Document ID: EPA-HQ-OPP-2005-0062-0026
Agency: epa
Document Type: Supporting & Related Material
Title: 
Posted Date: 2006-08-02T04:00Z

UNITED
STATES
ENVIRONMENTAL
PROTECTION
AGENCY
WASHINGTON,
D.
C.
20460
OFFICE
OF
PREVENTION,
PESTICIDES
AND
TOXIC
SUBSTANCES
Date:
June
26,
2006
MEMORANDUM
SUBJECT:
Boric
Acid/
Sodium
Borate
Salts:
HED
Chapter
of
the
Tolerance
Reassessment
Eligibility
Decision
Document
(
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).
Case
#
0024,
DP
Barcode
D320894.

Regulatory
Action:
Tolerance
Reassessment
Progress
and
Interim
Risk
Management
Decision
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,
Branch
Chief
Toxicology
Branch
Health
Effects
Division
(
7509C)

TO:
Laura
Parsons,
PM/
Nathan
Mottl,
CRM
Reregistration
Branch
I
Special
Review
and
Reregistration
Division
(
7505C)
ii
Table
of
Contents
1.0
Executive
Summary
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Page
1
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2.0
Ingredient
Profile
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Page
5
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2.1
Summary
of
Registered
Uses
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Page
7
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2.2
Nomenclature
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Page
8
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2.3
Physical
and
Chemical
Properties
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Page
9
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3.0
Metabolism
Assessment
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Page
11
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3.1
Comparative
Metabolic
Profile
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Page
11
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3.2
Nature
of
the
Residue
in
Foods
and
in
Drinking
Water
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Page
11
of
82
3.3
Environmental
Degradation
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Page
12
of
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4.0
Hazard
Characterization/
Assessment
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Page
13
of
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4.1
Hazard
and
Dose­
Response
Characterization
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Page
13
of
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4.1.1
Database
Summary
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Page
13
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4.1.1.1
Studies
Available
and
Considered
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Page
13
of
82
4.1.1.2.
Mode
of
Action,
Metabolism,
Toxicokinetic
Data
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Page
13
of
82
4.1.1.3
Sufficiency
of
Studies/
Data
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Page
14
of
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4.1.1.4
Toxicological
Effects­
Data
Summary
and
Toxicity
Profile
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Page
14
of
82
4.1.2
Dose­
response
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Page
21
of
82
4.2
FQPA
Hazard
Considerations
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Page
22
of
82
4.2.1
Adequacy
of
the
Toxicity
Data
Base
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Page
22
of
82
4.2.2
Evidence
of
Neurotoxicity
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Page
22
of
82
4.2.3
Developmental
Toxicity
Studies
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Page
23
of
82
4.2.4
Reproductive
Toxicity
Study
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Page
26
of
82
4.2.5
Additional
Information
from
Literature
Sources
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Page
30
of
82
4.2.6
Pre­
and/
or
Postnatal
Toxicity
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Page
30
of
82
4.2.6.1
Determination
of
Susceptibility
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Page
30
of
82
4.2.6.2
Degree
of
Concern
Analysis
and
Residual
Uncertainties
for
Pre
and/
or
Post­
natal
Susceptibility
.
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Page
31
of
82
4.3
Recommendation
for
a
Developmental
Neurotoxicity
Study
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Page
31
of
82
4.3.1
Evidence
that
supports
requiring
a
Developmental
Neurotoxicity
study
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Page
31
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82
4.3.2
Evidence
that
supports
not
requiring
a
Developmental
Neurotoxicity
study
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Page
31
of
82
4.3.3
Rationale
for
the
UF
DB
(
when
a
DNT
is
recommended)
.
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Page
31
of
82
4.4
Hazard
Identification
and
Toxicity
Endpoint
Selection
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Page
31
of
82
4.4.1
Acute
and
Chronic
Reference
Doses
(
aRfD
and
cRfD)
.
.
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Page
32
of
82
4.4.2
Incidental
Oral,
Short­
and
Intermediate­
Term
Exposures
(
All
Populations)
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Page
32
of
82
4.4.3
Dermal
Absorption
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Page
35
of
82
4.4.4
Dermal
Exposure
(
Short,
Intermediate
and
Long
Term)
.
.
Page
35
of
82
iii
4.4.5
Inhalation
Exposure
(
Short,
Intermediate
and
Long
Term)
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Page
35
of
82
4.4.6
Margins
of
Exposure
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Page
36
of
82
4.4.7
Recommendation
for
Aggregate
Exposure
Risk
Assessments
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Page
37
of
82
4.4.8
Classification
of
Carcinogenic
Potential
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Page
37
of
82
4.4.8.1
Two
Year
Dietary
Study
in
the
Rat
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Page
37
of
82
4.4.8.2
Two
year
dietary
study
in
the
mouse
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Page
39
of
82
4.5
Special
FQPA
Safety
Factor
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Page
41
of
82
4.6
Endocrine
disruption
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Page
41
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82
5.0
Public
Health
Data
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Page
42
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5.1
Incident
Reports
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Page
42
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5.2
Other
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Page
44
of
82
6.0
Exposure
Characterization/
Assessment
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Page
45
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6.1
Dietary
Exposure/
Risk
Pathway
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Page
45
of
82
6.2
Water
Exposure/
Risk
Pathway
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Page
45
of
82
6.3.2
Other
(
Spray
Drift,
etc.)
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Page
45
of
82
6.3
Residential
(
Non­
Occupational)
Exposure/
Risk
Pathway
.
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Page
46
of
82
6.3.1
Home
Uses
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Page
46
of
82
6.3.1.1
Residential
Handler
Exposure
Scenarios
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Page
46
of
82
6.3.1.2
Residential
Postapplication
Exposure
Scenarios
­
Swimming
Pool
Incidental
Oral
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Page
50
of
82
6.3.1.3
Residential
Postapplication
Exposure
Scenarios
­
Children
Handto
Mouth
Transfer
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Page
51
of
82
6.3.1.4
Residential
Handler
Exposure­
Inerts
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Page
53
of
82
6.3.1.5
Residential
Risk
Characterization­
Uncertainties
Associated
With
Residential
Postapplication
Exposures
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Page
54
of
82
6.3.2
Other
(
Spray
Drift,
etc.)
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Page
55
of
82
7.0
Aggregate
Risk
Assessments
and
Risk
Characterization
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Page
55
of
82
8.0
Cumulative
Risk
Characterization/
Assessment
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Page
57
of
82
9.0
Occupational
Exposure/
Risk
Pathway
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Page
57
of
82
10.0
Data
Needs
and
Label
Requirements
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Page
57
of
82
10.1
Toxicology
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Page
57
of
82
10.2
Residue
Chemistry
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Page
58
of
82
10.3
Occupational
and
Residential
Exposure
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Page
58
of
82
References:
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Page
58
of
82
Appendices
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Page
66
of
82
Page
1
of
84
1.0
Executive
Summary
Boric
acid
and
its
sodium
salts
(
sodium
tetraborate
decahydrate,
sodium
tetraborate
pentahydrate,
sodium
tetraborate
anhydrous,
disodium
octaborate
tetrahydrate,
disodium
octaborate
anhydrous
and
sodium
metaborate)
are
inorganic
compounds
used
as
insecticides,
acaricides,
herbicides,
algaecides,
fungicides
and
wood
preservatives.
There
are
numerous
types
of
products
for
these
compounds:
product
formulations
include
wettable
or
water­
soluble
powder,
dust,
liquid
concentrate,
paste,
pellet,
bait,
granule,
soluble
concentrate
and
solid.
The
percentage
of
active
ingredient
ranges
from
less
than
1%
(
e.
g.,
agricultural
food/
feed
products)
to
100%
(
e.
g.,
crack/
crevice
treatments).
Multiple
types
of
use
sites
have
registered
uses,
including
agricultural
application
to
numerous
food/
feed
crops,
indoor
residential
areas
including
pet
quarters
and
wood
preservation,
aquatic
nonfood
residential,
indoor
food
handling/
storage
sites
and
non­
food
sites,
outdoor
residential,
forestry,
terrestrial
non­
food
crops,
medical/
veterinary
areas
and
aquatic
non­
food
industrial
(
sewer
systems)
sites.
The
use
sites,
formulation
types,
target
organisms
and
application
methods/
rates
for
each
of
the
above
active
ingredients
of
this
Reregistration
Case
are
discussed
in
greater
detail
in
the
1993
Registration
Eligibility
Decision
(
RED)
Document
for
boric
acid
and
its
sodium
salts
(
US
EPA,
1993).

In
August,
1993,
EPA
established
an
exemption
from
the
requirement
for
a
tolerance
for
residues
of
boric
acid
and
its
sodium
salts
when
used
as
active
ingredients
in
products
applied
to
all
raw
commodities.
In
September,
1993,
a
RED
document
was
issued
for
boric
acid
and
its
sodium
salts
and
a
tolerance
exemption
was
granted
for
its
use
as
an
inert
ingredient
as
a
sequestrant
or
buffering
agent
in
pesticide
formulations.
The
purpose
of
this
Tolerance
Reassessment
Eligibility
Decision
(
TRED)
document
is
to
reassess
the
exemption
from
the
requirement
of
a
tolerance
for
residues
of
this
chemical
when
used
as
an
active
ingredient
and
an
inert
ingredient
in
pesticide
formulations.
Since
the
original
boric
acid
RED
was
issued
in
September
1993,
prior
to
the
development
of
the
Food
Quality
Protection
Act
(
FQPA)
in
August,
1996,
tolerances
also
need
to
be
reassessed
to
meet
the
FQPA
standard.
The
Agency
has
considered
any
new
data
generated
after
the
tolerance
exemption
was
issued,
new
Agency
guidance
or
other
federal
regulations,
as
well
as
previously
available
information
in
this
assessment.

The
toxicology
database
for
boric
acid
is
considered
complete
at
this
time.
Both
boric
acid
and
sodium
tetraborate
decahydrate
show
low
acute
oral,
dermal
and
inhalation
toxicity
(
Toxicity
Category
III
for
oral
and
dermal
routes
and
Category
II
for
the
inhalation
route),
cause
minimal
or
no
primary
dermal
irritation
(
Category
III
or
IV),
and
boric
acid
does
not
cause
eye
irritation.
Sodium
tetraborate
decahydrate
is
corrosive
to
the
eye
(
Toxicity
Category
I)
and
sodium
metaborate
is
moderately
dermally
irritating.
The
major
target
organ
is
the
testes,
with
testicular
atrophy
and
reduction
in
sperm
production
observed
in
multiple
species.
This
effect
results
in
reduced
fertility,
as
demonstrated
in
rat
and
mouse
reproductive
toxicity
studies.
The
female
reproductive
tract
does
not
appear
to
be
as
sensitive
as
males,
but
reduction
in
the
number
of
ovulating
ovaries
and
fertility
in
crossover
mating
protocols
using
treated
females
and
untreated
males
indicate
that
both
sexes
are
susceptible.
Other
treatment­
related
findings
seen
in
the
available
animal
studies
include
body
weight
decreases,
slight
hematological
effects
and
clinical
signs
of
toxicity
at
higher
dose
levels.
Page
2
of
84
The
fetus
is
also
affected
by
exposure
to
boric
acid
or
sodium
borate
salts.
Developmental
toxicity
studies
in
the
rat
show
increased
fetal
susceptibility,
with
effects
on
skeletal
development
and
pup
weight
being
the
most
sensitive
and
observed
at
doses
that
did
not
cause
maternal
toxicity.
Skeletal
abnormalities
and
reduced
fetal
weight
were
also
observed
in
mice
at
maternally
toxic
doses.
At
higher
dose
levels
in
the
rat
and
rabbit,
visceral
abnormalities
of
the
heart
and/
or
great
vessels
were
observed
and
in
the
rat,
enlarged
lateral
ventricles
of
the
brain
were
observed,
with
the
fetal
effects
in
rabbits
observed
at
maternally
toxic
doses.
Reduced
survival
was
also
reported
in
developmental
and
reproductive
toxicity
studies
at
higher
dose
levels,
with
all
species
tested
(
rat,
rabbit,
mouse)
affected.

Boric
acid/
sodium
borate
salts
are
classified
as
"
not
likely
to
be
carcinogenic
to
humans"
under
the
current
(
2005)
Agency
Guidelines
for
Carcinogen
Risk
Assessment.
Long­
term
dietary
studies
in
the
rat
and
the
mouse
did
not
show
evidence
of
treatment­
related
increases
in
tumors
and
the
available
genotoxicity
data
do
not
indicate
mutagenic
potential.

Although
boric
acid/
sodium
borate
salts
are
registered
for
use
on
numerous
food/
feed
crops,
no
dietary
or
drinking
water
risk
assessments
were
performed.
Boron
is
a
naturally
occurring
component
of
both
food
and
water
and
is
believed
to
be
an
essential
dietary
trace
nutrient,
though
a
minimum
daily
requirement
has
not
been
established.
The
contribution
of
boron
residues
from
agricultural
food/
feed
applications
is
expected
to
be
less
than
the
total
dietary
background
intake
of
boron,
based
on
limited
available
residue
data
and
the
relatively
low
application
rate
for
agricultural
uses.
Similarly,
although
these
products
are
expected
to
be
mobile
in
the
soil
and
readily
dissolve
in
water
(
present
as
undissociated
acid),
the
low
application
rate
of
agricultural
products
is
not
expected
to
add
significantly
to
the
background
levels
naturally
occurring
in
drinking
water.

Incident
report
data
indicate
that
although
exposures
to
boric
acid­
related
products
in
general
result
in
fewer
and
less
severe
outcomes
relative
to
other
pesticides,
significant
toxicity
may
occur
from
either
oral
or
inhalation
exposure
with
misuse,
particularly
over­
application.
Common
symptoms
reported
include
vomiting,
eye
irritation,
nausea,
skin
rash,
oral
irritation
and
respiratory
effects.

Exposure
assessments
for
this
tolerance
reassessment
were
performed
for
(
1)
residential
handler
inhalation
exposure
from
application
of
pesticide
products
and
non­
pesticidal
consumer
products
containing
boric
acid
or
borax,
(
2)
postapplication
incidental
oral
ingestion
in
young
children
from
hand­
to­
mouth
transfer
from
carpet
and
crack/
crevice
treatment
products;
(
3)
postapplication
incidental
oral
ingestion
in
young
children
from
pressure­
treated
wood
and
in
situ
deck­
spray
treatments;
and
(
4)
postapplication
incidental
oral
exposure
in
children
and
adults
from
swallowing
treated
swimming
pool
water.

The
following
endpoints
pertinent
to
the
preliminary
risk
assessment
for
this
tolerance
reassessment
were
selected:
Page
3
of
84
°
An
incidental
oral
endpoint
for
all
populations
and
exposure
durations
(
one
day
through
six
months)
was
selected
from
dog
subchronic
and
chronic
dietary
toxicity
studies
in
the
rat,
based
on
testicular
atrophy
and
slight
hematological
changes;

°
An
inhalation
endpoint
for
all
populations
and
exposure
durations
(
one
day
through
long­
term
or
lifetime)
for
residential
handler
exposure
(
adults)
was
selected
from
subchronic
and
chronic
dietary
toxicity
studies
in
the
dog,
based
on
testicular
atrophy
and
slight
decreases
in
hematocrit/
hemoglobin;

°
Dermal
exposure
scenarios
for
residential
handlers
were
not
included
in
this
assessment
because
boric
acid
and
it
sodium
salts
are
not
well
absorbed
across
intact
skin
and
are
not
anticipated
to
be
a
significant
source
of
internal
dosing.

An
uncertainty
factor
(
UF)
of
100
(
using
the
default
values
of
10
for
interspecies
extrapolation
and
10
for
intraspecies
variation)
was
selected;
a
Margin
of
Exposure
(
MOE)
of
100
is
required
for
all
residential
exposure
risk
assessment
scenarios.
The
Food
Quality
Protection
Act
(
FQPA)
safety
factor
was
reduced
to
1X:
although
increased
sensitivity
of
fetuses
was
observed,
based
on
decreased
fetal
weight
and
skeletal
effects
in
the
rat
developmental
toxicity
studies,
the
database
of
four
developmental
toxicity
studies
in
three
species,
plus
two
reproductive
toxicity
studies
in
two
species,
is
considered
sufficient
to
characterize
hazard
and
no
residual
uncertainties
remain.
The
endpoint
selected
for
risk
assessment
(
testicular
atrophy)
is
comparable
to
the
most
sensitive
developmental
endpoint.
In
addition,
the
UF
of
100
is
considered
a
conservative
value
because
boric
acid/
sodium
salts
are
not
metabolized,
thereby
reducing
the
intra­
and
interspecies
variability
from
individual
variations
in
metabolic
enzyme
activities,
and
because
pharmacokinetics
(
absorption,
tissue
distribution,
lack
of
significant
soft
tissue
retention)
in
humans
and
other
species
are
expected
to
be
somewhat
similar.
The
endpoint
was
used
for
exposure
scenarios
for
children,
in
addition
to
adults,
because
there
is
at
present
insufficient
information
to
rule
out
the
possibility
that
boron
may
cause
toxicity
to
the
immature
reproductive
system
of
either
males
or
females.
It
was
used
for
all
exposure
durations
due
to
uncertainty
of
the
time
to
onset
of
this
effect.
The
endpoint
did
not
include
the
background
dietary
boron
consumption;
actual
total
boron
consumption
per
day
would
therefore
be
higher
but
this
information
was
not
provided
in
the
study.
Individuals
with
impaired
renal
clearance
are
anticipated
to
be
a
more
sensitive
subpopulation.

The
results
of
the
exposure
assessments
are
as
follows:

°
The
residential
handler
inhalation
risks
due
to
boric
acid
and
its
sodium
salts
as
active
ingredients
are
not
a
risk
concern
and
do
not
exceed
the
level
of
concern
(
LOC)
of
100
(
handler
inhalation
MOEs
range
from
800
to
5,600,000).
Residential
inhalation
exposure
to
non­
pesticidal
consumer
products
also
do
not
exceed
the
LOC
of
100
(
MOEs
range
from
16,000
to
13,000,000).

°
MOEs
for
postapplication
exposure
scenarios
for
hand
to
mouth
transfer
in
children
from
indoor
surfaces
(
carpet
treated
with
dust
or
spray)
do
not
exceed
the
LOC
of
100
(
MOEs
$
170).

°
MOEs
for
postapplication
exposure
scenarios
for
hand
to
mouth
transfer
in
Page
4
of
84
children
from
pressure­
treated
wood
or
in
situ
deck
spray
treatment
do
not
exceed
the
LOC
of
100
(
MOEs
$
180).

°
For
incidental
oral
exposure
from
ingestion
of
swimming
pool
water,
the
MOEs
for
adults
and
children
older
than
age
10
exposed
to
sodium
tetraborate
pentahydrate
at
water
concentrations
of
240
mg/
L,
and
for
children
(
all
ages)
and
adults
exposed
to
boric
acid,
did
not
exceed
the
LOC
of
100
(
MOE
range
110
to
5,600)
and
are
not
a
risk
concern.
However,
the
MOEs
for
children
age
7
to
10
from
incidental
oral
exposure
from
swimming
pool
water
treated
with
sodium
tetraborate
pentahydrate
are
of
concern,
with
MOEs
of
65
to
74
at
pool
water
concentrations
of
480
and
240
mg/
L,
respectively.

°
The
use
of
products
containing
boric
acid
and
its
sodium
salts
as
inert
ingredients
was
also
examined,
however,
many
of
the
scenarios
were
already
examined
in
terms
of
products
containing
these
chemicals
as
active
ingredients.
For
those
active
ingredient
scenarios,
the
MOEs
were
greater
than
the
target
MOE
of
100
and
it
was
assumed
that
the
inert
use
products,
containing
a
smaller
percentage
of
the
chemicals,
would
also
pose
no
risk.
Certain
postapplication
scenarios
with
active
ingredient
uses
resulted
in
MOEs
less
than
100
and
these
were
reexamined
for
the
inert
use
products.
All
of
the
resulting
MOEs
were
greater
than
the
target
MOE
of
100
and
are
not
a
risk
concern.

An
aggregate
exposure
risk
assessment
was
not
conducted
for
boric
acid/
sodium
borate
salts
to
characterize
the
risk
from
dietary
intake
(
food
and
drinking
water)
plus
residential
uses,
including
exposure
from
pesticidal,
inert
and
consumer
uses.
No
tolerances
or
residue
data
are
available
to
perform
a
dietary
exposure
assessment.
The
limited
available
residue
data
(
citrus,
cottonseed),
upon
which
tolerance
exemptions
were
based,
suggests
that
pesticide
residues
from
boric
acid/
sodium
borate
salt
agricultural
applications
do
not
significantly
contribute
to
the
total
dietary
intake
of
boron.
For
residential
uses
of
pesticidal
products,
the
risks
for
incidental
oral
exposure
to
children
from
swallowing
treated
swimming
pool
water
at
two
of
three
label­
directed
concentrations
exceed
the
level
of
concern
and
fill
the
risk
cup.
Therefore,
although
the
MOEs
for
residential
handlers/
applicators
were
not
of
concern
($
800
for
inhalation
exposure;
dermal
not
conducted
because
dermal
absorption
is
negligible),
an
aggregate
exposure
is
not
conducted
when
risks
(
in
this
case,
from
postapplication
exposures
to
children)
exceed
the
level
of
concern.
However,
it
is
noted
that
the
lowest
swimming
pool
water
concentration
treatment
does
not
show
MOEs
that
exceed
the
level
of
concern.
The
Agency
also
considered
exposures
from
nonpesticidal
sources
of
boron
(
consumer
products
such
as
laundry
detergent
or
general
purpose
cleaners,
and
pesticidal
products
containing
boric
acid
or
sodium
borate
salts
as
inerts).
Based
on
the
large
MOEs
for
handler/
applicator
inhalation
exposure
to
the
consumer
products
(
MOEs
$
16,000)
and
postapplication
incidental
oral
exposure
to
children
or
adults
from
swallowing
pool
water
treated
with
pesticidal
products
containing
boric
acid
as
an
inert
(
MOEs
$
5,600),
these
exposure
scenarios
would
not
be
a
significant
source
of
boron
internal
dosing
and
would
not
contribute
significantly
to
total
daily
boron
exposure
when
compared
to
the
diet.
Page
5
of
84
A
cumulative
risk
assessment
has
not
been
performed
for
boric
acid
and
sodium
borate
salts
because
at
this
time
there
are
no
known
compounds
with
which
they
share
a
common
mechanism
of
toxicity.

Additional
data
are
required
for
boric
acid/
sodium
borate
salts.
In
order
to
confirm
the
values
used
for
the
postapplication
exposure
assessments
for
wood
treatment
uses,
crack
and
crevice
application
and
carpet
dust,
data
in
support
of
these
assessments
is
required.
Page
6
of
84
2.0
Ingredient
Profile
Boric
acid
and
sodium
salts
of
boric
acid
are
inorganic
pesticides
acting
as
acaricides,
algaecides,
fungicides,
herbicides
and
insecticides
and
are
used
on
a
variety
of
agricultural
(
including
food/
feed),
non­
agricultural,
residential,
commercial,
medical,
industrial
and
food/
feed
handling
sites.
These
compounds
act
as
acaricides
and
insecticides
either
as
a
stomach
poison
or
by
abrasion
of
exoskeletons.
When
used
as
an
herbicide
or
algaecide,
they
act
by
causing
dessication
or
interruption
of
photosynthesis.
Products
classified
as
fungicides
are
wood
preservatives.

Many
different
formulations
are
registered
for
products
containing
boric
acid
or
its
sodium
salts,
including
liquids,
soluble
and
emulsifiable
concentrates,
granulars,
powders,
dusts,
pellets,
tablets,
solids,
paste,
baits
and
crystalline
rods.
The
percentage
of
active
ingredients
in
these
products
may
range
from
less
than
1%
to
99­
100%.
Boric
acid
and
sodium
salts
may
also
be
used
as
inerts
in
the
formulations
of
other
pesticide
products.
Page
7
of
84
Table
2.1
Tolerance
Exemptions
Being
Reassessed
in
this
Document
Tolerance
Exemption
Expression
CAS
Nos.
40
CFR
PC
Code
Use
Pattern
List
Classification
Boric
Acid
and
its
Sodium
Salts
Active
ingredient
Boric
Acid:
10043­
35­
3
11113­
50­
1
41685­
84­
1
180.1121
011001
Acaricide,
algaecide,
fungicide,
herbicide,
insecticide
NA
Sodium
tetraborate
decahydrate:
1303­
96­
4
12447­
40­
4
011102
Fungicide,
insecticide,
herbicide
Sodium
tetraborate
pentahydrate:
11130­
12­
04
12178­
04­
3
011110
Algaecide,
herbicide,
insecticide
Sodium
tetraborate
anhydrous:
1330­
43­
4
12007­
42­
0
011112
Acaricide,
herbicide,
insecticide
Disodium
octaborate
tetrahydrate:
12008­
41­
2
12280­
03­
4
011103
Fungicide,
insecticide
Disodium
octaborate
anhydrous:
12008­
41­
2
12280­
03­
4
011107
Fungicide
Sodium
metaborate:
15293­
77­
3
7775­
19­
1
011104
Herbicide
Inert
Ingredient
Boric
Acid:
10043­
35­
3
11113­
50­
1
41685­
84­
1
180.920a
Used
in
pesticide
formulations
applied
to
growing
crops;
formulation
applied
to
swimming
pools;
and
general
purpose
cleaners
NA
Sodium
tetraborate:
1330­
43­
4
12007­
42­
0
Sodium
metaborate:
15293­
77­
3
7775­
19­
1
a
Residues
listed
in
section
(
d)
of
40
CFR
180.920
are
exempt
from
a
tolerance
when
used
in
accordance
with
good
agricultural
practice
as
inert
ingredients
in
pesticide
formulations
applied
to
growing
crops
only.
Page
8
of
84
2.1
Summary
of
Registered
Uses
Agricultural
food/
feed
crops
for
which
sodium
tetraborate
decahydrate
is
registered
are
listed
below:

Alfalfa
Celery
Lettuce,
leaf
Potato,
white
Almond
Cherry
Melons
Pumpkin
Apple
Cotton
Nectarine
Raspberry
Apricot
Cucumber
Onion
Spinach
Beans
(
dried)
Eggplant
Peach
Squash
(
all)
Beans
(
succulent)
Garbanzos
Peanuts
(
unspec.)
Strawberry
Blackberry
Garlic
Peas,
southern
Sugar
beet
Blueberry
Grapes
Peas,
succulent
Tomato
Broccoli
Grass
forage/
hay
Pecan
Walnut
Cabbage
Hops
Pepper
Bermudagrass
Carrots
Lentils
Pistachio
Cauliflower
Lettuce,
head
Plum
Application
rates
for
these
crops
range
from
0.01637
to
0.06574
lb/
A.
All
applications
are
foliar
via
spray
(
sprayer)
or
low
volume
spray
(
concentrate)(
low
volume
ground
sprayer).
Application
by
aircraft
or
irrigation
is
not
permitted.
The
minimum
retreatment
interval
is
7
days
and
the
reentry
interval
is
12
hours
for
all
crop
applications.
Additional
maximal
seasonal
rates
and
applications
are
not
specified
on
the
label.
Other
use
limitations
may
apply.

Other
non­
agricultural
food/
feed
uses
include
baits,
traps,
dusts,
liquids,
powders,
sprays,
rods,
etc.
for
control
of
insects
such
as
ants
or
roaches
by
application
in
eating
establishments,
food
processing
plant
premises
(
non­
food
contact),
premises
where
food
is
sold,
marketed,
stored
or
distributed,
households
and
poultry
houses
(
egg/
meat).

Nonfood/
nonfeed
residential
uses
pertinent
to
this
tolerance
reassessment
(
incidental
oral
exposure
to
children
and
adults;
inhalation
exposure
to
adults
from
household
residential
application)
include
products
for
residential
carpet
treatment,
crack/
crevice
treatment
and
swimming
pool
algae
control.
Additional
details
on
these
applications
may
be
found
in
the
Residential
(
Non­
Occupational)
Exposure/
Risk
Pathway
section
(
Section
6.3)
of
this
document.

There
are
also
numerous
other
commercial,
industrial,
medical/
veterinary
and
agricultural
non­
food/
feed
use
sites
for
boric
acid
and
its
sodium
salts.
These
include
animal
housing,
turf,
wood
(
preservative),
forests,
sewage
systems,
commercial
storage/
transportation,
medical/
veterinary
institutions,
uncultivated
agricultural/
nonagricultural
areas,
refuse/
solid
waste
sites
and
ornamental
lawns
and
turf,
paved
areas
and
aquatic
structures.

Boric
acid,
sodium
metaborate,
and
sodium
tetraborate
are
identified
as
inert
ingredients
as
a
sequestrant,
buffering
agent/
corrosion
inhibitor,
and
sequestrant,
respectively.
CFR
180.920
allows
these
inert
ingredients
in
pesticide
formulations
applied
to
growing
crops
only
to
be
exempt
from
the
requirement
for
a
tolerance.
Page
9
of
84
2.2
Nomenclature
Nomenclature
for
boric
acid
and
its
sodium
salts
are
presented
below
in
Tables
2.2a
through
2.2g
(
see
Table
2.3
for
boric
acid
structure).

TABLE
2.2a.
Boric
Acid
Nomenclature
Empirical
Formula
H3BO3
Common
name
boric
acid
Other
names
orthoboric
acid,
boracid
acid
PC
Number
011001
CAS
Registry
Number
10043­
35­
3
TABLE
2.2b.
Sodium
Tetraborate
Decahydrate
Nomenclature
Empirical
Formula
Na2B4O7
.
10H20
Common
name
sodium
tetraborate
decahydrate
Other
names
borax
decahydrate,
borax
10
mol,
disodium
tetraborate
decahydrate,
sodium
borate
decahydrate,
sodium
pyroborate
10H20
PC
Number
011102
CAS
Registry
Number
1303­
96­
4
TABLE
2.2c.
Sodium
Tetraborate
Pentahydrate
Nomenclature
Empirical
Formula
Na2B4O7
.
5H20
Common
name
sodium
tetraborate
pentahydrate
Other
names
disodium
tetraborate
pentahydrate,
borax
pentahydrate,
sodium
borate
pentahydrate,
sodium
biborate
5H20,
sodium
pyroborate
5H20
PC
Number
011110
CAS
Registry
Number
11130­
12­
4
or
12179­
04­
3
TABLE
2.2d.
Sodium
Tetraborate
Anhydrous
Nomenclature
Empirical
Formula
Na2B4O7
Common
name
sodium
tetraborate,
anhydrous
Other
names
borax
(
anhydrous),
sodium
borate
(
anhydrous),
sodium
biborate
(
anhydrous),
sodium
pyroborate
(
anhydrous)

PC
Number
011112
CAS
Registry
Number
1330­
43­
4
Page
10
of
84
TABLE
2.2e.
Disodium
Octaborate
Tetrahydrate
Nomenclature
Empirical
Formula
Na2B8O13
.
4H20
Common
name
disodium
octaborate
(
anhydrous)

Other
names
­­

PC
Number
011107
CAS
Registry
Number
12008­
41­
2
TABLE
2.2f.
Disodium
Octaborate
Anhydrous
Nomenclature
Empirical
Formula
Na2B8O13
.
4H20
Common
name
disodium
octaborate
(
anhydrous)

Other
names
­­

PC
Number
011103
CAS
Registry
Number
12008­
41­
2
TABLE
2.2g.
Sodium
Metaborate
Nomenclature
Empirical
Formula
NaBO2
Common
name
Sodium
metaborate
Other
names
­­

PC
Number
011104
CAS
Registry
Number
15293­
77­
3
2.3
Physical
and
Chemical
Properties
The
physical
and
chemical
properties
of
boric
acid
and
its
sodium
salts
are
provided
in
Table
2.3.
There
are
no
known
impurities
of
concern
in
any
of
these
boron
compounds.
With
the
exception
of
sodium
metaborate,
which
will
absorb
carbon
dioxide
to
form
sodium
carbonate
and
borax,
these
compounds
are
stable
under
storage
at
room
temperature.
Page
11
of
84
Table
2.3
Physical/
Chemical
Properties
of
Boric
acid
and
its
Sodium
Salts
Chemical
Molecular
formula
Molecular
weight
Physical
state
Meltin
g
point
Solubility
in
water
pH
Density/
Specific
Gravity
Vapor
Pressure
Estimated
Octanol/
Water
Coefficient
Boric
Acid
H3BO3
61.9
Solid
crystalline
powder
171oC
5.6
g/
100mL
5.1
(
1%
solution
at
20oC)
1.51
at
20oC
<
10­
4
torr
at
200C
0.175
Sodium
tetraborate
decahydrate
Na2B4O7
.

10H20
381.87
crystalline
powder
75oC
4.70
g/
100
mL
at
20oC
9.2
(
1%
solution
at
20oC)
1.73
<
10­
6
torr
0.175
Sodium
tetraborate
pentahydrate
Na2B4O7
.

5H20
291.35
mild
white
alkaline
salt
<
200oC
3.59%
at
20oC
9.2
(
1%
solution
at
20oC)
1.82
<
10­
6
torr
No
data
Sodium
tetraborate
Na2B4O7
201.27
Solid
crystalline
or
amorphous
742oC
2.56
g/
100
mL
at
20oC
No
data
2.37
<
10­
6
torr
No
data
Disodium
octaborate
tetrahydrate
Na2B8O13
.

4H20
412.31
Powder
815oC
9.5%
at
20oC
8.5
(
1%
solution
at
23oC)
25­
35
lbs/
ft3
(
specific
gravity)
<
10­
6
torr
No
data
Disodium
octaborate
Na2B8O13
340.31
Solid
rods
No
data
No
data
No
data
1.8
g/
mL
at
20oC
<
10­
6
torr
No
data
Sodium
metaborate
NaBO2
65.82
Solid
white
pieces
or
powder
Fuses
to
clear
glass
at
966oC
Soluble
in
water
11.82
(
6%
aqueous
solution
of
tetrahydrate
Bulk
density:
loose
pack
(
51­
55
lbs/
ft3)
and
tight
pack
(
55­
61
lbs/
ft3)
<
10­
6
torr
No
data
References:
EPA,
1993;
NIOSH,
2001.
Page
12
of
84
3.0
Metabolism
Assessment
3.1
Comparative
Metabolic
Profile
Boric
acid
and
borate
salts
exist
as
the
undissociated
acid
in
aqueous
solution
at
physiological
pH.
No
further
metabolism
occurs
in
either
animals
or
plants.
The
compounds
are
therefore
considered
to
be
toxicologically
similar
and
comparisons
can
be
made
based
on
boron
equivalents
(
percentages
used
for
conversion
to
boron
equivalents
are
shown
below
in
Table
3.1).
In
animals,
boric
acid/
borate
salts
are
essentially
completely
absorbed
following
oral
ingestion.
Absorption
occurs
via
inhalation,
although
quantitative
data
are
unavailable.
Limited
data
indicate
that
boric
acid/
salts
are
not
absorbed
through
intact
skin
to
any
significant
extent,
although
absorption
occurs
through
skin
that
is
severely
abraded.
It
distributes
throughout
the
body
and
is
not
retained
in
tissues,
except
for
bone,
and
is
rapidly
excreted
in
the
urine
(
US
EPA
IRIS,
2004).

Table
3.1.
Boron
Equivalents
Chemical
Percent
boron
Boric
acid
17.5%

Sodium
tetraborate
decahydrate
11.34%

Sodium
tetraborate
pentahydrate
14.85%

Sodium
tetraborate
21.49%

Disodium
octaborate
tetrahydrate
20.96%

Disodium
octaborate
25.38%

3.2
Nature
of
the
Residue
in
Foods
and
in
Drinking
Water
Boron
exists
naturally
in
plants
and
is
present
in
edible
crops.
The
diet
is
a
major
source
of
natural
background
exposure
to
humans.
Dietary
intake
of
boron
also
results
from
naturally
occurring
amounts
in
drinking
water.

The
natural
concentration
of
boron
in
plants
varies
considerably
among
different
crops
and
variations
are
also
seen
in
reported
levels
for
a
given
crop.
Levels
tend
to
be
highest
in
fruits
(
especially
dried
fruits),
nuts
and
pulses.
For
example,
analyses
of
foods
from
the
United
States
has
given
levels
of
boron
in
peanut
butter
of
about
15
ppm,
avocados
about
11
ppm,
prunes
about
22
ppm,
grapes
about
5
ppm
and
bananas
have
levels
around
1
ppm;
some
analyses
of
foods
conducted
in
other
countries
showed
even
higher
levels
(
Anderson
et
al.,
1994;
Naghii
et
al.,
1996).
Agricultural
application
rates
of
boric
acid
or
borate
salt
products
are
very
low
and
available
residue
data
on
cottonseed
and
citrus
(
revoked
tolerances
of
30
and
8
ppm,
respectively)
indicate
low
residue
levels
as
well,
compared
to
the
naturally
occurring
food
crop
boron
levels.
For
lemons
(
not
currently
a
registered
use),
1
ppm
incremental
boron
was
observed
due
to
treatment,
compared
with
an
endogenous
level
of
2.5
ppm.
The
contribution
of
these
residues
to
total
background
dietary
boron
intake
was
considered
to
be
relatively
small.
A
tolerance
exemption
was
therefore
granted
for
boric
acid
and
its
sodium
salts
(
CFR
180.1121).
Page
13
of
84
Analyses
of
boron
levels
in
fresh
(
surface
water
and
public
water
systems)
and
sea
water
have
been
published
(
summarized
in
EPA
IRIS,
2004
and
ATSDR,
1992).
Concentrations
of
boron
in
fresh
water
vary,
depending
upon
environmental
conditions
and
local
soil
levels,
but
concentrations
in
fresh
water
normally
range
from
<
0.01
to
1.5
ppm
(
average
of
0.1
ppm)
but
may
be
higher
in
areas
of
very
high
soil
boron
levels.
A
survey
of
989
public
water
supply
systems
in
the
United
States
showed
that
90%
had
concentrations
of
0.4
ppm
or
less
and
99%
had
concentrations
less
than
1
ppm.
On
average,
sea
water
contains
higher
boron
concentrations
(
range
0.5
to
9.6
ppm;
average
4.6
ppm).

Estimates
of
human
daily
dietary
boron
intake
(
food
plus
drinking
water)
in
the
United
States
range
from
0.26
to
7.1
mg/
day
with
a
mean
of
1.9
mg/
day
(
equivalent
to
about
0.03
mg/
kg/
day
for
adults;
Moore,
1997).
Other
survey
data
indicate
average
daily
dietary
boron
intakes
of
0.5
to
3.1
mg/
day
(
0.007
to
0.044
mg/
kg/
day)(
Nielsen,
1991).
The
FDA
determined
an
average
U.
S.
adult
male
dietary
boron
intake
of
1.52
mg/
day
(
0.025
mg/
kg/
day)(
Iyengar
et
al.,
1988).

Rainey
et
al.
(
1999)
also
estimated
daily
boron
intake
in
the
diet
using
a
boron
nutrient
database
from
the
US
Department
of
Agriculture
and
individual
food
consumption
patterns.
Populations
included
school­
age
children,
adult
males
and
females
(
non­
vegetarian
and
vegetarian)
and
pregnant
females.
Values
were
presented
as
mean,
5th
to
95th
percentile
and
high
values.
Adult
males
ranged
from
0.43
to
2.42
mg/
day,
with
a
high
of
9.64
and
mean
of
1.17
mg/
day
(
about
0.017
mg/
kg/
day).
Adult
females
ranged
from
0.33
to
1.94
mg/
day
with
a
high
of
8.5
mg/
day
and
a
mean
of
0.96
mg/
day
(
approximately
0.016
mg/
kg/
day).
Values
for
pregnant
females
were
slightly
higher.
Intakes
of
vegetarian
males
and
females
were
on
average
20­
27%
above
non­
vegetarians
and
boron
intakes
in
females
in
the
95th
percentile
were
about
twice
those
of
95th
percentile
nonvegetarians,
but
high
values
were
lower
than
non­
vegetarians.
School­
age
children
showed
a
range
of
0.32
to
1.95
mg/
day
and
high
of
3.83
mg/
day,
with
means
of
approximately
0.90
mg/
day
for
all
age
ranges
(
approximately
0.016
to
0.03
mg/
kg/
day
for
older
and
younger
children,
respectively).

3.3
Environmental
Degradation
Boron
exists
in
nature
chemically
bound
to
oxygen,
either
as
boric
acid
or
as
alkali
or
alkaline
earth
borates,
and
is
present
in
water
and
soil.
It
is
not
transformed
or
degraded
in
the
environment,
although
the
exact
form
may
change
depending
upon
physical
conditions
such
as
moisture
or
pH.
In
nature,
it
enters
water
and
soil
largely
through
weathering.
The
environmental
fate
of
boric
acid
and
its
sodium
salts
from
agricultural
applications
is
the
same
as
for
naturally
occurring
boron
compounds.
Page
14
of
84
4.0
Hazard
Characterization/
Assessment
4.1
Hazard
and
Dose­
Response
Characterization
4.1.1
Database
Summary
4.1.1.1
Studies
Available
and
Considered
Acute­
LD50
(
oral,
dermal
and
inhalation),
rat;
primary
dermal
irritation,
primary
eye
irritation;
Subchronic­
oral
toxicity,
rat
(
2);
oral
toxicity,
dog;
Chronic
and/
or
carcinogenicity­
oral
toxicity,
rat
(
2­
year
dietary);
oral
carcinogenicity,
mouse
(
2­
year
dietary),
oral
chronic
dog
(
2
year
dietary
and
38­
week
dietary);
Reproductive/
developmental­
oral
developmental
toxicity,
rat
(
2);
oral
developmental
toxicity,
rabbit;
oral
developmental
toxicity,
mouse;
oral
multigeneration
reproductive
toxicity,
rat;
oral
multigeneration
reproductive
toxicity,
mouse;
Other­
genotoxicity
screening
studies,
all
categories.

4.1.1.2.
Mode
of
Action,
Metabolism,
Toxicokinetic
Data
Boric
acid
and
its
sodium
salts
exist
as
undissociated
boric
acid
in
aqueous
solution
at
physiological
pH.
For
this
reason,
they
are
considered
together
as
a
group
for
purposes
of
hazard
and
risk
characterization
and
individual
toxicology
studies
on
each
active
ingredient
are
not
required.
The
moiety
of
toxicological
concern
is
boron.
Dose
comparisons
are
normalized
by
conversion
to
boron
equivalents,
allowing
comparison
of
studies
on
boric
acid
or
borax
(
see
Table
3.1).
They
are
well­
absorbed
via
the
gastrointestinal
tract
and
via
inhalation,
but
not
via
intact
skin.
Absorption
across
severely
abraded
skin
does
occur.
Boric
acid/
borates
distribute
evenly
throughout
the
body
and
do
not
bioaccumulate
in
soft
tissues,
but
some
accumulation
may
occur
in
bone.
Excretion
is
rapid
and
primarily
urinary.
Metabolism
of
boric
acid
and
its
salts
does
not
occur
in
vivo,
but
it
may
bind
and
form
complexes
with
some
macromolecules.

Limited
mode
of
action
data
are
available
for
boric
acid/
borate
salts.
The
primary
mechanistic
investigations
published
in
the
literature
to­
date
are
on
testicular
toxicity
(
decreased
spermiation
and
testicular
atrophy)
and
developmental
effects
to
the
skeleton.
In
the
testes,
the
mechanism
of
toxicity
is
unknown,
but
it
is
suspected
that
boron
affects
the
Sertoli
cells,
resulting
in
alterations
in
the
control
of
sperm
maturation
and
release.
Data
indicate
that
boron
causes
a
slight
reduction
in
plasma
testosterone
in
rats
and
that
the
inhibition
of
spermiation
may
be
CNSmediated
as
suggested
by
a
lack
of
direct
effect
on
steroidogenesis
in
Leydig
cells
in
in
vitro
studies
(
Ku
and
Chapin,
1994).
Co­
cultures
of
Sertoli
cells/
germ
cells
in
these
studies
indicate
in
vitro
effects
on
DNA
synthesis
of
mitotic/
meiotic
germ
cells
and
on
Sertoli
cell
energy
metabolism.
However,
additional
data
are
needed
to
characterize
the
mechanism
of
toxicity
of
boron
to
the
testes.
Page
15
of
84
The
exact
mechanisms
causing
skeletal
abnormalities
and
growth
retardation
in
the
developing
fetus
are
also
not
definitively
identified.
There
are
some
data
in
the
rat
to
suggest
that
boron
may
alter
expression
of
the
hox
gene,
a
homeotic
gene
regulating
vertebral
and
rib
development,
an
effect
that
may
occur
after
a
single
maternal
exposure
(
Narotsky
et
al.,
2003;
Wery
et
al.,
2003).
However,
this
effect
was
only
examined
at
a
high
dose
level
(
500
mg/
kg,
twice
daily)
and
there
are
no
studies
examining
dose­
response
at
doses
relevant
to
human
exposure.
Other
data
suggest
effects
of
boron
on
ribs
by
binding
to
bone
tissue
and
a
reduction
of
fetal
growth
by
a
general
inhibition
of
mitosis
(
Fail
et
al.,
1998).

4.1.1.3
Sufficiency
of
Studies/
Data
The
toxicology
database
for
boric
acid
and
its
sodium
salts
is
considered
complete
at
this
time.
No
additional
toxicology
studies
are
required
to
support
this
tolerance
reassessment.

It
is
noted
that
a
number
of
the
studies
used
to
evaluate
boric
acid/
borates
were
conducted
prior
to
current
Agency
study
conduct
guidelines
and
do
not
meet
current
standards,
but
that
when
taken
together,
they
are
considered
adequate
to
provide
a
hazard
characterization.
The
same
studies
have
been
used
for
boron
hazard
characterizations
by
several
other
reviewing
groups
and
Agencies
(
for
example,
WHO,
ATSDR,
US
EPA
IRIS,
ECETOC).

4.1.1.4
Toxicological
Effects­
Data
Summary
and
Toxicity
Profile
The
database
for
acute
toxicity
for
boric
acid
and
sodium
tetraborate
decahydrate
(
borax)
is
shown
below
in
Tables
4.1a
and
4.1b.
Boric
acid
and
borate
salts
have
low
toxicity
by
the
oral
and
dermal
route
(
Toxicity
Category
III)
and
are
not
dermal
irritants
(
Toxicity
Category
III
or
IV),
except
for
sodium
metaborate,
which
is
moderately
irritating
to
the
skin.
In
addition
to
rats,
acute
oral
studies
were
conducted
in
dogs
but
vomiting
was
noted
shortly
after
dosing,
indicating
a
limited
ability
to
test
in
this
species.
Boric
acid
is
classified
as
Toxicity
Category
II
by
the
inhalation
route
but
only
a
single
dose
was
tested
and
an
LC
50
was
not
determined.
Although
boric
acid
is
not
very
irritating
to
the
eyes
(
Toxicity
Category
III),
sodium
tetraborate
decahydrate
(
borax)
is
corrosive
(
Toxicity
Category
I).
Human
lethal
doses
for
oral
ingestion
have
been
estimated
from
accidental
poisonings:
in
adults,
the
minimum
lethal
oral
dose
is
estimated
at
15­
20
g,
in
children
at
5­
6
g
and
in
infants
2­
3
g
(
Stokinger,
1981;
Litovitz,
1988;
see
also
Section
5.0,
Public
Health
Data).
Page
16
of
84
Table
4.1a
Acute
Toxicity
Profile
­
Boric
Acid
Guideline
No.
Study
Type
MRID(
s)
Results
Toxicity
Category
870.1100
Acute
oral
rat
00006719
LD50
males
=
3450
mg/
kg
(
2950­
4040
mg/
kg)
females
=
4080
mg/
kg
(
3640­
4560
mg/
kg)
III
870.1100
Acute
oral
beagle
dog
00064208
LD50
>
631
mg/
kg
III
870.1200
Acute
dermal
rabbit
00106011
LD50
>
2
g/
kg
III
870.1300
Acute
inhalation
rat
00005592
LC50>
0.16
mg/
L
(
no
deaths)
II
870.2400
Acute
eye
irritation
rabbit
00064209
Conjunctival
irritation
clearing
by
Day
4
III
870.2500
Acute
dermal
irritation
rabbit
00106011
PIS
=
0.1;
1/
6
erythema
at
72
hrs
III
870.2600
Skin
sensitization
guinea
pig
­­
Not
required
­­

Table
4.1b
Acute
Toxicity
Profile
­
Sodium
tetraborate
decahydrate
(
Borax)

Guideline
No.
Study
Type
MRID(
s)
Results
Toxicity
Category
870.1100
Acute
oral
rat
40692303
LD50
males
=
4550
mg/
kg
(
4140­
5010
mg/
kg);
females
=
4980
mg/
kg
(
4310­
5760
mg/
kg)
III
870.1100
Acute
oral
dog
40692304
LD50
>
974
mg/
kg
III
870.1200
Acute
dermal
rabbit
43553201
LD50
>
2000
mg/
kg
III
870.1300
Acute
inhalation
rat
­­
Not
required
­­

870.2400
Acute
eye
irritation
rabbit
43553203
Corrosive
I
870.2500
Acute
dermal
irritation
rabbit
43553202
Non­
irritating
IV
870.2600
Skin
sensitization
­­
Not
required
­­

The
subchronic,
chronic
and
other
guideline
studies
submitted
to
support
registration
of
boric
acid
and
its
sodium
salts
are
summarized
below
in
Table
4.1c.

Boron
is
a
ubiquitous
element
that
is
naturally
occurring
in
plants
and
water.
Humans
ingest
boron
in
the
diet
and
there
is
some
data
to
suggest
that
trace
levels
are
required.
This
has
not
been
proven
at
this
time
and
the
FDA
has
not
determined
a
minimum
daily
requirement
(
MDR)
for
boron.
At
higher
exposure
levels,
boron
causes
toxicity.
A
major
target
organ
of
Page
17
of
84
boric
acid/
borate
salts
is
the
testes
and
males
appear
somewhat
more
sensitive
to
boric
acid/
borate
salts
than
females.
The
mechanism
for
testicular
atrophy
is
not
known
at
this
time,
but
seminiferous
tubule
degeneration,
atrophy,
reduction
in
sperm
count
and
reduced
testicular
weights
are
observed
across
species.
Dogs
appear
to
be
more
sensitive
to
this
effect
than
rats
or
mice.
The
ovaries
are
also
a
target
organ
and
a
reduction
in
the
number
of
corpora
lutea
were
observed
in
female
rats
in
a
reproductive
toxicity
study.
Crossover
matings
in
rat
reproductive
toxicity
studies
demonstrate
that
fertility
is
lower
in
both
treated
males
and
females,
but
the
effect
on
fertility
in
females
is
considerably
less
severe
than
in
males.
The
red
blood
cell
may
be
a
potential
target
at
higher
dose
levels,
based
on
slight
hematological
changes
reported
in
some
studies
in
the
rat
and
the
dog.

The
developing
fetus
is
also
sensitive
to
boric
acid
and
its
sodium
salts
at
doses
that
do
not
produce
direct
maternal
toxicity
(
e.
g.,
maternal
reductions
in
gravid
weight
or
weight
gains
are
secondary
to
fetal
toxicity).
Effects
on
the
fetus
include
skeletal
variations/
malformations,
visceral
malformations,
increased
mortality
and
reduced
pup
weight.
Visceral
fetal
abnormalities
were
also
reported:
enlarged
lateral
ventricles
of
the
brain
were
observed
in
the
rat
and
defects
of
the
great
vessels
and
the
heart
were
observed
in
the
rabbit.

Clinical
signs
of
neurotoxicity
have
been
reported
at
higher
dose
levels.
Seizures,
convulsions,
headaches,
tremors
and
in
some
cases,
coma
and
death
have
been
observed
in
human
infants
accidentally
poisoned
by
boric
acid
or
borax
in
medical
case
reports.
In
the
guideline
studies
submitted
to
the
Agency
for
review,
significant
clinical
signs
of
toxicity
were
observed
in
the
rat
at
higher
dose
levels;
symptoms
included
hunched
posture,
rapid
respiration
and
abnormal
gait.
Other
symptoms
included
swollen
paws
and
penis,
ocular
inflammation,
bloody
nasal
discharge
and
coarse
fur/
desquamation.

Under
the
current
Agency
Cancer
Guidelines
(
US
EPA,
2005),
boric
acid/
sodium
salts
are
classified
as
"
not
likely
to
be
carcinogenic
to
humans."
Tumor
incidence
did
not
show
a
clear
treatment­
related
increase
in
mice
or
rats
administered
boric
acid
or
sodium
tetraborate
decahydrate
for
two
years.
Mutagenicity
studies
in
several
test
systems
are
negative.
Epidemiological
data
do
not
indicate
any
exposure­
related
cancers
in
humans
(
US
EPA
IRIS,
2004).
Page
18
of
84
Table
4.1c
Subchronic,
Chronic
and
Other
Toxicity
Profiles
for
Boric
Acid
and
Borate
Salts
Guideline
No./
Study
Type
MRID
No.
(
year)/
Classification
/
Doses
Results
(
Note:
all
dose
levels
for
NOAELs
and
LOAELS
in
this
table
are
expressed
as
mg/
kg/
day
of
boron
equivalents)

870.3100
90­
Day
oral
toxicity
(
rat)
00068025
(
1962)
Acceptable/
nonguideline
together
with
00068883
0,
0.03,
0.1,
0.3,
1.0
or
3.0%
boric
acid
in
diet
for
90
days.
Equivalent
to
0,
3.9,
13,
38,
124
or
500
mg/
kg/
day
boron
NOAEL
=
38
mg/
kg/
day
LOAEL
=
124
mg/
kg/
day,
based
on
clinical
signs
of
toxicity,
decreased
body
weight,
testicular
atrophy/
reduced
testicular
weights,
reduced
ovarian
weights.

870.3100
90­
Day
oral
toxicity
(
rat)
40692305
(
1963)
Acceptable/
nonguideline
together
with
40692306
0,
0.0463,
0.154,
0.463,
1.54
or
4.63%
sodium
tetraborate
decahydrate
in
diet
for
90
days.
Equivalent
to
0,
4.0,
14,
42,
125
or
455
mg/
kg/
day
boron
NOAEL
=
42
mg/
kg/
day
LOAEL
=
125
mg/
kg/
day
based
on
decr.
weight
gain
and
food
consumption,
decr.
testes
and
ovarian
weights,
testicular
atrophy.

870.3100
90­
Day
oral
toxicity
(
rat,
male
rat
only)
40692306
(
1963)
Acceptable/
nonguideline
together
w/
40692305
0,
0.015,
0.0463,
0.154
or
0.463%
sodium
tetraborate
decahydrate
in
diet
for
90
days.
Equivalent
to
0,
1.3,
4.3,
13.1
or
41
mg/
g/
day
boron
NOAEL
=
41mg/
kg/
day
(
males
only
tested)
LOAEL
>
41
mg/
kg/
day
(
HDT).

870.3150
90­
Day
oral
toxicity
(
dog)
00064203
(
1963)
Acceptable/
nonguideline
together
with
40692308
and
00005622
0,
0.01,
0.1
or
1.0%
boric
acid
in
diet
for
90
days.
Equivalent
to
0,
0.46,
4.2
or
35
mg/
kg/
day
boron
NOAEL
=
4.2
mg/
kg/
day
LOAEL
=
35
mg/
kg/
day,
based
on
testicular
atrophy
870.3150
90­
Day
oral
toxicity
(
dog)
40692307
(
1963)
Acceptable/
nonguideline
0,
0.0154,
0.154,
1.54%
sodium
tetraborate
decahydrate
in
diet
for
90
days.
Equivalent
to
0,
0.34/
0.25,
4.1/
2.6
or
32/
23
[
M/
F]
mg/
kg/
day
boron
NOAEL
=
4.1mg/
kg/
day
M/
2.6
mg/
kg/
day
F
LOAEL
=
32
mg/
kg/
day
M/
23
mg/
kg/
day
F,
based
on
decr.
HCT/
Hgb,
testicular
atrophy,
decr.
testes
weight
and
incr.
hemosiderin
pigment
in
spleen,
liver,
kidneys.
Table
4.1c
Subchronic,
Chronic
and
Other
Toxicity
Profiles
for
Boric
Acid
and
Borate
Salts
Guideline
No./
Study
Type
MRID
No.
(
year)/
Classification
/
Doses
Results
(
Note:
all
dose
levels
for
NOAELs
and
LOAELS
in
this
table
are
expressed
as
mg/
kg/
day
of
boron
equivalents)

Page
19
of
84
870.3700a
Prenatal
developmental
(
rat)
41725401
(
1990)
Acceptable/
nonguideline
0,
0.1,
0.2,
0.4%
GD
0­
20
and
0.8%
GD
6­
15
boric
acid
in
diet.
equivalent
to
0,
14,
29
or
58
mg/
kg/
day
boron
and
94
mg/
kg/
day
boron
Maternal
NOAEL
=
58
mg/
kg/
day
Developmental
NOAEL
<
14
mg/
kg/
day
LOAEL
=
14
mg/
kg/
day
based
on
slightly
decr.
fetal
body
weight.
At
29
mg/
kg/
day,
skeletal
abnormalities
observed
and
at
58
and
94
mg/
kg/
day,
high
incidence
skeletal
and
visceral
abnormalities,
and
mortality
870.3700a
Prenatal
developmental
(
rat)
43340101
(
1994)
Acceptable/
nonguideline
0,
0.025%,
0.050%,
0.075%,
0.10%
or
0.20%
boric
acid.
Equivalent
to
0,
3.3,
6.3,
9.6,
13.3
or
25
mg/
kg/
day
boron
Maternal
NOAEL
=
25
mg/
kg/
day
LOAEL
=
not
determined
(
slightly
decreased
gravid
uterine
weight
considered
secondary
to
fetal
toxicity)
Developmental
NOAEL
=
9.6
mg/
kg/
day
LOAEL
=
13.3
mg/
kg/
day
based
on
slightly
decr.
fetal
body
weight,
rib
XIII
abnormalities
870.3700a
Prenatal
developmental
(
mouse)
41725402
(
1990)
Acceptable/
nonguideline
0,
0.1,
0.2,
0.4%
boric
acid
in
diet
equivalent
to
0,
43,
79
or
176
mg/
kg/
day
boron
Maternal
NOAEL
not
established
<
43
mg/
kg/
day
LOAEL
=
43
mg/
kg/
day
based
on
renal
tubular
dilatation/
regeneration.
Developmental
NOAEL
=
43
mg/
kg/
day
LOAEL
=
79
mg/
kg/
day
based
on
decr.
fetal
wt,
incr.
resorptions,
incr.
malformations
(
short
rib
XIII,
fused
rib).

870.3700b
Prenatal
developmental
(
rabbit)
42164201,
42164202
(
1991)
Acceptable/
guideline
0,
62.5,
125
or
250
mg/
kg/
day
boric
acid
by
gavage.
Equivalent
to
0,
11,
22
or
44
mg/
kg/
day
boron
Maternal
NOAEL
=
22
mg/
kg/
day
LOAEL
=
44
mg/
kg/
day
based
on
incr.
intrauterine
bleeding,
decreased
unadjusted
weight
gain
during
treatment
(
due
to
decr.
gravid
uterine
weight).
Developmental
NOAEL
=
22
mg/
kg/
day
LOAEL
=
44
mg/
kg/
day
based
on
incr.
mortality
(
resorptions,
postimplantation
loss),
decr.
fetal
weight,
intraventricular
septal
defect,
enlarged
aorta.

870.3800
Reproduction
and
fertility
effects
(
rat)
00068882
(
1966)
Acceptable/
nonguideline
0,
0.067,
0.20
or
0.67%
boric
acid
in
the
diet.
Equivalent
to
0,
8.5/
9.7,
27/
29
or
85/
92
mg/
kg/
day
[
M/
F]
boron
Parental/
Systemic
NOAEL
=
27
mg/
kg/
day
LOAEL
=
85
mg/
kg/
day
based
on
clinical
signs,
decr.
body
weight,
testicular
atrophy,
decr.
testes
weight,
decr.
corpora
lutea.
Reproductive
NOAEL
=
27
mg/
kg/
day
LOAEL
=
85
mg/
kg/
day
based
on
decr.
fertility.
Offspring
NOAEL
=
27
mg/
kg/
day
LOAEL
=
85
mg/
kg/
day
based
on
decr.
pup
survival.
Table
4.1c
Subchronic,
Chronic
and
Other
Toxicity
Profiles
for
Boric
Acid
and
Borate
Salts
Guideline
No./
Study
Type
MRID
No.
(
year)/
Classification
/
Doses
Results
(
Note:
all
dose
levels
for
NOAELs
and
LOAELS
in
this
table
are
expressed
as
mg/
kg/
day
of
boron
equivalents)

Page
20
of
84
870.3800
Reproduction
and
fertility
effects
(
rat)
40692311(
1966)
Acceptable/
nonguideline
0,
0.103,
0.308
or
1.03%
sodium
tetraborate
decahydrate
in
the
diet.
Equivalent
to
0,
8.1/
9.2,
25/
27
or
82/
92
[
M/
F]
mg/
kg/
day
boron
Parental/
Systemic
NOAEL
=
25
mg/
kg/
day
LOAEL
=
82
mg/
kg/
day
based
on
decr.
body
weight,
testicular
atrophy,
decr.
testes
weight,
decr.
corpora
lutea.
Reproductive
NOAEL
=
25
mg/
kg/
day
LOAEL
=
82
mg/
kg/
day
based
on
decr.
fertility.
Offspring
NOAEL
=
25
mg/
kg/
day
LOAEL
=
82
mg/
kg/
day
based
on
decr.
pup
survival.

870.3800
Reproduction
and
fertility
effects
(
mouse)
41589101
(
1990)
Acceptable/
nonguideline
0,
1000,
4500
or
9000
ppm
boric
acid
in
diet
(
for
P1
matings
only
0
and
1000
ppm
groups).
Equivalent
to
0,
27,
111
or
221
mg/
kg/
day
boron
Parental/
Systemic
NOAEL
=
27
mg/
kg/
day
LOAEL
=
111
mg/
kg/
day
based
on
decr.
testicular
weight,
atrophy
and
degeneration
of
seminiferous
tubules.
Reproductive
NOAEL
=
27
mg/
kg/
day
LOAEL
=
111
mg/
kg/
day
based
on
decr.
fertility.
Offspring
NOAEL
=
27
mg/
kg/
day
LOAEL
=
111
mg/
kg/
day
based
on
decr.
pup
wt.,
decreased
survival
870.4100a
Chronic
toxicity
(
rat)
see
870.4200,
below
870.4100b
Chronic
toxicity
(
dog)
00005624
(
1967)
Acceptable/
nonguideline
when
considered
together
with
00005622
and
4366910.
0
or
0.67%
boric
acid
decahydrate
in
diet
for
38
weeks.
Equivalent
to
0
or
40
mg/
kg/
day
boron
NOAEL
not
established
($
40
mg/
kg/
day)
LOAEL
=
40
mg/
kg/
day,
based
on
testicular
atrophy,

870.4100b
Chronic
toxicity
(
dog)
40692308
(
1967)
Acceptable/
nonguideline
when
considered
together
with
40692307,
­
09.
0
or
1.03%
sodium
tetraborate
decahydrate
in
diet
for
38
weeks.
Equivalent
to
0
or
40
mg/
kg/
day
boron
NOAEL
not
established
(<
40
mg/
kg/
day)
LOAEL
=
40
mg/
kg/
day
based
on
decr.
body
wt.
gain,
testicular
atrophy.
Table
4.1c
Subchronic,
Chronic
and
Other
Toxicity
Profiles
for
Boric
Acid
and
Borate
Salts
Guideline
No./
Study
Type
MRID
No.
(
year)/
Classification
/
Doses
Results
(
Note:
all
dose
levels
for
NOAELs
and
LOAELS
in
this
table
are
expressed
as
mg/
kg/
day
of
boron
equivalents)

Page
21
of
84
870.4100b
Chronic
toxicity
(
dog)
00005622
(
1966)
Acceptable/
nonguideline
when
considered
together
with
00005624
and
00064203
0,
0.033,
0.067
or
0.20%
boric
acid
in
diet
for
two
years.
Equivalent
to
0,
1.6,
3.6
or
10.2
mg/
kg/
day
boron,
males
and
0,
1.8,
4.0
or
11.6
mg/
kg/
day
boron,
females
NOAEL
=
10.2
mg/
kg/
day
LOAEL
not
established
($
10.2
mg/
kg/
day)

870.4100b
Chronic
toxicity
(
dog)
40692310
(
1967)
Acceptable/
nonguideline
when
considered
together
with
40692308.
0,
0.051,
0.103
or
0.309%
sodium
tetraborate
decahydrate
in
the
diet
for
two
years
.
Equivalent
to
0,
1.5,
2.9
or
8.8
mg/
kg/
day
boron
NOAEL
=
8.8
mg/
kg/
day
LOAEL
not
established
(>
8.8
mg/
kg/
day)

870.4200
Carcinogenicity
(
rat)
00068883
(
1966)
Acceptable/
nonguideline
0,
0.01,
0.1
or
1.0%
boric
acid
in
the
diet
for
two
years.
Equivalent
to
0,
5.2,
16
or
58
mg/
kg/
day
boron,
males;
0,
6.3,
19
or
70
mg/
kg/
day
boron,
females
NOAEL
=
16
mg/
kg/
day
LOAEL
=
58
mg/
kg/
day,
based
on
clinical
signs,
decreased
body
weight,
decreased
testicular
weight,
testicular
atrophy,
increased
anovulatory/
involuted
ovaries,
decreases
in
RBC
parameters.
no
evidence
of
carcinogenicity
870.4200
Carcinogenicity
(
rat)
40692309
(
1966)
Acceptable/
nonguideline
0,
0.130,
0.308,
1.030%
sodium
tetraborate
decahydrate
in
diet
for
two
years.
Equivalent
to
0,
7.3,
17
or
58
mg/
kg/
day
boron
NOAEL
=
17
mg/
kg/
day
LOAEL
=
58
mg/
kg/
day
based
on
decr.
body
weight
(
observed
by
3­
4
weeks),
testicular
atrophy,
slightly
decreased
hematocrit/
hemoglobin.
no
evidence
of
carcinogenicity
870.4300
Carcinogenicity
(
mouse)
41861301
(
1991)
Acceptable/
nonguideline
0,
2500
or
5000
ppm
boric
acid.
Equivalent
to
0,
78
or
201
mg/
kg/
day
boron
NOAEL
=
not
established
<
78
mg/
kg/
day
LOAEL
=
201
mg/
kg/
day
based
on
splenic
lymphoid
depletion
in
males
and
pulmonary
hemorrhage.
Decr.
body
weights
in
males
and
females;
testicular
atrophy,
interstitial
cell
atrophy
at
5000
ppm
(
201
mg/
kg/
day).
no
evidence
of
carcinogenicity
Table
4.1c
Subchronic,
Chronic
and
Other
Toxicity
Profiles
for
Boric
Acid
and
Borate
Salts
Guideline
No./
Study
Type
MRID
No.
(
year)/
Classification
/
Doses
Results
(
Note:
all
dose
levels
for
NOAELs
and
LOAELS
in
this
table
are
expressed
as
mg/
kg/
day
of
boron
equivalents)

Page
22
of
84
Gene
Mutation
870.
Mouse
in
vitro
lymphoma
forward
gene
mutation
assay
42038902
(
1991)
Acceptable/
guideline
1200­
5000
µ
g/
mL
boric
acid
+/­
S9
Negative
for
induction
of
mutagenic
response
in
two
independently
performed
mouse
L5178Y
cell
lymphoma
forward
mutation
assays.
Marginal
cytotoxicity
at
3500­
5000
µ
g/
mL.

Gene
Mutation
870.
S.
typhimurium
reverse
gene
mutation
assay
42038901
(
1991)
Acceptable/
guideline
10­
2500
µ
g/
plate
boric
acid
Negative
for
induction
of
mutagenic
response
in
S.
typhimurium
strains
TA1535,
TA1537,
TA1538,
TA98
or
TA100
in
the
presence
or
absence
of
S9
up
to
2500
µ
g/
plate.
No
cytotoxicity
was
observed.

Cytogenetics
870.
Mouse
in
vivo
micronucleus
assay
42038904
(
1991)
Acceptable/
guideline
900,
1800
or
3500
mg/
kg
boric
acid
Negative
for
induction
of
clastogenic
response
to
the
bone
marrow
of
Swiss
mice.
No
systemic
toxicity
or
target
cytotoxicity
observed
up
to
3500
mg/
kg.

Other
Effects
870.
Rat
liver
in
vitro
unscheduled
DNA
synthesis
42038903
(
1991)
Acceptable/
guideline
5­
5000
µ
g/
mL
boric
acid
Negative
for
increased
unscheduled
DNA
synthesis
in
cultured
rat
hepatocytes.
Slightly
increased
percent
cells
in
repair
at
$
2500
µ
g/
mL
in
repeat
assay
were
secondary
to
increased
cytotoxicity
at
those
dose
levels.

4.1.2
Dose­
response
Appropriate
endpoints
protective
for
the
most
sensitive
effects
were
identified
for
all
potential
exposure
scenarios
for
boric
acid
and
its
sodium
salts.
The
primary
effects
of
concern
for
the
endpoints
selected
were
testicular
atrophy
and
developmental
toxicity,
including
skeletal
abnormalities
and
decreased
fetal
body
weight.

This
risk
assessment
was
conducted
for
a
tolerance
reassessment
for
boric
acid
and
sodium
borate
salt
products,
which
includes
residential
uses
as
well
as
food/
feed
uses.
However,
boric
acid
and
sodium
salts
are
exempt
from
tolerances
due
to
low
levels
of
residues
relative
to
endogenous
levels
of
boron
found
in
food/
feed
crops
and
drinking
water,
and
lack
of
significant
retention
in
animal
products.
Acute
and
chronic
dietary
exposure
assessments
were
not
conducted
as
part
of
this
reassessment
because
of
the
minor
contribution
to
total
dietary
boron
intake
anticipated
from
crop
residues.
Background
dietary
intake
was
not
included
in
the
risk
assessment
because
it
was
assumed
that
the
test
animals
from
the
studies
evaluated
to
derive
endpoints
ingested
background
levels
of
boron
in
food
and
drinking
water
that
would
approximate
an
average
intake
by
humans.

Incidental
oral
postapplication
exposure
is
anticipated
to
occur
to
children
and
adults
from
swallowing
treated
swimming
pool
water.
Various
household
uses
including
carpet
treatment
and
other
residential
scenarios
would
also
result
in
postapplication
incidental
oral
exposure
to
young
Page
23
of
84
children
from
hand­
to­
mouth
ingestion.
The
endpoint
selected
for
exposure
to
both
children
and
adults
is
testicular
atrophy
in
the
dog
for
short
and
intermediate­
term
exposure
durations.
This
endpoint
was
used
for
children
under
twelve
because
at
present
it
is
not
known
if
the
mechanism
of
testicular
toxicity
is
also
relevant
to
the
immature
testes
or
testicular
development
(
or
to
the
developing
female
reproductive
system).

Boric
acid/
sodium
borate
salts
are
not
absorbed
across
intact
skin,
based
on
the
available
data.
Dermal
exposure
is
not
expected
to
be
of
concern
and
no
endpoints
were
selected
for
residential
dermal
exposure
risk
assessment.

Since
there
are
no
inhalation
studies
for
boric
acid
and
its
sodium
salts,
oral
studies
were
selected
for
inhalation
risk
assessment.
The
systemic
toxicity
NOAEL
from
the
dog
two­
year
dietary
study
and
LOAEL
from
the
dog
subchronic
dietary
study
were
combined
and
used
to
select
an
endpoint
that
was
protective
for
testicular
atrophy
at
all
exposure
durations.

A
quantification
of
cancer
risk
is
not
required
since
boric
acid/
borate
salts
are
classified
as
"
not
likely
to
be
carcinogenic
to
humans"
under
the
current
(
2005)
Agency
Guidelines
for
Carcinogen
Risk
Assessment.

For
all
exposure
scenarios,
uncertainty
factors
of
10x
for
interspecies
and
10x
for
intraspecies
variation
(
total
UF
of
100x)
were
used.
However,
this
is
considered
a
conservative
UF
because
boric
acid/
sodium
salts
are
expected
to
show
similar
absorption
and
tissue
distribution
among
different
species.
There
is
also
no
known
metabolism
of
boric
acid/
sodium
salts
that
could
cause
variability
among
species
or
individuals
due
to
differing
levels
of
metabolic
enzymes.

4.2
FQPA
Hazard
Considerations
4.2.1
Adequacy
of
the
Toxicity
Data
Base
The
toxicology
database
for
boric
acid
and
borate
salts
is
considered
adequate
for
assessment
of
FQPA
hazard
considerations
at
this
time.
Several
developmental
toxicity
and
reproductive
toxicity
studies
in
multiple
species
are
available
for
evaluation.
Effects
have
also
been
characterized
in
standard
subchronic
and
chronic
dietary
studies
in
several
species.

4.2.2
Evidence
of
Neurotoxicity
Rat
neurobehavioral
screening
studies
on
boric
acid/
borate
salts
have
not
been
conducted
and
are
not
a
requirement
for
reregistration.
The
available
experimental
and
case
report
data
indicate
the
potential
for
neurotoxicity
at
higher
exposure
levels
(
see
Section
5.0,
Public
Health
Data).
Case
reports
in
humans
indicate
that
neurological
symptoms
may
occur
at
higher
exposure
levels.
Reports
of
infant
accidental
poisonings
note
CNS
symptoms
such
as
convulsions,
headaches,
tremors
and
restlessness.
Degenerative
changes
in
brain
neurons,
congestion
and
brain
edema
and
meninges
were
reported
in
infants
that
died
of
boron
poisoning,
although
it
is
not
Page
24
of
84
known
whether
these
changes
represent
primary
neurotoxicity
or
are
secondary
to
acute
systemic
toxicity.
Other
symptoms
of
boron
poisoning
reported
in
human
case
studies
and
incident
reports
include
lethargy,
headache,
vomiting,
abdominal
pain
and
diarrhea.

Possible
neurobehavioral
symptoms
were
reported
in
the
rat
in
subchronic
and
chronic
dietary
studies
submitted
to
the
Agency
but
only
at
high
dose
levels.
Symptoms
included
hunched
posture,
abnormal
gait
and
rapid
respiration,
although
it
is
noted
that
these
occurred
in
the
presence
of
numerous
other
symptoms
(
swollen
paws
and
penis,
inflamed
eyes,
bloody
nasal
discharge,
emaciation,
coarse
fur/
desquamation
and
shrunken
scrotum)
and
could
also
have
been
secondary
to
systemic
effects.
In
one
of
the
rat
developmental
toxicity
studies,
enlarged
lateral
ventricles
of
the
brain
of
fetuses
was
observed
at
a
maternally
toxic
dose
level.
The
dose
at
which
this
was
reported
(
58
mg/
kg/
day)
was
significantly
higher
than
the
lowest
NOAEL
for
developmental
toxicity
(
9.6
mg/
kg/
day),
with
the
effect
also
not
observed
in
the
rat
at
14
or
29
mg/
kg/
day.

4.2.3
Developmental
Toxicity
Studies
(
1)
Rat:
In
a
developmental
toxicity
study
(
MRIDs
41725401,
main
report
and
42377101,
supplement),
29
pregnant
Crl
CD(
BR)
VAF/
Plus
outbred
Sprague­
Dawley
rats/
dose
group
were
administered
boric
acid
(
technical,
98­
99%
a.
i.)
in
the
diet
at
concentrations
of
0,
0.1,
0.2
or
0.4%
(
equivalent
to
an
average
daily
dose
of
0,
78,
163
or
330
mg/
kg/
day
boric
acid
and
0,
14,
29
or
58
mg/
kg/
day
of
boron
equivalents)
from
gestation
days
0
through
20
(
dosing
schedule
designed
to
allow
plasma
boron
levels
to
reach
steady
state
prior
to
implantation
to
mimic
low­
dose
exposure
from
food).
Additional
control
and
high
dose
groups
of
14
pregnant
rats
each
were
administered
the
test
diet
at
0%
or
0.8%
from
gestation
days
6
through
15
(
equivalent
to
an
average
daily
dose
of
539
mg/
kg/
day
boric
acid
and
94
mg/
kg/
day
boron
equivalents).

Maternal
toxicity:
At
0.2%,
statistically
significantly
increased
relative
kidney
weight
(
right
and
left)
was
observed
(
about
+
10%
above
controls),
with
a
similar
but
nonsignificant
increase
in
absolute
right
and
left
kidney
weight;
relative
liver
weight
was
also
increased
(+
5%,
p<
0.05);
however,
these
marginal
changes
were
not
considered
to
be
adverse.
At
0.4%,
a
statistically
significant
reduction
in
body
weight
gain
(­
10%
below
controls)
and
gravid
uterine
weight
(­
30%
below
controls)
were
observed.
Statistically
significantly
increased
left
kidney
weight
(+
8%;
right
similar
increase
but
not
significant)
was
also
seen.
At
0.8%,
(
treatment
only
GD
6­
15),
mean
body
weight
gain
and
gravid
uterine
weight
during
treatment
were
about
­
58
to
­
59%
lower
than
controls.
No
treatment­
related
effects
on
survival
or
clinical
signs
were
reported.
The
maternal
toxicity
NOAEL
is
0.4%
(
330
mg/
kg/
day
boric
acid;
58
mg/
kg/
day
boron
equivalents).
A
LOAEL
was
not
determined
in
this
study.

Developmental
toxicity:
At
0.1%,
mean
fetal
body
weight
was
marginally
but
statistically
significantly
reduced
(­
6%
less
than
controls);
this
was
considered
a
threshold
effect.
At
0.2%,
decreased
mean
fetal
weight
(­
13%
below
controls),
and
increased
incidences
of
the
litter
incidence
of
short
rib
XIII
(
28%
vs
1%,
controls),
and
cleft
sternum
(
4%
vs
0%,
controls)
were
Page
25
of
84
reported.
At
0.4%,
increased
fetal
resorptions,
rib
XIII
agenesis
(
24
fetuses
vs.
0
in
controls),
enlarged
lateral
ventricles
in
the
brain
(
21
vs.
0
fetuses
in
controls;
fetal
incidence
0.5%)
were
observed
(
fetal
weight
­
37%
below
controls).
At
the
high
dose
of
0.8%,
prenatal
mortality
(
live
fetuses
per
litter
mean
9.71
vs.
15.39­
15.69
in
other
groups)
was
observed.
Numerous
gross
malformations
(
short
and
curly
tail,
anophthalmia,
microphthalmia),
visceral
malformations
(
cardiovascular
defects,
convoluted
retina,
enlarged
lateral
ventricles)
were
observed
along
with
rib
XIII
agenesis,
short
rib
XIII
and
cleft
sternum.
At
0.4%
and
0.8%,
100%
of
the
litters
were
affected
with
skeletal
malformations
or
other
defects;
visceral
malformations
were
reported
in
36%
and
86%
of
litters,
respectively.
The
developmental
toxicity
LOAEL
(
threshold
effect
level)
is
0.1%
(
78
mg/
kg/
day
boric
acid;
14
mg/
kg/
day
boron
equivalents),
based
on
marginally
decreased
fetal
weight
and
increased
incidence
of
skeletal
variations.
A
developmental
toxicity
NOAEL
was
not
determined
in
this
study.

The
developmental
toxicity
study
in
the
rat
is
classified
acceptable
(
nonguideline)
and
satisfies
the
guideline
requirement
for
a
developmental
toxicity
study
(
OPPTS
870.3700;
OECD
414)
in
the
rat.
The
test
material
was
administered
via
the
diet
instead
of
gavage
to
mimic
human
dietary
exposure.

(
2)
Rat:
In
an
oral
developmental
toxicity
study
(
MRID
43340101),
boric
acid
(
technical,
99%
a.
i.)
was
administered
to
28­
32
pregnant
Sprague­
Dawley
rats/
dose/
phase
group
in
the
diet
at
dose
levels
of
0,
0.025%,
0.050%,
0.075%,
0.10%
or
0.20%
(
equivalent
to
average
daily
intakes
of
0,
19,
36,
55,
76
or
143
mg/
kg
bw/
day
boric
acid;
0,
3.3,
6.3,
9.6,
13.3
or
25
mg/
kg/
day
boron
equivalents)
from
days
0
through
20
of
gestation.
The
study
was
conducted
in
two
phases:
in
phase
I,
developmental
toxicity
was
examined
in
fetuses
from
dams
sacrificed
on
GD
20.
In
Phase
II,
dams
were
allowed
to
deliver
and
dams
and
pups
sacrificed
on
postnatal
day
21
for
evaluation
of
persistence
of
developmental
effects.

Maternal
toxicity:
At
0.2%,
slightly
reduced
gravid
uterine
weight
was
observed
(­
10%,
not
significant);
uncorrected
and
corrected
body
weight
gains
were
not
affected.
The
decrease
was
considered
secondary
to
decreased
fetal
weights.
There
were
no
treatment­
related
effects
on
survival,
clinical
signs
or
cesarean
parameters.
The
maternal
NOAEL
is
143
mg/
kg
bw/
day
boric
acid
(
25
mg/
kg/
day
boron
equivalents;
HDT)(
slightly
reduced
gravid
uterine
weight
was
considered
secondary
to
reduced
fetal
weight
and
not
a
maternally
toxic
effect).
A
maternal
LOAEL
was
not
determined
in
this
study.

Developmental
toxicity
(
Study
Phase
I):
At
0.1%,
decreased
fetal
body
weight
(­
6.1%,
male
pups
and
­
7.1%,
female
pups,
both
p<
0.05)
and
increased
incidence
of
short
rib
XIII
(
fetal
17%
vs.
9%,
controls)
and
wavy
rib
(
fetal
10%
and
litter
6%
vs
0%,
controls;
all
p<
0.05)
were
observed.
The
developmental
LOAEL
is
76
mg/
kg
bw/
day
boric
acid
(
13.3
mg/
kg/
day
boron
equivalents),
based
on
decreased
fetal
weight
and
increased
incidence
(
fetal
and
litter)
of
short
rib
XIII
and
wavy
rib.
The
developmental
NOAEL
is
55
mg/
kg
bw/
day
boric
acid
(
9.6
mg/
kg/
day
boron
equivalents).
Page
26
of
84
Phase
II
(
postnatal
evaluation)­
At
0.1%
(
13
mg/
kg/
day
boron),
no
effects
on
pup
weight
or
skeletal
abnormalities
were
observed
at
the
Day
21
postnatal
sacrifice.
At
0.2%
(
25
mg/
kg/
day
boron),
an
increased
incidence
of
short
rib
XIII
was
observed;
pup
weights
were
unaffected.

This
developmental
toxicity
study
in
the
rat
is
classified
acceptable
(
nonguideline)
and
satisfies
the
guideline
requirement
for
a
developmental
toxicity
study
(
OPPTS
870.3700;
OECD
414)
in
the
rat.
The
test
material
was
administered
via
the
dietary
route
instead
of
by
gavage
and
beginning
on
GD
0
instead
of
GD6
to
imitate
human
dietary
exposure
but
is
considered
acceptable
for
regulatory
purposes.

(
3)
Rabbit:
In
a
developmental
toxicity
study
(
MRID
42164201
and
­
02),
boric
acid
(
technical,
99%
a.
i.)
was
administered
to
30
pregnant
(
artificially
inseminated)
New
Zealand
White
rabbits/
dose
by
gavage
(
5
mL/
kg
dose
volume)
at
dose
levels
of
0,
62.5,
125
or
250
mg/
kg/
day
from
days
6
through
19
of
gestation,
inclusive
(
equivalent
to
0,
11,
22
or
44
mg/
kg/
day
of
boron
equivalents).

Maternal
toxicity:
At
250
mg/
kg/
day,
does
showed
weight
loss
during
treatment
(­
137
g
vs.
gain
of
+
93
g,
controls
due
primarily
to
decreased
gravid
uterine
weight,
based
on
corrected
weight
gain
and
fetal
loss),
an
increased
incidence
of
vaginal
bleeding
(
GD
19­
30;
15
does
with
bleeding
had
no
live
fetuses),
and
increased
relative
kidney
weights.
The
maternal
weight
effects
are
considered
secondary
to
reduced
fetal
survival.
Although
the
vaginal
bleeding
was
also
associated
with
reduced
fetal
survival,
it
was
considered
a
possible
maternally
toxic
effect
because
it
could
have
resulted
from
a
direct
maternal
effect.
It
is
noted
that
several
animals
were
removed
from
the
study
for
technical
reasons:
6
controls
and
3
from
each
of
the
other
dose
groups
due
to
food
access
problems
(
leaky
water
bottles,
feeder
knocked
off
cage),
and
3
mid
dose
animals
due
to
dosing
trauma.
The
maternal
LOAEL
is
250
mg/
kg
bw/
day
(
44
mg/
kg/
day
boron
equivalents),
based
on
an
increased
incidence
of
vaginal
bleeding.
The
maternal
NOAEL
is
125
mg/
kg
bw/
day
(
22
mg/
kg/
day
boron
equivalents).

Developmental
Toxicity:
At
250
mg/
kg/
day,
the
number
of
resorptions/
dam
was
increased
(
7.8
vs.
0.72,
controls);
most
were
early
(
total
140
compared
to
4,
controls,
but
late
also
showed
an
increase
of
16
vs.
9,
controls),
mean
fetal
weight
was
decreased
by
­
8.3%
(
not
significant)
and
live
fetuses/
dam
was
decreased
to
2.3
vs.
8.8,
controls.
Postimplantation
loss
was
92.6%
compared
to
7%,
controls.
The
percentage
of
male
fetuses
was
greater
at
69%
vs.
50%,
controls
(
not
significant).
Visceral
abnormalities
included
enlarged
aorta,
intraventricular
septal
defect
and
abnormal
position
of
pulmonary
vein.
The
incidence
of
agenesis
of
the
gallbladder
was
also
increased.
[
Note:
at
125
mg/
kg/
day
a
low
incidence
of
agenesis
of
the
gallbladder
was
observed,
3/
153
pups,
which
is
noted
but
was
not
used
to
establish
the
LOAEL
for
developmental
toxicity
due
to
low
incidence
and
lack
of
other
abnormalities.
However,
it
is
a
relatively
rare
malformation].
The
developmental
LOAEL
is
250
mg/
kg
bw/
day
(
44
mg/
kg/
day
boron
equivalents),
based
on
increased
fetal
resorptions
and
mortality
and
increased
incidence
of
visceral
abnormalities.
The
developmental
NOAEL
is
125
mg/
kg/
day
(
22
mg/
kg/
day
boron
equivalents).
Page
27
of
84
The
developmental
toxicity
study
in
the
rabbit
is
classified
acceptable
(
guideline)
and
satisfies
the
guideline
requirement
for
a
developmental
toxicity
study
(
OPPTS
870.3700;
OECD
414)
in
the
rabbit.

(
4)
Mouse:
In
a
developmental
toxicity
study
(
MRID
41725402),
boric
acid
(
98­
99%
a.
i.)
was
administered
to
28­
29
pregnant
Crl:
CD­
1(
ICR)
VAF/
Plus
outbred
Swiss
albino
mice/
dose
in
the
diet
at
dose
levels
of
0,
0.1%,
0.2%
or
0.4%
from
gestation
days
0
through
17
(
equivalent
to
an
average
daily
dose
of
0,
248,
452
or
1003
mg/
kg/
day
boric
acid;
0,
43,
79
or
176
mg/
kg/
day
boron
equivalents).
Microscopic
evaluation
of
the
kidneys
was
performed
on
10
dams/
dose
group.

Maternal
toxicity:
At
0.1%,
an
increased
incidence
of
renal
tubular
dilatation
was
reported
(
from
control
to
high
dose,
0/
10,
2/
10,
8/
10
and
10/
10,
respectively).
At
0.4%,
maternal
body
weight
gain
was
significantly
reduced
(­
21%
below
controls),
although
corrected
weight
gains
were
unaffected.
Relative
kidney
weights
(
left
and
right
individually)
were
significantly
increased
by
about
30%
(
left
kidney
absolute
weights
also
increased
by
15%),
with
pale
kidneys
observed
grossly.
A
transient
increase
in
food
and
water
consumption
(
both
+
15%)
was
reported
on
Days
15­
17.
There
were
no
treatment­
related
effects
on
clinical
signs
or
mortality.
The
maternal
LOAEL
is
0.1%
(
248
mg/
kg
bw/
day
boric
acid;
43
mg/
kg/
day
boron
equivalents),
based
on
renal
pathology.
A
maternal
NOAEL
was
not
established
in
this
study.

Developmental
toxicity:
At
0.2%,
mean
fetal
weight
was
significantly
reduced
(
about
­
10%
below
controls)
and
the
percent
with
short
rib
XIII
per
litter
was
increased
(
7.5%
increasing
to
20%
at
0.4%,
compared
to
0%
in
controls).
At
0.4%,
the
percent
of
litters
with
resorptions
and
%
resorptions
per
litter
were
increased
(+
65%
and
+
216%,
respectively).
The
developmental
LOAEL
is
0.2%
(
452
mg/
kg
bw/
day
boric
acid;
79
mg/
kg/
day
boron
equivalents),
based
on
decreased
fetal
weight
and
increased
incidence
of
short
rib
XIII.
The
developmental
NOAEL
is
0.1%
(
248
mg/
kg/
day
boric
acid;
43
mg/
kg
bw/
day
boron
equivalents).

This
developmental
toxicity
study
in
the
mouse
is
classified
acceptable
(
nonguideline)
and
satisfies
the
guideline
requirement
for
a
developmental
toxicity
study
(
OPPTS
870.3700;
OECD
414)
in
the
rodent.
The
test
material
was
administered
in
the
diet
instead
of
by
gavage
to
mimic
human
dietary
exposure.
The
study
is
considered
acceptable
for
regulatory
purposes.

4.2.4
Reproductive
Toxicity
Study
(
1)
In
an
oral
three­
generation
reproduction
study
(
MRID
40692311),
sodium
decaborate
tetrahydrate
(
borax
tech.,
analyzed
at
103­
105%
of
theoretical
boron
content)
was
administered
to
8
male
and
16
female
Charles
River
CD
rats/
dose
in
the
diet
at
continuous
dose
levels
of
0,
0.103%,
0.308%
or
1.03%
(
in
males,
equivalent
to
0,
0,
72,
218
or
729
mg/
kg/
day
test
material
and
0,
8.1,
25
or
82
mg/
kg/
day
boron
equivalents;
in
females,
equivalent
to
0,
81,
241
or
814
Page
28
of
84
mg/
kg/
day
test
material
and
0,
9.2,
27
or
92
mg/
kg/
day
boron
equivalents).
After
a
14­
week
premating
period,
one
male
and
two
females
were
mated
for
up
to
21
days.
Two
matings
per
generation
were
performed
to
produce
two
litters.
An
exception
to
the
protocol
was
taken
for
the
1.03%
P1
repeat
matings
due
to
no
conceptions
in
the
first
mating:
untreated
males
were
used
with
the
treated
females
for
the
subsequent
P1
matings.
The
high
dosing
group
was
not
continued
for
P2
and
P3
generations
due
to
insufficient
successful
matings
from
either
attempted
P1
mating.

Parental
toxicity:
At
1.03%,
clinical
signs
(
coarse
fur,
scaly
tails,
hunched
posture)
and
decreased
premating
body
weight
gain
were
observed
in
P1
males
(­
14%
below
controls)
and
females
(­
15%)
(
but
not
in
later
parental
generations).
Testicular
atrophy
with
severely
decreased
testes
abs/
rel
weights
was
observed
in
all
P1
males.
In
females,
the
number
of
functioning
ovaries
was
lower
than
normal
(
4/
15),
although
the
controls
were
not
examined
for
comparison.
No
subsequent
generations
were
tested
at
this
dose
level.
The
parental
toxicity
LOAEL
is
1.03%
(
males/
females
729/
814
mg/
kg/
day
test
material;
82/
92
mg/
kg/
day
boron
equivalents),
based
on
clinical
signs,
decreased
weight
and
testicular
atrophy/
reduced
ovarian
function.
The
NOAEL
is
0.308%
(
males/
females
218/
241
mg/
kg/
day
test
material;
25/
27
mg/
kg/
day
boron
equivalents).

Offspring
toxicity:
At
1.03%,
no
litters
were
born.
In
the
second
mating
with
untreated
males,
there
were
only
2
litters
and
1
abortion;
no
pups
survived
past
Day
3
postpartum
(
died
or
cannibalized).
The
offspring
toxicity
LOAEL
is
1.03%
(
males/
females
729/
814
mg/
kg/
day
test
material;
82/
92
mg/
kg/
day
boron
equivalents),
based
on
mortality.
The
NOAEL
is
0.308%
(
males/
females
218/
241
mg/
kg/
day
test
material;
25/
27
mg/
kg/
day
boron
equivalents).

Reproductive
toxicity:
At
1.03%,
no
litters
were
produced
in
the
first
P1
mating.
The
second
P1
mating
with
untreated
males
resulted
in
2
litters
and
1
abortion
out
of
16
matings.
All
pups
were
either
cannibalized
or
died
by
Day
3
postpartum.
Testes
of
parental
P1
males
showed
complete
atrophy
and
P1
females
had
a
lower
than
normal
number
of
functioning
ovaries
(
4/
15
with
corpora
lutea;
however
controls
were
not
examined);
the
study
authors
concluded
that
the
latter
finding
was
insufficient
to
completely
account
for
the
low
fertility
observed
with
untreated
males
and
that
some
other
effect
on
ovarian
function
or
implantation
was
occurring.
The
reproductive
toxicity
LOAEL
is
1.03%
(
males/
females
729/
814
mg/
kg/
day
test
material;
82/
92
mg/
kg/
day
boron
equivalents),
based
on
reduced
fertility.
The
NOAEL
is
0.308%
(
males/
females
218/
241
mg/
kg/
day
test
material;
25/
27
mg/
kg/
day
boron
equivalents).

This
study
is
classified
as
acceptable
(
nonguideline)
and
satisfies
the
guideline
requirement
for
a
multi­
generation
reproductive
study
(
OPPTS
870.3800;
OECD
416)
in
the
rodent
(
rat).
Although
the
study
had
several
deficiencies
(
incomplete
histopathology
evaluation,
2:
1
matings,
less
than
20
pregnant
females/
group,
lack
of
gestation
period
data
and
low
lactation
indices
in
control
animals),
the
data
are
considered
acceptable
for
regulatory
purposes
and
a
new
study
is
not
required
at
this
time,
based
on
consideration
of
this
data
together
with
other
studies
on
reproductive/
developmental
toxicity
and
systemic
toxicity
in
the
rat.
Page
29
of
84
(
2)
In
an
oral
three­
generation
reproductive
toxicity
study
(
MRID
00068882),
boric
acid
(
technical
grade,
$
98.7%
a.
i.)
was
administered
continuously
in
the
diet
to
8
male
and
16
female
Sprague
Dawley
rats/
dose
at
concentrations
of
0,
0.067%,
0.20%
or
0.67%
(
equivalent
to
average
daily
boron
intakes
of
0,
8.5,
26.6
or
85
mg/
kg/
day,
males
and
0,
9.7,
29
or
91.6
mg/
kg/
day,
females).
Matings
(
2
females
per
male)
were
conducted
over
three
generations,
with
two
matings
performed
per
generation.
The
high
dosing
group
was
not
continued
for
P2
and
P3
generations
due
to
lack
of
litters.

Parental
toxicity:
At
0.67%,
clinical
signs
of
toxicity
were
reported,
body
weights
of
males
and
females
were
decreased
and
at
autopsy,
testes
of
males
were
visibly
atrophied
(
not
examined
microscopically
but
confirmed
by
lack
of
spermiation
in
other
feeding
studies).
About
half
of
the
females
showed
evidence
of
reduced
ovulation.
The
parental
toxicity
LOAEL
is
0.67%
(
85/
92
mg/
kg/
day
boron
equivalents),
based
on
clinical
signs
of
toxicity,
decreased
body
weights,
testicular
atrophy
and
reduced
ovulation.
The
NOAEL
is
0.20%
(
27/
29
mg/
kg/
day
boron
equivalents).

Reproductive
toxicity:
At
0.67%,
no
litters
were
produced.
As
noted
for
parental
toxicity,
testes
were
atrophied
and
ovaries
showed
signs
of
reduced
ovulation.
A
cross­
mating
of
the
treated
females
with
males
administered
untreated
diet
was
unsuccessful,
indicating
effects
on
the
female
reproductive
system
as
well
as
the
male
(
the
authors
did
not
consider
the
reduced
ovulation
sufficient
to
explain
the
complete
lack
of
fertility,
indicating
a
more
pronounced
effect
on
males).
The
reproductive
toxicity
LOAEL
is
0.67%
(
85/
92
mg/
kg/
day
boron
equivalents),
based
sharply
reduced
fertility
related
to
testicular
atrophy,
reduced
ovulation
and
probably
other
effects.
The
NOAEL
is
0.20%
(
27/
29
mg/
kg/
day
boron
equivalents).

Offspring
toxicity:
At
0.67%,
no
litters
were
produced.
A
cross­
mating
of
treated
females
with
untreated
males
resulted
in
reduced
numbers
of
P1
litters
and
pup
survival.
The
offspring
toxicity
LOAEL
is
0.67%
(
85/
97
mg/
kg/
day
boron
equivalents),
based
on
reduced
pup
survival
from
a
treated
female/
untreated
male
mating.
The
NOAEL
is
0.20%
(
27/
29
mg/
kg/
day
boron
equivalents).

This
study
is
classified
acceptable
(
nonguideline)
and
satisfies
the
guideline
requirement
for
a
multi­
generation
reproductive
study
(
OPPTS
870.3800;
OECD
416)
in
the
rodent
(
rat).
Although
the
study
had
several
deficiencies
(
incomplete
histopathology
evaluation,
2:
1
matings,
less
than
20
pregnant
females/
group,
lack
of
gestation
period
data
and
low
lactation
indices
in
control
animals),
the
data
are
considered
acceptable
for
regulatory
purposes
and
a
new
study
is
not
required
at
this
time,
based
on
consideration
of
this
data
together
with
other
studies
on
reproductive/
developmental
toxicity
and
systemic
toxicity
of
boron
in
the
rat.

(
3)
In
a
two­
generation
oral
reproduction
study
(
MRID
41589101),
boric
acid
(
99%
a.
i.,
batch/
lot
#
872703)
was
administered
in
the
diet
to
38
CD­
1
Swiss
mice/
sex
at
0
mg/
kg/
day
and
to
19­
20
CD­
1
Swiss
mice/
sex/
dose
at
continuous
dose
levels
of
0,
1000,
4500
or
9000
ppm
Page
30
of
84
(
equivalent
to
0,
152,
636
or
1262
mg/
kg/
day
test
material
and
0,
27,
111
or
221
mg/
kg/
day
boron
equivalents).
For
the
F1
generation,
only
0
and
1000
ppm
doses
were
administered
due
to
reduced
fertility
at
the
higher
doses.
The
study
was
performed
by
NTP
according
to
the
reproductive
assessment
by
continuous
breeding
(
RACB)
protocol.
Animals
were
given
a
one
week
premating
period
and
a
14­
week
cohabitation
period,
followed
by
a
holding
period.
Litters
born
during
cohabitation
were
removed
by
24
hr
postpartum;
those
born
later
remained
with
the
dams
for
21
days.
In
addition,
a
cross­
over
mating
period
between
20/
sex/
dose
of
control
and
mid
dose
males
and
females
to
determine
the
affected
sex
and
an
offspring
assessment,
in
which
F1
offspring
from
the
continuous
F0
mating
litters
were
selected,
were
performed.

Parental
toxicity:
At
4500
ppm
(
F0
parental
animals
only),
decreased
body
weight
in
females
(
at
week
18,
­
23%;
considered
largely
secondary
to
lower
fertility
rather
than
direct
toxicity)
and
sharply
decreased
abs/
rel
testes
weight
(­
40
to­
50%
of
controls)
and
degeneration
of
seminiferous
tubules
(
17/
20
males)
were
observed;
a
decrease
in
cauda
epididymides
and
prostate
weights
were
also
noted.
Sperm
showed
a
significantly
lower
concentration
per
mg
caudal
tissue
(­
72%),
motility
( 
32%)
and
a
higher
percentage
of
abnormal
sperm
(
61%
vs.
11%,
controls).
A
slight
but
statistically
significant
reduction
in
adrenal/
kidney
weight
was
also
observed
in
females
(­
9%).
At
9000
ppm,
mean
body
weight
gain
was
significantly
decreased
in
males
and
females.
In
addition
to
severe
reduction
in
testicular
weights
and
seminiferous
tubule
atrophy,
12/
15
males
produced
no
sperm
and
those
that
did
had
only
50%
of
sperm
being
motile.
Lacrimation,
exophthalmos
and
cloudiness
of
the
eyes
were
observed.
A
parental
systemic
LOAEL
is
4500
ppm
(
636
mg/
kg/
day
test
material;
111
mg/
kg/
day
boron
equivalents),
based
on
decreased
testicular
weight
in
males
and
possibly
adrenal/
kidney
weight
decrease
in
females.
The
parental
systemic
NOAEL
is
1000
ppm
(
152
mg/
kg
bw/
day
test
material;
27
mg/
kg/
day
boron
equivalents).

Offspring
toxicity:
At
4500
ppm
(
F1
pups
only),
mean
pup
weight
was
decreased
(­
14%
below
controls)
and
reductions
in
the
average
number
of
litters
per
pair
(
2.3
vs.
4.7,
controls),
number
of
live
pups
per
litter
(
8.67
vs.
13.52,
controls)
and
%
alive
(­
11%)
were
observed.
The
offspring
LOAEL
is
4500
ppm
(
636
mg/
kg/
day
test
material;
111
mg/
kg/
day
boron
equivalents),
based
on
reduced
pup
weight
and
lower
survival.
The
offspring
NOAEL
is
1000
ppm
(
152
mg/
kg
bw/
day
test
material;
27
mg/
kg/
day
boron
equivalents).

Reproductive
toxicity:
At
4500
ppm
(
F0
mating
only),
fertility
was
sharply
reduced
(
44%
vs.
94%,
controls).
The
number
of
days
to
litter
in
the
F0
continuous
breeding
portion
increased
after
the
second
litter,
with
the
number
of
dams
producing
litters
and
live
pups
per
litter
also
decreasing
with
each
litter.
In
the
crossover
mating
evaluation,
mating/
fertility
indices
were
sharply
reduced
in
matings
of
treated
males
with
control
females
(
30%/
5%
vs.
79%/
74%,
controls)
but
also
slightly
affected
in
matings
of
treated
females
with
control
males
(
70%/
64%),
thereby
indicating
that
although
effects
were
greater
on
males,
some
effect
on
females
was
also
present.
Testicular
effects
are
described
under
parental
toxicity,
above.
At
9000
ppm,
no
litters
were
produced
and
males
showed
decreased
sperm
concentration
and
motility,
as
described
above
under
parental
toxicity.
The
reproductive
LOAEL
is
4500
ppm
(
636
mg/
kg/
day
test
material;
Page
31
of
84
111
mg/
kg/
day
boron
equivalents),
based
on
reduced
fertility
and
reduced
sperm
concentration.
The
reproductive
NOAEL
is
1000
ppm
(
152
mg/
kg
bw/
day
test
material;
27
mg/
kg/
day
boron
equivalents).

This
study
is
classified
as
acceptable
(
nonguideline)
and
satisfies
the
guideline
requirement
for
a
multi­
generation
reproductive
study
(
OPPTS
870.3800;
OECD
416)
in
the
rodent
(
mouse).
The
study
was
not
conducted
according
to
Agency
guidelines
and
some
deficiencies
are
noted
(
including
only
one
dose
level
in
the
P1
mating,
incomplete
histopathology,
nonguideline
mating
protocol).
However,
this
study,
conducted
by
the
NTP,
provides
sufficient
information
to
characterize
the
reproductive
toxicity
of
boric
acid
and
is
considered
acceptable
for
regulatory
purposes.

4.2.5
Additional
Information
from
Literature
Sources
Several
studies
have
investigated
the
mechanism
of
axial
skeletal
defect
formation
in
the
developing
rat.
Narotsky
et
al.
(
2003)
dosed
rat
dams
with
500
mg/
kg
boric
acid
twice/
day
on
single
days
of
gestation
(
6
through
11).
Using
in
situ
hybridization,
it
was
demonstrated
that
exposure
on
GD
9
caused
alterations
in
the
expression
of
homeotic
genes
hoxc6
and
hoxa6
that
occurred
along
with
increased
elevation
of
rudimentary
cervical
ribs.
Single
exposures
on
GD
8,
9
or
10
all
caused
axial
skeletal
defects.
Reduction
of
fetal
weight
but
not
skeletal
effects
was
observed
with
dosing
on
GD
7
and
11.
The
role
of
hox
genes
in
developmental
of
axial
skeletal
defects
and
confirmation
of
GD9
as
a
sensitive
window
of
development
was
supported
by
a
second
study
by
Wery
et
al.
(
2003),
who
found
alterations
in
expression
of
hoxd4,
hoxa4,
hoxc5
and
hoxc6
in
the
somites
responsible
for
cranial­
caudal
axial
skeletal
development.
These
studies
would
appear
to
support
the
conclusion
that
a
single
exposure
at
a
critical
developmental
stage
could
cause
developmental
defects.
However,
effects
on
hox
genes
have
not
been
evaluated
at
lower
dose
levels
and
therefore
the
significance
of
this
finding
at
doses
relevant
to
human
exposure
is
not
known
at
this
time.

The
mechanism
of
testicular
toxicity
(
reduced
spermiation,
atrophy)
is
also
not
well
understood.
Studies
have
been
conducted
to
evaluate
the
effects
of
boron
on
the
testes
of
the
rat
(
Ku
and
Chapin,
1994).
In
the
rat,
boron
causes
a
slight
inhibition
of
plasma
testosterone
that
is
not
considered
sufficient
to
result
in
atrophy.
The
data
suggest
a
possible
CNS­
mediated
effect
of
boron
on
the
testes,
based
on
lack
of
effect
on
steroidogenic
function
of
Leydig
cells
in
in
vitro
studies.
The
most
sensitive
in
vitro
endpoint
was
DNA
synthesis
of
mitotic/
meiotic
germ
cells
in
Sertoli
cell/
germ
cell
cultures,
with
energy
metabolism
of
Sertoli
cells
also
affected.
Further
work
is
needed
to
fully
characterize
the
mechanism
of
toxicity.

4.2.6
Pre­
and/
or
Postnatal
Toxicity
4.2.6.1
Determination
of
Susceptibility
There
is
evidence
of
increased
developmental
susceptibility
to
boric
acid
and
its
sodium
Page
32
of
84
salts,
based
on
fetal
toxicity
(
reduced
fetal
body
weight
and
skeletal
developmental
abnormalities)
observed
in
the
rat
at
doses
below
maternally
toxic
levels.
In
the
rabbit
and
mouse
developmental
toxicity
studies,
developmental
toxicity
was
observed
at
doses
causing
maternal
effects.

4.2.6.2
Degree
of
Concern
Analysis
and
Residual
Uncertainties
for
Pre
and/
or
Post­
natal
Susceptibility
Although
fetal
toxicity
is
observed
at
doses
below
maternally
toxic
levels
in
the
rat,
developmental
toxicity
has
been
well­
characterized
in
four
developmental
toxicity
studies
in
three
species.
Rabbits
and
mice
did
not
demonstrate
clearly
increased
fetal
sensitivity,
although
developmental
toxicity,
including
skeletal
or
visceral
abnormalities
and
reduced
fetal
survival,
was
observed.
Reproductive
toxicity
studies
in
two
species
are
also
available.
The
mechanism
of
testicular
effects
(
inhibited
spermiation,
testicular
atrophy)
has
not
been
characterized,
but
the
lack
of
effects
on
male
reproductive
function
in
the
rat
and
mouse
reproductive
toxicity
studies
at
doses
greater
than
the
endpoint
used
for
this
risk
assessment
suggests
that
there
is
not
increased
sensitivity
of
the
developing
testes.
At
this
time,
there
are
no
residual
uncertainties,
based
on
sufficient
data
to
characterize
the
developmental
effects.
The
NOAEL
used
for
risk
assessments
is
lower
than
the
rat
developmental
toxicity
NOAEL
that
is
the
most
sensitive
developmental
endpoint
and
is
the
most
sensitive
endpoint
identified
from
the
available
data.

4.3
Recommendation
for
a
Developmental
Neurotoxicity
Study
4.3.1
Evidence
that
supports
requiring
a
Developmental
Neurotoxicity
study
Enlarged
lateral
ventricles
of
the
brain
were
reported
in
a
rat
developmental
toxicity
study.
Acute
exposure
to
higher
doses
of
boron
compounds
may
induce
neurological
symptoms.
Case
reports
of
infants
poisoned
with
boric
acid/
borax
show
convulsions
and
other
neurological
signs
of
toxicity
and
in
the
case
of
some
that
died,
brain
pathology.

4.3.2
Evidence
that
supports
not
requiring
a
Developmental
Neurotoxicity
study
Evidence
of
clinical
signs
of
neurotoxicity
occurs
at
high
dose
levels
that
are
above
the
exposure
levels
causing
other
signs
of
toxicity.
There
was
no
clear
evidence
of
unequivocal
neurotoxicity
in
adult
animals
in
the
available
studies.
Developmental
effects
on
the
brain
(
enlarged
lateral
ventricles)
were
observed
in
the
rat
at
doses
above
those
causing
the
most
sensitive
effects
(
skeletal
variations
and
malformations).

4.3.3
Rationale
for
the
UFDB
(
when
a
DNT
is
recommended)

At
this
time
a
DNT
study
is
not
recommended
and
a
database
uncertainty
factor
is
not
required.
Page
33
of
84
4.4
Hazard
Identification
and
Toxicity
Endpoint
Selection
Boric
acid
and
its
sodium
salts
are
exempt
from
tolerances
because
boron
is
present
at
endogenous
levels
in
plants
that
are
higher
than
the
contribution
from
pesticidal
products
applied
to
crops.
Boron
does
not
accumulate
in
animal
tissues.
A
dietary
risk
assessment
is
therefore
not
required
at
this
time
(
see
Sections
6.1
and
6.2,
below
for
additional
discussion).

4.4.1
Acute
and
Chronic
Reference
Doses
(
aRfD
and
cRfD)

Reference
doses
for
acute
and
chronic
exposure
were
not
selected
for
this
risk
assessment
because
dietary
(
food
plus
drinking
water)
risk
assessments
were
not
performed.

It
is
noted
that
chronic
dietary
or
drinking
water
reference
doses
have
been
selected
by
several
reviewing
groups.
For
example,
the
U.
S.
EPA
IRIS
(
2004)
selected
an
RfD
of
0.2
mg/
kg/
day,
based
on
a
benchmark
dose
lower
limit
of
the
95th
percentile
confidence
interval
for
a
5%
decrease
in
fetal
body
weight
(
BMDL
05
)
of
10.3
mg/
kg/
day
from
the
two
rat
developmental
toxicity
studies
and
a
combined
uncertainty
factor
(
UF)
of
66.
ECETOC
(
1994)
and
the
National
Academy
of
Sciences
Food
and
Nutrition
Board
(
2001)
both
determined
a
tolerable
daily
intake
(
TDI)
of
0.32
mg/
kg/
day
using
the
developmental
toxicity
NOAEL
of
9.6
mg/
kg/
day
from
the
rat
developmental
toxicity
study
of
Price
et
al.
(
MRID
43340101)
and
a
combined
UF
of
30.
WHO
(
1998)
selected
a
TDI
of
0.4
mg/
kg/
day,
based
on
the
developmental
toxicity
NOAEL
of
9.6
mg/
kg/
day
and
a
combined
UF
of
25.

4.4.2
Incidental
Oral,
Short­
and
Intermediate­
Term
Exposures
(
All
Populations)

Studies
selected:
90­
day,
38­
week
and
2­
year
dietary
studies
in
the
dog
MRID
Nos.:
40692307,
40692308,
40692310
Executive
Summaries:

(
1)
In
a
chronic
toxicity
study
(
MRID
40692310),
sodium
tetraborate
decahydrate
(
technical
borax,
purity
100%
a.
i.)
was
administered
to
four
beagle
dogs/
sex/
dose
in
the
diet
at
dose
levels
of
0,
0.051%,
0.103%
or
0.309%
(
equivalent
to
average
daily
intakes
of
0,
13,
26
or
77
mg/
kg/
day
test
material;
0,
1.5,
2.9
or
8.8
mg/
kg/
day
boron
equivalents)
for
104
weeks.
One
male
and
one
female/
group
were
sacrificed
at
week
52
for
interim
evaluation;
one
male
and
one
female
from
the
control
and
high
dose
groups
were
sacrificed
at
week
117
for
a
recovery
assessment,
with
removal
of
test
diet
at
week
104.
Only
limited
clinical
chemistry
parameters
were
evaluated
and
ophthalmologic
examinations
were
not
performed.

There
were
no
effects
observed
on
mortality,
clinical
signs,
body
weight,
food
consumption,
hematology,
clinical
chemistry,
organ
weights
or
gross/
microscopic
pathology
that
were
considered
to
be
clearly
associated
with
treatment.
At
0.304%,
reduced
sperm
counts
were
Page
34
of
84
reported
and
one
male
at
the
52­
week
sacrifice
showed
signs
of
testicular
atrophy
and
reduced
testicular
weight.
The
study
pathologist
reported
that
the
finding
appeared
to
be
of
recent
origin
and
probably
unrelated
to
treatment.
The
NOAEL
is
0.304%
(
77
mg/
kg/
day
test
material;
8.8
mg/
kg/
day
boron
equivalents)
(
HDT).
A
LOAEL
was
not
determined
in
this
study.

This
chronic
study
in
the
dog
is
classified
as
acceptable
(
nonguideline)
and
satisfies
the
guideline
requirement
for
a
chronic
oral
study
[
OPPTS
870.4100,
OECD
452]
in
the
dog
when
considered
together
with
MRID
40692308,
a
38­
week
dietary
dog
study
(
HED
TXR
#
009301),
which
establishes
a
clear
effect
level.
Although
this
two
year
dietary
study
in
the
dog
was
originally
classified
as
"
Supplementary"
due
to
lack
of
effects,
the
HED
RfD
Committee
determined
that
taken
together
with
the
38­
week
study
and
the
90­
day
study,
there
are
sufficient
data
to
adequately
characterize
the
chronic
toxicity
of
borate
to
the
dog
(
memoranda
dated
November
24,
1993
and
June
12,
1995).

(
2)
In
a
chronic
toxicity
study
(
MRID
40692308),
sodium
tetraborate
decahydrate
(
borax
technical)
was
administered
to
4
beagle
dogs/
sex/
dose
in
the
diet
at
dose
levels
of
0
or
1.03%
(
for
males/
females,
equivalent
to
0
or
348/
400
mg/
kg/
day
test
material;
0
or
40/
46
mg/
kg/
day
boron
equivalents)
for
up
to
38
weeks.
Two
animals/
dose/
sex
were
sacrificed
at
week
26,
one
treated
male
and
female
and
two
controls/
sex
at
week
38
and
one
treated
animal/
sex
was
maintained
on
basal
diet
for
a
three
week
recovery
phase
and
sacrificed
at
week
41.

At
1.03%,
decreased
body
weight
gain
was
observed
in
males
and
females
(­
10
to
­
11%
below
controls).
In
males,
testicular
atrophy
and
decreased
testicular
weight
were
observed.
At
26
weeks,
2/
2
males
showed
generalized
spermatogenic
arrest
at
the
spermatocyte
stage,
progressing
to
complete
atrophy
of
the
seminiferous
epithelium
in
some
tubules,
whereas
½
controls
showed
scattered
atrophy.
At
38
weeks,
1
control
male
showed
severe
degeneration
of
the
seminiferous
tubules
and
1
showed
10­
15%
of
tubules
undergoing
degenerative
changes;
1
treated
male
showed
5­
10%
of
the
tubules
undergoing
degenerative
changes.
At
41
weeks,
1
treated
male
showed
a
moderate
tubular
degeneration
and
evidence
of
complete
cessation
of
spermatogenesis.
Absolute
and
relative
testicular
weights
of
treated
animals
were
also
reduced
(­
35%
to
­
45%).
No
increases
in
boron
levels
were
reported
in
blood,
brain,
liver,
fat,
kidney
or
muscle
in
dogs
sacrificed
at
26
or
38
weeks,
but
an
increase
in
urinary
boron
was
observed.
Excretion
was
complete
before
4
days
after
cessation
of
treatment.
There
were
no
treatmentrelated
effects
on
survival,
clinical
signs
of
toxicity.
The
LOAEL
is
1.03%
(
40/
46
mg/
kg/
day,
males/
females),
based
on
decreased
body
weight
gain
in
males
and
females
and
testicular
atrophy
in
males.
A
NOAEL
was
not
determined
in
this
study.

This
chronic
study
in
the
dog
is
classified
acceptable
(
nonguideline)
when
considered
together
with
the
findings
of
a
two­
year
dietary
study
in
the
dog
(
MRID
40692310);
by
itself
it
does
not
satisfy
the
guideline
requirement
for
a
chronic
oral
study
[
OPPTS
870.4100,
OECD
452]
in
the
dog.
Only
a
single
dose
was
tested,
a
small
number
of
animals
were
available
for
each
time
point
evaluation
and
only
limited
clinical
chemistry
parameters
were
evaluated.
At
this
time,
the
data
requirement
for
a
chronic
oral
toxicity
study
in
the
dog
is
considered
to
be
satisfied
and
Page
35
of
84
no
additional
data
are
required.

(
3)
In
a
subchronic
oral
toxicity
study
(
MRID
40692307),
sodium
tetraborate
decahydrate
(
technical
borax,
analyzed
at
105%
of
theoretical)
was
administered
for
13
weeks
to
5
beagle
dogs/
sex/
dose
in
the
diet
at
dose
levels
of
0,
0.0154,
0.154
or
1.54%
(
in
males,
equivalent
to
average
daily
intakes
of
0,
2.9,
35
or
268
mg/
kg/
day
test
material
and
0,
0.34,
4.1
or
32
mg/
kg/
day
boron
equivalents;
in
females,
to
0,
2.1,
22
or
192
mg/
kg/
day
test
material;
0,
0.25,
2.6
or
23
mg/
kg/
day
boron
equivalents).
Clinical
chemistry
evaluations
were
limited
to
blood
urea
nitrogen
and
non­
fasting
glucose,
and
urinalysis.

At
1.54%,
testicular
atrophy
and
reduced
testes
weight
in
males,
slightly
but
statistically
significantly
decreased
hematocrit/
hemoglobin
at
13
weeks
(­
15%/­
11%
males
and
­
6%/­
11%
females)
and
increased
hemosiderin
pigment
in
spleen,
liver
and
kidneys
were
observed.
An
increase
in
the
width
of
the
adrenal
cortex
in
females
and
a
slight
increase
in
epithelial
nests
of
the
thyroid
in
males
were
reported;
slightly
widened
adrenal
cortex
in
females
and
slightly
increased
proportion
of
epithelial
nests
in
males
were
also
reported
at
0.154%
but
were
of
uncertain
toxicological
significance
and
were
not
used
to
establish
the
LOAEL
for
this
study.
There
were
no
treatment­
related
changes
in
mortality,
clinical
signs
of
toxicity,
body
weight,
food
consumption
or
clinical
chemistries.
The
LOAEL
is
1.54%
(
in
males,
268
mg/
kg/
day
test
material
and
32
mg/
kg/
day
boron
equivalents;
in
females,
192
mg/
kg/
day
test
material
and
23
mg/
kg/
day
boron
equivalents),
based
on
decreased
body
weight
gain,
testicular
histopathology
and
slightly
decreased
hematocrit/
hemoglobin.
The
NOAEL
is
0.154%
(
in
males,
35
mg/
kg/
day
test
material
and
4.1
mg/
kg/
day
boron
equivalents;
in
females,
22
mg/
kg/
day
test
material
and
2.6
mg/
kg/
day
boron
equivalents).

This
90­
day
oral
toxicity
study
in
the
dog
is
classified
as
acceptable
(
nonguideline)
and
satisfies
the
guideline
requirement
for
a
90­
day
oral
toxicity
study
(
OPPTS
870.3150;
OECD
409)
in
the
dog
when
considered
together
with
38­
week
and
2­
year
dietary
dog
studies.
This
study
was
not
conducted
according
to
standard
guideline
procedures­
several
clinical
chemistry
parameters
were
not
examined
and
histopathological
examination
was
missing
some
tissues.
However,
the
study
is
considered
to
be
acceptable
for
regulatory
purposes.

Dose
and
Endpoint
for
Risk
Assessment:
8.8
mg/
kg/
day
(
2­
year
study),
based
on
testicular
atrophy
and
slightly
decreased
hematocrit/
hemoglobin
at
32
mg/
kg/
day
(
90­
day
study)

Comments
about
Study/
Endpoint:
The
endpoint
of
concern
was
derived
by
consideration
of
three
dietary
studies
in
the
dog:
a
90­
day,
a
38­
week
and
a
2­
year
study.
A
NOAEL
of
8.8
mg/
kg/
day
was
identified
in
the
2­
year
study
(
HDT).
Clear
effects
on
the
testes
were
seen
at
the
subchronic
LOAEL
of
32
mg/
kg/
day
and
the
38­
week
LOAEL
of
40
mg/
kg/
day;
slight
decreases
in
hematocrit/
hemoglobin
was
also
reported
at
32
mg/
kg/
day
at
90
days
of
treatment.
The
endpoint
is
considered
appropriate
for
the
route
(
oral)
and
durations
(
up
to
one
month
for
short­
term
exposure
and
one
to
six
months
for
intermediate­
term
exposure).
Although
the
exact
onset
of
the
testicular
effects
is
not
Page
36
of
84
known
from
the
available
studies,
it
is
clearly
evident
by
90
days.
It
was
selected
for
the
short­
term
incidental
oral
endpoint
as
well
as
the
intermediate­
term
endpoint
to
ensure
a
protective
exposure
level
due
to
the
uncertainty
regarding
time
of
onset
of
testicular
atrophy.

4.4.3
Dermal
Absorption
Dermal
absorption
data
were
not
submitted
to
the
Agency.
However,
the
available
data
in
experimental
animals
indicate
that
boric
acid
and
sodium
borate
salts
are
not
absorbed
across
intact
or
slightly
abraded
skin,
although
absorption
is
significant
across
severely
damaged
skin.
A
number
of
dermal
absorption
studies
have
been
cited
and
reviewed
in
reviews
on
boron
and
compounds
prepared
by
EPA
IRIS
(
2004),
ATSDR
(
1992)
and
WHO
(
1998).
Nielsen
(
1970,
as
cited
in
IRIS,
2004)
demonstrated
no
absorption
in
rats
with
intact
skin
treated
with
3%
boric
acid
as
aqueous
jelly
or
ointment
and
absorption
of
1%
of
dose
from
oleaginous
ointment
exposure.
In
contrast,
rats
with
severely
damaged
skin
absorbed
up
to
23%
of
the
applied
dose
of
aqueous
boric
acid.
In
another
study,
urinary
boron
was
not
increased
in
rabbits
exposed
dermally
(
intact
or
mildly
abraded
skin)
to
boric
acid
as
undiluted
powder,
5%
in
talc
or
5%
aqueous
solution
(
1.5
hr/
day,
4
days,
exposure
under
occlusion
to
10­
15%
of
body
surface
area).

Data
in
humans
showing
lack
of
absorption
of
boric
acid
across
intact
skin
are
also
available.
A
number
of
studies
are
reviewed
in
the
IRIS
Toxicological
Review
of
Boron
and
Compounds
(
US
EPA
IRIS,
2004).
One
study
(
Draize
and
Kelly,
1959,
MRID
46852201)
showed
no
increase
in
urinary
excretion
of
boron
in
one
human
volunteer
exposed
to
topically
applied
powdered
boric
acid
to
the
forearm
for
four
hours.

4.4.4
Dermal
Exposure
(
Short,
Intermediate
and
Long
Term)

Boric
acid
and
borate
salts
are
not
absorbed
through
the
intact
skin
to
a
significant
extent.
A
dermal
exposure
risk
assessment
is
not
required
at
this
time.

4.4.5
Inhalation
Exposure
(
Short,
Intermediate
and
Long
Term)

Study
Selected:
Chronic
and
subchronic
toxicity
in
the
dog
(
oral)­
three
studies
were
considered
together
to
derive
an
appropriate
endpoint.

MRID
Nos.:
40692307,
40692308,
40692310
Executive
Summaries:
See
Incidental
Oral,
above
(
4.4.2)

Dose
and
Endpoint
for
Risk
Assessment:
Systemic
toxicity
NOAEL
=
8.8
mg/
kg/
day
(
two
year
dog
dietary
study,
MRID
40692310),
based
on
testicular
atrophy
and
slight
decreases
in
hematocrit/
hemoglobin
at
32
mg/
kg/
day
(
90­
day
dog
dietary
study).
Page
37
of
84
Comments
about
Study/
Endpoint:
See
Incidental
Oral,
above
(
4.4.2).
Oral
studies
were
selected
because
there
was
no
inhalation
study
of
appropriate
duration.
The
effects
observed
at
the
selected
endpoint
(
testicular
atrophy)
were
clearly
identified
by
exposure
durations
of
90
days
and
longer,
but
the
time
of
onset
following
initiation
of
exposure
is
not
known.
The
NOAEL
was
selected
to
ensure
adequate
protection
at
all
durations
of
inhalation
exposure,
based
on
the
uncertainty
of
time
to
onset
of
testicular
atrophy.
For
route­
to­
route
extrapolation,
absorption
via
the
inhalation
route
is
assumed
to
be
equivalent
to
oral
absorption.

4.4.6
Margins
of
Exposure
The
target
Margins
of
Exposure
(
MOEs)
for
residential
and
occupational
exposure
and
risk
assessment
are
as
follows:

Route
of
Exposure
Duration
of
Exposure
Short­
Term
(
1­
30
Days)
Intermediate­
Term
(
1­
6
Months)
Long­
Term
(>
6
Months)

Occupational
Exposure
Dermal
100
100
100
Inhalation
100
100
100
Residential
Exposure
Incidental
Oral
100
100
NR
Dermal
NR
NR
NR
Inhalation
100
100
100
NR­
not
required.

The
default
MOE
of
100
was
retained
but
is
considered
a
conservative
value.
Actual
intraspecies/
interspecies
variations
are
likely
to
be
somewhat
lower,
due
to
lack
of
metabolism
of
boric
acid/
sodium
borate
salts,
lack
of
significant
accumulation
in
soft
tissues
and
similarities
in
absorption
and
renal
clearance
of
boron
among
species.
However,
individuals
with
impaired
renal
clearance
may
be
more
sensitive
to
effects
of
boric
acid/
sodium
borate
salts.
Other
reviews
of
boron
or
boric
acid
and
its
salts
by
various
groups
or
Agencies
have
selected
lower
uncertainty
factors,
based
on
toxicokinetic
and
toxicodynamic
considerations.
For
example,
the
US
EPA
IRIS
(
2004)
selected
a
combined
uncertainty
factor
of
66,
WHO
(
1998)
selected
a
combined
uncertainty
factor
of
25,
and
both
the
National
Academy
of
Sciences
Food
and
Nutrition
Board
(
2001)
and
the
European
Centre
for
Ecotoxicology
and
Toxicology
of
Chemicals
(
ECETOC,
1995)
selected
a
combined
uncertainty
factor
of
30.
A
published
risk
assessment
for
drinking
water
exposure
to
humans
proposed
a
combined
uncertainty
factor
of
32
(
Murray,
1995).
Page
38
of
84
4.4.7
Recommendation
for
Aggregate
Exposure
Risk
Assessments
As
per
FQPA
(
1996),
when
there
are
potential
residential
exposures
to
a
pesticide,
an
aggregate
risk
assessment
must
consider
exposures
from
the
three
major
routes:
oral,
dermal
and
inhalation.
Boric
acid
and
its
sodium
salts
are
currently
exempted
from
tolerances,
based
on
what
is
anticipated
to
be
a
relatively
smaller
contribution
anticipated
from
crop
residues
and
drinking
water
runoff
than
the
naturally­
occurring
background
boron
levels.
Dietary
(
food
plus
drinking
water)
risk
assessment
was
therefore
not
performed.
An
aggregate
exposure
risk
assessment
was
not
performed
for
the
reasons
outlined
in
Section
7.0
of
this
document
(
Aggregate
Risk
Assessments
and
Risk
Characterization).

4.4.8
Classification
of
Carcinogenic
Potential
4.4.8.1
Two
Year
Dietary
Study
in
the
Rat
(
1)
In
an
oral
carcinogenicity
study
(
MRID
40692309),
borax
(
sodium
tetraborate
decahydrate
tech.,
103.2­
105.4%
of
theoretical
value)
was
administered
to
70
control
and
35
treated
Sprague­
Dawley
Charles
River
cesarean­
derived
rats/
sex/
dose
in
the
diet
at
dose
levels
of
0
(
control),
0.103%,
0.308%
or
1.03%
(
equivalent
to
0,
65,
154
or
515
mg/
kg/
day
test
material;
0,
7.3,
17
or
58
mg/
kg
bw/
day
for
elemental
boron)
for
two
years.
Interim
sacrifices
of
5
animals/
sex/
dose
were
performed
at
weeks
28
and
56.

At
1.030%,
clinical
signs
attributed
to
treatment
included
dry
scaly
tails,
rough
fur,
hunched
appearance,
wheezing,
bloody
nasal
and
ocular
discharge,
drooping,
inflamed
eyelids,
swollen
paw
pads,
abnormally
long
claws
and
shrunken
scrotum.
Mean
body
weight/
weight
gain
were
reduced
in
both
males
(­
16%/­
19%
below
controls)
and
females(­
33%/­
41%
below
controls),
with
decreases
observed
beginning
in
the
first
weeks
of
treatment.
Significant
reductions
in
absolute
and
relative
testes
weight
at
6,
12
and
24
months'
sacrifice
were
observed.
The
latter
correlated
with
grossly
visible
small
testes,
testicular
tubular
atrophy
(
primarily
severeobserved
in
all
animals
examined
at
6,
12
and
24
months)
and
a
possible
increase
in
testicular
calcific
arteriosclerosis.
Hematocrit
and
hemoglobin
were
slightly
decreased
in
both
sexes
at
several
time
points,
beginning
at
month
2
(
Hct
­
5%
to
­
13%
and
Hgb
­
10
to
­
14%;
sporadic
statistically
significant
changes
seen).
There
were
no
treatment­
related
effects
on
survival
(
control
to
high
dose
males
58%,
76%,
64%
and
72%;
females
67%,
68%,
58%
and
80%),
clinical
chemistry
or
urinalysis
parameters.
The
systemic
toxicity
LOAEL
is
1.03%
(
515
mg/
kg/
day
test
material
and
58
mg/
kg/
day
elemental
boron),
based
on
decreased
body
weight,
clinical
signs
of
toxicity,
decreased
rbc
parameters
and
testicular
pathology.
The
NOAEL
is
0.308%
(
154
mg/
kg/
day
test
material
and
17
mg/
kg/
day
elemental
boron).

At
the
doses
tested,
there
was
not
a
treatment
related
increase
in
tumor
incidence
when
compared
to
controls.
Dosing
was
considered
adequate
based
on
observations
of
clinical
signs,
decreased
body
weight,
slight
hematological
changes
and
testicular
atrophy.
Page
39
of
84
This
carcinogenicity
study
in
the
rat
is
classified
as
acceptable
(
nonguideline)
and
satisfies
the
guideline
requirement
for
a
chronic
toxicity/
carcinogenicity
study
[
OPPTS
870.4200;
OECD
451]
in
rats.
It
is
noted
that
some
clinical
chemistry
parameters
were
not
evaluated
and
that
ophthalmologic
examinations
and
microscopic
examination
of
the
eyes
were
not
performed.
In
addition,
the
percent
survival
of
mid
dose
males
as
presented
in
the
study
report
(
76.9%)
differed
from
calculation
from
the
individual
animal
survival
data
(
64%);
however,
this
discrepancy
has
been
clarified
by
the
registrant
and
64%
is
the
correct
value.

(
2)
In
an
oral
chronic
toxicity/
carcinogenicity
study
(
MRID
00068883),
boric
acid
(
technical,

$
98.7%
a.
i.)
was
administered
in
the
diet
to
35
Sprague
Dawley
rats/
sex/
dose
at
0.067,
0.20
or
0.67%
(
equivalent
to
average
daily
intakes
of
0,
5.2,
16
or
58
mg/
kg/
day,
males
and
0,
6.3,
19
or
70
mg/
kg/
day,
respectively,
females).
In
addition,
control
groups
of
70/
sex
were
administered
untreated
diet.
Interim
sacrifice
groups
(
5/
sex/
dose)
were
evaluated
at
26
and
52
weeks.
Samples
of
blood,
urine
and
feces
were
collected
at
26,
52
and
104
weeks
for
boron
balance
analyses;
select
tissue
samples
were
also
collected
from
5
animals/
sex
at
sacrifice
times
for
boron
analyses.

At
0.67%,
clinical
signs
of
toxicity
beginning
at
4­
6
weeks
(
hunched
posture,
desquamation
of
tail
and
paws,
swollen
paws,
inflamed
eyes,
respiratory
effects
and
shrunken
scrotum),
decreased
mean
body
weights,
low
red
blood
cell
volume
and
hemoglobin
in
males
and
decreased
abs/
rel
testes
weight
and
severe
testicular
atrophy
(
by
26
weeks,
progressing
in
severity
with
time).
In
females,
anovulatory
ovaries
were
observed.
At
104
weeks
control,
low
and
mid
dose
males
also
showed
signs
of
atrophy.
The
incidence
was
not
increased
but
severity
showed
a
slight
increase;
however,
given
the
advanced
age
of
the
rats,
this
was
not
considered
clearly
treatment­
related.
Boron
balance
studies
showed
that
there
was
no
significant
accumulation
in
tissues,
although
levels
of
treated
animals
were
higher
than
controls.
Boron
blood
levels
increased
with
dose.
The
LOAEL
is
0.67%
(
58
mg/
kg/
day
boron
equivalents),
based
on
clinical
signs,
decreased
body
weight,
hematological
changes
in
males,
testicular
atrophy
and
possibly
increased
anovulatory
ovaries.
The
NOAEL
is
0.20%
(
16
mg/
kg/
day
boron
equivalents).

There
was
no
evidence
of
a
treatment­
related
increase
in
tumors.
Dosing
was
considered
adequate
based
on
significant
toxicity
at
the
highest
dose
tested.

This
carcinogenicity
study
in
the
rat
is
classified
as
acceptable
(
nonguideline)
and
satisfies
the
guideline
requirement
for
a
chronic
toxicity/
carcinogenicity
study
[
OPPTS
870.4200;
OECD
451]
in
rats.
It
is
noted
that
some
clinical
chemistry
parameters
were
not
evaluated,
ophthalmologic
examinations
were
not
performed
and
some
tissues
were
not
examined
microscopically.
However,
it
is
considered
an
acceptable
study
for
regulatory
purposes.
Page
40
of
84
4.4.8.2
Two
year
dietary
study
in
the
mouse
In
an
oral
carcinogenicity
study
(
MRID
41863101),
boric
acid
(
technical,
99.7%
a.
i.,
lot
no.
051479)
was
administered
to
50
B6C3F1
mice/
sex/
dose
in
the
diet
at
dose
levels
of
0,
2500
or
5000
ppm
(
equivalent
to
0,
275
or
549
mg/
kg/
day
test
material;
0,
78
or
201
mg/
kg/
day
for
boron
equivalents)
for
two
years.

At
2500
ppm,
slightly
reduced
survival
of
males
was
seen
in
the
last
weeks
of
the
study
(
60%
vs.
82%,
controls);
female
survival
was
unaffected
(
control
to
high
dose
66%,
66%
and
74%).
Splenic
lymphoid
depletion
in
males
(
controls
to
high
dose
5/
48,
11/
49
and
25/
48,
respectively)
was
considered
secondary
to
stress.
At
5000
ppm,
survival
of
males
was
reduced
compared
to
controls
during
the
second
year
of
treatment
(
at
termination,
44%
at
high
dose
vs.
82%,
controls),
although
it
was
noted
that
5
high
dose
males
died
accidentally.
Mean
body
weights
were
decreased
in
males
(­
17%
at
termination)
and
females
(­
20%
at
termination)
beginning
during
months
6­
8.
Increases
in
the
incidence
of
testicular
atrophy
(
control
to
high
dose
3/
49,
6/
50
and
27/
47)
and
interstitial
cell
hyperplasia
(
0/
49,
0/
50
and
7/
47)
were
seen
in
males.
No
treatment­
related
effects
on
clinical
signs
of
toxicity
were
reported.
Clinical
pathology,
hematology,
ophthalmologic
and
organ
weight
data
were
not
collected
in
this
study.
The
LOAEL
in
males
is
2500
ppm
(
275
mg/
kg/
day
test
material;
78
mg/
kg/
day
boron
equivalents),
based
on
increased
mortality
and
splenic
lymphoid
depletion.
A
NOAEL
in
males
was
not
determined
(<
275
mg/
kg/
day
test
material;
78
mg/
kg/
day
boron
equivalents).
The
LOAEL
in
females
is
5000
ppm
(
549
mg/
kg/
day
test
material;
201
mg/
kg/
day
boron
equivalents),
based
on
decreased
body
weight.
The
NOAEL
in
females
is
2500
ppm
(
275
mg/
kg/
day
test
material;
98
mg/
kg/
day
boron
equivalents).

At
the
doses
tested,
there
was
not
a
treatment
related
increase
in
tumor
incidence
when
compared
to
controls.
A
marginal
increase
in
the
incidence
of
hepatocellular
carcinomas
in
low
dose
males
(
control
to
high
dose
overall
rates
5/
50,
12/
50
and
8/
49)
and
combined
hepatocellular
adenomas
and
carcinomas
(
control
to
high
dose
overall
rates
14/
50,
19/
59
and
15/
49)
in
low
dose
males
were
not
considered
treatment­
related
because
they
were
within
historical
control
range
and
not
significant
when
analyzed
by
the
incidental
tumor
test.
An
increase
in
the
combined
incidence
of
subcutaneous
tumors
(
fibromas,
sarcomas,
fibrosarcomas,
neurofibrosarcomas)
in
mid
dose
males
2/
50,
10/
50
and
2/
50)
was
not
considered
treatment­
related
because
of
the
variability
in
spontaneous
occurrence
of
these
tumors
in
historical
controls
and
lack
of
a
dose­
response.
Dosing
was
considered
adequate
in
males
and
females
based
on
findings
of
reduced
survival
of
males
at
mid
and
high
dose,
testicular
atrophy
in
males
at
the
high
dose
and
reduced
body
weights
in
males
and
females
at
the
high
dose
of
5000
ppm.
The
study
report
noted
that
sensitivity
of
the
cancer
assessment
in
males
may
have
been
reduced
due
to
reduced
survival
at
the
high
dose.

This
carcinogenicity
study
in
mice
is
classified
as
acceptable
(
nonguideline)
and
satisfies
the
guideline
requirement
for
a
carcinogenicity
study
[
OPPTS
870.4200;
OECD
451]
in
mice.
Several
study
deficiencies
are
noted
for
this
report,
including
lack
of
clinical
pathology
and
organ
weights
(
liver,
kidney,
tested,
brain).
However,
MTDs
were
achieved
for
both
sexes
and
the
Page
41
of
84
study
is
considered
adequate
for
purposes
of
assessing
the
carcinogenicity
of
boric
acid
in
the
mouse.

Cancer
classification:
Boric
acid
and
borate
salts
may
be
classified
under
the
current
carcinogen
assessment
guidelines
(
US
EPA,
2005)
as
"
not
likely
to
be
carcinogenic
to
humans."
The
HED
RfD
Committee
previously
classified
boric
acid/
borate
salts
as
Group
E­
not
carcinogenic
to
humans
using
the
1986
Agency
cancer
guidelines
(
RfD/
Peer
Review
Report
of
Boric
Acid/
Borax,
HED
Memorandum
dated
11/
24/
93
from
G.
Ghali
to
R.
Forrest
and
L.
Rossi,
dated
November
24,
1993).
Available
genotoxicity
studies
do
not
indicate
mutagenic
potential.
Two­
year
dietary
studies
in
the
rat
and
a
mouse
carcinogenicity
study
did
not
show
clear
evidence
of
increased
cancer
incidence.

Table
4.4.
Summary
of
Toxicological
Doses
and
Endpoints
for
Chemical
for
Use
in
Human
Risk
Assessments­
expressed
in
boron
equivalents
Exposure
Scenario
Dose
Used
in
Risk
Assessment,
UF
Special
FQPA
SF*
and
Level
of
Concern
for
Risk
Assessment
Study
and
Toxicological
Effects
Acute
and
Chronic
Dietary
(
all
populations)
The
contribution
of
boron
residues
from
food/
feed
crop
application
of
boric
acid/
sodium
borate
salts
to
the
total
naturally
occurring
background
dietary
boron
intake
from
food
and
water
is
not
considered
to
be
significant.
Endpoints
for
acute
and
chronic
dietary
exposure
were
not
selected
for
this
risk
assessment
because
it
was
determined
that
a
dietary
risk
assessment
(
food
plus
drinking
water
exposure)
was
not
necessary
at
this
time.

Incidental
Oral
­
all
populations,
all
exposure
durations
(
short­
and
intermediate­
term)
NOAEL
8.8
mg/
kg/
day
Residential
LOC
for
MOE
=
100
Occupational
LOC
for
MOE
=
100
Chronic
and
subchronic
oral
toxicity
in
dogs
(
several
studies
considered
together)

LOAEL
=
32
mg/
kg/
day,
based
on
testicular
atrophy,
slight
hematological
changes
in
subchronic
study
Dermal
­
all
exposure
durations
(
short­,
intermediate­
and
long­
term)
Boric
acid
and
its
sodium
salts
are
not
absorbed
across
intact
skin
and
a
dermal
exposure
assessment
is
not
required.

Inhalation­
all
exposure
durations
(
short­,
intermediate­
and
long­
term)
NOAEL
=
8.8
mg/
kg/
day
(
Assume
inhalation
absorption
=
oral
absorption)
Residential
LOC
for
MOE
=
100
Occupational
LOC
for
MOE
=
100
Chronic
and
subchronic
oral
toxicity
in
dogs
(
several
studies
considered
together)

LOAEL
=
32
mg/
kg/
day,
based
on
testicular
atrophy,
slight
hematological
changes
in
subchronic
study
Cancer
(
oral,
dermal,
inhalation)
Classification:
Not
carcinogenic
to
humans
UF
=
uncertainty
factor,
FQPA
SF
=
Special
FQPA
safety
factor,
NOAEL
=
no
observed
adverse
effect
level,
LOAEL
=
lowest
observed
adverse
effect
level.
*
Refer
to
Section
4.5
Page
42
of
84
4.5
Special
FQPA
Safety
Factor
Based
upon
the
hazard
data
presented
above,
it
is
recommended
that
the
special
FQPA
SF
be
reduced
to
1x
because
there
are
no
residual
uncertainties
with
regard
to
pre­
and/
or
postnatal
toxicity.
The
pre­
and
post­
natal
toxicity
of
boric
acid
and
its
sodium
salts
has
been
adequately
characterized.
Increased
fetal
sensitivity
was
observed
in
the
rat
in
developmental
toxicity
studies,
as
evidenced
by
decreased
fetal
body
weight
and
increased
incidence
of
skeletal
abnormalities
below
maternally
toxic
doses.
Rabbits
and
mice
did
not
demonstrate
increased
fetal
sensitivity.
Reproductive
toxicity
studies
in
two
species
are
also
available.
The
mechanism
of
testicular
effects
(
inhibited
spermiation,
testicular
atrophy)
has
not
been
characterized,
but
the
lack
of
effects
on
male
reproductive
function
in
the
rat
and
mouse
reproductive
toxicity
studies
at
doses
(
NOAELS
25­
26
mg/
kg/
day)
greater
than
the
endpoint
used
for
this
risk
assessment
(
NOAEL
8.8
mg/
kg/
day)
suggests
that
there
is
not
increased
sensitivity
of
the
developing
testes.

Clinical
effects
on
the
nervous
system
in
animal
studies
are
observed
only
at
high
dose
levels.
The
increased
incidence
of
enlarged
fetal
lateral
ventricles
seen
in
the
rat
developmental
toxicity
study
(
MRID
41725401,
42377101)
was
also
observed
at
a
much
higher
dose
level
(
58
mg/
kg/
day,
no
increase
observed
at
14
or
29
mg/
kg/
day)
than
the
most
sensitive
available
LOAEL
for
developmental
toxicity
(
13.3
mg/
kg/
day,
with
a
NOAEL
of
9.6
mg/
kg/
day
in
the
rat,
MRID
43340101).
The
CNS
effect
observed
in
the
rat
study
was
not
observed
in
developmental
toxicity
studies
in
two
other
species
(
mouse
and
rabbit)
at
comparable
or
higher
doses.
The
endpoint
selected
for
the
various
exposure
scenarios
in
this
risk
assessment
is
the
most
sensitive
NOAEL
(
8.8
mg/
kg/
day
based
on
testicular
atrophy)
and
is
therefore
considered
adequately
protective
of
the
fetus
for
developmental
effects
on
the
nervous
system.

4.6
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).

The
potential
for
disruption
of
the
endocrine
system
by
boric
acid/
sodium
borate
salts
is
Page
43
of
84
not
known
at
this
time.
Boric
acid
and
sodium
borate
salts
are
known
to
inhibit
spermiation
in
multiple
species.
Studies
indicate
that
at
high
dose
levels,
boric
acid
causes
a
mild
reduction
in
basal
serum
testosterone
levels
in
male
rats
and
that
this
effect
may
be
CNS­
mediated,
based
on
lack
of
apparent
effects
on
steroidogenic
function
on
isolated
Leydig
cells
(
Ku
and
Chapin,
1994a).
At
this
time,
Fail
et
al.
(
1998)
have
noted
that
boron
is
unlikely
to
act
as
an
endocrine
disruptor
because
the
hormonal
changes
appear
to
be
secondary
to
testicular
cytotoxicity.
However,
the
mechanism
by
which
inhibition
of
spermiation,
as
well
as
effects
on
the
ovary,
occur
in
vivo
have
not
been
fully
characterized.
When
the
appropriate
screening
and/
or
testing
protocols
being
considered
under
the
EDSP
have
been
developed,
boric
acid/
sodium
borate
salts
may
be
subject
to
additional
screening
and/
or
testing.

5.0
Public
Health
Data
5.1
Incident
Reports
Incident
reporting
data
and
case
reports
of
human
toxicity
have
been
reviewed
by
HED
(
memorandum
from
Monica
Hawkins
and
Hans
Allender
to
Linnea
Hansen,
DP
Barcode
DP320914).
The
following
databases
were
reviewed
and
findings
are
summarized
for
each:

1)
OPP
Incident
Data
System
(
IDS)
­
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
documentation
risk
mitigation
measures
may
be
suggested.

Findings:
Twenty
incident
cases
for
boric
acid
or
sodium
borate
salts
were
reported
to
OPP
since
1992.
Of
these,
about
one­
half
were
reportedly
due
to
inhalation
exposure
either
during
application
or
postapplication.
Some
cases
appeared
to
be
due
to
misapplication
of
products;
other
reports
did
not
contain
sufficient
information
to
make
that
determination.
Symptoms
commonly
reported
included
headache,
nausea,
vomiting,
rash,
respiratory
irritation/
shortness
of
breath,
coughing,
chest
pain,
ocular
irritation
and
diarrhea.

2)
Poison
Control
Centers
­
as
the
result
of
a
data
purchase
by
EPA,
OPP
received
Poison
Control
Center
data
covering
the
years
1993
through
1998
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.

Findings:
Comparisons
were
made
between
boric
acid­
related
products
and
all
pesticides
cases
reported
for
percent
cases
with
symptomatic
outcomes
and
degree
of
severity
of
the
outcome,
and
the
percent
resulting
in
a
visit
to
a
health
care
facility
and
of
those,
the
percentage
Page
44
of
84
resulting
in
hospitalization
or
requiring
intensive
care.
Separate
comparisons
were
made
for
occupational
cases,
non­
occupational
cases
for
adults
and
older
children
and
non­
occupational
cases
for
children
under
six
years
of
age.
The
largest
number
of
exposures
was
reported
in
children
under
six
(
total
26,993),
followed
by
non­
occupational
adult/
older
child
(
4,231)
and
occupational
exposures
to
adults
(
93).
Comparisons
of
the
data
indicated
that
relative
to
all
pesticides,
boric
acid­
related
products
were
in
general
less
likely
to
result
in
symptomatic
outcomes
of
any
severities,
or
to
require
medical
care.
Occupational
cases
for
boric
acid­
related
products
were
more
likely
than
the
non­
occupational
cases
to
result
in
a
symptomatic
outcome,
or
an
outcome
with
moderate
to
severe
effects.
The
incidence
of
moderate
to
severe
outcomes
was
relatively
low
for
all
groups
(
9.8%,
occupational,
4.11%,
non­
occupational
adult/
older
child
and
0.26%,
children
under
six)
and
outcomes
that
were
life­
threatening
or
fatal
were
rare
(
one
reported
among
children
under
six).
The
most
common
findings
reported
among
the
symptomatic
outcomes
were
vomiting,
eye
irritation,
nausea
and
oral
irritation;
these
symptoms
were
observed
among
a
relatively
small
percentage
of
the
total
exposures.

3)
California
Department
of
Pesticide
Regulation
­
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.

Findings:
Since
1982,
80
cases
of
illness
judged
as
definitely,
probably
or
possibly
related
to
boric
acid
compounds
alone
were
identified.
The
majority
reported
systemic
effects,
but
respiratory,
skin
and
eye
effects
were
also
commonly
seen.
Usually
there
were
from
one
to
five
incidents
per
year,
but
in
a
few
years
more
were
observed.
These
were
due
to
two
separate
incidents
of
multiple
persons
being
exposed
at
a
workplace
following
misapplication
of
boric
acid.
Exposures
of
applicators
to
excessive
amounts
of
boric
acid
accounted
for
21%
of
the
reported
incidents.
Systemic
effects
reported
included
headache,
difficulty
breathing,
sore
throat,
chemical
pneumonitis
and
diarrhea.

4)
National
Pesticide
Information
Center
(
NPIC)
­
NPIC
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.

Findings:
On
the
list
of
the
top
200
chemicals
for
which
NPIC
received
calls
from
1984­
1991
inclusively,
boric
acid
was
ranked
25th
with
142
incidents
in
humans
reported
and
48
in
animals
(
mostly
pets).

5)
National
Institute
of
Occupational
Safety
and
Health's
Sentinel
Event
Notification
System
for
Page
45
of
84
Occupational
Risks
(
NIOSH
SENSOR)
performs
standardized
surveillance
in
seven
states
from
1998
through
2002.
States
included
in
this
reporting
system
are
Arizona,
California,
Florida,
Louisiana,
Michigan,
New
York,
Oregon,
Texas,
and
Washington.
Reporting
is
very
uneven
from
state
to
state
because
of
the
varying
cooperation
from
different
sources
of
reporting
(
e.
g.,
workers
compensation,
Poison
Control
Centers,
emergency
departments
and
hospitals,
enforcement
investigations,
private
physicians,
etc.).
Therefore,
these
reports
should
not
be
characterized
as
estimating
the
total
magnitude
of
poisoning.
The
focus
is
on
occupationallyrelated
cases
not
residential
or
other
non­
occupational
exposures.
However,
the
information
collected
on
each
case
is
standardized
and
categorized
according
to
the
certainty
of
the
information
collected
and
the
severity
of
the
case.

Findings:
A
total
of
26
cases
were
reported
from
occupational
exposure,
primarily
to
boric
acid
and
some
to
sodium
borate
salts
(
out
of
a
total
of
5,899
reported
exposure
cases
from
1998­
2002).
One
case
classified
as
of
major
severity
resulted
from
ingestion
of
boric
acid;
this
man
reported
diarrhea,
vomiting,
muscle
weakness,
blurred
vision,
salivation,
tremors,
tachycardia
and
miosis.
The
remaining
cases
were
of
moderate
severity
(
10)
or
minor
severity
(
15)
and
clinical
symptoms
included
headache,
diarrhea,
vomiting,
coughing,
upper
respiratory
pain/
irritation,
dyspnea
and/
or
conjunctivitis.

In
summary,
reviews
of
Poison
Control
Center
data
support
a
finding
that
routine,
inadvertent
exposures
among
infants
and
small
children
to
boric
acid
seldom
pose
a
significant
risk.
However,
ingestions
of
substantial
amounts
pose
serious
risks.
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.

5.2
Other
The
memo
cited
above
(
Hawkins
and
Allender)
also
discussed
case
reports
of
poisonings
from
the
literature.
Case
reports
of
toxicity
and
mortality
among
infants
exposed
dermally
(
to
treat
diaper
rash)
or
orally
(
usually
by
accident)
have
been
published.
Two
reports
of
borate
toxicity
in
infants
have
been
published
in
which
a
honey­
borax
mixture
was
applied
to
infant
pacifiers,
resulting
in
seizures
and
other
effects
after
several
weeks
of
exposure.
Application
to
skin
from
former
uses
as
an
antiseptic
has
resulted
in
skin
effects
and
systemic
poisoning.

Human
epidemiology
and
case
report
data
were
summarized
in
the
US
EPA
IRIS
Toxicological
Review
of
Boron
(
2004).
Oral
and
inhalation
exposures
were
evaluated.
Several
studies
were
available
evaluating
respiratory
and
reproductive
effects
on
workers
exposed
occupationally
to
dusts
of
boric
acid
and
boron
salts
were
evaluated
in
facilities
in
Russia
and
the
United
States.
The
studies
were
not
considered
adequate
to
assess
reproductive
effects.
However,
respiratory
toxicity
(
irritation,
chronic
bronchitis)
and
eye
irritation
was
associated
with
exposure
to
high
airborne
levels
of
boric
acid
or
borate
dusts.
Page
46
of
84
6.0
Exposure
Characterization/
Assessment
6.1
Dietary
Exposure/
Risk
Pathway
A
dietary
exposure
risk
assessment
was
not
performed
for
boric
acid
and
sodium
borate
salts.
Tolerance
exemptions
were
granted
for
boric
acid
and
its
sodium
salts
based
on
low
residue
levels
of
boron
from
their
use
relative
to
the
naturally
occurring
boron
levels
in
plants
(
CFR
180.1121).
Estimates
of
human
daily
dietary
intake
of
boron
from
food
and
water
sources
in
the
United
States
range
from
0.26
to
7.1
mg/
day,
with
a
mean
of
1.9
mg/
day,
equivalent
to
about
0.03
mg/
kg/
day
in
adults
(
Moore,
1997).
Other
survey
data
indicate
average
daily
dietary
boron
intakes
of
0.5
to
3.1
mg/
day
(
0.007
to
0.044
mg/
kg/
day)(
Nielsen,
1991).
The
FDA
determined
an
average
U.
S.
adult
male
dietary
boron
intake
of
1.52
mg/
day
(
0.025
mg/
kg/
day)(
Iyengar
et
al.,
1988).
In
general,
a
vegetarian
diet
would
provide
a
higher
daily
intake
than
an
omnivorous
diet
(
Rainey
et
al.,
1999).
Some
dietary
supplements
also
contain
trace
levels
of
boron.

6.2
Water
Exposure/
Risk
Pathway
A
risk
assessment
for
drinking
water
exposure
to
boron
from
current
agricultural
uses
is
not
required
at
this
time.
Boron
is
a
naturally
occurring
element
found
in
water.
Estimates
for
typical
fresh
water
boron
concentrations
are
about
<
0.010
to
1.5
ppm.
The
US
EPA
has
not
set
an
MCL
for
boron,
but
in
Canada,
British
Columbia
and
Saskatchewan
have
set
interim
maximum
acceptable
boron
concentrations
of
5.0
mg/
L.
EFED
has
reviewed
the
water
and
label
information
for
the
agricultural
uses
of
boron
compounds.
Based
on
the
low
application
rates
for
agricultural
uses,
the
contribution
to
total
boron
levels
is
not
expected
to
make
a
significant
contribution
to
drinking
water
sources
(
email
memorandum
from
William
Eckel,
EFED,
to
Louis
Scarano
dated
7/
18/
05).
Background
drinking
water
exposures
were
not
included
in
this
risk
assessment
based
on
the
assumption
that
there
is
also
background
exposure
from
drinking
water
to
the
laboratory
animals
used
in
toxicology
studies
on
boric
acid/
sodium
borate
salts.

6.3.2
Other
(
Spray
Drift,
etc.)

Spray
drift
is
always
a
potential
source
of
exposure
to
residents
nearby
to
spraying
operations.
This
is
particularly
the
case
with
aerial
application
(
there
are
currently
no
aerial
applications
for
boric
acid
or
sodium
borate
salts),
but,
to
a
lesser
extent,
could
also
be
a
potential
source
of
exposure
from
the
ground
application
method
employed
for
boric
acid
and
sodium
borate
salts.
The
Agency
has
been
working
with
the
Spray
Drift
Task
Force,
EPA
Regional
Offices
and
State
Lead
Agencies
for
pesticide
regulation
and
other
parties
to
develop
the
best
spray
drift
management
practices.
On
a
chemical
by
chemical
basis,
the
Agency
is
now
requiring
interim
mitigation
measures
for
aerial
applications
that
must
be
placed
on
product
labels/
labeling.
The
Agency
has
completed
its
evaluation
of
the
new
data
base
submitted
by
the
Spray
Drift
Task
Force,
a
membership
of
U.
S.
pesticide
registrants,
and
is
developing
a
policy
on
how
to
appropriately
apply
the
data
and
the
AgDRIFT
computer
model
to
its
risk
assessments
for
Page
47
of
84
pesticides
applied
by
air,
orchard
airblast
and
ground
hydraulic
methods.
After
the
policy
is
in
place,
the
Agency
may
impose
further
refinements
in
spray
drift
management
practices
to
reduce
off­
target
drift
with
specific
products
with
significant
risks
associated
with
drift.

6.3
Residential
(
Non­
Occupational)
Exposure/
Risk
Pathway
Because
this
risk
assessment
is
being
conducted
for
a
tolerance
reassessment,
only
residential
handler
and
residential
and
aquatic
nonfood
residential
(
swimming
pool)
postapplication
exposure
scenarios
are
considered.
In
addition,
potential
exposures
from
household
(
nonpesticidal)
products
containing
boric
acid/
borate
sodium
salts
are
evaluated.
Finally,
residential
postapplication
exposure
to
boric
acid/
sodium
salts
as
inert
ingredients
is
also
assessed.

6.3.1
Home
Uses
Four
categories
of
residential
use
exposure
have
been
assessed:
(
1)
inhalation
exposure
to
residential
handlers;
(
2)
postapplication
incidental
oral
exposure
(
hand­
to­
mouth
transfer)
to
young
children
from
the
use
of
wood
treatment
products
(
pressure
treatment
and
in
situ
treatment),
crack/
crevice
and
broadcast
carpet
treatments;
(
4)
inadvertent,
non­
dietary
postapplication
ingestion
of
swimming
pool
water
treated
with
products
containing
boric
acid
as
an
active
ingredient
or
an
inert
and
(
4)
handler
inhalation
exposure
to
non­
pesticidal
consumer
products
containing
boric
acid
or
borax.

6.3.1.1
Residential
Handler
Exposure
Scenarios
Residential
handler
inhalation
exposure
and
risks
from
products
containing
boric
acid
or
sodium
borate
salts
as
active
pesticidal
ingredients
are
presented
below
in
Table
6.3a.
Details
regarding
product
formulations
and
applications
are
included
in
the
table.

The
exposure
scenarios
chosen
for
this
risk
assessment
were
based
on
the
anticipated
use
patterns
and
current
labeling
for
products
containing
boric
acid
and
its
sodium
salts
(
see
Table
4.4).
In
addition,
application
rates
were
estimated
based
on
information
provided
on
the
product
labels
and
these
assumptions
are
listed
in
Table
6.3a.
The
average
body
weight
of
an
adult
(
70
kg)
was
assumed.
The
oral
NOAEL
of
8.8
mg
boron/
kg­
day
was
used
for
both
the
short­
and
intermediate­
term
inhalation
exposure
estimates
since
there
are
no
inhalation
toxicological
studies
available.
An
uncertainty
factor
of
100
(
10
for
interspecies
extrapolation
and
10
for
intraspecies
variation)
was
selected
for
this
assessment
and
therefore,
a
Margin
of
Exposure
(
MOE)
of
100
is
required
for
residential
exposure
risk
assessment.
Calculated
inhalation
handler
MOEs
ranged
from
a
low
of
800
for
mixing,
loading
and
applying
dusts
containing
boric
acid
via
a
shaker
can
to
a
high
of
5,600,000
for
the
application
of
pour­
on
ready­
to­
use
formulations
containing
sodium
tetraborate
pentahydrate.
More
detailed
information,
such
as
the
inhalation
unit
exposure
and
dose
calculations,
is
provided
in
Appendix
3.0.
Page
48
of
84
Table
6.3a
Residential
Handler
Inhalation
Risks
Due
to
Exposure
to
Boric
Acid
and
its
Sodium
Salts
as
Active
Ingredients
Registration
Number
Exposure
Scenario
Percent
active
ingredient
Assumptions
for
estimating
product
application
rate
Calculations
of
product
application
rate
(
AR)
Application
Rate
Units
Area
Treated
or
Amount
Handled
Dailya
Units
Baseline
Inhalation
MOEb
BORIC
ACID
9444­
150
Applying
Ready
to
Use
Formulations
with
Aerosol
Cans
20
Used
1.51
g/
mL
as
density
=
2.51
lb
ai/
gal;
assume
use
1
14­
oz
can
per
event
AR
=
(
1.51
g/
mL)*(
1000
mL/
L)*(
3.785
L/
gal)*(
1
kg/
1000
g)*(
2.2
lb/
1
kg)*(
20/
100)*(
0.0078
gal/
oz)*
14
oz
(
mass)
0.17
lb
ai/
day
NA
NA
8,800
70908­
3
Mixing/
Loading/

Applying
Dusts
via
Shaker
Can
100
From
label,
apply
1
lb/
50
ft2
for
flea
control
on
carpets
AR
=
1
lb/
50ft2
0.02
lb
ai/
ft2
256c
ft2/
day
800
1677­
191
Granular
Bait
Dispersed
by
Hand
54
Used
1.51
g/
mL
as
density
=
2.51
lb
ai/
gal;
assume
apply
½
container
(
6
oz)
AR
=
(
1.51
g/
mL)*(
1000
mL/
L)*(
3.785
L/
gal)*(
1
kg/
1000
g)*(
2.2
lb/
1
kg)*(
54/
100)*(
0.0078
gal/
oz)*
6
oz
0.2
lb
ai/
day
NA
NA
38,000
SODIUM
TETRABORATE
DECAHYDRATE
48369­
2
Mixing/
Loading/

Applying
Dusts
via
Shaker
Can
100
From
label:

package
is
1
lb;

assume
use
½
(
0.5
lb)
and
since
percent
a.
i.
is
100,

assume
0.5
lb
a.
i.
AR
=
0.5
lb
ai/
day
0.5
lb
ai/
day
NA
NA
13,000
SODIUM
TETRABORATE
PENTAHYDRATE
5185­
461
Loading/
Applying
Granulars
via
Spoon
or
Cup
100
From
label,
apply
4.5
lbs/
1000
gal;

assume
treat
20,000
gal/
day
AR
=
(
4.5
lb/
1000
gal)
0.0045
lb
ai/
gal
20000
gal/
day
1,000
5185­
492
Applying
Ready
to
Use
Formulations
via
Pour­
on
100
From
label,
apply
10
oz/
200
gal;

assume
treat
200
gal/
day
AR
=
(
10
oz)*(
0.0625
lb/
1
oz)/(
200
gal)
0.0031
lb
ai/
gal
200
gal/
day
5,600,000
SODIUM
TETRAHYDRATE
Table
6.3a
Residential
Handler
Inhalation
Risks
Due
to
Exposure
to
Boric
Acid
and
its
Sodium
Salts
as
Active
Ingredients
Registration
Number
Exposure
Scenario
Percent
active
ingredient
Assumptions
for
estimating
product
application
rate
Calculations
of
product
application
rate
(
AR)
Application
Rate
Units
Area
Treated
or
Amount
Handled
Dailya
Units
Baseline
Inhalation
MOEb
Page
49
of
84
1083­
1
Applying
Ready
to
Use
Formulations
via
Trigger­
Pump
Sprayer
0.28
Use
density
(
2.56
g/
mL)
to
determine
lb
ai/
gal;
assume
apply
1
pint
of
solution
(
0.125
gal/
day)
AR
=
(
2.56
g/
mL)*(
1000
mL/
L)*(
3.785
L/
gal)*(
1
kg/
1000
g)*(
2.2
lb/
kg)*(
0.28/
100)
0.06
lb
ai/
gal
0.125
gal/
day
3,100,000
DISODIUM
OCTABORATE
71653­
5
Mixing/
Loading/

Applying
Emulsifiable
Concentrates
with
a
Paint
Brush
18.12
Use
density
(
1.8
g/
mL)
to
determine
lb
ai/
gal;
assume
apply
1
liter
of
solution
(
0.264
gal/
day)
AR
=
(
1.8
g/
mL)(*
1000
mL/
L)*(
3.785
L/
gal)*(
1
kg/
1000
g)(*
2.2
lb/
kg)*(
18.12/
100)
2.72
lb
ai/
gal
0.264
gal/
day
12,000
DISODIUM
OCTABORATE
TETRAHYDRATE
64405­
6
Applying
Ready
to
Use
Formulations
via
Trigger­
Pump
Sprayer
8.5
Use
density
(
0.32
g/
mL)
to
determine
lb
ai/
gal;

assume
apply
1
gal/
day
AR
=
(
0.32
g/
mL)*(
1000
mL/
L)*(
3.785
L/
gal)*(
1
kg/
1000
g)*(
2.2
lb/
kg)*(
8.5/
100)
0.23
lb
ai/
gal
1
gal/
day
100,000
72468­
2
Applying
dilute
sprays
to
decks
using
low
pressure
handwand
10
10%
DOT
=
1
lb
ai/
gal/
200
sq
ft
DOT
=
20.96%

Boron
1
lb
ai
*
20%
boron
=
0.21
lb
boron
applied
0.21
lb/
gal
/
200
sq
ft
lb
ai/
gal
10
gal/
day
98,000
79628­
1
Mixing/
Loading/

Applying
Emulsifiable
Concentrates
with
a
Paint
Brush
99.98
From
label,
apply
1
lb/
gallon
solution;

apply
10
gallons/
day
NA
1
lb
ai/
gal
10
gal/
day
1,000
79628­
1
Mixing/
Loading/
Ap
plying
Emulsifiable
Concentrates
with
Low
Pressure
Handwand
99.98
From
label,
apply
1
lb/
gallon
solution;

apply
10
gallons/
day
NA
1
lb
ai/
gal
10
gal/
day
9,700
a
Amount
handled
per
day
values
are
either
determined
from
the
product
label
or
are
EPA
estimates
of
amount
treated
based
on
revised
Residential
SOPs
(
2/
01).
Page
50
of
84
b
Baseline
Inhalation
MOE
=
NOAEL
(
8.8
mg
boron/
kg­
day)
/
adjusted
inhalation
daily
dose
(
mg/
kg­
day),
where
adjusted
inhalation
dose
=[
daily
unit
exposure
(
µ
g/
lb
ai)
x
application
rate
x
amount
handled
per
day
x
conversion
factor
(
if
needed)
/
body
weight
(
70
kg
adult)]
*
percent
boron.
c
Assume
area
of
average
household
room
=
256
ft2.

Residential
handler
exposures
to
consumer
use
(
non­
pesticidal)
products
containing
boric
acid
and
sodium
borate
salts
are
shown
below
in
Table
6.3b.
The
Consumer
Exposure
Module
(
CEM)
(
Versar,
1999)
was
used
to
determine
the
lifetime
average
daily
dose
(
LADD),
average
daily
dose
(
ADD)
and
acute
potential
daily
dose
rate
(
ADR).
The
CEM
is
similar
to
the
Agency's
MCCEM
(
multiple
chamber
concentration
and
exposure
model).
A
link
providing
additional
details
on
CEM
is
found
at:
http://
www.
epa.
gov/
opptintr/
exposure/
docs/
efastman.
pdf.
Two
sodium
salts
of
boric
acid
are
known
to
be
ingredients
in
consumer
use
products:
sodium
tetraborate
decahydrate
in
laundry
detergent
and
general
purpose
cleaners
and
sodium
tetraborate
in
laundry
detergent.
The
exposure
scenarios
examined
were
the
use
of
a
general
purpose
cleaner,
assuming
a
weight
fraction
range
of
7%
to
13%,
and
laundry
detergent,
assuming
a
weight
fraction
range
of
1%
to
5%.
Table
6.3b
provides
the
CEM
inhalation
MOE
estimates.
Exposure
output
information
from
the
CEM
model
is
provided
in
Appendix
4.0.
Using
the
oral
NOAEL
of
8.8
mg
boron/
kg­
day
and
assuming
100%
inhalation
absorption,
the
inhalation
MOEs
ranged
from
400,000
for
a
general
purpose
cleaner
containing
sodium
tetraborate
decahydrate
to
13,000,000
for
a
laundry
detergent
containing
sodium
tetraborate.
A
MOE
of
16,000
was
obtained
for
general
purpose
cleaner
with
boric
acid
as
an
inert
ingredient.
Page
51
of
84
Table
6.3b
Summary
of
Consumer
Inhalation
Exposure
Scenario
Weight
Fractions
Years
of
Use
Surface
Area/
Body
Weight
Ratio
(
cm2/
kg)
Frequency
of
Use
(
events/
yr)
Acute
Dose
Rate
(
mg/
kg­
day)
Percent
boron
(%)
Adjusted
Acute
Dose
Rate
(
mg/
kg­
day)
Inhalation
MOEa
SODIUM
TETRABORATE
DECAHYDRATE
(
Active
ingredient)

General
Purpose
Cleaner
0.07­
0.13
57
15.6
300
1.91e­
04
11.34
2.2e­
05
400,000
Laundry
Detergent
0.01­
0.05
57
15.6
312
5.96e­
06
11.34
6.8e­
07
13,000,000
SODIUM
TETRABORATE
(
Active
ingredient)

Laundry
Detergent
0.01­
0.05
57
15.6
312
3.23e­
06
21.49
6.9e­
07
13,000,000
BORIC
ACID
(
Inert
Ingredient)

General
Purpose
Cleaner
0.15
57
15.6
300
3.1e­
03
17.5
5.0e­
04
16,000
a
MOE
=
NOAEL
(
8.8
mg
boron/
kg­
day)/
Adjusted
Acute
Dose
Rate
6.3.1.2
Residential
Postapplication
Exposure
Scenarios
­
Swimming
Pool
Incidental
Oral
Postapplication
incidental
oral
exposure
to
adults
and
children
may
be
anticipated
from
swallowing
swimming
pool
water.
Exposure
characterization
of
postapplication
exposure
to
adult
and
children
swimmers
is
shown
below
in
Table
6.3c.
Two
products
containing
sodium
tetraborate
pentahydrate
may
be
applied
to
both
swimming
pools
and
spas.
In
order
to
assess
exposures,
the
SWIMODEL
(
Version
2.0)
Swimming
Screening
Tool
was
used
(
Versar,
2001).
Oral
exposure
routes
were
examined
for
adults
and
children.
Body
weights
of
70
kg,
30
kg
and
48
kg
were
used
for
adults,
children
(
7­
10
years)
and
children
(
11­
14
years)
respectively.
The
daily
exposures
were
compared
to
the
oral
NOAEL
of
8.8
mg
boron/
kg­
day
to
estimate
a
level
of
risk
(
MOE)
for
both
adults
and
children
(
assessed
separately
for
ages
7­
10
and
11­
14).
Ingestion
rates
of
0.025
liters
per
hour
was
used
for
adults
and
0.05
liters
per
hour
were
used
for
children
(
both
age
groups).
An
hour
of
swimming
was
assumed
for
children
based
on
the
recommendations
in
the
draft
Children's
Exposure
Factors
Handbook.
Table
6.3c
provides
the
SWIMODEL
oral
and
inhalation
MOE
estimates.
For
the
540
mg/
L
concentration,
the
MOEs
Page
52
of
84
for
incidental
oral
exposure
were
65
for
children
7­
10
and
110
for
children
age
11­
14
for
products
containing
sodium
tetraborate
pentahydrate.
For
the
480
mg/
L
concentration,
the
MOEs
for
incidental
oral
exposure
were
74
for
children
7­
10
and
120
for
children
age
11­
14
for
products
containing
sodium
tetraborate
pentahydrate.
For
the
240
mg/
L
concentration
all
MOEs
were
greater
than
100.
MOEs
for
the
inert
uses
were
greater
than
5000
for
children
(
both
age
groups).
The
MOE
for
adults
were
calculated
for
boric
acid
based
on
high
MOEs
in
children.

Table
6.3c.
Postapplication
Exposure
to
Swimmers
Scenario
Exposed
Swimmer
Chemical
concentration
in
water
(
mg/
L)
ADDa
(
mg/
kg/
day)
Percent
boron
Adjusted
ADD
(
mg/
kg/
day)
MOEb
SODIUM
TETRABORATE
PENTAHYDRATE
(
Active
ingredient)

Oral
exposure
Adult
non­
competitive
male
540
0.19
14.85
0.029
310
Child
(
7­
10)
non­
competitive
0.9
14.85
0.134
65
Child
(
11­
14)
non­
competitive
0.56
14.85
0.084
110
Adult
non­
competitive
male
480
0.17
14.85
0.025
345
Child
(
7­
10)
non­
competitive
0.8
14.85
0.119
74
Child
(
11­
14)
non­
competitive
0.5
14.85
0.074
120
Adult
non­
competitive
male
240
0.08
14.85
0.0127
690
Child
(
7­
10)
non­
competitive
0.4
14.85
0.059
150
Child
(
11­
14)
non­
competitive
0.25
14.85
0.037
240
BORIC
ACID
(
Inert
Ingredient)

Oral
exposure
Child
(
7­
10)
non­
competitive
5.4
0.009
17.5
0.0016
5,600
Child
(
11­
14)
non­
competitive
0.0056
17.5
0.001
8,800
a
Oral
exposure
ADD
(
mg/
kg/
day)
=
(
Cw
or
Chemical
concentration
in
water,
µ
g/
L)(
Exposure
time,
hr/
event)*(
Ingestion
rate,
L/
hr)*(
Exposure
frequency,
events/
hr)*(
Exposure
duration,
hrs)*(
conversion
factor,
mg/
µ
g)/(
Body
weight,
kg).
b
NOAEL
of
8.8
mg­
boron/
kg­
day
was
used.
Note:
Adult
MOE
not
shown
for
boric
acid
as
an
inert
since
Children
MOEs
are
above
5,000.

6.3.1.3
Residential
Postapplication
Exposure
Scenarios
­
Children
Hand­
to­
Mouth
Transfer
Postapplication
incidental
oral
exposure
to
boric
acid
and
its
sodium
salts
in
dust
and
ready­
to­
use
liquid
pesticide
products
via
hand­
to­
mouth
transfer
in
young
children
is
anticipated
to
occur
from
contact
with
treated
indoor
surfaces,
such
as
carpets
and
hard
surfaces,
and
on
treated
decks.
Although
the
endpoint
selected
is
for
all
durations,
a
short­
term
exposure
Page
53
of
84
assessment
was
conducted
for
children
because
it
is
the
more
conservative
assessment.

There
are
several
boron
containing
compounds
having
label
directions
for
making
indoor
broadcast
or
crack
and
crevice
applications.
These
include
boric
acid
(
broadcast,
crack
and
crevice
­
dust),
sodium
tetraborate
decahydrate
(
crack
and
crevice
­
dust),
disodium
octaborate
tetrahydrate
(
broadcast
­
spray)
and
disodium
octaborate
(
broadcast
­
spray).
Although
there
are
no
data
submitted
to
the
Agency
addressing
these
uses,
the
Agency
notes
that
an
exposure
assessment
involving
a
broadcast
dust
treatment
to
carpets
had
been
conducted
by
the
California
Department
of
Pesticide
Regulation
(
CDPR).
In
the
exposure
assessment
(
CDPR,
1996),
dislodgeable
surface
residue
measurements
following
a
broadcast
dust
application
had
been
made.
A
mean
of
0.489
µ
g/
cm2
(
boron)
was
measured
from
12
carpet
samples
treated
with
a
64%
orthoboric
acid
compound
applied
at
a
rate
of
3
pounds
per
100
square
feet.
These
data
are
useful
to
estimate
potential
exposure
to
other
boron
containing
compounds
with
several
caveats:
(
1)
The
application
is
comparable
to
broadcast
applications
of
dust
formulations
of
boric
acid;
(
2)
Dust
formulations
are
considered
to
have
higher
dislodgeable
residues
than
spray
formulations;
(
3)
The
sprayable
formulations
of
DOT
and
DO
have
lower
application
rates
than
the
rate
used
in
the
study.
The
application
and
exposure
assumptions
shown
in
Table
6.3d
are
considered
to
represent
worst­
case
scenarios
for
these
use
patterns.
Confirmatory
data
are
being
required.

For
wood
treatment
uses
two
methods
of
wood
treatment
were
assessed;
pressure
treatment
and
in
situ
wood
treatment.
Estimates
of
the
surface
availability
of
boron
are
based
on
the
American
Wood­
Preservers'
Association
(
AWPA)
penetration
standards
for
aqueous
based
or
waterborne
preservatives.
For
disodium
octaborate
tetrahydrate
(
DOT)
uses
(
Formosan
and
non
Formosan
species
of
termites),
retention
depths
of
0.4
inches
(
non
Formosan)
and
0.6
inches
(
Formosan),
coupled
with
chemical
retentions
(
lbs/
ft3)
of
0.25
(
non
Formosan)
and
0.43
(
Formosan)
are
required.
By
using
the
minimum
retention
standard,
an
estimated
surface
availability
of
75%
can
be
made.
The
dislodgeability
of
boron
from
pressure
treated
lumber
and
in
situ
treated
lumber
are
based
on
a
discussion
of
data
presented
in
a
paper
presented
by
Lake
and
McIntyre
(
2006)
and
J.
Lloyd
(
1996)
respectively.
Data
discussed
in
these
presentations
will
need
to
be
submitted
and
reviewed
by
the
Agency
and
will
be
considered
confirmatory.
Page
54
of
84
Table
6.3d.
Summary
of
Representative
Postapplication
Exposures
for
Young
Children
­
Hand
to
Mouth
Transfer
from
Treated
Surfaces
Formulation
Application
Rate
Dislodgeable
Surface
Residue
(
µ
g/
cm2)
Boron
Surface
Area
Mouthed
(
cm2)
Hand
to
Mouth
(
events/
hr)
Extraction
by
Saliva
Exposure
Time
(
hours)
Body
Weight
(
kg)
Average
Daily
Dose
(
mg/
kg­
day
MOEf
Indoor
Carpet
and
Crack
and
Crevice
Uses
Dust
Carpeta
0.02
lb
ai/
sq
ft
0.498
20
20
50%
8
15
0.05
170
Crack
and
Crevice
Dust
Carpet
a,
b
0.02
lb
ai
/
sq
ft
0.249
20
20
50%
8
15
0.03
330
Treated
Wood
(
pressure
and
deck
sprays
(
in
situ))

Pressure
Treated
Woodc
10,340
µ
g
boron/
sq
ft
1.1d
20
20
50%
1
15
0.015
590
Deck
Spray
(
in
situ)
c
462,470
µ
g
boron/
sq
ft
3.73e
20
20
50%
1
15
0.05
180
a
CDPR
Memorandum
(
HSM­
96004);
From
T.
Formoli,
Worker
Health
and
Safety
Branch
to
Karen
Fletcher,
Pesticide
Registration
Branch;
Re:
Evaluation
of
Human
Exposure
Potential
to
eco­
fresh
Carpet
Treatment
for
Fleas
b
Assumed
half
the
residues
are
available
since
rooms
treated
with
crack
and
crevice
products
have
hot
and
cool
zones
c
Boron
concentration
measurements
based
on
summary
data
presented
in
MeadWestvaco
Memorandum
dated
April
21,
2006.
d
Application
rate
÷
929
cm2/
square
foot
*
10%
dislodgeable
factor.
e
Application
rate
÷
929
cm2/
square
foot
*
1%
dislodgeable
factor
discussed
in
J.
D.
Lloyd,
1996.
f
MOE
=
NOAEL
(
8.8
mg/
kg/
day)/
daily
exposure
estimate
(
mg/
kg/
day)

6.3.1.4
Residential
Handler
Exposure­
Inerts
Inert
uses
were
also
identified
for
boric
acid
and
its
sodium
salts.
One
of
the
uses
is
in
pesticide
formulations
applied
to
agricultural
crops.
The
labels
for
these
products
specify
the
use
of
personal
protective
equipment
and
these
products
were
not
examined
as
part
of
this
assessment.
Another
inert
use
identified
was
application
of
tablets
or
pellets
to
swimming
pools.
Two
products
were
identified,
one
containing
1%
boric
acid
and
one
containing
0.5%
sodium
metaborate.
This
type
of
scenario
had
been
examined
with
products
containing
100%
of
sodium
tetraborate
pentahydrate
as
the
active
ingredient.
It
was
assumed
that
the
handler
MOEs
from
use
of
products
containing
either
boric
acid
or
sodium
metaborate
as
inert
ingredients
would
be
much
greater
than
the
use
of
a
product
containing
100%
of
sodium
tetraborate
pentahydrate.
However,
since
the
oral
MOEs
for
children
exposed
through
swimming
were
below
the
target
MOE
of
100
for
sodium
tetraborate
pentahydrate,
those
scenarios
were
re­
examined
using
the
information
available
for
boric
acid.
The
same
application
rate
was
assumed
and
a
correction
was
made
for
the
1%
weight
fraction
of
boric
acid
in
the
product.
The
MOEs
for
both
child
exposure
scenarios
(
7­
10
years
and
11­
14
years)
were
above
the
target
MOE
(
see
Table
6.3c).
The
third
inert
use
Page
55
of
84
identified
was
in
consumer
products,
such
as
general
purpose
cleaners,
which
contain
boric
acid
as
an
inert
ingredient
(
weight
fraction
=
15%).
It
was
expected
that
the
MOE
would
be
rather
small,
considering
the
results
from
the
examination
of
general
purpose
cleaners
containing
sodium
tetraborate
decahydrate
as
an
active
ingredient.
The
CEM
model
was
run
for
boric
acid
and
the
inhalation
MOE
was
calculated
to
be
16,000
(
see
Table
6.3a).
CEM
model
outputs
are
shown
in
Appendix
5.0.

6.3.1.5
Residential
Risk
Characterization­
Uncertainties
Associated
With
Residential
Postapplication
Exposures
Scenarios
for
residential
postapplication
exposure
to
sodium
tetraborate
pentahydrate
octaborate
from
ingestion
of
treated
swimming
pool
water
resulted
in
MOEs
for
children
age
7
to
10
years
that
were
less
than
the
target
MOE
of
100
(
ranging
from
65
to
690).
Several
factors
need
to
be
considered
when
interpreting
these
MOEs,
including:

(
1)
For
the
swimming
pool
exposure
scenarios
there
is
uncertainty
associated
with
the
assumption
that
the
pesticide
applied
will
not
dissipate.
The
draft
Children's
Exposure
Factors
Handbook
recommends
an
exposure
duration
of
60
minutes
per
event
(
based
on
one
event
per
month).
This
value
is
described
as
upper
while
a
30
minute
duration
is
described
as
central.
These
values
are
based
on
respondents
participating
in
the
National
Human
Activity
Pattern
Survey
and
answering
the
question
"
in
the
past
month,
did
you
swim
in
a
fresh
water
pool?"
The
difference
in
MOE
estimates
between
children
(
ages
7­
10)
and
children
(
ages
11­
14)
is
the
body
weight
assumptions
(
30
and
48
kg
respectively).
For
both
age
groups,
it
is
assumed
that
0.05
liters
of
water
are
ingested
per
hour.

(
2)
For
the
dust
formulations
applied
as
crack
and
crevice
treatments,
the
area
treated
is
based
on
an
assumption
of
the
size
of
an
average
room
and
that
the
area
treated
would
be
a
small
swath
of
carpet
along
the
edges
of
the
room.
Most
of
the
product
labels
recommend
that
the
products
be
applied
liberally
to
cracks
and
crevices
to
make
sure
that
no
powder
is
left
visible
on
indoor
surfaces.
In
the
assessment
it
was
assumed
that
the
powder
was
not
removed.
If
the
residues
were
removed
by
wiping
or
vacuuming,
the
MOE
would
likely
be
greater
than
100.

(
3)
Many
of
the
labels
state
that
children
should
not
be
present
during
application
of
pesticide
products.
This
would
reduce
the
likelihood
of
exposure
of
young
children
to
pesticide
residues
through
hand
to
mouth
behavior,
although
such
exposure
could
occur
postapplication.

(
4)
For
liquid
products
applied
directly
to
carpets,
use
of
a
hand
transfer
efficiency
of
5
percent
for
the
hand­
to­
mouth
pathway
is
likely
to
overestimate
exposure
for
the
oral
Page
56
of
84
route.
In
a
draft
letter
regarding
dislodgeable,
disodium
octaborate
tetrahydrate
(
DOT)
residues
measured
with
a
California
roller,
transfer
efficiencies
reported
ranged
from
0.04
to
0.09
percent.
A
discussion
of
the
study
is
presented
in
Krieger
et
al.,
1996;
Human
Disodium
Octaborate
Tetrahydrate
Exposure
Following
Carpet
Flea
Treatment
is
Not
Associated
with
Significant
Dermal
Absorption.
Several
residue
collection
devices
are
available
to
investigators.
In
a
round
robin
comparison
of
indoor
residue
collection
methods,
it
was
suggested
that
the
California
roller
had
similar
transfer
efficiency
as
the
polyurethane
foam
roller
(
UF).
In
subsequent
testing,
the
transfer
efficiency
of
the
UF
roller
was
also
compared
to
the
efficiency
of
wet
hands.
ORD
determined
that
the
transfer
efficiency
of
wet
hands
was
1.5
to
3
times
higher
than
the
UF
roller.
The
highest
percent
(
5)
is
used
in
the
screening
level
assessment
performed
in
this
assessment.
It
is
likely
that
the
5
percent
transfer
efficiency
assumption
used
in
the
hand­
to­
mouth
assessment
for
DOT
overestimates
the
exposure
and
risk.
However,
since
the
DOT
findings
are
reported
in
a
draft
letter,
and
the
round
robin
testing
did
not
include
any
measurements
of
DOT,
it
is
recommended
that
confirmatory
hand
press
data
be
collected
by
the
registrants
to
refine
the
hand­
to­
mouth
exposure
estimates
for
carpets
treated
with
forms
of
boric
acid.

6.3.2
Other
(
Spray
Drift,
etc.)

Spray
drift
is
always
a
potential
source
of
exposure
to
residents
nearby
to
spraying
operations.
This
is
particularly
the
case
with
aerial
application
(
there
are
currently
no
aerial
applications
for
boric
acid
or
sodium
borate
salts),
but,
to
a
lesser
extent,
could
also
be
a
potential
source
of
exposure
from
the
ground
application
method
employed
for
boric
acid
and
sodium
borate
salts.
The
Agency
has
been
working
with
the
Spray
Drift
Task
Force,
EPA
Regional
Offices
and
State
Lead
Agencies
for
pesticide
regulation
and
other
parties
to
develop
the
best
spray
drift
management
practices.
On
a
chemical
by
chemical
basis,
the
Agency
is
now
requiring
interim
mitigation
measures
for
aerial
applications
that
must
be
placed
on
product
labels/
labeling.
The
Agency
has
completed
its
evaluation
of
the
new
data
base
submitted
by
the
Spray
Drift
Task
Force,
a
membership
of
U.
S.
pesticide
registrants,
and
is
developing
a
policy
on
how
to
appropriately
apply
the
data
and
the
AgDRIFT
computer
model
to
its
risk
assessments
for
pesticides
applied
by
air,
orchard
airblast
and
ground
hydraulic
methods.
After
the
policy
is
in
place,
the
Agency
may
impose
further
refinements
in
spray
drift
management
practices
to
reduce
off­
target
drift
with
specific
products
with
significant
risks
associated
with
drift.
Page
57
of
84
7.0
Aggregate
Risk
Assessments
and
Risk
Characterization
Aggregate
exposure
assessments
were
not
performed
for
boric
acid
and
sodium
borate
salts.
This
decision
was
based
on
several
considerations
as
discussed
below.

An
assessment
of
dietary
exposure
was
not
conducted.
Boron
is
a
naturally
occurring
component
of
food
and
water
and
may
be
a
necessary
nutrient
at
trace
levels,
although
no
minimum
daily
requirement
has
been
established.
Boric
acid
and
sodium
borate
salts
are
exempt
from
tolerances
and
therefore
residue
data
were
not
submitted
for
the
food/
feed
uses.
The
exemption
was
granted
based
on
the
natural
occurrence
of
boron
in
the
diet
and
on
limited
residue
data
(
citrus
and
cottonseed,
submitted
to
support
earlier
tolerances
that
were
later
revoked)
indicating
that
pesticide
residues
from
these
applications
would
not
contribute
significantly
to
total
dietary
boron.
In
fact,
the
levels
of
boron
in
commodities
treated
post­
harvest
(
not
a
currently
registered
use)
with
boric
acid
were
virtually
indistinguishable
to
the
levels
of
boron
occurring
naturally
in
untreated
commodities.
Boric
acid
and
its
sodium
salts
are
also
used
as
inert
ingredients
(
at
much
smaller
concentrations
than
when
used
as
an
active
ingredient)
in
both
food
and
non­
food
use
pesticide
products.
A
tolerance
exemption
for
use
in
products
applied
to
growing
crops
is
currently
established.

It
is
noted
that
there
may
be
considerable
variability
in
boron
consumption
from
natural
dietary
sources,
depending
on
the
type
of
diet
consumed
and
natural
variations
in
drinking
water
levels.
In
general,
vegetarian
diets
would
provide
a
higher
daily
intake
than
omnivorous
diets.
Some
dietary
supplements
may
also
contain
trace
levels
of
boron.
Estimates
of
daily
boron
intake
vary,
ranging
in
the
United
States
from
0.26
to
7.1
mg/
day
with
a
mean
of
1.9
mg/
day
(
0.03
mg/
kg/
day)(
Moore,
1997).
Other
survey
data
provide
average
daily
dietary
boron
intake
values
of
0.5
to
3.1
mg/
day
(
0.007
to
0.044
mg/
kg/
day)(
Nielsen,
1991).
The
FDA
determined
an
average
U.
S.
adult
male
dietary
boron
intake
of
1.52
mg/
day
(
0.025
mg/
kg/
day)(
Iyengar
et
al.,
1988).
Rainey
et
al.
(
1999)
also
provided
analyses
of
boron
intake
in
the
United
States
by
age
and
gender,
as
well
as
for
vegetarian/
non­
vegetarian
diets.
Dietary
exposure
to
boron
is
therefore
unlikely
to
exceed
the
level
of
concern
in
most
circumstances
and
the
contribution
from
residues
of
boric
acid/
sodium
borate
salt
pesticides
to
these
levels
should
not
result
in
a
significant
increase.

It
should
also
be
noted
that
the
dose
selected
as
the
NOAEL
(
8.8
mg/
kg/
day
in
dogs)
for
use
in
the
risk
assessment
was
based
on
boric
acid/
sodium
borate
added
to
the
animals'
diets
and
did
not
include
background
boron
intake
from
naturally
occurring
levels
in
the
basal
diet
and
drinking
water:
the
actual
dietary
intake
of
boron
(
and
therefore
the
total
boron
dose)
would
be
expected
to
be
higher
than
8.8
mg/
kg/
day
when
the
naturally
occurring
boron
levels
in
the
basal
diet
and
drinking
water
for
these
animals
were
added.
However,
background
dietary
boron
exposure
information
for
the
animal
studies
was
unavailable
and
were
therefore
not
estimated
for
Page
58
of
84
this
assessment.

Postapplication
exposures
to
children
age
7
to
10
years
from
swallowing
treated
swimming
pool
water
at
concentrations
$
480
mg/
L
of
sodium
tetraborate
pentahydrate
showed
MOEs
that
were
below
100;
a
lower
concentration
of
240
mg/
L
showed
acceptable
MOEs
(
150).
Therefore,
the
exposures
to
children
from
these
uses
filled
the
risk
cup.
Therefore,
even
though
the
MOEs
for
residential
handlers/
applicators
were
not
of
concern
(>
800);
an
aggregate
exposure
is
not
conducted
when
risks
(
in
this
case
from
postapplication
exposures
to
children)
exceed
the
level
of
concern.
Use
of
the
product
at
the
lowest
concentration
would
not
fill
the
risk
cup.

The
Agency
also
considered
exposures
from
non­
pesticidal
sources
of
boron
(
found
in
laundry
detergent
and
general
purpose
cleaners)
as
well
as
from
inerts
in
pesticidal
products.
Inhalation
exposures
to
consumer
products
containing
boric
acid
or
borax
were
below
the
level
of
concern
(
MOEs
$
16,000).
Residential
postapplication
incidental
oral
exposure
to
swimming
pool
treatment
products
containing
boric
acid
as
an
inert
rather
than
an
active
ingredient
also
did
not
exceed
the
level
of
concern
for
either
children
or
adults
(
MOEs$
5,600).
Based
on
the
large
MOEs
for
these
exposure
scenarios,
they
would
not
be
a
significant
source
of
boron
internal
dosing
and
would
not
contribute
significantly
to
total
daily
boron
exposure
compared
to
the
diet.

8.0
Cumulative
Risk
Characterization/
Assessment
Unlike
other
pesticides
for
which
EPA
has
followed
a
cumulative
risk
approach
based
on
a
common
mechanism
of
toxicity,
EPA
has
not
made
a
common
mechanism
of
toxicity
finding
as
to
boric
acid
and
its
sodium
salts
and
any
other
substances
and
boric
acid/
sodium
salts
do
not
appear
to
produce
a
toxic
metabolite
produced
by
other
substances.
For
the
purposes
of
this
tolerance
action,
therefore,
EPA
has
not
assumed
that
boric
acid/
sodium
salts
have
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/
Risk
Pathway
Characterization
of
nonresidential
occupational
exposure
and
risk
are
not
required
at
this
time
because
this
assessment
is
for
a
tolerance
reassessment
only.
Page
59
of
84
10.0
Data
Needs
and
Label
Requirements
10.1
Toxicology
No
additional
toxicology
data
are
required
at
this
time.

10.2
Residue
Chemistry
No
residue
chemistry
data
are
required
at
this
time.
Boric
acid
and
its
salts
are
currently
exempt
from
tolerances.
Tolerances
on
citrus
(
8
ppm)
and
cottonseed
(
30
ppm)
were
revoked
upon
granting
of
the
exemption.
Except
for
citrus
and
cottonseed,
studies
on
the
magnitude
of
boron
residues
have
not
been
submitted
for
boric
acid
and
sodium
borate
salts
because
of
the
tolerance
exemption.
In
the
future,
new
agricultural
uses
may
trigger
residue
data
requirements
to
confirm
low
contribution
of
these
active
ingredients
to
total
naturally­
occurring
boron
levels.

10.3
Occupational
and
Residential
Exposure
Additional
data
to
confirm
the
values
used
to
assess
postapplication
exposures
for
wood
treatment
and
crack
and
crevice/
carpet
treatment
exposure
scenarios
are
required.

References:

MRID
NUMBERS
(
DATA
SUBMISSIONS)

00005592
United
States
Borax
&
Chemical
Corporation
Toxicity
Data
for
Boric
Acid
Esters,
Elemental
Boron,
and
Other
Borates.
(
Unpublished
study
received
Apr
9,
1958
under
unknown
admin.
no.;
CDL:
110723­
A)
.

00005622
Weir,
R.
J.
(
1966)
Final
Report:
Two­
Year
Dietary
Feeding­
Dogs.
Hazleton
Laboratories,
Falls
Church,
VA,
Project
No.
182­
106,
July
8,
1966;
submitted
by
United
States
Borax.
Unpublished
report.

00005624
Weir,
R.
J.
(
1967)
Final
Report:
38­
Week
Dietary
Feeding­
Dogs.
Hazleton
Laboratories,
Falls
Church,
VA,
February,
1967;
submitted
by
United
States
Borax.
Unpublished
report.

00006719
Hazleton
Laboratories,
Incorporated
(
1962)
Toxicity
of
Borax
and
Boric
Acid.
Received
Jun
25,
1969
under
1624­
96;
submitted
by
United
States
Borax
&
Page
60
of
84
Chemical
Corp.,
Los
Angeles,
Calif.
Unpublished
report.

00064203
Paynter,
O.
E.,
Kundzin,
M
and
Kundzin,
T.
(
1963)
Boric
Acid
90­
Day
Dietary
Feeding­
Dogs.
Hazleton
Laboratories,
Falls
Church,
VA,
January
17,
1963;
submitted
by
United
States
Borax
and
Chemical
Corp.,
Unpublished
report.

00064208
Keller,
J.
G.
(
1962)
Acute
Oral
Administration­­
Dogs:
Boric
Acid.
Received
March
5,
1981
under
1624­
117;
prepared
by
Hazleton
Laboratories,
Inc.,
submitted
by
United
States
Borax
&
Chemical
Corp.,
Los
Angeles,
CA.
Unpublished
report.

00064209
Estep,
C.
L.
and
Teske,
R.
H.
(
1968)
Acute
Application
of
Sample
713
123A
to
the
Eyes
of
Rabbits:
S­
152A.
Received
Mar
5,
1981
under
1624­
117;
prepared
by
Hill
Top
Research,
Inc.,
submitted
by
United
States
Borax
&
Chemical
Corp.,
Los
Angeles,
Calif.
Unpublished
report.

00068025
Paynter,
O.
E.,
Kundzin,
M.
and
Kundzin,
T.
(
1962)
Boric
Acid
90­
Day
Dietary
Feeding­
Rats.
Hazleton
Laboratories,
Falls
Church,
VA,
December
12,
1962;
submitted
by
United
States
Borax.
Unpublished
report.

00068882
Weir,
R.
J.
and
Crews,
L.
M.
(
1966)
Final
Report:
Three­
Generation
Reproduction
Study­
Rats.
Hazleton
Laboratories,
Falls
Church,
VA,
Project
No.
182­
105,
July
8,
1966;
submitted
by
United
States
Borax.
Unpublished
report.

00068883
Weir,
R.
J.
and
Wright,
D.
(
1966)
Final
Report:
Two­
Year
Dietary
Administration­
Albino
Rats.
Hazleton
Laboratories,
Falls
Church,
VA,
Project
No.
182­
104,
July
8,
1966;
submitted
by
United
States
Borax.
Unpublished
report.

00106011
Conine,
D.,
Weiner,
A.,
Kreuzmann,
J.
et
al.
(
1982)
Acute
Dermal
Toxicity
Screen
in
Rabbits:
Primary
Skin
Irritation
Study
in
Rabbits
of
Boric
Acid
(
OA
107­
3)
for
U.
S.
Borax
Research
Corporation:
Hill
Top
Research
Project
No.
82­
0280­
21.
Received
Jul
12,
1982
under
1624­
116;
prepared
by
Hill
Top
Research,
Inc.,
submitted
by
United
States
Borax
&
Chemical
Corp.,
Los
Angeles,
CA.
Unpublished
report.

40692301
Meyding,
G.
D.
(
1961)
Acute
Oral
Administration
­
Rats
with
Sodium
Tetraborate
Decahydrate.
Hazleton­
Nuclear
Science
Corp.,
Palo
Alto,
CA.
No
study
number
provided.
January
25,
1961.
Unpublished
report.

40692302
Meyding,
G.
D.
(
1961)
Acute
Oral
Administration
­
Rats
with
Sodium
Tetraborate
Decahydrate.
Hazleton
Laboratories,
Inc.,
Vienna,
VA.
No
study
number
Page
61
of
84
provided.
August
2,
1961.
Unpublished
report.

40692303
Keller,
J.
G.
(
1962)
Acute
Oral
Administration
­
Rats
with
Borax
(
Sodium
Tetraborate
Decahydrate).
Hazleton
Laboratories,
Inc.,
Vienna,
VA.
No
study
number
provided.
March
16,
1962.
Unpublished
report.

40692304
Keller,
J.
G.
(
1962)
Acute
Oral
Administration
­
Dogs
with
Borax
(
Sodium
Tetraborate
Decahydrate).
Hazleton
Laboratories,
Inc.,
Vienna,
VA.
No
study
number
provided.
March
16,
1962.
Unpublished
report.

40692305
Paynter,
O.
E.
(
1962)
90­
Day
Dietary
Administration
­
Rats
with
20
Mule
Team
Borax
(
Sodium
Tetraborate
Decahydrate).
Hazleton
Laboratories,
Inc.,
Falls
Church,
VA.
No
study
no.
provided,
December
13,
1962.
Unpublished
report.

40692306
Weir,
R.
J.
(
1963)
90­
Day
Dietary
Administration
­
Rats
with
20
Mule
Team
Borax
(
Sodium
Tetraborate
Decahydrate).
Hazleton
Laboratories
Inc.,
Vienna,
VA.
No
study
number
provided.
February
15,
1963.

40692307
Paynter,
O.
E.
(
1963)
90­
Day
Dietary
Feeding
­
Dogs
with
20
Mule
Team
Borax
(
Sodium
Tetraborate
Decahydrate).
Hazleton
Laboratories,
Inc.,
Falls
Church,
VA.
No
study
number
provided,
January
17,
1963.
Unpublished
report.

40692308
Weir,
R.
J.
(
1967)
38­
Week
Dietary
Feeding
­
Dogs
with
20
Mule
Team
Borax
(
Sodium
Tetraborate
Decahydrate).
Hazleton
Laboratories,
Inc.,
Falls
Church,
VA.
No
study
number
provided.
February
28,
1967.
Unpublished
report.

40692309
Weir,
R.
J.
and
Crews,
L.
M.
(
1967)
Two
Year
Dietary
Administration
­
Albino
Rats.
Borax
(
Sodium
Tetraborate
Decahydrate)
and
Addendum.
Hazleton
Laboratories,
Inc.,
Falls
Church,
VA.
Laboratory
Project
ID
182­
104,
April
10,
1967
(
original
report
on
July
8,
1966).
Unpublished
report.

40692310
Weir,
R.
J.
and
Crews,
L.
M.
(
1967)
Two
Year
Dietary
Feeding
­
Dogs.
Borax
(
Sodium
Tetraborate
Decahydrate)
and
Addendum.
Hazleton
Laboratories,
Inc.,
Falls
Church,
VA.
Laboratory
Project
ID
182­
106,
April
10,
1967
(
original
study
on
July
8,
1966).
Unpublished
report.

40692311
Weir,
R.
J.
and
Crews,
L.
M.
(
1966)
Three­
Generation
Reproductive
Study
­
Rats
with
Borax
(
Sodium
Tetraborate
Decahydrate)
and
Addendum.
Hazleton
Laboratories,
Inc.,
Vienna,
VA.
Study
No.:
Project
182­
105,
July
8,
1966.
Unpublished
report.
Page
62
of
84
41589101
Fail,
George,
Grizzle
et
al.
(
1990)
Reproductive
Toxicity
of
Boric
Acid
in
CD­
1
Swiss
Mice.
NTP,
NIEHS,
Research
Triangle
Park,
N.
C.
Study
Number
90­
105,
April
13,
1990.
Unpublished
report.

41725401
Field,
E.
A.,
Price,
C.
J.,
Marr,
M.
C.
et
al.
(
1990)
Final
Report
on
the
Developmental
Toxicity
of
Boric
Acid
(
CAS
No.
10043­
35­
3)
in
Sprague­
Dawley
Rats.
EPA
Reg.
No.
1624­
117.
Research
Triangle
Institute
and
National
Toxicology
Program.
Study
Number
Rt88­
BORT,
May
1,
1990.
Published
report.

41725402
Field,
E.
A.,
Price,
C.
J.,
Marr,
M.
C.
et
al.
(
1990)
Final
Report
on
the
Developmental
Toxicity
of
Boric
Acid
(
CAS
No.
10043­
35­
3)
in
CD­
1
Swiss
Mice.
EPA
Reg.
No.
1624­
117.
Research
Triangle
Institute
and
National
Toxicology
Program.
Study
Number
M188­
BORT,
December
14,
1990.
Published
report.

41861301
Dieter,
M.,
Bishop,
J.,
Eustis,
S.
Haseman,
J.
et
al.
(
1991)
Toxicology
and
Carcinogenesis
of
Boric
Acid
in
B6C3F1
Mice,
NTP
Technical
Report
Series
324.
E.
G.
and
G.
Mason
Research
Institute,
Study
No.
TR324,
April,
1991.
Published
report.

42038901
Steward,
K.
R.
(
1991)
Salmonella/
Microsome
Plate
Incorporation
Assay
of
Boric
Acid.
SRI
International,
Inc.,
Menlo
Park,
CA.
Study
No.
2389­
A200­
91,
August
12,
1991.
Unpublished
report.

42038902
Rudd,
C.
J.
(
1991)
Mouse
Lymphoma
Cell
Mutagenesis
Assay
(
tk+/­/
tk­/­)
of
Boric
Acid.
SRI
International,
Menlo
Park,
CA.
Study
Number
2389­
G300­
91,
August
23,
1991.
Unpublished
report.

42038903
Bakke,
J.
P.
(
1991)
Evaluation
of
the
Potential
of
Boric
Acid
to
Induce
Unscheduled
DNA
Synthesis
in
In
Vitro
Hepatocyte
DNA
Repair
Assay
Using
the
Male
F­
344
Rat.
SRI
International,
Menlo
Park,
CA.
Study
Number
2389­
V500­
91,
August
21,
1991.
Unpublished
report.

42038904
O'Loughlin,
K.
G.
(
1991)
Bone
Marrow
Erythrocyte
Micronucleus
Assay
of
Boric
Acid
in
Swiss­
Webster
Mice.
SRI
International,
Menlo
Park,
CA.
Study
Number
2389­
C400­
91,
August
19,
1991.
Unpublished
report.
Page
63
of
84
42164201
Price,
C.,
Marr,
M.
and
Myers,
C.
et
al.
(
1991)
Developmental
Toxicity
of
Boric
Acid
in
New
Zealand
White
Rabbits.
NTP
and
Chemistry
and
Life
Sciences,
Research
Triangle
Park,
NC.
Study
No.
Rb90­
BPORA,
October
30,
1991.
Published
report.

42164202
Price,
C.;
Marr,
M.
and
Myers,
C.;
et
al.
(
1991)
Laboratory
Supplement
for
Final
Report
on
the
Development
Toxicity
of
Boric
Acid
in
New
Zealand
White
Rabbits.
National
Institute
of
Environmental
Health
Science
and
Research
Triangle
Institute,
Lab
Project
Number:
RB90­
BORA.
Unpublished
report.

43340101
Price,
C.
J.,
Marr,
M.
C.
and
Myers,
C.
B.
(
1994)
Determination
of
NOAEL
for
Developmental
Toxicity
in
Sprague
Dawley
Rats
Exposed
to
Boric
Acid
in
Feed
on
Gestation
Days
0­
20
and
Evaluation
of
Post
Natal
Recovery
Through
Post
Natal
Day
21.
Reproduction
and
Developmental
Toxicology
Labs,
RTI,
RTP,
North
Carolina.
Study
Number
65C5657­
200,
August
8,
1994.
Unpublished
report.

43500701
Wnorowski,
G.
(
1994)
Acute
Inhalation
Toxicity
Limit
Test
on
Boric
Acid
(
in
Rats).
Product
Safety
Labs,
East
Brunswick,
NJ.
Study
No.
3311,
November
28,
1994.
Unpublished
report.

43553201
Reagan,
E.
and
Becci,
P.
(
1985)
Acute
Dermal
Toxicity
Study
of
20
Mule
Team,
Lot
USB­
11­
84
Sodium
Tetraborate
Decahydrate
in
New
Zealand
White
Rabbits.
Food
and
Drug
Research
Laboratories,
Inc.,
Waverly,
NY.
Study
Report
No.
FDRL
8403A,
February
20,
1985.
Unpublished
report.

43553202
Reagan,
E.
and
Becci,
P.
(
1985)
Primary
Eye
Irritation
Study
of
20
Mule
Team,
Lot
USB­
11­
84
Sodium
Tetraborate
Decahydrate
in
New
Zealand
White
Rabbits.
Food
and
Drug
Research
Laboratories,
Inc.,
Waverly,
NY.
Study
Report
No.
FDRL
8403A,
February
8,
1985.
Unpublished
report.

43553203
Reagan,
E.
and
Becci,
P.
(
1985)
Primary
Dermal
Irritation
Study
of
20
Mule
Team,
Lot
USB­
11­
84
Sodium
Tetraborate
Decahydrate
in
New
Zealand
White
Rabbits.
Food
and
Drug
Research
Laboratories,
Inc.,
Waverly,
NY.
Study
Report
No.
FDRL
8403A,
January
23,
1985.
Unpublished
report.

44383601
Wnorowski,
G.
(
1994)
Acute
Inhalation
Toxicity
Limit
Test
on
Boric
Acid
(
in
Rats).
Product
Safety
Labs,
East
Brunswick,
NJ.
Study
No.
5257,
July
11,
1997.
Unpublished
report.
Page
64
of
84
44459801
Merricks,
L.
D.
(
1997)
Carbaryl,
Mixer/
Loader/
Applicator
Exposure
Study
During
Application
of
RP­
2
Liquid(
21%),
Sevin
Ready
to
Use
Insect
Spray
or
Sevin
10
Dust
to
Home
and
Garden
Vegetables.
Unpublished
report.

45250702
Pontal,
P.
(
1996)
Fipronil,
Worker
Exposure
Study
During
the
Application
of
Reagent
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Banana
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Unpublished
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45333401
Merricks,
L.
D.
(
2001)
Determination
of
Dermal
(
hands
and
forearms)
and
Inhalation
Exposure
to
Disulfoton
Resulting
from
Residential
Applications
of
Bayer
Advanced
Garden
2
in
1
Systemic
Rose
and
Flower
Care
to
Shrubs.
Unpublished
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46852201
Draize,
J.
H.
and
Kelley,
E.
A.
(
1959)
The
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Acid
Preparations
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Administration
and
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Applications
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Toxicol
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267­
276.

46852202
Krieger,
R.
L.;
Dinoff,
T.
M.;
and
Peterson,
J.:
(
1996)
Human
Disodium
Octaborate
Tetrahydrate
Exposure
Following
Carpet
Flea
Treatment
is
Not
Associated
with
Significant
Dermal
Exposure.
Journal
of
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Analysis
and
Environmental
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6,
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279­
288.

MRID
to
be
Bakke,
J.
P.
(
1992)
Evaluation
of
the
Potential
of
Boric
Acid
to
Induce
assigned
Unscheduled
DNA
Sunthesis
in
In
Vitro
Hepatocyte
DNA
Repair
Assay
Using
the
Male
F­
344
Rat:
Final
Report
Amendment
One.
SRI
International,
Menlo
Park,
CA.
Study
Project
LSC­
2389­
500;
Study
Number
2389­
V500­
91,
August
23,
1992.
Unpublished
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Lake,
M.
A.
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McIntyre,
M.
A.
(
2006)
Formosan
Termite
Response
to
Weathered
Borate­
Treated
Wood:
Paper
given
to
at
the
Forest
Products
Society
meeting
held
in
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Orleans,
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March
26.

Lloyd,
J.
D.
(
1996)
Indicative
Study
of
the
Post
In
Situ
Treatment
Pick­
Up
of
Disodium
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Tetrahydrate.

HED/
EPA
DOCUMENTS
The
PHED
Task
Force
(
1995)
The
Pesticide
Handlers
Exposure
Database,
Version
1.1.
Task
Force
Members
Health
Canada,
U.
S.
Environmental
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and
the
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Agricultural
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released
February,
1995.
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65
of
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1993)
Reregistration
Eligibility
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and
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Office
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and
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(
7508W).
EPA
738­
R­
93­
017.

U.
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2005)
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Risk
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Risk
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2005.
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630/
p­
03/
001F.

U.
S.
EPA
IRIS
(
2004)
Toxicological
Review
of
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and
Compounds.
June,
2004,
EPA
635/
04/
052
(
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epa.
gov/
iris).

U.
S.
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Science
Advisory
Council
(
SAC)
for
Exposure
(
2001)
Policy
12:
Revised
Residential
SOP
Assumptions
(
February
22,
2001).

Versar,
Inc.
(
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Consumer
Exposure
Module
(
CEM),
Version
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Prepared
for
the
Economics,
Exposure
and
Technology
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of
the
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and
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Substances.

Versar,
Inc.
(
2001)
SWIMODEL,
Version
2.0.
Prepared
for
the
Office
of
Pesticide
Programs,
Antimicrobial
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AND
OTHER
DOCUMENTS
Agency
for
Toxic
Substances
and
Disease
Registry
(
ATSDR)
(
1992)
Toxicological
Profile
for
Boron
and
Compounds.
U.
S.
Public
Health
Service.

Anderson,
D.
L.,
Cunningham,
W.
C.
and
Lindstrom,
T.
R.
(
1994)
Concentrations
and
Intakes
of
H,
B,
S,
K,
Na,
Cl
and
NaCl
in
Foods.
Journal
of
Food
Comp.
and
Anal.
7:
59­
82.

California
Department
of
Pesticide
Regulation
(
CDPR)(
1996).
Memorandum
from
T.
Formoli,
Worker
Health
and
Safety
Branch,
to
Karen
Fletcher.
HSM­
96004.
Dated
March
27,
1996.

Chapin,
R.
E.
and
Ku,
W.
W.
(
1994)
The
Reproductive
Toxicity
of
Boric
Acid.
Environ.
Health
Perspect.
102(
Suppl.
7):
87­
91.

ECETOX
European
Centre
for
Ecotoxicology
and
Toxicology
of
Chemicals.
(
1995)
Technical
Report
No.
63.

Fail,
P.
A.,
Chapin,
R.
E.,
Price,
C.
J.
et
al.
(
1998)
General,
Reproductive,
Developmental
and
Endocrine
Toxicity
of
Boronated
Compounds.
Reprod.
Toxicol
12:
1­
18.
Page
66
of
84
Iyengar,
G.
V.,
Clarke,
W.
B.,
Downing,
R.
G.
et
al.
(
1988)
Lithium
in
biological
and
dietary
materials.
Trace
Elem.
Anal.
Chem.
Med.
Biol.
5:
267­
269.

Ku,
W.
W.
and
Chapin.
R.
E.
(
1994)
Mechanism
of
the
Testicular
Toxicity
of
Boric
Acid
in
Rats.
In
Vivo
and
In
Vitro
Studies.
Environ.
Health
Perspect.
102(
Suppl.
7):
99­
105.

Material
Safety
Data
Sheet
for
20
Mule
Team
®
Tim­
bor
®
Industrial
(
1996)
Ecological
information
providing
percent
of
boron
in
disodium
octaborate
tetrahydrate.
http://
www.
bpbcorp.
com/
boratesht.
html
Moore,
J.
A.
(
1997)
An
Assessment
of
Boric
Acid
and
Borax
Using
the
IEHR
Evaluative
Process
for
Assessing
Human
Developmental
and
Reproductive
Toxicity
of
Agents.
Expert
Scientific
Committee.
Reprod.
Toxicol.
11(
1):
123­
160.

Murray,
F.
J.
(
1995)
A
Human
Health
Risk
Assessment
of
Boron
(
Boric
Acid
and
Borax)
in
Drinking
Water.
Res.
Tox.
Pharm.
22:
221­
230.

Naghii,
M.
R.
and
Samman,
S.
(
1996)
The
boron
content
of
Selected
Foods
and
the
Estimation
of
its
Daily
Intake
Among
Free­
Living
Subjects.
J.
Am.
College
Nutr.
15(
6):
614­
619.

Narotsky,
M.
G.,
Wery,
N.
and
Hamby,
B.
T.
et
al.
(
2003)
Effects
of
Boric
Acid
on
Hox
Gene
Expression
and
the
Axial
Skeleton
in
the
Developing
Rat.
In:
Massaro,
E.
J
and
Rogers,
J.
M.,
eds.
The
Skeleton:
Biochemical,
Genetic
and
Molecular
Interactions
in
Development
and
Homeostasis.
Totowa,
NJ,
Humana
Press.

National
Academy
of
Sciences
Dietary
(
2001)
Reference
Intakes­
Vitamin
A,
Vitamin
K,
Arsenic,
Boron,
Chromium,
Copper,
Iodine,
Iron,
Manganese,
Molybdenum,
Nickel,
Silicon,
Vanadium
and
Zinc.
2001.
Food
and
Nutrition
Board,
Institute
of
Medicine,
p.
773.

National
Institute
for
Occupational
Safety
and
Health
(
NIOSH).
(
2001)
International
Chemical
Safety
Cards
(
ICSC):
Boric
Acid
­­
0991;
Sodium
tetraborate
decahydrate
­­
0567;
Sodium
tetraborate
­­
1229.
http://
www.
cdc.
gov/
niosh/
npg/
npg.
html
Nielsen,
F.
H.
(
1991)
Nutritional
Requirements
for
Boron,
Silicon,
Vanadium,
Nickel
and
Arsenic:
Current
Knowledge
and
Speculation.
FASEB
J.
5:
2661­
2667.

Rainey,
C.
J.,
Nyquist,
L.
A.,
and
Strong,
R.
E.
et
al.
(
1999)
Daily
Boron
Intake
from
the
American
Diet.
J.
Am.
Diet
Assoc.
99(
3):
335­
340.

Wery,
N.,
Narotsky,
M.
G.,
Pacico,
N.
et
al.
(
2003)
Defects
in
Cervical
Vertebrae
in
Boric­
Acid
Page
67
of
84
Exposed
Rat
Embryos
are
associated
with
Anterior
Shifts
of
Hox
Gene
Expression
Domains.
Birth
Defects
Res.
(
Part
A)
67:
59­
67.

World
Health
Organization
(
WHO).
(
1998)
Environmental
Health
Criteria
204:
Boron.
International
Programme
on
Chemical
Safety
(
IPCS).
Geneva,
Switzerland.
ISBN
92
4
157204
3.
http://
www.
inchem.
org/
documents/
ehc/
ehc/
ehc204.
htm
Page
68
of
84
Appendices
1.0
TOXICOLOGY
DATA
REQUIREMENTS
The
requirements
(
40
CFR
158.340)
for
food
and
non­
food
uses
of
boric
acid
and
its
sodium
salts
are
presented
below
in
Table
1.
Use
of
the
new
guideline
numbers
does
not
imply
that
the
new
(
1998)
guideline
protocols
were
used.

Test
Technical
Required
Satisfied
870.1100
Acute
Oral
Toxicity
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
870.1200
Acute
Dermal
Toxicity
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
870.1300
Acute
Inhalation
Toxicity
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
870.2400
Primary
Eye
Irritation
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
870.2500
Primary
Dermal
Irritation
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
870.2600
Dermal
Sensitization
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
yes
yes
yes
yes
yes
no
yes
yes
yes
yes
yes
­

870.3100
Oral
Subchronic
(
rodent)
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
870.3150
Oral
Subchronic
(
nonrodent)
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
870.3200
21­
Day
Dermal
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
870.3250
90­
Day
Dermal
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
870.3465
28­
Day
Inhalation
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
yes
yes
no
no
no
yes
yes
­
­
­

870.3700a
Developmental
Toxicity
(
rodent)
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
870.3700b
Developmental
Toxicity
(
nonrodent)
.
.
.
.
.
.
.
.
.
.
.
.
870.3800
Reproduction
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
yes
yes
yes
yes
yes
yes
870.4100a
Chronic
Toxicity
(
rodent)
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
870.4100b
Chronic
Toxicity
(
nonrodent)
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
870.4200a
Oncogenicity
(
rat)
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
870.4200b
Oncogenicity
(
mouse)
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
870.4300
Chronic/
Oncogenicity
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
yes
yes
yes
yes
yes
yes
yes
yes
yes
yes
870.5100
Mutagenicity 
Gene
Mutation
­
bacterial
.
.
.
.
.
.
.
.
870.5300
Mutagenicity 
Gene
Mutation
­
mammalian
.
.
.
.
.
.
870.5xxx
Mutagenicity 
Structural
Chromosomal
Aberrations
870.5xxx
Mutagenicity 
Other
Genotoxic
Effects
.
.
.
.
.
.
.
.
.
.
yes
yes
yes
yes
yes
yes
yes
yes
870.6100a
Acute
Delayed
Neurotox.
(
hen)
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
870.6100b
90­
Day
Neurotoxicity
(
hen)
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
870.6200a
Acute
Neurotox.
Screening
Battery
(
rat)
.
.
.
.
.
.
.
.
.
870.6200b
90
Day
Neuro.
Screening
Battery
(
rat)
.
.
.
.
.
.
.
.
.
.
.
870.6300
Develop.
Neuro
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
no
no
no
no
no
­
­
­
­
­

870.7485
General
Metabolism
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
870.7600
Dermal
Penetration
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
no
no
­
­

Special
Studies
for
Ocular
Effects
Acute
Oral
(
rat)
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
Subchronic
Oral
(
rat)
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
Six­
month
Oral
(
dog)
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
no
no
no
­
­
­
Page
69
of
84
2.0
NON­
CRITICAL
TOXICOLOGY
STUDIES
(
1)
In
a
subchronic
oral
toxicity
study
(
MRID
40692305),
sodium
tetraborate
decahydrate
(
borax
technical,
about
105%
of
theoretical)
was
administered
to
10
Charles
River
Sprague
Dawley
rats/
sex/
dose
in
the
diet
at
dose
levels
of
0,
0.0463%,
0.154%,
0.463%,
1.54%
or
4.63%
(
equivalent
to
an
average
daily
intake
of
0,
34,
113,
339,
1057
or
4610
mg/
kg/
day
test
material;
0,
4.0,
14,
42,
125
or
544
mg/
kg/
day
boron
equivalents)
for
13
weeks.

At
0.0463%,
testicular
atrophy
in
4/
10
males
was
reported,
with
these
animals
also
showing
reduced
testicular
weights.
However,
since
a
dose­
response
was
not
observed
at
0.154%
(
0/
10)
and
0.463%
(
1/
10),
this
was
not
considered
a
treatment­
related
finding
(
further
supported
by
lack
of
testicular
effects
at
these
dose
levels
in
another
rat
subchronic
study,
MRID
40692306,
and
a
chronic
rat
study,
MRID
40692309).
The
incidence
of
testicular
atrophy
at
the
low
dose,
together
with
a
reduction
in
body
weight
gain
in
the
early
weeks
of
the
study,
but
not
after
week
4
of
the
study,
suggest
a
possible
error
in
dosage
or
animal
group
mixup
at
the
study
start.
At
1.54%,
clinical
signs
of
toxicity
(
beginning
during
the
first
week
of
treatment
and
including
rapid
respiration,
hunched
posture,
thinness,
swollen
paws,
inflamed
eyes,
coarse
fur/
desquamation;
during
the
later
weeks,
protruding
penis
and
shrunken
scrotum
in
males
and
an
unsteady
gait
in
3
females
were
observed;
incidence
for
most
signs
not
given
in
report),
decreased
body
weight/
weight
gain
(
beginning
in
the
first
weeks
of
the
study)
in
males
(­
53%/­
67%
at
termination
below
controls)
and
females
(­
19%/­
32%
below
controls
at
termination),
decreased
weekly
food
consumption
(
on
a
g/
animal/
day
basis
reduced
about
40­
50%
below
controls)
and
testicular
atrophy
in
10/
10
males
was
observed.
Testicular
and
ovary
weights
were
significantly
reduced
(­
77%
and
­
42%,
respectively);
relative
weights
were
also
reduced
(
by
­
54%
and
­
32%,
respectively).
At
4.63%,
all
animals
on
study
died
between
weeks
1­
5
and
were
reported
to
be
in
poor
condition,
including
rapid
respiration,
swollen
paws,
coarse
fur,
hunched
position
and
unsure
gait,
bloody
nasal
discharge,
inflamed
eyes
and
emaciation.
Histopathological
examination
was
not
performed
on
the
high
dose
animals
due
to
autolysis.
The
LOAEL
is
1.54%
(
1057
mg/
kg/
day
test
material;
125
mg/
kg/
day
boron
equivalents),
based
on
decreased
body
weight,
clinical
signs
and
testicular
atrophy.
The
NOAEL
is
0.463%
(
339
mg/
kg/
day
test
material;
42
mg/
kg/
day
boron
equivalents).

This
90­
day
oral
toxicity
study
in
the
rat
is
classified
as
acceptable
(
non­
guideline).
Although
the
study
was
not
conducted
according
to
standard
Agency
guidelines
(
lacking
clinical
chemistry
and
hematology
data)
and
the
data
suggest
a
possible
dosing
error
or
group
mixup
in
low­
dose
males
in
the
first
weeks,
the
data,
when
taken
together
with
a
second
90­
day
study
in
the
rat
(
MRID
40692306)
and
a
two­
year
rat
study
(
MRID
40692309),
are
considered
adequate
for
regulatory
purposes
and
satisfy
the
guideline
requirement
for
a
90­
day
oral
toxicity
study
(
OPPTS
870.3100;
OECD
408)
in
the
rat.
A
new
study
is
not
required
at
this
time.

(
2)
In
a
subchronic
oral
toxicity
study
(
MRID
00068025),
boric
acid
(
technical
grade,

$
98.97%
a.
i.)
was
administered
to
10
Charles
River
Sprague­
Dawley
rats/
sex/
dose
at
dietary
Page
70
of
84
concentrations
of
0,
0.03,
0.1,
0.3,
1.0
or
3.0%
(
equivalent
to
average
daily
intakes
of
0,
3.9,
12.8,
38.0,
123.6
or
500
mg/
kg/
day
boron
equivalent).

At
0.3%,
one
male
showed
complete
atrophy
of
about
1/
3
of
the
tubules
(
not
used
to
determine
LOAEL
based
on
single
finding).
At
1.0%,
clinical
signs
of
toxicity
beginning
at
week
3
(
hunched
posture,
labored
breathing,
piloerection,
desquamation,
inflames
eyes,
swollen
paws),
significantly
reduced
mean
body
weight
(
at
termination,
­
42%
less
than
controls
for
males
and
­
15%
below
controls
for
females),
reduced
testicular
size
in
all
males,
markedly
reduced
mean
abs/
rel
testicular
weights
(­
76%/­
56%
less
than
controls),
complete
atrophy
of
the
testes
with
increased
epithelial
cells
(
all
males),
reduced
mean
abs/
rel
ovarian
weights
(­
27%/­
20%)
with
no
microscopic
correlates.
Males
showed
a
slight
increase
in
lipid
content
and
cell
size
of
the
adrenal
zona
reticularis.
At
3.0%,
excessive
toxicity
was
observed
in
all
animals
(
hunched
position,
desquamation
of
skin
on
tail
and
paws,
rapid/
labored
breathing,
shrunken
testes,
unsure
gait,
weight
loss)
and
all
animals
died
(
males
by
3
weeks,
females
by
6
weeks).
At
necropsy,
blood
in
the
lungs,
congestion
of
kidneys,
livers
and
adrenals
were
seen
The
LOAEL
is
1.0%
(
123.6
mg/
kg/
day
boron
equivalents),
based
on
decreased
body
weight
in
both
sexes,
testicular
atrophy.
The
NOAEL
is
0.3%
(
38
mg/
kg/
day
boron
equivalents).

This
90­
day
oral
toxicity
study
in
the
rat
is
classified
as
acceptable
(
nonguideline).
Although
the
study
was
not
conducted
according
to
standard
Agency
guidelines
(
lacking
clinical
chemistry
and
hematology
data),
the
data,
when
taken
together
with
a
two­
year
rat
study
(
MRID
00068883),
are
considered
adequate
for
regulatory
purposes
and
satisfy
the
guideline
requirement
for
a
90­
day
oral
toxicity
study
(
OPPTS
870.3100;
OECD
408)
in
the
rat.
A
new
study
is
not
required
at
this
time.

(
3)
In
a
subchronic
oral
toxicity
study
(
MRID
40692306),
sodium
tetraborate
decahydrate
(
borax
technical,
analyzed
at
about
105%
of
theoretical)
was
administered
to
10
male
Charles
River
Sprague
Dawley
rats/
dose
in
the
diet
at
dose
levels
of
0,
0.0154%,
0.0463%,
0.154%
or
0.463%
(
equivalent
to
0,
11.7,
35.5,
115
or
362
mg/
kg/
day
test
material;
0,
1.3,
4.3,
13.1
or
41
mg/
kg/
day
boron
equivalents)
for
13
weeks.
Clinical
chemistries
(
blood,
urine),
hematology
and
ophthalmologic
evaluations
were
not
performed.

There
were
no
treatment­
related
effects
observed
on
clinical
signs,
mortality,
body
weight/
weight
gain,
food
consumption,
organ
weights
or
gross/
microscopic
pathology
at
any
dose
tested.
The
NOAEL
for
systemic
toxicity
in
male
rats
is
0.463%
(
41
mg/
kg/
day
elemental
boron).
A
LOAEL
was
not
determined
in
this
study.

This
90­
day
oral
toxicity
study
in
the
rat
is
classified
as
acceptable
(
nonguideline).
The
study
was
conducted
using
only
males
and
numerous
parameters
were
not
examined.
It
does
not
on
its
own
satisfy
the
guideline
requirement
for
a
90­
day
oral
toxicity
study
(
OPPTS
870.3100;
OECD
408)
in
the
rat.
However,
it
provides
useful
information
to
supplement
a
second
90­
day
rat
subchronic
study
on
borax
(
MRID
40692306)
and
support
selection
of
a
subchronic
NOAEL
Page
71
of
84
in
the
rat
(
42
mg/
kg/
day
boron
equivalents)
and
may
be
used
for
regulatory
purposes.

(
4)
In
a
subchronic
oral
toxicity
study
(
MRID
00064203),
boric
acid
(
purity
not
specified
in
this
report;
batch
received
same
date,
Oct.
12,
1961,
as
batch
used
in
chronic
dog
studies
from
same
laboratory
having
purity
$
99.94%)
was
administered
in
the
diet
to
5
beagle
dogs/
sex/
dose
for
90
days
at
dietary
concentrations
of
0,
0.01,
0.1
or
1.0%
(
equivalent
to
average
daily
intakes
of
0,
0.46,
4.2
or
35
mg/
kg/
day
boron
equivalent).

At
0.1%,
males
showed
artifactual
distortion
of
the
outer
third
of
the
testes
and
lower
testes
weights
(
abs
/
rel.
14.3
g/
0.15%
vs.
17.2
g/
0.20%,
controls).
Because
this
was
apparently
an
artifact
of
fixation,
did
not
appear
to
have
affected
spermatogenesis
and
was
not
seen
in
the
2
year
dog
study
at
comparable
doses,
it
was
not
used
to
establish
the
LOAEL.
Similarly,
appearance
of
squamous
metaplasia
in
the
thyroids
of
2
males
was
not
seen
in
other
studies
at
similar
boron
concentrations
and
was
not
considered
treatment­
related.
Slight
changes
in
the
adrenal
glands
of
females
(
better
developed
reticularis)
were
not
considered
to
be
adverse.
At
1.0%,
males
showed
a
significant
reduction
in
mean
abs/
rel
testes
weight
(
10.4
g/
0.12%
vs.
17.2
g/
0.20%,
controls)
and
severe
testicular
atrophy
in
all
males,
with
complete
degeneration
of
the
spermatogenic
epithelium
in
4/
5
males.
Abs/
rel
liver
weights
in
females
were
significantly
increased
(
345
g/
4.1%
vs
235
g/
2.5%)
but
no
correlating
microscopic
findings
were
reported
and
increased
width
of
the
adrenal
zona
reticularis
and
glomerulosa
was
reported.
There
were
no
apparent
treatment­
related
effects
on
survival,
clinical
symptoms,
nor
clear
effects
on
body
weights
(
one
mid
and
one
high
dose
female
showed
body
weight
fluctuations,
which
appeared
to
be
secondary
to
poor
acceptance
of
the
test
diet),
hematology,
clinical
chemistry
parameters
or
gross
pathology.
The
LOAEL
is
1.0%
boric
acid
(
35
mg/
day
boron
equivalents),
based
on
testicular
atrophy.
The
NOAEL
is
0.1%
boric
acid
(
4.2
mg/
kg/
day
boron
equivalents).

This
study
is
classified
as
acceptable
(
nonguideline)
and
satisfies
the
guideline
requirement
for
a
90­
day
oral
toxicity
study
in
the
dog
(
OPPTS
870.3150;
OECD
409)
when
considered
together
with
38­
week
and
2­
year
dietary
dog
studies
on
boric
acid.
It
was
not
conducted
according
to
current
standard
study
guideline
procedures­
several
clinical
chemistry
parameters
were
not
examined
and
histopathological
examination
was
missing
some
tissues.
Furthermore,
artifactual
effects
in
mid
dose
male
testes
complicated
interpretation
of
the
data.
However,
it
is
considered
to
be
acceptable
for
regulatory
purposes
in
consideration
with
the
chronic
studies.

(
5)
In
a
38­
week
oral
toxicity
study
(
MRID
00005624),
boric
acid
(
technical
grade,

$
99.4%
a.
i.)
was
administered
in
the
diet
to
4
beagle
dogs/
sex/
dose
at
concentrations
of
0
or
0.67%
(
equivalent
to
average
daily
dietary
intakes
of
0
or
40
mg/
kg/
day
boron
equivalent,
respectively).
At
week
26,
2
dogs/
sex
dose
were
sacrificed.
At
week
38,
the
remaining
2
control
animals/
sex
and
one
treated
animal/
sex
were
sacrificed.
The
remaining
treated
animals
(
1/
sex)
were
administered
untreated
diet
for
25
days,
then
evaluated
for
recovery.
Hematologic
and
clinical
chemistry
parameters
were
examined
at
week
0,
4,
12,
26
and
38.
Sperm
sample
Page
72
of
84
collection
was
attempted
for
all
males
on
the
study
at
week
26
but
only
a
few
samples
were
successfully
collected.
In
addition,
boron
levels
were
examined
in
blood,
urine
and
feces
collected
throughout
the
study
and
tissue
levels
were
analyzed
at
sacrifice
times.

At
0.67%,
complete
atrophy
of
the
seminiferous
epithelium
was
observed
in
both
males
sacrificed
at
26
weeks,
compared
to
slight
atrophy
in
one
control
male.
At
38
weeks,
both
the
control
and
treated
male
showed
testicular
atrophy
and
arrest
of
spermiation,
although
effects
were
more
severe
in
the
treated
male.
The
male
retained
on
the
untreated
diet
for
an
additional
25
days
did
not
show
testicular
effects,
suggesting
reversibility
may
occur.
There
were
no
apparent
treatment­
related
effects
on
survival,
clinical
signs
of
toxicity,
body
weight.
Sperm
collection
at
week
26
resulted
either
in
no
sample
obtained
or
no
sperm
seen
(
variable
sperm
counts
were
seen
in
3
control
males,
with
no
sample
obtained
from
one).
Boron
balance
studies
indicated
that
there
was
not
significant
accumulation
in
tissues.
Urinary
levels
were
increased
but
boron
was
excreted
out
within
a
few
days
of
stopping
the
test
diet.
The
systemic
toxicity
LOAEL
is
0.67%
(
40
mg/
kg/
day
boron
equivalents),
based
on
testicular
atrophy
and
arrest
of
spermiation.
The
NOAEL
was
not
determined
since
only
a
single
dose
was
tested.

This
chronic
study
in
the
dog
is
classified
acceptable
(
nonguideline)
when
considered
together
with
the
findings
of
a
90­
day
and
a
two­
year
dietary
study
in
the
dog
(
MRIDs
00064203
and
00005622);
by
itself
it
does
not
satisfy
the
guideline
requirement
for
a
chronic
oral
study
[
OPPTS
870.4100,
OECD
452]
in
the
dog.
Only
a
single
dose
was
tested,
a
small
number
of
animals
were
available
for
each
time
point
evaluation,
only
limited
clinical
chemistry
parameters
were
evaluated
and
histopathology
was
not
complete.
At
this
time,
the
data
requirement
for
a
chronic
oral
toxicity
study
in
the
dog
is
considered
to
be
satisfied
and
no
additional
data
are
required.

(
6)
In
a
chronic
oral
toxicity
study
(
MRID
00005622),
boric
acid
(
technical
grade,

$
98.7%
a.
i.)
was
administered
in
the
diet
to
4
beagle
dogs/
sex/
dose
at
concentrations
of
0.033,
0.067
or
0.20%
for
up
to
two
years
(
equivalent
to
average
daily
intakes
of
0,
1.6,
3.6
or
10.2
mg/
kg/
day
boron
equivalents,
males
and
0,
1.8,
4.0
or
11.6
mg/
kg/
day
boron
equivalents,
females).
One
animal/
sex/
dose
group
was
sacrificed
at
12
months
for
interim
evaluation.
At
24
months,
two
control
and
high
dose
animals/
sex
were
sacrificed
and
three
low
and
mid
dose
animals/
sex
were
sacrificed.
The
remaining
control
and
high
dose
animals
were
continued
on
untreated
diet
for
3
months
and
were
sacrificed
at
27
months
to
evaluate
recovery.
Boron
balance
studies
were
also
performed
by
determining
boron
in
blood,
urine
and
feces
at
several
study
intervals
from
control
and
high
dose
dogs.
Tissue
samples
were
also
analyzed
for
boron
at
the
sacrifice
intervals.

Clear
treatment­
related
effects
were
not
observed.
At
12
months
slight
focal
atrophy
of
the
testes
was
seen
at
0.20%.
At
24
months,
one
male
had
complete
testicular
atrophy
but
the
second
male
was
normal.
There
was
slight
testicular
atrophy
in
the
control
and
treated
male
in
the
recovery
group.
Because
of
the
duration
of
the
study,
lack
of
significant
atrophy
at
12
months
Page
73
of
84
and
small
number
of
animals,
the
testicular
atrophy
at
24
months
is
noted,
but
of
uncertain
relationship
to
treatment.
Boron
balance
studies
indicated
that
it
did
not
accumulate
in
tissues,
with
levels
reaching
steady
state
by
1­
2
weeks.
Boron
was
completely
eliminated
by
9
days
after
eliminating
the
test
diet.
The
NOAEL
(
tentative)
is
0.20%
(
10.2
mg/
kg/
day
boron
equivalents).
A
LOAEL
was
not
achieved.

This
chronic
study
in
the
dog
is
classified
as
acceptable
(
nonguideline)
and
satisfies
the
guideline
requirement
for
a
chronic
oral
study
[
OPPTS
870.4100,
OECD
452]
in
the
dog
when
considered
together
with
MRIDs
00005624,
a
38­
week
dietary
dog
study
and
00064203,
a
90­
day
dog
study),
which
together
establish
an
effect
level.
The
study
was
conducted
prior
to
current
guideline
standards
and
is
deficient
in
several
respects
(
small
numbers
of
animals
at
sacrifice
times,
incomplete
clinical
chemistry
parameters
and
histopathology,
etc.).
However,
it
is
considered
acceptable
for
regulatory
purposes
in
conjunction
with
the
other
studies.

(
7)
In
two
independently
performed
reverse
gene
mutation
assays
(
MRID
42038901),
Salmonella
typhimurium
strains
TA
1535,
1536,
1638,
98
and
100
were
exposed
to
boric
acid
(
tech.,
>
99%
a.
i.)
at
concentrations
of
10
to
2500
µ
g/
plate
in
the
presence
or
absence
of
either
4%
or
10%
rat
liver
S9.

There
was
no
evidence
of
either
cytotoxicity
or
mutagenicity
in
any
of
the
tested
strains
under
these
experimental
conditions.
The
test
material
should
have
been
tested
up
to
5000
µ
g/
plate
since
it
is
sufficiently
water
soluble;
however,
the
results
were
in
good
agreement
with
the
published
finding
that
boric
acid,
prepared
in
water
up
to
1820
µ
g/
plate
or
in
DMSO
up
to
10,000
µ
g/
plate,
was
not
cytotoxic
or
genotoxic
in
S.
typhimurium.
The
positive
controls
induced
the
appropriate
responses
in
the
corresponding
strains.

This
study
is
classified
as
acceptable
(
guideline)
and
satisfies
the
guideline
requirement
for
Test
Guideline
OPPTS
870.51001;
OECD
471
for
in
vitro
mutagenicity
(
bacterial
reverse
gene
mutation)
data.
for
a
gene
mutation
study
in
bacteria.

(
8)
In
a
forward
gene
mutation
assay
in
cultured
mammalian
cells
(
MRID
42038902),
mouse
lymphoma
L5178Y
cells
were
treated
with
boric
acid
(
tech.,
>
99%
a.
i.)
at
concentrations
from
1200
to
5000
µ
g/
mL
in
the
presence
and
absence
of
S9
activation.

Boric
acid
did
not
cause
an
increase
in
the
frequency
of
mutant
colonies
under
the
experimental
conditions.
Doses
of
5000
µ
g/
mL
­
S9
and
3500
and
5000
µ
g/
mL
+
S9
were
marginally
cytotoxic.
The
positive
controls
induced
the
appropriate
responses
in
this
assay.

This
study
is
classified
as
acceptable
(
guideline)
and
satisfies
the
guideline
requirement
for
Test
Guideline
OPPTS
870.5300,
OECD
476
for
in
vitro
mutagenicity
(
mammalian
forward
gene
mutation)
data.
Page
74
of
84
(
9)
In
an
unscheduled
DNA
synthesis
assay
in
cultured
primary
rat
hepatocytes
(
MRID
42038903),
cell
cultures
were
incubated
with
boric
acid
(
tech.,
>
99%
a.
i.)
at
concentrations
from
5
to
5000
µ
g/
mL.

No
treatment­
related
increase
in
unscheduled
DNA
synthesis
was
observed
in
these
assays
up
to
cytotoxic
concentrations
of
boric
acid.
The
apparent
increases
in
net
nuclear
grains
and
percentage
of
cells
in
repair
were
due
to
cytotoxicity
(
and
consequently
reduced
cytoplasmic
grain
count)
at
2500,
3800
and
5000
µ
g/
mL
rather
than
increased
DNA
repair.
The
positive
control
induced
an
increase
in
net
nuclear
grain
counts
and
percent
cells
with
$
5
net
nuclear
counts
in
both
trials.

This
study
is
classified
as
acceptable
(
guideline)
and
satisfies
the
guideline
requirement
for
Test
Guideline
OPPTS
870.5550;
OECD
482/
486
for
other
genotoxic
mutagenicity
data.

(
10)
In
an
in
vivo
mammalian
cell
micronucleus
assay,
boric
acid
(
tech.,
>
99%
a.
i.)
was
administered
twice,
separated
by
24
hrs,
by
gavage
in
distilled
water
to
10
Swiss­
Webster
mice/
sex/
dose
at
0,
900,
1800
or
3500
mg/
kg.
Animals
(
5/
sex/
dose)
were
sacrificed
at
24
or
48
hrs
following
the
second
dosing.

There
were
no
signs
of
toxicity
observed
during
the
study
and
no
evidence
of
cytotoxicity
to
the
target
organ.
Boric
acid
was
tested
at
an
adequate
dose
based
on
the
combined
dose
over
24
hrs
(
7000
mg/
kg)
exceeding
the
limit
dose
of
5000
mg/
kg
for
this
assay
(
daily
dose
of
3500
mg/
kg/
day
was
limited
by
physical
properties
of
the
test
material).
The
positive
control
induced
the
appropriate
response.
There
was
not
a
significant
increase
in
the
frequency
of
micronucleated
polychromatic
erythrocytes
in
bone
marrow
after
any
treatment
time.

This
study
is
classified
as
acceptable
(
guideline)
and
satisfies
the
guideline
requirement
for
Test
Guideline
OPPTS
870.5395;
OECD
474
for
in
vivo
cytogenetic
mutagenicity
data.
Page
75
of
84
3.0
ACTIVE
INGREDIENT
RESIDENTIAL
HANDLER
EXPOSURE
Residential
Handler
Inhalation
Risks
Exposure
Scenario
Application
Rate
Application
Rate
Units
Area
Treated
Daily
Units
Inhalation
Unit
Exposure
(
µ
g/
lb
ai)
Inhalation
Exposurea
(
mg/
day)
Inhalation
Doseb
(
mg/
kgday
%
boron
Inhalation
Doseequivalentc
(
mg/
kg­
day)
Inhalation
MOEd
Mixer/
Loader/
Applicator
BORIC
ACID
Applying
Ready
to
Use
Formulations
with
Aerosol
Cans
0.17
lb
ai/
day
1
NA
2400
0.41
0.0058
17.5
0.001
8,800
Mixing/
Loading/
Applying
Dusts
via
Shaker
Can
(
MRID
45333401)
0.02
lb
ai/
ft2
256
ft2/
day
870
4.5
0.064
17.5
0.011
800
Granular
Bait
Dispersed
by
Hand
(
MRID
45250707)
0.2
lb
ai/
day
1
NA
467
0.09
0.0013
17.5
0.00023
38,000
SODIUM
TETRABORATE
DECAHYDRATE
Mixing/
Loading/
Applying
Dusts
via
Shaker
Can
(
MRID
45333401)
0.5
lb
ai/
day
1
NA
870
0.44
0.0062
11.34
0.0007
13,000
SODIUM
TETRABORATE
PENTAHYDRATE
Loading/
Applying
Granulars
via
Spoon
or
Cup
0.0045
lb
ai/
gallon
20,000
gallons
45
4.1
0.058
14.85
0.0086
1,000
Applying
Ready
to
Use
Formulations
via
Pour­
on
(
using
PHED
liquid
mixer/
loader
data)
0.0031
lb
ai/
gallon
200
gallons
1.2
0.00074
0.000011
14.85
0.0000016
5,500,000
SODIUM
TETRABORATE
Exposure
Scenario
Application
Rate
Application
Rate
Units
Area
Treated
Daily
Units
Inhalation
Unit
Exposure
(
µ
g/
lb
ai)
Inhalation
Exposurea
(
mg/
day)
Inhalation
Doseb
(
mg/
kgday
%
boron
Inhalation
Doseequivalentc
(
mg/
kg­
day)
Inhalation
MOEd
Page
76
of
84
Applying
Ready
to
Use
Formulations
via
Trigger­

Pump
Sprayer
(
MRID
44459801)
0.06
lb
ai/
gallon
0.125
gallons
123
0.00092
0.000013
21.49
0.0000028
3,100,000
DISODIUM
OCTABORATE
Mixing/
Loading/
Applying
Emulsifiable
Concentrates
with
a
Paint
Brush
2.72
lb
ai/
gallon
0.264
gallons
284
0.2
0.0029
25.00
0.00073
12,000
DISODIUM
OCTABORATE
TETRAHYDRATE
Mixing/
Loading/
Applying
Emulsifiable
Concentrates
with
Low
Pressure
Handwand
1
lb
ai/
gallon
10
gallons
30
0.3
0.0043
20.96
0.0009
9,800
Mixing/
Loading/
Applying
Emulsifiable
Concentrates
with
a
Paint
Brush
1
lb
ai/
gallon
10
gallons
284
2.8
0.041
20.96
0.0085
1,000
Applying
Ready
to
Use
Formulations
via
Trigger­

Pump
Sprayer
0.23
lb
ai/
gallon
1
gallon
123
0.028
0.0004
20.96
0.000084
100,000
Applying
Dilute
Sprays
to
Decks
1
lb
ai/
gallon
1
gallon
30
0.03
0.00043
20.96
0.00009
98,000
a
Inhalation
Exposure
=
(
Application
rate)*(
Area
treated
daily)*(
Inhalation
unit
exposure)/(
1000).

b
Inhalation
Dose
=
(
Inhalation
exposure)/(
Adult
body
weight).

c
Inhalation
Dose­
equivalent
=
(
Inhalation
dose)
*
(
percent
boron).

d
MOE
=
NOAEL
(
8.8
mg/
kg­
day)/
Inhalation
dose­
equivalent.
Page
77
of
84
4.0
ACTIVE
INGREDIENT
CONSUMER
USE
RESIDENTIAL
EXPOSURE
CEM
Inputs
ID
Number:
Unknown
Product:
Sodium
tetraborate
decahydrate
Chemical
Name:
sodium
tetraborate
decahydrate
Scenario:
General
Purpose
Cleaner
Population:
Adult
Molecular
Weight
(
g/
mole):
381.9
Vapor
Pressure
(
torr):
1e­
06
Weight
Fraction
­
Median
(
unitless):
0.07
Weight
Fraction
­
90%
(
unitless):
0.13
Inhalation
Inputs
Frequency
of
Use
(
events/
yr):
300
Years
of
Use:
57
Mass
of
Product
Used
per
Event
­
Median
(
g):
61.5
Mass
of
Product
Used
per
Event
­
90%
(
g):
123
Inhalation
Rate
During
Use
(
m3/
hr):
0.55
Duration
of
Use
­
Median
(
hours/
event):
0.667
Inhalation
Rate
After
Use
(
m3/
hr):
0.55
Duration
of
Use
­
90%
(
hours/
event):
1.42
Zone
1
Volume
(
m3):
20
Whole
House
Volume
(
m3):
369
Air
Exchange
Rate
(
air
exchanges/
hr):
0.45
Body
Weight
(
kg):
71.8
Activity
Patterns
User:
1111111221542467422744411
Start
Time:
7
Non­
User:
Room
of
Use:
2.
Kitchen
Hour:
0
6
12
18
Dermal
Inputs
Frequency
of
Use
­
Body
(
events/
yr):
300
SA/
BW
­
Body
(
cm2/
kg):
15.6
Amount
Retained
/
Absorbed
to
Skin
(
g/
cm2­
event):
3.6e­
05
Avg.
Time,
LADDpot,
LADCpot
(
days):
2.74e+
04
Avg.
Time,
ADDpot,
ADCpot
(
days):
2.08e+
04
Avg.
Time,
ADRpot,
Cppot
(
days):
1.00e+
00
Page
78
of
84
CEM
Inhalation
Exposure
Estimates
ID
Number:
sodium
tetraborate
decahydrate
Scenario:
General
Purpose
Cleaner
Population:
Adult
Inhalation
Rate
(
m3/
day):
0.55
Years
of
Use
(
years):
57
Body
Weight
(
kg):
71.8
Frequency
of
Use
(
events/
year):
300
Exposure
Units
Result
AT
(
days)

Chronic
Cancer
LADDpot
(
mg/
kg­
day)
1.44e­
03
2.74e+
04
LADCpot
(
mg/
m3)
7.84e­
03
2.74e+
04
Chronic
Non­
Cancer
ADDpot
(
mg/
kg­
day)
1.90e­
03
2.08e+
04
ADCpot
(
mg/
m3)
1.03e­
02
2.08e+
04
Acute
ADRpot
(
mg/
kg­
day)
1.91e­
04
1.00e+
00
Cppot
(
mg/
m3)
2.21e­
03
1.00e+
00
LADD
­
Lifetime
Average
Daily
Dose
(
mg/
kg­
day)
LADC
­
Lifetime
Average
Daily
Concentration
(
mg/
m3)

ADD
­
Average
Daily
Dose
(
mg/
kg­
day)
ADC
­
Average
Daily
Concentration
(
mug/
m3)

ADR
­
Acute
Dose
Rate
(
mg/
kg­
day)
Cp
­
Peak
Concentration
(
mg/
m3)

Note:
75
years
=
2.738e+
04
days
pot
­
potential
dose
Note:
The
general
Agency
guidance
for
assessing
short­
term,
infrequent
events
(
for
most
chemicals,
an
exposure
of
less
than
24
hours
that
occurs
no
more
frequently
than
monthly)
is
to
treat
such
events
as
independent,
acute
exposures
rather
than
as
chronic
exposure.
Thus,
estimates
of
long­
term
average
exposure
like
ADD
or
ADC
may
not
be
appropriate
for
use
in
assessing
risks
associated
with
this
type
of
exposure
pattern.
(
Methods
for
Exposure­
Response
Analysis
for
Acute
Inhalation
Exposure
to
Chemicals
(
External
Review
Draft).
EPA/
600/
R­
98/
051.
April
1998
Page
79
of
84
CEM
Inputs
ID
Number:
Unknown
Product:
sodium
tetraborate
decahydrate
Chemical
Name:
sodium
tetraborate
decahydrate
Scenario:
Laundry
Detergent
Population:
Adult
Molecular
Weight
(
g/
mole):
381.9
Vapor
Pressure
(
torr):
1e­
06
Weight
Fraction
­
Median
(
unitless):
0.01
Weight
Fraction
­
90%
(
unitless):
0.05
Inhalation
Inputs
Frequency
of
Use
(
events/
yr):
312
Years
of
Use:
57
Mass
of
Product
Used
per
Event
­
Median
(
g):
200
Mass
of
Product
Used
per
Event
­
90%
(
g):
400
Inhalation
Rate
During
Use
(
m3/
hr):
0.55
Duration
of
Use
­
Median
(
hours/
event):
0.333
Inhalation
Rate
After
Use
(
m3/
hr):
0.55
Duration
of
Use
­
90%
(
hours/
event):
0.667
Zone
1
Volume
(
m3):
20
Whole
House
Volume
(
m3):
369
Air
Exchange
Rate
(
air
exchanges/
hr):
0.45
Body
Weight
(
kg):
71.8
Activity
Patterns
User:
1111111235542467422744411
Start
Time:
9
Non­
User:
Room
of
Use:
5.
Utility
Room
Hour:
0
6
12
18
Dermal
Inputs
Frequency
of
Use
­
Body
(
events/
yr):
52
SA/
BW
­
Body
(
cm2/
kg):
15.6
Amount
Retained
/
Absorbed
to
Skin
(
g/
cm2­
event):
1.13e­
05
Avg.
Time,
LADDpot,
LADCpot
(
days):
2.74e+
04
Avg.
Time,
ADDpot,
ADCpot
(
days):
2.08e+
04
Avg.
Time,
ADRpot,
Cppot
(
days):
1.00e+
00
Page
80
of
84
CEM
Inhalation
Exposure
Estimates
ID
Number:
sodium
tetraborate
decahydrate
Scenario:
Laundry
Detergent
Population:
Adult
Inhalation
Rate
(
m3/
day):
0.55
Years
of
Use
(
years):
57
Body
Weight
(
kg):
71.8
Frequency
of
Use
(
events/
year):
312
Exposure
Units
Result
AT
(
days)

Chronic
Cancer
LADDpot
(
mg/
kg­
day)
1.91e­
07
2.74e+
04
LADCpot
(
mg/
m3)
1.04e­
06
2.74e+
04
Chronic
Non­
Cancer
ADDpot
(
mg/
kg­
day)
2.52e­
07
2.08e+
04
ADCpot
(
mg/
m3)
1.37e­
06
2.08e+
04
Acute
ADRpot
(
mg/
kg­
day)
5.96e­
06
1.00e+
00
Cppot
(
mg/
m3)
8.33e­
04
1.00e+
00
LADD
­
Lifetime
Average
Daily
Dose
(
mg/
kg­
day)
LADC
­
Lifetime
Average
Daily
Concentration
(
mg/
m3)

ADD
­
Average
Daily
Dose
(
mg/
kg­
day)
ADC
­
Average
Daily
Concentration
(
mug/
m3)

ADR
­
Acute
Dose
Rate
(
mg/
kg­
day)
Cp
­
Peak
Concentration
(
mg/
m3)

Note:
75
years
=
2.738e+
04
days
pot
­
potential
dose
Note:
The
general
Agency
guidance
for
assessing
short­
term,
infrequent
events
(
for
most
chemicals,
an
exposure
of
less
than
24
hours
that
occurs
no
more
frequently
than
monthly)
is
to
treat
such
events
as
independent,
acute
exposures
rather
than
as
chronic
exposure.
Thus,
estimates
of
long­
term
average
exposure
like
ADD
or
ADC
may
not
be
appropriate
for
use
in
assessing
risks
associated
with
this
type
of
exposure
pattern.
(
Methods
for
Exposure­
Response
Analysis
for
Acute
Inhalation
Exposure
to
Chemicals
(
External
Review
Draft).
EPA/
600/
R­
98/
051.
April
1998
Page
81
of
84
CEM
Inputs
ID
Number:
Unknown
Product:
sodium
tetraborate
Chemical
Name:
sodium
tetraborate
Scenario:
Laundry
Detergent
Population:
Adult
Molecular
Weight
(
g/
mole):
201.3
Vapor
Pressure
(
torr):
1e­
06
Weight
Fraction
­
Median
(
unitless):
0.01
Weight
Fraction
­
90%
(
unitless):
0.05
Inhalation
Inputs
Frequency
of
Use
(
events/
yr):
312
Years
of
Use:
57
Mass
of
Product
Used
per
Event
­
Median
(
g):
200
Mass
of
Product
Used
per
Event
­
90%
(
g):
400
Inhalation
Rate
During
Use
(
m3/
hr):
0.55
Duration
of
Use
­
Median
(
hours/
event):
0.333
Inhalation
Rate
After
Use
(
m3/
hr):
0.55
Duration
of
Use
­
90%
(
hours/
event):
0.667
Zone
1
Volume
(
m3):
20
Whole
House
Volume
(
m3):
369
Air
Exchange
Rate
(
air
exchanges/
hr):
0.45
Body
Weight
(
kg):
71.8
Activity
Patterns
User:
1111111235542467422744411
Start
Time:
9
Non­
User:
Room
of
Use:
5.
Utility
Room
Hour:
0
6
12
18
Dermal
Inputs
Frequency
of
Use
­
Body
(
events/
yr):
52
SA/
BW
­
Body
(
cm2/
kg):
15.6
Amount
Retained
/
Absorbed
to
Skin
(
g/
cm2­
event):
1.13e­
05
Avg.
Time,
LADDpot,
LADCpot
(
days):
2.74e+
04
Avg.
Time,
ADDpot,
ADCpot
(
days):
2.08e+
04
Avg.
Time,
ADRpot,
Cppot
(
days):
1.00e+
00
Page
82
of
84
CEM
Inhalation
Exposure
Estimates
ID
Number:
sodium
tetraborate
Scenario:
Laundry
Detergent
Population:
Adult
Inhalation
Rate
(
m3/
day):
0.55
Years
of
Use
(
years):
57
Body
Weight
(
kg):
71.8
Frequency
of
Use
(
events/
year):
312
Exposure
Units
Result
AT
(
days)

Chronic
Cancer
LADDpot
(
mg/
kg­
day)
1.04e­
07
2.74e+
04
LADCpot
(
mg/
m3)
5.65e­
07
2.74e+
04
Chronic
Non­
Cancer
ADDpot
(
mg/
kg­
day)
1.37e­
07
2.08e+
04
ADCpot
(
mg/
m3)
7.43e­
07
2.08e+
04
Acute
ADRpot
(
mg/
kg­
day)
3.23e­
06
1.00e+
00
Cppot
(
mg/
m3)
4.52e­
04
1.00e+
00
LADD
­
Lifetime
Average
Daily
Dose
(
mg/
kg­
day)
LADC
­
Lifetime
Average
Daily
Concentration
(
mg/
m3)

ADD
­
Average
Daily
Dose
(
mg/
kg­
day)
ADC
­
Average
Daily
Concentration
(
mug/
m3)

ADR
­
Acute
Dose
Rate
(
mg/
kg­
day)
Cp
­
Peak
Concentration
(
mg/
m3)

Note:
75
years
=
2.738e+
04
days
pot
­
potential
dose
Note:
The
general
Agency
guidance
for
assessing
short­
term,
infrequent
events
(
for
most
chemicals,
an
exposure
of
less
than
24
hours
that
occurs
no
more
frequently
than
monthly)
is
to
treat
such
events
as
independent,
acute
exposures
rather
than
as
chronic
exposure.
Thus,
estimates
of
long­
term
average
exposure
like
ADD
or
ADC
may
not
be
appropriate
for
use
in
assessing
risks
associated
with
this
type
of
exposure
pattern.
(
Methods
for
Exposure­
Response
Analysis
for
Acute
Inhalation
Exposure
to
Chemicals
(
External
Review
Draft).
EPA/
600/
R­
98/
051.
April
1998.
Page
83
of
84
5.0
INERT
INGREDIENT
CONSUMER
USE
RESIDENTIAL
EXPOSURE
CEM
Inputs
ID
Number:
Unknown
Product:
Boric
Acid
(
inert
ingredient)
Chemical
Name:
Boric
Acid
Scenario:
General
Purpose
Cleaner
Population:
Adult
Molecular
Weight
(
g/
mole):
61.9
Vapor
Pressure
(
torr):
0.0001
Weight
Fraction
­
Median
(
unitless):
0.15
Weight
Fraction
­
90%
(
unitless):
0.15
Inhalation
Inputs
Frequency
of
Use
(
events/
yr):
300
Years
of
Use:
57
Mass
of
Product
Used
per
Event
­
Median
(
g):
61.5
Mass
of
Product
Used
per
Event
­
90%
(
g):
123
Inhalation
Rate
During
Use
(
m3/
hr):
0.55
Duration
of
Use
­
Median
(
hours/
event):
0.667
Inhalation
Rate
After
Use
(
m3/
hr):
0.55
Duration
of
Use
­
90%
(
hours/
event):
1.42
Zone
1
Volume
(
m3):
20
Whole
House
Volume
(
m3):
369
Air
Exchange
Rate
(
air
exchanges/
hr):
0.45
Body
Weight
(
kg):
71.8
Activity
Patterns
User:
1111111221542467422744411
Start
Time:
7
Non­
User:
Room
of
Use:
2.
Kitchen
Hour:
0
6
12
18
Dermal
Inputs
Frequency
of
Use
­
Body
(
events/
yr):
300
SA/
BW
­
Body
(
cm2/
kg):
15.6
Amount
Retained
/
Absorbed
to
Skin
(
g/
cm2­
event):
3.6e­
05
Avg.
Time,
LADDpot,
LADCpot
(
days):
2.74e+
04
Avg.
Time,
ADDpot,
ADCpot
(
days):
2.08e+
04
Avg.
Time,
ADRpot,
Cppot
(
days):
1.00e+
00
Page
84
of
84
CEM
Inhalation
Exposure
Estimates
ID
Number:
Unknown
Scenario:
General
Purpose
Cleaner
Population:
Adult
Inhalation
Rate
(
m3/
day):
0.55
Years
of
Use
(
years):
57
Body
Weight
(
kg):
71.8
Frequency
of
Use
(
events/
year):
300
Exposure
Units
Result
AT
(
days)

Chronic
Cancer
LADDpot
(
mg/
kg­
day)
4.08e­
02
2.74e+
04
LADCpot
(
mg/
m3)
2.22e­
01
2.74e+
04
Chronic
Non­
Cancer
ADDpot
(
mg/
kg­
day)
5.36e­
02
2.08e+
04
ADCpot
(
mg/
m3)
2.92e­
01
2.08e+
04
Acute
ADRpot
(
mg/
kg­
day)
3.10e­
03
1.00e+
00
Cppot
(
mg/
m3)
3.63e­
02
1.00e+
00
LADD
­
Lifetime
Average
Daily
Dose
(
mg/
kg­
day)
LADC
­
Lifetime
Average
Daily
Concentration
(
mg/
m3)

ADD
­
Average
Daily
Dose
(
mg/
kg­
day)
ADC
­
Average
Daily
Concentration
(
mug/
m3)

ADR
­
Acute
Dose
Rate
(
mg/
kg­
day)
Cp
­
Peak
Concentration
(
mg/
m3)