Document ID: EPA-HQ-OPP-2005-0491-0002
Agency: epa
Document Type: Supporting & Related Material
Title: 
Posted Date: 2006-01-11T05:00Z

United
States
Prevention,
Pesticides
EPA
738­
R­
05­
015
Environmental
Protection
and
Toxic
Substances
November
2005
Agency
(
7508C)
__________________________________________________________________________

Report
of
the
Food
Quality
Protection
Act
(
FQPA)
Tolerance
Reassessment
Progress
and
Risk
Management
Decision
(
TRED)
for
Bitertanol
Page
2
of
7
Report
of
the
Food
Quality
Protection
Act
(
FQPA)
Tolerance
Reassessment
Progress
and
Risk
Management
Decision
(
TRED)
for
Bitertanol
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
the
Food
Quality
Protection
Act
(
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
bitertanol
must
be
reassessed
in
accordance
with
FFDCA,
as
amended
by
FQPA.

Bitertanol
(
active
ingredient
number
121601)
is
a
postemergence
fungicide
used
to
treat
black
sigatoka
leaf
spot
on
banana
and
plantain.
There
are
no
U.
S.
registrations
for
bitertanol
use;
however,
there
is
a
tolerance
for
imported
bananas/
plantains
treated
with
bitertanol.
Therefore,
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
bitertanol;
thus,
only
a
dietary
(
food)
risk
assessment
was
conducted
for
this
TRED.

The
Agency
has
evaluated
the
human
health
risks
associated
with
bitertanol
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
bitertanol
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
bitertanol
is
summarized
in
Bitertanol.
Revised
HED
Chapter
of
the
Tolerance
Reassessment
Eligibility
Decision
Document
(
TRED),
dated
November
30,
2005.
For
further
details,
please
refer
to
this
risk
assessment
and
other
technical
documents
pertaining
to
the
bitertanol
TRED,
which
are
available
on
the
Internet
at
www.
regulations.
gov
under
docket
number
EPA­
HQ­
OPP­
2005­
0491
and
in
the
public
docket
for
viewing.

The
Agency
is
issuing
this
TRED
document
for
bitertanol
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
bitertanol
tolerance
meets
the
new
safety
standards
established
by
FFDCA,
as
amended
by
FQPA.
This
risk
assessment
for
bitertanol
includes
evaluation
of
potential
susceptibility
to
infants
and
children,
and
dietary
exposure
to
adults
and
children.
EPA
also
considered
potential
cumulative
risks
for
bitertanol
and
other
substances
sharing
a
common
mechanism
of
toxicity,
as
well
as
potential
endocrine
effects
associated
with
bitertanol.

EPA
has
determined
that
risk
from
exposure
to
bitertanol
is
within
its
own
"
risk
cup."
In
other
words,
EPA
is
able
to
conclude
today
that
the
tolerance
for
bitertanol
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
exposures.
Because
there
are
no
existing
registrations
for
the
use
of
bitertanol
in
the
U.
S.,
only
acute
and
chronic
dietary
(
food)
assessments
were
conducted
for
potential
exposure
to
bitertanol
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
bitertanol
"
fit"
within
the
individual
risk
cup
for
this
chemical.
The
Agency's
risk
assessment
conclusions
are
summarized
below.

FQPA
Safety
Factor
and
Database
Considerations.
The
FFDCA,
as
amended
by
the
FQPA,
directs
the
Agency
to
use
an
additional
tenfold
(
10X)
safety
factor
(
SF)
to
take
into
account
potential
pre­
and
postnatal
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
demonstrates
that
the
resulting
level
of
exposure
would
be
safe
for
infants
and
children.

In
submitted
developmental
toxicity
studies,
effects
were
seen
at
the
same
dose
levels
as
maternal
toxicity.
There
was
evidence
of
malformations
and
post­
implantation
loss
at
high
doses
in
developmental
toxicity
studies,
but
no
quantitative
susceptibility
and
No
Observed
Adverse
Effect
Levels
(
NOAELs)
were
clearly
defined.
In
rabbits
there
were
three
developmental
studies
which,
when
combined,
clearly
delineated
developmental
toxicity
in
the
rabbit.
Although
there
were
some
deficiencies
in
the
rat
reproduction
study,
the
study
is
considered
acceptable
and
indicates
that
there
are
adequately
defined
NOAELs
and
no
evidence
of
susceptibility.
There
is
no
residual
uncertainty
for
pre­
and
postnatal
toxicity
based
on
the
submitted
developmental
and
reproduction
studies.

Because
there
is
no
residual
uncertainty
with
respect
to
pre­
and
postnatal
toxicity
based
on
the
submitted
developmental
and
reproduction
studies,
the
Special
FQPA
SF
is
reduced
to
1X.
There
is
some
uncertainty
for
potential
neurotoxicity
based
on
some
literature
studies.
Because
acute
and
subchronic
neurotoxicity
studies
are
not
available,
a
10X
database
uncertainty
factor
(
UFDB)
is
retained
to
account
for
the
lack
of
data.
Page
5
of
7
Dietary
Risks
(
food).
Acute
and
chronic
dietary
(
food)
risk
assessments
were
conducted
using
Dietary
Exposure
Evaluation
Model
(
DEEM­
FCID
 
,
Version
2.03).
These
Tier
1
assessments
are
based
on
an
assumption
of
100%
crop
treated,
the
proposed
maximum
residue
tolerance
of
0.5
parts
per
million
(
ppm)
on
whole
bananas,
and
a
default
processing
factor
of
3.9x
(
DEEM,
Version
7.81)
to
assess
concentration
of
potential
bitertanol
residues
in
dried
bananas.
Risk
to
each
population
group
is
measured
by
a
population
adjusted
dose
(
PAD),
which
is
the
dose
predicted
to
result
in
no
unreasonable
health
effects
to
any
human
subpopulation,
including
sensitive
members
of
such
subpopulations.
The
acute
PAD
(
aPAD)
is
the
dose
at
which
a
person
could
be
exposed
on
any
given
day,
and
the
chronic
PAD
(
cPAD)
is
the
dose
at
which
a
person
could
be
exposed
over
the
course
of
a
lifetime,
with
no
expected
adverse
health
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
bitertanol
residues
in
food
are
low
and
below
the
Agency's
level
of
concern.
An
acute
dietary
risk
assessment
was
conducted
only
for
females
13­
49
years
old,
with
estimated
exposures
representing
2%
of
the
aPAD
at
the
95th
exposure
percentile.
For
the
general
population,
no
acute
dietary
endpoint
was
selected
because
effects
attributable
to
a
single
dose
were
not
seen
in
the
available
data.
Chronic
dietary
risk
assessments
were
conducted
for
the
general
U.
S.
population
and
various
population
subgroups,
including
exposure
to
infants
and
children.
The
resulting
chronic
dietary
exposure
estimates
were
9%
of
the
cPAD
for
the
general
U.
S.
population,
and
43%
of
the
cPAD
for
the
highest­
exposed
population
subgroup,
children
1­
2
years
old.

Because
there
are
no
bitertanol
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.

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
bitertanol
and
any
other
substances,
and
bitertanol
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
bitertanol
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,
Page
6
of
7
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).

In
the
available
toxicity
studies
on
bitertanol,
there
was
no
estrogen,
androgen,
and/
or
thyroid­
mediated
toxicity.
A
potential
hormonal
effect
was
seen
in
a
subchronic
dog
study,
but
not
in
chronic
dog
studies.
The
hormonal
effect
in
the
chronic
dog
studies
suggests
that
the
effect
was
specific
to
the
dogs
tested
in
the
subchronic
study,
and
not
as
a
result
of
bitertanol
exposure.
However,
the
reason
for
the
difference
in
hormonal
effect
between
the
dog
studies
is
unknown.
When
additional
appropriate
screening
and/
or
testing
protocols
being
considered
under
the
Agency's
EDSP
have
been
developed,
bitertanol
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
§
180.457
The
existing
tolerance
for
residues
of
bitertanol
per
se,
established
under
40
CFR
§
180.457
is
listed
in
Table
1.
The
current
tolerance
expression
listed
in
40
CFR
§
180.457
is
"
beta­([
1,1'­
biphenyl]­
4­
yloxy)­
alpha­(
1,1­
dimethylethyl)­
1H­
1,2,4­
triazole­
1­
ethanol."
The
Codex
Alimentarius
Commission
has
established
a
maximum
residue
level
(
MRL)
for
bitertanol
per
se
in/
on
bananas
at
0.5
ppm.
The
Agency
recommends
that
the
U.
S.
tolerance
expression
be
revised
to
0.5
ppm,
to
harmonize
its
tolerances
with
those
established
by
the
Codex
Alimentarius
Commission.
The
proposed
increased
tolerance
of
0.5
ppm
was
included
in
the
dietary
assessment,
and
did
not
result
in
any
risks
of
concern.
It
is
EPA's
policy
to
harmonize
its
tolerances
with
the
levels
established
by
Codex
provided
that
the
Agency
has
sufficient
information
to
make
a
determination
that
the
Codex
MRLs
will
be
protective
of
the
health
of
the
U.
S.
public
and
meet
FFDCA
standards.

Table
1:
Tolerance
Summary
for
Bitertanol
Commodity
Established
Tolerance
(
ppm)
Reassessed
Tolerance
(
ppm)
Comments
[
Correct
Commodity
Definition]

Banana
(
whole)
0.2
ppm
0.5
ppm
Tolerance
should
be
increased
to
0.5
ppm
to
harmonize
with
Codex
MRLs.
[
Banana]

III.
Data
Gaps
The
Agency
has
concluded
that
the
database
for
bitertanol
is
substantially
complete,
but
has
identified
some
data
gaps.
There
are
no
U.
S.
registrations
for
bitertanol.
A
Data
Call­
In
notice
for
this
additional
data
will
not
be
issued
because
these
data
are
not
expected
to
change
the
regulatory
conclusions
of
the
bitertanol
TRED
described
in
this
document.
Page
7
of
7
Although
acute
and
subchronic
neurotoxicity
data
gaps
exist,
a
10X
UFDB
has
been
used
in
both
chronic
and
acute
dietary
assessments
to
account
for
the
absence
of
these
data.
Additional
missing
data
pertain
to
residue
field
trials.
However,
the
Agency
does
not
view
these
data
as
critical
to
the
continuation
of
the
existing
tolerance
because
exposure
assumptions
used
in
the
risk
assessments
were
highly
conservative
(
i.
e.,
100%
crop
treated;
default
residue
concentration
factor
of
3.9x
for
dried
bananas;
and
assumption
of
residues
at
0.5
ppm
to
harmonize
with
Codex,
even
though
available
field
trials
indicate
that
maximum
residues
were
detected
at
less
than
0.2
ppm).