Document ID: EPA-HQ-OPP-2005-0505-0003
Agency: epa
Document Type: Supporting & Related Material
Title: 
Posted Date: 2006-02-22T05:00Z

United
States
Prevention,
Pesticides
EPA
738­
R­
06­
001
Environmental
Protection
and
Toxic
Substances
January
2006
Agency
(
7508C)
__________________________________________________________________________

Report
of
the
Food
Quality
Protection
Act
(
FQPA)
Tolerance
Reassessment
Progress
and
Risk
Management
Decision
(
TRED)
for
Tridemorph
Page
2
of
7
Report
of
the
Food
Quality
Protection
Act
(
FQPA)
Tolerance
Reassessment
Progress
and
Risk
Management
Decision
(
TRED)
for
Tridemorph
Approved
By:

_______________________________
Debra
Edwards,
Ph.
D.
Director,
Special
Review
and
Reregistration
Division
_______________________________
Date
Page
3
of
7
I.
Regulatory
Determination
The
Federal
Food,
Drug
and
Cosmetic
Act
(
FFDCA),
as
amended
by
FQPA,
requires
the
Environmental
Protection
Agency
(
the
Agency
or
EPA)
to
reassess
all
the
tolerances
for
registered
chemicals
in
effect
on
the
day
before
enactment
of
the
FQPA
on
August
3,
1996.
In
reassessing
these
tolerances,
the
Agency
must
consider,
among
other
things,
aggregate
risks
from
non­
occupational
sources
of
pesticide
exposure,
whether
there
is
increased
susceptibility
to
infants
and
children,
and
the
cumulative
effects
of
pesticides
with
a
common
mechanism
of
toxicity.
When
a
safety
finding
has
been
made
that
aggregate
risks
are
not
of
concern,
the
tolerances
are
considered
reassessed.
Existing
tolerances
associated
with
tridemorph
must
be
reassessed
in
accordance
with
FFDCA,
as
amended
by
FQPA.

Tridemorph
(
active
ingredient
number
121401)
is
a
systemic
fungicide
used
to
treat
black
and
yellow
sigatoka
on
banana
and
plantain
plants.
There
are
no
U.
S.
registrations
for
tridemorph
use,
and
as
such,
the
existing
tolerance
is
commonly
referred
to
as
an
import
tolerance.
Because
there
are
no
U.
S.
registrations,
there
are
no
expected
ecological,
drinking
water,
occupational
or
residential
exposures
in
the
U.
S.
Dietary
(
food)
residues
on
imported
bananas
and
plantains
are
expected
to
be
the
only
source
of
potential
exposure
to
tridemorph;
therefore,
only
a
dietary
(
food)
risk
assessment
was
conducted
for
this
TRED.

The
Agency
has
evaluated
the
human
health
risks
associated
with
tridemorph
residues
on
commodities
and
has
determined
that
there
is
a
reasonable
certainty
that
no
harm
will
result
from
exposure
to
these
residues.
In
making
this
determination,
EPA
has
considered
dietary
exposure
from
food
sources
of
pesticide
exposure
(
the
only
exposure
route)
for
which
there
is
reliable
information.
Therefore,
the
one
(
1)
tolerance
for
residues
of
tridemorph
on
banana
(
including
plantain)
is
now
considered
reassessed
as
safe
under
section
408(
q)
of
FFDCA,
as
amended
by
FQPA.

The
Agency's
human
health
safety
finding
for
the
pesticide
tridemorph
is
summarized
in
Tridemorph
HED
Risk
Assessment
for
Tolerance
Reassessment
Eligibility
Decision
(
TRED)
Document,
dated
November
7,
2005.
For
further
details,
please
refer
to
this
risk
assessment
and
other
technical
documents
pertaining
to
the
tridemorph
TRED,
which
are
available
on
the
internet
at
www.
regulations.
gov
under
Docket
#
EPA­
HQ­
OPP­
2005­
0505
and
in
the
public
docket
for
viewing.

The
Agency
is
issuing
this
TRED
document
for
tridemorph
as
announced
in
a
Notice
of
Availability
published
in
the
Federal
Register.
The
Agency
is
providing
a
30­
day
comment
period
for
stakeholders
to
respond
to
this
risk
management
decision.
If
substantive
information
is
received
during
the
comment
period
that
indicates
a
need
to
refine
any
of
EPA's
assumptions
or
a
need
for
risk
mitigation,
then
this
decision
will
be
modified
as
appropriate
through
an
amendment
to
the
TRED.
Page
4
of
7
II.
Tolerance
Reassessment
A.
FQPA
Assessment
Supporting
Tolerance
Reassessment
Decision
The
Agency
has
conducted
a
human
health
risk
assessment
to
ensure
that
the
tridemorph
tolerance
meets
the
new
safety
standards
established
by
FFDCA,
as
amended
by
FQPA.
This
risk
assessment
for
tridemorph
includes
evaluation
of
potential
susceptibility
to
infants
and
children
and
dietary
exposure
to
adults
and
children.
EPA
also
considered
potential
cumulative
risks
for
tridemorph
and
other
substances
sharing
a
common
mechanism
of
toxicity,
as
well
as
potential
endocrine
effects
associated
with
tridemorph.

EPA
has
determined
that
risk
from
exposure
to
tridemorph
is
within
its
own
"
risk
cup."
In
other
words,
EPA
is
able
to
conclude
today
that
the
tolerance
for
tridemorph
meets
the
FQPA
safety
standards.
Although
the
toxicological
database
had
some
deficiencies,
the
database
as
a
whole
is
adequate
for
tolerance
reassessment.
In
reaching
this
determination,
the
Agency
has
considered
the
available
information
on
the
potential
sensitivity
of
infants
and
children,
as
well
as
acute
and
chronic
food
exposure.
Because
there
are
no
existing
registrations
for
the
use
of
tridemorph
in
the
U.
S.,
only
acute
and
chronic
dietary
(
food)
assessments
were
conducted
for
potential
exposure
to
tridemorph
per
se
residues
in/
on
imported
bananas/
plantains.
Results
of
both
dietary
assessments
indicate
that
the
human
health
risks
from
these
exposures
are
considered
to
be
within
acceptable
levels;
that
is,
all
assessed
risks
from
exposure
to
tridemorph
"
fit"
within
the
individual
risk
cup
for
this
chemical.
The
Agency's
risk
assessment
conclusions
are
summarized
below.

FQPA
Safety
Factor
Considerations.
The
FFDCA,
as
amended
by
the
FQPA,
directs
the
Agency
to
use
an
additional
tenfold
(
10X)
safety
factor
to
take
into
account
potential
pre­
and
post­
natal
toxicity
and
completeness
of
the
database
with
respect
to
exposure
and
toxicity
to
infants
and
children.
FFDCA
authorizes
the
Agency
to
modify
the
10X
safety
factor
only
if
reliable
data
demonstrate
that
the
resulting
level
of
exposure
would
be
safe
for
infants
and
children.

The
available
developmental
toxicity
information
indicates
increased
quantitative
and
qualitative
susceptibility
(
increased
incidence
for
developmental
anomalies)
in
rats
and
increased
quantitative
susceptibility
(
reduction
in
fetal
weight)
in
mice
since
the
developmental
findings
occurred
in
the
absence
of
maternal
toxicity.

The
degree
of
concern
for
the
prenatal
susceptibility
effects
in
rabbits
and
post­
natal
susceptibility
effects
in
rats
could
not
be
determined
when
the
risk
assessment
was
completed
due
to
data
gaps
in
the
toxicological
database.
Thus,
during
the
preparation
of
this
TRED,
to
address
the
potential
degree
of
concern
for
infants
and
children,
an
FQPA
safety
factor
of
10X
was
retained
for
both
the
acute
and
chronic
reference
dose
derivations
to
account
for
uncertainty
due
to
these
data
gaps.
Although
a
series
of
toxicity
studies,
which
may
address
the
identified
data
gaps,
were
submitted
after
the
risk
assessment
was
completed,
the
Agency
has
not
conducted
a
complete
review
of
these
data.
However,
based
on
a
preliminary
review
of
the
data,
Page
5
of
7
the
Agency
is
confident
that
the
10X
FQPA
safety
factor
is
adequately
protective
of
potential
effects
to
infants
and
children.

Dietary
Risks
(
food).
Acute
and
chronic
dietary
(
food)
risk
assessments
were
conducted
using
the
Dietary
Exposure
Evaluation
Model
(
DEEM­
FCID
 
,
Version
2.03),
which
use
food
consumption
data
from
the
USDA's
Continuing
Surveys
of
Food
Intakes
by
Individuals
(
CSFII)
from
1994­
1996
and
1998.
In
these
analyses,
the
dietary
exposure
and
risk
estimates
resulting
from
food
intake
were
determined
for
the
general
U.
S.
population
and
various
population
subgroups.
The
acute
and
chronic
dietary
exposure
analyses
for
tridemorph
were
conducted
using
unrefined
Tier
1
dietary
exposure
assumptions
for
all
uses.
The
Tier
1
analysis
assumes
tolerance
level
residues,
100%
crop
treated
for
all
commodities,
and
DEEM­
FCID
 
default
processing
factors
for
the
processed
commodities.

Dietary
risk
to
each
population
group
is
measured
by
a
population
adjusted
dose
(
PAD),
which
is
the
reference
dose
(
RfD)
adjusted
for
the
FQPA
safety
factor.
RfD
is
defined
as
the
estimated
human
exposure
level
believed
to
have
no
adverse
impact
on
human
health.
For
tridemorph,
the
acute
RfD
is
the
No
Observed
Adverse
Effects
Level
(
NOAEL)
divided
by
1,000X
(
10X
for
interspecies
extrapolation,
10X
for
intraspecies
variation,
and
10X
FQPA
safety
factor
due
to
toxicity
data
gaps).
The
acute
RfD
for
tridemorph
is
based
on
developmental
effects
observed
in
the
rat
developmental
study.
An
acute
RfD
was
selected
for
the
subpopulation
females
13­
49
only.
An
acute
RfD
was
not
selected
for
the
U.
S.
general
population
or
other
population
subgroups,
because
no
effect
attributable
to
a
single
(
or
few)
day(
s)
oral
exposure
was
observed
in
available
animal
studies.

Since
no
acceptable
chronic
dietary
study
was
available
when
the
risk
assessment
was
completed,
the
chronic
RfD
is
based
on
the
NOAEL
established
by
a
subchronic
dietary
dog
study,
which
included
clinical
signs
such
as
change
in
body
weight
and
histopathology.
Since
the
endpoint
is
based
on
the
subchronic
study,
an
additional
3X
uncertainty
factor
(
UF)
was
applied
for
the
extrapolation
from
subchronic
to
chronic
study
effects.
The
chronic
population
adjusted
dose
(
cPAD)
for
tridemorph
is
the
RfD
divided
by
the
3,000X
(
10X
for
interspecies
extrapolation,
10X
for
intraspecies
variation,
10X
FQPA
safety
factor
due
to
toxicity
data
gaps,
and
3X
uncertainty
factor
for
the
extrapolation
of
subchronic
to
chronic
study
effects).
A
dietary
risk
estimate
that
is
less
than
100%
of
the
aPAD
or
cPAD
does
not
exceed
EPA's
level
of
concern.

The
Agency's
Tier
1
acute
and
chronic
dietary
risk
assessments
indicate
that
dietary
risk
from
tridemorph
residues
in
food
are
low
and
below
the
Agency's
level
of
concern.
At
the
95th
percentile,
the
acute
dietary
risk
estimate
for
the
population
subgroup
females
13­
49
years
is
9%
of
the
aPAD.
The
mean
chronic
dietary
exposure
estimate
for
the
highest
exposed
population
subgroup,
children
1­
2
years
of
age,
is
18%
of
the
cPAD.

Because
there
are
no
tridemorph
registrations
in
the
U.
S.,
drinking
water,
occupational,
and
residential
exposures
to
the
U.
S.
population
are
not
anticipated.
Therefore,
drinking
water,
occupational,
residential,
and
aggregate
risk
assessments
were
not
conducted.
Page
6
of
7
B.
Cumulative
Assessment
Unlike
other
pesticides
for
which
EPA
has
followed
a
cumulative
risk
approach
based
on
common
mechanism
of
toxicity,
EPA
has
not
made
a
common
mechanism
of
toxicity
finding
as
to
tridemorph
and
any
other
substances,
and
tridemorph
does
not
appear
to
produce
a
toxic
metabolite
produced
by
other
substances.
For
the
purposes
of
this
tolerance
reassessment
action,
therefore,
EPA
has
not
assumed
that
tridemorph
has
a
common
mechanism
of
toxicity
with
other
substances.
For
information
regarding
EPA's
efforts
to
determine
which
chemicals
have
a
common
mechanism
of
toxicity
and
to
evaluate
the
cumulative
effects
of
such
chemicals,
see
the
policy
statements
released
by
EPA's
Office
of
Pesticide
Programs
concerning
common
mechanisms
determinations
and
procedures
for
cumulating
effects
from
substances
found
to
have
a
common
mechanism
on
EPA's
website
at
http://
www.
epa.
gov/
pesticides/
cumulative/.

C.
Endocrine
Disruptor
Effects
EPA
is
required
under
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
recommendations
of
its
Endocrine
Disruptor
and
Testing
Advisory
Committee
(
EDSTAC),
EPA
determined
that
there
was
a
scientific
basis
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).

Based
on
the
available
information,
tridemorph
was
reported
to
cause
degeneration
of
the
testes
with
oligospermia
and
azoospermia
in
the
subchronic
rat
and
cryptorchidism
(
testes
failed
to
descend),
dysplasia
and
atrophy
of
the
testes
in
the
subchronic
dog
study.
However,
these
findings
are
preliminary
and
need
to
be
confirmed.
When
additional
appropriate
screening
and/
or
testing
protocols
being
considered
under
the
Agency's
EDSP
have
been
developed,
tridemorph
may
be
subjected
to
further
screening
and/
or
testing
to
better
characterize
effects
related
to
endocrine
disruption.

D.
Tolerance
Summary
Tolerances
Listed
in
40
CFR
§
180.372
A
tolerance
has
been
established
for
residues
of
tridemorph
in
or
on
imported
bananas
at
0.1
ppm,
which
includes
the
same
allowance
for
residues
in
or
on
plantains.
The
tolerance
for
residues
of
tridemorph
in/
on
plant
commodities
is
expressed
in
terms
of
residues
of
tridemorph
per
se
(
2,6­
dimethyl­
4­
tridecylmorpholine).
New
foreign
residue
data
indicates
the
established
tolerance
must
be
increased
to
1.0
ppm.
Since
there
are
no
U.
S.
registrations,
the
tolerance
should
be
footnoted
to
so
indicate.
Page
7
of
7
Table
1:
Tolerance
Summary
for
Tridemorph
(
40
CFR
§
180.372)

Commodity
Current
Tolerance
(
ppm)
Reassessed
Tolerance
(
ppm)
Comments
Bananas
0.1
ppm
1.0
ppm
The
tolerance
should
be
footnoted
to
indicate
that
there
are
no
U.
S.
registrations
associated
with
tridemorph.

There
are
no
Codex
maximum
residue
levels
(
MRLs)
for
tridemorph.
Therefore,
no
questions
of
compatibility
with
U.
S.
tolerances
exist.

III.
Data
Gaps
and
Confirmatory
Data
Requirements
The
Agency
concluded
that
the
database
for
tridemorph
is
adequate
for
tolerance
reassessment
purposes,
but
identified
some
data
gaps
during
the
preparation
of
the
risk
assessment.
To
account
for
the
uncertainty
associated
with
the
lack
of
these
data,
a
10X
FQPA
safety
factor
was
used
in
both
chronic
and
acute
dietary
assessments
to
account
for
the
absence
of
these
data,
and
an
additional
3X
UF
was
used
in
the
chronic
dietary
assessment
for
extrapolation
of
subchronic
to
chronic
effects.
Further,
highly
conservative
exposure
assumptions
were
used
in
the
unrefined
Tier
I
dietary
risk
assessment
(
i.
e.
100%
crop
treated,
default
processing
factors,
and
tolerance
level
residues).

Recently,
after
completion
of
the
risk
assessment,
the
registrant
submitted
a
series
of
toxicity
studies
(
acute
battery,
subchronic
oral
toxicity
in
rats,
chronic
oral
toxicity
in
rats,
mice
and
dogs,
developmental
toxicity
studies
and
a
two
generation
reproduction
study
in
rats,
and
a
battery
of
mutagenic
tests).
Although
these
studies
may
address
the
identified
data
gaps,
the
Agency
has
not
conducted
a
complete
review
of
these
data
at
this
time.
However,
based
on
a
preliminary
review,
the
Agency
is
confident
that
the
10X
FQPA
safety
factor,
which
was
retained
to
account
for
uncertainty
due
to
toxicity
data
gaps,
in
addition
to
the
3X
UF
applied
to
account
for
extrapolation
from
subchronic
to
chronic
effects
in
the
chronic
risk
assessment,
as
well
as
highly
conservative
exposure
assumptions,
are
adequately
protective
of
all
populations,
including
infants
and
children.
If,
following
a
complete
review
of
these
data,
information
indicates
that
additional
measures
are
necessary
to
ensure
that
the
tridemorph
tolerance
meets
the
required
safety
standards,
the
Agency
will
amend
this
TRED
accordingly.