Page
of
3
1
UNITED
STATES
ENVIRONMENTAL
PROTECTION
AGENCY
WASHINGTON,
D.
C.
20460
OFFICE
OF
PREVENTION,
PESTICIDES
AND
TOXIC
SUBSTANCES
December
8,
2005
MEMORANDUM
SUBJECT:
Imazapyr.
The
Health
Effects
Division's
(
HED's)
Response
to
Comments
Submitted
During
Phase
One
of
the
Public
Participation
Process.
PC
Code
128821.
CAS
Reg.
No.
81334­
34­
1.
Case
No.
3078.
DP
Barcode
D324105.

FROM:
Christina
M.
Jarvis,
Risk
Assessor
Reregistration
Branch
2
Health
Effects
Division
(
7509C)

THROUGH:
Alan
Nielsen,
Branch
Senior
Scientist
Reregistration
Branch
2
Health
Effects
Division
(
7509C)

TO:
Sherrie
Kinard,
Chemical
Review
Manager
Special
Review
Branch
Special
Review
and
Reregistration
Division
(
7508C)

Summary:

The
attached
document
has
been
generated
to
address
comments
submitted
by
the
registrant
(
BASF
Corporation)
to
the
Agency
on
the
preliminary
HED
risk
assessment
for
imazapyr
(
HED
document
D320583,
9/
20/
2005).
The
attached
document
represents
HED's
response
to
these
comments,
and
includes
input
from
David
Anderson,
Ph.
D.,
(
toxicology),
Charles
Smith
(
occupational/
residential
exposure
assessment),
and
Christina
Jarvis
(
risk
assessment).

Introduction:
Page
of
3
2
The
following
represents
HED's
response
to
the
comments
submitted
by
BASF
Corporation
during
Phase
1
of
the
reregistration
process
for
imazapyr.
Comments
made
by
BASF
are
summarized
by
discipline
(
toxicology,
occupational/
residential
exposure,
and
drinking
water)
with
HED's
response
immediately
following.

Toxicology:

BASF
Comment:
The
summary
of
the
combined
chronic
toxicity/
carcinogenicity
study
in
rats
(
page
25
of
HED's
preliminary
risk
assessment
document)
does
not
reflect
the
conclusions
stated
in
other
parts
of
the
document.
The
3rd
paragraph
states
that
the
study
is
unacceptable
and
does
not
satisfy
the
guideline
requirement
for
a
chronic/
carcinogenicity
study.
In
contrast,
the
conclusion
in
table
4.1b,
page
17,
is
that
the
study
is
acceptable,
with
a
footnote
explaining
that
the
study
is
acceptable
based
on
additional
documentation.
The
5th
paragraph
reinforces
that
the
dosing
was
not
adequate,
but
there
is
no
mention
that
the
policy
that
stated
the
limit
dose
was
published
after
the
study
was
completed.
This
is
stated
in
the
dose
selection
discussion
on
the
last
bullet
point
on
page
28.

HED
Response:
BASF's
comment
is
accepted.
The
combined
chronic
toxicity/
carcinogenicity
study
was
unacceptable
to
the
reviewer,
but
was
later
upgraded
to
acceptable
by
the
Cancer
Assessment
Review
Committee.
The
HED
chapter
of
the
imazapyr
RED
(
9/
20/
2005,
D320583)
will
be
modified
appropriately.

BASF
Comment:
The
toxicological
data
requirements
table
lists
90­
day
dermal
and
inhalation
studies
as
satisfied.
Is
that
appropriate
since
we
have
not
performed
these
studies?

HED
Response:
The
sub
chronic
dermal
and
inhalation
studies
are
not
required
by
the
use
pattern
of
imazapyr
and
do
not
need
to
be
satisfied.
The
table
will
be
updated
accordingly
(
i.
e.,
"
yes"
will
be
changed
to
"
no"
in
the
"
Satisfied"
column).

BASF
Comment:
Page
47,
Section
9.1.4,
Imazapyr
Non­
Cancer
Risk
Summary.
The
first
sentence
states
that
the
total
MOE
was
calculated
from
a
neurotoxicity
endpoint,
when
in
fact,
the
endpoint
was
selected
based
on
skeletal
muscle
effects
seen
in
dogs
with
the
structural
analog
Imazapic.

HED
Response:
BASF's
comment
is
accepted.
Although
skeletal
muscle
effects
are
frequently
associated
with
neurotoxicity,
in
this
case
the
microscopic
examination
of
tissue
from
the
spinal
cord
and
peripheral
nerves
from
the
analogue
showed
no
effects.
"
Skeletal
muscle
endpoint"
will
be
substituted
for
"
neurotoxicity
endpoint"
in
the
sentence.
The
HED
chapter
of
the
imazapyr
RED
(
9/
20/
2005,
D320583)
will
be
modified
appropriately.

Occupational/
Residential
Exposure:
Page
of
3
3
BASF
Comments:
BASF
notes
that
on
pages
39
and
40
of
the
risk
assessment
document,
the
application
rates
in
Tables
6.3b,
6.3c,
and
6.3d
should
be
changed
from
`
1.5
lb
ai/
acre'
to
`
1.5
lb
ae/
acre'.

HED
Response:
BASF's
comment
is
accepted.
The
HED
chapter
of
the
RED
(
9/
20/
2005,
D320583)
will
be
modified
appropriately.

BASF
Comment:
Page
45,
Section
9.1,
Occupational
Exposure.
The
last
sentence
states
that
the
toxicological
endpoint
used
for
inhalation
exposures
was
from
an
inhalation
study,
when
in
fact,
it
is
from
an
oral
study.

HED
Response:
BASF's
comment
is
accepted.
The
HED
chapter
of
the
imazapyr
RED
(
9/
20/
2005,
D320583)
will
be
modified
appropriately.

BASF
Comment:
Page
47
and
49,
Sections
9.1.5
and
10.2.
These
sections
identify
a
data
gap
for
estimating
the
exposure
to
workers
during
helicopter
applications
to
aquatic
sites.
PHED
scenario
#
9
is
available
for
estimating
the
exposure
to
applicators
using
closed
cab
rotary
wing
aircraft.
The
gap
should
be
limited
to
the
use
for
"
open
cab
helicopters"
at
aquatic
sites.

HED
Response:
The
dataset
currently
available
for
estimating
exposure
to
applicators
using
rotary
wing
aircraft
contains
only
three
replicates.
HED
believes
this
data
is
of
poor
quality
and
should
not
be
utilized
in
the
risk
assessment.
As
a
result,
the
rotary
wing
aircraft
scenario
was
considered
to
be
a
data
gap.
HED
will
consider
any
data
BASF
can
provide
regarding
this
particular
scenario.

Drinking
Water
Assessment:

BASF
Comment:
The
data
presented
in
Table
6.2b
of
the
HED
chapter
of
the
imazapyr
RED
(
9/
20/
2005,
D320583)
are
wrong
since
the
information
was
not
correctly
transferred
from
the
EFED
chapter.
BASF
suggests
the
table
be
corrected.

HED
Response:
BASF's
comment
is
accepted.
The
HED
chapter
of
the
imazapyr
RED
(
9/
20/
2005,
D320583)
will
be
modified
appropriately.

BASF
Comment:
The
Agency
chose
to
use
FIRST
as
the
aquatic
exposure
estimation
model.
EPA
has
a
suitable
Forestry/
Non­
crop
Tier
II
scenario
that
BASF
has
used
to
estimate
aquatic
exposure.
BASF
supports
the
use
of
these
corrected
PRZM/
EXAMS
concentrations.

HED
Response:
HED's
acknowledges
BASF's
comment;
however,
this
comment
does
not
fall
within
the
scope
of
"
error
only"
and
rather
will
be
addressed
in
a
forthcoming
Phase
of
the
Reregistration
Eligibility
Decision
(
RED)
process
for
imazapyr.
