
month
of
the
year.

Predictions
of
leaching
behavior
(
as
would
be
observed
in
a
study
following
the
Krahn
and
Strub
(
1990)
protocol)
were
made
based
on
the
chemical
properties
of
TCMTB
and
a
number
of
assumptions
(
see
Antisapstain
Environmental
Modeling
Chapter
for
details).

Aschacher
and
Gruendlinger
(
2000)
have
measured
uptake
of
antisapstain
dipping
solution
by
pine
boards.
Freshly
sawn
pine
boards
(
2.3
x
10
x
50
cm,
code
R2
and
R2
Ab)
were
dipped
into
a
1.5%
Busan
30
L
solution
(
a.
i.:
2­
thiocyanomethylthio­
benzthiazole,
TCMTB).
One
set
of
samples
was
treated
in
April
1997,
and
another
set
was
treated
in
Page
56
of
66
April
1998.
For
each
type
of
board
treated
each
year,
the
uptake
was
measured
based
on
the
average
of
7
boards.
The
average
uptake,
based
on
the
measurement
of
28
boards,
was
163
g
solution/
m2.

Krahn
and
Strub
(
1990)
assume
that
leachate
entering
the
storm
drain
is
diluted
with
extra
runoff
water
at
a
1:
15
ratio.
This
is
based
on
measurements
of
runoff
in
storm
drains
at
facilities
using
antisapstain
chemicals
in
British
Columbia.
Use
of
the
ratios
1:
6
and
1:
23
were
also
suggested
by
Krahn
and
Strub
(
1990)
to
determine
a
"
general
industry
wide"
predicted
runoff
concentration.
These
values
were
used
in
this
assessment.
The
estimated
leachate
concentration
(
0.196
ppm)
was
used
in
conjunction
with
these
dilution
factors
to
estimate
runoff
concentrations
Table
24.
Estimated
Runoff
Concentrations
for
TCMTB
from
Antisapstain
Use
Parameter
Dilution
Factor
Estimated
Runoff
Concentration
(
ppm)
a
High­
end
dilution
23.0
0.00852
Typical
dilution
15.0
0.0131
Low­
end
dilution
6.00
0.0327
aEstimated
Runoff
Concentration
=
Estimated
Leachate
Concentration
(
0.196
ppm)
/
Dilution
Factor
10.5
Ecological
Risk
Characterization
Risk
assessment
integrates
the
results
of
the
exposure
and
ecotoxicity
data
to
evaluate
the
likelihood
of
adverse
ecological
effects.
One
method
of
integrating
the
results
of
exposure
and
ecotoxicity
data
is
called
the
quotient
method.
For
this
method,
risk
quotients
(
RQs)
are
calculated
by
dividing
exposure
estimates
by
ecotoxicity
values,
both
acute
and
chronic:

RQ
=
EXPOSURE/
TOXICITY
RQs
are
then
compared
to
levels
of
concern
(
LOCs).
These
LOCs
are
criteria
used
by
OPP
to
indicate
potential
risk
to
nontarget
organisms
and
the
need
to
consider
regulatory
action.
The
criteria
indicate
that
a
pesticide
used
as
directed
has
the
potential
to
cause
adverse
effects
on
nontarget
organisms.
LOCs
currently
address
the
following
risk
presumption
categories:
(
1)
acute
high
­
potential
for
acute
risk
is
high
regulatory
action
may
be
warranted
in
addition
to
restricted
use
classification;
(
2)
acute
restricted
use
­
the
potential
for
acute
risk
is
high,
but
this
may
be
mitigated
through
restricted
use
classification;
(
3)
acute
endangered
species
­
the
potential
for
acute
risk
to
endangered
species
is
high,
and
regulatory
action
may
be
warranted,
and
(
4)
chronic
risk
­
the
potential
for
chronic
risk
is
high,
and
regulatory
action
may
be
warranted.
Currently,
AD
does
not
perform
assessments
for
chronic
risk
to
plants,
acute
or
chronic
risks
to
nontarget
insects,
or
chronic
risk
from
granular/
bait
formulations
to
mammalian
or
avian
species.

Terrestrial
Organisms.
Modeling
was
performed
to
address
the
exposure
and
risk
to
birds
and
mammals
consuming
seeds
treated
with
TCMTB.
Using
the
Terrestrial
Residue
Exposure
Model
(
TREX)
(
http://
www.
epa.
gov/
oppefed1/
models/
terrestrial/)
for
the
seed
treatment
on
safflower,
which
has
the
highest
application
rate
of
0.041
lb
ai/
A,
the
following
RQs
for
seed
treatment
were
calculated:
Page
57
of
66
Avian:
:
0.02
as
(
mg
ai/
kg/
day)/
LD50
The
avian
RQ
was
calculated
with
no
toxicity
scaling
factor.
Scaling
factors
are
used
when
it
is
likely
that
a
pesticide
will
be
proportionally
more
toxic
to
smaller
organisms
than
larger
ones
(
e.
g.,
the
toxicity
will
not
be
directly
correlated
with
body
weight).
TREX
recommends
a
default
scaling
factor
of
1.15,
based
on
Mineau
et
al.
(
1996);
however,
that
scaling
factor
was
developed
based
on
37
conventional
pesticides,
most
of
which
are
cholinesterase
inhibitors.
There
is
no
information
available
indicating
that
such
an
adjustment
is
necessary
or
appropriate
for
TCMTB.

Mammalian
Acute:
0.05
as
(
mg
ai/
kg/
day)/
LD50,
0.02
as
(
mg
ai/
ft2)/(
LD50*
BW)
Chronic:
0.53
as
(
mg/
kg
seed)/
reproduction
NOAEC
All
of
these
are
below
any
LOCs
for
avian
or
mammalian
acute
risk
and
mammalian
chronic
risk.
Avian
chronic
data
are
not
available
nor
required
for
the
currently
registered
uses
of
TCMTB,
therefore
chronic
avian
risk
was
not
assessed.

Aquatic
Organisms:
To
develop
RQs,
the
EECs
determined
by
modeling
were
compared
to
the
most­
sensitive
endpoint
for
each
taxa.
For
seed
treatment,
the
peak
EEC
was
used
for
acute
and
endangered
species
risks,
the
21­
day
average
was
used
for
invertebrate
chronic
risk,
and
the
60
day
average
was
used
for
the
fish
chronic
risk.
For
antisapstain
uses,
the
worst­
case
scenario
(
low
dilution)
and
the
"
best­
case"
(
high
dilution)
EECs
were
used
for
acute
and
endangered
species
risks,
and
the
typical
dilution
was
used
for
fish
and
invertebrate
chronic
risks.
RQs
exceeding
one
or
more
LOCs
(
listed
in
the
risk
presumptions
section,
above)
are
in
bold
text.

Table
25:
Aquatic
Organism
Risk
Quotients
for
Seed
Treatment
and
Antisapstain
Uses
of
TCMTB
Taxa/
Endpoint
Seed
treatment
EEC
(
peak)
Seed
Treatment
RQ
Antisapstain
EEC
Low
dilution
High
dilution
Antisapstain
RQ
Freshwater
fish
Acute
8.7
ppb
0.28
ppb
0.03
32.7
ppb
8.5
ppb
3.76
0.98
Freshwater
Invertebrates
Acute
22
ppb
0.28
ppb
0.01
32.7
ppb
8.5
ppb
1.49
0.39
Marine/
Estuarine
Fish
Acute
60
ppb
0.28
ppb
0.00
32.7
ppb
8.5
ppb
0.54
0.14
Marine/
Estuarine
Bivalve
Acute
13.9
ppb
0.28
ppb
0.02
32.7
ppb
8.5
ppb
2.35
0.61
Marine/
Estuarine
Invertebrate
Acute
20.3
ppb
0.28
ppb
0.01
32.7
ppb
8.5
ppb
1.61
0.42
Green
Algae
Acute
EC50
430
ppb
0.28
ppb
0.00
32.7
ppb
8.5
ppb
0.08
0.02
Green
Algae
NOEC
150
ppb
0.28
ppb
0.00
32.7
ppb
8.5
ppb
0.22
0.06
Fish
Chronic
0.34
ppb
0.12
ppb
0.35
13.1
ppb
8.5
ppb
38.53
25.00
Page
58
of
66
Invertebrate
Chronic
 
DATA
GAP
0.20
ppb
­­­­­
13.1
ppb
­­­­­

For
seed
treatment,
no
LOCs
are
exceeded,
indicating
that
the
use
poses
minimal
risk
to
aquatic
organisms.

For
the
antisapstain
use,
the
low
dilution
(
worst­
case)
EECs
exceed
acute
high
risk
LOCs
for
all
taxa,
and
chronic
risk
to
fish.
Even
using
the
high
dilution
("
best­
case")
EECs
still
results
in
exceedance
of
acute
high
risk
LOCs
for
freshwater
fish
and
marine
bivalves,
and
restricted
use
LOCs
for
freshwater
invertebrates,
marine
fish
and
marine
invertebrates,
and
chronic
risk
to
fish.

Chronic
risk
to
invertebrates
cannot
be
assessed
at
this
time
due
to
the
lack
of
chronic
invertebrate
toxicity
data.

The
model
used
to
estimate
exposure
from
antisapstain
uses
is
intended
as
a
Tier
I
screening
model,
and,
as
such,
has
inherent
assumptions
and
uncertainties
that
may
result
in
overor
under­
estimation
of
exposure
levels.
Additional
information,
including,
but
not
limited
to,
specific
leaching
data
for
TCMTB
used
as
an
antisapstain
wood
preservative,
would
remove
some
of
the
uncertainties,
and
may
result
in
more
accurate
exposure
estimation.
An
environmental
monitoring
study
is
also
needed
to
address
the
potential
risks
of
concern
and
provide
EECs
for
a
refined
risk
assessment.

Methods
to
reduce
the
amount
of
TCMTB
potentially
released
from
antisapstain­
treated
wood
would
mitigate
the
risks.
Possible
mitigation
methods
might
include
lowering
the
application
rate
or
requiring
specific
storage
conditions
to
prevent
exposure
of
recently
treated
wood
to
weather
(
e.
g.,
full
covering)
and/
or
prevent
the
release
of
any
associated
runoff
into
aquatic
habitats
(
e.
g.,
drip
pads).
TCMTB
is
very
mobile
in
soils,
so
any
TCMTB
leached
outdoors
will
likely
reach
aquatic
habitats.

10.6
Endangered
Species
Considerations
Section
7
of
the
Endangered
Species
Act,
16
U.
S.
C.
Section
1536(
a)(
2),
requires
all
federal
agencies
to
consult
with
the
National
Marine
Fisheries
Service
(
NMFS)
for
marine
and
anadromous
listed
species,
or
the
United
States
Fish
and
Wildlife
Services
(
FWS)
for
listed
wildlife
and
freshwater
organisms,
if
they
are
proposing
an
"
action"
that
may
affect
listed
species
or
their
designated
habitat.
Each
federal
agency
is
required
under
the
Act
to
insure
that
any
action
they
authorize,
fund,
or
carry
out
is
not
likely
to
jeopardize
the
continued
existence
of
a
listed
species
or
result
in
the
destruction
or
adverse
modification
of
designated
critical
habitat.
To
jeopardize
the
continued
existence
of
a
listed
species
means
"
to
engage
in
an
action
that
reasonably
would
be
expected,
directly
or
indirectly,
to
reduce
appreciably
the
likelihood
of
both
the
survival
and
recovery
of
a
listed
species
in
the
wild
by
reducing
the
reproduction,
numbers,
or
distribution
of
the
species."
50
C.
F.
R.
'
402.02.

To
facilitate
compliance
with
the
requirements
of
the
Endangered
Species
Act
subsection
(
a)(
2)
the
Environmental
Protection
Agency,
Office
of
Pesticide
Programs
has
established
procedures
to
evaluate
whether
a
proposed
registration
action
may
directly
or
indirectly
reduce
Page
59
of
66
appreciably
the
likelihood
of
both
the
survival
and
recovery
of
a
listed
species
in
the
wild
by
reducing
the
reproduction,
numbers,
or
distribution
of
any
listed
species
(
U.
S.
EPA
2004).
After
the
Agency's
screening­
level
risk
assessment
is
performed,
if
any
of
the
Agency's
Listed
Species
LOC
Criteria
are
exceeded
for
either
direct
or
indirect
effects,
a
determination
is
made
to
identify
if
any
listed
or
candidate
species
may
co­
occur
in
the
area
of
the
proposed
pesticide
use.
If
determined
that
listed
or
candidate
species
may
be
present
in
the
proposed
use
areas,
further
biological
assessment
is
undertaken.
The
extent
to
which
listed
species
may
be
at
risk
then
determines
the
need
for
the
development
of
a
more
comprehensive
consultation
package
as
required
by
the
Endangered
Species
Act.

Using
Tier
I
screening
modeling
to
assess
potential
exposure
from
antisapstain
wood
preservation
uses
of
TCMTB,
risks
to
Listed
Species
are
indicated.
Since
the
model
is
only
intended
as
a
screening­
level
model,
and,
as
such,
has
inherent
uncertainties
and
limitations
which
may
result
in
inaccurate
exposure
estimations,
further
refinement
of
the
model
is
recommended
before
any
regulatory
action
is
taken
regarding
the
antisapstain
uses
of
TCMTB.
An
environmental
monitoring
study
of
runoff
from
antisapstain
treatment
facilities
is
needed
to
address
the
potential
risks
and
to
provide
EECs
for
use
in
a
refined
risk
assessment.
Additionally,
impacts
from
the
antisapstain
use
could
potentially
be
mitigated
with
precautions
to
prevent
leaching
and
runoff
when
wood
is
stored
outdoors.
Due
to
these
circumstances,
the
Agency
considers
the
antisapstain
use
NLAA,
provided
precautions
are
taken
to
prevent
the
leaching
and
runoff
of
TCMTB
into
aquatic
areas
(
see
Label
Hazard
Statements
and
Use
Recommendations
section,
below).
When
additional
data
are
available,
the
environmental
exposure
assessment
of
the
antisapstain
use
of
TCMTB
will
be
revised,
and
the
risks
to
Listed
Species
will
be
reconsidered.

11.0
DEFICIENCIES/
DATA
NEEDS
Hazard
Data
Gaps.
A
subchronic
inhalation
toxicity
study
is
triggered
because
many
of
the
inhalation
risks
exceed
the
Agency's
level
of
concern,
or
are
below
a
MOE
of
1000.
When
the
inhalation
endpoints
are
based
on
oral
toxicity
data,
it
is
current
Agency
policy
for
antimicrobial
chemicals
to
require
an
inhalation
toxicity
study
if
the
estimated
inhalation
MOEs
are
below
a
MOE
of
1000.
Also,
the
acute
toxicity
data
suggest
that
TCMTB
is
more
toxic
via
the
inhalation
route
of
exposure
(
Toxicity
category
I)
relative
to
oral
exposure
(
Toxicity
category
III),
and
thus
that
the
oral
toxicity
data
may
underestimate
the
actual
inhalation
risks
for
TCMTB.

Dietary
Data
Gaps
for
Antimicrobial
Use.

(
1)
The
registrant
must
address
the
question
of
whether
the
use
of
TCMTB
in
pulp
and
papermaking
will
result
in
residues
of
2­
mercaptobenzothiazole
(
2­
MBT)
in
paper
produced
using
TCMTB
and
provide
information
on
the
level
of
2­
MBT
that
will
occur
in
paper.
2­
MBT
is
the
main
mammalian
metabolite
of
TCMTB.
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).

(
2)
The
registrant
must
clarify
the
labeling
to
show
the
label
rates(
ranges)
for
the
paper
coating
Page
60
of
66
uses.
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.

(
3)
In
recent
correspondence
with
the
registrant
(
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?"
The
Agency
does
not
consider
label
restrictions
such
as,
"
Not
for
food
contact
use",
to
be
practical.
The
Agency
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
the
Agency
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.

Residue
Chemistry
Deficiencies
and
Regulatory
Guidelines
for
Agricultural
Uses
(
1)
Confirmatory
metabolism
data
should
be
submitted
depicting
the
nature
of
residues
in
wheat,
cotton,
and
sugar
beets;
(
2)
The
available
enforcement
method
(
Method
B
in
PAM
Vol.
II.)
is
outdated
and
uses
toxic
reagents;
therefore,
if
an
additional
method
that
is
adequate
for
tolerance
enforcement
is
available,
it
should
be
submitted
immediately
for
review;
(
3)
Storage
stability
data
were
not
included
with
the
original
field
trial
data
submissions;
therefore,
storage
stability
data
for
the
previously
submitted
field
trials
are
required
and
should
be
submitted
immediately;
(
4)
Storage
stability
and
method
data
were
not
provided
with
the
original
soil
persistence
studies
summarized
under
OPPTS
860.1850
in
this
document.
Storage
stability
and
method
data
are
required
and
should
be
submitted
immediately;
(
5)
Application
rates
in
lbs
a.
i./
100
lbs
seed
for
all
the
submitted
field
trial
studies
should
be
provided;
(
6)
Tolerances
for
barley
hay
and
cotton
gin
byproducts
should
be
proposed
once
the
requested
metabolism
data
are
submitted
and
reviewed;
(
7)
Data
should
be
submitted
which
show
whether
residues
concentrate
in
the
byproducts
of
the
registered
raw
agricultural
commodities;
(
8)
Magnitude
of
residue
data
in
sugar
beets
following
all
OPPTS
860
Series
Guidelines
should
be
submitted;
(
9)
Additionally,
numerous
OPPTS
860
Series
Guidelines
have
been
placed
on
reserve
pending
the
requested
plant
metabolism
data.

Residential/
Occupational
Data
Gaps.
Confirmatory
worker
exposure
data
are
necessary,
due
to
the
significant
limitations
of
the
existing
exposure
data
used
in
this
assessment.
The
Agency
is
requesting
worker
exposure
studies
that
evaluate
both
dermal
(
Guideline
875.1200)
and
inhalation
(
Guideline
875.1400)
exposure
for
indoor
uses.
The
Agency
also
requires
confirmation
of
descriptions
of
human
activity
(
875.2800)
associated
with
the
uses
assessed
in
this
document.
Page
61
of
66
In
addition,
the
Agency
requests
confirmatory
data
to
support
the
assumption
that
only
5%
of
TCMTB
is
transferred
from
treated­
textiles/
leather
to
skin.

Environmental
Fate
Data
Gaps:
The
following
data
requirements
are
outstanding
for
the
currently
registered
wood
preservation
and
seed
treatment
uses
of
TCMTB:
Hydrolysis
(
161­
1),
Aerobic
soil
metabolism
(
162­
1),
Anaerobic
soil
metabolism
(
162­
2),
Aerobic
aquatic
metabolism
(
162­
4),
and
Soil
column
leaching
study
(
163­
1).

The
following
data
requirements
are
reserved
for
TCMTB,
pending
the
results
of
lower
tier
testing
and
exposure
modeling:
Terrestrial
field
dissipation
(
164­
1)
(
seed
treatment
and
wood
preservation),
and
Aquatic
field
dissipation
(
164­
2)
(
wood
preservation)

Two
hydrolysis
studies
(
OPP
guideline
161­
1)
were
reviewed
by
the
Agency
and
found
scientifically
valid.
However,
information
on
instrumental
conditions,
mass
spectrum,
pH
and
temperature,
and
limits
of
detection
was
missing.
The
hydrolysis
data
requirement
for
TCMTB
has
been
partially
fulfilled.
Additional
data
are
necessary.

This
aerobic
aquatic
metabolism
study
(
Guideline
No.
OPP
162­
4)
was
reviewed
by
the
Agency
and
found
scientifically
valid.
However,
the
study
does
not
meet
guidelines
for
the
fulfillment
of
data
requirements
for
TCMTB
on
aerobic
aquatic
metabolism.
A
degradate
present
at
$
10%
of
the
applied
radioactivity
was
not
identified,
and
characterization
of
the
sediment
and
water
was
inadequate.
Additional
data
are
necessary.

This
aerobic
soil
metabolism
study
(
MRID
No.
435322­
01,
Guideline
No.
OPP
162­
1)
was
reviewed
by
the
Agency
and
found
scientifically
valid.
However,
the
study
does
not
meet
guidelines
for
the
fulfillment
of
data
requirements
for
TCMTB
on
aerobic
soil
metabolism.
The
study
was
not
conducted
for
a
sufficient
length
of
time
to
establish
the
patterns
for
the
formation
and/
or
decline
of
major
degradates.
Additional
data
are
necessary.

This
aqueous
availability
study
(
Guideline
No.
European
Standard
EN
84,
MRID
No.
441198­
02)
was
reviewed
by
the
Agency
and
found
useful
in
providing
supplemental
leaching
information
for
the
environmental
fate
assessment
of
TCMTB.
However,
this
study
was
not
performed
according
to
the
American
Wood
Preservers
=

Association
Standard:
"
Standard
Method
of
Determining
Leachability
of
Wood
Preservatives"
(
1998;
E11­
97;
324­
326).
This
study
should
be
repeated
following
these
guidelines.

Ecological
Data
Gaps.
The
following
data
requirements
are
outstanding
for
the
currently
registered
wood
preservation
and/
or
seed
treatment
uses
of
TCMTB:
Aquatic
invertebrate
life­
cycle
study
(
72­
4b/
850.1400),
Tier
II
seedling
emergence
and
vegetative
vigor
with
rice
(
123­
1/
850.4225
and
850.4250),
Tier
I
seedling
emergence
for
10
species
of
terrestrial
plant
(
122­
1/
850.4100),
and
Algal
Toxicity
(
123­
2/
850.5400).
In
addition,
the
Agency
requests
a
monitoring
study
of
runoff
from
antisapstain
facilities
to
establish
EEC's
for
risk
assessment.

The
following
data
requirement
is
reserved
for
TCMTB,
pending
the
results
of
Tier
I
testing:
Tier
II
seedling
emergence
with
10
species
of
terrestrial
plant
(
123­
1/
850.4100).
Page
62
of
66
Label
Hazard
Statements/
Use
Recommendations
The
following
ecological
effects/
environmental
risk
statements
are
required
for
TCMTB
labels:
"
This
product
is
toxic
to
fish,
aquatic
invertebrates,
oysters
and
shrimp."

"
Do
not
discharge
effluent
containing
this
product
into
lakes,
streams,
ponds,
estuaries,
oceans,
or
other
waters
unless
in
accordance
with
the
requirements
of
a
National
Pollutant
Discharge
Elimination
System
(
NPDES)
permit
and
the
permitting
authority
has
been
notified
in
writing
prior
to
discharge.
Do
not
discharge
effluent
containing
this
product
to
sewer
systems
without
previously
notifying
the
local
sewage
treatment
plant
authority.
For
guidance
contact
your
State
Water
Board
or
Regional
Office
of
the
EPA."

Antisapstain
labels
must
state:
"
Treated
lumber
must
not
be
stored
outdoors
without
precautions
to
prevent
to
prevent
leaching
by
rainfall
to
the
environment.
Suitable
precautions
include:
covering
wood
with
plastic
or
other
impervious
covering,
installation
of
berms
and
placement
of
plastic
under
the
wood
to
prevent
surface
water
runoff
away
from
the
storage
area."

12.0
REFERENCES
Accession
#
009869.
Booden,
R.
M.
1974.
Avian
Dietary
LC50,
Mallard
Duck,
Report
#
4043620.
Unpublished
data,
conducted
by
Warf
Institute
for
Buckman
Laboratories,
Memphis,
TN.

Accession
#
091624.
Knott,
W.
B.,
and
G.
Woodard.
1968a.
Busan
72
 
Safety
Evaluation
on
Bobwhite
Quail.
Unpublished
data,
conducted
by
Woodard
Research
Corp.,
for
Buckman
Laboratories,
Inc.,
Memphis,
TN.

Accession
#
091624.
Knott,
W.
B.,
and
G.
Woodard.
1968b.
Busan
72
 
Safety
Evaluation
on
Bluegill
Sunfish
and
Rainbow
Trout.
Unpublished
data,
conducted
by
Woodard
Research
Corp.,
for
Buckman
Laboratories,
Inc.,
Memphis,
TN
MRID
#
403636­
01.
Surprenant,
D.
C.
1986a.
Acute
Toxicity
of
TCMTB
to
the
Sheepshead
Minnow,
Cyprinodon
variegatus.
Unpublished
data,
conducted
by
Springborn
Bionomics,
Inc.,
for
Buckman
Laboratories,
Inc.,
Memphis,
TN
MRID
#
403363­
02.
Surprenant,
D.
C.
1987.
Acute
Toxicity
of
TCMTB
to
Mysid
Shrimp
(
Mysidopsis
bahia).
Unpublished
data,
conducted
by
Springborn
Bionomics,
Inc.,
for
Buckman
Laboratories,
Inc.,
Memphis,
TN.

MRID
#
403636­
03.
Surprenant,
D.
C.
1986b.
Acute
Toxicity
of
TCMTB
to
Embryo­
Larvae
of
the
Quahog
Clam
(
Mercenaria
mercenaria).
Unpublished
data,
conducted
by
Springborn
Bionomics,
Inc.,
for
Buckman
Laboratories,
Inc.,
Memphis,
TN.

MRID
#
415956­
01.
Long,
R.
D.,
C.
P.
Driscoll,
K.
A.
Hoxter,
and
G.
J.
Smith.
1990.
TCMTB:
A
Dietary
LC50
Study
with
the
Mallard.
Unpublished
data,
conducted
by
Wildlife
International,
Page
63
of
66
Ltd.,
for
Buckman
Laboratories,
Inc.,
Memphis,
TN.

MRID
#
415956­
02.
Long,
R.
D.,
C.
P.
Driscoll,
K.
A.
Hoxter,
and
G.
J.
Smith.
1990.
TCMTB:
A
Dietary
LC50
Study
with
the
Northern
Bobwhite.
Unpublished
data,
conducted
by
Wildlife
International,
Ltd.,
for
Buckman
Laboratories,
Inc.,
Memphis,
TN.

MRID
#
417809­
01.
Campbell,
S.
1991.
TCMTB:
An
Acute
Oral
Toxicity
Study
with
the
Northern
Bobwhite."
Unpublished
data,
conducted
by
Wildlife
International,
Ltd.,
for
Buckman
Laboratories,
Memphis,
TN
MRID
#
418042­
01.
Machado,
M.
W.
1991a.
TCMTB
 
Acute
Toxicity
to
Bluegill
Sunfish
(
Lepomis
macrochirus)
under
Flow­
through
Conditions.
Unpublished
data,
conducted
by
Springborn
Laboratories,
Inc.,
for
Buckman
Laboratories,
Inc.,
Memphis,
TN.

MRID
#
418181­
01.
Machado,
M.
W.
1991b.
TCMTB
 
Acute
Toxicity
to
Rainbow
Trout
(
Oncorhynchus
mykiss)
under
Flow­
through
Conditions.
Unpublished
data,
conducted
by
Springborn
Laboratories,
Inc.,
for
Buckman
Laboratories,
Inc.,
Memphis,
TN
MRID
#
418382­
01.
McNamara,
P.
C.
1991.
TCMTB
 
Acute
Toxicity
to
Daphnids
(
Daphnia
magna)
Under
Flow­
Through
Conditions.
Unpublished
data,
conducted
by
Springborn
Laboratories,
Inc,
for
Buckman
Laboratories,
Inc.,
Memphis,
TN.

MRID
#
422260­
01.
Collins,
M.
K.
1992b.
2­
Mercaptobenzothiazole
(
ROKON)
 
Acute
Toxicity
to
Daphnids
(
Daphnia
magna)
Under
Static
Conditions.
Unpublished
data,
conducted
by
Springborn
Laboratories,
Inc.,
for
R.
T.
Vanderbilt
Ct.,
Inc.,
Norwalk,
CT.

MRID
#
422322­
01.
Collins,
M.
K.
1992a.
2­
Mercaptobenzothiazole
(
ROKON)
 
Acute
Toxicity
to
Rainbow
Trout
(
Oncorhynchus
mykiss)
Under
Static
Conditions.
Unpublished
data,
conducted
by
Springborn
Laboratories,
Inc.,
for
R.
T.
Vanderbilt
Ct.,
Inc.,
Norwalk,
CT
MRID
#
422671­
01.
Pedersen,
C.
A.,
and
B.
R.
Helsten.
1992a.
2­
Mercaptobenzothiazole
(
ROKON):
14­
day
Acute
Oral
LD50
Study
in
Bobwhite
Quail.
Unpublished
data,
conducted
by
Bio­
Life
Associates,
Ltd.,
for
R.
T.
Vanderbilt
Co.,
Inc.,
Norwalk,
CT.

MRID
#
424285­
01.
Pedersen,
C.
A.,
and
B.
R.
Helsten.
1992b.
2­
Mercaptobenziothiazol
(
ROKON):
8­
Day
Acute
Dietary
LC50
Study
in
Bobwhite
Quail.
Unpublished
data,
conducted
by
Bio­
Life
Associates,
Ltd.,
for
R.
T.
Vanderbilt
Co.,
Norwalk,
CT.

MRID
#
425929­
01.
Rhodes,
J.
E.
1992.
Early
Life­
Stage
Toxicity
of
2­(
Thiocyanomethylthio)
benzothiazole
(
TCMTB)
to
the
Rainbow
Trout
Under
Flow­
Through
Conditions.
Unpublished
data,
conducted
b
ABC
Laboratories,
Inc.,
for
Buckman
Laboratories
International,
Inc.,
Memphis,
TN.

MRID
#
442009­
01.
Thompson,
S.
G.,
and
J.
P.
Swigert.
1996.
TCMTB:
A
14­
Day
Static­
Renewal
Toxicity
Test
with
Duckweed
(
Lemna
gibba).
Unpublished
data,
conducted
by
Wildlife
International,
Ltd.,
for
Buckman
Laboratories
International,
Inc.,
Memphis,
TN.
Page
64
of
66
Additional
References:

Aschacher
G
and
Gruendlinger
R,
2000.
Methods
to
evaluate
the
ecotoxicological
risks
of
anti­
sapstain
preservatives.
Holzforschung,
Austria
Research
and
Development.
www.
holzforschung.
at/
english/
img_
eng/
ascha200.
pdf.

Addinsoft,
2004.
XLSTAT
v7.5.
http://
www.
xlstat.
com.

.

Chew,
G.
L.,
G.
M.
Kruzynski,
and
I.
K.
Birtwell.
Behavioural
assessment
of
exposure
of
juvenile
Chinook
salmon
(
Oncorhynchus
tshawtscha)
to
sublethal
doses
of
a
toxicant.
In
Proceedings
of
the
Seventeenth
Annual
Aquatic
Toxicity
Workshop,
Nov.
5­
7,
1990,
Vancouver,
BC,
Vol.
1.
(
edited
by
P.
Chapman,
F.
Bishay,
E.
Power,
K.
Hall,
L.
Harding,
D.
Mcleay,
M.
Nassichuk
and
W.
Knapp).
Canadian
Technical
report
of
Fisheries
and
Aquatic
Sciences,
No.
1774
(
vol
1).

Karickhoff
SW,
DS
Brown,
TA
Scott,
1979.
Sorption
of
Hydrophobic
Pollutants
on
Natural
Sediments.
Water
Resources.
13:
241­
248.

Krahn
P
and
Strub
R,
1990.
Standard
Leaching
Test
for
Antisapstain
Chemicals:
Regional
Program
Report
90­
10.
Environment
Canada,
Conservation
and
Protection,
Pacific
and
Yukon
Region
North
Vancouver,
BC.

Kruzynski,
G.
M.,
and
I.
K.
Birtwell.
1990.
Some
Respiratory
Responses
of
Juvenile
Pacific
Salmon
to
the
Antisapstain
Chemical
TCMTB.
In
Proceedings
of
the
Seventeenth
Annual
Aquatic
Toxicity
Workshop,
Nov.
5­
7,
1990,
Vancouver,
BC,
Vol.
1.
(
edited
by
P.
Chapman,
F.
Bishay,
E.
Power,
K.
Hall,
L.
Harding,
D.
Mcleay,
M.
Nassichuk
and
W.
Knapp).
Canadian
Technical
report
of
Fisheries
and
Aquatic
Sciences,
No.
1774
(
vol
1).

Kruzynski,
G.
M.,
I.
K.
Birtwell,
G.
L.
Chew,
G.
E.
Piercey,
and
S.
Spohn.
1990.
An
approach
to
testing
for
ecological
relevance
using
behavioral
toxicology.
.
In
Proceedings
of
the
Seventeenth
Annual
Aquatic
Toxicity
Workshop,
Nov.
5­
7,
1990,
Vancouver,
BC,
Vol.
1.
(
edited
by
P.
Chapman,
F.
Bishay,
E.
Power,
K.
Hall,
L.
Harding,
D.
Mcleay,
M.
Nassichuk
and
W.
Knapp).
Canadian
Technical
report
of
Fisheries
and
Aquatic
Sciences,
No.
1774
(
vol
1).

Lee
R,
2004.
WLM
recommendation
regarding
chemical
generalization.
Memorandum
to
Siroos
Mostaghimi,
USEPA.
December
15,
2004.

Mineau,
P.,
B.
T.
Collins,
and
A.
Baril.
1996.
On
the
Use
of
Scaling
Factors
to
Improve
Interspecies
Extrapolation
of
Acute
Toxicity
in
Birds.
Regul
Toxicol
Pharmacol
24;
24­
29.

USEPA.
2006.
Office
of
Pesticide
Programs
internal
memorandum,
"
Aquatic
Exposure
Assessment
for
the
Use
of
the
Fungicide
of
2­
Thiocyanomethylthio)
benzothiazole
(
TCMTB)
as
a
Seed
Treatment
on
Cotton,
Wheat,
Barley,
Oats,
Rice,
Sugar
Beets,
and
Safflower,"
February
16,
2006.
Page
65
of
66
USEPA.
2004.
Overview
of
the
Ecological
Risk
Assessment
Process
in
the
Office
of
Pesticide
Programs
U.
S.
Environmental
Protection
Agency
­
Endangered
and
Threatened
Species
Effects
Determinations,
1/
23/
04.

US
EPA.
1979.
TN
2432.
Biological
Report
of
Analysis,
90+
TCMTB,
sample
MB618.
Unpublished
data,
performed
by
US
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