Document ID: EPA-HQ-OPP-2005-0258-0044
Agency: epa
Document Type: Supporting & Related Material
Title: 
Posted Date: 2006-08-30T04:00Z

UNITED
STATES
ENVIRONMENTAL
PROTECTION
AGENCY
WASHINGTON,
D.
C.
20460
OFFICE
OF
PREVENTION,
PESTICIDES
AND
TOXIC
SUBSTANCES
MEMORANDUM
June
20,
2006
SUBJECT:
Triadimefon:
HED
Response
to
Comments
Received
During
the
Public
Comment
Phase
(
Docket
ID
Number
EPA­
HQ­
OPP­
2005­
0258/
Closed
4/
17/
06).

DP
Barcode:
328262
FROM:
Richard
Griffin,
Risk
Assessor
Reregistration
Branch
II
Health
Effects
Division
(
HED)

THROUGH:
Alan
Nielsen,
Branch
Senior
Scientist
Reregistration
Action
Branch
II
Health
Effects
Division
(
7509P)

TO:
John
Pates,
Jr.,
Chemical
Review
Manager
Veronique
Lacapra,
Team
Leader
Reregistration
Branch
I
Special
Review
and
Reregistration
Division
(
7508P)

As
part
of
the
reregistration
process
for
triadimefon,
this
memo
is
the
HED
response
to
public
comments
concerning
the
HED
human
health
risk
assessment
dated
February
9,
2006.
This
response
is
specific
to
the
comments
received
from
the
primary
registrant
(
Bayer
CropScience)
on
April
13,
and
April
17,
2006.
This
memo
also
addresses
comments
received
from
the
U.
S.
Triazole
Task
Force
on
May
17,
2006
concerning
the
2/
15/
06
HED
risk
assessment
for
the
triazole­
derived
metabolites
(
triazole
alanine,
triazole
acetic
acid,
and
1,2,4­
triazole.
Also,
Bayer
CropScience
submitted
a
proposed
triadimefon
dietary
risk
assessment
on
May
8,
2006,
which
is
currently
being
reviewed
by
HED.

The
Bayer
comments,
and
proposed
risk
assessment
revisions,
are
based
on
refinements
to
residue
estimates
for
food
uses,
refinements
to
application
rates
on
turf,
and
refinements
to
the
percent
of
use
on
golf
course
turf.
HED
will
evaluate
each
proposed
2
refinement
for
use
in
the
Agency's
human
health
risk
assessment
for
triadimefon.

General
Comments
1.
As
part
of
the
triadimefon
risk
assessment,
the
Agency
requested
that
references
to
cucurbits
be
removed
from
all
labels.
Bayer
agrees
with
this
requirement,
and
points
out
that
cucurbits
were,
in
fact,
removed
from
all
labels
on
6/
4/
97.

2.
The
Agency
requested
that
product
labels
be
modified
to
specify
that
aerial
applications
to
orchard
crops
be
made
in
a
minimum
of
10
gallons
of
water
per
acre.
Bayer
agrees
with
this
requirement,
and
will
modify
labels
accordingly.

3.
The
Agency
requested
that
product
labels
be
modified
to
specify
the
removal
of
rotational
crop
restrictions.
Bayer
agrees
with
this
requirement
and
will
modify
labels
accordingly.

4.
The
Agency
requested
data
to
correct
a
deficiency
concerning
pineapple
field
trial
data.
Bayer
has
resolved
the
issue
by
identifying
a
report,
submitted
in
1996,
that
addressed
pineapple
field
trials.

Dietary
Risk
5.
Bayer
has
identified
a
typographical
error
in
the
dietary
risk
assessment
memo
of
11/
23/
05
(
the
aPAD
is
listed
as
0.01
mg/
kg/
day
instead
of
the
correct
0.0034
mg/
kg/
day).
The
Agency
notes
the
error
(
the
correct
value
was
used
in
the
Agency
risk
assessment).

6.
The
Agency
estimates
for
acute
dietary
risk
(
food
and
water
sources
combined)
were
710
percent
of
the
aPAD
for
the
population
sub­
group
of
"
all
infants",
and,
as
noted
in
Bayer's
comments,
230
percent
of
the
aPAD
for
the
general
(
or
average)
U.
S.
population.

Bayer
reports
that
a
significant
decrease
in
acute
dietary
risk
estimates
can
be
made
(
with
all
population
sub­
groups
less
than
100%
of
the
aPAD)
if
based
on
revisions
to
residue
estimates
for
food
uses.
Specifically,
Bayer
has
used
PDP
and
FDA
monitoring
data
for
grape
and
raspberry
commodities,
and
processing
data
for
pineapple
juice,
grape
juice,
and
pineapple
pulp.

This
residue
data,
finalized
in
the
May
8
Bayer
dietary
risk
assessment,
is
in
review
in
HED,
and
will
be
used
as
part
of
a
revised
risk
assessment
if
found
appropriate.
Note
however,
that
the
significant
decrease
in
dietary
risk
estimates,
reported
by
Bayer,
are
due
primarily
to
a
revision
to
the
drinking
water
contamination
estimates.

7.
As
noted
above,
The
Agency
estimates
for
acute
dietary
risk
are
based,
in
part,
on
estimates
of
residues
in
drinking
water.
Ground­
and
surface­
sourced
drinking
water
concentrations
may
be
factored
by
estimates
termed
"
Percent
Cropped
Area",
or
PCA,
values
depending
on
available
data.
Lacking
reliable
data,
default
values
of
100%,
for
turf,
and
87%
for
all
other
scenarios
were
used
by
the
Agency.
3
Bayer's
response
to
the
use
of
these
upper­
bound
factors
was
to
gather
data,
from
multiple
U.
S.
States,
concerning
the
percent
of
a
watershed
that
may
be
used
for
golf
courses.
Based
on
limited
data,
Bayer
suggests
a
PCA
factor
of
7.7%
be
used
to
factor
drinking
water
derived
from
surface
sources.
Bayer
also
notes
in
their
response
that
although
the
agricultural
use
of
triadimefon
is
less
than
5%
of
total
use,
the
agricultural
use
will
be
factored
into
surface
water
estimates.
At
his
point,
however,
the
Agency
cannot
agree
to
the
use
of
percent
usage
data
and
will
continue
to
assume
100%
use
on
turf
until
adequate
data
indicate
otherwise.

Worker
Risk
8.
The
Agency
occupational
risk
assessment
indicated
that
some
mixer/
loader
scenarios
using
the
triadimefon
wettable
powder
formulation,
will
have
Margins
of
Exposure
less
than
the
target
level
of
100.
Bayer's
response,
that
exposure
can
be
reduced
significantly,
is
based
on
the
use
of
water­
soluble
packaging
using
poly
vinyl
acetate,
or
PVA.

The
Agency
concurs
that
risk
reduction
can
be
achieved
for
most
wettable
powder
scenarios
if
water­
soluble
packaging
is
used
as
an
engineering
control.
However,
based
on
(
limited)
PHED
data,
two
exposure
scenarios
would
remain
a
concern
even
with
the
assumption
of
maximum
risk
mitigation:
1)
mixing/
loading/
applying
wettable
powders
with
a
low
pressure
handwand
to
turf
(
LCO
and
golf
course)
at
the
5.4
lb
ai/
A
(
CA
only)
application
rate,
where
the
MOE
=
46
with
double
layer
and
gloves
and
a
90%
protection
factor
half­
face
respirator,
and;
2)
mixing/
loading/
applying
wettable
powders
with
a
low
pressure
handwand
to
turf
(
LCO
and
golf
course)
at
the
2.7
lb
ai/
A
(
except
CA)
application
rate,
where
the
MOE
=
92
with
double
layer
and
gloves
and
a
90%
protection
factor
half­
face
respirator.

9.
The
Agency
occupational
risk
assessment
indicated
that
some
mixer/
loader/
applicator
scenarios
for
turf
and
pine
seedling
applications
will
have
MOE
estimates
less
than
the
target
level
of
100.
Bayer
has
commented
that
acceptable
levels
can
be
achieved
by
correcting
the
application
rate
in
turf
from
5.4
lb
ai/
A
to
2.7
lb
ai/
A,
and
by
using
ORETF
exposure
data.

The
Agency,
in
fact,
used
ORETF
for
scenarios
where
it
was
appropriate.
In
regard
to
the
rate
of
5.4
lb
ai/
A,
there
are
several
current
labels
that
contain
the
maximum
5.4
lb
ai/
A
rate
(
for
uses
on
pink
snow
mold
and
gray
snow
mold
in
California
only),
including
Bayleton
50%
WSP
Fungicide,
Bayleton
50%
Wettable
Powder
Fungicide,
Bayleton
50
DF,
and
The
Andersons
1.0%
Bayleton
Fungicide.
When
an
agreement
is
made
to
remove
the
5.4
lb
ai/
A
rate
from
all
the
above
labels,
the
rate
of
2.7
lb
ai/
A
will
serve
as
the
maximum
rate
for
for
the
purposes
of
risk
assessment.

10.
As
part
of
the
occupational
risk
assessment,
the
Agency
included
two
labeled
uses
for
triadimefon,
(
tree
trunk
injection
and
ready­
to­
use
briquettes),
but
in
fact,
there
is
no
exposure
data
on
which
to
base
risk
estimates.
Bayer
returned
comment
by
noting
that
these
two
uses
are
not
uses
registered
by
Bayer.
4
Again,
the
Agency
responds
that
these
are
current
labeled
uses
that
must
remain
in
the
risk
assessment,
unless
an
agreement
is
made
to
remove
these
uses
from
all
labels.

11.
Also,
as
part
of
the
occupational
risk
assessment,
the
Agency
included
a
use
registered
to
Bayer;
a
dip
treatment.
As
the
case
with
the
uses
mentioned
above,
there
is
no
reliable
data
on
which
to
base
exposure/
risk
estimates.
Bayer
commented
that
a
risk
assessment
can
be
prepared
for
a
dip
treatment
using
surrogate
data
from
a
worse­
case
scenario,
such
as
commercial
pine
seed
treatment.

However,
the
Agency
does
not
agree
that
using
surrogate
data
from
a
worse­
case
scenario
such
as
commercial
pine
seed
treatment
would
be
appropriate
because
dip
applications
are
likely
to
involve
significant
exposure
to
liquids.
Instead,
the
Agency
proposes
to
mitigate
possible
risk
concerns
from
this
application
method
by
a
label
requirement
for
the
use
of
protective
equipment
("
baseline"
attire
plus
chemical­
resistant
gloves
and
a
chemical­
resistant
apron).

12.
The
Agency's
assessment
of
the
use
of
triadimefon
for
the
treatment
of
ponderosa
pine
seed
indicated
an
exposure
concern
for
all
activities
believed
to
be
associated
with
this
scenario.
In
order
to
refine
the
risk
estimates
for
this
scenario,
Bayer
has
provided
information
from
Auburn
University's,
Scott
Enebak,
that
describes
the
entire
pine
seed
treatment
process.
It
is
important
to
note
that
Dr.
Enebak's
assessment
that
a
typical
nursery
will
treat
300
to
500
lbs
of
seed
per
day
with
a
maximum
of
1,000
lbs
per
day
(
if
more
than
one
mixer
is
used)
is
significantly
different
than
the
Agency'S
estimation
of
12,485
pounds
of
seed
treated
per
day.

The
Agency
notes
the
information
provided
by
Dr.
Enebak
was
useful
and,
has
added
this
application
method
to
the
"
on­
nursery"
assessment
for
treated
pine
seeds.
However,
the
assessment
for
the
hopper­
box
and
planter­
box
scenarios
will
be
retained
since
there
is
no
information
that
these
techniques
are
not
used
to
treat
pine
seeds.
EPA
notes
that
the
risks
of
concern
for
the
pine
seed
assessment
were
from
the
commercial
treatment
of
pine
seeds.
The
information
provided
by
Bayer
did
not
impact
the
commercial
pine
seed
assessment
and
these
risks
remain
an
issue
for
reregistration.

Residential
/
Application
Risk
13.
The
Agency's
risk
assessment
for
residential
turf
was
based
on
the
application
rate
of
5.2
lb
ai/
acre.
Bayer
has
commented
that
the
Agency
has
over­
estimated
risk
from
turf
use
since
the
actual
maximum
rates
are
2.7
pounds
ai/
acre
on
golf
courses
and
1.3
pounds
ai/
acre
on
residential
turf.

Currently
there
are
several
labels,
including
labels
intended
for
occupational
application
to
residential
sites
and
labels
primarily
intended
for
homeowner
application
to
home
lawns
that
contain
the
maximum
5.4
lb
ai/
A
rate
for
use
on
pink
snow
mold
and
gray
mold
in
California
(
only)
and
contain
a
2.7
lb
ai/
A
rate
as
the
maximum
rate
for
uses
on
turf
outside
of
California.
Examples
of
such
labels
include
Bayleton
50%
WSP
Fungicide,
Bayleton
50%
Wettable
Powder
Fungicide,
Bayleton
50
DF,
and
The
5
Andersons
1.0%
Bayleton
Fungicide.
Therefore,
EPA
will
continue
to
assess
the
risks
at
the
5.4
lb
ai/
A
rate
for
California,
and
will
add
the
2.7
lb
ai/
A
rate
as
the
maximum
rate
for
uses
on
turf
outside
of
California.
The
1.3
lb
ai/
A
rate
will
be
used
as
Bayer's
proposed
maximum
application
rate
for
residential
sites,
(
including
lawns,
parks,
recreation
areas,
athletic
fields,
school
grounds,
etc).

Residential
/
Postapplication
Risk
14.
The
Agency's
post­
application
risk
estimates
(
MOEs)
for
many
adult,
youth,
and
children's
exposure
scenarios
are
below
the
target
risk
level
of
1,000.

Bayer
comments
that
the
adult
and
youth
postapplication
risk
assessments
can
be
refined
to
"
acceptable"
MOEs
by
using
the
correct
application
rate
of
1.3
lb
ai/
A
and
by
using
data
from
the
Bayer
study
Evaluation
of
Potential
Exposure
Resulting
from
Contact
with
Bayleton­
Treated
Turf,
MRID
43125401.
Child
postapplication
scenarios,
except
incidental
ingestion
of
granules
or
pellets,
can
be
refined
to
generally
acceptable
MOEs
by
using
the
1.3
lb
ai/
A
rate
and
the
Bayer
study.
By
using
the
1.3
lb
ai/
A
rate,
the
child
incidental
ingestion
of
granules
or
pellets
scenario
can
be
improved.
However,
the
Bayer
study
does
not
apply
to
this
(
oral
dose)
scenario.

The
Agency
has
used
both
the
"
turf
transferable"
(
TTR)
residue
values
and
transfer
coefficients
from
the
Bayer
study
to
assess
the
risk
for
high
contact
dermal
activities
on
lawns.
EPA's
Standard
Operating
Procedures
for
Residential
Exposure
Assessments
indicates
that
default
TTR
values
of
five
and
twenty
percent
should
be
used
to
assess
incidental
oral
exposures
and
from
hand­
to­
mouth/
object­
to­
mouth
scenarios,
respectively.
Therefore,
EPA
has
not
revised
the
risk
assessment
for
incidental
oral
exposures
to
toddlers.
EPA
has
assessed
risk
using
the
5.4
lb
ai/
A
rate
(
CA
only),
the
2.7
lb
ai/
A
rate
(
outside
of
CA)
and
Bayer's
proposed
1.3
lb
ai/
A
rate
for
residential
sites.

EPA
notes
that
even
with
the
proposed
1.3
lb
ai/
A
rate
and
the
use
of
the
Bayer
turf
study,
risk
remains
a
concern
for
toddlers.
Only
one
scenario,
incidental
soil
ingestion,
had
MOEs
>
1,000.
Short­
term
MOEs
were
<
1,000
for
residential
turf/
high
contact
activities,
hand­
to­
mouth
activities,
object­
to­
mouth
activities,
and
incidental
ingestion
of
granules/
pellets.

Toxicology
/
Endpoints
/
Dose
Selection
15.
The
triadimefon
risk
assessment's
toxicology
data
requirement
table
listed
the
requirement
for
a
90­
day
inhalation
study
as
"
not
satisfied."
In
their
response
memo,
Bayer
questions
the
need
and
scientific
rationale
for
this
study.
The
Agency
will
amend
the
data
requirement
table
to
reflect
that
an
inhalation
study
is
not
required
at
this
time.
Other
corrections
to
the
toxicology
requirement
table
will
be
made
as
appropriate.

16.
For
triadimefon
risk
assessment,
HED
selected
the
subchronic
neurotoxicity
study
as
the
basis
for
the
acute
(
dietary)
reference
dose,
the
chronic
(
dietary)
reference
dose,
the
"
incidental"
oral
dose,
and
the
inhalation
exposure
dose.
Bayer
agrees
with
the
study
6
selected,
but
states
that
the
dose
used
for
risk
assessment,
or
Point
of
Departure
(
POD)
may
be
several­
fold
higher
than
the
NOAEL
used
for
risk
assessment.
When
Bayer
submits
this
proposal
the
Agency
will
review
it
as
soon
as
possible.

17.
As
the
case
with
triadimefon,
Bayer
agrees
with
the
Agency's
use
of
the
triadimefon
subchronic
neurotoxicity
study
for
acute
(
aPAD)
and
chronic
(
cPAD)
dietary
risk
assessment,
for
"
incidental"
oral,
and
for
inhalation
risk
assessment.
Bayer,
however,
believes
that
the
dose
level,
or
"
Point
of
Departure,"
may
be
several­
fold
higher
than
the
NOAELs
reported
in
these
studies.
Bayer
indicates
they
are
currently
evaluating
the
data
from
this
study
to
assess
the
appropriate
POD
for
risk
assessment.

18.
Bayer's
concluding
comments
to
the
Agency's
risk
assessment
for
triadimefon
concern
toxicology
requirements:

Bayer
notes
the
21­
day
dermal
toxicity
study,
listed
as
not
required
by
the
Agency,
should
be
required.
The
Agency
agrees
and
the
21­
day
study
is,
in
fact,
required
for
triadimefon.

Bayer
notes
the
90­
day
inhalation
toxicity
study,
listed
as
required,
is
not
discussed
in
the
risk
assessment.
The
Agency
agrees
with
Bayer,
and
a
rationale
will
be
provided
in
a
revised
risk
assessment
for
triadimefon.

Bayer
notes
the
acute
neurotoxicity
screening
study,
reviewed
by
the
Agency,
satisfies
the
guideline
870.6200a
requirements.
The
Agency
agrees
with
Bayer
on
this
issue
and
does
not
currently
require
a
new
acute
neurotoxicity
screening
study
(
and
will
correct
the
toxicology
requirements
able).

Bayer
notes
the
developmental
neurotoxicity
study,
listed
as
not
required,
is
actually
now
required,
with
the
rationale
for
requirement
in
the
toxicology
section
of
the
risk
assessment.
The
Agency
concurs
with
this,
and
a
developmental
neurotoxicity
is
currently
required
(
and
the
table
will
be
corrected
to
show
this).

Bayer
notes
the
dermal
penetration
study,
listed
as
required,
is
not
actually
needed
for
risk
assessment,
since
the
15­
day
dermal
toxicity
study
is
an
acceptable
guideline
study.
The
Agency
agrees
with
Bayer
on
this
issue
and
does
not
currently
require
a
new
dermal
penetration
study.

Bayer
notes
the
list
of
special
ocular
effects
in
the
toxicology
requirement
table
and
believes
it
is
not
appropriate
to
include
these.
The
Agency
re­
states
that
these
studies
are
not
required
for
triadimefon.

U.
S
Triazole
Task
Force
Comments:

1.
The
Task
Force
notes
that
on
page
38,
Tables
6.5,
6.6,
6.7,
and
6.8,
(
of
the
triazole
risk
assessment)
the
listed
application
rate
for
triadimefon
is
5.4
lbs
a.
i./
acre
and
this
value
is
incorrect.
The
actual
maximum
application
rate
for
Bayer's
product
7
Bayleton
50
is
5.5
lb.
product/
acre.
Since
the
product
Bayleton
50
is
50%
triadimefon,
the
actual
rate
of
triadimefon
application
is
2.75
lb
a.
i./
acre.
This
error
results
in
a
twofold
increase
in
the
calculated
residential
exposure
values
utilized
in
the
assessments.

EPA:
Currently,
there
are
several
labels
that
contain
the
maximum
5.4
lb
ai/
A
rate
(
for
uses
on
pink
snow
mold
and
gray
snow
mold
in
California
only),
including
Bayleton
50%
WSP
Fungicide,
Bayleton
50%
Wettable
Powder
Fungicide,
Bayleton
50
DF,
and
The
Andersons
1.0%
Bayleton
Fungicide.
The
labels
state
that
a
maximum
of
4
ounces
can
be
applied
per
1,000
square
feet.
That
application
rate
converts
to
5.4
pounds
active
ingredient
per
acre.
Therefore,
EPA
will
continue
to
assess
the
risks
at
the
5.4
lb
ai/
A
rate
for
California
only
and
will
add
the
2.7
lb
ai/
A
rate
as
the
maximum
rate
for
uses
on
turf
outside
of
California.

2.
The
Task
Force
notes
that
on
page
42,
Table
7.1:
The
values
listed
under
the
headings
Dermal,
Hand­
to­
Mouth,
Object­
to­
Mouth,
Soil
Ingestion,
Aggregate
and
Aggregate
MOE
for
the
infants
and
children
subgroups
are
incorrect
due
to
the
error
sited
in
comment
#
1.

EPA:
EPA
reiterates
that
it
believes
that
the
5.4
lb
ai/
A
rate
is
on
several
current
triadimefon
labels
as
the
maximum
application
rate
in
California.
EPA
has
added
the
2.7
lb
ai/
A
rate
for
turfgrass
outside
of
California
and
a
1.3
lb
ai/
A
rate
that
Bayer,
in
their
April
2006
comments,
states
is
the
maximum
rate
for
use
on
residential
turf.

3.
The
Task
Force
notes
that
on
page
43,
Table
7.2.
The
values
listed
under
the
headings
Soil
Ingestion,
Aggregate
and
Aggregate
MOE
for
the
infants
and
children
subgroups
are
incorrect
due
to
the
error
sited
in
comment
#
1.

EPA:
EPA
reiterates
that
it
believes
that
the
5.4
lb
ai/
A
rate
is
on
several
current
triadimefon
labels
as
the
maximum
application
rate
in
California.
EPA
has
added
the
2.7
lb
ai/
A
rate
for
turfgrass
outside
of
California
and
a
1.3
lb
ai/
A
rate
that
Bayer,
in
their
April
2006
comments,
states
is
the
maximum
rate
for
use
on
residential
turf.

4.
The
Task
Force
has
submitted
corrected
aggregate
(
residential)
risk
calculations
in
an
attached
Excel
workbook.

EPA:
EPA
will
assess
risks
using
the
5.4
lb
ai/
A
rate
(
CA
only),
the
2.7
lb
ai/
A
rate
(
outside
of
CA)
and
Bayer's
proposed
1.3
lb
ai/
A
rate
for
residential
sites.
EPA
notes
that
even
with
the
proposed
1.3
lb
ai/
A
rate
and
the
use
of
the
Bayer
turf
study,
risk
remains
a
concern
for
toddlers.
Only
one
scenario,
incidental
soil
ingestion,
had
MOEs
>
1,000.
Short­
term
MOEs
were
<
1,000
for
residential
turf/
high
contact
activities,
handto
mouth
activities,
object­
to­
mouth
activities,
and
the
"
incidental"
ingestion
of
granules/
pellets.
EPA
notes
that
the
U.
S.
Triazole
Task
Force
calculations
used
a
dermal
absorption
factor
to
calculate
dermal
risks.
EPA
is
assessing
risks
using
the
toxicological
endpoint
from
a
dermal
study