U.
S.
Borax
Inc.
26877
Tourney
Road
Valencia,
CA
91355
(
661)
287­
5400
Nathan
Mottl
Chemical
Review
manager
US
EPA
(
7508C)
1200
Pennsylvania
Avenue,
NW
Washington,
DC
20460
December
22,
2005
Re.
Boric
Acid/
Sodium
Salts:
HED
Chapter
of
the
Tolerance
Reassessment
Eligibility
Decision
Document
(
TRED)

Dear
Mr.
Mottl,

Thank
you
for
the
opportunity
to
review
the
TRED
risk
assessment
document
prior
to
posting
for
public
comments.
You
have
requested
that
Borax
Inc.
reply
on:
1)
Errors
such
as
mathematical,
computational
and
typographical
2)
Confidential
business
information
(
CBI)
and
3)
Pertinent
completed,
pending,
or
planned
studies
and
other
sources
of
information
In
reply
we
have
noted
typographical
and
computational
errors
as
well
as
presenting
comments
regarding
pertinent
data.
We
do
not
see
any
confidential
business
information
in
this
report.
We
do
have
additional
comments
we
would
like
to
submit,
but
they
may
not
be
appropriate
for
this
stage
of
the
review
process.

Borax
Inc.
has
copies
of
most
of
the
public
literature
references
mentioned
in
this
reply.
Should
you
have
any
questions
feel
free
to
contact
me.

Tracy
Branch
Product
Safety
Manager
(
661)
287­
5435
Trcay.
branch@
borax.
com
The
following
references
are
attached:

MRID
53400701,
Wnorowski,
G.
Acute
inhalation
toxicity
limit
on
boric
acid
MG
Test
Product
Safety
Labs,
US,
East
Brunswick,
New
Jersey
08816,
Study
­
5257.
Unpublished
report
to
U.
S.
Borax.
1997
plus
Robust
summary
Wnorowski,
G.,
(
1994),
Acute
inhalation
toxicity
limit
test
on
boric
acid.
Product
Safety
Labs,
US,
East
Brunswick,
New
Jersey,
0881;
Study
­
3311.
Unpublished
report
to
U.
S.
Borax.
Boric
Acid
/
Sodium
Salts
TRED
 
Comments
December
22,
2005
Page
2
of
9
Robust
Summary
Acute
Toxcity
Inhalation
Boric
Acid
.
doc
Robust
Summary
Subchronic
2
year
Dogs
Boric
acid.
doc
Robust
Summary
Subchronic
2
year
Dogs
Tetraborates.
doc
Robust
Summary
Chronic
rat
Boric
acid.
doc
Robust
Summary
Chronic
Rat
Tetraborates.
doc
Bakke
J
P
(
1991).
Evaluation
of
the
potential
of
boric
acid
to
induce
unscheduled
DNA
synthesis
in
the
in
vitro
hepatocyte
DNA
repair
assay
using
the
male
F­
344
Rat.
SRI
International,
Study
No.
2389­
V500­
91,
23
August
1991;
plus
Amendment
1
to
the
Original
Report,
May
20,
1992,
Menlo
Park,
CA.
Unpublished
Report
to
US
Borax
Inc.

Hui,
X,
Wester,
RC
and
Maibach,
HI,
(
1996)
In
Vivo
Percutaneous
Absorption
of
Boric
Acid,
Borax
and
Octaborate
Tetrahydrate
(
DOT)
in
Man.
Unpublished
Report
to
U.
S.
Borax
Inc.,
Study
Number
H832­
11830­
01,
November
12.
***

Rainey,
C.
J.,
Nyquist,
L.
A.,
Christensen,
R.
E.,
Strong,
P.
L.,
Culver,
B.
D.,
and
Coughlin,
J.
C.
1999.
Daily
boron
intake
from
the
American
diet.
J.
Am.
Diet
Assoc.
99(
3),
335­
340.

***
submitted
in
hard
copy
only
­
file
is
too
large
to
submit
electronically
Typographical
Errors
1.
Appendix
3
which
provides
additional
detailed
information
for
the
MOE
calculation
also
lists
the
wrong
NOAEL
(
e.
g.
8.9
mg
B/
kg­
day)
in
the
footnote
(
d)
for
determining
the
MOE
rather
than
the
defined
value
of
8.8
mg
B/
kg­
day.

2.
Footnote
"
a"
in
table
6.3c
that
summarizes
oral
exposure
ADD
does
not
provide
all
the
terms.
It
is
missing
a
term
for
water
concentration
(
Cw).

3.
Also,
the
footnotes
in
table
6.3d
are
not
correctly
assigned
(
footnotes
c
and
d)
between
the
exposure
scenario
and
label
description.

Computational
Errors
1.
6.3.1.1
Residential
Handler
Exposure
Scenarios

Residential
Handler
Inhalation
Exposure
Calculations
for
exposure
provided
in
Table
6.3a
are
correct
except
for
the
final
step
to
calculate
MOE.
It
appears,
from
back
calculating
the
values,
that
the
MOE
values
were
developed
by
using
a
NOAEL
of
400
mg
B/
kg­
day
rather
than
8.8
mg
B/
kg­
day
as
defined
in
the
toxicology
section
and
in
the
table
footnote
(
b).
MOE
has
been
recalculated
for
each
scenario
and
are
provided
in
the
accompanying
excel
spreadsheet
(
worksheet:
Residential
Handler
Exposure).
The
new
values
ranged
between
800
and
5,600,000.
Boric
Acid
/
Sodium
Salts
TRED
 
Comments
December
22,
2005
Page
3
of
9
2.
There
are
regular
inconsistencies
in
both
table
6.3b
and
corresponding
Appendix
(
4)
that
provides
input
and
output
information
for
the
Consumer
Exposure
Model.
For
example:


In
table
6.3b,
the
Adjusted
ADR
(
acute
dose
rate)
for
sodium
tetraborate
decahydrate
and
sodium
tetraborate
appears
to
be
divided
by
the
boron
content
(%)
rather
than
multiplied.


In
table
6.3b,
the
Frequency
of
Use
(
events/
yr)
values
of
52
are
for
dermal
exposure
and
not
inhalation
which
is
the
defined
exposure
pathway
for
this
table.
The
correct
values
should
be
312
for
the
two
scenarios
that
list
52.


A
recalculation
of
LADD,
ADD
or
ADR
for
the
different
exposure
scenarios
(
Appendix
4)
using
the
Consumer
Exposure
Model
(
CEM)
that
is
referenced
by
http://
www.
epa.
gov/
opptintr/
exposure/
docs/
efastman.
pdf
provided
estimated
values
different
than
those
used
to
calculate
the
MOE
by
orders
of
magnitude.
See
Examples
A
and
B
below.

Example
A
The
estimated
ADD
for
scenario
1;
sodium
tetraborate
decahydrate
and
general
purpose
cleaner.

ADD
=
0.0103
mg/
m3
*
0.55
m3/
hr
*
300
events/
yr
*
0.667
hrs/
event
*
57
yrs
*
0.07
/
71.8
kg
body
weight
*
57
yrs
*
365
days/
yr
ADD
=
0.00000303
mg/
kg­
day
Example
B
The
estimated
ADR
for
scenario
1;
sodium
tetraborate
decahydrate
and
general
purpose
cleaner.

ADR
=
0.00221
mg/
m3
*
0.55
m3/
hr
*
300
events/
yr
*
1.42
hrs/
event
*
57
yrs
*
0.13
/
71.8
kg
body
weight
*
1
day
ADR
=
0.053
mg/
kg­
day
Adjusted
ADR
=
0.053
mg/
kg­
day
*
11.34%
B
Adjusted
ADR
=
0.006
mg
B/
kg­
day
MOE
=
8.8
mg
B/
kg­
day
/
0.006
mg
B/
kg­
day
MOE
=
1467

Although
the
MOE
appear
to
be
correct,
the
corresponding
ADD
values
provided
in
table
6.3d
appear
to
be
calculated
using
an
additional
factor
of
50%
as
all
of
the
values
presented
are
half
of
what
they
should
be.
See
attached
excel
document,
Table:
Children­
Mouth.
Boric
Acid
/
Sodium
Salts
TRED
 
Comments
December
22,
2005
Page
4
of
9

Calculations
for
inert
ingredient
(
boric
acid)
in
general
purpose
cleaner
is
incorrect
for
ADR
as
previously
described
above
in
section
6.3.1.1
under
Residential
Handler
Exposure
to
Consumer
Use
(
non­
pesticidal)
section.
See
table
6.3b
and
Appendix
5.

It
is
recommended
that
each
of
the
values
in
tables
6.3b
and
6.3c
be
verified
for
accuracy.

Additional
and
Pertinent
Data
/
Studies
We
have
some
specific
comments
to
make
concerning
conclusions
made
in
TRED
in
the
absences
of
some
data
that
we
are
submitting
and
referencing
1.
The
TRED
has
a
data
request
for
28
day
Inhalation
study
in
rats.
4.1.1.3
­
`
28­
day
inhalation
toxicity
study
in
the
rat
is
requested
to
better
assess
toxicity
from
inhalation
exposure,
based
on
available
acute
inhalation
data
(
Toxicity
Category
II)
and
the
potential
for
inhalation'.

US
Borax
has
two
more
recent
acute
inhalation
toxicity
limit
studies
on
boric
acid.
In
each
case
the
limit
dose
tested
was
approximately
2
mg/
L
because
of
the
physical
difficulties
in
producing
an
atmosphere
of
boric
acid
dust.
The
second
study
was
carried
out
in
response
to
the
Boric
Acid
RED
at
the
request
of
the
US
EPA
to
confirm
that
the
highest
dose
obtainable
was
2
mg/
l.
It
was
deemed
by
the
US
EPA
to
be
an
acceptable
study.
MRID
no
43500701
and
addendum
submitted
on
August
13,
1996.

Animal
observations
were
limited
due
to
the
accumulation
of
test
material
on
the
walls
of
the
exposure
chamber.
The
LC50
was
>
2.03
mg/
L
from
the
first
study
and
>
2.12.
mg/
L
(
2g/
m3)
from
the
repeat
study.
During
the
first
1.5
hours
of
exposure,
ocular
and
nasal
discharge,
hypoactivity
and
haunched
posture
were
noted.
Ocular
discharge
and
or
nasal
discharge
persisted
in
most
animals
after
removal
from
the
chamber.
All
animals
recovered
by
day
two
after
removal
from
chamber.
A
Robust
Summary
of
the
Second
study
is
Attached.

This
data
indicates
that
the
acute
inhalation
toxicity
should
be
in
Toxicity
Category
III.
In
addition
there
is
no
indication
that
sub
acute
exposure
would
lead
to
adverse
effects.
Therefore
there
should
be
no
need
for
a
28
day
inhalation
study.

References
MRID
53400701,
Wnorowski,
G.
Acute
inhalation
toxicity
limit
on
boric
acid
MG
Test
Product
Safety
Labs,
US,
East
Brunswick,
New
Jersey
08816,
Study
­
5257.
Unpublished
report
to
U.
S.
Borax.
1997
plus
Robust
summary
Robust
Summary
Acute
Toxcity
Inhalation
Boric
Acid
.
doc
Wnorowski,
G.,
(
199a),
Acute
inhalation
toxicity
limit
test
on
boric
acid.
Product
Safety
Labs,
US,
East
Brunswick,
New
Jersey,
0881;
Study
­
3311.
Unpublished
report
to
U.
S.
Borax.
Boric
Acid
/
Sodium
Salts
TRED
 
Comments
December
22,
2005
Page
5
of
9
2.
We
also
note
that
the
critical
NOAEL
is
deemed
to
be
8.8mg
B/
kg
based
on
the
dog
studies
and
based
on
an
overall
assessment
of
all
the
dog
studies.
The
commonly
accepted
NOAEL
for
boron
is
9.6
mg
B/
kg/
day
as
indicated
by
the
list
of
Risk
Assessments
below.
However,
even
if
the
dog
studies
were
used,
it
should
be
refined/
upgraded
to
reflect
the
actual
intakes
of
the
dogs,
based
on
the
actual
dietary
intake
data
rather
than
a
standard
calculated
intake.
This
would
compensate
for
an
error
in
the
dog
study
conclusions
and
indicate
that
the
NOAEL
is
9.6­
10.9
mg
B/
kg,
which
is
in
the
same
range
as
that
for
the
rat
studies.
Many
other
expert
groups
have
determined
that
the
dog
studies,
while
adding
to
the
weight
of
evidence,
are
not
suitable
for
setting
an
NOAEL
for
Risk
Assessment
including
the
US
EPA
(
IRIS
2004)
published
(
Culver
et
al,
1994a;
ECETOC,
1995;
European
Commission,
1996;
Murray,
1995;
Culver
and
Hubbard,
1996;
Hubbard
and
Sullivan,
1996,
Hubbard,
1998;
IPCS,
1998;
WHO;
1998;
Moore
et
al.,
1998;
U.
S.
Food
and
Nutrition
Board.
2001;
US
EPA,
2004;
UK
EVM,
2003;
EFSA,
2004).
There
are
a
number
of
issues
with
these
studies
that
are
not
mentioned
in
the
TRED.

 
4.4.2
does
not
mention
the
equivalent
boric
acid
study.
There
is
a
study
on
both
boric
acid
and
Disodium
tetraborate
decahydrate.
A
Robust
Summaries
of
each
study
is
submitted
 
The
mg
B/
kg
equivalent
dose
intakes
are
incorrect
in
various
publications
because
they
are
based
on
the
standard
food
intakes
for
dogs,
however,
the
original
reports
contain
full
details
of
feed
intake
and
the
NOAEL
can
be
readjusted
to
9,6
mg
B/
kg
based
on
Disodium
tetraborate
decahydrate
study
or
10.9
based
on
a
Boric
acid
study.
The
original
studies
can
be
submitted
for
evaluation.
 
The
number
of
dogs
used
was
low,
with
only
four
dogs
per
dose
level;
these
dogs
were
sacrificed
at
three
different
time
intervals,
resulting
in
variable
group
sizes
of
1­
2
males/
group/
sacrifice
interval.
 
In
the
38­
week
study,
there
were
testicular
lesions,
including
testicular
degeneration
in
3
out
of
4
control
dogs,
and
the
fourth
control
dog
had
a
low
sperm
count.
Although
a
compound­
related
effect
is
apparent
at
the
highest
dose,
firm
conclusions
about
the
NOAEL
cannot
be
drawn.
 
There
is
a
large
gap
between
the
NOAEL
and
LOAEL,
and
the
NOAEL
and
LOAEL
were
determined
from
portions
of
the
study
performed
at
different
times.
In
addition,
there
is
evidence
that
the
effect
at
the
LOAEL
may
be
reversible
which
indicates
that
the
LOAEL
may
be
close
to
the
NOAEL.
This
is
consistent
with
findings
in
rats.
 
Lack
of
statistical
analysis
 
Dogs
were
from
unknown
source
and
of
unknown
age
 
Disease
and
dietary
history
of
dogs
is
unknown
 
Previous
exposure
to
drugs,
pesticides,
chemicals
unknown
 
Dogs
sacrificed
at
different
time
intervals
(
12,
24,
27
months;
26,
38,
41
weeks),
sometimes
with
no
concurrent
control
 
The
dog
is
not
the
most
appropriate
species
for
type
of
study
for
reasons
such
as
seasonal
breeding
performance,
inbreeding
factors,
and
insufficient
historical
background
data.
 
Limited
analysis
of
test
material
 
No
testing
to
determine
homogeneity
of
diet
 
Some
dogs
were
housed
in
metabolism
cages
for
part
of
the
study
Boric
Acid
/
Sodium
Salts
TRED
 
Comments
December
22,
2005
Page
6
of
9
 
Some
dogs
were
catheterized;
others
were
not.
 
Background
level
of
boron
in
the
dog
chow
was
never
measured.
 
The
results
indicate
that
the
testes
is
a
key
target
organ
for
borax
toxicity
in
the
dog,
as
it
was
in
rodent
studies.
The
results
do
not
indicate
that
the
dog
is
a
more
sensitive
species
than
rodents.
 
A
series
of
sophisticated
studies
of
the
reproductive
toxicity
of
boric
acid
was
conducted
by
the
U.
S.
National
Toxicology
Program
in
the
1980s
and
1990s
which
give
a
more
accurate
assessment
of
the
NOAEL
IRIS
2004
"
The
authors
reported
that
there
did
not
appear
to
be
any
definitive
test
article
effect
on
any
parameter
examined.
The
study
pathologist
considered
the
histopathological
findings
to
be
"
not
compound­
induced."

"
The
Weir
and
Fisher
(
1972)
study
in
dogs
had
other
limitations
for
RfD
derivation,
including
small
number
of
test
animals
per
dose
group
(
n=
4),
the
use
of
shared
control
animals
in
the
borax
and
boric
acid
studies
so
that
at
most
two
control
animals
were
sacrificed
at
any
time
period,
the
observation
of
testicular
damage
in
three
of
four
control
animals,
and
the
NOAEL
and
LOAEL
taken
from
two
different
studies
of
different
duration.
Also,
the
study
pathologist
considered
the
histopathological
findings
to
be
"
not
compound­
induced."
Based
on
the
small
number
of
animals
and
the
wide
range
of
background
variability
among
the
controls,
these
studies
do
not
appear
to
be
adequate
for
establishment
of
a
defensible
RfD."

We
reiterate,
in
line
with
other
expert
assessments,
that
the
most
appropriate
NOAEL
for
risk
assessment
is
based
on
developmental
effects
in
rats
and
and
is
55
mg
boric
acid/
kg/
day
(
equivalent
to
9.6
mg
B/
kg/
day)
(
MRID
43340101)

References
Dog
Studies
Weir
RJ.
(
1966)
Two­
Year
Dietary
Feeding
­­
Dogs.
Borax
(
Sodium
Tetraborate
Decahydrate).
Final
Report.
Hazleton
Laboratories,
Inc.
Report
TX­
66­
20.
July
8,
1966.
Weir
RJ
(
1967)
38­
Week
Dietary
Feeding
 
Dogs.
Borax
(
Sodium
Tetraborate
Decahydrate).
Final
Report.
Hazleton
Laboratories.
Report
TX­
67­
4.
February
28,
1967.

Weir
RJ.
(
1966)
Two­
Year
Dietary
Feeding
­­
Dogs.
Boric
Acid.
Final
Report.
Hazleton
Laboratories.
Report
TX­
66­
17.
July
8,
1966.
Wei
RJ
(
1967)
38­
Week
Dietary
Feeding
 
Dogs.
Boric
Acid.
Final
Report.
Hazleton
Laboratories.
Report
TX­
67­
3.
February
28,
1967.

Both
studies
were
published
in
summary
form
in
Weir
RJ
and
Fisher
RS.
(
1972)
Toxicological
studies
on
borax
and
boric
acid.
Toxicol
Appl
Pharmacol.
23(
3):
351­
64.

Robust
Summary
Subchronic
2
year
Dogs
Boric
acid.
doc
Robust
Summary
Subchronic
2
year
Dogs
Tetraborates.
doc
Rat
NOAEL
Study
(
MRID
43320101)
Price
C
J,
Marr
M
C
and
Myers
C
B
(
1994).
Determination
of
the
no­
observable­
adverse­
effect­
level
(
NOAEL)
for
developmental
toxicity
in
Sprague­
Dawley
(
CD)
rats
exposed
to
boric
acid
in
feed
on
gestational
days
0­
20,
and
evaluation
of
postnatal
recovery
through
postnatal
day
21.
Report
No.
65C­
5657­
200.
Research
Triangle
Institute,
Research
Triangle
Park,
NC.
Boric
Acid
/
Sodium
Salts
TRED
 
Comments
December
22,
2005
Page
7
of
9
Additional
General
References
Culver
BD,
R.
G.
Smith,
R.
J.
Brotherton,
P.
L.
Strong
and
T.
M.
Gray,
Boron.
in
Patty's
Industrial
Hygiene
and
Toxicology,
4th
Edition,
Volume
2F,
Chapter
42,
G.
D.
Clayton
and
F.
E.
Clayton
eds.,
John
Wiley
&
Sons
Inc.,
New
York,
NY,
pp
4411­
4448
(
1994a)

Culver
BD
and
S
A
Hubbard.
Inorganic
boron
health
effects
in
humans:
An
aid
to
risk
assessment
and
clinical
judgement.
J
Trace
Elements
in
Experimental
Medicine,
9,
175
­
184,
1996
ECETOC
(
European
Centre
for
Ecotoxicology
and
Toxicology
of
Chemicals),
Toxicology
and
reproductive
toxicity
of
some
inorganic
borates
and
risk
assessment
for
man.,
Technical
Report
No.
63
(
1995).

European
Food
Standards
Agency
(
EFSA)
:
Opinion
of
the
Scientific
Panel
on
Dietetic
Products,
Nutrition
and
Allergies
on
a
request
from
the
Commission
related
to
the
Tolerable
Upper
Intake
Level
of
Boron
(
Sodium
Borate
and
Boric
Acid)
,
The
EFSA
Journal
(
2004)
80,
1­
22
(
Request
N
°
EFSA­
Q­
2003­
018)
(
adopted
on
9
July
2004)

European
Commission.
Opinion
of
the
Scientific
Advisory
Committee
concerning
toxicologically
acceptable
parametric
value
for
boron
in
drinking
water.
CSTE/
96/
4/
V,
February
20,
1996.
(
EC
drinking
water
directive
(
98/
83/
EC)

Hubbard
SA
and
F.
M.
Sullivan,
Toxicological
effects
of
inorganic
boron
compounds
in
animals:
A
review
of
the
literature,
J.
Trace
Elements
in
Experimental
Medicine,
9,
165
­
173
(
1996).

Hubbard
SA
,
Comparative
Toxicology
of
Borates.
Biol.
Trace
Element
Res.
66,
343­
357,
1998.

IPCS
(
International
Programme
on
Chemical
Safety).
"
Environmental
Health
Criteria
204,
Boron."
World
Health
Organization,
IPCS
Working
Group,
1998
Moore,
JA
and
an
Expert
Scientific
Committee.
An
assessment
of
boric
acid
and
borax
using
the
IEHR
evaluative
process
for
assessing
human
developmental
and
reproductive
toxicity
of
agents.
Repro.
Toxicol.
11:
123­
160
(
1997)
and
NTIS
Technical
Report
PB96­
156005,
March,
1995.

Murray
FJ,
A
human
health
risk
assessment
of
boron
(
boric
acid
and
disodium
tetraborate
decahydrate)
in
drinking
water,
Regul.
Toxicol.
Pharmacol.
22,
221­
230
(
1995).

UK
EVM
(
Expert
Group
on
Vitamins
and
Minerals),
Safe
Upper
Limits
for
Vitamins
and
Minerals,
May
2003
(
www.
foodstandards.
gov.
uk)

US
EPA.
2004.
Toxicological
review
of
boron
and
compounds
(
CAS
No.
7440­
42­
8)
In
Support
of
Summary
Information
on
the
Integrated
Risk
Information
System
(
IRIS)
June
2004
U.
S.
Environmental
Protection
Agency
Washington,
DC
June
2004,
EPA
635/
04/
052
www.
epa.
gov/
iris
U.
S.
Environmental
Protection
Agency
Washington,
DCU.
S.
Food
and
Nutrition
Board.
2001.
Dietary
Reference
Intakes:
Vitamin
A,
Vitamin
K,
Arsenic,
Boron,
Chromium,
Copper,
Iodine,
Iron,
Manganese,
Molybdenum,
Nickel,
Silicon,
Vanadium,
and
Zinc.,
pp.
13­
1
­
13­
42.
Institute
of
Medicine,
Washington,
D.
C.

WHO,
1998.
Guidelines
for
drinking
water
quality.
2nd
Edition
Addendum
to
Volume
1.
Recommendations
Boron,
pages
4­
6
adn
Addendum
to
Volume
2
Boron
pages
15­
29.
World
Health
Organisation,
Geneva.

3.
Acute
oral
toxicity
in
dogs:
although
these
figures
are
slightly
different
from
our
calculations
based
on
the
original
data
we
do
not
disagree
with
the
Toxicity
Category
III
conclusions.
However
it
may
be
worth
noting
that
the
dogs
all
vomited
and
therefore
there
is
a
limit
to
how
high
you
can
test
in
a
dog.
Boric
Acid
/
Sodium
Salts
TRED
 
Comments
December
22,
2005
Page
8
of
9
4.
Unscheduled
DNA
synthesis
study:
4.1.1.3:
"
The
unscheduled
DNA
synthesis
study
submitted
to
satisfy
the
genotoxicity
study
requirement
for
guideline
OPPTS
870.5550
(
or
84­
4;
"
other"
non
gene
mutation
and
non­
clastogenic
mechanism)
was
considered
unacceptable."
Although
more
data
has
not
specifically
been
requested
we
have
submitted
an
Amendment
to
the
Final
Report
that
gives
the
individual
UDS
data
to
assist
in
re­
evaluating
this
study.
This
should
assist
in
upgrading
the
study
to
an
`
Acceptable'.

Reference
Bakke
J
P
(
1991).
Evaluation
of
the
potential
of
boric
acid
to
induce
unscheduled
DNA
synthesis
in
the
in
vitro
hepatocyte
DNA
repair
assay
using
the
male
F­
344
Rat.
SRI
International,
Study
No.
2389­
V500­
91,
23
August
1991;
plus
Amendment
1
to
the
Original
Report,
May
20,
1992,
Menlo
Park,
CA.
Unpublished
Report
to
US
Borax
Inc.

5.
4.4.8.1
 
Two
year
Dietary
Study
in
Rats.
This
was
a
review
of
a
study
on
borax
(
Disodium
tetraborate
decahydrate).
There
is
also
a
parallel
study
on
boric
acid
using
the
same
control
groups.
Robust
Summaries
of
both
studies
are
attached.
The
reviewers
note
that
there
is
a
discrepancy
in
the
percent
survival
of
the
mid
dose
males
as
presented
in
the
study
report
(
76.9%)
differed
from
calculation
from
the
data
itself
(
64%).
There
is
a
request
for
the
Registrant
to
submit
clarification
as
confirmatory
data.
We
concur
with
the
reviewer
that
the
mid
dose
male
survival
is
64%
(
as
indicated
in
the
Robust
Summary
attached).
In
fact
it
is
64%
for
both
boric
acid
and
borax
dose
groups.
It
should
be
noted
that
this
study
(
as
with
all
of
the
others
from
the
Hazleton
Laboratories
Inc)
were
carried
out
in
the
1960s
prior
to
GLP
therefore
there
would
not
have
been
a
quality
check
on
all
the
calculations.

References
Weir
R
J
(
1966c).
Two­
year
dietary
feeding
study
­
albino
rats.
Boric
acid.
Final
Report.
Hazleton
Laboratories
Inc.,
Falls
Church,
VA,
July
8th,
1966
(
TX­
66­
18)
and
Addendum
to
Final
Report,
April
10,
1967
(
TX­
67­
6)
Unpublished
report
to
US
Borax
Research
Corporation
Weir
R
J
(
1966d).
Two­
year
dietary
feeding
study
 
albino
rats.
Borax
(
Sodium
tetraborate
decahydrate).
Final
Report
(
TX­
66­
21).
Hazleton
Laboratories
Inc.,
Falls
Church,
VA,
July
8th,
1966
and
Addendum
to
Final
Report,
April
10,
1967(
TX­
67­
9).
Unpublished
report
to
US
Borax
Research
Corporation
Robust
Summary
Chronic
rat
Boric
acid.
doc
Robust
Summary
Chronic
Rat
Tetraborates.
doc
Both
studies
were
published
in
summary
form
in
Weir
RJ
and
Fisher
RS.
(
1972)
Toxicological
studies
on
borax
and
boric
acid.
Toxicol
Appl
Pharmacol.
23(
3):
351­
64.

6.
Dermal
absorption
 
it
is
mentioned
that
there
are
limited
data,
however
the
human
data
that
was
referenced
under
IRIS
is
mentioned.
While
this
is
not
an
issue
we
have
submitted
the
original
human
dermal
absorption
study
Reference
Hui,
X,
Wester,
RC
and
Maibach,
HI,
(
1996)
In
Vivo
Percutaneous
Absorption
of
Boric
Acid,
Borax
and
Octaborate
Tetrahydrate
(
DOT)
in
Man.
Unpublished
Report
to
U.
S.
Borax
Inc.,
Study
Number
H832­
11830­
01,
November
12.
Boric
Acid
/
Sodium
Salts
TRED
 
Comments
December
22,
2005
Page
9
of
9
7.
Relevance
NOAEL
for
a
child
risk
assessment.
We
note
that
there
are
some
unacceptable
scenarios
for
exposures
to
children,
which
are
based
on
comparison
with
the
animal
reproductive
toxicity
NOAEL.

We
would
like
to
question
whether
this
NOAEL
is
the
most
appropriate
NOAEL
for
exposure
to
children,
particularly
very
young
infants
under
some
scenarios
especially
where
single
or
few
exposures
are
likely
(
such
as
after
carpet
application).
The
key
effect
in
children
from
oral
intake
appears
to
be
vomiting
and
diarrhoea.
A
NOAEL
for
both
adults
and
children,
based
on
vomiting
and
diarrhoea
of
1g/
day
(
this
puts
an
extra
safety
factor
into
the
child
risk
assessment
when
based
on
mg/
kg)
can
be
set
based
on
the
available
data.
For
children
they
may
in
fact
be
less
sensitive
than
adults
as
their
renal
clearance
is
greater
than
adults,
therefore
this
would
mean
that
an
extra
safety
factor
was
not
needed
for
children
in
this
case.

References
Culver
BD
and
S
A
Hubbard.
Inorganic
boron
health
effects
in
humans:
An
aid
to
risk
assessment
and
clinical
judgement.
J
Trace
Elements
in
Experimental
Medicine,
9,
175
­
184,
1996
Also
various
Internal
Borax
reviews
8.
5.0
Public
Health
Data
We
note
under
section
5.1
Incident
Reports
­
Final
paragraph
that
`
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'.
We
would
be
very
interested
to
learn
more
about
these
cases
as
we
are
not
aware
of
any
such
incidents.

9.
Section
3.2
Nature
of
the
Residue
in
Drinking
Water
 
last
paragraph
related
to
human
daily
boron
intake.
We
would
like
to
point
the
reviewer
to
other,
more
recent,
comprehensive
intake
data
by
Rainey
et
al
(
1999)

Reference
Rainey,
C.
J.,
Nyquist,
L.
A.,
Christensen,
R.
E.,
Strong,
P.
L.,
Culver,
B.
D.,
and
Coughlin,
J.
C.
1999.
Daily
boron
intake
from
the
American
diet.
J.
Am.
Diet
Assoc.
99(
3),
335­
340.
