Document ID: EPA-HQ-OPP-2004-0303-0003
Agency: epa
Document Type: Supporting & Related Material
Title: 
Posted Date: 2004-09-10T04:00Z

Halohydantoins
Office
of
Pesticide
Programs
Antimicrobials
Division
U.
S.
Environmental
Protection
Agency
1801
South
Bell
Street
Arlington,
VA
22202
September
8,
2004
TABLE
OF
CONTENTS
1.0
EXECUTIVE
SUMMARY
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3
2.0.
PHYSICAL
AND
CHEMICAL
PROPERTIES
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8
2.1
Chemical
Identification
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9
2.2
Physical/
Chemical
Properties
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12
3.0
HAZARD
CHARACTERIZATION
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12
3.1
Hazard
Profile
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3.2
FQPA
Considerations
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21
3.3
Dose­
Response
Assessment
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21
3.4
Endocrine
Disruption
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24
4.0
EXPOSURE
ASSESSMENT
AND
CHARACTERIZATION
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24
4.1
Summary
of
Registered
Uses
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24
4.2
Dietary
Exposure/
Risk
Pathway
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25
4.3
Water
Exposure/
Risk
Pathway
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27
4.4
Residential
Exposure/
Risk
Pathway
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28
4.4.1
Handler
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28
4.4.2.
Postapplication
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31
4.4.2.1
Carpet
Shampoo
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32
4.4.2.2
Clothing
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32
4.4.2.3
Swimming
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33
5.0
AGGREGATE
RISK
ASSESSMENTS
AND
RISK
CHARACTERIZATION
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34
5.1
Acute
Aggregate
Assessment
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34
5.2
Short­,
Intermediate­
and
Long­
term
Aggregate
Risk
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36
6.0
OCCUPATIONAL
EXPOSURE
AND
RISK
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39
6.1
Industrial
Processes
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6.2
Material
Preservatives
&
Commercial/
Institutional/
Industrial
Premises
and
Equipment
&
Swimming
Pools
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40
6.3
Agricultural
Premises
and
Aquatic
Area
Uses
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43
6.4
Postapplication
Exposure
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44
7.0
ENVIRONMENTAL
FATE
ASSESSMENT
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44
7.1
Environmental
Fate
Assessment
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44
7.2
Environmental
Fate
and
Transport
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44
8.0
ECOTOXICITY
AND
ENVIRONMENTAL
RISK
ASSESSMENT.
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8.1
Ecotoxicity
Data
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44
8.2
Environmental
Exposure
Modeling
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46
8.3
Environmental
Risk
Assessment
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46
8.4
Endangered
Species
Considerations
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47
9.0
INCIDENTS
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48
9.1
Incident
Report
Data
Associated
with
Health
Effects
of
Dihalodialkylhydantoin
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9.2
Epidemiological
Data
Associated
with
Chronic
Health
Effects
of
Halohydantoin
Exposure
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51
10.0
DATA
GAPS.
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11.0
REFERENCES
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52
Page
3
of
57
EXECUTIVE
SUMMARY
The
halohydantoins
are
a
group
of
chemicals
comprised
of
several
halogenated
compounds.
This
group
of
chemicals
includes
the
following:
1­
Bromo­
3­
chloro­
5,5­
dimethylhydantoin,
1.3­
Dibromo­
5,5­
dimethylhydantoin,
1,3­
Dichloro­
5,5­
dimethylhydantoin,
1,3­
Dichloro­
5­
ethyl­
5­
methylhydantoin,
and
non­
halogenated
hydantoins
1,3­
bis(
hydroxymethyl)­
5,5­
dimethylhydantoin,
and
1­
hydroxymethyl­
5,5­
dimethylhydantoin.
In
addition
to
these
six
hydantoins,
the
Agency
determined
that
the
5,5­
Dimethylhydantoin
and
5­
Ethyl­
5­
methylhydantoin
metabolites
of
the
halogenated
hydantoins
are
appropriate
test
substances
for
assessing
the
toxicity
of
this
group.
However,
since
the
hydroxymethylhydantoins
as
listed
above
have
the
potential
for
release
of
formaldehyde,
the
risks
associated
with
this
release
need
to
be
assessed.
The
Agency
has
determined
that
the
risks
from
exposure
to
formaldehyde
via
the
hydroxymethylhydantoins
will
be
addressed
when
the
active
ingredient
formaldehyde
is
assessed
for
reregistration
eligibility.
Therefore,
this
reregistration
eligibility
decision
(
RED)
document
assesses
the
eligibility
of
the
Halohydantoins
and
their
metabolites
for
reregistration.

These
antimicrobial
chemicals
are
registered
for
use
in
indoor
food,
indoor
non­
food,
indoor
residential,
aquatic
non­
food
residential,
aquatic
food,
aquatic
non­
food,
and
aquatic
nonfood
industrial
sites
for
control
of
bacteria,
fungi,
and
algal
slimes.

Hazard:
The
acute
toxicity
of
Halohydantoin
is
low
by
the
oral
and
dermal
routes
of
exposure
(
Toxicity
categories
III
and
IV,
respectively).
Acute
lethality
by
the
inhalation
route
is
more
significant
(
Toxicity
category
II).
The
Halohydantoins
are
significant
eye
and
skin
irritants
(
Toxicity
category
I
and
II,
respectively).
Positive
dermal
sensitization
has
also
been
observed
for
some
of
the
Halohydantions.

Non­
acute
toxicity
testing
of
hydantoins
(
DMH/
EMH)
(
including
subchronic,
developmental,
reproductive,
and
chronic
toxicity
testing)
all
show
the
presence
of
non­
specific
toxicity
only
at
relatively
high
doses
of
the
test
chemical.
Developmental
and
reproductive
toxicity
data
demonstrate
no
increase
in
susceptibility
to
the
toxic
effects
of
5,5­
dimethylhydantoin
with
the
exception
of
one
study,
where
fetal
and
litter
effects
(
increased
incidence
of
27th
presacral
vertebrae)
in
rabbits
were
observed
at
a
lower
dose
level
than
that
which
resulted
in
maternal
toxicity
(
decreased
body
weight
and
food
consumption
during
the
dosing
period)
following
treatment.
In
a
prenatal
developmental
toxicity
study
conducted
in
rabbits
with
5­
ethyl­
5­
methylhydantoin,
there
was
no
increased
susceptibility
of
the
fetuses
observed.

Chronic
toxicity
testing
of
dimethylhydantoins
in
rats
showed
a
decrement
in
body
weight
and
body
weight
gain
in
females
and
increased
mortality,
particularly
in
females.
Males
showed
increased
incidences
of
hyperplasia
of
submandibular
lymph
nodes
and
testicular
fibrinoid
vascular
degeneration
in
early
decedents.
Both
sexes
showed
increased
mammary
galactoceles
in
early
decedents
and
enlarged
pituitary
glands.
In
chronic
toxicity
studies
conducted
in
dogs,
5,5­
dimethylhydantoin
produced
slight
(
hypertrophy
in
the
adrenal
cortex
of
male
dogs
upon
microscopic
examination)
to
no
toxicity
at
or
above
the
limit
dose
of
1000
mg/
kg/
day.

Cancer
studies
in
rats
and
mice
indicated
no
systemic
effects
other
than
decreased
body
Page
4
of
57
weight
and
body
weight
gains
in
females
(
rats)
and
males
(
mice)
and
increased
hyperplasia
of
submandibular
lymph
nodes
in
males
(
rats).
No
evidence
of
carcinogenicity
of
the
test
material
was
reported.
5,5­
dimethylhydantoin
is
classified
as
`
not
likely'
to
be
a
carcinogen
based
upon
the
negative
evidence
for
carcinogenicity
in
both
the
rat
and
mouse
studies
as
well
as
the
negative
evidence
of
mutagenicity.

The
data
on
mutagenicity
of
dimethylhydantoins
shows,
in
large
part,
negative
responses
in
the
studies
conducted.
Literature
reports
indicate
a
positive
effect
for
2
in
vitro
mammalian
cytogenetic
assays
in
Chinese
Hamster
Ovary
cells.

Available
metabolism
data
indicate
that
the
dimethylhydantoins
are
excreted
unchanged
in
the
rat.
However,
it
is
known
that
hydroxymethylhydantoins
are
formaldehyde
releasers.
Therefore,
any
risk
assessment
involving
dietary
or
non­
dietary
exposure
to
the
hydroxymethylhydantoins
will
also
involve
calculating
risk
from
formaldehyde
exposure.
This
assessment
will
be
addressed
in
the
reregistration
eligibility
decision
document
for
formaldehyde.

Toxicity
Endpoints:
On
July
25,
2000
,
the
Health
Effects
Division
(
HED)
Hazard
Identification
Assessment
Review
Committee
(
HIARC)
reviewed
the
recommendations
of
the
toxicology
reviewer
for
5,5­
dimethylhydantoin
(
a
chemical
representative
of
hydantoin
toxicity)
with
regard
to
the
acute
and
chronic
Reference
Doses
(
RfDs)
and
the
toxicological
endpoint
selection
for
use
as
appropriate
in
occupational/
residential
exposure
risk
assessments.
The
potential
for
increased
susceptibility
of
infants
and
children
from
exposure
to
this
hydantoin
was
also
evaluated
as
required
by
the
Food
Quality
Protection
Act
(
FQPA)
of
1996.
Endpoints
were
established
for
the
hydantoins
and
a
report
issued.
A
summary
of
the
endpoints
selected
is
provided
at
the
end
of
this
chapter.

Dietary
Endpoints:
Acute
and
chronic
dietary
endpoints
were
selected
to
be
100
mg/
kg/
day
for
females
13­
50
based
on
a
developmental
toxicity
study
on
rabbits,
in
which
skeletal
variations
were
seen
at
500
mg/
kg/
day.
The
Acute
and
Chronic
RfD
for
this
population
is
1
mg/
kg.
A
chronic
dietary
endpoint
of
300
mg/
kg/
day
was
selected
for
the
general
population
based
on
a
chronic
toxicity
study
on
rats,
in
which
decreased
body
weight,
weight
gain,
and
lymph
node
hyperplasia
were
observed.
The
Chronic
RfD
for
the
general
population
is
3
mg/
kg/
day.

Oral
Endpoints:
The
incidental
short­
term
oral
endpoint
was
selected
to
be
500
mg/
kg/
day,
based
a
developmental
toxicity
study
on
rabbits,
in
which
decreased
body
weight
gain
in
maternal
rabbits
at
1000
mg/
kg/
day.
The
intermediate
term
oral
endpoint
was
selected
to
be
300
mg/
kg/
day,
based
on
a
subchronic
oral
toxicity
study
in
which
decreased
body
weight
and
liver
weight
were
observed
at
1000
mg/
kg/
day.

Dermal
Endpoints:
The
short­,
intermediate­,
and
long­
term
dermal
endpoints
were
selected
to
be
390
mg/
kg/
day.
No
systemic
toxicity
was
found
at
the
highest
dose
tested
in
a
subchronic
toxicity
study
on
rats.
Page
5
of
57
Inhalation
Endpoints:
The
short­
term
inhalation
endpoint
was
selected
to
be
the
same
as
the
oral
endpoint
of
100,
due
to
skeletal
effects
in
offspring
at
500
mg/
kg/
day
in
a
developmental
toxicity
study
in
rabbits.

FQPA
Safety
Factor:
Although
there
is
quantitative
evidence
of
increased
sensitivity
of
neonatal
rabbits,
the
HIARC
considered
this
effect
not
indicative
of
susceptibility,
based
upon
the
very
high
dose
level
at
which
the
effect
occurred,
the
minimal
nature
of
the
effect,
and
the
likelihood
that
the
effect
was
due
to
a
greater
dose
received
by
pups
from
ingestion
of
both
milk
and
feed
during
the
lactational
period.
Therefore,
the
HIARC
recommended
that
the
special
hazard­
based
FQPA
safety
factor
could
be
removed
for
the
hydantoins
and
that
the
use
of
a
standard
uncertainty
factor
of
100
would
be
sufficient.

Dietary
Exposure:
The
Agency
has
carried
out
the
dietary
exposure
and
risk
assessment
for
use
of
Halohydantoins
as
a
slimicide
in
food
contact
paper
and
paperboard,
and
for
use
as
a
preservative
in
inorganic
slurries
which
are
used
as
fillers
for
food
contact
paper
and
paperboard.
The
acute
dietary
exposure
for
an
adult
female
is
0.046%
of
the
acute
Population
Adjusted
Dose
(
PAD).
The
highest
chronic
exposure
occurred
in
adult
females
(
0.0153%
of
the
chronic
PAD).
All
dietary
exposures
calculated
were
well
below
the
Agency's
level
of
concern
(
100%
of
aPAD
or
cPAD).

Water
Exposure
and
Risk:
AD
has
considered
the
registered
uses
of
Halohydantoins
and
the
available
data
on
persistence
and
mobility.
The
Agency
is
presently
relying
on
predicted
environmental
concentrations
(
PECs)
of
pesticides
in
surface
water
to
estimate
drinking
water
exposures
to
Halohydantoins.
Out
of
all
the
uses
of
the
pesticide,
the
once­
through
cooling
water
system
can
be
expected
to
have
the
greatest
impact
on
the
water,
since
the
scenario
has
the
greatest
quantity
of
effluent
being
produced
and
has
the
greatest
chance
of
bacterial
fouling
and
need
for
pesticide.
Using
the
PDM4
model,
the
short­
term
EEC
in
surface
water
uses
estimated
to
be
36
ug/
L.
The
chronic
maximum
EEC
using
this
model
was
determined
to
be
313
ug/
L.
Based
on
current
Agency
policy,
drinking
water
level
of
comparison
(
DWLOCs)
are
compared
to
the
EEC.
When
the
EEC
is
greater
than
the
DWLOC,
AD
considers
the
estimate
of
aggregate
risk
to
exceed
the
Agency's
level
of
concern.

Residential
Exposure
and
Risk:
Halohydantoins
may
be
added
to
residential­
use
products
used
to
control
bacteria
and
fungicide.
A
number
of
such
products
have
been
identified,
including
household
cleaning
products,
paint,
adhesives,
and
deodorizers.
For
the
purposes
of
this
screening
level
assessment,
handler
scenarios
have
been
developed
that
encompass
multiple
products
but
still
represent
a
worst­
case
scenario
for
all
products
represented.
Table
12
shows
the
handler
scenarios
considered
in
this
assessment.
Detergents,
soaps,
household
cleaning
products,
and
carpet
shampoo
have
been
grouped
together.
Of
these
products,
household
cleaning
products,
which
should
yield
the
greatest
amount
of
handler
exposure
to
the
chemical,
was
selected
for
analysis.
In­
tank
toilet
tablets,
which
are
placed
into
toilet
tanks,
differ
from
the
other
household
cleaning
products
in
that
they
are
not
liquid.
These
tablets
were
evaluated
in
a
separate
scenario.
Adhesives,
caulks,
and
paints
have
been
grouped
together
for
evaluation.
There
are
no
risks
of
concern
of
any
of
the
handler
or
post
application
residential
exposure
scenarios
assessed.
Page
6
of
57
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".
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
Halohydantoins,
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
as
needed.

Dermal
Aggregate
Exposure:
Short­,
intermediate­,
and
long­
term
aggregate
dermal
risks
are
considered
together
since
the
exposure
and
toxicity
endpoints
are
identical
for
dermal
exposures
for
all
three
durations.
It
was
assumed
that
a
resident
would
apply
paint
using
either
a
paintbrush
or
an
aerosol
can.
The
total
dermal
MOE
for
an
adult
resident
that
could
simultaneously
contact
clothing,
cleaning
products,
toilet
cleaners,
swimming
pools,
and
paint
treated
with
the
pesticide
is
132
and
132
for
competitive
and
non­
competitive
swimmers,
which
is
greater
than
the
target
MOE
of
100,
and
thus
does
not
exceed
the
Agency's
level
of
concern.

For
children,
the
aggregate
dermal
MOE
of
107
was
greater
than
the
target
of
100,
indicating
no
aggregate
risk
of
concern
for
dermal
exposure.

In
addition
to
dermal
exposure
of
children
on
carpet,
infants
crawling
on
treated
carpets
will
also
pose
a
risk
of
exposure
to
Halohydantoins
via
incidental
oral
exposure.
The
calculated
Margin
of
Exposure
(
4200)
is
above
the
Agency's
level
of
concern.
This
is
not
aggregated
with
other
scenarios
as
there
is
only
one
scenario,
and
the
endpoint
defining
effects
by
this
route
is
not
similar
to
the
dermal
or
inhalation
routes.

Inhalation
Aggregate
Exposure:
As
only
a
short­
term
inhalation
endpoint
was
selected,
only
short­
term
aggregate
exposures
were
considered.
It
was
assumed
that
a
resident
would
apply
paint
using
either
a
paintbrush
or
an
aerosol.
The
total
inhalation
MOE
for
an
adult
resident
that
could
simultaneously
contact
toilet
cleaners,
paint
treated
with
the
pesticide,
and
swimming
pools
is
9940
for
competitive
swimmers
and
11976
for
non­
competitive
swimmers,
which
is
greater
than
the
target
MOE
of
100,
and
thus
does
not
exceed
the
Agency's
level
of
concern.

Occupational
Exposure
and
Risk:
Several
different
sources
of
handler
exposure
data
were
used
to
assess
occupational
and
residential
Halohydantoins
risks.
Data
from
the
both
proprietary
Chemical
Manufacturers
Association
(
CMA)
antimicrobial
exposure
study
and
the
Pesticide
Handlers
Exposure
Database
(
PHED)
were
used.
Page
7
of
57
Out
of
all
occupational
scenarios
considered,
an
MOE
lower
than
the
target
MOE
was
found
for
only
two
scenarios
 
placing
tablets
into
public
swimming
pools
wearing
baseline
protection
(
Dermal
MOE=
46
but
mitigated
with
the
use
of
gloves
MOE=
7500),
that
have
not
been
mitigated
at
this
time,
and
greenhouse
and
nursery
irrigation
systems
(
MOE
=
14
for
use
of
tablets
with
gloves,
MOE
=
2
for
use
of
granules
without
gloves).
However,
the
greenhouse
use
may
be
overestimates
of
the
true
risk
associated
with
use
of
these
products.
The
product
labels
state
that
gloves
should
be
worn
when
placing
tablets
into
swimming
pools,
and
the
PPE
calculations
should
be
more
applicable
to
public
swimming
pool
scenarios.
And
the
calculations
to
determine
exposure
for
irrigation
systems
were
based
on
very
conservative
estimates,
for
lack
of
better
data.
There
are
a
number
of
uncertainties
associated
with
this
assessment.
In
general,
conservative
values
were
used
in
cases
where
data
were
lacking.
Assessments
for
these
scenarios
should
be
considered
as
screening
assessments,
and
additional
use
information
for
greenhouse
irrigations
should
be
submitted.

Environmental
Fate:
The
Agency
does
not
have
a
complete
database
for
environmental
fate
studies
on
Halohydantoins.
However,
hydrolysis
appears
to
be
the
major
route
for
dissipation.
The
rapid
hydrolysis,
under
abiotic
conditions,
show
half­
lives
of
less
than
30
days
in
pH
5,
pH
7,
and
pH
9
(
in
buffered
solutions),
which
indicated
that
hydrolysis
is
an
early
step
in
the
degradation
process.
However,
the
major
degradate,
dimethylhydantoin
(
DMH),
was
hydrolytically
stable
at
pH
5,
pH
7,
and
pH
9
and
may
possibly
leach
in
the
soil
profile
or
move
with
surface
water
runoff
and
may
pose
environmental
concerns.
The
Agency
lacks
any
data
on
Halohydantoins
as
far
as
mobility
(
soil
column
leaching)
is
concerned,
as
well
as
binding
constants
to
soils
to
indicate
if
Halohydantoinss
will
be
persistent
in
soils.
Because
of
lack
of
data,
the
Agency
cannot
assess
if
Halohydantoinss
are
bioaccumulative
and
if
these
can
be
a
source
of
concern
for
the
aquatic
organisms.
There
is
environmental
concern
for
soil
or
surface
water
contamination
from
the
major
degradate
DMH,
as
DMH
is
hydrolytically
and
photolytically
stable.
No
additional
fate
data
on
dimethylhydantoins
are
available
to
further
assess
fate
of
this
chemical.

Ecological
Hazard:
DMH
was
considered
to
be
the
moiety
of
concern
for
environmental
and
ecotoxicology.
DMH
shows
low
toxicity
to
birds,
mammals,
and
freshwater
and
marine/
estaurine
fish
and
invertebrates.
No
toxicity
data
were
available
to
assess
the
phytotoxicity
of
DMH
or
other
hydantoin
compounds;
these
data
are
required
to
support
the
once­
through
cooling
uses
of
hydantoin
products
(
see
Data
Gaps
section
of
this
document).

Environmental
Exposure
and
Modeling:
The
PDM4
Model
was
used
to
estimate
exposure
from
once­
through
cooling
tower
uses.
The
details
of
this
model
are
found
in
the
Environmental
Modeling
Chapter
of
this
document.
A
low­
flow
power
plant
(
100
+
10
million
gallons
per
day)
was
used
as
the
scenario
providing
the
maximum
concentrations
of
DMH
in
the
receiving
water,
e.
g.,
the
"
worst
case"
scenario.
Peak
EECs
ranged
from
36.0
ppb
over
4
days
to
313
ppb
over
60
days.
Actual
concentrations
in
receiving
waters
are
likely
lower,
and
will
likely
not
show
the
increasing
trend
indicated
by
these
results,
due
to
higher
flow
rates
and
possible
degradation/
dissipation
of
DMH
by
mechanisms
other
than
hydrolysis.

Environmental
Risk
Assessment:
Terrestrial
exposure
modeling
was
not
conducted,
but
Page
8
of
57
exposure
from
the
registered
uses
of
hydantoin
products
is
expected
to
be
low,
and
risk
to
birds
and
mammals
is
not
anticipated.
Risk
to
terrestrial/
semi­
aquatic
plants
could
not
be
assessed
due
to
a
lack
of
phytotoxicity
data.

Using
the
very
conservative
EECs
provide
by
modeling
the
low­
flow
power
plant,
no
LOCs
are
exceeded.
Other
uses
of
hydantoin
products
are
indoor
or
contained
(
e.
g.,
swimming
pool)
uses,
and
should
not
result
in
appreciable
environmental
exposure
when
products
are
used
as
labeled.
Risk
to
freshwater
fish
and
aquatic
invertebrates
is
not
anticipated
from
the
use
of
hydantoins
in
once­
through
cooking
systems.
Marine/
estuarine
fish
are
generally
less
sensitive
that
freshwater
fish
to
hydantoins,
and
marine/
estuarine
invertebrates
are
comparably
as
sensitive
to
DMH
as
freshwater
invertebrates,
so
the
freshwater
RQ
are
presumed
to
be
protective
of
marine/
estuarine
species.
Risk
to
aquatic
plants
cannot
be
assessed
due
to
the
lack
of
phytotoxicity
data.

Endangered
Species:
Risk
to
endangered
birds
and
mammals
is
not
anticipated
from
the
use
of
hydantoin
products
due
to
low
exposure
and
low
toxicity.
Calculated
RQs
for
fish
and
aquatic
invertebrates
from
the
once­
through
cooling
use
are
well
below
LOCs
for
endangered
species;
other
use
of
hydantoin
products
are
indoor
or
contained
(
e.
g.,
swimming
pool)
uses,
and
should
not
result
in
appreciable
environmental
exposure
when
products
are
used
as
labeled.
Therefore,
risk
to
endangered
fish
and
aquatic
invertebrate
species
is
not
anticipated
from
the
use
of
hydantoin
products.
Risk
to
endangered
plants
cannot
be
addressed
due
to
the
lack
of
phytotoxicity
data.

Incident
Reports:
There
are
many
incidences
that
have
been
reported
associated
with
exposure
to
end­
use
products
containing
Halohydantoins.
Dermal,
ocular
and
inhalation
are
the
primary
routes
of
exposure.
Most
of
the
incidences
are
related
to
irritation
and/
or
allergic
type
reaction.
The
most
common
symptoms
reported
for
cases
of
dermal
exposure
were
skin
irritation/
burning,
rash,
itching,
skin
discoloration/
redness,
blistering,
allergic
type
reactions
including
hives,
welts,
allergic
contact
dermatitis,
and
bleeding
also
have
been
reported.
The
most
common
symptoms
reported
for
cases
of
ocular
exposure
were
eye
irritation/
burning.
Eye
pain
and
swelling
of
eyes
also
has
been
reported
in
some
incidences.
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,
headache.
Seizure
and
heart
palpitation
also
have
been
reported.
Although
oral
exposure
is
considered
a
minor
route
of
exposure
for
Halohydantoins
use,
irritation
to
mouth/
throat/
nose,
vomiting/
nausea/
abdominal
pain
have
been
reported
in
cases
of
ingestion.

Data
Gaps:
The
following
ecological
effects
data
are
required
to
support
the
oncethrough
cooling
system
uses
of
hydantoin
products:

72­
4b/
850.1400
Invertebrate
life­
cycle
testing­
freshwater
TGAI1
123­
1/
850.4225
Seedling
emergence
dose
 
response
in
rice
TEP2
Page
9
of
57
123­
1/
850.4250
Vegetative
vigor
dose­
response
in
rice
TEP
123­
2/
850.4400
Aquatic
vascular
plant
dose­
response
toxicity­
Lemna
sp.
TGAI
or
TEP
123­
2/
850.5400
Acute
algal
dose­
response
toxicity
­
4
species
TGAI
or
TEP
1TGAI=
technical
grade
active
ingredient
2TEP=
typical
end­
use
product
Toxicology
data
gap:
82­
4/
870.3465
90­
Day
Inhalation
2.0
PHYSICAL/
CHEMICAL
PROPERTIES
CHARACTERIZATION
The
halohydantoins
are
a
group
of
chemicals
composed
of
several
halogenated
compounds
(
i.
e.
a
central
organic
hydantoin
ring
moiety
(
either
dimethylhydantoin
or
ethylmethylhydantoin)
to
which
halogen
atoms
(
bromine
and/
or
chlorine)
can
be
attached
at
both
the
1
and
3
positions
on
the
hydantoin
ring),
as
well
as
hydroxymethylhydantoin
compounds
(
1,3­
bis(
hydroxymethyl)­
5,5­
dimethylhydantoin
and
1­
hydroxymethyl)­
5,5­
dimethylhydantoin).

2.1
Chemical
Identification
The
common
names,
chemical
names,
empirical
formulas,
and
CAS
numbers
of
the
halohydantoins
are
presented
in
Table
1.

Table
1.
Common
Names,
Chemical
Names,
Empirical
Formulas,
and
CAS
Numbers
Common
Name
Chemical
Name
Empirical
Formula
CAS
No.

Dichlorodimethylhydantoin
1,3­
dichloro­
5,5­
dimethylhydantoin
C5H6Cl2N2O
2
118­
52­
5
Bromochlorodimethylhydantoin
1­
Bromo­
3­
chloro­
5,5­
dimethylhydantoin
C5H6BrClN2
O2
16079­
88­
2
Dichloroethylmethylhydantoin
1,3­
dichloro­
5­
ethyl­
5­
methylhydantoin
C6H8Cl2N2O
2
89415­
87­
2
In
addition
to
the
products
listed
in
Table
1,
two
additional
formulations
are
also
registered:
Dantogard
(
EPA
Reg#
6836­
119)
and
Glycoserve
(
EPA
Reg#:
6836­
112).
Their
chemical
names,
PC
Codes
are
listed
as
follows:

1.
Ingredients
of
Dantogard
are:
1,3­
bis(
hydroxymethyl)­
5,5­
dimethylhydantoin
(
PC
Code:
115501)
And
Hydroxy­
5,5­
dimethylhydantoin
(
PC
Code:
115502)
September
1988
label
of
this
product
states:
"
The
product
contains
1.5%
formaldehyde"

2.
Ingredients
of
Glycoserve
are
the
same
as
the
Dantogard.
The
two
ingredients
vary
in
percentages
in
the
two
formulations.

The
label
of
this
product
states:
"
The
product
contains
at
a
maximum
concentration
of
2%
formaldehyde".
Page
10
of
57
NH
HN
O
O
Hydantoin
NH
HN
O
O
CH3
CH3
5,5­
Dimethylhydantoin
N
N
Cl
Cl
O
O
CH3
CH3
1,3­
Dichloro­
5,5­
Dimethylhydantoin
N
N
Cl
Br
O
O
CH3
CH3
1­
Chloro,
3­
Bromo­
5,5­
Dimethylhydantoin
N
N
Cl
Cl
O
O
CH3
C2H5
1,3­
Dichloro­
5­
Methyl,
5­
Ethylhydantoin
The
information
about
these
chemicals
are
included
here
as
not
only
the
formulations
contain
formaldehyde
as
impurity
as
stated
on
the
labels
but
these
are
also
formaldehyde
releasers.
However,
these
two
chemicals
are
not
assessed
here
along
with
other
dimethylhydantoins
derivatives
but
will
be
assessed
in
the
upcoming
RED
on
formaldehyde.

Structures
of
hydantoin
and
its
derivatives
considered
in
this
document
are
below:
Page
11
of
57
N
N
CH2OH
CH2OH
O
O
H3C
CH3
1,3­
bis(
hydroxymethyl)­
5,5Dimethylhydantoin
NH
N
CH2OH
O
O
H3C
H3C
Hydroxymethyl­
5,5­
Dimethylhydantoin
Page
12
of
57
2.2
Physical
and
Chemical
Properties
Physical
and
chemical
properties
of
DantobromTM
S
are
shown
in
Table
2.
Dantobrom
 
S
is
one
of
a
number
of
pesticides
containing
halohydantoins.

Table
2.
Physical
and
Chemical
properties
of
DantobromTM
S
Parameter
Value
Color
Off­
white
Physical
State
Powder
Odor
Slight
chlorine
odor
Stability
Dantobrom
 
S
is
stable
in
the
dry
state.
It
decomposes
exothermally
at
180

C.
It
is
attacked
by
strong
alkalies,
acids,
and
moisture.

Oxidation/
Reduction
Oxidizer
pH
of
water
solution,
1%
slurry
at
25oC
3.6
Melting
point
between
120
and
148oC
Kow
unknown
Water
solubility
at
25oC
0.54
g
/
100
g
Vapor
Pressure
NA
The
impurities
formed
during
the
production
of
DantobromTM
S
include
sodium
chloride
and
water
(
gaseous
form).
Preliminary
analysis
of
Glychlor
and
Dantochlor
revealed
quantities
of
DMH
radical,
MEH
radical,
active
chlorine,
chloroform
insolubles,
and
volatiles.

3.0
HAZARD
CHARACTERIZATION
3.1
Hazard
Profile
A
detailed
hazard
assessment
for
Halohydantoins
is
presented
in
the
attached
appendix.
The
acute
toxicity
of
the
hydantoins
shown
in
Table
3a
is
low
by
the
oral
and
dermal
routes
of
exposure
(
Toxicity
categories
III
and
IV,
respectively).
Acute
lethality
by
the
inhalation
route
is
more
significant
(
Toxicity
category
II).
The
dimethylhydantoins
are
significant
eye
and
skin
irritants
(
Toxicity
category
I
and
II,
respectively).
Positive
dermal
sensitization
has
also
been
observed.
Page
13
of
57
Table
3a.
Acute
Toxicity
of
Halohydantoins
Guideline
No./
Study
Type
MRID
No.
(
TRID
No.)
Results
Toxicity
Categor
y
5,5­
Dimethylhydantoin
870.1100
Acute
oral
(
gastric
intubation)
toxicity
(
limit
test)­
Mouse
45738401
LD50
(
combined)
>
5,000
mg/
kg
IV
1­
Bromo­
3­
chloro­
5,5­
dimethylhydantoin
870.1100
Acute
oral
toxicity­
Rat
93074006,
00128244
(
4226­
010­
01)
LD50(
males)
=
1,350
mg/
kg
LD50(
females)
=
1,520
mg/
kg
LD50(
combined)
=
1,390
mg/
kg
III
870.1100
Acute
oral
toxicity­
Rat
93077008,
00147325
(
4600­
950­
21)
LD50(
males)
=
1,037
mg/
kg
LD50(
females)
=
860
mg/
kg
LD50(
combined)
=
929
mg/
kg
III
870.1300
Acute
inhalation
toxicity­
Rat
43654101
LC50(
males)
=
0.157
mg/
L
LC50(
females)
=
0.213
mg/
L
LC50(
combined)
=
0.168
mg/
L
II
870.2500
Acute
dermal
irritation­
Rabbit
93074011,
93075014,
00128242
(
4225­
014­
10)
severe
skin
irritant
I
870.2500
Acute
dermal
irritation­
Rabbit
93077009,
00147326
(
4600­
950­
22)
severe
skin
irritant
I
870.2600
Skin
sensitization­
Guinea
pig
41670001
positive
sensitizer
N/
A
1,3­
Dibromo­
5,5­
dimethylhydantoin
870.1100
Acute
oral
toxicity­
Rat
93076011,
00137105
(
4334­
012­
01)
LD50
=
760
mg/
kg
III
870.1200
Acute
dermal
toxicity­
Rabbit
93076025,
00137110
(
4334­
012­
07)
LD50
cannot
be
ascertained
(
study
is
classified
as
Unacceptable/
non­
guideline
­­

870.2500
Acute
dermal
irritation­
Rabbit
93076017,
00137109
(
4334­
012­
05)
severe
skin
irritant
I
1,3­
Dichloro­
5,5­
dimethylhydantoin
870.1200
Acute
dermal
toxicity­
Rabbit
93076013,
00084176
(
2402­
448­
05)
LD50
>
20,000
mg/
kg
IV
Page
14
of
57
870.2500
Acute
dermal
irritation­
Rabbit
93076017,
00137109
(
2402­
448­
01)
severe
skin
irritant
I
Non­
acute
toxicity
testing
of
hydantoins
(
including
subchronic,
developmental,
reproductive,
and
chronic
toxicity
testing)
all
show
the
presence
of
non­
specific
toxicity
only
at
relatively
high
doses
of
the
test
chemical
(
Table
3b).
Developmental
and
reproductive
toxicity
data
demonstrate
no
increase
in
susceptibility
to
the
toxic
effects
of
dimethylhydantoin
with
the
exception
of
one
study,
where
fetal
and
litter
effects
(
increased
incidence
of
27th
presacral
vertebrae)
in
rabbits
were
observed
at
a
lower
dose
level
than
that
which
resulted
in
maternal
toxicity
(
decreased
body
weight
and
food
consumption
during
the
dosing
period)
following
treatment.
In
a
prenatal
developmental
toxicity
study
conducted
in
rabbits
with
ethylmethylhydantoin,
there
was
no
increased
susceptibility
of
the
fetuses
observed.

Chronic
toxicity
testing
of
dimethylhydantoins
in
rats
showed
a
decrement
in
body
weight
and
body
weight
gain
in
females
and
increased
mortality,
particularly
in
females.
Males
showed
increased
incidences
of
hyperplasia
of
submandibular
lymph
nodes
and
testicular
fibrinoid
vascular
degeneration
in
early
decedents.
Both
sexes
showed
increased
mammary
galactoceles
in
early
decedents
and
enlarged
pituitary
glands.
In
two
chronic
toxicity
studies
conducted
in
dogs,
dimethylhydantoin
produced
slight
(
enlarged
pituitary
glands)
to
no
toxicity
at
or
above
the
limit
dose
of
1000
mg/
kg/
day.

Cancer
studies
in
rats
and
mice
indicated
no
systemic
effects
other
than
decreased
body
weight
and
body
weight
gains
in
females
(
rats)
and
males
(
mice)
and
increased
hyperplasia
of
submandibular
lymph
nodes
in
males
(
rats).
No
evidence
of
tumorigenicity
of
the
test
material
was
reported.
5,5­
dimethylhydantoin
is
classified
as
`
not
likely'
to
be
a
carcinogen
based
upon
the
negative
evidence
for
carcinogenicity
in
both
the
rat
and
mouse
studies
as
well
as
the
negative
evidence
of
mutagenicity.

The
data
on
mutagenicity
of
dimethylhydantoins
shows,
in
large
part,
negative
responses
in
the
studies
conducted.
A
literature
report
indicates
a
positive
effect
for
induction
of
lethal
mutations
in
Drosophila
melanogaster.

Available
metabolism
data
indicate
that
the
dimethylhydantoins
are
excreted
unchanged
in
the
rat.
However,
it
is
known
that
methylhydantoins
are
formaldehyde
releasers.
Therefore,
any
risk
assessment
involving
dietary
or
non­
dietary
exposure
to
the
methylhydantoins
will
also
involve
calculating
risk
from
formaldehyde
exposure
(
This
risk
assessment
will
be
addressed
in
the
reregistration
eligibility
decision
document
for
formaldehyde).
Page
15
of
57
Table
3b.
Subchronic,
Chronic
and
Other
Toxicity
Tables
Guideline
No./
Study
Type/
Substance
Purity
MRID
No.
(
year)/
Classification/
Doses
Results
Subchronic
Toxicity
870.3100
90­
Day
oral
toxicity
rodents
­
Rat
1DMH
purity
>
99.5%
42009201
(
1991)
Acceptable/
guideline0,
100,
300,
1000
mg/
kg/
day
NOAEL
=
greater
than
or
equal
to
1000
mg/
kg/
day
(
highest
dose
tested)
LOAEL
=
greater
than
1000
mg/
kg/
day
(
not
established).

28­
Day
oral
toxicity
­
Mouse
DMH
purity
100%
45738402
NOAEL
=
greater
than
or
equal
to
50,000
ppm
[
males:
10,057,
females:
14,972
mg/
kg/
day]
(
highest
dose
tested)
LOAEL
=
greater
than
50,000
ppm
[
males:
10,057,
females:
14,972
mg/
kg/
day]
(
not
established).

870.3150
90­
Day
oral
toxicity
in
nonrodents
No
study
available.

870.3200
21/
28­
Day
dermal
toxicity
No
study
available.

870.3250
90­
Day
dermal
toxicity
DMH
purity
99.8%
43173901
(
1994)
core/
guideline
0,
39,
130,
390
mg/
kg/
day
This
study
is
classified
as
Acceptable­
Guideline
and
it
satisfies
the
guideline
requirements
for
a
subchronic
toxicity
study
[
OPPTS
870.3250
(
§
82­
1b)]
in
rats.
Higher
doses
of
DMH
were
not
possible
in
this
study;
thus,
although
a
limit
dose
was
not
tested,
the
study
is
considered
acceptable.
NOAEL
=
greater
than
or
equal
to
390
mg/
kg/
day
(
highest
dose
tested)
LOAEL
=
greater
than
390
mg/
kg/
day
(
not
established)
Page
16
of
57
Guideline
No./
Study
Type/
Substance
Purity
MRID
No.
(
year)/
Classification/
Doses
Results
870.3465
90­
Day
inhalation
toxicity
No
study
available.
Page
17
of
57
Guideline
No./
Study
Type/
Substance
Purity
MRID
No.
(
year)/
Classification/
Doses
Results
Developmental/
Reproductive
Toxicity
870.3700
Prenatal
developmental
in
rats
DMH
purity
99.8%
42432701
(
1992)
Core
Minimum/
Guideline
0,
100,
300,
1000
mg/
kg/
day
Maternal
Toxicity
NOAEL
=
300
mg/
kg/
day
Maternal
Toxicity
LOAEL
=
1000
mg/
kg/
day
based
on
the
transient
decrease
in
body
weight
gain
during
gestation
days
9­
12.

Developmental
Toxicity
NOAEL
=
greater
than
or
equal
to1000
mg/
kg/
day
(
highest
dose
tested)
Developmental
Toxicity
LOAEL
=
greater
than
1000
mg/
kg/
day
(
not
established)

870.3700
Prenatal
developmental
in
nonrodents
­
Rabbits
DMH
purity
96­
98.7%
42413101
(
1992)
core/
guideline
0,
100,
500,
1000
mg/
kg/
day
Maternal
Toxicity
NOAEL
=
500
mg/
kg/
day
Maternal
Toxicity
LOAEL
=
1000
mg/
kg/
day
based
on
decreased
body
weight
gain
and
food
consumption
during
the
dosing
period.

Developmental
Toxicity
NOAEL
=
100
mg/
kg/
day
Developmental
Toxicity
LOAEL
=
500
mg/
kg/
day
based
on
the
increased
incidence
of
the
27th
presacral
vertebrae.

870.3700
Prenatal
developmental
in
nonrodents
­
Rabbits
2EMH
purity
>
99.5%
42205401
(
1992)
acceptable
Phase
I:
0,
50,
125,
or
375
mg/
kg/
day
Phase
II:
0
or
1000
mg/
kg/
day
Maternal
Toxicity
NOAEL
=
375
mg/
kg/
day
Maternal
Toxicity
LOAEL
=
1000
mg/
kg/
day,
based
on
mortality,
reduced
body
weights
gains
and
reduced
food
consumption.

Developmental
Toxicity
NOAEL
=
375
mg/
kg/
day
Developmental
Toxicity
LOAEL
=
1000
mg/
kg/
day,
based
on
decreased
fetal
body
weights.

870.3800
Reproduction
and
fertility
effects
DMH
purity
96­
98.7%
42462502
(
1992)
Core/
Guideline
0,
250,
500,
1000
mg/
kg/
day
(
20,000
ppm)

20,000
ppm
(
1322
and
1602
mg/
kg/
day,
respectively)
for
male
and
female
rats
Parental/
Systemic
NOAEL
=
greater
than
or
equal
to1000
mg/
kg/
day
(
highest
dose
tested)
Parental/
Systemic
LOAEL
=
greater
than
1000
mg/
kg/
day
(
not
established).

Offspring
Toxicity
NOAEL
=
greater
than
or
equal
to1000
mg/
kg/
day
(
highest
dose
tested)
Offspring
Toxicity
LOAEL
=
greater
than
1000
mg/
kg/
day
(
not
established).
Page
18
of
57
Guideline
No./
Study
Type/
Substance
Purity
MRID
No.
(
year)/
Classification/
Doses
Results
Chronic
Toxicity/
Carcinogenicity
870.4100
Chronic
toxicity
rodents
DMH
purity
99.8%
43397702
(
1994)
core/
guideline
[
870.4300
(
§
83­
5)]
0,
100,
300,
1000
mg/
kg/
day
Systemic
Toxicity
NOAEL
=
300
mg/
kg/
day
Systemic
Toxicity
LOAEL
=
1000
mg/
kg/
day,
based
on
decreases
in
body
weight
and
body
weight
gain
in
females
and
hyperplasia
of
submandibular
lymph
nodes
in
males.

No
evidence
of
carcinogenicity
870.4100
Chronic
toxicity
rodents
DMH
purity
97.3%,
97.1%,
and
93.5%
44095901
(
1996)
acceptable/
guideline
0,
100,
320,
1000
mg/
kg/
day
Systemic
Toxicity
NOAEL
=
320
mg/
kg/
day
Systemic
Toxicity
LOAEL
=
1000
mg/
kg/
day,
based
on
enlarged
pituitary
glands
in
decedents
of
both
sexes,
increased
mortality
occurring
early
in
(
especially)
females,
increased
mammary
galactoceles
in
early
decedents
of
both
sexes
and
testicular
fibroid
vascular
degeneration
in
early
decedent
males.

At
the
doses
tested,
there
was
not
a
treatment
related
increase
in
tumor
incidence
after
105
weeks
of
treatment
with
DMH.
No
evidence
of
carcinogenicity
870.4100
Chronic
toxicity
dogs
DMH
purity
97.4%
43813301
(
1996)
NOAEL
=
greater
than
1000
mg/
kg/
day
(
highest
dose
tested
LOAEL
=
greater
than
1000
mg/
kg/
day
(
not
established)

870.4100
Chronic
toxicity
dogs
DMH
purity
98.9%
43553101
(
1995)
acceptable
Males:
0,
120,
342,
or
1506
mg/
kg/
day
Females:
0,
121,
414,
or
1352
mg/
kg/
day
NOAEL
=
12000
ppm
(
342
mg/
kg/
day)
LOAEL
=
40000
ppm
(
1506
mg/
kg/
day),
based
on
enlarged
adrenal
glands
in
male
dogs,
shown
by
microscopic
examination
to
exhibit
hypertrophy
in
the
adrenal
cortex.

870.4200
Carcinogenicity
rats
DMH
purity
99.8%
43397702
(
1994)
core/
guideline
0,
100,
300,
1000
mg/
kg/
day
See
Chronic
Toxicity
in
Rodents
­
Rats
No
evidence
of
carcinogenicity
There
were
no
increases
in
tumor
incidences
for
the
DMH
treated
groups
when
compared
to
the
control
group.
This
study
is
classified
as
Page
19
of
57
Guideline
No./
Study
Type/
Substance
Purity
MRID
No.
(
year)/
Classification/
Doses
Results
870.4200
Carcinogenicity
rats
DMH
purity
97.3%,
97.1%,
and
93.5%
44095901
(
1996)
acceptable/
guideline
0,
100,
320,
1000
mg/
kg/
day
See
Chronic
Toxicity
in
Rodents
­
Rats
No
evidence
of
carcinogenicity
870.4300
Carcinogenicity
mice
DMH
purity
99.8%
43397701
(
1994)
Acceptable­
guideline
[
870.4200
(
§
83­
2)]
0,
400,
1850,
8500
ppm
(
0,
100,
300,
1000
mg/
kg/
day)
Systemic
Toxicity
NOAEL
=
300
mg/
kg/
day
Systemic
Toxicity
LOAEL
=
1000
mg/
kg/
day
based
on
decreases
in
body
weight
and
body
weight
gain
in
males.

No
evidence
of
carcinogenicity
870.4300
Carcinogenicity
mice
DMH
purity
94.9­
97.1%
44063901
(
1996)
Acceptable/
guideline
[
870.4200
(
§
83­
2b)]
0,
100,
320,
1000
mg/
kg/
day
Systemic
Toxicity
NOAEL
=
greater
than
or
equal
to
1000
mg/
kg/
day
(
highest
dose
tested).
Systemic
Toxicity
LOAEL
=
greater
than
1000
mg/
kg/
day
(
not
established).

Under
the
conditions
of
this
study,
there
was
no
evidence
of
carcinogenic
potential
in
mice
following
treatment
with
DMH
and
the
dosing
was
considered
adequate
because
the
highest
dose
of
1000
mg/
kg/
day
represents
a
"
limit
dose."

No
evidence
of
carcinogenicity
Mutagenicity
Gene
Mutation
870.5100
Ames
Salomella
Assay
DMH
purity
97.0%
164036
(
265457)
(
1986)
acceptable
100,
500,
2500,
5000,
10000

g/
plate
No
evidence
of
a
mutagenic
response
Gene
Mutation
870.5100
Ames
Salomella
Assay
EMH
purity
not
reported
137095
(
1982)
acceptable
67,
333,
1667,
3333
or
6666
µ
g/
plate
No
evidence
of
a
mutagenic
response
Gene
Mutation
870.5100
Ames
Salomella
Assay
DMH
purity
not
reported
137100
(
1982)
acceptable
No
evidence
of
a
mutagenic
response
Page
20
of
57
Guideline
No./
Study
Type/
Substance
Purity
MRID
No.
(
year)/
Classification/
Doses
Results
Gene
Mutation
870.5300
In
vitro
Mammalian
Cell
Assay
EMH
purity
not
reported
137089
(
1982)
acceptable
S9­:
751,
1001,
1335,
1780,
2373,
3164,
4219,
5000,
5625,
7500
µ
g/
mL
S9+:
563,
751,
1001,
1780,
2373,
3164,
4219,
5625,
7500,
10,000
µ
g/
mL
No
evidence
of
genotoxic
effects
Gene
Mutation
870.5300
In
vitro
Mammalian
Cell
Assay
DMH
purity
not
reported
132165
(
1983)
acceptable
S9­:
563,
1001,
1335,
1780,
2373,
3164,
4219,
5625,
7500,
or
10,000

g/
mL.
S9+:
751,
1001,
1335,
1780,
2373,
3164,
4219,
5625,
7500,
or
10,000

g/
mL.
No
evidence
of
a
genotoxic
response
Cytogenetics
870.5375
In
vitro
Chromosome
Aberration
Assay
DMH
purity
97.0%
164037
(
265457)
(
1986)
acceptable
200,
500,
1000,
2000

g/
mL
No
cytotoxic
or
clastogenic
effects
observed
Cytogenetics
870.5375
In
vitro
Chromosome
Aberration
Assay
3DEMH
purity
not
reported
40348201
(
1987)
acceptable
S9­:
8,
15,
30,
or
60
µ
g/
ml
S9+:
15,
30,
60,
or
120
µ
g/
ml
No
evidence
of
structural
chromosomal
aberration
Cytogenetics
870.5375
In
vitro
Chromosome
Aberration
Assay
EMH
purity
not
reported
137096
(
1982)
acceptable
5739.80,
7653.06,
or
10204.08
µ
g/
ml
A
2­
fold
or
greater
increase
in
the
percentage
of
cells
with
structural
chromosomal
aberrations,
excluding
gaps,
was
seen
at
two
non­
consecutive
doses
after
treatment
in
the
presence
of
S9­
mix.
No
dose
response
was
evident.
Results
from
the
treatments
in
the
absence
of
S9­
mix
were
negative
at
all
doses.
No
increase
in
polyploid
cells
was
observed
in
treated
or
in
positive
control
cultures.
Page
21
of
57
Guideline
No./
Study
Type/
Substance
Purity
MRID
No.
(
year)/
Classification/
Doses
Results
Cytogenetics
870.5375
In
vitro
Chromosome
Aberration
Assay
DMH
purity
not
reported
137101
(
1982)
acceptable
S9­:
11250,
15000,
or
20,000
µ
g/
ml
S9+:
8457.5,
11250,
or
15000
µ
g/
ml.
No
evidence
of
structural
chromosomal
aberration
Cytogenetics
870.5375
In
vitro
Chromosome
Aberration
Assay
DMH
purity
not
reported
MRID:
N/
A
TRID:
470264004
(
1986)
acceptable
80,
400,
or
800
µ
g/
ml
No
evidence
of
structural
chromosomal
aberration
Cytogenetics
870.5375
In
vitro
Chromosome
Aberration
Assay
DMH
purity
100%
MRID:
N/
A
TRID:
470264005
(
1986)
acceptable
10,
20,
40,
80,
160,
320,
640,
1280,
2560,
5120,
10240,
or
20480
µ
g/
ml
No
evidence
of
structural
chromosomal
aberration
Other
Effects
870.5550
Unscheduled
DNA
Synthesis
Assay
in
Rat
Hepatocytes
DMH
purity
97.0%
164038
(
265457)
(
1986)
acceptable
100,
300,
600,
1000,
3000,
6000,
10000

g/
mL
No
evidence
of
a
genotoxic
response
Other
Effects
870.5550
Unscheduled
DNA
Synthesis
Assay
in
Rat
Hepatocytes
EMH
purity
not
reported
137097
(
1982)
acceptable
0.1,
0.5,
1,
5,
10,
or
15
mg/
mL
No
evidence
of
a
genotoxic
response
Other
Effects
870.5550Unscheduled
DNA
Synthesis
Assay
in
Rat
Hepatocytes
DMH
purity
not
reported
132166
(
1982)
acceptable
0.001,
0.01,
0.1,
1,
10,
or
20
mg/
ml
No
evidence
of
a
genotoxic
response
Page
22
of
57
Guideline
No./
Study
Type/
Substance
Purity
MRID
No.
(
year)/
Classification/
Doses
Results
Neurotoxicity
870.6300
Developmental
neurotoxicity
Not
required
Metabolism/
Pharmacokinetics
870.7485
Metabolism
and
pharmacokinetics
DMH
purity
radiolabeled
98.8%
nonradiolabeled
99.5%
42173901/
42123802
(
1991)
acceptable
100,
1000
mg/
kg
DMH
was
rapidly
absorbed
and
excreted,
primarily
in
the
urine
(>
89%).
There
was
little
accumulation
in
the
tissues.

1
DMH=
dimethylhydantoin
2
EMH=
ethylmethylhydantoin
3
DEMH=
dichloroethylmethylhydantoin
Page
23
of
57
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."

There
are
no
data
gaps
for
reproductive
or
developmental
toxicity
testing
of
5,5­
dimethylhydantoin.
Evidence
of
increased
sensitivity
was
observed
in
a
developmental
toxicity
study
in
rabbits
(
MRID
#
42413101).
In
this
study,
treatment­
related
anomalies
(
increased
incidence
of
adactyly
at
1000
mg/
kg/
day;
increased
litter
and
fetal
incidence
of
27th
presacral
vertebrae
at
500
and
1000
mg/
kg/
day)
were
observed
in
fetal
rabbits
in
the
absence
of
maternal
toxicity.
It
has
been
stated
recently
that
the
presence
of
27th
presacral
vertebrae
in
rabbits
may
not
be
considered
an
effect
with
an
adverse
developmental
outcome
("
Additional
Comments
on
the
Revised
Report
of
the
Hazard
Identification
Assessment
Review
Committee
for
5,5­
Dimethylhydantoin,"
Toxicology/
Regulatory
Services,
June
6,
2003).
The
available
data
from
the
rabbit
study,
however,
do
indicate
a
clear
effect
level
for
offspring
and
a
clear
no­
effect
level,
and
these
effects
occur
in
the
absence
of
maternal
toxicity.

In
the
reproductive
toxicity
study
in
rats
(
MRID
43290601),
pup
effects
(
decreased
body
weight
and
weight
gain)
were
observed
during
days
7­
21
of
lactation
in
the
absence
of
any
parental
toxicity.
However,
the
HIARC
considered
this
effect
not
indicative
of
susceptibility,
based
upon
the
very
high
dose
level
at
which
the
effect
occurred
(
1322
mg/
kg/
day),
the
minimal
nature
of
the
effect,
and
the
likelihood
that
the
effect
was
due
to
a
greater
dose
received
by
pups
from
ingestion
of
both
milk
and
feed
during
the
lactational
period.
Overall,
from
examination
of
the
effects
of
DMH
in
the
standard
developmental
and
reproductive
toxicity
testing
data
submitted
to
the
Agency,
the
HIARC
concluded
that
there
was
some
evidence
for
increased
susceptibility,
but
based
on
the
selection
of
a
developmental
endpoint
for
dietary
risk
assessment,
an
additional
safety
factor
to
address
FQPA
concerns
is
not
necessary,
as
the
developmental
endpoint
is
sufficiently
protective
of
effects
that
may
occur
in
infants
and
children
from
exposure
to
dimethylhydantoin.

3.3
Dose­
Response
Assessment
On
July
25,
2000
,
the
Health
Effects
Division
(
HED)
Hazard
Identification
Assessment
Review
Committee
(
HIARC)
reviewed
the
recommendations
of
the
toxicology
reviewer
for
5,5­
dimethylhydantoin
with
regard
to
the
acute
and
chronic
Reference
Doses
(
RfDs)
and
the
toxicological
endpoint
selection
for
use
as
appropriate
in
occupational/
residential
exposure
risk
Page
24
of
57
assessments.
The
potential
for
increased
susceptibility
of
infants
and
children
from
exposure
to
5,5­
dimethylhydantoin
(
a
chemical
representative
of
hydantoin
toxicity)
was
also
evaluated
as
required
by
the
Food
Quality
Protection
Act
(
FQPA)
of
1996.
Endpoints
were
established
for
the
dihalodialklhydantoins
and
a
report
issued.
Table
4
summarizes
the
findings
of
the
studies
reviewed.

Table
4.
Summary
of
Toxicological
Dose
and
Endpoints
for
the
hydantoins
for
Use
in
Human
Risk
Assessment1
Exposure
Scenario
Dose
Used
in
Risk
Assessment,
UF
FQPA
SF
and
Endpoint
for
Risk
Assessment
Study
and
Toxicological
Effects
Acute
Dietary
females
13­
50
years
of
age
NOAEL
=
100
mg/
kg/
day
UF
=
100
Acute
RfD
=
1
mg/
kg
FQPA
SF
=
1
aPAD
=
acute
RfD
FQPA
SF
=
1
mg/
kg/
day
developmental
toxicity
­
rabbit
developmental
LOAEL
=
500
mg/
kg/
day
based
on
skeletal
variations.
(
MRID
42413101)

Chronic
Dietarya
all
populations
NOAEL=
300
mg/
kg/
day
UF
=
100
Chronic
RfD
(
gen
Pop.)
=
3
mg/
kg/
day
FQPA
SF
=
1
cPAD
=
chr
RfD
FQPA
SF
=
3
mg/
kg/
day
chronic
toxicity/
carcinogenicity
­
rats
LOAEL
=
1000
mg/
kg/
day
based
on
decreased
body
weight/
weight
gain
and
lymph
node
hyperplasia.
(
MRID
43397702)

Chronic
Dietarya
females
13­
50
NOAEL=
100
mg/
kg/
day
UF
=
100
Chronic
RfD
(
females
13­
50)
=
1
mg/
kg/
day
FQPA
SF
=
1
cPAD
=
chr
RfD
FQPA
SF
=
1
mg/
kg/
day
developmental
toxicity
­
rabbit
developmental
LOAEL
=
500
mg/
kg/
day
based
on
skeletal
variations.
(
MRID
42413101)

Short­
Term
Oral
(
1­
30
days)

(
Incidental)
oral
study
NOAEL=
500
mg/
kg/
day
UF
=
100
Residential,
includes
the
1x
FQPA
SF
developmental
toxicity
­
rabbit
maternal
LOAEL
=
1000
mg/
kg/
day
based
on
decreased
body
weight
gain
in
maternal
rabbits.
(
MRID
42413101)

Intermediate­
Term
Oral
(
1
to
6
months)

(
Incidental)
oral
study
NOAEL=
300
mg/
kg/
day
UF
=
100
Residential,
includes
the
1x
FQPA
SF
subchronic
oral
toxicity
­
rat
LOAEL
=
1000
mg/
kg/
day
based
on
decreased
body
weight
and
liver
weight.
(
MRID
42009201)
Page
25
of
57
Exposure
Scenario
Dose
Used
in
Risk
Assessment,
UF
FQPA
SF
and
Endpoint
for
Risk
Assessment
Study
and
Toxicological
Effects
Dermal­
all
time
periods
Short­,(
1­
30
days),
Intermediate­,
(
1
to
6
months),
Long­
term
(>
6
months)
(
Occupational/
Residential)
dermal
study
NOAEL=
390
mg/
kg/
day
(
HDT)
UF
=
100
for
all
populations
MOE
=
100
(
Occupational)

Residential,
includes
the
1x
FQPA
SF
subchronic
dermal
toxicity
­
rats
No
systemic
toxicity
at
the
highest
dose
tested
(
MRID
43173901)

Short­
Term
Inhalation
(
1­
7
days)

(
Occupational/
Residential)
Oral
NOAEL=
100b
mg/
kg/
day
(
inhalation
absorption
rate
=
100%)
UF
=
100
for
all
populations
Residential,
includes
the
1x
FQPA
SF
developmental
toxicity
­
rabbit
developmental
LOAEL
=
500
mg/
kg/
day
based
on
skeletal
effects
in
offspring.
(
MRID
42413101)

1
UF
=
uncertainty
factor,
FQPA
SF
=
FQPA
safety
factor,
NOAEL
=
no
observed
adverse
effect
level,
LOAEL
=
lowest
observed
adverse
effect
level,
PAD
=
population
adjusted
dose
(
a
=
acute,
c
=
chronic)
RfD
=
reference
dose,
MOE
=
margin
of
exposure
AThe
HIARC
selected
separate
chronic
RfDs
for
females,
ages
13­
50,
and
the
general
population.
A
separate
endpoint
for
the
general
population
was
selected
because
this
was
an
unusual
case
where
the
developmental
toxicity
NOAEL
was
lower
than
the
NOAEL
from
the
chronic
toxicity
studies.
The
chronic
RfD
for
the
general
population
provides
a
more
appropriate
endpoint
for
individuals
other
than
females
Page
26
of
57
3.4
Endocrine
Disruption
The
Agency
is
required
under
the
Federal
Food,
Drug
and
Cosmetic
Act
(
FFDCA),
as
amended
by
FQPA,
to
develop
a
screening
program
to
determine
whether
certain
substances
(
including
all
pesticide
active
and
other
ingredients)
"
may
have
an
effect
in
humans
that
is
similar
to
an
effect
produced
by
a
naturally
occurring
estrogen,
or
other
such
endocrine
effects
as
the
Administrator
may
designate."
Following
the
recommendations
of
its
Endocrine
Disruptor
Screening
and
Testing
Advisory
Committee
(
EDSTAC),
EPA
determined
that
there
was
scientific
bases
for
including,
as
part
of
the
program,
the
androgen
and
thyroid
hormone
systems,
in
addition
to
the
estrogen
hormone
system.
EPA
also
adopted
EDSTAC's
recommendation
that
the
Program
include
evaluations
of
potential
effects
in
wildlife.
For
pesticide
chemicals,
EPA
will
use
FIFRA
and,
to
the
extent
that
effects
in
wildlife
may
help
determine
whether
a
substance
may
have
an
effect
in
humans,
FFDCA
authority
to
require
the
wildlife
evaluations.
As
the
science
develops
and
resources
allow,
screening
of
additional
hormone
systems
may
be
added
to
the
Endocrine
Disruptor
Screening
Program
(
EDSP).

4.0
EXPOSURE
ASSESSMENT
AND
CHARACTERIZATION
4.1
Summary
of
Registered
Uses
Halohydantoin
is
an
antimicrobial
used
to
control
slime
formation
in
water
systems.
Registered
use
sites
include
cooling
water
systems,
paper
and
paperboard
process
water,
wastewater
treatment,
use
as
an
in­
tank
toilet
bowl
sanitizer,
and
use
in
swimming
pools.
Maximum
application
rates
range
from
0.000098
lb
ai/
gallon
for
transportation
cleaning
water
systems
and
up
to
0.00122
lb
ai/
gallon
for
spas.
Dihalodialkylhydantoin
is
formulated
in
the
following
forms:
tablet,
pellet,
briquette,
granular,
ready­
to­
use
solution,
wettable
powder,
soluble
concentrate,
and
gel.
Based
on
examination
of
the
labels,
all
formulations
are
solid
formulations
(
as
opposed
to
liquid
formulations).
Despite
the
large
variety
of
uses,
the
application
of
dihalodialkylhydantoin
is
limited,
in
general,
to
two
methods:
placement
of
tablets/
ready­
to­
use
solutions,
and
pouring
of
powders/
granules.
The
application
rates
used
in
the
assessment
are
based
on
the
maximum
stated
application
rates
on
labels.
The
scenarios
considered
in
the
risk
assessment
are
shown
in
Table
5.
These
scenarios
were
selected
based
on
examination
of
product
labels
describing
uses
for
the
product.
Most
of
the
scenarios
fall
under
the
"
industrial
premises
and
water
systems"
category.
Page
27
of
57
Table
5.
Dihalodialkylhydantoins
Scenarios
Use
Site
Category
Scenario
(
Representing
high
end
exposures,
but
not
inclusive
of
all
uses)

Material
Preservative
°
Household
cleaning
products
°
Paints
Industrial
Premises
and
Water
Systems
(
Industrial)
°
Placing
the
dihalodialkylhydantoin
tablets/
pellets
into
cooling
and
process
water
systems
°
Pouring
dihalodialkylhydantoin
granules/
powders
into
a
feeder
for
cooling
and
process
water
systems
°
Process
water
systems
includes:
recirculating
cooling
water,
oncethrough
cooling
water,
sewage
systems,
pulp
and
paper
process
water,
photo
processing
water,
air
washers,
evaporative
coolers,
and
cannery
water
Commercial,
Institutional
and
Industrial
Premises
and
Equipment
(
Commercial/
Institutiona
l
Premises)
°
Placing
dihalodialkylhydantoin
tablets
into
air
conditioner/
humidifier
drip
pans
°
Placing
dihalodialkylhydantoin
tablets
in
ornamental
fountains
°
Placing
dihalodialkylhydantoin
tablets
in
transportation
cleaning
water
systems
Swimming
Pools
°
Placing
or
pouring
dihalodialkylhydantoin
tablets/
granules
in
swimming
pools
and
hot
tubs
Residential
and
Public
Access
Premises
(
Residential)
°
Handling
of
liquid
general
purpose
cleaner
°
Placing
dihalodialkylhydantoin
tablets
into
toilet
tank
°
Using
brush/
roller/
airless
sprayer
to
apply
paint
to
house
°
Toddler
exposure
to
residues
of
carpet
shampoo
°
Toddler
and
adult
exposure
to
treated
clothing
Agricultural
Premises
and
Equipment
°
Pouring
dihalodialkylhydantoin
granules
vehicle
and
foot
baths
at
the
entrances
to
greenhouses
Aquatic
Areas
°
Placing/
pouring
dihalodialkylhydantoin
tablets/
granules
chemigation/
irrigation
systems
4.2
Dietary
Exposure/
Risk
Pathway
4.2.1
Residue
Profile
The
Agency
has
carried
out
the
dietary
exposure
and
risk
assessment
for
use
of
Halohydantoins
as
a
slimicide
in
food
contact
paper
and
paperboard,
and
for
use
as
a
preservative
in
inorganic
slurries
which
are
used
as
fillers
for
food
contact
paper
and
paperboard.
No
residue
chemistry
data
were
submitted
by
the
registrants,
nor
were
any
asked
for
by
the
Agency.
The
Agency
has
used
available
methods
to
estimate
dihalodialkylhydantoin
residues
on
food
due
to
Page
28
of
57
migration
of
these
chemicals
or
their
breakdown
products,
when
these
substances
come
into
contact
with
food­
contact
paper
and
paperboard.
In
this
regard,
the
Food
and
Drug
Administration
has
developed
guidelines
to
estimate
the
residues
of
pesticides
used
as
slimicides
on
food
contact
paper
and
paperboard.
The
Agency
has
decided
to
use
FDA
methodology
to
estimate
the
residues
of
such
chemicals
and/
or
their
breakdown
products
on
food
items
and
also
to
determine
the
Estimated
Daily
Intake
(
EDI)
of
these
pesticides.

4.2.2
Dietary
Exposure
and
Risk
EPA
used
two
methods
to
calculate
Dietary
exposure
to
adult
populations.
In
the
first
method,
the
following
assumptions
were
made:

°
Food
contact
surface
could
be
a
one
time
use/
day
or
repeat
use
material/
day;
°
The
amount
of
food
that
comes
into
contact
with
the
treated
paper
is
based
on
an
FDA
default
value;
°
All
of
the
active
material
present
in
the
paper
migrates
into
the
food.

In
the
second
(
alternative)
method,
additional
consideration
is
made
as
to
the
type
of
food
that
is
being
contained
in
the
treated
paper,
and
factors
such
as
the
quantity
of
active
ingredient
in
the
paper
are
not
considered.

The
concentration
of
halohydantoins
in
the
paper
slurry
was
calculated
assuming
that
the
chemical
was
used
both
as
a
slimicide
and
as
a
preservative
in
paper.
Although
two
types
of
use
involve
different
moities
(
dimethylhydantoin
for
slimicide,
methylol
dimethylhydantoin
for
preservative),
the
concentrations
were
summed
together
to
determine
a
total
concentration
of
halohydantoins
in
the
slurry.
The
EDI
was
then
calculated
based
on
this
concentration
for
both
adults
and
children.
The
results
of
the
calculations
are
shown
in
Tables
6
and
7.
Acute
dietary
exposures
were
calculated
only
for
the
adult
female
population,
as
the
acute
dietary
endpoint
selected
was
for
females
between
13­
50
years.
The
acute
dietary
exposure
for
an
adult
female
is
0.046%
of
the
acute
PAD.
The
highest
chronic
exposure
occurred
in
adult
females
(
0.0153%
of
the
chronic
PAD).

Table
6.
Summary
of
Dietary
Exposure
and
Risk
for
Halohydantoins
(
1st
Method)

Population
Subgroup
EDI
mg/
day
Acute
Dietary
Chronic
Dietary
Dietary
Exposurea
(
mg/
kg/
day)
%
aPAD
b
Dietary
Exposure
(
mg/
kg/
day)
a
%
cPAD
b
Adult
Male
0.0276
­­
­­
3.94x10­
4
0.0131
Adult
Female
0.0276
4.60x10­
4
0.046
4.60x10­
4
0.0153
Children
0.0138
­­
­­
1.38x10­
3
0.046
a­­
acute
and
chronic
exposure
analysis
based
on
daily
consumption
of
0.00276
mg/
person/
day
for
adults
and
body
weights
of
70
kg
and
60
kg
for
males
and
females,
respectively.
For
infants/
children,
exposure
based
on
daily
consumption
of
0.0138
mg/
person/
day;
and
a
10
kg
body
weight.
b­­%
PAD
=
dietary
exposure
(
mg/
kg/
day)
*
100
/
aPAD
or
cPAD,
where
aPAD
for
females
between
13­
50
years
of
age
=
1.0
Page
29
of
57
mg/
kg/
day
and
cPAD
for
the
general
population
=
3.0
mg/
kg/
day
Table
7.
Summary
of
Dietary
Exposure
and
Risk
for
Halohydantoins
(
2nd
Method)

Population
Subgroup
EDI
mg/
day
Acute
Dietary
Chronic
Dietary
Dietary
Exposurea
(
mg/
kg/
day)
%
aPAD
b
Dietary
Exposure
(
mg/
kg/
day)
a
%
cPAD
b
Adult
Male
0.96
­­
­­
0.0137
0.457
Adult
Female
0.96
0.016
1.6
0.016
0.533
Children
0.48
­­
­­
0.048
1.6
a­­
acute
and
chronic
exposure
analysis
based
on
daily
consumption
of
0.96
mg/
person/
day
for
adults
and
body
weights
of
70
kg
and
60
kg
for
males
and
females,
respectively.
For
infants/
children,
exposure
based
on
daily
consumption
of
0.48
mg/
person/
day;
and
a
10
kg
body
weight.
b­­%
PAD
=
dietary
exposure
(
mg/
kg/
day)
*
100
/
aPAD
or
cPAD,
where
aPAD
for
females
between
13­
50
years
of
age
=
1.0
mg/
kg/
day
and
cPAD
for
the
general
population
=
3.0
mg/
kg/
day
4.3
Water
Exposure/
Risk
Pathway
AD
has
considered
the
registered
uses
of
dihalodialkylhydantoin
and
the
available
data
on
persistence
and
mobility.
The
Agency
currently
lacks
sufficient
water­
related
exposure
data
from
monitoring
to
complete
a
quantitative
drinking
water
exposure
analysis
and
risk
assessment
for
dihalodialkylhydantoin.
Therefore,
the
Agency
is
presently
relying
on
predicted
environmental
concentrations
(
PECs)
of
pesticides
in
surface
water
to
estimate
drinking
water
exposures
to
dihalodialkylhydantoin.

Use
of
the
pesticide
in
industrial
water
systems
is
expected
to
impact
surface
and
ground
water
resources.
Out
of
all
the
industrial
water
systems
for
which
the
pesticide
is
used,
the
oncethrough
cooling
water
system
can
be
expected
to
have
the
greatest
impact
on
the
water,
since
the
scenario
has
the
greatest
quantity
of
effluent
being
produced
and
has
the
greatest
chance
of
bacterial
fouling
and
need
for
pesticide.
The
PDM4
Model
was
used
to
estimate
exposure
from
once­
through
cooling
tower
uses.
The
details
of
this
model
are
found
in
the
Environmental
Modeling
Chapter
of
this
document.
A
low­
flow
power
plant
(
100
+
10
million
gallons
per
day)
was
used
as
the
scenario
providing
the
maximum
concentrations
of
DMH
in
the
receiving
water,
e.
g.,
the
"
worst
case"
scenario.
Actual
concentrations
in
receiving
waters
are
likely
lower,
and
will
likely
not
show
an
increasing
trend
as
indicated
by
the
model,
due
to
higher
flow
rates
and
possible
degradation/
dissipation
of
DMH
by
mechanisms
other
than
hydrolysis.

A
drinking
water
level
of
comparison
(
DWLOC)
is
the
concentration
of
a
pesticide
in
drinking
water
that
would
result
in
risk
estimates
below
AD's
level
of
concern,
when
considering
total
aggregate
exposure
to
that
pesticide
from
food,
water,
and
residential
uses.
AD
uses
DWLOCs
in
the
risk
assessment
process
as
a
surrogate
measure
of
potential
exposure
associated
with
pesticide
exposure
through
drinking
water.
DWLOC
values
are
not
regulatory
standards
for
drinking
water;
however,
they
do
have
an
indirect
regulatory
impact
through
aggregate
exposure
and
risk
assessment.
In
the
absences
of
monitoring
data
for
a
pesticide,
the
DWLOC
is
used
as
a
point
of
comparison
against
the
conservative
PEC
provided
by
computer
modeling.
A
DWLOC
Page
30
of
57
may
vary
with
drinking
water
consumption
patterns
and
body
weight
for
specific
subpopulations.

AD
back­
calculated
DWLOCs
by
a
two­
step
process:
exposure
[
food+
(
if
applicable)
residential
exposure]
is
subtracted
from
the
PAD
to
obtain
the
maximum
exposure
allowed
in
drinking
water;
DWLOCs
are
then
calculated
using
that
value
and
default
body
weight
and
drinking
water
consumption
figures.
In
assessing
human
health
risk,
DWLOCs
are
compared
to
the
EEC.
When
the
EEC
is
greater
than
the
DWLOCs,
AD
considers
the
aggregate
risk
to
exceed
the
Agency's
level
of
concern.

4.4
Residential
Exposure/
Risk
Pathway
Details
of
the
residential
exposure
and
risk
assessment
can
be
found
in
the
Occupational
and
Residential
Exposure
(
ORE)
Chapter.
A
summary
of
the
residential
assessment
is
presented
below.

4.4.1
Residential
Handler
Scenarios
Dihalodialkylhydantoin
may
be
added
as
a
material
preservative
to
control
bacteria
and
fungi
in
residential­
use
products.
A
number
of
such
products
have
been
identified,
including
household
cleaning
products,
paints,
adhesives,
and
deodorizers.
It
is
also
used
in
pools
and
spas.
For
the
purposes
of
this
screening­
level
assessment,
handler
scenarios
have
been
assessed
for
residential
uses
that
represent
high
end
exposures
for
the
wide
variety
of
products.
Therefore,
not
all
products
are
assessed
individually.
Table
8
presents
the
handler
scenarios
considered
to
represent
the
high
end
of
exposure
for
the
residential
assessment.
Household
cleaning
products
and
carpet
shampoo
have
been
grouped
together.
Of
these
products,
household
cleaning
products,
which
should
yield
the
greatest
amount
of
handler
exposure
to
the
chemical,
was
selected
for
analysis.
In­
tank
toilet
tablets,
which
are
placed
into
toilet
tanks,
differ
from
the
other
household
cleaning
products
in
that
they
are
not
liquid.
These
tablets
were
evaluated
in
a
separate
scenario.
Adhesives,
caulks,
and
paints
have
also
been
grouped
together
for
evaluation.
Of
these
types
of
uses,
the
painting
scenario,
which
should
yield
the
greatest
amount
of
handler
exposure
to
the
chemical,
was
selected
for
analysis.
Finally,
the
pool/
spa
and
air
conditioner
drip
pan
uses
are
represented
by
the
application
to
residential
(
i.
e.,
backyard)
swimming
pools
and
spas.

Table
8.
Residential
Handler
Scenarios
Handler
Scenario
Typical
Products
Represented
(
but
not
limited
to)

Handling
of
liquid
general
purpose
cleaner
Household
cleaning
products,
carpet
shampoo,
deodorizer
Solid
placement
of
in­
tank
toilet
cleaner
In­
tank
toilet
tablet
Painting
of
a
house
using
brush,
roller,
or
airless
sprayer
Paint,
adhesives,
caulk
Page
31
of
57
Solid
placement
into
swimming
pools
&
spas
Pools/
spas
and
air
conditioner
drip
pans
4.4.1.1
General
Purpose
Cleaner
EPA
has
estimated
dermal
and
inhalation
exposure
while
wiping
and
mopping
to
represent
the
material
preservative
use
for
household
cleaning
products.
The
following
two
scenarios
were
considered
for
residential
handlers
of
household
cleaning
products
preserved
with
halohydantoins:

°
Use
of
household
cleaning
products
by
wiping
on
hard
non­
porous
surfaces,
and
°
Use
of
household
cleaning
products
by
mopping
on
floors.

An
application
rate
could
not
be
determined
from
the
labels.
Therefore,
the
maximum
concentration
listed
on
the
label
(
i.
e.,
EPA
Reg.
No.
6836­
271)
is
used
along
with
assumptions
on
the
amount
of
cleaning
product
diluted
in
water.
EPA
Reg.
No.
6836­
271
indicates
that
the
product,
Dantogard
Plus
Liquid,
can
be
added
to
household
cleaning
products
as
a
preservative
at
a
rate
of
0.2
to
2.0
percent
by
weight.
Given
that
EPA
Reg.
No.
6836­
271
contains
52.4
percent
active
ingredient
associated
with
this
RED
case
(
i.
e.,
26.9%
1,3­
Bis(
hydroxymethyl)­
5,5­
dimethylhydantoin
plus
25.5%
1­(
Hydroxymethyl)­
5,5­
dimethylhydantoin)
and
an
assumption
that
the
product
has
the
density
of
water,
yields
an
estimate
of
0.084
lb
ai/
gallon
of
a
generic
household
cleaning
product
(
i.
e.,
8
lb/
gal
cleaner
x
0.02
Dantogard
x
0.524
ai).
Additionally,
it
is
assumed
that
4
ounces
of
a
generic
household
cleaning
product
is
mixed
per
gallon
of
water
or
0.0026
lb
ai/
gallon
of
diluted
cleaning
solution
for
both
mopping
and
wiping
(
i.
e.,
0.084
lb
ai/
gal
cleaning
product
x
(
1/
128
ounce
per
gallon
conversion)
x
4
ounces
cleaning
product
per
gallon
water).

CMA
data
were
used
to
determine
the
unit
dermal
and
inhalation
exposures.
The
no
gloved
CMA
unit
exposure
data
for
wiping
and
mopping
were
used
to
determine
the
dermal
and
inhalation
exposure.
It
was
assumed
that
0.5
liter
(
0.132
gallons)
is
used
for
wiping
and
1
gallon
is
used
for
mopping.

The
results
of
the
MOE
analysis
for
these
scenarios
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
inhalation
endpoint
used
in
the
assessment
represents
only
the
short­
term
duration.
The
calculated
dermal
and
inhalation
MOEs
are
not
of
concern
for
any
of
the
scenarios
(
MOE
greater
than
10,000
for
all
scenarios).
However,
as
formaldehyde
is
a
metabolite
of
halohydantoins,
there
may
be
risk
associated
with
this
exposure,
particularly
for
use
of
products
that
produce
a
greater
chance
of
inhalation
exposure
to
formaldehyde,
such
as
air
fresheners.
Risks
associated
with
formaldehyde
will
be
assessed
at
a
later
date.
Page
32
of
57
Table
9.
Calculation
of
Short­
term
Dermal
and
Inhalation
MOE
for
Residential
Handlers
of
Cleaning
Products
a
Exposure
Scenario
Method
of
Applicati
on
Dermal
Unit
Exposure
(
mg/
lb
ai)
b
Inhalatio
n
Unit
Exposure
(
mg/
lb
ai)
c
Appl.
Rate
d
(
lb
a.
i./
gal)
Amount
Treated
Dermal
Dose
(
mg/
kg/
day)
f
Dermal
MOE
g
Inhalation
Dose
(
mg/
kg/
day
)
h
Inhalatio
n
MOE
i
Household
Cleaning
Products
Wipes
2870
(
CMA
no
glove)
67.3
(
CMA)
0.0026
0.5
liter
of
product
(
0.13
gal)
0.014
28,000
0.00033
300,000
Mopping
71.6
2.38
0.0026
1
gallon
0.0053
73,000
0.00018
570,000
aMOEs
rounded
to
2
significant
figures.
bDermal
unit
exposures
are
from
CMA.
cInhalation
unit
exposures
are
from
CMA.
dApplication
rates
are
based
on
EPA
Reg.
No.
6836­
271.
fDermal
dose
(
mg/
kg/
day)
=
[
unit
exposure
(
mg/
lb
ai)
*
Appl.
rate
(
lb
ai/
gallon)
*
gallons
handled
/
Body
weight
(
70
kg).
gDermal
MOE
=
NOAEL
(
mg/
kg/
day)
/
Daily
Dose
[
Where
short­
term
dermal
NOAEL
=
390
mg/
kg/
day].
Target
MOE
is
100.
hInhalation
dose
(
mg/
kg/
day)
=
[
unit
exposure
(
mg/
lb
ai)
*
max
appl
rate
(
lb
ai/
gal)
*
gallons
handled
*
1
inhalation
absorption]
/
Body
weight
(
70
kg).
i
Inhalation
MOE
=
NOAEL
(
mg/
kg/
day)
/
Daily
Dose
[
where
short­
term
inhalation
NOAEL
is
100
mg/
kg/
day].
Target
MOE
is
100.

4.4.1.2
In­
Tank
Toilet
Cleaner
All
products
available
for
use
of
dihalodialkylhydantoin
as
a
toilet
cleaner
are
in
tablet
form.
It
has
been
estimated,
based
on
packaging
size
and
the
number
of
tablets
per
package,
that
the
size
of
a
single
tablet
is
0.08
pounds
(
98
percent
ai).
It
has
been
assumed
that
a
single
individual
maintains
a
house
containing
three
toilets.
In
general,
the
clothing
attire
worn
by
homeowners
during
application
is
assumed
to
be
short
pants
and
short­
sleeved
shirt.
The
unit
exposure
values,
which
are
the
same
as
those
used
for
previous
solid
place
scenarios,
are
taken
from
CMA
data.
However,
the
"
ungloved"
scenario
solid
place
unit
exposure
value
from
the
CMA
data
is
for
workers
wearing
long­
sleeved
shirts
and
long
pants.
Lacking
better
data
for
this
scenario,
this
value
has
been
used.
The
estimated
short­
term
dermal
and
inhalation
MOEs
for
this
task
are
11,000
and
110,000
respectively.
Therefore,
the
risks
are
not
of
concern
(
i.
e.,
MOEs
are
greater
than
the
target
MOE
value
of
100).
See
ORE
Chapter
for
a
more
detailed
review.

4.4.1.3
Painting
Two
painting
scenarios
have
been
analyzed
in
this
assessment:
a
homeowner
using
a
brush
to
paint
walls
in
a
house,
and
a
homeowner
using
an
airless
sprayer
to
paint
a
house.
The
exposures
associated
with
both
of
these
painting
scenarios
were
determined
using
procedures
described
in
the
Residential
SOPs
(
USEPA,
2000b).
In
following
these
procedures,
a
number
of
assumptions
have
been
made.

°
For
paints
used
with
a
brush,
the
amount
of
paint
used
is
2
gallons
per
day.
This
is
based
on
a
90th
percentile
value
of
8
gallons
of
latex
paint
used
per
year
divided
by
the
mean
frequency
of
4
painting
events
per
year
(
USEPA,
1997).
Page
33
of
57
°
For
painting
with
an
airless
sprayer,
a
homeowner
is
assumed
to
use
three
5­
gallon
cans
of
ready­
to­
use
product
(
i.
e.,
15
gallons).
This
is
based
on
a
coverage
rate
of
200
ft2/
gallon
and
a
house
size
of
40x30x20
ft
(
surface
area
of
2,800
ft2)
(
USEPA,
2000b).
°
Maximum
weight
fraction
of
ai
in
product
is
0.01048.
°
Surrogate
data
from
PHED
were
used
for
the
dermal
and
inhalation
unit
exposures.
°
The
density
of
the
paint
was
assumed
to
be
1.24
g/
mL.

The
short­
term
dermal
and
inhalation
MOEs
calculated
for
use
of
a
brush
were
570
and
120,000,
respectively.
The
short­
term
dermal
and
inhalation
MOEs
calculated
for
use
of
an
airless
sprayer
were
220
and
5,400,
respectively.
All
MOEs
calculated
for
painting
scenarios
are
greater
than
the
target
MOE
of
100
and
are
not
of
concern.
See
ORE
Chapter
for
a
more
detailed
review.

4.4.1.4
Swimming
Pool
and
Spa
Products
available
for
use
of
dihalodialkylhydantoin
in
pools
and
spas
are
formulated
as
solids
(
assessment
of
solids
include
"
place"
and
"
pour"
as
defined
by
the
CMA
exposure
data).
It
has
been
estimated
that
a
large
residential
swimming
pool
has
a
volume
of
20,000
gallons
and
a
large
spa
contains
~
1,000
gallons.
Application
rates
for
pools
and
spas
are
180
grams/
10,000
gallons
and
85
grams/
150
gallons,
respectively.
In
general,
the
clothing
attire
worn
by
homeowners
during
application
is
assumed
to
be
short
pants
and
short­
sleeved
shirt.
The
unit
exposure
values,
which
are
the
same
as
those
used
for
previous
solid
place
scenarios,
are
taken
from
CMA
data.
However,
the
"
ungloved"
scenario
from
the
CMA
data
is
for
workers
wearing
long­
sleeved
shirts
and
long
pants.
Lacking
better
data
for
this
scenario,
this
value
has
been
used.
The
estimated
short­
term
dermal
and
inhalation
MOEs
for
application
to
swimming
pools
are
460
to
3,200
(
solid
pour
and
solid
place)
and
220,000
to
6,500,000
(
solid
pour
and
solid
place)
respectively.
The
short­
term
dermal
and
inhalation
MOEs
for
application
to
spas
are
140
to
980
(
solid
pour
and
solid
place)
and
67,000
to
2,000,000
(
solid
pour
and
solid
place)
respectively.
All
of
the
estimated
MOEs
are
greater
than
the
target
MOE
value
of
100,
indicating
no
risks
of
concern.
The
results
of
the
residential
handlers
for
swimming
pools
and
spas
are
included
in
the
occupational
section
(
see
Table
15).
See
ORE
Chapter
for
a
more
detailed
review.

4.4.2
Residential
Postapplication
Exposure
For
the
purposes
of
this
screening
level
assessment,
postapplication
scenarios
have
been
developed
that
encompass
multiple
products
representing
the
high­
end
exposure
scenario
for
all
products
represented.
Table
16
presents
the
postapplication
scenarios
considered
in
this
assessment.
Three
scenarios
have
been
considered:
(
1)
exposure
to
residue
from
hard
floors
that
have
been
cleaned/
moped
with
a
general
cleaner
containing
dihalodialkylhydantoin,
(
2)
exposure
to
residue
on
clothing
that
has
been
treated
with
dihalodialkylhydantoin
during
textile
processing,
and
(
3)
exposure
to
swimmers
in
treated
pools.
For
this
screening­
level
assessment,
fabric
softeners
have
been
grouped
with
textile
processing
chemicals
for
calculating
exposure.
Page
34
of
57
4.4.2.1
Hard
Floor
Cleaner
There
is
the
potential
for
toddlers
playing
on
treated
floors
to
be
exposed
to
dihalodialkylhydantoin.
Due
to
limited
data,
the
following
assumptions
have
been
made
to
determine
toddler
exposure
playing
on
treated
hard
floors:

°
Toddlers
(
3
years
old)
are
used
to
represent
the
1
to
6
year
old
age
group.
°
As
a
conservative
estimate,
it
has
been
assumed
that
one
gallon
of
mopping
solution
can
treat
1000
ft2
of
floor
surface.
°
No
data
could
be
found
regarding
the
quantity
of
treatment
solution
residue
left
on
the
floor
after
treatment.
It
has
been
assumed
that
25%
of
the
solution
remains
after
the
final
mop.
°
No
leaching
data
were
available
that
could
be
used
to
estimate
the
residue
transfer
from
the
hard
surface
(
i.
e.,
floor).
Therefore,
the
Residential
SOP
estimate
of
10
percent
of
the
amount
on
the
floor
is
available
for
dermal
transfer.

The
short­
and
intermediate­
term
dermal
MOE
calculated
is
700,
which
is
above
the
target
MOE
of
100.
See
ORE
Chapter
for
a
more
detailed
review.

In
addition
to
the
dermal
exposure
from
toddlers
playing
on
treated
floors,
there
is
the
potential
for
incidental
oral
exposure
via
hand­
to­
mouth
activities.
Although
residential
floors
are
believed
to
be
washed/
moped
on
an
intermittent
basis,
facilities
such
as
day
care
centers
may
clean
the
floors
more
often.
Therefore,
both
the
short­
and
intermediate­
term
incidental
oral
endpoints
are
provided
to
assess
the
potential
risks.
Due
to
limited
data,
the
following
assumptions
from
the
Residential
SOPs
(
in
addition
to
the
assumptions
listed
above)
have
been
made
to
estimate
handto
mouth
exposures
for
toddlers
playing
on
treated
carpets:

°
The
surface
area
of
the
portion
of
the
hand­
to­
mouth
per
event
is
20
cm2;
°
The
number
of
hand­
to­
mouth
events
per
hour
is
20;
°
Exposure
time
is
4
hours/
day;
°
Saliva
extraction
efficiency
is
50
percent
Based
on
these
assumptio
ns,
the
potential
dose
rate
using
these
assumptions
is
0.07
mg/
kg/
day
resulting
in
a
hand­
to­
mouth
MOE
for
toddlers
of
7100
(
short­
term)
and
4300
(
intermediate­
term).

4.4.2.2
Clothing
Although
dihalodialkylhydantoin
has
been
listed
for
use
in
textile
processing,
it
is
unclear
in
what
capacity
the
chemical
is
to
be
used.
It
has
been
assumed,
for
this
risk
assessment,
that
the
chemical
is
impregnated
into
the
material
in
the
same
manner
as
a
dye
would
impregnated.
Data
on
which
these
calculations
could
be
based
were
generally
unavailable;
therefore,
a
number
of
conservative
assumptions
have
been
made:
Page
35
of
57
°
Toddlers
(
3
years
old)
are
used
to
represent
the
1
to
6
year
old
age
group
and
are
assumed
to
weigh
15
kg,
the
median
for
male
and
female
toddlers
(
USEPA,
2000b).
The
median
surface
area
for
a
3
year
old,
minus
the
head,
is
0.657
m2.
Median
values
for
body
weights
and
surface
areas
for
adults
have
been
used
(
70
kg
and
1.69
m2,
not
including
head
surface
area).
°
Based
on
rough
estimates
provided
by
the
American
Association
of
Textile
Chemists
and
Colorists
(
AATCC),
dyes
are
used
on
fabric
at
a
rate
of
about
4%
by
weight
(
AATCC,
2003).
A
medium­
sized
polo
cotton
shirt
of
regular
knit
construction
weighs
about
250
g.
Assuming
that
the
shirt
covers
0.659
m2
of
the
body's
surface
area
(
based
on
the
mean
adult
surface
area
for
the
torso,
including
the
neck
(
USEPA,
1997)),
the
cloth
weight
to
surface
area
ratio
is
379
g/
m2.
If
an
adult
wears
clothing
of
a
similar
weight
over
all
parts
of
the
body,
minus
the
head
(
1.69
m2
(
USEPA,
1997)),
then
the
weight
of
clothing
worn
by
an
adult
is
641
g.
Using
the
same
cloth
weight
to
surface
area
ratio,
the
weight
of
clothing
worn
by
a
toddler
is
214
g.
Area
mouthed,
for
lack
of
data,
is
assumed
to
be
equivalent
to
the
area
of
fingers
used
in
the
hand­
to­
mouth
exposure
estimates
(
i.
e.,
20
cm2
or
20
cm2
/
10,000
=
0.002
m2).
°
No
leaching
data
were
available
that
could
be
used
to
estimate
a
flux
rate
of
the
chemical
from
clothing.
It
has
been
conservatively
assumed
that,
over
the
course
of
a
day,
the
amount
of
chemical
transferred
is
the
full
quantity
of
chemical
present
in
the
clothing.
This
is
a
conservative
assumption
and
should
not
be
considered
as
representative
of
the
true
rate
at
which
the
chemical
would
be
transferred.
However,
as
a
screening­
level
assessment
the
risks
are
not
of
concern.

The
dermal
MOEs
calculated
for
both
toddler
and
adult
scenarios
are
not
of
concern
(
MOEs
=
119
and
185
for
toddlers
and
adults,
respectively).
The
short­
term
incidental
oral
MOE,
as
a
result
of
mouthing
treated
fabric,
is
not
of
concern
(
MOE
=
45,000).
The
short­
term
NOAELs
were
used
instead
of
the
intermediate­
term
NOAELs
because
all
of
the
residues
were
assumed
to
be
available
for
exposure
in
one
day
(
for
lack
of
any
residue
data).
See
ORE
Chapter
for
a
more
detailed
review.

4.4.2.3
Swimming
There
are
potential
postapplication
exposures
to
dihalodialkylhydantoin
associated
with
use
of
swimming
pools
and
spas.
Because
the
exposure
will
most
likely
be
much
greater
for
swimming
pools
than
for
spas,
based
on
the
amount
of
time
spent
in
the
water,
only
swimming
pool
scenarios
have
been
considered.

The
SWIMODEL
has
been
used
to
estimate
swimmer
exposure/
risk
to
dihalodialkylhydantoin
(
Dang,
1996).
Dermal,
inhalation,
and
ingestion
routes
were
considered
in
the
model.
Table
13
presents
the
dermal,
inhalation,
and
ingestion
MOEs
based
on
the
results
of
the
SWIMODEL.
MOEs
for
all
scenarios
are
much
greater
than
the
target
MOE
of
100.
The
swimming
scenario
is
unique
in
that
adults
(
not
just
children)
are
also
exposed
through
the
incidental
oral
route.
The
HIARC
selected
the
NOAEL
of
500
mg/
kg/
day
as
the
incidental
oral
endpoint
for
children
based
on
decreased
body
weight
gain
in
maternal
rabbits
seen
at
the
next
Page
36
of
57
highest
dose.
However,
for
the
swimming
scenario
it
is
important
to
highlight
the
fact
that
the
acute
dietary
NOAEL
is
100
mg/
kg/
day
based
on
skeletal
effects
in
offspring
at
the
next
highest
dose.
This
may
be
a
more
appropriate
endpoint
for
pregnant
swimmers.
As
indicated
in
Table
10,
the
MOEs
for
ingestion
would
be
sufficiently
protective
of
using
the
more
sensitive
endpoint
for
pregnant
swimmers.
See
ORE
Chapter
for
a
more
detailed
review.

Table
10.
Margins
of
Exposure
for
Swimming
Poola
Age
Type
of
Swimmer
Dermal
MOE
Inhalation
MOE
Ingestion
MOE
Adult
Competitive
2500000
52,100
47000
Adult
Non
competitive
7700000
501,000
280000
Child
7­
10
yr
Competitive
5800000
98,000
58000
Child
7­
10
yr
Non
competitive
3000000
93,300
29000
aMOE
=
NOAEL
(
mg/
kg/
day)/
Dose(
mg/
kg/
day).
Dermal
route
is
based
on
an
absorbed
dose,
and
therefore,
the
oral
endpoint
is
used
to
setimate
risk.
The
inhalation
and
ingestion
NOAELs
are
100
mg/
kg/
day
and
300
mg/
kg/
day
(
intermediate­
term),
respectively.
Target
MOE
=
100.

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
dihalodialkylhydantoin,
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),
shortterm
(
1­
30
days),
intermediate­
term
(
1­
6
months)
and
chronic
(
several
months
to
lifetime)
exposures.

5.1
Aggregate
Dietary
Risk
5.1.1
Acute
Aggregate
Risk
Assessment
The
acute
aggregate
assessment
includes
dietary
and
drinking
water
exposures
only.
The
acute
dietary
risk
estimates
from
indirect
food
uses
(
i.
e.,
use
in
food­
contact
packaging
and
treated
articles)
are
less
than
2%
of
the
aPAD
in
all
considered
scenarios.
Thus,
the
acute
dietary
(
food)
risk
estimate
associated
with
halohydantoins
is
below
the
Agency's
level
of
concern.
Drinking
water
exposure
is
not
expected,
but
could
occur
from
application
of
the
pesticide
to
industrial
water
systems.
Drinking
water
monitoring
data
are
not
available;
therefore,
AD
calculated
drinking
Page
37
of
57
water
level
of
comparisons
(
DWLOCs),
which
are
discussed
below
to
account
for
potential
drinking
water
exposures
from
the
exposure
from
once­
through
cooling
tower
uses.

The
short­
term
EEC
for
dihalodialkylhydantoin
in
surface
water
as
estimated
from
the
PDM4
Model
was
36
ppb,
or
36
ug/
L.
Details
of
this
analysis
can
be
found
in
the
Ecological
hazard
chapter
of
this
RED.
As
shown
in
Table
11,
the
acute
DWLOCs
are
greater
than
the
EEC,
indicating
that
acute
aggregate
food
and
drinking
water
exposure
do
not
exceed
the
Agency's
level
of
concern.

Table
11.
Acute
Aggregate
Exposure
and
Risk
Population
Subgroup
aPAD
mg/
kg/
day
Acute
Food
Exp1
mg/
kg/
day
Max
Acute
Water
Exp2
mg/
kg/
day
Surface
Water
EEC3
mg/
L
Acute
DWLOC4
mg/
L
Potential
Risk
Concern
Females
13­
50
years
1.0
4.6x10­
4
0.999
0.036
29986
No
Females
13­
50
years
(
alternate
FDA
method)
0.016
0.984
29520
No
1Acute
food
exposure
=
estimated
daily
intake
(
mg/
person/
day)
/
body
weight
(
70
kg)
2
Maximum
acute
water
exposure
(
mg/
kg/
day)
=
[(
aPAD
(
mg/
kg/
day)
­
acute
food
exposure
(
mg/
kg/
day)]
3
Based
on
PDM4
model.
4
Acute
DWLOC(

g/
L)
=
[
maximum
acute
water
exposure
(
mg/
kg/
day)
x
body
weight
(
kg)]
[
water
consumption
(
L)
x
10­
3
mg/

g]

Table
12
presents
the
total
chronic
dietary
exposure
estimate
for
dihalodialkylhydantoin,
and
the
chronic
DWLOCs.
The
chronic
PAD
and
the
chronic
dietary
(
food)
exposure
(
from
Table
7)
for
that
subgroup
were
used
to
calculate
the
chronic
DWLOC.
Two
methods
were
used
to
calculated
dietary
exposure,
and
calculations
are
presented
using
both
methods.

Based
on
the
use
of
the
PDM4
model
as
detailed
in
the
Ecological
hazard
chapter
of
this
RED,
the
chronic
maximum
EEC
for
dihalodialkylhydantoin
in
surface
water
was
calculated
as
313
ppb,
or
313
ug/
L.
As
shown
in
Table
12,
the
chronic
DWLOCs
are
greater
than
the
EEC,
indicating
that
aggregate
food
and
drinking
water
exposure
do
not
exceed
the
Agency's
level
of
concern.
Page
38
of
57
Table
12.
Chronic
Aggregate
Exposure
and
Risk
Population
Subgroup
cPAD
mg/
kg/
day
Chronic
Food
Exp1
mg/
kg/
day
Max
Chronic
Water
Exp2
mg/
kg/
day
Surface
Water
EEC3
mg/
L
Chronic
DWLOC4
mg/
L
Potential
Risk
Concern
General
Population
3.0
3.94x10­
4
2.999
0.3
104986
No
General
Population
(
alternate
FDA
method)
0.0137
2.986
104520
No
Females
13­
50
years
1.0
4.60x10­
4
0.999
29986
No
Females
13­
50
years
(
alternate
FDA
method)
0.016
0.984
29520
No
1Chronic
food
exposure
=
estimated
daily
intake
(
mg/
person/
day)
/
body
weight
(
70
kg
[
M];
60kg[
F])
2
Maximum
chronic
water
exposure
(
mg/
kg/
day)
=
[(
cPAD
(
mg/
kg/
day)
­
chronic
food
exposure
(
mg/
kg/
day)]
3
Based
on
PDM4
model.
4
Chronic
DWLOC(

g/
L)
=
[
maximum
chronic
water
exposure
(
mg/
kg/
day)
x
body
weight
(
kg)]
[
water
consumption
(
L)
x
10­
3
mg/

g]

5.2
Aggregate
Risk
5.2.1
Short­
and
Intermediate­
term
Aggregate
Risk
Dermal
and
Inhalation
aggregate
risks
were
considered
only
for
the
short­
term
in
the
aggregate
risk
evaluation.
This
is
because
homeowner
cleaning
scenarios
are
considered
shortterm
exposures
only
and
thus
do
not
involve
intermediate
or
long­
term
exposure.
Further,
not
all
of
the
non
­
dietary
scenarios
mentioned
in
this
risk
assessment
have
been
aggregated,
as
it
is
unlikely
that
all
of
the
scenarios
mentioned
in
the
exposure
assessment
have
a
reasonable
probability
of
occuring
together.
For
purposes
of
this
aggregate
assessment,
the
dietary
exposure
(
food
+
water)
is
aggregated
only
with
the
cleaning
scenarios
involving
wiping
of
hard
surfaces,
mopping,
and
cleaning
of
toilets
for
adults.
For
toddlers,
the
dietary
exposure
is
aggregated
with
the
single
dermal
scenario
of
floor
contact,
and
the
dietary
exposure
is
aggregated
separately
with
the
single
incidental
oral
floor
scenario.
This
is
because
the
study
and
endpoint
defining
the
toxicity
by
the
dermal
route
was
different
than
the
study
and
endpoint
defining
toxicity
by
the
dermal
route.
Clothing
is
not
included
in
the
aggregate
risk
because
a
screening
level
assessment
was
performed
in
which
it
was
assumed
that,
over
the
course
of
a
day,
the
amount
of
chemical
transferred
is
the
full
quantity
of
chemical
present
in
the
clothing.
As
noted
in
the
ORE
chapter,
this
is
a
conservative
assumption
and
should
not
be
considered
as
representative
of
the
true
rate
at
which
the
chemical
would
be
transferred.
Table
13
presents
a
summary
of
the
aggregate
dermal
and
inhalation
short­
term
risk
for
Page
39
of
57
adults.
As
shown,
the
aggregate
MOE
for
both
the
dermal
and
inhalation
exposure
was
not
of
concern.

Calculation
of
aggregate
MOEs
for
toddlers
from
dietary
exposure
and
either
dermal
or
inhalation
exposure
from
the
floor
treatment
also
showed
no
risk
of
concern.
Short­
term
aggregate
MOEs
were
calculated
as
1000
and
5000
for
the
dermal
and
inhalation
exposure
scenario,
while
intermediate­
term
aggregate
MOEs
were
calculated
as
909
and
3333
for
the
dermal
and
inhalation
exposure
scenario
respectively.
Page
40
of
57
Table
13
Short­
Term
Aggregate
Risk
and
DWLOC
Calculations
for
Adults
(
1/
MOE
Approach
­
All
Target
MOEs
Identical)

Population
Short­
Term
Scenario
Target
Aggregate
MOE
MO
E
food1
MOE
dermal2
MOE
inhalation
3
Short­
Term
Aggregate
MOE
(
food
and
dermal
residential)
4
Short­
term
Aggregate
MOE
(
food
+

inhalation
residential)
5
MOE
water6
Allowable
water
exposure7
(
mg/
kg/
day)
Surface
Water
EEC8
(

g/
L)
DWLOC9
(

g/
L)

Adult
100
3649
6
7090
196000
5988
31250
101
4.9
4
147000
1
MOE
food
=
[(
short­
term
oral
NOAEL)/(
chronic
dietary
exposure)]
Oral
NOAEL
of
500
mg/
kg/
day
with
chronic
exposure
of
0.0137.

2MOE
dermal
=
[(
short
­
term
dermal
NOAEL)/
dermal
residential
exposure)]
dermal
NOAEL
of
390
mg/
kg/
day
used
with
total
exposure
of
0.055
mg/
kg/
day
from
cleaning
scenarios.

3
MOE
inhalation
=
[(
inhalation
NOAEL)/(
high­
end
inhalation
residential
exposure)]
Inhalation
NOAEL
of
100
mg/
kg/
day
used
with
total
exposure
of
0.00051
mg/
kg/
day
4
Aggregate
MOE
(
food
and
dermal
residential)
=
1
÷
[
[(
1
÷
MOE
food)
+
(
1
÷
MOE
dermal)]]

5
Aggregate
MOE
(
food
and
inhalation
residential)
=
1
÷
[
[(
1
÷
MOE
food)
+
(
1
÷
MOE
inhalation)]]

6
Water
MOE
=
1
÷
[[(
1
÷
Target
Aggregate
MOE)
­
(
1
÷
Aggregate
MOE
(
food
and
residential)]]

7
Allowable
water
exposure
=
Short
or
Intermediate
Term
Oral
NOAEL
÷
MOE
water
8using
PDM4
model
9
DWLOC(

g/
L)
=
[
allowable
water
exposure
(
4.9mg/
kg/
day)
x
body
weight
(
60kg)]

[
water
consumption
(
2L)
x
10­
3
mg/

g]
Page
41
of
57
6.0
OCCUPATIONAL
EXPOSURE
EPA
has
assessed
the
exposures
and
risks
to
occupational
workers
that
handle
and
apply
dihalodialkylhydantoin
in
memorandum
attached
as
ORE
Chapter.
This
section
summarizes
the
results
of
the
occupational
exposure/
risk
assessment.

6.1
Industrial
Processes
(
Handlers)

Dihalodialkylhydantoin
products
are
used
in
a
variety
of
industrial
applications,
all
of
which
relate
to
preventing
slime
formation
in
water
systems.
Concentrations
of
dihalodialkylhydantoin
in
these
products
range
from
90%
to
98%,
are
generally
formulated
as
tablets,
pellets,
briquettes,
or
granules.
The
remaining
formulations
are
either
gels,
wettable
powders,
or
ready­
to­
use
solutions,
and
all
may
be
considered
as
solid
(
as
opposed
to
liquid)
formulations.

The
handlers
were
identified
as
those
individuals
who
use
dihalodialkylhydantoin
in
industrial/
commercial
water
systems
to
limit
microbial
growth.
Systems
in
which
dihalodialkylhydantoin
is
used
include
recirculating
cooling
water,
once­
through
cooling
water,
pulp
and
paper
process
water,
photo
processing
water,
and
transportation
cleaning
systems.
The
application
rates
were
assumed
to
be
the
maximum
rates
listed
on
the
product
labels.
The
amount
of
pesticide
handled
were
based
on
a
report
containing
use
information
for
selected
scenarios
related
to
antimicrobials
(
Dang,
1996).
The
risks
were
assessed
to
the
handlers
using
the
dermal
and
inhalation
exposure
data
for
loading
powder
formulations
from
the
proprietary
Chemical
Manufacturers
Association
(
CMA)
antimicrobial
exposure
study
(
USEPA,
1999).

The
following
two
primary
handler
exposure
scenarios
have
been
identified:

°
Placing
the
dihalodialkylhydantoin
tablets/
pellets
into
cooling
and
process
water
systems,
and
°
Pouring
dihalodialkylhydantoin
granules/
powders
into
a
feeder
for
cooling
and
process
water
systems.

These
two
types
of
exposure
scenarios
were
assessed
for
each
of
the
water
systems
in
question.
The
methods
for
applying
gels,
briquettes,
and
ready­
to­
use
solutions
are
nearly
identical
to
at
least
one
of
the
two
methods
described
above,
based
on
the
directions
on
the
label.
Therefore,
although
the
two
exposure
scenarios
considered
include
only
products
that
are
tablets,
pellets,
granules,
or
wettable
powders,
these
scenarios
should
be
sufficient
to
describe
the
risks
associated
with
all
formulations.

The
results
of
the
MOE
analysis
are
presented
in
Table
14.
For
industrial
use,
the
shortand
intermediate­
term
dermal
and
inhalation
MOEs
for
the
primary
handlers
wearing
long
pants,
long
sleeved
shirts,
chemical
resistant
gloves,
goggles,
and
a
face
shield
(
as
required
by
the
label)
were
determined.
Dermal
MOEs
range
from
a
high
of
151,000
for
solid
pour
in
photo
processing
water
systems,
to
76
for
solid
place
in
once­
through
cooling
water
systems.
Except
for
oncethrough
cooling
water
systems,
all
MOEs
are
above
the
EPA
required
margin
of
exposure
(
100).
Page
42
of
57
Table
14.
Short­
and
Intermediate­
term
Risks
Associated
with
Industrial
Uses
of
Dihalodialkylhydantoin
Exposure
Scenario
Method
of
Application
Dermal
Dose
(
mg/
kg/
day)
a
Dermal
MOE
b
Inhalation
Dose
(
mg/
kg/
day)
a
Inhalation
MOE
b
Recirculating
Cooling
Water
Solid
Place
1.0
390
0.0216
4630
Solid
Pour
0.0391
9960
0.00127
78800
Once­
Through
Cooling
Water
Solid
Place
5.1
76
0.11
909
Solid
Pour
0.20
1950
0.0065
15385
Wastewater
Treatment
Solid
Place
2.5
156
0.054
1850
Solid
Pour
0.0979
3990
0.00317
31500
Pulp
and
Paper
Process
Water
Solid
Place
0.333
2730
0.00720
32,400
Solid
Pour
0.0130
69,700
0.000423
552,000
Photo
Processing
Water
Solid
Place
0.0661
5900
0.00143
70100
Solid
Pour
0.00259
151000
0.0000838
1190000
Air
Washer
Solid
Place
2.5
156
0.054
1850
Solid
Pour
0.0979
3990
0.00317
31500
Evaporative
Cooler
Solid
Place
2.45
159
0.0529
1890
Solid
Pour
0.0959
4070
0.00311
32200
Cannery
Water
Solid
Place
2.45
159
0.0529
1890
Solid
Pour
0.0959
4070
0.00311
32200
a
Dose
(
mg/
kg/
day)
=
[
unit
exposure
(
mg/
lb
ai)
*
Appl.
rate
(
lb
ai/
gallon)
*
gallons
handled
/
Body
weight
(
70
kg).
See
Occupational
and
Residential
Exposure
chapter
for
specific
details.
b
MOE
=
NOAEL
(
mg/
kg/
day)
/
Daily
Dose
[
Where
short­
and
intermediate­
term
dermal
and
inhalation
NOAEL
=
390
mg/
kg/
day
and
100
mg/
kg/
day,
respectively].
Target
MOE
is
100.

6.2
Material
Preservatives
and
Commercial/
Institutional/
Industrial
Premises
and
Equipment
and
Swimming
Pools
(
Handlers)

Commercial
use
of
dihalodialkylhydantoin
is
similar
in
purpose
to
industrial
use
 
it
is
used
to
prevent
slime
formation
in
water
systems.
In
addition,
it
is
used
as
a
material
preservative
in
paints,
etc.
Six
scenarios
have
been
identified
to
represent
the
high
end
exposure
potential
for
these
uses:

°
Liquid
pour
of
product
into
paint
during
manufacturing
as
a
material
preservative,
°
Solid
place
of
product
in
air
conditioner
/
humidifier
drip
pans,
°
Solid
place
of
product
in
ornamental
fountains,
°
Solid
place
of
product
for
use
in
transportation
cleaning
water
systems,
°
Commercial
painters
(
brush/
airless
sprayer);
°
Solid
place/
pour
of
product
in
commercial
swimming
pools
and
spas.

The
material
preservative
use
assessed
for
paints
is
believed
to
be
representative
of
the
other
preservative
uses
on
the
labels
such
as
detergents,
fabric
softeners,
household
cleaning
Page
43
of
57
products,
surfactants,
polymer
emulsions,
coatings,
textiles,
adhesives,
sealants
and
caulks,
and
inks.
Therefore,
a
separate
commercial
use
of
household
cleaning
products
has
not
be
assessed.

Very
little
data
are
available
at
this
time
regarding
typical
amounts
of
product
handled
by
workers.
For
a
worker
performing
air
conditioning
maintenance
in
a
large
institution,
it
has
been
assumed
that
3
air­
conditioner
units
were
maintained
at
a
time.
A
large
ornamental
fountain
was
assumed
to
be
the
same
size
as
an
average
residential
swimming
pool.
Assumptions
for
the
in­
bay
car
wash
are
based
on
information
from
the
International
Carwash
Association
and
from
anecdotal
evidence.
The
EPA
calculated
the
exposures
for
workers
at
a
commercial/
public
swimming
pool,
using
the
assumption
that
a
large
commercial/
public
swimming
pool
size
is
200,000
gallons,
and
that
a
large
commercial
spa's
volume
is
~
1000
gallons.

The
results
of
the
MOE
analysis
for
both
baseline
(
ungloved)
and
PPE
(
gloved)
scenarios
are
presented
in
Table
15
and
16,
respectively.
For
commercial
uses,
the
short­
and
intermediate
term
dermal
MOEs
for
the
handlers
wearing
PPE
range
from
140
to
151,000.
An
MOE
lower
than
the
target
MOE
was
found
for
only
one
scenario
 
placing
tablets
into
public
swimming
pools
wearing
baseline
protection
(
MOE=
46).
However,
the
product
labels
state
that
gloves
should
be
worn
when
placing
tablets
into
swimming
pools.
When
gloves
are
used
(
see
Table
16)
the
risks
are
mitigated
for
the
placing
of
tablets
(
MOE
=
7,500).

Metal
Working
Fluids:

The
potential
inhalation
and
dermal
exposure
may
exist
when
using
treated
metal
working
fluid.
A
screening­
level
long­
term
inhalation
exposure
estimate
for
treated
metal
working
fluids
has
been
developed
using
the
OSHA
PEL
for
oil
mist.
The
Agency
conducted
the
screening
level
assessment
for
metal
working
fluids
using
the
Chemical
Engineering
Branch
(
CEB)
model
(
U.
S.
EPA,
1991).
Exposure
assumptions
used
in
the
model
are
presented
in
Dang,
1997.
The
CEB
model
uses
measured
and/
or
assumed
airborne
oil
mist
concentrations
for
metal
working
operations.
Since
no
measured
concentrations
are
available
for
hydantooins,
the
high­
end
oil
mist
concentration
is
based
on
the
OSHA's
Permissible
Exposure
Limit
(
PEL)
of
5
mg/
m3
(
NIOSH,
1998).
The
label
indicates
that
0.45%
(
i.
e.,
0.0045)
of
the
product
is
added
to
metal
working
fluids
and
of
that,
only
52.4%
is
the
active
ingredient.
Therefore,
the
upper
bound
air
concentration
of
hydantoin
that
a
worker
is
exposed
to
is
5
mg/
m3
x
0.0045
x
0.524
or
an
air
concentration
of
0.012
mg/
m3.
Additionally,
the
following
assumption
were
made
in
the
assessment:
the
inhalation
rate
for
adults
is
1.25
m3
/
hr;
the
exposure
duration
is
8
hours;
and
body
weight
is
70
kg.
Using
these
assumptions,
the
long­
term
dose
was
calculated
to
be
0.0017
mg/
kg/
day,
resulting
in
a
long­
term
MOE
of
59,000.
Therefore,
the
calculated
MOE
indicates
that
the
inhalation
risks
do
not
exceed
the
Agency's
level
of
concern
for
machinist
exposures
to
metal
working
fluid.

A
screening­
level
long­
term
dermal
exposure
estimate
was
derived
from
the
2­
Hand
Dermal
Immersion
in
Liquid
Model
in
ChemSTEER
(
EPA/
OPPT).
The
model
is
available
at
www.
epa.
gov/
opptintr/
exposure/
docs/
chemsteer.
htm
.
The
weight
fraction
of
hydantoin
in
metal
working
fluids
is
0.0024
(
0.0045
formulated
product
added
to
oil
x
0.524
ai
in
formulated
product
=
0.0024).
Based
on
the
model
for
emersion
of
hands
in
metal
working
fluids,
the
long­
term
Page
44
of
57
dermal
dose
is
estimated
at
0.3
mg/
kg/
day.
The
long­
term
dermal
MOE
is
1,300
(
i.
e.,
dermal
NOAEL
of
390
mg/
kg/
day
/
potential
dose
of
0.3
mg/
kg/
day).
The
dermal
MOE
is
above
the
target
MOE
of
100,
and
therefore,
the
risk
is
not
of
concern.

Table
15.
Short­
and
Intermediate­
term
Risks
Associated
with
Material
Preservatives
and
Commercial,
Institutional,
and
Swimming
Pool
Uses
of
Dihalodialkylhydantoin
(
Baseline
Clothing
Scenario)
a
Exposure
Scenario
Method
of
Application
Dermal
Dose
(
mg/
kg/
day)
a
Dermal
MOE
b
Inhalation
Dose
(
mg/
kg/
day)
a
Inhalation
MOE
b
Material
Preservatives
and
Commercial/
Institutional
Premises
Material
Preservative
Pour
Liquid
0.2
1900
0.0054
19000
Air
Conditioner
/
Humidifier
Drip
Pans
Solid
Place
0.454
860
0.000058
1,730,000
Ornamental
Fountains
Solid
Place
0.771
506
0.0000985
1,010,000
Transportation
Cleaning
Solid
Place
0.148
2630
0.0000189
5,280,000
Swimming
Pools
/
Spas
Swimming
Pools
(
Residential
 
backyard)
Solid
Place
0.12
3200
0.000015
6500000
Solid
Pour
0.85
460
0.00046
220000
Swimming
Pools
(
Commercial/
Public)
Solid
Place
1.2
325
0.000153
653000
Solid
Pour
8.46
46
0.00457
21900
Spas
Solid
Place
0.396
984
0.0000506
1,970,000
Solid
Pour
2.8
139
0.00151
66,500
a
Dose
(
mg/
kg/
day)
=
[
unit
exposure
(
mg/
lb
ai)
*
Appl.
rate
(
lb
ai/
gallon)
*
gallons
handled
/
Body
weight
(
70
kg).
See
Occupational
and
Residential
Exposure
chapter
for
specific
details.
b
MOE
=
NOAEL
(
mg/
kg/
day)
/
Daily
Dose
[
Where
short­
and
intermediate­
term
dermal
and
inhalation
NOAEL
=
390
mg/
kg/
day
and
100
mg/
kg/
day,
respectively].
Target
MOE
is
100.
Page
45
of
57
Table
16.
Short­
and
Intermediate­
term
Risks
Associated
with
Commercial,
Institutional,
and
Swimming
Pool
Uses
of
Dihalodialkylhydantoin
(
with
gloves
only)
a
Exposure
Scenario
Method
of
Application
Dermal
Dose
(
mg/
kg/
day)
a
Dermal
MOE
b
Inhalation
Dose
(
mg/
kg/
day)
a
Inhalation
MOE
b
Commercial/
Institutional
Premises
Air
Conditioner
/
Humidifier
Drip
Pans
Solid
Place
0.017
22,940
0.000058
1,730,000
Ornamental
Fountains
Solid
Place
0.029
13,450
0.0000985
1,010,000
Transportation
Cleaning
Solid
Place
0.0057
68,420
0.0000189
5,280,000
Swimming
Pools
/
Spas
Swimming
Pools
(
Commercial/
Public)
Solid
Place
0.046
8480
0.000153
653000
Solid
Pour
0.0517
7538
0.00457
21900
Spas
Solid
Place
0.0072
5,420
0.0000506
1,970,000
Solid
Pour
0.00814
47,900
0.00151
66,500
a
Dose
(
mg/
kg/
day)
=
[
unit
exposure
(
mg/
lb
ai)
*
Appl.
rate
(
lb
ai/
gallon)
*
gallons
handled
/
Body
weight
(
70
kg).
See
Occupational
and
Residential
Exposure
chapter
for
specific
details.
b
MOE
=
NOAEL
(
mg/
kg/
day)
/
Daily
Dose
[
Where
short­
and
intermediate­
term
dermal
and
inhalation
NOAEL
=
390
mg/
kg/
day
and
100
mg/
kg/
day,
respectively].
Target
MOE
is
100.

6.3
Agricultural
Premises
and
Aquatic
Area
Uses
(
Handlers)

One
agricultural
premise
use
and
one
aquatic
area
use
have
been
identified.

°
Solid
pour/
place
of
product
into
chemigation
systems,
°
Solid
pour
of
product
into
vehicle
and
foot
baths
at
greenhouse
entrances.

Use
of
dihalodialkylhydantoin
in
chemigation
systems
is
via
loading
of
a
brominator
feed
system,
through
which
the
product
is
dispensed
via
dissolution
as
feed
water
is
passed
through
the
tank.
The
amount
of
dihalodialkylhydantoin
that
will
be
used
in
the
irrigation
systems
will
depend
greatly
on
the
size
of
the
greenhouse/
nursery
and
the
amount
of
irrigation
necessary
for
the
particular
crop/
climatic
conditions.
The
amount
of
footbaths
that
should
be
used
for
the
assessment
is
also
in
question.
From
anecdotal
evidence,
1
gal
of
water
is
used
for
each
footbath,
and
1"
of
water
use
for
irrigation
can
be
assumed.
It
has
also
been
assumed
that,
for
chemigation,
the
product
will
be
used
on
10
acres
of
crop.
From
these
assumptions,
the
total
amount
of
water
applied
for
chemigation
is
270,000
gallons.
This
scenario
is
not
representative
of
the
available
exposure
data
and
the
uncertainty
level
is
deemed
high.
The
exposures
maybe
overestimated
because
of
the
extrapolation
to
such
a
high
amount
of
water
applied.
The
estimated
MOEs
are
presented
in
Table
17.
All
MOEs
calculated
are
of
concern
(
i.
e.,
MOEs
less
than
the
target
MOE
of
100).
No
postapplication
exposures
were
considered.
Page
46
of
57
Table
17.
Short­
and
Intermediate­
term
Risks
Associated
with
Agricultural
Premises
and
Aquatic
Areas
Uses
Exposure
Scenario
Method
of
Application
Absorbed
Dermal
Dose
(
mg/
kg/
day)
a
Dermal
MOE
b
Inhalation
Dose
(
mg/
kg/
day)
a
Inhalation
MOE
b
Aquatic
Areas
Greenhouse
and
Nursery
Irrigation
Systems
Solid
Place
27.5
14.2
0.595
168
Solid
Pour
1.08
362
0.0289
3460
Solid
Place
NA
NA
0.595
168
Solid
Pour
176
2.21
0.0953
1050
Agricultural
Premises
Greenhouse
Foot
Bath
Solid
Pour
0.00002
19,500,000
0.000000536
187000000
0.00327
119000
0.00000177
56600000
a
Dose
(
mg/
kg/
day)
=
[
unit
exposure
(
mg/
lb
ai)
*
Appl.
rate
(
lb
ai/
gallon)
*
gallons
handled
/
Body
weight
(
70
kg).
See
Occupational
and
Residential
Exposure
chapter
for
specific
details.
b
MOE
=
NOAEL
(
mg/
kg/
day)
/
Daily
Dose
[
Where
short­
and
intermediate­
term
dermal
and
inhalation
NOAEL
=
390
mg/
kg/
day
and
100
mg/
kg/
day,
respectively].
Target
MOE
is
100.

6.4
Postapplication
Exposure
(
All
Occupational
Uses)

Postapplication
inhalation
exposures
may
occur
in
the
industrial
settings
around
the
water
systems
via
inhalation,
and
dermal
exposures
may
occur
while
maintaining
industrial
equipment.
However,
occupational
postapplication
dermal
and
inhalation
exposures
to
dihalodialkylhydantoin
are
likely
to
be
minimal
compared
to
handler
exposure
because
of
dilution
during
processing.
No
postapplication
exposure
data
have
been
submitted
to
the
agency
to
determine
the
extent
of
postapplication
exposures
in
the
industrial
settings.
Inhalation
exposures
are
expected
to
be
minimal
because
aerosol
generation
is
not
expected
and
the
vapor
pressure
of
dihalodialkylhydantoin
is
low.

7.0
ENVIRONMENTAL
FATE
ASSESSMENT
7.1
Environmental
Fate
Assessment
The
Agency
does
not
have
a
complete
database
for
environmental
fate
studies
on
dihalodialkylhydantoin.
However,
hydrolysis
appears
to
be
the
major
route
for
dissipation.
Dihalodialkylhydantoin
has
been
shown
to
hydrolyze
relatively
rapidly.
It
also
degrades
rapidly
in
an
anaerobic
aquatic
environment
with
an
observed
half­
life
of
less
than
4
hours;
there
are
indications
that
this
short
half­
life
appeared
to
be
independent
of
aerobic
or
anaerobic
conditions.
The
rapid
hydrolysis,
under
abiotic
conditions,
show
half­
lives
of
less
than
30
days
in
pH
5,
pH
7,
and
pH
9
(
in
buffered
solutions),
which
indicated
that
hydrolysis
is
an
early
step
in
the
degradation
process.
However,
the
major
degradate,
dimethylhydantoin
(
DMH),
was
hydrolytically
stable
at
pH
5,
pH
7,
and
pH
9
and
may
possibly
leach
in
the
soil
profile
or
move
with
surface
water
runoff
Page
47
of
57
and
may
pose
environmental
concerns.
An
aqueous
photolytic
study
on
dimethylhydantoin,
conducted
at
pH
7
and
at
25
±
1

C
in
the
presence
of
xenon
arc
as
light
source,
yielded
a
first
order
rate
constant
of
7.89x10­
4/
day
which
translates
into
a
half
life
of
878
days.
Aqueous
photolytic
stability
means
that
surface
water
runoff
of
DMH
can
be
a
source
of
concern
for
drinking
water
contamination.
The
Agency
lacks
any
data
on
halohydantoins
as
far
as
mobility
(
soil
column
leaching)
is
concerned,
as
well
as
binding
constants
to
soils
to
indicate
if
dihalodialklhydantoins
will
be
persistent
in
soils.
Because
of
lack
of
data,
the
Agency
cannot
assess
if
halohydantoins
are
bioaccumulative
and
if
these
can
be
a
source
of
concern
for
the
aquatic
organisms.

7.2
Environmental
Fate
and
Transport
Dihalodialkylhydantoin
degrades
relatively
rapidly
in
water
under
abiotic
conditions.
However,
there
is
environmental
concern
for
soil
or
surface
water
contamination
from
the
major
degradate
DMH,
as
DMH
is
hydrolytically
and
photolytically
stable.
No
additional
fate
data
on
dimethylhydantoins
are
available
to
further
assess
fate
of
this
chemical.

8.0
ECOTOXICOLOGY
and
ENVIRONMENTAL
RISK
ASSESSMENT
8.1
Ecotoxicity
Data:

Halogenated
hydantoins
show
varying
toxicity,
depending
on
the
number
of
halogens
(
bromine
or
chlorine)
on
the
molecule.
The
halogens
dissociate
from
the
DMH
core
upon
exposure
to
water;
therefore,
DMH
was
considered
to
be
the
moiety
of
concern
for
environmental
exposure
and
ecological
toxicity.
A
summary
of
ecotoxicological
endpoints
for
DMH
is
provided
in
the
table,
below:
Page
48
of
57
Table
18:
Summary
of
Ecotoxicity
Endpoints
Test
type
Species
%
a.
i.
Endpoint
EPA
MRID
#
Toxicity
Category
Avian
acute
oral
(
71­
1/
850.2100)
Northern
bobwhite
(
Colinus
virginianus
96
LD50
=
1839mg/
kg
NOEL
=
1350
mg/
kg
147319
Slightly
toxic
Avian
dietary
(
71­
2/
850.2200)
Northern
bobwhite
(
Colinus
virginianus)
96
LC50
>
5620
ppm
147321
Practically
nontoxic
Avian
dietary
(
71­
2/
850.2200)
Mallard
(
Anas
platyrhynchos)
97.2
>
5000
ppm
NOEC
=
5000
ppm
432899­
03
Practically
nontoxic
Freshwater
fish
acute
(
72­
1/
850.1075)
Rainbow
trout
(
Oncorhynchus
mykiss)
97.1
LC50
>
972
mg/
L
NOEC
=
972
mg/
L
423736­
01
Practically
nontoxic
Freshwater
fish
acute
(
72­
1/
850.1075)
Bluegill
(
Lepomis
macrochirus)
97.1
LC50
>
1,017
mg/
L
NOEC
=
1,017
mg/
L
423685­
01
Practically
nontoxic
Fish
early
lifestage
(
72­
4/
850.1300)
Fathead
minnow
(
Pimephales
promelas)
99.9
NOEC
=
14
mg/
L(
dry
weight)
LOEC
=
29
mg/
L
427217­
02
(
chronic
endpoints
are
not
assigned
a
toxicity
category)

Freshwater
invertebrate
acute
(
72­
2/
850.1010)
Daphnia
magna
97.1
EC50
>
1070
mg/
L
NOEC
=
1070
mg/
L
423736­
03
Practically
nontoxic
Marine/
estuari
ne
fish
acute
(
72­
3a/
850.1075)
Sheepshead
minnow
(
Cyprinodon
variegatus)
97.1
LC50
>
1006
mg/
L
NOEC
=
1006
mg/
L
423747­
01
Practically
nontoxic
Marine/
estuari
ne
invertebrate
acute
(
72­
3c/
850.1045)
Mysid
(
Mysidopsis
bahia)
97.1
LC50
>
921mg/
L
(
limit
test)
423736­
02
Practically
nontoxic
Marine/
estuari
ne
bivalve
acute
(
72­
3b/
850.1025)
Eastern
oyster
(
Crassostrea
virginica)
shell
deposition
97.2
EC50
>
125
mg/
L
NOEC
=
125
mg/
L
432899­
02
Practically
nontoxic
As
indicated
in
the
above
table,
DMH
demonstrates
low
toxicity
to
terrestrial
and
aquatic
animals.
Page
49
of
57
8.2
Environmental
Exposure
Modeling
The
PDM4
Model
was
used
to
estimate
exposure
from
once­
through
cooling
tower
uses.
The
details
of
this
model
are
found
in
the
Environmental
Modeling
Chapter
of
this
document.
A
low­
flow
power
plant
(
100
+
10
million
gallons
per
day)
was
used
as
the
scenario
providing
the
maximum
concentrations
of
DMH
in
the
receiving
water,
e.
g.,
the
"
worst
case"
scenario.
Actual
concentrations
in
receiving
waters
are
likely
lower,
and
will
likely
not
show
the
increasing
trend
indicated
in
Table
19,
due
to
higher
flow
rates
and
possible
degradation/
dissipation
of
DMH
by
mechanisms
other
than
hydrolysis.
A
summary
of
the
estimated
environmental
concentrations
(
EECs)
over
time
is
provided
below:

Table
19:
Summary
of
Estimated
Environmental
Concentrations
of
DMH
in
Rivers
Receiving
Outfall
from
Low­
Flow
Power
Plants
Using
Once­
Through
Cooling
Systems
Time
Period
Modeled
Peak
Concentration
of
DMH
Duration
of
Peak
Concentration
4
days
36.0
ppb
24
hours
30
days
210
ppb
24
hours
60
days
313
ppb
24
hours
The
model
was
also
used
to
determine
the
percent
of
days
per
year
various
"
concentrations
of
concern"
were
exceeded
for
several
power
plant
scenarios.
Details
of
these
results
are
provided
in
the
Environmental
Modeling
Chapter.

8.3
Environmental
Risk
Assessment
a.
Terrestrial
Organisms:

No
model
is
available
to
estimate
exposure
and
risk
to
birds
and
mammals
from
discharge
of
once­
through
cooling
system
effluents
into
surface
waters.
The
low
EECs,
coupled
with
the
generally
low
toxicity
of
DMH
to
birds
and
mammals,
make
risk
to
these
organisms
unlikely.
There
are
no
data
available
to
assess
the
phytotoxicity
of
DMH
at
this
time;
therefore,
the
risk
to
terrestrial/
semi­
aquatic
plants
cannot
currently
be
assessed.

b.
Aquatic
Organisms:

Using
the
worst­
case
scenario
of
a
low­
flow
power
plant
using
hydantoins
for
oncethrough
cooling
system
treatment,
the
following
risk
quotients
(
RQ)
were
calculated
for
aquatic
organisms:
Page
50
of
57
Table
20:
Aquatic
Organism
Risk
Quotients
for
DMH
Used
in
Once­
Through
Cooling
of
Low­
Flow
Power
Plants
Endpoint
Type
Species
Value
EEC
(
from
Table
7)
RQ
(
EEC/
LC50)

Freshwater
Fish
Acute
Rainbow
trout
(
Oncorhynchus
mykiss)
LC50
>
972
mg/
L
(
MRID
­
423736­
01)
36.0
ppb
(
0.036
mg/
L)
0.000037
Freshwater
Invertebrate
Acute
Daphnia
magna
EC50
>
1070
mg/
L
NOEC
=
1070
mg/
L
(
MRID
423736­
03)
36.0
ppb
(
0.036
mg/
L)
0.000034
Freshwater
Fish
Chronic
Fathead
minnow
(
Pimephales
promelas)
NOEC
=
14
mg/
L
LOEC
=
29
mg/
L
(
MRID
­
427217­
02)
313
ppb
(
0.313
mg/
L)
0.022
Using
the
very
conservative
EECs
provided
by
modeling
the
low­
flow
power
plant,
no
LOCs
are
exceeded.
Expressed
as
number
of
days
exceedance,
using
the
most
sensitive
parameter
of
14.0
mg/
L
(
14000
ppb)
(
freshwater
fish
chronic
NOEC)
as
the
"
concentration
of
concern"
and
the
exceedance
curve
generated
in
the
Environmental
Modeling
chapter,
the
chance
of
this
concentration
being
exceeded
by
any
of
the
power
plant
scenarios
is
extremely
low,
less
than
once
every
two
years.
Other
uses
of
hydantoin
products
are
indoor
or
contained
(
e.
g.,
swimming
pool)
uses,
and
should
not
result
in
appreciable
environmental
exposure
when
products
are
used
as
labeled.
Risk
to
freshwater
fish
and
aquatic
invertebrates
is
not
anticipated
from
the
use
of
hydantoins
in
once­
through
cooling
systems.
Marine/
estuarine
fish
are
generally
less
sensitive
than
freshwater
fish
to
hydantoins,
and
marine/
estuarine
invertebrates
are
comparably
as
sensitive
to
DMH
as
freshwater
invertebrates,
so
the
freshwater
RQ
are
presumed
to
be
protective
of
marine/
estuarine
species.
Risk
to
aquatic
plants
cannot
be
assessed
due
to
the
lack
of
phytotoxicity
data.

8.4
Endangered
Species
Considerations
The
Agency
has
developed
the
Endangered
Species
Protection
Program
to
identify
pesticides
whose
use
may
cause
adverse
impacts
on
endangered
and
threatened
species,
and
to
implement
mitigation
measures
that
address
these
impacts.
The
Endangered
Species
Act
requires
federal
agencies
to
ensure
that
their
actions
are
not
likely
to
jeopardize
listed
species
or
adversely
modify
designated
critical
habitat.
To
analyze
the
potential
of
registered
pesticide
uses
to
affect
any
particular
species,
EPA
puts
basic
toxicity
and
exposure
data
developed
for
risk
assessments
into
context
for
individual
listed
species
and
their
locations
by
evaluating
important
ecological
parameters,
pesticide
use
information,
the
geographic
relationship
between
specific
pesticide
uses
and
species
locations,
and
biological
requirements
and
behavioral
aspects
of
the
particular
species.
Page
51
of
57
A
determination
that
there
is
a
likelihood
of
potential
impact
to
a
listed
species
may
result
in
limitations
on
use
of
the
pesticide,
other
measures
to
mitigate
any
potential
impact,
or
consultations
with
the
Fish
and
Wildlife
Service
and/
or
the
National
Marine
Fisheries
Service
as
necessary.

Risk
to
Endangered
birds
and
mammals
is
not
anticipated
from
the
use
of
hydantoin
products
due
to
low
exposure
and
low
toxicity.
Calculated
RQs
for
fish
and
aquatic
invertebrates
from
the
once­
through
cooling
use
are
well
below
LOCs
for
Endangered
species;
other
uses
of
hydantoin
products
are
indoor
or
contained
(
e.
g.,
swimming
pool)
uses,
and
should
not
result
in
appreciable
environmental
exposure
when
products
are
used
as
labeled.
Therefore,
risk
to
Endangered
fish
and
aquatic
invertebrate
species
is
not
anticipated
from
the
use
of
hydantoin
products.
Risk
to
Endangered
plants
cannot
be
addressed
due
to
the
lack
of
phytotoxicity
data.

9.0
INCIDENT
REPORT
ASSESSMENT
Dihalodialkylhydantoin
is
an
active
ingredient
used
in
a
variety
of
products
(
e.
g.
for
treatment
of
swimming
pools,
spas
and
hot
tubs,
and
toilet
bowl
water.
The
purpose
of
this
chapter
is
to
review
the
evidence
of
health
effects
in
humans
resulting
from
exposure
to
dihalodialklhydantoins.
In
particular,
the
acute
and
chronic
toxicity,
teratogenic/
reproductive
effects,
and
carcinogenicity
are
discussed.

Two
approaches
are
used
in
this
section:

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

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

There
are
many
incidences
that
have
been
reported
associated
with
exposure
to
end­
use
products
containing
dihalodialklhydantoins.
Dermal,
ocular,
and
inhalation
are
the
primary
routes
of
exposure.
Most
of
the
incidences
are
related
to
irritation
and/
or
allergic
type
reaction.
The
most
common
symptoms
reported
for
cases
of
dermal
exposure
were
skin
irritation/
burning,
rash,
itching,
skin
discoloration/
redness,
blistering,
allergic
type
reactions
including
hives/
welts,
allergic
contact
dermatitis,
and
bleeding
also
have
been
reported.
The
most
common
symptoms
reported
for
cases
of
ocular
exposure
were
eye
irritation/
burning.
Eye
pain
and
swelling
of
eyes
also
has
been
reported
in
some
incidences.

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,
headache.
Seizure
and
heart
palpitation
also
have
been
reported.

Although
oral
exposure
is
considered
a
minor
route
of
exposure
for
Dihalodialkylhydantoin
use,
irritation
to
mouth/
throat/
nose,
vomiting/
nausea/
abdominal
pain
have
been
reported
in
the
cases
of
ingestion.
Page
52
of
57
9.1
Incident
Report
Data
Associated
with
Health
Effects
of
Dihalodialkylhydantoin
Exposure
The
following
databases
have
been
consulted
for
the
poisoning
incident
data
on
the
active
ingredient
dihalodialklhydantoins:

°
OPP
Incident
Data
System
(
IDS)
­
The
Incident
Data
System
of
The
Office
of
Pesticide
Programs
(
OPP)
of
the
Environmental
Protection
Agency
(
EPA)
contains
reports
of
incidents
from
various
sources,
including
registrants,
other
federal
and
state
health
and
environmental
agencies
and
individual
consumers,
submitted
to
OPP
since
1992.
Reports
submitted
to
the
Incident
Data
System
represent
anecdotal
reports
or
allegations
only,
unless
otherwise
stated.
Typically,
no
conclusions
can
be
drawn
implicating
the
pesticide
as
a
cause
of
any
of
the
reported
health
effects.
Nevertheless,
sometimes
with
enough
cases
and/
or
enough
documentation,
risk
mitigation
measures
may
be
suggested.
A
total
of
126
individual
incident
cases
submitted
to
the
EPA
Office
of
Pesticide
Programs
involving
the
use
of
dihalodialkylhydantoin­
containing
products
were
reviewed
to
determine
the
effects
of
exposure
to
dihalodialklhydantoins.
The
reported
routes
of
exposure
for
the
126
cases
were
dermal
(
44%),
ocular
(
25%),
ingestion
(
7%)
and
inhalation
(
43%).

°
Poison
Control
Centers
­
as
the
result
of
a
data
purchase
by
EPA,
OPP
received
Poison
Control
Center
data
covering
the
years
1993
through
1996
for
all
pesticides.
Most
of
the
national
Poison
Control
Centers
(
PCCs)
participate
in
a
national
data
collection
system,
the
Toxic
Exposure
Surveillance
System,
which
obtains
data
from
about
65­
70
centers
at
hospitals
and
universities.
PCCs
provide
telephone
consultation
for
individuals
and
health
care
providers
on
suspected
poisonings,
involving
drugs,
household
products,
pesticides,
etc.
All
the
incidences
reported
in
the
Poison
Control
Center
database
were
included
in
the
OPP's
IDS.
No
additional
data
were
reported
in
the
Poison
Control
Center
database
covering
the
years
1993­
1996.

°
California
Department
of
Pesticide
Regulation
­
California
has
collected
uniform
data
on
suspected
pesticide
poisonings
since
1982.
Physicians
are
required,
by
statute,
to
report
to
their
local
health
officer
all
occurrences
of
illness
suspected
of
being
related
to
exposure
to
pesticides.
The
majority
of
the
incidents
involve
workers.
Information
on
exposure
(
worker
activity),
type
of
illness
(
systemic,
eye,
skin,
eye/
skin
and
respiratory),
likelihood
of
a
causal
relationship,
and
number
of
days
off
work
and
in
the
hospital
are
provided.
Detailed
descriptions
of
28
cases
with
a
definite,
probable,
or
possible
relationship
to
dihalodialkylhydantoin
were
submitted
to
the
California
Pesticide
Illness
Surveillance
Program
and
reviewed.
All
the
reported
cases
were
occupational
related.
The
illness
types
were
classified
as
being
systemic
(
5
cases),
eye
(
16),
skin
(
8),
respiratory
(
12),
or
a
combination
of
the
types.

°
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.
No
incidences
were
reported
in
the
NPTN
database
Page
53
of
57
related
to
dihalodialklhydantoin
exposure.

°
Published
Incident
Reports
­
Several
papers
have
been
published
outlining
the
problems
associated
with
the
use
of
dihalodialklhydantoin.
The
chemical
1­
bromo­
3­
chloro­
5,5­
dimethylhydantoin
(
BCDMH),
one
of
four
dihalodialkylhydantoin.
BCDMH
is
commonly
used
as
an
alternative
to
chlorine
in
the
disinfection
of
swimming
pools.
Sodium
bromide
is
one
end
product
of
BCDMH
disinfection.
Several
case
studies
of
exposure
to
BCDMH
have
been
reported
in
the
literature
and
some
are
briefly
summarized
here:

°
A
survey
performed
in
1990
revealed
that
in
chlorinated
pools,
rashes
occurred
in
2
out
of
1.7
million
bathers,
while
in
BCDMH
pools,
rashes
occurred
in
43
out
of
31,000
bathers.
The
incidence
of
rashes
appears
to
occur
more
often
in
the
elderly
population;
approximately
20%
in
those
over
70
years
old
and
only
about
0.2%
in
those
under
20
years
old.
The
reaction
to
BCDMH
is
considered
to
be
an
irritant
contact
dermatitis,
rather
than
an
allergic
mechanism,
since
people
who
develop
rashes
do
not
test
positive
to
patch
tests
of
a
1%
solution
of
DiHalo
®
,
a
formulation
of
BCDMH
(
Penny,
1991).

°
Rycroft
and
Penny
(
1983)
reported
cases
happened
in
swimming
pools
in
United
Kingdom.
Nineteen
brominated
pools
were
visited
and
65
patients
with
rashes
were
seen.
In
one
swimming
pool,
it
was
estimated
that
at
least
5%
of
users
of
the
pools
had
experienced
itching
after
swimming
and
most
had
developed
rashes.

°
Penny
(
1999)
summarized
the
typical
features
of
a
BCDMH.
In
most
cases,
exposure
to
BCDMH
results
in
the
development
of
an
intensely
itchy
rash
which
starts
within
12
hours
of
the
exposure.
Progression
of
the
reaction
leads
to
widespread
dermatitis
of
varying
distributions
which
occasionally
include
lesions
and
can
be
associated
with
fever
and
malaise.
Re­
exposure
can
be
considerably
hazardous
especially
shortly
after
occurrence
of
the
rash
and
many
people
find
the
symptoms
so
severe
that
they
can
no
longer
swim
in
pools
treated
with
BCDMH.
In
some
cases,
people
who
develop
rashes
are
unable
to
return
to
chlorinated
pools,
which
suggests
a
cumulative
trauma
irritant
dermatitis.
It
is
believed
that
exposure
causes
the
skin
defenses
to
become
damaged
and
that
subsequent
exposure
to
weaker
irritants
may
then
cause
problems.

°
Morgan
(
1983)
reported
on
a
local
swimming
pool
which
had
changed
from
using
a
chlorine
disinfectant
to
DiHalo
®
.
After
the
switch
in
disinfectant,
121
people
developed
a
skin
reaction.
Seven
of
the
21
affected
were
children.

°
Malteen
et
al.
(
1985)
discussed
the
effects
of
exposure
to
Aquabrom,
an
antimicrobial
agent
used
in
indoor
swimming
pools.
Children
and
elderly
were
observed
to
develop
generalized
dermatitis
after
frequent
visits
to
the
pools.
Once
young
girl
exhibited
deviations
from
normal
resistance
values
after
her
forearm
skin
was
exposed
to
the
chemical
on
4
consecutive
days,
for
1
hour
per
day
at
a
.05%
concentration.
An
elderly
male
exhibited
both
decreased
resistance
and
water
vapor
loss
after
his
skin
was
exposed.
Clear
deviations
from
normal
were
also
Page
54
of
57
exhibited
by
the
elderly
male
subject
after
5
consecutive
days
of
1
hour
exposures
at
a
0.01%
concentration
of
Aquabrom
and
after
10
days
of
1
hour
exposure
at
a
0.002%
concentration
of
Aquabrom.
The
common
usage
concentration
was
reported
to
be
between
0.0003%
and
0.001%,
which
allows
for
a
narrow
safety
margin
between
the
concentration
used
here
which
produced
results
and
the
concentrations
normally
used.

°
Loughney
and
Harrison
(
1998)
report
a
case
on
a
46
year
old
physiotherapist
who
did
hydrotherapy
work
and
developed
an
intense
itching
and
redness
of
the
skin
after
exposure
to
the
swimming
pool
used
at
work.
The
itching
and
redness
progressed
into
a
persistent
itching
of
the
skin
with
a
generalized
dry
condition.
The
patient's
exposure
was
determined
to
be
3
sessions
per
week
in
the
pool
with
each
session
lasting
3
hours.
The
pool
was
disinfected
by
a
closed
dosing
system
with
a
bromine­
based
disinfectant.
Workplace
visits
and
interviews
with
the
staff
revealed
that
6
out
of
15
pool
users
had
mild
symptoms
of
skin
irritation
and
one
had
a
severe
case
of
eczema.

9.2
Epidemiological
Data
Associated
with
Chronic
Health
Effects
of
Halohydantoin
Exposure
There
are
no
epidemiological
data
that
can
be
located
associated
with
chronic
health
effects
due
to
halohydantoin
exposure.

10.0
Data
Gaps
82­
4/
870.3465
90­
Day
Inhalation
72­
4b/
850.1400
Invertebrate
life­
cycle
testing­
freshwater
TGAI1
123­
1/
850.4225
Seedling
emergence
dose
 
response
in
rice
TEP2
123­
1/
850.4250
Vegetative
vigor
dose­
response
in
rice
TEP
123­
2/
850.4400
Aquatic
vascular
plant
dose­
response
toxicity­
Lemna
sp.
TGAI
or
TEP
123­
2/
850.5400
Acute
algal
dose­
response
toxicity
­
4
species
TGAI
or
TEP
Page
55
of
57
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