Document ID: EPA-HQ-OPP-2004-0370-0120
Agency: epa
Document Type: Supporting & Related Material
Title: 
Posted Date: 2005-10-18T04:00Z

1
UNITED
STATES
ENVIRONMENTAL
PROTECTION
AGENCY
WASHINGTON,
D.
C.
20460
OFFICE
OF
PREVENTION,
PESTICIDES
AND
TOXIC
SUBSTANCES
September
28,
2005
Memorandum
SUBJECT:
Endothall
and
Salts:
Occupational
and
Residential
Exposure
Assessment
of
Antimicrobial
Uses
for
the
Reregistration
Eligibility
Decision
Document.
PC
Code
038905,
RED
Case
No.
2245,
DP
Barcode
D313928.

FROM:
Tim
Leighton,
Environmental
Scientist
Antimicrobials
Division
Through:
Mark
Hartman,
Branch
Chief,
Regulatory
Management
Branch
II
Antimicrobials
Division
TO:
Ben
Chambliss,
Chemical
Review
Manager
Antimicrobials
Division,
and
Mika
Hunter,
Chemical
Review
Manager
Special
Review
&
Reregistration
Division
The
Health
Effects
Division
(
HED)
has
the
lead
for
the
endothall
and
salts
preliminary
risk
assessment
for
the
Reregistration
Eligibility
Decision
(
RED)
document.
The
antimicrobial
use
of
endothall
is
based
on
PC
code
038905,
mono(
N,
N­
dimethylalkylamine)
salt
of
endothall.
This
memorandum
provides
a
standalone
review
of
the
non­
dietary
antimicrobial
use
of
endothall,
which
is
limited
to
industrial
cooling
water
systems
(
i.
e.,
recirculating
and
once
through
cooling
water
systems,
EPA
Reg.
No.
4581­
380).

EXECUTIVE
SUMMARY
The
Antimicrobials
Division
(
AD)
assessed
the
occupational
antimicrobial
use
of
endothall
and
salts
using
the
toxicological
data
from
the
Health
Effects
Division
(
HED).
For
a
complete
review
of
the
endothall
and
salts
risk
assessment,
the
reader
is
referred
to
the
HED
risk
assessment
chapter
(
D296791).
The
results
of
the
occupational
assessment
of
the
antimicrobial
use
(
i.
e.,
to
control
mollusks
in
industrial
water
systems)
indicates
that
the
inhalation
margin
of
exposures
(
MOEs)
to
the
handlers
of
endothall
are
not
of
concern
(
i.
e.,
inhalation
MOEs
are
greater
than
target
MOE
of
100).
No
dermal
toxicological
endpoints
were
identified.
Although
postapplication
worker
exposure
to
endothall
is
not
expected,
there
is
the
potential
for
swimmer
exposure
in
endothall
treated
water.
Risks
to
swimmers
have
been
assessed
by
HED
at
higher
rates
than
those
for
the
industrial
cooling
water
systems,
and
therefore,
AD
has
not
provided
2
separate
estimates.
HED's
conclusions
are
that
the
swimmer
risks
are
not
of
concern.

1.
Introduction
The
risk
assessment
for
the
agricultural
uses
of
endothall
has
been
prepared
by
the
Health
Effects
Division
(
HED).
The
reader
is
referred
to
the
HED
risk
assessment
for
an
in
depth
analysis
of
the
toxicological
and
residue
chemistry
of
endothall.
This
memorandum
includes
an
inhalation
assessment
of
the
occupational
exposure
and
risk
for
the
antimicrobial
use
(
i.
e.,
cooling
water).
The
antimicrobial
use
that
is
assessed
in
this
memorandum
is
classified
under
the
Use
Site
Category
(
USC)
industrial
processes.
Endothall
is
used
to
control
fresh
and
salt
water
mollusks
in
industrial
cooling
water
systems
(
both
recirculating
and
once
through).
According
to
the
one
registered
antimicrobial
label
for
endothall
(
EPA
Reg.
No.
4581­
380),
the
product
is
metered
directly
into
the
water
system.

No
exposure
data
have
been
submitted
in
support
of
the
endothall
antimicrobial
use.
Therefore,
a
screening­
level
handler
assessment
has
been
provided
using
surrogate
data
from
the
Chemical
Manufacturers
Association
(
CMA).
Postapplication
worker
exposure
is
not
expected
for
industrial
cooling
water
systems.

2.0
Toxicological
Endpoints
of
Concern
The
toxicological
endpoints
selected
for
endothall
are
summarized
in
Table
1.
For
a
complete
review
of
the
toxicological
endpoints
selected
for
endothall,
the
reader
is
referred
to
HED's
endothall
RED
chapter
(
D296791).
Endothall
is
not
classified
for
carcinogenic
potential.

Table
1:
Summary
of
Toxicology
Endpoint
Selection
for
Endothall
Pertaining
to
Antimicrobial
Uses
Exposure
Scenario
Dose
Used
in
Risk
Assessment
Special
FQPA
SF
and
Level
of
Concern
for
Risk
Assessment
Study
and
Toxicological
Effects
Short­
Term
Dermal
(
1
to
30
days)

Intermediate
(
1
to
6
months)­
and
Long­
Term
(>
6
months)
Dermal
No
dermal
endpoint
was
selected.
A
21­
day
dermal
toxicity
study
was
submitted
and
reviewed
based
on
dermal
irritation
and
body
weight
gain
inhibition.
Body
weight
losses
were
observed
in
females
at
Days
14
and
20
and
therefore
a
LOAEL
of
30
mg/
kg/
day
was
established
for
systemic
toxicity.
No
NOAEL
for
systemic
toxicity
was
established.
There
were
also
severe
local
dermal
effects
at
30
mg/
kg/
day
based
on
erythema,
edema,
fissuring
of
the
dose
site
and
sloughing
of
the
skin
at
the
dose
sites.
No
NOAEL
for
dermal
irritation
was
established.
Because
of
the
systemic
and
local
effects
were
co­
occurrent,
it
is
more
likely
that
the
weight
loss
was
a
consequence
of
the
severe
local
toxicity.
Therefore
Risk
Assessment
Review
Committee
(
RARC)
determined
that
endothall
should
be
regulated
as
a
severe
dermal
irritant
and
not
on
systemic
effects,
and
recommended
against
conducting
a
dermal
risk
assessment
because
the
severe
localized
irritation
effects
of
endothall
on
the
skin
would
be
self­
limiting
as
to
dermal
exposures.
3
Table
1:
Summary
of
Toxicology
Endpoint
Selection
for
Endothall
Pertaining
to
Antimicrobial
Uses
Exposure
Scenario
Dose
Used
in
Risk
Assessment
Special
FQPA
SF
and
Level
of
Concern
for
Risk
Assessment
Study
and
Toxicological
Effects
Short­
Term
Inhalation
(
1
to
30
days)
Offspring
NOAEL
=
9.4
mg/
kg/
day
(
inhalation
absorption
rate
=
100%)
Residential
LOC
for
MOE
=
100
Occupational
LOC
for
MOE
=
100
2­
generation
reproduction
study
in
rats
[
adult]
LOAEL
=
2
mg/
kg/
day
based
on
proliferative
lesions
of
the
gastric
epithelium
in
both
sexes
Intermediate­
(
1
to
6
months)
and
Long
(>
6
months)
­
Term
Inhalation
LOAEL=
2
mg/
kg/
day
Residential
LOC
for
MOE
=
300
Occupational
LOC
for
MOE
=
300
2­
generation
reproduction
study
in
rats
[
adult]
LOAEL
=
2
mg/
kg/
day
based
on
proliferative
lesions
of
the
gastric
epithelium
in
both
sexes
Cancer
(
oral,
dermal,
inhalation)
Not
likely
to
be
carcinogenic
to
humans
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
The
acute
toxicity
data
for
endothall
are
summarized
in
Table
2.

Table
2:
Acute
Toxicity
of
Endothall
Guideline
No.
Study
Type
MRID
Number
Results
Toxicity
Category
870.1100
(
§
81­
1)
Acute
Oral
42289201
LD50
=
males
50.2,
females
44.4
mg/
kg
I
870.1200
(
§
81­
2)
Acute
Dermal
42289202
LD50
=
males
>
2000,
females
>
2000,
combined
>
2000
mg/
kg
III
870.1300
(
§
81­
3)
Acute
Inhalation
42169501
LC50
=
males
1.27,
females
2.20,
combined
1.51
m/
L
III
870.2400
(
§
81­
4)
Primary
Eye
Irritation
422889203
extremely
irritating
lethal
4/
6
rabbits
I
870.2500
(
§
81­
5)
Primary
Skin
Irritation
42289204
unacceptable
study
I
a
870.2600
(
§
81­
6)
Dermal
Sensitization
41871901
positive
N/
A
a
Endothall
has
been
shown
to
be
a
skin
irritant
in
a
preliminary
range
finding
study
of
the
dermal
absorption
study
(
MRID
42169503)
at
single
doses
of
50

g/
cm2
and
higher
and
in
the
21­
day
dermal
toxicity
study
(
MRID
43465201)
after
one
application
at
doses
of
30
mg/
kg
or
higher.
This
information
is
considered
sufficient
to
classify
endothall
as
a
severe
dermal
irritant.

3.0
Handler
Assessment
All
of
the
endothall
antimicrobial
applications
are
for
industrial
cooling
water
systems
4
(
recirculating
and
once
through)
to
control
mollusks,
EPA
Reg.
No.
4581­
380.
There
are
no
residential
use
patterns
for
the
antimicrobial
uses.
The
label
directions
indicate
that
the
product
should
be
applied
to
achieve
a
0.3
to
3.0
ppm
endothall
(
2.4
to
24
gallons
of
a
2
lb
endothall
per
gallon
product
per
1,000,000
gallons
of
water).
The
label
also
indicates
that
the
continuous
feed
should
be
maintained
for
6
to
144
hours.
Although
a
continuous
feed
is
a
daily
operation,
handlers
treating
water
systems
are
expected
to
apply
endothall
(
i.
e.,
change
couplers
for
containers
of
endothall)
on
a
limited
basis
(
1
to
6
days
based
on
label
directions)
and
are
believed
to
be
represented
by
a
short­
term
(
1
to
30
days)
exposure
duration
(
e.
g.,
applications
to
control
mollusks
should
not
be
a
monthly
occurrence).
Clarification
should
be
added
to
the
label
providing
some
indication
on
how
often
this
treatment
should
be
applied
(
e.
g.,
yearly).

At
this
time,
a
screening­
level
assessment
has
been
developed
for
the
recirculating
use
as
well
as
the
once
through
use.
Recirculating
cooling
water
systems
can
vary
tremendously
in
volume
and
are
believed
to
be
generally
less
than
50
million
gallons.
The
range
of
volume
assessed
for
the
large
scale
once
through
power
generators
(
label
does
not
restrict
the
product
to
power
generators
but
they
represent
the
high
end)
includes
2
to
500
million
gallons.
The
2
million
gallons
were
selected
as
the
low
range
based
on
it
representing
the
"
de
minimus"
flow
for
EPA's
Cooling
Water
Intake
Structure
Rule
(
40CFR125.90).
Although
a
few
power
generators
may
have
water
flows
of
approximately
1
to
3
billion
gallons,
these
few
utilities
are
atypical.
EPA
assumed
that
if
the
large
utilities
apply
endothall
it
would
be
applied
as
a
continuous
feed
over
6
days
as
per
the
label
recommendations
(
i.
e.,
500
million
gallons
treated/
6
days
=
83.3
million
gallons
of
water
treated
per
day).

EPA
does
not
have
a
specific
surrogate
exposure
scenario
for
once
through
or
recirculating
cooling
water
systems,
however,
exposure
data
for
pumping
liquids
are
available.
The
exposure
data
for
pumping
liquids
that
are
available
to
EPA
include
data
from
the
CMA
study.
The
pumping
liquids
data
in
the
CMA
study
are
used
to
develop
a
screening­
level
assessment.
The
most
representative
scenario
available
from
the
CMA
data
base
for
pumping
liquids
into
large
water
systems
is
for
the
pulp
&
paper
industry.

Since
no
dermal
toxicological
endpoints
of
concern
were
identified
for
endothall,
dermal
exposures
are
not
estimated.
The
inhalation
unit
exposure
(
UE)
for
pumping
liquids
in
the
pulp
&
paper
scenario
is
0.000265
mg/
lb
ai.
The
exposures
are
assessed
for
various
amounts
of
endothall
potentially
handled
because
the
volume
of
water
in
industrial
water
systems
can
vary
tremendously.
Table
3
presents
the
potential
inhalation
exposure
for
pumping
liquids
into
recirculating
systems
as
well
as
a
range
of
once
through
systems.
Inhalation
MOEs
are
also
provided
(
only
inhalation
risks
have
been
presented
because
no
dermal
toxicological
endpoint
of
concern
has
been
identified).
5
Table
3.
Potential
Short­
term
Exposure
and
Risk
to
Endothall
During
Closed
Loading
into
Industrial
Water
Systems.

Use
Inhalation
Unit
Exposures
(
mg/
lb
ai)
a
Concentration
of
Endothall
(
ppm)
b
Application
Rate
(
lb
ai/
million
gallons
water)
c
Volume
of
Cooling
Water
d
Daily
Inhalation
Dose
(
mg/
kg/
day)
e
Short­
term
Inhalation
MOE
f
Recirculating
Water
Systems
0.3
4.8
0.0009
10,000
Liquid
Pump
0.000265
3
48
Less
than
50
million
gallons
0.009
1,000
Once
Through
Cooling
Water
Systems
0.3
4.8
3.6E­
5
260,000
3
48
2
million
gallons
0.00036
26,000
0.3
4.8
0.0015
6,200
Liquid
Pump
0.000265
3
48
500
million
gallons
over
6
days
0.015
620
a
Inhalation
Unit
Exposure
(
UE)
is
from
the
CMA
data
base
for
pulp
&
paper.
b
Concentration
of
endothall
in
cooling
water
based
on
the
range
reported
in
EPA
Reg.
No.
4581­
380
(
i.
e.,
0.3
to
3
ppm).
c
Application
rate
is
based
on
EPA
Reg.
No.
4581­
380
where
0.3
or
3
ppm
requires
2.4
or
24
gal
of
product
x
2
lb
endothall
per
gal
of
product
per
1,000,000
gallons
of
cooling
water.
d
Volume
of
cooling
water
based
on
a
range
of
flow
from
large
power
generation
utilities.
e
Inhalation
Dose
(
mg/
kg/
day)
=
Inhalation
UE
(
mg/
lb
ai)
x
pounds
endothall
per
million
gallons
of
water
x
number
of
million
gallons
per
day
x
1/
70kg
BW.
f
Inhalation
MOE
=
NOAEL
/
Dose.
Where
short­
term
NOAEL
is
9.4
mg/
kg/
day
based
on
an
oral
study.
Target
MOE
is
100.
6
4.0
Postapplication
Assessment
4.1
Occupational
The
potential
for
postapplication
inhalation
exposure
to
endothall
is
expected
to
be
negligible
because
of
the
relatively
low
vapor
pressure
(
2.09
x
10­
5
mm
Hg
at
24.3
degrees
C)
and
aerosol
generation
is
not
expected
in
the
vicinity
of
workers.

4.2
Residential/
Bystander
The
potential
for
short­
term
postapplication
exposure
(
i.
e.,
during
swimming
in
treated
rivers/
lakes)
to
adults
and/
or
children
exists
for
the
once
through
cooling
water
use.
HED
has
presented
a
swimmer
risk
assessment
for
the
endothall
surface
water
applications
(
D296789,
see
Section
3.2.2
in
HED's
report).
HED's
assessment
is
based
on
the
labeled
aquatic
herbicide
use
applied
directly
to
surface
water
at
a
concentration
of
5
ppm.
HED
estimated
the
oral
exposure
to
children
in
the
6
to
10
age
group
and
adults
using
the
SWIMODEL.
HED's
assessment
is
believed
to
represent
the
high
end
of
the
risk
for
the
once
through
cooling
water
application
because
of
the
direct
application
assessed
(
i.
e.,
no
dilution
assumed)
and
the
aquatic
use
has
a
higher
application
concentration
(
i.
e.,
5
ppm
versus
3
ppm
for
the
once
through
use).
The
estimated
short­
term
MOEs
for
the
oral
route
are
280
and
900
for
the
children
and
adults,
respectively.
These
short­
term
MOEs
are
not
of
concern
(
i.
e.,
target
MOE
is
100).
Only
the
short­
term
assessment
is
believed
to
be
relevant
for
the
once
through
use
because
of
the
intermittent
nature
of
the
application
and
dilution
in
surface
water
bodies.
Inhalation
exposure
is
expected
to
be
minimal
because
of
the
low
vapor
pressure.

5.0
Risk
Characterization
Chemical­
specific
exposure
data
were
not
available
to
assess
the
antimicrobial
uses
of
endothall.
Therefore,
surrogate
data
from
the
CMA
data
base
were
used
to
generate
screeninglevel
occupational
handler
risk
estimates.
The
surrogate
data
available
to
assess
the
handlers
is
believed
to
be
representative
of
the
closed
metering
system,
but
confirmatory
exposure
data
are
needed
to
verify
the
accuracy
of
extrapolating
to
large
scale
closed
systems.
The
section
below
summarizes
the
uncertainties
in
the
assessment.

Summary
of
Uncertainties
AD
has
used
the
best
available
surrogate
exposure
data
from
CMA
to
develop
a
screening­
level
assessment
for
the
handlers
of
endothall.
The
following
uncertainties
should
be
considered
by
the
regulatory
risk
managers
during
the
decision
making
process:

$
Specific
inhalation
unit
exposures
are
not
available
for
once
through
cooling
water
systems
(
i.
e.,
large
volumes
of
chemical).
Nonetheless,
the
data
from
CMA
for
pulp
&
paper
is
a
reasonable
surrogate
for
this
type
of
closed
loading
system.
Although
the
7
CMA
data
are
only
represented
by
7
replicates,
the
exposure
values
are
similar
to
closed
loading
of
pesticides
in
the
Pesticide
Handlers
Exposure
Database
(
PHED)
 
CMA
data
are
3x
higher
than
the
PHED
value,
and
therefore,
more
conservative.
Additional
exposure
data
should
be
collected
to
confirm
the
estimates
for
large
scale
continuous
feed
closed
loading
applications.

$
The
once
through
cooling
water
flow
volumes
for
power
generation
are
large
(
e.
g.,
500
million
gallons
assessed).
It
is
unknown
if
these
utilities
actually
use
endothall
but
there
are
not
label
restrictions
on
flow
volumes.
Nonetheless,
this
screening­
level
assessment
and
the
inhalation
risks
are
not
of
concern
at
these
higher
flows.

$
The
toxicological
endpoints
selected
by
the
Health
Effects
Division
(
EPA/
OPP/
HED)
have
been
used
in
this
assessment.
Any
changes
to
the
HED
endpoints
in
the
future
will
need
to
be
incorporated
into
this
review.

$
In
a
letter
from
Elf
Atochem
(
Davis
2000),
dated
January
17,
2000,
Mr.
Davis
indicated
that
the
following
statement
would
be
removed
from
the
label:
"
EVAC
Biocide
has
also
shown
potential
for
treating
service
water,
auxiliary
water,
waste
water,
influent
and
fire
protection
water
systems."
However,
the
current
label,
dated
October
10,
2002,
still
has
this
statement.
These
uses
have
not
been
assessed
in
this
risk
assessment
because
they
are
believed
to
be
on
the
label
in
error
and
the
label
contains
no
application
rates
to
assess
the
use.
This
statement
should
be
deleted
from
the
label.

6.0
References
Davis
C.
2000.
EVAC
Biocide,
EPA
Reg.
No.
4581­
380,
Application
for
Label
Amendment.
In
a
letter
from
Christopher
Davis
(
Elf
Atochem
North
America,
Inc.)
to
Marshall
Swindell,
PM33
(
USEPA/
OPP/
AD),
dated
January
17,
2000.

USEPA.
2005.
Endothall:
HED
Chapter
of
the
Reregistration
Eligibility
Decision
Document
(
RED),
draft
dated
January
3,
2005.
PC
Code:
038901,
038904,
and
038905,
Case
#:
2245,
DP
Barcode:
D296791.