Document ID: EPA-HQ-OPP-2004-0305-0029
Agency: epa
Document Type: Supporting & Related Material
Title: 
Posted Date: 2006-03-22T05:00Z

PHMB
Dietary
Exposure
Assessments
for
the
Reregistration
Eligibility
Decision
January
18,
2005
Case
3122
PC
Code
111801
A.
Najm
Shamim,
Ph.
D.
Office
of
Pesticide
Programs
Antimicrobials
Division
U.
S.
Environmental
Protection
Agency
1200
Pennsylvania
Avenue,
NW
Washington,
DC
20460
Page
2
of
9
I.
Introduction
Poly(
iminoimidocarbonyliminoimidocarbonyliminohexamethylene)
hydrochloride
(
PHMB)
is
an
antimicrobial
used
in
several
types
of
applications,
including
as
a
fungicide
and
algicide
in
swimming
pools,
as
a
preservative
for
cut
flowers,
and
as
an
all­
purpose
cleaner.
For
the
Reregistration
Eligibility
Decision
(
RED)
process,
the
Agency
has
carried
out
the
dietary
exposure
assessment
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
indirect
food
contact
(
Table
1).
The
four
uses
are
described
below.

Table
1.
Uses
With
Potential
Indirect
Food
Contact
Use
Associated
Product
Registration
Numbers
Disinfectant
on
Countertops
71661­
1
Latex
Adhesives
on
Food
Packaging
72674­
5
Tunnel
Pasteurization
(
EDI
not
calculated)
72674­
5
Disinfectant
Cloths
(
Wipex)
50096­
1
There
are
currently
two
products
registered
that
can
be
used
to
disinfect,
among
other
areas,
countertops
in
kitchens.
One
product
is
a
ready­
to­
use
solution,
(
Reg.#
71661­
1)
while
the
other
is
a
wettable
disposable
cloth
(
Reg#
50096­
1)
that
is
impregnated
with
PHMB.
A
countertop
that
has
been
treated
with
either
of
these
products
may
come
into
contact
with
food
placed
on
the
countertops
and
become
a
source
for
human
ingestion.

There
is
one
product
registered
that
can
be
used
as
a
preservative
in
aqueous
based
adhesives.
This
product
is
a
liquid
concentrate
that
is
added
in
small
quantities
during
the
manufacturing
process.
The
label
specifically
states
that
the
product
"
may
be
used
in
aqueous
based
latex
adhesives
intended
for
food
packaging
applications...."
As
the
adhesive
is
part
of
the
packaging,
it
may
come
into
contact
with
food.

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,
a
possibility
of
infiltration
of
this
product
from
tunnel
pasteurization
water
into
the
food
appears
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
to­
mouth
contact.
Dietary
exposure
due
to
the
tunnel
pasteurization
scenario
to
the
countertop
scenario
indicates
Page
3
of
9
that
the
risk
associated
with
tunnel
pasteurization
will
be
orders
of
magnitudes
lower.
Quantitation
of
exposure
from
tunnel
pasteurization
is
difficult
for
reasons
such
as:

1.
The
concentration
of
PHMB
in
tunnel
pasteurization
waters
is
lower
than
the
concentration
in
other
prodcuts
containing
PHMB
(
maximum
listed
concentration
is
0.1%
for
tunnel
pasteurization
and
0.56%
and
0.158%
for
disinfectant
us).
2.
The
surface
area
of
treated
bottles
or
cans
that
is
transferring
residue
to
an
individual's
hands
should
be
lower
than
the
area
of
a
treated
countertop
that
is
assumed
to
be
transferring
residue
to
an
individual's
food
(
2000
cm2).
3.
The
transfer
of
PHMB
due
to
tunnel
pasteurization
(
bottle
to
hand
to
mouth)
is
less
direct
than
the
transfer
due
to
sanitizing
countertops
(
surface
to
food
to
mouth).

II.
Residue
Information
Review
of
the
Agency's
residue
chemistry
database
does
not
show
any
residues
on
food
or
on
any
raw
agricultural
commodities
(
RACs).
Therefore,
no
residue
chemistry
data
and
analyses
are
included
in
this
dietary
exposure
chapter.

Residue
Chemistry
No
residue
chemistry
data
were
submitted
by
registrants,
nor
were
any
data
asked
for
by
the
Agency,
as
these
uses
do
not
fall
under
the
guidelines
associated
with
residue
chemistry
(
OPPTS
GLN
860.1300,
OPPTS
GLN
860.1340,
OPPTS
GLN
860.1500).
There
are
no
outstanding
residue
chemistry
issues
pertaining
to
this
product.
The
Agency
has
used
available
methods
to
estimate
PHMB
residues
on
food
due
to
migration
of
these
products.
Page
4
of
9
III.
Toxicological
Information
Toxicology
endpoints
for
PHMB
were
selected
by
the
Hazard
Identification
Assessment
Review
Committee
and
are
summarized
in
the
following
table:

Table
2.
Summary
of
Toxicological
Dose
and
Endpoints
for
PHMB
for
Use
in
the
Human
Health
Risk
Assessment
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.
Exposure
Scenario
Dose
Used
in
Risk
Assessment,
UF
Special
FQPA
SF*
and
Level
of
Concern
for
Risk
Assessment
Study
and
Toxicological
Effects
Page
5
of
9
Short­
Term
Incidental
Oral
(
1­
30
days)
NOAEL=
20
mg/
kg/
day
Residential
LOC
for
MOE
=
100
Occupational
=
NA
See
Chronic
RfD
Intermediate­
Term
Incidental
Oral
(
1­
6
months)
NOAEL=
20
mg/
kg/
day
Residential
LOC
for
MOE
=
100
Occupational
=
NA
See
Chronic
RfD
Short­
Term,
Intermediate­
Term,
and
Long­
Term
Dermal
Exposure
Dermal
(
or
oral)
study
NOAEL=
150
mg/
kg/
day
(
Relative
dermal
absorption
rate
=
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
Cancer
Assessment
Review
Committee
has
classified
PHMB
as
showing
"
suggestive
evidence
of
carcinogenicity,
but
not
sufficient
to
assess
human
carcinogenic
potential,"
and
has
concluded
that
quantification
of
human
cancer
risk
is
not
required.

UF
=
uncertainty
factor,
FQPA
SF
=
special
FQPA
safety
factor,
NOAEL
=
no
observed
adverse
effect
level,
LOAEL
=
lowest
observed
adverse
effect
level,
PAD
=
population
adjusted
dose
(
a
=
acute,
c
=
chronic)
RfD
=
reference
dose,
MOE
=
margin
of
exposure,
LOC
=
level
of
concern,
NA
=
not
applicable
NOTE:
The
Special
FQPA
Safety
Factor
recommended
by
the
HIARC
assumes
that
the
exposure
databases
(
dietary
food,
drinking
water,
and
residential)
are
complete
and
that
the
risk
assessment
for
each
potential
exposure
scenario
includes
all
metabolites
and/
or
degradates
of
concern
and
does
not
underestimate
the
potential
risk
for
infants
and
children.

IV.
Calculations
Determining
Estimated
Daily
Intake
(
EDI)
of
a
Pesticide
Used
as
a
Disinfectant
To
calculate
the
EDI
associated
with
use
of
a
PHMB
product
as
a
countertop
disinfectant
(
products
with
Reg.
Nos.
71661­
1
and
50096­
1),
the
Agency
has
used
the
following
equation
for
estimating
the
Estimated
Daily
Intake
of
PHMB
due
to
its
use
as
a
disinfectant.
This
approach
Page
6
of
9
differs
from
the
FDA
approach.

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
EDI
=
Estimated
daily
intake
AR
=
Application
rate
SA
=
Surface
area
of
the
countertops
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
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
PHMB
is
used
as
a
disinfectant
with
a
formulation
concentration
of
0.56%
and
3.17%.
However,
this
last
use
is
as
wettable
Wipex.
For
the
disinfecting
product
as
wettable
Wipex
(
Reg.
No.:
50096­
1),
the
Agency
has
made
the
following
assumption:

A.
According
to
the
label
of
the
product,
the
percent
active
ingredient
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,
an
equal
amount
of
PHMB
is
used
up.
Hence,
each
time
the
Wipex
is
used,
the
percent
of
PHMB
is=
3.17/
20
=
0.158
%.
B.
In
addition,
the
Agency
also
assumed
that
wetting
the
cloth
does
not
change
the
concentration
of
the
active
(
no
dilution
occurs).

2.
EDI
for
PHMB
at
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
Page
7
of
9
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).

FDA
guidelines
assume
that
7
ppb
of
the
product
is
in
diet
from
adhesive
use.
The
Agency
used
this
assumption
in
calculating
the
EDI
as
follows:

1.
If
7
ppb
of
the
product
is
diet,
then
PHMB
(
as
the
a.
i.)
in
the
diet
will
be:
7
ppb
x
0.5%
=
0.035
ppb.
2.
Hence
EDI
=
0.000035
mg/
kg
x
3
kg
in
diet
=
0.000105
mg/
person/
day
=
1.0
x
10­
4
mg/
p/
d.

Other
assumptions
used
include:

1.
As
required
in
the
FDA
rules
for
indirect
food
adhesives,
(
21
CFR
175.105
(
a)
(
2)),
the
adhesive
should
be
separated
from
the
food
by
a
functional
barrier,
used
in
packaging
dry
foods,
or
be
in
contact
with
fatty
and
aqueous
foods
only
in
trace
amounts
at
the
seams
and
at
the
edge
exposure
between
packaging
laminates.
Under
these
assumptions,
the
FDA
guidance
states
that
the
migration
levels
are
generally
assumed
to
be
no
greater
than
50
ppb.
2.
The
FDA
default
consumption
factor
for
adhesives
is
0.14.
3.
The
FDA
recommended
total
food
intake
is
3000
g/
person/
day.
4.
The
FDA
default
assumption
for
the
amount
of
packaging
required
for
food
is
0.1
in2
of
paper
per
gram
of
food.
5.
As
a
conservative
assumption,
it
is
assumed
that
latex
adhesive
represents
10%
of
the
packaging.
Also,
it
is
assumed
that
paper
weighs
50
mg/
in2.

Data
used
in
the
calculation
are
presented
in
Table
3.
Based
on
these
assumptions,
the
estimated
daily
intake
is
5.25x10­
8
mg/
person/
day.
Page
8
of
9
Table
3.
Calculations
of
EDI
for
Use
of
PHMB
in
Latex
Adhesives
Parameter
Value
Rationale
Food
Intake
3000
g/
person
FDA
default
assumption
Amount
of
Packaging
0.1
in2/
g
food
FDA
default
assumption
Weight
of
Paper
50
mg/
in2
FDA
default
assumption
Percent
of
Packaging
That
Is
Latex
10%
EPA
assumption
Percent
Latex
Ingested
7x10­
7%
FDA
default
assumption
(
50
ppb
x
0.14)

Percent
Active
Ingredient
0.5%
Maximum
concentration
listed
on
product
label
(
Reg.
No.
72674­
5)

Calculated
Results
Estimated
Daily
Intake
5.25
x
10­
8
mg/
person/
day
EDI
=
(
Food
Intake)
*
(
Packaging
Amt)
*
(
Paper
Wt)
*
(%
Latex
Packaging)
/
100
*
(%
Latex
Ingested)
/
100
*
(%
a.
i.)
/
100
V.
Results/
Discussion
Total
dietary
intake
and
risk
was
solely
based
on
the
disinfectant
solution
use
of
PHMB.
An
assumption
was
made
that
an
individual
would
not
be
using
both
the
disinfectant
solution
and
Wipex
cloth
at
the
same
time
to
clean
the
food
contact
surfaces
in
one's
home.
Since
the
disinfectant
solution
represents
the
worst
case,
exposure
to
it
was
used
to
represent
the
disinfectant
use
in
the
dietary
assessment.
The
latex
adhesive
use
was
considered
to
be
a
negligible
level
of
exposure
and
would
not
contribute
significantly
to
dietary
risk.
Page
9
of
9
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