MEMORANDUM
September
7,
2004
Subject:
Environmental
Fate
Assessment
of
Hydantoins
To:
Ben
Chambliss,
Acting
Team
Leader,
Team
32
Regulatory
Management
Branch
II
Antimicrobials
Division
(
7510C)

From:
A.
Najm
Shamim,
Ph.
D.,
Chemist
Regulatory
Management
Branch
II
Antimicrobials
Division(
7510C)

Thru:
Connie
Welch,
Chief
Regulatory
Management
Branch
II
Antimicrobials
Division
(
7510C)

And
Sanyvette
Williams,
Science
Coordinator
for
Hydantions
RED
Antimicrobials
Division
(
7510C)

Enclosed
if
the
Science
Chapter
on
the
Environmental
Fate
Assessment
on
Hydantoins
for
reregistration
considerations.
Page
2
of
6
SCIENCE
ASSESSMENT
Environmental
Fate
a.
Environmental
Fate
Assessment
The
Agency
does
not
have
a
complete
database
for
environmental
fate
studies
on
hydantoins.
However,
hydrolysis
appears
to
be
the
major
route
for
dissipation
of
Halobrom
7
(
1­
Bromo­
3­
chloro­
5,5­
dimethylhydantoin).
Halobrom
7
has
been
shown
to
hydrolyze
relatively
rapidly.
It
also
degrades
rapidly
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
Halobrom
7
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.
An
aqueous
photolytic
study
on
dimethylhydantoin,
conducted
at
pH
7
and
at
25

1
o
C
in
the
presence
of
xenon
arc
as
light
source,
yielded
a
first
order
rate
constant
of
7.89
x10­
4
/
day
which
translates
into
a
half
life
of
878
days.
Aqueous
photolytic
stability
means
that
surface
water
run­
off
can
of
DMH
can
be
a
source
of
concern
for
drinking
water
contamination.
The
Agency
lacks
any
data
on
hydantoins
as
far
as
mobility
(
soil
column
leaching)
is
concerned,
as
well
as
binding
constants
to
soils
(
Kd
s)
to
indicate
if
hydantoins
will
be
persistent
in
soils.
Because
of
lack
of
data,
the
Agency
can
not
assess
if
hydantoins
are
bioaccumulative
and
if
these
can
a
source
of
concern
for
the
aquatic
organisms.

b.
Environmental
Fate
and
Transport
Halobrom
7
degrades
relatively
rapidly
in
water
under
abiotic
conditions.
However,
there
is
environmental
concern
for
soil
or
surface
water
contamination
from
the
major
degradate
DMH
(
dimethylhydantoin),
as
DMH
is
hydrolytically
and
photolytically
stable.
No
additional
fate
data
on
dimethylhydtanoins
are
available
to
further
assess
fate
of
this
chemical.
Page
3
of
6
APPENDIX
I
Abiotic
Degradation
Hydrolysis
Two
hydrolysis
studies
were
submitted
and
were
reviewed;
one
hydrolysis
study
was
conducted
with
Halobrom
7
as
the
test
chemical
and
the
other
study
was
conducted
with
DMH
as
the
test
chemical.
Imidazolidine
ring­
labeled
[
5­
14C]
Halobrom
7,
at
nominal
concentrations
of
90.9
mg/
L
(
pH
5)
and
90.0
mg/
L
(
pH
7
and
pH
9)
hydrolyzed
with
respective
registrant­
calculated
half­
lives
of
885
hours,
69.5
hours,
and
72.4
hours
in
pH
5,
pH
7,
and
pH
9
aqueous
buffer
solutions
incubated
in
darkness
at
25

1

C
for
718.5
hours
(
pH
5),
336
(
pH
7),
and
337
hours
(
pH
9).
The
registrant­
calculated
half­
lives
at
all
pH
levels
were
overestimated
because
they
were
based
on
the
initial
concentration
of
the
parent
in
solution
rather
than
a
nominal
concentration.
Instantaneous
hydrolysis
of
the
parent
compound
was
observed
during
the
preparation
of
the
test
solutions.
As
such,
at
the
initiation
of
the
incubation
period
(
time
0),
the
parent
compound
was
present
in
the
pH
5,
pH
7,
and
pH
9
systems
at
mean
concentrations
of
70.6
mg/
L,
77.7
mg/
L,
and
72.3
mg/
L,
respectively.
Based
on
these
nominal
application
rates,
the
apparent
half­
lives
were
between
525.5
to
694.5
hours
for
the
pH
5
system,
49
to
72.5
hours
for
the
pH
7
system,
and
10
to
27
hours
for
the
pH
9
system.
By
the
end
of
the
incubation
period,
the
concentration
of
the
parent
in
the
pH
5
and
pH
7
systems
decreased
to
39.2
mg/
L
and
2.3
mg/
L,
respectively.
The
concentration
of
the
parent
at
the
end
of
the
incubation
period
for
the
pH
9
buffer
was
less
than
the
limit
of
quantitation
(
LOQ).
DMH
(
dimethylhydantoin),
as
a
percent
of
recovered
radioactivity,
increased
in
all
buffer
systems
from
time
0
(
11.3%
to
24.5%)
to
the
end
of
the
incubation
period
(
50.7%,
97.6%,
100%
for
the
pH
5,
pH
7,
and
pH
9
buffer
systems,
respectively).

In
the
hydrolysis
study
of
DMH,
nonradiolabeled
plus
imidazolidine
ring­
labeled
[
5­
14C]
DMH,
at
a
nominal
concentration
of
10

g/
mL,
was
hydrolytically
stable
in
sterile
pH
5,
pH
7,
and
pH
9
aqueous
buffer
solutions,
which
were
incubated
in
darkness
at
25

1

C
for
up
to
30
days.
Following
the
incubation
period,
the
parent
compound
was
present
in
the
four
buffer
solutions
at
95.7%
(
pH
5),
92.3%
(
pH
7,
TRIS),
94.7%
(
pH
7,
HEPES),
and
94.8%
(
pH
9)
of
the
applied
radioactivity.
The
solubility
of
the
test
compound
in
each
of
the
buffer
solutions
was
not
reported.
As
such,
it
could
not
be
determined
whether
the
compound
was
available
in
solution
for
hydrolytic
degradation.
Both
studies
were
found
acceptable
(
MRID#
s:
432818­
01,
424662­
01)

In
the
aqueous
photolytic
study,
radiolabeled
dimethylhydantoin
(
DMH)
at
pH
7
and
under
buffer
conditions
(
HEPES
buffer),
was
subjected
to
xenon
light
at
25
o
C.
the
study
was
carried
out
for
30
days..
No
significant
degradation
was
observed
for
exposed
(
to
xenon
light)
and
non­
exposed
samples.
The
percentages
of
total
radioactivity
reocvery
was
94.2%
for
the
xenon­
exposed
samples
and
96.4%
for
nonexposed
samples.
For
the
xenon­
exposed
radiolabeled
samples,
the
photolytic
first
order
rate
constant
was
determined
as
7.89
x10­
4/
day
and
half
life
from
this
value
comes
out
to
be
878
days.
Dimethylhydantoin
(
DMH)
shows
no
tendency
to
breakdown
under
photolytic
conditions
in
water
at
pH
7.
The
study
was
acceptable
(
MRID#:
424662­
02)
Page
4
of
6
Page
5
of
6
II
Biotic
Degradation
Anaerobic
Aquatic
Metabolism
In
an
anaerobic
aquatic
metabolism
study
imidazolidine
ring­
labeled
[
5­
14C]
Halobrom
7,
at
a
nominal
concentration
of
101
mg/
mL,
degraded
rapidly
with
an
observed
half­
life
of
less
than
4
hours
in
an
anaerobic
flooded
silty
clay
sediment
that
was
incubated
with
a
nitrogen
purge
in
darkness
at
a
mean
temperature
of
24.1

C.
The
samples
were
incubated
for
up
to
12
months.
In
the
water
phase,
the
parent
compound
was
initially
(
time
0)
present
at
12.8%
of
the
applied
radioactivity
and
was
last
detected
at
1.5%
after
four
hours.
The
parent
compound
was
not
present
in
the
sediment
phase
at
any
of
the
sampling
intervals.
Accordingly,
the
short
half­
life
of
the
parent
compound
appeared
to
be
independent
of
aerobic
or
anaerobic
conditions.
The
study
also
indicated
that
hydrolysis
is
an
early
step
in
the
degradation
process
and
is
the
major
degradation
route
for
Halorbrom.
The
study
was
found
acceptable
(
MRID#:
427384­
01).
The
major
degradate,
DMH,
was
initially
(
time
0)
present
in
the
water
phase
at
87.6%
of
the
applied
radioactivity
and
increased
to
a
maximum
of
93.3%
of
the
applied
radioactivity
by
4
hours
posttreatment.
Between
6
days
and
12
months,
DMH
present
in
the
water
phase
ranged
from
62.8%
and
72.1%
of
the
applied
radioactivity.
In
the
sediment
phase,
DMH
was
initially
(
time
0)
present
at
2.7%
of
the
applied
radioactivity
and
increased
to
a
maximum
of
19.2%
of
the
applied
radioactivity
by
day
6.
At
12
months,
13.1%
of
the
applied
radioactivity
was
present
in
the
sediment.
An
unidentified
degradate
was
also
detected
sporadically
in
the
water
and
sediment
phases
at
up
to
8.8%
of
the
applied
radioactivity.

Total
[
14C]
residues
were
measured
in
the
interstitial
water,
but
were
not
characterized
for
the
parent
compound
or
degradates.
Total
[
14C]
residues
in
the
interstitial
water
were
initially
1.9%
of
the
applied
and
increased
to
a
maximum
of
11.5%
of
applied
by
day
13.
Between
9
and
12
months,
the
total
[
14C]
residues
in
the
interstitial
water
were
between
6.9%
and
7.0%
of
the
applied
radioactivity.
Total
radiolabeled
[
14C]
volatiles
were
also
measured;
however,
the
percent
of
applied
was
negligible.
Throughout
the
incubation
period,
the
majority
of
the
[
14C]
residues
were
observed
in
the
water
phase.
The
distribution
ratio
of
[
14C]
residues
between
the
water
and
sediment
phases
were
not
reported.
Page
6
of
6
Bibliography
1.
US
EPA
MRID#:
427384­
01
2.
US
EPA
MRID#:
424662­
02
3.
US
EPA
MRID#:
432818­
01
4.
US
EPA
MRID#:
424662­
01
