Document ID: EPA-HQ-OPP-2002-0354-0006
Agency: epa
Document Type: Supporting & Related Material
Title: 
Posted Date: 2006-06-09T04:00Z

Page
1
of
43
UNITED
STATES
ENVIRONMENTAL
PROTECTION
AGENCY
WASHINGTON,
D.
C.
20460
OFFICE
OF
PREVENTION,
PESTICIDES
AND
TOXIC
SUBSTANCES
Date:
March
28,
2006
Memorandum:

SUBJECT:
Secondary
Review
of
"
Biomonitoring
of
Workers
Hand
Thinning
Peaches
Treated
with
Phosmet
Insecticide";
MRID
446823­
01.
PC
Code
059201.
DP
Barcode
D
296574.

FROM:
Matthew
Lloyd,
Industrial
Hygienist
Reregistration
Branch
I
Health
Effects
Division
(
7509C)

THROUGH:
Whang
Phang,
Branch
Senior
Scientist
Reregistration
Branch
I
Health
Effects
Division
(
7509C)

TO:
Diane
Isbell
Reregistration
Review
Branch
2
Special
Review
and
Reregistration
Division
(
7508C)

Attached
is
a
review
of
the
Biomonitoring
of
Workers
Hand
Thinning
Peaches
Treated
with
Phosmet
Insecticide
(
MRID
466823­
01
&
46682302)
study
submitted
by
Gowan
Company
in
support
of
the
re­
registration
of
Phosmet.
This
review
was
completed
by
Versar,
Inc.
under
the
supervision
of
HED.
It
has
undergone
secondary
review
and
reflects
current
Agency
policies.
Page
2
of
43
Executive
Summary:

This
study
was
designed
to
examine
postapplication
exposure
to
workers
hand­
thinning
peach
trees
following
airblast
application
of
Phosmet
insecticide.
The
study
measured
the
change
in
plasma
and
red
blood
cell
cholinesterase
activity
and
to
characterized
urinary
excretion
of
an
absorbed
dose
of
Phosmet.
Urine
was
analyzed
for
the
urinary
metabolites
of
Phosmet
(
N­(
methylsulfinyl)
methyl­
phthalamic
acid
and
N­
(
methylsulfonyl)
methylphthalamic
acid),
the
sulfinyl
and
sulfonyl
metabolites
(
assayed
as
oxidized
sulfonyl).
Potential
Phosmet
equivalents
were
calculated
using
a
molecular
weight
conversion
factor
applied
to
the
metabolite
residue
concentration.
Dislodgeable
foliar
residues
(
DFRs)
of
Phosmet
and
Phosmet
oxon
were
also
measured
for
one
day
pre­
second
application
and
for
the
two
days
following
the
second
application.

A
70%
active
ingredient
(
ai)
wettable
powder
formulation
of
Phosmet
was
applied
by
airblast
sprayer
at
the
maximum
label
rate
of
3
lb
ai/
acre
to
mature
peach
trees
near
Morven,
Georgia
in
the
spring
of
2005.
This
application
was
made
14
days
following
the
first
seasonal
application
of
Phosmet
to
that
peach
orchard.
A
crew
of
16
workers
(
14
male
and
2
female)
re­
entered
the
field
two
days
after
the
second
application,
in
order
to
hand
thin
the
trees.
Blood
and
24­
hour
urine
samples
were
collected
from
the
workers
on
four
pre­
exposure
days,
four
post­
exposure
days,
and
on
the
day
of
exposure.

The
24­
hour
urine
collections
were
assayed
for
creatine
and
sulfonyl
concentration.
To
account
for
incomplete
sample
collection,
the
Study
Report
compared
measured
creatinine
to
expected
creatinine
for
each
individual
at
each
sampling
event.
Based
on
this
estimate
of
expected
creatinine,
an
adjustment
factor
was
applied
to
the
sulfonyl
concentration
in
each
urine
collection.
The
Study
Author
did
not
factor
any
pharmacokinetic
data
into
the
estimation
of
phosmet
equivalent
dose.
One
factor
typically
considered
in
the
estimate
of
dose
is
the
percentage
of
active
ingredient
converted
to
urinary
metabolite
and
subsequently
excreted
in
the
urine.
Another
factor
to
be
considered
is
the
percentage
of
metabolite
expected
to
be
excreted
during
the
sampling
time
period.
The
Study
Report
protocol
states
that
the
sulfinyl
and
sulfonyl
metabolites
of
phosmet
account
for
approximately
50­
60%
of
the
administered
radioactivity
in
urine
in
a
rat
oral
metabolism
study.
HED
made
corrections
for
the
percentage
of
active
ingredient
converted
to
urinary
metabolite
and
excreted
in
urine
(
95%)
and
a
correction
(
55%)
to
account
for
the
percentage
of
administered
radioactivity
in
urine
in
a
rat
oral
metabolism
study
(
MRID
404253­
01)
in
their
estimate
of
dose.

Both
plasma
and
red
blood
cell
cholinesterase
activity
was
monitored
throughout
the
conduct
of
the
study,
as
well
as
on
several
pre­
exposure
days.
The
Study
Author
reported
no
remarkable
findings
and
no
exposure­
related
depression
of
either
plasma
or
red
blood
cell
cholinesterase
activity
for
the
designated
exposure
day.

Dislodgeable
foliar
residue
(
DFR)
was
measured
on
the
day
before
the
second
application,
the
day
of
the
second
application
(
2
days
prior
to
reentry
activity)
and
for
the
following
5
days
(
i.
e.,
7
monitored
days).
The
Study
Author
concluded
that
the
continuing
hard
rain
at
the
end
of
the
exposure
day
had
affected
the
dissipation
kinetics
Page
3
of
43
and
reported
that
a
meaningful
dissipation
curve
could
not
be
developed.
The
residues
on
days
one
and
two
after
the
phosmet
application
demonstrate
residue
levels
consistent
with
previous
Phosmet
DFR
studies,
though
after
the
rain
event
the
phosmet
residues
drop
off
significantly.
The
Phosmet
oxon
was
also
measured
in
the
DFR
and
was
found
to
be
a
tiny
fraction
of
the
parent.

There
were
a
number
of
issues
that
introduced
uncertainty
into
the
study,
including
the
following:

 
Stormy
weather
changed
the
intended
activity
day
from
day
3
postapplication
to
day
2
postapplication
With
a
forecast
predicting
rain,
the
study
authors
moved
up
the
worker
postapplication
activity
day
from
day
3
postapplication
to
day
2
postapplication.
The
rain
began
to
fall
in
the
afternoon
of
day
2
postapplication
while
the
workers
were
still
conducting
thinning.

 
Shortened
work
day
due
to
rain
event
On
the
reentry
day,
an
afternoon
thunderstorm
forced
the
subjects
to
take
cover
for
half
an
hour.
They
returned
to
work,
although
the
rain
intensity
steadily
increased
and
the
work
day
was
called
off.
Total
working
time
was
roughly
6
hours
before
the
rain
and
half
an
hour
in
the
rain
for
a
6.5
hour
workday.

 
DFR
analysis
compromised
by
the
rain
event
The
Study
Author
concluded
that
the
continuing
hard
rain
at
the
end
of
the
exposure
day
had
affected
the
dissipation
kinetics
and
reported
that
a
meaningful
dissipation
curve
could
not
be
developed.
The
residues
declined
from
4.06
ug/
cm2
on
day
2
(
the
day
the
rain
started)
to
0.99
ug/
cm2
on
day
4
(
the
day
the
rain
ended).
The
Study
Report
did
not
detail
what
time
of
the
day
the
DFR
samples
were
collected,
further
complicating
interpretation
of
the
DFR
results.

 
Poor
participant
compliance
with
urine
collection
The
Study
Report
details
compliance
issues
with
regard
to
urine
sample
collection
procedures.
Many
of
the
24
hour
urine
collections
demonstrate
total
volumes
substantially
below
what
is
expected
for
normal,
healthy
adults.
The
volume
of
urine
produced
by
a
normal
adult
over
a
24
hour
period
typically
ranges
between
800
and
1800
mL
(
Tietz,
1970).
Sample
volumes
obtained
from
the
16
workers
against
this
standard
demonstrate
that
28
of
123
urine
collections
were
below
what
normally
would
be
expected.
The
study
authors
cited
an
instance
of
a
field
observer
witnessing
a
study
participant
urinating
on
the
ground,
instead
of
in
the
sample
collection
bottles.
Page
4
of
43
 
Unknown
effect
of
rain
on
thinning
activity
day
The
effect
of
the
rain
event
on
the
phosmet
exposure
estimate
is
unknown.
The
rainfall
could
have
washed
the
transferable
residue
from
the
leaves,
and/
or
washed
residue
from
the
workers'
skin
and
clothing.
It
was
also
possible
that
the
rain
would
solubilize
the
DFRs
making
them
more
readily
available
for
transfer,
or
the
water
mass
could
have
pushed
residues
through
the
clothing
to
skin
increasing
dermal
exposure,
or
that
the
damp
clothing
could
hydrate
the
skin,
possibly
enhancing
dermal
absorption.

 
Inconsistent
worker
apparel
The
study
authors
requested
workers
to
have
socks,
shoes,
long
pants
and
a
long
sleeve
shirt.
No
one
was
turned
away
from
wearing
more
clothing
than
initially
requested.
The
day
warmed
up
quickly
and
a
number
of
workers
shed
some
clothing
as
the
temperature
increased.
They
then
added
it
back
on
at
some
point
during
the
rain
event.
Exposure
is
difficult
to
characterize
accurately
in
these
circumstances.
A
few
of
the
workers
wore
jackets
for
part
of
the
workday,
some
of
the
workers
wore
gloves,
some
wore
hats,
some
workers
wore
short­
sleeved
shirts
and
others
wore
long­
sleeved
shirts.
Seven
of
sixteen
had
more
clothing
than
study
authors
requested
for
at
least
2
hours.
That
includes
clothing
items
like
caps,
hats,
gloves,
and
jackets.

 
Analytical
lab
utilized
for
cholinesterase
activity
does
not
have
data
to
support
whether
storage
length
of
samples
(
1
month)
frozen
blood
samples
would
affect
storage
stability
The
study
report
does
not
mention
storage
temperatures
for
the
blood
samples.
There
is
a
possibility
that
the
interaction
of
the
phosmet
and
the
enyzme
may
be
altered
during
storage.
Page
5
of
43
DFR
vs.
time
for
Georgia
Biomonitoring
Study
0
1
2
3
4
5
6
7
DAY
AFTER
TREATMENT
0
1
2
3
4
5
DCNA
Residue
UG/

CM2
R­
square
=
0.924
#
pts
=
6
y
=
5.77
+
­
0.96x
PEACH
DFR
DATA
FOR
THE
GEORGIA
TEST
SITE
Page
6
of
43
References:

Tietz,
Norbert
W.
ed.
(
1970).
Fundamentals
of
Clinical
Chemistry,
Philadelphia,
PA:
W.
B.
Saunders
Company.
ISBN
0­
7216­
8865­
9.
Page
7
of
43
Reviewer:
Teri
Schaeffer/
Traci
Brody/
Susan
Anderson
Date:
March
10,
2006
STUDY
TYPE:
Post­
application
biological
monitoring
study
TEST
MATERIAL:
Phosmet
SYNONYMS:
Imidan
®
O,
O­
dimethyl
S­
phthalimidomethyl
phosphorodithioate
(
IUPAC)

CITATION:
Study
Author:
Douglas
G.
Baugher,
Ph.
D.
Title:
Biomonitoring
of
Workers
Hand­
thinning
Peaches
Treated
with
Phosmet
Insecticide.
Report
Date:
October
31,
2005
Analytical
Laboratories:
PTRL
West,
Inc.
625­
B
Alfred
Nobel
Drive
Hercules,
CA
94547
Identifying
Codes:
MRID:
46682301
Report
No.:
0512
Study
Number:
EXP­
49404
SPONSOR:
Gowan
Company
370
South
Main
Street
Yuma,
AZ
85364
EXECUTIVE
SUMMARY:

This
study
was
designed
to
examine
postapplication
exposure
to
16
workers
hand­
thinning
peach
trees
following
airblast
application
of
phosmet
insecticide.
The
study
proposed
to
measure
the
change
in
plasma
and
red
blood
cell
cholinesterase
activity
and
to
characterize
urinary
excretion
of
an
absorbed
dose
of
phosmet
following
one
day
of
hand­
thinning
peach
trees
at
the
reentry
interval
(
REI)
of
two
days
postapplication.
Urine
was
analyzed
for
the
urinary
metabolites
of
phosmet
(
N­(
methylsulfinyl)
methyl­
phthalamic
acid,
and
N­(
methylsulfonyl)
methylphthalamic
acid),
the
sulfinyl
(
SI)
and
sulfonyl
(
SO)
metabolites
(
assayed
as
oxidized
sulfonyl).
Potential
phosmet
equivalents
were
calculated
using
a
molecular
weight
conversion
factor
applied
to
the
metabolite
residue
concentration.
A
small
sampling
of
dislodgeable
foliar
residues
(
DFRs)
of
phosmet
and
phosmet
oxon
were
also
presented.

A
70%
active
ingredient
(
ai)
wettable
powder
formulation
of
phosmet
was
applied
by
airblast
sprayer
at
a
use
rate
of
3
lb
ai/
acre
to
mature
peach
trees
near
Morven,
Georgia
in
the
spring
of
2005.
The
application
rate
was
verified
by
application
pass
times
rather
than
tank
mix
analysis.
The
application
was
made
14
days
following
a
first
seasonal
application
event.
A
crew
of
16
workers
(
male
and
female)
re­
entered
the
field
two
days
after
the
second
application,
in
order
to
hand
thin
the
trees.
Blood
and
24­
hour
urine
samples
were
collected
from
the
workers
on
four
pre­
exposure
days,
four
post­
exposure
days,
and
on
the
day
of
exposure.

The
Study
Authors
estimated
phosmet­
equivalent
dose
by
measurement
of
the
urinary
sulfonyl
(
SO)
and
sulfinyl
(
SI)
metabolites
of
phosmet
in
24
hour
urine
samples
collected
for
five
consecutive
days
beginning
on
the
morning
of
postapplication
reentry.
Over
half
of
the
pre­
exposure
samples
showed
no
detectable
level
of
SO
residue
in
the
urine.
Total
estimated
phosmet
equivalents
ranged
from
1,031
µ
g/
day
to
9,488
µ
g/
day.
These
reported
phosmet­
equivalents
do
not,
however,
take
into
consideration
the
pharmacokinetics
of
phosmet
metabolism.
The
highest
daily
concentrations
was
generally
found
on
the
first
exposure
day
(
ED
0),
although
four
of
the
sixteen
workers
Page
8
of
43
demonstrated
the
highest
urine
levels
on
the
second
exposure
day
(
ED
+
1).
Levels
steadily
decreased
during
the
monitoring
period;
however,
the
levels
did
not
reduce
to
pre­
exposure
levels
by
the
end
of
the
sample
collection
period.

Both
plasma
and
red
blood
cell
cholinesterase
activity
was
monitored
throughout
the
conduct
of
the
study,
as
well
as
on
several
pre­
exposure
days.
The
Study
Author
reported
no
remarkable
findings
and
no
exposure­
related
depression
of
either
plasma
or
red
blood
cell
cholinesterase
activity.

Dislodgeable
foliar
residue
(
DFR)
was
examined
on
the
day
before
the
second
application,
the
day
of
the
second
application
(
2
days
prior
to
reentry
activity)
and
for
the
following
5
days
(
i.
e.,
7
monitored
days).
The
Study
Author
concluded
that
the
continuing
hard
rain
at
the
end
of
the
exposure
day
had
affected
the
dissipation
kinetics
and
reported
that
a
meaningful
dissipation
curve
could
not
be
developed.
The
residues
on
the
day
of
second
application
and
the
following
day
demonstrated
residues
comparable
to
previous
phosmet
DFR
studies.
The
phosmet
DFR
on
days
1
and
2
postapplication
averaged
5.9
ug/
cm2
and
5.0
ug/
cm2,
respectively.
Phosmet
oxon
DFR
on
days
1
and
2
postapplication
averaged
0.012
ug/
cm2
and
0.010
ug/
cm2,
respectively.

Major
issues
of
concern
in
evaluation
of
the
study
include:

 
Other
than
a
molecular
weight
factor
to
account
for
the
difference
in
molecular
weight
between
the
urinary
metabolite
sulfonyl,
and
the
active
ingredient
phosmet,
the
Study
Author
did
not
factor
any
pharmacokinetic
data
into
the
estimation
of
phosmet
equivalent
dose.
One
factor
typically
considered
in
the
estimate
of
dose
is
the
percentage
of
active
ingredient
converted
to
urinary
metabolite
and
subsequently
excreted
in
the
urine.
Another
factor
to
be
considered
is
the
percentage
of
metabolite
expected
to
be
excreted
during
the
sampling
time
period.
The
Study
Report
protocol
states
that
the
sulfinyl
and
sulfonyl
metabolites
of
phosmet
account
for
approximately
50­
60%
of
the
administered
radioactivity
in
urine
in
a
rat
oral
metabolism
study.
The
Authors
did
not
take
this
into
consideration
in
their
estimate
of
dose.

 
Many
of
the
24
hour
urine
collections
demonstrate
total
volumes
substantially
below
what
is
expected
for
normal,
healthy
adults.
The
volume
of
urine
produced
by
a
normal
adult
over
a
24
hour
period
typically
ranges
between
800
and
1800
mL
(
Tietz,
1970).
Sample
volumes
obtained
from
the
16
workers
against
this
standard
demonstrate
that
28
of
123
urine
collections
were
below
what
normally
would
be
expected.

 
The
Study
Authors
attempted
to
correct
for
incomplete
urine
collection.
They
adjusted
sulfonyl
concentration
in
the
urine
samples
using
a
technique
which
compared
measured
creatinine
to
expected
creatinine
for
each
individual
at
each
sampling
event
(
Mage
et
al.,
2004).
Based
on
this
estimate
of
expected
creatinine,
an
adjustment
factor
was
applied
to
the
sulfonyl
concentration
in
each
urine
collection.
Use
of
this
correction
strategy
resulted
in
adjustment
factors
ranging
from
0.64
to
4.38.
Use
of
factors
of
this
magnitude
indicates
that
in
some
instances,
urine
volume
was
as
low
as
25%
of
the
expected
volume.

 
The
study
Authors
also
applied
the
adjustment
factor
to
those
samples
where
the
actual
creatinine
level
was
higher
than
the
expected
creatinine
level
(
e.
g.,
adjustment
factor
<
1.0).
This
had
the
effect
of
reducing
the
sulfonyl/
sulfinyl
that
was
actually
excreted
by
those
individuals.

 
The
DFR
analysis
was
most
likely
compromised
by
an
exposure
day
rainfall
event.
The
Study
Report
states
that
the
"
continued
hard
rain
at
the
end
of
the
exposure
day
had
affected
the
dissipation
kinetics
and
that
a
meaningful
dissipation
curve
could
not
be
developed."
The
study
authors
report
that
residue
levels
on
the
first
and
second
day
after
the
second
application
(
approximately
6
and
5
ug/
cm2,
respectively)
were
consistent
with
expected
DFR
values.
When
comparing
the
DFR
results
with
previously
conducted
phosmet
dissipation
regression
curves,
it
appears
that
residues
levels
determined
after
the
rain
event
demonstrate
significantly
lower
levels
than
those
expected.

 
In
the
afternoon
of
the
reentry
day,
postapplication
activities
were
cut
short
due
to
heavy
rain.
The
affect
of
this
event
on
the
phosmet
exposure
estimate
is
unknown.
It
is
possible;
however,
that
meaningful
exposure
Page
9
of
43
was
affected.
The
rainfall
could
have
washed
the
transferable
residue
from
the
leaves,
and/
or
washed
residue
from
the
workers'
skin
and
clothing.
Or
it
is
possible
that
the
rain
would
solubilize
the
DFRs
making
them
more
readily
available
for
transfer,
or
the
water
mass
could
have
pushed
residues
through
the
clothing
to
skin
increasing
dermal
exposure,
or
the
damp
clothing
could
hydrate
the
skin,
possibly
enhancing
dermal
absorption.

 
Urinary
field
fortification
levels
were
inconsistent,
with
seven
samples,
or
25%,
demonstrating
recovery
values
less
than
50%.
The
Study
Author
deleted
these
values
from
the
calculation
of
average
recovery,
reporting
that
the
values
must
have
been
misfortified.
If
these
fortification
values
were
included
in
the
calculations,
overall
recovery
would
be
84%,
necessitating
the
use
of
a
correction
factor.

 
The
clothing
worn
by
the
workers
was
inconsistent.
It
is
difficult
to
accurately
characterize
exposure
in
these
circumstances.
Table
1
outlines
the
clothing
worn
by
the
individual
workers.
A
few
of
the
workers
wore
jackets
for
part
of
the
workday,
some
of
the
workers
wore
gloves,
some
wore
hats,
some
workers
wore
shortsleeved
shirts
and
others
wore
long­
sleeved
shirts.

 
Several
of
the
urine
samples
demonstrate
incomplete
oxidation
of
sulfinyl
metabolite
to
the
quantified
metabolite,
sulfonyl.
The
phosmet
equivalent
levels
are
based
on
measurement
of
sulfonyl
only.
The
Study
Authors
did
not
adjust
the
estimate
of
phosmet
concentration
to
account
for
this.

 
EPA
Reg
No.
10163­
169
specifies
a
maximum
use
rate
of
4.25
lbs.
ai/
A.
The
test
substance
was
applied
to
the
peach
trees
at
a
rate
of
3
lbs.
ai/
A.

 
Postapplication
activities
were
cut
short
(
i.
e.,
the
workers
worked
6.5
hours
on
the
day
of
exposure)
due
to
the
rainfall.

 
Creatinine
levels
were
determined;
however,
it
was
not
reported
if
the
specific
gravity
of
the
urine
was
analyzed.

 
It
is
not
well
established
that
washed
red
cells
can
be
frozen
for
a
period
of
approximately
one
month
and
then
assayed
for
RChe
activity,
as
was
the
case
in
this
Study.
The
laboratory
utilized
by
the
Study
Author
reports
that
their
RChe
method
was
validated
using
fresh
specimens
(
within
48
hours
of
collection)
for
estimation
of
RChe
activity.
The
analytical
lab
utilized
for
cholinesterase
testing
does
not
have
data
to
support
whether
or
not
frozen
storage
would
affect
stability.

 
This
study
was
conducted
at
only
one
test
site,
a
peach
orchard
in
Morven,
Georgia.
Therefore,
DFR
data
was
not
collected
from
at
least
three
geographically
distinct
locations
for
each
formulation
and
crop
type
as
specified
in
the
guidelines.
Page
10
of
43
COMPLIANCE:
Signed
and
dated
GLP,
Data
Confidentiality
statements,
and
Quality
Assurance
statements
were
provided
in
the
Study
Report.
The
Study
Report
states
that
it
meets
FIFRA
Good
Laboratory
Practices
40
CFR
part
160
with
the
following
exceptions:
(
1)
the
clinical
facilities
did
not
operate
under
the
GLP,
but
were
licensed
and
accredited;
(
2)
no
data
evaluations,
interpretations,
or
reports
were
generated
by
the
labs;
(
3)
tank­
mix
samples
were
not
collected
during
the
application
of
the
test
product;
(
4)
one
set
of
the
field
fortified
urine
samples
was
placed
into
a
freezer
rather
than
into
a
cooler;
(
5)
LabCorp
was
not
identified
in
the
study
protocol
as
the
facility
used
to
assay
blood
samples;
and
(
6)
the
Study
Director
selected
the
samples
for
analysis
and
inclusion
in
reporting
based
on
relevance
to
the
study
objectives
without
protocol
amendment.
The
statement
noted
that
none
of
these
exceptions
negatively
impacted
the
integrity
of
the
study.

GUIDELINE
OR
PROTOCOL
FOLLOWED:
The
Protocol
was
approved
by
the
Western
Institutional
Review
Board
(
WIRB)
and
provided
in
the
Study
Report.
The
Study
Report
states
that
the
exposure
data
requirements
were
from
U.
S.
EPA
OPPTS
Harmonized
Test
Guidelines,
Series
875
Occupational
and
Residential
Exposure,
Group
B
875.2600,
Biological
Monitoring.
The
DFR
data
requirements
were
from
U.
S.
EPA
OPPTS
Harmonized
Test
Guidelines,
Series
875,
Part
B:
Dislodgeable
Foliar
Residue
Dissipation:
Agricultural,
Guideline
875.2100.

I.
MATERIALS
AND
METHODS
A.
MATERIALS
1.
Test
Material:

Formulation:
Imidan
®
70
W
­
water
soluble
packets
containing
70%
phosmet
as
the
active
ingredient.
Lot/
Batch
#
formulation:
Imidan
®
:
316­
129A/
30AK4163
Phosmet
oxon:
1232W­
001B
Sulfinyl
urinary
metabolite:
13449­
5
Sulfonyl
urinary
metabolite:
13449­
8
Purity:
Imidan
®
:
The
purity
of
the
batch
was
verified
at
98%
with
an
expiration
date
of
February,
2007.
Phosmet
oxon:
The
purity
of
the
batch
was
verified
at
99.7%
with
an
expiration
date
of
November
3,
2006.
Sulfinyl
urinary
metabolite:
The
purity
of
the
batch
was
verified
at
93.86%
with
an
expiration
date
of
June
22,
2006.
Sulfonyl
urinary
metabolite:
The
purity
of
the
batch
was
verified
at
97.01%
with
an
expiration
date
of
June
22,
2006.
CAS
#(
s):
Phosmet:
732­
11­
6
Other
Relevant
Information:
Imidan
®
70
W
­
EPA
Reg.
No.
10163­
169
2.
Relevance
of
Test
Material
to
Proposed
Formulation(
s):
A
label
was
not
provided
with
the
Study
Report;
however,
Versar
was
able
to
obtain
a
label
from
the
OPP
Pesticide
Products
Database
using
the
EPA
registration
number.
The
wettable
powder
formulation
sent
to
the
field
sites
was
labeled
as
Imidan
 
70
W,
which
is
the
same
product
name
that
appears
on
the
label.

3.
Packaging:
The
product
was
packaged
in
water
soluble
bags
in
40
lb
cardboard
cartons.

B.
STUDY
DESIGN
Page
11
of
43
There
were
5
amendments
to
the
protocol.
These
amendments
included:

(
1)
A
local
laboratory
could
not
be
found
to
analyze
the
blood
samples
the
same
day
of
sample
collection
therefore
additional
sample
collection
procedures
were
instituted
to
account
for
proper
sample
storage
and
shipping.
Additionally,
clarifications
were
made
to
the
procedure
for
worker
illness,
injury
or
manifestation
of
illness
and
acquiring
medical
attention.
Changes
were
made
with
the
informed
consent,
changing
the
criteria
for
determining
when
a
worker
should
be
transported
to
a
hospital
emergency
room
and
subsequent
allowable
return
to
work.

(
2)
Minor
changes
were
made
concerning
the
application
rate
to
accommodate
water
soluble
bag
packaging.
Application
of
test
substance
timing
was
changed
from
an
8AM
deadline
to
an
11AM
deadline.
Leaf
punch
size
was
clarified
(
diameter
size
of
the
leaf
punch
discs
was
2.5
cm).
The
addition
of
Day
7
sampling
interval
for
DFR
sampling
was
included,
and
additional
field
fortification
levels
were
included.
.
Urine
aliquot
preparation
was
changed
from
the
field
site
to
the
analytical
lab
and
additional
urine
control
sampling
fortifications
were
included.

(
3)
A
plan
was
instituted
for
possible
reentry
on
day
2
postapplication
to
allow
flexibility
in
accommodating
rain
or
forecast
rain.
This
amendment
was
instituted.
The
currently
registered
and
marketed
label
allows
reentry
at
one
day
postapplication.

(
4)
The
protocol
called
for
estimating
the
urine
volumes
when
collected
and
this
was
changed
to
making
exact
urine
volume
measurements
at
the
analytical
laboratory.
Changed
the
DFR
sampling
protocol
from
ARTF
SOPs
to
SEAgR
SOPs.
Changing
the
collection
of
DFR
field
fortification
samples
to
only
days
the
treated
plot
is
sampled
after
the
second
application.
Changing
the
number
of
non­
treated
DFR
samples
collected
from
5
to
3.
Starting
on
Day
4,
the
urine
samples
were
jointly
spiked
with
sulfonyl
and
sulfinyl
metabolites.
The
pH
of
the
spray
solution
was
not
adjusted
to
less
than
or
equal
to
7.
Another
orchard
of
peaches
was
treated
nearby
with
phosmet
in
case
additional
trees
were
needed
to
keep
the
thinners
busy.
Ten,
rather
than
five
DFR
samples
were
collected
from
the
treated
plot
on
the
day
of
reenty.

(
5)
This
amendment
provided
additional
information
about
the
laboratory
used
for
creatinine
analysis.

The
protocol
was
amended
to
include
a
storage
stability
study
of
phosmet
urinary
metabolites
in
urine
for
storage
intervals
of
one
week
and
two
weeks
at
freezer
temperature.
The
protocol
was
also
amended
to
change
the
urine
storage
stability
fortification
set
such
that
each
urine
storage
stability
sample
would
be
fortified
with
both
phosmet
urinary
metabolites
instead
of
fortifying
each
metabolite
to
separate
urine
samples.

A
list
of
protocol
deviations
include:
(
1)
the
sodium
sulfate
was
not
heated
in
a
muffle
furnace
at
600
º
C
for
2
hours
prior
to
use,
(
2)
50
mL
of
DFR
solution
was
fortified
when
preparing
fortified
control
samples
rather
than
the
specified
200
mL,
(
3)
125
mL
separatory
funnels
were
used
for
partitioning
rather
than
250
mL
separatory
funnels,
(
4)
a
15
meter
DB­
5MS
column
was
used
not
a
10
or
20
meter
column.
The
Study
Author
states
that
these
deviations
would
have
no
impact
on
the
study.

1.
Test
Site:
The
test
site
was
a
peach
orchard
located
in
Morven,
near
Valdosta,
Georgia.
The
orchard
contained
approximately
17.5
acres
with
45
rows
of
peach
trees.
Each
tree
was
planted
16
ft
apart
and
each
row
was
spaced
19
ft
apart.
The
variety
of
peach
was
Florida
Crest
and
the
trees
were
4
years
old.
The
mature
trees
(
approximately
7
ft
tall)
had
a
very
good
crop
that
required
thinning.
Many
of
the
leaves
were
>
2.5
cm
in
width.
The
entire
orchard
was
used
as
the
test
plot
and
according
to
the
Study
Report
subplots
were
not
necessary.

The
orchard
received
no
applications
of
cholinesterase
inhibiting
pesticides
during
the
field
phase
of
the
study
other
than
the
monitored
phosmet
applications.
Typical
cultural
practices
were
employed
at
the
site.

2.
Meteorology:
Page
12
of
43
Meteorological
conditions
were
recorded
during
the
applications.
Temperature
and
rainfall
data
were
collected
on­
site
with
automated
Hobo
monitors.
According
to
the
Study
Report,
the
weather
was
favourable
for
both
application
dates.
This
information
is
provided
in
Table
1.
The
Study
Report
also
noted
that
there
was
no
precipitation
or
overhead
irrigation
during
the
period
between
the
second
application
and
the
day
of
monitoring.
Temperatures
on
the
day
between
application
and
monitoring
ranged
from
48
to
82oF.

On
the
day
of
the
reentry
thinning
tasks,
the
weather
was
mixed
clouds
and
sun,
with
temperatures
rising
from
69
to
83oF
with
the
relative
humidity
ranging
from
67%
to
90%.
The
relative
humidity
data
was
obtained
from
the
Dixie,
GA
site
of
the
Georgia
Automated
Weather
Network
located
approximately
13
miles
from
the
test
site.
In
the
afternoon
of
the
reentry
day,
postapplication
activities
were
cut
short
due
to
a
significant
rain
event.
Workers
completed
their
morning
work
at
noon
and
then
took
a
break
for
lunch.
They
returned
to
the
fields
around
1:
20
PM.
Two
hours
later,
a
thunderstorm
forced
the
subjects
to
take
cover
in
vehicles
for
about
25
minutes.
They
then
reentered
the
fields
even
though
it
was
raining
lightly.
The
rain
intensity
increased,
and
after
less
than
25
minutes,
the
subjects
had
to
cease
work,
leave
the
orchard,
and
return
to
the
staging
area.
On­
site
rainfall
data
collected
with
automated
Hobo
monitors
reported
0.32
inches
of
rainfall
on
31
March,
the
day
of
reentry.
During
the
next
two
days,
2.09
and
0.02
inches
of
rain
fell.
Table
2
provides
rainfall
data
for
the
duration
of
the
study.

Table
1.
Meteorological
Conditions
During
Applications
Parameter
First
Application
(
3/
15/
05)
Second
Application
(
3/
29/
05)

Air
Temperature
(
oF)
52
to
73
50
to
77
Wind
Speed
(
mph)
0
to
6
2
to
11
Percent
Cloud
Cover
Overcast
Clear
skies
Table
2.
Rainfall
Events
for
Duration
of
Study
Date
Activity
Rainfall
(
inches)

March
15,
2005
First
Application
0.38
March
16,
2005
2.23
March
17,
2005
0.05
March
22,
2005
1.40
March
23,
2005
0.03
March
25,
2005
0.70
March
26,
2005
1.48
March
27,
2005
0.26
March
28,
2005
0.01
March
29,
2005
Second
Application
Pre­
App
DFR
Sampling
0
March
30,
2005
1DAT
DFR
Sampling
0
March
31,
2005
Reentry
Exposure
Monitoring
2DAT
DFR
Sampling
0.32
April
1,
2005
3DAT
DFR
Sampling
2.09
April
2,
2005
4DAT
DFR
Sampling
0.02
April
3,
2005
5DAT
DFR
Sampling
0
April
4,
2005
6DAT
DFR
Sampling
0
3.
Number
and
type
of
workers:
Page
13
of
43
Sixteen
workers
made
up
of
both
men
and
women
were
monitored
for
this
study.
The
work
crew
was
made
up
of
14
annual
temporary
immigrants
from
Mexico
and
two
permanent
residents
employed
as
farm
workers.
The
Study
Report
stated
that
the
workers
were
not
exposed
to
phosmet
or
any
other
cholinesterase
inhibiting
pesticides
on
workdays
before
and
after
the
2
day
REI.
Each
worker
was
identified
by
a
letter
of
the
alphabet
(
A
through
R).
The
workers
ranged
in
age
from
17
years
to
60
years.
The
weight
of
the
workers
ranged
from
47.7
kg
to
117.7
kg.
The
workers'
years
of
experience
ranged
from
<
1
year
to
8
years.
All
of
the
workers
had
thinning
experience,
except
for
M,
N,
R,
and
S,
who
were
trained
the
day
before
the
reentry
event.
All
of
the
workers
were
provided
with
an
informed
consent
form
to
read
and
sign
prior
to
the
start
of
the
study.

4.
Exposure
Replicates:
At
the
beginning
of
the
study
there
were
16
workers
selected
to
participate
and
each
worker
was
identified
by
a
letter
of
the
alphabet
(
A
through
R).
Workers
H
and
K
dropped
out
of
the
study
before
any
samples
were
collected.
Each
worker
was
monitored
for
9
days.
The
one
day
of
exposure
occurred
on
the
second
day
after
the
second
seasonal
application.
Peach
tree
thinning
postapplication
activities
took
place
2
days
after
the
airblast
application
of
3.0
lb
ai/
A
of
phosmet
to
the
test
site.
Each
worker
was
assigned
to
his/
her
own
row
for
thinning.
A
record
of
trees
thinned
and
any
other
noteworthy
events
was
recorded.
The
morning
shift
began
in
the
orchard
a
few
minutes
after
8:
00
AM
and
productivity
was
considered
normal.
The
workers
left
the
orchard
at
noon
for
lunch.
The
workers
returned
to
the
orchard
by
1:
20
PM.
The
afternoon
shift
was
unremarkable
until
a
thunderstorm
forced
the
workers
to
take
cover
in
vehicles
from
3:
25
PM
to
3:
40
PM,
at
which
time
they
re­
entered
the
orchard
to
continue
with
their
thinning
tasks.
It
was
raining
lightly,
but
the
crew
foreman
indicated
that
they
would
normally
work
in
this
weather.
The
rain
intensity
increased,
and
by
4:
05
PM
the
workers
left
the
orchard
for
the
day.
Total
working
time
was
approximately
6
hours
before
the
rainfall
and
25
minutes
in
the
rain.
The
Study
Report
states
that
productivity
for
this
sampling
event
was
"
considered
typical."
The
workers
were
issued
clean,
dry
clothing
when
they
returned
to
the
staging
area.
Some
of
the
workers
changed
clothing
immediately,
and
others
waited
until
reaching
their
living
quarters
before
changing.
Pages
103
through
115,
in
the
Study
Report,
provide
observations
of
the
workers
recorded
during
the
study.

5.
Protective
clothing:
The
Study
Report
states
that
the
workers
wore
their
own
clothing.
Table
3
outlines
the
clothing
worn
by
the
individual
workers.
A
few
of
the
workers
wore
jackets
for
part
of
the
workday,
some
of
the
workers
wore
gloves,
some
wore
hats,
some
workers
wore
short­
sleeved
shirts
and
others
wore
long­
sleeved
shirts.

Table
3.
Test
Subjects
and
Clothing
Worn
During
Exposure
Event
Replicate
Clothing
Notes
A
Denim
jacket,
long
sleeves,
brimmed
hat,
leather
shoes,
socks,
denim
pants
Jacket
removed
after
lunch
B
Long­
sleeves,
cap,
socks,
leather
shoes,
twill
pants
C
Long­
sleeves
over
short­
sleeves,
cap,
socks,
soft
shoes,
corduroy
pants
Sleeves
rolled
up
after
25
minutes
working,
jacket
after
rain
started
D
Coat,
long­
sleeves
shirt,
socks,
soft
shoes,
khaki
pants
Removed
jacket
and
tied
around
waist,
and
went
to
short­
sleeves
after
10
minutes
working,
jacket
totally
removed
after
2
hours
working
and
put
on
again
after
rain
E
Long­
sleeves,
socks,
soft
shoes,
jeans
F
2
short­
sleeved
shirts,
cap,
socks,
soft
shoes,
jeans
G
Long­
sleeved
shirt
over
other
shirt,
socks,
leather
shoes,
linen
pants
Removed
long­
sleeved
shirt
and
tied
around
waist
after
lunch,
put
jacket
back
on
after
rains
started
I
Short­
sleeves
over
knit
shirt,
cap,
jeans,
leather
shoes,
Page
14
of
43
Replicate
Clothing
Notes
J
Jacket,
jeans,
long­
sleeved
shirt,
socks,
tennis
shoes,
cap,
Jacket
removed
and
tied
around
waist
,
longsleeves
pushed
up
(
after
2
hours
work)

L
Long­
sleeved
shirt,
jeans,
cap,
socks,
tennis
shoes,
one
glove
(
jersey
weave),
bandana
at
neck
Took
off
glove
at
some
point
in
the
afternoon
M
Long­
sleeved
shirt,
jeans,
cap,
tennis
shoes
and
tshirt
N
Short­
sleeved
t­
shirt,
cap,
jeans,
socks
hiking
boots
O
Short­
sleeved
collared
shirt,
pants,
cap,
socks,
tennis
shoes
P
Short­
sleeved
t­
shirt,
cropped
pants
above
ankle,
tennis
shoes,
cloth
gloves
Q
Long­
sleeved
shirt,
jeans,
socks,
work
boots,
cap
R
Long­
sleeved
collared
shirt,
jeans,
boots,
socks,
cap
Long­
sleeves
cuffed
up
or
rolled
back
and
forearms
exposed
6.
Application
Method
and
Rate:

Application
rate(
s):
Two
foliar
applications
were
made
at
3.0
lb
ai/
A
on
March
15,
and
March
29
of
2005.
According
to
EPA
Reg
No.
10163­
169,
the
maximum
application
rate
is
4.25
lb
ai/
A
per
application.

Antifoaming
agents
were
used
at
a
rate
of
2
to
3
fluid
ounces
of
antifoaming
agent
per
tank
load.
During
the
second
application,
the
pH
was
adjusted
from
8.0
to
6.0
with
Quest
at
a
rate
of
0.5
pints
per
100
gallons.

Application
Equipment:
The
applications
were
made
according
to
usual
agricultural
practice,
using
the
orchard
owner's
equipment
driven
by
an
experienced
employee.
The
applications
were
made
with
a
new
Durand
Wayland
AF505
airblast
sprayer
driven
by
the
power
take­
off
from
a
John
Deere
2750
diesel
tractor.
The
500­
gallon
tank
had
2
manifolds,
each
with
8
nozzles
operating
at
approximately
185­
200
pounds
per
square
inch
pressure.

Spray
Volume:
The
spray
volume
was
reported
to
be
approximately
77.5
or
74.2
gal
finished
spray
per
acre.
According
to
the
product
label,
the
test
substance
should
be
applied
using
an
adequate
spray
volume
to
cover
the
foliage.

Equipment
Calibration:
According
to
the
Study
Report,
the
sprayer
was
calibrated
before
each
application
by
the
time/
distance/
volume
output
method
with
a
verified
flowmeter
to
achieve
a
nominal
rate
of
3
lb
ai/
A..
Based
on
recorded
pass
times
versus
pass
times
calculated
for
the
row
lengths,
96%
and
100%
of
the
nominal
application
rate
were
achieved
in
the
first
and
second
applications,
respectively.

7.
Exposure
monitoring
methodology:

Urine:
Each
subject
was
issues
an
insulated
cooler
containing
two
labelled
1­
L
high
density
polyethylene
screw­
cap
wide­
mouth
bottles
for
urine
collection
and
two
frozen
gel
packs.
The
coolers
were
issued
at
the
beginning
of
the
monitoring
day
and
collected
at
the
close
of
the
monitoring
day.
A
second
cooler
with
empty
bottles
was
issued
at
the
close
of
the
monitoring
day
for
the
collection
of
night
voids
and
the
first
morning
void.
The
two
samples
comprised
one
urine
monitoring
day.
Urine
samples
were
placed
into
a
freezer
at
Page
15
of
43
the
staging
area,
transferred
to
freezers
at
SEAdR,
and
stored
frozen
until
they
were
shipped
frozen
to
PTRL
West
via
a
FedEx
freezer
truck.

8.
Dislodgeable
Foliar
Residue
Sampling
Procedures
Method
and
Equipment:
Samples
were
collected
with
a
Birkestrand­
type
leaf
punch
sampler
with
a
disk
diameter
of
2.54
cm
(
1­
inch).

Sampling
Procedure:
The
leaf
samples
were
collected
directly
into
prelabelled
glass
jars
using
a
Birkestrand­
type
leaf
punch
sampler.
Each
sample
consisted
of
a
target
of
40
leaf
disks.
The
leaf
disk
sampler
was
cleaned
with
water
and
then
acetone
between
each
subsample.
Sample
jars
were
placed
into
coolers
containing
"
blue
ice"
in
the
field
and
were
dislodged
within
4
hours
of
collection.
Additional
nontreated
control
samples
were
collected
from
nontreated
orchards
(
location
not
specified).

Surface
area
sampled
(
two
sides):
The
double
sided
surface
area
per
leaf
punch
was
approximately
10
cm2.

Total
Surface
Area
per
Replicate:
The
total
surface
area
per
replicate
was
approximately
405
cm2.

Replicates
per
activity:
­
Replicates
per
sampling
time:
Each
sample
consisted
of
40
leaf
disks.

­
Number
of
sampling
times:
Five
replicate
samples
were
collected
one
day
before
the
second
application(
ED
­
3),
and
one
day
after
the
second
application
(
ED
­
1).
Ten
replicate
samples
were
collected
on
the
monitoring
day
(
ED
0;
2
days
postapplication).
The
Study
Author
also
collected
DFR
replicates
on
the
4
days
following
reentry,
resulting
in
a
total
of
7
sampling
days.

Times
of
sampling:
The
exact
time
of
day
used
for
DFR
sampling
was
not
reported.

Part(
s)
of
foliage
sampled:
The
samples
were
collected
from
the
leaves
of
the
trees.

C.
ANALYTICAL
METHODOLOGY:

1.
Sample
Extraction/
Detection:

Urine:

Extraction
method:
The
urine
samples
were
analyzed
for
sulfinyl
and
sulfonyl
phosmet
urinary
metabolites
using
a
KMnO4
oxidation
reaction
followed
by
C18
Solid
Phase
Extraction
cleanup
allowing
for
a
single
moiety
analysis
of
sulfonyl
by
LC/
MS/
MS.

Detection
methods:
Sample
analysis
was
performed
using
SCIEX
3000
Components
(
HPLC/
Turbo
Ion
Spray
Mode).
See
Table
4
for
specific
conditions.

Table
4.
Summary
of
LC/
MS/
MS
Conditions
for
Urine
Mode
HPLC/
Turbo
Ion
Spray
GC
Column
Supelco
Supelcosil
LC­
318
(
25
cm
x
4.6
mm,
5
µ
m
with
Supelcosil
LC
Page
16
of
43
Table
4.
Summary
of
LC/
MS/
MS
Conditions
for
Urine
318
pre­
column
Solvents
Solvent
A
=
Water
(
0.05%
formic
acid)
Solvent
B
=
Acetonitrile
(
0.05%
formic
acid)

Time
(
min.)
Flow
Rate
(
mL/
min.)
%
A
%
B
0
0.50
98
2
13.0
0.50
37
63
13.5
1.3
0
100
17.0
1.3
0
100
17.5
1.0
98
2
25.0
1.0
98
2
25.5
0.5
98
2
Solvent
Program
26.0
0.5
98
2
Injection
Volume
10
µ
L
Ionization
mode
Turbo
spray
Divert
valve
to
mass
spectrophotometer
On
at
10.8
minutes,
off
at
13.0
minutes
Retention
Time
Sulfinyl
=
11.6
minutes
Sulfonyl
=
12.3
minutes
Method
Validation:
The
analytical
facility
developed
methods
for
the
SI
and
SO
metabolites
of
phosmet
in
human
urine
using
an
oxidation
reaction
(
SI
to
SO)
with
KMnO4
followed
by
a
C18
Solid
Phase
Extraction
cleanup
allowing
for
single
moiety
analysis
of
sulfonyl
by
LC/
MS/
MS.
The
analytical
laboratory
confirmed
methods
of
analysis
for
the
matrices
and
fully
supported
the
analysis
of
samples
with
controls
and
procedural
recoveries.
The
full
method
validation
report
is
provided
at
the
end
of
the
study.

Instrument
performance
and
calibration:
To
determine
instrument
calibration,
each
injection
sequence
was
typically
set
up
as
follows:
test
standard
injection,
0.02
µ
g/
mL
sulfonyl
calibrant,
solvent
blank
(
1:
9
acetonitrile:
water),
and
a
control
urine
sample.
After
that
run,
the
sequence
alternated
a
calibrant
injection
and
three
or
four
extract
samples
(
including
fortified
control
extracts,
concurrent
fortification
extracts,
field
fortification
extracts
and
urine
donor
sample
extracts).
The
final
injection
for
each
sample
set
sequence
was
a
quality
control
calibrant
injection
used
to
assess
the
stability
of
the
calibrant
response.
Representative
sulfinyl
and
sulfonyl
calibration
curves
and
LC/
MS/
MS
calibrant
chromatograms
are
presented
in
the
study.

Quantification:
The
mass
spectra
data
was
collected
and
quantitation
was
based
on
the
peak
area
of
the
daughter
ion
with
m/
z
176
from
the
parent
ion
m/
z
256
(
sulfonyl).
The
transition
of
240/
176
amu
was
monitored
for
confirmation
of
complete
oxidation
during
the
sample
Page
17
of
43
workup.
The
limit
of
quantitation
for
urine
analysis
was
0.025
µ
g/
mL
for
each
analyte
or
0.516
µ
g/
mL
for
the
sulfonyl
equivalence.
Blood:

Sample
Preparation:
Blood
samples
were
analyzed
for
plasma
and
red
blood
cell
cholinesterase
activity.
A
qualified
local
laboratory
could
not
be
located
to
perform
the
cholinesterase
assays
and
due
to
concerns
about
the
custody
and
integrity
of
the
blood
samples,
the
Study
Director
and
Sponsor's
Representative
chose
to
fractionate
the
blood
samples
into
plasma
and
saline­
washed
packed
red
blood
cells;
freeze
the
samples;
and
ship
the
frozen
samples
to
a
qualified
facility
at
the
conclusion
of
the
field
phase
of
the
study.
The
time
from
last
venipuncture
to
placement
into
the
mobile
freezer
was
less
than
four
hours.

Analysis:
The
plasma
samples
were
assayed
on
20
April
using
the
Ellman
photometric
method.
The
red
blood
cell
(
RBC)
samples
were
analyzed
for
RChe
on
20
and
21
April
also
using
a
method
based
on
the
Ellman
method.

Dislodgeable
Foliar
Residues:

Dislodging
Procedure:
The
residues
from
the
leaf
disks
were
dislodged
within
4
hours
of
collection.
Residues
were
dislodged
twice,
each
time
with
100
mL
of
0.01%
Aerosol
OT
in
distilled
water.
Each
sample
was
placed
on
a
reciprocating
shaker
operated
at
approximately
200
cycles
per
minute
for
10
minutes.
The
leaf
disks
were
counted
and
discarded
after
the
final
dislodging
and
both
100
mL
solutions
were
combined
into
a
single
sample
for
analysis.
The
samples
were
placed
in
frozen
storage
until
shipment
to
the
analytical
laboratory.

Detection
methods:
The
DFR
samples
were
analyzed
by
GC­
FPD
using
a
Model
No.
6890
Hewlett
Packard
Gas
Chromatograph
equipped
with
a
Hewlett
Packard
Flame
Photometric
Detector
(
FPD)
See
Table
5
for
specific
conditions.

Table
5.
Summary
of
GC­
FPD
Operating
Conditions
Column
DB­
5MS
Capillary
Column
15m
x
0.53
mm
i.
d.
x
1.5
µ
m
film
thickness
Gas
Flow
Rates
Carrier:
72.0
mL/
min.
(
Helium)
Detector:
133
mL/
min.
(
Hydrogen)
Detector:
128
mL/
min.
(
Air)
Detector
Makeup:
74
mL/
min.
(
Nitrogen)

Injector
Temperature
220
°
C
Detector
Temperature
225
°
C
Injection
Volume
4
µ
L,
by
Hewlett
Packard
7683
Autosampler
Inlet
Conditions
Injection
port
liner:
single­
gooseneck
liner
with
Restek
carbofrit
insert.
Splitless,
purge
flow
2
mL/
min.
@
2
minutes.

Oven
Temperature
Program
Initial
Temperature:
160
°
C
for
1
minute
Ramp:
160
°
C
to
260
°
C
at
15
°
C/
minute
(
hold
2
minutes)
Retention
Time:
~
5.3
minutes
for
Phosmet;
~
4.7
minutes
for
Phosmet
oxon
Page
18
of
43
Method
validation:
PTRL
West
validated
an
existing
analytical
method
for
the
determination
of
phosmet
and
phosmet
oxon
in
foliar
dislodging
solution.
Method
validation
recoveries
ranged
from
84.5%
to
90.2%
for
phosmet
and
from
88.8%
to
93.2%
for
phosmet
oxon.

Instrument
performance
and
calibration:
A
linear
regression
of
the
calibration
solutions
peak
area
vs.
concentration
for
each
analyte
was
determined
and
used
to
calculate
the
concentration
of
phosmet
and
phosmet
oxon
in
the
DFR
samples.
Sample
injections
were
bracketed
by
calibration
solution
injections
or
a
quality
control
calibrant
solution
injection.
Quality
control
calibrant
injections
were
analyzed
last
and
compared
to
the
relevant
calibrant
injections
used
in
the
quantitation
to
assess
the
stability
of
the
responses.

Quantification:
The
analytes
were
identified
by
the
coincidence
of
their
retention
times
with
that
of
reference
standard
calibration
solutions.
Phosmet
and
phosmet
oxon
were
quantified
by
integration
of
the
GC/
FPD
peak
areas
for
each
analyte
in
the
samples.
The
limit
of
quantitation
for
DFR
samples
is
1.0
µ
g/
mL
for
phosmet
and
0.2
µ
g/
mL
for
phosmet
oxon.

2.
Quality
Control:

Lab
Recovery:

Urine:
Concurrent
laboratory
urine
fortification
sample
recoveries
are
summarized
in
Table
6
below.
Each
sample
set
included
two
concurrent
fortified
urine
samples
fortified
with
both
sulfinyl
and
sulfonyl.
The
fortification
levels
were
the
following:
0.025
µ
g/
mL,
0.05
µ
g/
mL,
0.10
µ
g/
mL,
and
0.25
µ
g/
mL.
In
addition,
each
sample
set
(
except
day
1
and
2)
included
two
fortified
control
urine
extract
samples
that
were
fortified
with
sulfonyl
only,
at
0.5
µ
g/
mL
and
0.2
µ
g/
mL.
The
control
urine
used
for
each
sample
set
was
an
unfortified
field
fortification
sample.
Concurrent
fortification
sample
recoveries
ranged
from
62%
to
119%
with
an
overall
recovery
of
90
±
14%
recovery.
Control
extract
fortification
sample
recoveries
ranged
from
76%
to
122%
with
an
overall
recovery
of
104
±
10%.

Table
6.
Concurrent
Laboratory
Urine
Fortification
Recoveries
Urine
Sample
Set
Sulfinyl
Fortification
(
ug/
mL)
Sulfonyl
Fortification
(
ug/
mL)
Total
Sulfonyl
Fortification
Equivalence
(
ug/
mL)
1
Sulfonyl
Detected
(
ug/
mL)
Sulfonyl
Recovery
(%)

0.025
0.025
0.052
0.046
90%
Days
1
and
2
0.05
0.05
0.103
0.083
80%
0.025
0.025
0.052
0.055
106%
Day
2A
0.25
0.25
0.517
0.389
75%
0.025
0.025
0.052
0.054
104%
Day
2B
0.25
0.25
0.517
0.433
84%
0.025
0.025
0.052
0.052
101%
Day
4A
0.25
0.25
0.517
0.429
83%
Day
4B
0.025
0.025
0.052
0.060
117%
Page
19
of
43
Table
6.
Concurrent
Laboratory
Urine
Fortification
Recoveries
Urine
Sample
Set
Sulfinyl
Fortification
(
ug/
mL)
Sulfonyl
Fortification
(
ug/
mL)
Total
Sulfonyl
Fortification
Equivalence
(
ug/
mL)
1
Sulfonyl
Detected
(
ug/
mL)
Sulfonyl
Recovery
(%)

0.25
0.25
0.517
0.469
91%
0.025
0.025
0.052
0.055
106%
Day
5A
0.25
0.25
0.517
0.395
77%
0.025
0.025
0.052
0.061
118%
Day
5B
0.25
0.25
0.517
0.459
89%
0.05
0.05
0.103
0.094
91%
Day
6A
0.25
0.25
0.517
0.427
83%
0.05
0.05
0.103
0.095
92%
Day
6B
0.25
0.25
0.517
0.403
78%
0.05
0.05
0.103
0.092
89%
Day
7A
0.25
0.25
0.517
0.410
79%
0.025
0.025
0.052
0.050
97%
Day
7B
0.1
0.1
0.207
0.179
86%
0.10
0.1
0.207
0.129
62%
Day
8A
0.025
0.025
0.052
0.036
69%
0.025
0.025
0.052
0.048
93%
Day
8B
0.10
0.1
0.207
0.148
72%
0.025
0.025
0.052
0.055
106%
Day
9A
0.10
0.1
0.207
0.182
88%
0.025
0.025
0.052
0.058
112%
Day
9B
0.10
0.1
0.207
0.165
80%
Average
90%
Std.
Dev.
14%
1
Total
sulfonyl
equivalence
=
sulfonyl
fortification
(
µ
g/
mL)
+
(
sulfinyl
fortification
(
µ
g/
mL)
x
(
257/
241)
where
257/
241
=
the
molecular
weight
ratio
of
sulfonyl
÷
sulfinyl.

DFR:
Concurrent
laboratory
DFR
fortification
sample
recoveries
are
summarized
in
Table
7.
Each
sample
set
included
two
concurrent
fortified
DFR
samples
and
a
control
sample.
Duplicate
concurrent
fortification
samples
were
analyzed
with
each
set;
each
sample
in
the
set
was
fortified
with
phosmet
and
phosmet
oxon.
For
set
1,
the
concurrent
fortification
samples
were
fortified
at
1.0
µ
g/
mL
phosmet
and
0.2
µ
g/
mL
phosmet
oxon.
For
sets
2
through
7,
the
concurrent
fortification
samples
were
fortified
at
10.0
µ
g/
mL
phosmet
and
2.0
µ
g/
mL
phosmet
oxon.
Overall
recovery
of
phosmet
and
phosmet
oxon
from
all
concurrent
fortification
samples
was
88.2
±
2.8%
and
98.4
±
4.2%,
respectively.
No
phosmet
or
phosmet
oxon
was
detected
in
the
control
sample
analyzed
with
each
set,
with
the
exception
of
set
4
and
set
5
where
0.13
µ
g
and
0.12
µ
g
phosmet
was
detected.
For
these
sets,
concurrent
fortification
recoveries
were
corrected
for
the
phosmet
detected
in
the
control
samples.
Page
20
of
43
Table
7.
Concurrent
Laboratory
DFR
Fortification
Recoveries
Fortification
Level
Percent
Recovered
Sample
Set
Phosmet
(
ug/
mL)
Phosmet
Oxon
(
ug/
mL)
Phosmet
Detected
(
ug/
mL)
Phosmet
Oxon
Detected
(
ug/
mL)
Phosmet
Detected
(
ug/
cm2)
Phosmet
Oxon
Detected
(
ug/
cm2)
Phosmet
Phosmet
Oxon
1.0
0.2
0.902
0.196
0.445
0.097
90.2%
98.0%
DFR
set
1
1.0
0.2
0.920
0.198
0.454
0.098
92.0%
99.0%
10.0
2.0
9.205
1.862
4.546
0.920
92.1%
93.1%
DFR
set
2
10.0
2.0
9.153
1.841
4.520
0.909
91.5%
92.1%
10.0
2.0
8.568
2.003
4.231
0.989
85.7%
100.2%
DFR
set
3
10.0
2.0
8.918
2.049
4.404
1.012
89.2%
102.5%
10.0
2.0
8.591
2.102
4.242
1.038
85.9%
105.1%
DFR
set
4
10.0
2.0
8.411
2.098
4.154
1.036
84.1%
104.9%
10.0
2.0
8.396
2.000
4.146
0.988
84.0%
100.0%
DFR
set
5
10.0
2.0
8.651
2.002
4.272
0.989
86.5%
100.1%
10.0
2.0
8.600
1.818
4.247
0.898
86.0%
90.9%
DFR
set
6
10.0
2.0
8.908
1.947
4.399
0.961
89.1%
97.4%
10.0
2.0
8.936
1.975
4.413
0.975
89.4%
98.8%
DFR
set
7
10.0
2.0
8.978
1.927
4.434
0.952
89.8%
96.4%
Average
88.2%
98.4%
Std.
Dev.
2.7%
4.2%

Field
recovery:

Urine:
Urine
field
fortification
samples
were
analyzed
on
ED­
6,
ED­
5,
ED­
2,
ED+
0,
ED+
1,
ED+
2,
ED+
3,
and
ED+
4.
For
ED­
6
field
fortification
samples,
a
control
and
two
samples
fortified
in
the
field
with
sulfinyl
only
and
two
samples
fortified
in
the
field
with
sulfonyl
only
were
analyzed.
For
ED­
5
samples,
a
control
and
one
sample
fortified
with
both
analytes
and
two
samples
fortified
with
either
sulfinyl
or
sulfonyl
only
were
analyzed.
For
days
ED+
0
through
ED+
4
samples,
a
control
sample
was
analyzed
as
well
as
duplicate
field
fortification
samples
fortified
with
sulfinyl
and
sulfonyl
at
two
levels.
No
detectable
residues
were
found
in
the
control
field
fortification
samples
analyzed.

The
Study
Author
excluded
seven
samples
with
recovery
values
<
50%
from
their
overall
field
fortification
recovery.
Excluding
these
apparently
misfortified
samples,
the
Study
Author
reported
an
overall
field
fortification
recovery
of
103
±
15%.
Versar
included
all
reported
recovery
values,
which
resulted
in
an
overall
field
fortification
recovery
of
84
±
38%
recovery.
A
summary
of
the
field
fortification
recoveries
are
reported
in
Table
8.
Page
21
of
43
Table
8.
Urine
Field
Fortification
Samples
Collection
Day
(
postapp.)
Urine
Volume
(
mL)
Sulfinyl
Fortification
(
ug)
Sulfonyl
Fortification
(
ug)
Total
Sulfonyl
Fortification
Equivalence
(
ug)
1
Sulfonyl
Detected
(
ug)
2
Percent
Recovered
520
25
0
26.7
32.6
122%
465
50
0
53.3
52.8
99%
420
0
15
15.0
17.2
115%
ED­
6
507
0
25
25.0
26.7
107%
505
25
15
41.7
43.6
105%
526
0
50
53.3
54.7
103%
ED­
5
470
25
0
25.0
25.1
100%
536
25
15
41.7
54.7
131%
492
50
25
78.3
7.0
9%
568
25
15
41.7
45.7
110%
ED­
2
440
50
25
78.3
89.0
114%
538
125
60
193.3
206.7
107%
515
125
60
193.3
192.0
99%
440
250
100
366.6
396.5
108%
ED+
0
457
250
100
366.6
347.5
95%
435
250
100
366.6
318.5
87%
440
125
60
193.3
197.0
102%
325
125
60
193.3
27.6
14%
ED+
1
508
250
100
366.6
350.0
95%
407
125
60
193.3
213.8
111%
487
250
100
366.6
428.8
117%
440
250
100
366.6
179.3
49%
ED+
2
508
125
60
193.3
59.0
31%
352
50
25
78.3
70.2
90%
502
25
15
41.7
32.3
78%
315
25
15
41.7
5.3
13%
ED+
3
350
50
25
78.3
5.2
7%
521
25
15
41.7
44.9
108%
440
50
25
78.3
8.1
10%
480
50
25
78.3
47.8
61%
ED+
4
507
25
15
41.7
46.6
112%
Average
(
excluding
the
fortification
with
values
<
50%)
103%
Std.
Dev
15%
Average
(
including
all
samples)
84%
Std.
Dev.
38%
1
Total
sulfonyl
equivalence
=
sulfonyl
fort.
(
ug/
mL)
+
sulfinyl
fort.
(
ug/
mL)
x
(
257/
241)
where
257/
241
=
the
molecular
weight
ratio
of
sulfonyl/
sulfinyl
2
The
sulfonyl
values
reported
for
the
first
two
days
postapplication
in
Table
VII
(
page
181)
of
the
study
report
differ
from
the
values
presented
in
Table
7
(
page
32)
of
the
redacted
report.
Versar
was
informed
by
the
study
author
that
the
values
reported
in
the
redacted
report
were
incorrect
due
to
data
entry
error;
therefore;
the
values
reported
in
this
table
are
from
Table
VII
(
page
181)
of
the
study
report.
Page
22
of
43
DFR
DFR
field
fortification
samples
were
collected
from
monitoring
days
ED­
6,
ED­
5,
ED+
2,
ED+
3,
and
ED+
4.
For
each
of
these
days,
a
control
field
fortification
sample
was
analyzed
as
well
as
two
field
fortification
samples
fortified
with
phosmet
only
(
at
two
different
levels)
and
two
samples
fortified
with
phosmet
oxon
only
(
at
two
different
levels).
No
detectable
residues
were
found
in
the
day
ED­
6
and
ED­
5
control
field
fortification
samples
analyzed.
Low
levels
of
phosmet
were
detected
in
day
ED+
2,
ED+
3,
and
ED+
4
control
field
fortification
samples
(<
0.01
µ
g/
mL).

The
study
author
excluded
one
sample
with
a
recovery
values
of
25.1%
from
their
overall
field
fortification
recovery.
Excluding
this
outlier,
the
study
author
reported
an
overall
field
fortification
recovery
of
83.0%
for
phosmet
and
91.7%
for
phosmet
oxon.
A
summary
of
the
field
fortification
recoveries
are
reported
in
Table
9.

Table
9.
DFR
Field
Fortification
Recoveries
Fortification
(
ug/
mL)
Residues
Detected
(
ug/
mL)
Fortification
(
ug/
cm2)
Residues
Detected
(
ug/
cm2)
Percent
Recovery
Collection
Day
DFR
Volume
(
mL)
Phosmet
Phosmet
Oxon
Phosmet
Phosmet
Oxon
Phosmet
Phosmet
Oxon
Phosmet
Phosmet
Oxon
Phosmet
Phosmet
Oxon
198
8.84
6.828
4.365
3.372
77.3%

200
10.00
9.085
4.938
4.486
90.9%

196
0.026
0.024
0.013
0.012
94.1%
ED­
6
198
0.025
0.025
0.012
0.012
99.0%

196
7.65
6.515
3.779
3.217
85.1%

193
9.07
7.130
4.478
3.521
78.6%

196
0.026
0.025
0.013
0.012
98.0%
ED­
5
193
0.052
0.039
0.026
0.019
75.3%

192
5.21
3.002
2.572
1.482
57.6%

195
6.41
4.766
3.166
2.354
74.3%

192
0.052
0.043
0.026
0.021
82.6%
ED+
2
192
0.078
0.063
0.039
0.031
80.6%

195
3.85
0.964
1.899
0.476
25.1%

200
5.00
4.262
2.469
2.105
85.2%

190
0.079
0.050
0.039
0.025
63.3%
ED+
3
194
0.103
0.093
0.051
0.046
90.2%

197
3.81
2.906
1.880
1.435
76.3%

196
5.10
3.879
2.520
1.916
76.0%

197
0.076
0.056
0.038
0.028
73.5%
ED+
4
196
0.102
0.082
0.050
0.040
80.4%

Average
Recovery
(
excluding
sample
<
50%)
83.0%
91.7%

Tank
mix:
Tank­
mix
samples
were
not
collected
during
the
application
of
the
test
product.

Travel
Recovery:
Information
on
travel
recovery
was
not
reported.
Page
23
of
43
Storage
Stability:
The
study
author
reported
that
the
sulfonyl
analyte
was
found
to
be
stable
in
the
final
extracts
when
stored
for
18
days
in
a
freezer.
Field
fortification
sample
extracts
from
day
4
were
re­
analyzed
with
the
day
8B
sample
set.
Re­
analysis
of
the
extracts
for
concurrent
fortified
samples
1
and
2
and
day
4
field
fortification
gave
recoveries
of
99%,
80%
and
114%,
respectively
where
initial
analysis
gave
recoveries
of
102%,
83%
and
110%,
respectively.
All
final
extract
samples
were
analyzed
within
18
days
of
extraction
and
were
stored
in
a
freezer
when
not
analyzed
directly.

II.
RESULTS
AND
CALCULATIONS:

A.
EXPOSURE
CALCULATIONS:

Urinary
Metabolites
Phosmet­
equivalent
residue
was
estimated
by
the
Study
Authors
by
measurement
of
the
sulfonyl
and
sulfinyl
metabolites
of
phosmet
in
24
hour
urine
samples
collected
for
five
consecutive
days
beginning
on
the
morning
of
postapplication
reentry.
The
Study
Authors
report
that
worker
compliance
with
collection
of
24
hour
urine
samples
was
"
excellent
to
poor".
They
discuss
the
difficulties
encountered
in
getting
some
of
the
workers
to
comply
with
proper
collection
procedures.
This
difficulty
led
to
the
use
of
multipliers
to
adjust
metabolite
concentrations
for
incomplete
sample
collection.
The
Study
used
a
creatinine
correction
strategy
outlined
in
Mage
et.
al.
(
2004).
Expected
creatinine
concentration
was
modelled
as
a
function
of
a
person's
age,
gender,
and
body
surface
area
according
to
the
following
formulas:

Male
µ
g
Cn/
day
=
1.93(
140­
age[
year])
*
wt[
kg]
1.5*
ht[
cm]
0.5
Female
µ
g
Cn/
day
=
1.64(
140­
age[
year])
*
wt[
kg]
1.5*
ht[
cm]
0.5
Urinary
creatinine
levels
determined
in
the
samples
was
compared
to
the
expected
urinary
creatinine
for
each
individual
at
each
sampling
event.
Based
on
this
estimate
of
expected
creatinine,
an
adjustment
factor
(
ranging
from
0.64
to
4.38)
was
applied
to
the
sulfonyl
concentration
in
each
urine
collection
and
residues
were
estimated
by:

Creatinine
adjusted
sulfonyl
=
measured
sulfonyl
*
adjustment
factor
Reported
phosmet
equivalents
(
ug/
day)
=
corrected
SO
(
ug/
day)
*
adjustment
factor
*
1.235
molecular
weight
conversion
to
phosmet
equivalents.
Molecular
weight
of
phosmet
(
317.33)
and
molecular
weight
of
sulfonyl
(
257).
No
pharmacokinetic
factors
were
utilized
in
this
calculation.

Table
10
provides
a
summary
of
SO
residues
assayed
in
the
urine
samples
and
the
corresponding
creatinine­
adjusted
potential
phosmet­
equivalents
excreted
per
day
as
calculated
by
the
Study
Author.
The
reported
phosmet­
equivalents
do
not
take
into
consideration
the
pharmacokinetics
of
phosmet
metabolism.
Over
half
of
the
pre­
exposure
samples
showed
no
detectable
level
of
SO
residue
in
the
urine.
The
total
post­
exposure
phosmet
equivalents
ranged
from
1031
µ
g/
day
(
worker
G)
to
9488
µ
g/
day
(
worker
J).
The
highest
daily
concentrations
was
generally
found
on
the
first
exposure
day
(
ED
0),
although
four
of
the
sixteen
workers
demonstrated
the
highest
urine
levels
on
the
second
exposure
day
(
ED
+
1).
Levels
steadily
decreased
during
the
monitoring
period;
however,
the
levels
did
not
reach
preexposure
levels
by
the
end
of
the
sample
collection
period.

Cholinesterase
Activity
A
laboratory
qualified
to
perform
immediate
cholinesterase
assays
was
not
available
near
the
test
site.
Therefore
the
Study
Director
chose
to
separate
the
blood
samples
into
plasma
and
red
blood
cells.
The
red
blood
cells
were
washed
with
saline
and
both
fractions
were
stored
and
shipped
frozen
to
LabCorp
in
North
Carolina.
The
samples
were
assayed
on
20
and
21
April
using
assays
based
on
the
Ellman
photometric
method.
Page
24
of
43
Plasma
Cholinesterase
Activity:

Plasma
samples
were
divided
into
two
sets
(
subsample
set
"
a"
and
subsample
set
"
b").
All
subsample
"
a"
tubes
were
assayed
along
with
randomly
selected
subsample
"
b"
tubes
(~
19%).
The
27
duplicate
samples
(
subsample
"
b")
averaged
0.4%
greater
than
the
corresponding
"
a"
subsamples,
with
a
standard
deviation
of
±
2.4%.
Mean
values
ranged
from
2,699
U/
L
(
ED
­
2)
to
3,406
U/
L
(
ED
+
1).
An
analysis
of
variance
showed
no
significant
differences
between
days
for
the
subsample
"
a"
assays.
The
activity
of
the
positive
ChE
controls
at
the
beginning
and
end
of
the
run
(
2
each)
were
near
the
expected
mean
and
were
well
within
specifications.
The
Study
Author
reported
no
remarkable
findings
and
no
exposure­
related
depression
of
PChe.
A
summary
of
the
results
is
presented
in
Table
10.

Red
Blood
Cell
Cholinesterase
Assays:

Mean
values
of
the
RChe
samples
ranged
from
2,849
U/
L
(
ED
­
6)
to
5,229
U/
L
(
ED
+
4).
The
study
director
noticed
that
the
SOP
was
not
being
followed
after
the
first
set
of
28
had
been
prepared.
The
technician
attempted
to
recover
the
samples
and
hemolyze
the
samples,
but
forgot
the
vortexing
steps.
There
was
also
a
concern
that
a
vortexing
step
might
have
been
left
out
of
the
remaining
samples.
Therefore,
the
results
of
the
first
28
samples
were
compromised
and
there
was
uncertainty
about
the
remaining
samples.
The
study
author
decided
to
complete
a
subsample
"
b"
set
the
following
day.
A
summary
of
the
results
is
presented
in
Table
10.
The
RChe
results
were
more
variable
than
the
PChe
results.
The
RChe
activity
on
ED­
6
was
markedly
lower
than
on
other
days.
This
was
explained
as
normal
population
variance
as
the
handling
of
samples
was
similar.
An
analysis
of
variance
with
and
without
the
Bonferroni
correction
at
the
p=<
0.05
level
showed
some
significant
differences
among
some
day­
wise
comparisons.
Most
were
associated
with
the
lower
values
on
ED
­
6.
The
Study
Author
reports
no
remarkable
findings
and
no
exposure­
related
depression
of
RChe.

DFR:

Dislodgeable
foliar
residue
(
DFR)
was
examined
on
the
day
before
the
second
application,
the
day
of
the
second
application
(
2
days
prior
to
reentry
activity)
and
for
the
following
five
days
(
i.
e.,
7
monitored
days).
The
Study
Author
concluded
that
the
continuing
hard
rain
at
the
end
of
the
exposure
day
had
affected
the
dissipation
kinetics
and
reported
that
a
meaningful
dissipation
curve
could
not
be
developed.
The
residues
on
the
day
of
second
application
and
the
following
day
demonstrated
residues
comparable
to
previous
phosmet
DFR
studies.
The
phosmet
DFR
on
days
1
and
2
postapplication
averaged
5.9
ug/
cm2
and
5.0
ug/
cm2
,
respectively.
Phosmet
oxon
DFR
on
days
1
and
2
postapplication
averaged
0.012
ug/
cm2
and
0.010
ug/
cm2
,
respectively.
DFR
sampling
also
occurred
on
the
subsequent
4
days.
By
the
6th
day
after
application
DFR
levels
declined
to
0.7
ug/
cm2
and
0.004
ug/
cm2
for
phosmet
and
phosmet
oxon,
respectively.
A
summary
of
the
DFR
results
is
presented
in
Table
11.
The
residue
levels
were
corrected
for
field
fortification
recovery
values.
25
TABLE
10.
Summary
of
Postapplication
Biomonitoring
Data
 
Phosmet
Treated
Peach
Trees
Worker
ID
Clothing
Body
Weight
kg
Day
of
Collectiona
24
hour
Urine
Volumeb
mL/
day
Cnc
mg/
mL
Cn
mg/
day
Adjustment
Factord
SO
residuee
ug/
mL
SO
residuef
ug/
day
Reported
Phosmet
equivalentg
(
ug/
day)
Plasma
ChE
Activity
(
U/
L)
RBC
ChE
Activity
(
U/
L)

ED­
6
3,323
3,712
ED­
5
295
1.12
330
4.38
0.045
13
72
3,425
5,384
ED­
3
3,468
4,608
ED­
2
920
1.27
1,168
1.24
0.016
15
23
3,289
5,151
ED
0
930
1.23
1,143
1.27
0.427
397
621
3,055
5,518
ED+
1
1,140
0.97
1,102
1.31
0.181
206
335
3,354
4,369
ED+
2
1,240
0.87
1,078
1.34
0.097
120
199
3,277
4,343
ED+
3
1,070
1.00
1,075
1.35
0.042
45
75
3,408
5,022
A
(
male)

Ht
168
cm
Age
34
Denim
jacket,

Long
sleeves,
hat,

denim
pants,
leather
shoes
(
Jacket
removed
after
lunch)
66.8
ED+
4
1,350
0.83
1,126
1.28
0.051
69
109
3,212
4,849
TOTAL
POST
EXPOSURE
PHOSMET
FOR
WORKER
A
1,339
ED­
6
3,352
706
ED­
5
1,430
1.24
1,773
1.36
0.047
67
113
3,499
4,120
ED­
3
3,522
4,470
ED­
2
1,450
1.22
1,769
1.36
0.024
35
58
3,354
4,683
ED
0
1,780
0.79
1,410
1.71
0.727
1294
2,728
3,432
4,987
ED+
1
1,940
0.65
1,267
1.90
0.219
425
997
3,441
4,510
ED+
2
1,710
1.00
1,705
1.41
0.17
291
507
3,553
4,857
ED+
3
780
1.69
1,321
1.82
0.088
69
154
3,476
4,430
B
(
male)

Ht
163
cm
Age
28
Long
sleeves,

cap,
twill
pants,
leather
shoes
91.4
ED+
4
1,570
1.26
1,975
1.22
0.111
174
262
3,545
6,871
TOTAL
POST
EXPOSURE
PHOSMET
FOR
WORKER
B
4,648
26
TABLE
10.
Summary
of
Postapplication
Biomonitoring
Data
 
Phosmet
Treated
Peach
Trees
Worker
ID
Clothing
Body
Weight
kg
Day
of
Collectiona
24
hour
Urine
Volumeb
mL/
day
Cnc
mg/
mL
Cn
mg/
day
Adjustment
Factord
SO
residuee
ug/
mL
SO
residuef
ug/
day
Reported
Phosmet
equivalentg
(
ug/
day)
Plasma
ChE
Activity
(
U/
L)
RBC
ChE
Activity
(
U/
L)

ED­
6
3,276
4,115
ED­
5
215
1.47
316
4.29
0.043
9
49
3,343
5,233
ED­
3
3,514
5,022
ED­
2
550
1.85
1,018
1.33
0.009
5
8
3,471
5,577
ED
0
990
1.34
1,322
1.03
1.258
1245
1,579
3,168
5,884
ED+
1
540
1.43
770
1.76
1.442
779
1,695
3,419
5,023
ED+
2
670
1.22
819
1.66
0.701
470
961
NS
NS
ED+
3
520
1.72
895
1.52
0.208
108
203
3,447
5,108
C
(
male)

Ht
160
cm
Age
19
Long
sleeve
over
short
sleeve
shirt,

cap,
cords,

soft
shoes.

(
Long
sleeve
shirt
59.5
ED+
4
780
1.93
1,509
0.90
0.116
90
101
3,290
5,810
TOTAL
POST
EXPOSURE
PHOSMET
FOR
WORKER
C
4,539
ED­
6
2,665
3,317
ED­
5
650
0.83
540
2.87
0.032
21
74
2,780
4,834
ED­
3
2,865
4,996
ED­
2
950
1.53
1,454
1.07
0.018
17
22
2,679
5,259
ED
0
600
1.77
1,061
1.46
0.164
98
177
2,569
3,922
ED+
1
1,295
1.37
1,775
0.87
0.599
776
836
2,658
4,853
ED+
2
1,740
0.99
1,717
0.90
0.228
397
442
2,757
5,195
ED+
3
1,540
1.02
1,572
0.98
0.105
162
197
2,720
5,252
D
(
male)

Ht
160
cm
Age
19
Coat,
long
sleeves,

khaki
pants,

soft
shoes.

(
Jacket
worn
round
waist
 
removed
after
2
hrs
work)
65
ED+
4
1,630
1.13
1,848
0.84
0.095
155
160
2,590
5,624
TOTAL
POST
EXPOSURE
PHOSMET
FOR
WORKER
D
1,812
ED­
6
3,258
3,158
ED­
5
710
0.89
632
2.23
0.033
23
65
3,094
5,884
ED­
3
3,381
4,548
ED­
2
850
1.35
1,148
1.23
0.023
20
30
3,373
5,638
ED
0
690
2.40
1,653
0.85
0.582
402
424
3,258
5,200
ED+
1
840
1.42
1,194
1.18
1.456
1223
1,786
3,218
5,305
ED+
2
1,165
1.38
1,608
0.88
0.556
648
702
3,125
5,864
ED+
3
510
1.17
598
2.36
0.374
191
556
3,287
4,712
E
(
male)

Ht
160
cm
Age
17
Long
sleeves,

jeans,
soft
shoes
60.5
ED+
4
1,050
2.10
2,210
0.64
0.066
69
55
3,102
4,702
TOTAL
POST
EXPOSURE
PHOSMET
FOR
WORKER
E
3,523
27
TABLE
10.
Summary
of
Postapplication
Biomonitoring
Data
 
Phosmet
Treated
Peach
Trees
Worker
ID
Clothing
Body
Weight
kg
Day
of
Collectiona
24
hour
Urine
Volumeb
mL/
day
Cnc
mg/
mL
Cn
mg/
day
Adjustment
Factord
SO
residuee
ug/
mL
SO
residuef
ug/
day
Reported
Phosmet
equivalentg
(
ug/
day)
Plasma
ChE
Activity
(
U/
L)
RBC
ChE
Activity
(
U/
L)

ED­
6
3,121
3,303
ED­
5
NS
NS
NS
NS
NS
NS
NS
2,985
5,327
ED­
3
3,027
4,871
ED­
2
1,400
1.01
1,414
1.23
0.019
27
40
3,065
4,539
ED
0
2,700
0.73
1,958
0.89
1.626
4390
4,811
3,009
2,585
ED+
1
1,355
1.14
1,539
1.13
0.965
1308
1,823
2,862
5,111
ED+
2
1,250
0.92
1,146
1.52
0.467
584
1,093
NS
NS
ED+
3
1,150
1.18
1,354
1.28
0.284
327
518
3,170
4,715
F
(
male)

Ht
165
cm
Age
18
2
short
sleeve
shirts,
cap,

jeans,
soft
shoes
69.1
ED+
4
1,940
0.71
1,368
1.27
0.123
239
374
2,958
5,657
TOTAL
POST
EXPOSURE
PHOSMET
FOR
WORKER
F
8,619
ED­
6
2,152
3,023
ED­
5
720
1.47
1,058
1.63
ND
ND
ND
2,227
5,459
ED­
3
2,558
5,853
ED­
2
1,110
1.16
1,288
1.34
ND
ND
ND
2,347
5,337
ED
0
1,000
1.39
1,393
1.24
0.235
235
361
2,391
2,437
ED+
1
1,410
1.18
1,658
1.04
0.234
330
425
2,323
5,702
ED+
2
800
1.40
1,120
1.54
0.061
49
93
2,468
5,151
ED+
3
710
1.66
1,182
1.46
0.041
29
53
2,532
6,135
G
(
female)

Ht
145
cm
Age
29
Long
sleeve
shirt,
short
sleeve
shirt,

linen
pants,

leather
shoes
(
long
sleeve
shirt
put
on
after
rains
started)
85.5
ED+
4
730
1.41
1,026
1.69
0.065
47
99
2,621
5,767
TOTAL
POST
EXPOSURE
PHOSMET
FOR
WORKER
G
1,031
28
TABLE
10.
Summary
of
Postapplication
Biomonitoring
Data
 
Phosmet
Treated
Peach
Trees
Worker
ID
Clothing
Body
Weight
kg
Day
of
Collectiona
24
hour
Urine
Volumeb
mL/
day
Cnc
mg/
mL
Cn
mg/
day
Adjustment
Factord
SO
residuee
ug/
mL
SO
residuef
ug/
day
Reported
Phosmet
equivalentg
(
ug/
day)
Plasma
ChE
Activity
(
U/
L)
RBC
ChE
Activity
(
U/
L)

ED­
6
3,419
3,507
ED­
5
1,350
1.25
1,688
0.86
0.038
51
54
3,315
5,813
ED­
3
3,333
4,716
ED­
2
1,055
1.32
1,393
1.04
0.013
14
18
3,538
5,023
ED
0
800
1.91
1,527
0.95
0.464
371
433
3,438
4,994
ED+
1
1,023
1.51
1,542
0.94
0.658
673
778
3,384
5,255
ED+
2
900
1.31
1,183
1.22
0.366
329
496
3,311
5,420
ED+
3
550
2.62
1,439
1.00
0.05
28
34
3,201
4,622
I
(
male)

Ht
160
cm
Age
40
Short
sleeves
over
knit
shirt,
cap,

jeans
70.5
ED+
4
500
2.56
1,281
1.13
0.017
9
12
3,069
4,244
TOTAL
POST
EXPOSURE
PHOSMET
FOR
WORKER
I
1,753
ED­
6
3,116
1,127
ED­
5
1,435
1.13
1,622
1.01
ND
ND
ND
3,074
4,224
ED­
3
3,236
5,123
ED­
2
950
1.54
1,463
1.12
0.025
24
33
3,245
4,431
ED
0
1,555
0.95
1,476
1.11
2.625
4082
5,611
3,184
3,155
ED+
1
1,925
0.86
1,650
1.00
0.768
1478
1,818
3,258
5,136
ED+
2
2,050
0.81
1,658
0.99
0.385
789
966
3,300
4,716
ED+
3
2,080
0.86
1,793
0.92
0.25
520
588
NS
NS
J
(
male)

Ht
168
cm
Age
34
Jacket
Long
sleeves,

cap,
jeans,

tennis
shoes
(
Jacket
removed
after
2
hrs
work)
72.7
ED+
4
2,400
0.76
1,822
0.90
0.189
454
505
3,132
4,229
TOTAL
POST
EXPOSURE
PHOSMET
FOR
WORKER
J
9,488
29
TABLE
10.
Summary
of
Postapplication
Biomonitoring
Data
 
Phosmet
Treated
Peach
Trees
Worker
ID
Clothing
Body
Weight
kg
Day
of
Collectiona
24
hour
Urine
Volumeb
mL/
day
Cnc
mg/
mL
Cn
mg/
day
Adjustment
Factord
SO
residuee
ug/
mL
SO
residuef
ug/
day
Reported
Phosmet
equivalentg
(
ug/
day)
Plasma
ChE
Activity
(
U/
L)
RBC
ChE
Activity
(
U/
L)

ED­
6
3,378
2,900
ED­
5
1,650
0.66
1,089
1.44
0.035
58
102
3,317
4,725
ED­
3
3,532
4,320
ED­
2
930
1.08
1,004
1.56
0.034
32
61
3,424
4,658
ED
0
1,660
0.51
852
1.83
0.911
1512
3,426
3,541
4,493
ED+
1
1,520
0.71
1,076
1.45
0.575
874
1,568
3,453
5,041
ED+
2
635
0.91
579
2.70
0.333
211
705
3,298
4,707
ED+
3
2,080
0.83
1,731
0.90
0.187
389
434
3,469
4,422
L
(
male)

Ht
170
cm
Age
19
Long
sleeve
shirt,
cap,

jeans,
bandana,

tennis
shoes
one
glove
(
glove
removed
in
late
afternoon)
64.1
ED+
4
480
1.88
904
1.73
0.12
58
123
3,402
4,425
TOTAL
POST
EXPOSURE
PHOSMET
FOR
WORKER
L
6,256
ED­
6
2,408
1,715
ED­
5
1,325
0.67
888
0.80
ND
ND
ND
2,380
5,760
ED­
3
670
1.40
938
0.76
ND
ND
ND
2,227
4,796
ED­
2
2,321
5,045
ED
0
1,350
0.62
842
0.84
0.462
624
648
2,161
4,511
ED+
1
600
0.34
205
3.46
0.118
71
302
2,555
5,500
ED+
2
760
1.14
867
0.82
0.236
179
181
2,421
5,187
ED+
3
1,020
1.08
1,105
0.64
0.1
102
81
2,281
4,410
M
(
male)

Ht
160
cm
Age
52
Long
sleeves,

tshirt
cap,

jeans,

tennis
shoes
47.7
ED+
4
1,130
0.79
898
0.79
0.069
78
76
2,402
5,711
TOTAL
POST
EXPOSURE
PHOSMET
FOR
WORKER
M
1,288
30
TABLE
10.
Summary
of
Postapplication
Biomonitoring
Data
 
Phosmet
Treated
Peach
Trees
Worker
ID
Clothing
Body
Weight
kg
Day
of
Collectiona
24
hour
Urine
Volumeb
mL/
day
Cnc
mg/
mL
Cn
mg/
day
Adjustment
Factord
SO
residuee
ug/
mL
SO
residuef
ug/
day
Reported
Phosmet
equivalentg
(
ug/
day)
Plasma
ChE
Activity
(
U/
L)
RBC
ChE
Activity
(
U/
L)

ED­
6
2,411
3,949
ED­
5
1,475
0.55
811
2.38
ND
ND
ND
2,325
5,167
ED­
3
2,437
4,745
ED­
2
340
1.71
581
3.32
ND
ND
ND
2,335
5,163
ED
0
950
1.31
1,246
1.55
1.392
1322
2,531
2,309
4,186
ED+
1
810
1.12
909
2.12
0.237
192
504
2,329
4,979
ED+
2
1,175
0.74
873
2.21
0.27
317
867
2,389
4,664
ED+
3
1,075
0.94
1,007
1.92
0.247
266
629
2,405
4,185
N
(
male)

Ht
168
cm
Age
32
Short
sleeves,

cap,
jeans,

hiking
boots
80
ED+
4
1,160
1.33
1,547
1.25
0.224
260
401
2,521
5,429
TOTAL
POST
EXPOSURE
PHOSMET
FOR
WORKER
N
4,932
ED­
6
2,528
1,686
ED­
5
750
0.85
638
1.60
ND
ND
ND
2,698
6,254
ED­
3
NS
NS
ED­
2
517
1.38
713
1.43
ND
ND
ND
2,715
5,508
ED
0
620
0.95
587
1.73
1.934
1199
2,568
2,744
2,968
ED+
1
660
0.69
458
2.22
0.767
506
1,389
2,788
4,532
ED+
2
870
1.00
873
1.17
0.253
220
317
2,608
4,503
ED+
3
740
0.83
616
1.65
0.131
97
198
2,564
5,607
O
(
male)

Ht
155
cm
Age
60
Short
sleeves,

cap,
pant,

tennis
shoes
65.5
ED+
4
760
0.63
478
2.13
0.169
128
338
NS
NS
TOTAL
POST
EXPOSURE
PHOSMET
FOR
WORKER
O
4,810
31
TABLE
10.
Summary
of
Postapplication
Biomonitoring
Data
 
Phosmet
Treated
Peach
Trees
Worker
ID
Clothing
Body
Weight
kg
Day
of
Collectiona
24
hour
Urine
Volumeb
mL/
day
Cnc
mg/
mL
Cn
mg/
day
Adjustment
Factord
SO
residuee
ug/
mL
SO
residuef
ug/
day
Reported
Phosmet
equivalentg
(
ug/
day)
Plasma
ChE
Activity
(
U/
L)
RBC
ChE
Activity
(
U/
L)

ED­
6
2,893
3,963
ED­
5
750
0.89
668
3.23
ND
ND
ND
2,958
4,950
ED­
3
NS
NS
ED­
2
517
1.38
713
3.03
0.021
11
41
2,766
4,361
ED
0
940
0.86
808
2.67
1.035
973
3,210
2,845
4,264
ED+
1
1,270
0.90
1,139
1.90
0.554
704
1,647
2,824
4,921
ED+
2
1,325
0.51
676
3.19
0.183
242
956
3,077
4,625
ED+
3
1,480
0.83
1,228
1.76
0.143
212
460
2,931
4,541
P
(
female)

Ht
155
cm
Age
45
Short
sleeves,
cropped
pants,
cloth
gloves
96.4
ED+
4
1,410
0.82
1,160
1.86
0.176
248
570
2,978
4,588
TOTAL
POST
EXPOSURE
PHOSMET
FOR
WORKER
P
6,843
ED­
6
3,296
783
ED­
5
1,225
1.00
1,225
1.22
ND
ND
ND
3,427
4,982
ED­
3
3,260
3,380
ED­
2
760
1.12
851
1.75
ND
ND
ND
3,218
3,276
ED
0
990
0.98
972
1.54
0.363
359
682
3,352
4,712
ED+
1
1,000
0.81
810
1.84
0.179
179
407
3,466
5,211
ED+
2
1,043
1.11
1,159
1.29
0.075
78
124
3,448
5,037
ED+
3
990
0.96
953
1.57
0.049
49
94
3,433
4,773
Q
(
male)

Ht
168
cm
Age
38
Long
sleeve
shirt,
cap,

jeans,
work
boots
70
ED+
4
1,070
0.98
1,052
1.42
0.12
128
225
3,277
5,051
TOTAL
POST
EXPOSURE
PHOSMET
FOR
WORKER
Q
1,532
32
TABLE
10.
Summary
of
Postapplication
Biomonitoring
Data
 
Phosmet
Treated
Peach
Trees
Worker
ID
Clothing
Body
Weight
kg
Day
of
Collectiona
24
hour
Urine
Volumeb
mL/
day
Cnc
mg/
mL
Cn
mg/
day
Adjustment
Factord
SO
residuee
ug/
mL
SO
residuef
ug/
day
Reported
Phosmet
equivalentg
(
ug/
day)
Plasma
ChE
Activity
(
U/
L)
RBC
ChE
Activity
(
U/
L)

ED­
6
3,368
4,610
ED­
5
1,150
1.70
1,955
1.65
ND
ND
ND
3,469
5,163
ED­
3
3,424
2,774
ED­
2
670
2.28
1,528
2.11
ND
ND
ND
3,520
4,839
ED
0
1,065
1.76
1,870
1.72
0.37
394
837
2,794
5,078
ED+
1
1,075
1.70
1,824
1.76
0.18
194
421
3,434
4,625
ED+
2
1,050
1.29
1,351
2.38
0.144
151
445
3,380
4,865
ED+
3
1,350
1.34
1,808
1.78
0.062
84
184
3,514
4,367
R
(
male)

Ht
170
cm
Age
40
Long
sleeves,

cap,
jeans,

boots
(
shirt
cuffed
up
after
20
min
work)
117.7
ED+
4
660
1.84
1,214
2.65
0.178
117
384
3,421
5,483
TOTAL
POST
EXPOSURE
PHOSMET
FOR
WORKER
R
2,271
Note:
The
results
for
samples
collected
following
re­
entry
exposure
are
shaded
in
the
table.

NS
=
no
sample
collected
ND
=
Non­
detected
a
Date
specimen
collected
in
relation
to
exposure
(
e.
g.,
ED­
6
represents
the
results
on
samples
collected
6
days
pre­
exposure,
ED
0
represents
the
day
of
reentry)

b
24
hour
urine
volumes
less
than
800
mL
are
highlighted
in
bold.

c
Cn
(
mg/
mL)
=
urinary
creatinine
level
d
Adjustment
Factor
=
Creatinine
concentration
was
modeled
as
a
function
of
a
person's
age,
gender,
and
body
surface
area
according
to
the
formulas
presented
in
Study
Report.

Male
µ
g
Cn/
day
=
1.93(
140­
age[
year])
*
wt[
kg]
1.5*
ht[
cm]
0.5
and
Female
µ
g
Cn/
day
=
1.64(
140­
age[
year])
*
wt[
kg]
1.5*
ht[
cm]
0.5
.

e
SO
(
ug/
mL)
=
daily
concentration
of
sulfonyl
metabolite
measured
in
urine.

f
SO
(
ug/
day)
=
SO
(
ug/
mL)
*
24
hour
urine
volume.

g
Reported
Phosmet
equivalents
(
ug/
day)
=
corrected
SO
(
ug/
day)
*
adjustment
factor
*
1.235
molecular
weight
conversion
to
Phosmet
equivalents.
Molecular
weight
of
phosmet
=
317.33
and
molecular
weight
of
sulfonyl
=
257.
This
value
has
been
adjusted
for
possible
incomplete
urine
collection
 
see
footnote
d.
No
pharmcokinetic
factors
have
been
utizilied
in
this
calculation.
33
Table
11.
Dislodgeable
Foliar
Residues
of
Phosmet
and
Phosmet
Oxon
Collection
Day
Phosmet
(
ug/
cm2)
Phosmet
Oxon
(
ug/
cm2)
Average
Phosmet
(
ug/
cm2)
Average
Phosmet
Oxon
(
ug/
cm2)

0.006
0.0016
0.016
0.0016
0.013
0.0016
0.010
0.0016
ED
­
3
Pre­
Application
0.002
0.0000
0.01
0.001
6.7
0.012
6.6
0.011
5.5
0.011
5.4
0.012
5.6
0.012
ED
­
2
Day
of
Second
Application
6.4
0.009
5.9
0.012
4.4
0.009
5.9
0.010
4.6
0.009
5.0
0.010
4.9
0.011
5.8
0.010
4.7
0.012
4.1
0.008
4.7
0.009
ED
0
Day
of
Exposure
(
2
days
after
second
application)

4.8
0.009
5.0
0.010
3.8
0.010
3.5
0.008
3.3
0.008
3.6
0.008
ED
+
1
(
3
days
after
second
application)

3.7
0.009
3.6
0.009
1.7
0.008
1.0
0.006
0.7
0.005
1.2
0.007
ED
+
2
(
4
days
after
second
application)

1.4
0.006
1.2
0.006
1.0
0.005
1.3
0.009
0.6
0.004
0.9
0.007
ED
+
3
(
5
days
after
second
application)

1.3
0.007
1.0
0.006
0.9
0.005
0.8
0.004
0.5
0.004
0.6
0.004
ED
+
4
(
6
days
after
second
application)

0.9
0.005
0.7
0.004
Phosmet
residues
were
corrected
for
an
average
field
fortification
of
83%
Phosmet
Oxon
residues
were
corrected
for
an
average
field
fortification
of
91.7%
34
III
DISCUSSION:

A.
LIMITATIONS
OF
THE
STUDY:

Major
issues
of
concern
in
evaluation
of
the
study
include:

 
Other
than
a
molecular
weight
factor
to
account
for
the
difference
in
molecular
weight
between
the
urinary
metabolite
sulfonyl,
and
the
active
ingredient
phosmet,
the
Study
Author
did
not
factor
any
pharmacokinetic
data
into
the
estimation
of
phosmet
equivalent
dose.
One
factor
typically
considered
in
the
estimate
of
dose
is
the
percentage
of
active
ingredient
converted
to
urinary
metabolite
and
subsequently
excreted
in
the
urine.
Another
factor
to
be
considered
is
the
percentage
of
metabolite
expected
to
be
excreted
during
the
sampling
time
period.
The
Study
Report
protocol
states
that
the
sulfinyl
and
sulfonyl
metabolites
of
phosmet
account
for
approximately
50­
60%
of
the
administered
radioactivity
in
urine
in
a
rat
oral
metabolism
study.
The
Authors
did
not
take
this
into
consideration
in
their
estimate
of
dose.

 
Many
of
the
24
hour
urine
collections
demonstrate
total
volumes
substantially
below
what
is
expected
for
normal,
healthy
adults.
The
volume
of
urine
produced
by
a
normal
adult
over
a
24
hour
period
typically
ranges
between
800
and
1800
mL
(
Tietz,
1970).
Sample
volumes
obtained
from
the
16
workers
against
this
standard
demonstrate
that
28
of
123
urine
collections
were
below
what
normally
would
be
expected.

 
The
Study
Authors
attempted
to
correct
for
incomplete
urine
collection.
They
adjusted
sulfonyl
concentration
in
the
urine
samples
using
a
technique
which
compared
measured
creatinine
to
expected
creatinine
for
each
individual
at
each
sampling
event
(
Mage
et
al.,
2004).
Based
on
this
estimate
of
expected
creatinine,
an
adjustment
factor
was
applied
to
the
sulfonyl
concentration
in
each
urine
collection.
Use
of
this
correction
strategy
resulted
in
adjustment
factors
ranging
from
0.64
to
4.38.
Use
of
factors
of
these
magnitudes
indicate
that
in
some
instances,
urine
volume
was
as
low
as
25%
of
the
expected
volume.

 
The
study
Authors
also
applied
the
adjustment
factor
to
those
samples
where
the
actual
creatinine
level
was
higher
than
the
expected
creatinine
level
(
e.
g.,
adjustment
factor
<
1.0).
This
had
the
effect
of
reducing
the
sulfonyl/
sulfinyl
that
was
actually
excreted
by
those
individuals.

 
The
DFR
analysis
was
most
likely
compromised
by
an
exposure
day
rainfall
event.
The
Study
Report
states
that
the
"
continued
hard
rain
at
the
end
of
the
exposure
day
had
affected
the
dissipation
kinetics
and
that
a
meaningful
dissipation
curve
could
not
be
developed."
The
study
authors
report
that
residue
levels
on
the
first
and
second
day
after
the
second
application
(
approximately
6
and
5
ug/
cm2,
respectively)
were
consistent
with
expected
DFR
values.
When
comparing
the
DFR
results
with
previously
conducted
phosmet
dissipation
regression
curves,
it
appears
that
residues
levels
determined
after
the
rain
event
demonstrate
significantly
lower
levels
than
those
expected.

 
In
the
afternoon
of
the
reentry
day,
postapplication
activities
were
cut
short
due
to
heavy
rain.
The
affect
of
this
event
on
the
phosmet
exposure
estimate
is
unknown.
It
is
possible,
however,
that
meaningful
exposure
was
affected.
The
rainfall
could
have
washed
the
transferable
residue
from
the
leaves,
and/
or
washed
residue
from
the
workers'
skin
and
clothing.
Or
it
is
possible
that
the
rain
would
solubilize
the
DFRs
making
them
more
readily
available
for
transfer,
or
the
water
mass
could
have
pushed
residues
through
the
clothing
to
skin
increasing
dermal
exposure,
or
the
damp
clothing
could
hydrate
the
skin,
possibly
enhancing
dermal
absorption.

 
Urinary
field
fortification
levels
were
inconsistent,
with
seven
samples,
or
25%,
demonstrating
recovery
values
less
than
50%.
The
Study
Author
deleted
these
values
from
the
calculation
of
average
recovery,
reporting
that
the
values
must
have
been
misfortified.
If
these
fortification
values
were
included
in
the
calculations,
overall
recovery
would
be
84%,
necessitating
the
use
of
a
correction
factor.

 
The
clothing
worn
by
the
workers
was
inconsistent.
It
is
difficult
to
accurately
characterize
exposure
in
these
circumstances.
Table
1
outlines
the
clothing
worn
by
the
individual
workers.
A
few
of
the
workers
wore
35
jackets
for
part
of
the
workday,
some
of
the
workers
wore
gloves,
some
wore
hats,
some
workers
wore
shortsleeved
shirts
and
others
wore
long­
sleeved
shirts.

 
Several
of
the
urine
samples
demonstrate
incomplete
oxidation
of
sulfinyl
metabolite
to
the
quantified
metabolite,
sulfonyl.
The
phosmet
equivalent
levels
are
based
on
measurement
of
sulfonyl
only.
The
Study
Authors
did
not
adjust
the
estimate
of
phosmet
concentration
to
account
for
this.

 
EPA
Reg
No.
10163­
169
specifies
a
maximum
use
rate
of
4.25
lbs.
ai/
A.
The
test
substance
was
applied
to
the
peach
trees
at
a
rate
of
3
lbs.
ai/
A.

 
Postapplication
activities
were
cut
short
(
i.
e.,
the
workers
worked
6.5
hours
on
the
day
of
exposure)
due
to
the
rainfall.

 
Creatinine
levels
were
determined;
however,
it
was
not
reported
if
the
specific
gravity
of
the
urine
was
analyzed.

 
It
is
not
well
established
that
washed
red
cells
can
be
frozen
for
a
period
of
approximately
one
month
and
then
assayed
for
RChe
activity,
as
was
the
case
in
this
Study.
The
laboratory
utilized
by
the
Study
Author
reports
that
their
RChe
method
was
validated
using
fresh
specimens
(
within
48
hours
of
collection)
for
estimation
of
RChe
activity.
The
analytical
lab
utilized
for
cholinesterase
testing
does
not
have
data
to
support
whether
or
not
frozen
storage
would
affect
stability.

 
This
study
was
conducted
at
only
one
test
site,
a
peach
orchard
in
Morven,
Georgia.
Therefore,
DFR
data
was
not
collected
from
at
least
three
geographically
distinct
locations
for
each
formulation
and
crop
type
as
specified
in
the
guidelines.
36
_________________________
____________________________
Name:
Name:
Evaluator
Peer
Reviewer
Occupational
Exposure
Assessment
Section
Occupational
Exposure
Assessment
Section
__________________
____________________
Date
Date
_________________________
Name:
Head,
Occupational
Exposure
Assessment
Section
_________________________
Date
37
APPENDIX
A
Compliance
Checklists
for
"
Biomonitoring
of
Workers
Hand­
thinning
Peaches
Treated
with
Phosmet
Insecticide"
38
COMPLIANCE
CHECKLIST
Compliance
with
OPPTS
Series
875,
Postapplication
Occupational
and
Residential
Exposure
Test
Guidelines,
Group
B:
Guidelines,
875.2600
(
Biological
monitoring)
is
critical.
The
itemized
checklist
below
describes
compliance
with
the
major
technical
aspects
of
OPPTS
875.2600.

875.2600:

 
The
Agency
requires
investigators
to
submit
protocols
for
review
purposes
prior
to
the
inception
of
the
study.
Adequate
pharmacokinetic
data
must
exist
to
effectively
interpret
the
data.
This
criterion
was
met.

 
Expected
deviations
from
GLPs
should
be
presented
concurrently
with
any
protocol
deviations
and
their
potential
study
impacts.
This
criterion
was
met.

 
The
test
substance
should
be
a
typical
end
use
product
of
the
active
ingredient.
This
criterion
was
met.

 
The
application
rate
used
in
the
study
should
be
provided
and
should
be
the
maximum
rate
specified
on
the
label.
However,
monitoring
following
application
at
a
typical
application
rate
may
be
more
appropriate
in
certain
cases.
This
criterion
was
not
met.
The
label
states
the
maximum
use
rate
is
4.25
lbs.
ai/
acre.
The
test
substance
was
applied
to
the
peach
trees
at
a
rate
of
3
lbs.
ai/
acre.

 
Selected
sites
and
seasonal
timing
of
monitoring
should
be
appropriate
to
the
activity.
This
criterion
was
met.

 
A
sufficient
number
of
replicates
should
be
generated
to
address
the
exposure
issues
associated
with
the
population
of
interest.
Specifically,
each
study
should
include
a
minimum
of
15
individuals
(
replicates)
per
activity.
This
criterion
was
met.

 
Test
subjects
should
be
regular
workers,
volunteers
trained
in
the
work
activities
required,
or
typical
homeowners.
This
criterion
was
met.

 
The
monitored
activity
should
be
representative
of
a
typical
working
day
for
the
specific
task
in
order
to
capture
all
related
exposure
activities.
This
criterion
may
not
have
been
met.
Meaningful
exposure
was
possibly
affected
by
rainfall
on
the
day
the
thinning
tasks
were
conducted.
In
the
afternoon
of
the
reentry
day,
postapplication
activities
were
cut
short
due
to
a
significant
rain
event.

 
The
exposure
monitoring
period
should
be
of
sufficient
length
to
ensure
reasonable
detectability
of
residues
in
biological
media
(
e.
g.,
blood
and
urine)
consistent
with
pharmacokinetic
data
such
as
excretion
profile,
duration
time,
etc.
This
criterion
was
met.

 
Biomonitoring
should
be
conducted
using
methodologies
based
on
the
pharmacokinetic
properties
of
the
pesticide
(
parent
compound
and
its
metabolites)
of
concern
(
e.
g.,
need
validated
pharmacokinetic
models
from
humans
or
appropriate
animal
surrogate
and
appropriate
route
of
exposure).
This
criterion
was
not
met.
The
study
author
did
not
account
for
the
pharmacokinetics
of
the
metabolite
when
estimating
phosmet
equivalents.

 
Any
protective
clothing
worn
by
study
participants
should
be
identified
and
should
be
consistent
with
the
product
label.
This
criterion
was
partially
met.
The
clothing
worn
by
the
participants
was
identified;
however,
the
test
subjects
wore
their
own
clothing
on
the
day
of
reentry,
resulting
in
inconsistent
work
apparel.
It
is
difficult
to
accurately
characterize
exposure
in
these
circumstances.
39
 
If
urine
monitoring
is
being
conducted,
urine
samples
should
be
collected
one
or
two
days
before
participating
in
the
applicator
exposure
monitoring
activities
and
should
continue
on
the
day
of
exposure
and
for
an
appropriate
time
period
after
these
activities
have
been
completed,
depending
on
the
excretion
kinetics
of
the
compound.
The
24­
hour
sample
collection
cycle
should
begin
with
the
first
void
after
beginning
work
activities
and
end
with
the
first
void
on
the
following
morning,
continuing
this
24­
hour
cycle
on
subsequent
days.
This
criterion
was
not
met.
It
appears
that
the
urine
sample
collections
were
incomplete.
28
of
123
urine
collections
were
below
what
normally
would
be
expected
in
a
normal
healthy
adult.

 
If
blood
monitoring
is
being
conducted,
baseline
blood
samples
should
be
collected
from
each
individual
prior
to
exposure.
Based
on
pharmacokinetics,
postapplication
exposure
samples
should
be
collected
at
the
appropriate
times
before,
during,
and
after
exposure.
This
criterion
was
met.

 
Materials
used
for
sample
collection
should
not
interfere
with
(
e.
g.,
absorb)
the
analytes
of
interest.
This
criterion
was
met.

 
Creatinine
levels
should
be
determined
as
a
way
of
qualitatively
monitoring
completeness
of
urine
collection
samples.
Specific
gravity,
as
another
measure
of
24­
hour
sample
completeness,
should
be
performed
as
soon
after
collection
as
possible
(
and
before
sample
storage).
These
criteria
were
partially
met.
Creatinine
levels
were
determined;
however,
it
was
not
reported
if
the
specific
gravity
of
the
urine
was
analyzed.

 
Prior
exposures
to
the
test
pesticide
or
structurally
related
compounds
may
interfere
with
study
results.
A
brief
history
should
be
taken
from
each
participant
relating
to
known
prior
exposures
to
pesticides
for
at
least
the
last
2
weeks,
including
reentry
into
potentially
treated
fields.
For
urine
monitoring,
there
should
also
be
a
sufficient
time
period
between
such
exposures
and
participation
in
the
study
to
ensure
adequate
urinary
clearance
of
the
compound
and
its
metabolites,
based
on
pharmacokinetic
data.
This
criterion
was
met.

 
Validated
analytical
methods
for
the
biological
analyte
(
parent
compound
and
its
metabolites)
of
sufficient
sensitivity
are
needed.
Information
on
method
efficiency
and
limit
of
quantitation
(
LOQ)
should
be
provided.
This
criterion
was
met.

 
Samples
should
be
stored
in
a
manner
that
will
minimize
deterioration
and
loss
of
analytes
between
collection
and
analysis.
Biological
monitoring
samples
(
e.
g.,
serum,
plasma
and
urine)
should
be
refrigerated
or
stored
frozen
prior
to
analysis.
Whole
blood
should
not
be
frozen.
Information
on
storage
stability
should
be
provided.
This
criterion
was
met.
The
red
blood
cells
were
washed
with
saline
prior
to
frozen
storage.
It
is
expected
that
lysis
of
the
red
blood
cells
due
to
freezing
would
not
interfere
with
the
red
blood
cell
cholinesterase
testing.

 
Data
should
be
corrected
if
any
appropriate
field
fortified,
laboratory
fortified
or
storage
stability
recovery
is
less
than
90
percent.
This
criterion
was
not
met.
Overall
average
recovery
of
all
field
fortification
samples
was
84%;
however,
the
study
author
excluded
seven
of
the
samples
they
considered
to
be
misfortified
with
recovery
values
<
50%.
This
resulted
in
an
overall
average
recovery
of
103%.

 
Unless
stability
of
the
analyte
has
been
established
prior
to
initiation
of
the
study,
three
samples
of
control
(
nonparticipant)
should
be
fortified
with
two
levels
of
the
biological
analyte
(
parent
or
metabolite(
s),
whichever
is
appropriate)
for
each
experimental
site.
.
This
criterion
was
met.

 
Each
subject's
absorbed
dose
should
be
expressed
in
terms
of
body
weight
using
his/
her
own
measured
value,
and
as
a
cumulative
total
for
each
exposure
period.
The
arithmetic
mean,
range,
standard
deviation,
and
coefficient
of
variation
should
be
calculated
from
the
results
of
all
40
individuals.
Geometric
mean,
range
and
standard
deviation
may
be
calculated
if
the
results
are
shown
to
be
log­
normally
distributed.
Other
distributional
data
should
be
reported,
to
the
extent
possible
(
e.
g.,
percentiles).
These
criteria
were
partially
met.
41
COMPLIANCE
CHECKLIST
Compliance
with
OPPTS
Series
875,
Postapplication
Occupational
and
Residential
Exposure
Test
Guidelines,
Group
B:
Guidelines,
875.2100
(
dislodgeable
foliar
residue
dissipation
­
postapplication)
is
critical.
The
itemized
checklist
below
describes
compliance
with
the
major
technical
aspects
of
OPPTS
875.2100.

875.2100:

 
The
test
substance
must
be
the
typical
end
use
product
of
the
active
ingredient.
This
criterion
was
met.

 
The
production
of
metabolites,
breakdown
products,
or
the
presence
of
contaminants
of
potential
toxicologic
concern,
should
be
considered
on
a
case­
by­
case
basis.
This
criterion
was
partially
met.
The
Study
assayed
for
both
phosmet
and
phosmet
oxon,
however,
no
explanation
was
provided
for
other
possible
breakdown
products.
 
Applications
should
occur
at
the
time
of
season
that
the
end­
use
product
is
normally
applied
to
achieve
intended
pest
control.
This
criterion
was
met.

 
Initiating
testing
immediately
before
a
precipitation
event
should
be
avoided.
This
criterion
was
partially
met.
The
Study
Authors
reported
that
"
examination
of
the
post­
exposure
DFR
results
let
us
to
conclude
that
the
continuing
hard
rain
at
the
end
of
the
exposure
day
had
affected
the
dissipation
kinetics".

 
The
end
use
product
should
be
applied
by
the
application
method
recommended
for
the
crop.
Information
that
verifies
that
the
application
equipment
(
e.
g.,
sprayer)
was
properly
calibrated
should
be
included.
This
criteria
was
met.
The
application
equipment
was
calibrated
and
airblast
application
is
the
recommended
treatment
for
peach
trees.

 
The
application
rate
used
in
the
study
should
be
provided
and
should
be
the
maximum
rate
specified
on
the
label.
However,
monitoring
following
application
at
a
typical
application
rate
is
more
appropriate
in
certain
cases.
This
criterion
was
not
met.
The
label
states
the
maximum
use
rate
is
3.75
lbs.
ai/
acre.
The
test
substance
was
applied
to
the
peach
trees
at
a
rate
of
3
lbs.
ai/
acre.

 
If
multiple
applications
are
made,
the
minimum
allowable
interval
between
applications
should
be
used.
This
criterion
was
met.

 
Dislodgeable
foliar
residue
(
DFR)
data
should
be
collected
from
at
least
three
geographically
distinct
locations
for
each
formulation
and
crop
type.
The
sites
should
be
representative
of
the
regions
(
and
crops)
where
the
chemical
is
used.
This
criterion
was
not
met.
This
study
was
conducted
at
only
one
test
site,
a
peach
orchard
in
Morven,
Georgia.

 
The
site(
s)
treated
should
be
representative
of
reasonable
worst­
case
climatic
conditions
expected
in
intended
use
areas.
Meteorological
conditions
including
temperature,
wind
speed,
daily
rainfall,
and
humidity
should
be
provided
for
the
duration
of
the
study.
This
criterion
was
met.

 
Sampling
should
be
sufficient
to
characterize
the
dissipation
mechanisms
of
the
compound
(
e.
g.,
three
half­
lives
or
35
days
after
the
final
application,
unless
the
compound
has
been
found
to
fully
dissipate
in
less
time;
for
more
persistent
pesticides,
longer
sampling
periods
may
be
necessary).
Sampling
intervals
may
be
relatively
short
in
the
beginning
and
lengthen
as
the
study
progresses.
Background
samples
should
be
collected
before
application
of
the
test
substance
occurs.
This
criteria
was
not
met,
however,
the
purpose
of
collection
DFR
residue
for
this
study
was
to
characterize
the
residue
level
on
the
day
of
reentry,
The
DFR
data
was
not
intended
to
be
used
to
establish
a
dissipation
curve".
42
 
Triplicate,
randomly
collected
samples
should
be
collected
at
each
sampling
interval.
This
criterion
was
met.

 
A
leaf
punch
apparatus
should
be
used
unless
the
nature
of
the
crop
precludes
its
use.
Samples
should
represent
at
least
an
area
of
400
cm2.
This
criterion
was
met.

 
Control
plots
should
be
established
from
which
sufficient
control
samples
can
be
collected.
Control
sites
should
be
upwind
and
a
reasonable
distance
from
the
treatment
site.
This
criterion
may
have
been
met.
The
study
author
reported
that
additional
nontreated
control
samples
were
collected
from
nontreated
orchards;
however,
the
location
of
this
orchard
was
not
specified
in
the
report
and
the
collected
residues
were
not
assayed..

 
Residues
should
be
dislodged
from
leaf
surfaces
using
an
aqueous
surfactant
solution
within
a
reasonable
time
period
(
i.
e.,
EPA
recommends
that
dislodging
occur
within
4
hours).
Dislodging
should
be
repeated
at
least
once
and
the
resultant
solutions
pooled
for
analysis.
This
criterion
was
met.

 
Samples
should
be
stored
in
a
manner
that
will
minimize
deterioration
and
loss
of
analytes
between
collection
and
analysis.
Information
on
storage
stability
should
be
provided.
This
criterion
was
met.

 
Validated
analytical
methods
of
sufficient
sensitivity
are
needed.
Information
on
method
efficiency
(
residue
recovery),
and
limit
of
quantitation
(
LOQ)
should
be
provided.
This
criterion
was
met.

 
Information
on
recovery
samples
must
be
included
in
the
study
report.
A
complete
set
of
field
recoveries
should
consist
of
at
least
one
blank
control
sample
and
three
or
more
each
of
a
lowlevel
and
high­
level
fortification.
These
fortifications
should
be
in
the
range
of
anticipated
residue
levels
in
the
field
study.
This
criterion
was
met.

 
Raw
residue
data
must
be
corrected
if
appropriate
recovery
values
are
less
than
90
percent).
This
criteria
was
met.

 
Dislodgeable
foliar
residues
should
be
reported
as
mg
or
µ
g
per
m2
or
cm2
of
leaf
sampled.
Distributional
data
should
be
reported,
to
the
extent
possible.
This
criterion
was
met.
43
REFERENCES
Mage,
David
T.,
Allen,
R.
H.,
Gondy,
G,
Smith,
W.,
Barr,
D.
B.,
and
L.
Needham.
Estimating
pesticide
dose
from
urinary
pesticide
concentration
data
by
creatinine
correction
in
the
Third
National
Health
and
Nutrition
Examination
Survey
(
NHANES­
III).
(
2004).
JEAEE14:
457­
465.

Tietz,
Norbert
W.
ed.
(
1970).
Fundamentals
of
Clinical
Chemistry,
Philadelphia,
PA:
W.
B.
Saunders
Company.
ISBN
0­
7216­
8865­
9.