Document ID: EPA-HQ-OPP-2002-0079-0012
Agency: epa
Document Type: Supporting & Related Material
Title: 
Posted Date: 2002-06-19T04:00Z

Mr.
Dirk
Helder
April
30,
2002
April
30,
2002
helder.
dirk@
epa.
gov
F
1
703­
305­
4610
Mr.
Dirk
Helder,
Linuron
Chemical
Review
Manager
U.
S.
EPA
OPP/
SRRD
(7508C)
1921
Jefferson
Davis
Highway
Room
266A,
Crystal
Mall
#2
Arlington,
VA
22202­
4501
SUBJECT:
LINURON
TRED
­
RESPONSE
TO
DRAFT
HED,
RESIDUE
AND
DRINKING
WATER
CHAPTERS
Dear
Mr.
Helder:

The
purpose
of
this
letter
is
to
respond
to
the
subject
chapters
received
by
GRIFFIN
LLC
on
February
11,
2002.
We
have
reviewed
the
documents
and
limited
our
responses
to
apparent
discrepancies
between
the
studies
we
have
in
hand
and
the
draft
chapters.

Response
to:
HED
Chapter
of
the
Linuron
Tolerance
Reassessment
Eligibility
Decision.
PC
Codes:
035506.
Case
0047.
DP
Barcode
D271950.

There
are
several
discrepancies
in
the
series
of
documents
prepared
to
support
the
Tolerance
Reassessment
Eligibility
Decision
of
Linuron.
Many
are
basic
to
the
decisions
which
will
be
made
for
additional
studies
and
the
risk
assessment
process.
These
need
to
be
addressed
before
any
of
these
reports
are
published.

1)
The
first
discrepancy
is
the
statement
on
page
4
that
linuron
exhibits
developmental
concerns.
On
page
3
of
the
same
document
it
states:

Developmental
studies
in
the
rat
and
rabbit
showed
no
quantitative
or
qualitative
susceptibility
in
the
offspring.
…
These
findings
do
not
indicate
increased
susceptibility
because
increases
in
resorptions
were
marginal
and
there
was
no
change
in
the
number
of
live
fetuses
to
corroborate
the
increase
in
post­
implantation
losses.

This
is
in
direct
contradiction
with
the
statements
that
there
are
developmental
toxicity
concerns.
In
addition,
the
acute
dietary
endpoint
was
`derived
from
the
developmental
toxicity
study
in
the
rat
and
is
based
on
increases
in
post­
implantation
loss
and
litter/
fetal
resorptions."
(page
5)
Although
the
acute
dietary
endpoint
is
correctly
set
at
12.1
mg/
kg/
day,
it
should
be
based
on
the
NOEL
for
maternal
toxicity
seen
in
this
study
at
12.1
mg/
kg/
day.

2)
The
second
error
was
the
use
of
the
3­
generation
rat
study.
This
study
was
deemed
`supplemental'
because
it
was
a
non­
guideline
study.
Substantial
effort
was
expended
by
DuPont,
the
former
registrant,
to
upgrade
this
study
in
the
late
1980's.
The
Agency,
after
multiple
responses,
would
not
consider
this
study
as
acceptable
or
guideline
compliant
(CAS
#
004405,
Record
#
154,911,
CAS#
004819,
CAS#
005626,
CAS#
008113,
CAS#
008612).
After
a
meeting
held
on
July
22,
1987,
a
new
2­
generation
reproduction
study
in
rats
was
required.
No
records
of
additional
scientific
reviews
can
be
located
which
reverses
this
decision.
This
new
2­
generation
study
was
submitted
with
subsequent
studies
to
elucidate
questionable
effects.
This
study
with
the
amendments
was
accepted,
therefore,
this
study
should
be
used
for
regulatory
decision­
making
and
the
rejected
study
discounted.
Mr.
Dirk
Helder
April
30,
2002
Page
2
The
report
states
on
page
4:

A
3­
generational
study
using
rats
showed
reduced
body
weights
and
fertility,
decreased
pup
survival,
and
decreased
weanling
body,
liver
and
kidney
weights,
as
well
as
liver
atrophy.
The
Hazard
Identification
Assessment
Review
Committee
(HIARC)
determined
that
these
results
illustrate
qualitative
susceptibility
in
the
rat
offspring.

In
the
discussion
of
the
3­
generational
study
in
the
HED
Toxicology
Disciplinary
Chapter
the
LOEL
for
systemic
toxicity
was
established
at
125
ppm
and
the
NOEL
was
set
at
25
ppm.
The
offspring
toxicity
LOEL
was
established
at
625
ppm
with
the
NOAEL
at
125
ppm.
This
was
based
on
decreased
pup
survival
and
lower
pup
body
weights.
It
is
clear
that
this
effect
was
at
maternally
toxic
levels.
This
is
NOT
evidence
of
a
qualitative
susceptibility
in
rat
offspring.

EPA's
position
was
very
clearly
stated
in
the
August
15,
1985
rebuttal
comments
from
James
N.
Rowe.
(Record
Number
154,911).
It
states:

"It
is
apparent
that
gross
and
histopathological
examinations
of
the
adult
rats
were
not
performed
by
the
registrant.
Therefore,
proper
interpretation
of
the
reproductive
effects
observed
in
the
study
cannot
be
performed."

In
addition,
meeting
minutes
from
a
discussion
between
DuPont
and
the
Agency's
scientists
held
on
July
22,
1987
(in
the
public
docket)
make
it
clear
that
in
addition
to
the
lack
of
histopathological
data,
fewer
than
20
animals
per
group
were
tested
which
were
fewer
than
guideline
specification.

Griffin
LLC
can
only
assume
an
error
was
made
in
reviewing
the
classification
of
the
acceptable/
guideline
designation
or
the
study
was
re­
evaluated
and
given
a
new
assessment.
If
there
is
a
new
review,
the
Agency
has
not
notified
the
registrant.
Regardless,
a
significant
discrepancy
exists.

3)
The
third
major
discrepancy
is
the
determination
of
a
`neurotoxicity'
concern.
There
has
never
been
an
Agency
concern
for
neurotoxicity
induced
by
linuron.
The
Agency
previously
recognized
this
in
that
no
acute
or
subchronic
neurotoxicity
studies
were
requested.
Linuron
has
been
shown
to
be
an
endocrine
disruptor.
This
has
never
been
in
question.
There
is,
however,
a
big
difference
between
the
weak
anti­
androgenic
activity
elicited
by
linuron
and
`neuroendocrine'
effects
referred
to
by
the
Agency
in
this
document.
No
data
have
been
presented
by
the
Agency
either
from
registrant
sponsored
studies
or
from
the
literature
which
would
be
a
basis
for
a
neurotoxicity
concern.
This
designation
of
"neuroendocrine
effects"
has
no
scientific
basis
and
should
be
either
deleted
from
the
document
or
supported
somewhere
in
the
scientific
documents.
The
request
for
a
developmental
neurotoxicity
test
is
not
supported
by
the
Agency's
own
assessment
of
the
science.
(see
discussion
above
as
it
relates
to
the
developmental
studies)

4)
The
fourth
major
discrepancy
is
the
reference
with
Linuron
(and
subsequent
regulatory
action)
to
linuron
as
an
inhalation
concern.
There
is
essentially
no
toxicity
by
the
inhalation
route.
The
LD50
is
>218
mg/
L
or
21.8
g/
M
3
.
The
MOEs
calculated
in
the
Linuron
RED
of
March
1995
were
all
above
100
and
of
no
concern.
These
were
based
on
the
NOELs
(12.1
mg/
kg)
from
the
rat
developmental
study
for
the
short­
term
assessment
and
the
2­
generation
reproduction
study
(1.25
mg/
kg/
day)
for
the
intermediate
term
assessment.
Because
the
occupational
exposure
to
a
pre­
emergent
herbicide
used
once
per
season/
year
will
not
exceed
30
days
exposure,
there
is
not
a
great
inhalation
risk
concern
driven
by
the
use
patterns.
In
addition,
linuron
is
neither
volatile
as
an
active
ingredient
nor
contains
volatiles
nor
becomes
volatile
in
its
formulations.
Given
the
lack
of
inhalation
toxicity
and
Mr.
Dirk
Helder
April
30,
2002
Page
3
potential
for
exposure,
the
request
for
a
28­
day
inhalation
study
is
not
supported.
This
is
either
in
error
or
requires
scientific
justification.

Response
to
EPA
Document:
Linuron
TRED
Residue
Chemistry
Considerations
There
are
two
discrepancies
in
the
series
of
documents
prepared
to
support
the
Tolerance
Reassessment
Eligibility
Decision
of
Linuron.
Many
are
basic
to
the
decisions
which
will
be
made
for
additional
studies
and
the
risk
assessment
process.
These
need
to
be
addressed
before
any
of
these
reports
are
published.

5)
Page
46.
Miscellaneous
Commodities
"Cotton,
seed
and
gin
products
For
the
gin
byproducts
field
trials,
information
describing
the
type
of
equipment
used
for
harvesting
in
the
machine­
harvest
trials
must
be
submitted.
In
addition,
additional
cotton
gin
byproducts
field
trials
must
be
conducted,
such
that
the
requirements
of
GLN
860.1000
(Table
1)
for
gin
byproducts
field
trials
are
fulfilled,
or
a
justification
for
the
substitution
of
data
from
field
trials
reflecting
hand
harvesting
must
be
submitted."

A
response
to
the
issues
raised
above
was
submitted
to
Mr.
Tom
Myers,
Chemical
Review
Manager.
The
letter
of
transmittal
is
dated
January
14,
2002
and
was
sent
via
FedEx
on
this
date.
Our
records
indicate
that
this
response
was
received
on
January
16.

6)
Page
47.
Magnitude
of
the
Residue
in
Processed
Food/
Feed
"The
2/
94
RED
and
2/
95
RED
Addendum
concluded
that
additional
data
were
required
to
upgrade
an
existing
potato
processing
study
(S.
Knizner,
9/
2/
92);
these
data
remain
outstanding."

A
response
to
the
memorandum
from
Steven
A.
Knizer
to
Lois
Rossi
was
submitted
to
the
Agency
on
February
14,
2000.
Our
records
show
that
the
response
was
received
by
the
Agency
on
February
18,
2000.
The
information
requested
for
upgrading
this
study
was
included
in
the
submittal.

Response
to
Linuron
TRED,
Drinking
Water
There
are
two
discrepancies
in
the
series
of
documents
prepared
to
support
the
Tolerance
Reassessment
Eligibility
Decision
of
Linuron.
Many
are
basic
to
the
decisions
which
will
be
made
for
additional
studies
and
the
risk
assessment
process.
These
need
to
be
addressed
before
any
of
these
reports
are
published.

Surface
Water
7)
Model
used
for
estimating
residues
in
drinking
water
The
Agency
used
the
IR­
PCA
PRZM/
EXAM
model
that
has
never
been
validated
and
has
been
proven
to
grossly
overestimate
residues
in
drinking
water.
It
is
stated
in
the
document
that
"Modeling
results
are
higher
than
those
from
existing
surface
water
monitoring
data
for
linuron
targeted
to
the
pesticide
use
area".
Percent
Crop
Area
(PCA)
was
used
in
the
modeling
of
linuron
on
carrots.
PCA
is
only
applicable
to
major
crops
and
carrots
in
the
San
Joaquin
–Tulare
Basins
is
not
considered
a
major
crop.
Data
from
the
1992
Census
of
Agriculture
were
used
to
generate
the
PCA's
and
recent
changes
in
the
agriculture
sector
has
significantly
impacted
the
distribution
of
crops
throughout
the
US.
We
feel
that
the
IR­
PCA
PRZM/
EXAM
model
is
not
a
valid
modeling
system
for
estimating
residues
in
drinking
water
and
that
the
inputs
into
the
model
are
not
valid.
The
results
from
this
model
misrepresent
the
actual
residues
that
Mr.
Dirk
Helder
April
30,
2002
Page
4
occur
in
drinking
water.
Monitoring
data
cited
by
the
Agency
much
more
accurately
reflects
linuron
residues
in
drinking
water.

Ground
Water
8)
The
Agency
recommended
that
5
ppb
of
linuron
be
used
in
the
drinking
water
assessment
based
on
monitoring
data
cited.

It
is
recommended
in
this
document
that
5
ppb
be
used
in
the
drinking
water
assessment
in
ground
water.
Data
cited
in
the
review
show
that
the
highest
residue
in
drinking
water
was
5
ppb.
We
recommend
that
the
Agency
use
in
their
drinking
water
assessment
an
average
residue
from
the
water
monitoring
data.
Data
cited
by
the
Agency
from
a
USGS
NAWQA
monitoring
study
show
linuron
residues
were
detected
in
only
0.11%
of
the
924
samples
analyzed.
The
maximum
concentration
was
0.029
ppb.
In
another
study
cited,
linuron
residues
were
present
in
29%
of
the
377
analyses.
The
highest
residue
from
this
monitoring
study
was
5
ppb.
Again,
the
Agency
is
using
a
value
that
grossly
overestimates
linuron
residues
in
drinking
water.
If
an
average
residue
value
is
used,
then
the
estimated
exposure
would
be
<1
ppb.

Additional
monitoring
data
can
be
found
at
the
following
website:
http://
water.
wr.
usgs.
gov/
pnsp/
pestgw/

In
this
monitoring
program,
water
samples
were
collected
from
1243
wells
and
1849
aquifers
located
in
agricultural
areas.
Linuron
residues
were
detected
in
0.16%
of
the
wells
and
0.05%
of
the
aquifers.
The
maximum
linuron
residue
detected
in
these
water
samples
was
0.03
ppb.
Water
samples
were
also
collected
from
643
wells
in
urban
areas
and
no
residues
were
detected
in
any
of
the
water
samples
analyzed.

Please
advise
if
any
additional
draft
Linuron
chapters
will
be
distributed.

Sincerely
yours,

Wm.
Ronald
Landis,
Ph.
D.
Consultant
to
GRIFFIN,
LLC
pc:
Richard
Collier,
Ph.
D.,
GRIFFIN,
LLC
Bill
Tweedy,
Ph.
D.,
GRIFFIN,
LLC
Jimmy
Lefiles,
GRIFFIN,
LLC
Gail
Arce,
Ph.
D.,
GRIFFIN,
LLC