Document ID: EPA-HQ-OPP-2006-0328-0011
Agency: epa
Document Type: Supporting & Related Material
Title: 
Posted Date: 2006-04-26T04:00Z

March
30,
2006
ShaRon
Carlisle
Antimicrobials
Division,
OPP
U.
S.
Environmental
Protection
Agency
1200
Pennsylvania
Ave.
NW
(
7510C)
Washington,
DC
20460
SUBJECT:
Error
Comments
on
Chlorine
Dioxide
Draft
Risk
Assessment,
Case
4023
In
response
to
the
Draft
Risk
Assessment
for
the
sodium
chlorite/
chlorine
dioxide
RED,
the
Chlorine
Dioxide
Panel
of
the
American
Chemistry
Council
is
submitting
"
corrections"
to
the
errors
we
have
identified
in
the
documents.
In
addition,
we
are
submitting
brief
and
preliminary
science
and
regulatory
policy
comments
that
pertain
to
key
areas
of
the
risk
assessment.
If
possible,
we
would
like
to
meet
with
the
Agency
to
discuss
both
the
errors
and
the
science/
regulatory
policy
issues.

The
Panel
is
comprised
of
major
registrants
of
sodium
chlorite
and
chlorine
dioxide.
These
comments
represent
the
collective
efforts
of
the
Panel
members.

The
detailed
comments
are
presented
in
the
form
of
tracked
changes
and
comments
using
the
current
edition
of
Microsoft
Word.
The
identification
and
comments
of
significance
will
be
summarized
in
this
cover
letter,
with
the
detailed
changes,
comments
and
corrections
noted
in
the
attached
Risk
Assessment
and
the
associated
Science
Chapters.

For
purposes
of
clarity,
we
are
compiling
these
corrections
in
the
order
used
in
the
Draft
Risk
Assessment.

As
part
of
this
submission,
we
are
including
copies
of
additional
reference
materials
and
data
that
were
identified
or
developed
during
our
review.

If
you
have
any
questions
regarding
this
submission,
please
contact
Panel
Manager
for
the
Chlorine
Dioxide
Panel
,
Jon
Busch,
at
703
741­
5633
(
email
address:
jon_
busch@
americanchemistry.
com)

Sincerely,

Jonathon
T.
Busch
Director,
CHEMSTAR
Panels
Manager,
Chlorine
Dioxide
Panel
Error
Comments
on
Chlorine
Dioxide
Draft
Risk
Assessment,
Chlorine
Dioxide
Panel
PHYSICAL/
CHEMICAL
PROPERTIES
CHARACTERIZATION
Detailed
corrections
are
included
in
the
attached
comments
to
the
Product
Chemistry
Chapter.
In
this
chapter,
we
have
expanded
the
scope
to
include
a
brief
discussion
of
the
chemical
characteristics
of
Chlorine
Dioxide
in
aqueous
solutions,
since
ClO2
is
almost
always
produced
and
used
in
(
weak)
aqueous
solutions.

It
is
important
to
note
that
in
solutions
having
a
neutral
or
near
neutral
pH,
chlorine
dioxide
is
relatively
stable
and
exists
as
a
true
undissociated
free
radical.
Significant
hydrolysis
occurs
only
at
pH>
10.

ENVIRONMENTAL
FATE
ASSESSMENT
The
characterization
of
the
generation
of
chlorine
dioxide
in
this
section
is
not
correct.
Conventional
generators
produce
ClO2
either
by
reaction
with
chlorine
or
with
hypochlorite/
acid.
2NaClO2
+
Cl2
 
2ClO2
+
2NaCl
or
2NaClO2
+
NaOCl
+
H2SO4
 
2ClO2
+
NaCl
+
Na2SO4
+
H2O
Although
chlorine
dioxide
does
degrade
in
the
presence
of
sunlight,
most
ClO2
applications
are
in
closed
systems,
and
are
therefore
not
typically
exposed
to
sunlight.

When
used
for
disinfection,
ClO2
typically
degrades
to
chlorite
(
70­
75%),
Chloride
(
10%)
with
some
chlorate
(
15%).
The
actual
ratios
of
these
disinfection
byproducts
will
vary
significantly
between
sites
based
on
many
factors.
It
has
been
generally
accepted
that
the
chlorite
ion
(
not
chlorate)
is
the
primary
disinfection
byproduct
from
the
use
of
ClO2.

It
appears
that
the
Agency
has
consistently
agreed
with
this
position,
but
there
are
frequent
statements
in
the
text
referring
to
chlorate
as
a
decomposition
product
of
ClO2.
We
believe
that
continual
references
to
chlorate
can
lead
to
misinterpretations.

HAZARD
CHARACTERIZATION
The
2­
Generational
reproductive
toxicity
study
(
CMA,
1996)
has
been
assigned
MRID
41715701,
which
has
been
indicated
in
the
mark­
ups
to
the
Risk
Assessment
and
to
the
Toxicity
chapter.
Additionally,
a
version
of
this
study
has
been
published
in
a
peer­
reviewed
journal
as
noted
in
the
mark­
up.

Similarly,
two
other
studies
conducted
by
the
Panel
(
Harrington
et.
al
(
1995a)
and
(
1995b))
were
submitted
and
accepted
as
Guideline
Studies
by
the
Agency.
These
references
have
also
been
noted
in
the
mark­
ups.

EXPOSURE
ASSESSMENT
AND
CHARACTERIZATION
Summary
of
Registered
Uses
In
order
to
put
the
volumes
and
uses
of
chlorine
dioxide
into
a
proper
perspective,
the
Panel
would
like
to
point
out
the
following:
The
Panel
estimates
a
total
of
18,000,000
lbs
of
sodium
chlorite
sold
domestically
(
100%
basis).
All
sodium
chlorite
is
used
to
produce
chlorine
dioxide
The
major
uses
of
ClO2
are
primarily
in
three
use
sites:
 
Municipal
Drinking
Water
(
60%)
 
Cooling
Water
(
30%)
 
Food
Uses
(
8%)
Other
uses
make
up
no
more
than
2%
of
the
total
use
of
this
product.

Dietary
Exposure
and
Risk
We
have
made
a
significant
number
of
corrections
and
comments
which
appear
in
detail
in
the
attached
mark­
up
of
the
Dietary
Risk
Assessment
Chapter.
A
summary
of
some
key
points
include:
 
A
number
of
products
cited
in
this
section
have
already
been
cancelled
voluntarily
and
should
not
be
included
in
the
risk
assessments.
 
The
"
Mushroom
House
Use"
is
covered
by
the
regulation
for
sanitizing
solutions
in
40
CFR180.940(
c),
and
does
not
involve
any
direct
treatment
of
mushrooms.
Instead,
equipment
that
is
used
in
the
processing
of
mushrooms
is
treated
with
a
sanitizing
solution
of
sodium
chlorite/
chlorine
dioxide.
Accordingly,
there
is
no
need
to
establish
any
tolerances
or
tolerance
exemptions
for
this
use.
regulations.
 
The
risks
associated
with
fruit
and
vegetable
washes
appear
to
be
based
on
the
erroneous
assumption
that
sodium
chlorite/
chlorine
dioxide
is
applied
directly
to
RACs.
Instead,
all
of
these
applications
are
covered
by
FDA
regulations
and
must
comply
with
those
regulations.
The
regulation
under
21
CFR
173.300(
b)(
2)
permits
the
use
of
an
antimicrobial
water
rinse
containing
chlorine
dioxide
on
processed
fruits
and
vegetables.
There
are
also
regulations
for
acidified
sodium
chlorite
use
on
fruits
and
vegetables
under
21
CFR
173.325.
All
of
these
regulations
require
that
treated
food
commodity
be
followed
by
a
potable
water
rinse,
or
by
blanching,
cooking,
or
canning.
Residue
data
submitted
to
FDA
showed
no
detectable
chlorite
residues
after
a
water
rinse.
Based
on
this
data
and
the
post­
treatment
requirement,
FDA
concluded,
"
There
will
be
no
exposure
to
chlorite
or
chlorate
from
the
proposed
use
of
the
additive."
In
addition,
an
individual
panel
member
will
be
submitting
their
own
residue
data
confirming
that
no
detectable
chlorite
residue
will
be
present
in
fruits
and
vegetables
washed
with
chlorine
dioxide/
sodium
chlorite.
Dietary
exposures
attributed
to
this
application
should
be
removed.
 
Maximum
use
rates
for
ClO2
as
a
sanitizer
on
food
contact
surfaces
is
limited
to
200
ppm
under
40CFR180.940.
Further,
Sodium
chlorite/
chlorine
dioxide
is
permitted
to
be
used
only
on
food­
processing
equipment
and
utensils
40
CFR
180.940(
c)
and
dairy
processing
equipment
40
CFR
180.940(
b).
The
risk
assessment
for
food
handling
and
eating
establishments
is
present
in
error
and
should
be
deleted.
 
Estimated
exposures
resulting
from
use
of
ClO2
as
a
slimicide
in
pulp/
paper
do
not
take
into
account
the
fact
that
much
of
the
applied
dose
of
ClO2
is
reacted
out
by
the
organics
present
in
the
pulp
slurry,
and
that
even
if
it
were
still
there,
neither
chlorite
nor
ClO2
would
survive
the
paper
drying
process.
At
a
minimum,
the
risk
assessment
should
clarify
that
the
assumed
dietary
exposure
from
the
pulp
and
paper
mill
slimicide
uses
are
highly
conservative
and
overestimate
exposure
by
a
signficicant
amount.
 
Pulp
and
paper
mill
slimicide
uses
are
separate
from
material
preservative
uses.
The
material
preservative
uses
that
EPA
has
included
in
the
dietary
risk
assessment,
i.
e.,
polymer
slurries,
adhesives
and
paper
coatings,
appear
only
one
label
(
EPA
Reg.
No.
74655­
2).
The
registrant
has
advised
the
panel
that
they
are
in
the
process
of
amending
the
label
to
preclude
its
use
in
manufacture
of
food­
contact
packaging
materials.
No
petition
or
other
submission
was
ever
made
to
FDA
and
FDA
has
never
approved
these
uses
for
use
in
food
contact
packaging
or
any
other
food
contact
use.
Therefore,
these
are
not
food
uses
and
the
risk
assessment
for
these
uses
must
be
deleted.

Drinking
Water
Exposures
and
Risks
 
The
EPA
has
requested,
and
the
Panel
is
still
in
the
process
of
obtaining
additional
analytical
data
for
chlorite
for
some
large
utilities.
 
The
assessment
of
drinking
water
exposure
and
risk
indicates
a
concern
for
exposure
to
infants.
The
Panel
believes
that
this
concern
is
actually
mitigated
by
the
fact
that
drinking
water
consumed
by
infants
is
predominantly
as
an
ingredient
in
baby
formulas.
Infant
formulas
contain
vitamins
such
as
ascorbic
acid
(
Vitamin
C)
and
other
reducing
agents
which
are
known
to
react
with
and
remove
chlorine
dioxide
and
chlorite
from
the
product.
See
attached
documentation:
Ozawa
and
Kwan,
(
1987),
and
Simpson
(
2002).

Residential
Exposure/
Risk
Pathway
The
Panel
believes
that
the
Agency
has
significantly
overestimated
the
residential
exposures
for
sodium
chlorite/
chlorine
dioxide.
Registrants
having
residential­
labeled
uses
are
in
the
process
of
establishing
which
products
/
uses
should
be
removed
from
the
residential
market.
Most
products
having
residential
claims
have
not
actually
been
commercially
sold
for
those
uses.
In
addition,
some
products,
although
registered
for
residential
use
are
not
actually
applied
by
the
residents.

OCCUPATIONAL
EXPOSURE
The
Reference
Concentration
(
RfC)
selected
for
chlorine
dioxide
is
inappropriate
as
it
does
not
reflect
the
real­
world
experience
gained
over
decades
of
use.
EPA's
long­
term,
occupational
RfC
of
0.003
ppm
is
two
orders
of
magnitude
lower
than
the
OSHA
PEL
of
0.1
ppm.
As
the
Agency
itself
notes
at
page
37
of
the
Draft
Risk
Assessment,
EPA's
RfCs
are
completely
at
odds
with
those
established
by
OSHA,
ACGIH,
and
NIOSH.
The
Panel
favors
the
acceptance
of
the
existing
OSHA
PEL,
and
is
providing
documentation
to
support
that
position.
(
see
attachment)

INCIDENT
REPORT
ASSESSMENT
As
noted
in
the
Panel
corrections
to
the
Product
Chemistry
Chapter,
chlorine
dioxide
does
not
hydrolyze
except
in
strong
alkaline
solutions.
Further,
there
is
no
known
literature
reference
that
suggests
that
chlorine
dioxide
will
degrade
under
normal
conditions
to
form
chlorine
or
hypochlorite.

The
statements
in
Paragraph
1.5
of
the
Incident
Reports
Chapter
(
and
repeated
on
Pages
10
and
38
of
the
Draft
Risk
Assessment)
regarding
hydrolysis
of
chlorine
dioxide
are
factually
incorrect.
This
error
led
to
the
inclusion
of
many
citations
of
incidents
that
are,
in
fact,
completely
unrelated
to
chlorine
dioxide.
Furthermore,
many
of
the
incidents
cited
involve
exposure
in
swimming
pools.
Chlorine
dioxide
is
not
registered
for
use
in
disinfection
of
swimming
pool
water.

These
significant
errors
and
discrepancies
render
the
Incident
Report
Chapter
to
be
inaccurate
and
irrelevant
to
the
point
where
it
needs
to
be
completely
rewritten.

ECOTOXICOLOGY
ASSESSMENT
Environmental
Modeling/
Exposure
As
AD
is
aware,
all
once­
through
uses
of
sodium
chlorite/
chlorine
dioxide
require
a
National
Pollutant
Discharge
Elimination
System
(
NPDES)
permit.
The
Panel
believes
that
the
site­
specific
NPDES
permit
writer
is
better
able
to
evaluate
the
non­
target
organism
risks
that
may
result
from
the
once­
through
use
of
sodium
chlorite/
chlorine
dioxide
than
does
a
"
macro"
risk
assessment
by
AD.

To
address
the
issue
of
discharges
from
once­
through
systems,
the
Panel
supported
a
study
by
the
University
of
Maryland
to
assess
the
effects
of
chlorite
on
a
wide
variety
of
aquatic
species
[
Fisher
et
al.
2003].
This
data
was
reviewed
by
the
EPA
Office
of
Water.
[
EPA
Letter].
None
of
these
results
have
been
considered
in
this
section.

The
Use
of
the
PDM4
Model.
If
the
aqueous
concentrations
calculated
by
the
PDM4
model
are
used
to
form
a
regulatory
position,
then
it
is
the
inappropriate
model,
for
two
reasons.
First,
OPPT
states
in
its
model
guidance
that
this
tier
I
model
should
not
be
used
for
regulation.
Second,
degradation
of
chlorine
dioxide
and
chlorite
can
be
significant.
The
PDM4
model
does
not
allow
for
degradation.
We
acknowledge
that
mathematical
modeling
would
be
appropriate
for
this
chemical/
use
pattern
combination,
but
PDM4
is
not
the
proper
choice.

Overly
Conservative
Scenarios.
Typical
OPP
regulatory
risk
assessments
attempt
to
calculate
the
upper
90th,
95th,
and
99th
percentiles
for
exposure,
depending
on
the
target
population
and
the
toxicological
endpoint.
The
7Q10
approach
used
in
the
draft
RED
is
more
conservative
than
even
the
upper
99th
percentile,
because
it
is
based
on
the
lowest
seven­
day
flow
in
a
10
year
period,
i.
e.,
the
lowest
seven
days
of
3,644
seven­
day
periods
(
not
Sunday
to
Sunday
weeks).

Dosing
for
Model
Input.
The
use
of
800
ppm
as
the
maximum
dose
for
both
dosing
scenarios
(
intermittent
and
continuous)
is
inappropriate.
This
dose
rate,
appears
only
on
a
single
label
(
EPA
Re.
No.
10707­
32,
issued
to
Baker
Petrolite).
This
product,
a
combination
of
chlorite
and
chlorate,
is
reportedly
obsolete,
and
will
be
cancelled
or
amended
by
the
registrant
to
delete
this
dose.
The
next
higher
dose
rate
(
25
ppm)
appears
on
a
number
of
registered
labels,
however
this
rate
is
still
significantly
higher
than
any
actual
use
rate
for
these
products.
Dose
rates
of
ClO2
at
this
level
would
make
this
product
economically
unacceptable.

As
previously
reported
to
the
Agency,
the
typical
dose
rate
for
once­
through
systems
is
0.25­
3.0
ppm.
The
Panel
believes
that
a
maximum
dose
rate
of
5
ppm
is
more
realistic,
and
is
sufficient
for
achieving
efficacy
in
a
once­
through
system.
The
Panel
therefore
urges
the
Agency
to
not
permit
dose
rates
exceeding
5
ppm.

Ecological
Hazard
and
Risks
The
panel
has
reviewed
the
data
used
by
the
EPA
in
this
chapter
and
notes
the
following
discrepancies
(
See
attached
data
matrix):
 
EPA
endpoints
do
not
agree
with
study
endpoints
in
9
out
of
27
cases.
Some
of
the
differences
are
minor
such
as
incorrect
rounding.
Other
discrepancies
involve
numbers
very
different
from
the
study.
It
is
not
clear
whether
these
are
typos
or
study
reevaluations.
If
the
agency
has
reevaluated
the
studies,
no
explanation
for
the
methods
used
was
provided.
 
The
EPA
lists
NOAEC
levels
when
the
study
does
not
in
8
out
of
27
cases.
In
two
other
cases,
the
study
determined
a
NOAEC
value
and
the
agency
failed
to
list
it.
 
Many
studies
list
EC50
values
for
24,
48,
72
and
96
hours,
yet
the
EPA
has
primarily
chosen
to
rely
on
96
hours,
but
not
consistently.
 
Some
studies
did
not
go
to
96
hours.
In
these
cases,
the
EPA
just
lists
the
values
without
any
explanation.
Therefore,
the
table
comparison
is
similar
to
comparing
apples
to
oranges.
 
In
four
studies,
the
test
material
was
assumed
100%
active
by
the
lab
conducting
the
study.
It
appears
that
an
adjustment
should
be
made.
The
maximum
concentration
of
sodium
chlorite
AI
in
a
registered
product
is
80%,
therefore,
the
actual
test
results
should
be
adjusted
Not
all
of
the
cited
studies
were
immediately
accessible
to
our
reviewers,
however
given
the
number
of
discrepancies
noted
in
the
available
studies,
we
have
some
concerns
ENCLOSURES:
 
Markup
of
Draft
Risk
Assessment
 
Markup
of
Chemistry
Chapter
 
Markup
of
Environmental
Fate
Chapter
 
Markup
of
Toxicology
Chapter
 
Markup
of
Dietary
Risk
Assessment
Chapter
 
Ozawa,
T.,
and
Kwan,
T.
(
1987),
"
Detoxification
of
chlorine
dioxide
(
ClO2)
by
Ascorbic
Acid
in
Aqueous
Solutions:
ESR
Studies,"
Wat.
Res
21
(
2),
229
 
Simpson,
G.
D
(
2002),
US
Patent
6,640,314..
Method
for
Destroying
Chlorite
in
Solution,
 
Panel
Comments
on
OSHA
PEL
vs.
EPA
Occupational
RfD
 
[
Fisher
et
al.
2003]
Fisher,
D.,
Burton,
D.,
Yonkos,
L.,
Turley,
S.,
Ziegler,
G.,
and
Turley,
B.,
"
Derivation
of
Acute
Ecological
Risk
Criteria
for
Chlorite
in
Freshwater
Ecosystems,"
Water
Research,
37(
18),
4359(
Nov
2003).
 
[
EPA
Letter]
re:
Burton
Study
 
Analysis
­
EPA
Chlorine
Dioxide
Environmental
Hazard
and
Risk
Assessment