Document ID: EPA-HQ-OPP-2006-0325-0002
Agency: epa
Document Type: Supporting & Related Material
Title: 
Posted Date: 2006-04-19T04:00Z

FILE
NAME:
biopetit.
wpt
(
1/
1/
2006)
(
xml)

Number:
P4
ATTENTION:

All
commodity
terms
must
comply
with
the
Food
and
Feed
Commodity
Vocabulary
database
(
http://
www.
epa.
gov/
pesticides/
foodfeed/).

All
text
in
blue
font
(
instructions
for
preparing
the
document),
should
be
removed
prior
to
sending
the
document
to
the
Federal
Register
Staff.
Instructional
text
and
prompts
in
green
font
should
also
be
removed.

EPA
BIOPESTICIDES
AND
POLLUTION
PREVENTION
DIVISION
COMPANY
NOTICE
OF
FILING
TEMPLATE
FOR
PESTICIDE
PETITIONS
PUBLISHED
IN
THE
FEDERAL
REGISTER
(
1/
1/
2006)

EPA
Biopesticides
and
Pollution
Prevention
Division
contact:
[
insert
name
and
telephone
number
with
area
code]

INSTRUCTIONS:
Use
this
template
in
preparing
your
notice
of
filing
for
your
company's
pesticide
petition.
In
cases
where
the
outline
element
does
not
apply,
insert
"
NA­
Remove"
and
maintain
the
outline.
The
comment
balloons
appearing
in
the
left
margin
contain
Government
Printing
Office
(
GPO)
typesetting
codes
which
expedite
the
Federal
Register
(
FR)
publication
process
at
EPA
for
the
FR
document
containing
your
company's
pesticide
petition.
In
the
template,
do
not
remove
or
alter
the
comment
balloons;
change
the
margins,
font,
or
format;
or
use
the
WordPerfect
comment
function.
Follow
the
instructions
that
appear
italicized,
color
coded,
and
bracketed.

SUBMISSION:
E­
mail
the
completed
template
to:
hollis.
linda@
epa.
gov.

TEMPLATE:

[
Valent
BioSciences
Corp.]

[
6F7035]

EPA
has
received
a
pesticide
petition
[
6F7035]
from
[
Valent
BioSciences
Corp.]
,
[
870
Technology
Way,
Libertyville,
IL],
proposing
pursuant
to
section
408(
d)
of
the
Federal
Food,
Drug,
and
Cosmetic
Act
(
FFDCA),
21
U.
S.
C.
346a(
d),
to
amend
40
CFR
part
180
2
Options
(
pick
one)

1.
by
establishing
a
tolerance
for
residues
of
the
NA­
Remove
2.
to
establish
an
exemption
from
the
requirement
of
a
tolerance
for
the
NA­
Remove
3.
to
establish
an
amendment/
expansion
of
an
existing
tolerance
exemption
for
the
Options
(
pick
one)

1.
microbial
pesticide
[
NA­
Remove]

2.
biochemical
pesticide
[
6­
Benzyladenine]

3.
plant­
pesticide
[
NA­
Remove]
in
or
on
[
pear].

Pursuant
to
section
408(
d)(
2)(
A)(
i)
of
the
FFDCA,
as
amended,
[
Valent
BioSciences
Corp.]
has
submitted
the
following
summary
of
information,
data,
and
arguments
in
support
of
their
pesticide
petition.
This
summary
was
prepared
by
[
Valent
BioSciences
Corp.]
and
EPA
has
not
fully
evaluated
the
merits
of
the
pesticide
petition.
The
summary
may
have
been
edited
by
EPA
if
the
terminology
used
was
unclear,
the
summary
contained
extraneous
material,
or
the
summary
unintentionally
made
the
reader
conclude
that
the
findings
reflected
EPA's
position
and
not
the
position
of
the
petitioner.

I.
[
Valent
BioSciences
Corp.]
Petition
Summary
[
6F7035]

A.
Product
name
and
Proposed
Use
Practices
[
6­
Benzyladenine
is
a
naturally
occurring
plant
growth
regulator
used
on
certain
fruit
and
nut
trees
and
certain
ornamental
lily
tubers.
In
January
1990,
the
Agency
classified
N6­
benzyladenine
as
a
biochemical
pesticide
because
it
resembles
natural
plant
regulators
and
it
displays
a
nontoxic
mode
of
action.
The
new
use
being
proposed
for
6­
benzyladenine
(
6­
BA)
is
as
an
effective
stand­
alone
fruitlet
thinner
when
applied
to
pears
in
the
post­
bloom
period
at
an
application
rate
not
to
exceed
182
grams
active
ingredient/
acre/
season
(
g/
ai/
acre/
season).
6­
benzyladenine
has
also
been
shown
to
directly
increase
cell
division
of
treated
fruit,
resulting
in
improvements
in
fruit
size
over
what
would
be
expected
from
the
normal
thinning
effect.
The
frequency
and
timing
of
application
will
vary
according
to
the
specific
growing
conditions
being
treated.
]

B.
Product
Identity/
Chemistry
3
1.
Identity
of
the
pesticide
and
corresponding
residues.
[
6­
Benzyladenine
[
N­
(
phenylmethyl)­
1H­
purin­
6­
amine]
has
been
tested
and
residue
data
generated
has
been
provided
to
EPA
by
Valent
BioSciences
Corporation.]

2.
Magnitude
of
residue
at
the
time
of
harvest
and
method
used
to
determine
the
residue.
[
Trials
conducted
in
various
states
(
NY,
PA,
VA,
MI,
OR
and
WA)
and
on
various
apple
cultivars,
support
the
proposed
tolerance
exemption.
This
data
has
been
further
supported
by
numerous
trials
carried
out
internationally.
Residue
levels
following
the
maximum
number
(
4)
of
applications
on
apple
were
very
close
to
the
limit
of
quantitation
(
LOQ)
of
5
parts
per
billion
(
ppb)
at
normal
harvest,
which
averaged
80
days
after
the
last
application.
Trials
indicate
rapid
degradation
of
6­
BA
residues
among
all
the
apple
varieties
and
geographies
evaluated.
Both
pears
and
apples
belong
to
Crop
Group
11:
Pome
Fruit
Group.
The
thinning
use
of
6­
Benzyladenine
on
pears
has
the
exact
same
timing,
uses
the
exact
same
dose
rate
and
has
the
same
number
of
days
to
harvest.
Pears
tend
to
be
grown
in
the
same
geographical
and
climatic
environment
as
apples.
The
analytical
methods
for
detection
of
6­
BA
in
apple
raw
agricultural
and
processed
commodities
are
comprised
of
extraction,
cleanup
on
a
strong
cation
exchange
(
SCX)
solid­
phase
extraction
cartridge,
derivatisation
and
quantitation
by
gas
chromatography.
These
were
developed
by
Valent
BioSciences
Corp.
and
submitted
to
EPA,
constituting
a
practical
analytical
method
for
detecting
and
measuring
levels
of
6­
BA
in
or
on
commodities,
with
a
limit
of
quantitation
(
LOQ)
of
0.005
ppm
that
allows
for
monitoring
of
food,
with
the
residues
at
or
above
the
LOQ.]

3.
A
statement
of
why
an
analytical
method
for
detecting
and
measuring
the
levels
of
the
pesticide
residue
are
not
needed.
[
Usually,
a
request
for
an
exemption
from
the
requirement
of
a
tolerance
is
not
accompanied
by
residue
data
and
an
analytical
method..
The
information
provided
on
apples
demonstrates
that
any
residue
is
detected
at
levels
very
close
to
the
LOQ.
Although
a
numeric
tolerance
could
be
established,
it
would
be
very
difficult
to
enforce,
as
demonstrated
by
the
risk
characterization.
Valent
BioSciences
Corporation
proposes
that
the
submitted
apple
residue
data
and
analytical
method
support
their
conclusion
that
there
is
a
reasonable
certainty
that
no
harm
to
humans
or
the
environment
will
result
from
the
use
of
6­
BA
on
pears.
]

C.
Mammalian
Toxicological
Profile
[
1.
Acute
toxicity.
The
oral
LD
50
of
6­
Benzyladenine
is
estimated
by
probit
analysis
at
1.3
g/
kg
in
the
rat.
The
dermal
LD
50
in
the
rabbit
is
>
5.0
g/
kg.
The
acute
inhalation
LC
50
in
the
rat
is
5.2
mg/
l/
hour.
A
primary
eye
irritation
study
in
the
rabbit
showed
moderate
conjunctival
effects
which
cleared
within
7
days.
A
dermal
irritation
study
in
the
rabbit
showed
slight
dermal
irritation,
which
lasted
for
5
days.
Sensitization
potential
has
been
examined,
and
6­
Benzyladenine
(
99%
pure)
was
demonstrated
not
to
be
a
dermal
sensitizer
in
guinea
pigs
under
conditions
of
the
study.
2.
Genotoxicity.
Mutagenicity
studies
including
Ames
Test,
mouse
micronucleus
assay,
and
unscheduled
DNA
4
synthesis
assay
in
rat
were
negative
for
mutagenic
effects.
3.
Developmental
toxicity
Developmental
toxicity
in
rats
fed
6­
Benzyladenine
(
99%
pure)
was
manifested
as
significantly
decreased
fetal
body
weight,
increased
incidence
of
hydrocephalas
and
unossified
sternbrae,
incompletely
ossified
phalanges,
and
malaligned
sternbrae
at
175
mg/
kg/
day.

Maternal
toxicity
was
also
observed
at
175
mg/
kg/
day,
which
was
manifested
as
significantly
decreased
body
weight,
weight
gain,
and
food
consumption.
Thus
the
NOAEL
and
LOAEL
for
maternal
and
developmental
toxicity
was
50
and
175
mg/
kg/
day,
respectively.

4.
Subchronic
Toxicity
6­
Benzyladenine
(
99%
pure)
fed
to
rats
for
13
weeks
produced
decreased
weight
gain
at
1500
and
5000
PPM
(
121
and
322
mg/
kg/
day)
in
females,
and
5000
ppm
(
295
mg/
kg/
day)
in
males.
This
decreased
weight
gain
appeared
to
be
related
to
decreased
food
consumption.
Serum
alkaline
phosphatase
activity
and
blood
urea
nitrogen
levels
were
increased
in
both
sexes
receiving
5000
ppm;
thus
the
NOAEL
was
1500
ppm
(
approximately
111
mg/
kg/
day
in
both
sexes
combined)
and
LOAEL
was
5000
ppm
(
approximately
304
mg./
kg/
day
in
both
sexes),
based
on
the
decreased
body
weight
gain,
food
consumption,
increased
blood
urea
nitrogen,
and
minimal
histological
changes
in
the
kidneys.

5.
Reproductive
Toxicity
A
two­
generation
reproduction
study
consisted
in
administering
6­
Benzyladenine
in
diet
without
interruption,
covering
the
periods
of
pre­
mating,
mating,
pregnancy,
lactation
until
termination
for
both
male
and
female
parent
rats.
Mating
performance,
duration
of
gestation,
and
litter
size
and
mortality
were
similar
in
all
groups.
There
were
no
histological
findings
on
the
reproductive
organs
or
abnormalities
of
the
sperm
that
were
considered
to
be
related
to
treatment.
The
NOAEL
for
reproductive
findings
was
400
ppm
(
approximately
30
and
45
mg/
kg
bw/
day
for
males
and
females,
respectively),
although
effects
noted
at
the
higher
levels
were
confined
to
reduced
weight
gains
of
the
pup.

]

D.
Aggregate
Exposure
1.
Dietary
exposure.

i.
Food.
[
In
conducting
this
exposure
assessment,
Valent
BioSciences
Corp.
used
very
conservative
assumptions,
100
percent
of
all
commodities
were
assumed
to
be
treated,
and
those
residues
would
be
at
twice
the
LOQ
­­
which
result
in
a
large
overestimate
of
human
exposure.
The
analysis
assumes
that
all
residues
have
the
same
magnitude,
and
the
treated
commodity
is
100%
of
a
daily
diet..
Thus,
in
making
a
safety
determination
for
these
tolerance
exemptions,
Valent
BioSciences
Corp.
took
into
account
this
very
conservative
exposure
assessment.
The
last
application
precedes
harvest
by
approximately
2.5
months
in
pears,
therefore
the
potential
for
5
dietary
exposure
is
considered
negligible
by
Valent
BioSciences
Corp..
]

ii.
Drinking
water.
[
The
proposed
use
on
pears
is
not
expected
to
add
potential
exposure
to
drinking
water.
Soil
leaching
studies
have
suggested
that
6BA
is
relatively
immobile,
absorbing
to
sediment.
Residues
reaching
surface
waters
from
field
runoff
should
quickly
absorb
to
sediment
particles
and
be
partitioned
from
the
water
column.
Soil
metabolism
studies
give
DT50
of
3­
10
days
for
6­
benzyladenine.
6­
benzyladenine
also
has
low
solubility
in
water,
0.061
mg/
ml
and
detections
in
groundwater
are
not
expected.
.
Valent
BioSciences
Corp.
concludes
that
together
these
data
indicate
that
residues
are
not
expected
in
drinking
water.]

2.
Non­
dietary
exposure.
[
The
proposed
uses
involve
application
of
6­
BA
to
crops
grown
in
an
agricultural
environment.
The
only
non­
dietary
exposure
expected
is
that
to
applicators.
However,
the
protective
measures
prescribed
by
the
product's
label
are
expected
to
be
adequate
to
minimize
exposure
and
protect
applicators
of
the
chemical]

E.
Cumulative
Exposure
[
No
cumulative
adverse
effects
are
expected
from
long­
term
exposure
to
this
chemical.
There
is
no
reliable
information
to
indicate
that
toxic
effects
produced
by
6­
BA
would
be
cumulative
with
those
of
any
other
pesticide
chemical]

F.
Safety
Determination
1.
U.
S.
population.
[
Chronic
dietary
exposure
estimates
for
apple
and
pistachio
were
conducted
for
the
overall
US
population
and
25
population
subgroups,
including
infants
and
children.
These
estimated
daily
intakes
were
compared
against
a
chronic
population
adjusted
dose
(
cPAD)
based
on
a
No
Observed
Adverse
Effect
Level
(
NOAEL)
of
50
mg/
kg
bw/
day
from
a
developmental
study
in
rats.
To
account
for
intra­
and
inter­
species
variation
and
the
use
of
an
acute
toxicological
endpoint
for
a
chronic
assessment,
an
uncertainty
factor
of
1000
was
applied
to
the
acute
NOAEL.
This
resulted
in
a
cPAD
of
0.05
mg/
kg
bw/
day.
Daily
exposure
for
the
overall
US
population
was
estimated
to
be
0.000014mg/
kg
bw/
day,
representing
less
than
0.1%
of
the
estimated
cPAD.
Since
pear
constitutes
a
smaller
consumption
commodity
than
apple
the
cPAD
will
be
than
0.1%.
]

2.
Infants
and
children.
[
Estimated
daily
exposures,
assuming
that
100%
of
the
apple
and
pistachio
commodities
in
the
US
are
treated
with
6­
benzyladenine,
for
the
most
highly
exposed
population
subgroup,
non­
nursing
infants,
was
estimated
to
be
0.000085
mg/
kg
bw/
day,
or
0.2%
of
the
estimated
cPAD.
Since
pear
constitutes
a
smaller
consumption
commodity
than
apple,
the
cPAD
will
be
than
0.2%]

G.
Effects
on
the
Immune
and
Endocrine
Systems
6
[
6­
benzyladenine
is
a
naturally
occurring
cytokinin
which
has
plant
growth
regulator
properties.
There
is
no
indication
that
this
plant
growth
regulator
belongs
to
a
class
of
chemicals
known
or
suspected
of
having
adverse
effects
on
the
immune
and
endocrine
systems.
It
can
be
concluded
that
based
upon
the
existing
toxicology
there
would
be
no
adverse
effects
on
the
immune
or
endocrine
systems
from
the
use
of
6­
benzyladenine.
Last,
there
is
no
evidence
that
6­
benzyladenine
bioaccumulates
in
the
environment.
]

H.
Existing
Tolerances
[
The
biochemical
plant
regulator
6­
benzyladenine
(
6­
BA)
is
exempt
from
the
requirement
of
a
tolerance
in
or
on
apple
at
an
application
rate
of
<=
182
grams
of
active
ingredient
per
acre
per
season,
and
in
or
on
pistachio
at
an
application
rate
of
<=
60
grams
of
active
ingredient
per
acre
per
season.
]

I.
International
Tolerances
[
There
are
no
Codex,
Canadian,
or
Mexican
maximum
residue
limits
for
use
of
6­
benzyladenine
on
pears.]

[
FR
Doc.
06­?????
Filed
??­??­
06;
8:
45
am]
[
BILLING
CODE
6560­
50­
S]