    
1
  
21
UNITED
STATES
ENVIRONMENTAL
PROTECTION
AGENCY
WASHINGTON,
D.
C.
20460
OFFICE
OF
PREVENTION,
PESTICIDES
AND
TOXIC
SUBSTANCES
MEMORANDUM
Date:
May
9,
2005
Subj:
Study
Review:
GUTHION
®
50
WP
­
Biological
Monitoring
of
Post­
Application
Workers
During
Manual
Harvesting
of
Walnuts
MRID#:
463164­
05
DP
Barcode:
D307561
PC
Code(
s)
:
058001
From:
Steven
Weiss,
Industrial
Hygienist
Health
Effects
Division/
Reregistration
Branch
3
(
7509C)

Through:
Seyed
Tadayon,
Chemist
Health
Effects
Division/
Reregistration
Branch
3
(
7509C)

To:
Catherine
Eiden,
Chief
Health
Effects
Division/
Reregistration
Branch
3
(
7509C)

Attached
is
a
review
of
the
study
entitled,
GUTHION
®
50
WP
­
Biological
Monitoring
of
Post­
Application
Workers
During
Manual
Harvesting
of
Walnuts.
A
primary
review
of
the
study
was
performed
by
Versar,
Inc.
under
the
supervision
of
HED.
It
has
undergone
secondary
review
in
HED
and
has
been
revised
to
reflect
Agency
policies.
    
2
  
21
STUDY
TYPE:
Biological
and
breathing
zone
air
monitoring
during
postapplication
activities.

TEST
MATERIAL:
Azinphos­
methyl
SYNONYMS:
GUTHION
®
;
S­(
3,4­
dihydro­
4­
oxobenzo[
d]­[
1,2,3]­
trizin­
3­
ylmethyl)
O,
O­
dimethyl
phosphorodithioate;
O,
O­
dimethyl
S­[(
4­
oxo­
1,2,3­
benzotriazin­
3(
4H)­
yl)
methyl]
phosphorodithioate
CITATION:
Study
Author:
D.
R.
Fischer
Title:
GUTHION
®
50
WP
­
Biological
Monitoring
of
Post­
Application
Workers
During
Manual
Harvesting
of
Walnuts
Report
Date:
July
8,
2004
Analytical
Laboratories:
Bayer
CropScience
Environmental
Research
Bayer
Research
Park
17745
South
Metcalf
Avenue
Stilwell,
KS
66085­
9104
Identifying
Codes:
MRID:
463164­
05
Report
No.:
201044
Study
Number:
GU264703
PSI
Number:
RCGUX004
SPONSOR:
Bayer
CropScience
Product
Safety
Management
2
T.
W.
Alexander
Drive
Research
Triangle
Park,
NC
27709
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:
weather
data,
maintenance
chemical
applications,
pesticide
history
data,
irrigation
records,
and
cultural
practices
were
not
collected
under
GLP.
Other
exceptions
included:
(
1)
not
all
data
entries
were
made
promptly,
(
2)
sample
receipt
dates
and
weight
values
were
recorded
into
a
LIMS
system
which
was
not
validated,
(
3)
and
the
bathroom
scale
used
to
weigh
the
workers
was
not
maintained/
calibrated
in
accordance
with
GLP.
The
GLP
statement
also
noted
that
the
storage
containers
of
test
material
were
not
retained
for
the
duration
of
the
study
as
required
due
to
the
nature
of
the
GUTHION
®
50
WP
Solupack
packaging
system.
The
statement
noted
that
none
of
these
exceptions
negatively
impacted
the
integrity
of
the
study.
    
3
  
21
GUIDELINE
OR
PROTOCOL
FOLLOWED:
The
Bayer
CropScience
Protocol
was
provided
in
the
Study
Report
and
included
a
list
of
deviations
from
the
protocol.
The
Study
Report
states
that
the
data
requirements
were
U.
S.
EPA
OPPTS
Harmonized
Test
Guidelines,
Series
875
Occupational
and
Residential
Exposure.

I.
MATERIALS
AND
METHODS
A.
MATERIALS
Formulation:
GUTHION
®
50
WP
­
water
soluble
packets
(
GUTHION
®
Solupak)
EPA
Reg.
No.
264­
733
Lot/
Batch
#
formulation:
3144145
Purity:
The
purity
of
the
batch
was
verified
at
51.69%
azinphos
methyl
with
an
expiration
date
of
May
20,
2005.

CAS
#(
s):
CAS
86­
50­
0
Packaging:
The
product
was
supplied
in
bags
containing
the
water
soluble
packets.

B.
STUDY
DESIGN
There
were
6
amendments
to
the
protocol
and
8
deviations
from
the
protocol.
The
amendments
included:

(
1)
A
statement
was
added
to
the
protocol
indicating
that
the
workers
participating
in
the
study
will
have
had
experience
harvesting
walnuts.
(
2)
An
explanation
was
added
to
the
protocol
for
the
use
of
MSMB
as
a
urinary
biomarker
for
azinphos­
methyl.
(
3)
A
statement
was
added
to
the
protocol
indicating
that
the
type
of
clothing
worn
by
the
workers
will
be
documented.
(
4)
Additional
information
was
added
to
the
protocol
regarding
the
packing
and
storing
conditions
for
the
blood
samples.
(
5)
The
additive
`
NIS'
which
will
be
used
during
application
was
further
defined
(`
NIS'
stands
for
non­
ionic
surfactant).
(
6)
The
­
3,
­
1,
and
4
day
time
point
blood
samples
will
be
shipped
via
two
overnight
express
carriers
to
increase
the
probability
of
safe
receipt
of
the
samples
at
the
laboratory
for
cholinesterase
testing
within
the
required
time
from
sample
collection.

These
deviations
included:
(
1)
At
times
during
collection,
the
urine
samples
were
maintained
cold
using
a
freezer
rather
than
    
4
  
21
a
refrigerator.
Also,
only
limited
temperature
data
were
available
for
the
urine
samples
during
collection.
Each
refrigerator
and
freezer
was
equipped
with
a
Hobo
temperature
recorder,
but
some
of
the
Hobo
units
did
not
operate
properly
due
to
a
problem
during
launch
of
the
units.
In
addition,
the
urine
sample
storage
temperatures
may
have
occasionally
been
below
freezing.
Field
fortification
samples,
stored
with
the
field
samples,
were
used
to
monitor
the
stability
of
the
analytes
of
interest
during
storage,
collection,
and
shipping.
Also,
while
subsampling
the
bulk
urine
samples,
the
bulk
containers
were
maintained
in
coolers
with
frozen
gel
packs
(
rather
than
refrigerators)
to
keep
the
samples
cool,
and
temperature
data
were
not
recorded
for
the
samples
during
this
period
of
time.
(
2)
The
data
and
time
for
transfer
of
the
control
and
fortified
urine
samples
from
the
freezer
to
the
refrigerators
used
for
storing
the
workers'
urine
samples
during
collection
was
recorded
on
paper,
but
not
in
FieldNotes.
(
3)
Following
collection,
the
OVS
tube
samples
from
the
workers
were
not
placed
directly
into
a
freezer,
but
were
maintained
on
dry
ice
until
storage
in
a
freezer.
The
samples
were
maintained
in
a
frozen
condition
at
all
times,
since
dry
ice
was
always
present
with
the
samples.
(
4)
Additional
information
was
given
for
the
analysis
of
the
duplicate
blood
samples
described
in
a
protocol
amendment.
Upon
successful
receipt
and
analysis
of
one
set
of
the
duplicate
blood
samples,
the
second
set
was
discarded.
(
5)
The
protocol
indicated
that
sweeping/
vacuuming
would
be
one
of
the
tasks
for
which
biomonitoring
would
be
conducted.
Biomonitoring
was
conducted
for
the
sweeping
activity,
but
not
conducted
for
the
vacuuming
activity.
Vacuuming
usually
takes
much
less
time
than
the
shaking,
raking,
and
sweeping
activities
and
so
was
not
included
as
part
of
the
study.
(
6)
Other
than
during
agricultural
harvest,
the
activities
of
the
workers
were
not
recorded
during
the
sample
collection
period
as
required
int
the
protocol.
However,
the
workers
were
sequestered
during
the
sample
collection
period,
and
the
activities
of
the
workers
were
monitored
to
insure
that
they
followed
the
study
procedures
and
did
not
receive
any
exposure
to
other
pesticides.
(
7)
Each
worker
individually
chose
and
wore
clothing
typical
of
that
they
normally
wore
when
working.
This
clothing
may
not
have
necessarily
been
`
single
layer'
as
stated
in
the
protocol
or
`
long
sleeves'
or
`
sleeves
not
rolled
up'
as
stated
in
the
AHETF
Worker
Clothing
Acceptability
Criteria
document.
All
aspects
of
this
study
were
conducted
in
accordance
with
the
Guthion
Solupak
(
GUTHION
50WP)
label
(
application
rates,
application
intervals,
re­
entry
intervals,
etc
were
followed)
and
the
Worker
Protection
Standard
40
CFR
part
170.
The
objective
was
to
conduct
the
study
as
close
as
possible
to
normal
agricultural
and
worker
practice
to
give
the
most
realistic
measurement
of
the
exposure
that
workers
may
receive
while
harvesting
walnuts
in
an
area
treated
with
GUTHION
50
WP.
(
8)
To
increase
the
probability
of
having
15
worker
participants
available
for
the
day
of
harvest
control
urine
and
blood
samples
were
collected
from
two
additional
workers
up
until
beginning
harvest.
Since
15
workers
were
available
at
the
time
of
harvest,
the
extra
workers
were
not
needed
and
were
released
from
the
study
just
prior
to
the
start
of
harvest.

These
deviations
from
the
protocol
were
reported
to
not
have
any
adverse
effects
on
the
study.

1.
Test
Site:
The
test
site
was
a
single
walnut
tree
grove
plot
located
near
Poplar,
California
in
Tulare
County
(
EPA
Region
10).
For
the
trial,
23.6
acres
of
walnut
trees
were
dedicated
to
the
reentry
monitoring
events.
The
maintenance
chemicals
applied
during
the
growing
season
included
Roundup,
Basic
Copper,
Kocide
20/
20,
Lorsban
4E,
and
Omite
30WS.
Except
for
Lorsban
4E,
none
of
these
maintenance
chemicals
are
organophosphate
or
carbamate
pesticides.
Lorsban
4E,
an
organophosphate
pesticide,
was
applied
on
7/
8/
03
and
on
8/
20/
03
(
41
days
prior
to
reentry
    
5
  
21
activities).
Typical
cultural
and
irrigation
practices
were
employed
at
the
site.

The
variety
of
walnuts
used
was
Serr.
The
distance
between
rows
and
trees
within
a
row
was
reported
to
be
25
feet.
The
approximate
density
was
69
trees/
A.

2.
Meteorology:
Meteorological
conditions
were
recorded
during
the
application.
This
information
is
provided
in
Table
1.
The
Study
Report
also
noted
that
rainfall
between
the
first
application
and
the
reentry
activity
was
0.17
inches.
There
was
no
irrigation
applied
between
the
application
and
reentry
activity.

Table
1.
Meteorological
Conditions
During
Application
on
9/
30/
04
Air
Temp
74
F
Wind
Speed
(
mph)
0
to
1.6
Wind
Direction
NW
Percent
Cloud
Cover
0
Rainfall
Within
24
Hours
of
Application
(
inches)
None
3.
Number
and
type
of
workers:
Fifteen
male
workers
were
monitored
for
this
study.
The
Study
Report
stated
that
all
participants
were
experienced
agricultural
workers
who
had
recently
been
harvesting
walnuts.
The
Study
Report
also
stated
that
the
workers
were
not
exposed
to
azinphos­
methyl
or
any
other
organophosphate
or
carbamate
chemicals
for
at
least
10
days
prior
to
harvest.
The
workers
ranged
in
age
from
18
years
to
35
years.
The
weight
of
the
workers
ranged
from
56.7
kg
to
108
kg.
The
workers'
years
of
experience
ranged
from
0.5
years
to
>
10
years.

Two
spare
workers
were
added
to
the
study
on
the
day
before
reentry
to
increase
the
probability
of
15
workers
being
available
on
the
day
of
reentry.
These
workers
were
ultimately
not
used,
as
15
workers
were
available
on
the
day
of
reentry.

4.
Replicates:
Harvesting
activities
took
place
30
days
after
the
airblast
application
of
2.01
lb
ai/
A
of
azinphosmethyl
to
the
test
site.
The
workers
harvested
walnuts
from
the
designated
trees
in
the
treated
plot
for
8
hours
(
including
breaks).
The
workers
entered
the
grove
at
the
same
time
(
7:
30
AM),
took
a
30
minute
lunch
break
and
two
15
minute
breaks,
and
ended
the
work
day
at
the
same
time
(
3:
30
PM).
Table
6
of
the
Study
Report
provides
observations
of
the
workers
recorded
during
the
study.

Workers
1
and
2
(
called
`
shakers')
operated
the
two
shaker
machines
used
during
the
reentry
activity.
The
shaker
machine
was
a
3­
wheeled
unit
that
had
a
set
of
large
pinchers
attached
to
a
hydraulic
arm.
After
the
shaker
machine
was
driven
in
position
near
a
tree,
the
pinchers
were
affixed
to
the
trunk
or
a
major
limb
of
the
tree
and
used
to
rapidly
shake
the
tree
for
    
6
  
21
approximately
10
seconds,
causing
the
walnuts
(
and
also
small
tree
limbs)
to
fall
from
the
tree.
The
shaker
machine
was
driven
from
tree
to
tree,
while
alternating
back­
and­
forth
between
two
tree
rows.
While
operating
the
shaker
machines,
the
workers
were
enclosed
within
a
cab.

Workers
3
and
4
(
called
`
sweepers')
operated
the
two
sweeper
machines
used
during
the
reentry
activity.
The
sweeper
machine
was
a
3­
wheeled
unit
with
a
large
brush
roller
in
front
that
was
angled
slightly
to
the
right
side
of
the
unit.
As
the
sweeper
machine
was
driven
between
the
tree
rows,
the
fallen
walnuts
(
and
also
small
tree
limbs)
were
swept
from
one
half
of
the
row
into
the
center
of
the
row
by
the
rotating
brush.
During
the
return
pass
on
that
same
row,
the
walnuts
on
the
other
half
of
the
row
were
also
swept
into
the
center,
leaving
a
single
windrow
in
the
center
of
the
row.
The
sweeper
machine
was
also
equipped
with
a
blower
on
the
left
side
of
the
unit
that
was
used
to
blow
the
walnuts
on
the
berms
of
the
tree
rows
into
the
neighbouring
row
as
the
unit
proceeded
down
the
row.
The
workers
were
not
enclosed
within
a
cab
while
operating
the
sweeper
machines.

Workers
5
to
15
(
called
`
rakers')
used
rakes
and
also
their
hands
to
move
small
tree
limbs
from
the
rows
prior
to
sweeper
machine
driving
down
the
row.
Tree
limbs
were
also
removed
from
the
windrow
and
placed
on
the
berms
of
the
tree
rows.
Using
rakes,
these
workers
moved
walnuts
near
the
trunks
of
the
trees
that
were
not
blown
by
the
sweeper
machine,
so
that
these
walnuts
could
subsequently
be
swept
into
a
windrow
by
the
sweeper
machine.

5.
Protective
clothing:
The
Study
Report
states
that
the
workers
wore
clothing
typical
of
what
they
would
normally
wear
when
performing
agricultural
work.
The
workers
clothing
was
listed
in
Table
6
of
the
Study
Report,
and
typically
included
long
sleeve
shirts
and
long
work
pants.
One
worker
wore
a
short
sleeve
shirt
and
two
workers
wore
a
short
sleeve
shirt
underneath
a
long
sleeve
shirt.
Each
worker
wore
a
hat,
plastic
hair
cover,
or
bandana
on
the
head,
except
for
one
worker
who
did
not
wear
any
head
protection.
Type
N95
dust
masks
were
made
available
to
each
worker
just
prior
to
beginning
harvest
and
each
worker
was
allowed
to
make
their
own
decision
regarding
the
use
of
a
mask.
All
workers
wore
a
dust
mask;
however,
the
mask
was
not
necessarily
worn
for
the
entire
exposure
period.

6.
Application
Method
and
Rate:

Application
rate(
s):
A
single
foliar
application
was
made
at
2.01
lb
ai/
A
on
September
30,
2003.

Application
Equipment:
Application
was
made
with
a
tractor­
drawn
Air­
O­
Fan
airblast
sprayer,
Model
GB
36.
Five
nozzles
were
located
on
one
side
of
the
sprayer.
The
sprayer
had
a
500­
gallon
tank.

Spray
Volume:
The
actual
spray
volume
was
reported
as
202
gal/
A.
According
to
the
product
label,
the
test
substance
should
be
applied
in
a
maximum
spray
volume
of
400
gal/
A.

Equipment
Calibration:
The
authors
reported
that
the
sprayers
were
calibrated
prior
to
the
application.

7.
Exposure
monitoring
methodology:
    
7
  
21
Urine
Samples
Total
urine
output
was
collected
from
each
worker
during
each
24­
hour
period
starting
1
day
prior
to
reentry
through
4
days
after
reentry.
Day
­
1
samples
were
those
collected
starting
after
the
first
void
of
the
bladder
in
the
morning
on
the
day
prior
to
reentry
and
ending
after
the
first
void
on
the
day
of
reentry.
Day
0
samples
were
those
collected
during
the
24­
hour
period
starting
when
the
workers
began
the
reentry
activities.
Samples
were
collected
in
individually
labeled
4­
L
Urisafe
®
bulk
containers.
Samples
were
kept
in
refrigerators
during
the
24­
hour
collection
time,
except
for
the
Day
0
samples
which
were
kept
cool
using
a
freezer
powered
by
a
portable
generator.
After
collection
of
each
24­
hour
bulk
sample,
the
total
volume
of
each
sample
was
recorded.
The
samples
were
mixed
by
shaking,
and
duplicate
25­
mL
aliquots
were
transferred
to
90­
mL
urine
specimen
containers.
The
bulk
samples
and
aliquots
were
kept
frozen
and
the
aliquots
were
shipped
frozen
to
Bayer
Research
Park.
The
bulk
samples
were
kept
frozen
until
notification
by
Bayer,
at
which
time
they
were
discarded.

Blood
Samples
Blood
samples
were
collected
from
each
worker
at
the
following
time
intervals:
(
1)
3
days
prior
to
reentry,
(
2)
1
day
prior
to
reentry;
and
(
3)
on
the
day
of
reentry
after
a
full
work
day,
and
(
4)
4
days
following
reentry.
The
control
samples
collected
3
days
and
1
day
prior
to
the
reentry
activity
for
each
worker
were
used
to
establish
baseline
cholinesterase
activity.
The
samples
were
collected
into
individually
labelled
collection
tubes
containing
EDTA
K3
as
an
additive.
Prior
to
sample
collection,
the
skin
was
thoroughly
cleaned
to
eliminate
possible
contamination
of
pesticide
residue
that
may
have
been
on
the
skin.
Blood
samples
were
packaged
in
compliance
with
International
Air
Transport
Association
Packaging
Instructions
650
and
were
maintained
cool
during
transport
in
a
styrofoam
cooler
containing
frozen
gel
packs.
Samples
were
shipped
to
Bayer
Research
Park
on
the
day
of
collection.

Breathing
Zone
Air
Samples
Breathing
zone
air
samples
were
taken
using
OVS
tubes,
containing
XAD­
2
sorbent,
and
a
personal
air­
sampling
pump
attached
to
the
worker's
belt.
The
OVS
tubes
consisted
of
a
glass
fiber
filter,
secured
with
a
Teflon
®
holding
ring,
covering
a
270
mg
layer
of
XAD­
2
sorbent
in
the
top,
primary
bed
and
a
140
mg
layer
of
XAD­
2
sorbent
in
the
bottom,
backup
bed.
The
OVS
tube
was
connected
to
the
pump
using
Tygon
®
tubing
and
clipped
onto
the
worker's
outer
clothing,
with
the
inlet
positioned
in
the
breathing
zone
of
the
worker.
The
air
samples
were
collected
by
operating
the
pumps
over
the
entire
workday
(
including
breaks).
Just
prior
to
monitoring
the
reentry
activity,
the
air
sampling
pumps
were
calibrated
at
a
rate
of
approximately
2
L/
min.
The
pump
flow
rates
were
collected
before
and
after
the
monitoring
period
and
the
pumps
were
checked
throughout
the
monitoring
period
to
ensure
continual
operation.
At
the
end
of
the
work
day,
the
OVS
tube
was
disconnected
and
caps
were
fitted
onto
the
ends.
A
label
was
placed
on
the
tube,
which
was
placed
into
a
pre­
labeled
plastic
bag.
The
samples
were
stored
and
then
shipped
frozen
to
Bayer
Research
Park.

C.
ANALYTICAL
METHODOLOGY:

1.
Sample
Extraction/
Detection:

Urine
Samples
Extraction
method:
0.100
mL
of
[
2H3]
MSMB
internal
standard
solution
(
0.300
µ
g/
mL)
was
added
to
a
10
mL
    
8
  
21
aliquot
of
urine.
The
sample
was
added
to
a
10
mL
Chem
Elut
cartridge
and
the
cartridge
was
eluted
with
three
20
mL
portions
of
methylene
chloride
into
a
60
mL
vial.
A
TurboVap
was
used
to
evaporate
the
methylene
chloride
at
35C
for
45
minutes.
The
residue
was
dissolved
in
0.10
mL
of
methanol,
a
0.9
mL
aliquot
of
0.1%
formic
acid
was
added
and
the
sample
was
mixed.
An
aliquot
of
the
sample
was
then
analyzed
using
high
pressure
liquid
chromatography­
triple
stage
quadrupole
mass
spectrometry.

The
method
for
urine
creatinine
analysis
was
reported
to
be
based
on
the
Jaffe/
Alkaline
Picrate/
Kinetic
method.

Detection
methods:
See
Table
2.

Table
2.
Summary
of
HPLC
and
MS
Conditions
for
Urine
HPLC
Conditions
GC
Column:
Zorbax
SB
Aq,
5
µ
m,
50
mm
x
2.1
mm
Solvents:
0.1%
aqueous
formic
acid
(
solvent
A)
and
methanol
(
solvent
B)
Solvent
Program:
Time
(
min)
Solvent
A(%)
Solvent
B(%)
Flow
(
mL/
min)
Initial
68
32
0.200
2.5
68
32
0.200
2.85
15
85
0.200
2.90
68
32
0.300
5.00
68
32
0.300
5.05
68
32
0.200
Injection
Volume:
Autosampler
with
a
20
µ
L
loop
MS
Conditions
Collision
cell
pressure:
1.5
mTorr
Spray
Voltage:
1900
kV
Capillary
temperature:
390C
Sheath:
90
psi
Auxilary
gas:
20
Ionization
mode:
Positive
ion
Divert
valve:
On
from
0.60
minutes
to
2.60
minutes
(
HPLC
effluent
enters
the
LC/
MS)

Instrument
performance
and
calibration:
Calibration
curves
were
prepared
for
each
calibration
run.
The
relative
response
of
the
detector
in
the
lc/
ms­
ms
chromatographic
system
to
MSMB
in
solvent
was
linear
over
the
range
of
0.05
ng/
mL
to
10
ng/
mL.
The
correlation
of
coefficients
were
all
>
99%.
The
limit
of
quantitation
(
LOQ)
for
urine
samples
was
reported
to
be
0.10
ng/
mL
of
MSMB.
The
limit
of
detection
(
LOD)
for
the
urine
samples
was
reported
to
be
0.08
ng/
mL.

Quantification:
The
MSMB
residue
level
in
urine
was
determined
by
comparing
the
LC/
MS
measurement
of
MSMB
to
the
measurement
of
the
MSMB
internal
standard.

Blood
Samples
    
9
  
21
Extraction/
Detection
method:
Blood
samples
were
analyzed
for
plasma
and
red
blood
cell
cholinesterase
activity.
The
method
was
reported
to
be
a
modification
of
the
method
described
by
Ellman
(
Ellman,
M.
L.,
K.
D.
Cortney,
V.
Andres,
and
R.
M.
Featherston.
1961.
A
New
and
Rapid
Colorimetric
Determination
of
Acetylcholinesterase
Activity.
Biochemical
Pharmocology
7:
88­
95).

Breathing
Zone
Air
Samples
Extraction
method:
The
top
and
bottom
sections
of
the
OVS
tubes
were
analyzed
separately.
The
top
portion
of
the
OVS
tube
(
including
the
Teflon
®
ring,
filter,
upper
layer
of
XAD­
2
resin,
and
the
upper
foam
ring)
was
disassembled
and
placed
into
a
labeled
40
mL
vial.
The
bottom
portion
of
the
OVS
tube
(
lower
layer
of
XAD­
2
resin
and
lower
foam
plug)
was
disassembled
and
placed
into
a
separate,
labeled
40
mL
vial.
Each
sample
received
10
mL
of
acetonitrile
and
0.100
mL
of
an
internal
standard
solution,
which
contained
a
mixture
of
[
2H6]
azinphos­
methyl
(
10.0
µ
g/
mL)
and
[
2H6]
azinphos­
methyl
oxon
(
2.0
µ
g/
mL).
Each
sample
was
then
sonicated
for
2
minutes
and
a
0.25
mL
aliquot
was
removed
and
diluted
with
0.75
mL
of
water.
The
diluted
samples
were
analyzed
by
high
pressure
liquid
chromatography­
triple
stage
quadrupole
mass
spectrometry.

Detection
methods:
See
Table
3
Table
3.
Summary
of
HPLC
and
MS
Conditions
for
Breathing
Zone
Air
Samples
HPLC
Conditions
GC
Column
Xterra
MS
C18,
3.5
µ
m,
50
mm
x
4.6
mm
Solvents
0.1%
aqueous
formic
acid
(
solvent
A)
and
methanol
(
solvent
B)
Solvent
Program
Isocratic
at
38%
Solvent
A
and
62%
Solvent
B
Flow
Rate
1.00
mL/
min
Injection
Volume
Autosampler
with
a
20
µ
L
loop
MS
Conditions
Instrument
Setup
LC­
MS/
MS
with
electrospray
interface
and
1:
4
split
Collision
cell
pressure
1.5
m
Torr
Spray
voltage
5.900
kV
Capillary
temperature
235C
Sheath
gas
100
psi
Auxiliary
gas
30
Ionization
mode
Positive
ion
Divert
valve
On
from
0.5
min
to
2.50
min
(
HPLC
effluent
enters
LC/
MS)

Instrument
performance
and
calibration:
Calibration
curves
were
prepared
for
each
calibration
run.
The
relative
response
of
the
detector
in
the
lc/
ms­
ms
chromatographic
system
to
MSMB
in
solvent
was
linear
over
the
range
of
30
ng
to
30,000
ng.
The
correlation
of
coefficients
were
all
>
99%.
The
limit
of
quantitation
for
both
azinphos­
methyl
and
azinphos­
methyl
oxon
was
reported
to
be
100
ng.
The
limit
of
detection
for
azinphos­
methyl
and
azinphos­
methyl
oxon
were
reported
as
5
ng
and
9
ng,
respectively.
    
10
  
21
Quantification:
The
azinphos­
methyl
or
azinphos­
methyl
oxon
residue
level
in
the
air
samples
was
determined
by
comparing
the
LC/
MS
measurement
of
azinphos­
methyl
or
azinphos­
methyl
oxon
to
the
measurement
of
the
azinphos­
methyl
or
azinphos­
methyl
oxon
internal
standard.

2.
Quality
Control:

Lab
Recovery:
Concurrent
laboratory
recoveries
were
performed
for
both
urine
samples
and
for
the
inhalation
exposure
analysis.
Urine
samples
were
fortified
at
the
0.50
ng/
mL
level
and
OVS
tubes
were
fortified
at
the
0.50
ng
level.
The
results
provided
in
the
Study
Report
were
verified
and
these
are
presented
in
Tables
4
and
5.
The
recoveries
were
corrected
for
residues
found
in
blank
samples.

Table
4.
Urine
Sample
Concurrent
Laboratory
Recoveries
a
Sample
No.
Fortification
Level
(
ng/
mL)
Measured
residue
(
ng/
mL)
Average
Blank
Sample
Residue
(
ng/
mL)
Corrected
residue
b
(
ng/
mL)
Recovery
(%)
Average
Recovery
(%)

0.5
0.495
0.466
93
GUO18­
03D­
1H
0.5
0.477
0.029
0.448
90
91
0.5
0.476
0.4625
93
GUO18­
03D+
0H
0.5
0.506
0.0135
0.4925
99
96
0.5
0.45
0.4315
86
GUO18­
03D+
1H
0.5
0.504
0.0185
0.4855
97
92
0.5
0.527
0.5185
104
GUO18­
03D+
2H
0.5
0.46
0.0085
0.4515
90
9
0.5
0.438
0.4305
86
GUO18­
03D+
3H
0.5
0.507
0.0075
0.4995
100
93
0.5
0.527
0.516
103
GUO18­
03D+
4H
0.5
0.567
0.011
0.556
111
107
a
Recoveries
calculated
using
raw
data
provided
in
Appendix
3
of
the
Study
Report.
b
Corrected
residue
is
the
measured
residue
minus
the
average
blank
residue.

Table
5.
OVS
Tubes
Concurrent
Laboratory
Recoveries
a
Analyte
Fortificatio
n
Level
(
ng)
Measured
Bottom
Residue
(
ng)
Bottom
Blank
Residues
(
ng)
Corrected
Bottom
Residue
b
(
ng)
Measured
Top
Residue
(
ng)
Top
Blank
Residues
(
ng)
Corrected
Top
Residue
(
ng)
Total
Residue
(
top
+
bottom)
(
ng)
Percent
recovery
(%)

AZM
c
500
12.1
17.5
­
5.4e
417.8
17.5
400.3
402.8
81
AZMoxon
d
500
4.5f
4.5f
0e
510.2
4.5f
505.7
510.2
102
a
Recoveries
calculated
using
raw
data
provided
in
Appendix
3
of
the
Study
Report.
    
11
  
21
b
Corrected
residue
is
the
measured
residue
minus
the
average
blank
residue.
c
AZM
=
azinphos­
methyl
d
AZM­
oxon
=
azinphos­
methyl
oxon
e
Since
the
corrected
bottom
residue
was
less
than
the
LOD,
½
the
LOD
was
used
in
subsequent
calculations.
f
Residues
<
LOD
are
shown
as
1/
2
LOD.
    
12
  
21
Field
recovery:

Urine
Samples
Field
fortification
samples
were
prepared
at
0.50
ng/
mL
and
10.0
ng/
mL
for
urine
samples.
The
fortification
samples
were
prepared
from
two
200
mL
aliquots
of
control
urine.
One
aliquot
received
0.1
mL
of
a
1.00
µ
g/
mL
fortification
solution,
while
the
other
received
two
mL
of
the
fortification
solution.
The
solutions
were
then
mixed
well
and
three
50
mL
aliquots
were
removed
and
placed
in
separate
containers.
A
summary
of
the
results
were
verified
and
are
provided
in
Table
6.
The
recoveries
were
corrected
for
residues
found
in
blank
samples.
The
average
low
level
fortification
recovery
was
106%
and
the
average
high
level
fortification
recovery
was
96%.

Table
6.
Urine
Sample
Field
Fortification
Recoveries
a
Fortification
Level
(
ng/
mL)
Measured
residue
(
ng/
mL)
Blank
Samples
(
ng/
mL)
Corrected
residue
b
(
ng/
mL)
Recovery
(%)
Average
Percent
recovery
(%)

0.471
0
0.471
94
0.537
0
0.537
107
Low
fortification
level
0.5
0.579
0
0.579
116
106
9.356
0
9.356
94
9.367
0
9.367
94
High
fortification
level
10
10.138
0
10.138
101
96
a
Recoveries
calculated
using
raw
data
provided
in
Appendix
3
of
the
Study
Report.
b
Corrected
residue
is
the
measured
residue
minus
the
average
blank
residue.
Breathing
Zone
Air
Samples
Field
fortification
samples
were
prepared
at
500
ng
and
10,000
ng
for
OVS
tubes.
0.050
mL
of
a
fortification
solution
containing
10
µ
g/
mL
azinphos­
methyl
and
10
µ
g/
mL
azinphos­
methyl
oxon
were
added
to
blank
laboratory
control
OVS
tubes
for
the
low
field
fortification
samples.
0.050
mL
of
a
fortification
solution
containing
200
µ
g/
mL
azinphos­
methyl
and
200
µ
g/
mL
azinphosmethyl
oxon
were
added
to
blank
laboratory
control
OVS
tubes
for
the
high
field
fortification
samples.
Air
was
then
drawn
through
the
tubes
for
10
minutes
at
a
rate
of
3
mL/
min
to
evaporate
the
solvent.
The
tubes
were
then
capped
and
labeled.
The
results
provided
in
the
Study
Report
were
verified
and
are
presented
in
Table
7.
The
recoveries
were
corrected
for
residues
found
in
blank
samples.
For
azinphos­
methyl,
the
average
low
level
fortification
recovery
was
96%
and
the
average
high
level
fortification
recovery
was
99%.
For
azinphos­
methyl
oxon,
the
average
low
level
fortification
recovery
was
113%
and
the
average
high
level
fortification
recovery
was
101%.
    
13
  
21
Table
7.
OVS
Tubes
Field
Fortification
Recoveries
a
Analyte
Fortificatio
n
Level
(
ng/
mL)
Measure
d
Bottom
Residue
(
ng)
Bottom
Blank
Residue
s
(
ng)
Correcte
d
Bottom
Residue
(
ng)
Measured
Top
Residue
(
ng)
Top
Blank
Residue
s
(
ng)
Correcte
d
Top
Residue
b
(
ng)
Total
Residue
(
top
+
bottom)
(
ng)
Recovery
(%)
Overall
Average
Recovery
(%)

2.5
f
­
7.5
e
515
21.4
494
497
99
5
­
2.5
e
516
21.4
494.8
497
99
500
2.5
f
­
7.5
e
470
21.4
448.9
451
90
96
16.7
9.2
10,516
21.4
10494.3
10,504
105
2.5
f
­
7.5
e
8,995
21.4
8973.8
8,976
90
AZM
c
10,000
2.5
f
7.5
­
7.5
e
10,104
21.4
10082.9
10,085
101
99
4.5
f
0
e
562
4.5
f
557.7
562
112
4.5
f
0
e
562
4.5
f
557.6
562
112
500
4.5
f
0
e
576
4.5
f
571.6
576
115
113
4.5
f
0
e
10,282
4.5
f
10277.2
10,282
103
4.5
f
0
e
10,170
4.5
f
10165.2
10,170
102
AZMoxon
d
10000
4.5
f
4.5
f
0
e
9,845
4.5
f
9840.8
9,845
98
101
a
Recoveries
calculated
using
raw
data
provided
in
Appendix
3
of
the
Study
Report.
b
Corrected
residue
is
the
measured
residue
minus
the
average
blank
residue.
c
AZM
=
azinphos­
methyl
d
AZM­
oxon
=
azinphos­
methyl
oxon
e
Since
the
corrected
bottom
residue
was
less
than
the
LOD,
½
the
LOD
was
used
in
subsequent
calculations.
f
Residues
<
LOD
are
shown
as
1/
2
LOD.

Tank
mix:
No
information
on
tank
mix
analysis
was
provided
in
the
Study
Report.

Travel
Recovery:
Travel
recovery
was
not
assessed
in
the
Study
Report.

Storage
Stability:
All
samples
were
stored
frozen
prior
to
analysis.
Urine
samples
were
held
for
a
maximum
of
3
months
(
89
days)
prior
to
extraction
and
all
extracts
were
analyzed
within
3
days
after
extraction.
OVS
tube
samples
were
held
for
a
maximum
of
2.8
months
(
83
days)
prior
to
extraction
and
all
extracts
were
analyzed
within
1
day
after
extraction.
The
Study
Report
states
that
the
acceptable
recoveries
from
the
field
fortification
samples
indicate
that
the
field
samples
would
be
stable
over
the
period
of
collection,
storage,
and
shipping
through
sample
analysis.
A
separate
storage
stability
study
was
not
performed.

II.
RESULTS
AND
CALCULATIONS:

A.
EXPOSURE
CALCULATIONS:

Internal
Dose
The
AZM
dose
estimates
calculated
from
urinary
MSMB
residues
in
this
study
represent
the
internal
exposure.
The
worker
replicates
wore
dust/
mist
respirators
during
all/
most
of
the
exposure
period.
Therefore,
dose
estimates
may
underestimate
exposure
via
the
inhalation
route.
    
14
  
21
Using
the
raw
data
provided
in
the
Study
Report,
azinphos­
methyl
internal
dose
estimates
in
mg/
kg
body
weight
were
calculated
for
each
worker
and
each
worker
type
by
sampling
interval
and
as
a
cumulative
total
over
the
4
sampling
days
(
120
hrs).
The
results
corrected
for
background
(
day
­
1)
residue.
The
background
residues
were
<
LOD
in
eleven
of
the
workers
and
ranged
from
0.0945
to
0.358
ng/
mL
in
four
workers
(
Nos.
4,
5,
8,
and
15).
The
measured
residues
were
corrected
to
100%
recovery
based
on
recoveries
of
the
associated
field
fortification
samples.
Residues
<
LOD
were
set
to
1/
2
LOD
for
all
calculations.
The
measured
residues
were
adjusted
for
the
volume
of
urine
collected
and
the
internal
dose
was
calculated
by
adjusting
the
MSMB
excreted
during
each
sampling
interval
for
the
cumulative
percent
of
the
absorbed
dose
excreted
120
hours
after
exposure
(
as
determined
from
a
previous
study
 
86.3%)
and
the
percent
of
the
urine
activity
attributed
to
MSMB
(
determined
from
a
previous
study
­­
9.2%).

The
internal
azinphos­
methyl
dose
was
determined
from
the
residues
measured
in
24
hour
urine
samples
collected
from
each
worker
for
the
time
period
of
120
hours
after
reentry
(
5
days,
including
the
day
of
reentry)
.
MSMB
residue
levels
are
presented
in
this
report
as
µ
g
equivalents
of
parent
azinphos
methyl.
Equivalents
were
calculated
using
a
molecular
weight
conversion
factor
of
1.328.
The
total
MSMB
excreted
for
each
worker
over
the
120
hour
sampling
period
following
exposure
to
arrive
at
an
estimated
dose.
Table
8
provides
the
azinphos­
methyl
dose
(
over
120
hrs)
for
shakers,
sweepers,
and
rakers
based
on
mg
per
kg
body
weight.
The
total
average
azinphos­
methyl
doses
for
shakers,
sweepers,
and
rakers
(
with
background
correction)
are
0.00019,
0.00034,
and
0.00089
mg/
kg
body
weight,
respectively.
Table
9
provides
individual
daily
residue
values
and
total
azinphos­
methyl
doses
for
each
worker.

Breathing
Zone
Air
Samples
Air
samples
were
collected
in
the
breathing
zone
of
workers
using
OVS
sampling
tubes.
Residues
of
both
azinphos­
methyl
and
azinphos­
methyl
oxon
were
measured
on
the
top
and
bottom
portions
of
the
sampling
tubes
and
combined
for
a
total
azinphos­
methyl
residue.

All
field
samples
were
adjusted
for
field
fortification
recoveries.
Residues
that
were
reported
as
<
LOD
were
included
in
calculations
as
½
LOD.
The
inhalation
exposure
concentration
for
shakers
averaged
2.2
µ
g/
m3,
2.8
µ
g/
m3
for
sweepers,
and
8.6
µ
g/
m3
for
all
rakers.

Cholinesterase
Activity
Cholinesterase
activity
(
both
plasma
and
red
blood
cells)
was
monitored
through
blood
sampling
prior
to
reentry
(
on
days
­
3
and
­
1),
on
day
0
(
immediately
following
reentry)
and
day
4.
The
depression
of
cholinesterase
activity
was
then
determined
by
comparing
the
background
activity
to
the
activity
measured
on
days
0
and
4.
These
results
are
provided
in
Table
12.
The
percent
decrease
in
plasma
cholinesterase
on
day
0
ranged
from
­
1.7%
to
18.4%
for
shakers,
1.80%
to
3.25%
for
sweepers,
and
0.91%
to
10.47%
for
rakers.
The
percent
decrease
in
plasma
cholinesterase
on
day
4
ranged
from
­
11.73%
to
3.46%
for
shakers,
1.53%
to
2.17%
for
sweepers,
and
­
9.98%
to
7.41%
for
rakers.
The
percent
decrease
in
red
blood
cell
cholinesterase
on
day
0
ranged
from
2.91%
to
4.20%
for
shakers,
­
2.08%
to
4.18%
for
sweepers,
and
­
5.05%
to
8.69%
for
rakers.
The
percent
decrease
in
red
blood
cell
cholinesterase
on
day
4
ranged
from
­
0.352%
to
­
1.56%
for
shakers,
­
0.39%
to
2.84%
for
sweepers,
and
­
2.33%
to
5.89%
for
rakers.

The
average
percent
change
in
plasma
cholinesterase
(
ChE)
immediately
following
the
day
of
    
15
  
21
entry
was
negative
five
percent
with
a
range
of
±
5
percent.
One
worker
(
out
of
15)
experienced
an
18
percent
drop
in
plasma
ChE
levels.
The
data
indicate
that
by
day
4
following
exposure,
the
average
plasma
ChE
levels
returned
to
baseline
levels
with
average
plasma
ChE
change
at
positive
one
percent
with
a
range
of
±
five
percent.
The
average
percent
change
in
red
blood
cell
(
RBC)
cholinesterase
levels
immediately
following
the
day
entry
was
negative
two
percent
with
a
range
of
±
4
percent.
That
remained
about
constant
on
day
4.

III
DISCUSSION:

A.
LIMITATIONS
OF
THE
STUDY:

Major
issues
of
concern
in
evaluation
of
the
study
include:

 
The
baseline
cholinesterase
levels
for
workers
was
established
by
taking
a
sample
3
days
prior
and
another
sample
one
day
prior
to
the
day
where
the
workers
were
exposed
to
AZM
residues
while
performing
postapplication
tasks.
Most
guidelines
recommend
that
baseline
blood
samples
be
taken
at
a
time
when
the
worker
has
not
been
exposed
to
organophosphates
or
n­
methyl
carbamates
for
at
least
30
days.
Workers
in
the
study
stated
that
they
had
not
been
exposed
to
organophosphates
or
n­
methyl
carbamates
for
at
least
10
days
prior
to
the
study,
but
that
could
not
be
independently
verified.
Guidelines
generally
also
recommend
that
establishing
a
stable
baseline
requires
a
minimum
of
two
pre­
exposure
tests
taken
at
least
3
days,
but
not
more
than
14
days,
apart.
Considering
these
factors,
the
baseline
ChE
levels
in
the
study
may
not
reflect
actual
baseline
levels
in
unexposed
workers.
The
baseline
ChE
levels
measured
in
the
study
fall
within
the
normal
range
of
ChE
levels
in
the
blood.

 
Since
the
blood
cholinesterase
data
reflect
a
single
day
of
exposure,
it
would
be
expected
that
successive
days
of
exposure
would
result
in
additional
depression
of
ChE
that
could
be
cumulative.
The
data
do
not
permit
estimating
the
slope
of
recovery
for
ChE
plasma
and
RBC
levels
back
to
normal
levels,
therefore
it
is
difficult
to
predict
the
cumulative
effect
of
successive
days
of
exposure.

This
study
met
most
of
the
Group
B
875.2500
(
inhalation
exposure)
and
875.2600
(
biological
monitoring)
Guidelines.
The
major
issues
of
concern
are:

 
The
guideline
states
that
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;
and
information
on
storage
stability
should
be
provided.
The
Study
Report
states
that
samples
were
stored
frozen
prior
to
analysis
and
that
field
fortification
samples
and
recoveries
were
used
to
demonstrate
storage
stability.
A
separate
storage
stability
study
was
not
mentioned.

 
The
guideline
states
that
data
should
be
corrected
if
any
appropriate
field
fortified,
laboratory
fortified
or
storage
stability
recovery
is
less
than
90
percent.
The
Study
Report
states
that
corrections
were
made
even
if
field
fortification
recoveries
were
above
90%.
Field
samples
were
corrected
for
all
field
fortification
recoveries.
    
16
  
21
 
The
guideline
states
that
for
urine
monitoring,
there
should
also
be
a
sufficient
time
period
between
exposures
to
the
test
substance
or
structurally
related
compounds
and
participation
in
the
study
to
ensure
adequate
urinary
clearance
of
the
compound
and
its
metabolites,
based
on
pharmacokinetic
data.
The
Study
Report
stated
that
workers
were
not
exposed
to
azinphos­
methyl
or
any
other
organophosphate
and
carbamate
chemicals
for
at
least
10
days
prior
to
harvest.
However,
it
should
be
noted
that
MSMB
residues
were
detected
at
or
above
the
LOQ
in
the
background
urine
samples
of
four
workers.

 
The
guideline
states
that
a
trapping
efficiency
test
for
the
monitoring
media
chosen
must
be
documented.
A
trapping
efficiency
test
was
not
reported.
However,
method
validation
data
exhibited
recoveries
of
103­
107%
for
azinphos­
methyl
and
94­
101%
for
azinphosmethyl
oxon.

 
The
guideline
states
that
air
samples
should
also
be
tested
for
breakthrough
to
ensure
that
collected
material
is
not
lost
from
the
medium
during
sampling
and
it
is
recommended
that
at
least
one
test
be
carried
out
where
the
initial
trap
contains
10X
the
highest
amount
of
residue
expected
in
the
field.
A
breakthrough
test
was
not
mentioned
in
the
Study
Report.

 
The
guideline
states
that
the
extraction
efficiency
of
laboratory
fortified
controls
is
considered
acceptable
if
the
lower
limit
of
the
95%
confidence
interval
is
greater
than
75%,
unless
otherwise
specified
by
the
Agency.
At
a
minimum,
the
guideline
states
that
seven
determinations
should
be
made
at
each
fortification
level
to
calculate
the
mean
and
standard
deviation
for
recovery
and
that
the
total
recovery
from
field­
fortified
samples
must
be
greater
than
50%
for
the
study.
One
laboratory
fortified
sample
yielded
recoveries
of
81%
for
azinphos­
methyl
and
102%
for
azinphos­
methyl
oxon.
There
were
3
fortification
samples
at
each
of
2
levels,
with
all
recoveries
greater
than
96%.

 
The
guideline
states
that
if
trapping
media
or
extracts
from
field
samples
are
to
be
stored
after
exposure,
a
stability
test
of
the
compound
of
interest
must
be
documented
and
the
media
must
be
stored
under
the
same
conditions
as
field
samples.
Storage
stability
samples
should
be
extracted
and
analyzed
immediately
before
and
at
appropriate
periods
during
storage
and
the
time
periods
for
storage
should
be
chosen
so
that
the
longest
corresponds
to
the
longest
projected
storage
period
for
field
samples.
There
was
no
information
in
storage
stability
included
in
the
study
report;
however,
field
fortification
samples
were
collected,
stored
and
analyzed
with
the
field
samples.
    
17
  
21
Table
8.
Total
Azinphos­
methyl
Dose
Estimates
by
Task
Shakers
Sweepers
Rakers
Arithmetic
Mean
Geometric
Mean
Standard
Deviation
Arithmetic
Mean
Geometric
Mean
Standard
Deviation
Arithmeti
c
Mean
Geometric
Mean
Standard
Deviation
mg/
kg/
day
0.00019
0.00017
0.0001
0.00034
0.00034
0.000038
0.00089
0.00073
0.0006
NOTE:
Worker
replicates
wore
dust/
mist
respirators
during
all/
most
of
the
exposure
period.
    
18
  
21
Table
9
Azinphos­
methyl
Internal
Doses
in
Workers
Worker
Number
Sampling
Interval
MSMB
excreted
(
µ
g)
Total
MSMB
excreteda
(
µ
g)
%
of
absorbed
dose
excreted
in
urine
after
120
hours
%
AZM
dose
present
as
MSMB
Total
AZM
Doseb
(
µ
g)
Body
weight
(
kg)
Total
AZM
Dosec
(
mg/
kg
BW)

Shakers
0
day
0.1
0.69
83.6
9.2
8.98
77.11
0.00012
1
day
0.219
2
day
0.15
3
day
0.161
1
4
day
0.062g
0
day
0.257
2.09
83.6
9.2
27.1
105.23
0.00026
1
day
1.313
2
day
0.276
3
day
0.142
2
4
day
0.098g
Sweepers
0
day
0.17
2.2
83.6
9.2
28.6
90.72
0.00032
1
day
1.461
2
day
0.287
3
day
0.129
3
4
day
0.153
0
day
0.326
2.51
83.6
9.2
32.7
88.45
0.00037
1
day
1.191
2
day
0.41
3
day
0.476
4
4
day
0.109
Rakers
0
day
0.64
2.83
83.6
9.2
36.8
88.45
0.00042
1
day
1.144
2
day
0.938
3
day
0.106
5
4
day
­
0.146h
0
day
0.543
2.37
83.6
9.2
30.8
56.7
0.00054
1
day
1.012
2
day
0.462
3
day
0.233
6
4
day
0.122
0
day
1.199
7.22
83.6
9.2
93.9
71.67
0.00131
1
day
4.465
2
day
1.158
3
day
0.225
7
4
day
0.173
0
day
1.337
9.12
83.6
9.2
118.6
95.26
0.00124
1
day
4.793
2
day
1.126
3
day
1.457
8
4
day
0.407
0
day
0.49
10.26
83.6
9.2
133.4
58.06
0.0023
1
day
5.253
9
2
day
2.937
    
19
  
21
Table
9
Azinphos­
methyl
Internal
Doses
in
Workers
Worker
Number
Sampling
Interval
MSMB
excreted
(
µ
g)
Total
MSMB
excreteda
(
µ
g)
%
of
absorbed
dose
excreted
in
urine
after
120
hours
%
AZM
dose
present
as
MSMB
Total
AZM
Doseb
(
µ
g)
Body
weight
(
kg)
Total
AZM
Dosec
(
mg/
kg
BW)

3
day
1.225
4
day
0.355
0
day
0.771
8.57
83.6
9.2
111.5
99.79
0.00112
1
day
3.813
2
day
1.595
3
day
1.614
10
4
day
0.782
0
day
0.537
3.29
83.6
9.2
42.8
96.16
0.00045
1
day
1.699
2
day
0.513
3
day
0.38
11
4
day
0.165
0
day
0.768
4.27
83.6
9.2
55.6
88.45
0.00063
1
day
2.014
2
day
0.966
3
day
0.31
12
4
day
0.216
0
day
1.506
9.01
83.6
9.2
117.1
107.96
0.00109
1
day
4.548
2
day
1.264
3
day
1.207
13
4
day
0.486
0
day
0.346
2.23
83.6
9.2
29
78.93
0.00037
1
day
0.721
2
day
0.58
3
day
0.332
14
4
day
0.252
0
day
0.399
1.59
83.6
9.2
20.6
64.86
0.00032
1
day
0.625
2
day
0.355
3
day
0.147
15
4
day
0.060g
NOTE:
Worker
replicates
wore
dust/
mist
respirators
during
all/
most
of
the
exposure
period.
a
Total
MSMB
excreted
(
ug)
=[(
measured
MSMB
(
AZM
equivalents)
ng/
mL
/
field
fortification
recovery
correction
factor)
 
background
residue
(­
1
day
residue)
ng/
mL
x
24
hour
urine
volume
(
mL)]
1
ug/
1000
ng.
This
amount
was
calculated
for
each
day
(
0­
4)
and
then
summed
to
give
a
120
hour
total
residue
estimate.
Field
fortification
recovery
values
used
for
correction:
105.8%
when
residue
<
2.2
ng
96.2
%
when
residue
>
2.2
ng
b
Total
AZM
Dose
(
µ
g)
=
Total
MSMB
excreted
(
µ
g)
*
%
of
absorbed
dose
excreted
in
urine
after
120
hours/
100
*
%
of
total
AZM
dose
represented
by
MSMB/
100
c
Total
AZM
Dose
(
mg/
kg
BW)
=
((
Total
AZM
Dose
(
µ
g))/
1000)
/
Body
Weight
(
kg)
    
20
  
21
Table
11.
Azinphos­
methyl
Inhalation
Exposures
Worker
Type
Worker
No.
Total
Residuea
(
ng)
Air
Conc
(
µ
g/
m3)

1
2942
3.07
2
1324
1.38
Average
2133
2.22
Geo
Mean
2025
2.06
Shaker
St.
Dev.
1145
1.19
3
1606
1.7
4
3786
3.94
Average
2696
2.81
Geo
Mean
2540
2.57
Sweeper
St.
Dev.
1542
1.61
5
5060
5.27
6
3746
3.9
7
14534
15.14
8
16142
16.81
9
10022
10.44
10
9989
10.41
11
8831
9.2
12
5809
6.05
13
7109
7.41
14
4757
4.95
15
4852
5.05
Average
8259
8.6
Geo
Mean
7419
8.08
Raker
St.
Dev.
4120
4.29
a
Total
Residue
is
the
sum
of
the
azinphos­
methyl
and
azinphos­
methyl
oxon
residues
corrected
for
field
fortification
recovery
values
of:.
For
AZM
samples:
94%
when
residue
<
2,250
ng
and
for
AZM
samples:
86%
when
residue
>
2,250
ng
For
AZM
oxon
samples:
97%
when
residue
<
2,250
ng
and
for
AZM
oxon
samples:
88%
when
residue
>
2,250
ng
a
Total
AZM
Residue
is
the
sum
of
the
azinphos­
methyl
and
azinphos­
methyl
oxon
residues
in
both
top
and
bottom
tube
sections.
1/
2
LOD
was
used
in
calculations
for
residues
<
LOD.
Data
were
corrected
for
AZM
and
AZM
oxon
field
fortification
recovery
values
of
96%
and
113%
,
respectively
were
used
when
residues
were
<
2,250
ng.
When
residue
values
were
>
2,250
ng
recovery
values
of
99%
and
101%
were
used
for
AZM
and
AZM
oxon,
respectively.

b
Air
Concentration
(
µ
g/
m3)
=
Total
Residue
(
µ
g)
[(
Flow
Rate
(
2
L/
min)
*
Sampling
Time
(
480
min))
/
1000
L/
m3]
    
21
  
21
Table
12.
Percent
Depression
of
Cholinesterase
Activity
Average
Cholinesterase
Activity
Determined
on
Days
­
1
and
­
3
Cholinesterase
Activity
and
%
Depression
on
Sampling
Day
0
Cholinesterase
Activity
and
%
Depression
on
Sampling
Day
4
Worker
Type
Worker
Number
Plasma
Red
Blood
Cells
Plasma
%
Depressio
n
Red
Blood
Cells
%
Depression
Plasma
%
Depressio
n
Red
Blood
Cells
%
Depression
1
3.8
11.78
3.86
­
2
11.28
4
4.24
­
12
12.19
­
4
2
3.33
11.87
2.71
18
11.52
3
3.21
3
12.05
­
2
Shaker
Average
3.56
11.82
3.29
8
11.4
4
3.73
­
4
12.12
­
3
3
3.69
13.39
3.57
3
12.83
4
3.61
2
13.01
3
4
3.61
8.88
3.54
2
9.06
­
2
3.55
2
8.91
0
Sweeper
Average
3.65
11.13
3.56
3
10.95
1
3.58
2
10.96
1
5
3.73
10.98
3.6
3
11.15
­
2
3.48
7
10.89
1
6
2.81
12.99
2.61
7
12.87
1
2.93
­
4
12.28
5
7
2.76
14.68
2.73
1
14.13
4
3.03
­
10
13.81
6
8
4.69
12.94
4.47
5
13.52
­
5
4.8
­
2
12.94
0
9
3.24
12.87
3.17
2
13.52
­
5
3.19
2
13.17
­
2
10
4.39
15.19
4.08
7
14.61
4
4.06
7
14.59
4
11
3.62
14.56
3.57
1
13.29
9
3.74
­
3
13.91
4
12
2.71
10.32
2.59
4
9.7
6
2.75
­
1
10.31
0
13
3.9
12.93
3.59
8
12.76
1
3.91
0
12.65
2
14
3.82
13.81
3.42
10
14.04
­
2
3.77
1
13.74
1
15
3.85
14.72
3.71
4
14.07
4
3.95
­
3
14
5
Raker
Average
3.59
13.27
3.41
5
12.56
2
3.6
­
1
12.94
2
