Document ID: EPA-HQ-OPP-2005-0062-0003
Agency: epa
Document Type: Supporting & Related Material
Title: 
Posted Date: 2006-02-22T05:00Z

UNITED
STATES
ENVIRONMENTAL
PROTECTION
AGENCY
WASHINGTON,
D.
C.
20460
OFFICE
OF
PREVENTION,
PESTICIDES
AND
TOXIC
SUBSTANCES
Date:
January
25,
2006
MEMORANDUM
SUBJECT:
Phase
2
Response
to
Error
Comments
for
the
Boric
Acid/
Sodium
Borate
Salts
TRED.
PC
Codes:
011001
(
boric
acid),
011102
(
sodium
tetraborate
decahydrate),
011110
(
sodium
tetraborate
pentahydrate),
011112
(
sodium
tetraborate
anhydrous),
011103
(
disodium
octaborate
tetrahydrate),
011107
(
disodium
octaborate
anhydrous),
011104
(
sodium
metaborate).
DP
Barcode:
DP320908
FROM:
Linnea
J.
Hansen,
Biologist
Toxicology
Branch
Health
Effects
Division
(
7509C)
AND
Jeff
Evans,
Senior
Biologist
Chemistry
and
Exposure
Branch
Health
Effects
Division
(
7509C)

THROUGH:
Louis
Scarano,
Ph.
D.,
Chief
Toxicology
Branch
Health
Effects
Division
(
7509C)

TO:
Nathan
Mottl,
CRM/
Laura
Parsons,
PM
Reregistration
Branch
I
Special
Review
and
Reregistration
Division
(
7505C)

Introduction
In
a
letter
dated
December
22,
2005
from
Tracy
Branch,
Product
Safety
Manager,
U.
S.
Borax
Inc.
submitted
comments
on
the
Tolerance
Reassessment
Eligibility
Decision
Document
(
TRED)
on
boric
acid
and
sodium
borate
salts
for
the
initial
error­
only
comment
review
prior
to
posting
of
the
document
for
public
comments.
In
this
Phase
2
Response,
the
Health
Effects
Division
(
HED)
has
reviewed
the
error
comments
submitted
by
this
Registrant.
The
comments
have
been
addressed
by
Linnea
Hansen
and
Jeff
Evans.
The
HED
responses
to
each
comment
are
shown
below.
As
appropriate,
error
2
corrections
have
been
incorporated
into
the
revised
TRED
document,
which
will
be
posted
for
public
comment.

U.
S.
Borax
Comments
and
HED's
Response
to
the
Comments
A.
Typographical
Errors
1.
Comment:
Appendix
3,
correct
NOAEL
to
8.8
mg/
kg/
day
from
8.9
mg/
kg/
day.

Agency
Response:
The
NOAEL
value
has
been
corrected
in
the
TRED
document.

2.
Comment:
Table
6.3c,
in
Footnote
"
a"
the
equation
for
calculation
of
ADD
is
missing
a
term
for
water
concentration
(
Cw).

Agency
Response:
Footnote
"
a"
in
the
TRED
document
has
been
corrected
to
include
a
term
for
water
concentration.

3.
Comment:
Table
6.3d
footnotes
c
and
d
are
incorrectly
assigned
between
the
exposure
scenario
and
the
label
description.

Agency
Response:
Footnotes
"
c"
and
"
d"
in
the
TRED
document
have
been
correctly
assigned.

B.
Computational
Errors
1.
Comment:
Calculations
for
exposure
as
provided
in
Table
6.3a
show
incorrect
MOEs:
exposure
calculations
are
correct
but
the
endpoint
value
was
incorrect
at
400
mg/
kg/
day
instead
of
8.8
mg/
kg/
day.

Agency
Response:
MOE
calculations
have
been
corrected
using
an
endpoint
of
8.8
mg/
kg/
day.

2.
Comment:
In
Table
6.3b,
the
adjusted
ADR
for
sodium
tetraborate
decahydrate
and
sodium
tetraborate
appears
to
be
divided
instead
of
multiplied
by
the
boron
content
(%).

Agency
Response:
The
correct
values
have
been
provided
in
Table
6.3b
of
the
TRED.

3.
Comment:
In
Table
6.3b,
the
Frequency
of
Use
(
events/
yr)
value
(
52)
is
for
dermal
exposure
rather
than
inhalation
(
correct
value
312).

Agency
Response:
Frequency
of
Use
calculations
for
Table
6.3b
has
been
corrected.

4.
Comment:
In
Table
6.3d,
ADD
values
provided
in
the
table
are
half
of
what
they
should
be.

Agency
Response:
ADD
values
in
Table
6.3d
have
been
corrected.
3
5.
Comment:
The
Registrant
obtained
different
values
for
LADD,
ADD
and
ADR
for
several
exposure
scenarios
(
Appendix
4)
when
using
the
Consumer
Exposure
Model
(
CEM)
as
referenced
in
the
Agency
website.

Agency
Response:
CEM
does
more
complex
calculations
than
those
offered
by
the
registrant.
For
inhalation
exposures,
it
is
not
possible
to
calculate
the
ADD
using
the
ADD
equation
provided
in
the
CEM
model
and
the
ADC
from
the
model
output.
This
is
because
the
ADC
in
the
CEM
output
is
an
average
concentration
over
the
course
of
a
day
and
not
an
event.
The
model
calculates
the
ADD
using
an
integrated
equation
to
account
for
the
change
in
air
concentration
over
time,
movement
into
and
out
of
the
room
and
changes
in
breathing
rates.
However,
for
these
cases,
the
same
breathing
rate
was
used
for
the
before
and
after
event
time
periods.
A
simplified
calculation
(
0.0103
mg/
m3
*
(
0.55
m3/
hr*
24
hr/
day))/
71.8
kg
=
1.89
mg/
kg/
day.
The
same
holds
true
for
the
ADR
calculations.

C.
Additional
and
Pertinent
Studies
Comments
on
the
hazard
characterization
of
boric
acid
and
sodium
borate
salts
are
discussed
below.
Several
of
the
comments
provided
by
the
Registrant
pertained
to
substantive
issues
such
as
determination
of
study
acceptability
or
review
of
additional
studies.
These
comments
will
be
addressed
following
the
public
comment
period
on
this
document,
as
indicated
below
for
each
individual
comment.

1.
Comment:
The
Registrant
noted
that
an
additional
acute
inhalation
study
in
the
rat
was
submitted
(
MRID
43500701
and
an
addendum
submitted
August
13,
1996)
that
would
place
boric
acid
in
Toxicity
Category
III
instead
of
II,
and
considered
a
28­
day
inhalation
toxicity
study
in
the
rat
(
new
study
required
in
the
TRED)
unnecessary.

Agency
Response:
HED
will
review
the
acute
inhalation
study
and
will
respond
to
the
separate
issue
of
requiring
a
28­
day
rat
inhalation
toxicity
study
following
the
public
comment
period.

2.
Comment:
The
Registrant
questioned
the
selection
of
the
endpoint
for
risk
assessment,
8.8
mg/
kg/
day
in
the
dog
based
on
testicular
effects,
due
to
various
issues
with
the
quality
of
the
dog
studies
used
to
derive
the
endpoint.
It
was
noted
that
other
regulatory
groups
used
a
developmental
toxicity
study
for
endpoint
selection
(
based
on
a
NOAEL
of
9.6
mg/
kg/
day)
due
to
these
issues.

Agency
Response:
While
acknowledging
questions
regarding
aspects
of
the
conduct
of
the
dog
studies
used
to
derive
the
endpoint
of
8.8
mg/
kg/
day,
the
Agency
has
considered
the
available
data
and
determined
that
these
studies
are
acceptable
for
regulatory
purposes.
In
1995,
HED
reevaluated
these
studies
along
with
the
developmental
toxicity
studies
and
determined
that
the
study
may
be
used
and
considered
"
co­
critical"
with
the
developmental
toxicity
study
in
the
rat
(
memorandum
from
George
Ghali
to
Robert
Forrest
dated
June
12,
1995).
Use
of
this
study
was
upheld
by
the
HED
RARC
4
(
memorandum
from
Linnea
J.
Hansen
and
Jeff
Evans
to
Laura
Parsons
and
Nathan
Mottl
dated
November
14,
2005).
The
dog
endpoint
was
selected
as
a
slightly
more
conservative
endpoint,
although
practically
speaking,
there
is
not
a
significant
difference
between
the
two
values.

3.
Comment:
The
Registrant
agreed
with
the
Toxicity
Category
for
acute
toxicity
in
dogs,
although
values
differed
slightly
from
those
in
the
TRED.
It
was
also
requested
that
the
TRED
mention
that
"
the
dogs
all
vomited
and
therefore
there
is
a
limit
to
how
high
you
can
test
a
dog."

Agency
Response:
The
Agency
will
respond
to
this
comment
following
the
public
comment
period.

4.
Comment:
The
Registrant
submitted
an
Amendment
to
the
Final
Report
of
an
Unscheduled
DNA
synthesis
study,
classified
as
"
Unacceptable,"
to
provide
additional
information
to
upgrade
the
study
to
"
Acceptable."

Agency
Response:
The
Agency
will
review
the
submitted
amendment
and
respond
following
the
public
comment
period.

5.
Comment:
The
Registrant
submitted
clarification
of
animal
survival
values
in
the
two
year
dietary
study
in
the
rat
on
borax,
which
had
a
discrepancy
between
the
value
presented
in
the
study
report
(
76.9%)
and
the
data
itself
(
64%)
for
mid
dose
male
survival.
The
correct
value
should
be
64%.
This
study
report
was
conducted
prior
to
GLP
and
was
therefore
not
subject
to
quality
checks.

Agency
Response:
The
Agency
agrees
with
this
comment
and
the
study
summary
in
the
TRED
has
been
amended
accordingly.

6.
Comment:
A
dermal
absorption
reference
mentioned
in
the
IRIS
review
was
submitted.

Agency
Response:
The
Agency
notes
the
submission
of
this
study,
which
does
not
affect
the
conclusions
of
this
TRED.

7.
Comment:
The
Registrant
questioned
the
relevance
of
the
NOAEL
used
for
risk
assessment
for
exposure
to
children.

Agency
Response:
Because
this
is
a
substantive
comment
addressing
endpoint
selection,
rather
than
an
error­
only
comment,
it
will
be
addressed
by
the
Agency
following
the
public
comment
period.

8.
Comment:
The
Registrant
requested
details
of
incident
case
reports
cited
in
the
TRED,
Section
5.1
Incident
Reports
("
Among
adults,
there
have
been
incidents
with
significant
toxicity
from
breathing
dusts
that
were
airborne.
These
incidents
are
usually
due
to
over­
application
by
inexperienced
applicators").
5
Agency
Response:
A
copy
of
the
memorandum
on
boric
acid
incident
reports
(
obtained
from
the
EPA
Incident
Data
System)
will
be
placed
into
the
docket
for
the
public
comment
on
this
risk
assessment.

9.
Comment:
The
Registrant
provided
an
additional
reference
(
Rainey
et
al.,
1999)
on
human
daily
boron
intake.

Agency
Response:
The
submitted
reference
will
reviewed
and
the
information
addressed
by
the
Agency
following
the
public
comment
period.