Page
1
of
105
UNITED
STATES
ENVIRONMENTAL
PROTECTION
AGENCY
WASHINGTON,
D.
C.
20460
OFFICE
OF
PREVENTION,
PESTICIDES
AND
TOXIC
SUBSTANCES
MEMORANDUM
Date:
11/
23/
05
SUBJECT:
Triadimefon.
Preliminary
Human
Health
Risk
Assessment
PC
Code:
109901
DP
Barcode:
D281838
Case
No:
2700
Regulatory
Action:
Phase
1
Reregistration
Risk
Assessment
Type:
Single
Chemical
Aggregate
FROM:
Richard
Griffin,
Risk
Assessor
Reregistration
Branch
II
Health
Effects
Division
(
HED)

And
Judy
Facey,
Toxicology
Shanna
Recore,
Occupational/
Residential
Assessment
Yvonne
Barnes,
Product
Chemistry
Sam
Ary,
Residue
Chemistry
Reregistration
Branch
II
Health
Effects
Division
(
HED)

THROUGH:
Alan
Nielsen,
Branch
Senior
Scientist
Reregistration
Branch
II
Health
Effects
Division
(
HED)

TO:
John
Pates,
Jr.,
Chemical
Review
Manager
Reregistration
Branch
Special
Review
and
Reregistration
Division
(
7508C)
Page
2
of
105
The
following
human
health
risk
assessment
for
triadimefon
has
been
prepared
by
the
Health
Effects
Division
as
part
of
the
Reregistration
Eligibility
Decision
(
RED)
process.
This
assessment
has
been
reviewed
by
the
HED
Risk
Assessment
Review
Committee
(
RARC)
on
November
3,
2005.
At
this
meeting,
all
aspects
of
the
Human
Health
risk
assessment
were
concurred
on,
including
toxicological
endpoints
and
dose
levels
for
risk
assessment,
exposure
estimates
for
food
and
drinking
water,
residential
exposure
estimates,
and
exposure
estimates
for
professional
applicators.
The
following
risk
assessment
has
been
revised
in
response
to
Risk
Assessment
Review
Committee
comments.

Triadimenol
It
is
important
to
note
that
the
primary
metabolite
of
triadimefon
(
PC
109901)
is
triadimenol,
and
triadimenol
is
registered
separately
under
its
own
active
ingredient
identity
number
(
PC
127201).
Triadimenol,
used
exclusively
in
the
U.
S.
as
a
seed
treatment
for
cotton
and
grains,
is
also
being
assessed
by
the
Agency
for
the
purposes
of
tolerance
reassessment
eligibility
(
TRED).
In
an
instance
such
as
this,
it
is
usually
considered
appropriate
to
aggregate
the
estimated
exposure
of
the
two
separate
sources.
Final
aggregation,
however,
is
being
deferred
due
to
the
significant
risk
issues
found
in
the
triadimefon­
only
risk
assessment
presented
here.

Supporting
Documents
Tier
2
Drinking
Water
Assessment
for
Triadimefon
and
its
Major
Degradate
Triadimenol
(
J.
Angier
memo,
8/
31/
05)

Review
of
Triadimefon
Incident
Reports
(
M.
Hawkins
memo,
8/
24/
05)

Usage/
Use
Report/
Package
in
Support
of
Reregistration
for
the
Fungicide
Triadimefon
(
J.
Carter
memo,
6/
7/
05)

Triadimefon.
Summary
of
Analytical
Chemistry
and
Residue
Data
for
the
Reregistration
Eligibility
Decision
(
RED)
Document
(
S.
Ary
memo,
11/
23/
05)

Triadimefon.
Acute
and
Chronic
Dietary
Exposure
Assessments
for
the
Reregistration
Eligibility
Decision
(
RED)
Document
(
S.
Ary
memo,
11/
23/
05)

Triadimefon:
Occupational
and
Residential
Exposure
Assessment
for
the
Reregistration
Eligibility
Decision
Document
(
S.
Recore
memo,
10/
13/
05)

Triadimefon:
Summary
of
Product
Chemistry
Data
for
Reregistration
Eligibility
Decision
(
RED)
Document
(
P.
Y.
Barnes
memo,
11/
22/
05)
Page
3
of
105
CONTENTS
Pg
1.0
Summary
5
2.0
Use
/
Structure
/
Properties
Profile
10
2.1
Uses
/
Products
10
2.2
Use
Patterns
/
Rates
11
2.3
Percent
Treatment
11
2.4
Structure
/
Properties
12
3.0
Metabolism
Assessment
13
3.1
Metabolism
in
the
Rat
13
3.2
Metabolism
in
Plants
14
3.3
Metabolism
in
Livestock
15
3.4
Metabolim
in
Rotational
Crops
15
3.5
Metabolism
in
the
Environment
16
3.6
Tabular
Summary
of
Metabolites/
Degradates
18
4.0
Hazard
Characterization
/
Assessment
20
4.1
Hazard
Profile
20
4.1.1
Available
Studies
20
4.1.2
Evidence
of
Neurotoxicity
20
4.1.3
Toxicological
Effects
21
4.1.4
Dose
Response
22
4.2
FQPA
Considerations
33
4.2.1
Adequacy
of
the
Toxicity
Data
Base
33
4.2.2
Developmental
Toxicity
33
4.2.3
Reproductive
Toxicity
34
4.2.4
Pre­
and/
or
Postnatal
Toxicity
37
4.2.5
Recommendation
for
a
DNT
Study
37
4.3
Special
FQPA
Safety
Factor
37
4.4
Hazard
Identification
and
Toxicity
Endpoint
Selection
38
4.4.1
Acute
Reference
Dose
(
aRfD)
38
4.4.2
Chronic
Reference
Dose
(
cRfD)
39
4.4.3
Incidental
Oral
Exposure
(
Short­,
Intermediate­
Term)
39
4.4.4
Dermal
Exposure
(
Short­,
Intermediate­
Term)
40
4.4.5
Inhalation
Exposure
(
Short­,
Intermediate
­
Term)
40
4.4.6
Margins
of
Exposure
41
4.4.7
Recommendation
for
Aggregate
Risk
Assessment
41
4.4.8
Classification
of
Carcinogenic
Potential
41
4.5
Endocrine
Disruption
43
5.0
Dietary
Exposure
/
Assessment
44
Page
4
of
105
5.1
Tolerances
/
Tolerance
Expression
44
5.2
Analytical
Methods
44
5.3
Field
Trial
Residue
Data
45
5.4
Residue
in
Processed
Commodities
45
5.5
Residue
in
Rotational
Crops
46
5.6
Tolerance
Summary
46
5.7
Residue
in
Drinking
Water
49
5.71
Surface
Water
49
5.72
Groundwater
51
6.0
Residential
Exposure
/
Assessment
55
6.1
Residential
Applicator
Exposure
/
Risk
55
6.2
Residential
Postapplication
Exposure
/
Risk
63
7.0
Aggregate
Risk
Assessment
66
7.1
Spray
Drift
66
7.2
Risk
Estimates
67
8.0
Cumulative
Risk
Assessment
67
9.0
Occupational
Exposure
/
Risk
68
9.1
Occupational
Handler
Overview
68
9.2
Application
Descriptions
69
9.3
Exposure
Duration
70
9.4
Exposure
Scenario
Summary
70
9.5
Application
Rates
72
9.6
Occupational
Handler
Risk
Estimates
73
9.7
Occupational
Handler
Risk
Summary
91
9.8
Occupational
Postapplication
Exposure
/
Risk
91
9.9
Occupational
Postapplication
Risk
Estimates
94
10.0
Postapplication
Risk
Summary
95
10.0
Human
Incident
Data
Review
96
11.0
Data
Requirements
98
Appendices
99
1.0
Toxicology
Data
Summary
99
2.0
Product
Chemistry
Data
Summary
100
Page
5
of
105
1.0
SUMMARY
Triadimefon
[
1­(
4­
chlorophenoxy)­
3,3­
dimethyl­
1­(
1H­
1,2,4­
triazol­
1­
yl)­
2­
butanone]
is
a
systemic
fungicide
used
to
control
rust
and
mildew
on
apples,
grapes,
pears,
pineapple,
and
raspberries.
Non­
food
uses
include
pine
seedlings,
Christmas
trees,
residential
and
commercial
turf,
ornamentals,
and
landscapes.
Triadimefon
end­
use
products
are
marketed
in
the
United
States
under
the
trade
name
Bayleton
®
and
Summit
®
.
The
reregistration
of
triadimefon
is
being
supported
by
the
basic
producer,
Bayer
Corporation.

The
Agency
has
determined
that
the
residues
of
concern
(
for
risk
assessment)
in
plants
and
livestock
are
triadimefon,
triadimenol
[$­(
4­
chlorophenoxy)­"­(
1,1­
dimethylethyl)­
1H­
1,2,4­
triazole­
1­
ethanol],
1­(
4­
chlorophenoxy)­
3,3­
dimethyl­
3­
hydroxymethyl­
1­(
1H­
1,2,4­
triazol­
1­
yl)­
2­
butanone
(
KWG
1323),
and
1­(
4­
chlorophenoxy)­
3,3­
dimethyl­
3­
hydroxymethyl­
1­(
1H­
1,2,4­
triazol­
1­
yl)­
2­
butanol
(
KWG
1342)..
Based
on
an
analysis
of
the
structural
relationship
of
the
above
metabolites
to
parent
triadimefon,
the
toxicity
of
metabolites
is
not
expected
to
exceed
the
parent
compound,
and
an
assumption
of
equal
toxicity
is
made
for
aggregate
risk
assessment.

This
risk
assessment
does
not
specifically
address
the
metabolites;
1,2,4­
triazole
and
two
conjugates,
triazole
alanine
and
triazole
acetic
acid.
These
three
metabolites
are
common
to
most
of
the
triazole
fungicides.
Although
the
Agency
is
currently
assessing
these
metabolites,
no
final
conclusions
or
recommendations
have
been
made.

The
toxicological
database
contained
acceptable/
guideline
studies
including
acute
and
subchronic
neurotoxicity,
developmental,
chronic,
carcinogenicity,
combined
chronic
/
carcinogenicity,
and
subchronic
dermal
studies.
The
toxicological
database
also
contained
acceptable/
nonguideline
reproduction
studies.
The
database
is
also
supported
by
substantial
data,
including
some
studies
performed
by
EPA
scientists,
from
the
literature
that
supports
the
mode
of
toxic
action
and
endpoint
selection.
For
the
purposes
of
reregistration,
the
database
is
adequate
although
there
are
data
gaps
(
lack
of
developmental
neurotoxicity
and
an
inhalation
study).

Triadimefon
is
known
to
cause
neurotoxic
effects.
Acute
neurotoxic
signs
observed
in
mice,
rats,
and
rabbits
consisted
of
"
apathy,
labored
breathing,
increased/
decrease
mobility,
staggering
and
cramped
posture,
aggressiveness,
and
self­
mutilation."
Hyperactivity,
biting,
and
antagonism
behavior
has
been
observed
in
rats,
and
the
durations
of
these
effects
were
dose­
related.
The
mode
of
toxic
action
for
triadimefon
involves
blocking
the
reuptake
of
dopamine.
These
pesticides
act
as
indirect
dopamine
agonists
by
binding
to
the
dopamine
transporter
and
increasing
levels
of
synaptic
dopamine.
The
toxicological
impact
of
blocking
this
reuptake
following
exposure
to
triadimefon
during
development
is
not
know.
A
developmental
neurotoxicity
study
with
triadimefon
is
required
at
this
time.

There
was
no
evidence
for
quantitative
and
qualitative
susceptibility
following
oral
exposures
to
rats
in
utero.
However,
there
was
an
increase
susceptibility
following
oral
exposure
to
rabbits
in
utero.
The
degree
of
concern
for
pre­
and/
or
post­
natal
susceptibility
is
low
because
the
rabbit
Page
6
of
105
NOAEL
(
20
mg/
kg/
day)
is
adequate
due
to
dose
spacing.
The
endpoint
used
for
risk
assessment
purposes
(
NOAEL
of
3.4
mg/
kg/
day
from
the
subchronic
neurotoxicity
study)
is
10x
lower
than
the
rabbit
NOAEL
and
it
is
accounted
for
in
the
overall
FQPA
database
uncertainty
factor
10x
for
the
lack
of
a
DNT.

Based
on
the
submitted
data,
the
special
FQPA
safety
factor
of
10x
is
not
required
since
the
current
developmental
and
reproductive
toxicity
studies
do
not
suggest
that
the
young
are
more
sensitive
than
adult
animals,
and
the
lack
of
DNT
is
addressed
by
the
FQPA
database
uncertainty
factor
of
10x.
Therefore,
the
FQPA
Safety
Factor
is
1.

Although
an
acceptable
acute
neurotoxicity
study
(
ACN)
is
available,
the
subchronic
neurotoxicity
study
(
SCN)
was
used
to
establish
the
acute
reference
dose
(
aRfD).
The
endpoint
of
concern
is
neurotoxicity
seen
after
both
an
acute
gavage
study
and
after
repeated
dietary
exposure.
The
LOAEL
for
neurotoxicity
was
54.6%
and
68.7&
mg/
kg/
day,
based
primarily
on
hyperactivity.
The
NOAEL
was
3.4%
and
4.3&
mg/
kg/
day.
For
the
acute
dietary
risk
assessment,
the
total
uncertainty
factor
(
UF)
is;
1,000x
(
10x
for
interspecies
extrapolation,
10x
for
intraspecies
variations,
and
10x
for
the
FQPA
database
uncertainty
(
lack
of
a
developmental
neurotoxicity
study).
Since
there
is
no
special
FQPA
factor
applied,
the
acute
Population
Adjusted
Dose
(
aPAD)
is
0.0034
mg/
kg/
day.

The
subchronic
neurotoxicity
study
in
rats
was
also
chosen
for
the
basis
of
the
chronic
reference
dose
(
cRfD).
The
endpoint
of
concern
is
neurotoxicity
seen
after
both
an
acute
gavage
study
and
after
repeated
dietary
exposure.
Using
the
subchronic
neurotoxicity
study
accounts
for
the
most
sensitive
species
and
endpoints
(
rat
vs.
chronic
dog
study).
The
LOAEL
for
neurotoxicity
was
54.6%
and
68.7&
mg/
kg/
day
based
largely
on
hyperactivity.
The
NOAEL
was
3.4%
and
4.3&
mg/
kg/
day.
For
the
chronic
dietary
risk
assessment,
the
uncertainty
factor
(
UF)
is;
1,000x
(
10x
for
interspecies
extrapolation,
10x
for
intraspecies
variations,
and
10x
for
the
database
uncertainty
(
lack
of
a
developmental
neurotoxicity
study).
Since
there
is
no
special
FQPA
factor
applied,
the
chronic
Population
Adjusted
Dose
(
cPAD)
is
0.0034
mg/
kg/
day.

The
21­
day
dermal
toxicity
study
in
rats
was
chosen
as
the
basis
for
the
risk
assessment
of
shortand
intermediate­
term
dermal
exposure.
The
LOAEL
was
1,000
mg/
kg/
day
based
on
increased
reactivity
and
activity
in
the
females.
The
NOAEL
was
300
mg/
kg/
day.
In
the
absence
of
a
repeated
inhalation
exposure
study,
the
subchronic
neurotoxicity
study
in
rats
was
also
chosen
for
the
assessment
of
short­
and
intermediate­
term
inhalation
exposure.
No
long­
term
exposure
is
expected.

A
Margin
of
Exposure
(
MOE)
of
1,000
is
the
target
level
for
residential
exposure
to
triadimefon;
10x
for
interspecies
extrapolation,
10x
for
intraspecies
variability,
and
10x
for
the
database
uncertainty
(
lack
of
a
DNT
study).
However;
a
Margin
of
Exposure
of
100
is
the
target
level
for
occupational
exposure
to
triadimefon
(
10x
for
interspecies
extrapolation
and
10x
for
intraspecies
variability).
Page
7
of
105
The
HED
Cancer
Assessment
Review
Committee
(
CARC)
classified
triadimefon
into
category
C
"
possible
human
carcinogen."
This
classification
is
based
on
a
statistically
significant
increase
in
thyroid
adenomas
in
male
Wistar
rats
and
statistically
significant
increases
in
hepatocellular
adenomas
in
both
sexes
of
the
NMRI
mouse.
However,
it
was
concluded
that
a
quantified
carcinogenic
risk
assessment
for
triadimefon
is
not
appropriate
and
risk
assessment
will
be
based
on
the
cPAD
and
Margin
of
Exposure
approaches,
only.

Tolerances
are
established
for
residues
of
triadimefon
[
1­(
4­
chlorophenoxy)­
3,3­
dimethyl­
1­(
1H­
1,2,4­
triazol­
1­
yl)­
2­
butanone]
and
its
metabolites
containing
chlorophenoxy
and
triazole
moieties
(
expressed
as
the
parent
compound)
in/
on
various
plant
and
animal
commodities
[
40
CFR
§
180.410].
A
tolerance
with
regional
registration
is
established
for
triadimefon
and
its
metabolites
in
raspberries
at
2.0
ppm
[
40
CFR
§
180.410(
c)].

Data
submitted
for
the
"
magnitude"
(
amount)
of
residue
in/
on
apples,
grapes,
pears,
pineapple,
and
raspberries
(
based
on
current
use
patterns)
are
adequate
for
reregistration.
The
available
crop
field
trials
reflecting
use
of
registered
formulations
at
1x
the
maximum
label
rate
show
finite
residues
of
triadimefon
and
its
metabolites
triadimenol,
KWG
1342,
and
KWG
1323
in/
on
apples,
grapes,
pears,
and
pineapples
and
triadimefon
and
triadimenol
in/
on
raspberries.
Analysis
for
residues
of
the
metabolites
KWG
1342
and
KWG
1323
were
not
performed
in
the
raspberry
field
trials.

Triadimefon
transforms
into
triadimenol
in
the
natural
environment,
particularly
in
shallow
subsurface
soil
and
is
moderately
mobile
and
persistent.
Triadimefon
on
or
near
the
soil
surface
or
on
vegetation
may
be
subject
to
runoff
and/
or
erosion
into
surface
water
bodies
used
as
drinking
water
supplies.
Triadimefon
and
triadimenol
may
also
leach
into
groundwater
when
triadimefon
is
applied
in
areas
with
well­
drained
soil,
high
rainfall
(
and/
or
irrigation)
rates,
and
shallow
water
tables.
Once
it
reaches
groundwater,
triadimenol
is
likely
to
degrade
more
slowly
than
the
parent
compound.

The
(
modeled)
triadimefon
surface
water
assessment
is
based
on
three
crop
scenarios;
use
on
Christmas
trees
in
Oregon,
use
on
apples
in
Pennsylvania,
and
use
on
turf
in
Florida
.
These
scenarios
represent
different
and
characteristic
U.
S.
regions
where
these
crops
are
commonly
grown.
These
particular
scenarios
were
also
chosen
because
they
have
the
highest
labeled
use
rates
and
are
expected
to
present
the
greatest
risk
to
drinking
water
supplies.
Estimates
are
based
on
the
maximum
rate
of
26
application
per
year,
and
for
comparison,
and
the
rate
of
3
applications
per
year.
Ground
water
monitoring
studies
supplied
by
the
registrant
indicate
maximum
concentrations
of
total
triadimefon
residues
are
somewhat
lower
than
predicted
by
SCIGROW
but
nonetheless
of
similar
magnitude.

Based
on
USDA/
PDP,
field
trial,
and
percent
crop
treted
data,
refined
acute
and
chronic
dietary
(
food
and
water)
exposure
assessments
were
conducted
using
the
Dietary
Exposure
Evaluation
Model
software
with
the
Food
Commodity
Intake
Database
(
DEEM­
FCID
 
,
Version
2.03),
which
uses
food
consumption
data
from
the
USDA's
Continuing
Surveys
of
Food
Intakes
by
Page
8
of
105
Individuals
(
CSFII)
from
1994­
1996
and
1998.

Based
on
supported
commodities,
and
assuming
three
applications
per
year
to
turf,
the
acute
dietary
(
food
and
water
sources)
risk
estimates
exceed
HED's
level
of
concern
at
the
99.9th
exposure
percentile
for
the
U.
S.
population
(
230%
of
the
aPAD)
and
all
population
subgroups,
with
the
highest
exposed
population
subgroup
being
all
infants
less
than
one
year
old
at
710%
of
the
aPAD.
The
significant
acute
risk
contributors
have
been
identified
as
water
(
direct
and
indirect,
all
sources),
grape
juice,
pineapple
juice,
and
fresh
grapes.

The
acute
dietary
risk
estimates
for
food
alone
(
no
water)
exceed
HED's
level
of
concern
at
the
99.9th
exposure
percentile
for
children
1­
2
years
old
at
240%
of
the
aPAD,
children
3­
5
years
old
at
170%.
It
is
also
noted
that
the
acute
dietary
risk
estimates
for
either
surface
water
concentrations
(
no
food),
26
applications
or
3
applications,
exceed
HED's
level
of
concern
at
the
99.9th
exposure
percentile
for
the
U.
S.
population
and
all
population
subgroups.

Based
on
supported
commodities,
and
assuming
three
applications
per
year
to
turf,
the
chronic
dietary
(
food
and
water
sources)
risk
estimates
do
not
exceed
HED's
level
of
concern
for
the
U.
S.
population
(
16%
of
the
cPAD)
and
all
population
subgroups,
with
the
highest
exposed
population
subgroup
being
all
infants
less
than
one
year
old
at
52%
of
the
cPAD.

The
chronic
dietary
risk
estimates
for
the
surface
water
concentration
(
no
food)
that
was
generated
using
26
applications
exceed
HED's
level
of
concern
for
all
infants
less
than
one
year
old
at
300%
of
the
cPAD,
children
1­
2
years
old
at
140%
of
the
cPAD,
and
children
3­
5
years
old
at
130%
of
the
cPAD.

Triadimefon
products
are
marketed
for
homeowner
use
on
residential
lawns,
landscape
ornamentals,
trees,
fruit
trees,
and
grapes.
Risk
estimates
for
the
homeowner­
applicator
are
based
on
both
dermal
and
inhalation
exposure,
with
the
likely
durations
of
short­
and
intermediate­
term.
Residential
applicator
exposure
is
less
than
the
target
Margin
of
Exposure
(
MOE)
of
1,000
for
only
one
exposure
scenario,
mixing/
loading
/
applying
liquid
concentrates
with
a
hose­
end
sprayer
to
residential
turf
(
MOE
=
500).

Triadimefon­
containing
products
are
also
marketed
for
use
by
professional
applicators
(
Pest
Control
Operators,
or
PCOs)
on
residential
turf,
on
golf
courses,
other
turf
such
as
recreational/
commercial
areas,
and
on
ornamental
plantings.
These
uses
are
assessed
for
post­
application
exposure
and
are
based
on
dermal
exposure,
only,
with
exposure
durations
of
short­
and
intermediate­
term.

For
the
residential
postapplication
adult
exposure
scenarios,
short­
term
dermal
MOEs
are
<
1,000
on
the
day
of
application
for
turf/
high
contact
activities
of
mowing
and
gardening.
Shortterm
MOE
estimates
for
youths
were
<
1,000
for
all
exposure
scenarios
except
golfing.
Risk
estimates
for
toddlers
were
calculated
for
postapplication
exposure
following
the
application
of
triadimefon
to
residential
turf.
Short­
term
MOE
estimates
for
toddlers
were
<
1,000
for
the
Page
9
of
105
residential
turf
/
high
contact
activities;
hand­
to­
mouth
activities,
object­
to­
mouth
activities,
and
the
"
incidental"
ingestion
of
granules/
pellets.

Aggregate
risk
considerations,
combining
the
estimated
exposure
from
dietary
(
food
and
drinking
water
sources),
have
been
deferred
at
this
time
since
the
risk
estimates
for
dietary
exposure
alone
are
significantly
greater
than
the
dose
levels
selected
for
risk
assessment.
Risk
estimates
based
on
residential
turf
use
are
also
significantly
greater
than
the
target
maximum
exposure
level.

Occupational
risk
is
assessed
for
exposure
at
the
time
of
application
and
assessed
for
exposure
following
application,
or
postapplication
exposure.
Occupational
risk
estimates
are
expressed
as
MOEs,
and
are
determined
by
a
comparison
of
specific
exposure
scenario
estimates
to
the
dose
level
(
NOAEL)
of
300
mg/
kg/
day
for
short­
and
intermediate­
term
dermal
assessment,
and
3.4
mg/
kg/
day
for
short­
and
intermediate­
term
inhalation
assessment.
For
professional
triadimefon
users
the
Agency
has
established
a
"
target"
MOE
of
100
for
both
short­
and
intermediate­
term
exposure.
Long­
term
worker
exposure
is
not
expected
or
assessed
for
triadimefon.

For
the
scenarios
that
do
not
involve
seed
treatment,
all
handler
exposure
scenarios,
except
one,
the
dermal
and
inhalation
risk
estimates
met
(
or
exceeded)
the
target
MOE
level
of
100
at
some
level
of
risk
mitigation.
Based
on
PHED
data,
the
estimated
inhalation
risk
for
the
following
scenario
remains
a
concern
with
maximum
inhalation
risk
mitigation:
mixng/
loading/
applying
wettable
powders
with
a
low
pressure
handwand
to
turf
(
the
dermal
MOE
=
110
with
double
layer
and
gloves;
however
the
inhalation
MOE
=
80
with
a
90%
protection
factor
half­
face
respirator).
The
combined
dermal
and
inhalation
risk
estimate
for
this
scenario
has
an
MOE
of
46
with
a
double
layer,
gloves,
and
a
90%
protection
factor
half­
face
respirator.

In
all
nursery
seed­
treatment
scenarios,
dermal
and
inhalation
MOEs
met
or
exceeded
the
target
MOE
of
100
at
some
level
of
risk
mitigation.
In
all
nursery
seed­
treatment
scenarios,
combined
dermal
and
inhalation
MOEs
met
or
exceeded
the
target
MOE
of
100
at
some
level
of
risk
mitigation.

For
commercial
seed
treatment,
all
dermal
MOEs
met
or
exceeded
the
the
target
MOE
of
100
at
some
level
of
mitigation.
However,
inhalation
exposure
remains
a
concern
for
two
scenarios
(
even
with
maximum
inhalation
risk
mitigation):
1)
loader/
applicator
for
ponderosa
pine
seed,
where
inhalation
MOE
=
43
with
engineering
controls);
and
2)
multiple
activities
for
ponderosa
pine
seed,
where
inhalation
MOE
=
92
with
a
90%
protection
factor
half­
face
respirator.
For
these
two
scenarios,
the
combined
dermal
and
inhalation
MOEs
are
43
and
92
respectively.

The
occupational
postapplication
exposure
and
risk
assessment
for
agricultural
crop
uses
of
triadimefon
indicates
that
the
target
MOE
of
100
is
met
or
exceeded
at
day
0
(
i.
e.,
12
hours
after
application)
for
all
crops
and
all
postapplication
activities.

Both
California
and
Poison
Control
Center
data
show
a
clear
pattern
of
irritative,
but
usually
minor
symptoms
from
exposure
to
triadimefon.
Irritation
to
skin,
eyes,
and
respiratory
passage
Page
10
of
105
occurs
readily
among
unprotected
handlers
(
applicators
and
mixer/
loaders)
and
among
those
who
have
substantial
contact
with
foliage
such
as
grape
harvesters
and
tenders.
It
was
unclear
whether
triadimefon
might
also
be
a
sensitizer,
contributing
to
allergic­
type
reactions.
Page
11
of
105
2.0
USE
/
STRUCTURE
/
PROPERTIES
2.1
Registered
Uses
/
Products
Triadimefon
[
1­(
4­
chlorophenoxy)­
3,3­
dimethyl­
1­(
1H­
1,2,4­
triazol­
1­
yl)­
2­
butanone]
is
a
systemic
fungicide
used
to
control
rust
and
mildew
on
apples,
grapes,
pears,
pineapple,
and
raspberries.
Non­
food
uses
include
pine
seedlings,
Christmas
trees,
residential
and
commercial
turf,
ornamentals,
and
landscapes.
Triadimefon
end­
use
products
are
marketed
in
the
United
States
under
the
trade
names
Bayleton
®
and
Summit
®
.
The
reregistration
of
triadimefon
is
being
supported
by
the
basic
producer,
Bayer
Corporation.

Bayer
CropScience
Triadimefon
Product
Registrations
264­
736
Bayleton
®
Technical
Fungicide
264­
737
Bayleton
®
50%
Wettable
Powder
264­
740
Bayleton
®
50%
Concentrate
Fungicide
432­
1293
Bayleton
®
25%
Wettable
Powder
432­
1294
Bayleton
®
50%
Wettable
Powder
Fungicide
in
Water
Soluble
Packets
432­
1295
Bayleton
®
1%
Granular
Turf
Fungicide
432­
1296
Bayleton
®
0.5%
Granular
Turf
Fungicide
432­
1297
Bayleton
®
009
EC
Turf
and
Ornamental
Fungicide
432­
1300
Bayleton
®
216
Concentrate
432­
1309
Bayleton
®
25
Turf
and
Ornamental
Systemic
Fungicide
in
Water
Soluble
Packets
432­
1316
Bayleton
®
25
Wettable
Powder
Nursery
and
Greenhouse
Systemic
Fungicide
432­
1317
Bayleton
®
25
Nursery
and
Greenhouse
Systemic
Fungicide
in
Water
Soluble
Packets
432­
1336
Bayleton
®
1%
Granular
Turf
and
Sod
Production
Fungicide
432­
1360
Bayleton
®
50
Turf
and
Ornamental
Fungicide
in
Water
Soluble
Packets
432­
1367
Bayleton
®
50
WDG
Nursery
and
Greenhouse
Systemic
Fungicide
72155­
46
Bayleton
®
1Granular
Fungicide
72155­
47
Bayleton
®
Granular
Fungicide
72155­
48
Bayleton
®
Liquid
Concentrate
Fungicide
OR­
04­
0016
Bayleton
®
50%
Wettable
Powder
Page
12
of
105
2.2
Use
Patterns
/
Rates
Triadimefon
is
used
as
a
preharvest
foliar
treatment
on
apples
and
pears,
up
to
12
times
per
season,
at
a
maximum
annual
rate
of
0.75
lbs
active
ingredient
(
ai)
/
acre
(
A).
Triadimefon
is
used
as
a
preharvest
foliar
treatment
on
grapes,
up
to
6
times
per
season,
at
a
maximum
annual
rate
of
0.56
lbs
ai/
A.
Triadimefon
is
used
as
a
preharvest
foliar
treatment
on
raspberries,
up
to
7
times
per
season,
at
a
maximum
annual
rate
of
0.88
lbs
ai/
A.

Triadimefon
is
used
as
a
preharvest
foliar
treatment
on
Christmas
trees,
up
to
8
times
per
season,
at
a
maximum
annual
rate
of
2.0
lbs
ai/
A.
Triadimefon
is
used
as
a
preharvest
foliar
treatment
on
pine
seedlings,
up
to
16
times
per
season,
at
a
maximum
annual
rate
of
2.0
lbs
ai/
A.
For
pineapple,
triadimefon
is
applied
as
a
dip
at
a
maximum
rate
of
0.28
lbs
ai/
100
gallons
solution,
and
is
applied
as
a
dip
or
spray
to
the
whole
fruit
following
harvest,
at
a
maximum
rate
of
0.28
lbs
ai/
100
gallons
solution.
Triadimefon
is
also
used
as
a
pine
seed
soak
(
0.63
lbs
ai/
100
gal
solution),
and
as
a
pine
seed
treatment
(
0.063
lbs
ai/
100
gal
solution),
one
time
prior
to
planting.

2.3
Percent
Treatment
of
Registered
Crops
Screening
level
estimates
of
triadimefon
use
in
the
U.
S.,
based
on
data
from
the
years
1990
through
2000,
have
been
provided
by
the
OPP/
Biological
and
Economic
Analysis
Division
(
J.
Carter
and
J.
O'Neill
memo,
6/
7/
05).
Total
use
averaged
135,000
lbs
ai
/
year
with
an
upper­
end
estimate
of
266,000
lbs
ai
/
year.
The
largest
market,
in
terms
of
total
pounds
ai,
was
seen
in
the
turf
and
ornamental
sector
(
74%
of
total
usage).
Estimates
of
the
percent
of
total
acres
treated,
for
the
registrant
­
supported
food
commodities,
are:

Crop
Average
Maximum
Raspberries
50%
N/
A
Apples
5%
10%
Pears
5%
5%
Grapes
<
1%
5%
Pineapple
N/
A
N/
A
Page
13
of
105
O
N
N
N
Cl
O
C(
CH
3
)
3
2.4
Structure
/
Physicochemical
Properties
Triadimefon:

[
1­(
4­
chlorophenoxy)­
3,3­
dimethyl­
1­(
1H­
1,2,4­
triazol­
1­
yl)­
2­
butanone]

Table
2.1
Triadimefon
Nomenclature
Common
name
Triadimefon
Molecular
formula
C14H16ClN3O2
Molecular
weight
293.75
g/
mol
IUPAC
name
(
RS)­
1­(
4­
chlorophenoxy)­
3,3­
dimethyl­
1­(
1H­
1,2,4­
triazol­
1­
yl)­
butan­
2­
one
CAS
name
1­(
4­
chlorophenoxy)­
3,3­
dimethyl­
1­(
1H­
1,2,4­
triazol­
1­
yl)­
2­
butanone
CAS
number
43121­
43­
3
PC
Code
109901
Current
food/
feed
site
registration
apple,
grape,
pear,
pineapple,
and
raspberry
Table
2.2
Physicochemical
Properties
of
Triadimefon
Parameter
Value
Reference
Melting
point/
range
82.3
°
C
MRID
41616001
pH
5.5
in
a
1%
suspension
compared
to
water
MRID
41616001
Density
at
20
°
C
1.23
g/
mL
at
20
°
C
MRID
41616001
Water
solubility
at
25
°
C
64
mg/
L
at
20
°
C
MRID
41616001
Solvent
solubility
at
25
°
C
Moderately
soluble
in
most
organic
solvents
except
aliphatics
MRID
41616001
Vapor
pressure
at
25
°
C
0.2
mPa
at
20
°
C
MRID
42307801
0.6
mPa
at
25
°
C
Dissociation
constant,
pKa
Not
available
Octanol/
water
partition
coefficient
log
Po/
w
of
3.11
at
22
°
C
MRID
42307801
UV/
visible
absorption
spectrum
Not
available
Page
14
of
105
3.0
METABOLISM
ASSESSMENT
The
metabolism,
or
degradation
of
triadimefon
has
been
studied
in
the
rat,
in
plants,
in
livestock,
and
in
the
environment.
It
should
be
noted
that,
except
for
1,2,4­
triazole,
specific
toxicological
data
are
not
available
for
the
other
triadimefon
metabolites
(
KWG
1323,
KWG
1342,
and
KWG
1732
[
1­(
4­
chlorophenoxy)­
1­(
1H­
1,2,4­
triazol­
1­
yl)
ethanoic
acid])
identified
in
metabolism
studies.
However,
based
on
an
analysis
of
the
structural
relationship
of
the
above
metabolites
to
parent
triadimefon,
the
toxicity
of
metabolites
is
not
expected
to
exceed
the
parent
compound,
and
an
assumption
of
equal
toxicity
is
made
for
aggregate
risk
assessment.
The
metabolite,
1,2,4­
triazole,
occurs
in
other
triazole
pesticides
and
a
risk
assessment
specific
to
1,2,4,­
triazole
is
currently
being
conducted
by
the
Agency.

3.1
Metabolism
in
the
Rat
In
a
rat
metabolism
study,
[
14C]
triadimefon
in
50%
aqueous
ethanol
was
administered
as
a
single
gavage
dose
at
24.5­
25.0
mg/
kg
to
12
Sprague
Dawley
rats/
sex
to
determine
tissue
distribution
and
to
12
rats/
sex
to
determine
the
excretion
profile.
Radioactivity
was
not
detected
in
the
expired
air
of
animals.
Over
a
7
day­
period,
recovery
in
urine
was
29.8%
dose
in
males
and
39.9%
in
females,
and
recovery
in
feces
was
52.7%
in
males
and
34.5%
in
females.
Thus,
based
on
urinary
excretion,
absorption
was
at
least
29.8%
dose
in
all
animals.
Plasma
levels
of
radioactivity
were
highest
1­
2
hours
post­
dose
(
2.5­
3.2
ppm),
and
the
half­
life
was
approximately
4
hours.
Tissue
concentrations
in
males
were
generally
similar
to
females.
The
highest
concentrations
of
radioactivity
were
found
in
fat
(
43.5­
45.0
ppm)
at
4­
8
hours
post­
dose.
Approximately
50%
of
the
radiolabeled
compound
in
the
fat
of
males
was
unchanged
triadimefon
and
50%
was
isomeric
forms
of
the
2­
butanol
derivative
(
triadimenol);
over
90%
was
triadimefon
in
females.
In
addition,
relatively
high
concentrations
of
radioactivity
were
observed
in
the
liver
(
26.2­
28.4
ppm)
and
skin
(
21­
22
ppm)
at
2
hours
post­
dose.
Tissue
concentrations
were
<
0.14
ppm
at
7
days
post­
dose.
In
the
urine,
the
major
component
of
the
acidified
extract
was
KWG
0519
(
triadimenol)
acid
(
6.1­
7.7%
dose).
In
the
direct
extract
of
urine,
3
minor
metabolites
were
identified:
p­
chlorophenol,
KWG
1323,
and
KWG
1342
(
two
isomers).
In
the
direct
extract
of
the
feces,
KWG
1323,
KWG
1342,
and
KWG
0519
acid
(
5.7­
20.0%
dose)
were
identified.
KWG
1323
was
the
predominant
metabolite
in
the
feces
of
females
(
12.7%
dose),
and
KWG
0519
acid
was
the
predominant
metabolite
in
the
feces
of
males
(
20.0%
dose).
Thus,
the
major
metabolites
were
the
alcohol
and
acid
of
triadimefon,
which
were
formed
by
the
sequential
hydroxylation
and
oxidation
of
the
methyl
group
of
the
t­
butyl
chain.

In
a
second
rat
metabolism
study,
[
14C]
triadimefon
(
99.3%
radiochemical
purity)
in
polyethylene
glycol
was
administered
to
5
Wistar
rats/
sex/
dose
as
a
single
gavage
dose
at
5
or
50
mg/
kg
or
as
a
single
gavage
dose
at
5
mg/
kg
following
14
daily
doses
of
unlabeled
triadimefon
at
5
mg/
kg.
In
addition,
triadimefon
was
administered
to
a
group
3
of
male
rats
as
a
single
gavage
dose
of
50
mg/
kg
in
a
preliminary
study.
Radioactivity
was
not
detected
in
the
expired
air.
The
overall
recovery
of
radioactivity
was
97­
112%.
The
compound
was
predominantly
excreted
(
90­
98%
dose)
within
4
days.
The
excretion
profile
of
the
repeated
low­
dose
group
was
similar
to
the
Page
15
of
105
single
low­
dose
group;
however,
the
excretion
profiles
were
sex­
dependent.
Over
a
4
day­
period,
recovery
in
the
urine
was
24­
28%
dose
in
males
and
57­
66%
in
females,
and
recovery
in
feces
was
63­
66%
in
males
and
32­
40%
in
females.
Thus,
based
on
urinary
excretion,
absorption
was
at
least
24%
dose
in
males
and
57%
in
females.
Less
than
1%
dose
remained
in
the
body
4
days
after
treatment.
Bioaccumulation
was
not
indicated.
Tissue
residues
were
highest
in
the
liver
(
0.088­
1.94
ppm)
and
kidney
(
0.041­
0.38
ppm),
and
were
generally
slightly
higher
in
males
than
in
females.
RP­
HPLC
analyses
revealed
the
presence
of
15
radioactive
components
in
the
urine
and
12
in
the
feces.
The
4
major
metabolites
(
1­
14%
dose,
each)
in
the
urine
of
both
sexes
were:
KWG
0519
acid
(
2
isomers),
KWG
1323­
gluc,
HO­
DeME­
KWG
1342
(
2
isomers),
and
DeMe­
KWG
132­
gluc
(
2
isomers).
The
5
major
metabolites
(
1­
15%
dose,
each)
in
the
feces
of
both
sexes
were:
KWG
0519
acid
(
2
isomers),
KWG
1323­
gluc,
KWG
1323,
KWG
1342,
and
KWG
0519
dehydrate.
Thus,
metabolism
of
this
compound
proceeded
along
several
pathways,
such
as:
(
i)
hydroxylation
at
the
t­
butyl
moiety
and
oxidation
to
the
acid
or
glucuronidation;
(
ii)
reduction
of
the
keto
group
and
subsequent
reactions
(
including
sulfate
conjugation);
and
(
iii)
desmethylation
followed
by
glucuronidation.

3.2
Metabolism
in
Plants
Plant
metabolism
studies
with
triadimefon
have
been
conducted
with
grapes,
cucumbers,
tomatoes,
and
wheat.
In
the
cucumber
and
tomato
metabolism
studies,
seedlings
were
treated
with
[
phenyl­
14C]
triadimefon
at
­

1x
the
maximum
rate
for
cucumbers.
Selected
plants
were
treated
two
additional
times,
beginning
at
fruit
set.
The
metabolism
of
triadimefon
in
tomato
and
cucumber
seedlings
receiving
a
single
foliar
application
appears
to
consist
of
rapid
degradation
of
the
parent
with
a
corresponding
increase
in
triadimenol.

Hydrolysis
of
water­
soluble
radiocarbon
and
foliage
samples
from
cucumber
seedlings
released
triadimefon
and
triadimenol,
as
well
as
low
levels
of
the
metabolites
designated
as
KWG
1323
and
KWG
1342,
which
were
not
detected
in
tomato
seedlings.
Degradation
of
triadimefon
in
mature
cucumber
and
tomato
plants
appeared
to
be
similar
to
that
in
seedlings,
with
minor
differences.
The
fruit
and
foliage
differed
in
their
ability
to
metabolize
the
parent.
In
both
tomato
and
cucumber
fruit,
the
terminal
degradation
product
was
primarily
triadimenol,
while
the
foliage
of
both
tomato
and
cucumber
exhibited
a
more
complex
series
of
degradation
products.

In
a
grape
metabolism
study,
mature
fruit
were
harvested
56
days
following
treatment
of
an
established
vine
with
[
phenyl­
14C]
triadimefon;
immature
fruit
were
harvested
at
various
earlier
intervals.
A
rapid
decline
in
total
radioactivity
was
observed,
due
to
the
volatility
of
triadimefon.
The
decline
in
the
quantity
of
parent
observed
was
accompanied
by
a
buildup
of
the
metabolite
triadimenol.
Triadimenol
accounted
for
56%
of
total
radioactive
residue
(
TRR)
in
mature
grapes
while
triadimefon
was
detected
at
1%
TRR.
The
remainder
of
the
identified
radioactivity
was
comprised
of
KWG
1342
and
its
conjugates
(
16%
TRR),
triadimenol
conjugates
(
6%
TRR),
and
p­
chlorophenol
and
its
conjugates
(
6%
TRR).

Following
treatment
of
wheat
with
[
phenyl­
14C]
triadimefon
at
2x
the
maximum
application
rate,
Page
16
of
105
the
metabolite
KWG
1732
was
the
major
residue
identified
(
35%
TRR)
in
wheat
grain;
a
glucoside
of
KWG
1342
was
the
other
major
residue
identified
(
21%
TRR)
in
wheat
grain.
In
wheat
forage,
triadimefon
and
triadimenol
together
accounted
for
the
majority
of
residues
(
66­
86%
TRR);
p­
chlorophenol
and
its
glucoside
were
also
identified,
at
9­
16%
TRR.
In
wheat
straw,
triadimenol
and
its
conjugates
accounted
for
the
majority
of
the
radioactivity
(
53%
TRR);
p­
chlorophenol
and
its
conjugates
and
KWG
1342
and
its
conjugates
were
also
identified,
at
21%
and
19%
TRR,
respectively.

The
Agency
has
determined
that
the
triadimefon
residues
of
concern
in/
on
apples,
grapes,
pears,
pineapples,
and
raspberries
for
risk
assessment
are
triadimefon,
triadimenol,
KWG
1323,
and
KWG
1342.

3.3
Metabolism
in
Livestock
The
metabolism
of
triadimefon
in
livestock
is
adequately
understood
based
on
studies
conducted
with
goats
(
ruminants)
and
poultry.
In
the
ruminant
study,
a
lactating
goat
was
fed
[
phenyl­
14C]
triadimefon
at
86
ppm
for
three
consecutive
days.
The
parent
was
detected
at
low
levels
in
milk
and
fat
(<
5%
TRR)
but
was
not
detected
in
kidney,
liver,
or
muscle.
The
major
residue
identified
was
KWG
1342
glucuronide
(
6­
47%
TRR).
Triadimenol
and
its
conjugates
comprised
a
major
portion
of
the
residue
in
tissues
and
milk
(
totals
of
9­
42%
TRR).
The
remainder
of
the
radioactivity
was
identified
as
KWG
1323
glucuronide
(
19­
22%
TRR
in
muscle
and
fat)
and
KWG
1342
(
1­
6%
TRR)
and
its
sulfate
(
1­
15%
TRR
in
tissues,
43%
TRR
in
milk).

In
the
poultry
study,
16
laying
hens
were
fed
[
phenyl­
14C]
triadimefon
at
29
ppm
for
three
consecutive
days.
The
parent
was
identified
in
fat
and
eggs
(
4­
17%
TRR)
but
was
not
detected
in
liver
or
muscle.
Triadimenol
and
its
related
compounds
were
the
major
metabolites
identified
(
totals
of
41­
49%
TRR).
The
remainder
of
the
radioactivity
was
identified
as
KWG
1342
and
its
related
compounds
(
totals
of
10­
36%
TRR),
p­
chlorophenol
(
liver
and
fat
at
2­
4%
TRR),
chlorophenoxytriazolyl
acetic
acid
(
muscle
at
3%
TRR),
and
KWG
1323
(
fat
and
eggs
at
3­
5%
TRR).
(
Note
that
there
are
currently
no
registered
uses
of
triadimefon
on
poultry
feed
items).

The
Agency
has
determined
that
the
residues
of
concern
for
risk
assessment
in
livestock
are
triadimefon,
triadimenol,
KWG
1323,
and
KWG
1342.

3.4
Metabolism
in
Rotational
Crops
Because
triadimefon
and
its
regulated
metabolites
were
identified
at
>
0.01
ppm
in
various
rotational
crops,
at
various
intervals,
limited
and/
or
field
rotational
crop
studies
were
required.
However,
the
registrant
has
since
requested
removal
of
all
rotatable
crop
uses
from
product
labels,
and
no
additional
data
pertaining
to
confined/
field
accumulation
in
rotational
crops
will
be
required.
The
reregistration
requirements
for
confined
rotational
crops
are
fulfilled.
(
See
GLN
860.1200).
Page
17
of
105
3.5
Metabolism
/
Degradation
in
the
Environment
Based
on
the
environmental
fate
data,
the
primary
routes
of
triadimefon
degradation
appear
to
be
microbial
and
photolytic
activity.
Previously
submitted
studies
indicate
that
triadimefon
is
less
volatile
than
water,
moderately
soluble
(
71
ppm),
stable
to
hydrolysis
(<
3%
degradation),
but
photolyses
in
water
with
a
half
life
of
7.6
hours.
In
the
aerobic
soil
metabolism
study,
triadimefon
degraded
with
a
half
life
of
5.6
days.
In
the
anaerobic
soil
metabolism
study,
it
had
a
half
life
of
23.1
days.
The
anaerobic
aquatic
metabolism
half
life
was
217
days.
The
field
dissipation
halflives
of
150­
996
days
are
unexpected
since
the
laboratory
half­
lives
are
normally
longer
than
those
in
the
field.
Soil
adsorption
values
for
triadimefon
on
a
variety
of
soils
exceeded
the
"
trigger"
for
ground
water
(
Koc
of
224­
459)
indicating
the
potential
to
leach.
Triadimenol
was
identified
as
the
primary
degradate
in
the
environmental
fate
studies.

Hydrolysis:
Triadimefon
was
relatively
stable
(<
3%
degradation)
in
sterile
aqueous
buffered
solutions
(
pH
5,
7,
and
9)
that
were
incubated
in
darkness
at
25o
C
for
30
days.

Photolysis
in
Water:
Triadimefon
degraded
with
a
half­
life
of
7.6
hours
in
sterile
nonbuffered
water
that
was
continuously
irradiated
using
a
xenon
lamp
at
approximately
25o
C.
Triadimefon
did
not
degrade
in
the
dark
control.
Six
degradates
were
isolated;
however,
only
pchlorophenol
was
conclusively
identified.

Photolysis
on
Soil:
Triadimefon
degraded
with
a
half­
life
of
30
days
(
720
hours
of
irradiation)
on
sandy
loam
soil
that
was
continuously
irradiated
for
15
days
using
a
UV­
filtered
xenon
light
source
at
22­
43
C.
The
only
significant
degradate
in
the
irradiated
soil
was
pchlorophenol

Aerobic
Soil
Metabolism:
Triadimefon
degraded
with
a
half­
life
of
5.6
days
in
sandy
loam
soil
that
was
incubated
aerobically
in
darkness
at
25o
C
and
75%
of
0.33
bar
moisture.
Most
(
83
%)
of
parent
triadimefon
degraded
within
14
days
after
treatment,
and
the
remainder
was
essentially
constant
through
the
end
of
the
study.
Three
major
degradates
identified
were
triadimenol,
4­
chlorophenoxy­
1,2,4­
triazol­
1­
yl­
methane
(
chlorophenoxymethyltriazole;
CPMT),
and
1H­
1,2,4­
triazole.

Anaerobic
Soil
Metabolism:
Triadimefon
degraded
with
a
half­
life
of
23.1
days
in
sandy
loam
soil
that
was
incubated
under
anaerobic
conditions
(
nitrogen
atmosphere)
in
darkness
at
25
oC
and
75%
of
0.33
bar
moisture.
The
major
degradate
identified
was
triadimenol.

Anaerobic
Aquatic
Metabolism:
Triadimefon
degraded
with
a
half­
life
of
217
days
in
a
sediment:
pond
water
system
that
was
incubated
under
anaerobic
conditions
(
nitrogen
atmosphere)
for
up
to
one
year
in
the
dark
at
25o
C.
Triadimefon
that
was
initially
in
the
water
phase
consistently
moved
to
the
soil
phase
of
the
system
by
the
end
of
the
study.
The
only
degradate
identified
was
triadimenol.
Page
18
of
105
Leaching­
Adsorption­
Desorption:
Based
on
column
leaching
studies,
(
aged
30
days)
tridimefon
residues
were
determined
to
be
mobile
in
columns
of
sand
(
3.7%
organic
matter),
sandy
loam
(
1.0%
organic
matter),
silt
loam
(
2.9%
organic
matter)
and
clay
loam
(
2.2%
organic
matter)
soils
that
were
treated
with
triadiemfon
residues
and
leached
with
20
inches
of
0.01
M
calcium
chloride
solution.
At
the
initiation
of
leaching,
parent
tridimefon
was
57%
of
the
aged
residues.
While
triadimefon
and
its
degradate
tridimenol
(
Isomers
I
and
II)
were
only
slightly
mobile
in
the
columns
of
sand
and
silt
loam,
remaining
approximately
in
the
upper
half
of
the
30­
cm
columns,
triadimefon
and
triadimenol
were
mobile
in
the
columns
of
sandy
loam
and
clay
loam.
In
the
columns
of
sandy
loam
and
clay
loam,
triadimefon
and
tridimenol
were
found
throughout
the
columns
and
in
the
leachate.

Terrestrial
Field
Dissipation:
Triadimefon
dissipated
slowly
from
field
plots
located
in
California
planted
to
turfgrass
that
were
treated
once
at
5.44
lb
ai/
A
or
twice
at
2.72
lb
ai/
A/
application
(
total
5.44
lb
ai/
A)
with
triadimefon
(
25%
WP).
The
degradates
identified
were
triadimenol
and
CPMT
(
detected
only
at
the
Fresno
site).
Parent
triadiemfon
was
detected
in
the
18­
24
inch
depth
following
a
single
application
in
both
the
Fresno
and
Watsonville
sites,
and
following
multiple
applications
in
Watsonville.
The
degradate
triadimenol
was
found
at
a
maximum
of
42­
48
inch
depth
following
a
single
application
in
Fresno
and
from
36­
42
inches
following
multiple
applications
in
Fresno
and
Watsonville.
Page
19
of
105
O
N
N
N
Cl
O
C(
CH
3
)
3
O
N
N
N
Cl
C(
CH
3
)
3
O
H
O
N
N
N
Cl
O
CH
3
CH
3
CH
2
OH
O
N
N
N
Cl
O
H
CH
3
CH
3
CH
2
OH
O
N
N
N
Cl
O
OH
Table
3.1:
Triadimefon
Metabolites
/
Degradates
Chemical
Structure
Triadimefon
1­(
4­
chlorophenoxy)­
3,3­
dimethyl­
1­(
1H­
1,2,4­
triazol­
1­
yl)­
2­
butanone
livestock
plants
drinking
water
Triadimenol;
KWG
0519
$­(
4­
chlorophenoxy)­"­(
1,1­
dimethylethyl)­
1H­
1,2,4­
triazole­
1­
ethanol
livestock
plants
drinking
water
KWG
1323
1­(
4­
chlorophenoxy)­
3­
methyl­
3­
hydroxymethyl­
1­(
1H­
1,2,4­
triazol­
1­
yl)­
2­
butanone
livestock
plants
KWG
1342
1­(
4­
chlorophenoxy)­
3­
methyl­
3­
hydroxymethyl­
1­(
1H­
1,2,4­
triazol­
1­
yl)­
2­
butanol
livestock
plants
KWG
1732
1­(
4­
chlorophenoxy)­
3,3­
dimethyl­
1(
1H­
1,2,4­
triazol­
1­
yl)
ethanoic
acid
plants
Page
20
of
105
Table
3.2:
Summary
of
Metabolites
and
Degradates
to
be
Included
in
the
Risk
Assessment
and
Tolerance
Expression
for
Triadimefon.

Matrix
Residues
Included
in
Risk
Assessment
Residues
Included
in
Tolerance
Expression
Plants
Primary
crop
­
apple,
grape,
pear,
pineapple,
and
raspberry
triadimefon,
triadimenol,
KWG
1323,
and
KWG
1342
triadimefon
and
triadimenol
Rotational
crop
NA
=
not
applicable
NA
Livestock
Ruminant
NA
NA
Poultry
NA
NA
Drinking
water
triadimefon
and
triadimenol
NA
Page
21
of
105
4.0
HAZARD
CHARACTERIZATION
/
ASSESSMENT
4.1
Hazard
Profile
4.1.1
Studies
available
and
considered
(
animal,
human,
general
literature)

The
toxicological
database
contained
acceptable/
guideline
studies
including
acute
and
subchronic
neurotoxicity,
developmental,
chronic,
carcinogenicity,
combined
chronic
/
carcinogenicity,
and
subchronic
dermal
studies.
The
toxicological
database
also
contained
acceptable/
nonguideline
reproduction
studies.
The
database
is
also
supported
by
substantial
data,
including
some
studies
performed
by
EPA
scientists,
from
the
literature
that
supports
the
mode
of
toxic
action
and
endpoint
selection.
For
the
purposes
of
reregistration,
the
database
is
adequate
although
there
are
data
gaps
(
lack
of
developmental
neurotoxicity
and
an
inhalation
study).

4.1.2
Evidence
of
Neurotoxicity
(
Mode
of
Action,
Metabolism,
Toxicokinetic
Data)

The
active
ingredient,
triadimefon,
is
a
neurotoxic,
triazole
fungicide
pesticide.
Triadimenol,
a
major
mammalian
and
plant
metabolite
of
triadimefon,
is
also
another
neurotoxic
triazole
fungicide.
The
mode
of
toxic
action
for
both
triadimefon
and
triadimenol
involves
blocking
the
re­
uptake
of
dopamine
which
leads
to
increased
motor
activity
and
hyperactivity
in
rodents.
These
pesticides
act
as
indirect
dopamine
agonists
by
binding
to
the
dopamine
transporter
and
increasing
levels
of
synaptic
dopamine.

Triazole
fungicide
pesticides,
in
general,
are
believed
to
exhibit
their
fungicidal
activity
through
an
inhibition
of
ergosterol
biosynthesis,
leading
to
an
inhibition
of
cell
wall
percursors.
Crofton
(
1996)
evaluated
the
potential
for
14
triazole
fungicides
and
structurally
related
compounds.
The
purpose
was
to
screen
these
compounds
to
determine
whether
central
nervous
system
toxicity,
particularly
increased
motor
activity,
is
characteristic
of
other
triazole
fungicides.
Crofton
(
1996)
showed
that
of
the
chemicals
tested,
only
triadimefon
and
triadimenol
were
able
to
induce
hyperactivity;
none
of
the
other
triazoles
or
related
compounds
tested
produced
this
effect.
The
author
hypothesized
that
the
ether
oxygen
component
of
the
triadimenol
and
triadimefon
molecules
appears
to
be
an
important
structural
requirement
for
induction
of
hyperactivity
in
rats.
As
such,
at
this
time,
although
the
fungicidal
activity
of
triadimefon
and
triademenol
may
be
through
the
inhibition
of
sterol
sythesis,
the
primary
mode
of
toxicity
in
mammals
appears
to
be
neurotoxicity
mediated
through
an
indirect
monoaminergic
mechanism
that
appears
to
be
specific
to
triamidefon
and
triadimenol
only.

It
is
also
noted
that
triadimefon
and
triadimenol
share
toxicological
properties
with
methylphenidate.
Methylphenidate
is
a
central
nervous
system
stimulant
approved
by
the
Food
and
Drug
Administration
for
the
treatment
of
attention
deficit
hyperactivity
disorder
(
ADHD)
and
narcolepsy
in
persons
six
years
and
older.
d,
l­
Methylphenidate
is
marketed
under
the
names
Ritalin
®
,
Metadate
®
,
and
Concerta
®
.
Methylphenidate
is
believed
to
block
reuptake
of
norepinephrine
and
dopamine
by
the
presynaptic
neuron,
thus
increasing
levels
of
monoamine
Page
22
of
105
neurotransmitters
in
the
extra
neuronal
space.
As
methylphenidate
is
a
commonly
prescribed
human
drug,
there
is
extensive
metabolism
and
toxicity
data
in
humans
and
animals.
An
expert
panel
of
scientists
recently
reviewed
the
available
toxicity
and
metabolism
studies
regarding
methylphenidate
(
Golub
et
al,
2005).
Because
of
the
similar
toxicological
profiles
between
methylphenidate,
triadimefon
and
triadimenol,
at
present
time,
the
Agency
is
evaluating
the
extent
to
which
the
data
in
methylphenidate
may
be
used
to
inform
interspecies
extrapolation.
The
Agency
historically
uses
a
10X
factor
for
extrapolating
between
animals
and
humans.
This
10X
is
expected
to
account
for
differences
in
both
pharmacokinetic
and
pharmacodynamic
characteristics.
In
some
cases
where
the
mode
of
toxic
action
is
understood,
the
pharmacodynamics
are
believed
to
be
similar
for
animals
and
humans,
and
the
pharmacokinetic
differences
are
not
expected
to
exceed
3X,
so
the
interspecies
extrapolation
factor
may
be
reduced
to
3X.
The
current
risk
assessment
has
applied
the
default
10X
interspecies
extrapolation
factor.
The
Agency
is
currently
reviewing
the
available
pharmacokinetic
and
pharmacodynamic
properties
of
methylphenidate,
triadimefon
and
triadimenol
and
may
in
the
future
reconsider
the
magnitude
of
the
interspecies
factor.
However,
in
the
interim,
the
default
10X
interspecies
extrapolation
factor
will
be
utilized.

4.1.3
Toxicological
Effects
As
mentioned
above,
triadimefon
is
known
to
cause
neurotoxic
effects.
Acute
neurotoxic
signs
observed
in
mice,
rats,
and
rabbits
consisted
of
"
apathy,
labored
breathing,
increased/
decrease
mobility,
staggering
and
cramped
posture,
aggressiveness,
and
self­
mutilation"
(
MRID
00149331).
The
formulation
Bayleton
50%
Wettable
Powder,
has
been
shown
to
cause
hyperactivity,
biting
and
antagonism
behavior
in
rats,
and
the
durations
of
these
effects
were
doserelated
(
Mobay
Report
No.
88,
submitted
in
FIFRA
88,
Phase
III).
Baytan
(
triadimenol),
the
major
metabolite
of
triadimefon,
is
also
known
to
cause
CNS­
related
excitatory
effects
in
rats
and
mice
[(
from
the
memo
dated
February
27,
1992:
Triadimefon.
Section
18,
Ressuance
of
Emergency
Exemption
for
the
use
of
Bayleton
50%
Dry
Flowable
Fungicide
(
EPA
Reg.
No.
3125­
320)
to
control
Powdery
Mildew
on
artichokes
in
the
State
of
California)]).

The
neurotoxic
endpoint
seen
with
triadimefon
is
supported
by
the
results
of
numerous
studies
reported
in
the
open
literature.
In
fact,
the
motor
behavior
stimulant
effect
of
triadimefon
has
been
sufficiently
characterized
such
that
the
compound
was
used
as
a
prototype
in
an
interlaboratory
comparison
of
behavioral
toxicology
methods
(
Crofton
et
al.,
1991;
Moser
and
MacPhail,
1992).
In
addition,
triadimefon
is
used
in
contract
laboratories
as
a
positive
control
for
motor
activity
in
adults
animals
(
Crofton
et
al,
2004).
Doses
of
triadimefon
(
50­
100
mg/
kg)
have
been
reported
to
increase
locomotion
and
rearing
in
rats
(
Walker
et
al.,
1990).
The
highest
dose
of
triadimefon
tested
in
this
study
(
200
mg/
kg)
induced
three
stereotypic
behaviors:
head
weaving,
circling,
and
backward
locomotion
(
Walker
et
al.,
1990).
Crofton
et
al
(
1991)
reported
hyperactivity
in
rats
following
oral
exposure
to
triadimefon
with
LOAELs
ranging
from
50
to
100
mg/
kg.
Walker
and
Mailman
(
1996)
reported
that
acute
administration
of
triadimefon
and
triadimenol
resulted
in
a
neurotoxic
syndrome
in
rats
characterized
by
increased
motor
activity,
stereotyped
behaviors,
and
altered
monamine
metabolism.
Page
23
of
105
Similar
to
rodents,
humans
are
believed
to
exhibit
neurotoxicity
following
acute
exposures
to
triadimefon.
Several
letters
submitted
by
the
registrant
in
FIFRA
88
Phase
III
describe
neurological
adverse
symptoms
observed
in
humans,
from
1983
to
1989,
following
acute/
subacute
exposures
to
triadimefon.
One
female
who
was
exposed
to
triademifon
on
grass
sprayed
twice
with
the
pesticide,
reported
"
hyperactivity,
fatigue,
mood
shifts,
crying,
anxiety,
and
headache",
one
week
after
the
second
exposure.
Two
workers
spraying
triadimefon
on
lawns
reported
"
nausea
and
generalized
weakness"
during
and
after
the
acute
exposure.
A
woman
exposed
to
a
spill
of
Bayleton
50%
Wettable
Powder
reported
acute
headache
followed
by
delayed
(
one­
month)
numbness
of
hands.
A
farmer
applying
triadimefon
to
grapes
experienced
perioral
and
tongue
numbness
followed
overnight
by
extreme
weakness,
and
after
a
few
days,
by
polyreticular
and
bulbar
neuropathy
(
lower
extremities
were
affected
more
than
upper
extremities
+
loss
of
deep
tendon
reflexes
(
from
the
memo
dated
February
27,
1992:
Triadimefon.
Section
18,
Ressuance
of
Emergency
Exemption
for
the
use
of
Bayleton
50%
Dry
Flowable
Fungicide
(
EPA
Reg.
No.
3125­
320)
to
control
Powdery
Mildew
on
artichokes
in
the
State
of
California).

As
described
below,
NOAELs
and
LOAELs
for
both
acute
and
subchronic
(
90
days)
exposures
in
guideline
studies
are
similar
suggesting
that
the
neurotoxicity
resulting
from
exposure
to
triadimefon
do
not
accumulate.
Similarly,
no
accumulation
of
toxicity
was
observed
in
studies
by
Crofton
et
al
(
1988)
and
Moser
et
al
(
1995)
following
seven
and
fourteen
days
of
exposure,
respectively.
Further
evidence
is
also
provided
by
Ikaiddi
et
al
(
1997)
who
showed
lack
of
accumulation
of
neurotoxicity
following
14
days
of
dosing
with
some
tolerance
on
aminergic
endpoints.
The
Agency
notes
that
the
dose
spacing
between
the
NOAEL
and
LOAELs
in
the
guideline
acute
and
subchronic
neurotoxicity
studies
are
fairly
large
(>
10­
fold).
This
large
dose
spacing
may
contribute
to
the
conservative
nature
of
the
current
risk
assessment.
As
the
Agency
refines
its
preliminary
risk
assessment
for
triadimefon
in
the
coming
months,
dose­
response
studies
from
the
literature
may
provide
additional
information
for
the
hazard
characterization
of
triadimefon.

In
the
available
chronic
studies,
FOBs
and
motor
activity
were
not
measured
and
as
such,
hyperactivity
was
generally
not
observed.
Liver
toxicity
was
noted
in
chronic
studies
with
rats,
mice,
and
dogs.
Specifically,
changes
in
liver
enzymes
were
noted
in
the
dog
and
mouse
study.
Changes
in
liver
weights
were
noted
in
rats
and
mice.
Increased
incidence
of
hepatocellular
hypertrophy
in
both
sexes
were
noted
in
mice.

4.1.4
Dose­
Response
Acute
Neurotoxicity:
In
an
acute
oral
neurotoxicity
study
(
MRID
43936101),
twelve
Wistar
(
Hsd
Win:
WU)
rats/
sex/
group
were
dosed
by
gavage
with
nominal
dose
of
0,
2,
35,
450
(
females
only),
or
600
(
males
only)
mg/
kg
of
triadimefon
(
MEB
6447;
95.8%
a.
i.;
Lot
No.:
203480004)
in
polyethylene
glycol
400
(
5
mL/
kg).
Analytically
confirmed
doses
were
0,
2,
31.2,
424.4
mg/
kg
(
females
only)
and
587.4
mg/
kg
(
males
only).
The
animals
were
monitored
for
a
14­
day
observation
period.
All
twelve
rats/
sex/
group
were
tested
in
the
functional
observational
battery
(
FOB)
and
motor
activity
(
MA)
measurements,
and
six
rats/
sex/
group
were
perfused
for
Page
24
of
105
neuropathology.

Within
two
days
after
dosing,
one
high­
dose
male
and
four
high­
dose
females
died.
Clinical
signs
were
observed
in
the
mid­
and
high­
dose
males
and
high­
dose
females.
Mid­
dose
males
exhibited
moderate
hyperactivity.
High
dose
rats
showed
signs
of
severe
hyperactivity,
stereotypic
behavior,
self­
mutilation,
diarrhea,
and
increased
rearing.
Decreased
body
weights
were
observed
on
Day
7
in
high­
dose
males
(­
7.6%;
p<
0.05)
and
females
(­
4.5%;
n.
s.).

Dose­
related
effects
were
observed
in
the
Functional
Operational
Battery
in
mid­
and
high­
dose
males
and
females.
On
day
0,
hyperactivity
was
indicated
by
affected
posture
and
gait,
increased
mobility,
searching
and
cleaning
gestures,
stereotypy,
increased
arousal,
and
increased
open
field
rearing
incidence.
Hyperactivity,
indicated
by
an
increased
incidence
of
open
field
rearing,
was
still
observed
at
day
7
or
day
14
in
mid­
or
high­
dose
males,
respectively.
In
mid­
dose
females,
rearing
were
increased
at
day
7
with
complete
reversibility
at
day
14.
Body
temperatures
were
significantly
(
p<
0.05)
increased
in
high­
dose
males
and
females
compared
to
controls.

Grip
strength
was
marginally
decreased
in
high­
dose
males
and
females
on
days
7
and
14
(
males
only).
Hindlimb
foot
splay
was
decreased
in
high­
dose
males
on
days
0
and
7.
Functional
Operational
Battery
effects
were
completely
reversible
until
the
end
of
the
study
in
females
and
largely
reversible
in
males.

On
day
0,
mid­
and
high­
dose
males
and
females
exhibited
statistically
significant
increases
(
226.9­
317.5%)
in
motor
activity.
On
day
7,
mid­
dose
males
still
had
a
statistically
significant
increase
(
33.6%)
in
motor
activity
(
interval
50­
60
minutes),
while
a
nonstatistically
significant
increase
(
26.2%)
was
present
on
day
14
(
intervals
30­
60
minutes).
Mid­
dose
females
exhibited
marginal
increases
in
motor
activity
on
days
7(
46.7%)
and
14
(
34.2%).

Statistically
significant
increases
(
326.7­
485.6%)
in
locomotor
activity
were
observed
in
mid­
and
high­
dose
males
and
females
on
day
0
persisting
until
the
end
of
the
study
period
(
Day
14)
though
to
a
lesser
extent
(
28.1
­
50.25%).
Statistically
significantly
decreased
habituation
was
noted
in
mid­
and
high­
dose
the
males
and
females
on
day
0.
This
continued
to
a
smaller
degree
for
middose
males
and
females
on
day
7
and
for
mid­
and
high­
dose
males
on
day
14.
The
blind
alley
and
figure­
eight
activities
were
increased
for
mid­
and
high­
dose
males
and
females
on
day
0.

No
effect
on
the
absolute
or
relative
brain
weights
was
observed.
No
treatment­
related
gross
effects
or
histopathology
were
observed.

The
LOAEL
for
systemic/
neurobehavioral
findings
is
31.2
mg/
kg
based
on
clinical
signs,
FOB,
rearing,
body
temperature,
MA,
habituation,
and
spatial
distribution
in
males
and
females.
The
NOAEL
is
2
mg/
kg.

Subchronic
Neurotoxicity:
In
a
subchronic
neurotoxicity
screening
(
MRID
44153501),
triadimefon
(
MEB
6477)
technical
(
95.8­
95.9%
a.
i.)
was
administered
in
the
diet
to
18
Wistar
Page
25
of
105
rats/
sex/
dose
at
levels
of
0,
50,
800,
or
2,200
ppm
(
0,
3.4,
54.6
and
149.8
mg/
kg/
day
for
males
and
0,
4.3,
68.7,
and
189.7
mg/
kg/
day
for
females)
for
13­
weeks.
Six
rats/
sex/
dose
level
were
subjected
to
neuropathological
evaluations
at
the
end
of
the
exposure
period
and
the
remaining
12
rats/
sex/
dose
level
were
observed
for
another
4
(
males)
or
10
(
females)
weeks
to
investigate
the
persistence
of
the
toxicological
effects.

At
800
ppm
(
54.6/
68.7
M/
F)
there
were
increases
in
rearing
(
both
sexes),
motor
and
locomotor
activity
(
females
only)
and
other
indications
of
hyperactivity,
especially
in
females,
including
clinical
signs
(
mobility,
digging
and
spilling
food
and
water);
body
weight
and
gain
were
also
decreased
(
9%
%
and
14%
&)
in
both
sexes
in
the
initial
four
weeks
of
dosing.
There
were
also
slight
(
not
statistical
significant)
increases
in
male
brain
relative
weight
and
grip
strength.
At
2200
ppm
(
149.8/
189.7M/
F)
there
was
stereotypy
(
pacing
only
in
a
few
rats)
and
increased
relative
brain
weight
(
18%
both
sexes).
Increased
landing
foot
splay
and
grip
strength
were
also
evident.
The
effects
were
considered
slowly
reversible,
however,
there
was
some
evidence
of
hyperactivity
persisting.
The
LOAEL
for
neurotoxicity
is
800
ppm
(
54.6%
and
68.7&
mg/
kg/
day)
based
largely
on
hyperactivity.
The
NOAEL
is
50
ppm
(
3.4%
and
4.3&
mg/
kg/
day).

Developmental
Toxicity
Study:
Similar
signs/
effects
of
neurotoxicity
from
the
acute
and
subchronic
neurotoxicity
studies
were
seen
in
the
developmental
toxicity
study
(
MRID
00089023)
where
the
maternal
NOAEL
is
10
mg/
kg/
day
and
the
LOAEL
is
50
mg/
kg/
day
based
on
a
doserelated
increase
in
both
degree
and
duration
of
motor
activity
and/
or
depression
of
maternal
weight.

Additional
Information
from
Literature
Sources
The
following
references
were
obtained
from
the
open
literature;

1)
Crofton,
KM..,
Boncek,
VM.,
and
Reiter,
LW..
1988.
Hyperactivity
induced
by
triadimefon,
a
triazole
fungicide.
Fundam.
Appl.
Toxicol.
10,
459­
465.

2)
Crofton,
KM..,
Boncek,
VM.,
and
MacPhail,
RC.
1989.
Evidence
for
monoaminergic
involvement
in
triadimefon
­
induced
hyperactivity,
Psychopharmacology
97,
326­
330.

3)
Moser,
VC
and
MacPhail,
RC.
1989.
Neurobehavioral
effects
of
triadimefon,
a
triazole
fungicide,
in
male
and
female
rats.
Neurotoxicol.
Teratol.
11,
285­
293.

4)
Crofton,
KM..,
Howard,
JL.,
Moser,
VC.,
Gill,
MW,
et
al.
1991.
Interlaboratory
comparison
of
motor
activity
experiments:
implications
for
neurotoxicological
assessments.
Neurotoxicol.
Teratol.
13
(
6):
599­
609.

5)
Moser,
VC
and
MacPhail,
RC.
1992.
International
validation
of
the
neurobehavioral
screening
battery:
The
IPCS/
WHO
collaborative
study.
Toxicol.
Lett.
64­
65
Spec.
No.,
Page
26
of
105
217­
223.

6)
Crofton,
KM.
1996.
A
structure­
activity
relationship
for
the
neurotoxicity
of
triazole
fungicites.
Toxicol.
Lett
84
(
3):
155­
159.

7)
Walker,
QD
and
Mailman,
RB.
1996.
Triadimefon
and
triadimenol:
effects
on
monoamine
uptake
and
release.
Toxicol.
Appl.
Pharmacol.
139
(
2):
227­
233.

8)
Ikaiddi,
MU.,
Akunne,
HC.,
and
Soliman.,
KE.
1997.
Behavioral
and
neurochemical
effects
of
acute
and
repeated
administration
of
triadimefon
in
the
male
rat.
Neurotoxicology
18(
3):
771­
80.

9)
Crofton,
KM
.,
Makris,
SL.,
Sette,
WF.,
Mendez,
E.,
and
Raffaele,
KC.
2004.
A
qualitative
retrospective
analysis
of
positive
control
data
in
developmental
neurotoxicity
studies.
Neurotocicology
and
Teratology
26;
345­
352.

10)
Golub,
M.,
Costa,
L.,
Crofton,
K.,
Frank,
D.,
Fried,
P.,
Gladen,
B.,
Henderson,
R.,
Liebelt,
E.,
Lusskin,
s.,
Marty,
S.,
Rowland,
A.,
Scialli,
J.,
and
Vore,
M.
2005.
NTPCERHR
expert
panel
report
on
the
reproductive
and
developmenal
toxicity
of
methylphenidate.
Birth
Defects
Research
(
part
B)
74:
300­
381.
Page
27
of
105
Table
4.1
Acute
Toxicity
Profile
Guideline
No.
Study
Type
MRID(
s)
Results
Toxicity
Category
870.1100
Acute
oral
­
rat
264276
LD50
=
1470
mg/
kg
(
Males)
LD50
=
1090
mg/
kg
(
Females)
III
870.1200
Acute
dermal­
rabbit
264276
LD50
>
2000
mg/
kg
III
870.1300
Acute
inhalation
­
rat
41616002
LC50
>
3.570
mg/
L
IV
870.2400
Acute
eye
irritation
­
rabbit
41782501
Slightly
irritating
IV
870.2500
Acute
dermal
irritation
­
rabbit
41616004
Not
an
irritant
IV
870.2600
Skin
sensitization
­
guinea
pig
41554001
Sensitizer
Not
Applicable
Table
4.2
Triadimefon
Technical
:
Toxicology
Profile
Guideline
No./
Study
Type
MRID
No.
(
year)/
Classification
/
Doses
Results
870.3100a
90­
Day
oral
toxicity
(
rats)
00048624
Acceptable/
guideline
0,
50,
200,
800
and
2000
ppm
(
0,
2.5,
10,
40
and
100
mg/
kg/
day)
NOAEL
>
2000
ppm
(
100
mg/
kg/
day)
(
HDT).
Decreased
body
weight
gain
and
food
consumption
at
2000
ppm
(
100
mg/
kg/
day)
was
attributed
to
palatability.

The
LOAEL
was
not
observed.

870.3100
30­
Day
oral
toxicity
(
rats)
00048627
Acceptable/
guideline
0,
3,
10,
or
30
mg/
kg/
day
NOAEL
is
10
mg/
kg/
day.
The
LOAEL
is
30
mg/
kg/
day
based
on
increased
liver
weights.

870.3100b
90­
Day
oral
toxicity
(
dogs)
00048625
&
00060226
(
1974)
Acceptable/
guideline
0,
150,
600
and
2400
ppm
(
0,
3.75,
15,
and
60mg/
kg/
day)
NOAEL
>
2400
ppm
(
60mg/
kg/
day)
(
HDT).
Decreased
body
weight
gain
and
food
consumption
at
2400
ppm
(
60mg/
kg/
day)
was
attributed
to
palatability.

The
LOAEL
was
not
observed.
Table
4.2
Triadimefon
Technical
:
Toxicology
Profile
Guideline
No./
Study
Type
MRID
No.
(
year)/
Classification
/
Doses
Results
Page
28
of
105
870.3200
21­
Day
dermal
toxicity
(
rats)
42341501
(
1992)
Acceptable/
guideline
0,
100,
300,
or
1000
mg/
kg
bw/
day
NOAEL
is
300
mg/
kg/
day.
The
LOAEL
was
1000
mg/
kg/
day
based
on
increased
reactivity
and
activity
in
the
females.

870.3700a
Prenatal
developmental
in
(
rats)
00089023
(
1981)
Acceptable/
guideline
0,
10,
25,
50,
or
100
mg/
kg
bw/
day
Maternal
NOAEL
is
10
mg/
kg/
day
and
the
LOAEL
is
25
mg/
kg/
day
based
on
dose­
related
increase
in
both
degree
and
duration
of
motor
activity
and/
or
depression
of
maternal
weight.

Developmental
NOAEL
is
50
mg/
kg/
day
and
the
LOAEL
is
100
mg/
kg/
day
based
on
increased
incidences
of
cleft
palates;
two
fetuses
from
two
different
litters
were
found
to
have
cleft
palate.

870.3700a
Prenatal
developmental
in
(
rats)
00149336
&
92188018
(
1990)
Acceptable/
guideline
0,
10,
30,
or
90
mg/
kg
bw/
day
Maternal
NOAEL
is
30
mg/
kg/
day
and
the
LOAEL
is
90
mg/
kg/
day
based
on
decreased
body
weight
gains.

Developmental
NOAEL
is
30
mg/
kg/
day.
The
LOAEL
is
90
mg/
kg/
day
based
on
increased
incidences
of
distended
urinary
bladders
and
abnormal
ribs
(
extra
ribs
and
rib
buds).

870.3700b
Prenatal
developmental
in
(
rabbits)
41446201
&
42089601
(
1990)
Acceptable/
guideline
0,
20,
50,
or
120mg/
kg
bw/
day
Maternal
NOAEL
is
50
mg/
kg/
day
and
the
LOAEL
is
120
mg/
kg/
day
based
on
minor
decreases
in
initial
body
weight
gains,
placental
weights,
and
fetal
weights
and
on
initial
decreased
food
consumption.

Developmental
NOAEL
is
20
mg/
kg/
day.
The
LOAEL
is
50
mg/
kg/
day
based
on
dose­
related
increases
in
the
incidences
of
incomplete
ossification
of
the
pelvis
pubes
and
anterior
and
posterior
phalanges
and
irregular
spinous
processes
on
the
scapula.
Table
4.2
Triadimefon
Technical
:
Toxicology
Profile
Guideline
No./
Study
Type
MRID
No.
(
year)/
Classification
/
Doses
Results
Page
29
of
105
870.3800
Reproduction
and
fertility
effects
(
rats)
00155075,
92188019
&
92188320
(
1984)
Acceptable/
nonguideline
0,
50,
or
1800
ppm
(
0,
2.5,
90
mg/
kg/
day)

The
reproductive
study
in
the
rat
is
acceptable/
nonguideline
in
conjunction
with
the
3­
generation
study
(
MRID
00032541).
Parental/
Systemic/
Reproductive
toxicity
NOAEL
was
not
established
because
of
the
equivocal
findings
on
body
weights
in
the
F1
dams
and
ovary
weights
in
the
P
dams
at
2.5
mg/
kg/
day.

Offspring
NOAEL
is
2.5
mg/
kg/
day
and
the
LOAEL
is
90
mg/
kg/
day
based
on
decreased
pup
weights
and
viability
in
the
F1
and
F2
generations
and
decreased
litter
size
in
the
F2
generation.

Based
on
the
combined
two
studies
the
Parental
systemic/
Reproductive
toxicity
NOAEL
is
15
mg/
kg/
day
and
the
LOAEL
is
90
mg/
kg/
day.
The
Offspring
NOAEL
is
2.5
mg/
kg/
day
and
the
LOAEL
is
90
mg/
kg/
day.

870.3800
Reproduction
and
fertility
effects
(
3
­
Gen)
(
rats)
00032541
(
1979)
Acceptable/
nonguideline
0,
50,
300,
or
1800
ppm
(
0,
2.5,
15,
and
90
mg/
kg/
day)

The
reproductive
study
in
the
rat
is
acceptable/
nonguideline
in
conjunction
with
the
multi
generation
reproduction
study
(
MRID
00155075)
Parental
systemic/
Reproductive
toxicity
NOAEL
is
15
mg/
kg/
day
and
the
LOAEL
is
90
mg/
kg/
day
based
on
decreased
fertility,
body
weights,
body
weight
gains,
and
litter
size.

Offspring
NOAEL
and
LOAEL
is
equivocal
due
to
severe
reproductive
effects
(
In
the
F1
pups,
at
90
mg/
kg/
day,
the
number
of
offspring
per
dam
was
decreased
(
p<
0.05)
in
the
F1a
and
F1b
litters
(
decr.
20­
31%)
at
post­
natal
day
(
PND)
5.
At
PND
28,
viability
was
decreased
(
p<
0.01)
in
the
F1a
(
90.7%
treated
vs
97.8%
controls)
and
F1b
(
56.4%
treated
vs
84.2%
controls)
pups.
Additionally,
body
weight
gains
of
the
F1a
pups
were
decreased
(
decr.
10%;
p<
0.05)
during
lactation).

Based
on
the
combined
two
studies
the
Parental
systemic/
Reproductive
toxicity
NOAEL
is
15
mg/
kg/
day
and
the
LOAEL
is
90
mg/
kg/
day.
The
Offspring
NOAEL
is
2.5
mg/
kg/
day
and
the
LOAEL
is
90
mg/
kg/
day.
Table
4.2
Triadimefon
Technical
:
Toxicology
Profile
Guideline
No./
Study
Type
MRID
No.
(
year)/
Classification
/
Doses
Results
Page
30
of
105
870.4100b
Chronic
toxicity
(
dogs)
00032539
&
00126261
(
1978)
Acceptable/
guideline
0,
100,
or
330,
or
1000
ppm
(
wk
1 
54),
or
2000
ppm
(
wk
55­
104)

M:
0,
3.03,
11.42,
34.70
(
wk
1­
54)
or
68.80
(
wk
55­
104)
mg/
kg
bw/
day
F:
0,
3.49,
11.96,
33.67
(
wk
1­
54)
or
60.42
(
wk
55­
104)
mg/
kg
bw/
day
NOAEL
is
330
ppm
(
equivalent
to
11.42/
11.96
mg/
kg/
day
in
males/
females).

LOAEL
is
1000
ppm
(
equivalent
to
34.70/
33.67
mg/
kg/
day
in
males/
females),
based
on
increased
alkaline
phosphatase
levels
in
both
sexes;
and
decreased
food
consumption
and
increased
cholesterol
in
females.
Table
4.2
Triadimefon
Technical
:
Toxicology
Profile
Guideline
No./
Study
Type
MRID
No.
(
year)/
Classification
/
Doses
Results
Page
31
of
105
870.4200b
Carcinogenicity
(
mice)
40752101&
40865101
(
1986)
Acceptable/
guideline
0,
50,
300,
or
1800
ppm
M:
13.5,
76.0,
or
550.1
mg/
kg/
day
F:
0,
19.6,
119.4
or
765
mg/
kg/
day
NOAEL
is
50
ppm
(
equivalent
to
13.5/
19.6
mg/
kg/
day
in
males/
females).

LOAEL
is
300
ppm
(
equivalent
to
76.0/
119.4
mg/
kg/
day
in
males/
females)
based
on
hepatocellular
hypertrophy
in
both
sexes;
increased
liver
weights
in
males;
and
Kupffer
cell
proliferation,
single
cell
necrosis
and
pigment
accumulation
in
the
liver
of
females.

At
the
doses
tested,
the
carcinogenic
potential
of
MEB
6447
in
mice
is
positive.
There
was
a
treatment­
related
increase
(
p<=
0.05,
study
authors)
in
hepatocellular
adenomas.
The
incidence
at
the
high
dose
(
22%
in
males
and
18%
in
females)
exceeded
the
concurrent
controls
(
4­
6%)
and
the
historical
controls
(
0­
18.4%
[
mean=
5.9%]
in
males
and
0­
2%
[
mean=
0.3%]
in
females).
A
positive
trend
(
p<
0.01,
Agency
reviewers,
TXR
#
007294)
in
combined
liver
nodules
and
hepatocellular
adenoma
was
observed.
Furthermore,
an
increased
incidence
(
p<
0.01,
Agency
reviewers,
TXR
#
007294)
of
combined
liver
nodules
and
hepatocellular
adenomas
was
observed
at
the
high
dose
in
both
sexes.
Dosing
was
considered
adequate
based
on
hepatotoxicity
in
both
sexes
at
>=
300
ppm;
and
decreased
body
weights
and
body
weight
gain
and
increased
overall
food
and
water
consumption
in
males
at
1800
ppm.

870.4300
Combined
Chronic/
Carcinogenicity
(
rats)
42153901
(
1991)
Acceptable/
guideline
0,
50,
300,
or
1800
ppm
M:
0,
2.7,
16.4,
or
114.0
mg/
kg/
day
F:
0,
3.6,
22.5,
or
199.0
mg/
kg/
day
NOAEL
is
300
ppm
(
equivalent
to
16.4/
22.5
mg/
kg/
day
in
males/
females).

LOAEL
is
1800
ppm
(
equivalent
to
114.0/
199.0
mg/
kg/
day
in
males/
females)
based
on
increased
food
consumption
in
both
sexes,
incidence
of
fat
in
the
hepatocytes
in
both
sexes,
alanine
aminotransferase
levels
in
males,
cholesterol
levels
in
females,
and
absolute
and
relative
(
to
body)
liver
weights
in
females,
and
decreased
body
weight
and
body
weight
gains
in
females.

At
the
doses
tested,
the
carcinogenic
potential
of
MEB
6447
is
equivocal
based
on
the
incidence
of
thyroid
adenomas
and
cystic
hyperplasia
in
both
sexes.
Table
4.2
Triadimefon
Technical
:
Toxicology
Profile
Guideline
No./
Study
Type
MRID
No.
(
year)/
Classification
/
Doses
Results
Page
32
of
105
870.5100
Bacterial
system
099412
7
099413
acceptable/
guideline
negative
870.5395
Micronucleus
assay
00048637
(
1977)
acceptable/
guideline
negative
870.5450
Cytogenetics
dominant
lethal
assay
00048628
(
1976)
acceptable/
guideline
negative
870.5550
DNA
damage/
Repair
00159343
(
1985)
negative
870.6200a
acute
neurotoxicity
screening
battery
(
rats
43495509
(
1992)
unacceptable/
non­
guideline
0,
30,
100,
300
mg/
kg/
day
No
definative
NOAEL
or
LOAEL
could
be
established
870.6200a
acute
neurotoxicity
screening
battery
(
rats)
43936101
(
1996)
Acceptable/
guideline
0,
2,
31.2,
424.4
(
females
only)
and
587.4
(
males
only)
The
NOAEL
is
2
mg/
kg.

The
LOAEL
for
systemic/
neurobehavioral
findings
is
31.2
mg/
kg
based
on
clinical
signs,
FOB,
rearing,
body
temperature,
MA,
habituation,
and
spatial
distribution
in
males
and
females.

870.6200b
Subchronic
neurotoxicity
screening
battery
(
rats)
44153501
(
1996)
Acceptable/
guideline
0,50,800,
or
2200
ppm
M:
0,
3.4,
54.6
or
149.8
mg/
kg/
day
F:
0,4.3,
68.7,
or
189.7
mg/
kg/
day
NOAEL
is
50
ppm
(
3.4
and
4.3
mg/
kg/
day,
males/
females,
respectively).

LOAEL
for
neurotoxicity
is
800
ppm
(
54.6
and
68.7
mg/
kg/
day
males/
females
respectively)
based
largely
on
hyperactivity.
Table
4.2
Triadimefon
Technical
:
Toxicology
Profile
Guideline
No./
Study
Type
MRID
No.
(
year)/
Classification
/
Doses
Results
Page
33
of
105
870.7485
Metabolism
and
pharmacokinetics
(
rats)
42409101(
1992)
Acceptable/
guideline
5
or
50
mg/
kg
Radioactivity
was
not
detected
in
the
expired
air.
The
overall
recovery
of
radioactivity
was
97­
112%.
The
compound
was
predominantly
excreted
(
90­
98%
dose)
within
4
days.
The
excretion
profile
of
the
repeated
lowdose
group
was
similar
to
the
single
low­
dose
group;
however,
the
excretion
profiles
were
sex­
dependent.
Over
a
4
day­
period,
recovery
in
the
urine
was
24­
28%
dose
in
males
and
57­
66%
in
females,
and
recovery
in
feces
was
63­
66%
in
males
and
32­
40%
in
females.
Thus,
based
on
urinary
excretion,
absorption
was
at
least
24%
dose
in
males
and
57%
in
females.

Less
than
1%
dose
remained
in
the
body
4
days
after
treatment.
Bioaccumulation
was
not
indicated.
Tissue
residues
were
highest
in
the
liver
(
0.088­
1.94
ppm)
and
kidney
(
0.041­
0.38
ppm),
and
were
generally
slightly
higher
in
males
than
in
females.
RP­
HPLC
analyses
revealed
the
presence
of
15
radioactive
components
in
the
urine
and
12
in
the
feces.
The
4
major
metabolites
(
1­
14%
dose,
each)
in
the
urine
of
both
sexes
were:
KWG
0519
acid
(
2
isomers),
KWG
1323­
gluc,
HO­
DeMEKWG
1342
(
2
isomers),
and
DeMe­
KWG
132­
gluc
(
2
isomers).
The
5
major
metabolites
(
1­
15%
dose,
each)
in
the
feces
of
both
sexes
were:
KWG
0519
acid
(
2
isomers),
KWG
1323­
gluc,
KWG
1323,
KWG
1342,
and
KWG
0519
dehydrate.
Thus,
metabolism
of
this
compound
proceeded
along
several
pathways,
such
as:
(
i)
hydroxylation
at
the
t­
butyl
moiety
and
oxidation
to
the
acid
or
glucuronidation;
(
ii)
reduction
of
the
keto
group
and
subsequent
reactions
(
including
sulfate
conjugation);
and
(
iii)
desmethylation
followed
by
glucuronidation.
Table
4.2
Triadimefon
Technical
:
Toxicology
Profile
Guideline
No./
Study
Type
MRID
No.
(
year)/
Classification
/
Doses
Results
Page
34
of
105
870.7485
Metabolism
and
pharmacokinetics
(
rats)
00033057(
1979)
Acceptable/
guideline
24.5­
25.0
mg/
kg
Radioactivity
was
not
detected
in
the
expired
air
of
animals.
Over
a
7
day­
period,
recovery
in
the
urine
was
29.8%
dose
in
males
and
39.9%
in
females,
and
recovery
in
feces
was
52.7%
in
males
and
34.5%
in
females.
Thus,
based
on
urinary
excretion,
absorption
was
at
least
29.8%
dose
in
all
animals.

Plasma
levels
of
radioactivity
were
highest
1­
2
hours
post­
dose
(
2.5­
3.2
ppm),
and
the
half­
life
(
calculated
by
the
reviewer)
was
about
4
hours.
Tissue
concentrations
in
males
were
generally
similar
to
females.
The
highest
concentrations
of
radioactivity
were
found
in
the
fat
(
43.5­
45.0
ppm)
at
4­
8
hours
post­
dose.
Approximately
50%
of
the
radiolabeled
compound
in
the
fat
of
males
was
unchanged
Bayleton
and
50%
was
isomeric
forms
of
the
2­
butanol
derivative
KWG
0519;
over
90%
was
Bayleton
in
females.
In
addition,
relatively
high
concentrations
of
radioactivity
were
observed
in
the
liver
(
26.2­
28.4
ppm)
and
skin
(
21­
22
ppm)
at
2
hours
post­
dose.
Tissue
concentrations
were
<
0.14
ppm
at
7
days
post­
dose.

In
the
urine,
the
major
component
of
the
acidified
extract
was
KWG
0519
acid
(
6.1­
7.7%
dose).
In
the
direct
extract
of
urine,
3
minor
metabolites
were
identified:
pchlorophenol
KWG
1323,
and
KWG
1342
(
two
isomers).
In
the
direct
extract
of
the
feces,
KWG
1323,
KWG
1342,
and
KWG
0519
acid
(
5.7­
20.0%
dose)
were
identified.
KWG
1323
was
the
predominant
metabolite
in
the
feces
of
females
(
12.7%
dose),
and
KWG
0519
acid
was
the
predominant
metabolite
in
the
feces
of
males
(
20.0%
dose).
Thus,
the
major
metabolites
were
the
alcohol
and
acid
of
Bayleton,
which
were
formed
by
the
sequential
hydroxylation
and
oxidation
of
the
methyl
group
of
the
t­
butyl
chain.
Page
35
of
105
4.2
FQPA
Considerations
4.2.1
Adequacy
of
the
Toxicity
Data
Base
The
toxicological
database
contained
acceptable/
guideline
studies
including
acute
and
subchronic
neurotoxicity,
developmental,
chronic,
carcinogenicity,
combined
chronic
/
carcinogenicity,
and
subchronic
dermal
studies.
The
toxicological
database
also
contained
acceptable/
nonguideline
reproduction
studies.
The
database
is
also
supported
by
substantial
data,
including
some
studies
performed
by
EPA
scientists,
from
the
literature
that
supports
the
mode
of
action
and
endpoint
selection
(
see
section
4.1
thru
4.1.3
for
more
specific
detail).
For
the
purposes
of
reregistration,
the
database
is
adequate
although
there
are
data
gaps
(
lack
of
developmental
neurotoxicity
and
an
inhalation
studies).

4.2.2
Developmental
Toxicity
Studies
Rat
Developmental:
In
a
rat
developmental
study
(
MRID
00089023),
Sprague­
Dawley
rats
(
19­
21/
dose)
received
triadimefon
(
99%)
in
0.5%
Cremaphor
suspension
at
dose
levels
of
0,
10,
25,
50,
or
100
mg/
kg/
day
from
days
6
thru
15
of
gestation.
Maternal
toxicity
manifested
as
increased
motor
activity
in
dams
at
25,
50
or
100
mg/
kg/
day.
The
degree
and
duration
of
these
episodes
were
dose­
related.
In
addition,
dams
at
50
and
100
mg/
kg/
day
exhibited
a
statistically
significant
decrease
in
body
weight
gain
during
the
dosing
period.
Overall
weight
gain,
however,
was
not
affected
in
these
dams.
For
maternal
toxicity,
the
NOAEL
was
10
mg/
kg/
day
and
the
LOAEL
was
25
mg/
kg/
day,
based
on
dose­
related
increases
in
both
degree
and
duration
of
motor
activity
and/
or
depression
of
maternal
weight.
For
developmental
toxicity,
the
NOAEL
is
50
mg/
kg/
day
and
the
LOAEL
was
100
mg/
kg/
day,
based
on
increased
incidences
of
cleft
palates;
two
fetuses
from
two
different
litters
were
found
to
have
cleft
palates.

Prenatal
Developmental:
In
a
prenatal
developmental
toxicity
study
(
MRIDs
00149336
and
92188018),
Bayleton
(
triadimefon;
93.2%
a.
i.,
Lot/
Batch
#
not
provided)
in
0.5%
Cremophor
EL
Emulsion
was
administered
to
pregnant
CD­
SD
rats
(
26/
dose)
via
gavage
in
a
dosing
volume
of
10
mL/
kg
at
concentrations
of
0,
10,
30,
or
90
mg/
kg/
day
on
gestation
days
(
GDs)
6
through
15.
All
dams
were
sacrificed
on
GD
20
and
their
uterine
contents
examined.
There
were
no
unscheduled
deaths
during
the
study.
When
compared
to
concurrent
controls,
there
were
no
effects
of
treatment
on
maternal
clinical
observations,
gross
pathology,
histopathology,
number
of
implantations,
viable
fetuses,
early
resorptions,
non­
viable
implantations/
dam,
live
litters,
fetuses/
dam,
percent
males,
or
fetal
weight.
Maternal
body
weight
gains
were
decreased
during
dosing
(
decr.
24%;
p<
0.05).
There
was
an
increase
in
late
resorptions
at
90
mg/
kg
(
3%
treated
vs
0%
controls;
not
significant).
It
was
considered
not
to
be
adverse
because
it
was
minor
and
did
not
affect
the
number
of
live
litters
or
fetuses/
dam.
The
maternal
LOAEL
is
90
mg/
kg/
day
based
on
decreased
body
weight
gains.
The
maternal
NOAEL
is
30
mg/
kg/
day.

At
90
mg/
kg/
day,
incidences
of
distended
urinary
bladders
were
increased
(
p<
0.05)
over
controls
(
2.6%
of
the
fetuses
in
4
litters
vs
0
controls).
The
incidence
of
abnormal
ribs
was
significantly
Page
36
of
105
increased
at
this
dose
(
35.7%
of
the
fetuses
in
19
litters)
compared
to
controls
(
0.6%
of
the
fetuses
in
1
litter).
Specifically,
increased
incidences
of
extra
ribs
(
33.1%
of
the
fetuses
in
18
litters)
and
rib
buds
(
30.2%
of
the
fetuses
in
18
litters)
were
observed
compared
to
0.6%
of
the
fetuses
in
1
litter
each
control.
The
developmental
LOAEL
is
90
mg/
kg/
day
based
on
increased
incidences
of
distended
urinary
bladders
and
abnormal
ribs
(
extra
ribs
and
rib
buds).
The
developmental
NOAEL
is
30
mg/
kg/
day.

Prenatal
Developmental:
In
a
prenatal
developmental
toxicity
study
(
MRIDs
41446201
&
42089601),
Bayleton
(
triadimefon;
94.3%
a.
i.,
Lot/
Batch
#
203
780190)
in
aqueous
0.5%
(
w/
v)
carboxymethylcellulose
and
0.4%
(
w/
v)
Tween
80
was
administered
to
pregnant
American
Dutch
rabbits
(
20/
dose)
via
gavage
in
a
dosing
volume
of
5
mL/
kg
at
concentrations
of
0,
20,
50,
or
120
mg/
kg/
day
on
gestation
days
(
GDs)
6
through
18.
All
dams
were
sacrificed
on
GD
28
and
their
uterine
contents
examined.
There
were
no
unscheduled
deaths
during
the
study.
When
compared
to
concurrent
controls,
there
were
no
effects
of
treatment
on
maternal
body
weights,
clinical
signs,
gross
pathology,
gestation
indices,
numbers
of
resorptions,
fetuses/
litter,
viable
fetuses/
doe,
post­
implantation
loss,
sex
ratio,
or
fetal
weight.
At
120
mg/
kg,
maternal
body
weight
gain
during
GD
6­
10
was
decreased
(
p<=
0.01)
to
­
0.08
kg
compared
to
0.02
kg
in
the
controls.
Food
consumption
was
decreased
(
decr.
41%;
p<=
0.05)
on
GD
7
only.
Additionally
in
this
dose
group,
minor
decreases
(
p<=
0.05)
in
placental
weights
(
decr.
14%)
and
fetal
body
weights
(
decr.
7%)
were
observed.
The
maternal
LOAEL
is
120
mg/
kg/
day
based
on
minor
decreases
in
initial
body
weight
gains,
placental
weights,
and
fetal
weights
and
on
initialdecreased
food
consumption.
The
maternal
NOAEL
is
50
mg/
kg/
day
Dose­
related
increases
(
p<=
0.05)
in
fetal
incidences
of
the
following
skeletal
findings
were
observed
at
50
and
120
mg/
kg/
day:
(
i)
incomplete
ossification
of
the
pelvis
pubes;
(
ii)
irregular
spinous
process
on
the
scapulae;
(
iii)
incomplete
ossification
of
the
anterior
phalanges;
and
(
iv)
incomplete
ossification
of
the
posterior
phalanges.
Litter
incidences
were
significant
(
p<=
0.01)
at
50
and
120
mg/
kg
for
the
irregular
spinous
process
on
the
scapulae
but
only
at
120
mg/
kg
for
the
incomplete
ossification
of
the
pubis
bone
of
the
pelvis
and
posterior
phalanges.
Litter
incidences
of
incomplete
ossification
of
the
anterior
phalanges
were
not
significant.
Additionally
at
120
mg/
kg,
increased
incidences
of
the
following
skeletal
findings
were
observed:
(
i)
fused,
missing,
abnormal,
and/
or
malpositioned
arches
and/
or
centra
of
the
caudal
vertebrae;
(
ii)
incomplete
ossification
and/
or
non­
ossification
of
the
skull,
sternebrae,
posterior
talus,
posterior
phalanges;
(
iii)
enlarged
fontanelle
in
the
skull;
and
(
iv)
extra
ribs.
The
developmental
LOAEL
is
50
mg/
kg/
day
based
on
dose­
related
increases
in
the
incidences
of
incomplete
ossification
of
the
pelvis
pubes
and
anterior
and
posterior
phalanges
and
irregular
spinous
processes
on
the
scapula.
The
developmental
NOAEL
is
20
mg/
kg/
day.

4.2.3
Reproductive
Toxicity
Multi­
Generation
Reproduction:
In
a
multi­
generation
reproductive
toxicity
study
(
MRID
00032541),
Bayleton
(
triadimefon,
purity
not
reported;
Lot/
batch
#
16002/
75)
was
administered
continuously
in
the
diet
to
SPF
Wistar
W.
74
rats
(
10
males:
20
females/
dose)
at
Page
37
of
105
nominal
dose
levels
of
0,
50,
300,
or
1800
ppm
(
0,
2.5,
15,
and
90
mg/
kg/
day).
The
P
animals
were
given
test
article
diet
formulations
for
approximately
100
days
prior
to
mating
to
produce
the
F
1a
litters.
After
weaning,
F
1a
animals
were
sacrificed,
and
a
second
mating
of
the
P
animals
was
conducted
to
produce
the
F
1b
litters.
After
weaning,
10
males:
20
females/
dose
from
the
F
1b
litters
were
selected
to
become
the
parents
of
the
F
2
generation
and
were
given
the
same
concentration
test
formulation
as
their
dam
for
approximately
4
weeks
prior
to
mating.
After
weaning,
F
2a
animals
were
sacrificed,
and
a
second
mating
of
the
F
1b
animals
was
conducted
to
produce
the
F
2b
litters.
This
process
was
repeated
for
a
total
of
three
generations.
The
final
generation
(
F
3b
)
was
sacrificed
at
the
end
of
lactation.
\

At
90
mg/
kg/
day,
fertility
was
affected
in
all
generations.
In
the
P
generation,
no
differences
occurred
in
the
fertility
index
during
the
first
mating;
however,
during
the
second
mating
the
fertility
index
was
decreased
compared
to
controls
(
17/
20
treated
vs.
19/
20
controls,
not
statistically
significant).
Fertility
values
were
significantly
(
p<
0.05)
lower
in
both
matings
of
the
F
1
generation.
Only
one
female
became
pregnant
in
the
F
2a
mating;
no
females
became
pregnant
in
the
F
2b
mating.
Therefore,
mating
of
the
F
1
generation
resulted
in
no
F
2
pups.
The
number
of
offspring
per
dam
at
birth
was
decreased
(
p<
0.05)
in
the
first
litters
of
both
the
P
generation
and
the
F
1
generation
(
decr.
16%
each).
As
a
result
of
low
fertility,
there
were
no
animals
in
the
90
mg/
kg/
day
group
of
the
F
2
generation
to
evaluate.
Additionally
at
90
mg/
kg/
day,
body
weights
of
the
P
generation
parents
were
decreased
(
decr.
approximately
15%;
p<
0.01)
during
F
1b
premating
mating,
gestation,
and
lactation.
Body
weight
gains
of
the
F
1
generation
parental
males
and
females
were
decreased
(
p<
0.01)
throughout
pre­
mating,
gestation,
and
lactation
for
both
matings.
No
treatment­
related
findings
were
noted
at
2.5
or
15
mg/
kg/
day.
The
LOAEL
for
reproductive
toxicity
is
90
mg/
kg/
day
based
on
decreased
fertility,
body
weights,
body
weight
gains,
and
litter
size.
The
NOAEL
is
15
mg/
kg/
day.
Due
to
low
fertility
in
the
90
mg/
kg/
day
parental
generations,
only
one
F
2
litter
and
no
F
3
litters
were
produced
at
this
dose.

In
the
F
1
pups,
at
90
mg/
kg/
day,
the
number
of
offspring
per
dam
was
decreased
(
p<
0.05)
in
the
F
1a
and
F
1b
litters
(
decr.
20­
31%)
at
post­
natal
day
(
PND)
5.
At
PND
28,
viability
was
decreased
(
p<
0.01)
in
the
F
1a
(
90.7%
treated
vs
97.8%
controls)
and
F
1b
(
56.4%
treated
vs
84.2%
controls)
pups.
Additionally,
body
weight
gains
of
the
F
1a
pups
were
decreased
(
decr.
10%;
p<
0.05)
during
lactation.
At
15
mg/
kg/
day,
body
weight
gains
of
the
F
2b
pups
were
decreased
(
decr.
15%;
p<
0.05)
during
PNDs
5,
7,
14,
and
21.
Body
weight
gains
were
also
decreased
(
decr.
10%;
p<
0.05)
in
the
F
3b
pups
at
PND
28.
The
LOAEL
and
NOAEL
for
offspring
toxicity
is
equivocal
due
to
severe
reproductive
effects.

Based
on
the
combined
two
studies
the
Parental
systemic/
Reproductive
toxicity
NOAEL
is
15
mg/
kg/
day
and
the
LOAEL
is
90
mg/
kg/
day.
The
Offspring
NOAEL
is
15
mg/
kg/
day
and
the
LOAEL
is
90
mg/
kg/
day.

This
study
was
classified
as
acceptable/
nonguideline
to
be
used
in
conjunction
with
the
3­
generation
reproduction
study
(
MRID
Page
38
of
105
Two­
Generation
Reproduction:
In
a
two­
generation
reproductive
toxicity
study
(
MRID
00155075),
Bayleton
(
triadimefon
92.6%
a.
i.;
Lot/
batch
#
not
provided)
was
administered
continuously
in
the
diet
to
bor:
wisw
(
SPF/
Cpb)
rats
(
10
males:
20
females/
dose)
at
nominal
dose
levels
of
0,
2.5,
or
90
mg/
kg/
day.
The
P
animals
were
given
test
article
diet
formulations
from
100
days
prior
to
mating
to
produce
the
F
1
generation.
After
weaning,
F
1
animals
were
selected
(
10
males:
20
females/
dose)
to
become
the
F
1
parents
of
the
F
2
generation
and
were
given
the
same
concentration
test
formulation
as
their
dam;
the
P
animals
were
sacrificed.
Treatment
of
the
F
1
animals
followed
the
same
pattern
as
the
P
animals;
however,
only
the
2.5
mg/
kg/
day
F
1
parents
were
sacrificed
when
the
F
2
litters
were
weaned.
The
treatment
of
the
F
1
90
mg/
kg/
day
groups
was
stopped;
the
90
mg/
kg/
day
F
1
males
were
mated
with
the
control
F
1
females,
while
the
90
mg/
kg/
day
F
1
females
were
mated
with
control
F
1
males.
This
cross­
mating
procedure
produced
a
second
F
2
litter
and
was
intended
to
provide
further
information
regarding
the
fertility
of
the
F
1
parents.
For
all
matings,
the
day
that
sperm
was
detected
in
a
vaginal
smear
was
designated
as
gestation
day
(
GD)
0.
No
parental
mortalities
occurred.
Sperm
motility,
sperm
morphology,
gestation
length,
and
sex
ratios
were
unaffected
by
treatment.

At
2.5
mg/
kg/
day,
body
weights
were
decreased
(
p<
0.01)
in
the
F
1
dams
on
GD
1,
6,
and
15
(
decr.
6­
7%).
Absolute
and
relative
(
to
body
weight)
ovary
weights
were
increased
(
incr.
10­
11%;
p<
0.05)
in
the
P
dams
(
organ
weights
were
not
determined
for
the
F
1
adults).
The
biological
significance
of
these
findings
is
considered
to
be
equivocal.
A
NOAEL
for
parental/
reproductive
toxicity
was
not
established
because
of
the
equivocal
findings
on
body
weights
in
the
F
1
dams
and
ovary
weights
in
the
P
dams
at
2.5
mg/
kg/
day.

At
90
mg/
kg/
day,
fertility
was
decreased
(
35%
treated
vs
85%
controls;
p<
0.01)
in
the
F
1
parents.
This
resulted
in
decreases
in
the
total
number
of
litters
(
7
treated
vs
17
controls)
and
the
total
number
of
pups
(
37
treated
vs
196
controls).
In
the
F
1
cross­
mating,
fertility
was
47.4%
from
the
mating
of
90
mg/
kg/
day
males
with
the
control
females
and
80%
from
the
mating
of
the
90
mg/
kg/
day
females
with
the
control
males.
In
the
absence
of
sperm
abnormalities,
it
was
concluded
that
the
observed
decrease
in
fertility
was
due
to
a
decreased
interest
of
the
males
incopulation.
Copulation
was
not
observed
in
6/
10
of
the
90
mg/
kg/
day
males
during
the
3­
week
cross­
mating
with
control
females.
Additionally
at
90
mg/
kg/
day,
body
weights
were
decreased
(
p<
0.05)
in
the
P
males
during
weeks
4,
5,
and
6;
in
the
P
females
during
weeks
1­
16
and
21­
26;
and
in
the
F
1
parental
males
and
females
during
weeks
9­
40.
Terminal
body
weights
were
decreased
(
decr.
12%;
p<
0.01)
in
the
P
females.
Absolute
and
relative
(
to
body
weight)
liver
weights
were
increased
(
incr.
23­
39%;
p<
0.01)
in
the
P
males
and
females.

At
90
mg/
kg/
day,
body
weights
were
decreased
(
p<
0.05)
at
birth
(
decr.
12­
13%)
and
lactation
in
the
F
1
and
F
2
pups.
Viability
was
decreased
(
p<
0.05)
in
the
F
1
pups
during
post­
natal
days
(
PNDs)
0­
5
(
51.4%
treated
vs
87.1%
controls)
and
PND
5­
28
(
79.2%
treated
vs
93.1%
controls)
and
in
the
F
2
pups
during
post­
natal
days
(
PNDs)
0­
5
(
37.8%
treated
vs
92.9%
controls)
and
PND
5­
28
(
71.4%
treated
vs
89.7%
controls).
Additionally,
litter
size
was
decreased
(
p<
0.01)
in
the
F
2
pups
(
5.3
treated
vs
11.5
controls).
The
LOAEL
for
offspring
toxicity
is
90
mg/
kg/
day
Page
39
of
105
based
on
decreased
pup
weights
and
viability
in
the
F
1
and
F
2
generations
and
decreased
litter
size
in
the
F
2
generation.
The
NOAEL
is
2.5
mg/
kg/
day.

Based
on
the
combined
two
studies
the
Parental
systemic/
Reproductive
toxicity
NOAEL
is
15
mg/
kg/
day
and
the
LOAEL
is
90
mg/
kg/
day.
The
Offspring
NOAEL
is
15
mg/
kg/
day
and
the
LOAEL
is
90
mg/
kg/
day.

This
study
is
classified
as
acceptable/
nonguideline
to
be
used
in
conjunction
with
multigeneration
reproduction
study
(
MRID
00032541).

4.2.4
Pre­
and/
or
Postnatal
Toxicity
There
was
no
evidence
for
quantitative
and
qualitative
susceptibility
following
oral
exposures
to
rats
in
utero.
However,
there
was
an
increase
susceptibility
following
oral
exposure
to
rabbits
in
utero.
The
degree
of
concern
for
pre­
and/
or
post­
natal
susceptibility
is
low
because
the
rabbit
NOAEL
(
20
mg/
kg/
day)
is
adequate
due
to
dose
spacing.
The
endpoint
used
for
risk
assessment
purposes
(
NOAEL
of
3.4
mg/
kg/
day
from
the
subchronic
neurotoxicity
study)
is
10x
lower
than
the
rabbit
NOAEL
and
it
is
accounted
for
in
the
overall
FQPA
database
uncertainty
factor
10x
for
the
lack
of
a
DNT.

4.2.5.
Recommendation
for
a
Developmental
Neurotoxicity
Study
The
mode
of
toxic
action
for
triadimefon
involves
blocking
the
reuptake
of
dopamine.
These
pesticides
act
as
indirect
dopamine
agonists
by
binding
to
the
dopamine
transporter
and
increasing
levels
of
synaptic
dopamine.
The
toxicological
impact
of
blocking
this
reuptake
following
exposure
to
triadimefon
during
development
is
not
know.
A
developmental
neurotoxicity
study
with
triadimefon
is
required
at
this
time.

Further
justification
for
this
study
is
provided
by
the
conclusions
of
an
expert
panel
(
Golub
et
al,
2005)
who
recently
reviewed
the
developmental
and
reproductive
toxicity
potential
of
methylphenidate.
This
panel
concluded
that
there
was
insufficient
evidence
to
evaluate
the
potential
developmental
neurotoxicity
of
this
human
drug
and
listed
developmental
neurotoxicity
and
pharmacokinetic
data
during
gestation
and
lactation
as
important
data
needs
for
methylphenidate.

4.3
Special
FQPA
Safety
Factor
Based
on
the
above
data,
the
special
FQPA
safety
factor
of
10x
is
not
required
since
the
current
developmental
and
reproductive
toxicity
studies
do
not
suggest
that
the
young
are
more
sensitive
than
adult
animals,
and
the
lack
of
DNT
is
addressed
by
the
FQPA
database
uncertainty
factor
of
10x.
Therefore,
the
FQPA
Safety
Factor
is
1.
Page
40
of
105
4.4
Hazard
Identification
and
Toxicity
Endpoint
Selection
4.4.1
Acute
Reference
Dose
(
aRfD)

The
subchronic
neurotoxicity
study
in
rats
(
MRID
44153501)
was
chosen
for
the
aRfD.
Triadimefon
technical
(
95.8­
95.9%
a.
i.)
was
administered
in
the
diet
to
18
Wistar
rats/
sex/
dose
at
levels
of
0,
50,
800,
or
2,200
ppm
(
0,
3.4,
54.6
and
149.8
mg/
kg/
day
for
males
and
0,
4.3,
68.7,
and
189.7
mg/
kg/
day
for
females)
for
13­
weeks.
Six
rats/
sex/
dose
level
were
subjected
to
neuropathological
evaluations
at
the
end
of
the
exposure
period
and
the
remaining
12
rats/
sex/
dose
level
were
observed
for
another
4
(
males)
or
10
(
females)
weeks
to
investigate
the
persistence
of
the
toxicological
effects.

At
800
ppm
there
were
increases
in
rearing
(
both
sexes),
and
motor
and
locomotor
activity
(
females
only)
and
other
indications
of
hyperactivity
especially
in
females.
This
indication
of
hyperactivity
include
clinical
signs
(
motility,
digging,
spilling
food
and
water);
body
weight
and
body
weight
gain
(
9%
%
and
14%
&)
were
also
decreased
in
both
sexes
in
the
initial
four
weeks
of
dosing.
There
were
also
slight
(
not
significant)
increases
in
male
brain
relative
weight
and
grip
strength.

At
2200
ppm
there
was
stereotypy
(
pacing
only
in
a
few
rats),
relative
brain
weight
(
18%
both
sexes)
and
increased
frequency
and
intensity
of
the
symptoms
noted
at
800
ppm.
Increased
landing
foot
splay
and
grip
strength
(
believed
to
be
associated
with
the
decrease
in
body
weight)
were
evident.
The
effects
were
considered
slowly
reversible
since
body
weight
recovered
slowly
and
there
was
some
evidence
of
hyperactivity
persisting.
The
LOAEL
for
neurotoxicity
was
800
ppm
(
54.6%
and
68.7&
mg/
kg/
day)
based
largely
on
hyperactivity.
The
NOAEL
is
50
ppm
(
3.4%
and
4.3&
mg/
kg/
day).

For
the
acute
dietary
risk
assessment,
the
Uncertainty
Factor
(
UF)
is
:
1,000x
(
10
x
for
interspecies
extrapolation,
10x
for
intraspecies
variations
and
10x
for
FQPA
database
uncertainty
(
lack
of
developmental
neurotoxicity
study).

Acute
Reference
Dose
(
aRfD)
3.4
mg/
kg/
day
(
NOAEL)
=
0.0034
mg/
kg/
day
1,000
(
UF)

The
subchronic
neurotoxicity
study
(
SCN)
was
used
to
established
the
acute
reference
dose
aRfD),
although
an
acceptable
acute
neurotoxicity
study
(
ACN)
is
available.
The
endpoint
of
concern
is
neurotoxicity
seen
both
after
acute
gavage
and
repeated
dietary
exposure.
The
clinical
signs
include
increase
rearing,
motor
activity,
stereotypy,
and
self
mutilation.
It
is
noted
that
the
ACN
NOAEL
of
2
mg/
kg/
day
is
lower
than
the
3.4
NOAEL
in
the
SCN
selected
for
the
overall
risk
assessment.
The
NOAEL
of
the
ACN
study
is
an
artifact
of
dose
selection.

Again,
the
Agency
notes
that
the
dose
spacing
between
the
NOAEL
and
LOAELs
in
the
guideline
Page
41
of
105
acute
and
subchronic
neurotoxicity
studies
are
fairly
large
(>
10­
fold).
This
large
dose
spacing
may
contribute
to
the
conservative
nature
of
the
current
risk
assessment.
As
the
Agency
refines
its
preliminary
risk
assessment
for
triadimefon
in
the
coming
months,
dose­
response
studies
from
the
literature
may
provide
additional
information
for
the
hazard
characterization
of
triadimefon.

4.4.2
Chronic
Reference
Dose
(
cRfD)

The
subchronic
neurotoxicity
study
in
rats
(
MRID
44153501)
was
chosen
for
the
cRfD.
Please
see
Section
4.4.1.

For
the
chronic
dietary
risk
assessment,
the
Uncertainty
Factor
(
UF)
is:
1000x
(
10
x
for
interspecies
extrapolation,
10x
for
intraspecies
variations
and
10x
for
database
uncertainty
(
lack
of
developmental
neurotoxicity
study).

Chronic
Reference
Dose
(
cRfD)
3.4
mg/
kg/
day
(
NOAEL)
=
0.0034
mg/
kg/
day
1,000
(
UF)

Using
the
subchronic
neurotoxicity
study
accounts
for
the
most
sensitive
species
and
endpoints
(
rat
vs.
chronic
dog
study
MRID
00032539).
An
extra
factor
will
not
be
used
for
using
a
shortterm
factor
(
SCN)
in
a
long­
term
risk
assessment
because
the
NOAELs
available
for
the
longterm
studies
(
repro
(
MRIDs
00155075
and
00032541)
and
chronic
(
MRID
00032539)
are
higher
than
the
NOAEL
selected
for
this
risk
assessment
(
10
­
15
mg/
kg/
day
vs.
3.4
mg/
kg/
day).

4.4.3
Incidental
Oral
Exposure
(
Short­
and
Intermediate
­
Term)

The
subchronic
neurotoxicity
study
in
rats
(
MRID
44153501)
is
chosen
for
the
short
and
intermediate
incidental
oral
exposure.
Please
see
Section
4.4.1.

Dosage
used
in
this
study
were
0,
50,
800,
or
2,200
ppm
(
0,
3.4,
54.6
and
149.8
mg/
kg/
day
for
males
and
0,
4.3,
68.7,
and
189.7
mg/
kg/
day
for
females)
for
13­
weeks.
The
LOAEL
for
neurotoxicity
is
800
ppm
(
54.6%
and
68.7&
mg/
kg/
day)
based
largely
on
hyperactivity.
The
NOAEL
is
50
ppm
(
3.4%
and
4.3&
mg/
kg/
day).

The
SCN
study
covers
the
appropriate
duration.
Further
justification
for
selection
of
this
endpoint
for
the
incidental
oral
exposure
is
that
the
effects
seen
in
the
selected
study
were
also
observed
in
other
studies
(
acute
neurotoxicity
and
developmental)
with
triadimefon.
Based
on
the
database
for
triadimefon,
the
CNS
is
considered
as
the
target
organ
and
hyperactivity
was
also
seen
in
the
21
day
dermal
toxicity
(
MRID
42341501)
and
developmental
toxicity
(
MRID
00089023)
studies.

4.4.4
Dermal
Exposure
(
Short­,
and
Intermediate­
Term)
Page
42
of
105
The
21­
day
dermal
toxicity
study
(
MRID
42341501)
in
rats
was
chosen
as
the
basis
for
shortand
intermediate­
term
dermal
exposure.
In
the
21­
day
dermal
toxicity
study
(
MRID
42341501),
triadimefon
(
95.9%
a.
i.)
moistened
with
tap
water,
was
applied
to
the
shaved
intact
skin
of
5
Sprague­
Dawley
[
Sas:
CD(
SD)
BR]
rats/
sex/
dose
at
dose
levels
of
0,
100,
300,
or
1,000
mg/
kg
bw/
day,
6
hours/
day
for
5
days/
week
over
a
21
day
period
for
a
total
of
15
applications.
No
compound­
related
effects
on
mortality,
body
weight,
body
weight
gain,
food
consumption,
hematology,
clinical
chemistry,
absolute
or
relative
(
to
body)
organ
weight,
or
gross
pathological
data
were
observed
at
any
dose
level
in
either
sex.
There
were
no
signs
of
dermal
irritation
at
any
dose.

At
1,000
mg/
kg
(
limit
dose)
increased
reactivity
was
observed
in
5/
5
females
on
Days
11­
18
and
increased
activity
was
observed
in
1/
5
females
on
Days
9­
11
and
14.
These
clinical
signs
are
consistent
with
the
well­
established
behavioral
effects
associated
with
this
test
substance.
In
addition,
minimal
to
slight
diffuse
acanthosis
was
present
in
the
treated
skin
of
2/
5
females
and
one
of
these
females
also
displayed
slight
hypertrophy
of
the
sebaceous
glands;
although
these
findings
are
possibly
treatment­
related,
they
are
considered
not
to
be
toxicologically
significant.
The
LOAEL
was
1,000
mg/
kg/
day
based
on
increased
reactivity
and
activity
in
the
females.
The
NOAEL
is
300
mg/
kg/
day.

This
study
covers
the
appropriate
durations
for
short
and
intermediate
time
intervals.
The
use
of
the
dermal
toxicity
study
for
the
short
and
intermediate
term
risk
assessment
is
that
the
primary
toxicity
of
concern
(
neurotoxicity)
was
demonstrated
via
the
dermal
route.

4.4.5
Inhalation
Exposure
(
Short­
and
Intermediate­
Term)

In
the
absence
of
a
repeated
inhalation
exposure
study,
the
subchronic
neurotoxicity
study
in
rats
(
MRID
44153501)
was
chosen
for
short
­
and
intermediate­
term
inhalation
exposure.
Please
see
section
4.4.1.

Dosage
used
in
this
study
were
0,
50,
800,
or
2,200
ppm
(
0,
3.4,
54.6
and
149.8
mg/
kg/
day
for
males
and
0,
4.3,
68.7,
and
189.7
mg/
kg/
day
for
females)
for
13­
weeks.
The
LOAEL
for
neurotoxicity
is
800
ppm
(
54.6%
and
68.7&
mg/
kg/
day)
based
largely
on
hyperactivity.
The
NOAEL
is
50
ppm
(
3.4%
and
4.3&
mg/
kg/
day).

The
study
covers
the
appropriate
durations
for
short
and
intermediate
time
intervals.
Absorption
via
the
inhalation
route
is
presumed
to
be
equivalent
to
oral
absorption
(
inhalation
absorption
rate
=
100%).

4.4.6
Table
4.3
Margins
of
Exposure
Page
43
of
105
Route
Duration
Short­
Term
(
1­
30
Days)
Intermediate­
Term
(
1
­
6
Months)
Long­
Term
(>
6
Months)

Residential
Exposure
Dermal
1,000
1,000
Not
Applicable
Inhalation
1,000
1,000
Not
Applicable
Occupational
(
Worker)
Exposure
Dermal
100
100
Not
Applicable
Inhalation
100
100
Not
Applicable
A
Margin
of
Exposure
of
1,000
is
required
for
residential
exposure
to
triadimefon,
(
10
x
for
interspecies
extrapolation,
10
x
for
intraspecies
variability
and
10x
for
FQPA
database
uncertainty
(
lack
of
developmental
neurotoxicity
study).
A
Margin
of
Exposure
of
100
is
required
for
occupational
(
pesticide
handlers)
exposure
to
triadimefon,
(
10
x
for
interspecies
extrapolation
and
10
x
for
intraspecies
variability).

4.4.7
Recommendation
for
Aggregate
Exposure
Risk
Assessment
Combining
Exposure
for
Occupational
Assessment:
Inhalation
and
dermal
exposure
should
be
combined
for
occupational
risk
assessment
because
the
endpoint
(
neurotoxicity)
is
the
same
for
both
routes.

4.4.8
Classification
of
Carcinogenic
Potential
In
accordance
with
the
EPA
Draft
Guidelines
for
Carcinogen
Risk
Assessment
(
July
1999),
the
Cancer
Assessment
Review
Committee
(
CARC)
classified
triadimefon
into
category
C
"
possible
human
carcinogen."
This
classification
is
based
on
a
statistically
significant
increase
in
thyroid
adenomas
in
male
Wistar
rats
and
statistically
significant
increases
in
hepatocellular
adenomas
in
both
sexes
of
the
NMRI
mouse.
However,
it
was
concluded
that
a
quantified
carcinogenic
risk
assessment
for
triadimefon
is
not
appropriate
and
risk
assessment
will
be
based
on
the
cPAD
and
Margin
of
Exposure
approach
only.

The
following
table
(
4.4)
summarizes
the
studies,
endpoints,
dose
levels,
and
uncertainty/
safety
Page
44
of
105
factors
selected
for
the
assessment
of
dietary,
oral,
dermal,
and
inhalation
exposure
to
triadimefon.
Note
that
the
aPAD
and
cPAD
are
based
on
the
standard
acute
and
chronic
reference
dose,
divided
by
the
FQPA
Safety
Factor
(
which
in
this
case
is
1).
All
other
risk
estimates
are
expressed
as
a
Margin
of
Exposure
(
the
ratio
of
exposure
to
the
NOAEL
or
LOAEL).

Table
4.4
Summary
of
Toxicological
Doses
and
Endpoints
for
Triadimefon
Exposure
Scenario
Dose
Used
in
Risk
Assessment,
UF
Special
FQPA
SF*
and
Level
of
Concern
for
Risk
Assessment
Study
and
Toxicological
Effects
Acute
Dietary
(
general
population)
NOAEL
=
3.4
mg/
kg/
day
UF
=
1000
Acute
RfD
=
0.0034
mg/
kg/
day
FQPA
SF
=
1X
aPAD
=
acute
RfD
FQPA
SF
aPAD
=
0.0034
mg/
kg/
day
Subchronic
neurotoxicity
study
in
rats.
LOAEL
=
54.6/
68.7
mg/
kg/
day
based
largely
on
hyperactivity.

Chronic
Dietary
(
all
populations)
NOAEL
=
3.4
mg/
kg/
day
UF
=
1000
Chronic
RfD
=
0.0034
mg/
kg/
day
FQPA
SF
=
1X
PAD
=
chronic
RfD
FQPA
SF
cPAD
=
0.0034
mg/
kg/
day
Subchronic
neurotoxicity
study
in
rats.
LOAEL
=
54.6/
68.7
mg/
kg/
day
based
largely
on
hyperactivity.

Incidental
Oral
Short­
Term
(
1
­
30
days)
NOAEL
=
3.4
mg/
kg/
day
UF
=
1000
Residential
MOE
=
1000
Subchronic
neurotoxicity
study
in
rats.
LOAEL
=
54.6/
68.7
mg/
kg/
day
based
largely
on
hyperactivity.

Incidental
Oral
Intermediate­
Term
(
1
­
6
months)
NOAEL
=
3.4
mg/
kg/
day
UF
=
1000
Residential
MOE
=
1000
Subchronic
neurotoxicity
study
in
rats.
LOAEL
=
54.6/
68.7
mg/
kg/
day
based
largely
on
hyperactivity.

Dermal
Short­
Term
(
1
­
30
days)
Dermal
NOAEL
=
300
mg/
kg/
day
Residential
MOE
=
1000
Occupational
MOE
=
100
21
Day
Dermal
Toxicity
in
rabbits.
The
LOAEL=
1000
mg/
kg/
day
based
on
increased
reactivity
and
activity
in
the
females.

Dermal
Intermediate­
Term
(
1
­
6
months)
Dermal
NOAEL
=
300
mg/
kg/
day
Residential
MOE
=
1000
Occupational
MOE
=
100
21
Day
Dermal
Toxicity
in
rabbits.
The
LOAEL=
1000
mg/
kg/
day
based
on
increased
reactivity
and
activity
in
the
females.
Table
4.4
Summary
of
Toxicological
Doses
and
Endpoints
for
Triadimefon
Exposure
Scenario
Dose
Used
in
Risk
Assessment,
UF
Special
FQPA
SF*
and
Level
of
Concern
for
Risk
Assessment
Study
and
Toxicological
Effects
Page
45
of
105
Dermal
Long­
Term
(>
6
months)
Not
Applicable
Not
Applicable
Quantitative
risk
assessment
is
not
required
since
no
long­
term
dermal
exposure
is
expected.

Inhalation
Short­
Term
(
1
­
30
days)
NOAEL
=
3.4
mg/
kg/
day
(
Inhalation
absorption
rate
=
100%)
Residential
MOE
=
1000
Occupational
MOE
=
100
Subchronic
neurotoxicity
study
in
rats.
LOAEL
=
54.6/
68.7
mg/
kg/
day
based
largely
on
hyperactivity.

Inhalation
Intermediate­
Term
(
1
­
6
months)
NOAEL
=
3.4
mg/
kg/
day
(
Inhalation
absorption
rate
=
100%)
Residential
MOE
=
1000
Occupational
MOE
=
100
Subchronic
neurotoxicity
study
in
rats.
LOAEL
=
54.6/
68.7
mg/
kg/
day
based
largely
on
hyperactivity.

Inhalation
Long­
Term
(>
6
months)
Not
Applicable
Not
Applicable
Quantitative
risk
assessment
is
not
required
since
no
long­
term
exposure
is
expected.

Cancer
(
oral,
dermal,
inhalation)
Classification:
Category
C
"
possible
human
carcinogen"
based
on
statistically
significant
increase
in
thyroid
adenomas
in
male
Wistar
rats
and
statistically
significant
increases
in
hepatocellular
adenomas
in
both
sexes
of
the
NMRI
mouse.

UF
=
uncertainty
factor,
FQPA
SF
=
Special
FQPA
safety
factor,
NOAEL
=
no
observed
adverse
effect
level,
LOAEL
=
lowest
observed
adverse
effect
level,
PAD
=
population
adjusted
dose
(
a
=
acute,
c
=
chronic)
RfD
=
reference
dose,
MOE
=
margin
of
exposure,
LOC
=
level
of
concern,
NA
=
Not
Applicable
*
Refer
to
Section
4.5
4.5
Endocrine
Disruption
EPA
is
required
under
the
Federal
Food,
Drug,
and
Cosmetic
Act
(
FFDCA),
as
amended
by
FQPA,
to
develop
a
screening
program
to
determine
whether
certain
substances
(
including
all
pesticide
active
and
other
ingredients)
"
may
have
an
effect
in
humans
that
is
similar
to
an
effect
produced
by
a
naturally
occurring
estrogen,
or
other
such
endocrine
effects
as
the
Administrator
may
designate."
Following
recommendations
of
its
Endocrine
Disruptor
and
Testing
Advisory
Committee
(
EDSTAC),
EPA
determined
that
there
was
scientific
bases
for
including,
as
part
of
the
program,
the
androgen
and
thyroid
hormone
systems,
in
addition
to
the
estrogen
hormone
system.
EPA
also
adopted
EDSTAC's
recommendation
that
the
Program
include
evaluations
of
potential
effects
in
wildlife.
For
pesticide
chemicals,
EPA
will
use
FIFRA
and,
to
the
extent
that
effects
in
wildlife
may
help
determine
whether
a
substance
may
have
an
effect
in
humans,
FFDCA
authority
to
require
the
wildlife
evaluations.
As
the
science
develops
and
resources
allow,
screening
of
additional
hormone
systems
may
be
added
to
the
Endocrine
Disruptor
Screening
Program
(
EDSP).
Page
46
of
105
5.0
DIETARY
EXPOSURE
/
ASSESSMENT
5.1
Tolerances
/
Tolerance
Expression
Tolerances
are
established
for
residues
of
triadimefon
[
1­(
4­
chlorophenoxy)­
3,3­
dimethyl­
1­(
1H­
1,2,4­
triazol­
1­
yl)­
2­
butanone]
and
its
metabolites
containing
chlorophenoxy
and
triazole
moieties
(
expressed
as
the
parent
compound)
in/
on
various
plant
and
animal
commodities
[
40
CFR
§
180.410].
The
established
tolerances
for
residues
in
plant
and
animal
commodities
[
40
CFR
§
180.410(
a)]
range
from
0.04
ppm
(
milk,
hog,
and
poultry
commodities)
to
145
ppm
(
grass
seed
cleanings).
Time­
limited
Section
18
tolerances
(
now
expired)
were
established
for
residues
in/
on
artichokes,
asparagus,
and
chili
peppers
at
0.15
­
0.6
ppm
[
40
CFR
§
180.410(
b)].
A
tolerance
with
regional
registration
is
established
for
triadimefon
and
its
metabolites
in/
on
raspberries
at
2.0
ppm
[
40
CFR
§
180.410(
c)].

Residues
of
triadimenol
(
and
its
butanediol
metabolite),
from
use
of
triadimenol
per
se,
are
regulated
separately
under
40
CFR
§
180.450.
In
addition,
40
CFR
§
180.3(
d)(
13)
specifies
that
where
tolerances
are
established
for
residues
of
both
1­(
4­
chlorophenoxy)­
3,3­
dimethyl­
1­(
1H­
1,2,4­
triazole­
1­
yl)­
2­
butanone
(
triadimefon)
and
$­(
4­
chlorophenoxy)­"­(
1,1­
dimethylethyl)­
1H­
1,2,4­
triazole­
1­
ethanol
(
triadimenol)
including
its
butanediol
metabolite,
1­(
4­
chlorophenoxy)­
3,3­
dimethyl­
3­
hydroxymethyl­
1­(
1H­
1,2,4­
triazol­
1­
yl)­
2­
butanol,
in
or
on
the
same
raw
agricultural
commodity
and
its
products
thereof,
the
total
amount
of
such
residues
shall
not
yield
more
residue
than
that
permitted
by
the
higher
of
the
two
tolerances.
Currently,
triadimefon
and
triadimenol
do
not
share
any
uses,
so
40
CFR
§
180.3(
d)(
13)
should
be
deleted.

5.2
Analytical
Methods
Plant
Commodities:
Two
gas
chromatography
with
mass
spectrometry
detection
(
GC/
MS)
methods
are
listed
in
the
Pesticide
Analytical
Manual
(
PAM
Vol.
II)
for
enforcement
of
tolerances
in
plant
and
livestock
commodities.
The
methods
use
a
single
moiety
detection
in
which
residues
are
converted
to
p­
dichlorophenol,
derivatized
with
dinitrofluorobenzene,
and
reported
as
triadimefon
equivalents.
The
GC/
MS
method
is
no
longer
adequate
due
to
the
recommended
tolerance
expression
revisions.
However,
a
GC
method
using
a
nitrogen
phosphorus
detector
(
NPD;
Report
No.
80488)
is
available
for
determination
of
residues
of
triadimefon,
triadimenol,
KWG
1323,
and
KWG
1342
and
is
adequate
for
the
enforcement
of
apple,
grape,
pear,
pineapple,
and
raspberry
tolerances.
The
reported
method
limit
of
quantitation
(
LOQ)
is
0.01
ppm
for
each
analyte.
The
limit
of
detection
(
LOD)
was
not
reported.

Livestock
Commodities:
The
Pesticide
Analytical
Manual
(
PAM)
Vol.
II
lists
the
two
GC/
MS
methods
described
above
(
Methods
I
and
II)
for
the
determination
of
triadimefon
and
its
free
and
conjugated
metabolites
in
livestock
commodities.
Method
I
(
Report
No.
69531)
is
appropriate
for
livestock
tissues
and
milk
and
Method
II
(
Report
No.
80265)
is
appropriate
for
livestock
tissues
and
eggs.
The
reported
LOQ
is
0.05
and
the
LOD
is
0.01
ppm
for
both
Page
47
of
105
methods.

Multiresidue
Methods:
The
10/
99
FDA
PESTDATA
database
(
PAM
Volume
I,
Appendix
I)
indicates
that
triadimefon
is
completely
recovered
(>
80%)
using
Multiresidue
Methods
Section
302
(
Luke
Method;
Protocol
D);
recovery
of
triadimefon
is
small
(<
50%)
using
Multiresidue
Methods
Sections
303
(
Mills,
Onley,
and
Gaither;
Protocol
E,
nonfatty)
and
304
(
Mills,
fatty
food).
Triadimefon
metabolites
triadimenol
and
KWG
1323
are
completely
recovered
using
Section
302.
Triadimenol,
KWG
1323,
and
metabolite
KWG
1732
are
not
recovered
using
Sections
303
and
304.

5.3
Field
Trial
/
Feeding
Study
Residue
Data
Submitted
data
for
the
"
magnitude,"
or
amount
of
residue
in/
on
apples,
grapes,
pears,
pineapple,
and
raspberries
(
based
on
current
use
patterns)
are
adequate
for
reregistration.
However,
the
Agency
will
require
some
label
revisions
and/
or
tolerance
adjustments
for
those
commodities.
Use
of
triadimefon
on
the
cucurbit
vegetables
group,
grass
(
including
grass
grown
for
seed),
nectarines,
sugar
beets,
and
wheat,
is
not
supported
by
the
basic
producer,
and
these
commodities
will
be
removed
from
all
triadimefon
product
labels.
The
available
crop
field
trials
reflecting
use
of
registered
formulations
at
1x
the
maximum
label
rate
show
finite
residues
of
triadimefon
and
its
metabolites
triadimenol,
KWG
1342,
and
KWG
1323
in/
on
apples,
grapes,
pears,
and
pineapples
and
triadimefon
and
triadimenol
in/
on
raspberries.
Analysis
for
residues
of
the
metabolites
KWG
1342
and
KWG
1323
were
not
performed
in
the
raspberry
field
trials.

The
reregistration
requirements
for
data
depicting
the
magnitude
of
triadimefon
residues
of
concern
in
meat,
milk,
poultry,
and
eggs
have
been
fulfilled.
Acceptable
ruminant
and
poultry
feeding
studies
have
been
submitted
and
evaluated.
In
these
studies,
livestock
were
fed
a
1:
1
mixture
of
triadimefon
and
triadimenol.
Samples
were
analyzed
for
bound
and
free
residues
of
triadimefon,
triadimenol,
KWG
1342,
and
KWG
1323.

Triadimefon
is
not
registered
for
use
as
a
direct
livestock
treatment
and
the
supported
registered
uses
on
apples,
grapes,
pears,
pineapples,
and
raspberries
are
not
used,
in
general,
as
feed
items
except
for
some
use
of
apple
wet
pomace.
Based
on
feeding
study
data
for
ruminants
and
poultry,
and
residue
data
for
apple
wet
pomace,
HED
can
conclude
there
is
no
expectation
of
finite
residues
in
ruminant
commodities.
Therefore,
under
the
provisions
of
40
CFR
§
180.6(
a)(
3),
no
additional
data
on
the
transfer
of
residues
to
meat,
milk,
poultry,
and
eggs
are
required,
and
tolerances
for
livestock
commodities
should
be
revoked.
Also,
for
the
purposes
of
risk
assessment,
no
residues
are
expected
in
ruminant,
poultry,
or
swine
commodities.

5.4
Residue
in
Processed
Commodities
The
available
data
indicate
that
residues
do
not
concentrate
significantly
in
apple
juice
(
reduction
factor
of
0.6x),
grape
juice
or
pineapple
juice.
The
available
data
indicate
that
residues
of
Page
48
of
105
triadimefon
and
its
metabolites
concentrate
1.6x
in
apple
wet
pomace,
4x
in
raisins
and
1.3x
in
pineapple
process
residue
(
pineapple
bran).
The
available
data
also
indicate
that
triadimefon
residues
of
concern
concentrate
10x
in
apple
dry
pomace,
3x
in
grape
wet
pomace,
5x
in
grape
dry
pomace,
and
7x
in
raisin
waste,
and
1.3x
in
pineapple
process
residue
(
pineapple
bran).
However,
no
tolerances
are
required
for
these
commodities
as
they
are
no
longer
considered
significant
livestock
feed
items.
Of
the
food/
feed
uses
supported
for
reregistartion
(
apples,
pears,
grapes,
raspberries,
and
pineapple)
only
apples
have
processing
by­
products
that
are
commonly
used
as
livestock
feed
items;
apple
wet
pomace.
Also,
apple
wet
pomace
is
only
used,
in
any
significant
amount,
for
feeding
beef
cattle
(
since
dairy
producers,
in
general,
are
careful
to
avoid
residue­
bearing
feed
items).

5.5
Residue
in
Rotational
Crops
Because
triadimefon
and
its
regulated
metabolites
were
identified
at
>
0.01
ppm
in
various
rotational
crops
at
various
intervals,
limited
and/
or
field
rotational
crop
studies
were
required.
However,
since
the
registrant
has
requested
the
removal
of
all
rotatable
crop
uses
from
product
labels,
no
additional
data
concerning
confined/
field
accumulation
in
rotational
crops
is
required.

5.6
Tolerance
Reassessment
Tolerances
for
residues
in/
on
plant
and
livestock
commodities
have
been
established
under
40
CFR
§
180.410.
The
tolerances
are
expressed
in
terms
of
residues
of
triadimefon
[
1­(
4­
chlorophenoxy)­
3,3­
dimethyl­
1­(
1H­
1,2,4­
triazol­
1­
yl)­
2­
butanone]
and
its
metabolites
containing
chlorophenoxy
and
triazole
moieties
(
expressed
as
the
parent
compound).
The
qualitative
nature
of
the
residue
in
plants
and
livestock
is
adequately
understood.
HED
has
determined
that
the
triadimefon
residues
of
concern
in/
on
apples,
grapes,
pears,
pineapples,
and
raspberries
for
tolerance
expression
are
triadimefon
and
triadimenol.
The
reorganization
of
triadimefon
tolerances
and
tolerance
expression
for
all
RACs
should
be
conducted
as
depicted
below
in
Table
5.1.
A
summary
of
triadimefon
tolerance
reassessments
is
presented
in
Table
5.2.
Page
49
of
105
Table
5.1
Reorganization
of
Triadimefon
Tolerances
Required
Under
40
CFR.

40
CFR
Section
Reserved
For
Tolerance
Expression
§
180.410(
a)
apple,
grape,
pear,
and
pineapple
Tolerances
are
established
for
the
combined
residues
of
the
fungicide
1­(
4­
chlorophenoxy)­
3,3­
dimethyl­
1­(
1H­
1,2,4­
triazol­
1­
yl)­
2­
butanone
[
triadimefon]
and
$­(
4­
chlorophenoxy)­"­(
1,1­
dimethylethyl)­
1H­
1,2,4­
triazole­
1­
ethanol
[
triadimenol],
expressed
as
triadimefon,
in
or
on
the
following
raw
agricultural
commodities:

§
180.410(
c)
raspberry
Tolerances
with
regional
registration
are
established
for
the
combined
residues
of
the
fungicide
1­(
4­
chlorophenoxy)­
3,3­
dimethyl­
1­(
1H­
1,2,4­
triazol­
1­
yl)­
2­
butanone
[
triadimefon]
and
$­(
4­
chlorophenoxy)­"­(
1,1­
dimethylethyl)­
1H­
1,2,4­
triazole­
1­
ethanol
[
triadimenol],
expressed
as
triadimefon,
in
or
on
the
following
raw
agricultural
commodities:

The
available
data
indicate
that
residues
of
triadimefon
concentrate
4x
in
raisins.
Based
on
HAFT
residues
for
grapes
(<
0.62
ppm)
and
the
concentration
factor
for
raisins,
expected
triadimefon
residues
of
concern
in
raisins
are
2.5
ppm,
which
is
significantly
greater
than
the
reassessed
tolerance
for
the
RAC
(
1.0
ppm).
Therefore,
a
tolerance
of
2.5
ppm
must
be
proposed
for
residues
in
raisins.

Table
5.2
Tolerance
Reassessment
Summary
for
Triadimefon.

Commodity
Current
Tolerance
(
ppm)
Reassessed
Tolerance
(
ppm)
Comment
[
Correct
Commodity
Definition]

Tolerances
Established
Under
40
CFR
§
180.410(
a)

Apple
1
0.2
New
data
from
field
trails
show
lower
residues
are
expected.

Apple,
wet
pomace
and
Apple,
dry
pomace
4
Revoke
The
available
data
indicate
that
a
tolerance
for
wet
apple
pomace
is
not
required,
and
dry
apple
pomace
is
no
longer
considered
a
significant
livestock
feed
item.

Barley,
milled
fractions
(
except
flour)
4
Revoke
Currently,
Bayer
does
not
have
any
registered
uses
of
triadimefon
on
barley.
1
Beet,
sugar
0.5
Revoke
Currently,
Bayer
does
not
have
any
registered
uses
of
triadimefon
on
sugar
beets.
Beet,
sugar,
tops
3
Cattle,
fat
1
Revoke
40
CFR
§
180.6(
a)(
3)
Cattle,
meat
1
Revoke
Cattle,
meat
byproducts
1
Revoke
Table
5.2
Tolerance
Reassessment
Summary
for
Triadimefon.

Commodity
Current
Tolerance
(
ppm)
Reassessed
Tolerance
(
ppm)
Comment
[
Correct
Commodity
Definition]

Page
50
of
105
Chickpea,
seed
0.1
Revoke
Currently,
Bayer
does
not
have
any
registered
uses
of
triadimefon
on
chickpea
plants.

Cucurbits
0.3
Revoke
Bayer
does
not
intend
to
support
use
of
triadimefon
on
cucurbits.

Eggs
0.04
Revoke
Currently,
Bayer
does
not
have
any
registered
uses
of
triadimefon
on
any
poultry
feed
items.
40
CFR
§
180.6(
a)(
3)

Goat,
fat
1
Revoke
40
CFR
§
180.6(
a)(
3)
Goat,
meat
1
Revoke
Goat,
meat
byproducts
1
Revoke
Grape
1
1
No
change.

Grape,
wet
pomace
and
Grape,
dry
pomace
3
Revoke
No
longer
considered
significant
livestock
feed
items.
Grape,
raisin,
waste
7
Grass,
forage
0.2
Revoke
Currently,
Bayer
does
not
have
any
registered
uses
of
triadimefon
on
pasture
or
rangeland.
Grass,
seed
screenings
145
Grass,
straw,
grown
for
seed
105
Hog,
fat
0.04
Revoke
Currently,
Bayer
does
not
have
any
registered
uses
of
triadimefon
on
any
hog
feed
items.
40
CFR
§
180.6(
a)(
3)
Hog,
meat
0.04
Hog,
meat
byproducts
0.04
Horse,
fat
1
Revoke
40
CFR
§
180.6(
a)(
3)
Horse,
meat
1
Horse,
meat
byproducts
1
Milk
0.04
Revoke
40
CFR
§
180.6(
a)(
3)

Nectarine
4
Revoke
Currently,
Bayer
does
not
have
any
registered
uses
of
triadimefon
on
nectarine.

Pear
1
0.2
New
data
from
field
trails
show
lower
residues
are
expected.

Pineapple,
fresh
3
2
Reevaluation
of
data
from
field
trails
show
lower
residues
are
expected.
[
Pineapple]
Table
5.2
Tolerance
Reassessment
Summary
for
Triadimefon.

Commodity
Current
Tolerance
(
ppm)
Reassessed
Tolerance
(
ppm)
Comment
[
Correct
Commodity
Definition]

Page
51
of
105
Poultry,
fat
0.04
Revoke
Currently,
Bayer
does
not
have
any
registered
uses
of
triadimefon
on
any
poultry
feed
items.
40
CFR
§
180.6(
a)(
3)
Poultry,
meat
0.04
Poultry,
meat
byproducts
0.04
Sheep,
fat
1
Revoke
40
CFR
§
180.6(
a)(
3)
Sheep,
meat
1
Sheep,
meat
byproducts
1
Wheat,
forage
15
Revoke
Currently,
Bayer
does
not
have
any
registered
uses
of
triadimefon
on
wheat.
Wheat,
grain
1
Wheat,
milled
fractions
(
except
flour)
4
Wheat,
straw
5
Tolerances
To
Be
Proposed
Under
40
CFR
§
180.410(
a)

Grape,
raisin
None
established
2.5
Tolerances
Established
Under
40
CFR
§
180.410(
c)

Raspberry
2
2
No
change.

5.7
Residue
in
Drinking
Water
Triadimefon
transforms
into
triadimenol
in
the
natural
environment,
particularly
in
shallow
subsurface
soil
and
is
moderately
mobile
and
persistent.
Triadimefon
on
or
near
the
soil
surface
or
on
vegetation
may
be
subject
to
runoff
and/
or
erosion
into
surface
water
bodies
used
as
drinking
water
supplies.
Triadimefon
and
triadimenol
may
also
leach
into
groundwater
when
triadimefon
is
applied
in
areas
with
well­
drained
soil,
high
rainfall
(
and/
or
irrigation)
rates,
and
shallow
water
tables.
Once
it
reaches
groundwater,
triadimenol
is
likely
to
degrade
more
slowly
than
the
parent
compound.
Both
parent
and
degradate
are
stable
to
hydrolysis
and
have
fairly
long
half­
lives
in
soil
and
water.
Most
municipal
groundwater
supplies
are
obtained
from
deeper,
confined
aquifers
less
at
risk
of
contamination.
However,
shallow
private
wells
can
become
contaminated
in
sensitive
areas
where
triadimefon
is
used.

5.7.1
Surface
Water
The
triadimefon
surface
water
assessment
is
based
on
three
crop
scenarios:
Christmas
tree
use
in
Oregon,
use
on
apples
in
Pennsylvania,
and
use
on
Florida
turf.
These
scenarios
represent
Page
52
of
105
different
and
characteristic
U.
S.
regions
where
these
crops
are
commonly
grown.
These
particular
scenarios
were
also
chosen
because
they
have
the
highest
labeled
use
rates
and
are
expected
to
present
the
greatest
risks
to
drinking
water
supplies.

For
the
PRZM/
EXAMS
model,
some
initial
assumptions/
simplifications
were
made;
1)
total
residues
(
parent
triadimefon
plus
the
degradate
triadimenol)
are
treated
as
a
single
component
in
terms
of
fate
properties
(
half­
lives,
etc.),
with
most
of
the
parent
converting
to
the
degradate
of
concern
(
triadimenol)
which
is
generally
more
persistent
in
the
environment;
2)
for
total
residues,
an
application
depth
of
0
cm
is
assumed
to
reflect
surface
applications
(
in
this
case,
aerial
and
ground
spray);
3)
input
parameters
most
relevant
to
processes
that
occur
at
or
near
time
of
application
(
molecular
weight,
vapor
pressure,
solubility,
K
oc
,
and
photolysis)
are
used
to
reflect
the
characteristics
of
the
parent
alone
since
the
parent
is
the
predominant
form
available
at
the
surface
following
application,
and
these
values
are
nonetheless
very
close
to
those
for
triadimenol;
4)
other
inputs
that
are
relevant
to
transport,
fate,
and
persistence
of
compound
(
soil
and
water
half­
lives)
are
derived
from
characteristics
of
total
residues
(
parent
+
triadimenol);
and
5)
the
aerobic
soil
half­
life
for
total
residues
(
triadimefon
+
triadimenol)
was
determined
to
be
240
days
and
the
aerobic
aquatic
half­
life
for
total
residues
of
concern
is
480
days;
and
6)
a
default
Percent
Cropped
Area
(
PCA)
factor
of
0.87
(
87%)
has
been
applied
to
all
the
scenarios;
and
7)
other
degradates
(
e.
g.,
CPMT)
are
not
considered
here
because
there
is
insufficient
data
on
the
specific
rates
and
locales
of
formation
and
conditions
under
which
formation
occurs
to
evaluate
tertiary
degradates
as
part
of
total
triadimefon
residues
 
however,
based
on
current
information,
other
degradates
are
not
at
this
time
considered
to
be
essential
components
of
this
drinking
water
evaluation.

Note
that
the
Florida
turf
assessment
represents
an
upper­
bound
for
potential
concentrations
since
the
total
number
of
applications
allowed
annually
is
undefined
on
the
label
(
assessment
is
based
on
the
upper­
bound
assumption
of
26
applications
per
year).
In
addition,
the
FL
turf
scenario
was
also
run
with
a
limited
number
of
applications.
As
requested
by
Bayer
CropScience
(
personal
communication),
a
total
of
three
applications
per
year
at
the
maximum
application
rate
for
turf
grass
(
3.026
kg/
ha)
with
14­
day
intervals
was
utilized
for
a
PRZM­
EXAMS
modeling
run.
This
presumably
represents
a
more
`
typical'
use
pattern
for
turf
applications.
The
results
of
this
limited
application
run
are
presented
here
simply
as
a
"
what­
if"
scenario
for
comparison
with
the
same
scenario
using
the
maximum
potential
number
of
annual
applications
(
26).
Since
there
is
no
information
on
the
label
to
indicate
a
limit
of
three
applications
per
year,
results
from
this
scenario
should
be
used
strictly
as
a
comparison
to
the
other
turf
scenario
with
26
applications.

There
remain
some
uncertainties
that,
if
addressed,
could
help
predict
potential
drinking
water
concerns.
Specifically,
additional
studies
elucidating
some
of
the
fate
parameters
would
lead
to
a
higher
level
of
confidence
in
the
accuracy
of
model
predictions.
These
include:
aerobic
soil
metabolism
studies
 
there
is
currently
a
single
valid
study
on
which
the
aerobic
soil
half­
life
for
total
residues
(
triadimefon
+
triadimenol)
is
based;
aerobic
aquatic
metabolism
studies,
of
which
there
are
currently
none
(
2X
the
aerobic
soil
half­
life
is
used);
and
further
information
on
the
Page
53
of
105
behavior
and
characteristics
of
some
of
the
other
degradates,
such
as
CPMT
(
which
is
a
degradate
of
the
degradate
triadimenol).

Table
5.3
Drinking
Water
Expected
Concentrations
(
raw
surface
water)

Crop/
Location
Acute
Concentration
(
ppb)
Chronic
Concentration
(
ppb)

1
in
10
year
annual
mean
36­
year
overall
mean
Oregon
Xmas
Trees
5.82
2.08
1.5
Pennsylvania
Apple
9.08
2.28
1.26
Florida
Turf
348.3
146.7
98.13
Florida
Turf
*
100.8
24.98
13.05
*
Limited
number
of
turf
applications
(
3)
as
per
Bayer
communiqué
of
July
25,
2005
5.7.2
Groundwater
Modeling:
As
an
initial
screen,
the
concentrations
expected
in
ground
water
for
the
use
of
triadimefon
were
estimated
using
the
SCI­
GROW
model
(
Table
3).
For
the
purposes
of
ground
water
evaluation,
specifically,
to
determine
the
likely
"
worst­
case"
situation
for
shallow
private
wells
(
and/
or
baseflow
discharge),
SCI­
GROW
was
run
with
the
following
input
parameters
(
and
associated
justifications)
based
on
the
assumption
that
fate
input
parameters
(
values
used
in
model
runs)
reflect
total
residues
(
triadimefon
+
triadimenol).
The
turf
scenario
was
run
with
26
applications
(
potential
maximum
number
according
to
label)
and
3
applications
(
representing
a
more
`
typical'
usage,
according
to
a
communiqué
from
Bayer
CropScience
on
or
about
July
25,
2005).
See
above
(
surface
water
modeling)
for
method
of
determination
and
justifications.

Table
5.4
Estimated
Drinking
Water
Concentrations
/
Groundwater
Crop
Max.
Use
Rate
(
lb/
acre)
Max.
No.
of
Applications
Koc
Soil
Aerobic
Half­
life
(
days)
Expected
Concentrations
(
ppb)
Xmas
Trees
0.25
8
387
240
1.24
Apple
0.25
3
0.47
Turf
2.7
26
43.6
Turf
*
2.7
3*
5.04
Monitoring:
Ground
water
monitoring
studies
supplied
by
the
registrant
indicate
maximum
concentrations
of
total
triadimefon
residues
somewhat
lower
than
predicted
by
SCIGROW
but
nonetheless
of
similar
magnitude.
The
most
recent
studies
show
maximum
shallow
ground
water
concentrations
of
approximately
25
ppb
for
turf
application
in
New
Jersey
and
1.67
ppb
for
turf
application
in
California.
The
application
rate
for
both
studies
was
about
3
lb
a.
i./
acre
(
110%
of
max
single
application),
but
only
2
applications
total
were
applied,
30
days
apart
(~
6
Page
54
of
105
lb/
acre
altogether).
This
may
account
for
the
lower
EEC
numbers
compared
to
SCI­
GROW.

5.8
Dietary
(
Food
and
Water
Combined)
Exposure
/
Risk
Estimates
5.8.1
Dietary
Risk
/
Background
Dietary
risk
for
triadimefon
is
assessed
by
comparing
acute
(
one­
day)
and
chronic
dietary
exposure
estimates
(
in
mg/
kg/
day)
to
both
the
triadimefon
aPAD
and
cPAD,
with
dietary
risk
expressed
as
percents
of
the
aPAD
and
cPAD.
Dietary
risk
is
estimated
for
the
general
U.
S.
population
and
population
sub­
groups
defined
by
sex,
age,
region,
and
ethnicity.

Acute
and
chronic
dietary
exposure
assessments
were
conducted
using
the
Dietary
Exposure
Evaluation
Model
software
with
the
Food
Commodity
Intake
Database
(
DEEM­
FCID
 
,
Version
2.00
­
2.02),
which
incorporates
consumption
data
from
USDA's
Continuing
Surveys
of
Food
Intakes
by
Individuals
(
CSFII),
1994­
1996
and
1998.
The
1994­
96,
98
data
are
based
on
the
reported
consumption
of
more
than
20,000
individuals
over
two
non­
consecutive
survey
days.
Foods
"
as
consumed"
(
e.
g.,
cherry
pie)
are
linked
to
EPA­
defined
food
commodities
(
e.
g.
apples,
peeled
fruit
­
cooked;
fresh
or
N/
S;
baked;
or
wheat
flour
­
cooked;
fresh
or
N/
S,
baked)
using
publicly
available
recipe
translation
files
developed
jointly
by
USDA/
ARS
and
EPA.
For
chronic
exposure
assessment,
consumption
data
are
averaged
for
the
entire
U.
S.
population
and
within
population
subgroups,
but
for
acute
exposure
assessment
are
retained
as
individual
consumption
events.
Based
on
analysis
of
the
1994­
96,
98
CSFII
consumption
data,
which
took
into
account
dietary
patterns
and
survey
respondents,
HED
concluded
that
it
is
most
appropriate
to
report
risk
for
the
following
population
subgroups:
the
general
U.
S.
population,
all
infants
(<
1
year
old),
children
1­
2,
children
3­
5,
children
6­
12,
youth
13­
19,
adults
20­
49,
females
13­
49,
and
adults
50+
years
old.

For
chronic
dietary
exposure
assessment,
an
estimate
of
the
residue
level
in
each
food
or
foodform
(
e.
g.,
orange
or
orange
juice)
on
the
food
commodity
residue
list
is
multiplied
by
the
average
daily
consumption
estimate
for
that
food/
food
form.
The
resulting
residue
consumption
estimate
for
each
food/
food
form
is
summed
with
the
residue
consumption
estimates
for
all
other
food/
food
forms
on
the
commodity
residue
list
to
arrive
at
the
total
average
estimated
exposure.
Durations
of
chronic
exposure
vary
from
one­
year
as
represented
by
"
all
infants,"
to
lifetime
exposure
as
represented
by
the
general
U.
S.
population,
which
combines
all
population
subgroups
to
form
a
mean
exposure
value.
It
should
be
noted
that
all
parameters
of
chronic
dietary
exposure
estimates
are
averaged
values
(
i.
e.
average
food
consumption,
average
residue,
etc.).
Dietary
exposure
estimates
are
also
factored
by
the
estimated
weighted
average
usage,
or
"
percent
crop
treated"
data.

For
acute
exposure
assessments,
individual
one­
day
food
consumption
data
are
used
on
an
individual­
by­
individual
basis.
The
reported
consumption
amounts
of
each
food
item
can
be
Page
55
of
105
multiplied
by
a
residue
point
estimate
and
summed
to
obtain
a
total
daily
pesticide
exposure
for
a
deterministic
exposure
assessment,
or
"
matched"
in
multiple
random
pairings
with
residue
values
and
then
summed
in
a
probabilistic
assessment.
The
resulting
distribution
of
exposures
is
expressed
as
a
percentage
of
the
aPAD
on
both
a
user
(
i.
e.,
those
who
reported
eating
relevant
commodities/
food
forms)
and
a
per­
capita
(
i.
e.,
those
who
reported
eating
the
relevant
commodities
as
well
as
those
who
did
not)
basis.
In
accordance
with
HED
policy,
per
capita
exposure
and
risk
are
reported
for
all
tiers
of
analysis.

Estimated
Drinking
Water
Concentrations
(
EDWCs)
are
used
directly
in
dietary
exposure
assessments
to
calculate
aggregate
dietary
(
food
+
water)
risk.
This
is
done
by
using
the
relevant
model
value
as
a
residue
for
drinking
water
(
all
sources)
in
the
dietary
exposure
assessment.
The
principal
advantage
of
this
approach
is
that
the
actual
individual
body
weight
and
water
consumption
data
from
the
CSFII
are
used,
rather
than
assumed
weights
and
consumption
for
broad
age
groups.
This
refinement
has
been
used
in
estimating
the
dietary
exposure
component
in
the
triadimefon
aggregate
risk
assessment.

5.8.2
Triadimefon­
Specific
Dietary
Exposure
Data
The
triadimefon
aPAD
is
0.0034
mg/
kg
bw/
day
based
on
a
NOAEL
of
3.4
mg/
kg
bw/
day
and
an
uncertainty
factor
of
1,000,
and
applies
to
the
overall
U.
S.
population,
or
any
population
subgroup
Based
on
the
same
study,
the
triadimefon
cPAD
is
also
0.0034
mg/
kg
bw/
day,
and
risk
estimates
apply
to
the
overall
U.
S.
population,
or
any
population
sub­
group.

The
following
dietary
risk
estimates
are
based
on
the
aggregate
exposure
estimates
of
triadimefon
in
drinking
water
and
triadimefon
in
the
treated
crops
of;
apples,
grapes,
pears,
pineapple,
and
raspberries.
After
reassessment
of
the
data,
HED
has
now
concluded
that
the
supported
uses
on
apples,
grapes,
pears,
pineapples,
and
raspberries
result
in
a
40
CFR
§
180.6(
a)(
3)
situation
for
ruminant
commodities;
i.
e.,
there
is
no
expectation
of
finite
residues
in
ruminant
commodities
and
these
sources
have
been
dropped
from
risk
assessment.

Acute:
A
(
refined)
probabilistic
(
Monte­
Carlo)
acute
dietary
exposure
assessment
was
conducted
based
on
usage
and
residue
data.
Percent
crop
treated
(%
CT)
estimates
(
section
2.3,
above)
were
provided
by
the
Biological
Economic
Analysis
Division
(
BEAD).
BEAD
estimates
are
provided
to
HED
as
an
average
and
as
an
estimated
maximum.
The
estimated
maximum
%
CT
was
used
for
the
acute
dietary
risk
assessment.
The
"
anticipated"
residue
(
AR)
estimates
are
based
on
USDA
Pesticide
Data
Program
(
PDP)
data
and
field
trial
data.
Also,
because
monitoring
data
did
not
analyze
for
all
triadimefon
metabolites
of
concern,
the
ratio
of
total
toxic
residues
(
TTR)
to
triadimefon,
from
available
metabolism
studies,
were
used
to
estimate
the
total
residues
of
concern.
The
assessment
also
included
the
30­
year
annual
peak
surface
water
distribution
of
concentrations
that
was
generated
based
on
the
maximum
allowable
number
(
26)
of
applications
per
year.
Also,
for
comparison,
the
estimated
surface
water
distribution
of
concentrations
based
on
an
estimate
of
3
applications
to
turf
per
year,
(
as
reported
by
the
Page
56
of
105
registrant)
was
incorporated
into
the
acute
dietary
exposure
assessment.

Chronic:
A
(
refined)
chronic
dietary
exposure
assessment
was
conducted
based
on
usage
and
residue
data.
The
chronic
dietary
exposure
assessment
incorporated
percent
crop
treated
(%
CT)
estimates
provided
by
BEAD.
BEAD
estimates
are
provided
to
HED
as
an
average
and
as
an
estimated
maximum.
The
estimated
average
%
CT
was
used
for
the
chronic
dietary
risk
assessments.
The
AR
estimates
are
based
on
PDP
data
and
field
trial
data.
The
assessment
also
included
the
1
in
10­
year
annual
mean
surface
water
concentration
that
was
generated
using
the
maximum
allowable
number
of
applications
per
year.

5.8.3
Dietary
Risk
Estimates
(
Food
and
Drinking
Water
Sources
Combined)

Table
5.4
Food­
Only
Dietary
Risk
Estimates
Population
Subgroup
Acute
Dietary
(
99.9th
Percentile)
Chronic
Dietary
Exposure
(
mg/
kg/
day)
%
aPAD
Exposure
(
mg/
kg/
day)
%
cPAD
General
U.
S.
Population
0.002442
72
0.000015
1
All
Infants
(<
1
year
old)
0.003239
95
0.000029
1
Children
1­
2
years
old
0.008249
240
0.000063
2
Children
3­
5
years
old
0.005862
170
0.000047
1
Children
6­
12
years
old
0.003064
90
0.000025
1
Youth
13­
19
years
old
0.001581
47
0.000009
1
Adults
20­
49
years
old
0.001797
53
0.000010
1
Adults
50+
years
old
0.001831
54
0.000011
1
Females
13­
49
years
old
0.001930
57
0.000011
1
Page
57
of
105
Table
5.5
Upper­
Bound
(
26
Applications
Per
Year
to
Turf)
Dietary
Risk
Estimates
Population
Subgroup
Acute
Dietary
(
99.9th
Percentile)
Chronic
Dietary
Exposure
(
mg/
kg/
day)
%
aPAD
Exposure
(
mg/
kg/
day)
%
cPAD
General
U.
S.
Population
0.028541
840
0.003092
93
All
Infants
(<
1
year
old)
0.080231
2400
0.010137
300
Children
1­
2
years
old
0.037083
1100
0.004592
140
Children
3­
5
years
old
0.033309
980
0.004299
130
Children
6­
12
years
old
0.022809
670
0.002965
87
Youth
13­
19
years
old
0.021487
630
0.002235
66
Adults
20­
49
years
old
0.023236
680
0.002887
85
Adults
50+
years
old
0.018553
550
0.003037
89
Females
13­
49
years
old
0.022985
680
0.002875
85
In
Table
5.5
the
food­
based
exposure
is
unchanged
from
the
exposure
seen
above
in
Table
5.4.
The
water­
based
exposure
has
been
modified
to
demonstrate
what
may
be
considered
the
typical
application
to
turf
as
reported
by
the
registrant
(
3
applications).

Table
5.6
Typical
(
3
Applications
Per
Year
to
Turf)
Dietary
Risk
Estimates
Population
Subgroup
Acute
Dietary
(
99.9th
Percentile)
Chronic
Dietary
Exposure
(
mg/
kg/
day)
%
aPAD
Exposure
(
mg/
kg/
day)
%
cPAD
General
U.
S.
Population
0.007654
230
0.000542
16
All
Infants
(<
1
year
old)
0.024253
710
0.001755
52
Children
1­
2
years
old
0.012677
370
0.000845
25
Children
3­
5
years
old
0.010709
310
0.000779
23
Children
6­
12
years
old
0.006946
200
0.000529
16
Youth
13­
19
years
old
0.005649
170
0.000390
12
Adults
20­
49
years
old
0.006565
190
0.000501
15
Adults
50+
years
old
0.005836
170
0.000529
16
Females
13­
49
years
old
0.006548
190
0.000500
15
Page
58
of
105
6.0
RESIDENTIAL
EXPOSURE
ASSESSMENT
Residential
risk
assessment
considers
all
potential
pesticide
exposure,
other
than
exposure
due
to
residues
in
foods
or
in
drinking
water.
Exposure
may
occur
during
and
after
application
at
homes;
or
after
applications
at
golf
courses,
parks,
schools,
etc.
Each
route
of
exposure
(
oral,
dermal,
inhalation)
is
assessed,
where
appropriate,
and
risk
is
expressed
as
a
Margin
of
Exposure.

Triadimefon
products
are
marketed
for
homeowner
use
on
residential
lawns,
landscape
ornamentals,
trees,
fruit
trees,
and
grapes.
Triadimefon­
containing
products
are
also
marketed
for
use
by
professional
applicators
(
Pest
Control
Operators,
or
PCOs)
on
residential
turf,
on
golf
courses,
other
turf
such
as
recreational/
commercial
areas,
and
on
ornamental
plantings.
Based
on
these
uses,
triadimefon
is
assessed
for
the
residential
applicator
(
or
"
handler"),
for
children's
postapplication
oral
exposure
that
may
occur
from
turf
contact,
and
for
post­
application
dermal
contact.

6.1
Residential
Applicator
Exposure
/
Risk
Homeowners
(
or
others)
may
be
exposed
to
triadimefon
while
treating
their
lawns,
ornamentals,
or
fruit
trees.
Triadimefon
may
be
in
a
granular,
liquid,
or
wettable
powder
form,
and
applied
at
various
rates
by
low
pressure
handwand,
hose­
end
sprayer,
granular
spreaders,
and
injection.
HED
has
developed
residential
exposure
scenarios
for
triadimefon
based
on
the
use
sites,
formulations,
application
rates,
and
the
various
equipment
that
may
be
used
during
applications.

The
quantitative
exposure/
risk
assessment
developed
for
residential
handlers
is
based
on
these
scenarios:

(
1)
Liquid
Formulations:
Low
Pressure
Handwand
(
2)
Wettable
Powder
Formulations:
Low
Pressure
Handwand
(
3)
Liquid
Concentrates
with
Hose­
End
Sprayer
(
4)
Liquid
Concentrates
with
Hose­
End
Sprayer
(
5)
Liquid
Concentrates
with
Hose­
End
Sprayer
(
6)
Wettable
Powders
with
Hose­
End
Sprayer
(
7)
Wettable
Powders
with
Hose­
End
Sprayer
(
8)
Liquid
Concentrates
with
an
Tree
Injector
(
9)
Loading/
Applying
Granulars
via
Push
Type
Spreader
(
10)
Loading/
Applying
Granulars
via
Belly
Grinder
Risk
assessment
is
also
based
on
the
maximum
labeled
rate
for
each
specific
use:
Page
59
of
105
Table
6.1:
Summary
of
Maximum
Application
Rates
for
Residential
Uses
Crop
Target
Formulationa
Maximum
Application
Rate
Application
Equipment
(
Area
Treated
or
Amount
Handled
Daily)

Apples,
Pears
(
noncommercial
Foliage
WP
0.00062
lb
ai/
gal
low
pressure
handwand,
hose­
end
sprayer
Azalea
(
for
control
of
pine
twisting
rust
only)
Foliage
WP
0.005
lb
ai/
gal
Grapes
(
non­
commercial)
Foliage
WP
0.00094
lb
ai/
gal
Non­
commercial
greenhouse
ornamentals
(
flowering,
shrubs,
trees)
Foliage
WP
0.00625
lb
ai/
gal
L
0.00938
lb
ai/
gal
Ornamentals
(
flowering,
shrubs,
trees)
Foliage
L
0.0023
lb
ai/
gal
WP
0.0025
lb
ai/
gal
Ornamentals
(
shade
trees
and
woody
shrubs)
Foliage
L
0.000026
lb
ai/
inch
of
trunk
injection
Pines
Foliage
L
0.0023
lb
ai/
gal
low
pressure
handwand,
hose­
end
sprayer
Roses
Foliage
L
0.00029
lb
ai/
gal
Turf
Foliage
G
5.2
lb
ai/
acre
push­
type
spreader,
belly
grinder
L
0.033
lb
ai/
gal
low
pressure
handwand,
hose­
end
sprayer
a
WP
=
wettable
powder;
L
=
Liquid
concentrate;
G
=
granular
Residential
risk
estimates
are
also
based
on
estimates
(
and
assumptions)
regarding
the
body
weight
of
a
typical
residential
applicator
and
the
area
treated
per
application.
Note
also
that
residential
applicators
are
assumed
to
complete
all
elements
of
an
application
(
mix/
load/
apply)
without
use
of
protective
equipment
(
assessments
are
based
on
an
assumption
that
individuals
will
be
wearing
short­
sleeved
shirts
and
shorts).

Triadimefon­
specific
data
to
assess
the
above
exposure
scenarios
were
not
submitted
to
the
Agency
in
support
of
reregistration.
Instead,
exposure
estimates
for
these
scenarios
are
taken
from
the
Pesticide
Handlers
Exposure
Database
(
PHED,
Version
1.1
August
1998)
which
is
routinely
used
to
assess
handler
exposures
for
regulatory
actions
when
chemical­
specific
monitoring
data
are
not
available.
In
addition
to
PHED
data,
this
risk
assessment
relies
on
data
from
the
Outdoor
Residential
Exposure
Task
Force
(
ORETF).

Exposure
Factors
/
Other
Estimates:
For
triadimefon
risk
assessment,
the
average
body
weight
of
an
adult
applicator
was
set
at
70
kg
for
inhalation
exposure,
and
represents
both
males
and
Page
60
of
105
females
since
the
effects
identified
in
the
selected
toxicity
studies
were
not
sex
specific.
For
the
assessment
of
dermal
exposure,
the
average
adult
body
weight
was
set
at
60
kg
to
account
for
the
lower
body
weight
of
female
workers.
Pending
further
discussion,
the
estimate
of
60
kg
may
be
revised
to
70
kg
if
risk
estimate
refinements
are
required.
Other
factors
used
for
the
triadimefon
assessment
are
taken
from
the
HED
Science
Advisory
Committee
Policy
12:
Recommended
Revisions
To
The
Standard
Operating
Procedures
For
Residential
Exposure
Assessment
(
2/
22/
01)
and
include
the
amount/
area
treated
estimates
of:
1)
5
gallons
of
liquid
formulation
per
day
when
using
a
low­
pressure
handwand
sprayer;
2)
1,000
ft2
for
ornamental
treatments,
using
liquid
formulations
with
a
hose­
end
sprayer;
and
3)
0.5
acres
for
lawn
and
ornamental
treatments,
using
granular
formulations
with
a
bellygrinder
spreader
or
push­
type
spreader.

The
seasonal
duration
of
triadimefon
exposure
to
homeowner
applicators
is
thought
to
be
a
day,
or
a
few
days,
but
well
within
the
30
day
duration
defined
as
short­
term
for
the
purposes
of
risk
assessment.
MOE
estimates
for
applicator
exposure
scenarios
are
presented
in
Table
6.2
below.
Page
61
of
105
Table
6.2
Triadimefon
Residential
Handler
Risk
Estimates
Exposure
Scenario
Crop
or
Target
App
Ratea
(
lb
ai/
gallon)
Area
Treated
Dailyb
(
gallons)
Baseline
Unit
Exposure
MOEs
Dermalc
(
mg/
lb
ai)
Inhalationd
(
µ
g/
lb
ai)
Baseline
Dermal
Baseline
Inhalation
Baseline
Dermal
+

Baseline
Inhalation
MOE
Mixer/
Loader/
Applicator
Mixing/
Loading/

Applying
Liquid
Concentrates
with
Low
Pressure
Handwand
(
ORETF­­
fruit
trees
and
ornamentals)

(
1)
greenhouse
ornamentals
(
flowering,

shrubs,
trees)
0.00938
5
56
2.6
6900
2000000
6800
roses
0.00029
5
56
2.6
220000
63000000
220000
turf
(
home
lawns)
0.033
5
56
2.6
1900
550000
1900
ornamentals
(
flowering,

shrubs,
trees)
0.0023
5
56
2.6
28000
8000000
28000
Mixing/
Loading/

Applying
Wettable
Powders
with
Low
Pressure
Handwand
(
PHED)
(
2)
apples,
pears
0.00062
5
250
1063
23000
72000
18000
azaleas
0.005
5
250
1063
2900
9000
2200
grapes
0.00094
5
250
1063
15000
48000
12000
greenhouse
ornamentals
(
flowering,

shrubs,
trees)
0.00625
5
250
1063
2300
7200
1700
Table
6.2
Triadimefon
Residential
Handler
Risk
Estimates
Exposure
Scenario
Crop
or
Target
App
Ratea
(
lb
ai/
gallon)
Area
Treated
Dailyb
(
gallons)
Baseline
Unit
Exposure
MOEs
Dermalc
(
mg/
lb
ai)
Inhalationd
(
µ
g/
lb
ai)
Baseline
Dermal
Baseline
Inhalation
Baseline
Dermal
+

Baseline
Inhalation
MOE
Page
62
of
105
Mixing/
Loading/

Applying
Wettable
Powders
with
Low
Pressure
Handwand
(
PHED)
(
2)
(
cont.)
ornamentals
(
flowering,

shrubs,
trees)
0.0025
5
250
1063
5800
18000
4400
Mixing/
Loading/

Applying
Liquid
Concentrates
with
Hose­
End
Sprayer
(
Residential
ORETF
data
­­
fruit
trees
and
ornamental
shrubs)

(
3)
ornamentals
(
shrubs,
trees)
0.0023
100
39
1.6
2000
650000
2000
pines
0.0023
100
39
1.6
2000
650000
2000
roses
0.00029
100
39
1.6
16000
5100000
16000
Mixing/
Loading/

Applying
Liquid
Concentrates
with
Hose­
End
Sprayer
(
Residential
ORETF
data 

gardens)
(
4)
ornamentals
(
flowering)
0.0023
100
34
0.82
2300
1300000
2300
Table
6.2
Triadimefon
Residential
Handler
Risk
Estimates
Exposure
Scenario
Crop
or
Target
App
Ratea
(
lb
ai/
gallon)
Area
Treated
Dailyb
(
gallons)
Baseline
Unit
Exposure
MOEs
Dermalc
(
mg/
lb
ai)
Inhalationd
(
µ
g/
lb
ai)
Baseline
Dermal
Baseline
Inhalation
Baseline
Dermal
+

Baseline
Inhalation
MOE
Page
63
of
105
Mixing/
Loading/

Applying
Liquid
Concentrates
with
Hose­
End
Sprayer
(
Residential
ORETF
data 
turf)

(
5)
turf
(
home
lawns)
0.033
100
11
17
500
4200
440
Mixing/
Loading/

Applying
Wettable
Powders
with
Hose­

End
Sprayer
(
Residential
ORETF
data
­­

liquid
concentrate
application
to
fruit
trees
and
ornamentals)
(
6)
apples,
pears
0.00062
100
39
1.6
7400
2400000
7400
grapes
0.00094
100
39
1.6
4900
1600000
4900
ornamentals
(
shrubs,
trees)
0.0025
100
39
1.6
1800
600000
1800
Table
6.2
Triadimefon
Residential
Handler
Risk
Estimates
Exposure
Scenario
Crop
or
Target
App
Ratea
(
lb
ai/
gallon)
Area
Treated
Dailyb
(
gallons)
Baseline
Unit
Exposure
MOEs
Dermalc
(
mg/
lb
ai)
Inhalationd
(
µ
g/
lb
ai)
Baseline
Dermal
Baseline
Inhalation
Baseline
Dermal
+

Baseline
Inhalation
MOE
Page
64
of
105
Mixing/
Loading/

Applying
Wettable
Powders
with
Hose­

End
Sprayer
(
Residential
ORETF
data
­

liquid
concentrates
application
to
gardens)
(
7)
azaleas
0.005
100
34
0.82
1100
580000
1100
ornamentals
(
flowering)
0.0025
100
34
0.82
2100
1200000
2100
Mixing/
Loading/

Applying
Liquid
Concentrates
with
an
Tree
Injector
(
8)
Ornamentals
(
shade
trees,

woody
shrubs)
0.000026lb
ai/
inch
of
trunk
inches
of
trunk
No
Data
No
Data
No
Data
No
Data
No
Data
Loading/
Applying
Granulars
via
Push
Type
Spreader
(
ORETF
data)
(
9)
turf
5.2
lb
ai/
acre
0.5
acres
0.67
0.88
10000
100000
9400
Loading/
Applying
Granulars
via
Belly
Grinder
(
PHED
data)
(
10)
turf
0.00012
lb
ai/
ft2
1000
ft2
110
62
1400
32000
1300
a
Application
rates
are
the
maximum
application
rates
determined
from
EPA
registered
labels
for
triadimefon
b
Amount
handled
per
day
values
are
HED
estimates
of
acres,
square
feet,
or
cubic
feet
treated
or
gallons
applied
based
on
Exposure
SAC
SOP
#
9,
and
HED
estimates.

c
Baseline
Dermal:
Long­
sleeve
shirt,
long
pants,
no
gloves.

d
Baseline
Inhalation:
no
respirator.
Page
65
of
105
6.2
Residential
Handler
Risk
Summary
Generally,
the
risk
estimates
associated
with
most
triadimefon
exposure
scenarios
greater
than
the
target
MOE
level
of
1,000.
All
inhalation
risk
estimates
are
above
the
MOE
level
of
1,000.
Only
one
dermal
exposure
scenario,
mixing/
loading/
applying
liquid
concentrates
with
a
hose­
end
sprayer
(
ORETF
data)
to
home
lawns
(
MOE
estimate
of
500),
was
found
to
be
below
HED's
level
of
concern.
The
significant
data
gap
identified
by
HED
for
residential
handlers
is
mixing/
loading/
applying
liquids
with
a
tree
injector.
HED
has
no
data
for
this
scenario
and
is
not
aware
of
any
surrogate
data
that
could
be
applied
to
this
scenario.

6.2
Residential
Postapplication
Exposure
/
Risk
Exposure
to
triadimefon
occurs
in
the
residential
environment
following
applications
by
professionals,
or
homeowners,
to
lawns,
ornamentals,
and
fruit
trees.
Exposure
to
triadimefon
also
occurs
following
applications
by
professionals
to
private
or
public
areas
such
as
golf
courses,
parkland,
etc.
The
following
exposure
scenarios,
and
population
groups,
are
assessed
for
triadimefon:
1)
incidental
ingestion
(
oral)
exposure
of
children
from
ingesting
or
mouthing
treated
turf,
or
from
treated
soil
(
i.
e.,
soil
ingestion,
granule
ingestion,
and
hand­/
object­
tomouth
2)
dermal
exposure
of
adults
based
on
activities
on
lawns,
gardens,
golf
courses,
and
parks
previously
treated
with
triadimefon;
and
3)
dermal
exposure
of
children
(
aged
10
to
12)
based
on
activities
on
their
lawns,
gardens,
golf
courses,
and
parks
previously
treated
with
triadimefon.
Each
of
these
assessments
were
chosen
to
establish
the
upper­
end
of
possible
exposure
for
each
of
the
3
representative
age
groups.
A
Margin
of
Exposure
of
1,000
(
or
more)
is
considered
adequately
protective
for
these
assessments.

Exposure
Scenarios:
The
quantitative
exposure/
risk
assessment
developed
for
postapplication
exposure
is
based
on
these
scenarios:

Dermal
exposure
from
treated
turf:
postapplication
exposure
to
children,
youth,
and
adults
from
contact
with
treated
turf.

Dermal
exposure
from
treated
gardens:
postapplication
exposure
to
youth
and
adults
from
contact
with
treated
gardens.

Hand­
to­
mouth
activity
from
treated
turf:
Postapplication
dose
among
children
from
the
"
incidental"
ingestion
of
pesticide
residues
on
treated
turf
from
hand­
to­
mouth
transfer
(
i.
e.,
those
residues
that
end
up
in
the
mouth
from
a
child
touching
turf
and
then
putting
their
hands
in
their
mouth).

Object­
to­
mouth
activity
from
treated
turf:
Postapplication
dose
among
children
from
incidental
ingestion
of
pesticide
residues
on
treated
turf
from
object­
to­
mouth
transfer
(
i.
e.,
those
residues
that
end
up
in
the
mouth
from
a
child
mouthing
a
handful
of
treated
turf);
Page
66
of
105
Dose
from
soil
ingestion
activity:
Postapplication
dose
among
children
from
incidental
ingestion
of
soil
in
a
treated
area;

Dose
from
ingestion
of
triadimefon
granules
from
treated
turf:
Postapplication
dose
among
children
from
the
"
episodic"
ingestion
of
pesticide
granules
picked
up
from
treated
turf.
The
term
"
episodic"
is
used
to
denote
an
event
(
granule
ingestion)
that
is
infrequent
to
very
infrequent.
The
term
"
incidental"
is
used
to
denote
the
more
likely
oral
ingestion
that
may
occur
following
typical
lawn
treatments.
Both
terms
are
used
to
distinguish
the
seasonal
and
inadvertent
oral
exposure
associated
with
lawn
use.
The
exposure
estimates
of
the
oral
ingestion
scenarios
(
except
granule
ingestion)
are
combined
to
establish
the
possible
(
if
not
likely)
upper­
end
of
oral
exposure
from
lawn
(
or
similar)
use.

Dose
from
dermal
exposure
while
golfing:
Postapplication
dermal
dose
calculations
for
adults
and
youth­
aged
children
(
ages
10
to
12)
while
golfing.

Exposure
Factors
/
Other
Estimates:

°
Five
percent
of
the
turf
application
rate
has
been
used
to
calculate
the
day­
zero
residue
levels
used
for
assessing
risks
from
dermal
and
hand­
to­
mouth
exposures.
°
Twenty
percent
of
the
turf
application
rate
has
been
used
to
calculate
the
day­
zero
residue
levels
used
for
assessing
risks
from
object­
to­
mouth
behaviors.
°
Toddlers
are
expected
to
weigh
15
kilograms
(
representing
an
average
weight
from
years
one
to
six).
°
Hand­
to­
mouth
exposures
are
based
on
a
frequency
of
20
events/
hour
and
a
surface
area
per
event
of
20
cm2.
°
Object­
to­
mouth
exposures
are
based
on
a
25
cm2
surface
area.
°
Exposure
durations
for
turfgrass
scenarios
are
estimated
to
be
2
hours.
°
Soil
residues
are
contained
in
the
top
centimeter
and
soil
density
is
0.67
mL/
gram.
°
A
12
year
old
youth
is
expected
to
weigh
39.1
kilograms.
°
For
gardening
scenarios,
20
percent
of
the
application
rate
is
available
for
transfer,
since
no
triadimefon­
specific
DFR
data
are
available.
Page
67
of
105
Table
6.1
Adult
/
Postapplication
Risk
Estimates
Exposure
Scenario
Route
of
Exposure
Formulation
Application
Rate
(
lb
ai/
acre)
MOE
at
Day
0
Residential
Turf
(
High
Contact
Activities)
Dermal
Spray
5.4
210
Granular
5.2
210
Residential
Turf
(
Mowing)
Dermal
Spray
5.4
870
Granular
5.2
910
Home
Garden
(
Ornamentals)
Dermal
Spray
5.4
220
Granular
5.2
230
Golfer
Dermal
Granular
5.2
12000
Table
6.2
Youth
/
Postapplication
Risk
Estimates
Exposure
Scenario
Route
of
Exposure
Formulation
Application
Rate
(
lb
ai/
acre)
MOE
/
Day
0
Residential
Turf
(
Mowing)
Dermal
Spray
5.4
570
Granular
5.2
590
Home
Garden
(
Ornamentals)
Dermal
Spray
5.4
590
Granular
5.2
610
Golfer
Dermal
Granular
5.2
7700
Table
6.3
Children
/
Postapplication
Risk
Estimates
Exposure
Scenario
Route
of
Exposure
Formulation
Application
Rate
(
lb
ai/
A)
MOE
/
Day
0
Residential
Turf
(
High
Contact
Activities)
Dermal
Spray
5.4
140
Granular
5.2
150
Hand
to
Mouth
Activity
on
Turf
Oral
Spray
5.4
42
Granular
5.2
44
Object
to
Mouth
Activity
on
Turf
Oral
Spray
5.4
170
Granular
5.2
170
Incidental
Soil
Ingestion
Oral
Spray
5.4
13000
Granular
5.2
13000
Incidential
Ingestion
of
Granules
or
Pellets
Oral
Granular
5.2
(
1%
ai
in
formulation)
50
Page
68
of
105
Page
69
of
105
Table
6.4:
Triadimefon
Residential
Scenarios
for
Combined
Risk
Estimates
Postapplication
Exposure
Scenario
Margins
of
Exposure
(
MOEs)
(
UF=
100)

Short­
Term
Oral
(
Non­
Dietary)
Total
Non­
Dietary
Risk
Turf
Toddler
Turf
­
sprays
(
5.4
lb
ai/
acre)
Hand
to
Mouth
42
27
Object
to
Mouth
170
Incidental
Soil
Ingestion
13000
Dermal
140
Toddler
Turf
­
granulars
(
5.2
lb
ai/
acre)
Hand
to
Mouth
44
28
Object
to
Mouth
170
Incidental
Soil
Ingestion
13000
Dermal
150
The
"
Total
Non­
Dietary
Risk"
estimates
presented
in
Table
6.4,
above,
are
considered
upper­
end
estimates
suitable
as
risk
screening
tools.
This
assessment
could
be
refined
with
triadimefonspecific
turt
transferable
residue
(
TTR)
data.

7.0
AGGREGATE
RISK
ASSESSMENT
As
part
of
the
reregistration
eligibility
decision,
the
Agency
is
required
by
the
Food
Quality
Protection
Act
to
ensure
"
that
there
is
reasonable
certainty
that
no
harm
will
result
from
aggregate
exposure
to
pesticide
chemical
residue,
including
all
anticipated
dietary
exposures
and
other
exposures
for
which
there
is
reliable
information."

7.1
Spray
Drift
The
Agency
recognizes
that
exposure
due
to
spray
drift
may
also
contribute
to
the
aggregate
exposure
of
individuals
that
work
or
live
near
agricultural
sites.
At
this
time,
exposure
to
triadimefon
from
this
source
cannot
be
quantified.
The
following
statement
summarizes
the
Agency's
current
position
on
this
issue.

Spray
drift
is
always
a
potential
source
of
exposure
to
residents
adjacent
to
spraying
operations.
This
is
particularly
the
case
with
aerial
application,
but,
to
a
lesser
extent,
could
also
be
a
potential
source
of
exposure
from
groundboom
application
methods.
The
Agency
has
been
working
with
the
Spray
Drift
Task
Force,
EPA
Regional
Offices
and
State
Lead
Agencies
for
pesticide
regulation
and
other
parties
to
develop
the
best
spray
drift
management
practices.
The
Agency
is
now
requiring
interim
mitigation
measures
for
aerial
applications
that
must
be
placed
on
product
labels/
labeling.
The
Agency
has
completed
its
evaluation
of
the
new
data
base
submitted
by
the
Spray
Drift
Task
Force,
Page
70
of
105
a
membership
of
U.
S.
pesticide
registrants,
and
is
developing
a
policy
on
how
to
appropriately
apply
the
data
and
the
AgDRIFT
computer
model
to
its
risk
assessments
for
pesticides
applied
by
air,
orchard
airblast
and
ground
hydraulic
methods.
After
the
policy
is
in
place,
the
Agency
may
impose
further
refinements
in
spray
drift
management
practices
to
reduce
off­
target
drift
and
risks
associated
with
aerial
as
well
as
other
application
types
where
appropriate.

7.2
Aggregate
(
Food
/
Water
/
Residential)
Risk
Estimates
The
exposure
attributable
to
residential
uses
of
triadimefon
have
not
been
aggregated
with
dietary
sources
of
exposure
(
food
plus
drinking
water)
at
this
time
as
the
dietary
and
residential
exposure
pathways
separately
exceed
HED's
level
of
concern.
The
Agency
is
soliciting
comments
on
assumptions
used
in
the
current
risk
assessment.
In
the
event
that
refinements
can
be
made
in
the
future,
multiple
routes
and
sources
of
exposure
may
be
aggregated.
It
should
be
noted
that
the
use
of
triadimefon
also
results
in
potential
exposures
and
risk
to
its
metabolite,
triadimenol,
also
a
pesticidal
active
ingredient.
Triadimenol
is
currently
being
evaluated
by
the
Agency
and
a
Tolerance
Reassessment
Eligibility
Decision
(
TRED)
document
will
address
exposure
to
this
metabolite.

The
decision
not
to
aggregate
was
based
on
the
risks
associated
with
the
use
of
triadimefon,
as
the
risk
from
triadimefon
already
exceed
the
Agency's
level
of
concern
by
itself.
Furthermore,
the
Agency
feels
that
aggregating
the
metabolite
triadimenol
exposures
from
use
of
triadimefon
with
the
exposures
resulting
from
the
use
of
triadimenol
would
not
allow
for
the
proper
evaluation
of
the
use
of
triadimenol
active
ingredient
products.
Should
refinements
be
possible
in
the
future,
it
may
be
possible
and
appropriate
to
aggregate
multiple
routes
and
sources
of
exposures
for
these
chemicals.

8.0
CUMULATIVE
RISK
ASSESSMENT
Unlike
other
pesticides
for
which
EPA
has
followed
a
cumulative
risk
approach
based
on
a
common
mechanism
of
toxicity,
EPA
has
not
made
a
common
mechanism
of
toxicity
finding
as
to
triadimefon
and
any
other
substances.
For
the
purposes
of
this
action,
therefore,
EPA
has
not
assumed
that
triadimefon
has
a
common
mechanism
of
toxicity
with
other
substances.
For
information
regarding
EPA's
efforts
to
determine
which
chemicals
have
a
common
mechanism
of
toxicity
and
to
evaluate
the
cumulative
effects
of
such
chemicals,
see
the
policy
statements
released
by
EPA's
Office
of
Pesticide
Programs
concerning
common
mechanism
determinations
and
procedures
for
cumulating
effects
from
substances
found
to
have
a
common
mechanism
on
EPA's
website
at
http://
www.
epa.
gov/
pesticides/
cumulative/.
Page
71
of
105
9.0
OCCUPATIONAL
EXPOSURE
/
RISK
Occupational
risk
is
assessed
for
exposure
at
the
time
of
application
(
termed
"
handler"
exposure)
and
assessed
for
exposure
following
application,
or
post­
application
exposure.
Application
parameters
are
generally
defined
by
the
physical
nature
of
the
formulation
(
e.
g.,
formula
and
packaging),
by
the
equipment
required
to
deliver
the
chemical
to
the
use
site,
and
by
the
application
rate
required
to
achieve
an
efficacious
dose.
Post­
application
risk
is
assessed
for
activites
such
as
scouting,
irrigating,
pruning,
and
harvesting
and
is
based
primarily
on
dermal
exposure
estimates.
Note
that
occupational
risk
estimates
are
intended
to
represent
professional
pesticide
workers,
and
on
this
basis
assumptions
are
made
concerning
acres
treated
per
day
and
the
seasonal
duration
of
exposure.

Occupational
risk
estimates
are
expressed
as
Margins
of
Exposure,
or
MOEs,
which
are
the
ratio
of
estimated
exposure
to
an
established
dose
level
(
NOAEL/
LOAEL).
Triadimefon
MOEs
are
determined
by
a
comparison
of
specific
exposure
scenario
estimates
to
the
dose
level
(
NOAEL)
of
300
mg/
kg/
day
for
short­
and
intermediate­
term
dermal
assessment,
and
3.4
mg/
kg/
day
for
shortand
intermediate­
term
inhalation
assessment.
For
triadimefon
users
the
Agency
has
established
a
"
target"
MOE
of
100
(
for
both
short­
and
intermediate­
term
exposure)
based
on
the
standard
uncertainty
factors
of
10x
for
interspecies
extrapolation,
and
10x
for
intraspecies
variability.
Long­
term
worker
exposure
is
not
expected
or
assessed
for
triadimefon.

9.1
Occupational
Handler
Overview
The
Agency
uses
the
term
"
handlers"
to
describe
those
individuals
who
are
involved
in
the
pesticide
application
process.
For
occupational
risk
assessment
,
the
Agency
identifies
the
distinct
job
functions,
or
tasks,
related
to
application
methods
and
estimates
exposures
depending
on
the
specifics
of
each
task.
Job
requirements
such
as
amount
of
chemical
to
be
used
in
an
application,
the
kinds
of
equipment
used,
the
target
of
treatment,
and
the
circumstances
of
the
user
(
e.
g.,
the
level
of
protection
used
by
an
applicator)
can
cause
exposure
levels
to
differ
in
a
manner
specific
to
each
application
event.
The
Agency
completes
risk
assessments
using
maximum
application
rates
for
each
scenario
for
screening
purposes.

Occupational
handler
exposure
assessments
are
completed
by
the
Agency
using
different
levels
of
personal
protection.
The
Agency
typically
evaluates
all
exposures
with
a
tiered
approach.
The
lowest
tier
is
represented
by
the
baseline
exposure
scenario
(
i.
e.,
long­
sleeve
shirt,
long
pants,
shoes,
and
socks)
followed
by
increasing
the
levels
of
personal
protective
equipment
or
PPE
(
e.
g.,
gloves,
double­
layer
body
protection,
and
respirators)
and
engineering
controls
(
e.
g.,
closed
cabs
and
closed
mixing/
loading
systems).
This
approach
is
used
by
the
Agency
in
order
to
define
label
language
using
a
risk­
based
approach.
In
addition,
the
minimal
level
of
adequate
protection
for
a
chemical
is
generally
considered
by
the
Agency
to
be
the
most
practical
option
for
risk
reduction
because
over­
burdensome
risk
mitigation
measures
are
not
considered
a
practical
alternative.

9.2
Triadimefon­
Specific
Application
Descriptions
Page
72
of
105
Occupational
Mixers
and/
or
Loaders:
Workers
that
perform
tasks
in
preparation
for
an
application
(
but
do
not
apply).
For
example,
prior
to
application,
they
would
prepare
dilute
spray
solutions
and
load
those
dilute
spray
solutions
into
application
equipment
such
as
a
groundboom
tractor
or
they
would
load/
transfer
solid
materials
(
granulars)
into
tractor­
drawn
spreader
equipment.

Occupational
Applicators:
Workers
that
operate
application
equipment
such
as
groundboom
sprayers
for
liquids
or
tractor­
drawn
spreaders
for
granular
materials
(
but
do
not
mix
or
load).

Occupational
Mixer/
Loader/
Applicators:
Workers
that
are
involved
in
the
entire
pesticide
application
process
(
i.
e.,
they
do
all
job
functions
related
to
a
pesticide
application)
.
These
individuals
prepare
dilute
spray
solutions
and
also
apply
the
solution.
The
Agency
considers
some
exposures
to
be
mixer/
loader/
applicator
exposures
because
of
the
equipment
used
and
the
logistics
associated
with
such
applications.
For
example,
if
one
uses
a
small
handheld
device,
such
as
a
low­
pressure
handwand
sprayer,
it
is
anticipated
that
one
individual
will
mix
the
spray
solution
and
then
apply
it,
because
of
labor
and
logistical
considerations.

Flaggers:
Workers
that
guide
aerial
applicators
during
the
release
of
a
pesticide
product
onto
an
intended
target.

Commercial
Nursery
Seed
Treatment
Loader/
Applicator:
The
possible
points
of
operator
exposure
for
nursery
treatment
are:
transport
of
pesticide
in
mobile
containers,
moving
pesticide
from
storage
into
seed
treatment
equipment,
introduction
of
pesticide
into
seed
treatment
equipment,
and
equipment
cleaning
and
maintenance.
Nursery
seed
treatment
with
liquid
formulations
is
generally
done
with
more
automated
equipment,
essentially
miniature
versions
of
commercial
treaters.
Seed
may
be
treated
as
it
is
augured
from
the
grower's
truck
to
the
storage
bin
(
at
the
farmstead),
or
from
the
truck
to
the
seeder
(
field),
or
from
the
grower's
storage
bin
into
either
a
truck
or
seeder.

Commercial
Nursery,
Planting
of
Treated
Seed:
Planting
exposures
occur
during
both
the
loading
of
hoppers
and
driving
the
equipment.

Commercial
Mixer/
Loader/
Applicator
for
Seed
Treatments:
This
scenario
involves
loading/
applying
of
all
formulations
in
a
commercial
operation.

Commercial
Bagger
for
Seed
Treatments:
Seed
is
bagged
by
a
machine
which
picks
up
a
bag,
opens
it,
slips
it
over
a
spout
and
lets
it
fill
to
a
predetermined
weight.
The
bagger
then
folds
the
top
of
the
bag,
attaches
the
seed
grade
certificates
and
treatment
tags.

Commercial
Sewer
for
Seed
Treatments:
After
bagging
the
treated
seed
the
sewer
shuts
the
bag
using
an
automatic
sewing
machine.
The
bag
is
then
moved
by
a
conveyer
belt
to
a
pallet
area
where
it
is
stacked
for
shipping.
Page
73
of
105
Multiple
Commercial
Activities
for
Seed
Treatments:
The
SOP
contains
a
scenario
labeled
"
Multiple
Activities"
to
address
the
potential
for
multiple
types
of
exposure
in
small
commercial
operations.

9.3
Exposure
Duration
It
is
likely
that
triadimefon
exposures
will
occur
in
a
variety
of
patterns.
Occupational
triadimefon
exposures
can
occur
for
a
single
day,
or
up
to
weeks
at
a
time
for
custom
(
commercial)
applicators
who
are
completing
a
number
of
applications
for
a
number
of
different
clients.
Intermittent
exposures
over
several
weeks
are
also
anticipated
for
some
workers.
Therefore,
short­
and
intermediate­
term
exposure
was
assessed.

9.4
Exposure
Scenario
Summary
HED
identified
occupational
exposure
scenarios
based
on
the
use
sites,
formulations,
and
the
various
equipment
that
may
be
used
for
triadimefon
applications.

Mixer/
Loaders:

(
1a)
Liquid
Formulations
for
Aerial
Applications
(
1b)
Liquid
Formulations
for
Groundboom
Applications
(
1c)
Liquid
Formulations
for
Airblast
Applications
(
2a)
Wettable
Powders
for
Aerial
Applications
(
2b)
Wettable
Powders
for
Chemigation
Applications
(
2c)
Wettable
Powders
for
Groundboom
Applications
(
2d)
Wettable
Powders
to
support
LCO
Handgun
Applications
(
2e)
Wettable
Powders
for
Airblast
Applications
(
2f)
Wettable
Powders
to
support
Rights­
of­
Way
Applications
(
3a)
Water
Dispersible
Granules
for
Aerial
Applications
(
3b)
Water
Dispersible
Granules
for
Chemigation
Applications
(
3c)
Water
Dispersible
Granules
for
Groundboom
Applications
(
3d)
Water
Dispersible
Granules
to
support
LCO
Handgun
Applications
(
4a)
Loading
Granulars
for
Aerial
Applications
(
4b)
Loading
Granulars
for
Tractor
Drawn
Spreader
Applications
Applicators:

(
5)
Aerial
Spray
Applications
(
6)
Aerial
Granular
Applications
(
7)
Groundboom
Spray
Applications
(
8)
Airblast
Spray
Applications
(
9)
Handgun
Spray
Applications
(
10)
Rights
of
Way
Spray
Applications
Page
74
of
105
(
11)
Tractor­
Drawn
Spreader
Granule
Applications
Flaggers:

(
12)
Flagging
for
Aerial
Spray
Applications
(
13)
Flagging
for
Aerial
Granular
Applications
Mixer/
Loader/
Applicators:

(
14)
Liquid
Formulations:
Low
Pressure
Handwand
Sprayer
(
ORETF)
(
15)
Wettable
Powder
Formulations:
Low
Pressure
Handwand
Sprayer
(
PHED)
(
16)
Water
Dispersible
Granules
with
Low
Pressure
Handwand
(
17)
Liquid
Formulations:
Handgun
Sprayer
(
ORETF)
(
18)
Wettable
Powders
with
a
Handgun
Sprayer
(
ORETF
data)
(
19)
Water
Soluble
Bags
with
Handgun
Sprayer
(
ORETF
data)
(
20)
Dry
Flowables
Concentrates
with
a
Handgun
Sprayer
(
ORETF
data)
(
21)
Liquid
Formulations:
High
Pressure
Sprayer
(
PHED)
(
22)
Water
Dispersible
Granules:
High
Pressure
Handwand
(
PHED:
liquid
concentrates)
(
23)
Wettable
Powders:
High
Pressure
Handwand
(
PHED:
liquid
concentrates)
(
24)
Liquids
with
an
Tree
Injector
(
25)
RTU:
Briquette
(
26)
Liquid
Formulations:
Dip
(
27)
Loading/
Applying
Granulars
via
Push
Type
Spreader
(
ORETF)

Pine
seed
treatment:

(
1)
loading
and
applying
wettable
powder
formulations
with
commercial
seed­
treatment
equipment,
(
2)
commercial
sewer
stitching
bags
of
seed,
(
3)
bagging
and
otherwise
handling
treated
seeds
with
commercial
equipment,
(
4)
multiple
commercial
seed
treatment
activities,
(
5)
on­
nursery
loading/
applying
with
hopper
or
planter
box
seed
treatment,
and
(
6)
on­
nursery
loading/
planting
previously
treated
seeds.

9.5
Application
Rates
Page
75
of
105
Table
9.1
Summary
of
Maximum
Application
Rates
for
Commercial
and
Agricultural
Uses
Crop
Target
Formulationa
Maximum
Application
Rate
Application
Equipment
(
Area
Treated
or
Amount
Handled
Daily)

Apples,
Pears
(
noncommercial
Foliage
WSP,
WP
0.25
lb
ai/
acre
or
0.00062
lb
ai/
gal
aerial,
airblast
low
pressure
handwand,
handgun
(
WP
only)

Azaleas
(
for
control
of
pine
twisting
rust
only)
Foliage
WDG,
WP,
WSP
0.005
lb
ai/
gal
chemigation,
groundboom,
low
pressure
handwand,
high
pressure
handwand
Christmas
trees
Foliage
WP
0.25
lb
ai/
acre
aerial,
airblast
Grapes
Foliage
L
0.125
lb
ai/
acre
airblast,
aerial,
groundboom,
low
pressure
handwand
WP
0.00094
lb
ai/
gal
low
pressure
handwand,
handgun
Grapes
Foliage
WP,
WSP
0.188
lb
ai/
acre
aerial,
airblast,
groundboom
Non­
commercial
greenhouse
ornamentals
(
flowering,
shrubs,
trees)
WP
0.00625
lb
ai/
gal
low
pressure
handwand
WSP
0.00625
lb
ai/
gal
low
pressure
handwand,
high
pressure
handwand,
handgun
L
0.00938
lb
ai/
gal
Ornamentals
(
flowering,
shrubs,
trees)
Foliage
L
0.0023
lb
ai/
gal
low
pressure
handwand,
high
pressure
handwand,
handgun
WDG,
WP
0.0025
lb
ai/
gal
chemigation,
groundboom,
low
pressure
handwand,
high
pressure
handwand
Ornamentals
(
shade
trees
and
wood
shrubs)
Trunk
L
0.000075
lb
ai/
inch
of
trunk
RTU
micro­
injection
unit
0.000026
lb
ai/
inch
of
trunk
Injection
Pine
(
including
Christmas
trees)
Foliage
L
0.0023
lb
ai/
gal
handgun,
low
pressure
handwand
Pine
(
seedlings)
Soil
(
preplant
RTU
­
Briquette
0.00019
lb
ai/
seedling
(
1
briquette
per
seedling)
mechanical
equipment
Table
9.1
Summary
of
Maximum
Application
Rates
for
Commercial
and
Agricultural
Uses
Crop
Target
Formulationa
Maximum
Application
Rate
Application
Equipment
(
Area
Treated
or
Amount
Handled
Daily)

Page
76
of
105
Foliage
WP,
WSP
0.5
lb
ai/
acre
aerial,
airblast,
groundboom,
handgun,
low
pressure
handwand
Pine
Seed
(
nurseries)
Seeds
WP
0.0000625
lb
ai/
gal
soak/
dip
treatment
0.13
lb
ai/
100
lb
seeds
commercial
treater
Pineapple
(
post­
harvest
or
per­
plant
crown)
Fruit
or
Crown
WP
0.0028
lb
ai/
gal
dip
or
spray
Raspberries
(
only
in
CA)
Foliage
WP,
WSP
0.125
lb
ai/
acre
airblast,
groundboom
Roses
Foliage
L
0.00029
lb
ai/
gal
handgun,
low
pressure
handwand,
high
pressure
handwand
Turf
Foliage
G
2.6
lb
ai/
acre
aerial,
tractor­
drawn
spreader
L
0.64
lb
ai/
acre
groundboom,
low
pressure
handwand
Turf
Foliage
WDG
2.7
lb
ai/
acre
aerial,
chemigation,
groundboom,
low
pressure
handwand,
handgun,
rights­
of­
way
sprayer
(
WP
and
WSP
only)

WP,
WSP
5.4
lb
ai/
acre
aerial,
chemigation,
groundboom,
low
pressure
handwand,
handgun,
rights­
of­
way
sprayer
(
WP
and
WSP
only)

Turf
(
golf
course)
G
1.36
lb
ai/
acre
tractor­
drawn
spreader,
push­
type
spreader
a
WSP
=
water
soluble
packet;
WP
=
wettable
powder;
L
=
Liquid
concentrate;
G
=
granular;
WDG
=
water
dispersible
granule;
RTU
=
ready­
to­
use
liquid
9.6
Occupational
Handler
Risk
Estimates
The
following
tables
summarize
the
estimated
exposure
and
risk
(
MOE
approach)
for
all
handler
Page
77
of
105
exposure
scenarios.
Page
78
of
105
Table
9.2
Combined
Dermal
/
Inhalation
Exposure
Scenario
Crop
or
Target
App
Rate
(
lb
ai/
acre)
a
Area
Treated
Daily
(
acre)
b
Combined
MOEsj
Baselinec
Dermal
+

Baseline
Inh
Single
layer
w/
glovesd
Dermal
+

Baseline
Inh
Double
layer
w/

glovese
Dermal
+

Baseline
Inh
Single
layer
w/
gloves
Dermal
+

80%
Rf
Inh
Single
layer
w/
gloves
Dermal
+

90%
Rg
Inh
Double
layer
w/

gloves
Dermal
+

80%
R
Inh
Double
layer
w/

gloves
Dermal
+

90%
R
Inh
Eng
Controli
Dermal
+

Inh
Mixer/
Loader
Mixing/

Loading
Liquid
Concentrates
for
Aerial
Applications
(
1a)
grapes
0.125
350
140
3600
3800
10000
13000
12000
16000
28000
Mixing/

Loading
Liquids
Concentrates
for
Groundboom
Applications
(
1b)
grapes
0.125
80
600
16000
17000
44000
56000
51000
69000
120000
turf
(
sod
farm)
0.64
80
120
3100
3300
8500
11000
10000
13000
24000
turf
(
golf
course)
0.64
80
120
3100
3300
8500
11000
10000
13000
24000
Mixing/

Loading
Liquids
Concentrates
for
Airblast
Applications
(
1c)
grapes
0.125
40
1200
32000
33000
87000
110000
100000
140000
240000
Mixing/

Loading
Wettable
Powders
for
Aerial
Applications
(
2a)
apples,
Christmas
trees,
pears
0.25
350
30
60
61
250
420
260
450
7400
grapes
0.188
350
39
80
81
330
550
350
600
9800
turf
(
sod
farm)
5.4
350
1.4
2.8
2.8
12
19
12
21
340
Table
9.2
Combined
Dermal
/
Inhalation
Exposure
Scenario
Crop
or
Target
App
Rate
(
lb
ai/
acre)
a
Area
Treated
Daily
(
acre)
b
Combined
MOEsj
Baselinec
Dermal
+

Baseline
Inh
Single
layer
w/
glovesd
Dermal
+

Baseline
Inh
Double
layer
w/

glovese
Dermal
+

Baseline
Inh
Single
layer
w/
gloves
Dermal
+

80%
Rf
Inh
Single
layer
w/
gloves
Dermal
+

90%
Rg
Inh
Double
layer
w/

gloves
Dermal
+

80%
R
Inh
Double
layer
w/

gloves
Dermal
+

90%
R
Inh
Eng
Controli
Dermal
+

Inh
Page
79
of
105
Mixing/

Loading
Wettable
Powders
for
Aerial
Applications
(
2a)

(
cont.)
pine
seedlings
0.5
350
15
30
30
130
210
130
230
3700
Mixing/

Loading
Wettable
Powders
for
Chemigation
Applications
(
2b)
azaleas
0.005
lb
ai/
gallon
2400
gallons
220
440
440
1800
3000
1900
3300
54000
turf
(
sod
farm)
5.4
350
1.4
2.8
2.8
12
19
12
21
340
ornamentals
(
flowering,

shrubs,
trees)
0.25
60
170
350
350
1500
2400
1500
2600
43000
Mixing/

Loading
Wettable
Powders
for
Groundboom
Applications
(
2c)
azaleas
0.005
lb
ai/
gallon
16000
gallons
32
66
67
270
450
290
490
8000
grapes
0.188
80
170
350
350
1500
2400
1500
2600
43000
ornamentals
(
flowering,

shrubs,
trees)
0.25
40
260
530
530
2200
3600
2300
4000
64000
pine
seedlings
0.5
80
65
130
130
550
910
580
990
16000
turf
(
sod
farm)
5.4
80
6
12
12
51
84
53
92
1500
Table
9.2
Combined
Dermal
/
Inhalation
Exposure
Scenario
Crop
or
Target
App
Rate
(
lb
ai/
acre)
a
Area
Treated
Daily
(
acre)
b
Combined
MOEsj
Baselinec
Dermal
+

Baseline
Inh
Single
layer
w/
glovesd
Dermal
+

Baseline
Inh
Double
layer
w/

glovese
Dermal
+

Baseline
Inh
Single
layer
w/
gloves
Dermal
+

80%
Rf
Inh
Single
layer
w/
gloves
Dermal
+

90%
Rg
Inh
Double
layer
w/

gloves
Dermal
+

80%
R
Inh
Double
layer
w/

gloves
Dermal
+

90%
R
Inh
Eng
Controli
Dermal
+

Inh
Page
80
of
105
Mixing/

Loading
Wettable
Powders
for
Groundboom
Applications
(
2c)

(
cont.)
turf
(
golf
course)
5.4
40
12
24
25
100
170
110
180
3000
raspberries
0.125
80
260
530
530
2200
3600
2300
4000
64000
Mixing/

Loading
Wettable
Powders
to
Support
LCO
Handgun
Applications
(
mixing/
loading
supports
20
LCOs)

(
2d)
turf
(
LCO)
5.4
100
4.8
9.7
9.9
41
67
43
73
1200
Mixing/

Loading
Wettable
Powders
for
Airblast
Applications
(
2e)
apples,
Christmas
trees,
pears
0.25
40
260
530
530
2200
3600
2300
4000
64000
grapes
0.188
40
340
700
710
2900
4800
3100
5300
86000
pine
seedlings
0.5
40
130
260
270
1100
1800
1200
2000
32000
raspberries
0.125
40
520
1100
1100
4400
7300
4600
7900
130000
Table
9.2
Combined
Dermal
/
Inhalation
Exposure
Scenario
Crop
or
Target
App
Rate
(
lb
ai/
acre)
a
Area
Treated
Daily
(
acre)
b
Combined
MOEsj
Baselinec
Dermal
+

Baseline
Inh
Single
layer
w/
glovesd
Dermal
+

Baseline
Inh
Double
layer
w/

glovese
Dermal
+

Baseline
Inh
Single
layer
w/
gloves
Dermal
+

80%
Rf
Inh
Single
layer
w/
gloves
Dermal
+

90%
Rg
Inh
Double
layer
w/

gloves
Dermal
+

80%
R
Inh
Double
layer
w/

gloves
Dermal
+

90%
R
Inh
Eng
Controli
Dermal
+

Inh
Page
81
of
105
Mixing/

Loading
Wettable
Powders
to
Support
Rights­
of­
way
(
2f)
turf
(

rightsof
way)
5.4
80
6
12
12
51
84
53
92
1500
Mixing/

Loading
Dry
Flowables
for
Aerial
Applications
(
3a)
turf
(
sod
farm)
2.7
350
150
150
180
250
270
320
360
680
Mixing/

Loading
Dry
Flowables
for
Chemigation
Applications
(
3b)
azaleas
0.005
lb
ai/
gallon
2400
gallons
12000
12000
14000
19000
21000
26000
28000
54000
turf
(
sod
farm)
2.7
350
150
150
180
250
270
320
360
680
ornamentals
(
flowering,

shrubs,
trees)
0.25
60
9700
9700
11000
15000
17000
20000
23000
43000
Mixing/

Loading
Dry
Flowables
for
Groundboom
Applications
(
3c)
azaleas
0.005
lb
ai/
gallon
16000
gallons
1800
1800
2100
2900
3100
3800
4300
8000
turf
(
sod
farm)
2.7
80
670
670
790
1100
1200
1400
1600
3000
Table
9.2
Combined
Dermal
/
Inhalation
Exposure
Scenario
Crop
or
Target
App
Rate
(
lb
ai/
acre)
a
Area
Treated
Daily
(
acre)
b
Combined
MOEsj
Baselinec
Dermal
+

Baseline
Inh
Single
layer
w/
glovesd
Dermal
+

Baseline
Inh
Double
layer
w/

glovese
Dermal
+

Baseline
Inh
Single
layer
w/
gloves
Dermal
+

80%
Rf
Inh
Single
layer
w/
gloves
Dermal
+

90%
Rg
Inh
Double
layer
w/

gloves
Dermal
+

80%
R
Inh
Double
layer
w/

gloves
Dermal
+

90%
R
Inh
Eng
Controli
Dermal
+

Inh
Page
82
of
105
Mixing/

Loading
Dry
Flowables
for
Groundboom
Applications
(
3c)

(
cont.)
turf
(
golf
course)
2.7
40
1300
1300
1600
2100
2300
2800
3200
6000
ornamentals
(
flowering,

shrubs,
trees)
0.25
40
14000
14000
17000
23000
25000
31000
34000
64000
Mixing/

Loading
Dry
Flowables
to
Support
LCO
Handgun
Applications
(
mixing/
loading
supports
20
LCOs)

(
3d)
turf
(
LCO)
2.7
5
11000
11000
13000
17000
19000
23000
25000
48000
Loading
Granulars
for
Aerial
Applications
(
4a)
turf
(
sod
farm)
2.6
350
140
150
150
610
1000
680
1200
7200
Loading
Granulars
for
Tractor
Drawn
Spreader
Applications
(
4b)
turf
(
sod
farm)
2.6
80
630
640
660
2700
4400
3000
5300
32000
turf
(
golf
course)
1.36
40
2400
2400
2500
10000
17000
11000
20000
120000
Applicator
Applying
Sprays
via
Aerial
Equipment
(
5)
apples,
Christmas
trees,
pears
0.25
350
No
Data
No
Data
No
Data
No
Data
No
Data
No
Data
No
Data
20000
Table
9.2
Combined
Dermal
/
Inhalation
Exposure
Scenario
Crop
or
Target
App
Rate
(
lb
ai/
acre)
a
Area
Treated
Daily
(
acre)
b
Combined
MOEsj
Baselinec
Dermal
+

Baseline
Inh
Single
layer
w/
glovesd
Dermal
+

Baseline
Inh
Double
layer
w/

glovese
Dermal
+

Baseline
Inh
Single
layer
w/
gloves
Dermal
+

80%
Rf
Inh
Single
layer
w/
gloves
Dermal
+

90%
Rg
Inh
Double
layer
w/

gloves
Dermal
+

80%
R
Inh
Double
layer
w/

gloves
Dermal
+

90%
R
Inh
Eng
Controli
Dermal
+

Inh
Page
83
of
105
grapes
0.188
350
No
Data
No
Data
No
Data
No
Data
No
Data
No
Data
No
Data
27000
turf
(
sod
farm)
5.4
350
No
Data
No
Data
No
Data
No
Data
No
Data
No
Data
No
Data
940
pine
seedlings
0.5
350
No
Data
No
Data
No
Data
No
Data
No
Data
No
Data
No
Data
10000
Applying
Sprays
via
Aerial
Equipment
(
5)

(
cont.)
turf
(
sod
farm)
2.7
350
No
Data
No
Data
No
Data
No
Data
No
Data
No
Data
No
Data
1900
grapes
0.125
350
No
Data
No
Data
No
Data
No
Data
No
Data
No
Data
No
Data
41000
Applying
Granulars
via
Aerial
Equipment
(
6)
turf
(
sod
farm)
2.6
350
No
Data
No
Data
No
Data
No
Data
No
Data
No
Data
No
Data
200
Applying
Sprays
via
Groundboom
Equipment
(
7)
azaleas
0.005
lb
ai/
gallon
16000
gallons
3200
3200
3400
8900
11000
10000
14000
27000
grapes
0.125
80
26000
26000
27000
71000
92000
81000
110000
220000
grapes
0.188
80
17000
17000
18000
48000
61000
54000
72000
150000
turf
(
sod
farm)
5.4
80
600
600
620
1700
2100
1900
2500
5000
Table
9.2
Combined
Dermal
/
Inhalation
Exposure
Scenario
Crop
or
Target
App
Rate
(
lb
ai/
acre)
a
Area
Treated
Daily
(
acre)
b
Combined
MOEsj
Baselinec
Dermal
+

Baseline
Inh
Single
layer
w/
glovesd
Dermal
+

Baseline
Inh
Double
layer
w/

glovese
Dermal
+

Baseline
Inh
Single
layer
w/
gloves
Dermal
+

80%
Rf
Inh
Single
layer
w/
gloves
Dermal
+

90%
Rg
Inh
Double
layer
w/

gloves
Dermal
+

80%
R
Inh
Double
layer
w/

gloves
Dermal
+

90%
R
Inh
Eng
Controli
Dermal
+

Inh
Page
84
of
105
turf
(
golf
course)
5.4
40
1200
1200
1200
3300
4300
3800
5000
10000
turf
(
sod
farm)
2.7
80
1200
1200
1200
3300
4300
3800
5000
10000
turf
(
golf
course)
2.7
40
2400
2400
2500
6600
8500
7500
10000
20000
raspberries
0.125
80
26000
26000
27000
71000
92000
81000
110000
220000
Applying
Sprays
via
Groundboom
Equipment
(
7)

(
cont.)
pine
seedlings
0.5
80
6400
6400
6700
18000
23000
20000
27000
55000
ornamentals
(
flowering,

shrubs,
trees)
0.25
40
26000
26000
27000
71000
92000
81000
110000
220000
turf
(
sod
farm)
0.64
80
5000
5000
5200
14000
18000
16000
21000
43000
turf
(
golf
course)
0.64
40
10000
10000
10000
28000
36000
32000
42000
85000
Applying
Sprays
via
Airblast
Equipment
(
8)
apples,
Christmas
trees,
pears
0.25
40
2600
3100
3200
(
3500
­

HGh)
5800
6600
6200
(
7600
­
HG)
7100
(
8800
­
HG)
34000
pine
seedlings
0.5
40
1300
1600
1600
(
1600
­
HG)
2900
3300
3100
(
3800
­
HG)
3500
(
4400
­
HG)
17000
grapes
0.188
40
3400
4100
4300
7800
8700
8300
9400
45000
Table
9.2
Combined
Dermal
/
Inhalation
Exposure
Scenario
Crop
or
Target
App
Rate
(
lb
ai/
acre)
a
Area
Treated
Daily
(
acre)
b
Combined
MOEsj
Baselinec
Dermal
+

Baseline
Inh
Single
layer
w/
glovesd
Dermal
+

Baseline
Inh
Double
layer
w/

glovese
Dermal
+

Baseline
Inh
Single
layer
w/
gloves
Dermal
+

80%
Rf
Inh
Single
layer
w/
gloves
Dermal
+

90%
Rg
Inh
Double
layer
w/

gloves
Dermal
+

80%
R
Inh
Double
layer
w/

gloves
Dermal
+

90%
R
Inh
Eng
Controli
Dermal
+

Inh
Page
85
of
105
(
4700
­
HG)
(
10000
­

HG)
(
12000
­

HG)

Applying
Sprays
via
Airblast
Equipment
(
8)

(
cont.)
grapes,
raspberries
0.125
40
5100
6200
6400
(
7100
­
HG)
12000
13000
12000
(
15000
­

HG)
14000
(
18000
­

HG)
68000
Applying
Sprays
via
Handgun
Equipment
(
9)
turf
(
LCO)
5.4
5
No
Data
1500
2300
1800
1900
3200
3300
No
Data
turf
(
LCO)
2.7
5
No
Data
3000
4500
3700
3800
6300
6600
No
Data
Applying
Sprays
via
Rights
of
Way
Equipment
(
10)
turf
(

rightsof
way)
5.4
80
26
61
71
93
99
120
130
No
Data
Applying
Granulars
via
Tractor
Drawn
Spreader
(
11)
turf
(
sod
farm)
2.6
80
860
880
910
3400
5300
3900
6500
4600
turf
(
golf
course)
1.36
40
3300
3400
3500
13000
20000
15000
25000
18000
Flagger
Flagging
for
Aerial
Sprays
Applications
(
12)
apples,
Christmas
trees,
pears
0.25
350
5500
No
Data
5600
No
Data
No
Data
13000
16000
270000
grapes
0.125
350
11000
No
Data
11000
No
Data
No
Data
27000
33000
550000
grapes
0.188
350
7300
No
Data
7500
No
Data
No
Data
18000
22000
370000
turf
(
sod
5.4
350
250
No
Data
260
No
Data
No
Data
620
750
13000
Table
9.2
Combined
Dermal
/
Inhalation
Exposure
Scenario
Crop
or
Target
App
Rate
(
lb
ai/
acre)
a
Area
Treated
Daily
(
acre)
b
Combined
MOEsj
Baselinec
Dermal
+

Baseline
Inh
Single
layer
w/
glovesd
Dermal
+

Baseline
Inh
Double
layer
w/

glovese
Dermal
+

Baseline
Inh
Single
layer
w/
gloves
Dermal
+

80%
Rf
Inh
Single
layer
w/
gloves
Dermal
+

90%
Rg
Inh
Double
layer
w/

gloves
Dermal
+

80%
R
Inh
Double
layer
w/

gloves
Dermal
+

90%
R
Inh
Eng
Controli
Dermal
+

Inh
Page
86
of
105
farm)

turf
(
sod
farm)
2.7
350
510
No
Data
520
No
Data
No
Data
1200
1500
25000
pine
seedlings
0.5
350
2700
No
Data
2800
No
Data
No
Data
6700
8100
140000
Flagging
for
Aerial
Granular
Applications
(
13)
turf
(
sod
farm)
2.6
350
1400
No
Data
1500
No
Data
No
Data
5100
7200
70000
Mixer/
Loader/
Applicator
Mixing/
Loading/

Applying
Liquid
Concentrates
with
Low
Pressure
Handwand
(
ORETF)
(
14)
greenhouse
ornamentals
(
flowering,

shrubs,
trees)

(
non­
WPS)
0.00938
lb
ai/
gallon
40
gallons
3200
90000
No
Data
130000
140000
No
Data
No
Data
Not
Feasible
ornamentals
(
flowering,

shrubs,

trees);
Pine
(
Christmas
tree?)
0.0023
lb
ai/
gallon
40
gallons
13000
370000
No
Data
530000
560000
No
Data
No
Data
Not
Feasible
roses
0.00029
lb
ai/
gallon
40
gallons
100000
2900000
No
Data
4200000
4400000
No
Data
No
Data
Not
Feasible
turf
(
LCO
&
0.64
5
370
11000
No
Data
15000
16000
No
Data
No
Data
Not
Feasible
Table
9.2
Combined
Dermal
/
Inhalation
Exposure
Scenario
Crop
or
Target
App
Rate
(
lb
ai/
acre)
a
Area
Treated
Daily
(
acre)
b
Combined
MOEsj
Baselinec
Dermal
+

Baseline
Inh
Single
layer
w/
glovesd
Dermal
+

Baseline
Inh
Double
layer
w/

glovese
Dermal
+

Baseline
Inh
Single
layer
w/
gloves
Dermal
+

80%
Rf
Inh
Single
layer
w/
gloves
Dermal
+

90%
Rg
Inh
Double
layer
w/

gloves
Dermal
+

80%
R
Inh
Double
layer
w/

gloves
Dermal
+

90%
R
Inh
Eng
Controli
Dermal
+

Inh
Page
87
of
105
golf
course)

grapes
0.125
lb
ai/
gallon
40
gallons
240
6700
No
Data
9700
10000
No
Data
No
Data
Not
Feasible
Mixing/
Loading/

Applying
Wettable
Powders
with
Low
Pressure
Handwand
(
PHED)
(
15)
apples
0.00062
lb
ai/
gallon
40
gallons
No
Data
7900
8100
29000
43000
32000
50000
Not
Feasible
Mixing/
Loading/

Applying
Wettable
Powders
with
Low
Pressure
Handwand
(
PHED)
(
15)

(
cont.)
azaleas
0.005
lb
ai/
gallon
40
gallons
No
Data
980
1000
3600
5300
3900
6200
Not
Feasible
grapes
0.00094
lb
ai/
gallon
40
gallons
No
Data
5200
5400
19000
28000
21000
33000
Not
Feasible
greenhouse
ornamentals
(
flowering,

shrubs,
trees)

(
non­
WPS)
0.00625
lb
ai/
gallon
40
gallons
No
Data
780
810
2900
4300
3200
5000
Not
Feasible
turf
(
LCO
&

golf
course)
5.4
5
No
Data
7.3
7.5
26
39
29
46
Not
Feasible
ornamentals
(
flowering,
0.0025
lb
40
gallons
No
Data
2000
2000
7100
11000
7900
12000
Not
Feasible
Table
9.2
Combined
Dermal
/
Inhalation
Exposure
Scenario
Crop
or
Target
App
Rate
(
lb
ai/
acre)
a
Area
Treated
Daily
(
acre)
b
Combined
MOEsj
Baselinec
Dermal
+

Baseline
Inh
Single
layer
w/
glovesd
Dermal
+

Baseline
Inh
Double
layer
w/

glovese
Dermal
+

Baseline
Inh
Single
layer
w/
gloves
Dermal
+

80%
Rf
Inh
Single
layer
w/
gloves
Dermal
+

90%
Rg
Inh
Double
layer
w/

gloves
Dermal
+

80%
R
Inh
Double
layer
w/

gloves
Dermal
+

90%
R
Inh
Eng
Controli
Dermal
+

Inh
Page
88
of
105
shrubs,
trees)
ai/
gallon
pears
0.00062
lb
ai/
gallon
40
gallons
No
Data
7900
8100
29000
43000
32000
50000
Not
Feasible
pine
seedlings
0.5
5
No
Data
78
81
290
430
320
500
Not
Feasible
Mixing/
Loading/

Applying
Dry
Flowables
with
Low
Pressure
Handwand
(
using
liquids
ORETF
data)
(
16)
azaleas
0.005
lb
ai/
gallon
40
gallons
5900
170000
No
Data
240000
260000
No
Data
No
Data
Not
Feasible
ornamentals
(
flowering,

shrubs,
trees)
0.0025
lb
ai/
gallon
40
gallons
12000
340000
No
Data
490000
510000
No
Data
No
Data
Not
Feasible
turf
(
LCO
&

golf
course)
2.7
5
88
2500
No
Data
3600
3800
No
Data
No
Data
Not
Feasible
Mixing/
Loading/

Applying
Liquid
Concentrates
with
a
Handgun
Sprayer
(
LCO
ORETF
data)

(
17)
greenhouse
ornamentals
(
flowering,

shrubs,
trees)

(
non­
WPS)
0.00938
lb
ai/
gallon
1000
gallons
No
Data
3400
5400
4000
4200
7000
7500
Not
Feasible
ornamentals
(
flowering,

shrubs,

trees);
Pine
(
Christmas
tree?)
0.0023
lb
ai/
gallon
1000
gallons
No
Data
14000
22000
16000
17000
29000
31000
Not
Feasible
Table
9.2
Combined
Dermal
/
Inhalation
Exposure
Scenario
Crop
or
Target
App
Rate
(
lb
ai/
acre)
a
Area
Treated
Daily
(
acre)
b
Combined
MOEsj
Baselinec
Dermal
+

Baseline
Inh
Single
layer
w/
glovesd
Dermal
+

Baseline
Inh
Double
layer
w/

glovese
Dermal
+

Baseline
Inh
Single
layer
w/
gloves
Dermal
+

80%
Rf
Inh
Single
layer
w/
gloves
Dermal
+

90%
Rg
Inh
Double
layer
w/

gloves
Dermal
+

80%
R
Inh
Double
layer
w/

gloves
Dermal
+

90%
R
Inh
Eng
Controli
Dermal
+

Inh
Page
89
of
105
roses
0.00029
lb
ai/
gallon
1000
gallons
No
Data
110000
170000
130000
130000
230000
240000
Not
Feasible
Mixing/
Loading/

Applying
Wettable
Powders
with
a
Handgun
Sprayer
(
LCO
ORETF
data)

(
18)
apples
0.00062
lb
ai/
gallon
1000
gallons
No
Data
5100
5500
16000
23000
21000
32000
Not
Feasible
grapes
0.00094
lb
ai/
gallon
1000
gallons
No
Data
3400
3600
11000
15000
14000
21000
Not
Feasible
pine
seedlings
0.5
5
No
Data
1300
1400
4100
5600
5100
7900
Not
Feasible
Mixing/
Loading/

Applying
Water
Soluble
Bags
with
Handgun
Sprayer
(
LCO
ORETF
data)

(
19)
greenhouse
ornamentals
(
flowering,

shrubs,
trees)

(
non­
WPS)
0.00625
lb
ai/
gallon
1000
gallons
No
Data
2400
3100
3800
4100
6000
6800
Not
Feasible
turf
(
LCO
&

golf
course)
5.4
5
No
Data
560
730
890
960
1400
1600
Not
Feasible
pine
seedlings
0.5
5
No
Data
6100
7900
9600
10000
15000
17000
Not
Feasible
Table
9.2
Combined
Dermal
/
Inhalation
Exposure
Scenario
Crop
or
Target
App
Rate
(
lb
ai/
acre)
a
Area
Treated
Daily
(
acre)
b
Combined
MOEsj
Baselinec
Dermal
+

Baseline
Inh
Single
layer
w/
glovesd
Dermal
+

Baseline
Inh
Double
layer
w/

glovese
Dermal
+

Baseline
Inh
Single
layer
w/
gloves
Dermal
+

80%
Rf
Inh
Single
layer
w/
gloves
Dermal
+

90%
Rg
Inh
Double
layer
w/

gloves
Dermal
+

80%
R
Inh
Double
layer
w/

gloves
Dermal
+

90%
R
Inh
Eng
Controli
Dermal
+

Inh
Page
90
of
105
Mixing/
Loading/

Applying
Dry
Flowables
Concentrates
with
a
Handgun
Sprayer
(
LCO
ORETF
data)

(
20)
turf
(
LCO
&

golf
course)
2.7
5
No
Data
590
670
1500
1800
2000
2700
Not
Feasible
Mixing/
Loading/

Applying
Liquid
Concentrates
with
a
High
Pressure
Handwand
(
only
study
in
PHED
is
for
greenhouse
use)

(
21)
greenhouse
ornamentals
(
flowering,

shrubs,
trees)

(
non­
WPS)
0.00938
lb
ai/
gallon
1000
gallons
No
Data
170
180
440
560
560
770
Not
Feasible
ornamentals
(
flowering,

shrubs,
trees)
0.0023
lb
ai/
gallon
1000
gallons
No
Data
680
730
1800
2300
2300
3100
Not
Feasible
roses
0.00029
lb
ai/
gallon
1000
gallons
No
Data
5400
5800
14000
18000
18000
25000
Not
Feasible
Table
9.2
Combined
Dermal
/
Inhalation
Exposure
Scenario
Crop
or
Target
App
Rate
(
lb
ai/
acre)
a
Area
Treated
Daily
(
acre)
b
Combined
MOEsj
Baselinec
Dermal
+

Baseline
Inh
Single
layer
w/
glovesd
Dermal
+

Baseline
Inh
Double
layer
w/

glovese
Dermal
+

Baseline
Inh
Single
layer
w/
gloves
Dermal
+

80%
Rf
Inh
Single
layer
w/
gloves
Dermal
+

90%
Rg
Inh
Double
layer
w/

gloves
Dermal
+

80%
R
Inh
Double
layer
w/

gloves
Dermal
+

90%
R
Inh
Eng
Controli
Dermal
+

Inh
Page
91
of
105
Mixing/
Loading/

Applying
Dry
Flowables
with
a
High
Pressure
Handwand
(
only
study
in
PHED
is
for
greenhouse
use
for
liquid
concentrates)
(
22)
azaleas
0.005
lb
ai/
gallon
1000
gallons
No
Data
310
340
830
1100
1100
1400
Not
Feasible
ornamentals
(
flowering,

shrubs,
trees)
0.0025
lb
ai/
gallon
1000
gallons
No
Data
620
670
1700
2100
2100
2900
Not
Feasible
Mixing/
Loading/

Applying
Wettable
Powders
with
a
High
Pressure
Handwand
(
only
study
in
PHED
is
for
greenhouse
use
for
liquid
concentrates)
(
23)
ornamentals
(
flowering,

shrubs,
trees)
0.0025
lb
ai/
gallon
1000
gallons
No
Data
620
670
1700
2100
2100
2900
Not
Feasible
Table
9.2
Combined
Dermal
/
Inhalation
Exposure
Scenario
Crop
or
Target
App
Rate
(
lb
ai/
acre)
a
Area
Treated
Daily
(
acre)
b
Combined
MOEsj
Baselinec
Dermal
+

Baseline
Inh
Single
layer
w/
glovesd
Dermal
+

Baseline
Inh
Double
layer
w/

glovese
Dermal
+

Baseline
Inh
Single
layer
w/
gloves
Dermal
+

80%
Rf
Inh
Single
layer
w/
gloves
Dermal
+

90%
Rg
Inh
Double
layer
w/

gloves
Dermal
+

80%
R
Inh
Double
layer
w/

gloves
Dermal
+

90%
R
Inh
Eng
Controli
Dermal
+

Inh
Page
92
of
105
Mixing/
Loading/

Applying
Wettable
Powders
with
a
High
Pressure
Handwand
(
only
study
in
PHED
is
for
greenhouse
use
for
liquid
concentrates)
(
23)

(
cont.)
azaleas
0.005
lb
ai/
gallon
1000
gallons
No
Data
310
340
830
1100
1100
1400
Not
Feasible
greenhouse
ornamentals
(
flowering,

shrubs,
trees)

(
non­
WPS)
0.00625
lb
ai/
gallon
1000
gallons
No
Data
250
270
670
850
840
1100
Not
Feasible
Mixing/
Loading/

Applying
Liquids
with
an
Injector
(
24)
ornamentals
(
shade
trees,

woody
shrubs)
0.00007
5
lb
ai/
1
inch
of
trunk
inch
of
trunk
No
Data
No
Data
No
Data
No
Data
No
Data
No
Data
No
Data
Not
Feasible
Mixing/
Loading/

Applying
RTU
Briquette
(
25)
pine
seedlings
0.00019
lb
ai/
seedling
seedlin
gs
No
Data
No
Data
No
Data
No
Data
No
Data
No
Data
No
Data
No
Data
Mixing/
Loading/

Applying
Dip
(
26)
pine
seed
(
nurseries)
0.00006
25
lb
ai/
gallon
gallons
No
Data
No
Data
No
Data
No
Data
No
Data
No
Data
No
Data
No
Data
pineapple
(
postharvest
0.0028
lb
ai/
gallon
gallons
No
Data
No
Data
No
Data
No
Data
No
Data
No
Data
No
Data
No
Data
Table
9.2
Combined
Dermal
/
Inhalation
Exposure
Scenario
Crop
or
Target
App
Rate
(
lb
ai/
acre)
a
Area
Treated
Daily
(
acre)
b
Combined
MOEsj
Baselinec
Dermal
+

Baseline
Inh
Single
layer
w/
glovesd
Dermal
+

Baseline
Inh
Double
layer
w/

glovese
Dermal
+

Baseline
Inh
Single
layer
w/
gloves
Dermal
+

80%
Rf
Inh
Single
layer
w/
gloves
Dermal
+

90%
Rg
Inh
Double
layer
w/

gloves
Dermal
+

80%
R
Inh
Double
layer
w/

gloves
Dermal
+

90%
R
Inh
Eng
Controli
Dermal
+

Inh
Page
93
of
105
Loading/

Applying
Granulars
via
Push
Type
Spreader
(
ORETF)

(
27)
turf
(
golf
course)
1.36
5
2900
3400
4000
8000
9600
12000
16000
Not
Feasible
a
Application
rates
are
the
maximum
application
rates
determined
from
EPA
registered
labels
for
triadimefon
b
Amount
handled
per
day
values
are
HED
estimates
of
acres
treated
per
day
based
on
Exposure
SAC
SOP
#
9
"
Standard
Values
for
Daily
Acres
Treated
in
Agriculture,"
industry
sources,
and
HED
estimates.

c
Baseline
=
No
gloves
and
no
respirator
d
Single
layer
w/
gloves
is
baseline
attire
plus
chemical­
resistant
gloves.

e
Double
layer
w/
gloves
is
coveralls
worn
over
long­
sleeve
shirt
and
long
pants,
plus
chemical­
resistant
gloves.

f
80%
Respirator
is
quarter­
face
dust/
mist
respirator
(
that
provides
an
80%
protection
factor).

g
90%
Respirator
is
half­
face
dust/
mist
respirator
(
that
provides
a
90%
protection
factor).

h
Double
layer
w/
gloves
and
headgear:
Coverall
worn
over
long­
sleeve
shirt
and
long
pants
plus
chemical
resistant
gloves
and
headgear.

i
Engineering
control
is
closed
mixing/
loading
system,
enclosed
cab,
or
enclosed
cockpit.

j
Combined
MOEs
=
1/[(
1/
Dermal
MOE)
+
(/
Inhalation
MOE)]
Page
94
of
105
Table
9.3
Combined
Estimated
Handler
Dermal
and
Inhalation
Risk
from
Commercial
Seed
Treatment
Pine
Seed
Exposure
Scenario
App
Ratea
(
lb
ai/
lb)
Amount
Handled
per
day
b
(
lb
ai/
day)
Combined
MOEsi
Baselinec
Dermal
+

Baseline
Inh
Single
layer
w/

glovesd
Dermal
+

Baseline
Inh
Double
layer
w/

glovese
Dermal
+

Baseline
Inh
Baseline
Dermal
+

80%
Rg
Inh
Double
layer
w/

gloves
Dermal
+

80%
R
Inh
Baseline
Dermal
+

90%
Rg
Inh
Double
layer
w/

gloves
Dermal
+

90%
R
Inh
Eng
Controlh
Dermal
+

Inh
Ponderosa
Seedj
Loader/
Applicator
0.0013
16.23
0.34
0.34
0.34
1.7
1.7
3.4
3.4
43
Sewer
0.0013
16.23
64
No
Data
No
Data
320
No
Data
640
No
Data
No
Data
Bagger
0.0013
16.23
92
No
Data
No
Data
460
No
Data
910
No
Data
No
Data
Multiple
Activies
0.0013
16.23
No
Data
9.2
No
Data
No
Data
46
No
Data
91
No
Data
a
Application
rates
are
the
maximum
application
rates
determined
from
EPA
registered
labels
for
triadimefon
b
Amount
handled
per
day
calculated
from
the
maximum
application
rate
and
the
lbs
of
seed
treated
or
planted/
day
and:
for
ponderosa
seed
­
12485
lb/
day.

c
Baseline
=
No
gloves
and
no
respirator
d
Single
layer
w/
gloves
is
baseline
attire
plus
chemical­
resistant
gloves.

e
Double
layer
w/
gloves
is
coveralls
worn
over
long­
sleeve
shirt
and
long
pants,
plus
chemical­
resistant
gloves.

f
80%
Respirator
is
quarter­
face
dust/
mist
respirator
(
that
provides
an
80%
protection
factor).

g
90%
Respirator
is
half­
face
dust/
mist
respirator
(
that
provides
a
90%
protection
factor).

h
Engineering
control
is
closed
mixing/
loading
system,
enclosed
cab,
or
enclosed
cockpit.

i
Combined
MOEs
=
1/[(
1/
Dermal
MOE)
+
(/
Inhalation
MOE)]

j
Ponderosa
pine
seeds
used.
Page
95
of
105
Table
9.4
Combined
Estimated
Handler
Dermal
and
Inhalation
Risk
from
Nursery
Seed
Treatment
Crop
Acres
treated/

day
App
Ratea
(
lb
ai/
lb)
Amount
Handled
per
dayb
(
lb
ai/
day)
Combined
MOEsi
Baselinec
Dermal
+

Baseline
Inh
Single
layer
w/

glovesd
Dermal
+

Baseline
Inh
Double
layer
w/

glovese
Dermal
+

Baseline
Inh
Single
layer
w/
gloves
Dermal
+

80%
Rf
Inh
Double
layer
w/

gloves
Dermal
+

80%
R
Inh
Single
layer
w/

gloves
Dermal
+

90%
Rg
Inh
Double
layer
w/

gloves
Dermal
+

90%
R
Inh
Eng
Controlh
Dermal
+

Inh
LOADING/
APPLYING
WITH
HOPPER
OR
PLANTER
BOX
SEED
TREATMENT
Pine
Seedj
80
0.0013
0.129840019
No
Data
1300
No
Data
4500
No
Data
6400
No
Data
No
Data
LOADING/
PLANTING
PREVIOUSLY
TREATED
SEEDS
Pine
Seedj
80
0.0013
0.129840019
No
Data
540
No
Data
2700
No
Data
5300
No
Data
No
Data
a
Application
rates
are
the
maximum
application
rates
determined
from
EPA
registered
labels
for
triadimefon
b
Amount
handled
per
day
calculated
from
the
acres
treated/
day
and
the
maximum
lb
of
seed
planted
per
acre:
for
ponderosa
seed
­
1.25
lb/
A.

c
Baseline
=
No
gloves
and
no
respirator
d
Single
layer
w/
gloves
is
baseline
attire
plus
chemical­
resistant
gloves.

e
Double
layer
w/
gloves
is
coveralls
worn
over
long­
sleeve
shirt
and
long
pants,
plus
chemical­
resistant
gloves.

f
80%
Respirator
is
quarter­
face
dust/
mist
respirator
(
that
provides
an
80%
protection
factor).

g
90%
Respirator
is
half­
face
dust/
mist
respirator
(
that
provides
a
90%
protection
factor).

h
Engineering
control
is
closed
mixing/
loading
system,
enclosed
cab,
or
enclosed
cockpit.

i
Combined
MOEs
=
1/[(
1/
Dermal
MOE)
+
(/
Inhalation
MOE)]

j
Ponderosa
pine
seeds
used.
Page
96
of
105
9.8
Occupational
Handler
Risk
Summary
For
all
exposure
scenarios,
except
one,
the
dermal
and
inhalation
risk
estimates
met
(
or
exceeded)
the
target
MOE
level
of
100
at
some
level
of
risk
mitigation.
Based
on
PHED
data,
the
estimated
inhalation
risk
for
following
scenario
remains
a
concern
with
maximum
inhalation
risk
mitigation:
mixng/
loading/
applying
wettable
powders
with
a
low
pressure
handwand
to
turf
(
the
dermal
MOE
=
110
with
double
layer
and
gloves;
however
the
inhalation
MOE
=
80
with
a
90%
protection
factor
half­
face
respirator);.

In
all
nursery
seed­
treatment
scenarios,
dermal
and
inhalation
MOEs
met
or
exceeded
the
target
MOE
of
100
at
some
level
of
risk
mitigation.
For
commercial
seed
treatment,
all
dermal
MOEs
met
or
exceeded
the
the
target
MOE
of
100
at
some
level
of
mitigation.
However,
inhalation
exposure
remains
a
concern
for
two
scenarios
(
even
with
maximum
inhalation
risk
mitigation):
1)
loader/
applicator
for
ponderosa
pine
seed,
where
inhalation
MOE
=
43
with
engineering
controls);
and
2)
multiple
activities
for
ponderosa
pine
seed,
where
inhalation
MOE
=
92
with
a
90%
protection
factor
half­
face
respirator.

For
all
exposure
scenarios,
except
one,
the
combined
dermal
and
inhalation
risk
estimates
met
or
exceeded
the
target
MOE
of
100
at
some
level
of
risk
mitigation.
Based
on
PHED
data,
the
following
scenario
remains
a
concern
with
maximum
dermal
and
inhalation
risk
mitigation:
mixing/
loading/
applying
wettable
powders
with
a
low
pressure
handwand
to
turf
(
LCO
and
golf
course),
where
the
MOE
=
46
with
a
double
layer,
gloves,
and
a
90%
protection
factor
half­
face
respirator.

In
all
nursery
seed­
treatment
scenarios,
combined
dermal
and
inhalation
MOEs
met
or
exceeded
the
target
MOE
of
100
at
some
level
of
risk
mitigation.
For
commercial
seed
treatment,
two
scenarios
remain
a
concern
even
with
maximum
mitigation:
1)
loader/
applicator
for
ponderosa
pine
seed,
where
inhalation
MOE
=
43
with
engineering
controls);
and
2)
multiple
activities
for
ponderosa
pine
seed,
where
inhalation
MOE
=
92
with
a
90%
protection
factor
half­
face
respirator.

9.9
Occupational
Postapplication
Exposure
The
term
"
postapplication"
is
used
to
describe
exposures
to
individuals
that
occur
as
a
result
of
being
in
an
area
that
has
been
treated
with
a
pesticide
(
also
referred
to
as
reentry
exposure).
Job
requirements
(
e.
g.,
the
kinds
of
jobs
to
cultivate
a
crop),
the
nature
of
the
crop,
or
target,
that
was
treated,
and
how
the
chemical
residues
degrade
in
the
environment
can
cause
exposure
levels
to
differ
over
time.
Each
factor
has
been
considered
in
this
assessment.
Triadimefon
is
applied
to:
grapes,
turf
(
including
sod
farm
turf),
ornamentals,
apples,
pears,
Christmas
trees,
and
raspberries.

"
Transfer
coefficients"
are
used
to
numerically
represent
the
postapplication
exposures,
and
are
generally
presented
as
cm2/
hour.
A
transfer
coefficient
is
a
measure
of
the
residue
transferred
from
a
treated
surface
to
a
person
who
is
doing
a
task
or
activity
in
a
treated
area.
These
values
Page
97
of
105
are
the
ratio
of
an
exposure
for
a
given
task
or
activity
to
the
amount
of
pesticide
residue
on
treated
surfaces
available
for
transfer.
Also,
to
develop
a
postapplication
assessment,
HED
considers
the
types
of
tasks
and
activities
that
individuals
are
likely
to
be
doing
in
areas
recently
treated
with
a
pesticide.
Common
examples
include:
crop
harvesting
tasks
(
e.
g.,
harvesting
treated
turf),
crop
maintenance
tasks
(
e.
g.,
irrigating,
weeding,
and
mowing),
and
crop
advisor
tasks
(
e.
g.,
scouting).
Label
directions
and
other
use
data
are
considered
to
determine
application
rates
and
application
frequency.
When
appropriate
chemical­
and
crop­
specific
transferable
residue
data
are
unavailable,
a
standard
modeling
approach
to
predict
transferable
residues
over
time
is
used.
All
triadimefon
occupational
postapplication
scenarios
were
evaluated
using
HED's
default
assumptions
that
20
percent
of
the
initial
application
is
available
for
transfer
on
day
0
(
i.
e.,
12
hours
after
application)
and
that
the
residue
dissipates
at
a
rate
of
10
percent
per
day.

The
likely
frequency
and
duration
of
postapplication
occupational
exposures
to
triadimefon
is
also
assessed.
For
triadimefon,
the
exposure
durations
for
postapplication
risk
assessment
were
shortterm
(<
30
days)
and
intermediate­
term
(
greater
than
30
days
up
to
several
months).
However,
since
the
dermal
toxicological
endpoint
of
concern
is
the
same
for
short­
and
intermediate­
term
exposures,
the
short­
and
intermediate­
term
postapplication
risks
are
numerically
identical.
Inhalation
exposures
are
thought
to
be
negligible
in
outdoor
postapplication
scenarios,
since
triadimefon
has
low
vapor
pressure
and
the
dilution
factor
outdoors
is
considered
infinite.
In
addition,
under
the
Worker
Protection
Standard
for
Agricultural
Pesticides
 
WPS
 
(
40
CFR
170)
greenhouses
must
be
appropriately
ventilated
(
ventilation
criteria
are
provided)
following
pesticide
applications
so
that
postapplication
inhalation
exposures
are
minimal.
As
such,
inhalation
postapplication
exposures
are
not
considered
in
this
assessment.

A
Restricted
Entry
Interval,
or
REI,
is
used
to
mitigate
postapplication
exposure
following
applications
to
crops.
The
REI
is
the
time
period
following
a
pesticide
application
during
which
entry
into
the
treated
area
is
restricted
and
is
calculated
a
chemical­,
crop­,
and
activity­
specific
basis.
Triadimefon
uses
were
identified
for
the
following
agronomic
crop
groupings:

Flowers,
cut
(
ornamental),
Tree,
fruit,
evergreen,
Tree,
fruit,
deciduous,
Turf/
sod,
and
Vine/
trellis
(
with
and
without
girdling).

Within
each
agronomic
group,
a
variety
of
cultural
practices
are
required
to
maintain
the
included
crops.
These
practices
are
varied
and
typically
involve
light
to
heavy
contact
with
immature
plants
as
well
as
with
more
mature
plants.
No
triadimefon­
specific
turf
transferrable
residue
(
TTR)
data
or
dislodgeable
foliar
residue
(
DFR)
data
were
available.
Therefore,
this
assessment
uses
the
default
assumption
that
5
percent
of
the
application
rate
is
available
on
day
0
(
i.
e.,
12
hours
after
application)
and
the
residue
dissipates
at
a
rate
of
10
percent
per
day
for
turf
and
20
percent
of
the
application
rate
is
available
on
day
0
(
i.
e.,
12
hours
after
application)
and
the
residue
dissipates
at
a
rate
of
10
percent
per
day
for
all
other
crops.
Page
98
of
105
Page
99
of
105
Table
9.5
Postapplication
Exposure
/
Risk
Summary
Crop
Crop
Grouping
Application
rate
(
lb
ai/
acre)
Transfer
Coefficient
MOE
at
Day
0
Apples
Tree,
fruit,
deciduous
0.25
3000
(
Thinning)
1300
1500
(
Harvest
(
hand),
Propping,
Pruning
(
hand),
Training,
Tying)
2700
1000
(
Scouting,
Weeding
(
hand),
Irrigation)
4000
100
(
Propping)
40000
Christmas
trees
Tree,
fruit,
evergreen
0.25
8000
(
Bagging
Fruit,
Hand
Labor
(
misc.),
Harvest
(
hand),
Pollination,
Staking,
Topping,
Training,
Thinning,
Tying)
500
3000
(
Pruning
(
cones),
Pruning
(
hand),
Thinning,
Seed
Cone
Harvesting)
1300
1000
(
Irrigation,
Scouting,
Weeding
(
hand),
Thinning)
4000
100
(
Propping)
40000
Grapes
(
juice
and
wine)

Vine/
trellis
(
with
and
without
girdling)
0.188
5000
(
Harvest
(
hand),
Pruning
(
hand),
Training,
Tying,
Thinning,
Leaf
Pulling)
1100
1000
(
Scouting,
Training,
Tying)
5300
500
(
Irrigation,
Weeding
(
hand),
Scouting,
Hedging)
11000
Grapes
(
table
and
raisin)
0.188
10000
(
Girdling,
Cane
turning),
Cane
Tying
530
5000
(
Harvest
(
hand),
Pruning
(
hand),
Training,
Tying,
Thinning,
Leaf
Pulling)
1100
1000
(
Scouting,
Training,
Tying)
5300
500
(
Irrigation,
Weeding
(
hand),
Scouting,
Hedging)
11000
Table
9.5
Postapplication
Exposure
/
Risk
Summary
Crop
Crop
Grouping
Application
rate
(
lb
ai/
acre)
Transfer
Coefficient
MOE
at
Day
0
Page
100
of
105
Ornamental
flowers
Flowers,
cut
(
ornamental)
0.25
5100
(
cut
flowers
and
foliage)
790
400
(
all
other
nursery
crops)
10000
Pears
Tree,
fruit,
deciduous
0.25
3000
(
Thinning)
1300
1500
(
Harvest
(
hand),
Propping,
Pruning
(
hand),
Training,
Tying)
2700
1000
(
Scouting,
Weeding
(
hand),
Irrigation)
4000
100
(
Propping)
40000
Raspberries
Vine/
trellis
(
with
and
without
girdling).
0.125
5000
(
Harvest
(
hand),
Pruning
(
hand),
Training,
Tying,
Thinning,
Leaf
Pulling)
1600
1000
(
Scouting,
Training,
Tying)
8000
500
(
Irrigation,
Weeding
(
hand),
Scouting,
Hedging)
16000
Sod
Farms
and
Golf
Course
Turf
Turf/
sod
5.4
6800
(
Transplanting,
Weeding
(
hand),
Harvest
(
hand),
Harvest
(
mechanical))
110
3800
(
Mowing)
220
9.10
Occupational
Postapplication
Risk
Summary
The
occupational
postapplication
exposure
and
risk
assessment
for
agricultural
crop
uses
of
triadimefon
indicates
that
the
target
MOE
of
100
is
met
or
exceeded
at
day
0
(
i.
e.,
12
hours
after
application)
for
all
crops
and
all
postapplication
activities.
Page
101
of
105
10.0
HUMAN
INCIDENT
DATA
REVIEW
The
following
data
bases
were
consulted
for
the
poisoning
incident
data
on
triamefon:

1)
OPP
Incident
Data
System
(
IDS):
reports
of
incidents
from
various
sources,
including
registrants,
other
federal
and
state
health
and
environmental
agencies
and
individual
consumers,
submitted
to
OPP
since
1992.

2)
Poison
Control
Centers:
as
the
result
of
a
data
purchase
by
EPA,
OPP
received
Poison
Control
Center
data
covering
the
years
1993
through
1998
for
all
pesticides.
Most
of
the
national
Poison
Control
Centers
(
PCCs)
participate
in
a
national
data
collection
system,
the
Toxic
Exposure
Surveillance
System
which
obtains
data
from
about
65­
70
centers
at
hospitals
and
universities.
PCCs
provide
telephone
consultation
for
individuals
and
health
care
providers
on
suspected
poisonings,
involving
drugs,
household
products,
pesticides,
etc.

There
were
nine
reports
of
occupational
exposure
to
triadimefon
and
46
non­
occupational
exposures
from
1993
through
2003.
There
were
just
two
exposures
reported
from
any
type
of
exposure
to
triadimenon,
but
neither
had
medical
outcome
recorded
or
required
medical
care.
Of
the
46
non­
occupational
exposures,
13
occurred
in
children
under
six
years
of
age.
Of
the
total
20
cases
with
medically
determined
outcome,
11
reported
minor
medical
outcome.
Of
the
total
54
exposures
to
triadimefon,
just
four
were
seen
in
a
health
care
facility
and
none
required
hospitalization.
A
review
of
symptoms
revealed
almost
exclusively
irritation
effects
(
including
rash
and
erythema)
to
skin,
mouth,
throat,
and
eyes.
These
effects
were
reported
a
total
of
24
times
with
some
patients
reporting
two
or
more
of
these
symptoms.
There
were
four
cases
reporting
headache
and
two
reported
cough.
No
other
significant
symptoms
were
reported.

3)
California
Department
of
Pesticide
Regulation:
California
has
collected
uniform
data
on
suspected
pesticide
poisonings
since
1982.
Physicians
are
required,
by
statute,
to
report
to
their
local
health
officer
all
occurrences
of
illness
suspected
of
being
related
to
exposure
to
pesticides.
The
majority
of
the
incidents
involve
workers.
Information
on
exposure
(
worker
activity),
type
of
illness
(
systemic,
eye,
skin,
eye/
skin
and
respiratory),
likelihood
of
a
causal
relationship,
and
number
of
days
off
work
and
in
the
hospital
are
provided.

The
majority
of
triadimefon
incidents
(
92%)
occurred
prior
to
1990.
Most
of
the
triadimefon
cases
(
73%)
involved
use
on
grapes
which
is
a
labor
intensive
crop
involving
high
exposure
to
foliar
residues.
Foliar
residues
accounted
for
half
of
the
illnesses
and
nearly
half
of
the
systemic
illnesses.
Although
most
of
the
symptoms
appeared
to
be
minor,
skin
and
eye
irritation,
and
rash
were
among
the
most
common
topical
symptoms.
The
most
common
systemic
effects
included
nausea,
headache,
sneezing,
congestion,
difficulty
breathing
and
other
allergic­
type
reactions.
There
were
three
reports
of
vomiting.

4)
National
Pesticide
Information
Center
(
NPIC):
NPIC
is
a
toll­
free
information
service
supported
by
OPP.
A
ranking
of
the
top
200
active
ingredients
for
which
telephone
calls
were
Page
102
of
105
received
during
calendar
years
1984­
1991,
inclusive
has
been
prepared.
The
total
number
of
calls
was
tabulated
for
the
categories
human
incidents,
animal
incidents,
calls
for
information,
and
others.

On
the
list
of
the
top
200
chemicals
for
which
NPIC
received
calls
from
1984­
1991
inclusively,
triadimefon
was
not
reported
to
be
involved
in
human
incidents.

5)
National
Institute
of
Occupational
Safety
and
Health's
Sentinel
Event
Notification
System
for
Occupational
Risks
(
NIOSH
SENSOR)
performs
standardized
surveillance
in
seven
states
from
1998
through
2002.
States
included
in
this
reporting
system
are
Arizona,
California,
Florida,
Louisiana,
Michigan,
New
York,
Oregon,
Texas,
and
Washington.
Reporting
is
very
uneven
from
state
to
state
because
of
the
varying
cooperation
from
different
sources
of
reporting
(
e.
g.,
workers
compensation,
Poison
Control
Centers,
emergency
departments
and
hospitals,
enforcement
investigations,
private
physicians,
etc.).
Therefore,
these
reports
should
not
be
characterized
as
estimating
the
total
magnitude
of
poisoning.
The
focus
is
on
occupationallyrelated
cases
not
residential
or
other
non­
occupational
exposures.
However,
the
information
collected
on
each
case
is
standardized
and
categorized
according
the
certainty
of
the
information
collected
and
the
severity
of
the
case.

Out
of
5,899
reported
cases
from
1998­
2003,
one
involved
triadimefon.
However,
this
case
was
a
duplicate
of
a
California
case
included
in
the
discussion
above.

Conclusion:
Both
California
and
Poison
Control
Center
data
show
a
clear
pattern
of
irritative,
but
usually
minor
symptoms
from
exposure
to
triadimefon.
Irritation
to
skin,
eyes,
and
respiratory
passage
occur
readily
among
unprotected
handlers
(
applicators
and
mixer/
loaders)
and
among
those
who
have
substantial
contact
with
foliage
such
as
grape
harvesters
and
tenders.
It
was
unclear
whether
triadimefon
might
also
be
a
sensitizer,
contributing
to
allergic­
type
reactions.

Recommendations:
Protection
for
skin
and
eyes
is
recommended
for
handlers
of
triadimefon
and
any
field
workers
that
will
experience
substantial
or
prolonged
contact
with
treated
plants.
Page
103
of
105
11.0
DATA
REQUIREMENTS
A
Developmental
Neurotoxicity
Study
(
DNT)
is
required.

Product
labels
(
EPA
Reg.
Nos.
264­
737
and
432­
1294)
must
be
modified
to
specify
that
aerial
applications
to
orchard
crops
be
made
in
a
minimum
of
10
gal/
A.
Alternatively,
the
registrant
may
submit
crop
field
trial
data
for
orchard
crops
reflecting
application
in
5
gal/
A
using
aerial
equipment.

The
pineapple
field
trial
data
submitted
did
not
indicate
whether
the
dipping
solutions
were
newly
prepared
each
day
or
prepared
once
and
then
reused
for
subsequent
dips.
This
is
a
data
deficiency
and
the
registrant
must
state
if
dipping
solutions
were
prepared
fresh
each
day
or
prepared
once,
and
reused.

To
refine
the
occupational
risk
assessment,
data
on
actual
use
patterns
including
rates,
timing,
and
the
kinds
of
tasks
that
are
required
to
produce
agricultural
commodities
and
other
products
would
better
characterize
triadimefon
risk.
In
addition,
triadimefon­
specific
TTR
or
DFR
data
could
refine
exposure
and
risk
estimates.
Page
104
of
105
APPENDICES
1.0
Toxicology
Data
Requirements
Note
that
use
of
the
new
guideline
numbers
does
not
imply
that
the
new
(
1998)
guideline
protocols
were
used.

Test
Technical
Required
Satisfied
870.1100
Acute
Oral
Toxicity
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
870.1200
Acute
Dermal
Toxicity
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
870.1300
Acute
Inhalation
Toxicity
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
870.2400
Primary
Eye
Irritation
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
870.2500
Primary
Dermal
Irritation
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
870.2600
Dermal
Sensitization
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
yes
yes
yes
yes
yes
yes
yes
yes
yes
yes
yes
yes
870.3100
Oral
Subchronic
(
rodent)
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
870.3150
Oral
Subchronic
(
nonrodent)
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
870.3200
21­
Day
Dermal
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
870.3250
90­
Day
Dermal
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
870.3465
90­
Day
Inhalation
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
yes
yes
no
no
yes
yes
yes
yes
n/
a
no
870.3700a
Developmental
Toxicity
(
rodent)
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
870.3700b
Developmental
Toxicity
(
nonrodent)
.
.
.
.
.
.
.
.
.
.
.
.
870.3800
Reproduction
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
yes
yes
yes
yes
yes
yes
870.4100a
Chronic
Toxicity
(
rodent)
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
870.4100b
Chronic
Toxicity
(
nonrodent)
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
870.4200a
Oncogenicity
(
rat)
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
870.4200b
Oncogenicity
(
mouse)
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
870.4300
Chronic/
Oncogenicity
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
no
yes
no
yes
yes
yes
yes
yes
yes
yes
870.5100
Mutagenicity 
Gene
Mutation
­
bacterial
.
.
.
.
.
.
.
.
870.5300
Mutagenicity 
Gene
Mutation
­
mammalian
.
.
.
.
.
.
870.5xxx
Mutagenicity 
Structural
Chromosomal
Aberrations
870.5xxx
Mutagenicity 
Other
Genotoxic
Effects
.
.
.
.
.
.
.
.
.
.
yes
yes
yes
yes
yes
yes
yes
yes
870.6100a
Acute
Delayed
Neurotox.
(
hen)
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
870.6100b
90­
Day
Neurotoxicity
(
hen)
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
870.6200a
Acute
Neurotox.
Screening
Battery
(
rat)
.
.
.
.
.
.
.
.
.
870.6200b
90
Day
Neuro.
Screening
Battery
(
rat)
.
.
.
.
.
.
.
.
.
.
.
870.6300
Develop.
Neuro
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
no
no
no
no
no
­
­
­
yes
no
870.7485
General
Metabolism
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
870.7600
Dermal
Penetration
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
yes
yes
yes
no
Special
Studies
for
Ocular
Effects
Acute
Oral
(
rat)
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
Subchronic
Oral
(
rat)
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
Six­
month
Oral
(
dog)
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
no
no
no
not
available
not
available
not
available
Page
105
of
105
2.0
PRODUCT
CHEMISTRY
DATA
SUMMARY
OPPTS
Guideline
Number
Requirements:
Triadimefon
[
Technical
Grade
of
Active
Ingredient]

CAS
No.:
43121­
43­
3
PC
Code:
109901
Data
Requirements
Completed.
Y
=
Yes
N
=
No
N/
A
=
Not
Applicable
Results
Master
Record
ID
[
MRID]
Number
830.1550
Product
identity
and
composition
Y
CSF
10/
17/
1996,
CSF
10/
16/
1996
830.1600
Description
of
materials
used
to
produce
the
product
Y
00098119,
423078­
01
830.1620
Description
of
production
process
Y
00098119
,
423078­
01
830.1650
Description
of
formulation
process
Y
00098119,
423078­
01
830.1670
Discussion
of
formation
of
impurities
N
404774­
01
830.1700
Preliminary
analysis
Y
00098120,
441660­
01
830.1750
Certified
limits
N
CSF
10/
17/
1996,
CSF
10/
16/
1996,
441660­
01
830.1800
Enforcement
analytical
method
N
423078­
02
830.1900
Submittal
of
Sample
Y
EPA
Lab
Ft.
Meade,
MD.
Expiration
Date:
05/
2007
830.6302
Color
Y
Colorless
416160­
01
830.6303
Physical
state
Y
Crystalline
solid
416160­
01
830.6304
Odor
Y
Odorless
to
musty
416160­
01
830.6313
Stability
to
normal
and
elevated
temperatures,
metals,
and
metal
ions
Y
Compatible
w/
materials
tested
423078­
03
830.7000
pH
Y
5.5
in
a
1%
suspension
416160­
01
830.7050
UV/
Visible
absorption
N
830.7100
Viscosity
N/
A
416160­
01
830.7200
Melting
point/
melting
range
Y
82.3
º
C
416160­
01
830.7220
Boiling
point/
boiling
range
N/
A
830.7300
Density/
relative
density/
bulk
density
Y
1.23
g/
mL
416160­
01
830.7370
Dissociation
constants
in
water
N/
A
830.7550
Partition
coefficient
(
n­
octanol/
water),
shake
flask
method
Y
1274
log
Po/
w
of
3.11
at
22
º
C
423078­
03
830.7560
Partition
coefficient
(
n­
octanol
/
water)
generator
column
method
See
Guideline
830.7550
830.7570
Partition
coefficient
(
n­
octanol
/
water)
estimation
by
liquid
chromatography
See
Guideline
830.7550
830.7840
Water
solubility:
column
elution
method;
shake
flask
method
Y
64
mg/
L
at
20
º
C
416160­
01
830.7860
Water
solubility,
generator
column
method
See
Guideline
830.7840
830.7950
Vapor
pressure
Y
0.2
mPa
at
20
º
C
423078­
01
0.6
mPa
at
25
º
C
