Document ID: EPA-HQ-OPP-2003-0268-0002
Agency: epa
Document Type: Supporting & Related Material
Title: 
Posted Date: 2003-07-30T04:00Z

United
States
Prevention,
Pesticides
EPA
738­
R­
03­
002
Environmental
Protection
and
Toxic
Substances
May
29,
2003
Agency
(
7508C)

Reregistration
Eligibility
Decision
(
RED)

Dinocap
Reregistration
Eligibility
Decision
for
Dinocap
List
B
Case
2200
3
May
29,
2003
This
document
explains
the
U.
S.
Environmental
Protection
Agency's
(
hereafter
referred
to
as
EPA
or
"
the
Agency")
reregistration
eligibility
decision
(
RED)
for
dinocap
which
consists
of
a
voluntary
cancellation
of
all
products
registered
in
the
U.
S.
Because
the
registrant,
Dow
AgroSciences,
LLC
(
DAS)
has
expressed
interest
in
retaining
existing
tolerances
for
apples
and
grapes
for
import
purposes,
this
document
presents
only
a
dietary
risk
assessment
for
those
uses
and
specifically
addresses
the
data
requirements
for
support
of
the
import
tolerances.
The
following
RED
document
provides
background
information
on
the
pesticide
registration,
reregistration
and
tolerance
reassessment,
an
overview
of
the
uses
and
health
effects
associated
with
dinocap
and
a
summary
of
what
data
are
required
to
support
the
tolerances
on
apples
and
grapes
imported
into
the
U.
S.,
in
the
absence
of
a
U.
S.
registration.

I.
Introduction
In
1988,
the
Federal
Insecticide,
Fungicide
and
Rodenticide
Act
(
FIFRA)
was
amended
to
accelerate
the
reregistration
of
products
with
active
ingredients
registered
prior
to
November
1,
1984.
The
amended
Act
provides
a
schedule
for
the
reregistration
process.
There
are
five
phases
to
the
reregistration
process.
The
first
four
phases
of
the
process
focus
on
identification
of
data
requirements
to
support
the
reregistration
of
an
active
ingredient
and
the
generation
and
submission
of
data
to
fulfill
the
requirements.
The
fifth
phase
is
a
review
by
the
of
all
data
submitted
to
support
reregistration.

FIFRA
requires
the
Agency
to
determine
whether
pesticides
containing
an
active
ingredient
are
eligible
for
reregistration
before
calling
in
data
on
products
and
either
reregistering
products
or
taking
other
appropriate
regulatory
action.
Thus,
reregistration
involves
a
thorough
review
of
the
scientific
data
base
underlying
a
pesticide's
registration.
The
purpose
of
the
Agency's
review
is
to
reassess
the
potential
hazards
arising
from
the
currently
registered
uses
of
the
pesticide;
to
determine
the
need
for
additional
data
on
health
and
environmental
effects;
and
to
determine
whether
or
not
the
pesticide
meets
the
"
no
unreasonable
adverse
effects"
criteria
of
FIFRA.

On
August
3,
1996,
the
Food
Quality
Protection
Act
of
1996
(
FQPA)
was
signed
into
law.
This
Act
amends
FIFRA
to
require
that
by
2006
EPA
must
review
all
tolerances
in
effect
at
the
time
of
enactment.
FQPA
also
amends
the
Federal
Food,
Drug
and
Cosmetic
Act
(
FFDCA)
to
require
a
safety
finding
in
tolerance
reassessment
based
on
factors
including
an
assessment
of
cumulative
effects
of
chemicals
with
a
common
mechanism
of
toxicity.
At
this
time,
the
Agency
does
not
have
sufficient
reliable
information
concerning
common
mechanism
to
determine
whether
or
not
dinocap
shares
a
common
mechanism
of
toxicity
with
other
chemicals.
Therefore,
for
the
purpose
of
this
risk
assessment,
the
Agency
has
assumed
that
dinocap
does
not
share
a
common
mechanism
with
any
other
chemical.
4
II.
Regulatory
Background
Dinocap
was
the
subject
of
a
Special
Review
because
of
Agency
concerns
about
developmental
toxicity.
The
Position
Document
(
PD)
1
was
published
on
January
9,
1985
(
50
FR
1119)
and
the
PD
2/
3
on
October
29,
1986
(
51
FR
39577).
Special
Review
was
concluded
with
the
publication
of
the
PD
4
on
February
6,
1989
(
54
FR
5908).
In
the
PD
4,
the
Agency
required
that
all
dinocap
labels
be
revised
to
include
appropriate
health
hazard
statements
and
to
require
the
use
of
additional
protective
clothing
and
equipment
for
mixer/
loaders
and
applicators.

Dinocap,
a
List
B
chemical,
was
the
subject
of
a
Phase
4
Review
dated
January
30,
1991
and
a
Data­
Call­
In
Notice
(
DCI)
issued
on
September
10,
1991.
At
that
time,
the
current
registrant
Rohm
and
Haas
Company
(
R&
H)
had
indicated
that
they
intended
to
amend
registrations
to
drop
all
food/
feed
uses
for
end­
use
products
(
EPs).
In
the
Phase
4
Review,
data
were
required
under
residue
chemistry
guidelines
pending
submission
of
the
required
amendment
forms
and
revised
labels
for
all
EPs
confirming
that
food/
feed
uses
had
been
removed.
In
their
90­
day
response
to
the
Phase
4
DCI,
R&
H
requested
a
waiver
of
residue
chemistry
data
requirements
based
on
their
intention
to
delete
all
food/
feed
uses
from
their
product
labels.
The
registrant
subsequently
requested
that
the
Agency
retain
dinocap
tolerances
for
apples
and
grapes
as
import
tolerances.
Following
cancellation
by
R&
H
of
all
dinocap
food/
feed
uses
registered
in
the
U.
S.,
the
Agency
revoked
all
dinocap
tolerances,
except
those
for
apples
and
grapes
(
63
FR
206,
October
26,
1998).

The
registration
for
dinocap
was
transferred
from
R&
H
to
DAS
on
September
21,
2001.
On
February
12,
2002,
DAS
requested
voluntary
cancellation
pursuant
to
Section
6(
f)
of
FIFRA
of
their
U.
S.
product
registrations
for
dinocap
for
the
products
Karathane
WD
Ag
Fungicide
and
Miticide
(
EPA
Registration
No.
62719­
384),
Karathane
Liquid
Concentrate
Ag
Fungicide
and
Miticide
(
EPA
Registration
No.
62719­
385)
and
Karathane
Technical
Ag
Fungicide
and
Miticide
(
EPA
Registration
No.
62719­
390).
The
Agency
announced
its
receipt
of
the
above­
mentioned
cancellation
requests
in
the
Federal
Register
on
April
26,
2002
[
OPP­
2002­
0013;
FRL­
6833­
8].
The
Agency
did
not
receive
any
comments
specific
to
these
cancellations;
therefore,
the
cancellation
order
was
effective
on
October
24,
2002.
Because
dinocap
products
have
not
been
marketed
in
the
U.
S.
for
several
years,
existing
stocks
are
expected
to
be
negligible.

III.
Uses
Dinocap
is
a
foliar
fungicide/
miticide
used
to
control
powdery
mildew.
Dinocap
is
applied
to
apples
and
grapes
outside
of
the
U.
S.,
mainly
in
Europe,
the
Middle
East
and
northern
Africa.
There
are
currently
no
registered
dinocap
products
in
the
U.
S.
DAS,
the
registrant
of
dinocap,
intends
to
support
tolerances
for
dinocap
residues
in/
on
apples
and
grapes
to
permit
legal
importation
of
these
commodities
into
the
U.
S.

IV.
Health
Effects
The
doses
and
endpoints
for
dietary
risk
assessment
were
selected
by
the
Hazard
Identification
Assessment
Review
Committee
(
HIARC)
(
memo
dated
February
23,
2000).
The
5
HIARC
established
an
acute
toxicity
endpoint
for
females
of
reproductive
age
(
females
13+
years
old)
and
determined
that
a
risk
assessment
for
acute
dietary
exposure
is
not
necessary
for
the
general
population.
The
acute
endpoint
was
derived
from
a
mouse
developmental
study
(
MRID
41313001)
based
on
a
slight
(
nonsignificant)
increase
in
incidences
of
cleft
palate
and
eyelids­
open
relative
to
controls
that
occurred
in
the
absence
of
maternal
toxicity.
The
No
Observed
Adverse
Effect
Level
(
NOAEL)
was
4
mg/
kg/
day
and
the
Lowest
Observed
Adverse
Effect
Level
(
LOAEL)
was
10
mg/
kg/
day.

The
chronic
dietary
endpoint
was
selected
from
a
chronic
feeding
study
in
dogs
(
MRID
41065401,
Acc.
Nos.
247957
&
247959).
The
NOAEL
for
systemic
toxicity
was
0.375
mg/
kg/
day
and
the
LOAEL
was
1.5
mg/
kg/
day
based
on
effects
on
the
eye.

The
FQPA
committee
recommended
that
the
FQPA
safety
factor
for
the
protection
of
infants
and
children
be
retained
at
10x
for
all
population
subgroups
when
assessing
acute
and
chronic
exposure.
The
reasons
are:
(
1)
there
is
concern
for
the
quantitative
and
qualitative
increase
in
susceptibility
observed
in
fetuses
following
in
utero
exposure
in
the
prenatal
developmental
studies
in
mice
and
rabbits;
and
(
2)
there
is
a
data
gap
for
the
developmental
neurotoxicity
study
in
the
rat.

The
acute
reference
dose
(
aRfD)
is
0.04
mg/
kg/
day
and
the
acute
population
adjusted
dose
(
aPAD)
is
0.004
mg/
kg/
day.
The
chronic
reference
dose
(
cRfD)
is
0.0038
mg/
kg/
day
and
the
chronic
population
adjusted
dose
(
cPAD)
is
0.00038
mg/
kg/
day.
The
population
adjusted
dose
is
the
reference
dose
divided
by
the
FQPA
safety
factor.

The
Agency
has
classified
dinocap
as
a
Group
E
"
not
likely"
carcinogen.
It
was
negative
for
inducing
mutations
in
all
studies
of
the
standard
mutagenicity
battery
except
the
Ames
test.
In
Ames
studies,
dinocap
was
weakly
positive
at
best
and
only
at
high
doses.

For
more
detailed
information
on
the
potential
health
effects
associated
with
dinocap,
please
refer
to
the
"
Dinocap
Toxicology
Chapter
for
the
RED,"
dated
April
18,
2000,
which
is
available
on
the
Agency's
web
page
at
http://
www.
cfpub.
epa.
gov/
oppref/
rereg/
status.
cfm?
show=
rereg
and
in
the
Public
Docket.

V.
Dietary
Risk
Assessment
Acute
and
chronic
dietary
exposure
assessments
were
conducted
to
determine
the
dietary
exposure
estimates
associated
with
the
use
of
dinocap
in/
on
apples
and
grapes
to
support
the
RED.
The
qualitative
nature
of
the
residue
in
plants
and
animals
are
not
adequately
understood
and
no
acceptable
magnitude
of
the
residue
or
processing
data
in/
on
imported
apples
or
grapes
are
currently
available.
Therefore,
the
dietary
risk
assessment
was
conducted
two
ways,
using
the
current
tolerances
of
0.1
ppm
and
using
Maximum
Residue
Limits
(
MRLs)
recommended
by
the
Joint
FAO/
WHO
Meeting
on
Pesticide
Residues
(
JMPR).
There
are
European
data
which
have
been
reviewed
by
the
JMPR.
The
JMPR
proposes
MRLs
for
individual
pesticides
in
different
food
and
feed
items,
and
provides
advice
on
the
acceptable
levels
of
pesticide
residues
in
food
moving
in
international
trade.
Residues
of
dinocap
in
the
European
trials
were
<
0.05
(
ND)
to
0.09
ppm
in
6
apples
and
<
0.05
to
0.67
ppm
in
grapes.
In
1988,
JMPR
recommended
MRLs
of
0.2
for
apples
and
1
ppm
for
grapes.

No
processing
data
are
available;
therefore,
default
processing
factors
were
used.
Information
is
available
to
estimate
the
percent
of
the
import
apple
and
grape
crops
that
are
treated
with
dinocap.
Less
than
5%
of
the
apples
and
grapes
consumed
in
the
U.
S.
are
imported
and
less
than
1%
of
those
are
treated
with
dinocap.
Thus,
the
calculated
percent
crop
treated
(%
CT)
for
dinocap
is
0.05%
which
has
been
rounded
up
to
0.1%
in
the
chronic
dietary
risk
assessment.

Dinocap
acute
and
chronic
dietary
exposure
assessments
were
conducted
using
the
Dietary
Exposure
Evaluation
Model
(
DEEMTM)
software
Version
7.73,
which
incorporates
consumption
data
from
USDA's
Continuing
Survey
of
Food
Intake
by
Individuals
(
CSFII),
1989­
1992.
The
1989­
1992
data
are
based
on
the
reported
consumption
of
more
than
10,000
individuals
over
3
consecutive
days
and
therefore
represent
more
than
30,000
unique
"
person
days"
of
data.

Irrespective
of
the
residue
data
used
(
i.
e.,
current
U.
S.
tolerances
or
MRLs),
acute
and
chronic
dietary
risk
estimates
are
well
below
the
Agency's
level
of
concern
for
all
supported
dinocap
food
uses.
Acute
dietary
risk
is
<
1%
of
the
aPAD
for
the
only
subpopulation
of
concern,
females,
13­
50
years
old.
Chronic
dietary
risk
is
<
1%
of
the
cPAD
for
the
U.
S.
general
population
and
all
subpopulations.

For
more
detailed
information
on
the
dietary
risk
assessment
for
dinocap,
please
refer
to
the
"
Dinocap
Acute
and
Chronic
Dietary
Exposure
Assessment,"
dated
November
7,
2001,
which
is
available
on
the
Agency's
web
page
at
http://
www.
cfpub.
epa.
gov/
oppref/
rereg/
status.
cfm?
show=
rereg
and
in
the
Public
Docket.

VI.
Tolerance
Reassessment
Summary
There
are
currently
no
registered
food/
feed
uses
of
dinocap
in
the
U.
S.
The
established
dinocap
tolerances
for
food
and
feed
commodities
have
been
revoked
except
those
for
apples
and
grapes.
DAS,
the
basic
producer,
intends
to
support
tolerances
for
dinocap
residues
in/
on
apples
and
grapes
to
permit
legal
importation
of
these
commodities
into
the
U.
S.,
in
the
absence
of
a
U.
S.
registration.

Tolerances
for
dinocap
are
currently
expressed
in
terms
of
combined
negligible
residues
of
a
fungicide
and
insecticide
that
is
a
mixture
of
2,4­
dinitro­
6­
octylphenyl
crotonate
and
2,6­
dinitro­
4­
octylphenyl
crotonate
in/
on
apples
and
grapes
at
0.1
ppm
[
40
CFR
§
180.341(
a)].
Current
U.
S.
tolerances
are
0.1
ppm
(
negligible)
on
both
crops
[
40
CFR
§
180.341].

There
are
currently
no
Codex
MRLs
established
for
residues
of
dinocap.
However,
in
1988,
JMPR
recommended
dinocap
MRLs
of
0.2
for
apples
and
1
ppm
for
grapes.
Harmonization
of
the
tolerance
expression/
definition
and
tolerances
between
Codex
MRLs
and
U.
S.
tolerances
cannot
be
achieved
until
the
outstanding
metabolism
and
residue
data
have
been
submitted.
1
(
N)
=
negligible
residues;
however,
the
Agency
is
removing
the
"(
N)"
designation
from
all
entries
to
conform
to
current
Agency
administrative
practice.

2
These
commodities
were
included
in
the
dietary
risk
assessment
for
dinocap
using
the
Current
Tolerance
level.
Additional
confirmatory
field
trial
residue
data
are
required;
therefore,
the
final
tolerance
may
be
revised.

7
Table
1.
Tolerance
Reassessment
Summary
for
Dinocap.

Commodity
Current
Tolerance
(
ppm)
Reassessed
Tolerance
(
ppm)
Comments
[
Corrected
Commodity
Definition]

Tolerances
Established
Under
40
CFR
§
180.341(
a)

Apples
0.1(
N)
1
To
be
determined2
[
Apple]

Grapes
0.1(
N)
To
be
determined
[
Grape]

VII.
Data
Gaps
The
toxicology
database
for
dinocap
is
considered
adequate
for
the
current
risk
assessment.
Acute,
subchronic
and
a
developmental
neurotoxicity
study
in
rats
are
required
based
on
concerns
for
the
severe
effects
(
malformations)
seen
in
the
developmental
toxicity
studies
in
mice
and
rabbits,
as
well
as
for
the
neurological
effects
demonstrated
in
mice
and
dogs.

There
are
several
data
gaps
for
residue
chemistry.
Data
are
required
to
describe
the
qualitative
nature
of
dinocap
residues
in
plants
and
animals.
Magnitude
of
the
residue
in/
on
imported
apples
and
grapes
must
be
addressed
with
field
residue
data
reflecting
the
maximum
use
patterns
for
the
representative
formulations
in
the
areas/
countries
where
dinocap
will
be
sold
and
used.
DAS
may
not
need
to
conduct
all
new
studies
to
fulfill
these
requirements,
but
may
be
able
to
rely
on
existing
studies
developed
for
a
foreign
registration
or
Codex
MRLs
to
support
the
proposed
tolerance.

Table
2
below
lists
the
confirmatory
data
requirements
for
supporting
the
apple
and
grape
tolerances
for
import
purposes.
These
requirements
are
consistent
with
EPA's
"
Guidance
on
Pesticide
Import
Tolerances
and
Residue
Data
for
Imported
Food,"
65
FR
106;
35069­
350­
90,
June
1,
2000.

Table
2.
Data
Requirements
for
Dinocap
Import
Tolerances.

Data
Requirements
New
OPPTS
Guideline
Number
Old
Guideline
Number
TOXICOLOGY
Acute
Neurotoxicity
Screening
Battery,
Rat
870.6200
81­
8
Subchronic
Neurotoxicity
Study,
Rat
82­
7
Developmental
Neurotoxicity
Study,
Rat
870.6300
83­
6
RESIDUE
CHEMISTRY
Directions
for
Use
860.1200
171­
3
Data
Requirements
New
OPPTS
Guideline
Number
Old
Guideline
Number
8
Nature
of
the
Residue,
Plants
870.1300
171­
4A
Nature
of
the
Residue,
Livestock
171­
4B
Storage
Stability,
Plants
860.1380
171­
4E
Crop
Field
Trials
(
Apple
&
Grapes)
860.1500
171­
4K
Processed
Food
(
Apple
&
Grapes)
860.1520
171­
4L
A
ruminant
metabolism
study
is
included
in
the
above
list
because
wet
apple
pomace
is
a
livestock
feed
item.
In
order
to
waive
this
study,
registrants
must
convincingly
document
that
it
is
unlikely
that
imported
apples
or
wet
pomace
would
be
significant
feed
items
in
the
U.
S.
or
exporting
countries
and/
or
that
there
are
not
significant
imports
of
livestock
commodities.

Before
conducting
any
toxicology
or
residue
chemistry
study,
the
registrant
should
submit
study
protocols
for
EPA
comment
if
they
have
any
questions
regarding
study
design
and
conduct.
The
Agency
will
attempt
to
harmonize
with
international
standards
to
the
extent
possible.

VIII.
Regulatory
Conclusion
The
Agency
has
completed
its
reregistration
eligibility
decision
for
the
fungicide/
miticide,
dinocap,
which
consists
of
a
voluntary
cancellation
of
all
U.
S.
product
registrations.
Because
the
registrant
has
indicated
their
intention
to
retain
the
existing
tolerances
for
apples
and
grapes
for
import
purposes,
EPA
has
conducted
a
dietary
risk
assessment
for
dinocap.
Although
there
are
data
gaps,
the
Agency
has
used
protective
assumptions
including
a
10x
safety
factor
and
tolerance
level
residue
values
to
determine
that
dietary
risk
is
minimal,
less
than
1%
of
the
acute
and
chronic
PADs
for
all
population
subgroups.
EPA
finds
that
there
is
a
reasonable
certainty
that
no
harm
will
result
from
dinocap
use
on
apples
and
grapes
imported
into
the
U.
S.
Confirmatory
data
are
required
as
outlined
in
the
previous
section.

/
s
/
____________________________________
Lois
A.
Rossi,
Director
Special
Review
and
Reregistration
Division