78459
Federal
Register
/
Vol.
67,
No.
247
/
Tuesday,
December
24,
2002
/
Notices
Register
notice
describing
the
electronic
docket
at
67
FR
38102
(
May
31,
2002),
or
go
to
http://
www.
epa.
gov./
edocket.
Title:
NSPS
for
Lime
Manufacturing
(
40
CFR
part
60,
subpart
HH)
(
OMB
Control
No.
2060
 
0063,
EPA
ICR
Number
1167.07).
This
is
a
request
to
renew
an
existing
approved
collection
that
is
scheduled
to
expire
on
January
31,
2003.
Under
the
OMB
regulations,
the
Agency
may
continue
to
conduct
or
sponsor
the
collection
of
information
while
this
submission
is
pending
at
OMB.
Abstract:
The
New
Source
Performance
Standards
(
NSPS)
for
Lime
Manufacturing
Plants
were
proposed
on
May
3,
1977
and
promulgated
on
April
26,
1984.
These
standards
apply
to
each
rotary
lime
kiln
used
in
lime
manufacturing,
which
commenced
construction,
modification
or
reconstruction
after
May
3,
1977.
The
standards
do
not
apply
to
facilities
used
in
the
manufacture
of
lime
at
kraft
pulp
mills.
The
purpose
of
this
NSPS
is
to
control
the
emissions
of
particulate
matter
(
PM)
from
lime
manufacturing
plants,
specifically
from
the
operation
of
the
rotary
lime
kilns.
The
standards
limit
particulate
emissions
to
0.30
kilogram
per
megagram
(
0.60
lb/
ton)
of
stone
feed,
and
limit
opacity
to
15%
when
exiting
from
a
dry
emission
control
device.
This
information
is
being
collected
to
assure
compliance
with
40
CFR
part
60,
subpart
HH.
There
are
three
types
of
reporting
requirements
for
owners
or
operators
of
facilities
under
this
NSPS:
(
1)
Notifications
(
e.
g.,
notice
for
new
construction
or
reconstruction,
anticipated
and
actual
startup
dates,
initial
performance
test,
and
demonstration
of
the
CMS);
(
2)
a
report
on
the
results
of
the
performance
test;
and
(
3)
semiannual
reports
of
instances
of
occurrence
and
duration
of
any
startup,
shutdown,
or
malfunctions.
The
purpose
of
the
notifications
are
to
inform
the
Agency
or
delegated
authority
when
a
source
becomes
subject
to
this
standard.
Performance
tests
are
conducted
to
ensure
that
the
new
plants
operate
within
the
boundaries
outlined
in
the
standard.
The
semiannual
reports
are
used
for
problem
identification,
as
a
check
on
source
operation
and
maintenance,
and
for
compliance
determinations.
Under
this
standard
the
data
collected
by
the
affected
industry
is
retained
at
the
facility
for
a
minimum
of
two
years
and
made
available
for
inspection
by
the
Administrator.
The
Administrator
has
judged
that
PM
emissions
from
lime
manufacturing
plants
cause
or
contribute
to
air
pollution
that
may
reasonably
be
anticipated
to
endanger
public
health
or
welfare.
Owners/
operators
of
lime
manufacturing
plants
must
notify
EPA
of
construction,
modification,
startups,
shutdowns,
malfunctions
and
performance
test
dates,
as
well
as
provide
reports
on
the
initial
performance
test
and
annual
excess
emissions.
The
industry
costs
associated
with
the
information
collection
activity
in
the
standards
are
capital
costs
and
O&
M
costs
associated
with
continuous
emissions
monitoring
and
labor
costs
associated
with
recordkeeping
and
reporting.
In
order
to
ensure
compliance
with
the
standards
promulgated
to
protect
public
health,
adequate
reporting
and
recordkeeping
is
necessary.
In
the
absence
of
such
information,
enforcement
personnel
would
be
unable
to
determine
whether
the
standards
are
being
met
on
a
continuous
basis,
as
required
by
the
Clean
Air
Act.
An
agency
may
not
conduct
or
sponsor,
and
a
person
is
not
required
to
respond
to,
a
collection
of
information
unless
it
displays
a
currently
valid
OMB
control
number.
The
OMB
control
numbers
for
EPA's
regulations
are
listed
in
40
CFR
part
9
and
48
CFR
chapter
15,
and
are
identified
on
the
form
and/
or
instrument,
if
applicable.
Burden
Statement:
The
annual
public
reporting
and
recordkeeping
burden
for
this
collection
of
information
is
estimated
to
average
42
hours
per
response.
Burden
means
the
total
time,
effort,
or
financial
resources
expended
by
persons
to
generate,
maintain,
retain,
or
disclose
or
provide
information
to
or
for
a
Federal
agency.
This
includes
the
time
needed
to
review
instructions;
develop,
acquire,
install,
and
utilize
technology
and
systems
for
the
purposes
of
collecting,
validating,
and
verifying
information,
processing
and
maintaining
information,
and
disclosing
and
providing
information;
adjust
the
existing
ways
to
comply
with
any
previously
applicable
instructions
and
requirements;
train
personnel
to
be
able
to
respond
to
a
collection
of
information;
search
data
sources;
complete
and
review
the
collection
of
information;
and
transmit
or
otherwise
disclose
the
information.
Respondents/
Affected
Entities:
Lime
Manufacturing
Plants.
Estimated
Number
of
Respondents:
53.
Frequency
of
Response:
On
occasion,
initial,
and
semiannual.
Estimated
Total
Annual
Hour
Burden:
4,434
hours.
Estimated
Total
Annual
Cost:
$
91,500.
Changes
in
the
Estimates:
There
is
an
increase
of
244
hours
in
the
total
estimated
burden
currently
identified
in
the
OMB
Inventory
of
Approved
ICR
Burdens.
This
increase
is
due
to
an
increase
in
the
number
of
existing
facilities
subject
to
this
standard
resulting
from
the
availability
of
more
accurate
data.

Dated:
December
10,
2002.
Oscar
Morales,
Director,
Collection
Strategies
Division.
[
FR
Doc.
02
 
32399
Filed
12
 
23
 
02;
8:
45
am]

BILLING
CODE
6560
 
50
 
P
ENVIRONMENTAL
PROTECTION
AGENCY
[
OPP
 
2002
 
0283;
FRL
 
7277
 
5]

Bronopol;
Notice
of
Filing
a
Pesticide
Petition
to
Establish
a
Tolerance
for
a
Certain
Pesticide
Chemical
in
or
on
Food
AGENCY:
Environmental
Protection
Agency
(
EPA).
ACTION:
Notice.

SUMMARY:
This
notice
announces
the
initial
filing
of
a
pesticide
petition
proposing
the
establishment
of
regulations
for
residues
of
a
certain
pesticide
chemical
in
or
on
various
food
commodities.
DATES:
Comments,
identified
by
docket
ID
number
OPP
 
2002
 
0283,
must
be
received
on
or
before
January
23,
2003.
ADDRESSES:
Comments
may
be
submitted
electronically,
by
mail,
or
through
hand
delivery/
courier.
Follow
the
detailed
instructions
as
provided
in
Unit
I.
of
the
SUPPLEMENTARY
INFORMATION.

FOR
FURTHER
INFORMATION
CONTACT:
Bipin
Gandhi,
Registration
Division
(
7505C),
Office
of
Pesticide
Programs,
Environmental
Protection
Agency,
1200
Pennsylvania
Ave.,
NW.,
Washington,
DC
20460
 
0001;
telephone
number:
(
703)
308
 
8380;
e­
mail
address:
gandhi.
bipin@
epa.
gov.

SUPPLEMENTARY
INFORMATION:

I.
General
Information
A.
Does
this
Action
Apply
to
Me?

You
may
be
potentially
affected
by
this
action
if
you
are
an
agricultural
producer,
food
manufacturer,
pesticide
manufacturer,
or
antimicrobial
pesticide
manufacturer.
Potentially
affected
entities
may
include,
but
are
not
limited
to:
 
Industry
(
NAICS
111),
e.
g.,
Crop
production.
 
Industry
(
NAICS
112),
e.
g.,
Animal
production.
 
Industry
(
NAICS
311),
e.
g.,
Food
manufacturing.

VerDate
0ct<
31>
2002
19:
49
Dec
23,
2002
Jkt
200001
PO
00000
Frm
00050
Fmt
4703
Sfmt
4703
E:\
FR\
FM\
24DEN1.
SGM
24DEN1
78460
Federal
Register
/
Vol.
67,
No.
247
/
Tuesday,
December
24,
2002
/
Notices
 
Industry
(
NAICS
32532),
e.
g.,
Pesticide
manufacturing.
 
Industry
(
NAICS
32561),
e.
g.,
Antimicrobial
pesticide.
This
listing
is
not
intended
to
be
exhaustive,
but
rather
provides
a
guide
for
readers
regarding
entities
likely
to
be
affected
by
this
action.
Other
types
of
entities
not
listed
in
this
unit
could
also
be
affected.
The
North
American
Industrial
Classification
System
(
NAICS)
codes
have
been
provided
to
assist
you
and
others
in
determining
whether
this
action
might
apply
to
certain
entities.
If
you
have
any
questions
regarding
the
applicability
of
this
action
to
a
particular
entity,
consult
the
person
listed
under
FOR
FURTHER
INFORMATION
CONTACT.

B.
How
Can
I
Get
Copies
of
this
Document
and
Other
Related
Information?

1.
Docket.
EPA
has
established
an
official
public
docket
for
this
action
under
docket
identification
(
ID)
number
OPP
 
2002
 
0283.
The
official
public
docket
consists
of
the
documents
specifically
referenced
in
this
action,
any
public
comments
received,
and
other
information
related
to
this
action.
Although
a
part
of
the
official
docket,
the
public
docket
does
not
include
Confidential
Business
Information
(
CBI)
or
other
information
whose
disclosure
is
restricted
by
statute.
The
official
public
docket
is
the
collection
of
materials
that
is
available
for
public
viewing
at
the
Public
Information
and
Records
Integrity
Branch
(
PIRIB),
Rm.
119,
Crystal
Mall
#
2,
1921
Jefferson
Davis
Hwy.,
Arlington,
VA.
This
docket
facility
is
open
from
8:
30
a.
m.
to
4
p.
m.,
Monday
through
Friday,
excluding
legal
holidays.
The
docket
telephone
number
is
(
703)
305
 
5805.
2.
Electronic
access.
You
may
access
this
Federal
Register
document
electronically
through
the
EPA
Internet
under
the
``
Federal
Register''
listings
at
http://
www.
epa.
gov/
fedrgstr/.
An
electronic
version
of
the
public
docket
is
available
through
EPA's
electronic
public
docket
and
comment
system,
EPA
Dockets.
You
may
use
EPA
Dockets
at
http://
www.
epa.
gov/
edocket/
to
submit
or
view
public
comments,
access
the
index
listing
of
the
contents
of
the
official
public
docket,
and
to
access
those
documents
in
the
public
docket
that
are
available
electronically.
Although
not
all
docket
materials
may
be
available
electronically,
you
may
still
access
any
of
the
publicly
available
docket
materials
through
the
docket
facility
identified
in
Unit
I.
B.
1.
Once
in
the
system,
select
``
search,''
then
key
in
the
appropriate
docket
ID
number.
Certain
types
of
information
will
not
be
placed
in
the
EPA
Dockets.
Information
claimed
as
CBI
and
other
information
whose
disclosure
is
restricted
by
statute,
which
is
not
included
in
the
official
public
docket,
will
not
be
available
for
public
viewing
in
EPA's
electronic
public
docket.
EPA's
policy
is
that
copyrighted
material
will
not
be
placed
in
EPA's
electronic
public
docket
but
will
be
available
only
in
printed,
paper
form
in
the
official
public
docket.
To
the
extent
feasible,
publicly
available
docket
materials
will
be
made
available
in
EPA's
electronic
public
docket.
When
a
document
is
selected
from
the
index
list
in
EPA
Dockets,
the
system
will
identify
whether
the
document
is
available
for
viewing
in
EPA's
electronic
public
docket.
Although
not
all
docket
materials
may
be
available
electronically,
you
may
still
access
any
of
the
publicly
available
docket
materials
through
the
docket
facility
identified
in
Unit
I.
B.
EPA
intends
to
work
towards
providing
electronic
access
to
all
of
the
publicly
available
docket
materials
through
EPA's
electronic
public
docket.
For
public
commenters,
it
is
important
to
note
that
EPA's
policy
is
that
public
comments,
whether
submitted
electronically
or
in
paper,
will
be
made
available
for
public
viewing
in
EPA's
electronic
public
docket
as
EPA
receives
them
and
without
change,
unless
the
comment
contains
copyrighted
material,
CBI,
or
other
information
whose
disclosure
is
restricted
by
statute.
When
EPA
identifies
a
comment
containing
copyrighted
material,
EPA
will
provide
a
reference
to
that
material
in
the
version
of
the
comment
that
is
placed
in
EPA's
electronic
public
docket.
The
entire
printed
comment,
including
the
copyrighted
material,
will
be
available
in
the
public
docket.
Public
comments
submitted
on
computer
disks
that
are
mailed
or
delivered
to
the
docket
will
be
transferred
to
EPA's
electronic
public
docket.
Public
comments
that
are
mailed
or
delivered
to
the
docket
will
be
scanned
and
placed
in
EPA's
electronic
public
docket.
Where
practical,
physical
objects
will
be
photographed,
and
the
photograph
will
be
placed
in
EPA's
electronic
public
docket
along
with
a
brief
description
written
by
the
docket
staff.

C.
How
and
To
Whom
Do
I
Submit
Comments?
You
may
submit
comments
electronically,
by
mail,
or
through
hand
delivery/
courier.
To
ensure
proper
receipt
by
EPA,
identify
the
appropriate
docket
ID
number
in
the
subject
line
on
the
first
page
of
your
comment.
Please
ensure
that
your
comments
are
submitted
within
the
specified
comment
period.
Comments
received
after
the
close
of
the
comment
period
will
be
marked
``
late.''
EPA
is
not
required
to
consider
these
late
comments.
If
you
wish
to
submit
CBI
or
information
that
is
otherwise
protected
by
statute,
please
follow
the
instructions
in
Unit
I.
D.
Do
not
use
EPA
Dockets
or
e­
mail
to
submit
CBI
or
information
protected
by
statute.
1.
Electronically.
If
you
submit
an
electronic
comment
as
prescribed
in
this
unit,
EPA
recommends
that
you
include
your
name,
mailing
address,
and
an
email
address
or
other
contact
information
in
the
body
of
your
comment.
Also
include
this
contact
information
on
the
outside
of
any
disk
or
CD
ROM
you
submit,
and
in
any
cover
letter
accompanying
the
disk
or
CD
ROM.
This
ensures
that
you
can
be
identified
as
the
submitter
of
the
comment
and
allows
EPA
to
contact
you
in
case
EPA
cannot
read
your
comment
due
to
technical
difficulties
or
needs
further
information
on
the
substance
of
your
comment.
EPA's
policy
is
that
EPA
will
not
edit
your
comment,
and
any
identifying
or
contact
information
provided
in
the
body
of
a
comment
will
be
included
as
part
of
the
comment
that
is
placed
in
the
official
public
docket,
and
made
available
in
EPA's
electronic
public
docket.
If
EPA
cannot
read
your
comment
due
to
technical
difficulties
and
cannot
contact
you
for
clarification,
EPA
may
not
be
able
to
consider
your
comment.
i.
EPA
Dockets.
Your
use
of
EPA's
electronic
public
docket
to
submit
comments
to
EPA
electronically
is
EPA's
preferred
method
for
receiving
comments.
Go
directly
to
EPA
Dockets
at
http://
www.
epa.
gov/
edocket,
and
follow
the
online
instructions
for
submitting
comments.
Once
in
the
system,
select
``
search,''
and
then
key
in
docket
ID
number
OPP
 
2002
 
0283.
The
system
is
an
``
anonymous
access''
system,
which
means
EPA
will
not
know
your
identity,
e­
mail
address,
or
other
contact
information
unless
you
provide
it
in
the
body
of
your
comment.
ii.
E­
mail.
Comments
may
be
sent
by
e­
mail
to
opp­
docket@
epa.
gov,
Attention:
Docket
ID
Number
OPP
 
2002
 
0283.
In
contrast
to
EPA's
electronic
public
docket,
EPA's
e­
mail
system
is
not
an
``
anonymous
access''
system.
If
you
send
an
e­
mail
comment
directly
to
the
docket
without
going
through
EPA's
electronic
public
docket,
EPA's
e­
mail
system
automatically
captures
your
e­
mail
address.
E­
mail
addresses
that
are
automatically
captured
by
EPA's
e­
mail
system
are
included
as
part
of
the
comment
that
is
VerDate
0ct<
31>
2002
19:
49
Dec
23,
2002
Jkt
200001
PO
00000
Frm
00051
Fmt
4703
Sfmt
4703
E:\
FR\
FM\
24DEN1.
SGM
24DEN1
78461
Federal
Register
/
Vol.
67,
No.
247
/
Tuesday,
December
24,
2002
/
Notices
placed
in
the
official
public
docket,
and
made
available
in
EPA's
electronic
public
docket.
iii.
Disk
or
CD
ROM.
You
may
submit
comments
on
a
disk
or
CD
ROM
that
you
mail
to
the
mailing
address
identified
in
Unit
I.
C.
2.
These
electronic
submissions
will
be
accepted
in
WordPerfect
or
ASCII
file
format.
Avoid
the
use
of
special
characters
and
any
form
of
encryption.
2.
By
mail.
Send
your
comments
to:
Public
Information
and
Records
Integrity
Branch
(
PIRIB)
(
7502C),
Office
of
Pesticide
Programs
(
OPP),
Environmental
Protection
Agency,
1200
Pennsylvania
Ave.,
NW.,
Washington,
DC
20460
 
0001,
Attention:
Docket
ID
Number
OPP
 
2002
 
0283.
3.
By
hand
delivery
or
courier.
Deliver
your
comments
to:
Public
Information
and
Records
Integrity
Branch
(
PIRIB),
Office
of
Pesticide
Programs
(
OPP),
Environmental
Protection
Agency,
Rm.
119,
Crystal
Mall
#
2,
1921
Jefferson
Davis
Hwy.,
Arlington,
VA,
Attention:
Docket
ID
Number
OPP
 
2002
 
0283.
Such
deliveries
are
only
accepted
during
the
docket's
normal
hours
of
operation
as
identified
in
Unit
I.
B.
1.

D.
How
Should
I
Submit
CBI
To
the
Agency?

Do
not
submit
information
that
you
consider
to
be
CBI
electronically
through
EPA's
electronic
public
docket
or
by
e­
mail.
You
may
claim
information
that
you
submit
to
EPA
as
CBI
by
marking
any
part
or
all
of
that
information
as
CBI
(
if
you
submit
CBI
on
disk
or
CD
ROM,
mark
the
outside
of
the
disk
or
CD
ROM
as
CBI
and
then
identify
electronically
within
the
disk
or
CD
ROM
the
specific
information
that
is
CBI).
Information
so
marked
will
not
be
disclosed
except
in
accordance
with
procedures
set
forth
in
40
CFR
part
2.
In
addition
to
one
complete
version
of
the
comment
that
includes
any
information
claimed
as
CBI,
a
copy
of
the
comment
that
does
not
contain
the
information
claimed
as
CBI
must
be
submitted
for
inclusion
in
the
public
docket
and
EPA's
electronic
public
docket.
If
you
submit
the
copy
that
does
not
contain
CBI
on
disk
or
CD
ROM,
mark
the
outside
of
the
disk
or
CD
ROM
clearly
that
it
does
not
contain
CBI.
Information
not
marked
as
CBI
will
be
included
in
the
public
docket
and
EPA's
electronic
public
docket
without
prior
notice.
If
you
have
any
questions
about
CBI
or
the
procedures
for
claiming
CBI,
please
consult
the
person
listed
under
FOR
FURTHER
INFORMATION
CONTACT.
E.
What
Should
I
Consider
as
I
Prepare
My
Comments
for
EPA?

You
may
find
the
following
suggestions
helpful
for
preparing
your
comments:
1.
Explain
your
views
as
clearly
as
possible.
2.
Describe
any
assumptions
that
you
used.
3.
Provide
copies
of
any
technical
information
and/
or
data
you
used
that
support
your
views.
4.
If
you
estimate
potential
burden
or
costs,
explain
how
you
arrived
at
the
estimate
that
you
provide.
5.
Provide
specific
examples
to
illustrate
your
concerns.
6.
Make
sure
to
submit
your
comments
by
the
deadline
in
this
notice.
7.
To
ensure
proper
receipt
by
EPA,
be
sure
to
identify
the
docket
ID
number
assigned
to
this
action
in
the
subject
line
on
the
first
page
of
your
response.
You
may
also
provide
the
name,
date,
and
Federal
Register
citation.

II.
What
Action
is
the
Agency
Taking?

EPA
has
received
a
pesticide
petition
as
follows
proposing
the
establishment
and/
or
amendment
of
regulations
for
residues
of
a
certain
pesticide
chemical
in
or
on
various
food
commodities
under
section
408
of
the
Federal
Food,
Drug,
and
Cosmetic
Act
(
FFDCA),
21
U.
S.
C.
346a.
EPA
has
determined
that
this
petition
contains
data
or
information
regarding
the
elements
set
forth
in
FFDCA
section
408(
d)(
2);
however,
EPA
has
not
fully
evaluated
the
sufficiency
of
the
submitted
data
at
this
time
or
whether
the
data
support
granting
of
the
petition.
Additional
data
may
be
needed
before
EPA
rules
on
the
petition.

List
of
Subjects
Environmental
protection,
Agricultural
commodities,
Feed
additives,
Food
additives,
Pesticides
and
pests,
Reporting
and
recordkeeping
requirements.

Dated:
December
10,
2002.
Peter
Caulkins,
Acting
Director,
Registration
Division,
Office
of
Pesticide
Programs.

Summary
of
Petition
The
petitioner
summary
of
the
pesticide
petition
is
printed
below
as
required
by
FFDCA
section
408(
d)(
3).
The
summary
of
the
petition
was
prepared
by
the
petitioner
and
represents
the
view
of
the
petitioner.
The
petition
summary
announces
the
availability
of
a
description
of
the
analytical
methods
available
to
EPA
for
the
detection
and
measurement
of
the
pesticide
chemical
residues
or
an
explanation
of
why
no
such
method
is
needed.

PP
2E6475
EPA
has
received
a
pesticide
petition
(
PP
2E6475)
from
BASF
Corporation:
3000
Continental
Drive
­
North,
Mount
Olive,
NJ
07828
 
1234;
proposing,
pursuant
to
section
408(
d)
of
the
FFDCA,
21
U.
S.
C.
346a(
d),
to
amend
40
CFR
part
180
to
establish
an
exemption
from
the
requirement
of
a
tolerance
for
2­
bromo­
2­
nitro­
1,3­
propanediol
(
Bronopol)
(
CAS
Reg.
No.
52
 
51
 
7)
in
or
on
all
raw
agricultural
commodities
when
used
as
an
in­
can
preservative
in
pesticide
formulations
applied
to
growing
crops,
raw
agricultural
commodities
after
harvest,
and
animals.
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.
Plant
metabolism.
Residue
chemistry
data
are
not
generally
required
by
EPA
regarding
tolerance
exemption
petitions.
Consequently
no
plant
metabolism
data
have
been
generated.
2.
Analytical
method.
Since
this
petition
is
for
an
exemption
from
the
requirement
of
a
tolerance,
an
enforcement
analytical
method
for
2­
bromo­
2­
nitro­
1,
3­
propanediol
is
not
needed.
3.
Magnitude
of
residues.
Based
on
the
proposed
amount
of
2­
bromo­
2­
nitro­
1,3­
propanediol
to
be
used
in
the
final
products
(
0.04%
or
less
by
weight
of
the
total
formulation)
and
the
recommended
frequency
and
rates
of
application
to
growing
crops,
raw
agricultural
commodities
after
harvest,
and
animals,
the
residues
are
expected
to
be
essentially
undetectable
and
not
toxicologically
significant.

B.
Toxicological
Profile
1.
Acute
toxicity.
Bronopol
was
given
as
single
oral
doses
of
200,
280,
390,
550,
or
770
mg/
kg,
as
a
solution
in
distilled
water,
to
groups
of
ten
male
and
ten
female
rats.
The
rats
were
observed
for
a
seven­
day
period.
Overt
signs
of
toxicity
were
seen
immediately
after
dosing
with
280
mg/
kg
or
more,
and
within
1
hour
in
males
given
200
mg/
kg.
The
signs
included
sedation,
wheezing,
gasping,
nasal
exudate,
cyanosis,
increased
salivation
and
ataxia.
Animals
given
550
or
770
mg/
kg
VerDate
0ct<
31>
2002
19:
49
Dec
23,
2002
Jkt
200001
PO
00000
Frm
00052
Fmt
4703
Sfmt
4703
E:\
FR\
FM\
24DEN1.
SGM
24DEN1
78462
Federal
Register
/
Vol.
67,
No.
247
/
Tuesday,
December
24,
2002
/
Notices
also
had
slow
or
labored
respiration,
and
two
females
became
prostrate.
Most
deaths
occurred
within
19
hours
after
dosing,
but
some
occurred
up
to
72
hours.
There
were
no
gross
abnormalities
at
autopsy
of
the
decedents
or
in
animals
killed
at
the
end
of
the
study.
The
LD50
in
male
rats
was
307
mg/
kg
and
in
female
rats
was
342
mg/
kg.
In
a
further
oral
study
groups
of
ten
male
rats
were
given
single
doses
of
Bronopol
at
36,
54,
80,
120,
270,
400,
or
600
mg/
kg,
as
a
suspension
in
0.4%
aqueous
Cellosize
solution.
The
rats
were
observed
for
up
to
ten
days
after
treatment.
Overt
signs
of
toxicity
were
seen
within
30
minutes
after
dosing
with
80
mg/
kg
or
more,
and
included
wheezing,
gasping
or
labored
respiration
and
nasal
exudate.
Animals
in
the
higher
dose
groups
were
inactive
and
adopted
a
low
or
hunched
body
position.
Deaths
occurred
in
these
groups
up
to
five
days
after
treatment;
macroscopic
findings
in
the
decedents
included
evidence
of
gastrointestinal
irritation
at
120
mg/
kg
or
more,
enlarged
and
dark
red
adrenals
in
some
animals
given
400
or
600
mg/
kg,
small
spleens
in
a
few
rats
given
80
or
120
mg/
kg,
and
pale
areas
on
the
livers
at
600
mg/
kg.
At
terminal
autopsy,
one
animal
given
400
mg/
kg
also
had
a
small
spleen.
Statistical
analysis
of
the
mortality
data
indicated
that
the
LD50
was
254
mg/
kg.
In
an
acute
inhalation
study
a
group
of
six
rats
and
two
groups
of
eight
rats
were
exposed
for
6­
hour
periods
to
Bronopol
dust
at
nominal
concentrations
of
5,
0.5,
or
0.05
mg
per
liter
air
respectively.
The
animals
were
then
kept
under
observation
for
up
to
14
days.
Exposure
of
rats
to
5
mg
dust
per
liter
air
caused
severe
eye
irritation,
dyspnea
and
loss
of
bodyweight.
Exposure
to
0.5
mg
dust
per
liter
air
caused
only
slight
eye
irritation
and
mild
dyspnea,
while
no
definite
signs
of
irritation
were
observed
in
animals
exposed
to
0.05
mg
dust
per
air.
In
a
second
inhalation
study
four
groups
of
10
rats
(
5
males
and
5
females)
were
exposed
to
Bronopol
at
0
(
filtered
air
negative
control),
0.038,
0.089
or
0.588
mg/
by
inhalation
(
nose­
only)
over
a
period
of
4
hours.
Exposure
was
followed
by
an
observation
period
of
14
days.
In
the
high
dose
group
one
animal
died
overnight
after
exposure,
and
2
more
animals
were
killed
during
the
following
day
because
of
severe
eye
inflammation.
Signs
of
marked
irritancy
were
recorded
in
high
dose
animals
but
disappeared
by
the
third
observation
day.
Minor
treatment­
related
signs
(
piloerection
and
hunched
posture)
were
observed
on
the
day
of
treatment
in
some
intermediate
dose
rats.
There
was
no
effect
in
the
low
dose
group.
There
were
no
treatment­
related
effects
on
body
weight
or
treatment­
related
pathological
findings
except
for
local
dermatitis
and
ulceration
in
2
high
dose
animals
possibly
attributable
to
dermal
exposure
to
the
test
article.
Several
studies
as
summarized
below
determined
2­
bromo­
2­
nitro­
1,3­
propanediol
to
be
irritant
to
the
eye.
Bronopol
in
polyethylene
glycol
300
 
0.1
ml
volumes
of
0.5
or
2%
Bronopol
in
polyethylene
glycol
300
were
instilled
into
one
eye
of
each
of
six
rabbits,
three
rabbits
per
concentration.
The
other
eye
in
each
case
was
treated
with
solvent
only.
The
2%
solution
was
instilled
only
once,
whereas
the
0.5%
solution
was
instilled
on
four
successive
days.
The
2%
solution
of
Bronopol
in
polyethylene
glycol
300,
instilled
once,
caused
moderate
inflammation
and
slight
conjunctival
edema
which
subsided
after
5
hours.
The
0.5%
solution,
instilled
on
four
successive
days,
had
effects
similar
to
those
produced
by
the
solvent
alone.
Bronopol
in
saline
­
Two
drops
of
a
solution
containing
0.5%
w/
v
Bronopol
in
normal
saline
were
applied
to
one
eye
of
three
New
Zealand
White
rabbits
once
daily
on
four
successive
days.
The
other
eye
(
control)
of
each
rabbit
was
treated
with
normal
saline.
The
eyes
were
examined
for
irritation
at
15
and
30
minutes,
and
at
1,
2,
3,
4,
and
24
hours
after
treatment
each
day.
One
rabbit
developed
moderate
inflammation
and
very
slight
edema
of
the
conjunctiva
between
two
and
four
hours
after
the
first
application,
but
this
subsided
within
24
hours.
No
other
reactions
were
observed.
Bronopol
in
polyethylene
glycol
400
­
One
drop
of
Bronopol
at
0
(
vehicle
control),
0.5,
2,
or
5%
in
polyethylene
glycol
400
was
added
to
one
eye
of
12
rabbits,
3
animals
per
test
concentration.
The
other
eye
of
each
rabbit
was
left
untreated.
After
24
hours
the
eyes
were
irrigated
with
300
ml
of
lukewarm
water.
Ocular
reactions
were
assessed
according
to
the
FDA
method
at
1,
24,
48,
and
72
hours,
and
then
7,
14,
and
21
days
after
treatment.
Immediately
after
treatment,
with
all
the
solutions,
most
rabbits
exhibited
head
shaking
and
blinking
and/
or
rubbing
the
treated
eye.
After
1
hour
all
the
animals
developed
conjunctival
reactions
which
had
largely
subsided
by
24
hours,
except
in
the
most
severely
affected
cases.
One
rabbit
treated
with
5%
Bronopol
had
conjunctival
reactions
that
persisted
for
72
hours.
The
lower
concentrations
produced
less
severe
and
less
persistent
conjunctival
reactions,
and
none
of
the
concentrations
elicited
reactions
in
the
cornea
or
iris.
It
was
concluded
that
Bronopol
in
polyethylene
glycol
400
was
irritant
at
5%
but
not
at
2
or
0.5%,
when
instilled
once
only
into
the
eye
of
the
New
Zealand
White
rabbit.
Bronopol
is
also
irritant
to
the
skin.
In
a
cumulative
irritancy
study
dilutions
of
Bronopol
at
0
(
vehicle
control),
0.1,
0.5,
1,
2.5,
and
5%
in
petrolatum
was
applied
daily
for
21
days
to
the
same
site
on
the
back
of
8
men.
The
treatment
sites
were
occluded.
Readings
were
made
daily
on
a
scale
of
0
to
4.
The
skin
irritancy
threshold
concentration
of
Bronopol
was
approximately
0.5
to
1.0%.
To
determine
if
the
subjects
had
been
sensitized,
they
were
further
elicited
after
a
10­
day
rest
period.
Two
subjects
reacted
at
0.5
and
1%
Bronopol.
One
reacted
at
0.1%.
These
men
received
a
product
use
test
consisting
of
applications
(
without
patching)
to
the
cubital
fossa
twice
daily
for
7
days.
These
were
negative.
In
a
single,
4
hour,
semi­
occluded
dermal
application
of
undiluted
Bronopol
to
the
skin
of
six
rabbits
produced
severe
dermal
reactions,
including
eschar
formation,
necrosis
and
severe
edema.
Other
adverse
dermal
reactions
noted
were
slight
hemorrhage
of
the
dermal
capillaries,
blanching
or
brown
discoloration
of
the
skin,
desquamation
and
scar
tissue.
The
absence
of
fur
growth
was
also
occasionally
noted
on
day
fourteen
with
further
effects
indicative
of
corrosion.
A
primary
irritation
index
of
6.2
was
produced
and
evidence
of
corrosive
effects
were
noted
fourteen
days
after
treatment.
Undiluted
Bronopol
was
found
to
be
a
severe
irritant/
corrosive
to
rabbit
skin.
An
acute
rabbit
dermal
toxicity
study
gave
a
dermal
LD50
of
>
2,000
mg/
kg
body
weight.
The
study
was
based
on
the
EEC,
OECD
and
EPA/
OPPTS
guidelines.
A
single
oral
dose
of
2,000
mg/
kg
body
weight
of
the
test
material
preparation
in
0.5%
Tylose
was
applied
in
a
group
of
ten
rats
(
five
males
and
five
females)
to
the
clipped
epidermis
(
dorsal
and
dorsolateral
parts
of
the
trunk)
and
covered
by
a
semi
occlusive
dressing
for
24
hours.
No
mortality
occurred.
Signs
of
toxicity
noted
in
the
2,000
mg/
kg
groups
comprised
poor
general
state,
dyspnea
and
apathy.
Findings
were
observed
until
including
study
day
1.
The
following
skin
effects
were
observed
at
the
application
site:
white
discoloration,
erythema,
edema,
eczematoid
skin
change,
scaling,
and
crust
formation.
Findings
were
observed
until
termination
of
the
study.
The
animals
did
not
gain
weight
during
the
first
post
exposure
observation
week
but
restarted
to
gain
weight
thereafter.
No
abnormalities
were
noted
in
the
animals
necropsied
at
the
end
of
the
study,

VerDate
0ct<
31>
2002
19:
49
Dec
23,
2002
Jkt
200001
PO
00000
Frm
00053
Fmt
4703
Sfmt
4703
E:\
FR\
FM\
24DEN1.
SGM
24DEN1
78463
Federal
Register
/
Vol.
67,
No.
247
/
Tuesday,
December
24,
2002
/
Notices
except
in
the
skin
of
the
application
site,
where
incrustation
and
full
thickness
necrosis
(
9/
10
animals)
was
observed.
Under
the
conditions
of
this
study,
the
acute
dermal
median
lethal
dose
(
LD50)
of
the
test
substance
was
found
to
be
greater
than
2000
mg/
kg
body
weight
for
male
and
female
animals.
2­
bromo­
2­
nitro­
1,3­
propanediol
is
classed
as
a
weak
skin
sensitizer
as
indicated
in
four
Magnusson
and
Kligman
guinea
pig
skin
sensitization
studies
as
summarized
below.
Study
1
­
The
test
method
was
the
Magnusson
and
Kligman
guinea
pig
maximization
test,
but
using
10
test
animals,
4
treated
controls
and
4
untreated
controls.
Induction
in
the
test
animals
was
by
intradermal
injections
of
0.03%
w/
v
Bronopol
in
saline
and
Complete
Freunds
Adjuvant
in
the
shoulder
region.
The
induction
process
was
supplemented
7
days
later
by
1.5%
w/
v
Bronopol
in
distilled
water
applied
under
occlusion
to
the
injection
sites.
Fourteen
days
later
the
animals
were
challenged
on
the
shaved
flank
by
occluded
patch
with
0.4%
w/
v
Bronopol
in
distilled
water.
Twentyfour
hours
after
the
challenge
the
patch
was
removed
and
the
reaction
site
examined
24
and
48
hours
after
removal.
A
further
3
challenges
were
made
at
either
1
or
2
week
intervals.
The
treated
controls
were
4
guinea
pigs
treated
the
same
as
the
test
animals
except
that
the
test
substance
was
omitted
from
the
intradermal
injection
and
the
covered
patch
induction
procedures.
At
each
challenge
4
previously
untreated
animals
were
challenged
as
per
the
test
animals.
This
group
formed
the
untreated
control.
In
the
Magnusson
and
Kligman
Maximization
test,
sensitization
is
normally
assessed
after
one
challenge.
At
this
stage
in
this
test
there
was
no
sensitization.
One
animal
was
sensitized
after
2
challenges
and
a
further
animal
after
3
challenges.
In
this
test
2/
10
animals
sensitized
after
one
challenge
is
classified
as
a
mild
sensitizer
(
Grade
II),
but
since
3
challenges
were
necessary
before
2/
10
animals
were
sensitized,
the
sensitization
potential
must
be
regarded
as
less
than
mild,
hence
Bronopol
was
found
to
be
a
weak
sensitizer
by
this
method.
Study
2
­
Induction
was
carried
out
as
in
Study
1
except
that
9
guinea
pigs
were
used;
induction
was
0.02%
Bronopol
in
saline
and
induction
supplementation
was
6
 
7
days
later
with
5%
Bronopol
in
saline.
Fourteen
days
later
the
animals
were
challenged
(
24
hour
occluded
patch)
with
1%
Bronopol
in
saline.
One
week
later
the
animals
were
subjected
to
a
crossreaction
challenge
with
2%
formalin.
Further
challenges
were
made
with
Bronopol
and
formalin
after
2
and
3
weeks.
Any
challenge
reactions
were
recorded
after
24
and
48
hours.
2/
9
animals
showed
sensitization
reactions
to
Bronopol
at
challenge
1.
Animals
were
not
challenged
with
Bronopol
at
challenge
2.
No
sensitization
reactions
were
seen
at
challenge
3
and
1/
9
animals
showed
an
equivocal
reaction
at
challenge
4.
1/
9
animals
showed
an
equivocal
reaction
to
formalin
at
challenge
2,
but
there
was
no
evidence
of
cross­
reaction
at
challenges
3
and
4.
It
was
concluded
that
Bronopol
was
a
weak
sensitizer
under
the
conditions
of
this
test.
There
was
no
significant
evidence
of
cross­
reaction
to
challenge
with
formalin.
Study
3
­
Induction
was
carried
out
as
in
Study
1
except
that
9
guinea
pigs
were
used;
induction
was
0.02%
Bronopol
in
saline
and
induction
supplementation
was
6
 
7
days
later
with
2.5%
Bronopol
in
saline.
Fourteen
days
later
the
animals
were
challenged
(
24
hour
occluded
patch)
with
0.25%
Bronopol
in
saline;
a
second
challenge
was
made
after
a
further
7
days.
Any
challenge
reactions
were
recorded
after
24
and
48
hours.
There
was
no
evidence
of
sensitization
in
the
9
animals
tested
at
either
challenge,
and
it
was
concluded
that
Bronopol
was
not
a
sensitizer
under
the
conditions
of
this
test.
Study
4
­
Induction
was
carried
out
as
in
Study
1
except
that
induction
was
0.02%
Myacide
BT
(
a
minimum
of
98%
Bronopol)
in
saline
and
induction
supplementation
was
6
 
7
days
later
with
2.5%
Myacide
BT
in
saline.
Fourteen
days
later
the
animals
were
challenged
(
24
hour
occluded
patch)
with
0.25%
Myacide
BT
in
saline;
a
second
challenge
was
made
after
a
further
7
days.
Any
challenge
reactions
were
recorded
after
24
and
48
hours.
There
was
no
evidence
of
sensitization
in
the
10
animals
tested
at
either
challenge,
and
it
was
concluded
that
Myacide
BT
was
not
a
sensitizer
under
the
conditions
of
this
test.
The
overall
conclusion
was
that
Bronopol
has
a
very
low,
and
variable,
sensitization
potential
in
the
stringent
Magnusson
and
Kligman
guinea
pig
maximization
test
and
is
at
most
a
weak
sensitizer
in
this
species.
There
was
no
evidence
that
the
animals
had
become
sensitized
to
formalin.
2.
Genotoxicty.
Mutagenicity
studies
including
in
vitro/
in
vivo
in
mouse
erythrocytes
(
micronucleus
assay),
chromosomal
aberration
test
in
human
lymphocytes,
Salmonella
typhimurium
plate
(
Ames)
tests
with
and
without
activation
were
negative.
Bronopol
did
not
induce
mutations
in
the
in
vitro
bacterial
mutagenicity
assay
(
TX
86004)
or
the
V79
cell
mutation
assay
(
TX
86043),
neither
was
there
evidence
of
activity
in
assays
for
host­
mediated
bacterial
mutagenicity
or
dominant
lethality
conducted
in
mice
TX
74034).
Furthermore,
there
was
no
increase
in
the
incidence
of
micronuclei
in
polychromatic
erythrocytes
of
bone
marrow
from
male
and
female
mice,
24,
48,
or
72
hours
after
administration
of
single
oral
doses
up
to
a
maximum
tolerated
level
of
160
mg/
kg
(
TX
86001).
However,
weak
in
vitro
clastogenic
activity
was
detected
in
cultured
human
lymphocytes
exposed
for
24
hours,
in
the
absence
of
S
 
9,
to
Bronopol
at
30
µ
g/
ml
(
TX
86049).
Bronopol
is
normally
self­
stabilizing
at
about
pH
4
in
aqueous
media,
but
decomposes
at
elevated
temperature
and
more
alkaline
pH
to
release
formaldehyde
as
a
breakdown
product.
Under
the
conditions
of
the
human
lymphocyte
chromosome
assay,
only
about
10%
of
an
initial
30
µ
g/
ml
concentration
of
Bronopol
in
the
culture
medium
(
pH
6.9)
could
be
detected
by
analysis
after
2
hours
incubation
at
370
C
(
DT
86029),
and
a
formaldehyde
concentration
of
4.2
µ
g/
ml
was
found
at
this
time
(
DT
86030);
the
calculated
value
for
formaldehyde
released
from
complete
breakdown
of
the
30
µ
g/
ml
concentration
of
Bronopol
is
4.5
µ
g/
ml.
Formaldehyde
shows
clastogenic
properties
in
vitro
that
include
the
induction
of
chromosome
aberrations
in
human
lymphocytes.
Furthermore,
in
a
lymphocyte
assay
conducted
in­
house
(
TX
86050),
formaldehyde,
in
the
absence
of
S
 
9
activation,
elicited
chromosome
damage
that
was
qualitatively
and
quantitatively
similar
to
that
seen
in
the
assay
of
Bronopol.
These
findings,
supported
by
the
analytical
data,
indicate
that
the
in
vitro
clastogenicity
seen
with
Bronopol
is
due
to
its
breakdown
to
formaldehyde.
Although
formaldehyde
is
a
clastogen
in
vitro,
its
reactivity
precludes
distribution
in
vivo,
so
it
is
inactive
in
bone
marrow
and
germ
cells.
The
relative
instability
of
Bronopol,
like
that
of
other
non­
carcinogenic
formaldehyde­
releasing
agents,
does
not
allow
it
to
transport
formaldehyde
to
these
sites.
In
contrast,
the
carcinogen,
hexamethylphosphoramide
(
HMPA),
is
more
stable
and
requires
metabolic
activation
to
release
formaldehyde;
as
a
result,
HMPA
is
clastogenic
in
bone
marrow
and
has
adverse
effects
in
germ
cells.
In
conclusion,
the
testing
of
Bronopol
over
a
wide
range
of
genetic
endpoints
has
revealed
only
a
single
adverse
finding,
namely
weak
in
vitro
clastogenicity,
and
this
result
is
clearly
VerDate
0ct<
31>
2002
19:
49
Dec
23,
2002
Jkt
200001
PO
00000
Frm
00054
Fmt
4703
Sfmt
4703
E:\
FR\
FM\
24DEN1.
SGM
24DEN1
78464
Federal
Register
/
Vol.
67,
No.
247
/
Tuesday,
December
24,
2002
/
Notices
attributable
to
the
release
of
formaldehyde
from
Bronopol
under
the
conditions
of
the
lymphocyte
assay.
The
consensus
of
negative
findings
in
shortterm
in
vitro
tests,
together
with
the
negative
finding
in
an
in
vivo
test
for
chromosome
damage
and
the
absence
of
oncogenicity
in
the
life
span
studies
in
rats
and
mice
(
see
below),
indicates
that
Bronopol
does
not
present
a
genotoxic
hazard.
In
a
2­
year
rat
(
drinking
water)
chronic
toxicity
and
tumorgenicity,
Bronopol
dissolved
in
tap
water
was
dosed
to
28
day
old
rats
in
4
groups
(
45
male
and
45
female
in
the
main
groups
and
15
male
and
15
female
in
the
satellite
groups)
via
the
drinking
water
for
104
weeks
at
0
(
untreated
control),
10,
40,
and
160
mg/
kg/
day.
The
main
groups
were
reserved
for
evaluation
of
tumorigenic
potential
and
were
not
used
for
blood
and
urine
samples
during
the
study;
the
satellite
groups
were
used
for
blood
and
urine
samples
during
the
study
and
were
not
included
in
the
tumorigenicity
assessment.
The
results
at
the
various
dose
levels
may
be
summarized
as
follows:
160
mg/
kg/
day
 
Reduced
grooming
activity
during
the
final
year
of
treatment.
 
Significantly
increased
mortality.
 
Reduced
weight
gain
from
week
3
onwards
among
males
and
from
week
7
onwards
among
females.
 
Lower
food
intake
among
males
from
week
13
onwards.
 
Marked
reduction
in
water
intake
throughout
the
dosing
period
and
an
associated
reduction
in
urine
volume
noted
at
weeks
25,
52,
and
103.
 
Increase
incidence
of
progressive
glomerulonephrosis
in
males
and
females.
 
At
week
52,
urine
repeatedly
positive
for
hemoglobin
in
4/
10
males
and
1/
10
females,
at
week
77
in
4/
10
males
and
3/
10
females,
and
at
week
103
in
10/
10
males
and
1/
10
females.
 
Stomach
lesions
in
20
males
and
15
females
and
the
gastric
lymph
nodes
showed
dilation
of
the
sinusoids
in
4
males
and
5
females.
 
Squamous
metaplasia,
inflammation
or
atrophic
acini
in
the
salivary
glands
of
12
males
and
11
females.
40
mg/
kg/
day
 
Reduced
weight
gain
from
weeks
27
to
78
among
males.
 
Lower
food
intake
from
weeks
53
to
78
among
males.
 
Moderate
reduction
in
water
intake
throughout
the
dosing
period.
 
At
week
77,
urine
repeatedly
positive
for
hemoglobin
in
6/
10
males
and
at
week
103
in
3/
10
males.
 
Stomach
lesion
in
1
male.
 
Squamous
metaplasia,
inflammation
or
atrophic
acini
in
the
salivary
glands
of
12
males
and
2
females.
10
mg/
kg/
day
 
Small
but
definite
reduction
in
water
intake
throughout
the
dosing
period.
 
At
week
77,
urine
repeatedly
positive
for
hemoglobin
in
2/
10
males
and
at
week
103
in
2/
9
males.
 
Stomach
lesions
in
1
male
and
1
female.
 
Squamous
metaplasia
and/
or
inflammation
or
atrophic
acini
in
the
salivary
glands
of
5
males
and
1
female.
Control
 
At
week
52,
urine
repeatedly
positive
for
hemoglobin
in
1/
10
males
and
0/
10
females,
at
week
77
in
2/
10
males
and
0/
10
females,
and
at
week
103
in
3/
10
males
and
1/
10
females.
 
Stomach
lesions
in
1
male
and
2
females.
 
Squamous
metaplasia
and/
or
inflammation
or
atrophic
acini
in
the
salivary
glands
of
3
males
and
2
females.
The
evidence
of
toxic
effects
related
to
the
administration
of
Bronopol
was
a
reduction
in
food
intake,
impaired
food
utilization
efficiency
associated
with
reduced
bodyweight
gain,
and
increased
mortality.
Changes
in
the
stomach
and
gastric
lymph
nodes
were
attributed
to
the
irritant
effect
of
Bronopol.
Unpalatability
reduced
the
water
intake
and
was
associated
with
a
reduced
output
of
urine,
an
increased
incidence
of
hemoglobinuria
and
an
exacerbation
of
the
spontaneous
incidence
of
progressive
glomerulonephrosis.
Treatment
with
Bronopol
exacerbated
a
spontaneous
change
in
the
salivary
glands.
These
effects
were
dose
related
and
apart
from
a
small
effect
on
water
intake
that
was
related
to
palatability,
there
was
no
evidence
of
toxicity
at
10
mg/
kg/
day.
There
was
no
evidence
to
suggest
that
the
administration
of
Bronopol
affected
the
tumor
incidence.
In
summary,
the
study
gave
a
systemic
no
observed
adverse
effect
level
(
NOAEL)
of
10
mg/
kg/
day,
a
lowest
effect
level
(
LEL)
of
40
mg/
kg/
day
and
found
2­
bromo­
2­
nitro­
1,3­
propanediol
(
Bronopol)
to
be
not
carcinogenic.
3.
Reproductive
and
developmental
toxicity.
In
a
two­
generation
reproduction
study
in
rats
Bronopol
was
administered
to
rats
in
the
drinking
water
at
concentrations
of
25,
70,
or
200
mg/
kg/
day.
Thirteen
males
and
26
females
were
treated
for
a
minimum
of
80
days
prior
to
mating.
They
were
mated
on
two
separate
occasions
to
produce
the
F1a
and
F1b
litters.
Weanlings
from
the
F1b
litters
were
randomly
selected
(
13
males
and
26
females)
to
become
parents
of
the
next
generation.
The
F1
parents
were
treated
for
a
minimum
of
87
days
prior
to
mating,
and
were
mated
on
two
separate
occasions
to
produce
the
F2a
and
F2b
litters.
In
the
F0
generation,
one
female
from
each
of
the
control
and
low­
dose
groups,
and
one
male
and
five
females
from
the
high­
dose
group
died
or
were
sacrificed
in
extremis
during
the
study;
in
the
F1
generation,
one
female
from
each
of
the
low­,
mid­
and
high­
dose
groups
died
before
the
end
of
the
study.
There
were
no
treatment­
related
aspects,
so
these
deaths
were
considered
to
have
been
incidental
to
Bronopol.
Food
consumption
for
the
high­
dose
group
was
consistently
lower
than
controls
for
the
F0
males,
for
F0
females
during
the
initial
two
weeks
of
treatment
and
the
lactation
periods
for
both
mates,
and
for
F1
females
during
the
lactation
period
of
the
F2a
mate.
Water
consumption
was
reduced
in
all
treated
groups,
in
a
dose­
related
manner,
throughout
most
of
the
study;
this
contributed
to
the
lower
achieved
dosages
of
Bronopol
that
animals
received,
namely
22.55,
55.2,
or
147
mg/
kg.
The
female
fertility
index
for
the
high­
dose
group
was
slightly
lower
than
control
at
the
F1
mate
only.
Mean
body
weights
of
the
offspring
of
the
F0
and
F1
high­
dose
parents
(
F1a
and
F1b,
and
F2a
and
F2b,
respectively)
were
lower
than
the
control
throughout
the
lactation
periods.
Mean
body
weights
of
the
F1b
pups
from
the
low­
and
middose
groups
were
slightly
lower
than
control
on
day
21
of
the
lactation
period.
There
were
no
other
test
articlerelated
macroscopic
or
microscopic
changes.
There
was
a
dose­
related
increase
in
the
kidney
weights
of
treated
F0
females,
though
the
difference
between
the
low
dose
group
and
controls
was
minimal.
In
the
high­
dose
group
animals
there
was
a
decrease
in
the
absolute
weights
of
the
livers,
and
possibly
also
the
hearts,
of
F1
males,
and
in
the
absolute
liver
weights
of
F2b
males
and
females;
these
females
also
had
lower
absolute
kidney
weights.
In
conclusion,
ingestion
of
Bronopol
elicited
signs
of
toxicity
at
all
dosages,
though
the
only
reproductive
or
litter
parameter
affected
at
the
25
and
70
mg/
kg/
day
dosages
was
body
weight
of
F1b
pups
at
weaning,
where
a
minimal
decrease
was
seen.
An
early
rat
dermal
developmental
toxicity
study
gave
a
maternal
NOAEL
>
40
mg/
kg/
day
(
HDT)
considering
2­
bromo­
2­
nitro­
1,3­
propanediol
as
a
severe
dermal
irritant
in
rats.
Further
development
toxicity
studies
have
been
carried
out
for
both
the
rat
and
the
rabbit.
In
the
rat
study
three
groups
of
24
timed­
mated
female
rats
were
dosed
once
daily,
orally
by
gavage,
with
VerDate
0ct<
31>
2002
19:
49
Dec
23,
2002
Jkt
200001
PO
00000
Frm
00055
Fmt
4703
Sfmt
4703
E:\
FR\
FM\
24DEN1.
SGM
24DEN1
78465
Federal
Register
/
Vol.
67,
No.
247
/
Tuesday,
December
24,
2002
/
Notices
solutions
of
Bronopol
at
dose
levels
of
10,
28,
or
80
mg/
kg/
day
from
days
6
to
15
of
pregnancy,
inclusive.
A
similar
group
of
females
were
dosed
with
the
vehicle
(
purified
water
acidified
to
pH
4)
by
the
same
route
and
over
the
same
period,
and
served
as
controls.
Maternal
clinical
signs,
bodyweights
and
food
consumption
were
recorded.
On
day
20
of
pregnancy,
the
females
were
killed
and
a
necropsy
was
performed.
Numbers
of
corpora
lutea
and
live
and
dead
implantations
were
recorded.
Live
fetuses
were
weighed,
sexed
and
examined
for
external
and
visceral
abnormalities.
Two
thirds
of
the
fetuses
were
also
examined
for
skeletal
abnormalities.
There
was
evidence
of
maternal
toxicity
following
oral
gavage
administration
of
Bronopol
at
80
mg/
kg/
day,
characterized
by
retarded
bodyweight
gain
over
days
6
to
7
of
pregnancy.
There
was
no
evidence
of
maternal
toxicity
at
either
10
or
28
mg/
kg/
day.
There
was
no
evidence
of
developmental
toxicity
at
any
of
the
dose
levels
investigated.
There
may
be
an
association
of
treatment
at
80
mg/
kg/
day
with
advanced
ossification
of
sacral
arches
and
at
28
and
80
mg/
kg/
day
with
advanced
ossification
of
the
forelimb
phalanges.
However,
neither
of
these
findings
in
these
groups
was
unusually
advanced
when
compared
to
historical
background
data.
In
a
second
study
using
rabbit
groups
of
18,
19,
or
20
timed­
mated
female
animals
were
dosed
daily
between
7
and
19
days
of
pregnancy,
inclusive,
by
the
oral
route
with
aqueous
solutions
of
Bronopol
at
dose
levels
of
0
(
control),
5,
20,
40,
and
80
mg/
kg/
day.
Day
0
of
pregnancy
was
the
day
of
mating.
80
mg/
kg/
day
was
selected
as
a
level
which
should
elicit
maternal
effects.
However,
in
the
event
that
the
effects
may
have
been
too
severe,
40
mg/
kg/
day
was
selected
as
the
next
highest
level
known
to
be
tolerated
by
the
pregnant
rabbit.
The
lower
dose
level
of
5
mg/
kg/
day
and
the
intermediate
dose
level
of
20
mg/
kg/
day
were
expected
to
be
`
no
effect'
levels.
Maternal
clinical
condition,
bodyweight,
and
food
consumption
were
recorded.
The
females
were
killed
on
day
28
of
pregnancy
and
a
necropsy
was
performed.
They
were
weighed,
sexed
and
examined
for
external,
visceral,
and
skeletal
abnormalities.
At
80
mg/
kg/
day,
Bronopol
elicited
severe
maternal
toxicity
at
the
onset
of
dosing.
The
animals
recovered
after
dosing
ceased,
but
the
outcome
of
pregnancy
was
affected.
There
was
embryotoxicity
characterized
by
growth
retardation
and
a
slightly
higher
than
expected
incidence
of
fetal
abnormalities.
This
embryotoxicity
was
considered
likely
to
be
related
to
the
maternal
toxicity.
At
40
mg/
kg/
day,
which
was
considered
to
be
the
highest
level
likely
to
be
tolerated
by
the
pregnant
rabbit
without
eliciting
severe
maternal
toxicity,
there
was
no
evidence
of
adverse
effects
of
treatment
on
the
pregnant
rabbit
or
developing
embryos.
This
dose
level
was
therefore
considered
to
be
the
`
no
effect'
level
of
Bronopol
with
regard
to
developmental
toxicity.
4.
Subchronic
toxicity.
A
13­
week
rat
gavage
study
showed
a
NOAEL
of
20
mg/
kg/
day
and
a
lowest
observed
adverse
effect
level
(
LOAEL)
of
80
mg/
kg/
day.
Bronopol
as
a
solution
in
distilled
water
was
dosed
to
CD
rats
(
4
groups
of
20
males
and
20
females)
by
oral
gavage
once
per
day,
seven
days
per
week
for
13
weeks
at
0
(
untreated
control),
20,
80,
and
160
mg/
kg/
day.
Reaction
to
treatment
was
as
follows:
160
mg/
kg/
day
­
Severe
respiratory
distress
and
abdominal
distension;
reduced
bodyweight
gain
and
food
consumption;
death
of
22
males
and
14
females
(
includes
4
male
and
3
female
rats
which
replaced
rats
dying
after
one
dose);
all
surviving
rats
were
killed
on
day
9;
autopsy
showed
gaseous
and
fluid
distension
of
the
gastro­
intestinal
tract
in
the
majority
of
decedents;
ulceration,
epithelial
hyperplasia
and
hyperkeratosis
or
congested
vessels
in
the
stomachs
of
2
males
and
4
females.
80
mg/
kg/
day
­
Severe
respiratory
distress
and
abdominal
distension,
the
latter
sign
confined
to
6
males
and
6
females
which
subsequently
died.
At
week
6,
only
4
males
and
2
females
showed
slight
respiratory
difficulty.
Seven
males
and
9
females
died
with
autopsy
showing
gaseous
and
fluid
distension
of
the
gastro­
intestinal
tract;
reduced
bodyweight
gain
and
food
consumption
for
the
first
week
of
treatment
only;
renal
changes
in
2
males.
20
mg/
kg/
day
­
In
one
male,
respiratory
distress,
which
subsequently
regressed;
renal
changes
in
2
males.
A
13­
week
dog
gavage
study
showed
a
NOAEL
of
8
mg/
kg/
day
and
LOAEL
of
20
mg/
kg/
day.
Bronopol
dissolved
in
water
was
dosed
to
Beagle
dogs
(
4
groups
of
3
males
and
3
females)
by
oral
gavage
once
per
day,
seven
days
per
week
for
3
months
(
13
weeks)
at
0
(
untreated
control),
4,
8,
and
20
mg/
kg/
day.
One
pair
of
dogs
was
dosed
at
levels
of
20
 
40
mg/
kg/
day,
over
a
period
of
2
weeks
in
order
to
determine
the
vomiting
threshold
of
Bronopol.
This
was
found
to
be
at
a
dosage
of
approximately
20
mg/
kg/
day.
During
the
study
vomiting
occurred
within
30
minutes
of
dosing
and
no
other
clinical
signs
were
observed.
Macroscopic
post
mortem
examination
revealed
no
abnormalities.
In
the
main
study
there
were
no
deaths.
Vomiting,
mainly
at
20
mg/
kg/
day,
within
0.5
hour
of
dosing
was
observed
with
occasional
passage
of
liquid
feces
and
red­
stained
mucus
in
isolated
animals,
both
dosed
and
control.
There
were
no
adverse
effects
on
food
or
water
consumption,
or
on
bodyweight.
There
were
no
abnormalities
of
the
eye;
no
macroscopic
post
mortem
abnormalities;
or
morphological
changes
or
variations
from
normal
in
histological
tissue
examination
which
could
be
related
to
dosage
of
the
test
compound.
After
dosing
for
6
weeks,
one
animal
receiving
8
mg/
kg/
day
had
a
serum
alkaline
phosphatase
value
approximating
to
the
upper
limit
of
normality
of
35
King
Armstrong
units;
after
12
weeks,
however,
the
value
was
well
within
normal
limits.
After
dosing
for
12
weeks
the
group
mean
total
white
cell
count,
although
within
normal
limits,
was
significantly
lower
in
dogs
receiving
8
and
20
mg/
kg/
day
than
in
the
controls.
One
animal
receiving
4
mg/
kg/
day
had
a
serum
glutamicpyruvic
transaminase
value
after
12
weeks
which
exceeded
the
upper
limit
of
normality
of
50
mU/
ml.
Apart
from
the
liver
of
one
dog
receiving
20
mg/
kg/
day
which
was
heavier
than
would
normally
be
expected,
all
organ
weights
were
within
normal
limits.
However,
when
expressed
as
a
percentage
of
bodyweight
the
mean
liver
and
spleen
weights
for
dogs
receiving
20
mg/
kg/
day
were
significantly
heavier
than
the
control
values.
5.
Chronic
toxicity.
A
2­
year
toxicity/
carcinogenicity
Bronopol
study
(
administration
via
drinking
water)
in
rats
showed
a
NOAEL
of
 
7
mg/
kg/
day
and
a
LEL
of
<
32
mg/
kg/
day.
For
more
detail
see
the
carcinogenicity
summary
in
Unit
B.
2.
In
a
study
on
potential
local
and
tumorigenic
effects
from
repeated
dermal
application
to
mice
Bronopol
dissolved
in
90%
acetone/
water
was
applied
to
the
shaved
dorsum
of
3
groups
of
mice
(
52
male
and
52
female
per
group)
at
0
(
vehicle
control),
0.2%,
and
0.5%.
Application
was
at
the
rate
of
0.3
ml
per
mouse
on
three
days
(
Monday,
Wednesday,
and
Friday)
in
each
week
for
80
weeks.
The
results
are
summarized
as
follows:
 
Among
some
mice
treated
with
0.5%
Bronopol,
there
was
minimal
hair
loss
at
the
periphery
of
the
shaved
area
during
the
first
three
weeks
of
treatment.
 
A
marginally
inferior
survival
rate
was
recorded
among
male
mice,
although
the
prime
cause
of
death
VerDate
0ct<
31>
2002
19:
49
Dec
23,
2002
Jkt
200001
PO
00000
Frm
00056
Fmt
4703
Sfmt
4703
E:\
FR\
FM\
24DEN1.
SGM
24DEN1
78466
Federal
Register
/
Vol.
67,
No.
247
/
Tuesday,
December
24,
2002
/
Notices
among
decedents
showed
no
relation
to
treatment.
 
Between
weeks
26
and
52,
an
inferior
bodyweight
gain
was
recorded
among
male
mice
treated
with
0.5%
Bronopol,
although
bodyweight
gain
over
the
80
week
treatment
period
was
comparable
with
that
of
the
controls.
Bodyweight
gain
among
other
treated
mice
was
not
disturbed
by
treatment.
 
Food
intake
and
efficiency
of
food
utilization
showed
no
disturbance
by
treatment.
 
Macroscopic
examination
of
decedents
and
mice
killed
after
80
weeks
of
treatment,
revealed
pathology
which
was
common
to
some
animals
from
control
and
treated
groups.
 
Microscopic
examination
of
decedents
and
mice
killed
at
termination
revealed
changes
consistent
with
the
age
and
strain
of
mouse
employed.
 
Treatment
with
Bronopol
did
not
alter
the
spontaneous
tumor
profile
of
the
mice.
6.
Animal
metabolism.
Rat
and
dogs
were
used
in
a
metabolic
study
with
both
oral
and
cutaneous
dosing
as
follows:
Oral
Dosing
in
Rats
was
by
stomach
tube
with
aqueous
solutions
of
[
14C]­
Bronopol
(
1
mg/
kg).
Oral
Dosing
Dogs
­
Beagle
dogs
were
dosed
with
[
14C]­
Bronopol
(
2
mg)
mixed
with
unlabelled
Bronopol
(
6
 
8
mg)
as
an
aqueous
solution
in
gelatin
capsules.
Cutaneous
Dosing
Rats
and
Rabbits
­
Initially
solutions
of
[
14C]­
Bronopol
(
4
mg/
kg)
in
water,
acetone
and
acetone/
water
(
9:
1,
v/
v)
were
applied
to
the
clipped
backs
of
rats
to
determine
the
influence
of
the
vehicle
on
percutaneous
absorption.
Acetone
was
determined
to
be
the
preferred
application
vehicle.
In
the
main
tests
an
acetone
solution
of
[
14C]­
Bronopol
(
4.8
mg/
ml)
was
applied
to
shaved/
depilated
areas
of
the
backs
of
rats
and
rabbits
at
the
rates
of
0.05
ml
per
rat
and
0.2
 
0.4
ml
per
rabbit,
the
treated
areas
being
occluded
with
secured
polythene.
After
an
oral
dose
of
[
14C]­
Bronopol
(
1
mg/
kg)
to
rats
or
dogs,
the
radioactivity
was
completely
absorbed,
evenly
distributed
and
rapidly
excreted.
Excretion
was
almost
complete
in
24
hours.
During
5
days,
rats
excreted
83.3%
in
the
urine,
5.8%
in
the
feces
(
via
the
bile)
and
8.4%
in
the
expired
air;
1.6%
was
still
retained
probably
by
incorporation
into
pathways
of
intermediary
metabolism
of
[
14C]­
glycerol
produced
by
biotransformation
of
[
14C]­
Bronopol.
During
5
days,
dogs
excreted
81.8%
in
the
urine
and
3.1%
in
the
feces.
After
an
oral
dose
of
[
14C]­
Bronopol
(
1
mg/
kg),
peak
blood
levels
of
radioactivity
were
reached
in
rats
and
dogs
within
2
hours,
and
declined
with
an
initial
halflife
of
4
±
1
hour.
After
an
oral
dose
of
[
14C]­
Bronopol
(
1
mg/
kg)
to
the
rat
and
the
dog,
Bronopol
and
its
metabolites
were
evenly
distributed.
Only
in
tissues
concerned
with
excretion
did
levels
of
radioactivity
exceed
those
in
the
blood.
When
applied
to
the
skin
of
rats,
[
14C]­
Bronopol
was
absorbed
to
a
greater
extent
from
an
acetone
solvent
vehicle
than
from
water:
acetone
(
1:
9,
v/
v)
or
water
alone.
In
rats,
at
least
7
and
15%
of
an
applied
dose
was
percutaneously
absorbed
during
24
and
96
hours
respectively.
In
rabbits,
at
least
9%
of
an
applied
dose
was
percutaneously
absorbed
during
24
hours.
Pretreatment
of
rabbit
skin
with
a
depilatory
enhanced
absorption.
Microhistoautoradiographs
of
rabbit
skin
showed
that
[
14C]­
Bronopol
was
mainly
localized
on
the
epidermis
around
the
hair
follicles.
The
limited
percutaneous
absorption
of
Bronopol
may
occur
through
the
hair
follicles.
Five
metabolites,
which
were
more
polar
than
Bronopol,
were
detected
in
the
urine
of
rats
and
dogs
given
an
oral
dose
of
[
14C]­
Bronopol.
One
metabolite,
shown
by
comparison
of
infra­
red
and
mass
spectra
with
synthetic
material
to
be
2­
nitropropane­
1,3­
diol,
accounted
for
more
than
40%
of
the
administered
dose.
Unchanged
Bronopol,
which
is
unstable
in
plasma,
was
not
detected.
A
similar
pattern
of
urinary
metabolites
of
[
14C]­
Bronopol
was
found
after
cutaneous
application
as
after
oral
administration
of
the
compound.
Further
metabolic
studies
were
carried
out
in
male
and
female
rats
following
single
oral
doses
of
[
14C]­
Bronopol
at
10
and
50
mg/
kg
and
repeated
dosing
at
10
mg/
kg/
day
with
Bronopol
for
14
days
followed
by
a
single
oral
dose,
10
mg/
kg
of
[
14C]­
Bronopol.
The
compound
was
well
absorbed
and
rapidly
excreted
mainly
via
urine.
Radioactivity
found
in
the
carcass
and
tissues
at
168
hours
after
dosing
accounted
for
less
than
3%
of
dose.
There
were
no
major
consistent
differences
between
male
and
female
rats.
Bronopol
was
highly
metabolized
and
intact
compound
was
not
detected
in
the
urine.
The
urinary
metabolite
chromatographic
patterns
contained
numerous
polar
metabolites
and
similar
patterns
were
found
for
each
group.
The
major
metabolite
observed
was
equivalent
to
desbromo­
bronopol
(
2­
nitro­
propane­
1,3­
diol).
Extensive
metabolism
led
to
radiolabeled
onecarbon
units
excreted
as
carbon
dioxide
in
expired
air.
7.
Metabolite
toxicology.
As
determined
in
the
animal
metabolism
studies
in
Unit
B.
6.
numerous
polar
metabolites
were
identified
in
urine
from
rat
and
dog.
Unchanged
2­
bromo­
2­
nitro­
1,3­
propanediol
was
not
detected.
The
major
peak
in
most
samples
corresponded
to
desbromobronopol
(
debrominated
bronopol),
i.
e.
2­
nitropropane­
1,
3­
diol.
This
metabolite
is
not
considered
of
toxicological
concern.
8.
Endocrine
disruption.
No
specific
tests
have
been
conducted
with
2­
bromo­
2­
nitro­
1,3­
propanediol
to
determine
whether
the
chemical
may
have
an
effect
in
humans
that
is
similar
to
an
effect
produced
by
a
naturally
occurring
estrogen
or
other
endocrine
effects.
However,
there
were
no
significant
findings
in
other
relevant
toxicity
tests,
i.
e.,
teratology
and
multigeneration
reproduction
studies,
which
would
suggest
that
2­
bromo­
2­
nitro­
1,3­
propanediol
produces
effects
characteristic
of
the
disruption
of
endocrine
functions.

C.
Aggregate
Exposure
1.
Dietary
exposure
 
i.
Food.
The
proposed
use
of
2­
bromo­
2­
nitro­
1,
3­
propanediol
as
a
preservative
in
end­
use
pesticide
formulations
applied
to
growing
crops,
raw
agricultural
commodities
after
harvest,
and
animals
is
not
expected
to
result
in
any
significant
additional,
dietary
exposure,
due
to
the
low
concentration
of
2­
bromo­
2­
nitro­
1,
3­
propanediol
employed
in
the
formulation
and
the
extremely
low
probability
of
significant
contact
by
the
general
public
following
treatment.
2­
bromo­
2­
nitro­
1,
3­
propanediol
has
FDA
approval
for
indirect
food
contact
use
as
a
preservative
in
adhesives
that
are
components
of
food
packaging
or
storage
materials
(
21
CFR
175.105);
as
a
slimicide
for
use
in
pulp
and
papermaking
at
a
maximum
level
of
0.6
lb/
ton
of
dry
weight
fiber
(
21
CFR
176.300);
and
paper
components
in
contact
with
aqueous
and
fatty
foods
at
a
level
not
to
exceed
0.01%
by
weight
of
those
components
(
21
CFR
176.170).
These
uses
are
not
expected
to
result
in
quantifiable
residues
of
2­
bromo­
2­
nitro­
1,
3­
propanediol
in
the
diet.
Uses
as
a
preservative
in
concentrates
of
agricultural
pesticide
products
also
is
not
expected
to
be
a
source
of
quantifiable
residues
in
food.
There
are
no
acute
or
chronic
toxicological
concerns
associated
with
the
proposed
use
of
2­
bromo­
2­
nitro­
1,3­
propanediol
as
an
inert
ingredient
in
concentrates
of
agricultural
pesticide
products.
An
acute
dietary
risk
assessment,
therefore,
is
not
required.
Chronic
exposure
to
2­
bromo­
2­
nitropropane­
1,
3­
diol
through
food
is
essentially
insignificant.
ii.
Drinking
water.
Contamination
of
drinking
water
would
not
be
expected
to
VerDate
0ct<
31>
2002
19:
49
Dec
23,
2002
Jkt
200001
PO
00000
Frm
00057
Fmt
4703
Sfmt
4703
E:\
FR\
FM\
24DEN1.
SGM
24DEN1
78467
Federal
Register
/
Vol.
67,
No.
247
/
Tuesday,
December
24,
2002
/
Notices
occur
under
the
proposed
use
conditions
of
2­
bromo­
2­
nitro­
1,
3­
propanediol
as
a
preservative
at
very
low
concentrations
in
pesticide
products
intended
for
applications,
principally
to
growing
crops,
raw
agricultural
commodities
after
harvest,
and
animals;
as
either
a
direct
pour­
on
application
or
as
a
spray.
Neither
method
of
application
is
expected
to
contaminate
water
supplies
intended
for
human
consumption.
Bronopol
is
not
applied
to
water
and
is
not
used
for
the
disinfection
of
human
or
animal
drinking
water.
2.
Non­
dietary
exposure.
2­
bromo­
2­
nitro­
1,
3­
propanediol
is
used
as
an
industrial
biocide
for
the
prevention
of
biofouling
in
areas
such
as
recirculating
water
in
cooling
towers
and
evaporative
condensers,
air
conditioners,
air
washers
and
humidifier
systems,
oil,
gas
and
industrial
process
water,
metal
working
fluids
and
paper
mill
pulp
and
process
water;
and
for
the
preservation
of
surfactants,
adhesives,
starch,
pigment
and
extender
slurries,
paints,
latex
and
antifoam
emulsions,
absorbent
clays,
water
based
printing
inks
and
print
solutions,
water
based
pesticides
and
chemical
toilet
solutions.
The
margins
of
exposure
(
MOEs)
calculated
for
direct
applicators
occupationally
exposed
by
either
the
dermal
or
inhalation
route,
based
on
worst­
case
estimates,
revealed
there
is
no
level
for
concern.
Estimated
exposures
to
professional
painters
using
paint
preserved
with
2­
bromo­
2­
nitro­
1,
3­
propanediol
were
used
as
the
worst­
case
for
estimating
secondary
occupational
exposure
risk.
MOEs
were
not
exceeded
and
EPA
has
concluded
that
risk
associated
with
secondary
exposure
are
not
of
concern.
2­
bromo­
2­
nitro­
1,
3­
propanediol
is
also
used
in
the
preservation
of
consumer,
household
and
institutional
products.
Based
on
the
worst­
case
estimate
for
professional
painters
chronically
exposed
to
2­
bromo­
2­
nitro­
1,
3­
propanediol,
EPA
has
concluded
that
risk
associated
with
these
uses
are
not
of
concern.
2­
bromo­
2­
nitro­
1,
3­
propanediol
also
is
used
to
preserve
pharmaceuticals,
cosmetics,
and
toiletries,
which
are
regulated
by
FDA.
The
Cosmetic,
Toiletries
and
Fragrance
Association's
(
CTFA's)
Cosmetic
Ingredient
Review
(
1980)
states
that
2­
bromo­
2­
nitro­
1,3­
propanediol
is
safe
as
a
cosmetic
ingredient
at
concentrations
up
to
0.1%
except
where
there
is
a
risk
of
nitrosamine
or
nitrosamide
formation.
Similarly,
2­
bromo­
2­
nitro­
1,3­
propanediol
is
listed
in
Annex
VI
of
the
EC
Cosmetics
directive
as
an
approved
preservative
for
use
up
to
0.1%
except
where
there
is
a
risk
of
nitrosamine
formation.
Based
on
toxicity
data,
an
aggregate
risk
or
likelihood
of
the
occurrence
of
an
adverse
health
effect
resulting
from
all
routes
of
exposure
to
2­
bromo­
2­
nitro­
1,
3­
propanediol
is
not
expected.

D.
Cumulative
Effects
There
is
no
reliable
information
that
would
indicate
or
suggest
that
2­
bromo­
2­
nitro­
1,
3­
propanediol
has
any
toxic
effects
on
mammals
that
would
be
cumulative
with
those
of
any
other
chemical.

E.
Safety
Determination
1.
U.
S.
population.
The
reference
dose
(
RfD)
for
2­
bromo­
2­
nitro­
1,
3­
propanediol
based
on
the
2­
year
chronic
study
(
drinking
water)
in
rats
with
a
NOAEL
of
10
mg/
kg/
day
and
using
an
uncertainty
factor
of
100
is
calculated
to
be
0.1
mg/
kg
of
body
weight
(
bwt)/
day.
The
estimated
worst­
case
theoretical
maximum
residue
contribution
(
TMRC)
resulting
from
this
action
will
be
0.000024
mg/
kg/
bwt/
day
for
the
overall
U.
S.
population
and
represents
0.024
percent
of
the
RfD.
Based
upon
this
information
and
review
of
its
use,
EPA
has
found
that,
when
used
in
accordance
with
good
agricultural
practice,
this
ingredient
is
useful
and
a
tolerance
is
not
necessary
to
protect
the
public
health.
2.
Infants
and
children.
Nothing
in
the
available
literature
would
suggest
that
infants
and
children
are
more
sensitive
to
the
effects
of
2­
bromo­
2­
nitro­
1,
3­
propanediol
than
adults.
Exposure
of
infants
to
2­
bromo­
2­
nitro­
1,
3­
propanediol
resulting
from
its
proposed
use
as
an
inert
ingredient
in
certain
pesticide
formulations
is
expected
to
be
negligible
and
will
not
put
infants
and
children
at
increased
risk.

F.
International
Tolerances
BASF
Corporation
is
not
aware
of
the
existence
of
any
international
tolerances
for
2­
bromo­
2­
nitro­
1,
3­
propanediol.

[
FR
Doc.
02
 
32400
Filed
12
 
23
 
02;
8:
45
am]

BILLING
CODE
6560
 
50
 
S
FEDERAL
RESERVE
SYSTEM
Agency
Information
Collection
Activities:
Proposed
Collection;
Comment
Request
AGENCY:
Board
of
Governors
of
the
Federal
Reserve
System
SUMMARY:
Background.
On
June
15,
1984,
the
Office
of
Management
and
Budget
(
OMB)
delegated
to
the
Board
of
Governors
of
the
Federal
Reserve
System
(
Board)
its
approval
authority
under
the
Paperwork
Reduction
Act,
as
per
5
CFR
1320.16,
to
approve
of
and
assign
OMB
control
numbers
to
collection
of
information
requests
and
requirements
conducted
or
sponsored
by
the
Board
under
conditions
set
forth
in
5
CFR
1320
Appendix
A.
1.
Board
 
approved
collections
of
information
are
incorporated
into
the
official
OMB
inventory
of
currently
approved
collections
of
information.
Copies
of
the
OMB
83
 
I's
and
supporting
statements
and
approved
collection
of
information
instruments
are
placed
into
OMB's
public
docket
files.
The
Federal
Reserve
may
not
conduct
or
sponsor,
and
the
respondent
is
not
required
to
respond
to,
an
information
collection
that
has
been
extended,
revised,
or
implemented
on
or
after
October
1,
1995,
unless
it
displays
a
currently
valid
OMB
control
number.
Request
for
Ccomment
on
Information
Collection
Proposal.
The
following
information
collection,
which
is
being
handled
under
this
delegated
authority,
has
received
initial
Board
approval
and
is
hereby
published
for
comment.
At
the
end
of
the
comment
period,
the
proposed
information
collection,
along
with
an
analysis
of
comments
and
recommendations
received,
will
be
submitted
to
the
Board
for
final
approval
under
OMB
delegated
authority.
Comments
are
invited
on
the
following:
a.
whether
the
proposed
collection
of
information
is
necessary
for
the
proper
performance
of
the
Federal
Reserve's
functions;
including
whether
the
information
has
practical
utility;
b.
the
accuracy
of
the
Federal
Reserve's
estimate
of
the
burden
of
the
proposed
information
collection,
including
the
validity
of
the
methodology
and
assumptions
used;
c.
ways
to
enhance
the
quality,
utility,
and
clarity
of
the
information
to
be
collected;
and
d.
ways
to
minimize
the
burden
of
information
collection
on
respondents,
including
through
the
use
of
automated
collection
techniques
or
other
forms
of
information
technology.
DATES:
Comments
must
be
submitted
on
or
before
February
24,
2003.
ADDRESSES:
Comments
may
be
mailed
to
Ms.
Jennifer
J.
Johnson,
Secretary,
Board
of
Governors
of
the
Federal
Reserve
System,
20th
Street
and
Constitution
Avenue,
N.
W.,
Washington,
DC
20551.
However,
because
paper
mail
in
the
Washington
area
and
at
the
Board
of
Governors
is
subject
to
delay,
please
consider
submitting
your
comments
by
e­
mail
to
regs.
comments@
federalreserve.
gov,
or
VerDate
0ct<
31>
2002
19:
49
Dec
23,
2002
Jkt
200001
PO
00000
Frm
00058
Fmt
4703
Sfmt
4703
E:\
FR\
FM\
24DEN1.
SGM
24DEN1
