Company
Notice
of
Filings
for
Pesticide
Petitions
(
Dated:
7/
20/
04)

EPA
Antimicrobials
Division
contact:[
Velma
Noble,
703­
308­
6233]

[
INSTRUCTIONS:
Please
utilize
this
outline
in
preparing
tolerance
petition
submissions.
In
cases
where
the
outline
element
does
not
apply
please
insert
"
NA­
Remove"
and
maintain
the
outline.
The
comment
notes
that
appear
on
the
left
margin
represent
hidden
typesetting
codes
designed
to
expedite
the
processing
of
the
FEDERAL
REGISTER
document.
Please
do
not
remove
or
alter
these
codes
or
change
the
margins
in
your
submission.
Simply
type
the
information
requested
starting
after
the
heading.

1.
[
Intralytix,
Inc.]

PP
[
]

EPA
has
received
a
pesticide
petition
(
PP
[
])
from
[
Intralytix,
Inc.],
[
323
W.
Camden
Street,
Baltimore,
MD
21201],
proposing
pursuant
to
section
408(
d)
of
the
Federal
Food,
Drug
and
Cosmetic
Act,
21
U.
S.
C.
346a(
d),
to
amend
40
CFR
Part
180.

2.
to
establish
an
temporary
exemption
from
the
requirement
of
a
tolerance
for
[
Listeria
specific
bacteriophages]
when
used
in
accordance
with
good
manufacturing
practice
as
the
active
ingredient
in
an
antimicrobial
pesticide
formulation
provided
that
the
substance
is
applied
on
a
semi­
permanent
or
permanent
food­
contact
surface
(
other
than
being
applied
on
food
packaging)
with
adequate
draining
before
contact
with
food.
EPA
has
determined
that
the
petition
contains
data
or
information
regarding
the
elements
set
forth
in
section
408(
d)(
2)
of
the
FFDCA;
however,
EPA
has
not
fully
evaluated
the
sufficiency
of
the
submitted
data
at
this
time
or
whether
the
data
supports
granting
of
the
petition.
Additional
data
may
be
needed
before
EPA
rules
on
the
petition.

A.
Residue
Chemistry
1.
Metabolism
Data
[
Metabolism
studies
are
not
applicable
since
the
subject
active
ingredient
is
a
bacterial
virus].

2.
Analytical
method.
[
Since
the
petitioner
has
requested
a
tolerance
exemption,
a
residue
analytical
method
is
not
pertinent].

3.
Magnitude
of
residues.
[
No
residue
studies
have
been
conducted
since
bacteriophages
are
ubiquitous
in
the
environment
and
are
commonly
found
in
food.
Moreover,
the
amount
of
phage
2
residue
remaining
on
the
treated
surface
from
the
use
of
the
Listeria
specific
bacteriophages
will
be
a
small
fraction
of
the
phage
levels
typically
found
in
the
environment].

B.
Toxicological
Profile
1.
Acute
toxicity.
[
The
acute
oral
LD
50
of
a
preparation
(
LMP­
102
 
)
containing
a
mixture
of
six
Listeria
specific
bacteriophages
is
greater
than
5,000
mg/
kg.
Accordingly,
Listeria
specific
bacteriophages
can
be
considered
non­
toxic
by
the
oral
route
of
exposure.

The
petitioner
is
requesting
that
the
Agency
waive
all
other
toxicity/
pathogenicity
studies
for
Listeria
specific
bacteriophages
for
the
following
reasons:

1.
The
ubiquity
and
safety
of
bacteriophages
have
been
well­
established
in
the
published
literature.
There
are
no
reports
in
the
published
literature
of
any
adverse
effects
of
concern
that
have
occurred
as
a
result
of
human
or
animal
exposure
to
bacteriophages.

2.
The
biology
of
bacteriophages
has
been
exhaustively
studied.
These
studies
have
clearly
shown
that
bacteriophages
are
obligate
intracellular
parasites
of
bacteria
and
are
not
infectious
to
humans
or
other
mammals.

3.
Bacteriophages
are
common
commensals
of
the
human
gut
and
they
are
likely
to
play
an
important
role
in
regulating
the
diversity
and
population
of
various
bacteria
in
human
GI
tracts.
Bacteriophages
capable
of
infecting
E.
coli,
Bacteroides
fragilis
and
various
Salmonella
serotypes
have
been
isolated
from
human
fecal
specimens
in
concentrations
as
high
as
105
PFU/
100
g
of
feces.
Recent
data
based
on
metagenomic
analyses
(
using
shotgun
sequencing)
of
an
uncultured
viral
community
from
human
feces
suggests
that
bacteriophages
are
the
second
most
abundant
category
in
the
uncultured
fecal
library.

4.
Bacteriophages
have
been
used
therapeutically
in
humans
for
more
than
80
years
without
any
recorded
adverse
effects.
In
addition,
bacteriophages
have
also
been
administered
to
humans
for
nontherapeutic
purposes
without
any
recorded
adverse
effects.
For
example,
bacteriophage
preparations
have
been
used
extensively
to
monitor
humoral
immune
function
in
humans].

2.
Genotoxicty.
[
NA­
Remove].

3.
Reproductive
and
developmental
toxicity.
[
NA­
Remove].

4.
Subchronic
toxicity.
[
NA­
Remove].

5.
Chronic
toxicity.
[
NA­
Remove].
3
6.
Animal
metabolism.
[
NA­
Remove].

7.
Metabolite
toxicology.
[
NA­
Remove].

8.
Endocrine
disruption.
[
NA­
Remove].

C.
Aggregate
Exposure
1.
Dietary
exposure.
[
Due
to
the
low
application
rate
of
the
bacteriophage
preparation
(
LMP­
102)
containing
Listeria
specific
bacteriophages
and
the
limited
use
(
treatment
of
food­
contact
surfaces
in
food­
processing
plants)
dietary
exposure
to
the
subject
bacteriophages
is
anticipated
to
be
negligible.
In
addition,
any
phage
residue
that
transfers
to
food
will
likely
be
destroyed
as
the
food
is
further
processed
since
bacteriophages
are
inactivated
by
heat].

2.
Food.
[
As
noted
above,
potential
food
residues
of
Listeria
specific
bacteriophages
from
the
use
of
LMP­
102
are
unlikely].

3.
Drinking
water.
[
No
drinking
water
exposure
will
occur
from
the
proposed
use
of
LMP­
102
since
the
use
is
limited
to
treatment
of
food­
contact
surfaces
in
food­
processing
plants].

4.
Non­
dietary
exposure.
[
The
only
non­
dietary
exposure
that
will
occur
from
the
use
of
the
subject
bacteriophages
is
to
applicators
in
food­
processing
plants.
Intralytix
expects
that
this
exposure
will
be
insignificant].

[
Based
on
the
above,
Intralytix
anticipates
that
the
aggregate
exposure
from
the
subject
use
of
Listeria
specific
bacteriophages
will
be
inconsequential].

D.
Cumulative
Effects
[
No
cumulative
effects
are
expected
from
the
subject
use
of
Listeria
specific
bacteriophages].

E.
Safety
Determination
4
1.
U.
S.
population.
[
The
subject
use
of
Listeria
specific
bacteriophages
is
not
anticipated
to
present
any
risks
of
concern
to
the
U.
S.
population
since:
(
i)
bacteriophages
are
ubiquitous
in
the
environment
and
in
food;
(
ii)
there
are
no
reports
of
any
adverse
effects
to
humans
from
exposure
to
bacteriophages.
Consequently,
there
is
a
reasonable
certainty
that
no
harm
to
the
U.
S.
population,
including
infants
and
children,
will
result
from
exposure
to
Listeria
specific
bacteriophages].

2.
Infants
and
children.
[
There
are
no
unique
concerns
or
risks
to
infants
and
children
that
may
be
exposed,
in
the
diet,
to
the
subject
bacteriophages].

F.
International
Tolerances
[
There
are
no
approved
CODEX
Alimentarium
Commission
Maximum
Residue
Levels
(
MRLs)
established
for
residues
of
Listeria
specific
bacteriophages].
