INCIDENT
REPORTS
ASSOCIATED
WITH
HALOHYDANTOINS
(
PC
CODE:
006315,
006317,
115501,
115502,
028501,
and128826)

July
27,
2004
U.
S.
Environmental
Protection
Agency
Office
of
Pesticide
Programs
Antimicrobials
Division
TABLE
OF
CONTENTS
0.0
INTRODUCTION
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3
1.0
INCIDENT
REPORT
DATA
ASSOCIATED
WITH
HEALTH
EFFECTS
OF
HYDANTOIN
EXPOSURE
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3
1.1
OPP's
Incident
Data
System
(
IDS)
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4
1.2
Poison
Control
Center
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5
1.3
California
Data
­
1982
through
1996
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5
1.4
National
Pesticide
Telecommunications
Network
(
NPTN)
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6
1.5
Incident
Reports
Associated
with
Acute
Toxic
Effects
of
TEG
Published
in
Scientific
Literature.
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6
2.0
EPIDEMIOLOGICAL
DATA
ASSOCIATED
WITH
CHRONIC
HEALTH
EFFECTS
OF
HYDANTOIN
EXPOSURE
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8
3.0
SUMMARY
AND
CONCLUSION
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8
4.0
REFERENCES
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9
Page
3
of
9
0.0
INTRODUCTION
Hydantoins
are
antimicrobials
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.
The
dihalodialkylhydantoins
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
dimethyl­
hydantoin
and
1­
hydroxymethyl)­
5,5­
dimethylhydantoin).
The
purpose
of
this
chapter
is
to
review
the
evidence
of
health
effects
in
humans
resulting
from
exposure
to
dihalodialkylhydantoins.

Two
approaches
are
used
in
this
section:

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

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

This
reports
summarized
the
potential
health
effects
of
hydantoins
in
humans,
reported
as
incident
reports
from
different
sources.

1.0
INCIDENT
REPORT
DATA
ASSOCIATED
WITH
HEALTH
EFFECTS
OF
HYDANTOIN
EXPOSURE
The
following
databases
have
been
consulted
for
the
poisoning
incident
data
on
the
active
ingredient
dihalodialkylhydantoins
(
PC
Code:
006315,
006317,
115501,
115502,
028501,
and128826)

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

b.
Poison
Control
Centers
­
as
the
result
of
a
data
purchase
by
EPA,
OPP
received
Page
4
of
9
Poison
Control
Center
data
covering
the
years
1993
through
1998
for
all
pesticides.
Most
of
the
national
Poison
Control
Centers
(
PCCs)
participate
in
a
national
data
collection
system,
the
Toxic
Exposure
Surveillance
System,
which
obtains
data
from
about
65­
70
centers
at
hospitals
and
universities.
PCCs
provide
telephone
consultation
for
individuals
and
health
care
providers
on
suspected
poisonings,
involving
drugs,
household
products,
pesticides,
etc.

c.
California
Department
of
Pesticide
Regulation
­
California
has
collected
uniform
data
on
suspected
pesticide
poisonings
since
1982.
Physicians
are
required,
by
statute,
to
report
to
their
local
health
officer
all
occurrences
of
illness
suspected
of
being
related
to
exposure
to
pesticides.
The
majority
of
the
incidents
involve
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.

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

e.
Published
Incident
Reports
­
Some
incident
reports
associated
with
hydantoins
related
human
health
hazard
are
published
in
the
scientific
literature.

1.1
OPP's
Incident
Data
System
(
IDS)

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
dihalodialkylhydantoin.
The
reported
routes
of
exposure
for
the
126
incident
cases
were
dermal
(
44%),
ocular
(
25%),
ingestion
(
7%)
and
inhalation(
43%).
In
some
cases
more
than
one
route
of
exposure
applied
for
an
individual
incident
case
(
e.
g.,
both
dermal
and
ocular
exposure).

The
most
common
symptoms
reported
for
cases
of
dermal
exposure
were
skin
irritation/
burning
(
91%),
rash
(
36%),
itching
(
14%),
skin
discoloration/
redness
(
11%),
hives/
welts
(
9%),
blistering
(
7%),
allergic
reaction
(
5%),
and
bleeding
(
2%).
The
most
common
symptoms
reported
for
cases
of
ocular
exposure
were
eye
irritation/
burning
(
100%),
eye
pain
(
31%),
and
swelling
of
eyes
(
3%).

The
most
common
symptoms
reported
for
cases
of
inhalation
exposure
were
respiratory
irritation/
burning
(
70%),
irritation
to
mouth/
throat/
nose
(
33%),
coughing/
choking
(
24%),
shortness
of
breath
(
9%),
dizziness
(
4%),
flu­
like
symptoms
(
4%),
headache
(
4%),
seizure
(
2%),
Page
5
of
9
and
heart
palpitation
(
2%).

The
most
common
symptoms
reported
for
cases
of
ingestion
were
irritation
to
mouth/
throat/
nose
(
67%),
vomiting/
nausea/
abdominal
pain
(
11%).

1.2
Poison
Control
Center
All
the
incidences
reported
in
the
Poison
Control
Center
data
base
were
included
in
the
OPP's
IDS.
No
additional
data
were
reported
in
the
Poison
Control
Center
database
covering
the
years
1993
through
1996.

1.3
California
Data
­
1982
through
1998
Detailed
descriptions
of
28
cases
with
a
definite,
probable
or
possible
relationship
cases
submitted
to
the
California
Pesticide
Illness
Surveillance
Program
(
1982­
1998)
were
reviewed.
All
the
reported
cases
are
occupationally
related.
Table
4­
1
presents
the
types
of
illnesses
reported
by
year.
Table
4­
2
gives
the
total
number
of
workers
that
took
time
off
work
as
a
result
of
their
illness
and
how
many
were
hospitalized
and
for
how
long.

Table
4­
1.
Cases
Due
to
Dihalodialkylhydantoin
Exposure
in
California
Reported
by
Type
of
Illness
and
Year,
1982­
1998
Year
Illness
Type
Systemica
Eye
Skin
Respiratory
Combinationb
Total
1990
­
1
1
1
1
1
1991
5
8
1
7
7
13
1992
­
3
1
2
1
5
1993
­
­
1
­
­
1
1994
­
2
2
1
1
3
1995
­
­
1
­
­
1
1996
­
1
­
­
­
1
1997
­
­
­
1
­
1
1998
­
1
1
­
­
2
Page
6
of
9
Year
Illness
Type
Systemica
Eye
Skin
Respiratory
Combinationb
Total
Total
5
16
8
12
10
28
a
Category
include
cases
where
skin,
eye,
or
respiratory
effects
were
also
reported.
b
Category
includes
combined
irritative
effects
to
eye,
skin,
and
respiratory
system.

Table
4­
2:
Number
of
Persons
Disabled
(
taking
time
off
work)
or
Hospitalized
for
Indicated
Number
of
Days
After
Dihalodialkylhydantoin
Exposure
in
California,
1982­
1996.

Number
of
Persons
Disabled
Number
of
Persons
Hospitalized
One
day
1
­

Two
days
­
­

3­
5
days
­
­

6­
10
days
1
­

more
than
10
days
­
­

Unknown
2
­

1.4
National
Pesticide
Telecommunications
Network
(
NPTN)

There
are
no
incident
reported
in
the
NPTN
database
related
to
dihalodialkylhydantoin
exposure.

1.5
Incident
Reports
Associated
with
Acute
Toxic
Effects
of
Hydantoins
Published
in
Scientific
Literature.

Several
papers
have
been
published
outlining
the
problems
associated
with
the
use
of
dihalodialkylhydantoin.
The
chemical
1­
bromo­
3­
chloro­
5,5­
dimethlyhydantoin
(
BCDMH),
one
of
four
dihalodialkylhydantoins,
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
Page
7
of
9
million
bathers
(
1.2
per
million),
while
in
BCDMH
pools,
rashes
occurred
in
43
out
of
31,000
(
1,387
per
million)
annual
bathers
(
Penny,
1991).
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.

Rycroft
and
Penny
(
1983)
reported
cases
that
happened
in
swimming
pools
in
the
United
Kingdom.
Nighteen
brominated
pools
were
visited.
After
visiting
19
swimming
pools
treated
with
BCDMH,
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
Di­
Halo
(
the
active
ingredient
is
BCDMH)
.
After
the
switch
in
disinfectant,
21
people
developed
a
skin
reaction.
Seven
of
the
21
affected
were
children.

Malten
et
al.
(
1985)
discussed
the
effects
of
exposure
to
Aquabrom,
an
antimicrobial
agent
containing
dihalodialkylhydantoin
used
in
indoor
swimming
pools.
Children
and
elderly
were
observed
to
develop
generalized
dermatitis
after
frequent
visits
to
the
pools.
One
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
0.05%
concentration.
An
elderly
male
exhibited
both
decreased
resistance
and
water
vapor
loss
after
his
skin
was
exposed.
Clear
deviations
from
normal
were
also
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
effects
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
Page
8
of
9
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.

2.0
EPIDEMIOLOGICAL
DATA
ASSOCIATED
WITH
CHRONIC
HEALTH
EFFECTS
OF
HYDANTOIN
EXPOSURE
There
is
no
epidemiological
data
that
can
be
located
associated
with
the
chronic
health
effects
of
dihalodialkylhydantoins
exposure.

3.0
SUMMARY
AND
CONCLUSION
There
are
many
incident
reported
associated
with
exposure
to
end­
use
products
containing
dihalodialkylhydantoins.
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
and
blistering.
Allergic
type
reactions
including
hives/
welts,
allergic
contact
dermatitis,
and
bleeding
have
also
been
reported..
The
most
common
symptoms
reported
for
cases
of
ocular
exposure
were
eye
irritation/
burning.
Eye
pain
and
swelling
of
eyes
also
have
been
reported
in
some
incidents.

The
most
common
symptoms
reported
for
cases
of
inhalation
exposure
were
respiratory
irritation/
burning,
irritation
to
mouth/
throat/
nose,
coughing/
choking,
shortness
of
breath,
dizziness,
flu­
like
symptoms,
and
headache.

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.

There
is
no
epidemiological
data
that
can
be
located
associated
with
chronic
health
effects
of
dihalodialkylhydantoins
exposure.
Page
9
of
9
4.0
REFERENCES
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R.
J.
and
Penny,
P.
T.
1983.
Dermatosis
associated
with
brominated
swimming
pools.
Br.
Med.
J.
287:
462.

Loughney,
L.
and
Harrison,
J.
1998.
Irritant
contact
dermatitis
due
to
1,
bromo­
3­
chloro­
5,5­
dimentylhydantoin
in
a
hydrotherapy
Pool.
Risk
assessment:
the
need
for
continuous
evidence­
based
assessment.
Occup.
Med.
48:
461­
463
Morgan,
J.
M.
1983.
Dermatoses
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brominated
swimming
pools.
Br.
Med.
J.
287:
913.

Gould,
D.
J.
1983.
Dermatoses
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Br.
Med.
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287:
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Malten
K.
E.
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J.
A.
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Penny,
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1991.
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