POLY(
HEXAMETHYLENEBIGUANIDE)
HYDROCHLORIDE
(
PHMB)
RISK
ASSESSMENT
FOR
THE
REREGISTRATION
ELIGIBILITY
DECISION
(
OPPTS
248.4000)

February
14,
2005
Case
3122
PC
Code
111801
Office
of
Pesticide
Programs
Antimicrobials
Division
U.
S.
Environmental
Protection
Agency
1200
Pennsylvania
Avenue,
NW
Washington,
DC
20460
TABLE
OF
CONTENTS
1.0
EXECUTIVE
SUMMARY
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4
2.0.
PHYSICAL
AND
CHEMICAL
PROPERTIES
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9
2.1
Chemical
Identification
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9
2.2
Physical/
Chemical
Properties
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10
3.0
HAZARD
CHARACTERIZATION
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11
3.1
Hazard
Profile
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11
3.2
FQPA
Considerations
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18
3.3
Dose­
Response
Assessment
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18
3.4
Endocrine
Disruption
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20
4.0
EXPOSURE
ASSESSMENT
AND
CHARACTERIZATION
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21
4.1
Summary
of
Registered
Uses
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21
4.2
Dietary
Exposure/
Risk
Pathway
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21
4.2.1
Determining
the
Estimated
Dietary
Intake
of
a
Pesticide
Used
as
a
Disinfectant
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22
4.2.2
Determining
the
Estimated
Dietary
Intake
of
a
Pesticide
in
Latex
Adhesives
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4.2.3
Acute
and
Chronic
Dietary
Exposure
Characterization
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24
4.3
Water
Exposure/
Risk
Pathway
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25
4.4
Residential
Exposure/
Risk
Pathway
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25
4.4.1
Residential
Handler
Scenarios
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25
4.4.1.1
Swimming
Pools/
Spas
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25
4.4.1.2
Spraying
an
All­
Purpose
Cleaner
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26
4.4.1.3
Mopping
Floors
with
an
All­
Purpose
Cleaner
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26
4.4.1.4
Wiping
Hard
Surfaces
with
an
All­
Purpose
Cleaner
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26
4.4.2.
Residential
Post­
Application
Exposure
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26
4.4.2.1Exposure
to
PHMB
through
Swimming
Pool
Use
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27
4.4.2.2Exposure
from
General
Purpose
Cleaner
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31
5.0
AGGREGATE
RISK
ASSESSMENTS
AND
RISK
CHARACTERIZATION
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5.1
Acute
Dietary
Risk
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34
5.2
Chronic
Dietary
Risk
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34
5.3
Short­,
Intermediate­
and
Long­
Term
Aggregate
Risk
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35
5.3.1
Short­
and
Intermediate­
Term
Aggregate
Risk
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35
5.3.2
Long­
term
Aggregate
Risk
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37
6.0
CUMULATIVE
EXPOSURE
AND
RISK
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38
7.0
OCCUPATIONAL
EXPOSURE
AND
RISK
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39
8.0
ENVIRONMENTAL
RISK
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42
8.1
Ecological
Hazard
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42
8.2
Environmental
Fate
and
Transport
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43
8.3
Environmental
Exposure
and
Risk
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43
8.4
Endangered
Species
Considerations
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43
9.0
INCIDENT
REPORT
ASSESSMENT
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44
9.1
Incident
Report
Data
Associated
with
Health
Effects
of
PHMB
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44
9.1.1
OPP's
Incident
Data
System
(
IDS)
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45
9.1.2
Poison
Control
Center
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46
9.1.3
California
Data
­
1982
­
1986
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46
9.1.4
National
Pesticide
Telecommication
Network
(
NPTN)
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9.1.5
Published
Scientific
Literature
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46
9.2
Epidemiologic
Studies
Associated
with
Health
Effects
of
PHMB
in
Humans
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9.3
Summary
and
Conclusions
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46
10.0
REFERENCES
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47
Page
4
of
48
1.0
EXECUTIVE
SUMMARY
Poly(
iminoimidocarbonyliminoimidocarbonyliminohexamethylene)
hydrochloride
(
PHMB)
is
an
antimicrobial
used
in
several
types
of
applications,
including
fungicide,
algicide
and
sanitizer
in
swimming
pools,
preservative
for
cut
flowers,
materials
preservative,
and
all­
purpose
cleaner.

Hazard:
The
acute
toxicity
of
PHMB
is
low
for
both
oral
and
dermal
toxicity
(
Toxicity
Category
III
or
IV);
however,
PHMB
is
a
severe
to
moderate
eye
irritant
(
Toxicity
Category
I
or
II)
and
slight
to
moderate
dermal
irritant
(
Toxicity
Category
II
or
IV).
In
addition,
PHMB
causes
moderate
dermal
sensitization
in
guinea
pigs.

Subchronic
toxicity
testing
of
PHMB
in
rats
and
dogs
showed
no
systemic
toxicity,
but
severe
dermal
irritation
was
evident
in
a
21­
day
dermal
study
at
high
dose
levels
(
60
mg/
kg
and
200
mg/
kg).
The
21­
day
dermal
study
did
not
test
the
limit
dose
because
a
severe
dermal
irritation
was
found
at
a
dose
level
of
300
mg/
kg
in
a
preliminary
study.
In
a
15­
day
inhalation
toxicity
study
in
albino
rats,
moderate
nasal
irritation
and
rapid
breathing
were
observed,
as
were
lung
lesions
and
reduction
in
cortical
thickness
of
the
thymus
in
3/
4
rats
of
each
sex.
A
definitive
NOAEL
or
LOAEL
could
not
be
assigned
based
on
lack
of
reported
details
in
this
study,
but
it
suggests
that
PHMB
toxicity
by
the
inhalation
route
occurs
at
lower
doses
than
the
oral
route.

In
a
developmental
toxicity
study
in
rabbits
(
MRID
42865901),
maternal
toxicity
in
the
form
of
clinical
toxicity
and
increased
mortality
was
observed
at
a
dose
of
40
mg/
kg/
day.
Reduced
numbers
of
litters
and
skeletal
abnormalities
were
observed
in
offspring
at
this
dose.
The
developmental
effects
occurred
only
at
doses
producing
maternal
toxicity.
In
a
developmental
toxicity
study
in
rats
(
cited
in
HED
document
003810),
maternal
toxicity
in
the
form
of
reduced
body
weight
and
food
consumption
was
observed
at
doses
of
86.2
and
172.4
mg/
kg/
day.
Extra
ribs
were
observed
in
fetuses
at
the
higher
dose
level.
In
a
developmental
toxicity
study
in
mice
(
cited
in
HED
document
003810),
reduced
maternal
weight
gain
was
noted
at
a
dose
of
40
mg/
kg/
day.
No
effects
on
offspring
were
noted
in
this
study.
In
a
two­
generation
reproduction
toxicity
study
(
MRID
43617401),
decreased
body
weight
and
food
efficiency
were
observed
in
parental
animals
at
a
dose
of
approximately
250
mg/
kg/
day.
There
were
no
detrimental
effects
of
treatment
with
PHMB
on
reproduction
in
this
study.
Overall,
the
data
on
developmental
and
reproductive
toxicity
of
PHMB
showed
no
increased
susceptibility
of
offspring
to
the
developmental
or
reproductive
effects
of
PHMB.

A
chronic
toxicity
study
conducted
in
rats
(
MRID
44059301)
showed
decreased
body
weight
at
the
high
dose
of
126
mg/
kg/
day
in
males
and
163
mg/
kg/
day
in
females.
Liver
effects
were
also
noted
at
this
dose,
which
included
increased
alkaline
phosphatase
activity
in
females
and
liver
hepatocyte
fat
and
spongiosis
in
males
at
the
high
dose.
In
a
chronic
toxicity
study
in
dogs
(
MRID
43620501),
liver
effects
in
male
and
female
dogs
were
noted
at
the
high
dose
of
91
mg/
kg/
day
and
included
increased
alanine
aminotransferase
and
microscopic
changes
in
the
liver
of
male
dogs.
Testicular
effects
were
noted
in
male
dogs
at
this
dose,
which
included
decreased
testis
weight
and
testicular
tubular
degeneration.
Page
5
of
48
Carcinogenicity
studies
of
PHMB
conducted
in
rats
and
mice
showed
evidence
of
carcinogenicity.
In
female
rats,
vascular
tumors
in
the
form
of
liver
hemangiomas
and
hemangiosarcomas
were
increased
in
a
dose­
related
manner.
In
mice,
significant
trends
were
observed
for
hemangiomas,
hemangiosarcomas,
and
combined
incidence
of
these
tumors.
In
a
dermal
carcinogenicity
study,
in
which
four
groups
of
specific
pathogen
free
(
50M
+
50F)
Alderley
Park
Mice
received
dermal
doses
of
0.3ml
of
0
(
solvent
in
ethanol),
0.6mg
(
0.2%
PHMB
in
ethanol),
6.0mg
(
2%
PHMB
in
ethanol)
and
30.0mg
(
10%
PHMB
in
ethanol)
per
day
for
five
days
a
week
for
80
weeks),
increasing
trends
were
observed
for
liver
angiosarcomas
and
vascular
tumors
from
all
sites
combined.
In
accordance
with
the
EPA
Draft
Guidelines
for
Carcinogen
Risk
Assessment
(
1999),
the
Health
Effects
Division's
Cancer
Assessment
Review
Committee
classified
PHMB
as
"
Suggestive
Evidence
of
Carcinogenicity,
but
Not
Sufficient
to
Assess
Human
Carcinogenic
Potential"
by
the
oral
and
dermal
routes.
Quantification
of
human
cancer
risk
is
not
required.

There
was
no
evidence
of
neurotoxicity
from
any
of
the
available
studies
submitted
for
PHMB.
The
decreased
activity,
stiff/
splayed
gait
and
slight
tremors
seen
in
one
female
dog
in
the
chronic
dog
toxicity
study
(
MRID
#
43620501)
can
be
attributed,
not
to
neurotoxicity,
but
rather
to
the
general
health
conditions
of
the
animals:
decreased
body
weight;
peeling
of
the
skin
on
the
pads
of
the
paws;
staining
of
paws
and
hocks;
forelimb,
hindlimb,
and
forepaw
abrasions,
scabs,
and
sores;
and
elevated
plasma
alanine
transminase
and
aspartate
transferase
activities
were
also
evident
in
this
dog.
The
HIARC
concluded
that
there
is
not
a
concern
for
neurotoxicity
resulting
from
exposure
to
PHMB.

Bioavailability
and
metabolism
studies
showed
that
the
major
route
of
excretion
of
PHMB
in
rats
is
through
feces.
Metabolite
analysis
of
pooled
urine
from
rats
administered
a
low
molecular
weight
fraction
of
PHMB
at
20
mg/
kg
(
the
fraction
showing
the
greatest
absorption)
revealed
the
presence
of
more
than
one
metabolite
but
identification
was
not
performed
due
to
the
small
amount
sample
available
for
analysis.

In
the
two
meetings
held
on
December
18,
2000
and
January
25,
2001,
the
Health
Effects
Division
(
HED)
Hazard
Identification
Assessment
Review
Committee
(
HIARC)
reviewed
the
recommendations
of
the
toxicology
reviewer
for
PHMB
with
regard
to
the
acute
and
chronic
Reference
Doses
(
RfDs)
and
the
toxicological
endpoint
selection
for
occupational/
residential
exposure
risk
assessments.
The
potential
for
increased
susceptibility
of
infants
and
children
from
exposure
to
PHMB
was
also
evaluated,
as
required
by
the
Food
Quality
Protection
Act
(
FQPA)
of
1996.
On
01/
30/
2003
and
02/
06/
2003,
HIARC
reassessed
toxicological
endpoints
for
RfDs,
the
intermediate­
incidental
oral
exposure
and
long­
term
dermal
exposure
scenarios.
In
addition,
the
relative
dermal
absorption
factor
of
PHMB
when
compared
with
oral
exposure
was
also
discussed.

With
respect
to
the
special
hazard­
based
FQPA
factor,
the
HIARC
concluded
that
the
special
FQPA
hazard
based
safety
factor
could
be
removed
(
i.
e.
1X)
for
PHMB.
The
HIARC
concluded
that
there
is
no
concern
for
developmental
neurotoxicity
resulting
from
exposure
to
Page
6
of
48
PHMB
because
there
is
no
evidence
PHMB
will
induce
neurotoxic
effects.
In
addition,
there
is
no
quantitative
or
qualitative
evidence
of
increased
susceptibility
to
the
fetus
following
in
utero
exposure
in
the
prenatal
developmental
toxicity
studies
or
to
the
offspring
when
adults
are
exposed
in
the
two­
generation
reproductive
study.

AD
considered
potential
dietary
exposure
to
PHMB
residues
in
food
and
water.
When
assessing
acute
and
chronic
(
non­
cancer)
dietary
risk,
AD
considered
potential
dietary
exposure
to
the
U.
S.
population
including
infants
and
children
as
well
as
to
females
13­
50
years,
based
on
the
developmental
toxicity
potential
of
this
active
ingredient.
AD
expresses
dietary
risk
estimates
as
a
percentage
of
the
acute
PAD
(
population­
adjusted
dose)
or
chronic
PAD.
Dietary
exposures
that
are
less
than
100%
of
the
aPAD
or
cPAD
are
below
the
Agency's
level
of
concern.

Acute
Dietary
Risk:
PHMB
is
used
in
two
different
types
of
treatments
for
kitchen
counter
tops
(
liquid
cleaning
product
and
ready­
to­
use
wipe).
Acute
dietary
risk
was
assessed
only
for
the
female
13+
subpopulation,
as
an
endpoint
for
acute
dietary
risk
for
the
general
population
was
not
identified
in
the
hazard
database
for
the
chemical.
AD
has
determined
that,
based
on
the
assumptions
and
models
used,
the
acute
dietary
risk
from
exposure
to
PHMB
does
not
exceed
the
Agency's
level
of
concern
for
the
considered
population.
The
highest
dietary
risk
estimate
is
9%
of
the
acute
PAD,
for
adult
women
exposed
to
liquid
disinfectant.

Chronic
Dietary
Risk:
Without
actual
data,
screening
level
estimates
used
for
the
acute
dietary
risk
analysis
were
used
to
assess
potential
chronic
dietary
exposure
and
risk.
The
risk
analysis
assumes
daily
exposure
from
contact
with
PHMB­
treated
sufaces
that
come
into
contact
with
food.
The
chronic
non­
cancer
dietary
analysis
indicates
no
risks
of
concern.

Drinking
Water
Exposure
and
Risk:
None
of
the
uses
associated
with
PHMB
are
expected
to
impact
either
surface
or
ground
water
resources.
Therefore,
no
drinking
water
assessment
was
performed.

Residential
Exposure:
Calculated
MOEs
(
margins
of
exposure)
were
greater
than
the
target
MOE
(
100)
for
residential
post­
application
exposure
to
adults
and
children
in
swimming
pools,
hand
surface
exposure
to
PHMB
disinfectant,
child
hand­
to­
mouth
ingestion
after
mopping,
and
dermal
exposure
to
children
after
mopping.

Aggregate
Exposure
and
Risk:
For
aggregate
assessments,
the
following
scenarios
were
considered
for
adults
exposed
to
PHMB:
dietary
exposure,
dermal
and
inhalation
exposure
from
liquid
pouring
of
PHMB
swimming
pool
product,
and
dermal
and
incidental
oral
exposure
from
swimming.
Aggregate
exposures
for
children
and
toddlers
included
food
exposure
and
dermal
and
incidental
oral
exposure
from
swimming.
Cleaning
activities
were
not
included
in
the
aggregate
assessment
as
these
activities
were
not
felt
to
reasonably
occur
together
with
the
other
exposure
scenarios.
Further,
aggregation
of
the
residential
exposure
scenarios
associated
with
PHMB
uses
involved
only
short­
and
intermediate­
term
exposures.
Drinking
water
risk
was
not
included
in
aggregate
risk
assessments
as
none
of
the
uses
associated
with
PHMB
are
expected
to
Page
7
of
48
impact
either
surface
or
ground
water
resources.
For
PHMB,
exposures
from
oral,
dermal,
and
inhalation
routes
were
aggregated
based
on
similar
toxicological
effects
occurring
from
these
two
routes
of
exposure.

Short­
term
Aggregate
Risk:
Short­
term
aggregate
risks
from
dermal
exposures
to
PHMB
are
considered
together
using
the
NOAEL
value
of
150
mg/
kg/
day
from
the
80­
week
dermal
carcinogenicity
study
in
mice.
Incidental
oral
risks
were
based
upon
the
NOAEL
of
20
mg/
kg/
day
from
three
co­
critical
developmental
toxicity
studies,
while
inhalation
risk
for
short­
term
only
was
based
upon
the
NOAEL
of
20
mg/
kg/
day
from
the
rabbit
developmental
toxicity
study.

Short­
term
aggregate
risks
for
these
exposures
are
assessed
using
the
Aggregate
Risk
Index
method
as
specified
in
the
OPP
guidance
document
"
General
Principles
for
Performing
Aggregate
Exposure
and
Risk
Assessments"
(
USEPA,
2001).
Using
the
ARI
approach
to
estimate
aggregate
risk,
aggregate
MOEs
were
not
of
concern
for
adult
or
children's
exposures.

Long­
term
Aggregate
Risk:
Long­
term
aggregate
risks
were
not
assessed,
as
none
of
the
residential
exposure
scenarios
is
considered
long­
term.

Occupational
Exposure:
The
following
exposed
populations
have
been
identified:
(
1)
handlers
(
mixers,
loaders,
applicators)
of
PHMB
products;
and
(
2)
individuals
who
are
involved
in
post­
application
or
reentry
activities.
Inhalation
and
dermal
exposures
were
addressed
for
occupational
populations
using
surrogate
data
from
the
Pesticide
Handlers
Exposure
Database
(
PHED),
the
Chemical
Manufacturers
Association
(
CMA,
1992)
and
several
studies
which
relate
to
the
use
patterns
of
PHMB.
Using
surrogate
dermal
and
inhalation
unit
exposure
data,
application
rates
from
labels,
and
EPA
estimates
of
daily
amount
handled,
exposure
and
risks
to
handlers
were
assessed.
At
this
time,
EPA
does
not
foresee
post­
application
exposures
for
the
occupational
uses
of
PHMB.

Based
on
the
use
patterns,
EPA
has
identified
PHMB
products
that
are
used
in
the
following
occupational
use
site
categories
(
USC):

°
Material
Preservatives;
°
Food
Handling/
Storage
Establishments
Premises
and
Equipment;
°
Industrial
Processes
and
Water
Systems;
°
Swimming
Pools;
and
°
Medical
Premises
and
Equipment.

The
exposure
scenarios
assessed
in
each
of
the
Use
Site
Categories
are
listed
in
Table
16.

The
inhalation
and
dermal
exposure
and
risk
assessment
was
conducted
using
labeled
rates
with
standard
use­
information
and
CMA
and/
or
PHED
(
Pesticide
Handlers
Exposure
Database)
Page
8
of
48
unit­
exposure
data.
After
performing
the
exposure
assessment,
EPA
determined
that
the
greatest
potential
for
exposure
appears
to
be
the
inhalation
and
dermal
occupational
scenarios
involving
pour
liquid
for
drilling
muds
(
dermal
MOE
=
74
and
inhalation
MOE
=
370,
target
MOEs
of
100)
and
pour
liquid
for
workover
fluids
(
dermal
MOE
=
74
and
inhalation
MOE
=
370,
target
MOEs
of
100).
In
order
to
achieve
MOEs
above
the
target
level
(
i.
e.,
greater
than
100),
scenarios
involving
drilling
muds
and
workover
fluid
must
use
mitigation
measures
such
as
metering
pump
systems.
Calculated
MOEs
using
the
pump
liquid
scenario
(
i.
e.,
dermal
MOE=
1,600
and
inhalation
MOE
3,300)
are
greater
than
the
target
MOE.
As
the
mitigation
measure
brings
the
inhalation
MOE
above
1,000
(
which
includes
the
additional
10x
route­
to­
route
extrapolation),
no
confirmatory
inhalation
toxicity
study
is
needed.
Tables
17
and
18
summarizes
the
calculation
of
the
MOEs
for
occupational
and
commercial
handlers.

Dermal
and
inhalation
MOEs
for
the
commercial
exposure
scenarios
involving
commercial
pool
operators
pouring
PHMB
liquid
into
multiple
residential
swimming
pools
and
spas
are
greater
than
the
target
MOE
and,
therefore,
are
not
of
concern.
The
commercial
handlers
for
the
medical
premises
did
not
trigger
risks
of
concern
for
the
spray/
mop/
wipe
applications.
The
commercial
uses
are
summarized
in
Table
18.

Environmental
Fate
Assessment:
PHMB
is
stable
hydrolytically
in
the
environment
and
has
a
half­
life
of
more
than
thirty
days.
This
may
be
of
environmental
concern
for
surface
water
contamination.
Studies
for
other
fate
processes
have
not
been
submitted
to
the
Agency.

Ecological/
Environmental
Risk
Assessment:
The
labeled
uses
of
PHMB
are
not
expected
to
result
in
significant
environmental
exposure;
therefore,
adverse
effects
on
terrestrial
and
aquatic
species
are
not
anticipated
when
registered
products
are
used
in
accordance
with
the
label.
The
high
toxicity
of
PHMB
to
freshwater
organisms
is
of
concern
in
the
event
of
a
spill
or
misuse
of
the
product.
Product
labeling
indicates
that
the
chemical
is
toxic
to
fish
and
that
discharge
into
water
should
not
occur
except
in
accordance
with
NPDES
requirements.

Incident
Report
Assessment:
There
are
incidents
that
have
been
reported
associated
with
exposure
to
end­
use
products
containing
PHMB.
Dermal
and
ocular
are
the
primary
routes
of
exposure.
Most
of
the
incidents
are
related
to
irritation
and/
or
allergic
type
reaction.
No
chronic
health
effects
associated
with
PHMB
exposure
were
reported
in
any
of
the
databases
or
in
epidemiologic
studies.

2.0
PHYSICAL/
CHEMICAL
PROPERTIES
CHARACTERIZATION
2.1
Chemical
Identification
Page
9
of
48
Chemical
identification
parameters,
including
chemical
and
common/
trade
names,
CAS
Number,
and
molecular
formula
are
provided
in
Table
1.
Vantocil
IB
and
Vantocil
P
are
both
microbiocides
containing
20%
w/
w
poly(
hexamethylenebiguanide)
hydrochloride.
They
are
registered
with
the
Agency
for
use
as
disinfectants.

Table
1.
Chemical
Identification
Chemical
Name
Poly(
hexamethylenebiguanide)
hydrochloride
Common/
Trade
Names
Vantocil
P/
Vantocil
IB
IUPAC
Name
Poly(
iminoimidocarbonyliminoimidocarbonyliminohexamethylene
hydrochloride
Other
Names
Aqueous
solution
of
poly(
hexamethylenebiguanide)
hydrochloride;
polyhexanide
CAS
Number
27083­
27­
8
32289­
58­
0
Empirical
Formula
(
C8H17N5
.
HCl)
n+
1
n
=
1
­
40,
average
n
value
is
between
10­
13.

Structure
X
­
((
CH2)
3
­
NH
­
C
­
NH
­
C
­
NH
­
(
CH2)
3)
n
­
X
  
  
NH
NH
.
HCl
where
X
=
HCl.
NH2
­
(
CH2)
3
or
X
=
­
(
CH2)
3
­
NH
­
C
­
NH
­
CN
  
NH
or
X
=
­
(
CH2)
3
­
NH
­
C
­
NH2
.
HCl
  
NH
2.2
Physical/
Chemical
Properties
The
physical
and
chemical
properties
of
Vantocil
P
are
shown
in
Table
2.
It
can
be
Page
10
of
48
assumed
that
the
general
physical/
chemical
characteristics
of
Vantocil
IB
are
similar
to,
if
not
the
same
as
Vantocil
P.

Table
2.
Physical/
Chemical
Properties
Color
Very
faint
yellow
Physical
State
Mobile
liquid
Specific
Gravity
1.04
at
20oC
Dissociation
Constant
1.2
±
05
x
10­
1
at
25oC
pH
of
5%
Solution
5.7
Stability
14
days
at
54
±
2oC
Melting
Point
Does
not
melt;
decomposition
onset
205­
210oC
Water
Solubility
40g/
100
g
solution
Solubility
in
Organic
Solvents
°
methanol:
>
26
g/
100g
solvent
°
acetone:
2.7
ppm
°
dichloromethane:
0.2
ppm
°
toluene:
0.2
ppm
°
ethyl
acetate:
0.1
ppm
°
n­
hexane:
0.1
ppm
°
acetonitrile:
0.8
ppm
Octanol­
Water
Partition
Coefficient
2.3
x
10­
3
(
reported
only
for
Vantocil
IB)
Page
11
of
48
3.0
HAZARD
CHARACTERIZATION
3.1
Hazard
Profile
A
detailed
hazard
assessment
for
poly(
hexamethylenebiguanide)
hydrochloride
(
PHMB)
is
presented
in
an
attached
appendix
("
Poly(
hexamethylenebiguanide)
hydrochloride
(
PHMB),
Toxicology
Disciplinary
Chapter
for
the
Reregistration
Eligibility
Decision
Document").
Table
3
presents
the
acute
toxicity
data
for
PHMB.
Table
4
highlights
key
toxicological
studies
for
PHMB.

Acute
Toxicity.
The
acute
toxicity
of
PHMB
is
low
for
both
oral
and
dermal
toxicity
(
Toxicity
Category
III
or
IV);
however,
PHMB
is
a
severe
to
moderate
eye
irritant
(
Toxicity
Category
I
or
II)
and
slight
to
moderate
dermal
irritant
(
Toxicity
Category
II
or
IV).
In
addition,
PHMB
causes
moderate
dermal
sensitization
in
guinea
pigs.

Subchronic
Toxicity.
Subchronic
oral
toxicity
studies
conducted
in
both
rats
and
dogs
showed
no
systemic
effects
after
repeated
oral
administration.
In
rats,
body
weight
was
moderately
reduced
in
males
and
females
at
the
highest
dietary
level
(
250
mg/
kg/
day).
In
addition,
iron
pigments
were
observed
in
the
liver
of
some
females
at
the
250
mg/
kg/
day
level.
However,
no
NOAEL
or
LOAEL
values
were
calculated
due
to
lack
of
detailed
histopathological
data
for
the
125
mg/
kg/
day
treatment
group.
In
dogs,
the
high­
dose
treatment
(
275
mg/
kg/
day)
caused
decreased
body
weight
gain
in
female
dogs
and
slight
hemosiderons
in
two
out
of
four
male
dogs.

In
a
21­
day
dermal
toxicity
study,
no
systemic
toxicity
was
observed
in
rats
at
any
dose
level;
however,
higher
dose
levels
were
not
tested
due
to
severe
dermal
irritation
observed
in
a
preliminary
study
at
a
dose
level
of
300
mg/
kg.
The
21­
day
dermal
study
also
showed
severe
dermal
toxicity
(
erythema,
edema,
and
scabbing)
at
dose
levels
of
60
mg/
kg
and
200
mg/
kg.

In
a
15­
day
inhalation
toxicity
study,
groups
of
four
male
and
female
albino
rats
were
exposed,
nose­
only,
to
atmospheres
of
Vantocil
IB
(
20%
PHMB
in
water)
6
hours/
day,
five
days/
week,
for
3
weeks
at
doses
of
0.025,
0.25,
2.75,
12.5,
and
26
mg/
m3.
It
is
uncertain
whether
the
stated
exposures
were
adjusted
for
the
percentage
of
a.
i.
in
Vantocil.
No
signs
of
toxicity
were
reported
at
the
0.025
mg/
m3
dose
level.
At
the
0.25
mg/
m3
dose
level,
moderate
nasal
irritation
and
rapid
breathing
were
observed,
as
were
lung
lesions
(
unspecified
nature)
and
reduction
in
cortical
thickness
of
the
tymus
in
3/
4
rats
of
each
sex.
A
definitive
NOAEL
or
LOAEL
could
not
be
assigned
based
on
lack
of
reported
details
in
this
study,
but
suggests
that
PHMB
toxicity
by
the
inhalation
route
occurs
at
lower
doses
than
the
oral
route.
A
new
study
would
be
required
to
confirm
this
observation.

Developmental
Toxicity.
In
a
developmental
toxicity
study
in
rats
(
Report
#
CTL/
P/
1262,
1976
cited
in
Report
#
003810,
1978),
maternal
effects
(
decreased
body
weight
and
decreased
food
consumption)
were
observed
at
doses
of
86.2
and
172.4
mg/
kg
PHMB,
while
increased
incidence
of
ribs
in
fetus
was
seen
at
the
172.4
mg/
kg/
day
treatment
group.
Page
12
of
48
In
a
developmental
toxicity
study
in
rabbits
(
MRID
42865901),
PHMB
was
shown
to
produce
maternal
effects
in
the
form
of
increased
mortality
and
clinical
toxicity
(
coldness,
few
to
no
feces,
thin
appearance,
and
subdued
behavior)
in
rabbits
at
a
dose
of
40
mg/
kg/
day.
Developmental
effects
consisted
of
reduced
number
of
litters
and
skeletal
abnormalities
and
occurred
at
the
same
dose
level
(
40
mg/
kg/
day)
as
maternal
effects,
indicating
that
developmental
toxicity
at
the
high
dose
was
related
to
maternal
toxicity.

In
a
developmental
toxicity
study
in
mice
(
cited
in
Report
no.
003810),
maternal
body
weight
was
slightly
but
not
significantly
decreased
at
a
dose
of
40
mg/
kg/
day.
There
was
no
evidence
of
developmental
toxicity
in
this
study.

From
the
available
developmental
toxicity
data,
it
was
concluded
by
the
Health
Effects
Division
Hazard
Identification
Assessment
Review
Committee
that
there
was
no
quantitative
or
qualitative
evidence
of
increased
susceptibility
of
rabbit,
mice
or
rat
fetuses
to
in
utero
exposure
to
PHMB
in
developmental
toxicity
studies.
There
was
also
no
quantitative
or
qualitative
evidence
of
increased
susceptibility
in
multi­
generation
reproduction
study
in
rats.

Reproductive
Toxicity.
In
a
multi­
generation
study
conducted
with
PHMB
technical
(
20.2%
a.
i.),
systemic
toxicity
was
evidenced
as
decreased
group
body
weight
and
food
efficiency
in
F0
rats
at
the
high
dose
level
(
239
mg/
kg/
day
in
males,
249
mg/
kg/
day
infemales).
In
addition,
decreased
epididymis
and
kidney
weight
in
F0
males
was
observed
at
this
level.
No
reproductive
effects
were
evident;
however,
there
was
dose­
related
decrease
in
number
of
pup
deaths
on
days
1­
5
post­
partum
for
both
generations.

Chronic
Toxicity.
PHMB
caused
significant
body
weight
reductions
in
a
chronic/
oncogenicity
study
with
rats.
Multiple
effects
on
the
liver
were
also
observed
at
high
doses
in
male
and
female
rats
fed
a
diet
containing
PHMB.
These
included
increased
activity
of
plasma
alkaline
phosphatase
in
both
sexes
as
well
as
incidences
of
hemangiosarcomas
of
the
liver
in
females.
A
Pathology
Work
Group
(
PWG)
convened
to
confirm
the
diagnoses
of
vascular
neoplasms
concluded
that
these
findings
were
incidental.
However,
evidence
from
a
mouse
oncogenicity
study
and
the
absence
of
hemangiosarcomas
in
control
animals
led
to
the
conclusion
than
PHMB
has
the
potential
to
induce
hemangiosarcomas
in
female
Alpk:
APfSD
rats.

In
a
dog
chronic
toxicity
study,
decreases
in
testis
and
liver
weight
and
microscopic
changes
of
the
liver
were
observed
in
male
dogs
fed
a
high
dose
of
PHMB
(
91
mg/
kg/
day
PHMB).
A
female
dog
exhibited
significant
clinical
signs
of
toxicity
(
decreased
activity,
stiff/
splayed
gait
and
slight
tremors)
and
clinical
chemistry
alterations
at
the
high
dose.

Carcinogenicity.
The
carcinogenicity
of
PHMB
was
reviewed
by
the
Health
Effects
Division's
Cancer
Assessment
Review
Committee
in
April
of
2003.
Carcinogenicity
and
chronic
toxicity
studies
conducted
in
Wistar
rats,
C57B1/
10JfCD­
1/
Alpk
mice,
and
Alderley
Park
mice
were
presented
to
the
committee
for
consideration.
Page
13
of
48
In
the
rat
oral
carcinogenicity
study,
the
CARC
concluded
that
female
rats
showed
a
treatment­
related
response
for
hemangiomas
and
hemangiosarcomas
for
all
sites
combined
at
the
high
dose
of
126
mg/
kg/
day
in
males,
162
mg/
kg/
day
in
females.
In
the
mouse
oral
carcinogenicity
study,
the
CARC
concluded
that
the
vascular
hemangiomas
and
hemangiosarcomas
at
the
high
dose
of
715
mg/
kg/
day
in
males
and
856
mg/
kg/
day
in
females
were
treatment­
related,
but
that
the
high
dose
was
excessive.
At
the
mid
dose
of
167
mg/
kg/
day
(
males)
and
217
mg/
kg/
day
(
females),
hemangiomas
and
hemangiosarcomas
combined
were
also
considered
treatment­
related,
since
the
same
tumor
type
was
observed
in
female
mice
and
in
female
rats.
The
rectal­
anal
junction
squamous
cell
carcinomas
were
considered
treatment­
related
at
the
excessive
high
dose,
but
did
not
contribute
to
the
weight­
of­
the­
evidence,
as
they
were
felt
to
be
the
result
of
local
irritant
effects
of
PHMB.

In
the
mouse
dermal
carcinogenicity
study,
liver
angiosarcomas
and
vascular
tumors
(
all
sites
combined)
were
considered
to
be
equivocal
since
the
tumors
in
this
study
were
only
observed
at
an
excessive
dose
(
750
mg/
kg/
day).

Mutagenicity.
Acceptable
mutagenicity
studies
including
a
microbial
gene
mutation
assay,
micronucleus
assay,
in
vitro
cytogenetic
study,
and
in
vivo/
in
vitro
unscheduled
DNA
synthesis
assay
were
conducted
with
PHMB
at
19.6%
(
a.
i.).
No
mutagenic
response
was
observed
in
these
studies,
including
a
lack
of
clastogenic
responses
in
human
lymphocytes.

Neurotoxicity.
Neurotoxicity
data
were
not
required
since
there
was
no
evidence
of
neurotoxic
effects
by
PHMB.

Metabolism.
Metabolism
studies
showed
that
90%
of
the
test
material
was
excreted
in
the
feces.
The
excretion
pattern
of
low,
mid,
and
high
molecular
weight
fractions
of
PHMB
was
similar.
In
rats
given
10
mg/
kg
PHMB,
liver
concentrations
of
PHMB
in
male
and
female
rats
were
0.18%
and
0.19%
of
the
dose,
respectively.
PHMB
concentrations
in
kidneys
were
0.03%
and
0.04%
of
the
dose
for
males
and
females,
respectively.
Bioavailability
at
the
10
mg/
kg
dose
was
4.7%
for
males
and
3.9%
for
females.
Analysis
of
urine
pooled
from
rats
administered
a
low
molecular
fraction
of
PHMB
at
20
mg/
kg
showed
the
presence
of
more
than
one
metabolite,
but
no
identification
was
possible
due
to
the
small
amount
of
sample
available.

Classification
of
Carcinogenic
Potential.
Based
on
the
weight
of
the
evidence,
the
CARC
concluded,
in
accordance
with
the
EPA
Draft
Guidelines
for
Carcinogen
Risk
Assessment
(
July
1999),
that
PHMB
is
classified
into
the
category
"
Suggestive
Evidence
of
Carcinogenicity,
but
not
Sufficient
to
Assess
Human
Carcinogenic
Potential"
by
the
oral
and
dermal
routes.
Quantification
of
human
cancer
risk
is
not
required.
This
classification
is
mainly
due
to
treatmentrelated
significant
increase
in
vascular
tumors
in
females
via
the
oral
route
at
an
adequate
dose.

Table
3.
Acute
Toxicity
of
PHMB
Page
14
of
48
Product
a.
i.
/
EPA
Reg.
No.
Baquacil
20%
PHMB
/
72674­
19
Baquacil
Ultra
20%
PHMB
/
72674­
22
A­
Breeze
96%
PHMB
/
72674­
32
870.1100
Acute
oral
toxicity
MRID
Tox
Category
LD50
=
2747
mg/
kg
00030330
III
LD50
=
1831mg/
kg
(
M)
LD50
=
1617mg/
kg
(
F)
44940701
III
LD50
=
1049mg/
kg
(
F)

45916505
III
870.1200
Acute
dermal
toxicity
MRID
Tox
Category
LD50
>
2.0
ml/
kg
00065124
III
LD50
>
2000mg/
kg
44940702
III
LD50
>
5000mg/
kg
45916506
IV
870.1300
Acute
inhalation
toxicity
MRID
Tox
Category
waived
LC50
=
1.76mg/
L
44970403
III
waived
870.2400
Acute
eye
irritation
MRIDs
Tox
Category
moderate
irritant
00046789;
00065120
II
moderate
irritant
44963902
II
corrosive
45916508
I
870.2500
Acute
dermal
irritation
MRIDs
Tox
Category
moderate
irritant
00046789;
00065120
II
slight
irritant
44949704
IV
slight
irritant
45916509
IV
870.2600
Skin
sensitization
MRID
moderate
sensitizer
42674201
Moderate
Sensitization
mild
sensitizer
44940705
Table
4.
Toxicity
Profile
of
PHMB
Guideline
No./
Study
Type
MRID
No.
(
year)/
Classification/
Doses
Results
870.3100
90­
Day
oral
toxicity
rodents
00053460
(
1966)
Supplementary
0,
2500,
5000
ppm
NOAEL
and
LOAEL
were
not
established
due
to
inadequate
data.

870.3150
90­
Day
oral
toxicity
in
nonrodents
00053461
(
1966)
Minimum
0,
5500,
11000
ppm
NOAL
=
5500
ppm
LOAEL
=
11,000
ppm
based
on
slight
hemosiderosis
in
males,
decrease
total
body
weight
gain
in
females.
Table
4.
Toxicity
Profile
of
PHMB
Guideline
No./
Study
Type
MRID
No.
(
year)/
Classification/
Doses
Results
Page
15
of
48
870.3200
21/
28­
Day
dermal
toxicity
430477­
01
(
1993)
Core
minimum/
guideline
0,
20,
60,
and
200
mg/
kg/
d
NOAL
=
20
mg/
kg/
day
LOAEL
=
60
mg/
kg/
day
based
on
the
increased
incidence
erythema,
edema,
and
scabbing.

870.3250
90­
Day
dermal
toxicity
Not
required.
Endpoints
for
dermal
non­
cancer
risk
assessment
were
selected
from
the
80­
week
dermal
carcinogeicity
study
in
mice.

870.3465
90­
Day
inhalation
toxicity
An
older
15­
day
inhalation
toxicity
study
was
available,
but
contained
many
deficiencies
to
preclude
an
accurate
assessment.

870.3700a
Prenatal
developmental
in
rodents
00065131
(
1979)
minimum/
guideline
0,
200.
1000,
2000
ppm
0,
17.2,
86.2,
172.4
mg/
kg/
d
Maternal
NOAEL
=
17.2
mg/
kg/
day
LOAEL
=
86.2
mg/
kg/
day
based
on
reduced
body
weight
and
reduced
food
consumption.
Developmental
NOAEL
=
86.2
mg/
kg/
day
LOAEL
=
172.4
mg/
kg/
day
based
on
increased
incidence
of
extra
ribs
in
the
fetuses.

870.3700b
Prenatal
developmental
in
nonrodents
42865901
(
1993)
minimum
0,
10,
20,
40
mg/
kg/
day
Maternal
NOAEL
=
20
mg/
kg/
day
LOAEL
=
40
mg/
kg/
day
based
on
increased
mortality,
reduced
food
consumption,
and
clinical
toxicity.
Developmental
NOAEL
=
20
mg/
kg/
day
LOAEL
=
40
mg/
kg/
day
based
on
reduced
number
of
litters
and
skeletal
abnormalities.

870.3800
Reproduction
and
fertility
effects
43617401(
1995)
acceptable/
guideline
1,
200,
600,
2000
ppm
F0
males
23.0,
69.6,
238.9
mg/
kg/
d
F0
females
25.3,
77.0,
258.2
mg/
kg/
d
F1
male
23.9,
71.3,
249.3
mg/
kg/
d
F1
female
26.1,
79.2,
270.5
mg/
kg/
day
Parental/
Systemic
NOAEL
=
600
ppm
LOAEL
=
2000
ppm
based
on
decreased
body
weight
and
food
efficiency
in
F0
males
and
females
and
decreased
epididymis
and
kidney
weight
in
F0
males.
Reproductive
NOAEL
=
2000
ppm
LOAEL
not
observed.
Offspring
NOAEL
=
2000
ppm
Table
4.
Toxicity
Profile
of
PHMB
Guideline
No./
Study
Type
MRID
No.
(
year)/
Classification/
Doses
Results
Page
16
of
48
870.4100a
Chronic
toxicity
rodents
44059301/
44042801
(
1996)
acceptable/
guideline
0,
200,
600,
2000
ppm
male
0,
12.1,
36.3,
126.1
mg/
kg/
day
female
14.9,
45.3,
162.3
mg/
kg/
day
NOAEL
=
600
ppm
LOAEL
=
2000
ppm
based
on
decreased
survival,
reduced
body
weight,
and
decreased
food
utilization
in
females
and
decreased
body
weight
and
decreased
food
utilization
in
males.

870.4100b
Chronic
toxicity
dogs
43620501
(
1995)
acceptable/
guideline
0,
300,
1500,
4500
ppm
0,
9,
46,
and
91
mg/
kg/
day
for
males,
and
9,
45
and
91
mg/
kg/
day
for
females.
The
4500
ppm
was
reduced
to
3000
ppm
(
91
mg/
kg/
day)
on
week
11­
12.
NOAEL
=
46/
45
mg/
kg/
day
males/
females
LOAEL
=
91
mg/
kg/
day
based
on
changes
in
testis,
liver
weight,
and
testicular
tubular
degeneration
in
males;
clinical
signs
of
toxicity
and
clinical
chemistry
alterations
in
females.

870.4200
Carcinogenicity
rats
(
oral)
44059301/
44042801
(
1996)
acceptable/
guideline
0,
200,
600,
2000
ppm
male
0,
12.1,
36.3,
126.1
mg/
kg/
day
female
14.9,
45.3,
162.3
mg/
kg/
day
NOAEL
=
600
ppm
LOAEL
=
2000
ppm
based
on
decreased
survival,
reduced
body
weight,
and
decreased
food
utilization
in
females
and
decreased
body
weight
and
decreased
food
utilization
in
males.
Vascular
tumors
at
126/
162
mg/
kg/
day
870.4300
Carcinogenicity
mice
(
oral)
44074201(
1996)
acceptable/
guideline
0,
400,
1,200,
4000
ppm
m
55,
167,
715
mg/
kg/
d
f
69,
217,
856
mg/
kg/
d
NOAEL
=
400
ppm
LOAEL
=
1,200
ppm
based
on
decreased
body
weight,
non­
neoplastic
histopathological
changes
in
gall
bladder,
liver,
and
rectal­
anal
junction.
Vascular
tumors
and
rectal­
anal
tumors
at
715/
856
mg/
kg/
day
Table
4.
Toxicity
Profile
of
PHMB
Guideline
No./
Study
Type
MRID
No.
(
year)/
Classification/
Doses
Results
Page
17
of
48
870.4300
Carcinogenicity
mice
(
dermal)
93191028,
00066475,
00104796
(
1990)
acceptable/
nonguideline
0,
15,
150,
and
750
mg/
kg/
day
of
20%
PHMB
solutions.
NOAEL
=
150
mg/
kg/
day
LOAEL
=
750
mg/
kg/
day
based
on
increased
mortality
and
decreased
body
weight
in
male
and
female
mice
receiving
PHMB
(
20%
a.
i.).
Vascular
tumors
at
750
mg/
kg/
day
Gene
Mutation
870.5265
Microbial
gene
mutation
assay
41687004
(
1996)
acceptable
3.3,
10,
33.3,
100,
333.3
µ
g/
plate
No
evidence
of
mutagenic
response
Cytogenetics
870.5395
Micronucleus
Assay
870.5375
Cytogenetic
assay
with
human
lymphocytes
41096901/
41404503
(
1989)
acceptable/
guideline
250,
400
mg/
kg
41404501/
42149905
(
1989)
acceptable/
guideline
5,
25,
50
µ
g/
mL
­
S9
male
25,
100,
187.5
µ
g/
mL
+
S9
female
25,
100,
250
µ
g/
mL
+
S9
No
evidence
of
clastogenic
or
aneugenic
effects
No
evidence
of
clastogenic
effects
Other
Effects
870.5550
Unscheduled
DNA
synthesis
assay
in
rat
hepatocytes
41404502/
42149903
(
1989)
acceptable/
guideline
750,
1500
mg/
kg
No
evidence
of
a
genotoxic
response
870.6300
Developmental
neurotoxicity
Not
required;
no
evidence
of
neurotoxicity,
no
evidence
of
selective
developmental
or
reproductive
toxicity
to
offspring.
Table
4.
Toxicity
Profile
of
PHMB
Guideline
No./
Study
Type
MRID
No.
(
year)/
Classification/
Doses
Results
Page
18
of
48
870.7485
Metabolism
and
pharmacokinetics
435999­
01,
435670­
01,
00077926,
and
00086363
(
1975&
1995)
together
they
are
acceptable/
guideline
200,
2000
ppm
10,100
mg/
kg
Metabolite
analysis
of
pooled
urine
from
rats
administered
a
low
molecular
weight
fraction
of
PHMB
at
20
mg/
kg
(
the
fraction
showing
the
greatest
absorption)
revealed
the
presence
of
more
than
one
metabolite
but
identification
was
not
performed
due
to
the
small
amount
of
sample
available
for
analysis.

3.2
FQPA
Considerations
Under
the
Food
Quality
Protection
Act
(
FQPA),
P.
L.
104­
170,
which
was
promulgated
in
1996
as
an
amendment
to
the
Federal
Insecticide,
Fungicide,
and
Rodenticide
Act
(
FIFRA)
and
the
Federal
Food,
Drug
and
Cosmetic
Act
(
FFDCA),
the
Agency
was
directed
to
"
ensure
that
there
is
a
reasonable
certainty
that
no
harm
will
result
to
infants
and
children"
from
aggregate
exposure
to
a
pesticide
chemical
residue.
The
law
further
states
that
in
the
case
of
threshold
effects,
for
purposes
of
providing
this
reasonable
certainty
of
no
harm,
"
an
additional
tenfold
margin
of
safety
for
the
pesticide
chemical
residue
and
other
sources
of
exposure
shall
be
applied
for
infants
and
children
to
take
into
account
potential
pre­
and
post­
natal
toxicity
and
completeness
of
the
data
with
respect
to
exposure
and
toxicity
to
infants
and
children.
Notwithstanding
such
requirement
for
an
additional
margin
of
safety,
the
Administrator
may
use
a
different
margin
of
safety
for
the
pesticide
residue
only
if,
on
the
basis
of
reliable
data,
such
margin
will
be
safe
for
infants
and
children."

Review
of
available
toxicology
data
indicates
that
PHMB
will
not
cause
a
FQPA
concern
since
there
is
no
evidence
it
will
induce
neurotoxic
effects.
Prenatal
toxicity
studies
did
not
provide
quantitative
or
qualitative
evidence
of
increased
susceptibility
to
fetus
following
in
utero
exposure.
The
multi­
generation
reproductive
study
did
not
provide
evidence
of
increased
susceptibility
to
offspring
when
adults
were
exposed.

3.3
Dose­
Response
Assessment
The
doses
and
toxicological
endpoints
selected
for
various
exposure
scenarios
are
summarized
in
Table
5
below.
Page
19
of
48
Table
5:
Doses
and
Toxicological
Endpoints
Used
in
Exposure
Scenarios
Exposure
Scenario
Dose
Used
in
Risk
Assessment,
UF
Special
FQPA
SF*
and
Level
of
Concern
for
Risk
Assessment
Study
and
Toxicological
Effects
Acute
Dietary
(
Females
13­
50
years
of
age)
NOAEL
=
20
mg/
kg/
day
UF
=
100
Acute
RfD
=
0.2
mg/
kg/
day
FQPA
SF
=
1
aPAD
=
acute
RfD
FQPA
SF
=
0.2
mg/
kg/
day
Rabbit
Developmental
Study
(
MRID
42865901)

LOAEL
=
40
mg/
kg/
day
based
on
reduced
number
of
litters
and
skeletal
abnormalities.

Acute
Dietary
(
General
population
including
infants
and
children)
No
Appropriate
single
dose
effects
can
be
selected
for
general
population
Chronic
Dietary
(
All
populations)
NOAEL=
20
mg/
kg/
day
UF
=
100
Chronic
RfD
=
0.2
mg/
kg/
day
FQPA
SF
=
1
cPAD
=
chronic
RfD
FQPA
SF
=
0.2
mg/
kg/
day
Rabbit
Developmental
Study
(
MRID
#:
42865901)
LOAEL
=
40
mg/
kg/
day
Based
on
the
increased
mortality,
reduced
food
consumption,
and
clinical
toxicity;

Mouse
Developmental
Study
(
Report
No.
CTL/
P/
335,
1977
(
cited
in
Report
No.
003810,
1978.
Section
C­
9))
LOAEL
=
40
mg/
kg/
day;
Based
on
reduced
body
weight
gain;
and
Rat
Developmental
Study
(
Report
No.
CTL/
P/
1262,
1976
(
cited
in
Report
No.
003810,
1978.
Section
C­
11))
LOAEL
=
50
mg/
kg/
day
Based
on
reduced
food
consumption.

Short­
Term
Incidental
Oral
(
1­
30
days)
NOAEL=
20
mg/
kg/
day
UF
=
100
Residential
LOC
for
MOE
=
100
Occupational
=
NA
See
Chronic
RfD
Table
5:
Doses
and
Toxicological
Endpoints
Used
in
Exposure
Scenarios
Exposure
Scenario
Dose
Used
in
Risk
Assessment,
UF
Special
FQPA
SF*
and
Level
of
Concern
for
Risk
Assessment
Study
and
Toxicological
Effects
Page
20
of
48
Intermediate­
Term
Incidental
Oral
(
1­
6
months)
NOAEL=
20
mg/
kg/
day
UF
=
100
Residential
LOC
for
MOE
=
100
Occupational
=
NA
See
Chronic
dietary
endpoint
Short­
Term,
Intermediate­
Term,
and
Long­
Term
Dermal
Exposure
Dermal
(
or
oral)
study
NOAEL=
150
mg/
kg/
day
UF
=
100
Residential
LOC
for
MOE
=
100
Occupational
LOC
for
MOE
=
100
80­
Week
Dermal
Painting
Study
(
MRIDs
00066475
and
00104796)
LOAEL
=
750
mg/
kg/
day
based
on
decreased
body
weight
and
liver
tumors.

Short­
Term
and
Intermediate­

Term
Inhalation
Exposure
No
appropriate
route­
specific
study
was
available.
The
oral
endpoint
of
20
mg/
kg
with
a
Margin
of
Exposure
of
100
(
10x
inter­
species
extrapolation,
10x
intra­
species
variation)
is
used.
An
additional
10x
route­
to­
route
extrapolation
is
used
to
determine
if
a
confirmatory
inhalation
toxicity
study
is
warranted.

Cancer
(
Oral,
dermal,

inhalation)
The
HED
Cancer
Assessment
Review
Committee.
(
CARC)
classified
PHMB
as
"
Suggestive
Evidence
of
Carcinogenicity,
but
not
sufficient
to
Assess
Human
Carcinogenic
Potential"
by
the
oral
and
dermal
routes.
Quantification
of
human
cancer
risk
is
not
required.

Notes:
UF
=
uncertainty
factor,
FQPA
SF
=
FQPA
safety
factor,
NOAEL
=
no
observed
adverse
effect
level,
LOAEL
=
lowest
observed
adverse
effect
level,
PAD
=
population
adjusted
dose
(
a
=
acute,
c
=
chronic)
RfD
=
reference
dose,
LOC
=
level
of
concern,
MOE
=
margin
of
exposure
3.4
Endocrine
Disruption
EPA
is
required
under
the
Federal
Food
Drug
and
Cosmetic
Act
(
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
the
recommendations
of
its
Endocrine
Disruptor
Screening
and
Testing
Advisory
Committee
(
EDSTAC),
EPA
determined
that
there
was
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
has
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).
Page
21
of
48
When
the
appropriate
screening
and/
or
testing
protocols
being
considered
under
the
Agency's
EDSP
have
been
developed,
PHMB
may
be
subjected
to
additional
screening
and/
or
testing
to
better
characterize
effects
related
to
endocrine
disruption.

4.0
EXPOSURE
ASSESSMENT
AND
CHARACTERIZATION
4.1
Summary
of
Registered
Uses
Poly(
iminoimidocarbonyliminoimidocarbonyliminohexamethylene)
hydrochloride
(
PHMB)
is
an
antimicrobial
used
in
several
types
of
applications,
including
as
a
fungicide,
algicide
and
sanitizer
in
swimming
pools,
as
a
preservative
for
cut
flowers,
as
a
materials
preservative,
and
as
an
all­
purpose
cleaner
and
surface
disinfectant.
The
registrant
for
PHMB
has
indicated
that
~
95
percent
of
the
use
of
this
chemical
is
for
pools
and
spas
(
PHMB
SMART
Meeting).
However,
it
should
be
noted
that
there
are
many
registered
use
categories
for
this
chemical
in
addition
to
its
use
in
pools
and
spas.
The
handler
scenarios
considered
in
this
assessment
are
summarized
in
Table
6.
These
scenarios
were
selected
based
on
examination
of
product
labels
describing
uses
for
the
product.

Table
6.
PHMB
Handler
Scenarios
Category
Scenario
Material
Preservatives
Pouring
PHMB
industrial
preservative
into
vats
or
tanks
of
slurry
containing
leather
processing
fluids,
silicones,
adhesives,
mineral
slurries,
textiles,
etc.

Residential
and
Public
Access
Premises
PHMB
is
used
as
a
disinfectant
to
spray,
mop
and
wipe
surfaces
throughout
the
kitchen,
bath
and
other
areas
of
the
house.

Food
Handling/
Storage
Establishments
Premises
and
Equipment
Pouring
PHMB
preservative
into
vats
or
tanks
for
tunnel
pasteurization.

Industrial
Processes
and
Water
Systems
Pouring
or
pumping
PHMB
preservative
into
vats
or
tanks
for
preservation
of
oil
well
injection
fluids,
mud
packer
solutions,
and
workover
solutions.

Swimming
Pools
Pouring
PHMB
preservatives
into
pools
or
spas.

Medical
Premises
and
Equipment
PHMB
is
used
in
a
spray,
wipe
and
mop
to
sterilize
surfaces
as
a
hospital
cleaner
disinfectant
and
medical
equipment.
Disinfectants
are
applied
by
spray,
mopping
and
wiping.

4.2
Dietary
Exposure/
Risk
Pathway
For
the
Reregistration
Eligibility
Decision
(
RED),
the
Agency
has
carried
out
the
dietary
exposure
and
risk
assessments
of
PHMB.
Based
on
a
review
of
product
labels
containing
PHMB,
four
uses
have
been
identified
as
having
the
potential
to
cause
indirect
dietary
exposure
due
to
Page
22
of
48
indirect
food
contact:

°
Tunnel
Pasteurization
°
Disinfectant
on
Counter
Tops
°
Latex
Adhesives
on
Food
Packaging
°
Disinfectant
Cloths
Although
tunnel
pasteurization
has
the
potential
for
causing
indirect
dietary
exposure
to
PHMB,
an
Estimated
Daily
Intake
(
EDI)
has
not
been
calculated
for
this
use.
Tunnel
pasteurization
is
a
method
of
preserving
canned
and
bottled
foodstuffs
after
they
have
been
filled
and
sealed.
As
bottles
or
cans
move
along
a
conveyor,
water
of
gradually
increasing
temperature
is
sprayed
to
pasteurize
the
bottles.
Because
the
bottles
or
cans
are
already
sealed,
the
possibility
of
infiltration
of
this
product
from
tunnel
pasteurization
water
into
the
food
appears
to
be
minimal.
It
is
possible
that
PHMB
residues
could
be
transferred
to
a
person's
hands
after
handling
bottles
or
cans
which
were
pasteurized
in
this
manner,
and
then
ingested
via
hand­
tomouth
contact.
However,
the
risk
associated
with
tunnel
pasteurization
is
expected
to
be
orders
of
magnitudes
lower
than
the
other
scenarios
identified,
and
quantifying
the
risk
would
be
difficult.
Therefore,
no
EDI
has
been
calculated
for
this
scenario.

The
calculated
EDIs
for
the
scenarios
are
shown
in
Table
7.
A
description
of
the
assumptions
used
to
calculate
these
numbers
is
described
in
the
following
two
sections.

Table
7.
Summary
of
Dietary
Assessment
of
PHMB
Scenario
EDI
(
mg/
person/
day)
Adult
Male
Daily
Dose
(
mg/
kg/
day)
a
Adult
Female
Daily
Dose
(
mg/
kg/
day)
b
Child
Daily
Dose
(
mg/
kg/
day)
c
Liquid
Disinfectant
11.2
0.016
0.018
0.074
Wipe
Disinfectant
3.16
0.0045
0.0053
0.021
Latex
Adhesive
5.25x10­
8
7.4x10­
10
8.6x10­
10
3.4x10­
9
a
Adult
Male
Dose
=
EDI/
70
kg
body
weight
b
Adult
Female
Dose
=
EDI/
60
kg
body
weight
c
Child
Dose
=
EDI/
15
kg
body
weight
4.2.1
Determining
Estimated
Daily
Intake
(
EDI)
of
a
Pesticide
Used
as
a
Disinfectant
The
Agency
has
used
the
following
equation
for
estimating
the
Estimated
Daily
Intake
of
PHMB
due
to
its
use
as
a
disinfectant.
This
approach
differs
from
the
FDA
approach.

Equation
1:
EDI
(
mg/
kg/
day)
=
AR
(
wash
soln.
[
mg/
cm2]
x
wt.
fraction
of
wash
soln)
x
MF
(
migration
of
pesticide
into
food)
x
SA
(
surface
area
of
exposure
to
food)/
BW
Page
23
of
48
EDI
=
Estimated
daily
intake
AR
=
Application
rate
SA
=
Surface
area
of
the
counter
tops
etc.
to
which
food
is
exposed,
assume
2000
cm2
MF
=
Fraction
of
pesticide
migration
to
food,
assume
10%
BW
=
70
kg
for
a
male
adult,
60
kg
for
a
feamle
adult,
and
15
kg
for
a
child
Hence,
in
actuality,
the
end
use
concentrations
for
disinfectant
uses
are
0.56%
and
0.158%
respectively:

1.
EDI
for
PHMB
disinfectant
solution
(
0.56%):
Using
Eq.
1:

=
(
mg/
cm2)
x
0.56
%
x
0.10
x
2000
cm2
/
BW
=
1.12/
BW
=
1.12/
70
kg
=
0.016
mg/
kg/
day
for
a
male
adult
=
1.12/
60
kg
=
0.0186
mg/
kg/
day
for
a
female
adult
=
1.12
/
15
kg
=
0.074
mg/
kg/
day
for
a
child
For
the
disinfecting
product
(
3.17%
a.
i.)
as
wettable
Wipex
(
Reg#:
50096­
1),
the
Agency
has
made
the
following
assumption:

°
According
to
the
label
of
the
product,
the
percent
active
(
PHMB)
in
the
wettable
cloth
is
3.17.
The
label
directions
indicate
that
each
cloth
must
be
soaked
with
fresh
water
and
used
twenty
times.
The
Agency
has
assumed
that
each
time
the
cloth
is
used,
equal
amount
of
PHMB
is
used
up.
Hence,
each
time
the
Wipex
is
used
the
percent
of
PHMB
is=
3.17/
20
=
0.158
%.
°
In
addition,
the
Agency
also
assumed
that
wetting
the
cloth
does
not
change
in
the
concentration
of
the
active
ingredient
(
i.
e.,
no
dilution
occurs).

2.
EDI
for
PHMB
wettable
wipe
(
0.158
%),
using
eq.
1:

=
(
mg/
cm2)
x
0.00158
x
0.10
x
2000
cm2
/
BW
=
0.316/
BW
=
0.316/
70
kg
=
0.0045
mg/
kg/
day
for
a
male
adult
=
0.316/
60
kg
=
0.0052
mg/
kg/
day
for
a
female
adult
=
0.316/
15
kg
=
0.0209
mg/
kg/
day
for
a
child
4.2.2
Determining
Estimated
Daily
Intake
(
EDI)
of
a
Pesticide
Used
in
Latex
Adhesives
To
calculate
the
EDI
associated
with
use
of
a
PHMB
product
in
latex
adhesives,
a
number
of
assumptions
have
been
made
based
on
the
FDA
guidelines
(
FDA,
2003b):
Page
24
of
48
°
Default
values
listed
in
the
FDA
guidance
have
been
used
for
the
migration
level,
consumption
factor,
total
food
intake,
and
amount
of
packaging
required
for
food.

°
As
a
conservative
assumption,
it
is
assumed
that
latex
adhesive
represents
10%
of
the
packaging.
Also,
it
is
assumed
that
paper
used
in
food
packaging
weighs
50
mg/
in2.

Based
on
these
assumptions,
the
estimated
daily
intake
is
calculated
to
be
5.25x10­
8
mg/
person/
day.

4.2.3
Acute
and
Chronic
Dietary
Exposure
Characterization
The
dietary
exposure
for
different
populations
is
shown
in
Table
8.
Because
the
exposure
associated
with
latex
adhesives
is
several
orders
of
magnitude
less
than
the
exposure
associated
with
the
countertop
disinfectant,
the
cumulative
dietary
exposure
amounts
are,
for
all
practical
purposes,
the
same
as
the
exposure
to
the
countertop
disinfectant.
These
exposure
values
have
been
compared
with
the
aPad
and
cPad
(
Table
8).
Using
liquid
disinfectants
as
a
worst­
case
expected
exposure
scenario,
the
acute
and
chronic
dietary
risk
is
acceptable,
i.
e.,
below
100%
of
the
cPAD.
The
doses
associated
with
exposure
to
treated
latex
adhesives
were
all
below
the
aPad
and
cPad
and
are
therefore
not
of
concern.

Table
8.
Summary
of
Dietary
Exposure
and
Risk
for
PHMB
Population
Subgroup
Acute
Dietary
Chronic
Dietary
Dietary
Exposure
(
mg/
kg/
day)
a
%
aPAD
b
Dietary
Exposure
(
mg/
kg/
day)
a
%
cPAD
b
Liquid
Disinfectant
Adult
Male
0.016
­­
0.016
8
Adult
Female
0.018
9
0.018
9
Child
0.074
­­
0.074
37
Wipe
Disinfectant
Adult
Male
0.0045
­­
0.0045
2
Adult
Female
0.0053
3
0.0053
3
Child
0.021
­­
0.021
11
Latex
Adhesive
Adult
Male
7.4x10­
10
­­
7.4x10­
10
5.69x10­
7
Adult
Female
8.6x10­
10
4.3x10­
7
8.6x10­
10
6.62x10­
7
Table
8.
Summary
of
Dietary
Exposure
and
Risk
for
PHMB
Population
Subgroup
Acute
Dietary
Chronic
Dietary
Dietary
Exposure
(
mg/
kg/
day)
a
%
aPAD
b
Dietary
Exposure
(
mg/
kg/
day)
a
%
cPAD
b
Page
25
of
48
Child
3.4x10­
10
­­
3.4x10­
10
2.62x10­
6
a
acute
and
chronic
exposure
analysis
based
on
daily
consumption
associated
with
use
of
a
liquid
disinfectant
on
counter
tops
and
exposure
to
food
packages
using
treated
latex
adhesive.
b
%
PAD
=
dietary
exposure
(
mg/
kg/
day)
/
aPAD
or
cPAD,
where
aPAD=
0.2
mg/
kg/
day
(
for
adult
females
only)
and
cPAD=
0.2
mg/
kg/
day
(
for
all
populations)

4.3
Water
Exposure/
Risk
Pathway
None
of
the
uses
associated
with
PHMB
are
expected
to
impact
either
surface
or
ground
water
resources.
Therefore,
no
drinking
water
assessment
was
performed.

4.4
Residential
Exposure/
Risk
Pathway
A
detailed
human
exposure
risk
assessment
for
PHMB
is
provided
in
an
attached
Appendix
("
PHMB
Occupational/
Residential
Exposure
Assessment").
The
summary
of
the
exposures
and
risks
to
the
residential
population
are
presented
below.

4.4.1
Residential
Handler
Scenarios
Based
on
the
use
patterns
of
PHMB,
EPA
has
identified
the
four
major
exposure
scenarios
for
residential
handlers
including:

°
Open
pouring
for
swimming
pools/
spas;
°
Spraying
(
aerosol
and/
or
trigger
pump
sprays)
disinfectants;
°
Mopping
with
disinfectants;
and
°
Wiping
with
disinfectants.

Using
surrogate
unit
exposure
data
from
the
Pesticide
Handlers
Exposure
Database
(
PHED)
and
the
CMA
data
base,
application
rates
from
labels,
and
EPA
estimates
of
daily
amount
handled,
exposure
and
risks
to
residential
handlers
were
assessed.

4.4.1.1
Swimming
Pools/
Spas
PHMB
is
assessed
using
a
typical
residential
swimming
pool
capacity
of
20,000
gallons.
The
pool
is
treated
at
a
maximum
rate
of
50
ppm.
Using
the
maximum
dose
on
the
label,
approximately
1,000
grams
are
used
per
day
(
2.2
lb
ai
per
day)
to
treat
a
residential
pool.
The
assessment
is
based
on
pools
as
representative
of
pools
&
spas.
It
is
assumed
that
a
homeowner
Page
26
of
48
would
apply
PHMB
to
a
pool
by
open
pouring.
The
dermal
and
inhalation
unit
exposures
for
open
pouring
liquid
from
the
CMA
data
base
are
0.135
mg/
lb
ai
and
0.00361
mg/
lb
ai,
respectively
(
based
on
long
pants,
long
sleeved
shirts,
and
no
gloves).
Based
on
these
estimates,
a
homeowner
pouring
PHMB
into
a
single
swimming
pool
does
not
pose
a
risk
of
concern
(
dermal
MOE
=
35,000
and
inhalation
MOE
=
180,000).

4.4.1.2
Spraying
An
All­
Purpose
Cleaner
PHMB
is
used
as
a
general
purpose
cleaner
and
is
assumed
to
be
available
as
either
a
trigger
pump
spray
or
an
aerosol
can.
EPA
used
Reg.
No.
71661­
1
to
estimate
the
amount
sprayed
by
a
homeowner.
This
product
indicates
a
concentration
of
0.56
percent.
At
a
maximum,
it
is
assumed
that
0.5
liter
is
sprayed
during
an
event
and
that
the
product
has
a
density
of
1
g/
mL.
Therefore
the
amount
handled
would
be
2.8
g
ai
or
0.006
lb
ai
per
day.
The
dermal
and
inhalation
unit
exposures
for
an
aerosol
can
from
PHED
are
220
mg/
lb
ai
and
1.3
mg/
lb
ai,
respectively
(
based
on
short
pants,
short
sleeved
shirts,
and
no
gloves).
Based
on
these
estimates,
a
homeowner
spraying
the
cleaner
does
not
pose
a
risk
of
concern
(
dermal
MOE
=
8,000
and
inhalation
MOE
=
180,000).

4.4.1.3
Mopping
Floors
With
An
All­
Purpose
Cleaner
PHMB
is
used
as
a
general
purpose
cleaner
and
is
also
assumed
to
be
available
to
clean
floors
with
a
mop.
EPA
used
Reg.
No.
71661­
1
to
estimate
an
application
rate/
concentration
for
PHMB.
This
product
indicates
a
concentration
of
0.56
percent.
Assuming
that
1­
gallon
mop
bucket
is
used
by
a
resident
to
mop
the
floor,
the
amount
handled
would
be
10.6
gm
ai
or
0.023
lb
ai
per
day.
The
dermal
and
inhalation
unit
exposures
for
mopping
from
CMA
are
71.6
mg/
lb
ai
and
2.38
mg/
lb
ai,
respectively
(
based
on
long
pants,
long
sleeved
shirts,
and
no
gloves).
Based
on
these
estimates,
a
homeowner
mopping
the
floor
does
not
pose
a
risk
of
concern
(
dermal
MOE
=
6,400
and
inhalation
MOE
=
26,000).

4.4.1.4
Wiping
Hard
Surfaces
With
An
All­
Purpose
Cleaner
PHMB
is
used
as
a
general
purpose
cleaner
and
is
also
assumed
to
be
available
to
clean
hard
surfaces
with
a
hand
held
wipe.
A
specific
label
for
the
wipes
was
not
used,
instead
it
is
assumed
that
the
application
rate/
concentration
is
similar
to
that
of
EPA
Reg.
71661­
1.
Assuming
that
0.5
liter
is
used
per
day
for
wiping,
the
amount
handled
would
be
2.8
g
ai
or
0.006
lb
ai
per
day.
The
dermal
and
inhalation
unit
exposures
for
wiping
from
CMA
are
2870
mg/
lb
ai
and
67.3
mg/
lb
ai,
respectively
(
based
on
long
pants,
long
sleeved
shirts,
and
no
gloves).
Based
on
these
estimates,
a
homeowner
wiping
hard
surfaces
does
not
pose
a
risk
of
concern
(
dermal
MOE
=
610
and
inhalation
MOE
=
3,400).

4.4.2
Residential
Post­
Application
Exposure
(
Dermal
and
Incidental
Ingestion)

Based
on
the
use
patterns,
EPA
has
identified
residential
post­
application
exposure
Page
27
of
48
scenarios
for
the
swimming
pool/
spa
use
along
with
the
hard
surface
cleaners.
The
exposure
scenarios
that
are
considered
representative
of
the
high­
end
exposures
associated
with
PHMB
include:

°
Dermal
exposure
and
ingestion
of
PHMB
via
swimming
in
treated
pools
for
adults
and
children.
°
Dermal
contact
and
incidental
ingestion
(
i.
e.,
hand­
to­
mouth
residue
transfer)
resulting
from
toddlers
crawling
on
treated
floors
after
mopping.
While
other
hard
surfaces
may
be
treated
(
e.
g.,
wiping
counter
tops/
sinks),
it
is
believed
that
the
floor
represents
the
high
end
exposure
scenario
for
children's
contact.

Descriptions
of
these
scenarios
are
presented
in
Table
9.

Table
9.
Residential
Exposure
Scenarios
Use
Site
Categories
Scenario
Descriptions
Data
Source
Swimming
Pools
Pools
are
treated
with
PHMB
(
biocide/
sanitizer/
control
growth
of
algae)
Adults
and
children
are
exposed
via
dermal
contact
to
swimming
pool
water
and
ingestion.
Risk
calculations
have
been
performed
for
both
competitive
swimmers
and
non­
competitive
swimmers.
SWIMODEL
Residential
and
Public
Access
Disinfectant
is
applied
on
counter
tops
and
floors
Toddlers
may
have
dermal
contact
with
floors
and
incidentally
ingest
disinfectants
after
mopping.
Residential
SOP
assumptions
4.4.2.1
Exposure
to
PHMB
through
Swimming
Pool
Use
Dermal
Exposure
The
following
equation
was
used
to
develop
dermal
doses:

where:

Dose
=
Daily
dose
for
pools,
(
mg/
kg/
day),
Cw
=
Chemical
concentration
in
pool
water
(
mg/
L),
Kp
=
Permeability
constant
(
cm/
hr),
SA
=
Surface
area
(
cm2),
ET
=
Exposure
time
(
hrs/
day),
Page
28
of
48
CF
=
Conversion
factor
(
0.001
L/
cm3)
BW
=
Body
weight
(
kg).

The
Cw
and
Kp
parameters
are
chemical
specific
values
whereas,
the
remaining
parameters
are
based
on
the
default
values
provided
in
the
SWIMODEL
3.0.
The
PHMB
pool
water
concentration
of
10.4
mg/
L
is
based
on
information
provided
by
the
registrant
(
MRID
44051301)
and
the
permeability
constant
of
5x10­
6
cm/
hr
is
a
measured
value
also
determined
by
the
registrant
(
MRID
44046301).
It
should
be
noted
that
since
the
permeability
constant
provides
estimates
of
an
internal
dose
from
the
dermal
route
of
exposure,
the
oral
toxicity
endpoint
rather
than
the
dermal
toxicity
endpoint
is
used
to
assess
the
risks
from
the
dermal
swimming
route.
The
assumed
surface
area
presented
in
the
SWIMODEL
is
1.82
m2
for
adults,
1.42
m2
for
children
(
age
11­
14
years),
and
1.04
m2
for
children
(
age
7­
10
years).
The
assumed
body
weight
is
70
kg
for
adults,
48
kg
for
children
(
age
11­
14
years),
and
30
kg
for
children
(
age
7­
10
years).
Exposure
time
for
non­
competitive
swimmers
is
based
on
data
provided
in
EPA's
Exposure
Factors
Handbook
(
1997)
whereas
competitive
swimmer
exposure
time
data
are
based
on
the
Agency's
review
of
the
American
Chemistry
Council
(
ACC)
study
(
ACC,
2002).

It
should
be
noted
that
this
exposure
assessment
identifies
short­
term
(
1­
30
days)
and
intermediate­
term
(
1­
6
month)
noncancer
exposure
doses
based
on
the
reported
toxicology
endpoints
for
PHMB.
Because
of
the
shorter
exposure
durations
of
these
toxicological
endpoints,
conservative
event­
based
exposure
assumptions
are
used
to
calculate
upper
bound
daily
dose
estimates.
The
noncancer
doses
are
not
amortized
over
a
lifetime.
For
longer
term
chronic
and
cancer
doses,
exposure
times
and
frequencies
generated
by
ACC
will
likely
be
considered
and
adjusted
in
the
SWIMODEL
in
the
future.

The
dermal
doses
for
competitive
and
non­
competitive
adults,
children
7­
10
yrs,
and
children
11­
14
yrs
are
presented
in
Table
10.
The
parameters
used
to
calculate
the
dermal
exposure
are
also
included
in
this
table.

Table
10.
Parameters
for
Dermal
Swimming
Exposure
and
Dose
Estimate
Dermal
Adult
Child
(
7­
10
yrs)
Child
(
11­
14
yrs)

Type
of
Swimmer
Comp.
Non­
Comp.
Comp.
Non­
Comp.
Comp.
Non­
Comp.

Cw
(
mg/
L)
10.4
10.4
10.4
10.4
10.4
10.4
Kp
(
cm/
hr)
5E­
6
5E­
6
5E­
6
5E­
6
5E­
6
5E­
6
ET
(
hr/
day)
3
5
1
5
2
3
SA
(
cm2)
1.82E4
1.82E4
1.04E4
1.04E4
1.42E4
1.42E4
BW
(
kg)
70
70
30
30
48
48
Page
29
of
48
CF
(
L/
cm3)
0.001
0.001
0.001
0.001
0.001
0.001
Dose
(
mg/
kg/
day)
4.06E­
5
6.76E­
5
1.80E­
5
9.01E­
5
3.08E­
5
4.62E­
5
The
dermal
swimming
route
is
assessed
using
the
oral
NOAEL
of
20
mg/
kg/
day
because
the
SWIMODEL
estimates
an
internal
dose
resulting
from
the
dermal
route.
The
target
MOE
is
100.
The
equation
for
calculating
the
MOE
based
on
the
dermal
route
of
exposure
is
presented
below:

Table
11
presents
the
estimated
dose
from
the
dermal
route
of
exposure
and
the
corresponding
MOEs
based
on
the
oral
endpoint
for
the
swimming
scenarios
for
each
age
group.

Table
11.
Dermal
Dose
and
MOE
for
Residential
Post­
Application
Swimming
Exposure
Use
Type
Scenario
Description
Dose
(
mg/
kg/
day)
Dermal
MOEa
Swimming
Pool
Adult
Competitive
4.06E­
5
490,000
Adult
Non­
Competitive
6.76E­
5
300,000
Child
(
7­
10
yrs)
Competitive
1.80E­
5
1,100,000
Child
(
7­
10
yrs)

Non­
Competitive
9.01E­
5
220,000
Child
(
11­
14
yrs)
Competitive
3.08E­
5
650,000
Child
(
11­
14
yrs)
Non­
Competitive
4.62E­
5
430,000
aMOE
=
NOAEL
(
mg/
kg/
day)/
Dose
(
mg/
kg/
day).
Dermal
dose
for
swimmers
is
an
internal
dose
based
on
the
SWIMODEL
results,
and
therefore,
the
oral
NOAEL
of
20
mg/
kg/
day
is
used.
Target
MOE
=
100
The
calculated
results
for
short­,
intermediate­,
and
long­
term
exposures
and
risks
indicate
that
the
risks
from
the
dermal
route
of
exposure
are
not
of
concern
(
MOE>
100)
for
the
postapplication
scenarios
developed
in
this
assessment.

Ingestion
Page
30
of
48
The
following
equation
was
used
to
develop
ingestion
doses:

where:

Dose
=
Daily
dose
for
pools,
(
mg/
kg/
day),
Cw
=
Chemical
concentration
in
pool
water
(
mg/
L),
IR
=
Ingestion
rate
of
pool
water
(
L/
hr),
ET
=
Exposure
time
(
hrs/
day),
BW
=
Body
weight
(
kg),

The
PHMB
concentration
in
pool
water
is
based
on
information
provided
by
the
registrant
(
MRID
440513­
01).
The
ingestion
rate
used
in
the
SWIMODEL
3.0
is
based
on
the
value
used
in
EPAs
Residential
SOPs
(
USEPA,
2000)
and
an
EPA
pilot
study
as
discussed
in
ACC's
swimmer
survey
(
ACC,
2002).
The
rest
of
the
assumptions
used
in
calculating
the
ingestion
dose
for
competitive
and
non
competitive
adults
and
children
(
7­
10
yrs
and
11­
14
yrs)
are
presented
in
Table
12
and
are
consistent
with
the
assumptions
used
in
the
dermal
assessment.

Table
12.
Parameters
for
Swimming
Ingestion
Exposure
and
Dose
Estimate
Age
Adult
Child
7­
10
yrs
Child
11­
14
yrs
Type
of
Swimmer
Comp.
Non­
Comp.
Comp.
Non­
Comp.
Comp.
Non­
Comp.

Cw
(
mg/
L)
10.4
10.4
10.4
10.4
10.4
10.4
IR
(
L/
hr)
0.0125
0.0125
0.05
0.05
0.025
0.05
ET(
hr/
day)
3
5
1
5
2
3
BW(
kg)
70
70
30
30
48
48
Dose
(
mg/
kg/
day)
0.0056
0.019
0.017
0.087
0.011
0.033
The
equation
for
calculating
the
oral
MOE
is
presented
below:
Page
31
of
48
MOE
values
were
calculated
for
ingestion
of
swimming
pool
water
and
are
presented
in
Table
13.

Table
13.
Ingestion
Dose
and
MOE
for
Residential
Swimming
Post­
Application
Use
Type
Scenario
Description
Dose
(
mg/
kg/
day)
Ingestion
MOE
a
Swimming
Pool
Adult,
Competitive
0.0056
3600
Adult,
Non­
Competitive
0.019
1100
Child
(
7­
10
yrs),
Competitive
0.017
1200
Child
(
7­
10
yrs),
Non­
Competitive
0.087
230
Child
(
11­
14
yrs),
Competitive
0.011
1800
Child
(
11­
14
yrs),
Non­
Competitive
0.033
620
aMOE
=
NOAEL
mg/
kg/
day/
Dose
(
mg/
kg/
day).
Oral
NOAEL
is
20
mg/
kg/
day.
Target
MOE
=
100
The
calculations
for
intermediate
incidental
ingestion
of
PHMB
indicate
no
risk
concern
for
the
non­
competitive
or
competitive
swimming
pool
scenarios.

4.4.2.2
Exposure
from
General
Purpose
Cleaner
(
Floor
Treatments)

Dermal
Contact
(
Toddlers
Crawling
On
Floors
After
Mopping)

There
is
the
potential
for
dermal
exposure
to
toddlers
crawling
on
treated
floors
after
mopping
with
PHMB.
To
determine
toddler
exposure
to
residues
on
treated
floors,
the
following
equation
was
used:

PDD
FR
x
SA
BW
=

where:
PDD
=
Potential
daily
dose
FR
=
Flux
rate
of
chemical
from
material
(
mg/
m2/
day)
SA
=
Surface
area
of
the
body
which
is
in
contact
with
the
floor
(
m2)
BW
=
Body
weight
(
kg)

The
following
conservative
assumptions
were
made
in
calculating
the
exposures/
risks
due
to
limited
data:

°
Toddlers
(
3
years
old)
are
used
to
represent
the
1
to
6
year
old
age
group
and
are
assumed
to
weigh
15
kg,
the
median
for
male
and
female
toddlers
(
USEPA,
2000b).
A
body
surface
area
of
0.657
m2
has
been
assumed,
which
is
the
median
value.
Page
32
of
48
°
The
label
did
not
provide
information
on
the
volume
of
disinfectant
to
be
used
for
cleaning
surfaces
such
as
floors.
It
was
assumed
that
the
diluted
treatment
solution
is
applied
at
a
rate
of
1000
sq.
ft.
per
gallon.
°
No
data
could
be
found
regarding
the
quantity
of
solution/
residue
left
on
the
floor
after
treatment.
As
a
conservative
measure,
it
has
been
assumed
that
25%
of
the
mop
solution
remains
after
the
final
mop.
°
No
leaching
data
were
available
that
could
be
used
to
estimate
a
flux
rate
of
the
chemical
from
the
floor/
hard
surface.
Therefore,
the
Residential
SOPs
estimate
of
10%
of
the
amount
on
the
floor/
hard
surface
available
for
dermal
transfer
is
used.

According
to
label
information
(
EPA
Reg
71661­
1),
this
product
can
be
used
as
a
floor
cleaner
and
contains
0.56%
active
ingredient.
Assuming
that
1
gallon
of
solution
treats
1000
ft2
and
the
density
is
equivalent
to
water
(
1
g/
mL),
the
applied
amount
would
be
227
mg/
m2.
The
SOPs
assume
that
an
average
of
10%
of
the
application
rate
is
available
on
the
hard
surfaces
as
dislodgeable
residues.
Additionally,
it
was
assumed
that
25%
of
the
formulation
remains
on
the
hard
surface.
Therefore,
the
indoor
surface
residue
at
time
zero
would
be
5.68
mg/
m2.
The
SOPs
also
conservatively
assume
that
post­
application
exposure
occurs
immediately
after
application.

The
calculation
of
the
dermal
dose
and
the
dermal
MOE
are
shown
in
Table
14
.
The
dermal
MOE
calculated
is
above
the
target
MOE
of
100
and,
therefore,
not
of
concern.

Table
14.
Short­
and
Intermediate­
term
Risks
Associated
with
Post­
application
Dermal
Exposure
to
Disinfectant
on
Treated
Floors.

Parameter
Value
Rationale
Application
Rate
1gallon
of
solution/
1000
ft2
USEPA
Assumption
%
A.
I.
in
Formulated
Product
0.56%
Maximum
rate
listed
on
label
(
71661­
1)

Density
of
Cleaning
Solution
1.0
g/
mL
Assumed
to
be
similar
to
density
of
water
Flux
Rate
of
Chemical
from
Hard
Surface
Flooring
5.68
mg/
m2/
day
(
App.
Rate)
*(
Density)
*
(%
A.
I.)
*
(
25%
remaining)*
(
10%
transfer)
*
(
Conversion
Factors)

Surface
Area
of
Body
in
Contact
with
Hard
Surface
Flooring
0.657
m2
Median
surface
area
of
toddler
Body
Weight
15
kg
Median
body
weight
of
toddler
Potential
Dermal
Exposure
0.25
mg/
kg/
day
FR
*
SA
*
DA/
BW
Dermal
NOAEL
150
mg/
kg/
day
Table
14.
Short­
and
Intermediate­
term
Risks
Associated
with
Post­
application
Dermal
Exposure
to
Disinfectant
on
Treated
Floors.

Parameter
Value
Rationale
Page
33
of
48
Dermal
MOE
600
(
Derm.
NOAEL)
/
(
Daily
Derm.
Dose).
Target
MOE
=
100.

Incidental
Ingestion
of
PHMB
Resulting
From
Floor
Treatments
(
Hand­
to­
Mouth)

In
addition
to
dermal
exposure,
infants
crawling
on
treated
floors
will
also
be
exposed
to
PHMB
via
incidental
oral
exposure.
To
calculate
incidental
ingestion
exposure
to
PHMB
due
to
hand­
to­
mouth
transfer,
the
scenarios
established
in
the
Standard
Operating
Procedures
(
SOPs)
for
Residential
Exposure
Assessments
were
used.
These
scenarios
use
assumptions
that
are
similar
to
those
used
in
calculating
exposures
due
to
dermal
contact
of
PHMB
from
toddlers
crawling
on
floors
after
mopping.
These
assumptions
level
to
an
estimate
of
0.565
:
g
PHMB/
cm2
being
available
for
dislodging
from
the
floor.
The
estimated
potential
dose
rate
immediately
after
application
would
be
calculated
as
follows:

PDR
norm
=
ISR
t
x
SA
x
FQ
x
SE
x
ET
x
0.001
mg/:
g
BW
where:

PDR
norm
=
Potential
dose
rate
(
mg/
kg/
day);
ISR
t
=
Indoor
surface
residue
(:
g/
cm2)
at
time
0;
SA
=
Surface
area
of
the
hands
that
contact
both
the
treated
area
and
the
individual's
mouth
(
cm2/
event);
FQ
=
Frequency
of
hand­
to­
mouth
events
(
events/
hr);
SE
=
Saliva
extraction
efficiency
(
50%);
ET
=
Exposure
time
(
4
hrs/
day);
and
BW
=
Body
weight
(
15
kg)

The
surface
area
used
for
each
hand­
to­
mouth
event
is
20
cm2
.
It
is
assumed
that
there
are
20
hand­
to­
mouth
exposure
events
per
hour
(
90th
percentile)
for
the
short­
term
and
9.5
events/
hour
(
mean)
for
the
intermediate­
term
duration.
The
PDR
generated
in
this
assessment
is
an
acute
estimate
of
exposure
to
wet
surfaces
only.
In
order
to
calculate
the
short­
term
and
intermediate­
term
dermal
exposure
for
post­
application
dermal
exposures,
the
proposed
data
presented
by
the
Hazard
Identification
Assessment
Review
Committee
(
HIARC)
suggests
that
a
oral
NOAEL
of
20
mg/
kg/
day
should
be
used
as
the
toxicity
endpoint
for
both
short­
and
intermediate­
term
incidental
ingestion
exposures
(
U.
S.
EPA,
2001a).
The
calculation
of
the
potential
dose
rate
(
PDR)
is
0.031
mg/
kg/
day
for
the
short­
term
and
0.014
mg/
kg/
day
for
the
intermediate­
term
duration.
The
resulting
MOEs
for
toddlers
are
660
for
the
short­
term
and
1,400
for
the
intermediate­
term,
which
are
above
the
target
MOE
of
100.
Page
34
of
48
5.0
AGGREGATE
RISK
ASSESSMENTS
AND
RISK
CHARACTERIZATION
In
accordance
with
the
policy
of
the
Office
of
Pesticide
Programs
(
OPP),
aggregate
risk
assessments
are
typically
considered
for
acute
and
chronic
dietary
exposure
(
which
includes
diet
+
drinking
water
exposure)
and
for
short­,
intermediate­,
and
long­
term
exposures,
which
usually
include
the
dietary
exposure
and
any
residential
exposures
that
can
be
thought
of
as
reasonably
occurring
together.
These
aggregate
assessments
can
be
performed
for
both
non­
cancer
and
cancer
as
needed.
In
the
case
of
PHMB,
a
cancer
aggregate
assessment
is
not
needed,
as
the
chemical
has
been
classified
by
OPP's
Cancer
Assessment
Review
Committee
as
having
"
Suggestive
Evidence
of
Carcinogenicity,
but
Not
Sufficient
to
Assess
Human
Carcinogenic
Potential."
For
non­
cancer
aggregate
assessment,
there
is
no
need
for
an
acute
and
chronic
dietary
aggregate
assessment,
as
the
uses
of
PHMB
have
been
determined
to
have
no
impact
on
surface
or
ground
water
and
the
dietary
risk
calculations
estimated
in
this
chapter
will
characterize
the
total
dietary
risk
of
PHMB.
In
the
case
of
short­,
intermediate­,
and
long­
term
aggregate
assessments,
the
following
aggregate
assessments
were
performed
for
adults
exposed
to
PHMB:
dietary
exposure,
dermal
and
inhalation
exposure
from
liquid
pouring
of
PHMB
swimming
pool
product,
and
dermal
and
incidental
oral
exposure
from
swimming.
Aggregate
exposures
for
children
and
toddlers
included
food
exposure
and
dermal
and
incidental
oral
exposure
from
swimming.
Cleaning
activities
were
not
included
in
the
aggregate
assessment
as
these
activities
were
not
felt
to
reasonably
occur
together
with
the
other
exposure
scenarios.
Further,
the
residential
exposure
scenarios
associated
with
PHMB
uses
do
not
involve
long­
term
exposures,
only
short­
and
intermediate­
term
exposures.

For
the
short­
and
intermediate­
term
aggregate
risk
assessment,
the
oral
and
dermal
exposures
were
combined,
due
to
the
common
endpoint
(
decreased
body
weight)
defining
the
toxicity
by
these
two
routes,
in
accordance
with
the
recommendations
of
the
OPP
Hazard
Identification
Assessment
Review
Committee
document.
Oral
exposure
included
both
dietary
and
incidental
oral
exposures,
as
the
study
and
endpoint­
defining
hazards
from
both
dietary
and
incidental
oral
exposures
were
the
same.

5.1
Acute
Dietary
Risk
The
acute
aggregate
risk
assessment
takes
into
account
exposure
estimates
from
dietary
consumption
of
PHMB,
including
food
and
water
exposure.
As
noted,
PHMB
is
not
expected
to
impact
water
exposure.

Acute
aggregate
dietary
risk
from
uses
of
PHMB
supported
in
the
Reregistration
Eligibility
Decision
include
the
liquid
disinfectant
use,
wipe
disinfectant
use,
and
latex
adhesive
use.
As
noted,
the
liquid
disinfectant
use
was
used
as
the
worst­
case
estimate
for
dietary
exposure,
as
simultaneous
use
of
the
wipe
and
liquid
disinfectant
is
not
expected,
and
the
liquid
disinfectant
gives
the
higher
estimate
of
exposure
at
this
time.
Estimated
exposure
from
the
latex
adhesive
use
as
noted
in
the
dietary
exposure
and
risk
section
of
this
chapter
is
negligible
in
comparison
to
the
estimated
exposures
from
the
liquid
and
wipe
disinfectant
uses
and
was
not
Page
35
of
48
included
in
the
aggregate
calculation.
Therefore,
the
acute
aggregate
dietary
risk
is
identical
to
the
risk
from
exposure
to
the
liquid
disinfectant
use.
Acute
dietary
aggregate
risk
calculations
indicate
no
risks
of
concern
for
adult
males
or
females
and
no
risk
of
concern
for
children.

5.2
Chronic
Dietary
Risk
The
chronic
dietary
risk
assessment,
similar
to
that
of
the
acute
assessment,
also
showed
no
risk
of
concern
for
adults
or
children.

5.3
Short­,
Intermediate­,
and
Long­
Term
Aggregate
Risk
These
aggregate
risk
assessments
take
into
account
the
aggregate
exposures
resulting
from
the
dietary
and
residential
exposures
to
PHMB.
As
previously
noted,
included
in
these
assessments
are,
for
adults
exposed
to
PHMB,
dietary
exposure,
dermal
and
inhalation
exposure
from
liquid
pouring
of
PHMB
swimming
pool
product,
and
dermal
and
incidental
oral
exposure
from
swimming.
Aggregate
exposures
for
children
and
toddlers
included
food
exposure
and
dermal
and
incidental
oral
exposure
from
swimming.

5.3.1
Short­
and
Intermediate­
Term
Aggregate
Risk
For
short­
term
and
intermediate­
term
aggregate
risk,
dietary,
incidental
oral,
and
dermal
exposures
were
aggregated
based
on
the
recommendation
of
the
Health
Effects
Division's
HIARC
committee
(
TXR
no.
0051756).
Although
an
oral
toxicity
study
was
selected
for
dietary,
inhalation,
and
incidental
oral
risk
assessments
and
a
dermal
toxicity
study
was
selected
for
dermal
risk
assessments,
the
HIARC
concluded
that
the
non­
cancer
effects
occurring
by
the
oral
and
dermal
routes
were
similar
and
that
these
exposures
should
be
aggregated.
Inhalation
exposures
are
currently
included
in
the
aggregate
assessment
based
on
the
use
of
the
oral
endpoint.
There
is
an
older
15­
day
inhalation
toxicity
study
that
suggests
effects
occurring
by
this
route
differ
from
those
occurring
by
the
dermal
and
oral
route,
but
based
on
the
unacceptability
of
the
inhalation
study
and
the
use
of
the
oral
endpoint,
these
exposures
are
currently
aggregated.
This
could
change
if
an
acceptable
inhalation
toxicity
study
is
submitted
to
confirm
the
observations
noted
in
the
older
15­
day
inhalation
toxicity
study
that
was
available
to
the
Agency
but
which
was
found
to
contain
several
deficiencies.
While
a
target
MOE
of
100
for
inhalation
risk
is
used
in
the
aggregate
risk
calculations,
when
the
extra
10x
uncertainty
factor
was
applied
to
the
inhalation
MOE,
risks
were
still
not
of
concern.
Thus
an
inhalation
toxicity
study
would
not
be
required
at
this
time.
Page
36
of
48
Table
15.
Summary
of
Short­
and
Intermediate­
Term
(
ST
/
IT)
Aggregate
Exposure
and
Risk
Calculations
Population
Subgroup
Chronic
Food
Exp
mg/
kg/
day/

(
MOE)
ST/
IT
Incidental
Oral
Swimming
Exposure
(
mg/
kg/
day)

(
MOE)
ST/
IT
Dermal
Swimming
Exposure
(
mg/
kg/
day)

(
MOE)
Liquid
Pouring
Dermal
Exposure
(
mg/
kg/
day)

(
MOE)
Liquid
Pouring
Inhalation
Exposure
(
mg/
kg/
day)

(
MOE)
Aggregate
Risk
Index
Males
0.016/

(
1250)
0.0056
(
comp.)

(
3600)
0.000044
(
comp.)

(
450,000)
0.00424
(
35,000)
0.000113
(
180,000)
9.0
0.019
(
non­
comp.)

(
1100)
0.000015
(
non­
comp.)

(
1,300,000)
5.7
Females
13­

50
years
0.018/

(
1111)
0.0056
(
comp.)

(
3600)
0.000044
(
comp.)

(
450,000)
0.00491
(
31,000)
0.000131
(
153,000)
8.2
0.019
(
non­
comp.)

(
1100)
0.000015
(
non­
comp.)

1,300,000)
5.4
Children
7­

10
years
0.074/

(
270)
0.017
(
comp.)

(
1200)
0.000018
(
comp.)

(
1,100,000)
N/
A
N/
A
2.2
0.087
(
non­
comp.)

(
230)
0.00009
(
non­
comp.)

(
220,000)
1.2
Children
11­
14
years
0.074
(
270)
0.011
(
1800)
0.00003
(
650,000)
N/
A
N/
A
2.3
0.033
(
620)
0.000046
(
430,000)
1.9
MOE
=
NOEL
(
mg/
kg/
day)/
Dose(
mg/
kg/
day).
Oral
NOAEL
is
20
mg/
kg/
day
for
short­
and
intermediate­
term.
Dermal
NOAEL
is
150
mg/
kg/
day
for
shortand
intermediate­
term.
Inhalation
NOAEL
is
20
mg/
kg/
day
for
short­
term.
The
target
Margins
of
Exposure
for
all
exposures
are
100.

Aggregation
was
performed
using
the
Aggregate
Risk
Index
method.
ARI
=
1/
((
UF1/
MOE1)
+
(
UF2/
MOE2)
+
(
UF3/
MOE3)
+
 ).
ARIs
greater
than
1
are
not
of
concern.
Page
37
of
48
Aggregate
MOE
calculations
for
adults
and
children
were
performed
using
the
Aggregate
Risk
Index
method.
As
shown
in
the
above
table,
no
aggregate
risks
of
concern
were
identified
for
either
adults
or
children.

5.3.2
Long­
term
Aggregate
Risk
A
long­
term
aggregate
risk
assessment
was
not
performed
in
this
assessment.
None
of
the
residential
exposure
scenarios
are
considered
to
be
long­
term
and
were
therefore
not
aggregated
with
the
chronic
dietary
exposure.
Page
38
of
48
6.0
CUMULATIVE
RISK
FQPA
(
1996)
stipulates
that
when
determining
the
safety
of
a
pesticide
chemical,
EPA
shall
base
its
assessment
of
the
risk
posed
by
the
chemical
on,
among
other
things,
available
information
concerning
the
cumulative
effects
to
human
health
that
may
result
from
dietary,
residential,
or
other
non­
occupational
exposure
to
other
substances
that
have
a
common
mechanism
of
toxicity.
The
reason
for
consideration
of
other
substances
is
due
to
the
possibility
that
low­
level
exposures
to
multiple
chemical
substances
that
cause
a
common
toxic
effect
by
a
common
mechanism
could
lead
to
the
same
adverse
health
effect
as
would
a
higher
level
of
exposure
to
any
of
the
other
substances
individually.
A
person
exposed
to
a
pesticide
at
a
level
that
is
considered
safe
may
in
fact
experience
harm
if
that
person
is
also
exposed
to
other
substances
that
cause
a
common
toxic
effect
by
a
mechanism
common
with
that
of
the
subject
pesticide,
even
if
the
individual
exposure
levels
to
the
other
substances
are
also
considered
safe.

AD
did
not
perform
a
cumulative
risk
assessment
as
part
of
this
RED
for
PHMB
because
AD
has
not
yet
initiated
a
review
to
determine
if
there
are
any
other
chemical
substances
that
have
a
mechanism
of
toxicity
common
with
that
of
PHMB.
For
purposes
of
this
RED,
EPA
has
assumed
that
PHMB
does
not
have
a
common
mechanism
of
toxicity
with
other
substances.

On
this
basis,
the
Registrant
must
submit,
upon
EPA's
request
and
according
to
a
schedule
determined
by
the
Agency,
such
information
as
the
Agency
directs
to
be
submitted
in
order
to
evaluate
issues
related
to
whether
PHMB
shares
a
common
mechanism
of
toxicity
with
any
other
substance
and,
if
so,
whether
any
tolerances
for
PHMB
need
to
be
modified
or
revoked.
If
AD
identifies
other
substances
that
share
a
common
mechanism
of
toxicity
with
PHMB,
AD
will
perform
aggregate
exposure
assessments
on
each
chemical,
and
will
begin
to
conduct
a
cumulative
risk
assessment.

The
Health
Effects
Division,
Office
of
Pesticide
Programs,
has
recently
developed
a
framework
proposed
for
conducting
cumulative
risk
assessments
on
substances
that
have
a
common
mechanism
of
toxicity.
This
guidance
was
issued
for
public
comment
on
January
16,
2002
(
67
FR
2210­
2214)
and
is
available
from
the
OPP
Website
at:
http://
www.
epa.
gov/
pesticides/
trac/
science/
cumulative_
guidance.
pdf.
In
the
guidance,
it
is
stated
that
a
cumulative
risk
assessment
of
substances
that
cause
a
common
toxic
effect
by
a
common
mechanism
will
not
be
conducted
until
an
aggregate
exposure
assessment
of
each
substance
has
been
completed.

Before
undertaking
a
cumulative
risk
assessment,
AD
will
follow
procedures
for
identifying
chemicals
that
have
a
common
mechanism
of
toxicity
as
set
forth
in
the
"
Guidance
for
Identifying
Pesticide
Chemicals
and
Other
Substances
that
Have
a
Common
Mechanism
of
Toxicity"
(
64
FR
5795­
5796,
February
5,
1999).
Page
39
of
48
7.0
OCCUPATIONAL
EXPOSURE
AND
RISK
The
following
exposed
populations
have
been
identified:
(
1)
handlers
(
mixers,
loaders,
applicators)
of
PHMB
products;
and
(
2)
individuals
who
are
involved
in
post­
application
or
reentry
activities.
Inhalation
and
dermal
exposures
were
addressed
for
occupational
populations
using
surrogate
data
from
the
Pesticide
Handlers
Exposure
Database
(
PHED),
the
Chemical
Manufacturers
Association
(
CMA,
1992),
and
several
studies
which
relate
to
the
use
patterns
of
PHMB.
Using
surrogate
dermal
and
inhalation
unit
exposure
data,
application
rates
from
labels,
and
EPA
estimates
of
daily
amount
handled,
exposure
and
risks
to
handlers
were
assessed.
At
this
time,
EPA
does
not
foresee
post­
application
exposures
for
the
occupational
uses
of
PHMB.

Handlers
Based
on
the
use
patterns,
EPA
has
identified
PHMB
products
that
are
used
in
the
following
occupational
use
site
categories
(
USC):

°
Material
Preservatives;
°
Food
Handling/
Storage
Establishments
Premises
and
Equipment;
°
Industrial
Processes
and
Water
Systems;
°
Swimming
Pools;
and
°
Medical
Premises
and
Equipment.

The
exposure
scenarios
of
concern
in
each
of
the
USC
are
listed
in
Table
16.

Table
16.
PHMB
Handler
Scenarios
Category
Scenario
Material
Preservatives
Pouring
PHMB
industrial
preservative
into
vats
or
tanks
of
slurry
containing
leather
processing
fluids,
silicones,
adhesives,
mineral
slurries,
textiles,
etc.

Food
Handling/
Storage
Establishments
Premises
and
Equipment
Pouring
PHMB
preservative
into
vats
or
tanks
for
tunnel
pasteurization.

Industrial
Processes
and
Water
Systems
Pouring
or
pumping
PHMB
preservative
into
vats
or
tanks
for
preservation
of
oil
well
injection
fluids,
mud
packer
solutions,
and
workover
solutions.

Swimming
Pools
Pouring
PHMB
preservatives
into
pools
or
spas
by
commercial
treaters.

Medical
Premises
and
Equipment
PHMB
is
used
in
a
spray,
wipe
and
mop
to
sterilize
surfaces
as
a
hospital
cleaner
disinfectant
and
medical
equipment.
Disinfectants
are
applied
by
spray,
mopping
and
wiping.

The
inhalation
and
dermal
exposure
and
risk
assessments
were
conducted
using
labeled
rates
with
standard
use­
information
and
CMA
and/
or
PHED
(
Pesticide
Handlers
Exposure
Page
40
of
48
Database)
unit­
exposure
data.
After
performing
the
exposure
assessment,
EPA
determined
that
the
greatest
potential
for
exposure
appears
to
be
the
inhalation
and
dermal
occupational
scenarios
involving
pour
liquid
for
drilling
muds
(
dermal
MOE
=
74
and
inhalation
MOE
=
370,
target
MOEs
of
100)
and
pour
liquid
for
workover
fluids
(
dermal
MOE
=
74
and
inhalation
MOE
=
370,
target
MOEs
of
100).
In
order
to
achieve
MOEs
above
the
target
level
(
i.
e.,
greater
than
100),
scenarios
involving
drilling
muds
and
workover
fluid
must
use
mitigation
measures
such
as
metering
pump
systems.
Calculated
MOEs
using
the
pump
liquid
scenario
(
i.
e.,
dermal
MOE=
1,600
and
inhalation
MOE
3,300)
are
greater
than
the
target
MOE.
As
the
mitigation
measure
brings
the
inhalation
MOE
above
1,000
(
which
includes
the
additional
10x
route­
to­
route
extrapolation),
no
confirmatory
inhalation
toxicity
study
is
needed.
Tables
17
and
18
summarize
the
calculation
of
the
MOEs
for
occupational
and
commercial
handlers.

Dermal
and
inhalation
MOEs
for
the
commercial
exposure
scenarios
involving
commercial
pool
operators
pouring
PHMB
liquid
into
multiple
residential
swimming
pools
and
spas
are
greater
than
the
target
MOE
and,
therefore,
are
not
of
concern.
The
commercial
handlers
for
the
medical
premises
did
not
trigger
risks
of
concern
for
the
spray/
mop/
wipe
applications.
The
commercial
uses
are
summarized
in
Table
18.
Page
41
of
48
Table
17.
Short,
Intermediate,
and
Long­
term
Exposures
and
Risks
to
Occupational
Handlers
from
PHMB
Uses
Dermal
Exposurea
(
mg/
lb
ai)
Baseline
Inhalation
Unit
Exposurea
(
mg/
lb
ai)
App.
Rateb
(
lb
ai)
Dermal
c
Dermal
d
Inhalation
c
OCCUPATIONAL
Use
Site
Daily
Daily
Daily
Inhalation
d
Inhalation
Dermal
PRIMARY
USES
Category
Description
Exposure
Dose
Exposure
Daily
Dose
MOE
MOE
e
Application
Method
(
mg/
day)
(
mg/
kg/
day)
(
mg/
day)
(
mg/
kg/
day)

Material
Preservatives
Liquid
pour
Silicons
and
Aqueous
Industrial
Products
0.135
0.00361
1
0.135
0.00193
0.00361
0.0000516
390,000
77,700
0.135
0.00361
10
1.35
0.0193
0.0361
0.000516
39,000
7,770
Leather
Processing
0.135
0.00361
0.6
0.0810
0.00116
0.00217
0.0000310
650,000
129,000
0.135
0.00361
6
0.810
0.0116
0.0217
0.000310
65,000
12,900
Aqueous
Based
Polymer
Latices
0.135
0.00361
1
0.135
0.00193
0.00361
0.0000516
390,000
77,700
0.135
0.00361
10
1.35
0.0193
0.0361
0.000516
39,000
7,770
Animal
Skins
and
Hides
0.135
0.00361
0.52
0.0702
0.00100
0.00188
0.0000268
750,000
150,000
0.135
0.00361
5.20
0.702
0.0100
0.0188
0.000268
75,000
15,000
Cellulosic
Materials
and
Textiles
0.135
0.00361
4
0.54
0.00771
0.0144
0.000206
97,000
19,500
0.135
0.00361
40
5.40
0.0771
0.144
0.00206
9,700
1,950
Aqueous
Mineral
Slurries
0.135
0.00361
1
0.135
0.00193
0.00361
0.0000516
390,000
77,700
0.135
0.00361
10
1.35
0.0193
0.0361
0.000516
39,000
7,770
Aqueous
Based
Adhesives
0.135
0.00361
1
0.135
0.00193
0.00361
0.0000516
390,000
77,700
0.135
0.00361
10
1.35
0.0193
0.0361
0.000516
39,000
7,770
Industrial
Electrocoats
0.135
0.00361
1
0.135
0.00193
0.00361
0.0000516
390,000
77,700
0.135
0.00361
10
1.35
0.0193
0.0361
0.000516
39,000
7,770
Household
Consumer
Products
0.135
0.00361
0.5
0.0675
0.000964
0.00181
0.0000258
750,000
156,000
0.135
0.00361
5
0.675
0.00964
0.0181
0.000258
75,000
15,600
Food
Handling/
Storage
Premises
and
Equipment
Liquid
Pour
Tunnel
Pasteurization
0.135
0.00361
8.34
1.13
0.0161
0.0301
0.000430
47,000
9,320
0.135
0.00361
83.4
11.3
0.161
0.301
0.00430
4,700
932
Industrial
Processes
and
Water
Systems
Liquid
Pour
Oil
Injection
Waters
0.135
0.00361
3.3
0.446
0.00637
0.0119
0.000170
120,000
23,500
Drilling
Muds
0.135
0.00361
1052
142
2.03
3.80
0.0543
370
74
Workover
Fluids
0.135
0.00361
1052
142
2.03
3.80
0.0543
370
74
Liquid
Pump
Drilling
Muds
0.00629
0.000403
1052
6.62
0.0946
0.424
0.00606
3,300
1,590
Workover
Fluids
0.00629
0.000403
1052
6.62
0.0946
0.424
0.00606
3,300
1,590
a
Unit
exposures
based
on
CMA
data
for
inhalation
and
dermal
exposure.
Data
represent
single
layer
clothing
and
no
gloves
b
Application
Rate
based
on
label
information
and
assumptions
on
daily
amounts
handled
c
Dermal/
Inhalation
Exposure
(
mg/
day)=
Unit
Exposure
(
mg/
lb
ai)
*
Application
Rate
(
lb
ai)

d
Dermal/
Inhalation
Dose
(
mg/
kg/
day)=
Dermal
or
Inhalation
Exposure
(
mg/
day)/
Body
Weight
(
70
kg)

e
Dermal
MOE=
Dermal
NOAEL
(
150
mg/
kg/
day)/
Dermal
Dose
(
mg/
kg/
day).
Target
MOE
=
100;
Inhalation
MOE=
Oral
NOAEL
(
20
mg/
kg/
day)/
Inhalation
Dose
(
mg/
kg/
day).
Target
MOE
=
1,000.
Page
42
of
48
Table
18.
Short,
Intermediate,
and
Long­
term
Exposures
and
Risks
to
Residential
and
Commercial
Handlers
from
PHMB
Uses
RESIDENTIAL
HANDLERS/
SECONDARY
OCCUPATIONAL
USES
Dermal
Unit
Exposure
(
mg/
lb
ai)
Baseline
Inhalation
Unit
Exposure
(
mg/
lb
ai)
App.

Rate
(
lb
ai)
Dermal
Daily
Exposure
(
mg/
day)
Dermal
Daily
Dose
(
mg/
kg/
day)
Inhalation
Daily
Exposure
(
mg/
day)
Inhalation
Daily
Dose
(
mg/
kg/
day)
Dermal
MOE
Inhalation
MOE
Use
Site
Application
Method
Category
Description
Liquid
Pour
Swimming
Pools
(
commercial
treater)
0.135
0.00361
22
2.97
0.0424
0.0794
0.00113
3,535
18,000
Liquid
Pour
Swimming
Pools
(
residential)
0.135
0.00361
2.2
0.297
0.00424
0.00794
0.000113
35,000
180,000
Medical
Premises
and
Equipment
Spray
Disinfectant
(
Consumer
Product)
190
1.3
0.012
see
dose
0.033
see
dose
2.2E­
4
4,600
91,000
Mopping
Disinfectant
(
Consumer
Product)
71.6
2.38
0.047
see
dose
0.048
see
dose
0.0016
3,100
13,000
Wiping
Disinfectant
(
Consumer
Product)
2870
67.3
0.012
see
dose
0.492
see
dose
0.012
300
1,700
Residential
and
Public
Access
Spray
Disinfectant
(
Consumer
Product)
220
(
shorts)
1.3
0.006
see
dose
0.019
see
dose
1.1E­
4
8,000
180,000
Mopping
Disinfectant
(
Consumer
Product)
71.6
2.38
0.023
see
dose
0.024
see
dose
0.00078
6,400
26,000
Wiping
Disinfectant
(
Consumer
Product)
2870
67.3
0.006
see
dose
0.25
see
dose
0.0058
610
3,400
Footnotes:

a
Unit
exposures
based
on
PHED
and
CMA
data
for
inhalation
and
dermal
exposure.
Data
represent
single
layer
clothing
and
no
gloves
(
residential
spray
based
on
short­
pants
and
shortsleeved
shirt
 
PHED
and
HED's
Residential
SOPs).

b
Application
Rate
based
on
label
information
and
assumptions
on
daily
amounts
handled.

c
Dermal/
Inhalation
Exposure
(
mg/
day)=
Unit
Exposure
(
mg/
lb
ai)
*
Application
Rate
(
lb
ai).

d
Dermal/
Inhalation
Dose
(
mg/
kg/
day)=
Dermal
or
Inhalation
Exposure
(
mg/
day)/
Body
Weight
(
70
kg).

e
Dermal
MOE=
Dermal
NOAEL
(
150
mg/
kg/
day)/
Dermal
Dose
(
mg/
kg/
day).
Target
MOE
=
100
Inhalation
MOE=
Oral
NOAEL
(
20
mg/
kg/
day)/
Inhalation
Dose
(
mg/
kg/
day).
Target
MOE
=
1,000.

8.0
ENVIRONMENTAL
RISK
ASSESSMENT
Page
43
of
48
8.1
Ecological
Hazard
PHMB
demonstrates
low
toxicity
to
birds
and
mammals
and
high
toxicity
to
freshwater
aquatic
organisms.
All
submitted
ecological
toxicity
studies
were
conducted
with
a
20%
a.
i.
solution
of
PHMB,
which
is
the
technical
formulation,
and
values
were
adjusted
to
100%
a.
i.
to
classify
the
studies
according
to
relative
toxicity.
Submission
of
data
regarding
toxicity
to
marine/
estuarine
organisms,
plants,
or
chronic
effects
was
not
required
for
the
indoor
uses
of
PHMB.
Limited
additional
data
was
found
using
EPA's
ECOTOX
database;
these
data
are
discussed
in
the
Environmental
Risk
chapter
of
this
RED
document.
A
summary
of
submitted
data
is
provided
in
the
table
below.

Table
19.
Summary
of
Submitted
Acute
Ecological
Effects
Toxicity
Data
for
PHMB
Species
LD50/
LC50
NOAEL/
NOAEC
Toxicity
category
(
based
on
100%
AI)

Birds
Northern
bobwhite
(
Colinus
virginianus)
LC50
>
5620
(>
1124
ppm
ai)
NOEC
5620
ppm
(
1124
ppm
ai)
Slightly
toxic
Mallard
duck
(
Anas
platyrhynchos)
LC50
>
5620
(>
1124
ppm
ai)
NOEC
5620
(
1124
ppm
ai)
Slightly
toxic
Mallard
(
Anas
platyrhynchos)
LD50
>
2510
(>
502
mg
ai/
kg)
NOEL
=
2510
(
502
mg
ai/
kg)
Slightly
toxic
Mammals
Laboratory
rat
(
Rattus
norvegicus)
LD50
=
2747
mg/
kg
N/
A
Freshwater
Fish
Rainbow
trout
(
Oncorhynchus
mykiss)
96
hr.
LC50
=
0.02545
ppm
ai
NOEC
=
0.0098
ppm
ai
Very
highly
toxic
Bluegill
sunfish
(
Lepomis
macrochirus)
96
hr.
LC50
=
0.57
(
0.114
ppm
ai);
NOEC
=
0.17
(
0.034
ppm
ai)
Highly
toxic
Freshwater
Invertebrate
Waterflea
(
Daphnia
magna)
48­
hr.
EC50
=
0.18(
0.12
­
0.30)
(
0.036
ppm
ai)
NOEC
=
0.7
(
0.14
ppm
ai)
Highly
toxic
N/
A
=
not
available
NOAEC=
No­
observable
adverse
effect
concentration
Page
44
of
48
8.2
Environmental
Fate
and
Transport
PHMB
is
stable
hydrolytically
in
the
environment
and
has
a
half­
life
of
more
than
thirty
days.
This
may
be
of
environmental
concern
for
surface
water
contamination,
in
the
event
of
exposure
to
surface
water.
Studies
for
other
fate
processes
are
not
required
by
and
have
not
been
submitted
to
the
Agency.

8.3
Environmental
Exposure
and
Risk
Environmental
exposure
modeling
was
not
conducted
for
PHMB.
The
only
use
pattern
likely
to
result
in
significant
outdoor
exposure
is
the
oil
recovery
use;
however,
there
is
a
label
statement
prohibiting
use
over
or
near
marine/
estuarine
(
e.
g.,
offshore)
oil
fields.

The
uses
of
PHMB
considered
in
this
RED
make
it
unlikely
that
any
appreciable
exposure
to
terrestrial
or
aquatic
organisms
would
occur.
Facilities
using
PHMB
for
indoor
industrial
applications
are
required
to
have
NPDES
permits
before
discharging
effluents
into
receiving
waters.

8.4
Endangered
Species
Considerations
The
Agency
has
developed
the
Endangered
Species
Protection
Program
to
identify
pesticides
whose
use
may
cause
adverse
impacts
on
endangered
and
threatened
species
and
to
implement
mitigation
measures
that
address
these
impacts.
The
Endangered
Species
Act
requires
federal
agencies
to
ensure
that
their
actions
are
not
likely
to
jeopardize
listed
species
or
adversely
modify
designated
critical
habitat.
To
analyze
the
potential
of
registered
pesticide
uses
to
affect
any
particular
species,
EPA
puts
basic
toxicity
and
exposure
data
developed
for
risk
assessments
into
context
for
individual
listed
species
and
their
locations
by
evaluating
important
ecological
parameters,
pesticide
use
information,
the
geographic
relationship
between
specific
pesticide
uses
and
species
locations,
and
biological
requirements
and
behavioral
aspects
of
the
particular
species.
A
determination
that
there
is
a
likelihood
of
potential
impact
to
a
listed
species
may
result
in
limitations
on
use
of
the
pesticide,
other
measures
to
mitigate
any
potential
impact,
or
consultations
with
the
Fish
and
Wildlife
Service
and/
or
the
National
Marine
Fisheries
Service
as
necessary.

The
labeled
uses
of
PHMB
are
not
expected
to
result
in
significant
environmental
exposure;
therefore,
adverse
effects
on
endangered
terrestrial
and
aquatic
species
are
not
anticipated.
The
high
toxicity
of
PHMB
to
freshwater
organisms
is
of
concern
in
the
event
of
a
spill
or
misuse
of
the
product.
Product
labeling
indicates
that
the
chemical
is
toxic
to
fish
and
that
discharge
into
water
should
not
occur
except
in
accordance
with
NPDES
requirements.
Page
45
of
48
9.0
INCIDENT
REPORT
ASSESSMENT
The
purpose
of
this
chapter
is
to
review
the
evidence
of
health
effects
in
humans
resulting
from
exposure
to
PHMB.
In
particular,
the
acute
and
chronic
toxicity,
teratogenic/
reproductive
effects,
and
carcinogenicity
are
discussed.

Two
approaches
are
used
in
this
section:

°
The
potential
health
effects
of
PHMB
in
humans,
reported
as
incident
reports
from
different
sources,
are
summarized.

°
A
literature
search
of
chronic
health
effects
associated
with
PHMB
exposure,
including
results
of
epidemiological
studies,
is
summarized.

This
report
summarizes
the
potential
health
effects
of
PHMB
in
humans,
reported
as
incident
reports
from
different
sources.

9.1
Incident
Report
Data
Associated
with
Health
Effects
of
PHMB
Exposure
The
following
databases
have
been
consulted
for
the
poisoning
incident
data
on
the
active
ingredient
PHMB
(
PC
Code:
111801):

a.
OPP
Incident
Data
System
(
IDS)
­
The
Incident
Data
System
of
the
Office
of
Pesticide
Programs
(
OPP)
of
the
Environmental
Protection
Agency
(
EPA)
contains
reports
of
incidents
from
various
sources,
including
registrants,
other
federal
and
state
health
and
environmental
agencies,
and
individual
consumers,
submitted
to
OPP
since
1992.
Reports
submitted
to
the
Incident
Data
System
represent
anecdotal
reports
or
allegations
only,
unless
otherwise
stated.
Typically
no
conclusions
can
be
drawn
implicating
the
pesticide
as
a
cause
of
any
of
the
reported
health
effects.
Nevertheless,
sometimes
with
enough
cases
and/
or
enough
documentation
risk
mitigation
measures
may
be
suggested.

b.
Poison
Control
Centers
­
As
the
result
of
a
data
purchase
by
EPA,
OPP
received
Poison
Control
Center
data
covering
the
years
1993
through
1996
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.

c.
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
Page
46
of
48
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
is
provided.

d.
National
Pesticide
Telecommunications
Network
(
NPTN)
­
NPTN
is
a
toll­
free
information
service
supported
by
OPP.
A
ranking
of
the
top
200
active
ingredients
for
which
telephone
calls
were
received
during
calendar
years
1984­
1991,
inclusive,
has
been
prepared.
The
total
number
of
calls
was
tabulated
for
the
categories
human
incidents,
animal
incidents,
calls
for
information,
and
others.

e.
Published
Incident
Reports
­
Searches
for
incident
reports
associated
with
PHMBrelated
human
health
hazards
published
in
the
scientific
literature
were
conducted.

9.1.1
OPP's
Incident
Data
System
(
IDS)

A
total
of
118
individual
incident
cases
submitted
to
the
EPA
Office
of
Pesticide
Programs
involving
use
of
PHMB­
containing
swimming
pool
products
were
reviewed
to
determine
the
effects
of
exposure
to
PHMB
(
CAS
No.
27083­
27­
8).
All
of
the
incident
reports
reviewed
were
for
residential
use
of
the
products
by
consumers.
In
17
(
i.
e.,
14%)
out
of
the
118
individual
incident
cases
reviewed,
it
was
determined
that
the
exposure
effects
were
the
result
of
not
using
the
product
as
intended
by
the
manufacturer.
They
included
not
following
the
instructions
on
the
label,
accidental
ingestion
of
the
product,
or
splashing
the
concentrated
product
onto
the
skin
or
into
the
eyes.

The
reported
routes
for
exposure
of
the
118
incident
cases
were
dermal
(
58%),
ocular
(
30%),
ingestion
(
9%),
inhalation
(
7%)
and
unknown
(<
1%).
In
some
cases
more
than
one
route
of
exposure
applied
for
an
individual
incident
case
(
e.
g.,
both
dermal
and
ocular
exposure).
The
most
common
symptoms
reported
for
each
exposure
route
are
as
follows:

a.
The
most
common
symptoms
reported
for
cases
of
dermal
exposure
were
skin
irritation/
burning
(
80%),
rash
(
50%),
hives/
welts
(
19%),
itching
(
16%),
skin
discoloration/
redness
(
9%),
allergic
reaction
(
7%),
and
blistering
(
7%).

b.
The
most
common
symptoms
reported
for
cases
of
ocular
exposure
were
eye
irritation/
burning
(
100%),
eye
pain
(
69%),
loss
of
vision
(
17%),
swelling
of
eyes
(
6%),
and
allergic
reactions
(
6%).

c.
The
most
common
symptoms
reported
for
cases
of
exposure
via
ingestion
were
vomiting/
nausea/
abdominal
pain
(
46%),
irritation
to
the
mouth/
throat
(
46%),
respiratory
irritation
including
coughing/
choking
(
18%)
and
diarrhea
(
9%).

d.
The
most
common
symptoms
for
cases
of
exposure
via
inhalation
were
respiratory
irritation
(
75%)
and
coughing/
choking
(
38%).
Page
47
of
48
9.1.2
Poison
Control
Center
All
the
incidences
reported
in
the
Poison
Control
Center
database
were
included
in
the
OPP's
IDS.
No
additional
data
were
reported
in
the
Poison
Control
Center
database
covering
the
years
1993
through
1996.

9.1.3
California
Data
­
1982
through
1996
There
are
no
incidence
reports
submitted
to
the
California
Pesticide
Illness
Surveillance
Program
(
1982­
1996)
database
related
to
PHMB
exposure.

9.1.4
National
Pesticide
Telecommunications
Network
(
NPTN)

There
are
no
incidences
reported
in
the
NPTN
database
related
to
PHMB
exposure.

9.1.5
Incident
Reports
Associated
with
Acute
Toxic
Effects
of
PHMB
Published
in
Scientific
Literature
There
are
no
incident
reports
associated
with
acute
toxic
effects
of
PHMB
published
in
scientific
literature.

9.2
Epidemiologic
Studies
Associated
with
Health
Effects
of
PHMB
in
Humans
No
chronic
health
effects
associated
with
PHMB
exposure
were
reported
in
any
of
the
databases
or
in
epidemiologic
studies.

9.3
Summary
and
Conclusions
There
are
incidences
that
have
been
reported
associated
with
exposure
to
end­
use
products
containing
PHMB.
Dermal
and
ocular
are
the
primary
routes
of
exposure.
Most
of
the
incidences
are
related
to
irritation
and/
or
allergic
type
reaction.
No
chronic
health
effects
associated
with
PHMB
exposure
were
reported
in
any
of
the
databases
or
in
epidemiologic
studies.
Page
48
of
48
10.0
REFERENCES
CMA.
1992.
Chemical
Manufacturers
Association
Antimicrobial
Exposure
Assessment
Study.
Popendorf,
W,
Selim,
M.,
Kross,
B.
The
University
of
Iowa.
MRID
425875­
01.
December
8,
1992.

FDA,
2003a.
"
Guidance
For
Industry:
Preparation
of
Food
Contact
Notifications
and
Food
Additive
Petitions
for
Food
Contact
Substances:
Chemistry
Recommendations.
Final
Guidance."
April,
2003.
http://
www.
cfsan.
fda.
gov/~
dms/
opa2pmnc.
html.
Last
accessed
June
9,
2003.

FDA,
2003b.
"
Sanitizing
Solutions:
Chemistry
Guidelines
for
Food
Additive
Petitions."
January,
1993.
http://
www.
cfsan.
fda.
gov/~
dms/
opa­
cg3a.
html.
Last
accessed
June
9,
2003.

USEPA,
2001.
"
General
Principles
for
Performing
Aggregate
Exposure
and
Risk
Assessments."
US
Environmental
Protection
Agency,
Office
of
Pesticide
Programs.
November
28,
2001.
http://
www.
epa.
gov/
pesticides/
trac/
science/
aggregate.
pdf.
