UNITED
STATES
ENVIRONMENTAL
PROTECTION
AGENCY
WASHINGTON,
D.
C.
20460
OFFICE
OF
PREVENTION,
PESTICIDES
AND
TOXIC
SUBSTANCES
MEMORANDUM
DATE:
05/
08/
2003
SUBJECT:
[
Dimethylhydantoin]
[
Acute,
Probabilistic,
Chronic,
Cancer]
Dietary
Exposure
Assessment[
s]
for
the
[
Section
(
3,
18)
Reregistration
Eligibility
Decision,
etc.]

PC
Code:
115501
DP
Barcode:
n/
a
REVIEWER:
A.
Najm
Shamim
Ph.
D,
Chemist
Antimicrobials
Division
(
7510C)

THROUGH:
A.
Najm
Shamim,
Ph.
D.,
Chemist,
Name
of
Detailed
Reviewer,
Title
Antimicrobials
Division
(
7510C)

and
Tim
McMahon,
Ph.
D.,
Senior
Toxicologist,
Antimicrobials
Division
(
7510C)

TO:
Connie
Welch,
Chief,
Regulatory
Management
Branch
II
Antimicrobials
Division
(
7510C)
Page
2
of
18
Executive
Summary
The
purpose
of
this
memorandum
is
to
report
the
results
of
a
dietary
exposure
analysis
for
Hydantoins.
These
chemicals
are
diazines
of
five­
membered
ring.
Substitution
can
be
made
on
positions
1
and
3
with
halogens
or
any
other
functional
group(
s)
like
hydroxy
methyl
or
bis
(
1,3­
dihydroxy
methyl)
moities,
or
by
dimethyl
or
ethylmethyl
groups.
These
antimicrobials
are
registered
for
use
in
indoor
food,
in­
door
non­
food,
indoor
industrial
sites
for
control
of
bacteria,
fungi
and
algal
slimes.
Indoor
food
use
arises
from
the
use
of
these
chemicals
in
food­
contact
paper
and
paperboards
where
the
mixture
of
these
substances
are
used
as
slimicide,
filler
preservative
and
coating
preservative.
In
this
analysis
the
[
acute,
chronic,
and/
or
cancer]
dietary
exposure
and
risk
estimates
resulting
from
food
intake
were
determined
for
the
general
U.
S.
population
and
various
population
subgroups.
For
reregistration
actions:
[
Acute,
chronic,
cancer]
dietary
exposure
assessments
were
performed
in
order
to
determine
the
exposure
and
risk
estimates
which
result
from
the
use
of
[
dimethylhydantoin]
as
slimicide,
filler
preservative
and
filler
for
inorganic
slurries,
coating
preservative
in
food
contact­
paper
and
paperboard
which
is
included
in
the
reregistration
eligibility
decision.

°
Briefly
describe
the
assumptions
that
went
into
the
assessment,
using
language
from
AD's
approach
for
conducting
dietary
exposure
and
risk
analyses.
°
Provide
an
overview
of
the
level
of
refinement
used
in
the
assessment.

The
[
acute
and/
or
chronic]
dietary
analyses
for
[
chemical]
show
that....

°
Discuss
the
results
of
the
analyses.
State
whether
or
not
the
results
are
above
or
below
AD's
level
of
concern
(
note:
HED's
level
of
concern
(
i.
e.
<
100%
PAD)
should
not
be
defined
in
the
Executive
Summary.
It
will
be
defined
in
the
Introduction.).
Provide
the
results
for
the
general
U.
S.
population
and
the
most
highly
exposed
population
subgroup.
For
the
acute
analysis,
state
at
which
percentile
of
exposure
the
results
are
being
reported.

The
cancer
dietary
exposure
estimate
for
the
general
U.
S.
population
is
(
X.
X
x
10­
x),
which
is
[
above/
below]
AD's
level
of
concern.


If
the
risk
is
above
AD's
level
of
concern,
provide
brief
discussion
of
how/
if
the
risk
estimate
could
be
refined
I.
Introduction
AD's
label
search
has
shown
that
hydantoins
are
mixtures
of
dimethyl
and
or
methyl,
ethyl
halogenated
hydantoins
where
halgenation
can
be
either
dichloro,
or
dibromo
or
chloro/
bromo
isomers.
In
addition,
hydroxymethyldimethyl
hydantoin
and
or
bisdihydroxymethyldimethyl
hydantoin
have
been
added
to
the
list
for
which
dietary
exposure
assessment
is
being
conducted.
Three
major
indirect
food
contact
scenarios
emerge
from
the
use
of
Dantogard
and
these
are:
Page
3
of
18
1)
Use
as
a
slimicide
in
paper
and
paperboard
manufacturing
process;
2)
filler
preservative
use
in
food
and
non­
food
contact
paper
and
paper
board.
These
fillers
are
made
of
inorganic
slurries
used
for
food­
contact
paper
and
paperboard;
3)
Use
as
a
coating
preservative
for
food
contact
paper
and
paperboard.
Moreover,
uses
of
hydantoins
as
disinfectant
in
swimming
pools,
and
in
industrial
once­
through
cooling
water
systems
as
well
as
recirculating
cooling
water
systems1
are
established
but
are
not
included
in
the
present
risk
assessment.
(
AD's
Memo
by
A.
Najm
Shamim
on
label
reviews
for
hydantoins,
March
2003).

For
Reregistration
Eligibility
Decision
(
RED)
process
the
Agency
has
carried
out
the
dietary
exposure
and
risk
assessments
of
hydantoins.
This
includes,
besides
the
halogenated
dimethylhydantoins
,
methylhydroxydimethylolhydantoin
and
bisdimethylhydroxydimethylhydantoins
In
1989,
the
Agency
agreed
to
clustering
of
the
hydantoins
into
one
set
and
allowed
the
toxicity
studies
to
be
conducted
on
dimethylhydantoin,
which
would
represent
the
cluster
of
hydantoins
(
HED
Memo
by
Joycelyn
Stewart,
August,
1989)
2.
Further
search
of
chemical
data
indicates
that
in
particular,
methylhydroxyhydantoins
emit
formaldehyde
as
a
breakdown
product.
The
toxicity
or
dietary
risk
assessment
of
hydantoins,
therefore,
should
include
assessment
on
hydantoins
and
methylhydorxyhydantoins
Residue
Chemistry:

Due
to
the
unique
use
of
these
chemicals,
no
residue
chemistry
data
were
submitted
by
registrants
(
Residue
Chemistry
Guidelines
#.
OPPTS
GLN
860.1300,
OPPTS
GLN
860.1340,
OPPTS
GLN
860.1500)
nor
was
asked
by
the
Agency.
For
reregistration
purposes
of
this
chemical,
there
are
no
residue
chemistry
issues.

Dietary
Exposure:

The
Agency
has
used
available
methods
to
estimate
hydantoin
residues
on
food
due
to
migration
of
these
chemicals
or
their
breakdown
products,
when
these
substances
come
into
contact
with
food­
contact
paper
and
paperboard.
In
this
regard
Food
and
Drug
Administration
has
developed
guidelines
to
estimate
the
residues
of
pesticides
used
as
slimicides
etc.
and
their
migration
onto
food
through
surface
contact
(
called
indirect
food
contact).
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
to
conduct
dietary
risk
assessment
Dietary
risk
assessment
incorporates
both
exposure
and
toxicity
of
a
given
pesticide.
For
acute
and
chronic
assessments,
the
risk
is
expressed
as
a
percentage
of
a
maximum
acceptable
dose.
This
is
the
population
adjusted
dose
(
PAD),
which
AD
has
concluded
will
result
in
no
unreasonable
adverse
health
effects.
The
PAD
is
the
Reference
Dose
(
RfD)
divided
by
the
special
FQPA
Safety
Factor.
Dietary
risk
is
expressed
as
a
percentage
of
the
PAD.
For
acute
and
noncancer
chronic
exposures,
AD
is
concerned
when
estimated
dietary
risk
exceeds
100%
of
the
PAD.
AD
is
generally
concerned
when
estimated
cancer
risk
exceeds
one
in
one
million
(
i.
e.,
the
risk
exceeds
1
x
10­
6).
References
which
discuss
the
acute
and
chronic
risk
assessments
in
more
Page
4
of
18
detail
are
available
on
the
EPA/
pesticides
web
site:
"
Available
Information
on
Assessing
Exposure
from
Pesticides,
A
User's
Guide",
6/
21/
2000,
web
link:
http://
www.
epa.
gov/
fedrgstr/
EPA­
PEST/
2000/
July/
Day­
12/
6061.
pdf
;
or
see
SOP
99.6
(
8/
20/
99).

The
most
recent
dietary
risk
assessment
for
[
chemical]
was
conducted
by
[
name]
(
date,
DP
Barcode).

II.
Residue
Information
Review
of
the
Agency's
residue
chemistry
database
does
not
show
any
residues
on
food
or
on
any
RACs.
hence
no
residue
chemistry
data
and
analyses
are
included
in
this
dietary
exposure
chapter.

[
Dimethylhydantoins]
Use:


Include
the
CFR
Reference.
if
applicable

State
the
residue(
s)
of
concern,
if
applicable
°
Brief
discussion
of
tolerances
currently
in
effect
(
permanent
as
well
as
time­
limited),
if
applicable

Brief
discussion
of
pending
tolerances/
Section
18
time­
limited
tolerances,
if
applicable

If
applicable,
briefly
describe
how
the
metabolites
were
accounted
for
in
the
assessments,
and
the
rationale.


Summarize
reassessed
tolerances
(
include
or
refer
to
date
of
completed
RED
chapter
or
AR
assessment).
Note
general
differences
in
reassessed
vs.
established
tolerances,
especially
if
there
are
significant
changes
in
foods
which
comprise
a
substantial
portion
of
the
diets
of
infants
and
children.

The
following
section
should
be
included
only
if
applicable,
that
is,
if
an
antimicrobial
use
is
agricultural
related.

III.
DEEM­
FCID
 
Program
and
Consumption
Information
[
Chemical
name]
acute
and
chronic
dietary
exposure
assessments
were
conducted
using
the
Dietary
Exposure
Evaluation
Model
software
with
the
Food
Commodity
Intake
Database
(
DEEM­
FCID
 
,
Version
1.3),
which
incorporates
consumption
data
from
USDA's
Continuing
Surveys
of
Food
Intakes
by
Individuals
(
CSFII),
1994­
1996
and
1998.
The
1994­
96,
98
data
are
based
on
the
reported
consumption
of
more
than
20,000
individuals
over
two
non­
consecutive
survey
days.
Foods
"
as
consumed"
(
e.
g.,
apple
pie)
are
linked
to
EPA­
defined
food
commodities
(
e.
g.
apples,
peeled
fruit
­
cooked;
fresh
or
N/
S;
baked;
or
wheat
flour
­
cooked;
fresh
or
N/
S,
baked)
using
publicly
available
recipe
translation
files
developed
jointly
by
USDA/
ARS
and
EPA.
Consumption
data
are
averaged
for
the
entire
U.
S.
population
and
within
population
subgroups
for
chronic
exposure
assessment,
but
are
retained
as
individual
consumption
events
for
acute
exposure
assessment.

For
chronic
exposure
and
risk
assessment,
an
estimate
of
the
residue
level
in
each
food
or
Page
5
of
18
food­
form
(
e.
g.,
orange
or
orange
juice)
on
the
food
commodity
residue
list
is
multiplied
by
the
average
daily
consumption
estimate
for
that
food/
food
form.
The
resulting
residue
consumption
estimate
for
each
food/
food
form
is
summed
with
the
residue
consumption
estimates
for
all
other
food/
food
forms
on
the
commodity
residue
list
to
arrive
at
the
total
average
estimated
exposure.
Exposure
is
expressed
in
mg/
kg
body
weight/
day
and
as
a
percent
of
the
cPAD.
This
procedure
is
performed
for
each
population
subgroup.

For
acute
exposure
assessments,
individual
one­
day
food
consumption
data
are
used
on
an
individual­
by­
individual
basis.
The
reported
consumption
amounts
of
each
food
item
can
be
multiplied
by
a
residue
point
estimate
and
summed
to
obtain
a
total
daily
pesticide
exposure
for
a
deterministic
(
Tier
1
or
Tier
2)
exposure
assessment,
or
"
matched"
in
multiple
random
pairings
with
residue
values
and
then
summed
in
a
probabilistic
(
Tier
3/
4)
assessment.
The
resulting
distribution
of
exposures
is
expressed
as
a
percentage
of
the
aPAD
on
both
a
user
(
i.
e.,
those
who
reported
eating
relevant
commodities/
food
forms)
and
a
per­
capita
(
i.
e.,
those
who
reported
eating
the
relevant
commodities
as
well
as
those
who
did
not)
basis.
In
accordance
with
HED
policy,
per
capita
exposure
and
risk
are
reported
for
all
tiers
of
analysis.
However,
for
tiers
1
and
2,
significant
differences
in
user
vs.
per
capita
exposure
and
risk
are
identified
and
noted
in
the
risk
assessment.

IV.
Toxicological
Information
Include
general
background
information
about
the
chemical
as
necessary.


Provide
dates
of
relevant
AD
and
HED
memoranda,
such
as
the
reports
of
the
HIARC,
FQPA
SFC,
ADTOX,
and
Cancer
SARCs.


Include
the
toxicological
endpoint
summary
table
from
the
HIARC
document.
Delete
the
non­
dietary
exposure
scenarios.
In
the
event
that
the
summary
table
has
not
been
prepared,
the
table
below
can
be
used
as
a
guide.
The
table
should
clearly
indicate
the
LOAEL
and
NOAEL,
the
toxic
effect
observed
(
e.
g.,
weight
loss,
cholinesterase
inhibition,
etc.),
the
study
type
(
e.
g.,
oral,
dog),
and
the
uncertainty
factors
(
UFs)
applied
to
obtain
the
acute
and
chronic
reference
doses
(
aRfD
and
cRfD,
respectively),
and
the
acute
and
chronic
population
adjusted
doses
(
aPAD
and
cPAD,
respectively).


If
the
chemical
is
a
carcinogen,
note
the
classification
and
the
risk
assessment
approach
to
be
used,
and
the
Q
1
*
if
applicable.

Table
X.
Summary
of
Toxicological
Doses
and
Endpoints
for
[
CHEMICAL]
for
Use
in
Dietary
Exposure
Assessment
Exposure
Scenario
Dose
Used
in
Risk
Assessment,
UF
FQPA
SF*
and
Endpoint
for
Risk
Assessment
Study
and
Toxicological
Effects
Acute
Dietary
General
US
pop.
NOAEL
=
[
]
mg/
kg/
day
UF
=
[
]
Acute
RfD
=
[
]
mg/
kg/
day
FQPA
SF
=
[
]
aPAD
=[
]

=
[
]
mg/
kg/
day
[
insert
study
name]
LOAEL
=
[
]
mg/
kg/
day
based
on
[
]
Page
6
of
18
Table
X.
Summary
of
Toxicological
Doses
and
Endpoints
for
[
CHEMICAL]
for
Use
in
Dietary
Exposure
Assessment
Exposure
Scenario
Dose
Used
in
Risk
Assessment,
UF
FQPA
SF*
and
Endpoint
for
Risk
Assessment
Study
and
Toxicological
Effects
Acute
Dietary
[
population
subgroups]
NOAEL
=
[
]
mg/
kg/
day
UF
=
[
]
Acute
RfD
=
[
]
mg/
kg/
day
FQPA
SF
=
[
]
aPAD
=[
]

=
[
]
mg/
kg/
day
[
insert
study
name]
LOAEL
=
[
]
mg/
kg/
day
based
on
[
]

Chronic
Dietary
all
populations
NOAEL=
[
]
mg/
kg/
day
UF
=
[
]
Chronic
RfD
=
[
]
mg/
kg/
day
FQPA
SF
=
[
]
cPAD
=[
]

=
[
]
mg/
kg/
day
[
insert
study
name]
LOAEL
=
[
]
mg/
kg/
day
based
on
[
]

Cancer
Q*
=

V.
Results/
Discussion
FDA
Methodology
for
Determining
Estimated
Daily
Intake
(
EDI)
of
a
Pesticide
Used
As
a
Slimicide,
Filler
Preservative,
and
as
Coating
Preservative
On
Food
Contact
Paper
and
Paperboard.

AD
has
reviewed
FDA
Guidance
on
Food
Contact
Surfaces
and
related
documents3,4,5,6,7
and
a
summary
of
the
methodology/
technique
is
provided:

Some
assumptions
are
made
in
the
FDA
calculations
for
the
food
contact
surfaces
and
migration
of
the
active
into
food
from
the
food
contact
surfaces.:
1.
Food
contact
surface
(
paper
in
our
case)
could
be
a
one
time
use/
day
or
repeat
use
material/
day.
2.
Consumption
factor
(
CF)
or
fraction
of
the
daily
food
that
comes
into
contact
with
the
packaging
surface
(
paper
in
our
case).
CF
is
actually
the
weight
of
food
that
comes
into
contact
with
the
packaging
material
to
the
weight
of
all
food
packaged
with
the
packaging
material
(
paper
in
our
case).
The
CF
varies
from
one
packaging
material
to
the
other.
4.
FDA
calculations
assume
active
material
present
in
the
food
contact
surface
migrates
out
100%
(
this
represents
a
worst
case
scenario).

I.
Data
Input
Parameters
for
Hydantoins
Used
as
Slimicide
in
Paper
V.
Rate
of
Application:
Maximum
level
of
2
lbs.
Hydantoins/
ton
of
paper
(
it
also
means
1
kg
of
active/
1000
kg
of
paper.

2.
Paper
slurry:
Prior
to
entering
paper
manufacturing
machine:
1%
(
99%
water
and
1%
pulp)

3.
Concentration
of
Slurries
entering
Driers:
33%
pulp
and
67%
water
Page
7
of
18
4.
Standard
Paper
Weight:
50
mg/
in2.

5.
Finished
Paper:
8%
water
and
92%
pulp8
(
RASSB
Memo
by
Bob
Quick)

6.
Mass
of
Food
in
Contact
With
Surface
Area
of
Treated
paper:
10
gm.
Food/
in2.

7.
Consumption
Factor
(
CF)
for
Treated
paper:
0.10
8.
Daily
Average
food
in
take
(
adult)
=
3
kg.

9.
Daily
Average
food
Intake
(
child)
=
1500
g.

Calculations:

I.
Assume
the
active
is
98%
and
from
input
parameters
1
&
2:
1.96
lbs/
ton
of
paper
~
2
lbs/
ton
of
paper
=
200,000
lbs
slurry
x
1%
paper
slurry
=
2
lbs/
2000
lbs
finished
paper
=
10
ppm
of
active
in
the
paper
slurry.

Output:

Concentration
of
DMH
in
Paper/
Pulp:

1a.
From
input
parameter
3,
the
concentration
of
the
active
present
in
the
pulp
prior
to
entering
the
driers:
Appl.
Rate
x
%
water/%
pulp
=
10
ppm
DMH
=
10
µ
g
DMH/
gm
pulp
slurry
x
0.67
gm
water/
0.33
gm
pulp
=
20
µ
g
active/
gm
pulp­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­
i
Based
on
input
parameters
(
1­
7)
and
calculations
a
and
b,
the
outputs
are:

1b..
Concentration
of
Hydantoins
in
Food:

µ
g
of
active/
mass
of
pulp
x
mass
of
pulp/
mass
of
paper
x
standard
mass
of
paper
x
mass
of
food/
surface
area.
­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­
i
=
20
µ
g
active/
mass
of
pulp
x
0.92
gm
pulp/
gm
of
paper
x
0.05
gm/
in2
x
1
in2/
10
gm
food
=
0.092
µ
g
of
active/
gm
food.
­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­
ii
Taking
into
account
the
CF
of
0.10,
the
actual
dietary
concentration
of
hydantoins
in
daily
diet
would
be:
0.092
µ
g
active/
gm
food
x
0.10
=
0.0092
µ
g
of
DMH/
gm
of
food.­­­­­­­
iii
Environmental
fate
studies
(
see
environmental
fate
assessment
chapter,
A.
Najm
Shamim)
have
shown
that
the
halogenated
hydantoins
are
not
stable
in
aqueous
system
and
major
breakdown
product
is
dimethylhydantoin.
Ratio
of
MW
of
dimethylhydantoin/
to
average
MWs.
of
halogen­
containing
dimethylhydantoins
is
0.59.
Hence
if
we
multiply
(
ii)
with
0.59
=
0.0054
µ
g
DMH/
gm
food
is
the
concentration
in
the
daily
diet
­­­­­­­­­­­­­­­­­­­­­­­­
iv
In
most
of
the
formulations,
the
Agency
has
noted
that
10%
of
each
formulation
contains
Page
8
of
18
1,3­
dichloro­
5­
ethyl­
5­
methylhydantoin.
Hence
daily
diet
burden
shown
in
equation
(
iii)
contains
contributions
from
the
ethyl/
methyl
isomer,
that
is
10%
of
0.0054
µ
g
dmh/
gm,
the
actual
concentration
of
dmh/
gm
of
food
is:
0.0054
µ
g
dmh/
gm
food
­
0.00054
µ
g/
gm
food:
=
0.0049
µ
gdmh/
gm
food
present
in
the
daily
diet
­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­
v
Concentration
of
Formaldehyde
in
Food:

4.9
ppb
x
30
MW
formaldehyde/
128
MW
DMH
:
=
1.14
ppb
­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­
vi
1b.
Estimated
Daily
Intake
(
EDI)
of
DMH
For
An
Adult
=
0.0049
µ
g
of
DMH/
gm
food
x
3000gm
food
=
14.7
µ
g
DMH/
person/
day
­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­
vii
1c.
Estimated
Daily
Intake
(
EDI)
For
a
Child
=
0.0049
µ
g
of
DMH/
gm
food
x
1500
gm
food
=
7.4
µ
g
DMH/
person/
day
­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­
viii
1d.
Estimated
Daily
Intake
(
EDI)
of
Formaldehyde
for
an
Adult
=
0.00114
µ
g
of
Formaldehyde/
gm
food
x
3000
gm
food
=
3.42
µ
g
formaldehyde/
p/
d­­­­­­­
ix
1e.
Estimated
Daily
Intake
(
EDI)
of
Formaldehyde
for
an
child
=
0.00114
µ
g
of
formaldehyde/
gm
food
x
1500
gm
food
=
1.71
µ
g
formaldehyde/
p/
d
­­­­­­
x
II.
Data
Input
Parameters
for
Hydantoins
Used
as
a
(
Clay)
Preservative
in
Paper
1.
Rate
of
Application:
Maximum
level
of
2.4
lbs
active/
ton
of
aqueous
mineral
slurry
(
=
1200
ppm
of
active)

2.
Clay
Filler,
Active
filler
Concentration
=
1200
ppm
3.
1
g.
filler/
g
paper
pulp
4.
Standard
paper
weight:=
50
mg/
in2
5.
Mass
of
food
im
contact
with
surface
area
of
paper
treated
with
preservative
=
10
g
food/
in2
6.
Consumption
Factor
(
CF)
for
paper
treated
with
preservative
=
0.10
7.
Finished
preservative
Treated
Paper
=
8%
water
and
92%
pulp
(
Bob
Quick)
8
8.
Daily
Average
Food
Intake
(
adult)
=
3
kg
9.
Daily
Average
Food
Intake
(
child)
=
1500
g.
Page
9
of
18
Page
10
of
18
Output:

Calculations:

2a.
Concentration
of
DMH
In
Paper/
Pulp:

Rate
of
Appl.
x
10%
filler
x
MW
of
DMH/
MW
of
bismethylhydroxy
=
1200
ppm
x
0.1
x
128
MW
of
DMH/
188
MW
bismethylhydroxy
=
82
ppm
of
DMH
­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­
i
If
the
pulp
is
5%
in
the
slurry
water,
Amount
of
DMH
is:
0.05
x
82
ppm
=
4.1
ppm
of
DMH
in
slurry
water
­­­­­­­­­­­­­­­­
ii
If
mass
of
water
to
mass
of
pulp
is
2:
1
(
67%/
33%),
Amount
of
DMH/
g
of
pulp
is:
4.1
ppm
=
4.1
µ
g
DMH
x
2
=
8.2
µ
g
DMH/
g
pulp
­­­­­­­­­­­­­­­­­­­­­­­­­
iii
2b.
Concentration
of
DMH
In
Food:

Mass
of
DMH/
g
paper
x
mass
of
pulp/
g
paper
x
standard
mass
of
paper/
in2
paper/
mass
of
food/
in2
paper;
using
the
input
parameters
from
above:

8.2
µ
g
DMH/
g
paper
x0.92
g
pulp/
g
paper
x
0.05
g
paper/
in2
paper
x
10
g
food/
in2
paper
=
0.038
µ
g
DMH/
g
food
=
0.038
ppm
DMH­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­
iv
Taking
into
account
the
consumption
factor
(
CF)
of
0.10
for
treated
and
untreated
paper,
Amount
of
DMH
in
the
food
is:
=
0.1
x
0.038
ppm
=
0.0038
ppm
=
3.8
ppb
DMH
in
the
food/
diet­­­­­­­­­­­­­­­­­­­­
v
2c.
Concentration
of
Formaldehyde
in
Food:

If
the
methylhydroxy
and
or
bismethylhydroxy
convert
to
DMH,
then
the
amount
of
formaldehyde
produced
from
these
two
moities
is:

=
3.8
ppb
DMH
x
MW
formaldehyde/
MW
DMH
=
3.8
ppb
DMH
x
30/
128
=
0.89
ppb
­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­
vi
2d.
Estimated
Daily
Intake
(
EDI)
of
DMH
for
an
Adult
=
0.0038
µ
g
of
DMH/
gm
food
x
3000
gm
food
=
11.4
µ
g
food/
p/
d
­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­
vii
2e.
Estimated
Daily
Intake
(
EDI)
of
DMH
for
a
child
=
0.0038
µ
g
of
DMH/
gm
food
x
1500
gm
food
=
5.7
µ
g
food/
p/
d
­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­
viii
Page
11
of
18
2f.
Estimated
Daily
Intake
(
EDI)
of
Formaldehyde
for
an
Adult
=
0.00089
µ
g
of
formaldehyde/
gm
food
x
3000
gm
food
=
2.67
µ
g/
p/
d
­­­­­­­­­­­­­­­­­­­­­­­
ix
2g.
Estimated
Daily
Intake
(
EDI)
of
Formaldehyde
for
a
child
=
0.00089
µ
g
of
formaldehyde/
gm
food
x
1500
gm
food
=
1.34
µ
g/
p/
d
­­­­­­­­­­­­­­­­­­­­­­­­
x
III.
Input
Parameters
for
Hydantoins
Used
as
a
Coating
Preservative
1.
Rate
of
Application:
Maximum
level
of
2.4
lbs/
US
ton
of
aqueous
mineral
slurry
2.
Coating
Concentration
=
1200
ppm
3.
Slurry:
50%
by
weight
of
paper
coating
4.
Standard
paper
Weight:
50
mg/
in2
5.
Paper
coating
by
weight
of
paper:
10%

6.
Mass
of
food
in
contact
with
surface
area
of
paper
treated
with
the
coating:
10
g
food/
in2
7.
Consumption
Factor(
CF)
for
paper
treated
with
coating:
0.2*

8.
Daily
Average
Food
Intake
(
adult)
=
3000g
9.
Daily
Average
Food
Intake
(
child)
=
1500
g
Output:

IIIa.
Concentration
of
methylolhydantoin
coating
in
paper/
pulp
Calculations:

(
Application
Rate)
x
(
Coating
slurry
%
by
wt.
Of
paper
coating)
x
(
paper
coating
%
by
wt.
Of
paper)
x
(
standard
paper
wt.)
X
(
conversion
factor)

=
(
1200
µ
g
methylolhydantoins/
gm
coating
slurry)
x
(
0.50)(
0.10)(
50
mg/
in2)(
1
x10­
6
g/
µ
g)

=
3
x
10­
3
mg
methyloldhydantoin/
in2
of
paper­­­­­­­­­­­­­­­­­­­­­­­­
i
Page
12
of
18
IIIb.
Concentration
of
methylolhydantoin
in
food
(
Wt.
of
methoxyhydantoin/
paper
area)
x(
food
area
/
surface
area)
x(%
food
to
coated
paper)

=
(
3
x10­
3
methylolhydantoin/
in2
of
paper)
x
(
in2/
10
gm
food)(
0.2)
=
0.06
µ
g
methoxymethylhydantoin
=
0.06
ppm
=
60
ppb­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­
ii
DMH,
when
produced
asa
degradation
product
of
this
reaction
mixture
accounts
for
70.6%
and
from
the
degradation
of
the
two
hydroxymethyl
isomers,
formaldehyde
accounts
for
29.4%.
Hence
DMH
concentration
=
60
ppb
x
70.6/
100
=
42.4
ppb
­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­
iii
And
Formaldehyde
Concentration
=
60­
42.4=
17.6
ppb
­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­
iv
IIIc.
Concentration
of
DMH
in
Food:
(
Conc
of
Methylolhydantoin)
x
(%
DMH)

42.4
ppb­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­
v
IIId.
Concentration
of
formaldehyde
in
food
(
Concentration
of
methylolhydantoin)
x
(
percent
of
formaldehyde
produced)

=
60
ppb
x
0.294
=
17.6
ppb
­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­
iii
IIIe.
Estimated
Daily
Intake
(
EDI)
of
Methylolhydantoin
(
adult)
=
3000
g
food
/
p/
day
x
0.06
µ
g
hydroxymethylhydanotin/
gm
food
=
180
µ
g/
p/
d
 
iv
IIIe.
Estimated
Daily
Intake
(
EDI)
of
methylolhydanotin
(
child)
=
1500
g
food/
person/
day
x
0.06
µ
g
methylolhydantoin/
gm
food
=
90
µ
g/
p/
d­­­­­­­­­
v
IIIf.
Estimated
Daily
Intake
(
EDI)
of
DMH
for
an
adult
=
0.042
µ
g/
gm
food
x
3000
gm
food/
p/
d
=
126
µ
g/
p/
d
­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­
vi
IIIg.
Estimated
Daily
Intake
(
EDI)
of
DMH
for
a
child
=
0.042
µ
g/
gm
food
x
1500
gm
food/
p/
d
=
63
µ
g/
p/
d
­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­
vii
IIIh.
Estimated
Daily
Intake
of
Formadehyde
(
adult)
=
3000
g
food
x
17.6
ppb
=
53
µ
g/
p/
d
­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­
viii
IIIi
Estimated
Daily
Intake
of
formaldehyde
(
child)
=
1500
g
food
x
17.6
ppb
=
26.5
µ
g/
p/
d
­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­
ix
Page
13
of
18
A.
.
Aggregate
Concentrations
of
DMH
/
g
food
Three
use:

0.0049
µ
g
+
0.0038
µ
g
+
0.042
µ
g
=
0.051
µ
g­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­
x
A1.
Aggregated
Estimated
Daily
Intake
of
DMH
for
All
three
Uses
(
For
an
Adult):

=
3000
g
food
x
0.051
µ
g
DMH
=
153
µ
g/
day
­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­
xi
A2.
Aggregated
Estimated
Daily
Intake
of
DMH
for
a
Child:

1500
g
food
x
0.051
µ
g
DMH
=
76.5
µ
g/
day
­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­
xii
A3.
Aggregated
Estimated
Daily
Intake
of
Formaldehyde
from
All
three
Uses
(
adult):
(
3.42
+
2.67
+
53.0)
µ
g
=
59.09
µ
g
­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­
xiii
A4.
Estimated
Daily
Intake
of
Formaldehyde
for
All
Three
Uses
(
for
a
child):

(
1.71
+
1.34
+
26.50)
µ
g
=
29.55
µ
g
­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­
xiv
Table
1A
Dietary
Exposure
From
Hydantoins
Aggregate
EDI:
From
DMH
Aggregate
Exposure:
From
DMH
Male
Adult
=
153
µ
g/
d
153
µ
g/
70kg/
d
=
2.18
µ
g/
kg/
bw/
d
Female
Adult
=
153
µ
g/
d
153
µ
g/
60
kg/
d
=
2.55
µ
g/
kg/
bw/
d
Child
=
76.5
µ
g/
d
76.5
µ
g/
10kg/
d
=
7.6
µ
g/
kg/
bw/
d
Page
14
of
18
Table
1B
Dietary
Exposure
From
Formaldehyde
Released
From
Hydantoins
Aggregate
EDI
From
Formaldehyde
Aggregate
Exposure:
From
Formaldehyde
Male
Adult
=
59.09
µ
g/
d
59.09
µ
g/
70
kg/
d
=
0.844
µ
g/
kg/
bw/
d
Female
Adult
=
59.09
µ
g/
d
59.09
µ
g/
60kg/
d
=
0.98
µ
g/
kg/
d
Child
=
29.55
µ
g/
d
29.55
µ
g/
10
kg/
d
=
2.95
µ
g/
kg/
d
Provide
the
results
of
the
analyses
in
the
text
as
well
as
in
a
table
format.
Depending
on
the
complexity
of
the
analysis,
several
tables
may
be
needed.

As
stated
above,
for
acute
and
chronic
assessments,
AD
is
concerned
when
dietary
risk
exceeds
100%
of
the
PAD.
The
DEEM­
FCID
 
analyses
estimate
the
dietary
exposure
of
the
U.
S.
population
and
26
population
subgroups.
The
results
reported
in
Table(
s)
X
(
and
X)
are
for
the
general
U.
S.
Population,
all
infants
(<
1
year
old),
children
1­
2,
children
3­
5,
children
6­
12,
youth
13­
19,
females
13­
49,
adults
20­
49,
and
adults
50+
years.
Cancer
risk
is
determined
for
the
general
U.
S.
population
only.

Results
of
Acute
Dietary
Exposure
Analysis
Results
are
reported
at
the
[
95th/
99.9th]
percentile
of
exposure
because
the
assessment
incorporated
[
100%
CT
assumptions/
estimates
of
%
CT].
Page
15
of
18
Table
for
Tier
1
and
2
Analyses
(
i.
e.,
100%
CT
assumptions
were
made):

Table
X.
Results
of
Acute
Dietary
Exposure
Analysis
at
the
95th
Percentile
of
Exposure
Population
Subgroup
aPAD
(
mg/
kg/
day)
Exposure
(
mg/
kg/
day)
%
aPAD
General
U.
S.
Population
All
Infants
(<
1
year
old)

Children
1­
2
years
old
Children
3­
5
years
old
Children
6­
12
years
old
Youth
13­
19
years
old
Adults
20­
49
years
old
Females
13­
49
years
old
Adults
50+
years
old
Table
for
Tier
2a,
3,
and
4
Analyses
(
i.
e.,
estimates
of
%
CT
were
used):

Table
X.
Results
of
Acute
Dietary
Exposure
Analysis
Population
Subgroup
aPAD
(
mg/
kg/
day)
95th
Percentile
99th
Percentile
99.9th
Percentile
Exposure
(
mg/
kg/
day)
%
aPAD
Exposure
(
mg/
kg/
day)
%
aPAD
Exposure
(
mg/
kg/
day)
%
aPAD
General
U.
S.
Population
All
Infants
(<
1
year
old)

Children
1­
2
years
old
Children
3­
5
years
old
Children
6­
12
years
old
Youth
13­
19
years
old
Adults
20­
49
years
old
Females
13­
49
years
old
Adults
50+
years
old
Comments:
(
If
any
of
the
acute
dietary
risk
estimates
reported
in
the
table
exceed
HED's
level
of
concern,
include
a
commodity
contribution
analysis
and
summarize
in
general
terms).
Page
16
of
18
Results
of
Chronic
Dietary
Exposure
Analysis
Table
X.
Results
of
Chronic
Dietary
Exposure
Analysis
Population
Subgroup
cPAD
(
mg/
kg/
day)
Exposure
(
mg/
kg/
day)
%
cPAD
General
U.
S.
Population
All
Infants
(<
1
year
old)

Children
1­
2
years
old
Children
3­
5
years
old
Children
6­
12
years
old
Youth
13­
19
years
old
Adults
20­
49
years
old
Females
13­
49
years
old
Adults
50+
years
old
Comments:
(
If
any
of
the
chronic
dietary
risk
estimates
reported
in
the
table
exceed
HED's
level
of
concern,
include
a
commodity
contribution
analysis
and
summarize
in
general
terms).

Results
of
Cancer
Dietary
Exposure
Analysis
(
In
the
event
that
the
chemical
has
a
Q*,
the
following
language
can
be
used):

The
estimated
exposure
of
the
general
U.
S.
population
to
[
chemical
name]
is
[?]
mg/
kg/
day.
Applying
the
Q
1*
of
x.
xxx
(
mg/
kg/
day)­
1
to
the
exposure
value
results
in
a
cancer
risk
estimate
of
Y.
Y
x
10­
x.
Therefore,
estimated
cancer
risk
is
(
below/
above)
HED's
level
of
concern.

Table
X.
Results
of
Cancer
Dietary
Exposure
Analysis
Population
Subgroup
Exposure
(
mg/
kg/
day)
Estimated
Cancer
Risk
General
U.
S.
Population
Comments:
(
If
the
cancer
dietary
risk
exceeds
AD's
level
of
concern,
include
a
commodity
contribution
analysis
and
summarize
in
general
terms).

In
the
following
sections,
discussion
should
be
included
if
it
is
applicable
to
the
particular
chemical
under
discussion
and
if
some
parts
of
the
section
are
not
applicable
these
should
be
deleted.
Page
17
of
18
VI.
Discussion
of
Uncertainties
In
the
course
of
conducting
a
Tier
3/
4
dietary
exposure
analysis,
decisions
are
made
regarding
the
following:
the
residue
data
used
in
the
analysis
(
e.
g.,
field
trials,
monitoring
data,
etc.),
refinements
incorporated
in
DEEM­
FCID
 
such
as
percent
crop
treated
and
processing
factors,
sensitivity
analyses,
and
a
variety
of
other
issues
which
may
be
chemical­
or
crop­
specific.
Include
a
discussion
of
uncertainties
for
any
Tier
3/
4
dietary
exposure
analyses.
Only
relevant
topics
need
to
be
addressed.

Potential
Issues/
Topics
to
Include
in
the
"
Uncertainties"
Discussion

Sensitivity
analyses
­

Is
the
analysis
sensitive
to
the
assumption
of
½
LOD
values?
Are
there
certain
crops
that
are
not
expected
to
have
residues
(
or
have
very
low
%
CT);
and
therefore,
are
unlikely
to
contribute
to
the
risk?
What
types
of
sensitivity
analyses
were
conducted
and
what
did
the
results
show?


What
additional
data
could
be
used
to
refine
AD's
risk
estimates?

VII.
Conclusions
Provide
a
concise
summary
of
the
results
of
the
dietary
analyses
and
whether
or
not
risk
estimates
are
below
AD's
level
of
concern.
(
If
practical,
cut
and
paste
the
conclusions
from
the
Executive
Summary.)
The
following
language
may
also
be
used.
The
summary
table
below
should
be
included.
This
table
can
also
be
found
in
the
Format
and
Risk
Characterization
Guidance
(
SOP
00.2).

The
[
Tier
½
/
3/
4/
Monte
Carlo][
acute,
chronic,
cancer]
dietary
risk
assessment(
s)
were
conducted
for
all
supported
[
chemical
name]
food
uses.
For
all
supported
registered
commodities,
the
[
acute]
risk
estimates
are
[
above/
below]
the
Agency's
level
of
concern
at
the
[
95th/
99.9th]
exposure
percentile
for
the
general
U.
S.
population
(?%
of
the
[
a]
PAD)
and
[
all
population
subgroups/
most
highly
exposed
population
subgroup].
The
[
acute]
dietary
exposure
estimate
for
[
highest
exposed
population
subgroup]
is
[?%]
of
the
[
a]
PAD.
For
all
commodities,
the
[
chronic]
risk
estimates
are
[
above/
below]
the
Agency's
level
of
concern
for
the
general
U.
S.
population
(?%
of
the
[
c]
PAD)
and
[
all
population
subgroups/
most
highly
exposed
population
subgroup].
The
[
chronic]
dietary
exposure
estimate
for
[
highest
exposed
population
subgroup]
is
[?%]
of
the
cPAD.
The
cancer
risk
estimate
associated
with
exposure
to
[
chemical]
is
[?]
for
the
general
U.
S.
population,
and
is
[
above/
below]
the
Agency's
level
of
concern.
Page
18
of
18
Table
X.
Summary
of
Dietary
Exposure
and
Risk
for
[
Chemical]

Population
Subgroup**
Acute
Dietary
Chronic
Dietary
Cancer
Dietary
Exposure
(
mg/
kg/
day)
%
aPAD
Dietary
Exposure
(
mg/
kg/
day)
%
cPAD
Risk
General
U.
S.
Population
All
Infants
(<
1
year
old)

N/
A
Children
1­
2
years
old
Children
3­
5
years
old
Children
6­
12
years
old
Youth
13­
19
years
old
Adults
20­
49
years
old
Females
13­
49
years
old
Adults
50+
years
old
**
The
values
for
the
highest
exposed
population
for
each
type
of
risk
assessment
should
be
bolded.

VIII.
List
of
Attachments
Attach
acute
and
chronic
analyses,
including
commodity
files,
RDFs,
summary
pages
from
acute
and
chronic
analyses,
and
%
CT
memo
from
BEAD.
For
cancer
analyses,
delete
from
the
attachment
all
results
except
those
for
the
general
U.
S.
population.
Attachments
generated
by
the
DEEM­
FCID
 
model
should
be
formatted
in
either
Courier
TT8
or
Courier
New
font
(
size
8).
