Document ID: EPA-HQ-OPP-2006-0328-0002
Agency: epa
Document Type: Supporting & Related Material
Title: 
Posted Date: 2006-04-26T04:00Z

Page
1
of
49
Chlorine
Dioxide
Draft
Risk
Assessment
Case
4023
Antimicrobials
Division
Office
of
Pesticide
Programs
U.
S.
Environmental
Protection
Agency
200
Pennsylvania
Avenue,
NW
Washington,
DC
20460
April
6,
2006
Page
2
of
49
TABLE
OF
CONTENTS
EXECUTIVE
SUMMARY............................................................................................
3
1.0
PHYSICAL/
CHEMICAL
PROPERTIES
CHARACTERIZATION
..............................
12
1.1
Chemical
Identification.............................................................................................
12
1.2
Physical/
Chemical
Properties
........................................................................................
12
2.0
ENVIRONMENTAL
FATE
ASSESSMENT................................................................
13
3.0
HAZARD
CHARACTERIZATION..............................................................................
13
3.1
Hazard
Profile...............................................................................................................
13
3.2
FQPA
Considerations
...................................................................................................
17
3.3
Dose­
Response
Assessment
..........................................................................................
18
3.4
Endocrine
Disruption                             ...
19
4.0
EXPOSURE
ASSESSMENT
AND
CHARACTERIZATION.......................................
20
4.1
Summary
of
Registered
Uses
........................................................................................
20
4.2
Dietary
Exposure
and
Risk............................................................................................
20
4.3
Drinking
Water
Exposures
and
Risks
............................................................................
23
4.4
Residential
Exposure/
Risk
Pathway
..............................................................................
24
4.4.1
Residential
Handler
Scenarios
..............................................................................
24
4.4.2
Residential
Post
Application
Exposure..................................................................
26
5.0
AGGREGATE
RISK
ASSESSMENTS
AND
RISK
CHARACTERIZATIONS............
28
5.1
Acute
and
Chronic
Aggregate
Risks
..............................................................................
29
5.2
Short­
and
Intermediate­
Term
Aggregate
Exposures
and
Risks......................................
29
6.0
CUMULATIVE
RISK..................................................................................................
31
7.0
OCCUPATIONAL
EXPOSURE...................................................................................
32
7.1
Occupational
Handler
...................................................................................................
32
7.2
Occupational
Post
Application
Exposure.......................................................................
34
8.0
INCIDENT
REPORT
ASSESSMENT..........................................................................
37
9.0
ECOTOXICOLOGY
ASSESSMENT...........................................................................
38
10.0
REFERENCES                                .
44
Page
3
of
49
EXECUTIVE
SUMMARY
Chlorine
dioxide
and
sodium
chlorite
are
active
ingredients
in
numerous
products
used
in
the
control
of
bacteria,
fungi,
and
algal
slimes.
In
addition,
chlorine
dioxide
and
sodium
chlorite
are
used
as
material
preservatives
and
as
disinfectants.
At
this
time,
products
containing
chlorine
dioxide
and
sodium
chlorite
are
intended
for
agricultural,
commercial,
industrial,
medical
and
residential
use.
The
agricultural
premises
and
equipment
uses
include
the
disinfection
of
hard
surfaces
and
equipment
(
such
as
hatching
facilities
and
mushroom
houses)
and
water
systems
(
such
as
chiller
water
and
humidification
water
in
poultry
houses).
Commercial,
industrial,
and
medical
uses
include
disinfection
of
ventilation
systems,
hard
surfaces
(
e.
g.,
floors,
walls,
and
laboratory
equipment),
water
systems,
pulp/
paper
mills,
and
food
rinses.
Residential
uses
include
disinfection
of
hard
surfaces
(
e.
g.,
floors,
bathrooms),
heating
ventilating
and
airconditioning
(
HVAC)
systems,
and
pool
&
spa
water
circulation
system
treatments.
In
addition,
there
is
a
continuous
release
gas
product
(
sachet)
for
the
home
to
control
odors.

Environmental
Fate:
Chlorine
dioxide
and
sodium
chlorite
are
assessed
together
because
chlorine
dioxide
is
produced
by
a
reaction
of
sodium
chlorite
(
and
sometimes
sodium
chlorate)
with
hypochlorite
/
acid.
In
addition,
chlorite
is
a
breakdown
product
of
chlorine
dioxide.
A
major
route
of
exposure
is
through
drinking
water.

Chlorine
dioxide
has
a
short
half
life
and
in
the
presence
of
sunlight
and
will
break
down
into
chloride
and
chlorate
ions,
and
ultimately,
oxygen
is
formed.
Sodium
chlorite
dissolves
in
water,
breaking
down
into
chloride
and
chlorate
ions
under
similar
conditions
as
chlorine
dioxide.
Chlorate
and
chlorite
ions
tend
to
only
undergo
biodegradation
under
anaerobic
conditions
degrading
to
chloride
and
oxygen.
Biodegradation
of
chlorate
and
chlorite
have
been
observed
in
anoxic
groundwater,
sediments
and
some
soils.
No
adsorption/
desorption
constants
(
Kds)
have
been
measured
or
reported
in
published
literature
for
either
chlorite
or
chlorate.
These
ions
are
likely
to
be
mobile
and
may
travel
from
surface
to
groundwater
easily.
The
estimated
log
Kow
of
chlorine
dioxide
is
­
3.22
and
for
sodium
chlorite
is
­
7.17.
It
is
not
expected
that
either
would
bioaccumulate
in
aquatic
organisms.

Hazard:
The
acute
toxicity
of
chlorine
dioxide
(
79%
a.
i.)
is
moderate
by
the
oral
route
(
LD50
=
292
mg/
kg
[
males];
340
mg/
kg
[
females];
Toxicity
Category
II).
The
acute
toxicity
of
chlorine
dioxide
using
sodium
chlorite
as
the
test
material
(
80%
a.
i.)
is
considered
minimal
by
the
dermal
route
(
LD50
>
2000
mg/
kg;
Toxicity
Category
III).
By
the
inhalation
route,
using
sodium
chlorite
as
the
test
material
(
80.6%),
chlorine
dioxide
was
moderately
toxic
(
LC50
=
0.29
mg/
L,
Toxicity
Category
II).
For
primary
eye
irritation,
chlorine
dioxide
(
2%
a.
i.)
was
a
mild
irritant
(
Toxicity
Category
III),
but
the
technical
test
material
was
not
used.
For
primary
dermal
irritation,
sodium
chlorite
(
80%
a.
i.)
was
a
primary
irritant
(
Toxicity
Category
II).
For
dermal
sensitization,
there
are
no
acceptable
animal
studies
for
chlorine
dioxide
or
sodium
chlorite.

The
subchronic
toxicity
database
is
considered
adequate
for
characterizing
the
Page
4
of
49
subchronic
oral
and
inhalation
toxicity
of
chlorine
dioxide/
chlorite.
Daniel
et
al.
(
1990)
exposed
groups
of
10
male
and
10
female
Sprague­
Dawley
rats
to
chlorine
dioxide
in
drinking
water
for
90
days
at
concentrations
of
0,
25,
50,
100,
or
200
mg/
L
(
0,
2,
4,
6,
or
12
mg/
kg­
day
chlorine
dioxide
for
males
and
0,
2,
5,
8,
or
15
mg/
kg­
day
chlorine
dioxide
for
females).
The
LOAEL
for
this
study
is
25
mg/
L
(
2
mg/
kg­
day)
based
on
a
significant
increase
in
incidence
of
nasal
lesions.
In
a
study
by
Harrington
et
al.
(
1995),
rats
(
15/
sex/
group)
were
administered
doses
of
0,
10,
25,
or
80
mg/
kg­
day
sodium
chlorite
(
equivalent
to
0,
7.4,
19,
or
60
mg
chlorite/
kg­
day,
respectively)
via
gavage
for
13
weeks.
The
NOAEL
for
this
study
is
7.4
mg/
kg­
day,
and
the
LOAEL
is
19
mg/
kg­
day,
based
on
stomach
lesions
and
increases
in
spleen
and
adrenal
weights.
Dalhamn
(
1957)
and
Paulet
and
Desbrousses
(
1970,
1972,
and
1974)
are
co­
critical
inhalation
toxicity
studies
included
in
the
subchronic
toxicity
database
for
chlorine
dioxide/
chlorite.
A
NOAEL
of
0.1
ppm
(~
0.28
mg/
m3)
was
selected
from
Dalhamn
(
1957)
and
a
LOAEL
of
1.0
ppm
(~
2.8
mg/
m3)
was
selected
from
Paulet
and
Desbrousses
(
1970,
1972,
and
1974),
based
on
respiratory
distress
and
decreased
body
weights
observed
in
exposed
animals.

In
a
developmental
toxicity
study
(
Orme
et
al.,
1985),
a
NOAEL
of
20
mg/
L
(
3
mg/
kg/
day)
was
established
based
on
neurodevelopmental
effects
in
the
offspring
of
rats
exposed
to
chlorine
dioxide
in
drinking
water.
A
developmental
toxicity
study
(
MRID
41715701)
conducted
in
rabbits
using
sodium
chlorite
(
purity
80.58%)
showed
a
dose­
related
increase
in
incidence
of
does
with
reduced
fecal
output
during
the
dosing
period,
days
7
to
19,
which
was
considered
consistent
with
decreased
food
consumption;
the
NOAEL
for
developmental
and
maternal
toxicity
was
200
ppm
(
12­
14
mg/
kg/
day).
A
two­
generational
reproductive
toxicity
study
(
CMA,
1996,
MRID
4535890)
was
conducted
with
sufficient
numbers
of
animals
of
both
sexes
and
examined
numerous
endpoints.
The
NOAEL
for
this
study
is
35
ppm
(
2.9
mg/
kg­
day
chlorite)
and
the
LOAEL
is
70
ppm
(
5.7
mg/
kg­
day
chlorite)
based
on
lowered
auditory
startle
amplitude
and
altered
liver
weights
in
two
generations.

One
chronic
toxicity
study
(
Haag,
1949)
is
included
in
the
toxicity
database
for
chlorine
dioxide.
The
study
was
determined
to
be
of
limited
use
in
the
assessment
of
chronic
toxicity
because
an
insufficient
number
of
animals
were
tested
per
group
and
pathology
was
conducted
on
only
a
small
number
of
animals.
In
addition,
the
study
did
not
provide
adequate
evaluations
of
more
sensitive
parameters,
which
would
have
been
more
useful
in
the
overall
assessment
of
chronic
toxicity.

Chlorine
dioxide
has
not
been
formally
assessed
for
carcinogenic
potential.
The
available
dermal
carcinogenicity
studies
do
not
definitively
characterize
the
carcinogenicity
of
chlorine
dioxide,
and
additional
studies
may
be
required.
One
subchronic
study
(
Daniel
et
al.,
1990)
examined
the
effects
of
administration
of
chlorine
dioxide
to
groups
of
male
and
female
Sprague­
Dawley
rats
(
10/
sex/
dose)
at
dose
levels
of
0,
25,
50,
100,
or
200
mg/
L
for
90
days
in
drinking
water.
A
significant
increase
in
the
incidence
of
nasal
lesions
(
goblet
cell
hyperplasia
and
inflammation
of
nasal
turbinates)
was
found
at
all
dose
levels
tested.
The
significance
of
these
findings
is
uncertain
as
they
have
not
been
observed
in
other
long­
term
studies
of
chlorine
dioxide.

Data
on
the
mutagenicity
of
chlorine
dioxide
exist
in
the
open
scientific
literature
as
well
Page
5
of
49
as
within
the
Agency's
database
of
submitted
studies.
In
Miller
et
al.
(
1986)
negative
effects
were
reported
in
Salmonella
strains
TA98
and
TA100
from
a
400­
fold
drinking
water
concentrate
of
chlorine
dioxide,
whereas
a
4000­
fold
concentrate
was
mutagenic
to
strain
TA98
only
in
the
absence
of
metabolic
activation.
In
Accession
No.
265867,
chlorine
dioxide
was
positive
for
forward
mutations
under
non­
activated
conditions
(
dose­
related
from
3.2­
24.3
µ
g/
ml)
and
activated
conditions
(
48.3
µ
g/
mL)
in
L5178Y/
TK
cells,
positive
for
structural
chromosome
aberrations
under
non­
activated
and
activated
conditions
(
10,
15,
and
50
µ
g/
ml),
and
negative
for
increased
transformed
foci
up
to
cytotoxic
levels.
In
vivo
micronucleus
and
bone
marrow
chromosomal
aberration
assays
in
Swiss
CD­
1
mice
administered
0.1 
0.4
mg
chlorine
dioxide
via
gavage
for
5
consecutive
days
were
negative,
as
was
a
sperm­
head
abnormality
assay
in
B6C3F1
mice
administered
0.1 
0.4
mg
via
gavage
for
5
consecutive
days
(
0,
3.2,
8,
and
16
mg/
kg­
day)
(
Meier
et
al.,
1985).

Neurotoxicity
of
chlorine
dioxide
has
been
observed.
In
the
two­
generation
reproduction
toxicity
study
(
CMA,
1996),
significant
changes
were
observed
in
maximum
response
in
startle
amplitude
and
absolute
brain
weight
in
F1
rat
pups
at
a
dose
of
3
mg/
kg/
day.
In
the
Orme
et
al.
(
1985)
developmental
toxicity
study,
neurobehavioral
deficits
consisting
of
decreased
exploratory
and
locomotor
activities
were
observed
in
offspring
at
a
maternal
dose
of
14
mg/
kg/
day.

Toxicity
Endpoints:
The
toxicity
endpoints
used
in
this
document
to
assess
potential
risks
include
acute
and
chronic
dietary
reference
doses,
and
short­,
intermediate­
and/
or
longterm
incidental
oral,
dermal,
and
inhalation
doses.

Dietary/
Oral
Endpoints:
The
chronic
NOAEL
is
3
mg/
kg/
day.
This
endpoint
is
based
on
a
two­
generation
reproduction
toxicity
study
(
CMA,
1996)
and
a
developmental
toxicity
study
in
rats
(
Orme
et
al.,
1985).
An
uncertainty
factor
of
100
(
10x
for
interspecies
extrapolation
and
10x
for
intraspecies
variability)
was
applied.
An
acute
dietary
endpoint
was
not
identified
in
the
data
base
for
chlorine
dioxide.

Dermal
Endpoints:
The
short­,
intermediate­,
and
chronic­
term
dermal
endpoint
is
3
mg/
kg/
day
and
is
based
on
a
two­
generation
reproduction
toxicity
study
and
a
developmental
toxicity
study
in
rats
(
CMA,
1996;
Orme
et
al.,
1985).
The
target
MOE
is
100
for
residential
and
occupational
exposure.

Inhalation
Endpoints:
The
inhalation
route
of
exposure
to
chlorine
dioxide
is
assessed
for
three
distinct
subpopulations:
(
1)
occupational
exposures
(
8
hours/
day,
5
days/
week),
(
2)
onetime
exposures
for
residential
uses
(
e.
g.,
HVAC
systems,
mopping
floors,
etc),
and
(
3)
long­
term
exposure
for
continuous
release
products
in
the
home
(
24
hours/
day,
7
days/
week).
Several
animal
studies
were
used
to
develop
reference
concentrations
(
RfCs).
The
effects
seen
at
various
concentrations
include
rhinorrhea,
altered
respiration,
respiratory
infection,
bronchial
inflammation,
alveolar
congestion
and
hemorrhage,
vascular
congestion,
and
peribronchiolar
edema.
Readers
are
referred
to
USEPA
(
2000a)
for
a
detailed
review
of
the
effects
seen
at
specific
concentrations
and
exposure
durations
along
with
the
derivation
of
the
RfC.
In
summary,
the
occupational
RfC
is
determined
to
be
0.003
ppm
and
represents
an
8­
hour
time
weighted
average
(
TWA).
The
one­
time
residential
exposure
scenario
is
represented
by
the
RfC
Page
6
of
49
of
0.05
ppm
and
the
RfC
for
long­
term,
continuous
exposure
is
0.00007
ppm.
The
RfC
methodology
incorporates
the
uncertainty
factors
into
the
concentration.
For
inhalation,
the
RfC
is
compared
directly
to
the
air
concentration
of
interest.
Inhalation
risks
are
of
concern
if
the
air
concentrations
people
are
exposed
to
exceed
the
RfC.

FQPA
Safety
Factor:
When
the
original
toxicity
endpoint
assessment
was
conducted,
the
Hazard
Identification
Assessment
Review
Committee
(
HIARC)
concluded
that
an
extra
10x
uncertainty
factor
under
the
Food
Quality
Protection
Act
should
be
considered
in
risk
assessments
conducted
for
chlorine
dioxide.
This
recommendation
was
based
upon
evidence
of
susceptibility
in
a
two­
generation
reproduction
toxicity
study
in
rats
and
evidence
of
susceptibility
from
scientific
literature
reports.

Since
that
time,
the
Health
Effects
Division
of
the
Office
of
Pesticide
Programs
issued
policy
guidance
September
of
2001
regarding
the
determination
of
the
appropriate
FQPA
safety
factor
in
tolerance
assessment.
This
guidance
states
that
whereas
in
the
past
"...
OPP
has
routinely
applied
an
additional
FQPA
safety
factor
where
data
on
a
pesticide
shows
increased
susceptibility
or
sensitivity
(
either
qualitative
or
quantitative)
in
the
developing
organism,"
It
is
the
intent
that
"...
OPP
will
now
put
greater
emphasis
on
analyzing
the
degree
of
concern
and,
rather
than
apply
an
additional
safety
factor
based
solely
on
the
identification
of
heightened
sensitivity
or
susceptibility,
will
conduct
a
case­
by­
case
weight
of
evidence
approach
that
qualitatively
examines
the
level
of
concern
for
sensitivity
/
susceptibility
and
assess
whether
traditional
uncertainty
factors
already
incorporated
into
the
risk
assessment
are
adequate
to
protect
the
safety
of
infants
and
children.
Using
this
approach,
in
many
cases
the
concerns
regarding
pre­
and
postnatal
toxicity
can
be
addressed
when
a
Reference
Dose
(
RfD)
or
Margin
of
Exposure
(
MOE)
is
based
on
the
pre­
or
postnatal
endpoints
in
the
offspring."

The
endpoint
selected
for
both
dietary
and
non­
dietary
exposures
to
chlorine
dioxide
was
based
upon
adverse
effects
observed
in
offspring
from
developmental
and
reproductive
toxicity
data.
Consistent
with
the
approach
used
by
the
EPA's
Office
of
Water
for
use
of
chlorine
dioxide
as
a
drinking
water
disinfectant
and
the
updated
guidance
on
selection
of
a
safety
factor
under
FQPA,
the
endpoint
selected
for
assessment
of
risk
from
dietary
and
non­
dietary
exposure
to
chlorine
dioxide
was
felt
to
be
protective
of
potentially
susceptible
populations
including
children,
based
upon
the
selection
of
an
endpoint
and
effects
observed
in
offspring
and
the
use
of
an
NOAEL
value
based
on
those
effects.
Therefore,
it
was
concluded
that
an
additional
safety
factor
under
FQPA
was
not
necessary.

Dietary
Exposure:
The
Agency
has
conducted
a
dietary
exposure
and
risk
assessment
for
use
of
chlorine
dioxide
in
products
used
in
the
control
of
bacteria,
fungi,
and
algal
slimes;
as
well
as
its
use
as
a
material
preservative
and
disinfectant
all
of
which
may
end
in
indirect
food
contact
scenarios.
For
chronic
dietary
exposure,
the
risk
from
indirect
food
contact
is
highest
for
children
(
61%
of
the
chronic
PAD).
For
an
adult,
the
chronic
dietary
exposure
is
16%
of
the
chronic
PAD.

For
direct
food
contact,
AD
conducted
a
chronic
risk
assessment
for
the
fruit
and
vegetable
washes
which
were
applied
post­
harvest.
The
chronic
risks
appear
to
be
below
the
levels
of
concern
(
7.5%
of
cPAD
for
adults
and
42%
of
the
cPAD
for
children
between
the
ages
Page
7
of
49
of
1
and
2
years
of
age).

Total
dietary
risks
(
from
direct
and
indirect
food
contact)
are
slightly
above
the
Agency's
level
of
concern
for
children
(
103%
of
the
cPAD).
However,
the
chronic
risks
appear
to
be
below
the
level
of
concern
for
adults
(
23%
of
the
cPAD).

Water
Exposure
and
Risk:
Chlorine
dioxide
and
sodium
chlorite
are
used
as
disinfectants
in
many
water
treatment
plants.
Office
of
water
conducted
an
eighteen
month
monitoring
study
for
the
determination
of
maximum
contaminant
levels
(
MCL)
and
maximum
contaminant
level
goals
(
MCLG)
of
chlorite
in
the
drinking
water
that
reached
consumers.
AD
used
the
results
from
this
study
and
determined
for
all
infants
less
than
one
year
of
age,
the
cPAD
(
145%)
exceeds
the
level
of
concern.

Residential
Exposure
and
Risk:
Residential
uses
of
chlorine
dioxide
and/
or
sodium
chlorite
products
that
are
applied
by
homeowners
include
the
control
of
mold
and
mildew.
For
the
exposure
assessment,
household
cleaning
products
were
grouped
together
to
be
represented
by
a
higher
application
rate
from
a
sodium
chlorite
product.
The
post
application
scenario
is
based
on
a
product
that
applies
chlorine
dioxide
to
floors
that
have
the
potential
for
children
playing.
Three
scenarios
(
mopping,
spraying,
and
placing
tablets
into
pools/
spas)
were
examined
for
residential
uses
in
the
risk
assessment.
The
scenarios
were
evaluated
based
on
the
Residential
Exposure
Assessment
Standard
Operating
Procedures
(
SOPs),
product
label
maximum
application
rates,
related
use
information,
Agency
standard
assumptions,
Pesticide
Handlers
Exposure
Database
(
PHED)
unit
exposure
data,
and
Chemical
Manufacturing
Association
(
CMA)
unit
exposure
data.
The
calculated
dermal
MOE
is
less
than
the
target
MOE
of
100
for
only
the
application
of
tablets
to
pool
water
circulation
systems.
The
dermal
MOE
for
applications
to
pool
water
systems
is
46.
This
risk
can
be
mitigated
with
the
use
of
gloves
(
MOE=
500).

Residential
post
application
exposures
result
when
bystanders
(
adults
and
children)
come
in
contact
with
chlorine
dioxide
in
areas
where
pesticide­
treated
end­
use
products
have
recently
been
applied
(
e.
g.,
treated
hard
surfaces/
floors),
or
when
children
incidentally
ingest
the
pesticide
residues
through
mouthing
the
treated
end
products/
treated
articles
(
i.
e.,
hand­
tomouth
or
object­
to­
mouth
contact).
For
the
purposes
of
this
screening­
level
assessment,
four
post
application
scenarios
have
been
considered:
(
1)
exposure
to
residue
from
hard
floors
that
have
been
cleaned/
mopped
with
a
generic
cleaner
containing
chlorine
dioxide,
(
2)
exposure
to
chlorine
dioxide
used
by
commercial
applicators
to
clean
residential
HVAC
systems,
(
3)
exposure
to
a
continuous
release
(
gas)
deodorizer,
and
(
4)
pool
&
spa
treatments.

The
child
short­
and
intermediate­
term
dermal
MOE
for
contact
following
hard
surface
disinfection
is
above
the
target
MOE
of
100
for
residential
and
daycare
settings
(
MOE
=
280).
The
short­
and
intermediate­
term
incidental
oral
MOE
following
hard
surface
disinfection
are
above
the
target
MOE
of
100
for
residential
and
daycare
settings
(
MOE
=
2,300),
and
thus
are
not
of
concern.

Inhalation
exposures
due
to
post
application
activities
could
occur
for
children
and
adults
after
the
treatment
of
floors;
adults
and
children
after
the
treatment
of
HVAC
systems;
and
adults
Page
8
of
49
and
children
during
the
use
of
continuous
release
(
gas)
deodorizers.
Chlorine
dioxide
and/
or
sodium
chlorite
can
be
applied
as
an
aqueous
solution
to
hard
surfaces
such
as
floors
and
as
a
dust
to
carpets.
For
the
floor
treatments,
a
theoretical
approach
to
estimating
chlorine
dioxide
air
concentrations
indicates
an
8­
hour
time
weighted
average
(
TWA
)
air
concentration
of
0.02
ppm
after
a
1­
hour
restricted
entry
interval
(
REI).
If
one
could
assume
that
residents
would
stay
out
of
the
house
for
the
first
hour,
the
8­
hour
TWA
is
0.02
ppm
which
is
below
the
RfC
of
0.05
ppm.

For
HVAC
treatments,
monitoring
data
are
available.
The
air
concentrations
monitored
indicated
the
highest
peak
concentration
of
0.02
ppm
and
the
average
of
the
peak
concentrations
was
below
the
detection
limit
of
0.01
ppm.
The
short­
term
inhalation
RfC
for
chlorine
dioxide
is
0.05
ppm.
Therefore,
inhalation
exposures
from
HVAC
treatments
are
not
expected
to
be
a
concern.

For
the
continuous
release
deodorizers,
a
bounding
estimate
of
air
concentration
is
presented
based
on
the
application
rate
and
the
label­
referenced
longevity
of
the
pouches/
sachets.
The
theoretical
constant
air
concentration
would
be
0.52
ppm
assuming
no
air
exchange
and
no
build
up
of
chlorine
dioxide
over
time
because
of
the
short
half
life.
The
RfC
for
long­
term
continuous
exposure
is
0.00007
ppm.
Therefore,
the
theoretical
concentration
from
the
product's
release
is
of
concern.

Aggregate
Exposure
and
Risk:
In
order
for
a
pesticide
registration
to
continue,
it
must
be
shown
that
the
use
does
not
result
in
"
unreasonable
adverse
effects
on
the
environment".
Aggregate
exposure
is
the
total
exposure
to
a
single
chemical
(
or
its
residues)
that
may
occur
from
dietary
(
i.
e.,
food
and
drinking
water),
residential,
and
other
non­
occupational
sources,
and
from
all
known
or
plausible
exposure
routes
(
oral,
dermal,
and
inhalation).
Aggregate
risk
assessment
were
conducted
for
acute
(
1
day),
short­
term
(
1­
30
days),
intermediate­
term
(
1­
6
months)
and
chronic
(
several
months
to
lifetime)
exposures.

The
acute
and
chronic
aggregate
risk
assessments
are
based
on
dietary
and
drinking
water
exposures.
For
chlorine
dioxide
acute
dietary
risks
were
not
assessed
based
on
the
lack
of
acute
endpoints.
Dietary
exposures
from
indirect
food
uses
(
e.
g.,
use
in
food­
contact
packaging)
and
from
direct
food
uses
were
aggregated
together
along
with
the
drinking
water
exposures
for
a
total
dietary
exposure.
The
chronic
aggregate
risk
estimates
associated
with
chlorine
dioxide
from
dietary
uses
are
below
the
Agency's
level
of
concern
for
adults
at
67%
of
the
cPAD.
However
the
dietary
risks
are
above
the
level
of
concern
for
children
(
165%
of
the
cPAD).

The
short­
and
intermediate­
term
aggregate
assessments
were
conducted
for
adults
and
children.
The
following
representative
scenarios
were
included
in
the
aggregate
assessments:
Short­
term,
Adults:
°
dietary,
chronic
direct
and
indirect
°
handling
cleaning
products
via
spray
(
dermal
only)
°
handling
cleaning
products
via
mopping
(
dermal
only)
°
drinking
water,
chronic
Short­
and
intermediate
term,
Children:
°
dietary,
chronic
direct
and
indirect
Page
9
of
49
°
post
application
exposure
to
cleaning
product
residues
(
dermal
and
oral)
°
drinking
water,
chronic
Since
the
toxicity
endpoints
for
the
oral
and
dermal
routes
of
exposure
are
based
on
the
same
study
and
same
toxic
effect,
these
two
routes
are
aggregated
together.
The
inhalation
route
is
based
on
a
different
effect
and
therefore
that
route
is
not
included
in
the
aggregate.
For
the
aggregate
of
the
inhalation
route,
only
the
continuous
release
product
may
co­
occur
with
the
other
uses
and
the
inhalation
risk
for
the
continuous
release
is
of
concern
by
itself.
The
aggregate
risks
(
oral
+
dermal)
are
not
of
concern
for
adults,
as
the
total
aggregate
MOE
is
130,
which
is
above
the
target
of
100.
For
children,
the
aggregate
risk
estimates
are
again
below
the
target
MOE
of
100
(
MOE=
44)
and
thus
are
of
concern.
It
should
be
noted
that
several
conservative
assumptions
were
used
in
this
assessment.

Occupational
Exposure
and
Risk:
Potential
occupational
handler
exposure
from
the
use
of
chlorine
dioxide
products
can
occur
in
various
use
sites,
including
agricultural
premises,
food
handling,
commercial
and
institutional
premises,
medical
premises,
human
drinking
water
systems,
industrial
processes
and
water
systems,
application
to
material
preservatives,
and
swimming
pools
and
other
aquatic
areas.

For
the
occupational
handler
dermal
risk
assessment,
the
short­
and
intermediate­
term
risks
calculated
at
baseline
exposure
(
no
gloves
and
no
respirators)
were
above
target
MOEs
for
all
scenarios
(
i.
e.,
dermal
MOEs
were
>
100),
except
for
the
following:

Agricultural
premises
and
equipment:

$
application
to
hard
surfaces:
low
pressure
handwand
(
MOE=
31),

$
application
to
hard
surfaces:
mopping
(
MOE=
70),
and
$
application
to
hard
surfaces:
foam
applicator
equipment
(
MOE=
8).

Food
Handling,
Commercial/
Institutional,
and
Medical
Premises
and
Equipment:

$
application
to
hard
surfaces:
mopping
(
MOE=
66
for
commercial
and
3
for
medical
facilities).

There
is
the
potential
for
the
off
gassing
of
chlorine
dioxide
during
some
applications
that
are
not
totally
enclosed
(
e.
g.,
spray
aqueous
solution,
mopping,
pouring,
etc).
Although
no
occupational
air
monitoring
data
have
been
submitted
to
assess
the
inhalation
route,
EPA
has
obtained
air
concentration
measurements
from
OSHA.
OSHA
maintains
a
data
base
known
as
the
Integrated
Management
Information
System
(
IMIS).
The
IMIS
entries
for
chlorine
dioxide
are
available
for
7
industry
Standard
Industrial
Classification
(
SIC)
codes.
The
summary
results
of
the
33
observations
taken
from
8­
hour
TWA
personal
air
samplers
for
chlorine
dioxide
indicate
that
21
of
those
measurements
were
below
the
LOD
of
0.004
ppm.
In
addition,
of
the
33
TWA
measurements,
only
3
were
at
or
above
0.1
ppm.
It
is
also
important
to
note
that
the
OSHA
PEL
for
chlorine
dioxide
is
0.1
ppm.
Facilities
using
chlorine
dioxide
are
not
required
to
mitigate
inhalation
exposures
until
the
air
concentration
reaches
0.1
ppm.
Based
on
the
occupational
inhalation
toxicological
endpoint
selected
for
chlorine
dioxide
(
i.
e.,
RfC
of
0.003
ppm),
levels
at
or
near
the
PEL
are
of
concern.
In
fact,
the
capability
(
i.
e.,
LOD)
of
the
OSHA
sampling
method
is
insufficient
for
the
occupational
RfC
presented
in
this
document.
Page
10
of
49
Reconciliation
of
the
EPA
risk­
based
RfC
and
the
current
OSHA
standards
will
be
made
during
the
regulatory
decision
phase
of
the
Reregistration
Eligibility
Decision
(
RED)
for
chlorine
dioxide.
Incident
Reports:
There
are
some
reported
incidents
associated
with
exposure
to
enduse
products
containing
chlorine
dioxide.
Inhalation
is
the
primary
route
of
exposure.
Most
of
the
incidents
are
related
to
irritation
reaction.
In
aqueous
media,
chlorine
and
chlorine
dioxide
dissolve
and
hydrolyze
to
produce
hypochlorous
acid
and
hypochlorite
ion,
which
react
in
swimming
pools
to
produce
breakdown
products
such
as
chloramines,
haloacetic
acid,
haloacetonitriles,
haloketones,
chloropicrin,
and
chloral
hydrate.
This
process
makes
it
difficult
to
separate
out
incidents
with
chlorine
dioxide
from
incidents
associated
with
chlorine,
chlorite
and
hypochlorite
ions.

The
most
common
symptoms
reported
for
cases
of
inhalation
exposure
were
respiratory
irritation/
burning,
irritation
to
mouth/
throat/
nose,
coughing/
choking,
shortness
of
breath,
dizziness,
flu­
like
symptoms,
and
headache.
Exposure
to
chlorinated
pool
water
has
also
been
reported
to
cause
red,
watery
eyes
as
well
as
dermal
effects,
such
as
generalized
rashes.

Ecological
Hazard
and
Risk:
For
terrestrial
animals,
the
results
of
studies
to
examine
the
toxicity
of
chlorine
dioxide/
sodium
chlorite
to
birds
indicate
these
chemicals
range
from
slightly
to
highly
toxic
to
birds
on
an
acute
oral
basis
and
from
slightly
toxic
to
practically
nontoxic
on
a
subacute
dietary
basis.
For
freshwater
aquatic
animals,
the
results
of
studies
examining
the
toxicity
of
chlorine
dioxide/
sodium
chlorite
to
freshwater
fish
indicate
these
chemicals
range
from
slightly
toxic
to
practically
non­
toxic
on
an
acute
basis.
For
aquatic
invertebrates,
the
studies
indicate
that
chlorine
dioxide
and
sodium
chlorite
range
from
very
highly
toxic
for
technical
grade
sodium
chlorite
a.
i.
to
practically
non­
toxic
for
the
formulated
product
on
an
acute
basis.
Results
of
toxicity
studies
indicate
that
chlorine
dioxide/
sodium
chlorite
are
slightly
toxic
to
estuarine/
marine
fish
on
an
acute
basis
and
range
from
highly
toxic
to
slightly
toxic
to
estuarine/
marine
invertebrates
on
an
acute
basis.

For
terrestrial
plants,
results
of
toxicity
studies
indicate
that
chlorine
dioxide/
sodium
chlorite
are
moderately
toxic
to
terrestrial
plants.
However,
since
the
maximum
label
rate
for
many
of
the
chlorine
dioxide/
sodium
chlorite
once­
through
cooling
labels
was
not
used
in
these
tests,
it
is
necessary
to
conduct
Tier
II
testing
with
rice.
For
aquatic
plants,
toxicity
study
results
indicate
chlorine
dioxide/
sodium
chlorite
are
moderately
toxic
to
aquatic
plants.
The
oncethrough
cooling
tower
use
of
chlorine
dioxide/
sodium
chlorite
requires
that
5
aquatic
plant
tests
be
conducted
due
to
the
algaecidal
nature
of
the
chemical
and
the
likelihood
of
exposure
to
aquatic
plants
in
surface
waters
receiving
industrial
facility
outfall
from
the
cooling
system;
however,
only
one
study
(
1
species)
under
this
topic
has
been
submitted
and
5
are
required.
The
following
aquatic
plant
studies
are
still
required:
blue­
green
cyanobacteria
(
Anabaena
flosaquae
freshwater
diatom
(
Navicula
pelliculosa),
marine
diatom
(
Skeletonema
costatum)
and
floating
macrophyte
(
Lemna
gibba).

For
aquatic
organisms,
acute
risk
is
anticipated
from
the
use
of
chlorine
dioxide/
sodium
chlorite
in
once­
through
cooling
towers
based
on
the
modeling
conducted.
At
the
highest
doses,
there
is
risk
to
freshwater
and
marine/
estuarine
fish
and
invertebrates
and
aquatic
plants,
and
at
the
lowest
doses
there
is
risk
only
to
freshwater
invertebrates.
Chronic
risk
to
aquatic
organisms
Page
11
of
49
cannot
be
assessed
at
this
time
due
to
the
lack
of
chronic
toxicity
endpoints
for
fish
and
aquatic
invertebrates.
When
the
required
aquatic
chronic
toxicity
testing
described
above
is
submitted,
chronic
risk
to
these
organisms
will
be
assessed.
Listed
Species:
Acute
risk
to
listed
birds
and
mammals
is
not
anticipated
from
the
use
of
chlorine
dioxide
and
sodium
chlorite
products
due
to
low
exposure
and
low
toxicity.
Further
discussion
is
needed
before
it
can
be
determined
if
there
are
risks
to
listed
aquatic
organisms
from
the
once
through
cooling
tower
use
of
chlorine
dioxide/
sodium
chlorite.
Chronic
risks
to
listed
aquatic
organisms
cannot
be
assessed
at
this
time;
this
risk
will
be
assessed
when
required
chronic
toxicity
data
are
submitted
to
and
evaluated
by
the
Agency.
Page
12
of
49
1.0
PHYSICAL/
CHEMICAL
PROPERTIES
CHARACTERIZATION
1.1
Chemical
Identification
Chemical
identification
parameters,
including
CAS
Number
and
molecular
formula
are
provided
in
Table
1.

Table
1.
Chemical
Identification
Information
for
Chlorine
Dioxide
and
Sodium
Chlorite
Property
Chlorine
Dioxide
Sodium
Chlorite
OPP
Chemical
Code
020503
020502
CAS
Number
10049­
04­
4
7758­
19­
2
Molecular
Formula
ClO2
NaClO2
1.2
Physical/
Chemical
Properties
The
physical
and
chemical
properties
of
chlorine
dioxide
and
sodium
chlorite
are
shown
in
Table
2.

Table
2.
Physical/
Chemical
Properties
of
Chlorine
Dioxide
and
Sodium
Chlorite
Property
Chlorine
Dioxide
Sodium
Chlorite
Molecular
Weight
67.45
g/
mol
90.45
g/
mol
Color
Yellow
to
Reddish
Yellow
White
Melting
Point
­
59oC
180­
200oC
(
decomposes)

Boiling
Point
11oC
n/
a
Odor
Strongly
pungent,
chlorine­
like
n/
a
Physical
State
Gas
at
room
temperature
Solid
Density
1.64
g/
ml
at
0oC
(
liquid)
1.614
g/
ml
at
10o
C
(
liquid)
2.468
g/
ml
(
as
a
solid)

Vapor
Pressure
490
mm
Hg
(
0oC)
>
760
mm
Hg
(
25oC)
n/
a
Stability
Dilute
solutions
are
stable
if
kept
cool
and
in
the
dark.
Unstable
when
exposed
to
sunlight
n/
a
Solubility
(
water)
3.01
g/
L
at
25oC
and
34.5
mmHg
390
g/
L
at
30oC
Page
13
of
49
2.0
ENVIRONMENTAL
FATE
ASSESSMENT
A
detailed
environmental
fate
assessment
for
chlorine
dioxide
and
sodium
chlorite
is
presented
in
the
attached
appendix.

Chlorine
dioxide
and
sodium
chlorite
are
assessed
together
because
chlorine
dioxide
is
produced
by
a
reaction
of
sodium
chlorite
(
and
sometime
sodium
chlorate)
and
hypochlorite/
acid.
In
addition,
chlorite
is
a
breakdown
product
of
chlorine
dioxide.
Major
antimicrobial
uses
of
chlorine
dioxide
and/
or
sodium
chlorite
are
as
water
disinfectants
and
pulp/
paper
industry
disinfectants.
The
major
route
of
exposure,
therefore,
is
through
drinking
water.

Chlorine
dioxide
has
a
short
half
life
and
in
the
presence
of
sunlight
and
will
break
down
into
chloride
and
chlorate
ions
(
between
pH
4
and
7).
At
pH
lower
than
4,
its
breakdown
products
are
chlorite
and
chlorate.
Chlorite
is
the
dominant
breakdown
product.
Ultimately,
oxygen
is
formed.
Sodium
chlorite
dissolves
in
water,
breaking
down
into
chloride
and
chlorate
ions
under
similar
conditions
as
chlorine
dioxide.
Chemical
degradation
of
sodium
chlorite
commonly
occurs
in
water
as
well
as
in
the
presence
of
suspended
soil
particles
containing
ions,
like
Fe(
II),
Mn(
II),
I­,
and
S­
2,
through
redox
reactions.
The
final
breakdown
products
are
chloride
and
oxygen.
These
same
end
products
are
obtained
when
sodium
chlorite
is
heated.

Chlorate
and
chlorite
ions
tend
to
only
undergo
biodegradation
only
under
anaerobic
conditions.
Biodegradation
of
chlorate
and
chlorite
have
been
observed
in
anoxic
groundwater,
sediments
and
some
soils.
The
end
products
are
the
same
as
stated
above:
chloride
and
oxygen.
No
adsorption/
desorption
constants
(
Kds)
have
been
measured
or
reported
in
published
literature
for
either
chlorite
or
chlorate.
These
ions
are
likely
to
be
mobile
and
may
travel
from
surface
to
groundwater
easily.
The
estimated
log
Kow
of
chlorine
dioxide
is
­
3.22
and
for
sodium
chlorite
is
­
7.17.
It
is
not
expected
that
either
would
bioaccumulate
in
aquatic
organisms.

3.0
HAZARD
CHARACTERIZATION
3.1
Hazard
Profile
A
detailed
hazard
assessment
for
chlorine
dioxide
is
presented
in
the
attached
appendix.

Acute
Toxicity.
The
acute
toxicity
of
chlorine
dioxide
(
79%
a.
i.)
is
considered
moderate
by
the
oral
route
(
Toxicity
Category
II)
and
minimal
by
the
dermal
route
using
sodium
chlorite
as
the
test
material
(
80%
a.
i.)
(
Toxicity
Category
III).
By
the
inhalation
route,
chlorine
dioxide
was
moderately
toxic
(
Toxicity
Category
II)
using
sodium
chlorite
as
the
test
material
(
80.6%).
For
primary
eye
irritation,
chlorine
dioxide
(
2%
a.
i.)
was
a
mild
irritant
(
Toxicity
Category
III),
but
the
technical
test
material
was
not
used.
For
primary
dermal
irritation,
sodium
chlorite
(
80%
a.
i.)
was
a
primary
irritant
(
Toxicity
Category
II).
There
are
no
acceptable
animal
studies
for
chlorine
dioxide
or
sodium
chlorite
for
dermal
sensitization.
Table
3
presents
the
acute
toxicity
data
for
chlorine
dioxide/
sodium
chlorite
and
Table
4
highlights
the
key
toxicological
studies
for
chlorine
dioxide.
Page
14
of
49
Subchronic
Toxicity.

Chlorine
dioxide:
A
subchronic
oral
toxicity
study
(
Daniel
et
al.,
1990)
conducted
in
the
rat
showed
systemic
effects
after
repeated
oral
administration
of
chlorine
dioxide
in
the
drinking
water
at
doses
of
0,
25,
50,
100
or
200mg/
L.
A
significant
decrease
in
body
weights
and
body
weight
gain
was
evident
(
26­
29%
lower
than
controls)
in
males
at
the
200
mg/
L
treatment
level.
Significant
reductions
were
also
observed
in
water
(
in
the
 
50
mg/
L
treatment
for
males
and
 
25
mg/
L
treatment
for
females)
and
food
consumption
(
in
the
200
mg/
L
treatment
for
males).
Both
absolute
liver
(
for
males;
 
50
mg/
L)
and
spleen
weights
(
for
females;
 
25
mg/
L)
decreased.
In
males
exposed
to
100
or
200
mg/
L,
serum
lactate
dehydrogenase
and
aspartate
aminotransferase
levels
decreased
and
serum
creatinine
levels
increased.
A
significant
increase
in
incidence
of
nasal
lesions
(
goblet
cell
hyperplasia
and
inflammation
of
nasal
turbinates)
was
found
in
males
( 
25
mg/
L)
and
females
( 
100
mg/
L).

Subchronic
inhalation
toxicity
studies
(
Dalhamn,
1957;
Paulet
and
Desbrousses,
1970,
1972,
and
1974)
conducted
in
the
rat
have
resulted
in
pulmonary
edema
and
nasal
bleeding
(
at
levels
of
260
ppm
during
a
single
2­
hour
exposure)
as
well
as
respiratory
distress
and
bronchopneumonia
(
in
rats
exposed
to
3­
minute
exposure
of
decreasing
concentrations
of
chlorine
dioxide
from
3,400
ppm
to
800
ppm
once
a
week
for
3
consecutive
weeks).
At
levels
of
10
ppm
(
4
hours/
day
for
9
days
in
a
13­
day
period),
rats
exhibited
rhinorrhea,
altered
respiration,
and
respiratory
infection.

Sodium
chlorite:
A
subchronic
oral
toxicity
study
(
Harrington
et
al.,
1995)
conducted
in
the
rat
showed
systemic
effects
after
repeated
oral
(
gavage)
administration
of
sodium
chlorite
at
doses
of
0,
10,
25
or
80
mg/
L
(
corresponding
to
0,
7.4,
19
or
60
mg/
kg/
day).
Four
animals
died
in
the
60
mg/
kg/
day
treatment
level
and
both
males
and
females
exhibited
salivation,
significantly
decreased
erythrocyte
counts,
and
decreased
total
serum
protein
levels.
In
the
60
mg/
kg/
day
treatment
level,
males
exhibited
significantly
decreased
hematocrit
and
hemoglobin
levels
and
increased
methemoglobin
and
neutrophil
levels,
while
females
exhibited
significantly
decreased
methemoglobin
levels.
In
the
60
mg/
kg/
day
treatment
level,
the
following
observations
were
also
noted:
morphological
changes
in
erythrocytes
in
some
animals
of
both
sexes,
significant
increases
in
relative
adrenal
and
spleen
weights
in
the
males,
increases
in
absolute
and
relative
spleen
and
adrenal
weight
in
females,
and
increases
in
relative
liver
and
kidney
weights
in
the
females.
The
60
mg/
kg/
day
treatment
level
also
exhibited
histopathologic
alterations
such
as
squamous
epithelial
hyperplasia,
hyperkeratosis,
ulceration,
chronic
inflammation,
and
edema
in
the
stomachs
of
seven
males
and
eight
females.
In
the
19
mg/
kg/
day
treatment
level,
alterations
such
as
occasional
salivation
in
two
males,
hematologic
alterations
in
males
(
increased
methemoglobin
levels
and
neutrophil
count,
decreased
lymphocyte
count),
increases
in
absolute
and
relative
spleen
and
adrenal
weights
in
females,
and
histologic
alterations
in
the
stomach
of
two
males,
similar
to
those
seen
in
the
high­
dose
group,
were
reported.

Developmental
Toxicity.
Page
15
of
49
Chlorine
dioxide:
A
developmental
toxicity
study
(
Orme
et
al.,
1985)
was
conducted
in
rats
with
chlorine
dioxide
administered
in
the
drinking
water
at
doses
of
0,
1,
20
or
100
mg/
L.
A
depression
of
serum
thyroxin
(
T4)
and
an
increase
of
serum
triiodothyronine
(
T3)
were
observed
in
pups
at
weaning
at
the
100
mg/
L
(
14
mg/
kg/
day)
dose
level,
as
well
as
a
decrease
in
neurobehavioral
exploratory
and
locomotor
activities.
These
effects,
however,
were
not
observed
in
pups
at
the
20
mg/
L
dose
level
(
3
mg/
kg).
Pups
administered
chlorine
dioxide
by
gavage
at
14
mg/
kg/
day
on
post­
natal
days
5­
20
showed
a
larger
depression
of
serum
T4
levels
and
greater
delays
in
development
of
exploratory
and
locomotor
behavior
activity.

Sodium
chlorite:
A
developmental
toxicity
study
(
MRID
41715701)
was
conducted
in
rabbits
using
sodium
chlorite
(
purity
80.58%)
administered
in
the
drinking
water
at
doses
of
0,
200,
600
or
1200
ppm).
Mean
intake
of
the
test
compound
via
the
drinking
water
was
suppressed
in
a
dose­
related
fashion
at
the
highest
levels,
especially
over
the
first
few
days
of
dosing.
The
sole
treatment­
related
clinical
effect
was
a
dose­
related
increase
in
incidence
of
does
with
reduced
fecal
output
during
the
dosing
period,
days
7
to
19,
which
was
considered
consistent
with
decreased
food
consumption.
Among
gross
findings
in
scheduled
sacrifices
were:
pitted
kidneys
in
two
mid­
dose
and
one
high­
dose
animal;
alopecia
in
two
low­
dose,
three
middose
and
two
high­
dose
does;
and
thoracic
fluid
in
one
low­
dose
animal.

Reproductive
Toxicity.
A
two­
generation
reproduction
study
(
CMA,
1996)
was
conducted
in
which
sodium
chlorite
was
administered
to
rats
(
F0
generation)
in
their
drinking
water
at
concentrations
of
0,
35,
70
or
300
ppm.
The
F1
generation
was
given
the
same
treatment
as
their
parents.
Because
of
a
reduced
number
of
litters
in
the
70
ppm
F1­
F2a
generation,
the
F1
animals
were
re­
mated
to
produce
a
F2b
generation.
All
generations,
primarily
in
the
70
and
300
ppm
treatment
groups,
exhibited
decreases
in
water
and
food
consumption,
and
body
weight
gain.
In
the
300
ppm
treatment
group,
there
were
significant
reductions
in
absolute
and
relative
liver
weight
in
the
F0
females
and
F1
males
and
females,
reduced
pup
survival,
reduced
body
weight
at
birth
and
throughout
lactation
in
F1
and
F2
rats,
lower
thymus
and
spleen
weight
in
both
generations,
lowered
incidence
of
pups
exhibiting
normal
righting
reflex
and
with
eyes
open
on
postnatal
day
15,
alteration
in
clinical
condition
in
F2
animals
chosen
for
neurotoxicity,
decrease
in
absolute
brain
weight
for
F1
males
and
F2
females,
delay
in
sexual
development
in
males
(
preputial
separation)
and
females
(
vaginal
opening)
in
F1
and
F2
rats,
and
lower
red
blood
cell
parameters
in
F1
rats.
Reduced
absolute
and
relative
liver
weights
were
also
observed
in
the
70
ppm
treatment
groups
for
F0
females
and
F1
males.

Chronic
Toxicity.
A
chronic
toxicity
study
(
Haag,
1949)
was
conducted
with
a
group
of
rats
exposed
to
0,
1,
2,
4,
8,
100,
or
1,000
mg/
L
chlorite
in
the
drinking
water
(
0,
0.09,
0.18,
0.35,
0.7,
9.3,
or
81
mg/
kg­
day)
for
2
years.
Animals
exposed
to
chlorite
concentrations
of
100
or
1,000
mg/
L
exhibited
treatment­
related
renal
pathology.
These
effects
were
also
observed
in
a
group
of
animals
administered
sodium
chloride
at
a
concentration
equimolar
to
1,000
mg
sodium
chlorite/
L.
The
study
was
limited
because
an
insufficient
number
of
animals
were
tested
per
group,
pathology
was
conducted
on
a
small
number
of
animals,
and
it
did
not
provide
adequate
evaluations
of
more
sensitive
parameters,
which
would
have
been
more
useful
in
the
overall
assessment
of
chronic
toxicity.

Carcinogenicity.
Robinson
et
al.
(
1986)
assessed
the
potential
for
chlorine
dioxide
to
induce
proliferative
epidermal
hyperplasia
in
dorsally
shaved
female
SENCAR
mice
exposed
to
Page
16
of
49
0,
1,
10,
100,
300,
or
1,000
ppm
liquid
chlorine
dioxide.
The
data
from
this
study
are
considered
inadequate
for
characterizing
the
carcinogenicity
of
chlorine
dioxide/
chlorite.
A
dermal
carcinogenicity
study
(
Kurokawa
et
al.,
1984)
evaluated
the
ability
of
chlorite
to
act
as
a
complete
carcinogen.
In
this
study,
groups
of
20
female
SENCAR
mice
were
exposed
twice
weekly
for
51
weeks
to
20
mg/
mL
sodium
chlorite
in
acetone.
The
study
was
also
considered
inadequate
because
the
exposure
was
for
less
than
a
lifetime,
a
high
incidence
of
Sendai
virus
was
found
in
the
rats,
and
mortality
was
high
in
the
mouse
control
group
because
of
excessive
fighting.

Mutagenicity.
Several
studies
exist
on
the
mutagenicity
of
chlorine
dioxide
both
in
the
open
literature
and
in
the
Agency's
database
of
submitted
studies.
In
one
study
(
Miller
et
al.,
1986),
negative
effects
in
Salmonella
strains
TA98
and
TA100
from
a
400­
fold
drinking
water
concentrate
of
chlorine
dioxide
and
positive
effects
in
a
4000­
fold
concentrate
to
strain
TA98
only
in
the
absence
of
metabolic
activation
were
reported.
Another
study
indicated
chlorine
dioxide
was
positive
for
forward
mutations
under
non­
activated
and
activation
conditions
in
L5178Y/
TK
cells
(
Accession
no.
265867).
Chlorine
dioxide
was
positive
for
structural
chromosome
aberrations
under
non­
activated
and
activated
conditions
(
Accession
no.
265867)
and
was
negative
for
increased
transformed
foci
up
to
cytotoxic
levels
(
Accession
no.
265867).
In
vivo
micronucleus
and
bone
marrow
chromosomal
aberration
assays
in
Swiss
CD­
1
mice
administered
0.1 
0.4
mg
chlorine
dioxide
via
gavage
for
5
consecutive
days
were
negative,
as
was
a
sperm­
head
abnormality
assay
in
B6C3F1
mice
administered
0.1 
0.4
mg
via
gavage
for
5
consecutive
days
(
0,
3.2,
8,
and
16
mg/
kg­
day)
(
Meier
et
al.,
1985).

Metabolism.
Oral
studies
have
provided
information
regarding
the
pharmacokinetics
of
both
chlorine
dioxide
and
chlorite.
Chlorine
dioxide
rapidly
dissociates,
predominantly
into
chlorite
(
which
itself
is
highly
reactive)
and
chloride
ion
(
Cl­),
ultimately
the
major
metabolite
of
both
chlorine
dioxide
and
chlorite
in
biological
systems
(
Abdel­
Rahman
et
al.,
1984).
Urine
is
the
primary
route
of
elimination,
predominantly
in
the
form
of
chloride
ion
(
Abdel­
Rahman
et
al.,
1984).
Chlorite
(
ClO2
­)
does
not
persist
in
the
atmosphere
either
in
ionic
form
or
as
chlorite
salt.
The
rapid
appearance
of
36Cl
in
plasma
following
oral
administration
of
chlorine
dioxide
(
36ClO2)
or
chlorite
(
36ClO2
­)
has
been
shown
in
laboratory
animals
(
Abdel­
Rahman
et
al.,
1984).
In
rats,
absorbed
36Cl
(
from
36ClO2
or
36ClO2
sources)
is
slowly
cleared
from
the
blood
and
is
widely
distributed
throughout
the
body
(
Abdel­
Rahman
et
al.,
1984).

Neurotoxicity.
In
a
two­
generation
reproduction
toxicity
study
(
CMA,
1996)
conducted
with
sodium
chlorite
(
81.4%
purity)
administered
in
the
drinking
water,
significant
changes
were
observed
in
maximum
response
in
startle
amplitude
and
absolute
brain
weight
in
F1
rat
pups
at
a
dose
of
3
mg/
kg/
day.
In
another
developmental
toxicity
study
(
Orme
et
al.,
1985),
neurobehavioral
deficits
in
offspring
were
observed
at
a
maternal
dose
of
14
mg/
kg/
day.
Page
17
of
49
Table
3.
Acute
Toxicity
Profile
for
Chlorine
Dioxide/
Sodium
chlorite
Guideline
Number
Study
Typea
/
Test
substance
(%
a.
i.)
MRID
Number/
Citation
Results
Toxicity
Category
870.1100
Acute
oral
(
79%
chlorine
dioxide)
43558601
LD50
=
292
mg/
kg
(
males)
LD50
=
340
mg/
kg
(
females)
II
870.1200
Acute
dermal
(
80%
sodium
chlorite)
40168704
LD50
>
2000
mg/
kg
III
870.1300
Acute
inhalation
(
80.6%
sodium
chlorite)
42484101
LC50
=
0.29
mg/
L
II
870.2400
Primary
eye
irritation
(
2%
chlorine
dioxide)
43441903
Mild
irritant
III
870.2500
Primary
dermal
irritation
(
80%
sodium
chlorite)
40168704
Primary
irritant
II
870.2600
Dermal
sensitization
No
acceptable
sensitization
study
available.

a
The
available
acute
studies
are
all
graded
as
acceptable.
An
acceptable
dermal
sensitization
study
is
not
available
in
the
database.

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."

When
the
original
toxicity
endpoint
assessment
was
conducted,
the
Hazard
Identification
Assessment
Review
Committee
(
HIARC)
concluded
that
an
extra
10x
uncertainty
factor
under
the
Food
Quality
Protection
Act
should
be
considered
in
risk
assessments
conducted
for
chlorine
dioxide.
This
recommendation
was
based
upon
evidence
of
susceptibility
in
a
two­
generation
reproduction
toxicity
study
in
rats
and
evidence
of
susceptibility
from
scientific
literature
reports.

Since
that
time,
the
Health
Effects
Division
of
the
Office
of
Pesticide
Programs
issued
policy
guidance
September
of
2001
regarding
the
determination
of
the
appropriate
FQPA
safety
factor
in
tolerance
assessment.
This
guidance
states
that
whereas
in
the
past
"...
OPP
has
routinely
applied
an
additional
FQPA
safety
factor
where
data
on
a
pesticide
shows
increased
Page
18
of
49
susceptibility
or
sensitivity
(
either
qualitative
or
quantitative)
in
the
developing
organism,"
It
is
the
intent
that
"...
OPP
will
now
put
greater
emphasis
on
analyzing
the
degree
of
concern
and,
rather
than
apply
an
additional
safety
factor
based
solely
on
the
identification
of
heightened
sensitivity
or
susceptibility,
will
conduct
a
case­
by­
case
weight
of
evidence
approach
that
qualitatively
examines
the
level
of
concern
for
sensitivity
/
susceptibility
and
assess
whether
traditional
uncertainty
factors
already
incorporated
into
the
risk
assessment
are
adequate
to
protect
the
safety
of
infants
and
children.
Using
this
approach,
in
many
cases
the
concerns
regarding
pre­
and
postnatal
toxicity
can
be
addressed
when
a
Reference
Dose
(
RfD)
or
Margin
of
Exposure
(
MOE)
is
based
on
the
pre­
or
postnatal
endpoints
in
the
offspring."

The
endpoint
selected
for
both
dietary
and
non­
dietary
exposures
to
chlorine
dioxide
was
based
upon
adverse
effects
observed
in
offspring
from
developmental
and
reproductive
toxicity
data.
Consistent
with
the
approach
used
by
the
EPA's
Office
of
Water
for
use
of
chlorine
dioxide
as
a
drinking
water
disinfectant
and
the
updated
guidance
on
selection
of
a
safety
factor
under
FQPA,
the
endpoint
selected
for
assessment
of
risk
from
dietary
and
non­
dietary
exposure
to
chlorine
dioxide
was
felt
to
be
protective
of
potentially
susceptible
populations
including
children,
based
upon
the
selection
of
an
endpoint
and
effects
observed
in
offspring
and
the
use
of
an
NOAEL
value
based
on
those
effects.
Therefore,
it
was
concluded
that
an
additional
safety
factor
under
FQPA
was
not
necessary.

3.3
Dose­
Response
Assessment
The
doses
and
toxicological
endpoints
selected
by
ADTC
for
various
exposure
scenarios
are
summarized
in
Table
4
below.

Table
4.
Summary
of
Toxicological
Doses
and
Endpoint
Selection
for
Chlorine
dioxide/
Sodium
chlorite
Exposure
Scenario
Dose
Used
in
Risk
Assessment
(
mg/
kg/
day)
UF/
MOE
for
Risk
Assessment
Study
and
Toxicological
Effects
Acute
Dietary
An
acute
dietary
endpoint
was
not
identified
in
the
data
base
for
chlorine
dioxide.
This
risk
assessment
is
not
required.

Chronic
Dietary
NOAEL
=
3
mg/
kg/
day
UF
=
100
(
10x
interspecies
extrapolation,
10x
intra­
species
variation)

Chronic
PAD
=
0.03
mg/
kg/
day
Two­
generation
reproduction
toxicity
study
(
CMA,
1996)
­
decreases
in
absolute
brain
and
liver
weight,
and
lowered
auditory
startle
amplitude
at
LOAEL
of
6
mg/
kg/
day
Developmental
Toxicity
­
Rat
(
Orme
et
al.,
1985)­
neurobehavioral
and
exploratory
deficits
in
rat
pups
at
LOAEL
of
14
mg/
kg/
day
Incidental
Oral
(
short
and
intermediate
term)
NOAEL
=
3
mg/
kg/
day
MOE
=
100
See
summary
for
chronic
dietary
assessment
Page
19
of
49
Table
4.
Summary
of
Toxicological
Doses
and
Endpoint
Selection
for
Chlorine
dioxide/
Sodium
chlorite
Exposure
Scenario
Dose
Used
in
Risk
Assessment
(
mg/
kg/
day)
UF/
MOE
for
Risk
Assessment
Study
and
Toxicological
Effects
Short­
Term
Dermala
(
1­
30
days)
NOAEL
=
3
mg/
kg/
day
MOE
=
100
See
summary
for
chronic
dietary
assessment
Intermediate­
Term
Dermala
(
30­
days­
6
months)
NOAEL
=
3
mg/
kg/
day
MOE
=
100
See
summary
for
chronic
dietary
assessment
Long­
Term
Dermala
(
>
6
months)
NOAEL
=
3
mg/
kg/
day
MOE
=
100
See
summary
for
chronic
dietary
assessment
Inhalation
(
occupational
and
homeowner
short­
term)
Homeowner
shortterm
LOAEL
=
28
mg/
m3
(
10
ppm)
b
Occupational
exposure:
LOAEL
=
2.8
mg/
m3
(
1.0
ppm)
b
NOAEL
=
0.28
mg/
m3
(
0.1
ppm)
b.
Homeowner
shortterm
`
RfC'
=
0.14
mg/
m3
(
0.05
ppm)
b
Occupational
`
RfC'
=
0.009
mg/
m3
(
0.003
ppm)
b
Inhalation
toxicity
studies­
Rat
Dalhamn,
1957;
Paulet
and
Debrousses,
1970,
1972.

Inhalation
(
homeowner
long­
term)
Agency
RfC
methodology
used
to
derive
an
RfC
value
of
2
x
10­
4
mg/
m3
(
USEPA,
2000a)
(
Paulet
and
Desbrousses,
1970,
1972)
selected
as
co­
critical
studies
(
USEPA,
2000a)
a
Based
on
the
use
of
an
oral
endpoint
for
dermal
risk
assessments
and
the
lack
of
a
dermal
absorption
study,
a
dermal
absorption
value
of
100%
as
a
default
will
be
used.
b
Unit
conversion:
1
ppm
ClO2
x
67.46/
24.45
=
2.8
mg/
m3
3.4
Endocrine
Disruption
The
Food
Quality
Protection
Act
(
FQPA,
1996)
requires
that
EPA
develop
a
screening
program
to
determine
whether
certain
substances
(
including
all
pesticides
and
inerts)
"
may
have
an
effect
in
humans
that
is
similar
to
an
effect
produced
by
a
naturally
occurring
estrogen,
or
such
other
endocrine
effect ."
Following
the
recommendations
of
its
Endocrine
Disruptor
Screening
and
Testing
Advisory
Committee
(
EDSTAC),
EPA
determined
that
there
was
a
scientific
basis
for
including,
as
part
of
the
program,
the
androgen
and
thyroid
hormone
systems,
in
addition
to
the
estrogen
hormone
system.
EPA
also
adopted
EDSTAC's
recommendations
that
the
Program
include
evaluations
of
potential
effects
in
wildlife.
For
pesticide
chemicals,
EPA
will
use
FIFRA
and,
to
the
extent
that
effects
in
wildlife
may
help
determine
whether
a
substance
may
have
an
effect
in
humans,
FFDCA
authority
to
require
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
20
of
49
When
the
appropriate
screening
and/
or
testing
protocols
being
considered
under
the
Agency's
EDSP
have
been
developed,
chlorine
dioxide
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
Chlorine
dioxide
and
sodium
chlorite
are
active
ingredients
in
numerous
products
used
in
the
control
of
bacteria,
fungi,
and
algal
slimes.
Chlorine
dioxide
and
sodium
chlorite
are
also
used
as
material
preservatives
and
as
disinfectants.
At
this
time,
products
containing
chlorine
dioxide
and
sodium
chlorite
are
intended
for
agricultural
premises,
commercial,
industrial,
medical
and
residential
use.
The
agricultural
uses
include
the
disinfection
of
hard
surfaces
and
equipment
(
such
as
hatching
facilities
and
mushroom
houses)
and
water
systems
(
such
as
chiller
water
and
humidification
water
in
poultry
houses).
Commercial,
industrial,
and
medical
uses
include
disinfection
of
ventilation
systems,
hard
surfaces
(
e.
g.,
floors,
walls,
and
laboratory
equipment),
water
systems,
pulp/
paper
mills,
and
food
rinses.
Residential
uses
include
disinfection
of
hard
surfaces
(
e.
g.,
floors,
bathrooms),
HVAC
systems,
and
pool
&
spa
water
circulation
system
treatments.

4.2
Dietary
Exposure
and
Risk
A
detailed
dietary
exposure
risk
assessment
for
chlorine
dioxide
is
provided
in
the
Chlorine
Dioxide
Dietary
Risk
Assessment,
February
24,
2006.
The
summary
of
the
exposures
and
risks
are
presented
below.

The
Agency
has
carried
out
the
dietary
exposure
and
risk
assessment
for
use
of
chlorine
dioxide
in
products
used
in
the
control
of
bacteria,
fungi,
and
algal
slimes,
as
well
as
its
use
as
a
materials
preservative
and
disinfectant,
all
of
which
may
result
in
indirect
food
contact
exposures.
No
residue
chemistry
data
were
submitted
by
the
registrants,
nor
were
any
asked
for
by
the
Agency.
To
estimate
chlorine
dioxide
residues
on
food
due
to
migration
of
this
chemical
from
sanitizing
and/
or
disinfecting
hard
non­
porous
surfaces
which
can
come
into
contact
with
food,
the
Agency
has
used
FDA
(
US
Food
and
Drug
Administration)
methodology
as
well
as
a
methodology
established
for
use
in
the
Agency's
Reregistration
Eligibility
Decision
(
RED)
documents.
Potential
use
sites
include:
(
1)
mushroom
houses,
(
2)
poultry
hatcheries,
(
3)
food
handling
establishments,
(
4)
post­
harvest
potato
treatments,
(
5)
poultry
house
disinfection,
poultry
chiller
water/
carcass
spray
or
dip,
(
6)
food
processing
plants
(
meat
and
fish),
(
7)
dairies,
breweries,
and
bottling
plants,
and
(
8)
pulp/
paper,
polymer
slurries,
paper
adhesive,
and
paper
coating.

In
the
absence
of
residue
data
for
residues
of
chlorine
dioxide
on
treated
food
contact
surfaces,
the
Agency
estimated
residue
levels
that
may
occur
in
food
from
the
application
rates
on
food
contact
surfaces.
To
estimate
the
Estimated
Daily
Intake
(
EDI),
the
Agency
has
used
an
FDA
model.
The
maximum
application
rate
for
chlorine
dioxide
from
the
various
labeled
products
is
used
along
with
the
assumptions
that
food
can
contact
2000
cm2
of
treated
surfaces
and
an
assumption
that
10%
of
the
pesticide
migrates
to
food.
Page
21
of
49
The
dietary
risks
for
adult
and
children
are
shown
in
Table
6.
As
there
is
no
acute
dietary
endpoint
for
chlorine
dioxide,
only
chronic
dietary
risk
is
presented.
For
adults,
the
dietary
risk
is
23%
of
the
PAD.
For
children,
the
dietary
exposure
is
103%
of
the
PAD,
above
the
Agency's
level
of
concern
(
100%).

a­­
For
adults,
acute
and
chronic
exposure
analysis
is
based
on
a
body
weight
of
70
kg.
For
adult
females,
the
body
weight
is
60
kg.
For
children,
exposure
is
based
on
a
body
weight
of
15
kg.
b­­%
PAD
=
dietary
exposure
(
mg/
kg/
day)
*
100
/
cPAD,
where
cPAD
for
adults
and
children
=
0.03
mg/
kg/
day;
c­­
children
1­
2
years
of
age,
adults
20­
49
years
of
age
d­­
food
processing
plants
for
meats/
fish
have
exposures
which
are
similar
to
other
food
contact
surfaces,
exposure
numbers
not
included
for
this
scenario.
e­
­
includes
all
fruits
and
vegetables
and
apple
and
orange
juices.
Table
6.
Summary
of
Dietary
Exposure
and
Risk
for
Chlorine
Dioxide
Acute
and
Chronic
Dietary
Use
Site
Food
Type
Population
Subgroup
EDI
(
mg/
person/
day)
Dietary
Exposurea
(
mg/
kg/
day)
%
cPAD
b
Indirect
Food
Use
Adult
2.86E­
03
9.5
Food
handling
establishments/
kitchens
NA
Child
2.00
x
10­
1
1.33E­
02
44.4
Beverages,
alcoholic,
beer
Adult
1.2
x
10­
3
1.70E­
05
0.56
Adult
2.40E­
05
0.08
Beverages,
nonalcoholic
Child
1.6
x
10­
3
1.00E­
04
0.33
Adult
2.00E­
06
0.0086
Egg
Products,
Mayonnaise
Child
1.4
x
10­
4
9.33E­
06
0.031
Adult
2.70E­
04
0.66
Dairies,
Breweries,
Bottling
Plants,
Food
Contact
Surfaces/
Food
Processing
Plants
for
Meats
and
Fishd
Milk
Child
1.9
x
10­
2
1.30E­
03
4.2
Adult
1.1
x
10­
1
1.54E­
03
5.1
Pulp/
Paper,
Polymer
Slurries,
Paper
Adhesive,
Paper
Coating
NA
Child
5.3
x
10­
2
3.55E­
03
11.8
Adult
3.3
x
10­
1
4.71E­
03
15.7
Total
Indirect
Food­
Contact
Exposure
Child
2.7
x
10­
1
1.83E­
02
61.0
Direct
Food
Use
Adult
2.24E­
03c,
e
7.5
Fruit
and
Vegetable
Wash
Child
1.27E­
02
c,
e
42.3
Adult
2.24E­
03
7.5
Total
Direct
Food­
Contact
Exposure
Child
1.27E­
02
42.3
Total
Dietary
Exposure
Adult
6.95E­
03
23.2
Total
Direct
and
Indirect
Food­
Contact
Exposure
Child
3.10E­
02
103.3
Page
22
of
49
In
the
poultry
hatcheries,
eggs
are
produced
for
the
production
of
chicks
and
not
for
human
consumption.
Although
it
is
likely
some
sanitizer/
disinfectant
chemicals
may
penetrate
the
egg
shells
and
bioaccummulate
in
the
developing
chicks,
at
this
time
the
Agency
believes
that
the
amount
of
the
chemical
transferred
to
the
developing
chicks
is
not
likely
to
adversely
affect
the
development
of
chicks
and
will
have
an
even
smaller
transfer
into
humans.
The
Agency
has
no
dietary
risk
concerns
at
this
time
for
this
use.

Similarly,
the
Agency
has
no
concerns
at
this
time
for
use
of
chlorine
dioxide
and
sodium
chlorite
for
stored
potato
treatment
and
subsequent
interstate
commerce
of
this
commodity.
EPA's
Antimicrobials
Division
had
asked
the
States
of
Idaho
and
Washington
to
collect
analytical
data
on
the
residues
on
chlorine
dioxide
treated
post­
harvest
potatoes
(
USEPA,
1998).
Two
breakdown
products
of
chlorine
dioxide
were
measured,
chlorite
and
chlorate.
Chlorite
was
found
to
be
non­
detect
in
the
samples
and
only
small
quantities
of
chlorate
(
0.97
to
1.1
µ
g/
g)
were
found
in
only
three
samples.
The
Agency
did
not
see
any
concerns
for
the
presence
of
chlorate
at
the
levels
reported
in
the
samples.

For
poultry
house
disinfection
and
poultry
chiller
water/
carcass
spray
or
dip,
the
application
and
method
of
application
is
exactly
the
same
as
was
submitted
to
FDA
for
their
risk
assessment.
FDA
assessed
the
risks
involved
for
this
use
(
FDA
Memo:
FAP:
4A4433,
1994).
FDA
extensively
reviewed
the
efficacy
and
analytical
chemistry
data
on
the
residues
of
chlorate/
chlorite
or
possibly
chlorine
dioxide
for
the
scenarios
listed.
Residues
of
chlorite
and
chlorates
were
measured
on
poultry
carcasses
after
pre­
chiller
and
chiller
water
treatments.
After
the
pre­
chiller,
neither
chlorite
nor
chlorate
was
detected
between
0.009
ppm
to
0.011
ppm
levels
of
detection.
In
the
chiller
water
treatment,
chlorite
detection
was
at
0.54
ppm
at
time
zero,
0.09
ppm
at
10
minutes
and
at
0.021
ppm
after
one
hour.
The
level
of
detection
(
LOD)
was
set
at
0.016
ppm.
Chlorite
was
non­
detect
after
2
hours.
Chlorate
was
non­
detect
even
at
time
zero.
It
is
likely
that
the
residual
chlorate/
chlorite
associated
with
the
poultry
may
be
going
through
oxidative
processes
to
form
chlorinated
organics.
FDA
asked
the
industry
to
conduct
studies
on
the
formation
of
chlorinated
organics,
and
no
evidence
was
found
for
the
formation
of
chlorinated
organics.
However,
some
PCBs
were
detected
at
the
background
levels.
Open
literature
studies
support
the
results
that
with
acidified
sodium
chlorate
treatment
of
poultry
no
chlorinated
organics
are
formed.
FDA
accepted
the
studies
and
concurred
with
the
results.
At
this
time,
the
Agency
does
not
have
any
concerns
with
the
use
of
acidified
sodium
chlorite
solution
on
carcasses.

For
food
processing
plants
(
meat
and
fish),
the
application
rates
are
similar
to
those
used
for
food
handling
establishments,
and
therefore,
the
exposure
would
also
be
similar.
At
this
time,
the
Agency
does
not
have
any
dietary
concerns
for
this
application.

The
Agency,
at
this
time,
has
not
established
any
tolerances
or
exemptions
from
the
requirement
of
tolerance
for
chlorine
dioxide
on
mushroom
uses.
No
residue
data
has
been
submitted
to
the
Agency
for
this
use.
The
Agency
has
not,
at
this
time,
conducted
any
dietary
risk
assessment
for
mushroom
use
of
chlorine
dioxide.
Page
23
of
49
FDA
assumptions
were
used
to
calculate
the
dietary
exposure
from
sanitizing
foodcontact
surfaces;
processing
equipments;
and
utensils
in
dairies,
breweries,
canning
operations,
and
meat
and
vegetable
processing
plants.
Based
on
these
assumptions
and
data
on
alcoholic
beverages/
beer,
non­
alcoholic
beverages,
egg
products,
and
salad
dressing/
mayonnaise,
the
highest
%
cPAD
calculated
is
4.2%
for
children's
consumption
of
milk.

In
addition,
AD
performed
an
exposure
assessment
on
chlorine
dioxide's
slimicide
use
in
paper/
pulp,
paper
coatings,
polymer
slurries
(
as
a
filler
in
paper),
and
paper
adhesives.
With
paper
adhesives
being
the
largest
contribution,
the
cumulative
risk
from
these
uses
is
11.8%
of
the
cPAD
in
children
and
5.13%
in
adults.

For
direct
food
uses,
AD
conducted
a
chronic
risk
assessment
for
the
fruit
and
vegetable
washes
(
post­
harvest)
and
the
chronic
risk
from
these
uses
appear
to
be
below
the
Agency's
level
of
concern.

Table
7.
Exposure
by
Population
Group
Population
Subgroup
Total
exposure
(
mg/
kg
body
wt./
day)
%
cPAD
U.
S.
Population
0.003292
11
Infants
<
1
year
0.003493
12
Children
1­
6
years
0.009933
33
Children
7­
12
years
0.004208
14
Females
13­
50
0.002689
9
4.3
Drinking
Water
Exposures
and
Risks
In
a
memo
from
Pat
Fair
of
the
EPA's
Office
of
Water,
exposure
to
chlorine
dioxide
from
drinking
water
was
characterized.
Chlorine
dioxide
is
used
as
a
disinfectant
in
water
treatment
plants
in
the
USA.
Chlorite
ions
(
ClO2)
are
present
in
drinking
water
as
a
result
of
reactions
involving
chlorine
dioxide.
Because
of
the
health
concerns
resulting
from
the
presence
of
the
chlorite
ions
and
their
subsequent
conversion
to
chlorate
ions,
the
Agency
wanted
to
make
sure
that
the
level
of
chlorite
ions
did
not
exceed
certain
specified
limits.
The
EPA
instituted
a
system
for
monitoring
the
occurrence
of
chlorite
in
drinking
water
and
collected
data
from
July
1997
to
December
1998.

Based
on
the
results
of
this
monitoring
data,
the
Agency
established
a
Stage
I
Disinfectants
and
Disinfection
Byproduct
Rule,
which
established
a
maximum
contaminant
level
goal
(
MCLG)
and
a
maximum
contaminant
level
(
MCL)
for
chlorite
ions.
The
MCLG
and
MCL
are
0.8mg/
L
and
1.0
mg/
L,
respectively.
Based
on
the
values
obtained
from
the
monitoring
data,
the
Agency
conducted
a
drinking
water
assessment
using
chlorite
concentrations
at
the
maximum,
90th
percentile,
and
median
annual
averages
of
chlorite
concentrations
of
0.700,
0.630,
and
0.390
mg/
L,
respectively.
The
DEEM­
FCID
 
,
Version
2.0
software
(
EPA,
2000)
was
used
to
determine
the
exposure
values
(
Memo
from
David
Hrdy,
HED,
to
Jennifer
Slotnick,
AD).
Table
8
presents
the
exposures
and
corresponding
risks.
The
90th
percentile
exposure
values
will
be
used
in
the
aggregate
risk
assessments,
with
children
represented
by
the
1­
6
year
old
age
category.
The
only
subpopulation
that
the
Agency
has
concerns
for
is
infants
(
less
than
one
year
old)
when
exposed
to
chlorine
dioxide
treated
water.
All
other
subpopulations
and
the
Page
24
of
49
general
population
have
risks
below
the
Agency's
level
of
concern.

Table
8.
Chlorite
Exposure
by
Population
Group
Maximum
Concentration
90th
Percentile
Concentration
Median
Concentration
Population
subgroup
Total
exposure
(
mg/
kg/
day)
%
cPAD
Total
exposure
(
mg/
kg/
day)
%
cPAD
Total
exposure
(
mg/
kg/
day)
%
cPAD
U.
S.
Population
0.014754
49
0.013279
44
0.008220
27
Infants
<
1
year
0.048372
161
0.043535
145
0.026950
90
Children
1­
6
years
0.020613
69
0.018552
62
0.011485
38
Children
7
­
12
years
0.013402
45
0.012062
40
0.007467
25
Females
13­
50
0.014274
48
0.012846
43
0.007952
27
4.4
Residential
Exposure/
Risk
Pathway
A
detailed
human
exposure
risk
assessment
for
chlorine
dioxide
is
provided
in
the
attached
Appendix.
The
summary
of
the
exposures
and
risks
to
the
residential
population
are
presented
below.

4.4.1
Residential
Handler
Scenarios
Exposure
Scenarios
Chlorine
dioxide
and
sodium
chlorite
are
active
ingredients
in
numerous
products
used
in
the
control
of
bacteria,
fungi,
and
algal
slimes.
In
addition,
chlorine
dioxide
and
sodium
chlorite
are
used
as
material
preservatives
and
as
disinfectants.
Residential
uses
of
chlorine
dioxide
and/
or
sodium
chlorite
products
that
are
applied
by
homeowners
include
the
control
of
mold
and
mildew
(
i.
e.,
EPA
Reg.
No.
21164­
3).
For
the
exposure
assessment,
household
cleaning
products
were
grouped
together
to
be
represented
by
a
higher
application
rate
from
a
sodium
chlorite
product
(
i.
e.,
EPA
Reg.
No.
21164­
3).
The
post
application
scenario
is
based
on
a
product
that
applies
chlorine
dioxide
to
floors
that
have
the
potential
for
children
playing.
Three
scenarios,
mopping,
spraying,
and
placing
tablets
in
pools/
spas,
were
examined
to
represent
the
residential
uses
in
the
risk
assessment.

Exposure
Data
and
Assumptions
There
are
no
chemical­
specific
exposure
data
to
assess
applications
to
hard
surfaces
with
a
mop
or
trigger­
pump
sprayer
or
to
pools/
spas.
However,
surrogate
data
are
available.
Dermal
exposures
were
assessed
using
the
proprietary
Chemical
Manufacturers
Association
(
CMA)
data
(
MRID
42587501)
for
mopping
as
well
as
placing
tablets
in
pools/
spas
and
the
Pesticide
Handler
Exposure
Database
(
PHED,
1998)
for
spraying.
The
CMA
data
for
mopping
are
based
on
individuals
mopping
floors
and
receiving
exposure
via
contact
with
the
mop
or
with
the
bucket.
Dermal
exposures
were
assessed
for
trigger
pump
spray
application
methods
using
PHED
Version
1.1
values
found
in
the
Residential
Exposure
SOPs
(
USEPA,
2000b).
The
surrogate
exposure
data
in
PHED
are
based
on
test
subjects
applying
an
insecticide
from
an
aerosol
can
to
Page
25
of
49
baseboards
in
kitchens.
The
dermal
exposures
from
these
techniques
have
been
normalized
by
the
amount
of
active
ingredient
handled
and
reported
as
unit
exposures
(
UE)
expressed
as
mg/
lb
ai
handled.

In
addition,
product
label
maximum
application
rates,
related
use
information,
and
Agency
standard
values
were
used
to
assess
residential
handler
exposures.
For
example,
it
was
assumed
that
one
gallon
of
diluted
solution
is
used
for
mopping
floors,
while
0.5
liters
(
0.13
gallons)
are
used
in
the
trigger
pump
spray
scenario.
The
residential
handler
scenarios
are
assumed
to
be
of
short­
term
duration
(
1­
30
consecutive
days).

Risk
Characterization
A
summary
of
the
dermal
residential
handler
exposures
and
risks
are
presented
in
Table
9.
Although
the
dermal
endpoint
represents
short­,
intermediate­,
and
long­
term
durations,
the
exposure
duration
of
most
homeowner
applications
of
cleaning
products
is
believed
to
be
best
represented
by
the
short­
term
duration.
The
toxicological
endpoint
is
based
on
an
oral
study
and
no
dermal
absorption
value
is
available.
Therefore
100%
dermal
absorption
was
assumed.
The
calculated
dermal
MOEs
are
above
the
target
MOE
of
100
for
both
of
the
cleaning
scenarios.
The
dermal
MOE
for
applications
to
hard
surfaces
via
trigger­
pump
sprayer
is
3,200
and
the
dermal
MOE
for
application
of
liquid
formulations
via
mopping
is
1,300.
However,
the
dermal
MOE
for
the
placement
of
tablets
into
pools
is
46,
and
therefore,
of
concern.
This
risk
can
be
mitigated
with
the
use
of
gloves
(
MOE=
500).

Table
9.
Estimates
of
Short­
term
Dermal
Exposures
and
Risks
to
Residential
Handlers
of
Chlorine
Dioxide
Product
Exposure
Scenario
Potential
Dermal
Dosea
(
mg/
kg/
day)
Dermal
MOEb
(
Target
MOE
=
100)

Mopping
­
hard
surfaces
0.095
1300
Cleaning
Trigger­
pump
sprayer
­
hard
surfaces
0.038
3200
Swimming
Pools
Solid
Place
(
tablets)
0.065
(
no
gloves)
0.006
(
gloves)
46
(
no
gloves)
500
(
gloves)

a
Potential
Dermal
Dose
(
mg/
kg/
day)
=
Application
Rate
(
lb
ai/
gallon)
*
gallons
used
*
Dermal
Unit
Exposure
(
mg/
lb
ai)
)/
Body
Weight
(
60
kg),
where
dermal
absorption
is
100
percent.
b
Dermal
MOE=
Dermal
NOAEL
(
3
mg/
kg/
day)/
Absorbed
Dermal
Dose
(
mg/
kg/
day).

The
potential
inhalation
of
chlorine
dioxide
may
occur
from
off
gassing
during
application
of
the
aqueous
solution.
Chlorine
dioxide
has
the
potential
to
generate
a
gas
during
the
residential
uses
of
mopping
and
spraying.
However,
it
is
unlikely
that
levels
of
concern
for
chlorine
dioxide
would
be
generated
outdoors
while
treating
swimming
pools
&
spas
with
tablets
placed
into
water.

EFAST
(
Exposure
and
Fate
Assessment
Screening
Tool)
was
used
to
model
the
air
concentration
from
general
purpose
cleaners
(
http://
www.
epa.
gov/
opptintr/
exposure/).
The
peak
instantaneous
air
concentration
is
0.265
mg/
m3
(
0.09
ppm)
and
the
average
daily
TWA
(
time
Page
26
of
49
weighted
average)
air
concentration
is
determined
to
be
0.00794
mg/
m3
(
0.003
ppm).
The
residential
short­
term
inhalation
endpoint
(
RfC)
is
0.05
ppm.
Based
on
the
average
daily
air
concentration
(
representing
both
application
and
post
application),
the
handler
inhalation
exposures
of
chlorine
dioxide
are
not
of
concern
(
i.
e.,
the
average
air
concentration
estimated
by
EFAST
of
0.003
ppm
is
below
the
RfC
of
0.05
ppm).

4.4.2
Residential
Post
Application
Exposure
Residential
post
application
exposures
result
when
bystanders
(
adults
and
children)
come
in
contact
with
chlorine
dioxide
in
areas
where
pesticide­
treated
end­
use
products
have
recently
been
applied
(
e.
g.,
treated
hard
surfaces/
floors),
or
when
children
incidentally
ingest
the
pesticide
residues
through
mouthing
the
treated
end
products/
treated
articles
(
i.
e.,
hand­
tomouth
or
object­
to­
mouth
contact).
Because
of
the
high
vapor
pressure
of
chlorine
dioxide,
inhalation
exposure
to
chlorine
dioxide
off
gassing
is
also
a
potential
route
of
exposure.

For
the
purposes
of
this
screening­
level
assessment,
four
scenarios
have
been
considered.
These
include:
(
1)
exposure
to
residue
from
hard
floors
that
have
been
cleaned/
mopped
with
a
generic
cleaner
containing
chlorine
dioxide,
(
2)
exposure
to
chlorine
dioxide
used
to
clean
residential
HVAC
systems,
(
3)
exposure
to
a
continuous
release
(
gas)
deodorizer,
and
(
4)
swimming.

Exposure
Data
and
Assumptions
Typically,
most
products
used
in
a
residential
setting
result
in
exposures
occurring
over
short­
term
time
duration
(
1
 
30
days).
If
the
products
are
used
on
a
routine
basis
(
i.
e.,
once
a
week)
and
the
active
ingredient
has
a
long
indoor
half­
life,
exposures
may
occur
over
an
intermediate­
term
time
duration
(
30
days
 
6
months).
At
this
time,
AD
does
not
have
residue
dissipation
data
or
reliable
use
pattern
data,
including
the
frequency
and
duration
of
use
of
antimicrobial
products
in
the
residential
setting.
Even
though
AD
does
not
believe
that
the
use
patterns
of
many
residential
products
result
in
intermediate­
term
exposure,
they
are
assessed
to
provide
an
upper
bound
estimate
of
exposure.
AD
does
believe,
however,
that
intermediateterm
exposure
to
children
may
occur
in
day
care
centers
where
disinfecting
products
are
used
more
frequently.

A
number
of
conservative
assumptions
were
used
in
assessing
post
application
risks
including
maximum
application
rates
from
the
label.
In
addition,
quantities
handled/
treated
were
estimated
based
on
information
from
various
sources,
including
the
Draft
Standard
Operating
Procedures
(
SOPs)
for
Residential
Exposure
Assessments
(
USEPA
2000b).
In
certain
cases,
no
standard
values
were
available
for
some
scenarios.
Assumptions
for
these
scenarios
were
based
on
AD
estimates
and
could
be
further
refined
from
input
from
affected
sectors.

Risk
Characterization
A
summary
of
the
residential
dermal
and
oral
post
application
exposures
and
risks
are
presented
in
Table
10.
The
child
short­
and
intermediate­
term
dermal
MOE
for
contact
Page
27
of
49
following
hard
surface
disinfection
is
above
the
target
MOE
of
100
for
residential
and
daycare
settings
(
MOE
=
280).
The
short­
and
intermediate­
term
incidental
oral
MOE
following
hard
surface
disinfection
is
above
the
target
MOE
of
100
for
residential
and
daycare
settings
(
MOE
=
2,300),
and
thus
is
not
of
concern.

Inhalation
exposures
due
to
post
application
activities
could
occur
for
children
after
the
treatment
of
floors;
adults
and
children
after
the
treatment
of
HVAC
systems;
and
adults
and
children
after
the
use
of
continuous
release
(
gas)
deodorizers.
Chlorine
dioxide
and/
or
sodium
chlorite
can
be
applied
as
an
aqueous
solution
to
hard
surfaces
such
as
floors
(
as
well
as
dust
applications
to
carpets).
Based
on
the
use
label,
which
contains
the
highest
rate
of
application
of
chlorine
dioxide
to
disinfect
a
room,
and
using
several
assumptions,
the
maximum
air
concentration
of
chlorine
dioxide
can
be
estimated.
Two
methods
were
used
to
assess
the
inhalation
risks
to
residents.
First,
there
are
air
concentration
measurements
available
after
the
application
of
chlorine
dioxide
as
a
dust
treatment
on
carpets
(
Speronello
2005).
Although
there
are
limitations
to
this
study
(
e.
g.,
not
conducted
under
Good
Laboratory
Practices
(
GLPs),
minimal
information
is
available
in
the
study
report),
it
is
the
only
data
source
available
at
this
time.
Secondly,
a
theoretical
approach
to
estimating
chlorine
dioxide
air
concentration
is
also
presented
based
on
dilution
and
ventilation
along
with
the
half­
life
of
chlorine
dioxide.
Based
on
these
estimates,
an
8­
hour
TWA
air
concentration
starting
immediately
after
application
has
been
determined
to
be
0.08
ppm
which
is
above
the
short­
term
RfC
of
0.05
ppm.
To
mitigate
this
risk
concern,
a
second
8­
hour
TWA
air
concentration
was
calculated
assuming
a
1­
hour
restricted
entry
interval
(
REI).
If
one
could
assume
that
residents
would
stay
out
of
the
house
for
the
first
hour,
the
8­
hour
TWA
is
0.02
ppm
which
is
below
the
RfC
of
0.05
ppm.
To
accurately
determine
the
initial
concentration
of
chlorine
dioxide
in
the
air
after
mopping,
air
monitoring
data
would
be
needed.

For
HVAC
systems,
BCI
(
2002)
monitored
a
chlorine
dioxide
treatment
of
a
HVAC
system
in
a
residence.
The
air
concentrations
monitored
indicated
a
maximum
value
of
0.02
ppm
and
the
average
value
was
below
the
detection
limit
of
0.01
ppm.
The
short­
term
inhalation
RfC
for
chlorine
dioxide
is
0.05
ppm.
According
to
the
label,
the
frequency
of
HVAC
system
treatments
is
to
"
treat
as
required."
The
frequency
of
residential
(
and/
or
commercial/
intuitional)
HVAC
treatments
is
expected
to
be
minimal
(
most
likely
less
than
once
per
year).
In
addition,
the
half­
life
of
chlorine
dioxide
is
rapid.
Therefore,
inhalation
exposure
is
expected
to
be
limited
to
short­
term
durations
and
inhalation
risks
are
not
expected
to
be
a
concern.

For
the
continuous
release
deodorizers,
a
bounding
estimate
of
air
concentration
is
presented
based
on
the
application
rate
and
the
label­
referenced
longevity
of
the
pouches/
sachets.
The
theoretical
constant
air
concentration
would
be
0.52
ppm
assuming
no
air
exchange
and
no
build
up
of
chlorine
dioxide
over
time
because
of
the
short
half­
life.
The
RfC
for
long­
term
continuous
exposure
is
0.00007
ppm.
Therefore,
the
theoretical
concentration
from
the
product's
release
is
of
concern.
This
bounding
estimate
can
be
refined
by
determining
residential
(
and
commercial/
institutional)
ventilation
rates,
identifying
sensitive
analytical
detection
methods
and
collecting
monitoring
data,
and
determining
the
number
of
hours
an
individual
is
exposed
in
treatment
areas.
However,
before
any
refinements
to
these
air
concentration
estimates
are
attempted,
it
should
be
determined
if
the
product's
efficacy
can
be
maintained
at
the
RfC
of
Page
28
of
49
~
0.00007
ppm.

Table
10.
Summary
of
Short­
and
Intermediate­
Term
Residential
Postapplication
Exposures
and
Risks
Scenario
Dose
a
(
mg/
kg/
day)
MOEb
(
Target
MOE>
100
dermal
and
oral)

Dermal
Exposure
Hard
surface
Disinfection
Residential
Setting
and
Daycare
center
0.017
280
Incidental
Oral
Exposure
Hard
surface
Disinfection
Residential
Setting
and
Daycare
center
0.0013
2,300
a
Dose
calculations
for
each
scenario
above
are
outlined
in
the
attached
Occupational/
Residential
Assessment.
b
MOE=
NOAEL
(
mg/
kg/
day)
/
Dose
(
mg/
kg/
day).
Oral
and
dermal
NOAEL
is
3
mg/
kg/
day.

5.0
AGGREGATE
RISK
ASSESSMENTS
AND
RISK
CHARACTERIZATIONS
In
order
for
a
pesticide
registration
to
continue,
it
must
be
shown
that
the
use
does
not
result
in
"
unreasonable
adverse
effects
on
the
environment".
Section
2
(
bb)
of
FIFRA
defines
this
term
to
include
"
a
human
dietary
risk
from
residues
that
result
from
a
use
of
a
pesticide
in
or
on
any
food
inconsistent
with
standard
under
section
408..."
of
FFDCA.
Consequently,
even
though
no
pesticide
tolerances
have
been
established
for
chlorine
dioxide,
the
standards
of
FQPA
must
still
be
met,
including
"
that
there
is
reasonable
certainty
that
no
harm
will
result
from
aggregate
exposure
to
pesticide
chemical
residue,
including
all
anticipated
dietary
exposures
and
other
exposures
for
which
there
are
reliable
information."
Aggregate
exposure
is
the
total
exposure
to
a
single
chemical
(
or
its
residues)
that
may
occur
from
dietary
(
i.
e.,
food
and
drinking
water),
residential,
and
other
non­
occupational
sources,
and
from
all
known
or
plausible
exposure
routes
(
oral,
dermal,
and
inhalation).
Aggregate
risk
assessment
were
conducted
for
acute
(
1
day),
short­
term
(
1­
30
days),
intermediate­
term
(
1­
6
months)
and
chronic
(
several
months
to
lifetime)
exposures.

In
performing
aggregate
exposure
and
risk
assessments,
the
Office
of
Pesticide
Programs
has
published
guidance
outlining
the
necessary
steps
to
perform
such
assessments
(
General
Principles
for
Performing
Aggregate
Exposure
and
Risk
Assessments,
November
28,
2001;
available
at
http://
www.
epa.
gov/
pesticides/
trac/
science/
aggregate.
pdf).
Steps
for
deciding
whether
to
perform
aggregate
exposure
and
risk
assessments
are
listed,
which
include:
identification
of
toxicological
endpoints
for
each
exposure
route
and
duration;
identification
of
potential
exposures
for
each
pathway
(
food,
water,
and/
or
residential);
reconciliation
of
durations
and
pathways
of
exposure
with
durations
and
pathways
of
health
effects;
determination
of
which
possible
residential
exposure
scenarios
are
likely
to
occur
together
within
a
given
time
frame;
determination
of
magnitude
and
duration
of
exposure
for
all
exposure
combinations;
determination
of
the
appropriate
technique
(
deterministic
or
probabilistic)
for
exposure
Page
29
of
49
assessment;
and
determination
of
the
appropriate
risk
metric
to
estimate
aggregate
risk.

5.1
Acute
and
Chronic
Aggregate
Risks
The
acute
and
chronic
aggregate
risk
assessments
include
only
dietary
and
drinking
water
exposures.
An
acute
risk
assessment
was
not
conducted
for
chlorine
dioxide
because
there
were
no
acute
dietary
endpoints
of
concern.
Drinking
water
exposure
estimates
are
presented
in
Section
4.3.
Acute
and
chronic
dietary
risk
estimates
from
direct
and
indirect
food
uses
are
presented
in
Table
6
of
Section
4.2.
Table
11
presents
a
summary
of
these
exposures,
including
the
aggregate
dietary
exposure
(
all
direct
and
indirect
food
contact
exposures)
as
well
as
a
total
dietary
aggregate
exposure
value
(
drinking
water
plus
direct/
indirect
dietary
exposures).

Table
11.
Chlorine
Dioxide
Chronic
Aggregate
Exposures
and
Risks
Chronic
Dietary
Exposures
(
mg/
kg/
day)

Exposure
Routes
Dietary
(
indirect
+
direct
food
contact)
Exposuresa
Drinking
water
exposures
Aggregate
Dietary
Exposuresb
Aggregate
Dietary
Risks
(%
cPAD)

Adults
Oral
Ingestion
6.95E­
03
1.33E­
02
2.02E­
02
67%
Children
Oral
Ingestion
3.10E­
02
1.86E­
02
4.95E­
02
165%
a
Dietary
(
indirect
+
direct
food
contact)
exposures
=
sum
of
dietary
exposures
presented
in
Table
6.
b
Aggregate
Dietary
Exposures
=
sum
of
both
dietary
(
direct
and
indirect
food
contact)
exposures
and
drinking
water
exposures.

5.2
Short­
and
Intermediate­
Term
Aggregate
Exposures
and
Risks
Short­
and
intermediate­
term
aggregate
exposures
and
risks
were
assessed
for
adults
and
children
that
could
be
exposed
to
chlorine
dioxide
residues
from
the
use
of
products
in
nonoccupational
environments.
The
following
list
summarizes
all
of
the
potential
sources
of
chlorine
dioxide
exposures
for
adults
and
children.

Adult
chlorine
dioxide
exposure
sources:

handling
of
cleaning
products
containing
chlorine
dioxide
as
an
active
ingredient
during
wiping
activities;

handling
of
cleaning
products
containing
chlorine
dioxide
as
an
active
ingredient
during
mopping
activities;

eating
food
having
chlorine
dioxide
residues
from
use
of
product
on
fruits
and
vegetables;

eating
food
having
chlorine
dioxide
residues
from
indirect
food
contact;
and

drinking
water
containing
chlorine
dioxide.

Child
chlorine
dioxide
exposure
sources:

post­
application
exposures
to
cleaning
product
residues
containing
chlorine
dioxide
as
an
active
used
on
hard
surfaces
(
i.
e.,
floors);

eating
food
having
chlorine
dioxide
residues
from
use
of
product
on
fruits
and
Page
30
of
49
vegetables;

eating
food
having
chlorine
dioxide
residues
from
indirect
food
contact;
and

drinking
water
containing
chlorine
dioxide.

The
use
patterns
of
the
products
and
probability
of
co­
occurrence
must
be
considered
when
selecting
scenarios
for
incorporation
in
the
aggregate
assessment.
Table
12
summarizes
the
scenarios
included
in
the
short­
and
intermediate­
term
aggregate
assessments.

Table
12.
Exposure
Scenarios
Included
in
the
Aggregate
Assessments
Short­
term
Aggregate
Intermediate­
Term
Aggregate
Adults

chronic
dietary
(
direct
and
indirect)

handling
cleaning
products
 
spray
(
dermal
only)

handling
cleaning
products
 
mopping
(
dermal
only)

chronic
drinking
water
N/
A
Children

chronic
dietary
 
(
direct
and
indirect)

post­
app
to
cleaning
product
(
dermal
and
oral)

chronic
drinking
water

chronic
dietary
 
(
direct
and
indirect)

post
application
to
cleaning
product
(
dermal
and
oral)

chronic
drinking
water
The
chronic
dietary
exposures
were
used
in
both
the
short­
and
intermediate­
term
aggregate
assessment
because
chronic
dietary
exposures
occur
nearly
every
day
(
as
opposed
to
acute
dietary
exposures
occurring
on
a
one­
time
basis).
Therefore,
short­
or
intermediate­
term
non­
dietary
exposures
have
a
much
higher
probability
to
co­
occur
with
the
chronic
dietary
intake
rather
than
the
acute
dietary
intake.

Cleaning
activities
in
a
residential
setting
occur
on
a
short­
term
basis.
However,
the
chlorine
dioxide­
containing
cleaning
products
are
also
labeled
for
use
in
institutional
settings
such
as
day­
care
facilities
where
cleaning
activities
can
occur
on
an
intermediate­
term
basis.
Therefore,
children
could
have
exposure
to
cleaning
product
residues
on
a
more
continuous
basis
in
a
day
care
facility,
thus,
these
post
application
scenarios
were
included
in
the
intermediateterm
aggregate
assessment.

Since
the
toxicity
endpoints
for
the
oral
and
dermal
routes
of
exposure
are
based
on
the
same
study
and
same
toxic
effect,
these
two
routes
are
aggregated
together.
Aggregate
risks
were
calculated
using
the
total
MOE
approach
outlined
in
OPP
guidance
for
aggregate
risk
assessment
(
August
1,
1999,
Updated
"
Interim
Guidance
for
Incorporating
Drinking
Water
Exposure
into
Aggregate
Risk
Assessments").
Table
13
presents
a
summary
of
both
dietary
and
dermal
exposures.
Table
14
presents
a
summary
of
the
short­
and
intermediate­
term
aggregate
risk
MOEs.
The
aggregate
risks
are
not
of
concern
for
adults,
as
the
total
aggregate
MOE
is
130,
which
is
above
the
target
of
100.
For
children,
the
aggregate
risk
estimates
are
below
the
target
MOE
of
100
(
MOE=
44)
and
thus
are
of
concern.
It
should
be
noted
that
several
conservative
assumptions
were
used
in
this
assessment.
Page
31
of
49
Table
13.
Doses
for
Short­
and
Intermediate­
term
Aggregate
Assessment
Dermal
Exposures
(
mg/
kg/
day)
Hard
Surface
Cleaning
Applicator
Exposure
Routes
Aggregate
Dietary
Exposures
(
mg/
kg/
day)
Mop
Spray
Post­
Application
Adults
Oral
Ingestion
2.0E­
02
NA
NA
NA
Dermal
NA
0.0024
0.00095
NA
Children
Oral
Ingestion
5.0E­
02
NA
NA
0.0013
Dermal
NA
NA
NA
0.017
Table
14.
Short­
and
Intermediate­
term
Aggregate
Risks
(
MOEs)
Dermal
Risks
(
MOE)
Hard
Surface
Cleaning
Applicator
Exposure
Routes
Aggregate
Dietary
Risks
Mop
Spray
Post­
Application
Aggregate
Risks
(
MOE)

Adults
Oral
Ingestion
MOEs
150
NA
NA
NA
150
Dermal
MOEs
NA
1300
3200
NA
900
Total
MOE
150
1300
3200
NA
130
Children
Oral
Ingestion
MOEs
60
NA
NA
2300
100
Dermal
MOEs
NA
NA
NA
180
180
Total
MOE
60
NA
NA
160
44
MOE
=
NOAEL/
dose
Aggregate
MOE
=
1/((
1/
MOEdietary)
+
(
1/
MOEdrinking
water)
+
(
1/
MOEdermal)
All
NOAELs
=
3
mg/
kg/
day
Target
MOE
oral
=
100
Target
MOE
dermal
=
100
6.0
CUMULATIVE
RISK
Section
408
of
the
FFDCA
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
Page
32
of
49
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.

EPA
has
not
assumed
that
chlorine
dioxide
has
a
common
mechanism
of
toxicity
with
other
substances.
For
information
regarding
EPA's
efforts
to
determine
which
chemicals
have
a
common
mechanism
of
toxicity
and
to
evaluate
the
cumulative
effects
of
such
chemicals,
see
the
policy
statements
released
by
EPA's
Office
of
Pesticide
Programs
concerning
common
mechanism
determinations
and
procedures
for
cumulating
effects
from
substances
found
to
have
a
common
mechanism
on
EPA's
website
at
http://
www.
epa.
gov/
pesticides/
cumulative/.

7.0
OCCUPATIONAL
EXPOSURE
A
detailed
human
exposure
risk
assessment
for
chlorine
dioxide
is
provided
in
the
attached
Appendix.
The
summary
of
the
exposures
and
risks
to
occupational
workers
are
presented
below.

7.1
Occupational
Handler
Potential
occupational
handler
exposure
from
the
use
of
chlorine
dioxide
products
can
occur
in
various
use
sites,
including
agricultural
premises,
food
handling,
commercial
and
institutional
premises,
medical
premises,
human
drinking
water
systems,
industrial
processes
and
water
systems,
application
to
material
preservatives,
and
swimming
pools
and
other
aquatic
areas.
The
occupational
exposure
scenarios
and
estimated
risks
are
presented
in
Table
15.
Exposure
estimates
for
the
fruits
and
vegetable
wash
and
the
machinists
exposed
to
treated
metal
working
fluids
(
MWF)
are
presented
separately.

To
assess
the
handler
risks,
AD
used
surrogate
unit
exposure
data
from
both
the
proprietary
Chemical
Manufacturers
Association
(
CMA)
antimicrobial
exposure
study
and
the
Pesticide
Handlers
Exposure
Database
(
PHED).
Inhalation
handler
exposures
were
combined
with
post
application
exposures
to
represent
a
"
full­
day"
or
8­
hour
time
weighted
average
(
TWA)
to
be
comparable
to
the
inhalation
RfC.
Inhalation
exposure
to
the
release
of
chlorine
dioxide
gas
during
the
mixing/
loading/
application
of
products
producing
chlorine
dioxide
may
occur.
Because
the
inhalation
toxicological
endpoint
is
based
on
an
8­
hour
TWA,
the
assessment
of
handler
inhalation
exposures
is
assessed
as
a
combination
of
activities
throughout
a
work
day.
The
assessment
of
inhalation
exposure
is
presented
in
the
post
application/
bystander
section
For
the
occupational
handler
dermal
risk
assessment,
the
short­
and
intermediate­
term
risks
calculated
at
baseline
exposure
(
no
gloves
and
no
respirators)
were
above
target
MOEs
for
all
scenarios
(
i.
e.,
dermal
MOEs
were
>
100),
except
for
the
following:

Agricultural
premises
and
equipment:

$
application
to
hard
surfaces:
low
pressure
handwand
(
MOE=
31),

$
application
to
hard
surfaces:
mopping
(
MOE=
70),
and
$
application
to
hard
surfaces:
foam
applicator
equipment
(
MOE=
8).
Page
33
of
49
Food
Handling,
Commercial/
Institutional,
and
Medical
Premises
and
Equipment:

$
application
to
hard
surfaces:
mopping
(
MOE=
66
commercial;
3
medical).

To
calculate
the
dermal
exposure
for
a
worker
treating
fruits
and
vegetables,
the
Consumer
Exposure
Pathway
of
the
Exposure
and
Fate
Assessment
Tool
(
CEM/
E­
FAST)
was
used.
CEM
calculates
conservative
estimates
of
inhalation
and
dermal
exposures
to
consumer
products.
The
estimated
dermal
MOE
for
the
fruit
and
vegetable
wash
is
2,300,
and
therefore,
not
of
concern.

Finally,
there
is
the
potential
for
exposure
to
machinists
contacting
chlorine
dioxide
when
used
as
a
material
preservative
in
metal
working
fluid
(
MWF).
There
is
a
potential
for
dermal
and
inhalation
exposure
when
a
worker
handles
treated
metalworking
fluids.
Because
of
the
high
vapor
pressure
of
chlorine
dioxide,
the
inhalation
route
of
exposure
is
not
assessed
in
the
typical
manner
(
i.
e.,
using
the
OSHA
PEL
for
oil
mist
x
percent
concentration
in
solution).
See
below
for
the
discussion
of
the
inhalation
route
of
exposure
for
occupational
workers.
The
dermal
route
of
exposure
to
machinists
occurs
after
the
chemical
has
been
incorporated
into
the
metalworking
fluid
and
a
machinist
is
using/
handling
this
treated
end­
product.
Short­,
intermediate­,
and
long­
term
exposure
estimates
were
derived
using
the
2­
hand
immersion
model
from
ChemSTEER.
The
results
indicate
that
the
short­,
intermediate­,
and
long­
term
dermal
MOE
is
14,000,
and
therefore,
not
of
concern.

Table
15.
Short­,
Intermediate­
Term
Risks
for
Occupational
Handlers
MOEc
Exposure
Scenario
Method
of
Application
Application
Rate
(
lb
ai/
gallon)
Quantity
Handled/
Treated
per
day
(
gallons)
Baseline
Dermala
(
Target
MOE>
100)
PPE
Gloves
Dermalb
(
Target
MOE>
100)

Agricultural
Premises
and
Equipment
Low
pressure
handwand
2
31
No
data
Liquid
Pour
0.188
1,300
6,300
Trigger­
pump
sprayer
0.015
0.26
240
570
Mopping
0.018
2
70
No
data
Application
to
hard
surfaces
Foam
applicator
equipment
0.025
60
3
8
Food
Handling,
Commercial/
Institutional,
and
Medical
Premises
and
Equipment
Mopping
0.019
2
66
No
data
Application
to
hard
surfaces
Trigger­
pump
sprayer
0.08
0.26
46
110
Page
34
of
49
Table
15.
Short­,
Intermediate­
Term
Risks
for
Occupational
Handlers
MOEc
Exposure
Scenario
Method
of
Application
Application
Rate
(
lb
ai/
gallon)
Quantity
Handled/
Treated
per
day
(
gallons)
Baseline
Dermala
(
Target
MOE>
100)
PPE
Gloves
Dermalb
(
Target
MOE>
100)

Human
Drinking
Water
Systems
Water
and
Storage
systems
Metering
pump
0.007
34,000
No
data
120
Material
Preservatives
MWF
Liquid
pour
0.0001
300
No
data
33,000
Industrial
Processes
and
Water
Systems
Paper
and
pulp
white
water
systems
Metering
pump
0.0344
lb
ai/
ton
paper
500
tons
paper
No
data
2,300
2.8
6,900
Oil
systems
Open
pour
0.069
5.6
NA
3,500
Swimming
Pools
and
Aquatic
Areas
Retention
ponds/
fountain
Liquid
pour
0.00001
10,000
No
data
670
Swimming
pools
(
public)
Solid
place
1.8E­
5
200,000
5
120
HVAC
Systems
Airless
sprayer
5
140
NA
HVAC
Fogger
(
liquid
pour)
0.007
0.25
2,000
NA
a
Baseline
Dermal:
Long­
sleeve
shirt,
long
pants,
no
gloves.
b
PPE
Dermal
with
gloves:
baseline
dermal
plus
chemical­
resistant
gloves.
c
MOE
=
NOAEL
(
mg/
kg/
day)
/
Daily
Dose
[
Where
short­
and
intermediate­
term
NOAEL
=
3
mg/
kg/
day
for
dermal
exposure].
Target
MOE
is
100
for
dermal
exposure.

7.2
Occupational
Post
Application
Exposure
7.2.1
Dermal
Post
Application
Exposure
No
information
is
available
to
assess
post
application/
bystander
dermal
exposure
to
uses
in
agricultural
premises
as
well
as
food
handling,
commercial/
institutional
and
medical
premises;
human
drinking
water
facilities;
industrial
processes;
and
retention
ponds.
However,
dermal
post
application
exposure
to
chlorine
dioxide
is
expected
to
be
less
than
that
of
the
dermal
contact
of
children
playing
on
treated
floor
surfaces.
Therefore,
the
dermal
exposure
route
is
not
believed
to
be
of
concern
in
these
industries.

7.2.2
Inhalation
Post
Application
Exposure
Page
35
of
49
Non­
Fogging
Uses
There
is
the
potential
for
the
off
gassing
of
chlorine
dioxide
during
some
applications
that
are
not
totally
enclosed
(
e.
g.,
spray
aqueous
solution,
mopping,
pouring,
etc).
Although
no
occupational
air
monitoring
data
have
been
submitted
to
assess
the
inhalation
route,
EPA
has
obtained
air
concentration
measurements
from
OSHA.
OSHA
maintains
a
data
base
known
as
the
Integrated
Management
Information
System
(
IMIS).
The
IMIS
entries
for
chlorine
dioxide
are
available
for
7
industry
Standard
Industrial
Classification
(
SIC)
codes.
Specific
uses
such
as
applicators,
bystanders
and
the
activities
involved
are
not
available.
The
SIC
codes
representing
the
chlorine
dioxide
data
in
IMIS
used
in
this
assessment
include:

 
SIC
0723
Crop
preparation
services
for
market;
 
SIC
1629
Heavy
construction;
 
SIC
2611
Pulp
mills;
 
SIC
2621
Paper
mills;
 
SIC
2819
Industrial
inorganic
chemicals;
 
SIC
2836
Biological
products;
and
 
SIC
3999
Manufacturing
industries.

The
data
selected
for
this
analysis
include
only
those
samples
that
are
reported
as
8­
hour
TWA
measurements
from
personal
air
samplers.
Other
samples,
such
as
peak
concentrations
and/
or
area
monitors,
have
been
omitted.
The
chlorine
dioxide
sampling
and
analytical
procedures
used
in
the
collection
of
the
data
in
IMIS
are
available
at
http://
www.
osha.
gov/
dts/
sltc/
methods/
inorganic/
id202/
id202.
html.
The
quantitative
LOD
from
this
method
is
0.004
ppm
for
a
4­
hour
sample
(
the
recommended
sampling
time).
The
reported
full
8­
hour
work
shift
samples
are
based
on
two
4­
hour
samples
collected
in
sequence.
The
inhalation
endpoint
selected
by
EPA
is
0.003
ppm,
just
below
the
OSHA
LOD
for
an
8­
hour
TWA
air
sample
[
i.
e.,
(
0.5
x
0.004
ppm
per
4
hrs)
+
(
0.5
x
0.004
ppm
per
4
hrs)=
0.004
ppm
per
8
hours].

The
summary
results
of
the
33
observations
taken
from
8­
hour
TWA
personal
air
samplers
for
chlorine
dioxide
are
above
the
EPA
selected
inhalation
reference
concentration
(
RfC)
of
0.003
ppm,
and
therefore,
are
of
concern.
Of
the
33
TWA
measurements
available,
21
of
those
measurements
were
below
the
LOD
of
0.004
ppm.
In
addition,
of
the
33
TWA
measurements,
only
3
were
at
or
above
the
OSHA
PEL
of
0.1
ppm.

Fogging
Uses
The
fogging
use
of
chlorine
dioxide
is
unique
such
that
no
persons
are
present
during
the
actual
application/
fogging.
There
is
also
a
greater
potential
for
chlorine
dioxide
gas
formation
from
fogging
then
an
aqueous­
based
application
such
as
mopping.
Therefore,
a
separate
assessment
was
developed
for
foggers
that
indicate
potential
inhalation
exposure
and
reentry
recommendations.
The
air
concentration
in
a
fogged
area
should
be
below
the
occupational
RfC
of
0.003
ppm
before
the
room
is
entered
by
persons
not
wearing
respiratory
protection.
EPA
Reg.
No.
74602­
2
was
used
to
illustrate
potential
air
concentrations.
Page
36
of
49
Concentrations
of
chlorine
dioxide
were
estimated
for
buildings
after
fogging
applications.
Air
concentrations
were
calculated
using
the
Multi­
Chamber
Concentration
and
Exposure
Model
(
MCCEM
v1.2).
MCCEM
estimates
average
and
peak
indoor
air
concentrations
of
chemicals
released
from
products
or
materials
in
houses,
apartments,
townhouses,
or
other
residences.
Although
the
data
libraries
contained
in
MCCEM
are
limited
to
residential
settings,
the
model
can
be
used
to
assess
other
indoor
environments.
MCCEM
has
the
capability
to
estimate
inhalation
exposures
to
chemicals,
calculated
as
single
day
doses,
chronic
average
daily
doses,
or
lifetime
average
daily
doses.

The
product,
EPA
Reg
#
74602­
2
(
sodium
chlorite
with
a
5%
chlorine
dioxide
equivalent)
has
a
maximum
application
rate
for
egg
houses
of
0.0083
lb
ai/
gal
(
1000
ppm
chlorine
dioxide
treatment
solution).
This
particular
product
specifically
lists
a
Dramm
fogger
for
the
application
(
i.
e.,
ultra
low
volume
(
ULV)).
According
to
the
registrant,
the
Dramm
fogger
for
chlorine
dioxide
applications
uses
2.5
ounces
of
the
diluted
product
per
225,000
cubic
feet
(
USEPA
2006),
and
the
label
states
to
run
the
fogger
for
five
minutes.
Note:
This
labeled
rate
should
be
added
to
all
chlorine
dioxide
fogger
uses.
If
other
registrants
require
a
higher
application
rate,
these
rates
need
to
be
brought
to
EPA's
attention
during
the
development
of
the
chlorine
dioxide
RED.

Using
an
air
exchange
rate
(
air
changes
per
hour
or
ACH)
of
0.18,
an
8­
hr
TWA
of
less
than
0.003
ppm
(
0.0084
mg/
m3)
is
expected
with
no
REI.
Although
there
appears
to
be
no
inhalation
risks
of
concern,
a
1­
hour
REI
would
be
prudent.

In
a
second
fogging
example,
EPA
Reg.
No.
21164­
3
allows
chlorine
dioxide
fogging
and
misting
applications
while
workers
are
in
the
room
if
the
level
of
chlorine
dioxide
does
not
exceed
the
TLV­
TWA
of
0.1
ppm.
The
use
directions
are
as
follows:

" 
may
be
added
to
the
plant
misting
or
fogging
systems
to
deodorize
and
to
control
odor
causing
bacteria,
mold
and
mildew
in
food
processing
plants,
dairies,
bottling
plants,
poultry,
meat
and
fish
plants
and
animal
facilities
such
as
poultry
houses,
swine
pens,
calf
barns
and
kennels.
If
the
TLV­
TWA
is
to
be
exceeded,
turn
off
air
handlers
and
vacate
people
and
livestock
from
the
rooms
to
be
fogged
or
misted.
Ventilate
for
15
minutes
prior
to
reentry.
Note
 
Be
careful
not
to
add
concentrated
acid
solutions
to
undiluted
DURA
KLOR
as
high
concentrations
of
chlorine
dioxide
gas
may
evolve.
The
concentration
of
chlorine
dioxide
in
the
diluted
DURA
KLOR
solution
should
not
be
allowed
to
exceed
0.5
ppm "

The
occupational
RfC
of
0.003
ppm
could
be
exceeded
based
on
these
use
directions
(
i.
e.,
workers
do
not
need
to
leave
treatment
area
unless
the
TLV­
TWA
of
0.1
ppm
is
exceeded).

EPA's
Risk­
based
RfC
versus
OSHA
PEL
It
is
also
important
to
note
that
the
OSHA
PEL
for
chlorine
dioxide
is
0.1
ppm.
Air
concentrations
above
the
PEL
are
assumed
to
be
mitigated
at
each
facility.
Facilities
using
chlorine
dioxide
are
not
required
to
mitigate
inhalation
exposures
until
the
air
concentration
reaches
0.1
ppm.
Based
on
the
occupational
inhalation
toxicological
endpoint
selected
for
chlorine
dioxide
(
i.
e.,
RfC
of
0.003
ppm),
levels
at
or
near
the
PEL
are
of
concern.
In
fact,
the
Page
37
of
49
capability
(
i.
e.,
LOD)
of
the
OSHA
sampling
method
is
insufficient
for
the
occupational
RfC
presented
in
this
document.
Reconciliation
of
the
EPA
risk­
based
RfC
and
the
current
OSHA
standards
will
be
made
during
the
regulatory
decision
phase
of
the
Reregistration
Eligibility
Decision
(
RED)
for
chlorine
dioxide.
The
various
cited
chlorine
dioxide
levels
from
other
organizations
are
reported
below
for
review
by
regulatory
managers.
Table
16.
Chlorine
Dioxide
Regulatory
and/
or
Recommended
Air
Concentrations
Organization
Time/
Duration
Description
Air
Concentration
(
ppm)
OSHA
8­
hour
TWA
PEL
0.1
8­
hour
TWA
TLV
0.1
ACGIH
15­
minutes
STEL
0.3
10­
hour
TWA
REL
0.1
NIOSH
30­
minutes
(
escape)
IDLH
5
8­
hour
TWA
RfC
­
Occupational
0.003
"
Short­
term"
RfC
 
Residential
for
single
exposures
0.05
EPA
Continuous
(
24/
7)
RfC
 
Residential
0.00007
8.0
INCIDENT
REPORT
ASSESSMENT
A
detailed
summary
of
the
human
incident
data
is
presented
in
the
document
"
Chlorine
Dioxide
Incident
Reports."
Below
is
a
brief
summary
of
this
information.
The
Agency
consulted
the
following
databases
for
poisoning
incident
data
for
chlorine
dioxide
and
other
similar
compounds:

(
1)
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,
with
enough
cases
and/
or
enough
documentation,
risk
mitigation
measures
may
be
suggested.
(
2)
Poison
Control
Centers
­
as
a
result
of
a
data
purchase
by
EPA,
OPP
received
Poison
Control
Center
data
covering
the
years
1993
through
2003
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.
(
3)
California
Department
of
Pesticide
Regulation
­
California
has
collected
uniform
data
on
suspected
pesticide
poisonings
since
1982.
Physicians
are
required,
by
statute,
to
report
to
their
local
health
officer
all
occurrences
of
illness
suspected
of
being
related
to
exposure
to
pesticides.
The
majority
of
the
incidents
involve
workers.
Information
on
exposure
(
worker
activity),
type
of
illness
(
systemic,
eye,
skin,
eye/
skin
and
respiratory),
likelihood
of
a
causal
relationship,
and
number
of
Page
38
of
49
days
off
work
and
in
the
hospital
are
provided.
(
4)
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.
(
5)
Published
Incident
Reports
­
Some
incident
reports
associated
with
chlorine
dioxide
related
human
health
hazards
are
published
in
the
scientific
literature.

There
are
some
reported
incidents
associated
with
exposure
to
end­
use
products
containing
chlorine
dioxide.
Inhalation
is
the
primary
route
of
exposure.
Most
of
the
incidents
are
related
to
irritation
reaction.
In
aqueous
media,
chlorine
and
chlorine
dioxide
dissolve
and
hydrolyze
to
produce
hypochlorous
acid
and
hypochlorite
ion,
which
react
in
swimming
pools
to
produce
breakdown
products
such
as
chloramines,
haloacetic
acid,
haloacetonitriles,
haloketones,
chloropicrin,
and
chloral
hydrate.
This
process
makes
it
difficult
to
separate
out
incidents
with
chlorine
dioxide
from
incidents
associated
with
chlorine,
chlorite
and
hypochlorite
ions.

The
most
common
symptoms
reported
for
cases
of
inhalation
exposure
were
respiratory
irritation/
burning,
irritation
to
mouth/
throat/
nose,
coughing/
choking,
shortness
of
breath,
dizziness,
flu­
like
symptoms,
and
headache.
Exposure
to
chlorinated
pool
water
has
also
been
reported
to
cause
red,
watery
eyes
as
well
as
dermal
effects,
such
as
generalized
rashes.

9.0
ECOTOXICOLOGY
ASSESSMENT
A
detailed
ecotoxicology
risk
assessment
for
chlorine
dioxide
is
provided
in
the
Environmental
Hazard
and
Risk
Assessment
Chapter.
The
summary
of
the
exposures
and
risks
are
presented
below.

Environmental
Modeling/
Exposure
The
Probabilistic
Distribution
Model
version
4
(
PDM4)
was
used
to
estimate
exposure
from
once­
through
cooling
tower
uses.
The
model
was
used
to
provide
the
percentage
of
days
per
year
various
concentrations
are
exceeded
for
several
different
flow,
application,
and
dosing
scenarios.
The
details
of
this
model
can
be
found
in
the
Environmental
Modeling
Chapter.

Three
different
flow
regimes
were
considered:
high
flow
[
power
plants
with
average
stream
flow
rates
of
1000
±
50
million
gallons
per
day
(
MGD)];
medium
flow
(
power
plants
with
average
stream
flow
rates
of
500
±
50
MGD);
and
low
flow
(
power
plants
with
average
stream
flow
rates
of
100
±
10
MGD).
Two
pesticide
application
scenarios,
continuous
feed
and
intermittent
feed,
were
used
in
the
modeling,
based
on
label
instructions.
For
continuous
feed
use,
the
label
rates
ranged
from
0.10
ppm
to
2.0
ppm
chlorine
dioxide/
sodium
chlorite
in
the
water.
For
intermittent
use,
the
label
rates
ranged
from
0.10
ppm
to
25
ppm
chlorine
dioxide/
sodium
chlorite
in
the
water.
A
single
label
contained
the
rate
of
800
ppm
chlorine
dioxide/
sodium
chlorite
and
did
not
specify
whether
this
was
for
continuous
or
intermittent
use.
It
is
believed
that
this
label
with
the
800
ppm
dose
rate
will
be
either
cancelled
or
amended
by
the
registrant
to
delete
this
dose.
The
concentrations
(
the
"
concentrations
of
concern,"
or
COC)
Page
39
of
49
used
in
the
model
were
endpoints
from
aquatic
organism
toxicity
studies
with
sodium
chlorite.

Exceedance
values
for
average
and
worst­
case
situations
were
modeled.
The
average
values
were
calculated
by
averaging
all
of
the
values
for
a
given
flow
category.
The
worst­
case
values
were
calculated
by
averaging
the
highest
(
peak)
values
for
a
given
flow
category.
Since
the
modeling
for
chlorine
dioxide/
sodium
chlorite
provides
results
as
percent
days
per
year
a
particular
concentration
is
exceeded,
Risk
Quotients
were
not
used
in
the
usual
way
to
provide
numeric
estimates
of
risk.
Instead,
the
endpoints
from
various
toxicity
studies
were
adjusted
to
determine
the
numeric
Level
of
Concern
(
LOC)
for
each
taxa
for
both
acute
and
chronic
effects.
The
adjustment
factor
is
the
same
as
the
one
used
with
the
RQ
method,
e.
g.
0.5
*
LC50
or
EC50
for
acute
effects,
and
0.05
*
LC50
or
EC50
for
acute
endangered
species
risks.
The
chronic
LOC
needs
no
adjustment.
The
modeling
results
provided
the
percentage
of
days
concentrations
were
exceeded
for
a
range
encompassing
the
numeric
LOCs.
When
a
specific
LOC
was
not
listed
in
the
modeling
output
tables,
the
percent
days
exceeded
for
the
LOC
was
interpolated
from
the
closest
numbers
above
and
below
the
specific
LOC.
The
percentage
of
days
was
then
multiplied
by
365
to
provide
the
number
of
days
per
year
the
LOC
is
exceeded.

For
terrestrial
organisms,
there
is
no
model
available
to
estimate
exposure
and
risk
from
discharge
of
once­
through
cooling
system
effluents
into
surface
waters.
The
rapid
degradation
of
the
chemicals,
coupled
with
the
generally
low
toxicity
of
chlorine
dioxide
and
sodium
chlorite
to
birds
and
mammals,
make
risk
to
these
organisms
unlikely.
The
very
limited
data
available
to
assess
the
phytotoxicity
of
chlorine
dioxide/
sodium
chlorite
make
it
difficult
to
determine
the
risk
to
terrestrial/
semi­
aquatic
plants.

For
aquatic
organisms,
acute
risk
is
anticipated
from
the
use
of
chlorine
dioxide/
sodium
chlorite
in
once­
through
cooling
towers
based
on
the
modeling
conducted.
At
the
highest
doses,
there
is
risk
to
freshwater
and
marine/
estuarine
fish
and
invertebrates
and
aquatic
plants,
and
at
the
lowest
doses
there
is
risk
only
to
freshwater
invertebrates.
Chronic
risk
to
aquatic
organisms
cannot
be
assessed
at
this
time
due
to
the
lack
of
chronic
toxicity
endpoints
for
fish
and
aquatic
invertebrates.
When
the
required
aquatic
chronic
toxicity
testing
described
above
is
submitted,
chronic
risk
to
these
organisms
will
be
assessed.

Ecological
Hazard
and
Risk
Studies
have
been
submitted,
which
fulfill
the
requirements
of
several
EPA
ecotoxicity
guidelines.
For
terrestrial
animals,
the
results
of
studies
to
examine
the
toxicity
of
chlorine
dioxide/
sodium
chlorite
to
birds
indicate
these
chemicals
range
from
slightly
to
highly
toxic
to
birds
on
an
acute
oral
basis
and
from
slightly
toxic
to
practically
non­
toxic
on
a
subacute
dietary
basis.
For
freshwater
aquatic
animals,
the
results
of
studies
examining
the
toxicity
of
chlorine
dioxide/
sodium
chlorite
to
freshwater
fish
indicate
these
chemicals
range
from
slightly
toxic
to
practically
non­
toxic
on
an
acute
basis.
For
aquatic
invertebrates,
the
studies
indicate
that
chlorine
dioxide
and
sodium
chlorite
range
from
very
highly
toxic
for
technical
grade
sodium
chlorite
a.
i.
to
practically
non­
toxic
for
the
formulated
product
on
an
acute
basis.
Results
of
toxicity
studies
indicate
that
chlorine
dioxide/
sodium
chlorite
are
slightly
toxic
to
estuarine/
marine
fish
on
an
acute
basis
and
range
from
highly
toxic
to
slightly
toxic
to
estuarine/
marine
invertebrates
on
an
acute
basis.
Page
40
of
49
For
terrestrial
plants,
results
of
toxicity
studies
indicate
that
chlorine
dioxide/
sodium
chlorite
are
moderately
toxic
to
terrestrial
plants.
However,
since
the
maximum
label
rate
for
many
of
the
chlorine
dioxide/
sodium
chlorite
once­
through
cooling
labels
was
not
used
in
these
tests,
it
is
necessary
to
conduct
Tier
II
testing
with
rice.
For
aquatic
plants,
toxicity
study
results
indicate
that
chlorine
dioxide/
sodium
chlorite
are
moderately
toxic
to
aquatic
plants.
The
oncethrough
cooling
tower
use
of
chlorine
dioxide/
sodium
chlorite
requires
that
5
aquatic
plant
tests
be
conducted
due
to
the
algaecidal
nature
of
the
chemical
and
the
likelihood
of
exposure
to
aquatic
plants
in
surface
waters
receiving
industrial
facility
outfall
from
the
cooling
system;
however,
only
one
study
(
1
species)
under
this
topic
has
been
submitted
and
5
are
required.
The
following
aquatic
plant
studies
are
still
required:
blue­
green
cyanobacteria
(
Anabaena
flosaquae
freshwater
diatom
(
Navicula
pelliculosa),
marine
diatom
(
Skeletonema
costatum)
and
floating
macrophyte
(
Lemna
gibba).

Data
is
still
required
for
the
following
guideline
requirements:
(
1)
a
freshwater
fish
early
life­
stage
test
using
the
technical
grade
of
the
active
ingredient,
(
2)
a
freshwater
aquatic
invertebrate
life­
cycle
test
using
the
technical
grade
of
the
active
ingredient,
(
3)
an
estuarine/
marine
invertebrate
life­
cycle
toxicity
test
is
required
due
to
the
high
acute
toxicity
of
sodium
chlorite
to
estuarine/
marine
invertebrates;
however,
freshwater
invertebrates
tend
to
be
more
sensitive
than
estuarine/
marine
invertebrates
to
sodium
chlorite
on
an
acute
basis,
and,
therefore,
freshwater
life­
cycle
endpoints
will
suffice
for
assessing
risk
to
estuarine/
marine
invertebrate
species.

Table
17.
Acute
Oral
Toxicity
of
Chlorine
Dioxide
and
Sodium
Chlorite
to
Birds
Substance/%
Active
Ingredient
(
AI)
Organism
Endpoints/
Results
(
mg/
kg)
(
95%
conf.
interval)
Reference
Study
Classification
Sodium
Chlorite/
80%
Northern
bobwhite
(
Colinus
virginianus)
LD50
=
382
(
300­
520)
NOEL
=
175
Robaidek,
1985
ACC
#
259373
acceptable
Sodium
Chlorite/
80%
Northern
bobwhite
(
Colinus
virginianus)
LD50
=
390
(
310­
490)
NOEL
=
N.
R.
Robaidek
and
Johnson,
1985
ACC
#
257341
acceptable
Sodium
Chlorite/
80%
Northern
bobwhite
(
Colinus
virginianus)
LD50
=
395
(
272­
573)
NOEL
=
N.
R.
Fletcher,
1984
ACC
#
253378
acceptable
Sodium
Chlorite/
83%
Northern
bobwhite
(
Colinus
virginianus)
LD50
=
660
(
540­
810)
Fletcher,
1973
MRID
#
31610
acceptable
Sodium
Chlorite/
80%
Northern
bobwhite
(
Colinus
virginianus)
LD50
=
467
(
372­
585)
Beavers,
1984
ACC
#
254177
acceptable
Sodium
Chlorite/
80%
Mallard
Duck
(
Anas
platyrhynchos)
LD50
>
31.25
Beavers,
1984
ACC
#
254176
supplemental
Sodium
Chlorite/
25%
Northern
bobwhite
(
Colinus
virginianus
LD50
=
797(
420­
2594)
NOEL=
125
MBA
Laboratories,
1984
ACC#
252854
acceptable
Page
41
of
49
Table
18.
Acute
Ecotoxicity
of
Chlorine
Dioxide
and
Sodium
Chlorite
Substance/%
Active
Ingredient
(
AI)
Organism
Endpoints/
Results
(
ppm)
(
95%
conf.
interval)
Reference
Study
Classificatio
n
Freshwater
fish
Sodium
Chlorite/
80%
Rainbow
trout
(
Oncorhynchus
mykiss)
LC50
=
360
(
216­
600)
NOEC
=
216
Barrows,
1984
MRID
#
94068007
acceptable
Sodium
Chlorite/
80%
Bluegill
(
Lepomis
macrochirus)
LC50
=
244
(
196­
304)
NOEC
=
108
Larkin,
1984
ACC
#
254181
acceptable
Sodium
Chlorite/
80%
Rainbow
trout
(
Oncorhynchus
mykiss)
LC50
=
360
(
216­
600)
NOEC
=
216
Larkin,
1984
ACC
#
254180
acceptable
Sodium
Chlorite/
80.25%
Bluegill
(
Lepomis
macrochirus)
LC50
=
265
(
231­
309)
NOEC
=
130
EG&
G,
Bionomics,
1978
ACC
#
69809
supplemental
Sodium
Chlorite/
79%
Bluegill
(
Lepomis
macrochirus)
LC
50
=
208
(
165­
262)
NOEC
=
N.
R.
Sleight
III,
1971
MRID
#
131351
supplemental
Sodium
Chlorite/
79%
Rainbow
trout
(
Oncorhynchus
mykiss)
LC50
=
50.6
(
38­
65.8)
NOEC
=
32
Sleight
III,
1971
MRID
#
131351
supplemental
Sodium
Chlorite/
80%
Rainbow
trout
(
Oncorhynchus
mykiss)
LC50
>
100
NOEC
=
N.
R.
McMillen,
1984
ACC
#
253743
supplemental
Sodium
Chlorite/
80%
Bluegill
(
Lepomis
macrochirus)
LC50
>
100
NOEC
=
N.
R.
McMillen,
1984
ACC
#
253743
supplemental
Sodium
Chlorite/
25%
Rainbow
trout
(
Oncorhynchus
mykiss)
LC50
=
203
(
175­
236)
NOEC
=
100
MBA
Laboratories,
1984
ACC
#
252854
acceptable
Sodium
Chlorite/
25%
Bluegill
(
Lepomis
macrochirus)
LC50
=
222
(
207­
237)
NOEC
=
186
MBA
Laboratories,
1983
ACC
#
252854
supplemental
Sodium
Chlorite/
81.5%
Bluegill
(
Lepomis
macrochirus)
LC50
=
310
(
270­
350)
NOEC
=
220
Sousa,
1981
ACC
#
245697
acceptable
Sodium
Chlorite/
80.25%
Rainbow
trout
(
Oncorhynchus
mykiss)
LC50
=
290
(
250­
340)
NOEC
=
70
EG&
G,
Bionomics,
1979
ACC
#
69810
acceptable
Sodium
Chlorite/
80%
Rainbow
trout
(
Oncorhynchus
mykiss)
LC50
=
340
(
220­
600)
NOEC
=
N.
R.
Sousa
and
Surprenant,
1984
ACC
#
253379
acceptable
Sodium
Chlorite/
80%
Bluegill
(
Lepomis
macrochirus)
LC50
=
420
(
220­
600)
NOEC
=
N.
R.
Sousa
and
Surprenant,
1984
MRID
#
94068006
acceptable
Page
42
of
49
Table
18.
Acute
Ecotoxicity
of
Chlorine
Dioxide
and
Sodium
Chlorite
Substance/%
Active
Ingredient
(
AI)
Organism
Endpoints/
Results
(
ppm)
(
95%
conf.
interval)
Reference
Study
Classificatio
n
Freshwater
Invertebrates
Sodium
Chlorite/
80%
Daphnia
magna
EC50
=
0.027
(
0.021­
0.031)
NOEC
=
0.003
Barrows,
1984
MRID
#
146162
acceptable
Sodium
Chlorite/
80%
Daphnia
magna
EC50
=
0.39
(
0.32­
0.54)
NOEC
=
N.
R.
Hoberg
and
Surprenant,
1984
MRID
#
141149
acceptable
Sodium
Chlorite/
79%
Daphnia
magna
LC50
=
0.29
(
0.25­
0.33)
NOEC
=
0.10
Vilkas,
1976
MRID
#
131350
acceptable
Sodium
Chlorite/
80%
Daphnia
magna
LC50
=
0.08
(
0.06­
0.10)
NOEC
=
0.06
Larkin,
1984
ACC
#
254182
acceptable
Sodium
Chlorite/
80%
Daphnia
magna
LC50
=
0.146
(
0.12
­
0.18)
NOEC
=
0.06
Nachrord,
1984
MRID
#
94068009
acceptable
Sodium
Chlorite/
25%
Daphnia
magna
LC50
=
1.4
(
1.0­
1.9
)
NOEC
=
0.4
MBA
Laboratories,
1984
ACC
#
252854
supplemental
Estuarine/
Marine
Fish
Sodium
Chlorite/
79%
Sheepshead
minnow
(
Cyprinodon
variegatus)
LC50
=
75
(
62.6­
89.8)
NOAEC
=
13.9
Yurk
and
Overman,
1994
MRID
#
43259401
acceptable
Estuarine/
Marine
Invertebrates
Sodium
Chlorite/
79%
Eastern
oyster
(
Crassostrea
virginica)
96
hour
LC50/
EC50
=
21.4
(
14.3­
27.1)
NOEC
=
14.3
Yurk
and
Overman,
1994
MRID
#
43259403
acceptable
Sodium
Chlorite/
79%
Mysid
(
Mysidopsis
bahia)
96
hour
LC50/
EC50
=
0.576
(
0.44­
0.75)
NOEC=
N.
R.
Yurk
and
Overman,
1994
MRID
#
43259402
acceptable
Terrestrial/
Semi­
aquatic
Plants
Sodium
Chlorite/
80%
Monocots
&
Dicots
(
10
Species)
EC25
=
>
3.5
Backus
et
al.,
1990
MRID
#
41843101
acceptable
Sodium
Chlorite/
80%
Monocots
&
Dicots
(
10
Species)
EC25
=
>
3.5
Backus
et
al.,
1990
MRID
#
41843102
acceptable
Sodium
Chlorite/
80%
Buckwheat
(
Polygonum
convolvulus)
EC25
=
<
3.5
Backus
et
al.,
1990
MRID
#
41843102
acceptable
Aquatic
Plants
Sodium
Chlorite/
80%
Green
Algae
(
Selenastrum
capricornutum)
EC50
=
1.32
(
1.18­
1.47)
NOEC
=
<
0.62
Ward
and
Boeri,
1991
MRID
#
41880403
supplemental
Page
43
of
49
Table
19.
Avian
Subacute
Dietary
Toxicity
of
Chlorine
Dioxide
and
Sodium
Chlorite
Substance/%
AI
Organism
LC50
(
ppm)
(
95
%
c.
i.)
NOAEC
(
ppm)
Reference
Study
Classification
Sodium
Chlorite/
80%
Mallard
Duck
(
Anas
platyrhynchos)
>
5000
5000
Johnson,
1984
MRID
#
94068008
acceptable
Sodium
Chlorite/
80%
Northern
bobwhite
(
Colinus
virginianus)
>
5000
N.
R.
Fletcher,
1984
ACC
#
253378
acceptable
Sodium
Chlorite/
80%
Mallard
Duck
(
Anas
platyrhynchos)
>
5000
N.
R.
Fletcher,
1984
ACC
#
253378
acceptable
Sodium
Chlorite/
80%
Northern
bobwhite
(
Colinus
virginianus)
>
5000
N.
R.
Johnson,
1984
MRID
#
94068005
acceptable
Sodium
Chlorite/
80%
Mallard
Duck
(
Anas
platyrhynchos)
>
5620
N.
R.
Beavers,
1984
ACC
#
254178
acceptable
Sodium
Chlorite/
80%
Northern
bobwhite
(
Colinus
virginianus)
>
5620
N.
R.
Beavers,
1984
ACC
#
254179
acceptable
Sodium
Chlorite/
80%
Northern
bobwhite
(
Colinus
virginianus)
>
10,000
N.
R.
Fink,
1977
MRID
#
130649
acceptable
Sodium
Chlorite/
80%
Mallard
Duck
(
Anas
platyrhynchos)
>
10,000
N.
R.
Fink,
1977
MRID
#
130650
acceptable
Sodium
Chlorite/
25%
Mallard
Duck
(
Anas
platyrhynchos)
18686
(
8186­
109184)
1250
MBA
Laboratories,
1983
ACC
#
252854
acceptable
Sodium
Chlorite/
25%
Northern
bobwhite
(
Colinus
virginianus)
2031(
1226­
3903)
417
MBA
Laboratories,
1984
ACC
#
252854
acceptable
Listed
Species
Consideration
Section
7
of
the
Endangered
Species
Act,
16
U.
S.
C.
Section
1536(
a)(
2),
requires
all
federal
agencies
to
consult
with
the
National
Marine
Fisheries
Service
(
NMFS)
for
marine
and
anadromous
listed
species,
or
the
United
States
Fish
and
Wildlife
Services
(
FWS)
for
listed
wildlife
and
freshwater
organisms,
if
they
are
proposing
an
"
action"
that
may
affect
listed
species
or
their
designated
habitat.
Each
federal
agency
is
required
under
the
Act
to
insure
that
any
action
they
authorize,
fund,
or
carry
out
is
not
likely
to
jeopardize
the
continued
existence
of
a
listed
species
or
result
in
the
destruction
or
adverse
modification
of
designated
critical
habitat.
To
jeopardize
the
continued
existence
of
a
listed
species
means
"
to
engage
in
an
action
that
Page
44
of
49
reasonably
would
be
expected,
directly
or
indirectly,
to
reduce
appreciably
the
likelihood
of
both
the
survival
and
recovery
of
a
listed
species
in
the
wild
by
reducing
the
reproduction,
numbers,
or
distribution
of
the
species."
50
C.
F.
R.
§
402.02.

To
facilitate
compliance
with
the
requirements
of
the
Endangered
Species
Act
subsection
(
a)(
2)
the
Environmental
Protection
Agency,
Office
of
Pesticide
Programs
has
established
procedures
to
evaluate
whether
a
proposed
registration
action
may
directly
or
indirectly
reduce
appreciably
the
likelihood
of
both
the
survival
and
recovery
of
a
listed
species
in
the
wild
by
reducing
the
reproduction,
numbers,
or
distribution
of
any
listed
species
(
U.
S.
EPA,
2004).
After
the
Agency's
screening­
level
risk
assessment
is
performed,
if
any
of
the
Agency's
Listed
Species
LOC
Criteria
are
exceeded
for
either
direct
or
indirect
effects,
a
determination
is
made
to
identify
if
any
listed
or
candidate
species
may
co­
occur
in
the
area
of
the
proposed
pesticide
use.
If
determined
that
listed
or
candidate
species
may
be
present
in
the
proposed
use
areas,
further
biological
assessment
is
undertaken.
The
extent
to
which
listed
species
may
be
at
risk
then
determines
the
need
for
the
development
of
a
more
comprehensive
consultation
package
as
required
by
the
Endangered
Species
Act.

Acute
risk
to
listed
birds
and
mammals
is
not
anticipated
from
the
use
of
chlorine
dioxide
and
sodium
chlorite
products
due
to
low
exposure
and
low
toxicity.
Further
discussion
is
needed
before
it
can
be
determined
if
there
are
risks
to
listed
aquatic
organisms
from
the
once
through
cooling
tower
use
of
chlorine
dioxide/
sodium
chlorite.

Chronic
risks
to
listed
aquatic
organisms
cannot
be
assessed
at
this
time;
this
risk
will
be
assessed
when
required
chronic
toxicity
data
are
submitted
to
and
evaluated
by
the
Agency.

10.0
REFERENCES
Abdel­
Rahman,
et
al.
(
1984):
The
kinetics
of
chlorite
and
chlorate
in
the
rat.
J
Am
Coll
Toxicol
3:
261­
267.

ACC
245697.
Sousa,
J.
V.
1981.
Acute
Toxicity
of
Sodium
Chlorite
to
Bluegill
(
Lepomis
macrochirus).
Unpublished
Data.
Conducted
by
EG&
G,
Bionomics
for
Olin
Chemicals.

ACC
252854.
1984.
96­
Hour
LC50
in
Juvenile
Rainbow
Trout.
Unpublished
Data.
Conducted
by
Microbiological
and
Biochemical
Assay
Laboratories
for
Magna
Corporation.

ACC
252854.
1983.
96­
Hour
LC50
in
Bluegill
Perch.
Unpublished
Data.
Conducted
by
Microbiological
and
Biochemical
Assay
Laboratories
for
Magna
Corporation.

ACC
252854.
1984.
48­
Hour
LC50
in
Daphnia
magna.
Unpublished
Data.
Conducted
by
Microbiological
and
Biochemical
Assay
Laboratories
for
Magna
Corporation.

ACC
252854.
1984.
Avian
Dietary
LC50
in
Bob
White
Quail.
Unpublished
Data.
Conducted
by
Microbiological
and
Biochemical
Assay
Laboratories
for
Magna
Corporation.

ACC
252854.
1983.
Avian
Dietary
LC50
in
Mallard
Ducks.
Unpublished
Data.
Conducted
by
Page
45
of
49
Microbiological
and
Biochemical
Assay
Laboratories
for
Magna
Corporation.

ACC
252854.
1984.
Avian
Single­
Dose
Oral
LD50
in
Bobwhite
Quail.
Unpublished
Data.
Conducted
by
Microbiological
and
Biochemical
Assay
Laboratories
for
Magna
Corporation.

ACC
253378.
Fletcher,
D.
1984.
8­
Day
Dietary
LC50
Study
with
Sodium
Chlorite
in
Mallard
Ducklings.
Unpublished
Data.
Conducted
by
Bio­
Life
Associates,
Ltd.
for
Calgon
Corporation.

ACC
253378.
Fletcher,
D.
1984.
8­
Day
Dietary
LC50
Study
with
Sodium
Chlorite
in
Bobwhite
Quail.
Unpublished
Data.
Conducted
by
Bio­
Life
Associates,
Ltd.
for
Calgon
Corporation.

ACC
253378.
Fletcher,
D.
1984.
Acute
Oral
Toxicity
Study
with
Sodium
Chlorite
in
Bobwhite
Quail.
Unpublished
Data.
Conducted
by
Bio­
Life
Associates,
Ltd.
for
Calgon
Corporation.

ACC
253379.
Sousa,
J.
V.
and
D.
C.
Surprenant.
1984.
Acute
Toxicity
of
AC­
66
to
Rainbow
Trout
(
Salmo
gairdneri).
Unpublished
Data.
Conducted
by
Springborn
Bionomics,
Inc.
for
Calgon
Corporation.

ACC
253743.
McMillen,
C.
1984.
Static
Bioassay
on
Sodium
Chlorite
to
Rainbow
Trout
and
Bluegill
Sunfish.
Unpublished
Data.
Conducted
by
Environmental
Research
Group,
Inc.
for
Rio
Linda
Chemical
Company,
Inc.

ACC
254176.
Beavers,
1984.
An
Acute
Oral
Toxicity
Study
in
the
Mallard
with
Sodium
Chlorite.
Unpublished
Data.
Conducted
by
Wildlife
International,
Ltd.
for
TR
America
Chemicals,
Inc.

ACC
254177.
Beavers,
1984.
An
Acute
Oral
Toxicity
Study
in
the
Bobwhite
with
Sodium
Chlorite.
Unpublished
Data.
Conducted
by
Wildlife
International,
Ltd.
for
TR
America
Chemicals,
Inc.

ACC
254178.
Beavers,
1984.
A
Dietary
LC50
Study
in
the
Mallard
Duck
with
Sodium
Chlorite.
Unpublished
Data.
Conducted
by
Wildlife
International,
Ltd.
for
TR
America
Chemicals,
Inc.

ACC
254179.
Beavers,
1984.
A
Dietary
LC50
Study
in
the
Bobwhite
with
Sodium
Chlorite.
Unpublished
Data.
Conducted
by
Wildlife
International,
Ltd.
for
TR
America
Chemicals,
Inc.

ACC
254180.
Larkin,
J.
1984.
The
Acute
Toxicity
of
Sodium
Chlorite
to
Rainbow
Trout
(
Salmo
gairdneri).
Unpublished
Data.
Conducted
by
Biospherics
Incorporated
for
TR
America
Chemicals,
Inc.

ACC
254181.
Larkin,
J.
1984.
The
Acute
Toxicity
of
Sodium
Chlorite
to
Bluegill
Sunfish
(
Lepomis
macrochirus).
Unpublished
Data.
Conducted
by
Biospherics
Incorporated
for
TR
America
Chemicals,
Inc.
Page
46
of
49
ACC
254182.
Larkin,
J.
1984.
Acute
Toxicity
of
Sodium
Chlorite
to
Daphnia
magna
Strauss.
Unpublished
Data.
Conducted
by
Biospherics
Incorporated
for
TR
America
Chemicals,
Inc.

ACC
257341.
Robaidek
and
Johnson,
1985.
Avian
Single­
dose
Oral
LD50:
Bob
White
Quail
(
Colinus
virginianus).
Unpublished
Data.
Conducted
by
Hazleton
Laboratories
America,
Inc.
for
Rio
Linda
Chemical
Company.
ACC
259373.
Robaidek,
E.
1985.
Avian
Single­
Dose
Oral
LD50
Bobwhite
Quail.
Unpublished
Data.
Conducted
by
Hazleton
Laboratories
America,
Inc.
for
Degussa
Corporation.

ACC
265867.
1994.
Mutagenicity
Evaluation
of
Chlorine
Dioxide
in
the
Mouse
Lymphoma
Foreword
Mutation
Assay.
Litton
Bionetics,
Kensington,
MD,
LBI
Project
No.
20989,
March
1984.

BCI
(
2002).
(
Need
to
get
full
citation
for
the
HVAC
air
monitoring
study.)

CMA
(
1996):
Sodium
Chlorite:
Drinking
Water
Rat
Two­
Generation
Reproductive
Toxicity
Study.
Chemical
Manufacturers
Association.
Quintiles
Report
Ref.
CMA/
17/
96.
MRID
4535809.
Gill,
M.
T.
et.
al.(
2000),
Two­
generation
Reproduction
and
Developmental
Neurotoxicity
Study
with
Sodium
Chlorite
in
the
Rat.
J.
Appl.
Toxicol.
20,
291­
303.

Dalhamn,
T.
(
1957):
Chlorine
Dioxide:
Toxicity
in
Animal
Experiments
and
Industrial
Risks.
Arch.
Ind.
Health
15:
101­
107.

Daniel,
F.
B.,
et
al.
(
1990):
Comparative
subchronic
toxicity
studies
of
three
disinfectants.
J
Am
Water
Works
Assoc
82:
61­
69.

FDA.
1994.
Memo:
FAP:
4A4433,
1994).
FDA
extensively
reviewed
the
efficacy
and
the
analytical
chemistry
data
on
the
residues
 
full
reference
not
found
in
documents
Haag,
H.
B.
(
1949):
The
effect
on
rats
of
chronic
administration
of
sodium
chlorite
and
chlorine
dioxide
in
the
drinking
water.
Report
to
the
Mathieson
Alkali
Works
from
H.
B.
Haag
of
the
Medical
College
of
Virginia.
February
7,
1949.

Harrington,
R.
M.,
et
al.
(
1995):
Subchronic
toxicity
of
sodium
chlorite
in
the
rat.
J
Am
Coll
Toxicol
14:
21­
33.
42301601
Ridgway,
P.(
1992)
13
Week
Oral(
Gavage)
Toxicity
Study
in
the
Rat:
Lab
Project
Number:
CMA/
13/
R:
CD­
6.0­
Tox.
Unpublished
study
prepared
by
Toxicol
Labs
Ltd
for
the
CMA/
Chlorine
Dioxide
Panel.
329p.

Kurokawa,
Y.,
et
al.
(
1984):
Studies
on
the
promoting
and
complete
carcinogenic
activities
of
some
oxidizing
chemicals
in
skin
carcinogenesis.
Cancer
Lett
24:
299­
304.

Meier,
J.
R.,
et
al.
(
1985):
Evaluation
of
chemicals
used
for
drinking
water
disinfection
for
production
of
chromosomal
damage
and
sperm­
head
abnormalities
in
mice.
Environ
Mutagen
7:
201­
211.
Page
47
of
49
Miller,
R.
G.,
et
al.
(
1986):
Results
of
toxicological
testing
of
Jefferson
Parish
pilot
plant
samples.
Environ
Health
Perspect
69:
129­
139.

MRID
31610.
Fletcher,
D.
1973.
Acute
Oral
Toxicity
Study
with
Sodium
Chlorite
in
Bobwhite
Quail.
Unpublished
Data.
Conducted
by
Industrial
BIO­
TEST
Laboratories,
Inc.
for
Olin
Corporation.

MRID
69809.
1978.
Acute
Toxicity
of
Sodium
Chlorite
to
Bluegill
(
Lepomis
macrochirus).
Unpublished
Data.
Conducted
by
EG&
G,
Bionomics,
Aquatic
Toxicology
Laboratory
for
Olin
Chemicals.

MRID
69810.
1979.
Acute
Toxicity
of
Sodium
Chlorite
to
Rainbow
Trout
(
Salmo
gairdneri).
Unpublished
Data.
Conducted
by
EG&
G,
Bionomics,
Aquatic
Toxicology
Laboratory
for
Olin
Chemicals.

MRID
130649.
Fink,
R.
1977.
Eight­
day
Dietary
LC50
­
Bobwhite
Quail
 
Sodium
Chlorite.
Unpublished
Data.
Conducted
by
Wildlife
International,
Ltd.
for
Olin
Corporation.

MRID
130650.
Fink,
R.
1977.
Eight­
day
Dietary
LC50
 
Mallard
Duck
 
Sodium
Chlorite.
Unpublished
Data.
Conducted
by
Wildlife
International,
Ltd.
for
Olin
Corporation.

MRID
131350.
Vilkas,
A.
G.
1976.
Acute
Toxicity
of
Textone
to
the
Water
Flea
Daphnia
magna
Strauss.
Unpublished
Data.
Conducted
by
Aquatic
Environmental
Sciences
for
Olin
Corporation.

MRID
131351.
Sleight
III,
B.
H.
1971.
Acute
Toxicity
of
Sodium
Chlorite
to
Bluegill
(
Lepomis
macrochirus)
and
Rainbow
Trout
(
Salmo
gairdneri).
Unpublished
Data.
Conducted
by
Bionomics,
Inc.

MRID
141149.
Hoberg,
J.
R.
and
D.
C.
Surprenant.
1984.
Acute
Toxicity
of
AC­
66
to
Daphnids
(
Daphnia
magna).
Unpublished
Data.
Conducted
by
Springborn
Bionomics,
Inc.
for
Calgon
Corporation.

MRID
146162.
Barrows,
1984.
The
Acute
Toxicity
of
Sodium
Chlorite
Technical
to
the
Water
Flea,
Daphnia
magna
in
a
Static
Test
System.
Unpublished
Data.
Conducted
by
Biospherics
Incorporated
for
Degussa
Corporation.

MRID
40168704.
1985.
Acute
Dermal
LD50
on
Rabbit
 
Sodium
Chlorite
Powder,
Lot
#
110984­
15.
Gibraltar
Biological
Lab,
Inc.
(
Fairfield,
NJ),
Internaltional
Dioxcide,
Inc.
Study
Number
GBL
024065,
April
23,
1985.

MRID
41843101.
Backus,
P.,
K.
E.
Crosby
and
L.
J.
Powers.
1990.
Effect
of
Sodium
Chlorite
on
Vegetative
Vigor
of
Plants
(
Tier
I).
Unpublished
Data.
Conducted
by
Ricerca,
Inc.
for
the
Sodium
Chlorite
Reregistration
Task
Force.
Page
48
of
49
MRID
41843102.
Backus,
P.,
K.
E.
Crosby
and
L.
J.
Powers.
1990.
Effect
of
Sodium
Chlorite
on
Seed
Germination/
Seedling
Emergence
(
Tier
I).
Unpublished
Data.
Conducted
by
Ricerca,
Inc.
for
the
Sodium
Chlorite
Reregistration
Task
Force.

MRID
41880403.
Ward,
T.
J.
and
R.
L.
Boeri.
1991.
Static
Acute
Toxicity
of
Sodium
Chlorite
to
the
Freshwater
Alga,
Selenastrum
capricornutum.
Unpublished
Data.
Conducted
by
EnviroSystems
Division,
Resource
Analysis,
Inc.
for
the
Sodium
Chlorite
Reregistration
Task
Force.

MRID
42587501.
Popendorf,
W.;
Selim,
M.;
Kross,
B.
1992.
Chemical
Manufacturers
Association
Antimicrobial
Exposure
Assessment
Study:
Second
Replacement
to
MRID
41761201:
Lab
Project
Number:
Q626.
Unpublished
study
prepared
by
The
University
of
Iowa.
MRID
43259401.
Yurk,
J.
J.
and
M.
A.
Overman.
1994.
Acute
Toxicity
of
Sodium
Chlorite
to
the
Sheepshead
Minnow
(
Cyprinodon
variegatus).
Conducted
by
Environmental
Science
&
Engineering,
Inc.
for
the
Chemical
Manufacturers
Association.

MRID
43259402.
Yurk,
J.
J.
and
M.
A.
Overman.
1994.
Acute
Toxicity
of
Sodium
Chlorite
to
Mysid
Shrimp.
Conducted
by
Environmental
Science
&
Engineering,
Inc.
for
the
Chemical
Manufacturers
Association.

MRID
43259403.
Yurk,
J.
J.
and
M.
A.
Overman.
1994.
Effect
of
Sodium
Chlorite
on
New
Shell
Growth
in
Eastern
Oyster
(
Crassostrea
virginica).
Conducted
by
Environmental
Science
&
Engineering,
Inc.
for
the
Chemical
Manufacturers
Association.

MRID
94068005.
Johnson,
G.
1984.
Avian
Dietary
LC50
Bobwhite
Quail
(
Colinus
virginianus).
Unpublished
Data.
Conducted
by
Hazleton
Laboratories
America,
Inc.
for
Degussa
Corporation.

MRID
94068006.
Sousa
and
Surprenant,
1984.
Acute
Toxicity
of
A­
66
(
Technical
Sodium
Chlorite)
to
Bluegill
(
Lepomis
macrochirus).
Unpublished
Data.
Conducted
by
Springborn
Binomics,
Inc
for
Calgon
Corporation.

MRID
94068007.
Barrows,
B.
1984.
The
Acute
Toxicity
of
Sodium
Chlorite
Technical
to
the
Rainbow
Trout,
Salmo
gairdneri,
in
a
Static
Test
System.
Unpublished
Data.
Conducted
by
Biospherics
Incorporated
for
Degussa
Corporation.

MRID
94068008.
Johnson,
G.
1984.
Avian
Dietary
LC50
Mallard
Duck
(
Anas
platyrhynchos).
Unpublished
Data.
Conducted
by
Hazleton
Laboratories
America,
Inc.
for
Degussa
Corporation.

MRID
94068009.
Nachrord,
S.
1984.
Daphnia
LC50
Bioassay.
Unpublished
Data.
Conducted
by
Anater
Tesconi
Circle
for
Rio
Linda
Chemical
Company,
Inc.

MRID
41715701.
Irvine,
Lorraine
F.
Sodium
Chlorite:
Rabbit
Teratology
Study
(
Drinking
Water
Administration).
Toxicol.
Labs,
Ltd.,
Ledbury,
UK,
Study
Number
CMA/
3/
R,
September
21,
1990.
Page
49
of
49
MRID
42484101.
Acute
Inhalation
Toxicity
Evaluation
in
Rats.
International
Research
and
Development
Corporation
(
IRDC),
Mattawan,
MI.
Lab.
Project
No.
632­
001,
August
14,
1992.

MRID
43441903.
Primary
Eye
Irritation
Study
in
Rabbits.
Stillmeadow,
Inc.,
Sugar
Land,
TX,
Lab.
Project
No.
1441­
94,
October
11,
1994.

MRID
43558601.
Abdel­
Rahman,
et
al.,
"
Toxicity
of
Alcide,"
published
in
J.
Appl.
Toxicol.
2(
3):
160­
164,
1982.

Orme,
J.,
et
al.
(
1985):
Effects
of
chlorine
dioxide
on
thyroid
function
in
neonatal
rats.
J
Toxicol
Environ
Health
15:
315­
322.

Paulet
G
and
S.
Desbrousses
(
1970):
On
the
action
of
ClO2
at
low
concentrations
on
laboratory
animals.
Arch
Mal
Prof
31:
97­
106.

Paulet
G
and
S.
Desbrousses
(
1972):
On
the
toxicology
of
chlorine
dioxide.
Arch
Mal
Prof
33:
59­
61.

Paulet
G
and
S.
Desbrousses
(
1974):
Action
of
a
discontinuous
exposure
to
chlorine
dioxide
(
ClO2)
on
the
rat.
Arch
Mal
Prof
35:
797­
804.

PHED
Surrogate
Exposure
Guide.
1998.
Estimates
of
Worker
Exposure
from
the
Pesticide
Handler
Exposure
Database
Version
1.1.
August,
1998.

Robinson,
M;
Bull,
RJ;
Schmaer,
M;
Long,
RF.
(
1986)
Epidermal
hyperplasia
in
the
mouse
skin
following
treatment
with
alternate
drinking
water
disinfectants.
Environ
Health
Perspect
69:
293­
300.

USEPA.
2004.
Overview
of
the
Ecological
Risk
Assessment
Process
in
the
Office
of
Pesticide
Programs
U.
S.
Environmental
Protection
Agency
­
Endangered
and
Threatened
Species
Effects
Determinations,
1/
23/
04.

USEPA.
2000a.
Toxicological
Review
of
Chlorine
Dioxide
and
Chlorite,
Integrated
Risk
information
System
(
IRIS).

USEPA.
2000b.
Residential
SOPs.
EPA
Office
of
Pesticide
Programs 
Human
Health
Division.
Dated
April
5,
2000.

USEPA.
1998.
AD
Memo
by
Tim
McMahon
and
A.
Najm
Shamim
to
Norm
Cook,
March,
1998.